Structures of complement component C3 provide insights into the function and evolution of immunity

The mammalian complement system is a phylogenetically ancient cascade system that has a major role in innate and adaptive immunity. Activation of component C3 (1,641 residues) is central to the three complement pathways and results in inflammation and elimination of self and non-self targets. Here we present crystal structures of native C3 and its final major proteolytic fragment C3c. The structures reveal thirteen domains, nine of which were unpredicted, and suggest that the proteins of the alpha2-macroglobulin family evolved from a core of eight homologous domains. A double mechanism prevents hydrolysis of the thioester group, essential for covalent attachment of activated C3 to target surfaces. Marked conformational changes in the alpha-chain, including movement of a critical interaction site through a ring formed by the domains of the beta-chain, indicate an unprecedented, conformation-dependent mechanism of activation, regulation and biological function of C3.     

Degree-based moment estimation for ordered networks

The edges between vertices in networks take not only the common binary values, but also the ordered values in some situations (e.g., the measurement of the relationship between people from worst to best in social networks). In this paper, the authors study the asymptotic property of the moment estimator based on the degrees of vertices in ordered networks whose edges are ordered random variables. In particular, the authors establish the uniform consistency and the asymptotic normality of the moment estimator when the number of parameters goes to infinity. Simulations and a real data example are provided to illustrate asymptotic results.     

Genetic diversity of rhizobial populations recovered from three Lotus species cultivated in the infra-arid Tunisian soils

gments from each strain based on the UPGMA algorithm from the combined patterns showed that Lotus isolates are very diverse and that they were affiliated to Sinorhizobium,Rhizobium,and Mesorhizobium genera.     

Age and Sex Distribution of Patients with Vasovagal Syncope Undergoing Head-up Tilt Table Test: 7-Year Audit

To investigate age and sex distribution of vasovagal syncope (VVS) patients undergoing head-up tilt table test (HUTT) at a tertiary hospital. The details of syncope patients who underwent HUTT at our department of cardiac function from January 2004 to December 2010 were reviewed. Of the 1 799 patients who underwent the HUTT, 854 tested positive, of which 558 (65.3%) were women, which were more than the women in the negative group (450, 47.6%) (p<0.05). VVS patients showed a bimodal age distribution between 11 and 20 years of age and in the fourth decade. In almost all age groups, mixed response was the highest compared with vasodepressor and cardioinhibitory. VVS patients who underwent HUTT indicate bimodal distribution peaking before the second decade and the fourth decade. The incidence of females was twice that of males before the sixth decade, and old age occupies a small percentage of VVS with no other comorbidities.     

Nesomyrmex micheleae,a new ant species (Hymenoptera: Formicidae) from the Dhofar Governorate,Oman, with a synoptic list,distribution map and key to the Arabian Nesomyrmex

ABSTRACT

A new species of the myrmicine ant genus Nesomyrmex Wheeler, 1910, N. micheleae Sharaf sp. nov., is described and illustrated from Oman based on the worker caste. The new species is a member of the N. angulatus species group and can be diagnosed by the golden yellow gaster that contrasts with the dark brown body; the irregular longitudinal rugulose sculpture on the cephalic surface; and the finely punctate mesonotum and propodeal dorsum. A synoptic species list, an updated key and a distribution map to the Arabian Nesomyrmex species are presented. Continued ant species discoveries are central to large-scale diversity patterns, conservation biology and macroecology.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:FBCEACA7-E543-4B10-AB9D-D63319DCB31F http://www.zoobank.org/urn:lsid:zoobank.org:act:1D2EC498-3B2E-43CD-A3C0-1C6C237471E2     

Optimal prediction with nonstationary ARFIMA model

We propose two methods to predict nonstationary long‐memory time series. In the first one we estimate the long‐range dependent parameter d by using tapered data; we then take the nonstationary fractional filter to obtain stationary and short‐memory time series. In the second method, we take successive differences to obtain a stationary but possibly long‐memory time series. For the two methods the forecasts are based on those obtained from the stationary components. Copyright © 2007 John Wiley & Sons, Ltd.     

Non-canonical inflammasome activation targets caspase-11

Caspase-1 activation by inflammasome scaffolds comprised of intracellular nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and the adaptor ASC is believed to be essential for production of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 during the innate immune response. Here we show, with C57BL/6 Casp11 gene-targeted mice, that caspase-11 (also known as caspase-4) is critical for caspase-1 activation and IL-1β production in macrophages infected with Escherichia coli, Citrobacter rodentium or Vibrio cholerae. Strain 129 mice, like Casp11(-/-) mice, exhibited defects in IL-1β production and harboured a mutation in the Casp11 locus that attenuated caspase-11 expression. This finding is important because published targeting of the Casp1 gene was done using strain 129 embryonic stem cells. Casp1 and Casp11 are too close in the genome to be segregated by recombination; consequently, the published Casp1(-/-) mice lack both caspase-11 and caspase-1. Interestingly, Casp11(-/-) macrophages secreted IL-1β normally in response to ATP and monosodium urate, indicating that caspase-11 is engaged by a non-canonical inflammasome. Casp1(-/-)Casp11(129mt/129mt) macrophages expressing caspase-11 from a C57BL/6 bacterial artificial chromosome transgene failed to secrete IL-1β regardless of stimulus, confirming an essential role for caspase-1 in IL-1β production. Caspase-11 rather than caspase-1, however, was required for non-canonical inflammasome-triggered macrophage cell death, indicating that caspase-11 orchestrates both caspase-1-dependent and -independent outputs. Caspase-1 activation by non-canonical stimuli required NLRP3 and ASC, but caspase-11 processing and cell death did not, implying that there is a distinct activator of caspase-11. Lastly, loss of caspase-11 rather than caspase-1 protected mice from a lethal dose of lipopolysaccharide. These data highlight a unique pro-inflammatory role for caspase-11 in the innate immune response to clinically significant bacterial infections.     

Solid-liquid iron partitioning in Earth's deep mantle

Melting processes in the deep mantle have important implications for the origin of the deep-derived plumes believed to feed hotspot volcanoes such as those in Hawaii. They also provide insight into how the mantle has evolved, geochemically and dynamically, since the formation of Earth. Melt production in the shallow mantle is quite well understood, but deeper melting near the core-mantle boundary remains controversial. Modelling the dynamic behaviour of deep, partially molten mantle requires knowledge of the density contrast between solid and melt fractions. Although both positive and negative melt buoyancies can produce major chemical segregation between different geochemical reservoirs, each type of buoyancy yields drastically different geodynamical models. Ascent or descent of liquids in a partially molten deep mantle should contribute to surface volcanism or production of a deep magma ocean, respectively. We investigated phase relations in a partially molten chondritic-type material under deep-mantle conditions. Here we show that the iron partition coefficient between aluminium-bearing (Mg,Fe)SiO(3) perovskite and liquid is between 0.45 and 0.6, so iron is not as incompatible with deep-mantle minerals as has been reported previously. Calculated solid and melt density contrasts suggest that melt generated at the core-mantle boundary should be buoyant, and hence should segregate upwards. In the framework of the magma oceans induced by large meteoritic impacts on early Earth, our results imply that the magma crystallization should push the liquids towards the surface and form a deep solid residue depleted in incompatible elements.     

Oligodendroglia metabolically support axons and contribute to neurodegeneration

Oligodendroglia support axon survival and function through mechanisms independent of myelination, and their dysfunction leads to axon degeneration in several diseases. The cause of this degeneration has not been determined, but lack of energy metabolites such as glucose or lactate has been proposed. Lactate is transported exclusively by monocarboxylate transporters, and changes to these transporters alter lactate production and use. Here we show that the most abundant lactate transporter in the central nervous system, monocarboxylate transporter 1 (MCT1, also known as SLC16A1), is highly enriched within oligodendroglia and that disruption of this transporter produces axon damage and neuron loss in animal and cell culture models. In addition, this same transporter is reduced in patients with, and in mouse models of, amyotrophic lateral sclerosis, suggesting a role for oligodendroglial MCT1 in pathogenesis. The role of oligodendroglia in axon function and neuron survival has been elusive; this study defines a new fundamental mechanism by which oligodendroglia support neurons and axons.