bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection and Whole Genome of Japanese Encephalitis Virus Genotype III strains isolated from Indian Pig and Mosquito vector
Authors: Pegu Seema R. , Das Pranab J. , Sonowal Joyshikh , Sengar Gyanendra S. , Deb Rajib , Rajkhowa Swaraj , Choudhury Manjisa , Gulati B. R. , Gupta V. K. 
Published: November 2022

AbstractJapanese encephalitis virus(JEV) are globally prevalent as deadly pathogens in human and animals including pig, horse and cattle. Japanese encephalitis (JE) still remains as an important cause of epidemic encephalitis worldwide and exists in a zoonotic transmission cycle. Assam is one of the highly endemic state for JE in India. In the present study, to understand the epidemiological status of JE circulating in pigs and mosquito particularly in Assam, India, molecular detection of JEV and the complete genome sequencing of the JEV isolates from pig and mosquito were done. The complete genome analysis of two JEV isolates from pig and mosquito were revealed7 and 21 numbers of unique points polymorphism of nucleotide during alignment of the sequences with other available sequences, respectively. Phylogenetic analysis revealed that the isolates of present investigation were belongs to genotype III and closely related with the strains of neighbouring country China. This study represents the transboundary nature of the JEV genotype III circulation and maintained the same genotype through mosquito-swine transmission cycles.
Dieback of stringybark eucalypt forests in the Mount Lofty Ranges
Authors: Guerin Gregory R , Keppel Gunnar , Peters Stefan , Hurren Amelia 
Published: November 2022

AbstractCanopy dieback and concerning rates of tree mortality have been noted in iconic forests of the Mount Lofty Ranges (MLR), South Australia, dominated by the stringybark eucalypt speciesEucalyptus baxteri(Brown Stringybark) andE. obliqua(Messmate Stringybark). The extent and causes of stringybark forest decline are not yet fully understood, prohibiting evidence-based management strategies. Here, we explore the distribution of MLR populations of the two species and their position in climate space relative to eastern populations. We also conducted field assessments to investigate stand health and dieback aetiology, and analysed existing tree monitoring data. Stringybarks in the MLR are disjunct from eastern populations and occupy a more summer-arid niche. The species are also susceptible to summer water stress andPhytophthora. Periods of drought during 2006–2009 and 2018–2019 may have contributed to observed dieback. However, field assessments suggest a complex landscape syndrome that includes borer infestations and fire impacts among other factors, rather than solely hydraulic failure. Messmate Stringybark has suffered widespread but patchy stand collapse. There is no obvious common pattern of collapsed sites with respect to topography or local water availability (e.g., swamps and ridges equally affected), although northern range-edge sites are heavily affected. Brown Stringybark is less affected but has notable collapse sites. We hope these studies establish a springboard for future investigations and more widespread sampling of MLR stringybark forests. Further investigations should include regional surveys of stringybark sites to record spatial and temporal patterns of tree mortality combined with multi- or hyperspectral analysis of remotely sensed imagery and visual inspection of dieback from very high resolution aerial images and ground-truthing. Our findings confirm the susceptibility of stringybark forests in the MLR to ecosystem collapse and highlight the urgent need to understand the causes and aetiology of the observed dieback.
Rational Chemical Design of Molecular Glue Degraders
Authors: Toriki Ethan S. , Papatzimas James W. , Nishikawa Kaila , Dovala Dustin , McGregor Lynn M. , Hesse Matthew J. , McKenna Jeffrey M. , Tallarico John A. , Schirle Markus , Nomura Daniel K. 
Published: November 2022

AbstractTargeted protein degradation with molecular glue degraders has arisen as a powerful therapeutic modality for eliminating classically undruggable disease-causing proteins through proteasome-mediated degradation. However, we currently lack rational chemical design principles for converting protein-targeting ligands into molecular glue degraders. To overcome this challenge, we sought to identify a transposable chemical handle that would convert protein-targeting ligands into molecular degraders of their corresponding targets. Using the CDK4/6 inhibitor Ribociclib as a prototype, we identified a covalent handle that, when appended to the exit vector of Ribociclib, induced the proteasome-mediated degradation of CDK4 in cancer cells. Covalent chemoproteomic profiling of this CDK4 degrader revealed covalent interactions with cysteine 32 of the RING family E3 ubiquitin ligase RNF126. Structural modification of our initial covalent scaffold led to an improved CDK4 degrader with the development of a but-2-ene, 1,4-dione (“fumarate”) handle that showed improved interactions with RNF126. Thereafter, we worked to identify the minimum covalent motif required for interaction with RNF126, which we then transplanted onto chemically related and un-related protein-targeting ligands. This strategy successfully produced molecules which induced the degradation of several proteins across diverse protein classes, including BRD4, BCR-ABL and c-ABL, PDE5, AR and AR-V7, BTK, LRRK2, and SMARCA2. Our study undercovers a design strategy for converting protein-targeting ligands into covalent molecular glue degraders.
ImmuneBuilder: Deep-Learning models for predicting the structures of immune proteins
Authors: Abanades Brennan , Wong Wing Ki , Boyles Fergus , Georges Guy , Bujotzek Alexander , Deane Charlotte M. 
Published: November 2022

AbstractImmune receptor proteins play a key role in the immune system and have shown great promise as biotherapeutics. The structure of these proteins is critical for understanding their antigen binding properties. Here, we present ImmuneBuilder, a set of deep learning models trained to accurately predict the structure of antibodies (ABodyBuilder2), nanobodies (NanoBodyBuilder2) and T-Cell receptors (TCRBuilder2). We show that ImmuneBuilder generates structures with state of the art accuracy while being far faster than AlphaFold2. For example, on a benchmark of 34 recently solved antibodies, ABodyBuilder2 predicts CDR-H3 loops with an RMSD of 2.81Å, a 0.09Å improvement over AlphaFold-Multimer, while being over a hundred times faster. Similar results are also achieved for nanobodies, (NanoBodyBuilder2 predicts CDR-H3 loops with an average RMSD of 2.89Å, a 0.55Å improvement over AlphaFold2) and TCRs. By predicting an ensemble of structures, ImmuneBuilder also gives an error estimate for every residue in its final prediction. ImmuneBuilder is made freely available, both to download (https://github.com/oxpig/ImmuneBuilder) and to use via our webserver (http://opig.stats.ox.ac.uk/webapps/newsabdab/sabpred). We also make available structural models for ~150 thousand non-redundant paired antibody sequences (https://zenodo.org/record/7258553).
Phosphoproteomic profiling highlights CDC42 and CDK2 as key players in the regulation of the TGF-β pathway inALMS1andBBS1knockout models
Authors: Bea-Mascato Brais , Giudice Girolamo , Pinheiro-de-Sousa Iguaracy , Solarat Carlos , Petsalaki Evangelia , Valverde Diana 
Published: November 2022

ABSTRACTBACKGROUNDThe primary cilium is a sensory organelle that extends from the plasma membrane. It plays a vital role in physiological and developmental processes by controlling different signalling pathways such as WNT, Sonic hedgehog (SHh), and transforming growth factor β (TGF-β). Ciliary dysfunction has been related to different pathologies such as Alström (ALMS) or Bardet-Biedl (BBS) syndrome. The leading cause of death in adults with these syndromes is chronic kidney disease (CKD), which is characterised by fibrotic and inflammatory processes often involving the TGF-β pathway.METHODSUsing genomic editing with CRISPR-CAS9 and phosphoproteomics we have studied the TGF-β signalling pathway in knockout (KO) models forALMS1andBBS1genes. We have developed a network diffusion-based analysis pipeline to expand the data initially obtained and to be able to determine which processes were deregulated in TGF-β pathway. Finally, we have analysed protein-protein and kinase-substrate interactions to prioritise candidate genes in the regulation of the TGF-β pathway in ALMS and BBS.RESULTSAnalysis of differentially phosphorylated proteins identified 10 candidate proteins in theALMS1KO model and 41 in theBBS1KO model. After network expansion using a random walk with a restart algorithm, we were able to identify the TGF-β signalling pathway together with other related processes such as endocytosis in the case ofALMS1or the regulation of the extracellular matrix inBBS1. Protein interaction analyses demonstrated the involvement of CDC42 as a central protein in the interactome inALMS1and CDK2 in the case ofBBS1.CONCLUSIONIn conclusion, the depletion ofALMS1andBBS1affects the TGF-β signalling pathway, conditioning the phosphorylation and activation of several proteins, including CDC42 in the case ofALMS1and CDK2 in the case ofBBS1.
A Web/Cloud based Digital Pathology Platform Framework for AI Development and Deployment
Authors: Akkus Zeynettin , Dangott Bryan , Nassar Aziza 
Published: November 2022

AbstractDigitization of glass slides has brought several opportunities with it for computational pathology and artificial intelligence (AI). The application of AI in digital pathology slides shows potential for QA/QC, triaging cases, and assisting pathologists in clinical decision making. We present an extensible and modular web/cloud based digital pathology framework for AI development and deployment. The proposed platform supports collaborative multi-user and multi-device annotation, remote slide access, and remote telepathology or teleconsultation tasks.
Microplastics are present in women’s and cows’ follicular fluid and polystyrene microplastics compromise bovine oocyte functionin vitro
Authors: Grechi Nicole , Franko Roksan , Rajaraman Roshini , Stöckl Jan B. , Trapphoff Tom , Dieterle Stefan , Fröhlich Thomas , Noonan Michael J. , de A. M. M. Ferraz Marcia 
Published: November 2022

AbstractThe past several decades have seen alarming declines in the reproductive health of humans, animals and plants. While humans have introduced numerous pollutants that can impair reproductive systems (such as well-documented endocrine disruptors), the potential for microplastics (MPs) to be contributing to the widespread declines in fertility is particularly noteworthy. Over the same timespan that declines in fertility began to be documented, there has been a correlated shift towards a “throw-away society” that is characterised by the excessive consumption of single-use plastic products and a concomitant accumulation of MPs pollution. Studies are showing that MPs can impair fertility, but data have been limited to rodents that were force-fed hundreds of thousands of times more plastics than they would be exposed in the environment. As a first step to linkin vitrohealth effects within vivoenvironmental exposure, we quantified microplastics in the follicular fluid of women and domestic cows. We found that the concentrations of polystyrene microplastics that naturally occurred in follicular fluid were sufficient to compromise the maturation of bovine oocytesin vitro. Collectively, these findings demonstrate that microplastics may also be contributing to the widespread declines in fertility that have been occurring over recent Anthropocene decades.
Discovery of aphid-transmitted Rice tiller inhibition virus from native plants through metagenomic sequencing
Authors: Yan Wenkai , Zhu Yu , Liu Wencheng , Zou Chengwu , Jia Bei , Chen Zhong-Qi , Han Yanhong , Wu Jianguo , Yang Dong-lei , Chen Baoshan , Li Rongbai , Ding Shou-Wei , Wu Qingfa , Guo Zhongxin 
Published: November 2022

AbstractA major threat to rice production is the disease epidemics caused by insect-borne viruses that emerge and re-emerge with undefined origins. It is well known that some human viruses have zoonotic origins from wild animals. However, it remains unknown whether native plants host new endemic viruses with spillover potential to rice (Oryza sativa) as emerging pathogens. Here, we discovered rice tiller inhibition virus (RTIV), a novel RNA virus species, from colonies of Asian wild rice (O. rufipogon) in a genetic reserve by metagenomic sequencing. We identified the specific aphid vector to transmit RTIV and found RTIV would cause low-tillering disease in rice cultivar after transmission. We further demonstrated that an infectious molecular clone of RTIV initiated systemic infection and causes low-tillering disease in an elite rice variety after Agrobacterium-mediated inoculation or stable plant transformation, and RTIV can also be transmitted from transgenic rice plant through its aphid vector to cause disease. Finally, global transcriptome analysis indicated that RTIV may disturb defense and tillering pathway to cause low tillering disease in rice cultivar. Thus, our results show that new rice viral pathogens can emerge from native habitats, and RTIV, a rare aphid-transmitted rice viral pathogen from native wild rice, can threaten the production of rice cultivar after spillover.
Integrated transcriptome and lineage analyses reveal novel catecholaminergic cardiomyocytes contributing to the cardiac conduction system in murine heart
Authors: Sun Tianyi , Grassam-Rowe Alexander , Pu Zhaoli , Ren Huiying , An Yanru , Guo Xinyu , Hu Wei , Liu Ying , Li Yangpeng , Liu Zhu , Kou Kun , Ou Xianhong , Chen Tangting , Fan Xuehui , Liu Yangyang , Shu Tu , He Yu , Ren Yue , Chen Ao , Shang Zhouchun , Xia Zhidao , Miquerol Lucile , Smart Nicola , Zhang Henggui , Tan Xiaoqiu , Shou Weinian , Lei Ming 
Published: November 2022

SummaryCardiac conduction system (CCS) morphogenesis is essential for correct heart function yet is incompletely understood. Here we established the transcriptional landscape of cell types populating the developing heart by integrating single-cell RNA sequencing and spatial enhanced resolution omics-sequencing (Stereo-seq). Stereo-seq provided a spatiotemporal transcriptomic cell fate map of the murine heart with a panoramic field of view and in situ cellular resolution of the CCS. This led to the identification of a previously unrecognized cardiomyocyte population expressing dopamine beta-hydroxylase (Dbh+-CMs), which is closely associated with the CCS in transcriptomic analyses. To confirm this finding, genetic fate mapping by usingDbhCre/Rosa26-tdTomato reporter mouse line was performed with Stereo-seq, RNAscope, and immunohistology. We revealed thatDbh+-derived CMs first emerged in the sinus venosus at E12.5, then populated the atrial and ventricular CCS components at E14.5, with increasing abundance towards perinatal stages. Further tracing by usingDbhCFPreporter andDbhCreERT/Rosa26-tdTomato inducible reporter, we confirmed thatDbh+-CMs are mostly abundant in the AVN and ventricular CCS and this persists in the adult heart. By usingDbhCre/Rosa26-tdTomato/Cx40-eGFP compound reporter line, we validated a clear co-localization of tdTomato and eGFP signals in both left and right ventricular Purkinje fibre networks. Finally, electrophysiological optogenetic study using cell-type specific Channelrhodopsin2 (ChR2) expression further elucidated thatDbh+-derived CMs form a functional part of the ventricular CCS and display similar photostimulation-induced electrophysiological characteristics to Cx40CreERT/ChR2-tdTomato CCS components. Thus, by utilizing advanced transcriptomic, mouse genetic, and optogenetic functional analyses, our study provides new insights into mammalian CCS development and heterogeneity by revealing novelDbh+-CMs.HighlightsStereo-seq provided a spatiotemporal transcriptomic cell fate map of the murine heart with a panoramic field of view and in situ cellular resolution of the CCS.Established the transcriptional landscape of cell types populating the developing murine heart.Revealed previously unreported catecholaminergic cardiomyocyte populations contributing to the developing and mature murine cardiac conduction system.
pHAPE: a plasmid for production of DNA size marker ladders for gel electrophoresis
Authors: Allen Angel G , Barthelson Karissa , Lardelli Michael 
Published: November 2022

AbstractDNA size markers (also known as “molecular weight markers” or “DNA ladders”) are an essential tool when using gel electrophoresis to identify and purify nucleic acids. However, the cost of these DNA ladders is not insignificant and, over time, impinges on the funds available for research and training in molecular biology. Here, we describe a method for the generation of “pHAPE”, a plasmid from which a variety of DNA ladders can be generated via simple restriction enzyme digestions. The pHAPE plasmid can be generated by mutagenesis of the commonly used pBluescript II SK+ phagemid followed by insertion of a custom 7,141 bp sequence (made up of three smaller fragments). Our use of pHAPE allows us some small relief from the ever-rising costs of performing molecular biology experiments (“Don’t worry, pHAPE”).
Rapid assessment of susceptibility of bacteria and erythrocytes to antimicrobial peptides by single-cell impedance cytometry
Authors: Troiano Cassandra , De Ninno Adele , Casciaro Bruno , Riccitelli Francesco , Park Yoonkyung , Massoud Renato , Mangoni Maria Luisa , Bisegna Paolo , Stella Lorenzo , Caselli Federica 
Published: November 2022

AbstractAntimicrobial peptides (AMPs) represent a promising class of compounds to fight antibiotic-resistant infections. In most cases, they kill bacteria by making their membrane permeable and therefore exhibit low propensity to induce bacterial resistance. In addition, they are often selective, killing bacteria at concentrations lower than those at which they are toxic to the host. However, clinical applications of AMPs are hindered by a limited understanding of their interactions with bacteria and human cells. Standard susceptibility testing methods are based on the analysis of the growth of a bacterial population and therefore require several hours. Moreover, different assays are required to assess the toxicity to host cells. In this work, we propose the use of microfluidic impedance cytometry to explore the action of AMPs on both bacteria and host cells, in a rapid manner and with single-cell resolution. We show that the electrical signatures ofBacillus megaterium (B. megaterium)cells and human red blood cells (RBCs) reflect the action of a representative antimicrobial peptide, DNS-PMAP23. In particular, the impedance phase at high frequency (e.g., 11 or 20 MHz) is a reliable label-free metric for monitoring DNS-PMAP23 bactericidal activity and toxicity to RBCs. The impedance-based characterization is validated by comparison with standard antibacterial activity assays and absorbance-based hemolytic activity assays. Furthermore, we demonstrate the applicability of the technique to a mixed sample ofB. megateriumcells and RBCs, which paves the way to study AMP selectivity for bacterial versus eukaryotic cells in presence of both cell types.
Energetic costs of bill heat exchange demonstrate contributions to thermoregulation at high temperatures in toco toucans (Ramphastos toco)
Authors: Chaves Jussara N. , Tattersall Glenn J. , Andrade Denis V. 
Published: November 2022

ABSTRACTBody temperature regulation in the face of changes in ambient temperature and/or in metabolic heat production involves adjustments in heat exchange rates between the animal and the environment. One of those mechanisms include the modulation of the surface temperature of specific areas of the body through vasomotor adjustment and blood flow control, to change the thermal conductance of this region, thereby promoting dissipation or conservation of body heat. In homeotherms, this thermoregulatory adjustment is essential for the maintenance of body temperature over a moderate temperature range, known as the thermal neutral zone (TNZ), without increasing metabolic rate (MR). Thermal windows are poorly insulated body regions and highly vascularized that are particularly efficient for heat dissipation through that mechanism. The bill of the toco toucan (Ramphastos toco) has been described as a highly efficient thermal window and hypothesized to assist in the thermal homeostasis of this bird. Herein, we directly evaluated the contribution of heat exchange through the bill of the toco toucan and role of the bill in the delimitation of the TNZ. To do this, we measured metabolic rate, via oxygen consumption, over a range of ambient temperature from 0 to 35°C (every 5°C). MR measurements were made in birds with the bill intact (control group) and with the bill artificially insulated (experimental group). The limits of the TNZ, 10.9-25.0°C for the control group and 10.8-24.1°C for the experimental group, did not differ between the treatments. MR differed among treatments only at elevated temperatures (30 and 35°C), reaching values of 0.97 ml O2·g-1·h-1·°C-1(± 0.06) for the control group and 1.20 ml O2·g-1·h-1·°C-1(± 0.07) for the experimental group at 35°C. These results indicate that while heat dissipation through the bill does not contribute significantly to widening of the TNZ, it may well be critically important in assisting body temperature regulation at higher temperatures extending above the upper limit of the TNZ. We estimate that the contribution of the bill to total heat exchange approaches 31% of basal metabolic heat production, providing evidence of the substantial role of peripheral heat exchange and linking the role of appendage size as a key factor in the evolution of thermoregulatory responses in endotherms.
Lipidomic alterations in the cerebral cortex and white matter in sporadic Alzheimer’s disease
Authors: Obis Elia , Sol Joaquim , Andres-Benito Pol , Martín-Gari Meritxell , Mota-Martorell Natàlia , Galo-Licona José Daniel , Piñol-Ripoll Gerard , Portero-Otin Manuel , Ferrer Isidro , Jové Mariona , Pamplona Reinald 
Published: November 2022

AbstractAimsNon-targeted lipidomics analysis was conducted in post-mortem human frontal cortex area 8 (GM) and white matter of the frontal lobecentrum semi-ovale(WM) to identify lipidomes in middle-aged individuals with no neurofibrillary tangles and senile plaques, and cases at progressive stages of sporadic Alzheimer’s disease (sAD).MethodsLipidomic analysis using an LC-MS/MS platform was carried out in selected cases with suitable post-mortem lacking co-morbidities and concomitant brain pathologies. Complementary data were obtained using RT-qPCR and immunohistochemistry.ResultsThe WM shows an adaptive lipid phenotype resistant to lipid peroxidation, characterized by a lower fatty acid unsaturation, peroxidizability index, and higher ether lipid content than the GM. Changes in the lipidomic profile more marked in the WM than in GM occur in AD with disease progression. WM alterations are characterized by a decline in the content of branched fatty acid esters of hydroxy fatty acids (FAHFA), diacylglycerols (DG), triacylglycerols (TG), glycerophospholipids (GP) (especially ether lipids), and sphingolipids (especially sulfatides, ceramides, and glycosphingolipids). The GM acquires a fatty acid profile prone to peroxidation in sAD, while WM reinforces its peroxidation-resistant trait. Transcriptomic data point to additional defects of peroxisomal function.ConclusionsFour functional categories are associated with the different lipid classes affected in sAD: membrane structural composition, bioenergetics, antioxidant protection, and bioactive lipids, with deleterious consequences affecting both neurons and glial cells favoring disease progression.