bluuebunny/crossref_metadata_2025_split huggingface dataset:
Necessary Conditions for Reliable Representation of Asynchronous Spikes Through a Single-layered Feedforward Network
Authors: Lankarany Milad 
Published: February 2019

AbstractReliable propagation of firing rate – specifically slow modulation of asynchronous spikes in fairly short time windows [20-500]ms across multiple layers of a feedforward network (FFN) receiving background synaptic noise has proven difficult to capture in spiking models. We, in this paper, explore how information of asynchronous spikes disrupted in the first layer of a typical FFN, and which factors can enable reliable information representation. Our rationale is that the reliable propagation of information across layers of a FFN is likely if that information can be preserved in the first layer of the FFN. In a typical FFN, each layer comprises a certain number (network size) of excitatory neurons – leaky integrate and fire (LIF) model neuron in this paper – receiving correlated input (common stimulus from the upstream layer) plus independent background synaptic noise. We develop a reduced network model of FFN which captures main features of a conventional all-to-all connected FFN. Exploiting the reduced network model, synaptic weights are calculated using a closed-form optimization framework that minimizes the mean squared error between reconstructed stimulus (by spikes of the first layer of FFN) and the original common stimulus. We further explore how representation of asynchronous spikes in a FFN changes with respect to other factors like the network size and the level of background synaptic noise while synaptic weights are optimized for each scenario. We show that not only synaptic weights but also the network size and the level of background synaptic noise are crucial to preserve a reliable representation of asynchronous spikes in the first layer of a FFN. This work sheds light in better understanding of how information of slowly time-varying fluctuations of the firing rate can be transmitted in multi-layered FFNs.
SynQuant: An Automatic Tool to Quantify Synapses from Microscopy Images
Authors: Wang Yizhi , Wang Congchao , Ranefall Petter , Broussard Gerard , Wang Yinxue , Shi Guilai , Wang Yue , Tian Lin , Yu Guoqiang 
Published: February 2019

AbstractMotivationSynapses are essential to neural signal transmission. Therefore, quantification of synapses and related neurites from images is vital to gain insights into the underlying pathways of brain functionality and diseases. Despite the wide availability of synapse imaging data, several issues prevent satisfactory quantification of these structures by current tools. First, the antibodies used for labeling synapses are not perfectly specific to synapses. These antibodies may exist in neurites or other cell compartments. Second, the brightness for different neurites and synapses is heterogeneous due to the variation of antibody concentration and synapse-intrinsic differences. Third, images often have low signal to noise ratio (SNR) due to constraints of experiments and availability of sensitive antibodies. The combination of these issues makes the detection of synapses challenging and necessitates developing a new tool to accurately and reliably quantify synapses.ResultsWe present an automatic probability-principled synapse detection algorithm and integrate it into our synapse quantification tool SynQuant. Derived from the theory of order statistics, our method controls the false discovery rate and improves the power of detecting synapses. Through extensive experiments on both synthetic and real images in the presence of severe antibody diffusion, high heterogeneity, and large noise, our method was demonstrated to outperform peer specialized synapse detection tools as well as generic spot detection methods by a large margin. Finally, we show SynQuant reliably uncovers statistically significant differences between disease and control conditions in a neuron-astrocyte co-culture based model of Down Syndrome.AvailabilityThe Java source code, Fiji plug-in, and test data are available at https://github.com/yu-lab-vt/SynQuant.Contactyug@vt.edu
Potential role of extracellular ATP released by bacteria in bladder infection and contractility
Authors: Abbasian Behnam , Shair Aidan , O’Gorman David B. , Pena-Diaz Ana M. , Engelbrecht Kathleen , Koenig David W. , Reid Gregor , Burton Jeremy P. 
Published: February 2019

ABSTRACTUrgency urinary incontinence (UUI), the result of conditions such as overactive bladder (OAB), could potentially be influenced by both commensal and urinary tract infection-associated bacteria. The sensing of bladder filling involves interplay between various parts of the nervous system eventually resulting in contraction of the detrusor muscle during micturition. Here we model host responses to various urogenital bacteria, firstly by using urothelial bladder cell lines and then with myofibroblast contraction assays. To measure responses, we examined calcium influx, gene expression and alpha smooth muscle actin deposition assays. We found that organisms such as Escherichia coli and Gardnerella vaginalis strongly induced calcium influx and contraction, whereas, Lactobacillus crispatus and L. gasseri did not induce this response. Additionally, supernatants from lactobacilli impeded influx-and contraction induced by the uropathogens. Upon further investigation of factors associated with the purinergic signaling pathways, we found that influx and contraction of cells correlated to the amount of extracellular ATP produced by E. coli. Certain lactobacilli appear to mitigate this response by utilizing extracellular ATP or producing inhibitory compounds which can act as a receptor agonist or calcium channel blocker. These findings suggest that members of the urinary microbiota may be influencing UUI.
First Crystal Structure of a Non-Structural Hepatitis E Viral Protein Identifies a Putative Novel Zinc-Binding Protein
Authors: Proudfoot Andrew , Hyrina Anastasia , Holdorf Meghan , Frank Andreas O. , Bussiere Dirksen 
Published: February 2019

AbstractHepatitis E virus (HEV) is a 7.2 kb positive-sense, single-stranded RNA virus containing three partially overlapping reading frames, ORF 1-3. All non-structural proteins required for viral replication are encoded by ORF1 and are transcribed as a single transcript. Computational analysis of the complete ORF1 polyprotein identified a previously uncharacterized region of predicted secondary structure bordered by two disordered regions coinciding partially with a region predicted as a putative cysteine protease. Following successful cloning, expression and purification of this region, the crystal structure of the identified protein was determined and identified to have considerable structural homology to a fatty acid binding domain. Further analysis of the structure revealed a metal binding site, shown unambiguously to specifically bind zinc via a non-classical, potentially catalytic zinc-binding motif. We present analysis for the first time of this identified non-structural protein, expanding the knowledge and understanding of the complex mechanisms of HEV biology.ImportanceHepatitis E virus (HEV) is an emerging virus found predominately in developing countries causing an estimated 20 million infections, which result in approximately 57,000 deaths a year. Although it is known that the non-structural proteins of the HEV ORF1 are expressed as a single transcript, there is debate as to whether ORF1 functions as a single polyprotein or if it is processed into separate domains via a viral or endogenous cellular protease. In the following paper, we present the first structural and biophysical characterization of a HEV non-structural protein using a construct that has partially overlapping boundaries with the predicted putative cysteine protease. Based on the structural homology of the HEV protein with known structures, along with the presence of a catalytic zinc-binding motif, it is possible that the identified protein corresponds to the HEV protease, which could require activation or repression through the binding of a fatty acid. This represents a significant step forward in the characterization and the understanding of the molecular mechanisms of the HEV genome.
Differential gene expression and the importance of regulatory ncRNAs in acidophilic microorganisms
Authors: Goltsman Daniela S. Aliaga , Hauser Loren , Dasari Mauna , Thomas Brian C. , Banfield Jillian F. 
Published: February 2019

ABSTRACTGene expression profiles provide insight into how microorganisms respond to changing environmental conditions. However, few studies have integrated expression profile analyses of both coding genes and non-coding RNAs (ncRNAs) to characterize the functional activity of microbial community members. Here, we defined gene expression profiles from environmental and laboratory-grown acidophilic biofilms using RNASeq. In total, 15.8 million Illumina reads were mapped to the genomes of 26 acidophilic microorganisms and nine viruses reconstructed from the Richmond Mine at Iron Mountain, California. More than 99% of the genome was transcribed in three Leptospirillum species, and > 80% in the archaea G-plasma and Ferroplasma Type II. High gene expression by G-plasma and the Leptospirillum Group II UBA strain correlated with extremely acidic conditions, whereas high transcriptional expression of Leptospirillum Group III and Leptospirillum Group II 5way-CG strain occurred under higher pH and lower temperature. While expression of CRISPR Cas genes occurs on the sense strand, expression of the CRISPR loci occurs on the antisense strand in the Leptospirilli. A novel riboswitch associated with the biosynthetic pathway for the osmolyte ectoine was upregulated when each specific Leptospirillum Group II strain was growing under the conditions most favorable for it. Newly described ncRNAs associated with CO dehydrogenase (CODH) suggest regulation of expression of CODH as a CO sensor in mature biofilms in the Leptospirilli. Results reveal the ways in which environmental conditions shape transcriptional profiles of organisms growing in acidophilic microbial communities and highlight the significance of ncRNAs in regulating gene expression.IMPORTANCEMicroorganisms play important roles in environmental acidification and in metal-recovery based bioleaching processes. Therefore, characterizing how actively growing microbial communities respond to different environments is key to understanding their role in those processes. Microorganisms express their genes, both coding and non-coding, differently depending on environmental factors, thus evaluating community expression profiles inform about the ecology of actively growing microorganisms. Here we used community transcriptomic analyses to characterize gene expression profiles from biofilm communities growing under extremely acidic conditions. Results expand our knowledge of how acidophilic microorganisms respond to changes in their environment and provide insight into possible gene regulation mechanisms.
The conserved histone chaperone LIN-53 links lifespan and healthspan regulation in Caenorhabditis elegans
Authors: Müthel Stefanie , Uyar Bora , He Mei , Krause Anne , Vitrinel Burcu , Bulut Selman , Vasiljevic Djordje , Akalin Altuna , Kempa Stefan , Tursun Baris 
Published: February 2019

SummaryWhether extension of lifespan provides an extended time without health deteriorations is an important issue for human aging. However, to which degree lifespan and healthspan regulation might be linked is not well understood. Chromatin factors could be involved in linking both aging aspects, as epigenetic mechanisms bridge regulation of different biological processes. The epigenetic factor LIN-53 (RBBP4/7) is required for safeguarding cell identities in Caenorhabditis elegans as well as mammals and for preventing memory loss and premature aging in humans. LIN-53 is a histone chaperone that associates with different chromatin-regulating complexes. We show that LIN-53 interacts with the Nucleosome remodeling and deacteylase (NuRD)-complex in C. elegans muscles to promote healthy locomotion during aging. While mutants for other NuRD members show a normal lifespan, animals lacking LIN-53 die early because LIN-53 depletion affects also the Histone deacetylase complex Sin3, which is required for a normal lifespan. To determine why lin-53 and sin-3 mutants die early, we performed transcriptome and metabolome analysis and found that levels of the disaccharide Trehalose are significantly decreased in both mutants. As Trehalose is required for normal lifespan in C. elegans, lin-53 and sin-3 mutants could be rescued by either feeding with Trehalose or increasing Trehalose levels via the Insulin/IGF1 signaling pathway. Overall, our findings suggest that LIN-53 is required for maintaining lifespan and promoting healthspan through discrete chromatin regulatory mechanisms. Since both LIN-53 and its mammalian homologs safeguard cell identities, it is conceivable that its implication in lifespan and healthspan regulation is also evolutionarily conserved.
Case report of cutaneous nodule caused by Gordonia bronchialis in an immunocompetent patient after receiving acupuncture
Authors: Choi Myoung Eun , Jung Chang Jin , Won Chong Hyun , Chang Sung Eun , Lee Mi Woo , Choi Jee Ho , Lee Woo Jin 
Published: February 2019

AbstractGordonia species were recently found to cause human infection. Most Gordonia bronchialis infections are associated with sternal wounds and foreign bodies. Here, we present a case of a firm cutaneous nodule caused by G. bronchialis on an immunocompetent patient's lower extremity after receiving acupuncture. Our present case indicates that spontaneous cutaneous infection of G. bronchialis can develop even in a healthy patient. With the popularity of complementary and alternative medicine, physicians should be aware that G. bronchialis infection can be associated with Oriental medicine similar to mycobacterial infection. Recognizing the diverse clinical features of newly emerging Gordonia species will facilitate appropriate diagnosis and management of future patients.
Reproductive losses due to climate change‐induced earlier flowering are not the primary threat to plant population viability in a perennial herb
Authors: Iler Amy M. , Compagnoni Aldo , Inouye David W. , Williams Jennifer L. , CaraDonna Paul J. , Anderson Aaron , Miller Tom E. X. 
Published: February 2019

Abstract

Despite a global footprint of shifts in flowering phenology in response to climate change, the reproductive consequences of these shifts are poorly understood. Furthermore, it is unknown whether altered flowering times affect plant population viability.

We examine whether climate change‐induced earlier flowering has consequences for population persistence by incorporating reproductive losses from frost damage (a risk of early flowering) into population models of a subalpine sunflower (Helianthella quinquenervis). Using long‐term demographic data for three populations that span the species’ elevation range (8–15 years, depending on the population), we first examine how snowmelt date affects plant vital rates. To verify vital rate responses to snowmelt date experimentally, we manipulate snowmelt date with a snow removal experiment at one population. Finally, we construct stochastic population projection models and Life Table Response Experiments for each population.

We find that populations decline (λs < 1) as snowmelt dates become earlier. Frost damage to flower buds, a consequence of climate change‐induced earlier flowering, does not contribute strongly to population declines. Instead, we find evidence that negative effects on survival, likely due to increased drought risk during longer growing seasons, drive projected population declines under earlier snowmelt dates.

Synthesis. Shifts in flowering phenology are a conspicuous and important aspect of biological responses to climate change, but here we show that the phenology of reproductive events can be unreliable measures of threats to population persistence, even when earlier flowering is associated with substantial reproductive losses. Evidence for shifts in reproductive phenology, along with scarcer evidence that these shifts actually influence reproductive success, are valuable but can paint an incomplete and even misleading picture of plant population responses to climate change.
Re‐structuring the negotiated order of the hospital
Authors: Nugus Peter 
Published: February 2019

AbstractResearchers continue to lament the lack of organisational focus in the sociology of health and illness. Although studies have increasingly focused on boundaries between organizations, little such research has focused on the formal boundaries within the hospital itself. Given its dramatic compartmentalisation, and continuing prevalence in health systems, the lack of organisational perspective in hospital research limits insights into the effects (as well as the construction) of the order of health work and care. With a greater emphasis on ‘ordering’ in the concept of negotiated order, the aim of this study is to examine the manifestation and consequences of the formal boundaries of hospital departments. Fieldwork featured 12 months of ethnography, including formal and informal observations, 80 audio‐recorded, semi‐structured interviews, and 56 field interviews, in the Emergency Departments (EDs) of two tertiary referral hospitals. Compared with in‐patient hospital departments, the ED has limited legitimacy claims of organ‐specific knowledge to transfer patients out of the ED. The manifestation of specialised knowledge hierarchies in organisational structures disadvantages patients who are older and who have chronic conditions, underpinning the argument that effects as well as the negotiation of stable organisational orders deserve increased attention in the sociology of health and illness.
Take‐home naloxone and the politics of care
Authors: Farrugia Adrian , Fraser Suzanne , Dwyer Robyn , Fomiatti Renae , Neale Joanne , Dietze Paul , Strang John 
Published: February 2019

Abstract‘Take‐home naloxone’ refers to a life‐saving intervention in which a drug (naloxone) is made available to nonmedically trained people for administration to other people experiencing an opioid overdose. In Australia, it has not been taken up as widely as would be expected, given its life‐saving potential. We consider the actions of take‐home naloxone, focusing on how care relations shape its uses and effects. Mobilising Science and Technology Studies insights, we suggest that the uses and effects of naloxone are co‐produced within social relations and, therefore, this initiative ‘affords’ multiple outcomes. We argue that these affordances are shaped by a politics of care, and that these politics relate to uptake. We analyse two complementary case studies, drawn from an interview‐based project, in which opioid consumers discussed take‐home naloxone and its uses. Our analysis maps the ways take‐home naloxone can afford (i) a regime of care within an intimate partnership (allowing a terminally ill man to more safely consume opioids) and (ii) a political process of care (in which a consumer takes care of others treated with the medication by administering it ‘gently’). We conclude by exploring the political affordances of a politics of care approach for the uptake of take‐home naloxone.
Identification of stable senescence‐associated reference genes
Authors: Hernandez‐Segura Alejandra , Rubingh Richard , Demaria Marco 
Published: February 2019

AbstractCellular senescence is a state of permanent cell cycle arrest activated in response to damaging stimuli. Many hallmarks associated with senescent cells are measured by quantitative real‐time PCR (qPCR). As the selection of stable reference genes for interpretation of qPCR data is often overlooked, we performed a systematic review to understand normalization strategies entailed in experiments involving senescent cells. We found that, in violation of the Minimum Information for publication of qPCR Experiments (MIQE) guidelines, most reports used only one reference gene to normalize qPCR data, and that stability of the reference genes was either not tested or not reported. To identify new and more stable reference genes in senescent fibroblasts, we analyzed the Shapiro–Wilk normality test and the coefficient of variation per gene using in public RNAseq datasets. We then compared the new reference gene candidates with commonly used ones by using both RNAseq and qPCR data. Finally, we defined the best reference genes to be used universally or in a strain‐dependent manner. This study intends to raise awareness of the instability of classical reference genes in senescent cells and to serve as a first attempt to define guidelines for the selection of more reliable normalization methods.
Research reported in the AJA: Who does it and where do they do it?
Authors: Howe Anna , Jeon Yun‐Hee 
Published: February 2019

ObjectiveTo review research published in the AJA in terms of authors' positions and disciplinary backgrounds, and the settings in which research was done.MethodsEighty two papers by 373 authors, in Vol. 35 No 1, March 2016, to Vol 37 No 2, June 2018, were reviewed.ResultsDifferent clusters of authorship were found for research using surveys or database analyses, research in hospitals and aged care settings. Two out of three authors held academic positions, and professional practitioners in hospitals were much more likely to have academic affiliations than in aged care settings. Differing research cultures are seen to contribute to these outcomes.ConclusionsEditorial policies have been central to maintaining publication standards. The Journal's publication partners could take a number of actions to advance recognition of professionals in different roles as authors and to expand the range of research published, especially nursing and social science research.
TMEM16A is implicated in the regulation of coronary flow and is altered in hypertension
Authors: Askew Page Henry R. , Dalsgaard Thomas , Baldwin Samuel N. , Jepps Thomas A. , Povstyan Oleksandr , Olesen Søren P. , Greenwood Iain A. 
Published: February 2019

Background and PurposeCoronary artery disease leads to ischaemic heart disease and ultimately myocardial infarction. Thus, it is important to determine the factors that regulate coronary blood flow. Ca2+‐activated chloride channels contribute to the regulation of arterial tone; however, their role in coronary arteries is unknown. The aim of this study was to investigate the expression and function of the main molecular correlate of Ca2+‐activated chloride channels, TMEM16A, in rat coronary arteries.Experimental ApproachWe performed mRNA and protein analysis, electrophysiological studies of coronary artery myocytes, and functional studies of coronary artery contractility and coronary perfusion, using novel inhibitors of TMEM16A. Furthermore, we assessed whether any changes in expression and function occurred in coronary arteries from spontaneously hypertensive rats (SHRs).Key ResultsTMEM16A was expressed in rat coronary arteries. The TMEM16A‐specific inhibitor, MONNA, hyperpolarised the membrane potential in U46619. MONNA, T16Ainh‐A01, and Ani9 attenuated 5‐HT/U46619‐induced contractions. MONNA and T16Ainh‐A01 also increased coronary flow in Langendorff perfused rat heart preparations. TMEM16A mRNA was increased in coronary artery smooth muscle cells from SHRs, and U46619 and 5‐HT were more potent in arteries from SHRs than in those from normal Wistar rats. MONNA diminished this increased sensitivity to U46619 and 5‐HT.Conclusions and ImplicationsIn conclusion, TMEM16A is a key regulator of coronary blood flow and is implicated in the altered contractility of coronary arteries from SHRs.