bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hierarchical unimodal processing within the primary somatosensory cortex during a bimodal detection task
Authors: Parra Sergio , Diaz Héctor , Zainos Antonio , Alvarez Manuel , Zizumbo Jerónimo , Pujalte Sebastián , Bayones Lucas , Romo Ranulfo , Rossi-Pool Román 
Published: August 2022

Where and how in the brain do neurons process more than one sensory modality? To answer these questions, scientists have generated a wide variety of studies at distinct space-time scales in different animal models, and often shown contradictory conclusions. Some conclude that this process occurs in early sensory cortices, but others that this occurs in areas central to sensory cortices. Here, we sought to determine whether sensory neurons process and encode physical stimulus properties of different modalities (tactile and acoustic). For this, we designed a bimodal detection task where the senses of touch and hearing compete from trial to trial. Two Rhesus monkeys performed this novel task, while neural activity was recorded in areas 3b and 1 of the primary somatosensory cortex (S1). We analyzed neurons’ coding properties and variability, organizing them by their receptive field’s position relative to the stimulation zone. Our results indicate that neurons of areas 3b and 1 are unimodal, encoding only the tactile modality, both in the firing rate and variability, but not to the acoustic one. Moreover, we found that neurons of both subareas encode the tactile information differently, revealing a hidden processingbased hierarchy. Finally, using a powerful non-linear dimensionality reduction algorithm, we show that the activity from areas 3b and 1 can be separated, establishing a clear division in the functionality of these two subareas of S1.SIGNIFICANCE STATEMENTOur brain integrates information from all our senses to perceive the external world. But where and how in the brain this integration occurs? Here we ask if the primary somatosensory cortex (S1) encodes information from more than one sensory modality. We recorded the activity of single neurons from areas 3b and S1, while trained monkeys performed a bimodal detection task, where tactile and acoustic stimuli compete. The analysis showed that neurons from areas 3b and 1 responded only to the tactile modality both in their rate and variability. However, our results support that these two areas are different enough as to be considered functionally distinct entities.
Maximum tree lifespans derived from public-domain dendrochronological data
Authors: Biondi Franco , Meko David , Piovesan Gianluca 
Published: August 2022

AbstractThe public-domain International Tree-Ring Data Bank (ITRDB) is an under-utilized dataset to improve existing estimates of global tree longevity. Since dendrochronologists have usually targeted the oldest trees in a stand, this public-domain resource is bound to offer better estimates of maximum tree age than those available from randomized plots or grid-based forest inventories. We used the longest continuous ring-width series of existing ITRDB collections as an index of maximum tree age for that species and site. Using a total of 3679 collections, we obtained longevity estimates for 236 unique tree species, 156 conifers and 80 angiosperms, distributed all over the world. More than half of the species (167) were represented by no more than 10 collections, and a similar number of species (144) reached longevity greater than 300 years. Maximum tree ages exceeded 1000 years for several species (22), all of them conifers, while angiosperm longevity peaked around 500 years. As new collections are constantly being added to the ITRDB, estimates of tree longevity may change slightly, mainly by adding new species to the database. Given the current emphasis on identifying human-induced impacts on global systems, detailed analyses of ITRDB holdings provide one of the most reliable sources of information for tree longevity as an ecological trait.Key MessageBaseline information on tree longevity was derived from the most extensive dendrochronological database currently available. The resulting summary provides a reference point, to be used for modeling and research purposes.
RaPiD-chamber: Easy to self-assemble live-imaging chamber with adjustable LEDs allows to track small differences in dynamic plant movement adaptation on tissue level
Authors: Kashkan Ivan , García-González Judith , Lacek Jozef , Müller Karel , Růžička Kamil , Retzer Katarzyna , Weckwerth Wolfram 
Published: August 2022

AbstractPlants rely on fine-tuning organ movement to ensure their survival and productivity. Even subtle loss of directional growth orchestration can result in a huge impact when the plant is impaired to adapt to an ever-changing environment, where it is exposed to manifold exogenous stimuli simultaneously. We present a newly designed chamber to obtain live images to track organ growth and movement differences, called RaspberyPi Dark Chambers (RaPiD-chamber). The RaPiD-chamber is easy to self-assemble and cost-efficient and allows to monitor the continuous growth of etiolated seedlings, as well as their response to light of different wavelengths and from chosen positions. We tested the advice by comparing hypocotyl elongation rate and response to unilateral white and blue light exposure of Arabidopsis thaliana Col0. Additionally, we compared the elongation rate of etiolated hypocotyls between Col0 and kin10, a mutant lacking the catalytic subunit of the cellular signaling hub SUCROSE NON-FERMENTING RELATED KINASE 1 (SnRK1). kin10 is known for its diminished ability to control hypocotyl elongation. As a case study, we compared the growth dynamics of etiolated Col0 versus kin10. Without further energy source supplementation to the growth medium, the mutant cannot keep up with hypocotyl elongation. Additionally, continuous observation of the dark-grown seedlings allowed us to determine a shift in the dynamics of apical hook angle formation for the mutant.
pYtags enable spatiotemporal measurements of receptor tyrosine kinase signaling in living cells
Authors: Farahani Payam E. , Yang Xiaoyu , Mesev Emily V. , Fomby Kaylan A. , Bashor Caleb J. , Nelson Celeste M. , Toettcher Jared E. 
Published: August 2022

AbstractReceptor tyrosine kinases (RTKs) are major signaling hubs in metazoans, playing crucial roles in cell proliferation, migration, and differentiation. However, few tools are available to measure the activity of a specific RTK in individual living cells. Here, we present pYtags, a modular approach for monitoring the activity of a user-defined RTK by live-cell microscopy. pYtags consist of an RTK modified with a tyrosine activation motif that, when phosphorylated, recruits a fluorescently labeled tandem SH2 domain with high specificity. We show that pYtags enable the monitoring of a specific RTK on seconds-to-minutes time scales and across subcellular and multicellular length scales. Using a pYtag biosensor for epidermal growth factor receptor (EGFR), we quantitively characterize how signaling dynamics vary with the identity and dose of activating ligand. We show that orthogonal pYtags can be used to monitor the dynamics of EGFR and ErbB2 activity in the same cell, revealing distinct phases of activation for each RTK. The specificity and modularity of pYtags opens the door to robust biosensors of multiple tyrosine kinases and may enable engineering of synthetic receptors with orthogonal response programs.HighlightspYtags report on signaling of user-defined RTKs in living cellsEGFR signaling dynamics depend on ligand identity and dimer strengthrthogonal pYtags enable reporter multiplexingpYtags can report on signaling of endogenously expressed RTKs
Urotensin II-Related Peptides, Urp1 and Urp2, Control Zebrafish Spine Morphology
Authors: Bearce Elizabeth A. , Irons Zoe H. , O’Hara-Smith Johnathan R. , Kuhns Colin J. , Fisher Sophie I. , Crow William E. , Grimes Daniel T. 
Published: August 2022

ABSTRACTThe spine provides structure and support to the body, yet how it develops its characteristic morphology as the organism grows is little understood. This is underscored by the commonality of conditions in which the spine curves abnormally such as scoliosis, kyphosis and lordosis. Understanding the origin of such spinal curves has been challenging in part due to the lack of appropriate animal models. Recently, zebrafish have emerged as promising tools with which to understand the origin of spinal curves. Using zebrafish, we demonstrate that the Urotensin II-related peptides (URPs), Urp1 and Urp2, are essential for maintaining spine morphology. Urp1 and Urp2 are 10-amino acid cyclic peptides expressed by neurons lining the central canal of the spinal cord. Upon combined genetic loss of Urp1 and Urp2, adolescent-onset planar curves manifested in the caudal region of the spine, akin to a lordosis-like condition. Highly similar curves were caused by mutation of Uts2r3, an URP receptor. Quantitative comparisons revealed that Urotensin-associated curves were distinct from other zebrafish spinal curve mutants that more closely reflected idiopathic scoliosis or kyphosis. Last, we found that the Reissner fiber, a proteinaceous thread that sits in the central canal and has been implicated in the control of spine morphology, breaks down prior to curve formation in an idiopathic scoliosis model but was unperturbed by loss of Uts2r3. This suggests a Reissner fiber-independent mechanism of curvature in Urotensin-deficient mutants. Overall, our results show that Urp1 and Urp2 control zebrafish spine morphology and establish new animal models of lordosis-like curves.
DNARecords: An extensible sparse format for petabyte scale genomics analysis
Authors: Manas Andres , Seninge Lucas , Dixit Atray 
Published: August 2022

AbstractRecent growth in population scale sequencing initiatives involve both cohort scale and proportion of genome surveyed, with a transition from genotyping arrays to broader genome sequencing approaches. The resulting datasets can be challenging to analyze. Here we introduce DNARecords a novel sparse-compatible format for large scale genetic data. The structure enables integration of complex data types such as medical images and drug structures towards the development of machine learning methods to predict disease risk and drug response. We demonstrate its speed and memory advantages for various genetics analyses. These performance advantages will become more pronounced as it becomes feasible to analyze variants of lower population allele frequencies. Finally, we provide an open-source software plugin, built on top of Hail, to allow researchers to write and read such records as well as a set of examples for how to use them.
Tissue-Like 3D Standard and Protocols for Microscope Quality Management
Authors: Abrams Benjamin , Pengo Thomas , Wee Tse-Luen , Deagle Rebecca C. , Vuillemin Nelly , Callahan Linda M. , Smith Megan A. , Kubow Kristopher E. , Girard Anne-Marie , Rappoport Joshua Z. , Bayles Carol J. , Cameron Lisa A. , Cole Richard , Brown Claire M. 
Published: August 2022

ABSTRACTThis article outlines a global study conducted by the Association of Biomedical Resource Facilities (ABRF) Light Microscopy Research Group (LMRG). The results present a novel 3D tissue-like biologically relevant standard sample that is affordable and straightforward to prepare. Detailed sample preparation and instrument specific image acquisition protocols and image analysis methods are presented and made available to the community. The standard consists of sub-resolution and large well characterized relative intensity fluorescence microspheres embedded in a 120 µm thick 3D gel with a refractive index of 1.365. The standard allows the evaluation of several properties as a function of depth. These include: 1) microscope resolution with automated analysis of the point spread function (PSF), 2) automated signal-to-noise- ratio analysis, 3) calibration and correction of fluorescence intensity loss, and 4) quantitative relative intensity. Results demonstrate expected refractive index mismatch dependent losses in intensity and resolution with depth but the relative intensities of different objects at similar depths were maintained. This is a robust standard showing reproducible results across laboratories, microscope manufacturers and objective lens types (e.g. magnification, immersion medium). Thus, these tools will be valuable for the global community to benchmark fluorescence microscopes and will contribute to improved rigor and reproducibility.
The Interactions of Potassium Hydroxide in the Vicinity of Connective Disulfide Bonds of the Fab Regions of Some Human Immunoglubulins: Preliminary Computational Implications for Affinity on Cys-Cys Disulfide Bridges
Authors: Zumrutdal Emin 
Published: August 2022

ABSTRACTThe average human lifespan continues to increase with the increase in data flow and the advancement of related technological developments. However, this development brings with it many diseases, including immunological problems. Immunoglobulin varieties found in different organisms in the last 3-4 decades continue to be hope for many diseases.Interest has focused on the lesser weight but more mobile immunoglobulins found in camelids. Later, different types of these antibodies were tried to be made with biotechnological engineering and their effectiveness continues to be investigated. Disulfide bridges located on the immunoglobulin are one of the key points for the structure and function of the immunoglobulin. The interest of potassium hydroxide in disulfide bridges may enable us to damage or break these bonds. For this purpose, in this study, the relationship between disulfide bridges between light and heavy chains and potassium hydroxide was investigated. It was observed that the affinity of potassium hydroxide to disulfide bridges occurred exergonically. In the light of this information, it can be thought that lighter, more functional immunoglobulin fragments and nanobodies can be formed with potassium hydroxide compared to conventional immunoglobulin.
ENVIROME-WIDE ASSOCIATIONS ENHANCE MULTI-YEAR GENOME-BASED PREDICTION OF HISTORICAL WHEAT BREEDING DATA
Authors: Costa-Neto Germano , Crespo-Herrera Leonardo , Fradgley Nick , Gardner Keith , Bentley Alison R. , Dreisigacker Susanne , Fritsche-Neto Roberto , Montesinos-López Osval A. , Crossa Jose 
Published: August 2022

ABSTRACTLinking high-throughput environmental data (enviromics) into genomic prediction (GP) is a cost-effective strategy for increasing selection intensity under genotype-by-environment interactions (G×E). This study developed a data-driven approach based on Environment-Phenotype Associations (EPA) aimed at recycling important G×E information from historical breeding data. EPA was developed in two applications: (1) scanning a secondary source of genetic variation, weighted from the shared reaction-norms of past-evaluated genotypes; (2) pinpointing weights of the similarity among trial-sites (locations), given the historical impact of each envirotyping data variable for a given site. Then, the EPA outcomes were integrated into multi-environment GP models through a new single-step GBLUP. The wheat trial data used included 36 locations, 8 years and 3 target populations of environments (TPE) in India. Four prediction scenarios and 6 kernel-models within/across TPEs were tested. Our results suggest that the conventional GBLUP, without enviromic data or when omitting EPA, is inefficient in predicting the performance of wheat lines in future years. However, when EPA was introduced as an intermediary learning step to reduce the dimensionality of the G×E kernels while connecting phenotypic and environmental-wide variation, a significant enhancement of G×E prediction accuracy was evident. EPA revealed that the effect of seasonality makes strategies such as “covariable selection” unfeasible because G×E is year-germplasm specific. We propose that the EPA effectively serves as a “reinforcement learner” algorithm capable of uncovering the effect of seasonality over the reaction-norms, with the benefits of better forecasting the similarities between past and future trialing sites. EPA combines the benefits of dimensionality reduction while reducing the uncertainty of genotype-by-year predictions and increasing the resolution of GP for the genotype-specific level.
Amodal population clock in the primate medial premotor system for rhythmic tapping
Authors: Betancourt Abraham , Pérez Oswaldo , Gámez Jorge , Mendoza Germán , Merchant Hugo 
Published: August 2022

AbstractThe neural substrate for beat extraction and response entrainment to auditory and visual rhythms is still unknown. Here we analyzed the population activity of hundreds of medial premotor neurons of monkeys performing an isochronous tapping guided by brief flashing stimuli or auditory tones. The animals showed a strong bias towards visual than auditory metronomes, with rhythmic tapping that was more precise and accurate on the former. The population dynamics shared the following properties across modalities: the circular dynamics of the neural trajectories formed a regenerating loop for every produced interval; the trajectories converged in similar state space at tapping times resetting the clock; the tempo of the synchronized tapping was encoded in the trajectories by a combination of amplitude modulation and temporal scaling. In addition, the modality induced a displacement in the neural trajectories in auditory and visual subspaces without greatly altering time keeping mechanism. These results suggest that the interaction between the MPC amodal internal representation of pulse and a modality specific external input generates a neural rhythmic clock whose dynamics governs rhythmic tapping execution across senses.
Plasticity and lineage commitment of individual Th1 cells are determined by stable T-bet expression quantities
Authors: Hegazy Ahmed N. , Peine Caroline , Niesen Dominik , Panse Isabel , Vainshtein Yevhen , Kommer Christoph , Zhang Qin , Brunner Tobias M. , Peine Michael , Fröhlich Anja , Ishaque Naveed , Marek Roman M. , Zhu Jinfang , Höfer Thomas , Löhning Max 
Published: August 2022

SUMMARYT helper 1 (Th1) cell identity is defined by the expression of the lineage-defining transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinctin vivo-differentiated Th1 cells based on their quantitative expression of T-bet and interferon-γ. Heterogeneous T-bet expression states were regulated by virus-induced type-I interferons and were stably maintained even after secondary viral infection. Exposed to Th2-polarizing conditions, the sorted subpopulations exhibited graded levels of plasticity: T-bet quantities were inversely correlated with the ability to express the Th2 lineage-specifying transcription factor GATA-3 and Th2 cytokines. Reprogramed Th1 cells acquired graded, but stable mixed Th1+2 phenotypes with a hybrid epigenetic landscape. Continuous presence of T-bet in differentiated Th1 cells was essential to ensure Th1 cell stability. Thus, innate cytokine signals regulate Th1 cell plasticity via an individual cell-intrinsic rheostat to enable T cell subset adaptation to subsequent challenges.HIGHLIGHTSType-I interferons triggered by infection determine T-bet expression states in Th1 cellsT-bet and IFN-γ expression states indicate the plasticity of individual Th1 cellsIndividual T-bet expression states and plasticity persist after secondary infectionReprogramming yields stable Th1+2 phenotypes and a mixed epigenetic landscape
Evasion of Neutralizing Antibody Response by the SARS-CoV-2 BA.2.75 Variant
Authors: Qu Panke , Evans John P. , Zheng Yi-Min , Carlin Claire , Saif Linda J. , Oltz Eugene M. , Xu Kai , Gumina Richard J. , Liu Shan-Lu 
Published: August 2022

AbstractThe newly emerged BA.2.75 SARS-CoV-2 variant exhibits an alarming 9 additional mutations in its spike (S) protein compared to the ancestral BA.2 variant. Here we examine the neutralizing antibody escape of BA.2.75 in mRNA-vaccinated and BA.1-infected individuals, as well as the molecular basis underlying functional changes in the S protein. Notably, BA.2.75 exhibits enhanced neutralization resistance over BA.2, but less than the BA.4/5 variant. The G446S and N460K mutations of BA.2.75 are primarily responsible for its enhanced resistance to neutralizing antibodies. The R493Q mutation, a reversion to the prototype sequence, reduces BA.2.75 neutralization resistance. The mutational impact is consistent with their locations in common neutralizing antibody epitopes. Further, the BA.2.75 variant shows enhanced cell-cell fusion over BA.2, driven largely by the N460K mutation, which enhances S processing. Structural modeling revealed a new receptor contact introduced by N460K, supporting a mechanism of potentiated receptor utilization and syncytia formation.
Unconventional Initiation of PINK1/Parkin Mitophagy by Optineurin
Authors: Nguyen Thanh Ngoc , Sawa-Makarska Justyna , Khuu Grace , Lam Wai Kit , Adriaenssens Elias , Fracchiolla Dorotea , Shoebridge Stephen , Padman Benjamin Scott , Skulsuppaisarn Marvin , Lindblom Runa S.J. , Martens Sascha , Lazarou Michael 
Published: August 2022

AbstractCargo sequestration is a fundamental step of selective autophagy in which cells generate a double membrane structure termed an autophagosome on the surface of cargoes. NDP52, TAX1BP1 and p62 bind FIP200 which recruits the ULK1/2 complex to initiate autophagosome formation on cargoes. How OPTN initiates autophagosome formation during selective autophagy remains unknown despite its importance in neurodegeneration. Here, we uncover an unconventional path of PINK1/Parkin mitophagy initiation by OPTN that does not begin with FIP200 binding nor require the ULK1/2 kinases. Using gene-edited cell lines andin vitroreconstitutions, we show that OPTN utilizes the kinase TBK1 which binds directly to the class III phosphatidylinositol 3-kinase complex I to initiate mitophagy. During NDP52 mitophagy initiation, TBK1 is functionally redundant with ULK1/2, classifying TBK1’s role as a selective autophagy initiating kinase. Overall, this work reveals that OPTN mitophagy initiation is mechanistically distinct and highlights the mechanistic plasticity of selective autophagy pathways.
Multiomics and quantitative modelling disentangle diet, host, and microbiota contributions to the host metabolome
Authors: Zimmermann-Kogadeeva Maria , Bencivenga-Barry Natasha A. , Zimmermann Michael , Bork Peer , Goodman Andrew L. 
Published: August 2022

AbstractDietary nutrients, host metabolism, and gut microbiota activity each influence the host’s metabolic phenotype; however, the interplay between these factors remains poorly understood. We employed tissue-resolved metabolomics in gnotobiotic mice carrying a synthetic human gut microbiota and germfree mice in two dietary conditions to develop an intestinal flux model that quantifies diet, host, and bacterial contributions to the levels of 2,700 intestinal metabolites. While diet was the main factor affecting metabolite profiles, we identified 1,117 potential microbial substrates and products in the gut. By integrating metagenomics and metatranscriptomics data into genome-scale enzymatic networks, we linked 202 potential substrate-product pairs by a single enzymatic reaction. We further identified bacterial species and enzymes that can explain the differential abundance of 13% of the identified microbial products between the mouse groups. This quantitative modelling approach paves the way for controlling an individual’s metabolic phenotype by modulating their gut microbiome composition and diet.