Clear and independent associations of several HLA-DRB1 alleles with differential antibody responses to hepatitis B vaccination in youth

To confirm and refine associations of human leukocyte antigen (HLA) genotypes with variable antibody (Ab) responses to hepatitis B vaccination, we have analyzed 255 HIV-1 seropositive (HIV+) youth and 80 HIV-1 seronegatives (HIV−) enrolled into prospective studies. In univariate analyses that focused on HLA-DRB1, -DQA1, and -DQB1 alleles and haplotypes, the DRB1*03 allele group and DRB1*0701 were negatively associated with the responder phenotype (serum Ab concentration ≥ 10 mIU/mL) (P = 0.026 and 0.043, respectively). Collectively, DRB1*03 and DRB1*0701 were found in 42 (53.8%) out of 78 non-responders (serum Ab <10 mIU/mL), 65 (40.6%) out of 160 medium responders (serum Ab 10–1,000 mIU/mL), and 27 (27.8%) out of 97 high responders (serum Ab >1,000 mIU/mL) (P < 0.001 for trend). Meanwhile, DRB1*08 was positively associated with the responder phenotype (P = 0.010), mostly due to DRB1*0804 (P = 0.008). These immunogenetic relationships were all independent of non-genetic factors, including HIV-1 infection status and immunodeficiency. Alternative analyses confined to HIV+ youth or Hispanic youth led to similar findings. In contrast, analyses of more than 80 non-coding, single nucleotide polymorphisms within and beyond the three HLA class II genes revealed no clear associations. Overall, several HLA-DRB1 alleles were major predictors of differential Ab responses to hepatitis B vaccination in youth, suggesting that T-helper cell-dependent pathways mediated through HLA class II antigen presentation are critical to effective immune response to recombinant vaccines

Towards disappearing user interfaces for ubiquitous computing: human enhancement from sixth sense to super senses

The enhancement of human senses electronically is possible when pervasive computers interact unnoticeably with humans in Ubiquitous Computing. The design of computer user interfaces towards “disappearing” forces the interaction with humans using a content rather than a menu driven approach, thus the emerging requirement for huge number of non-technical users interfacing intuitively with billions of computers in the Internet of Things is met. Learning to use particular applications in Ubiquitous Computing is either too slow or sometimes impossible so the design of user interfaces must be naturally enough to facilitate intuitive human behaviours. Although humans from different racial, cultural and ethnic backgrounds own the same physiological sensory system, the perception to the same stimuli outside the human bodies can be different. A novel taxonomy for Disappearing User Interfaces (DUIs) to stimulate human senses and to capture human responses is proposed. Furthermore, applications of DUIs are reviewed. DUIs with sensor and data fusion to simulate the Sixth Sense is explored. Enhancement of human senses through DUIs and Context Awareness is discussed as the groundwork enabling smarter wearable devices for interfacing with human emotional memories

Clues to Neuro-Degeneration in Niemann-Pick Type C Disease from Global Gene Expression Profiling

BACKGROUND: Niemann-Pick Type C (NPC) disease is a neurodegenerative disease that is characterized by the accumulation of cholesterol and glycosphingolipids in the late endocytic pathway. The majority of NPC cases are due to mutations in the NPC1 gene. The precise function of this gene is not yet known. METHODOLOGY/PRINCIPAL FINDINGS: Using cDNA microarrays, we analyzed the genome-wide expression patterns of human fibroblasts homozygous for the I1061T NPC1 mutation that is characterized by a severe defect in the intracellular processing of low density lipoprotein-derived cholesterol. A distinct gene expression profile was identified in NPC fibroblasts from different individuals when compared with fibroblasts isolated from normal subjects. As expected, NPC1 mutant cells displayed an inappropriate homeostatic response to accumulated intracellular cholesterol. In addition, a number of striking parallels were observed between NPC disease and Alzheimer's disease. CONCLUSIONS/SIGNIFICANCE: Many genes involved in the trafficking and processing of amyloid precursor protein and the microtubule binding protein, tau, were more highly expressed. Numerous genes important for membrane traffic and the cellular regulation of calcium, metals and other ions were upregulated. Finally, NPC fibroblasts exhibited a gene expression profile indicative of oxidative stress. These changes are likely contributors to the pathophysiology of Niemann-Pick Type C disease

Quantitative and Qualitative Stem Rust Resistance Factors in Barley Are Associated with Transcriptional Suppression of Defense Regulons

Stem rust (Puccinia graminis f. sp. tritici; Pgt) is a devastating fungal disease of wheat and barley. Pgt race TTKSK (isolate Ug99) is a serious threat to these Triticeae grain crops because resistance is rare. In barley, the complex Rpg-TTKSK locus on chromosome 5H is presently the only known source of qualitative resistance to this aggressive Pgt race. Segregation for resistance observed on seedlings of the Q21861 × SM89010 (QSM) doubled-haploid (DH) population was found to be predominantly qualitative, with little of the remaining variance explained by loci other than Rpg-TTKSK. In contrast, analysis of adult QSM DH plants infected by field inoculum of Pgt race TTKSK in Njoro, Kenya, revealed several additional quantitative trait loci that contribute to resistance. To molecularly characterize these loci, Barley1 GeneChips were used to measure the expression of 22,792 genes in the QSM population after inoculation with Pgt race TTKSK or mock-inoculation. Comparison of expression Quantitative Trait Loci (eQTL) between treatments revealed an inoculation-dependent expression polymorphism implicating Actin depolymerizing factor3 (within the Rpg-TTKSK locus) as a candidate susceptibility gene. In parallel, we identified a chromosome 2H trans-eQTL hotspot that co-segregates with an enhancer of Rpg-TTKSK-mediated, adult plant resistance discovered through the Njoro field trials. Our genome-wide eQTL studies demonstrate that transcript accumulation of 25% of barley genes is altered following challenge by Pgt race TTKSK, but that few of these genes are regulated by the qualitative Rpg-TTKSK on chromosome 5H. It is instead the chromosome 2H trans-eQTL hotspot that orchestrates the largest inoculation-specific responses, where enhanced resistance is associated with transcriptional suppression of hundreds of genes scattered throughout the genome. Hence, the present study associates the early suppression of genes expressed in this host–pathogen interaction with enhancement of R-gene mediated resistance

Changes in the geographical distribution of plant species and climatic variables on the West Cornwall peninsula (South West UK)

Recent climate change has had a major impact on biodiversity and has altered the geographical distribution of vascular plant species. This trend is visible globally; however, more local and regional scale research is needed to improve understanding of the patterns of change and to develop appropriate conservation strategies that can minimise cultural, health, and economic losses at finer scales. Here we describe a method to manually geo-reference botanical records from a historical herbarium to track changes in the geographical distributions of plant species in West Cornwall (South West England) using both historical (pre-1900) and contemporary (post-1900) distribution records. We also assess the use of Ellenberg and climate indicator values as markers of responses to climate and environmental change. Using these techniques we detect a loss in 19 plant species, with 6 species losing more than 50% of their previous range. Statistical analysis showed that Ellenberg (light, moisture, nitrogen) and climate indicator values (mean January temperature, mean July temperature and mean precipitation) could be used as environmental change indicators. Significantly higher percentages of area lost were detected in species with lower January temperatures, July temperatures, light, and nitrogen values, as well as higher annual precipitation and moisture values. This study highlights the importance of historical records in examining the changes in plant species’ geographical distributions. We present a method for manual geo-referencing of such records, and demonstrate how using Ellenberg and climate indicator values as environmental and climate change indicators can contribute towards directing appropriate conservation strategies

Quantum Rings in Electromagnetic Fields

This is the author accepted manuscript. The final version is available from Springer via the DOI in this recordThis chapter is devoted to optical properties of so-called Aharonov-Bohm quantum rings (quantum rings pierced by a magnetic flux resulting in AharonovBohm oscillations of their electronic spectra) in external electromagnetic fields. It studies two problems. The first problem deals with a single-electron AharonovBohm quantum ring pierced by a magnetic flux and subjected to an in-plane (lateral) electric field. We predict magneto-oscillations of the ring electric dipole moment. These oscillations are accompanied by periodic changes in the selection rules for inter-level optical transitions in the ring allowing control of polarization properties of the associated terahertz radiation. The second problem treats a single-mode microcavity with an embedded Aharonov-Bohm quantum ring which is pierced by a magnetic flux and subjected to a lateral electric field. We show that external electric and magnetic fields provide additional means of control of the emission spectrum of the system. In particular, when the magnetic flux through the quantum ring is equal to a half-integer number of the magnetic flux quanta, a small change in the lateral electric field allows for tuning of the energy levels of the quantum ring into resonance with the microcavity mode, thus providing an efficient way to control the quantum ring-microcavity coupling strength. Emission spectra of the system are discussed for several combinations of the applied magnetic and electric fields

Clusters of Basic Amino Acids Contribute to RNA Binding and Nucleolar Localization of Ribosomal Protein L22

The ribosomal protein L22 is a component of the 60S eukaryotic ribosomal subunit. As an RNA-binding protein, it has been shown to interact with both cellular and viral RNAs including 28S rRNA and the Epstein-Barr virus encoded RNA, EBER-1. L22 is localized to the cell nucleus where it accumulates in nucleoli. Although previous studies demonstrated that a specific amino acid sequence is required for nucleolar localization, the RNA-binding domain has not been identified. Here, we investigated the hypothesis that the nucleolar accumulation of L22 is linked to its ability to bind RNA. To address this hypothesis, mutated L22 proteins were generated to assess the contribution of specific amino acids to RNA binding and protein localization. Using RNA-protein binding assays, we demonstrate that basic amino acids 80–93 are required for high affinity binding of 28S rRNA and EBER-1 by L22. Fluorescence localization studies using GFP-tagged mutated L22 proteins further reveal that basic amino acids 80–93 are critical for nucleolar accumulation and for incorporation into ribosomes. Our data support the growing consensus that the nucleolar accumulation of ribosomal proteins may not be mediated by a defined localization signal, but rather by specific interaction with established nucleolar components such as rRNA

Frequent and Recent Human Acquisition of Simian Foamy Viruses Through Apes' Bites in Central Africa

Human infection by simian foamy viruses (SFV) can be acquired by persons occupationally exposed to non-human primates (NHP) or in natural settings. This study aimed at getting better knowledge on SFV transmission dynamics, risk factors for such a zoonotic infection and, searching for intra-familial dissemination and the level of peripheral blood (pro)viral loads in infected individuals. We studied 1,321 people from the general adult population (mean age 49 yrs, 640 women and 681 men) and 198 individuals, mostly men, all of whom had encountered a NHP with a resulting bite or scratch. All of these, either Pygmies (436) or Bantus (1085) live in villages in South Cameroon. A specific SFV Western blot was used and two nested PCRs (polymerase, and LTR) were done on all the positive/borderline samples by serology. In the general population, 2/1,321 (0.2%) persons were found to be infected. In the second group, 37/198 (18.6%) persons were SFV positive. They were mostly infected by apes (37/39) FV (mainly gorilla). Infection by monkey FV was less frequent (2/39). The viral origin of the amplified sequences matched with the history reported by the hunters, most of which (83%) are aged 20 to 40 years and acquired the infection during the last twenty years. The (pro)viral load in 33 individuals infected by a gorilla FV was quite low (<1 to 145 copies per 105 cells) in the peripheral blood leucocytes. Of the 30 wives and 12 children from families of FV infected persons, only one woman was seropositive in WB without subsequent viral DNA amplification. We demonstrate a high level of recent transmission of SFVs to humans in natural settings specifically following severe gorilla bites during hunting activities. The virus was found to persist over several years, with low SFV loads in infected persons. Secondary transmission remains an open question