bluuebunny/crossref_metadata_2025 huggingface dataset:
TIM-1 Promotes Hepatitis C Virus Cell Attachment and Infection
Authors: Wang Jing , Qiao Luhua , Hou Zhouhua , Luo Guangxiang
Published: November 2016

Human TIM and TAM family proteins were recently found to serve as phosphatidylserine (PS) receptors which promote infections by many different viruses, including dengue virus, West Nile virus, Ebola virus, Marburg virus, and Zika virus. In the present study, we provide substantial evidence demonstrating that TIM-1 is important for efficient infection by hepatitis C virus (HCV). The knockdown of TIM-1 expression significantly reduced HCV infection but not HCV RNA replication. Likewise, TIM-1 knockout in Huh-7.5 cells remarkably lowered HCV cell attachment and subsequent HCV infection. More significantly, the impairment of HCV infection in the TIM-1 knockout cells could be restored completely by ectopic expression of TIM-1 but not TIM-3 or TIM-4. Additionally, HCV infection and cell attachment were inhibited by PS but not by phosphatidylcholine (PC), demonstrating that TIM-1-mediated enhancement of HCV infection is PS dependent. The exposure of PS on the HCV envelope was confirmed by immunoprecipitation of HCV particles with a PS-specific monoclonal antibody. Collectively, these findings demonstrate that TIM-1 promotes HCV infection by serving as an attachment receptor for binding to PS exposed on the HCV envelope.

IMPORTANCE
TIM family proteins were recently found to enhance infections by many different viruses, including several members of the
Flaviviridae
family. However, their importance in HCV infection has not previously been examined experimentally. The TIM family proteins include three members in humans: TIM-1, TIM-3, and TIM-4. The findings derived from our studies demonstrate that TIM-1, but not TIM-3 or TIM-4, promotes HCV infection by functioning as an HCV attachment factor. Knockout of the TIM-1 gene resulted in a remarkable reduction of HCV cell attachment and infection. PS-containing liposomes blocked HCV cell attachment and subsequent HCV infection. HCV particles could also be precipitated with a PS-specific monoclonal antibody. These findings suggest that TIM-1 and its binding ligand, PS, may serve as novel targets for antiviral intervention.
Structure of the Open Reading Frame 49 Protein Encoded by Kaposi's Sarcoma-Associated Herpesvirus
Authors: Hew Kelly , Veerappan Saranya , Sim Daniel , Cornvik Tobias , Nordlund Pär , Dahlroth Sue-Li
Published: November 2016

Herpesviruses alternate between the latent and the lytic life cycle. Switching into the lytic life cycle is important for herpesviral replication and disease pathogenesis. Activation of a transcription factor replication and transcription activator (RTA) has been demonstrated to govern this switch in Kaposi's sarcoma-associated herpesvirus (KSHV). The protein encoded by open reading frame 49 from KSHV (ORF49
KSHV
) has been shown to upregulate lytic replication in KSHV by enhancing the activities of the RTA. We have solved the crystal structure of the ORF49
KSHV
protein to a resolution of 2.4 Å. The ORF49
KSHV
protein has a novel fold consisting of 12 alpha-helices bundled into two pseudodomains. Most notably are distinct charged patches on the protein surface, which are possible protein-protein interaction sites. Homologs of the ORF49
KSHV
protein in the gammaherpesvirus subfamily have low sequence similarities. Conserved residues are mainly located in the hydrophobic regions, suggesting that they are more likely to play important structural roles than functional ones. Based on the identification and position of three sulfates binding to the positive areas, we performed some initial protein-DNA binding studies by analyzing the thermal stabilization of the protein in the presence of DNA. The ORF49
KSHV
protein is stabilized in a dose-responsive manner by double-stranded oligonucleotides, suggesting actual DNA interaction and binding. Biolayer interferometry studies also demonstrated that the ORF49
KSHV
protein binds these oligonucleotides.

IMPORTANCE
Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumorigenic gammaherpesvirus that causes multiple cancers and lymphoproliferative diseases. The virus exists mainly in the quiescent latent life cycle, but when it is reactivated into the lytic life cycle, new viruses are produced and disease symptoms usually manifest. Several KSHV proteins play important roles in this reactivation, but their exact roles are still largely unknown. In this study, we report the crystal structure of the open reading frame 49 protein encoded by KSHV (ORF49
KSHV
). Possible regions for protein interaction that could harbor functional importance were found on the surface of the ORF49
KSHV
protein. This led to the discovery of novel DNA binding properties of the ORF49
KSHV
protein. Evolutionary conserved structural elements with the functional homologs of ORF49
KSHV
were also established with the structure.
Impact of the introduction of rotavirus vaccination on paediatric hospital admissions, Lothian, Scotland: a retrospective observational study
Authors: Forrest Ruth , Jones Laura , Willocks Lorna , Hardie Alison , Templeton Kate
Published: November 2016

Objective

Rotavirus (RV) vaccination was introduced into the UK vaccination schedule in July 2013. This retrospective observational study assessed, in a UK setting, the impact of the vaccination programme on the number of RV gastroenteritis (RVGE) admissions, the complications of RVGE in hospitalised children, and the impact on hospital-acquired RVGE.

Design

Over a 3 year period, 1-year before and 2 years after the introduction of the vaccine, children under 13 years of age in Lothian region with RV+ve stool sample by PCR were identified, retrospectively, and admission data (length of stay, complications) and vaccination status analysed. Viral strain (vaccine/wild type) was typed using PCR-based methods in vaccinated children.

Results

Vaccination uptake in the first 2 years of the programme was 93–94%. In the 2 years following vaccine introduction, the annual number of confirmed RVGE admissions fell by 84.7% (95% CI 75.4 to 91.0), from 131 to 20, bed days reduced by 91.1% (86.9 to 94.1), from 325 to 29, and suspected hospital-acquired infections reduced by 95.7% (73.5–99.5), from 23 to 1. The reduction in admissions was seen across all age groups despite the vaccination only being administered to infants. Despite the reduction in incidence, complication rates in children admitted with RVGE remained unchanged across the three study years. A frequent incidental finding was RV vaccine strain in the stools of vaccinated children, up to 43 days after last immunisation. There has been no concurrent increase in rate of intussusception in the region.

Conclusions

These results provide encouraging initial evidence of the public health benefit, including to the unimmunised population, of the RV vaccination programme in the UK.
Dementia and Imagination: a mixed-methods protocol for arts and science research
Authors: Windle Gill , Newman Andrew , Burholt Vanessa , Woods Bob , O'Brien Dave , Baber Michael , Hounsome Barry , Parkinson Clive , Tischler Victoria
Published: November 2016

Introduction

Dementia and Imagination is a multidisciplinary research collaboration bringing together arts and science to address current evidence limitations around the benefits of visual art activities in dementia care. The research questions ask: Can art improve quality of life and well-being? If it does make a difference, how does it do this—and why? Does it have wider social and community benefits?

Methods and analysis

This mixed-methods study recruits participants from residential care homes, National Health Service (NHS) wards and communities in England and Wales. A visual art intervention is developed and delivered as 1×2-hour weekly group session for 3 months in care and community settings to N=100 people living with dementia. Quantitative and qualitative data are collected at 3 time points to examine the impact on their quality of life, and the perceptions of those who care for them (N=100 family and professional carers). Repeated-measures systematic observations of well-being are obtained during the intervention (intervention vs control condition). The health economics component conducts a social return on investment evaluation of the intervention. Qualitative data are collected at 3 time points (n=35 carers/staff and n=35 people living with dementia) to explore changes in social connectedness. Self-reported outcomes of the intervention delivery are obtained (n=100). Focus groups with intervention participants (n=40) explore perceptions of impact. Social network analysis of quantitative and qualitative data from arts and healthcare professionals (N=100) examines changes in perceptions and practice.

Ethics and dissemination

The study is approved by North Wales Research Ethics Committee—West. A range of activities will share the research findings, including international and national academic conferences, quarterly newsletters and the project website. Public engagement projects will target a broad range of stakeholders. Policy and practice summaries will be developed. The visual art intervention protocol will be developed as a freely available practitioners guide.
Therapy discontinuation or substitution in patients with cardiovascular disease, switching among different products of the same off-patent active substance: a ‘real-world’ retrospective cohort study
Authors: Degli Esposti Luca , Sangiorgi Diego , Buda Stefano , Degli Esposti Ezio , Scaglione Francesco
Published: November 2016

Objective

The present study investigated the effects of switching to different products of the same off-patent active substance (brand name or generic) on therapy discontinuation or substitution with another molecule of the same class, in patients with cardiovascular disease treated with statins and antihypertensives in a ‘real-world’ setting.

Design

A retrospective cohort study in a ‘real-world’ setting.

Setting

Analysis of data performed by integrating administrative databases that included approximately two million individuals who are assisted by the National Health System from three Local Health Units located in three different regions of Italy.

Participants

All patients aged ≥18 years with at least one prescription of simvastatin, ramipril or amlodipine in the period 1 January to 31 December 2010 were included and followed up for 2 years.

Main outcome measures

Prescription refills occurring during follow-up were evaluated. Frequency of discontinuation of therapy or substitution with another molecule of the same class (eg, from simvastatin to a different statin) during follow-up was identified.

Results

During follow-up, therapy discontinuation or substitution was found to be more frequent in patients switching to a different product of the same active substance compared with non-switching patients (11.5% vs 10.8% and 22.2% vs 20.8% (p=0.002), respectively, in the simvastatin group; 4.0% vs 3.5% and 24.6% vs 22.7% (p<0.001), respectively, in the amlodipine group). In the ramipril group, 8% of patients undertook a therapy substitution to another molecule; no trend towards a lower percentage of substitution was observed in the non-switching group, while 18% of patients discontinued treatment, with a significant difference in favour of patients not switching. These findings were partially confirmed by multivariate analysis.

Conclusions

Switches among products of the same active substance are quite common in patients with cardiovascular disease. Our study suggests that switching may expose patients to a higher risk of therapy discontinuation or substitution.
Protocol for the economic evaluation of a community-based intervention to improve growth among children under two in rural India (CARING trial)
Authors: Skordis-Worrall Jolene , Sinha Rajesh , Kumar Ojha Amit , Sarangi Soumendra , Nair Nirmala , Tripathy Prasanta , Sachdev H S , Bhattacharyya Sanghita , Gope Rajkumar , Rath Shibanand , Rath Suchitra , Srivastava Aradhana , Batura Neha , Pulkki-Brännström Anni-Maria , Costello Anthony , Copas Andrew , Saville Naomi , Prost Audrey , Haghparast-Bidgoli Hassan
Published: November 2016

Introduction

Undernutrition affects ∼165 million children globally and contributes up to 45% of all child deaths. India has the highest proportion of global undernutrition-related morbidity and mortality. This protocol describes the planned economic evaluation of a community-based intervention to improve growth in children under 2 years of age in two rural districts of eastern India. The intervention is being evaluated through a cluster-randomised controlled trial (cRCT, the CARING trial).

Methods and analysis

A cost-effectiveness and cost–utility analysis nested within a cRCT will be conducted from a societal perspective, measuring programme, provider, household and societal costs. Programme costs will be collected prospectively from project accounts using a standardised tool. These will be supplemented with time sheets and key informant interviews to inform the allocation of joint costs. Direct and indirect costs incurred by providers will be collected using key informant interviews and time use surveys. Direct and indirect household costs will be collected prospectively, using time use and consumption surveys. Incremental cost-effectiveness ratios (ICERs) will be calculated for the primary outcome measure, that is, cases of stunting prevented, and other outcomes such as cases of wasting prevented, cases of infant mortality averted, life years saved and disability-adjusted life years (DALYs) averted. Sensitivity analyses will be conducted to assess the robustness of results.

Ethics and dissemination

There is a shortage of robust evidence regarding the cost-effectiveness of strategies to improve early child growth. As this economic evaluation is nested within a large scale, cRCT, it will contribute to understanding the fiscal space for investment in early child growth, and the relative (in)efficiency of prioritising resources to this intervention over others to prevent stunting in this and other comparable contexts. The protocol has all necessary ethical approvals and the findings will be disseminated within academia and the wider policy sphere.

Trial registration number

ISRCTN51505201; pre-results.
‘I'll be in a safe place’: a qualitative study of the decisions taken by people with advanced cancer to seek emergency department care
Authors: Henson Lesley A , Higginson Irene J , Daveson Barbara A , Ellis-Smith Clare , Koffman Jonathan , Morgan Myfanwy , Gao Wei
Published: November 2016

Objective

To explore the decisions of people with advanced cancer and their caregivers to seek emergency department (ED) care, and understand the issues that influence the decision-making process.

Design

Cross-sectional qualitative study incorporating semistructured patient and caregiver interviews.

Methods

Between December 2014 and July 2015, semistructured interviews were conducted with 18 people with advanced cancer, all of whom had recently attended the ED of a large university teaching hospital located in south-east London; and six of their caregivers. Interviews were audio recorded, transcribed verbatim and analysed using a constant comparative approach. Padgett and Brodsky's modified version of the ‘Behavioral Model of Health Services Use’ was used as a framework to guide the study.

Results

Issues influencing the decision-making process included: (1) disease-related anxiety—those with greater anxiety related to their cancer diagnosis interpreted their symptoms as more severe and/or requiring immediate attention; (2) prior patterns of health-seeking behaviour—at times of crisis participants defaulted to previously used services; (3) feelings of safety and familiarity with the hospital setting—many felt reassured by the presence of healthcare professionals and monitoring of their condition; and, (4) difficulties accessing community healthcare services—especially urgently and/or out-of-hours.

Conclusions

These data provide healthcare professionals and policymakers with a greater understanding of how systems of care may be developed to help reduce ED visits by people with advanced cancer. In particular, our findings suggest that the number of ED visits could be reduced with greater end-of-life symptom support and education, earlier collaboration between oncology and palliative care, and with increased access to community healthcare services.
PRPS1 silencing reverses cisplatin resistance in human breast cancer cells
Authors: He Min , Chao Lin , You Yi-Ping
Published: November 2016

PRPS1 (phosphoribosyl pyrophosphate synthetase 1), which drives the nucleotide biosynthesis pathway, modulates a variety of functions by providing central building blocks and cofactors for cell homeostasis. As tumor cells often display abnormal nucleotide metabolism, dysregulated de-novo nucleotide synthesis has potential impacts in cancers. We now report that PRPS1 is specifically and highly expressed in chemoresistant (CR) cancer cells derived from cisplatin-resistant human breast cancer cell lines SK-BR-3 and MCF-7. The inhibition of PRPS1 activity in CR cells by genetic silencing reduces cell viability and increases apoptosis in vitro, both of which can be further potentiated by cisplatin treatment. Significantly, such down-regulation of PRPS1 in CR cells when administered to nude mice enhanced the survival of those animals, as demonstrated by decreased tumor growth. Knockdown of PRPSI may cause these effects by potently inducing autonomous activation of caspase-3 and inhibiting the proliferation in the engrafted CR tumors. As a result, cisplatin sensitivity in a xenograft model of CR cancer cells can be restored by the down-regulation of PRPS1. Thus, PRPS1 inhibition may afford a therapeutic approach to relapsed patients with breast cancer, resistant to chemotherapy.
Effect of speed limits at speed transition zones
Authors: Wang Xu , Bie Yuwei , Qiu Tony Z. , Niu Lei
Published: November 2016

Speed limits are a common traffic regulation for balancing traffic mobility and safety on roadways. Speed transition zones bear complicated driver behaviours. However, driver behaviours are even more complex when speed transition zones are dynamically created and shifted by variable speed limits (VSLs). Much existing research has estimated long-term driver compliance, evaluated effectiveness of speed enforcement, and attempted to involve compliance into VSL control algorithms. Whereas, limited research provides convincing solutions for representing speed limit effect and estimating real-time driver compliance at speed transition zones. To fill this research gap, this paper analyses field data from two speed transition zones along southbound of 97th Street, Edmonton, Canada. Temporal and spatial variations of speed and driver compliance are investigated in detail using statistical tests. A linear regression is then established to rank the contributions of the selected factors. Finally, some suggestions and guidelines for VSL algorithm design and implementation are proposed.
Piezoelectric interaction in controlling the effective electron temperature and the non-ohmic mobility characteristics in GaN and other III–V compounds at low lattice temperature
Authors: Das B. , Basu A. , Das J. , Bhattacharya D.P.
Published: November 2016

In a compound semiconductor that lacks inversion symmetry, the free electrons interact simultaneously with the piezoelectric and acoustic phonons. This combined interaction principally controls the electrical transport at low lattice temperatures. Again, at low temperatures, the electrons in some of the compounds may be significantly perturbed for comparatively low fields, say, even for a fraction of a Vcm−1 or so, which effectively seems to be high enough, and the material exhibits electrical nonlinearity. Such a perturbed ensemble then attains a field dependent effective electron temperature Te, which exceeds the lattice temperature TL. The relative importance of the piezoelectric interaction in controlling the field dependence of the effective electron temperature, and therefrom, the non-ohmic mobility characteristics have been analyzed here under the condition of low lattice temperature. The numerical results obtained for InSb, InAs, and GaN are studied in detail. When compared with the experiments, the results here seem to give the same qualitative picture with respect to the variation of the non-ohmic mobility with the electric field for the indium compounds. The results, being interesting, stimulate further work in the same field.
Collision strength and effective collision strength for Ba XLVIII
Authors: Mohan Man , Goyal Arun , Khatri Indu , Singh Shougaijm Somorendro , Singh A.K.
Published: November 2016

Collision strengths for the lowest 52 fine-structure levels of Ba XLVIII have been computed using Dirac atomic R-matrix code (DARC). Resonances in the threshold region have been completely resolved and the contributions of these resonances to allowed and forbidden transitions have been presented. Effective collision strengths have also been determined within a temperature range from the ground state. Collision strengths from ground state have also been computed with the relativistic distorted wave method, the flexible atomic code (FAC) was used for checking the accuracy of our results. The present work represents a new and significant work with improvement in the field. We believe that our presented data of collision and effective collision strengths may be useful in the future for benchmark calculations and for plasma diagnostics.
Seizure Control in a Computational Model Using a Reinforcement Learning Stimulation Paradigm
Authors: Nagaraj Vivek , Lamperski Andrew , Netoff Theoden I
Published: November 2016

Neuromodulation technologies such as vagus nerve stimulation and deep brain stimulation, have shown some efficacy in controlling seizures in medically intractable patients. However, inherent patient-to-patient variability of seizure disorders leads to a wide range of therapeutic efficacy. A patient specific approach to determining stimulation parameters may lead to increased therapeutic efficacy while minimizing stimulation energy and side effects. This paper presents a reinforcement learning algorithm that optimizes stimulation frequency for controlling seizures with minimum stimulation energy. We apply our method to a computational model called the epileptor. The epileptor model simulates inter-ictal and ictal local field potential data. In order to apply reinforcement learning to the Epileptor, we introduce a specialized reward function and state-space discretization. With the reward function and discretization fixed, we test the effectiveness of the temporal difference reinforcement learning algorithm (TD(0)). For periodic pulsatile stimulation, we derive a relation that describes, for any stimulation frequency, the minimal pulse amplitude required to suppress seizures. The TD(0) algorithm is able to identify parameters that control seizures quickly. Additionally, our results show that the TD(0) algorithm refines the stimulation frequency to minimize stimulation energy thereby converging to optimal parameters reliably. An advantage of the TD(0) algorithm is that it is adaptive so that the parameters necessary to control the seizures can change over time. We show that the algorithm can converge on the optimal solution in simulation with slow and fast inter-seizure intervals.
Multiple Classifiers-Based Feature Fusion for RGB-D Object Recognition
Authors: Wu Yan , Li Jiqian , Bai Jing
Published: November 2016

RGB-D-based object recognition has been enthusiastically investigated in the past few years. RGB and depth images provide useful and complementary information. Fusing RGB and depth features can significantly increase the accuracy of object recognition. However, previous works just simply take the depth image as the fourth channel of the RGB image and concatenate the RGB and depth features, ignoring the different power of RGB and depth information for different objects. In this paper, a new method which contains three different classifiers is proposed to fuse features extracted from RGB image and depth image for RGB-D-based object recognition. Firstly, a RGB classifier and a depth classifier are trained by cross-validation to get the accuracy difference between RGB and depth features for each object. Then a variant RGB-D classifier is trained with different initialization parameters for each class according to the accuracy difference. The variant RGB-D-classifier can result in a more robust classification performance. The proposed method is evaluated on two benchmark RGB-D datasets. Compared with previous methods, ours achieves comparable performance with the state-of-the-art method.
An Efficient Java-Based Solver for Abstract Argumentation Frameworks: jArgSemSAT
Authors: Cerutti Federico , Vallati Mauro , Giacomin Massimiliano
Published: November 2016

Dung’s argumentation frameworks are adopted in a variety of applications, from argument-mining, to intelligence analysis and legal reasoning. Despite this broad spectrum of already existing applications, the mostly adopted solver—in virtue of its simplicity—is far from being comparable to the current state-of-the-art solvers. On the other hand, most of the current state-of-the-art solvers are far too complicated to be deployed in real-world settings. In this paper we provide and extensive description of jArgSemSAT, a Java re-implementation of ArgSemSAT. ArgSemSAT represents the best single solver for argumentation semantics with the highest level of computational complexity. We show that jArgSemSAT can be easily integrated in existing argumentation systems (1) as an off-the-shelf, standalone, library; (2) as a Tweety compatible library; and (3) as a fast and robust web service freely available on the Web. Our large experimental analysis shows that despite being written in Java, jArgSemSAT would have scored in most of the cases among the three bests solvers for the two semantics with highest computational complexity “Stable and Preferred” in the last competition on computational models of argumentation.
Nil-clean quadratic elements
Authors: Šter Janez
Published: November 2016

We provide a strong condition holding for nil-clean quadratic elements in any ring. In particular, our result implies that every nil-clean involution in a ring is unipotent. As a consequence, we give a complete classification of weakly nil-clean rings introduced recently in [Breaz, Danchev and Zhou, Rings in which every element is either a sum or a difference of a nilpotent and an idempotent, J. Algebra Appl. 15 (2016) 1650148, doi: 10.1142/S0219498816501486].
Theoretical study of Zeno and anti-Zeno effects on photodissociation dynamics: A model approach
Authors: Nath Bikram , Mondal Chandan Kumar
Published: November 2016

Zeno and anti-Zeno effects in the evolution of the multi-photonic dissociation dynamics of the diatomic molecule HBr[Formula: see text] owing to repeated measurements demand if the system in the initial state have been studied. The effects have been calculated numerically for the case of vibrational population transfer and dissociation dynamics of HBr[Formula: see text] taking it as a model. We use time-dependent Fourier grid Hamiltonian (TDFGH) method as a mathematical tool in presence of intense radiation field as perturbation. The effects have been explored through a probable mechanism of population transfer from the ground vibrational state to the different upper vibrational states which ultimately go to the dissociation continuum. The results show significant differences in the mechanism of population transfer and the significant role of time interval of measurement ([Formula: see text] in Zeno and anti-Zeno effects. In case of survival probability of ground vibrational states, there is Zeno effect when the frequency of the laser to which the molecule is submitted is near the vibrational [Formula: see text] to [Formula: see text] resonance, while there is anti-Zeno effect if it is far from this resonance.
Yolk-Shell Fe3O4-Polyaniline Decorated Pd-Ni Nanoparticles with Enhanced Performance for Direct Formic Acid Fuel Cell
Authors: Hosseinian Akram , Hosseinzadeh-Khanmiri Rahim , Ghorbani-Kalhor Ebrahim , Abolhasani Jafar , Babazadeh Mirzaagha , Vessally Esmail
Published: November 2016

The yolk-shell Fe3O4-polyaniline for decoration of Pd-Ni nanoparticles (yolk-shell Fe3O4-PANI/Pd-Ni) were synthesized and used as a new electrocatalyst for oxidation of formic acid. The yolk-shell Fe3O4-PANI/Pd-Ni catalyst provided superior catalyst performance for formic acid oxidation in H2SO4 aqueous solution. These yolk-shell Fe3O4-PANI/Pd-Ni catalysts were found to be more resistant to deactivation in the oxidation of formic acid than yolk-shell Fe3O4-PANI/Pd and Pd/C and to consistently show better long-term performances. The enhanced catalytic performance may arise from the unique structure and surface properties of the yolk-shell Fe3O4-PANI and bi-functional effect, which process extraordinary promotional effect on Pd catalyst.
Functional loss of DHRS7C induces intracellular Ca2+ overload and myotube enlargement in C2C12 cells via calpain activation
Authors: Arai Shinobu , Ikeda Masataka , Ide Tomomi , Matsuo Yuka , Fujino Takeo , Hirano Katsuya , Sunagawa Kenji , Tsutsui Hiroyuki
Published: November 2016

Dehydrogenase/reductase member 7C (DHRS7C) is a newly identified NAD/NADH-dependent dehydrogenase that is expressed in cardiac and skeletal muscle and localized in the endoplasmic/sarcoplasmic reticulum (ER/SR). However, its functional role in muscle cells remains to be fully elucidated. Here, we investigated the role of DHRS7C by analyzing mouse C2C12 myoblasts deficient in DHRS7C (DHRS7C-KO cells), overexpressing wild-type DHRS7C (DHRS7C-WT cells), or expressing mutant DHRS7C [DHRS7C-Y191F or DHRS7C-K195Q cells, harboring point mutations in the NAD/NADH-dependent dehydrogenase catalytic core domain (YXXXK)]. DHRS7C expression was induced as C2C12 myoblasts differentiated into mature myotubes, whereas DHRS7C-KO myotubes exhibited enlarged cellular morphology after differentiation. Notably, both DHRS7C-Y191F and DHRS7C-K195Q cells also showed similar enlarged cellular morphology, suggesting that the NAD/NADH-dependent dehydrogenase catalytic core domain is pivotal for DHRS7C function. In DHRS7C-KO, DHRS7C-Y191F, and DHRS7C-K195Q cells, the resting level of cytosolic Ca2+ and total amount of Ca2+ storage in the ER/SR were significantly higher than those in control C2C12 and DHRS7C-WT cells after differentiation. Additionally, Ca2+ release from the ER/SR induced by thapsigargin and 4-chloro-m-cresol was augmented in these cells and calpain, a calcium-dependent protease, was significantly activated in DHRS7C-KO, DHRS7C-Y191F, and DHRS7C-K195Q myotubes, consistent with the higher resting level of cytosolic Ca2+ concentration and enlarged morphology after differentiation. Furthermore, treatment with a calpain inhibitor abolished the enlarged cellular morphology. Taken together, our findings suggested that DHRS7C maintains intracellular Ca2+ homeostasis involving the ER/SR and that functional loss of DHRS7C leads to Ca2+ overload in the cytosol and ER/SR, resulting in enlarged cellular morphology via calpain activation.
Weight gain in mice on a high caloric diet and chronically treated with omeprazole depends on sex and genetic background
Authors: Saqui-Salces Milena , Tsao Amy C. , Gillilland Merritt G. , Merchant Juanita L.
Published: November 2016

The impact of omeprazole (OM), a widely used over-the-counter proton pump inhibitor, on weight gain has not been extensively explored. We examined what factors, e.g., diet composition, microbiota, genetic strain, and sex, might affect weight gain in mice fed a high caloric diet while on OM. Inbred C57BL/6J strain, a 50:50 hybrid (B6SJLF1/J) strain, and mice on a highly mixed genetic background were fed four diets: standard chow (STD, 6% fat), STD with 200 ppm OM (STD + O), a high-energy chow (HiE, 11% fat), and HiE chow with OM (HiE + O) for 17 wk. Metabolic analysis, body composition, and fecal microbiota composition were analyzed in C57BL/6J mice. Oral glucose tolerance tests were performed using mice on the mixed background. After 8 wk, female and male C57BL/6J mice on the HiE diets ate less, whereas males on the HiE diets compared with the STD diets gained weight. All diet treatments reduced energy expenditure in females but in males only those on the HiE + O diet. Gut microbiota composition differed in the C57BL/6J females but not the males. Hybrid B6SJLF1/J mice showed similar weight gain on all test diets. In contrast, mixed strain male mice fed a HiE + O diet gained ∼40% more weight than females on the same diet. In addition to increased weight gain, mixed genetic mice on the HiE + O diet cleared glucose normally but secreted more insulin. We concluded that sex and genetic background define weight gain and metabolic responses of mice on high caloric diets and OM.
The mechanosensitive BKα/β1 channel localizes to cilia of principal cells in rabbit cortical collecting duct (CCD)
Authors: Carrisoza-Gaytán Rolando , Wang Lijun , Schreck Carlos , Kleyman Thomas R. , Wang Wen-Hui , Satlin Lisa M.
Published: November 2016

Within the CCD of the distal nephron of the rabbit, the BK (maxi K) channel mediates Ca2+- and/or stretch-dependent flow-induced K+secretion (FIKS) and contributes to K+adaptation in response to dietary K+loading. An unresolved question is whether BK channels in intercalated cells (ICs) and/or principal cells (PCs) in the CCD mediate these K+secretory processes. In support of a role for ICs in FIKS is the higher density of immunoreactive apical BKα (pore-forming subunit) and functional BK channel activity than detected in PCs, and an increase in IC BKα expression in response to a high-K+diet. PCs possess a single apical cilium which has been proposed to serve as a mechanosensor; direct manipulation of cilia leads to increases in cell Ca2+concentration, albeit of nonciliary origin. Immunoperfusion of isolated and fixed CCDs isolated from control K+-fed rabbits with channel subunit-specific antibodies revealed colocalization of immunodetectable BKα- and β1-subunits in cilia as well as on the apical membrane of cilia-expressing PCs. Ciliary BK channels were more easily detected in rabbits fed a low-K+vs. high-K+diet. Single-channel recordings of cilia revealed K+channels with conductance and kinetics typical of the BK channel. The observations that 1) FIKS was preserved but 2) the high-amplitude Ca2+peak elicited by flow was reduced in microperfused CCDs subject to pharmacological deciliation suggest that cilia BK channels do not contribute to K+secretion in this segment, but that cilia serve as modulators of cell signaling.
Estrogens and Androgens in Skeletal Physiology and Pathophysiology
Authors: Almeida Maria , Laurent Michaël R. , Dubois Vanessa , Claessens Frank , O'Brien Charles A. , Bouillon Roger , Vanderschueren Dirk , Manolagas Stavros C.
Published: November 2016

Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution.
On the Splitting of the Einstein Field Equations with respect to General (1+3) Threading of Spacetime
Authors: Bejancu Aurel , Farran Hani Reda
Published: November 2016

Based on general (1+3) threading of the spacetime (M,g), we obtain a new and simple splitting of both the Einstein field equations (EFE) and the conservation laws in (M,g). As an application, we obtain the splitting of EFE in an almost FLRW universe with energy-momentum tensor of a perfect fluid. In particular, we state the perturbation Friedmann equations in an almost FLRW universe.
Coronary Angiography Safety between Transradial and Transfemoral Access
Authors: Sinha Santosh Kumar , Mishra Vikas , Afdaali Nasar , Jha Mukesh Jitendra , Kumar Ashutosh , Asif Mohammad , Thakur Ramesh , Varma Chandra Mohan
Published: November 2016

Background and Aim. The aim of study was to evaluate safety, feasibility, and procedural variables of transradial approach compared with transfemoral approach in a standard population of patients undergoing coronary catheterization as one of the major criticisms of the transradial approach is that it takes longer overall procedure and fluoroscopy time, thereby causing more radiation exposure. Method. Between January 2015 and December 2015, a total of 1,997 patients in LPS Institute of Cardiology, GSVM Medical College, Kanpur, UP, India, undergoing coronary catheterization were randomly assigned to the transradial or transfemoral approach. Result. Successful catheterization was achieved in 1045 of 1076 patients (97.1%) in the transradial group and in 918 of 921 patients (99.7%) in the transfemoral group (p=0.001). Comparing the transradial and transfemoral approaches, fluoroscopy time (2.46±1.22 versus 2.83±1.31 min; p=0.32), procedure time (8.89±2.72 versus 9.33±2.82 min; p=0.56), contrast volume (67.52±22.54 versus 71.63±25.41 mL; p=0.32), radiation dose as dose area product (24.2±4.21 versus 22.3±3.46 Gycm2; p=0.43), and postprocedural rise of serum creatinine (6±4.5% versus 8±2.6%; p=0.41) were not significantly different while vascular access site complications were significantly lower in transradial group than transfemoral group (3.9% versus 7.6%; p=0.04). Conclusion. The present study shows that transradial access for coronary angiography is safe among patients compared to transfemoral access with lower rate of local vascular complications.
The Nonmydriatic Fundus Camera in Diabetic Retinopathy Screening: A Cost-Effective Study with Evaluation for Future Large-Scale Application
Authors: Scarpa Giuseppe , Urban Francesca , Vujosevic Stela , Tessarin Michele , Gallo Giovanni , Visentin Annalisa , Foglia Emanuela , Ferrario Lucrezia , Midena Edoardo
Published: November 2016

Aims. The study aimed to present the experience of a screening programme for early detection of diabetic retinopathy (DR) using a nonmydriatic fundus camera, evaluating the feasibility in terms of validity, resources absorption, and future advantages of a potential application, in an Italian local health authority. Methods. Diabetic patients living in the town of Ponzano, Veneto Region (Northern Italy), were invited to be enrolled in the screening programme. The “no prevention strategy” with the inclusion of the estimation of blindness related costs was compared with screening costs in order to evaluate a future extensive and feasible implementation of the procedure, through a budget impact approach. Results. Out of 498 diabetic patients eligible, 80% was enrolled in the screening programme. 115 patients (34%) were referred to an ophthalmologist and 9 cases required prompt treatment for either proliferative DR or macular edema. Based on the pilot data, it emerged that an extensive use of the investigated screening programme, within the Greater Treviso area, could prevent 6 cases of blindness every year, resulting in a saving of €271,543.32 (−13.71%). Conclusions. Fundus images obtained with a nonmydriatic fundus camera could be considered an effective, cost-sparing, and feasible screening tool for the early detection of DR, preventing blindness as a result of diabetes.
A General Proximal Alternating Minimization Method with Application to Nonconvex Nonsmooth 1D Total Variation Denoising
Authors: Zhang Xiaoya , Sun Tao , Cheng Lizhi
Published: November 2016

We deal with a class of problems whose objective functions are compositions of nonconvex nonsmooth functions, which has a wide range of applications in signal/image processing. We introduce a new auxiliary variable, and an efficient general proximal alternating minimization algorithm is proposed. This method solves a class of nonconvex nonsmooth problems through alternating minimization. We give a brilliant systematic analysis to guarantee the convergence of the algorithm. Simulation results and the comparison with two other existing algorithms for 1D total variation denoising validate the efficiency of the proposed approach. The algorithm does contribute to the analysis and applications of a wide class of nonconvex nonsmooth problems.
Acute Kidney Injury in Hematopoietic Stem Cell Transplantation: A Review
Authors: Krishnappa Vinod , Gupta Mohit , Manu Gurusidda , Kwatra Shivani , Owusu Osei-Tutu , Raina Rupesh
Published: November 2016

Hematopoietic stem cell transplantation (HSCT) is a highly effective treatment strategy for lymphoproliferative disorders and bone marrow failure states including aplastic anemia and thalassemia. However, its use has been limited by the increased treatment related complications, including acute kidney injury (AKI) with an incidence ranging from 20% to 73%. AKI after HSCT has been associated with an increased risk of mortality. The incidence of AKI reported in recipients of myeloablative allogeneic transplant is considerably higher in comparison to other subclasses mainly due to use of cyclosporine and development of graft-versus-host disease (GVHD) in allogeneic groups. Acute GVHD is by itself a major independent risk factor for the development of AKI in HSCT recipients. The other major risk factors are sepsis, nephrotoxic medications (amphotericin B, acyclovir, aminoglycosides, and cyclosporine), hepatic sinusoidal obstruction syndrome (SOS), thrombotic microangiopathy (TMA), marrow infusion toxicity, and tumor lysis syndrome. The mainstay of management of AKI in these patients is avoidance of risk factors contributing to AKI, including use of reduced intensity-conditioning regimen, close monitoring of nephrotoxic medications, and use of alternative antifungals for prophylaxis against infection. Also, early identification and effective management of sepsis, tumor lysis syndrome, marrow infusion toxicity, and hepatic SOS help in reducing the incidence of AKI in HSCT recipients.
Physical‐Performance Outcomes and Biomechanical Correlates from the 32‐Week Yoga Empowers Seniors Study
Authors: Wang Man-Ying , Greendale Gail A. , Yu Sean S.-Y. , Salem George J.
Published: November 2016

Background. Yoga Empowers Seniors Study (YESS) quantified physical demands associated with yoga performance using biomechanical methods. This study evaluated the efficacy of the program on physical function outcomes. Methods. Twenty community‐dwelling older adults aged 70.7 ± 3.8 years attended biweekly 60‐minute Hatha yoga classes for 32 weeks. Four domains of the physical measurements including (1) functional performance, (2) flexibility, (3) muscle strength, and (4) balance were taken at the baseline, 16‐week and 32‐week time points. Repeated‐measures ANOVA omnibus tests and Tukey’s post hoc tests were employed to examine the differences in each outcome variable across the 3 time points. Results. Improved timed chair stands (p < 0.01), 8‐foot up and go (p < 0.05), 2‐min step test (p < 0.05), and vertical reach (p = 0.05) performance were evident. Isometric knee flexor strength (p < 0.05) and repetitions of the heel rise test (p < 0.001) also increased following the 32‐week intervention. Both flexibility and balance performance remained unchanged. Conclusions. Significant improvements in physical function and muscle‐specific lower‐extremity strength occur with the regular practice of a modified Hatha yoga program designed for seniors. These adaptations corresponded with the previously reported biomechanical demands of the poses.
Formulation of Propolis Phenolic Acids Containing Microemulsions and Their Biopharmaceutical Characterization
Authors: Žilius Modestas , Ramanauskienė Kristina , Juškaitė Vaida , Briedis Vitalis
Published: November 2016

Microemulsions (MEs) were formulated using PEG‐8 caprylic/capric glycerides and ethanolic propolis extracts. Characterization of MEs was performed by determining mean droplet size, polydispersity index, stability under varying external factors, and formulation effect on delivery of phenolic compounds into the skin ex vivo. Essential oils were included into the formulations of MEs and their influence on physical characteristics of the nanostructured systems as well as penetration into epidermis and dermis were evaluated. The droplet size, their distribution, and stability of the formulated MEs were not affected. Presence of essential oils in the formulation increased penetration of phenolic compounds in general, but only the amount of ferulic acid increased significantly. Mean droplet size increased with increase of oily phase amount, suggesting that phenolic compounds and components of essential oils were not modifying the formation of the interphase film composition and/or structure. Phenolic compounds were predominantly located in the lipid phase of the MEs thus minimizing their availability at the surface of the skin.
Statistical Uncertainty in Hydrometeorological Trend Analyses
Authors: Onyutha Charles
Published: November 2016

This study demonstrates the existence of uncertainty in hydrometeorological trend analyses using historical rainfall from Kenya in East Africa. With respect to the influence of short- and long-term persistence on trend analyses, a total of 13 approaches of rank-based techniques including Mann-Kendall, Spearman’s Rho, and Cumulative Rank Difference (CRD) tests were employed. Graphically, CRD-based diagnoses of trends and subtrends were performed. To assess data-related uncertainty, a resampling procedure was applied. It was shown that at a selected significance level, the null hypothesisH0(no trend) can be rejected for trend direction while the evidence to rejectH0(zero trend magnitude) is statistically insufficient. Graphical and statistical approaches when combined yield more influential and comprehensive information for inference than relying purely on statistical results. Alongside an apparent linear trend, variations in the nonlinear (e.g., cyclical) component of the series may also not be due to natural randomness. Method-related uncertainty is not negligible especially for series with persistent fluctuations. These findings shed light on the need to assess uncertainty on trend results. Furthermore, it is recommended that the conclusiveness of trends be cautiously premised not only on statistical grounds but also on more considered physical and/or theoretical understanding of the hydrometeorological processes.