A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

Porosity estimation of (Moso bamboo) by computed tomography and backscattered electron imaging

This study aims to investigate and quantify the porosity in the cross section of Phyllostachys edulis (Moso bamboo) culm wall. The porosity results are expected to be utilised in numerical study of heat and moisture transfer. Computed tomography (CT) and backscattered electron (BSE) imaging methods are utilised in this study because these two methods allow measurements of the anisotropic features of bamboo specimens. The results of these two methods can be represented as the function of the real dimension rather than the pore size distribution of the specimen. The specimens are obtained from eight different locations along the Moso bamboo culms. Both internodes and nodes specimens are measured in this study. The average porosity, standard deviation (SD) and coefficient of variation (COV) are calculated for BSE and CT results. Pearson product-moment correlation coefficient (PPMCC) is also calculated in this study to analyse the correlation between the BSE results and CT results. Typical porosity results from 400 sampling points and 10 portions average porosity are analysed in this study. The CT scanning results show similar trend with BSE results. The correlation relationship between BSE and CT results approaches moderate correlation level to strong correlation level. The average porosity of internode specimens is from 43.9 to 58.8 % by BSE measurement and from 44.9 to 63.4 % by CT measurement. The average porosity of node specimens is from 37.4 to 56.6 % by BSE measurement and from 32.1 to 62.2 % by CT measurement

Porosity estimation of Phyllostachys edulis (Moso bamboo) by computed tomography and backscattered electron imaging

This study aims to investigate and quantify the porosity in the cross section of Phyllostachys edulis (Moso bamboo) culm wall. The porosity results are expected to be utilised in numerical study of heat and moisture transfer. Computed tomography (CT) and backscattered electron (BSE) imaging methods are utilised in this study because these two methods allow measurements of the anisotropic features of bamboo specimens. The results of these two methods can be represented as the function of the real dimension rather than the pore size distribution of the specimen. The specimens are obtained from eight different locations along the Moso bamboo culms. Both internodes and nodes specimens are measured in this study. The average porosity, standard deviation (SD) and coefficient of variation (COV) are calculated for BSE and CT results. Pearson product-moment correlation coefficient (PPMCC) is also calculated in this study to analyse the correlation between the BSE results and CT results. Typical porosity results from 400 sampling points and 10 portions average porosity are analysed in this study. The CT scanning results show similar trend with BSE results. The correlation relationship between BSE and CT results approaches moderate correlation level to strong correlation level. The average porosity of internode specimens is from 43.9 to 58.8 % by BSE measurement and from 44.9 to 63.4 % by CT measurement. The average porosity of node specimens is from 37.4 to 56.6 % by BSE measurement and from 32.1 to 62.2 % by CT measurement

Hydrophobic and metallophobic surfaces: Highly stable non-wetting inorganic surfaces based on lanthanum phosphate nanorods

Metal oxides, in general, are known to exhibit significant wettability towards water molecules because of the high feasibility of synergetic hydrogen-bonding interactions possible at the solid-water interface. Here we show that the nano sized phosphates of rare earth materials (Rare Earth Phosphates, REPs), LaPO 4 in particular, exhibit without any chemical modification, unique combination of intrinsic properties including remarkable hydrophobicity that could be retained even after exposure to extreme temperatures and harsh hydrothermal conditions. Transparent nanocoatings of LaPO 4 as well as mixture of other REPs on glass surfaces are shown to display notable hydrophobicity with water contact angle (WCA) value of 120° while sintered and polished monoliths manifested WCA greater than 105°. Significantly, these materials in the form of coatings and monoliths also exhibit complete non-wettability and inertness towards molten metals like Ag, Zn, and Al well above their melting points. These properties, coupled with their excellent chemical and thermal stability, ease of processing, machinability and their versatile photo-physical and emission properties, render LaPO 4 and other REP ceramics utility in diverse applications

Gene Ontology: Pitfalls, Biases, and Remedies.

The Gene Ontology (GO) is a formidable resource, but there are several considerations about it that are essential to understand the data and interpret it correctly. The GO is sufficiently simple that it can be used without deep understanding of its structure or how it is developed, which is both a strength and a weakness. In this chapter, we discuss some common misinterpretations of the ontology and the annotations. A better understanding of the pitfalls and the biases in the GO should help users make the most of this very rich resource. We also review some of the misconceptions and misleading assumptions commonly made about GO, including the effect of data incompleteness, the importance of annotation qualifiers, and the transitivity or lack thereof associated with different ontology relations. We also discuss several biases that can confound aggregate analyses such as gene enrichment analyses. For each of these pitfalls and biases, we suggest remedies and best practices

Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC

The mesenchymal stroma harbors an important population of cells that possess stem cell-like characteristics including self renewal and differentiation capacities and can be derived from a variety of different sources. These multipotent mesenchymal stem cells (MSC) can be found in nearly all tissues and are mostly located in perivascular niches. MSC have migratory abilities and can secrete protective factors and act as a primary matrix for tissue regeneration during inflammation, tissue injuries and certain cancers

Presenilin Controls CBP Levels in the Adult Drosophila Central Nervous System

Background: Dominant mutations in both human Presenilin (Psn) genes have been correlated with the formation of amyloid plaques and development of familial early-onset Alzheimer’s disease (AD). However, a definitive mechanism whereby plaque formation causes the pathology of familial and sporadic forms of AD has remained elusive. Recent discoveries of several substrates for Psn protease activity have sparked alternative hypotheses for the pathophysiology underlying AD. CBP (CREB-binding protein) is a haplo-insufficient transcriptional co-activator with histone acetly-transferase (HAT) activity that has been proposed to be a downstream target of Psn signaling. Individuals with altered CBP have cognitive deficits that have been linked to several neurological disorders. Methodology/Principal Findings: Using a transgenic RNA-interference strategy to selectively silence CBP, Psn, and Notch in adult Drosophila, we provide evidence for the first time that Psn is required for normal CBP levels and for maintaining specific global acetylations at lysine 8 of histone 4 (H4K8ac) in the central nervous system (CNS). In addition, flies conditionally compromised for the adult-expression of CBP display an altered geotaxis behavior that may reflect a neurological defect. Conclusions/Significance: Our data support a model in which Psn regulates CBP levels in the adult fly brain in a manner that is independent of Notch signaling. Although we do not understand the molecular mechanism underlying th

The Complete Genome Sequence of ‘Candidatus Liberibacter solanacearum’, the Bacterium Associated with Potato Zebra Chip Disease

Zebra Chip (ZC) is an emerging plant disease that causes aboveground decline of potato shoots and generally results in unusable tubers. This disease has led to multi-million dollar losses for growers in the central and western United States over the past decade and impacts the livelihood of potato farmers in Mexico and New Zealand. ZC is associated with ‘Candidatus Liberibacter solanacearum’, a fastidious alpha-proteobacterium that is transmitted by a phloem-feeding psyllid vector, Bactericera cockerelli Sulc. Research on this disease has been hampered by a lack of robust culture methods and paucity of genome sequence information for ‘Ca. L. solanacearum’. Here we present the sequence of the 1.26 Mbp metagenome of ‘Ca. L. solanacearum’, based on DNA isolated from potato psyllids. The coding inventory of the ‘Ca. L. solanacearum’ genome was analyzed and compared to related Rhizobiaceae to better understand ‘Ca. L. solanacearum’ physiology and identify potential targets to develop improved treatment strategies. This analysis revealed a number of unique transporters and pathways, all potentially contributing to ZC pathogenesis. Some of these factors may have been acquired through horizontal gene transfer. Taxonomically, ‘Ca. L. solanacearum’ is related to ‘Ca. L. asiaticus’, a suspected causative agent of citrus huanglongbing, yet many genome rearrangements and several gene gains/losses are evident when comparing these two Liberibacter. species. Relative to ‘Ca. L. asiaticus’, ‘Ca. L. solanacearum’ probably has reduced capacity for nucleic acid modification, increased amino acid and vitamin biosynthesis functionalities, and gained a high-affinity iron transport system characteristic of several pathogenic microbes