bluuebunny/crossref_metadata_2025 huggingface dataset:
Normal growth curve of choroid plexus in children: Implications for assessing hydrocephalus due to choroid plexus hyperplasia
Authors: Hashimoto Hiroaki , Takemoto Osamu , Nishimoto Keisuke , Moriguchi Gento , Nakamura Motoki , Chiba Yasuyoshi
Published: May 2023

Structured Abstract

Objective

Pediatric hydrocephalus requires evaluation while accounting for growth of intracranial structures, but information on choroid plexus growth in children is lacking. This study aimed to create normal growth curves for intracranial volume, choroid plexus volume, and lateral ventricles volume and assess objectively the degree of hydrocephalus due to choroid plexus hyperplasia (CPH) and the effect of surgeries.

Methods

This retrospective study analyzed head computed tomography (CT) scans of pediatric patients with head trauma from Osaka Women’s and Children’s Hospital between April 2006 and April 2023. The study segmented the intracranial volume, choroid plexus, and lateral ventricles and calculated their volumes. The study also calculated correlation coefficients among the three parameters. Patients aged 0 to 10 years were divided into 15 age-related clusters and mean and standard deviation (SD) values were measured in each cluster. Growth curves were created by plotting mean values sequentially. Volume obtained from patients with CPH were z-normalized using mean and SD values and compared.

Results

A total of 222 CT scans (91 from females) were analyzed, and positive correlations were observed among intracranial volume, choroid plexus volume, and lateral ventricles volume, with the strongest correlation between choroid plexus and lateral ventricles volumes. The growth rate of intracranial volume was rapid until approximately 20 months of ages, while those of choroid plexus and lateral ventricles volume increased rapidly by approximately one year of age.

After that, the volume reached plateau at 1.5 mL and 10mL in choroid plexus and lateral ventricles volume, respectively. Three patients with CPH were enrolled and quantitatively evaluated by the z-normalized volume (z.v.). Notable abnormal volume of choroid plexus (ranged z.v. 26.00 – 45.85) and lateral ventricles (ranged z.v.40.93 – 123.56) were observed. In two patients, z.v. lateral ventricles volumes improved after surgical interventions. Choroid plexus volume reduced by approximately 20% (from z.v. 45.85 to z.v. 36.95) after bilateral endoscopic plexus coagulation in one patient.

Conclusions

This study provides normal growth curves for intracranial volume, choroid plexus volume, and lateral ventricles volume. Knowledge of normal values enables objective assessment of abnormal values related to hydrocephalus and choroid plexus disease such as CPH.
Delineating clinical and developmental outcomes inSTXBP1-related disorders
Authors: Xian Julie , Thalwitzer Kim Marie , McKee Jillian , Sullivan Katie Rose , Brimble Elise , Fitch Eryn , Toib Jonathan , Kaufman Michael C. , deCampo Danielle , Cunningham Kristin , Pierce Samuel R. , Goss James , Son Rigby Charlene , Syrbe Steffen , Boland Michael , Prosser Ben , Fitter Nasha , Ruggiero Sarah M. , Helbig Ingo
Published: May 2023

STXBP1-related disorders are among the most common genetic epilepsies and neurodevelopmental disorders. However, the longitudinal epilepsy course and developmental endpoints have not yet been described in detail, which is a critical prerequisite for clinical trial readiness. Here, we assessed 1,281 cumulative patient-years of seizure and developmental histories in 162 individuals withSTXBP1-related disorders and established a natural history framework.STXBP1-related disorders are characterized by a dynamic pattern of seizures in the first year of life and high variability in neurodevelopmental trajectories in early childhood. Epilepsy onset differed across seizure types, with 90% cumulative onset for infantile spasms by 6 months and focal-onset seizures by 27 months of life. Epilepsy histories diverged between variant subgroups in the first 2 years of life, when individuals with protein-truncating variants and deletions inSTXBP1(n=39) were more likely to have infantile spasms between 5 and 6 months followed by seizure remission, while individuals with missense variants (n=30) had an increased risk for focal seizures and ongoing seizures after the first year. Developmental outcomes were mapped using milestone acquisition data in addition to standardized assessments including the Gross Motor Function Measure-66 Item Set and the Grasping and Visual-Motor Integration subsets of the Peabody Developmental Motor Scales. Quantification of endpoints revealed high variability during the first five years of life, with emerging stratification between clinical subgroups, most prominently between individuals with and without infantile spasms. We found that individuals with neonatal seizures or early infantile seizures followed by seizure offset by 12 months of life had more predictable seizure trajectories in early to late childhood than compared to individuals with more severe seizure presentations, including individuals with refractory epilepsy throughout the first year. Characterization of anti-seizure medication response revealed age-dependent response over time, with phenobarbital, levetiracetam, topiramate, and adrenocorticotropic hormone effective in reducing seizures in the first year of life, while clobazam and the ketogenic diet were effective in long-term seizure management. Virtual clinical trials using seizure frequency as the primary outcome resulted in wide range of trial success probabilities across the age span, with the highest probability in early childhood between 1 year and 3.5 years. In summary, we delineated epilepsy and developmental trajectories inSTXBP1-related disorders using standardized measures, providing a foundation to interpret future therapeutic strategies and inform rational trial design.
Has the COVID-19 Pandemic Changed Parental Attitudes and Beliefs Regarding Vaccinating their Children against the Flu?
Authors: Shmueli Liora
Published: May 2023

Introduction

This study assessed whether the COVID-19 pandemic has altered parents’ attitudes toward vaccinating their children against the flu, and the contributing socio-demographic, health-related, and behavioral factors, as well as barriers to school-based vaccination programs.

Methods

We conducted a cross-sectional online survey of parents of children aged 6 months to 11 years in Israel (n=975) between December 21–31, 2022. A multivariate regression was performed to determine predictors of these parents’ willingness to vaccinate their children aged 6 months to 11 years against the flu in the winter of 2023 (December 2022–February 2023).

Results

Overall, 45% of parents stated that they did not intend to vaccinate their children against the flu in the winter of 2023, citing fears of side effects and concerns about vaccine effectiveness. Among those who did not trust the Ministry of Health and pharmaceutical companies prior to the pandemic, this trend increased in 78% of them following the COVID-19 events. In contrast, 39% of parents stated that they had already vaccinated their children against the flu, with an additional 16% intending to do so. Forty-one percent reported an increased intention following the pandemic. Only 37% of parents vaccinated their children at school in grades 2–4, mainly due to a preference for HMO clinics and lack of available nurses at school. The Health Belief Model (HBM) variables, namely, perceived susceptibility, severity and benefits, displayed the largest effect sizes.

Conclusions

Understanding the impact of the COVID-19 pandemic on parents’ willingness to vaccinate their children against the flu is crucial. Notably, the pandemic has increased vaccine receptivity among some parents. Healthcare providers and public health officials need to address parents’ concerns about the safety and efficacy of the influenza vaccine to improve vaccination rates among children. Implementing school-based vaccination programs is an important strategy for promoting public health, but may be challenging. To increase uptake, nursing staff in student health facilities should be more accessible, and clear explanations about the efficacy of nasal spray vaccinations should be provided.
Molecular surveillance detects high prevalence of the neglected parasiteMansonella ozzardiin the Colombian Amazon
Authors: Dahmer KJ , Palma-Cuero M , Ciuoderis K , Patiño C , Roitman S , Li Z , Sinha A , Hite JL , Bellido Cuellar O , Hernandez-Ortiz JP , Osorio JE , Christensen BM , Carlow CKS , Zamanian M
Published: May 2023

Mansonellosis is an undermapped insect-transmitted disease caused by filarial nematodes that are estimated to infect hundreds of millions of people globally. Despite their prevalence, there are many outstanding questions regarding the general biology and health impacts of the responsible parasites. Historical reports suggest that the Colombian Amazon is endemic for mansonellosis and may serve as an ideal location to pursue these questions in the backdrop of other endemic and emerging pathogens. We deployed molecular and classical diagnostic approaches to surveyMansonellaprevalence among adults belonging to indigenous communities along the Amazon River and its tributaries near Leticia, Colombia. Deployment of a loop-mediated isothermal amplification (LAMP) assay on blood samples revealed an infection prevalence of ∼40% forMansonella ozzardi. This assay identified significantly more infections than blood smear microscopy or LAMP assays performed using plasma, likely reflecting greater sensitivity and the ability to detect low microfilaremias or occult infections.Mansonellainfection rates increased with age and were higher among males compared to females. Genomic analysis confirmed the presence ofM. ozzardithat clusters closely with strains sequenced in neighboring countries. We successfully cryopreserved and revitalizedM. ozzardimicrofilariae, advancing the prospects of rearing infective larvae in controlled settings. These data suggest an underestimation of true mansonellosis prevalence, and we expect that these methods will help facilitate the study of mansonellosis in endemic and laboratory settings.
Extracellular diadenosine tetraphosphate (Ap4A) is recognized by the plasma membrane purinoreceptor P2K1/DORN1 and closes stomata inArabidopsis thaliana
Authors: Dobrogojski Jędrzej , Nguyen Van Hai , Kowalska Joanna , Borek Sławomir , Pietrowska-Borek Małgorzata
Published: May 2023

Dinucleoside polyphosphates (NpnNs) are considered novel signalling molecules involved in the induction of plant defence mechanisms. However, the NpnNs signal recognition and transduction are still enigmatic. Here we report, for the first time, that diadenosine tetraphosphate (Ap4A) is recognized by theArabidopsis thalianapurinoreceptor P2K1/DORN1 (Does Not Respond to Nucleotides 1) and causes stomatal closure.

Extracellular Ap4A- and dicytidine tetraphosphate (Cp4C)-induced stomatal closure was observed using a microscope. Reactive oxygen species (ROS) accumulation was determined by staining with nitroblue tetrazolium (NBT) and 3,3ʹ-diaminobenzidine tetrahydrochloride (DAB). Transcriptional changes were determined by quantitative real-time PCR. Wild-type Col-0 and thedorn1-3 A. thalianaknockout mutant were used.

Examination of the leaf epidermisdorn1-3mutant provided evidence that P2K1/DORN1 recognizes extracellular Ap4A but not Cp4C. ROS are involved in signal transduction caused by Ap4A and Cp4C, leading to stomatal closure. Ap4A induced and Cp4C suppressed the transcriptional response in wild-type plants. Moreover, indorn1-3leaves, the effect of Ap4A on gene expression was impaired.

Our research demonstrated, for the first time, that P2K1/DORN1 is a plant purinoreceptor for Ap4A. This interaction leads to changes in the transcription of signalling hubs in signal transduction pathways.
Protein intrinsically disordered regions have a non-random, modular architecture
Authors: McConnell Brendan S. , Parker Matthew W.
Published: May 2023

Motivation

Protein sequences can be broadly categorized into two classes: those which adopt stable secondary structure and fold into a domain (i.e., globular proteins), and those that do not. The sequences belonging to this latter class are conformationally heterogeneous and are described as being intrinsically disordered. Decades of investigation into the structure and function of globular proteins has resulted in a suite of computational tools that enable their sub-classification by domain type, an approach that has revolutionized how we understand and predict protein functionality. Conversely, it is unknown if sequences of disordered protein regions are subject to broadly generalizable organizational principles that would enable their sub-classification.

Results

Here we report the development of a statistical approach that quantifies linear variance in amino acid composition across a sequence. With multiple examples we provide evidence that intrinsically disordered regions are organized into statistically non-random modules of unique compositional bias. Modularity is observed for both low and high complexity sequences and, in some cases, we find that modules are organized in repetitive patterns. These data demonstrate that disordered sequences are non-randomly organized into modular architectures and motivate future experiments to comprehensively classify module types and to determine the degree to which modules constitute functionally separable units analogous to the domains of globular proteins.

Availability and implementation

The source code, documentation, and data to reproduce all figures is freely available athttps://github.com/MWPlabUTSW/Chi-Score-Analysis.git. The analysis is also available as a Google Colab Notebook (https://colab.research.google.com/github/MWPlabUTSW/Chi-Score-Analysis/blob/main/ChiScore_Analysis.ipynb).
SETDB1 Triple Tudor Domain Ligand, (R,R)-59, Promotes Methylation of Akt1 in Cells
Authors: Uguen Mélanie , Deng Yu , Li Fengling , Shell Devan J. , Norris-Drouin Jacqueline L. , Stashko Michael A. , Ackloo Suzanne , Arrowsmith Cheryl H. , James Lindsey I. , Liu Pengda , Pearce Kenneth H. , Frye Stephen V.
Published: May 2023

Increased expression and hyperactivation of the methyltransferase SETDB1 are commonly observed in cancer and central nervous system disorders. However, there are currently no reported SETDB1-specific methyltransferase inhibitors in the literature, suggesting this is a challenging target. Here, we disclose that the previously reported small-molecule ligand for SETDB1’s Triple Tudor Domain, (R,R)-59, is unexpectedly able to increase SETDB1 methyltransferase activity bothin vitroand in cells. Specifically, (R,R)-59 promotesin vitroSETDB1-mediated methylation of lysine 64 of the protein kinase Akt1. Treatment with (R,R)-59 also increased Akt1 threonine 308 phosphorylation and activation, a known consequence of Akt1 methylation, resulting in stimulated cell proliferation in a dose-dependent manner. (R,R)-59 is the first SETDB1 small-molecule positive activator for the methyltransferase activity of this protein. Mechanism of action studies show that full-length SETDB1 is required for significantin vitromethylation of an Akt1-K64 peptide, and that this activity is stimulated by (R,R)-59 primarily through an increase in catalytic activity rather than a change in SAM binding.

Abstract Figure
Molecular motor tug-of-war regulates elongasome cell wall synthesis dynamics inBacillus subtilis
Authors: Middlemiss Stuart , Blandenet Matthieu , Roberts David M , McMahon Andrew , Grimshaw James , Edwards Joshua M , Sun Zikai , Whitley Kevin D , Blu Thierry , Strahl Henrik , Holden Séamus
Published: May 2023

Most rod-shaped bacteria elongate by inserting new cell wall material into the inner surface of the cell sidewall. This is performed by class A penicillin binding proteins (PBPs) and a highly conserved protein complex, the elongasome, which moves processively around the cell circumference and inserts long glycan strands that act as barrel-hoop-like reinforcing structures, thereby giving rise to a rod-shaped cell. However, it remains unclear how elongasome synthesis dynamics and termination events are regulated to determine the length of these critical cell-reinforcing structures. To address this, we developed a method to track individual elongasome complexes around the entire circumference ofBacillus subtiliscells for minutes-long periods using single molecule fluorescence microscopy. We found that theB. subtiliselongasome is highly processive and that processive synthesis events are frequently terminated by rapid reversal or extended pauses. We found that cellular levels of RodA regulate elongasome processivity, reversal and pausing. Our single molecule data, together with stochastic simulations, show that elongasome dynamics and processivity are regulated by molecular motor tug-of-war competition between several, likely two, oppositely oriented peptidoglycan synthesis complexes associated with the MreB filament. Our data, thus, demonstrate that molecular motor tug-of-war is a key regulator of elongasome dynamics inB. subtilis, which likely also regulates the cell shape via modulation of elongasome processivity.
Phosphorylated trimeric SOSS1 complex and RNA polymerase II trigger liquid-liquid phase separation at double-strand breaks
Authors: Long Qilin , Sebesta Marek , Sedova Katerina , Haluza Vojtech , Alagia Adele , Liu Zhichao , Stefl Richard , Gullerova Monika
Published: May 2023

The most toxic forms of DNA damage are double-strand breaks (DSBs). We have previously shown that RNA polymerase II (RNAPII), phosphorylated at tyrosine 1 (Y1P) on the C- terminal domain, transcribes RNA at DSBs to promote efficient DNA repair. However, it is still unknown how transcription is regulated at DSBs. Here, we show that the trimeric SOSS1 complex (hSSB1, INTS3, and c9orf80) binds to Y1P RNAPII in response to DNA damage, hSSB1 binds to R-loops, and formation of the SOSS1 complex is required for the coexistence of replication protein A (RPA) and hSSB1 at DSBs. The damage-activated tyrosine kinase c- Abl phosphorylates hSSB1 to enable its binding to Y1P RNAPII and its recruitment to DSBs. Finally, we show bothin vitroandin vivothat the SOSS1 complex and RNAPII form dynamic repair compartments at DSBs via liquid-liquid phase separation (LLPS). The loss of the trimeric SOSS1 leads to impaired DNA repair, highlighting its biological importance in the RNA-dependent DNA damage response.

Teaser

Trimeric SOSS1 complex and transcription contribute to phase separation at double-strand DNA breaks.
Extensive T1-weighted MRI Preprocessing Improves Generalizability of Deep Brain Age Prediction Models⋆
Authors: Dular Lara , Pernuš Franjo , Špiclin Žiga
Published: May 2023

Brain age is an estimate of chronological age obtained from T1-weighted magnetic resonance images (T1w MRI) and represents a simple diagnostic biomarker of brain ageing and associated diseases. While the current best accuracy of brain age predictions on T1w MRIs of healthy subjects ranges from two to three years, comparing results from different studies is challenging due to differences in the datasets, T1w preprocessing pipelines, and performance metrics used. This paper investigates the impact of T1w image preprocessing on the performance of four deep learning brain age models presented in recent literature. Four preprocessing pipelines were evaluated, differing in terms of registration, grayscale correction, and software implementation. The results showed that the choice of software or preprocessing steps can significantly affect the prediction error, with a maximum increase of 0.7 years in mean absolute error (MAE) for the same model and dataset. While grayscale correction had no significant impact on MAE, the affine registration, compared to the rigid registration of T1w images to brain atlas was shown to statistically significantly improve MAE. Models trained on 3D images with isotropic 1mm3resolution exhibited less sensitivity to the T1w preprocessing variations compared to 2D models or those trained on downsampled 3D images. Some proved invariant to the preprocessing pipeline, however only after offset correction. Our findings generally indicate that extensive T1w preprocessing enhances the MAE, especially when applied to a new dataset. This runs counter to prevailing research literature which suggests that models trained on minimally preprocessed T1w scans are better poised for age predictions on MRIs from unseen scanners. Regardless of model or T1w preprocessing used, we show that to enable generalization of model’s performance on a new dataset with either the same or different T1w preprocessing than the one applied in model training, some form of offset correction should be applied.

Highlights

Intensive preprocessing improves performance of computationally less demanding models.

Models trained on 1mm3MRIs are most insensitive to the choice of preprocessing.

Change in preprocessing increased MAE up to 0.7 years for the same model and dataset.

Preprocessing software used may impact model performance.

Prediction bias is systematic across the whole age span and inherent to each model.
Isolation of a Chlamydia Strain from Lung Tissue Samples in Healthy Chickens Exhibiting Antagonistic Effects on Avian Infectious Bronchitis Virus
Authors: Zhen Miaoxiao
Published: May 2023

To assess the feasibility of isolating Chlamydia strains with antiviral activity against avian infectious bronchitis virus (IBV) from healthy chickens in farms, 58 Chlamydia strains were obtained from 160 lung tissue samples collected across ten chicken farms, yielding an overall isolation rate of 36.25%. SPF chickens co-infected with Chlamydia and IBV were employed for verification, leading to the identification of eight strains (Bi≥ 0.800) with potent antiviral effects against IBV, accounting for 13.79% of the total isolated strains. The top-performing strain, Y17 Chlamydia strain, was selected and subjected to cell co-culture and U-tube experiments with IBV. Results demonstrated that the Y17 Chlamydia strain significantly impeded IBV replication in chicken tracheal epithelial cells (P<0.01) and did not secrete or induce host cells to secrete extracellular metabolites with antagonistic effects on IBV infection in U-tube experiments (P>0.05), suggesting that its antiviral activity was cell-autonomous. Our research highlights the feasibility of isolating Chlamydia strains with antiviral activity against IBV from healthy chickens and suggests that antiviral strains could be widespread, even though their efficacy against viruses is strain-specific. The presence of broad-spectrum antiviral Chlamydia strains may also be possible. Considering the prevalence of Chlamydia strains in vertebrate hosts, along with the fact that some strains are either non-pathogenic or display low toxicity, our findings could offer a fresh perspective on the prevention and treatment of viral infections in vertebrates.
Diversity and Evolution of an Abundant ICEclc-Family of Integrative and Conjugative Elements inPseudomonas aeruginosa
Authors: Benigno Valentina , Carraro Nicolas , Sarton-Lohéac Garance , Romano-Bertrand Sara , Blanc Dominique S. , van der Meer Jan Roelof
Published: May 2023

Integrative and conjugative elements (ICEs) are widespread autonomous mobile DNA, containing the genes necessary for their excision, conjugative transfer, and insertion into a new host cell. ICEs can carry additional genes that are non-essential for their transfer, but that can confer adaptive phenotypes to the host. Our aim here was to better characterize the presence, distribution and evolution of ICEs related to the well-described ICEclcamongPseudomonas aeruginosaclinical isolates, and to understand their potential role in spreading genes with adaptive benefit. We examined a total of 181P. aeruginosagenome sequences obtained from patient or hospital environment isolates. More than 90% of the isolates carried one or more ICEclc-like elements, with different degrees of conservation to the known ICEclc-lifestyle and transfer genes. ICE clones closely matched their host clonal phylogeny, but not exclusively, indicating that both clonal evolution and ICE-horizontal transfer are occurring in the hospital environment. Variable gene regions among the clinicalP. aeruginosaICEclc-type elements were notably enriched for heavy metal resistance genes, toxin-antitoxin systems, potential efflux systems and multidrug resistance proteins, a metalloprotease and for a variety of regulatory systems, but not for specific recognizable antibiotic resistance cassettes. Clonal persistence suggests adaptive benefits of these functional categories; and micro-patterns of gene gain and loss indicate ongoing ICE evolution within theP. aeruginosahosts.
Evaluation of ready-to-use freezer stocks of a synthetic microbial community for maize root colonization
Authors: Parnell J. Jacob , Vintila Simina , Tang Clara , Wagner Maggie R. , Kleiner Manuel
Published: May 2023

Synthetic microbial communities (SynComs) are a valuable tool to study community assembly patterns, host-microbe interactions, and microbe-microbe interactions in a fully controllable setting. Constructing the SynCom inocula for plant-microbe experiments can be time consuming and difficult because a large number of isolates with different media requirements and growth rates are grown in parallel and mixed to appropriate titers. A potential workaround to assembling fresh SynCom inocula for every experiment could be to pre-make and freeze SynComs on a large scale, creating ready-to-use stock inocula. The objective of this study was to compare the reproducibility, stability, and colonization ability of freshly prepared versus frozen SynCom inocula. We used a community of seven species known to colonize maize roots. The results from inoculation with the frozen SynCom were as consistent as standardizedde novoconstruction of fresh SynCom. Our results indicate that creating frozen SynCom inocula for repeated use in experiments not only saves time, but could also improve cross-experiment reproducibility. Although this approach was only validated with one SynCom, it demonstrates a principle that can be tested for improving approaches in constructing other SynComs.

Importance

Synthetic communities (SynComs) are an invaluable tool to characterize and model plant-microbe interactions. Multimember SynComs approximate intricate real-world interactions between plants and their microbiome, but the complexity and time required for their construction increases enormously for each additional member added to the SynCom. Therefore, researchers who study a diversity of microbiomes using SynComs are looking for ways to simplify the use of SynComs. In this manuscript, we evaluate the feasibility of creating ready-to-use freezer stocks of a well-studied seven-member SynCom for maize roots. The frozen ready-to-use SynCom stocks work according to the principle of “just add buffer and apply to sterilized seeds or seedlings” and thus can save multiple days of laborious growing and combining of multiple microorganisms. We show that ready-to-use SynCom stocks provide comparable results to freshly constructued SynComs and thus allow for large time savings when working with SynComs.
Machine learning uncovers thePseudomonas syringaetranscriptome in microbial communities and during infection
Authors: Bajpe Heera , Rychel Kevin , Lamoureux Cameron R. , Sastry Anand V. , Palsson Bernhard O.
Published: May 2023

The transcriptional regulatory network (TRN) of the phytopathogenPseudomonas syringaepv.tomatoDC3000 regulates its response to environmental stimuli, including interactions with hosts and neighboring bacteria. Despite the importance of transcriptional regulation during these agriculturally-significant interactions, a comprehensive understanding of the TRN ofP. syringaeis yet to be achieved. Here, we collected and decomposed a compendium of public RNA-seq data fromP. syringaeto obtain 45 independently modulated gene sets (iModulons) that quantitatively describe the TRN and its activity state across diverse conditions. Through iModulon analysis, we 1) untangle the complex interspecies interactions betweenP. syringaeand other terrestrial bacteria in cocultures, 2) expand the current understanding of theArabidopsis thaliana-P. syringaeinteraction, and 3) elucidate the AlgU-dependent regulation of flagellar gene expression. The modularized TRN yields a unique understanding of interaction-specific transcriptional regulation inP. syringae.

Importance

Pseudomonas syringaepv.tomatoDC3000 is a model plant pathogen that infects tomatoes andArabidopsis thaliana. The current understanding of global transcriptional regulation in the pathogen is limited. Here, we applied iModulon analysis to a compendium of RNA-seq data to unravel its transcriptional regulatory network. We characterize each co-regulated gene set, revealing the activity of major regulators across diverse conditions. We provide new insights on the transcriptional dynamics in interactions with the plant immune system and with other bacterial species, such as AlgU-dependent regulation of flagellar genes during plant infection and downregulation of siderophore production in the presence of a siderophore cheater. This study demonstrates the novel application of iModulons in studying temporal dynamics during host-pathogen and microbe-microbe interactions, and reveals specific insights of interest.
In vitromethylation of the U7 snRNP subunits Lsm11 and SmE by the PRMT5/MEP50/pICln methylosome
Authors: Yang Xiao-cui , Desotell Anthony , Lin Min-Han , Paige Andrew S. , Malinowska Agata , Sun Yadong , Aik Wei Shen , Dadlez Michał , Tong Liang , Dominski Zbigniew
Published: May 2023

U7 snRNP is a multi-subunit endonuclease required for 3’ end processing of metazoan replication-dependent histone pre-mRNAs. In contrast to the spliceosomal snRNPs, U7 snRNP lacks the Sm subunits D1 and D2 and instead contains two related proteins, Lsm10 and Lsm11. The remaining five subunits of the U7 heptameric Sm ring, SmE, F, G, B and D3, are shared with the spliceosomal snRNPs. The pathway that assembles the unique ring of U7 snRNP is unknown. Here, we show that a heterodimer of Lsm10 and Lsm11 tightly interacts with the methylosome, a complex of the arginine methyltransferase PRMT5, MEP50 and pICln known to methylate arginines in the C-terminal regions of the Sm proteins B, D1 and D3 during the spliceosomal Sm ring assembly. Both biochemical and Cryo-EM structural studies demonstrate that the interaction is mediated by PRMT5, which binds and methylates two arginine residues in the N-terminal region of Lsm11. Surprisingly, PRMT5 also methylates an N-terminal arginine in SmE, a subunit that does not undergo this type of modification during the biogenesis of the spliceosomal snRNPs. An intriguing possibility is that the unique methylation pattern of Lsm11 and SmE plays a vital role in the assembly of the U7 snRNP.
Lactobacillusmaintains IFNγ homeostasis to promote behavioral stress resilience
Authors: Merchak Andrea R. , Wachamo Samuel , Brown Lucille C. , Thakur Alisha , Moreau Brett , Brown Ryan M. , Rivet-Noor Courtney , Raghavan Tula , Gaultier Alban
Published: May 2023

The gut microbiome consists of the trillions of bacteria, fungi, and viruses that inhabit the digestive tract. These communities are sensitive to disruption from environmental exposures ranging from diet changes to illness. Disruption of the community of lactic acid producing bacteria,Lactobaccillacea, has been well documented in mood disorders and stress exposure. In fact, oral supplement with manyLactobacillusspecies can ameliorate these effects, preventing depression- and anxiety-like behavior. Here, for the first time, we utilize a gnotobiotic mouse colonized with the Altered Schaedler Flora to remove the two native species ofLactobaccillacea. Using this novel microbial community, we found that theLactobacillusspecies themselves, and not the disrupted microbial communities are protective from environmental stressors. Further, we determine thatLactobaccillaceaare maintaining homeostatic IFNγ levels which are mediating these behavioral and circuit level responses. By utilizing the Altered Schaedler Flora, we have gained new insight into how probiotics influence behavior and give novel methods to study potential therapies developed to treat mood disorders.
Behavioral Classification of Sequential Neural Activity Using Time Varying Recurrent Neural Networks
Authors: Zhang Yongxu , Mitelut Catalin , Arpin David J. , Vaillancourt David , Murphy Timothy , Saxena Shreya
Published: May 2023

Shifts in data distribution across time can strongly affect early classification of time-series data. When decoding behavior from neural activity, early detection of behavior may help in devising corrective neural stimulation before the onset of behavior. Recurrent Neural Networks (RNNs) are common models for sequence data. However, standard RNNs are not able to handle data with temporal distributional shifts to guarantee robust classification across time. To enable the network to utilize all temporal features of the neural input data, and to enhance the memory of an RNN, we propose a novel approach: RNNs with time-varying weights, here termed Time-Varying RNNs (TV-RNNs). These models are able to not only predict the class of the time-sequence correctly but also lead to accurate classification earlier in the sequence than standard RNNs. In this work, we focus on early sequential classification of brain-wide neural activity across time using TV-RNNs applied to a variety of neural data from mice and humans, as subjects perform motor tasks. Finally, we explore the contribution of different brain regions on behavior classification using SHapley Additive exPlanation (SHAP) value, and find that the somatosensory and premotor regions play a large role in behavioral classification.
Mammalian orthoreovirus infection in human epidermal growth factor receptor 2 positive (HER2+) breast cancer cells
Authors: Jandick Nicole A. , Kirner Nicolette , Miller Cathy L.
Published: May 2023

Mammalian orthoreovirus (MRV) is a clinically benign oncolytic virus which has been investigated for use in multiple cancer types, including breast cancer (BC). In human clinical trials, MRV has been shown to be safe, and multiple BC patients have shown partial responses to intratumoral and intravenous virus delivery. Combination therapies inclusive of MRV and current FDA approved BC chemotherapies are being investigated to target metastatic, early BC, and triple negative BC. Though MRV is being tested clinically, we still do not fully understand the highly variable patient responses to MRV therapy. One of the most aggressive BC subtypes is HER2+ BC, in which human epidermal growth factor receptor 2 (HER2) is dysregulated, resulting in increased growth, survival, and metastasis of cancer cells. FDA approved therapies, trastuzumab and pertuzumab, target HER2 to prevent signaling of the phosphoinositide 3-kinase (PI3K) pathway. However, recent findings show that accumulation of hypoxia inducible factor-1 alpha (HIF-1α) in HER2+ BC cells contributes to trastuzumab resistance. In this work, we provide evidence that MRV infects, replicates in, and kills HER2 overexpressing cells. MRV infection is also found to have variable effects on signaling pathways that activate or are activated by HER2 expression. Finally, we show that MRV reduces HIF-1α accumulation in all the cell lines tested, including a HER2+ BC cell line. These studies provide further evidence that MRV holds promise for use in conjunction with trastuzumab to treat HER2+ BC patients.
Mpox diagnosis history, behavioural risk modification, and vaccination uptake in gay, bisexual, and other men who have sex with men in the UK: findings from a large, online community cross-sectional survey (RiiSH-Mpox) undertaken November/December 2022
Authors: Ogaz Dana , Enayat Qudsia , Brown Jack RG , Phillips Dawn , Wilkie Ruth , Jayes Danielle , Reid David , Hughes Gwenda , Mercer Catherine H , Saunders John , Mohammed Hamish
Published: May 2023

Mpox cases, first identified as part of the multi-country outbreak in May 2022, rapidly fell in the UK from September 2022. Public health responses included community-coordinated messaging and a targeted mpox vaccination in eligible gay, bisexual, and other men who have sex with men (GBMSM). Using data from an online, community survey of GBMSM (November/December 2022), we examined self-reported mpox diagnoses, behavioural risk modification, and mpox vaccination offer and uptake (≥1 dose). Thirty-five participants (2.6%, 35/1,333) were ever mpox test positive; half (53%, 707/1,333) reported behaviour modification to avoid mpox. In GBMSM considered vaccine eligible, uptake was 69% (95% CI: 65%-72%, 601/875) or 92% (95% CI: 89%-94%, 601/655) in those eligible and offered. GBMSM self-identifying as bisexual, those with lower educational qualifications, and those unemployed were less likely to be vaccinated. Equitable mpox vaccine offer and provision is needed to minimise the risk of future outbreaks and mpox-related health inequalities.
Diagnosis coding of Chronic Kidney Disease in Type 2 Diabetes in UK primary care
Authors: Sisk Rose , Cameron Rory , Tahir Waqas , Sammut-Powell Camilla
Published: May 2023

1.

Background

Type 2 diabetes (T2D) is a leading cause of both chronic kidney disease (CKD) and onward progression to end stage renal disease. Timely diagnosis coding of CKD in patients with T2D could lead to improvements in quality of care and patient outcomes.

Aim

To assess the consistency between estimated glomerular filtration rate (eGFR) based evidence of CKD and CKD diagnosis coding in UK primary care.

Design and Setting

A retrospective analysis of electronic health record data in a cohort of people with type 2 diabetes from 60 primary care centres within England between 2012 and 2022.

Method

We estimated the incidence rate of CKD per 100 person-years using eGFR-based CKD and diagnosis codes. Logistic regression was applied to establish which attributes were associated with diagnosis coding. Time from eGFR-based CKD to entry of a diagnosis code was summarised using the median and interquartile range.

Results

The overall incidence of CKD was 2.32 (95% CI: 2.24, 2.41) and significantly different between eGFR-based criteria and diagnosis codes: 1.98 (95% CI: 1.90, 2.05) vs 1.06 (95% CI: 1.00, 1.11) respectively; p<0.001. Only 46% of CKD incidences identified using eGFR-based criteria had a corresponding diagnosis code. Younger patients, patients with a higher severity CKD stage, and patients with an observed urine-albumin-to-creatinine ratio were more likely to have a diagnosis code.

Conclusion

Diagnosis coding of patients with eGFR-based evidence of CKD in UK primary care is poor within patients with type 2 diabetes, despite CKD being a well-known complication of diabetes.

2.

How this fits in

Type 2 diabetes is a recognised cause of chronic kidney disease (CKD), and early identification and management of CKD can reduce the risk of progression and related complications. Diagnosis coding of CKD is associated with better patient outcomes, yet we have observed that less than half of patients with type 2 diabetes who meet eGFR-based criteria for stage 3-5 CKD have a CKD diagnosis code in their primary care record. There is a need to understand why CKD diagnosis coding practices are subpar in primary care and this research acts as a call-to-action to improve.
Phase relations of interneuronal activity relative to theta rhythm
Authors: Mysin Ivan
Published: May 2023

The theta rhythm plays a crucial role in synchronizing neural activity during attention and memory processes. However, the mechanisms behind the formation of neural activity during theta rhythm generation remain unknown. To address this, we propose a mathematical model that explains the distribution of interneurons in the CA1 field during the theta rhythm phase. Our model consists of a network of seven types of interneurons in the CA1 field that receive inputs from the CA3 field, entorhinal cortex, and local pyramidal neurons in the CA1 field. By adjusting the parameters of the connections in the model. We demonstrate that it is possible to replicate the experimentally observed phase relations between interneurons and the theta rhythm. Our model predicts that populations of interneurons receive unimodal excitation and inhibition with coinciding peaks, and that excitation dominates to determine the firing dynamics of interneurons.
Efficient and accurate KIR and HLA genotyping with massively parallel sequencing data
Authors: Song Li , Bai Gali , Liu X. Shirley , Li Bo , Li Heng
Published: May 2023

Killer cell immunoglobulin like receptor (KIR) genes and human leukocyte antigen (HLA) genes play important roles in innate and adaptive immunity. They are highly polymorphic and cannot be genotyped with standard variant calling pipelines. Compared with HLA genes, many KIR genes are similar to each other in sequences and may be absent in the chromosomes. Therefore, although many tools have been developed to genotype HLA genes using common sequencing data, none of them work for KIR genes. Even specialized KIR genotypers could not resolve all the KIR genes. Here we describe T1K, a novel computational method for the efficient and accurate inference of KIR or HLA alleles from RNA-seq, whole-genome sequencing, or whole-exome sequencing data. T1K jointly considers alleles across all genotyped genes, so it can reliably identify present genes and distinguish homologous genes, including the challengingKIR2DL5A/KIR2DL5Bgenes. This model also benefits HLA genotyping, where T1K achieves high accuracy in benchmarks. Moreover, T1K can call novel single-nucleotide variants and process single-cell data. Applying T1K to tumor single-cell RNA-seq data, we found thatKIR2DL4expression was enriched in tumor-specific CD8+T cells. T1K may open the opportunity for HLA and KIR genotyping across various sequencing applications.
Consumer decisions toward halal purchase before and during COVID-19 pandemic: a grey relational analysis approach
Authors: Lee Tzong-Ru , Lin Yong-Shun , Kassim Erne Suzila , Sebastian Stephanie
Published: May 2023

Purpose

The main objective of this research is to investigate the factors that influence consumer purchase decisions for halal products before and during the COVID-19 pandemic, based on the Engel-Kollat-Blackwell (EKB) theory.

Design/methodology/approach

The research was conducted as a survey. The influencing factors were determined based on the grey relational analysis (GRA) approach.

Findings

The findings indicate before the COVID-19 pandemic, consumers mainly purchased halal products based on four key factors: purchasing experience, certification label, Internet searches and past consumption experience. However, during the pandemic, the ranking and factors have changed to six indicators, which are past consumption experience, purchasing experience, certification labels, standardized specifications, Internet searches and halal certification labels.

Research limitations/implications

The study was limited by the sample size and geographical area. Nevertheless, the findings could be further explored by expanding related theories toward understand human decisions based on spiritual beliefs.

Practical implications

The findings of this study have important implications for research, practice and society. Understanding the factors influencing halal purchase decisions before and during the pandemic can help businesses, policymakers and halal certification bodies to better cater to consumers' needs and preferences and ensure the continued growth and development of the halal industry.

Originality/value

This study evaluates halal purchasing decisions between periods of certainty and uncertainty by using the GRA. Changes in halal consumption and purchase decisions in response to COVID-19 pandemic have become an emerging topic of discovery. The study addresses the gap in the literature regarding changes in consumer decision pattern.
Pabiben.com – integrating Gandhian philosophies for business growth
Authors: Nagori Viral
Published: May 2023

Learning outcomes

The learning outcomes are as follows: to strike a balance between business growth and keeping the core Gandhian philosophies intact; to evaluate the relevance of Gandhian philosophy in the age of the digital era, especially for the grassroots enterprises; and to identify the leadership characteristics demonstrated by Pabiben from the lens of servant-leadership theory.

Case overview/synopsis

The case describes the journey of a grassroots-based rural women entrepreneur, Pabibben, who had created an artisan's enterprise and rural business model based on Gandhian philosophies. The case focuses on whether Gandhian philosophies are still relevant in today's time for business growth. The case appeals to the academic fraternity, budding entrepreneurs, social sector start-ups and practitioners who believe in the inclusive and holistic growth of an individual, community, society and the nation.

The case is about the dilemma of how to grow a business ethically and balance economic and social gain. Pabiben used Gandhian philosophies as a set of values to make decisions and set policies for her business. Pabiben wanted to grow her business and expand her e-commerce portal “Pabiben.com” for other artisans to display, promote and sell their products to the global communities. She had to decide on the following:

1. Should she sell other artisans' products under “Pabiben.com”?

2. Should she allow other artisans to create their own identity on the portal and help the artisans' community grow?

3. Are Gandhian philosophies still relevant in today’s time for business growth?
Innovation as a catalyst for Moonj artisans: a case of Rekhaakriti
Authors: Kumar Shubham , Mathur Tanuj , Misra Himanshu
Published: May 2023

Learning outcomes

The readers will gain practical insights on the key attributes of a women entrepreneur, the role of innovative product design and usage, the core challenges and opportunities and the strategies to overcome entrepreneurial hurdles in the Moonj handicraft business.

Case overview/synopsis

The case is about “Rekhaakriti”, a handicraft artisan-oriented firm, which deals in the business of selling handicrafts items like traditional wooden toys, Moonj baskets, rice bowls and vermilion boxes, in both business-to-business (B2B) and business-to-consumer (B2C) markets. Incorporated as a non-governmental organization (NGO) in the year 2014, “Rekhaakriti” was founded with the purpose of preserving, promoting and advancing the Moonj handicraft. Throughout its formative years, the organization experienced several organizational and operational challenges and got almost on the edge of collapse. The dilemma that surrounded Rekha Sinha, a key founding member of “Rekhaakriti”, was whether to carry or dissolve the organization. But, after much contemplation, she decided to convert the organization to a sole proprietorship firm in the year 2017. However, the restructuring decision was also proving to become less effective in attaining the objectives for which the firm got established. This led the owner, Rekha Sinha, to further dug deep to identify obstacles (both internal and external) that impede her firm’s expansion and growth. This case narrates Rekha Sinha's intricate entrepreneurial path in building an innovative handicraft organization and explains how she overcame the overall organizational and operational obstacles. The case provides the context for students to assume the role of protagonist and explore creative strategies for overcoming market obstacles through upskilling, design intervention and product innovation.

Complexity academic level

The case study is intended for the students pursuing their graduation and post-graduation courses in business, management studies, marketing and entrepreneurship. The case also provides suitable insights to management trainees and executives.

Supplementary material

Teaching notes are available for educators only.

Subject code

CSS 8: Marketing.