[Rehabilitation in women with spinal cord injuries: thoughts for 8 March]. / La rehabilitación en la mujer con lesión medular: una reflexión para el 8 de marzo.

TITLE: La rehabilitación en la mujer con lesión medular: una reflexión para el 8 de marzo.

RhoBTB1 interacts with ROCKs and inhibits invasion.

RhoBTB1 is an atypical Rho GTPase with two BTB domains in addition to its Rho domain. Although most Rho GTPases regulate actin cytoskeletal dynamics, RhoBTB1 is not known to affect cell shape or motility. We report that RhoBTB1 depletion increases prostate cancer cell invasion and induces elongation in Matrigel, a phenotype similar to that induced by depletion of ROCK1 and ROCK2. We demonstrate that RhoBTB1 associates with ROCK1 and ROCK2 and its association with ROCK1 is via its Rho domain. The Rho domain binds to the coiled-coil region of ROCK1 close to its kinase domain. We identify two amino acids within the Rho domain that alter RhoBTB1 association with ROCK1. RhoBTB1 is a substrate for ROCK1, and mutation of putative phosphorylation sites reduces its association with Cullin3, a scaffold for ubiquitin ligases. We propose that RhoBTB1 suppresses cancer cell invasion through interacting with ROCKs, which in turn regulate its association with Cullin3. Via Cullin3, RhoBTB1 has the potential to affect protein degradation.

Podoplanin mediates ECM degradation by squamous carcinoma cells through control of invadopodia stability.

Invadopodia are actin-rich cell membrane projections used by invasive cells to penetrate the basement membrane. Control of invadopodia stability is critical for efficient degradation of the extracellular matrix (ECM); however, the underlying molecular mechanisms remain poorly understood. Here, we uncover a new role for podoplanin, a transmembrane glycoprotein closely associated with malignant progression of squamous cell carcinomas (SCCs), in the regulation of invadopodia-mediated matrix degradation. Podoplanin downregulation in SCC cells impairs invadopodia stability, thereby reducing the efficiency of ECM degradation. We report podoplanin as a novel component of invadopodia-associated adhesion rings, where it clusters prior to matrix degradation. Early podoplanin recruitment to invadopodia is dependent on lipid rafts, whereas ezrin/moesin proteins mediate podoplanin ring assembly. Finally, we demonstrate that podoplanin regulates invadopodia maturation by acting upstream of the ROCK-LIMK-Cofilin pathway through the control of RhoC GTPase activity. Thus, podoplanin has a key role in the regulation of invadopodia function in SCC cells, controlling the initial steps of cancer cell invasion.

Cdc42 promotes transendothelial migration of cancer cells through ß1 integrin.

Cancer cells interact with endothelial cells during the process of metastatic spreading. Here, we use a small interfering RNA screen targeting Rho GTPases in cancer cells to identify Cdc42 as a critical regulator of cancer cell-endothelial cell interactions and transendothelial migration. We find that Cdc42 regulates ß1 integrin expression at the transcriptional level via the transcription factor serum response factor (SRF). ß1 integrin is the main target for Cdc42-mediating interaction of cancer cells with endothelial cells and the underlying extracellular matrix, as exogenous ß1 integrin expression was sufficient to rescue the Cdc42-silencing phenotype. We show that Cdc42 was required in vivo for cancer cell spreading and protrusion extension along blood vessels and retention in the lungs. Interestingly, transient Cdc42 depletion was sufficient to decrease experimental lung metastases, which suggests that its role in endothelial attachment is important for metastasis. By identifying ß1 integrin as a transcriptional target of Cdc42, our results provide new insight into Cdc42 function.

Glomus tumor of the hallux. Review of the literature and report of two cases.

A glomus tumor is a rare and benign vascular tumor. It can originate in multiple locations on the body, although it has most frequently been found in subungeal areas of the hand. This two cases report describes a glomus tumor of the hallux, including a recurrence and a review of the related literature. We believe this case study might be of interest due to the unusual location of this tumor.

Mitochondrial fusion is increased by the nuclear coactivator PGC-1beta.

BACKGROUND: There is no evidence to date on whether transcriptional regulators are able to shift the balance between mitochondrial fusion and fission events through selective control of gene expression. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate that reduced mitochondrial size observed in knock-out mice for the transcriptional regulator PGC-1beta is associated with a selective reduction in Mitofusin 2 (Mfn2) expression, a mitochondrial fusion protein. This decrease in Mfn2 is specific since expression of the remaining components of mitochondrial fusion and fission machinery were not affected. Furthermore, PGC-1beta increases mitochondrial fusion and elongates mitochondrial tubules. This PGC-1beta-induced elongation specifically requires Mfn2 as this process is absent in Mfn2-ablated cells. Finally, we show that PGC-1beta increases Mfn2 promoter activity and transcription by coactivating the nuclear receptor Estrogen Related Receptor alpha (ERRalpha). CONCLUSIONS/SIGNIFICANCE: Taken together, our data reveal a novel mechanism by which mammalian cells control mitochondrial fusion. In addition, we describe a novel role of PGC-1beta in mitochondrial physiology, namely the control of mitochondrial fusion mainly through Mfn2.

Mathematical models for combined high pressure and thermal plasmin inactivation kinetics in two model systems.

The combined high-pressure thermal inactivation kinetics of plasmin was studied in 2 model systems. The first system contained both plasmin and plasminogen, whereas, in the second system, all plasminogen was converted into plasmin, with urokinase, before the inactivation studies. High-pressure treatments were conducted in the range of 300 to 800 MPa combined with temperatures from 30 to 65 degrees C. Under all conditions of pressure and temperature (isobaric-isothermal) studied, for both systems, first-order inactivation was observed. A third-degree polynomial model (derived from thermodynamic principles) successfully described the temperature and pressure dependence of the inactivation rate constant over the entire experimental domain. The antagonistic effect and the stabilization effect observed above a threshold pressure value of 600 MPa were thought to be related to the disruption of disulfide bonds in plasmin and plasminogen.

High pressure thermal inactivation kinetics of a plasmin system.

A crude plasmin extract was prepared from milk by ultracentrifugation and was partially purified using ammonium sulfate precipitation. Isothermal and high-pressure inactivation of this plasmin system at pH 6.7 could be described by a first-order kinetic model. As expected, the plasmin system displayed a high thermostability. High-pressure treatments were conducted in the 300- to 800-MPa pressure range, combined with temperatures from 25 to 65 degrees C. The plasmin system was very pressure stable at room temperature, but inactivation occurred with combined high-pressure/temperature-treatments. The influence of temperature at different constant pressures on the inactivation rate constant was quantified using the Arrhenius equation. At all temperatures studied, a synergistic effect of temperature and high pressure was observed in the 300- to 600-MPa pressure range. However, an antagonistic effect of temperature and pressure appeared at pressures above 600 MPa.

Thymo-adrenals reaction in pre-pubertal and pubertal Wistar rats in response to acute administration of calcitonin.

Pre- and post-pubertal Wistar rats were injected i.m. with a single dose equivalent to 1 UI of Calcitonin (Calsyn-50 Rorer, Swiss). Its effects upon the thymus and adrenals were assessed after 1, 3 and respectively, 8 days since injection. The results pointed to differences of reaction of the thymus and adrenals dependent on rat ages and on the period of hormone persistence in the organism. The effects in mature rats are characterized by a stress state, reflected in adrenal reaction, but without impact upon the thymus in point of biochemical parameters. In rats of that age, modifications in both organs are much reduced after 8 days since calcitonin injection. In pubertal rats, adrenal activity is temperate, and thymus registers modification of DNA, of oxygen consumption and of nitrogen aminic after 3 days since injection. This modification is maintained for 8 days.

Alcoholic liver diseases in Portugal. Clinical and laboratory picture, mortality, and survival.

Six main types of histopathological changes were found in 463 patients with chronic alcoholism admitted during the 10-year period from 1966 to 1975: group I, normal liver in 2.6%; group II, fatty liver in 8.4%; group III, acute alcoholic hepatitis (AAH) in 7.6%; group IV, cirrhosis with or without steatosis in 68.7%; group V, cirrhosis with AAH in 12.8%; group VI, liver cell carcinoma (LCC) in 1.9% (all of the latter patients were also included in group IV). Seventy-three % were males and 27% were females. Females tended to be older than males. Cirrhosis was found in 68% of the group between 21 and 30 yr and in 85% between 51 and 60 yr. Normal histology or steatosis was less frequent after the age of 50 yr. Ascites and jaundice were more frequent in patients with AAH than in patients with steatosis. The majority of patients had SGOT under 100 karmen units/ml; SGPT was normal in 80% of patients with cirrhosis and higher than 100 karmen units/ml in 10%. SGPT was higher than SGOT in only 11.9% of the patients. Mortality was 46.7% according to the followup until 1978. Survival was 38.4% at the end of the first year and decreased very slowly afterwards to 32.8% in males and 11.5% in females after a 5-yr period.