bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reelin haploinsufficiency affects skilled motor performance associated with suppression of training-induced gene enrichment, synaptic function and activity-dependent cortical plasticity in mice
Authors: Nishibe Mariko , Toyoda Hiroki , Katsuyama Yu 
Published: October 2020

AbstractRELN (Reelin) is one of the genes implicated in neurodevelopmental psychiatric vulnerability. Patients with neurodevelopmental disorders can experience impairments in fine motor skills. While Reelin modulates synaptic function, whether Reelin haploinsufficiency affects activity-dependent cortical plasticity which supports development of skilled movement is unclear. Here, heterozygousReelermutant (HRM) andDab1floxed/ +;Emx1-Cremice both displayed learning improvements measured by the reach-to-grasp task, but their performance levels of the forelimb motor skill were lower, compared with controls. The level of skilled motor performance was correlated with the area of cortical representations of the trained forelimb, examined after 10 days of training. Furthermore, we hypothesized that the genetic haploinsufficiency also alters changes that occur during the early phase of the training. Examined on day 3, the training induced synaptic modifications of the layer III cortical neurons in (wild-type) WT mice, which were contributed by synaptic potentiation and increase in spontaneous action-potential driven glutamatergic-transmission. On the other hand, the basal excitatory and inhibitory synaptic function were depressed, affected both by presynaptic and postsynaptic synaptic impairments in naive HRM; and thus, no further training-induced synaptic plasticity occurred in HRM. Lastly, examined after 3 days of training, the gene enrichment observed in trained WT mice was absent in trained HRM mice. The finding suggests the Reelin haploinsufficiency alters the skilled motor function; and we propose the suppression of gene enrichment, and synaptic abnormality led by the genetic insufficiency may contribute to impede the occurrence of activity-dependent cortical plasticity.Significance StatementImpairments in fine motor skills occur in subjects with neurodevelopmental disorders. We report a mutation relevant to the neurodevelopmental disorders can impact the cortical plasticity associated with skilled motor function. In wild-type mice, the motor training induced extensive activity-dependent cortical map plasticity, synaptic modifications through synaptic potentiation and excitatory-transmission increase, as well as enrichments in certain gene expressions. On the other hand, mice with Reelin haploinsufficiency (presumed mouse model of neurodevelopmental disorders) exhibited lower level of skilled motor performance, and the underlying correlates shown in wild-type mice were found suppressed. We conclude the suppression of gene enrichment, and synaptic abnormality due to Reelin haploinsufficiency may underlie the limited development of activity-dependent cortical plasticity, contributing to impairments in motor skills.
Spontaneous emergence of behaviorally relevant motifs in human motor cortex
Authors: Livne Tomer , Kim DoHyun , Metcalf Nicholas V. , Shulman Gordon L. , Corbetta Maurizio 
Published: October 2020

AbstractSpontaneous neural activity has been shown to preserve the inter-regional structure of cortical activity evoked by a task. It is unclear, however, whether patterns of spontaneous activity within a cortical region comprise representations associated with specific behaviors or mental states. The current study investigated the hypothesis that spontaneous neural activity in human motor cortex represents motor responses that commonly occur in daily life. To test this hypothesis 15 healthy participants were scanned in a 3T fMRI scanner while performing four simple hand movements differing by their daily life relevance, and while not performing any specific task (resting-state scans). Using the task data, we identified cortical patterns in a motor ROI corresponding to the different hand movements. These task-defined patterns were compared to spontaneous cortical activity patterns in the same motor ROI. The results indicated a higher similarity of the spontaneous patterns to the most common hand movement than to the least common hand movement. This finding provides the first evidence that spontaneous activity in human cortex forms fine-scale, patterned representations associated with behaviors that frequently occur in daily life.
Diversity of ACE2 and its interaction with SARS-CoV-2 receptor binding domain
Authors: Low-Gan Jessie , Huang Ruiqi , Warner Gabrielle , Kelley Abigail , McGregor Duncan , Smider Vaughn 
Published: October 2020

AbstractCOVID-19, the clinical syndrome caused by the SARS-CoV-2 virus, has rapidly spread globally causing tens of millions of infections and over a million deaths. The potential animal reservoirs for SARS-CoV-2 are currently unknown, however sequence analysis has provided plausible potential candidate species. SARS-CoV-2 binds to the angiotensin I converting enzyme 2 (ACE2) to enable its entry into host cells and establish infection. We analyzed the binding surface of ACE2 from several important animal species to begin to understand the parameters for the ACE2 recognition by the SARS-CoV-2 spike protein receptor binding domain (RBD). We employed Shannon entropy analysis to determine the variability of ACE2 across its sequence and particularly in its RBD interacting region, and assessed differences between various species’ ACE2 and human ACE2. As cattle are a known reservoir for coronaviruses with previous human zoonotic transfer, and has a relatively divergent ACE2 sequence, we compared the binding kinetics of bovine and human ACE2 to SARS-CoV-2 RBD. This revealed a nanomolar binding affinity for bovine ACE2 but an approximate ten-fold reduction of binding compared to human ACE2. Since cows have been experimentally infected by SARS-CoV-2, this lower affinity sets a threshold for sequences with lower homology to human ACE2 to be able to serve as a productive viral receptor for SARS-CoV-2.
Biotransformation of lindane (γ-hexachlorocyclohexane) to non-toxic end products by sequential treatment with three mixed anaerobic microbial cultures
Authors: Puentes Jácome Luz A. , Lomheim Line , Gaspard Sarra , Edwards Elizabeth A. 
Published: October 2020

AbstractThe γ isomer of hexachlorocyclohexane (HCH), also known as lindane, is a carcinogenic persistent organic pollutant. Lindane was used worldwide as an agricultural insecticide. Legacy soil and groundwater contamination with lindane and other HCH isomers is still a big concern. The biotic reductive dechlorination of HCH to non-desirable and toxic lower chlorinated compounds such as monochlorobenzene (MCB) and benzene, among others, has been broadly documented. Here, we demonstrate for the first time that complete biotransformation of lindane to non-toxic end products is attainable using a sequential treatment approach with three mixed anaerobic microbial cultures referred to as culture I, II, and III. Biaugmentation with culture I achieved dechlorination of lindane to MCB and benzene. Culture II was able to dechlorinate MCB to benzene, and finally, culture III carried out methanogenic benzene degradation. DistinctDehalobacterpopulations, corresponding to different 16S rRNA amplicon sequence variants in culture I and culture II, were responsible for lindane and MCB dechlorination, respectively. This study continues to highlight key roles ofDehalobacterspp. as chlorobenzene- and HCH-organohalide-respiring bacteria and demonstrates that sequential treatment with specialized anaerobic cultures may be explored at field sites in order to address legacy soil and groundwater contamination with HCH.
Assessment of ANG variants in Parkinson’s disease
Authors: Grenn Francis P. , Moore Anni , Bandres-Ciga Sara , Krohn Lynne , Blauwendraat Cornelis 
Published: October 2020

AbstractGenetic risk factors are occasionally shared between different neurodegenerative diseases. Previous studies have linked ANG, a gene encoding angiogenin, to both Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Functional studies suggest ANG plays a neuroprotective role in both PD and ALS by reducing cell death. We further explored the genetic association between ANG and PD by analyzing genotype data from the International Parkinson’s Disease Genomics Consortium (IPDGC) (14,671 cases and 17,667 controls) and whole genome sequencing (WGS) data from the Accelerating Medicines Partnership - Parkinson’s disease initiative (AMP-PD, https://amp-pd.org/) (1,647 cases and 1,050 controls). Our analysis did not replicate the findings of previous studies and found no significant association between ANG variants and PD risk.
Long-term monitoring of SARS-CoV-2 in wastewater of the Frankfurt metropolitan area in Southern Germany
Authors: Agrawal Shelesh , Orschler Laura , Lackner Susanne 
Published: October 2020

AbstractWastewater-based epidemiology (WBE) is a great approach that enables us to comprehensively monitor the community to determine the scale and dynamics of infections in a city, particularly in metropolitan cities with a high population density. Therefore, we monitored the time course of the SARS-CoV-2 RNA concentration in raw sewage in the Frankfurt metropolitan area, the European financial center. To determine the SARS-CoV-2 concentration in sewage, we continuously collected samples from two wastewater treatment plant (WWTP) influents (Niederrad and Sindlingen) serving the Frankfurt metropolitan area and performed RT-qPCR analysis targeting three genes (N gene, S gene, and ORF1ab gene). In August, a resurgence in the SARS-CoV-2 RNA load was observed, reaching 3 x 1013 copies/day, which represents similar levels compared to April with approx. 2 x 1014 copies/day. This corresponds to an also continuous increase again in COVID-19 cases in Frankfurt since August, with an average of 28.6 incidences, compared to 28.7 incidences in April. Different temporal dynamics were observed between different sampling points, indicating local dynamics in COVID-19 cases within the Frankfurt metropolitan area. The SARS-CoV-2 load to the WWTP Niederrad ranged from approx. 4 x 1011 to 1 x 1015 copies/day, the load to the WWTP Sindlingen from approx. 1 x 1011 to 2 x 1014 copies/day, which resulted in a preceding increase in these loading in July ahead of the weekly averaged incidences. The study shows that WBE has the potential as early warning system for SARS-CoV-2 infections and as monitoring system to identify global hotspots of COVID-19.
Neural adaptation of cingulate and insular activity during delayed fear extinction: A replicable pattern across assessment sites and repeated measurements
Authors: Ridderbusch Isabelle C. , Wroblewski Adrian , Yang Yunbo , Richter Jan , Hollandt Maike , Hamm Alfons O. , Wittchen Hans-Ulrich , Ströhle Andreas , Arolt Volker , Margraf Jürgen , Lueken Ulrike , Herrmann Martin J. , Kircher Tilo , Straube Benjamin 
Published: October 2020

AbstractAdapting threat-related memories towards changing environments is a fundamental ability of organisms. One central process of fear reduction is suggested to be extinction learning, experimentally modeled by extinction training that is repeated exposure to a previously conditioned stimulus (CS) without providing the expected negative consequence (unconditioned stimulus, US). Although extinction training is well investigated, evidence regarding process-related changes in neural activation over time is still missing. Using optimized delayed extinction training in a multicentric trial we tested whether: 1) extinction training elicited decreasing CS-specific neural activation and subjective ratings, 2) extinguished conditioned fear would return after presentation of the US (reinstatement), and 3) results are comparable across different assessment sites and repeated measures. We included 100 healthy subjects (measured twice, 13-week-interval) from six sites. 24h after fear acquisition training, extinction training, including a reinstatement test, was applied during fMRI. Alongside, participants had to rate subjective US-expectancy, arousal and valence. In the course of the extinction training, we found decreasing neural activation in the insula and cingulate cortex as well as decreasing US-expectancy, arousal and negative valence towards CS+. Re-exposure to the US after extinction training was associated with a temporary increase in neural activation in the anterior cingulate cortex (exploratory analysis) and changes in US-expectancy and arousal ratings. While ICCs-values were low, findings from small groups suggest highly consistent effects across time-points and sites. Therefore, this delayed extinction fMRI-paradigm provides a solid basis for the investigation of differences in neural fear-related mechanisms as a function of anxiety-pathology and exposure-based treatment.Clinical Trials RegistrationRegistry names: Deutsches Register Klinischer Studien (DRKS) – German Clinical Trails RegisterClinicalTrials.govRegistration ID-numbers: DRKS00008743DRKS00009687ClinicalTrials.gov Identifier: NCT02605668URLs: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00008743https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00009687https://clinicaltrials.gov/ct2/show/NCT02605668
Social inequalities in human mobility during the Spanish lockdown and post-lockdown in the Covid-19 pandemic of 2020
Authors: Hernando Alberto , Mateo David , barrios Ignacio , Plastino Angelo 
Published: October 2020

AbstractMany countries established strong population lockdowns as a response to the pandemic of COVID-19 in 2020. While these measures proved efficient in stopping the spreading of the virus, they also introduced collateral effects in the economies of these countries. We report in this work that the imprints in mobility of both the lockdown and post-lockdown on the Spanish population are measurable by means of the daily radius of gyration using mobile phone data. We cross mobility with economic data segmented by average salary per person so as to find large inequalities between low- and high-income populations. Indeed, low-income populations typically show a 17% higher radius of gyration than high-income ones during pre-lockdown (8.1 km vs. 6.9 km). However, this relative difference grows to a maximum during lock-down (3.3 km vs. 900 m) since most of the essential workers (carriers, nurses, supermarket cashiers, farmworkers, etc.) belong to the first segment. Post-lockdown shows reversed inequality in the weeks during summer vacations as high-income populations multiplied their pre-lockdown radius by 70% as a rebound effect driven by leisure, while low-income populations recovered their normal pre-lockdown radius. This period is correlated with an extraordinary increase in the number of new Covid cases, which stabilized after the holyday weeks once at the so-called new normal. We find that this new normal emphasizes the pre-lockdown inequalities in mobility between low- and high-income population, increasing the inequality up to a 47%. These results show the relevance of devising measures that could account for potential collateral inequalities.
Modelling the impact of COVID-19-related programme interruptions on visceral leishmaniasis in India
Authors: Le Rutte Epke A , Coffeng Luc E , Muñoz Johanna , de Vlas Sake J 
Published: October 2020

AbstractBackgroundIn March 2020, India declared a nationwide lockdown to control the spread of COVID-19. As a result, control efforts against visceral leishmaniasis (VL) were interrupted.MethodsUsing an established age-structured deterministic VL transmission model, we predicted the impact of a 6 to 24-month programme interruption on the timeline towards achieving the VL elimination target, as well as on the increase of VL cases. We also explored the potential impact of a mitigation strategy after the interruption.ResultsDelays towards the elimination target are estimated to range between 0 to 9 years. Highly endemic settings where control efforts have been ongoing for 5-8 years are most affected by an interruption, for which we identified a mitigation strategy to be most relevant. However, more importantly, all settings can expect an increase in the number of VL cases. This increase is substantial even for settings with a limited expected delay in achieving the elimination target.ConclusionBesides implementing mitigation strategies, it is of great importance to try and keep the duration of the interruption as short as possible, to prevent new individuals from becoming infected with VL, and continue the efforts towards VL elimination as a public health problem in India.
Risk Factors for Mild, Moderate, and Severe Alcohol Use Disorder (AUD) in a sample of adult substance users: Implications for DSM-5 AUD Classification
Authors: Mannes Zachary L. , Shmulewitz Dvora , Livne Ofir , Stohl Malka , Hasin Deborah 
Published: October 2020

AbstractThough risk factors of Alcohol Use Disorder (AUD) have been well-studied, information is lacking on whether clinical characteristics differentiate between the three levels of severity (mild, moderate, severe) that were established for the first time in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). Therefore, in this study, we examined the association between alcohol consumption, mental and physical health, and functional impairment with the three DSM-5 AUD severity levels among adults age 18+ (N=588) pre-screened for problems with at least one substance. Participants recruited between 2016-2019 completed measures of AUD, harmful alcohol use, psychiatric conditions, and mental, physical, and social functional impairment. For each predictor, a multinomial logistic regression model was used to evaluate the association with a four-level AUD outcome (mild, moderate, severe, vs none), controlling for sociodemographic characteristics and other substance use. Twelve-month prevalence of none, mild, moderate, and severe DSM-5 AUD was 34.0%, 12.2%, 13.4%, and 40.3%, respectively. Participants reported a mean of 11.3 (SD=9.90) days of alcohol use in the past month, nearly half (48.0%) perceived to have a major problem with alcohol, and 61.4% met the threshold for harmful drinking. Multinomial logistic regression demonstrated that compared to the reference group (no AUD), all three AUD severity levels were associated with drinking frequency, problematic, and harmful alcohol use. However, only severe AUD was associated with personality disorders: (AOR=1.91, 95% CI=1.28, 2.86), MDD (AOR= 2.44, 95% CI= 1.62, 3.66) or PTSD (AOR= 1.65, 95% CI= 1.00, 2.71),. Similarly, only severe AUD was associated with impaired physical (AOR= 1.63, 95% CI= 1.01, 2.61), mental (AOR= 1.80, 95% CI= 1.16, 2.79), and social functioning (AOR= 1.87, 95% CI= 1.39, 2.51). This study adds to existing literature on clinical correlates of AUD by further elucidating the risk factors of the different AUD severity groups, while also highlighting an important, differential observation wherein measures of psychiatric disorders and functional impairment were only associated with severe AUD. The study suggests that the DSM-5 category of severe AUD most closely corresponds to AUD cases often found in secondary or tertiary treatment settings, and that cases of mild or moderate AUD may warrant less intensive treatment approaches. Future investigations should seek to examine the validity of the DSM-5 AUD three-level severity distinction by using longitudinal designs to evaluate change in mental health and functioning over time, along with their association with AUD severity classification.
Phenome-wide HLA association landscape of 235,000 Finnish biobank participants
Authors: Ritari Jarmo , Koskela Satu , Hyvärinen Kati , FinnGen  , Partanen Jukka 
Published: October 2020

AbstractThe human leukocyte antigen (HLA) system is the single most important genetic susceptibility factor for many autoimmune diseases and immunological traits. However, in a range of clinical phenotypes the impact of HLA alleles or their combinations on the disease risk are not comprehensively understood.For systematic population-level analysis of HLA-phenotype associations we imputed the alleles of classical HLA genes in a discovery cohort of 146,630 and replication cohort of 89,340 Finns of whom SNP genotype data and 3,355 disease phenotypes were available as part of the FinnGen project.The results suggest HLA associations in phenotypes not reported previously and highlight interactions between HLA genes and alleles in autoimmune diseases. Furthermore, shared HLA alleles in autoimmune and infectious diseases support a genetic link between these diseases.
Prognostic value of early leukocyte fluctuations for recovery from traumatic spinal cord injury
Authors: Jogia T , Lübstorf T , Jacobson E , Scriven E , Atresh S , Liebscher T , Schwab JM , Kopp MA , Walsham J , Campbell KE , Ruitenberg MJ 
Published: October 2020

ABSTRACTBackgroundAcute traumatic spinal cord injury (SCI) induces a systemic immune response involving circulating white blood cells (WBC). How this response is influenced by overall trauma severity, the neurological level of injury and/or correlates with patient outcomes is poorly understood. The objective of this study was to identify relationships between early changes in circulating WBCs, injury characteristics, and long-term patient outcomes in individuals with traumatic SCI.MethodsWe retrospectively analysed data from n=161 SCI patients admitted to Brisbane’s Princess Alexandra Hospital (exploration cohort). Logistic regression models in conjunction with receiver-operator characteristic (ROC) analyses were used to assess the strength of specific links between the WBC response, respiratory infection incidence and neurological outcomes (American Spinal Injury Association Impairment Scale (AIS) grade conversion). An independent validation cohort from the Trauma Hospital Berlin, Germany (n=49) was then probed to assess the robustness of effects and to disentangle centre effects.ResultsWe find that the extent of acute neutrophilia in human SCI patients is positively correlated with New Injury Severity Scores (NISS) but inversely with the neurological outcome (AIS grade). Multivariate analysis demonstrated that acute SCI-induced neutrophilia is an independent predictor of AIS grade conversion failure, with an odds ratio (OR) of 4.16 and ROC area under curve (AUC) of 0.82 (p<0.0001). SCI-induced lymphopenia was separately identified as an independent predictor of better recovery (OR = 24.15; ROC AUC = 0.85, p<0.0001). Acute neutrophilia and increased neutrophil-lymphocyte ratios were otherwise significantly associated with respiratory infection presentation in both patient cohorts.ConclusionsOur findings demonstrate the prognostic value of modelling early circulating neutrophil and lymphocyte counts with patient characteristics for predicting the longer-term recovery after SCI.