The prevalence of onchocerciasis in Africa and Yemen, 2000-2018: a geospatial analysis.

BACKGROUND: Onchocerciasis is a disease caused by infection with Onchocerca volvulus, which is transmitted to humans via the bite of several species of black fly, and is responsible for permanent blindness or vision loss, as well as severe skin disease. Predominantly endemic in parts of Africa and Yemen, preventive chemotherapy with mass drug administration of ivermectin is the primary intervention recommended for the elimination of its transmission. METHODS: A dataset of 18,116 geo-referenced prevalence survey datapoints was used to model annual 2000-2018 infection prevalence in Africa and Yemen. Using Bayesian model-based geostatistics, we generated spatially continuous estimates of all-age 2000-2018 onchocerciasis infection prevalence at the 5 × 5-km resolution as well as aggregations to the national level, along with corresponding estimates of the uncertainty in these predictions. RESULTS: As of 2018, the prevalence of onchocerciasis infection continues to be concentrated across central and western Africa, with the highest mean estimates at the national level in Ghana (12.2%, 95% uncertainty interval [UI] 5.0-22.7). Mean estimates exceed 5% infection prevalence at the national level for Cameroon, Central African Republic, Democratic Republic of the Congo (DRC), Guinea-Bissau, Sierra Leone, and South Sudan. CONCLUSIONS: Our analysis suggests that onchocerciasis infection has declined over the last two decades throughout western and central Africa. Focal areas of Angola, Cameroon, the Democratic Republic of the Congo, Ethiopia, Ghana, Guinea, Mali, Nigeria, South Sudan, and Uganda continue to have mean microfiladermia prevalence estimates exceeding 25%. At and above this level, the continuation or initiation of mass drug administration with ivermectin is supported. If national programs aim to eliminate onchocerciasis infection, additional surveillance or supervision of areas of predicted high prevalence would be warranted to ensure sufficiently high coverage of program interventions.

Molecular phylogenetics and diversification of trap-jaw ants in the genera Anochetus and Odontomachus (Hymenoptera: Formicidae).

Ants in the genera Anochetus and Odontomachus belong to one of the largest clades in the subfamily Ponerinae, and are one of four lineages of ants possessing spring-loaded "trap-jaws." Here we present results from the first global species-level molecular phylogenetic analysis of these trap-jaw ants, reconstructed from one mitochondrial, one ribosomal RNA, and three nuclear protein-coding genes. Bayesian and likelihood analyses strongly support reciprocal monophyly for the genera Anochetus and Odontomachus. Additionally, we found strong support for seven trap-jaw ant clades (four in Anochetus and three in Odontomachus) mostly concordant with geographic distribution. Ambiguity remains concerning the closest living non-trap-jaw ant relative of the Anochetus+Odontomachus clade, but Bayes factor hypothesis testing strongly suggests that trap-jaw ants evolved from a short mandible ancestor. Ponerine trap-jaw ants originated in the early Eocene (52.5Mya) in either South America or Southeast Asia, where they have radiated rapidly in the last 30million years, and subsequently dispersed multiple times to Africa and Australia. These results will guide future taxonomic work on the group and act as a phylogenetic framework to study the macroevolution of extreme ant mouthpart specialization.

Thyroid hormones alter the transcriptome of in vitro-produced bovine blastocysts.

Thyroid hormones (THs) have been shown to improve in vitro embryo production in cattle by increasing blastocyst formation rate, and the average cell number of blastocysts and by significantly decreasing apoptosis rate. To better understand those genetic aspects that may underlie enhanced early embryo development in the presence of THs, we characterized the bovine embryonic transcriptome at the blastocyst stage, and examined differential gene expression profiles using a bovine-specific microarray. We found that 1212 genes were differentially expressed in TH-treated embryos when compared with non-treated controls (>1.5-fold at P < 0.05). In addition 23 and eight genes were expressed uniquely in control and treated embryos, respectively. The expression of genes specifically associated with metabolism, mitochondrial function, cell differentiation and development were elevated. However, TH-related genes, including those encoding TH receptors and deiodinases, were not differentially expressed in treated embryos. Furthermore, the over-expression of 52 X-chromosome linked genes in treated embryos suggested a delay or escape from X-inactivation. This study highlights the significant impact of THs on differential gene expression in the early embryo; the identification of TH-responsive genes provides an insight into those regulatory pathways activated during development.

Advances in the REDCAT software package.

BACKGROUND: Residual Dipolar Couplings (RDCs) have emerged in the past two decades as an informative source of experimental restraints for the study of structure and dynamics of biological macromolecules and complexes. The REDCAT software package was previously introduced for the analysis of molecular structures using RDC data. Here we report additional features that have been included in this software package in order to expand the scope of its analyses. We first discuss the features that enhance REDCATs user-friendly nature, such as the integration of a number of analyses into one single operation and enabling convenient examination of a structural ensemble in order to identify the most suitable structure. We then describe the new features which expand the scope of RDC analyses, performing exercises that utilize both synthetic and experimental data to illustrate and evaluate different features with regard to structure refinement and structure validation. RESULTS: We establish the seamless interaction that takes place between REDCAT, VMD, and Xplor-NIH in demonstrations that utilize our newly developed REDCAT-VMD and XplorGUI interfaces. These modules enable visualization of RDC analysis results on the molecular structure displayed in VMD and refinement of structures with Xplor-NIH, respectively. We also highlight REDCAT's Error-Analysis feature in reporting the localized fitness of a structure to RDC data, which provides a more effective means of recognizing local structural anomalies. This allows for structurally sound regions of a molecule to be identified, and for any refinement efforts to be focused solely on locally distorted regions. CONCLUSIONS: The newly engineered REDCAT software package, which is available for download via the WWW from http://ifestos.cse.sc.edu, has been developed in the Object Oriented C++ environment. Our most recent enhancements to REDCAT serve to provide a more complete RDC analysis suite, while also accommodating a more user-friendly experience, and will be of great interest to the community of researchers and developers since it hides the complications of software development.

Molecular phylogenetics of ponerine ants (Hymenoptera: Formicidae: Ponerinae).

Recent molecular phylogenetic studies of ants (Hymenoptera: Formicidae) have revolutionized our understanding of how these ecologically dominant organisms diversified, but detailed phylogenies are lacking for most major ant subfamilies. I report the results of the first detailed phylogenetic study of the ant subfamily Ponerinae, a diverse cosmopolitan lineage whose properties make it an attractive model system for investigating social and ecological evolution in ants. Molecular sequence data were obtained from four nuclear genes (wingless, long-wavelength rhodopsin, rudimentary [CAD], 28S rDNA; total of ~3.3 kb) for 86 ponerine taxa, representing all three ponerine tribes, 22 of the 28 currently recognized genera, and 14 of the 18 informal subgenera of Pachycondyla, a heterogeneous grouping whose monophyly is doubtful on morphological grounds. Phylogenetic reconstructions using maximum likelihood and Bayesian inference support the monophyly of Ponerinae and tribe Platythyreini, but fail to support the monophyly of the large tribe Ponerini due to its inclusion of the unusual genus Thaumatomyrmex. Pachycondyla is inferred to be broadly non-monophyletic. Numerous novel generic and suprageneric relationships are inferred within Ponerini, which was found to consist of four major multi-generic clades (the Ponera, Pachycondyla, Plectroctena and Odontomachus genus groups) plus the single genera Hypoponera and Harpegnathos. Uncertainty remains in some regions of the phylogeny, including at the base of Ponerini, possibly reflecting rapid radiation. Divergence dating using a Bayesian relaxed clock method estimates an origin for stem Ponerinae in the upper Cretaceous, a major burst of diversification near the K/T boundary, and a rich and continual history of diversification during the Cenozoic. These results fail to support the predictions of the "dynastic-succession hypothesis" previously developed to explain the high species diversity of Ponerinae. Though model-based reconstructions of historical biogeography and trait evolution were not attempted in this study, the phylogeny suggests that ponerine evolution was marked by regionalized radiations and frequent faunal exchange between major biogeographic provinces. The reported results also imply multiple origins of cryptobiotic foraging, mass raiding behavior, and gamergate reproduction within Ponerinae, highlighting the value of the subfamily as a model for studying the incipient evolution of these and other ecological and behavioral traits.

Differences in Longevity and Temperature-Driven Extrinsic Incubation Period Correlate with Varying Dengue Risk in the Arizona-Sonora Desert Region.

Dengue transmission is determined by a complex set of interactions between the environment, Aedes aegypti mosquitoes, dengue viruses, and humans. Emergence in new geographic areas can be unpredictable, with some regions having established mosquito populations for decades without locally acquired transmission. Key factors such as mosquito longevity, temperature-driven extrinsic incubation period (EIP), and vector-human contact can strongly influence the potential for disease transmission. To assess how these factors interact at the edge of the geographical range of dengue virus transmission, we conducted mosquito sampling in multiple urban areas located throughout the Arizona-Sonora desert region during the summer rainy seasons from 2013 to 2015. Mosquito population age structure, reflecting mosquito survivorship, was measured using a combination of parity analysis and relative gene expression of an age-related gene, SCP-1. Bloodmeal analysis was conducted on field collected blood-fed mosquitoes. Site-specific temperature was used to estimate the EIP, and this predicted EIP combined with mosquito age were combined to estimate the abundance of "potential" vectors (i.e., mosquitoes old enough to survive the EIP). Comparisons were made across cities by month and year. The dengue endemic cities Hermosillo and Ciudad Obregon, both in the state of Sonora, Mexico, had higher abundance of potential vectors than non-endemic Nogales, Sonora, Mexico. Interestingly, Tucson, Arizona consistently had a higher estimated abundance of potential vectors than dengue endemic regions of Sonora, Mexico. There were no observed city-level differences in species composition of blood meals. Combined, these data offer insights into the critical factors required for dengue transmission at the ecological edge of the mosquito's range. However, further research is needed to integrate an understanding of how social and additional environmental factors constrain and enhance dengue transmission in emerging regions.

Predicting the environmental suitability for onchocerciasis in Africa as an aid to elimination planning.

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify.

Fulminant infectious mononucleosis and recurrent Epstein-Barr virus reactivation in an adolescent.

We describe a unique case of fulminant infectious mononucleosis and recurrent Epstein-Barr virus reactivation presenting in an adolescent. Detailed assays of Epstein-Barr virus-specific T cell immunity revealed defects in the patient's T cell receptor signalling pathway characterized by a lack of interleukin-2 and CD25 expression, which may have contributed to her clinical course. Allogeneic stem cell transplantation reversed the clinical and laboratory phenotype.

Thyroid hormone supplementation improves bovine embryo development in vitro.

BACKGROUND: Early embryo development (EED) forms the basis of assisted reproductive technologies (ARTs), which are used to treat human infertility and to propagate other mammalian species. Thyroid hormones (THs) play an important role in the post-implantation development of the embryo in mammals; however, the effects of THs on pre-attachment embryos are not known. Currently utilized in-vitro embryo production media are devoid of THs and hence our main objective was to examine whether THs affected EED in a bovine model. METHODS: To determine if THs are present at the site of fertilization and EED in cattle, we evaluated the presence of the hormones in oviductal and uterine horn tissues. To assess the outcome of free TH supplementation (50 ng/ml of each hormone: triiodothyronine-T3 and thyroxin-T4), embryos were followed through standard and TH-supplemented in-vitro procedures, and evaluated for the cleavage rates, blastocyst formation rate and hatching rates. Embryo quality was assessed using TUNEL assay and post-cryopreservation survival was also evaluated. RESULTS: Although TH levels in in-vitro culture media were found to be approximately 60% of the administered doses, the TH-treated embryos exhibited significant increases in blastocyst formation and hatching rates (P < 0.05). Embryo quality was significantly improved in the treated groups as demonstrated by greater total cell counts and reduced proportions of apoptotic cells (P < 0.05). Finally, TH supplementation was associated with improved post-cryopreservation viability, defined by blastocyst re-expansion and hatching rates after frozen embryos had been thawed and cultured (P < 0.05). CONCLUSIONS: These findings not only provide a way of optimizing ART efficiency, but also further our understanding of how THs influence embryonic development in mammals.

Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours.

Uveal melanoma (UM) is the most common intraocular tumour in adults and despite surgical or radiation treatment of primary tumours, ~50% of patients progress to metastatic disease. Therapeutic options for metastatic UM are limited, with clinical trials having little impact. Here we perform whole-genome sequencing (WGS) of 103 UM from all sites of the uveal tract (choroid, ciliary body, iris). While most UM have low tumour mutation burden (TMB), two subsets with high TMB are seen; one driven by germline MBD4 mutation, and another by ultraviolet radiation (UVR) exposure, which is restricted to iris UM. All but one tumour have a known UM driver gene mutation (GNAQ, GNA11, BAP1, PLCB4, CYSLTR2, SF3B1, EIF1AX). We identify three other significantly mutated genes (TP53, RPL5 and CENPE).

Breast cancer stem cells: implications for therapy of breast cancer.

The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatment. Recent improvements in immunotherapy targeting of tumour-associated antigens have advanced the prospect of targeting breast cancer stem cells, an approach that might lead to more meaningful clinical remissions. Here, we review the role of stem cells in the healthy breast, the role of breast cancer stem cells in disease, and the potential to target these cells.

Results of a phase I dendritic cell vaccine trial for malignant astrocytoma: potential interaction with adjuvant chemotherapy.

Dendritic cell vaccination has been applied to the treatment of a variety of cancers, including malignant astrocytoma. We have treated 13 patients with malignant astrocytoma using dendritic cell vaccination and have shown that this treatment is safe and is likely to be effective in combination with standard adjuvant therapy. Future studies should prospectively incorporate dendritic cell vaccination together with chemotherapy. Ideally, dendritic cell vaccination should be tested in a prospective fashion, in a coordinated trial involving multiple centres.

Effects of desiccation stress on adult female longevity in Aedes aegypti and Ae. albopictus (Diptera: Culicidae): results of a systematic review and pooled survival analysis.

BACKGROUND: Transmission dynamics of mosquito-borne viruses such as dengue, Zika and chikungunya are affected by the longevity of the adult female mosquito. Environmental conditions influence the survival of adult female Aedes mosquitoes, the primary vectors of these viruses. While the association of temperature with Aedes mortality has been relatively well-explored, the role of humidity is less established. The current study's goals were to compile knowledge of the influence of humidity on adult survival in the important vector species Aedes aegypti and Ae. albopictus, and to quantify this relationship while accounting for the modifying effect of temperature. METHODS: We performed a systematic literature review to identify studies reporting experimental results informing the relationships among temperature, humidity and adult survival in Ae. aegypti and Ae. albopictus. Using a novel simulation approach to harmonize disparate survival data, we conducted pooled survival analyses via stratified and mixed effects Cox regression to estimate temperature-dependent associations between humidity and mortality risk for these species across a broad range of temperatures and vapor pressure deficits. RESULTS: After screening 1517 articles, 17 studies (one in semi-field and 16 in laboratory settings) met inclusion criteria and collectively reported results for 192 survival experiments. We review and synthesize relevant findings from these studies. Our stratified model estimated a strong temperature-dependent association of humidity with mortality in both species, though associations were not significant for Ae. albopictus in the mixed effects model. Lowest mortality risks were estimated around 27.5 °C and 21.5 °C for Ae. aegypti and Ae. albopictus, respectively, and mortality increased non-linearly with decreasing humidity. Aedes aegypti had a survival advantage relative to Ae. albopictus in the stratified model under most conditions, but species differences were not significant in the mixed effects model. CONCLUSIONS: Humidity is associated with mortality risk in adult female Ae. aegypti in controlled settings. Data are limited at low humidities, temperature extremes, and for Ae. albopictus, and further studies should be conducted to reduce model uncertainty in these contexts. Desiccation is likely an important factor in Aedes population dynamics and viral transmission in arid regions. Models of Aedes-borne virus transmission may be improved by more comprehensively representing humidity effects.

User Participation and Engagement With the See Me Smoke-Free mHealth App: Prospective Feasibility Trial.

BACKGROUND: The See Me Smoke-Free (SMSF) mobile health (mHealth) app was developed to help women quit smoking by targeting concerns about body weight, body image, and self-efficacy through cognitive behavioral techniques and guided imagery audio files addressing smoking, diet, and physical activity. A feasibility trial found associations between SMSF usage and positive treatment outcomes. This paper reports a detailed exploration of program use among eligible individuals consenting to study participation and completing the baseline survey (participants) and ineligible or nonconsenting app installers (nonparticipants), as well as the relationship between program use and treatment outcomes. OBJECTIVE: The aim of this study was to determine whether (1) participants were more likely to set quit dates, be current smokers, and report higher levels of smoking at baseline than nonparticipants; (2) participants opened the app and listened to audio files more frequently than nonparticipants; and (3) participants with more app usage had a higher likelihood of self-reported smoking abstinence at follow up. METHODS: The SMSF feasibility trial was a single arm, within-subjects, prospective cohort study with assessments at baseline and 30 and 90 days post enrollment. The SMSF app was deployed on the Google Play Store for download, and basic profile characteristics were obtained for all app installers. Additional variables were assessed for study participants. Participants were prompted to use the app daily during study participation. Crude differences in baseline characteristics between trial participants and nonparticipants were evaluated using t tests (continuous variables) and Fisher exact tests (categorical variables). Exact Poisson tests were used to assess group-level differences in mean usage rates over the full study period using aggregate Google Analytics data on participation and usage. Negative binomial regression models were used to estimate associations of app usage with participant baseline characteristics after adjustment for putative confounders. Associations between app usage and self-reported smoking abstinence were assessed using separate logistic regression models for each outcome measure. RESULTS: Participants (n=151) were more likely than nonparticipants (n=96) to report female gender (P<.02) and smoking in the 30 days before enrollment (P<.001). Participants and nonparticipants opened the app and updated quit dates at the same average rate (rate ratio [RR] 0.98; 95% CI 0.92-1.04; P=.43), but participants started audio files (RR 1.07; 95% CI 1.00-1.13; P<.04) and completed audio files (RR 1.11; 95% CI 1.03-1.18; P<.003) at significantly higher rates than nonparticipants. Higher app usage among participants was positively associated with some smoking cessation outcomes. CONCLUSIONS: This study suggests potential efficacy of the SMSF app, as increased usage was generally associated with higher self-reported smoking abstinence. A planned randomized controlled trial will assess the SMSF app's efficacy as an intervention tool to help women quit smoking.

Genomic estimation of complex traits reveals ancient maize adaptation to temperate North America.

By 4000 years ago, people had introduced maize to the southwestern United States; full agriculture was established quickly in the lowland deserts but delayed in the temperate highlands for 2000 years. We test if the earliest upland maize was adapted for early flowering, a characteristic of modern temperate maize. We sequenced fifteen 1900-year-old maize cobs from Turkey Pen Shelter in the temperate Southwest. Indirectly validated genomic models predicted that Turkey Pen maize was marginally adapted with respect to flowering, as well as short, tillering, and segregating for yellow kernel color. Temperate adaptation drove modern population differentiation and was selected in situ from ancient standing variation. Validated prediction of polygenic traits improves our understanding of ancient phenotypes and the dynamics of environmental adaptation.

The key role of CD40 ligand in overcoming tumor-induced dendritic cell dysfunction.

Overcoming dendritic cell (DC) dysfunction is a prerequisite for successful active immunotherapy against breast cancer. CD40 ligand (CD40L), a key molecule in the interface between T-lymphocytes and DCs, seems to be instrumental in achieving that goal. Commenting on our data that CD40L protects circulating DCs from apoptosis induced by breast tumor products, Lenahan and Avigan highlighted the potential of CD40L for immunotherapy. We expand on that argument by pointing to additional findings that CD40L not only rescues genuine DCs but also functionally improves populations of immature antigen-presenting cells that fill the DC compartment in patients with breast cancer.

Spontaneous apoptosis of blood dendritic cells in patients with breast cancer.

INTRODUCTION: Dendritic cells (DCs) are key antigen-presenting cells that play an essential role in initiating and directing cellular and humoral immunity, including anti-tumor responses. Due to their critical role in cancer, induction of DC apoptosis may be one of the central mechanisms used by tumors to evade immune recognition. METHODS: Spontaneous apoptosis of blood DCs (lineage negative HLA-DR positive cells) was assessed in peripheral blood mononuclear cells (PBMCs) using Annexin-V and TUNEL assays immediately after blood collection. The role of tumor products was assessed by culturing cells with supernatants derived from breast cancer cell lines (TDSN) or PBMCs (PBMC-SN, as a control). The capacity of DC stimulation to prevent apoptosis was assessed by incubating DC with inflammatory cytokines, poly I:C, IL-12 or CD40 ligand (CD40L) prior to culture with TDSN. Apoptosis was determined by flow cytometry and microscopy, and Bcl-2 expression determined by intracellular staining. RESULTS: In this study we document the presence of a significantly higher proportion of apoptotic (Annexin-V+ and TUNEL+) blood DCs in patients with early stage breast cancer (stage I to II; n = 13) compared to healthy volunteers (n = 15). We examined the role of tumor products in this phenomenon and show that supernatants derived from breast cancer lines induce apoptosis of blood DCs in PBMC cultures. Aiming to identify factors that protect blood DC from apoptosis, we compared a range of clinically available maturation stimuli, including inflammatory cytokines (tumor necrosis factor-alpha, IL-1beta, IL-6 and prostaglandin (PG)E2 as a cytokine cocktail), synthetic double-stranded RNA (poly I:C) and soluble CD40 ligand. Although inflammatory cytokines and poly I:C induced robust phenotypic maturation, they failed to protect blood DCs from apoptosis. In contrast, CD40 stimulation induced strong antigen uptake, secretion of IL-12 and protected blood DCs from apoptosis through sustained expression of Bcl-2. Exogenous IL-12 provided similar Bcl-2 mediated protection, suggesting that CD40L effect is mediated, at least in part, through IL-12 secretion. CONCLUSION: Cumulatively, our results demonstrate spontaneous apoptosis of blood DCs in patients with breast cancer and confirm that ex vivo conditioning of blood DCs can protect them from tumor-induced apoptosis.

An extraordinarily high level of IL-15 expression by a cell line transduced with a modified BMGneo vector displays hypoxic upregulation.

Interleukin (IL)-15 expression level is tightly controlled in mammalian cells by various mechanisms. In order to achieve higher expression levels of IL-15, many attempts have been made, but the highest expression rate among those reported is still only 13.3 ng/106 cells/24 h. Here we report that a selected human embryonic kidney 293 (HEK293) cell line, denoted 293HAN cells, which can survive and proliferate under conditions of hypoxia, acidity, and nutritional depletion (HAN), after transduction -- with a modified BMGneo vector -- can produce functional human IL-15 at the extremely high rate of 890 ng/106 cells/24 h under normoxic conditions -- a 67-fold increase. This is as a result of multiple episomally based vector copy numbers per cell. An extra benefit was that the BMGneo vector was found to be inducible in hypoxia and allowed a further approximately threefold upregulation of the human IL-15 level which made these 293HAN cells, transduced with the modified BMGneo vector, a very promising tool for high IL-15 production (approximately 200-fold increase above that of baseline normoxia). The mechanism of hypoxic upregulation was found to be related to the mouse MT-1 promoter present in the vector.

On the Seasonal Occurrence and Abundance of the Zika Virus Vector Mosquito Aedes Aegypti in the Contiguous United States.

INTRODUCTION: An ongoing Zika virus pandemic in Latin America and the Caribbean has raised concerns that travel-related introduction of Zika virus could initiate local transmission in the United States (U.S.) by its primary vector, the mosquito Aedes aegypti. METHODS: We employed meteorologically driven models for 2006-2015 to simulate the potential seasonal abundance of adult Aedes aegypti for fifty cities within or near the margins of its known U.S. range. Mosquito abundance results were analyzed alongside travel and socioeconomic factors that are proxies of viral introduction and vulnerability to human-vector contact.     RESULTS: Meteorological conditions are largely unsuitable for Aedes aegypti over the U.S. during winter months (December-March), except in southern Florida and south Texas where comparatively warm conditions can sustain low-to-moderate potential mosquito abundance. Meteorological conditions are suitable for Aedes aegypti across all fifty cities during peak summer months (July-September), though the mosquito has not been documented in all cities. Simulations indicate the highest mosquito abundance occurs in the Southeast and south Texas where locally acquired cases of Aedes-transmitted viruses have been reported previously. Cities in southern Florida and south Texas are at the nexus of high seasonal suitability for Aedes aegypti and strong potential for travel-related virus introduction. Higher poverty rates in cities along the U.S.-Mexico border may correlate with factors that increase human exposure to Aedes aegypti.     DISCUSSION: Our results can inform baseline risk for local Zika virus transmission in the U.S. and the optimal timing of vector control activities, and underscore the need for enhanced surveillance for Aedes mosquitoes and Aedes-transmitted viruses.

Microarray expression profiling in melanoma reveals a BRAF mutation signature.

We have used microarray gene expression profiling and machine learning to predict the presence of BRAF mutations in a panel of 61 melanoma cell lines. The BRAF gene was found to be mutated in 42 samples (69%) and intragenic mutations of the NRAS gene were detected in seven samples (11%). No cell line carried mutations of both genes. Using support vector machines, we have built a classifier that differentiates between melanoma cell lines based on BRAF mutation status. As few as 83 genes are able to discriminate between BRAF mutant and BRAF wild-type samples with clear separation observed using hierarchical clustering. Multidimensional scaling was used to visualize the relationship between a BRAF mutation signature and that of a generalized mitogen-activated protein kinase (MAPK) activation (either BRAF or NRAS mutation) in the context of the discriminating gene list. We observed that samples carrying NRAS mutations lie somewhere between those with or without BRAF mutations. These observations suggest that there are gene-specific mutation signals in addition to a common MAPK activation that result from the pleiotropic effects of either BRAF or NRAS on other signaling pathways, leading to measurably different transcriptional changes.