Circadian rhythm in cerebral blood volume of mouse

Zusammenfassung Mittels I¹³¹ markiertem Human-Serumalbumin wurde das Blutvolumen im Gehirn von Mäusen zu verschiedenen Tageszeiten gemessen und eine circadiane Rhythmik festgestellt. Andauernder Dunkelaufenthalt führt zu erhöhten Werten des Blutvolumens.     

Exudative diathesis produced by vitamin e-deficient diets without polyenoic fatty acids

Zusammenfassung Bei Fütterung von Küken mit einer Vitamin-E-freien Nahrung, die als Eiweissquelle eine spezielle Trockenhefe, frei von mehrfach ungesättigten Fettsäuren, enthielt, wurde eine jedoch verhältnismässig milde, exsudative Diathese beobachtet.     

豚鼠耳蜗基底膜的振动特性

为探讨豚鼠耳蜗基底膜的听觉机制,利用多普勒激光测振技术进行了声音在28只成年健康豚鼠耳中传递的测试实验.将豚鼠麻醉后切断头取出听泡,采用电钻暴露其耳蜗基底膜,利用多普勒激光测振仪在给定的声压级、频率的纯音激励条件下测量豚鼠外耳道耳蜗基底膜的振动速度,并测量了中耳镫骨的振动速度.结果表明,豚鼠外耳道基底膜具有频率选择特性,而且其基底膜的振动具有行波特性.     

Dwarf8 polymorphisms associate with variation in flowering time.

Historically, association tests have been used extensively in medical genetics, but have had virtually no application in plant genetics. One obstacle to their application is the structured populations often found in crop plants, which may lead to nonfunctional, spurious associations. In this study, statistical methods to account for population structure were extended for use with quantitative variation and applied to our evaluation of maize flowering time. Mutagenesis and quantitative trait locus (QTL) studies suggested that the maize gene Dwarf8 might affect the quantitative variation of maize flowering time and plant height. The wheat orthologs of this gene contributed to the increased yields seen in the 'Green Revolution' varieties. We used association approaches to evaluate Dwarf8 sequence polymorphisms from 92 maize inbred lines. Population structure was estimated using a Bayesian analysis of 141 simple sequence repeat (SSR) loci. Our results indicate that a suite of polymorphisms associate with differences in flowering time, which include a deletion that may alter a key domain in the coding region. The distribution of nonsynonymous polymorphisms suggests that Dwarf8 has been a target of selection.     

TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis

Although there has been much success in identifying genetic variants associated with common diseases using genome-wide association studies (GWAS), it has been difficult to demonstrate which variants are causal and what role they have in disease. Moreover, the modest contribution that these variants make to disease risk has raised questions regarding their medical relevance. Here we have investigated a single nucleotide polymorphism (SNP) in the TNFRSF1A gene, that encodes tumour necrosis factor receptor 1 (TNFR1), which was discovered through GWAS to be associated with multiple sclerosis (MS), but not with other autoimmune conditions such as rheumatoid arthritis, psoriasis and Crohn’s disease. By analysing MS GWAS data in conjunction with the 1000 Genomes Project data we provide genetic evidence that strongly implicates this SNP, rs1800693, as the causal variant in the TNFRSF1A region. We further substantiate this through functional studies showing that the MS risk allele directs expression of a novel, soluble form of TNFR1 that can block TNF. Importantly, TNF-blocking drugs can promote onset or exacerbation of MS, but they have proven highly efficacious in the treatment of autoimmune diseases for which there is no association with rs1800693. This indicates that the clinical experience with these drugs parallels the disease association of rs1800693, and that the MS-associated TNFR1 variant mimics the effect of TNF-blocking drugs. Hence, our study demonstrates that clinical practice can be informed by comparing GWAS across common autoimmune diseases and by investigating the functional consequences of the disease-associated genetic variation.     

mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake

How adult tissue stem and niche cells respond to the nutritional state of an organism is not well understood. Here we find that Paneth cells, a key constituent of the mammalian intestinal stem-cell (ISC) niche, augment stem-cell function in response to calorie restriction. Calorie restriction acts by reducing mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells, and the ISC-enhancing effects of calorie restriction can be mimicked by rapamycin. Calorie intake regulates mTORC1 in Paneth cells, but not ISCs, and forced activation of mTORC1 in Paneth cells during calorie restriction abolishes the ISC-augmenting effects of the niche. Finally, increased expression of bone stromal antigen 1 (Bst1) in Paneth cells—an ectoenzyme that produces the paracrine factor cyclic ADP ribose—mediates the effects of calorie restriction and rapamycin on ISC function. Our findings establish that mTORC1 non-cell-autonomously regulates stem-cell self-renewal, and highlight a significant role of the mammalian intestinal niche in coupling stem-cell function to organismal physiology.     

Thallium isotopic evidence for ferromanganese sediments in the mantle source of Hawaiian basalts

Ocean island basalts are generally thought to be the surface expression of mantle plumes, but the nature of the components in the source regions of such mantle plumes is a subject of long-standing debate. The lavas erupted at Hawaii have attracted particular attention, as it has been proposed that coupled 186Os and 187Os anomalies reflect interaction with the Earth's metallic core. It has recently been suggested, however, that such variations could also result from addition of oceanic ferromanganese sediments to the mantle source of these lavas. Here we show that Hawaiian picrites with osmium isotope anomalies also exhibit pronounced thallium isotope variations, which are coupled with caesium/thallium ratios that extend to values much lower than commonly observed for mantle-derived rocks. This correlation cannot be created by admixing of core material, and is best explained by the addition of ferromanganese sediments into the Hawaii mantle source region. However, the lack of correlation between thallium and osmium isotopes and the high thallium/osmium ratios of ferromanganese sediments preclude a sedimentary origin for the osmium isotope anomalies, and leaves core-mantle interaction as a viable explanation for the osmium isotope variations of the Hawaiian picrites.