MicroRNA-129-1 acts as tumour suppressor and induces cell cycle arrest of GBM cancer cells through targeting IGF2BP3 and MAPK1

Background MicroRNA-129-1 (miR-129-1) seems to behave as a tumour suppressor since its decreased expression is associated with different tumours such as glioblastoma multiforme (GBM). GBM is the most common form of brain tumours originating from glial cells. The impact of miR-129-1 downregulation on GBM pathogenesis has yet to be elucidated. Methods MiR-129-1 was overexpressed in GBM cells, and its effect on proliferation was investigated by cell cycle assay. MiR-129-1 predicted targets (CDK6, IGF1, HDAC2, IGF2BP3 and MAPK1) were also evaluated by western blot and luciferase assay. Results Restoration of miR-129-1 reduced cell proliferation and induced G1 accumulation, significantly. Several functional assays confirmed IGF2BP3, MAPK1 and CDK6 as targets of miR-129-1. Despite the fact that IGF1 expression can be suppressed by miR-129-1, through 30-untranslated region complementary sequence, we could not find any association between IGF1 expression and GBM. MiR-129-1 expression inversely correlates with CDK6, IGF2BP3 and MAPK1 in primary clinical samples. Conclusion This is the first study to propose miR129-1 as a negative regulator of IGF2BP3 and MAPK1 and also a cell cycle arrest inducer in GBM cells. Our data suggests miR-129-1 as a potential tumour suppressor and presents a rationale for the use of miR-129-1 as a novel strategy to improve treatment response in GBM

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity

Background: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. Methods: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. Results: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0) patients. Two patients (7.7) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7) developed one type of autoimmunity, and 16 patients (59.3) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6). In 13 patients (61.9), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7), gastrointestinal (48.1), rheumatologic (25.9), and dermatologic (22.2) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. Conclusion: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity. © 2020 Georg Thieme Verlag. All rights reserved

Zaprionus indiana (Diptera: Drosophilidae) in Saudi Arabia and the effect of temperature on the life cycle

Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh II451, Saudi ArabiaDuring August and November 1988 a number of drosophilid flies Zaprionus indiana Gupta 1970. were collected from the pomegranate fruit at Taif area in Saudi Arabia. The effects of 25°C, 30°C and 35°C on developmental period and survival of different stages in the life cycle of the fly were investigated at 75% relative humidity and under continuous light. The mean egg incubation period, larval and pupal duration periods and adult longevity decreased with an increase in temperature from 25°C to 30°c. However. the mean hatching percentage, larval and pupal survival, weight of adults, cumulative percentage of adult mortality were increased. The reduction in mean adult longevity at 30°C rather than 25°C was associated with great reduction in the mean oviposition period and fecundity from 35.8 :!: 12.9 to 1.3 :!: 0.9 days; and 112.5 :!: 39.7 to 1.2 :!: 0.9 eggs, respectively, and all eggs laid at 30°C failed to hatch. Most of the eggs oviposited at 25°C were laid days 11 to 25 after emergence. At 35°C only the mean larval duration period was prolonged, but the mean incubation period and larval duration period were decreased, and all pupae failed to develop to an adult. The mean generation life span was 22.4 days at 25°C, shorter than 29.2 days at 30°C