bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of biobased, biodegradable non-woven straw mats for multiple environmentally friendly uses
Authors: Gressel Jonathan , Hoffmann Sigal 
Published: August 2024

AbstractTwo billion tons of grains straws are produced annually, most of which has a negative ecological value. A small proportion is fed to ruminants as a low calory roughage. Grain straws had been burnt to prevent pathogen spores from over-wintering, now requiring greater fungicide use if left on soil surface, or more fertilizer use when the straw is plowed under and then binds nutrients. Lignin from paper making had been dumped, but is now finding limited uses, including as a glue in plywood manufacture. We propose to find the right ratio of lignin and other biodegradable adhesives coated on straw along with ascertaining the optimal pressures and temperatures for binding the adhesives and them cross-link straw fibers into mats.These slowly-biodegradable mats can be as: 1. Filters surrounding fish pens, binding pollutants from fish excrements, which are metabolized along with the straw by periphyton into material edible by fish as well as zooplankton eaten by fish. These filter mats may also prevent the movement of parasites into or out of the pens; 2. Mats used for erosion control on bare slopes until vegetated; 3. As insulation material in construction, where the carbon will be sequestered for decades; 4. As a compostable packaging material replacing polystyrene and bubble wrap; 5. Weed-preventing soil covering in organic and conventional agriculture. Such mats can be doped with ammonium and potassium as well as calcium and magnesium to be slowly released as fertilizer. Thus, by combining a negative environmental value waste materials with an adhesive we can generate mats that have very positive environmental benefits.
PneumoBrowse 2: An integrated visual platform for curated genome annotation and multiomics data analysis ofStreptococcus pneumoniae
Authors: Janssen Axel B. , Gibson Paddy S. , Bravo Afonso M. , de Bakker Vincent , Slager Jelle , Veening Jan-Willem 
Published: August 2024

AbstractStreptococcus pneumoniaeis an opportunistic human pathogen responsible for high morbidity and mortality rates. Extensive genome sequencing revealed its large pangenome, serotype diversity, and provided insight into genome dynamics. However, functional genome analysis has lagged behind, as that requires detailed and time-consuming manual curation of genome annotations, and integration of genomic and phenotypic data. To remedy this, PneumoBrowse was presented in 2018; a user-friendly interactive online platform, which provided the detailed annotation of theS. pneumoniaeD39V genome, alongside transcriptomic data. Since 2018, many new studies onS. pneumoniaegenome biology and protein functioning have been performed. Here, we present PneumoBrowse 2 (https://veeninglab.com/pneumobrowse), fully rebuilt in JBrowse 2. We updated annotations for transcribed and transcriptional regulatory features in the D39V genome. We added genome-wide data tracks for high-resolution chromosome conformation capture (Hi-C) data, chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-Seq), ribosome profiling, CRISPRi-seq gene essentiality data and more. Additionally, we included 18 phylogenetically diverseS. pneumoniaegenomes and their annotations. By providing easy access to diverse high-quality genome annotations, and links to other databases (including UniProt and AlphaFold), PneumoBrowse 2 will further accelerate research and development into preventive and treatment strategies, through increased understanding of the pneumococcal genome.Graphical abstract
Cultivar-specific fungicide resistance emerges during a growing season in field populations ofZymoseptoria tritici
Authors: Talas Firas , Stapley Jessica , McDonald Bruce A. 
Published: August 2024

AbstractZymoseptoria triticicauses the most damaging wheat disease in Europe, septoria tritici blotch (STB). In Europe, STB is controlled mainly by fungicides and fungicide resistance is frequently reported. While fungicide resistance is thought to emerge mainly from standing genetic variation within field populations ofZ. tritici, few studies have attempted to quantify the degree of fungicide resistance occurring at the field scale and to measure changes in frequencies of resistant strains following fungicide applications during a single growing season. Even fewer studies have considered the effects of different wheat cultivars on the emergence of fungicide resistance. We measured EC50 values for 1005 strains ofZ. triticisampled at two time points from 17 different wheat cultivars growing in a replicated field experiment that was treated with combinations of five different fungicides three times during the growing season. We found that field populations ofZ. triticican maintain a very high diversity in fungicide sensitivity phenotypes despite three fungicide treatments, with as much diversity found within a single field during a single growing season as has been described across all of Europe over several years. Multidrug resistance to two or more fungicides was found in 18.9% of the tested strains. We discovered that wheat cultivars that were more resistant to STB tended to be colonized byZ. triticistrains that exhibited higher fungicide resistance. We also found that specific wheat cultivars selected for resistance to specific active ingredients. Overall, our findings illustrate the many challenges associated with designing fungicide treatment programs that aim to reduce selection for fungicide resistance when confronted with a pathogen likeZ. triticithat has a very high evolutionary potential.
Rapid Raman spectroscopy-based test for antimicrobial resistance
Authors: Mushenkov Vladimir , Zhigalova Ksenia , Denisov Pavel , Gordeev Alexey , Lukyanov Dmitry , Kukushkin Vladimir , Priputnevich Tatiana , Zavyalova Elena 
Published: August 2024

AbstractAntimicrobial resistance is one of the top global health threats. In 2019, antimicrobial resistance was associated with 4.95 million deaths, of which 1.97 million were caused by drug resistant infections directly. The main subset of AMR is the antibiotic resistance, that is resistance of bacteria to antibiotic treatment. Traditional and most commonly used antibiotic susceptibility tests are based on detection of bacterial growth and its inhibition in the presence of an antimicrobial. These tests typically take over 1-2 days to perform, so empirical therapy schemes are often administered before the proper testing. Rapid tests for antimicrobial resistance are necessary to optimize the treatment of bacterial infection. Here we combine MTT test with Raman spectroscopy to provide 1.5-hour long test for minimal inhibitory concentrations determination. SeveralE.coliandK.pneumoniaestrains were tested with three types antibiotics, including ampicillin from penicillin family, kanamycin from aminoglycoside family and levofloxacin from fluoroquinolone family. The test provided the same minimal inhibitory concentrations as traditional Etest confirming its robustness.
Discovery and Engineering of a New BvCas12a Nuclease for Mammalian Genome Editing and Nucleic Acid Detection
Authors: SHEN Xuechun , HUANG Lei , WANG Dan , LIU Chuan , CHEN Ke , LI Baitao , QI Chen , ZOU Yuanqiang , XIAO Liang , JIANG Yuan , LAN Hongxia , ZHENG Yue 
Published: August 2024

AbstractCas12a is an RNA-guided endonuclease that has emerged as a powerful gene-editing tool. We have identified a novel Cas protein, BvCas12a, fromButyricimonas virosawith a 5’-TYTN protospacer adjacent motif (PAM). BvCas12a exhibits double-stranded DNA cleavage activityin vitroand genome editing activity in eukaryotic cells. Though the editing efficiency of BvCas12a is marginally lower than that of AsCas12a, the editing specificity of BvCas12a in eukaryotic cells is comparable or superior to that of AsCas12a. Moreover, BvCas12a exhibits substantial collateral activity and can detect HPV DNA effectively and accurately in conjunction with isothermal amplification, highlighting its potential in nucleic acid diagnostics. Furthermore, we have engineered BvCas12a to create two variants, BvCas12a-R (N549R, T606P) and BvCas12a-RVR (N549R, K555V, C559R, T606P). These variants recognize expanded 5’-YYN and 5’-YN PAMin vitro, respectively. Additionally, they exhibit higher editing activity than wild-type BvCas12a and recognize 5’-YYN PAMin vivoat all sites detected. In conclusion, we have identified a novel BvCas12a protein with high specificity and engineered two variants with broader PAM compatibility and improved genome editing efficiency. These findings offer a potent gene editing tool for application in scientific research, gene therapy, and nucleic acid diagnostics.
Differential requirement of m6A reader proteins, IGF2BP2 and HNRNPA2B1 for the processing of N6-methyladenosine modified H19 lncRNA: Stability versus miR-675 biogenesis
Authors: Jana Samarjit , Chowdhury Abhishek , Somasundaram Kumaravel 
Published: August 2024

AbstractH19, a lnc-pri-miRNA that encodes miR-675, is dysregulated in numerous cancers. However, the specific mechanisms underlying H19 processing, particularly miR-675 formation, remain unclear. Our study reveals that H19 is highly expressed and m6A modified in a METTL3-dependent manner in glioblastoma (GBM) and glioma stem cells (GSCs). Silencing METTL3 reduced both H19 and miR-675 levels, whereas overexpressing METTL3 promoted miR-675 processing without affecting H19 levels. Further, miR-675 derived from exogenously expressed H19 was affected considerably more in METTL3 silenced glioma cells compared to H19 levels, suggesting differential requirements in the processing of m6A modified H19 transcript. We demonstrate that H19 interacts with m6A reader proteins, IGF2BP2 and HNRNPA2B1, and silencing either reduced H19 and miR-675 levels. However, a high level of miR-675 seen in METTL3 overexpressing cells is severely affected in HNRNPA2B1-silenced compared to IGF2BP2-silenced glioma cells. Interestingly, IGF2BP2 silencing more significantly affected H19 stability from exogenous H19 construct, while HNRNPA2B1 silencing severely impacted miR-675 processing. Site-directed mutagenesis confirmed the presence of two m6A sites in the first exon of H19, with site #1 facilitating HNRNPA2B1 interaction to promote miR-675 processing. In contrast, the IGF2BP2 interaction is promoted by site #2, resulting in enhanced H19 stability. H19-METTL3-HNRNPA2B1-miR675 axis inhibited Calneuron 1 (CALN1), a known target of miR-675, to promote glioma cell migration. Notably, a low CALN1/high H19 predicted a poor prognosis in GBM patients and was further exacerbated by a high METTL3 or HNRNPA2B1 but not IGF2BP2 transcript levels. Thus, we found that the H19 transcript is highly expressed in GBM and m6A modified, and the m6A reader proteins, IGF2BP2 and HNRNPA2B1, regulate the H19 processing differently to promote glioma cell migration.
Deep Visual Proteomics reveals DNA replication stress as a hallmark of Signet Ring Cell Carcinoma
Authors: Kabatnik Sonja , Zheng Xiang , Pappas Georgios , Steigerwald Sophia , Padula Matthew P , Mann Matthias 
Published: August 2024

AbstractSignet Ring Cell Carcinoma (SRCC) is a rare and highly malignant form of adenocarcinoma with increasing incidence and poor prognosis due to late diagnosis and limited treatment options. We employed Deep Visual Proteomics (DVP), which combines AI directed cell segmentation and classification with laser microdissection and ultra-high sensitivity mass spectrometry, for cell-type specific proteomic analysis of SRCC across the bladder, prostate, liver, and lymph nodes of a single patient. DVP identified significant alterations in DNA damage response (DDR) proteins, particularly within the ATR and mismatch repair (MMR) pathways, indicating replication stress as a crucial factor in SRCC mutagenicity. Additionally, we observed substantial enrichment of immune-related proteins, reflecting high levels of cytotoxic T lymphocyte infiltration and elevated PD-1 expression. These findings suggest that pembrolizumab immunotherapy may be more effective than conventional chemotherapy for this patient. Our results provide novel insights into the proteomic landscape of SRCC, identifying potential targets and open up for personalized therapeutic strategies in managing SRCC.
SNARE mimicry by the CD225 domain of IFITM3 enables regulation of homotypic late endosome fusion
Authors: Rahman Kazi , Wilt Isaiah , Jolley Abigail A. , Chowdhury Bhabadeb , Datta Siddhartha A. K. , Compton Alex A. 
Published: August 2024

AbstractThe CD225/Dispanins superfamily consists of membrane proteins that regulate vesicular transport and membrane fusion events driving neurotransmission, glucose transport, and antiviral immunity. However, how the CD225 domain controls membrane trafficking was unknown. We reveal that the CD225 domain contains a SNARE-like motif that enables interaction with cellular SNARE fusogens. Proline rich transmembrane protein 2 (PRRT2) encodes a SNARE-like motif that enables interaction with neuronal SNARE proteins, and mutations therein disrupt SNARE binding and are linked to neurological disease. Another CD225 member, interferon-induced transmembrane protein 3 (IFITM3), protects cells against Influenza A virus infection. IFITM3 interacts with SNARE proteins that mediate late endosome-late endosome (homotypic) fusion and late endosome-lysosome (heterotypic) fusion. IFITM3 binds to syntaxin 7 (STX7) in cells and in vitro, and mutations that abrogate STX7 binding cause loss of antiviral activity against Influenza A virus. Mechanistically, IFITM3 disrupts assembly of the SNARE complex controlling homotypic fusion and accelerates the trafficking of endosomal cargo to lysosomes. Our results suggest that SNARE modulation plays a previously unrecognized role in the diverse functions performed by CD225 proteins.
Cortical Representation of the Glottal Events during Speech Production
Authors: Veillette John P. , Rosen Jacob , Margoliash Daniel , Nusbaum Howard C. 
Published: August 2024

AbstractTo produce complex motor behaviors such as speech, the nervous system must accommodate the fact that sensory feedback is delayed relative to actual movements; by most accounts, this is accomplished using an internal model that predicts the current state of the body’s periphery from recent motor system output. Here we show that onsets of events in the human glottal waveform, measured via electroglottography, are encoded in the human electroencephalogram (EEG) during speech production, maximally reflected at zero time lag. Conversely, we show that glottal event times can be decoded from the EEG. Furthermore, after prolonged exposure to delayed auditory feedback, subjects show a robust recalibration of their behaviorally observed threshold for detecting auditory-motor mismatches, and decoding models that perform best in normal speaking conditions also showed a shift in the predicted times of glottal events relative to actual events. This suggests that decoding performance is driven by plastic internal representations of peripheral event timing (while ruling out movement artifact concerns). Our results provide a missing component for a mechanism to associate specific feedback events with the neurons that gave rise to those movements, mirroring the observation of synchronous bursting of songbird HVC neurons with events in the trajectories of the biophysical parameters that control bird voicing.
UFMylation suppresses Type I IFN signaling duringM. tuberculosisinfection of human macrophages
Authors: Garelis Nicholas E. , Luteijn Rutger D. , Raulet David H. , Cox Jeffery S. 
Published: August 2024

ABSTRACTType I Interferons (Type I IFNs) are critical for host defense against a wide range of viral infections but can enhance the pathogenicity of several bacterial pathogens, includingMycobacterium tuberculosis(Mtb)1–4. Given the significance of Type I IFN signaling in determining Mtb infection outcomes we sought to uncover new molecular mechanisms controlling Type I IFN activation during mycobacterial infection. We performed a genome-wide CRISPR interference screen in human macrophages to identify genes that regulate IFN-β, during infection withM. marinum (Mm). In addition to known regulators of Type I IFN, we identified UFL1, which encodes the E3 ligase for the ubiquitin-like protein UFM1, as a major regulator of IFN-β during mycobacterial infection. Depletion of other components of the UFMylation pathway, DDRGK1 and UFM1, also resulted in increased IFN-β, indicating that UFMylation activity is required for Type I IFN regulation. Deficiency in UFMylation resulted in increased production and secretion of IFN-β during macrophage infection with both Mm and Mtb compared to control cells. Additionally, silencing UFL1 resulted in increased expression of several interferon stimulated genes and other pro-inflammatory genes, including TNF and IL-6, at both the mRNA and protein level. Transcriptional profiling revealed a surprisingly broad increase in pro-inflammatory responses of UFL1-deficient cells during Mtb infection, particularly for interferon-stimulated genes. Our data reveals an unexpected role of the UFMylation pathway in suppressing Type I IFN, a pro-inflammatory immune pathway with detrimental effects on Mtb infection outcome.
Plasma glial fibrillary acidic protein and neurofilament light chain in behavioural variant frontotemporal dementia and primary psychiatric disorders
Authors: Eratne Dhamidhu , Kang Matthew JY , Lewis Courtney , Dang Christa , Malpas Charles , Ooi Suyi , Brodtmann Amy , Darby David , Zetterberg Henrik , Blennow Kaj , Berk Michael , Dean Olivia , Bousman Chad , Thomas Naveen , Everall Ian , Pantelis Chris , Wannan Cassandra , Cicognola Claudia , Hansson Oskar , Janelidze Shorena , Santillo Alexander F , Velakoulis Dennis ,   The MiND Study Group
Published: August 2024

ABSTRACTObjectiveTimely, accurate distinction between behavioural variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD) is a clinical challenge. Blood biomarkers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have shown promise. Prior work has shown NfL helps distinguish FTD from PPD. Few studies have assessed NfL together with GFAP.MethodsWe investigated plasma GFAP and NfL levels in participants with bvFTD, bipolar affective disorder (BPAD), major depressive disorder (MDD), treatment-resistant schizophrenia (TRS), healthy controls (HC), adjusting for age and sex. We compared ability of GFAP and NfL to distinguish bvFTD from PPD.ResultsPlasma GFAP levels were significantly (all p<0.001) elevated in bvFTD (n=22, mean (M)=273pg/mL) compared to BPAD (n=121, M=96pg/mL), MDD (n=42, M=105pg/mL), TRS (n=82, M=67.9pg/mL), and HC (n=120, M=76.8pg/mL). GFAP distinguished bvFTD from all PPD with an area under the curve (AUC) of 0.85, 95% confidence interval [0.76, 0.95]. The optimal cut-off of 105pg/mL was associated with 73% specificity and 86% sensitivity. NfL had AUC 0.95 [0.91, 0.99], 13.3pg/mL cut-off, 88% specificity, 86% sensitivity, and was superior to GFAP (p=0.02863) and combination of GFAP and NfL (p=0.04726).ConclusionsThis study found elevated GFAP levels in bvFTD compared to a large cohort of PPD, but NfL levels exhibited better performance in this distinction. These findings extend the literature on GFAP in bvFTD and build evidence for plasma NfL as a useful biomarker to assist with distinguishing bvFTD from PPD. Utilisation of NfL may improve timely and accurate diagnosis of bvFTD.
Mapping the genetic landscape of disorders on the autoimmune-autoinflammatory continuum: potential implications for classification and treatment
Authors: Fominykh Vera , Shadrin Alexey A. , Jaholkowski Piotr , Fuhrer Julian , Parker Nadine , Wiström Erik D. , Frei Oleksandr , Smeland Olav B. , Sanner Helga , Djurovic Srdjan , Andreassen Ole A. 
Published: August 2024

AbstractObjectivesBased on clinical, biomarker and genetic data, autoimmune and autoinflammatory disorders (AIDs) can be classified as a disease continuum from pure autoinflammatory to pure autoimmune with mixed diseases in between. However, the genetic architecture of AIDs has not been systematically described. Here we investigate the polygenic continuum of AIDs using genome-wide association studies (GWAS) and statistical genetics methods.MethodsWe mapped the genetic landscape of 15 AIDs using GWAS summary statistics and methods including genomic structural equation modelling (genomic SEM), linkage disequilibrium score regression, Local Analysis of [co]Variant Association, and Gaussian causal mixture modelling (MiXeR). We performed enrichment analyses of tissues and biological gene-sets using MAGMA.ResultsGenomic SEM suggested a continuum structure with four underlying latent factors from autoimmune diseases at one end to autoinflammatory on the opposite end. Across AIDs, we observed a balanced mixture of negative and positive local correlations within the major histocompatibility complex, while outside this region they were predominantly positive. MiXeR analysis showed large genetic overlap in accordance with the continuum landscape. MAGMA analysis implicated genes associated with monogenic immune diseases in autoimmune (factor 1) and autoinflammatory diseases (factor 4).ConclusionsOur findings support a polygenic continuum across AIDs, with four genetic clusters. The “polygenic autoimmune” and “polygenic autoinflammatory” clusters reside on margins of this continuum. The identified genetic patterns across different AIDs can potentially guide drug selection, as patients within the same clusters may benefit from the same therapies.
A metabolic constraint in the kynurenine pathway drives mucosal inflammation in IBD
Authors: Welz Lina , Harris Danielle MM , Kim Na-Mi , Alsaadi Abrar I , Wu Qicong , Oumari Mhmd , Taubenheim Jan , Volk Valery , Credido Graziella , Koncina Eric , Mukherjee Pranab K , Tran Florian , Sievers Laura Katharina , Pavlidis Polychronis , Powell Nick , Rieder Florian , Letellier Elisabeth , Waschina Silvio , Kaleta Christoph , Feuerhake Friedrich , Verstockt Bram , McReynolds Melanie R , Rosenstiel Philip , Schreiber Stefan , Aden Konrad 
Published: August 2024

SummaryInflammatory bowel disease (IBD) is associated with perturbed metabolism of the essential amino acid tryptophan (Trp). Whether increased degradation of Trp directly fuels mucosal inflammation or acts as a compensatory attempt to restore cellular energy levels viade-novonicotinamide adenine dinucleotide (NAD+) synthesis is not understood. Employing a systems medicine approach on longitudinal IBD therapy intervention cohorts and targeted screening in preclinical IBD models, we discover that steady increases in Trp levels upon therapy success coincide with a rewiring of metabolic processes within the kynurenine pathway (KP). In detail, we identify that Trp catabolism in IBD is metabolically constrained at the level of quinolinate phosphorybosyltransferase (QPRT), leading to accumulation of quinolinic acid (Quin) and a decrease of NAD+. We further demonstrate that Trp degradation along the KP occurs locally in the inflamed intestinal mucosa and critically depends on janus kinase / signal transducers and activators of transcription (JAK/STAT) signalling. Subsequently, knockdown ofQPRT in-vitroinduces NAD+depletion and a pro-inflammatory state, which can largely be rescued by bypassing QPRT via other NAD+precursors. We hence propose a model of impairedde-novoNAD+synthesis from Trp in IBD. These findings point towards the replenishment of NAD+precursors as a novel therapeutic pathway in IBD.