bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-inflammatory SARS-CoV-2 T cell immunity in asymptomatic seronegative Kenyan adults
Authors: Samandari Taraz , Ongalo Joshua , McCarthy Kim , Biegon Richard K. , Madiega Philister , Mithika Anne , Orinda Joseph , Mboya Grace M. , Mwaura Patrick , Anzala Omu , Onyango Clayton , Oluoch Fredrick O. , Osoro Eric , Dutertre Charles-Antoine , Tan Nicole , Hang Shou Kit , Hariharaputran Smrithi , Lye David C , Herman-Roloff Amy , Bert Nina Le , Bertoletti Antonio 
Published: February 2023

AbstractAntibodies are used to estimate prevalence of past infection. However, T cell responses against SARS-CoV-2 may more accurately define prevalence because SARS-CoV-2-specific antibodies wane. In November-December 2021, we studied serological and cellular immune responses in residents of rural Kenya who had not experienced any respiratory symptom nor had contact with COVID-19 cases. Among participants we detected anti-spike antibodies in 41.0% and T cell responses against ≥2 SARS-CoV-2 proteins in 82.5%, which implies that serosurveys underestimate SARS-CoV-2 prevalence in settings where asymptomatic infections prevail. Distinct from cellular immunity in European and Asian COVID-19 convalescents, strong T cell immunogenicity was observed against viral accessory proteins in these asymptomatic Africans, as well as a higher IL-10/IFN-γ ratio cytokine profile, suggesting that environmental or genetic factors modulate pro-inflammatory responses.FundingU.S. Centers for Disease Control and Prevention, Division of Global Health Protection. Singapore Ministry of Health’s National Medical Research Council under its COVID-19 Research Fund (COVID19RF3-0060, COVID19RF-001 and COVID19RF-008) and the Singapore Ministry of Health’s National Medical Research Council MOH-000019 (MOH-StaR17Nov-0001).
Prevalence of anti-SARS-CoV-2 antibodies in people attending the two main Goma markets in the eastern Democratic Republic of Congo
Authors: Prudence Mitangala Ndeba , Léonid Irenge Mwana Wa Bene , Edgar Musubao Tsongo , Bosco Kahindo Mbeva Jean , Patrick Ayonga Ndeba , Israël Safari Kyembwa , Janvier Kubuya Bonane , Edmon Ntabe Namegabe , Raphaël Kabangwa Kakongo Senga , Guy Mutombo Ndongala , Ambroise Jérôme , Gala Jean-Luc 
Published: February 2023

AbstractAccording to official data, the Democratic Republic of the Congo (DRC) has a low prevalence of the coronavirus disease 19 (COVID-19) pandemic. The goal of this cross-sectional study was to determine the COVID-19 seroprevalence in people attending Goma’s two largest markets, Kituku and Virunga. This study was conducted between September and November 2021, overlapping by one month with another similar study carried out in a slum of Bukavu, and using the same methodology.COVID-19 unvaccinated participants (n = 796 including 454 vendors and 342 customers, 60% of whom were women) were surveyed. The median age of vendors and customers was 34.2 and 30.1 years, respectively.The crude and adjusted anti-SARS-CoV-2 antibody seroprevalence rates were 70.2% (95 % CI 66.9-73.4%) and 98.8% (95% CI 94.1-100%), respectively, with no difference between vendors and customers. COVID-19 symptoms were mild or absent in 58.9% and 41.1% of participants with anti-SARS-CoV-2 antibodies respectively. COVID-19 did not require hospitalisation for any of the seropositive participants.These findings are consistent with those reported in Bukavu. They confirm that SARS-CoV-2 spread without causing severe symptoms in densely populated settlements and markets, and suggest that many COVID-19 cases went unreported. Based on these results, relevance of an untargeted hypothetical vaccination programme in these communities should be questioned.
Fixel-based analysis reveals macrostructural white matter changes associated with tau pathology in early stages of Alzheimer’s disease
Authors: Ahmadi Khazar , Pereira Joana B. , van Westen Danielle , Pasternak Ofer , Zhang Fan , Nilsson Markus , Stomrud Erik , Spotorno Nicola , Hansson Oskar 
Published: February 2023

AbstractWhite matter (WM) alterations are commonly found across different stages of Alzheimer’s disease (AD). However, the association between these changes with underlying AD pathology such as amyloid-β (Aβ) and tau deposition is still poorly understood. Hitherto, most studies have assessed WM alterations in AD using diffusion tensor imaging (DTI). Nonetheless, DTI has methodological shortcomings that limit an accurate biological interpretation. To address this limitation, here we applied fixel-based analysis (FBA) to disentangle microscopic differences in fiber density (FD) from macroscopic morphological changes in fiber cross-section (FC) in early stages of AD. We further investigated the associations of FBA metrics with AD pathology and cognitive performance. Additionally, we compared FBA results with other commonly used WM metrics derived from DTI, free-water corrected (FW)-DTI and diffusion kurtosis imaging (DKI). To achieve these goals, we included 224 Aβ-negative and 91 Aβ-positive cognitively unimpaired individuals as well as 78 Aβ-positive patients with mild cognitive impairment (MCI) with diffusion-weighted MRI (dMRI), Aβ-PET and tau-PET scans from the Swedish BioFINDER-2 study. We found that tau-PET uptake in medial temporal regions was associated with macrostructural alterations reflected by reduced FC mainly in the parahippocampal part of the cingulum bundle in Aβ-positive individuals. This tau-related WM alteration was also associated with impaired memory. Interestingly, only FBA metrics were able to capture the association between tau-PET uptake and white matter degeneration. No association was found between global amyloid load and any dMRI metrics. Compared to both cognitively unimpaired groups, MCI patients showed a decrease in all FBA metrics in the entire cingulum bundle, uncinate fasciculus and anterior thalamic radiations. Metrics derived from DKI, and FW-DTI revealed a similar pattern of alterations whereas the spatial extent of WM abnormalities detected by DTI was more widespread. Altogether, our results indicate that early WM alterations in AD are mainly due to macrostructural changes identified by FBA metrics, being more closely associated with tau than Aβ pathology. These findings suggest that future studies assessing the effects of AD pathology in white matter tracts should consider using FBA metrics.
Comparison of synthesized and acquired highb-value diffusion-weighted MRI for detection of prostate cancer
Authors: Kallis Karoline , Conlin Christopher C. , Zhong Allison Y. , Hussain Troy S. , Chatterjee Aritrick , Karczmar Gregory S. , Rakow-Penner Rebecca , Dale Anders , Seibert Tyler 
Published: February 2023

BackgroundHighb-value diffusion-weighted images (DWI) are used for detection of clinically significant prostate cancer (csPCa). To decrease scan time and improve signal-to-noise ratio, highb-value (>1000 s/mm2) images are often synthesized instead of acquired.PurposeQualitatively and quantitatively compare synthesized DWI (sDWI) to acquired (aDWI) for detection of csPCa.Study TypeRetrospectiveSubjects151 consecutive patients who underwent prostate MRI and biopsy.SequenceAxial DWI withb=0, 500, 1000, and 2000 s/mm2using a 3T clinical scanner using a 32-channel phased-array body coilAssessmentWe synthesized DWI forb=2000 s/mm2via extrapolation based on monoexponential decay, usingb=0 andb=500 s/mm2(sDWI500) andb=0,b=500, andb=1000 s/mm2(sDWI1000). Differences between sDWI and aDWI were evaluated within regions of interest (ROIs). The maximum DWI value within each ROI was evaluated for prediction of csPCa. Classification accuracy was also compared to Restriction Spectrum Imaging restriction score (RSIrs), a previously validated biomarker based on multi-exponential DWI.Statistical TestsDiscrimination of csPCa was evaluated via area under the receiver operating characteristic curve (AUC). Statistical significance was assessed using bootstrap difference (two-sided α=0.05).ResultsWithin the prostate, mean ± standard deviation of percent mean differences between sDWI and aDWI signal were -46±35% for sDWI1000and -67±24% for sDWI500. AUC for aDWI, sDWI500,sDWI1000, and RSIrs within the prostate 0.62[95% confidence interval: 0.53, 0.71], 0.63[0.54, 0.72], 0.65[0.56, 0.73] and 0.78[0.71, 0.86], respectively. When considering the whole field of view, classification accuracy and qualitative image quality decreased notably for sDWI compared to aDWI and RSIrs.Data ConclusionsDWI is qualitatively comparable to aDWI within the prostate. However, hyperintense artifacts are introduced with sDWI in the surrounding pelvic tissue that interfere with quantitative cancer detection and might mask metastases. In the prostate, RSIrs yields superior quantitative csPCa detection than sDWI or aDWI.
Discovery of novel microRNA mimic repressors of ribosome biogenesis
Authors: Bryant Carson J. , McCool Mason A. , Rosado-González Gabriela T. , Abriola Laura , Surovtseva Yulia V. , Baserga Susan J. 
Published: February 2023

AbstractWhile microRNAs and other non-coding RNAs are the next frontier of novel regulators of mammalian ribosome biogenesis (RB), a systematic exploration of microRNA-mediated RB regulation has not yet been undertaken. We carried out a high-content screen in MCF10A cells for changes in nucleolar number using a library of 2,603 mature human microRNA mimics. Following a secondary screen for nucleolar rRNA biogenesis inhibition, we identified 72 novel microRNA negative regulators of RB after stringent hit calling. Hits included 27 well-conserved microRNAs present in MirGeneDB, and were enriched for mRNA targets encoding proteins with nucleolar localization or functions in cell cycle regulation. Rigorous selection and validation of a subset of 15 microRNA hits unexpectedly revealed that most of them caused dysregulated pre-rRNA processing, elucidating a novel role for microRNAs in RB regulation. Almost all hits impaired global protein synthesis and upregulatedCDKN1A(p21) levels, while causing diverse effects on RNA Polymerase 1 (RNAP1) transcription and TP53 protein levels. We discovered that the MIR-28 siblings, hsa-miR-28-5p and hsa-miR-708-5p, directly and potently target the ribosomal protein mRNARPS28via tandem primate-specific 3’ UTR binding sites, causing a severe pre-18S pre-rRNA processing defect. Our work illuminates novel microRNA attenuators of RB, forging a promising new path for microRNA mimic chemotherapeutics.Graphical Abstract
ArMo: An Articulated Mesh Approach for Mouse 3D Reconstruction
Authors: Bohnslav James P. , Osman Mohammed Abdal Monium , Jaggi Akshay , Soares Sofia , Weinreb Caleb , Datta Sandeep Robert , Harvey Christopher D. 
Published: February 2023

AbstractCharacterizing animal behavior requires methods to distill 3D movements from video data. Though keypoint tracking has emerged as a widely used solution to this problem, it only provides a limited view of pose, reducing the body of an animal to a sparse set of experimenter-defined points. To more completely capture 3D pose, recent studies have fit 3D mesh models to subjects in image and video data. However, despite the importance of mice as a model organism in neuroscience research, these methods have not been applied to the 3D reconstruction of mouse behavior. Here, we present ArMo, an articulated mesh model of the laboratory mouse, and demonstrate its application to multi-camera recordings of head-fixed mice running on a spherical treadmill. Using an end-to-end gradient based optimization procedure, we fit the shape and pose of a dense 3D mouse model to data-derived keypoint and point cloud observations. The resulting reconstructions capture the shape of the animal’s surface while compactly summarizing its movements as a time series of 3D skeletal joint angles. ArMo therefore provides a novel alternative to the sparse representations of pose more commonly used in neuroscience research.
The thalamic reticular nucleus-lateral habenula circuit regulates depressive-like behaviors in chronic stress and chronic pain
Authors: Xu Xiang , Chen Rui , Wang Xin-Yue , Jia Wen-Bin , Xu Peng-Fei , Liu Xiao-Qing , Zhang Ying , Liu Xin-Feng , Zhang Yan 
Published: February 2023

AbstractChronic stress and chronic pain are two major predisposing factors to trigger depression. Enhanced excitatory input to the lateral habenula (LHb) has been implicated in the pathophysiology of depression. However, the contribution of inhibitory transmission remains elusive. Here, we dissect an inhibitory projection from the sensory thalamic reticular nucleus (sTRN) to LHb, which is activated by acute aversive stimuli. However, chronic restraint stress (CRS) weakens sTRN-LHb synaptic strength, and this synaptic attenuation is indispensable for CRS-induced LHb neural hyperactivity and depression onset. Moreover, artificially inhibiting sTRN-LHb circuit induces depressive-like behaviors in healthy mice, while enhancing this circuit relieves depression induced by both chronic stress and chronic pain. Intriguingly, neither neuropathic pain nor comorbid pain in chronic stress is affected by this pathway. Together, our study demonstrates a novel sTRN-LHb circuit in establishing and modulating depression, thus shedding light on potential therapeutic targets for preventing or managing depression.
Hebbian priming of human spinal motor learning
Authors: Bjørndal Jonas Rud , Beck Mikkel Malling , Jespersen Lasse , Christiansen Lasse , Lundbye-Jensen Jesper 
Published: February 2023

AbstractLearning or relearning of motor skills requires plasticity in relevant neural circuits. Motor recovery following lesions to the corticospinal system can be augmented through neuromodulation techniques targeting the affected or compensatory neural circuits. By repeatedly pairing transcranial magnetic stimulation of the primary motor cortex (M1) and motoneuronal electrical stimulation (i.e., paired corticomotoneuronal stimulation, PCMS) timed to arrive at the corticomotoneuronal (CM) synapses in close temporal proximity, spike-timing-dependent bidirectional changes in CM transmission can be induced in humans (Taylor & Martin, 2009). PCMS-induced increases in CM transmission have been demonstrated to transiently improve motor control in patients with spinal cord injury (Bunday & Perez 2012), whereas effects on the malleability of neural circuits are entirely unexplored. We hypothesized that PCMS can prime mechanisms of subsequent motor learning exclusively when directed to the neural circuitry underpinning the motor behavior. In three experiments, we provide the first evidence (‘Experiment I’) and a double-blinded, sham-controlled replication (‘Experiment II’) that PCMS targeting the spinal CM synapses can prime subsequent learning of rapid finger movements relying on spinal neuroplasticity. Finally, we demonstrate that the effects of PCMS are circuit-specific and bidirectional. When PCMS was timed to arrive at a facilitatory interval in M1 but an inhibitory interval at the CM synapses subsequent learning was transiently impeded (‘Experiment III’). Taken together, our results provide proof-of-principle that non-invasively induced plasticity governed by Hebbian learning rules interacts with experience-dependent plasticity in the spinal cord with positive implications for motor learning. Our results offer a mechanistic rationale for priming sensorimotor training with individualized PCMS to enhance the effects of motor practice in neurorehabilitation.HighlightsPaired corticomotoneuronal stimulations (PCMS) promote ballistic motor learning and facilitate corticospinal excitability compared to rest and sham protocols.A double-blinded sham experiment replicates priming effects of PCMS on ballistic motor learning and demonstrates long-term benefits of combined PCMS and motor practice.The facilitating effect of PCMS on ballistic motor learning is circuit-specific with superior effects on ballistic motor learning after facilitating PCMS compared to control protocols.
Single-cell transcriptome analysis on the anatomic positional heterogeneity of pig skin
Authors: Zou Qin , Yuan Rong , Zhang Yu , Wang Yifei , Zheng Ting , Shi Rui , Zhang Mei , Li Yujing , Fei Kaixin , Feng Ran , Pan Binyun , Zhang Xinyue , Gong Zhengyin , Zhu Li , Tang Guoqing , Li Mingzhou , Li Xuewei , Jiang Yanzhi 
Published: February 2023

AbstractDifferent anatomic locations of the body skin dermis come from different origins, and its positional hereditary information can be maintained in adults, while highly resolvable cellular specialization is less well characterized in different anatomical regions. Pig is regarded as excellent model for human research in view of its similar physiology to human. In this study, we performed single-cell RNA sequencing of six different anatomical skin regions from the Chenghua pig with superior skin thickness trait. We obtained 215,274 cells, representing seven cell types, among which we primarily characterized the heterogeneity of smooth muscle cells, endothelial cells and fibroblasts. We identified several phenotypes of smooth muscle cell and endothelial cell and presented genes expression of pathways such as the immune response in different skin regions. By comparing differentially expressed fibroblast genes among different skin regions, we considered TNN, COL11A1, and INHBA as candidate genes for facilitating ECM accumulation. These findings of heterogeneity in the main three cell types from different anatomic skin sites will contribute to a better understanding of hereditary information and places the potential focus on skin generation, transmission and transplantation, paving the foundation for human skin priming.
The differentiation and integration of the hippocampal dorsoventral axis are controlled by two nuclear receptor genes
Authors: Yang Xiong , Wan Rong , Liu Zhiwen , Feng Su , Yang Jiaxin , Jing Naihe , Tang Ke 
Published: February 2023

AbstractThe hippocampus executes crucial functions from declarative memory to adaptive behaviors associated with cognition and emotion. However, the mechanisms of how morphogenesis and functions along the hippocampal dorsoventral axis are differentiated and integrated are still largely unclear. Here, we show thatNr2f1andNr2f2genes are distinctively expressed in the dorsal and ventral hippocampus, respectively. The loss ofNr2f2results in ectopic CA1/CA3 domains in the ventral hippocampus. The deficiency ofNr2f1leads to the failed specification of dorsal CA1, among which there are place cells. The deletion of bothNr2fgenes causes almost agenesis of the hippocampus with abnormalities of trisynaptic circuit and adult neurogenesis. Moreover,Nr2f1/2may cooperate to guarantee appropriate morphogenesis and function of the hippocampus by regulating theLhx5-Lhx2axis. Our findings revealed a novel mechanism thatNr2f1andNr2f2converge to govern the differentiation and integration of distinct characteristics of the hippocampus in mice.
Wolbachia has subtle effects on thermal preference in highly inbred Drosophila melanogaster which vary with life stage and environmental conditions
Authors: Strunov Anton , Schoenherr Charlotte , Kapun Martin 
Published: February 2023

AbstractTemperature fluctuations are challenging for ectotherms which are not able to regulate body temperature by physiological means and thus have to adjust their thermal environment via behavior. However, little is yet known about whether microbial symbionts influence thermal preference (Tp) in ectotherms by modulating their physiology. Several recent studies have demonstrated substantial effects ofWolbachiainfections on hostTpin differentDrosophilaspecies. These data indicate that the direction and strength of thermal preference variation is strongly dependent on host and symbiont genotypes and highly variable among studies. By employing highly controlled experiments, we investigated the impact of several environmental factors including humidity, food quality, light exposure, and experimental setup that may influenceTpmeasurements in adultDrosophila melanogasterflies. Additionally, we assessed the effects ofWolbachiainfection onTpofDrosophilaat different developmental stages, which has not been done before. We find only subtle effects ofWolbachiaon hostTpwhich are strongly affected by experimental variation in adult, but not during juvenile life stages. Our in-depth analyses show that environmental variation has a substantial influence onTpwhich demonstrates the necessity of careful experimental design and cautious interpretations ofTpmeasurements together with a thorough description of the methods and equipment used to conduct behavioral studies.
Structure-guided inhibition of the cancer DNA-mutating enzyme APOBEC3A
Authors: Harjes Stefan , Kurup Harikrishnan M. , Rieffer Amanda E. , Bayarjargal Maitsetseg , Filitcheva Jana , Su Yongdong , Hale Tracy K. , Filichev Vyacheslav V. , Harjes Elena , Harris Reuben S. , Jameson Geoffrey B. 
Published: February 2023

ABSTRACTThe normally antiviral enzyme APOBEC3A1-4is an endogenous mutagen in many different human cancers5-7, where it becomes hijacked to fuel tumor evolvability. APOBEC3A’s single-stranded DNA C-to-U editing activity1, 8results in multiple mutagenic outcomes including signature single-base substitution mutations (isolated and clustered), DNA breakage, and larger-scale chromosomal aberrations5-7. Transgenic expression in mice demonstrates its tumorigenic potential9. APOBEC3A inhibitors may therefore comprise a novel class of anticancer agents that work by blocking mutagenesis, preventing tumor evolvability, and lessening detrimental outcomes such as drug resistance and metastasis. Here we reveal the structural basis of competitive inhibition of wildtype APOBEC3A by hairpin DNA bearing 2’-deoxy-5-fluorozebularine in place of the cytidine in the TC recognition motif that is part of a three-nucleotide loop. The nuclease-resistant phosphorothioated derivatives of these inhibitors maintain nanomolarin vitropotency against APOBEC3A, localize to the cell nucleus, and block APOBEC3A activity in human cells. These results combine to suggest roles for these inhibitors to study A3A activity in living cells, potentially as conjuvants, leading toward next-generation, combinatorial anti-mutator and anti-cancer therapies.
Prefronto-subcortical hypoconnectivity in schizophrenia: translation of critical pathways for symptom-related functions in nonhuman primates
Authors: Yahata Noriaki , Hirabayashi Toshiyuki , Minamimoto Takafumi 
Published: February 2023

AbstractRecent advances in genetic neuromodulation technology have enabled circuit-specific interventions in nonhuman primates (NHPs), thereby revealing the causal functions of specific neural circuits. Going forward, an important step is to use these findings to better understand neuropsychiatric and neurological disorders in humans, in which alterations in functional connectivity between brain regions are demonstrated. We recently identified the causal roles of the pathways from the dorsolateral prefrontal cortex (DLPFC) to the lateral part of the mediodorsal thalamic nucleus (MDl) and dorsal caudate nucleus (dCD) in working memory and decision-making, respectively. In the present study, we examined the resting-state functional connectivity of these two prefronto-subcortical circuits in healthy controls (HCs) and patients with various neuropsychiatric disorders including schizophrenia (SCZ), major depressive disorder (MDD), and autism spectrum disorders (ASD) in humans. We found that the functional connectivity of two pathways, DLPFC-MDl and DLPFC-dCD, was significantly reduced in the SCZ groups compared to HCs; however, this hypoconnectivity was not observed in the ASD or MDD groups, suggesting a disease-specific profile of altered prefronto-subcortical connectivity at rest. These results suggest that causal findings of pathway-specific functions revealed in NHPs can be effectively translated to identify the altered connectivity in neuropsychiatric disorders with related symptoms in humans.