Preventing the next generation of extensively drug-resistant tuberculosis.

Multidrug-resistant and extremely drug-resistant tuberculosis strains threaten to become an intractable problem. Misuse of antibiotics and inadequacy of diagnostic tools have fostered drug resistance. Effective diagnostic technology would eliminate this problem, but it remains unavailable in high-burden areas. New drugs with novel targets may help combat drug resistance. However, if added singly to existing combination regimens, resistance will increase. To protect the efficacy of a new drug, it should first be used only as a second-line drug, in cases that have undergone drug susceptibility testing. Widespread use of new drugs as first-line agents would follow with the dawn of a new rapid diagnostic era.

Hombres violentos contra la pareja: trastornos mentales y perfiles tipológicos

Los objetivos de este artículo teórico son analizar los trastornos mentales y los déficits psicológicos más relevantes de los hombres violentos contra la pareja, así como señalar los distintos tipos de maltratadores existentes según las clasificaciones de Holtzworth-Munroe y Stuart (1994) y deFernández-Montalvo y Echeburúa (1997). Para ello se ha realizado una revisión de múltiples trabajosteóricos y empíricos. Los principales resultados indican que los agresores suelen presentar con frecuencia alteraciones psicológicas –falta de control sobre la ira, dificultades en la expresión de emociones, distorsiones cognitivas, déficits de habilidades de comunicación y de solución de problemasy baja autoestima-, y, en menor medida, cuadros clínicos bien definidos (por ejemplo, alcoholismo, trastornos de la personalidad, celos delirantes). En conclusión, existen diferentes tipos de hombres violentos -agresores limitados al ámbito familiar, agresores con características borderline/disfóricasy agresores violentos en general/antisociales- que requieren programas de tratamiento, adaptados asus características y necesidades específicas. Por último, se comentan las líneas de investigación másurgentes.

The aims of this theoretical paper are to analyze the mental disorders and the most relevant psychological deficits of intimate partner violent men, as well as to identify different types of batterers according to the classifications of Holtzworth-Munroe and Stuart (1994) and of Fernandez-Montalvo and Echeburúa (1997). A review of multiple theoretical and empirical papers has been carried out with this purpose. The main results show that the aggressors usually show psychologicaldeficits –lack of control over anger, difficulty in expressing emotions, cognitive distortions, deficit incommunication skills and problem solving, and low self-esteem-, and, not as often, well-established clinical disorders (eg, alcoholism, personality disorders, delusional jealousy). In conclusion, there are different types of violent men –family only, dysphoric/borderline and generally violent/antisocialwho require treatment programs adapted to their specific characteristics and needs. Finally, the future perspectives and the most relevant goals of research are commented on.

Os objetivos deste artigo teórico são analisar os transtornos mentais e os déficits psicológicos mais relevantes dos homens violentos contra o casal, assim como assinalar os diferentes tipos de agressores existentes segundo as classificações de Holtzworth-Munroe e Stuart (1994) e de Fernández-Montalvoe Echeburúa (1997). Para isso se realizou uma revisão de múltiplos trabalhos teóricos e empoíricos.Os principais resultados indicam que os agressores costumam apresentar com freqüência alterações psicológicas –falta de controle sobre a ira, dificuldades na expressão de emoções, distorções cognitivas, déficits de habilidades de comunicação e de solução de problemas, e baixa auto-estima-, e, em menor medida, quadros clínicos bem definidos (por exemplo, alcoolismo, transtornos da personalidade, ciúmes delirantes). Em conclusão, existem diferentes tipos de homens violentos -agressores limitadosao âmbito familiar, agressores com características “borderline/disfóricas” e agressores violentos em geral/anti-sociais- que requerem programas de tratamento adaptados a suas características e necessidades específicas. Por último, se comentam as linhas de pesquisa mais urgentes.

Immunological characterization of novel secreted antigens of Mycobacterium tuberculosis.

Proteins secreted by Mycobacterium tuberculosis are targets of host immune responses and as such are investigated for vaccine and immunodiagnostics development. Computer-driven searches of the M. tuberculosis H37Rv genome had previously identified 45 novel secreted proteins. Here, we report the characterization of these antigens in terms of specificity for the M. tuberculosis complex and the ability to induce human immune responses. BLAST homology searches and Southern hybridization identified 10 genes that were either specific for the M. tuberculosis complex or found in only two nontuberculous mycobacterial species of minor medical significance. Selected recombinant proteins were purified from Escherichia coli cells and tested for the ability to elicit antibody responses in tuberculosis patients. Reactivity of the serum panel was ' 36% with at least one of five novel proteins (Rv0203, Rv0603, Rv1271c, Rv1804c and Rv2253), 56% with the 38 kDa lipoprotein, a M. tuberculosis antigen known to be highly seroreactive, and 68% with a combination of Rv0203, Rv1271c and the 38 kDa antigen. Thus, at least five novel secreted proteins induce antibody responses during active disease; some of these proteins may increase the sensitivity of serological assays based on the 38 kDa antigen.

The involvement of poly(ADP-ribose) polymerase in the oxidative stress responses in plants.

In plants many biotic and abiotic stresses can cause secondary oxidative stress. Earlier work showed that, depending on the severity of the oxidative stress, plants can activate either cell protective genes or programmed cell death (PCD). Poly(ADP-ribose) polymerase (PARP) has been implicated as one of the enzymes in the apoptotic pathways induced by DNA damaging agents or oxidative stress. We show that in cultured soybean cells, PARP is involved in responses to mild and severe oxidative stresses, by mediating DNA repair and PCD processes, respectively. Addition of PARP inhibitors reduced the degree of cell death triggered by H2O2. Two windows of NAD consumption after H2O2 treatment were detected. Experiments with transient overexpression of Arabidopsis PARP cDNA promoted DNA repair and inhibited cell death caused by mild oxidative stress. However, following severe stress PARP overexpression increased cell death. Expression of antisense PARP produced the opposite effects: an increase in DNA nicks and inhibition of cell death at high, but not mild doses of H2O2.

A membrane-associated form of sucrose synthase and its potential role in synthesis of cellulose and callose in plants.

Sucrose synthase (SuSy; EC 2.4.1.13; sucrose + UDP reversible UDPglucose + fructose) has always been studied as a cytoplasmic enzyme in plant cells where it serves to degrade sucrose and provide carbon for respiration and synthesis of cell wall polysaccharides and starch. We report here that at least half of the total SuSy of developing cotton fibers (Gossypium hirsutum) is tightly associated with the plasma membrane. Therefore, this form of SuSy might serve to channel carbon directly from sucrose to cellulose and/or callose synthases in the plasma membrane. By using detached and permeabilized cotton fibers, we show that carbon from sucrose can be converted at high rates to both cellulose and callose. Synthesis of cellulose or callose is favored by addition of EGTA or calcium and cellobiose, respectively. These findings contrast with the traditional observation that when UDPglucose is used as substrate in vitro, callose is the major product synthesized. Immunolocalization studies show that SuSy can be localized at the fiber surface in patterns consistent with the deposition of cellulose or callose. Thus, these results support a model in which SuSy exists in a complex with the beta-glucan synthases and serves to channel carbon from sucrose to glucan.

Evidence for a cyclic diguanylic acid-dependent cellulose synthase in plants.

Because numerous attempts to detect an activity for a cellulose synthase in plants have failed, we have taken a different approach toward detecting polypeptides involved in this process. The uniqueness of the structure and function of cyclic diguanylic acid (c-di-GMP) as an activator of the cellulose synthase of the bacterium Acetobacter xylinum makes it an attractive probe to use in a search for a c-di-GMP receptor that might be involved in the process in plants. Direct photolabeling with 32P-c-di-GMP has been used, therefore, to identify in plants two membrane polypeptides of 83 and 48 kD derived from cotton fibers that possess properties consistent with their being components of a c-di-GMP-dependent cellulose synthase. Based upon several criteria, the 48-kD species is proposed to be derived by proteolytic cleavage of the 83-kD polypeptide. Both polypeptides bind c-di-GMP with high affinity and specificity and show antigenic relatedness to the bacterial cellulose synthase, and the N-terminal sequence of the 48-kD polypeptide also indicates relatedness to the bacterial synthase. Ability to detect both cotton fiber polypeptides by photolabeling increases markedly in extracts derived from fibers entering the active phase of secondary wall cellulose synthesis. These results provide a basis for future work aimed at identifying and characterizing genes involved in cellulose synthesis in plants.