The loss of female sex pheromone after mating in the corn earworm moth Helicoverpa zea: identification of a male pheromonostatic peptide.

Female moths often become depleted of sex pheromone after mating as the various components of virgin behavior are switched off. In examining a potential male contribution to these events in the corn earworm moth Helicoverpa zea, we have characterized a basic polypeptide from the tissues producing (accessory glands) and storing (duplex) the seminal fluids. The peptide evokes the depletion of sex pheromone when injected into virgin females. This pheromonostatic peptide (PSP) is 57 amino acids long and contains a single disulfide bridge. It is blocked at the N terminus with pyroglutamate and at the C terminus by amidation. As little as 23 ng of peptide evokes the near-complete depletion of pheromone in decapitated (neck-ligated) females that had been injected with pheromone biosynthesis-activating neuropeptide. Activity is approximately 15-fold less in intact virgins, showing that the head limits the expression of activity in these injected females. Females mated to surgically impaired males, capable of producing a spermatophore but not transferring spermatozoa or seminal fluids, are depleted of pheromone by injected peptide. Females whose abdominal nerve cords have been severed are not depleted of pheromone after mating. Thus, neural signals either descending or ascending via the nerve cord are required for the depletion of pheromone after mating. PSP, from the seminal fluids, may participate in this process by direct or indirect action on the glandular tissue; if so, it represents an unusual mechanism in insects for the regulation by seminal fluids of postmating reproductive behavior.

Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene.

Mutations in the APC (adenomatous polyposis coli) gene appear to be responsible for not only familial adenomatous polyposis but also many sporadic cases of gastrointestinal cancers. Using homologous recombination in mouse embryonic stem cells, we constructed mice that contained a mutant gene encoding a product truncated at a 716 (Apc delta 716). Mendelian transmission of the gene caused most homozygous mice to die in utero before day 8 of gestation. The heterozygotes developed multiple polyps throughout the intestinal tract, mostly in the small intestine. The earliest polyps arose multifocally during the third week after birth, and new polyps continued to appear thereafter. Surprisingly, every nascent polyp consisted of a microadenoma covered with a layer of the normal villous epithelium. These microadenomas originated from single crypts by forming abnormal outpockets into the inner (lacteal) side of the neighboring villi. We carefully dissected such microadenomas from nascent polyps by peeling off the normal epithelium and determined their genotype by PCR: all microadenomas had already lost the wild-type Apc allele, whereas the mutant allele remained unchanged. These results indicate that loss of heterozygosity followed by formation of intravillous microadenomas is responsible for polyposis in Apc delta 716 intestinal mucosa. It is therefore unlikely that the truncated product interacts directly with the wild-type protein and causes the microadenomas by a dominant negative mechanism.

In vivo estradiol-dependent dephosphorylation of the repressor MDBP-2-H1 correlates with the loss of in vitro preferential binding to methylated DNA.

We have previously shown that estradiol treatment of roosters resulted in a rapid loss of binding activity of the repressor MDBP-2-H1 (a member of the histone H1 family) to methylated DNA that was not due to a decrease in MDBP-2-H1 concentration. Here we demonstrate that MDBP-2-H1 from rooster liver nuclear extracts is a phosphoprotein. Phosphoamino acid analysis reveals that the phosphorylation occurs exclusively on serine residues. Two-dimensional gel electrophoresis and tryptic phosphopeptide analysis show that MDBP-2-H1 is phosphorylated at several sites. Treatment of roosters with estradiol triggers a dephosphorylation of at least two sites in the protein. Phosphatase treatment of purified rooster MDBP-2-H1 combined with gel mobility shift assay indicates that phosphorylation of MDBP-2-H1 is essential for the binding to methylated DNA and that the dephosphorylation can occur on the protein bound to methylated DNA causing its release from DNA. Thus, these results suggest that in vivo modification of the phosphorylation status of MDBP-2-H1 caused by estradiol treatment may be a key step for the down regulation of its binding to methylated DNA.

Loss of the catalytic subunit of the DNA-dependent protein kinase in DNA double-strand-break-repair mutant mammalian cells.

The DNA-dependent protein kinase (DNA-PK) consists of three polypeptide components: Ku-70, Ku-80, and an approximately 350-kDa catalytic subunit (p350). The gene encoding the Ku-80 subunit is identical to the x-ray-sensitive group 5 complementing gene XRCC5. Expression of the Ku-80 cDNA rescues both DNA double-strand break (DSB) repair and V(D)J recombination in group 5 mutant cells. The involvement of Ku-80 in these processes suggests that the underlying defect in these mutant cells may be disruption of the DNA-PK holoenzyme. In this report we show that the p350 kinase subunit is deleted in cells derived from the severe combined immunodeficiency mouse and in the Chinese hamster ovary cell line V-3, both of which are defective in DSB repair and V(D)J recombination. A centromeric fragment of human chromosome 8 that complements the scid defect also restores p350 protein expression and rescues in vitro DNA-PK activity. These data suggest the scid gene may encode the p350 protein or regulate its expression and are consistent with a model whereby DNA-PK is a critical component of the DSB-repair pathway.

Mutation of juxtamembrane tyrosine residue 1001 suppresses loss-of-function mutations of the met receptor in epithelial cells.

Signals transduced by the met tyrosine kinase, which is the receptor for scatter factor/hepatocyte growth factor, are of major importance for the regulation of epithelial cell motility, morphogenesis, and proliferation. We report here that different sets of tyrosine residues in the cytoplasmic domain of the met receptor affect signal transduction in epithelial cells in a positive or negative fashion: mutation of the C-terminal tyrosine residues 13-16 (Y1311, Y1347, Y1354, and Y1363) reduced or abolished ligand-induced cell motility and branching morphogenesis. In contrast, mutation of the juxtamembrane tyrosine residue 2 (Y1001) produced constitutively mobile, fibroblastoid cells. Furthermore, the gain-of-function mutation of tyrosine residue 2 suppressed the loss-of-function mutations of tyrosine residue 15 or 16. The opposite roles of the juxtamembrane and C-terminal tyrosine residues may explain the suggested dual function of the met receptor in both epithelial-mesenchymal interactions and tumor progression.

I'm Not Who I Thought I Was: A Contextual Resolution to the Identity Loss of Combat PTSD.

Given the historical rates of combat post-traumatic stress disorder (PTSD), one can expect 30% of soldiers returning from current military conflicts to suffer from PTSD. For these individuals, various cognitive behavioral therapies (CBT) are the most commonly employed treatments. Unfortunately, however, symptom relapse can be expected with the various CBT approaches, as traumatic memories remain. Soldiers are imbued with a militarized identity, and the identity loss experienced by those soldiers who suffer from PTSD is particularly painful for this population, as the militarized identity effectively disavows personal suffering. For this reason, many combat veterans diagnosed with post-traumatic stress disorder experience undue, prolonged suffering as they struggle to make sense of the different person they fear they have become. This paper contrasts certain versions of Western philosophy, which view the self as a fixed and reified entity with certain versions of Eastern philosophy, which view the self as more contextual and fluid, in order to illuminate the value of employing third wave behavioral treatments, specifically Acceptance and Commitment Therapy (ACT), to treat the identity loss experienced by military veterans with PTSD. ACT echoes the Buddhist principle that attachment to verbally-constructed conceptual notions of self contribute to undue suffering, and that more vital living can be achieved by assuming a more contextual and experiential perspective on identity. Research and anecdotal accounts are cited to illustrate why treatment for identity loss associated with combat PTSD should be less focused on reconstructing a historically substance-oriented self and more focused on an epistemological reorientation to a deconstructed, contextual self.

Otimização acústica e análise numérica do escoamento ao redor de um conjunto cilindro-placa separadora.

RESUMO Simulações de aeroacústica computacional demandam uma quantidade considerável de tempo, o que torna complicada a realização de estudos paramétricos. O presente trabalho propõe uma metodologia viável para otimização aeroacústica. Através da análise numérica utilizando dinâmica dos fluidos computacional, foi estudada a aplicação de uma placa separadora desacoplada como método de controle passivo da esteira turbulenta de um cilindro e avaliou-se a irradiação de ruído causado pela interação do escoamento com ambos os corpos, empregando ferramentas de aeroacústica computacional baseadas no método de Ffowcs-Williams e Hawkings. Algumas abordagens distintas de metodologias de otimização de projeto foram aplicadas neste problema, com o objetivo de chegar a uma configuração otimizada que permita a redução do nível sonoro ao longe. Assim, utilizando uma ferramenta de otimização multidisciplinar, pode-se avaliar a capacidade de modelos heurísticos e a grande vantagem do emprego de algoritmos baseados em método de superfície de resposta quando aplicados em um problema não linear, pois requerem a avaliação de um menor número de alternativas para se obter um ponto ótimo. Além disso, foi possível identificar e agrupar os resultados em 5 clusters baseados em seus parâmetros geométricos, nível de pressão sonora global e o valor quadrático médio do coeficiente de arrasto, confirmando a eficiência da aplicação de placas separadoras longas desacopladas posicionadas próximas ao cilindro na estabilização da esteira turbulenta, enquanto que o posicionamento de placas acima de um espaçamento crítico aumentou o nível de pressão acústica irradiado devido à formação de vórtices no espaço entre o cilindro e a placa separadora.

Loss of Outer Retinal Neurons and Circuitry Alterations in the DBA/2J Mouse

Purpose. The DBA/2J mouse line develops essential iris atrophy, pigment dispersion, and glaucomatous age-related changes, including an increase of IOP, optic nerve atrophy, and retinal ganglion cell (RGC) death. The aim of this study was to evaluate possible morphological changes in the outer retina of the DBA/2J mouse concomitant with disease progression and aging, based on the reduction of both the a- and b-waves and photopic flicker ERGs in this mouse line. Methods. Vertically sectioned DBA/2J mice retinas were evaluated at 3, 8, and 16 months of age using photoreceptor, horizontal, and bipolar cell markers. Sixteen-month-old C57BL/6 mice retinas were used as controls. Results. The DBA/2J mice had outer retinal degeneration at all ages, with the most severe degeneration in the oldest retinas. At 3 months of age, the number of photoreceptor cells and the thickness of the OPL were reduced. In addition, there was a loss of horizontal and ON-bipolar cell processes. At 8 months of age, RGC degeneration occurred in patches, and in the outer retina overlying these patches, cone morphology was impaired with a reduction in size as well as loss of outer segments and growth of horizontal and bipolar cell processes into the outer nuclear layer. At 16 months of age, connectivity between photoreceptors and horizontal and bipolar cell processes overlying these patches was lost. Conclusions. Retinal degeneration in DBA/2J mice includes photoreceptor death, loss of bipolar and horizontal cell processes, and loss of synaptic contacts in an aging-dependent manner.

Fixed Mydriatic Pupil Associated with an Intraocular Pressure Rise as a Complication of the Implant of a Phakic Refractive Lens (PRL)

We describe a case report of a patient that was implanted with a posterior chamber phakic intraocular lens (Phakic Refractive Lens, PRL) for the correction of moderate myopia and who developed postoperatively a fixed mydriasis compatible with an Urrets-Zavalia Syndrome (UZS). Specifically, a sudden acute increase of IOP in the left eye was observed in the immediate postoperative period. After IOP stabilization, the refractive result was good, but a fixed and mydriatic pupil appeared. This condition led the patient to experience visual discomfort, halos, and glare associated with high levels of higher-order aberrations in spite of the good visual result. A tinted-contact lens was fitted in order to minimize those symptoms. The UZS should be considered as a possible complication after implantation of posterior chamber phakic intraocular lenses.

Health inequality between immigrants and natives in Spain: the loss of the healthy immigrant effect in times of economic crisis

Background: The immigrant population living in Spain grew exponentially in the early 2000s but has been particularly affected by the economic crisis. This study aims to analyse health inequalities between immigrants born in middle- or low-income countries and natives in Spain, in 2006 and 2012, taking into account gender, year of arrival and socioeconomic exposures. Methods: Study of trends using two cross-sections, the 2006 and 2012 editions of the Spanish National Health Survey, including residents in Spain aged 15–64 years (20 810 natives and 2950 immigrants in 2006, 14 291 natives and 2448 immigrants in 2012). Fair/poor self-rated health, poor mental health (GHQ-12 > 2), chronic activity limitation and use of psychotropic drugs were compared between natives and immigrants who arrived in Spain before 2006, adjusting robust Poisson regression models for age and socioeconomic variables to obtain prevalence ratios (PR) and 95% confidence interval (CI). Results: Inequalities in poor self-rated health between immigrants and natives tend to increase among women (age-adjusted PR2006 = 1.39; 95% CI: 1.24–1.56, PR2012 = 1.56; 95% CI: 1.33–1.82). Among men, there is a new onset of inequalities in poor mental health (PR2006 = 1.10; 95% CI: 0.86–1.40, PR2012 = 1.34; 95% CI: 1.06–1.69) and an equalization of the previously lower use of psychotropic drugs (PR2006 = 0.22; 95% CI: 0.11–0.43, PR2012 = 1.20; 95% CI: 0.73–2.01). Conclusions: Between 2006 and 2012, immigrants who arrived in Spain before 2006 appeared to worsen their health status when compared with natives. The loss of the healthy immigrant effect in the context of a worse impact of the economic crisis on immigrants appears as potential explanation. Employment, social protection and re-universalization of healthcare would prevent further deterioration of immigrants’ health status.