bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of elevated embryonic incubation temperature on the temperature preference of juvenile lake (Coregonus clupeaformis) and round whitefish (Prosopium cylindraceum)
Authors: Harman Adam A. , Mahoney Hannah , Thompson William Andrew , Fuzzen Meghan L.M. , Aggarwhal Bhuvan , Laframboise Lisa , Boreham Douglas R. , Manzon Richard G. , Somers Christopher M. , Wilson Joanna Y. 
Published: March 2023

AbstractAnthropogenic impacts can lead to increased temperatures in freshwater environments through thermal effluent and climate change. Thermal preference of aquatic organisms can be modulated by abiotic and biotic factors including environmental temperature. Whether increased temperature during embryogenesis can lead to long-term alterations in thermal preference has not been explicitly tested in native freshwater species. Lake (Coregonus clupeaformis) and round (Prosopium cylindraceum) whitefish were incubated at natural and elevated temperatures until hatching, following which, all groups were moved to common garden conditions (15°C) during the post-hatching stage. Temperature preference was determined at 8 (Lake whitefish only) and 12-months of age (both species), using a shuttlebox system. Round whitefish preferred a cooler temperature when incubated at 2°C and 6°C compared to 0.5°C. Lake whitefish had similar temperature preferences regardless of age, weight, and incubation temperature. These results reveal that temperature preference in freshwater fish can be programmed during early development, and that round whitefish may be more sensitive to incubation temperature. This study highlights the effects that small increases in temperature caused by anthropogenic impacts may have on cold-adapted freshwater fish.
Evaluating performance and applications of sample-wise cell deconvolution methods on human brain transcriptomic data
Authors: Dai Rujia , Chu Tianyao , Zhang Ming , Wang Xuan , Jourdon Alexandre , Wu Feinan , Mariani Jessica , Vaccarino Flora M. , Lee Donghoon , Fullard John F. , Hoffman Gabriel E. , Roussos Panos , Wang Yue , Wang Xusheng , Pinto Dalila , Wang Sidney H. , Zhang Chunling ,   PsychENCODE consortium, Chen Chao , Liu Chunyu 
Published: March 2023

AbstractSample-wise deconvolution methods have been developed to estimate cell-type proportions and gene expressions in bulk-tissue samples. However, the performance of these methods and their biological applications has not been evaluated, particularly on human brain transcriptomic data. Here, nine deconvolution methods were evaluated with sample-matched data from bulk-tissue RNAseq, single-cell/nuclei (sc/sn) RNAseq, and immunohistochemistry. A total of 1,130,767 nuclei/cells from 149 adult postmortem brains and 72 organoid samples were used. The results showed the best performance of dtangle for estimating cell proportions and bMIND for estimating sample-wise cell-type gene expression. For eight brain cell types, 25,273 cell-type eQTLs were identified with deconvoluted expressions (decon-eQTLs). The results showed that decon-eQTLs explained more schizophrenia GWAS heritability than bulk-tissue or single-cell eQTLs alone. Differential gene expression associated with multiple phenotypes were also examined using the deconvoluted data. Our findings, which were replicated in bulk-tissue RNAseq and sc/snRNAseq data, provided new insights into the biological applications of deconvoluted data.
Shared input and recurrency in neural networks for metabolically efficient information transmission
Authors: Barta Tomas , Kostal Lubomir 
Published: March 2023

AbstractShared input to a population of neurons induces noise correlations, which decreases the information carried by a population activity. Inhibitory feedback in recurrent neural networks can reduce the noise correlations and thus increase the information carried by the averaged population activity. However, the activity of inhibitory neurons is costly. This inhibitory feedback decreases the gain of the population. Thus, depolarization of its neurons requires stronger excitatory synaptic input, which is associated with higher ATP consumption. Given that the goal of neural populations is to transmit as much information as possible at minimal metabolic costs, it is unclear whether the increased information transmission reliability provided by inhibitory feedback compensates for the additional costs. We analyze this problem in a network of leaky integrate-and-fire neurons receiving correlated input. By maximizing mutual information with metabolic cost constraints, we show that there is an optimal strength of recurrent connections in the network, which maximizes the value of mutual information-per-cost. For higher values of input correlation, the mutual information-per-cost is higher for recurrent networks with inhibitory feedback compared to feedforward networks without any inhibitory neurons. Our results, therefore, show that the optimal synaptic strength of a recurrent network can be inferred from metabolically efficient coding arguments and that decorrelation of the input by inhibitory feedback compensates for the associated increased metabolic costs.
Dynamical flexible inference of nonlinear latent structures in neural population activity
Authors: Abbaspourazad Hamidreza , Erturk Eray , Pesaran Bijan , Shanechi Maryam M. 
Published: March 2023

AbstractInferring complex spatiotemporal dynamics in neural population activity is critical for investigating neural mechanisms and developing neurotechnology. These activity patterns are noisy observations of lower-dimensional latent factors and their nonlinear dynamical structure. A major unaddressed challenge is to model this nonlinear structure, but in a manner that allows for flexible inference, whether causally, non-causally, or in the presence of missing neural observations. We address this challenge by developing DFINE, a new neural network that separates the model into dynamic and manifold latent factors, such that the dynamics can be modeled in tractable form. We show that DFINE achieves flexible nonlinear inference across diverse behaviors and brain regions. Further, despite enabling flexible inference unlike prior neural network models of population activity, DFINE also better predicts the behavior and neural activity, and better captures the latent neural manifold structure. DFINE can both enhance future neurotechnology and facilitate investigations across diverse domains of neuroscience.
Optineurin deficiency impairs autophagy to cause interferon beta overproduction and increased survival of mice following viral infection
Authors: Fukushi Masaya , Ohsawa Ryosuke , Okinaka Yasushi , Oikawa Daisuke , Kiyono Tohru , Moriwaki Masaya , Irie Takashi , Oda Kosuke , Kamei Yasuhiro , Tokunaga Fuminori , Sotomaru Yusuke , Maruyama Hirofumi , Kawakami Hideshi , Sakaguchi Takemasa 
Published: March 2023

AbstractBackgroundOptineurin (OPTN) is associated with several human diseases, including amyotrophic lateral sclerosis (ALS), and is involved in various cellular processes, including autophagy. Optineurin regulates the expression of interferon beta (IFNβ), which plays a central role in the innate immune response to viral infection. However, the role of optineurin in response to viral infection has not been fully clarified. It is known that optineurin-deficient cells produce more IFNβ than wild-type cells following viral infection. In this study, we investigate the reasons for, and effects of, IFNβ overproduction during optineurin deficiency bothin vitroandin vivo.MethodsTo investigate the mechanism of IFNβ overproduction, viral nucleic acids in infected cells were quantified by RT-qPCR and the autophagic activity of optineurin-deficient cells was determined to understand the basis for the intracellular accumulation of viral nucleic acids. Moreover, lethal viral infection experiments using optineurin-disrupted (Optn-KO) animals were performed.ResultsIFNβ overproduction following viral infection was observed not only in several types of optineurin-deficient cell lines but also inOptn-KO mice and human ALS patient cells carrying mutations inOPTN. IFNβ overproduction inOptn-KO cells was revealed to be caused by excessive accumulation of viral nucleic acids, which was a consequence of reduced autophagic activity caused by the loss of optineurin. Additionally, IFNβ overproduction inOptn-KO mice suppressed viral proliferation, resulting in increased mouse survival following lethal viral challenge.ConclusionOur findings indicate that the combination of optineurin deficiency and viral infection leads to IFNβ overproductionin vitroandin vivo. The effects of optineurin deficiency are elicited by viral infection, therefore, viral infection may be implicated in the development of optineurin-related diseases.
Immune profiling, microbiome, metabolomics, and gut physiology of a 1-year controlled human hookworm infection
Authors: Vacca Francesco , Lavender Brittany , Noble Sophia-Louise , Cait Alissa , Maclean Kate , Mamum John , Yumnam Bibek , Kawa Tama Te , Mules Thomas C , Ferrer-Font Laura , Tang Jeffry S. , Gasser Olivier , Gros Graham Le , Camberis Mali , Inns Stephen 
Published: March 2023

AbstractThe observation that experimental helminth infection can be associated with immunomodulation and suppression of inflammatory diseases at distal tissue sites, has been used as rationale for trialing helminths such asNecator americanusfor the treatment of inflammatory disorders in humans. However, the lack of sufficient knowledge of the immunological interplay between human host and parasite in a controlled infection setting limits ongoing clinical intervention studies. In this one-year longitudinal study, healthy volunteers were recruited and infected withN. americanus. Changes in immune responses, microbiome, plasma metabolome and gut physiology were examined over the course of the one-year period. All participants were successfully infected as confirmed by detectable eggs in the feces and adult worms visualized in the intestine. In general, individual variation in immune cells, serum cytokines, fecal microbiome and plasma metabolites were greater than changes induced by the infection. Nevertheless, eosinophils, serum IL-5, and fecal eosinophil degranulation markers transiently increased in the acute phase of infection. In addition, while we observed stability in microbial community composition through the course of infection, we found a difference in the microbial community composition of participants with moderate gastrointestinal symptoms. No significant changes were observed in gut physiology measured using SmartpillTM, except for a decrease in small bowel pH. Untargeted plasma metabolomics analysis of participant plasma over the course of infection revealed enrichment in tryptophan metabolism following infection which was associated with increased CTLA-4 expression on regulatory T cells (TREGS), CRTH2+T helper 2 cells (TH2) and CCR6+T helper 9 cells (TH9). In conclusion, hookworm infection is well tolerated and represents an innovative platform for investigating immunomodulatory properties of hookworm infection in a therapeutic clinical setting.One Sentence SummaryControlled human hookworm infection changes immune-linked metabolic pathways
Direction and distance dependency of reaching movements of lower limb
Authors: Oku Kyosuke , Tanaka Shinsuke , Kida Noriyuki 
Published: March 2023

AbstractEfficient movement of the body is an important part of our daily lives, which we perform unconsciously. Such efficient movements have been investigated using reaching movements in the upper limb, and whose kinematics reportedly vary depending on the movement direction. However, the reaching movements of the lower limbs are not well understood. Therefore, we aimed to examine changes in the kinematics of the lower limb reaching movements to determine the mechanism of skilled motor ability in terms of direction and distance. Sixteen adults (10 males) were requested to reach targets projected on the floor in seven directions and at three distances, for a total of 21 points. We found that the reaching time slowed down for the contralateral side (right foot to left-sided target), and was caused by a slower start of the toe movement. To identify the cause of this delay, we analyzed the onset of movement at each joint and found that movement to the contralateral side began closer to the torso than movement to the ipsilateral side. The time-to-peak velocity was also calculated; the motion required to reach the target in the shortest time varied depending on the direction and distance. Acceleration phases that were not observed in the upper limb velocity profile were observed in the lower limb velocity profiles. These results suggest that movement kinematics vary with direction and distance, resulting in slower reaching time on the contralateral side.
Short-chain mono-carboxylates as negative modulators of allosteric transitions in GLIC, and impact of a pre-β5 strand (Loop Ω) double mutation on crotonate, not butyrate effect
Authors: Renterghem Catherine Van , Nemecz Ákos , Medjebeur Karima , Corringer Pierre-Jean 
Published: March 2023

AbstractThe bacterial model GLIC remains one of the best known among pentameric ligand-gated ion channels (pLGICs), regarding their structure. GLIC is activated at low extracellular pH, but no agonist compound is known. Van Renterghemet al. (2023) showed that short-chain di-carboxylates potentiate GLIC activity, with strict dependence on two carboxylate binding pockets, previously characterized by crystallography (Sauguetet al., 2013, Fouratiet al., 2015, 2020). An “in series” model was proposed, with compound binding at the inter-subunit pocket [homologous to the pLGICs orthotopic neutotransmitter binding site], and with involvement of the intra-subunit (or vestibular) pocket in coupling binding to gating.Here we characterize saturated, mono-carboxylates as negative modulators of GLIC, as previously shown for crotonate (Alqazzazet al., 2016). Butyrate and crotonate have indistinguishable properties regarding negative modulation of WT GLIC. However, a double mutation in the pre-β5 strand (Loop Ω) converts crotonate, as well as caffeate, but not butyrate, into positive modulators. We perform a mutational analysis of residue dependency in the two pockets, with the pre-β5 strand either intact or mutated. We propose that positive modulation requires stringent conditions, with integrity of both pockets, whereas negative modulation is less labile. The vestibular pocket may be involved as an accessory binding site leading to negative, but not positive modulation. We propose that the pre-β5 strand is involved in ligand-elicited modulation of GLIC gating, not in pHo-controlled gating. Possible involvement in Eukaryote pLGICs of regions corresponding to the vestibular pocket and the pre-β5 strand/Loop Ω is discussed.Key points summaryUsing the bacterial proton-activated receptor-channel GLIC, we identify a locus in the pre-β5 strand (Loop Ω) whose mutation inverses the effect of the mono-carboxylate crotonate from negative to positive modulation of the allosteric transitions, suggesting an involvement of the pre-β5 strand in coupling the extracellular orthotopic receptor to pore gating in this pentameric ligand-gated ion channel.As an extension to the previously proposed “in series” mechanism, we suggest that a orthotopic/orthosteric site – vestibular site – Loop Ω – β5-β6 “sandwich” - Pro-Loop/Cys-Loop series may be an essential component of orthotopic/orthosteric compound-elicited gating control in this pentameric ligand-gated ion channel, on top of which compounds targeting the vestibular site may provide modulation.
Uneven terrain versus dual-task walking: differential challenges imposed on walking behavior in older adults are predicted by cognitive and sensorimotor function
Authors: Shah Valay A , Cruz-Almeida Yenisel , Roy Arkaprava , Cenko Erta , Downey Ryan J , Ferris Daniel P , Hass Chris J , Reuter-Lorenz Patricia A. , Clark David J , Manini Todd M , Seidler Rachael D 
Published: March 2023

AbstractAging is associated with declines in walking function. To understand these mobility declines, many studies have obtained measurements while participants walk on flat surfaces in laboratory settings during concurrent cognitive task performance (dual-tasking). This may not adequately capture the real-world challenges of walking at home and around the community. Here, we hypothesized that uneven terrains in the walking path impose differential changes to walking speed compared to dual-task walking. We also hypothesized that changes in walking speed resulting from uneven terrains will be better predicted by sensorimotor function than cognitive function. Sixty-three community-dwelling older adults (65-93 yrs old) performed overground walking under varying walking conditions. Older adults were classified into two mobility function groups based on scores of the Short Physical Performance Battery. They performed uneven terrain walking across four surface conditions (Flat, Low, Medium, and High unevenness) and performed single and verbal dual-task walking on flat ground. Participants also underwent a battery of cognitive (cognitive flexibility, working memory, inhibition) and sensorimotor testing (grip strength, 2-pt discrimination, pressure pain threshold). Our results showed that walking speed decreased during both dual-task walking and across uneven terrain walking conditions compared to walking on flat terrain. Participants with lower mobility function had even greater decreases in uneven terrain walking speeds. The change in uneven terrain speed was associated with attention and inhibitory function. Changes in both dual-task and uneven terrain walking speeds were associated with 2-point tactile discrimination. This study further documents associations between mobility, executive functions, and somatosensation, highlights the differential costs to walking imposed by uneven terrains, and identifies that older adults with lower mobility function are more likely to experience these changes to walking function.
Epigenetic reprogramming of a distal developmental enhancer cluster drivesSOX2overexpression in breast and lung cancer
Authors: Abatti Luis E. , Lado-Fernández Patricia , Huynh Linh , Collado Manuel , Hoffman Michael M. , Mitchell Jennifer A. 
Published: March 2023

ABSTRACTEnhancer reprogramming has been proposed as a key source of transcriptional dysregulation during tumorigenesis, but the molecular mechanisms underlying this process remain unclear. Here, we identify an enhancer cluster required for normal development that is aberrantly activated in breast and lung carcinoma. Deletion of the SRR124–134 cluster disrupts transcription of theSOX2oncogene and dysregulates genome-wide chromatin accessibility in cancer cells. Analysis of primary tumors reveals a correlation between chromatin accessibility at this cluster andSOX2overexpression in breast and lung cancer patients. We demonstrate that FOXA1 is an activator and NFIB is a repressor of SRR124–134 activity andSOX2transcription in cancer cells, revealing a co-opting of the regulatory mechanisms involved in early development. Notably, we show that the conserved SRR124 and SRR134 regions are essential during mouse development, where homozygous deletion results in the lethal failure of esophageal-tracheal separation. These findings provide insights into how developmental enhancers can be reprogrammed during tumorigenesis and underscore the importance of understanding enhancer dynamics during development and disease.
A newPlasmodium vivaxreference genome for South American isolates
Authors: De Meulenaere Katlijn , Cuypers Bart , Gamboa Dionicia , Laukens Kris , Rosanas-Urgell Anna 
Published: March 2023

AbstractBackgroundPlasmodium vivaxis the second most important cause of human malaria worldwide, and accounts for the majority of malaria cases in South America. A high-quality reference genome exists for Papua Indonesia (PvP01) and Thailand (PvW1), but is lacking for South America. A reference genome specifically for South America would be beneficial though, asP. vivaxis a genetically diverse parasite with geographical clustering.ResultsThis study presents a new high-quality assembly of a South AmericanP. vivaxisolate, referred to as PvPAM. The genome was obtained from a low input patient sample from the Peruvian Amazon and sequenced using PacBio technology, resulting in a highly complete assembly with 6497 functional genes. Telomeric ends were present in 17 out of 28 chromosomal ends, and additional (sub)telomeric regions are present in 12 unassigned contigs. A comparison of multigene families between PvPAM and the PvP01 genome revealed remarkable variation invirgenes, and the presence of merozoite surface proteins (MSP) 3.6 and 3.7. Threedhfranddhpsdrug resistance associated mutations are present in PvPAM, similar to those found in other Peruvian isolates. Mapping of publicly available South American whole genome sequencing (WGS) data to PvPAM resulted in significantly fewer variants and truncated reads compared to the use of PvP01 or PvW1 as reference genomes. To minimize the number of core genome variants in non-South American samples, PvW1 is most suited for Southeast Asian isolates, both PvPAM and PvW1 are suited for South Asian isolates, and PvPAM is recommended for African isolates. Interestingly, non-South American samples still contained the least subtelomeric variants when mapped to PvPAM, indicating high quality of the PvPAM subtelomeric regions.ConclusionsOur findings show that the PvPAM reference genome more accurately represents South AmericanP. vivaxisolates in comparison to PvP01 and PvW1. In addition, PvPAM has a high level of completeness, and contains a similar number of annotated genes as PvP01 or PvW1. The PvPAM genome therefore will be a valuable resource to improve future genomic analyses onP. vivaxisolates from the South American continent.
Protein-specific signal peptides for mammalian vector engineering
Authors: O’Neill Pamela , Mistry Rajesh K , Brown Adam J. , James David C. 
Published: March 2023

ABSTRACTExpression of recombinant proteins in mammalian cell factories relies on synthetic assemblies of genetic parts to optimally control flux through the product biosynthetic pathway. In comparison to other genetic part-types, there is a relative paucity of characterized signal peptide components, particularly for mammalian cell contexts. In this study, we describe a toolkit of signal peptide elements, created using bioinformatics-led and synthetic design approaches, that can be utilized to enhance production of biopharmaceutical proteins in Chinese Hamster Ovary cell factories. We demonstrate, for the first time in a mammalian cell context, that machine learning can be used to predict how discrete signal peptide elements will perform when utilized to drive ER translocation of specific single chain protein products. For more complex molecular formats, such as multichain monoclonal antibodies, we describe how a combination ofin silicoand targeted design rule-basedin vitrotesting can be employed to rapidly identify product-specific signal peptide solutions from minimal screening spaces. The utility of this technology is validated by deriving vector designs that increase product titers ≥ 1.8x, compared to standard industry systems, for a range of products, including a difficult-to-express monoclonal antibody. The availability of a vastly expanded toolbox of characterized signal peptide parts, combined with streamlinedin silico/in vitrotesting processes, will permit efficient expression vector re-design to maximize titers of both simple and complex protein products.GRAPHICAL ABSTRACT