bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults
Authors: Carr Edward J , Townsley Hermaleigh , Wu Mary Y , Wilkinson Katalin A , Hobson Philip S , Levi Dina , Namjou Sina , Mears Harriet V , Hobbs Agnieszka , Ragno Martina , Herman Lou S , Harvey Ruth , Bailey Chris , Fowler Ashley S , Hatipoglu Emine , Ngai Yenting , Clayton Bobbi , Miah Murad , Bawumia Philip , Miranda Mauro , Smith Callie , Sawyer Chelsea , Kelly Gavin , Mahalingasivam Viyaasan , Zheng Bang , Evans Stephen JW , Libri Vincenzo , Riddell Andrew , Nicod Jerome , O’Reilly Nicola , Howell Michael , Williams Bryan , Wilkinson Robert J , Kassiotis George , Swanton Charles , Gandhi Sonia , Beale Rupert CL , Bauer David LV , Wall Emma C 
Published: May 2023

ABSTRACTHeterogeneity in SARS-CoV-2 vaccine responses is not understood. Here, we identify four patterns of live-virus neutralizing antibody responses: individuals with hybrid immunity (with confirmed prior infection); rare individuals with low responses (paucity of S1-binding antibodies); and surprisingly, two further groups with distinct serological repertoires. One group – broad responders – neutralize a range of SARS-CoV-2 variants, whereas the other – narrow responders – neutralize fewer, less divergent variants. This heterogeneity does not correlate with Ancestral S1-binding antibody, rather the quality of the serological response. Furthermore, IgDlowCD27-CD137+B cells and CCR6+CD4+T cells are enriched in broad responders before dose 3. Notably, broad responders have significantly longer infection-free time after their third dose. Understanding the control and persistence of these serological profiles could allow personalized approaches to enhance serological breadth after vaccination.
Inherited CDA-I disease: anemia-associated mutations disrupt CDIN1-Codanin1 complex
Authors: Stojaspal Martin , Brom Tomáš , Nečasová Ivona , Janovič Tomáš , Veverka Pavel , Uhrík Lukáš , Hernychova Lenka , Hofr Ctirad 
Published: May 2023

AbstractCongenital dyserythropoietic anemia type I (CDA-I) is a rare hereditary disease characterized by ineffective erythropoiesis, spongy heterochromatin of erythroblasts, and associated mutations in two proteins – Codanin1 and CDIN1. Codanin1 regulates nucleosome assembly through histone chaperone ASF1. The function of recently discovered CDIN1 remains unknown, but CDIN1 has been known to interact directly with the C-terminus of Codanin1. Despite the critical role of identified mutations in Codanin1 and CDIN1, the effects of CDA-I-related mutations at the molecular level have not been elucidated. Here, we determine how low-resolution structural data align with predicted models of CDIN1, Codanin1 C-terminus, and their complex. We define that CDIN1 and Codanin1 assemble with 1:1 stoichiometry and bind with low nanomolar binding affinity. We identify essential interacting regions of CDIN1 and Codanin1. We found that CDA-I-associated mutations disrupt CDIN1-Codanin1 binding, suggesting a potential molecular mechanism underlying the CDA-I disease.HighlightsCDA-I-associated proteins CDIN1 and Codanin1Cterm bind in equimolar ratio with nanomolar affinity.Full-length CDIN1 preferentially forms dimers, Codanin1Cterm monomers.Identified interacting regions of CDIN1 and Codanin1Cterm contain mutations associated with CDA-I disease.CDA-I-related mutations impair binding of CDIN1 and Codanin1Cterm suggesting a potential molecular mechanism underlying the disease.Graphical Abstract
Internal Ribosome Entry Sites act as Effector Domain in linear and circular antisense long non-coding SINEUP RNAs
Authors: D’Agostino Sabrina , Tettey-Matey Abraham , Volpe Massimiliano , Pierattini Bianca , Ansaloni Federico , Lau Pierre , Bon Carlotta , Peruzzo Omar , Braccia Clarissa , Armirotti Andrea , Scarpato Margherita , Damiani Devid , Carlo Valerio Di , Broglia Laura , Bechara Elias , Tartaglia Gian Gaetano , Carninci Piero , Santoro Claudio , Persichetti Francesca , Pandolfini Luca , Espinoza Stefano , Zucchelli Silvia , Sanges Remo , Gustincich Stefano 
Published: May 2023

SummarySINEUPs are antisense long non-coding RNAs that enhance translation of overlapping sense mRNAs through the activity of two domains: aSINEB2 sequenceUP-regulating translation (Effector Domain, ED) and an antisense region providing target specificity (Binding Domain, BD). In this study, we demonstrate that the invSINEB2 sequence from the natural SINEUPAS Uchl1RNA is an Internal Ribosomal Entry Site (IRES) when acting incisand that known viral and cellular IRES sequences can act as Effector Domain in synthetic SINEUPs.To identify natural IRES-containing, non-coding RNAs with SINEUP-like activity, we focused on circular RNAs showing that the non-codingcirc5533, transcribed from thec-myc locus, enhances endogenous protein expression of its targetPX Domain Containing Serine/Threonine Kinase Like(Pxk)by increasing mRNA association to polysomes.In summary, this study shows that natural and synthetic SINEUPs include linear and circular transcripts with an embedded IRES sequence as ED.
Arrive and wait: inactive bacterial taxa contribute to perceived soil microbiome resilience after a multidecadal press disturbance
Authors: Barnett Samuel E. , Shade Ashley 
Published: May 2023

AbstractLong-term (press) disturbances like the climate crisis and other anthropogenic pressures are fundamentally altering ecosystems and their functions. Many critical ecosystem functions, such as biogeochemical cycling, are facilitated by microbial communities. Understanding the functional consequences of microbiome responses to press disturbances requires ongoing observations of the active populations that contribute functions. This study leverages a 7-year time series of a 60-year-old coal seam fire (Centralia, Pennsylvania, USA) to examine the resilience of soil bacterial microbiomes to a press disturbance. Using 16S rRNA and 16S rRNA gene amplicon sequencing, we assessed the interannual dynamics of the active subset and the “whole” bacterial community. Contrary to our hypothesis, the whole communities demonstrated greater resilience than active subsets, suggesting that inactive members contributed to overall resilience. Thus, in addition to selection mechanisms of active populations, perceived microbiome resilience is also supported by mechanisms of dispersal, persistence, and revival from the local dormant pool.
Characterization ofB646L(p72) gene and the resistance pattern of African swine fever Virus tolerant to indigenous Doom Pig breeds of India
Authors: Das Pranab Jyoti , Sonowal Joyshikh , Sengar Gyanendra Singh , Pegu Seema Rani , Deb Rajib , Kumar Satish , Banik Santanu , Rajkhowa Swaraj , Gupta Vivek Kumar 
Published: May 2023

AbstractAfrican Swine Fever (ASF) has affected all pig breeds in North-East India since 2020, except Doom pigs, a unique indigenous breed from Assam and the closest progenitor to Indian wild pigs, resulting in significant economic losses for pig farmers in the region. Based on the complete sequences of theB646L(p72) gene, it has been determined that the virus responsible for the outbreak is ASFV genotype II. The further characterization of three complete sequences of theB646L(p72) gene established 100% identical with other existing sequences of different parts of the world as well as confirmed that there is no co-circulation of different genotypes of ASFV in India except genotype II. Present studies also corroborate thatMYD88, LDHBandIFIT1were important genes of the immune system involved in the pathogenesis of ASFV. The differential expression patterns of these genes in ASFV-infected survived, and healthy Doom breed pigs, compared to healthy control pigs, were studied to distinguish the expression pattern at different stages. The hardiness and ability of the Doom pig to withstand common pig diseases, along with its genetic resemblance to wild pigs, make it an ideal candidate for studying tolerance to ASFV infection. So, the present study investigates the natural resistance to ASF in Doom pigs from an endemic area in North-East India to support the proposition that Doom pigs can co-exist with virulent ASFVs recently break in North-East India. The results of this study also provide important molecular insights into the regulation of the ASFV-tolerant gene.ImportanceStudying the natural resistance to African Swine Fever (ASF) in Doom pigs from North-East India holds crucial importance. ASF has inflicted significant economic losses on pig farmers in the region, necessitating the identification and comprehension of factors contributing to resistance and tolerance in specific pig breeds such as Doom pigs. Understanding the molecular mechanisms and genetic factors associated with ASFV tolerance could help in breeding programs and the selection of resilient pig breeds, ultimately aiding in disease control efforts.
Type-2 diabetes alters hippocampal neural oscillations and disrupts synchrony between hippocampus and cortex
Authors: Rabiller Gratianne , Ip Zachary , Zarrabian Shahram , Zhang Hongxia , Sato Yoshimichi , Yazdan-Shahmorad Azadeh , Liu Jialing 
Published: May 2023

AbstractType 2 diabetes mellitus (T2DM) increases the risk of neurological diseases, yet how brain oscillations change as age and T2DM interact is not well characterized. To delineate the age and diabetic effect on neurophysiology, we recorded local field potentials with multichannel electrodes spanning the somatosensory cortex and hippocampus (HPC) under urethane anesthesia in diabetic and normoglycemic control mice, at 200 and 400 days of age. We analyzed the signal power of brain oscillations, brain state, sharp wave associate ripples (SPW-Rs), and functional connectivity between the cortex and HPC. We found that while both age and T2DM were correlated with a breakdown in long-range functional connectivity and reduced neurogenesis in the dentate gyrus and subventricular zone, T2DM further slowed brain oscillations and reduced theta-gamma coupling. Age and T2DM also prolonged the duration of SPW-Rs and increased gamma power during SPW-R phase. Our results have identified potential electrophysiological substrates of hippocampal changes associated with T2DM and age. The perturbed brain oscillation features and diminished neurogenesis may underlie T2DM-accelerated cognitive impairment.
HTLV-1 reverse transcriptase homology model provides structural basis for sensitivity to existing nucleoside/nucleotide reverse transcriptase inhibitors
Authors: Tardiota Nicolas , Jaberolansar Noushin , Lackenby Julia A. , Chappell Keith J. , O’Donnell Jake S. 
Published: May 2023

AbstractThe human T-lymphotropic virus type 1 (HTLV-1) infects millions of people globally and is endemic to various resource-limited regions. Infections persist for life and are associated with increased susceptibility to opportunistic infections and severe diseases including adult T cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy-tropical spastic paraparesis (HAM-TSP). No HTLV-1-specific anti-retrovirals have been developed and it is unclear whether existing anti-retrovirals developed for treatment of human immunodeficiency virus (HIV) have efficacy against HTLV-1. To understand the structural basis for therapeutic binding, homology modelling and machine learning were used to develop a structural model of the HTLV-1 reverse transcriptase. With this, molecular docking experiments using a panel of FDA-approved inhibitors of viral reverse transcriptases to assess their capacity for binding, and in turn, inhibition. Importantly, nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) but not non-nucleoside reverse transcriptase inhibitors (NNRTIs) were capable of binding the HTLV-1 reverse transcriptase, with similar affinity to HIV-1 reverse transcriptase. By strengthening the rationale for clinical testing of therapies such as tenofovir alafenamide, zidovudine, lamivudine, and azvudine for treatment of HTLV-1, this study has demonstrated the power ofin silicostructural biology approaches in drug design and therapeutic testing.
ARID1A governs the silencing of sex-linked transcription during male meiosis in the mouse
Authors: Menon Debashish U. , Chakraborty Prabuddha , Murcia Noel , Magnuson Terry 
Published: May 2023

AbstractWe present evidence implicating the BAF (BRG1/BRM Associated Factor) chromatin remodeler in meiotic sex chromosome inactivation (MSCI). By immunofluorescence (IF), the putative BAF DNA binding subunit, ARID1A (AT-rich Interaction Domain 1a), appeared enriched on the male sex chromosomes during diplonema of meiosis I. Those germ cells showing a Cre-induced loss of ARID1A were arrested in pachynema and failed to repress sex-linked genes, indicating a defective MSCI. Consistent with this defect, mutant sex chromosomes displayed an abnormal presence of elongating RNA polymerase II coupled with an overall increase in chromatin accessibility detectable by ATAC-seq. By investigating potential mechanisms underlying these anomalies, we identified a role for ARID1A in promoting the preferential enrichment of the histone variant, H3.3, on the sex chromosomes, a known hallmark of MSCI. Without ARID1A, the sex chromosomes appeared depleted of H3.3 at levels resembling autosomes. Higher resolution analyses by CUT&RUN revealed shifts in sex-linked H3.3 associations from discrete intergenic sites and broader gene-body domains to promoters in response to the loss of ARID1A. Several sex-linked sites displayed ectopic H3.3 occupancy that did not co-localize with DMC1 (DNA Meiotic Recombinase 1). This observation suggests a requirement for ARID1A in DMC1 localization to the asynapsed sex chromatids. We conclude that ARID1A-directed H3.3 localization influences meiotic sex chromosome gene regulation and DNA repair.
Neuroanatomical and functional dissociations between variably present anterior lateral prefrontal sulci
Authors: Willbrand Ethan H. , Bunge Silvia A. , Weiner Kevin S. 
Published: May 2023

AbstractThe lateral prefrontal cortex (LPFC) is an evolutionarily expanded region in humans that is critical for numerous complex functions, many of which are largely hominoid-specific. While recent work shows that the presence or absence of specific sulci in anterior LPFC is associated with cognitive performance across age groups, it is unknown whether the presence of these structures relates to individual differences in the functional organization of LPFC. To fill this gap in knowledge, we leveraged multimodal neuroimaging data from 72 young adult humans aged 22-36 and show that dorsal and ventral components of the paraintermediate frontal sulcus (pimfs) present distinct morphological (surface area), architectural (thickness and myelination), and functional (resting-state connectivity networks) properties. We further contextualize the pimfs components within classic and modern cortical parcellations. Taken together, the dorsal and ventral pimfs components mark transitions in anatomy and function in LPFC, across metrics and parcellations. These results emphasize that the pimfs is a critical structure to consider when examining individual differences in the anatomical and functional organization of LPFC and highlight the importance of considering individual anatomy when investigating structural and functional features of the cortex.
An Alzheimer’s disease risk variant inTTC3modifies the actin cytoskeleton organization and the PI3K-Akt signaling pathway in iPSC-derived forebrain neurons
Authors: Cukier Holly N. , Duarte Carolina L. , Laverde-Paz Mayra J. , Simon Shaina A. , Van Booven Derek J. , Miyares Amanda T. , Whitehead Patrice L. , Hamilton-Nelson Kara L. , Adams Larry D. , Carney Regina M. , Cuccaro Michael L. , Vance Jeffery M. , Pericak-Vance Margaret A. , Griswold Anthony J. , Dykxhoorn Derek M. 
Published: May 2023

AbstractA missense variant in thetetratricopeptide repeat domain 3(TTC3) gene (rs377155188, p.S1038C, NM_003316.4:c.3113C>G) was found to segregate with disease in a multigenerational family with late onset Alzheimer’s disease. This variant was introduced into induced pluripotent stem cells (iPSCs) derived from a cognitively intact individual using CRISPR genome editing and the resulting isogenic pair of iPSC lines were differentiated into cortical neurons. Transcriptome analysis showed an enrichment for genes involved in axon guidance, regulation of actin cytoskeleton, and GABAergic synapse. Functional analysis showed that the TTC3 p.S1038C iPSC-derived neuronal progenitor cells had altered 3D morphology and increased migration, while the corresponding neurons had longer neurites, increased branch points, and altered expression levels of synaptic proteins. Pharmacological treatment with small molecules that target the actin cytoskeleton could revert many of these cellular phenotypes, suggesting a central role for actin in mediating the cellular phenotypes associated with the TTC3 p.S1038C variant.HighlightsThe AD risk variant TTC3 p.S1038C reduces the expression levels ofTTC3The variant modifies the expression of AD specific genesBACE1,INPP5F, andUNC5CNeurons with the variant are enriched for genes in the PI3K-Akt pathwayiPSC-derived neurons with the alteration have increased neurite length and branchingThe variant interferes with actin cytoskeleton and is ameliorated by Cytochalasin D
Micromagnetic Stimulation (μMS) Controls Dopamine Release: Anin vivoStudy Using WINCSHarmoni
Authors: Saha Renata , Goyal Abhinav , Yuen Jason , Oh Yoonbae , Bloom Robert P. , Benally Onri J. , Wu Kai , Netoff Theoden I. , Low Walter C. , Bennet Kevin E. , Lee Kendall H. , Shin Hojin , Wang Jian-Ping 
Published: May 2023

AbstractObjectiveResearch into the role of neurotransmitters in regulating normal and pathologic brain functions has made significant progress. Yet, clinical trials that aim to improve therapeutic interventions do not take advantage of thein vivochanges in the neurochemistry that occur in real time during disease progression, drug interactions or response to pharmacological, cognitive, behavioral, and neuromodulation therapies. In this work, we used the WINCSHarmonitool to study the real timein vivochanges in dopamine release in rodent brains for the micromagnetic neuromodulation therapy.ApproachAlthough still in its infancy, micromagnetic stimulation (μMS) using micro-meter sized coils or microcoils (μcoils) has shown incredible promise in spatially selective, galvanic contact free and highly focal neuromodulation. These μcoils are powered by a time-varying current which generates a magnetic field. As per Faraday’s Laws of Electromagnetic Induction, this magnetic field induces an electric field in a conducting medium (here, the brain tissues). We used a solenoidal-shaped μcoil to stimulate the medial forebrain bundle (MFB) of the rodent brainin vivo. The evokedin vivodopamine releases in the striatum were tracked in real time by carbon fiber microelectrodes (CFM) using fast scan cyclic voltammetry (FSCV).ResultsOur experiments report that μcoils can successfully activate the MFB in rodent brains, triggering dopamine releasein vivo. We further show that the successful release of dopamine upon micromagnetic stimulation is dependent on the orientation of the μcoil. Furthermore, varied intensities of μMS can control the concentration of dopamine releases in the striatum.SignificanceThis work helps us better understand the brain and its conditions arising from a new therapeutic intervention, like μMS, at the level of neurotransmitter release. Despite its early stage, this study potentially paves the path for μMS to enter the clinical world as a precisely controlled and optimized neuromodulation therapy.
Commensal protists in reptiles display flexible host range and adaptation to ectothermic hosts
Authors: Gerrick Elias R. , DeSchepper Leila B. , Mechler Claire M. , Joubert Lydia-Marie , Dunker Freeland , Colston Timothy J. , Howitt Michael R. 
Published: May 2023

AbstractParabasalid protists recently emerged as keystone members of the mammalian microbiota with important effects on their host’s health. However, the prevalence and diversity of parabasalids in wild reptiles and the consequences of captivity and other environmental factors on these symbiotic protists are unknown. Reptiles are ectothermic, and their microbiomes are subject to temperature fluctuations, such as those driven by climate change. Thus, conservation efforts for threatened reptile species may benefit from understanding how shifts in temperature and captive breeding influence the microbiota, including parabasalids, to impact host fitness and disease susceptibility. Here, we surveyed intestinal parabasalids in a cohort of wild reptiles across three continents and compared these to captive animals. Reptiles harbor surprisingly few species of parabasalids compared to mammals, but these protists exhibited a flexible host-range, suggesting specific adaptations to reptilian social structures and microbiota transmission. Furthermore, reptile-associated parabasalids are adapted to wide temperature ranges, although colder temperatures significantly altered the protist transcriptomes, with increased expression of genes associated with detrimental interactions with the host. Our findings establish that parabasalids are widely distributed in the microbiota of wild and captive reptiles and highlight how these protists respond to temperature swings encountered in their ectothermic hosts.
The Crucial Role of CTCF in Mitotic Progression during Early Development of Sea Urchin
Authors: Watanabe Kaichi , Fujita Megumi , Okamoto Kazuko , Yoshioka Hajime , Moriwaki Miki , Tagashira Hideki , Awazu Akinori , Yamamoto Takashi , Sakamoto Naoaki 
Published: May 2023

AbstractCCCTC-binding factor (CTCF), an insulator protein with 11 zinc fingers, is enriched at the boundaries of topologically associated domains (TADs) in eukaryotic genomes. In this study, we isolated and analyzed the cDNAs encoding HpCTCF, the CTCF homolog in the sea urchinHemicentrotus pulcherrimus, to investigate its expression patterns and functions during early development of sea urchin. HpCTCF contains nine zinc fingers corresponding to fingers 2–10 of the vertebrate CTCF. The expression pattern analysis revealed thatHpCTCFmRNA was detected at all developmental stages and in the entire embryo. Upon expressing the HpCTCF-GFP fusion protein in early embryos, we observed its uniform distribution within interphase nuclei. However, during mitosis, it disappeared from the chromosomes and subsequently reassembled on the chromosome during telophase. Moreover, the morpholino-mediated knockdown of HpCTCF resulted in mitotic arrest during the morula-to-blastula stage. Most of the arrested chromosomes were not phospholylated at serine 10 of histone H3, indicating that mitosis was arrested at the telophase by HpCTCF depletion. Furthermore, impaired sister chromatid segregation was observed using time-lapse imaging of HpCTCF-knockdown embryos. Thus, HpCTCF is essential for mitotic progression during the early development of sea urchins, especially during the telophase-to-interphase transition. However, the normal development of pluteus larvae in CRISPR-mediated HpCTCF knockout embryos suggests that disruption of zygotic HpCTCF expression has little effect on embryonic and larval development.