bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mushroom body input connections form independently of sensory activity in Drosophila melanogaster
Authors: Hayashi Tatsuya , MacKenzie Alexander John , Ganguly Ishani , Smihula Hayley Marie , Jacob Miles Solomon , Litwin-Kumar Ashok , Caron Sophie Jeanne Cécile 
Published: November 2021

SUMMARYAssociative brain centers, such as the insect mushroom body, need to represent sensory information in an efficient manner. In Drosophila melanogaster, the Kenyon cells of the mushroom body integrate inputs from a random set of olfactory projection neurons, but some projection neurons — namely those activated by a few ethologically meaningful odors — connect to Kenyon cells more frequently than others. This biased and random connectivity pattern is conceivably advantageous, as it enables the mushroom body to represent a large number of odors as unique activity patterns while prioritizing the representation of a few specific odors. How this connectivity pattern is established remains largely unknown. Here, we test whether the mechanisms patterning the connections between Kenyon cells and projection neurons depend on sensory activity or whether they are hardwired. We mapped a large number of mushroom body input connections in anosmic flies — flies lacking the obligate odorant co-receptor Orco — and in wildtype flies. Statistical analyses of these datasets reveal that the random and biased connectivity pattern observed between Kenyon cells and projection neurons forms normally in the absence of most olfactory sensory activity. This finding supports the idea that even comparatively subtle, population-level patterns of neuronal connectivity can be encoded by fixed genetic programs and are likely to be the result of evolved prioritization of ecologically and ethologically salient stimuli.
Beyond Fixation: detailed characterization of neural selectivity in free-viewing primates
Authors: Yates Jacob L. , Coop Shanna H. , Sarch Gabriel H. , Wu Ruei-Jr , Butts Daniel A. , Rucci Michele , Mitchell Jude F. 
Published: November 2021

Virtually all vision studies use a fixation point to stabilize gaze, rendering stimuli on video screens fixed to retinal coordinates. This approach requires trained subjects, is limited by the accuracy of fixational eye movements, and ignores the role of eye movements in shaping visual input. To overcome these limitations, we developed a suite of hardware and software tools to study vision during natural behavior in untrained subjects. We show this approach recovers receptive fields and tuning properties of visual neurons from multiple cortical areas of marmoset monkeys. Combined with high-precision eye-tracking, it achieves sufficient resolution to recover the receptive fields of foveal V1 neurons. These findings demonstrate the power of free viewing to characterize neural response while simultaneously studying the dynamics of natural behavior.HighlightsWe introduce a free-viewing paradigm for studying neural mechanisms of visual processing during active visionReceptive fields (RFs) and neural selectivity in primary visual cortex (V1) and area MT can be extracted during free-viewing in minimally-trained subjectsNovel high-resolution eye tracking in this context supports detailed measurements of receptive fields in foveal V1
Predictions of arrhythmic, heart failure and mortality outcomes in pericarditis using automatic electrocardiogram analysis
Authors: Lakhani Ishan , Zhou Jiandong , Wong Michelle Vangi , Lee Sharen , Lau Jovy Ka Yiu , Shi Silverdew , Wong Wing Tak , Liu Tong , Zhang Qingpeng , Tse Gary 
Published: November 2021

AbstractBackgroundPericarditis is a relatively rare disease with a global burden. Despite its strong association with adverse cardiovascular outcomes, identification of patients at risk of future heart failure or arrhythmic events is difficult. In the following study, automated electrocardiogram (ECG) were used to predict new onset ventricular tachycardia/fibrillation (VT/VF), atrial fibrillation (AF) and heart failure with reduced ejection fraction (HF) in an Asian cohort of pericarditis patients.MethodsConsecutive patients admitted to a single tertiary center in Hong Kong, China, for a diagnosis of pericarditis between 1st January 2005 and 31st December 2019 with baseline ECG measurements were included. Patients with existing AF or HF were excluded. The follow-up period was until the 31st December 2020, or death. Cox regression was applied to identify significant predictors of the primary outcomes (incident VT/VF, AF or HF).ResultsA total of 874 patients were included. The cohort was 57% male and had a median age of 59 (IQR: 50-70) years old. During follow-up, 57 patients (6.5%), 156 (17.8%) and 168 (19.2%) suffered from VT/VF, AF and HF, respectively. Cox regression identified baseline VT/VF, terminal angle of the QRS vector in the transverse plane, mean QRS duration and mean QTc intervals as significant predictors of incident VT/VF events, with only the former most maintaining significance in multivariate analysis. In contrast, baseline age, prior diagnoses of hypertension, initial angle and magnitude of the QRS vector in the transverse plane, P-wave and QRS axis in the frontal plane, ST segment axis in the frontal and horizontal planes, mean PT interval, mean PR segment duration and QTc intervals were all univariate predictors of incident AF, albeit only baseline age and initial angel of the QRS vector in the transverse plane retained significance after multivariate adjustment. As it pertains to new-onset HF, several clinical and electrocardiographic parameters demonstrated an association with HF in univariate analysis, with prior diagnosis of HT or DM, initial QRS angle in transverse plane, I 40 in horizontal axis, ST-segment axis in the horizontal plane, T-wave frontal axis and atrial rate, of which, except for prior diagnosis of DM, I40 in horizontal axis and T-wave frontal axis, all variables showcased significant relationships in multivariate analysisInterpretationAF and HF are relatively common complications VT/VF occurs less frequently in the context of pericarditis. Different clinical and ECG predictors of these outcomes were identified. Future studies are still needed to evaluate their use for risk stratification in the clinical setting.
The Recombination Landscape of the Khoe-San - the Upper Limits of Recombination Divergence in Humans
Authors: van Eeden Gerald , Uren Caitlin , Pless Evlyn , Mastoras Mira , van der Spuy Gian D. , Tromp Gerard , Henn Brenna M. , Möller Marlo 
Published: November 2021

AbstractRecombination maps are important resources for epidemiological and evolutionary analyses, however, there are currently no recombination maps representing any African population outside of those with West African ancestry. We inferred the demographic history for the Nama, an indigenous Khoe-San population of southern Africa, and derived a novel, population-specific recombination map from the whole genome sequencing of 54 Nama individuals. We hypothesized that there are no publicly available recombination maps representative of the Nama, considering the deep population divergence and subsequent isolation of the Khoe-San from other African groups. We showed that the recombination landscape of the Nama does not cluster with any continental groups with publicly available representative recombination maps. Finally, we used selection scans as an example of how fine-scale differences between the Nama recombination map and the combined Phase II HapMap recombination map can impact the outcome of selection scans.
Mesowestern Blot: Simultaneous Analysis of Hundreds of Sub-Microliter Lysates
Authors: Zadeh Cameron O. , Huggins Jonah R. , Westbury Baylee C. , Interiano William R. , Phillips S. Ashley , Erdem Cemal , Sarmah Deepraj , Dodd William B. , Meredith Wesley O. , Birtwistle Marc R. 
Published: November 2021

AbstractWestern blotting is a widely-used technique for molecular-weight-resolved analysis of proteins and their post-translational modifications, but has been refractory to affordable scale-up. Here, we report the Mesowestern blot, which uses a 3D-printable gel-casting mold to enable affordable, high-throughput Western blotting with standard sample preparation and small (<1 uL) sample sizes. The casted polyacrylamide gel contains 336, 0.5 uL micropipette-loadable sample wells arranged within a standard microplate footprint. Polyacrylamide % can be altered to change molecular weight resolution range. Proof-of-concept experiments using both infrared-fluorescent molecular weight protein ladder as well as cell lysate (RIPA buffer) demonstrate protein loaded in Mesowestern gels is amenable to the standard Western blotting steps. The main difference between Mesowestern and traditional Western is that semi-dry horizontal instead of immersed vertical gel electrophoresis is used. The linear range of detection is approximately 2 orders of magnitude, with a limit of detection (for β-actin) of around 30 ng of total protein from mammalian cell lysates (~30-3000 cells). Because the gel mold is 3D-printable, users have significant design freedom for custom layouts, and there are few barriers to adoption by the typical cell and molecular biology laboratory already performing Western blots.
Intrinsically disordered regions of Tristetraprolin and DCP2 directly interact to mediate decay of ARE-mRNA
Authors: Maciej Vincent D. , Mateva Nevena , Dittmers Theresa , Chakrabarti Sutapa 
Published: November 2021

AbstractThe RNA binding protein Tristetraprolin (TTP) is a potent activator of mRNA decay, specifically for transcripts bearing AU-rich elements (AREs) in their 3′-untranslated regions. TTP functions as a mediator for mRNA decay by interacting with the decay machinery and recruiting it to the target ARE-mRNA. In this study, we report a weak, but direct interaction between TTP and the human decapping enzyme DCP2, which impacts the stability of ARE-transcripts. The TTP-DCP2 interaction is unusual as it involves intrinsically disordered regions (IDRs) of both binding partners. We show that the IDR of DCP2 has a propensity for oligomerization and liquid-liquid phase separation (LLPS)in vitro. Binding of TTP to DCP2 leads to its partitioning into phase-separated droplets formed by DCP2, suggesting that molecular crowding might facilitate the weak interaction between the two proteins and enable assembly of a decapping-competent mRNA-protein complex on TTP-bound transcripts in cells. Our studies underline the role of weak interactions in the cellular interaction network and their contribution towards cellular functionality.
Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2
Authors: Kosillo Polina , Ahmed Kamran M. , Roberts Bradley M. , Cragg Stephanie J. , Bateup Helen S. 
Published: November 2021

AbstractThe mTOR pathway is an essential regulator of cell growth and metabolism. Midbrain dopamine neurons are particularly sensitive to mTOR signaling status as activation or inhibition of mTOR alters their morphology and physiology. mTOR exists in two distinct multiprotein complexes termed mTORC1 and mTORC2. How each of these complexes affect dopamine neuron properties and whether they act together or independently is unknown. Here we investigated this in mice with dopamine neuron-specific deletion of Rptor or Rictor, which encode obligatory components of mTORC1 or mTORC2, respectively. We find that inhibition of mTORC1 strongly and broadly impacts dopamine neuron structure and function causing somatodendritic and axonal hypotrophy, increased intrinsic excitability, decreased dopamine production, and impaired dopamine release. In contrast, inhibition of mTORC2 has more subtle effects, with selective alterations to the output of ventral tegmental area dopamine neurons. As mTOR is involved in several brain disorders caused by dopaminergic dysregulation including Parkinson’s disease and addiction, our results have implications for understanding the pathophysiology and potential therapeutic strategies for these diseases.
Neuronal origins of biases in economic choices under sequential offers
Authors: Shi Weikang , Ballesta Sébastien , Padoa-Schioppa Camillo 
Published: November 2021

AbstractEconomic choices are characterized by a variety of biases. Understanding their origins is a long-term goal for neuroeconomics, but progress on this front has been limited. Here we examined choice biases observed when two goods are offered sequentially. In the experiments, rhesus monkeys chose between different juices offered simultaneously or in sequence. Choices under sequential offers were less accurate (higher variability). They were also biased in favor of the second offer (order bias) and in favor of the preferred juice (preference bias). Analysis of neuronal activity recorded in orbitofrontal cortex revealed that these phenomena emerged at different computational stages. The lower choice accuracy reflected weaker offer value signals (valuation stage), the order bias emerged during value comparison (decision stage), and the preference bias emerged late in the trial (post-comparison). Our approach, leveraging recent notions on the neural mechanisms of economic decisions, may shed light on other aspects of choice behavior.
Defining the determinants of under-vaccination in migrant populations in Europe to improve routine and COVID-19 vaccine uptake: a systematic review
Authors: Crawshaw Alison F , Farah Yasmin , Deal Anna , Rustage Kieran , Hayward Sally E , Carter Jessica , Knights Felicity , Goldsmith Lucy P , Campos-Matos Ines , Wurie Fatima , Majeed Azeem , Bedford Helen , Forster Alice S , Hargreaves Sally 
Published: November 2021

AbstractDiverse migrant populations in Europe are at risk of under-immunisation and have recently shown lower levels of COVID-19 vaccination intent and uptake. Understanding the determinants of vaccine uptake in migrants is critical to address immediate COVID-19 vaccination inequities, and longer-term will help improve coverage for routine vaccinations, aligning with the goals of the new Immunisation Agenda 2030. We did a systematic review following PRISMA guidelines and using a PICOS framework (PROSPERO CRD42020219214; MEDLINE, CINAHL, PsycINFO databases, 1 January 2000 – 14 September 2021) exploring barriers and facilitators to vaccine uptake and determinants of under-vaccination in migrants in the EU/EEA, UK, and Switzerland. We categorised barriers/facilitators using the ‘5As’ Determinants of Vaccine Uptake Taxonomy. 5259 data sources were screened, with 67 studies included from 16 countries, representing 366,529 migrants. Access barriers were most commonly reported (language, literacy and communication barriers; practical and legal barriers to accessing/delivering vaccination services; service barriers, including lack of specific guidelines and knowledge of healthcare professionals) for key vaccines including MMR, DTP, HPV, influenza, polio, COVID-19 vaccines. Acceptance barriers were mostly reported in Eastern European and Muslim communities for HPV, measles, and influenza vaccines. We identified 23 determinants of under-vaccination in migrants, including geographical origin (where 25/26 (96%) studies showed significance) – particularly African/Eastern European origin; recent migration; being a refugee/asylum seeker; higher income; parental education level; no healthcare contact in the past year; and lower language skills. Facilitators of migrants’ vaccine uptake included tailored vaccination messaging, community outreach and ‘nudging’ interventions. Migrants’ barriers to accessing healthcare are already well documented, and this review confirms their role in limiting vaccine uptake. These data hold immediate relevance to strengthening vaccination programmes in high-income countries, including for COVID-19. Our findings suggested that targeted, evidence-informed strategies are needed to address access and acceptance barriers to vaccination in migrants, including the development of migrant-sensitive and adaptable vaccination services and systems, unambiguous public health messaging, and coproduction of tailored interventions.
From group to individual - Genotyping by pool sequencing eusocial colonies
Authors: Eynard Sonia E , Vignal Alain , Basso Benjamin , Le Conte Yves , Decourtye Axel , Genestout Lucie , Labarthe Emmanuelle , Mondet Fanny , Tabet Kamila , Servin Bertrand 
Published: November 2021

AbstractBackgroundEusocial insects play a central role in many ecosystems, and particularly the important pollinator honeybee (Apis mellifera). One approach to facilitate their study in molecular genetics, is to consider whole colonies as single individuals by combining DNA of multiple individuals in a single pool sequencing experiment. Such a technique comes with the drawback of producing data requiring dedicated analytical methods to be fully exploited. Despite this limitation, pool sequencing data has been shown to be informative and cost-effective when working on random mating populations. Here, we present new statistical methods for exploiting pool sequencing data of eusocial colonies in order to reconstruct the genotype of the colony founder, the queen. This leverages the possibility to monitor genetic diversity, perform genomic-based studies or implement selective breeding.ResultsUsing simulations and honeybee real data, we show that the methods allow for a fast and accurate estimation of the genetic ancestry, with correlations of 0.9 with that obtained from individual genotyping, and for an accurate reconstruction of the queen genotype, with 2% genotyping error. We further validate the inference using experimental data on colonies with both pool sequencing and individual genotyping of drones.ConclusionIn this study we present statistical models to accurately estimate the genetic ancestry and reconstruct the genotype of the queen from pool sequencing data from workers of an eusocial colony. Such information allows to exploit pool sequencing for traditional population genetics, association studies and selective breeding. While validated in Apis mellifera, these methods are applicable to other eusocial hymenoptera species.
Generation of a mitochondrial protein compendium in Dictyostelium discoideum
Authors: Freitas Anna V , Herb Jake T , Pan Miao , Cheng Yong , Gucek Marjan , Jin Tian , Xu Hong 
Published: November 2021

AbstractThe social amoeba Dictyostelium discoideum is a well-established model to study numerous cellular processes including cell motility, chemotaxis, and differentiation. As energy metabolism is involved in these processes, mitochondrial genetics and bioenergetics are of interest, though many features of Dictyostelium mitochondria differ from metazoans. A comprehensive inventory of mitochondrial proteins is critical to understanding mitochondrial processes and their involvement in various cellular pathways. Here, we utilized high-throughput multiplexed protein quantitation and homology analyses to generate a high-confidence mitochondrial protein compendium. Our proteomic approach, which utilizes quantitative mass spectrometry in combination with mathematical modeling, was validated through mitochondrial targeting sequence prediction and live-cell imaging. Our final compendium consists of 1082 proteins. Within our D. discoideum mitochondrial proteome, we identify many proteins that are not present in humans, yeasts, or the ancestral alpha-proteobacteria, which can serve as a foundation for future investigations into the unique mitochondria of Dictyostelium. Additionally, we leverage our compendium to highlight the complexity of metabolic reprogramming during starvation-induced development. Our compendium lays a foundation to investigate mitochondrial processes that are unique in protists, as well as for future studies to understand the functions of conserved mitochondrial proteins in health and diseases using D. discoideum as the model.
Modelling novelty detection in the thalamocortical loop
Authors: Han Chao , English Gwendolyn , Saal Hannes P. , Indiveri Giacomo , Gilra Aditya , von der Behrens Wolfger , Vasilaki Eleni 
Published: November 2021

AbstractIn complex natural environments, sensory systems are constantly exposed to a large stream of inputs. Novel or rare stimuli, which are often associated with behaviorally important events, are typically processed differently than the steady sensory background, which has less relevance. Neural signatures of such differential processing, commonly referred to as novelty detection, have been identified on the level of EEG recordings as mismatch negativity and the level of single neurons as stimulus-specific adaptation. Here, we propose a multi-scale recurrent network with synaptic depression to explain how novelty detection can arise in the whisker-related part of the somatosensory thalamocortical loop. The architecture and dynamics of the model presume that neurons in cortical layer 6 adapt, via synaptic depression, specifically to a frequently presented stimulus, resulting in reduced population activity in the corresponding cortical column when compared with the population activity evoked by a rare stimulus. This difference in population activity is then projected from the cortex to the thalamus and amplified through the interaction between neurons of the primary and reticular nuclei of the thalamus, resulting in spindle-like, rhythmic oscillations. These differentially activated thalamic oscillations are forwarded to cortical layer 4 as a late secondary response that is specific to rare stimuli that violate a particular stimulus pattern. Model results show a strong analogy between this late single neuron activity and EEG-based mismatch negativity in terms of their common sensitivity to presentation context and timescales of response latency, as observed experimentally. Our results indicate that adaptation in L6 can establish the thalamocortical dynamics that produce signatures of SSA and MMN and suggest a mechanistic model of novelty detection that could generalize to other sensory modalities.Author summaryCortical sensory neurons have been shown to be capable of novelty detection, that is they respond more vigorously when a novel, unexpected stimulus is presented, and less so when the stimulus is part of a predictable sequence. However, the neural mechanism underlying this capability is not yet fully understood. Here, we developed a thalamocortical network model that accounts for novelty detection and reproduces physiologically observed neural response patterns in the somatosensory cortex. Specifically, our results demonstrate that the novelty signal arises from the complex recurrent interplay between thalamic neurons and cortical neurons in layers 4 and 6. This work therefore provides a concrete mechanism that can serve as a starting point for further investigating the neural circuit mechanisms underlying novelty detection.
Light contamination in stable isotope-labelled internal peptide standards is frequent and a potential source of false discovery and quantitation error in proteomics
Authors: Salek Mogjiborahman , Förster Jonas D. , Lehmann Wolf-Dieter , Riemer Angelika B. 
Published: November 2021

ABSTRACTIn mass spectrometry-based proteomics, heavy internal standards are used to validate target peptide detections and to calibrate peptide quantification. Here we report light contamination present in heavy labelled synthetic peptides of high isotopic enrichment. Application of such peptides as assay-internal standards potentially compromises the detection and quantification especially of low abundant cellular peptides. Therefore, it is important to adopt guidelines to prevent false-positive identifications of endogenous light peptides as well as errors in their quantification from biological samples.