bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials
Authors: Asbaghi Omid , Sadeghian Mehdi , Nazarian Behzad , Sarreshtedari Mehrnoosh , Mozaffari-Khosravi Hassan , Maleki Vahid , Alizadeh Mohammad , Shokri Azad , Sadeghi Omid
Published: October 2020

The previous meta-analysis of clinical trials revealed a beneficial effect of vitamin E supplementation on serum C-reactive protein (CRP) concentrations; however, it is unknown whether this vitamin has the same influence on other inflammatory biomarkers. Also, several clinical trials have been published since the release of earlier meta-analysis. Therefore, we aimed to conduct a comprehensive meta-analysis to summarize current evidence on the effects of vitamin E supplementation on inflammatory biomarkers in adults. We searched the online databases using relevant keywords up to November 2019. Randomized clinical trials (RCTs) investigating the effect of vitamin E, compared with the placebo, on serum concentrations of inflammatory cytokines were included. Overall, we included 33 trials with a total sample size of 2102 individuals, aged from 20 to 70 years. Based on 36 effect sizes from 26 RCTs on serum concentrations of CRP, we found a significant reduction following supplementation with vitamin E (− 0.52, 95% CI − 0.80, − 0.23 mg/L, P < 0.001). Although the overall effect of vitamin E supplementation on serum concentrations of interleukin-6 (IL-6) was not significant, a significant reduction in this cytokine was seen in studies that used α-tocopherol and those trials that included patients with disorders related to insulin resistance. Moreover, we found a significant reducing effect of vitamin E supplementation on tumor necrosis factor-α (TNF-α) concentrations at high dosages of vitamin E; such that based on dose–response analysis, serum TNF-α concentrations were reduced significantly at the dosages of ≥ 700 mg/day vitamin E (Pnon-linearity = 0.001). Considering different chemical forms of vitamin E, α-tocopherol, unlike other forms, had a reducing effect on serum levels of CRP and IL-6. In conclusion, our findings revealed a beneficial effect of vitamin E supplementation, particularly in the form of α-tocopherol, on subclinical inflammation in adults. Future high-quality RCTs should be conducted to translate this anti-inflammatory effect of vitamin E to the clinical setting.
Publisher Correction: Rapid Thermal Processing to Enhance Steel Toughness
Authors: Judge V. K. , Speer J. G. , Clarke K. D. , Findley K. O. , Clarke A. J.
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Differentiating Staphylococcus infection-associated glomerulonephritis and primary IgA nephropathy: a mass spectrometry-based exploratory study
Authors: Satoskar Anjali A. , Shapiro John P. , Jones Mikayla , Bott Cherri , Parikh Samir V. , Brodsky Sergey V. , Yu Lianbo , Nagaraja Haikady N. , Wilkey Daniel W. , Merchant Michael L. , Klein Jon B. , Nadasdy Tibor , Rovin Brad H.
Published: October 2020

Staphylococcus infection-associated glomerulonephritis (SAGN) and primary IgA nephropathy (IgAN) are separate disease entities requiring different treatment approaches. However, overlapping histologic features may cause a diagnostic dilemma. An exploratory proteomic study to identify potential distinguishing biomarkers was performed on formalin fixed paraffin embedded kidney biopsy tissue, using mass spectrometry (HPLC–MS/MS) (n = 27) and immunohistochemistry (IHC) (n = 64), on four main diagnostic groups—SAGN, primary IgAN, acute tubular necrosis (ATN) and normal kidney (baseline transplant biopsies). Spectral counts modeled as a negative binomial distribution were used for statistical comparisons and in silico pathway analysis. Analysis of variance techniques were used to compare groups and the ROC curve to evaluate classification algorithms. The glomerular proteomes of SAGN and IgAN showed remarkable similarities, except for significantly higher levels of monocyte/macrophage proteins in SAGN—mainly lysozyme and S100A9. This finding was confirmed by IHC. In contrast, the tubulointerstitial proteomes were markedly different in IgAN and SAGN, with a lower abundance of metabolic pathway proteins and a higher abundance of extracellular matrix proteins in SAGN. The stress protein transglutaminase-2 (TGM2) was also significantly higher in SAGN. IHC of differentially-expressed glomerular and tubulointerstitial proteins can be used to help discriminate between SAGN and IgAN in ambiguous cases.
Differential expression of predisposing HLA-DQ2.5 alleles in DR5/DR7 celiac disease patients affects the pathological immune response to gluten
Authors: Pisapia Laura , Picascia Stefania , Farina Federica , Barba Pasquale , Gianfrani Carmen , Del Pozzo Giovanna
Published: October 2020

The DR5-DQ7/DR7-DQ2 genotype is very frequent among patients affected by celiac disease (CD), in Europe. This genotype, associated to high risk of CD, carries the HLA-DQA1*05and HLA-DQB1*02predisposing alleles, intransconfiguration. The alleles encode the DQ2.5 heterodimer responsible of gluten peptide presentation on the surface of antigen-presenting cells (APCs), and consequent pathogenic CD4+T cell activation. We demonstrated that DR5/DR7 APCs induce an anti-gluten CD4+T cell response, of comparable intensity to that observed with APCs carrying DR1/DR3 genotype, which risk alleles are incisconfiguration. In addition, we showed that DR5/DR7 APCs from celiac patients stimulated an effector CD4+T cell response higher with respect to that induced by DR5/DR7 APCs from healthy subjects. To explain these findings, we assessed the DQ2.5 RNA and protein quantity. We showed that the expression ofDQA1*05andDQB1*02risk alleles is much higher than the expression of non-CD-associated alleles, in agreement with the previous results obtained with DR1/DR3 genotype. The differential expression of transcripts influences the quantity of DQα1*05 and DQβ1*02 chains and, as consequence, the cell surface density of DQ2.5 heterodimers. Moreover, both RNA and proteins, are more abundant in APCs from celiac patients than controls. Finally, to unravel the mechanism regulating the expression of predisposingDQA1*05andDQB1*02alleles, we quantified the new synthetized RNA and found that the differential expression is explained by their transcription rate. Our results confirmed that the strength of antigen-specific CD4+T cell response is mainly determined by the amount of gluten in the diet and provided a new possible approach for a personalized diagnosis and for risk stratification.
Lacrimal gland excision in male and female mice causes ocular pain and anxiety-like behaviors
Authors: Mecum Neal E. , Demers Danielle , Sullivan Cara E. , Denis Tori E. , Kalliel John R. , Meng Ian D.
Published: October 2020

Lacrimal gland excision (LGE) induced dry eye produces more severe corneal damage in female mice, yet signs of LGE-induced ocular pain and anxiety in male and female mice have not been characterized. Excision of either the extraorbital gland (single LGE), or both the extraorbital and intraorbital glands (double LGE) was performed in male and female C57BL/6J mice to induce moderate and severe dry eye. Ongoing pain was assessed by quantifying palpebral opening and evoked nociceptive responses after corneal application of capsaicin and menthol. The open-field and plus maze were used to assess anxiety. Single LGE caused a reduction in palpebral opening and an increase in capsaicin and menthol-evoked responses only in female mice. Furthermore, single LGE produced signs of increased anxiety in female but not male mice. Overall, female mice appear more susceptible to signs of ocular pain, irritation, and anxiety in response to aqueous tear deficiency.
Physical properties of epilithic river biofilm as a new lead to perform pollution bioassessments in overseas territories
Authors: Monti Dominique , Hubas Cedric , Lourenço Xavier , Begarin Farid , Haouisée Alexandre , Romana Laurence , Lefrançois Estelle , Jestin Alexandra , Budzinski Hélène , Tapie Nathalie , Risser Théo , Mansot Jean-Louis , Keith Philippe , Gros Olivier , Lopez Pascal-Jean , Lauga Béatrice
Published: October 2020

Chlordecone (CLD) levels measured in the rivers of the French West Indies were among the highest values detected worldwide in freshwater ecosystems, and its contamination is recognised as a severe health, environmental, agricultural, economic, and social issue. In these tropical volcanic islands, rivers show strong originalities as simplified food webs, or numerous amphidromous migrating species, making the bioindication of contaminations a difficult issue. The objective of this study was to search for biological responses to CLD pollution in a spatially fixed and long-lasting component of the rivers in the West Indies: the epilithic biofilm. Physical properties were investigated through complementary analyses: friction, viscosity as well as surface adhesion were analyzed and coupled with measures of biofilm carbon content and exopolymeric substance (EPS) production. Our results have pointed out a mesoscale chemical and physical reactivity of the biofilm that can be correlated with CLD contamination. We were able to demonstrate that epilithic biofilm physical properties can effectively be used to infer freshwater environmental quality of French Antilles rivers. The friction coefficient is reactive to contamination and well correlated to carbon content and EPS production. Monitoring biofilm physical properties could offer many advantages to potential users in terms of effectiveness and ease of use, rather than more complex or time-consuming analyses.
A single dose of estrogen during hemorrhagic shock protects against Kidney Injury whereas estrogen restoration in ovariectomized mice is ineffective
Authors: Buléon Marie , Cuny Mélodie , Grellier Jimmy , Charles Pierre-Yves , Belliere Julie , Casemayou Audrey , Arnal Jean-François , Schanstra Joost-Peter , Tack Ivan
Published: October 2020

The protective effect of estrogens against chronic glomerular diseases is admitted but remains debated during acute kidney injury (AKI). Using a model of resuscitated hemorrhagic shock in C57/Bl6 female mice, this study evaluated at 1 and 21 days the renal effect of (1) endogenous estrogen, using ovariectomized mice with or without chronic estrogen restoration, or (2) exogenous estrogen, using a single administration of a pharmacological dose during shock resuscitation. In both ovariectomized and intact mice, hemorrhagic shock induced epithelial cell damages (assessed by KIM-1 renal expression) with secondary renal fibrosis but without significant decrease in GFR at day 21. Ovariectomy with or without estrogen restoration have no significant effect on renal damages and dysfunction. This lack of effect was associated with a marked (> 80%) reduction of total kidney GPR30 expression. By contrast, a single high dose of estradiol in intact mice reduced renal KIM-1 expression by 2/3, attenuated the severity of cell death related to pyroptosis, and prevented the increase of fibrosis by 1/3. This provides a rationale to investigate the benefits of a single administration of estrogen or estrogen modulators during acute kidney injuries in males. Furthermore, the cost/benefit ratio of such administration should be investigated in Human.
Nucleosomal embedding reshapes the dynamics of abasic sites
Authors: Bignon Emmanuelle , Claerbout Victor E. P. , Jiang Tao , Morell Christophe , Gillet Natacha , Dumont Elise
Published: October 2020

Apurinic/apyrimidinic (AP) sites are the most common DNA lesions, which benefit from a most efficient repair by the base excision pathway. The impact of losing a nucleobase on the conformation and dynamics of B-DNA is well characterized. Yet AP sites seem to present an entirely different chemistry in nucleosomal DNA, with lifetimes reduced up to 100-fold, and the much increased formation of covalent DNA-protein cross-links leading to strand breaks, refractory to repair. We report microsecond range, all-atom molecular dynamics simulations that capture the conformational dynamics of AP sites and their tetrahydrofuran analogs at two symmetrical positions within a nucleosome core particle, starting from a recent crystal structure. Different behaviours between the deoxyribo-based and tetrahydrofuran-type abasic sites are evidenced. The two solvent-exposed lesion sites present contrasted extrahelicities, revealing the crucial role of the position of a defect around the histone core. Our all-atom simulations also identify and quantify the frequency of several spontaneous, non-covalent interactions between AP and positively-charged residues from the histones H2A and H2B tails that prefigure DNA-protein cross-links. Such an in silico mapping of DNA-protein cross-links gives important insights for further experimental studies involving mutagenesis and truncation of histone tails to unravel mechanisms of DPCs formation.
Wild-type huntingtin regulates human macrophage function
Authors: O’Regan Grace C. , Farag Sahar H. , Ostroff Gary R. , Tabrizi Sarah J. , Andre Ralph
Published: October 2020

The huntingtin (HTT) protein in its mutant form is the cause of the inherited neurodegenerative disorder, Huntington’s disease. Beyond its effects in the central nervous system, disease-associated mutant HTT causes aberrant phenotypes in myeloid-lineage innate immune system cells, namely monocytes and macrophages. Whether the wild-type form of the protein, however, has a role in normal human macrophage function has not been determined. Here, the effects of lowering the expression of wild-type (wt)HTT on the function of primary monocyte-derived macrophages from healthy, non-disease human subjects were examined. This demonstrated a previously undescribed role for wtHTT in maintaining normal macrophage health and function. Lowered wtHTT expression was associated, for instance, with a diminished release of induced cytokines, elevated phagocytosis and increased vulnerability to cellular stress. These may well occur by mechanisms different to that associated with the mutant form of the protein, given an absence of any effect on the intracellular signalling pathway predominantly associated with macrophage dysfunction in Huntington’s disease.
First on-line detection of radioactive fission isotopes produced by laser-accelerated protons
Authors: Boller Pascal , Zylstra Alex , Neumayer Paul , Bernstein Lee , Brabetz Christian , Despotopulos John , Glorius Jan , Hellmund Johannes , Henry Eugene A. , Hornung Johannes , Jeet Justin , Khuyagbaatar Jadambaa , Lens Lotte , Roeder Simon , Stoehlker Thomas , Yakushev Alexander , Litvinov Yuri A. , Shaughnessy Dawn , Bagnoud Vincent , Kuehl Thomas , Schneider Dieter H. G.
Published: October 2020

The on-going developments in laser acceleration of protons and light ions, as well as the production of strong bursts of neutrons and multi-$$\hbox {MeV}$$
MeV
photons by secondary processes now provide a basis for novel high-flux nuclear physics experiments. While the maximum energy of protons resulting from Target Normal Sheath Acceleration is presently still limited to around $$100 \, \hbox {MeV}$$

100

MeV

, the generated proton peak flux within the short laser-accelerated bunches can already today exceed the values achievable at the most advanced conventional accelerators by orders of magnitude. This paper consists of two parts covering the scientific motivation and relevance of such experiments and a first proof-of-principle demonstration. In the presented experiment pulses of $$200 \, \hbox {J}$$

200

J

at $$\approx \, 500 \, \hbox {fs}$$

≈

500

fs

duration from the PHELIX laser produced more than $$10^{12}$$

10
12

protons with energies above $$15 \, \hbox {MeV}$$

15

MeV

in a bunch of sub-nanosecond duration. They were used to induce fission in foil targets made of natural uranium. To make use of the nonpareil flux, these targets have to be very close to the laser acceleration source, since the particle density within the bunch is strongly affected by Coulomb explosion and the velocity differences between ions of different energy. The main challenge for nuclear detection with high-purity germanium detectors is given by the strong electromagnetic pulse caused by the laser-matter interaction close to the laser acceleration source. This was mitigated by utilizing fast transport of the fission products by a gas flow to a carbon filter, where the $$\upgamma$$
γ
-rays were registered. The identified nuclides include those that have half-lives down to $$39 \, \hbox {s}$$

39

s

. These results demonstrate the capability to produce, extract, and detect short-lived reaction products under the demanding experimental condition imposed by the high-power laser interaction. The approach promotes research towards relevant nuclear astrophysical studies at conditions currently only accessible at nuclear high energy density laser facilities.
Statistical models for identifying frequent hitters in high throughput screening
Authors: Goodwin Samuel , Shahtahmassebi Golnaz , Hanley Quentin S.
Published: October 2020

High throughput screening (HTS) interrogates compound libraries to find those that are “active” in an assay. To better understand compound behavior in HTS, we assessed an existing binomial survivor function (BSF) model of “frequent hitters” using 872 publicly available HTS data sets. We found large numbers of “infrequent hitters” using this model leading us to reject the BSF for identifying “frequent hitters.” As alternatives, we investigated generalized logistic, gamma, and negative binomial distributions as models for compound behavior. The gamma model reduced the proportion of both frequent and infrequent hitters relative to the BSF. Within this data set, conclusions about individual compound behavior were limited by the number of times individual compounds were tested (1–1613 times) and disproportionate testing of some compounds. Specifically, most tests (78%) were on a 309,847-compound subset (17.6% of compounds) each tested ≥ 300 times. We concluded that the disproportionate retesting of some compounds represents compound repurposing at scale rather than drug discovery. The approach to drug discovery represented by these 872 data sets characterizes the assays well by challenging them with many compounds while each compound is characterized poorly with a single assay. Aggregating the testing information from each compound across the multiple screens yielded a continuum with no clear boundary between normal and frequent hitting compounds.
Petal abscission in fragrant roses is associated with large scale differential regulation of the abscission zone transcriptome
Authors: Singh Priya , Bharti Neeraj , Singh Amar Pal , Tripathi Siddharth Kaushal , Pandey Saurabh Prakash , Chauhan Abhishek Singh , Kulkarni Abhijeet , Sane Aniruddha P.
Published: October 2020

Flowers of fragrant roses such as Rosa bourboniana are ethylene-sensitive and undergo rapid petal abscission while hybrid roses show reduced ethylene sensitivity and delayed abscission. To understand the molecular mechanism underlying these differences, a comparative transcriptome of petal abscission zones (AZ) of 0 h and 8 h ethylene-treated flowers from R. bourboniana was performed. Differential regulation of 3700 genes (1518 up, 2182 down) representing 8.5% of the AZ transcriptome was observed between 0 and 8 h ethylene-treated R. bourboniana petal AZ. Abscission was associated with large scale up-regulation of the ethylene pathway but prominent suppression of the JA, auxin and light-regulated pathways. Regulatory genes encoding kinases/phosphatases/F-box proteins and transcription factors formed the major group undergoing differential regulation besides genes for transporters, wall modification, defense and phenylpropanoid pathways. Further comparisons with ethylene-treated petals of R. bourboniana and 8 h ethylene-treated AZ (R. hybrida) identified a core set of 255 genes uniquely regulated by ethylene in R. bourboniana AZ. Almost 23% of these encoded regulatory proteins largely conserved with Arabidopsis AZ components. Most of these were up-regulated while an entire set of photosystem genes was prominently down-regulated. The studies provide important information on regulation of petal abscission in roses.
A genotyping method combining primer competition PCR with HRM analysis to identify point mutations in Duchenne animal models
Authors: Lasa-Fernandez Haizpea , Mosqueira-Martín Laura , Alzualde Ainhoa , Lasa-Elgarresta Jaione , Vallejo-Illarramendi Ainara
Published: October 2020

Dystrophin-null sapje zebrafish is an excellent model for better understanding the pathological mechanisms underlying Duchenne muscular dystrophy, and it has recently arisen as a powerful tool for high-throughput screening of therapeutic candidates for this disease. While dystrophic phenotype in sapje larvae can be easily detected by birefringence, zebrafish genotyping is necessary for drug screening experiments, where the potential rescue of larvae phenotype is the primary outcome. Genotyping is also desirable during colony husbandry since heterozygous progenitors need to be selected. Currently, sapje zebrafish are genotyped through techniques involving sequencing or multi-step PCR, which are often costly, tedious, or require special equipment. Here we report a simple, precise, cost-effective, and versatile PCR genotyping method based on primer competition. Genotypes can be resolved by standard agarose gel electrophoresis and high-resolution melt assay, the latter being especially useful for genotyping a large number of samples. Our approach has shown high sensitivity, specificity, and reproducibility in detecting the A/T point mutation in sapje zebrafish and the C/T mutation in the mdx mouse model of Duchenne. Hence, this method can be applied to other single nucleotide substitutions and may be further optimized to detect small insertions and deletions. Given its robust performance with crude DNA extracts, our strategy may be particularly well-suited for detecting single nucleotide variants in poor-quality samples such as ancient DNA or DNA from formalin-fixed, paraffin-embedded material.
Factors predicting final visual outcome in quiescent proliferative diabetic retinopathy
Authors: Kim Jinsoo , Park In Won , Kwon Soonil
Published: October 2020

To investigate factors reflecting visual outcome and macular perfusion in quiescent proliferative diabetic retinopathy (PDR) patients after panretinal photocoagulation (PRP). We included 118 patients with quiescent PDR who had completed PRP. All participants had standardized interview to determine ocular history, smoking status, cardiovascular risk factors, and history of diabetic mellitus (DM). Foveal avascular zone (FAZ) area, retinal vessel density (VD) and vessel length density (VLD) were measured using optical coherence tomography angiography. VD was negatively correlated with hypertension, diabetic foot, HbA1c, and time after PRP (β =  − 0.181, P = 0.046; β =  − 0.231, P = 0.020; β =  − 0.244, P = 0.010; β =  − 0.278, P = 0.029). FAZ area of superficial capillary plexus and deep capillary plexus (DCP) was positively correlated with DM duration and diabetic foot (β = 0.178, P = 0.047; β = 0.293, P = 0.002; β = 0.252, P = 0.045; β = 0.304, P = 0.002). Macular perfusion state in patients with quiescent PDR was associated with diabetic foot, DM duration, HbA1c, and time after PRP. Of note, diabetic foot showed the strongest correlation with macular perfusion among various systemic factors. VLD, especially in DCP was associated with poor visual outcome.
Mitochondrial DNA damage as a potential biomarker of LRRK2 kinase activity in LRRK2 Parkinson’s disease
Authors: Gonzalez-Hunt C. P. , Thacker E. A. , Toste C. M. , Boularand S. , Deprets S. , Dubois L. , Sanders L. H.
Published: October 2020

Leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for the treatment of Parkinson’s disease (PD) and LRRK2 kinase inhibitors are currently being tested in early phase clinical trials. In order to ensure the highest chance of success, a biomarker-guided entry into clinical trials is key. LRRK2 phosphorylation, and phosphorylation of the LRRK2 substrate Rab10, have been proposed as target engagement biomarkers for LRRK2 kinase inhibition. However, a pharmacodynamic biomarker to demonstrate that a biological response has occurred is lacking. We previously discovered that the LRRK2 G2019S mutation causes mitochondrial DNA (mtDNA) damage and is LRRK2 kinase activity-dependent. Here, we have explored the possibility that measurement of mtDNA damage is a “surrogate” for LRRK2 kinase activity and consequently of kinase inhibitor activity. Mitochondrial DNA damage was robustly increased in PD patient-derived immune cells with LRRK2 G2019S mutations as compared with controls. Following treatment with multiple classes of LRRK2 kinase inhibitors, a full reversal of mtDNA damage to healthy control levels was observed and correlated with measures of LRRK2 dephosphorylation. Taken together, assessment of mtDNA damage levels may be a sensitive measure of altered kinase activity and provide an extended profile of LRRK2 kinase modulation in clinical studies.
Design and in vivo evaluation of a microparticulate depot formulation of buprenorphine for veterinary use
Authors: Schreiner Viktoria , Durst Mattea , Arras Margarete , Detampel Pascal , Jirkof Paulin , Huwyler Jörg
Published: October 2020

Buprenorphine is a frequently used analgetic agent in veterinary medicine. A major drawback, however, is the short duration of action requiring several daily administrations. We therefore designed a poly-lactic-co-glycolic acid (PLGA) based microparticulate drug formulation for sustained parenteral drug release. Particles were designed to allow for a fast onset of action and a duration of the analgesic effect of at least two days in laboratory mice. Microparticles were produced using a solvent evaporation technique. Release rate was dependent on polymer type and particle size. Spherical particles used for subsequent animal studies had a mean size of 50 µm and contained 4.5% of buprenorphine. Drug release was characterized by an initial burst release of 30% followed by complete release over seven days. In vivo pharmacokinetic experiments in female C57BL/6 J mice confirmed prolonged exposure in plasma and brain tissue and correlated with the pharmacological effect in the hot plate assay or after minor abdominal surgery. No adverse side effects with respect to food and water intake, body weight, local tolerability, or nesting behavior were observed. Our formulation is an attractive alternative to established immediate release formulations. A use for prolonged pain management in laboratory animals is proposed.
A 1H-NMR approach to myocardial energetics
Authors: Heitzman Jackie A. , Dobratz Tyler C. , Fischer Kaleb D. , Townsend DeWayne
Published: October 2020

Understanding the energetic state of the heart is essential for unraveling the central tenets of cardiac physiology. The heart uses a tremendous amount of energy and reductions in that energy supply can have lethal consequences. While ischemic events clearly result in significant metabolic perturbations, heart failure with both preserved and reduced ejection fraction display reductions in energetic status. To date, most cardiac energetics have been performed using 31P-NMR, which requires dedicated access to a specialized NMR spectrometer. This has limited the availability of this method to a handful of centers around the world. Here we present a method of assessing myocardial energetics in the isolated mouse heart using 1H-NMR spectrometers that are widely available in NMR core facilities. In addition, this methodology provides information on many other important metabolites within the heart, including unique metabolic differences between the hypoxic and ischemic hearts. Furthermore, we demonstrate the correlation between myocardial energetics and measures of contractile function in the mouse heart. These methods will allow a broader examination of myocardial energetics providing a valuable tool to aid in the understanding of the nature of these energetic deficits and to develop therapies directed at improving myocardial energetics in failing hearts.
Discovering spatial interaction patterns of near repeat crime by spatial association rules mining
Authors: He Zhanjun , Tao Liufeng , Xie Zhong , Xu Chong
Published: October 2020

Urban crime incidents always exhibit a structure of spatio-temporal dependence. Exploration of the spatio-temporal interactions of crime incidents is critical to understanding the occurrence mechanism and spatial transmission characteristics of crime occurrences, therefore facilitating the determination of policing practices. Although previous researches have repeatedly demonstrated that the crime incidents are spatially clustered, the anisotropic characteristics of spatial interaction has not been fully considered and the detailed spatial transmission of crime incidents has rarely been explored. To better understand the spatio-temporal interaction patterns of crime occurrence, this study proposes a new spatial association mining approach to discover significant spatial transmission routes and related high flow regions. First, all near repeat crime pairs are identified based on spatio-temporal proximity. Then, these links between close pairs are simplified by spatial aggregation on spatial grids. Based on that, measures of the spatio-temporal interactions are defined and a spatial association pattern mining approach is developed to discover significant spatial interaction patterns. Finally, the relationship between significant spatial transmission patterns and road network structure is analyzed. The experimental results demonstrate that our approach is able to effectively discover spatial transmission patterns from massive crime incidents data. Our results are expected to provide effective guidance for crime pattern analysis and even crime prevention.
The impact of handling technique and handling frequency on laboratory mouse welfare is sex-specific
Authors: Sensini Federica , Inta Dragos , Palme Rupert , Brandwein Christiane , Pfeiffer Natascha , Riva Marco Andrea , Gass Peter , Mallien Anne Stephanie
Published: October 2020

Handling is a well-known source of stress to laboratory animals and can affect variability of results and even compromise animal welfare. The conventional tail handling in mice has been shown to induce aversion and anxiety-like behaviour. Recent findings demonstrate that the use of alternative handling techniques, e.g. tunnel handling, can mitigate negative handling-induced effects. Here, we show that technique and frequency of handling influence affective behaviour and stress hormone release of subjects in a sex-dependent manner. While frequent tail handling led to a reduction of wellbeing-associated burrowing and increased despair-like behaviour in male mice, females seemed unaffected. Instead, they displayed a stress response to a low handling frequency, which was not detectable in males. This could suggest that in terms of refinement, the impact in handling could differ between the sexes. Independently from this observation, both sexes preferred to interact with the tunnel. Mice generally explored the tunnel more often than the tail-handling hands of the experimenter and showed more positively rated approaches, e.g. touching or climbing, and at the same time, less defensive burrowing, indicating a strong preference for the tunnel.
Monitoring elasmobranch assemblages in a data-poor country from the Eastern Tropical Pacific using baited remote underwater video stations
Authors: Espinoza Mario , Araya-Arce Tatiana , Chaves-Zamora Isaac , Chinchilla Isaac , Cambra Marta
Published: October 2020

Understanding how threatened species are distributed in space and time can have direct applications to conservation planning. However, implementing standardized methods to monitor populations of wide-ranging species is often expensive and challenging. In this study, we used baited remote underwater video stations (BRUVS) to quantify elasmobranch abundance and distribution patterns across a gradient of protection in the Pacific waters of Costa Rica. Our BRUVS survey detected 29 species, which represents 54% of the entire elasmobranch diversity reported to date in shallow waters (< 60 m) of the Pacific of Costa Rica. Our data demonstrated that elasmobranchs benefit from no-take MPAs, yet large predators are relatively uncommon or absent from open-fishing sites. We showed that BRUVS are capable of providing fast and reliable estimates of the distribution and abundance of data-poor elasmobranch species over large spatial and temporal scales, and in doing so, they can provide critical information for detecting population-level changes in response to multiple threats such as overfishing, habitat degradation and climate change. Moreover, given that 66% of the species detected are threatened, a well-designed BRUVS survey may provide crucial population data for assessing the conservation status of elasmobranchs. These efforts led to the establishment of a national monitoring program focused on elasmobranchs and key marine megafauna that could guide monitoring efforts at a regional scale.
Removal of biogenic amines from wines by chemisorption on functionalized silica and effects on other wine components
Authors: Rodríguez-Bencomo Juan José , Rigou Peggy , Mattivi Fulvio , López Francisco , Mehdi Ahmad
Published: October 2020

The effectiveness of several functionalized silica materials (cation-exchange materials) for the removal of biogenic amines from wines, and the effects on other wine components and organoleptic characteristics were evaluated. Results have shown that mesoporous silica material bi-functionalized with phosphonic and sulfonic acids allowed the removal of histamine, putrescine, cadaverine, spermine and spermidine from wines, although the dose must be adapted for each wine according to the removal requirements and wine characteristics. A plus of the adsorbent developed is that it can be recovered and re-used for at least 3 treatments. Immediately following the treatments, a decrease in the levels of linear ethyl esters (ethyl hexanoate, ethyl octanoate and ethyl decanoate) was observed, although these levels were re-equilibrated after several days reducing this undesired side effect. A slight, but perceptible, effect on wine color was observed, probably due to the slight decrease in the pH of the wine produced by the treatments. On the basis of the sensory analysis that focused only on the aroma of the wines, the proposed technique would be more adequate for wines aged in barrels than for young wines.
Metabolic and physiological responses to progressive drought stress in bread wheat
Authors: Itam Michael , Mega Ryosuke , Tadano Shota , Abdelrahman Mostafa , Matsunaga Sachiko , Yamasaki Yuji , Akashi Kinya , Tsujimoto Hisashi
Published: October 2020

Wheat (Tritium aestivum) is vulnerable to future climate change because it is predominantly grown under rain-fed conditions in drought-prone areas. Thus, in-depth understanding of drought effect on wheat metabolism is essential for developing drought-tolerant wheat varieties. Here, we exposed wheat ‘Norin 61’ plants to progressive drought stress [0 (before drought), 2, 4, 6, 8, and 10 days after withholding water] during the flowering stage to investigate physiological and metabolomic responses. Transcriptional analyses of key abscisic acid-responsive genes indicated that abscisic acid signalling played a major role in the adaptation of wheat to water deficit. Carbon isotope composition had a higher value than the control while canopy temperature (CT) increased under drought stress. The CT depression was tightly correlated with soil water potential (SWP). Additionally, SWP at − 517 kPa was identified as the critical point for increasing CT and inducing reactive oxygen species. Metabolome analysis identified four potential drought-responsive biomarkers, the enhancement of nitrogen recycling through purine and pyrimidine metabolism, drought-induced senescence based on 1-aminocyclopropane-1-carboxylic acid and Asn accumulation, and an anti-senescence response through serotonin accumulation under severe drought stress. Our findings provide in-depth insight into molecular, physiological and metabolite changes involved in drought response which are useful for wheat breeding programs to develop drought-tolerant wheat varieties.
Effects of canopy midstory management and fuel moisture on wildfire behavior
Authors: Banerjee Tirtha , Heilman Warren , Goodrick Scott , Hiers J. Kevin , Linn Rod
Published: October 2020

Increasing trends in wildfire severity can partly be attributed to fire exclusion in the past century which led to higher fuel accumulation. Mechanical thinning and prescribed burns are effective techniques to manage fuel loads and to establish a higher degree of control over future fire risk, while restoring fire prone landscapes to their natural states of succession. However, given the complexity of interactions between fine scale fuel heterogeneity and wind, it is difficult to assess the success of thinning operations and prescribed burns. The present work addresses this issue systematically by simulating a simple fire line and propagating through a vegetative environment where the midstory has been cleared in different degrees, leading to a canopy with almost no midstory, another with a sparse midstory and another with a dense midstory. The simulations are conducted for these three canopies under two different conditions, where the fuel moisture is high and where it is low. These six sets of simulations show widely different fire behavior, in terms of fire intensity, spread rate and consumption. To understand the physical mechanisms that lead to these differences, detailed analyses are conducted to look at wind patterns, mean flow and turbulent fluxes of momentum and energy. The analyses also lead to improved understanding of processes leading to high intensity crowning behavior in presence of a dense midstory. Moreover, this work highlights the importance of considering fine scale fuel heterogeneity, seasonality, wind effects and the associated fire-canopy-atmosphere interactions while considering prescribed burns and forest management operations.
Effects of applying platelet-rich plasma during arthroscopic rotator cuff repair: a systematic review and meta-analysis of randomised controlled trials
Authors: Yang Fu-An , Liao Chun-De , Wu Chin-Wen , Shih Ya-Chu , Wu Lien-Chen , Chen Hung-Chou
Published: October 2020

Because of its healing properties, platelet-rich plasma (PRP) has been applied to the bone–tendon interface during arthroscopic rotator cuff repair to improve surgical outcomes. However, its effects remain ambiguous. Therefore, we conducted this systematic review and meta-analysis to assess the effects of PRP on retear rate and functional outcomes. Randomised control trials were identified and extracted. Data collection was completed on 15 February 2020. The results are expressed as the risk ratio (RR) for the categorical variables and weighted mean difference for the continuous variables, with 95% confidence intervals (CIs). Analyses were performed using RevMan 5.3 software. Seven randomised controlled trials published from 2013 to 2018, with 541 patients in total, were included. The results revealed a significant decrease in retear rate [RR 0.38, 95% CI (0.22, 0.68),P = 0.0009). Furthermore, a significant improvement was observed regarding short-term Constant score [mean difference = 3.28, 95% CI (1.46, 5.11),P = 0.0004), short-term University of California at Los Angeles activity score [mean difference = 1.60, 95% CI (0.79, 2.42),P = 0.0001], and short-term visual analogue scale score [mean difference =  − 0.14, 95% CI (− 0.23, − 0.05),P = 0.002]. This systematic review indicates the efficacy of PRP when applied to the bone–tendon interface during arthroscopic rotator cuff repair.
Sleeping late is a risk factor for myopia development amongst school-aged children in China
Authors: Liu Xiao Nicole , Naduvilath Thomas John , Wang Jingjing , Xiong Shuyu , He Xiangui , Xu Xun , Sankaridurg Padmaja R.
Published: October 2020

Myopia, a leading cause of distance vision impairment, is projected to affect half of the world’s population in 30 years. We analysed the relationship between certain demographic, environmental, and behavioural factors and myopia from a 2-year school-based, prospective trial conducted in Shanghai, China. This trial enrolled 6295 school-aged children at baseline and followed them up for 24 months. The relationship between abovementioned factors and myopia was examined and the role of sleep in childhood myopia development was highlighted. Our results suggest that ‘sleeping late’ is a risk factor for myopia prevalence at baseline (odds ratio [OR] = 1.55, p = 0.04), 2-year myopia incidence (odds ratio [OR] = 1.44, p = 0.02) and progression over 24 months (p = 0.005), after adjusting for residency area, age, gender, sleep duration, and time spent outdoors. The identification and consistency of results with late sleepers being a susceptible group to both myopia onset and progression suggests a complex relationship between circadian rhythm, indoor environment, habitual indoor activities and myopia development and progression. These results can offer new insights to future myopia aetiology studies as well as aid in decision-making of myopia prevention strategies.
Application of small molecule FPR1 antagonists in the treatment of cancers
Authors: Ahmet Djevdet S. , Basheer Haneen A. , Salem Anwar , Lu Di , Aghamohammadi Amin , Weyerhäuser Patrick , Bordiga Andrea , Almeniawi Juman , Rashid Sabah , Cooper Patricia A. , Shnyder Steven D. , Vinader Victoria , Afarinkia Kamyar
Published: October 2020

The formylpeptide receptor-1 (FPR1) is a member of the chemotactic GPCR-7TM formyl peptide receptor family, whose principle function is in trafficking of various leukocytes into sites of bacterial infection and inflammation. More recently, FPR1 has been shown to be expressed in different types of cancer and in this context, plays a significant role in their expansion, resistance and recurrence. ICT12035 is a selective and potent (30 nM in calcium mobilisation assay) small molecule FPR1 antagonist. Here, we demonstrate the efficacy of ICT12035, in a number of 2D and 3D proliferation and invasion in vitro assays and an in vivo model. Our results demonstrate that targeting FPR1 by a selective small molecule antagonist, such as ICT12035, can provide a new avenue for the treatment of cancers.
Random-telegraph-noise-enabled true random number generator for hardware security
Authors: Brown James , Zhang Jian Fu , Zhou Bo , Mehedi Mehzabeen , Freitas Pedro , Marsland John , Ji Zhigang
Published: October 2020

The future security of Internet of Things is a key concern in the cyber-security field. One of the key issues is the ability to generate random numbers with strict power and area constrains. “True Random Number Generators” have been presented as a potential solution to this problem but improvements in output bit rate, power consumption, and design complexity must be made. In this work we present a novel and experimentally verified “True Random Number Generator” that uses exclusively conventional CMOS technology as well as offering key improvements over previous designs in complexity, output bitrate, and power consumption. It uses the inherent randomness of telegraph noise in the channel current of a single CMOS transistor as an entropy source. For the first time multi-level and abnormal telegraph noise can be utilised, which greatly reduces device selectivity and offers much greater bitrates. The design is verified using a breadboard and FPGA proof of concept circuit and passes all 15 of the NIST randomness tests without any need for post-processing of the generated bitstream. The design also shows resilience against machine learning attacks performed by the LSTM neural network.
Particle packing into loose networks for tough and sticky composite gels
Authors: Asoh Taka-Aki , Yamamoto Tatsuya , Uyama Hiroshi
Published: October 2020

Hydrogel is an attractive material, but its application is limited due to its low mechanical strength. In this study, a tough composite gel could be prepared by synthesizing polymer particles within a polymer network having relatively loose cross-linking. Since the polymer network acts as a dispersion stabilizer during the synthesis of the hydrophobic polymer particles, a large amount of particles could be introduced into the gel without agglomeration. It was suggested that the high level of toughness was induced by the adsorption and desorption of the polymer chains on the surface of the finely packed particles. By using a stimuli-responsive polymer network, elasticity and plasticity of composite gels could be controlled in response to external stimuli, and adhesion on the gel surface could also be modulated.
RETRACTED ARTICLE: RNA editing of BFP, a point mutant of GFP, using artificial APOBEC1 deaminase to restore the genetic code
Authors: Bhakta Sonali , Sakari Matomo , Tsukahara Toshifumi
Published: October 2020

Many genetic diseases are caused by T-to-C point mutations. Hence, editing of mutated genes represents a promising strategy for treating these disorders. We engineered an artificial RNA editase by combining the deaminase domain of APOBEC1 (apolipoprotein B mRNA editing catalytic polypeptide 1) with a guideRNA (gRNA) which is complementary to target mRNA. In this artificial enzyme system, gRNA is bound to MS2 stem-loop, and deaminase domain, which has the ability to convert mutated target nucleotide C-to-U, is fused to MS2 coat protein. As a target RNA, we used RNA encoding blue fluorescent protein (BFP) which was derived from the gene encoding GFP by 199 T > C mutation. Upon transient expression of both components (deaminase and gRNA), we observed GFP by confocal microscopy, indicating that mutated 199C in BFP had been converted to U, restoring original sequence of GFP. This result was confirmed by PCR–RFLP and Sanger’s sequencing using cDNA from transfected cells, revealing an editing efficiency of approximately 21%. Although deep RNA sequencing result showed some off-target editing events in this system, we successfully developed an artificial RNA editing system using artificial deaminase (APOBEC1) in combination with MS2 system could lead to therapies that treat genetic disease by restoring wild-type sequence at the mRNA level.
Cloning and activity analysis of the promoter of nucleotide exchange factor gene ZjFes1 from the seagrasses Zostera japonica
Authors: Chen Siting , Qiu Guanglong
Published: October 2020

After HSP70 binds to the J domain of the substrate and co-chaperone protein, ATP is hydrolyzed to ADP, and the nucleotide exchange factors (NEFs) promote the release of ADP. Under physiological conditions, the nucleotide exchange step is the rate-limiting step, which is accelerated by NEFs. In this study, the promoter of nucleotide exchange factor ZjFes1 was cloned, and its expression in tissues and under heat stress was studied to understand the regulatory mechanism of ZjFes1 and provide the molecular basis to study heat tolerance mechanism of seagrass. It was found that the promoter has common cis-acting elements in promoter and enhancer regions CAAT-box, as well as light response elements AE-box, Box 4 and TCCC-motif, a cis-acting regulatory element essential for the anaerobic induction of ARE, hormone response elements CGTCA-motif and TGACG-motif (MeJA response element), GARE-motif (gibberellin response element), TGA-element (auxin response element), a cis-acting regulatory element related to meristem expression CAT-box, and a cis-acting element involved in defense and stress responsiveness of TC-rich repeats. Two-week-old seedlings exhibited weak GUS activities in their cotyledons. In addition, the AtFes1A promoter was constitutively active in the anthers. After exposure to 38 °C for 2 h, the root tips of two-week-old seedlings were stained a strong blue. Heat-inducible activities of GUS were also observed in the cotyledons, roots, leaves, anthers, sepals and siliques.