Refractory periods and climate forcing in cholera dynamics

Outbreaks of many infectious diseases, including cholera, malaria and dengue, vary over characteristic periods longer than 1 year. Evidence that climate variability drives these interannual cycles has been highly controversial, chiefly because it is difficult to isolate the contribution of environmental forcing while taking into account nonlinear epidemiological dynamics generated by mechanisms such as host immunity. Here we show that a critical interplay of environmental forcing, specifically climate variability, and temporary immunity explains the interannual disease cycles present in a four-decade cholera time series from Matlab, Bangladesh. We reconstruct the transmission rate, the key epidemiological parameter affected by extrinsic forcing, over time for the predominant strain (El Tor) with a nonlinear population model that permits a contributing effect of intrinsic immunity. Transmission shows clear interannual variability with a strong correspondence to climate patterns at long periods (over 7 years, for monsoon rains and Brahmaputra river discharge) and at shorter periods (under 7 years, for flood extent in Bangladesh, sea surface temperatures in the Bay of Bengal and the El Ni?o-Southern Oscillation). The importance of the interplay between extrinsic and intrinsic factors in determining disease dynamics is illustrated during refractory periods, when population susceptibility levels are low as the result of immunity and the size of cholera outbreaks only weakly reflects climate forcing.     

Genetic variation in selenoprotein S influences inflammatory response

Chronic inflammation has a pathological role in many common diseases and is influenced by both genetic and environmental factors. Here we assess the role of genetic variation in selenoprotein S (SEPS1, also called SELS or SELENOS), a gene involved in stress response in the endoplasmic reticulum and inflammation control. After resequencing SEPS1, we genotyped 13 SNPs in 522 individuals from 92 families. As inflammation biomarkers, we measured plasma levels of IL-6, IL-1beta and TNF-alpha. Bayesian quantitative trait nucleotide analysis identified associations between SEPS1 polymorphisms and all three proinflammatory cytokines. One promoter variant, -105G --> A, showed strong evidence for an association with each cytokine (multivariate P = 0.0000002). Functional analysis of this polymorphism showed that the A variant significantly impaired SEPS1 expression after exposure to endoplasmic reticulum stress agents (P = 0.00006). Furthermore, suppression of SEPS1 by short interfering RNA in macrophage cells increased the release of IL-6 and TNF-alpha. To investigate further the significance of the observed associations, we genotyped -105G --> A in 419 Mexican American individuals from 23 families for replication. This analysis confirmed a significant association with both TNF-alpha (P = 0.0049) and IL-1beta (P = 0.0101). These results provide a direct mechanistic link between SEPS1 and the production of inflammatory cytokines and suggest that SEPS1 has a role in mediating inflammation.     

Dominant modifier DFNM1 suppresses recessive deafness DFNB26

More than 50% of severe childhood deafness is genetically determined, approximately 70% of which occurs without other abnormalities and is thus termed nonsyndromic. So far, 30 nonsyndromic recessive deafness loci have been mapped and the defective genes at 6 loci, DFNB1, DFNB2, DFNB3, DFNB4, DFNB9 and DNFB21, have been identified, encoding connexin-26 (ref. 3), myosin VIIA (ref. 4), myosin XV (ref. 5), pendrin, otoferlin and alpha-tectorin, respectively. Here we map a new recessive nonsyndromic deafness locus, DFNB26, to a 1.5-cM interval of chromosome 4q31 in a consanguineous Pakistani family. A maximum lod score of 8.10 at theta=0 was obtained with D4S1610 when only the 8 affected individuals in this family were included in the calculation. There are seven unaffected family members who are also homozygous for the DFNB26-linked haplotype and thus are non-penetrant. A dominant modifier, DFNM1, that suppresses deafness in the 7 nonpenetrant individuals was mapped to a 5.6-cM region on chromosome 1q24 with a lod score of 4.31 at theta=0 for D1S2815.     

The influence of oestrogen and thyroid on the pituitary and blood content of FSH and LH

Résumé L'effet de l'administration du «Benzoate d'stradiol» et des hormones thyroïdales seuls ou en combinaison sur le FSH et LH contenus dans le sang et les hypophyses des femelles rats castrés a été étudié. Il a été trouvé que l'stradiol et l'extract de la thyroïde quand ils sont administrés seuls produisent une baisse, dans le sang, du FSH et une hausse du LH. L'administration combinée de ces deux hormones renforce cet effet.     

Influence of estrogen and progesterone on the oxygen consumption of rats,with reference to the role played by the thyroid

Résumé Une seule dose de 2 g d'estradiol a augmenté la consommation d'oxygène des rats castrés, seulement quand les thyroïdes étaient intactes. Une dose unique de 0,40 mg de progestérone a augmenté aussi la consommation d'oxygène des rats castrés, en présence ou absence des thyroïdes. A ces doses, il n'y a ni synergisme ni antagonisme entre l'estrogène et le progestérone dans leur influence sur la consommation d'oxygène.     

Ovarian serotonin content in relation to ovulation

Summary In the mature cyclic female rat, analysis for ovarian serotonin content reveals comparatively high serotonin content. Fluctuation of serotonin content was observed; peak for serotonin was observed at estrus. In gonadotropintreated immature rats, there was no detected ovarian serotonin using this procedure. It was concluded that ovaries from gonadotropin-treated immature rats are physiologically different from ovaries taken from mature cyclic rats.Supported by NIH Grant RR8111.National Institutes of Health, MBS Trainee.     

The involvement of serotonin in induced ovulation in the immature rat

Summary In pregnant mare's serum gonadotropin (PMS) treated immature rats the cortex, cerebellum, caudate nucleus and hypothalamus were isolated and analyzed for their serotonin (5-HT) content at 6-h intervals for 72 h. Results showed a general trend of significant variation occurring in days 1 and 3 after PMS injection with no major variations observed on the second day. The results obtained suggest a possible involvement of 5-HT in the control of ovulation.