A target repurposing approach identifies N-myristoyltransferase as a new candidate drug target in filarial nematodes

Myristoylation is a lipid modification involving the addition of a 14-carbon unsaturated fatty acid, myristic acid, to the N-terminal glycine of a subset of proteins, a modification that promotes their binding to cell membranes for varied biological functions. The process is catalyzed by myristoyl-CoA:protein N-myristoyltransferase (NMT), an enzyme which has been validated as a drug target in human cancers, and for infectious diseases caused by fungi, viruses and protozoan parasites. We purified Caenorhabditis elegans and Brugia malayi NMTs as active recombinant proteins and carried out kinetic analyses with their essential fatty acid donor, myristoyl-CoA and peptide substrates. Biochemical and structural analyses both revealed that the nematode enzymes are canonical NMTs, sharing a high degree of conservation with protozoan NMT enzymes. Inhibitory compounds that target NMT in protozoan species inhibited the nematode NMTs with IC50 values of 2.5-10 nM, and were active against B. malayi microfilariae and adult worms at 12.5 µM and 50 µM respectively, and C. elegans (25 µM) in culture. RNA interference and gene deletion in C. elegans further showed that NMT is essential for nematode viability. The effects observed are likely due to disruption of the function of several downstream target proteins. Potential substrates of NMT in B. malayi are predicted using bioinformatic analysis. Our genetic and chemical studies highlight the importance of myristoylation in the synthesis of functional proteins in nematodes and have shown for the first time that NMT is required for viability in parasitic nematodes. These results suggest that targeting NMT could be a valid approach for the development of chemotherapeutic agents against nematode diseases including filariasis

Effects of 8-Week Ketogenic Diet on Anthropometrics, Body Composition, Metabolic Parameters, and Psychological Factors in Young Obese Population

Obese have a significantly higher Body Mass Index (BMI), which can be associated with poor nutritional intake and sedentary lifestyles. The ketogenic diet is a form of a dietary intervention which is often implemented for metabolic syndrome individuals such as obese populations. PURPOSE: The purpose of this study was to measure the effects of a ketogenic diet on anthropometrics, body composition, metabolic parameters, and psychological factors in young obese population. METHODS: Seven young obese participants (n=7, height (cm); 174.8 ± 10.9, weight (kg); 105 ± 20.7, BMI (kg∙m-2); 34.6 ± 4.8) completed an 8-week intervention with a 70:20:10 ratio of fats to proteins to carbohydrates. Participants within the study were provided three meals per day, for a total of 8 weeks. Statistical analyses were performed with IBM Statistical Package for Social Science (SPSS 27.0, SPSS Inc., Chicago, USA). All data was reported as mean and standard deviation (SD). Dependent paired t-Test was used to determine ketogenic diet intervention effects. Frequencies were used to measure results from psychological factors. Statistical significance was set a priori p ≤ 0.05. RESULTS: Participants within the study noted significant reductions in anthropometric variables during 8 weeks: body mass (Pre: 105.8 ± 20.5 kg Post: 98.9 ± 18.8 kg, p= 0.000), BMI (Pre: 34.6 ± 4.8 kg·m-2, Post: 32.2 ± 4.2 kg·m-2, p= 0.001), waist circumference (Pre: 101.5 ± 13.9 cm, Post: 96.3 ± 13.3 cm, p= 0.000), and hip circumference (Pre: 112.6 ± 11.5 cm, Post: 107.3 ± 10.8 cm, p= 0.000). Significant reductions were shown in body composition variables: body fat (Pre: 25.6 ± 0.8%, Post: 21.1 ± 1.4%, p=0.000), and lean body mass (Post: 78.9 ± 14.9 kg, Post: 78.2 ± 14.5 kg, p=.0035). Significant reductions were shown in metabolic parameters: systolic blood pressure (Post: 126.6 ± 10.0 mmHg, Post: 120 ± 6.6 mmHg, p=0.029), diastolic blood pressure (Pre: 81.7 ± 4.9 mmHg, Post: 76.3 ± 1.8 mmHg, p= 0.020), and VO2max (Pre: 47.6 ± 8.9 mL·kg-1·min-1, Post: 51.8 ± 9.2 mL·kg-1·min-1, p=0.001. Question 1 within the psychological questionnaire results shown a reduction in the negative aspect in poor health score, with a significant increase shown towards good health. Question 3g results shown that here was a significant increase in frequencies of improvement towards having no limitations regarding walking a one-mile distance. Question 9g had significant increase in individuals selecting improved overall energy levels in comparison to baseline. CONCLUSION: The 8 weeks of ketogenic diet intervention may contribute or change bioenergetics pathways and results in significant adaptations on anthropometrics, body composition, metabolic parameters, and psychological factors in young obese population

The Effect of Covid-19 on Cardiac Health Investigated by Electrocardiogram in Collegiate Athletes

Covid-19 has emerged as a global pandemic and affected almost every organ of the body. There is limited data on cardiovascular involvement in athletes with covid-19 infection. PURPOSE: The purpose of the study is to determine the effect of covid-19 on cardiac health in collegiate athletes by electrocardiogram. METHODS: Prior to testing, all subjects signed an Informed Consent approved by the university Institutional Review Board (IRB). Screening electrocardiograms were performed in 45 Covid-19 infected basketball, football and soccer playing athletes (39 males and 6 females) of 18-25 years of age and have since shown to be negative following two successive tests. The data were then compared to ECG values in non-infected basketball, football, and soccer athletes, obtained by conducting meta-analyses with having same age and sport criteria. Descriptive statistics were means and standard deviation (SD). Additional statistical analyses utilized a Factorial ANOVA with main effect, post hoc Tukey and effect size calculations. Statistical significance is set a priori at P \u3c 0.05. RESULTS: The total number of subjects in experimental group were 12 male basketball players, 23 male football players, 4 male soccer players and 6 female Soccer players. The total number of subjects in control group obtained through meta-analyses were 591 male basketball athletes, 176 male footballers, 588 male soccer athletes and 154 female soccer athletes. The baseline characteristics of mean (SD) BMI (kg/m2) for experimental group was as follows: male basketball: 23.4 (1.77), male football: 31.5 (6.53), male soccer: 23.9 (1.55), and female soccer: 24.5 (4.52). For control groups, BMI were as follows: male basketball: 25, male football: 22.6 (7), male soccer: 23.1 (0.8), and female soccer: 21.8 (0.3). The factorial ANOVA shows that there is a significant difference in ECG parameters between male and females (p=0.001) and between sports (p= 0.000034) but not between experimental and control group (p=0.18). The post hoc Tukey analysis indicated the following: PR interval and QRS duration were significantly (p=0.006, p=0.017) higher in males compared to females, respectively; PR interval was significantly (p=0.04) lower in Soccer players compared to other sports. The resting heart rate (RHR) was significantly (p=0.01) higher in the experimental group compared to controls, yet was within normal range of heart rate. While there was not a significant difference between the two groups in the ECG parameters, there was a small to huge effect size in ECG parameters in male and female soccer players. In male soccer players between the groups, the value of Cohen D for RHR was 0.16 (very small effect size), 0.92 (large effect size) for QRS duration and 0.72 (medium effect size) for QTc interval. For the female soccer players, the value of Cohen D for RHR was 1.70 (very large effect size), and 0.67 (medium effect size) for QRS duration. There is a huge effect size in RHR in male football athletes with a Cohen D value of 2.1. CONCLUSION: The effect of Covid-19 on ECG parameters is more profound in male athletes compared to female counterparts, primarily in RHR, PR interval and QRS duration. In terms of sports, the male and female soccer players have changes in ECG parameters when compared to male football and basketball athletes

Spectrally distinct ejecta in Syrtis Major, Mars: Evidence for environmental change at the Hesperian-Amazonian boundary

Analysis of visible and near-infrared (VNIR) imaging spectrometer data of the Syrtis Major volcanic complex on Mars shows spectrally distinct ejecta (SDE) around a subset of the region's impact craters. We explore the nature of this spectral difference with the intention of constraining the physical cause of the distinction and the significance of their near random spatial distribution. Crater counting performed by Baratoux et al. (2007) indicated that the craters with SDE are systematically younger than craters without SDE. Extensive crater counts of the craters with SDE show that they fit a consistent Hartmann (2005) isochron indicting that they represent temporally continuous population. This population was dated near 2 Ga, consistent with the counts of Baratoux et al. (2007). This modeled age corresponds to just after the Hesperian-Amazonian boundary, indicating that it may be related to a global event. We explore possible explanations for the lack of SDE around older craters, including atmospheric changes, significant but brief regional emplacement of materials, and volcanic activity. We conclude that the preferred explanation is that the SDE represent the true composition of the Syrtis Major volcanics and that surfaces older than 2 Ga were altered by interactions with water vapor or volcanic gases under different Hesperian climatic and atmospheric conditions leading to all craters formed after this alteration event to display SDE

The Relationship Between Landing Mechanics and Injury Risk in Women\u27s Collegiate Soccer Players

Mechanical performance in landing related tasks has been suggested to be related to injury in athletic. PURPOSE: The purpose of this investigations was to assess relationships which may exist between performance in landing mechanics and injury rates throughout a women’s NCAA Division II Collegiate Soccer season. METHODS: Twenty-eight women (age 19.7±1.6 yrs, height 1.6±0.5 m, mass 63.4±7.9 kg) were assessed using the Landing Error Scoring System (LESS) test prior to a competitive season. Injury rates, types, and time lost from participation were tracked throughout the season. Injury information was coded and categorized each week in the following: acute vs. chronic; soft vs. hard tissue; upper vs. lower body; specific anatomical location; contact vs. non-contact; week of injury occurrence; practice days missed from injury; and games missed from injury. Association was measured via a Spearman\u27s rank correlation coefficient and a stepwise linear regression was performed for any variables which showed significant correlation to determine predictive relationships which may exist. The LESS test was evaluated independently by multiple raters and inter-rater reliability was high (ICC=0.824, 95% CI upper and lower = 0.917-0.657, p=0.001). Statistical significance was set a priori at p≤0.05. RESULTS: No significant correlations were determined between LESS test performance and injury and the LESS score did not add strength of association to any predictive variables. DISCUSSION: The main finding of this investigation is that performance on the LESS test did not show significant association with injury rates in women’s collegiate soccer players. LESS test performance has previously been suggested to be a valid and reliable clinical assessment tool, and claims have been made regarding its utility as a screening tool for identification of persons who may be at risk for subsequent injury. Landing mechanics may still be a valid predictor of injury risk. However, the results of our investigation do not support the use of the LESS test as a screening tool for injury risk in women’s collegiate soccer athletes

Kondo effect in quantum dots

We review mechanisms of low-temperature electronic transport through a quantum dot weakly coupled to two conducting leads. Transport in this case is dominated by electron-electron interaction. At temperatures moderately lower than the charging energy of the dot, the linear conductance is suppressed by the Coulomb blockade. Upon further lowering of the temperature, however, the conductance may start to increase again due to the Kondo effect. We concentrate on lateral quantum dot systems and discuss the conductance in a broad temperature range, which includes the Kondo regime