Investigating the Role of the Planar Cell Polarity (PCP) Protein CELSR1 in Breast Cancer

Planar cell polarity (PCP) is essential for generating highly organized tissue structures and for directional cell movement/migration. The role of PCP in embryogenesis is well-documented, however its role in adult pathologies, such as cancer, is a relatively new field of research. A growing number of publications imply a significant role for PCP proteins in cancer progression and metastasis. PCP is governed by several cytosolic proteins and transmembrane receptors including the G-protein coupled receptor CELSR1. Research studies have raised the hypothesis that CELSR1 acts as a tumour suppressor in breast cancer. Our research aim was to characterise an in-vitro model to understand the molecular/cellular basis of the role of CELSR1 in breast cancer. Computational biology was used to assess CELSR1 expression in breast cancer sub-types and its impact on patient survival. Characterisation of breast cancer cell lines representing increasingly invasive breast cancer was performed through qPCR and western blot analysis to investigate CELSR1 expression and immunocytochemistry to investigate CELSR1 protein distribution. RT-PCR and Sanger sequencing were used to assess differential splicing of the C-terminus of CELSR1. Gain and loss-of-function assays were conducted to test the tumour suppressive functions of CELSR1. Bioinformatics analysis has revealed that CELSR1 expression is increased in the less invasive Luminal A subtype of breast cancer, and that higher expression of CELSR1 has positive impact on overall patient survival. In vitro studies of common breast cancer cell lines revealed that CELSR1 is more highly expressed in less invasive luminal type cell lines, but its expression is reduced in more invasive type cell lines. Furthermore, whilst less invasive breast cancer cell lines exhibit cortical enrichment of CELSR1, CELSR1 becomes localised in intracellular punctate structures adjacent to the nucleus within the highly invasive breast cancer cells. Finally, we find that overexpression of Celsr1 in highly invasive breast cancer cell lines reduces their migratory ability and proliferation. Taken together, our study is consistent with a role for CELSR1 as a tumour suppressor in breast cancer. Future studies will aim to decipher its mechanism of action

Genospecies and virulence factors of Aeromonas species in different sources in a North African country

Introduction: Aeromonads of medical importance have been reported from numerous clinical, food, and water sources, but identification of genospecies and virulence factors of Aeromonas species from countries in North Africa and the Middle East are few.Methods: In total 99 Aeromonas species isolates from different sources (diarrheal children [n=23], nondiarrheal children [n=16], untreated drinking water from wells [n=32], and chicken carcasses [n=28]) in Tripoli, Libya, were included in the present investigation. Genus identification was confirmed by biochemical analysis, and genospecies were determined using a combination of 16S rDNA variable region and gyrB sequence analysis. Polymerase chain reaction (PCR) was used to detect genes encoding toxins from 52 of the isolates.Results: We identified 44 isolates (44%) as A. hydrophila (3 [3.0%] subspecies anaerogenes, 23 [23%] subspecies dhakensis, and 18 [18%] subspecies ranae); 27 isolates (27%) as A. veronii; 23 isolates (23%) as A. caviae; and 5 isolates (5.0%) as other genospecies. The genes encoding aerolysin (aer), cytolytic enterotoxin (act), and A. hydrophila isolate SSU enterotoxin (ast) were detected in 45 (87%), 4 (7.7%), and 9 (17%) of the 52 isolates tested, respectively. The gene encoding an extracellular lipase (alt) was not detected.Conclusion: The majority of aeromonads from Libya fall within three genospecies (i.e. A. hydrophila, A. veronii, and A. caviae), and genes coding for toxin production are common among them.Keywords: Aeromonas; genospecies; virulence factors; Liby

SV2B /miR-34a/miR-128 axis as prognostic biomarker in glioblastoma multiforme

© 2024 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Glioblastoma (GBM) is a heterogenous primary brain tumour that is characterised with unfavourable patient prognosis. The identification of biomarkers for managing brain malignancies is of utmost importance. MicroRNAs (miRNAs) are small, non-coding RNAs implicated in cancer development. This study aimed to assess the prognostic significance of miRNAs and their gene targets in GBM. An in silico approach was employed to investigate the differentially expressed miRNAs in GBM. The most dysregulated miRNAs were identified and analysed via Sfold in association with their gene target. The candidate gene was studied via multi-omics approaches, followed by in vitro and in vivo experiments. The in silico analyses revealed that miR-128a and miR-34a were significantly downregulated within GBM. Both miRNAs displayed high binding affinity to the synaptic vesicle glycoprotein 2B (SV2B) 3′ untranslated region (3′UTR). SV2B exhibited upregulation within brain regions with high synaptic activity. Significantly higher SV2B levels were observed in high grade brain malignancies in comparison to their normal counterparts. SV2B expression was observed across the cytoplasm of GBM cells. Our findings underscored the downregulated expression patterns of miR-128a and miR-34a, alongside the upregulation of SV2B in GBM suggesting the importance of the SV2B/miR-34a/miR-128 axis as a potential prognostic approach in GBM management.Peer reviewe

Clonal Relatedness of Enterotoxigenic Escherichia coli (ETEC) Strains Expressing LT and CS17 Isolated from Children with Diarrhoea in La Paz, Bolivia

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a major cause of traveller's and infantile diarrhoea in the developing world. ETEC produces two toxins, a heat-stable toxin (known as ST) and a heat-labile toxin (LT) and colonization factors that help the bacteria to attach to epithelial cells. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we characterized a subset of ETEC clinical isolates recovered from Bolivian children under 5 years of age using a combination of multilocus sequence typing (MLST) analysis, virulence typing, serotyping and antimicrobial resistance test patterns in order to determine the genetic background of ETEC strains circulating in Bolivia. We found that strains expressing the heat-labile (LT) enterotoxin and colonization factor CS17 were common and belonged to several MLST sequence types but mainly to sequence type-423 and sequence type-443 (Achtman scheme). To further study the LT/CS17 strains we analysed the nucleotide sequence of the CS17 operon and compared the structure to LT/CS17 ETEC isolates from Bangladesh. Sequence analysis confirmed that all sequence type-423 strains from Bolivia had a single nucleotide polymorphism; SNP(bol) in the CS17 operon that was also found in some other MLST sequence types from Bolivia but not in strains recovered from Bangladeshi children. The dominant ETEC clone in Bolivia (sequence type-423/SNP(bol)) was found to persist over multiple years and was associated with severe diarrhoea but these strains were variable with respect to antimicrobial resistance patterns. CONCLUSION/SIGNIFICANCE: The results showed that although the LT/CS17 phenotype is common among ETEC strains in Bolivia, multiple clones, as determined by unique MLST sequence types, populate this phenotype. Our data also appear to suggest that acquisition and loss of antimicrobial resistance in LT-expressing CS17 ETEC clones is more dynamic than acquisition or loss of virulence factors

Toward a more inclusive profession: a qualitative study of female wind band conductors

Women are a minority group in the profession of wind band conducting. The purpose of this study, therefore, is to interview a select group of nationally-recognized women who are wind band conductors to glean insights into their experiences and perspectives. These distinguished women share their motivations, career and life experiences, and advice in non-confidential interviews. The profession of wind band conducting is enlightened by the participants who provided insights and context into their experiences, frames of reference, and viewpoints as women. Three primary themes emerge from the data. Identity-masking and performance attire for female conductors is the first theme. Participants share experiences, wisdom, and opinions to contribute to this complex discussion. In the second theme, the participants describe personal experiences and provide wisdom for navigating both overt and subtle discrimination in the field of music. In the final theme, the participants state a desire to connect with and invest in future generations of women in the conducting profession. The researcher also presents secondary themes that emerge from the data and may be important avenues for future research

PETS E A COVID-19: CÃES E GATOS DOMÉSTICOS E SUAS CONEXÕES COM O NOVO CORONAVÍRUS HUMANO

The Novel Coronavirus SARS-CoV-2 pandemic still raises questions in the scientific community about the source of disease contamination, and confirmation of COVID-19 as a new anthropozoonosis, which seeks to understand the role of animals in the beginning and maintainance of the pandemic cycle. Specially, dogs and cats are of greater concern because of their close, almost uninterrupted, contact with humans sharing the same environment, thus increasing their risk of exposure to the pathogen. In these animals, other strains of coronavirus are known to cause species-specific diseases, such as respiratory canine coronavirus and enteric canine coronavirus in dogs and feline coronavirus in cats. However, both can occasionally cause disease only in other species of non-human animals. Some reports of natural SARS-CoV-2 infection in dogs and cats have been published, as well as investigations into the susceptibility of these species to the virus. International human and animal health surveillance institutions have also commented on the relationship between domestic animals and COVID-19. This review intends to update the reader about SARS-CoV-2 infections in the context of dogs and cats, discussing the connections between these animals and the new human coronavirus and warning about the inappropriate and unnecessary abandonment of these animals during the COVID-19 pandemic.A pandemia do novo coronavírus SARS-CoV-2 ainda causa indagações na comunidade científica, que busca compreender o papel dos animais no ciclo de contaminação como fonte/origem da doença e sobre a confirmação da COVID-19 como uma nova antropozoonose, Especialmente, cães e gatos trazem uma preocupação maior por conta de sua convivência íntima com seres humanos compartilhando o mesmo ambiente, quase que ininterruptamente, aumentando assim seu risco de exposição ao patógeno. Sabe-se que nesses animais outras espécies de coronavírus causam doenças espécie-específicas, como o coronavírus canino respiratório e o coronavírus canino entérico nos cães e o coronavírus felino em gatos, que podem ser transmitidos, ocasionalmente, para outros animais, porém não em humanos. Alguns relatos de infecção natural por SARS-CoV-2 em cães e gatos já foram publicados, bem como investigações sobre a susceptibilidade dessas espécies ao vírus. As instituições internacionais de vigilância em saúde humana e animal também já se pronunciaram a respeito da relação entre animais domésticos e a COVID-19. Esta revisão pretende atualizar o leitor na casuística de infecções por SARS-CoV-2 em cães e gatos de estimação, discutir as conexões entre esses animais e o novo coronavírus humano e alertar sobre o comportamento inoportuno e desnecessário de abandono desses animais durante a pandemia da COVID-19

SV2B/miR-34a/miR-128 axis as prognostic biomarker in glioblastoma multiforme

Data availability: The datasets generated and/or analysed during the current study are available upon reasonable request. Researchers interested in accessing the data can contact the corresponding authors.Supplementary Information is available online at: https://www.nature.com/articles/s41598-024-55917-6#Sec16 .Glioblastoma (GBM) is a heterogenous primary brain tumour that is characterised with unfavourable patient prognosis. The identification of biomarkers for managing brain malignancies is of utmost importance. MicroRNAs (miRNAs) are small, non-coding RNAs implicated in cancer development. This study aimed to assess the prognostic significance of miRNAs and their gene targets in GBM. An in silico approach was employed to investigate the differentially expressed miRNAs in GBM. The most dysregulated miRNAs were identified and analysed via Sfold in association with their gene target. The candidate gene was studied via multi-omics approaches, followed by in vitro and in vivo experiments. The in silico analyses revealed that miR-128a and miR-34a were significantly downregulated within GBM. Both miRNAs displayed high binding affinity to the synaptic vesicle glycoprotein 2B (SV2B) 3′ untranslated region (3′UTR). SV2B exhibited upregulation within brain regions with high synaptic activity. Significantly higher SV2B levels were observed in high grade brain malignancies in comparison to their normal counterparts. SV2B expression was observed across the cytoplasm of GBM cells. Our findings underscored the downregulated expression patterns of miR-128a and miR-34a, alongside the upregulation of SV2B in GBM suggesting the importance of the SV2B/miR-34a/miR-128 axis as a potential prognostic approach in GBM management

Sentinel hospital-based surveillance of Rotavirus diarrhea in Iran

Background. Rotavirus is the most common causes of severe, acute diarrhea during childhood and is an important cause of morbidity and mortality in developing countries. We established active hospital-based surveillance of childhood diarrhea to assess the scope of severe rotavirus disease in Iran. Methods. From May 2006 through April 2007, prospective surveillance of rotavirus diarrhea among children aged <5 years was conducted in 5 sentinel hospitals in Iran. Stool samples were tested for rotavirus using a commercially available enzyme immunoassay, and rotavirus-positive samples were genotyped using reverse-transcriptase polymerase chain reaction. Results. Of 2198 children admitted to the hospital for acute gastroenteritis, 1298 (59.1%) had stool samples test positive for rotavirus by enzyme immunoassay. Of the rotavirus episodes, 85% occurred during the first 2 years of life, with the peak prevalence of severe rotavirus disease occurring from September through January. Among the 110 rotavirus-positive samples that were genotyped, G4P[8] was the most commonly detected rotavirus genotype (30.9% of strains). Other commonly detected genotypes included P[8] with G nontypeable (21.8%), G4 with P nontypeable (13.6%), G1[P8] (10.9%), and G2[P4] (5.5%). Conclusions. Rotavirus is the most common cause of severe diarrhea in Iran, which indicates that safe and effective rotavirus vaccination in Iran is a public health priority. © 2009 by the Infectious Diseases Society of America. All rights reserved