Insulin but not PDGF relies on actin remodeling and on VAMP2 for GLUT4 translocation in myoblasts

Insulin promotes the translocation of glucose transporter 4 (GLUT4) from intracellular pools to the surface of muscle and fat cells via a mechanism dependent on phosphatidylinositol (PtdIns) 3-kinase, actin cytoskeletal remodeling and the v-SNARE VAMP2. The growth factor PDGF-BB also robustly activates PtdIns 3-kinase and induces actin remodeling, raising the question of whether it uses similar mechanisms to insulin in mobilizing GLUT4. In L6 myoblasts stably expressing Myc-tagged GLUT4, neither stimulus affected the rate of GLUT4 endocytosis, confirming that they act primarily by enhancing exocytosis to increase GLUT4 at the cell surface. Although surface GLUT4myc in response to insulin peaked at 10 minutes and remained steady for 30 minutes, PDGF action was transient, peaking at 5 minutes and disappearing by 20 minutes. These GLUT4myc translocation time courses mirrored that of phosphorylation of Akt by the two stimuli. Interestingly, insulin and PDGF caused distinct manifestations of actin remodeling. Insulin induced discrete, long (>5 microm) dorsal actin structures at the cell periphery, whereas PDGF induced multiple short (70% but did not affect the PDGF response. These results suggest that insulin and PDGF rely differently on the actin cytoskeleton and on tetanus-toxin-sensitive VAMPs for mobilizing GLUT4

A multi-centre qualitative study exploring the experiences of UK South Asian and White Diabetic Patients referred for renal care

Background An exploration of renal complications of diabetes from the patient perspective is important for developing quality care through the diabetic renal disease care pathway. Methods Newly referred South Asian and White diabetic renal patients over 16 years were recruited from nephrology outpatient clinics in three UK centres - Luton, West London and Leicester – and their experiences of the diabetes and renal care recorded. A semi-structured qualitative interview was conducted with 48 patients. Interview transcripts were analysed thematically and comparisons made between the White and South Asian groups. Results 23 South Asian patients and 25 White patients were interviewed. Patient experience of diabetes ranged from a few months to 35 years with a mean time since diagnosis of 12.1 years and 17.1 years for the South Asian and White patients respectively. Confusion emerged as a response to referral shared by both groups. This sense of confusion was associated with reported lack of information at the time of referral, but also before referral. Language barriers exacerbated confusion for South Asian patients. Conclusions The diabetic renal patients who have been referred for specialist renal care and found the referral process confusing have poor of awareness of kidney complications of diabetes. Healthcare providers should be more aware of the ongoing information needs of long term diabetics as well as the context of any information exchange including language barriers

Determination of Molecular Dissociation Rates from Measurements of Scattered Solar Ultraviolet Light

Scattereds olaru ltravioletl ight in the spectral region from 250 to 320 nm was measured from a balloon platform at altitudes ranging from 14.5 to 38.8 km with a wavelengthr esolutiono f approximately0 .3 nm and an accuracyin determiningth ew avelengthp ositiono f 0.5 nm. We usedt heses catterd atat o comparea ndv alidatea single scatteringm odel developedf or this purpose. Using these semi-empiricarl esults,w e constructedth e singles cattered component of the ultraviolet irradiance as a function of height and wavelength. From these data, it is possible to determinet he percentaged issociationra te of a variety of speciesd ue to scatteredu ltravioletr adiation. Theser esults are presenteda s a ratio of intensitiesR = I•/(I0+I0, where I• is the first order scatteringa nd I0 is the direct attenuated radiation from the sun. The attenuated direct radiation from the sun can be multiplied by the factor 1/(l-R), the Rayleigha mplificationr atio usedb y Nicolet et al. (1982), to include the contribution to the irradiance from first order scattered light. The results are multiplied by a cross sectiono f the speciesu nder considerationto obtain the dissociationra tes. Ozoneo verburdena nd an approximate ozone particle density altitude profile are obtained when validating the single scatter model

High-resolution radiation hybrid mapping in wheat: an essential tool for the construction of the wheat physical maps

ArtigoO poema épico da época moderna nasce na literatura portuguesa como oceânico logo a partir da sua gestação. Este estudo enquadra a sua génese num contexto europeu.Università di Roma, La Sapienz

Secondary post-geniculate involvement in Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR). Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN) in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P<0.05) and healthy subjects (P<0.01) in OR and not in the other brain regions. Increased OR diffusivity was associated with both disease duration (B\u200a=\u200a0.002; P<0.05) and lack of recovery of visual acuity (B\u200a=\u200a0.060; P<0.01). Post-mortem investigation detected atrophy (41.9\% decrease of neuron soma size in the magnocellular layers and 44.7\% decrease in the parvocellular layers) and, to a lesser extent, degeneration (28.5\% decrease of neuron density in the magnocellular layers and 28.7\% decrease in the parvocellular layers) in the LHON LGN associated with extremely severe axonal loss (99\%) in the optic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons

Glycoprotein gene truncation in avian metapneumovirus subtype C isolates from the United States

The length of the published glycoprotein (G) gene sequences of avian metapneumovirus subtype-C (aMPV-C) isolated from domestic turkeys and wild birds in the United States (1996–2003) remains controversial. To explore the G gene size variation in aMPV-C by the year of isolation and cell culture passage levels, we examined 21 turkey isolates of aMPV-C at different cell culture passages. The early domestic turkey isolates of aMPV-C (aMPV/CO/1996, aMPV/MN/1a-b, and 2a-b/97) had a G gene of 1,798 nucleotides (nt) that coded for a predicted protein of 585 amino acids (aa) and showed >97% nt similarity with that of aMPV-C isolated from Canada geese. This large G gene got truncated upon serial passages in Vero cell cultures by deletion of 1,015 nt near the end of the open reading frame. The recent domestic turkey isolates of aMPV-C lacked the large G gene but instead had a small G gene of 783 nt, irrespective of cell culture passage levels. In some cultures, both large and small genes were detected, indicating the existence of a mixed population of the virus. Apparently, serial passage of aMPV-C in cell cultures and natural passage in turkeys in the field led to truncation of the G gene, which may be a mechanism of virus evolution for survival in a new host or environment

Unique Mass Texture for Quarks and Leptons

Texture specific quark mass matrices which are hermitian and hierarchical are examined in detail . In the case of texture 6 zeros matrices, out of sixteen possibilities examined by us, none is able to fit the low energy data (LED), for example, $V_{us} = 0.2196 \pm 0.0023$, $V_{cb} = 0.0395 \pm 0.0017$, $\frac{V_{ub}}{V_{cb}} = 0.08 \pm 0.02$, $V_{td}$ lies in the range $0.004 - 0.013$ (PDG). Similarly none of the 32 texture 5 zeros mass matrices considered is able to reproduce LED. In particular, the latest data from LEP regarding $|V_{ub}|/|V_{cb}|(=0.093\pm0.016)$ rules out all of them. In the texture 4 zeros case, we find that there is a unique texture structure for $U$ and $D$ mass matrices which is able to fit the data.Comment: 12 pages, LaTeX,some changes in the references,minor changes in the text,to appear in Phys Rev D(Rapid communications

Neutralization Serotyping of BK Polyomavirus Infection in Kidney Transplant Recipients

BK polyomavirus (BKV or BKPyV) associated nephropathy affects up to 10% of kidney transplant recipients (KTRs). BKV isolates are categorized into four genotypes. It is currently unclear whether the four genotypes are also serotypes. To address this issue, we developed high-throughput serological assays based on antibody-mediated neutralization of BKV genotype I and IV reporter vectors (pseudoviruses). Neutralization-based testing of sera from mice immunized with BKV-I or BKV-IV virus-like particles (VLPs) or sera from naturally infected human subjects revealed that BKV-I specific serum antibodies are poorly neutralizing against BKV-IV and vice versa. The fact that BKV-I and BKV-IV are distinct serotypes was less evident in traditional VLP-based ELISAs. BKV-I and BKV-IV neutralization assays were used to examine BKV type-specific neutralizing antibody responses in KTRs at various time points after transplantation. At study entry, sera from 5% and 49% of KTRs showed no detectable neutralizing activity for BKV-I or BKV-IV neutralization, respectively. By one year after transplantation, all KTRs were neutralization seropositive for BKV-I, and 43% of the initially BKV-IV seronegative subjects showed evidence of acute seroconversion for BKV-IV neutralization. The results suggest a model in which BKV-IV-specific seroconversion reflects a de novo BKV-IV infection in KTRs who initially lack protective antibody responses capable of neutralizing genotype IV BKVs. If this model is correct, it suggests that pre-vaccinating prospective KTRs with a multivalent VLP-based vaccine against all BKV serotypes, or administration of BKV-neutralizing antibodies, might offer protection against graft loss or dysfunction due to BKV associated nephropathy

Propagating semantic information in biochemical network models

<p>Abstract</p> <p>Background</p> <p>To enable automatic searches, alignments, and model combination, the elements of systems biology models need to be compared and matched across models. Elements can be identified by machine-readable biological annotations, but assigning such annotations and matching non-annotated elements is tedious work and calls for automation.</p> <p>Results</p> <p>A new method called "semantic propagation" allows the comparison of model elements based not only on their own annotations, but also on annotations of surrounding elements in the network. One may either propagate feature vectors, describing the annotations of individual elements, or quantitative similarities between elements from different models. Based on semantic propagation, we align partially annotated models and find annotations for non-annotated model elements.</p> <p>Conclusions</p> <p>Semantic propagation and model alignment are included in the open-source library semanticSBML, available on sourceforge. Online services for model alignment and for annotation prediction can be used at <url>http://www.semanticsbml.org</url>.</p