Long non-coding RNA profiling of human lymphoid progenitor cells reveals transcriptional divergence of B cell and T cell lineages.

To elucidate the transcriptional 'landscape' that regulates human lymphoid commitment during postnatal life, we used RNA sequencing to assemble the long non-coding transcriptome across human bone marrow and thymic progenitor cells spanning the earliest stages of B lymphoid and T lymphoid specification. Over 3,000 genes encoding previously unknown long non-coding RNAs (lncRNAs) were revealed through the analysis of these rare populations. Lymphoid commitment was characterized by lncRNA expression patterns that were highly stage specific and were more lineage specific than those of protein-coding genes. Protein-coding genes co-expressed with neighboring lncRNA genes showed enrichment for ontologies related to lymphoid differentiation. The exquisite cell-type specificity of global lncRNA expression patterns independently revealed new developmental relationships among the earliest progenitor cells in the human bone marrow and thymus

Gender profile of principal investigators in a large academic clinical trials group

IntroductionGender equity in medicine has become a significant topic of discussion due to consistently low female representation in academia and leadership roles. Gender imbalance directly affects patient care. This study examined the gender and craft group of the Principal Investigators (PI) of clinical trials run by the Australasian Gastro-Intestinal Trials Group (AGITG)MethodsPublicly available data was obtained from the AGITG website. Trials were divided into upper, lower gastrointestinal cancer, miscellaneous (neuroendocrine and gastrointestinal stromal tumours). Where multiple PIs were listed, all were counted. Craft group was assigned as surgical, medical, radiation oncology or other.ResultsThere were 69 trials with 89 PI, where 52 trials were represented exclusively by male PIs. Of all PIs, 18 were women (20.2%); all were medical oncologists. Prior to 2005, all PIs were male. The craft group distribution of PIs was: 79% medical oncologists, 12% surgical oncologists, 8% radiation oncologist, 1% nuclear medicine physicians. Regarding trials with multiple PI's, there were 19 in total. Of these, 11 had only male PIs, which included 5 surgeons. Females were more likely to be a co-PI (42%) as opposed to sole PI (18%). There was no gender policy publicly available on the AGITG website.ConclusionsThere is a low percentage of female PIs in academic oncology trials in the portfolio of this large international trials group. No trial was led by a female surgical or radiation oncologist. There is a need to understand the reasons driving the disparity so that specific strategies can be put in place

The Genotype Specific Competitive Ability Does Not Correlate with Infection in Natural Daphnia magna Populations

Different evolutionary hypotheses predict a correlation between the fitness of a genotype in the absence of infection and the likelihood to become infected. The cost of resistance hypothesis predicts that resistant genotypes pay a cost of being resistant and are less fit in the absence of parasites. The inbreeding-infection hypothesis predicts that the susceptible individuals are less fit due to inbreeding depression.Here we tested if a host's natural infection status was associated with its fitness. First, we experimentally confirmed that cured but formerly infected Daphnia magna are genetically more susceptible to reinfections with Octosporea bayeri than naturally uninfected D. magna. We then collected from each of 22 populations both uninfected and infected D. magna genotypes. All were treated against parasites and kept in their asexual phase. We estimated their relative fitness in an experiment against a tester genotype and in another experiment in direct competition. Consistently, we found no difference in competitive abilities between uninfected and cured but formerly infected genotypes. This was the case both in the presence as well as in the absence of sympatric parasites during the competition trials.Our data do not support the inbreeding-infection hypothesis. They also do not support a cost of resistance, however ignoring other parasite strains or parasite species. We suggest as a possible explanation for our results that resistance genes might segregate largely independently of other fitness associated genes in this system

An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis

Background: Cryptococcal meningitis has high mortality. Flucytosine is a key treatment but is expensive and rarely available. The anti-cancer agent tamoxifen has synergistic anti-cryptococcal activity with amphotericin in vitro. It is off-patent, cheap, and widely available. We performed a trial to determine its therapeutic potential. Methods:Open label randomized controlled trial. Participants received standard care - amphotericin combined with fluconazole for the first two weeks - or standard care plus tamoxifen 300mg/day. The primary end point was Early Fungicidal Activity (EFA) - the rate of yeast clearance from cerebrospinal fluid (CSF). Trial registration https://clinicaltrials.gov/ct2/show/NCT03112031 . Results: 50 patients were enrolled, (median age 34 years, 35 male). Tamoxifen had no effect on EFA (- 0.48log10 colony-forming units/mL/CSF control arm versus -0.49 tamoxifen arm, difference - 0.005log10CFU/ml/day, 95%CI: -0.16, 0.15, P=0.95). Tamoxifen caused QTc prolongation. Conclusion: High dose tamoxifen does not increase the clearance rate of Cryptococcus from CSF. Novel, affordable therapies are needed. Funding:The trial was funded through the Wellcome Trust Asia Programme Vietnam Core Grant 106680 and a Wellcome Trust Intermediate Fellowship to JND grant number WT097147MA

Hypertensive/Microvascular Disease and COPD: a Case Control Study

Background/Aims: This study tested the hypothesis that individuals with chronic obstructive pulmonary disease (COPD) have more small vessel disease and more severe disease than an age- and gender- matched hospital patient comparison group. Methods: This was a single centre, case-control study of 151 individuals with COPD (FEV1/VC) Results: Patients with COPD had more microvascular retinopathy (121, 80% and 76, 50%; OR 3.98, 95%CI 2.39 to 6.64) and more severe disease (42, 28% and 18, 12%; OR 2.85, 95% CI 1.55 to 5.23) than other hospital patients. COPD remained an independent determinant of microvascular retinopathy (OR 4.56, 95%CI 2.49 to 8.36) after adjusting for gender, hypertension, smoking, and diabetes duration. Retinal arterioles and venules were wider in patients with COPD than other hospital patients (mean difference +6.5µm, 95% confidence interval 1.4 to 11.6; and +17.4µm, 95%CI 9.4 to 25.5, respectively). Larger venules were more common in younger individuals (+0.6 µm, 0.1 to 1.17) with more cigarette exposure (+0.3 µm, 0.2 to 0.5) or a lower serum albumin (+23.0 µm, 6.0 to 40.0). Venular calibre was not different in current and former smokers (p=0.77). There were trends for venules to be larger with more severe COPD (lower FEV1/VC, p=0.09) and with CT-demonstrated emphysema (p=0.06). Conclusions: Hypertensive/microvascular disease is more common and more severe in patients with COPD. This is likely to contribute to the associated increase in cardiac risk

Long non-coding RNA profiling of human lymphoid progenitor cells reveals transcriptional divergence of B cell and T cell lineages.

To elucidate the transcriptional 'landscape' that regulates human lymphoid commitment during postnatal life, we used RNA sequencing to assemble the long non-coding transcriptome across human bone marrow and thymic progenitor cells spanning the earliest stages of B lymphoid and T lymphoid specification. Over 3,000 genes encoding previously unknown long non-coding RNAs (lncRNAs) were revealed through the analysis of these rare populations. Lymphoid commitment was characterized by lncRNA expression patterns that were highly stage specific and were more lineage specific than those of protein-coding genes. Protein-coding genes co-expressed with neighboring lncRNA genes showed enrichment for ontologies related to lymphoid differentiation. The exquisite cell-type specificity of global lncRNA expression patterns independently revealed new developmental relationships among the earliest progenitor cells in the human bone marrow and thymus

Application of a membrane photobioreactor combined with microalgae for shrimp culture wastewater treatment

Shrimp farming has emerged as a multi-billion-dollar industry in our country, creating numerous economic benefits. However, this sector has several negative environmental impacts. Recent studies on the utilization of microalgae for wastewater treatment are of current interest due to their environmental remediation ability, as well as their potential to generate economic value from the biomass produced after treatment. This study aimed to evaluate the wastewater treatment efficiency of Chlorella Vulgaris using a PMBR membrane photobiological model in shrimp aquaculture. The evaluation process included an acclimatization phase and a treatment effectiveness evaluation phase, which lasted a total of 101 days. Algae biomass, the removal efficiency of COD, N-NO -, N-NO -, N-NH +, and P-PO 3-, and membrane fouling behavior were analyzed. The initial results demonstrated that the algae were well-adapted to shrimp aquaculture wastewater. The removal efficiency of N-NO -, N-NO -, N-NH +, and P-PO 3- and COD was 88.55%, 76.15%, 84.58%, 78.07%, and 81.33%, respectively. The algae biomass steadily increased from 91.3 mg/L to 327.69 mg/L, reaching an average level of about 208 mg/L. Additionally, the transmembrane pressure (TMP) evaluation indicated that the necessary time for membrane fouling removal was approximately 25-26 days