bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potassium channels contribute to activity-dependent scaling of dendritic inhibition
Authors: Chang Jeremy T. , Higley Michael J. 
Published: January 2017

AbstractGABAergic inhibition plays a critical role in the regulation of neuronal activity. In the neocortex, inhibitory interneurons that target the dendrites of pyramidal cells influence both electrical and biochemical postsynaptic signaling. Voltage-gated ion channels strongly shape dendritic excitability and the integration of excitatory inputs, but their contribution to GABAergic signaling is less well understood. By combining 2-photon calcium imaging and focal GABA uncaging, we show that voltage-gated potassium channels normally suppress the GABAergic inhibition of calcium signals evoked by back-propagating action potentials in dendritic spines and shafts of cortical pyramidal neurons. Moreover, the voltage-dependent inactivation of these channels leads to enhancement of dendritic calcium inhibition following somatic spiking. Computational modeling reveals that the enhancement of calcium inhibition involves an increase in action potential depolarization coupled with the nonlinear relationship between membrane voltage and calcium channel activation. Overall, our findings highlight the interaction between intrinsic and synaptic properties and reveal a novel mechanism for the activity-dependent scaling of GABAergic inhibition.Significance StatementGABAergic inhibition potently regulates neuronal activity in the neocortex. How such inhibition interacts with the intrinsic electrophysiological properties of single neurons is not well-understood. Here we investigate the ability of voltage-gated potassium channels to regulate the impact of GABAergic inhibition in the dendrites of neocortical pyramidal neurons. Our results show that potassium channels normally reduce inhibition directed towards pyramidal neuron dendrites. However, these channels are inactivated by strong neuronal activity, leading to an enhancement of GABAergic potency and limiting the corresponding influx of dendritic calcium. Our findings illustrate a previously unappreciated relationship between neuronal excitability and GABAergic inhibition.
A Comparison of mRNA Sequencing with Random Primed and 3’-Directed Libraries
Authors: Xiong Yuguang , Soumillon Magali , Wu Jie , Hansen Jens , Hu Bin , van Hasselt Johan G.C. , Jayaraman Gomathi , Lim Ryan , Bouhaddou Mehdi , Ornelas Loren , Bochicchio Jim , Lenaeus Lindsay , Stocksdale Jennifer , Shim Jaehee , Gomez Emilda , Sareen Dhruv , Svendsen Clive , Thompson Leslie M. , Mahajan Milind , Iyengar Ravi , Sobie Eric A. , Azeloglu Evren U. , Birtwistle Marc R. 
Published: January 2017

AbstractDeep mRNA sequencing (mRNAseq) is the state-of-the-art for whole transcriptome measurements. A key step is creating a library of cDNA sequencing fragments from RNA. This is generally done by random priming, creating multiple sequencing fragments along the length of each transcript. A 3’ end-focused library approach cannot detect differential splicing, but has potentially higher throughput at lower cost (~10-fold lower), along with the ability to improve quantification by using transcript molecule counting with unique molecular identifiers (UMI) to correct for PCR bias. Here, we compare implementation of such a 3’-digital gene expression (3’-DGE) approach with “conventional” random primed mRNAseq, which has not yet been done. We find that while conventional mRNAseq detects ~15% more genes, the resulting lists of differentially expressed genes and therefore biological conclusions and gene signatures are highly concordant between the two techniques. We also find good quantitative agreement on the level of individual genes between the two techniques in terms of both read counts and fold change between two conditions. We conclude that for high-throughput applications, the potential cost savings associated with the 3’-DGE approach are a very reasonable tradeoff for modest reduction in sensitivity and inability to observe alternative splicing, and should enable much larger scale studies focused on not only differential expression analysis, but also quantitative transcriptome profiling. The computational scripts and programs, along with experimental standard operating procedures used in our pipeline presented here, are freely available on our website (www.dtoxs.org).
The demographic and adaptive history of the African green monkey
Authors: Pfeifer Susanne P. 
Published: January 2017

AbstractRelatively little is known about the evolutionary history of the African green monkey (genusChlorocebus) due to the lack of sampled polymorphism data from wild populations. Yet, this characterization of genetic diversity is not only critical for a better understanding of their own history, but also for human biomedical research given that they are one of the most widely used primate models. Here, I analyze the demographic and selective history of the African green monkey, utilizing one of the most comprehensive catalogs of wild genetic diversity to date, consisting of 1,795,643 autosomal single nucleotide polymorphisms in 25 individuals, representing all five major populations:C. a. aethiops,C. a. cynosurus,C. a. pygerythrus,C. a. sabaeus, andC. a tantalus. Assuming a mutation rate of 5.9 × 10−9per base pair per generation and a generation time of 8.5 years, divergence time estimates range from 523-621kya for the basal split ofC. a. aethiopsfrom the other four populations. Importantly, the resulting tree characterizing the relationship and split-times between these populations differs significantly from that presented in the original genome paper, owing to their neglect of within-population variation when calculating between population-divergence. In addition, I find that the demographic history of all five populations is well explained by a model of population fragmentation and isolation, rather than novel colonization events. Finally, utilizing these demographic models as a null, I investigate the selective history of the populations, identifying candidate regions potentially related to adaptation in response to pathogen exposure.
Distinguishing Mechanisms Underlying EMT Tristability
Authors: Jia Dongya , Jolly Mohit Kumar , Tripathi Satyendra C. , Hollander Petra Den , Huang Bin , Lu Mingyang , Celiktas Muge , Ramirez-Peña Esmeralda , Ben-Jacob Eshel , Onuchic José N. , Hanash Samir M. , Mani Sendurai A. , Levine Herbert 
Published: January 2017

AbstractBackground:The Epithelial-Mesenchymal Transition (EMT) endows epithelial-looking cells with enhanced migratory ability during embryonic development and tissue repair. EMT can also be co-opted by cancer cells to acquire metastatic potential and drug-resistance. Recent research has argued that epithelial (E) cells can undergo either a partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype that typically displays collective migration, or a complete EMT to adopt a mesenchymal (M) phenotype that shows individual migration. The core EMT regulatory network - miR-34/SNAIL/miR-200/ZEB1 - has been identified by various studies, but how this network regulates the transitions among the E, E/M, and M phenotypes remains controversial. Two major mathematical models – ternary chimera switch (TCS) and cascading bistable switches (CBS) - that both focus on the miR-34/SNAIL/miR-200/ZEB1 network, have been proposed to elucidate the EMT dynamics, but a detailed analysis of how well either or both of these two models can capture recent experimental observations about EMT dynamics remains to be done.Results:Here, via an integrated experimental and theoretical approach, we first show that both these two models can be used to understand the two-step transition of EMT - E→E/M→M, the different responses of SNAIL and ZEB1 to exogenous TGF-β and the irreversibility of complete EMT. Next, we present new experimental results that tend to discriminate between these two models. We show that ZEB1 is present at intermediate levels in the hybrid E/M H1975 cells, and that in HMLE cells, overexpression of SNAIL is not sufficient to initiate EMT in the absence of ZEB1 and FOXC2.Conclusions:These experimental results argue in favor of the TCS model proposing that miR-200/ZEB1 behaves as a three-way decision-making switch enabling transitions among the E, hybrid E/M and M phenotypes.
Effect of a selective SGLT2 inhibitor, luseogliflozin, on circadian rhythm of sympathetic nervous function and locomotor activities in metabolic syndrome rats
Authors: Rahman Asadur , Fujisawa Yoshihide , Nakano Daisuke , Hitomi Hirofumi , Nishiyama Akira 
Published: January 2017

SummaryMetabolic syndrome is often associated with disruption of circadian rhythm of systemic haemodynamics and cardiovascular disease. Experiments were conducted to investigate the effects of luseogliflozin, a selective SGLT2 inhibitor, on circadian rhythm of sympathetic nervous function and locomotor activity (LA) in metabolic syndrome rats. The difference in the low frequency component of systolic blood pressure between the dark and light period significantly increased in the luseogliflozin‐treated SHRcp. LA also increased in the dark period compared with the light period following luseogliflozin treatment. These data suggest that circadian rhythm of sympathetic nervous function and LA is improved by luseogliflozin in metabolic syndrome rats, which may contribute to SGLT2 inhibitor‐induced improvement of cardiovascular outcomes.
Soil microbial communities are shaped by vegetation type and park age in cities under cold climate
Authors: Hui Nan , Jumpponen Ari , Francini Gaia , Kotze D. Johan , Liu Xinxin , Romantschuk Martin , Strömmer Rauni , Setälä Heikki 
Published: January 2017

SummarySoil microbes play a key role in controlling ecosystem functions and providing ecosystem services. Yet, microbial communities in urban green space soils remain poorly characterized. Here we compared soil microbial communities in 41 urban parks of (i) divergent plant functional types (evergreen trees, deciduous trees and lawn) and (ii) different ages (constructed 10, ∼50 and >100 years ago). These microbial communities were also compared to those in 5 control forests in southern Finland. Our results indicate that, despite frequent disturbances in urban parks, urban soil microbes still followed the classic patterns typical of plant‐microbe associations in natural environments: both bacterial and fungal communities in urban parks responded to plant functional groups, but fungi were under tighter control of plants than bacteria. We show that park age shaped the composition of microbial communities, possibly because vegetation in old parks have had a longer time to modify soil properties and microbial communities than in young parks. Furthermore, control forests harboured distinct but less diverse soil microbial communities than urban parks that are under continuous anthropogenic disturbance. Our results highlight the importance of maintaining a diverse portfolio of urban green spaces and plant communities therein to facilitate complex microbial communities and functions in urban systems.
Biogeochemical spatio‐temporal transformation of copper in Aspergillus niger colonies grown on malachite with different inorganic nitrogen sources
Authors: Fomina Marina , Bowen Andrew D. , Charnock John M. , Podgorsky Valentin S. , Gadd Geoffrey M. 
Published: January 2017

SummaryThis work elucidates spatio‐temporal aspects of the biogeochemical transformation of copper mobilized from malachite (Cu2(CO3)(OH)2) and bioaccumulated within Aspergillus niger colonies when grown on different inorganic nitrogen sources. It was shown that the use of either ammonium or nitrate determined how copper was distributed within the colony and its microenvironment and the copper oxidation state and succession of copper coordinating ligands within the biomass. Nitrate‐grown colonies yielded ∼1.7× more biomass, bioaccumulated ∼7× less copper, excreted ∼1.9× more oxalate and produced ∼1.75× less water‐soluble copper in the medium in contrast to ammonium‐grown colonies. Microfocus X‐ray absorption spectroscopy revealed that as the mycelium matured, bioaccumulated copper was transformed from less stable and more toxic Cu(I) into less toxic Cu(II) which was coordinated predominantly by phosphate/malate ligands. With time, a shift to oxalate coordination of bioaccumulated copper occurred in the central older region of ammonium‐grown colonies.
Symbiotic bacteria associated with a bobtail squid reproductive system are detectable in the environment, and stable in the host and developing eggs
Authors: Kerwin Allison H. , Nyholm Spencer V. 
Published: January 2017

SummaryFemale Hawaiian bobtail squid, Euprymna scolopes, have an accessory nidamental gland (ANG) housing a bacterial consortium that is hypothesized to be environmentally transmitted and to function in the protection of eggs from fouling and infection. The composition, stability, and variability of the ANG and egg jelly coat (JC) communities were characterized and compared to the bacterial community composition of the surrounding environment using Illumina sequencing and transmission electron microscopy. The ANG bacterial community was conserved throughout hosts collected from the wild and was not affected by maintaining animals in the laboratory. The core symbiotic community was composed of Alphaproteobacteria and Opitutae (a class of Verrucomicrobia). Operational taxonomic units representing 94.5% of the average ANG abundance were found in either the seawater or sediment, which is consistent with the hypothesis of environmental transmission between generations. The bacterial composition of the JC was stable during development and mirrored that of the ANG. Bacterial communities from individual egg clutches also grouped with the ANG of the female that produced them. Collectively, these data suggest a conserved role of the ANG/JC community in host reproduction. Future directions will focus on determining the function of this symbiotic community, and how it may change during ANG development.
Health Risk Factors Associated with Lifetime Abstinence from Alcohol in the 1979 National Longitudinal Survey of Youth Cohort
Authors: Kerr William C. , Lui Camillia K. , Williams Edwina , Ye Yu , Greenfield Thomas K. , Lown E. Anne 
Published: January 2017

BackgroundThe choice and definition of a comparison group in alcohol‐related health studies remains a prominent issue in alcohol epidemiology due to potential biases in the risk estimates. The most commonly used comparison group has been current abstainers; however, this includes former drinkers who may have quit drinking due to health problems. Lifetime abstention could be the best option, but measurement issues, selection biases due to health and other risk factors, and small numbers in populations are important concerns. This study examines characteristics of lifetime abstention and occasional drinking that are relevant for alcohol‐related health studies.MethodsThis study used data from the National Longitudinal Survey of Youth 1979 cohort of 14 to 21 year olds followed through 2012 (n = 7,515). Definitions of abstinence and occasional drinking were constructed based on multiple measurements. Descriptive analyses were used to compare the definitions, and in further analysis, lifetime abstainers (n = 718) and lifetime minimal drinkers (n = 1,027) were compared with drinkers across demographics and early‐life characteristics (i.e., religion, poverty, parental education, and family alcohol problems) in logistic regression models.ResultsUsing a strict measurement of zero drinks from adolescence to the 50s, only 1.7% of the sample was defined as lifetime abstainer compared to a broader definition allowing a total of 1 drink over the lifetime that included 9.5% and to lifetime minimal drinking (a total of 3 drinks or less a month), which accounted for 13.7%. Factors significantly associated with lifetime abstention and lifetime minimal drinking included religion, poverty, having no family alcohol problems, Hispanic ethnicity, foreign‐born, and female gender. Importantly, work‐related health limitations in early life were significantly associated, but not childhood physical and mental health problems.ConclusionsAlcohol‐related health studies should utilize lifetime classifications of drinkers and abstainers, and, in doing so, should account for early‐life socioeconomic adversity and childhood health factors or consider these as unmeasured confounders.
Perivascular adipose tissue inflammation in vascular disease
Authors: Nosalski Ryszard , Guzik Tomasz J 
Published: January 2017

Perivascular adipose tissue (PVAT) plays a critical role in the pathogenesis of cardiovascular disease. In vascular pathologies, perivascular adipose tissue increases in volume and becomes dysfunctional, with altered cellular composition and molecular characteristics. PVAT dysfunction is characterized by its inflammatory character, oxidative stress, diminished production of vaso‐protective adipocyte‐derived relaxing factors and increased production of paracrine factors such as resistin, leptin, cytokines (IL‐6 and TNF‐α) and chemokines [RANTES (CCL5) and MCP‐1 (CCL2)]. These adipocyte‐derived factors initiate and orchestrate inflammatory cell infiltration including primarily T cells, macrophages, dendritic cells, B cells and NK cells. Protective factors such as adiponectin can reduce NADPH oxidase superoxide production and increase NO bioavailability in the vessel wall, while inflammation (e.g. IFN‐γ or IL‐17) induces vascular oxidases and eNOS dysfunction in the endothelium, vascular smooth muscle cells and adventitial fibroblasts. All of these events link the dysfunctional perivascular fat to vascular dysfunction. These mechanisms are important in the context of a number of cardiovascular disorders including atherosclerosis, hypertension, diabetes and obesity. Inflammatory changes in PVAT's molecular and cellular responses are uniquely different from classical visceral or subcutaneous adipose tissue or from adventitia, emphasizing the unique structural and functional features of this adipose tissue compartment. Therefore, it is essential to develop techniques for monitoring the characteristics of PVAT and assessing its inflammation. This will lead to a better understanding of the early stages of vascular pathologies and the development of new therapeutic strategies focusing on perivascular adipose tissue.Linked ArticlesThis article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue – Potential Pharmacological Targets? To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc
Elevated semaphorin5A in systemic lupus erythematosus is in association with disease activity and lupus nephritis
Authors: Du Y , Wu X , Chen M , Wang W , Xv W , Ye L , Wu D , Xue J , Sun W , Luo J , Wu H 
Published: January 2017

Summary
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by extensive immune response, including over-activation of T and B cell development of pathogenic autoantibodies, organ damage induced by the formation and deposition of immune complex and the abnormal elevation of type I interferon. Semaphorin5A (Sema5A) is involved essentially in immune cell regulation and is also implicated in the pathogenesis of autoimmune disorders. We aimed to evaluate the role of Sema5A in patients with SLE. Serum levels of Sema5A were tested by enzyme-linked immunosorbent assay (ELISA) in 152 SLE patients and 48 healthy controls. The message ribonucleic acid (mRNA) expression levels of Sema5A and ADAM metallopeptidase domain 17 (ADAM17) in the peripheral blood mononuclear cells (PBMC) from 43 patients with SLE and 19 healthy controls were detected by the real-time–quantitative polymerase chain reaction (qPCR). Serum Sema5A levels were increased significantly in SLE patients compared with healthy controls (P &lt; 0·001). Elevated levels of Sema5A were correlated positively with 24-h proteinuria excretion (r = 0·558, P &lt; 0·0001), SLE disease activity index (SLEDAI) (r = 0·278, P = 0·0006) and C-reactive protein (CRP) (r = 0·266, P = 0·002), but negatively with planet (PLT) (r = –0·294, P = 0·0003) and complement 3 (C3) (r = –0·287, P = 0·0004) in SLE patients. Patients with elevated Sema5A levels showed higher incidence of rash, serositis and nephritis (P &lt; 0·05 or P &lt; 0·001). Patients with decreased PLT, C3 or positive for proteinuria also showed elevated Sema5A (P &lt; 0·001 or P &lt; 0·05). The mRNA ADAM17 was increased in SLE patients and correlated positively with serum Sema5A levels. Our data demonstrated that elevated serum Sema5A in SLE patients correlated with disease activity and are involved in kidney and blood system damage; ADAM17 might be involved in the release of secreted Sema5A.
Single‐sided deafness affects language and auditory development – a case–control study
Authors: Sangen A. , Royackers L. , Desloovere C. , Wouters J. , van Wieringen A. 
Published: January 2017

ObjectivesTo examine auditory, linguistic and cognitive outcomes of children with single‐sided deafness (SSD). An increasing body of research suggests that children with SSD lag behind with respect to their normal hearing (NH) peers. In this study, we tap into certain developmental skills.DesignCase–control study.ParticipantsTwenty‐one children with SSD between 5 and 15 years of age participated. Per child with SSD, two NH control children were matched on age and gender.Outcome measuresMorphology, syntax and vocabulary were examined, and performance was assessed in depth by focusing on subskills and type of errors made. Furthermore, tests of short‐term and working memory were conducted, and aspects of hearing disability were assessed by means of the speech spatial and qualities of hearing questionnaire (SSQ).Main resultsThe children with SSD lagged behind in their scores on the three language tests and showed some differences to the NH group concerning type of errors and difficulty of the several subskills. Furthermore, scores on the SSQ indicated that in daily life, the children with SSD experience problems in spatial hearing and in understanding speech in noisy situations and that the effort they have to put into listening and in understanding speech is considerably greater than in NH children.ConclusionsThis study showed differences between children with SSD and NH children on several language skills and on auditory behaviour. Possibly, early intervention could prevent such language difficulties and minimise problems with spatial hearing and speech understanding.