bluuebunny/crossref_metadata_2025 huggingface dataset:
Do human butchery patterns exist? A study of the interaction of randomness and channelling in the distribution of cut marks on long bones
Authors: Pizarro-Monzo Marcos , Prendergast Mary E. , Gidna Agness O. , Baquedano Enrique , Mora Rocio , Gonzalez-Aguilera Diego , Mate-Gonzalez Miguel A. , Domínguez-Rodrigo Manuel
Published: January 2021

Bone surface modifications (BSMs) in faunal assemblages are frequently used to infer past agency and actions of hominins and carnivores, with implications for the emergence of key human behaviours. Patterning of BSMs has mostly been defined as a combination of the intensity of marks per bone portion and sometimes per element. Numerous variables involved in butchery can condition cut mark anatomical distribution, so much so that these variables are widely assumed to be stochastic. Here, we present a new methodological approach using a novel geospatial tool (Ikhnos) which combines the three-dimensional spatial documentation of cut mark patterns with spatial statistics based on wavelets, applied to three experimental and ethnoarchaeological faunal assemblages. We use wavelets to identify patterning of multiple longitudinal series of cut mark distributions on bones, and to establish similarities or differences in patterning within and across different assemblages. This method demonstrates the existence of general and behaviour-specific butchery patterns. It can also be used to effectively assess the proportion of mark clustering that is due to randomness, versus that which is conditioned by the butchery process.
Schwann cell remyelination of the central nervous system: why does it happen and what are the benefits?
Authors: Chen Civia Z. , Neumann Björn , Förster Sarah , Franklin Robin J. M.
Published: January 2021

Myelin sheaths, by supporting axonal integrity and allowing rapid saltatory impulse conduction, are of fundamental importance for neuronal function. In response to demyelinating injuries in the central nervous system (CNS), oligodendrocyte progenitor cells (OPCs) migrate to the lesion area, proliferate and differentiate into new oligodendrocytes that make new myelin sheaths. This process is termed remyelination. Under specific conditions, demyelinated axons in the CNS can also be remyelinated by Schwann cells (SCs), the myelinating cell of the peripheral nervous system. OPCs can be a major source of these CNS-resident SCs—a surprising finding given the distinct embryonic origins, and physiological compartmentalization of the peripheral and central nervous system. Although the mechanisms and cues governing OPC-to-SC differentiation remain largely undiscovered, it might nevertheless be an attractive target for promoting endogenous remyelination. This article will (i) review current knowledge on the origins of SCs in the CNS, with a particular focus on OPC to SC differentiation, (ii) discuss the necessary criteria for SC myelination in the CNS and (iii) highlight the potential of using SCs for myelin regeneration in the CNS.
Learning functionals via LSTM neural networks for predicting vessel dynamics in extreme sea states
Authors: del Águila Ferrandis J. , Triantafyllou M. S. , Chryssostomidis C. , Karniadakis G. E.
Published: January 2021

Predicting motions of vessels in extreme sea states represents one of the most challenging problems in naval hydrodynamics. It involves computing complex nonlinear wave-body interactions, hence taxing heavily computational resources. Here, we put forward a new simulation paradigm by training recurrent type neural networks (RNNs) that take as input the stochastic wave elevation at a certain sea state and output the main vessel motions, e.g. pitch, heave and roll. We first compare the performance of standard RNNs versus GRU and LSTM neural networks (NNs) and show that LSTM NNs lead to the best performance. We then examine the testing error of two representative vessels, a catamaran in sea state 1 and a battleship in sea state 8. We demonstrate that good accuracy is achieved for both cases in predicting the vessel motions for unseen wave elevations. We train the NNs with expensive CFD simulations
offline
, but upon training, the prediction of the vessel dynamics
online
can be obtained at a fraction of a second. This work is motivated by the universal approximation theorem for functionals (Chen & Chen, 1993.
IEEE Trans. Neural Netw.
4
, 910–918 (
doi:10.1109/72.286886
)), and it is the first implementation of such theory to realistic engineering problems.
Nonlinear viscoelasticity of strain rate type: an overview
Authors: Şengül Yasemin
Published: January 2021

There are some materials in nature that experience deformations that are not elastic. Viscoelastic materials are some of them. We come across many such materials in our daily lives through a number of interesting applications in engineering, material science and medicine. This article concerns itself with modelling of the nonlinear response of a class of viscoelastic solids. In particular, nonlinear viscoelasticity of strain rate type, which can be described by a constitutive relation for the stress function depending not only on the strain but also on the strain rate, is considered. This particular case is not only favourable from a mathematical analysis point of view but also due to experimental observations, knowledge of the strain rate sensitivity of viscoelastic properties is crucial for accurate predictions of the mechanical behaviour of solids in different areas of applications. First, a brief introduction of some basic terminology and preliminaries, including kinematics, material frame-indifference and thermodynamics, is given. Then, considering the governing equations with constitutive relationships between the stress and the strain for the modelling of nonlinear viscoelasticity of strain rate type, the most general model of interest is obtained. Then, the long-term behaviour of solutions is discussed. Finally, some applications of the model are presented.
A super Degasperis–Procesi equation and related integrable systems
Authors: Gao Binfang , Tian Kai , Liu Qing Ping
Published: January 2021

Based on a 4 × 4 matrix spectral problem, a super Degasperis–Procesi (DP) equation is proposed. We show that under a reciprocal transformation, the super DP equation is related to the first negative flow of a super Kaup–Kupershmidt (KK) hierarchy, which turns out to be a particular reduction of a super Boussinesq hierarchy. The bi-Hamiltonian structure of the super Boussinesq hierarchy is established and subsequently produces a Hamiltonian structure, as well as a conjectured symplectic formulation of the super KK hierarchy via suitable reductions. With the help of the reciprocal transformation, the bi-Hamiltonian representation of the super DP equation is constructed from that of the super KK hierarchy. We also calculate a positive flow of the super DP hierarchy and explain its relations with the super KK equation. Infinitely many conservation laws are derived for the super DP equation, as well as its positive flow.
Aerial photogrammetry and tag-derived tissue density reveal patterns of lipid-store body condition of humpback whales on their feeding grounds
Authors: Aoki Kagari , Isojunno Saana , Bellot Charlotte , Iwata Takashi , Kershaw Joanna , Akiyama Yu , Martín López Lucía M. , Ramp Christian , Biuw Martin , Swift René , Wensveen Paul J. , Pomeroy Patrick , Narazaki Tomoko , Hall Ailsa , Sato Katsufumi , Miller Patrick J. O.
Published: January 2021

Monitoring the body condition of free-ranging marine mammals at different life-history stages is essential to understand their ecology as they must accumulate sufficient energy reserves for survival and reproduction. However, assessing body condition in free-ranging marine mammals is challenging. We cross-validated two independent approaches to estimate the body condition of humpback whales (Megaptera novaeangliae) at two feeding grounds in Canada and Norway: animal-borne tags (n= 59) and aerial photogrammetry (n= 55). Whales that had a large length-standardized projected area in overhead images (i.e. whales looked fatter) had lower estimated tissue body density (TBD) (greater lipid stores) from tag data. Linking both measurements in a Bayesian hierarchical model to estimate the true underlying (hidden) tissue body density (uTBD), we found uTBD was lower (−3.5 kg m−3) in pregnant females compared to adult males and resting females, while in lactating females it was higher (+6.0 kg m−3). Whales were more negatively buoyant (+5.0 kg m−3) in Norway than Canada during the early feeding season, possibly owing to a longer migration from breeding areas. While uTBD decreased over the feeding season across life-history traits, whale tissues remained negatively buoyant (1035.3 ± 3.8 kg m−3) in the late feeding season. This study adds confidence to the effectiveness of these independent methods to estimate the body condition of free-ranging whales.
Coevolution of female fidelity and male help in populations with alternative reproductive tactics
Authors: Li Xiang-Yi , Morozov Andrew , Goymann Wolfgang
Published: January 2021

In socially monogamous species, pair-bonded males often continue to provide care to all offspring in their nests despite some degree of paternity loss due to female extra-pair copulation. Previous theoretical models suggested that females can use their within-pair offspring as ‘hostages' to blackmail their social mates, so that they continue to provide care to the brood at low levels of cuckoldry. These models, however, rely on the assumption of sufficiently accurate male detection of cuckoldry and the reduction of parental effort in case of suspicion. Therefore, they cannot explain the abundant cases where cuckolded males continue to provide extensive care to the brood. Here we use an analytical population genetics model and an individual-based simulation model to explore the coevolution of female fidelity and male help in populations with two genetically determined alternative reproductive tactics (ARTs): sneakers that achieve paternity solely via extra-pair copulations and bourgeois that form a mating pair and spend some efforts in brood care. We show that when the efficiency of mate guarding is intermediate, the bourgeois males can evolve to ‘specialize' in providing care by spending more than 90% of time in helping their females while guarding them as much as possible, despite frequent cuckoldry by the sneakers. We also show that when sneakers have tactic-specific adaptations and thus are more competitive than the bourgeois in gaining extra-pair fertilizations, the frequency of sneakers and the degrees of female fidelity and male help can fluctuate in evolutionary cycles. Our theoretical predictions highlight the need for further empirical tests in species with ARTs.
Bilateral amygdala damage linked to impaired ability to predict others' fear but preserved moral judgements about causing others fear
Authors: Cardinale Elise M. , Reber Justin , O'Connell Katherine , Turkeltaub Peter E. , Tranel Daniel , Buchanan Tony W. , Marsh Abigail A.
Published: January 2021

The amygdala is a subcortical structure implicated in both the expression of conditioned fear and social fear recognition. Social fear recognition deficits following amygdala lesions are often interpreted as reflecting perceptual deficits, or the amygdala's role in coordinating responses to threats. But these explanations fail to capture why amygdala lesions impair both physiological and behavioural responses to multimodal fear cues and the ability to identify them. We hypothesized that social fear recognition deficits following amygdala damage reflect impaired conceptual understanding of fear. Supporting this prediction, we found specific impairments in the ability to predict others' fear (but not other emotions) from written scenarios following bilateral amygdala lesions. This finding is consistent with the suggestion that social fear recognition, much like social recognition of states like pain, relies on shared internal representations. Preserved judgements about the permissibility of causing others fear confirms suggestions that social emotion recognition and morality are dissociable.
Anacraspedodidymum submersum sp. nov. (Chaetosphaeriaceae, Chaetosphaeriales), a new species of freshwater hyphomycetes from southwest China
Authors: Zheng Hua , Li Jie , Guo Ji-Shu , Qiao Min , Yu Ze-Fen
Published: January 2021

During a mycological survey of freshwater hyphomycetes on submerged leaves in southwest China, a new species, Anacraspedodidymum submersum, was isolated. The new species A. submersum is characterized by having monophialidic conidiogenous cells with funnel shaped collarettes and globose or subglobose, aseptate and hyaline conidia. Morphologically, A. submersum is somewhat similar to A. aquaticum and A. hyalosporum in conidiophores and conidiogenous cells, but can be easily distinguished by its subglobose to globose and smaller conidia. Phylogenetic analysis of combined ITS and LSU sequences show that the new species of Anacraspedodidymum clustered together with the genus Thozetella in Chaetosphaeriaceae. A full description, illustrations and a phylogenetic tree showing the position of A. submersum are provided herein.
Pedobacter gandavensis sp. nov., Pedobacter foliorum sp. nov. and Pedobacter planticolens sp. nov., isolated from leaves of Arabidopsis thaliana
Authors: Qi Shan Shan , Cnockaert Margo , Carlier Aurélien , Vandamme Peter
Published: January 2021

Three rod-shaped, non-spore-forming, yellow or pale-yellow pigmented bacteria with distinct MALDI-TOF mass spectra were isolated from the phyllosphere of Arabidopsis thaliana seedlings. Their 16S rRNA gene sequences demonstrated that these isolates belong to the genus

Pedobacter

. The nearest phylogenetic neighbours of strain LMG 31462T were

Pedobacter steynii

DSM 19110T (98.3 % 16S rRNA sequence similarity) and

Pedobacter caeni

LMG 22862T (98.3 %); the nearest phylogenetic neighbours of strain LMG 31463T were

Pedobacter panaciterrae

Gsoil 042T (98.3 %) and

Pedobacter nutrimenti

DSM 27372T (98.1 %); and the nearest phylogenetic neighbours of strain LMG 31464T were

Pedobacter boryungensis

BR-9T (99.0 %) and

Pedobacter daejeonensis

THG-DN3.18T (98.7 %). Average nucleotide identity analyses between the whole genome sequences of the three strains and of the type strains of their respective nearest-neighbour taxa yielded values well below the species delineation threshold and thus confirmed that the three strains represented a novel

Pedobacter

species each. An extensive phenotypic comparison and an analysis of whole-cell fatty acid components yielded distinctive phenotypic characteristics for each of these strains. We therefore propose to classify these isolates as three novel species, for which we propose the names Pedobacter gandavensis with LMG 31462T (=R-74704T=CECT 30149T) as the type strain, Pedobacter foliorum with LMG 31463T (=R-74623T=CECT 30150T) as the type strain and Pedobacter planticolens with LMG 31464T (=R-74626T=CECT 30151T) as the type strain.
Acquisition of pcnB [poly(A) polymerase I] genes via horizontal transfer from the β, γ-Proteobacteria
Authors: Jones George H.
Published: January 2021

Poly(A) polymerases (PAPs) and tRNA nucleotidyltransferases belong to a superfamily of nucleotidyltransferases and modify RNA 3′-ends. The product of the pcnB gene, PAP I, has been characterized in a few β-, γ- and δ-

Proteobacteria

. Using the PAP I signature sequence, putative PAPs were identified in bacterial species from the α- and ε-

Proteobacteria

and from four other bacterial phyla (

Firmicutes

,

Actinobacteria

,

Bacteroidetes

and

Aquificae

). Phylogenetic analysis, alien index and G+C content calculations strongly suggest that the PAPs in the species identified in this study arose by horizontal gene transfer from the β- and γ-

Proteobacteria

.
Non-invasive Diagnosis of Deep Vein Thrombosis from Ultrasound with Machine Learning
Authors: Kainz Bernhard , Makropoulos Antonios , Oppenheimer Jonas , Deane Christopher , Mischkewitz Sven , Al-Noor Fouad , Rawdin Andrew C , Stevenson Matthew D , Mandegaran Ramin , Heinrich Mattias P. , Curry Nicola
Published: January 2021

Deep Vein Thrombosis (DVT) is a blood clot most found in the leg, which can lead to fatal pulmonary embolism (PE). Compression ultrasound of the legs is the diagnostic gold standard, leading to a definitive diagnosis. However, many patients with possible symptoms are not found to have a DVT, resulting in long referral waiting times for patients and a large clinical burden for specialists. Thus, diagnosis at the point of care by non-specialists is desired.

We collect images in a pre-clinical study and investigate a deep learning approach for the automatic interpretation of compression ultrasound images. Our method provides guidance for free-hand ultrasound and aids non-specialists in detecting DVT.

We train a deep learning algorithm on ultrasound videos from 246 healthy volunteers and evaluate on a sample size of 51 prospectively enrolled patients from an NHS DVT diagnostic clinic. 32 DVT-positive patients and 19 DVT-negative patients were included. Algorithmic DVT diagnosis results in a sensitivity of 93.8% and a specificity of 84.2%, a positive predictive value of 90.9%, and a negative predictive value of 88.9% compared to the clinical gold standard.

To assess the potential benefits of this technology in healthcare we evaluate the entire clinical DVT decision algorithm and provide cost analysis when integrating our approach into a diagnostic pathway for DVT. Our approach is estimated to be cost effective at up to $150 per software examination, assuming a willingness to pay $26 000/QALY.
Engineering a niche supporting haematopoietic stem cell development using integrated single cell transcriptomics
Authors: Hadland Brandon , Varnum-Finney Barbara , Dozono Stacey , Dignum Tessa , Nourigat-McKay Cynthia , Jackson Dana L , Itkin Tomer , Butler Jason M. , Rafii Shahin , Trapnell Cole , Bernstein Irwin D.
Published: January 2021

Haematopoietic stem cells (HSCs) develop from haemogenic endothelium (HE) within embryonic arterial vessels such as the aorta of the aorta-gonad-mesonephros region (AGM). To identify the signals responsible for HSC formation, we used single cell RNA-sequencing to simultaneously analyze the transcriptional profiles of AGM-derived cells transitioning from HE to HSC, and AGM-derived endothelial cells which provide signals sufficient to support HSC maturation and self-renewal. Pseudotemporal ordering revealed dynamics of gene expression during the HE to HSC transition, identifying surface receptors specifically expressed on developing HSCs. Transcriptional profiles of niche endothelial cells enabled identification of corresponding ligands, including those signaling to Notch receptors, VLA-4 integrin, and CXCR4, which, when integrated in an engineered platform, were sufficient to support the generation of engrafting HSCs. These studies provide a transcriptional map of the signaling interactions necessary for the development of HSCs and advance the goal of engineering HSC for therapeutic applications.
Opposing mechanisms of competition determine species invasions and functional diversity
Authors: Wong Mark K. L. , Lee Roger H. , Leong Chi-Man , Lewis Owen T. , Guénard Benoit
Published: January 2021

Understanding how species’ phenotypic differences affect competition is key to explaining community assembly and predicting biodiversity responses. Many studies overlook the variable effects that species’ trait differences can have on the direction of competitive exclusion, which reverses depending on the specific mechanism at play. We performed a comprehensive trait-based study of an ant invasion integrating morphological, dietary, physiological and behavioral analyses. We found that trait differences between invasive and resident species were not only associated with niche differences which promoted the coexistence of dissimilar species, but also competitive ability differences which acted in the opposite fashion. Furthermore, competition along separate trait axes led to complex and contrasting patterns in the invaded assemblages, where species were at once similar (clustered) in some traits but also dissimilar (overdispersed) in others. Our results reveal that different aspects of phenotype may distinctly modulate the effect of competition in structuring ecological communities and functional diversity.
Intrinsic reinstatement of induced oscillatory context
Authors: Chantrel Yoann , Trabattoni Valeria , Orton Lydia , Javadi Amir-Homayoun
Published: January 2021

Declarative memory retrieval is thought to rely on the reinstatement, at retrieval, of contextual cues present during encoding, as evidenced in the context and state-dependent literature. Specifically, previous work has shown that reinstating the oscillatory activity present during encoding, at retrieval, is particularly supportive of memory recall. Our study builds on previous findings suggesting that the oscillatory activity present at encoding may be automatically reinstated during retrieval. To explore the roles of consolidation, prefrontal involvement, and frequency specific activity in this process of oscillatory reinstatement, 115 healthy young adults were randomly assigned to one of five conditions. In each condition, transcranial alternating current stimulation (tACS) was administered at either one of two frequencies (60Hz or 6Hz), over the left dorsolateral prefrontal cortex (left-DLPFC, Experimental) or the right primary motor cortex (right-PMC, Control), during learning of written words. This was followed by a retention interval of either 90 minutes or 1 week and a testing phase, during which EEG activity was recorded. Our results showed significant (and frequency specific) oscillatory reinstatement, after stimulation of the left-DLPFC, in the 1-week retention condition. Oscillatory reinstatement effects were non-significant after stimulation of the right-PMC, or in the 90 minutes retention interval condition. Our results highlight that the oscillatory activity induced during encoding is consolidated as context alongside the information and is reinstated intrinsically during retrieval. The implications of our findings for models of human memory, future avenues of research and clinical applications are discussed.
Efficient Precision Dosing Under Estimated Uncertainties via Koopman Expectations of Bayesian Posteriors with Pumas
Authors: Rackauckas Chris , Dixit Vaibhav , Gerlach Adam R. , Ivaturi Vijay
Published: January 2021

Personalized precision dosing is about mathematically determining effective dosing strategies that optimize the probability of containing a patient’s outcome within a therapeutic window. However, the common Monte Carlo approach for generating patient statistics is computationally expensive because thousands of simulations need to be computed. In this manuscript we describe a new method which utilizes the Koopman operator to perform a direct computation of expected patient outcomes with respect to quantified uncertainties of Bayesian posteriors in a nonlinear mixed effect model framework. We detail how quantities such as the probability of being within the therapeutic window can be calculated with a choice of loss function on the Koopman expectation. We demonstrate a high performance parallelized implementation of this methodology in Pumas®and showcase the ability to accelerate the computation of these expectations by 50x-200x over Monte Carlo. We showcase how dosing can be optimized with respect to probabilistic statements respecting variable uncertainties using the Koopman operator. We end by demonstrating an end-to-end workflow, from estimating variable uncertainties via Bayesian estimation to optimizing a dose with respect to parametric uncertainty.
Network-based analysis of allele frequency distribution among multiple populations identifies adaptive genomic structural variants
Authors: Saitou Marie. , Masuda Naoki , Gokcumen Omer.
Published: January 2021

Structural variants have a considerable impact on human genomic diversity. However, their evolutionary history remains mostly unexplored. Here, we developed a new method to identify potentially adaptive structural variants based on a network-based analysis that incorporates genotype frequency data from 26 populations simultaneously. Using this method, we analyzed 57,629 structural variants and identified 577 structural variants that show high population distribution. We further showed that 39 and 20 of these putatively adaptive structural variants overlap with coding sequences or are significantly associated with GWAS traits, respectively. Closer inspection of the haplotypic variation associated with these putatively adaptive and functional structural variants reveals deviations from neutral expectations due to (i) population differentiation of rapidly evolving multi-allelic variants, (ii) incomplete sweeps, and (iii) recent population-specific negative selection. Overall, our study provides new methodological insights, documents hundreds of putatively adaptive variants, and introduces evolutionary models that may better explain the complex evolution of structural variants.
The urea cycle is transcriptionally controlled by hypoxia-inducible factors
Authors: Singh Charandeep , Benos Andrew , Grenell Allison , Tran Vincent , Hanna Demiana , Anand-Apte Bela , Brunengraber Henri , Sears Jonathan E.
Published: January 2021

Here, we demonstrate transcriptional regulation of urea cycle genes CPS1 and ARG1 by hypoxia-inducible factors (HIFs) and demonstrate a hepatic HIF dependent increase in urea cycle activity.
Ecology of active viruses and their bacterial hosts in frozen Arctic peat soil revealed with H218O stable isotope probing metagenomics
Authors: Trubl Gareth , Kimbrel Jeffrey A. , Liquet-Gonzalez Jose , Nuccio Erin E. , Weber Peter K. , Pett-Ridge Jennifer , Jansson Janet K. , Waldrop Mark P. , Blazewicz Steven J.
Published: January 2021

Winter carbon loss in northern ecosystems is estimated to be greater than the average growing season carbon uptake. However, most ecosystem carbon measurements neglect winter months since carbon losses (primarily driven by microbial decomposers) are assumed to be negligible at low temperatures. We used stable isotope probing (SIP) targeted metagenomics to reveal the genomic potential of active soil microbial populations under winter conditions, with an emphasis on viruses and virus-host dynamics. Peat soils from the Bonanza Creek LTER site in Alaska were incubated under subzero anoxic conditions with H218O for 184 and 370 days. We identified 46 bacterial populations (MAGs; spanning 9 bacterial phyla) and 243 viral populations (vOTUs) that actively took up18O and produced significant CO2throughout the incubation. Active hosts, predicted for 33% of the active vOTUs, were some of the most abundant MAGs and capable of fermentation and organic matter degradation. Approximately three-quarters of the active vOTUs carried auxiliary metabolic genes that spanned five functional categories, including carbon utilization, highlighting the potential impact of viruses in this peat soil’s microbial biogeochemistry. These results illustrate significant bacterial and viral activity and interactions occur in frozen soils, revealing viruses are a major community-structuring agent throughout winter months.
Detour learning ability and the effect of novel sensory cues on learning in Australian bull ants,Myrmecia midas
Authors: Islam Muzahid , Deeti Sudhakar , Mahmudah Zakia , Kamhi J. Frances , Cheng Ken
Published: January 2021

Many animals navigate in a structurally complex environment which requires them to detour around physical barriers that they encounter. While many studies in animal cognition suggest that they are able to adeptly avoid obstacles, it is unclear whether a new route is learned to navigate around these barriers and, if so, what sensory information may be used to do so. We investigated detour learning ability in the Australian bull ant,Myrmecia midas, which primarily uses visual landmarks to navigate. We first placed a barrier on the ants’ natural path of their foraging tree. Initially, 46% of foragers were unsuccessful in detouring the obstacle. In subsequent trips, the ants became more successful and established a new route. We observed up to eight successful foraging trips detouring around the barrier. When we subsequently changed the position of the barrier, made a new gap in the middle of the obstacle, or removed the barrier altogether, ants mostly maintained their learned motor routine, detouring with a similar path as before, suggesting that foragers were not relying on barrier cues and therefore learned a new route around the obstacle. In additional trials, when foragers encountered new olfactory or tactile cues, or the visual environment was blocked, their navigation was profoundly disrupted. These results suggest that changing sensory information, even in modalities that foragers do not usually need for navigation, drastically affects the foragers’ ability to successful navigate.

Subject Category

Neuroscience and Cognition
Lack of trust and social media echo chambers predict COVID-19 vaccine hesitancy
Authors: Jennings Will , Stoker Gerry , Willis Hannah , Valgardsson Viktor , Gaskell Jen , Devine Daniel , McKay Lawrence , Mills Melinda C.
Published: January 2021

As COVID-19 vaccines are rolled out across the world, there are growing concerns about the role that trust, belief in conspiracy theories and spread of misinformation through social media impact vaccine hesitancy. We use a nationally representative survey of 1,476 adults in the UK between December 12 to 18, 2020 and five focus groups conducted in the same period. Trust is a core predictor, with distrust in vaccines in general and mistrust in government raising vaccine hesitancy. Trust in health institutions and experts and perceived personal threat are vital, with focus groups revealing that COVID-19 vaccine hesitancy is driven by a misunderstanding of herd immunity as providing protection, fear of rapid vaccine development and side effects, belief the virus is man- made and related to population control. Particularly those who obtain information from relatively unregulated social media sources such as YouTube that have recommendations tailored by watch history are less likely to be willing to become vaccinated. Those who hold general conspiratorial beliefs are less willing to be vaccinated. Since an increasing number of individuals use social media for gathering health information, interventions require action from governments, health officials and social media companies. More attention needs to help people understand their own risks, unpack complex concepts and fill knowledge voids.
Efficacy of Colchicine in Non-Hospitalized Patients with COVID-19
Authors: Tardif Jean-Claude , Bouabdallaoui Nadia , L’Allier Philippe L. , Gaudet Daniel , Shah Binita , Pillinger Michael H. , Lopez-Sendon Jose , da Luz Protasio , Verret Lucie , Audet Sylvia , Dupuis Jocelyn , Denault André , Pelletier Martin , Tessier Philippe A. , Samson Sarah , Fortin Denis , Tardif Jean-Daniel , Busseuil David , Goulet Elisabeth , Lacoste Chantal , Dubois Anick , Joshi Avni Y. , Waters David D. , Hsue Priscilla , Lepor Norman E. , Lesage Frédéric , Sainturet Nicolas , Roy-Clavel Eve , Bassevitch Zohar , Orfanos Andreas , Grégoire Jean C. , Busque Lambert , Lavallée Christian , Hétu Pierre-Olivier , Paquette Jean-Sébastien , Levesque Sylvie , Cossette Mariève , Nozza Anna , Chabot-Blanchet Malorie , Dubé Marie-Pierre , Guertin Marie-Claude , Boivin Guy ,   for the COLCORONA Investigators
Published: January 2021

Background

Evidence suggests the role of an inflammatory storm in COVID-19 complications. Colchicine is an orally administered, anti-inflammatory medication beneficial in gout, pericarditis and coronary disease.

Methods

We performed a randomized, double-blind trial involving non-hospitalized patients with COVID-19 diagnosed by polymerase chain reaction (PCR) testing or clinical criteria. The patients were randomly assigned to receive colchicine (0.5 mg twice daily for 3 days and once daily thereafter) or placebo for 30 days. The primary efficacy endpoint was the composite of death or hospitalization for COVID-19.

Results

A total of 4488 patients were enrolled. The primary endpoint occurred in 4.7% of the patients in the colchicine group and 5.8% of those in the placebo group (odds ratio, 0.79; 95.1% confidence interval (CI), 0.61 to 1.03; P=0.08). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 4.6% and 6.0% of patients in the colchicine and placebo groups, respectively (odds ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04). In these patients with PCR-confirmed COVID-19, the odds ratios were 0.75 (95% CI, 0.57 to 0.99) for hospitalization due to COVID-19, 0.50 (95% CI, 0.23 to 1.07) for mechanical ventilation, and 0.56 (95% CI, 0.19 to 1.66) for death. Serious adverse events were reported in 4.9% and 6.3% in the colchicine and placebo groups (P=0.05); pneumonia occurred in 2.9% and 4.1% of patients (P=0.02). Diarrhea was reported in 13.7% and 7.3% in the colchicine and placebo groups (P<0.0001).

Conclusion

Among non-hospitalized patients with COVID-19, colchicine reduces the composite rate of death or hospitalization. (COLCORONAClinicalTrials.govnumber:NCT04322682)
The Association Between Hypoglycemic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis
Authors: Han Tiantian , Ma Shaodi , Sun Chenyu , Zhang Huimei , Qu Guangbo , Chen Yue , Cheng Ce , Chen Eric L. , Ahmed Mubashir Ayaz , Kim Keun Young , Manem Reveena , Chen Mengshi , Guo Zhichun , Yang Hongru , Yan Yue , Zhou Qin
Published: January 2021

Background

During the current Coronavirus Disease 2019 (COVID-19) pandemic, diabetic patients face disproportionately more. Anti-inflammatory effects of hypoglycemic agents have been reported, and their beneficial or harmful effects in patients with diabetes and COVID-19 remain controversial.

Purpose

This study was performed to clarify this association.

Data Sources

Relevant literature was searched on China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, Chinese periodical service platform VIP Database, Sinomed (China Biology Medicine, CBM), MedRxiv, PubMed, ScienceDirect, Web of Science, Ovid Databases (LWW), Springer Link, Wiley Online Library, Oxford Academic, Nature Press Group, Cochrane Library and BMJ Evidence-Based Medicine up to November 14, 2020.

Study Selection

Only observational studies of hypoglycemic agents vs. drugs or therapy without hypoglycemic agents in adult diabetic patients with COVID-19 were included.

Data Extraction

Data of death and poor composite outcomes were extracted.

Data Synthesis

The pooled effects were calculated using the fixed-effects or random-effects models based on heterogeneity assessment.

Limitation

Most studies were retrospective cohort studies with relative weak capability to verify causality.

Conclusion

Home use of metformin might be beneficial in decreasing mortality in diabetic patients infected with SARS-CoV-2. There is insufficient evidence to conclude that metformin and other hypoglycemic agents are associated with poor composite outcomes. More prospective studies, especially RCTs are needed.

Registration-PROSPERO

CRD42020221951.
Bolstering fitness via opportunistic CO2fixation: mixotroph dominance in modern groundwater
Authors: Taubert Martin , Overholt Will A. , Heinze Beatrix M. , Matanfack Georgette Azemtsop , Houhou Rola , Jehmlich Nico , von Bergen Martin , Rösch Petra , Popp Jürgen , Küsel Kirsten
Published: January 2021

The current understanding of organic carbon inputs into ecosystems lacking photosynthetic primary production is predicated on data and inferences derived almost entirely from metagenomic analyses. The elevated abundances of putative chemolithoautotrophs in groundwaters suggest that dark CO2fixation is an integral component of subsurface trophic webs. To understand the impact of autotrophically-fixed carbon, the flux of CO2-derived carbon through various subpopulations of subsurface microbiota must first be resolved, both quantitatively and temporally. Here, we implement novel stable isotope cluster analysis to render a time-resolved and quantitative evaluation of13CO-derived carbon flow through a groundwater microbiome stimulated with reduced sulfur compounds. We demonstrate that mixotrophs, not obligate chemolithoautotrophs, were the most abundant active organisms in groundwater microcosms. Species ofHydrogenophaga,Polaromonas,Dechloromonas, and other metabolically versatile mixotrophs drove the recycling of organic carbon and, when chance afforded, supplemented their carbon requirements via chemolithoautotrophy and uptake of available organic compounds. Mixotrophic activity facilitated the replacement of 43 and 80% of total microbial carbon stores with13C in just 21 and 70 days, respectively. This opportunistic “utilize whatever pathways net the greatest advantage in fitness” strategy may explain the great abundances of mixotrophs in other oligotrophic habitats, like the upper ocean and boreal lakes.
Determining significant correlation between pairs of extant characters in a small parsimony framework
Authors: Khandai Kaustubh , Navarro-Martinez Cristian , Smith Brendan , Buonopane Rebecca , Byun S. Ashley , Patterson Murray
Published: January 2021

When studying the evolutionary relationships among a set of species, the principle of parsimony states that a relationship involving the fewest number of evolutionary events is likely the correct one. Due to its simplicity, this principle was formalized in the context of computational evolutionary biology decades ago by,e.g., Fitch and Sankoff. Because the parsimony framework does not require a model of evolution, unlike maximum likelihood or Bayesian approaches, it is often a good starting point when no reasonable estimate of such a model is available.

In this work, we devise a method for determining if pairs of discrete characters are significantly correlated across all most parsimonious reconstructions, given a set of species on these characters, and an evolutionary tree. The first step of this method is to use Sankoff’s algorithm to computeallmost parsimonious assignments of ancestral states (of each character) to the internal nodes of the phylogeny. Correlation between a pair of evolutionary events (e.g., absent to present) for a pair of characters is then determined by the (co-) occurrence patterns between the sets of their respective ancestral assignments. The probability of obtaining a correlation this extreme (or more) under a null hypothesis where the events happen randomly on the evolutionary tree is then used to assess the significance of this correlation. We implement this method:parcours(PARsimonious CO-occURrenceS) and use it to identify significantly correlated evolution among vocalizations and morphological characters in the Felidae family.

Theparcourstool is freely available athttps://github.com/murraypatterson/parcours
Proteomic characterization of GSK3β knockout shows altered cell adhesion and metabolic pathway utilisation in colorectal cancer cells.
Authors: Bowler-Barnett E.H. , Martinez-Garcia F. D. , Sherwood M. , Weston S. , Wang Y. , Divecha N. , Skipp P. , Ewing R.M.
Published: January 2021

Glycogen-specific kinase (GSK3β) is an integral regulator of the Wnt signalling pathway as well as many other diverse signalling pathways and processes. Dys-regulation of GSK3β is implicated in many different pathologies, including neurodegenerative disorders as well as many different tumour types. In the context of tumour development, GSK3β has been shown to play both oncogenic and tumour suppressor roles, depending upon tissue, signalling environment or disease progression. Although multiple substrates of the GSK3β kinase have been identified, the wider protein networks within which GSK3β participates are not well known, and the consequences of these interactions not well understood. In this study, LC-MS/MS expression analysis was performed using knockout GSK3β colorectal cancer cells and isogenic controls in colorectal cancer cell lines carrying dominant stabilizing mutations of β-Catenin. Consistent with the role GSK3β, we found that β-Catenin levels and canonical Wnt activity are unaffected by knockout of GSK3β and therefore use this knockout cell model to identify other processes in which GSK3β is implicated. Quantitative proteomic analysis revealed perturbation of proteins involved in cell-cell adhesion, and we characterize the phenotype and altered proteomic profiles associated with this. We also characterize the perturbation of metabolic pathways resulting from GSK3β knockout and identify defects in glycogen metabolism. In summary, using a precision colorectal cancer cell-line knockout model with constitutively activated β-Catenin we are able to identify several of the diverse pathways and processes associated with GSK3β function.
Modulation of the spontaneous brain activity and functional connectivity in the triple resting-state networks following the visual oddball paradigm
Authors: Sbaihat Hasan , Rajkumar Ravichandran , Ramkiran Shukti , Assi Abed Al-Nasser , Shah N. Jon , Veselinović Tanja , Neuner Irene
Published: January 2021

The default mode network (DMN), the salience network (SN), and the central executive network (CEN) could be considered as the core resting-state brain networks (RSN) due to their involvement in a wide range of cognitive tasks. Despite the large body of knowledge relating to their regional spontaneous activity (RSA) and functional connectivity (FC) of these networks, less is known about the influence of task-associated activity on these parameters and on the interaction between these three networks. We have investigated the effects of the visual-oddball paradigm on three fMRI measures (amplitude of low-frequency fluctuations for RSA, regional homogeneity for local FC, and degree centrality for global FC) in these three core RSN networks. A rest-task-rest paradigm was used and the RSNs were identified using independent component analysis (ICA) on the resting-state data. We found that the task-related brain activity induced different patterns of significant changes within the three RS networks. Most changes were strongly associated with the task performance. Furthermore, the task-activity significantly increased the inter-network correlations between the SN and CEN as well as between the DMN and CEN, but not between the DMN and SN. A significant dynamical change in RSA, alongside local and global FC within the three core resting-state networks following a simple cognitive activity may be an expression of the distinct involvement of these networks in the performance of the task and their various outcomes.
The relationship between ageing and changes in the human blood and brain methylomes
Authors: Bryant Patrick , Elofsson Arne
Published: January 2021

Changes in DNA methylation have been found to be strongly correlated with age, enabling the creation of “epigenetic clocks”. Previously, studies on the relationship between ageing and DNA methylation have assumed a linear relationship, but no study has shown this always to be the case. We show that the relationships between significant methylation changes and ageing are different in different tissues, and that these changes show variable rates across life. Further, we observe a tendency for saturation as ageing proceeds. We provide a straightforward method of assessing all methylation-age relationships and cluster them according to their relative change rates based on fold change. Less than 13% of the significant markers selected here are used in the most common epigenetic clocks. When the significant markers display largely non-linear relationships, our fold change selection outperforms the most common epigenetic clocks in predicting age. We also show that the saturation observed at older ages explains the earlier observations that the epigenetic clock consistently underestimates the age in older samples. The findings imply that markers selected from linear adjustments or correlations do not represent the most meaningful biological changes.
Youthful and age-related matreotypes predict drugs promoting longevity
Authors: Statzer Cyril , Jongsma Elisabeth , Liu Sean X. , Dakhovnik Alexander , Wandrey Franziska , Mozharovskyi Pavlo , Zülli Fred , Ewald Collin Y.
Published: January 2021

The identification and validation of drugs that promote health during aging (‘geroprotectors’) is key to the retardation or prevention of chronic age-related diseases. Here we found that most of the established pro-longevity compounds shown to extend lifespan in model organisms also alter extracellular matrix gene expression (i.e.,matrisome) in human cell lines. To harness this novel observation, we used age-stratified human transcriptomes to define the age-related matreotype, which represents the matrisome gene expression pattern associated with age. Using a ‘youthful’ matreotype, we screenedin silicofor geroprotective drug candidates. To validate drug candidates, we developed a novel tool using prolonged collagen expression as a non-invasive andin-vivosurrogate marker forC. eleganslongevity. With this reporter, we were able to eliminate false positive drug candidates and determine the appropriate dose for extending the lifespan ofC. elegans. We improved drug uptake for one of our predicted compounds, genistein, and reconciled previous contradictory reports of its effects on longevity. We identified and validated new compounds, tretinoin, chondroitin sulfate, and hyaluronic acid, for their ability to restore age-related decline of collagen homeostasis and increase lifespan. Thus, our innovative drug screening approach - employing extracellular matrix homeostasis - facilitates the discovery of pharmacological interventions promoting healthy aging.

Highlights

Many geroprotective drugs alter extracellular matrix gene expression

Defined young and old human matreotype signatures can identify novel potential geroprotective compounds

Prolonged collagen homeostasis as a surrogate marker for longevity
Local protein synthesis of mtIF3 regulates mitochondrial translation for axonal development
Authors: Lee Soyeon , Park Dongkeun , Lim Chunghun , Kim Jae-Ick , Min Kyung-Tai
Published: January 2021

Mitochondrial initiation factor 3 (mtIF3) binds to and dissociates mitochondrial ribosomes. The mtIF3-small subunit complex then recruits mtIF2, mRNA, and N-formylmethionine-tRNA to initiate mitochondrial translation. Intriguingly, transcripts of the nuclear-encoded mtIF3 gene have been shown present in axonal growth cones; however, the biological function of this compartmentalization remains largely unknown. Here, we demonstrate that brain-derived neurotrophic factor (BDNF) induces local translation of mtIF3 mRNA in axonal growth cones. Subsequently, mtIF3 protein is translocated into axonal mitochondria and promotes mitochondrial translation as assessed by our newly developed bimolecular fluorescence complementation sensor for the assembly of mitochondrial ribosomes. We further show that BDNF-induced axonal growth requires mtIF3-dependent mitochondrial translation in axons. These findings provide new insight into how neurons adaptively control mitochondrial physiology and axonal development via local mtIF3 translation.
Note: Updating the metadata of four misidentified samples in the DrosRTEC dataset
Authors: Nunez Joaquin C. B. , Paris Margot , Machado Heather , Bogaerts Maria , Gonzalez Josefa , Flatt Thomas , Coronado Marta , Kapun Martin , Schmidt Paul , Petrov Dmitri , Bergland Alan
Published: January 2021

This note details the consortium’s rationale behind its decision to modify the metadata for putatively misidentified European samples in the DrosRTEC dataset. In brief, we use PCA on published datasets from North America and Europe to generate phylogeographic clusters reflective of worldwideD. melanogasterdemography. We used this PCA to train a DAPC model in order the predict the group membership. Our results indicate that 4 out of 73 samples were misclassified and the metadata was updated accordingly. These samples are a spring-fall pair from Spain and Austria.