Molecular phylogenetic analysis of the white-crowned forktail Enicurus leschenaulti in Borneo

Comparison of 1017 nucleotides of mitochondrial ND2 and ND3 DNA sequences of 26 individuals of white-crowned forktail Enicurus leschenaulti from SE Asia revealed multiple evolutionary lineages within Borneo. Montane birds were genetically homogeneous across localities, but diverged by more than 4.3% from all other samples. Lowland birds formed two distinct clades, one consisting of individuals from northern Borneo, and the other including individuals from western Borneo, as well as Sumatra and Malaya. Relationships among the subspecies were not well resolved. These findings indicate another example of montane and north Bornean endemicity, support the separation of the montane and lowland species, and define areas of conservation interest.     

Absence of p55 TNF Receptor Reduces Atherosclerosis,but Has No Major Effect on Angiotensin II Induced Aneurysms in LDL Receptor Deficient Mice

Background

The aim of the current study was to investigate the role of p55 TNF Receptor (p55 TNFR), the main signaling receptor for the pro-inflammatory cytokine tumor necrosis factor (TNF), in the development of two vascular disorders: atherosclerosis and angiotensin (Ang) II-induced abdominal aortic aneurysms (AAA).

Methodology/Principal Findings

p55 TNFR deficient mice were crossed to an LDL receptor deficient background and were induced for the development of either atherosclerosis or AngII-induced AAA, and compared to littermate controls, wild-type for p55 TNFR expression. p55 TNFR deficient mice developed 43% smaller atherosclerotic lesions in the aortic sinuses compared to controls. Moreover, expression of CD68, a macrophage specific marker, exhibited a 50% reduction in the aortic arches. Decreased atherosclerosis correlated with a strong down-regulation in the expression of adhesion molecules, such as VCAM-1 and ICAM-1, by p55 TNFR deficient endothelium. In addition, expression levels of the pro-inflammatory cytokines and chemokines TNF, IL-6, MCP-1 and RANTES were significantly reduced in aortas of p55 TNFR deficient mice. In contrast, in the AngII-induced model of AAA, p55 TNFR deficiency correlated with a slight trend towards increased aneurismal lethality, but the incidence of aortic rupture due to a dissecting aneurysm, and the expansion of the suprarenal aorta were not significantly different compared to controls.

Conclusion/Significance

We found that p55 TNFR expression promotes atherosclerosis, among other mechanisms, by enhancing expression of endothelial adhesion molecules, while it seems to have no major role in the development of AngII-induced AAA.     

Clinical and microbiological features of HIV-associated tuberculous meningitis in Vietnamese adults

Methods

The aim of this prospective, observational cohort study was to determine the clinical and microbiological features, outcome, and baseline variables predictive of death, in Vietnamese adults with HIV-associated tuberculous meningitis (TBM). 58 patients were admitted to the Hospital for Tropical Diseases in Ho Chi Minh City and underwent routine clinical and laboratory assessments. Treatment was with standard antituberculous therapy and adjunctive dexamethasone; antiretroviral therapy was not routinely available. Patients were followed up until the end of TB treatment or death.

Results

The median symptom duration was 11 days (range 2–90 days), 21.8% had a past history of TB, and 41.4% had severe (grade 3) TBM. The median CD4 count was 32 cells/mm³. CSF findings were as follows: median leucocyte count 438×10⁹cells/l (63% neutrophils), 69% smear positive and 87.9% culture positive. TB drug resistance rates were high (13% mono-resistance 32.6% poly-resistance 8.7% multidrug resistance). 17% patients developed further AIDS-defining illnesses. 67.2% died (median time to death 20 days). Three baseline variables were predictive of death by multivariate analysis: increased TBM grade [adjusted hazard ratio (AHR) 1.73, 95% CI 1.08–2.76, p = 0.02], lower serum sodium (AHR 0.93, 95% CI 0.89 to 0.98, p = 0.002) and decreased CSF lymphocyte percentage (AHR 0.98, 95% CI 0.97 to 0.99, p = 0.003).

Conclusions

HIV-associated TBM is devastating disease with a dismal prognosis. CSF findings included CSF neutrophil predominance, high rates of smear and culture positivity, and high rates of antituberculous drug resistance. Three baseline variables were independently associated with death: increased TBM grade; low serum sodium and decreased CSF lymphocyte percentage.     

New intrinsically radiopaque hydrophilic microspheres for embolization: synthesis and characterization

Polymeric particles currently used for embolization procedures have the disadvantage that they are radiolucent, that is, invisible on X-ray images, and consequently the interventional radiologist has to resort to angiography to (indirectly) monitor the fate of the particles. Here, we introduce intrinsically radiopaque hydrophilic microspheres. Since these microspheres can directly be visualized on X-ray images, using these microspheres for embolization purposes will allow superprecise location of the embolic material, both during and after the procedure. The microspheres, which are prepared by suspension polymerization, are based on the radiopaque monomer 2-[4-iodobenzoyl]-oxo-ethylmethacrylate and hydroxyethylmethacrylate (HEMA) and/or 1-vinyl-2-pyrrolidinone (NVP) as hydrophilic component. It has been shown that for clinically relevant X-ray visibility the spheres should contain at least 20 wt % iodine. At this iodine content, copolymerization with HEMA results in spheres that hardly imbibe water (EQ = 1.08). When HEMA is replaced by NVP, the volume swelling ratio can be significantly increased (to 1.33).     

Impaired spatial representation in CA1 after lesion of direct input from entorhinal cortex

Place-specific firing in the hippocampus is determined by path integration-based spatial representations in the grid-cell network of the medial entorhinal cortex. Output from this network is conveyed directly to CA1 of the hippocampus by projections from principal neurons in layer III, but also indirectly by axons from layer II to the dentate gyrus and CA3. The direct pathway is sufficient for spatial firing in CA1, but it is not known whether similar firing can also be supported by the input from CA3. To test this possibility, we made selective lesions in layer III of medial entorhinal cortex by local infusion of the neurotoxin gamma-acetylenic GABA. Firing fields in CA1 became larger and more dispersed after cell loss in layer III, whereas CA3 cells, which receive layer II input, still had sharp firing fields. Thus, the direct projection is necessary for precise spatial firing in the CA1 place cell population.     

The value of HDL genetics

PURPOSE OF REVIEW: To review studies on hereditary disorders of high-density lipoprotein (HDL) metabolism and studies on HDL genetics in mice, which have both provided valuable insight into the pathways of this intriguing lipoprotein and moreover revealed targets to raise HDLc to reduce atherosclerosis. RECENT FINDINGS: To date, as many as 11 genes are considered key players in the synthesis, maturation, conversion and/or catabolism of HDL. Five of these genes have been identified in humans, APOA1, LCAT, ABCA1, LIPC, and CETP, whereas the other six genes have been identified in mice, SCARB1, ABCG1, ATPB5, PLTP, LIPG and APOM. Genetic association studies are as yet the best line of evidence of the roles of the 'murine genes' in human HDL pathways. In addition to recent genetic association studies, a third section describes exciting news on six newly proposed HDL genes VNN1, GALNT2, MMAB/MVK, CTalpha, BMP-1 and SIRT1. SUMMARY: This review provides a summary of the current literature on the genetics of HDL. New information from this research area may assist us in obtaining a better understanding of HDL biology and identifying novel pharmacological targets.     

Cholera and climate: revisiting the quantitative evidence

Cholera dynamics in endemic regions display regular seasonal cycles and pronounced interannual variability. We review here the current quantitative evidence for the influence of climate on cholera dynamics with reference to the early literature on the subject. We also briefly review the incipient status of mathematical models for cholera and argue that these models are important for understanding climatic influences in the context of the population dynamics of the disease. A better understanding of disease risk related to the environment should further underscore the need for changing the socioeconomic conditions conducive to cholera.     

Specific inhibition of gene expression using a stably integrated,inducible small-interfering-RNA vector

We have designed a doxycycline-regulated form of the H1 promoter of RNA polymerase III that allows the inducible knockdown of gene expression by small interfering RNAs (siRNAs). As a proof-of-principle, we have targeted β-catenin in colorectal cancer (CRC) cells. T-cell factor (TCF) target-gene expression is induced by accumulated β-catenin, and is the main transforming event in these cells. We have shown previously that the disruption of β-catenin/TCF4 activity in CRC cells by the overexpression of dominant-negative TCF induces rapid G1 arrest and differentiation. Stable integration of our inducible siRNA vector allowed the rapid production of siRNAs on doxycycline induction, followed by specific downregulation of β-catenin. In these CRC cells, TCF reporter-gene activity was inhibited, and G1 arrest and differentiation occurred. The inhibition of two other genes using this vector system shows that it should be useful for the inducible knockdown of gene expression.