Direct searches for dark matter: Recent results

There is abundant evidence for large amounts of unseen matter in the universe. This dark matter, by its very nature, couples feebly to ordinary matter and is correspondingly difficult to detect. Nonetheless, several experiments are now underway with the sensitivity required to detect directly galactic halo dark matter through their interactions with matter and radiation. These experiments divide into two broad classes: searches for weakly interacting massive particles (WIMPs) and searches for axions. There exists a very strong theoretical bias for supposing that supersymmetry (SUSY) is a correct description of nature. WIMPs are predicted by this SUSY theory and have the required properties to be dark matter. These WIMPs are detected from the byproducts of their occasional recoil against nucleons. There are efforts around the world to detect these rare recoils. The WIMP part of this overview focuses on the cryogenic dark matter search (CDMS) underway in California. Axions, another favored dark matter candidate, are predicted to arise from a minimal extension of the standard model that explains the absence of the expected large CP violating effects in strong interactions. Axions can, in the presence of a large magnetic field, turn into microwave photons. It is the slight excess of photons above noise that signals the axion. Axion searches are underway in California and Japan. The axion part of this overview focuses on the California effort. Brevity does not allow me to discuss other WIMP and axion searches, likewise for accelerator and satellite based searches; I apologize for their omission.

Novel Gq alpha isoform is a candidate transducer of rhodopsin signaling in a Drosophila testes-autonomous pacemaker.

DGq is the alpha subunit of the heterotrimeric GTPase (G alpha), which couples rhodopsin to phospholipase C in Drosophila vision. We have uncovered three duplicated exons in dgq by scanning the GenBank data base for unrecognized coding sequences. These alternative exons encode sites involved in GTPase activity and G beta-binding, NorpA (phospholipase C)-binding, and rhodopsin-binding. We examined the in vivo splicing of dgq in adult flies and find that, in all but the male gonads, only two isoforms are expressed. One, dgqA, is the original visual isoform and is expressed in eyes, ocelli, brain, and male gonads. The other, dgqB, has the three novel exons and is widely expressed. Remarkably, all three nonvisual B exons are highly similar (82% identity at the amino acid level) to the Gq alpha family consensus, from Caenorhabditis elegans to human, but all three visual A exons are divergent (61% identity). Intriguingly, we have found a third isoform, dgqC, which is specifically and abundantly expressed in male gonads, and shares the divergent rhodopsin-binding exon of dgqA. We suggest that DGqC is a candidate for the light-signal transducer of a testes-autonomous photosensory clock. This proposal is supported by the finding that rhodopsin 2 and arrestin 1, two photoreceptor-cell-specific genes, are also expressed in male gonads.

Autocrine signaling through ATP release represents a novel mechanism for cell volume regulation.

Recovery of cell volume in response to osmotic stress is mediated in part by increases in the Cl- permeability of the plasma membrane. These studies evaluate the hypothesis that ATP release and autocrine stimulation of purinergic (P2) receptors couple increases in cell volume to opening of Cl- channels. In HTC rat hepatoma cells, swelling induced by hypotonic exposure increased membrane Cl- current density to 44.8 +/- 7.1 pA/pF at -80 mV. Both the rate of volume recovery and the increase in Cl- permeability were inhibited in the presence of the ATP hydrolase apyrase (3 units/ml) or by exposure to the P2 receptor blockers suramin and Reactive Blue 2 (10-100 microM). Cell swelling also stimulated release of ATP. Hypotonic exposure increased the concentration of ATP in the effluent of perfused cells by 170 +/- 36 nM in the presence of a nucleotidase inhibitor (P < 0.01). In whole-cell recordings with ATP as the charge carrier, cell swelling increased membrane current density approximately 30-fold to 16.5 +/- 10.4 pA/pF. These findings indicate that increases in cell volume lead to efflux of ATP through opening of a conductive pathway consistent with a channel, and that extracellular ATP is required for recovery from swelling. ATP may function as an autocrine factor that couples increases in cell volume to opening of Cl- channels through stimulation of P2 receptors.

Transformation of Rat-1 fibroblasts with the v-src oncogene increases the tyrosine phosphorylation state and activity of the alpha subunit of Gq/G11.

Two major intermediaries in signal transduction pathways are pp60v-sre family tyrosine kinases and heterotrimeric guanine nucleotide-binding proteins. In Rat-1 fibroblasts transformed by the v-src oncogene, endothelin-1 (ET-1)-induced inositol 1,4,5-trisphosphate accumulation is increased 6-fold, without any increases in the numbers of ET-1 receptors or in the response to another agonist, thrombin. This ET-1 hyperresponse can be inhibited by an antibody directed against the carboxyl terminus of the Gq/G11 alpha subunit, suggesting that the Gq/G11 protein couples ET-1 receptors to phospholipase C (PLC). While v-src transformation did not increase the expression of the Gq/G11 alpha subunit, immunoblotting with anti-phosphotyrosine antibodies and phosphoamino acid analysis demonstrated that the Gq/G11 alpha subunit becomes phosphorylated on tyrosine residues in v-src-transformed cells. Moreover, when the Gq/G11 protein was extracted from control and transformed cell lines and reconstituted with exogenous PLC, AIF*4-stimulated Gq/G11 activity was markedly increased in extracts from v-src-transformed cells. Our results demonstrate that the process of v-src transformation can increase the tyrosine phosphorylation state of the Gq/G11 alpha-subunit in intact cells and that the process causes an increase in the Gq/G11 alpha-subunit's ability to stimulate PLC following activation with AIF-4.

Products of DNA mismatch repair genes mutS and mutL are required for transcription-coupled nucleotide-excision repair of the lactose operon in Escherichia coli.

To improve our understanding of the mechanism that couples nucleotide-excision repair to transcription in expressed genes, we have examined the effects of mutations in several different DNA repair genes on the removal of cyclobutane pyrimidine dimers from the individual strands of the induced lactose operon in UV-irradiated Escherichia coli. As expected, we found little repair in either strand of the lactose operon in strains with mutations in established nucleotide excision-repair genes (uvrA, uvrB, uvrC, or uvrD). In contrast, we found that mutations in either of two genes required for DNA-mismatch correction (mutS and mutL) selectively abolish rapid repair in the transcribed strand and render the cells moderately sensitive to UV irradiation. Similar results were found in a strain with a mutation in the mfd gene, the product of which has been previously shown to be required for transcription-coupled repair in vitro. Our results demonstrate an association between mismatch-correction and nucleotide-excision repair and implicate components of DNA-mismatch repair in transcription-coupled repair. In addition, they may have important consequences for human disease and may enhance our understanding of the etiology of certain cancers which have been associated with defects in mismatch correction.

Arabidopsis signal transduction mutant defective in chemically and biologically induced disease resistance.

Plants possess multiple resistance mechanisms that guard against pathogen attack. Among these are inducible systems such as systemic acquired resistance (SAR). SAR is activated by pathogen exposure and leads to an increase in salicylic acid (SA), high-level expression of SAR-related genes, and resistance to a spectrum of pathogens. To identify components of the signal transduction pathways regulating SAR, a mutant screen was developed that uses 2,6-dichloroisonicotinic acid as an activator of SAR gene expression and pathogen resistance, followed by assays for resistance to the fungal pathogen Peronospora parasitica. Mutants from this screen were subsequently examined to assess their defense responses. We describe here a recessive mutation that causes a phenotype of insensitivity to chemical and biological inducers of SAR genes and resistance. These data indicate the existence of a common signaling pathway that couples these diverse stimuli to induction of SAR genes and resistance. Because of its non-inducible immunity phenotype, we call this mutant nim1. Although nim1 plants fail to respond to SA, they retain the ability to accumulate wild-type levels of SA, a probable endogenous signal for SAR. Further, the ability of nim1 plants to support growth of normally incompatible races of a fungal pathogen indicates a role for this pathway in expression of genetically determined resistance, consistent with earlier findings for transgenic plants engineered to break down SA. These results suggest that the wild-type NIM1 gene product functions in a pathway regulating acquired resistance, at a position downstream of SA accumulation and upstream of SAR gene induction and expression of resistance.

A construção da parentalidade na interação com filhos com Síndrome de Down

No Brasil nasce uma criança com Síndrome de Down (SD) a cada 600 nascimentos, o que representa aproximadamente 8.000 bebês com SD por ano. As peculiaridades no desenvolvimento dessas crianças exigem que os pais desenvolvam habilidades especiais para contemplarem cada necessidade diferenciada da criança que poderia passar despercebida ou facilmente captada nas crianças sem nenhum tipo de Síndrome. A interação com os pais, agentes primordiais nesse processo, é essencial, inclusive, para minimizar os efeitos da Síndrome; porém pouco se tem estudado sobre a vivência dos cuidadores no encontro com a criança. Nesse contexto, objetivou-se compreender como se deu a construção do \"ser pai/mãe\" de uma criança com Síndrome de Down, desde o diagnóstico da Síndrome de Down até o momento da entrevista. Para tanto se utilizou o método clínico-qualitativo, através do estudo de caso coletivo. Como referencial teórico para análise a psicanálise winnicottiana. Realizou-se entrevistas semiabertas, individuais, face a face, com 5 casais de pais de crianças com Síndrome de Down, com idade de 7 a 10 anos. As entrevistas foram audiogravadas e transcritas na íntegra. Os resultados foram apresentados através de quatro categorias, a saber: \"Amor a segunda vista\" aborda o processo interativo inicial, os pais relatam o choque ao receber a notícia da Síndrome e os desafios na readaptação dos sonhos e expectativas. \"O ambiente lugar e não lugar\" descreve como os pais perceberam os diversos ambientes, alguns hostis que não contribuíram para que os mesmos pudessem ser acolhidos e potencializados na tarefa de cuidar desse filho, ressaltando que a ausência de suporte acarreta em sobrecarga na percepção dos pais; Por outro lado, consideram que o maior suporte que tiveram foi do parceiro, o que auxiliou na aceitação da notícia e em encontrar possibilidades de cuidado. \"Encontro Suficientemente Bom\" coloca em relevo a descrição dos participantes de que há maneiras diferentes de ajustar o cuidado na interação com seus filhos que perpassaram tanto por incômodos, quanto pela possibilidade do gesto criativo que se apresenta em atividades triviais e importantes do desenvolvimento. \"Trans-formações\" destaca às mudanças que os pais vivenciam ao poder se aproximar do filho \"real\", assumindo novos papéis, transformando-se através da abertura ao novo do outro e de si mesmos. A partir desse estudo pôde-se compreender que a relação vai se constituindo e se regulando reciprocamente, os cuidados precisam ser ajustados à demanda e possibilidade do outro. Compreendeu-se, ainda, que criatividade é a característica que permite que os pais sejam espontâneoss e recontruam significados e modos de interagir pessoais com seus filhos. Os pais entrevistados indicam que quanto mais lento e exigente o cuidado com seus filhos com Síndrome de Down, mais possibilidades de encontros surgem, e quando esses podem ser suficientemente bons, são \"trans-formadores\" para ambos: pais e filho. Ampliou-se a compreensão quanto a necessidade de acolhimento às angústias vividas, e suporte para o processo da construção da parentalidade.

Parent-Child Interaction and Children's Self-Concept

This study is designed to investigate the relationships between marital communication, the quality of parents' ability to assist their children in joint problem-solving, and children's independent mastery attempts and perceived competence at problem-solving, and behavioral indicators of self-esteem. Couples' skill at regulating their own and their children's negative affect within the marital and parent-child family subsystems is hypothesized to predict the quality of their assistance, or scaffolding behavior, to their children during joint problem-solving. Further, the quality of parental scaffolding behavior is expected to predict children's independent mastery attempts, levels of perceived competence at problemsolving, and behavioral indicators of self-esteem. Families for the study will be those with children between 3 1/2 to six years of age recruited from subjects participating in a longitudinal study of communication in marriage being conducted at the Denver Center for Marital and Family Studies. Families will participate in three interaction tasks designed to tap parental scaffolding behavior during problemsolving with their children. Children will be administered self-report measures to tap their perceived competence at such problem-solving as those in the interaction tasks and parents will complete a questionnaire tapping the behavioral indicators of their child's self-esteem. Family interaction data will be coded with the use of a microanalytic coding system developed by this study, the Parent-Child Interaction Coding System. Marital communication data at three time points, premaritally, during the transition to parenthood , and concurrently, will be obtained from couples' interactions from the longitudinal study. The clinical significance of this study includes implications for training couples how to effectively regulate negative affect and offer their children sensitive assistance during joint problem-solving.

Brief of Amici Curiae Scholars of the Constitutional Rights of Children in Support of Petitioners in Obergefell v. Hodges

Supreme Court precedent establishes that the government may not punish children for matters beyond their control. Same-sex marriage bans and non-recognition laws (“marriage bans”) do precisely this. The states argue that marriage is good for children, yet marriage bans categorically exclude an entire class of children – children of same-sex couples – from the legal, economic and social benefits of marriage. This amicus brief recounts a powerful body of equal protection jurisprudence that prohibits punishing children to reflect moral disapproval of parental conduct or to incentivize adult behavior. We then explain that marriage bans punish children of same-sex couples because they: 1) foreclose their central legal route to family formation; 2) categorically void their existing legal parent-child relationships incident to out-of-state marriages; 3) deny them economic rights and benefits; and 4) inflict psychological and stigmatic harm. States cannot justify marriage bans as good for children and then exclude children of same-sex couples based on moral disapproval of their same-sex parents’ relationships or to incentivize opposite-sex couples to “procreate” within the bounds of marriage. To do so, severs the connection between legal burdens and individual responsibility and creates a permanent class or caste distinction.

Maddening the Minotaur : Dora Maar'a power over Pablo Picasso

Dora Maar is primarily viewed as Pablo Picasso’s mistress and muse in art historical scholarship, and scholars frequently analyze her work in terms of its evolution as a consequence of her relationship with Pablo Picasso, therefore asserting the power Picasso had over Maar. Through comparative analysis and socio-historical investigation, I assert that Maar’s strong personality, political awareness, and artistic vision profoundly influenced Picasso during the Spanish Civil War and World War II.

Anomalias congénitas associadas a técnicas de reprodução medicamente assistida

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Transmissão sexual e tratamento na hepatite C aguda : dois casos clinicos

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

A Defensive "stand-by reaction" at Critical Moments of the Reproductive Life Cycle

Investigation about the psychological experiences of the reproductive life cycle showed that in critical moments special reactions may happen. These reactions seem to be defensive in nature, are set in motion in order to promote some kind of emotional protection and are performed in two opposite directions: a) a decreasing of the contact with aggressive impulses and b) an increasing of the use of rationalization and denial of frustrating situations. Examples of those rearrangements were observed at samples of: 1) pregnant women in obstetric high-risk consultation, 2) infertile couples waiting for infertility consultations and 3) pregnant women waiting for amniocentesis results. These data seem to be in accordance with the classical psychological points of view: a) gestation should be considered as a period of protection, b) during pregnancy a “primary maternal preoccupation” (Winnicot, 1958) emerges leading to the mobilization of all resources available for pregnant women and c) along gestational development psychological changes show how flexible maternal functioning may become. What was not expected is that in the absence of pregnancy, infertile couples should behave very similarly to what it is observed when pregnancy is in danger or when medical problems about the mother’s or the baby’s health arise in the horizon. Due to its “freezing” consequences upon emotional development we propose that this kind of reaction will be designated as “stand-by reaction”.

Fibrose quística : fenótipo e genótipo : descrição de caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Disfunção erétil

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014