bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of co-incubation of LPS-stimulated RAW 264.7 macrophages on leptin production by 3T3-L1 adipocytes: A method for co-incubating distinct adipose tissue cell lines
Authors: Caldari-Torres Cristina , Beck Jordan 
Published: July 2021

AbstractAdipose tissue is a major endocrine organ capable of releasing inflammatory adipokines. Inflammatory adipokine release is linked to the changes occurring in adipose tissue in the overfed state, where tissue remodeling results in hypertrophic adipocytes that recruit monocytes to infiltrate the tissue and take on an inflammatory phenotype. As the proportion of inflammatory macrophages increases there is a concurrent increase in release of macrophage-specific inflammatory mediators, further contributing to the inflamed state and setting an inflammatory loop between the macrophages and adipocytes. Although most inflammatory adipokines are released by macrophages, adipocytes can also release immunomodulatory adipokines, such as leptin. The objective of this research was to determine if co-incubation of activated macrophages with mature adipocytes, using Transwell inserts, affected leptin release by mature adipocytes. We also examined if there were differences in the amount of cell-secreted products quantified in cell-conditioned media collected from macrophage-containing (Transwell insert) and adipocyte-containing (well) compartments. Mature adipocytes (differentiated 3T3-L1 murine fibroblasts) were co-incubated with control and lipopolysaccharide-stimulated (0.01 μg/ml) murine macrophages (RAW264.7), and nitric oxide, interleukin-6, and leptin levels were quantified in the cell-conditioned media from the two compartments. Activation status of the macrophages did not affect leptin release by the adipocytes. We observed higher amounts of leptin in wells compared to Transwells. Nitric oxide and interleukin-6 levels were similar between Transwells and wells, suggesting that these adipokines are traveling through the Transwell inserts and reaching equilibrium between the two compartments. There was a weak negative relationship between nitric oxide release by macrophages and leptin release by adipocytes. Our results suggest that co-incubating activated macrophages and adipocytes using Transwell inserts can result in distinct microenvironments in the different cellular compartments and that separate sampling of these compartments is required to detect the subtle signaling dynamics that exist between these cells.
Parallel Implementation of Smith-Waterman Algorithm on FPGA
Authors: de Oliveira Fabio F. , Dias Leonardo A. , Fernandes Marcelo A. C. 
Published: July 2021

AbstractIn bioinformatics, alignment is an essential technique for finding similarities between biological sequences. Usually, the alignment is performed with the Smith-Waterman (SW) algorithm, a well-known sequence alignment technique of high-level precision based on dynamic programming. However, given the massive data volume in biological databases and their continuous exponential increase, high-speed data processing is necessary. Therefore, this work proposes a parallel hardware design for the SW algorithm with a systolic array structure to accelerate the Forward and Backtracking steps. For this purpose, the architecture calculates and stores the paths in the Forward stage for pre-organizing the alignment, which reduces the complexity of the Backtracking stage. The backtracking starts from the maximum score position in the matrix and generates the optimal SW sequence alignment path. The architecture was validated on Field-Programmable Gate Array (FPGA), and synthesis analyses have shown that the proposed design reaches up to 79.5 Giga Cell Updates per Second (GCPUS).
Met-HER3 crosstalk supports proliferation via MPZL3 in MET-amplified cancer cells
Authors: Stern Yaakov E. , Duhamel Stephanie , Al-Ghabkari Abdulhameed , Monast Anie , Fiset Benoit , Aboualizadeh Farzaneh , Yao Zhong , Stagljar Igor , Walsh Logan A. , Park Morag 
Published: July 2021

ABSTRACTReceptor tyrosine kinases (RTKs) are recognized as targets of precision medicine in human cancer upon their gene amplification or constitutive activation, resulting in increased downstream signal complexity including heterotypic crosstalk with other RTKs. The Met RTK exhibits such reciprocal crosstalk with several members of the human EGFR (HER) family of RTKs when amplified in cancer cells. We show that Met signaling converges on HER3 tyrosine phosphorylation across a panel of seven MET-amplified cancer cell lines and that HER3 is required for cancer cell expansion and oncogenic capacity in-vitro and in-vivo. Gene expression analysis of HER3-depleted cells identified MPZL3, encoding a single-pass transmembrane protein, as a HER3-dependent effector in multiple MET-amplified cancer cell lines. MPZL3 interacts with HER3 and MPZL3 loss phenocopies HER3 loss in MET-amplified cells, while MPZL3 overexpression rescues proliferation upon HER3 depletion. Together, these data support an oncogenic role for a HER3-MPZL3 axis in MET-amplified cancers.
ACTION AFFORDANCE AFFECTS PROXIMAL AND DISTAL GOAL-ORIENTED PLANNING
Authors: Keshava Ashima , Gottschewsky Nina , Balle Stefan , Nezami Farbod Nosrat , Schüler Thomas , König Peter 
Published: July 2021

AbstractSeminal studies on human cognitive behavior have been conducted in controlled laboratory settings, demonstrating that visual attention is mainly goal-directed and allocated based on the action performed. However, it is unclear how far these results generalize to cognition in more naturalistic settings. The present study investigates active inference processes revealed by eye movements during interaction with familiar and novel tools with two levels of realism of the action affordance. We presented participants with 3D tool models that were either familiar or unfamiliar, oriented congruent or incongruent to their handedness, and asked participants to interact with them by lifting or using. Importantly, we used the same experimental design in two setups. In the first experiment, participants interacted with a VR controller in a low realism environment; in the second, they performed the task with an interaction setup that allowed differentiated hand and finger movements in a high realism environment. We investigated the differences in odds of fixations and their eccentricity towards the tool parts before action initiation. The results show that participants fixate more on the tool’s effector part before action initiation for the use task for unfamiliar tools. Furthermore, with more realistic action affordances, subjects fixate more on the tool’s handle as a function of the tool’s orientation, well before the action was executed. Secondly, the spatial viewing bias on the tool reveals early fixations are influenced by the task and the familiarity of the tools. In contrast, later fixations are associated with the manual planning of the interaction. In sum, the findings from the experiments suggest that fixations are made in a task-oriented way to plan the intended action well before action initiation. Further, with more realistic action affordances, fixations are made towards the proximal goal of optimally planning the grasp even though the perceived action on the tools is identical for both experimental setups. Taken together, proximal and distal goal-oriented planning is contextualized to the realism of action/interaction afforded by an environment.
ANTH domains within CALM, HIP1R, and Sla2 recognize ubiquitin internalization signals
Authors: Pashkova Natalya , Gakhar Lokesh , Yu Liping , Schnicker Nicholas J. , Minard Annabel Y. , Winistorfer Stanley , Johnson Ivan E. , Piper Robert C. 
Published: July 2021

AbstractUbiquitin (Ub) serves as a signal for clathrin-mediated endocytosis (CME) by engaging Ub-binding proteins with the internalization apparatus. Ub is a versatile internalization signal because it can be added to a wide variety of membrane proteins, expanding the capacity of cells to use a variety of regulatory mechanisms to specify the conditions under which a particular protein will be internalized. Several candidate adaptors that can recognize ubiquitinated membrane proteins have been identified that work in endocytic processes that are both clathrin-dependent and independent. These include Epsin and Eps15, which bind and help sort Ub-cargo into internalization sites. Here we identify additional components of the endocytosis apparatus that bind Ub. The N-terminal ANTH domains found in CALM, AP180, HIP1R and yeast Sla2 all bind monoubiquitin with µM affinity. ANTH domains belong to a larger superfamily of domains including ENTH and VHS domains, many of which have Ub-binding regions outside of their VHS/ENTH/ANTH domains that enable them to mediate Ub-dependent sorting events throughout the cell. Solution NMR studies combined with a crystal structure of the CALM ANTH domain in a complex with Ub show that Ub binds to a C-terminal region of the ANTH domain that is not present in ENTH domains. Combined loss of Ub-binding by ANTH-domain proteins and other Ub-binding domains within the internalization apparatus of yeast caused defects in the Ub-dependent internalization of the GPCR Ste2 but had no effect on internalization of Ste2 via other internalization signals. These studies define new components of the internalization machinery that work collectively with Epsin and Eps15 to specify recognition of Ub as an internalization signal.
Phosphate starvation response precedes abscisic acid response under progressive mild drought in plants
Authors: Nagatoshi Yukari , Ikazaki Kenta , Kobayashi Yasufumi , Mizuno Nobuyuki , Sugita Ryohei , Takebayashi Yumiko , Kojima Mikiko , Sakakibara Hitoshi , Kobayashi Natsuko I. , Tanoi Keitaro , Fujii Kenichiro , Baba Junya , Ogiso-Tanaka Eri , Ishimoto Masao , Yasui Yasuo , Oya Tetsuji , Fujita Yasunari 
Published: July 2021

AbstractDrought severely damages crop production, even under conditions so mild that the leaves show no signs of wilting. However, it is unclear how field-grown plants respond to mild drought. Here, we show through 6 years of field trials that ridges are a useful experimental tool to mimic mild drought stress in the field. Mild drought reduces inorganic phosphate levels in the leaves to activate the phosphate starvation response in soybean plants in the field. UsingArabidopsis thalianaand its mutant plants grown in pots under controlled environments, we demonstrate that phosphate starvation response (PSR) occurs before abscisic acid response under progressive mild drought and that PSR plays a crucial role in plant growth under mild drought. Our observations in the field and laboratory using model crop and experimental plants provide insight into the molecular response to mild drought in field-grown plants and the relationship between nutrition and drought stress response.
Upregulation of breathing rate during running exercise by central locomotor circuits
Authors: Hérent Coralie , Diem Séverine , Fortin Gilles , Bouvier Julien 
Published: July 2021

AbstractWhile respiratory adaptation to exercise is compulsory to cope with the increased metabolic supply to body tissues and with the necessary clearing of metabolic waste, the neural apparatus at stake remains poorly identified. Using viral tracing, ex vivo and in vivo optogenetic and chemogenetic interference strategies in mice, we unravel interactive locomotor and respiratory networks’ nodes that mediate the respiratory rate increase that accompanies a running exercise. We show that the mesencephalic locomotor region (MLR) and the lumbar spinal locomotor pattern generator (lumbar CPG), which respectively initiate and execute the locomotor behavior, access the respiratory network through distinct entry points. The MLR directly projects onto the inspiratory rhythm generator, the preBötzinger complex (preBötC), and can trigger a moderate increase of respiratory frequency, prior to, or even in the absence of, locomotion. In contrast, the lumbar CPG projects onto the retrotrapezoid nucleus (RTN) that in turn contacts the preBötC to enforce, during effective locomotion, higher respiratory frequencies. These data expand, on the one hand, the functional implications of the MLR beyond locomotor initiation to a bona fide respiratory modulation. On the other hand, they expand the adaptive respiratory ambitions of the RTN beyond chemoception to “locomotor- ception”.
Data and model considerations for estimating time-varying functional connectivity in fMRI
Authors: Ahrends C , Stevner A , Pervaiz U , Kringelbach ML , Vuust P , Woolrich M , Vidaurre D 
Published: July 2021

AbstractFunctional connectivity (FC) in the brain has been shown to exhibit subtle but reliable modulations within a session. One way of estimating time-varying FC is by using state-based models that describe fMRI time series as temporal sequences of states, each with an associated, characteristic pattern of FC. However, the estimation of these models from data sometimes fails to capture changes in a meaningful way, such that the model estimation assigns entire sessions (or the largest part of them) to a single state, therefore failing to capture within-session state modulations effectively; we refer to this phenomenon as the model becoming static, or model stasis. Here, we aim to quantify how the nature of the data and the choice of model parameters affect the model’s ability to detect temporal changes in FC using both simulated fMRI time courses and resting state fMRI data. We show that large between-subject FC differences can overwhelm subtler within-session modulations, causing the model to become static. Further, the choice of parcellation can also affect the model’s ability to detect temporal changes. We finally show that the model often becomes static when the number of free parameters that need to be estimated is high and the number of observations available for this estimation is low in comparison. Based on these findings, we derive a set of practical recommendations for time-varying FC studies, in terms of preprocessing, parcellation and complexity of the model.HighlightsTime-varying FC models sometimes fail to detect temporal changes in fMRI dataBetween- and within-subject FC variability affect model stasisThe choice of parcellation affects model stasis in real fMRI dataThe number of observations and free parameters critically affect model stasis Keywords: fMRI; time-varying FC; Hidden Markov Model (HMM); resting state
SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance
Authors: Kimura Izumi , Kosugi Yusuke , Wu Jiaqi , Yamasoba Daichi , Butlertanaka Erika P , Tanaka Yuri L , Liu Yafei , Shirakawa Kotaro , Kazuma Yasuhiro , Nomura Ryosuke , Horisawa Yoshihito , Tokunaga Kenzo , Takaori-Kondo Akifumi , Arase Hisashi ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Saito Akatsuki , Nakagawa So , Sato Kei 
Published: July 2021

SummarySARS-CoV-2 Lambda, a new variant of interest, is now spreading in some South American countries; however, its virological features and evolutionary trait remain unknown. Here we reveal that the spike protein of the Lambda variant is more infectious and it is attributed to the T76I and L452Q mutations. The RSYLTPGD246-253N mutation, a unique 7-amino-acid deletion mutation in the N-terminal domain of the Lambda spike protein, is responsible for evasion from neutralizing antibodies. Since the Lambda variant has dominantly spread according to the increasing frequency of the isolates harboring the RSYLTPGD246-253N mutation, our data suggest that the insertion of the RSYLTPGD246-253N mutation is closely associated with the massive infection spread of the Lambda variant in South America.HighlightsLambda S is highly infectious and T76I and L452Q are responsible for this propertyLambda S is more susceptible to an infection-enhancing antibodyRSYLTPGD246-253N, L452Q and F490S confer resistance to antiviral immunityGraphical Abstract
Unearthing Shifts in Microbial Communities Across a Soil Disturbance Gradient
Authors: Seitz Taylor J. , Schütte Ursel M. E. , Drown Devin M. 
Published: July 2021

AbstractPermafrost, an important source of soil disturbance, is particularly vulnerable to climate change in Alaska where 85% of the land is underlain with discontinuous permafrost. Boreal forests, home to plants integral to subsistence diets of many Alaska Native communities, are not immune to the effects of climate change. Soil disturbance events such as permafrost thaw, wildfires, and land use change can influence abiotic conditions which can then affect active layer soil microbial communities. Previously, we found negative effects on boreal plants inoculated with microbes impacted by soil disturbance compared to plants inoculated with microbes from undisturbed soils. Here, we identify the key shifts in microbial inoculant communities altered by soil disturbance using 16S rRNA amplicon sequencing as well as changes in potential functional mechanisms that influence plant growth using long read metagenomics. Across our soil disturbance gradient, microbial communities differ significantly based on the level of soil disturbance. Consistent with previous results, the family Acidobacteriaceae, which consists of known plant promoters, was abundant in undisturbed soil, but practically absent in most disturbed soil. In contrast, Comamonadaceae, a family with known agricultural pathogens, was overrepresented in most disturbed soil communities compared to undisturbed. Within our metagenomic data, we found that soil disturbance level drives differences in microbial community function. These results indicate that a decrease in plant growth can be linked to changes in the community and functional composition driven by soil disturbance and climate change. Together these results build a genomic understanding of how shifting soil microbiomes may affect plant productivity and ecosystem health as the Arctic warms.
SARS-CoV-2 in the Republic of Guinea: Fragment and Whole-Genome Sequencing, Phylogenetic Analysis
Authors: Kritsky A.A. , Krasnov Ya.M. , Keita M. , Keita S. , Fedorov A.V. , Shevtsova A.P. , Guseva N.P. , Kazorina E.V. , Sosedova E.A. , Katyshev A.D. , Naryshkina E.A. , Kolomoets E.V. , Shcherbakova S.A. , Popova A.Yu. , Kutyrev V.V. 
Published: July 2021

AbstractGenetic diversity of SARS-CoV-2 isolates circulating in the Republic of Guinea in May and June 2020, as well as in March 2021, has been demonstrated using fragment (S gene) and whole genome sequencing of 14 strains. Analysis of nucleotide sequences and phylogenetic constructs make it possible to divide the studied strains into 3 groups. Comparison of the obtained data with the already available epidemiological data proves the initial importation of COVID-19 from Western European countries, and also demonstrates four independent import routes in two time periods (March 2020 and no later than March 2021).
T helper cell-licensed mast cells promote inflammatory Th17 cells
Authors: Leveque Edouard , Joulia Régis , Petitfils Camille , Mas-Orea Xavier , Payros Gaelle , Laurent Camille , Gaudenzio Nicolas , Dietrich Gilles , Valitutti Salvatore , Cenac Nicolas , Espinosa Eric 
Published: July 2021

SummaryCD4+ T helper cells (Th) infiltrate sites of inflammation and orchestrate the immune response by instructing local leukocytes. Mast cells (MCs) are tissue sentinel cells particularly abundant in skin and mucosa. Here, we analyzed the interplay between human MCs and Th cells and, through the application of RNAseq and functional assays, showed that Th cells induced a specific transcriptomic program in helped MCs (named here MCTH) driving them toward an inflammatory phenotype. The gene signature of MCTH indicated that MCs helped by Th cell acquired in turn the capacity to regulate effector T cell response through wide-range of soluble and membrane ligands. Accordingly, we showed that MCTH promoted Th17 cells and notably an inflammatory subset of Th17, producing both IFN-γ and GM-CSF, through a PGE2 and IL-1β axis. Our findings demonstrate that activated effector/memory CD4+ T cells activate and instruct resting MCs toward a specific differentiated pro-inflammatory phenotype endowed with the capacity to speak back to effector T cells and to mold their functions.
Navigating a diversity of turbulent plumes is enhanced by sensing complementary temporal features of odor signals
Authors: Jayaram Viraaj , Kadakia Nirag , Emonet Thierry 
Published: July 2021

AbstractWe and others have shown that during odor plume navigation, walking Drosophila melanogaster bias their motion upwind in response to both the frequency of their encounters with the odor (Demir et al., 2020), and the intermittency of the odor signal, i.e. the fraction of time the signal is above a detection threshold (Alvarez-Salvado et al., 2018). Here we combine and simplify previous mathematical models that recapitulated these data to investigate the benefits of sensing both of these temporal features, and how these benefits depend on the spatiotemporal statistics of the odor plume. Through agent-based simulations, we find that navigators that only use frequency or intermittency perform well in some environments – achieving maximal performance when gains are near those inferred from experiment – but fail in others. Robust performance across diverse environments requires both temporal modalities. However, we also find a steep tradeoff when using both sensors simultaneously, suggesting a strong benefit to modulating how much each sensor is weighted, rather than using both in a fixed combination across plumes.
Filopodia powered by class X myosin promote fusion of mammalian myoblasts
Authors: Hammers David W. , Hart Cora C. , Matheny Michael K. , Heimsath Ernest G. , Lee Young il , Hammer John A. , Cheney Richard E. , Sweeney H. Lee 
Published: July 2021

ABSTRACTSkeletal muscle fibers are multinucleated cellular giants formed by the fusion of mononuclear myoblasts. Several molecules involved in myoblast fusion have been discovered, and finger-like projections coincident with myoblast fusion have also been implicated in the fusion process. The role of these cellular projections in muscle cell fusion was investigated herein. We demonstrate that these projections are filopodia generated by class X myosin (Myo10), an unconventional myosin motor protein specialized for filopodia. We further show that Myo10 is highly expressed by differentiating myoblasts, and Myo10 ablation inhibits both filopodia formation and myoblast fusion in vitro. In vivo, Myo10 labels regenerating muscle fibers associated with Duchenne muscular dystrophy and acute muscle injury. Conditional loss of Myo10 from muscle-resident stem cells, known as satellite cells, severely impairs postnatal muscle regeneration. Furthermore, the muscle fusion proteins Myomaker and Myomixer are detected in myoblast filopodia. These data demonstrate that Myo10-driven filopodia facilitate multi-nucleated mammalian muscle formation.