bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hand preference and the corpus callosum: Is there really no association?
Authors: Raaf Nora , Westerhausen René 
Published: November 2022

AbstractOriginating from a series of morphometric studies conducted in the 1980s, it appears a widely held belief in cognitive neuroscience that the corpus callosum is larger in non-right handers than in right handers (RH). However, a recent meta-analysis challenges this belief by not finding significant differences in corpus callosum size between handedness groups. Yet, relying on the available published data, the meta-analysis was not able to account for a series of factors potential influencing its outcome, such as confounding effects of brain size differences and a restricted spatial resolution of previous callosal segmentation strategies. To address these remaining questions, we here analysed the midsagittal corpus callosum of N = 1057 participants from the Human Connectome Project (HCP 1200 Young Adults) to compare handedness groups based on consistency (e.g., consistent RH vs. mixed handers, MH) and direction of hand preference (e.g., RH vs. left handers). A possible relevance of brain-size differences was addressed by analysing callosal variability by both using forebrain volume (FBV) as covariate and utilising relative area (callosal area/thickness divided by FBV) as dependent variable. Callosal thickness was analysed at 100 measuring points along the structure to achieve high spatial resolution to detect subregional effects. However, neither of the conducted analyses was able to find significant handedness-related differences in callosal and the respective effect-sizes estimates were small. For example, comparing MH and consistent RH, the effect sizes for difference in callosal area were below a Cohen’sd= 0.1 (irrespective of how FBV was included), and narrow confidence intervals allowed to exclude effects above |d| = 0.2. Analysing thickness, effect sizes were belowd= 0.2 with confidence intervals not extending above |d| = 0.3. In this, the possible range of population effect sizes of hand preference on callosal morphology appears well below the effects commonly reported for factors like age, sex, or brain size. Effects on cognition or behaviour accordingly can be considered small, questioning the common practise to attribute performance differences between handedness groups to differences in callosal architecture.
Incorporating Pre-training Paradigm for Antibody Sequence-Structure Co-design
Authors: Gao Kaiyuan , Wu Lijun , Zhu Jinhua , Peng Tianbo , Xia Yingce , He Liang , Xie Shufang , Qin Tao , Liu Haiguang , He Kun , Liu Tie-Yan 
Published: November 2022

AbstractAntibodies are versatile proteins that can bind to pathogens and provide effective protection for human body. Recently, deep learning-based computational antibody design has attracted popular attention since it automatically mines the antibody patterns from data that could be complementary to human experiences. However, the computational methods heavily rely on the high-quality antibody structure data, which is quite limited. Besides, the complementarity-determining region (CDR), which is the key component of an antibody that determines the specificity and binding affinity, is highly variable and hard to predict. Therefore, data limitation issue further raises the difficulty of CDR generation for antibodies. Fortunately, there exists a large amount of sequence data of antibodies that can help model the CDR and alleviate the reliance on structured data. By witnessing the success of pre-training models for protein modeling, in this paper, we develop an antibody pre-trained language model and incorporate it into the (antigen-specific) antibody design model in a systemic way. Specifically, we first pre-train an antibody language model based on the sequence data, then propose a one-shot way for sequence and structure generation of CDR to avoid the heavy cost and error propagation from an autoregressive manner, and finally leverage the pre-trained antibody model for the antigen-specific antibody generation model with some carefully designed modules. Through various experiments, we show that our method achieves superior performance over previous baselines on different tasks, such as sequence and structure generation, antigen-binding CDR-H3 design.
Characterisation of fasting and postprandial NMR metabolites: insights from the ZOE PREDICT 1 Study
Authors: Bermingham Kate M , Mazidi Mohsen , Franks Paul W , Maher Tyler , Valdes Ana M , Linenberg Inbar , Wolf Jonathan , Hadjigeorgiou George , Spector Tim D , Menni Cristina , Ordovas Jose M , Berry Sarah E , Hall Wendy L 
Published: November 2022

AbstractBackgroundPostprandial metabolomic profiles and their inter-individual variability are not well characterised. Here we describe postprandial metabolite changes, their correlations with fasting values and their inter- and intra-individual variability following a standardised meal in the ZOE PREDICT 1 cohort.MethodsIn the ZOE PREDICT 1 study (n= 1,002 (NCT03479866)), 250 metabolites, mainly lipids, were measured by Nightingale NMR panel in fasting and postprandial (4 and 6 h after a 3.7 MJ mixed nutrient meal, with a second 2.2 MJ mixed nutrient meal at 4 h) serum samples. For each metabolite, inter- and intra-individual variability over-time was evaluated using linear mixed modelling and intraclass-correlation coefficients (ICC) calculated.ResultsPostprandially, 85% (of 250 metabolites) significantly changed from fasting at 6h (47% increased, 53% decreased; Kruskal-Wallis), with 37 measures increasing by >25%, and 14 increasing by >50%. The largest changes were observed in very large lipoprotein particles and ketone bodies. Seventy-one percent of circulating metabolites were strongly correlated (Spearman’s rho >0.80) between fasting and postprandial timepoints, and 5% were weakly correlated (rho <0.50). The median ICC of the 250 metabolites was 0.91 (range 0.08-0.99). The lowest ICCs (ICC<0.40, 4% of measures) were found for glucose, pyruvate, ketone bodies (β-hydroxybutyrate, acetoacetate, acetate) and lactate.ConclusionsIn this large-scale postprandial metabolomic study, circulating metabolites were highly variable between individuals following a mixed challenge meal. Findings suggest that a meal challenge may yield postprandial responses divergent from fasting measures, specifically for glycolysis, essential amino acid, ketone body and lipoprotein size metabolites.
Reproducible switching between a walled and cell wall-deficient lifestyle of actinomycetes using gradient agar plates
Authors: Lubbers Maarten , van Wezel Gilles P. , Claessen Dennis 
Published: November 2022

ABSTRACTThe cell wall is a shape-defining structure that envelopes almost all bacteria, protecting them from biotic and abiotic stresses. Paradoxically, some filamentous actinomycetes have a natural ability to shed their cell wall under influence of hyperosmotic stress. These wall-deficient cells can revert to their walled state when transferred to a medium without osmoprotection but often lyse due to their fragile nature. Here, we designed plates with an osmolyte gradient to reduce cell lysis and thereby facilitating the transition between a walled and wall-deficient state. These gradient plates allow determining of the osmolyte concentration where switching takes place, thereby enabling careful and reproducible comparison between mutants affected by switching. Exploring these transitions could give valuable insights into the ecology of actinomycetes and their biotechnological applications.HIGHLIGHTS-Using agar plates with a gradient of osmoprotectants, revertant Streptomycetes can gradually revert to a walled state, thereby dramatically decreasing lysis.-Our method allows precise determination of the osmolyte concentration where reversion takes place, allowing careful and reproducible comparison between mutants.-Gradient agar plates can also be used to study chemical differentiation in Streptomycetes as a response to osmotic stress.
Inhibition of proline tyrosine kinase 2 (Pyk2) phosphorylation during adherent-invasiveEscherichia coliinfection inhibits intra-macrophage replication and inflammatory cytokine release
Authors: Li Xiang , Ormsby Michael J. , Fallata Ghaith , Meikle Lynsey M. , Xu Damo , Wall Daniel M. 
Published: November 2022

AbstractAdherent-invasiveEscherichia coli(AIEC) have been implicated in the aetiology of Crohn’s Disease (CD). They are characterized by an ability to adhere to and invade intestinal epithelial cells, and to replicate intracellularly in macrophages resulting in inflammation. Proline-rich tyrosine kinase 2 (PYK2) has previously been identified as a risk locus for inflammatory bowel disease through genome wide association studies. It is overexpressed in patients with colorectal cancer, a major long-term complication of CD. Here we show that Pyk2 levels are significantly increased during AIEC infection of murine macrophages while an inhibitor of Pyk2, PF-431396 hydrate, significantly decreased intramacrophage AIEC numbers. Imaging flow cytometry indicated that Pyk2 inhibition blocked intramacrophage replication of AIEC with no change in the overall number of infected cells, but a significant reduction in bacterial burden per cell. This reduction in intracellular bacteria resulted in a 20-fold decrease in tumour necrosis factor α secretion by cells post-AIEC infection. These data demonstrate a key role for Pyk2 in modulating AIEC intracellular replication and associated inflammation and may provide a new avenue for future therapeutic intervention in CD.
Efficient mechano-enzymatic hydrolysis of polylactic acid under moist-solid conditions
Authors: Pérez-Venegas Mario , Friščić Tomislav , Auclair Karine 
Published: November 2022

ABSTRACTQuantitative mechano-enzymatic depolymerisation of polylactic acid to lactic acid was achieved at 55°C using theHumicola insolenscutinase enzyme in moist-solid reaction mixtures. The resulting lactic acid was easily recovered, and the crude product was pure enough to be used in further synthesis of a value-added compound, a known benzimidazole-based drug precursor. The presented mechano-enzymatic depolymerisation strategy enables the closed-loop recycling of untreated polylactic acid under mild conditions, using a renewable, non-toxic catalyst and producing minimum solvent waste.
The global groundwater resistome: core antibiotic resistance genes, their dynamics and drivers
Authors: Kampouris Ioannis D. , Bengtsson-Palme Johan , Babin Doreen , Gallego Sara , Li Bing , Smalla Kornelia , Berendonk Thomas U. , Klümper Uli 
Published: November 2022

AbstractDespite the importance of groundwater as a drinking water resource, currently, no comprehensive picture regarding the global levels of antibiotic resistance genes (ARGs) in groundwater environments exists. Moreover, the biotic and abiotic factors that shape the groundwater resistome on the global scale remain to be explored. Herein, we attempted to fill this knowledge gap throughin silicore-analysis of publicly available global groundwater metagenomes. First, nine ARGs encoding resistance to aminoglycosides (aadA,aph(3’), andant(3’’)), sulfonamides (sul1 andsul2), β-lactams (blaOXAandblaTEM), tetracyclines (tet(C)) and macrolides (msr(E)) were identified to constitute the core groundwater resistome with high detection and abundance levels. Second, the global drivers of groundwater resistome composition were identified by applying a structural equation model with mixed effects to disentangle the individual contributions of each abiotic and biotic factor. Most notably, global effects of the origin of groundwater samples on the resistome were detected with samples from high-income countries (HICs) constantly displaying lower ARG and mobile genetic element (MGE) abundances than those from low-and-middle-income countries (LMICs). While these effects were consistent across antibiotic classes, biotic factors such as interactions of the groundwater microbiome with fungal or bacterial natural producers of antibiotics, or the co-occurrence of ARGs on mobile genetic elements (MGEs) played significant roles in shaping abundance patterns of resistance towards individual antibiotic classes. Only few ARGs correlated to individual bacterial genera, with microbial community composition in general weakly associated with resistome composition. In conclusion, we provide a first global picture of the resistome of low-anthropogenic impacted groundwater environments and the underlying anthropogenic and biotic drivers shaping it, which can be used as a baseline in future surveillance of antibiotic resistance.
Species-conserved mechanisms of abstract rule learning promote cognitive flexibility in complex environments
Authors: Bähner Florian , Popov Tzvetan , Boehme Nico , Hermann Selina , Merten Tom , Zingone Hélène , Koppe Georgia , Meyer-Lindenberg Andreas , Toutounji Hazem , Durstewitz Daniel 
Published: November 2022

SummaryRapid learning in complex and changing environments is a hallmark of intelligent behavior. Humans achieve this in part through abstract concepts applicable to multiple, related situations. It is unclear, however, whether some of the underlying computational mechanisms also exist in other species. We combined behavioral, computational and electrophysiological analyses of a multidimensional rule-learning paradigm in rats and humans. We report that both species infer task rules by sequentially testing different hypotheses, rather than learning the correct action for all possible combinations of task-related cues. Neural substrates of hypothetical rules were detected in prefrontal network activity of both species. This species-conserved mechanism reduces task dimensionality and explains key experimental observations: sudden behavioral transitions and facilitated learning after prior experience. Our findings open the black box of hypothesis testing in rodents and provide a foundation for the translational investigation of impaired cognitive flexibility.
Chronic Alcohol Drinking Drives Sex-Specific Differences in Affective Behavior and Medial Prefrontal Cortex Activity in CRF1:Cre:Tdtomato Transgenic Rats
Authors: Quadir SG , Arleth GM , Cone MG , High MW , Ramage MC , Effinger DP , Echeveste-Sanchez M , Herman MA 
Published: November 2022

ABSTRACTAlcohol use disorders (AUDs) are characterized by compulsive alcohol use, loss of control over intake, and a negative emotional state during abstinence. While AUDs are associated with both mood and chronic pain disorders, the relationship between these associations remains unclear. Corticotropin releasing factor-1 receptor (CRF1) has been implicated in alcohol (EtOH) use, affective states, and pain sensitivity; often in a sex-dependent manner. Using CRF1-cre transgenic rats, we found no sex differences in basal affective behavior with the exception of mechanical sensitivity, where females were more sensitive to mechanical stimuli. Following baseline testing, rats began EtOH (or water) drinking under intermittent access conditions. Females consumed more alcohol in the first week, but overall EtOH intake was not significantly different between males and females. Following 3-4 weeks of drinking, rats were tested again for negative affect. EtOH drinking decreased mechanical sensitivity, but no other group effects were observed. However, individual EtOH intake was directly correlated with anxiety- and depressive-like behavior in both sexes. Interestingly, EtOH intake inversely correlated with thermal sensitivity in males only. There were no group differences in CRF1+ neuronal activity in either prelimbic or infralimbic cortices, but final session EtOH intake was significantly correlated with activity in CRF1+ neurons in the infralimbic cortex. Together, our results suggest complex interplay between affective state, EtOH drinking, and the role of prefrontal cortex CRF1-containing neurons in mediating these behaviors. Additionally, these results highlight the importance of examining individual differences in AUD-related behaviors.SIGNIFICANCE STATEMENTDespite alcohol use disorders being extremely comorbid with mood and pain disorders, there is still a limited understanding of the interaction and directionality between the them. To investigate this problem, rats were tested for affective behavior before and after being allowed to drink alcohol for 6 weeks. While baseline behavior did not predict subsequent intake, alcohol intake predicted both anxiety- and depressive-like behavior. These findings were accompanied by increased activity of the corticotropin releasing factor 1 containing neurons in the infralimbic region of the prefrontal cortex. Together, these findings reveal a new mechanism for understanding alcohol use.
Membrane Voltage Dynamics of Parvalbumin Interneurons Orchestrate Hippocampal Theta Rhythmicity
Authors: Tseng Hua-an , Mount Rebecca A. , Lowet Eric , Gritton Howard J. , Cheung Cyrus , Han Xue 
Published: November 2022

AbstractHippocampal network activity at theta frequencies (5-10Hz) is important for behavior. However, it remains unclear how behaviorally-relevant network theta rhythms arise and interact with cellular dynamics to dictate spike timing. We performed membrane voltage (Vm) imaging of individual CA1 pyramidal cells and parvalbumin interneurons with simultaneous local field potential (LFP) recordings in mice during locomotion. We found that Vm theta rhythms organize spike timing in both cell types regardless of behavioral conditions, but the Vm of parvalbumin interneurons is better synchronized with LFP. The temporal relationships between spikes and LFP theta reliably reflect the Vm-LFP relationships in parvalbumin cells, but not in pyramidal cells. Thus, cellular theta rhythms broadly organize spike timing in CA1 neurons, and parvalbumin interneurons are critical in coordinating network theta rhythms.One-Sentence SummaryCellular membrane voltage of parvalbumin interneurons organizes spiking and network dynamics in the hippocampus.
The GLM-Spectrum: A multilevel framework for spectrum analysis with covariate and confound modelling
Authors: Quinn Andrew J , Atkinson Lauren Z , Gohil Chetan , Kohl Oliver , Pitt Jemma , Zich Catharina , Nobre Anna C , Woolrich Mark W 
Published: November 2022

AbstractThe frequency spectrum is a central method for representing the dynamics within electrophysiological data. Some widely used spectrum estimators make use of averaging across time segments to reduce noise in the final spectrum. The core of this approach has not changed substantially since the 1960s, though many advances in the field of regression modelling and statistics have been made during this time. Here, we propose a new approach, the General Linear Model (GLM) Spectrum, which reframes time averaged spectral estimation as multiple regression. This brings several benefits, including the ability to do confound modelling, hierarchical modelling and significance testing via non-parametric statistics.We apply the approach to a dataset of EEG recordings of participants who alternate between eyes-open and eyes-closed resting state. The GLM-Spectrum can model both conditions, quantify their differences, and perform denoising through confound regression in a single step. This application is scaled up from a single channel to a whole head recording and, finally, applied to quantify age differences across a large group-level dataset. We show that the GLM-Spectrum lends itself to rigorous modelling of within- and between-subject contrasts as well as their interactions, and that the use of model-projected spectra provides an intuitive visualisation. The GLM-Spectrum is a flexible framework for robust multi-level analysis of power spectra, with adaptive covariance and confound modelling.
Distributed Compact Plasma Reactor Sterilization for Planetary Protection in Space Missions
Authors: Choudhury Bhaswati , Revazishvili Tamara , Lozada Maria , Roy Sarthak , Mastro Emma Noelle , Portugal Sherlie , Roy Subrata 
Published: November 2022

AbstractThis paper presents a proof-of-concept study establishing effectiveness of the Active Plasma Sterilizer (APS) for sterilization in planetary protection. The APS uses Compact Portable Plasma Reactors (CPPRs) to produce surface dielectric barrier discharge, a type of cold plasma, using ambient air to generate and distribute reactive species like ozone used for decontamination. Sterilization tests were performed with pathogenic bacteria (Escherichia coli and Bacillus subtilis) on materials (Aluminum, Polycarbonate, Kevlar and Orthofabric) relevant to space missions. Results show that the APS can achieve 4 to 5 log reductions of pathogenic bacteria on four selected materials, simultaneously at 11 points within 30 minutes, using power of 13.2 ± 2.22 W. Spatial sterilization data shows the APS can uniformly sterilize several areas of a contaminated surface within 30 minutes. Ozone penetration through Kevlar and Orthofabric layers was achieved using the CPPR with no external agent assisting penetration. Preliminary material compatibility tests with SEM analysis of the APS exposed materials showed no significant material damage. Thus, this study shows the potential of the APS as a light-weight sustainable sterilization technology for planetary protection with advantages of uniform spatial decontamination, low processing temperatures, low exposure times, material compatibility and the ability to disinfect porous surfaces.
Sustained Modulation of Deep Brain Circuits with Focused Ultrasonic Waves
Authors: Webb Taylor D. , Wilson Matthew G. , Odeen Henrik , Kubanek Jan 
Published: November 2022

AbstractTranscranial focused ultrasound has the potential to noninvasively and systematically modulate deep brain circuits and impart sustained, neuroplastic effects in awake subjects. The intersection of these properties is critical for effective treatments of brain disorders, yet remains to be shown. Harnessing the full potential of transcranial ultrasound, we delivered 30-second stimuli into deep brain targets (left/right lateral geniculate nucleus) of non-human primates while they performed a visual discrimination task. This brief stimulation induced sustained and target-specific behavioral preference that persisted up to 15 minutes following the ultrasound offset. The polarity of the behavioral and neural effects suggested that ultrasound excited the stimulated circuits. The ultrasound was delivered into the deep brain daily for a period of more than 6 months, which enabled us to evaluate the safety of longterm stimulation. There were no detrimental effects on the animals’ discrimination accuracy over the course of this stimulation regimen. This study demonstrates ultrasound’s capacity to condition deep brain circuits in a safe and treatment-relevant manner in awake subjects, and provides a basis for effective and safe translations into humans.HighlightsTranscranial ultrasound induces effective and sustained modulation of deep brain circuits.The deep brain modulation biases choice behavior of non-human primates.The deep brain modulation produces sustained elevation of high gamma activity.The stimulation, applied daily for several months, is safe.