bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant motor contagion of emotions in psychopathy and high-functioning autism
Authors: Sun Lihua , Lukkarinen Lasse , Noppari Tuomo , Nazari-Farsani Sanaz , Putkinen Vesa , Seppälä Kerttu , Hudson Matthew , Tani Pekka , Lindberg Nina , Karlsson Henry K. , Hirvonen Jussi , Salomaa Marja , Venetjoki M. Niina , Lauerma Hannu , Tiihonen Jari , Nummenmaa Lauri 
Published: July 2021

AbstractPsychopathy and autism are both associated with aberrant social interaction and communication, yet only psychopaths are markedly antisocial and violent. Here we compared the functional neural alterations underlying these two different phenotypes with distinct patterns of socioemotional difficulties. We studied 19 incarcerated male offenders with high psychopathic traits, 20 males with high-functioning autism and 19 age-matched healthy controls. All groups underwent functional magnetic resonance imaging while they viewed dynamic happy, angry and disgust facial expressions or listened to laughter and crying sounds. Psychopathy was associated with reduced somatomotor responses to almost all expressions, while subjects with autism demonstrated less marked and emotion-specific alterations in the somatomotor area. These data suggest that psychopathy and autism involve both common and distinct functional alterations in the brain networks involved in socioemotional processing.
Cyp26b1 restrains murine heart valve growth during development
Authors: Ahuja Neha , Hiltabidle Max S. , Rajasekhar Hariprem , Barlow Haley R. , Daniel Edward , Voss Sophie , Cleaver Ondine , Maynard Caitlin 
Published: July 2021

ABSTRACTEndothelial cells (ECs) are critical to proper heart valve development, directly contributing to the mesenchyme of the cardiac cushions, which progressively transform into mature valves. To date, investigators have lacked useful markers of valve ECs to fully evaluate their contributions during valve morphogenesis. As a result, it has been unclear whether the well-characterized regional differentiation of valves correlates with any endothelial domains in the heart. Furthermore, it has been difficult to ascertain whether endothelial heterogeneity in the heart influences underlying mesenchymal zones in an angiocrine manner. To identify regionally expressed EC genes in the heart valves, we screened publicly available databases and assembled a toolkit of endothelial-enriched genes. We identified Cyp26b1 as one of many endothelial enriched genes found to be expressed in the endocardium of the developing cushions and valves. Here, we show that Cyp26b1 is required for normal heart valve development. Genetic ablation of Cyp26b1 in mouse embryos leads to abnormally thickened aortic valve leaflets, which is due in part to increased endothelial and mesenchymal cell proliferation in the remodeling valves. In addition, Cyp26b1 mutant hearts display ventricular septal defects (VSDs) in a portion of null embryos. We show that loss of Cyp26b1 results in upregulation of retinoic acid (RA) target genes, supporting the observation that Cyp26b1 has RA-dependent roles. Together, this work identifies a novel role for Cyp26b1 in heart valve morphogenesis. Understanding the spatiotemporal expression dynamics of cardiac EC genes will likely prove useful to the investigation of both normal as well as dysfunctional heart valve development.HIGHLIGHTS· A mouse heart valve gene expression atlas can be generated with publicly available online tools, such as Genepaint and other gene expression databases.· Endothelium of developing mouse heart valves is regionally heterogeneous.· Cyp26b1 is expressed in the endocardial/endothelial lining of developing heart valves.· Loss of Cyp26b1 leads to significant enlargement of aortic valves and to ventricular septal defects.· Cyp26b1 represses cell proliferation in valve mesenchyme.· Retinoic acid targets are upregulated in Cyp26b1-/- heart valves, indicating dysregulation of RA metabolism.
The Cl--channel TMEM16A controls the generation of cochlear Ca2+ waves and promotes the refinement of auditory brainstem networks
Authors: Maul Alena , Jovanovic Saša , Huebner Antje K. , Strenzke Nicola , Moser Tobias , Rübsamen Rudolf , Hübner Christian A. 
Published: July 2021

SummaryBefore hearing onset (postnatal day 12 in mice), inner hair cells (IHC) spontaneously fire action potentials thereby driving pre-sensory activity in the ascending auditory pathway. The rate of IHC action potential bursts is modulated by inner supporting cells (ISC) of Kölliker’s organ through the activity of the Ca2+ activated Cl- channel TMEM16A. Here we show that conditional deletion of Tmem16a in mice disrupts the generation of Ca2+ waves within Kölliker’s organ, reduces the burst firing activity and the frequency-selectivity of auditory brainstem neurons in the medial nucleus of the trapezoid body (MNTB), and also impairs the refinement of MNTB projections to the lateral superior olive (LSO). These results reveal the importance of the activity of Kölliker’s organ for the refinement of central auditory connectivity. In addition, our study suggests a mechanism for the generation of Ca2+ waves, which may also apply to other tissues expressing TMEM16A.
Identification of potential carboxylic acid-containing drug candidate to design novel competitive NDM inhibitors: An in-silico approach comprising combined virtual screening and molecular dynamics simulation
Authors: Vasudevan Karthick , Basu Soumya , Arumugam Amala , Naha Aniket , Ramaiah Sudha , Anbarasu Anand , Veeraraghavan Balaji 
Published: July 2021

ABSTRACTMetallo-β-lactamases (MBLs) producing bacteria especially the ones with New Delhi metallo-beta-lactamase-1 (NDM-1) and its variants can potentially hydrolyse all the major β-lactam antibiotics, ultimately escalating anti-microbial resistance world-wide. There is a dearth of approved inhibitors to combat NDM and other MBLs producing bacteria. Hence we focussed to find novel inhibitor(s) in-silico which can potentially suppress the activity of NDM/ MBLs. 2400 compounds were virtually screened to identify a promising carboxylic acid-containing compound (CID-53986787) analogous to NDM antagonist Captopril. Our lead compound can bind adjacent to the active site zinc ions (Zn1 and Zn2) in all highly resistant NDM variants. CID-53986787 possesses ~5-8% higher binding affinity than Captopril, exhibiting molecular interactions with crucial residues that can destabilize the hydrolytic activity of NDM. CID-53986787 was virtually evaluated to ascertain its safe pharmacological/ toxicity profile. Molecular dynamics simulation studies elucidated its stable interaction with the target protein (NDM-1).
Molecular Determinants of Complexin Clamping in Reconstituted Single-Vesicle Fusion
Authors: Bera Manindra , Ramakrishnan Sathish , Coleman Jeff , Krishnakumar Shyam S. , Rothman James E. 
Published: July 2021

ABSTRACTPreviously we reported that Synaptotagmin-1 and Complexin synergistically clamp the SNARE assembly process to generate and maintain a pool of docked vesicles that fuse rapidly and synchronously upon Ca2+ influx (Ramakrishnan et al. 2020). Here using the same in vitro single-vesicle fusion assay, we establish the molecular details of the Complexin clamp and its physiological relevance. We find that a delay in fusion kinetics, likely imparted by Synaptotagmin-1, is needed for Complexin to block fusion. Systematic truncation/mutational analyses reveal that continuous alpha-helical accessory-central domains of Complexin are essential for its inhibitory function and specific interaction of the accessory helix with the SNAREpins, analogous to the trans clamping model, enhances this functionality. The c-terminal domain promotes clamping by locally elevating Complexin concentration through interactions with the membrane. Further, we find that Complexin likely contributes to rapid Ca2+-synchronized vesicular release by preventing un-initiated fusion rather than by directly facilitating vesicle fusion.
Disturbance-based management of ecosystem services and disservices in partial nitritation anammox biofilms
Authors: Suarez Carolina , Sedlacek Christopher J. , Gustavsson David J. I. , Eiler Alexander , Modin Oskar , Hermansson Malte , Persson Frank 
Published: July 2021

ABSTRACTThe resistance and resilience provided by functional redundancy, a common feature of microbial communities, is not always advantageous. An example is nitrite oxidation in partial nitritation-anammox (PNA) reactors during wastewater treatment, where suppression of nitrite oxidizers likeNitrospirais sought. In these ecosystems, biofilms provide microhabitats with oxygen gradients, allowing the coexistence aerobic and anaerobic bacteria. We designed a disturbance experiment where PNA biofilms treating water from a high rate activated sludge process removing organic matter (mainstream wastewater), were constantly or intermittently exposed to the effluent of anaerobic sewage sludge digestion dewatering (sidestream wastewater), which has been proposed to inhibit nitrite oxidizers. With increasing sidestream exposure we observed decreased abundance, alpha-diversity, functional versatility, and hence functional redundancy, amongNitrospirain the PNA biofilms, while the opposite patterns were observed for anammox bacteria withinBrocadia. At the same time, species turnover was observed for the aerobic ammonia-oxidizingNitrosomonaspopulations. The different exposure regimens were associated with metagenomic assembled genomes ofNitrosomonas, Nitrospira, andBrocadia, encoding genes related to N-cycling, substrate usage, and osmotic stress response, possibly explaining the three different patterns by niche differentiation. These findings imply that disturbances can be used to manage the functional redundancy of biofilm microbiomes in a desirable direction, which should be considered when designing operational strategies for wastewater treatment.
The structurome of a Clostridium difficile phage and the remarkable accurate prediction of its novel phage receptor-binding protein
Authors: Dowah Ahmed S. A. , Xia Guoqing , Ali Ali Abdul Kareem , Thanki Anisha M. , Shan Jinyu , Millard Andy , Petersen Bent , Sicheritz-Pontén Thomas , Wallis Russell , Clokie Martha R. J. 
Published: July 2021

AbstractAs natural bacterial predators, bacteriophages have the potential to be developed to tackle antimicrobial resistance, but our exploitation of them is limited by understanding their vast uncharacterised genetic diversity1,2. Fascinatingly, this genetic diversity reflects many ways that phages can make proteins, performing similar functions that together form the familiar phage particle. Critical to infection are phage receptor-binding proteins (RBPs) that bind bacterial ‘receptors’ and initiate bacterial entry3. Here we identified and characterised Gp22, a novel RBP for phage CDHS-1 that infects pathogenic C. difficile, but that had no recognisable RBPs. We showed that Gp22 antibodies neutralised CDHS-1 infection and used immunogold-labelling and transmission electron microscopy to identify their location on the capsid. The Gp22 three-dimensional structure was resolved by X-ray crystallography revealing a new RBP class with an N-terminal L-shaped α-helical superhelix domain and a C-terminal Mg2+-binding domain. The findings provide novel insights into C. difficile phage biology and phage-host interactions. This will facilitate optimal phage development and future engineering strategies4,5. Furthermore, the AlphaFold2-predicted Gp22 structure, which was strikingly accurate, paves the way for a structurome based transformation and guidance of future phage studies where many proteins lack sequence homology but have recognisable protein structures.
A framework for assessing the skill and value of operational recruitment forecasts
Authors: Kiaer Christian , Neuenfeldt Stefan , Payne Mark R. 
Published: July 2021

AbstractForecasting variation in the recruitment to fish stocks is one of the most challenging and long-running problems in fisheries science and essentially remains unsolved today. Traditionally recruitment forecasts are developed and evaluated based on explanatory and goodness-of-fit approaches that do not reflect their ability to predict beyond the data on which they were developed. Here we propose a new generic framework that allows the skill and value of recruitment forecasts to be assessed in a manner that is relevant to their potential use in an operational setting. We assess forecast skill based on predictive power using a retrospective forecasting approach inspired by meterology, and emphasise the importance of assessing these forecasts relative to a baseline. We quantify the value of these forecasts using an economic cost-loss decision model that is directly relevant to many forecast users. We demonstrate this framework using four stocks of lesser sandeel (Ammodytes marinus) in the North Sea, showing for the first time in an operationally realistic setting that skilful and valuable forecasts are feasible in two of these areas. This result shows the ability to produce valuable short-term recruitment forecasts, and highlights the need to revisit our approach to and understanding of recruitment forecasting.
Population-level inference for home-range areas
Authors: Fleming C. H. , Deznabi I. , Alavi S. , Crofoot M. C. , Hirsch B. T. , Medici E. P. , Noonan M. J. , Kays R. , Fagan W. F. , Sheldon D. , Calabrese J. M. 
Published: July 2021

AbstractHome-range estimates are a common product of animal tracking data, as each range informs on the area needed by a given individual. Population-level inference on home-range areas—where multiple individual home-ranges are considered to be sampled from a population—is also important to evaluate changes over time, space, or covariates, such as habitat quality or fragmentation, and for comparative analyses of species averages. Population-level home-range parameters have traditionally been estimated by first assuming that the input tracking data were sampled independently when calculating home ranges via conventional kernel density estimation (KDE) or minimal convex polygon (MCP) methods, and then assuming that those individual home ranges were measured exactly when calculating the population-level estimates. This conventional approach does not account for the temporal autocorrelation that is inherent in modern tracking data, nor for the uncertainties of each individual home-range estimate, which are often large and heterogeneous.Here, we introduce a statistically and computationally efficient framework for the population-level analysis of home-range areas, based on autocorrelated kernel density estimation (AKDE), that can account for variable temporal autocorrelation and estimation uncertainty.We apply our method to empirical examples on lowland tapir (Tapirus terrestris), kinkajou (Potos flavus), white-nosed coati (Nasua narica), white-faced capuchin monkey (Cebus capucinus), and spider monkey (Ateles geoffroyi), and quantify differences between species, environments, and sexes.Our approach allows researchers to more accurately compare different populations with different movement behaviors or sampling schedules, while retaining statistical precision and power when individual home-range uncertainties vary. Finally, we emphasize the estimation of effect sizes when comparing populations, rather than mere significance tests.
Transcriptional heterogeneity of ventricular zone cells throughout the embryonic mouse forebrain
Authors: Lee Dongjin R. , Rhodes Christopher T. , Mitra Apratim , Zhang Yajun , Maric Dragan , Dale Ryan K. , Petros Timothy J. 
Published: July 2021

SUMMARYThe ventricular zone (VZ) of the nervous system contains radial glia cells that were originally considered relatively homogenous in their gene expression. However, a detailed characterization of transcriptional diversity in these VZ cells has not been reported. Here, we performed single-cell RNA sequencing to characterize transcriptional heterogeneity of neural progenitors within the VZ and subventricular zone (SVZ) of the mouse embryonic cortex and ganglionic eminences (GEs). By using a transgenic mouse line to enrich for VZ cells, we detect significant transcriptional heterogeneity within VZ and SVZ progenitors, both between forebrain regions and within spatial subdomains of specific GEs. Additionally, we observe differential gene expression between E12.5 and E14.5 VZ cells, which could provide insights into temporal changes in cell fate. Together, our results reveal a previously unknown spatial and temporal genetic diversity of telencephalic VZ cells that will aid our understanding of initial fate decisions in the forebrain.
Phosphorylation of STIM1 at ERK/CDK sites is dispensable for cell migration and ER partitioning in mitosis
Authors: Hammad Ayat S. , Yu Fang , Botheju Welathanthrige S. , Elmi Asha , Alcantara-Adap Ethel , Machaca Khaled 
Published: July 2021

ABSTRACTStore-operated Ca2+ entry (SOCE) is a ubiquitous Ca2+ influx required for multiple physiological functions including cell motility. SOCE is activated in response to depletion of intracellular Ca2+ stores following the activation of endoplasmic reticulum (ER) Ca2+ sensor STIM1 which recruits the plasma membrane (PM) Ca2+ channel Orai1 at ER-PM junctions to induce Ca2+ influx. STIM1 is phosphorylated dynamically and this phosphorylation has been implicated in several processes including SOCE inactivation during M-phase, maximal SOCE activation, ER segregation during mitosis, and cell migration. Human STIM1 has 10 Ser/Thr residues in its cytosolic domain that match the ERK/CDK consensus phosphorylation. We recently generated a mouse knock-in line where wild-type STIM1 was replaced by a non-phosphorylatable STIM1 with all 10 S/T mutated to Ala (STIM1-10A). Here, we generate mouse embryonic fibroblasts (MEF) the STIM1-10A mouse line and a control MEF line (WT) that express wild-type STIM1 from a congenic mouse strain. These lines offer a unique model to address the role of STIM1 phosphorylation at endogenous expression and modulation levels in contrast to previous studies that relied mostly on overexpression. We show that STIM1 phosphorylation at ERK/CDK sites is not required for SOCE activation, cell migration, or ER partitioning during mitosis. These results rule out STIM1 phosphorylation as a regulator of SOCE, migration and ER distribution in mitosis.
CCAR-1 has a novel role in regulating the Caenorhabditis elegans germline
Authors: Lugano Doreen I. , Deonarine Andrew , Park Margaret A. , Westerheide Sandy D. 
Published: July 2021

1.ABSTRACTThe Cell Division Cycle and Apoptosis Regulator (CCAR) protein family members are putative transcription regulators that have been characterized for modulating the cell cycle, apoptosis, metabolism, and the heat shock response. Mammals have two CCAR family members, CCAR1 and CCAR2/DBC1, that evolved from the founding family member CCAR-1 that is expressed in Caenorhabditis elegans. Mammalian CCAR2, the most well-studied family member, has been shown to regulate genes involved in metabolism in cultured cells. However, the regulation of gene expression by CCAR family members at an organismal level is unknown. Here, we use whole transcriptome RNA sequencing to examine the effects of CCAR-1 on gene expression in Caenorhabditis elegans. We show that CCAR-1 regulates germline transcription, reproduction, lifespan, and DNA-damage induced apoptosis. This study shows the role of CCAR-1 in vital physiological functions in the C. elegans germline that have not been investigated before.
Computational analysis to enhance the compressible flow over an aerofoil surface
Authors: Marimuthu Siva , Chinnathambi Dhavamani 
Published: July 2021

Purpose
Since the inception of aerospace engineering, reducing drag is of eternal importance. Over the years, researchers have been trying to improve the aerodynamics of National Advisory Committee for Aeronautics (NACA) aerofoils in many ways. It is proved that smooth-surfaced NACA 0012 aerofoil produces more drag in compressible flow. Recent research on shark-skin pattern warrants a feasible solution to many fluid-engineering problems. Several attempts were made by many researchers to implement the idea of shark skin in the form of coatings, texture and more. However, those ideas are at greater risk when it comes to wing maintenance. The purpose of this paper is to implement a relatively larger biomimetic pattern which would make way for easy maintenance of patterned wings with improved performance.

Design/methodology/approach
In this paper, two biomimetic aerofoils are designed by optimizing the surface pattern of shark skin and are tested at different angles of attack in the computational flow domain.

Findings
The results of the biomimetic aerofoils prove that viscous and total drag can be reduced up to 33.08% and 3.68%, respectively, at high subsonic speed when validated against a NACA 0012 aerofoil. With the ample effectiveness of patched shark-skin pattern, biomimetic aerofoil generates as high as 10.42% lift than NACA 0012.

Originality/value
In this study, a feasible shark-skin pattern is constructed for NACA 0012 in a transonic flow regime. Computational results achieved using the theoretical model agree with experimental data.
User participation, knowledge management capability and service innovation: e-commerce enterprises in the digital age
Authors: Xin Xiaohua , Miao Xiaoming , Chen Qian , Shang Tiantian 
Published: July 2021

PurposeDespite the fact that user participation (UP) has been highlighted as an important aspect in innovation, previous findings on its relationship with service innovation performance (SIP) are inconsistent. This study aims to investigate the relationships among UP, knowledge management capability (KMC) and SIP, especially in the digital age, inspired by the theories of knowledge-based and absorptive capacity.Design/methodology/approachBased on a sample of 252 Chinese e-commerce enterprises, this study adopts a hierarchical regression analysis and bootstrap method to test the theoretical framework and research hypotheses.FindingsUP and KMC have positive effects on SIP, respectively. KMC plays a mediating role in the effect of UP on SIP. Furthermore, the intermediary role of KMC varies in different sub-paths between UP and SIP.Originality/valueFirst, this study provides some explanations for inconsistent arguments on the relationship between UP and service innovation. Second, with the consideration of specific dimensions of UP and SIP, the mediation role of KMC varies in different sub-paths has been recognized, which provides a deeper understanding of the relationship between UP and SIP. Third, this study opens the discussion about how to realize SIP more effectively in the digital age, advancing theoretical and practical developments on service innovation.