bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene protein sequence evolution can predict the rapid divergence of ovariole numbers inDrosophila
Authors: Whittle Carrie A. , Extavour Cassandra G.
Published: September 2023

Ovaries play key roles in fitness and evolution: they are essential female reproductive structures that develop and house the eggs in sexually reproducing animals. InDrosophila, the mature ovary contains multiple tubular egg-producing structures known as ovarioles. Ovarioles arise from somatic cellular structures in the larval ovary called terminal filaments, formed by terminal filament cells and subsequently enclosed by sheath cells. As in many other insects, ovariole number per female varies extensively inDrosophila. At present however, there is a striking gap of information on genetic mechanisms and evolutionary forces that shape the well-documented rapid interspecies divergence of ovariole numbers. To address this gap, here we studied genes associated withD. melanogasterovariole number or functions based on recent experimental and transcriptional datasets from larval ovaries, including terminal filaments and sheath cells, and assessed their rates and patterns of molecular evolution in five closely related species of themelanogastersubgroup that exhibit species-specific differences in ovariole numbers. From comprehensive analyses of protein sequence evolution (dN/dS), branch-site positive selection, expression specificity (tau) and phylogenetic regressions (PGLS), we report evidence of 42 genes that showed signs of playing roles in the genetic basis of interspecies evolutionary change ofDrosophilaovariole number. These included the signalling genesupd2andIlp5and extracellular matrix genesvkgandCol4a1, whose dN/dS predicted ovariole numbers among species. Together, we propose a model whereby a set of ovariole-involved gene proteins have an enhanced evolvability, including adaptive evolution, facilitating rapid shifts in ovariole number amongDrosophilaspecies.

Significance Statement

Ovaries inDrosophila, like in other insects, contain egg producing structures, known as ovarioles. The number of ovarioles per female varies amongDrosophilaspecies, but little is known about the genes and evolutionary dynamics that may shape interspecies changes in ovariole numbers. Here, useda prioriexperimental and transcriptome data fromD. melanogasterto identify genes involved in ovariole formation and functions, and studied their molecular evolution among its closely related species within themelanogastersubgroup. Using a multi-layered analysis consisting of protein sequence divergence (dN/dS), adaptive evolution, expression breadth, and phylogenetic regressions, we identified 42 genes whose molecular evolution patterns were well linked to ovariole numbers divergence. Further, gene protein sequence divergence was often predictive of species ovariole numbers.
Performance comparison of Accucopy, Sequenza, and ControlFreeC
Authors: Fan Xinping , Huang Yu S.
Published: September 2023

Copy number alterations (CNAs) are an important type of genomic aberrations. It plays an important role in tumor pathogenesis and progression of cancer. It is important to detect regions of the cancer genome where copy number changes occur, which may provide clues that drive cancer progression. Deep sequencing technology provides genomic data at single-nucleotide resolution and is considered a better technique for detecting CNAs. There are currently many CNA-detection algorithms developed for whole genome sequencing (WGS) data. However, their detection capabilities have not been systematically investigated. Therefore, we selected three algorithms:Accucopy, Sequenza, andControlFreeC, and applied them to data simulated under different settings. The results indicate that: 1) the correct inference of tumor sample purity is crucial to the inference of CNAs. If the tumor purity is wrongly inferred, the CNA detection will fail. 2) Higher sequencing depth and abundance of CNAs can improve performance. 3) Under the settings tested (sequencing depth at 5X or 30X, purity from 0.1 to 0.9, existence of subclones or not), Accucopy is the best-performing algorithm overall. For coverage=5X samples, ControlFreeC requires tumor purity to be above 50% to perform well. Sequenza can only perform well in high-coverage and more-CNA samples.
Genetic basis and evolution of structural color polymorphism in an Australian songbird
Authors: Sin Simon Yung Wa , Ke Fushi , Chen Guoling , Huang Pei-Yu , Enbody Erik , Karubian Jordan , Webster Michael S. , Edwards Scott V.
Published: September 2023

Island organisms often evolve phenotypes divergent from their mainland counterparts, providing a useful system for studying adaption under differential selection. Some island birds have melanic plumage differing from the color of mainland conspecifics, a trait proposed as an insular adaptation. In the white-winged fairywren (Malurus leucopterus), subspecies on two islands have a black nuptial plumage whereas the subspecies on the Australian mainland has a blue nuptial plumage. The black subspecies have a feather nanostructure that could produce a blue structural color, suggesting a blue ancestor. An earlier study proposed independent evolution of melanism on the islands based on the history of subspecies divergence. However, the genetic basis of melanism and the origin of color differentiation in this group are still unknown. Here, we used whole-genomes to investigate the genetic basis of melanism by comparing the blue and blackM. leucopterussubspecies to identify highly divergent genomic regions. We identified a well-known pigmentation geneASIPand four candidate genes that may contribute to feather nanostructure development. We also detected signatures of a selective sweep in genomic regions containingASIPandSCUBE2not in the black subspecies, as predicted by earlier work, but in the blue subspecies, which possesses many derived SNPs in these regions, suggesting that the mainland subspecies has re-evolved a blue plumage from a black ancestor. This re-evolution was likely driven by a pre-existing female preference. Our findings provide new insight into the evolution of plumage coloration in island versus continental populations, and, importantly, we identify candidate genes that likely play roles in the development and evolution of feather structural coloration.
Whole mitogenome analysis highlights demographic history and shared connections among distal Indigenous groups of Mexico Complete mitogenome sequencing from 60 Mexican Native American groups
Authors: Flores-Huacuja Marlen , Snow Meradeth , Ramos-Madrigal Jazmín , Contreras-Cubas Cecilia , Barajas-Olmos Francisco , González-Oliver Angélica , Mendoza-Caamal Elvia , Cicerón-Arellano Isabel , Centeno-Cruz Federico , Córdova Emilio J. , Baca Paulina , Flores-Martínez Silvia Esperanza , Ortiz-López Rocío , Reynolds Austin W. , Kostic Aleksandar David , Villafan-Bernal José Rafael , Galaviz-Hernández Carlos , García-Zapién Alejandra Guadalupe , Miranda-Ortíz Haydee , Lazalde-Ramos Blanca Patricia , Loeza-Becerra Francisco , Carnevale Alessandra , Rangel-Villalobos Héctor , Sosa-Macías Martha , Rojas-Martinez Augusto , Martínez-Hernández Angélica , García-Ortiz Humberto , Orozco Lorena
Published: September 2023

The study of mitochondrial DNA is a valuable tool to delve into the demographic history of human populations. Particularly in the Americas, five widespread Native American specific mitochondrial lineages have been identified. Here we included the complete mitogenome sequencing of 572 Indigenous individuals belonging to 60 populations spanning the Mexican territory. Our results show a great diversity of matrilineages widespread across the country, revealing shared mtDNA haplogroups in populations from distant regions. We identified all the five main Native American haplogroups clades, including 83 different subhaplogroups, from which nine are novel. The most frequent of the novel haplogroups was A2+64. A phylogenetic inference suggests that A2+64 comes from an ancestral maternal lineage that spread into the Caribbean islands. Additionally, a demographic reconstruction from whole mitogenomes showed an exponential increase in female Ne around 10 Ka ago in all the tested regions. All these findings suggest a genetic persistence through Mexico and possibly the Americas, in agreement with the model of the Mesoamerican-related expansion into the Caribbean and South America.
A dynamic Boolean model of molecular and cellular interactions represents psoriasis development and predicts drug candidates
Authors: Tsirvouli Eirini , Noël Vincent , Flobak Åsmund , Calzone Laurence , Kuiper Martin
Published: September 2023

Psoriasis is a chronic skin disease affecting 2-3% of the global population. Psoriasis arises from complex interactions between keratinocytes and immune cells, leading to uncontrolled inflammation, immune hyperactivation and perturbed keratinocyte life cycle. Although the latest generation of drugs have greatly improved psoriasis management, the disease remains incurable, and the substantial variability in treatment response calls for novel approaches to comprehend the intricate mechanisms underlying disease development and to discover potential drug targets. In this study, we present a multiscale population model that captures the dynamics of cell-specific phenotypes in psoriasis, integrating discrete logical formalism and population dynamics simulations. Through simulations and network metrics, we identify potential pairwise interventions as alternative treatment options. Specifically, The model predictions suggest that targeting neutrophil activation in conjunction with either PGE2 production or STAT3 signaling shows promise comparable to IL-17 inhibition, which is currently the most used treatment option for moderate and severe cases of psoriasis. Our findings underscore the significance of considering complex intercellular interactions and intracellular signaling cascades in psoriasis, and highlight the importance of computational approaches in unraveling complex biological systems for drug target identification.

Author summary

In our study, we aimed to uncover the complex mechanisms underlying psoriasis and identify potential treatment options. By utilizing a computational model, we simulated the dynamic interactions between different cell types involved in psoriasis, such as immune cells and keratinocytes. Our model predicts that targeting neutrophil activation, combined with either PGE2 production or STAT3 signaling, may yield comparable effectiveness to the current standard treatment for moderate or severe psoriasis, namely IL-17 inhibition. Our study underscores the importance of computational modeling in unraveling the complexities of disease systems and provides a foundation for identifying new candidate treatment options in psoriasis that should be tested in the lab.
Ghost W chromosomes and unique genome architecture in ghost moths of the family Hepialidae
Authors: Chung Voleníková Anna , Sahara Ken , Štundlová Jana , Dalíková Martina , Koutecký Petr , Grof-Tisza Patrick , Simonsen Thomas J. , Žurovec Michal , Provazníková Irena , Walters James R. , Marec František , Nguyen Petr
Published: September 2023

The classical model of sex chromosome evolution has been recently challenged in moths and butterflies (Lepidoptera). According to the current hypothesis, the adoption of a supernumerary chromosome may have driven the transition from the Z0 to the WZ sex chromosome system in females. However, the evolutionary history of the W chromosome remains enigmatic, especially in the early-diverging lepidopteran lineages. In ghost moths of the family Hepialidae, one of the most basal lepidopteran clades, there is conflicting evidence regarding their sex chromosomes. In this study, we aimed to clarify the status of the hepialid W chromosome. Using cytogenetics and genomics, we investigated the karyotype, sex chromosomes, genome size and repeatome of multiple ghost moth species and reconstructed basic phylogenetic relationships in the group. Our data show that Hepialidae have unusually large genomes (reaching up to 1C = 3 Gb) and are the oldest known lepidopteran clade with a W chromosome. However, the W does not form a typical heterochromatin body in polyploid nuclei, known as sex chromatin, previously employed to detect the presence of W chromosomes across Lepidoptera. Moreover, in some species, the W does not exhibit distinct repeat content and can escape detection via methods that rely on W-specific sequences. Analysis of the Z chromosome confirmed highly conserved gene content, arguing for a possible origin of the hepialid W chromosome from a B chromosome. We hypothesize that the mechanism underlying the formation of sex chromatin could be used in future research to study the origin of the W chromosome.
The mediating role of trust in physicians on the association between multidimensional health literacy and medication adherence in hemodialysis: A cross-sectional study
Authors: Inanaga Ryohei , Toida Tatsunori , Aita Tetsuro , Kanakubo Yusuke , Ukai Mamiko , Toishi Takumi , Kawaji Atsuro , Matsunami Masatoshi , Okada Tadao , Munakata Yu , Suzuki Tomo , Kurita Noriaki
Published: September 2023

Rationale & Objective

Basic health literacy (HL) and trust in physicians can influence medication adherence (MA) in dialysis patients. However, how high-order HL is associated with MA, and how trust in physicians mediates this association remain unclear. We assessed the interrelationships between HL, trust in physicians, and MA, and investigated the mediating role of trust in physicians in the relationship between HL and MA.

Study Design

Multicenter cross-sectional study.

Setting & Participants

Japanese adults receiving outpatient hemodialysis at six dialysis centers.

Exposures

Multidimensional HL was measured using the 14-item Functional, Communicative, and Critical Health Literacy Scale. Trust in physicians was measured using the five-item Wake Forest Physician Trust Scale.

Outcome

MA was measured using the 12-item Adherence Starts Knowledge (ASK-12) scale.

Analytical Approach

A series of general linear models was created to analyze the associations between HL and ASK-12 scores with and without trust in physicians. Mediation analysis was performed to determine whether trust in physicians mediated this association.

Results

In total, 455 patients were analyzed. Higher functional and communicative HL were associated with lower barriers to MA (per 1-point increase: -1.90 (95% confidence interval (CI): -2.67, -1.13) and -2.11 (95% CI: -3.35, -0.87), respectively), whereas higher critical HL was associated with higher barriers (per 1-point increase: 1.67 (95% CI: 0.43, 2.90)). After controlling for trust in physicians, the magnitude of the association between HLs and MA decreased. Trust in physicians partially mediated the association between functional or communicative HL and MA (especially “beliefs”) and completely mediated the association between critical HL and MA (especially “behaviors”).

Limitation

Possible reverse causation.

Conclusions

In addition to functional HL, communicative and critical HL were associated with MA, and their associations were mediated by trust in physicians. To effectively improve MA, individualized strategies for each HL and favorable physician–patient interactions are important.
Chronotype is Associated with Sleep Quality in Older Adults
Authors: Sauers Scott C. , Toedebusch Cristina D. , Richardson Rachel , Spira Adam P. , Morris John C. , Holtzman David M. , Lucey Brendan P.
Published: September 2023

Introduction

Disrupted sleep is common in individuals with Alzheimer’s disease (AD) and may be a marker for AD risk. The timing of sleep or chronotype affects sleep-wake activity and is also associated with AD, but little is known about links between sleep and chronotype in older adults. In this study, we tested if different measures of sleep and chronotype are associated among older adults even after adjusting for multiple potentially confounding variables.

Methods

Participants (N=243) with a mean age of 74 underwent standardized cognitive assessments, measurement of CSF AD biomarkers, and sleep monitoring via single-channel EEG, actigraphy, and self-reported sleep logs. Chronotype was defined as the midpoint of sleep measured by actigraphy.

Results

Later mid-point of sleep (i.e., late chronotype) was associated with African American race and greater night-to-night variability in the sleep mid-point. After controlling for age, race, sex, cognitive status, AD biomarkers, and sleep disorders, a later mid-point of sleep was associated with longer rapid eye movement (REM) onset latency, decreased REM sleep time, lower sleep efficiency, increased sleep onset latency, and more awakenings at night. Late chronotype was also associated with increased <2 Hz non-REM slow-wave activity.

Conclusions

To identify individuals at risk for cognitive impairment before symptoms onset, non-invasivein vivomarkers of brain function, such as sleep, are needed to track both future risk of cognitive impairment and response to interventions. Chronotype is a potential modifiable AD risk factor and should also be taken into account when using sleep as a marker for AD risk.
Deep learning classification ofex vivohuman colon tissues using spectroscopic OCT
Authors: Kendall Wesley Y. , Tian Qinyi , Zhao Shi , Mirminachi Seyedbabak , Joseph Abel , Dufault Darin , Shi Chanjuan , Roper Jatin , Wax Adam
Published: September 2023

Screening programs for colorectal cancer (CRC) have had a profound impact on the morbidity and mortality of this disease by detecting and removing early cancers and precancerous adenomas with colonoscopy. However, CRC continues to be the third leading cause of cancer-related mortality in both men and woman, partly because of limitations in colonoscopy-based screening. Thus, novel strategies to improve the efficiency and effectiveness of screening colonoscopy are urgently needed. Here, we propose to address this need using an optical biopsy technique based on spectroscopic optical coherence tomography (OCT). The depth resolved images obtained with OCT are analyzed as a function of wavelength to measure optical tissue properties. The optical properties can be used as input to machine learning algorithms as a means to classify adenomatous tissue in the colon. In this study, biopsied tissue samples from the colonic epithelium are analyzedex vivousing spectroscopic OCT and tissue classifications are generated using a novel deep learning architecture, informed by machine learning methods including LSTM and KNN. The overall classification accuracy obtained was 88.9%, 76.0% and 97.9% in discriminating tissue type for these methods. Further, we apply an approach using false coloring ofen faceOCT images based on SOCT parameters and deep learning predictions to enable visual identification of tissue type. This study advances the spectroscopic OCT towards clinical utility for analyzing colonic epithelium for signs of adenoma.
Differentiation and Expansion of Tumor-Infiltrating T Cell Clonotypes Occurs in the Spleen Following Immune Checkpoint Blockade
Authors: Morgan Duncan M. , Horton Brendan L. , Zagorulya Maria , Love J. Christopher , Spranger Stefani
Published: September 2023

Immune checkpoint blockade (ICB) enhances tumor-reactive T cell responses against cancer, leading to long-term tumor control and survival in a fraction of patients. Given the increasingly recognized complexity of T cell differentiation that occurs in response to chronic antigen stimulation, it remains unclear precisely which T cell differentiation states are critical for the response to ICB, as well as the anatomic sites at which ICB-mediated reinvigoration of these T cells occurs. We used paired single-cell RNA and T cell receptor (TCR) sequencing to profile endogenous, tumor-reactive CD8+T cells isolated from tumors, tumor-draining lymph nodes, and spleens of mice treated with ICB. We identified an intermediate-exhausted population of T cells in the spleen which underwent the greatest expansion in response to ICB and gave rise to the majority of tumor-infiltrating clonotypes. Increasing concentrations of antigen in the spleen perturbed the differentiation of this phenotype towards a divergent exhausted_KLR state, resulting in reduced numbers of tumor-infiltrating T cells and blunted ICB efficacy. Likewise, an analogous population of exhausted_KLR CD8+T cells in matched human tumor and blood samples and exhibited diminished tumor-trafficking ability. These data demonstrate that the spleen is a critical anatomic site for coordinating the differentiation of tumor-infiltrating clonotypes and their expansion in response to ICB.
Four chromosomally clustered class-C β-lactamases (blaAmpH1/2/3/4) control the cephalosporin hydrolysis inMycobacterium tuberculosisand similar genetic loci appeared as pseudogenes inMycobacterium leprae
Authors: Chakraborty Asit Kumar
Published: September 2023

Mycobacterium tuberculosis(Mt) chromosomal ten PBPs and one class-A β-lactamase (blaC) were implicated in multi-drug resistance against penicillin, cephalosporin and carbapenem drugs. TheE. coliClass-A PBP1A and PBP1B proteins referred as PonA1 and PonA2 inMtwith 34% homologies whereas Class-B PBP2 referred as PbpA and PbpB sub-class proteins with 27% homologies. The class-C PBPs were, PBP4, MecA_N, DacB1, DacB2 and AmpH1- AmpH4. During database search, we found that manyMtPbp4 had no homology toE. coliPBP4 and such enzyme were found to be AmpH class with AmpC, ACC, DHA and GES β- lactamases similarities although one of such enzymes suggested as AmpH but the other referred as DacB or PBP5 in the literature. We investigated theMtwhole genomes (accession nos. AL123456, CP001642, CP054013, CP001641, CP025597) to get authentic PBP4 inMtstrain FDAARGOS_757 genome (protein id. AUP69687, 34% homology toE. coliPBP4) which was designated as conserved protein in chromosomes ofMtstrains H37Rv, H37Rv-1, GG-36-11 and CCDC5180 making confusion in data analysis. Similarly, we BLASTP homology searched with plasmid-mediated 24 β-lactamases suggested that fourblaAmpH genes, (AmpH1, AmpH2, AmpH3andAmpH4) predominantly control the degradation of cephalosporins inM. tuberculosisbut such genes were found as pseudogenes inM. leprae. TheMtAmpH1/2/3/4 enzymes had better homologies withV. parahaemolyticusandYersinia pekkaneniiAmpH enzyme as well as withE. coliAmpH enzyme. The DacB1 (PBP6) and DacB2 (PBP7) enzymes had blaTEM similarity but no AmpH similarity indicating blaC and DacB1/B2 controlled the Penicillin hydrolysis inMt. The blaC enzyme had 30% homology toS. aureusblaZ β-lactamase but such enzyme was also missing inM. leprae. Homology search suggested that carbapenem hydrolysis by blaOXA-23/51-like PBPA/B enzymes and blaOXA-58 related MecA_N domain β-lactamase which has 21% similarity toS. aureusmecA enzyme. The PonA1/A2 had no homology to 24 classes of β-lactamases but still were popular enzymes implicated for better penicillin hydrolysis. We designed primers forMtPBPs to check transcription of individual genes by RT-PCR as well as to check chromosomal locus by BLASTN search after WGS. TheE. coligenome had no similarities toblaAmpH1/2/3/4 genes but a 17nt (5’- CCTTGGTGCCGTCGACC-3’) sequence found in pKEC-a3c plasmid ofC. fruendiiwith homology toblaAmpH4 gene (nt. 1236-1252) and shared a homology with IS1182-like ISKpn6 transposase of plasmids. The oligonucleotides selected manyMtchromosomes and located conserved blaAmpH4 protein in all cases. However, D435E and F495V mutations in theMtstrain 5521 blaAmpH4 were evident and frameshift deletions located inMtstain FDAARGOS_756blaAmpH4 gene with no protein was made. Thus, mutations, deletions and rearrangements mediated by IS-elements were the driving force to make newAmpHgenes inM. tuberculosis.
Influenza A virus H1N1-derived circNP37 positively regulates viral replication by sponging host miR-361-5p
Authors: Zhu Chunyu , Wang Jingyu , Du Yalan , Li Chunli , Hao Mengchan , Zhang Yu , Zhang Xiaoqing , Guan Yiwei , Zheng Fangliang , Zhang Yuan , Chen Jianjun
Published: September 2023

RNA viruses, such as respiratory syncytial virus and SARS-CoV-2, can generate viral circular RNAs (circRNAs), which may play important roles during viral infection. However, whether influenza A viruses have this ability to generate viral circRNAs remains unknown. In this study, we discovered that the negative-strand RNA of the H1N1 nucleoprotein (NP) gene can generate a circRNA, designated circNP37. Furthermore, we demonstrated that circNP37 positively regulated viral replication by competitively sponging host miR-361-5p which inhibited polymerase basic protein 2 (PB2) expression. These results were confirmed using in vivo experiments. Compared with wild-type virus, infection with circNP37 knockout virus resulted in a reduced viral load in the lungs. This study demonstrates, for the first time, the existence and biological function of H1N1-derived circNP37. These findings help us better understand the mechanisms of influenza virus replication and pathogenicity.

Highlights

Negative-strand RNA of the H1N1 nucleoprotein gene can generate a circRNA

CircNP37 plays important roles in viral replication and viral-host interactions

CircNP37 positively regulates replication by competitively sponging host miR-361-5p

eTOC Blurb

In this study, we found that influenza A virus H1N1 infection can generate virus-derived circRNA, circNP37. We also demonstrated that circNP37 positively regulate viral PB2 gene expression and viral replication via sponge host miR-361-5p during viral infection.
The impact of chemical pollution across major life transitions: a meta-analysis on oxidative stress in amphibians
Authors: Martin Colette , Capilla-Lasheras Pablo , Monaghan Pat , Burraco Pablo
Published: September 2023

Among human actions threatening biodiversity, the release of anthropogenic chemical pollutants -which have become ubiquitous in the environment- is a major concern. Chemical pollution can induce oxidative stress and damage by causing the overproduction of reactive oxygen species (ROS), and affecting the antioxidant system. In species undergoing metamorphosis (∼80% of all extant animal species), antioxidant responses to chemical pollution may differ between pre- and post-metamorphic stages. Here, we meta-analysed (N = 86 studies, k = 2,012 estimates) the impact of chemical pollution on the redox balance across the three major amphibian life stages (embryo, larva, adult). Before metamorphosis, embryos and larvae activate their antioxidant pathways and do not show increased oxidative damage. In contrast, post-metamorphic individuals show unnoticeable antioxidant responses, and a marked oxidative damage in lipids. Also, type of pollutant (i.e., organic vs inorganic) promotes contrasting effects across amphibian life stages. Our findings show a divergent evolution of the redox balance in response to pollutants across life transitions of metamorphosing amphibians, likely linked to the characteristics of each life stage. Further comparative mechanistic approaches to wildlife responses to global changes will improve our understanding of these eco-evo-devo processes.
A new T Cell Receptor in Squamata Reptiles
Authors: Gambón-Deza Francisco
Published: September 2023

Squamata exhibit a loss of genes for the gamma/delta T-lymphocyte receptor chains and a significant decrease in the number of V genes at the TRBV locus. Through genome analysis, I have discovered a new locus that contains V, J, C, and TM genes that have a similar structure to the classical TCR chains. This gene is viable, as demonstrated by the presence of messenger RNAs in the transcriptomes. Analyses using the AlphaFold2 program indicate that the deduced protein chain is associated with the alpha chain of the TCR. I have named this new chain “epsilon,” and it forms a new TCR alpha/epsilon. Evolutionarily, the epsilon chain arose from a duplication of the beta chain gene at the time of the divergence of amphibians and reptiles and has since been specifically maintained in Squamata.
Schizosaccharomyces versatilisrepresents a distinct evolutionary lineage
Authors: Etherington Graham J , Gil Elisa Gomez , Haerty Wilfried , Oliferenko Snezhana , Nieduszynski Conrad A.
Published: September 2023

The fission yeast speciesSchizosaccharomyces japonicusis currently divided into two varieties –S. japonicusvar.japonicusandS. japonicusvar.versatilis. Here we examine the var.versatilisisolate CBS5679. The CBS5679 genome shows 88% coding sequence identity to the reference genome ofS. japonicusvar.japonicusat the coding sequence level, with phylogenetic analyses suggesting that it has split from theS. japonicuslineage 25 million years ago. The CBS5679 genome contains a reciprocal translocation between chromosomes 1 and 2, together with several large inversions. The products of genes linked to the major translocation are associated with “metabolism” and “cellular assembly” ontology terms. We further show that CBS5679 does not generate viable progeny with the reference strain ofS. japonicus. Although CBS5679 shares closer similarity to the “type” strain of var.versatilisas compared to S.japonicus, it is not identical to the type strain, suggesting population structure within var.versatilis. We recommend that the taxonomic status ofS. japonicusvar.versatilisis raised, with it being treated as a separate species,Schizosaccharomyces versatilis.

Take-away

The taxonomic status ofSchizosaccharomyces versatilisis addressed.

S. versatilisdiverged fromS. japonicusaround 25 million years ago.

S. versatilisdoes not produce viable progeny in crosses withS. japonicus.

S. versatilishas a reciprocal translocation between chromosomes 1 and 2.

The Gene Ontology terms for genes in the translocations are enriched for terms connected to “metabolism” and “cellular assembly”.
Difference in Differences analysis evaluates the effects of the Badger Control Policy on Bovine Tuberculosis in England
Authors: Birch Colin P.D. , Bakrania Mayur , Prosser Alison , Brown Dan , Withenshaw Susan M. , Downs Sara H.
Published: September 2023

Persistent tuberculosis (TB) in cattle populations in England has been associated with an exchange of infection with badgers(Meles meles). A badger control policy (BCP) commenced in 2013. Its aim was to decrease TB in cattle by reducing the badger population available to provide a wildlife reservoir for bovine TB. Monitoring data from 52 BCP intervention areas 200-1600 km2in size, starting over several years, were used to estimate the change in TB incidence rate in cattle herds, which was associated with time since the start of the BCP in each area. A Difference in Differences analysis addressed the non-random selection and starting sequence of the areas. Herd incidence rate of TB reduced by 56% (95% Confidence Interval 43-67%) up to the fourth year of BCP interventions, with the largest reductions in the second and third years. There was insufficient evidence to judge whether incidence rate reduced further beyond four years. These estimates are the most precise for the timing of decline in cattle TB associated with interventions primarily targeting badgers. They are within the range of previous estimates from England and Ireland. This analysis indicates the importance of reducing transmission from badgers to reduce the incidence of TB in cattle, noting that vaccination of badgers, fertility control and on farm biosecurity may also achieve this effect.
Telomere-to-telomereSchizosaccharomyces japonicusgenome assembly reveals hitherto unknown genome features
Authors: Etherington Graham J , Wu Pei-Shang , Oliferenko Snezhana , Uhlmann Frank , Nieduszynski Conrad A.
Published: September 2023

Schizosaccharomyces japonicusbelongs to the single-genus class Schizosaccharomycetes, otherwise known as ‘fission yeasts’. As part of a composite model system with its widely studiedS. pombesister species,S. japonicushas provided critical insights into the workings and the evolution of cell biological mechanisms. Furthermore, its divergent biology makesS. japonicusa valuable model organism in its own right. However, the currently available short-read genome assembly contains gaps and has been unable to resolve centromeres and other repeat-rich chromosomal regions. Here we present a telomere-to-telomere long-read genome assembly of theS japonicusgenome. This includes the three megabase-length chromosomes, with centromeres hundreds of kilobases long, rich in 5S ribosomal RNAs, transfer RNAs, long terminal repeats, and short repeats. We identify a gene-sparse region on chromosome 2 that resembles a 331 kb centromeric duplication. We revise the genome size ofS. japonicusto at least 16.6 Mb and possibly up to 18.12 Mb, at least 30% larger than previous estimates. Our whole genome assembly will support the growingS. japonicusresearch community and facilitate research in new directions, including centromere and DNA repeat evolution, and yeast comparative genomics.

Take-away

A telomere-to-telomere genome assembly of the fission yeastS. japonicus

Chromosome 2 harbours a previously unknown second centromere-like region

The estimated genome size ofS. japonicusmay be up to 18.12 Mb
Suppressor of Cytokine Signaling 3 Derived Peptide as a Therapeutic for Inflammatory, and Oxidative Stress Induced Damage to the Retina
Authors: Ahmed Chulbul M. , Patel Anil P. , Johnson Howard M. , Ildefonso Cristhian J. , Lewin Alfred S.
Published: September 2023

Purpose

Inflammation and oxidative stress are contributing factors to age-related macular degeneration (AMD) and other retinal diseases. We tested a cell penetrating peptide from the kinase inhibitory region of intracellular checkpoint inhibitor Suppressor of Cytokine Signaling 3 (R9-SOCS3-KIR) peptide for its ability to blunt the inflammatory or oxidative pathways leading to AMD.

Methods

We used Anaphylatoxin C5a to mimic the effect of activated complement, lipopolysaccharide (LPS) and TNFα to stimulate inflammation, and paraquat to induce mitochondrial oxidative stress. We used a human RPE cell line (ARPE-19) as proliferating cells and a mouse macrophage cell line (J774A.1) to follow cell propagation by microscopy or cell titer assays. We evaluated inflammatory pathways by monitoring nuclear translocation of NF-κB p65 and MAP kinase p38, and we used qRT-PCR and Western blots to evaluate induction of inflammatory markers. In differentiated ARPE-19 monolayers, we evaluated the integrity of tight junction proteins by microscopy and measurement of transepithelial electrical resistance. We used intraperitoneal injection of sodium iodate to test the ability of R9-SOC3-KIR to prevent RPE and retinal injury as assessed by fundoscopy, Optical Coherence Tomography (OCT) and histology.

Results

R9-SOCS3-KIR treatment suppressed C5a-induced nuclear translocation of the NF-kB activation domain p65 in undifferentiated ARPE-19 cells. TNF-mediated damage to tight junction proteins in RPE and the loss of transepithelial electrical resistance were prevented in the presence of R9-SOCS3-KIR. R9-SOCS3-KIR prevented the increased expression of genes related to inflammation in response to C5a treatment. R9-SOCS3-KIR also blocked lipopolysaccharide (LPS) induction of cyclooxygenase and inflammatory markers including IL-6, MCP1, COX-1 and IL-1β. R9-SOCS3-KIR prevented paraquat mediated cell death and enhanced the levels of antioxidant effectors. Daily eye drop instillation of R9-SOCS3-KIR protected against retinal injury caused by i.p. administration of sodium iodate.

Conclusion

R9-SOCS3-KIR blocks the induction of inflammatory signaling in cell culture and reduces retinal damage in a widely used model of RPE/retina oxidative injury. Since this peptide can be administered by corneal instillation, this treatment may offer a convenient way to slow the progression of ocular diseases arising from inflammation and chronic oxidative stress.
CATHI: An interactive platform for comparative genomics and homolog identification
Authors: Becker Lukas , Spohr Philipp , Klau Gunnar W. , Axmann Ilka M. , Fraune Sebastian , Schmelling Nicolas M.
Published: September 2023

Abstract

Bioinformatics has established itself as a central pillar of modern biology. Specifically, comparative genomics enables scientists to study a vast number of genomes efficiently. These comparative analyses shed light on the evolution and potential function of genomes and genes, but are also increasingly used as a key tool for metabolic engineering and synthetic biology by identifying appropriate targets for modification. While numerous sophisticated tools for comparative genomics and homolog identification exist, those tools predominantly target highly skilled bioinformatics users. Consequently, many biologists either defer such analyses to their more versed bioinformatic collaborators or resort to suboptimal tools. Here, we present an intuitive solution available on all major operating systems, easily accessed through common web browsers. CATHI – Comparative Analysis Tool for Homolog Identification – integrates a suite of best-practice bioinformatic tools, encompassing BLAST for homology searches, MAFFT for multiple sequence alignment, FastTree2 for phylogeny reconstruction, and clinker for synteny analysis. Specifically tailored to biologists, CATHI orchestrates predefined settings and automated pipelines, obviating the need for programming expertise. This platform empowers researchers to confidently engage in detailed comparative genomics studies by streamlining the analytical process. The interactive framework provides users with a plethora of options. This includes real-time execution and progress monitoring, facilitates dynamic result tracking, and a set of search functions across NCBI databases like CDD or ProtFam. Users can interactively engage in data exploration, filtering, and visualization through CATHI’s intuitive interface. Furthermore, the seamless export of project data in standard formats (FASTA, Newick, CSV, and HTML) facilitates the integration with further third-party tools such as TreeViewer and Jalview. To benchmark CATHI, we revisited the comparative analysis of cyanobacterial circadian clock proteins conducted by Schmelling et al. in 2017, revealing consistent global patterns among identified homologs, while also highlighting individual variations attributed to the expansion of available databases.
Discovery of Natural Bispecific Antibodies: Is Psoriasis Induced by a ToxigenicCorynebacterium simulansand Maintained by CIDAMPs as Autoantigens?
Authors: Schröder Jens-Michael
Published: September 2023

The high abundance ofCorynebacterium simulansin psoriasis skin suggests a contribution to the psoriasis etiology via cell envelope components, which may cause skin inflammation and immune responses. This hypothesis was tested in an exploratory study, where Western Blot (WB) analyses with extracts of heat-treatedC. simulansand psoriasis serum-derived IgG exhibited a single 16 kDa- WB-band. Proteomic analyses revealed, among others, ribosomal proteins as candidateC. s.-antigens. A peptidomic analysis unexpectedly showed that psoriasis-serum-derived IgG already contained 31 immunopeptides originating fromCorynebacteria ssp., suggesting the presence of natural bispecific antibodies (BsAbs). Moreover, peptidomic analyses revealed 372 “DECOY”-peptides with similarity to virus- and phage proteins, includingCorynebacterium diphtheriae phage, and similarity to diphtheria toxin. Strikingly, upon a peptidomic analysis for peptides of human origin, 64 epitopes of major psoriasis autoantigens were identified, which originated from the spacer region of filaggrin, from hornerin repeats, SPINK9, keratin 9, caspase 14, desmoplakin, suprabasin, keratin 2, keratin1, keratin 6C, apolipoprotein A1, a Selene-binding protein, H1.8 linker histone, and the transcription factor BCLAF3. Most identified antigens represent potential “Cationic Intrinsically Disordered Antimicrobial Peptides (CIDAMPs)”, which are generated within the fully differentiated epidermis. These may form complexes with bacterial disordered protein regions, representing chimeric antigens containing discontinuous epitopes. In addition, among 128 low-abundance immunopeptides, 48 are putatively psoriasis-relevant such as epitopes of IL-12, and the receptors of PGE2, vitamin D3, and IL-10. Further, 47 immunopeptides originated from tumor antigens such as CT47A, SDCCAG3, BRCA2, MAGEA6, RNASE4, and the endogenous retrovirus HERV-K. I propose that persistent infection with a toxigenicC. simulansinitiates psoriasis, which is exacerbated as an autoimmune disease by CIDAMPs as autoantigens. The discovery of natural BsAbs allows the identification of antigen epitopes from microbes, viruses, autoantigens, and tumor-antigens, and may help to develop epitope- specific peptide-vaccines and therapeutic approaches with antigen-specific regulatory T cells to improve immune tolerance in an autoimmune disease-specific-manner.
DropBlot: single-cell western blotting of chemically fixed cancer cells
Authors: Liu Yang , Herr Amy E.
Published: September 2023

To further realize proteomics of archived tissues for translational research, we introduce a hybrid microfluidic platform for high-specificity, high-sensitivity protein detection from individual chemically fixed cells. To streamline processing-to-analysis workflows and minimize signal loss, DropBlot serially integrates sample preparation using droplet-based antigen retrieval from single fixed cells with unified analysis-on-a-chip comprising microwell-based antigen extraction followed by chip-based single-cell western blotting. A water-in-oil droplet formulation proves robust to the harsh chemical (SDS, 6M urea) and thermal conditions (98°C, 1-2 hr.) required for sufficient antigen retrieval, and the electromechanical conditions required for electrotransfer of retrieved antigen from microwell-encapsulated droplets to single-cell electrophoresis. Protein-target retrieval was demonstrated for unfixed, paraformaldehyde-(PFA), and methanol-fixed cells. We observed higher protein electrophoresis separation resolution from PFA-fixed cells with sufficient immunoreactivity confirmed for key targets (HER2, GAPDH, EpCAM, Vimentin) from both fixation chemistries. Multiple forms of EpCAM and Vimentin were detected, a hallmark strength of western-blot analysis. DropBlot of PFA-fixed human-derived breast tumor specimens (n = 5) showed antigen retrieval from cells archived frozen for 6 yrs. DropBlot could provide a precision integrated workflow for single-cell resolution protein-biomarker mining of precious biospecimen repositories.
Clusters of multiple long-term conditions in three UK datasets: a latent class analysis
Authors: Steell Lewis , Krauth Stefanie J. , Ahmed Sayem , Dibben Grace , McIntosh Emma , Hanlon Peter , Lewsey Jim , Nicholl Barbara I. , McAllister David , Taylor Rod S. , Singh Sally J. , Mair Frances S. , Jani Bhautesh D.
Published: September 2023

Introduction

Latent class analysis (LCA) can be used to identify subgroups within populations based on unobserved variables. LCA can be used to explore whether certain long-term conditions (LTC) occur together more frequently than others in patients with multiple-long term conditions. In this manuscript we present findings from applying LCA in three large-scale UK databanks.

Methods

We applied LCA to three different UK databanks: Secure Anonymised Information Linkage databank [SAIL], UK Biobank, and Understanding Society: the UK Household Longitudinal Study [UKHLS] and four different age groups: 18-36, 37-54, 55-73, and 74+ years. The optimal number of classes in each LCA was determined using maximum likelihood. Sample size adjusted Bayesian Information Criterion (aBIC) was used to assess model fit and elbow plots and model entropy were used to assess the best number of latent classes in each model.

Results

Between three to six clusters were identified in the different datasets and age groups. Although different in detail, similar types of clusters were identified between datasets and age groups which combine disorders around similar systems incl. Cardiometabolic clusters, Pulmonary clusters, Mental health clusters, Painful conditions clusters, and cancer clusters.
Factors Associated with Malaria Infection in Under Five Children-Zambia, 2018. A Secondary Analysis of the Malaria Indicator Survey, 2018
Authors: Tembo Lindiwe , Sialubanje Cephas , Malasa Martha , Heilmann Elizabeth Susan , Sinyange Nyambe , Nawa Mukumbuta
Published: September 2023

Introduction

Malaria is a public health concern in Zambia. In 2018, Zambia reported a 9% malaria prevalence in under-five children, with some provinces reporting above 20%. Factors still driving malaria infection among the country’s under-five children must be investigated. Factors associated with malaria infection among under-five children were investigated.

Methods

This was a secondary analysis of the cross-sectional study for the Zambia Malaria Indicator Survey 2018 (MIS). Multistage sampling was used in the malaria indicator survey. All children aged 6 to 59 months who received malaria rapid diagnostic tests (RDT) in the data set were considered for the study. Malaria infection: Tested positive or negative for malaria RDT. Sample weights and multivariable logistic regression were used. Backward stepwise regression was used to determine the best model, and the Akaike information criterion was used to select the best model that best fits the data. The Odds ratio measured the association at a 95% confidence level.

Results

A total of 2400 children were analysed. 24.3% (583) tested positive. The median age was 32 (interquartile range (IQR:8-46)) months. Males were 52% (1,249). The odds of malaria infection increased as the child’s age in months increased (aOR=1.004, 95% CI: 1.003, 1.005). Children in the rural had higher odds of malaria than urban children (aOR=1.11,95% CI: 1.05, 1.17). The odds of malaria in children in Copperbelt, Luapula, Muchinga and North-Western Provinces were higher than in children in Central Province (p-value <0.05). Children whose houses did not receive IRS had increased odds of malaria compared to children whose houses received IRS (aOR=1.05, 95%CI: 1.01, 1.09). Sex was not statistically significant.

Conclusion

An increase in age, living in the rural and northern parts of Zambia was associated with malaria infection. Increasing malaria prevention and control measures for older children, rural communities, and the northern parts of Zambia may help reduce malaria prevalence.

Strengths and Limitations

The study used a large dataset of the Malaria Indicator Survey 2018 that was powered to be nationally representative of Zambia, urban and rural strata, and provincial levels.

The study used a complex data analysis considering household weights, census enumeration areas and provinces, addressing intra-cluster correlations.

The study addressed confounding using multivariable regressing and determined the best-fit model using Akaike Information Criteria (AIC) in a backward stepwise regressing.

The study’s main limitation is that it is a survey that simultaneously assessed the outcome and exposure variables, eliciting associations only and not causality.