bluuebunny/crossref_metadata_2025_split huggingface dataset:
Child abuse associates with increased recruitment of perineuronal nets in the ventromedial prefrontal cortex: a possible implication of oligodendrocyte progenitor cells
Authors: Tanti Arnaud , Belliveau Claudia , Nagy Corina , Maitra Malosree , Denux Fanny , Perlman Kelly , Chen Frank , Mpai Refilwe , Canonne Candice , Théberge Stéphanie , McFarquhar Ashley , Davoli Maria Antonietta , Belzung Catherine , Turecki Gustavo , Mechawar Naguib 
Published: October 2020

AbstractChild abuse (CA) is a strong predictor of psychopathologies and suicide, altering normal trajectories of brain development in areas closely linked to emotional responses such as the prefrontal cortex (PFC). Yet, the cellular underpinnings of these enduring effects are unclear. Childhood and adolescence are marked by the protracted formation of perineuronal nets (PNNs), which orchestrate the closure of developmental windows of cortical plasticity by regulating the functional integration of parvalbumin interneurons (PV) into neuronal circuits. Using well-characterized post-mortem brain samples, we show that a history of CA is specifically associated with increased densities and morphological complexity of WFL-labeled PNNs in the ventromedial PFC (BA11/12), possibly suggesting increased recruitment and maturation of PNNs. Through single-nucleus sequencing and fluorescent in-situ hybridization, we found that the expression of canonical components of PNNs is enriched in oligodendrocyte progenitor cells (OPCs), and that they are upregulated in CA victims. These correlational findings suggest that early-life adversity may lead to persistent patterns of maladaptive behaviors by reducing the neuroplasticity of cortical circuits through the enhancement of developmental OPC-mediated PNN formation.
Pore constrictions in intervessel pit membranes reduce the risk of embolism spreading in angiosperm xylem
Authors: Kaack Lucian , Weber Matthias , Isasa Emilie , Karimi Zohreh , Li Shan , Pereira Luciano , Trabi Christophe L. , Zhang Ya , Schenk H. Jochen , Schuldt Bernhard , Schmidt Volker , Jansen Steven 
Published: October 2020

SummaryEmbolism spreading in angiosperm xylem occurs via mesoporous pit membranes between vessels. Here, we investigate how the size of pore constrictions in pit membranes is related to pit membrane thickness and embolism resistance.In three models, pit membranes are modelled as multiple layers to investigate how pit membrane thickness and the number of intervessel pits per vessel determine pore constriction sizes, the probability of encountering large pores, and air-seeding. These estimations were complemented by measurements of pit membrane thickness, embolism resistance, and number of intervessel pits per vessel (n= 31, 31, and 20 species, respectively).Constriction sizes in pores decreased with increasing pit membrane thickness, which agreed with the measured relationship between pit membrane thickness and embolism resistance. The number of pits per vessel affected constriction size and embolism resistance much less than pit membrane thickness. A strong relationship between estimated air-seeding pressures and measured embolism resistance was observed.Pore constrictions provide a mechanistic explanation why pit membrane thickness determines embolism resistance, and suggest that hydraulic safety can be uncoupled from hydraulic efficiency. Although embolism spreading remains puzzling and encompasses more than pore constriction sizes, angiosperms are unlikely to have leaky pit membranes, which enables tensile transport of water.
Structural basis of SARS-CoV-2 polymerase inhibition by Favipiravir
Authors: Peng Qi , Peng Ruchao , Yuan Bin , Wang Min , Zhao Jingru , Fu Lifeng , Qi Jianxun , Shi Yi 
Published: October 2020

AbstractThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into an unprecedented global pandemic. Nucleoside analogues, such as Remdesivir and Favipiravir, can serve as the first-line broad-spectrum antiviral drugs against the newly emerging viral diseases. Recent clinical trials of these two drugs for SARS-CoV-2 treatment revealed antiviral efficacies as well as side effects with different extents1–4. As a pyrazine derivative, Favipiravir could be incorporated into the viral RNA products by mimicking both adenine and guanine nucleotides, which may further lead to mutations in progeny RNA copies due to the non-conserved base-pairing capacity5. Here, we determined the cryo-EM structure of Favipiravir bound to the replicating polymerase complex of SARS-CoV-2 in the pre-catalytic state. This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase, and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues which may explain its capacity for mimicking both adenine and guanine nucleotides. These findings shed lights on the mechanism of coronavirus polymerase catalysis and provide a rational basis for developing antiviral drugs to combat the SARS-CoV-2 pandemic.
EVALUATION OF ANTI-BACTERIAL AND ANTHELMINTIC ACTIVITIES OF BARK OF PLANTCASSIA FISTULALinn
Authors: Nayabaniya Anant , Aryal Samyam , Dahal Bibek , Khanal Hemanta , Gupta Anil K. 
Published: October 2020

AbstractThis study deals with phytochemical screening and evaluation of anti-bacterial and anthelmintic activities of the bark extracts ofCassia fistulaL. The extraction with different solvents - methanol, acetone, distilled water - had been carried out. The anti-bacterial assay was done against two gram +ve and two gram −ve bacteria by agar cup diffusion method. The anthelmintic activity was done onPheretima posthuma(earthworm) by recording the paralyzing and death time under different concentrations. Methanolic extract showed the maximum activity on both fronts be it anti-bacterial or anthelmintic. The extract was effective only against gram +ve bacteria. AmongStaphylococcus aureusandStreptococci faecalis, the former was more susceptible. The activity against gram −ve bacteria was not found. In case of anthelmintic activity, the concentration of 50 mg/ml was effective and near to the paralyzing and death time as recorded for the 10 mg/ml concentration of the standard Albendazole. However, aqueous extract was more effective than the acetone extract.
Prioritization of prostate cancer to immune checkpoint therapy by ranking tumors along IFN-γ axis and identification of immune resistance mechanisms
Authors: Reva Boris , Omelchenko Tatiana , Calinawan Anna , Nair Sujit , Schadt Eric , Tewari Ash 
Published: October 2020

AbstractWe propose priotirization of prostate cancer patients to PD-L1 checkpoint therapy by assessing activity of IFN-γ/PD-L1 signaling in tumor from transcriptional profile. To this end, we introduced a new approach for inferring pathway activity and suppression (IPAS) by assessing significance of positioning pathway’s genes expression levels at top (activation) or bottom (suppression) in gene expression profile of a given tumor. By ordering tumors along IFN-γ/PD-L1 axis, we determined distinct “IFN-γ-depleted” and “IFN-γ-enriched” immune subtypes, genes involved in immune evasion and potential targets for combination therapy. Using IPAS scoring method, we proposed biomarker panels for accurate ranking tumors along IFN-γ/PD-L1 axis.
Real-Time Observation of Structure and Dynamics during the Liquid-to-Solid Transition of FUS LC
Authors: Berkeley Raymond F. , Kashefi Maryam , Debelouchina Galia T. 
Published: October 2020

AbstractMany of the proteins found in pathological protein fibrils also exhibit tendencies for liquid-liquid phase separation (LLPS) bothin vitroand in cells. The mechanisms underlying the connection between these phase transitions have been challenging to study due to the heterogeneous and dynamic nature of the states formed during the maturation of LLPS protein droplets into gels and solid aggregates. Here, we interrogate the liquid-to-solid transition of the low complexity domain of the RNA binding protein FUS (FUS LC), which has been shown to adopt LLPS, gel-like, and amyloid states. We employ magic-angle spinning (MAS) NMR spectroscopy which has allowed us to follow these transitions in real time and with residue specific resolution. We observe the development of β-sheet structure through the maturation process and show that the final state of FUS LC fibrils produced through LLPS is distinct from that grown from fibrillar seeds. We also apply our methodology to FUS LC G156E, a clinically relevant FUS mutant that exhibits accelerated fibrillization rates. We observe significant changes in dynamics during the transformation of the FUS LC G156E construct and begin to unravel the sequence specific contributions to this phenomenon with computational studies of the phase separated state of FUS LC and FUS LC G156E.SignificanceThe presence of protein aggregates and plaques in the brain is a common pathological sign of neurodegenerative disease. Recent work has revealed that many of the proteins found in these aggregates can also form liquid-liquid droplets and gels. While the interconversion from one state to another can have vast implications for cell function and disease, the molecular mechanisms that underlie these processes are not well understood. Here, we combine MAS NMR spectroscopy with other biophysical and computational tools to follow the transitions of the stress response protein FUS. This approach has allowed us to observe real-time changes in structure and dynamics as the protein undergoes these transitions, and to reveal the intricate effects of disease-relevant mutations on the transformation process.
Differences in cofactor, oxygen and sulfur requirements influence niche adaptation in deep-sea vesicomyid clam symbioses
Authors: Breusing Corinna , Perez Maёva , Beinart Roxanne A. , Young C. Robert 
Published: October 2020

AbstractVertical transmission of bacterial endosymbionts is accompanied by virtually irreversible gene loss that can provide insights into adaptation to divergent ecological niches. While patterns of genome reduction have been well described in some terrestrial symbioses, they are less understood in marine systems where vertical transmission is relatively rare. The association between deep-sea vesicomyid clams and chemosynthetic Gammaproteobacteria is one example of maternally inherited symbioses in the ocean. Differences in nitrogen and sulfur physiology between the two dominant symbiont groups,Ca.Ruthia andCa.Vesicomyosocius, have been hypothesized to influence niche exploitation, which likely affects gene content evolution in these symbionts. However, genomic data are currently limited to confirm this assumption. In the present study we sequenced and compared 11 vesicomyid symbiont genomes with existing assemblies forCa. Vesicomyosocius okutanii andCa. Ruthia magnifica. Our analyses indicate that the two vesicomyid symbiont groups have a common core genome related to chemosynthetic metabolism, but differ in their potential for nitrate respiration and flexibility to environmental sulfide concentrations. Moreover,Ca. Vesicomyosocius andCa. Ruthia have different enzymatic requirements for cobalamin and nickel and show contrasting capacities to acquire foreign genetic material. Tests for site-specific positive selection in metabolic candidate genes imply that the observed physiological differences are adaptive and thus likely correspond to ecological niches available to each symbiont group. These findings highlight the role of niche differentiation in creating divergent paths of reductive genome evolution in vertically transmitted symbionts.
Constructing Gene Regulatory Networks using Epigenetic Data
Authors: Sonawane Abhijeet Rajendra , DeMeo Dawn L. , Quackenbush John , Glass Kimberly 
Published: October 2020

AbstractThe biological processes that drive cellular function can be represented by a complex network of interactions between regulators (transcription factors) and their targets (genes). A cell’s epigenetic state plays an important role in mediating these interactions, primarily by influencing chromatin accessibility. However, effectively leveraging epigenetic information when constructing regulatory networks remains a challenge. We developed SPIDER, which incorporates epigenetic information (DNase-Seq) into a message passing framework in order to estimate gene regulatory networks. We validated SPIDER’s predictions using ChlP-Seq data from ENCODE and found that SPIDER networks were more accurate than other publicly available, epigenetically informed regulatory networks as well as networks based on methods that leverage epigenetic data to predict transcription factor binding sites. SPIDER was also able to improve the detection of cell line specific regulatory interactions. Notably, SPIDER can recover ChlP-seq verified transcription factor binding events in the regulatory regions of genes that do not have a corresponding sequence motif. Constructing biologically interpretable, epigenetically informed networks using SPIDER will allow us to better understand gene regulation as well as aid in the identification of cell-specific drivers and biomarkers of cellular phenotypes.
Cyclic-di-GMP induces STING-dependent ILC2 to ILC1 shift during innate type 2 lung inflammation
Authors: Cavagnero Kellen J. , Badrani Jana H. , Naji Luay H. , Amadeo Michael B. , Leng Anthea S. , Lacasa Lee Diego , Strohm Allyssa N. , Doherty Taylor A. 
Published: October 2020

ABSTRACTType 2 inflammation is found in most forms of asthma, which may co-exist with recurrent viral infections, bacterial colonization, and host cell death. These processes drive the accumulation of intracellular cyclic-di-nucleotides such as cyclic-di-GMP (CDG). Group 2 innate lymphoid cells (ILC2s) are critical drivers of type 2 lung inflammation during fungal allergen exposure in mice; however, it is unclear how CDG regulates lung ILC responses during lung inflammation. Here, we show that CDG induced early airway type 1 interferon (IFN) production and dramatically suppressed both lung proliferating CD127+ST2+ ILC2s andAlternaria- and IL-33-induced lung inflammation. Further, transcriptomic analysis of CD127−ST2− Thy1.2+ ILCs, which were expanded and activated by CDG, revealed an ILC1 signature. CDG administration led to accumulation of IFNγ+ and T-bet+ ILC1s, as well as neutrophilia, independent of IL-18R, IL-12, and STAT6 but dependent on stimulator of interferon genes (STING) and partially dependent on type 1 IFN signaling. Thus, CDG potently suppresses ILC2-driven lung inflammation and promotes ILC1 responses. These results suggest potential therapeutic modulation of STING to suppress type 2 inflammation and/or increase anti-viral responses during respiratory infections.
Markov State Models and NMR Uncover an Overlooked Allosteric Loop in p53
Authors: Barros Emilia P. , Demir Özlem , Soto Jenaro , Cocco Melanie J. , Amaro Rommie E. 
Published: October 2020

ABSTRACTThe tumor suppressor p53 is the most frequently mutated gene in human cancer, and thus reactivation of mutated p53 is a promising avenue for cancer therapy. Analysis of wildtype p53 and the Y220C cancer mutant long-timescale molecular dynamics simulations with Markov state models and validation by NMR relaxation studies has uncovered the involvement of loop L6 in the slowest motions of the protein. Due to its distant location from the DNA-binding surface, the conformational dynamics of this loop has so far remained largely unexplored. We observe mutation-induced stabilization of alternate L6 conformations, distinct from all experimentally-determined structures, in which the loop is both extended and located further away from the DNA-interacting surface. Additionally, the effect of the L6-adjacent Y220C mutation on the conformational landscape of the functionally-important loop L1 suggests an allosteric role to this dynamic loop and the inactivation mechanism of the mutation. Finally, the simulations reveal a novel Y220C cryptic pocket that can be targeted for p53 rescue efforts. Our approach exemplifies the power of the MSM methodology for uncovering intrinsic dynamic and kinetic differences among distinct protein ensembles, such as for the investigation of mutation effects on protein function.
Septate junction proteins are required for egg elongation and border cell migration during oogenesis in Drosophila
Authors: Alhadyian Haifa , Shoaib Dania , Ward Robert E. 
Published: October 2020

AbstractProtein components of the invertebrate occluding junction - known as the septate junction (SJ) - are required for morphogenetic developmental events during embryogenesis inDrosophila melanogaster. In order to determine whether SJ proteins are similarly required for morphogenesis during other developmental stages, we investigated the localization and requirement of four representative SJ proteins during oogenesis: Contactin, Macroglobulin complement-related, Neurexin IV, and Coracle. A number of morphogenetic processes occur during oogenesis, including egg elongation, formation of dorsal appendages, and border cell migration. We found that all four SJ proteins are expressed in egg chambers throughout oogenesis, with the highest and most sustained levels in the follicular epithelium (FE). In the FE, SJ proteins localize along the lateral membrane during early and mid-oogenesis, but become enriched in an apical-lateral domain (the presumptive SJ) by stage 10b. SJ protein relocalization requires the expression of other SJ proteins, as well as rab5 and rab11 in a manner similar to SJ biogenesis in the embryo. Knocking down the expression of these SJ proteins in follicle cells throughout oogenesis results in egg elongation defects and abnormal dorsal appendages. Similarly, reducing the expression of SJ genes in the border cell cluster results in border cell migration defects. Together, these results demonstrate an essential requirement for SJ genes in morphogenesis during oogenesis, and suggests that SJ proteins may have conserved functions in epithelial morphogenesis across developmental stages.Article SummarySeptate junction (SJ) proteins are essential for forming an occluding junction in epithelial tissues ofDrosophila melanogaster, and also for morphogenetic events that occur prior to the formation of the junction during embryogenesis. Here we show that SJ proteins are expressed in the follicular epithelium of egg chambers during oogenesis and are required for morphogenetic events including egg elongation, dorsal appendages formation, and border cell migration. Additionally, the formation of SJs during oogenesis is similar to that in embryonic epithelia.
Metabolic contributions of an alphaproteobacterial endosymbiont in the apicomplexanCardiosporidium cionae
Authors: Hunter Elizabeth Sage , Paight Christopher J , Lane Christopher E 
Published: October 2020

AbstractApicomplexa is a diverse protistan phylum composed almost exclusively of metazoan-infecting parasites, including the causative agents of malaria, cryptosporidiosis, and toxoplasmosis. A single apicomplexan genus,Nephromyces, was described in 2010 as a mutualist partner to its tunicate host. Here we present genomic and transcriptomic data from the parasitic sister species to this mutualist,Cardiosporidium cionae,and its associated bacterial endosymbiont.Cardiosporidium cionaeandNephromycesboth infect tunicate hosts, localize to similar organs within these hosts, and maintain bacterial endosymbionts. Though many other protists are known to harbor bacterial endosymbionts, these associations are completely unknown in Apicomplexa outside of the Nephromycidae clade. Our data indicate that a vertically transmittedα-proteobacteria has been retained in each lineage sinceNephromycesandCardiosporidiumdiverged. Thisα-proteobacterial endosymbiont has highly reduced metabolic capabilities, but contributes the essential amino acid lysine, and essential cofactor lipoic acid toC. cionae. This partnership likely reduces resource competition with the tunicate host. However, our data indicate that the contribution of the singleα-proteobacterial endosymbiont inC. cionaeis minimal compared to the three taxa of endosymbionts present in theNephromycessystem, and is a potential explanation for the virulence disparity between these lineages.
Influence of spin orbit splitting and satellite transitions on nickel soft X-ray optical properties near its L
2,3 absorption edge region
Authors: Kiranjot  , Modi Mohammed H. , Gupta Raj Kumar , Sinha Mangalika , Yadav Praveen Kumar 
Published: October 2020

Transition elements exhibit strong correlations and configuration interactions between core and valence excited states, which give rise to different excitations inside materials. Nickel exhibits satellite features in its emission and absorption spectra. Effects of such transitions on the optical constants of nickel have not been reported earlier and the available database of Henke et al. does not represent such fine features. In this study, the optical behaviour of ion beam sputter deposited Ni thin film near the L
2,3-edge region is investigated using reflection spectroscopy techniques, and distinct signatures of various transitions are observed. The soft X-ray reflectivity measurements in the 500–1500 eV photon energy region are performed using the soft X-ray reflectivity beamline at the Indus-2 synchrotron radiation source. Kramers–Kronig analysis of the measured reflectivity data exhibit features corresponding to spin orbital splitting and satellite transitions in the real and imaginary part of the refractive index (refraction and absorption spectra). Details of fine features observed in the optical spectra are discussed. To the best of our knowledge, this is the first study reporting fine features in the measured optical spectra of Ni near its L
2,3-edge region.
Energy and exergy prices of the jet kerosene fuel with carbon emission equivalents for an aircraft used in the air transport sector in Turkey
Authors: Yildiz Ibrahim , Caliskan Hakan 
Published: October 2020

Purpose
The purpose of this study is to evaluate the energy and exergy prices and carbon emission equivalents of the jet kerosene (Jet A-1) fuel considering 12 months data for an air craft used in the air transport sector in Turkey.

Design/methodology/approach
In the selection of the energy resources, one of the most important factors besides the need is the price of the energy resources. To use and save the energy resources efficiently, the prices should be evaluated in terms of exergy too. In this context, the exergy prices and carbon emission equivalents of the jet kerosene fuel have been examined.

Findings
According to analysis results, after January 2020, a steady decline in energy prices has been obtained until April 2020. In this regard, directly proportional changes have been obtained in exergy prices. The minimum exergy price of the fuel is calculated as 74.36 US cents/kWh for April 2020, while the maximum exergy price of the fuel is calculated as 150.02 US cents/kWh for September 2019. The minimum exergy price based carbon emission equivalents for the jet kerosene fuel is determined as 1,099.98 US cents/kg for April 2020, while the maximum exergy price based carbon emission equivalents for the jet kerosene fuel is found to be 2,219.29 US cents/kg for September 2019.

Originality/value
The new contribution has been made to the open literature by examining the energy and exergy prices of the jet kerosene fuel. In addition, the carbon emission equivalents of the jet kerosene fuel have been determined not only energy but also exergy methods.