bluuebunny/crossref_metadata_2025_split huggingface dataset:
NEAT (NicotinE As Treatment) Trial: Protocol of a randomised controlled trial of vaporised nicotine products compared with nicotine replacement therapy following discharge from residential withdrawal services
Authors: Bonevski B , Rich JL , Skelton E , Garfield J , Baker AL , Segan C , Gartner C , Walker N , Borland R , Daglish M , Dunlop A , Oldmeadow C , Bauld L , Bullen C , Ezard N , McCrohan R , Jacka D , White S , Lubman DI , Manning V 
Published: May 2022

ABSTRACTBackgroundTobacco smoking rates in alcohol and other drug (AOD) treatment settings is much higher than in the general Australian population. As a result, people seeking treatment for AOD use experience a greater tobacco-related burden of illness. Attempts to reduce smoking rates in AOD treatment consumers have failed to identify smoking cessation strategies with long term effectiveness. The primary aim of this study is to examine the effectiveness of nicotine vaporised products (NVPs) or nicotine replacement therapy (NRT)on self-reported 6 months continuous abstinence at the 9-month follow-up (6 months following end-of 12 weeks of nicotine treatment) for people leaving smoke-free residential withdrawal treatment. Both groups will also receive Quitline telephone counselling. Secondary outcomes and process measures will also be collected.MethodsA two-arm, single-blinded, parallel-group randomised trial with a 6-month post-intervention follow-up (9 months following baseline) will be conducted. The setting is five residential and inpatient government-funded AOD withdrawal units across three cities in three states of Australia (New South Wales, Queensland, Victoria). Participants will be service users aged 18 years or over who smoked at least 10 cigarettes per day, interested in quitting in the next 30 days and have capacity to give informed consent. Research assistants will recruit participants during intake, who then complete a baseline survey, will be randomised to a condition, and receive their first Quitline call during AOD treatment. At discharge, all participants receive a discharge pack containing either NVPs or NRT, depending on condition allocation.DiscussionThis is the first study we know of that will be testing intervening with a tobacco smoking cessation approach during the transition phase from AOD treatment to community. From a public health perspective, this approach has the potential to have tremendous reach into a priority population for smoking cessation.Trial registrationAustralian and New Zealand Clinical Trials Registry (ACTRN12619001787178)
CITE-Viz: Replicating the Interactive Flow Cytometry Workflow in CITE-Seq
Authors: Kong Garth L. , Nguyen Thai T. , Rosales Wesley K. , Panikar Anjali D. , Cheney John H. W. , Curtiss Brittany M. , Carratt Sarah A. , Braun Theodore P. , Maxson Julia E. 
Published: May 2022

AbstractSummaryThe rapid advancement of new genomic sequencing technology has enabled the development of multi-omic single-cell sequencing assays. These assays profile multiple modalities in the same cell and can often yield new insights not revealed with a single modality. For example, CITE-Seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) simultaneously profiles the single-cell RNA transcriptome and the surface protein expression. The extra dimension of surface protein markers can be used to further identify cell clusters – an essential step for downstream analyses and interpretation. Additionally, multi-dimensional datasets like CITE-Seq require nuanced visualization methods to accurately assess the data. To facilitate cell cluster classification and visualization in CITE-Seq, we developed CITE-Viz. CITE-Viz is a single-cell visualization platform with a custom module that replicates the interactive flow-cytometry gating workflow. With CITE-Viz, users can investigate CITE-Seq specific quality control (QC) metrics, view multi-omic co-expression feature plots, and classify cell clusters by iteratively gating on the abundance of cell surface markers. CITE-Viz was developed to make multi-modal single-cell analysis accessible to a wide variety of biologists, with the aim to discover new insights into their data and to facilitate novel hypothesis generation.Availability and ImplementationCITE-Viz installation and usage instructions can be found in the GitHub repository https://github.com/maxsonBraunLab/CITE-VizContactmaxsonj@ohsu.eduSupplementary InformationDown-sampled peripheral blood mononuclear dataset (Hao et al. 2021): https://bit.ly/3vxbhfW
Shelf-Life Specific Moisture Variation in Chitosan of Genus Fenneropenaeus Distributed Along Arabian Sea, India
Authors: R S Sreelekshmi , Alex Lincy , Jose Jean J 
Published: May 2022

AbstractChitosan is a characteristic polysaccharide, naturally extracted from the crustacean’s shells. The stability and shelf-life of chitosan are affected by a few parameters, basically the moisture content. In this study, three species of shrimps such as Indian white shrimp (Fenneropenaeus indicus), banana shrimp (F. merguensis), and tiger prawn (F. monodon) were utilized for the extraction of chitosan. The extraction strategy included the method of demineralization, deproteinization, and deacetylation. Later the yield and moisture of chitosan were examined from three diverse species. The yield of shell waste ranged between 46% to 50% (on moist weight premise) and the chitosan was between 18.0 to 20.2%. Moisture content always plays a critical part in chitosan shelf life and stability and was between 5.2% to 6.8 %.
Adaptive Immune Landscape of T-Cell Mediated Rejection of Human Kidney Allografts
Authors: Mueller Franco B. , Yang Hua , Li Carol , Snopkowski Catherine , Dadhania Darshana M. , Xiang Jenny Z. , Salvatore Steven , Seshan Surya V. , Sharma Vijay K. , Suthanthiran Manikkam , Muthukumar Thangamani 
Published: May 2022

AbstractThe frequently occurring T cell mediated rejection (TCMR) is a risk factor for allograft failure. Immunosuppressive therapy fails to reverse almost 40% of TCMRs occurring in human kidney allografts. A better understanding of the molecular mechanisms of TCMR and precision therapeutics may improve allograft longevity. We investigated adaptive immune landscape of TCMR by genome wide RNA sequencing of 34 prototypic kidney allograft biopsies from 34 adult recipients of human kidney allografts. Sixteen of the 34 biopsies were categorized as Banff TCMR and the remaining 18 as Banff Normal biopsies. Computational analysis identified higher intragraft abundance of the gene sets for key players of adaptive immune system in TCMR. TCMR allografts were characterized by, i) increased antigen processing and presentation and T cell receptor signaling, ii) increased memory T cells, Tregs, Th1, Th2 and Th17 subsets, iii) increased aerobic glycolysis of lymphocytes and reduced metabolic activity of graft parenchymal cells, iv) increased T cell inhibitory receptors and exhaustion markers, v) increased apoptosis and necroptosis, and vi) increased extracellular matrix remodeling, all in comparison to Normal biopsies. Our genome-wide transcriptomics provides an atlas of adaptive immune landscape of TCMR in human kidney allografts, help deduce molecular mechanisms and prioritization of therapeutic targets.
Adult Hox gene expression promotes periosteal stem cell maintenance and mediates reprogramming in a regionally restricted manner
Authors: Leclerc Kevin , Remark Lindsey H. , Ramsukh Malissa , Josephson Anne Marie , Morgani Sophie M. , Palma Laura , Parente Paulo EL , Lee Sooyeon , Lopez Emma Muiños , Leucht Philipp 
Published: May 2022

AbstractPeriosteal stem and progenitor cells are pivotal to the growth and lifelong turnover of bone and underpin its capacity to regenerate. Adjusting the potency of this cell population will therefore be critical to the successful generation and application of new bone repair therapies. Following their role in patterning the embryonic skeleton, Hox genes remain regionally expressed in mesenchymal stromal cell populations of the adult skeleton. Here we show that Hoxa10 is most expressed in the most uncommitted periosteal stem cell and that Hox maintains these skeletal stem cells in a multipotential, uncommitted state, thereby preventing their differentiation into bone. We demonstrate that Hoxa10 mediates the reprogramming of periosteal progenitors towards a stem cell state with greater self-renewal capacity and also establish that region-specific Hox genes mediate cell reprogramming in distinct anatomical regions, demonstrating the continued functional relevance of the embryonic Hox profile in adult stem cells. Together, our data describe a master regulator role of Hox in skeletal stem and progenitor cells and help provide insight into the development of cell-based therapies for treatment of at-risk bone fractures and other bone-related ailments.
The origin and evolution of mitochondrial tropism inMidichloriabacteria
Authors: Floriano Anna Maria , Batisti Biffignandi Gherard , Castelli Michele , Olivieri Emanuela , Clementi Emanuela , Comandatore Francesco , Rinaldi Laura , Opara Maxwell , Plantard Olivier , Palomar Ana M. , Noël Valérie , Vijay Amrita , Lo Nathan , Makepeace Benjamin L. , Duron Olivier , Jex Aaron , Guy Lionel , Sassera Davide 
Published: May 2022

AbstractMidichloriaare intracellular bacterial symbionts of ticks. Some representatives of this genus have the unique capability to colonize mitochondria in the cells of their hosts. Hypotheses on the nature of this interaction have proven difficult to test, partly due to a lack of data. Indeed, until now, mitochondrial tropism information and genomes were available only for symbionts of three and two tick host species, respectively. Here we analyzed the mitochondrial tropism of three additionalMidichloriaand sequenced nine novel genomes, showing that the tropism is pnon-monophyletic, either due to losses of the trait or multiple parallel acquisitions. Comparative genome analyses support the first hypothesis, as the genomes of non-mitochondrial symbionts appear to be reduced subsets of those capable of colonizing the organelles. We detect genomic signatures of mitochondrial tropism, showing a set of candidate genes characteristic of the strains capable of mitochondrial colonization. These include the type IV secretion system and the flagellum, which could allow the secretion of unique effectors, direct interaction with, or invasion of the mitochondria. Other genes, including putative adhesion molecules, proteins possibly involved in actin polymerization, cell wall and outer membrane proteins, are only present in mitochondrial symbionts. The bacteria could use these to manipulate host structures, including mitochondrial membranes, in order to fuse with the organelles or manipulate the mitochondrial network.
A Unified Catalog of 19,251 Non-human Reference Species Genomes Provides New Insights into the Mammalian Gut Microbiomes
Authors: Li Xiaoping , Tian Chen , Zhuang Daohua , Tian Liu , Shi Xingwei , Bai Yanli , Gao Han , Zhou Hong , Zhao Fangfang , Dai Min , Zhu Lei , Wu Qunfu , Liu Xiaotong , Zhang Tao , Sang Jianan , Sahu Sunil Kumar , Xu Xun , Jia Huijue , Liu Huan , Xiao Liang , Kristiansen Karsten , Zhang Zhigang 
Published: May 2022

AbstractThe gut microbiota is essential for host health and survival. Here, using samples from animals living in the Qinghai-Tibetan Plateau, we recovered 119,568 metagenome-assembled genomes (MAGs) that were clustered into 19,251 species-level genome bins (SGBs) of which most represent novel species. We present a novel mechanism shaping mammalian gut microbiomes using ancestral founder bacteria (AFB) as a core skeleton and recurring lineage-specific gains of microbial species that are transferred frequently among multiple hosts, not strictly limited by host phylogeny. Such lineage specific gains are responsible for increasing gut microbial diversity, maintaining functional stability, and endowing specific functions for host adaptions. Our analyses did not support the existence of co-phylogeny or co-speciation events between mammal hosts and their individual gut symbionts. The results presented in this study not only reveal novel unique gut microbial species and offer insight of value for understanding the diversity, stability, functionality of the mammalian gut microbiomes, and the co-evolution with their hosts, but also emphasize that animals living in extreme environments are a promising resource for the discovery of novel biological functions.
Insertions and deletions mediated functional divergence of Rossmann fold enzymes
Authors: Toledo-Patiño Saacnicteh , Pascarelli Stefano , Uechi Gen-ichiro , Laurino Paola 
Published: May 2022

AbstractNucleobase-containing coenzymes are considered the relics of an early RNA-based world that preceded the emergence of protein domains. Despite the importance of coenzyme-protein synergisms, their emergence and evolution remain poorly understood. An excellent target to address this issue is the Rossman fold, the most catalytically diverse and abundant protein architecture in Nature. Here, we investigatedted the two largest Rossman lineages, namely the nicotinamide adenine dinucleotide phosphate (NAD(P))-binding and the S-adenosyl methionine (SAM)-dependent superfamilies. With the aim to identify the evolutionary changes that lead to a switch in coenzyme specificity on these superfamilies, we performed structural and sequence-based Hidden Markov Models to systematically search for key motifs in their coenzyme-binding pockets. Our analyses revealed how insertions and deletions (InDels) reshaped the ancient β1−loop−α1 coenzyme-binding structure of NAD(P) into the well-defined SAM-binding β1−loop−α1 structure. To prove this observation experimentally, we removed an InDel of three amino acids from the NAD(P) coenzyme pocket and solved the structure of the resulting mutant, revealing the characteristic features of the SAM-binding pocket. To confirm the binding to SAM, we performed isothermal titration calorimetry measurements, validating the successful coenzyme switch. Molecular dynamics simulations also corroborated the role of InDels in abolishing NAD-binding and acquiring SAM binding. Our results uncovered how Nature utilized insertions and deletions to switch coenzyme specificity, and in turn, functionalities between these superfamilies. This work also establishes how protein structures could have been recycled through the course of evolution to adopt different coenzymes and confer different chemistries.Significance StatementCofactors are ubiquitous molecules necessary to drive about half of the enzymatic reactions in Nature. Among them, organic cofactors (coenzymes) that contain nucleotide moieties are believed to be relics of a hypothetical RNA world. Understanding coenzyme-binding transitions sheds light onto the emergence of the first enzymes and their chemical diversity. Rossmann enzymes bind to 7 out of 10 nucleotide coenzymes, representing an ideal target to study how different coenzyme specificities emerged and evolved. Here we demonstrated how insertions and deletions reshape coenzyme-specificity in Rossmann enzymes by retracing the emergence of the SAM-binding function from an NAD-binding ancestor. This work constitutes the first example of an evolutionary bridge between redox and methylation reactions, providing a new strategy to engineer coenzyme specificity.
The Limits of Molecular Signatures for Pancreatic Ductal Adenocarcinoma Subtyping
Authors: Lautizi Manuela , Baumbach Jan , Weichert Wilko , Steiger Katja , List Markus , Pfarr Nicole , Kacprowski Tim 
Published: May 2022

ABSTRACTMolecular signatures have been suggested as biomarkers to classify pancreatic ductal adenocarcinoma (PDAC) into two, three or four subtypes. Since the robustness of existing signatures is controversial, we performed a systematic evaluation of three established signatures for PDAC stratification across eight publicly available datasets. Clustering revealed inconsistency of subtypes across independent datasets and in some cases a different number of PDAC subgroups than in the original study, casting doubt on the actual number of existing subtypes. Next, we built nine classification models to investigate the ability of the signatures for tumor subtype prediction. The overall classification performance ranged from ∼35% to ∼90% accuracy, suggesting instability of the signatures. Notably, permuted subtypes and random gene sets achieved very similar performance. Cellular decomposition and functional pathway enrichment analysis revealed strong tissue-specificity of the predicted classes. Our study highlights severe limitations and inconsistencies that can be attributed to technical biases in sample preparation and tumor purity, suggesting that PDAC molecular signatures do not generalize across datasets. How stromal heterogeneity and immune compartment interplay in the diverging development of PDAC is still unclear. Therefore, a more mechanistic or at least multi-omic approach seems necessary to extract more robust and clinically exploitable insights.
Coexistence of Cue-specific and Cue-independent Spatial Representations for Landmarks and Self-motion Cues in Human Retrosplenial Cortex
Authors: Chen Xiaoli , Wei Ziwei , Wolbers Thomas 
Published: May 2022

AbstractLandmark-based and self-motion-based navigation are two fundamental forms of spatial navigation, which involve distinct cognitive mechanisms. A critical question is whether these two navigation modes invoke common or distinct spatial representations for a given environment in the brain. While a number of electrophysiological studies in non-human animals have investigated this question but yielded inconsistent results, it still awaits rigorous investigation in humans. In the current study, we combined ultra-high field fMRI at 7T and desktop virtual reality with state-of-the-art fMRI data analysis techniques. Using a novel linear track navigation task, we dissociated the use of landmarks and self-motion cues, so that participants used different spatial cues to encode and retrieve the same set of spatial locations. Focusing on the retrosplenial cortex (RSC) and the hippocampus, we observed that RSC contained both cue-specific and cue-independent spatial representations, which were driven by objective location (where the participant was actually located) and subjective location (the participant’s self-reported location), respectively. The hippocampus showed strong functional coupling with RSC and exhibited a similar spatial coding scheme, but with reduced effect sizes. Taken together, the current study demonstrated for the first time concurrent cue-specific and cue-independent spatial representations in RSC in the same spatial context, suggesting that this area might transform cue-specific spatial inputs into coherent cue-independent spatial representations to guide navigation behavior.
Multiplexed chromatin imaging reveals predominantly pairwise long-range coordination betweenDrosophilaPolycomb genes
Authors: Gurgo Julian , Walter Jean-Charles , Fiche Jean-Bernard , Houbron Christophe , Schaeffer Marie , Cavalli Giacomo , Bantignies Frédéric , Nollmann Marcelo 
Published: May 2022

AbstractPolycomb (Pc) group proteins are transcriptional regulators with key roles in development, cell identity and differentiation. Pc-bound chromatin regions form repressive domains that interact in 3D to assemble repressive nuclear compartments. Here, we used multiplexed chromatin imaging to investigate whether Pc compartments involve the clustering of multiple Pc domains during Drosophila development. Notably, 3D proximity between Pc targets is rare and involves predominantly pairwise interactions. These 3D proximities are particularly enhanced in segments where Pc genes are co-repressed. In addition, segment-specific expression ofHoxPc targets leads to their spatial segregation from Pc repressed genes. Finally, non-Hox Pc targets are proximal in regions where they are co-expressed. These results indicate that long-range Pc interactions are temporally and spatially regulated during differentiation and development but do not involve clustering of multiple distant Pc genes.
Dynamic allostery in substrate binding by human thymidylate synthase
Authors: Bonin Jeffrey P. , Sapienza Paul J. , Lee Andrew L. 
Published: May 2022

AbstractHuman thymidylate synthase (hTS) is essential for DNA replication and therefore a therapeutic target for cancer. Effective targeting requires knowledge of the mechanism(s) of regulation of this 72 kDa homodimeric enzyme. Here, we investigate the mechanism of binding cooperativity of the nucleotide substrate. We have employed exquisitely sensitive methyl-based CPMG and CEST NMR experiments enabling us to identify residues undergoing bifurcated linear 3-state exchange, including concerted switching between active and inactive conformations in the apo enzyme. The inactive state is populated to only ∼1.3%, indicating that conformational selection contributes negligibly to the cooperativity. Instead, methyl rotation axis order parameters, determined by 2H transverse relaxation rates, suggest that rigidification of the enzyme upon substrate binding is responsible for the entropically-driven cooperativity. Lack of the rigidification in product binding and substrate binding to an N-terminally truncated enzyme, both non-cooperative, support this idea. In addition, the lack of this rigidification in the N-terminal truncation indicates that interactions between the flexible N-terminus and the rest of the protein, which are perturbed by substrate binding, play a significant role in the cooperativity—a novel mechanism of dynamic allostery. Together, these findings yield a rare depth of insight into the substrate binding cooperativity of an essential enzyme.
Identification of differentially expressed novel tau associated proteins in transgenic AD model of Drosophila - a proteomic and in silico Approach
Authors: Chauhan Brijesh Singh , Garai Somenath , Singh Jyotsna , Srikrishna Saripella 
Published: May 2022

ABSTRACTAlzheimer’s disease (AD) is a memory related neurodegenerative disorder mainly associated with older adults. In this study, transgenic Drosophila AD model has been employed to investigate the tau associated proteome. Tau expression was specifically induced in the eye tissues and diseased fly heads were considered for proteomic studies with appropriate controls. We have identified 6 novel proteins from tau induced AD group by 2D and PD Quest analyses and further characterized them by in-vivo and in-silico approaches. The novel Tau interactors, [Obp44a Isoform A, Pglym Isoform A, IP15846p (Adh variant), RE45450p (mRpL2), Retinin, and Glob1 Isoform B], identified by MALDI-TOF/MS were validated through q-RT-PCR. The altered metabolic, behavioral and mitochondrial dynamics associated with Tau over expressing AD flies could be due to the altered expression of Odorant binding protein 44a (Obp44a) and mitochondrial ribosomal protein L2 (mRpL2), respectively. Further, we have showed for the first time the newly identified protein interaction with tau and other regulatory proteins through protein-protein docking, biocomputational classification and evolutionary relationship using in silico studies. Moreover, the study highlights the plausible role of these novel proteins in pathophysiology of phospho-tau induced AD flies and further help unraveling molecular pathways implicated in tauopathies.