The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes

Sperm and eggs carry distinctive epigenetic modifications that are adjusted by reprogramming after fertilization. The paternal genome in a zygote undergoes active DNA demethylation before the first mitosis. The biological significance and mechanisms of this paternal epigenome remodelling have remained unclear. Here we report that, within mouse zygotes, oxidation of 5-methylcytosine (5mC) occurs on the paternal genome, changing 5mC into 5-hydroxymethylcytosine (5hmC). Furthermore, we demonstrate that the dioxygenase Tet3 (ref. 5) is enriched specifically in the male pronucleus. In Tet3-deficient zygotes from conditional knockout mice, paternal-genome conversion of 5mC into 5hmC fails to occur and the level of 5mC remains constant. Deficiency of Tet3 also impedes the demethylation process of the paternal Oct4 and Nanog genes and delays the subsequent activation of a paternally derived Oct4 transgene in early embryos. Female mice depleted of Tet3 in the germ line show severely reduced fecundity and their heterozygous mutant offspring lacking maternal Tet3 suffer an increased incidence of developmental failure. Oocytes lacking Tet3 also seem to have a reduced ability to reprogram the injected nuclei from somatic cells. Therefore, Tet3-mediated DNA hydroxylation is involved in epigenetic reprogramming of the zygotic paternal DNA following natural fertilization and may also contribute to somatic cell nuclear reprogramming during animal cloning.     

No upward trends in the occurrence of extreme floods in central Europe

Extreme river floods have been a substantial natural hazard in Europe over the past centuries, and radiative effects of recent anthropogenic changes in atmospheric composition are expected to cause climate changes, especially enhancement of the hydrological cycle, leading to an increased flood risk. For the past few decades, however, observations from Europe do not show a clear increase in flood occurrence rate. Here we present longer-term records of winter and summer floods in two of the largest rivers in central Europe, the Elbe and Oder rivers. For the past 80 to 150 yr, we find a decrease in winter flood occurrence in both rivers, while summer floods show no trend, consistent with trends in extreme precipitation occurrence. The reduction in winter flood occurrence can partly be attributed to fewer events of strong freezing-following such events, breaking river ice at the end of the winter may function as a water barrier and enhance floods severely. Additionally, we detect significant long-term changes in flood occurrence rates in the sixteenth to nineteenth centuries, and conclude that reductions in river length, construction of reservoirs and deforestation have had minor effects on flood frequency.     

Auxin inhibits endocytosis and promotes its own efflux from cells

One of the mechanisms by which signalling molecules regulate cellular behaviour is modulating subcellular protein translocation. This mode of regulation is often based on specialized vesicle trafficking, termed constitutive cycling, which consists of repeated internalization and recycling of proteins to and from the plasma membrane. No such mechanism of hormone action has been shown in plants although several proteins, including the PIN auxin efflux facilitators, exhibit constitutive cycling. Here we show that a major regulator of plant development, auxin, inhibits endocytosis. This effect is specific to biologically active auxins and requires activity of the Calossin-like protein BIG. By inhibiting the internalization step of PIN constitutive cycling, auxin increases levels of PINs at the plasma membrane. Concomitantly, auxin promotes its own efflux from cells by a vesicle-trafficking-dependent mechanism. Furthermore, asymmetric auxin translocation during gravitropism is correlated with decreased PIN internalization. Our data imply a previously undescribed mode of plant hormone action: by modulating PIN protein trafficking, auxin regulates PIN abundance and activity at the cell surface, providing a mechanism for the feedback regulation of auxin transport.     

Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways

Cystic renal diseases are caused by mutations of proteins that share a unique subcellular localization: the primary cilium of tubular epithelial cells. Mutations of the ciliary protein inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure. Here we report that inversin acts as a molecular switch between different Wnt signaling cascades. Inversin inhibits the canonical Wnt pathway by targeting cytoplasmic dishevelled (Dsh or Dvl1) for degradation; concomitantly, it is required for convergent extension movements in gastrulating Xenopus laevis embryos and elongation of animal cap explants, both regulated by noncanonical Wnt signaling. In zebrafish, the structurally related switch molecule diversin ameliorates renal cysts caused by the depletion of inversin, implying that an inhibition of canonical Wnt signaling is required for normal renal development. Fluid flow increases inversin levels in ciliated tubular epithelial cells and seems to regulate this crucial switch between Wnt signaling pathways during renal development.     

Monitoring of organochlorine pesticides in the urban air of Dalian,China with semipermeable membrane devices

The concentrations of 28 organochlorine pesti- cides （OCPs） in the urban air of Dalian, China were measured using semipermeable membrane devices （SPMDs） for the first time. Alpha-hexachlorocyclohexane （α-HCH）, β-HCH, pentachlorobenzene （PentCB）, hexachlorobenzene （HexCB）, 4,4＇-dichlorodiphenyltrichloroethane （4,4＇-DDT）, 4,4＇- dichlorodiphenyldichloroethene, endosulfan-I and endosul- fan-Ⅱ were the predominant OCPs in the urban air of Dalian. The concentration of OCPs sequestrated by SPMDs （CSPMD） ranged from undetected to 56,772 pg SPMD-1 and had a linear correlation with the reciprocal of the average ambient atmospheric temperature （1/T）. The CSPMD of PentCB and HexCB had negative correlations with T, whereas the other detected OCPs had a positive correlation. The source of HCHs, DDTs, HexCB, PentCB, chlordane, and endosulfan in the air were also evaluated. The OCPs in the urban air of Dalian could be attributed to the seasonal usage of pesticides,combustion, volatilization of aged OCPs from soil, water, plants, and long-range atmospheric transport.     

MAPK pathway activation in pilocytic astrocytoma

Pilocytic astrocytoma (PA) is the most common tumor of the pediatric central nervous system (CNS). A body of research over recent years has demonstrated a key role for mitogen-activated protein kinase (MAPK) pathway signaling in the development and behavior of PAs. Several mechanisms lead to activation of this pathway in PA, mostly in a mutually exclusive manner, with constitutive BRAF kinase activation subsequent to gene fusion being the most frequent. The high specificity of this fusion to PA when compared with other CNS tumors has diagnostic utility. In addition, the frequency of alteration of this key pathway provides an opportunity for molecularly targeted therapy in this tumor. Here, we review the current knowledge on mechanisms of MAPK activation in PA and some of the downstream consequences of this activation, which are now starting to be elucidated both in vitro and in vivo, as well as clinical considerations and possible future directions.     

Reconfigurable robot based on modular joint concept

0IntroductionWiththe rapid progress of the modern science andtechnology,the acquirement and usage of resources willbe extendedtothe spacefromthe earth.But many activi-ties can not be completed without space robots,such asthe construction and maintenance of the InternationalSpace Station(ISS),the release and retrieve of the satel-lite[1,2].Since space robot has been brought forward,upto date,the Canadarm2(SSRMS)is the only real-work-ingrobot manipulator[3].ETS-VII is the worldfirst satel…