bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Escitalopram and Relearning on Cortical and Subcortical Grey Matter in Healthy Humans
Authors: Vanicek T , Reed MB , Seiger R , Godbersen M , Klöbl M , Unterholzner J , Spurny B , Gryglewski G , Handschuh P , Kraus C , Stimpfl T , Rupprecht R , Kasper S , Lanzenberger R 
Published: April 2021

AbstractThe antidepressant effect of selective serotonin reuptake inhibitors (SSRI) is related to increased neuroplasticity during relearning. Stress-induced dendritic atrophy in key brain areas for learning and memory such as the hippocampus and prefrontal cortex is reversed by SSRI treatment. This finding is accompanied by behavioral stabilization. The aim of this study was to investigated serotonergic modulation effects on structural neuroplasticity (cortical thickness, subcortical volumes) during relearning in healthy subjects. Participants performed daily associative learning tasks over 3 weeks followed by a 3-week relearning phase combined with intake of the SSRI escitalopram or placebo. Evidence suggests that SSRIs promote the brains susceptibility to change on the basis of environment factors. We found no effect of SSRI on grey matter measures during relearning. Here, non-findings might be a consequence of the implemented intensity and duration of study interventions. With sparse literature on healthy participants in this field, future studies will have to further elucidate SSRIs properties on relearning and structural neuroplasticity.
Antagonism of GluK1-containing Kainate Receptors Reduces Ethanol Consumption by Modulating Ethanol Reward and Withdrawal
Authors: Cardé Natalia A. Quijano , Perez Erika E. , Feinn Richard , Kranzler Henry R. , Biasi Mariella De 
Published: April 2021

ABSTRACTAlcohol use disorder (AUD) is a neuropsychiatric condition affecting millions of people worldwide. Topiramate (TPM) is an antiepileptic drug that has been shown to reduce ethanol drinking in humans. However, TPM is associated with a variety of adverse effects due to its interaction with many receptor systems and intracellular pathways. Thus, a better understanding of the role of TPM’s main molecular targets in AUD could yield better therapeutic tools. GluK1-containing kainate receptors (GluK1*KARs) are non-selectively inhibited by TPM, and genetic association studies suggest that this receptor system could be targeted to reduce drinking in AUD patients. We examined the efficacy of LY466195, a selective inhibitor of GluK1*KAR, in reducing ethanol consumption in the intermittent two-bottle choice paradigm in mice. The effect of LY466195 on various ethanol-related phenotypes was investigated by quantification of alcohol intake, physical signs of withdrawal, conditioned place preference (CPP) andin vivomicrodialysis in the nucleus accumbens. Selective GluK1*KAR inhibition reduced ethanol intake and preference in a dose-dependent manner. LY466195 treatment attenuated the physical manifestations of ethanol withdrawal and influenced the rewarding properties of ethanol. Interestingly, LY466195 injection also normalized changes in dopamine levels in response to acute ethanol in ethanol-dependent mice, but had no effect in ethanol-naïve mice, suggesting ethanol state-dependent effects. The data point to GluK1*KARs as an attractive pharmacological target for the treatment of AUD.
Connectivity networks and delineation of distinct coastal provinces along the Indian coastline using large-scale Lagrangian transport simulations
Authors: Bharti D. K. , Guizien Katell , Aswathi-Das M. T. , Vinayachandran P. N. , Shanker Kartik 
Published: April 2021

AbstractOcean circulation defines the scale of population connectivity in marine ecosystems, and is essential for conservation planning. We performed Lagrangian transport simulations and built connectivity networks to understand the patterns of oceanographic connectivity along the Indian coastline. In these networks, nodes are coastal polygons and the edges connecting them represent the magnitude of larval transfer between them. We assessed the variation in connectivity networks within and between two monsoonal seasons, across El Niño–Southern Oscillation (ENSO) years and for pelagic larval durations (PLD) up to 50 days. We detected well-connected communities, mapped frequent connectivity breaks and ranked coastal areas by their functional role using network centrality measures. Network characteristics did not differ based on the ENSO year, but varied based on season and PLD. Large scale connectance (entire Indian coastline) was small, ranging from 0.5% to 3.4%, and the number of cohesive coastal communities decreased from 60 (PLD <4 days) to 30 (PLD >20 days) with increasing PLD. Despite intra-seasonal variation in connectivity breaks, four disconnected provinces were consistently identified across the entire PLD range, which partially overlapped with observed genetic and biogeographic breaks along the Indian coastline. Our results support the adoption of an adaptive regional management framework guided by fine-scale analysis of connectivity within the four provinces delineated in the present study. A few sites within each province displayed notably higher centrality values than other nodes of the network, but showed variation with season and PLD, and could be targeted for national and transnational conservation and management plans.
Hippocampal gamma-band oscillopathy in a mouse model of Fragile X Syndrome
Authors: Pollali Evangelia , Hollnagel Jan-Oliver , Çalışkan Gürsel 
Published: April 2021

AbstractFragile X syndrome (FXS) is the most common inherited form of intellectual disability arising from the loss of fragile X mental retardation protein (FMRP), a protein that plays a central role in neuronal function and plasticity. FXS patients show sensory hypersensitivity, hyperarousal and hippocampus-dependent learning deficits that can be recapitulated in the FMR1 KO mice. Enhanced metabotropic glutamate receptor (mGluR) signaling and muscarinic acetylcholine receptor (mAChR) signaling in the FMR1 KO mouse are implicated as the primary causes of the disease pathogenesis. Furthermore, glutamatergic kainate receptor (KAR) function is reduced in the cortex of the FMR1 KO mice. Of note, activation of these signaling pathways leads to slow gamma-range oscillations in the hippocampusin vitroand abnormal gamma oscillations have been reported in FMR1 KO mice and patients with FXS. Thus, we hypothesized that aberrant activation of these receptors leads to the observed gamma oscillopathy. We recorded gamma oscillations induced by either cholinergic agonist carbachol (CCh), mGluR1/5 agonist Dihydroxyphenylglycine (DHPG) or ionotropic glutamatergic agonist KA from the hippocampal CA3 in WT and FMR1 KO micein vitro. We show a specific increase in the power of DHPG and CCh-induced gamma oscillations and reduction in the synchronicity of gamma oscillations induced by KA. We further elucidate an aberrant spiking activity during CCh-induced and kainate-induced gamma oscillations which may underlie the altered gamma oscillation synchronization in the FMR1 KO mice. Last, we also noted a reduced incidence of spontaneously-occurring hippocampal sharp wave-ripple events. Our study provides further evidence for aberrant hippocampal rhythms in the FMR1 KO mice and identifies potential signaling pathways underlying gamma band oscillopathy in FXS.
The P1 and P2 helices of the Guanidinium-II riboswitch interact in a ligand-dependent manner
Authors: Fuks Christin , Falkner Sebastian , Schwierz Nadine , Hengesbach Martin 
Published: April 2021

ABSTRACTRiboswitch RNAs regulate gene expression by conformational changes induced by environmental conditions and specific ligand binding. The guanidine-II riboswitch is proposed to bind the small molecule guanidinium and to subsequently form a kissing loop interaction between the P1 and P2 hairpins. While an interaction was shown for isolated hairpins in crystallization and EPR experiments, an intrastrand kissing loop formation has not been demonstrated. Here, we report the first evidence of this interactionin cisin a ligand and Mg2+dependent manner. Using single-molecule FRET spectroscopy and detailed structural information from coarse-grained simulations, we observe and characterize three interconvertible states representing an open and kissing loop conformation as well as a novel Mg2+dependent state for the guanidine-II riboswitch fromE. coli. The results further substantiate the proposed switching mechanism and provide detailed insight into the regulation mechanism for the guanidine-II riboswitch class. Combining single molecule experiments and coarse-grained simulations therefore provides a promising perspective in resolving the conformational changes induced by environmental conditions and to yield molecular insights into RNA regulation.
How adaptation, training, and customization contribute to benefits from exoskeleton assistance
Authors: Poggensee Katherine L. , Collins Steven H. 
Published: April 2021

AbstractExoskeletons can enhance human mobility, but we still know little about why they are effective. For example, we do not know the relative importance of training, how much is required, or what type is most effective; how people adapt with the device; or the relative benefits of customizing assistance. We conducted experiments in which naïve users learned to walk with ankle exoskeletons under one of three training regimens characterized by different levels of variation in device behavior. Assistance was also customized for one group. Following moderate-variation training, the benefits of customized assistance were large; metabolic rate was reduced by 39% compared to walking with the exoskeleton turned off. Training contributed about half of this benefit and customization about one quarter; a generic controller reduced energy cost by 10% before training and 31% afterwards. Training required much more exposure than typical of exoskeleton studies, about 109 minutes of assisted walking. Type of training also had a strong effect; the low-variation group required twice as long as the moderate-variation group to become expert, while the high-variation group never acquired this level of expertise. Curiously, all users adapted in a way that resulted in less mechanical power from the exoskeleton as they gained expertise. Customizing assistance required less time than training for all parameters except peak torque magnitude, which grew slowly over the study, suggesting a longer time-scale adaptation in the person. These results underscore the importance of training to the benefits of exoskeleton assistance and suggest the topic deserves more attention.
Dual reference method for high precision infrared measurement of leaf surface temperature under field conditions
Authors: Muller Jonathan D. , Rotenberg Eyal , Tatarinov Fyodor , Vishnevetsky Irina , Dingjan Tamir , Kribus Abraham , Yakir Dan 
Published: April 2021

AbstractTemperature is a key control over biological activities from the cellular to the ecosystem scales. However, direct, high precision measurements of surface temperature of small objects such as leaves under field conditions with large variations in ambient conditions remain rare. Contact methods such as thermocouples are prone to large errors. The use of non-contact remote sensing methods such as thermal infrared measurements provides an ideal solution, but their accuracy has been low (in the order of ~2 °C) due to necessity for corrections for material emissivity and fluctuations in background radiation (Lbg).A novel ‘dual-reference’ method was developed to increase the accuracy of infrared needle-leaf surface temperature measurements in the field. It accounts for variations inLbgand corrects for the systematic camera offset using two reference plates.We accurately captured surface temperature and leaf-to-air temperature differences of needle-leaves in a forest ecosystem with large diurnal and seasonal temperature fluctuations with an uncertainty of ±0.23 and ±0.25 °C, respectively.Routine high precision leaf temperature measurements even under harsh field conditions, such as demonstrated here, opens the way for investigating a wide range of leaf-scale processes and its dynamics.
Acute stress affects peripersonal space representation
Authors: Ellena Giulia , Bertoni Tommaso , Durand-Ruel Manon , Thoresen John , Sandi Carmen , Serino Andrea 
Published: April 2021

SummaryPeripersonal space (PPS) is the region of space surrounding the body. It has a dedicated multisensory-motor representation, whose purpose is to predict and plan interactions with the environment, and which can vary depending on environmental circumstances. Here, we investigated the effect on the PPS representation of an experimentally induced stress response. We assessed PPS representation in healthy humans, before and after a stressful manipulation, by quantifying visuotactile interactions as a function of the distance from the body, while monitoring salivary cortisol concentration. Participants, who showed a cortisol stress response, presented enhanced visuotactile integration for stimuli close to the body and reduced for far stimuli. Conversely, individuals, with a less pronounced cortisol response, showed a reduced difference in visuotactile integration between the near and the far space. In our interpretation, physiological stress resulted in a freezing-like response, where multisensory-motor resources are allocated only to the area immediately surrounding the body.
iPLA2-VIA is required for healthy aging in neurons, muscle, and female germline inDrosophila melanogaster
Authors: Banerjee Surya , Schonbrun Adina , Eizadshenass Sogol , Benji Shimshon , Cantor Yaakov Tzvi , Eliach Liam , Lubin Matthew , Narrowe Zev , Purow Jeremy , Shulman Benjamin , Wiener Leib , Steinhauer Josefa 
Published: April 2021

AbstractNeurodegenerative disease (ND) is a growing health burden worldwide, but its causes and treatments remain elusive. Although most cases of ND are sporadic, rare familial cases have been attributed to single genes, which can be investigated in animal models. We have generated a new mutation in the calcium-independent phospholipase A2(iPLA2) VIA geneCG6718, theDrosophila melanogasterortholog of humanPLA2G6/PARK14, mutations in which cause a suite of NDs collectively calledPLA2G6-associated neurodegeneration (PLAN). Our mutants display age-related loss of climbing ability, a symptom of neurodegeneration in flies. Although phospholipase activity commonly is presumed to underlie iPLA2-VIA function, locomotor decline in our mutants is rescued by a transgene carrying a serine-to-alanine mutation in the catalytic residue, suggesting that important functional aspects are independent of phospholipase activity. Additionally, we find that iPLA2-VIA knockdown in either muscle or neurons phenocopies locomotor decline with age, demonstrating its necessity in both neuronal and non-neuronal tissues. Furthermore, RNA in situ hybridization shows high endogenousiPLA2-VIAmRNA expression in adult germ cells, and transgenic HA-tagged iPLA2-VIA colocalizes with mitochondria there. Mutant males are fertile with normal spermatogenesis, while fertility is reduced in mutant females. Mutant female germ cells display age-related mitochondrial aggregation, loss of mitochondrial potential, and elevated cell death. These results suggest that iPLA2-VIA is important for germline mitochondrial integrity inDrosophila,which may be relevant for understanding how PLAN develops.
Enhancer RNAs stimulate Pol II pause release by harnessing multivalent interactions to NELF
Authors: Gorbovytska Vladyslava , Kim Seung-Kyoon , Kuybu Filiz , Götze Michael , Um Dahun , Kang Keunsoo , Pittroff Andreas , Schneider Lisa-Marie , Leitner Alexander , Kim Tae-Kyung , Kuhn Claus-D. 
Published: April 2021

ABSTRACTEnhancer RNAs (eRNAs) are long non-coding RNAs that originate from enhancers. Although eRNA transcription is a canonical feature of activated enhancers, the molecular features required for eRNA function and the mechanism of how eRNAs impinge on target gene transcription have not been established. Thus, using eRNA-dependent RNA polymerase II (Pol II) pause release as a model, we examined the requirement of sequence, structure and length of eRNAs for their ability to stimulate Pol II pause release by detaching NELF from paused Pol II. We found eRNA not to exert their function through common structural or sequence motifs. Instead, efficient NELF release requires a single eRNA molecule that must contain unpaired guanosines to make multiple, allosteric contacts with several NELF subunits. By revealing the molecular determinants for eRNA function, our study mechanistically links eRNAs to Pol II pause release and provides new insight into the regulation of metazoan transcription.
Molecular mechanisms controlling the biogenesis of the TGF-β signal Vg1
Authors: Dingal P. C. Dave P. , Carte Adam N. , Montague Tessa G. , Lim Suan Medel B. , Schier Alexander F. 
Published: April 2021

AbstractThe TGF-beta signals Vg1 (Dvr1/Gdf3) and Nodal form heterodimers to induce vertebrate mesendoderm. The Vg1 proprotein is a monomer retained in the endoplasmic reticulum (ER) and is processed and secreted upon heterodimerization with Nodal, but the mechanisms underlying Vg1 biogenesis are largely elusive. Here we clarify the mechanisms underlying Vg1 retention, processing, secretion and signaling, and introduce a Synthetic Processing (SynPro) system that enables the programmed cleavage of ER-resident and extracellular proteins. First, we find that Vg1 can be processed by intra- or extracellular proteases. Second, Vg1 can be processed without Nodal but requires Nodal for secretion and signaling. Third, Vg1-Nodal signaling activity requires Vg1 processing, whereas Nodal can remain unprocessed. Fourth, Vg1 employs exposed cysteines, glycosylated asparagines, and BiP chaperone-binding motifs for monomer retention in the ER. These observations suggest two mechanisms for rapid mesendoderm induction: chaperone-binding motifs help store Vg1 as an inactive but ready-to-heterodimerize monomer in the ER, and the flexibility of Vg1 processing location allows efficient generation of active heterodimers both intra- and extracellularly. These results establish SynPro as a new in vivo processing system and define molecular mechanisms and motifs that facilitate the generation of active TGF-beta heterodimers.SignificanceThe TGF-beta family members Nodal and Vg1 are the major inducers of mesendoderm formation during vertebrate embryogenesis. We previously established that the Vg1 proprotein is retained in the endoplasmic reticulum (ER), and that Nodal and Vg1 form heterodimers to pattern the early embryo. However, the mechanisms underlying the retention, processing, secretion, and signaling of Vg1 have been unclear. We found two mechanisms that embryos use to efficiently generate active Nodal-Vg1 heterodimers: (1) Vg1 employs its chaperone-binding motifs to ensure its retention as a ready-to-heterodimerize monomer in the ER; (2) Using a newly devised Synthetic Processing (SynPro) System, we found that Vg1 must be processed for signaling to occur, but its processing location is flexible.
Light Attention Predicts Protein Location from the Language of Life
Authors: Stärk Hannes , Dallago Christian , Heinzinger Michael , Rost Burkhard 
Published: April 2021

AbstractSummaryAlthough knowing where a protein functions in a cell is important to characterize biological processes, this information remains unavailable for most known proteins. Machine learning narrows the gap through predictions from expert-designed input features leveraging information from multiple sequence alignments (MSAs) that is resource expensive to generate. Here, we showcased using embeddings from protein language models (pLMs) for competitive localization prediction without MSAs. Our lightweight deep neural network architecture used a softmax weighted aggregation mechanism with linear complexity in sequence length referred to as light attention (LA). The method significantly outperformed the state-of-the-art (SOTA) for ten localization classes by about eight percentage points (Q10). So far, this might be the highest improvement ofjust embeddingsover MSAs. Our new test set highlighted the limits of standard static data sets: while inviting new models, they might not suffice to claim improvements over the SOTA.AvailabilityOnline predictions are available athttp://embed.protein.properties. Predictions for the human proteome are available athttps://zenodo.org/record/5047020. Code is provided athttps://github.com/HannesStark/protein-localization.
Abscisic acid modulates auxin-responsive hypocotyl elongation
Authors: Emenecker Ryan J. , Cammarata Joseph , Yuan Irene , Strader Lucia C. 
Published: April 2021

AbstractAuxin regulates many aspects of plant growth and development in concert with other plant hormones. Auxin interactions with these other phytohormones to regulate distinct processes is not fully understood. Using a forward genetics screen designed to identify seedlings resistant to the suppressive effects of auxin on dark-grown hypocotyl elongation, we identified a mutant defective inABA ALDEHYDE OXIDASE3(AAO3), which encodes for the enzyme that carries out the final step in the biosynthesis of the plant hormone abscisic acid (ABA). We found that all examined ABA deficient mutants display resistance to the inhibitory effects of auxin on dark-grown hypocotyl elongation, suggesting that aspects of ABA signaling are downstream of auxin in regulating dark-grown hypocotyl elongation. Conversely, these mutants display wild type responsiveness to auxin in root elongation assays, suggesting that ABA does not act downstream of auxin in regulating elongation of the root. Our RNA-seq analysis suggests that many auxin-repressed genes in the hypocotyl require an intact ABA pathway for full repression. Our results suggest a model in which auxin partially requires intact ABA biosynthesis in order to regulate hypocotyl elongation, but not to regulate primary root elongation, suggesting that the genetic interactions between these two pathways are tissue-dependent.
A new paradoxosomatid millipede,Manikidesmus suriensis(Polydesmida: Paradoxosomatidae) from West Bengal, India
Authors: Bhakat Somnath 
Published: April 2021

AbstractA new genus and species of the family Paradoxosomatidae from southern part of West Bengal, India is described. The new genusManikidesmusgen. n. is diagnosed by combination of following characters: reduced paranota, distinct pleural keel, unpaired sternal lamella on 5thsternite, prefemur with setal brush, setal brush on tibia and tarsus in male, lamina medialis long straight with a curved hook, expanded post femoral lamina with a spine and tibiotarsus with a spine on the distofemoral process.The genus is distinguished from its Indian congeners by one or more diagnosed characters. InManikidesmus suriensis, sp. n. tibia and tarsus bear setal brush in male (vs. absent inOxidusandChondromorpha), gonopod femur short, flat and without post femoral demarcation (vs. long, thin cylindrical with post femoral demarcation inPolydrepanumandOrthomorpha), tibiotarsus of gonopod long and a spine on the distofemoral process (vs. short and without spine inAnoplodesmus). InKronopolites, coxa of gonopod densely bristled, collum with two rows of long bristles, femur long, slender and with a spine. All these characters are absent in the present genus. InStreptogonopus, gonopod femorite is distinctly demarcated from post femorite region and solenomere is twisted with solenophore but in the present species, femorite is not be separated from post femorite region and solenomere is free from solenophore.