XLMR genes: update 2000

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B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Analysis of sexual phenotype and prezygotic fertility in natural populations of Fucus spiralis, F. vesiculosus (Fucaceae, Phaeophyceae) and their putative hybrids

In the genus Fucus, the character dioecy/hermaphroditism has undergone multiple state changes and hybridization is possible between taxa with contrasting mating systems, e.g. between the dioecious Fucus vesiculosus and the hermaphrodite F. spiralis. In the context of mating system evolution, we evaluated the potential consequences of hybridization by studying the variation in sexual phenotype and prezygotic fertility. Firstly, as a result of hybridization between the two sexual systems, gender variation may arise depending on the relative importance of genes with large versus small phenotypic effects. We thus qualitatively examined the extent of gender variation within and among individual hybrids in comparison with both parental species. Secondly, if hybridization breaks up co-adapted gene complexes, hybrid fertility may be reduced in comparison with both parental species. Therefore, we also quantified male and female prezygotic fertility in parental species and their hybrids in order to test for reduction in hybrid fitness. A total of 89 sexually mature individuals (20 F. spiralis, 40 F. vesiculosus, 10 hermaphrodite hybrids and 19 dioecious hybrids) were sampled in two geographically distant regions (France and Portugal) and six conceptacles per individual were observed. Within-individual variation was very restricted qualitatively – only one hybrid carried a conceptacle with a different sexual phenotype from the five others – as well as quantitatively. This suggests a simple genetic system for sex determination involving a few genes with major effects. In addition, analyses showed no significant decrease in hybrid fertility compared with parental species. Moreover, hybrids exhibited all sexual phenotypes, suggesting several generations of hybridization and backcrossing and, therefore, that hybrids are reproductively successful. Finally, the occurrence of sterile paraphyses in female and hermaphrodite individuals was interpreted as a relic of male function and suggests that, as in higher plants, evolution from hermaphroditism to dioecy may be the most parsimonious pathway

Causes and Correlates of Calf Mortality in Captive Asian Elephants (Elephas maximus)

Juvenile mortality is a key factor influencing population growth rate in density-independent, predation-free, well-managed captive populations. Currently at least a quarter of all Asian elephants live in captivity, but both the wild and captive populations are unsustainable with the present fertility and calf mortality rates. Despite the need for detailed data on calf mortality to manage effectively populations and to minimize the need for capture from the wild, very little is known of the causes and correlates of calf mortality in Asian elephants. Here we use the world's largest multigenerational demographic dataset on a semi-captive population of Asian elephants compiled from timber camps in Myanmar to investigate the survival of calves (n = 1020) to age five born to captive-born mothers (n = 391) between 1960 and 1999. Mortality risk varied significantly across different ages and was higher for males at any age. Maternal reproductive history was associated with large differences in both stillbirth and liveborn mortality risk: first-time mothers had a higher risk of calf loss as did mothers producing another calf soon (<3.7 years) after a previous birth, and when giving birth at older age. Stillbirth (4%) and pre-weaning mortality (25.6%) were considerably lower than those reported for zoo elephants and used in published population viability analyses. A large proportion of deaths were caused by accidents and lack of maternal milk/calf weakness which both might be partly preventable by supplementary feeding of mothers and calves and work reduction of high-risk mothers. Our results on Myanmar timber elephants with an extensive keeping system provide an important comparison to compromised survivorship reported in zoo elephants. They have implications for improving captive working elephant management systems in range countries and for refining population viability analyses with realistic parameter values in order to predict future population size of the Asian elephant

Synthesis and Biological Evaluation of 2-Methyl-4,5-Disubstituted Oxazoles as a Novel Class of Highly Potent Antitubulin Agents

Antimitotic agents that interfere with microtubule formation are one of the major classes of cytotoxic drugs for cancer treatment. Multiple 2-methyl-4-(3′,4′,5′-trimethoxyphenyl)-5-substituted oxazoles and their related 4-substituted-5-(3′,4′,5′-trimethoxyphenyl) regioisomeric derivatives designed as cis-constrained combretastatin A-4 (CA-4) analogues were synthesized and evaluated for their antiproliferative activity in vitro against a panel of cancer cell lines and, for selected highly active compounds, interaction with tubulin, cell cycle effects and in vivo potency. Both these series of compounds were characterized by the presence of a common 3′,4′,5′-trimethoxyphenyl ring at either the C-4 or C-5 position of the 2-methyloxazole ring. Compounds 4g and 4i, bearing a m-fluoro-p-methoxyphenyl or p-ethoxyphenyl moiety at the 5-position of 2-methyloxazole nucleus, respectively, exhibited the greatest antiproliferative activity, with IC50 values of 0.35-4.6 nM (4g) and 0.5–20.2 nM (4i), which are similar to those obtained with CA-4. These compounds bound to the colchicine site of tubulin and inhibited tubulin polymerization at submicromolar concentrations. Furthermore, 4i strongly induced apoptosis that follows the mitochondrial pathway. In vivo, 4i in a mouse syngeneic model demonstrated high antitumor activity which significantly reduced the tumor mass at doses ten times lower than that required for CA-4P, suggesting that 4i warrants further evaluation as a potential anticancer drug

Standardizing Operational Vector Sampling Techniques for Measuring Malaria Transmission Intensity: Evaluation of six Mosquito Collection Methods in Western Kenya.

Operational vector sampling methods lack standardization, making quantitative comparisons of malaria transmission across different settings difficult. Human landing catch (HLC) is considered the research gold standard for measuring human-mosquito contact, but is unsuitable for large-scale sampling. This study assessed mosquito catch rates of CDC light trap (CDC-LT), Ifakara tent trap (ITT), window exit trap (WET), pot resting trap (PRT), and box resting trap (BRT) relative to HLC in western Kenya to 1) identify appropriate methods for operational sampling in this region, and 2) contribute to a larger, overarching project comparing standardized evaluations of vector trapping methods across multiple countries. Mosquitoes were collected from June to July 2009 in four districts: Rarieda, Kisumu West, Nyando, and Rachuonyo. In each district, all trapping methods were rotated 10 times through three houses in a 3 × 3 Latin Square design. Anophelines were identified by morphology and females classified as fed or non-fed. Anopheles gambiae s.l. were further identified as Anopheles gambiae s.s. or Anopheles arabiensis by PCR. Relative catch rates were estimated by negative binomial regression. When data were pooled across all four districts, catch rates (relative to HLC indoor) for An. gambiae s.l (95.6% An. arabiensis, 4.4% An. gambiae s.s) were high for HLC outdoor (RR = 1.01), CDC-LT (RR = 1.18), and ITT (RR = 1.39); moderate for WET (RR = 0.52) and PRT outdoor (RR = 0.32); and low for all remaining types of resting traps (PRT indoor, BRT indoor, and BRT outdoor; RR < 0.08 for all). For Anopheles funestus, relative catch rates were high for ITT (RR = 1.21); moderate for HLC outdoor (RR = 0.47), CDC-LT (RR = 0.69), and WET (RR = 0.49); and low for all resting traps (RR < 0.02 for all). At finer geographic scales, however, efficacy of each trap type varied from district to district. ITT, CDC-LT, and WET appear to be effective methods for large-scale vector sampling in western Kenya. Ultimately, choice of collection method for operational surveillance should be driven by trap efficacy and scalability, rather than fine-scale precision with respect to HLC. When compared with recent, similar trap evaluations in Tanzania and Zambia, these data suggest that traps which actively lure host-seeking females will be most useful for surveillance in the face of declining vector densities

Competition and habitat quality influence age and sex distribution in wintering rusty blackbirds.

Bird habitat quality is often inferred from species abundance measures during the breeding and non-breeding season and used for conservation management decisions. However, during the non-breeding season age and sex classes often occupy different habitats which suggest a need for more habitat-specific data. Rusty Blackbird (Euphagus carolinus) is a forested wetland specialist wintering in bottomland hardwood forests in the south-eastern U. S. and belongs to the most steeply declining songbirds in the U.S. Little information is available to support priority birds such as the Rusty Blackbird wintering in this threatened habitat. We assessed age and sex distribution and body condition of Rusty Blackbirds among the three major habitats used by this species in the Lower Mississippi Alluvial Valley and also measured food availability. Overall, pecan groves had the highest biomass mainly driven by the amount of nuts. Invertebrate biomass was highest in forests but contributed only a small percentage to overall biomass. Age and sex classes were unevenly distributed among habitats with adult males primarily occupying pecan groves containing the highest nut biomass, females being found in forests which had the lowest nut biomass and young males primarily staying in forest fragments along creeks which had intermediate nut biomass. Males were in better body condition than females and were in slightly better condition in pecan groves. The results suggest that adult males occupy the highest quality habitat and may competitively exclude the other age and sex classes

Equity-oriented toolkit for health technology assessment and knowledge translation: application to scaling up of training and education for health workers

Human resources for health are in crisis worldwide, especially in economically disadvantaged areas and areas with high rates of HIV/AIDS in both health workers and patients. International organizations such as the Global Health Workforce Alliance have been established to address this crisis. A technical working group within the Global Health Workforce Alliance developed recommendations for scaling up education and training of health workers. The paper will illustrate how decision-makers can use evidence and tools from an equity-oriented toolkit to scale up training and education of health workers, following five recommendations of the technical working group. The Equity-Oriented Toolkit, developed by the World Health Organization Collaborating Centre for Knowledge Translation and Health Technology Assessment in Health Equity, has four major steps: (1) burden of illness; (2) community effectiveness; (3) economic evaluation; and (4) knowledge translation/implementation. Relevant tools from each of these steps will be matched with the appropriate recommendation from the technical working group

Genetics of photoreceptor degeneration and regeneration in zebrafish

Zebrafish are unique in that they provide a useful model system for studying two critically important problems in retinal neurobiology, the mechanisms responsible for triggering photoreceptor cell death and the innate stem cell–mediated regenerative response elicited by this death. In this review we highlight recent seminal findings in these two fields. We first focus on zebrafish as a model for studying photoreceptor degeneration. We summarize the genes currently known to cause photoreceptor degeneration, and we describe the phenotype of a few zebrafish mutants in detail, highlighting the usefulness of this model for studying this process. In the second section, we discuss the several different experimental paradigms that are available to study regeneration in the teleost retina. A model outlining the sequence of gene expression starting from the dedifferentiation of Müller glia to the formation of rod and cone precursors is presented

Submicroscopic Gametocytes and the Transmission of Antifolate-Resistant Plasmodium falciparum in Western Kenya

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites. In the present study, we determine the association between parasite mutations, submicroscopic P. falciparum gametocytemia and malaria transmission to mosquitoes. METHODOLOGY/PRINCIPAL FINDINGS: Samples from children treated with SP alone or in combination with artesunate (AS) or amodiaquine were genotyped for SNPs in the dhfr and dhps genes. Gametocytemia was determined by microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification (Pfs25 QT-NASBA). Transmission was determined by membrane-feeding assays. We observed no wild type infections, 66.5% (127/191) of the infections expressed mutations at all three dhfr codons prior to treatment. The presence of all three mutations was not related to higher Pfs25 QT-NASBA gametocyte prevalence or density during follow-up, compared to double mutant infections. The proportion of infected mosquitoes or oocyst burden was also not related to the number of mutations. Addition of AS to SP reduced gametocytemia and malaria transmission during follow-up. CONCLUSIONS/SIGNIFICANCE: In our study population where all infections had at least a double mutation in the dhfr gene, additional mutations were not related to increased submicroscopic gametocytemia or enhanced malaria transmission. The absence of wild-type infections is likely to have reduced our power to detect differences. Our data further support the use of ACT to reduce the transmission of drug-resistant malaria parasites