Nanofiber polymers as novel sorbents for on-line solid phase extraction in chromatographic system: A comparison with monolithic reversed phase C18 sorbent.

Abstract: A novel application of nanofiber polymers in the wide area of a sample preparation techniques known as solid phase extraction has been studied. We demonstrated application of nanofibers as sorbents for use in a system including on-line extraction coupled with column-switching high performance liquid chromatography. Four types of nanofibers including polyamide 6 with two different surface densities, poly(ε-caprolactone), and polystyrene were tested. We found that three of them were very efficient extraction sorbents sufficiently stable for application in the on-line system. Our results confirmed that the extraction efficiency of the nanofibers depended on the type and chemistry of the spun polymer as well as on the fabrication process of the nanofibrous mats that affected their density, structure, surface density, and mechanical functionality. We also compared performance of all four nanofibers with a conventional monolithic reversed-phase C18 sorbent in terms of extraction efficiency using on-line solid-phase extraction-HPLC system. Polyamide 6 was found to be the best sorbent for lipophilic analytes with a retention and extraction efficiency for the target analytes comparable with that of the C18 monolith.

Háková|Martina|M|
Havlíková|Lucie Chocholoušová|LC|
Chvojka|Jiří|J|
Švec|František|F|
Solich|Petr|P|
Šatínský|Dalibor|D|

Nanofiber polymers
Extraction
Chromatography
On-line SPE
On-line coupling


New recognition of the natural history and growth pattern of hepatic hemangioma in adults.

Abstract:
AIM
Surgical indications for hepatic hemangiomas are still not clearly defined due to limited data on their natural history. This study aimed to investigate the natural history and growth pattern of hepatic hemangiomas in adults.

METHODS
From April 2010 to March 2013, adult patients with hepatic hemangioma who had no prior treatment were enrolled. A routine follow up was performed to observe the natural history of the lesions and their tendency to cause complications.

RESULTS
A total of 236 patients were enrolled in the study. The median size of hemangiomas was 4.5 cm (range, 0.6-19.2). During a median follow-up period of 48 months (range, 3-266), 61.0% patients had hemangiomas that increased in size, 23.7% patients had stable lesions and 8.5% patients had hemangiomas that decreased in size. The peak growth period of hemangiomas was in patients of less than 30 years of age (0.46 ± 0.41 cm/year) and the growth rate decreased significantly after 50 years of age (0.21 ± 0.40 cm/year). Hemangiomas of less than 2 cm had the lowest growth rate (0.16 ± 0.42 cm/year). The peak growth rate of hemangioma size was 8-10 cm (0.80 ± 0.62 cm/year), then decreased rapidly to 0.47 ± 0.91 cm/year while the hemangiomas were of more than 10 cm. Only nine patients had severe symptoms caused by hemangioma. No patients presented with hemangioma-related complications.

CONCLUSION
The majority of hepatic hemangiomas have the tendency to increase in size but rarely cause complications. All the hemangiomas can be safely managed by observation, and surgery is only considered for patients with severe complications.

Jing|Li|L| Liang|Huang|H| Caifeng|Liu|L| Jianjun|Yan|Y| Feng|Xu|X| Mengchao|Wu|W| Yiqun|Yan|Y|

natural history
growth pattern
hepatic hemangioma
surgical indication


Short time effect of a single session of intense whole-body electromyostimulation on energy expenditure. A contribution to fat reduction?

Abstract: To determine the underlying mechanisms after 1 session of (intense) whole-body electromyostimulation (WB-EMS) on total energy expenditure (TEE) and resting metabolic rate (RMR), 16 subjects followed a standardized protocol of indirect calorimetry for up to 72 h in 12-h intervals. The single session significantly increased RMR by approximately 25% ± 10% (p < 0.001) and TEE by approximately 9.5% ± 1%, a net effect of ∼460 ± 50 kcal (WB-EMS vs. control group).

Teschler|Marc|M|
Wassermann|Alfred|A|
Weissenfels|Anja|A|
Fröhlich|Michael|M|
Kohl|Matthias|M|
Bebenek|Michael|M|
von Stengel|Simon|S|
Kemmler|Wolfgang|W|

D000328:Adult
D001481:Basal Metabolism
D001823:Body Composition
D015992:Body Mass Index
D001835:Body Weight
D002153:Calorimetry, Indirect
D018592:Cross-Over Studies
D004558:Electric Stimulation
D004734:Energy Metabolism
D005260:Female
D006801:Humans
D050356:Lipid Metabolism
D008297:Male
D008875:Middle Aged
D018482:Muscle, Skeletal
D055815:Young Adult

whole-body electromyostimulation
fat reduction
WB-EMS
total energy expenditure
resting metabolic rate
RMR
body composition
composition corporelle
diminution des graisses
dépense énergétique totale
métabolisme de repos
électromyostimulation du corps entier


Violence victimization and negative health correlates of youth in post-earthquake Haiti: Findings from the cross-sectional violence against children survey.

Abstract:
BACKGROUND
We examined the prevalence of and relationships between violence victimization and negative health correlates of Haitian youth exposed to the 2010 earthquake.

METHODS
Participants were randomly selected 13-24 year-old youth (1457 females; 1459 males) living in Haiti following the 2010 earthquake. Data collected via Haiti's 2012 Violence against Children Survey (VACS) were analyzed.

RESULTS
Participants reported violence victimization in the past 12 months (females: 49.93%; males: 41.68%), moderate-to-severe mental distress (females: 76.56%; males: 66.41%), and suicidal ideation (females: 26.79%; males: 8.05%). Compared to participants without experiences of violence, victims of violence had significantly higher mean number of sexual partners (females: 1.99, 95% CI: 1.81-2.16, p = .02; males: 4.33, 95% CI: 3.50-5.16, p = .03), mental distress (females: 80.39%, p = .01; males: 72.95%, p = .002), and suicidal ideation (females: 36.09%, p < .0001; males: 12.02%, p < .0001). Male victims of violence were more likely to have sex without a condom (26.02%, p = .01) and female victims of violence were more likely to report histories of STIs (28.04%, p = .01), when compared to participants without history of violence.

LIMITATIONS
Data were collected via self-report. Disaster exposure experiences were not assessed. Analysis was correlational and did not control for potential confounding variables.

CONCLUSIONS
Disaster-exposed youth endorsed high levels of violence victimization and negative health correlates. Earthquake survivors who experienced violence were more likely to report negative health correlates. Greater attention to downstream sequelae of natural disasters is needed.

Lai|Betty S|BS|
Osborne|Melissa C|MC|
De Veauuse-Brown|Natasha|N|
Swedo|Elizabeth A|EA|
Self-Brown|Shannon|S|
Massetti|Greta M|GM|

Violence Youth Children Earthquake Disaster Displacement


Inhabiting the state subjunctively: Transgender life-making alongside death and a pandemic.

Abstract: The Indian Prime Minister, Narendra Modi, while addressing the United Nations General Assembly on 26 September 2020, stated that India had introduced legal reforms to accord rights to transgender citizens. Even though there is not much material basis to these rights, transgender communities have been protesting against the state and at times negotiating with it to get laws that are more in alignment with their rights. In the wake of serialised deaths and precarity intensified by the Covid-19 pandemic, transgender communities also stage other negotiations in the everyday with activists, transnationally funded NGOs and academics researching their communities, encounters that are not as spectacular as the protests against the state, but that which ensures their daily sustenance. This paper investigates how they inhabit these systemically violent institutions. Deploying ethnographic field notes from eastern India, this paper argues that they inhabit them subjunctively, which is not about refusing engagement with what is oppressive but about the ceaseless conjuring of improvisatory and contingent gestures that are marked by hope as well as uncertainty. The simultaneity of protests, rage, hopelessness, hope, negotiations, supplications and scepticism allow them to not only endure the violence of institutions but also to rupture them and imagine them otherwise.

death
Transgender communities
Covid
homonationalism
nation-state


Expression, Purification, and Crystallization of Full-Length HSV-1 gB for Structure Determination.

Abstract: HSV glycoproteins play important roles in the viral life cycle, particularly viral cell entry. Here we describe the protocol for expression, purification, and crystallization of full-length HSV-1 glycoprotein B. The protocol provides a framework for incorporating transmembrane domain-stabilizing amphipols into the crystallization setup and can be adapted to isolate other complete HSV glycoproteins.

Cooper|Rebecca S|RS|
Heldwein|Ekaterina E|EE|

D000818:Animals
D018360:Crystallography, X-Ray
D015870:Gene Expression
D018259:Herpesvirus 1, Human
D000072417:Protein Domains
D011994:Recombinant Proteins
D061987:Sf9 Cells
D018411:Spodoptera
D014759:Viral Envelope Proteins

Glycoproteins
Crystallography
Ectodomain
Herpes simplex viruses
Membrane protein
Protein purification
Viral entry


Up-Regulation of hsa-miR-210 Promotes Venous Metastasis and Predicts Poor Prognosis in Hepatocellular Carcinoma.

Abstract: Objective: To investigate the potential biomarkers for venous metastasis of hepatocellular carcinoma (HCC), and briefly discuss their target genes and the signaling pathways they are involved in. Materials and Method: The dataset GSE6857 was downloaded from GEO. Significantly differentially expressed miRNAs were identified using the R package "limma," After that, the survival analysis was conducted to discover the significance of these up-regulated miRNAs for the prognosis of HCC patients. Additionally, miRNAs which were up-regulated in venous metastasis positive HCC tissues and were significant for the prognosis of HCC patients were further verified in clinical samples using RT-qPCR. The miRNAs were then analyzed for their correlations with clinical characteristics including survival time, AFP level, pathological grade, TNM stage, tumor stage, lymph-node metastasis, distant metastasis, child-pugh score, vascular invasion, liver fibrosis and race using 375 HCC samples downloaded from the TCGA database. The target genes of these miRNAs were obtained using a miRNA target gene prediction database, and their functions were analyzed using the online tool DAVID. Results: 15 miRNAs were differentially expressed in samples with venous metastasis, among which 7 were up-regulated in venous metastasis positive HCC samples. As one of the up-regulated miRNAs, hsa-miR-210 was identified as an independent prognostic factor for HCC. Using RT-qPCR, it was evident that hsa-miR-210 expression was significantly higher in venous metastasis positive HCC samples (p = 0.0036). Further analysis indicated that hsa-miR-210 was positively associated with AFP level, pathological grade, TNM stage, tumor stage and vascular invasion. A total of 168 hsa-miR-210 target genes, which are mainly related to tumor metastasis and tumor signaling pathways, were also predicted in this study. Conclusion: hsa-miR-210 might promote vascular invasion of HCC cells and could be used as a prognostic biomarker.

Ji|Jia|J| Rong|Yuan|Y| Luo|Chang-Liang|CL| Li|Shuo|S| Jiang|Xiang|X| Weng|Hong|H| Chen|Hao|H| Zhang|Wu-Wen|WW| Xie|Wen|W| Wang|Fu-Bing|FB|

hsa-miR-210
venous metastasis
prognosis
hepatocellular carcinoma
RT-qPCR
bioinformatics analysis
public gene database


Intercellular Calcium Signaling Induced by ATP Potentiates Macrophage Phagocytosis.

Abstract: Extracellular ATP is a signaling molecule exploited by the immune cells for both autocrine regulation and paracrine communication. By performing live calcium imaging experiments, we show that triggered mouse macrophages are able to propagate calcium signals to resting bystander cells by releasing ATP. ATP-based intercellular communication is mediated by P2X4 and P2X7 receptors and is a feature of pro-inflammatory macrophages. In terms of functional significance, ATP signaling is required for efficient phagocytosis of pathogen-derived molecules and apoptotic cells and may represent a target for macrophage regulation by CD39-expressing cells. These results highlight a cell-to-cell communication mechanism tuning innate immunity.

Zumerle|Sara|S|
Calì|Bianca|B|
Munari|Fabio|F|
Angioni|Roberta|R|
Di Virgilio|Francesco|F|
Molon|Barbara|B|
Viola|Antonella|A|

calcium
macrophage
phagocytosis
P2X receptors
adenosine triphosphate


Recent advances on anti-HIV vaginal delivery systems development.

Abstract: A review of the recent outcomes regarding technologies to prevent vaginal transmission of HIV, mainly by using antiretroviral (ARV) drugs formulated as microbicides. An introduction about the HIV transmission mechanisms by the vaginal route is included, together with the recent challenges faced for development of successful microbicide products. The outcomes of clinical evaluations are mentioned, and the different formulation strategies studied to-date, with the requirements, advantages, disadvantages and limitations of each dosage-form type, are presented. Finally, the recent attempts to apply various types of nanotechnologies in order to develop advanced microbicide-products and overcome existing limitations, are discussed.

D014622:Vaginal Creams, Foams, and Jellies

Vaginal Transmission HIV Formulation Microbicides Nanotechnology AIDS Mucosal


G Protein-Coupled Estrogen Receptor 30 Reduces Transverse Aortic Constriction-Induced Myocardial Fibrosis in Aged Female Mice by Inhibiting the ERK1/2 -MMP-9 Signaling Pathway.

Abstract: The incidence of cardiovascular diseases was significantly increased in postmenopausal women. The protection of estrogen in the cardiovascular system has been further reported for decades. Although menopausal hormone therapy has been used in many clinical trials, the debatable results indicate that the studies for elucidating the precise molecular mechanism are urgently required. G protein-coupled estrogen receptor 30 (GPR30) is a membrane receptor of estrogen and displays protective roles in diverse cardiovascular diseases. Previous studies have revealed that ERK1/2-mediated MMP-9 signaling was involved in ischemic heart diseases. However, the role of ERK1/2-mediated MMP-9 signaling in the protection of GPR30 against cardiac hypertrophy in aged female mice has not been investigated. Our present study demonstrated that GPR30 overexpression and its agonist G1 co-administration reduced transverse aortic constriction-induced myocardial fibrosis and preserved cardiac function in aged female mice. MMP-9 expression was markedly increased via ERK1/2 phosphorylation in transverse aortic constriction-injured myocardium of aged female mice. Further results showed that GPR30/G1 activation decreased MMP-9 expression via ERK1/2 inhibition, which further reduced TGF-β1 expression. Inhibition of the ERK1/2 signaling pathway by its inhibitor PD98059 suppressed the induction of the cardiomyocyte MMP-9 level caused by the GRP30 antagonist G15 and inhibited TGF-β1 expression in cardiac fibroblast in vitro. In summary, our results from in vivo and in vitro studies indicated that GPR30 activation inhibited myocardial fibrosis and preserved cardiac function via inhibiting ERK-mediated MMP-9 expression. Thus, the present study may provide the novel drug targets for prevention and treatment of cardiac pathological hypertrophy in postmenopausal women.

Wang|Xiaowu|X| Ma|Jipeng|J| Zhang|Shuaishuai|S| Li|Zilin|Z| Hong|Ziwei|Z| Jiang|Liqing|L| Duan|Weixun|W| Liu|Jincheng|J|

G protein–coupled estrogen receptor 30 (GPR30)


Cognitive risk factors explain the relations between neuroticism and social anxiety for males and females.

Abstract: The hierarchical model of vulnerabilities to emotional distress contextualizes the relation between neuroticism and social anxiety as occurring indirectly through cognitive risk factors. In particular, inhibitory intolerance of uncertainty (IU; difficulty in uncertain circumstances), fear of negative evaluation (FNE; fear of being judged negatively), and anxiety sensitivity (AS) social concerns (fear of outwardly observable anxiety) are related to social anxiety. It is unclear whether these risk factors uniquely relate to social anxiety, and whether they account for the relations between neuroticism and social anxiety. The indirect relations between neuroticism and social anxiety through these and other risk factors were examined using structural equation modeling in a sample of 462 individuals (M age = 36.56, SD = 12.93; 64.3% female). Results indicated that the relations between neuroticism and social anxiety could be explained through inhibitory IU, FNE, and AS social concerns. No gender differences were found. These findings provide support for the hierarchical model of vulnerabilities to emotional distress disorders, although the cognitive risk factors accounted for variance beyond their contribution to the relation between neuroticism and social anxiety, suggesting a more complex model than that expressed in the hierarchical model of vulnerabilities.

Allan|Nicholas P|NP|
Oglesby|Mary E|ME|
Uhl|Aubree|A|
Schmidt|Norman B|NB|

neuroticism
Social anxiety
intolerance of uncertainty
fear of negative evaluation
anxiety sensitivity


Adoptive cell transfer in autoimmune hepatitis.

Abstract: Adoptive cell transfer is an intervention in which autologous immune cells that have been expanded ex vivo are re-introduced to mitigate a pathological process. Tregs, mesenchymal stromal cells, dendritic cells, macrophages and myeloid-derived suppressor cells have been transferred in diverse immune-mediated diseases, and Tregs have been the focus of investigations in autoimmune hepatitis. Transferred Tregs have improved histological findings in animal models of autoimmune hepatitis and autoimmune cholangitis. Key challenges relate to discrepant findings among studies, phenotypic instability of the transferred population, uncertain side effects and possible need for staged therapy involving anti-inflammatory drugs. Future investigations must resolve issues about the purification, durability and safety of these cells and consider alternative populations if necessary.

autoimmune hepatitis
Tregs
adoptive transfer
treatment


A hierarchical random additive model for passive scalars in wall-bounded flows at high Reynolds numbers.

Abstract: The kinematics of a fully developed passive scalar is modelled using the hierarchical random additive process (HRAP) formalism. Here, 'a fully developed passive scalar' refers to a scalar field whose instantaneous fluctuations are statistically stationary, and the 'HRAP formalism' is a recently proposed interpretation of the Townsend attached eddy hypothesis. The HRAP model was previously used to model the kinematics of velocity fluctuations in wall turbulence:  , where the instantaneous streamwise velocity fluctuation at a generic wall-normal location z is modelled as a sum of additive contributions from wall-attached eddies (a  ) and the number of addends is N  ~ log(δ/z). The HRAP model admits generalized logarithmic scalings including 〈ϕ 2〉~log(δ/z), 〈ϕ(x)ϕ(x+r  )〉 ~ log(δ/r  ), 〈(ϕ(x) - ϕ(x+r  ))2〉 ~ log(r  /z), where ϕ is the streamwise velocity fluctuation, δ is an outer length scale, r  is the two-point displacement in the streamwise direction and 〈·〉 denotes ensemble averaging. If the statistical behaviours of the streamwise velocity fluctuation and the fluctuation of a passive scalar are similar, we can expect first that the above mentioned scalings also exist for passive scalars (i.e. for ϕ being fluctuations of scalar concentration) and second that the instantaneous fluctuations of a passive scalar can be modelled using the HRAP model as well. Such expectations are confirmed using large-eddy simulations. Hence the work here presents a framework for modelling scalar turbulence in high Reynolds number wall-bounded flows.

turbulence theory
turbulent boundary layers
turbulent flows


A mutation in the Arabidopsis thaliana cell wall biosynthesis gene pectin methylesterase 3 as well as its aberrant expression cause hypersensitivity specifically to Zn.

Abstract: Defects in metal homeostasis factors are often accompanied by the loss of metal tolerance. Therefore, we screened for mutants with compromised growth in the presence of excess Zn(2+) in order to identify factors involved in Zn biology in plants. Here we report the isolation of six ozs (overly Zn sensitive) ethyl methanesulfonate Arabidopsis thaliana mutants with contrasting patterns of metal sensitivity, and the molecular characterization of two mutants hypersensitive specifically to Zn(2+) . Mutant ozs1 represents a non-functional allele of the vacuolar Zn transporter AtMTP1, providing additional genetic evidence for its major role in Zn(2+) tolerance in seedlings. Mutant ozs2 carries a semi-dominant mutation in the gene encoding pectin methylesterase 3 (AtPME3), an enzyme catalyzing demethylesterification of pectin. The mutation results in impaired proteolytic processing of AtPME3. Ectopic expression of AtPME3 causes strong Zn(2+) hypersensitivity that is tightly correlated with transcript abundance. Together these observations suggest detrimental effects on Golgi-localized processes. The ozs2 but not the ozs1 phenotype can be suppressed by extra Ca(2+) , indicating changes in apoplastic cation-binding capacity. However, we did not detect any changes in bulk metal-binding capacity, overall pectin methylesterification status or cell wall ultrastructure in ozs2, leading us to hypothesize that the ozs2 mutation causes hypersensitivity towards the specific interference of Zn ions with cell wall-controlled growth processes.

Weber|Michael|M| Deinlein|Ulrich|U| Fischer|Sina|S| Rogowski|Michaela|M| Geimer|Stefan|S| Tenhaken|Raimund|R| Clemens|Stephan|S|

D018506:Gene Expression Regulation, Plant

Arabidopsis thaliana
cell wall
pectin
metal homeostasis
metal tolerance
Zn homeostasis
Zn tolerance


Ankyloblepharon-ectodermal dysplasia-clefting syndrome misdiagnosed as epidermolysis bullosa and congenital ichthyosiform erythroderma: Case report and review of published work.

Abstract: A Chinese female infant presented with ectodermal dysplasia, cleft palate and severe skin erosions at birth. Although all the typical clinical features of ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome were present, the ankyloblepharon was not very marked. We misdiagnosed epidermolysis bullosa and congenital ichthyosiform erythroderma at first and confirmed the diagnosis of AEC syndrome only when she presented with the typical clinical manifestation of recurrent infected scalp erosions at 1 year of age. Mutation analysis of exon 13 of the p63 gene revealed a missense mutation Ile482Thr (c.1445T>C) in the sterile alpha motive domain. In this work we review the clinical features, differential diagnosis and prognosis in AEC syndrome.


Sudden unexpected death in Parkinson's disease: why is drinking water important?

Abstract: Parkinson's disease (PD) is one of the most common age-related neurodegenerative disorders. Several studies over the last few years have shown that PD is accompanied by high rates of premature death compared with healthy controls. Death in PD patients is usually caused by determinant factors such as pneumonia, and cerebrovascular and cardiovascular diseases. During recent years it has emerged that dehydration may also contribute to mortality in PD. Interestingly, it has been documented that a substantial proportion of patients with PD die suddenly (known as sudden and unexpected death in PD). In this article, we focus on the magnitude of the problem of sudden and unexpected death in PD, with special reference to the daily water consumption of PD patients.

Menezes-Rodrigues|Francisco S|FS|
Scorza|Cristiane S|CS|
Fiorini|Ana C|AC|
Caricati-Neto|Afonso|A|
Scorza|Carla A|CA|
Finsterer|Josef|J|
Scorza|Fulvio A|FA|

D000978:Antiparkinson Agents
D003645:Death, Sudden
D003680:Deglutition Disorders
D003681:Dehydration
D004327:Drinking Behavior
D005440:Fluid Therapy
D006801:Humans
D009459:Neuroleptic Malignant Syndrome
D010300:Parkinson Disease
D010349:Patient Compliance
D014867:Water
D014882:Water-Electrolyte Balance
D014883:Water-Electrolyte Imbalance

dehydration
water consumption
Parkinson’s disease
elderly
sudden death


Sequential Steps of CRAC Channel Activation.

Abstract: Interaction between the endoplasmic reticulum protein STIM1 and the plasma membrane channel ORAI1 generates calcium signals that are central for diverse cellular functions. How STIM1 binds and activates ORAI1 remains poorly understood. Using electrophysiological, optical, and biochemical techniques, we examined the effects of mutations in the STIM1-ORAI1 activating region (SOAR) of STIM1. We find that SOAR mutants that are deficient in binding to resting ORAI1 channels are able to bind to and boost activation of partially activated ORAI1 channels. We further show that the STIM1 binding regions on ORAI1 undergo structural rearrangement during channel activation. The results suggest that activation of ORAI1 by SOAR occurs in multiple steps. In the first step, SOAR binds to ORAI1, partially activates the channel, and induces a rearrangement in the SOAR-binding site of ORAI1. That rearrangement of ORAI1 then permits sequential steps of SOAR binding, via distinct molecular interactions, to fully activate the channel.

Palty|Raz|R|
Fu|Zhu|Z|
Isacoff|Ehud Y|EY|

D000071737:Stromal Interaction Molecule 1


Data on multimerization efficiency for short linear DNA templates and phosphoryl guanidine primers during isothermal amplification with Bst exo- DNA polymerase.

Abstract: This article reports experimental data related to the research article entitled "Prevention of DNA multimerization using phosphoryl guanidine primers during isothermal amplification with Bst exo- DNA polymerase" (R.R. Garafutdinov, A.R. Sakhabutdinova, M.S. Kupryushkin, D.V. Pyshnyi, 2020) [1]. Here, multimerization efficiency in terms of Tt (time-to-threshold) values obtained for artificial DNA templates with the different nucleotide sequences during isothermal amplification with Bst exo- DNA polymerase is given. Data on the influence of phosphoryl guanidine primers (PGO) on multimerization for the LTc template which has shown high efficiency of multimerization are presented as well.

Garafutdinov|Ravil R|RR|
Sakhabutdinova|Assol R|AR|
Kupryushkin|Maxim S|MS|
Pyshnyi|Dmitrii V|DV|

Phosphoryl guanidine oligonucleotides (PGO)


A Convenient, Rapid, Sensitive, and Reliable Spectrophotometric Assay for Adenylate Kinase Activity.

Abstract: Enzymatic activity assays are essential and critical for the study of enzyme kinetics. Adenylate kinase (Adk) plays a fundamental role in cellular energy and nucleotide homeostasis. To date, assays based on different principles have been used for the determination of Adk activity. Here, we show a spectrophotometric analysis technique to determine Adk activity with bromothymol blue as a pH indicator. We analyzed the effects of substrates and the pH indicator on the assay using orthogonal design and then established the most optimal assay for Adk activity. Subsequently, we evaluated the thermostability of Adk and the inhibitory effect of KCl on Adk activity with this assay. Our results show that this assay is simple, rapid, and precise. It shows great potential as an alternative to the conventional Adk activity assay. Our results also suggest that orthogonal design is an effective approach, which is very suitable for the optimization of complex enzyme reaction conditions.

Song|Kai|K| Wang|Yejing|Y| Li|Yu|Y| Ding|Chaoxiang|C| Cai|Rui|R| Tao|Gang|G| Zhao|Ping|P| Xia|Qingyou|Q|0000-0002-9263-2886 He|Huawei|H|0000-0002-3805-8940

adenylate kinase
enzymatic activity assay
bromothymol blue
orthogonal experiment
spectrophotometry


Dietary Linseed Oil Reduces Growth While Differentially Impacting LC-PUFA Synthesis and Accretion into Tissues in Eurasian Perch (Perca fluviatilis).

Abstract: The aim of this study was to evaluate the impact of replacing dietary fish oil (FO) with linseed oil (LO) on growth, fatty acid composition and regulation of lipid metabolism in Eurasian perch (Perca fluviatilis) juveniles. Fish (17.5 g initial body weight) were fed isoproteic and isoenergetic diets containing 116 g/kg of lipid for 10 weeks. Fish fed the LO diet displayed lower growth rates and lower levels of DHA in the liver and muscle than fish fed the FO diet, while mortality was not affected by dietary treatment. However, DHA content recorded in the liver and muscle of fish fed the LO diet remained relatively high, despite a weight gain of 134 % and a reduced dietary level of long-chain polyunsaturated fatty acids (LC-PUFA), suggesting endogenous LC-PUFA biosynthesis. This was supported by the higher amounts of pathway intermediates, including 18:4n-3, 20:3n-3, 20:4n-3, 18:3n-6 and 20:3n-6, recorded in the liver of fish fed the LO diet in comparison with those fed the FO diet. However, fads2 and elovl5 gene expression and FADS2 enzyme activity were comparable between the two groups. Similarly, the expression of genes involved in eicosanoid synthesis was not modulated by dietary LO. Thus, the present study demonstrated that in fish fed LO for 10 weeks, growth was reduced but DHA levels in tissues were largely maintained compared to fish fed FO, suggesting a physiologically relevant rate of endogenous LC-PUFA biosynthesis capacity.

Geay|F|F|
Wenon|D|D|
Mellery|J|J|
Tinti|E|E|
Mandiki|S N M|SN|
Tocher|D R|DR|
Debier|C|C|
Larondelle|Y|Y|
Kestemont|P|P|

D018507:Gene Expression Regulation, Developmental

LC-PUFA
Eurasian perch
FADS2
Eicosanoid
Fatty acid metabolism


Editorial.

Abstract: no summary.

Dudek|Dominika|D|
Sobański|Jerzy A|JA|
Klasa|Katarzyna|K|


Burnout in gastroenterology registrars: a feasibility study conducted in the East of England using a 31-item questionnaire.

Abstract:
OBJECTIVE
The scale of burnout in UK gastroenterology trainees and the feasibility to determine its prevalence using the validated Maslach Burnout Inventory-Human Services Survey (MBI-HSS) tool are unknown. The primary objective of this region-wide pilot study was to evaluate the response rate to a 31-item questionnaire. The secondary objectives were to estimate the prevalence of burnout in gastroenterology trainees within the East of England deanery (EoE) and identify common stressors that trainees experience.

DESIGN
This was a cross-sectional study involving gastroenterology trainees from 16 hospitals across the EoE using a 31-item questionnaire. The questionnaire consisted of the 22-item MBI-HSS and nine additional free-text questions. All gastroenterology trainees in the EoE were invited to complete the anonymised survey online. Data were analysed quantitatively and qualitatively.

RESULTS
The response rate for the survey was acceptable: 44.0% (40/91). 57.5% (23/40) of gastroenterology trainees reported emotional exhaustion. 23.5% (8/34) had depersonalisation and 63.9% (23/36) experienced low professional accomplishment. Burnout prevalence was 35.3% (12/34). 48.4% (15/31) of gastroenterology trainees were aware of professional support services within EoE. Stressors related to service requirements (eg, workload, staffing levels) and professional relationships with colleagues and patients were commonly reported: 65.6% and 25.0%, respectively.

CONCLUSIONS
It is feasible to use a 31-item questionnaire in a national cohort of UK gastroenterology trainees for future burnout studies. Burnout in EoE gastroenterology trainees was high and this may reflect a national prevalence within the specialty. More extensive studies, greater awareness of burnout and improved access to professional support services are required.

health service research
psychological stress
psychology
quality of life
screening


Performance of nitrogen removal in an alternating activated sludge reactor for full-scale applications.

Abstract: A novel wastewater treatment process, known as an alternating activated sludge reactor (AASR), is proposed to treat wastewater in full-scale operations. The AASR is a technical development based on the sequencing batch reactor (SBR) and cyclic activated sludge technology (CAST). The performance of AASR was evaluated in this study and found to be effective for the removal of pollutants. The average effluent NH4+-N, TN, TP, and COD concentrations were 0.5, 17, 0.8, and 40 mgL-1, respectively. The corresponding average removal efficiencies were 97%, 59%, 83%, and 83%, respectively, indicating that the AASR was also a successful operating system for the removal of organic matter. The AASR has many advantages, such as successive filling, high removal efficiency, high stability and reliability, low area requirement, no sludge circulation reflux, and low construction costs. The operation mode of the alternating anoxic, anaerobic, and aerobic conditions displayed a higher efficiency for nitrification than that of conventional SBR. The effective mode for denitrification was a step-feed. The control program of the AASR is highly flexible and can easily be modified by a plant manager to meet various loading requirements.


Pancreatic hamartoma in a premature Trisomy 18 female.

Abstract: Pancreatic hamartomas are extremely rare tumors in adults and even more so in children. They are lesions characterized by acinar, islet and ductal components found in varying proportions and in a disorganized pattern. We report a case of a premature female with trisomy 18 diagnosed by amniocentesis. The newborn was delivered by cesarean section at thirty-three weeks of gestation and expired within one hour of birth. Postmortem examination exhibited numerous features associated with Trisomy 18 including lanugo on the torso and arms, micrognathia, microstomia, left low-set ear with small flat pinna, closed ear canal, clenched fists with overlapping fingers, rocker-bottom feet, narrow pelvis, large right diaphragmatic hernia and left pulmonary hypoplasia. Microscopic examination of the pancreas revealed an area, 1.2 cm in greatest dimension, with branching ducts and cysts lined by cuboidal epithelium intermingled within primitive mesenchymal proliferation and exocrine glands. The cysts measured up to 0.2 cm and were surrounded by a collarette of proliferating spindle cells as highlighted by Masson's trichrome stain. A diagnosis of pancreatic hamartoma was rendered. A total of thirty-four cases of pancreatic hamartomas have been reported in the literature including twenty-seven in adults, five in children and two in newborns. Our case may be the third pancreatic hamartoma reported in association with Trisomy 18. We recommend that careful examination of the pancreas be performed in individuals with Trisomy 18 to further characterize this lesion as one of the possible abnormal findings associated with this syndrome.

Delgado|Patricia Isabel|PI|
Correa-Medina|Mayrin|M|
Rojas|Claudia P|CP|

hamartoma
Trisomy 18
pancreas
Edwards Syndrome
pancreatic neoplasm


Does T Helper Differentiation Correlate with Resistance or Susceptibility to Infection with L. major? Some Insights From the Murine Model.

Abstract: The murine model of Leishmania major infection has been an invaluable tool in understanding T helper differentiation in vivo. The initial evidence for a role of distinct CD4(+) T helper subsets in the outcome of infection was first obtained with this experimental model. The development of CD4(+) Th1 cells was associated with resolution of the lesion, control of parasite replication, and resistance to re-infection in most of the mouse strains investigated (i.e., C57BL/6). In contrast, differentiation of CD4(+) Th2 cells correlated with the development of unhealing lesions, and failure to control parasite load in a few strains (i.e., BALB/c). Since these first reports, an incredible amount of effort has been devoted to understanding the various parameters involved in the differentiation of these, and more recently discovered T helper subsets such as Th17 and T regulatory cells. The discovery of cross-talk between T helper subsets, as well as their plasticity force us to reevaluate the events driving a protective/deleterious T helper immune response following infection with L. major in mice. In this review, we describe the individual contributions of each of these CD4(+) T helper subsets following L. major inoculation, emphasizing recent advances in the field, such as the impact of different substrains of L. major on the pathogenesis of disease.


Exposure to teasing on popular television shows and associations with adolescent body satisfaction.

Abstract:
OBJECTIVE
This study uses a novel mixed methods design to examine the relationship between incidents of teasing in popular television shows and body satisfaction of adolescent viewers.

METHODS
Survey data were used to identify 25 favorite television shows in a large population-based sample of Minnesota adolescents (N=2793, age=14.4years). Data from content analysis of teasing incidents in popular shows were linked to adolescent survey data. Linear regression models examined associations between exposure to on-screen teasing in adolescents' own favorite shows and their body satisfaction. Effect modification by adolescent weight status was tested using interaction terms.

RESULTS
Teasing on TV was common, with 3.3 incidents per episode; over one-quarter of teasing was weight/shape-related. Exposure to weight/shape-related teasing (β=-0.43, p=0.008) and teasing with overweight targets (β=-0.03, p=0.02) was inversely associated with girls' body satisfaction; no associations were found for boys. Findings were similar regardless of the adolescent viewer's weight status.

CONCLUSIONS
Families, health care providers, media literacy programs and the entertainment industry are encouraged to consider the negative effects exposure to weight stigmatization can have on adolescent girls.

Eisenberg|Marla E|ME|
Ward|Ellen|E|
Linde|Jennifer A|JA|
Gollust|Sarah E|SE|
Neumark-Sztainer|Dianne|D|

Body satisfaction
Media
Social influence
Weight stigma


Synergistic effect of vascular endothelial growth factor gene inactivation in endothelial cells and skeletal myofibres on muscle enzyme activity, capillary supply and endurance exercise in mice.

Abstract:
NEW FINDINGS
What is the central question of this study? Does vascular endothelial growth factor (VEGF) expressed by both endothelial cells and skeletal myofibres maintain the number of skeletal muscle capillaries and regulate endurance exercise? What is the main finding and its importance? VEGF expressed by both endothelial cells and skeletal myofibres is not essential for maintaining capillary number but does contribute to exercise performance.

ABSTRACT
Many chronic diseases lead to exercise intolerance, with loss of skeletal muscle capillaries. While many muscle cell types (myofibres, satellite cells, endothelial cells, macrophages and fibroblasts) express vascular endothelial growth factor (VEGF), most muscle VEGF is stored in myofibre vesicles which can release VEGF to signal VEGF receptor-expressing cells. VEGF gene ablation in myofibres or endothelial cells alone does not cause capillary regression. We hypothesized that simultaneously deleting the endothelial cell (EC) and skeletal myofibre (Skm) VEGF gene would cause capillary regression and impair exercise performance. This was tested in adult mice by simultaneous conditional deletion of the VEGF gene (Skm/EC-VEGF-/- mice) through the use of VEGFLoxP, HSA-Cre-ERT2 and PDGFb-iCre-ERT2 transgenes. These double-deletion mice were compared to three control groups - WT, EC VEGF gene deletion alone and myofibre VEGF gene deletion alone. Three weeks after initiating gene deletion, Skm/EC-VEGF-/- mice, but not SkmVEGF-/- or EC-VEGF-/- mice, reached exhaustion 40 min sooner than WT mice in treadmill tests (P = 0.002). WT, SkmVEGF-/- and EC-VEGF-/- , but not Skm/EC-VEGF-/- , mice gained weight over the 3 weeks. Capillary density, fibre area and capillary: fibre ratio in soleus, plantaris, gastrocnemius and cardiac papillary muscle were similar across the groups. Phosphofructokinase and pyruvate dehydrogenase activities increased only in Skm/EC-VEGF-/- mice. These data suggest that deletion of the VEGF gene simultaneously in endothelial cells and myofibres, while reducing treadmill endurance and despite compensatory augmentation of glycolysis, is not required for muscle capillary maintenance. Reduced endurance remains unexplained, but may possibly be related to a role for VEGF in controlling perfusion of contracting muscle.

Sulaeman|Alexis|A|
Fine|Janelle|J|
de Vargas-Machuca|Aleix|A|
Vitorino|Steven A|SA|
Wagner|Peter D|PD|
Fruttiger|Marcus|M|
Breen|Ellen C|EC|0000-0003-1962-5353

D042442:Vascular Endothelial Growth Factors

exercise
angiogenesis
peripheral vascular disease


Optimization of reduced chemical fertilizer use in tea gardens based on the assessment of related environmental and economic benefits.

Abstract: Chemical fertilizer application is the primary method used to maintain tea yield and quality, but has a negative environmental impact owing to its excessive use. This study sought to assess the environmental and economic benefits of three different chemical fertilizer reduction modes: Single reduction of chemical fertilizer (SRCF), combined application of organic and chemical fertilizer (CAOF), and controlled-release fertilizer substitute (CRFS). Differences in soil nutrient content, NP (NH4+-N, NO3-N and total P) runoff loss, tea yield and quality, and the revenue of tea planting across different fertilizer reduction treatments were then discussed. We also analyzed the coupling effects of these different fertilization modes, fertilization rate and time on soil NP runoff loss, which allowed us to determine the optimum fertilization method based on differences in their respective environmental and economic benefits. Our results revealed differences in soil nutrient content, tea yield and quality, NP runoff loss, and revenue owing to tea planting across the different fertilization treatments. Soil pH after fertilization was significantly lower than before fertilization. CAOF was beneficial and improved soil nutrients as well as tea yield and quality. Of the tested methods, 50% combined application of organic and chemical fertilizer (CAOF2) was the best, as it resulted in the best tea quality and yield. CAOF2 also had the highest revenue. In addition, it was beneficial in reducing NP runoff loss. CRFS was advantageous in its persistent fertilizer efficiency and reduction in NP runoff loss. With CAOF, NP runoff loss was primarily caused by quick-acting chemical fertilizer. With extended time, NP runoff loss caused by fertilization was gradually decreased. Given our analysis of the environmental and economic benefits of different fertilizer reduction methods, CAOF2 emerged in this study as the best fertilizer reduction treatment option.

Tea garden
Tea yield and quality
Chemical fertilizer reduction
Soil nutrients content
Revenue
NP runoff loss


Protective effects of appropriate Zn(2+) levels against UVB radiation-induced damage in human lens epithelial cells in vitro.

Abstract: As one of the crucial factors of cataract formation, ultraviolet B (UVB) can lead to apoptosis of human lens epithelial cells. Zinc, a cell-protective metal against various toxic compounds, plays an important role in protecting target cells from damage. Nevertheless, it is still unclear whether zinc exhibits protective effect on human lens epithelial cells (HLE B-3) against UVB-induced damage. In this study, we investigated the protective effect of zinc chloride (ZnCl2) on UVB-induced HLE B-3 cell damage, explored the molecular mechanisms using real-time cell electronic sensing system, flow cytometry, real-time quantitative PCR and enzyme-linked immunosorbent assay techniques. The results show that ZnCl2 is a potential inhibitor of UVB-induced HLE B-3 cell damage, and the underlying mechanisms are involved in decreasing the overproduction of reactive oxygen species and mitochondrial dysfunction, promoting intracellular calcium homeostasis recovery, and thus maintaining cell normal physiological functions. Taken together, our findings suggest that appropriate zinc levels have potential for protecting HLE B-3 cells against UVB-induced damage, and this finding may be clinically useful.

Du|Yuxiang|Y| Guo|Dadong|D| Wu|Qiuxin|Q| Shi|Jing|J| Liu|Dongmei|D| Bi|Hongsheng|H|

Sarcoplasmic endoplasmic reticulum calcium ATPase


Loeys-Dietz syndrome and isolated severe ostial left main coronary stenosis presenting as ventricular fibrillation arrest and biventricular takotsubo syndrome in a 25-year-old patient.

Abstract: We present the case of a previously healthy 25-year-old woman who presented with an out-of-hospital ventricular fibrillation arrest. Postresuscitation ECG did not show any evidence of ST segment elevation. Echocardiogram showed regional wall abnormalities in keeping with takotsubo syndrome (TTS). Urgent coronary angiogram to rule out malignant congenital coronary artery anomaly revealed an isolated severe ostial left main coronary artery (LMCA) stenosis, a rare disease, approximately 0.2% in previous case series. The LMCA was aneurysmal. Genetic studies revealed a novel frameshift pathogenic variant in the transforming growth factor B two ligand gene (TGFB2) gene, suggestive of Loeys-Dietz syndrome (LDS) type 4, an aggressive vascular disease. Ostial LMCA stenosis has not been previously reported in LDS, and we outline the management of this unique disease combination. We also reflect on its presentation as TTS and infer that TTS and acute coronary syndromes are not mutually exclusive.

Gargoum|Ahmed|A| Bare|Idris|I| Pekrul|Christopher|C| Nosib|Shravan|S|

arrhythmias
heart failure
interventional cardiology
ischaemic heart disease


Shuyu capsules relieve liver-qi depression by regulating ERK-CREB-BDNF signal pathway in central nervous system of rat.

Abstract: The purpose of this study was to investigate the possible therapeutic mechanism of Shuyu capsules in liver-qi depression. Liver-qi depression rats were prepared based on chronic unpredictable mild stress (CUMS) and delayed constraint. Rats were gavaged with Shuyu capsule, fluoxetine, Radix Bupleuri and Radix Paeoniae Alba to constrct rat models. Body weight test, sucrose preference test and open-field test were applied to test rat models. Western blot analysis and quantitative real-time PCR was applied to determine the relative expression of extracellular signal-regulated protein kinase (ERK), cyclic AMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in hippocampus and frontal lobe tissues. ELISA was used to detect the content of BDNF in serum. Body weight, sugar intake and total distance were significantly decreased in depression group compared with control. The four drugs significantly increased levels of these factors. Compared with control group, ERK, CREB and BDNF expression were significantly decreased in depression group in both hippocampus and frontal lobe tissues at both mRNA and protein level. Shuyu capsule and fluoxetine group showed a significant increase in the expression of ERK, CREB and BDNF at mRNA, p-ERK and p-BDNF at protein level. Compared with Radix Paeoniae Alba, Radix Bupleuri were better in the rescue of ERK, CREB and BDNF expression. In conclusion, the pathogenesis of liver-qi depression associated with lower expression of ERK, CREB and BDNF in hippocampus and frontal. Shuyu capsule and main constitution alleviated the depressive-like behaviors and reversed the disruptions of the p-ERK, p-CREB and BDNF in stressed rats.

Wang|Hongyan|H| Zhang|Yingquan|Y| Li|Helou|H| Zeng|Wei|W| Qiao|Mingqi|M|

Shuyu capsules
depression
ERK-CREB-BDNF signal pathway


Seroprevalence and Risk Factors Associated with Chlamydia abortus Infection in Sheep and Goats in Eastern Saudi Arabia.

Abstract: Chlamydia abortus (C. abortus) is intracellular, Gram-negative bacterium that cause enzootic abortion in sheep and goats. Information on C. abortus seroprevalence and flock management risk factors associated with C. abortus seropositivity in sheep and goats in Saudi Arabia are scarce. The objectives of this study were to (i) estimate the animal, flock, and within-flock seroprevalence of C. abortus among Eastern Province sheep and goat flocks and (ii) identify the flock management and animal risk factors associated with C. abortus seropositivity in Eastern Province, Saudi Arabia. A cross-sectional study with a two-stage sampling process was carried out in the Eastern Province, Saudi Arabia, between 2015 and 2016. A total of 1717 sheep and 1101 goat serum samples were collected from 21 sheep and 14 goat flocks, then were tested for C. abortus antibodies using a commercial ELISA Kit. In addition, vaginal swabs and aborted tissue samples were collected from sheep (n = 48) and goats (n = 15) with recent history of abortion for detection of C. abortuspmp gene using PCR. A questionnaire was constructed to collect information about flock management and animal risk factors possibly associated with C. abortus infection in sheep and goats. The true sheep and goat-level seroprevalences were 11.1% (95% CI: 9.7-12.7) and 10.6% (95% CI: 8.8-12.5), respectively. The true flock-level seroprevalence was 100% for both sheep and goats. However, the average within sheep and goat flocks true seroprevalences were 9.6% (95% CI: 1.8-22.9) and 9.3% (95% CI: 1.8-19.5), respectively. Multivariable logistic regression revealed that introduction of new sheep to the flocks (OR = 2.6; 95% CI: 1.5-4.4), type of breeding system (OR = 1.8; 95% CI: 1.0-3.4), flocks allowing females in (OR = 1.9; 95% CI: 1.1-3.3) or females out (OR = 2.2; 95% CI: 1.1-4.3), and sheep age 1.4-2.8 years (OR = 1.9; 95% CI: 1.3-2.9) were potential risk factors for C. abortus seropositivity in sheep flocks. However, in goat flocks, the introduction of new goats to the flocks (OR: 1.9; 95% CI: 1.2-3.0) was identified as a risk factor, whereas good farm hygiene (OR: 0.3; 95% CI: 0.2-0.7) was identified as a protective factor. C. abortus pmp gene was identified in 45 (93.8%) and 15 (100%) of samples collected from sheep and goats, respectively. These results could be used to implement efficient management measures to prevent and control C. abortus infection in sheep and goats in Eastern Province, Saudi Arabia, but also could be used to reduce the risk of C. abortus infection in sheep and goat flocks with similar management practices in other regions.

seroprevalence
risk factors
Chlamydia abortus
sheep
goats
Saudi Arabia
multivariable analysis


Chemical Composition and Antioxidant Activity of Propolis Prepared in Different Forms and in Different Solvents Useful for Finished Products.

Abstract: Different products from a unique propolis extract obtained by using various solvents such as hydroalcoholic, glycolic (98% propylene glycol), and glyceric solutions, and oil, as well as in powder form, named ESIT12, were prepared. The molecular composition of the different preparations was evaluated and their antioxidant activity determined. All the preparations showed a quite similar polyphenol composition and comparable percentage even if ESIT12 was found to be richer in phenolic acids (caffeic, coumaric, ferulic, and isoferulic). Overall, flavones and flavonols ranged from ~20% up to ~36% in the glyceric extract, while flavanones and diidroflavonols were between ~28% and ~41%. Besides their quite similar composition, glycolic and hydroalcoholic extracts were found to be richer in the total polyphenols content. When the antioxidant properties were determined for the four preparations, the activity was similar among them, thus revealing that it is strictly related to the polyphenols content for propolis products whose composition is quite comparable. To date, very few data are available on propolis composition in glyceric and glycolic extracts and information has never been published on propolis in oil. This study could be of interest to the food and nutraceutical industries to choose suitable solvents and conditions to produce propolis preparations useful for active finished products.

Galeotti|Fabio|F| Maccari|Francesca|F| Fachini|Alfredo|A| Volpi|Nicola|N|0000-0002-0749-6104

propolis
polyphenols
phenolic acids
European brown poplar propolis
flavonoids


Long non-coding RNA LINC00662 promotes proliferation and migration in oral squamous cell carcinoma.

Abstract:
Background
Although increasing evidence has demonstrated important roles for long non-coding RNAs (lncRNAs) in cancer development, their functions in oral squamous cell carcinoma (OSCC) growth remain largely unknown. Therefore, we aimed to investigate the role of LINC00662 in OSCC.

Methods
The expression of LINC00662 in 61 OSCC tissues and four OSCC cell lines were detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell proliferation was detected using Cell Counting Kit-8 (CCK-8) and EdU staining methods. Migration and invasion abilities were analyzed using transwell and wound healing assay. Cell cycle distribution and apoptosis rate were evaluated by flow cytometry. Western blot method was performed to detect protein expression.

Results
We found that the expression of LINC00662 was significantly increased in OSCC tissues, and a higher expression of LINC00662 was detected in larger tumor size, higher stage tumors and with lymph node metastasis. Moreover, overexpression of LINC00662 induced OSCC cell proliferation, increased migration and invasion abilities, and suppressed cell apoptosis. Knockdown of LINC00662 decreased the proliferation, migration, and invasion abilities of OSCC cell, and induced apoptosis. Furthermore, LINC00662 regulated the Wnt/β-catenin pathway.

Conclusion
Our data indicate that LINC00662 may represent a novel indicator of OSCC and may be a potential therapeutic target for diagnosis and therapy.

Xu|Debin|D| Chen|Yunmei|Y| Yuan|Chunlei|C| Zhang|Shuyong|S| Peng|Wei|W|

LINC00662
proliferation
migration
OSCC
Wnt/β-catenin pathway


Water-lifting aerator reduces algal growth in stratified drinking water reservoir: Novel insights into algal metabolic profiling and engineering applications.

Abstract: Water-lifting aerator (WLA) which was developed by Professor Tinglin Huang at Xi'an University of Architecture and Technology, China has multi-functional water quality improvement that significantly inhibits the occurrence of harmful algal blooms (HABs) in deep drinking water reservoirs. However, the biological mechanism of WLA to the suppress algal growth has not been comprehensively understood. Here, the cellular mechanism that allows WLA to control HABs was explored based on the combination of both laboratory simulation and field investigation. Under simulated hydrodynamic conditions, the results showed that the cell density, chlorophyll a content, chlorophyll fluorescence parameters, and dehydrogenase activity in Microcystis aeruginosa all peaked under light conditions at 25 °C. The metabolic activity of M. aeruginosa varied significantly under low temperature at 6 °C and light conditions when cultured for 48 h. The extracellular organic matter (EOM) and intracellular organic matter (IOM) contents of M. aeruginosa were both resolved into three components. Moreover, the total fluorescence intensities from EOM and IOM both peaked under light conditions at 25 °C. The field investigation showed that the growth of algae was decreased significantly in Lijiahe drinking water reservoir with WLA application. The chlorophyll fluorescence parameters decreased significantly after vertical mixing, thereby indicating that the WLA weakened the photosynthetic ability and reduced the biological activity of algae in situ. In addition, the WLA significantly affected the vertical distribution of the phytoplankton community composition. Altogether, these results shed new lights on understanding the control of algal blooms by WLA in stratified drinking water reservoirs. WLA has broad prospect of engineering applications, which can control algal blooms of water supply resources in situ, therefore, reduce the content of disinfection by-products in drinking water treatment plants.

Zhang|Haihan|H| Yan|Miaomiao|M| Huang|Tinglin|T| Huang|Xin|X| Yang|Shangye|S| Li|Nan|N| Wang|Na|N|

Drinking water reservoir
Water-lifting aerator (WLA)
Harmful algal blooms
Chlorophyll fluorescence parameter
Artificial mixing


Standards of care for procedural sedation: Focus on differing perceptions among societies.

Abstract: Adherence to established standards of care is important for anaesthesiologists to avoid undesirable legal consequences of their actions. The judiciary lays stress on the need to perpetuate healthy doctor-patient correspondence, good documentation, and to bestow a justifiable standard of care. But what defines standard of care and who delineates such standards is something that lacks clarity. The American Society for Gastrointestinal Endoscopy (ASGE) has recently released updated guidelines on the use of sedation and anaesthesia for gastrointestinal endoscopic procedures. Almost simultaneously, the American Society of Anesthesiologists (ASA) has brought out practice guidelines for moderate sedation and analgesia. In contrast to the ASA recommendations, ASGE does not view capnography as an essential monitoring modality for endoscopic procedures with moderate sedation because it has apparently not been shown to improve patient safety. However, they do agree that evidence supports its deployment during deep sedation. These differences in views between guidelines published by societies of substantial academic and clinical standing can confuse the agreement over what constitutes standard of care for the particular speciality. It is the expectation that guidelines and consensus statements in anaesthesiology be preferably issued by national or international organizations of the same speciality.

Parida|Satyen|S|
Kundra|Pankaj|P|
Mohan|V K|VK|
Mishra|Sandeep K|SK|

standard of care
sedation
endoscopy
guidelines
Capnography


Cardio-Metabolic Risk Factors in Scottish South Asian and Caucasian Youth.

Abstract: (1) Background: Scotland has one of the highest rates of obesity in the Western World, it is well established that poor weight profiles, and particularly abdominal obesity, is strongly associated with Type II diabetes and cardiovascular diseases. Whether these associations are apparent in ethnic population groups in Scotland is unclear. The purpose of this study was to examine the associations between different measures of fatness with clustered cardio metabolic risk factors between Scottish South Asian adolescents and Scottish Caucasian adolescents; (2) Methods: A sample of 208 Caucasian adolescents and 52 South Asian adolescents participated in this study. Stature, waist circumference, body mass index, blood pressure, physical activity, and cardiovascular disease (CVD) risk were measured; (3) Results: Significant, partial correlations in the South Asian cohort between body mass index (BMI) and individual risk factors were generally moderate. However, correlations between Waist circumference (WC) and individual risk factors were significant and strong. In the Caucasian cohort, a significant yet weak correlation between WC and total cholesterol (TG) was noted although no other associations were evident for either WC or BMI. Multiple regression analysis revealed that both BMI and WC were positively associated with CCR (p < 0.01) in the South Asian group and with the additional adjustment of either WC or BMI, the independent associations with clustered cardio-metabolic risk (CCR) remained significant (p < 0.005); (4) Conclusions: No positive relationships were found between BMI, WC, and CCR in the Caucasian group. Strong and significant associations between measures of fatness and metabolic risk were evident in Scottish South Asian adolescents.

South Asians
obesity
ethnicity
cardio metabolic risk
adiposity


Clinical biomarker discovery by SWATH-MS based label-free quantitative proteomics: impact of criteria for identification of differentiators and data normalization method.

Abstract:
BACKGROUND
SWATH-MS has emerged as the strategy of choice for biomarker discovery due to the proteome coverage achieved in acquisition and provision to re-interrogate the data. However, in quantitative analysis using SWATH, each sample from the comparison group is run individually in mass spectrometer and the resulting inter-run variation may influence relative quantification and identification of biomarkers. Normalization of data to diminish this variation thereby becomes an essential step in SWATH data processing. In most reported studies, data normalization methods used are those provided in instrument-based data analysis software or those used for microarray data. This study, for the first time provides an experimental evidence for selection of normalization method optimal for biomarker identification.

METHODS
The efficiency of 12 normalization methods to normalize SWATH-MS data was evaluated based on statistical criteria in 'Normalyzer'-a tool which provides comparative evaluation of normalization by different methods. Further, the suitability of normalized data for biomarker discovery was assessed by evaluating the clustering efficiency of differentiators, identified from the normalized data based on p-value, fold change and both, by hierarchical clustering in Genesis software v.1.8.1.

RESULTS
Conventional statistical criteria identified VSN-G as the optimal method for normalization of SWATH data. However, differentiators identified from VSN-G normalized data failed to segregate test and control groups. We thus assessed data normalized by eleven other methods for their ability to yield differentiators which segregate the study groups. Datasets in our study demonstrated that differentiators identified based on p-value from data normalized with Loess-R stratified the study groups optimally.

CONCLUSION
This is the first report of experimentally tested strategy for SWATH-MS data processing with an emphasis on identification of clinically relevant biomarkers. Normalization of SWATH-MS data by Loess-R method and identification of differentiators based on p-value were found to be optimal for biomarker discovery in this study. The study also demonstrates the need to base the choice of normalization method on the application of the data.

Narasimhan|Mythreyi|M| Kannan|Sadhana|S| Chawade|Aakash|A| Bhattacharjee|Atanu|A| Govekar|Rukmini|R|0000-0003-0515-2276

D015415:Biomarkers
D016022:Case-Control Studies
D066264:Datasets as Topic
D003937:Diagnosis, Differential
D004926:Escherichia coli
D005069:Evaluation Studies as Topic
D006367:HeLa Cells
D006801:Humans
D020014:K562 Cells
D013058:Mass Spectrometry
D010446:Peptide Fragments
D020543:Proteome
D040901:Proteomics
D012015:Reference Standards
D012016:Reference Values
D012984:Software
D013194:Staining and Labeling
D015003:Yeasts

Proteomic
Normalization
SWATH
p-value
Fold change
LC–MS


Pre- and post-natal factors and physical activity in childhood: The Norwegian Mother, Father and Child Cohort study.

Abstract: Few studies have examined the possibility that pre- and post-natal factors may be non-linearly associated with later physical activity. We used data from the Norwegian Mother, Father and Child Cohort study (MoBa) and the Medical Birth Registry of Norway (MBRN), including 48 672 children with available data on leisure time physical activity (LTPA) at child's age 7 years. Restricted cubic and linear splines or linear regression was used to examine the associations between maternal pre-pregnancy BMI, birth weight for gestational age, and infant weight gain from birth to 1 year with LTPA (frequency/wk) in 7-year-old children. The results suggest no associations between maternal pre-pregnancy BMI, birth weight, and infant weight gain on subsequent LTPA in girls. Maternal pre-pregnancy BMI and birth weight may be non-linearly associated with LTPA in 7-year-old boys. Infant weight gain (change in weight z-score from birth to 1 year) may be weakly linearly associated with LTPA in boys. Pre- and post-natal factors may therefore influence LTPA in childhood differently in boys and girls. Maternal pre-pregnancy BMI and birth weight are positively associated with LTPA at the lower ends of the maternal pre-pregnancy BMI and birth weight continuums in boys. The negative associations at the higher ends of the continuums and the positive association between infant weight gain and LTPA in boys may not be important and needs further replication.

physical activity
MoBa
maternal pre-pregnancy BMI
infant weight gain
DOHaD
birthweight
determinants


Effects of Pregnane X Receptor Genetic Polymorphisms on Stable Warfarin Doses.

Abstract:
OBJECTIVE
Pregnane X receptor (PXR) is a transcriptional regulator of many drug-metabolizing enzymes including cytochrome P450 (CYP) 2C9. The objective of this study was to assess the possible association between PXR single-nucleotide polymorphisms (SNPs) and stable warfarin doses.

METHODS
A total of 201 patients with stable warfarin doses from the EwhA-Severance Treatment (EAST) Group of Warfarin were included in this study. The influence of genetic polymorphisms on stable warfarin doses was investigated by genotyping 11 SNPs, that is, vitamin K epoxide reductase complex 1 (VKORC1) rs9934438, CYP2C9 rs1057910, CYP4F2 rs2108622, constitutive androstane receptor (CAR) rs2501873, hepatocyte nuclear factor 4α (HNF4α) rs3212198, and PXR (rs3814055, rs1403526, rs3732357, rs3732360, rs2276707 and rs2472682). Subgroup analysis was conducted on CYP2C9 wild-type homozygote allele (AA) carriers.

RESULTS
One PXR SNP of rs2472682 (A>C) exhibited significant association with stable warfarin doses in study population and the subgroup; variant homozygote carriers required significantly lower daily doses of warfarin than those carrying wild allele by about 0.8 mg. Approximate 43.7% of overall interindividual variability in warfarin dose requirement was explained by multivariate regression model. VKORC1, CYP2C9, age, CYP4F2, PXR rs2472682, and CAR/HNF4α rs2501873/rs3212198 accounted for 29.6%, 5.9%, 3.7%, 2.3%, 1.3%, and 0.9% of the variability, respectively. PXR SNP of rs2472682 remained a significant factor in CYP2C9 wild-type homozygote carriers based on univariate and multivariate analyses. The combination of CAR/HNF4α/PXR SNPs of rs2501873/rs3212198/rs2472682 showed about 1 mg dose difference between grouped genotypes in study population and subgroup.

CONCLUSION
Our results revealed that PXR could be a determinant of stable warfarin doses.

Moon|Jung Yeon|JY|
Chang|Byung Chul|BC|
Lee|Kyung Eun|KE|
Bang|Jun Seok|JS|
Gwak|Hye Sun|HS|

D019918:Heart Valve Prosthesis Implantation

warfarin
PXR
single-nucleotide polymorphism
CYP2C9
transcription factor


Mene Mene Tekel Upharsin: Clerical Speed and Elementary Cognitive Speed are Different by Virtue of Test Mode Only.

Abstract: Current taxonomies of intelligence comprise two factors of mental speed, clerical speed (Gs), and elementary cognitive speed (Gt). Both originated from different research traditions and are conceptualized as dissociable constructs in current taxonomies. However, previous research suggests that tasks of one category can be transferred into the other category by simply changing the mode of administration, i.e., in form of a paper-and-pencil test or in from of a computer-based elementary cognitive task. However, cross-mode correlations for specific tasks are usually only moderate. In the present study, mental speed was assessed as a broad construct across different tasks and stimulus materials. This allowed modeling mental speed as a hierarchical construct for paper-and-pencil as well as for computer-based tests. Cross-mode correlations of the respective general factors were moderate (r = 0.64), while the cross-mode correlations of task-specific components depended on task type (r = 0.12 to r = 0.71). Only the g factors of mental speed, but not the task-specific components, were found to be related with working memory capacity as a marker of cognitive ability. The speed general factor modeled across computer-based tests was more highly correlated with working memory capacity (r = 0.66) than the general factor modeled across paper-and-pencil tests (r = 0.46). These findings corroborate a crucial role of the assessment method and imply that validity of speed tests is affected by the choice of the test format.

mental speed
assessment mode
computer-based assessment
paper and pencil


Does a two-element muscle model offer advantages when estimating ankle plantar flexor forces during human cycling?

Abstract: Traditional Hill-type muscle models, parameterized using high-quality experimental data, are often "too weak" to reproduce the joint torques generated by healthy adults during rapid, high force tasks. This study investigated whether the failure of these models to account for different types of motor units contributes to this apparent weakness; if so, muscle-driven simulations may rely on excessively high muscle excitations to generate a given force. We ran a series of forward simulations that reproduced measured ankle mechanics during cycling at five cadences ranging from 60 to 140 RPM. We generated both "nominal" simulations, in which an abstract ankle model was actuated by a 1-element Hill-type plantar flexor with a single contractile element (CE), and "test" simulations, in which the same model was actuated by a 2-element plantar flexor with two CEs that accounted for the force-generating properties of slower and faster motor units. We varied the total excitation applied to the 2-element plantar flexor between 60 and 105% of the excitation from each nominal simulation, and we varied the amount distributed to each CE between 0 and 100% of the total. Within this test space, we identified the excitation level and distribution, at each cadence, that best reproduced the plantar flexor forces generated in the nominal simulations. Our comparisons revealed that the 2-element model required substantially less total excitation than the 1-element model to generate comparable forces, especially at higher cadences. For instance, at 140 RPM, the required excitation was reduced by 23%. These results suggest that a 2-element model, in which contractile properties are "tuned" to represent slower and faster motor units, can increase the apparent strength and perhaps improve the fidelity of simulations of tasks with varying mechanical demands.

Lai|Adrian K M|AKM|
Arnold|Allison S|AS|
Biewener|Andrew A|AA|
Dick|Taylor J M|TJM|
Wakeling|James M|JM|

Modelling
Plantar flexor
Cycling
Hill-type model
Motor recruitment


Role of Hypofractionated Stereotactic Radiosurgery in Recurrent Pineal Parenchymal Tumors of Intermediate Differentiation: A Case Report and Review of the Literature.

Abstract: A pineal parenchymal tumor of intermediate differentiation (PPID) is a rare entity, and optimal treatment is still unclear. Combined multimodality treatment should be considered in PPID due to high recurrence rates. Gross total resection is the first choice of treatment, however, it may not be feasible in every case due to location. Stereotactic radiosurgery (SRS) can be considered for the treatment of primary and recurrent disease, as it enables us to deliver a high radiation dose to the target while minimizing radiation exposure to normal tissue. In this report, we present a case treated with hypofractionated SRS for recurrent/metastatic PPID after the primary tumor was controlled with the combination of surgery and conventionally fractionated radiotherapy.

Beduk Esen|Caglayan Selenge|CS|
Yazici|Gozde|G|
Berker|Mustafa|M|
Zorlu|Faruk|F|


Response of Trichogramma spp. (Hymenoptera: Trichogrammatidae) to Insecticides at Concentrations Sublethal to Cnaphalocrocis medinalis (Lepidoptera: Pyralidae).

Abstract: Trichogramma japonicum Ashmead (Hymenoptera: Trichogrammatidae) and Trichogramma dendrolimi Matsumura (Hymenoptera: Trichogrammatidae) are important parasitoids of Lepidopteran pests and are used for biological control in rice fields. In this study, the response of two of these parasitoids to four insecticides (chlorpyrifos, chlorantraniliprole, emamectin benzoate, and spinosad) were evaluated at target sublethal concentrations (TSC10 and TSC25, representing the LC10 and LC25 to the target pest) of the important rice pest, Cnaphalocrocis medinalis (Guenée). Each of the insecticides led to the mortality of adult T. japonicum and T. dendrolimi at TSC10 and TSC25, whereas no significant differences in the mortality of T. japonicum between TSC10 of chlorantraniliprole and control groups occurred. The parasitic capacity increased at F0 of T. japonicum at the two TSCs of spinosad treated host eggs, whereas the TSC10 was lower for emamectin benzoate at F1 for T. japonicum. The TSCs of chlorpyrifos treated host eggs negatively influenced the emergence rates of T. japonicum at F1. Emamectin benzoate with TSC10 reduced the female ratio of T. japonicum at F1. For T. dendrolimi, the TSCs of chlorpyrifos treated host eggs negatively influenced the emergence rates at F1. These findings indicate that T. japonicum and T. dendrolimi are affected by insecticides at TSCs, and among the four insecticides, chlorantraniliprole had the lowest mortality rates for T. japonicum and T. dendrolimi at TSCs.

Yang|Yajun|Y| Wang|Caiyun|C| Xu|Hongxing|H| Tian|Junce|J| Lu|Zhongxian|Z|

rice
chlorpyrifos
chlorantraniliprole
parasitic wasps
target sublethal concentration (TSC)


Functionalization of silicene and silicane with benzaldehyde.

Abstract: Organic functionalization of nanomaterials offers exceptional flexibility in materials design, and applications in molecular sensors and molecular electronics are expected. However, more studies should be conducted to understand the interaction between nanomaterials and organic molecules. In this work, we studied the functionalization of silicene and silicane with benzaldehyde, performing nudged elastic band calculations within density functional theory. We calculated the structural changes of the adsorption process, electronic properties of the main states, and the energetics. In silicene, the adsorption of benzaldehyde on the top site was found to be the most stable, with an adsorption energy of -0.55 eV. For silicane, the functionalization proceeds through a self-propagating reaction on a highly reactive dangling bond generated by a hydrogen atom vacancy. Benzaldehyde adsorbed on this site depicts an adsorption energy of -1.39 eV, which is larger than in bare silicene. Upon attaching, the double C=O bond breaks down turning the molecule into a highly reactive radical, which in this case, abstracts a neighboring H atom of the sheet. This process is highly achievable since the energy barrier to abstract the H atoms is 0.81 eV, whereas the one needed to desorb the molecule is 1.39 eV. After H abstraction, a new dangling bond is generated at the substrate, making a chain reaction possible to potentially form benzaldehyde monolayers. Organic functionalization is an excellent tool to engineer properties of 2D systems, and having a deeper understanding of the adsorption processes is the first step toward the development of new generation devices. Graphical abstract Benzaldehyde adsorbed on silicene and silicane.

Silicene
Silicane
Benzaldehyde
Adsorption process
Dangling bond
Energy barrier
Radical-initiated reaction


Family History Influences the Effectiveness of Home Exercise in Older People With Chronic Low Back Pain: A Secondary Analysis of a Randomized Controlled Trial.

Abstract:
OBJECTIVE
To investigate whether a family history of low back pain (LBP) influences patient outcomes and treatment effects following home exercises in older people with chronic LBP.

DESIGN
Secondary analysis of a randomized controlled trial.

SETTING
Local community.

PARTICIPANTS
People older than 55 years with chronic LBP (N=60).

INTERVENTIONS
Participants in the intervention group completed video game exercises for 60 minutes 3 times per week for 8 weeks. Participants in the control group were instructed to maintain their usual levels of activity and care seeking behaviors.

MAIN OUTCOMES MEASURES
Participants indicated whether any of their immediate family members had a history of "any" LBP or "activity-limiting" LBP at baseline. We collected self-reported measures of pain, function, pain self-efficacy, care seeking, physical activity, disability, fear of movement and/or reinjury, and falls efficacy at baseline, 8 weeks, 3 months, and 6 months. We performed regression analyses to determine whether a family history of LBP predicted patient outcomes and moderated the effects of home exercise.

RESULTS
Participants with a family history of any LBP were less likely to be highly active than those without a family history (odds ratio, 0.08; 95% CI, 0.01-0.42; P=.003). Home-based video game exercises led to improvements in function in those without a family history of activity-limiting LBP (β=1.78; 95% CI, 0.56-3.00; P=.006) but not in those with a family history (β=-0.17; 95% CI, -2.56 to 2.21; P=.880) (interaction P=.049). A family history of LBP did not influence the remaining patient outcomes or treatment effects.

CONCLUSIONS
A family history of LBP appears to negatively influence physical activity levels in older people with chronic LBP. Further, home-based video game exercises appear to be beneficial for older people with chronic LBP that do not have a family history of LBP.

Zadro|Joshua R|JR|
Shirley|Debra|D|
Nilsen|Tom I L|TIL|
Mork|Paul J|PJ|
Ferreira|Paulo H|PH|

D010342:Patient Acceptance of Health Care

Exercise
Low back pain
Video games
Aged
Medical history taking
Rehabilitation


A Perspective on Reversibility of Tendinosis-Induced Multi-Level Adaptations.

Abstract: Achilles tendinopathy is a well-known pathology that can display interindividual variations in chronicity, symptom presentation, and tendon morphology. Furthermore, symptoms may fluctuate within an individual throughout the stages of the pathology. Although pain is often used as a marker of condition severity, individuals may not consistently report pain due to periods of remission. Persons with tendinosis, which is characterized by advanced morphological alterations, have shown consistent changes in neuromechanics that indicate adaptations in the sensory-motor and the central nervous systems. The current treatment strategy involves repetitive resistance exercise aiming to achieve recovery of lost function. This treatment approach, however, has gauged such functional recovery through symptom relief and return to sport, which, in our opinion, may not suffice and may not prevent symptom recurrence or tendon rupture. In this physiologically informed perspective, we briefly review what is currently known about the consequences of Achilles tendon degeneration and examine the topic of reversing these changes. Shortcomings of contemporary treatment strategies are discussed and we therefore call for a new paradigm to focus on the whole-body level, targeting not only the tendon but also the reversal of the neuromotor control system adaptations.

tendinopathy
neuromechanics
feedforward
motor control
plasticity
spinal reflex
stiffness


Repair of microdamage caused by cyclic loading in insect cuticle.

Abstract: It is well known that repeated loading cycles can reduce the strength of a material and cause eventual failure by the gradual build-up of damage. Previous work has shown that mammalian bone is able to extend its life almost indefinitely by continuously repairing microdamage, preventing the development of macroscopic cracks. However, no study has been conducted until now to investigate repair of microdamage in any other biological material. We applied cyclic bending loads to the hind tibiae of desert locusts (Schistocerca gregaria). We observed a significant decrease in the elastic stiffness (Young's modulus) of the cuticle during the five applied loading cycles, indicating that microdamage had been induced. The tibiae were then left to rest for various time periods: 1 hr, 24 hr, 1 week, and 4 weeks. When tested again after up to 24 hr, there was still a significant decrease in stiffness, showing that some microdamage remained. However, in the samples left for 1 week or 4 weeks before retesting, this decrease in stiffness had disappeared, indicating that the microdamage had been repaired. This is the first ever indication that insects are capable of repairing microdamage. It is a highly significant finding-insects such as locusts rely on the stiffness and strength of their hind legs for jumping. This study suggests that, within a time period of order of a few days, the insect can fully restore the mechanical function of an overloaded leg and thus return to normal activities.

repair insect cuticle strength damage stiffness


Understanding Plant Cellulose Synthases through a Comprehensive Investigation of the Cellulose Synthase Family Sequences.

Abstract: The development of cellulose as an organizing structure in the plant cell wall was a key event in both the initial colonization and the subsequent domination of the terrestrial ecosystem by vascular plants. A wealth of experimental data has demonstrated the complicated genetic interactions required to form the large synthetic complex that synthesizes cellulose. However, these results are lacking an extensive analysis of the evolution, specialization, and regulation of the proteins that compose this complex. Here we perform an in-depth analysis of the sequences in the cellulose synthase (CesA) family. We investigate the phylogeny of the CesA family, with emphasis on evolutionary specialization. We define specialized clades and identify the class-specific regions within the CesA sequence that may explain this specialization. We investigate changes in regulation of CesAs by looking at the conservation of proposed phosphorylation sites. We investigate the conservation of sites where mutations have been documented that impair CesA function, and compare these sites to those observed in the closest cellulose synthase-like (Csl) families to better understand what regions may separate the CesAs from other Csls. Finally we identify two positions with strong conservation of the aromatic trait, but lacking conservation of amino acid identity, which may represent residues important for positioning the sugar substrate for catalysis. These analyses provide useful tools for understanding characterized mutations and post-translational modifications, and for informing further experiments to probe CesA assembly, regulation, and function through site-directed mutagenesis or domain swapping experiments.

cellulose
cellulose synthase
CesA
CslD
CslF
cellulose synthase superfamily
comparative phylogenetics
sequence-based analysis


A Plant Gene Encoding One-Heme and Two-Heme Hemoglobins With Extreme Reactivities Toward Diatomic Gases and Nitrite.

Abstract: In plants, symbiotic hemoglobins act as carriers and buffers of O2 in nodules, whereas nonsymbiotic hemoglobins or phytoglobins (Glbs) are ubiquitous in tissues and may perform multiple, but still poorly defined, functions related to O2 and/or nitric oxide (NO). Here, we have identified a Glb gene of the model legume Medicago truncatula with unique properties. The gene, designated MtGlb1-2, generates four alternative splice forms encoding Glbs with one or two heme domains and 215-351 amino acid residues. This is more than double the size of any hemoglobin from plants or other organisms described so far. A combination of molecular, cellular, biochemical, and biophysical methods was used to characterize these novel proteins. RNA-sequencing showed that the four splice variants are expressed in plant tissues. MtGlb1-2 is transcriptionally activated by hypoxia and its expression is further enhanced by an NO source. The gene is preferentially expressed in the meristems and vascular bundles of roots and nodules. Two of the proteins, bearing one or two hemes, were characterized using mutants in the distal histidines of the hemes. The Glbs are extremely reactive toward the physiological ligands O2, NO, and nitrite. They show very high O2 affinities, NO dioxygenase activity (in the presence of O2), and nitrite reductase (NiR) activity (in the absence of O2) compared with the hemoglobins from vertebrates and other plants. We propose that these Glbs act as either NO scavengers or NO producers depending on the O2 tension in the plant tissue, being involved in the fast and fine tuning of NO concentration in the cytosol in response to sudden changes in O2 availability.

Villar|Irene|I|
Larrainzar|Estíbaliz|E|
Milazzo|Lisa|L|
Pérez-Rontomé|Carmen|C|
Rubio|Maria C|MC|
Smulevich|Giulietta|G|
Martínez|Jesús I|JI|
Wilson|Michael T|MT|
Reeder|Brandon|B|
Huertas|Raul|R|
Abbruzzetti|Stefania|S|
Udvardi|Michael|M|
Becana|Manuel|M|

nodule
phytoglobins
nitric oxide
Medicago truncatula
hypoxia
leghemoglobin
nitrate
symbiosis


APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway.

Abstract: Adenomatous polyposis coli (APC) mutations cause Wnt pathway activation in human cancers. Current models for APC action emphasize its role in promoting β-catenin degradation downstream of Wnt receptors. Unexpectedly, we find that blocking Wnt receptor activity in APC-deficient cells inhibits Wnt signaling independently of Wnt ligand. We also show that inducible loss of APC is rapidly followed by Wnt receptor activation and increased β-catenin levels. In contrast, APC2 loss does not promote receptor activation. We show that APC exists in a complex with clathrin and that Wnt pathway activation in APC-deficient cells requires clathrin-mediated endocytosis. Finally, we demonstrate conservation of this mechanism in Drosophila intestinal stem cells. We propose a model in which APC and APC2 function to promote β-catenin degradation, and APC also acts as a molecular "gatekeeper" to block receptor activation via the clathrin pathway.

Saito-Diaz|Kenyi|K|
Benchabane|Hassina|H|
Tiwari|Ajit|A|
Tian|Ai|A|
Li|Bin|B|
Thompson|Joshua J|JJ|
Hyde|Annastasia S|AS|
Sawyer|Leah M|LM|
Jodoin|Jeanne N|JN|
Santos|Eduardo|E|
Lee|Laura A|LA|
Coffey|Robert J|RJ|
Beauchamp|R Daniel|RD|
Williams|Christopher S|CS|
Kenworthy|Anne K|AK|
Robbins|David J|DJ|
Ahmed|Yashi|Y|
Lee|Ethan|E|

D025601:Adenomatous Polyposis Coli Protein

APC
Wnt signaling
clathrin
β-catenin
endocytosis
LRP6
caveolin
colorectal cancer


Calcium signalling in medial intercalated cell dendrites and spines.

Abstract:
KEY POINTS
Dendritic and spine calcium imaging in combination with electrophysiology in acute slices revealed that in medial intercalated cells of the amygdala: Action potentials back-propagate into the dendritic tree, but due to the presence of voltage-dependent potassium channels, probably Kv4.2 channels, attenuate over distance. A mixed population of AMPA receptors with rectifying and linear I-V relations are present at individual spines of a single neuron. Decay kinetics and pharmacology suggest tri-heteromeric NMDA receptors at basolateral-intercalated cell synapses. NMDA receptors are the main contributors to spine calcium entry in response to synaptic stimulation. Calcium signals in response to low- and high-frequency stimulation, and in combination with spontaneous action potentials are locally restricted to the vicinity of active spines. Together, these data show that calcium signalling in these GABAergic neurons is tightly controlled and acts as a local signal.

ABSTRACT
The amygdala plays a central role in fear conditioning and extinction. The medial intercalated (mITC) neurons are GABAergic cell clusters interspaced between the basolateral (BLA) and central amygdala (CeA). These neurons are thought to play a key role in fear and extinction, controlling the output of the CeA by feed-forward inhibition. BLA to mITC cell inputs are thought to undergo synaptic plasticity, a mechanism underlying learning, which is mediated by NMDA receptor-dependent mechanisms that require changes in cytosolic calcium. Here, we studied the electrical and calcium signalling properties of mITC neurons in GAD67-eGFP mice using whole-cell patch clamp recordings and two-photon calcium imaging. We show that action potentials back-propagate (bAP) into dendrites, and evoke calcium transients in both the shaft and the dendritic spine. However, bAP-mediated calcium rises in the dendrites attenuate with distance due to shunting by voltage-gated potassium channels. Glutamatergic inputs make dual component synapses on spines. At these synapses, postsynaptic AMPA receptors can have linear or rectifying I-V relationships, indicating that some synapses express GluA2-lacking AMPA receptors. Synaptic NMDA receptors had intermediate decay kinetics, and were only partly blocked by GuN2B selective blockers, indicating these receptors are GluN1/GluN2A/GluN2B trimers. Low- or high-frequency synaptic stimulation raised spine calcium, mediated by calcium influx via NMDA receptors, was locally restricted and did not invade neighbouring spines. Our results show that in mITC neurons, postsynaptic calcium is tightly controlled, and acts as a local signal.

intercalated amygdala fear extinction learning


Diffuse alveolar haemorrhage and Libman-Sacks endocarditis: a rare presentation of antiphospholipid syndrome.

Abstract: A 26-year-old woman with a history of idiopathic thrombocytopaenic purpura and a 1-year history of blood-streaked sputum presented after a severe episode of haemoptysis with dyspnoea. Chest imaging revealed diffuse ground glass and bronchovascular nodules. Bronchoscopy revealed bilateral diffuse alveolar haemorrhage (DAH). Sputum and bronchoalveolar lavage studies were negative for infectious aetiologies. A transthoracic echocardiogram revealed Libman-Sacks endocarditis with severe mitral regurgitation and physical examination revealed retinal artery occlusion and Osler's nodes. The patient had an increased anticardiolipin Immunoglobulin IgG and anti-B2 glycoprotein IgG, suggesting antiphospholipid syndrome (APLS). The patient was then started on high-dose methylprednisolone and had an improvement in her dyspnoea and haemoptysis. She was also started on anticoagulation as treatment for Libman-Sacks endocarditis. APLS should be considered as a possible underlying aetiology for unusual presentations of DAH with concurrent Libman-Sacks endocarditis in non-intravenous drug users with existing autoimmune disorders.

haematology (incl blood transfusion)
malignant and benign haematology
respiratory medicine
rheumatology
valvar diseases


Improving tuberculosis surveillance by detecting international transmission using publicly available whole genome sequencing data.

Abstract: IntroductionImproving the surveillance of tuberculosis (TB) is especially important for multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. The large amount of publicly available whole genome sequencing (WGS) data for TB gives us the chance to re-use data and to perform additional analyses at a large scale.AimWe assessed the usefulness of raw WGS data of global MDR/XDR Mycobacterium tuberculosis isolates available from public repositories to improve TB surveillance.MethodsWe extracted raw WGS data and the related metadata of M. tuberculosis isolates available from the Sequence Read Archive. We compared this public dataset with WGS data and metadata of 131 MDR- and XDR M. tuberculosis isolates from Germany in 2012 and 2013.ResultsWe aggregated a dataset that included 1,081 MDR and 250 XDR isolates among which we identified 133 molecular clusters. In 16 clusters, the isolates were from at least two different countries. For example, Cluster 2 included 56 MDR/XDR isolates from Moldova, Georgia and Germany. When comparing the WGS data from Germany with the public dataset, we found that 11 clusters contained at least one isolate from Germany and at least one isolate from another country. We could, therefore, connect TB cases despite missing epidemiological information.ConclusionWe demonstrated the added value of using WGS raw data from public repositories to contribute to TB surveillance. Comparing the German with the public dataset, we identified potential international transmission events. Thus, using this approach might support the interpretation of national surveillance results in an international context.

Sanchini|Andrea|A|
Jandrasits|Christine|C|
Tembrockhaus|Julius|J|
Kohl|Thomas Andreas|TA|
Utpatel|Christian|C|
Maurer|Florian P|FP|
Niemann|Stefan|S|
Haas|Walter|W|
Renard|Bernhard Y|BY|
Kröger|Stefan|S|

D024901:Drug Resistance, Multiple, Bacterial

genomic sequencing data
mycobacterium tuberculosis
public repositories
molecular cluster
molecular surveillance
multidrug-resistant tuberculosis


Effect of thrombus aspiration on postprocedural outcomes in elderly patients with acute ST-elevation myocardial ınfarction.

Abstract:
AIM
The effects of thrombus aspiration (TA) during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) have been evaluated in several studies. The aim of the present study was to evaluate postprocedural outcomes in elderly STEMI patients who have a tendency for vasoconstruction and decreased coronary flow reserve.

METHODS
A total of 124 patients (aged ≥65 years) with STEMI who underwent primary PCI (71.2% men, 29.8% women, mean age 74 ± 7 years) were enrolled in the study. Patients were divided into two groups according to intervention with and without TA. Acute angiographic, electrocardiographic and echocardiographic results were compared between the two groups.

RESULTS
TA was carried out in 42 patients (33.8%). Baseline clinical characteristics and predischarge echocardiographic features did not differ between TA(+) and TA(-) patients (ejection fraction 37.26 ± 8.91 vs 38.53 ± 11.18, P = 0.558, wall motion index 1.69 ± 0.38 vs 1.76 ± 0.37, P = 0.316, septal E' 0.058 ± 0.022 vs 0.053 ± 0.015, P = 0.267, E/E' 11.82 ± 4.30 vs 13.12 ± 5.09, P = 0.370). Acute angiographic and electrocardiographic results did not differ between the two groups, but were slightly better in the thrombectomy group than those without TA corrected TIMI frame count (31.63 ± 16.33 vs 34.97 ± 15.81, P = 0.197, TIMI-3 88.1% vs 79.3%, P = 0.223, ST segment resolution 81.3% vs 70.3%, P = 0.250).

CONCLUSIONS
Thrombectomy during primary PCI has no effect on postprocedural outcomes in an elderly group with STEMI. Geriatr Gerontol Int 2015; ●●: ●●-●●.

Emre|Ender|E| Ural|Ertan|E| Kahraman|Göksel|G| Bildirici|Ulas|U| Kilic|Teoman|T| Bozyel|Serdar|S| Onuk|Raşik|R| Akbulut|Tayyar|T| Ural|Dilek|D|

D000072657:ST Elevation Myocardial Infarction


Informing Antibiotic Treatment Decisions: Evaluating Rapid Molecular Diagnostics To Identify Susceptibility and Resistance to Carbapenems against Acinetobacter spp. in PRIMERS III.

Abstract: The widespread dissemination of carbapenem-resistant Acinetobacter spp. has created significant therapeutic challenges. At present, rapid molecular diagnostics (RMDs) that can identify this phenotype are not commercially available. Two RMD platforms, PCR combined with electrospray ionization mass spectrometry (PCR/ESI-MS) and molecular beacons (MB), for detecting genes conferring resistance/susceptibility to carbapenems in Acinetobacter spp. were evaluated. An archived collection of 200 clinical Acinetobacter sp. isolates was tested. Predictive values for susceptibility and resistance were estimated as a function of susceptibility prevalence and were based on the absence or presence of beta-lactamase (bla) NDM, VIM, IMP, KPC, and OXA carbapenemase genes (e.g., blaOXA-23, blaOXA-24/40, and blaOXA-58 found in this study) against the reference standard of MIC determinations. According to the interpretation of MICs, 49% (n = 98) of the isolates were carbapenem resistant (as defined by either resistance or intermediate resistance to imipenem). The susceptibility sensitivities (95% confidence interval [CI]) for imipenem were 82% (74%, 89%) and 92% (85%, 97%) for PCR/ESI-MS and MB, respectively. Resistance sensitivities (95% CI) for imipenem were 95% (88%, 98%) and 88% (80%, 94%) for PCR/ESI-MS and MB, respectively. PRIMERS III establishes that RMDs can discriminate between carbapenem resistance and susceptibility in Acinetobacter spp. In the context of a known prevalence of resistance, SPVs and RPVs can inform clinicians regarding the best choice for empiric antimicrobial therapy against this multidrug-resistant pathogen.

D000150:Acinetobacter
D000900:Anti-Bacterial Agents
D001426:Bacterial Proteins
D015780:Carbapenems
D017931:DNA Primers
D006801:Humans
D008826:Microbial Sensitivity Tests
D057089:Pathology, Molecular
D011237:Predictive Value of Tests
D012680:Sensitivity and Specificity
D013997:Time Factors
D018440:beta-Lactam Resistance
D001618:beta-Lactamases


NICU Human Milk Dose and 20-Month Neurodevelopmental Outcome in Very Low Birth Weight Infants.

Abstract:
BACKGROUND
The association between human milk (HM) feeding in the NICU and neurodevelopmental (ND) outcome in very low birth weight (VLBW) infants is unclear. Limitations of previous studies include a lack of exact estimates of HM dose and of generalizability to minority populations.

OBJECTIVE
To determine the impact on ND outcome of an exact dose of HM received in the NICU in a diverse, contemporary cohort of VLBW infants.

METHODS
We included 430 VLBW infants born in the period 2008-2012 for whom the mean daily dose (DD) of HM received during the stay in the NICU (NICU HM-DD) was calculated prospectively from the daily nutritional intake from admission to discharge. Outcomes included Bayley-III index scores at 20 months' corrected age (CA) as assessed upon ND follow-up, which were collected retrospectively. Multivariable linear regression analyses controlled for neonatal and social risk factors.

RESULTS
Each 10 mL/kg/day increase in NICU HM-DD was associated with a 0.35 increase in cognitive index score (95% CI [0.03-0.66], p = 0.03), but no significant associations were detected for the language or motor indices.

CONCLUSIONS
There is a significant dose-dependent association between NICU HM intake and cognitive scores at 20 months' CA. Further follow-up will determine whether these findings persist at school age, and could help alleviate the special-education and health-care burden in this population.

Patra|Kousiki|K|
Hamilton|Matthew|M|
Johnson|Tricia J|TJ|
Greene|Michelle|M|
Dabrowski|Elizabeth|E|
Meier|Paula P|PP|
Patel|Aloka L|AL|

D007227:Infant Nutritional Physiological Phenomena

Human milk
Neurodevelopmental outcome
Very low birth weight infants