Medical Research Council

About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.

Genetic variation in LIN28B is associated with the timing of puberty

Abstract: The timing of puberty is highly variable(1). We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor a ...

Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology.

Abstract: Genome-wide association studies (GWAS) have identified a region upstream the BIN1 gene as the most important genetic susceptibility locus in Alzheimer’s disease (AD) after APOE. We report that BIN1 transcript levels were increased in AD brains and identified a novel 3 bp insertion allele ~28 kb upstream of BIN1, which increased (i) transcriptional activity in vitro, (ii) BIN1 expression levels in human brain and (iii) AD risk in three independent case-control cohorts (Meta-analysed Odds ratio of 1.20 (1.14–1.26) (P=3.8 × 10−11)). Interestingly, decreased expression of the Drosophila BIN1 ortholog Amph suppressed Tau-mediated neurotoxicity in three different assays. Accordingly, Tau and BIN1 colocalized and interacted in human neuroblastoma cells and in mouse brain. Finally, the 3 bp insertion was associated with Tau but not Amyloid loads in AD brains. We propose that BIN1 mediates AD risk by modulating Tau pathology.

The capacity for generating information by randomization.

Abstract: Response selection was studied independently of the stimulus by asking subjects to generate random sequences of letters or numbers. Experiment 1 varied rate of letter generation from ½ sec. to 4 se...

Inhibin B as a serum marker of spermatogenesis: correlation to differences in sperm concentration and follicle-stimulating hormone levels. A study of 349 Danish men

Abstract: Recent studies have focused on reproductive health of men in the general population. However, semen samples are difficult to obtain within sampling frames that allow comparisons. Blood samples are easier to obtain than ejaculates. Therefore, serum biomarkers of spermatogenesis are of major interest for population studies. FSH has previously been used as a marker of spermatogenesis, although it is also influenced by the hypothalamus. Serum inhibin B was recently suggested as a possible, more direct serum marker of spermatogenesis in men with testicular disorders. In a Danish nationwide collaborative study, we found an unexpected difference in semen concentration between two groups of men recruited from two different centres. We, therefore, analyzed reproductive hormones in blood, including inhibin B, to test whether the observed difference in semen concentration was reflected in the reproductive hormones. From 1992 to 1995, a total of 430 men, 20-35 yr old, who lived with a partner and who had not previously attempted to achieve a pregnancy, were recruited. The couples were enrolled into the study in one of two centres (centre A, n = 231; and centre B, n = 199) when they discontinued birth control. At enrollment, they provided a semen sample (n = 419), and a blood sample was drawn (n = 349). The semen analysis was performed in accordance with the WHO 1992 guidelines, and interlaboratory differences were tested. Inhibin B was measured in an enzyme immunometric assay, which has previously been described. All blood samples were analyzed in the same laboratory. Median sperm concentration and the percentage of morphologically normal spermatozoa were significantly higher among men from centre A (56.0 mill/mL and 42.5%), compared with men from centre B (44.8 mill/mL and 39%). Men from centre B had a significantly higher median FSH (3.42 IU/L) and a lower inhibin B (186 pg/mL) than men from centre A (3.21 IU/L and 209 pg/mL). The differences persisted after control for potentially confounding variables. A significant correlation was found between the cubic root-transformed serum FSH and inhibin B levels (r = -0.61, P < 0.001), between the cubic root-transformed serum FSH and sperm concentration (r = -0.40, P < 0.001), and between the cubic root-transformed inhibin B and sperm concentration (r = 0.38, P < 0.001). The predictive power of detecting sperm counts below 20 mill/mL among men who's inhibin B and FSH both were below 80 pg/mL and above 10 IU/L, respectively, was 100%. The unexpected significant difference in semen concentration between two groups of normal Danish men was probably caused by differences in sampling procedures in the two centres where the men were recruited, rather than geographical differences. However, similar differences in serum levels of inhibin B and FSH between centres were found. These findings suggest that a real difference in spermatogenic potential between the two groups of men existed. We suggest that serum inhibin B, in future population studies on male reproductive health, may serve as a new marker of spermatogenesis, in addition to sperm concentration and serum FSH.