bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of SARS-CoV-2 during the first year of the COVID-19 pandemic in Northwestern Argentina
Authors: Zambrana Montaño Romina , Culasso Andrés Carlos Alberto , Fernández Franco , Marquez Nathalie , Debat Humberto , Salmerón Mariana , Zamora Ana María , Ruíz de Huidobro Gustavo , Costas Dardo , Alabarse Graciela , Charre Miguel Alejandro , Fridman Ariel David , Mamani Claudia , Vaca Fabiana , Maza Diaz Claudia , Raskovsky Viviana , Lavaque Esteban , Lesser Veronica , Cajal Pamela , Agüero Fernanda , Calvente Cintia , Torres Carolina , Viegas Mariana 
Published: July 2022

ABSTRACTStudies about the evolution of SARS-CoV-2 lineages in different backgrounds such as naive populations, are still scarce, especially from South America. The aim of this work was to study the introduction and diversification pattern of SARS-CoV-2 during the first year of the COVID-19 pandemic in the Northwestern Argentina (NWA) region and to analyze the evolutionary dynamics of the main lineages found. In this study, we analyzed a total of 260 SARS-CoV-2 whole-genome sequences from Argentina, belonging to the Provinces of Jujuy, Salta and Tucumán, from March 31st, 2020, to May 22nd, 2021, which covered the full first wave and the early second wave of the COVID-19 pandemic in Argentina. In the first wave, eight lineages were identified: B.1.499 (76.9%), followed by N.5 (10.2%), B.1.1.274 (3.7%), B.1.1.348 (3.7%), B.1 (2.8%), B.1.600 (0.9%), B.1.1.33 (0.9%) and N.3 (0.9%). During the early second wave, the first-wave lineages were displaced by the introduction of variants of concern (VOC) (Alpha, Gamma), or variants of interest (VOI) (Lambda, Zeta, Epsilon) and other lineages with more limited distribution. Phylodynamic analyses of the B.1.499 and N.5, the two most prevalent lineages in NWA, revealed that the substitution rate of lineage N.5 (7.9 × 10−4 substitutions per site per year, s/s/y) was a ∼40% faster than that of lineage B.1.499 (5.9 × 10−4 s/s/y), although both are in the same order of magnitude than other non-VOC lineages. No mutations associated with a biological characteristic of importance were observed as signatures markers of the phylogenetic groups established in Northwestern Argentina, however, single sequences in non-VOC lineages did present mutations of biological importance or associated with VOCs as sporadic events, showing that many of these mutations could emerge from circulation in the general population. This study contributed to the knowledge about the evolution of SARS-CoV-2 in a pre-vaccination and without post-exposure immunization period.
Unwilling or Unable? Using 3D tracking to evaluate dogs’ reactions to differing human intentions
Authors: Völter Christoph J. , Lonardo Lucrezia , Steinmann Maud G.G.M. , Ramos Carolina Frizzo , Gerwisch Karoline , Schranz Monique-Theres , Dobernig Iris , Huber Ludwig 
Published: July 2022

AbstractThe extent to which dogs (Canis familiaris) as a domesticated species understand human intentions is still a matter of debate. The unwilling-unable paradigm has been developed to examine whether nonhuman animals are sensitive to intentions underlying human actions. In this paradigm, subjects tended to show more patience toward a human that appears willing but unable to transfer food to them compared to an unwilling (teasing) human. In the present study, we conducted the unwilling-unable paradigm with dogs using a detailed behavioural analysis based on machine-learning driven 3D tracking. Throughout two preregistered experiments, we found evidence, in line with our prediction, that dogs reacted more impatiently to actions signalling unwillingness to transfer food rather than inability. These differences were consistent through two different samples of pet dogs (total N=96) and they were evident also in the machine-learning generated 3D tracking data. Our results, therefore, provide robust evidence that dogs distinguish between similar actions (leading to the same outcome) associated with different intentions. However, their reactions did not lead to any measurable preference for one experimenter over the other in a subsequent transfer phase. We discuss different cognitive mechanisms that might underlie dogs’ performance in this paradigm.
White matter connectivity in uncinate fasciculus accounts for visual attention span in developmental dyslexia
Authors: Zhao Jingjing , Song Zujun , Zhao Yueye , Thiebaut de Schotten Michel , Altarelli Irene , Ramus Franck 
Published: July 2022

AbstractThe present study aimed to investigate the role of connectivity disruptions in two fiber pathways, the uncinate fasciculus (UF) and the frontal aslant tract (FAT), in developmental dyslexia and determine the relationship between the connectivity of these pathways and behavioral performance in children with dyslexia. A total of 26 French children with dyslexia and 31 age-matched control children were included. Spherical deconvolution tractography was used to reconstruct the two fiber pathways. Hindrance-modulated oriented anisotropy (HMOA) was used to measure the connectivity of each fiber pathway in both hemispheres. The boys with dyslexia showed reduced HMOA in the UF compared to control boys, but this difference was not observed in girls. Furthermore, HMOA of the UF correlated with individual differences in the visual attention span in participants with dyslexia. All significant results found in HMOA of the UF were verified in fractional anisotropy (FA) of the UF using standard diffusion imaging model. This study suggests a differential sex effect on the connectivity disruption in the UF in developmental dyslexia. It also indicates that the UF may play an essential role in the visual attention span deficit in developmental dyslexia.Significance StatementThis study presents the first account of connectivity disruption in the uncinate fasciculus in developmental dyslexia. In particular, this connectivity disruption only appears in boys with dyslexia but not in girls with dyslexia. We also show that the connectivity of the uncinate fasciculus accounts for individual differences in the visual attention span in children with dyslexia, expanding the current understanding of the function of the uncinate fasciculus.
Landscape of infection enhancing antibodies in COVID-19 and healthy donors
Authors: Ismanto Hendra S , Xu Zichang , Saputri Dianita S , Wilamowski Jan , Li Songling , Nugraha Dendi K , Horiguchi Yasuhiko , Okada Masato , Arase Hisashi , Standley Daron M 
Published: July 2022

AbstractTo assess the frequency of SARS-CoV-2 infection enhancing antibodies in the general population, we searched over 64 million heavy chain antibody sequences from healthy and COVID-19 patient repertoires for sequences similar to 11 previously reported enhancing antibodies. Although the distribution of sequence identities was similar in COVID-19 and healthy repertoires, the COVID-19 hits were significantly more clonally expanded than healthy hits. Furthermore, among the tested hits, 17 out of 94 from COVID-19, compared with 2 out of 96 from healthy, bound to the enhancing epitope. A total of 6 of the 19 epitope-binding antibodies enhanced ACE2 receptor binding to the spike protein. Together, this study revealed that enhancing antibodies are far more frequent in COVID-19 patients than in healthy donors, but a reservoir of potential enhancing antibodies exists in healthy donors that could potentially mature to actual enhancing antibodies upon infection.
Thick Filament Activation Is Different in Fast and Slow-Twitch Skeletal Muscle
Authors: Gong Henry M. , Ma Weikang , Regnier Michael , Irving Thomas C. 
Published: July 2022

AbstractThe contractile properties of fast-twitch and slow-twitch skeletal muscles are primarily determined by the myosin isoform content and modulated by a variety of sarcomere proteins. X-ray diffraction studies of regulatory mechanisms in muscle contraction have focused predominately on fast-or mixed-fiber muscle with slow muscle being much less studied. Here, we used time-resolved x-ray diffraction to investigate the dynamic behavior of the myofilament proteins in relatively pure slow fiber rat soleus (SOL) and pure fast fiber rat extensor digitorum longus (EDL) muscle during twitch and tetanic contractions at optimal length. During twitch contractions the diffraction signatures indicating a transition in the myosin heads from ordered OFF states, where heads are held close to the thick filament backbone, to disordered ON states, where heads are free to bind to thin filaments, were found in EDL and not in SOL muscle. During tetanic contraction, changes in the disposition of myosin heads as active tension develops is a cooperative process in EDL muscle whereas in SOL muscle this relationship is less cooperative. The observed reduced extensibility of the thick filaments in SOL muscle as compared to EDL muscles indicate a molecular basis for this behavior. These data indicate that for the EDL thick filament activation is a cooperative strain-induced mechano-sensing mechanism, whereas for the SOL thick filament activation has a more graded response. These different approaches to thick filament regulation in fast- and slow-twitch muscles may be adaptations for short duration, strong contractions versus sustained, finely controlled contractions, respectively.Key PointsFast twitch muscle and slow-twitch muscle are optimized for strong, short duration contractions and sustained smaller movements respectively.Structural events (OFF to ON transitions) in the myosin containing thick filaments in fast muscle help determine the timing and strength of contractions but these have not been studied in slow-twitch muscle.The X-ray diffraction signatures of structural OFF to ON transitions are different in fast extensor digitorum longus (EDL) and slow soleus (SOL) muscle, being completely absent during twitches in soleus muscle and blunted during tetanic contractions SOL as compared to EDLCooperative thick filament structural OFF to ON transitions in fast twitch muscle may be an adaptation for rapid and ballistic movements whereas more graded OFF to ON structural transitions in slow-twitch muscle may be an adaptation for slower, finer motions.
Possible role of left–right asymmetry in the sensory system and behavior during adaptation to food-sparse cave environments
Authors: Fernandes Vânia Filipa Lima , Glaser Yannik , Iwashita Motoko , Yoshizawa Masato 
Published: July 2022

AbstractLaterality in relation to behavior and sensory systems is found commonly in a variety of animal taxa. Despite the advantages conferred by laterality (e.g., the startle response and complex motor activities), little is known about the evolution of laterality and its plasticity in response to ecological demands. In the present study, a comparative study model, the Mexican tetra (Astyanax mexicanus), composed of two morphotypes, i.e., riverine surface fish and caved-welling cavefish, was used to address the relationship between environment and laterality. The use of a machine learning-based fish posture detection system and sensory ablation revealed that the left cranial lateral line significantly supports one type of foraging behavior, i.e., vibration attraction behavior, in one cave population. Additionally, left–right asymmetric approaches toward a vibrating rod became symmetrical after fasting in one cave population but not in the other populations. Based on these findings, we propose a model explaining how the observed sensory laterality and behavioral shift could help adaptations in terms of the tradeoff in energy gain and loss during foraging according to differences in food availability among caves.
A synthetic protein-level neural network in mammalian cells
Authors: Chen Zibo , Linton James M. , Zhu Ronghui , Elowitz Michael B. 
Published: July 2022

AbstractArtificial neural networks provide a powerful paradigm for information processing that has transformed diverse fields. Within living cells, genetically encoded synthetic molecular networks could, in principle, harness principles of neural computation to classify molecular signals. Here, we combine de novo designed protein heterodimers and engineered viral proteases to implement a synthetic protein circuit that performs winner-take-all neural network computation. This “perceptein” circuit includes modules that compute weighted sums of input protein concentrations through reversible binding interactions, and allow for self-activation and mutual inhibition of protein components using irreversible proteolytic cleavage reactions. Altogether, these interactions comprise a network of 310 chemical reactions stemming from 8 expressed protein species. The complete system achieves signal classification with tunable decision boundaries in mammalian cells. These results demonstrate how engineered protein-based networks can enable programmable signal classification in living cells.One-Sentence SummaryA synthetic protein circuit that performs winner-take-all neural network computation in mammalian cells
Cystathionine β-synthase gene inactivation dysregulates major urinary protein biogenesis and impairs sexual signaling in mice
Authors: Bretes Ewa , Wróblewski Jacek , Wyszczelska-Rokiel Monika , Jakubowski Hieronim 
Published: July 2022

ABSTRACTReproductive success in mice depends on major urinary proteins (Mup) that facilitate sexual interactions between females and males. Deletion of cystathionine β-synthase (Cbs) gene, a metabolic gene important for homeostasis of one-carbon metabolism, impairs reproduction by causing female infertility in mice. Here we examined Mup biogenesis and sexual signaling inCbs−/−vs.Cbs+/−mice. We found that total urinary Mup protein was significantly reduced in male and femaleCbs−/−vs. Cbs+/−mice. SDS-PAGE/Western blot, ESIMS, and RT-qPCR analyses of the liver, plasma, and urinary proteins identified a male-specific Mup20 inCbs−/−, but notCbs+/−females. As other Mups were significantly reduced, the 18,893 Da Mup20 became the most abundand in urine ofCbs−/−females and males. Effects ofCbsgenotype on 18,645 Da, 18,693 Da, and 18,709 Da Mup species abundance were Mup and sex-specific.Cbs-dependent changes in hepatic Mups and Mup20 expression were similar at the protein and mRNA level. Changes in Mups, but not in Mup20, can be explained by downregulation of hepatic Zhx2 and Ghr receptors inCbs−/−mice. Behavioral testing showed thatCbs+/−females were attracted toCbs+/−but not toCbs−/−male urine.Cbs+/−males did not countermark urine ofCbs−/−males but countermarked urine of otherCbs+/−males and were attracted to urines ofCbs−/−as well asCbs+/−females.Cbs−/−males did not countermark urine ofCbs+/−males but were still attracted to urines ofCbs+/−females. Taken together, these findings show thatCbs, a metabolic gene, plays an important role in the regulation of Mup biogenesis and sexual signaling in mice.
Amplified cortical neural responses as animals learn to use novel activity patterns
Authors: Akitake Bradley , Douglas Hannah M. , LaFosse Paul K. , Beiran Manuel , Deveau Ciana E. , O’Rawe Jonathan , Li Anna J. , Ryan Lauren N. , Duffy Samuel P. , Zhou Zhishang , Deng Yanting , Rajan Kanaka , Histed Mark H. 
Published: July 2022

SummaryCerebral cortex supports representations of the world in patterns of neural activity, used by the brain to make decisions and guide behavior. Past work has found diverse, or limited, changes in the primary sensory cortex in response to learning, suggesting the key computations might occur in downstream regions. Alternatively, sensory cortical changes may be central to learning. We studied cortical learning by using controlled inputs we insert: we trained mice to recognize entirely novel, non-sensory patterns of cortical activity in the primary visual cortex (V1) created by optogenetic stimulation. As animals learned to use these novel patterns, we found their detection abilities improved by an order of magnitude or more. The behavioral change was accompanied by large increases in V1 neural responses to fixed optogenetic input. Neural response amplification to novel optogenetic inputs had little effect on existing visual sensory responses. A recurrent cortical model shows that this amplification can be achieved by a small mean shift in recurrent network synaptic strength. Amplification would seem to be desirable to improve decision-making in a detection task, and therefore these results suggest that adult recurrent cortical plasticity plays a significant role in improving behavioral performance during learning.
High-throughput Genetic Clustering of Type 2 Diabetes Loci Reveals Heterogeneous Mechanistic Pathways of Metabolic Disease
Authors: Kim Hyunkyung , Westerman Kenneth E. , Smith Kirk , Chiou Joshua , Cole Joanne B. , Majarian Timothy , von Grotthuss Marcin , Mercader Josep M. , Kwak Soo Heon , Kim Jaegil , Florez Jose C. , Gaulton Kyle , Manning Alisa K. , Udler Miriam S. 
Published: July 2022

AbstractAims/hypothesisType 2 diabetes (T2D) is highly polygenic and influenced by multiple biological pathways. Rapid expansion in the number of T2D loci can be leveraged to identify such pathways, thus facilitating improved disease management.MethodsWe developed a high-throughput pipeline to enable clustering of T2D loci based on variant-trait associations. Our pipeline extracted summary statistics from genome-wide association studies (GWAS) for T2D and related traits to generate a matrix of 324 variant x 64 trait associations and applied Bayesian Non-negative Factorization (bNMF) to identify genetic components of T2D. We generated cluster-specific polygenic scores and performed regression analysis in an independent cohort (N=25,419) to assess for clinical relevance.ResultsWe identified ten clusters, replicating the five from our prior analysis as well as novel clusters related to beta-cell dysfunction, pronounced insulin secretion, and levels of alkaline phosphatase, lipoprotein-A, and sex hormone-binding globulin. Four clusters related to mechanisms of insulin deficiency, five to insulin resistance, and one had an unclear mechanism. The clusters displayed tissue-specific epigenomic enrichment, notably with the two beta-cell clusters differentially enriched in functional and stressed pancreatic beta-cell states. Additionally, cluster-specific polygenic scores were differentially associated with patient clinical characteristics and outcomes. The pipeline was applied to coronary artery disease and chronic kidney disease, identifying multiple shared genetic pathways with T2D.Conclusions/interpretationOur approach stratifies T2D loci into physiologically meaningful genetic clusters associated with distinct tissues and clinical outcomes. The pipeline allows for efficient updating as additional GWAS become available and can be readily applied to other conditions, facilitating clinical translation of GWAS findings. Software to perform this clustering pipeline is freely available.
Protection of SARS-CoV-2 natural infection against reinfection with the Omicron BA.4 or BA.5 subvariants
Authors: Altarawneh Heba N. , Chemaitelly Hiam , Ayoub Houssein H. , Hasan Mohammad R. , Coyle Peter , Yassine Hadi M. , Al-Khatib Hebah A. , Benslimane Fatiha M. , Al-Kanaani Zaina , Al-Kuwari Einas , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Abdul-Rahim Hanan F. , Nasrallah Gheyath K. , Al-Kuwari Mohamed Ghaith , Butt Adeel A. , Al-Romaihi Hamad Eid , Al-Thani Mohamed H. , Al-Khal Abdullatif , Bertollini Roberto , Tang Patrick , Abu-Raddad Laith J. 
Published: July 2022

AbstractThis study estimates the effectiveness of previous infection with SARS-CoV-2 in preventing reinfection with Omicron BA.4/BA.5 subvariants using a test-negative, case–control study design. Cases (SARS-CoV-2-positive test results) and controls (SARS-CoV-2-negative test results) were matched according to sex, 10-year age group, nationality, comorbid condition count, calendar week of testing, method of testing, and reason for testing. Effectiveness was estimated using the S-gene “target failure” (SGTF) infections between May 7, 2022-July 4, 2022. SGTF status provides a proxy for BA.4/BA.5 infections, considering the negligible incidence of other SGTF variants during the study. Effectiveness was also estimated using all diagnosed infections between June 8, 2022-July 4, 2022, when BA.4/BA.5 dominated incidence. Effectiveness of a previous pre-Omicron infection against symptomatic BA.4/BA.5 reinfection was 15.1% (95% CI: -47.1-50.9%), and against any BA.4/BA.5 reinfection irrespective of symptoms was 28.3% (95% CI: 11.4-41.9%). Effectiveness of a previous Omicron infection against symptomatic BA.4/BA.5 reinfection was 76.1% (95% CI: 54.9-87.3%), and against any BA.4/BA.5 reinfection was 79.7% (95% CI: 74.3-83.9%). Results using all diagnosed infections when BA.4/BA.5 dominated incidence confirmed the same findings. Sensitivity analyses adjusting for vaccination status confirmed study results. Protection of a previous infection against BA.4/BA.5 reinfection was modest when the previous infection involved a pre-Omicron variant, but strong when the previous infection involved the Omicron BA.1 or BA.2 subvariants. Protection of a previous infection against BA.4/BA.5 was lower than that against BA.1/BA.2, consistent with BA.4/BA.5’s greater capacity for immune-system evasion than that of BA.1/BA.2.
Longitudinal decline in striatal dopamine transporter binding in Parkinson’s disease: Associations with apathy and anhedonia
Authors: Costello Harry , Yamamori Yumeya , Reeves Suzanne , Schrag Anette , Howard Robert , Roiser Jonathan P. 
Published: July 2022

SummaryBackgroundMotivational symptoms such as apathy and anhedonia are common in Parkinson’s disease, respond poorly to treatment, and have been hypothesised to share underlying neural mechanisms. Striatal dopaminergic dysfunction is considered central to motivational symptoms in Parkinson’s disease, but the association has never been examined longitudinally. We investigated whether the progression of dopaminergic neurodegeneration was associated with emergent apathy and anhedonia symptoms in Parkinson’s disease.MethodsLongitudinal cohort study of 412 newly diagnosed Parkinson’s disease patients followed over five years as part of the Parkinson’s Progression Markers Initiative (PPMI) cohort. Apathy and anhedonia were measured using a composite score derived from relevant items of the 15-item geriatric depression scale (GDS-15) and part I of the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Dopaminergic neurodegeneration was measured using repeated ioflupane [123-I] single photon emission computed tomography imaging of striatal dopamine transporters (DAT).ResultsLinear mixed-effects modelling across all contemporaneous data points identified a significant negative relationship between striatal DAT specific binding ratio(SBR) and apathy/anhedonia symptoms, which emerged as Parkinson’s disease progressed (interaction: β=-0.09, 95%CI[-0.15 -0.03], p=0.002). Appearance and subsequent worsening of apathy/anhedonia symptoms began on average two years after diagnosis and below a threshold striatal DAT SBR level. The interaction between striatal DAT SBR and time was specific to apathy/anhedonia symptoms, with no evidence of a similar interaction for general depressive symptoms from the GDS-15 (excluding apathy/anhedonia items) (β=-0.06, 95%CI[-0.13 0.01]) or motor symptoms indexed by the MDS-UPDRS part III (β=0.20, 95%CI[-0.25 0.65]).ConclusionThe relationship between the progression of dopaminergic neurodegeneration and emergent apathy/anhedonia symptoms supports a central role for dopaminergic dysfunction in motivational symptoms in Parkinson’s disease. Striatal DAT imaging may be a useful indicator of apathy/anhedonia risk that could inform intervention strategies.