Continuous elimination of oxidized nucleotides is necessary to prevent rapid onset of cellular senescence

Reactive oxygen species (ROS) appear to play a role in limiting both cellular and organismic lifespan. However, because of their pleiotropic effects, it has been difficult to ascribe a specific role to ROS in initiating the process of cellular senescence. We have studied the effects of oxidative DNA damage on cell proliferation, believing that such damage is of central importance to triggering senescence. To do so, we devised a strategy to decouple levels of 8-oxoguanine, a major oxidative DNA lesion, from ROS levels. Suppression of MTH1 expression, which hydrolyzes 8-oxo-dGTP, was accompanied by increased total cellular 8-oxoguanine levels and caused early-passage primary and telomerase-immortalized human skin fibroblasts to rapidly undergo senescence, doing so without altering cellular ROS levels. This senescent phenotype recapitulated several salient features of replicative senescence, notably the presence of senescence-associated beta-galactosidase (SA beta-gal) activity, apparently irreparable genomic DNA breaks, and elevation of p21^Cip1, p53, and p16^INK4A tumor suppressor protein levels. Culturing cells under low oxygen tension (3%) largely prevented the shMTH1-dependent senescent phenotype. These results indicate that the nucleotide pool is a critical target of intracellular ROS and that oxidized nucleotides, unless continuously eliminated, can rapidly induce cell senescence through signaling pathways very similar to those activated during replicative senescence.     

Handedness,Hinduism and sculpture: Searching for evidence of lateralisation

The majority of people throughout the world show extreme preference for the right hand. We studied lateral bias depicted in ancient Indian sculptures dating between the 7th and 9th centuries ad. A total of 288 sculptures were selected from various excavation sites/museums and the frequencies were computed on 13 different criteria in order to see the preferential bias for hand depicted in sculptures of male and female figures. The findings are discussed in the light of Hindu mythology and rituals.     

Complications from “Stem Cell Tourism” in Neurology

“Stem cell tourism,” the practice of offering unproven cellular preparations to patients as approved therapy, is rising in neurology. Currently, the experiences of patients and reported complications from these procedures are unknown in the United States. We evaluate academic neurologists' experiences with stem cell tourism and assess perceived competency on discussing this topic with patients. We found a lack of neurologist preparedness to discuss stem cell therapies with patients and an alarming list of unreported complications from these unregulated procedures. We also identified an urgent need for neurologist education and the creation of a national registry for reporting patient complications resulting from experimental stem cell interventions. ANN NEUROL 2020;88:661–668     

Methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to epilepsy

Background

Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism was reported as risk factor for multiple diseases due to its role in conversion of homocysteine to methionine. The aim of the present meta-analysis was to find out the validity of association of C677T polymorphism with epilepsy susceptibility.

Methods

Pubmed, Science Direct, Springer Link and Google Scholar, databases were searched for relevant studies up to January, 31, 2018. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed using five genetic models. All statistical analysis was done by MetaAnalyst and Mix programs.

Results

Except recessive model, significant association was found between MTHFR C677T polymorphism and epilepsy risk in other four genetic models (T vs C: OR?=?1.29, 95% CI?=?1.08–1.52, p?=?0.004; TT vs CC: OR?=?1.48, 95% CI?=?1.19–1.82, p?=?0.0003; TT + CT vs CC: OR?=?1.20, 95% CI?=?1.05–1.38, p?=?0.008; TT vs CT + CC: OR?=?1.35, 95% CI?=?1.11–1.62, p?=?0.002). Similarly, in the subgroup analysis based on ethnicity, significant association was found in Asian (T vs C: OR?=?1.85; 95% CI?=?1.15–2.99; p?=?0.03) and Caucasian populations (TT vs CC: OR?=?1.38; 95% CI?=?1.10–1.1.73; p?=?0.005). No evidence of heterogeneity and publication bias was detected in present meta-analysis.

Conclusion

In conclusion, results of present meta-analysis suggested that 677T allele of MTHFR is significantly increases the epilepsy susceptibility.

     

Characterization of the complete mitochondrial genome of the giant black Himalayan honeybee (<Emphasis Type="Italic">Apis laboriosa</Emphasis>) from Nepal

The giant black honeybee, Apis laboriosa, has been applied to the highlands of Southeast Asia, where the number of nests has been drastically decreasing. In this study, we first analyzed the complete mitochondrial genome of A. laboriosa from Nepal using Next sequencing technology. The mitochondrial genome is a circular molecule of approximately 1.5 kb, and includes 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and one AT-rich control region. The average AT content of the A. laboriosa mitochondrial genome is 84.7%. Start codons ATG and ATT were found in three and ten genes, respectively, while stop codons TAA and TAG were observed in 12 and 1 gene, respectively. All tRNA genes formed typical cloverleaf secondary structures, except for Ser (AGN) and Gln (Q). The heavy strand (H-strand) was predicted to have 9 PCGs and 14 tRNA genes, while the light strand (L-strand) was predicted to contain four protein-coding, eight tRNA, and two rRNA genes. The 1858 mutation sites that differ between A. laboriosa and Apis dorsata were evenly distributed throughout the mitochondrial genome. The phylogenetic relationship, inferred using 13 PCGs (based on maximum likelihood) was consistent with several previous studies that predicted a sister relationship between A. laboriosa and A. dorsata. A phylogenetic analysis inferred from the 13 mitochondrial PCGs, based on maximum likelihood, indicates that A. laboriosa and A. dorsata are very closely related. We found that the genetic distance between A. laboriosa and A. dorsata is 0.197, indicating that, while they are genetically similar enough to be considered sister species, they are indeed two distinct species.     

Interferon in the treatment of hairy-cell leukemia

The introduction of alpha interferon in 1984 initiated a new and exciting turnaround in the treatment of hairy-cell leukemia. Until that time splenectomy was the only known effective therapy for this disease. Interferon proved to benefit hairy-cell leukemia patients with active disease, whether or not they had undergone prior splenectomy. However, most interferon-induced responses were partial and were of relatively short duration. Purine analogues such as cladribine and pentostatin have since been found to be more effective than alpha interferon and, therefore, have now replaced interferon as first-line therapy for hairy-cell leukemia. At the present time, interferon has a relatively limited role in the treatment of hairy-cell leukemia and it is reserved for a group of selected patients who have failed nucleoside analogue therapy. In this chapter, we discuss the efficacy of interferon and its response duration, toxicity and possible mechanism of action in patients with hairy-cell leukemia.     

HIV/AIDS prevention practices among military personnel in Northwest Ethiopia

ABSTRACT

The spread of HIV/AIDS is a major public health problem in military personnel in Africa. However, the epidemiological evidence regarding HIV/AIDS prevention practices among military personnel in Ethiopia remains unclear. The aim of this study was to investigate HIV/AIDS prevention practices among military personnel in Northwest Ethiopia. A cross-sectional study among military personnel (n?=?410) was conducted in Northwest Ethiopia in 2015. Data were collected using a pre-tested questionnaire. Multivariable logistic regression model was fitted to ascertain factors influencing participation in HIV/AIDS prevention programs. About one-fourth (24.6%) of the military personnel had multiple sexual partners, of whom 24.7% failed to use condoms regularly when having sex with non-regular sexual partners. Majority of the sample (n?=?355, 86.6%) participated in HIV/AIDS prevention programs. Military personnel who had multiple sexual partners were 6.3 times more likely to report history of non-participation in HIV/AIDS prevention programs (AOR?=?6.3, CI₉₅?=?3.5–11.54). A considerable proportion of military personnel had multiple sexual partners with lower levels of condom utilization with non-regular sexual partners. The study further demonstrated misconceptions about HIV/AIDS in Ethiopian military personnel, which reduce their likelihood of participation in HIV/AIDS prevention programs. Health authorities need to strengthen and accelerate HIV/AIDS prevention programs focusing towards military personnel.