Информационные технологии в управлении интеллектуальным капиталом организации

The report examines how organization can use information technologies for management of intellectual capital

Upregulation of Immunoproteasome Subunits in Myositis Indicates Active Inflammation with Involvement of Antigen Presenting Cells, CD8 T-Cells and IFN gamma

Objective: In idiopathic inflammatory myopathies (IIM) infiltration of immune cells into muscle and upregulation of MHC-I expression implies increased antigen presentation and involvement of the proteasome system. To decipher the role of immunoproteasomes in myositis, we investigated individual cell types and muscle tissues and focused on possible immune triggers. Methods: Expression of constitutive (PSMB5,-6,-7) and corresponding immunoproteasomal subunits (PSMB8,-9,-10) was analyzed by real-time RT-PCR in muscle biopsies and sorted peripheral blood cells of patients with IIM, non-inflammatory myopathies (NIM) and healthy donors (HD). Protein analysis in muscle biopsies was performed by western blot. Affymetrix HG-U133 platform derived transcriptome data from biopsies of different muscle diseases and from immune cell types as well as monocyte stimulation experiments were used for validation, coregulation and coexpression analyses. Results: Real-time RT-PCR revealed significantly increased expression of immunoproteasomal subunits (PSMB8/-9/-10) in DC, monocytes and CD8+ T-cells in IIM. In muscle biopsies, the immunosubunits were elevated in IIM compared to NIM and exceeded levels of matched blood samples. Proteins of PSMB8 and -9 were found only in IIM but not NIM muscle biopsies. Reanalysis of 78 myositis and 20 healthy muscle transcriptomes confirmed these results and revealed involvement of the antigen processing and presentation pathway. Comparison with reference profiles of sorted immune cells and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. This upregulation correlated highest with STAT1, IRF1 and IFN gamma expression. Elevation of T-cell specific transcripts in active IIM muscles was accompanied by increased expression of DC and monocyte marker genes and thus reflects the cell type specific involvement observed in peripheral blood. Conclusions: Immunoproteasomes seem to indicate IIM activity and suggest that dominant involvement of antigen processing and presentation may qualify these diseases exemplarily for the evolving therapeutic concepts of immunoproteasome specific inhibition

Upregulation of Immunoproteasome Subunits in Myositis Indicates Active Inflammation with Involvement of Antigen Presenting Cells, CD8 T-Cells and IFN gamma

Objective: In idiopathic inflammatory myopathies (IIM) infiltration of immune cells into muscle and upregulation of MHC-I expression implies increased antigen presentation and involvement of the proteasome system. To decipher the role of immunoproteasomes in myositis, we investigated individual cell types and muscle tissues and focused on possible immune triggers. Methods: Expression of constitutive (PSMB5,-6,-7) and corresponding immunoproteasomal subunits (PSMB8,-9,-10) was analyzed by real-time RT-PCR in muscle biopsies and sorted peripheral blood cells of patients with IIM, non-inflammatory myopathies (NIM) and healthy donors (HD). Protein analysis in muscle biopsies was performed by western blot. Affymetrix HG-U133 platform derived transcriptome data from biopsies of different muscle diseases and from immune cell types as well as monocyte stimulation experiments were used for validation, coregulation and coexpression analyses. Results: Real-time RT-PCR revealed significantly increased expression of immunoproteasomal subunits (PSMB8/-9/-10) in DC, monocytes and CD8+ T-cells in IIM. In muscle biopsies, the immunosubunits were elevated in IIM compared to NIM and exceeded levels of matched blood samples. Proteins of PSMB8 and -9 were found only in IIM but not NIM muscle biopsies. Reanalysis of 78 myositis and 20 healthy muscle transcriptomes confirmed these results and revealed involvement of the antigen processing and presentation pathway. Comparison with reference profiles of sorted immune cells and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. This upregulation correlated highest with STAT1, IRF1 and IFN gamma expression. Elevation of T-cell specific transcripts in active IIM muscles was accompanied by increased expression of DC and monocyte marker genes and thus reflects the cell type specific involvement observed in peripheral blood. Conclusions: Immunoproteasomes seem to indicate IIM activity and suggest that dominant involvement of antigen processing and presentation may qualify these diseases exemplarily for the evolving therapeutic concepts of immunoproteasome specific inhibition

SIL1 mutations and clinical spectrum in patients with Marinesco-Sjögren syndrome

Marinesco-Sjögren syndrome is a rare autosomal recessive multisystem disorder featuring cerebellar ataxia, early-onset cataracts, chronic myopathy, variable intellectual disability and delayed motor development. More recently, mutations in the SIL1 gene, which encodes an endoplasmic reticulum resident co-chaperone, were identified as the main cause of Marinesco-Sjögren syndrome. Here we describe the results of SIL1 mutation analysis in 62 patients presenting with early-onset ataxia, cataracts and myopathy or combinations of at least two of these. We obtained a mutation detection rate of 60% (15/25) among patients with the characteristic Marinesco-Sjögren syndrome triad (ataxia, cataracts, myopathy) whereas the detection rate in the group of patients with more variable phenotypic presentation was below 3% (1/37). We report 16 unrelated families with a total of 19 different SIL1 mutations. Among these mutations are 15 previously unreported changes, including single- and multi-exon deletions. Based on data from our screening cohort and data compiled from the literature we found that SIL1 mutations are invariably associated with the combination of a cerebellar syndrome and chronic myopathy. Cataracts were observed in all patients beyond the age of 7 years, but might be missing in infants. Six patients with SIL1 mutations had no intellectual disability, extending the known wide range of cognitive capabilities in Marinesco-Sjögren syndrome to include normal intelligence. Modestly constant features were somatic growth retardation, skeletal abnormalities and pyramidal tract signs. Examination of mutant SIL1 expression in cultured patient lymphoblasts suggested that SIL1 mutations result in severely reduced SIL1 protein levels irrespective of the type and position of mutations. Our data broaden the SIL1 mutation spectrum and confirm that SIL1 is the major Marinesco-Sjögren syndrome gene. SIL1 patients usually present with the characteristic triad but cataracts might be missing in young children. As cognitive impairment is not obligatory, patients without intellectual disability but a Marinesco-Sjögren syndrome-compatible phenotype should receive SIL1 mutation analysis. Despite allelic heterogeneity and many families with private mutations, the phenotype related to SIL1 mutations is relatively homogenous. Based on SIL1 expression studies we speculate that this may arise from a uniform effect of different mutations on protein expressio

Efectos del entrenamiento de la musculatura respiratoria sobre el rendimiento.

Actualmente, es aceptado por la comunidad científica que el sistema respiratorio puede limitar el ejercicio en personas con enfermedad pulmonar y/o cardiovascular. El objetivo del presente artículo es la revisión de algunos estudios realizados en relación al papel limitante del sistema respiratorio en el rendimiento físico de deportistas. Se realiza una breve descripción técnica de los dispositivos más utilizados para el entrenamiento de la musculatura respiratoria. Finalmente, se presentan los resultados más representativos, obtenidos por diversos investigadores y en distintas poblaciones, relacionados con el entrenamiento de la musculatura respiratoria y sus efectos en el rendimiento físico. Los resultados obtenidos en las distintas investigaciones consultadas sobre el entrenamiento de los músculos respiratorios son dispares, puesto que algunos han mostrado mejoras significativas, mientras otros no han mostrado grandes efectos en el rendimiento. En todos ellos se refleja cómo el sistema respiratorio es un factor limitante del rendimiento físico en deportistas y es preciso plantearse nuevas metodologías, protocolos y planificaciones en el entrenamiento deportivo. El entrenamiento de los músculos respiratorios, tanto mediante dispositivos umbral, de resistencia, o isocapnica, puede provocar mejoras en valores como la presión inspiratoria máxima y mejoras en el rendimiento de algunos deportes; sin embargo, son muy escasos los estudios que han encontrado mejoras en el consumo máximo de oxígeno (VO2max). Las discrepancias entre los estudios analizados pueden estar provocadas por diferencias en las intensidades y duración de los ejercicios utilizados, así como por diferencias en el diseño experimental y el nivel de condición física de los sujetos

Single and repeated moderate consumption of native or dealcoholized red wine show different effects on antioxidant parameters in blood and DNA strand breaks in peripheral leukocytes in healthy volunteers: a randomized controlled trial [ISRCTN68505294]

BACKGROUND: Red wine (RW) is rich in antioxidant polyphenols that might protect from oxidative stress related diseases, such as cardiovascular disease and cancer. Antioxidant effects after single ingestion of RW or dealcoholized RW (DRW) have been observed in several studies, but results after regular consumption are contradictory. Thus, we examined if single or repeated consumption of moderate amounts of RW or DRW exert antioxidant activity in vivo. METHODS: Total phenolic content and concentration of other antioxidants in plasma/serum, total antioxidant capacity (TEAC) in plasma as well as DNA strand breaks in peripheral leukocytes were measured in healthy non-smokers A) before, 90 and 360 min after ingestion of one glass of RW, DRW or water; B) before and after consumption of one glass of RW or DRW daily for 6 weeks. DNA strand breaks (SB) were determined by single cell gel electrophoresis (Comet Assay) in untreated cells and after induction of oxidative stress ex vivo with H(2)O(2 )(300 μM, 20 min). RESULTS: Both RW and DRW transiently increased total phenolic content in plasma after single consumption, but only RW lead to a sustained increase if consumed regularly. Plasma antioxidant capacity was not affected by single or regular consumption of RW or DRW. Effects of RW and DRW on DNA SB were conflicting. DNA strand breaks in untreated cells increased after a single dose of RW and DRW, whereas H(2)O(2 )induced SB were reduced after DRW. In contrast, regular RW consumption reduced SB in untreated cells but did not affect H(2)O(2 )induced SB. CONCLUSION: The results suggest that consumption of both RW and DRW leads to an accumulation of phenolic compounds in plasma without increasing plasma antioxidant capacity. Red wine and DRW seem to affect the occurrence of DNA strand breaks, but this cannot be referred to antioxidant effects

Man and the Last Great Wilderness: Human Impact on the Deep Sea

The deep sea, the largest ecosystem on Earth and one of the least studied, harbours high biodiversity and provides a wealth of resources. Although humans have used the oceans for millennia, technological developments now allow exploitation of fisheries resources, hydrocarbons and minerals below 2000 m depth. The remoteness of the deep seafloor has promoted the disposal of residues and litter. Ocean acidification and climate change now bring a new dimension of global effects. Thus the challenges facing the deep sea are large and accelerating, providing a new imperative for the science community, industry and national and international organizations to work together to develop successful exploitation management and conservation of the deep-sea ecosystem. This paper provides scientific expert judgement and a semi-quantitative analysis of past, present and future impacts of human-related activities on global deep-sea habitats within three categories: disposal, exploitation and climate change. The analysis is the result of a Census of Marine Life – SYNDEEP workshop (September 2008). A detailed review of known impacts and their effects is provided. The analysis shows how, in recent decades, the most significant anthropogenic activities that affect the deep sea have evolved from mainly disposal (past) to exploitation (present). We predict that from now and into the future, increases in atmospheric CO2 and facets and consequences of climate change will have the most impact on deep-sea habitats and their fauna. Synergies between different anthropogenic pressures and associated effects are discussed, indicating that most synergies are related to increased atmospheric CO2 and climate change effects. We identify deep-sea ecosystems we believe are at higher risk from human impacts in the near future: benthic communities on sedimentary upper slopes, cold-water corals, canyon benthic communities and seamount pelagic and benthic communities. We finalise this review with a short discussion on protection and management methods

Maximal cardiac output during arm exercise in the sitting position after cervical spinal cord injury

OBJECTIVE: To determine and compare haemodynamic responses at maximal arm-crank (ACE) and wheelchair exercise (WCE) in individuals with cervical spinal cord injury and pair-matched able-bodied individuals. METHODS: Nine male, motor-complete cervical spinal cord injured and 9 able-bodied individuals performed graded, maximal ACE and WCE. Cardiac output, heart rate, and stroke volume were determined at rest and at maximal exercise in cervical spinal cord injured individuals. In able-bodied individuals, measurements were performed at rest and at the maximal workload of the matched cervical spinal cord injured individuals. RESULTS: In cervical spinal cord injured, maximal cardiac output (ACE 7.4 (standard deviation (SD) 1.6); WCE 7.3 (SD 2.1) l/min) and heart rate (ACE 101 (SD 22); WCE 103 (SD 27) bpm) increased significantly compared with rest (4.6 (SD 1.0) l/min; 65 (SD 12) bpm), while stroke volume (ACE 77 (SD 22); WCE 73 (SD 21) ml) did not differ from rest (73 (SD 20) ml). In able-bodied individuals, cardiac output (rest 4.8 (SD 1.4); ACE 10.7 (SD 1.8); WCE 10.3 (SD 2.2) l/min), heart rate (rest 68 (SD 10); ACE 103 (SD 27); WCE 109 (SD 27) bpm), and stroke volume (rest 70 (SD 10); ACE 105 (SD 20); WCE 96 (SD 17) ml) increased significantly compared with rest. Cardiac output and stroke volume were significantly lower in cervical spinal cord injured compared with able-bodied individuals at the same workloads. CONCLUSION: Haemodynamic responses to maximal exercise were similar for both exercise modes in individuals with cervical spinal cord injury. The lower cardiac output in individuals with cervical spinal cord injury compared with able-bodied individuals at equivalent workloads reflects the inability of the circulatory system to increase stroke volume