Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism

HIF prolyl hydroxylases (PHD1-3) are oxygen sensors that regulate the stability of the hypoxia-inducible factors (HIFs) in an oxygen-dependent manner. Here, we show that loss of Phd1 lowers oxygen consumption in skeletal muscle by reprogramming glucose metabolism from oxidative to more anaerobic ATP production through activation of a Pparalpha pathway. This metabolic adaptation to oxygen conservation impairs oxidative muscle performance in healthy conditions, but it provides acute protection of myofibers against lethal ischemia. Hypoxia tolerance is not due to HIF-dependent angiogenesis, erythropoiesis or vasodilation, but rather to reduced generation of oxidative stress, which allows Phd1-deficient myofibers to preserve mitochondrial respiration. Hypoxia tolerance relies primarily on Hif-2alpha and was not observed in heterozygous Phd2-deficient or homozygous Phd3-deficient mice. Of medical importance, conditional knockdown of Phd1 also rapidly induces hypoxia tolerance. These findings delineate a new role of Phd1 in hypoxia tolerance and offer new treatment perspectives for disorders characterized by oxidative stress.     

欧洲产毒真菌及毒枝菌素研究进展

过去的十多年里，随着人类对自身健康的日益关注，人们对产毒真菌及毒枝菌素研究也在不断深入。欧洲一些与农业相关的研究领域，如植物、食品和饲料等，积累了大量有关产毒真菌及毒枝菌素方面的信息。由于欧洲国家之间环境条件的差异（如温度、光照、降雨等）和自然条件下栽培的作物（谷物品种等）的不同，导致特定产毒真菌在地区分布上的差异，同时也带来了一系列有关真菌毒理学方面的问题。此外，由于世界经济的全球化，农产品的全球贸易对农业有毒真菌的迁移及其可能引发的新疾病，以及地方种群的遗传多样性都将带来深刻的影响。为了便于读者了解过去10—15年间，欧洲有毒真菌及毒枝菌素研究的最新进展，2003年10月25日在意大利举行的“COST-835”会议，本书的编委将这次会议上各国代表的研究论文汇编成册，以飨食读者。     

Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila

Overexpression of sirtuins (NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae), Caenorhabditis elegans and Drosophila melanogaster. Studies of the effects of genes on ageing are vulnerable to confounding effects of genetic background. Here we re-examined the reported effects of sirtuin overexpression on ageing and found that standardization of genetic background and the use of appropriate controls abolished the apparent effects in both C. elegans and Drosophila. In C. elegans, outcrossing of a line with high-level sir-2.1 overexpression abrogated the longevity increase, but did not abrogate sir-2.1 overexpression. Instead, longevity co-segregated with a second-site mutation affecting sensory neurons. Outcrossing of a line with low-copy-number sir-2.1 overexpression also abrogated longevity. A Drosophila strain with ubiquitous overexpression of dSir2 using the UAS-GAL4 system was long-lived relative to wild-type controls, as previously reported, but was not long-lived relative to the appropriate transgenic controls, and nor was a new line with stronger overexpression of dSir2. These findings underscore the importance of controlling for genetic background and for the mutagenic effects of transgene insertions in studies of genetic effects on lifespan. The life-extending effect of dietary restriction on ageing in Drosophila has also been reported to be dSir2 dependent. We found that dietary restriction increased fly lifespan independently of dSir2. Our findings do not rule out a role for sirtuins in determination of metazoan lifespan, but they do cast doubt on the robustness of the previously reported effects of sirtuins on lifespan in C. elegans and Drosophila.     

Taxonomic review of the Amazonian millipede genus Parastenonia Hoffman, 1977 and description of a new species from iron-ore caves (Polydesmida: Chelodesmidae)

ABSTRACT

The Amazonian genus Parastenonia Hoffman, 1977 is here revised. The species P. carajas sp. nov. is described from Brazilian iron-ore caves and P. aurae (Schubart, 1947) is considered junior synonym of P. parae (Cook, 1895). In addition, the known geographic distribution of the genus is presented with the inclusion of new occurrence data.

http://www.zoobank.org/urn:lsid:zoobank.org:act:CCBEED10-DCB4-48C9-A71D-CED3462DD72A     

How Can We Teach the Chemical Elements to Make the Memorization Task More Enjoyable?

In this commentary to Leal (2013), we argue that the memorization of the names and symbols of the chemical elements is necessary in the study of that topic because this task is the key for the later understanding of the Periodic Table. We can make the memorization task in an enjoyable, but effective way, using some educational games in chemistry class. Some recent puzzles, card games, mnemonics rules or games based on drawings to learn the chemical elements are addressed in this paper.     

SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors

The molecular determinants of malignant cell behaviours in breast cancer remain only partially understood. Here we show that SHARP1 (also known as BHLHE41 or DEC2) is a crucial regulator of the invasive and metastatic phenotype in triple-negative breast cancer (TNBC), one of the most aggressive types of breast cancer. SHARP1 is regulated by the p63 metastasis suppressor and inhibits TNBC aggressiveness through inhibition of hypoxia-inducible factor 1α (HIF-1α) and HIF-2α (HIFs). SHARP1 opposes HIF-dependent TNBC cell migration in vitro, and invasive or metastatic behaviours in vivo. SHARP1 is required, and sufficient, to limit expression of HIF-target genes. In primary TNBC, endogenous SHARP1 levels are inversely correlated with those of HIF targets. Mechanistically, SHARP1 binds to HIFs and promotes HIF proteasomal degradation by serving as the HIF-presenting factor to the proteasome. This process is independent of pVHL (von Hippel-Lindau tumour suppressor), hypoxia and the ubiquitination machinery. SHARP1 therefore determines the intrinsic instability of HIF proteins to act in parallel to, and cooperate with, oxygen levels. This work sheds light on the mechanisms and pathways by which TNBC acquires invasiveness and metastatic propensity.     

Late survival of Neanderthals at the southernmost extreme of Europe

The late survival of archaic hominin populations and their long contemporaneity with modern humans is now clear for southeast Asia. In Europe the extinction of the Neanderthals, firmly associated with Mousterian technology, has received much attention, and evidence of their survival after 35 kyr bp has recently been put in doubt. Here we present data, based on a high-resolution record of human occupation from Gorham's Cave, Gibraltar, that establish the survival of a population of Neanderthals to 28 kyr bp. These Neanderthals survived in the southernmost point of Europe, within a particular physiographic context, and are the last currently recorded anywhere. Our results show that the Neanderthals survived in isolated refuges well after the arrival of modern humans in Europe.