CENP-B controls centromere formation depending on the chromatin context

The centromere is a chromatin region that serves as the spindle attachment point and directs accurate inheritance of eukaryotic chromosomes during cell divisions. However, the mechanism by which the centromere assembles and stabilizes at a specific genomic region is not clear. The de novo formation of a human/mammalian artificial chromosome (HAC/MAC) with a functional centromere assembly requires the presence of alpha-satellite DNA containing binding motifs for the centromeric CENP-B protein. We demonstrate here that de novo centromere assembly on HAC/MAC is dependent on CENP-B. In contrast, centromere formation is suppressed in cells expressing CENP-B when alpha-satellite DNA was integrated into a chromosomal site. Remarkably, on those integration sites CENP-B enhances histone H3-K9 trimethylation and DNA methylation, thereby stimulating heterochromatin formation. Thus, we propose that CENP-B plays a dual role in centromere formation, ensuring de novo formation on DNA lacking a functional centromere but preventing the formation of excess centromeres on chromosomes.     

Cathepsin B increases ENaC activity leading to hypertension early in nephrotic syndrome

The NPHS2 gene, encoding the slit diaphragm protein podocin, accounts for genetic and sporadic forms of nephrotic syndrome (NS). Patients with NS often present symptoms of volume retention, such as oedema formation or hypertension. The primary dysregulation in sodium handling involves an inappropriate activation of the epithelial sodium channel, ENaC. Plasma proteases in a proteinuria‐dependent fashion have been made responsible; however, referring to the timeline of symptoms occurring and underlying mechanisms, contradictory results have been published. Characterizing the mouse model of podocyte inactivation of NPHS2 (Nphs2^?pod) with respect to volume handling and proteinuria revealed that sodium retention, hypertension and gross proteinuria appeared sequentially in a chronological order. Detailed analysis of Nphs2^?pod during early sodium retention, revealed increased expression of full‐length ENaC subunits and αENaC cleavage product with concomitant increase in ENaC activity as tested by amiloride application, and augmented collecting duct Na⁺/K⁺‐ATPase expression. Urinary proteolytic activity was increased and several proteases were identified by mass spectrometry including cathepsin B, which was found to process αENaC. Renal expression levels of precursor and active cathepsin B were increased and could be localized to glomeruli and intercalated cells. Inhibition of cathepsin B prevented hypertension. With the appearance of gross proteinuria, plasmin occurs in the urine and additional cleavage of γENaC is encountered. In conclusion, characterizing the volume handling of Nphs2^?pod revealed early sodium retention occurring independent to aberrantly filtered plasma proteases. As an underlying mechanism cathepsin B induced αENaC processing leading to augmented channel activity and hypertension was identified.     

Reduced susceptibility to eccentric exercise-induced muscle damage in resistance-trained men is not linked to resistance training-related neural adaptations

The purpose of this study was to examine the acute effects of maximal concentric vs. eccentric exercise on the isometric strength of the elbow flexor, as well as the biceps brachii muscle electromyographic (EMG) responses in resistance-trained (RT) vs. untrained (UT) men. Thirteen RT men (age: 24 ± 4 years; height: 180.2 ± 7.7 cm; body weight: 92.2 ± 16.9 kg) and twelve UT men (age: 23 ± 4 years; height: 179.2 ± 5.0 cm; body weight: 81.5 ± 8.6 kg) performed six sets of ten maximal concentric isokinetic (CON) or eccentric isokinetic (ECC) elbow flexion exercise in two separate visits. Before and after the exercise interventions, maximal voluntary contractions (MVCs) were performed for testing isometric strength. In addition, bipolar surface EMG signals were detected from the biceps brachii muscle during the strength testing. Both CON and ECC caused isometric strength to decrease, regardless of the training status. However, ECC caused greater isometric strength decline than CON did for the UT group (p = 0.006), but not for the RT group. Both EMG amplitude and mean frequency significantly decreased and increased, respectively, regardless of the training status and exercise intervention. Resistance-trained men are less susceptible to eccentric exercise-induced muscle damage, but this advantage is not likely linked to the chronic resistance training-induced neural adaptations.     

The effect of calmodulin inhibitors and the new cardiotonic drug DPI 201-106 on the formation of interprotein bonds in the cardiac troponin complex

Using the binding of labeled [125I]troponin C (TnC) to troponin I (TnI) and troponin (TnT) immobilized on a polyvinylchloride matrix, the Ca-dependent formation of interprotein bonds in the cardiac troponin complex and the effects of various drugs on the above reaction were studied. It has been found that in the absence of Ca2+ the dissociation constant, Kd, for the TnC-TnI complex in equal to (2.5 +/- 1.03).10(-7) M. In the presence of Ca2+ the number of binding sites increases twofold; the Kd value for the bonds formed thereby is (1.74 +/- 0.18).10(-7) M. The complex is stable to the effect of 5 M urea. TnC binding to immobilized TnT is nonspecific and is completely abolished by an addition of 5 M urea. DPI 201-106 used at concentrations up to 10(-3) M does not affect the Ca-dependent binding of TnC to TnI; trifluoperazine inhibits this interaction by 60%, whereas substance 48/80 inhibits the reaction by 50% when used at a concentration of 210 micrograms/ml. It is supposed that the compounds interacting with TnC affect, primarily, the cation-binding properties of troponin. These compounds can also inhibit the formation of interprotein bonds but only when used at much higher concentrations.     

The spatial diversity of bird communities in the middle taiga of the Central Siberian Plateau

The basic tendencies of territorial changes in bird communities of the middle taiga on the Central Siberian Plateau are interrelated with the differences in forestation, productivity, swampiness, bushiness, watering, and buildup of habitats and are on the whole similar to those on the West Siberian and Central Yakutsk plains, although there are also some differences. Thus, the community types of upland swamps and low-inundated meadows in combination with lowland swamps are characteristic only of West Siberia. In Central Siberia, forest ornithocomplexes are the most diverse, which is largely due to the presence of communities of woodlands and glades at different stages of overgrowing. The ecotone type of ornithocomplexes was distinguished only for Central Yakutia. In the North Urals, the formation of ornithocomplexes is significantly influenced by forestation and tree species composition but starts to be noticeably affected by altitudinal zonality as well as productivity of biocenoses and development of shrubs in habitats interrelated with this factor.     

Expression of human interferon β in mammary glands of transgenic rabbits

A biotechnological system for the production of human β-interferon was developed on the basis of a hybrid gene constructed from the coding sequence of the β interferon gene, inserted into the first exon of the sheep beta-lactoglobulin gene. It is intended for the expression of human β-interferon in mammary glands of transgenic animals. Two lines of transgenic rabbits were obtained using the hybrid gene. The tissue specificity of the expression of the transgene and the frequency of its inheritance in the first and second generations were studied. The activity of interferon was 2.2 × 10⁴ ? 7.2 × 10⁴ IU per milliliter of milk of transgenic female rabbits.     

Heart Rate Variability in Subjects with Increased Motor Activity and Athletes

Heart rate variability (HRV) was assessed with a NeiroSoft hardware and software complex in 303 subjects, including subjects with increased motor activity and athletes. Factor analysis was used to reveal the most informative HRV indices, which accounted for two-thirds of the generalized variance of the indices under study, evidencing a balanced and orderly state of the body in subjects with increased motor activity and athletes and the improvement of neurohumoral and autonomic control of motor functions.