Identification of lactic acid bacteria strains modulating incretin hormone secretion and gene expression in enteroendocrine cells

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones released from intestinal enteroendocrine (EE) cells and have well-established glucose-lowering actions. Lactic acid bacteria (LAB) colonise the human intestine, but it is unknown whether LAB and EE cells interact. Acute co-culture of LAB with EE cells showed that certain LAB strains elicit GLP-1 and GIP secretion (13-194-fold) and upregulate their gene expression. LAB-induced incretin hormone secretion did not appear to involve nutrient mechanisms, nor was there any evidence of cytolysis. Instead PCR array studies implicated signalling agents of the toll-like receptor system, e.g. adaptor protein MyD88 was decreased 23-fold and cell surface antigen CD14 was increased 17-fold. Mechanistic studies found that blockade of MyD88 triggered significant GLP-1 secretion. Furthermore, blocking of CD14 completely attenuated LAB-induced secretion. A recent clinical trial clearly shows that LAB have potential for alleviating type 2 diabetes, and further characterisation of this bioactivity is warranted.

Evolving techniques for monitoring geotechnical risk on the Antrim Coast Road.

The interaction between problematic geology and environmental variables along the Antrim Coast Road results in frequent instances of geotechnical instability. During such instances of instability, mudslide debris encroaches on the carriageway posing a hazard to motorists, causing lengthily tailbacks. This paper examines some of the geotechnical and spatial analysis techniques currently being implemented to monitor slope stability on this key transport route.

Geotechnical monitoring using a combination of LIDAR, real-time dGPS, and electrical tomography to assess geotechnical risk of a coastal landslide.

The Antrim Coast Road stretching from the seaport of Larne in the East of Northern Ireland has a well-deserved reputation for being one of the most spectacular roads in Europe (Day, 2006). However the problematic geology; Jurassic Lias Clay and Triassic Mudstone overlain by Cretaceous Limestone and Tertiary Basalt, and environmental variables result in frequent instances of slope instability manifested in both shallow debris flows and occasional massive rotational movements, creating a geotechnical risk to this highway. This paper describes how a variety of techniques are being used to both assess instability and monitor movement of these active slopes near one site at Straidkilly Point, Glenarm. An in-depth understanding of the geology was obtained via boreholes, resistivity surveys and laboratory testing. Environmental variables recorded by an on-site weather station were correlated with measured pore water pressure and soil moisture infiltration data. Terrestrial LiDAR (TLS), with surveys carried out on a bi-monthly basis allowed for the generation of Digital Elevation Models (DEMs) of difference, highlighting areas of recent movement, accumulation and depletion. Morphology parameters were generated from the DEMs and include slope, curvature and multiple measures of roughness. Changes in the structure of the slope coupled with morphological parameters were characterised and linked to progressive failures from the temporal monitoring. In addition to TLS monitoring, Aerial LiDAR datasets were used for the spatio-morphological characterisation of the slope on a macro scale. A Differential Global Positioning System (dGPS) was also deployed on site to provide a real-time warning system for gross movements, which were also correlated with environmental conditions. Frequent electrical resistivity tomography (ERT) surveys were also implemented to provide a better understanding of long-term changes in soil moisture and help to define the complex geology. The paper describes how the data obtained via a diverse range of methods has been combined to facilitate a more informed management regime of geotechnical risk by the Northern Ireland Roads Service.

Papel de la autoevaluación en la formación integral de los estudiantes Un estudio de caso con estudiantes de Fisioterapia de la Universidad Nacional de Colombia

En su sentido más sencillo, la evaluación conduce a una opinión fundada en que algo es de un cierto modo. No tiene porque llevar a una decisión respecto a una determinada forma de actuar, aunque hoy día a menudo, pretende tal cosa.

Tendencias en evaluación.

La evaluación se desarrolla como una estrategia para encontrar grandes soluciones a los problemas sociales. La evaluación se considera una actividad con efectos e implicaciones políticas. Se desarrollan los cambios estructurales y conceptuales de la evaluación, que son estimulados por la r��pida evolución del contexto social, en relación con el cambio del car��cter en la sociedad norteamericana.

Tres perspectivas de la innovación educativa : tecnología, política y cultura.

Estos tres marcos son bastante básicos, pues sus perspectivas encierran formas fundamentales de enfocar no sólo dicha innovación educativa, sino la propia sociedad, estas tres perspectivas reflejan en esencia las acciones de instituciones concretas de la sociedad. Se corresponden con: la infraestructura, la estructura y la superestructura de la sociedad, es decir, las formas básicas de producción y reproducción constituyen la infraestructura de la sociedad, la economía doméstica y la política son la estructura, y actividades como las artes, la ciencia, los ritos y los deportes forman la superestructura. En Estados Unidos existen en la actualidad dos corrientes principales para la reforma educativa: 1õ. El movimiento de alfabetización cultural que se basa en la explicación de que el declive de este país es cultural y no tecnológico, ni político. La propia cultura se considera la fuerza motriz, a pesar de que el declive cultural tenga ramificaciones políticas y económicas y esté motivado, en parte por una influencia política inadecuada. Esta explicación neoconservadora culpa a las instituciones educativas, más que a las económicas o políticas; 2õ Este movimiento se basa en la imposición de evaluaciones dependientes de cada estado y de programas de rendición de cuentas, siendo los cincuenta estados las unidades de gobierno que regulan directamente las escuelas. La mayor parte de los estados han promulgado leyes que prescriben pruebas normalizadas para medir el rendimiento, de forma que se hace responsables a las escuelas y al profesorado de que se eleven las puntuaciones en las pruebas de un año a otro. El fundamento de este enfoque es la conocida perspectiva tecnológica, tomada directamente de la producción industrial. Al asignar un indicador cuantitativo, como son las notas, a la escuela, las autoridades superiores pueden controlar el rendimiento de profesores y alumnos como en una fábrica. Se presupone que ello, obligar�� a estos últimos a trabajar más y elevar el nivel educativo, pero lo que a menudo sucede es que los profesores enseñen a resolver las propias pruebas ¿Cuál de las tres perspectivas ofrece una explicación más convincente? Las tres son necesarias para explicar íntegramente los acontecimientos sociales, porque llega un momento en que intervienen todas las instituciones sociales. Pero, no todas estas explicaciones tienen la misma importancia, ya que a pesar de que los acontecimientos sociales dependen de todas las instituciones, algunas son más responsables que otras de lo que ocurre. En última instancia la respuesta se obtendr�� recopilando información sobre las tendencias educativas y sociales a largo plazo.

Clustered functional MRI of overt speech production

To investigate the neural network of overt speech production, eventrelated fMRI was performed in 9 young healthy adult volunteers. A clustered image acquisition technique was chosen to minimize speechrelated movement artifacts. Functional images were acquired during the production of oral movements and of speech of increasing complexity (isolated vowel as well as monosyllabic and trisyllabic utterances). This imaging technique and behavioral task enabled depiction of the articulo-phonologic network of speech production from the supplementary motor area at the cranial end to the red nucleus at the caudal end. Speaking a single vowel and performing simple oral movements involved very similar activation of the corticaland subcortical motor systems. More complex, polysyllabic utterances were associated with additional activation in the bilateral cerebellum,reflecting increased demand on speech motor control, and additional activation in the bilateral temporal cortex, reflecting the stronger involvement of phonologic processing.

The effects of strategy instruction on writing strategy use for students of different proficiency levels

Learners’ strategy use has been widely researched over the past few decades. However, studies which focus on the impact of strategy instruction on strategy use, and how far learners of different proficiency levels are able to use the strategies taught in an effective manner, are somewhat rare. The focus of this paper is the impact of writing strategy instruction on writing strategy use of a group of 12 second language learners learning to write in English for Academic Purposes classes. Stimulated recall was used to explore whether this impact differed according to the proficiency level of the students, and revealed that for both high and low proficiency learners’ strategy use developed as a result of the instruction. The implications of these findings for strategy instruction design are discussed

Production of bioactive diterpenoids in the Euphorbiaceae depends on evolutionarily conserved gene clusters

The Euphorbiaceae produce a diverse range of diterpenoids, many of which have pharmacological activities. These diterpenoids include ingenol mebutate, which is licensed for the treatment of a precancerous skin condition (actinic keratosis), and phorbol derivatives such as resiniferatoxin and prostratin, which are undergoing investigation for the treatment of severe pain and HIV, respectively. Despite the interest in these diterpenoids, their biosynthesis is poorly understood at present, with the only characterized step being the conversion of geranylgeranyl pyrophosphate into casbene. Here, we report a physical cluster of diterpenoid biosynthetic genes from castor (Ricinus communis), including casbene synthases and cytochrome P450s from the CYP726A subfamily. CYP726A14, CYP726A17, and CYP726A18 were able to catalyze 5-oxidation of casbene, a conserved oxidation step in the biosynthesis of this family of medicinally important diterpenoids. CYP726A16 catalyzed 7,8-epoxidation of 5-keto-casbene and CYP726A15 catalyzed 5-oxidation of neocembrene. Evidence of similar gene clustering was also found in two other Euphorbiaceae, including Euphorbia peplus, the source organism of ingenol mebutate. These results demonstrate conservation of gene clusters at the higher taxonomic level of the plant family and that this phenomenon could prove useful in further elucidating diterpenoid biosynthetic pathways.

The opioid antagonist naltrexone and its pharmacological role in treating alcohol dependence: A literature review

Naltrexone, an opioid antagonist, was the second drug approved for treatment of alcohol dependence in the U.S. Its approval followed two landmark studies published in the U.S. in 1992. [1, 2] These studies showed that a combined treatment of naltrexone and behavioral therapy reduced alcohol consumption in alcoholics. Opioid antagonists decrease craving for alcohol and help to reduce drinking by blocking opioid peptide receptors in the body that are active in a dopamine chemical reward system. ^ Despite their usefulness, opioid antagonists have been underutilized. Health providers not educated in the use of opioid antagonists hold the view that opioid antagonist therapy is ineffective. However, it is apparent from the relevant literature that this therapy, when properly understood and targeted, has the potential to make a positive contribution in treating alcohol dependent patients. ^ This thesis will review the scientific literature and the present body of knowledge regarding opioid antagonists (naltrexone) and their pharmacological role in treating alcohol dependence.^

Domain-specific gene disruption reveals critical regulation of neuregulin signaling by its cytoplasmic tail

Neuregulins are a multi-isoform family of growth factors that activate members of the erbB family of receptor tyrosine kinases. The membrane-anchored isoforms contain the receptor-activating ligand in their extracellular domain, a single membrane-spanning region, and a long cytoplasmic tail. To evaluate the potential biological role of the intracellular domain of the membrane-anchored neuregulin isoforms, we used a domain-specific gene disruption approach to produce a mouse line in which only the region of the neuregulin gene encoding almost the entire intracellular domain was disrupted. Consistent with previous reports in which all neuregulin isoforms were disrupted, the resulting homozygous neuregulin mutants died at E10.5 of circulatory failure and displayed defects in neural and cardiac development. To further understand these in vivo observations, we evaluated a similarly truncated neuregulin construct after transient expression in COS-7 cells. This cytoplasmic tail-deleted mutant, unlike wild-type neuregulin isoforms, was resistant to proteolytic release of its extracellular-domain ligand, a process required for erbB receptor activation. Thus, proteolytic processing of the membrane-bound neuregulin isoforms involved in cranial ganglia and heart embryogenesis is likely developmentally regulated and is critically controlled by their intracellular domain. This observation indicates that erbB receptor activation by membrane-bound neuregulins most likely involves a unique temporally and spatially regulated “inside-out” signaling process that is critical for processing and release of the extracellular-domain ligand.