Elucidating the role of hyperfine interactions on organic magnetoresistance using deuterated aluminium tris(8-hydroxyquinoline)

Measurements of the effect of a magnetic field on the light output and current through an organic light emitting diode made with deuterated aluminium tris(8-hydroxyquinoline) have shown that hyperfine coupling with protons is not the cause of the intrinsic organic magnetoresistance. We suggest that interactions with unpaired electrons in the device may be responsible.Comment: Submitte

Importance of Spin-Orbit Interaction for the Electron Spin Relaxation in Organic Semiconductors

Despite the great interest organic spintronics has recently attracted, there is only a partial understanding of the fundamental physics behind electron spin relaxation in organic semiconductors. Mechanisms based on hyperfine interaction have been demonstrated, but the role of the spin-orbit interaction remains elusive. Here, we report muon spin spectroscopy and time-resolved photoluminescence measurements on two series of molecular semiconductors in which the strength of the spin-orbit interaction has been systematically modified with a targeted chemical substitution of different atoms at a particular molecular site. We find that the spin-orbit interaction is a significant source of electron spin relaxation in these materials

Double ring-closing approach for the synthesis of 2,3,6,7-substituted anthracene derivatives.

A method for the synthesis of 2,3,6,7-substituted anthracene derivatives, one of the most challenging anthracene substitution patterns to obtain, is presented. The method is exemplified by the preparation of 2,3,6,7-anthracenetetracarbonitrile and employs a newly developed, stable, protected 1,2,4,5-benzenetetracarbaldehyde as the precursor. The precursor can be obtained in two scalable synthetic steps from 2,5-dibromoterephthalaldehyde and is converted into the anthracene derivative by a double intermolecular Wittig reaction under very mild conditions, followed by a deprotection and intramolecular double ring-closing condensation reaction

An Anti-HIV-1 V3 Loop Antibody Fully Protects Cross-Clade and Elicits T-Cell Immunity in Macaques Mucosally Challenged with an R5 Clade C SHIV

Neutralizing antibodies have been shown to protect macaques against SHIV challenge. However, genetically diverse HIV-1 clades have evolved, and a key question left unanswered is whether neutralizing antibodies can confer cross-clade protection in vivo. The novel human monoclonal antibody HGN194 was isolated from an individual infected with an HIV-1 clade AG recombinant circulating recombinant form (CRF). HGN194 targets an epitope in the third hypervariable loop (V3) of HIV-1 gp120 and neutralizes a range of relatively neutralization-sensitive and resistant viruses. We evaluated the potential of HGN194 to protect infant rhesus monkeys against a SHIV encoding a primary CCR5-tropic HIV-1 clade C envelope. After high-dose mucosal challenge, all untreated controls became highly viremic while all HGN194-treated animals (50 mg/kg) were completely protected. When HGN194 was given at 1 mg/kg, one out of two monkeys remained aviremic, whereas the other had delayed, lower peak viremia. Interestingly, all protected monkeys given high-dose HGN194 developed Gag-specific proliferative responses of both CD4+ and CD8+ T cells. To test whether generation of the latter involved cryptic infection, we ablated CD8+ cells after HGN194 clearance. No viremia was detected in any protected monkeys, thus ruling out virus reservoirs. Thus, induction of CD8 T-cell immunity may have resulted from transient “Hit and Run” infection or cross priming via Ag-Ab-mediated cross-presentation. Together, our data identified the HGN194 epitope as protective and provide proof-of-concept that this anti-V3 loop mAb can prevent infection with sterilizing immunity after challenge with virus of a different clade, implying that V3 is a potential vaccine target

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c

Inscribing a discipline: tensions in the field of bioinformatics

Bioinformatics, the application of computer science to biological problems, is a central feature of post-genomic science which grew rapidly during the 1990s and 2000s. Post-genomic science is often high-throughput, involving the mass production of inscriptions [Latour and Woolgar (1986), Laboratory Life: the Construction of Scientific Facts. Princeton, NJ: Princeton University Press]. In order to render these mass inscriptions comprehensible, bioinformatic techniques are employed, with bioinformaticians producing what we call secondary inscriptions. However, despite bioinformaticians being highly skilled and credentialed scientists, the field struggles to develop disciplinary coherence. This paper describes two tensions militating against disciplinary coherence. The first arises from the fact that bioinformaticians as producers of secondary inscriptions are often institutionally dependent, subordinate even, to biologists. With bioinformatics positioned as service, it cannot determine its own boundaries but has them imposed from the outside. The second tension is a result of the interdisciplinary origin of bioinformatics – computer science and biology are disciplines with very different cultures, values and products. The paper uses interview data from two different UK projects to describe and examine these tensions by commenting on Calvert's [(2010) “Systems Biology, Interdisciplinarity and Disciplinary Identity.” In Collaboration in the New Life Sciences, edited by J. N. Parker, N. Vermeulen and B. Penders, 201–219. Farnham: Ashgate] notion of individual and collaborative interdisciplinarity and McNally's [(2008) “Sociomics: CESAGen Multidisciplinary Workshop on the Transformation of Knowledge Production in the Biosciences, and its Consequences.” Proteomics 8: 222–224] distinction between “black box optimists” and “black box pessimists.

Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.This work was supported by the Biotechnology and Biological Sciences Research Council and by the Wellcome Trust.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100514

Ethical and legal implications of whole genome and whole exome sequencing in African populations

BACKGROUND: Rapid advances in high throughput genomic technologies and next generation sequencing are making medical genomic research more readily accessible and affordable, including the sequencing of patient and control whole genomes and exomes in order to elucidate genetic factors underlying disease. Over the next five years, the Human Heredity and Health in Africa (H3Africa) Initiative, funded by the Wellcome Trust (United Kingdom) and the National Institutes of Health (United States of America), will contribute greatly towards sequencing of numerous African samples for biomedical research. DISCUSSION: Funding agencies and journals often require submission of genomic data from research participants to databases that allow open or controlled data access for all investigators. Access to such genotype-phenotype and pedigree data, however, needs careful control in order to prevent identification of individuals or families. This is particularly the case in Africa, where many researchers and their patients are inexperienced in the ethical issues accompanying whole genome and exome research; and where an historical unidirectional flow of samples and data out of Africa has created a sense of exploitation and distrust. In the current study, we analysed the implications of the anticipated surge of next generation sequencing data in Africa and the subsequent data sharing concepts on the protection of privacy of research subjects. We performed a retrospective analysis of the informed consent process for the continent and the rest-of-the-world and examined relevant legislation, both current and proposed. We investigated the following issues: (i) informed consent, including guidelines for performing culturally-sensitive next generation sequencing research in Africa and availability of suitable informed consent documents; (ii) data security and subject privacy whilst practicing data sharing; (iii) conveying the implications of such concepts to research participants in resource limited settings. SUMMARY: We conclude that, in order to meet the unique requirements of performing next generation sequencing-related research in African populations, novel approaches to the informed consent process are required. This will help to avoid infringement of privacy of individual subjects as well as to ensure that informed consent adheres to acceptable data protection levels with regard to use and transfer of such information

Developmental constraint underlies the replicated evolution of grass awns

Replicated evolution, in which traits repeatedly evolve in distantly related species, can provide insights into the mechanisms underlying evolution and how structures are generated. One example of replicated evolution is the grass awn, an organ elaboration in inflorescences. We focus on lemma awns in the Pooideae, the largest grass subfamily with high variation in awn morphology. Using ancestral state estimations, we discovered that awns emerge about twice as often as they are lost in the Pooideae, and have been independently derived at least 25 times. Independent derivations share similarities in micromorphology and anatomy, but awn function is not conserved. Differences in partition development can explain diversity in morphology at maturity, despite a shared underlying pattern of development. In two species with independently derived awns and different awn morphology, we find a role for the YABBY-family transcription factor gene DROOPING LEAF in awn initiation. Together, these data support a role for developmental constraints in the replicated evolution of awns in the Pooideae