The Robustness of Recombination Frequency Estimates in Intercrosses with Dominant Markers

The robustness of the maximum likelihood estimates of recombination frequencies has been investigated in double intercrosses with complete dominance at both loci. The robustness was investigated with respect to bias in the recombination frequency estimates due to: (1) limited sample sizes, (2) heterogeneity in recombination frequencies between sexes or among meioses and (3) factors that distort the segregation-misclassification or differential viability. In the coupling phase, the recombination frequency estimates are quite robust with respect to most of the investigated factors. Potentially, the most serious cause of a bias is misclassifications, which tend to increase the recombination frequency estimates. In the repulsion phase, misclassifications are particularly serious, leading to extreme discrepancies between true and observed values. In addition, limited sample size and sex differences in recombination can also bias recombination frequency estimates in repulsion. These effects may pose serious problem in genetic mapping with random amplified polymorphic DNA (RAPD) markers.     

A novel fluorescent sensor based on electrosynthesized benzene sulfonic acid‐doped polypyrrole for determination of Pb(II) and Cu(II)

To develop conducting organic polymers (COPs) as luminescent sensors for determination of toxic heavy metals, a new benzene sulfonic acid‐doped polypyrrole (PPy‐BSA) thin film was electrochemically prepared by cyclic voltammetry (CV) on flexible indium tin oxide (ITO) electrode in aqueous solution. PPy‐BSA film was characterized by FTIR spectrometry, X‐ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The optical properties of PPy‐BSA were investigated by ultraviolet (UV)‐visible absorption and fluorescence spectrometry in dimethylsulfoxide (DMSO) diluted solutions. PPy‐BSA fluorescence spectra were strongly quenched upon increasing copper(II) ion (Cu²⁺) and lead(II) ion (Pb²⁺) concentrations in aqueous medium, and linear Stern–Volmer relationships were obtained, which indicated the existence of a main dynamic fluorescence quenching mechanism. BSA‐PPy sensor showed a high sensitivity for detection of both metallic ions, Cu²⁺ and Pb²⁺, with very low limit of detection values of 3.1 and 18.0 nM, respectively. The proposed quenching‐fluorimetric sensor might be applied to the determination of traces of toxic heavy metallic ions in water samples.     

Diamino benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors: 3. Enhancing activity by imposing conformational restriction in the C-4" side chain

The preparation and biological evaluation of a series of benzo[b]thiophene diamine thrombin inhibitors possessing conformationally restricted C-4" linkers are reported. Compared to the parent compounds 1a/b, the unsaturated derivatives 3a/b exhibited a modest twofold increase in thrombin inhibitory activity, while the more lipophilic carbocyclic ring containing analogs 4a/b affected an eightfold enhancement in potency.     

Biochemical aspects of flight and flightlessness in Gryllus: flight fuels,enzyme activities and electrophoretic profiles of flight muscles from flight-capable and flightless morphs

Female Gryllus assimilis subjected to 4.5-7.7h continuous tethered flight had significantly lower amounts of total lipid, triglyceride and total soluble carbohydrate compared with unflown controls. A much greater amount of total lipid (6.3mg) was used during flight compared with carbohydrate (0.14mg). Flown individuals also had substantially reduced amounts of injected, radiolabeled [(14)C]-oleic acid. Activities of lipid, carbohydrate and amino acid catabolizing enzymes in flight muscles of G. assimilis and its wing-polymorphic congener, G. firmus, were very similar to activities in insects which primarily utilize lipid to power flight. By contrast, enzyme activities were very different from those in insects which primarily or exclusively use carbohydrate or proline as a flight fuel. These results strongly implicate lipid as the major flight fuel in Gryllus. Previous studies have shown that lipid levels are higher in flight-capable (long-winged) G. firmus that have small ovaries compared with flightless (short-winged) females that have large ovaries. Results of the present and previous studies collectively indicate that elevated lipid in long-winged G. firmus represents an energetic cost of flight capability which reduces (trade-offs with) reproduction in Gryllus. In G. firmus, mass-specific activities of nearly all enzymes were considerably reduced in underdeveloped, and to a lesser degree in histolyzed muscle, compared with fully-developed flight muscle. An important exception was alanine aminotransferase, whose activity was the highest in histolyzed muscle, and which may be involved in the catabolism of amino acids derived from muscle degradation. Despite the dramatic differences in enzyme activity, electrophoretic profiles of soluble flight-muscle proteins differed only subtly between fully-developed and underdeveloped or histolyzed flight muscles.     

Expression of SR-BI receptor and StAR protein in rat ocular tissues

The class-B type-I scavenger receptor (SR-BI) plays a key role in cholesterol homeostasis; it mediates the selective uptake of lipoprotein cholesterol to steroidogenic tissues. We show by RT-PCR, western blot, in situ hybridization and immunohistochemistry analysis that SR-BI is highly expressed in different neuro-retinal and non-neuronal cells types on rat eye. Immunohistochemistry of the steroidogenic acute regulatory protein (StAR) involved in neurosteroid production showed the same expression pattern than SR-BI in rat eye. Our results may suggest a key role of these genes in the ocular cholesterol metabolism for membranes biosynthesis and neurosteroidogenesis.     

High Prevalence of Severe Food Insecurity and Malnutrition among HIV-Infected Adults in Senegal,West Africa

Background

Malnutrition and food insecurity are associated with increased mortality and poor clinical outcomes among people living with HIV/AIDS; however, the prevalence of malnutrition and food insecurity among people living with HIV/AIDS in Senegal, West Africa is unknown. The objective of this study was to determine the prevalence and severity of food insecurity and malnutrition among HIV-infected adults in Senegal, and to identify associations between food insecurity, malnutrition, and HIV outcomes.

Methods

We conducted a cross-sectional study at outpatient clinics in Dakar and Ziguinchor, Senegal. Data were collected using participant interviews, anthropometry, the Household Food Insecurity Access Scale, the Individual Dietary Diversity Scale, and chart review.

Results

One hundred and nine HIV-1 and/or HIV-2 participants were enrolled. The prevalence of food insecurity was 84.6% in Dakar and 89.5% in Ziguinchor. The prevalence of severe food insecurity was 59.6% in Dakar and 75.4% in Ziguinchor. The prevalence of malnutrition (BMI <18.5) was 19.2% in Dakar and 26.3% in Ziguinchor. Severe food insecurity was associated with missing clinic appointments (p = 0.01) and not taking antiretroviral therapy due to hunger (p = 0.02). Malnutrition was associated with lower CD4 cell counts (p = 0.01).

Conclusions

Severe food insecurity and malnutrition are highly prevalent among HIV-infected adults in both Dakar and Ziguinchor, and are associated with poor HIV outcomes. Our findings warrant further studies to determine the root causes of malnutrition and food insecurity in Senegal, and the short- and long-term impacts of malnutrition and food insecurity on HIV care. Urgent interventions are needed to address the unacceptably high rates of malnutrition and food insecurity in this population.     

HIV-2 Integrase Variation in Integrase Inhibitor-Na?ve Adults in Senegal,West Africa

Background

Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.

Methods

We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2–infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1.

Results

No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein.

Conclusion

Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at “secondary” HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2–infected patients.     

Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection

The biological role of the protein encoded by the alternative open reading frame (core+1/ARF) of the Hepatitis C virus (HCV) genome remains elusive, as does the significance of the production of corresponding antibodies in HCV infection. We investigated the prevalence of anti-core and anti-core+1/ARFP antibodies in HCV-positive blood donors from Cambodia, using peptide and recombinant protein-based ELISAs. We detected unusual serological profiles in 3 out of 58 HCV positive plasma of genotype 1a. These patients were negative for anti-core antibodies by commercial and peptide-based assays using C-terminal fragments of core but reacted by Western Blot with full-length core protein. All three patients had high levels of anti-core+1/ARFP antibodies. Cloning of the cDNA that corresponds to the core-coding region from these sera resulted in the expression of both core and core+1/ARFP in mammalian cells. The core protein exhibited high amino-acid homology with a consensus HCV1a sequence. However, 10 identical synonymous mutations were found, and 7 were located in the aa(99-124) region of core. All mutations concerned the third base of a codon, and 5/10 represented a T>C mutation. Prediction analyses of the RNA secondary structure revealed conformational changes within the stem-loop region that contains the core+1/ARFP internal AUG initiator at position 85/87. Using the luciferase tagging approach, we showed that core+1/ARFP expression is more efficient from such a sequence than from the prototype HCV1a RNA. We provide additional evidence of the existence of core+1/ARFP in vivo and new data concerning expression of HCV core protein. We show that HCV patients who do not produce normal anti-core antibodies have unusually high levels of anti-core+1/ARFP and harbour several identical synonymous mutations in the core and core+1/ARFP coding region that result in major changes in predicted RNA structure. Such HCV variants may favour core+1/ARFP production during HCV infection.     

The evolution of the multicoloured face of mandrills: insights from the perceptual space of colour vision

Multicomponent signals consist of several traits that are perceived as a whole. Although many animals rely on multicomponent signals to communicate, the selective pressures shaping these signals are still poorly understood. Previous work has mainly investigated the evolution of multicomponent signals by studying each trait individually, which may not accurately reflect the selective pressures exerted by the holistic perception of signal receivers. Here, we study the design of the multicoloured face of an Old World primate, the mandrill (Mandrillus sphinx), in relation to two aspects of signalling that are expected to be selected by receivers: conspicuousness and information. Using reflectance data on the blue and red colours of the faces of 34 males and a new method of hue vectorisation in a perceptual space of colour vision, we show that the blue hue maximises contrasts to both the red hue and the foliage background colouration, thereby increasing the conspicuousness of the whole display. We further show that although blue saturation, red saturation and the contrast between blue and red colours are all correlated with dominance, dominance is most accurately indicated by the blue-red contrast. Taken together our results suggest that the evolution of blue and red facial colours in male mandrills are not independent and are likely driven by the holistic perception of conspecifics. In this view, we propose that the multicoloured face of mandrills acts as a multicomponent signal. Last, we show that information accuracy increases with the conspicuousness of the whole display, indicating that both aspects of signalling can evolve in concert.