SOCS2 Can Enhance Interleukin-2 (IL-2) and IL-3 Signalling by Accelerating SOCS3 Degradation

Cytokine responses can be regulated by a family of proteins termed suppressors of cytokine signaling (SOCS) which can inhibit the JAK/STAT pathway in a classical negative-feedback manner. While the SOCS are thought to target signaling intermediates for degradation, relatively little is known about how their turnover is regulated. Unlike other SOCS family members, we find that SOCS2 can enhance interleukin-2 (IL-2)- and IL-3-induced STAT phosphorylation following and potentiate proliferation in response to cytokine stimulation. As a clear mechanism for these effects, we demonstrate that expression of SOCS2 results in marked proteasome-dependent reduction of SOCS3 and SOCS1 protein expression. Furthermore, we provide evidence that this degradation is dependent on the presence of an intact SOCS box and that the loss of SOCS3 is enhanced by coexpression of elongin B/C. This suggests that SOCS2 can bind to SOCS3 and elongin B/C to form an E3 ligase complex resulting in the degradation of SOCS3. Therefore, SOCS2 can enhance cytokine responses by accelerating proteasome-dependent turnover of SOCS3, suggesting a mechanism for the gigantism observed in SOCS2 transgenic mice.

Positive and negative contractile effects of somatostatin-14 on rat ventricular cardiomyocytes.

Somatostatin-14 elicits negative inotropic and chronotropic actions in atrial myocardium. Less is known about the effects of somatostatin-14 in ventricular myocardium. The direct contractile effects of somatostatin-14 were assessed using ventricular cardiomyocytes isolated from the hearts of adult rats. Cells were stimulated at 0.5 Hz with CaCl2 (2 mM) under basal conditions and in the presence of the -adrenoceptor agonist, isoprenaline (1 nM), or the selective inhibitor of the transient outward current (Ito), 4-aminopyridine (500 M). Somatostatin-14 did not alter basal contractile response but it did inhibit (IC50 13 nM) the response to isoprenaline (1 nM). In the presence of 4-aminopyridine (500 M), somatostatin-14 stimulated a positive contractile response (EC50 118 fM) that was attenuated markedly by diltiazem (100 nM). These data indicate that somatostatin-14 exerts dual effects directly in rat ventricular cardiomyocytes: (1) a negative contractile effect, observed in the presence of isoprenaline (1 nM), coupled to activation of Ito; and (2) a previously unreported and very potent positive contractile effect, unmasked by 4-aminopyridine (500 M), coupled to the influx of calcium ions via L-type calcium channels. The greater potency of somatostatin-14 for producing the positive contractile effect indicates that the peptide may exert a predominantly stimulatory influence on the resting contractility of ventricular myocardium in vivo, whereas the negative contractile effect, observed at much higher concentrations, could indicate that localized elevations in the concentration of the peptide may serve as a negative regulatory influence to limit the detrimental effects of excessive stimulation of cardiomyocyte contractility.

Factores determinantes del uso de Internet en la comercialización del aceite de oliva. Análisis del sector en Cataluña

Las cooperativas son entidades con una gran presencia económica y social en España, y tienen una gran influencia en la economía rural de las zonas donde están ubicadas. El principal objetivo del presente trabajo es el análisis del uso de las nuevas tecnologías por parte de las cooperativas agroalimentarias, centrándose en las productoras de aceite de oliva para determinar los principales factores que condicionan su comportamiento en la Red. En el presente estudio se analizan sus sitios web y se determina qué tipo de información aporta, tanto datos generales como datos de comercialización. A partir de los resultados obtenidos, se busca la relación que pueda existir entre el tamaño de la cooperativa, su actividad exportadora o la actividad de comercio electrónico con la presencia online, mediante una regresión logística. De esta manera podremos conocer si realmente la implantación de nuevas tecnologías en las cooperativas permite desarrollar una óptima actividad económica.

Interobserver agreement of the Gross Motor Function Classification System in an ambulant population of children with cerebral palsy

Gross Motor Function Classification System (GMFCS) level was reported by three independent assessors in a population of children with cerebral palsy (CP) aged between 4 and 18 years (n=184; 112 males, 72 females; mean age 10y 10mo [SD 3y 7mo]). A software algorithm also provided a computed GMFCS level from a regional CP registry. Participants had clinical diagnoses of unilateral (n=94) and bilateral (n=84) spastic CP, ataxia (n=4), dyskinesia (n=1), and hypotonia (n=1), and could walk independently with or without the use of an aid (GMFCS Levels I-IV). Research physiotherapist (n=184) and parent/guardian data (n=178) were collected in a research environment. Data from the child's community physiotherapist (n=143) were obtained by postal questionnaire. Results, using the kappa statistic with linear weighting (?1w), showed good agreement between the parent/guardian and research physiotherapist (?1w=0.75) with more moderate levels of agreement between the clinical physiotherapist and researcher (?1w=0.64) and the clinical physiotherapist and parent/guardian (?1w=0.57). Agreement was consistently better for older children (>2y). This study has shown that agreement with parent report increases with therapists'experience of the GMFCS and knowledge of the child at the time of grading. Substantial agreement between a computed GMFCS and an experienced therapist (?1w=0.74) also demonstrates the potential for extrapolation of GMFCS rating from an existing CP registry, providing the latter has sufficient data on locomotor ability.

Polynomials on Banach spaces with unconditional bases

We study the classes of homogeneous polynomials on a Banach space with unconditional Schauder basis that have unconditionally convergent monomial expansions relative to this basis. We extend some results of Matos, and we show that the homogeneous polynomials with unconditionally convergent expansions coincide with the polynomials that are regular with respect to the Banach lattices structure of the domain.

Revisión sistemática de la producción española sobre rendimiento académico entre 1980 y 2011

El bajo rendimiento académico sigue siendo un problema de investigación de gran impacto social. Sin embargo, los resultados científicos no están teniendo repercusión en la mejora, ni en las políticas educativas. En este trabajo nos propusimos identificar, ordenar, analizar y extraer conclusiones sobre la producción española sobre rendimiento académico, con el fin de visualizarla y derivar problemas futuros objeto de investigación. Para ello se llevó a cabo un estudio de revisión en seis etapas, en el que se combinaron procedimientos metodológicos de investigación de síntesis y de investigación bibliométrica. Se identificaron las publicaciones en cuatro bases de datos españolas; posteriormente se analizaron y codificaron los datos extraídos alrededor de nueve indicadores: título, año, tipo de documento, editorial, autor, número autores, institución, comunidad autónoma y tema. Los resultados muestran una producción constante y creciente (1595 referencias), pero dispersa, tanto por el inmenso número de autores que publican, la mayoría con un solo trabajo, como por los lugares donde publican. Las temáticas más tratadas se refieren en primer lugar a modelos explicativos, diagnóstico y tratamiento; en segundo lugar se abordan los factores y variables determinantes del bajo y alto rendimiento académico; en tercer lugar se desarrollan estudios sobre legislación y de otras variables psicológicas y educativas en relación con el rendimiento. Este estudio supone una aproximación sintetizada de la producción sobre rendimiento académico en España, y un primer paso para investigaciones de síntesis posteriores, que nos permitan identificar buenas prácticas para el ejercicio de “prácticas basadas en la evidencia”, y otros problemas de investigación.

Energy efficiency in gait, activity, participation, and health status in children with cerebral palsy

The aim of the study was to establish if a relationship exists between the energy efficiency of gait, and measures of activity limitation, participation restriction, and health status in a representative sample of children with cerebral palsy (CP). Secondary aims were to investigate potential differences between clinical subtypes and gross motor classification, and to explore other relationships between the measures under investigation. A longitudinal study of a representative sample of 184 children with ambulant CP was conducted (112 males, 72 females; 94 had unilateral spastic C P, 84 had bilateral spastic C P, and six had non-spastic forms; age range 4-17y; Gross Motor Function Classification System Level I, n=57; Level II, n=91; Level III, n=22; and Level IV, n=14); energy efficiency (oxygen cost) during gait, activity limitation, participation restriction, and health status were recorded. Energy efficiency during gait was shown to correlate significantly with activity limitations; no relationship between energy efficiency during gait was found with either participation restriction or health status. With the exception of psychosocial health, all other measures showed significant differences by clinical subtype and gross motor classification. The energy efficiency of walking is not reflective of participation restriction or health status. Thus, therapies leading to improved energy efficiency may not necessarily lead to improved participation or general health.

Physicochemical characterization of bioactive polyacrylic acid organogels as potential antimicrobial implants for the buccal cavity

This study describes the formulation and physicochemical characterization of poly(acrylic acid) (PAA) organogels, designed as bioactive implants for improved treatment of infectious diseases of the oral cavity. Organogels were formulated containing a range of concentrations of PAA (3-10% w/w) and metronidazole (2 or 5% w/w, representing a model antimicrobial agent) in different nonaqueous solvents, namely, glycerol (Gly), polyethylene glycol (PEG 400), or propylene glycol (PG). Characterization of the organogels was performed using flow rheometry, compressional analysis, oscillatory rheometry, in vitro mucoadhesion, moisture uptake, and drug release, methods that provide information pertaining to the nonclinical and clinical use of these systems. Increasing the concentration of PAA significantly increased the consistency, compressibility, storage modulus, loss modulus, dynamic viscosity, mucoadhesion, and the rate of drug release. These observations may be accredited to enhanced molecular polymer entanglement. In addition, the choice of solvent directly affected the physicochemical parameters of the organogels, with noticeable differences observed between the three solvents examined. These differences were accredited to the nature of the interaction of PAA with each solvent and, importantly, the density of the resultant physical cross-links. Good correlation was observed between the viscoelastic properties and drug release, with the exception of glycerol-based formulations containing 5 and 10% w/w PAA. This disparity was due to excessive swelling during the dissolution analysis. Ideally, formulations should exhibit controlled drug release, high viscoelasticity, and mucoadhesion, but should flow under minimal stresses. Based on these criteria, PEG 400-based organogels composed of 5% or 10% w/w PAA exhibited suitable physicochemical properties and are suggested to be a potentially interesting strategy for use as bioactive implants designed for use in the oral cavity. © 2008 American Chemical Society.