bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma cells in human pancreatic ductal adenocarcinoma secrete antibodies to self-antigens
Authors: Yao Min , Preall Jonathan , Yeh Johannes , Pappin Darryl , Cifani Paolo , Zhao Yixin , Shen Sophia , Moresco Philip , He Brian , Patel Hardik , Habowski Amber , King Daniel A. , Raphael Kara , Rishi Arvind , Sejpal Divyesh , Weiss Matthew , Tuveson David , Fearon Douglas 
Published: March 2023

AbstractIntratumoral B cell responses are associated with more favorable clinical outcomes in human pancreatic ductal adenocarcinoma (PDAC). However, the antigens driving these B cell responses are largely unknown. We sought to discover these antigens by using single-cell RNA sequencing (scRNA-Seq) and immunoglobulin (Ig) sequencing of tumor-infiltrating immune cells from seven primary PDAC samples. We identified activated T and B cell responses and evidence of germinal center reactions. Ig sequencing identified plasma cell (PC) clones expressing isotype-switched and hyper-mutated Igs, suggesting the occurrence of T cell-dependent B cell responses. We assessed the reactivity of 41 recombinant antibodies that represented the products of 235 PCs and 12 B cells toward multiple cell lines and PDAC tissues, and observed frequent staining of intracellular self-antigens. Three of these antigens were identified: the filamentous actin (F-actin), the nucleic protein, RUVBL2, and the mitochondrial protein, HSPD1. Antibody titers to F-actin and HSPD1 were elevated in the plasma of PDAC patients, and also detectable in healthy donors. Thus, PCs in PDAC produce auto-antibodies reacting with intracellular self-antigens, which may result from promotion of pre-existing, autoreactive B cell responses. These observations indicate that the chronic inflammatory microenvironment of PDAC can support the adaptive immune response.
Monarchs sabotage milkweed to acquire toxins, not to disarm plant defence
Authors: Betz Anja , Bischoff Robert , Petschenka Georg 
Published: March 2023

AbstractSabotaging milkweed by monarch caterpillars is a textbook example for disarming plant defence. By severing leaf veins, monarchs are thought to prevent toxic latex flow to their feeding site. Here we show that sabotaging by monarch caterpillars is not an avoidance strategy. Instead, caterpillars actively ingest outflowing latex to increase sequestration of toxic latex cardenolides. Comparisons with caterpillars of the related non-sequestering common crow butterfly revealed three lines of evidence supporting our hypothesis. First, monarchs sabotage inconsistently and therefore the behaviour is not mandatory to feed on milkweed, while sabotaging in crows precedes every feeding event. Second, monarchs eagerly drink latex, while crow caterpillars spit out latex during sabotaging. Third, monarchs raised on detached leaves sequestered more cardenolides when latex was supplemented artificially. Hence, we conclude, that monarchs converted the “sabotage to avoid” strategy of their relatives into a “sabotage to consume” strategy for acquiring toxins for defence.
Widespread readthrough events in plants reveal unprecedented plasticity of stop codons
Authors: Zhang Yuqian , Li Hehuan , Shen Yanting , Wang Shunxi , Tian Lei , Yin Haoqiang , Shi Jiawei , Xing Anqi , Zhang Jinghua , Ali Usman , Sami Abdul , Chen Xueyan , Gao Chenxuan , Zhao Yangtao , Lyu Yajing , Wang Xiaoxu , Chen Yanhui , Tian Zhixi , Wu Shu-Biao , Wu Liuji 
Published: March 2023

AbstractStop codon readthrough (SCR), the decoding of a stop codon as a sense codon by the ribosome, has important biological implications but remains largely uncharacterized in plants. Here, we identified 1,009 SCR events in two monocots (maize, rice) and two dicots (soybean,Arabidopsis) using a proteogenomic strategy with 80 customized databases. SCR transcripts were mostly significantly shorter and had fewer components than non-SCR transcripts in two monocot plants, although these differences were not as significant in the dicots. Mass spectrometry evidence revealed that all three stop codons involved in SCR events could be recoded as 20 standard amino acids, some of which were also supported by suppressor transfer RNA analysis. In addition, we observed multiple functional signals in the C-terminal extensions of 34 maize SCR proteins, and characterized the structural and subcellular localization changes in the extended protein of BASIC TRANSCRIPTION FACTOR 3. Overall, our study not only demonstrates that SCR events are widespread in plants but also reveals the unprecedented recoding plasticity of stop codons, which provides important new insights into the flexibility of genetic decoding.
Environmental variables and species traits as drivers of wild bee pollination in intensive agroecosystems -a metabarcoding approach
Authors: Querejeta Marina , Marchal Lorène , Pfeiffer Paul , Roncoroni Marilyn , Bretagnolle Vincent , Gaba Sabrina , Boyer Stéphane 
Published: March 2023

AbstractWild bees are known to be efficient pollinators of wild plants and cultivated crops and they are essential ecosystem service providers. However, wild bee populations have been suffering from significant declines in the last decades mainly due to the use of agrochemicals. Within this framework, we aimed to characterize wild bees pollination spectrum (i.e. the community of pollinated flowering plants) in intensive agroecosystems, and describe the environmental variables and wild bee species traits influencing the pollination. To do this, we conducted metabarcoding analyses of pollen loads from wild bees collected in sunflower crops in the French region of Nouvelle-Aquitaine. Our study revealed that wild bees visited flowering plants corresponding to 231 different Operational Taxonomic Units, classified in 38 families of which Asteraceae, Brassicaceae and Apiaceae were the most visited and more than 90% of the visited taxa turned out to be wild flowers. We also analysed the potential effect of environmental variables and wild bee species traits in governing their choice of pollinated plants. The community composition of pollinated plants varied depending on the flowering stages of the sunflower and the farming system. Our results also show that pollination niche breadth (alpha diversity) varied depending on the flowering stages of the sunflower but was not different between organic and conventional farming systems.Regarding wild bee species traits, the community composition of pollinated plants varied in relation to wild bees body sizes and, sociality levels. Our results are consistent with previous studies, suggesting that solitary bees are more specialists when it comes to flower selection than social bees, which are more generalist. The metabarcoding of pollen loads enabled us to draw a global picture of plant-wild bee interactions in an intensive agroecosystem. Our findings support the hypothesis that a higher diversity of weeds may increase wild bee diversity in intensive agroecosystems.
Validity of the cell-extracted proteome as a substrate pool for exploring phosphorylation motifs of kinases
Authors: Niinae Tomoya , Sugiyama Naoyuki , Ishihama Yasushi 
Published: March 2023

AbstractThree representative protein kinases with different substrate preferences, ERK1 (Pro-directed), CK2 (acidophilic), and PKA (basophilic), were used to investigate phosphorylation sequence motifs in substrate pools consisting of the proteomes from three different cell lines, MCF7 (human mammary carcinoma), HeLa (human cervical carcinoma), and Jurkat (human acute T-cell leukemia). Specifically, recombinant kinases were added to the cell-extracted proteomes to phosphorylate the substratesin vitro. After trypsin digestion, the phosphopeptides were enriched and subjected to nanoLC/MS/MS analysis to identify their phosphorylation sites on a large scale. By analyzing the obtained phosphorylation sites and their surrounding sequences, phosphorylation motifs were extracted for each kinase-substrate proteome pair. We found that each kinase exhibited the same set of phosphorylation motifs, independently of the substrate pool proteome. Furthermore, the identified motifs were also consistent with those found using a completely randomized peptide library. These results indicate that cell-extracted proteomes can provide kinase phosphorylation motifs with sufficient accuracy, even though their sequences are not completely random, supporting the robustness of phosphorylation motif identification based on phosphoproteome analysis of cell extracts as a substrate pool for a kinase of interest.
Investigation of acute encephalitis syndrome with implementation of metagenomic next generation sequencing in Nepal
Authors: Shrestha R , Katuwal N , Tamrakar D , Tato CM , Vanaerschot M , Ahyong V , Gil J , Madhup SK , Gupta BP , Jha R 
Published: March 2023

AbstractBackgroundThe causative agents of Acute Encephalitis Syndrome remain unknown in 68-75% of the cases. In Nepal, the cases are tested only for Japanese encephalitis, which constitutes only about 15% of the cases. However, there could be several organisms, including vaccine-preventable etiologies that cause acute encephalitis, when identified could direct public health efforts for prevention, including addressing gaps in vaccine coverage.ObjectivesThis study employs metagenomic next-generation-sequencing in the exploration of infectious etiologies contributing to acute encephalitis syndrome in Nepal.MethodsIn this study, we investigated 90, Japanese-encephalitis-negative, banked cerebrospinal fluid samples that were collected as part of a national surveillance network in 2016 and 2017. Randomisation was done to include three age groups (<5-years; 5-14-years; >15-years). Only some metadata (age and gender) were available. The investigation was performed in two batches which included total nucleic-acid extraction, followed by individual library preparation (DNA and RNA) and sequencing on Illumina iSeq100. The genomic data were interpreted using Chan-Zuckerberg-ID and confirmed with polymerase-chain-reaction.ResultsHuman-alphaherpesvirus-2 and Enterovirus-B were seen in two samples. These hits were confirmed by qPCR and semi-nested PCR respectively. Most of the other samples were marred by low abundance of pathogen, possible freeze-thaw cycles, lack of process controls and associated clinical metadata.ConclusionFrom this study, two documented causative agents were revealed through metagenomic next-generation-sequencing. Insufficiency of clinical metadata, process controls, low pathogen abundance and absence of standard procedures to collect and store samples in nucleic-acid protectants could have impeded the study and incorporated ambiguity while correlating the identified hits to infection. Therefore, there is need of standardized procedures for sample collection, inclusion of process controls and clinical metadata. Despite challenging conditions, this study highlights the usefulness of mNGS to investigate diseases with unknown etiologies and guide development of adequate clinical-management-algorithms and outbreak investigations in Nepal.
Axonal damage and astrocytosis are biological correlates of grey matter network integrity loss: a cohort study in autosomal dominant Alzheimer disease
Authors: Vermunt L. , Sutphen C. , Dicks E. , de Leeuw D.M. , Allegri R. , Berman S.B. , Cash D.M. , Chhatwal J.P. , Cruchaga C. , Day G. , Ewers M. , Farlow M. , Fox N.C. , Ghetti B. , Graff-Radford N. , Hassenstab J. , Jucker M. , Karch C M. , Kuhle J. , Laske C. , Levin J. , Masters C.L , McDade E. , Mori H. , Morris J.C. , Perrin R.J. , Preische O. , Schofield P.R. , Suárez-Calvet M. , Xiong C. , Scheltens P. , Teunissen C.E. , Visser P.J. , Bateman R.J. , Benzinger T.L.S. , Fagan A.M. , Gordon B.A. , Tijms B.M. 
Published: March 2023

AbstractBrain development and maturation leads to grey matter networks that can be measured using magnetic resonance imaging. Network integrity is an indicator of information processing capacity which declines in neurodegenerative disorders such as Alzheimer disease (AD). The biological mechanisms causing this loss of network integrity remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and network integrity in mutation carriers (N=219) and noncarriers (N=136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Aβ, Tau, synaptic (SNAP-25, neurogranin) and neuronal calcium-sensor protein (VILIP-1) preceded grey matter network disruptions by several years, while inflammation related (YKL-40) and axonal injury (NfL) abnormalities co-occurred and correlated with network integrity. This suggests that axonal loss and inflammation play a role in structural grey matter network changes.Key points-Abnormal levels of fluid markers for neuronal damage and inflammatory processes in CSF are associated with grey matter network disruptions.-The strongest association was with NfL, suggesting that axonal loss may contribute to disrupted network organization as observed in AD.-Tracking biomarker trajectories over the disease course, changes in CSF biomarkers generally precede changes in brain networks by several years.
Neck pain, dry eye and Sjögren’s syndrome in Latin American students during the first wave of COVID-19: Frequencies and associated factors
Authors: Mejia Christian R. , Gutarra-Laureano Briggitte , Zorrilla-Lizana Ingrid L. , Arias-Chavez Dennis , Fernandez Maria F. , Vera Claudia A. , Vilela-Estrada Martin A. , Serna-Alarcón Victor , Requena Tatiana , Zambrano Lysien Ivania , Turcios Eleonora Espinoza 
Published: March 2023

AbstractIntroductionVirtual classes brought many changes to the lives of students, not only the fact of being more exposed to screens, but also because of the repercussions.AimTo determine the factors associated with suffering from neck pain, dry eye and Sjögren’s syndrome in students in Latin America during the first wave of COVID-19.MethodologyAnalytical cross-sectional study, using the COM and DEQ-5 scales, neck pain and dry eye/Sjögren’s syndrome, respectively, were measured; socio-educational variables were associated with them.DiscussionOf the 3939 students, those who lived in Panama, Chile and Bolivia were the ones who suffered the most from these pathologies. These pathologies were associated with the greater number of hours of computer use (all values p<0,001) and sex (all values p<0,002), medical students had more frequent dry eye and Sjögren’s syndrome (both p<0,031), Graduate students had more neck pain (p<0.001), but college students had less dry eye (p=0.025) and those at private universities had more neck pain (p=0.024).DiscussionImportant results of these three pathologies were found, this serves so that students can be evaluated in depth in each university, for a specialized diagnosis and try to avoid medium and long-term consequences for the constant use of electronic devices.ConclusionNeck pain, dry eye and Sjögren’s syndrome in students were associated with more hours of computer use and female sex, medical students had more frequent dry eye and Sjögren’s syndrome, graduate students had more neck pain, university students had less dry eye and those from private universities had more neck pain.
Patient-specific multi-modal modeling uncovers neurotransmitter receptor involvement in motor and non-motor axes of Parkinson’s disease
Authors: Khan Ahmed Faraz , Adewale Quadri , Lin Sue-Jin , Baumeister Tobias R. , Zeighami Yashar , Carbonell Felix , Palomero-Gallagher Nicola , Iturria-Medina Yasser 
Published: March 2023

AbstractMulti-systemic neurodegeneration in Parkinson’s disease (PD) is increasingly acknowledged, involving several neurotransmitter systems beyond the classical dopaminergic circuit and resulting in heterogeneous motor and non-motor symptoms. Nevertheless, the mechanistic basis of neuropathological and symptomatic heterogeneity remains unclear. Here, we use patient-specific generative brain modeling to identify neurotransmitter receptor-mediated mechanisms involved in PD progression. Combining receptor maps with longitudinal neuroimaging (PPMI data), we detect a diverse set of receptors influencing gray matter atrophy, microstructural degeneration, and dendrite loss in PD. Importantly, identified receptor mechanisms correlate with symptomatic variability along two distinct axes, representing motor/psychomotor symptoms with large GABAergic contributions, and cholinergically-driven visuospatial dysfunction. Furthermore, we map cortical and subcortical regions where receptors exert significant influence on neurodegeneration. Our work constitutes the first personalized causal model linking the progression of multi-factorial brain reorganization in PD across spatial scales, including molecular systems, accumulation of neuropathology in macroscopic brain regions, and clinical phenotypes.
Associations of weather and air pollution with objective physical activity and sedentary time before and after bariatric surgery: a secondary analysis of a prospective cohort study
Authors: Baillot Aurélie , Bernard Paquito , Jmii Nejm Eddine , Thomas J. Graham , Schumacher Leah M. , Papasavas Pavlos K. , Vithiananthan Sivamainthan , Jones Daniel , Bond Dale S. 
Published: March 2023

AbstractBackgroundMost metabolic and bariatric surgery (MBS) patients perform too little moderate-to-vigorous intensity physical activity (MVPA) and too much sedentary time (ST). Identifying factors that influence MVPA and ST in MBS patients is necessary to inform the development of interventions to target these behaviors. Research has focused on individual-level factors and neglected those related to the physical environment (e.g., weather and pollution). These factors may be especially important considering rapid climate change and emerging data that suggest adverse effects of weather and pollution on physical activity are more severe in people with obesity.ObjectivesTo examine the associations of weather (maximal, average and Wet Bulb Globe Temperatures), and air pollution indices (air quality index [AQI]) with daily physical activity (PA) of both light (LPA) and MVPA and ST before and after MBS.MethodsParticipants (n=77) wore an accelerometer at pre- and 3, 6, and 12-months post-MBS to assess LPA/MVPA/ST (min/d). These data were combined with participants’ local (Boston, MA or Providence, RI, USA) daily weather and AQI data (extracted from federal weather and environmental websites).ResultsMultilevel generalized additive models showed inverted U-shaped associations between weather indices and MVPA (R2≥ .63, p<.001), with a marked reduction in MVPA for daily maximal temperatures ≥20°C. Sensitivity analysis showed a less marked decrease of MVPA (min/d) during higher temperatures after versus before MBS. Both MVPA before and after MBS (R2=0.64, p<.001) and ST before MBS (R2=0.395; p≤.05) were negatively impacted by higher AQI levels.DiscussionThis study is the first to show that weather and air pollution indices are related to variability in activity behaviors, particularly MVPA, during pre- and post-MBS. Weather/environmental conditions should be considered in MVPA prescription/strategies for MBS patients, especially in the context of climate change.
Identification and characterization of two CRISPR-Cas systems associated with the mosquito microbiome
Authors: Hegde Shivanand , Rauch Hallie E. , Hughes Grant L. , Shariat Nikki 
Published: March 2023

AbstractThe microbiome profoundly influences many traits in medically relevant vectors such as mosquitoes, and a greater functional understanding of host-microbe interactions may be exploited for novel microbial-based approaches to control mosquito-borne disease. Here, we characterized two CRISPR-Cas systems in a novel bacterium,SerratiaSp. Ag1, that was isolated from the gut of anAnopheles gambiaemosquito. Two distinct CRISPR-Cas systems were identified inSerratiaAg1, CRISPR1 and CRISPR2. Based oncasgene composition, CRISPR1 is classified as a Type I-E CRISPR-Cas system and has a single array, CRISPR1. CRISPR2 is a Type I-F system with two arrays, CRISPR2.1 and CRISPR2.2. RT-PCR analyses show that allcasgenes from both systems are expressed during logarithmic growth in culture media. The direct repeat sequence of CRISPRs 2.1 and 2.2 are identical and found in the arrays of otherSerratiaspp, includingS. marcescensandS. fonticola, whereas CRISPR1 was not. We searched for potential spacer targets and revealed an interesting difference between the two systems: only 9% of CRISPR1 (Type I-E) targets are in phage sequences and 91% are in plasmid sequences. Conversely, ~66% of CRISPR2 (Type I-F), targets are found within phage genomes. Our results highlight the presence of CRISPR loci in gut-associated bacteria of mosquitoes and indicate interplay between symbionts and invasive mobile genetic elements over evolutionary time.Data SummaryThere is no supporting external data generated for this work.
Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via CASM
Authors: Cross Jake , Durgan Joanne , McEwan David G , Florey Oliver 
Published: March 2023

AbstractCells harness multiple pathways to maintain lysosome integrity, a central homeostatic process. Damaged lysosomes can be repaired, or targeted for degradation by lysophagy, a selective autophagy process involving ATG8/LC3. Here, we describe a parallel ATG8/LC3 response to lysosome damage, mechanistically distinct from lysophagy. Using a comprehensive series of biochemical, pharmacological and genetic approaches, we show that lysosome damage induces rapidConjugation ofATG8s toSingleMembranes (CASM). ATG8 proteins are recruited directly onto damaged membranes, independently of ATG13/WIPI2, and conjugated to PS, as well as PE, a molecular hallmark of CASM. Lysosome damage drives V-ATPase V0-V1 association, and direct recruitment of ATG16L1, dependent on K490 (WD40-domain), and sensitive toSalmonellaSopF. Lysosome damage-induced CASM is associated with the formation of dynamic LC3A-positive tubules, and promotes robust LC3A engagement with ATG2, a lipid transfer protein central to lysosome repair. Together, our data identify direct ATG8 conjugation as a rapid response to lysosome damage, with important links to lipid transfer and dynamics.