Towards a strategy for workplace learning: Report to HEFCE by CHERI and KPMG

The study, undertaken between March and November 2005 aimed to inform HEFCE thinking on developing a strategy for workplace learning by: exploring the nature, purposes and outcomes of workplace learning; considering workplace learning within the broader relationships between the worlds of work and learning; exploring emerging changes in higher education which may impact on workplace learning in the future; identifying structural issues that currently enable or inhibit workplace learning, and identify future opportunities

Bostonia. Volume 6

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

La prueba en delitos de tocamientos indebidos en menores de edad distrito, de Comas 2021

La prueba en el delito de tocamientos en menores de edad es cuestionable y no es fácil de acreditar la comisión del delito siendo así que el objetivo general de esta investigación es analizar cómo se garantizaría la eficacia de la prueba en delitos de tocamientos indebidos en menores de edad, distrito de Comas 2021. Asimismo, para el desarrollo de la investigación se empleó el enfoque cualitativo, siendo la investigación básica o pura, con nivel descriptivo y el diseño de teoría fundamentada, del mismo modo se empleó las técnicas de recolección de información fueron la entrevista, aplicado a fiscales provinciales, fiscales adjuntos y jueces y el análisis documental. Finalmente se concluye que las pruebas deben servir a demostrar culpabilidad o inocencia; y en casos no flagrantes una de las pruebas más importantes es la declaración del menor agraviado, siendo así, debe ser recabada bajo los parámetros del Protocolo de Cámara Gesell como prueba anticipada bajo las reglas del Código Procesal Penal de manera oportuna y diligente a fin de que la misma no sea cuestionada en juici

Bostonia. Volume 4

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Optogenetic inhibitor of the transcription factor CREB

Current approaches for optogenetic control of transcription do not mimic the activity of endogenous transcription factors, which act at numerous sites in the genome in a complex interplay with other factors. Optogenetic control of dominant negative versions of endogenous transcription factors provides a mechanism for mimicking the natural regulation of gene expression. Here we describe opto-DN-CREB, a blue light controlled inhibitor of the transcription factor CREB created by fusing the dominant negative inhibitor A-CREB to photoactive yellow protein (PYP). A light driven conformational change in PYP prevents coiled-coil formation between A-CREB and CREB, thereby activating CREB. Optogenetic control of CREB function was characterized in vitro, in HEK293T cells, and in neurons where blue light enabled control of expression of the CREB targets NR4A2 and c-Fos. Dominant negative inhibitors exist for numerous transcription factors; linking these to optogenetic domains offers a general approach for spatiotemporal control of native transcriptional events

Optogenetic inhibitor of the transcription factor CREB

Current approaches for optogenetic control of transcription do not mimic the activity of endogenous transcription factors, which act at numerous sites in the genome in a complex interplay with other factors. Optogenetic control of dominant negative versions of endogenous transcription factors provides a mechanism for mimicking the natural regulation of gene expression. Here we describe opto-DN-CREB, a blue light controlled inhibitor of the transcription factor CREB created by fusing the dominant negative inhibitor A-CREB to photoactive yellow protein (PYP). A light driven conformational change in PYP prevents coiled-coil formation between A-CREB and CREB, thereby activating CREB. Optogenetic control of CREB function was characterized in vitro, in HEK293T cells, and in neurons where blue light enabled control of expression of the CREB targets NR4A2 and c-Fos. Dominant negative inhibitors exist for numerous transcription factors; linking these to optogenetic domains offers a general approach for spatiotemporal control of native transcriptional events

Actualización en el diagnóstico y manejo de la infección urinaria en pediatría

Urinary tract infection is defined as a type of growth of microorganisms in sterilely collected urine from a patient with compatible clinical symptoms, they are one of the most frequent infectious pathologies in the field of pediatrics, occasionally it has been considered as one of the markers of probable anatomical and functional abnormalities of the urinary life, which has become evident and during the last decades those children who present an abnormality of the urinary tract infection underwent imaging studies with the in order to find real scars or anomalies presented in the urinary tract. The objective of this article is to update the clinical management of pediatric patients affected by a urinary tract infection. As a result, it is obtained that, through imaging studies, they make the patient uncomfortable on various occasions, so much so that it is stressful for the parents, the different evidences collected over time and the evidences make it clear that imaging studies must be selective at the moment. to focus on patients. It is concluded that each of the guidelines are based on the urinary tract infection guidelines, trying to verify and demonstrate one of the fundamental and most important pillars to be able to avoid the different renal sequelae in a diagnosis and timely treatment of infections in the urinary tract. febrile urinary tract.La infección urinaria se define como un tipo de crecimiento de microorganismos en orina recogida de forma estéril en un paciente con síntomas clínicos compatibles, son una de las patologías infecciosas más frecuentes en el ámbito de la pediatría, ocasionalmente se ha considerado como uno de los marcadores de probables anomalías anatómicas y funcionales de la vida urinaria, la cual toma constancia u durante las últimas décadas aquellos niños que presentaban una anomalía de la infección en el tracto urinario se sometían a estudios por imágenes con el fin de encontrar cicatrices reales o anormalidades presentadas en la via urinaria. El objetivo del presente artículo es actualizar el manejo clínico de pacientes pediátricos, afectados por una infección en el tracto urinario. Como resultado se obtiene que, mediante los estudios de imágenes en diversas ocasiones incomodan al paciente, tanto así que es estresante para los padres, las distintas evidencias recolectadas con el tiempo y las evidencias dejan claro que, los estudios por imágenes deben ser selectivas al momento de focalizar en los pacientes. Se concluye que, cada una de las pautas están basadas en las guías infección en el tracto urinario intentando comprobar y demostrar uno de los pilares fundamentales y más importantes para poder evitar las distintas secuelas renales en un diagnóstico y un tratamiento oportuno ante las infecciones en el tracto urinario febriles

CTLA4 Message Reflects Pathway Disruption in Monogenic Disorders and Under Therapeutic Blockade

CTLA-4 is essential for immune tolerance. Heterozygous CTLA4 mutations cause immune dysregulation evident in defective regulatory T cells with low levels of CTLA-4 expression. Biallelic mutations in LRBA also result in immune dysregulation with low levels of CTLA-4 and clinical presentation indistinguishable from CTLA-4 haploinsufficiency. CTLA-4 has become an immunotherapy target whereby its blockade with a monoclonal antibody has resulted in improved survival in advanced melanoma patients, amongst other malignancies. However, this therapeutic manipulation can result in autoimmune/inflammatory complications reminiscent of those seen in genetic defects affecting the CTLA-4 pathway. Despite efforts made to understand and establish disease genotype/phenotype correlations in CTLA-4-haploinsufficiency and LRBA-deficiency, such relationships remain elusive. There is currently no specific immunological marker to assess the degree of CTLA-4 pathway disruption or its relationship with clinical manifestations. Here we compare three different patient groups with disturbances in the CTLA-4 pathway—CTLA-4-haploinsufficiency, LRBA-deficiency, and ipilimumab-treated melanoma patients. Assessment of CTLA4 mRNA expression in these patient groups demonstrated an inverse correlation between the CTLA4 message and degree of CTLA-4 pathway disruption. CTLA4 mRNA levels from melanoma patients under therapeutic CTLA-4 blockade (ipilimumab) were increased compared to patients with either CTLA4 or LRBA mutations that were clinically stable with abatacept treatment. In summary, we show that increased CTLA4 mRNA levels correlate with the degree of CTLA-4 pathway disruption, suggesting that CTLA4 mRNA levels may be a quantifiable surrogate for altered CTLA-4 expression

New technologies for examining neuronal ensembles in drug addiction and fear

Correlational data suggest that learned associations are encoded within neuronal ensembles. However, it has been difficult to prove that neuronal ensembles mediate learned behaviours because traditional pharmacological and lesion methods, and even newer cell type-specific methods, affect both activated and non-activated neurons. Additionally, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviourally activated and non-activated neurons. Here, we describe three new approaches—Daun02 inactivation, FACS sorting of activated neurons and c-fos-GFP transgenic rats — that have been used to selectively target and study activated neuronal ensembles in models of conditioned drug effects and relapse. We also describe two new tools — c-fos-tTA mice and inactivation of CREB-overexpressing neurons — that have been used to study the role of neuronal ensembles in conditioned fear

Alternating Hemiplegia of Childhood-Related Neural and Behavioural Phenotypes in Na+,K+-ATPase α3 Missense Mutant Mice

Missense mutations in ATP1A3 encoding Na(+),K(+)-ATPase α3 have been identified as the primary cause of alternating hemiplegia of childhood (AHC), a motor disorder with onset typically before the age of 6 months. Affected children tend to be of short stature and can also have epilepsy, ataxia and learning disability. The Na(+),K(+)-ATPase has a well-known role in maintaining electrochemical gradients across cell membranes, but our understanding of how the mutations cause AHC is limited. Myshkin mutant mice carry an amino acid change (I810N) that affects the same position in Na(+),K(+)-ATPase α3 as I810S found in AHC. Using molecular modelling, we show that the Myshkin and AHC mutations display similarly severe structural impacts on Na(+),K(+)-ATPase α3, including upon the K(+) pore and predicted K(+) binding sites. Behavioural analysis of Myshkin mice revealed phenotypic abnormalities similar to symptoms of AHC, including motor dysfunction and cognitive impairment. 2-DG imaging of Myshkin mice identified compromised thalamocortical functioning that includes a deficit in frontal cortex functioning (hypofrontality), directly mirroring that reported in AHC, along with reduced thalamocortical functional connectivity. Our results thus provide validation for missense mutations in Na(+),K(+)-ATPase α3 as a cause of AHC, and highlight Myshkin mice as a starting point for the exploration of disease mechanisms and novel treatments in AHC