Insulin processing and action in adipocytes: evidence for generation of insulin-containing vesicles by leupeptin and monensin

AbstractIncubation of adipocytes with 125I-insulin plus leupeptin or monensin, but not chloroquine, resulted in the appearance of a novel peak of 125I-insulin (modal density about 1.20 gml) on density gradient centrifugation; the appearance of the peak depended on the presence of specific insulin receptors on the cell surface. The fractions comprising this peak contained vesicles, probably originating from the Golgi apparatus, and dit not appear to be contaminated with lysosomes, mitochondria or plasma membrane. Entrapment of insulin in these vesicles per se did not prevent the activation of glucose transport, acetyl-CoA carboxylase or pyruvate dehydrogenase by insulin

Two Different, Highly Exposed, Bulged Structures for an Unusually Long Peptide Bound to Rat MHC Class I RT1-Aa

AbstractThe rat MHC class Ia molecule RT1-Aa has the unusual capacity to bind long peptides ending in arginine, such as MTF-E, a thirteen-residue, maternally transmitted minor histocompatibility antigen. The antigenic structure of MTF-E was unpredictable due to its extraordinary length and two arginines that could serve as potential anchor residues. The crystal structure of RT1-Aa-MTF-E at 2.55 Å shows that both peptide termini are anchored, as in other class I molecules, but the central residues in two independent pMHC complexes adopt completely different bulged conformations based on local environment. The MTF-E epitope is fully exposed within the putative T cell receptor (TCR) footprint. The flexibility demonstrated by the MTF-E structures illustrates how different TCRs may be raised against chemically identical, but structurally dissimilar, pMHC complexes

Measuring and preliminary modeling of drift interception by plant species

Currently, the concept of plant capture efficiency is not quantitatively considered in the evaluation of off-target drift for the purposes of pesticide risk assessment in the United States. For on-target pesticide applications, canopy capture efficiency is managed by optimizing formulations or tank-mixing with adjuvants to maximize retention of spray droplets. These efforts take into consideration the fact that plant species have diverse morphology and surface characteristics, and as such will retain varying levels of applied pesticides. This work aims to combine plant surface wettability potential, spray droplet characteristics, and plant morphology into describing the plant capture efficiency of drifted spray droplets. In this study, we used wind tunnel experiments and individual plants grown to 10–20 cm to show that at two downwind distances and with two distinct nozzles capture efficiency for sunflower (Helianthus annuus L.), lettuce (Lactuca sativa L.), and tomato (Solanum lycopersicum L.) is consistently higher than rice (Oryza sativa L.), peas (Pisum sativum L). and onions (Allium cepa L.), with carrots (Daucus carota L.) showing high variability and falling between the two groups. We also present a novel method for three-dimensional modeling of plants from photogrammetric scanning and use the results in the first known computational fluid dynamics simulations of drift capture efficiency on plants. The mean simulated drift capture efficiency rates were within the same order of magnitude of the mean observed rates of sunflower and lettuce, and differed by one to two orders for rice and onion. We identify simulating the effects of surface roughness on droplet behavior, and the effects of wind flow on plant movement as potential model improvements requiring further species-specific data collection

Increased police patrols for preventing alcohol-impaired driving.

BACKGROUND: Road traffic injuries cause 1.2 million deaths worldwide each year. Alcohol consumption increases the risk of traffic crashes, especially fatal crashes. Increased police patrols aim to increase both the perceived and actual likelihood of being caught driving while alcohol-impaired, potentially reducing alcohol-related driving, crashes and injuries. OBJECTIVES: To assess the effects on injuries and crashes of increased police patrols that target alcohol-impaired driving. SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised Register (5/2006), CENTRAL (The Cochrane Library 2006, Issue 2), MEDLINE (1966 to 5/2006), TRANSPORT (1968 to 5/2006), C2-SPECTR (2/2005), NCJRS (1/1951 to 5/2006), PsycINFO (1872 to 5/2006), Social Science Citation Index (1974 to 5/2006), SIGLE (1980 to 2/2006), Science Citation Index Expanded (1970 to 5/2006), Dissertation Abstracts (1870 to 5/2006), NTIS (1964 to 12/2004), conference proceedings, and reference lists. We contacted authors of eligible studies. SELECTION CRITERIA: Randomized controlled trials, controlled trials, controlled before and after studies, interrupted time series (ITS) studies, and controlled ITS studies evaluating increased police patrols, either alone or combined with other interventions, targeting alcohol-impaired motor vehicle drivers. DATA COLLECTION AND ANALYSIS: Two investigators independently screened citations, extracted data, and assessed quality criteria. We compared intervention and no-intervention geographical areas or time periods. We re-analyzed study data as required. Results are presented narratively. MAIN RESULTS: The 32 eligible studies included one randomized controlled trial, eight controlled before-after studies, 14 controlled ITS studies, six ITS studies, and three studies with both ITS and controlled before-after analyses. Most interventions targeted only alcohol-impaired driving (69%) and included additional interventions such as media campaigns or special training for police officers (91%). Only two studies reported sufficient information to assess study quality completely. Two-thirds of studies were scored 'not adequate' on at least one feature. Five of six studies evaluating traffic fatalities reported reductions with the intervention, but differences were statistically significant in only one study. Effects of intervention on traffic injuries were inconsistent in the six studies evaluating this outcome, and no results were statistically significant. All four controlled studies evaluating fatal crashes reported reductions with the intervention, which were statistically significant in one study. All 12 controlled studies assessing injury crashes reported greater reductions with the intervention, though effects were minimal or not significant in several studies. ITS studies showed less consistent effects on fatal crashes (three studies) and injury crashes (four studies), and effect estimates were typically imprecise. Thirteen of 20 studies showed reductions in total crashes and about two-thirds of these were statistically significant. AUTHORS' CONCLUSIONS: Studies examining increased police patrol programs were generally consistent in reporting beneficial effects on traffic crashes and fatalities, but study quality and reporting were often poor. Methodological limitations included inadequate sample size, dissimilar baseline measures, contamination, and inadequate data analysis. Thus existing evidence, although supportive, does not firmly establish whether increased police patrols, implemented with or without other intervention elements, reduce the adverse consequences of alcohol-impaired driving

Nonparametric methods for the analysis of single-color pathogen microarrays

<p>Abstract</p> <p>Background</p> <p>The analysis of oligonucleotide microarray data in pathogen surveillance and discovery is a challenging task. Target template concentration, nucleic acid integrity, and host nucleic acid composition can each have a profound effect on signal distribution. Exploratory analysis of fluorescent signal distribution in clinical samples has revealed deviations from normality, suggesting that distribution-free approaches should be applied.</p> <p>Results</p> <p>Positive predictive value and false positive rates were examined to assess the utility of three well-established nonparametric methods for the analysis of viral array hybridization data: (1) Mann-Whitney <it>U</it>, (2) the Spearman correlation coefficient and (3) the chi-square test. Of the three tests, the chi-square proved most useful.</p> <p>Conclusions</p> <p>The acceptance of microarray use for routine clinical diagnostics will require that the technology be accompanied by simple yet reliable analytic methods. We report that our implementation of the chi-square test yielded a combination of low false positive rates and a high degree of predictive accuracy.</p

Redefining Renal Cell Carcinoma: A Molecular Perspective on Classification and Clinical Implications

Renal cell carcinoma (RCC) is the most common primary tumour of the kidney. RCC is a clinically and pathologically heterogenous entity, which has traditionally been classified under two broad categories: clear-cell and non-clear cell. With improved molecular diagnostic methodologies and genetic testing, the classification of RCC has shifted from a morphological basis to a molecular/genetic focus, and has been systematically updated to reflect these advancements. The new 2022 World Health Organization (WHO) classification of RCC is the most recent of these updates, and contains significant changes, as compared to the previous 2016 classification. The most substantial of these changes is the establishment of a new category of molecularly-defined RCC, including TFE3-rearranged RCC, TFEB-altered RCC, ELOC-mutated RCC, fumarate hydratase-deficient RCC, succinate dehydrogenase-deficient RCC, ALK-rearranged RCC, and SMARCB1-deficient renal medullary carcinoma. In this narrative review, the authors briefly summarise the histopathological characteristics, clinical course, current treatment standards, and future treatment directions of each of these molecularly-defined RCC subtypes