bluuebunny/crossref_metadata_2025_split huggingface dataset:
Broken force dispersal network in tip-links by the mutations induces hearing-loss
Authors: Hazra Jagadish P. , Sagar Amin , Arora Nisha , Deb Debadutta , Kaur Simerpreet , Rakshit Sabyasachi 
Published: April 2019

AbstractTip-link as force-sensor in the hearing conveys the mechanical force originating from sound to ion-channels while maintaining the integrity of the entire sensory assembly in inner-ear. This delicate balance between structure and function of tip-links is regulated by Ca2+-ions present in endolymph. Mutations at the Ca2+-binding sites of tip-links often lead to congenital deafness, sometimes syndromic defects impairing vision along with hearing. Although such mutations are already identified, it is still not clear how the mutants alter the structure-function properties of the force-sensors associated with diseases. With an aim to decipher the differences in force-conveying properties of the force-sensors in molecular details, we identified the conformational variability of mutant and wild-type tip-links at the single-molecule level using FRET at the endolymphatic Ca2+ concentrations and subsequently measured the force-responsive behavior using single-molecule force spectroscopy with an AFM. AFM allowed us to mimic the high and wide range of force ramps (103 - 106 pN.s−1) as experienced in the inner ear. We performed in silico network analyses to learn that alterations in the conformations of the mutants interrupt the natural force-propagation paths through the sensors and make the mutant tip-links vulnerable to input forces from sound stimuli. We also demonstrated that a Ca2+ rich environment can restore the force-response of the mutant tip-links which may eventually facilitate the designing of better therapeutic strategies to the hearing loss.Significance StatementForce-sensors in inner ear are the key components in the hearing. Mutations in force-sensors often lead to congenital hearing loss. Loss of hearing has become a threat to humanity, with over 5% of world population suffering from deafness and 40% of which is congenital, primarily due to mutations in the sensory machinery in inner-ear. A better understanding of the molecular mechanism of the underlined hearing loss due to mutations is, therefore, necessary for better therapeutics to deaf. Here with a zoomed region of the force-sensors, we pointed out the differences in the force-propagation properties of the mutant and wild-type force-sensors. Our observation on restoring of functions of mutants in Ca2+-rich buffer indicates methods of developing low-cost therapeutic strategies against deafness.
A Plant-Specific Polarity Module Establishes Cell Fate Asymmetry in the Arabidopsis Stomatal Lineage
Authors: Rowe Matthew H. , Dong Juan , Weimer Annika K. , Bergmann Dominique C. 
Published: April 2019

SUMMARYGenerating cell polarity in anticipation of asymmetric cell division is required in many developmental contexts across a diverse range of species. Physical and genetic diversity among major multicellular taxa, however, demand different molecular solutions to this problem. The Arabidopsis stomatal lineage displays asymmetric, stem cell-like and oriented cell divisions, which require the activity of the polarly localized protein, BASL. Here we identify the plant-specific BREVIS RADIX (BRX) family as localization and activity partners of BASL. We show that members of the BRX family are polarly localized to peripheral domains in stomatal lineage cells and that their collective activity is required for asymmetric cell divisions. We further demonstrate a mechanism for these behaviors by uncovering mutual, yet unequal dependencies of BASL and the BRX family for each other’s localization and segregation at the periphery of stomatal lineage cells.
Functional promoter polymorphisms govern the differential expression of HMG-CoA Reductase gene in rat models of essential hypertension
Authors: Khan Abrar A. , Sundar Poovitha , Gupta Vinayak , Arige Vikas , Reddy S. Santosh , Dikshit Madhu , Barthwal Manoj K. , Mahapatra Nitish R. 
Published: April 2019

ABSTRACT3-Hydroxy-3-methyl glutaryl-coenzyme A reductase (Hmgcr) encoding the rate-limiting enzyme in the cholesterol biosynthesis pathway is a candidate gene for essential hypertension (EH). However, the regulation ofHmgcrin rat models of hypertension (viz. Spontaneously Hypertensive Rats [SHR] and its normotensive control Wistar/Kyoto [WKY] strain) is unknown. Here, we show that Hmgcr transcript and protein levels are diminished in liver tissues of SHR as compared to WKY. Consistently, a number of other rat models of hypertension display diminished cholesterol levels as compared to corresponding control strains. Sequencing of theHmgcrpromoter in SHR/WKY reveals three variations: A-405G, C-62T and a 11 bp insertion (-393_-382insTGCGGTCCTCC) in SHR. Moreover, SHR-Hmgcrpromoter displays higher activity than WKY-Hmgcrpromoter in various cell lines. Transient transfections ofHmgcr-promoter mutants andin silicoanalysis suggest altered binding of Runx3 and Srebf1 across A-405G and -393_-382insTGCGGTCCTCC sites. Indeed, chromatin immunoprecipitation assays confirm differential binding of Runx3/Srebf1 toHmgcrpromoter leading to diminished expression ofHmgcrin SHR as compared to WKY under basal/cholesterol-modulated conditions. Taken together, this study provides mechanistic insights for the alteredHmgcrexpression in these models of EH, thereby unravelling the links of this gene to hypertension and associated cardiovascular disease states.
Experience-dependent development and maintenance of binocular neurons in the mouse visual cortex
Authors: Jenks Kyle R. , Shepherd Jason D. 
Published: April 2019

ABSTRACTThe normal development of neuronal circuits requires both hard-wired gene expression and experience. Sensory processing, such as vision, is especially sensitive to perturbations in experience. However, the exact contribution of experience to neuronal visual response properties and binocular vision remains unknown. To determine how visual response properties developin vivo, we used single cell resolution two-photon calcium imaging of mouse binocular visual cortex at multiple time-points after eye opening. Few neurons are binocularly responsive immediately after eye opening and respond solely to either the contralateral or ipsilateral eye. Binocular neurons emerge during development, which requires visual experience, and show specific tuning of visual response properties. As binocular neurons emerge, activity between the two eyes becomes more correlated in the neuropil. Since experience-dependent plasticity requires the expression of activity-dependent genes, we determined whether the plasticity geneArcmediates the development of normal visual response properties. Surprisingly, rather than mirroring the effects of visual deprivation, mice that lackArcshow increased numbers of binocular neurons during development. Strikingly, removingArcin adult binocular visual cortex increases the numbers of binocular neurons and recapitulates the developmental phenotype, suggesting cortical circuits that mediate visual processing require ongoing experience-dependent plasticity. Thus, experience is critical for the normal development and maintenance of circuits required to process binocular vision.
Are agri‐environment schemes successful in delivering conservation grazing management on saltmarsh?
Authors: Mason Lucy R. , Feather Alastair , Godden Nick , Vreugdenhil Chris C. , Smart Jennifer 
Published: April 2019

Abstract

Grasslands occur around the globe and, in temperate regions, their natural management by fire, drought and wild herbivores has largely been replaced by grazing with domestic livestock. Successful management for agriculture is not always suitable for conservation and can have a detrimental effect on biodiversity. Conservation grazing of saltmarshes, delivered through agri‐environment schemes, may provide a solution to counteract biodiversity loss by providing farmers with financial incentives to graze these internationally important coastal wetlands more sensitively.

To assess whether conservation grazing is being achieved and whether agri‐environment schemes are effective in delivering this management, we conducted a national survey on English saltmarshes, scoring the management on each site as optimal, suboptimal or detrimental in terms of suitability for achieving conservation aims for five aspects of grazing: presence, stock type, intensity, timing and habitat impact.

Although most saltmarshes suitable for grazing in England were grazed, conservation grazing was not being achieved. Sites under agri‐environment management for longer did score higher and approached optimal levels in terms of grazing intensity in one region, but sites with agri‐environment agreements were no more likely to be grazed at optimal conservation levels than sites without them overall, indicating that agri‐environment schemes, in their current form, are an ineffective delivery mechanism for conservation grazing on saltmarsh.

The low specificity of agri‐environment prescription wording may contribute to this failure, with prescriptions either being vague or specifying suboptimal or detrimental management objectives, particularly for grazing intensity, timing and stock type. These objectives are often set too high or too low, during unsuitable periods or using stock types inappropriate for achieving conservation aims.

Synthesis and applications. Our national survey indicates that agri‐environment schemes are not currently delivering conservation grazing on English saltmarshes. Agri‐environment schemes are the only mechanism through which such grazing can be implemented on a national scale, so improving their effectiveness is a priority. Policymakers, researchers and managers need to work together to ensure better translation of conservation guidelines into schemes, increasing the specificity of management prescriptions and improving understanding of the need for management measures. A more detailed and reliable system of auditing to ensure that management activities are taking place would be beneficial or alternatively moving to a results‐based scheme where payments are made on desirable outcomes rather than on evidence of management.
The pathophysiology of the septate uterus: a systematic review
Authors: Rikken JFW , Leeuwis‐Fedorovich NE , Letteboer S , Emanuel MH , Limpens J , van der Veen F , Goddijn M , van Wely M 
Published: April 2019

BackgroundLittle is known about the pathophysiology underlying the increased risk for impaired reproductive outcomes in women with a septate uterus.ObjectivesWe explored the available evidence on the pathophysiology of the septate uterus in an attempt to find a biological basis for these effects.Search strategyWe performed a systematic literature search in OVID MEDLINE and OVID EMBASE from inception to January 2018.Selection criteriaWe selected studies that investigated the pathophysiology of the septate uterus. Case reports or reviews without original data were excluded.Data collection and analysisTwo reviewers independently evaluated potentially eligible papers.Main resultsThirty‐eight studies were included for analysis. The overall findings were that the intrauterine septum consists of endometrium and myometrium similar to the uterine wall. All five imaging studies that evaluated vascularity found that most of the intrauterine septa were vascularised. Histological studies found that the intrauterine septum consisted of myometrium and was covered by endometrium (n = 9). The endometrium covering the septum showed differences in histological composition in four studies and in gene expression in three studies compared with the normal uterine wall.ConclusionsWe found no clear biological basis for the impaired reproductive outcomes in women with a septate uterus. Either the gross anatomy of the septum itself or differences in histology or gene expression of the septum could account for the increased risk of reproductive waste observed after implantation in the septum.Tweetable abstractIn women with a septate uterus differences in histology or gene expression could account for impaired reproductive outcome.
High accruals momentum
Authors: Hao Xiaoting , Jang Juwon , Lee Eunju 
Published: April 2019

AbstractWe examine the information content of high accruals momentum defined as a string of high discretionary accruals for four consecutive years. We find that firms that consistently report high levels of discretionary accruals experience low subsequent returns. The results are robust after we control for annual levels of discretionary accruals for the estimation period of high accruals momentum. Furthermore, the predictive power of the high accruals momentum for future returns is strongly persistent even after the existing accruals anomaly disappears. Our results also show that the high accruals momentum impact is more pronounced for low growth firms, suggesting that the overpricing of stocks with high accruals momentum is driven by managerial discretion to manage earnings.
Population reinforcement accelerates subadult recruitment rates in an endangered freshwater turtle
Authors: Carstairs S. , Paterson J. E. , Jager K. L. , Gasbarrini D. , Mui A. B. , Davy C. M. 
Published: April 2019

AbstractWildlife diversity and abundance are declining globally and population reinforcement with captive‐reared animals is a common intervention used to prevent extinctions. Released captive‐reared individuals may undergo an acclimation period before their behavior and success is comparable to wild‐reared individuals because they lack experience with predators, complex habitats and variable environmental conditions. Quantifying post‐release acclimation effects on fitness and behavior is important for maximizing the success of reintroduction programs and for predicting the number of captive‐reared animals required for release. Endangered Blanding's turtles Emydoidea blandingii exhibit low recruitment and may benefit from population reinforcement with captive‐reared, ‘headstarted’ individuals (headstarts). We used 6 years of data to compare survival, growth, habitat use and movement ecology between wild‐hatched juvenile turtles and headstarts reared from eggs rescued from injured females. We found strong evidence of an acclimation effect in headstarts, with lower movement, growth, and survival during the first one to two years post‐release. Following this acclimation period, headstarts had movement, growth and survival similar to wild‐hatched juveniles. Habitat use did not differ between headstarts and wild‐hatched juveniles. We hypothesize that the acclimation period occurred because headstarts were introduced directly into the wild (i.e. ‘hard release’) and that providing additional support before or after release may improve the success of headstarts. Headstarts had a monthly survival probability of 0.89 in the first year post‐release, and 0.98 after the first year post‐release. We estimated that headstarts at our sites have approximately three times higher probability of surviving to 10 years of age, compared to wild‐hatched individuals at other sites. Our results highlight that headstarts should be released into habitat individually rather than in clusters, and highlight the need to investigate whether post‐release mortality of captive‐reared animals could be mitigated by increased acclimation to wild conditions, for example through prerelease periods in outdoor pens.
Spatio‐temporal gradients in food supply help explain the short‐term colonisation dynamics of the critically endangered central rock‐rat (Zyzomys pedunculatus)
Authors: Nano Catherine E. M. , Randall Debbie J. , Stewart Alistair J. , Pavey Chris R. , McDonald Peter J. 
Published: April 2019

AbstractCurrently, the impact of introduced predators on small mammal population decline is a focal research direction in the Australian desert literature. In all likelihood though, single‐factor explanation of population dynamics is inadequate, leaving gaps in our knowledge of the multitude of potential influences on small mammal abundance and occupancy patterns in time and space. Here, we investigated floristic gradients across four potential refuge sites of the central rock‐rat, Zyzomys pedunculatus, a granivore rodent (50–120 g) that is endemic to central Australia and is categorised as critically endangered. The study took place in Tjoritja/West MacDonnell National Park in the MacDonnell Ranges bioregion. Floristic sampling was allocated across the four sites, the locations of which were predetermined by an established monitoring and management programme for the central rock‐rat. Our aim was to examine the relationship between environmental gradients and floristic composition across the four sites, and thereby test the extent to which the patterns of food type and food availability can inform central rock‐rat spatio‐temporal dynamics. We found high site‐scale floristic patterning that related foremost to elevation and then to antecedent rainfall and time‐since‐fire and fire‐severity effects. To interpret these results, we applied the principles of refuge theory and we described a gradient from core refuge habitat to intermittent and then marginal habitat within the current central rock‐rat stronghold area. Overall, our results implied a strong floristic basis to central rock‐rat site occurrence, and they thus compel us to take explicit account of spatial (elevation) and temporal (rainfall–productivity and fire‐disturbance) influences on the food axis of potential refuge sites of this critically endangered species.
Retracted: Role of the immune system in vascular function and blood pressure control induced by faecal microbiota transplantation in rats
Authors: Toral Marta , Robles‐Vera Iñaki , de la Visitación Néstor , Romero Miguel , Sánchez Manuel , Gómez‐Guzmán Manuel , Rodriguez‐Nogales Alba , Yang Tao , Jiménez Rosario , Algieri Francesca , Gálvez Julio , Raizada Mohan K , Duarte Juan 
Published: April 2019

AbstractAimHigh blood pressure (BP) is associated with gut microbiota dysbiosis. The aim of this study was to investigate whether changes in gut microbiota induced by exchanging the gut microbiota between spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto (WKY) alter the gut‐immune system interaction inducing changes in vascular function and BP.MethodsTwenty‐week‐old recipient WKY and SHR were orally gavaged with donor faecal contents from WKY or SHR. In additional experiments, we used a design to determine whether blockade of B7‐dependent costimulation with CTLA4‐Ig or blockade of IL‐17 with IL‐17‐neutralizing antibody could prevent hypertension caused by faecal microbiota transplantation (FMT) from SHR to WKY.ResultsCorrelation analyses identified the bacterial abundance of Turicibacter and S24‐7_g that, respectively, positively and negatively correlated with systolic BP. FMT from WKY rats to SHR rats reduced basal systolic BP, restored the imbalance between Th17/Treg in mesenteric lymph nodes (MLNs) and aorta, and improved endothelial dysfunction and vascular oxidative status found in SHR transplanted with SHR faeces. FMT from SHR to WKY increased CD80 and CD86 mRNA levels and T cells activation in MLNs, circulating T cells, aortic T cell infiltration, impaired endothelial function and increased basal SBP. These effects were abolished by blockade of B7‐dependent costimulation with CTLA4‐Ig. IL‐17a neutralizing antibody reduced SBP and improved endothelial dysfunction induced by FMT from SHR to WKY.ConclusionGut microbiota is an important factor involved in the control of BP, as a consequence of its effect in T‐cell activation in gut immune system and vascular T‐cells accumulation.
Examining family and school factors as predictors of delinquency: A study of juvenile offenders, at‐risk students, and low‐risk students in Malaysia
Authors: Tan Bee Piang , Zuraini Jamil @ Osman , Noor Banu Mahadir Naidu 
Published: April 2019

AbstractThis study aims to examine family and school factors as predictors of delinquency among adolescents in Malaysia. A total of 101 juvenile offenders, 86 at‐risk students, and 92 low‐risk students were involved in this study. Multinomial logistic regression was used to predict the likelihood of an adolescent being in a group of juvenile offenders or of being an at‐risk or low‐risk student, based on four predictor variables: family structure, family relationships, school relationships, and commitment to learning. The results show that family relations, school relations, and commitment to learning have different predictive effects on the likelihood of different levels of delinquent behavior. However, family structure is not found to be a significant predictor in the logistic regression in this study. The findings of the study suggest that keeping young people in school can serve as a strong protective factor that serves to prevent at‐risk students from moving along the trajectory of serious delinquent behaviors.
Agitated depression in bipolar disorder
Authors: Serra Francesca , Gordon‐Smith Katherine , Perry Amy , Fraser Christine , Di Florio Arianna , Craddock Nick , Jones Ian , Jones Lisa 
Published: April 2019

AbstractObjectivesIt has been suggested that agitated depression (AD) is a common, severe feature in bipolar disorder. We aimed to estimate the prevalence of AD and investigate whether presence of AD was associated with episodic and lifetime clinical features in a large well‐characterized bipolar disorder sample.MethodThe prevalence of agitation, based on semi‐structured interview and medical case‐notes, in the most severe depressive episode was estimated in 2925 individuals with DSM‐IV bipolar disorder recruited into the UK Bipolar Disorder Research Network. Predictors of agitation were ascertained using symptoms within the same episode and lifetime clinical features using multivariate models.Results32.3% (n = 946) experienced agitation during the worst depressive episode. Within the same episode, significant predictors of presence of agitation were: insomnia (OR 2.119, P < 0.001), poor concentration (OR 1.966, P = 0.027), decreased libido (OR 1.960, P < 0.001), suicidal ideation (OR 1.861, P < 0.001), slowed activity (OR 1.504, P = 0.001), and poor appetite (OR 1.297, P = 0.029). Over the lifetime illness course, co‐morbid panic disorder (OR 2.000, P < 0.001), suicide attempt (OR 1.399, P = 0.007), and dysphoric mania (OR 1.354, P = 0.017) were significantly associated with AD.ConclusionsAgitation accompanied bipolar depression in at least one‐third of cases in our sample and was associated with concurrent somatic depressive symptoms, which are also common features of mixed manic states. Furthermore, AD in our sample was associated with lifetime experience of mixed mania, in addition to severe lifetime illness course including comorbid panic disorder and suicidal behavior. Our results have implications for the diagnosis and treatment of agitated features in bipolar depression.