bluuebunny/crossref_metadata_2025_split huggingface dataset:
Death of tonsillar B cells by NETosis
Authors: Bukhari Ameera , Kalinina Olga , Knight Katherine L. 
Published: March 2023

AbstractRegulating B cell death is essential for generating antibodies and maintaining immune tolerance. B cells can die by apoptosis, and we report that human tonsil B cells, but not peripheral blood B cells also die by NETosis. This cell death is density-dependent, characterized by the loss of cell and nuclear membrane integrity, release of reactive oxygen species, and chromatin decondensation. Tonsil B cells secrete high levels of TNF, and inhibiting TNF prevented chromatin decondensation. By in situ fluorescence microscopy, B cell NETosis, as identified by the hyper citrullination of Histone-3, was localized to the light zone (LZ) of germinal centers in normal tonsil and overlapped with the B cell marker CD19/IgM. We propose a model in which stimulation of B cells in the LZ induces NETosis, driven in part by TNF. We also provide evidence that NETosis of tonsil B cells may be inhibited by an unidentified factor in tonsil. The results describe a previously unidentified form of B cell death and suggest a new mechanism to maintain B cell homeostasis during immune responses.
The plant unique ESCRT component FREE1 regulates autophagosome closure
Authors: Zeng Yonglun , Li Baiying , Huang Shuxian , Li Hongbo , Cao Wenhan , Chen Yixuan , Liu Guoyong , Li Zhenping , Yang Chao , Feng Lei , Gao Jiayang , Lo Sze Wan , Zhao Jierui , Shen Jinbo , Guo Yan , Gao Caiji , Dagdas Yasin , Jiang Liwen 
Published: March 2023

AbstractThe energy sensor AMP-activated protein kinase (AMPK) can activate autophagy when cellular energy production becomes compromised. However, the degree to which nutrient sensing impinges on the autophagosome closure remains unknown. Here, we provide the mechanism underlying a plant unique protein FREE1, upon autophagy-induced SnRK1α1-mediated phosphorylation, functions as a linkage between ATG conjugation system and ESCRT machinery to regulate the autophagosome closure upon nutrient deprivation. Using high-resolution microscopy, 3D-electron tomography, and protease protection assay, we showed that unclosed autophagosomes accumulated in free1 mutants. Proteomic, cellular and biochemical analysis revealed the mechanistic connection between FREE1 and the ATG conjugation system/ESCRT-III complex in regulating autophagosome closure. Mass spectrometry analysis showed that the evolutionary conserved plant energy sensor SnRK1α1 phosphorylates FREE1 and recruits it to the autophagosomes to promote closure. Mutagenesis of the phosphorylation site on FREE1 caused the autophagosome closure failure. Our findings unveil how cellular energy sensing pathways regulate autophagosome closure to maintain cellular homeostasis.
A Vaccinia-based system for directed evolution of GPCRs in mammalian cells
Authors: Klenk Christoph , Scrivens Maria , Niederer Anina , Shi Shuying , Mueller Loretta , Gersz Elaine , Zauderer Maurice , Smith Ernest S. , Strohner Ralf , Plückthun Andreas 
Published: March 2023

AbstractDirected evolution in bacterial or yeast display systems has been successfully used to improve stability and expression of G protein-coupled receptors for structural and biophysical studies. Yet, several receptors cannot be tackled in microbial systems due to their complex molecular composition or unfavorable ligand properties. Here, we report an approach to evolve G protein-coupled receptors in mammalian cells. To achieve clonality and uniform expression, we develop a viral transduction system based on Vaccinia virus. By rational design of synthetic DNA libraries, we first evolve neurotensin receptor 1 for high stability and expression. Second, we demonstrate that receptors with complex molecular architectures and large ligands, such as the parathyroid hormone 1 receptor, can be readily evolved. Importantly, functional receptor properties can now be evolved in the presence of the mammalian signaling environment, resulting in receptor variants exhibiting increased allosteric coupling between the ligand binding site and the G protein interface. Our approach thus provides insights into the intricate molecular interplay required for GPCR activation.
Comprehensive proteogenomic characterization of early duodenal cancer reveals the carcinogenesis tracks of different subtypes
Authors: Li Lingling , Jiang Dongxian , Liu Hui , Guo Chunmei , Zhao Rui , Zhang Qiao , Xu Chen , Qin Zhaoyu , Feng Jinwen , Liu Yang , Wang Haixing , Chen Weijie , Zhang Xue , Li Bin , Bai Lin , Tian Sha , Tan Subei , Yu Zixiang , Chen Lingli , Huang Jie , Zhao Jian-Yuan , Hou Yingyong , Ding Chen 
Published: March 2023

AbstractThe subtypes of duodenal cancer (DC) are complicated and the carcinogenesis process is not well characterized. We present comprehensive characterization of 438 samples from 156 DC patients, covering 2 major and 5 rare subtypes. Proteogenomics reveals LYN amplification at the chromosome 8q gain functioned in the transmit from intraepithelial neoplasia phase to infiltration tumor phase via MAPK signaling, and illustrates the DST mutation improves mTOR signaling in the duodenal adenocarcinoma stage. Proteome-based analysis elucidates stage-specific molecular characterizations and carcinogenesis tracks, and defines the cancer-driving waves of the adenocarcinoma and Brunner’s gland subtypes. The drug-targetable alanyl-tRNA synthetase (AARS1) in the high tumor mutation burden/immune infiltration is significantly enhanced in DC progression, and catalyzes the lysine-alanylation of poly-ADP-ribose polymerases (PARP1), which decreases the apoptosis of cancer cells, eventually promoting cell proliferation and tumorigenesis. We assess the proteogenomic landscape of early DC, and provide insights into the molecular features corresponding therapeutic targets.
Activation of the CA2-ventral CA1 pathway reverses social discrimination dysfunction in Shank3B knockout mice
Authors: Cope Elise C. , Wang Samantha H. , Waters Renée C. , Gore Isha R. , Vasquez Betsy , Laham Blake J. , Gould Elizabeth 
Published: March 2023

AbstractMutation or deletion of theSHANK3gene, which encodes a synaptic scaffolding protein, is linked to autism spectrum disorder and Phelan-McDermid syndrome, conditions associated with social memory impairments.Shank3Bknockout mice also exhibit social memory deficits. The CA2 region of the hippocampus integrates numerous inputs and sends a major output to the ventral CA1 (vCA1). Despite finding few differences in excitatory afferents to the CA2 inShank3Bknockout mice, we found that activation of CA2 neurons as well as the CA2-vCA1 pathway restored social recognition function to wildtype levels. vCA1 neuronal oscillations have been linked to social memory, but we observed no differences in these measures between wildtype andShank3Bknockout mice. However, activation of the CA2 enhanced vCA1 theta power inShank3Bknockout mice, concurrent with behavioral improvements. These findings suggest that stimulating adult circuitry in a mouse model with neurodevelopmental impairments can invoke latent social memory function.
The RNA-binding protein hnRNP F is required for the germinal center B cell response
Authors: Huang Hengjun , Li Yuxing , Zhang Gaopu , Ruan Gui-Xin , Zhu Zhijian , Chen Wenjing , Zou Jia , Zhang Rui , Wang Jing , Ouyang Yu , Xu Shengli , Ou Xijun 
Published: March 2023

AbstractThe T cell-dependent (TD) antibody response involves the generation of high affinity, immunoglobulin heavy chain class-switched antibodies that are generated through germinal center (GC) response. This process is controlled by coordinated transcriptional and post-transcriptional gene regulatory mechanisms. RNA-binding proteins (RBPs) have emerged as critical players in post-transcriptional gene regulation. Here we demonstrate that B cell-specific deletion of RBP hnRNP F leads to diminished production of class-switched antibodies with high affinities in response to a TD antigen challenge. B cells deficient in hnRNP F are characterized by defective proliferation and c-Myc upregulation upon antigenic stimulation. Mechanistically, hnRNP F directly binds to the G-tracts of Cd40 pre-mRNA to promote the inclusion of Cd40 exon 6 that encodes its transmembrane domain, thus enabling appropriate CD40 cell surface expression. Furthermore, we find that hnRNP A1 and A2B1 can bind to the same region of Cd40 pre-mRNA but suppress exon 6 inclusion, suggesting that these hnRNPs and hnRNP F might antagonize each-other’s effects on Cd40 splicing. In summary, our study uncovers an important posttranscriptional mechanism regulating the GC response.
White matter disconnection of left multiple demand network is associated with post-lesion deficits in cognitive control
Authors: Jiang Jiefeng , Bruss Joel , Lee Woo-Tek , Tranel Daniel , Boes Aaron D. 
Published: March 2023

AbstractCognitive control modulates other cognitive functions to achieve internal goals and is important for adaptive behavior. Cognitive control is enabled by the neural computations distributed over cortical and subcortical areas. However, due to technical challenges in recording neural activity from the white matter, little is known about the anatomy of white matter tracts that coordinate the distributed neural computations that support cognitive control. Here, we leverage a large sample of human patients with focal brain lesions (n = 643) and investigate how lesion location and connectivity profiles account for variance in cognitive control performance. We find that lesions in white matter connecting left frontoparietal regions of the multiple demand network reliably predict deficits in cognitive control performance. These findings advance our understanding of the white matter correlates of cognitive control and provide an approach for incorporating network disconnection to predict deficits following lesions.
Hypothalamic melanin-concentrating hormone neurons integrate food-motivated appetitive and consummatory processes in rats
Authors: Subramanian Keshav S. , Lauer Logan Tierno , Hayes Anna M. R. , Décarie-Spain Léa , McBurnett Kara , Nourbash Anna C. , Donohue Kristen N. , Kao Alicia E. , Bashaw Alexander G. , Burdakov Denis , Noble Emily E. , Schier Lindsey A. , Kanoski Scott E. 
Published: March 2023

AbstractThe lateral hypothalamic area (LHA) integrates homeostatic processes and reward-motivated behaviors. Here we show that LHA neurons that produce melanin-concentrating hormone (MCH) are dynamically responsive to both food-directed appetitive and consummatory processes in male rats. Specifically, results reveal that MCH neuron Ca2+ activity increases in response to both discrete and contextual food-predictive cues and is correlated with food-motivated responses. MCH neuron activity also increases during eating, and this response is highly predictive of caloric consumption and declines throughout a meal, thus supporting a role for MCH neurons in the positive feedback consummatory process known as appetition. These physiological MCH neural responses are functionally relevant as chemogenetic MCH neuron activation promotes appetitive behavioral responses to food-predictive cues and increases meal size. Finally, MCH neuron activation enhances preference for a noncaloric flavor paired with intragastric glucose. Collectively, these data identify a hypothalamic neural population that orchestrates both food-motivated appetitive and intake-promoting consummatory processes.
Post-acute sequelae of COVID-19 is characterized by diminished peripheral CD8+β7 integrin+ T cells and anti-SARS-CoV-2 IgA response
Authors: Santa Cruz André , Mendes-Frias Ana , Azarias-da-Silva Marne , André Sónia , Oliveira Ana Isabel , Pires Olga , Mendes Marta , Oliveira Bárbara , Braga Marta , Lopes Joana Rita , Domingues Rui , Costa Ricardo , Silva Luís Neves , Matos Ana Rita , Ângela Cristina , Costa Patrício , Carvalho Alexandre , Capela Carlos , Pedrosa Jorge , Castro António Gil , Estaquier Jérôme , Silvestre Ricardo 
Published: March 2023

AbstractSeveral millions of individuals are estimated to develop post-acute sequelae SARS-CoV-2 condition (PASC) that persists for months after infection. Here we evaluate the immune response in convalescent individuals with PASC compared to convalescent asymptomatic and uninfected participants, six months following their COVID-19 diagnosis. Both convalescent asymptomatic and PASC cases are characterised by higher CD8+ T cell percentages, however, the proportion of blood CD8+ T cells expressing the mucosal homing receptor β7 is low in PASC patients. CD8 T cells show increased expression of PD-1, perforin and granzyme B in PASC, and the plasma levels of type I and type III (mucosal) interferons are elevated. The humoral response is characterized by higher levels of IgA against the N and S viral proteins, particularly in those individuals who had severe acute disease. Our results also show that consistently elevated levels of IL-6, IL-8/CXCL8 and IP-10/CXCL10 during acute disease increase the risk to develop PASC. In summary, our study indicates that PASC is defined by persisting immunological dysfunction as late as six months following SARS-CoV-2 infection, including alterations in mucosal immune parameters, redistribution of mucosal CD8+β7Integrin+ T cells and IgA, indicative of potential viral persistence and mucosal involvement in the etiopathology of PASC.
Screw sense excess and reversals of helical polymers in solution
Authors: Rey-Tarrío Francisco , Rodríguez Rafael , Quiñoá Emilio , Freire Félix 
Published: March 2023

AbstractThe helix reversal is a structural motif found in helical polymers in the solid state, but whose existence is elusive in solution. Herein, we have shown how the photochemical electrocyclization (PEC) of poly(phenylacetylene)s (PPAs) can be used to determine not only the presence of helix reversals in polymer solution, but also to estimate the screw sense excess. To perform these studies, we used a library of well folded PPAs and different copolymers series made by enantiomeric comonomers that show chiral conflict effect. The results obtained indicate that the PEC of a PPA will depend on the helical scaffold adopted by the PPA backbone and on its folding degree. Then, from these studies it is possible to determine the screw sense excess of a PPA, highly important in applications such as chiral stationary phases in HPLC or asymmetric synthesis.
A-MYB and BRDT-dependent RNA Polymerase II pause release orchestrates transcriptional regulation in mammalian meiosis
Authors: Alexander Adriana K. , Rice Edward J. , Lujic Jelena , Simon Leah E. , Tanis Stephanie , Barshad Gilad , Zhu Lina , Lama Jyoti , Cohen Paula E. , Danko Charles G. 
Published: March 2023

AbstractDuring meiotic prophase I, spermatocytes must balance transcriptional activation with homologous recombination and chromosome synapsis, biological processes requiring extensive changes to chromatin state. We explored the interplay between chromatin accessibility and transcription through prophase I of mammalian meiosis by measuring genome-wide patterns of chromatin accessibility, nascent transcription, and processed mRNA. We find that Pol II is loaded on chromatin and maintained in a paused state early during prophase I. In later stages, paused Pol II is released in a coordinated transcriptional burst mediated by the transcription factors A-MYB and BRDT, resulting in ~3-fold increase in transcription. Transcriptional activity is temporally and spatially segregated from key steps of meiotic recombination: double strand breaks show evidence of chromatin accessibility earlier during prophase I and at distinct loci from those undergoing transcriptional activation, despite shared chromatin marks. Our findings reveal mechanisms underlying chromatin specialization in either transcription or recombination in meiotic cells.
MS2Query: reliable and scalable MS2 mass spectra-based analogue search
Authors: de Jonge Niek F. , Louwen Joris J. R. , Chekmeneva Elena , Camuzeaux Stephane , Vermeir Femke J. , Jansen Robert S. , Huber Florian , van der Hooft Justin J. J. 
Published: March 2023

AbstractMetabolomics-driven discoveries of biological samples remain hampered by the grand challenge of metabolite annotation and identification. Only few metabolites have an annotated spectrum in spectral libraries; hence, searching only for exact library matches generally returns a few hits. An attractive alternative is searching for so-called analogues as a starting point for structural annotations; analogues are library molecules which are not exact matches but display a high chemical similarity. However, current analogue search implementations are not yet very reliable and relatively slow. Here, we present MS2Query, a machine learning-based tool that integrates mass spectral embedding-based chemical similarity predictors (Spec2Vec and MS2Deepscore) as well as detected precursor masses to rank potential analogues and exact matches. Benchmarking MS2Query on reference mass spectra and experimental case studies demonstrate improved reliability and scalability. Thereby, MS2Query offers exciting opportunities to further increase the annotation rate of metabolomics profiles of complex metabolite mixtures and to discover new biology.
The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion
Authors: Onuchic Laura , Padovano Valeria , Schena Giorgia , Rajendran Vanathy , Dong Ke , Shi Xiaojian , Pandya Raj , Rai Victoria , Gresko Nikolay P. , Ahmed Omair , Lam TuKiet T. , Wang Weiwei , Shen Hongying , Somlo Stefan , Caplan Michael J. 
Published: March 2023

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is the most prevalent potentially lethal monogenic disorder. Mutations in the PKD1 gene, which encodes polycystin-1 (PC1), account for approximately 78% of cases. PC1 is a large 462-kDa protein that undergoes cleavage in its N and C-terminal domains. C-terminal cleavage produces fragments that translocate to mitochondria. We show that transgenic expression of a protein corresponding to the final 200 amino acid (aa) residues of PC1 in two Pkd1-KO orthologous murine models of ADPKD suppresses cystic phenotype and preserves renal function. This suppression depends upon an interaction between the C-terminal tail of PC1 and the mitochondrial enzyme Nicotinamide Nucleotide Transhydrogenase (NNT). This interaction modulates tubular/cyst cell proliferation, the metabolic profile, mitochondrial function, and the redox state. Together, these results suggest that a short fragment of PC1 is sufficient to suppress cystic phenotype and open the door to the exploration of gene therapy strategies for ADPKD.
Durable responses in patients with HER2+ breast cancer and leptomeningeal metastases treated with trastuzumab deruxtecan
Authors: Alder Laura , Trapani Dario , Bradbury Claire , Van Swearingen Amanda E. D. , Tolaney Sara M. , Khasraw Mustafa , Anders Carey K. , Lascola Christopher D. , Hsu Liangge , Lin Nancy U. , Sammons Sarah 
Published: March 2023

AbstractLeptomeningeal metastases (LM) are a devastating complication of HER2 + metastatic breast cancer (MBC), with no effective treatments. In a case series of 8 patients with heavily pretreated HER2 + MBC and progressing LM, all 8 patients (100%) derived clinical benefit from Trastuzumab deruxtecan (TDXd), and 4 patients (50%) had an objective partial response based on formal neuroradiology MRI reads using the EORTC/RANO-LM Revised-Scorecard. T-DXd warrants further study in LM in HER2 + MBC and solid tumors where T-DXd may be active.
GazeBaseVR, a large-scale, longitudinal, binocular eye-tracking dataset collected in virtual reality
Authors: Lohr Dillon , Aziz Samantha , Friedman Lee , Komogortsev Oleg V. 
Published: March 2023

AbstractWe present GazeBaseVR, a large-scale, longitudinal, binocular eye-tracking (ET) dataset collected at 250 Hz with an ET-enabled virtual-reality (VR) headset. GazeBaseVR comprises 5,020 binocular recordings from a diverse population of 407 college-aged participants. Participants were recorded up to six times each over a 26-month period, each time performing a series of five different ET tasks: (1) a vergence task, (2) a horizontal smooth pursuit task, (3) a video-viewing task, (4) a self-paced reading task, and (5) a random oblique saccade task. Many of these participants have also been recorded for two previously published datasets with different ET devices, and 11 participants were recorded before and after COVID-19 infection and recovery. GazeBaseVR is suitable for a wide range of research on ET data in VR devices, especially eye movement biometrics due to its large population and longitudinal nature. In addition to ET data, additional participant details are provided to enable further research on topics such as fairness.
Alternative culture medium design for biomass production of autochthonous meat starter Latilactobacillus sakei sp. sakei ACU-2
Authors: Galante Nadia , Palavecino Prpich Noelia , Campos Carmen , Cayré María Elisa , Castro Marcela 
Published: March 2023

AbstractThe autochthonous strain Latilactobacillus sakei sp. sakei ACU-2 was selected as a meat starter culture for dry sausage production. Transferring this strain from laboratory scale to industry requires an increase in biomass production, while lowering process costs. In this study, a combination of techniques was applied in order to optimize the culture medium composition to enhance biomass production of L. sakei ACU-2. One variable at a time experiments, Plackett–Burman design, and mixture design were performed to fulfill the strain nutritional requirements. Eventually, the optimized formulation contained 19.46 g/L yeast extract; 8.28 g/L whey protein concentrate; 2.26 g/L soy peptone; 30 g/L cerelose; 1 g/L Tween 80; 5 g/L sodium acetate; 0.2 g/L magnesium sulfate and 0.05 g/L manganese sulfate. When L. sakei ACU-2 was cultivated in a bioreactor using the alternative medium, an enhancement of 75.5% of biomass production was achieved, in comparison to its growth in the commercial de Man, Rogosa, and Sharpe medium. Furthermore, a reduction of 62–86% of the cost was also attained. These results support a promising large-scale application of the designed medium for high biomass yields of the starter culture at minor costs.