bluuebunny/crossref_metadata_2025_split huggingface dataset:
Congruency effects can compensate for deficits of healthy older adults in crossmodal integration
Authors: Higgen Focko L. , Heine Charlotte , Krawinkel Lutz , Göschl Florian , Engel Andreas K. , Hummel Friedhelm C. , Xue Gui , Gerloff Christian 
Published: June 2019

AbstractOne of the pivotal challenges of aging is to maintain independence in the activities of daily life. In order to adapt to changes in the environment, it is crucial to continuously process and accurately combine simultaneous input from different sensory systems, i.e., crossmodal integration.With aging, performance decreases in multiple cognitive domains. The processing of sensory stimuli constitutes one of the key features of this deterioration. Age-related sensory impairments affect all modalities, substantiated by decreased acuity in visual, auditory or tactile detection tasks.However, whether this decline of sensory processing leads to impairments in crossmodal integration remains an unresolved question. While some researchers propose that crossmodal integration degrades with age, others suggest that it is conserved or even gains compensatory importance.To address this question, we compared behavioral performance of older and young participants in a well-established crossmodal matching task, requiring the evaluation of congruency in simultaneously presented visual and tactile patterns. Older participants performed significantly worse than young controls in the crossmodal task when being stimulated at their individual unimodal visual and tactile perception thresholds. Performance increased with adjustment of stimulus intensities. This improvement was driven by better detection of congruent stimulus pairs (p<0.01), while detection of incongruent pairs was not significantly enhanced (p=0.12).These results indicate that age-related impairments lead to poor performance in complex crossmodal scenarios and demanding cognitive tasks. Performance is enhanced when inputs to the visual and tactile systems are congruent. Congruency effects might therefore be used to develop strategies for cognitive training and neurological rehabilitation.
Gene expression profiling ofcorpus luteumreveals the importance of immune system during early pregnancy in domestic sheep
Authors: Pokharel Kisun , Peippo Jaana , Weldenegodguad Melak , Honkatukia Mervi , Li Meng-Hua , Kantanen Juha 
Published: June 2019

AbstractThe majority of pregnancy loss in ruminants occurs during the preimplantation stage, which is thus the most critical period determining reproductive success. While ovulation rate is the major determinant of litter size in sheep, interactions among the conceptus,corpus luteumand endometrium are essential for pregnancy success. Here, we performed a comparative transcriptome study by sequencing total mRNA from corpus luteum (CL) collected during the preimplantation stage of pregnancy in Finnsheep, Texel and F1 crosses, and mapping the RNA-Seq reads to the latest Rambouillet reference genome. A total of 21,287 genes were expressed in our dataset. Highly expressed autosomal genes in the CL were associated with biological processes such as progesterone formation (STAR, CYP11A1, andHSD3B1) and embryo implantation (eg.TIMP1, TIMP2andTCTP). Among the list of differentially expressed genes, a group of sialic acid-binding immunoglobulin (Ig)-like lectins (Siglecs), solute carriers (SLC13A5, SLC15A2, SLC44A5) and chemokines (CCL5, CXCL13, CXCL9) were upregulated in Finnsheep, while four multidrug resistance-associated proteins (MRPs) were upregulated in Texel ewes. A total of 17 genes and two non-coding RNAs (ncRNA) were differentially expressed in breed-wise comparisons owing to flushing diet effect. Moreover, we report, for the first time in any species, several genes that are active in the CL during early pregnancy (includingSIGLEC13, SIGLEC14, SIGLEC6, MRP4, andCA5A). Importantly, functional analysis of differentially expressed genes suggested that Finnsheep have a better immune system than Texel and that high prolificacy in Finnsheep might be governed by immune system regulation.
Uniquely excitable neurons enable precise and persistent information transmission through the retrosplenial cortex
Authors: Brennan Ellen K.W. , Sudhakar Shyam Kumar , Jedrasiak-Cape Izabela , Ahmed Omar J. 
Published: June 2019

ABSTRACTThe retrosplenial cortex (RSC) is essential for both memory and navigation, but the neural codes underlying these functions remain largely unknown. Here, we show that the most prominent cell type in layers 2/3 (L2/3) of the granular RSC is a uniquely excitable, small pyramidal cell. These cells have a low rheobase (LR), high input resistance, lack of spike-frequency adaptation, and spike widths intermediate to those of neighboring fast-spiking (FS) inhibitory neurons and regular-spiking (RS) excitatory neurons. LR cells are excitatory but rarely synapse onto neighboring neurons. Instead, L2/3 of RSC is an inhibition-dominated network with dense connectivity between FS cells and from FS to LR neurons. Biophysical models of LR but not RS cells precisely and continuously encode sustained input from afferent postsubicular head-direction cells. Thus, the unique intrinsic properties of LR neurons can support both the precision and persistence necessary to encode information over multiple timescales in the RSC.
K+ uptake and root-to-shoot allocation in Arabidopsis require coordination of nitrate transporter1/peptide transporter family member NPF6.3/NRT1.1
Authors: Fang Xian Zhi , Liu Xing Xing , Zhu Ya Xing , Ye Jia Yuan , Jin Chong Wei 
Published: June 2019

AbstractK+ and NO3- are the major forms of potassium and nitrogen that are absorbed by the roots of most terrestrial plants. In this study, we observed that the close relationship between NO3- and K+ homeostasis was mediated by nitrate transporter1 (NRT1.1) in Arabidopsis. The nrt1.1 mutants lacking NRT1.1 function showed disturbed K+ uptake and root-to-shoot allocation, especially under K+-limited conditions, and had a yellow-shoot sensitive phenotype on K+-limited medium. The K+ uptake and root-to-shoot allocation of these mutants were partially rescued by expressing NRT1.1 in the root epidermis-cortex and central vasculature by using Sultr1;2 and PHO1 promoters, respectively. Furthermore, two-way analysis of variance based on the K+ content in nrt1.1-1/akt1, nrt1.1-1/hak5-3, nrt1.1-1/kup7, and nrt1.1-1/skor-2 double mutants and their corresponding single mutants and wild-type plants revealed physiological interactions between NRT1.1 and K+ channels located in the root epidermis-cortex and central vasculature. Taken together, these data suggest that the expression of NRT1.1 in the root epidermis-cortex coordinates with K+ uptake channels to improve K+ uptake, whereas its expression in the root central vasculature coordinates with the channels loading K+ into the xylem to facilitate K+ allocation from the roots to the shoot.
Maintenance of fertility in the face of meiotic drive
Authors: Meade Lara , Finnegan Sam , Kad Ridhima , Fowler Kevin , Pomiankowski Andrew 
Published: June 2019

AbstractSelfish genetic elements that gain a transmission advantage through the destruction of sperm have grave implications for drive male fertility. In the X-linked SR meiotic drive system of a stalk-eyed fly, we found that drive males have greatly enlarged testes and maintain high fertility despite the destruction of half their sperm, even when challenged with fertilising large numbers of females. Conversely, we observed reduced allocation of resources to the accessory glands that probably explains the lower mating frequency of SR males. Body size and eyespan were also reduced, which are likely to impair viability and pre-copulatory success. We discuss the potential evolutionary causes of these differences between drive and standard males.
Comprehensive analysis of human microRNA-mRNA interactome
Authors: Plotnikova Olga , Baranova Ancha , Skoblov Mikhail 
Published: June 2019

AbstractMicroRNAs play a key role in the regulation of gene expression. A majority of microRNA-mRNA interactions remain unidentified. Despite extensive research, our ability to predict human microRNA-mRNA interactions using computational algorithms remains limited by a complexity of the models for non-canonical interactions, and an abundance of false positive results.Here we present the landscape of microRNA-mRNA human interactions, which we derived from comprehensive analysis of datasets describing direct microRNA-mRNA interactions experimentally defined in HEK293 and Huh7.5 cell lines, along with other available microRNA and mRNA expression data. We have also established a collection of reliable microRNA binding regions that we systematically extracted in course of analysis of 79 CLIP datasets, which is available at http://score.generesearch.ru/services/mirna/.While only 1-2% of human genes interact with microRNAs, some RNAs display a substantial sponge effect, which is specific to the cell line of study. Some microRNAs are expressed at a very high level, while interacting with only a few mRNAs, thus, indeed, serving as specific gene expression regulators. Other miRNAs might be expressed at relatively low levels, and interact with many mRNAs. Some of the microRNAs might switch between these two classes, depending on cellular context. Results of our study provide an initial resolution into the complex patterns of human microRNA-mRNA interactions.
MKS-NPHP module proteins regulate ciliary shedding inParamecium
Authors: Gogendeau Delphine , Lemullois Michel , Aubusson-Fleury Anne , Arnaiz Olivier , Cohen Jean , Vesque Christine , Schneider-Maunoury Sylvie , Koll France , Tassin Anne-Marie 
Published: June 2019

ABSTRACTCiliogenesis is a general process in eukaryotic cells and its different steps begin to be well characterised. However, the molecular mechanisms leading to decilation or ciliary shedding are still poorly understood. This process, observed from unicellular organisms such asChlamydomonasorParameciumto multiciliated cells from trachea or fallopian tube of vertebrates, seems to be a general process since recent observations demonstrates its requirement during the cell cycle or neurogenesis. Interestingly, in all cellular models, ciliary shedding occurs distal to the transition zone, essentially known to act as a diffusion barrier between the intracellular space and the cilium, suggesting conserved molecular mechanisms.To determine if MKS and NPHP modules, known to cooperate to establish transition zone formation and function, could control ciliary shedding, we studied inParameciumthe function of TMEM216/MKS2 and TMEM107 (two members of the MKS module), NPHP4 (one member of the NPHP module), CEP290/NPHP6 and RPGRIP1L/MKS5. We show that all these proteins are recruited to the TZ as soon as growing cilia are detected and localise with a 9-fold symmetry at the level of the axonemal plate. Interestingly, we demonstrate that the depletion of the two MKS module proteins induces spontaneous cilia shedding, while the depletion of either NPHP4, CEP290 or RPGRIP1L inhibits the process. Our results constitute the first evidence for a role of conserved TZ proteins in deciliation and open new directions for understanding motile cilia physiology.
Tbx2amodulates switching of opsin gene expression
Authors: Sandkam Benjamin A , Campello Laura , O’Brien Conor , Nandamuri Sri Pratima , Gammerdinger William , Conte Matthew , Swaroop Anand , Carleton Karen L 
Published: June 2019

ABSTRACTDifferences in sensory tuning are reported to maintain species boundaries and may even lead to speciation. Variation in the tuning of color vision is likely due to differences in the expression of opsin genes. Over 1,000 species of African cichlid fishes provide an excellent model system for studying the genetic basis of opsin gene expression because of the presence of seven distinct genes, yet individual species typically express only a divergent set of three opsins. The evolution of such shifts is expected to arise through either (a) two simultaneous regulatory changes (one for each opsin), or (b) one regulatory change that simultaneously promotes expression of one opsin while repressing another. Here, we used QTL analyses, genome sequencing, and gene expression studies to identify the transcription factor Tbx2a as likely driving a switch betweenLWSandRH2opsin expression. Binding sites for Tbx2a in theLWSpromoter and the highly conserved Locus Control Region ofRH2act to concurrently promoteLWSexpression while repressingRH2expression. Our data support the hypothesis that instant changes in visual tuning can be achieved by switching the expression of multiple genes by a single mutation and do not require independent changes in the regulatory regions of each opsin.
Hydrogen exchange of chemoreceptors in functional complexes suggests protein stabilization mediates long-range allosteric coupling
Authors: Li Xuni , Eyles Stephen J. , Thompson Lynmarie K. 
Published: June 2019

ABSTRACTBacterial chemotaxis receptors form extended hexagonal arrays that integrate and amplify signals to control swimming behavior. Transmembrane signaling begins with a 2 Å ligand-induced displacement of an alpha helix in the periplasmic and transmembrane domains, but it is not known how the cytoplasmic domain propagates the signal an additional 200 Å to control the kinase CheA bound to the membrane-distal tip of the receptor. The receptor cytoplasmic domain has previously been shown to be highly dynamic as both a cytoplasmic fragment (CF) and within the intact chemoreceptor; modulation of its dynamics are thought to play a key role in signal propagation. Hydrogen deuterium exchange mass spectrometry (HDX-MS) of functional complexes of CF, CheA, and CheW bound to vesicles in native-like arrays reveals that the CF is well-ordered only in its protein interaction region where it binds CheA and CheW. Rapid exchange is observed throughout the rest of the CF, with both uncorrelated (EX2) and correlated (EX1) exchange patterns, suggesting the receptor cytoplasmic domain retains disorder even within functional complexes. HDX rates are increased by inputs that favor the kinase-off state. We propose that chemoreceptors achieve long-range allosteric control of the kinase through a coupled equilibrium: CheA binding in a kinase-on conformation stabilizes the cytoplasmic domain, and signaling inputs that destabilize this domain (ligand binding and demethylation) disfavor CheA binding such that it loses key contacts and reverts to a kinase-off state. This study reveals the mechanistic role of an intrinsically disordered region of a transmembrane receptor in long-range allostery.
Biophysical Basis of Hb-S Polymerization in Red Blood Cell Sickling
Authors: Li W. 
Published: June 2019

ABSTRACTSickle cell disease (SCD) is an autosomal recessive genetic disease caused by the Glu6Val mutation in the β chain (Hb) of the oxygen-carrying hemoglobin protein in sicklemia patients. In the molecular pathogenesis of SCD, the sickle hemoglobin (Hb-S) polymerization is a major driver for structural deformation of red blood cells, i.e. red blood cell (RBC) sickling. Biophysically, it still remains elusive how this SCD-linked E6V mutation leads to Hb-S polymerization in RBC sickling. Therefore, with a comprehensive set of analysis of experimental Hb structures, this letter highlights electrostatic repulsion as a key biophysical mechanism of Hb-S polymerization in RBC sickling, which provides atomic-level insights into the functional impact of the SCD-linked E6V substitution from a biophysical point of view.SIGNIFICANCEDuring the past 25 years, a total of 104 Hb-related structures have been deposited in PDB. For the first time, this article presents a comprehensive set of electrostatic analysis of the 104 experimental structures, highlighting electrostatic repulsion as a fundamental biophysical mechanism for Hb-S polymerization in RBC sickling. The structural and electrostatic analysis here also provides biophysical insights into the functional impact of the SCD-linked E6V substitution.
Assembly properties of FtsZ from cyanobacteriumSynechocystissp. PCC 6803
Authors: Wang Na , Bian Li , Ma Xueqin , Meng Yufeng , Chen Cyndi S. , Rahman Mujeeb ur , Zhang Tingting , Li Zhe , Wang Ping , Chen Yaodong 
Published: June 2019

ABSTRACTTubulin homologue FtsZ is the major cytoskeletal protein in the bacterial cell division machinery. Here, we studied the biochemical and assembly properties of SyFtsZ, FtsZ from cyanobacteriumSynechocystissp. PCC 6803. SyFtsZ had a slow GTPase activity of around 0.4 GTP per FtsZ per minute and assembled into thick, straight protofilament bundles and curved bundles designated toroids. The assembly of SyFtsZ in the presence of GTP occurred in two stages. The first stage was assembled into single straight protofilaments and opened circles; the second stage was association of the protofilaments into straight protofilament bundles and toroids. In addition to these assemblies in GTP, highly curved oligomers and minirings could be observed after GTP hydrolysis or in the presence of GDP. Those three types of protofilaments of SyFtsZ provide support for the hypothesis for a constriction force based on curved protofilaments.
Pax2a regulates angiogenesis to facilitate mmp2-dependent basement membrane remodeling of the optic fissure
Authors: Weaver Megan L. , Piedade W. P , Meshram N.N , Famulski J.K. 
Published: June 2019

ABSTRACTVertebrate retinal development requires timely and precise fusion of the optic fissure (OF). Recent studies have suggested hyaloid vasculature to be involved in optic fissure fusion. In order to examine this link, we analyzed OF fusion and hyaloid vasculogenesis in the zebrafish pax2anoimutant line. We determined that OF basement membrane (BM) remodeling, normally preceded by F-actin accumulation is mis-regulated in pax2a−/−embryos. Comparing transcriptomic profiles of pax2a−/−and wildtype eyes we discovered a novel connection between regulation of angiogenesis and fusion. Pax2a−/−eyes exhibited a significant reduction oftalin1expression, a regulator of hyaloid vasculature, in addition to increased expression of an anti-angiogenic protease,adamts1. Using 3D and live imaging we observed reduced OF hyaloid vascularization in pax2a−/−embryos. Additionally, pharmacological inhibition of VEGF signaling oradamts1mRNA overexpression phenocopied the pax2a−/−vasculature, F-actin and BM remodeling phenotypes. Finally, we show that hyaloid vasculature expressesmmp2which is necessary for remodeling the fissure BM. Taken together we propose a pax2a driven mechanism that restricts anti-angiogenic activity of adamts1 enabling hyaloid vasculature invasion of the OF and delivery of the BM remodeler mmp2.
Estimation and Validation of Individualized Dynamic Brain Models with Resting State fMRI
Authors: Singh Matthew F. , Braver Todd S. , Cole Michael W. , Ching ShiNung 
Published: June 2019

AbstractA key challenge for neuroscience is to develop generative, causal models of the human nervous system in an individualized, data-driven manner. Previous initiatives have either constructed biologically-plausible models that are not constrained by individual-level human brain activity or used data-driven statistical characterizations of individuals that are not mechanistic. We aim to bridge this gap through the development of a new modeling approach termed Mesoscale Individualized Neurodynamic (MINDy) modeling, wherein we fit nonlinear dynamical systems models directly to human brain imaging data. The MINDy framework is able to produce these data-driven network models for hundreds to thousands of interacting brain regions in just 1-3 minutes per subject. We demonstrate that the models are valid, reliable, and robust. We show that MINDy models are predictive of individualized patterns of resting-state brain dynamical activity. Furthermore, MINDy is better able to uncover the mechanisms underlying individual differences in resting state activity than functional connectivity methods.
PfGCN5, a global regulator of stress responsive genes, modulates artemisinin resistance inPlasmodium falciparum
Authors: Rawat Mukul , Kanyal Abhishek , Sahasrabudhe Aishwarya , Vembar Shruthi S. , Lopez-Rubio Jose-Juan , Karmodiya Krishanpal 
Published: June 2019

AbstractPlasmodium falciparumhas evolved resistance to almost all front-line drugs including artemisinins, which threatens malaria control and elimination strategies. Oxidative stress and protein damage responses have emerged as key players in the generation of artemisinin resistance. In this study, we show that PfGCN5, a histone acetyltransferase, binds to the stress responsive and multi-variant family genes in poised state and regulates their expression under stress conditions. We have also provided biochemical and cellular evidences that PfGCN5 regulates stress responsive genes by acetylation of PfAlba3. Furthermore, we show that upon artemisinin exposure, genome-wide binding sites for PfGCN5 are increased and it is directly associated with the genes implicated in artemisinin resistance generation like BiP and TRiC chaperone. Moreover, inhibition of PfGCN5 in artemisinin resistant parasites, Kelch13 mutant, K13I543T and K13C580Y (RSA∼ 25% and 6%, respectively) reverses the sensitivity of the parasites to artemisinin treatment indicating its role in drug resistance generation. Together, these findings elucidate the role of PfGCN5 as a global chromatin regulator of stress-responses with potential role in modulating artemisinin drug resistance, and identify PfGCN5 as an important target against artemisinin resistant parasites.Author SummaryMalaria parasites are constantly adapting to the drugs we used to eliminate them. Thus, when we use the drugs to kill parasites; with time, we select the parasites with the favourable genetic changes. Parasites develop various strategies to overcome exposure to the drugs by exhibiting the stress responses. The changes specific to the drug adapted parasites can be used to understand the mechanism of drug resistance generation. In this study, we have identified PfGCN5 as a global transcriptional regulator of stress responses inPlasmodium falciparum. Inhibition of PfGCN5 reverses the sensitivity of the parasites to the artemisinin drug and identify PfGCN5 as an important target against artemisinin resistant parasites.
Stress-responsive Entamoeba topoisomerase II: a potential anti-amoebic target
Authors: Varghese Sneha Susan , Ghosh Sudip Kumar 
Published: June 2019

AbstractTopoisomerases are ubiquitous enzymes, involved in all DNA processes across the biological world. These enzymes are also targets for various anticancer and antimicrobial agents. The causative organism of amoebiasis, Entamoeba histolytica (Eh), has seven unexplored genes annotated as putative topoisomerases. One of the seven topoisomerases in this parasite was found to be highly up-regulated during heat shock and oxidative stress. The bioinformatic analysis shows that it is a eukaryotic type IIA topoisomerase. Its ortholog was also highly up-regulated during the late hours of encystation in E. invadens (Ei), the encystation model of Eh. Immunoprecipitated endogenous EhTopoII showed topoisomerase II activity in vitro. Immunolocalization studies show that this enzyme colocalized with newly forming nuclei during encystation, which is a significant event in maturing cysts. Double-stranded RNA mediated down-regulation of the TopoII both in Eh and Ei reduced the viability of actively growing trophozoites and also reduced the encystation efficiency in Ei. Drugs, targeting eukaryotic topoisomerase II, e.g., etoposide, ICRF193, and amsacrine, show 3-5 times higher EC50 in Eh than that of mammalian cells. Sequence comparison with human TopoIIα showed that key amino acid residues involved in the interactions with etoposide and ICRF193 are different in Entamoeba TopoII. Interestingly, ciprofloxacin an inhibitor of prokaryotic DNA gyrase showed about six times less EC50 value in Eh than that of human cells. The parasite’s notable susceptibility to prokaryotic topoisomerase drugs in comparison to human cells opens up the scope to study this invaluable enzyme in the light of an antiamoebic target.