bluuebunny/crossref_metadata_2025_split huggingface dataset:
On Neural Code – The Self-Information Processor disguised as neuronal variability?
Authors: Tsien Joe Z. , Li Meng 
Published: April 2017

AbstractOne important goal of BRAIN projects is to crack the neural code — to understand how information is represented in patterns of electrical activity generated by ensembles of neurons. Yet the major stumbling block in the understanding of neural code isneuronal variability- neurons in the brain discharge their spikes with tremendous variability in both thecontrolresting states and across trials within the same experiments. Such on-going spike variability imposes a great conceptual challenge to the classic rate code and/or synchrony-based temporal code. In practice, spike variability is typically removed via over-the-trial averaging methods such as peri-event spike histogram. In contrast to view neuronal variability as a noise problem, here we hypothesize that neuronal variability should be viewed as theself-information processor. Under this conceptual framework, neurons transmit their information by conforming to the basic logic of the statistical Self-Information Theory: spikes with higher-probability inter-spike-intervals (ISI) contain less information, whereas spikes with lower-probability ISIs convey more information, termed assurprisal spikes. In other words, real-time information is encoded not by changes in firing frequency per se, but rather by spike’s variability probability. When these surprisal spikes occur as positive surprisals or negative surprisals in a temporally coordinated manner across populations of cells, they generate cell-assembly neural code to convey discrete quanta of information in real-time. Importantly, such surprisal code can afford not only robust resilience to interference, but also biochemical coupling to energy metabolism, protein synthesis and gene expression at both synaptic sites and cell soma. We describe how this neural self-information theory might be used as a general decoding strategy to uncover the brain’s various cell assemblies in an unbiased manner.
Intragenomic Redistribution of Host Transcription Factor Binding WithToxoplasma GondiiInfection
Authors: Ulahannan Netha , Suzuki Masako , Simões-Pires Claudia A. , Wicik Zofia , Ari Wijetunga N. , Croken Matthew McKnight , Bhattacharyya Sanchari , Johnston Andrew D. , Kong Yu , Maqbool Shahina B. , Verma Amit , Greally John M. 
Published: April 2017

ABSTRACTThe intracellular pathogenToxoplasma gondiimodifies a number of host cell processes. The mechanisms by whichT. gondiialters host gene expression are incompletely understood. This study focuses on how the regulators of gene expression in human host cells respond toT. gondii24 hours following infection to cause specific patterns of transcriptional dysregulation. The most striking finding was the altered landscape of transposase-accessible chromatin by infection. We found both gains and losses of loci of open chromatin enriched in proximity to transcriptionally altered genes. Both DNA sequence motif analysis at the loci changing chromatin accessibility and network analysis of the genes with transcription and regulatory changes implicate a central role for the AP-1 transcription factor. We validated the redistribution of AP-1 in the host genome using chromatin immunoprecipitation studies of the c-Fos component of AP-1. As infection withT. gondiiis associated with the cell failing to progress through the cell cycle, all of the changes observed occur in the absence of cell division and within 24 hours, an insight into the dynamism of these transcriptional regulatory events. We conclude thatT. gondiiinfection influences transcriptional regulation through transcription factor re-targeting to modify thecis-regulatory landscape of the host nucleus.AUTHOR SUMMARYThe complex interactions between the intracellular pathogenToxoplasma gondiiand the host cell manifest as expression changes of host genes.T. gondii’ssecreted effectors have been extensively studied and include factors that influence the properties of transcription factors, resulting in post-translational modifications and changes in intracellular localization. To gain insights into howT. gondiiexerts specific influences on host transcriptional regulation, we used genome-wide approaches to study gene expression, cytosine modifications, and chromatin structure of the host cell 24 hours after infection. The greatest insights were gained from the mapping of loci of transposase-accessible chromatin, revealing a consistently altered pattern of a subset of loci becoming inaccessible, with the simultaneous acquisition of a new set of infection-associated loci of open chromatin. The sequences at these loci were enriched for certain transcription factor binding motifs, in particular that of AP-1, the transcription factor formed by c-Jun and c-Fos heterodimers. Network analysis revealed a central role for c-Jun and c-Fos in the infection-associated perturbations, prompting a chromatin immunoprecipitation approach that confirmed the redistribution of c-Fos in infected cells. We conclude that aT. gondiiinfection leads to an intragenomic redistribution of host transcription factor binding, with resulting effects on host gene expression.
Modeling of biomechanics and biorheology of red blood cells in type-2 diabetes mellitus
Authors: Chang Hung-Yu , Li Xuejin , Karniadakis George Em 
Published: April 2017

AbstractErythrocytes in patients with type-2 diabetes mellitus (T2DM) are associated with reduced cell deformability and elevated blood viscosity, which contribute to impaired blood flow and other pathophysiological aspects of diabetes related vascular complications. In this study, by using atwo-componentred blood cell (RBC) model and systematic parameter variation, we perform detailed computational simulations to probe the alteration of the biomechanical, rheological and dynamic behavior of T2DM RBCs in response to morphological change and membrane stiffening. First, we examine the elastic response of T2DM RBCs subject to static tensile forcing and their viscoelastic relaxation response upon release of the stretching force. Second, we investigate the membrane fluctuations of T2DM RBCs and explore the effect of cell shape on the fluctuation amplitudes. Third, we subject the T2DM RBCs to shear flow and probe the effects of cell shape and effective membrane viscosity on their tank-treading movement. In addition, we model the cell dynamic behavior in a microfluidic channel with constriction and quantify the biorheological properties of individual T2DM RBCs. Finally, we simulate T2DM RBC suspensions under shear and compare the predicted viscosity with experimental measurements. Taken together these simulation results and their comparison with currently available experimental data are helpful in identifying a specific parametric model the first of its kind that best describes the main hallmarks of T2DM RBCs, which can be used in future simulation studies of hematologic complications of T2DM patients.
Mitotic gene conversion tracts associated with repair of a defined double-strand break inSaccharomyces cerevisiae
Authors: Hum Yee Fang , Jinks-Robertson Sue 
Published: April 2017

AbstractMitotic recombination between homologous chromosomes can lead to loss-of-heterozygosity (LOH), which is an important contributor to human disease. In the current study, a defined double-strand break (DSB) on chromosome IV was used to initiate LOH in a yeast strain with sequence-diverged chromosomes. Associated gene conversion tracts, which reflect the repair of mismatches formed when diverged chromosomes exchange single strands, were mapped using microarrays. LOH events reflected two broken chromosomes, one of which was repaired as a crossover and the other as a noncrossover. Gene conversion tracts associated with individual crossover and noncrossover events were similar in size and position, with half of the tracts unexpectedly mapping to only a single side of the initiating break. Although the molecular features of DSB-initiated events generally agree with those predicted by current models of homologous recombination, there were unexpected complexities in associated gene conversion tracts.
Cross talk between photo-pigments and graphene electron cloud - Designing a biodiode
Authors: Ray Sanhita , Sen Sayantani , Das Alakananda , Bose Anirban , Bhattacharyya Anirban , Das Avishek , Chattopadhyay Sanatan , Patra Hirak , Singha Shib Shankar , Singha Achintya , Dasgupta Anjan Kr 
Published: April 2017

AbstractWe report emergence of a new electrical material by growing photosynthetic biofilm on a Dirac material, graphene. The material showed new conducting as well as semiconducting properties. Frequency dependent capacitive spectra further indicated presence of electrical isosbestic points(at 0.8 and 9MHz), implying two state dieletric transitions at critical frequencies. A notable reult was a Schottky diode like behavior in the IV curve. Voltage dependent conductance with conductance peaks near the Schottky diode threshold was observed. We obtained facilitated growth of photosynthetic biofilm in presence of graphene. Lastly higher bacterial metabolism i was seen in the biofilm in contact with graphene as compared to its normal growth condition. For this zero band gap Dirac material this can only be interpreted as coupling of the electron transport chain of the bacterial biofilm and the graphene electron cloud.
Global analysis of plasma lipids identifies liver-derived acyl-carnitines as a fuel source for brown fat thermogenesis
Authors: Simcox Judith , Geoghegan Gisela , Maschek John Alan , Mixon Amanda , Pasquali Marzia , Miao Ren , Lee Sanghoon , Jiang Lei , Huck Ian , Donato Anthony J. , Apte Udayan , Longo Nicola , Rutter Jared , Cox James , Villanueva Claudio J. 
Published: April 2017

SummaryCold induced thermogenesis is an energy demanding process that protects endotherms against a reduction in ambient temperature. Using non-targeted LC-MS based lipidomics, we identified plasma acylcarnitines as the most significantly changed lipid class in response to the cold. Here we show that acylcarnitines provide fuel for brown fat thermogenesis. In response to the cold, FFAs released from adipocytes activate the nuclear receptor HNF4α to stimulate the expression of genes involved in acylcarnitine metabolism in the liver. Conditional deletion of HNF4α in hepatocytes blocks the cold-induced changes in hepatic gene expression, lowering circulating long chain acylcarnitine (LCAC) levels, and impairing their ability to adapt to the cold. Finally, a bolus of L-carnitine or palmitoylcarnitine rescues the cold sensitivity seen with aging. Our data highlights an elegant mechanism whereby white adipose tissue provides FFAs for hepatic carnitilation to generate plasma LCAC as a fuel source for BAT thermogenesis.HighlightsBlood acylcarnitine levels increase in response to the cold.FFA mobilization in response to the cold activates hepatic HNF4α and stimulates genes involved in acylcarnitine metabolism.Brown adipocytes metabolize palmitoylcarnitine.Carnitine administration improves thermogenic response in aged mice.ETOCSimcox et al identified acylcarnitines as a novel source of energy for thermogenesis. In response to the cold, the liver activates a transcriptional program through the transcription factor HNF4α, leading to increased acylcarnitine levels. They also find that aging mice have reduced acylcarnitine levels and an impaired thermogenic response in the cold. Increasing acylcarnitine levels in old mice increases their ability to adapt to the cold. Their studies discover a physiological role for acylcarnitines in thermogenesis.Graphical AbstractCold exposure stimulates the sympathetic nervous system to release noradrenaline (NA). Activation of β3-adrenergic receptors stimulates FFA release and activation of the transcription factor HNF4α in the liver. This leads to increased gene expression of enzymes involved in acylcarnitine metabolism. The acylcarnitines are released in the blood to provide fuel for brown fat thermogenesis. These studies highlight the role of the liver in the thermogenic response.
Quantitative identification of senescent cells in aging and disease
Authors: Biran Anat , Zada Lior , Abou Karam Paula , Vadai Ezra , Roitman Lior , Ovadya Yossi , Porat Ziv , Krizhanovsky Valery 
Published: April 2017

SummarySenescent cells are present in premalignant lesions and sites of tissue damage and accumulate in tissues with age. In vivo identification, quantification and characterization of senescent cells are challenging tasks that limit our understanding of the role of senescent cells in diseases and aging. Here, we present a new way to precisely quantify and identify senescent cells in tissues on a single‐cell basis. The method combines a senescence‐associated beta‐galactosidase assay with staining of molecular markers for cellular senescence and of cellular identity. By utilizing technology that combines flow cytometry with high‐content image analysis, we were able to quantify senescent cells in tumors, fibrotic tissues, and tissues of aged mice. Our approach also yielded the finding that senescent cells in tissues of aged mice are larger than nonsenescent cells. Thus, this method provides a basis for quantitative assessment of senescent cells and it offers proof of principle for combination of different markers of senescence. It paves the way for screening of senescent cells for identification of new senescence biomarkers, genes that bypass senescence or senolytic compounds that eliminate senescent cells, thus enabling a deeper understanding of the senescent state in vivo.
Microfinance Interest Rate Puzzle: Price Rationing or Panic Pricing?
Authors: Guo Lin , Jo Hoje 
Published: April 2017

AbstractWe examine the relation between microfinance institution (MFI) interest rates, loan loss rates, and regulations. Our results suggest that a positive and causal association exists where loan loss rates drive MFI interest rates after controlling for confounding factors. This positive association holds after accounting for potential endogeneity based on various econometric methods and quasi‐natural experiment. Although endogeneity cannot be ruled out fully, the results of our tests suggest it plays a limited role. Our results support the price‐rationing proposition that MFIs ration credit and there is unmet demand at the market‐clearing price. This positive relation is more pronounced in countries with individualistic and uncertainty avoiding cultures.
Effect of Place of Incorporation, Chinese Culture, and Business Practices on Corporate Fraud: Evidence from Hong Kong Listed Companies
Authors: Pang Josephine Chui‐ling , Lo Simon Ming‐sum 
Published: April 2017

AbstractMainland Chinese companies make up more than 50% of the Hong Kong securities market in terms of number of listings and market capitalization. Our empirical results indicate that Chinese companies have a higher incidence of corporate fraud and greater fraud severity than other listed counterparts, even after controlling for state versus private ownership, internal corporate governance, financial standing, firm characteristics, and time factors. Further investigation reveals that incorporation in China and Chinese culture and business practices are two distinct and major driving factors in corporate fraud. Conventional explanatory variables for corporate fraud other than board tenure, firm size, listing year, and year of fraud detection do not have explanatory power in the Hong Kong context.
Estimating the Effect of Corporate Social Responsibility on Firm Value Using Geographic Identification
Authors: Chintrakarn Pandej , Jiraporn Pornsit , Jiraporn Napatsorn , Davidson Travis 
Published: April 2017

AbstractWe argue that firms located close to one another tend to have similar corporate social responsibility (CSR) policies, due to investor clienteles, local competition, as well as social interactions. Our results are consistent with this notion. In particular, firms located in the same 3‐digit zip code exhibit a similar degree of CSR. Exploiting the variation in CSR across zip codes, we estimate the effect of CSR on firm value. Part of the firm's CSR is induced by the surrounding firms in the same zip code and can be considered exogenous as it is determined outside the firm. Because zip code allocation is based on efficiency in mail delivery, and not on corporate policies or outcomes, it is likely exogenous. Our instrumental variable analysis reveals that more socially responsible firms enjoy significantly higher firm value. We confirm the results using phone number area codes, instead of zip codes, and reach the same conclusion.
Corporate Social Responsibility, Religion, and Firm Risk
Authors: Cui Jinhua , Jo Hoje , Na Haejung 
Published: April 2017

AbstractIn this article, we examine the empirical influence of the combined effect of Corporate social responsibility (CSR) and the degree of local community religiosity on firm risk by investigating their unidirectional and endogenous effects. Employing a large US sample, we find an inverse association between CSR–religiosity and firm risk after controlling for various firm characteristics. Also, after mitigating endogeneity bias, we still find a negative association between CSR–local community religiosity and firm risk. We interpret these results to support the social license to operate (SLO) explanation: the lower the level of firm risk, the higher the level of SLO.
Improvement in baroreflex control of renal sympathetic nerve activity in obese Sprague Dawley rats following immunosuppression
Authors: Khan S. A. , Sattar M. Z. A. , Abdullah N. A. , Rathore H. A. , Ahmad A. , Abdulla M. H. , Johns E. J. 
Published: April 2017

AbstractAimThis investigation explored the hypothesis that in obesity an inflammatory response in the kidney contributed to a renal nerve‐dependent blunting of the baroreflex regulation of renal sympathetic nerve activity.MethodsRats received a normal (12% kcal) or high‐fat (45% kcal) diet for 8 weeks plus daily injections of vehicle (0.9% NaCl i.p) or tacrolimus (0.25 mg kg−1 day−1 i.p) from weeks 3–8. Following anaesthesia, left renal sympathetic nerve activity was recorded, baroreflex gain curves were generated, by infusing phenylephrine and sodium nitroprusside, and cardiopulmonary baroreceptors challenged by infusing a saline load.ResultsThe high‐fat diet elevated weight gain and adiposity index by 89 and 129% (both, P < 0.001). Mean blood pressure (132 ± 4 vs 103 ± 5 mmHg), fractional noradrenaline excretion and creatinine clearance (5.64 ± 0.55 vs 3.32 ± 0.35 mL min−1 kg−1) were 28, 77 and 69% higher (all P < 0.05), but urine flow and fractional sodium excretions were 42 and 72% (both P < 0.001) lower compared to normal rats. Plasma and renal TNF‐α and IL‐6 concentrations were fourfold to fivefold (P < 0.001) and 22 and 20% higher (both, P < 0.05), in obese rats but normalized following tacrolimus. In obese rats, baroreflex sensitivity was reduced by 80% (P < 0.05) but restored by renal denervation or tacrolimus. Volume expansion reduced renal sympathetic nerve activity by 54% (P < 0.001) in normal and obese rats subjected to renal denervation and tacrolimus, but not in obese rats with an intact renal innervation.ConclusionObesity induced a renal inflammation and pointed to this being both the origin of autonomic dysregulation and a potential focus for targeted therapy.
Differential characteristics and prognosis of patients with hepatitis B virus‐related acute‐on‐chronic liver failure defined by European Association for the Study of the Liver – Chronic Liver Failure criteria
Authors: Wu Juan , Li Yuan‐Yuan , Hu Jin‐Hua , Jia Lin , Shi Ming , Meng Fan‐Ping , Li Juan , Zhao Juan , Wang Fu‐Sheng , Meng Qing‐Hua 
Published: April 2017

AimTo determine the differential characteristics and prognosis of patients with hepatitis B virus (HBV)‐related acute‐on‐chronic liver failure (ACLF) detected using Asian Pacific Association for the Study of the Liver (APASL) criteria and then classified using European Association for the Study of the Liver–Chronic Liver Failure (EASL‐CLIF) criteria.MethodsWe retrospectively reviewed 316 HBV‐related APASL ACLF patients treated at Beijing 302 Hospital or Beijing You'An Hospital (both Beijing, China) between February 2015 and February 2016. Clinical characteristics and mortality rates were compared among patients with different EASL‐CLIF ACLF severity grades (no ACLF, and ACLF grades 1–3).ResultsAccording to the EASL‐CLIF criteria, 138 patients had no ACLF, 123 had ACLF at enrollment, and 55 developed ACLF during hospitalization. Both 28‐day and 90‐day transplant‐free mortality were dramatically lower in patients without EASL‐CLIF ACLF (0.7% and 5.1%, respectively) than in patients with EASL‐CLIF ACLF (40.7% and 63.2%, respectively; both P < 0.001). Liver failure rates were similar in patients with and without EASL‐CLIF ACLF, but extrahepatic organ failure was rare in patients without EASL‐CLIF ACLF. Baseline serum creatinine, new bacterial infection and new acute kidney injury during hospitalization, maximum rising rates of CLIF‐C ACLF score, and Model for End‐stage Liver Disease score were independent predictors of EASL‐CLIF ACLF after enrollment.ConclusionsThe EASL‐CLIF ACLF classification can accurately prognosticate the short‐term mortality of patients with HBV‐related APASL ACLF. It can also distinguish distinct clinical characteristics and prognoses in patients with and without EASL‐CLIF ACLF.
Exploring the optimal sequence of abiraterone and enzalutamide in patients with chemotherapy‐naïve castration‐resistant prostate cancer: The Kyoto‐Baltimore collaboration
Authors: Terada Naoki , Maughan Benjamin L , Akamatsu Shusuke , Kobayashi Takashi , Yamasaki Toshinari , Inoue Takahiro , Kamba Tomomi , Ogawa Osamu , Antonarakis Emmanuel S 
Published: April 2017

ObjectivesTo evaluate and compare the efficacy of sequential treatment with abiraterone followed by enzalutamide or vice versa for castration‐resistant prostate cancer.MethodsWe retrospectively evaluated data on 198 consecutive chemotherapy‐naïve patients who had received both abiraterone and enzalutamide for castration‐resistant prostate cancer at Kyoto University Hospital (including satellite hospitals) and at Johns Hopkins Cancer Center. Prostate‐specific antigen progression‐free survival and overall survival in patients treated with sequential abiraterone‐to‐enzalutamide versus enzalutamide‐to‐abiraterone without intervening therapies were compared.ResultsOverall, 113 patients were treated with the abiraterone‐to‐enzalutamide sequence and 85 with the enzalutamide‐to‐abiraterone sequence. Median prostate‐specific antigen progression‐free survival was not significantly different between abiraterone and enzalutamide in the first‐line setting (hazard ratio 0.88, 95% confidence interval 0.66–1.19, P = 0.412), but there was an advantage favoring enzalutamide compared with abiraterone in the second‐line setting (hazard ratio 0.67, 95% confidence interval 0.49–0.91, P = 0.009). Furthermore, the combined prostate‐specific antigen progression‐free survival was significantly longer in the abiraterone‐to‐enzalutamide sequence than in the enzalutamide‐to‐abiraterone sequence (hazard ratio 0.56, 95% confidence interval 0.41–0.76, P < 0.001). The difference was significant even in multivariate analyses (hazard ratio 0.65, 95% confidence interval 0.42–0.99, P = 0.044). There was no statistical difference in overall survival between the two sequences in univariate (hazard ratio 0.88, 95% confidence interval 0.53–1.43, P = 0.599) and multivariate analyses (hazard ratio 0.81, 95% confidence interval 0.49–1.35, P = 0.427).ConclusionsThe abiraterone‐to‐enzalutamide sequence might have more favorable efficacy in terms of combined prostate‐specific antigen progression‐free survival than the enzalutamide‐to‐abiraterone sequence, although no differences in overall survival were observed. This could possibly be attributable to longer prostate‐specific antigen progression‐free survival with second‐line enzalutamide compared with abiraterone.