bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of Resistant Mutations against Upcoming ALK-TKIs, Repotrectinib (TPX-0005) and Ensartinib (X-396)
Authors: Doi Yuta , Tagaya Hiroaki , Noge Ayaka , Semba Kentaro 
Published: May 2022

AbstractALK gene rearrangement is observed in approximately 4% of patients with non-small cell lung cancer. These individuals benefit clinically from a range of approved ALK-TKIs; however, using many ALK-TKIs in a row will always result in resistant compound mutations in the kinase domain. Therefore, next-generation ALK-TKIs which are potent to these resistant mutations are still under development. In this context, preclinical prediction of resistant mutations generated by developing ALK-TKIs will provide useful information about the effective sequential treatment of ALK-TKIs. In this study, we developed a simple error-prone PCR-based mutation prediction system, and as a model study, we predicted resistant mutations against upcoming ALK-TKI, repotrectinib, and ensartinib. According to the predictive mutation patterns, repotrectinib and ensartinib may be used as second-line therapeutic options following the first-line alectinib treatment.
Perfect adaptation achieved by transport limitations governs the inorganic phosphate response in S. cerevisiae
Authors: Yip Hon Ming , Cheng Shiyu , Olson Evan J. , Crone Michael , Maerkl Sebastian J. 
Published: May 2022

AbstractCells cope with and adapt to ever-changing environmental conditions. Sophisticated regulatory networks allow cells to adjust to these fluctuating environments. One such archetypal system is theS. cerevisiaePho regulon. When external inorganic phosphate (Pi) concentration is low, the Pho regulon activates, expressing genes that scavenge external and internalPi. However, the precise mechanism controlling this regulon remains elusive. We conducted a systems analysis of the Pho regulon on the single cell level under well-controlled environmental conditions. This analysis identified a robust, perfectly adapted Pho regulon state in intermediatePiconditions, and we discovered a hitherto unknown intermediate nuclear localization state of the transcriptional master regulator Pho4p. The existence of an intermediate nuclear Pho4p state unifies and resolves outstanding incongruities associated with the Pho regulon, explains the observed programmatic states of the Pho regulon, and improves our general understanding of how nature evolves and controls sophisticated gene regulatory networks. We further propose that robustness and perfect adaptation are not achieved through complex network-centric control, but by simple transport biophysics. The ubiquity of multi-transporter systems suggests that similar mechanisms could govern the function of other regulatory networks as well.
Specific Pupylation as IDEntity Reporter (SPIDER) for the identification of Protein-Biomolecule interactions
Authors: Jiang He-Wei , Chen Hong , Zheng Yun-Xiao , Wang Xue-Ning , Meng Qingfeng , Xie Jin , Zhang Jiong , Zhang ChangSheng , Xu Zhao-Wei , Chen ZiQing , Wang Lei , Kong Wei-Sha , Zhou Kuan , Ma Ming-Liang , Zhang Hai-Nan , Guo Shu-Juan , Xue Jun-Biao , Hou Jing-Li , Liu Zhe-Yi , Niu Wen-Xue , Wang Fang-Jun , Wang Tao , Li Wei , Wang Rui-Na , Dang Yong-Jun , Czajkowsky Daniel M. , Qiao Yu , Dong Jia-Jia , Pei JianFeng , Tao Sheng-Ce 
Published: May 2022

AbstractProtein-biomolecule interactions play pivotal roles in almost all biological processes, the identification of the interacting protein is essential. By combining a substrate-based proximity labelling activity from the pupylation pathway of Mycobacterium tuberculosis, and the streptavidin (SA)-biotin system, we developed Specific Pupylation as IDEntity Reporter (SPIDER) for identifying protein-biomolecular interactions. As a proof of principle, SPIDER was successfully applied for global identification of interacting proteins, including substrates for enzyme (CobB), the readers of m6A, the protein interactome of mRNA, and the target proteins of drug (lenalidomide). In addition, by SPIDER, we identified SARS-CoV-2 Omicron variant specific receptors on cell membrane and performed in-depth analysis for one candidate, Protein-g. These potential receptors could explain the differences between the Omicron variant and the Prototype strain, and further serve as target for combating the Omicron variant. Overall, we provide a robust technology which is applicable for a wide-range of protein-biomolecular interaction studies.
Baculovirusbv/odv-e26is required for host behavioral manipulation by optimizing viral virulence to lepidopteran hosts
Authors: Hikida Hiroyuki , Katsuma Susumu 
Published: May 2022

AbstractHost behavioral manipulation is a widely used strategy for parasites to enhance their transmission. Lepidopteran nucleopolyhedroviruses (NPVs) induce hyperactivity and alteration of behavioral patterns in host insect larvae. Previous studies revealed thatBombyx mori nucleopolyhedrovirus(BmNPV) does not induce hyperactivity in larvalBombyx mori, whenBm8, a homologue of the baculovirusbv/odv-e26gene, is knocked out.Bm8knockout also enhances pathogenicity, but the relationship betweenBm8functions and host behavioral manipulation is still unknown. This study revealed thatBm8is dispensable for altering behavioral patterns but crucial for inducing hyperactivity.Bm8overexpression decreased pathogenicity inB. morilarvae and delayed viral infection in cultured cells. These results suggest thatBm8maintains larval locomotory activity and synchronizes hyperactivity induction with behavioral pattern alteration by suppressing viral virulence. Conserved amino acid residues were also identified in the coiled-coil domain of the Bm8 protein, which is required for suppressing viral virulence in cultured cells and larval hosts. Althoughbv/odv-e26is previously thought to be conserved in a limited group of lepidopteran NPVs, our synteny-based bioinformatics approach discovered putative homologues in the genomes of most lepidopteran NPVs. Functional analyses revealed that phylogenetically close and distantbv/odv-e26homologues possess suppressive activity with functionally essential common residues in their coiled-coil domains. Collectively, these findings indicate that baculovirusbv/odv-e26is a conserved gene optimizing viral virulence for establishing behavioral manipulation in NPV-infected larval hosts.Author SummaryBaculovirus-induced host abnormal behavior has been described in various lepidopteran insects for a long time, although it is still largely unknown how the virus establishes this complex trait. We showed that baculovirusbv/odv-e26is a factor that suppresses viral virulence and synchronizes hyperactivity and behavioral pattern alteration. We also revealed that putativebv/odv-e26homologues are encoded by a wider range of baculoviruses than previously thought, with functionally conserved residues. We confirmed the suppressive function in both phylogenetically close and distantbv/odv-e26homologues. These results indicate that acquiring a suppressive factor for viral virulence is a crucial event for the evolution of a host manipulation strategy by baculoviruses.
Landscape scale ecology of Tetracladium spp. fungal root endophytes
Authors: Lazar Anna , Mushinski Ryan M. , Bending Gary D. 
Published: May 2022

AbstractBackgroundThe genus Tetracladium has been traditionally regarded as an Ingoldian fungus or aquatic hyphomycete – a group of phylogenetically diverse, polyphyletic fungi which grow on decaying leaves and plant litter in streams. Recent sequencing evidence has shown that Tetracladium spp. may also exist as root endophytes in terrestrial environments, and furthermore may have beneficial effects on the health and growth of their host. However, the diversity of Tetracladium spp. communities in terrestrial systems and the factors which shape their distribution are largely unknown.ResultsUsing a fungal community internal transcribed spacer amplicon dataset from 37 UK Brassica napus fields we found that soils contained diverse Tetracladium spp., most of which represent previously uncharacterised clades. The two most abundant OTUs, related to previously described aquatic T. furcatum and T. maxilliforme, were enriched in roots relative to bulk and rhizosphere soil. For both taxa, relative abundance in roots, but not rhizosphere or bulk soil was correlated with B. napus yield. The relative abundance of T. furcatum and T. maxilliforme OTUs across compartments showed very similar responses with respect to agricultural management practices and soil characteristics. The factors shaping the relative abundance of T. furcatum and T. maxilliforme OTUs in roots was assessed using linear regression and structural equation modelling. Relative abundance of Tetracladium maxilliforme and Tetracladium furcatum in roots increased with pH, concentrations of phosphorus, and increased rotation frequency of OSR. While it decreased with increased soil water content, concentrations of extractable phosphorus, chromium, and iron.ConclusionsThe genus Tetracladium as a root colonising endophyte is a diverse and wildly distributed part of the oilseed rape microbiome that positively correlates to crop yield. The main drivers of its community composition are crop management practices and soil nutrients.
Pleiotropic fitness effects of the lncRNA Uhg4 in Drosophila melanogaster
Authors: MacPherson Rebecca A. , Shankar Vijay , Sunkara Lakshmi T. , Hannah Rachel C. , Campbell Marion R. , Anholt Robert R. H. , Mackay Trudy F. C. 
Published: May 2022

ABSTRACTLong noncoding RNAs (lncRNAs) are a diverse class of RNAs that are critical for gene regulation, DNA repair, and splicing, and have been implicated in development, stress response, and cancer. However, the functions of many lncRNAs remain unknown. In Drosophila melanogaster, U snoRNA host gene 4 (Uhg4) encodes an antisense long noncoding RNA that is host to seven small nucleolar RNAs (snoRNAs). Uhg4 is expressed ubiquitously during development and in all adult tissues, with maximal expression in ovaries; however, it has no annotated function(s). Here, we used CRISPR-Cas9 germline gene editing to generate multiple deletions spanning the promoter region and first exon of Uhg4. Females showed arrested egg development and both males and females were sterile. In addition, Uhg4 deletion mutants showed delayed development and decreased viability, and changes in sleep and responses to stress. Whole-genome RNA sequencing of Uhg4 deletion flies and their controls identified co-regulated genes and genetic interaction networks associated with Uhg4. Gene ontology analyses highlighted a broad spectrum of biological processes, including regulation of transcription and translation, morphogenesis, and stress response. Thus, Uhg4 is a lncRNA essential for reproduction with pleiotropic effects on multiple fitness traits.
Pseudomonas aeruginosacontracts mucus to form biofilms in tissue-engineered human airways
Authors: Rossy Tamara , Distler Tania , Pezoldt Joern , Kim Jaemin , Talà Lorenzo , Bouklas Nikolaos , Deplancke Bart , Persat Alexandre 
Published: May 2022

ABSTRACTThe opportunistic pathogenPseudomonas aeruginosacauses antibiotic-recalcitrant pneumonia by forming biofilms in the respiratory tract. Despite extensivein vitroexperimentation, howP. aeruginosaforms biofilms at the airway mucosa is unresolved. To investigate the process of biofilm formation in realistic conditions, we developed AirGels: 3D, optically-accessible tissue-engineered human lung models that emulate the airway mucosal environment. AirGels recapitulate important factors that mediate host-pathogen interactions including mucus secretion, flow and air-liquid interface, while accommodating high resolution live microscopy. With AirGels, we investigated the contributions of mucus toP. aeruginosabiofilm biogenesis inin vivo-like conditions. We found thatP. aeruginosaforms mucus-associated biofilms within hours by contracting luminal mucus early during colonization. Mucus contractions facilitates aggregation, thereby nucleating biofilms. We show thatP. aeruginosaactively contracts mucus using retractile filaments called type IV pili. Our results therefore suggest that, while protecting epithelia, mucus constitutes a breeding ground for biofilms.
Distinct cell states define the developmental trajectories of mucinous appendiceal neoplasms towards pseudomyxoma metastases
Authors: Ayala Carlos , Sathe Anuja , Bai Xiangqi , Grimes Susan M. , Shen Jeanne , Poultsides George A. , Lee Byrne , Ji Hanlee P. 
Published: May 2022

ABSTRACTAppendiceal mucinous neoplasms(AMN)are rare tumors of the gastrointestinal tract. They metastasize with widespread abdominal dissemination leading to pseudomyxoma peritonei(PMP), a disease with poor prognosis. The cellular features of origin, differentiation and progression in AMN and PMP remain largely unknown. We characterized the distinct cell states of AMN and PMP using single-cell RNA-sequencing in 31 samples including AMNs, PMP metastases and matched normal tissues. We identified previously undescribed cellular features and heterogeneity in AMN and PMP. We discovered developmental cell states in tumor epithelial cells that ranged from progenitor phase to goblet cell differentiation, which was accompanied by elevated mucin gene expression. Metastatic PMP cells had a distinct cell state with increased mTOR and RAS signaling pathways and a series of upregulated cancer genes. We observed heterogeneity in a single PMP tumor as well as PMP metastases from the same patient. We validated our findings with immunohistochemistry, mass spectrometry on malignant ascites from PMP patients and gene expression data from an independent set of 63 PMPs.
Substantial differences in soil viral community composition within and among four Northern California habitats
Authors: Durham Devyn M. , Sieradzki Ella T. , ter Horst Anneliek M. , Santos-Medellín Christian , Bess C. Winston A. , Geonczy Sara E. , Emerson Joanne B. 
Published: May 2022

AbstractViruses contribute to food web dynamics and nutrient cycles in diverse ecosystems, yet the biogeographical patterns that underlie these viral dynamics are poorly understood, particularly in soil. Here, we identified trends in soil viral community composition in relation to habitat, moisture content, and physical distance. We generated 30 soil viromes from four distinct habitats (wetlands, grasslands, woodlands, and chaparral) by selectively capturing virus-sized particles prior to DNA extraction, and we recovered 3,432 unique viral ‘species’ (vOTUs). Viral communities differed significantly by soil moisture content, with viral richness generally higher in wet compared to dry soil habitats. However, vOTUs were rarely shared between samples, including replicates <10 m apart, suggesting that soil viruses may not disperse well and that future soil viral community sampling strategies may need to account for extreme community differences over small spatial scales. Of the 19% of vOTUs detected in more than one sample, 93% were from the same habitat and site, suggesting greater viral community similarity in closer proximity and under similar environmental conditions. Within-habitat differences indicate that extensive sampling would be required for rigorous cross-habitat comparisons, and results belie emerging paradigms of higher viral activity in wet soils and soil viral community spatial heterogeneity.
Identification of a bile acid-binding transcription factor in Clostridioides difficile using chemical proteomics
Authors: Forster ER , Yang X , Hang HC , Shen A 
Published: May 2022

AbstractClostridioides difficile is a Gram-positive anaerobic bacterium that is the leading cause of hospital-acquired gastroenteritis in the US. In the gut milieu, C. difficile encounters microbiota-derived bile acids capable of inhibiting its growth, which are thought to be a mechanism of colonization resistance. While the levels of certain bile acids in the gut correlate with susceptibility to C. difficile infection, their molecular targets in C. difficile remain unknown. In this study, we sought to use chemical proteomics to identify bile acid-interacting proteins in C. difficile. Using photoaffinity bile acid probes and chemical proteomics, we identified a previously uncharacterized MerR family protein, CD3583 (now BapR), as a putative bile acid-sensing transcription regulator. Our data indicate that BapR binds and is stabilized by lithocholic acid (LCA) in C. difficile. Although loss of BapR did not affect C. difficile’s sensitivity to LCA, ΔbapR cells elongated more in the presence of LCA compared to wild-type cells. Transcriptomics revealed that BapR regulates the expression of the gene clusters mdeA-cd3573 and cd0618-cd0616, and cwpV, with the expression of the mdeA-cd3573 locus being specifically de-repressed in the presence of LCA in a BapR-dependent manner. Electrophoretic mobility shift assays revealed that BapR directly binds to the mdeA promoter region. Since mdeA is involved in amino acid-related sulfur metabolism and the mdeA-cd3573 locus encodes putative transporters, we propose that BapR senses a gastrointestinal tract-specific small molecule, LCA, as an environmental cue for metabolic adaptation.
Epidemiology and role of SARS-CoV-2 Linkage in Paediatric Inflammatory Multisystem Syndrome (PIMS): A Canadian Paediatric Surveillance Program National Prospective Study
Authors: Tal Tala El , Morin Marie-Paule , Morris Shaun K. , Farrar Daniel S. , Berard Roberta A , Kakkar Fatima , Hepburn Charlotte Moore , Baerg Krista , Beaufils Camille , Bennett Terri-Lyn , Benseler Susanne M , Beaudoin-Bussières Guillaume , Chan Kevin , Cyr Claude , Dahdah Nagib , Donner Elizabeth J. , Drouin Olivier , Edjoc Rojiemiahd , Eljaouhari Maryem , Embree Joanne E. , Farrell Catherine , Finzi Andrés , Forgie Sarah , Giroux Ryan , Kang Kristopher T. , King Melanie , Thibodeau Melanie Laffin , Lang Bianca , Laxer Ronald M. , Luu Thuy Mai , McCrindle Brian W. , Orkin Julia , Papenburg Jesse , Pound Catherine M. , Price Victoria E. , Proulx-Gauthier Jean-Philippe , Purewal Rupeena , Sadarangani Manish , Salvadori Marina l. , Thibeault Roseline , Top Karina A. , Viel-Thériault Isabelle , Haddad Elie , Scuccimarri Rosie , Yeung Rae S. M. 
Published: May 2022

AbstractBackgroundPaediatric inflammatory multisystem syndrome (PIMS) is a rare but serious condition temporally associated with SARS-CoV-2 infection. Using the Canadian Paediatric Surveillance Program (CPSP), a national surveillance system, we aimed to 1) study the impact of SARS-CoV-2 linkage on clinical and laboratory characteristics, and outcomes in hospitalized children with PIMS across Canada 2) identify risk factors for ICU admission, and 3) establish the minimum national incidence of hospitalizations due to PIMS and compare it to acute COVID-19.MethodsWeekly online case reporting was distributed to the CPSP network of more than 2800 pediatricians, from March 2020 to May 2021. Comparisons were made between cases with respect to SARS-CoV-2 linkage. Multivariable modified Poisson regression was used to identify risk factors for ICU admission and Minimum incidence proportions were calculated.FindingsIn total, 406 PIMS cases were analyzed, of whom 202 (49· 8%) had a positive SARS-CoV-2 linkage, 106 (26· 1%) had a negative linkage, and 98 (24· 1%) had an unknown linkage. The median age was 5· 4 years (IQR 2· 5–9· 8), 60% were male, and 83% had no identified comorbidities. Compared to cases with a negative SARS-CoV-2 linkage, children with a positive SARS-CoV-2 linkage were older (8· 1 years [IQR 4· 2–11· 9] vs. 4· 1 years [IQR 1· 7–7· 7]; p<0· 001), had more cardiac involvement (58· 8% vs. 37· 4%; p<0· 001), gastrointestinal symptoms (88· 6% vs. 63· 2%; p<0· 001), and shock (60· 9% vs. 16· 0%; p<0· 001). At–risk groups for ICU admission include children ≥ 6 years and those with a positive SARS-CoV-2 linkage. No deaths were reported. The minimum incidence of PIMS hospitalizations during the study period was 5· 6 hospitalizations per 100,000 population <18 years.InterpretationWhile PIMS is rare, almost 1 in 3 hospitalized children required ICU admission and respiratory/hemodynamic support, particularly those ≥ 6 years and with a positive SARS-CoV-2 linkage.FundingFinancial support for the CPSP was received from the Public Health Agency of Canada.
Association between Self-reported Masking Behavior and SARS-CoV-2 Infection Wanes from Pre-Delta to Omicron-Predominant Periods — North Carolina COVID-19 Community Research Partnership
Authors: Tjaden Ashley H. , Gibbs Michael , Runyon Michael , Weintraub William S. , Taylor Yhenneko J. , Edelstein Sharon L. ,   the COVID-19 Community Research Partnership Study Group
Published: May 2022

AbstractWe assessed the association between self-reported mask use during non-household interactions and COVID-19 infection during three pandemic periods. Odds of infection for those who did not always compared to those who always wore a mask was 66% higher during pre-Delta, 53% higher during Delta, declining to 16% higher during Omicron.
Predictive signs and symptoms of Bacterial Meningitis isolates in Northern Ghana
Authors: Weyori Enoch Weikem , Bernard Nkrumah , Abdul-Karim Abass , Eleeza John Bertson , Abubakari Braimah Baba , Kosi Abiwu Hilarius Asiwome , Eugene Kuugbee Dogkotenge , Yidaana Adadow , Ziblim Shamsu-Deen , Nuertey Benjamin , Weyori Benjamin Asubam , Yakubu Etowi Boye , Azure Stebleson , Abdul-Muizz Muktar , Cheba Valentine Koyiri , Kojo Adatsi Richard 
Published: May 2022

ABSTRACTBackgroundCerebrospinal meningitis (CSM) is a public health burden in Ghana that causes up to 10% mortality of the disease annually. About 20% of those who survive cerebrospinal meningitis suffer permanent sequelae. The study sought to understand the predictive signs and symptoms of bacterial meningitis implicated in its outcomes.MethodRetrospective data from the Public Health Division, Ghana Health Service on bacterial meningitis from 2015 to 2019 used for this study. A pre-tested data extraction form was used to collect patients’ information from case-based forms kept at the Disease Control Unit from 2015 to 2019. Data were transcribed from the case-based forms into a pre-designed Microsoft Excel template. The data was cleaned and imported into SPSS version 26 for analysis.ResultsBetween 2015-2019, a total of 2,446 CSM cases were reported. Out of these, 842 were confirmed. Among the confirmed cases, males constituted 55.3%. Children below 14 years of age were most affected (51.4%). The pathogens commonly responsible for bacterial meningitis wereNeisseria meningitidisandStreptococcus pneumoniaewith their respective strains especiallyNm W135, Nm X, Spn St. 1, andSpn St. 12F/12A/12B/44/4being responsible for most of the confirmed cases. The most predictive sign and symptom for bacterial meningitis was fever (X2=5.738a;p <0.05; AOR=1.303). Identified signs that were associated but less likely to cause disease were abdominal pain (X2=12.038a;p <0.05; AOR=0.597), neck stiffness (X2=6.447a;p <0.05; AOR=0.788), altered consciousness (X2=15.438a;p <0.05; AOR=0.673), and convulsion (X2=15.084a;p <0.05; AOR=0.678).ConclusionThe confirmed cases of bacterial meningitis from 2015 to 2019 had fever as the main predictive symptom. It is therefore noticed that abdominal pain, neck stiffness, altered consciousness and convulsion did not associate with CSM within the study period.