Behavioral Responses of a Parasitoid Fly to Rapidly Evolving Host Signals

Animals eavesdrop on signals and cues generated by prey, predators, hosts, parasites, competing species, and conspecifics, and the conspicuousness of sexual signals makes them particularly susceptible. Yet, when sexual signals evolve, most attention is paid to impacts on intended receivers (potential mates) rather than fitness consequences for eavesdroppers. Using the rapidly evolving interaction between the Pacific field cricket, Teleogryllus oceanicus, and the parasitoid fly, Ormia ochracea, we asked how parasitoids initially respond to novel changes in host signals. We recently discovered a novel sexual signal, purring song, in Hawaiian populations of T. oceanicus that appears to have evolved because it protects the cricket from the parasitoid while still allowing males to attract female crickets for mating. In Hawaii, there are no known alternative hosts for the parasitoid, so we would expect flies to be under selection to detect and attend to the new purring song. We used complementary field and laboratory phonotaxis experiments to test fly responses to purring songs that varied in many dimensions, as well as to ancestral song. We found that flies strongly prefer ancestral song over purring songs in both the field and the lab, but we caught more flies to purring songs in the field than reported in previous work, indicating that flies may be exerting some selective pressure on the novel song. When played at realistic amplitudes, we found no preferences–flies responded equally to all purrs that varied in frequency, broadbandedness, and temporal measures. However, our lab experiment did reveal the first evidence of preference for purring song amplitude, as flies were more attracted to purrs played at amplitudes greater than naturally occurring purring songs. As purring becomes more common throughout Hawaii, flies that can use purring song to locate hosts should be favored by selection and increase in frequency

Efficacy and safety of flexible-dose oral sildenafil citrate (Viagra((R))) in the treatment of erectile dysfunction in Brazilian and Mexican men

A 12-week, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of flexible-dose sildenafil citrate (Viagra((R))) treatment (25, 50 or 100 mg) in Brazilian and Mexican men with erectile dysfunction (ED) of broad-spectrum etiology. Efficacy was assessed on the basis of responses to the 15-item International Index of Erectile Function (IIEF) questionnaire, completed at baseline and after 12 weeks of treatment. At end point, mean scores for all IIEF domains of sexual function (erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction) were significantly (P < 0.0001) higher in the sildenafil group (n = 109) than in the placebo group (n = 105). These findings confirm the significant increases in frequency of penetration and frequency of maintained erections reported previously. Sildenafil treatment was well tolerated. the most common adverse events were headache and flushing. in conclusion, sildenafil is a well-tolerated and effective treatment for ED of broad-spectrum etiology in Latin American men.Hosp Albert Einstein, BR-01250000 São Paulo, BrazilTorre Hosp Angeles del Pedregal, Consultorio 827, MexicoFac Ciencias Med Santa Casa, Porto Alegre, RS, BrazilHosp Clin Cuiritiba, Curitiba, Parana, BrazilUniv Estadual Campinas, Fac Ciencias Med, Campinas, SP, BrazilClin Rio Claro, Rio Claro, SP, BrazilUniv Estadual Rio de Janeiro, Fac Med, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilHosp Servidor Publ Estadual, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilWeb of Scienc

Functional analysis of Ectodysplasin-A mutations causing selective tooth agenesis.

Mutations of the Ectodysplasin-A (EDA) gene are generally associated with the syndrome hypohidrotic ectodermal dysplasia (MIM 305100), but they can also manifest as selective, non-syndromic tooth agenesis (MIM300606). We have performed an in vitro functional analysis of six selective tooth agenesis-causing EDA mutations (one novel and five known) that are located in the C-terminal tumor necrosis factor homology domain of the protein. Our study reveals that expression, receptor binding or signaling capability of the mutant EDA1 proteins is only impaired in contrast to syndrome-causing mutations, which we have previously shown to abolish EDA1 expression, receptor binding or signaling. Our results support a model in which the development of the human dentition, especially of anterior teeth, requires the highest level of EDA-receptor signaling, whereas other ectodermal appendages, including posterior teeth, have less stringent requirements and form normally in response to EDA mutations with reduced activity

PUF60 variants cause a syndrome of ID, short stature, microcephaly, coloboma, craniofacial, cardiac, renal and spinal features.

PUF60 encodes a nucleic acid-binding protein, a component of multimeric complexes regulating RNA splicing and transcription. In 2013, patients with microdeletions of chromosome 8q24.3 including PUF60 were found to have developmental delay, microcephaly, craniofacial, renal and cardiac defects. Very similar phenotypes have been described in six patients with variants in PUF60, suggesting that it underlies the syndrome. We report 12 additional patients with PUF60 variants who were ascertained using exome sequencing: six through the Deciphering Developmental Disorders Study and six through similar projects. Detailed phenotypic analysis of all patients was undertaken. All 12 patients had de novo heterozygous PUF60 variants on exome analysis, each confirmed by Sanger sequencing: four frameshift variants resulting in premature stop codons, three missense variants that clustered within the RNA recognition motif of PUF60 and five essential splice-site (ESS) variant. Analysis of cDNA from a fibroblast cell line derived from one of the patients with an ESS variants revealed aberrant splicing. The consistent feature was developmental delay and most patients had short stature. The phenotypic variability was striking; however, we observed similarities including spinal segmentation anomalies, congenital heart disease, ocular colobomata, hand anomalies and (in two patients) unilateral renal agenesis/horseshoe kidney. Characteristic facial features included micrognathia, a thin upper lip and long philtrum, narrow almond-shaped palpebral fissures, synophrys, flared eyebrows and facial hypertrichosis. Heterozygote loss-of-function variants in PUF60 cause a phenotype comprising growth/developmental delay and craniofacial, cardiac, renal, ocular and spinal anomalies, adding to disorders of human development resulting from aberrant RNA processing/spliceosomal function

Further clinical and molecular delineation of the 15q24 microdeletion syndrome

Background Chromosome 15q24 microdeletion syndrome is a rare genomic disorder characterised by intellectual disability, growth retardation, unusual facial morphology and other anomalies. To date, 20 patients have been reported; 18 have had detailed breakpoint analysis. Aim To further delineate the features of the 15q24 microdeletion syndrome, the clinical and molecular characterisation of fifteen patients with deletions in the 15q24 region was performed, nearly doubling the number of reported patients. Methods Breakpoints were characterised using a custom, high-density array comparative hybridisation platform, and detailed phenotype information was collected for each patient. Results Nine distinct deletions with different breakpoints ranging in size from 266 kb to 3.75 Mb were identified. The majority of breakpoints lie within segmental duplication (SD) blocks. Low sequence identity and large intervals of unique sequence between SD blocks likely contribute to the rarity of 15q24 deletions, which occur 8-10 times less frequently than 1q21 or 15q13 microdeletions in our series. Two small, atypical deletions were identified within the region that help delineate the critical region for the core phenotype in the 15q24 microdeletion syndrome. Conclusion The molecular characterisation of these patients suggests that the core cognitive features of the 15q24 microdeletion syndrome, including developmental delays and severe speech problems, are largely due to deletion of genes in a 1.1-Mb critical region. However, genes just distal to the critical region also play an important role in cognition and in the development of characteristic facial features associated with 15q24 deletions. Clearly, deletions in the 15q24 region are variable in size and extent. Knowledge of the breakpoints and size of deletion combined with the natural history and medical problems of our patients provide insights that will inform management guidelines. Based on common phenotypic features, all patients with 15q24 microdeletions should receive a thorough neurodevelopmental evaluation, physical, occupational and speech therapies, and regular audiologic and ophthalmologic screenin

Mechanisms of Assortative Mating in Speciation with Gene Flow: Connecting Theory and Empirical Research

The large body of theory on speciation with gene flow has brought to light fundamental differences in the effects of two types of mating rules on speciation: preference/trait rules, in which divergence in both (female) preferences and (male) mating traits is necessary for assortment, and matching rules, in which individuals mate with like individuals on the basis of the presence of traits or alleles that they have in common. These rules can emerge from a variety of behavioral or other mechanisms in ways that are not always obvious. We discuss the theoretical properties of both types of rules and explain why speciation is generally thought to be more likely under matching rather than preference/trait rules. We furthermore discuss whether specific assortative mating mechanisms fall under a preference/trait or matching rule, present empirical evidence for these mechanisms, and propose empirical tests that could distinguish between them. The synthesis of the theoretical literature on these assortative mating rules with empirical studies of the mechanisms by which they act can provide important insights into the occurrence of speciation with gene flow. Finally, by providing a clear framework we hope to inspire greater alignment in the ways that both theoreticians and empiricists study mating rules and how these rules affect speciation through maintaining or eroding barriers to gene flow among closely related species or populations

Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844–848

Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000–3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distinct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense mutation affecting one of five neighboring NF1 codons—Leu844, Cys845, Ala846, Leu847, and Gly848—located in the cysteine-serine-rich domain (CSRD). Collectively, these recurrent missense mutations affect ∼0.8% of unrelated NF1 mutation-positive probands in the University of Alabama at Birmingham (UAB) cohort. Major superficial plexiform neurofibromas and symptomatic spinal neurofibromas were more prevalent in these individuals compared with classic NF1-affected cohorts (both p < 0.0001). Nearly half of the individuals had symptomatic or asymptomatic optic pathway gliomas and/or skeletal abnormalities. Additionally, variants in this region seem to confer a high predisposition to develop malignancies compared with the general NF1-affected population (p = 0.0061). Our results demonstrate that these NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation. A genotype-phenotype correlation at the NF1 region 844–848 exists and will be valuable in the management and genetic counseling of a significant number of individuals

Role of deficits in pathogen recognition receptors in infection susceptibility

This work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014 to A.C. and SFRH/BPD/96176/2013 to C.C.