Members of the chloride intracellular ion channel protein family demonstrate glutaredoxin-like enzymatic activity

© 2015 Al Khamici et al. The Chloride Intracellular Ion Channel (CLIC) family consists of six evolutionarily conserved proteins in humans. Members of this family are unusual, existing as both monomeric soluble proteins and as integral membrane proteins where they function as chloride selective ion channels, however no function has previously been assigned to their soluble form. Structural studies have shown that in the soluble form, CLIC proteins adopt a glutathione S-transferase (GST) fold, however, they have an active site with a conserved glutaredoxin monothiol motif, similar to the omega class GSTs. We demonstrate that CLIC proteins have glutaredoxin-like glutathione-dependent oxidoreductase enzymatic activity. CLICs 1, 2 and 4 demonstrate typical glutaredoxin-like activity using 2-hydroxyethyl disulfide as a substrate. Mutagenesis experiments identify cysteine 24 as the catalytic cysteine residue in CLIC1, which is consistent with its structure. CLIC1 was shown to reduce sodium selenite and dehydroascorbate in a glutathione-dependent manner. Previous electrophysiological studies have shown that the drugs IAA-94 and A9C specifically block CLIC channel activity. These same compounds inhibit CLIC1 oxidoreductase activity. This work for the first time assigns a functional activity to the soluble form of the CLIC proteins. Our results demonstrate that the soluble form of the CLIC proteins has an enzymatic activity that is distinct from the channel activity of their integral membrane form. This CLIC enzymatic activity may be important for protecting the intracellular environment against oxidation. It is also likely that this enzymatic activity regulates the CLIC ion channel function

Mass propagation of dendrocalamus asper by branch cutting

Dendrocalamus asperis a thick-walled bamboo species widely used for edible shoots, chop sticks, rural housing, structural and building construction, ornamental and ecotourism purposes in Malaysia. However, due to the declination of timber production, increasing human population and their ever increasing demand, natural bamboo stands will not be able to cope with the growing demand in the future. Supply of bamboo may be increased through large-scale commercial or industrial plantations to fulfil the gap between demand and supply. However, the main problem for commercial plantation of bamboo species in Malaysia is the inadequate supply of quality planting materials since most of the commercially important bamboo species do not produce or produce few seeds after long intervals. The current study was therefore, designed to investigate the mass propagation potential of D. asper through branch cutting using an easy, inexpensive and efficient method. Primary or secondary branches consisting of three to four nodes along with the swollen base were planted into plastic buckets filled with coarse sand in partial shade under nursery condition. Before planting the cuttings, bases were treated with 0, 0.2, 0.4 or 0.8% indole-3-butyric acid (exogenous IBA) solution for 5 min. The species was found to develop root, shoot and rhizome even without any rooting hormone. However, rooting ability, shoot number and length and survival percentage were significantly enhanced when cuttings were treated with IBA. Findings of the present study are expected to have significant impact on vegetative propagation of this thick-walled bamboo species

A feasibility study of low-power laser trepanning drilling of composite using modified DVD writer

In the present study, laser cutting of cotton fiber composite laminate is experimented using a modified DVD writer drive. A 250 mW diode laser is initially extracted from a DVD writer drive, and then regulated by a custom-made laser driver circuit designed using a Proteus® software. Experimental tests are carried out using multi-pass laser trepanning drilling at different drilling speeds and standoff distances (SODs). The cut quality is evaluated by measuring the extent of both oxide and resolidified resin regions. It was discovered high speed of trepanning drilling and positive SOD significantly improve cutting region quality. Furthermore, positive and negative SODs require relatively high number of passes at different drilling speeds. From SEM micrographs, it is found out that the crack formation and fiber protruding happen in thedrilling area due to thermal stresses and matrix vaporization

Bonus versus penalty: how robust are the effects of contract framing?

We study the relative effectiveness of contracts that are framed either in terms of bonuses or penalties. In one set of treatments subjects know at the time of effort provision whether they have achieved the bonus / avoided the penalty. In another set of treatments subjects only learn the success of their performance at the end of the task. We fail to observe a contract framing effect in either condition: effort provision is statistically indistinguishable under bonus and penalty contracts

Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes

<p>Abstract</p> <p>Purpose</p> <p>Hypofractionated, stereotactic body radiotherapy (SBRT) is an emerging treatment approach for prostate cancer. We present the outcomes for low-risk prostate cancer patients with a median follow-up of 5 years after SBRT.</p> <p>Method and Materials</p> <p>Between Dec. 2003 and Dec. 2005, a pooled cohort of 41 consecutive patients from Stanford, CA and Naples, FL received SBRT with CyberKnife for clinically localized, low-risk prostate cancer. Prescribed dose was 35-36.25 Gy in five fractions. No patient received hormone therapy. Kaplan-Meier biochemical progression-free survival (defined using the Phoenix method) and RTOG toxicity outcomes were assessed.</p> <p>Results</p> <p>At a median follow-up of 5 years, the biochemical progression-free survival was 93% (95% CI = 84.7% to 100%). Acute side effects resolved within 1-3 months of treatment completion. There were no grade 4 toxicities. No late grade 3 rectal toxicity occurred, and only one late grade 3 genitourinary toxicity occurred following repeated urologic instrumentation.</p> <p>Conclusion</p> <p>Five-year results of SBRT for localized prostate cancer demonstrate the efficacy and safety of shorter courses of high dose per fraction radiation delivered with SBRT technique. Ongoing clinical trials are underway to further explore this treatment approach.</p

Dynamics of Japanese encephalitis virus transmission among pigs in Northwest Bangladesh and the potential impact of pig vaccination.

BACKGROUND: Japanese encephalitis (JE) virus infection can cause severe disease in humans, resulting in death or permanent neurologic deficits among survivors. Studies indicate that the incidence of JE is high in northwestern Bangladesh. Pigs are amplifying hosts for JE virus (JEV) and a potentially important source of virus in the environment. The objectives of this study were to describe the transmission dynamics of JEV among pigs in northwestern Bangladesh and estimate the potential impact of vaccination to reduce incidence among pigs. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a comprehensive census of pigs in three JE endemic districts and tested a sample of them for evidence of previous JEV infection. We built a compartmental model to describe JEV transmission dynamics in this region and to estimate the potential impact of pig vaccination. We identified 11,364 pigs in the study area. Previous JEV infection was identified in 30% of pigs with no spatial differences in the proportion of pigs that were seropositive across the study area. We estimated that JEV infects 20% of susceptible pigs each year and the basic reproductive number among pigs was 1.2. The model suggest that vaccinating 50% of pigs each year resulted in an estimated 82% reduction in annual incidence in pigs. CONCLUSIONS/SIGNIFICANCE: The widespread distribution of historic JEV infection in pigs suggests they may play an important role in virus transmission in this area. Future studies are required to understand the contribution of pig infections to JE risk in humans and the potential impact of pig vaccination on human disease

Food environment and diabetes mellitus in South Asia: A geospatial analysis of health outcome data

BACKGROUND: The global epidemic of type 2 diabetes mellitus (T2DM) renders its prevention a major public health priority. A key risk factor of diabetes is obesity and poor diets. Food environments have been found to influence people's diets and obesity, positing they may play a role in the prevalence of diabetes. Yet, there is scant evidence on the role they may play in the context of low- and middle-income countries (LMICs). We examined the associations of food environments on T2DM among adults and its heterogeneity by income and sex. METHODS AND FINDINGS: We linked individual health outcome data of 12,167 individuals from a network of health surveillance sites (the South Asia Biobank) to the density and proximity of food outlets geolocated around their homes from environment mapping survey data collected between 2018 and 2020 in Bangladesh and Sri Lanka. Density was defined as share of food outlets within 300 m from study participant's home, and proximity was defined as having at least 1 outlet within 100 m from home. The outcome variables include fasting blood glucose level, high blood glucose, and self-reported diagnosed diabetes. Control variables included demographics, socioeconomic status (SES), health status, healthcare utilization, and physical activities. Data were analyzed in ArcMap 10.3 and STATA 15.1. A higher share of fast-food restaurants (FFR) was associated with a 9.21 mg/dl blood glucose increase (95% CI: 0.17, 18.24; p < 0.05). Having at least 1 FFR in the proximity was associated with 2.14 mg/dl blood glucose increase (CI: 0.55, 3.72; p < 0.01). A 1% increase in the share of FFR near an individual's home was associated with 8% increase in the probability of being clinically diagnosed as a diabetic (average marginal effects (AMEs): 0.08; CI: 0.02, 0.14; p < 0.05). Having at least 1 FFR near home was associated with 16% (odds ratio [OR]: 1.16; CI: 1.01, 1.33; p < 0.05) and 19% (OR: 1.19; CI: 1.03, 1.38; p < 0.05) increases in the odds of higher blood glucose levels and diagnosed diabetes, respectively. The positive association between FFR density and blood glucose level was stronger among women than men, but the association between FFR proximity and blood glucose level was stronger among men as well as among those with higher incomes. One of the study's key limitations is that we measured exposure to food environments around residency geolocation; however, participants may source their meals elsewhere. CONCLUSIONS: Our results suggest that the exposure to fast-food outlets may have a detrimental impact on the risk of T2DM, especially among females and higher-income earners. Policies should target changes in the food environments to promote better diets and prevent T2DM

A review of the genome, epidemiology, clinical features, prevention, and treatment scenario of COVID-19: Bangladesh aspects

Abstract Background The ongoing acute respiratory disease pandemic termed COVID-19 caused by a newly emerged coronavirus has jeopardized the world’s health and economic sectors. As of 20 July 2020, the virus now known as SARS-CoV-2 has already infected more than 14 million individuals and killed 612,815 patients with a mortality rate of 4.12% around the world regardless of age, gender, and race. Main body Bangladesh has become one of its worst sufferers, with 207,453 infected people and 2668 related deaths with a mortality rate of 1.29% until 20 July 2020. More than 50% of COVID-19 patients in Bangladesh are aged between 21 and 40, but elderly people aged more than 60 have the highest mortality rate (44.7%). Male individuals are also more susceptible to the virus than females and consist of 71% and 79% among the infected and deceased patients, respectively. The most prevalent clinical features following the virus incubation period are fever, fatigue, and dry cough. A phylogenetic analysis study elucidated that the virus strain found in the country has 9 single-nucleotide variants, mostly in the ORF1ab gene, and a sequence containing 3 successive variants in the N protein, which reflects a weaker strain of SARS-CoV-2, implicating a possibility of its lower mortality rate. Another investigation of 184 genome samples of SARS-CoV-2 across the country implicated a close homology with a European haplotype of SARS-CoV-2. The country has also joined the race of vaccine development and started phase III clinical trials of a candidate vaccine developed by Sinovac Research and Development Co Ltd, China. Conclusion Bangladesh, as a developing country, still struggles with the pandemic and needs to scale up its response operation and improve healthcare facilities such as testing capacity, institutional quarantine, and isolation centers and promote awareness. Preventive measures such as strict lockdown, social distancing, and boosting the existing immune system are thus considered the only contrivances. </jats:sec