bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiratory Virus Circulation during the First Year of the COVID-19 Pandemic in the Household Influenza Vaccine Evaluation (HIVE) Cohort
Authors: Fine Sydney R. , Bazzi Latifa A. , Callear Amy P. , Petrie Joshua G. , Malosh Ryan E. , Tucker Joshua E. , Smith Matthew , Ibiebele Jessica , McDermott Adrian , Rolfes Melissa A. , Monto Arnold S. , Martin Emily T. 
Published: December 2022

ABSTRACTBackgroundThe annual reappearance of respiratory viruses has been recognized for decades. The onset of the COVID-19 pandemic altered typical respiratory virus transmission patterns. COVID-19 mitigation measures taken during the pandemic were targeted at SARS-CoV-2 respiratory transmission and thus broadly impacted the burden of acute respiratory illnesses (ARIs), in general.MethodsWe used the longitudinal Household Influenza Vaccine Evaluation (HIVE) cohort of households in southeast Michigan to characterize mitigation strategy adherence, respiratory illness burden, and the circulation of 15 respiratory viruses during the COVID-19 pandemic determined by RT-PCR of respiratory specimens collected at illness onset. Study participants were surveyed twice during the study period (March 1, 2020, to June 30, 2021), and serologic specimens were collected for antibody measurement by electrochemiluminescence immunoassay. Incidence rates of ARI reports and virus detections were calculated and compared using incidence rate ratios for the study period and a pre-pandemic period of similar length.ResultsOverall, 437 participants reported a total of 772 ARIs and 329 specimens (42.6%) had respiratory viruses detected. Rhinoviruses were the most frequently detected organism, but seasonal coronaviruses—excluding SARS-CoV-2—were also common. Illness reports and percent positivity were lowest from May to August 2020, when mitigation measures were most stringent. Study participants were more adherent to mitigation measures in the first survey compared with the second survey. Supplemental serology surveillance identified 5.3% seropositivity for SARS-CoV-2 in summer 2020; 3.0% between fall 2020 and winter 2021; and 11.3% in spring 2021. Compared to a pre-pandemic period of similar length, the incidence rate of total reported ARIs for the study period was 50% lower (95% CI: 0.5, 0.6; p<0.001) than the incidence rate from March 1, 2016, to June 30, 2017.ConclusionsThe burden of ARI in the HIVE cohort during the COVID-19 pandemic fluctuated, with declines occurring concurrently with the widespread use of public health measures. It is notable, however, that rhinovirus and seasonal coronaviruses continued to circulate even as influenza and SARS-CoV-2 circulation was low.
Duration of viral shedding of the Omicron variant in asymptomatic and mild COVID-19 cases from Shanghai, China
Authors: Sun Weijie , Yang Naibin , Mao Yang , Yan Danying , Song Qifa , Qian Guoqing 
Published: December 2022

AbstractBackgroundThe Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), designated as a variant of concern by the World Health Organization, spreads globally and was confirmed as the cause of the Omicron wave of the coronavirus disease 2019 (COVID-19) pandemic in Shanghai, China. The viral shedding duration of Omicron variants needs to be determined.MethodsWe retrospectively analyzed 382 patients admitted to a shelter hospital for COVID-19. Of the patients, 8 patients were referred to a designated hospital, 100 were infected asymptomatic patients, and 274 patients had mild COVID-19.ResultsThe vaccination rates (including fully and boosted) in the asymptomatic and mild COVID-19 patients were 92.00% and 94.16%, respectively. Majority of the studied population showed a first reverse transcription-polymerase chain reaction cycle threshold (Ct) value of 20. For 2565 nasopharyngeal swabs from close or sub-close contacts, the Ct value gradually increased to 35 for 8 days, and the median duration of viral shedding time was 10 days after the first positive detection of the SARS-CoV-2 nuclei acid.ConclusionsQuantitative viral RNA load assays in COVID-19 (BA.2.2.1) close or sub-closed contacts could be used to prevent transmissions and control precautions.
First gene-edited calf with reduced susceptibility to a major viral pathogen
Authors: Workman Aspen M , Heaton Michael P , Vander Ley Brian L , Webster Dennis A , Sherry Luke , Larson Sabreena , Kalbfleisch Theodore S , Harhay Gregory P , Jobman Erin E , Carlson Daniel F , Sonstegard Tad S 
Published: December 2022

AbstractBovine viral diarrhea virus (BVDV) is one of the most important viruses affecting the health and well-being of bovine species throughout the world. Here we used CRISPR-mediated homology-directed repair and somatic cell nuclear transfer to produce a live calf with a six amino acid substitution in the BVDV binding domain of bovine CD46. The result was a gene-edited calf with dramatically reduced susceptibility to infection as measured by clinical signs and the lack of viral infection in white blood cells. The edited calf has no off-target edits and appears normal and healthy at 16 months of age without obvious adverse effects from the on-target edit. This precision bred, proof-of-concept animal provides the first evidence that intentional genome alterations in CD46 may reduce the burden of BVDV-associated diseases in cattle, and is consistent with our stepwise,in vitroandex vivoexperiments with cell lines and matched fetal clones.
Dynamics and composition of small heat shock protein condensates and aggregates
Authors: Joosten Joep , van Sluijs Bob , Egberts Wilma Vree , Emmaneel Martin , Jansen Pascal W.T.C. , Vermeulen Michiel , Boelens Wilbert , Bonger Kimberly M. , Spruijt Evan 
Published: December 2022

SummarySmall heat shock proteins (sHSPs) are essential ATP-independent chaperones that protect the cellular proteome during stress. These proteins assemble into polydisperse oligomeric structures, the composition of which dramatically affects their chaperone activity. The biomolecular consequences of variations in sHSP ratios, especially inside living cells, remain elusive. Here, we study the consequences of altering the relative expression levels of HspB2 and HspB3. These chaperones are partners in a hetero-oligomeric complex, and genetic mutations that abolish their mutual interaction are associated with myopathic disorders.HspB2 displays three distinct phenotypes when co-expressed with HspB3 at varying ratios. Expression of HspB2 alone lead to formation of liquid nuclear condensates, while shifting the stoichiometry towards HspB3 resulted in the formation of large solid-like aggregates. Only cells co-expressing HspB2 with a limited amount of HspB3 showed a homogeneous nuclear distribution of HspB2. Strikingly, both condensates and aggregates were reversible, as shifting the HspB2:HspB3 balance in situ resulted in dissolution of these structures.To uncover the molecular composition of HspB2 condensates and aggregates, we used APEX-mediated proximity labelling. Most proteins interact transiently with the condensates and were neither enriched nor depleted. In contrast, we found that HspB2:HspB3 aggregates sequestered several disordered proteins among which autophagy factors, suggesting that the cell is actively attempting to clear these aggregates. This study presents a striking example of how changes in the relative expression levels of interacting proteins affects their phase behavior. Our approach can be a useful tool to study the role of protein stoichiometry in other biomolecular condensates.Graphical abstractHighlights-Small heat shock protein hetero-oligomerization affects their chaperone function-The HspB2:HspB3 expression ratio determines phase separation and aggregation-HspB2 condensates and HspB2:HspB3 aggregates are fully reversible-Proximity labelling unveils autophagy factor recruitment to HspB2:HspB3 aggregates-Stoichiometry-dependant regulation of phase behaviour may be widespread in biology
Multiple antagonist calcium-dependent mechanisms control CaM Kinase-1 subcellular localization in aC. elegansthermal nociceptor
Authors: Ippolito Domenica , Glauser Dominique 
Published: December 2022

ABSTRACTNociceptive habituation is a conserved process through which pain-sensitivity threshold is adjusted based on past sensory experience and which may be dysregulated in human chronic pain conditions. Noxious heat habituation inC. elegansinvolves the nuclear translocation of CaM kinase-1 (CMK-1) in the FLP thermo-nociceptors neurons, causing reduced animal heat sensitivity and avoidance responses. The phosphorylation of CMK-1 on T179 by CaM kinase kinase-1 (CKK-1) is required for nuclear entry. Recently, we identified a specific Nuclear Export Sequence (NES) required to maintain CMK-1 in the cytoplasm at rest (20 °C) and showed that Ca2+/CaM binding is sufficient to enhance CMK-1 affinity for IMA-3 via a specific Nuclear Localization Signal (NLS) in order to promote nuclear entry after persistent heat stimulation (90 min at 28°C) (Ippolitoet al., 2021). Here, we identified additional functional NES and NLS on CMK-1, whose activity can counteract previously identified elements. Furthermore, we clarify the relationship between the CaM-binding-dependent and T179-dependent effects. T179 phosphorylation can promotes nuclear entry both downstream of CaM-binding and as part of an independent/parallel pathway. Moreover, T179 phosphorylation can also produce the opposite effect by promoting nuclear export. Taken together, our studies show that multiple calcium-dependent regulatory mechanisms converge to bias the activity pattern across a network of NES/NLS elements, in order to activate CMK-1 nucleo-cytoplasmic shuttling, change its localization equilibrium and actuate stimulation-dependent nociceptive plasticity.
Skeletal muscle hypertrophy rewires glucose metabolism: an experimental investigation and systematic review
Authors: Baumert Philipp , Mäntyselkä Sakari , Schönfelder Martin , Heiber Marie , Jacobs Mika Jos , Swaminathan Anandini , Minderis Petras , Dirmontas Mantas , Kleigrewe Karin , Meng Chen , Gigl Michael , Ahmetov Ildus I. , Venckunas Tomas , Degens Hans , Ratkevicius Aivaras , Hulmi Juha J. , Wackerhage Henning 
Published: December 2022

ABSTRACTBackgroundProliferating cancer cells shift their metabolism toward glycolysis even in the presence of oxygen to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodeling occurs during skeletal muscle hypertrophy.MethodsWe used mass spectrometry in hypertrophying C2C12 myotubesin vitroand plantaris mice musclein vivoand assessed metabolomic changes and the incorporation of [U-13C6]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, UK Biobank was used to link the findings to population level.ResultsThe metabolomics analysis in myotubes revealed IGF-1 induced altered metabolite concentrations in anabolic pathways such as in the pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; p=0.01) and serine synthesis pathway (serine: - 36.8%; p=0.009). Like the hypertrophy-stimulation with IGF-1 in myotubesin vitro, the concentration of the dipeptide L-carnosine was decreased by 26.6% (p=0.001) during skeletal muscle growthin vivo.However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (p=0.004) in the overloaded musclein vivo, while increased in the IGF-1 stimulated myotubesin vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-13C6]glucose is increasingly incorporated by ∼13% (p=0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (p=0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (p<0.001) highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n=450,243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDHandPSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (p<5.0e-8).ConclusionUnderstanding the mechanisms that regulates skeletal muscle mass will help in developing effective treatments against muscle weakness. Our results provide evidence for metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in the serine synthesis.
Atlas-scale single-cell multi-sample multi-condition data integration using scMerge2
Authors: Lin Yingxin , Cao Yue , Willie Elijah , Patrick Ellis , Yang Jean Y.H. 
Published: December 2022

AbstractThe recent emergence of multi-sample multi-condition single-cell multi-cohort studies allow researchers to investigate different cell states. The effective integration of multiple large-cohort studies promises biological insights into cells under different conditions that individual studies cannot provide. Here, we present scMerge2, a scalable algorithm that allows data integration of atlas-scale multi-sample multi-condition single-cell studies. We have generalised scMerge2 to enable the merging of millions of cells from single-cell studies generated by various single-cell technologies. Using a large COVID-19 data collection with over five million cells from 1000+ individuals, we demonstrate that scMerge2 enables multi-sample multi-condition scRNA-seq data integration from multiple cohorts and reveals signatures derived from cell-type expression that are more accurate in discriminating disease progression. Further, we demonstrate that scMerge2 can remove dataset variability in CyTOF, imaging mass cytometry and CITE-seq experiments, demonstrating its applicability to a broad spectrum of single-cell profiling technologies.
STOmics-GenX: CRISPR based approach to improve cell identity specific gene detection from spatially resolved transcriptomics
Authors: Currenti Jennifer , Qiao Liang , Pai Rhea , Gupta Saurabh , Khyriem Costerwell , Wise Kellie , Sun Xiaohuan , Armstrong Jon , Crane Jordan , Pathak Smita , Yang Bicheng , George Jacob , Plummer Jasmine , Martelotto Luciano , Sharma Ankur 
Published: December 2022

ABSTRACTThe spatial organisation of cells defines the biological functions of tissue ecosystems from development to disease. Recently, an array of technologies have been developed to query gene expression in a spatial context. These include techniques such as employing barcoded oligonucleotides, single-molecule fluorescence in situ hybridization (smFISH), and DNA nanoball (DNB)-patterned arrays. However, resolution and efficiency vary across platforms and technologies. To obtain spatially relevant biological information from spatially resolved transcriptomics, we combined the Stereo-seq workflow with CRISPRclean technology to develop the STOmics-GenX pipeline. STOmics-GenX not only allowed us to reduce genomic, mitochondrial, and ribosomal reads, but also lead to a ∼2.1-fold increase in the number of detected genes when compared to conventional Stereo-seq (STOmics). Additionally, the STOmics-GenX pipeline resulted in an improved detection of cell type specific genes, thereby improving cellular annotations. Most importantly, STOmics-GenX allowed for enhanced detection of clinically relevant biomarkers such as Alpha-fetoprotein (AFP), enabling the identification of two spatially distinct subsets of hepatocytes in hepatocellular carcinoma tissue. Thereby, combining CRISPRclean technology with STOmics not only allowed improved gene detection but also paved the way for spatial precision oncology by improved detection of clinically relevant biomarkers.
Visuomotor interactions in the mouse forebrain mediated by extrastriate cortico-cortical pathways
Authors: Hovde Karoline , Rautio Ida V. , Hegstad Andrea M. , Witter Menno P. , Whitlock Jonathan R. 
Published: December 2022

AbstractThe mammalian visual system can be broadly divided into two functional processing pathways: a dorsal stream supporting visually and spatially guided actions, and a ventral stream enabling object recognition. In rodents, the majority of visual signaling in the dorsal stream is transmitted to frontal motor cortices via extrastriate visual areas surrounding V1, but exactly where and to what extent V1 feeds into motor-projecting visual regions is not well known. To address this we employed a dual labeling strategy in male and female mice in which efferent projections from V1 were labeled anterogradely, and motor-projecting neurons in higher visual areas were labeled with retrogradely traveling adeno-associated virus (rAAV-retro) injected in M2. In flattened sections of dorsal cortex, the most pronounced colocalization V1 output and M2 input occurred in extrastriate areas AM, PM, RL and AL. Coronal sections further showed that neurons in both superficial and deep layers in these regions project to M2, but high resolution volumetric reconstructions revealed that the vast majority of putative synaptic contacts from V1 onto M2-projecting neurons occurred in layer 2/3. These findings support the existence of a dorsal processing stream in the mouse visual system, where visual signals reach motor cortex largely via feedforward projections in anteriorly and medially located extrastriate areas.Significance StatementVisually guided motor behavior depends on the long-distance relay of signals from visual cortex to frontal motor cortices, but the neuroanatomical connections linking visual and motor systems in rodents are not fully charted. Here, we characterized such pathways by injecting anterograde tracers in primary visual cortex (V1) and retrogradely traveling virus in motor cortex (M2), and visualizing where the projections overlapped. We found preferential colocalization of V1 output and M2-projecting neurons in anteriorly- and medially-located higher visual areas. 3D volumetric reconstructions further showed high rates of putative synaptic connections mainly in superficial layers. Thus, visual signals in the mouse dorsal visual stream reach motor areas at least in part via superficial, feedforward connections in a subset of extrastriate areas.
Repeated evolution of bedaquiline resistance inMycobacterium tuberculosisis driven by truncation ofmmpR5
Authors: Roberts Leah W , Malone Kerri M , Hunt Martin , Joseph Lavania , Wintringer Penelope , Knaggs Jeff , Crook Derrick , Farhat Maha R , Iqbal Zamin , Omar Shaheed V 
Published: December 2022

AbstractThe antibiotic Bedaquiline (BDQ) is a key component of new WHO regimens for drug resistant tuberculosis (TB) but predicting BDQ resistance (BDQ-R) from genotypes remains challenging. We analysed a collection (n=505) ofMycobacterium tuberculosisfrom two high prevalence areas in South Africa (Cape Town and Johannesburg, 2019-2020), and found 53 independent acquisitions of 31 different mutations within themmpR5regulatory gene, with a particular enrichment of truncated MmpR5 in BDQ-R isolates by either frameshift or introduction of an insertion element. Truncations occurred across threeM. tuberculosislineages, impacting 66% of BDQ-R isolates. Extending our analysis to 1,961 isolates with minimum inhibitory concentrations (MICs) revealed thatmmpR5-disrupted isolates had a median BDQ MIC of 0.25 mg/L, compared to the wild-type median of 0.06 mg/L. By matchingmmpR5-disrupted isolates with phylogenetically close control isolates without the disruption, we were able to estimate the impact on MIC of individual mutations. In conclusion, as the MIC increase borders the ECOFF threshold for BDQ-R, we recommend the continued use of MICs and detection of MmpR5 truncations to identify modest shifts in BDQ-R.
Selective consolidation of learning and memory via recall-gated plasticity
Authors: Lindsey Jack , Litwin-Kumar Ashok 
Published: December 2022

AbstractIn a variety of species and behavioral contexts, learning and memory formation recruits two neural systems, with initial plasticity in one system being consolidated into the other over time. Moreover, consolidation is known to be selective; that is, some experiences are more likely to be consolidated into long-term memory than others. Here, we propose and analyze a model that captures common computational principles underlying such phenomena. The key component of this model is a mechanism by which a long-term learning and memory system prioritizes the storage of synaptic changes that are consistent with prior updates to the short-term system. This mechanism, which we refer to as recall-gated consolidation, has the effect of shielding long-term memory from spurious synaptic changes, enabling it to focus on reliable signals in the environment. We describe neural circuit implementations of this model for different types of learning problems, including supervised learning, reinforcement learning, and autoassociative memory storage. These implementations involve synaptic plasticity rules modulated by factors such as prediction accuracy, decision confidence, or familiarity. We then develop an analytical theory of the learning and memory performance of the model, in comparison to alternatives relying only on synapse-local consolidation mechanisms. We find that recall-gated consolidation provides significant advantages, substantially amplifying the signal-to-noise ratio with which memories can be stored in noisy environments. We show that recall-gated consolidation gives rise to a number of phenomena that are present in behavioral learning paradigms, including spaced learning effects, task-dependent rates of consolidation, and differing neural representations in short- and long-term pathways.
Unveiling the time course of visual stabilization through human electrophysiology
Authors: Chung Yong Hoon , Stoermer Viola S. 
Published: December 2022

SummaryPositions of objects are coded relative to their surroundings, presumably providing visual stability even when we move our eyes around a visual scene. But when does this perceived stability of objects arise? Here we use a visual illusion, the frame-induced position shift, and measure electrophysiological activity elicited by an object whose perceived position is either shifted due to a surrounding frame or not, thus dissociating perceived and physical locations. We found that early visually-evoked responses were sensitive to physical location information earlier in time (∼70ms) than perceived location information (∼140ms). Furthermore, we show that location information can be reliably decoded across physical and perceived locations during the later time interval (140-180ms) but not during the earlier time interval (70-110ms). Together these results suggest that visual stability of objects emerges relatively late and is thus dependent on recurrent feedback from higher processing stages.