bluuebunny/crossref_metadata_2025_split huggingface dataset:
Universal protein misfolding intermediates can bypass the proteostasis network and remain soluble and less functional
Authors: Nissley Daniel , Jiang Yang , Trovato Fabio , Sitarik Ian , Narayan Karthik , To Philip , Xia Yingzi , Fried Stephen D. , O’Brien Edward P. 
Published: August 2021

ABSTRACTMisfolded protein conformations with decreased functionality can bypass the proteostasis machinery and remain soluble in vivo. This is an unexpected phenomenon as several cellular quality control mechanisms have evolved to rid cells of misfolded proteins. Three questions, then, are: how is it structurally possible for long-lived, soluble, misfolded proteins to bypass the proteostasis machinery and processes? How widespread are these soluble, misfolded states across the proteome? And how long do they persist for? Here, we address these questions using coarse-grain molecular dynamics simulations of the synthesis, termination, and post-translational dynamics of a representative set of cytosolic E. coli proteins. We predict that half of all proteins exhibit subpopulations of misfolded conformations that are likely to bypass molecular chaperones, avoid aggregation, and not be rapidly degraded. These misfolded states may persist for months or longer for some proteins. Structurally characterizing these misfolded states, we observe they have a large amount of native structure, but also contain localized misfolded regions from non-native changes in entanglement, in which a protein segment threads through a loop formed by another portion of the protein that is not found in the native state. The surface properties of these misfolded states are native like, suggesting they may bypass the proteostasis machinery and its regulatory processes to remain soluble, while their entanglements make these states long-lived kinetic traps, as disentanglement requires unfolding of already folded portions of the protein. In terms of function, we predict that one-third of proteins have subpopulations that misfold into less-functional states that have structurally perturbed functional sites yet remain soluble. Data from limited-proteolysis mass spectrometry experiments, which interrogate the misfolded conformations populated by proteins upon unfolding and refolding, are consistent with the structural changes seen in the entangled states of glycerol-3-phosphate dehydrogenase upon misfolding. These results provide an explanation for how proteins can misfold into soluble conformations with reduced functionality that can bypass cellular quality controls, and indicate, unexpectedly, this may be a wide-spread phenomenon in proteomes. Such entanglements are observed in many native structures, suggesting the non-native entanglements we observe are plausible. More broadly, these near-native entangled structures suggest a hypothesis for how synonymous mutations can modulate downstream protein structure and function, with these mutations partitioning nascent proteins between these kinetically trapped states.
Range-wide habitat use and Key Biodiversity Area coverage for a lowland tropical forest raptor across an increasingly deforested landscape
Authors: Sutton Luke J. , Anderson David L. , Franco Miguel , McClure Christopher J.W. , Miranda Everton B.P. , Vargas F. Hernán , Vargas González José de J. , Puschendorf Robert 
Published: August 2021

AbstractQuantifying habitat use is important for understanding how animals meet their requirements for survival and provides useful information for conservation planning. Currently, assessments of range-wide habitat use that delimit species distributions are incomplete for many taxa. The harpy eagle (Harpia harpyja) is a raptor of conservation concern, widely distributed across Neotropical lowland forests, that currently faces threats from increasing habitat loss and fragmentation. Here, we use a logistic regression modelling framework to identify habitat resource selection and predict habitat suitability based on a new method developed from the International Union for the Conservation of Nature Area of Habitat range metric. From the habitat use model, we performed a gap analysis to identify areas of high habitat suitability in regions with limited coverage in the Key Biodiversity Area (KBA) network. Range-wide habitat use indicated that harpy eagles prefer areas of 70-75 % evergreen forest cover, low elevation, and high vegetation heterogeneity. Conversely, harpy eagles avoid areas of >10 % cultivated landcover and mosaic forest, and topographically complex areas. Our habitat use model identified a large continuous area across the pan-Amazonia region, and a habitat corridor from the Chocó-Darién ecoregion of Colombia running north along the Caribbean coast of Central America. Little habitat was predicted across the Atlantic Forest biome, which is now severely degraded. The current KBA network covered ∼18 % of medium to high suitability harpy eagle habitat exceeding the target representation (10 %). Four major areas of high suitability habitat lacking coverage in the KBA network were identified in the Chocó-Darién ecoregion of Colombia, western Guyana, and north-west Brazil. We recommend these multiple gaps of habitat as new KBAs for strengthening the current KBA network. Modelled area of habitat estimates as described here are a useful tool for large-scale conservation planning and can be readily applied to many taxa.
Rapid radiation of Southern Ocean shags in response to receding sea ice
Authors: Rawlence Nicolas J. , Salis Alexander T. , Spencer Hamish G. , Waters Jonathan M. , Scarsbrook Lachie , Phillips Richard A. , Calderón Luciano , Cook Timothée R. , Bost Charles-André , Dutoit Ludovic , King Tania M. , Masello Juan F. , Nupen Lisa J. , Quillfeldt Petra , Ratcliffe Norman , Ryan Peter G. , Till Charlotte E. , Kennedy Martyn 
Published: August 2021

ABSTRACTAimUnderstanding how wild populations respond to climatic shifts is a fundamental goal of biological research in a fast-changing world. The Southern Ocean represents a fascinating system for assessing large-scale climate-driven biological change, as it contains extremely isolated island groups within a predominantly westerly, circumpolar wind and current system. The blue-eyed shags (Leucocarbospp.) represent a paradoxical Southern Ocean seabird radiation; a circumpolar distribution implies strong dispersal capacity yet their speciose nature suggests local adaptation and isolation. Here we use genetic tools in an attempt to resolve this paradox.LocationSouthern Ocean.Taxa17 species and subspecies of blue-eyed shags (Leucocarbospp.) across the geographical distribution of the genus.MethodsHere we use mitochondrial and nuclear sequence data to conduct the first global genetic analysis of this group using a temporal phylogenetic framework to test for rapid speciation.ResultsOur analysis reveals remarkably shallow evolutionary histories among island-endemic lineages, consistent with a recent high-latitude circumpolar radiation. This rapid sub-Antarctic expansion contrasts with significantly deeper lineages detected in more temperate regions such as South America and New Zealand that may have acted as glacial refugia. The dynamic history of high-latitude expansions is further supported by ancestral demographic and biogeographic reconstructions.Main conclusionsThe circumpolar distribution of blue-eyed shags, and their highly dynamic evolutionary history, potentially makeLeucocarboa strong sentinel of past and ongoing Southern Ocean ecosystem change given their sensitivity to climatic impacts.
Functional cortical localization of the tongue using corticokinematic coherence with a deep learning-assisted motion capture system
Authors: Maezawa Hitoshi , Fujimoto Momoka , Hata Yutaka , Matsuhashi Masao , Hashimoto Hiroaki , Kashioka Hideki , Yanagida Toshio , Hirata Masayuki 
Published: August 2021

AbstractMeasuring the corticokinematic coherence (CKC) between magnetoencephalographic and movement signals using an accelerometer can evaluate the functional localization of the primary sensorimotor cortex (SM1) of the upper limbs. However, it is difficult to determine the tongue CKC because an accelerometer yields excessive magnetic artifacts. We introduce and validate a novel approach for measuring the tongue CKC using a deep learning-assisted motion capture system with videography, and compare it with an accelerometer in a control task measuring finger movement. Twelve healthy volunteers performed rhythmical side-to-side tongue movements in the whole-head magnetoencephalographic system, which were simultaneously recorded using a video camera and examined offline using a deep learning-assisted motion capture system. In the control task, right finger CKC measurements were simultaneously evaluated via motion capture and an accelerometer. The right finger CKC with motion capture was significant at the movement frequency peaks or its harmonics over the contralateral hemisphere; the motion-captured CKC was 84.9% similar to that with the accelerometer. The tongue CKC was significant at the movement frequency peaks or its harmonics over both hemispheres, with no difference between the left and right hemispheres. The CKC sources of the tongue were considerably lateral and inferior to those of the finger. Thus, the CKC based on deep learning-assisted motion capture can evaluate the functional localization of the tongue SM1. In this approach, because no devices are placed on the tongue, magnetic noise, disturbances due to tongue movements, risk of aspiration of the device, and risk of infection to the experimenter are eliminated.
Mutualists construct the ecological conditions that trigger the transition from parasitism
Authors: Ledru Leo , Garnier Jimmy , Rhor Matthias , Nous Camille , Ibanez Sebastien 
Published: August 2021

AbstractThe evolution of mutualism between hosts and initially parasitic symbionts represents a major transition in evolution. Although vertical transmission of symbionts during host reproduction and partner control both favour the stability of mutualism, these mechanisms require specifically evolved features that may be absent in the first place. Therefore, the first steps of the transition from parasitism to mutualism may suffer from the cost of mutualism at the organismic level. We hypothesize that spatial structure can lead to the formation of higher selection levels favouring mutualism. This resembles the evolution of altruism, with the additional requirement that the offspring of mutualistic hosts and symbionts must co-occur often enough. Using a spatially explicit agent-based model we demonstrate that, starting from a parasitic system with global dispersal, the joint evolution of mutualistic effort and local dispersal of hosts and symbionts leads to a stable coexistence between parasites and mutualists. The evolution of local dispersal mimics vertical transmission and triggers the formation of mutualistic clusters, counteracting the organismic selection level of parasites that maintain global dispersal. The transition occurs when mutualistic symbionts increase the density of hosts, which strengthens competition between hosts and disfavours hosts inhabiting areas dominated by parasitic symbionts: mutualists construct the ecological conditions that allow their own spread. Therefore, the transition to mutualism may come from an eco-evolutionary feedback loop involving spatially structured population dynamics.
Geometric Deep Learning of the Human Connectome Project Multimodal Cortical Parcellation
Authors: Williams Logan Z. J. , Fawaz Abdulah , Glasser Matthew F. , David Edwards A. , Robinson Emma C. 
Published: August 2021

AbstractUnderstanding the topographic heterogeneity of cortical organisation is an essential step towards precision modelling of neuropsychiatric disorders. While many cortical parcellation schemes have been proposed, few attempt to model inter-subject variability. For those that do, most have been proposed for high-resolution research quality data, without exploration of how well they generalise to clinical quality scans. In this paper, we benchmark and ensemble four different geometric deep learning models on the task of learning the Human Connectome Project (HCP) multimodal cortical parcellation. We employ Monte Carlo dropout to investigate model uncertainty with a view to propagate these labels to new datasets. Models achieved an overall Dice overlap ratio of >0.85 ± 0.02. Regions with the highest mean and lowest variance included V1 and areas within the parietal lobe, and regions with the lowest mean and highest variance included areas within the medial frontal lobe, lateral occipital pole and insula. Qualitatively, our results suggest that more work is needed before geometric deep learning methods are capable of fully capturing atypical cortical topographies such as those seen in area 55b. However, information about topographic variability between participants was encoded in vertex-wise uncertainty maps, suggesting a potential avenue for projection of this multimodal parcellation to new datasets with limited functional MRI, such as the UK Biobank.
ATP hydrolysis tunes specificity of a AAA+ protease
Authors: Mahmoud Samar A. , Aldikacti Berent , Chien Peter 
Published: August 2021

SummaryIn bacteria, AAA+ proteases such as Lon and ClpXP degrade substrates with exquisite specificity. These machines capture the energy of ATP hydrolysis to power unfolding and degradation of target substrates. Here, we show that a mutation in the ATP binding site of ClpX shifts protease specificity to promote degradation of normally Lon-restricted substrates. However, this ClpX mutant is worse at degrading ClpXP targets, suggesting an optimal balance in substrate preference for a given protease that is surprisingly easy to alter. In vitro, wildtype ClpXP also degrades Lon-restricted substrates more readily when ATP levels are reduced, similar to the shifted specificity of mutant ClpXP, which has altered ATP hydrolysis kinetics. Based on these results, we suggest that rates of ATP hydrolysis not only power substrate unfolding and degradation, but also tune protease specificity. We consider various models for this effect based on emerging structures of AAA+ machines showing conformationally distinct states.Abstract FigureGraphical AbstracteTOCAAA+ proteases, such as Lon and ClpXP, select distinct targets for degradation to maintain proteostasis. Mahmoud et al. show that ATP hydrolysis can tune substrate specificity of ClpX, allowing ClpX to degrade Lon-restricted substrates under limiting ATP conditions or in the presence of a ClpX mutant.HighlightsA Walker B mutation of the AAA+ protease ClpX alters substrate specificityClpX mutant degrades new substrates but degrades canonical substrates less wellDecreasing ATP levels enhances ClpXP mediated degradation of some classes of substratesATP-induced changes in conformational states accompany alterations in ClpX specificity
Genetic Analysis of Bphse: a Novel Gene Complementing Resistance to Bordetella pertussis-Induced Histamine Sensitization
Authors: Raza Abbas , Diehl Sean A. , Case Laure K. , Krementsov Dimitry N. , Li Dawei , Kost Jason , Ball Robyn L. , Chesler Elissa J. , Philip Vivek M. , Huang Rui , Chen Yan , Ma Runlin , Tyler Anna L. , Mahoney J. Mathew , Blankenhorn Elizabeth P. , Teuscher Cory 
Published: August 2021

AbstractHistamine is a bioactive amine associated with a plethora of normal and pathophysiological processes, with the latter being dependent on both genetic and environmental factors including infectious agents. Previously, we showed in mice that susceptibility to Bordetella pertussis and pertussis toxin (PTX) induced histamine sensitization (Bphs) is controlled by histamine receptor H1 (Hrh1/HRH1) alleles. Bphs susceptible and resistant alleles (Bphss/Bphsr) encode for two-conserved protein haplotypes. Given the importance of HRH1 signaling in health and disease, we sequenced Hrh1 across an extended panel of laboratory and wild-derived inbred strains and phenotyped them for Bphs. Unexpectedly, eight strains homozygous for the Bphsr allele phenotyped as Bphss, suggesting the existence of a modifying locus segregating among the strains capable of complementing Bphsr. Genetic analyses mapped this modifier locus to mouse chromosome 6; designated Bphs-enhancer (Bphse), within a functional linkage disequilibrium domain encoding multiple loci controlling responsiveness to histamine (Bphs/Hrh1 and Histh1-4). Interval-specific single-nucleotide polymorphism (SNP) based association testing across 50 laboratory and wild-derived inbred mouse strains and functional prioritization analyses resulted in the identification of candidate genes for Bphse within a ∼5.5 Mb interval (Chr6:111.0-116.4 Mb), including Atg7, Plxnd1, Tmcc1, Mkrn2, Il17re, Pparg, Lhfpl4, Vgll4, Rho and Syn2. Taken together, these results demonstrate the power of combining network-based computational methods with the evolutionarily significant diversity of wild-derived inbred mice to identify novel genetic mechanisms controlling susceptibility and resistance to histamine shock.
Interior of sand fly (Diptera: Psychodidae) abdomen reveals novel structures involved in pheromone release: discovering the Manifold
Authors: Tonelli G.B. , Andrade-Filho J.D. , Campos A.M. , Margonari C. , Amaral A.R. , Volf P. , Shaw E. , Hamilton J.G.C. 
Published: August 2021

AbstractThe males of many species of New World Phlebotomines produce volatile terpenoid chemicals which have been shown in Lutzomyia longipalpis s.l. and L. cruciata to be sex/aggregation pheromones which attract female and male conspecifics. Pheromone is produced in secretory cells surrounding a cuticular reservoir which collects the pheromone and passes it through a cuticular duct to the surface of the insect. On the surface the pheromone passes through a specialised structure prior to evaporation. The shape and distribution of the structures are highly diverse and differ according to species. They range in appearance from slightly raised domes (papules) to almost spherical apple shaped structures to slight depressions with central spikes and all with a central pore. They can occur either singly or in many hundreds distributed on most abdominal tergites or grouped on one. The pheromone secreting apparatus in sand flies and other insects have historically been examined from the exterior using scanning electron microscopy (SEM) and from the interior using transmission electron microscopy. In this study we used SEM to examine the interior cuticular structure of 3 members of the Lutzomyia longipalpis s.l. species complex and Migonemyia migonei and found a new structure associated with pheromone release which we have called the Manifold. The Manifold is a substantial structure siting in-line between the cuticular duct and the underside of the tergite. Differences in the size and shape of the Manifold may be related to the chemical structure of the pheromone. In addition to the importance of this hitherto unknown structure in the production, dissemination and ecology of the pheromone, as well as its potential taxonomic value, examination of the interior cuticle by SEM may help locate the secretory apparatus in important vector species where pheromonal activity has been inferred from behavioural studies but the external secretory structures or potential pheromones have not been found.
Dissociable plasticity of the nucleus basalis of Meynert in early and late blind individuals
Authors: Bang Ji Won , Chan Russell W. , Parra Carlos , Murphy Matthew C. , Schuman Joel S. , Nau Amy C. , Chan Kevin C. 
Published: August 2021

AbstractPlasticity in the brain is differentially affected by age of blindness onset. One possible, but not yet identified mechanism is that the cholinergic signals originating from the nucleus basalis of Meynert may underlie differential extent of plasticity in early and late blind individuals. This prospect is based on the fact that the nucleus basalis of Meynert modulates cortical processes such as plasticity and sensory encoding and that the degree of cross-modal plasticity varies depending on the age of blindness onset. However, this question yet remains largely unclear. Here, we tested whether the early and late blind individuals develop dissociable plasticity in the nucleus basalis of Meynert using multi-parametric magnetic resonance imaging. We found the relatively preserved volumetric size and cerebrovascular reactivity, but significant disruption in the white matter integrity of the nucleus basalis of Meynert in both early and late blind individuals. Critically, despite its reduction in the white matter integrity, the nucleus basalis of Meynert of early blind individuals presented greater global and network functional connectivity including visual, language, and default-mode networks. Such changes in the functional connectivity were not observed in the late-blind individuals. Further, less duration of the visual experience was associated with greater global and network functional connectivity. These results indicate that the nucleus basalis of Meynert is differentially involved in the plasticity of early and late blind individuals – a similar amount of reduction in microstructural integrity in early and late blind individuals, but stronger and more widespread functional connectivity of the NBM in the early blind individuals. Our findings suggest that the nucleus basalis of Meynert may develop greater cholinergic influence on the cortex of early blind individuals. Such change may explain why early blind individuals present stronger and more widespread cross-modal plasticity during non-visual tasks compared to late blind individuals.
The PAF1 complex cell-autonomously promotes oogenesis in Caenorhabditis elegans
Authors: Kubota Yukihiro , Ota Natsumi , Takatsuka Hisashi , Unno Takuma , Onami Shuichi , Sugimoto Asako , Ito Masahiro 
Published: August 2021

AbstractThe RNA polymerase II-associated factor 1 complex (PAF1C) is a protein complex that consists of LEO1, RTF1, PAF1, CDC73, and CTR9, and has been shown to be involved in Pol II-mediated transcriptional and chromatin regulation. Although it has been shown to regulate a variety of biological processes, the precise role of the PAF1C during germ line development has not been clarified. In this study, we found that reduction in the function of the PAF1C components, LEO-1, RTFO-1, PAFO-1, CDC-73, and CTR-9, in Caenorhabditis elegans affects cell volume expansion of oocytes. Defects in oogenesis were also confirmed using an oocyte maturation marker, OMA-1::GFP. While four to five OMA-1::GFP-positive oocytes were observed in wild-type animals, their numbers were significantly decreased in pafo-1 mutant and leo-1(RNAi), cdc-73(RNAi), and pafo-1(RNAi) animals. Expression of a functional PAFO-1::mCherry transgene in the germline significantly rescued the oogenesis-defective phenotype of the pafo-1 mutants, suggesting that expression of the PAF1C in germ cells is required for oogenesis. Notably, overexpression of OMA-1::GFP partially rescued the oogenesis defect in the pafo-1 mutants. Based on our findings, we propose that the PAF1C promotes oogenesis in a cell-autonomous manner by positively regulating the expression of genes involved in oocyte maturation.