The mosquito Anopheles gambiae is the principal Afrotropical vector for human malaria. A central component of its vectorial capacity is the ability to maintain sufficient populations of adults. During both adult and preadult (larval) stages, the mosquitoes depend on the ability to recognize and respond to chemical cues that mediate feeding and survival. In this study, we used a behavioral assay to identify a range of odorant-specific responses of An. gambiae larvae that are dependent on the integrity of the larval antennae. Parallel molecular analyses have identified a subset of the An. gambiae odorant receptors (AgOrs) that are localized to discrete neurons within the larval antennae and facilitate odor-evoked responses in Xenopus oocytes that are consistent with the larval behavioral spectrum. These studies shed light on chemosensory-driven behaviors and represent molecular and cellular characterization of olfactory processes in mosquito larvae. These advances may ultimately enhance the development of vector control strategies, targeting olfactory pathways in larval-stage mosquitoes to reduce the catastrophic effects of malaria and other diseases.malaria ͉ olfaction ͉ signal transduction ͉ odorant receptors S ensitivity and the ability to respond to a wide range of olfactory cues are essential for many behavioral processes that mediate the vectorial capacity of Anopheles gambiae and other diseasecarrying mosquitoes (1). Although there is a growing body of knowledge of the adult An. gambiae olfactory system, there is a paucity of information as to the molecular and cellular basis of olfaction in larval stages, in which it may be of potential importance in disease control. Paradoxically, despite being one of the historically most successful strategies for mosquito control (2) and prevention of human malaria, the targeting of mosquito larvae or larval habitats around human dwellings is sparsely implemented in Africa and other malaria-endemic regions (3). Furthermore, the simplicity of insect larval olfactory systems makes them excellent models to study olfactory signal transduction and coding. Indeed, the arbovirus vector mosquito Aedes aegypti expresses 24 odorant receptor (OR) genes in the larval antenna, 15 of which are larval specific (4). Elegant work in the Drosophila melanogaster model has detailed larval behavioral responses and characterized 25 ORs that are expressed in 21 olfactory receptor neurons (ORNs) in each of the two dorsal organs, which constitute the olfactory apparatus of the fly larva (5-7).In this study, we designed and used a simple olfactory-based assay to carry out an initial characterization of An. gambiae larval behavioral responses to a range of natural and synthetic chemical stimuli. Consistent with olfactory function, ablation of the larval antennae specifically eliminated these behavioral responses, and molecular approaches identified a set of larval AgOrs, which were in some cases larval specific and the transcripts of which were mapped to a distinctive population of ORNs within th...

BACKGROUND: Atypical teratoid rhabdoid tumor (ATRT) is a rare central nervous system malignancy with a poor prognosis that affects mostly young children. Although radiotherapy (RT) historically has been delayed in patients aged <3 years, emerging evidence suggests a role for RT to achieve long-term survivorship. Clinical features and age-dependent trends of RT use were evaluated for patients with ATRT. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify 144 patients with ATRT from 1973 to 2008. The primary endpoint was median overall survival (OS). Clinical and treatment variables were assessed for an association with OS using Cox proportional hazards models. Landmark analysis was used to correct for immortal time bias of adjuvant RT. RESULTS: The median age at diagnosis was 1 year (range, 0-67 years). Gross total resection of the primary tumor was achieved in 39% of patients, and 33% of patients received RT. From 1992 to 2008, RT use increased 2.4-fold in patients aged 3 years. The median OS for was 10 months. In multivariate analyses, metastatic disease (hazard ratio, 2.83; 95% confidence interval, 1.53-5.23; P ¼ .001) and RT (hazard ratio, 0.10; 95% confidence interval, 0.01-0.73; P ¼ .02) were identified as independent predictors of survival. Landmark analysis confirmed a robust association between RT use and survival, which was attenuated in patients ages 4 to 17 years compared with younger patients. CONCLUSIONS: The current results indicated that RT may offer a significant survival benefit for patients with ATRT and that patients aged 3 years may derive more benefit from initial RT compared with older children. The authors concluded that prospective clinical trials are needed to examine the role of RT in the initial management of ATRT in patients aged <3 years. Cancer 2012;118:4212-9. V C 2011 American Cancer Society.KEYWORDS: atypical teratoid rhabdoid tumor, central nervous system, epidemiology, radiotherapy, children. INTRODUCTIONAtypical teratoid rhabdoid tumor (ATRT) of the central nervous system (CNS) is a highly malignant embryonal neoplasm (grade 4 according to the World Health Organization classification) that typically occurs in children aged <3 years. 1-5 ATRT is extremely rare in adults, and only 31 patients have been reported in the literature. 6 Originally described in the 1980s, ATRT has been widely recognized as a rare but important clinical entity only over the past decade. 2,4 The diagnosis of ATRT has been greatly facilitated by the rise in accessibility of immunohistochemical testing in the late 1990s, which takes advantage of the frequent loss of switch/sucrose nonfermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1 (SMARCB1) (also known as SNF5 homolog [hSNF5] and INI1) tumor suppressor gene products in these tumors. 2,5,7 Although ATRT comprises <5% of CNS tumors in children aged <18 years, it reportedly represents up to 20% of CNS tumors in children aged <3 years...

Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs) mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg) or vehicle (0.09% NaCl) i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2–4 cups of coffee in humans. After dams gave birth, offspring were examined at 8–10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs) within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation.

AimsTo assess parental attitudes towards type 1 diabetes clinical trials (T1DCTs) and factors that impact willingness to enroll their children with and without diabetes.MethodsA cross-sectional survey of parents of children with type 1 diabetes was administered at an academic clinic and a diabetes educational event.ResultsSurvey response rate was 36%. Of 166 participating parents, 76% were aware of T1DCTs. More parents reported willingness to enroll children with diabetes (47%) than unaffected children (36%). Only 18% recalled being asked to enroll their children, and of these, 60% agreed to enroll at least some of those times. Less than 30% were comfortable with placebos. Factors predicting willingness to enroll children with diabetes included healthcare provider trust, comfort with consent by proxy, low fear of child being a “guinea pig,” and comfort with placebo. Factors predicting willingness to enroll unaffected children were provider trust, comfort with consent by proxy, comfort with placebo, and perceived ease of understanding T1DCT information.ConclusionsParents report moderate willingness to enroll children in T1DCTs. Willingness is diminished by common trial methodologies. Although most parents recalled receiving trial-related information, significantly fewer recalled being asked to participate. Efforts to optimize effective communication around identified areas of parental concern may increase T1DCT participation.

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