bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein Representation Learning via Knowledge Enhanced Primary Structure Modeling
Authors: Zhou Hong-Yu , Fu Yunxiang , Zhang Zhicheng , Bian Cheng , Yu Yizhou 
Published: January 2023

AbstractProtein representation learning has primarily benefited from the remarkable development of language models (LMs). Accordingly, pre-trained protein models also suffer from a problem in LMs: a lack of factual knowledge. The recent solution models the relationships between protein and associated knowledge terms as the knowledge encoding objective. However, it fails to explore the relationships at a more granular level, i.e., the token level. To mitigate this, we propose Knowledge-exploited Auto-encoder for Protein (KeAP), which performs tokenlevel knowledge graph exploration for protein representation learning. In practice, non-masked amino acids iteratively query the associated knowledge tokens to extract and integrate helpful information for restoring masked amino acids via attention. We show that KeAP can consistently outperform the previous counterpart on 9 representative downstream applications, sometimes surpassing it by large margins. These results suggest that KeAP provides an alternative yet effective way to perform knowledge enhanced protein representation learning. Code and models are available athttps://github.com/RL4M/KeAP.
In vitroLung Epithelial Cell Model Reveals Novel Roles forPseudomonas aeruginosaSiderophores
Authors: Kang Donghoon , Xu Qi , Kirienko Natalia V. 
Published: January 2023

AbstractMultidrug-resistantPseudomonas aeruginosais a common nosocomial respiratory pathogen that continues to threaten the lives of patients with mechanical ventilation in intensive care units and those with underlying comorbidities such as cystic fibrosis or chronic obstructive pulmonary disease. For over 20 years, studies have repeatedly demonstrated that the major siderophore pyoverdine is an important virulence factor forP. aeruginosain invertebrate and mammalian hostsin vivo. Despite its physiological significance, anin vitro,mammalian cell culture model to characterize the impact and molecular mechanism of pyoverdine-mediated virulence has only been developed very recently. In this study, we adapt a previously-established, murine macrophage-based model for human bronchial epithelial cells (16HBE). We demonstrate that conditioned medium fromP. aeruginosainduced rapid 16HBE cell death through the pyoverdine-dependent secretion of cytotoxic rhamnolipids. Genetic or chemical disruption of pyoverdine biosynthesis decreased rhamnolipid production and mitigated cell death. Consistent with these observations, chemical depletion of lipid factors or genetic disruption of rhamnolipid biosynthesis was sufficient to abrogate conditioned medium toxicity. Furthermore, we also examine the effects of purified pyoverdine exposure on 16HBE cells. While pyoverdine accumulated within cells, the siderophore was largely sequestered within early endosomes, showing minimal cytotoxicity. More membrane-permeable iron chelators, such as the siderophore pyochelin, decreased epithelial cell viability and upregulated several proinflammatory genes. However, pyoverdine potentiated these iron chelators in activating proinflammatory pathways. Altogether, these findings suggest that the siderophores pyoverdine and pyochelin play distinct roles in virulence during acuteP. aeruginosalung infection.
Extracting nanoscale membrane morphology from single-molecule localizations
Authors: Marin Zach , Fuentes Lukas A. , Bewersdorf Joerg , Baddeley David 
Published: January 2023

ABSTRACTMembrane surface reconstruction at the nanometer scale is required for understanding mechanisms of subcellular shape change. This historically has been the domain of electron microscopy, but extraction of surfaces from specific labels is a difficult task in this imaging modality. Existing methods for extracting surfaces from fluorescence microscopy have poor resolution or require high-quality super-resolution data that is manually cleaned and curated. Here we present NanoWrap, a new method for extracting surfaces from generalized single-molecule localization microscopy (SMLM) data. This makes it possible to study the shape of specifically-labelled membraneous structures inside of cells. We validate NanoWrap using simulations and demonstrate its reconstruction capabilities on SMLM data of the endoplasmic reticulum and mitochondria. NanoWrap is implemented in the open-source Python Microscopy Environment.SIGNIFICANCEWe introduce a novel tool for reconstruction of subcellular membrane surfaces from single-molecule localization microscopy data and use it to visualize and quantify local shape and membrane-membrane interactions. We benchmark its performance on simulated data and demonstrate its fidelity to experimental data.
The Australasian dingo archetype:De novochromosome-length genome assembly, DNA methylome, and cranial morphology
Authors: Ballard J. William O. , Field Matt A. , Edwards Richard J. , Wilson Laura A.B. , Koungoulos Loukas G. , Rosen Benjamin D. , Chernoff Barry , Dudchenko Olga , Omer Arina , Keilwagen Jens , Skvortsova Ksenia , Bogdanovic Ozren , Chan Eva , Zammit Robert , Hayes Vanessa , Aiden Erez Lieberman 
Published: January 2023

AbstractBackgroundOne difficulty in testing the hypothesis that the Australasian dingo is a functional intermediate between wild wolves and domesticated breed dogs is that there is no reference specimen. Here we link a high-qualityde novolong read chromosomal assembly with epigenetic footprints and morphology to describe the Alpine dingo female named Cooinda. It was critical to establish an Alpine dingo reference because this ecotype occurs throughout coastal eastern Australia where the first drawings and descriptions were completed.FindingsWe generated a high-quality chromosome-level reference genome assembly (Canfam_ADS) using a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. Compared to the previously published Desert dingo assembly, there are large structural rearrangements on Chromosomes 11, 16, 25 and 26. Phylogenetic analyses of chromosomal data from Cooinda the Alpine dingo and nine previously publishedde novocanine assemblies show dingoes are monophyletic and basal to domestic dogs. Network analyses show that the mtDNA genome clusters within the southeastern lineage, as expected for an Alpine dingo. Comparison of regulatory regions identified two differentially methylated regions within glucagon receptor GCGR and histone deacetylase HDAC4 genes that are unmethylated in the Alpine dingo genome but hypermethylated in the Desert dingo. Morphological data, comprising geometric morphometric assessment of cranial morphology place dingo Cooinda within population-level variation for Alpine dingoes. Magnetic resonance imaging of brain tissue show she had a larger cranial capacity than a similar-sized domestic dog.ConclusionsThese combined data support the hypothesis that the dingo Cooinda fits the spectrum of genetic and morphological characteristics typical of the Alpine ecotype. We propose that she be considered the archetype specimen for future research investigating the evolutionary history, morphology, physiology, and ecology of dingoes. The female has been taxidermically prepared and is now at the Australian Museum, Sydney.
Bacterial mechanosensing of surface stiffness promotes signaling and growth leading to biofilm formation byPseudomonas aeruginosa
Authors: Wang Liyun , Wong Yu-Chern , Correira Joshua M. , Wancura Megan , Geiger Chris J , Webster Shanice S , Butler Benjamin J. , O’Toole George A. , Langford Richard M. , Brown Katherine A. , Dortdivanlioglu Berkin , Webb Lauren , Cosgriff-Hernandez Elizabeth , Gordon Vernita D. 
Published: January 2023

AbstractThe attachment of bacteria onto a surface, consequent signaling, and the accumulation and growth of the surface-bound bacterial population are key initial steps in the formation of pathogenic biofilms. While recent reports have hinted that the stiffness of a surface may affect the accumulation of bacteria on that surface, the processes that underlie bacterial perception of and response to surface stiffness are unknown. Furthermore, whether, and how, the surface stiffness impacts biofilm development, after initial accumulation, is not known. We use thin and thick hydrogels to create stiff and soft composite materials, respectively, with the same surface chemistry. Using quantitative microscopy, we find that the accumulation, motility, and growth of the opportunistic human pathogenPseudomonas aeruginosarespond to surface stiffness, and that these are linked through cyclic-di-GMP signaling that depends on surface stiffness. The mechanical cue stemming from surface stiffness is elucidated using finite-element modeling combined with experiments - adhesion to stiffer surfaces results in greater changes in mechanical stress and strain in the bacterial envelope than does adhesion to softer surfaces with identical surface chemistry. The cell-surface-exposed protein PilY1 acts as a mechanosensor, that upon surface engagement, results in higher cyclic-di-GMP levels, lower motility, and greater accumulation on stiffer surfaces. PilY1 impacts the biofilm lag phase, which is extended for bacteria attaching to stiffer surfaces. This study shows clear evidence that bacteria actively respond to different stiffness of surfaces where they adhereviaperceiving varied mechanical stress and strain upon surface engagement.ImportanceBacteria colonize many types of biological and medical surfaces with a large range of stiffnesses. Colonization leads to the formation of biofilms, which cause costly and life-impairing chronic infections. However, whether and how bacteria can sense and respond to the mechanical cue provided by surface stiffness has remained unknown. We find that bacteria do indeed respond to surface stiffness in a way that is both consistent with expectations based on equilibrium continuum mechanics and that quantitatively impacts multiple aspects of early biofilm formation. This is a new understanding for the nascent field of bacterial mechanobiology. Furthermore, this finding suggests the possibility of a new category of approaches to hindering biofilm development by tuning the mechanical properties of biomedical surfaces.
Streptococcus pneumoniaedrives specific and lasting Natural Killer cell memory
Authors: Camarasa Tiphaine M.N. , Torné Júlia , Chevalier Christine , Rasid Orhan , Hamon Melanie Anne 
Published: January 2023

AbstractNK cells are important mediators of innate immunity and play an essential role for host protection against infection, although their responses to bacteria are poorly understood. Recently NK cells were shown to display memory properties, as characterized by an epigenetic signature leading to a stronger secondary response. Although NK cell memory could be a promising mechanism to fight against infection, it has not been described upon bacterial infection. Here, we reveal that NK cells develop specific and long-term memory following sub-lethal infection with the extracellular pathogenStreptococcus pneumoniae. Memory NK cells display intrinsic sensing and response to bacteriain vitro, in a manner that is enhanced post-bacterial infection. In addition, their transfer into naïve mice confer protection from lethal infection for at least 12 weeks. Interestingly, NK cells display enhanced cytotoxic molecule production upon secondary stimulation and their protective role is dependent on Perforin and independent of IFNγ. Thus, our study identifies a new role for NK cells during bacterial infection, opening the possibility to harness innate immune memory for therapeutic purposes.
Differences in Neuropsychiatric Features in Black and White Individuals Diagnosed with Frontotemporal Degeneration
Authors: Jin Hannah , McMillan Corey T. , Yannatos Isabel , Fisher Lauren , Rhodes Emma , Jacoby Sarah F. , Irwin David J. , Massimo Lauren 
Published: January 2023

ABSTRACTBackgroundNeuropsychiatric symptoms are highly prevalent in frontotemporal degeneration (FTD). Prior research suggests there are disparities in the clinical presentation of dementia when comparing Black and White individuals but this has not been investigated in the context of FTD specifically. The aim of the present study is to investigate racial disparities in dementia severity, functional impairment and neuropsychiatric symptoms in individuals with a clinical diagnosis of FTD.MethodsUsing National Alzheimer’s Coordinating Center (NACC) data, we evaluated 63 Black and 2,356 White individuals living with a clinical diagnosis of FTD (behavioral variant FTD or primary progressive aphasia) and a healthy control group of 1899 Black and 9122 White individuals with normal behavior and cognition. We compared demographic characteristics, dementia severity, functional impairment and neuropsychiatric symptoms at initial NACC visit by examining differences on Clinical Dementia Rating Scale (CDR), Functional Assessment Scale (FAS) and Neuropsychiatric Inventory (NPI) using multivariable linear and logistic regression models, covarying for age at visit, disease duration, sex, and education. Models evaluating differences in neuropsychiatric symptoms additionally controlled for dementia severity.ResultsBlack individuals with FTD were considerably underrepresented, comprising only 2.5% of the clincial sample. In comparison to White individuals, Black individuals with FTD had a higher degree of dementia severity on CDR (CDR sum of boxes; p=0.03 CDR global, p=.006), greater functional impairment (FAS total; p=0.01) and more delusions (p=0.01), agitation (p=0.04) and depression (p=0.03) on the NPI. White individuals with FTD were more likely to demonstrate apathy (p=0.03). Within the normal control group, Black individuals reported less depression, anxiety, agitation, and nighttime behaviors (depression; p < 0.001; anxiety; p = 0.006; agitation; p = 0.048; nighttime behaviors; p < 0.001) compared to White normal controls.DiscussionThe present study suggests there are significant disparities in dementia severity, functional impairment and neuropsychiatric presentations at initial visit between Black and White individuals with FTD. Future work must address racial disparities in FTD and their underlying social determinants as well as the lack of representation of non-White individuals in nationally representative neurodegenerative disease registries in order identify appropriate interventions.
Barriers and opportunities relating to the implementation and evaluation of a complex digital intervention in England: A case study of Greater Manchester Diabetes My Way
Authors: Goldthorpe Joanna , Allen Tommy , Rutter Martin K , Brooks Joanna 
Published: January 2023

AbstractIntroductionDigital diabetes management systems have the potential to deliver cost-effective, flexible self-management support to patients with type 2 diabetes. DiabetesMyWay (DMW) is a platform for an open access website that aims to support diabetes self-management and provide patients with access to their care records. We present a case study focusing on a project involving patients across the large urban area of Greater Manchester (GM).MethodsInterviews were undertaken with 8 members of the project team and 3 patients using the platform. Data were analysed thematically using the template analysis approach.ResultsThree themes are presented: Complex approvals, permissions and access across multiple organisations and systems; Capacity challenges in primary care settings; Ongoing support for the project. Implementation and evaluation of GMDMW involved navigating data sharing systems and regulations for complex private and public sector organisations and these impacted on the electronic data sharing necessary for the DMW platform to work as intended. Participants felt that the complexities associated with merging different systems, operated by different organisations, with different data controllers and data owners were greater than anticipated.DiscussionThe complexity, number of organisations and levels of governance involved in implementing and evaluating GMDMW were barriers to implementation and evaluation. This reflects inherent problems around mobilising innovation in the NHS. Our findings can help the development and evaluation electronic interventions to improve health to navigate this complex research landscape and ensure that patients can access the most innovative and effective ways to support their health. (245/250 words)Author summaryDigital health interventions and Public Private Partnerships for innovation in the NHS are on the rise and in order to establish efficacy, these need to be evaluated. Often, this research and evaluation is carried out by Universities. However, challenges around navigating governance across these complex, multiple organisations exist where there is a need to share data and collaborate across systems effectively. Here, we describe the many unexpected challenges and solutions to effective data sharing reported by professionals and patients involved in the delivery and evaluation of a UK-based NHS/ private sector collaboration to provide a digital platform to support self-management of diabetes.
The effects of physiotherapy programs in COVID-19 patients during admission in the hospital
Authors: Jianramas Netchanok , Nissapatorn Veeranoot , Sivakorn Chaisith , de Lourdes Pereira Maria , Ratnarathon Anuttra (Chaovavanich) , Salesingh Chenpak , Jaiyen Eittipad , Chaiyakul Salinee , Piya-amornphan Nitita , Semphuet Thanaporn , Thiangtham Thanrada , Boontam Kornchanok , Longlalerng Khomkrip 
Published: January 2023

AbstractBackground and aimsSeveral recommendations exist regarding the role of physiotherapy programs (PTPs) in COVID-19 patients. However, none of the studies examines the frequency of bedside PTPs during admission. Thus, this study aimed to compare the different bedside PTPs frequencies on the survival rate, length of hospitalization (LoH), referrals to the intensive care unit (ICU), and in-hospital complications. The safety of patients and the physiotherapist was also investigated.MethodsFifty-two COVID-19 patients were equally assigned into two groups matched on gender and age (1:1 ratio). Experimental group one received 1-2 times of PTPs during hospitalization, and experimental group two received daily PTPs until hospital discharge. The primary outcomes were the survival rate, LoH, referrals to ICU, and in-hospital complications. The secondary outcomes were the adverse events for patients and the number of physiotherapists who contracted with COVID-19.ResultsMost participants were classified as having mild to moderate COVID-19 with a mean age of 45 years. There were no differences between groups in all primary outcome measures (all p > 0.05). The overall survival rate was 98%. One participant from the Ex-G2 group was referred to the ICU. Two Ex-G1 and four Ex-G2 participants had complications. There were no immediate serious adverse events found after PTPs for both groups. None of the physiotherapists tested positive for COVID-19.ConclusionIn COVID-19 patients with mild to moderate conditions, one to two bedside PTPs were enough to achieve the same results as patients who received daily PTPs. PTPs were safe for COVID-19 patients, and physiotherapists.CLINICAL REGISTRATION NUMBERThai Clinical Trials,https://www.thaiclinicaltrials.org/, TCTR20210823004.
Steamed broccoli sprouts alleviate DSS-induced inflammation and retain gut microbial biogeography in mice
Authors: Holman Johanna M. , Colucci Louisa , Baudewyns Dorien , Balkan Joe , Hunt Timothy , Hunt Benjamin , Kinney Marissa , Holcomb Lola , Chen Grace , Moses Peter L. , Mawe Gary M. , Zhang Tao , Li Yanyan , Ishaq Suzanne L. 
Published: January 2023

AbstractInflammatory Bowel Diseases (IBD) are devastating conditions of the gastrointestinal tract with limited treatments, and dietary intervention may be effective, and affordable, for managing symptoms. Glucosinolate compounds are highly concentrated in broccoli sprouts, especially glucoraphanin, and can be metabolized by certain mammalian gut bacteria into anti inflammatory isothiocyanates, such as sulforaphane. Gut microbiota exhibit biogeographic patterns, but it is unknown if colitis alters these or whether the location of glucoraphanin metabolizing bacteria affects anti-inflammatory benefits. We fed specific pathogen free C57BL/6 mice either a control diet or a 10% steamed broccoli sprout diet, and gave a three-cycle regimen of 2.5% dextran sodium sulfate (DSS) in drinking water over a 34-day experiment to simulate chronic, relapsing ulcerative colitis. We monitored body weight, fecal characteristics, lipocalin, serum cytokines, and bacterial communities from the luminal and mucosa-associated populations in the jejunum, cecum, and colon. Mice fed the broccoli sprout diet with DSS treatment performed better than mice fed the control diet with DSS, including significantly more weight gain, lower Disease Activity Indexes, lower plasma lipocalin and proinflammatory cytokines, and higher bacterial richness in all gut locations. Bacterial communities were assorted by gut location, but were more homogenous across locations in the control diet + DSS mice. Importantly, our results showed that broccoli sprout feeding abrogated the effects of DSS on gut microbiota, as bacterial richness and biogeography were similar between mice receiving broccoli sprouts with and without DSS. Collectively, these results support the protective effect of steamed broccoli sprouts against dysbiosis and colitis induced by DSS.ImportanceEvaluating bacterial communities across different locations in the gut provides a greater insight than fecal samples alone, and provides an additional metric by which to evaluate beneficial host-microbe interactions. Here, we show that 10% steamed broccoli sprouts in the diet protects mice from the negative effects of dextran sodium sulfate induced colitis, that colitis erases biogeographical patterns of bacterial communities in the gut, and that the cecum is not likely to be a significant contributor to colonic bacteria of interest in the DSS mouse model of ulcerative colitis. Mice fed the broccoli sprout diet during colitis performed better than mice fed the control diet while receiving DSS. The identification of accessible dietary components and concentrations that help maintain and correct the gut microbiome may provide universal and equitable approaches to IBD prevention and recovery, and broccoli sprouts represent a promising strategy.
Dynamic fate map of hindbrain rhombomeres in zebrafish
Authors: Kamaraj Mageshi , Savy Thierry , Desnoulez Sophie Salomé , Peyrieras Nadine , Frain Monique 
Published: January 2023

AbstractUnderstanding of the morphogenetic processes that underlie the patterning of the vertebrate hindbrain requires establishment of rhombomere (r) cell lineages. Using long termin vivotwo-photon imaging of zebrafish transgenic lines and automated image processing tools, we provide a method to reconstruct the r2-r6 lineage trees from the onset of gastrulation through early neurulation. We provide a dynamic fate map of hindbrain patterning at single-cell resolution. We show that rhombomere progenitor domains are aligned along the anteroposterior (AP) and dorsoventral (DV) axes as early as the shield stage. Rhombomere progenitor domains show a segmental organization, parallel to the blastoderm margin that predicts the future AP order of hindbrain. The DV organization of rhombomeres is set by the segregation of the progenitors along the DV axis of the embryo. Progenitors located at the dorsal/medial part of the blastoderm form the ventral domain of the rhombomeres while the lateral progenitors constitute the dorsal part. Our study sheds light on the clonal origin of individual rhombomeres, spatial and temporal patterns of cell division and migration of rhombomere progenitors throughout the early steps of hindbrain morphogenesis.