bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CMOS-based highly scalable flexible neural electrode interface
Authors: Zhao Eric T. , Hull Jacob , Hemed Nofar Mintz , Uluşan Hasan , Bartram Julian , Zhang Anqi , Wang Pingyu , Pham Albert , Ronchi Silvia , Huguenard John R. , Hierlemann Andreas , Melosh Nicholas A. 
Published: November 2022

AbstractPerception, thoughts, and actions are encoded by the coordinated activity of large neuronal populations spread over large areas. Using thin film electrocorticography (ECoG) arrays, this cortical activity has been used to decode speech and individual finger movements, enabling neuroprosthetics, and to localize epileptic foci. However, the connectorization of these multi-thousand channel thin-film arrays to external circuitry is challenging; current state-of-the-art methods are complex, bulky, and unscalable. We address this shortcoming by developing an electrode connector based on an ultra-conformable thin film electrode array that self-assembles onto hard silicon chip sensors, such as microelectrode arrays (MEAs) or camera sensors enabling large channel counts at high density. The interconnects are formed using microfabricated electrode pads suspended by thin support arms, termed flex2chip. Capillary-assisted assembly drives the pads to deform towards the chip surface, and van der Waals forces maintain this deformation, establishing mechanical and Ohmic contact onto individual pixels. We demonstrate a 2200-channel array with a channel density of 272 channels / mm2connected to the MEA through the flex2chip interconnection method. Thin film electrode arrays connected through the flex2chip successfully measured extracellular action potentials ex vivo. Furthermore, in a transgenic mouse model for absence epilepsy,Scn8a+/-, we observed highly variable propagation trajectories at micrometer scales, even across the duration of a single spike- and-wave discharge (SWD).
Target-distractor competition modulates saccade trajectories in space and object-space
Authors: Giuricich Caroline , Green Robert J. , Jordan Heather , Fallah Mazyar 
Published: November 2022

AbstractSaccade planning and execution can be affected by a multitude of factors present in a target selection task. Recent studies have shown that the similarity between a target and nearby distractors affects the curvature of saccade trajectories, due to target-distractor competition. To further understand the nature of this competition, we varied the distance between and the similarity of complex target and distractor objects in a delayed match-to-sample task to examine their effects on saccade trajectories and better understand the underlying neural circuitry. For trials with short saccadic reaction times (SRTs) when target-distractor competition is still active, we found a robust effect of distance consistent with saccade vector averaging, whereas the effect of similarity suggested the existence of an object-based suppressive surround. At longer SRTs there was sufficient time for competition between the objects to complete and the distractor to be inhibited, which resulted in saccade trajectory deviations exhibiting the effects of a spatial suppressive surround. In terms of similarity, as the target-distractor similarity decreased, the initial saccade angle shifted towards the target, reflecting stronger distractor inhibition. There were no interactions between distance and similarity at any point in the time-course of target-distractor competition. Taken together, saccade trajectories reflect target-distractor competition that is affected independently by both spatial and object-space suppressive surrounds. The differences in saccade trajectories at short and long SRTs distinguish between active and completed decision-making processes. Thus, saccade responses are more beneficial than manual responses in studies of decision-making models.Significance StatementThis is the first study to determine that the distance and similarity between visual objects independently affect saccade trajectories driven by the target-distractor competition process. Thus, spatiotemporal and object identity factors separately feed into saccade planning and execution, resulting in modulations of saccade trajectory metrics which are based on spatial and object-space suppressive surround mechanisms. Furthermore, this modulation of trajectory metrics distinguishes between active and complete decision-making processes. The findings are important for understanding the dynamic networks guiding target selection and are relevant for further development of decision-making models, as well as eye-tracking applications in health and disease.
gMCStool: automated network-based tool to search for metabolic vulnerabilities in cancer
Authors: Valcárcel Luis V. , José-Enériz Edurne San , Ordoñez Raquel , Apaolaza Iñigo , Valcárcel Ana , Garate Leire , San Miguel Jesús , Pineda-Lucena Antonio , Agirre Xabier , Prósper Felipe , Planes Francisco J. 
Published: November 2022

ABSTRACTThe development of computational tools for the systematic prediction of metabolic vulnerabilities of cancer cells constitutes a central question in systems biology. Here, we presentgMCStool, a freely accessible and online tool that allows us to carry out this task in a simple, efficient and intuitive environment.gMCStoolexploits the concept of genetic Minimal Cut Sets (gMCSs), a theoretical approach to synthetic lethality based on genome-scale metabolic networks, including a unique database of thousands of synthetic lethals computed from Human1, the most recent metabolic reconstruction of human cells. Based on RNA-seq data,gMCStoolextends and improves our previously developed algorithms to predict, visualize and analyze metabolic essential genes in cancer, demonstrating a superior performance than competing algorithms in both accuracy and computational performance. A detailed illustration ofgMCStoolis presented for multiple myeloma (MM), an incurable hematological malignancy. gMCStool could identify a synthetic lethal that explains the dependency on CTP Synthase 1 (CTPS1) in a sub-group of MM patients. We providein vitroexperimental evidence that supports this hypothesis, which opens a new research area to treat MM.
Integrated protein-protein interaction and RNA interference screens reveal novel restriction and dependency factors for a tick-borne flavivirus in its human host
Authors: Sourisseau Marion , Unterfinger Yves , Lemasson Manon , Caignard Gregory , Piumi François , Grot Axel , Moutailler Sara , Vitour Damien , Coulpier Muriel , Lacour Sandrine A. , Richardson Jennifer 
Published: November 2022

ABSTRACTIn Europe, tick-borne encephalitis virus (TBEV) is responsible for severe neurological disease in humans. Like other viruses, TBEV is an obligate intracellular life form whose survival requires subversion of metabolic processes and evasion of anti-viral pathways. This feat is achieved in no small part by binary interactions between dedicated viral proteins and host proteins. Such protein-protein interactions (PPI) constitute molecular determinants of critical pathobiologic traits of viruses, including host-range, zoonotic potential and virulence, and represent realistic targets for anti-viral therapies.To shed light on the pathobiology of TBEV in human, we have resolved the network of PPI established with its human host by interaction proteomics. A high-throughput screen for virus-host PPI was performed involving the complete set of open reading frames of TBEV and the cDNA libraries ofHomo sapiens, by means of yeast two-hybrid methodology. We have discovered a large set of virus-host protein-protein interactions concerning 42 different human proteins directly interacting with nine viral proteins. Many of these human interactors have never been linked in the literature to viral infection.The functional significance of the host interactors in viral infection as viral dependency or restriction factors was then characterizedin vitroby RNA interference, and their function inferred by bioinformatic analysis. Approximately 40% of the identified human proteins have a significative impact on TBEV viral replication. These are engaged in many biological processes, whose involvement in viral infection is expected for many, but enigmatic for some. Further work will be necessary to gain molecular understanding of how these biological processes support or restrict TBEV replication, and whether they constitute viral vulnerabilities that can be exploited therapeutically.
SOX9 elongates cell cycle phases and biases fate decisions in human intestinal stem cells
Authors: Burclaff Joseph , Bliton R. Jarrett , Breau Keith A , Cotton Michael J , Hinesley Caroline M , Ok Meryem T , Sweet Caden W , Zheng Anna , Bankaitis Eric D , Ariel Pablo , Magness Scott T 
Published: November 2022

ABSTRACTBackground and AimsThe transcription factor SOX9 is expressed in many stem/progenitor cell populations and has biphasic correlations with proliferation rates across different biological systems. In murine intestinal crypts, distinct Sox9 levels mark three phenotypically different cell types, with lowest levels marking rapidly-dividing transit amplifying (TA) cells, intermediate levels marking intestinal stem cells (ISCs), and highest levels marking slowly-dividing label retaining secretory precursors. SOX9 expression levels and the impact of these levels on cell cycle and stem cell activity have not been characterized for humans.MethodsMonolayers of primary human ISCs isolated from healthy organ donors were engineered with stable SOX9-knockout (KO) and/or SOX9-overexpression (OE) genomic modifications to assess the impact of SOX9 levels on proliferative capacity by DNA content analysis, cell cycle phase length by live imaging for a PIP-FUCCI reporter, stem cell activity via organoid formation assays, and cell fate after ISC differentiation tracked via qPCR.ResultsSOX9 was expressed at diverse levels in human intestinal crypt lineages in vivo, repressed proliferation in human ISC monolayers, and predominantly lengthened G1 by >40% with lesser lengthening of S and G2/M phases. Overexpression of SOX9 caused slower proliferation yet increased organoid forming efficiency. Higher SOX9 levels biased ISC differentiation towards tuft cell and follicle-associated epithelium fates while loss of SOX9 biased cells toward absorptive enterocyte, goblet cell, BEST4+cell, and enteroendocrine cell fates.ConclusionsSOX9 is a master regulator of stem cell activity in human ISCs, lengthening the cell cycle, promoting stemness, and altering differentiation fate. Interestingly, differences are noted between species, highlighting the importance of analyzing regulatory mechanisms in primary healthy human cells.
Three decades of increasing fish biodiversity across the north-east Atlantic and the Arctic Ocean
Authors: Gordó-Vilaseca Cesc , Stephenson Fabrice , Coll Marta , Lavin Charles , Costello Mark John 
Published: November 2022

AbstractObserved range shifts of numerous species support predictions of climate change models that species will shift their distribution northwards into the Arctic and sub-Arctic seas due to ocean warming. However, how this is affecting overall species richness is unclear. Here we analyse scientific research trawl surveys from the North Sea to the Arctic Ocean collected from 1994 to 2020, including 193 fish species. We found that demersal fish species richness at the local scale has doubled in some Arctic regions, including the Barents Sea, and increased at a lower rate at adjacent regions in the last three decades, followed by an increase in species richness and turnover at a regional scale. These changes in biodiversity paralleled an increase in sea bottom temperature. Within the study area, Arctic species’ probability of occurrence generally declined over time. However, the increase of species from southern latitudes, together with an increase of some Arctic species, ultimately led to an enrichment of the Arctic and sub-Arctic marine fauna due to increasing water temperature consistent with climate change.Significance StatementGlobal modelling studies suggest increased species arrivals from lower latitudes and local expirations at high latitudes due to global warming. Our analysis of 20,670 standardized scientific trawl surveys with 193 fish species from the north-east Atlantic and Arctic Oceans found an increase in species richness in the region parallel to an increase in sea bottom temperature. Some Arctic species declined in probability of occurrence over time, but some increased. This, together with the increase of southern-latitude species led to an enrichment of the Arctic and sub-Arctic marine fauna attributed to climate change.
The DNA binding protein BCL6 regulates NFκB-controlled endothelial inflammatory gene expression
Authors: Acevedo Adriana Franco , Mack Julia J. , Valenzuela Nicole M 
Published: November 2022

AbstractBackgroundNFκB drives acute vascular inflammation by activating gene expression programs in endothelial cells to promote leukocyte recruitment. Numerous negative feedback regulators of NFκB activation have been defined that promote resolution of inflammation. However, the identities of endogenous suppressors of NFκB transcription are less clear. In macrophages, the transcriptional repressor BCL6 was shown to substantially overlap with NFκB-driven genes and influence the response to LPS. We identified that the DNA binding protein BCL6 was expressed in endothelial cells. Although the role of BCL6 in adaptive immune cells has been characterized, how BCL6 modifies transcription in endothelial cells has not been studied.ObjectiveBased on prior knowledge that BCL6 represses part of the LPS-induced transcriptome in macrophages, we asked whether BCL6 regulated endothelial pro-inflammatory state by direct interaction with NFκB.MethodsWe analyzed public datasets of RNA and ChIP-Seq, probed BCL6 expression in human tissue, and tested BCL6 knockdown, overexpression and pharmacological manipulation on TNFα induced gene expressionin vitrousing human primary endothelium isolated from the heart.ResultsWe demonstrate that the DNA binding protein BCL6 is basally expressed in the endothelium, with chromatin marks reflective of a superenhancer, and is particularly enriched in aortic endothelial cells (ECs) compared with ECs from other organs. Although basal expression was relatively low, BCL6 was rapidly upregulated in cardiac endothelium stimulated with TNFα, through direct action of NFκB. The BCL6 consensus DNA binding motif overlaps with that of NFκB. BCL6 target genes included endothelial pro-inflammatory chemokines and adhesion molecules, as well as NFκB-related genes themselves. BCL6 knockdown and the degrading BCL6 inhibitor BI-3802 augmented the endothelial cell response to TNFα. Surprisingly, antagonism of the BTB domain of BCL6 with small molecules 79-6, FX1 or BI-3812, blocked leukocyte adherence and accordingly suppressed both NFκB transcriptional activity as well as the expression of many genes in response to TNFα. Lastly, we show that HDAC activity is increased by TNFα, and can be reduced in the presence of BTB domain inhibitors.ConclusionsOur results demonstrate that BCL6 is a repressor of NFκB-driven gene expression and inflammation in cardiac endothelial cells. These findings indicate that targeting of BCL6 may enhance vascular inflammation resolution.
Chytrids-conveyed long-chain polyunsaturated fatty acids to Daphnia alleviate the detrimental effect of heat when combined with limiting dietary organic matter quantity and nutritional quality
Authors: Abonyi András , Pilecky Matthias , Rasconi Serena , Ptacnik Robert , Kainz Martin J. 
Published: November 2022

AbstractGlobal warming enhances the dominance of poorly palatable PUFA-deprived bloom-forming cyanobacteria. Chytrid fungal parasites increase herbivory and dietary access to polyunsaturated fatty acids (PUFA) across the phytoplankton-zooplankton interface. Little is known however about the role chytrids may play in compensating for the decrease of algae-derived PUFA under global warming scenarios. We tested experimentally the combined effects of water temperature increase and the presence of chytrids withDaphnia magnaas the consumer and the cyanobacteriumPlanktothrix rubescensas the main diet. We hypothesised that the diet including chytrids would enhanceDaphniafitness due to increased PUFA transfer irrespective of water temperature. Chytrid-infected diet significantly increasedDaphniasurvival, somatic growth, and reproduction, irrespective of water temperature. The PUFA content ofDaphniafeeding on the chytrid-infected diet was unaffected by heat at the onset of the first successful reproduction. Carbon stable isotopes of fatty acids highlighted preferential n-3 PUFA upgrading by chytrids and an ~3x higher endogenous n-3 PUFA conversion compared with n-6 PUFA byDaphnia, irrespective of water temperature. Diet including chytrids enhanced the retention of eicosapentaenoic acid (EPA; 20:5n-3) and arachidonic acid (ARA; 20:4n-6) inDaphnia. The heat did not decrease EPA and even increased ARA retention by enhanced endogenous bioconversion inDaphniawhen feeding on the chytrid-infected diet. We conclude that chytrids supportDaphniafitness at higher water temperatures via increased n-3 and n-6 PUFA retention and preferential n-3 PUFA bioconversion. Thus, they help function pelagic ecosystems with PUFA availability at the phytoplankton-zooplankton interface in a warmer climate.
An improved Erk biosensor reveals oscillatory Erk dynamics driven by mitotic erasure during early development
Authors: Wilcockson Scott G. , Guglielmi Luca , Rodriguez Pablo Araguas , Amoyel Marc , Hill Caroline S. 
Published: November 2022

AbstractErk signaling dynamics elicit distinct cellular responses in a variety of contexts. The early zebrafish embryo is an ideal model to explore the role of Erk signaling dynamicsin vivo, as a gradient of activated diphosphorylated Erk (P-Erk) is induced by Fgf signaling at the blastula embryonic margin. Here we describe an improved Erk-specific biosensor which we term modified Erk Kinase Translocation Reporter (modErk-KTR). We demonstrate the utility of this biosensorin vitroand in developing zebrafish andDrosophilaembryos. Moreover, we show that Fgf/Erk signaling is dynamic and coupled to tissue growth during both early zebrafish andDrosophiladevelopment. Signaling is rapidly extinguished just prior to mitosis, which we refer to as mitotic erasure, inducing periods of inactivity, thus providing a source of heterogeneity in an asynchronously dividing tissue. Our modified reporter and transgenic lines represent an important resource for interrogating the role of Erk signaling dynamicsin vivo.
Transcriptomic landscape of early hair follicle and epidermal development
Authors: Sulic Ana-Marija , Roy Rishi Das , Papagno Verdiana , Lan Qiang , Saikkonen Riikka , Jernvall Jukka , Thesleff Irma , Mikkola Marja L 
Published: November 2022

SUMMARYMorphogenesis of ectodermal organs, such as hair, tooth, and mammary gland, starts with the formation of local epithelial thickenings, or placodes, but it remains to be determined how distinct cell types and differentiation programs are established during ontogeny. Here, we use bulk and single-cell transcriptomics and pseudotime modelling to address these questions in developing hair follicles and epidermis, and produce a comprehensive transcriptomic profile of cellular populations in the hair placode and interplacodal epithelium. We report previously unknown cell populations and marker genes, including early suprabasal and genuine interfollicular basal markers, and propose the identity of suprabasal progenitors. By uncovering four different hair placode cell populations organized in three spatially distinct areas, with fine gene expression gradients between them, we posit early establishment of cell fates. This work is accompanied by a readily accessible online tool to stimulate further research on skin appendages and their progenitors.
Glucocorticoid involvement in reproductive biology
Authors: Mullins Linda J. , Morley Steven D. , Kenyon Christopher J. , Mullins John J. 
Published: November 2022

AbstractOestrogen and progesterone play essential roles in the release of mature oocytes, the priming and cycling of the uterine lining, and the maintenance of mammalian pregnancy. Progesterone is synthesizedde novoat the embryo implantation site in the mouse, during decidualization of the endometrium. During early stages of pregnancy, the locally produced progesterone is thought to act as an immunosuppressant, preventing rejection of the fetal allograft at the fetal-maternal interface. However, both uterine natural killer cells and dendritic cells express glucocorticoid receptor rather than progesterone receptor. The importance of glucocorticoids in early pregnancy is inferred from the presence of steroid receptors and the 11β-hydroxysteroid dehydrogenase enzymes, which modulate corticosterone action in the decidua, the trophoblast, the placenta, and the fetus. 11β-hydroxylase is the last enzyme in the metabolism of cholesterol to corticosterone and, in a mouse model of 11β-hydroxylase deficiency, complications of reproduction suggested its requirement for normal ovulation and uterine cell turnover. We present evidence that, in this model, folliculogenesis occurs normally but ovulation is inhibited, and abnormal uterine cell turnover ultimately leads to adenomyosis. Ovaries respond to a superovulation protocol by releasing oocytes and forming corpora lutea, and homozygous null blastocysts are capable of implantation, but the pregnancy is not maintained. We show that glucocorticoid is produced locally at the implantation site in control animals, revealing wide involvement of glucocorticoids in reproductive biology.
Body mass decline in a Mediterranean community of solitary bees supports the size shrinking effect of climatic warming
Authors: Herrera Carlos M. , Núñez Alejandro , Valverde Javier , Alonso Conchita 
Published: November 2022

AbstractThe long-known, widely documented inverse relationship between body size and environmental temperature (“temperature-size rule”) has recently led to predictions of body size decline following current climatic warming (“size shrinking effect”). For keystone pollinators such as wild bees, body shrinking in response to warming can have pervasive effects on pollination processes, but there is still little evidence of the phenomenon because adequate tests require controlling for climate-linked confounding factors (e.g., urbanization, land use change). This paper tests the shrinking effect in a diverse community of solitary bees from well-preserved habitats in the core of a large nature reserve undergoing fast climatic warming but not disturbances or habitat changes. Long-term variation in mean body mass was evaluated using data from 1,186 individual bees (108 species, 25 genera, 6 families) sampled over 1990-2022. Climate of the region warmed at a fast rate during this period and changes in bee body mass verified expectations from the size shrinking effect. Mean individual body mass of the regional community of solitary bees declined significantly, shrinking being particularly intense for female individuals and large-bodied species. As a consequence, the pollination and mating systems of many bee-pollinated plants in the region are likely undergoing important alterations.