bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial biofilm formation on soil fungi: a widespread ability under controls
Authors: Guennoc Cora Miquel , Rose Christophe , Labbé Jessy , Deveau Aurélie
Published: April 2017

In natural environments, bacteria preferentially live in biofilms that they build on abiotic surfaces but also on living tissues. Although fungi form extensive networks of hyphae within soils and thus could provide immense surfaces for bacteria to build biofilms and to proliferate, the extent on such phenomenon and the consequences for the fitness of both microorganisms is poorly known in soils. Here, we analyzed the process of formation of biofilms by various bacteria on hyphae of soil fungi in anin vitrosetting using confocal and electron microscopy. We showed that the ability to form biofilms on fungal hyphae is widely shared among soil bacteria. In contrast, some fungi, mainly belonging to the Ascomycete class, did not allow for the formation of bacterial biofilms on their surfaces. The formation of biofilms was also strongly modulated by the presence of tree roots and by the development of the ectomycorrhizal symbiosis, suggesting that biofilm formation does not occur randomly in soil but that it is highly regulated by several biotic factors. Finally, our study led to the unexpected finding that networks of filaments made of extracellular DNA were used to build the skeleton of biofilms by a large array of bacteria.
Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (Danio rerio)
Authors: Cong Lin , Wang Zeguan , Chai Yuming , Hang Wei , Shang Chunfeng , Yang Wenbin , Bai Lu , Du Jiulin , Wang Kai , Wen Quan
Published: April 2017

The internal brain dynamics that link sensation and action are arguably better studied during natural animal behaviors. Here we report on a novel volume imaging and 3D tracking technique that monitors whole brain neural activity in freely swimming larval zebrafish (Danio rerio). We demonstrated the capability of our system through functional imaging of neural activity during visually evoked and prey capture behaviors in larval zebrafish.
Altered expression of a unique set of genes reveals complex etiology of Schizophrenia
Authors: Kumar Ashutosh , Singh Himanshu Narayan , Pareek Vikas , Raza Khursheed , Kumar Pavan , Faiq Muneeb A. , Mochan Sankat , Dantham Subrahamanyam , Upadhyaya Ashish Datt
Published: April 2017

Purpose

The etiology of schizophrenia is extensively debated, and multiple factors have been contended to be involved. A panoramic view of the contributing factors in a genome-wide study can be an effective strategy to provide a comprehensive understanding of its causality.

Materials and Methods

GSE53987 dataset downloaded from GEO-database, which comprised mRNA expression data of post-mortem brain tissue across three regions from control and age-matched subjects of schizophrenia (N= Hippocampus (HIP): C-15, T-18, Prefrontal cortex (PFC): C-15, T-19, Associative striatum (STR): C-18, T-18). Bio-conductor-affy-package used to compute mRNA expression, and further t-test applied to investigate differential gene expression. The analysis of the derived genes performed using PANTHER Classification System and NCBI database.

Results

A set of 40 genes showed significantly altered (p<0.01) expression across all three brain regions. The analyses unraveled genes implicated in biological processes and events, and molecular pathways relating basic neuronal functions.

Conclusions

The deviant expression of genes maintaining basic cell machinery explains compromised neuronal processing in SCZ.

Abbreviations

Schizophrenia (SCZ), Hippocampus (HIP), Associative striatum (STR), Prefrontal cortex (PFC)
Fast and simple analysis of MiSeq amplicon sequencing data with MetaAmp
Authors: Dong Xiaoli , Kleiner Manuel , Sharp Christine E. , Thorson Erin , Li Carmen , Liu Dan , Strous Marc
Published: April 2017

Microbial community profiling by barcoded 16S rRNA gene amplicon sequencing currently has many applications in microbial ecology. The low costs of the parallel sequencing of multiplexed samples, combined with the relative ease of data processing and interpretation (compared to shotgun metagenomes) have made this an entry-level approach. Here we present the MetaAmp pipeline for processing of SSU rRNA gene and other non-coding or protein-coding amplicon sequencing data by investigators that are inexperienced with bioinformatics procedures. It accepts single-end or paired-end sequences in fasta or fastq format from various sequencing platforms. It includes read quality control, and merging of forward and reverse reads of paired-end reads. It makes use of UPARSE, Mothur, and the SILVA database for clustering, removal of chimeric reads, taxonomic classification and generation of diversity metrics. The pipeline has been validated with a mock community of known composition. MetaAmp provides a convenient web interface as well as command line interface. It is freely available at:http://ebg.ucalgary.ca/metaamp. Since its launch two years ago, MetaAmp has been used >2,800 times, by many users worldwide.
Genomic and chromatin features shaping meiotic double-strand break formation and repair in mice
Authors: Yamada Shintaro , Kim Seoyoung , Tischfield Sam E. , Lange Julian , Jasin Maria , Keeney Scott
Published: April 2017

The SPO11-generated DNA double-strand breaks (DSBs) that initiate meiotic recombination occur non-randomly across genomes, but mechanisms shaping their distribution and repair remain incompletely understood. Here, we expand on recent studies of nucleotide-resolution DSB maps in mouse spermatocytes. We find that trimethylation of histone H3 lysine 36 around DSB hotspots is highly correlated, both spatially and quantitatively, with trimethylation of H3 lysine 4, consistent with coordinated formation and action of both PRDM9-dependent histone modifications. In contrast, the DSB-responsive kinase ATM contributes independently of PRDM9 to controlling hotspot activity, and combined action of ATM and PRDM9 can explain nearly two-thirds of the variation in DSB frequency between hotspots. DSBs were modestly underrepresented in most repetitive sequences such as segmental duplications and transposons. Nonetheless, numerous DSBs form within repetitive sequences in each meiosis and some classes of repeats are preferentially targeted. Implications of these findings are discussed for evolution of PRDM9 and its role in hybrid strain sterility in mice. Finally, we document the relationship between mouse strain-specific DNA sequence variants within PRDM9 recognition motifs and attendant differences in recombination outcomes. Our results provide further insights into the complex web of factors that influence meiotic recombination patterns.
PHRED-1 is a divergent neurexin-1 homolog that organizes muscle fibers and patterns organs during regeneration
Authors: Adler Carolyn E. , Alvarado Alejandro Sánchez
Published: April 2017

Regeneration of body parts requires the replacement of multiple cell types. To dissect this complex process, we utilized planarian flatworms that are capable of regenerating any tissue after amputation. An RNAi screen for genes involved in regeneration of the pharynx identified a novel gene, Pharynx regeneration defective-1 (PHRED-1) as essential for normal pharynx regeneration. PHRED-1 is a predicted transmembrane protein containing EGF, Laminin G, and WD40 domains, is expressed in muscle, and has predicted homologs restricted to other lophotrochozoan species. Knockdown of PHRED-1 causes abnormal regeneration of muscle fibers in both the pharynx and body wall muscle. In addition to defects in muscle regeneration, knockdown of PHRED-1 or the bHLH transcription factor MyoD also causes defects in muscle and intestinal regeneration. Together, our data demonstrate that muscle plays a key role in restoring the structural integrity of closely associated organs, and in planarians it may form a scaffold that facilitates normal intestinal branching.

Graphical Abstract

Highlights

-PHRED-1 is a predicted transmembrane protein that contains Laminin G, EGF and WD40 domains

-PHRED-1 is required for normal muscle patterning during regeneration

-phred-1is expressed in muscle cells

-Muscle forms an essential scaffold for regeneration
How convincing is a matching Y-chromosome profile?
Authors: Andersen Mikkel M , Balding David J
Published: April 2017

The introduction of forensic autosomal DNA profiles was controversial, but the problems were successfully addressed, and DNA profiling has gone on to revolutionise forensic science. Y-chromosome profiles are valuable when there is a mixture of male-source and female-source DNA, and interest centres on the identity of the male source(s) of the DNA. The problem of evaluating evidential weight is even more challenging for Y profiles than for autosomal profiles. Numerous approaches have been proposed, but they fail to deal adequately with the fact that men with matching Y-profiles are re-lated in extended patrilineal clans, many of which may not be represented in available databases. This problem has been exacerbated by recent profiling kits with high mutation rates. Because the relevant population is difficult to define, yet the number of matching relatives is fixed as population size varies, it is typically infeasible to derive population-based match probabilities relevant to a specific crime. We propose a conceptually simple solution, based on a simulation model and software to approximate the distribution of the number of males with a matching Y profile. We show that this distribution is robust to different values for the variance in reproductive success and the population growth rate. We also use importance sampling reweighting to derive the distribution of the number of matching males conditional on a database frequency, finding that this conditioning typically has only a modest impact. We illustrate the use of our approach to quantify the value of Y profile evidence for a court in a way that is both scientifically valid and easily comprehensible by a judge or juror.
High-resolution mapping of heteroduplex DNA formed during UV-induced and spontaneous mitotic recombination events in yeast
Authors: Yin Yi , Dominska Margaret , Yim Eunice , Petes Thomas D.
Published: April 2017

Double-stranded DNA breaks (DSBs) can be generated by both endogenous and exogenous agents. In diploid yeast strains, such breaks are usually repaired by homologous recombination (HR), and a number of different HR pathways have been described. An early step for all HR pathways is formation of a heteroduplex, in which a single-strand from the broken DNA molecule pairs with a strand derived from an intact DNA molecule. If the two strands of DNA are not identical, within the heteroduplex DNA (hetDNA), there will be mismatches. In a wild-type strain, these mismatches are removed by the mismatch repair (MMR) system. In strains lacking MMR, the mismatches persist and can be detected by a variety of genetic and physical techniques. Most previous studies involving hetDNA formed during mitotic recombination have been restricted to a single locus with DSBs induced at a defined position by a site-specific endonuclease. In addition, in most of these studies, recombination between repeated genes was examined; in such studies, the sequence homologies were usually less than 5 kb. In the present study, we present a global mapping of hetDNA formed in a UV-treated MMR-defectivemlh1strain. Although about two-thirds of the recombination events were associated with hetDNA with a continuous array of unrepaired mismatches, in about one-third of the events, we found regions of unrepaired mismatches flanking regions without mismatches. We suggest that these discontinuous hetDNAs involve template switching during repair synthesis, repair of a double-stranded DNA gap, and/or Mlh1-independent MMR. Many of our observed events are not explicable by the simplest form of the double-strand break repair (DSBR) model of recombination. We also studied hetDNA associated with spontaneous recombination events selected on chromosomes IV and V in a wild-type strain. The interval on chromosome IV contained a hotspot for spontaneous crossovers generated by an inverted pair of transposable elements (HS4). We showed that HS4-induced recombination events are associated with the formation of very large (>30 kb) double-stranded DNA gaps.
On Neural Code – The Self-Information Processor disguised as neuronal variability?
Authors: Tsien Joe Z. , Li Meng
Published: April 2017

One 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

The 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 SUMMARY

The 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

Erythrocytes 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

Mitotic 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

We 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

Cold 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.

Highlights

Blood 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.

ETOC

Simcox 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 Abstract

Cold 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

Senescent 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

We 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

Mainland 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

We 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

In 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

Aim

This 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.

Methods

Rats 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.

Results

The 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.

Conclusion

Obesity 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

Aim

To 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.

Methods

We 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).

Results

According 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.

Conclusions

The 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

Objectives

To evaluate and compare the efficacy of sequential treatment with abiraterone followed by enzalutamide or vice versa for castration‐resistant prostate cancer.

Methods

We 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.

Results

Overall, 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).

Conclusions

The 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.
Assessment of sexual function in Japanese men with prostate cancer undergoing permanent brachytherapy without androgen deprivation therapy: Analysis from the Japanese Prostate Cancer Outcome Study of Permanent Iodine‐125 Seed Implantation database
Authors: Okihara Koji , Yorozu Atsunori , Saito Shiro , Tanaka Nobumichi , Koga Hirofumi , Higashide Satoshi , Kikuchi Takashi , Nakano Masahiro
Published: April 2017

Objectives

To evaluate male sexual function in Japanese prostate cancer patients undergoing permanent brachytherapy without endocrine treatment, using quality of life measures of the Expanded Prostate Cancer Index Composite.

Methods

A total of 482 patients were selected as analysis subjects from the nationwide database for the Japanese Prostate Cancer Outcome Study of Permanent Iodine‐125 Seed Implantation. The patients were asked to complete the Expanded Prostate Cancer Index Composite questionnaires before and at 3, 12, 24, and 36 months after the permanent brachytherapy. Changes in their responses were analyzed, and any association of the outcomes was investigated. Furthermore, changes over time in their answers to Q18 (usual quality of your erections) were analyzed.

Results

A total of 72 patients (14.9%) had received external beam radiation. A total of 68 patients (14.1%) had taken any 5‐phosphodiesterase inhibitor medications. Regarding Q18, 232 patients (48.2%) selected either “There was no sexual activity” or “There was no desire for erection” before receiving permanent brachytherapy. Of all the 482 patients, sexual function was preserved in 138 patients (28.7%) 3 years after permanent brachytherapy. Overall satisfaction has significantly improved without regard for the deterioration of sexual function. Significant factors for maintaining sexual activity were patient age and sexual activity before permanent brachytherapy.

Conclusions

In Japanese patients undergoing permanent brachytherapy alone for prostate cancer, the sexual function is not well preserved. However, decreased sexual function does not seem to represent a major factor determining patients’ overall satisfaction. These findings might be peculiar to Japanese patients, in whom elderly subjects account for the majority.
Tool use in neurodegenerative diseases: Planning or technical reasoning?
Authors: Baumard Josselin , Lesourd Mathieu , Remigereau Chrystelle , Jarry Christophe , Etcharry‐Bouyx Frédérique , Chauviré Valérie , Osiurak François , Le Gall Didier
Published: April 2017

Recent works showed that tool use can be impaired in stroke patients because of either planning or technical reasoning deficits, but these two hypotheses have not yet been compared in the field of neurodegenerative diseases. The aim of this study was to address the relationships between real tool use, mechanical problem‐solving, and planning skills in patients with Alzheimer's disease (AD, n = 32), semantic dementia (SD, n = 16), and corticobasal syndrome (CBS, n = 9). Patients were asked to select and use ten common tools, to solve three mechanical problems, and to complete the Tower of London test. Motor function and episodic memory were controlled using the Purdue Pegboard Test and the BEC96 questionnaire, respectively. A data‐transformation method was applied to avoid ceiling effects, and single‐case analysis was performed based on raw scores and completion time. All groups demonstrated either impaired or slowed tool use. Planning deficits were found only in the AD group. Mechanical problem‐solving deficits were observed only in the AD and CBS groups. Performance in the Tower of London test was the best predictor of tool use skills in the AD group, suggesting these patients had general rather than mechanical problem‐solving deficits. Episodic memory seemed to play little role in performance. Motor dysfunction tended to be associated with tool use skills in CBS patients, while tool use disorders are interpreted as a consequence of the semantic loss in SD in line with previous works. These findings may encourage caregivers to set up disease‐centred interventions.
Effect on Rendement Napole genotype on metabolic markers in Ossabaw pigs fed different levels of fat
Authors: Lu H. , Yan H. , Ward M. G. , Stewart T. , Adeola O. , Ajuwon K. M.
Published: April 2017

We investigated effects of Rendement Napole (RN) genotype on metabolic markers in Ossabaw pigs fed diets with different levels of dietary fat. Thirty‐two pigs, belonging to either the wild‐type (WT, rn+/rn+) or carrier (CAR, RN−/rn+) genotypes (n = 16/genotype), were divided into two dietary groups, (high fat [HF] or low fat [LF]) diets, for 12 weeks (n = 8 pigs/genotype/diet) after which pigs were killed for gene expression analysis by RT‐PCR. Feeding HF diet caused increased daily gain (ADG, p < .05) and final body weight (BW) (p < .05) in comparison with the LF diet (p < .05). Feed efficiency (gain:feed) was higher (p < .05) in pigs on the HF and was higher (p < .05) in CAR pigs compared to WT. There was genotype × diet interaction (p = .05) on final BW such that CAR animals on LF diet had the same final BW as animals of both genotypes on HF diet. Carrier pigs on LF diet had higher (p < .05) average daily gain and gain:feed than WT pigs. There was a trend (p < .08) for a higher feed consumption in pigs on the LF diet. Backfat thickness was higher (p < .01) in pigs on the HF diet. Serum triglyceride was higher (0.62 vs. 0.33 mg/dl, p < .01) in pigs on HF diet. Serum insulin was higher (p < .05) in CAR versus WT pigs (0.40 vs. 0.015 μg/ml). Pigs on the HF diet had a higher (p < .05) serum insulin compared to those on the LF diet (0.032 vs. 0.023 μg/ml). Carnitine palmitoyl transferase 1‐alpha was higher (p < .05) in the longissimus dorsi and semitendinosus muscles of pigs on HF diet. Acyl‐CoA oxidase I was elevated (p < .05) in the liver of pigs on HF diet. Fatty acid synthase was lower in the longissimus dorsi muscle, liver and mesenteric fat (p < .05) of carrier pigs. The RN gene regulates specific metabolic markers in the Ossabaw pigs.
Exogenous protease supplementation of poultry by‐product meal‐based diets for broilers: Effects on growth, carcass characteristics and nutrient digestibility
Authors: Mahmood T. , Mirza M. A. , Nawaz H. , Shahid M.
Published: April 2017

An experiment was conducted to investigate the effects of three levels (0%, 3% and 6%) of poultry by‐product meal (PBM) with or without protease on broiler growth, carcass characteristics and nutrient digestibility from 1 to 35 days. Two hundred and forty birds (n = 240) were fed equi‐caloric and equi‐nitrogenous (ME 2850 kcal/kg; CP 20%) diets throughout the experiment. The enzyme supplementation increased feed intake (p < .01) and body weight gain (p < .01), but feed:gain remained unaffected (p > .05) from 1 to 21 days. Increasing level of PBM decreased feed intake (p < .05), but body weight gain was improved (p < .05) at 3% PBM level during 1 to 21 days. The feed:gain was improved (p < .05) in birds fed diets containing 3% PBM. The feed:gain was also improved in birds fed diets containing 3% PBM from 1 to 35 days. However, feed intake and body weight gain in birds fed diets containing PBM remained unaffected. An interaction (p < .01) on feed intake between enzyme and PBM was noticed during 1 to 21 days. However, no interaction was recorded for body weight gain and feed:gain. The per cent carcass yield improved (p < .01) in birds fed diets supplemented with enzyme. The per cent breast meat yield was depressed (p < .005) in birds fed diets containing PBM. Apparent metabolizable energy (p < .001), nitrogen retention (p < .01), apparent metabolizable energy corrected for nitrogen (p < .001), and apparent digestibility coefficient for nitrogen (p < .01) improved in birds fed diets containing enzyme; however, a reverse was noticed in those fed diets containing only PBM. In conclusion, inclusion of 3% PBM along with supplementation of exogenous protease improved performance and nutrient digestibility in broilers.
Dietary pea fibre alters the microbial community and fermentation with increase in fibre degradation‐associated bacterial groups in the colon of pigs
Authors: Luo Y. , Chen H. , Yu B. , He J. , Zheng P. , Mao X. , Yu J. , Luo J. , Huang Z. , Chen D.
Published: April 2017

This study was attempted to investigate the influence of dietary pea fibre (PF) on the community and quantity of colonic bacteria of piglets and finisher pigs using pyrosequencing data and real‐time PCR. The concentration of acetate in colonic digesta from PF‐fed piglets was significantly higher than that from control (p < .05). Feeding PF diet to finisher pigs increased the ratio of acetate to total volatile fatty acids (VFAs) but decreased the ratio of butyrate, as compared with the control pigs (p < .05 in both cases). The lower ratio of butyrate in samples from finisher pigs receiving PF suggested that this dietary fibre did not favour butyrate production in the hindgut. Supplementation of PF to piglets reduced abundance of Bacteroidetes, as compared with control animals. However, PF had opposite effects in finisher pigs, higher abundance of Bacteroidetes but lower of Firmicutes. Lactobacillus and Prevotella were found as the predominant genera in PF piglets. Prevotella accounted for nearly half of the total bacteria in the colon of finisher pigs in the PF group, but only one‐third in the control animals. Quantitative PCR showed that Firmicutes/Bacteroidetes were significantly increased in the colon of PF piglets (p < .05) as compared with control animals, but decreased in PF finisher pigs. Bacteroidetes–Prevotella–Porphyromonas and Desulfovibrio desulfuricans which are involved in degradation of dietary fibres were more abundant in the PF finisher pigs than in the controls (p < .05), suggesting mutualism between host and its gut microbes.
Assessment of Left Atrial Deformation and Function by 2‐Dimensional Speckle Tracking Echocardiography in Healthy Dogs and Dogs With Myxomatous Mitral Valve Disease
Authors: Baron Toaldo M. , Romito G. , Guglielmini C. , Diana A. , Pelle N.G. , Contiero B. , Cipone M.
Published: April 2017

Background

The assessment of left atrial (LA) function by 2‐dimensional speckle tracking echocardiography (STE) holds important clinical implications in human medicine. Few similar data are available in dogs.

Objectives

To assess LA function by STE in dogs with and without myxomatous mitral valve disease (MMVD), analyzing LA areas, systolic function, and strain.

Animals

One hundred and fifty dogs were divided according to the American College of Veterinary Internal Medicine classification of heart failure: 23 dogs in class A, 52 in class B1, 36 in class B2, and 39 in class C + D.

Methods

Prospective observational study. Conventional morphologic and Doppler variables, LA areas, and STE‐based LA strain analysis were performed in all dogs and results were compared among groups. Correlation analysis was carried out between LA STE variables and other echocardiographic variables.

Results

Variability study showed good reproducibility for all the tested variables (coefficient of variation <16%). Left atrial areas, fractional area change, peak atrial longitudinal strain (PALS), peak atrial contraction strain, and contraction strain index (CSI) differed significantly between groups B2 and C + D and all the other groups (overall P < .001), whereas only PALS differed between groups B1 and A (P = .01). Left atrial areas increased with progression of the disease, whereas LA functional parameters decreased. Only CSI increased nonsignificantly from group A to group B1 and then progressively decreased. Thirty‐one significant correlations (P < .001, r > .3) were found between conventional left heart echocardiographic variables and LA areas and strain variables.

Conclusions and Clinical Importance

Left atrial STE analysis provides useful information on atrial function in the dog, highlighting a progressive decline in atrial function with worsening of MMVD.