bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elongasome core proteins and class A PBP1a display zonal, processive movement at the midcell ofStreptococcus pneumoniae
Authors: Perez Amilcar J. , Lamanna Melissa M. , Bruce Kevin E. , Touraev Marc A. , Page Julia E. , Shaw Sidney L. , Tsui Ho-Ching Tiffany , Winkler Malcolm E. 
Published: January 2024

ABSTRACTOvoid-shaped bacteria, such asStreptococcus pneumoniae(pneumococcus), have two spatially separated peptidoglycan (PG) synthase nanomachines that locate zonally to the midcell of dividing cells. The septal PG synthase bPBP2x:FtsW closes the septum of dividing pneumococcal cells, whereas the elongasome located on the outer edge of the septal annulus synthesizes peripheral PG outward. We showed previously by sm-TIRFm that the septal PG synthase moves circumferentially at midcell, driven by PG synthesis and not by FtsZ treadmilling. The pneumococcal elongasome consists of the PG synthase bPBP2b:RodA, regulators MreC, MreD, and RodZ, but not MreB, and genetically associated proteins Class A aPBP1a and muramidase MpgA. Given its zonal location separate from FtsZ, it was of considerable interest to determine the dynamics of proteins in the pneumococcal elongasome. We found that bPBP2b, RodA, and MreC move circumferentially with the same velocities and durations at midcell, driven by PG synthesis. However, outside of the midcell zone, the majority of these elongasome proteins move diffusively over the entire surface of cells. Depletion of MreC resulted in loss of circumferential movement of bPBP2b, and bPBP2b and RodA require each other for localization and circumferential movement. Notably, a fraction of aPBP1a molecules also moved circumferentially at midcell with velocities similar to those of components of the core elongasome, but for shorter durations. Other aPBP1a molecules were static at midcell or diffusing over cell bodies. Last, MpgA displayed non-processive, subdiffusive motion that was largely confined to the midcell region and less frequently detected over the cell body.SIGNIFICANCEThis paper reports three types of single-molecule motions of PG synthesis proteins in the ovoid-shaped, pathogenic bacteriumStreptococcus pneumoniae, not reported previously in other bacteria. The core elongasome exhibits zonal, circumferential motion in the absence of MreB filaments, independent of FtsZ treadmilling or the processive movement of the septal PG synthase. Class A aPBP1a also moves processively at midcell, but is not a persistent component of the core elongasome. These types of motions have implications for the functions of these PG synthases and indicate that processive motion in pneumococcus follows spatially separate tracks, possibly reflective of PG structure. In contrast, the MpgA muramidase displays a different kind of subdiffusive motion that is largely confined to midcell by an unknown mechanism.
Effects of different feeding methods on serum biochemical indexes, metabolic indexes, immune indexes, and intestinal microorganisms of Nanjiang yellow goats
Authors: Luo Yangyang , Anwar Asma , Pan Cheng , Shi Hengbo , Mustafa Shehr Bano , Chen Yu , Zhang Zhenzhen , Li Jingjing , Zhu Jiangjiang , Zhao Wangsheng 
Published: January 2024

AbstractThe intestinal microbiota significantly influences the intake, storage, and absorption of nutrients in animals, thereby greatly impacting the growth and development of the animals. Factors such as diet, animal breed, growth stage, and feeding methods may affect variations in the composition of the intestinal microbiota. However, research on the variations in the intestinal microbiota and metabolites of Nanjiang Yellow goats under different feeding methods is still unclear. We measured various serum biochemical indicators and immune biochemical indicators and found that the triglyceride (TC) content in the grazing group (the FMMF) was significantly lower than in the barn-feeding group (the SSMF) (P<0.05). Serum levels of immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin G (IgM) were higher in the FMMF group. At the phylum level, the most abundant bacteria wereFirmicutes, Bacteroidota, andVerrucomicrobiota. At the genus level, the most abundant microbial groups wereChristensenellaceae_R-7_group, UCG-005, andRikenellaceae_RC9_gut_group. Differential metabolite enrichment analysis through KEGG pathways revealed that the most remarkably enriched pathway was “Metabolic pathways,” including Steroid hormone biosynthesis and Arachidonic acid metabolism, among others. Analyzed by multi-omics association, we identified notably different microbial features correlated with immune indicators and metabolites after different feeding methods. We observed a significant negative correlation (P<0.05) between the concentrations of serum immune factors interleukin-2 (IL-2), interleukin-4 (IL-4), andg__probable_genus_10. The concentration of IgM in serum showed a highly significant positive correlation (P<0.01) with the relative abundance ofg__Erysipelatoclostridiumin the intestine. Interestingly, most differential metabolites were significantly associated with intestinal microbiota. This experiment indicates that different feeding methods may influence the diversity and relative abundance of the intestinal microbiota in Nanjiang Yellow goats. The intestinal microbiota is correlated with immune indicators and metabolism, and regulating the diversity and relative abundance of the intestinal microbiota can be a way to adjust metabolism, thereby promoting the healthy growth of the Nanjiang Yellow goats.
Analysis of Dental Tissues Density in Healthy Children Based on Radiological Data
Authors: Aleksei Reshetnikov , Natalia Shaikhattarova , Margarita Mazurok , Nadezhda Kasatkina 
Published: January 2024

AbstractIntroductionThe information about the Hounsfield range values for healthy tooth tissues could become an additional tool in assessing dental health and could be used, among other data, for subsequent machine learning.AimThe aim of our study was to determine dental tissues density values in Hounsfield units.Materials and MethodsThe total selection included 36 healthy children (21 girls and 15 boys) with an age range of 6-10 to 11-15 years at the time of the study. The analysis of 320 teeth’s tissue density was carried out. The data were expressed as a mean and standard deviation. The significance was determined using the Student’s t-test. P-values less than 0.05 were considered significant.ResultsAnalysis of the data showed that the tissues of healthy teeth in children have different density ranges. Enamel: 2954.69±223.77 HU - 2071.00±222.86 HU; dentin: 1899.23±145.94 HU - 1323.10±201.67 HU; pulp: 420.29±196.47 HU -183.63±97.59 HU. No gender differences concerning the density of dental tissues were reliably identified.ConclusionThe evaluation of Hounsfield values for dental tissues can be used as an objective method for assessing their density. If the determined density values of the enamel, dentin, and pulp of the tooth do not correspond to the range of values for healthy tooth tissues, it may indicate a pathology.Key MessagesStudying the range of healthy and diseased dental tissues using Hounsfield scores, as well as standardizing studies, can help clinicians improve screening accuracy and optimize follow-up of the effectiveness of preventive and therapeutic interventions in the future.
Development of Int-Plex@ binary memory switch system: plant genome modulation driven by large serine-integrases
Authors: de Oliveira Marco Antônio , Lima Rayane Nunes , Florentino Lilian Hasegawa , Severo de Almeida Mariana Martins , Melo Fernando Lucas , Bonnet Raquel Vasquez , Lacorte Cristiano , Rech Elibio 
Published: January 2024

ABSTRACTThe comprehension of virus-host interactions has allowed numerous advances in developing biotechnological methodologies for plant genome editions, constituting a promising path for plant genetic engineering. Among these advancements, phage- encoded large serine-integrases have emerged as noteworthy tools to modulate plant metabolic pathways by inserting, excising, or inverting DNA stretches in a reversible and specific way. The present work shows the foundation of the Int-Plex@ (INTegrase PLant EXpression) binary memory switch system, which consists of the application of four distinct orthogonal prophage large serine-integrases (Int) (BxB1, phiC31, Int13, and Int9) as an input trigger mechanism for the inversion or excision of genomic DNA. The memory genetic switch is divided into the excision module and the inversion module. The excision module is activated by BxB1 or phiC31 enzymes (input). In this case, the DNA sequence flanked by its attachment sites is excised from the genome (output). The inversion module is activated by Int9 or Int13 (input). The invertedmgfgene sequence is flipped to its functional coding sequence, and the switch output is mGFP. Moreover, prokaryotic-based cell-freein vitrotranscription-translation reactions (TxTl) were used as a fast platform for testing IntsattB/P in tandemsite activity. Furthermore different plasmid delivery strategies for plant cell Int heterologous expression were tested: leaf tissue agroinfiltration ofAgrobacterium tumefacienstransformed with binary plasmids and a biolistic system. After each treatment, the edited genomic DNA sequences were amplified and verified by Sanger and Nanopore sequencing. Despite the challenges of using Ints, the potential benefits are significant and deserve deeper exploration and development. The Int-Plex@ binary genome memory switch system can be applied to produce genetic circuits combined with omics tools and sgRNAs to engineer and modulate plant metabolic pathways temporally and reversibly.
A robust set of qPCR methods to evaluate adulteration in major spices and herbs
Authors: Behr Marc , Garlant Linda , Pietretti Danilo , Pellegrin Clément , Lievens Antoon , Boix Sanfeliu Ana , Maquet Alain , Alvarellos Lourdes 
Published: January 2024

AbstractSpices and herbs are used in multiple forms by consumers and companies related to food or pharmaceuticals. Their intricate supply chains, high prices and limited productions make them susceptible to deceptive practises. However, robust methodology to detect multiple adulterants is still rarely available, preventing national control laboratories from enforcing European and national regulations.This article presents qPCR methods developed to identify adulterants in six commonly consumed spices and herbs, namely paprika, turmeric, saffron, cumin, oregano and black pepper. Each genuine sample was blended with the top five adulterants identified in the European Union-wide coordinated control plan on herbs and spices and existing literature. These SYBR™ Green qPCR methods enable specific detection of adulterants, and their sensitivities allow to differentiate inadvertent contamination from deliberate adulteration. Methods performances were evaluated both in binary mixtures and with complex adulteration pattern, validating their effectiveness in safeguarding the authenticity of these high values commodities.HighlightsAuthenticity of spices and herbs is at high risk of fraudulent malpractices.We provide specific qPCR methods to detect prevalent adulterants.Trueness of each method was systematically assessed.Sensitivity of methods meet ISO requirements for purity assessment.Methods versatility is evaluated with multi-adulterated samples.
Dual DNA/RNA-binding factor regulates dynamics of hnRNP splicing condensates
Authors: Ray Mukulika , Zaborowsky Julia , Mahableshwarkar Pranav , Vaidyanathan Smriti , Shum Jasmine , Viswanathan Renjith , Huang Annie , Wang Szu-Huan , Johnson Victoria , Wake Noah , Conard Ashley M. , Conicella Alexander E. , Puterbaugh Ryan , Fawzi Nicolas L. , Larschan Erica 
Published: January 2024

AbstractDespite decades of research, mechanisms by which co-transcriptional alternative splicing events are targeted to the correct genomic locations to drive cell fate decisions remain unknown. By combining structural and molecular approaches, we define a new mechanism by which an essential transcription factor (TF) targets co-transcriptional splicing through physical and functional interaction with RNA and RNA binding proteins (RBPs). We show that an essential TF co-transcriptionally regulates sex-specific alternative splicing by directly interacting with a subset of target RNAs on chromatin and modulating the dynamics of hnRNPA2 homolog nuclear splicing condensates.
Long-read RNA sequencing identifies region- and sex-specific C57BL/6J mouse brain mRNA isoform expression and usage
Authors: Jones Emma F. , Howton Timothy C. , Flanary Victoria L. , Clark Amanda D. , Lasseigne Brittany N. 
Published: January 2024

AbstractAlternative splicing (AS) contributes to the biological heterogeneity between species, sexes, tissues, and cell types. Many diseases are either caused by alterations in AS or by alterations to AS. Therefore, measuring AS accurately and efficiently is critical for assessing molecular phenotypes, including those associated with disease. Long-read sequencing enables more accurate quantification of differentially spliced isoform expression than short-read sequencing approaches, and third-generation platforms facilitate high-throughput experiments. To assess differences in AS across the cerebellum, cortex, hippocampus, and striatum by sex, we generated and analyzed Oxford Nanopore Technologies (ONT) long-read RNA sequencing (lrRNA-Seq) C57BL/6J mouse brain cDNA libraries. From >85 million reads that passed quality control metrics, we calculated differential gene expression (DGE), differential transcript expression (DTE), and differential transcript usage (DTU) across brain regions and by sex. We found significant DGE, DTE, and DTU across brain regions and that the cerebellum had the most differences compared to the other three regions. Additionally, we found region-specific differential splicing between sexes, with the most sex differences in DTU in the cortex and no DTU in the hippocampus. We also report on two distinct patterns of sex DTU we observed, sex-divergent and sex-specific, that could potentially help explain sex differences in the prevalence and prognosis of various neurological and psychiatric disorders in future studies. Finally, we built a Shiny web application for researchers to explore the data further. Our study provides a resource for the community; it underscores the importance of AS in biological heterogeneity and the utility of long-read sequencing to better understand AS in the brain.
Mixed Alkyl/Aryl Phosphonates Identify Metabolic Serine Hydrolases as Antimalarial Targets
Authors: Bennett John M. , Narwal Sunil K. , Kabeche Stephanie , Abegg Daniel , Hackett Fiona , Yeo Tomas , Li Veronica L. , Muir Ryan K. , Faucher Franco F. , Lovell Scott , Blackman Michael J. , Adibekian Alexander , Yeh Ellen , Fidock David A. , Bogyo Matthew 
Published: January 2024

SummaryMalaria, caused byPlasmodium falciparum,remains a significant health burden. A barrier for developing anti-malarial drugs is the ability of the parasite to rapidly generate resistance. We demonstrated that Salinipostin A (SalA), a natural product, kills parasites by inhibiting multiple lipid metabolizing serine hydrolases, a mechanism with a low propensity for resistance. Given the difficulty of employing natural products as therapeutic agents, we synthesized a library of lipidic mixed alkyl/aryl phosphonates as bioisosteres of SalA. Two constitutional isomers exhibited divergent anti-parasitic potencies which enabled identification of therapeutically relevant targets. We also confirm that this compound kills parasites through a mechanism that is distinct from both SalA and the pan-lipase inhibitor, Orlistat. Like SalA, our compound induces only weak resistance, attributable to mutations in a single protein involved in multidrug resistance. These data suggest that mixed alkyl/aryl phosphonates are a promising, synthetically tractable anti-malarials with a low-propensity to induce resistance.
Increased mitochondrial transcription initiation does not promote oxidative phosphorylation
Authors: Miranda Maria , Mesaros Andrea , Kuznetsova Irina , Purrio Martin , Pérard Louise , Filipovska Aleksandra , Mourier Arnaud , Larsson Nils-Göran , Kühl Inge 
Published: January 2024

AbstractPOLRMT is the sole RNA polymerase in human mitochondria where it generates primers for mitochondrial DNA (mtDNA) replication and transcribes the mitochondrial genome to express genes encoding essential components of the oxidative phosphorylation (OXPHOS) system. Elevated POLRMT levels are found in several cancers and in mouse models with severe mitochondrial dysfunction. Here, we generated and characterized mice over-expressingPolrmtto investigate the physiological and molecular consequences of elevated POLRMT levels. Increasing POLRMT did not result in any pathological phenotype but instead positively affected exercise capacity under stress conditions. POLRMT overexpression increasedin organellotranscription initiation, resulting in higher steady-state levels of the promoter-proximal L-strand transcript 7S RNA and higher mtDNA levels. Surprisingly, the abundance of mature mitochondrial RNAs was not affected by the elevated POLRMT levels. Furthermore, ubiquitous simultaneous overexpression of POLRMT and LRPPRC, which stabilizes mitochondrial messenger RNAs, did not increase steady-state levels of mitochondrial transcripts in the mouse. Our data show that POLRMT levels regulate transcription initiation, but additional regulatory steps downstream of transcription initiation and transcript stability limit OXPHOS biogenesis.
Kinases in motion: impact of protein and small molecule interactions on kinase conformations
Authors: Kugler Valentina , Schwaighofer Selina , Feichtner Andreas , Enzler Florian , Fleischmann Jakob , Strich Sophie , Schwarz Sarah , Wilson Rebecca , Tschaikner Philipp , Troppmair Jakob , Sexl Veronika , Meier Pascal , Kaserer Teresa , Stefan Eduard 
Published: January 2024

AbstractProtein kinases act as central molecular switches in the control of cellular functions. Alterations in the regulation and function of protein kinases may provoke diseases including cancer. In this study we investigate the conformational states of such disease-associated kinases using the high sensitivity of the Kinase Conformation (KinCon)-reporter system. We ﬁrst track BRAF-kinase activity conformation changes upon melanoma drug binding. Second, we also use the KinCon reporter technology to examine the impact of regulatory protein interactions on LKB1-kinase tumor suppressor functions. Third, we explore the conformational dynamics of RIP-kinases in response to TNF-pathway activation and small molecule interactions. Finally, we show that CDK4/6 interactions with regulatory proteins alter conformations which remain unaffected in the presence of clinically applied inhibitors. Apart from its predictive value, the KinCon technology helps to identify cellular factors that impact drug efficacies. The understanding of the structural dynamics of full-length protein kinases when interacting with small molecule inhibitors or regulatory proteins is crucial for designing more effective therapeutic strategies.
Transient growth factor expression via mRNA in lipid nanoparticles promotes hepatocyte cell therapy to treat murine liver diseases
Authors: Smith Anna R. , Rizvi Fatima , Everton Elissa , Adeagbo Anisah , Wu Susan , Tam Ying , Muramatsu Hiromi , Pardi Norbert , Weissman Drew , Gouon-Evans Valerie 
Published: January 2024

AbstractPrimary human hepatocyte (PHH) transplantation is a promising alternative to liver transplantation, whereby liver function could be restored by partial repopulation of the diseased organ with healthy cells. However, currently PHH engraftment efficiency is low and benefits are not maintained long-term. Here we refine two mouse models of human chronic and acute liver diseases to recapitulate compromised hepatocyte proliferation observed in nearly all human liver diseases by overexpression of p21 in hepatocytes. In these clinically relevant contexts, we demonstrate that transient, yet robust expression of human hepatocyte growth factor and epidermal growth factor in the liver via nucleoside-modified mRNA in lipid nanoparticles, whose safety was validated with mRNA-based COVID-19 vaccines, drastically improves PHH engraftment, reduces disease burden, and improves overall liver function. This novel strategy may overcome the critical barriers to clinical translation of cell therapies with primary or stem cell-derived hepatocytes for the treatment of liver diseases.
The Porcine Skin Microbiome Exhibits Broad Fungal Antagonism
Authors: Cruz Karinda F. De La , Townsend Elizabeth C. , Cheong JZ Alex , Salamzade Rauf , Liu Aiping , Sandstrom Shelby , Davila Evelin , Huang Lynda , Xu Kayla H. , Wu Sherrie Y. , Meudt Jennifer J. , Shanmuganayagam Dhanansayan , Gibson Angela LF , Kalan Lindsay R 
Published: January 2024

AbstractThe skin and its microbiome function to protect the host from pathogen colonization and environmental stressors. In this study, using the Wisconsin Miniature Swine™ model, we characterize the porcine skin fungal and bacterial microbiomes, identify bacterial isolates displaying antifungal activity, and use whole-genome sequencing to identify biosynthetic gene clusters encoding for secondary metabolites that may be responsible for the antagonistic effects on fungi. Through this comprehensive approach of paired microbiome sequencing with culturomics, we report the discovery of novel species ofCorynebacteriumandRothia. Further, this study represents the first comprehensive evaluation of the porcine skin mycobiome and the evaluation of bacterial-fungal interactions on this surface. Several diverse bacterial isolates exhibit potent antifungal properties against fungal pathogensin vitro. Genomic analysis of inhibitory species revealed a diverse repertoire of uncharacterized biosynthetic gene clusters suggesting a reservoir of novel chemical and biological diversity. Collectively, the porcine skin microbiome represents a potential unique source of novel antifungals.HighlightsPorcine skin bacterial communities are consistent with previous reports on porcine and human skin.Fungal community composition resembles mycobiomes from other mammalian skin, but not human skin.Bacteria isolated from porcine skin have antimicrobial and particularly strong antifungal activityin vitro.Discovered three newCorynebacteriumspecies and one newRothiaspecies.
Investigating the impact of the Internet of Things on higher education: a systematic literature review
Authors: Kandil Omneya , Rosillo Rafael , Abd El Aziz Rasha , De La Fuente David 
Published: January 2024

PurposeThe Internet of things (IoT), an emerging research field, offers solutions to several problems and may result in a paradigm shift in various areas, including education. However, this approach has been under-utilised. Therefore, this research investigates and highlights the primary factors that influence the impact of the IoT on education and reveals the current state of academic research to manage higher education (HE) resources effectively and efficiently.Design/methodology/approachData from 35 academic papers were collected and analysed to understand the current situation and assess the readiness of HE to adopt IoT. A literature review is a well-established method for developing knowledge and interpreting issues under consideration. This study systematically analysed the various research methodologies used to adopt IoT, summarising the content of the studies and highlighting the main factors that may affect IoT adoption in HE.FindingsThe authors examined 95 papers; 35 were investigated and analysed. The literature review and analysis of academic papers revealed the factors influencing the adoption of IoT technology in HE.Originality/valueBy examining the evidence, this study contributes to understanding the context and supplements existing research. It conducts a systematic literature review to assess the impact of the IoT on the educational process, proposes future research directions and presents findings that aid the efficient management of HE resources.