Flower color-flower scent associations in polymorphic Hesperis matronalis (Brassicaceae)

Floral scent emission rate and composition of purple and white flower color morphs of Hesperis matronalis (Brassicaceae) were determined for two populations and, for each, at two times of day using dynamic headspace collection and GC-MS. The floral volatile compounds identified for this species fell into two main categories, terpenoids and aromatics. Principal component analysis of 30 compounds demonstrated that both color morphs emitted more scent at dusk than at dawn. Color morphs varied in chemical composition of scent, but this differed between populations. The white morphs exhibited significant differences between populations, while the purple morphs did not. In the white morphs, one population contains color-scent associations that match expectations from classical pollination syndrome theory, where the flowers have aromatic scents, which are expected to maximize night-flying moth pollinator attraction; in the second population, white morphs were strongly associated with terpenoid compounds. The potential impact that pollinators, conserved biosynthetic pathways, and the genetics of small colonizing populations may have in determining population-specific associations between floral color and floral scent are discussed.     

Vitamin D? Supplementation in Batswana Children and Adults with HIV: A Pilot Double Blind Randomized Controlled Trial

ObjectivesSince vitamin D insufficiency is common worldwide in people with HIV, we explored safety and efficacy of high dose cholecalciferol (D₃) in Botswana, and evaluated potential modifiers of serum 25 hydroxy vitamin D change (Δ25D).DesignProspective randomized double-blind 12-week pilot trial of subjects ages 5.0–50.9 years.MethodsSixty subjects randomized within five age groups to either 4000 or 7000IU per day of D₃ and evaluated for vitamin D, parathyroid hormone, HIV, safety and growth status. Efficacy was defined as serum 25 hydroxy vitamin D (25D) ≥32ng/mL, and safety as no simultaneous elevation of serum calcium and 25D. Also assessed were HIV plasma viral RNA viral load (VL), CD4%, anti-retroviral therapy (ART) regime, and height-adjusted (HAZ), weight-adjusted (WAZ) and Body Mass Index (BMIZ) Z scores.ResultsSubjects were 50% male, age (mean±SD) 19.5±11.8 years, CD4% 31.8±10.4, with baseline VL log₁₀ range of <1.4 to 3.8 and VL detectable (>1.4) in 22%. From baseline to 12 weeks, 25D increased from 36±9ng/ml to 56±18ng/ml (p<0.0001) and 68% and 90% had 25D ≥32ng/ml, respectively (p = 0.02). Δ25D was similar by dose. No subjects had simultaneously increased serum calcium and 25D. WAZ and BMIZ improved by 12 weeks (p<0.04). HAZ and CD4% increased and VL decreased in the 7000IU/d group (p<0.04). Younger (5–13y) and older (30–50y) subjects had greater Δ25D than those 14–29y (26±17 and 28±12 vs. 11±11ng/ml, respectively, p≤0.001). Δ25D was higher with efavirenz or nevirapine compared to protease inhibitor based treatment (22±12, 27±17, vs. 13±10, respectively, p≤0.03).ConclusionsIn a pilot study in Botswana, 12-week high dose D₃ supplementation was safe and improved vitamin D, growth and HIV status; age and ART regimen were significant effect modifiers.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02189902","term_id":"NCT02189902"}}NCT02189902     

Association of SNPs in EGR3 and ARC with Schizophrenia Supports a Biological Pathway for Schizophrenia Risk

We have previously hypothesized a biological pathway of activity-dependent synaptic plasticity proteins that addresses the dual genetic and environmental contributions to schizophrenia. Accordingly, variations in the immediate early gene EGR3, and its target ARC, should influence schizophrenia susceptibility. We used a pooled Next-Generation Sequencing approach to identify variants across these genes in U.S. populations of European (EU) and African (AA) descent. Three EGR3 and one ARC SNP were selected and genotyped for validation, and three SNPs were tested for association in a replication cohort. In the EU group of 386 schizophrenia cases and 150 controls EGR3 SNP rs1877670 and ARC SNP rs35900184 showed significant associations (p = 0.0078 and p = 0.0275, respectively). In the AA group of 185 cases and 50 controls, only the ARC SNP revealed significant association (p = 0.0448). The ARC SNP did not show association in the Han Chinese (CH) population. However, combining the EU, AA, and CH groups revealed a highly significant association of ARC SNP rs35900184 (p = 2.353 x 10⁻⁷; OR [95% CI] = 1.54 [1.310–1.820]). These findings support previously reported associations between EGR3 and schizophrenia. Moreover, this is the first report associating an ARC SNP with schizophrenia and supports recent large-scale GWAS findings implicating the ARC complex in schizophrenia risk. These results support the need for further investigation of the proposed pathway of environmentally responsive, synaptic plasticity-related, schizophrenia genes.     

A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo

The CD4 binding site (CD4bs) on the envelope glycoprotein is a major site of vulnerability that is conserved among different HIV-1 isolates. Many broadly neutralizing antibodies (bNAbs) to the CD4bs belong to the VRC01 class, sharing highly restricted origins, recognition mechanisms and viral escape pathways. We sought to isolate new anti-CD4bs bNAbs with different origins and mechanisms of action. Using a gp120 2CC core as bait, we isolated antibodies encoded by IGVH3-21 and IGVL3-1 genes with long CDRH3s that depend on the presence of the N-linked glycan at position-276 for activity. This binding mode is similar to the previously identified antibody HJ16, however the new antibodies identified herein are more potent and broad. The most potent variant, 179NC75, had a geometric mean IC₈₀ value of 0.42 μg/ml against 120 Tier-2 HIV-1 pseudoviruses in the TZM.bl assay. Although this group of CD4bs glycan-dependent antibodies can be broadly and potently neutralizing in vitro, their in vivo activity has not been tested to date. Here, we report that 179NC75 is highly active when administered to HIV-1-infected humanized mice, where it selects for escape variants that lack a glycan site at position-276. The same glycan was absent from the virus isolated from the 179NC75 donor, implying that the antibody also exerts selection pressure in humans.     

Origin and functional significance of large-scale chromosomal imbalances in neuroblastoma

Neuroblastoma is characterized by numerous recurrent large-scale chromosomal imbalances and gene amplifications which are associated with poor clinical outcome. The most common include MYCN amplification, loss of 1p, 3p and 11q, and gain of 17q genomic regions. Two of these abnormalities, MYCN amplification and loss of 11q, define different genetic subtypes of the disease with vastly different global gene expression profiles. The progress towards the identification of the genes and genetic pathways that have been affected by these abnormalities is reviewed and high resolution mapping of the chromosomal breakpoint regions using oligonucleotide array CGH (oaCGH) is discussed. oaCGH analysis is proving useful for both defining minimal regions of overlap of imbalances, as well as providing information on the molecular mechanisms that generate the chromosomal imbalances. These high resolution analyses have also permitted the detection of micro-deletions in the tumors that further assist in identifying genes important for neuroblastoma pathogenesis.     

Intercalation Model for DNA-Cross Linking in a 1-Nitro-9-aminoacridine Derivative,an Analog of the Antitumor Agent “Ledakrin” (Nitracrine)

Abstract

Ledakrin (nitracrine), C-283, is a 1-nitro-9-aminoacridine derivative that is used in Poland as an antitumor agent. In order to investigate the basis of the activity of this compound the structure of another analog, [9-(3-dimethyl-l-methylpropylimino)-l-nitro-9, 10-dihydroacridine], C-829, that has similar activity, was determined by X-ray crystallographic techniques and was compared with that of ledakrin, already reported in the literature. In both molecules the proximity of the 1-nitro to the substituted 9-aminoacridine group causes extensive distortions. These compounds are believed to act, after metabolic “activation”, by cross-linking DNA. Such cross-linking does not occur in the absence of the 1-nitro group or if the nitro group is moved to the 2-, 3- or 4-position. Computer-assisted model-building has been used to test possible intercalative models. It has shown that functional groups on C-829 or C-283 are, when the acridine portion of the molecule is intercalated as in a proflavine dinucleoside phosphate complex, in positions suitable for DNA cross-linking by activated 1-nitro- 9-aminoacridine derivatives.     

Energy allocation in juveniles of a warm-temperate reef fish

During the first year of life, organisms are faced with competing demands for energy between growth and storage. Most research on energy allocation in young fishes has focused on cold-temperate species which are subjected to strong seasonal fluctuations in productivity, while few studies have considered those at lower latitudes where seasonality is less pronounced. Gag (Mycteroperca microlepis) of the northeastern Gulf of Mexico settle in coastal seagrass beds in the spring as juveniles and emigrate to offshore reefs in the fall. Upon settlement, these young fish grow at remarkably fast rates, but their growth slows considerably before emigration. Slowed growth can be explained by one of three hypotheses: (1) size-specific emigration times; (2) reduced feeding efficiency associated with declines in primary and secondary productivity; or (3) energetic shifts in allocation from growth to storage. Gag emigrate essentially as a cohort, so slowed growth does not result from differential emigration patterns based on fish size. They also emigrate before seasonal declines in primary and secondary productivity; thus, food remains abundant and feeding efficiency constant. The more plausible hypothesis is that there is an energetic shift from growth to storage. The liver serves as the primary site of lipid storage and the hepatosomatic index of juvenile gag increases coincident with reduced growth. The overall effect of increased energy stores is presumably for use during offshore migration and/or for overwinter survival.     

Incidence of HIV-1 infection in a rural region of Uganda.

OBJECTIVE--To determine the incidence of infection with HIV-1 and the risk factors associated with seroconversion in three geographical strata of a rural Ugandan district. DESIGN--Serological, sociodemographic, and behavioural surveys of everyone aged 13 or more in 21 randomly selected communities at baseline and one year later. SETTING--Rural population of Rakai district, southwestern Uganda, residing in main road trading centres, secondary trading villages, and agricultural villages. SUBJECTS--In 1989, 1292 adults provided a blood sample and interview data; one year later, 778 survivors (77%) who had been seronegative at baseline provided follow up data. MAIN OUTCOME MEASURES--Incidence of HIV infection in relation to individual characteristics and risk factors, including place of residence. RESULTS--Incidence of HIV infection in all adults was 2.1/100 person years of observation (SE 0.5 (95% confidence interval 1.1 to 3.1)); in people aged 15-39 the incidence was 3.2/100 person years. Incidence was highest in men and women aged 20-24 (9.2/100 person years (3.9) and 6.8/100 person years (2.9) respectively). Risk factors significantly associated with seroconversion were age 24 and under and two or more sexual partners. Between the surveys the proportion of all respondents reporting high risk behaviour (two or more partners) significantly increased from 8.9% to 12.3%. CONCLUSIONS--Despite preventive programmes and substantial knowledge about AIDS the incidence of HIV infection remains high in this rural population. Prevention aimed at vulnerable rural communities is urgently needed to contain the HIV epidemic.