bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carbon ion irradiation plus CTLA4 blockade elicits therapeutic immune responses in a murine tumor model
Authors: Hartmann Laura , Osen Wolfram , Eichmüller Oliver L. , Kordaß Theresa , Furkel Jennifer , Dickes Elke , Reid Carissa , Debus Jürgen , Brons Stephan , Abdollahi Amir , Moustafa Mahmoud , Rieken Stefan , Eichmüller Stefan B. 
Published: July 2022

AbstractRadiotherapy can act as an in situ vaccine thereby activating tumor-specific immune responses that prevent tumor outgrowth in treated patients. While carbon ion radiotherapy has shown superior biophysical properties over conventional photon irradiation, the immunological effects induced have remained largely uncovered. The combination of radiotherapy with immune checkpoint inhibition (radioimmunotherapy) aims at further enhancement of anti-tumor immunity; however, studies on the immune cell composition in irradiated and distant tumors following radioimmunotherapy with carbon ions are scarce. We have established a bilateral tumor model by time shifted transplantation of murine, Her2+ EO771 tumor cells onto the flanks of immune competent mice followed by selective irradiation of the primal tumor, while sparing the consecutive tumor. We demonstrate that αCTLA4-but not αPD-L1-based radioimmunotherapy induces complete tumor rejection in our model. Intriguingly, local tumor control caused in situ immunization resulting even in eradication of non-irradiated, distant tumors. Moreover, cured mice were protected against EO771 rechallenge indicative of long lasting, tumor-protective immunological memory. Deconvolution of the treatment induced immunological effects by single cell RNA-sequencing (scRNA-seq) and concomitant flow cytometric analyses revealed in irradiated tumors predominating myeloid cells that developed into distinct tumor-associated macrophage clusters with upregulated expression of TNF and IL1 responsive genes, as well as activation of NK cells. Non-irradiated tumors showed higher frequencies of naïve T cells in irradiated mice, which were activated when combined with CTLA4 blockade. In conclusion, radioimmunotherapy with carbon ions plus CTLA4 inhibition reshapes the tumor-infiltrating immune cell composition and can induce complete rejection even of non-irradiated tumors. Our data present a rationale to combine radiotherapy approach with CTLA4 blockade to achieve durable anti-tumor immunity. Evaluation of future radioimmunotherapy approaches should thus not only focus on the immunological impacts at the site of irradiation but should also consider systemic immunological effects that might affect outgrowth of non-irradiated tumors.
PDB ProtVista: A reusable and open-source sequence feature viewer
Authors: Deshpande Mandar , Varadi Mihaly , Paysan-Lafosse Typhaine , Nair Sreenath , Piovesan Damiano , Mir Saqib , Gutmanas Aleksandras , Tosatto Silvio C. E. , Velankar Sameer 
Published: July 2022

AbstractThe PDB ProtVista is a reusable and customisable sequence feature viewer that provides intuitive and detailed 2D visualisation of residue-level annotations while supporting interactive communication with 3D viewers. The Protein Data Bank in Europe (PDBe) team develops and maintains PDB ProtVista. Several public web services use it to display structural and functional annotations such as macromolecular interaction interfaces, intrinsic disorder predictions, sequence variants, and sequence conservation. The PDB ProtVista is freely available fromhttps://github.com/PDBeurope/protvista-pdb. We provide extensive documentation and step-by-step user guides on integrating PDB ProtVista with existing web applications and 3D molecular viewers. We also offer examples of displaying the user’s custom data and functional annotations for PDB and UniProt entries powered by a rich set of PDBe API endpoints.
Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 receptors in the head twitch response induced by 5-hydroxytryptophan and psilocybin: Translational implications
Authors: Shahar Orr , Botvinnik Alexander , Esh-Zuntz Noam , Brownstien Michal , Wolf Rachel , Wolf Gilly , Lerer Bernard , Lifschytz Tzuri 
Published: July 2022

AbstractThere is increasing interest in the therapeutic potential of psilocybin in psychiatric disorders. In common with other serotonergic psychedelics, psilocybin is thought to act via the 5-HT2A receptor (5-HT2AR). Serotonin is the endogenous ligand of 5-HTR. In rodents, the serotonin precursor, 5-hydroxytryptophan (5-HTP), and psilocybin, induce a characteristic head twitch response (HTR), which is correlated with the human psychedelic trip in intensity and duration. We examined the role of other serotonergic receptors and the trace amine associated receptor 1 (TAAR1) in modulating HTR induced by 5-HTP and psilocybin. Male C57BL/6J mice (11 weeks old, ~30g) were administered 5-HTP, 50-250 mg/kg intraperitoneally (i.p.) or 200 mg/kg i.p. after pretreatment with 5-HT/TAAR1 receptor modulators. Psilocybin was administered at 0.1-51.2 mg/kg i.p. or at 4.4 mg/kg i.p. preceded by 5-HT/TAAR1 receptor modulators. HTR was assessed in a custom-built magnetometer. 5-HTP and psilocybin induced a dose dependent increase in the frequency of HTR over 20 minutes with attenuation by the 5-HT2AR antagonist, M100907 (volanserin), and the 5-HT1AR agonist, 8-OH-DPAT. The 5-HT2CR antagonist, RS102221, enhanced HTR at lower doses but reduced it at higher doses for 5-HTP and psilocybin. The TAAR1 antagonist, EPPTB, reduced 5-HTP-but not psilocybin-induced HTR. We have confirmed the key role of 5-HT2AR in HTR and have demonstrated an effect of 5-HT1AR and a bimodal contribution of 5-HT2CR as well as a role of TAAR1 in modulating HTR induced by 5-HTP. Compounds that modulate HTR induced by psychedelics have a potentially important role in the emerging therapeutic use of these compounds.Significance StatementWe have confirmed the key role of 5-HT2AR in in the induction of HTR by 5-HTP and psilocybin, have demonstrated the effect of a 5-HT1AR agonist to attenuate HTR and a bimodal contribution of 5-HT2CR as well as a role of TAAR1 in modulating HTR induced by 5-HTP. Compounds that modulate HTR induced by psychedelics have a potentially important role in the emerging therapeutic use of these compounds.Visual Abstract
Harnessing machine translation methods for sequence alignment
Authors: Dotan Edo , Belinkov Yonatan , Avram Oren , Wygoda Elya , Ecker Noa , Alburquerque Michael , Keren Omri , Loewenthal Gil , Pupko Tal 
Published: July 2022

AbstractThe sequence alignment problem is one of the most fundamental problems in bioinformatics and a plethora of methods were devised to tackle it. Here we introduce BetaAlign, a novel methodology for aligning sequences using a natural language processing (NLP) approach. BetaAlign accounts for the possible variability of the evolutionary process among different datasets by using an ensemble of transformers, each trained on millions of samples generated from a different evolutionary model. Our approach leads to outstanding alignment accuracy, often outperforming commonly used methods, such as MAFFT, DIALIGN, ClustalW, T-Coffee, and MUSCLE. Notably, the utilization of deep-learning techniques for the sequence alignment problem brings additional advantages, such as automatic feature extraction that can be leveraged for a variety of downstream analysis tasks.
Model-Based Estimates for Operant Selection
Authors: Borgstede Matthias , Anselme Patrick 
Published: July 2022

AbstractWe present a new methodology to partition different sources of behavior change within a selectionist framework based on the Price equation – the Multilevel Model of Behavioral Selection (MLBS). The MLBS provides a theoretical background to describe behavior change in terms of operant selection. Operant selection is formally captured by the covariance based law of effect (CLOE) and accounts for all changes in individual behavior that involve a covariance between behavior and predictors of evolutionary fitness (e.g., food). In this article we show how the CLOE may be applied to different components of operant behavior (e.g., allocation, speed, and accuracy of responding), thereby providing quantitative estimates for various selection effects affecting behavior change using data from a published learning experiment in pigeons.
Analysis of the mechanism of castor tolerance to Cd metal based on proteomics and metabolomics
Authors: Huibo Zhao , Yong Zhao , Rui Luo , Guorui Li , Jianjun Di , Qi Wen , Xiaotian Liang , Mingda Yin , Yanpeng Wen , Zhiyan Wang , Fenglan Huang 
Published: July 2022

AbstractThe pollution of soil with heavy metals is an increasingly serious worldwide problem, and cadmium (Cd) has attracted attention because of its high toxicity to almost all plants. Since castor tolerates the accumulation of heavy metals, it has the potential for heavy metal soil remediation. We studied the mechanism of the tolerance of castor to Cd stress treatments at three doses: 300 mg/L, 700 mg/L, and 1,000 mg/L. Our research provides new ideas for revealing the defense and detoxification mechanisms of Cd-stressed castor. By combining the results of physiology, differential proteomics and comparative metabolomics, we conducted a comprehensive analysis of the networks that regulate the response of castor to Cd stress. The physiological results mainly emphasize the super-sensitive responses of castor plant roots to Cd stress and the effects of Cd stress on plants’ antioxidant system, ATP synthesis and ion homeostasis. We confirmed these results at the protein and metabolite levels. At the same time, proteomics and metabolomics show that castor plants mainly block the root system’s absorption of Cd2+ by enhancing the strength of the cell wall, and inducing programmed cell death in response to the three different doses of Cd stress. In addition, the plasma membrane ATPase encoding gene (RcHA4), which was significantly upregulated in our differential proteomics and RT-qPCR studies, was transgenically overexpressed in wild type Arabidopsis thaliana for functional verification. The results indicated that this gene plays an important role in improving plant Cd tolerance.
Asteroid: a new minimum balanced evolution supertree algorithm robust to missing data
Authors: Morel Benoit , Williams Tom A. , Stamatakis Alexandros 
Published: July 2022

AbstractMotivationMissing data and incomplete lineage sorting are two major obstacles to accurate species tree inference. Gene tree methods such as ASTRAL and ASTRID have been developed to account for incomplete lineage sorting. However, they can be severely affected by high levels of missing data.ResultsWe present Asteroid, a novel supertree method that infers an unrooted species tree from a set of unrooted gene trees. We show on both empirical and simulated datasets that Asteroid is more robust to missing data than ASTRAL and ASTRID, while being several orders of magnitude faster than ASTRAL for datasets that contain thousands of genes. Asteroid offers advanced features such as parallelization, support value computation, and support for multi-copy and multifurcating gene trees.AvailabilityAsteroid is freely available at https://github.com/BenoitMorel/AsteroidContactbenoit.morel@h-its.org online.
Comparing retinotopic maps of children and adults reveals a late-stage change in how V1 samples the visual field
Authors: Himmelberg Marc M. , Tünçok Ekin , Gomez Jesse , Grill-Spector Kalanit , Carrasco Marisa , Winawer Jonathan 
Published: July 2022

ABSTRACTAdult visual performance differs with angular location –it is better for stimuli along the horizontal than vertical, and lower than upper vertical meridian of the visual field. These perceptual asymmetries are paralleled by asymmetries in cortical surface area in primary visual cortex (V1). Children, unlike adults, have similar visual performance at the lower and upper vertical meridian. Do children have similar V1 surface area representing the upper and lower vertical meridian? Using MRI, we measure the surface area of retinotopic maps (V1-V3) in children and adults. Many features of the maps are similar between groups, including greater V1 surface area for the horizontal than vertical meridian. However, unlike adults, children have a similar amount of V1 surface area representing the lower and upper vertical meridian. These data reveal a late-stage change in V1 organization that may relate to the emergence of the visual performance asymmetry along the vertical meridian by adulthood.
An assessment of Nano-RECall: Interpretation of Oxford Nanopore sequence data for HIV-1 drug resistance testing
Authors: Delaney Kayla Eileen , Ngobeni Trevor , Woods Conan K. , Gordijn Carli , Claassen Mathilda , Parikh Urvi , Harrigan P. Richard , van Zyl Gert Uves 
Published: July 2022

AbstractIntroductionOxford Nanopore Technologies (ONT) offer sequencing with low-capital-layout sequencing options, which could assist in expanding HIV drug resistance testing to resource limited settings. However, sequence analysis remains time time-consuming and reliant on skilled personnel. Moreover, current ONT bioinformatic pipelines provide a single consensus sequence that is not equivalent to Sanger sequencing, as drug resistance is often detected in mixed populations. We have therefore investigated an integrated bioinformatic pipeline, Nano-RECall, for seamless drug resistance of low read coverage ONT sequence data from affordable Flongle or MinION flow cells.MethodsWe compared Sanger sequencing to ONT sequencing of the same HIV-1 subtype C polymerase chain reaction (PCR) amplicons, respectively using RECall and the novel Nano-RECall bioinformatics pipelines. Amplicons were from separate assays a) Applied Biosystems HIV-1 Genotyping Kit (ThermoFisher) spanning protease (PR) to reverse transcriptase (RT) (PR-RT) (n=46) and b) homebrew integrase (IN) (n=21). We investigated optimal read-depth by assessing the coefficient of variation (CV) of nucleotide proportions for various read-depths; and between replicates of 400 reads. The agreement between Sanger sequences and ONT sequences were assessed at nucleotide level, and at codon level for Stanford HIV drug resistance database mutations.ResultsThe coefficient of variation of ONT minority variants plateaued after a read depth of 400-fold implying limited benefit of additional depth and replicates of 400 reads showed a CV of ∼6 % for a representative position. The average sequence similarity between ONT and Sanger sequences was 99.3% (95% CI: 99.1-99.4%) for PR-RT and 99.6% (95% CI: 99.4-99.7%) for INT. Drug resistance mutations did not differ for 21 IN sequences; 16 mutations were detected by both ONT- and Sanger sequencing. For the 46 PR and RT sequences, 245 mutations were detected by either ONT or Sanger, of these 238 (97.1%) were detected by both.ConclusionsThe Nano-RECall pipeline, freely available as a downloadable application on a Windows computer, provides Sanger-equivalent HIV drug resistance interpretation. This novel pipeline combined with a simple workflow and multiplexing samples on ONT flow-cells would contribute to making HIV drug resistance sequencing feasible for resource limited settings.
Multispecies biofilm architecture determines bacterial exposure to phages
Authors: Winans James B. , Wucher Benjamin R. , Nadell Carey D. 
Published: July 2022

AbstractNumerous ecological interactions among microbes – for example, competition for space and resources, or interaction among phages and their bacterial hosts – are likely to occur simultaneously in multispecies biofilm communities. While biofilms formed by just a single species occur, multispecies biofilms are thought to be more typical of microbial communities in the natural environment. Previous work has shown that multispecies biofilms can increase, decrease, or have no measurable impact on phage exposure of a host bacterium living alongside another species that the phages cannot target. The reasons underlying this variability are not well understood, and how phage-host encounters change within multispecies biofilms remains mostly unexplored at the cellular spatial scale. Here, we study how the cellular scale architecture of model 2-species biofilms impacts cell-cell and cell-phage interactions controlling larger scale population and community dynamics. Our system consists of dual-culture biofilms ofEscherichia coliandVibrio choleraeunder exposure to T7 phages, which we study using microfluidic culture, high resolution confocal microscopy imaging, and detailed image analysis. As shown previously, sufficiently mature biofilms ofE. colican protect themselves from phage exposure via their curli matrix. Before this stage of biofilm structural maturity,E. coliis highly susceptible to phages, however we show that these bacteria can gain lasting protection against phage exposure if they have become embedded in the bottom layers of highly packed groups ofV. choleraein co-culture. This protection, in turn, is dependent on the cell packing architecture controlled byV. choleraebiofilm matrix secretion. In this manner,E. colicells that are otherwise susceptible to phage mediated killing can survive phage exposure in the absence ofde novoresistance evolution. While co-culture biofilm formation withV. choleraecan confer phage protection toE. coli, it comes at the cost of competing withV. choleraeand a disruption of normal curli-mediated protection forE. colieven in dual species biofilms grown over long time scales. This work highlights the critical importance of studying multispecies biofilm architecture and its influence on the community dynamics of bacteria and phages.Short blurbMultispecies bacterial biofilm architecture qualitatively alters the spatial patterns of phage exposure and the community dynamics of matrix production, interspecific competition, and phage propagation.
Conserved and diverged mechanisms for RNA target-site recognition by the multi KH-domain Bicaudal C protein
Authors: Dowdle Megan E. , Tonelli Tommaso Pietro , Fox Catherine A. , Sheets Michael D. 
Published: July 2022

ABSTRACTThe Bicaudal-C (Bicc1) multi-KH domain RNA binding protein controls cell fates by binding and repressing the translation of specific target mRNAs. To provide new insights into Bicc1-RNA binding we used quantitative assays to analyze interactions between Xenopus Bicc1 protein and the 32-nt Bicc1 RNA target site from XlCripto-1 mRNA. High-affinity binding by XlBicc1(Kd=34nM) required both a 5’ leader sequence and a 3’loop sequence. Bicc1 proteins from humans (HsBicc1), zebrafish (DrBicc1) and fruit flies (DmBicc1) also bound the XlCripto-1 RNA with high-affinity via an interaction requiring the 5’ leader sequence, providing evidence for a conserved mechanism of RNA recognition by Bicc1. However, in contrast to XlBicc1, each of the other species’ Bicc1s showed a significantly relaxed requirement for the 3’ loop sequence. Analyses of mutant forms of XlBicc1, revealed that the KH1 domain promoted Bicc1’s requirement for the loop sequence via a GXXG-independent mechanism. In addition, a fusion protein comprised of the XlKH1 and the DmBicc1-KH2-KH3 subdomains was sufficient to establish high-affinity, loop-sensitive Bicc1-binding to XlCripto-1 RNA. These data support a model wherein the KH2 domain interacts with the leader sequence via a GXXG-mediated KH-RNA interface, defining the conserved core of the metazoan Bicc1-RNA interaction, while the KH1 domain is required for the formation of a more flexible, secondary protein-RNA interface that allows recognition of the 3’ loop sequence. This secondary interface differs between species and possibly between target mRNAs, establishing the potential for a range of translational repression activities for Bicc1 target mRNAs.
Cortical surface electrical potentials are composed of multiple bandlimited frequency components, including high-gamma
Authors: Livezey Jesse A. , Hwang Ahyeon , Usovich Kseniya , Dougherty Maximilian E. , Chang Edward F. , Bouchard Kristofer E. 
Published: July 2022

AbstractA common challenge in neuroscience is how to decompose noisy, multi-source signals measured in experiments into biophysically interpretable components. Analysis of cortical surface electrical potentials (CSEPs) measured using electrocorticography arrays (ECoG) typifies this problem. We hypothesized that high frequency (70-1,000 Hz) CSEPs are composed of broadband (i.e., power-law) and bandlimited components with potentially differing biophysical origins. In particular, the high-gamma band (70-150 Hz) has been shown to be highly predictive for encoding and decoding behaviors and stimuli. Despite its demonstrated importance, whether high-gamma is composed of a bandlimited signal is poorly understood. To address this gap, we recorded CSEPs from rat auditory cortex and demonstrate that the evoked CSEPs are composed of multiple distinct frequency components, including high-gamma. We then show, using a novel robust regression method, that at fast timescales and on single trials during speech production, human high-gamma amplitude cannot be explained by a modulating power-law component; thus, high-gamma is band-limited. Furthermore, we show that the power-law component is less predictive of produced speech compared to the raw high-gamma amplitude. Finally, we show that the largest variance component of human ECoG signals is low-frequency and band-limited, not broadband. Together these results demonstrate that there are multiple, band-limited components of high frequency power in cortical surface electrical potentials, including the high-gamma band, which may have different biophysical origins.Significance StatementElectrocortigraphy (ECoG) records cortical surface electrical potentials (CSEPs). ECoG is utilized in both humans and animal models to understand distributed cortical processing and for brain machine interfaces. The spectral structure of evoked CSEPs is greatly debated. To address this issue, we recorded from rat auditory cortex using µECoG and human ventral sensory-motor cortex during speech production with high-density ECoG. Using novel analytic approaches, we found that evoked CSEPs are composed of multiple band-limited components, including high-gamma. These results contrast with the dominant thinking in the field that the high-frequency power in ECoG is broadband. Our results raise the possibility that distinct frequency components of ECoG are biomarkers of processing in different cortical layers.