Differences in neuromuscular control between impact and no impact roundhouse kick in athletes of different skill levels

This study aimed at investigating two aspects of neuromuscular control around the hip and knee joint while executing the roundhouse kick (RK) using two techniques: Impact RK (IRK) at trunk level and No-Impact RK at face level (NIRK). The influence of technical skill level was also investigated by comparing two groups: elite Karateka and Amateurs. Surface electromyographic (sEMG) signals have been recorded from the Vastus Lateralis (VL), Biceps Femoris (BF), Rectus Femoris (RF), Gluteus Maximum (GM) and Gastrocnemious (GA) muscles of the kicking leg in six Karateka and six Amateurs performing the RKs. Hip and knee kinematics were also assessed. EMG data were rectified, filtered and normalized to the maximal value obtained for each muscle over all trials; co-activation (CI) indexes of antagonist vs. overall (agonist and antagonist) activity were computed for hip and knee flexion and extension. Muscle Fiber Conduction Velocity (CV) obtained from VL and BF muscles was assessed as well. The effect of group and kick on angular velocity, CIs, and CVs was tested through a two-way ANOVA (p < 0.05). An effect of group was showed in both kicks. Karateka presented higher knee and hip angular velocity; higher BF-CV (IRK: 5.1 ± 1.0 vs. 3.5 ± 0.5 m/s; NIRK: 5.7 ± 1.3 vs. 4.1 ± 0.5 m/s), higher CIs for hip movements and knee flexion and lower CI for knee extension. The results obtained suggest the presence of a skill-dependent activation strategy in the execution of the two kicks. CV results are suggestive of an improved ability of elite Karateka to recruit fast MUs as a part of training induced neuromuscular adaptation.     

Strategies for the highly efficient synthesis of erythropoietin N‐glycopeptide hydrazides

A convergent synthesis for erythropoietin (EPO) 1‐28 N‐glycopeptide hydrazides was developed. In this approach, EPO 1‐28 peptides were synthesized on the solid phase and converted to C‐terminal hydrazides after cleavage from the resin. After selective deprotection of the Asp24 side chain, the desired glycosylamine was coupled by pseudoproline‐assisted Lansbury aspartylation. Although the initial yields of the EPO 1‐28 glycopeptides were satisfactory, they could be markedly improved by increasing the purity of the peptide using a reversed‐phase high‐performance liquid chromatography (RP‐HPLC) purification of the protected peptide.     

High resolution TOF MS coupled to CE for the analysis of isotopically resolved intact proteins

Intact protein analysis by mass spectrometry is of great interest for the characterisation of biotechnological products. Exact mass measurement in combination with isotopic resolution allows the detection of modifications leading to small mass changes like deamidation or reduction of disulfide bonds directly on the level of the intact protein. Here, a concept is presented based on time-of-flight mass spectrometry. A bench top TOF MS and a high resolution TOF MS were used to resolve the isotopes of intact recombinant human growth hormone and intact human erythropoietin, respectively. Thus, these 22 and around 30kDa large proteins can be characterised sensitively in great detail and along with capillary electrophoretic separation unambiguous identification of minor protein modifications like deamidation is possible.     

Overexpression of Arabidopsis cytokinin oxidase/dehydrogenase genes AtCKX1 and AtCKX2 in transgenic Centaurium erythraea Rafn.

Cytokinin oxidase/dehydrogenase (CKX) is the only known enzyme involved in cytokinin catabolism. Genes coding for two Arabidopsis CKX isoforms, AtCKX1 and AtCKX2, were introduced separately into a binary cloning vector, immobilized into Agrobacterium tumefaciens strain GV3101, and introduced into root explants of centaury (Centaurium erythraea Rafn.). The integration of each transgene was confirmed by genomic PCR. Of the total transformed explants, 30 and 28.2 % of the transformants carried AtCKX1 and AtCKX2 transgenes, respectively. Of these transformants, 50 % exhibited expression of the AtCKX1 transgene, while 64 % of transformants exhibited expression of the AtCKX2 transgene. For all analysed AtCKX transgenic centaury lines, as well as for untransformed control plants, CKX activity was higher in roots than in shoots. Expression of AtCKX in most transgenic lines contributed to enhanced levels of CKX activity in root tissues; whereas, only a few lines demonstrated increased CKX activity in shoot tissues compared to those of control plants. Moreover, overexpression of AtCKX resulted in reduced morphogenetic potential in transgenic plants, but did not significantly affect biomass production in comparison to untransformed control plants.     

Similarities and differences for membranotropic action of three unnatural antimicrobial peptides

Previously, we described the design and synthesis of three nine‐residue AMPs, P9Nal(SS), P9Trp(SS), and P9Nal(SR), showing high stability in serum and broad spectrum antimicrobial activity. The peptides P9Trp(SS) and P9Nal(SR) differ from P9Nal(SS) for the replacement of the two 2Nal residues with Trp residues and for the replacement of the two Cys (StBu) with Cys (tBu) residues, respectively. These changes led to peptides with a lower hydrophobicity respect to the P9Nal(SS). Interestingly, the three peptides have very similar activity against Gram‐negative bacteria. Instead, they exhibit a significant difference towards Gram‐positive bacteria, being P9Nal(SS) the most active. In order to evaluate the impact of amino acids substitution on membranotropic activity and rationalize the observed effects in vivo, here, we report the detailed biophysical characterization of the interaction between P9Nal(SR) and P9Trp(SS) and liposomes by combining differential scanning calorimetry, circular dichroism, and fluorescence spectroscopy. The comparison with the results for the previously characterized P9Nal(SS) peptide reveals similarities and differences on the interaction process and perturbation activities. It was found that the three peptides can penetrate at different extent inside the bilayer upon changing their conformation and inducing lipid domains formation, revealing that the formation of lipid domains is fundamental for the activity against Gram‐negative bacteria. On the contrary, the dissimilar activity against Gram‐positive bacteria well correlate with the different affinity of peptides for the lipoteichoic acid, a component selectively present in the cell wall of Gram‐positive bacteria.     

microRNA-122 Dependent Binding of Ago2 Protein to Hepatitis C Virus RNA Is Associated with Enhanced RNA Stability and Translation Stimulation

Translation of Hepatitis C Virus (HCV) RNA is directed by an internal ribosome entry site (IRES) in the 5′-untranslated region (5′-UTR). HCV translation is stimulated by the liver-specific microRNA-122 (miR-122) that binds to two binding sites between the stem-loops I and II near the 5′-end of the 5′-UTR. Here, we show that Argonaute (Ago) 2 protein binds to the HCV 5′-UTR in a miR-122-dependent manner, whereas the HCV 3′-UTR does not bind Ago2. miR-122 also recruits Ago1 to the HCV 5’-UTR. Only miRNA duplex precursors of the correct length stimulate HCV translation, indicating that the duplex miR-122 precursors are unwound by a complex that measures their length. Insertions in the 5′-UTR between the miR-122 binding sites and the IRES only slightly decrease translation stimulation by miR-122. In contrast, partially masking the miR-122 binding sites in a stem-loop structure impairs Ago2 binding and translation stimulation by miR-122. In an RNA decay assay, also miR-122-mediated RNA stability contributes to HCV translation stimulation. These results suggest that Ago2 protein is directly involved in loading miR-122 to the HCV RNA and mediating RNA stability and translation stimulation.     

An Epidemiologic Investigation of Potential Risk Factors for Nodding Syndrome in Kitgum District,Uganda

Introduction

Nodding Syndrome (NS), an unexplained illness characterized by spells of head bobbing, has been reported in Sudan and Tanzania, perhaps as early as 1962. Hypothesized causes include sorghum consumption, measles, and onchocerciasis infection. In 2009, a couple thousand cases were reportedly in Northern Uganda.

Methods

In December 2009, we identified cases in Kitgum District. The case definition included persons who were previously developmentally normal who had nodding. Cases, further defined as 5- to 15-years-old with an additional neurological deficit, were matched to village controls to assess risk factors and test biological specimens. Logistic regression models were used to evaluate associations.

Results

Surveillance identified 224 cases; most (95%) were 5–15-years-old (range = 2–27). Cases were reported in Uganda since 1997. The overall prevalence was 12 cases per 1,000 (range by parish = 0·6–46). The case-control investigation (n = 49 case/village control pairs) showed no association between NS and previously reported measles; sorghum was consumed by most subjects. Positive onchocerciasis serology [age-adjusted odds ratio (AOR₁) = 14·4 (2·7, 78·3)], exposure to munitions [AOR₁ = 13·9 (1·4, 135·3)], and consumption of crushed roots [AOR₁ = 5·4 (1·3, 22·1)] were more likely in cases. Vitamin B6 deficiency was present in the majority of cases (84%) and controls (75%).

Conclusion

NS appears to be increasing in Uganda since 2000 with 2009 parish prevalence as high as 46 cases per 1,000 5- to 15-year old children. Our results found no supporting evidence for many proposed NS risk factors, revealed association with onchocerciasis, which for the first time was examined with serologic testing, and raised nutritional deficiencies and toxic exposures as possible etiologies.     

Association of Soluble Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) with Central Adiposity and Low-Density Lipoprotein Cholesterol

Objective

Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL), in addition to having a prognostic value in patients with cardiovascular disease, seems to interact with adiposity, insulin resistance and other cardiovascular risk factors. However, the results of previous clinical studies, focused on the association of TRAIL with selected metabolic or anthropometric indices were inconclusive. The aim of this study was to further investigate how soluble TRAIL concentrations independently correlate with major cardiovascular risk factors, including lipid, glycemic and anthropometric features.

Materials/Methods

We examined the associations between serum soluble TRAIL concentrations, measured by ELISA, and lipid, glycemic and anthropometric features in 199 subjects recruited at our Metabolic Outpatient Clinic.

Results

Soluble TRAIL concentrations had a significant and direct correlation with total cholesterol (p = 0.046), LDL-cholesterol (p = 0.032), triglycerides (p = 0.01), body mass index (p = 0.046), waist circumference (p = 0.008), fat mass (p = 0.056) and insulin (p = 0.046) and an inverse correlation with HDL-cholesterol (p = 0.02). In multivariable regression analyses adjusted for potential confounders (age, gender, C-reactive protein, HDL-cholesterol, triglycerides, waist circumference, and insulin), TRAIL levels continued to have an independent correlation with LDL-cholesterol and waist circumference (r² = 0.04).

Conclusions

Serum TRAIL levels were weakly but significantly and independently associated with waist circumference, a marker of visceral adiposity, and with LDL-cholesterol. Further studies are needed to clarify the biological basis of these relationships.     

Personality,Metabolic Rate and Aerobic Capacity

Personality traits and cardiorespiratory fitness in older adults are reliable predictors of health and longevity. We examined the association between personality traits and energy expenditure at rest (basal metabolic rate) and during normal and maximal sustained walking. Personality traits and oxygen (VO₂) consumption were assessed in 642 participants from the Baltimore Longitudinal Study of Aging. Results indicate that personality traits were mostly unrelated to resting metabolic rate and energy expenditure at normal walking pace. However, those who scored lower on neuroticism (r =  −0.12) and higher on extraversion (r = 0.11), openness (r = 0.13), and conscientiousness (r = 0.09) had significantly higher energy expenditure at peak walking pace. In addition to greater aerobic capacity, individuals with a more resilient personality profile walked faster and were more efficient in that they required less energy per meter walked. The associations between personality and energy expenditure were not moderated by age or sex, but were in part explained by the proportion of fat mass. In conclusion, differences in personality may matter the most during more challenging activities that require cardiorespiratory fitness. These findings suggest potential pathways that link personality to health outcomes, such as obesity and longevity.     

Identification of GNE-293, a potent and selective PI3Kδ inhibitor: Navigating in vitro genotoxicity while improving potency and selectivity

In an effort to identify potent and isoform selective inhibitors of PI3Kδ, GNE-293 (34) was identified. Inhibitor 2 was found to induce micronuclei formation in both the MNT and HCA in vitro assays. Compounds testing negative for genotoxicity were successfully identified through modifications of the 2-benzimidazole substituent and the methylene moiety to disrupt planarity. A variety of heteroatom linkers were explored to examine their effect on potency and isoform selectivity by restricting torsional angles to favor ligand interactions with PI3Kδ’s Trp760. These modifications also resulted in an improved in vivo pharmacokinetic profile.