bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proximity-labeling chemoproteomics defines the subcellular cysteinome and inflammation-responsive mitochondrial redoxome
Authors: Yan Tianyang , Julio Ashley R. , Villanueva Miranda , Jones Anthony E. , Ball Andréa B. , Boatner Lisa M. , Turmon Alexandra C. , Yen Stephanie L. , Desai Heta S. , Divakaruni Ajit S. , Backus Keriann M. 
Published: January 2023

AbstractProteinaceous cysteines function as essential sensors of cellular redox state. Consequently, defining the cysteine redoxome is a key challenge for functional proteomic studies. While proteome-wide inventories of cysteine oxidation state are readily achieved using established, widely adopted proteomic methods such as OxiCat, Biotin Switch, and SP3-Rox, they typically assay bulk proteomes and therefore fail to capture protein localization-dependent oxidative modifications. To obviate requirements for laborious biochemical fractionation, here, we develop and apply an unprecedented two step cysteine capture method to establish the Local Cysteine Capture (Cys-LoC), and Local Cysteine Oxidation (Cys-LOx) methods, which together yield compartment-specific cysteine capture and quantitation of cysteine oxidation state. Benchmarking of the Cys-LoC method across a panel of subcellular compartments revealed more than 3,500 cysteines not previously captured by whole cell proteomic analysis. Application of the Cys-LOx method to LPS stimulated murine immortalized bone marrow-derived macrophages (iBMDM), revealed previously unidentified mitochondria-specific inflammation-induced cysteine oxidative modifications including those associated with oxidative phosphorylation. These findings shed light on post-translational mechanisms regulating mitochondrial function during the cellular innate immune response.
Intracellular conformation of amyotrophic lateral sclerosis-causative TDP-43
Authors: Kitamura Akira , Yuno Sachiko , Kawamura Rintaro , Kinjo Masataka 
Published: January 2023

AbstractTransactive response element DNA/RNA-binding protein 43 kDa (TDP-43) is the causative protein of amyotrophic lateral sclerosis (ALS); several ALS-associated mutants of TDP-43 have been identified. TDP-43 has several domains: an N-terminal domain, two RNA/DNA-recognition motifs, and a C-terminal intrinsically disordered region (IDR). Its structures have been partially determined, but the whole structure remains elusive. In this study, we investigate the possible end-to-end distance between the N- and C-termini of TDP-43, its alterations due to ALS-associated mutations in the IDR, and its apparent molecular shape in live cells using Förster resonance energy transfer (FRET) and fluorescence correlation spectroscopy (FCS). Further-more, the interaction between ALS-associated TDP-43 and heteronuclear ribonucleoprotein A1 (hnRNP A1) is slightly stronger than that of wild-type TDP-43. Our findings provide insights into the structure of wild-type and ALS-associated mutants of TDP-43 in a cell.
Loss of FAM111B protease mutated in hereditary fibrosing poikiloderma syndrome negatively regulates telomere length
Authors: Kliszczak Maciej , Moralli Daniela , Jankowska Julia D. , Bryjka Paulina , Meem Lamia Subha , Goncalves Tomas , Hester Svenja S. , Fisher Roman , Clynes David , Green Catherine M. 
Published: January 2023

AbstractHereditary fibrosing poikiloderma (HFP) is a rare human dominant negative disorder caused by mutations in theFAM111Bgene that encodes a nuclear trypsin-like serine protease. HFP patients present with symptoms including skin abnormalities, tendon contractures, myopathy and lung fibrosis. We characterised the cellular roles of human FAM111B using U2OS and MCF7 cell lines and report here that the protease interacts with components of the nuclear pore complex. Loss ofFAM111Bexpression resulted in abnormal nuclear shape and reduced telomeric DNA content suggesting that FAM111B protease is required for normal telomere length; we show that this function is independent of telomerase or recombination driven telomere extension. Even thoughFAM111B-deficient cells were proficient in DNA repair, they showed hallmarks of genomic instability such as increased levels of micronuclei and ultra-fine DNA bridges. Interestingly, FAM111B variants, including mutations that cause HFP, showed more frequent localisation to the nuclear lamina suggesting that accumulation of mutant FAM111B at the nuclear periphery may drive the disease pathology.
Two residues determine nicotinic acetylcholine receptor requirement for RIC-3
Authors: Noonan Jennifer D. , Beech Robin N. 
Published: January 2023

AbstractNicotinic acetylcholine receptors (N-AChRs) mediate fast synaptic signalling and are members of the pentameric ligand-gated ion channel (pLGIC) family. They rely on a network of accessory proteinsin vivofor correct formation and transport to the cell surface. RIC-3 is an endoplasmic reticulum protein that physically interacts with nascent pLGIC subunits and promotes their oligomerization. It is not known why some N-AChRs require RIC-3 in heterologous expression systems, while others do not. Previously we reported that the ACR-16 N-AChR from the parasitic nematodeDracunculus medinensisdoes not require RIC-3 inXenopus laevisoocytes. This is unusual because all other nematode ACR-16, like the closely relatedAscaris suumACR-16, require RIC-3. Their high sequence similarity limits the number of amino acids that may be responsible, and the goal of this study was to identify them. A series of chimeras and point mutations betweenA. suum and D. medinensisACR-16, followed by functional characterization with electrophysiology, identified two residues that account for a majority of the receptor requirement for RIC-3. ACR-16 with R/K159 in the cys-loop and I504 in the C-terminal tail did not require RIC-3 for functional expression. Mutating either of these to R/K159E or I504T, residues found in other nematode ACR-16, conferred a RIC-3 requirement. Our results agree with previous studies showing that these regions interact and are involved in receptor synthesis. Although it is currently unclear what precise mechanism they regulate, these residues may be critical during specific subunit folding and/or assembly cascades that RIC-3 may promote.
Mental image reconstruction from human brain activity
Authors: Koide-Majima Naoko , Nishimoto Shinji , Majima Kei 
Published: January 2023

AbstractVisual images perceived by humans can be reconstructed from their brain activity. However, the visualization (externalization) of mental imagery remains a challenge. In this study, we demonstrated that the visual image reconstruction method proposed in the seminal study by Shen et al. (2019) heavily relied on low-level visual information decoded from the brain and could not efficiently utilize semantic information that would be recruited during mental imagery. To address this limitation, we extended the previous method to a Bayesian estimation framework and introduced the assistance of semantic information into it. Our proposed framework successfully reconstructed both seen (i.e., directly captured by the human eye) and imagined images from the brain activity. These results suggest that our framework would provide a technology for directly investigating the subjective contents of the brain.
Androgen aggravates aortic aneurysms via suppressing PD-1 in mice
Authors: Mu Xufang , Liu Shu , Wang Zhuoran , Jiang Kai , McClintock Tim , Stromberg Arnold J. , Tezanos Alejandro V. , Lee Eugene S , Curci John A. , Gong Ming C , Guo Zhenheng 
Published: January 2023

AbstractAndrogen has long been recognized for its pivotal role in the sexual dimorphism of cardiovascular diseases, including aortic aneurysms, a devastating vascular disease with a higher prevalence and mortality rate in men than women. However, the molecular mechanism by which androgen mediates aortic aneurysms is largely unknown. Here, we report that male but not female mice develop aortic aneurysms in response to aldosterone and high salt (Aldo-salt). We demonstrate that both androgen and androgen receptors (AR) are crucial for the sexually dimorphic response to Aldo-salt. We identify T cells expressing programmed cell death protein 1 (PD-1), an immune checkpoint molecule important in immunity and cancer immunotherapy, as a key link between androgen and aortic aneurysms. We show that intraperitoneal injection of anti-PD-1 antibody reinstates Aldo-salt-induced aortic aneurysms in orchiectomized mice. Mechanistically, we demonstrate that AR binds to the PD-1 promoter to suppress its expression in the spleen. Hence, our study reveals an important but unexplored mechanism by which androgen contributes to aortic aneurysms by suppressing PD-1 expression in T cells. Our study also suggests that cancer patients predisposed to the risk factors of aortic aneurysms may be advised to screen for aortic aneurysms during immune checkpoint therapy.Graphical Abstract
Evolutionarily diverse fungal zoospores show contrasting swimming patterns specific to ultrastructure
Authors: Galindo Luis Javier , Richards Thomas A. , Nirody Jasmine A. 
Published: January 2023

SummaryZoosporic fungi, also called chytrids, produce motile spores with flagellar swimming tails (zoospores)1,2. These fungi are key components of aquatic food webs, acting as pathogens, saprotrophs and prey3–8. Little is known about the swimming behaviour of fungal zoospores, a crucial factor governing dispersal, biogeographical range, ecological function and infection dynamics6,9. Here, we track the swimming patterns of zoospores from 12 evolutionary divergent species of zoosporic fungi across seven orders of the Chytridiomycota and the Blastocladiomycota phyla. We report two major swimming patterns which correlate with the cytoskeletal ultrastructure of these zoospores. Specifically, we show that species without major cytoplasmic tubulin components swim in a circular fashion, while species that harbour prominent cytoplasmic tubulin structures swim in a pattern akin to a random walk (move-stop-redirect-move). We confirm cytoskeleton architecture by performing fluorescence confocal microscopy of the zoospores across all 12 species. We then treat representative species with variant swimming behaviours and cytoplasmic-cytoskeletal arrangements with tubulin stabilizing (Taxol) and depolymerizing (Nocodazole) pharmacological-compounds. We observed that when treating the ‘random-walk’ species with Nocodazole their swimming behaviour changes to a circular swimming pattern. Confocal imaging of the nocodazole-treated zoospores demonstrates these cells maintain flagellum tubulin structures but lack their characteristic cytoplasmatic tubulin arrangement. These data confirm that the capability of zoospores to perform ‘complex’ movements as a random walk is linked to the presence of prominent cytoplasmatic tubulin structures. We discuss the link between cytology, sensation, and swimming behaviour manifest in zoosporic fungi.
Site-specific structure and stability constrained substitution models improve phylogenetic inference
Authors: Lorca-Alonso Ivan , Arenas Miguel , Bastolla Ugo 
Published: January 2023

AbstractIn previous studies, we presented site-specific substitution models of protein evolution based on selection on the folding stability of the native state (Stab-CPE), which predict more realistically the evolutionary variability across protein sites. However, those Stab-CPE present qualitative differences from observed data, probably because they ignore changes in the native structure, despite empirical studies suggesting that conservation of the native structure is a stronger selective force than selection on folding stability.Here we present novel structurally constrained substitution models (Str-CPE) based on Julián Echave’s model of the structural change due to a mutation as the linear response of the protein to a perturbation and on the explicit model of the perturbation generated by a specific amino-acid mutation. Compared to our previous Stab-CPE models, the novel Str-CPE models are more stringent (they predict lower sequence entropy and substitution rate), provide higher likelihood to multiple sequence alignments (MSA) that include one or more known structures, and better predict the observed conservation across sites. The models that combine Str-CPE and Stab-CPE models are even more stringent and fit the empirical MSAs better. We refer collectively to our models as structure and stability constrained substitution models (SSCPE). Importantly in comparison to the traditional empirical substitution models, the SSCPE models infer phylogenetic trees of distantly related proteins more similar to reference trees based on structural information. We implemented the SSCPE models in the program SSCPE.pl, freely available athttps://github.com/ugobas/SSCPE, which infers phylogenetic trees under the SS-CPE models with the program RAxML-NG from a concatenated alignment and a list of protein structures that overlap with it.
PC_sim: An integrated measure of protein sequence and structure similarity for improved alignments and evolutionary inference
Authors: Piette Oscar , Abia David , Bastolla Ugo 
Published: January 2023

AbstractMotivationEvolutionary inferences depend crucially on the quality of multiple sequence alignments (MSA), which is problematic for distantly related proteins. Since protein structure is more conserved than protein sequence, it seems natural to use structure alignments for distant homologs. However, structure alignments may not be suitable for inferring evolutionary relationships at the sequence level.ResultsHere we investigate the mutual relationships between four protein similarity measures that depend on sequence and structure (fraction of aligned residues, sequence similarity, fraction of superimposed backbones and contact overlap) and the corresponding alignments. Changes in protein sequences and structures are intimately correlated, but our results suggest that no individual measure can provide a complete and unbiased picture of changes in protein sequences and structure. Therefore, we propose a new hybrid measure of protein sequence and structure similarity based on Principal Components (PC_sim). Starting from an MSA, we obtain modified pairwise alignments (PA) based on PC_sim, and from them we construct a new MSA based on the maximal cliques of the PA graph. These alignments yield larger protein similarities and agree better with the Balibase “reference” MSA and with consensus MSA than alignments that target individual similarity measures. Moreover, PC_sim is associated with a divergence measure that correlates strongest with divergences obtained from individual similarities, which suggests that it can infer more accurate evolutionary divergences for the reconstruction of phylogenetic trees with distance methods.Availabilityhttps://github.com/ugobas/Evol_divContactubastolla@cbm.csic.es
Selective sweeps identification in distinct groups of cultivated rye (Secale cerealeL.) germplasm provides potential candidates for crop improvement
Authors: Hawliczek Anna , Borzęcka Ewa , Tofil Katarzyna , Alachiotis Nikolaos , Bolibok Leszek , Gawroński Piotr , Siekmann Dörthe , Hackauf Bernd , Dušinský Roman , Švec Miroslav , Bolibok-Brągoszewska Hanna 
Published: January 2023

AbstractBackgroundDuring domestication and subsequent improvement plants were subjected to intensive positive selection for desirable traits. Identification of selection targets is important with respect to the future targeted broadening of diversity in breeding programmes. Rye (Secale cerealeL.) is a cereal that is closely related to wheat, and it is an important crop in Central, Eastern and Northern Europe. The aim of the study was (i) to identify diverse groups of rye accessions based on high-density, genome-wide analysis of genetic diversity within a set of 478 rye accessions, covering a full spectrum of diversity within the genus, from wild accession to inbred lines used in hybrid breeding, and (ii) to identify selective sweeps in the established groups of cultivated rye germplasm and putative candidate genes targeted by selection.ResultsPopulation structure and genetic diversity analyses based on high-quality SNP (DArTseq) markers revealed the presence of three complexes in theSecalegenus:S. sylvestre, S. strictumandS. cereale/vavilovii, a relatively narrow diversity ofS. sylvestre, very high diversity ofS. strictum, and signatures of strong positive selection inS. vavilovii. Within cultivated ryes we detected the presence of genetic clusters and the influence of improvement status on the clustering. Rye landraces represent a reservoir of variation for breeding, and especially a distinct group of landraces from Turkey should be of special interest as a source of untapped variation. Selective sweep detection in cultivated accessions identified 133 outlier positions within 13 sweep regions and 170 putative candidate genes related, among others, to response to various environmental stimuli (such as pathogens, drought, cold), plant fertility and reproduction (pollen sperm cell differentiation, pollen maturation, pollen tube growth),and plant growth and biomass production.ConclusionsOur study provides valuable information for efficient management of rye germplasm collections, which can help to ensure proper safeguarding of their genetic potential and provides numerous novel candidate genes targeted by selection in cultivated rye for further functional characterisation and allelic diversity studies.
Empirically identifying and computationally modelling the brain-behaviour relationship for human scene categorization
Authors: Karapetian Agnessa , Boyanova Antoniya , Pandaram Muthukumar , Obermayer Klaus , Kietzmann Tim C. , Cichy Radoslaw M. 
Published: January 2023

AbstractHumans effortlessly make quick and accurate perceptual decisions about the nature of their immediate visual environment, such as the category of the scene they face. Previous research has revealed a rich set of cortical representations potentially underlying this feat. However, it remains unknown which of these representations are suitably formatted for decision-making. Here, we approached this question empirically and computationally, using neuroimaging and computational modelling. For the empirical part, we collected electroencephalography (EEG) data and reaction times from human participants during a scene categorization task (natural vs. man-made). We then related neural representations to behaviour using a multivariate extension of signal detection theory. We observed a correlation specifically between ∼100 ms and ∼200 ms after stimulus onset, suggesting that the neural scene representations in this time period are suitably formatted for decision-making. For the computational part, we evaluated a recurrent convolutional neural network (RCNN) as a model of brain and behaviour. Unifying our previous observations in an image-computable model, the RCNN predicted well the neural representations, the behavioural scene categorization data, as well as the relationship between them. Our results identify and computationally characterize the neural and behavioural correlates of scene categorization in humans.Significance statementCategorizing scene information is a ubiquitous and crucial task. Here we provide an empirical and computational account of scene categorization. Previous research has identified when scenes are represented in the visual processing hierarchy, but it remains unclear which of these representations are relevant for behaviour. We identified such representations between ∼100 ms and ∼200 ms after stimulus onset. We then showed that scene categorization in humans can be modelled via a recurrent convolutional neural network in a unified manner, i.e., in terms of neural and behavioural correlates, and their relationship. Together this reveals which representations underlie scene categorization behaviour and proposes a computational mechanism that implements such representations.
Cortical Representation of Movement Across the Developmental Transition to Continuous Neural Activity
Authors: Glanz Ryan , Sokoloff Greta , Blumberg Mark S. 
Published: January 2023

SummaryPrimary motor cortex (M1) exhibits a protracted period of development that includes the establishment of a somatosensory map long before motor outflow emerges. In rats, the sensory representation is established by postnatal day (P) 8 when cortical activity is still “discontinuous.” Here, we ask how the representation survives the sudden transition to noisy “continuous” activity at P12. Using neural decoding to predict forelimb movements based solely on M1 activity, we show that a linear decoder is sufficient to predict limb movements at P8, but not at P12; in contrast, a nonlinear decoder effectively predicts limb movements at P12. The change in decoder performance at P12 reflects an increase in both the complexity and uniqueness of kinematic information available in M1. We next show that the representation at P12 is more susceptible to the deleterious effects of “lesioning” inputs and to “transplanting” M1’s encoding scheme from one pup to another. We conclude that the emergence of continuous cortical activity signals the developmental onset in M1 of more complex, informationally sparse, and individualized sensory representations.
Serum albumin maintains Wnt water-solubility and activity
Authors: Yeo Joo Hye , Kwon Soon Sung , Chae Jiyeon , Kusen Ines , Han Jaeeun , Lim Ju Yeon , Cheong Jae-Ho , Kim Taeil , Jung Yang Ouk , Kim Chul Hoon , Lee Jinu 
Published: January 2023

SummaryWnt proteins regulate adult tissue homeostasis and repair by driving stem cell self-renewal and differentiation. High-performance Wnt preparations have enormous therapeutic potential, especially alongside various stem cell technologies. Currently, most of these Wnt preparations contain FBS or the detergent CHAPS to maintain Wnt solubility and activity. Recently, afamin was identified as a serum factor that solubilizes Wnt3a in conditioned media (CM), obviating the requirement for animal sera. Here, we report serum albumin (SA) is required for afamin-mediated solubilization of Wnt3a in CM. Moreover, SA-mediated solubilization of purified Wnt3a in tubes does not require afamin. This means conventional CHAPS-Wnt3a preparations can be modified into SA-purified Wnt3a (SA-pWnt3a) preparations by exchanging CHAPS for SA through dialysis. SA-pWnt3a preparations effectively promote the growth of human stem cell organoids. These data suggest SA as a physiological factor for maintaining Wnt3a activity in therapeutic applications.
Sensory constraints on volitional modulation of the motor cortex
Authors: Fisac Carmen F. , Chase Steven M. 
Published: January 2023

ABSTRACTVoluntary movement is driven by the primary motor cortex (M1), and individuals can learn to modulate even single neurons at will. Yet M1 also receives pronounced sensory inputs and contributes to sensory-driven motor responses. To what extent do these non-volitional signals restrict voluntary modulation of M1? Using a task in which the firing rate of a single neuron directly determines the position of a computer cursor along a visual axis, we assessed the ability of monkeys to modulate individual neurons under different sensory contexts. We found that sensory context persistently affected volitional control of single neurons in M1. For instance, visually rotating the biofeedback axis could render the same neural task effortless or problematic. Notably, extended training within or across days did not resolve this disparity. Our findings suggest that sensory context can limit the degree to which M1 activity is under volitional control.