Cleavage and activation of LIM kinase 1 as a novel mechanism for calpain 2-mediated regulation of nuclear dynamics.

Calpain-2 (CAPN2) is a processing enzyme ubiquitously expressed in mammalian tissues whose pleiotropic functions depend on the role played by its cleaved-products. Nuclear interaction networks, crucial for a number of molecular processes, could be modified by CAPN2 activity. However, CAPN2 functions in cell nucleus are poorly understood. To unveil CAPN2 functions in this compartment, the result of CAPN2-mediated interactions in cell nuclei was studied in breast cancer cell (BCC) lines. CAPN2 abundance was found to be determinant for its nucleolar localization during interphase. Those CAPN2-dependent components of nucleolar proteome, including the actin-severing protein cofilin-1 (CFL1), were identified by proteomic approaches. CAPN2 binding, cleavage and activation of LIM Kinase-1 (LIMK1), followed by CFL1 phosphorylation was studied. Upon CAPN2-depletion, full-length LIMK1 levels increased and CFL1/LIMK1 binding was inhibited. In addition, LIMK1 accumulated at the cell periphery and perinucleolar region and, the mitosis-specific increase of CFL1 phosphorylation and localization was altered, leading to aberrant mitosis and cell multinucleation. These findings uncover a mechanism for the role of CAPN2 during mitosis, unveil the critical role of CAPN2 in the interactions among nuclear components and, identifying LIMK1 as a new CAPN2-target, provide a novel mechanism for LIMK1 activation. CFL1 is crucial for cytoskeleton remodeling and mitosis, but also for the maintenance of nuclear structure, the movement of chromosomes and the modulation of transcription frequently altered in cancer cells. Consequently, the role of CAPN2 in the nuclear compartment might be extended to other actin-associated biological and pathological processes.

Reliability of the MDi Psoriasis® Application to Aid Therapeutic Decision-Making in Psoriasis. / Fiabilidad de una aplicación de ayuda a la toma de decisiones terapéuticas en el paciente con psoriasis (MDi Psoriasis®).

BACKGROUND: Therapeutic decisions in psoriasis are influenced by disease factors (e.g., severity or location), comorbidity, and demographic and clinical features. OBJECTIVE: We aimed to assess the reliability of a mobile telephone application (MDi-Psoriasis) designed to help the dermatologist make decisions on how to treat patients with moderate to severe psoriasis. METHOD: We analyzed interobserver agreement between the advice given by an expert panel and the recommendations of the MDi-Psoriasis application in 10 complex cases of moderate to severe psoriasis. The experts were asked their opinion on which treatments were most appropriate, possible, or inappropriate. Data from the same 10 cases were entered into the MDi-Psoriasis application. Agreement was analyzed in 3 ways: paired interobserver concordance (Cohen's κ), multiple interobserver concordance (Fleiss's κ), and percent agreement between recommendations. RESULTS: The mean percent agreement between the total of 1210 observations was 51.3% (95% CI, 48.5-54.1%). Cohen's κ statistic was 0.29 and Fleiss's κ was 0.28. Mean agreement between pairs of human observers only, excluding the MDi-Psoriasis recommendations, was 50.5% (95% CI, 47.6-53.5%). Paired agreement between the recommendations of the MDi-Psoriasis tool and the majority opinion of the expert panel (Cohen's κ) was 0.44 (68.2% agreement). CONCLUSIONS: The MDi-Psoriasis tool can generate recommendations that are comparable to those of experts in psoriasis.

[Nephrotic syndrome in infancy: clinical, therapeutic and follow up characteristics in 100 cases]. / Síndrome nefrótico de la infancia: características clínicas, terapéuticas y evolutivas en 100 casos.

In order to understand the natural history, clinical features, anatomopathological findings and response to the initial treatment with steroids of the nephrotic syndrome (NS) during childhood, a group of 100 children under 14 years (46 with renal biopsy) observed for an average period of 4 years and 8 months, was reviewed retrospectively. The patients were divided into 3 groups: idopathic NC (89), secondary NS (9) and NS in the first six months of life (2). In the group of idiopathic NS, in which the significant predominance of males (2.8/1) was confirmed, in 69% of the patients the diagnosis was made between the ages of 2 and 5 years. Edemas were found, sometimes accompanied by oliguria and weigh gain, in 77% of the cases. The periods of hypertension and hematuria were infrequent and brief. Thirty eight kidney biopsies were carried out and showed: 25 minimal changes NS, 7 diffuse mesangial proliferative glomerulonephritis (DMPGN), 3 membranoproliferative glomerulonephritis (MPGN), 2 membranous glomerulonephritis (MGN) and 1 segmental and focal glomerulosclerosis. Of the 83 patients treated in first instance with corticosteroids, a positive response was obtained in 72 (87%), although 44% of them have shown to be cortico-dependent. After an average follow up period of 4 years and 8 months, only 2 children, one with MPGN and the other with MGN, are now in chronic renal failure (CRF). In 5 ot the 9 patients included in the second group, the NS was secondary to a Henoch Schönlein purpura. The kidney biopsies showed DMPGN in three of them.(ABSTRACT TRUNCATED AT 250 WORDS)

[Metatropic dysplasia: a new case]. / Displasia metatrópica: un nuevo caso.

A new case of metatropic dysplasia in a 2.5 month old child is presented. Diagnoses was made in base of special face, long thorax, shortness of extremities with restricted joint mobility, kyphoscoliosis and a caudal appendage overlying the sacrum. Radiologically, expanded and irregular metaphyses of shortened tubular bones, platyspondyly and kyphoscoliosis. With growth, patients develop changes in body proportions. This syndrome is transmitted as an autosomal recessive. Prevention by genetic counseling is the principal measure.