bluuebunny/crossref_metadata_2025 huggingface dataset:
Choline Catabolism in Burkholderia thailandensis Is Regulated by Multiple Glutamine Amidotransferase 1-Containing AraC Family Transcriptional Regulators
Authors: Nock Adam M. , Wargo Matthew J.
Published: July 2016

Burkholderia thailandensis
is a soil-dwelling bacterium that shares many metabolic pathways with the ecologically similar, but evolutionarily distant,
Pseudomonas aeruginosa
. Among the diverse nutrients it can utilize is choline, metabolizable to the osmoprotectant glycine betaine and subsequently catabolized as a source of carbon and nitrogen, similar to
P. aeruginosa
. Orthologs of genes in the choline catabolic pathway in these two bacteria showed distinct differences in gene arrangement as well as an additional orthologous transcriptional regulator in
B. thailandensis
. In this study, we showed that multiple glutamine amidotransferase 1 (GATase 1)-containing AraC family transcription regulators (GATRs) are involved in regulation of the
B. thailandensis
choline catabolic pathway (
gbdR1
,
gbdR2
, and
souR
). Using genetic analyses and sequencing the transcriptome in the presence and absence of choline, we identified the likely regulons of
gbdR1
(
BTH_II1869
) and
gbdR2
(
BTH_II0968
). We also identified a functional ortholog for
P. aeruginosa
souR
, a GATR that regulates the metabolism of sarcosine to glycine. GbdR1 is absolutely required for expression of the choline catabolic locus, similar to
P. aeruginosa
GbdR, while GbdR2 is important to increase expression of the catabolic locus. Additionally, the
B. thailandensis
SouR ortholog (
BTH_II0994
) is required for catabolism of choline and its metabolites as carbon sources, whereas in
P. aeruginosa
, SouR function can by bypassed by GbdR. The strategy employed by
B. thailandensis
represents a distinct regulatory solution to control choline catabolism and thus provides both an evolutionary counterpoint and an experimental system to analyze the acquisition and regulation of this pathway during environmental growth and infection.

IMPORTANCE
Many proteobacteria that occupy similar environmental niches have horizontally acquired orthologous genes for metabolism of compounds useful in their shared environment. The arrangement and differential regulation of these components can help us understand both the evolution of these systems and the potential roles these pathways have in the biology of each bacterium. Here, we describe the transcriptome response of
Burkholderia thailandensis
to the eukaryote-enriched molecule choline, identify the regulatory pathway governing choline catabolism, and compare the pathway to that previously described for
Pseudomonas aeruginosa
. These data support a multitiered regulatory network in
B. thailandensis
, with conserved orthologs in the select agents
Burkholderia pseudomallei
and
Burkholderia mallei
, as well as the opportunistic lung pathogens in the
Burkholderia cepacia
clade.
Reconstitution and Minimization of a Micrococcin Biosynthetic Pathway in Bacillus subtilis
Authors: Bennallack Philip R. , Bewley Kathryn D. , Burlingame Mark A. , Robison Richard A. , Miller Susan M. , Griffitts Joel S.
Published: July 2016

Thiopeptides represent one of several families of highly modified peptide antibiotics that hold great promise for natural product engineering. These macrocyclic peptides are produced by a combination of ribosomal synthesis and extensive posttranslational modification by dedicated processing enzymes. We previously identified a compact, plasmid-borne gene cluster for the biosynthesis of micrococcin P1 (MP1), an archetypal thiopeptide antibiotic. In an effort to genetically dissect this pathway, we have reconstituted it in
Bacillus subtilis
. Successful MP1 production required promoter engineering and the reassembly of essential biosynthetic genes in a modular plasmid. The resulting system allows for rapid pathway manipulation, including protein tagging and gene deletion. We find that 8 processing proteins are sufficient for the production of MP1 and that the tailoring enzyme TclS catalyzes a C-terminal reduction step that distinguishes MP1 from its sister compound micrococcin P2.

IMPORTANCE
The emergence of antibiotic resistance is one of the most urgent human health concerns of our day. A crucial component in an integrated strategy for countering antibiotic resistance is the ability to engineer pathways for the biosynthesis of natural and derivatized antimicrobial compounds. In this study, the model organism
B. subtilis
was employed to reconstitute and genetically modularize a 9-gene system for the biosynthesis of micrococcin, the founding member of a growing family of thiopeptide antibiotics.
Single-Stranded DNA Uptake during Gonococcal Transformation
Authors: Hepp Christof , Gangel Heike , Henseler Katja , Günther Niklas , Maier Berenike
Published: July 2016

Neisseria gonorrhoeae
is naturally competent for transformation. The first step of the transformation process is the uptake of DNA from the environment into the cell. This transport step is driven by a powerful molecular machine. Here, we addressed the question whether this machine imports single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) at similar rates. The fluorescence signal associated with the uptake of short DNA fragments labeled with a single fluorescent marker molecule was quantified. We found that ssDNA with a double-stranded DNA uptake sequence (DUS) was taken up with a similar efficiency as dsDNA. Imported ssDNA was degraded rapidly, and the thermonuclease Nuc was required for degradation. In a
nuc
deletion background, dsDNA and ssDNA with a double-stranded DUS were imported and used as the substrates for transformation, whereas the import and transformation efficiencies of ssDNA with single-stranded DUS were below the detection limits. We conclude that the DNA uptake machine requires a double-stranded DUS for efficient DNA recognition and transports ssDNA and dsDNA with comparable efficiencies.

IMPORTANCE
Bacterial transformation enables bacteria to exchange genetic information. It can speed up adaptive evolution and enhances the potential of DNA repair. The transport of DNA through the outer membrane is the first step of transformation in Gram-negative species. It is driven by a powerful molecular machine whose mechanism remains elusive. Here, we show for
Neisseria gonorrhoeae
that the machine transports single- and double-stranded DNA at comparable rates, provided that the species-specific DNA uptake sequence is double stranded. Moreover, we found that single-stranded DNA taken up into the periplasm is rapidly degraded by the thermonuclease Nuc. We conclude that the secondary structure of transforming DNA is important for the recognition of self DNA but not for the process of transport through the outer membrane.
Experimental Analysis of Functional Variation within Protein Families: Receiver Domain Autodephosphorylation Kinetics
Authors: Page Stephani C. , Immormino Robert M. , Miller Thane H. , Bourret Robert B.
Published: July 2016

Plants and microorganisms use two-component signal transduction systems (TCSs) to mediate responses to environmental stimuli. TCSs mediate responses through phosphotransfer from a conserved histidine on a sensor kinase to a conserved aspartate on the receiver domain of a response regulator. Typically, signal termination occurs through dephosphorylation of the receiver domain, which can catalyze its own dephosphorylation. Despite strong structural conservation between receiver domains, reported autodephosphorylation rate constants (
k
dephos
) span a millionfold range. Variable receiver domain active-site residues D + 2 and T + 2 (two amino acids C terminal to conserved phosphorylation site and Thr/Ser, respectively) influence
k
dephos
values, but the extent and mechanism of influence are unclear. We used sequence analysis of a large database of naturally occurring receiver domains to design mutant receiver domains for experimental analysis of autodephosphorylation kinetics. When combined with previous analyses,
k
dephos
values were obtained for CheY variants that contained D + 2/T + 2 pairs found in 54% of receiver domain sequences. Tested pairs of amino acids at D + 2/T + 2 generally had similar effects on
k
dephos
in CheY, PhoB
N
, or Spo0F. Acid or amide residues at D + 2/T + 2 enhanced
k
dephos
. CheY variants altered at D + 2/T + 2 exhibited rate constants for autophosphorylation with phosphoramidates and autodephosphorylation that were inversely correlated, suggesting that D + 2/T + 2 residues interact with aspects of the ground or transition states that differ between the two reactions.
k
dephos
of CheY variants altered at D + 2/T + 2 correlated significantly with
k
dephos
of wild-type receiver domains containing the same D + 2/T + 2 pair. Additionally, particular D + 2/T + 2 pairs were enriched in different response regulator subfamilies, suggesting functional significance.

IMPORTANCE
One protein family, defined by a conserved domain, can include hundreds of thousands of known members. Characterizing conserved residues within a conserved domain can identify functions shared by all family members. However, a general strategy to assess features that differ between members of a family is lacking. Fully exploring the impact of just two variable positions within a conserved domain could require assessment of 400 (i.e., 20 × 20) variants. Instead, we created and analyzed a nonredundant database of receiver domain sequences. Five percent of D + 2/T + 2 pairs were sufficient to represent 50% of receiver domain sequences. Using protein sequence analysis to prioritize mutant choice made it experimentally feasible to extensively probe the influence of positions D + 2 and T + 2 on receiver domain autodephosphorylation kinetics.
JC Polyomavirus Infection of Primary Human Renal Epithelial Cells Is Controlled by a Type I IFN-Induced Response
Authors: Assetta Benedetta , De Cecco Marco , O’Hara Bethany , Atwood Walter J.
Published: July 2016

The JC and BK human polyomaviruses (JCPyV and BKPyV, respectively) establish lifelong persistent infections in the kidney. In immunosuppressed individuals, JCPyV causes progressive multifocal leukoencephalopathy (PML), a fatal neurodegenerative disease, and BKPyV causes polyomavirus-associated nephropathy (PVN). In this study, we compared JCPyV and BKPyV infections in primary human renal proximal tubule epithelial (HRPTE) cells. JCPyV established a persistent infection, but BKPyV killed the cells in 15 days. To identify the cellular factors responsible for controlling JCPyV infection and promoting viral persistence, we profiled the transcriptomes of JCPyV- and BKPyV-infected cells at several time points postinfection. We found that infection with both viruses induced interferon production but that interferon-stimulated genes (ISGs) were only activated in the JCPyV-infected cells. Phosphorylated STAT1 and IRF9, which are responsible for inducing ISGs, translocated to the nucleus of JCPyV-infected cells but did not in BKPyV-infected cells. In BKPyV-infected cells, two critical suppressors of cytokine signaling, SOCS3 and SOCS1, were induced. Infection with BKPyV but not JCPyV caused reorganization of PML bodies that are associated with inactivating antiviral responses. Blockade of the interferon receptor and neutralization of soluble interferon alpha (IFN-α) and IFN-β partially alleviated the block to JCPyV infection, leading to enhanced infectivity. Our results show that a type I IFN response contributes to the establishment of persistent infection by JCPyV in HRPTE cells.

IMPORTANCE
The human polyomaviruses JCPyV and BKPyV both establish lifelong persistent infection in the kidneys. In immunosuppressed patients, BKPyV causes significant pathology in the kidney, but JCPyV is only rarely associated with disease in this organ. The reasons behind this striking difference in kidney pathology are unknown. In this study, we show that infection of primary human renal tubule epithelial cells with JCPyV and BKPyV results in divergent innate immune responses that control JCPyV but fail to control BKPyV. This is the first study that directly compares JCPyV and BKPyV infection
in vitro
in the same cell type they naturally infect, and the significant differences that have been uncovered could in part explain the distinct disease outcomes.
Interaction of Resistance Training, Electroacupuncture and Huang Qi supplementation on skeletal muscle function and GLUT4 protein concentration in rats
Authors: Lee Sukho , Kim Kijeong , Lambrecht Nathalie J , Hong Junyoung , Liao Yi-Hung , Yoon Aram , Bernard Jeffrey R
Published: July 2016

Objective

To determine the effects and potential synergy of resistance training (RT), Huang Qi (HQ) herbal supplementation, and electroacupuncture (EA) on skeletal muscle mass, contractile properties, and components of the insulin signalling pathway in healthy Sprague Dawley rats.

Methods

Female Sprague Dawley rats were randomly assigned to one of five groups (n=8 each): control (CON), RT only, RT with EA (RT-EA), RT with HQ (RT-HQ), and RT combined with both EA and HQ (RT-EA-HQ). RT was performed using ladder climbing every other day for 8 weeks. Sparse-wave EA was applied for 15 min/day, 3 times/week for 8 weeks. HQ supplementation was provided via oral gavage daily for 8 weeks.

Results

RT significantly increased the muscle mass of the flexor hallucis longus (FHL) compared to CON. The isometric twitch and tetanic tension of the FHL in the RT-EA, RT-HQ, and RT-EA-HQ groups were significantly higher compared to CON and RT groups. RT-EA treatment (with or without HQ) significantly increased GLUT4 protein concentration but had no impact on Akt-2.

Conclusions

EA appears to be an effective treatment modality for increasing muscle mass and function when combined with RT. RT-EA may also be an effective method for improving glucose tolerance as a result of increases in GLUT4 protein concentration.
Validation of a portable, deployable system for continuous vital sign monitoring using a multiparametric wearable sensor and personalised analytics in an Ebola treatment centre
Authors: Steinhubl Steven R , Feye Dawit , Levine Adam C , Conkright Chad , Wegerich Stephan W , Conkright Gary
Published: July 2016

Background

The recent Ebola epidemic in West Africa strained existing healthcare systems well beyond their capacities due to the extreme volume and severity of illness of the patients. The implementation of innovative digital technologies within available care centres could potentially improve patient care as well as healthcare worker safety and effectiveness.

Methods

We developed a Modular Wireless Patient Monitoring System (MWPMS) and conducted a proof of concept study in an Ebola treatment centre (ETC) in Makeni, Sierra Leone. The system was built around a wireless, multiparametric ‘band-aid’ patch sensor for continuous vital sign monitoring and transmission, plus sophisticated data analytics. Results were used to develop personalised analytics to support automated alerting of early changes in patient status.

Results

During the 3-week study period, all eligible patients (n=26) admitted to the ETC were enrolled in the study, generating a total of 1838 hours of continuous vital sign data (mean of 67.8 hours/patient), including heart rate, heart rate variability, activity, respiratory rate, pulse transit time (inversely related to blood pressure), uncalibrated skin temperature and posture. All patients tolerated the patch sensor without problems. Manually determined and automated vital signs were well correlated. Algorithm-generated Multivariate Change Index, pulse transit time and arrhythmia burden demonstrated encouraging preliminary findings of important physiological changes, as did ECG waveform changes.

Conclusions

In this proof of concept study, we were able to demonstrate that a portable, deployable system for continuous vital sign monitoring via a wireless, wearable sensor supported by a sophisticated, personalised analytics platform can provide high-acuity monitoring with a continuous, objective measure of physiological status of all patients that is achievable in virtually any healthcare setting, anywhere in the world.
What are the factors associated with good mental health among Aboriginal children in urban New South Wales, Australia? Phase I findings from the Study of Environment on Aboriginal Resilience and Child Health (SEARCH)
Authors: Williamson Anna , D'Este Catherine , Clapham Kathleen , Redman Sally , Manton Toni , Eades Sandra , Schuster Leanne , Raphael Beverley
Published: July 2016

Objective

To identify the factors associated with ‘good’ mental health among Aboriginal children living in urban communities in New South Wales, Australia.

Design

Cross-sectional survey (phase I of a longitudinal study).

Setting

4 Aboriginal Community Controlled Health Services that deliver primary care. All services were located in urban communities in New South Wales, Australia.

Participants

1005 Aboriginal children aged 4–17 years who participated in phase I of the Study of Environment on Aboriginal Resilience and Child Health (SEARCH).

Primary outcome measure

Carer report version of the Strengths and Difficulties Questionnaire. Scores <17 were considered to indicate ‘good’ mental health for the purposes of this article.

Results

The majority (72%) of SEARCH participants were not at high risk for emotional or behavioural problems. After adjusting for the relative contributions of significant demographic, child and carer health factors, the factors associated with good mental health among SEARCH children were having a carer who was not highly psychologically distressed (OR=2.8, 95% CI 1.6 to 5.1); not suffering from frequent chest, gastrointestinal or skin infections (OR=2.8, 95% CI 1.8 to 4.3); and eating two or more servings of vegetables per day (OR=2.1, 95% CI 1.2 to 3.8). Being raised by a foster carer (OR=0.2, 95% CI 0.01 to 0.71) and having lived in 4 or more homes since birth (OR=0.62, 95% CI 0.39 to 1.0) were associated with significantly lower odds of good mental health. Slightly different patterns of results were noted for adolescents than younger children.

Conclusions

Most children who participated in SEARCH were not at high risk for emotional or behavioural problems. Promising targets for efforts to promote mental health among urban Aboriginal children may include the timely provision of medical care for children and provision of additional support for parents and carers experiencing mental or physical health problems, for adolescent boys and for young people in the foster care system.
Protocol of the Australasian Malignant Pleural Effusion-2 (AMPLE-2) trial: a multicentre randomised study of aggressive versus symptom-guided drainage via indwelling pleural catheters
Authors: Azzopardi Maree , Thomas Rajesh , Muruganandan Sanjeevan , Lam David C L , Garske Luke A , Kwan Benjamin C H , Rashid Ali Muhammad Redzwan S , Nguyen Phan T , Yap Elaine , Horwood Fiona C , Ritchie Alexander J , Bint Michael , Tobin Claire L , Shrestha Ranjan , Piccolo Francesco , De Chaneet Christian C , Creaney Jenette , Newton Robert U , Hendrie Delia , Murray Kevin , Read Catherine A , Feller-Kopman David , Maskell Nick A , Lee Y C Gary
Published: July 2016

Introduction

Malignant pleural effusions (MPEs) can complicate most cancers, causing dyspnoea and impairing quality of life (QoL). Indwelling pleural catheters (IPCs) are a novel management approach allowing ambulatory fluid drainage and are increasingly used as an alternative to pleurodesis. IPC drainage approaches vary greatly between centres. Some advocate aggressive (usually daily) removal of fluid to provide best symptom control and chance of spontaneous pleurodesis. Daily drainages however demand considerably more resources and may increase risks of complications. Others believe that MPE care is palliative and drainage should be performed only when patients become symptomatic (often weekly to monthly). Identifying the best drainage approach will optimise patient care and healthcare resource utilisation.

Methods and analysis

A multicentre, open-label randomised trial. Patients with MPE will be randomised 1:1 to daily or symptom-guided drainage regimes after IPC insertion. Patient allocation to groups will be stratified for the cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group status 0–1 vs ≥2), presence of trapped lung (vs not) and prior pleurodesis (vs not). The primary outcome is the mean daily dyspnoea score, measured by a 100 mm visual analogue scale (VAS) over the first 60 days. Secondary outcomes include benefits on physical activity levels, rate of spontaneous pleurodesis, complications, hospital admission days, healthcare costs and QoL measures. Enrolment of 86 participants will detect a mean difference of VAS score of 14 mm between the treatment arms (5% significance, 90% power) assuming a common between-group SD of 18.9 mm and a 10% lost to follow-up rate.

Ethics and dissemination

The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study (number 2015-043). Results will be published in peer-reviewed journals and presented at scientific meetings.

Trial registration number

ACTRN12615000963527; Pre-results.
Association between psychological distress and dietary intake among evacuees after the Great East Japan Earthquake in a cross-sectional study: the Fukushima Health Management Survey
Authors: Uemura Mayu , Ohira Tetsuya , Yasumura Seiji , Otsuru Akira , Maeda Masaharu , Harigane Mayumi , Horikoshi Naoko , Suzuki Yuriko , Yabe Hirooki , Takahashi Hideto , Nagai Masato , Nakano Hironori , Zhang Wen , Hirosaki Mayumi , Abe Masafumi
Published: July 2016

Objective

Psychological distress is generally associated with poor dietary intake, but this has never been investigated among residents after a major disaster. We attempted to reveal the associations between dietary intake and non-specific mental health distress as well as traumatic symptoms among evacuees after the Great East Japan Earthquake of 2011.

Methods

In this cross-sectional analysis of 63 047 evacuees (27 901 men, 35 146 women) who responded to The Fukushima Health Management Survey in 2012, non-specific mental health distress was assessed using the Kessler-6 (K6) scale, while traumatic symptoms were evaluated using the Post-traumatic Stress Disorder (PTSD) Checklist—Stressor-Specific Version (PCL-S). The outcome was ‘low frequency’—meaning a daily consumption in the 25th centile or less according to the food frequency questionnaire (FFQ)—of 19 targeted food items. Logistic regression analysis was used to estimate ORs and 95% CIs adjusted for demographic, lifestyle-related and disaster-related factors.

Results

Of the participants, 14.7% suffered non-specific mental health distress, and 21.2% exhibited traumatic symptoms. Multivariable adjusted logistic regression analysis showed that the former were likely to have a low intake frequency of certain foods, such as rice and bread, fish, meat, vegetables or fruit (non-juice), soya bean products, milk, and yogurt or lactobacillus drinks; the latter were also likely to have a low intake frequency of certain foods, including rice and bread, fish, meat, vegetables (non-juice), milk and yogurt or lactobacillus drinks, but conversely consumed vegetable and fruit juices more often. These associations between dietary intake and non-specific mental health distress, as well as traumatic symptoms, were predominantly observed in women.

Conclusions

Psychological distress after the Great East Japan Earthquake among evacuees was associated with a low intake frequency of certain foods, and the association was predominantly observed in women.
Identifying process and outcome indicators of successful transitions from child to adult mental health services: protocol for a scoping review
Authors: Cleverley Kristin , Bennett Kathryn , Jeffs Lianne
Published: July 2016

Introduction

A significant proportion of youth need to transition from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS); however, the transition process is not well understood and often experienced poorly by youth. In the effort to design and evaluate standards of practice for transitions, there is a need to identify key elements of a successful transition. The objectives of this scoping review are to: (1) identify definitions of successful transitions from CAMHS to AMHS; and (2) identify indicators that have been used to measure CAMHS–AMHS transition care processes and quality, and outcomes.

Methods

We will search 8 electronic bibliographic databases from 1980 to 2016 (eg, Medline, EMBASE, PsycINFO), professional associations, policy documents, and other grey literature to identify relevant material. We will include experimental, quasi-experimental, observational studies, and non-research studies (guidelines, narrative reviews, policy documents) examining the transition from CAMHS to AMHS. 2 raters will independently screen each retrieved title and abstract for eligibility using the study inclusion criteria (level 1), and then will independently assess full-text articles to determine if these meet the inclusion criteria (level 2). Data extraction will be completed and results will be synthesised both quantitatively and qualitatively.

Ethics and dissemination

The results of the scoping review will be used to develop a set of indicators that will be prioritised and evaluated in a Delphi consensus study. This will serve as a foundation for the development of the first instrument to assess the quality and success of CAMHS–AMHS transitions. Ethics approval is not required for this scoping study.
CosPA 2015 and the Standard Model
Authors: Pauchy Hwang W.-Y.
Published: July 2016

In this keynote speech, I describe briefly “The Universe”, a journal/newsletter launched by APCosPA Organization, and my lifetime research on the Standard Model of particle physics. In this 21st Century, we should declare that we live in the quantum 4-dimensional Minkowski space-time with the force-fields gauge-group structure [Formula: see text] built-in from the very beginning. This background can see the lepton world, of atomic sizes, and offers us the eyes to see other things. It also can see the quark world, of the Fermi sizes, and this fact makes this entire world much more interesting.
The South Pole Telescope: Unraveling the Mystery of Dark Energy
Authors: Reichardt Christian L. , de Haan Tijmen , Bleem Lindsey E.
Published: July 2016

The South Pole Telescope (SPT) is a 10-meter telescope designed to survey the millimeter-wave sky, taking advantage of the exceptional observing conditions at the Amundsen-Scott South Pole Station. The telescope and its ground-breaking 960-element bolometric camera finished surveying 2500 square degrees at 95. 150, and 220 GHz in November 2011. We have discovered hundreds of galaxy clusters in the SPT-SZ survey through the Sunyaev-Zel’dovich (SZ) effect. The formation of galaxy clusters the largest bound objects in the universe is highly sensitive to dark energy and the history of structure formation. I will discuss the cosmological constraints from the SPT-SZ galaxy cluster sample as well as future prospects with the soon to-be-installed SPT-3G camera.
Will Quantum Cosmology Resurrect Chaotic Inflation Model?
Authors: Kim Sang Pyo , Kim Won
Published: July 2016

The single field chaotic inflation model with a monomial power greater than one seems to be ruled out by the recent Planck and WMAP CMB data while Starobinsky model with a higher curvature term seems to be a viable model. Higher curvature terms being originated from quantum fluctuations, we revisit the quantum cosmology of the Wheeler-DeWitt equation for the chaotic inflation model. The semiclassical cosmology emerges from quantum cosmology with fluctuations of spacetimes and matter when the wave function is peaked around the semiclassical trajectory with quantum corrections a la the de Broglie-Bohm pilot theory.
Verteporfin can Reverse the Paclitaxel Resistance Induced by YAP Over-Expression in HCT-8/T Cells without Photoactivation through Inhibiting YAP Expression
Authors: Pan Wang , Wang Qian , Zhang Yi , Zhang Naishu , Qin Jiamin , Li Wei , Wang Jing , Wu Fangfang , Cao Lingsen , Xu Guanglin
Published: July 2016

Background/Aims: Paclitaxel (PTX) is one of the most effective anti-cancer drugs. However, multiple drug resistance is still the main factor that hinders the effective treatment of cancer with PTX. Several factors including YAP over-expression can cause PTX resistance. In this study, we aimed to verify the role YAP plays in PTX resistance, explore the reversal of PTX resistance by verteporfin (VP) and investigate the effect of combination therapy of PTX and VP on the PTX resistant colon cancer cells (HCT-8/T). Methods: To study the relationship between YAP and PTX resistance, a stable YAP-over-expression or YAP silencing cell line was generated by transfected with YAP-plasmids or siYAP-RNA. WST-1 assay was performed to detect the cytotoxicity of PTX on HCT-8 and HCT-8/T cells. Clone formation assay and Transwell assay was preformed to determine the cell proliferation and invasion ability respectively. Immunofluorescence and Western blot analysis was performed for protein detection. Results: YAP was stronger expressed in HCT-8/T than in HCT-8, and PTX resistance was positively correlated with the level of YAP expression. VP, a strongly YAP inhibitor, could reduce the PTX resistance on HCT-8/T cells without light activation by inhibiting YAP. Beside, VP and PTX combination therapy showed synergism on inhibition of YAP and cytotoxicity to HCT-8/T. Moreover, verteporfin and PTX combination therapy affect the invasion and colony formation ability and induce apoptosis of HCT-8/T cells. Conclusions: VP can reverse the PTX resistance induced by YAP over-expression in HCT-8/T cells without photoactivation through inhibiting YAP expression.
Terminalia Chebulanin Attenuates Psoriatic Skin Lesion via Regulation of Heme Oxygenase-1
Authors: An Jingang , Li Tian , Dong Yingying , Li Zhengxiao , Huo Jia
Published: July 2016

Background/Aims: Psoriasis is one of the most common inflammatory skin disorders, affecting 3% of the general population. Terminalia chebulanin (TC) is a polyphenolic compound that possesses antioxidant and anti-inflammatory activities. The current study was designed to investigate the effect of TC on psoriatic lesions. Methods: We examined the protective effect of TC against psoriatic lesions in mice and keratinocyte proliferation in HaCaT cells. Results: We found that TC exhibited potent anti-psoriatic activities, as evidenced by improvement of erythema and scaling scores, decrease of epidermal, ear and skinfold thickening, decrease of tumor necrosis factor α (TNFα), interleukin (IL)-17A, IL-23 and matrix metalloproteinase (MMP)-9 expression, and decrease of TBARS content and increase of GSH content in IMQ-treated mice, and decrease of keratinocyte proliferation, TNFα, IL-17A and IL-23 expression, and ROS level in M5-treated cells. All those effects induced by TC were inhibited by zinc protoporphyrin IX (ZnPP), an inhibitor of heme oxygenase (HO)-1, indicating that HO-1 was responsible the anti-psoriatic effect of TC. Moreover, TC inhibited the upregulation of p65 NF-κB under in vitro psoriatic condition. ZnPP suppressed TC-induced inhibition of p65 NF-κB expression. Overexpression of p65 NF-κB significantly suppressed TC-induced decrease of TNFα, IL-17A and IL-23 expression and keratinocyte proliferation, indicating that HO-1-mediated downregulation of NF-κB was involved in the anti-psoriatic effect of TC. Conclusions: The data demonstrate that TC may serve as a potential therapeutic option for psoriatic patients.
Natural Killer Cell Deficits Aggravate Allergic Rhinosinusitis in a Murine Model
Authors: Kim Ji Heui , Gong Chang-Hoong , Choi Go Eun , Kim Sun A. , Kim Hun Sik , Jang Yong Ju
Published: July 2016

Objective: Defective innate immune functions can contribute to chronic rhinosinusitis (RS). Recently, it has been reported that chronic RS patients show impaired function of natural killer (NK) cells. We investigated the role of NK cells in eosinophilic inflammation in an allergic RS mouse model. Methods: Mice sensitized to ovalbumin (OVA) by intraperitoneal injection received nasal challenges with OVA for 5 weeks. NK cell depletion was achieved by intraperitoneal injections of anti-asialo ganglio-N-tetraosylceramide (ASGM1) antibodies 10 days before OVA sensitization and every 5 days thereafter until sacrifice. Sinonasal complex samples were evaluated histologically, and IL-4, IL-5, IL-13, IFN-γ, MIP-2, and eotaxin levels were measured in the nasal lavage fluid. Differential white blood cell counts were also obtained. Results: Allergic RS mice showed significantly more eosinophilic inflammation in the sinonasal mucosa, elevated levels of IL-4, IL-5, IL-13, and eotaxin in the nasal lavage fluid, and peripheral blood eosinophilia compared to control mice. The depletion of NK cells by anti-ASGM1 treatment induced more prominent eosinophilic inflammation and increased secretion of IL-5 and peripheral blood eosinophilia in allergic RS mice. Conclusion: The depletion of NK cells aggravates allergen-induced sinonasal eosinophilic inflammation, suggesting that impaired NK cell activity may be an exacerbating factor in eosinophilic chronic RS.
Thrombotic Events in Asymptomatic FXII Deficiency versus Symptomatic FXI Deficiency: Surprising Observations
Authors: Girolami A. , Cosi E. , Santarossa C. , Ferrari S. , Lombardi A.M.
Published: July 2016

Objective: To evaluate the impact of an asymptomatic congenital clotting defect (FXII deficiency) versus that of a similar but symptomatic defect (FXI deficiency) on protection from thrombosis. Patients and Methods: All patients with FXII or FXI deficiency and thrombosis were gathered from a time-unlimited PubMed search that was carried out twice and from personal records. Combined defects were excluded. The defect had to be proven by the demonstration of a suited hereditary pattern and by a specific clotting assay. Only patients with a factor activity level of <30% of normal were selected. Results: Twenty-eight patients with an FXII deficiency presented with arterial thrombosis, mainly myocardial infarction, and 29 showed venous thrombosis; for FXI deficiency, these figures were 43 and 10, respectively. The ratio of arterial and venous thrombosis was 0.96 and 4.3, respectively, for FXII and FXI deficiency. Conclusions: Factor FXII deficiency supplies no protection from arterial or venous thrombosis. FXI deficiency shows no protection from arterial thrombosis but appears to guarantee protection from venous thrombosis. A symptomatic, namely bleeding, condition (FXI deficiency) provides protection from venous thrombosis whereas an asymptomatic one (FXII deficiency) does not.
Benefit of Preoperative Oral Steroids during Sinus Surgery when Utilizing Concentrated Topical Epinephrine
Authors: Korkmaz Hakan , Yao William , Korkmaz Mukadder , Bleier Benjamin S.
Published: July 2016

Background/Aims: Oral steroids have been advocated in the preoperative setting as a means of reducing intraoperative blood loss and surgical time during sinus surgery. The purpose of this study was to analyze the impact of preoperative oral steroid administration on intraoperative bleeding and surgical duration when coupled with concentrated topical epinephrine. Methods: The medical records of 302 patients who underwent bilateral ‘full house' sinus surgery were reviewed. Concentrated topical epinephrine and inhalational anesthesia was used in all patients. Surgical duration and estimated blood loss were compared between the preoperative steroid-exposed and steroid-naive groups. χ2 and Student's t tests were used for statistical analysis. Results: One hundred and forty-two patients were exposed to steroid, while the remaining 160 were steroid naive. No significant differences were found with respect to surgical time between the steroid-exposed (96.91 ± 25.97 min) and steroid-naive patients (91.24 ± 32.29 min, p = 0.100). The steroid-exposed group demonstrated a marginally increased blood loss (66.03 ± 55.81 ml) as compared to steroid-naive patients (55.00 ± 38.71 ml, p = 0.048). Conclusion: When coupled with intraoperative concentrated topical epinephrine use, preoperative oral steroid administration provides no clinically significant benefit with respect to reduced intraoperative bleeding or surgical duration.
Empreendedorismo e gamificação no desenvolvimento profissional
Authors: Pinto Rosalice Botelho
Published: July 2016

Este artigo, centrado essencialmente na perspectiva teórica do Interacionismo Sociodiscursivo (BRONCKART, 1999, 2008), procura mostrar, a partir de algumas figuras competenciais (PINTO, 2015) identificadas empiricamente, a importância do uso dos serious games (jogos sérios) e da gamificação para o desenvolvimento dessas figuras. É a partir da configuração linguística das formas de interpretar do que venha a ser o empreendedorismo em função de referentes diversos que definiremos, primeiramente, as figuras competenciais empreendedoras. Defende-se, assim, a ideia de que existem grupos de configurações linguísticas específicas que podem vir a retratar diferentes formas de pensar e interpretar o agir empreendedor, variáveis de acordo com a diversidade referencial. Para análise foram realizadas transcrições de debates de ideias sobre a temática ação empreendedora junto a graduandos de 1º ano, integrados em universidades públicas e privadas portuguesas, em faculdades distintas. Resultados preliminares apontam, a partir do levantamento de algumas categorias linguísticas, que as figuras competenciais apresentam diferentes ´tonalidades´ em função da atividade social em que o agir empreendedor se veicula.
Optimal Levels of All Major Cardiovascular Risk Factors in Younger Age and Functional Disability in Older Age
Authors: Vu Thanh-Huyen T. , Lloyd-Jones Donald M. , Liu Kiang , Stamler Jeremiah , Garside Daniel B. , Daviglus Martha L.
Published: July 2016

Background—

The associations of optimal levels of all major cardiovascular disease risk factors, that is, low risk, in younger age with subsequent cardiovascular disease morbidity and mortality have been well documented. However, little is known about associations of low-risk profiles in younger age with functional disability in older age.

Methods and Results—

The sample included 6014 participants from the Chicago Heart Association Detection Project in Industry Study. Low-risk status, defined as untreated systolic/diastolic blood pressure ≤120/≤80 mm Hg, untreated serum total cholesterol <5.18 mmol/l, not smoking, body mass index < 25 kg/m
2
, and no diabetes mellitus, was assessed at baseline (1967 to 1973). Functional disability, categorized as (1) any disability in activities of daily living (ADLs), (2) any disability in instrumental ADLs but not in ADL, or (3) no disability, was assessed from the 2003 health survey. There were 39% women, 4% Black, with a mean age of 43 years and 6% low-risk status at baseline. After 32 years, 7% reported having limitations in performing any ADL and 11% in any instrumental ADL only. The prevalence of any ADL limitation was lowest in low-risk people and increased in a graded fashion with less-favorable risk factor groups (
P
trend <0.001). Compared with those with 2+ high-risk factors, the multivariable-adjusted odds of having any disability in ADLs versus no disability in people with low risk, any moderate risk, and 1 high-risk factor at baseline were lower by 58%, 48%, and 37%, respectively. Results were similar for instrumental ADLs, in both men and women.

Conclusions—

Having an optimal cardiovascular disease risk factor profile at younger age is associated with the lowest rate of functional disability in older age.
A Genetic Response Score for Hydrochlorothiazide Use
Authors: Shahin Mohamed H. , Gong Yan , McDonough Caitrin W. , Rotroff Daniel M. , Beitelshees Amber L , Garrett Timothy J. , Gums John G. , Motsinger-Reif Alison , Chapman Arlene B. , Turner Stephen T. , Boerwinkle Eric , Frye Reginald F. , Fiehn Oliver , Cooper-DeHoff Rhonda M. , Kaddurah-Daouk Rima , Johnson Julie A.
Published: July 2016

Hydrochlorothiazide is among the most commonly prescribed antihypertensives; yet, <50% of hydrochlorothiazide-treated patients achieve blood pressure (BP) control. Herein, we integrated metabolomic and genomic profiles of hydrochlorothiazide-treated patients to identify novel genetic markers associated with hydrochlorothiazide BP response. The primary analysis included 228 white hypertensives treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. Genome-wide analysis was conducted using Illumina Omni 1 mol/L-Quad Chip, and untargeted metabolomics was performed on baseline fasting plasma samples using a gas chromatography-time-of-flight mass spectrometry platform. We found 13 metabolites significantly associated with hydrochlorothiazide systolic BP (SBP) and diastolic BP (DBP) responses (false discovery rate, <0.05). In addition, integrating genomic and metabolomic data revealed 3 polymorphisms (rs2727563
PRKAG2
, rs12604940
DCC
, and rs13262930
EPHX2
) along with arachidonic acid, converging in the netrin signaling pathway (
P
=1×10
−5
), as potential markers, significantly influencing hydrochlorothiazide BP response. We successfully replicated the 3 genetic signals in 212 white hypertensives treated with hydrochlorothiazide and created a response score by summing their BP-lowering alleles. We found patients carrying 1 response allele had a significantly lower response than carriers of 6 alleles (∆SBP/∆DBP: −1.5/1.2 versus −16.3/−10.4 mm Hg, respectively, SBP score,
P
=1×10
−8
and DBP score,
P
=3×10
−9
). This score explained 11.3% and 11.9% of the variability in hydrochlorothiazide SBP and DBP responses, respectively, and was further validated in another independent study of 196 whites treated with hydrochlorothiazide (DBP score,
P
=0.03; SBP score,
P
=0.07). This study suggests that
PRKAG2
,
DCC
, and
EPHX2
might be important determinants of hydrochlorothiazide BP response.
Synoptic revision of the genus Cyrtorchis Schltr. (Angraecinae, Orchidaceae) in Central Africa, with the description of a new species restricted to submontane vegetation
Authors: AZANDI LAURA , STEVART TARIQ , SONKÉ BONAVENTURE , SIMO-DROISSART MURIELLE , AVANA MARIE-LOUISE , DROISSART VINCENT
Published: July 2016

As a preliminary step to the taxonomic revision of the genus Cyrtorchis, a synoptic revision of the species occurring in Central Africa was undertaken. Based on a detailed examination of 1,039 herbarium specimens, including nomenclatural types, we have recognized 14 species in Central Africa (one of which is divided into two subspecies), including one new species that the study brought to light, described here as Cyrtorchis submontana. The new species closely resembles C. guillaumetii and C. brownii in general aspect, but differs from them in having thinner, small elliptic leaves and shorter, fewer-flowered, more lax inflorescences with shorter bracts. The species is restricted to submontane vegetation of Central Africa and is assessed as Endangered following the IUCN Red List Categories and Criteria. Cyrtorchis latibracteata and C. subcylindrifolia are lectotypified, and the latter is placed as a synonym under C. henriquesiana. Many new records are reported, and for each taxon the distribution, habitat and ecology are given. An identification key for the Central African taxa is also provided.
A new species of Tinodes (Trichoptera: Psychomyiidae) from Madagascar
Authors: MELNITSKY STANISLAV I. , IVANOV VLADIMIR D.
Published: July 2016

The genus Tinodes (Psychomyiidae) has a wide distribution in the Eastern Hemisphere with the richest species assemblages in the Oriental and southern parts of the Western Palearctic regions. In comparison with the species assemblages in those regions, diversity of the African species of this genus is relatively poor. A brief review of the 10 then-known Afrotropical species belonging to the genus Tinodes was published by Johanson & Oláh (2007) together with descriptions of 14 new species. Some of these new species came from the Eastern African Arc of crystalline mountains, although 5 species have been found in Madagascar and the Comoros where no species of the genus Tinodes have been known previously. These new findings suggest continuing poor knowledge of the Afrotropical faunas where many species escaped descriptions until the beginning of the XXI century.
Morphology of the immature female stages and the wax test of ten species of Ceroplastes (Hemiptera: Coccomorpha: Coccidae: Ceroplastinae) from Brazil
Authors: ROSA KEILA C. C. , PERONTI ANA L. B. G. , HODGSON CHRIS J. , SOUSA-SILVA CARLOS R.
Published: July 2016

This paper describes the development of the waxy test and the microscopic characters of the three female nymphal instars of Ceroplastes cirripediformis Comstock, C. diospyros Hempel, C. floridensis Comstock, C. flosculoides Matile-Ferrero, C. formicarius Hempel, C. formosus Hempel, C. grandis Hempel, C. iheringi Cockerell, C. lucidus Hempel, and C. stellifer (Westwood). The discussion compares their morphology and divides the species into three groups according to the pattern of their dermal and wax characters.
The Yellow-green Bush-tanager is neither a bush-tanager nor a sparrow:
Molecular phylogenetics reveals that Chlorospingus flavovirens is a tanager (Aves: Passeriformes; Thraupidae)
Authors: AVENDAÑO JORGE ENRIQUE , BARKER F. KEITH , CADENA CARLOS DANIEL
Published: July 2016

Molecular phylogenetic analyses of the genus Chlorospingus (Aves: Emberizidae) indicate that the genus is not monophyletic because Chlorospingus flavovirens is actually a member of the tanager family (Thraupidae), in which its closest relatives are members of the genus Bangsia. We thus propose that C. flavovirens be transferred to Thraupidae and to the genus Bangsia.
Two new species and key to six species of the genus Taipodisma Yin, Zheng & Yin, 2014 from Taiwan, China (Orthoptera, Acridoidea, Catantopidae, Podisminae)
Authors: ZHENG FANG-QIANG , SHI JIAN-PING , DANG YAN
Published: July 2016

Two new species of the genus Taipodisma Yin et al, 2014 from Taiwan, China are described in this paper. The new species Taipodisma viriditibia sp. nov. is similar to Taipodisma hsiehi Yin et al., 2014, it differs from the latter by antennae longer, length of a middle segment 4.0 times its width; interspace of mesosternum longer in male, the length 2.0 times the narrowest; lateral lobes of metasternum slightly separated in male; epiproct of male with longitudinal sulcus at base only and length of subgenital plate of female longer than width. The new species Taipodisma kaohsiungensis sp. nov. is similar to Taipodisma nigritibia Yin et al., 2014, it differs from the latter by prozona of pronotum 1.2 times metazona; length of interspace as long as the narrowest in mesosternum of male; hind tibia yellowish green on lower side and length of subgenital plate longer than width in female. The type specimens are deposited in the National Museum of Natural Science, Taichung, Taiwan, China and the Institute of Entomology, Taiwan University, Taibei, Taiwan, China, respectively.