Current Perspective on the Location and Function of Gamma- Aminobutyric Acid (GABA) and its Metabolic Partners in the Kidney.

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter located in the mammalian central nervous system, which binds to GABAA and GABAB receptors to mediate its neurological effects. In addition to its role in the CNS, an increasing number of publications have suggested that GABA might also play a role in the regulation of renal function. All three enzymes associated with GABA metabolism; glutamic acid decarboxylase, GABA ?-oxoglutarate transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH) have been localised to the kidney providing the necessary machinery for localised GABA synthesis and metabolism. Moreover GABA receptors have been localised to both tubular and vascular structures in the kidney, and GABA is excreted in urine (~3 ?M) in humans. Despite the collective evidence describing the presence of a GABA system in the kidney, the precise function of such a system requires further clarification. Here we provide an overview of the current renal GABA literature and provide novel data that indicates GABA can act at contractile pericyte cells located along vasa recta capillaries in the renal medulla to potentially regulate medullary blood flow

Observation of ultrafast internal conversion in fullerene anions in solution

The ultrafast decay rates of photoexcited View the MathML source ions have been measured in the condensed phase. The mechanism for decay is internal conversion, and the decay rate is a strong function of the charge on the ion. A bottleneck in the ground state recovery has also been detected, and its interpretation is discussed

Who Needs Good Neighbours?

Abstract: Due to the increasing spatial dispersion of social networks, the association between neighbor relationships and quality of life has become more uncertain. Our analysis used instrumental variable modelling to reduce bias associated with residual confounding and reverse causation, in order to provide a more reliable examination of the effect of interaction with neighbors on subjective well-being than previous work. While the frames of reference for individuals’ socializing may have shifted outside the neighborhood, our analysis provides robust evidence that interaction with neighbors still matters a great deal for subjective well-being. A further important question to ask is if neighboring does affect well-being, then are there certain groups in society for whom contact with neighbors matters more? Our analysis suggests that there are, namely for those in a relationship, unemployed or retired. This means that while fostering contact with neighbors has the potential to significantly improve individual well-being, such policy efforts are likely to matter a good deal more in neighborhoods with relatively large numbers of geographically constrained social groups, such as the elderly and the unemployed. Key words: subjective well-being, neighborly interaction, social capita

Characterization of Pulmonary Metastases in Children With Hepatoblastoma Treated on Children\u27s Oncology Group Protocol AHEP0731 (The Treatment of Children With All Stages of Hepatoblastoma): A Report From the Children\u27s Oncology Group.

Purpose To determine whether the pattern of lung nodules in children with metastatic hepatoblastoma (HB) correlates with outcome. Methods Thirty-two patients with metastatic HB were enrolled on Children\u27s Oncology Group Protocol AHEP0731 and treated with vincristine and irinotecan (VI). Responders to VI received two additional cycles of VI intermixed with six cycles of cisplatin/fluorouracil/vincristine/doxorubicin (C5VD), and nonresponders received six cycles of C5VD alone. Patients were imaged after every two cycles and at the conclusion of therapy. All computed tomography scans and pathology reports were centrally reviewed, and information was collected regarding lung nodule number, size, laterality, timing of resolution, and pulmonary surgery. Results Among the 29 evaluable patients, only 31% met Response Evaluation Criteria in Solid Tumors (RECIST) for measurable metastatic disease. The presence of measurable disease by RECIST, the sum of nodule diameters greater than or equal to the cumulative cohort median size, bilateral disease, and ≥ 10 nodules were each associated with an increased risk for an event-free survival event ( P = .48, P = .08, P = .065, P = .03, respectively), with nodule number meeting statistical significance. Ten patients underwent pulmonary resection/metastasectomy at various time points, the benefit of which could not be determined because of small patient numbers. Conclusion Children with metastatic HB have a poor prognosis. Overall tumor burden may be an important prognostic factor for these patients. Lesions that fail to meet RECIST size criteria (ie, those \u3c 10 mm) at diagnosis may contain viable tumor, whereas residual lesions at the end of therapy may constitute eradicated tumor/scar tissue. Patients may benefit from risk stratification on the basis of the burden of lung metastatic disease at diagnosis

Role of Spinophilin in Group I Metabotropic Glutamate Receptor Endocytosis, Signaling, and Synaptic Plasticity

Activation of Group I metabotropic glutamate receptors (mGluRs) activates signaling cascades, resulting in calcium release from intracellular stores, ERK1/2 activation, and long term changes in synaptic activity that are implicated in learning, memory, and neurodegenerative diseases. As such, elucidating the molecular mechanisms underlying Group I mGluR signaling is important for understanding physiological responses initiated by the activation of these receptors. In the current study, we identify the multifunctional scaffolding protein spinophilin as a novel Group I mGluR-interacting protein. We demonstrate that spinophilin interacts with the C-terminal tail and second intracellular loop of Group I mGluRs. Furthermore, we show that interaction of spinophilin with Group I mGluRs attenuates receptor endocytosis and phosphorylation of ERK1/2, an effect that is dependent upon the interaction of spinophilin with the C-terminal PDZ binding motif encoded by Group I mGluRs. Spinophilin knock-out results in enhanced mGluR5 endocytosis as well as increased ERK1/2, AKT, and Ca2+ signaling in primary cortical neurons. In addition, the loss of spinophilin expression results in impaired mGluR5-stimulated LTD. Our results indicate that spinophilin plays an important role in regulating the activity of Group I mGluRs as well as their influence on synaptic activity

Reconciling conflicting evidence for the cause of the observed early 21st century Eurasian cooling

It is now well established that the Arctic is warming at a faster rate than the global average. This warming, which has been accompanied by a dramatic decline in sea ice, has been linked to cooling over the Eurasian subcontinent over recent decades, most dramatically during the period 1998–2012. This is a counter-intuitive impact under global warming given that land regions should warm more than ocean (and the global average). Some studies have proposed a causal teleconnection from Arctic sea-ice retreat to Eurasian wintertime cooling; other studies argue that Eurasian cooling is mainly driven by internal variability. Overall, there is an impression of strong disagreement between those holding the “ice-driven” versus “internal variability” viewpoints. Here, we offer an alternative framing showing that the sea ice and internal variability views can be compatible. Key to this is viewing Eurasian cooling through the lens of dynamics (linked primarily to internal variability with some potential contribution from sea ice; cools Eurasia) and thermodynamics (linked to sea-ice retreat; warms Eurasia). This approach, combined with recognition that there is uncertainty in the hypothesized mechanisms themselves, allows both viewpoints (and others) to co-exist and contribute to our understanding of Eurasian cooling. A simple autoregressive model shows that Eurasian cooling of this magnitude is consistent with internal variability, with some periods exhibiting stronger cooling than others, either by chance or by forced changes. Rather than posit a “yes-or-no” causal relationship between sea ice and Eurasian cooling, a more constructive way forward is to consider whether the cooling trend was more likely given the observed sea-ice loss, as well as other sources of low-frequency variability. Taken in this way both sea ice and internal variability are factors that affect the likelihood of strong regional cooling in the presence of ongoing global warming.</p

Preliminary acoustic and oceanographic observations from the ASIAEX 2001 South China Sea Experiment

The Asian Seas International Experiment (ASIAEX) was a very successful scientific collaboration between the United States of America (USA), the People’s Republic of China (PRC), Taiwan (ROC), the Republic of Korea (ROK), Japan, Russia, and Singapore. Preliminary field experiments associated with ASIAEX began in spring of 2000. The main experiments were performed in April-August, 2001. The scientific plan called for two major acoustics experiments, the first a bottom interaction experiment in the East China Sea (ECS) and the second a volume interaction experiment in the South China Sea (SCS). In addition to the acoustics efforts, there were also extremely strong physical oceanography and geology and geophysics components to the experiments. This report will concentrate on describing the moored component of the South China Sea portion of ASIAEX 2001 performed from the Taiwan Fisheries research vessel FR1 (Fisheries Researcher 1). Information on the environmental moorings deployed from the Taiwanese oceanographic research vessel OR1 (Oceanographic Researcher 1) will also be listed here for completeness, so that the reader can pursue later analyses of the data. This report does not pursue any data analyses per se.Funding was provided by the Office of Naval Research under Grant Numbers N00014-01-1-0772, N00014-98-1-0413 and N00014-00-1-0206