Metagenomic and functional analysis of hindgut microbiota of a wood-feeding higher termite

From the standpoints of both basic research and biotechnology, there is considerable interest in reaching a clearer understanding of the diversity of biological mechanisms employed during lignocellulose degradation. Globally, termites are an extremely successful group of wood-degrading organisms and are therefore important both for their roles in carbon turnover in the environment and as potential sources of biochemical catalysts for efforts aimed at converting wood into biofuels. Only recently have data supported any direct role for the symbiotic bacteria in the gut of the termite in cellulose and xylan hydrolysis. Here we use a metagenomic analysis of the bacterial community resident in the hindgut paunch of a wood-feeding 'higher' Nasutitermes species (which do not contain cellulose-fermenting protozoa) to show the presence of a large, diverse set of bacterial genes for cellulose and xylan hydrolysis. Many of these genes were expressed in vivo or had cellulase activity in vitro, and further analyses implicate spirochete and fibrobacter species in gut lignocellulose degradation. New insights into other important symbiotic functions including H2 metabolism, CO2-reductive acetogenesis and N2 fixation are also provided by this first system-wide gene analysis of a microbial community specialized towards plant lignocellulose degradation. Our results underscore how complex even a 1-microl environment can be.     

Studies in nearctic desert sand dune Orthoptera. Part XV: Eremogeography of Spaniacris with bioecological notes

Four decades of the author's records indicate that Spaniacris deserticola (Bruner) is confined within the periphery of the Colorado Desert. It is usually found, near or within a few hundred feet of sea level, marking the shore line of ancient Lake Cahuilla (except for the Dale Lake record). The preferred host plant is Coldenia palmeri growing on the lower fringes of bajadas, with C. plicata on drift sand being second in preference. Spaniacris can tolerate sand and rock temperatures of 60 C. (believed to be a maximum for Colorado Desert life). Mating takes place at that and lower temperatures. When they are disturbed while on the tops of host plants, their flight is low and direct and of short duration, and they come to rest on the torrid soil for long periods of time. The female, much larger than the male, can sustain the male in flight while mating. The study verified spatial longevity of Spaniacris at Indio, California, after approximately 70 years and for the Kane Springs area after 52 years.     

EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus

Nipah virus (NiV) is an emergent paramyxovirus that causes fatal encephalitis in up to 70 percent of infected patients, and there is evidence of human-to-human transmission. Endothelial syncytia, comprised of multinucleated giant-endothelial cells, are frequently found in NiV infections, and are mediated by the fusion (F) and attachment (G) envelope glycoproteins. Identification of the receptor for this virus will shed light on the pathobiology of NiV infection, and spur the rational development of effective therapeutics. Here we report that ephrinB2, the membrane-bound ligand for the EphB class of receptor tyrosine kinases (RTKs), specifically binds to the attachment (G) glycoprotein of NiV. Soluble Fc-fusion proteins of ephrinB2, but not ephrinB1, effectively block NiV fusion and entry into permissive cell types. Moreover, transfection of ephrinB2 into non-permissive cells renders them permissive for NiV fusion and entry. EphrinB2 is expressed on endothelial cells and neurons, which is consistent with the known cellular tropism for NiV. Significantly, we find that NiV-envelope-mediated infection of microvascular endothelial cells and primary cortical rat neurons is inhibited by soluble ephrinB2, but not by the related ephrinB1 protein. Cumulatively, our data show that ephrinB2 is a functional receptor for NiV.     

Ectoparasites of the occult bat, Myotis occultus (Chiroptera: Vespertilionidae)

Only a single previous study has examined ectoparasites of the occult bat ( Myotis occultus ), from which only 2 species of fleas were identified. For our study, we examined 202 individuals, 52 fresh hosts and 150 museum specimens, from New Mexico and southern Colorado for ectoparasites. We recorded 2158 ectoparasites, 634 from fresh hosts and 1524 from museum specimens. Ectoparasites belonged to 10 families and 13 genera of insect or acari and represent new host and locality records. In general, ectoparasites collected from fresh hosts and museum specimens were represented by 4 major species of mite: Macronyssus crosbyi, Alabidocarpus calcaratus, Acanthophthirius lucifugus, and Alabidocarpus nr. eptesicus. From our study, we found fresh hosts to have significantly greater prevalence values for Myodopsylla gentilis (flea), Chiroptonyssus robustipes (mite), and Leptotrombidium myotis (chigger), whereas museum specimens had significantly greater prevalence values for A. calcaratus (mite) and A. nr. eptesicus (mite). There were no significant differences between prevalence values for 4 mites including M. crosbyi, A. lucifugus, Pteracarus nr. minutus, and Cryptonyssus sp. Our study represents the only extensive study of ectoparasites on M. occultus and provides evidence for the importance of examining fresh hosts and museum specimens in future ectoparasite studies.     

Human Culture and Science: Equality and Inequality as Foundations of Scientific Thought

We argue that the concepts of `human equality' and `inequality' play an important role in the structure of science and philosophy. When the value of `human inequality' predominates, scientific categories are formed in accordance with the principle of `hierarchical differentiation' and concepts remain closely tied to the objects they are referring to. Following Mirowski we define this as the `anthropometric stage' of human thought and development. Contrary, Mirowski's `syndetic stage' refers to societies where the value of `human equality' prevails. Here concepts appear that are universally applicable. However, because of their conventional nature these concepts cannot be `grasped' any longer by human intuition. Between the `anthropometric' and `syndetic' stages, a `lineamentric stage' appears, a period of transition from `human equality' to `human inequality'. Being both a bridge and gap between the two other stages, the `lineamentric' stage contains many contradictions between an `abstract attitude' and `concrete categories'. In this paper we examine the anthropometric, lineamentric and syndetic stages and discuss several examples taken from philosophy, logic, mathematics and physics.     

Molecular recycling within amyloid fibrils

Amyloid fibrils are thread-like protein aggregates with a core region formed from repetitive arrays of beta-sheets oriented parallel to the fibril axis. Such structures were first recognized in clinical disorders, but more recently have also been linked to a variety of non-pathogenic phenomena ranging from the transfer of genetic information to synaptic changes associated with memory. The observation that many proteins can convert into similar structures in vitro has suggested that this ability is a generic feature of polypeptide chains. Here we have probed the nature of the amyloid structure by monitoring hydrogen/deuterium exchange in fibrils formed from an SH3 domain using a combination of nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. The results reveal that under the conditions used in this study, exchange is dominated by a mechanism of dissociation and re-association that results in the recycling of molecules within the fibril population. This insight into the dynamic nature of amyloid fibrils, and the ability to determine the parameters that define this behaviour, have important implications for the design of therapeutic strategies directed against amyloid disease.     

X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity.

The ClC chloride channels catalyse the selective flow of Cl- ions across cell membranes, thereby regulating electrical excitation in skeletal muscle and the flow of salt and water across epithelial barriers. Genetic defects in ClC Cl- channels underlie several familial muscle and kidney diseases. Here we present the X-ray structures of two prokaryotic ClC Cl- channels from Salmonella enterica serovar typhimurium and Escherichia coli at 3.0 and 3.5 A, respectively. Both structures reveal two identical pores, each pore being formed by a separate subunit contained within a homodimeric membrane protein. Individual subunits are composed of two roughly repeated halves that span the membrane with opposite orientations. This antiparallel architecture defines a selectivity filter in which a Cl- ion is stabilized by electrostatic interactions with alpha-helix dipoles and by chemical coordination with nitrogen atoms and hydroxyl groups. These findings provide a structural basis for further understanding the function of ClC Cl- channels, and establish the physical and chemical basis of their anion selectivity.     

Preseismic velocity changes observed from active source monitoring at the Parkfield SAFOD drill site

Measuring stress changes within seismically active fault zones has been a long-sought goal of seismology. One approach is to exploit the stress dependence of seismic wave velocity, and we have investigated this in an active source cross-well experiment at the San Andreas Fault Observatory at Depth (SAFOD) drill site. Here we show that stress changes are indeed measurable using this technique. Over a two-month period, we observed an excellent anti-correlation between changes in the time required for a shear wave to travel through the rock along a fixed pathway (a few microseconds) and variations in barometric pressure. We also observed two large excursions in the travel-time data that are coincident with two earthquakes that are among those predicted to produce the largest coseismic stress changes at SAFOD. The two excursions started approximately 10 and 2 hours before the events, respectively, suggesting that they may be related to pre-rupture stress induced changes in crack properties, as observed in early laboratory studies.     

Histone H2AX-dependent GABA(A) receptor regulation of stem cell proliferation

Stem cell self-renewal implies proliferation under continued maintenance of multipotency. Small changes in numbers of stem cells may lead to large differences in differentiated cell numbers, resulting in significant physiological consequences. Proliferation is typically regulated in the G1 phase, which is associated with differentiation and cell cycle arrest. However, embryonic stem (ES) cells may lack a G1 checkpoint. Regulation of proliferation in the 'DNA damage' S/G2 cell cycle checkpoint pathway is known for its role in the maintenance of chromatin structural integrity. Here we show that autocrine/paracrine gamma-aminobutyric acid (GABA) signalling by means of GABA(A) receptors negatively controls ES cell and peripheral neural crest stem (NCS) cell proliferation, preimplantation embryonic growth and proliferation in the boundary-cap stem cell niche, resulting in an attenuation of neuronal progenies from this stem cell niche. Activation of GABA(A) receptors leads to hyperpolarization, increased cell volume and accumulation of stem cells in S phase, thereby causing a rapid decrease in cell proliferation. GABA(A) receptors signal through S-phase checkpoint kinases of the phosphatidylinositol-3-OH kinase-related kinase family and the histone variant H2AX. This signalling pathway critically regulates proliferation independently of differentiation, apoptosis and overt damage to DNA. These results indicate the presence of a fundamentally different mechanism of proliferation control in these stem cells, in comparison with most somatic cells, involving proteins in the DNA damage checkpoint pathway.     

Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9

Specific modifications to histones are essential epigenetic markers---heritable changes in gene expression that do not affect the DNA sequence. Methylation of lysine 9 in histone H3 is recognized by heterochromatin protein 1 (HP1), which directs the binding of other proteins to control chromatin structure and gene expression. Here we show that HP1 uses an induced-fit mechanism for recognition of this modification, as revealed by the structure of its chromodomain bound to a histone H3 peptide dimethylated at Nzeta of lysine 9. The binding pocket for the N-methyl groups is provided by three aromatic side chains, Tyr21, Trp42 and Phe45, which reside in two regions that become ordered on binding of the peptide. The side chain of Lys9 is almost fully extended and surrounded by residues that are conserved in many other chromodomains. The QTAR peptide sequence preceding Lys9 makes most of the additional interactions with the chromodomain, with HP1 residues Val23, Leu40, Trp42, Leu58 and Cys60 appearing to be a major determinant of specificity by binding the key buried Ala7. These findings predict which other chromodomains will bind methylated proteins and suggest a motif that they recognize.