The LANL hemorrhagic fever virus database, a new platform for analyzing biothreat viruses

Hemorrhagic fever viruses (HFVs) are a diverse set of over 80 viral species, found in 10 different genera comprising five different families: arena-, bunya-, flavi-, filo- and togaviridae. All these viruses are highly variable and evolve rapidly, making them elusive targets for the immune system and for vaccine and drug design. About 55 000 HFV sequences exist in the public domain today. A central website that provides annotated sequences and analysis tools will be helpful to HFV researchers worldwide. The HFV sequence database collects and stores sequence data and provides a user-friendly search interface and a large number of sequence analysis tools, following the model of the highly regarded and widely used Los Alamos HIV database [Kuiken, C., B. Korber, and R.W. Shafer, HIV sequence databases. AIDS Rev, 2003. 5: p. 52–61]. The database uses an algorithm that aligns each sequence to a species-wide reference sequence. The NCBI RefSeq database [Sayers et al. (2011) Database resources of the National Center for Biotechnology Information. Nucleic Acids Res., 39, D38–D51.] is used for this; if a reference sequence is not available, a Blast search finds the best candidate. Using this method, sequences in each genus can be retrieved pre-aligned. The HFV website can be accessed via http://hfv.lanl.gov

What makes Individual I's a Collective We; Coordination mechanisms & costs

For a collective to become greater than the sum of its parts, individuals' efforts and activities must be coordinated or regulated. Not readily observable and measurable, this particular aspect often goes unnoticed and understudied in complex systems. Diving into the Wikipedia ecosystem, where people are free to join and voluntarily edit individual pages with no firm rules, we identified and quantified three fundamental coordination mechanisms and found they scale with an influx of contributors in a remarkably systemic way over three order of magnitudes. Firstly, we have found a super-linear growth in mutual adjustments (scaling exponent: 1.3), manifested through extensive discussions and activity reversals. Secondly, the increase in direct supervision (scaling exponent: 0.9), as represented by the administrators' activities, is disproportionately limited. Finally, the rate of rule enforcement exhibits the slowest escalation (scaling exponent 0.7), reflected by automated bots. The observed scaling exponents are notably robust across topical categories with minor variations attributed to the topic complication. Our findings suggest that as more people contribute to a project, a self-regulating ecosystem incurs faster mutual adjustments than direct supervision and rule enforcement. These findings have practical implications for online collaborative communities aiming to enhance their coordination efficiency. These results also have implications for how we understand human organizations in general.Comment: 27 pages, 7 figure

CATNAP: a tool to compile, analyze and tally neutralizing antibody panels

CATNAP (Compile, Analyze and Tally NAb Panels) is a new web server at Los Alamos HIV Database, created to respond to the newest advances in HIV neutralizing antibody research. It is a comprehensive platform focusing on neutralizing antibody potencies in conjunction with viral sequences. CATNAP integrates neutralization and sequence data from published studies, and allows users to analyze that data for each HIV Envelope protein sequence position and each antibody. The tool has multiple data retrieval and analysis options. As input, the user can pick specific antibodies and viruses, choose a panel from a published study, or supply their own data. The output superimposes neutralization panel data, virus epidemiological data, and viral protein sequence alignments on one page, and provides further information and analyses. The user can highlight alignment positions, or select antibody contact residues and view position-specific information from the HIV databases. The tool calculates tallies of amino acids and N-linked glycosylation motifs, counts of antibody-sensitive and -resistant viruses in conjunction with each amino acid or N-glycosylation motif, and performs Fisher's exact test to detect potential positive or negative amino acid associations for the selected antibody. Website name: CATNAP (Compile, Analyze and Tally NAb Panels). Website address: http://hiv.lanl.gov/catnap

Message assertiveness and price discount in prosocial advertising: differences between Americans and Koreans

Purpose Prosocial advertisers widely use assertive messages to encourage prosocial attitudes and behaviors, but ironically, assertive messages may cause reactance. By applying cultural theories and the reciprocity principle, this study aims to observe whether consumers’ responses to assertive messages hold across culturally different audiences (Americans vs South Koreans) and different consumption situations (price discount vs no discount). Design/methodology/approach American and Korean participants take part in three experimental studies examining the interactions of nationality, price discounts and assertive messaging for influencing consumer responses, first to a prosocial ad encouraging recycling (Study 1), the second for a campaign requesting donations for disadvantaged children (Study 2) and the third to prosocial messages encouraging water conservation (Study 3). Findings The three experiments strongly support the moderating role of price discounts and cultural backgrounds in the persuasiveness of assertive prosocial messages. American consumers generally dislike assertive messages, but feel reciprocal obligations if marketers include price discounts, whereas South Korean consumers accept both assertive and nonassertive messages without resistance, and discounts have no effects on persuasion. Research limitations/implications The findings make two key contributions to the literature and to prosocial advertising practices. First, although many corporations have adopted philanthropic strategies, few researchers have examined how specific consumption contexts determine the effectiveness of prosocial persuasion. The findings show how price discounts and message framing potentially alter the effectiveness of prosocial messages across Eastern and Western cultures. Second, assertive language evokes reactance, but the findings suggest that reactive responses to prosocial advertising are culture-specific. Practical implications International nonprofit organizations and brands using philanthropic strategies might use the guidelines of this study for tailoring strategic, practical prosocial messages that will appeal to consumers from diverse cultural backgrounds. In particular, pro-environmental and charity campaigns targeting North American or Western European populations may consider bundling discounts into promotions to evoke reciprocity. Originality/value Findings provide novel implications for social marketers regarding on how to couple message assertiveness and price discounts to maximize the success of prosocial messages in different cultures

Haploinsufficiency of human APOE reduces amyloid deposition in a mouse model of amyloid-β amyloidosis

Apolipoprotein E ε4 (APOE ε4) is the strongest genetic risk factor for Alzheimer’s disease (AD). Evidence suggests that the effect of apoE isoforms on amyloid-β (Aβ) accumulation in the brain plays a critical role in AD pathogenesis. Like in humans, apoE4 expression in animal models that develop Aβ-amyloidosis results in greater Aβ and amyloid deposition than with apoE3 expression. However, whether decreasing levels of apoE3 or apoE4 would promote or attenuate Aβ-related pathology has not been directly addressed. To determine the effect of decreasing human apoE levels on Aβ accumulation in vivo, we generated human APOE isoform haploinsufficient mouse models by crossing APPPS1-21 mice with APOE isoform knock-in mice. By genetically manipulating APOE gene dosage, we demonstrate that decreasing human apoE levels, regardless of isoform status, results in significantly decreased amyloid plaque deposition and microglial activation. This differences in amyloid load between apoE3 and apoE4 expressing mice were not due to apoE4 protein being present at lower levels than apoE3. These data suggest that current therapeutic strategies to increase apoE levels without altering its lipidation state may actually worsen Aβ amyloidosis, while increasing apoE degradation or inhibiting its synthesis may be a more effective treatment approach

Quaternary structures of Vac8 differentially regulate the Cvt and PMN pathways.

Armadillo (ARM) repeat proteins constitute a large protein family with diverse and fundamental functions in all organisms, and armadillo repeat domains share high structural similarity. However, exactly how these structurally similar proteins can mediate diverse functions remains a long-standing question. Vac8 (vacuole related 8) is a multifunctional protein that plays pivotal roles in various autophagic pathways, including piecemeal microautophagy of the nucleus (PMN) and cytoplasm-to-vacuole targeting (Cvt) pathways in the budding yeast Saccharomyces cerevisiae. Vac8 comprises an H1 helix at the N terminus, followed by 12 armadillo repeats. Herein, we report the crystal structure of Vac8 bound to Atg13, a key component of autophagic machinery. The 70-angstrom extended loop of Atg13 binds to the ARM domain of Vac8 in an antiparallel manner. Structural, biochemical, and in vivo experiments demonstrated that the H1 helix of Vac8 intramolecularly associates with the first ARM and regulates its self-association, which is crucial for Cvt and PMN pathways. The structure of H1 helix-deleted Vac8 complexed with Atg13 reveals that Vac8[Delta 19-33]-Atg13 forms a heterotetramer and adopts an extended superhelical structure exclusively employed in the Cvt pathway. Most importantly, comparison of Vac8-Nvj1 and Vac8-Atg13 provides a molecular understanding of how a single ARM domain protein adopts different quaternary structures depending on its associated proteins to differentially regulate 2 closely related but distinct cellular pathways

Magnetoelectric effects of nanoparticulate Pb(Zr0.52Ti0.48)O3-NiFe2O4 composite films

We fabricated Pb(Zr0.52Ti0.48)O3-NiFe2O4 composite films consisting of randomly dispersed NiFe2O4 nanoparticles in the Pb(Zr0.52Ti0.48)O3 matrix. The structural analysis revealed that the crystal axes of the NiFe2O4 nanoparticles are aligned with those of the ferroelectric matrix. The composite has good ferroelectric and magnetic properties. We measured the transverse and longitudinal components of the magnetoelectric voltage coefficient, which supports the postulate that the magnetoelectric effect comes from direct stress coupling between magnetostrictive NiFe2O4 and piezoelectric Pb(Zr0.52Ti0.48)O3 grains.Comment: 11 pages, 4 figure

A Case of Placenta Increta Presenting as Delayed Postabortal Intraperitoneal Bleeding in the First Trimester

Placenta increta is an uncommon and life-threatening complication of pregnancy characterized by complete or partial absence of the decidua basalis. Placenta increta usually presents with vaginal bleeding during difficult placental removal in the third-trimester. Although placenta increta may complicate first and early second-trimester pregnancy loss, the diagnosis can be very difficult during early pregnancy and thus the lesion is difficult to identify. We encountered with a woman who was diagnosed with placenta increta after receiving emergency hysterectomy due to intraperitoneal bleeding 2 months after an uncomplicated dilatation and curettage in the first trimester. Therefore, we report this case with a brief review of the literature