The BsmI vitamin D receptor gene polymorphism is associated with ulcerative colitis in Jewish Ashkenazi patients

Susceptibility to inflammatory bowel disease (IBD) has a strong genetic component. The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be associated with IBD in some studies. In this case-control study we determined the association between the BsmI VDR gene polymorphism and IBD in patients with Crohn's disease (CD) and ulcerative colits (UC). Three hundred seventy-nine Jewish Israeli patients with IBD, 228 with CD (129 Ashkenazi and 99 non-Ashkenazi), and 151 patients with UC (72 Ashkenazi, 79 non-Ashkenazi) were studied. The control group included 495 healthy blood donors (352 non-Ashkenazi and 143 Ashkenazi). All subjects were genotyped for the BsmI VDR gene polymorphism. The frequency of the BB genotype was higher in Ashkenazi patients with UC compared to Ashkenazi controls (0.21 vs. 0.11, p = 0.042, odds ratio 2.27, 95% confidence interval [CI] 1.06-4.9). There were no differences in the prevalence of the BB genotype or the B allele between ethnically matched patients with CD and UC. Nor were there differences in the BB genotype or B allele frequencies between CD patients and ethnically matched controls. The BsmI VDR gene polymorphism is associated with increased susceptibility to UC in Israeli Ashkenazi patients with UC.     

Heterodimerization,Altered Subcellular Localization,and Function of Multiple Zinc Transporters in Viable Cells Using Bimolecular Fluorescence Complementation

Zinc plays a crucial role in numerous key physiological functions. Zinc transporters (ZnTs) mediate zinc efflux and compartmentalization in intracellular organelles; thus, ZnTs play a central role in zinc homeostasis. We have recently shown the in situ dimerization and function of multiple normal and mutant ZnTs using bimolecular fluorescence complementation (BiFC). Prompted by these findings, we here uncovered the heterodimerization, altered subcellular localization, and function of multiple ZnTs in live cells using this sensitive BiFC technique. We show that ZnT1, -2, -3, and -4 form stable heterodimers at distinct intracellular compartments, some of which are completely different from their homodimer localization. Specifically, unlike the plasma membrane (PM) localization of ZnT1 homodimers, ZnT1-ZnT3 heterodimers localized at intracellular vesicles. Furthermore, upon heterodimerization with ZnT1, the zinc transporters ZnT2 and ZnT4 surprisingly localized at the PM, as opposed to their vesicular homodimer localization. We further demonstrate the deleterious effect that the G87R-ZnT2 mutation, associated with transient neonatal zinc deficiency, has on ZnT1, ZnT3, and ZnT4 upon heterodimerization. The functionality of the various ZnTs was assessed by the dual BiFC-Zinquin assay. We also undertook a novel transfection competition assay with ZnT cDNAs to confirm that the driving force for heterodimer formation is the core structure of ZnTs and not the BiFC tags. These findings uncover a novel network of homo- and heterodimers of ZnTs with distinct subcellular localizations and function, hence highlighting their possible role in zinc homeostasis under physiological and pathological conditions.     

Learning is improved by a soybean oil diet in rats

A semi-synthetic diet containing 20% polyunsaturated fat (soybean) oil was fed to young male hooded rats for 21 days. These animals exhibited improved performance on an environmentally-cued testing paradigm which is thought to reflect cognitive learning skills (i.e., Place Navigation Water Task). Other rats fed the same base diet but containing 20% saturated fat (lard) showed no such improvement compared to chow-fed (4.5% mixed fat) controls. The animals fed soybean oil also exhibited a transient resistance to extinguish this learning. This improved learning could not be explained by changes in general motor activity, basal body temperature, energy consumption, body weight, or in the brain activity of choline acetyltransferase, the marker enzyme for cholinergic neurons. These findings constitute the first evidence that short-term variations in the quality of dietary fat can enhance mammalian learning.     

Conformational changes and loose packing promote E. coli Tryptophanase cold lability

Background  

Oligomeric enzymes can undergo a reversible loss of activity at low temperatures. One such enzyme is tryptophanase (Trpase) from Escherichia coli. Trpase is a pyridoxal phosphate (PLP)-dependent tetrameric enzyme with a Mw of 210 kD. PLP is covalently bound through an enamine bond to Lys270 at the active site. The incubation of holo E. coli Trpases at 2°C for 20 h results in breaking this enamine bond and PLP release, as well as a reversible loss of activity and dissociation into dimers. This sequence of events is termed cold lability and its understanding bears relevance to protein stability and shelf life.     

α-Adrenergic stimulants, prostaglandins and catecholamine release from the adrenal gland in vitro

Prostaglandin D₂ was found to be a potent inhibitor of platelet aggregation. Aggregation of human platelets by ADP, collagen and prostaglandin G₂ was inhibited more strongly by PGD₂ than by PGE₁. Although ADP-induced aggregation of rabbit platelets was inhibited more strongly by PGE₁ than by PGD₂ the latter prostaglandin gave a more long-lasting inhibitory effect on platelet aggregation following intravenous or oral administration. These results coupled with the finding that PGD₂ has less hypotensive effects on the cardiovascular system than PGE₁ suggest the possible use of PGD₂ as an antithrombotic agent.     

α-Adrenergic stimulants, prostaglandins and catecholamine release from the adrenal gland in vitro

In rat adrenal glands incubated in Locke's solution in vitro norepinephrine and phenylephrine inhibited the release of epinephrine. PGE₂ and PGE₁ also inhibited the release of catecholamines but PGF_α1 had no effect on the adrenal. Thus, catecholamine release from adrenal cells may be regulated by the same mechanisms as in adrenergic nerve endings.     

Geographical Variability in the Likelihood of Bloodstream Infections Due to Gram-Negative Bacteria: Correlation with Proximity to the Equator and Health Care Expenditure

ObjectiveInfections due to Gram-negative bacteria exhibit seasonal trends, with peak infection rates during warmer months. We hypothesized that the likelihood of a bloodstream infection due to Gram-negative bacteria increases with proximity to the equator. We tested this hypothesis and identified geographical, climatic and social factors associated with this variability.DesignWe established a network of 23 international centers in 22 cities. Setting: De-identified results of positive blood cultures from 2007–2011 and data sources for geographic, climatic and socioeconomic factors were assembled for each center.ParticipantsPatients at the 23 centers with positive blood cultures.ResultsThe mean fraction of bacteremia associated with Gram-negative bacteria was 48.4% (range 26.4% to 61.8%). Although not all sites displayed significant seasonality, the overall P-value for seasonal oscillation was significant (P<0.001). In univariate meta-regression models, temperature, latitude, latitude squared, longitude, per capita gross domestic product and percent of gross domestic product spent on healthcare were all associated with the fraction of bacteremia due to Gram-negative bacteria. In multivariable models, only percent of gross domestic product spent on healthcare and distance from the equator (ie. latitude squared) were significantly associated with the fraction of bacteremia due to Gram-negative bacteria.ConclusionsThe likelihood of bacteremia due to Gram-negative bacteria varies markedly between cities, in a manner that appears to have both geographic (latitude) and socioeconomic (proportion gross domestic product devoted to health spending) determinants. Thus, the optimal approach to initial management of suspected bacteremia may be geographically specific. The rapid emergence of highly antibiotic-resistant Gram-negative pathogens may have geographically specific impacts.