Biology subjects

Irish, J.

Publications and source records attributed to Irish, J..

6 recordsLinked to original sources

bioRxiv2024

Ancient Borrelia genomes document the evolutionary history of louse-borne relapsing fever

Several disease-causing bacteria have transitioned from tick-borne to louse-borne transmission, a process associated with increased virulence and genome reduction. However, the historical time frame and speed of such evolutionary transitions have not been documented with ancient genomes. Here, we discover four ancient cases of Borrelia recurrentis, the causative agent of louse-borne relapsing fever, in Britain between [~]600 and 2,300 years ago, and sequence whole genomes up to 29-fold coverage. We estimate a recent divergence from the closest tick-borne ancestor, likely within the last [~]8,000 years. We reconstruct a chronology of gene losses and acquisitions using the pan-genome of related species, and show that almost all of the reductive evolution observed in B. recurrentis had occurred by [~]2,000 years ago, and was thus a rapid process after divergence. Our observations provide a new understanding of the origins of B. recurrentis and document complex reductive evolution in a specialist vector-borne pathogen.

evolutionary biology↗

bioRxiv2024

Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19

The variable etiology of persistent breathlessness after COVID-19 have confounded efforts to decipher the immunopathology of lung sequelae. Here, we analyzed hundreds of cellular and molecular features in the context of discrete pulmonary phenotypes to define the systemic immune landscape of post-COVID lung disease. Cluster analysis of lung physiology measures highlighted two phenotypes of restrictive lung disease that differed by their impaired diffusion and severity of fibrosis. Machine learning revealed marked CCR5+CD95+ CD8+ T-cell perturbations in mild-to-moderate lung disease, but attenuated T-cell responses hallmarked by elevated CXCL13 in more severe disease. Distinct sets of cells, mediators, and autoantibodies distinguished each restrictive phenotype, and differed from those of patients without significant lung involvement. These differences were reflected in divergent T-cell-based type 1 networks according to severity of lung disease. Our findings, which provide an immunological basis for active lung injury versus advanced disease after COVID-19, might offer new targets for treatment.

immunology↗

bioRxiv2020

Post-intervention Epidemiology of STH in Bangladesh: data to sustain the gains

IntroductionIn 2008, Bangladesh initiated Preventive Chemotherapy (PCT) for school-age children (SAC) through bi-annual school-based mass drug administration (MDA) to control Soil-Transmitted Helminth (STH) infections. In 2016, the Ministry of Health and Family Welfares Program on Lymphatic Filariasis Elimination and STH (ELFSTH) initiated district-level community impact assessments with Children Without Worms (CWW) using standardized, population-based sampling to measure the post-intervention STH burden across all ages ([≥] 1 yr) for the three STH species. Methods & Principal FindingsThe Integrated Community-based Survey for Program Monitoring (ICSPM) was developed by CWW and was used to survey 12 districts in Bangladesh from 2017 - 2020. We combined the individual demographic and parasite-specific characteristics from 10 districts and linked them with the laboratory data for collective analysis. Our analysis identified district-specific epidemiologic findings, important for program decisions. Of the 17,874 enrolled individuals, 10,824 (61%) provided stool samples. Overall, the prevalence of any STH species was substantially reduced to 14% from 79.8% in 2005. The impact was similar across all ages. STH prevalence was below 10% in 10 districts collectively, but remained high in 4 districts, despite their high reported PCT coverage in previous years. Among all, Bhola district was unique because it was the only district with high Trichuris prevalence. ConclusionBangladesh successfully lowered STH prevalence across all ages despite targeting SAC only. Data from the survey indicate significant number of adults and pre-school age children (PSAC) were self-deworming with purchased pills. This may account for the flat impact curve across all ages. Overall prevalence varied across surveyed districts, with persistent high transmission in the northeastern districts and a district in the central flood zone, indicating possible service and ecological factors. Discrepancies in the impact between districts highlight the need for district-level data to evaluate program implementation after consistent high PCT coverage. Authors SummaryBangladesh government conducted school-based mass drug administration (MDA) for over 10 years to control soil-transmitted helminth (STH) infections. School-based evaluations of MDA indicate a reduction in STH burden among school-aged children (SAC). To further assess the impact on the community, Children Without Worms and the Ministry of Health and Family Welfares Program on Lymphatic Filariasis Elimination and STH (ELFSTH) initiated district-level community impact surveys in 12 districts. We share the results from the latter 10 districts here. Our analysis of 10,824 interviews and stool samples from 10 districts showed an estimated 14% of community members infected with at least one species of STH. This finding is substantially lower than the baseline STH prevalence (79.8%) estimated in 2005. Bangladeshs successful impact was achieved across all ages despite only treating SAC. Deworming source data showed significant numbers of adults and pre-school age children (PSAC) self-dewormed with locally purchased pills. Prevalence varied across the surveyed districts, with persistent high transmission in the northeastern districts and a district in the central flood zone, indicating possible ecological and service factors contributing to persistent infections. Discrepancies in the impact across districts highlights the need for sub-national level data to evaluate program performance fllowing consistent high intervention.

scientific communication and education↗

bioRxiv2020

High-Dimensional mass cytometry analysis reveals systemic immune perturbations in paediatric cancer influenced by age

Systemic immunity plays an important role in cancer immune surveillance and therapy but there is little detailed knowledge about the immune status of healthy children or children with cancer. We performed a high dimensional single cell analysis of systemic immunity in pediatric cancer patients and age-matched healthy children. In young children with cancer (age < 8years) NK cells were decreased in frequency, maturity, expression of perforin and granzyme-B, and were less cytotoxic in ex vivo assays. NK cell activity was restored after in vitro culture with interleukin-2. In contrast, older children with cancer (>8 years old) had decreased naive CD4 and CD8 T-cells with concomitant increases in effector memory and T effector memory RA-revertant (TEMRA) T-cells. These immunological changes in pediatric cancer patients are relevant to the better understanding of how cancers diagnosed in childhood interact with systemic immunity and could inform the development and application of effective immune-modulating therapies in the pediatric population. One Sentence SummaryHigh dimensional analysis of systemic immunity in pediatric cancer patients reveals clinically relevant immune changes in NK and T-cells that vary with patient age.

immunology↗

bioRxiv2017

Root grooves on two adjacent anterior teeth of Australopithecus africanus

Tooth root grooves and other ante-mortem dental tissue loss not associated with caries found on or near the cementoenamel junction (CEJ) are commonly termed non-carious cervical lesions. Three main processes are implicated in forming these lesions: abrasion, dental erosion, and abfraction. As yet, these lesions have not been described in non-Homo hominins. In this study South African fossil hominin collections were examined for evidence of any type of non-carious cervical lesion. Only one individual shows ante-mortem root grooves consistent with non-carious cervical lesions. Two teeth, a mandibular right permanent lateral incisor (STW 270) and canine (STW 213), belonging to the same Australopithecus africanus individual, show clear ante-mortem grooves on the labial root surface. These lesions start below the CEJ, extend over a third of the way toward the apex, and taper to a point towards the lingual side. Microscopic examination revealed no clear directional striations. The shape of these grooves is extremely similar to clinical examples of dental erosion, with the lack of striations supporting this diagnosis. These are the oldest hominin examples of non-carious cervical lesions and first described in a genus other than Homo; further, the lesions suggest that this individual regularly consumed or processed acidic food items.

paleontology↗

bioRxiv2017

Dietary and behavioral inferences from dental pathology and non-masticatory wear on dentitions from a British medieval town

Dental pathology and wear data can provide valuable insights into diet, cultural practices, and the health of populations. In this study, various dental pathologies and types of wear were recorded for 41 individuals (914 permanent teeth), excavated from the medieval cemetery of St. Owens Church in Southgate Street, Gloucester. Teeth were studied macroscopically with a 10x hand lens to confirm the presence of specific pathologies. Relatively high rates of antemortem chipping on the anterior teeth, and the presence of maxillary central incisor notches, suggested that the Gloucester population commonly used their teeth for non-masticatory activities. Abscessing and antemortem tooth loss fell within previously reported ranges for British medieval sites (2.6% and 6% respectively). However, the sample exhibits extremely high levels of carious lesions and calculus. Nearly 24% of teeth have at least one carious lesion, and the presence of calculus was recorded in 74% of teeth within the sample. Overall caries frequency is similar to sites from later time periods. This frequency may reflect Gloucesters location as a large port town. Remains from the same area, but the earlier Roman period, also shows high rates of both caries and calculus, suggesting a continuation of consuming certain cariogenic foods is likely.

pathology↗