Antilocalization of hole carriers in Pb(1-x)Eu(x)Te alloys in the metallic regime

Magnetoresistance measurements in p-type Pb(1-x)Eu(x)Te alloys, for x varying from 0% up to 5%, have been used to investigate localization and antilocalization effects. These are attributed to both the spin-orbit scattering and to the large Zeeman splitting present in these alloys due to the large values of the effective Lande g factor. The magnetoresistance curves are analyzed using the model of Fukuyama and Hoshino, which takes into account the spin-orbit and Zeeman scattering mechanisms. The spin-orbit scattering time is found to be independent of the temperature, while the inelastic-scattering time increases with decreasing temperature suggesting the electron-phonon interaction as the main scattering mechanism.

Development of nitrosyl ruthenium complex-loaded lipid carriers for topical administration: improvement in skin stability and in nitric oxide release by visible light irradiation

The prominent nitric oxide (NO) donor [Ru(terpy)(bdqi)NO](PF(6))(3) has been synthesized and evaluated with respect to noteworthy biological effects due to its NO photorelease, including vascular relaxation and melanoma cell culture toxicity. The potential for delivering NO in therapeutic quantities is tenable since the nitrosyl ruthenium complex (NRC) must first reach the ""target tissue"" and then release the NO upon stimulus. In this context. NRC-loaded lipid carriers were developed and characterized to further explore its topical administration for applications such as skin cancer treatment. NRC-loaded solid lipid nanoparticles (SLN) and nanostructured lipid carriers were prepared via the microemulsification method, with average diameters of 275 +/- 15 nm and 211 +/- 31 nm and zeta potentials of -40.7 +/- 10.4 mV and -50.0 +/- 7.5 mV, respectively. In vitro kinetic studies of NRC release from nanoparticles showed sustained release of NRC from the lipid carriers and illustrated the influence of the release medium and the lyophilization process. Stability studies showed that NO is released from NRC as a function of temperature and time and due to skin contact. The encapsulation of NRC in SLN followed by its lyophilization, significantly improved the complex stability. Furthermore, of particular interest was the fact that in the NO photorelease study, the NO release from the NRC-loaded SLN was approximately twice that of just NRC in solution. NRC-loaded SLN performs well enough at releasing and protecting NO degradation in vitro that it is a promising carrier for topical delivery of NO. (C) 2010 Elsevier B.V. All rights reserved.

Sustained release carriers used to delivery bone morphogenetic proteins in the bone healing process

Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the transforming growth factor beta superfamily, especially BMP-2, induce bone formation in vivo, and clinical application in repair of bone fractures and defects is expected. However, appropriate systems to delivery BMPs for practical use need to be developed with the objective to heal cartilage and bone-related diseases in medical, dental and veterinary practice. Thus, the aim of this article was to present an overview of the principals carriers used to delivery BMPs and alternative delivery systems for these proteins.

Virus or not? Phylogenetics of polydnaviruses and their wasp carriers

Our current, still limited, understanding of the comparative biology and evolution of polydnaviruses (PDVs) is reviewed, especially in the context of the possible origins of these parasitoid viruses and of their coevolution with carrier wasps. A hypothetical scenario of evolution of PDVs from ascovirus (or ascovirus-like) ancestors is presented, with examples of apparent extant transitional forms. PDVs appear, in the case of bracoviruses, to show phylogenetic relationships that mirror those of their wasp carriers: with ichno-viruses, the picture is less clear. Ongoing sequencing studies of entire PDV genomes from diverse wasp species are likely to greatly contribute to our understanding of PDV evolution. (C) 2003 Elsevier Science Ltd. All rights reserved.

Superior discriminating value of ACTH-stimulated serum 21-deoxycortisol in identifying heterozygote carriers for 21-hydroxylase deficiency

P>Background Congenital adrenal hyperplasia caused by classic 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder with a high prevalence of asymptomatic heterozygote carriers (HTZ) in the general population, making case detection desirable by routine methodology. HTZ for classic and nonclassic (NC) forms have basal and ACTH-stimulated values of 17-hydroxyprogesterone (17OHP) that fail to discriminate them from the general population. 21-Deoxycortisol (21DF), an 11-hydroxylated derivative of 17OHP, is an alternative approach to identify 21OHD HTZ. Objective To determine the discriminating value of basal and ACTH-stimulated serum levels of 21DF in comparison with 17OHP in a population of HTZ for 21OHD (n = 60), as well as in NC patients (n = 16) and in genotypically normal control subjects (CS, n = 30), using fourth generation tandem mass spectrometry after HPLC separation (LC-MS/MS). Results Basal 21DF levels were not different between HTZ and CS, but stimulated values were increased in the former and virtually nonresponsive in CS. Only 17 center dot 7% of the ACTH-stimulated 21DF levels overlapped with CS, when compared to 46 center dot 8% for 17OHP. For 100% specificity, the sensitivities achieved for ACTH-stimulated 21DF, 17OHP and the quotient [(21DF + 17OHP)/F] were 82 center dot 3%, 53 center dot 2% and 87%, using cut-offs of 40, 300 ng/dl and 46 (unitless), respectively. Similar to 17OHP, ACTH-stimulated 21DF levels did not overlap between HTZ and NC patients. A positive and highly significant correlation (r = 0 center dot 846; P < 0 center dot 001) was observed between 21DF and 17OHP pairs of values from NC and HTZ. Conclusion This study confirms the superiority of ACTH-stimulated 21DF, when compared to 17OHP, both measured by LC-MS/MS, in identifying carriers for 21OHD. Serum 21DF is a useful tool in genetic counselling to screen carriers among relatives in families with affected subjects, giving support to molecular results.

Increased Levels of Circulating Endothelial Progenitor Cells in Human T-cell Lymphotropic Virus Type I Carriers

Background and Aims. HTLV-I-transformed T cells secrete biologically active forms of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF). In addition, HTLV-I-transformed cells have a high capacity of adhesion to endothelial cells. Methods. We measured the circulating endothelial progenitor cells (EPCs) and mature endothelial cells (MECs) by flow cytometry in 27 HTLV-I carriers in comparison to 30 healthy, age- and gender-matched subjects. All subjects had HTLV-I positivity confirmed by Western blot and/or polymerase chain reaction (PCR). The numbers of different subpopulations of EPCs and MECSs were evaluated by four-color flow cytometry using a panel of monoclonal antibodies. All reactions were done in duplicate to confirm reproducibility of the results. Results. The median age of all 27 HTLV-I carriers enrolled in this study was 45 years (range: 27-65 years); 11(41%) were male and 16 (59%) were female. The median age of the 30 healthy subjects in the control group was 45.5 years (range: 20-63 years); 11 (36.6%) were male and 19 (63.4%) were female. The number of EPCs was significantly higher in HTLV-I carriers (median 0.8288 cells/mu L, range: 0.0920-3.3176 cells/mu L) as compared to control group (median 0.4905 cells/mu L, range: 0.0000-1.5660 cells/mu L) (p = 0.035). In contrast, the median of the MECs in the HTLV-I carriers was 0.6380 cells/mu L (range: 0.0473-5.7618 cells/mu L) and 0.4950 cells/mu L (range: 0.0000-4.0896 cells/mu L) in the control group, with no statistical difference (p = 0.697). Conclusions. We demonstrated that EPCs, but not MECs, are increased in the peripheral blood of HTLV-I carriers. (C) 2011 IMSS. Published by Elsevier Inc.

Clinical and biochemical studies in mucopolysaccharidosis type II carriers

The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16-57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for non-carriers; there was, however, an overlap between carriers` and non-carriers` values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations.

Detection of Spinal Muscular Atrophy Carriers in a Sample of the Brazilian Population

Background: Spinal muscular atrophy is a common autosomal recessive neuromuscular disorder caused by mutations in the SMN1 gene. Identification of spinal muscular atrophy carriers has important implications for individuals with a family history of the disorder and for genetic counseling. The aim of this study was to determine the frequency of carriers in a sample of the nonconsanguineous Brazilian population by denaturing high-performance liquid chromatography (DHPLC). Methods: To validate the method, we initially determined the relative quantification of DHPLC in 28 affected patients (DHPLC values: 0.00) and 65 parents (DHPLC values: 0.49-0.69). Following quantification, we studied 150 unrelated nonconsanguineous healthy individuals from the general population. Results: Four of the 150 healthy individuals tested (with no family history of a neuromuscular disorder) presented a DHPLC value in the range of heterozygous carriers (0.6-0.68). Conclusions: Based on these results, we estimated there is a carrier frequency of 2.7% in the nonconsanguineous Brazilian population, which is very similar to other areas of the world where consanguineous marriage is not common. This should be considered in the process of genetic counseling and risk calculations. Copyright (C) 2011 S. Karger AG, Basel

Osteoinductivity potential of rhBMP-2 associated with two carriers in different dosages

The objective of this study was to evaluate bone formation after application of different doses of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with monoolein or poloxamer gels, in critical bone defects of rats. Forty-five Wistar rats were divided into nine treatment groups with five animals each: I: application of 1 A mu g rhBMP-2 + monoolein; II: 3 A mu g rhBMP-2 + monoolein; III: 7 A mu g rhBMP-2 + monoolein; IV: 1 A mu g rhBMP-2 + poloxamer; V: 3 A mu g rhBMP-2 + poloxamer; VI: 7 A mu g rhBMP-2 + poloxamer; VII: monoolein only; VIII: poloxamer only; and IX: critical bone defect only. A critical-sized defect of 6 mm diameter was produced in the left parietal bone and it was filled with gels of the above mentioned treatments. After 2 weeks, the calvarial bones were removed for histological processing. Bone formation in the groups that received poloxamer gel and rhBMP-2 was not significantly different from the control group (IX). Groups receiving monoolein and rhBMP-2 (1 and 3 A mu g) and those that received only the carriers (VII and VIII) had less bone formation in relation to the control. The association of rhBMP-2 to both poloxamer and monoolein did not exhibit any significant differentiation in bone formation in comparison with the control group.

A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers

RAD51 colocalizes with both BRCA1 and BRCA2, and genetic variants in RAD51 would be candidate BRCA1/2 modifiers. We searched for RAD51 polymorphisms by sequencing 20 individuals. We compared the polymorphism allele frequencies between female BRCA1/2 mutation carriers with and without breast or ovarian cancer and between population-based ovarian cancer cases with BRCA1/2 mutations to cases and controls without mutations. We discovered two single nucleotide polymorphisms (SNPs) at positions 135 g-->c and 172 g-->t of the 5' untranslated region. In an initial group of BRCA1/2 mutation carriers, 14 (21%) of 67 breast cancer cases carried a c allele at RAD51:135 g-->c, whereas 8 (7%) of 119 women without breast cancer carried this allele. In a second set of 466 mutation carriers from three centers, the association of RAD51:135 g-->c with breast cancer risk was not confirmed. Analyses restricted to the 216 BRCA2 mutation carriers, however, showed a statistically significant association of the 135 c allele with the risk of breast cancer (adjusted odds ratio, 3.2; 95% confidence limit, 1.4-40). BRCA1/2 mutation carriers with ovarian cancer were only about one half as likely to carry the RAD51:135 g-->c SNP. Analysis of the RAD51:135 g-->c SNP in 738 subjects from an Israeli ovarian cancer case-control study was consistent with a lower risk of ovarian cancer among BRCA1/2 mutation carriers with the c allele. We have identified a RAD51 5' untranslated region SNP that may be associated with an increased risk of breast cancer and a lower risk of ovarian cancer among BRCA2 mutation carriers. The biochemical basis of this risk modifier is currently unknown.

The GRIP domain is a specific targeting sequence for a population of trans-Golgi network derived tubulo-vesicular carriers

Vesicular carriers for intracellular transport associate with unique sets of accessory molecules that dictate budding and docking on specific membrane domains. Although many of these accessory molecules are peripheral membrane proteins, in most cases the targeting sequences responsible for their membrane recruitment have yet to be identified. We have previously defined a novel Golgi targeting domain (GRIP) shared by a family of coiled-coil peripheral membrane Golgi proteins implicated in membrane trafficking. We show here that the docking site for the GRIP motif of p230 is a specific domain of Golgi. membranes. By immunoelectron microscopy of HeLa cells stably expressing a green fluorescent protein (GFP)-p230(GRIP) fusion protein, we show binding specifically to a subset of membranes of the trans-Golgi network (TGN). Real-time imaging of live HeLa cells revealed that the GFP-p230(GRIP) was associated with highly dynamic tubular extensions of the TGN, which have the appearance and behaviour of transport carriers. To further define the nature of the GRIP membrane binding site, in vitro budding assays were performed using purified rat liver Golgi membranes and cytosol from GFP-p230(GRIP) transfected cells. Analysis of Golgi-derived vesicles by sucrose gradient fractionation demonstrated that GFP-p230(GRIP) binds to a specific population of vesicles distinct from those labelled for beta -COP or gamma -adaptin. The GFP-p230(GRIP) fusion protein is recruited to the same vesicle population as full-length p230, demonstrating that the GRIP domain is solely proficient as a targeting signal for membrane binding of the native molecule. Therefore, p230 GRIP is a targeting signal for recruitment to a highly selective membrane attachment site on a specific population of trans-Golgi network tubulovesicular carriers.

Ex vivo profiling of CD8(+)-T-cell responses to human cytomegalovirus reveals broad and multispecific reactivities in healthy virus carriers

Human cytomegalovirus (HCMV) can establish both nonproductive (latent) and productive (lytic) infections. Many of the proteins expressed during these phases of infection could be expected to be targets of the immune response; however, much of our understanding of the CD8(+)-T-cell response to HCMV is mainly based on the pp65 antigen. Very little is known about T-cell control over other antigens expressed during the different stages of virus infection; this imbalance in our understanding undermines the importance of these antigens in several aspects of HCMV disease pathogenesis. In the present study, an efficient and rapid strategy based on predictive bioinformatics and ex vivo functional T-cell assays was adopted to profile CD8(+)-T-cell responses to a large panel of HCMV antigens expressed during different phases of replication. These studies revealed that CD8(+)-T-cell responses to HCMV often contained multiple antigen-specific reactivities, which were not just constrained to the previously identified pp65 or IE-1 antigens. Unexpectedly, a number of viral proteins including structural, early/late antigens and HCMV-encoded immunomodulators (pp28, pp50, gH, gB, US2, US3, US6, and UL18) were also identified as potential targets for HCMV-specific CD8(+)-T-cell immunity. Based on this extensive analysis, numerous novel HCMV peptide epitopes and their HLA-restricting determinants recognized by these T cells have been defined. These observations contrast with previous findings that viral interference with the antigen-processing pathway during lytic infection would render immediate-early and early/late proteins less immunogenic. This work strongly suggests that successful HCMV-specific immune control in healthy virus carriers is dependent on a strong T-cell response towards a broad repertoire of antigens.

GAIP participates in budding of membrane carriers at the trans-Golgi network

Galpha interacting protein (GAIP) is a regulator of G protein signaling protein that associates dynamically with vesicles and has been implicated in membrane trafficking, although its specific role is not yet known. Using an in vitro budding assay, we show that GAIP is recruited to a specific population of trans-Golgi network-derived vesicles and that these are distinct from coatomer or clathrin-coated vesicles. A truncation mutant (NT-GAIP) encoding only the N-terminal half of GAIP is recruited to trans -Golgi network membranes during the formation of vesicle carriers. Overexpression of NT-GAIP induces the formation of long, coated tubules, which are stabilized by microtubules. Results from the budding assay and from imaging in live cells show that these tubules remain attached to the Golgi stack rather than being released as carrier vesicles. NT-GAIP expression blocks membrane budding and results in the accumulation of tubular carrier intermediates. NT-GAIP-decorated tubules are competent to load vesicular stomatitis virus protein G-green fluorescent protein as post-Golgi, exocytic cargo and in cells expressing NT-GAIP there is reduced surface delivery of vesicular stomatitis virus protein G-green fluorescent protein. We conclude that GAIP functions as an essential part of the membrane budding machinery for a subset of post-Golgi exocytic carriers derived from the trans-Golgi network.

An investigation into support for restrictions on HIV carriers in the Chicago metropolitan area

An investigation into support for restrictions on people testing seropositive for HIV is reported on. Data were collected during telephone interviews with two-hundred adults aged eighteen to sixty-five in the Chicago metropolitan area. Using the analytic technique of LISREL, six models which attempt to explain support for restrictions were tested. It was found that the model best supported by the data indicates that two groups contribute to support for restrictions on HIV carriers - one due to intolerance of homosexuality and one to mistrust of public health officials regarding their control and management of the AIDS epidemic. The relevance of these findings for public health policy makers is discussed.