17O NMR and FT-IR study of the ionization state of peptides in aprotic solvents Application to Leu-enkephalin

AbstractThe ionization state of Leu-enkephalin in DMSO and MeCN/DMSO (4/1) solution was studied by the combined use of 17O NMR and FT-IR spectroscopy. After lyophilization or an aqueous solution at nearly neutral pH, Leu-enkephalin essentially exists in the uncharged state in MeCN/DMSO (4/1) solution. In pure DMSO, only 40% of the Leu-enkephalin molecules are in the zwitterionic state under the same conditions

Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons

Neurogliaform (RELN+) and bipolar (VIP+) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been elucidated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). Interestingly, Prox1 promotes the maturation of CGE-derived interneuron subtypes through intrinsic differentiation programs that operate in tandem with extrinsically driven neuronal activity-dependent pathways. Thus Prox1 represents the first identified transcription factor specifically required for the embryonic and postnatal acquisition of CGE-derived cortical interneuron properties. SIGNIFICANCE STATEMENT: Despite the recognition that 30% of GABAergic cortical interneurons originate from the caudal ganglionic eminence (CGE), to date, a specific transcriptional program that selectively regulates the development of these populations has not yet been identified. Moreover, while CGE-derived interneurons display unique patterns of tangential and radial migration and preferentially populate the superficial layers of the cortex, identification of a molecular program that controls these events is lacking.Here, we demonstrate that the homeodomain transcription factor Prox1 is expressed in postmitotic CGE-derived cortical interneuron precursors and is maintained into adulthood. We found that Prox1 function is differentially required during both embryonic and postnatal stages of development to direct the migration, differentiation, circuit integration, and maintenance programs within distinct subtypes of CGE-derived interneurons

Can group-based reassuring information alter low back pain behavior? A cluster-randomized controlled trial?

Background Low back pain (LBP) is common in the population and multifactorial in nature, often involving negative consequences. Reassuring information to improve coping is recommended for reducing the negative consequences of LBP. Adding a simple non-threatening explanation for the pain (temporary muscular dysfunction) has been successful at altering beliefs and behavior when delivered with other intervention elements. This study investigates the isolated effect of this specific information on future occupational behavior outcomes when delivered to the workforce. Design A cluster-randomized controlled trial. Methods Publically employed workers (n=505) from 11 Danish municipality centers were randomized at center-level (cluster) to either intervention (two 1-hour group-based talks at the workplace) or control. The talks provided reassuring information together with a simple non-threatening explanation for LBP - the ‘functional-disturbance’-model. Data collections took place monthly over a 1-year period using text message tracking (SMS). Primary outcomes were self-reported days of cutting down usual activities and work participation. Secondary outcomes were self-reported back beliefs, work ability, number of healthcare visits, bothersomeness, restricted activity, use of pain medication, and sadness/depression. Results There was no between-group difference in the development of LBP during follow-up. Cumulative logistic regression analyses showed no between-group difference on days of cutting down activities, but increased odds for more days of work participation in the intervention group (OR=1.83 95% CI: 1.08-3.12). Furthermore, the intervention group was more likely to report: higher work ability, reduced visits to healthcare professionals, lower bothersomeness, lower levels of sadness/depression, and positive back beliefs. Conclusion Reassuring information involving a simple non-threatening explanation for LBP significantly increased the odds for days of work participation and higher work ability among workers who went on to experience LBP during the 12-month follow-up. Our results confirm the potential for public-health education for LBP, and add to the discussion of simple versus multidisciplinary interventions

Isotopic Grand Unification with the Inclusion of Gravity (revised version)

We introduce a dual lifting of unified gauge theories, the first characterized by the isotopies, which are axiom- preserving maps into broader structures with positive-definite generalized units used for the representation of matter under the isotopies of the Poincare' symmetry, and the second characterized by the isodualities, which are anti-isomorphic maps with negative-definite generalized units used for the representation of antimatter under the isodualities of the Poincare' symmetry. We then submit, apparently for the first time, a novel grand unification with the inclusion of gravity for matter embedded in the generalized positive-definite units of unified gauge theories while gravity for antimatter is embedded in the isodual isounit. We then show that the proposed grand unification provides realistic possibilities for a resolution of the axiomatic incompatibilities between gravitation and electroweak interactions due to curvature, antimatter and the fundamental space-time symmetries.Comment: 20 pages, Latex, revised in various details and with added reference

A concept design and decision making model for alternative high-speed ferries

Available from British Library Document Supply Centre-DSC:DXN031125 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

GABAergic and pyramidal neurons of deep cortical layers directly receive and differently integrate callosal input.

We studied the involvement of deep cortical layer neurons in processing callosal information in the rat. We observed with electron microscopy that both parvalbumin (PV)-labeled profiles and unlabeled dendritic spines of deep cortical layer neurons receive synapses from the contralateral hemisphere. Stimulation of callosal fibers elicited monosynaptic excitatory postsynaptic currents in both layer VI pyramidal neurons and gamma-aminobutyric acidergic (GABAergic) interneurons immunopositive for the vesicular GABA transporter and PV. Pyramidal cells had intrinsic electrophysiological properties and synaptic responses with slow kinetics and a robust N-metyhl-D-aspartate (NMDA) component. In contrast, GABAergic interneurons had intrinsic membrane properties and synaptic responses with faster kinetics and a less pronounced NMDA component. Consistent with these results, the temporal integration of callosal input was effective over a significantly longer time window in pyramidal neurons compared with GABAergic interneurons. Interestingly, callosal stimulation did not evoke feedforward inhibition in all GABAergic interneurons and in the majority of pyramidal neurons tested. Furthermore, retrogradely labeled layer VI pyramidal neurons of the contralateral cortex responded monosynaptically to callosal stimulation, suggesting interconnectivity between callosally projecting neurons. The data show that pyramidal neurons and GABAergic interneurons of deep cortical layers receive interhemispheric information directly and have properties supporting their distinct roles