The GPR88 orphan G protein-coupled receptor is expressed throughout the striatum, being preferentially localised in medium spiny neurons. It is also present in lower densities in frontal cortex and thalamus. Rare mutations in humans suggest a role in cognition and motor function, while common variants are associated with psychosis. Here we evaluate the influence of genetic deletion of GPR88 upon performance in translational tasks interrogating motivation, reward evaluation and cognitive function. In an automated radial arm maze ‘N-back’ working memory task, Gpr88 KO mice showed impaired correct responding, suggesting a role for GPR88 receptors in working memory circuitry. Associative learning performance was similar to wild-type controls in a touchscreen task but performance was impaired at the reversal learning stage, suggesting cognitive inflexibility. Gpr88 KO mice showed higher breakpoints, reduced latencies and lengthened session time in a progressive ratio task consistent with enhanced motivation. Simultaneously, locomotor hyperactivity was apparent in this task, supporting previous findings of actions of GPR88 in a cortico-striatal-thalamic motor loop. Evidence for a role of GPR88 in reward processing was demonstrated in a touchscreen-based equivalent of the Iowa gambling task. Although both Gpr88 KO and wild-type mice showed a preference for an optimum contingency choice, Gpr88 KO mice selected more risky choices at the expense of more advantageous lower risk options. Together these novel data suggest that striatal GPR88 receptors influence activity in a range of procedures integrated by prefrontal, orbitofrontal and anterior cingulate cortico-striatal-thalamic loops leading to altered cognitive, motivational and reward evaluation processes. 相似文献
The prevailing paradigm about the Quaternary ecological and evolutionary history of Central European ecosystems is that they were repeatedly impoverished by regional extinctions of most species during the glacial periods, followed by massive recolonizations from southern and eastern refugia during interglacial periods. Recent literature partially contradicts this view and provides evidence to re-evaluate this Postglacial Recolonization Hypothesis and develop an alternative one. We examined the long-term history of the flora of the Carpathian (Pannonian) Basin by synthesising recent advances in ecological, phylogeographical, palaeoecological and palaeoclimatological research, and analysing the cold tolerance of the native flora of a test area (Hungary, the central part of the Carpathian Basin). We found that (1) many species have likely occurred there continuously since before the Last Glacial Maximum (LGM); (2) most of the present-day native flora (1404 species, about 80%) can occur in climates as cold as or colder than the LGM (mean annual temperature ≤+3.5°C); and (3) grasslands and forests can be species-rich under an LGM-like cold climate. These arguments support an alternative hypothesis, which we call the Flora Continuity Hypothesis. It states that long-term continuity of much of the flora in the Carpathian Basin is more plausible than regional extinctions during the LGM followed by massive postglacial recolonizations. The long-term continuity of the region's flora may have fundamental implications not only for understanding local biogeography and ecology (e.g. the temporal scale of processes), but also for conservation strategies focusing on protecting ancient species-rich ecosystems and local gene pools. 相似文献
The ability toresynthesize ATP during recovery from ischemia is limited tothe size of endogenous pool of adenine nucleotides. CytosolicAMP-specific 5'-nucleotidase (5'-NT) plays a key role inATP degradation and hence the capacity for ATP resynthesis. We havesuggested (J. Clin. Invest. 93:40-49, 1994) that intracellular acidosis [intracellular pH(pHi)] is a potentinhibitor of 5'-NT under in vivo conditions. To test thishypothesis further, we used the hyperthyroid rat heart because we couldalter pHi during ischemiaand determine the consequences of lowerpHi on AMPaccumulation (by chemical assay) and ATP resynthesis (by31P nuclear magnetic resonancespectroscopy) during reperfusion. Global no-flow ischemiacaused pHi to decrease from 7.1 under well-oxygenated control perfusion to 6.7. We found thatdecreasing pHi further from pH 6.7 to 6.4 leads to increased accumulation (30%) of AMP duringischemia and to a 2.5-fold increase in ATP resynthesis duringreperfusion. Analysis of all known substrates, products, activators,and inhibitors of the 5'-NT suggests that 5'-NT isactivated primarily by Mg2+ andADP and is inhibited by H+. Thusthese observations provide evidence for a salutary effect ofintracellular acidosis on preserving the AMP pool due to inhibition of5'-NT and suggest a novel role ofH+ in protecting ischemic tissue. 相似文献
Estuaries are complex systems where environmental fluctuations occur over distinct timescales due to local meteorological and large-scale climatic factors. Consequently, studies with low temporal resolution and taxonomic coverage may fail to detect isotopic variations in basal sources, providing biased interpretations of isotope mixing models. We investigated the seasonal and El Niño Southern Oscillation (ENSO)-driven interannual variations in δ13C, δ15N and C:N values among distinct basal sources and their implications for mixing models interpretation in a subtropical estuary. δ13C variations among sources differed in their magnitude and timescales, being large enough to confound source-specific values. Macroalgae and POM δ13C varied seasonally, whereas ENSO effects prevailed for C3 and C4 salt marsh plants, highlighting the contrasting influence of local versus remote environmental drivers on short- and long-lived primary producers, respectively. Peaks of δ15N were detected for all sources during short-term anthropogenic nutrient inputs. Isotope mixing model comparisons showed that overlooking isotopic variations in basal sources under distinct ENSO conditions can cause misinterpretation of local trophic interactions and nutrient cycling. The present study contributes to design appropriate sampling delineations in highly variable aquatic environments, emphasizing the importance of comprehensive, long-term monitoring of estuarine primary producers to encompass environmental drivers of stable isotopic variations.
Basal activity of submaxillary gland (SMG) renin is high in female mice that carry the Rnrs allele and is induced to higher levels by treatment with dihydrotestosterone (DHT). To determine whether the difference in basal activity between high (Rnrs/Rnrs) and low (Rnrb/Rnrb) strains is due to enhanced sensitivity of Rnrs/Rnrs strains to endogenous androgen, we first studied the effect of several types of endocrine ablation on SMG renin in young female mice, and second, we removed normal androgen receptor protein by introducing the X-linked Tfm gene. Adrenalectomy with or without castration had no effect on basal SMG renin; hypophysectomy decreased basal renin activity 400-fold but did not abolish responsiveness to DHT. Loss of androgen receptor did not affect basal renin activity but did prevent enhancement by DHT. Basal and induced renin activities in L.AKR(Alll)/Cy, a congenic strain homozygous for Rnrs introduced from AKR/J into the background of C57L/J, an Rnrb/Rnrb type strain, are intermediate between levels observed in the original strains. We conclude that (1) the basal level of SMG renin is regulated directly or indirectly by some pituitary hormone(s) but not by androgen, (2) androgen induction of renin activity requires a normal androgen receptor, and (3) major gene(s) that regulate basal as well as induced SMG renin are in a circumscribed region of chromosome 1.This work has been aided by Grants GM26414 and AM03892 from the National Institutes of Health, a grant from the Texas affiliate of the American Heart Association, and by research contract NO1-CP33255 from the Division of Cancer Cause and Prevention, the National Cancer Institute. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care. 相似文献
Despite the importance of the recruitment process for small pelagic fish and the high economic importance of European sardine
(Sardina pilchardus, Walbaum 1792) in the Mediterranean Sea, knowledge on the distribution and environmental characteristics of its nursery grounds
is very limited. In the present study, we used pelagic trawl data collected during 1995–2006 to explore the spatial distribution
of sardine juveniles in the Aegean Sea in early summer. Based on sardine abundance per length class, a cluster analysis was
initially used to define hauls dominated by juveniles. In a subsequent step, Discriminant Function Analysis (DFA) was applied
to discriminate stations with high relative abundance of juveniles using satellite environmental data and bottom depth. The
parameters contributing mostly to the discrimination of juvenile grounds were sea level anomaly, photosynthetically active
radiation, sea surface temperature, chlorophyll-α and bottom depth. The classification functions of DFA were finally used
to post classify unsampled areas in the Greek Seas and the Mediterranean Sea in order to map grounds that meet characteristic
environmental conditions for young sardine. Such areas were mostly located inshore, in semi-closed productive areas and often
in proximity to river mouths, a pattern that is generally supported by existing information.
Guest editor: V. D. Valavanis
Essential Fish Habitat Mapping in the Mediterranean 相似文献
Following the recent identification of the naturally occurring 3-ylidene-4,5-dihydrophthalide ligustilide and its oxidation product dehydroligustilide as novel TRPA1 modulators, a series of seventeen 3-ylidenephthalides was synthesized and tested on TRPA1 and TRPM8 channels. Most of these compounds acted as strong modulators of the two channel types with EC50 and/or IC50 values distinctly lower than those of the reference compounds. 相似文献