bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinguishing COVID-19 infection and vaccination history by T cell reactivity
Authors: Yu Esther Dawen , Wang Eric , Garrigan Emily , Goodwin Benjamin , Sutherland Aaron , Chang James , Gálvez Rosa Isela , Mateus Jose , Rawlings Stephen A. , Smith Davey M. , Frazier April , Weiskopf Daniela , Dan Jennifer M. , Crotty Shane , Grifoni Alba , da Silva Antunes Ricardo , Sette Alessandro 
Published: December 2021

SUMMARYSARS-CoV-2 infection and COVID-19 vaccines elicit memory T cell responses. Here, we report the development of two new pools of Experimentally-defined T cell epitopes derived from the non-spike Remainder of the SARS-CoV-2 proteome (CD4RE and CD8RE). The combination of T cell responses to these new pools and Spike (S) were used to discriminate four groups of subjects with different SARS-CoV-2 infection and COVID-19 vaccine status: non-infected, non-vaccinated (I−V−); infected and non-vaccinated (I+V−); infected and then vaccinated (I+V+); and non-infected and vaccinated (I−V+). The overall classification accuracy based on 30 subjects/group was 89.2% in the original cohort and 88.5% in a validation cohort of 96 subjects. The T cell classification scheme was applicable to different mRNA vaccines, and different lengths of time post-infection/post-vaccination. T cell responses from breakthrough infections (infected vaccinees, V+I+) were also effectively segregated from the responses of vaccinated subjects using the same classification tool system. When all five groups where combined, for a total of 239 different subjects, the classification scheme performance was 86.6%. We anticipate that a T cell-based immunodiagnostic scheme able to classify subjects based on their vaccination and natural infection history will be an important tool for longitudinal monitoring of vaccination and aid in establishing SARS-CoV−2 correlates of protection.
Commercially-available heart rate monitor repurposed into a 9-gram standalone device for automatic arrhythmia detection with snapshot electrocardiographic capability: a pilot validation
Authors: Gaibazzi Nicola , Reverberi Claudio , Tuttolomondo Domenico , Di Maria Bernardo 
Published: December 2021

AbstractBackgroundThe usefulness of opportunistic arrhythmia screening strategies, using an electrocardiogram (ECG) or other methods for random “snapshot” assessments is limited by the unexpected and occasional nature of arrhythmias, leading to a high rate of missed-diagnosis.We have previously validated a cardiac monitoring system for AF detection pairing simple consumer-grade Bluetooth low-energy (BLE) heart rate (HR) sensors with a smartphone application (RITMIAtm, Heart Sentinel srl, Italy). In the current study we test a significant upgrade to the abovementioned system, thanks to the technical capability of new HR sensors to run algorithms on the sensor itself and to acquire (and store on-board) single-lead ECG strips, if asked to do so.Methods and ResultWe have reprogrammed a HR monitor intended for sports use (Movensense HR+) to run our proprietary RITMIA algorithm code in real-time, based on RR analysis, so that if any type of arrhythmia is detected it triggers a brief retrospective recording of a single-lead ECG, providing tracings of the specific arrhythmia for later consultation.We report the initial data on the behavior, feasibility and high diagnostic accuracy of this ultra-low weight customized device for standalone automatic arrhythmia detection and ECG recording, when several types of arrhythmias were simulated, under different baseline conditions.ConclusionsThe customized device was capable to detect all types of simulated arrhythmias and correctly triggered an visually interpretable ECG tracing. Future human studies are needed to address real-life accuracy of this device.
Pathogenic CD8 T cells defined by longitudinal liver sampling in chronic hepatitis B patients starting antiviral therapy
Authors: Nkongolo Shirin , Mahamed Deeqa , Kuipery Adrian , Sanchez Vasquez Juan D. , Kim Samuel C. , Mehrotra Aman , Patel Anjali , Hu Christine , McGilvray Ian , Feld Jordan J. , Fung Scott , Chen Diana , Wallin Jeffrey J. , Gaggar Anuj , Janssen Harry L. A. , Gehring Adam J. 
Published: December 2021

SummaryAccumulation of activated immune cells results in non-specific hepatocyte killing in chronic hepatitis B (CHB), leading to fibrosis and cirrhosis. We enrolled 15 CHB patients with active liver damage to receive antiviral therapy, and performed longitudinal liver sampling using fine-needle aspiration to investigate mechanisms of CHB pathogenesis in the human liver. Single-cell sequencing of total liver cells revealed a distinct liver-resident, polyclonal CD8 T cell population that was enriched at baseline and displayed a highly activated immune signature during liver damage. Cytokine combinations, identified by in silico prediction of ligand-receptor interaction, induced the activated phenotype in healthy liver CD8 T cells, resulting in non-specific Fas ligand-mediated killing of target cells. These results define a CD8 T cell population in the human liver that can drive pathogenesis, and a key pathway involved in their function in CHB patients.
Genome-wide association meta-analysis identifies novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation
Authors: Faro Valeria Lo , Bhattacharya Arjun , Zhou Wei , Zhou Dan , Wang Ying , Läll Kristi , Kanai Masahiro , Lopera-Maya Esteban , Straub Peter , Pawar Priyanka , Tao Ran , Zhong Xue , Namba Shinichi ,   the Global Biobank Meta-analysis Initiative, Sanna Serena , Nolte Ilja M. , Okada Yukinori , Ingold Nathan , MacGregor Stuart , Snieder Harold , Surakka Ida , Willer Cristen , Martin Alicia R. , Brantley Milam A. , Gamazon Eric R. , Jansonius Nomdo M. , Joos Karen , Cox Nancy J. , Hirbo Jibril 
Published: December 2021

AbstractPrimary open-angle glaucoma (POAG) is a leading cause of irreversible blindness globally. There is disparity in POAG prevalence and manifestations across ancestries. We identify novel and unique genetics that underlie POAG risk in different ancestries by performing meta-analysis across 15 biobanks (of the Global Biobank Meta-analysis Initiative) with previously multi-ancestry studies. 18 novel significant loci, three of which were ancestry-specific, and five sex-specific were identified. We performed gene-enrichment and transcriptome-wide association studies (TWAS), implicating vascular and cancer genes. A fifth of these genes are primary ciliary genes. Extensive statistical analysis of genes in theSIX6andCDKN2B-AS1loci (implicated in POAG, cardiovascular diseases and cancers) found interaction betweenSIX6and causal variants in chr9p21.3, with expression effect onCDKN2A/B. We infer that some POAG risk variants may be ancestry-specific, sex-specific, or both. Our results further support the contribution of vascular, cancer, and primary cilia genes in POAG pathogenesis.
A one health approach to investigating an outbreak of alimentary tick-borne encephalitis in a non-endemic area in France (Ain, Eastern France): a longitudinal serological study in livestock, detection in ticks, and the first TBE virus isolation and molecular characterization
Authors: Gonzalez Gaëlle , Bournez Laure , Moraes Rayane Amaral , Dumarest Marine , Galon Clémence , Vorimore Fabien , Cochin Maxime , Nougairède Antoine , Hennechart-Collette Catherine , Perelle Sylvie , Leparc-Goffart Isabelle , Durand Guillaume André , Grard Gilda , Bénet Thomas , Danjou Nathalie , Blanchin Martine , Lacour Sandrine A , Boué Franck , Chenut Guillaume , Mainguet Catherine , Simon Catherine , Brémont Laurence , Zientara Stephan , Moutailler Sara , Martin-Latil Sandra , Dheilly Nolwenn M , Beck Cécile , Lecollinet Sylvie 
Published: December 2021

AbstractTick borne encephalitis virus geographic range and human incidence is increasing throughout Europe, putting a number of non-endemic regions and countries at risk of outbreaks. In spring 2020, there was an outbreak of TBE in Ain, Eastern France, where the virus had never been detected before. All patients but one had consumed traditional unpasteurized raw goat cheese from a local producer. We conducted an investigation in the suspected farm using an integrative One Health approach. Our methodology included (i) the detection of virus in cheese and milk products, (ii) serological testing of all animals in the suspected farm and surrounding farms, (iii) an analysis of the landscape and localisation of wooded area, (iv) the capture of questing ticks and small mammals for virus detection and estimating enzootic hazard, and (v) virus isolation and genome sequencing. This approach allowed us to confirm the alimentary origin of the TBE outbreak and to witness in real time the seroconversion of recently exposed individuals and the excretion of virus in goat milk. In addition, we identified a wooded focus area where and around which there is a risk of TBEV exposure. We provide the first TBEV isolate responsible for as a source of dietary contamination in France, obtained its full-length genome sequence, and found that it does not cluster very closely neither with the isolate circulating in Alsace nor with any other isolate within the European lineage. TBEV is now a notifiable human disease in France, which should facilitate surveillance of TBEV incidence and distribution throughout France.
Partial recovery of amblyopia following fellow eye ischemic optic neuropathy
Authors: Resnick Hannah H. , Bear Mark F. , Gaier Eric D. 
Published: December 2021

AbstractBackgroundRecovery from amblyopia in adulthood following fellow eye (FE) vision loss is a well-known phenomenon. Incidence of recovery varies widely following different FE pathologies and rate of recovery following FE ischemic optic neuropathy (ION) has not been examined. We aimed to determine frequency and degree of improvement in amblyopic eye (AE) visual function following ION in the FE.MethodsWe performed a retrospective chart review of patients between 2007-2021 confirmed to have amblyopia and ischemic optic neuropathy in different eyes. Patients with unstable ocular pathology potentially limiting vision were excluded. We compared best-corrected visual acuity (VA) in each eye before and after FE ION over time. For patients with available data, we examined change in perimetric performance over time.ResultsAmong the 12 patients who met inclusion criteria (mean age 67±8 years), 9 (75%) improved ≥1 line and 2 (17%) improved ≥3 lines. Median time from ION symptom onset to maximal improvement was 6 months (range: 2-101 months). Reliable perimetric data were available for 6 patients. Mean sensitivity improved in the amblyopic eye for all patients, with a mean improvement of 1.9±1.1 dB. There was no correspondence between foci of ION-related field loss and gains in field sensitivity in the AE.ConclusionA high proportion of patients with amblyopia and contralateral ION experience improvement in their amblyopic eye. Modest gains in perimetric sensitivity in the AE may accompany FE ION. These findings support the view that residual plasticity in the adult visual cortex can be tapped to support functional improvement in amblyopia.
The quorum sensing com system regulates pneumococcal colonisation and invasive disease in a pseudo-stratified airway tissue model
Authors: Kahlert Christian R. , Nigg Susanne , Onder Lucas , Dijkman Ronald , Diener Liliane , Rodriguez Regulo , Vernazza Pietro , Thiel Volker , Vidal Jorge E. , Albrich Werner C. 
Published: December 2021

AbstractStreptococcus pneumoniae (Spn) colonises respiratory epithelia but can also invade lung cells causing pneumonia. We developed an ex vivo model with human airway epithelial (HAE) cells harvested from lung biopsies to study Spn colonisation and translocation. Flow-cytometry, confocal imaging and electron microscopy studies identified the epithelial lineage with signs of differentiation (beating cilia, mucus, and tight junctions). HAE cells were challenged with Spn wild-type TIGR4 (wtSpn) or its isogenic ΔcomC quorum sensing-deficient mutant. ΔcomC mutant colonised significantly less than wtSpn at 6 h post-inoculation but at significantly higher levels at 19 h and 30 h. Translocation correlated inversely with colonisation density. Transepithelial electric resistance (TEER) decreased after pneumococcal infection and correlated with increased translocation for both strains.Confocal imaging illustrated colocalisation of intracellular Spn with both cilia and zonulin-1 and prominent microcolony formation with wtSpn but disintegration of microcolony structures over time with ΔcomC mutant. ΔcomC caused a more pronounced release of both zonulin-1 and lactate dehydrogenase into the supernatant at later time points than wtSpn, suggesting that cytotoxicity is likely not the mechanism leading to translocation. There was a density- and time-dependent increase of inflammatory cytokines from human HAE cells infected with ΔcomC compared with wtSpn, including increased levels of the NLRP3 inflammasome-related IL-18.In conclusion, our experiments indicate that ComC system allows a higher organisational level of population structure resulting in microcolony formation, increased early colonisation and subsequent translocation. We propose that ComC inactivation unleashes a very different and possibly more virulent phenotype that merits further investigation.
RFX6-mediated dysregulation defines human β cell dysfunction in early type 2 diabetes
Authors: Walker John T. , Saunders Diane C. , Rai Vivek , Dai Chunhua , Orchard Peter , Hopkirk Alexander L. , Reihsmann Conrad V. , Tao Yicheng , Fan Simin , Shrestha Shristi , Varshney Arushi , Wright Jordan J. , Pettway Yasminye D. , Ventresca Christa , Agarwala Samir , Aramandla Radhika , Poffenberger Greg , Jenkins Regina , Hart Nathaniel J. , Greiner Dale L. , Shultz Leonard D. , Bottino Rita ,   Human Pancreas Analysis Program, Liu Jie , Parker Stephen C.J. , Powers Alvin C. , Brissova Marcela 
Published: December 2021

SUMMARYA hallmark of type 2 diabetes (T2D), a major cause of world-wide morbidity and mortality, is dysfunction of insulin-producing pancreatic islet β cells1–3. T2D genome-wide association studies (GWAS) have identified hundreds of signals, mostly in the non-coding genome and overlapping β cell regulatory elements, but translating these into biological mechanisms has been challenging4–6. To identify early disease-driving events, we performed single cell spatial proteomics, sorted cell transcriptomics, and assessed islet physiology on pancreatic tissue from short-duration T2D and control donors. Here, through integrative analyses of these diverse modalities, we show that multiple gene regulatory modules are associated with early-stage T2D β cell-intrinsic defects. One notable example is the transcription factor RFX6, which we show is a highly connected β cell hub gene that is reduced in T2D and governs a gene regulatory network associated with insulin secretion defects and T2D GWAS variants. We validated the critical role of RFX6 in β cells through direct perturbation in primary human islets followed by physiological and single nucleus multiome profiling, which showed reduced dynamic insulin secretion and large-scale changes in the β cell transcriptome and chromatin accessibility landscape. Understanding the molecular mechanisms of complex, systemic diseases necessitates integration of signals from multiple molecules, cells, organs, and individuals and thus we anticipate this approach will be a useful template to identify and validate key regulatory networks and master hub genes for other diseases or traits with GWAS data.
A new analytical pipeline reveals metatranscriptomic changes upon high-fat diet in a Down syndrome mouse model
Authors: Grabowicz Ilona E. , Herman-Iżycka Julia , Fructuoso Marta , Dierssen Mara , Wilczyński Bartek 
Published: December 2021

AbstractThe existing methods designated for metatranscriptomic studies are still rare and being developed. In this paper we present a new analytical pipeline combining contig assembly, gene selection and functional annotation. This pipeline allowed us to reconstruct contigs with very high unique mappability (83%) and select sequences encoding putative bacterial genes reaching also a very high (66%), unique mappability of the NGS sequencing reads. Then, we have applied our pipeline to study faecal metatranscriptome of a Down syndrome (DS) mouse model, the Ts65Dn mice, in order to identify the differentially expressed transcripts. Recent studies have implicated dysbiosis of gut microbiota in several central nervous system (CNS) disorders, including DS. Given that DS individuals have an increased prevalence of obesity, we also studied the effects of a high-fat diet (HFD) on the transcriptomic changes of mice gut microbiomes, as the complex symbiotic relationship between the gut microbiome and its host is strongly influenced by diet and nutrition. Using our new pipeline we found that compared to wild type (WT), Ts65Dn mice showed an elevated expression levels of genes involved in hypoxanthine metabolism, which contributes to oxidative stress, and a down-regulated expression of genes involved in interactions with host epithelial cells and virulence. Microbiomes of mice fed HFD showed significantly higher expression levels of genes involved in membrane lipopolysaccharides / lipids biosynthesis, and decreased expression of osmoprotection and lysine fermentation genes, among others. We also found evidence that mice microbiota is capable of expressing genes encoding for neuromodulators, which may play a role in development of compulsive overeating and obesity. Our results show a DS-specific metatranscriptome profile and show that a high-fat diet affects the metabolism of mice gut microbiome by changing activity of genes involved in lipids, sugars, proteins and amino acids metabolism and cell membranes turnover. Our new analytical pipeline combining contig assembly, gene selection and functional annotation provides new insights into the metatranscriptomic studies.
Investigation on the changes of Bifidobacterium and lactic acid bacteria in soybean meal fermented feed
Authors: Kang Lingyu , Chen Huayou , Feng Tao , Li Keyi , Ni Zhong , Gao Ebin , Yong Yangchun 
Published: December 2021

AbstractThe main objective of this research was to explore the dynamic changes of Bifidobacterium and lactic acid bacteria (LAB) in the process of feed fermentation under anaerobic condition, so as to increase the number of fermented bacteria of Bifidobacterium from the aspect of strain combination. The results showed that when Bifidobacterium lactis (B. lactis, i.e. Bifidobacterium animalis subsp. lactis) fermented with Bacillus coagulans or Lactobacillus paracasei, the maximum number of B. lactis in those samples was 9.42 times and 4.64 times of that of fermented sample with B. lactis only. The soybean meal was fermented by B. lactis, L. paracasei and B. coagulans, and the number of B. lactis reached the maximum after fermented 10 days, which was 6.13 times of that in unfermented sample. The reducing sugar content and highest activity of α-galactosidase were higher than the control. These results suggest that B. coagulans and L. paracasei can promote the growth of B. lactis. It is inferred that B. coagulans can metabolize normally in aerobic, micro-aerobic and anaerobic environments, consume oxygen, produce digestive enzymes, and cooperate with L. paracasei to produce metabolic products benefit for the growth of B. lactis.
High-affinity nanobodies as tools for structural and functional studies on mammalian Arc
Authors: Markússon Sigurbjörn , Hallin Erik I. , Bustad Helene J. , Raasakka Arne , Xu Ju , Muruganandam Gopinath , Loris Remy , Martinez Aurora , Bramham Clive R. , Kursula Petri 
Published: December 2021

AbstractActivity-regulated cytoskeleton-associated protein (Arc) is a multidomain protein of retroviral origin with a vital role in the regulation of synaptic plasticity and memory formation in mammals. However, the mechanistic and structural basis of Arc function is little understood. Arc has an NTD involved in membrane binding and a CTD which binds postsynaptic protein ligands. In addition, the NTD and CTD both function in Arc oligomerization, including assembly of retrovirus-like capsid involved in intercellular signaling. We produced and characterised six ultra-high-affinity anti-Arc nanobodies (Nb). The CTD of both rat and human Arc could be crystallised in ternary complexes with two Nbs simultaneously bound (H11 and C11). H11 binding deep into the stargazing-binding pocket of Arc CTD suggested competitive binding with Arc ligand peptides, which was confirmed in vitro. This indicates that the H11 Nb could serve as a genetically-encoded tool for inhibition of endogenous Arc N-lobe interactions in study of neuronal function and plasticity. The crystallisation of the human Arc CTD in two different conformations, accompanied by SAXS data and molecular dynamics simulations, paints a dynamic picture of the mammalian Arc CTD. Dynamics were affected by mutations known to inhibit capsid formation, implying a role for Arc CTD dynamics in oligomerisation. Dimerisation of the NTD, together with structural dynamics of the CTD, suggest a mechanism, by which structural dynamics of the CTD may promote capsomer formation, and dimerisation of the NTD links capsomers, facilitating the formation of capsids. The described recombinant ultrahigh-affinity anti-Arc Nbs are versatile tools that can be further developed for studying mammalian Arc structure and function in vitro and in vivo.
A brain atlas of synapse protein lifetime across the mouse lifespan
Authors: Bulovaite Edita , Qiu Zhen , Kratschke Maximilian , Zgraj Adrianna , Fricker David G. , Tuck Eleanor J. , Gokhale Ragini , Jami Shekib A. , Merino-Serrais Paula , Husi Elodie , O’Dell Thomas J. , DeFelipe Javier , Komiyama Noboru H. , Holtmaat Anthony , Fransén Erik , Grant Seth G.N. 
Published: December 2021

AbstractProtein turnover is required for synapse maintenance and remodelling and may impact memory duration. We quantified the lifetime of postsynaptic protein PSD95 in individual excitatory synapses across the mouse brain and lifespan, generating the Protein Lifetime Synaptome Atlas. Excitatory synapses have a wide range of protein lifetimes that may extend from a few hours to several months, with distinct spatial distributions in dendrites, neuron types and brain regions. Short protein lifetime (SPL) synapses are enriched in developing animals and in regions controlling innate behaviors, whereas long protein lifetime (LPL) synapses accumulate during development, are enriched in the cortex and CA1 where memories are stored, and are preferentially preserved in old age. The protein lifetime synaptome architecture is disrupted in an autism model, with synapse protein lifetime increased throughout the brain. These findings add a further layer to synapse diversity in the brain and enrich prevailing concepts in behavior, development, ageing and brain repair.
Controlling homology-directed repair outcomes in human stem cells with dCas9
Authors: Skarnes William C. , Ning Gang , Giansiracusa Sofia , Cruz Alexander S. , Blauwendraat Cornelis , Saavedra Brandon , Holden Kevin , Cookson Mark R. , Ward Michael E. , McDonough Justin A. 
Published: December 2021

AbstractModeling human disease in human stem cells requires precise, scarless editing of single nucleotide variants (SNV) on one or both chromosomes. Here we describe improved conditions for Cas9 RNP editing of SNVs that yield high rates of biallelic homology-directed repair. To recover both heterozygous and homozygous SNV clones, catalytically inactive ‘dCas9’was added to moderate high activity Cas9 RNPs. dCas9 can also block re-cutting and damage to SNV alleles engineered with non-overlapping guide RNAs.