bluuebunny/crossref_metadata_2025_split huggingface dataset:
An abstract categorical decision code in dorsal premotor cortex
Authors: Diaz-deLeon Gabriel , Alvarez Manuel , Bayones Lucas , Zainos Antonio , Zizumbo Jerónimo , Parra Sergio , Pujalte Sebastián , Romo Ranulfo , Rossi-Pool Román , De Lafuente Victor 
Published: August 2022

AbstractThe dorsal premotor cortex (DPC) has classically been associated with a role in preparing and executing the physical motor variables during cognitive tasks. While recent work has provided nuanced insights into this role, here we propose that DPC also participates more actively in decision-making. We recorded neuronal activity in DPC while two trained monkeys performed a vibrotactile categorization task, utilizing two distinct ranges of stimuli values that varied on two physical attributes: vibrotactile frequency and amplitude. We observed a broad heterogeneity across DPC neurons, the majority of which maintained the same response patterns across attributes and ranges, coding in the same periods, mixing temporal and categorical dynamics. The predominant categorical signal was maintained throughout the delay, movement periods and notably during the inter-trial period. Putting the entire population’s data through two dimensionality reduction techniques, we found that imposing the sensory structure yielded pure categorical and temporal representations. Furthermore, projecting the activity of one population over the population axes of the other yielded identical categorical and temporal responses. Finally, we sought to identify functional subpopulations based on the combined activity of all stimuli, neurons, and time points, however we found a continuum of single-unit responses mixing temporal and categorical dynamics. All this points to DPC playing a more decision-related role than previously anticipated.SIGNIFICANCE STATEMENTThe DPC’s role in the somatosensory processing network has been generally limited to movement, but our current results suggest a more abstract function. We recorded DPC’s activity in two monkeys trained in a vibrotactile categorization task of two distinct physical attributes, and found a strong decision signal throughout the population, underpinned by purely temporal signals. Importantly, this abstract decision signal remains during the inter-trial period suggesting a consolidation role. Neurons maintained consistent and significant responses for both attributes, and the entire population activity converged to identical categorical representations, even when cross-projected between two contexts. These results suggest that DPC plays a larger role during decision-making and consolidation, regardless of the stimulus attributes that triggered the decision report.
C4Grasses Employ Distinct Strategies to Acclimate Rubisco Activase to Heat Stress
Authors: Stainbrook Sarah C , Aubuchon Lindsey N , Chen Amanda , Johnson Emily , Si Audrey , Walton Laila , Ahrendt Angela , Strenkert Daniela , Jez Joseph 
Published: August 2022

1AbstractRising temperatures due to the current climate crisis will have devastating impacts on crop performance and resilience in the near future. One key step that limits plant photosynthetic performance under higher temperatures is the activity of the thermolabile enzyme rubisco activase (RCA). RCA is highly conserved in photosynthetic organisms, including C4crops such asZea mays(maize) andSorghum bicolor(sorghum) which are crucial components of global food supply and the bioenergy sector. While rubisco is the most abundant protein on earth and responsible for carbon fixation, RCA is an essential chaperone required to remove inhibitory sugar phosphates from the active site of rubisco to allow for continued CO2fixation. We set out to understand temperature-dependent RCA regulation in four different C4plants, with a focus on the crop plants maize (two cultivars) and sorghum, as well as the model grassSetaria viridis(setaria). Gas exchange measurements confirm that CO2assimilation is indeed limited by Ribulose 1,5-bisphosphate (RuBP) carboxylation in these organisms and at high temperatures. All three species express distinct sets of RCA isoforms and each species alters the isoform and proteoform abundances in response to heat; however, the changes are species-specific. In order to understand how even subtle changes in the molecular environment of the chloroplast stroma affect RCA function during heat acclimation, we examined the regulation of RCA activity directly with respect thermostability, the ratio of ADP to ATP and the concentration of Mg2+ions. As shown previously, the activity of RCA is modulated by a combination of these variables, but surprisingly, how these biochemical environment factors affect RCA function differs vastly between the different C4species, and differences are even apparent between different cultivars within a single species, both with respect to proteoform abundance and regulation. Our results suggest that each grass evolved different parts of the RCA regulation portfolio and we conclude that a successful engineering approach aimed at improving carbon capture in C4 grasses will need to accommodate these individual regulatory mechanisms.
Screening cell-cell communication in spatial transcriptomics via collective optimal transport
Authors: Cang Zixuan , Zhao Yanxiang , Almet Axel A. , Stabell Adam , Ramos Raul , Plikus Maksim , Atwood Scott X. , Nie Qing 
Published: August 2022

AbstractSpatial transcriptomic technologies and spatially annotated single cell RNA-sequencing (scRNA-seq) datasets provide unprecedented opportunities to dissect cell-cell communication (CCC). How to incorporate the spatial information and complex biochemical processes in reconstructing CCC remains a major challenge. Here we present COMMOT to infer CCC in spatial transcriptomics, which accounts for the competition among different ligand and receptor species as well as spatial distances between cells. A novel collective optimal transport method is developed to handle complex molecular interactions and spatial constraints. We introduce downstream analysis tools on spatial directionality of signalings and genes regulated by such signalings using machine learning models. We apply COMMOT to simulation data and eight spatial datasets acquired with five different technologies, showing its effectiveness and robustness in identifying spatial CCC in data with varying spatial resolutions and gene coverages. Finally, COMMOT reveals new CCCs during skin morphogenesis in a case study of human epidermal development. Both the method and the computational package have broad applications in inferring cell-cell interactions within spatial genomics datasets.
Integrity of membrane fluidity and fatty acid environment are necessary for Ebola virus VP40 assembly and release of viral particles
Authors: Amiar Souad , Johnson Kristen A. , Husby Monica L. , Marzi Andrea , Stahelin Robert V. 
Published: August 2022

AbstractPlasma membrane (PM) domains and order phases have been shown to play a key role in the assembly, release, and entry of several lipid-enveloped viruses. In the present study, we provide a mechanistic understanding of the Ebola virus (EBOV) matrix protein VP40 interaction with PM lipids and their effect on VP40 oligomerization, a crucial step for viral assembly and budding. VP40 matrix formation is sufficient to induce changes in the PM fluidity. We demonstrate that the distance between the lipid headgroups, the fatty acid tail saturation and the order between the two leaflets are important factors for the stability of VP40 binding and oligomerization at the PM. Use of FDA-approved drugs (dibucaine, propranolol and trifluoperazine) to fluidize the plasma membrane, destabilizes the viral matrix assembly leading to a reduction in budding efficiency. Lastly, we show that VP40 can tether and cluster lipid vesicles upon protein enrichment at the membrane. This is a new characteristic of the protein, and it opens the door to new avenues of exploration to deepen our understanding of VP40 host interactions and EBOV assembly. Indeed, our findings support a complex assembly mechanism of the EBOV viral matrix that reaches beyond lipid headgroup specificity using ordered PM lipid regions independent of cholesterol.
Neural Decoding of Inferior Colliculus Multiunit Activity for Sound Category identification with temporal correlation and deep learning
Authors: Özcan F. , Alkan A. 
Published: August 2022

ABSTRACTNatural sounds are easily perceived and identified by humans and animals. Despite this, the neural transformations that enable sound perception remain largely unknown. Neuroscientists are drawing important conclusions about neural decoding that may eventually aid research into the design of brain-machine interfaces (BCIs). It is thought that the time-frequency correlation characteristics of sounds may be reflected in auditory assembly responses in the midbrain and that this may play an important role in identification of natural sounds. In our study, natural sounds will be predicted from multi-unit activity (MUA) signals collected in the inferior colliculus. The temporal correlation values of the MUA signals are converted into images. We used two different segment sizes and thus generated four subsets for the classification. Using pre-trained convolutional neural networks (CNNs), features of the images were extracted and the type of sound heard was classified. For this, we applied transfer learning from Alexnet, GoogleNet and Squeezenet CNNs. The classifiers support vector machines (SVM), k-nearest neighbour (KNN), Naive Bayes and Ensemble were used. The accuracy, sensitivity, specificity, precision and F1 score were measured as evaluation parameters. Considering the trials one by one in each, we obtained an accuracy of 85.69% with temporal correlation images over 1000 ms windows. Using all trials and removing noise, the accuracy increased to 100%.
Bacteroides thetaiotaomicron outer membrane vesicles modulate virulence of Shigella flexneri
Authors: Xerri Nicholas L. , Payne Shelley M. 
Published: August 2022

AbstractThe role of the gut microbiota in the pathogenesis of Shigella flexneri remains largely unknown. To understand the impact of the gut microbiota on S. flexneri virulence, we examined the effect of interspecies interactions with Bacteroides thetaiotaomicron (Bt), a prominent member of the gut microbiota, on S. flexneri invasion. When grown in Bt conditioned medium, S. flexneri showed reduced invasion of human epithelial cells. This decrease in invasiveness of S. flexneri resulted from a reduction in the level of S. flexneri’s master virulence regulator VirF. Reduction of VirF corresponded with a decrease in expression of a secondary virulence regulator virB, as well as expression of S. flexneri virulence genes required for invasion, intracellular motility, and spread. Repression of S. flexneri virulence factors by Bt conditioned medium was not caused by either a secreted metabolite or protein, but rather, was due to the presence of Bt outer membrane vesicles (OMVs) in the conditioned medium. The addition of purified Bt OMVs to S. flexneri growth medium recapitulated the inhibitory effects of Bt conditioned medium on invasion, virulence gene expression, and virulence protein levels. Total lipids extracted from either Bt cells or Bt OMVs also recapitulated the effects of Bt condition medium on expression of the S. flexneri virulence factor IpaC, indicating that Bt OMV lipids, rather than a cargo contained in the vesicles, are the active factor responsible for the inhibition of S. flexneri virulence.ImportanceShigella flexneri is the causative agent of bacillary dysentery in humans. Shigella spp. are one of the leading causes of diarrheal morbidity and mortality, especially among children in low and middle-income countries. The rise of antimicrobial resistance combined with the lack of an effective vaccine for Shigella heightens the importance of studies aimed at better understanding previously uncharacterized aspects of Shigella pathogenesis. Here, we show that conditioned growth medium from the commensal bacteria Bacteroides thetaiotaomicron represses the invasion of S. flexneri. This repression is due to the presence of B. thetaiotaomicron outer membrane vesicles. These findings establish a role for interspecies interactions with a prominent member of the gut microbiota in modulating the virulence of S. flexneri and identify a novel function of outer membrane vesicles in interbacterial signaling between members of the gut microbiota and an enteric pathogen.
Effects of diacutaneous fibrolysis in patients with tension-type headache: A randomized controlled trial
Authors: Cabanillas-Barea Sara , Pérez-Guillén Silvia , López-de-Celis Carlos , Rodríguez-Sanz Jacobo , Fanlo-Mazas Pablo , Carrasco-Uribarren Andoni 
Published: August 2022

AbstractBackgroundManual therapy appears to be effective for the relief of tension-type headache (TTH), just as diacutaneous fibrolysis (DF) has shown to be a beneficial technique for the relief of symptoms in other dysfunctions. However, no studies have evaluated the potential beneficial effect of DF in TTH. The aim of this study is to analyze the effect of three sessions of DF in patients with TTH.MethodsRandomized controlled trial in 86 subjects (43 intervention/ 43 control group). The headache frequency, the headache intensity, the pressure pain thresholds (PPTs) at trapeziometacarpal joint, upper trapezius, suboccipital, frontal and temporal muscles, parietal sutures and the cervical mobility were measured at baseline, at the end of the third intervention and one-month after the last intervention.ResultsStatistically significant differences with p values <0.05 were observed between groups in favor of the intervention group in the one-month follow-up in the following variables: headache frequency, headache intensity, flexion, extension, right and left side-bending, right and left rotation, PPTs in left trapeziometacarpal joint, right suboccipital muscle, right and left temporal muscle, left frontal muscle and right and left parietal.ConclusionsDF provides a beneficial effect in reducing headache frequency, relieving pain, and improving cervical mobility in patients with TTH.
Model Evaluation of Secondary Chemistry due to Disinfection of Indoor Air with Germicidal Ultraviolet Lamps
Authors: Peng Zhe , Miller Shelly L. , Jimenez Jose L. 
Published: August 2022

AbstractAir disinfection using Germicidal Ultraviolet light (GUV) has received increasing attention during the COVID-19 pandemic. GUV uses UVC lamps to inactivate microorganisms, but it also initiates photochemistry in air. However, GUV’s indoor-air-quality impact has not been investigated in detail. Here, we model the chemistry initiated by GUV at 254 (“GUV254”) or 222 nm (“GUV222”) in a typical indoor setting for different ventilation levels. Our analysis showed that GUV254, usually installed in the upper room, can significantly photolyze O3, generating OH radicals that oxidize indoor volatile organic compounds (VOCs) into more oxidized VOCs. Secondary organic aerosol (SOA) is also formed as a VOC-oxidation product. GUV254-induced SOA formation is of the order of 0.1-1 μg/m3for the cases studied here. GUV222 (described by some as harmless to humans and thus applicable for the whole room) with the same effective virus-removal rate makes a smaller indoor-air-quality impact at mid-to-high ventilation rates. This is mainly because of the lower UV irradiance needed and also less efficient OH-generating O3photolysis than GUV254. GUV222 has a higher impact than GUV254 under poor ventilation due to a small but significant photochemical production of O3at 222 nm, which does not occur with GUV254.SynopsisGermicidal ultraviolet light initiates indoor oxidation chemistry, potentially forming indoor air pollutants. The amount is not negligible and depends on both the wavelength of light and the ventilation level.
Jagged1 overexpression on T cells induces thymic regulatory T cells leading to thymic involution
Authors: Kritikou Joanna S. , Sánchez-Pascual Irene , Muñoz-Miranda Juan Pedro , Vashist Neha , Wagner Arnika K. , Zhang Xing-Mei , Assarsson Erika , Dominguez-Villar Margarita , Yagita Hideo , Garcia-Cozar Francisco , Riese Peggy , Harris Robert A. , Ljunggren Hans-Gustaf , Chambers Benedict J. 
Published: August 2022

AbstractWe previously described a mouse model, tg66, with a severe defect resulting in diminished thymic size and complete involution by early adulthood. In the current study, we identified overexpression of Jagged1 as a mechanism for the alterations in thymic development in tg66 mice. T cells in the tg66 thymus were skewed towards CD8+T cells, and within the CD4+T cell compartment there was an over-representation of Foxp3+cells. Regulatory Foxp3+T cells (Tregs) isolated from tg66 mice had increased ST2 and CD103 expression. These Tregs could suppress proliferation to the same extent as conventional Tregs. Corroborating these results, tg66 mice were resistant to experimental induction of neuroinflammation in a common animal model for multiple sclerosis (EAE). Using bone marrow chimeras, we recorded a stark reduction in the number of thymocytes and a corresponding increase in Tregs in the thymus of mice receiving tg66 bone marrow. Conversely, through blocking Jagged1, the number of thymocytes was significantly increased, being concomitantly associated with a drop in the frequency of Tregs. We conclude that Tregs may play a role in thymic involution and could explain early thymic involution or loss as it is observed in diseases of thymic atrophy such as Down syndrome.
GATK-gCNV: A Rare Copy Number Variant Discovery Algorithm and Its Application to Exome Sequencing in the UK Biobank
Authors: Babadi Mehrtash , Fu Jack M. , Lee Samuel K. , Smirnov Andrey N. , Gauthier Laura D. , Walker Mark , Benjamin David I. , Karczewski Konrad J. , Wong Isaac , Collins Ryan L. , Sanchis-Juan Alba , Brand Harrison , Banks Eric , Talkowski Michael E. 
Published: August 2022

SUMMARYCopy number variants (CNVs) are major contributors to genetic diversity and disease. To date, exome sequencing (ES) has been generated for millions of individuals in international biobanks, human disease studies, and clinical diagnostic screening. While standardized methods exist for detecting short variants (single nucleotide and insertion/deletion variants) using tools such as the Genome Analysis ToolKit (GATK), technical challenges have confounded similarly uniform large-scale CNV analyses from ES data. Given the profound impact of rare and de novo coding CNVs on genome organization and human disease, the lack of widely-adopted and robustly benchmarked rare CNV discovery tools has presented a barrier to routine exome-wide assessment of this critical class of variation. Here, we introduce GATK-gCNV, a flexible algorithm to discover rare CNVs from genome sequencing read-depth information, which we distribute as an open-source tool packaged in GATK. GATK-gCNV uses a probabilistic model and inference framework that accounts for technical biases while simultaneously predicting CNVs, which enables self-consistency between technical read-depth normalization and variant calling. We benchmarked GATK-gCNV in 7,962 exomes from individuals in quartet families with matched genome sequencing and microarray data. These analyses demonstrated 97% recall of rare (≤1% site frequency) coding CNVs detected by microarrays and 95% recall of rare coding CNVs discovered by genome sequencing at a resolution of more than two exons. We applied GATK-gCNV to generate a reference catalog of rare coding CNVs in 197,306 individuals with ES from the UK Biobank. We observed strong correlations between CNV rates per gene and measures of mutational constraint, as well as rare CNV associations with multiple traits. In summary, GATK-gCNV is a tunable approach for sensitive and specific CNV discovery in ES, which can easily be applied across trait association and clinical screening.
STAT3 restricts prostate cancer metastasis and antiandrogen resistance by controlling LKB1/CREB signaling pathway
Authors: Pencik Jan , Philippe Cecile , Schlederer Michaela , Pecoraro Matteo , Grund-Gröschke Sandra , Li Wen Jess , Tracz Amanda , Heidegger Isabel , Lagger Sabine , Trachtová Karolína , Oberhuber Monika , Heitzer Ellen , Aksoy Osman , Neubauer Heidi A. , Wingelhofer Bettina , Orlova Anna , Witzeneder Nadine , Dillinger Thomas , Redl Elisa , Greiner Georg , D’Andrea David , Östman Johnny R. , Tangermann Simone , Hermanova Ivana , Schäfer Georg , Varady Adam , Horvath Jaqueline , Stoiber Dagmar , Malcolm Timothy I. , Turner Suzanne D. , Parkes Eileen , Hantusch Brigitte , Egger Gerda , Rose-John Stefan , Poli Valeria , Jain Suneil , Armstrong Chris W.D. , Hoermann Gregor , Goffin Vincent , Aberger Fritz , Moriggl Richard , Carracedo Arkaitz , McKinney Cathal , Kennedy Richard D , Klocker Helmut , Speicher Michael R. , Tang Dean G. , Mann Matthias , Moazzami Ali A. , Heery David M. , Hacker Marcus , Kenner Lukas 
Published: August 2022

AbstractProstate cancer (PCa) lethality is driven by its progression to a metastatic castration-resistant state, yet the signaling mechanisms underlying metastatic spread remain unknown. Here we show that STAT3 converges with the LKB1/mTORC1 and CREB to control metastatic disease in PCa mouse models. Unexpectedly, STAT3 was found to be upregulated in diabetic PCa patients undergoing metformin therapy with a concomitant reduction in mTORC1 expression. In preclinical mouse models of PCa, genetic ablation or activation of STAT3 had opposing effects on LKB1/AMPK/mTORC1- dependent tumorigenesis. Using genetic and pharmacological approaches, we identified LKB1 as a direct STAT3 target while repressing CREB. Furthermore, PCa patients with high CREB expression had inferior clinical outcome with significantly increased risk of disease and metastatic recurrence. We observe that castration state lowers STAT3 abundance and increases AR and CREB levels, leading to castration-resistant PCa (CRPC). Our findings revealed that STAT3 controls mTORC1 and CREB in metastatic disease, suggesting CREB as a promising target for lethal CRPC.
RNA origami scaffolds as a cryo-EM tool for investigating aptamer-ligand binding of a Broccoli-Pepper FRET pair
Authors: Vallina Néstor Sampedro , McRae Ewan K.S. , Hansen Bente Kring , Boussebayle Adrien , Andersen Ebbe Sloth 
Published: August 2022

ABSTRACTRNA nanotechnology uses motifs from nature as well as aptamers from in vitro selection to construct nanostructures and devices for applications in RNA medicine and synthetic biology. The RNA origami method allows cotranscriptional folding of large RNA scaffolds that can position functional motifs in a precise manner, which has been verified by Förster Resonance Energy Transfer (FRET) between fluorescent aptamers. Cryogenic electron microscopy (cryo-EM) is a promising method for characterizing the structure of larger RNA nanostructures. However, the structure of individual aptamers is difficult to solve by cryo-EM due to their low molecular weight. Here, we place aptamers on the RNA origami scaffolds to increase the contrast for cryo-EM and solve the structure of a new Broccoli-Pepper FRET pair. We identify different modes of ligand binding of the two aptamers and verify by selective probing. 3D variability analysis of the cryo-EM data show that the relative position between the two bound fluorophores on the origami fluctuate by only 3.5 Angstrom. Our results demonstrate the use of RNA origami scaffolds for characterizing small RNA motifs by cryo-EM and for positioning functional RNA motifs with high spatial precision. The Broccoli-Pepper apta-FRET pair has potential use for developing advanced sensors that are sensitive to small conformational changes.