Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy.

Soluble guanylate cyclase (sGC) is the primary receptor for nitric oxide (NO) in mammalian nitric oxide signaling. We determined structures of full-length Manduca sexta sGC in both inactive and active states using cryo-electron microscopy. NO and the sGC-specific stimulator YC-1 induce a 71° rotation of the heme-binding β H-NOX and PAS domains. Repositioning of the β H-NOX domain leads to a straightening of the coiled-coil domains, which, in turn, use the motion to move the catalytic domains into an active conformation. YC-1 binds directly between the β H-NOX domain and the two CC domains. The structural elongation of the particle observed in cryo-EM was corroborated in solution using small angle X-ray scattering (SAXS). These structures delineate the endpoints of the allosteric transition responsible for the major cyclic GMP-dependent physiological effects of NO

Human endogenous retrovirus K106 (HERV-K106) was infectious after the emergence of anatomically modern humans.

HERV-K113 and HERV-K115 have been considered to be among the youngest HERVs because they are the only known full-length proviruses that are insertionally polymorphic and maintain the open reading frames of their coding genes. However, recent data suggest that HERV-K113 is at least 800,000 years old, and HERV-K115 even older. A systematic study of HERV-K HML2 members to identify HERVs that may have infected the human genome in the more recent evolutionary past is lacking. Therefore, we sought to determine how recently HERVs were exogenous and infectious by examining sequence variation in the long terminal repeat (LTR) regions of all full-length HERV-K loci. We used the traditional method of inter-LTR comparison to analyze all full length HERV-Ks and determined that two insertions, HERV-K106 and HERV-K116 have no differences between their 5' and 3' LTR sequences, suggesting that these insertions were endogenized in the recent evolutionary past. Among these insertions with no sequence differences between their LTR regions, HERV-K106 had the most intact viral sequence structure. Coalescent analysis of HERV-K106 3' LTR sequences representing 51 ethnically diverse individuals suggests that HERV-K106 integrated into the human germ line approximately 150,000 years ago, after the emergence of anatomically modern humans

Moisture adsorption and desorption behavior of raw materials for the t-rtm process

The use of fiber reinforced plastics (FRPs) has significant potential to reduce the weight of components. As regards the sustainability of these components, thermoplastic matrices offer more potential for recycling than thermoset ones. A possible manufacturing process for the production of thermoplastic FRPs is thermoplastic resin transfer molding (T-RTM). In this very moisture-sensitive process, ε-caprolactam in addition to an activator and catalyst polymerizes anionically to polyamide 6 (aPA6). The anionic polymerization of aPA6 is slowed down or even completely blocked by the presence of water. This study analyses the sorption behavior of the matrix, fiber, binder and core materials for the production of anionic polyamide 6 composites, which are processed in the thermoplastic RTM process. Water vapor sorption measurements are used to determine the adsorption and desorption behavior of the materials. The maximum moisture loading of the materials provides information about the water adsorption capacity of the material. This knowledge is crucial for correct handling of the materials to achieve a fast process and good properties of the final product

Type I D-branes in an H-flux and twisted KO-theory

Witten has argued that charges of Type I D-branes in the presence of an H-flux, take values in twisted KO-theory. We begin with the study of real bundle gerbes and their holonomy. We then introduce the notion of real bundle gerbe KO-theory which we establish is a geometric realization of twisted KO-theory. We examine the relation with twisted K-theory, the Chern character and provide some examples. We conclude with some open problems.Comment: 23 pages, Latex2e, 2 new references adde

Loss of the <i>Arabidopsis thaliana</i> P4-ATPases ALA6 and ALA7 impairs pollen fitness and alters the pollen tube plasma membrane

Members of the P4 subfamily of P-type ATPases are thought to create and maintain lipid asymmetry in biological membranes by flipping specific lipids between membrane leaflets. In Arabidopsis, 7 of the 12 Aminophospholipid ATPase (ALA) family members are expressed in pollen. Here we show that double knockout of ALA6 and ALA7 (ala6/7) results in siliques with a ~2-fold reduction in seed set with a high frequency of empty seed positions near the bottom. Seed set was reduced to near zero when plants were grown under a hot/cold temperature stress. Reciprocal crosses indicate that the ala6/7 reproductive deficiencies are due to a defect related to pollen transmission. In-vitro growth assays provide evidence that that ala6/7 pollen tubes are short and slow, with ~2-fold reductions in both maximal growth rate and overall length relative to wild-type. Outcrosses show that when ala6/7 pollen are in competition with wild-type pollen, they have a near 0% success rate in fertilizing ovules near the bottom of the pistil, consistent with ala6/7 pollen having short and slow growth defects. The ala6/7 phenotypes were rescued by the expression of either an ALA6-YFP or GFP-ALA6 fusion protein, which showed localization to both the plasma membrane and highly-mobile endomembrane structures. A mass spectrometry analysis of mature pollen grains revealed significant differences between ala6/7 and wild-type, both in the relative abundance of lipid classes and in the average number of double bonds present in acyl side chains. A change in the properties of the ala6/7 plasma membrane was also indicated by a ~10-fold reduction of labeling by lipophilic FM-dyes relative to wild-type. Together, these results indicate that ALA6 and ALA7 provide redundant activities that function to directly or indirectly change the distribution and abundance lipids in pollen, and support a model in which ALA6 and ALA7 are critical for pollen fitness under normal and temperature-stress conditions

Human Endogenous Retrovirus K106 (HERV-K106) Was Infectious after the Emergence of Anatomically Modern Humans

HERV-K113 and HERV-K115 have been considered to be among the youngest HERVs because they are the only known full-length proviruses that are insertionally polymorphic and maintain the open reading frames of their coding genes. However, recent data suggest that HERV-K113 is at least 800,000 years old, and HERV-K115 even older. A systematic study of HERV-K HML2 members to identify HERVs that may have infected the human genome in the more recent evolutionary past is lacking. Therefore, we sought to determine how recently HERVs were exogenous and infectious by examining sequence variation in the long terminal repeat (LTR) regions of all full-length HERV-K loci. We used the traditional method of inter-LTR comparison to analyze all full length HERV-Ks and determined that two insertions, HERV-K106 and HERV-K116 have no differences between their 5′ and 3′ LTR sequences, suggesting that these insertions were endogenized in the recent evolutionary past. Among these insertions with no sequence differences between their LTR regions, HERV-K106 had the most intact viral sequence structure. Coalescent analysis of HERV-K106 3′ LTR sequences representing 51 ethnically diverse individuals suggests that HERV-K106 integrated into the human germ line approximately 150,000 years ago, after the emergence of anatomically modern humans.</p

Societal Adaptation to Decadal Climate Variability in the United States

The search for evidence of decadal climatic variability (DCV) has a very long history. In the past decade, a research community has coalesced around a series of roughly biennial workshops that have emphasized description of past DCV events; their causes and their teleconnections responsible for droughts, floods, and warm and cold spells around the world; and recently, the predictability of DCV events. Researchers studying climate change put great emphasis on prospective impacts, but the DCV community has yet to do so. To begin rectifying this deficiency, a short but ambitious workshop was convened in Waikoloa, near Kona, Hawaii, from 26-28 April 2007. This workshop, sponsored by the Center for Research on the Changing Earth System (CRCES), NOAA, the U.S. Geological Survey, and the U.S. Army Corps of Engineers, brought together climatologists and sectoral specialists representing agriculture, water resources, economics, the insurance industry, and developing country interests

Just how difficult can it be counting up R&D funding for emerging technologies (and is tech mining with proxy measures going to be any better?)

Decision makers considering policy or strategy related to the development of emerging technologies expect high quality data on the support for different technological options. A natural starting point would be R&D funding statistics. This paper explores the limitations of such aggregated data in relation to the substance and quantification of funding for emerging technologies. Using biotechnology as an illustrative case, we test the utility of a novel taxonomy to demonstrate the endemic weaknesses in the availability and quality of data from public and private sources. Using the same taxonomy, we consider the extent to which tech-mining presents an alternative, or potentially complementary, way to determine support for emerging technologies using proxy measures such as patents and scientific publications