Generational Differences in Faculty and Student Comfort with Technology Use

Background: Navigating through online education courses continues to be a struggle for some nursing students. At the same time, integrating technology into online courses can be difficult for nursing faculty. Purpose: The purpose of this study was to assess faculty technology integration practices, student attitudes about technology use, and generational differences related to faculty and student technology use. Methods: A descriptive cross-sectional survey design was used to obtain data for this study. Results: Integration of technology into online courses and student attitudes about technology use were not significantly different by generation. Faculty and students from the Baby Boomer and Generation X reported less comfort using technology and higher levels of anxiety using technology than did individuals from Generation Y. Conclusion: Significant generational variations were not noted in relation to technology integration into courses and overall student attitudes about technology in this study, but differences were noted in relation to comfort with use of technology and anxiety when using technology. Student learning outcomes and satisfaction with learning may be influenced by the student\u27s comfort using technology and faculty\u27s confidence in integrating and using technology to provide online instruction

Human Cytomegalovirus UL18 Utilizes US6 for Evading the NK and T-Cell Responses

Human cytomegalovirus (HCMV) US6 glycoprotein inhibits TAP function, resulting in down-regulation of MHC class I molecules at the cell surface. Cells lacking MHC class I molecules are susceptible to NK cell lysis. HCMV expresses UL18, a MHC class I homolog that functions as a surrogate to prevent host cell lysis. Despite a high level of sequence and structural homology between UL18 and MHC class I molecules, surface expression of MHC class I, but not UL18, is down regulated by US6. Here, we describe a mechanism of action by which HCMV UL18 avoids attack by the self-derived TAP inhibitor US6. UL18 abrogates US6 inhibition of ATP binding by TAP and, thereby, restores TAP-mediated peptide translocation. In addition, UL18 together with US6 interferes with the physical association between MHC class I molecules and TAP that is required for optimal peptide loading. Thus, regardless of the recovery of TAP function, surface expression of MHC class I molecules remains decreased. UL18 represents a unique immune evasion protein that has evolved to evade both the NK and the T cell immune responses

Shift in epitope dominance of IgM and IgG responses to Plasmodium falciparum MSP1 block 4

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum </it>merozoite surface protein-1 (MSP1) has been extensively studied as a blood-stage malaria vaccine candidate, with most work focused on the conserved 19 kDa and semi-conserved 42 kDa C-terminal regions (blocks 16-17) and the hypervariable N-terminal repeat region (block 2). However, recent genotyping studies suggest that additional regions of MSP1 may be under selective pressure, including a locus of intragenic recombination designated as block 4 within the 3' region of the gene.</p> <p>Methods</p> <p>The current study examined the antibody response to the two parental and two recombinant forms of block 4 and to blocks 16-17 (3D7) in study populations from Colombia, Papua New Guinea and Cameroon that differ in malaria transmission intensity and ethnic composition.</p> <p>Results</p> <p>IgM and IgG antibodies were detected against parental and recombinant MSP1 block 4 peptides in all three populations. Overall, 32-44% of the individuals produced IgM to one or more of the peptides, with most individuals having IgM antibodies reactive with both parental and recombinant forms. In contrast, IgG seropositivity to block 4 varied among populations (range 15-65%), with the majority of antibodies showing specificity for one or a pair of block 4 peptides. The IgG response to block 4 was significantly lower than that to blocks 16-17, indicating block 4 is subdominant. Antibodies to block 4 and blocks 16-17 displayed distinct IgG subclass biases, with block 4 responses biased toward IgG3 and blocks 16-17 toward IgG1. These patterns of responsiveness were consistently observed in the three study populations.</p> <p>Conclusions</p> <p>Production of antibodies specific for each parental and recombinant MSP1 block 4 allele in different populations exposed to <it>P. falciparum </it>is consistent with balancing selection of the MSP1 block 4 region by the immune response of individuals in areas of both low and high malaria transmission. MSP1 block 4 determinants may be important in isolate-specific immunity to <it>P. falciparum</it>.</p

Fault-controlled hydration of the upper mantle during continental rifting

Water and carbon are transferred from the ocean to the mantle in a process that alters mantle peridotite to create serpentinite and supports diverse ecosystems1. Serpentinized mantle rocks are found beneath the sea floor at slow- to ultraslow-spreading mid-ocean ridges1 and are thought to be present at about half the world’s rifted margins2, 3. Serpentinite is also inferred to exist in the downgoing plate at subduction zones4, where it may trigger arc magmatism or hydrate the deep Earth. Water is thought to reach the mantle via active faults3, 4. Here we show that serpentinization at the rifted continental margin offshore from western Spain was probably initiated when the whole crust cooled to become brittle and deformation was focused along large normal faults. We use seismic tomography to image the three-dimensional distribution of serpentinization in the mantle and find that the local volume of serpentinite beneath thinned, brittle crust is related to the amount of displacement along each fault. This implies that sea water reaches the mantle only when the faults are active. We estimate the fluid flux along the faults and find it is comparable to that inferred for mid-ocean ridge hydrothermal systems. We conclude that brittle processes in the crust may ultimately control the global flux of sea water into the Earth

The FAT10- and ubiquitin-dependent degradation machineries exhibit common and distinct requirements for MHC class I antigen presentation

Like ubiquitin (Ub), the ubiquitin-like protein FAT10 can serve as a signal for proteasome-dependent protein degradation. Here, we investigated the contribution of FAT10 substrate modification to MHC class I antigen presentation. We show that N-terminal modification of the human cytomegalovirus-derived pp65 antigen to FAT10 facilitates direct presentation and dendritic cell-mediated cross-presentation of the HLA-A2 restricted pp65495–503 epitope. Interestingly, our data indicate that the pp65 presentation initiated by either FAT10 or Ub partially relied on the 19S proteasome subunit Rpn10 (S5a). However, FAT10 distinguished itself from Ub in that it promoted a pp65 response which was not influenced by immunoproteasomes or PA28. Further divergence occurred at the level of Ub-binding proteins with NUB1 supporting the pp65 presentation arising from FAT10, while it exerted no effect on that initiated by Ub. Collectively, our data establish FAT10 modification as a distinct and alternative signal for facilitated MHC class I antigen presentation

Phase 1 Study of a Combination AMA1 Blood Stage Malaria Vaccine in Malian Children

Apical Membrane Antigen-1 (AMA1) is one of the leading blood stage malaria vaccine candidates. AMA1-C1/Alhydrogel consists of an equal mixture of recombinant AMA1 from FVO and 3D7 clones of P. falciparum, adsorbed onto Alhydrogel. A Phase 1 study in semi-immune adults in Mali showed that the vaccine was safe and immunogenic, with higher antibody responses in those who received the 80 microg dose. The aim of this study was to assess the safety and immunogenicity of this vaccine in young children in a malaria endemic area.This was a Phase 1 dose escalating study in 36 healthy children aged 2-3 years started in March 2006 in Donéguébougou, Mali. Eighteen children in the first cohort were randomized 2 ratio 1 to receive either 20 microg AMA1-C1/Alhydrogel or Haemophilus influenzae type b Hiberix vaccine. Two weeks later 18 children in the second cohort were randomized 2 ratio 1 to receive either 80 microg AMA1-C1/Alhydrogel or Haemophilus influenzae type b Hiberix vaccine. Vaccinations were administered on Days 0 and 28 and participants were examined on Days 1, 2, 3, 7, and 14 after vaccination and then about every two months. Results to Day 154 are reported in this manuscript.Of 36 volunteers enrolled, 33 received both vaccinations. There were 9 adverse events related to the vaccination in subjects who received AMA1-C1 vaccine and 7 in those who received Hiberix. All were mild to moderate. No vaccine-related serious or grade 3 adverse events were observed. There was no increase in adverse events with increasing dose of vaccine or number of immunizations. In subjects who received the test vaccine, antibodies to AMA1 increased on Day 14 and peaked at Day 42, with changes from baseline significantly different from subjects who received control vaccine.AMA-C1 vaccine is well tolerated and immunogenic in children in this endemic area although the antibody response was short lived.Clinicaltrials.gov NCT00341250

Bio-inspired CO₂ conversion by iron sulfide catalysts under sustainable conditions

The mineral greigite presents similar surface structures to the active sites found in many modern-day enzymes. We show that particles of greigite can reduce CO2 under ambient conditions into chemicals such as methanol, formic, acetic and pyruvic acid. Our results also lend support to the Origin of Life theory on alkaline hydrothermal vents

NQO1-Dependent Redox Cycling of Idebenone: Effects on Cellular Redox Potential and Energy Levels

Short-chain quinones are described as potent antioxidants and in the case of idebenone have already been under clinical investigation for the treatment of neuromuscular disorders. Due to their analogy to coenzyme Q10 (CoQ10), a long-chain quinone, they are widely regarded as a substitute for CoQ10. However, apart from their antioxidant function, this provides no clear rationale for their use in disorders with normal CoQ10 levels. Using recombinant NAD(P)H:quinone oxidoreductase (NQO) enzymes, we observed that contrary to CoQ10 short-chain quinones such as idebenone are good substrates for both NQO1 and NQO2. Furthermore, the reduction of short-chain quinones by NQOs enabled an antimycin A-sensitive transfer of electrons from cytosolic NAD(P)H to the mitochondrial respiratory chain in both human hepatoma cells (HepG2) and freshly isolated mouse hepatocytes. Consistent with the substrate selectivity of NQOs, both idebenone and CoQ1, but not CoQ10, partially restored cellular ATP levels under conditions of impaired complex I function. The observed cytosolic-mitochondrial shuttling of idebenone and CoQ1 was also associated with reduced lactate production by cybrid cells from mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) patients. Thus, the observed activities separate the effectiveness of short-chain quinones from the related long-chain CoQ10 and provide the rationale for the use of short-chain quinones such as idebenone for the treatment of mitochondrial disorders

IgG antibody responses to Plasmodium falciparum merozoite antigens in Kenyan children have a short half-life

BACKGROUND: Data suggest that antibody responses to malaria parasites merozoite antigens are generally short-lived and this has implications for serological studies and malaria vaccine designs. However, precise data on the kinetics of these responses is lacking. METHODS: IgG1 and IgG3 responses to five recombinant Plasmodium falciparum merozoite antigens (MSP-119, MSP-2 type A and B, AMA-1 ectodomain and EBA-175 region II) among Kenyan children were monitored using ELISA for 12 weeks after an acute episode of malaria and their half-lives estimated using an exponential decay model. RESULTS: The responses peaked mainly at week 1 and then decayed rapidly to very low levels within 6 weeks. Estimation of the half-lives of 40 IgG1 responses yielded a mean half-life of 9.8 days (95% CI: 7.6-12.0) while for 16 IgG3 responses it was 6.1 days (95% CI: 3.7-8.4), periods that are shorter than those normally described for the catabolic half-life of these antibody subclasses. CONCLUSION: This study indicates antibodies against merozoite antigens have very short half-lives and this has to be taken into account when designing serological studies and vaccines based on the antigens

Metagenomic Comparison of Two Thiomicrospira Lineages Inhabiting Contrasting Deep-Sea Hydrothermal Environments

Background: The most widespread bacteria in oxic zones of carbonate chimneys at the serpentinite-hosted Lost City hydrothermal field, Mid-Atlantic Ridge, belong to the Thiomicrospira group of sulfur-oxidizing chemolithoautotrophs. It is unclear why Thiomicrospira-like organisms thrive in these chimneys considering that Lost City hydrothermal fluids are notably lacking in hydrogen sulfide and carbon dioxide. Methodology/Principal Findings: Here we describe metagenomic sequences obtained from a Lost City carbonate chimney that are highly similar to the genome of Thiomicrospira crunogena XCL-2, an isolate from a basalt-hosted hydrothermal vent in the Pacific Ocean. Even though T. crunogena and Lost City Thiomicrospira inhabit different types of hydrothermal systems in different oceans, their genomic contents are highly similar. For example, sequences encoding the sulfur oxidation and carbon fixation pathways (including a carbon concentration mechanism) of T. crunogena are also present in the Lost City metagenome. Comparative genomic analyses also revealed substantial genomic changes that must have occurred since the divergence of the two lineages, including large genomic rearrangements, gene fusion events, a prophage insertion, and transposase activity. Conclusions/Significance: Our results show significant genomic similarity between Thiomicrospira organisms inhabiting different kinds of hydrothermal systems in different oceans, suggesting that these organisms are widespread and highl