Similar hypotensive responses to resistance exercise with and without blood flow restriction

Low intensity resistance exercise (RE) with blood flow restriction (BFR) has gained attention in the literature due to the beneficial effects on functional and morphological variables, similar to those observed during traditional RE without BFR, while the effects of BFR on post-exercise hypotension remain unclear. The aim of the present study was to compare the blood pressure (BP) response of trained normotensive individuals to RE with and without BFR. In this cross-over randomized trial, eight male subjects (23.8 ± 4 years, 74 ± 3 kg, 174 ± 4 cm) completed two exercise protocols: traditional RE (3 x 10 repetitions at 70% one-repetition maximum [1-RM]) and low intensity RE (3 x 15 repetitions at 20% 1-RM) with BFR. Blood pressure measurements were performed after 15 min of seated rest (0), immediately after and 10 min, 20 min, 30 min, 40 min, 50 min and 60 min after the experimental sessions. Similar hypotensive effects for systolic BP (SBP) were observed for both protocols (P < 0.05) after exercise, with no differences between groups (P > 0.05) and no statistically significant difference for diastolic BP (P > 0.05). These results suggest that in normotensive trained individuals, both traditional RE and RE with BFR induce hypotension for SBP, which is important to prevent cardiovascular disturbances.     

A novel nuclear trafficking module regulates the nucleocytoplasmic localization of the rabies virus interferon antagonist, p protein

Regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. Active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, NLSs) and export (nuclear export signals, NESs). Rabies virus (RabV) phospho (P) protein, which is largely responsible for antagonising the host anti-viral response, is expressed as five isoforms (P1-P5). The subcellular trafficking of these isoforms is thought to depend on a balance between the activities of a dominant N-terminal NES (N-NES) and a distinct C-terminal NLS (C-NLS). Specifically, the N-NES-containing isoforms P1 and P2 are cytoplasmic, whereas the shorter P3-P5 isoforms, which lack the N-NES, are believed to be nuclear through the activity of the C-NLS. Here, we show for the first time that RabV P contains an additional strong NLS in the N-terminal region (N-NLS), which, intriguingly, overlaps with the N-NES. This arrangement represents a novel nuclear trafficking module where the N-NLS is inactive in P1 but becomes activated in P3, concomitant with truncation of the N-NES, to become the principal targeting signal conferring nuclear accumulation. Understanding this unique switch arrangement of overlapping, co-regulated NES/NLS sequences is vital to delineating the critical role of RabV P protein in viral infection.     

Two new genera of nematode (Oxyurida,Hystrignathidae) parasites of Passalidae (Coleoptera) from the Democratic Republic of Congo

Two new genera and species parasitizing passalid beetles from the Democratic Republic of Congo are described. Kongonema meyerigen. n. sp. n. is characterized by having females with the cervical cuticle unarmed, first cephalic annule cone-like and truncate, sub-cylindrical procorpus and genital tract didelphic-amphidelphic. The males of Kongonema meyerigen. n. sp. n. have the procorpus sub-cylindrical, the dorsal cuticle of the tail end thickened, a single large, median mammiform pre-cloacal papilla and a pair of small, pre-cloacal, sub-lateral papillae at a short distance before the level of the cloaca. Lubanema decraemeraegen. n. sp. n. is characterized by the body markedly fusiform, cuticle unarmed and strongly annulated, procorpus sub-cylindrical, isthmus as a constriction between procorpus and basal bulb, genital tract monodelphic-prodelphic and the posterior end rounded with a very short tail appendage.     

Regulated nucleocytoplasmic trafficking of viral gene products: a therapeutic target?

The study of viral proteins and host cell factors that interact with them has represented an invaluable contribution to understanding of the physiology as well as associated pathology of key eukaryotic cell processes such as cell cycle regulation, signal transduction and transformation. Similarly, knowledge of nucleocytoplasmic transport is based largely on pioneering studies performed on viral proteins that enabled the first sequences responsible for the facilitated transport through the nuclear pore to be identified. The study of viral proteins has also enabled the discovery of several nucleocytoplasmic regulatory mechanisms, the best characterized being through phosphorylation. Recent delineation of the mechanisms whereby phosphorylation regulates nuclear import and export of key viral gene products encoded by important human pathogens such as human cytomegalovirus dengue virus and respiratory syncytial virus has implications for the development of antiviral therapeutics. In particular, the development of specific and effective kinase inhibitors makes the idea of blocking viral infection by inhibiting the phosphorylation-dependent regulation of viral gene product nuclear transport a real possibility. Additionally, examination of a chicken anemia virus (CAV) protein able to target selectively into the nucleus of tumor but not normal cells, as specifically regulated by phosphorylation, opens the exciting possibility of cancer cell-specific nuclear targeting. The study of nucleoplasmic transport may thus enable the development not only of new antiviral approaches, but also contribute to anti-cancer strategies.     

Using nuclear targeting signals to enhance non-viral gene transfer

Summary Gene therapy involves the introduction of DNA-encoding therapeutic gene products into appropriate cells of an affected individual. The limitations of the approach relate largely to the poor efficiency of the delivery of the therapeutic DNA to the nucleus. This review examines recent work in the area of non-viral gene transfer, building on developments in the field of nuclear protein import and their application in the field of non-viral gene transfer. In particular, advances in the area of enhancing DNA targeting to the nucleus are discussed, including the use of modular nuclear targeting signals recognised by the cellular nuclear import machinery and DNA condensing agents to facilitate passage through the nuclear pore. Optimising nuclear DNA delivery through these and other strategies should assist greatly in rendering gene therapy a viable and realistic possibility for treating disease.