Identification of amino acid residues critical for the B cell growth-promoting activity of HIV-1 matrix protein p17 variants

Background

HIV-1 matrix protein p17 variants (vp17s) detected in HIV-1-infected patients with non-Hodgkin's lymphoma (HIV-NHL) display, differently from the wild-type protein (refp17), B cell growth-promoting activity. Biophysical analysis revealed that vp17s are destabilized as compared to refp17, motivating us to explore structure-function relationships.

Signal-to-noise ratio of diffusion weighted magnetic resonance imaging: Estimation methods and in vivo application to spinal cord

Diffusion tensor imaging (DTI) and tractographic reconstruction may be applied for in vivo clinical spinal cord studies. However, this structure represents a challenge to current acquisition and reconstruction strategies, due to its small size, motion artifacts, partial volume effects and low signal-to-noise-ratio (SNR). Aims of this work were to select the best approach for the estimate of SNR and to use it for spinal cord diffusion weighted (DW) sequence optimization.Seven methods for the estimate of SNR were compared on uniform phantom DW images, and the best performing approach (single ROI for signal and noise, difference of images—SNR_diff) was applied for the following in vivo sequence evaluations.Fifteen sequences with different parameters (voxel size, repetition (TR) and echo (TE) times) were compared according to SNR, resolution, fractional anisotropy (FA) and tractography performances on three healthy volunteers. In vivo optimization of DW sequences resulted in: axial sequence, with voxel size = 1.5 mm × 1.5 mm × 3.5 mm, TR = 3200 ms and TE = 89 ms, sagittal sequence with voxel size = 2.2 mm × 2.2 mm × 2 mm, TR = 3000 ms and TE = 84 ms.An objective method tested on phantom and a practical index for in vivo spinal cord DTI SNR estimation allowed to obtain axial and sagittal optimized sequences, providing excellent tractographic results, with acceptable acquisition times for in vivo clinical applications.     

VEGF gene variability and type 1 diabetes: evidence for a protective role

Vascular endothelial growth factor (VEGF) is a multifunctional cytokine originally described as an angiogenic factor. A number of reports have recently demonstrated that VEGF increases pancreatic islet survival after islet transplantation by stimulating angiogenesis and improving islet revascularization. Whether VEGF can protect from the autoimmune destruction of insulin-producing beta-cells that characterizes the development of type 1 diabetes is presently unknown. To clarify this issue, we studied the association of three polymorphisms of the promoter region of VEGF with type 1 diabetes in the Italian and the Finnish populations. The polymorphisms considered [C(-2578)A, G(-1190)A, and G(-1154)A] are known to modulate in vitro and in vivo VEGF expression. We found that VEGF promoter genotypes are associated with type 1 diabetes in both populations, but with different combinations. In Italian individuals, the -2578AA and -1190AA genotypes are associated with type 1 diabetes and accelerate its onset, while in Finnish individuals, -1154GG and -1190GG protect from type 1 diabetes and delay its onset. In conclusion, because the expected functional consequence of both genotype combinations is a reduced VEGF expression in diabetic patients, we propose a protective role of VEGF in the development of type 1 diabetes.     

The three-dimensional structure of the zona pellucida in growing and atretic ovarian follicles of the mouse

Summary The present study provides further details on the fine-structural three-dimensional architecture of the zona pellucida (ZP) in growing and atretic follicles of mice by use of ruthenium red in combination with the detergents Triton X100 and saponin. These detergents were used for extraction of the soluble fraction of the zonal proteins in an attempt to expose the structural zonal glycoproteins, which in turn can be viewed as minute three-dimensional networks upon transmission- and scanning electron-microscopic examination. By use of these methods, the ZP of growing follicles appeared to be formed by interconnected filaments which also bind to globular structures building up a three-dimensional lattice. In contrast, the ZP of stage I as well as other (II and III) stages of atretic follicles showed a structure characterized by the presence of closely packed granules connected with short filaments to form a close-mesh reticulum. This structural change of the ZP, which in the present study is also associated with the disappearance of gap junctions within the granulosa and cumulus cell population, might represent one of the early events involved in the onset of atresia. These changes, most probably depending on an altered secretory activity of both oocytes and follicle cells, might lead to a degradation of the ZP network structure and to its subsequent increased density (condensation). All these morphodynamic events eventually contribute to a sequestration of the oocyte in the early stage of atresia.     

Plasmodium falciparum gametocytes: still many secrets of a hidden life

Sexual differentiation and parasite transmission are intimately linked in the life cycle of malaria parasites. The specialized cells providing this crucial link are the Plasmodium gametocytes. These are formed in the vertebrate host and are programmed to mature into gametes emerging from the erythrocytes in the midgut of a blood-feeding mosquito. The ensuing fusion into a zygote establishes parasite infection in the insect vector. Although key mechanisms of gametogenesis and fertilization are becoming progressively clear, the fundamental biology of gametocyte formation still presents open questions, some of which are specific to the human malaria parasite Plasmodium falciparum. Developmental commitment to sexual differentiation, regulation of stage-specific gene expression, the profound molecular and cellular changes accompanying gametocyte specialization, the requirement for tissue-specific sequestration in P. falciparum gametocytogenesis are proposed here as areas for future investigation. The epidemiological relevance of parasite transmission from humans to mosquito in the spread of malaria and of Plasmodium drug resistance genes indicates that understanding molecular mechanisms of gametocyte formation is highly relevant to design strategies able to interfere with the transmission of this disease.     

Studies on photosystem I. Characteristics of "310 material" isolated from spinach chloroplasts

Exposure of osmotically shocked chloroplasts to dilute pyridine and sonic oscillation results in the extraction of a small molecular-weight factor. Purification of the factor was accomplished using gel filtration chromatography. Due to the spectral nature of the purified species (λ_max at 310 nm) the factor was named “310 material.”Physiologically, the 310 material was found to inhibit a variety of ferredoxin-dependent photoreductions catalyzed by isolated spinach chloroplasts but stimulate both pseudocyclic photophosporylation and the ferredoxin-independent photoreduction of mammalian cytochrome c. The latter reaction was found to involve, at least partially, the formation of a Superoxide radical. Dark-reduction studies have further established that the 310 material is an autooxidizable electron carrier.Chemically, the 310 material is a water-soluble, low molecular-weight phenolic-type compound; possibly a derivative of coumaric acid. No proteinaceous material is observed in physiologically active preparations of 310 material.Based on these findings, it is concluded that the isolated 310 material acts on the reducing side of Photosystem I at or near the site of reduction of ferredoxin and competes with ferredoxin for the reducing power generated by the Photosystem I reaction center. The exact physiological role of the 310 material in the intact photosynthetic system, however, remains unknown.The similarities between the 310 material and a variety of other factors previously isolated from chloroplasts are discussed.     

The effects of ecolabels on environmentally- and health-friendly cars: an online survey and two experimental studies

The International Journal of Life Cycle Assessment - Given the increasing importance of political decision-making to reduce emission targets, the main purpose of the current paper is to identify...