The B30.2(SPRY) domain of the retroviral restriction factor TRIM5alpha exhibits lineage-specific length and sequence variation in primates

Tripartite motif (TRIM) proteins are composed of RING, B-box 2, and coiled coil domains. Some TRIM proteins, such as TRIM5alpha, also possess a carboxy-terminal B30.2(SPRY) domain and localize to cytoplasmic bodies. TRIM5alpha has recently been shown to mediate innate intracellular resistance to retroviruses, an activity dependent on the integrity of the B30.2 domain, in particular primate species. An examination of the sequences of several TRIM proteins related to TRIM5 revealed the existence of four variable regions (v1, v2, v3, and v4) in the B30.2 domain. Species-specific variation in TRIM5alpha was analyzed by amplifying, cloning, and sequencing nonhuman primate TRIM5 orthologs. Lineage-specific expansion and sequential duplication occurred in the TRIM5alpha B30.2 v1 region in Old World primates and in v3 in New World monkeys. We observed substitution patterns indicative of selection bordering these particular B30.2 domain variable elements. These results suggest that occasional, complex changes were incorporated into the TRIM5alpha B30.2 domain at discrete time points during the evolution of primates. Some of these time points correspond to periods during which primates were exposed to retroviral infections, based on the appearance of particular endogenous retroviruses in primate genomes. The results are consistent with a role for TRIM5alpha in innate immunity against retroviruses.     

Socio-economic inequity in demand for insecticide-treated nets, in-door residual house spraying, larviciding and fogging in Sudan

Background

Malaria continues to claim one to two million lives a year, mainly those of children in sub-Saharan Africa. Reduction in mortality depends, in part, on improving the quality of hospital care, the training of healthcare workers and improvements in public health. This study examined the prognostic indicators of severe falciparum malaria in Gabonese children.

Methods

An observational study examining the clinical presentations and laboratory features of severe malaria was conducted at the Centre Hospitalier de Libreville, Gabon over two years. Febrile children aged from 0 to 10 years with Plasmodium falciparum infection and one or more features of severe malaria were enrolled.

Results

Most children presenting with severe falciparum malaria were less than 5 years (92.3% of 583 cases). Anaemia was the most frequent feature of severe malaria (67.8% of cases), followed by respiratory distress (31%), cerebral malaria (24%) hyperlactataemia (16%) and then hypoglycaemia (10%). Anaemia was more common in children under 18 months old, while cerebral malaria usually occurred in those over 18 months. The overall case fatality rate was 9%. The prognostic indicators with the highest case fatality rates were coma/seizures, hyperlactataemia and hypoglycaemia, and the highest case fatality rate was in children with all three of these features.

Conclusions

Prompt and appropriate, classification and treatment of malaria helps identify the most severely ill children and aids early and appropriate management of the severely ill child.     

Human recent thymic emigrants--identification, expansion, and survival characteristics

This study shows that, in humans at birth, circulating T cells represent recent thymic emigrants (RTEs) as reflected in their high level of expression of TCR excision circles. RTEs express "thymocyte-like" characteristics with regard to rapid rate of apoptosis. In the presence of common gamma-chain cytokines, in particular IL-7, they show enhanced potential to survive, entry into cell cycle, and proliferation. Although common gamma-chain cytokines were also potent antiapoptotic stimuli for mature adult-derived naive CD4+CD45RA+ T cells, these cells were refractory to IL-7-induced expansion in vitro. RTEs cultured with IL-7 could not reinduce recombination-activating gene-2 gene expression in vitro. These data suggest that postthymic naive T cells in the periphery during early life are at a unique stage in ontogeny as RTEs, during which they can undergo homeostatic regulation including expansion and survival in an Ag-independent manner while maintaining their preselected TCR repertoire.     

Acylated flavonol glycosides from Eugenia jambolana leaves.

Two acylated flavonol glycosides and 15 known polyphenols have been isolated and identified from the leaves of Eugenca jambolana Lam. The structures of the new compounds were identified as 3-O-(4"-O-acetyl)-alpha-L-rhamnopyranoside of mearnsetin (myricetin 4'-methyl ether) and myricetin 3-O-(4"-O-acetyl-2"-O-galloyl)-alpha-L-rhamnopyranoside. The complete structure elucidation of all isolated metabolites based on chemical and spectroscopic methods of analysis (UV, 1D and 2D NMR) as well as negative ESI-MS with and without CID in-source fragmentation.     

Pregnene derivatives from Solenostemma argel leaves

Two new pregnene derivatives 14beta-15alpha-dihydroxy-delta4pregnene-3,20 dione and 3beta-14beta,15alpha-16alpha hydroxy-20-oxo-delta5pregnene-tetra-ol, in addition to alpha- and beta-amyrin and beta-sitosterol, were isolated from Solenostemma argel leaves. The structures were established by extensive spectral analysis as well as comparison with reference materials.     

Transgenics,uncertainty and public credibility

Transgenic Research -     

Biomedical applications of fluorescence imaging in vivo

Optical imaging can advance knowledge of cellular biology and disease at the molecular level in vitro and, more recently, in vivo. In vivo optical imaging has enabled real-time study to track cell movement, cell growth, and even some cell functions. Thus, it can be used in intact animals for disease detection, screening, diagnosis, drug development, and treatment evaluation. This review includes a brief introduction to fluorescence imaging, fluorescent probes, imaging devices, and in vivo applications in animal models. It also describes a quantitative fluorescence detection method with a reconstruction algorithm for determining the location of fluorophores in tissue and addresses future applications of in vivo fluorescence imaging.     

Neurophysiologic detector-a selective and sensitive tool in high-performance liquid chromatography

In the present study neurons from the olfactory system of the fish crucian carp, Carassius carassius L. were used as components in an in-line neurophysiologic detector (NPD) to measure physiological activities following the separation of substances by high-performance liquid chromatography (HPLC). The skin of crucian carp, C. carassius L. contains pheromones that induce an alarm reaction in conspecifics. Extra-cellular recordings were made from neurons situated in the posterior part of the medial region of the olfactory bulb known to mediate this alarm reaction. The nervous activity of these specific neurons in the olfactory bulb of crucian carp was used as an in-line neurophysiologic detector. HPLC was performed with an HP 1100 model equipped with a diode array detector (DAD) and ChemStation software. An adsorbosphere nucleotide-nucleoside 7 microm column was used to separate the substances in the skin extract using artificial pound water (APW) as the mobile phase. UV spectral detection was performed at 214, 254 and 345 nm, and scans (190-400 nm) were collected continuously. This system enabled the selection of peaks in the chromatogram with fish alarm pheromone activity. The neurons in parts of the olfactory system from different aquatic organisms and vertebrates can be used for the detection of species-specific stimuli such as sexual and alarm signals, food odours, and other physiologically significant substances. NPDs clearly offer new and promising options for in-line HPLC as highly selective and sensitive detectors in biological, medical and pharmaceutical research.     

Normal coordinate analyses of 3,5-dichlorophenylcyanamide

The structure of 3,5-dichlorophenylcyanamide c-C₆H₃Cl₂–NHCN was investigated by DFT-B3LYP and ab initio MP2 calculations with the 6-311+G** basis set. The planar to perpendicular rotational barrier was calculated to be of about 5 kcal mol^–1 at both levels of calculation. The stability of the planar structure of the molecule was explained on the basis of conjugation effects between the cyanamide–NHCN moiety and the phenyl c-C₆H₅ ring in agreement with earlier NMR results. The CNC and the HNC bond angles were calculated to be about 120° especially by MP2 calculation, which is consistent with sp² (planar –NH–CN group) and not sp³ (pyramidal –NH–CN group) structure. The vibrational frequencies of the d₀, d₁ and d₃ species of 3,5-dichlorophenylcyanamide and the potential energy distributions among symmetry coordinates of the normal modes of the parent molecule were computed at the DFT-B3LYP level. The calculated infrared and Raman spectra of the molecule were plotted. Complete vibrational assignments were made on the basis of isotopic substitution and normal coordinate calculations.Figure Potential curves for the internal rotation in 3,5-dichlorophenylcyanamide as determined by DFT-B3LYP/6-311+G** (solid) and MP2/6-311+G** (dotted) calculations