Macrostructural Alterations of Subcortical Grey Matter in Psychogenic Erectile Dysfunction

Psychogenic erectile dysfunction (ED) has been defined as the persistent inability to attain and maintain an erection sufficient to permit sexual performance. It shows a high incidence and prevalence among men, with a significant impact on the quality of life. Few neuroimaging studies have investigated the cerebral basis of erectile dysfunctions observing the role played by prefrontal, cingulate, and parietal cortices during erotic stimulation. In spite of the well-known involvement of subcortical regions such as hypothalamus and caudate nucleus in male sexual response, and the key role of nucleus accumbens in pleasure and reward, poor attention was paid to their role in male sexual dysfunction. In this study, we determined the presence of grey matter (GM) atrophy patterns in subcortical structures such as amygdala, hippocampus, nucleus accumbens, caudate nucleus, putamen, pallidum, thalamus, and hypothalamus in patients with psychogenic ED and healthy men. After Rigiscan evaluation, urological, general medical, metabolic and hormonal, psychological and psychiatric assessment, 17 outpatients with psychogenic ED and 25 healthy controls were recruited for structural MRI session. Significant GM atrophy of nucleus accumbens was observed bilaterally in patients with respect to controls. Shape analysis showed that this atrophy was located in the left medial-anterior and posterior portion of accumbens. Left nucleus accumbens volumes in patients correlated with low erectile functioning as measured by IIEF-5 (International Index of Erectile Function). In addition, a GM atrophy of left hypothalamus was also observed. Our results suggest that atrophy of nucleus accumbens plays an important role in psychogenic erectile dysfunction. We believe that this change can influence the motivation-related component of sexual behavior. Our findings help to elucidate a neural basis of psychogenic erectile dysfunction

Interplay between cell adhesion and growth factor receptors: from the plasma membrane to the endosomes

The emergence of multicellular animals could only take place once evolution had produced molecular mechanisms for cell adhesion and communication. Today, all metazoans express integrin-type adhesion receptors and receptors for growth factors. Integrins recognize extracellular matrix proteins and respective receptors on other cells and, following ligand binding, can activate the same cellular signaling pathways that are regulated by growth factor receptors. Recent reports have indicated that the two receptor systems also collaborate in many other ways. Here, we review the present information concerning the role of integrins as assisting growth factor receptors and the interplay between the receptors in cell signaling and in the orchestration of receptor recycling

The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin.

International audienceMannan-binding lectin (MBL), ficolins and collectin-11 are known to associate with three homologous modular proteases, the MBL-Associated Serine Proteases (MASPs). The crystal structures of the catalytic domains of MASP-1 and MASP-2 have been solved, but the structure of the corresponding domain of MASP-3 remains unknown. A link between mutations in the MASP1/3 gene and the rare autosomal recessive 3MC (Mingarelli, Malpuech, Michels and Carnevale,) syndrome, characterized by various developmental disorders, was discovered recently, revealing an unexpected important role of MASP-3 in early developmental processes. To gain a first insight into the enzymatic and structural properties of MASP-3, a recombinant form of its serine protease (SP) domain was produced and characterized. The amidolytic activity of this domain on fluorescent peptidyl-aminomethylcoumarin substrates was shown to be considerably lower than that of other members of the C1r/C1s/MASP family. The E. coli protease inhibitor ecotin bound to the SP domains of MASP-3 and MASP-2, whereas no significant interaction was detected with MASP-1, C1r and C1s. A tetrameric complex comprising an ecotin dimer and two MASP-3 SP domains was isolated and its crystal structure was solved and refined to 3.2 Å. Analysis of the ecotin/MASP-3 interfaces allows a better understanding of the differential reactivity of the C1r/C1s/MASP protease family members towards ecotin, and comparison of the MASP-3 SP domain structure with those of other trypsin-like proteases yields novel hypotheses accounting for its zymogen-like properties in vitro

High-level integration of murine intestinal transcriptomics data highlights the importance of the complement system in mucosal homeostasis.

BACKGROUND: The mammalian intestine is a complex biological system that exhibits functional plasticity in its response to diverse stimuli to maintain homeostasis. To improve our understanding of this plasticity, we performed a high-level data integration of 14 whole-genome transcriptomics datasets from samples of intestinal mouse mucosa. We used the tool Centrality based Pathway Analysis (CePa), along with information from the Reactome database. RESULTS: The results show an integrated response of the mouse intestinal mucosa to challenges with agents introduced orally that were expected to perturb homeostasis. We observed that a common set of pathways respond to different stimuli, of which the most reactive was the Regulation of Complement Cascade pathway. Altered expression of the Regulation of Complement Cascade pathway was verified in mouse organoids challenged with different stimuli in vitro. CONCLUSIONS: Results of the integrated transcriptomics analysis and data driven experiment suggest an important role of epithelial production of complement and host complement defence factors in the maintenance of homeostasis

Tight junctions: from simple barriers to multifunctional molecular gates

Epithelia and endothelia separate different tissue compartments and protect multicellular organisms from the outside world. This requires the formation of tight junctions, selective gates that control paracellular diffusion of ions and solutes. Tight junctions also form the border between the apical and basolateral plasma-membrane domains and are linked to the machinery that controls apicobasal polarization. Additionally, signalling networks that guide diverse cell behaviours and functions are connected to tight junctions, transmitting information to and from the cytoskeleton, nucleus and different cell adhesion complexes. Recent advances have broadened our understanding of the molecular architecture and cellular functions of tight junctions

Iterative synthesis of oligo[n]rotaxanes in excellent yield

We present an operationally simple iterative coupling strategy for the synthesis of oligomeric homo- and hetero[n]rotaxanes with precise control over the position of each macrocycle. The exceptional yield of the AT-CuAAC reaction, combined with optimized conditions that allow the rapid synthesis of the target oligomers, opens the door to the study of precision-engineered oligomeric interlocked molecules

Sobrevida después de accidentes de tránsito: impacto de las variables clínicas y pre hospitalarias

OBJETIVO: Analisar as variáveis clínicas e pré-hospitalares associadas à sobrevivência de vítimas de acidente de trânsito. MÉTODOS: Estudo realizado no município de São Paulo, SP, de 1999 a 2003. Foram analisados dados de 175 pacientes, entre 12 e 65 anos, vitimados por acidente de trânsito. A Análise de Sobrevivência de Kaplan-Meier foi utilizada na abordagem dos resultados na cena do acidente com as vítimas de escore <11 segundo o Revised Trauma Score. As variáveis analisadas foram: sexo, idade, mecanismos do acidente, procedimentos de suporte básico e avançado realizados, parâmetros e flutuações do Revised Trauma Score, tempo consumido na fase pré-hospitalar e gravidade do trauma segundo o Injury Severity Score e a Maximum Abbreviated Injury Scale. RESULTADOS: A análise identificou que as vítimas que tiveram menor probabilidade de sobrevivência durante todo período de internação hospitalar apresentaram: lesões graves no abdome, tórax ou membros inferiores, com flutuação negativa da freqüência respiratória e do Revised Trauma Score na fase pré-hospitalar e necessitaram de intervenções avançadas ou compressões torácicas. As lesões encefálicas foram associadas ao óbito tardio. CONCLUSÕES: O reconhecimento das variáveis envolvidas na sobrevivência de vítimas de acidentes de trânsito pode auxiliar na determinação de protocolos e na tomada de decisão para a realização de intervenções pré e intra-hospitalares e conseqüentemente maximizar a sobrevivência.OBJECTIVE: To assess clinical and prehospital variables associated with survival of motor vehicle crash victims. METHODS: Study carried out in the city of São Paulo (Southeastern Brazil), from 1999 to 2003. Data from 175 patients, who were aged between 12 and 65 years and had been motor vehicle crash victims, were analyzed. Kaplan-Meier Survival Analysis was used to approach the results at the accident scene with victims scoring <11, according to the Revised Trauma Score. Variables analyzed were: sex, age, injury mechanisms, basic and advanced support procedures, Revised Trauma Score parameters and fluctuations, time elapsed in the prehospital phase and trauma severity according to the Injury Severity Score and Maximum Abbreviated Injury Scale. RESULTS: Analysis revealed that victims who were less likely to survive during the hospitalization period showed serious lesions in the abdomen, thorax, or lower limbs, with negative fluctuation of respiratory frequency and Revised Trauma Score in the prehospital phase. In addition, they needed specialized interventions or thoracic compressions. Brain lesions were associated with late death. CONCLUSIONS: Recognition of variables involved in the survival of motor vehicle crash victims may help to determine protocols and to make decisions in order to perform pre- and in-hospital interventions and, consequently, maximize survival.OBJETIVO: Analizar las variables clínicas y pre hospitalarias asociadas a la sobrevida de víctimas de accidentes del tránsito. MÉTODOS: Estudio realizado en el municipio de São Paulo (Sudeste de Brasil), de 1999 a 2003. Fueron analizados datos de 175 pacientes, entre 12 y 65 años, victimas de accidentes de tránsito. El análisis de Sobrevida de Kaplan-Meier fue utilizado en el abordaje de los resultados en la escena del accidente con las víctimas de score <11 segun el Revised Trauma Score. Las variables analizadas fueron: sexo, edad, mecanismos del accidente, procedimientos de soporte básico y avanzado realizados, parámetros y fluctuaciones del Revised Trauma Score, tiempo consumido en la fase pre hospitalaria y gravedad del trauma según el Injury Severity Score y la Maximum Abbreviated Injury Scale. RESULTADOS: El análisis identificó que la víctimas que tuvieron menor probabilidad de sobre vivencia durante todo el período de interacción hospitalaria presentaron: lesiones graves en el abdomen, tórax o miembros inferiores, con fluctuación negativa de la frecuencia respiratoria y del Revised Trauma Score en la fase pre hospitalaria y necesitaron de intervenciones avanzadas o compresiones torácicas. Las lesiones encefálicas fueron asociadas al óbito tardío. CONCLUSIONES: El reconocimiento de las variables involucradas en la sobrevida de víctimas de accidentes del tránsito puede auxiliar en la determinación de protocolos y en la toma de decisiones para la realización de intervenciones pre e intra-hospitalarias y consecuentemente maximizar la sobrevida