Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Virulence spectra of typed strains of Campylobacter jejuni from different sources: a blinded in vivo study

<i>Campylobacter jejuni</i> is a major cause of human diarrhoeal disease, but specific virulence mechanisms have not been well defined. The aims of the present blinded study were to measure and compare the <i>in vivo</i> properties of 40 serotyped, biotyped and genotyped <i>C. jejuni</i> isolates from different sources and genetic makeup. An 11-day-old chick embryo lethality assay, which measured embryo deaths and total viable bacteria over 72 h following inoculation of bacteria into the chorioallantoic membrane, revealed a spectrum of activity within the <i>C. jejuni</i> strains. Human and chicken isolates showed similar high virulence values for embryo deaths while the virulence of the bovine isolates was less pronounced. A one-way ANOVA comparison between the capacity of the strains to kill the chick embryos after 24 h with cytotoxicity towards cultured CaCo-2 cells was significant (<i>P</i>=0.025). After inoculation with a <i>Campylobacter</i> strain, mouse ligated ileal loops were examined histologically and revealed degrees of villous atrophy, abnormal mucosa, dilation of the lumen, congestion and blood in lumen, depending on the isolate examined. A total pathology score', derived for each <i>C. jejuni</i> strain after grading the pathology features for degree of severity, showed no apparent relationship with the source of isolation. Some relationship was found between amplified fragment length polymorphism groups and total ileal loop pathology scores, and a one-way ANOVA comparison of the mouse pathology scores against total chick embryo deaths after 72 h was significant (<i>P</i>=0.049)

Bactericidal action of high-power Nd:YAG laser light on <i>Escherichia coli</i> in saline suspension

Infra-red light (1064 nm) from a high-power Nd:YAG laser caused more than 90% loss of viability of &lt;i&gt;Escherichia coli&lt;/i&gt; during exposures that raised the temperature of PBS suspensions of the bacteria to 50 °C in a thermocouple-equipped cuvette. In contrast, there was minimal loss of viability after heating the same suspensions to 50 °C in a water-bath, or in a PCR thermal cycler. The mechanism of laser killing at 50 °C was explored by differential scanning calorimetry, by laser treatment of transparent and turbid bacterial suspensions, and by optical absorbancy studies of E. coli suspensions at 1064 nm. Taken together, the data suggested that the bactericidal action of Nd:YAG laser light at 50 °C was due partly to thermal heating and partly to an additional, as yet undefined, mechanism. Scanning electron microscopy revealed localized areas of surface damage on laser-exposed &lt;i&gt;E. Coli&lt;/i&gt; cells