Recognition and unfolding of human telomeric G-quadruplex by short peptide binding identified from the HRDC domain of BLM helicase

Research in recent decades has revealed that the guanine (G)-quadruplex secondary structure in DNA modulates a variety of cellular events that are mostly related to serious diseases. Systems capable of regulating DNA G-quadruplex structures would therefore be useful for the modulation of various cellular events to produce biological effects. A high specificity for recognition of telomeric G-quadruplex has been observed for BLM helicase. We identified peptides from the HRDC domain of BLM using a molecular docking approach with various available solutions and crystal structures of human telomeres and recently created a peptide library. Herein, we tested one peptide (BLM HRDC peptide) from the library and examined its interaction with human telomeric variant-1 (HTPu-var-1) to understand the basis of G4-protein interactions. Our circular dichroism (CD) data showed that HTPu-var-1 folded into an anti-parallel G-quadruplex, and the CD intensity significantly decreased upon increasing the peptide concentration. There was a significant decrease in hypochromicity due to the formation of G-quadruplex-peptide complex at 295 nm, which indicated the unfolding of structure due to the decrease in stacking interactions. The fluorescence data showed quenching upon titrating the peptide with HTPu-var-1-G4. Electrophoretic mobility shift assay confirmed the unfolding of the G4 structure. Cell viability was significantly reduced in the presence of the BLM peptide, with IC₅₀ values of 10.71 μM and 11.83 μM after 72 and 96 hours, respectively. These results confirmed that the selected peptide has the ability to bind to human telomeric G-quadruplex and unfold it. This is the first report in which a peptide was identified from the HRDC domain of the BLM G4-binding protein for the exploration of the G4-binding motif, which suggests a novel strategy to target G4 using natural key peptide segments.

Schematic representation of (HTPu–var-1-G4) located at the 3′ end, formation of G-quadruplex, model of the G-quadruplex structure, base stacking between G-quadruplex planes, G-quadruplex structure-peptide complex and twisting of G-quadruplex planes upon peptide binding.     

Burkholderia pseudomallei in Environment of Adolescent Siblings with Melioidosis,Kerala, India, 2019

In 2019, Burkholderia pseudomallei was isolated from the backyard of 2 siblings with melioidosis in Kerala, India. This finding highlights the value of healthcare providers being aware of risk for melioidosis in febrile patients, of residents taking precautions when outside, and of increasing environmental surveillance for B. pseudomallei in this region.     

Screening for gestational diabetes,Ahmedabad, India

ObjectiveTo implement a community-based screening and awareness-raising project for gestational diabetes in Ahmedabad, India.MethodsThe project took place between April 2016 and August 2019 in Ahmedabad. Medical college faculty members and medical officers trained 3582 paramedical staff on screening for gestational diabetes. These paramedical staff tested all pregnant women 24–28 weeks gestation, who were attending village health and nutrition days – also called mamta days – in urban and rural health centres for routine antenatal care, for gestational diabetes. An oral glucose tolerance test was used and blood sugar ≥ 7.8 mmol/L was the cut-off for gestational diabetes. Women with gestational diabetes were referred for counselling and treatment and all women were followed until 6 weeks after delivery.FindingsOf 53 522 pregnant women screened, 6786 (12.7%) had gestational diabetes and were referred for nutritional therapy or medication; 836 (12.3%) of these women started medication. There was no significant difference in the prevalence of stillbirths between women with gestational diabetes (0.8%; 54/6786) and women without (0.7%; 338/46 736; P-value: 0.51). Of the women on treatment, 38 had abnormal blood glucose after delivery and continued with the medication. Two women with gestational diabetes died; they had other associated co-morbidities – pre-eclampsia and anaemia.ConclusionWe found a high prevalence of gestational diabetes, indicating the need for gestational diabetes screening and implementation of this project on a larger scale. Gestational diabetes screening at the community level is operationally feasible using the existing human resources and infrastructure of the reproductive health programmes.     

Management of hydatid disease (echinococcosis) in pregnancy

Hydatid disease, manifesting as single or multiple hydatid cysts and caused by Echinococcus granulosus, is common in many parts of the world, especially the tropical countries. Although rare, this disease can also present during pregnancy, especially in endemic areas. Although much has been written about hepatic hydatidosis, there are only a few articles (mainly case reports) on hydatid disease in association with pregnancy. A literature search was done through Medline/PubMed and Medscape independently by the authors from 1950 to 2007 for key words "echinococcosis" and "pregnancy" and "management." All retrieved articles were reviewed. Manual cross-referencing was also done with inclusion of all relevant articles. In this review, we have attempted to summarize the presentation and available management approaches to hydatid disease, and have suggested evidence-based guidelines for its management during pregnancy.     

Furan oligomers and beta-carbolines from terrestrial streptomycetes

2,5-Bis(hydroxymethyl)furan monoacetate (3) and 2,5-bis(hydroxymethyl)furan diacetate (4) were obtained as new natural products from an ethyl acetate extract of the terrestrial Streptomyces sp. isolate GW11/1695. Another Streptomyces isolate, GW21/1313, delivered a dimer (6) and a trimer (7) of (hydroxymethyl)furfural. The latter strain also produced 4-hydroxy-2-(5-(hydroxymethyl)furan-2-ylmethylene)-5-methylfuran-3-one (5), perlolyrin (8), and two new beta-carboline derivatives, 9 and 10. 2,5-Bis(hydroxymethyl)furan diacetate (4) exhibited weak cytotoxic activity against brine shrimp larvae.     

Vitamin D Status among Women in a Rural District of Nepal: Determinants and Association with Metabolic Profile—A Population-Based Study

Hypovitaminosis D is prevalent worldwide, and especially in South-Asia. According to the Institute of Medicine (IOM), 25(OH)D levels below 30 nmol/L are defined as vitamin D deficiency (VDD) and levels between 30–50 nmol/L as insufficiency (VDI). Besides its role in calcium homeostasis, it has been postulated that vitamin D is involved in metabolic syndrome. Given the scarcity of data on vitamin D status in Nepal, we aimed to examine the prevalence of VDD and VDI, as well as the determinants and association with metabolic parameters (lipids, HbA1c), in a cohort of women in rural Nepal. Altogether, 733 women 48.5 ± 11.7 years of age were included. VDD and VDI were observed in 6.3 and 42.4% of the participants, respectively, and the prevalence increased by age. Women reporting intake of milk and eggs > 2 times weekly had higher 25(OH)D levels than those reporting intake < 2 times weekly. Women with vitamin D levels < 50 nmol/L displayed higher levels of cholesterol, LDL-cholesterol, triglycerides, and HbA1c. Additionally, a regression analysis showed a significant association between hypovitaminosis D, dyslipidemia, and HbA1c elevation. In conclusion, VDI was prevalent and increased with age. Milk and egg intake > 2 times weekly seemed to decrease the risk of VDI. Moreover, hypovitaminosis D was associated with an adverse metabolic profile.     

A new non-hormonal antifertility drug DL 111-IT: II. Effects on testicular hyaluronidase activity in male rats

Effects of DL-111, [3-(2-ethylphenyl)-5-(3-methoxyphenyl-1H-1,2,4-triazole] a non-hormonal antifertility agent, on testicular hyaluronidase activity, an accurate biochemical marker for testicular function, were evaluated in male rats. Treatment of 21-day-old rats with DL-111 sc for 7 or 15 days resulted in a significant fall in testicular weight and complete suppression of hyaluronidase activity. During the 30-day post-treatment the enzyme activity was restored to normal levels. Treatment of 40-day-old rats for 7 or 15 days also produced a significant decrease in testicular weight and hyaluronidase activity. Simultaneous administration of LH, PMSG or T with DL-111 to 21-day-old rats blocked the inhibitory activity of the drug as the enzyme activity was restored to untreated control levels. Administration of FSH along with DL-111 had no effect on suppressive action of the drug. These results suggest that in male rats DL-111 inhibits testicular activity by reducing LH levels, thereby reducing T levels as observed by reduced weights of testes and accessory glands of reproduction and hyaluronidase activity.