AMPT-induced monoamine depletion in humans: evaluation of two alternative [123I]IBZM SPECT procedures

Purpose Acute monoamine depletion paradigms using alpha-methyl-para-tyrosine (AMPT) combined with single photon emission computed tomography (SPECT) have been used successfully to evaluate disturbances in central dopaminergic neurotransmission. However, severe side effects due to relatively high doses (4,500 to 8,000 mg) of AMPT have been reasons for study withdrawal. Thus, we assessed the effectiveness and tolerability of two alternative procedures, using lower doses of AMPT. Methods Six healthy subjects underwent three measurements of striatal dopamine D2 receptor (D2R)-binding potential (BPND) with SPECT and the selective radiolabeled D2R antagonist [123I]IBZM. All subjects were scanned in the absence of pharmacological intervention (baseline) and after two different depletion procedures. In the first depletion session, over 6 h, subjects were administered 1,500 mg of AMPT before scanning. In the second depletion session, over 25 h, subjects were administered 40 mg AMPT/kg body weight. We also administered the Subjective Well-being Under Neuroleptic Treatment Scale, a self-report instrument designed to measure the subjective experience of patients on neuroleptic medication. Results We found no change of mean D2R BPND after the first and short AMPT challenge compared to the baseline. However, we found a significant increase in striatal D2R BPND binding after the AMPT challenge adjusted for bodyweight compared to both other regimen. Although subjective well-being worsened after the prolonged AMPT challenge, no severe side effects were reported. Conclusions Our results imply a low-dosage, suitable alternative to the common AMPT procedure. The probability of side effects and study withdrawal can be reduced by this procedure

Genomic organization and evolution of the Atlantic salmon hemoglobin repertoire

<p>Abstract</p> <p>Background</p> <p>The genomes of salmonids are considered pseudo-tetraploid undergoing reversion to a stable diploid state. Given the genome duplication and extensive biological data available for salmonids, they are excellent model organisms for studying comparative genomics, evolutionary processes, fates of duplicated genes and the genetic and physiological processes associated with complex behavioral phenotypes. The evolution of the tetrapod hemoglobin genes is well studied; however, little is known about the genomic organization and evolution of teleost hemoglobin genes, particularly those of salmonids. The Atlantic salmon serves as a representative salmonid species for genomics studies. Given the well documented role of hemoglobin in adaptation to varied environmental conditions as well as its use as a model protein for evolutionary analyses, an understanding of the genomic structure and organization of the Atlantic salmon α and β hemoglobin genes is of great interest.</p> <p>Results</p> <p>We identified four bacterial artificial chromosomes (BACs) comprising two hemoglobin gene clusters spanning the entire α and β hemoglobin gene repertoire of the Atlantic salmon genome. Their chromosomal locations were established using fluorescence <it>in situ </it>hybridization (FISH) analysis and linkage mapping, demonstrating that the two clusters are located on separate chromosomes. The BACs were sequenced and assembled into scaffolds, which were annotated for putatively functional and pseudogenized hemoglobin-like genes. This revealed that the tail-to-tail organization and alternating pattern of the α and β hemoglobin genes are well conserved in both clusters, as well as that the Atlantic salmon genome houses substantially more hemoglobin genes, including non-Bohr β globin genes, than the genomes of other teleosts that have been sequenced.</p> <p>Conclusions</p> <p>We suggest that the most parsimonious evolutionary path leading to the present organization of the Atlantic salmon hemoglobin genes involves the loss of a single hemoglobin gene cluster after the whole genome duplication (WGD) at the base of the teleost radiation but prior to the salmonid-specific WGD, which then produced the duplicated copies seen today. We also propose that the relatively high number of hemoglobin genes as well as the presence of non-Bohr β hemoglobin genes may be due to the dynamic life history of salmon and the diverse environmental conditions that the species encounters.</p> <p>Data deposition: BACs S0155C07 and S0079J05 (fps135): GenBank <ext-link ext-link-id="GQ898924" ext-link-type="gen">GQ898924</ext-link>; BACs S0055H05 and S0014B03 (fps1046): GenBank <ext-link ext-link-id="GQ898925" ext-link-type="gen">GQ898925</ext-link></p

Simple rules can guide whether land or ocean based conservation will best benefit marine ecosystems

Coastal marine ecosystems can be managed by actions undertaken both on the land and in the ocean. Quantifying and comparing the costs and benefits of actions in both realms is therefore necessary for efficient management. Here, we quantify the link between terrestrial sediment run-off and a downstream coastal marine ecosystem, and contrast the cost-effectiveness of marine and land-based conservation actions. We use a dynamic land- and sea-scape model to determine whether limited funds should be directed to one of four alternative conservation actions – protection on land, protection in the ocean, restoration on land, or restoration in the ocean – to maximise the extent of light-dependent marine benthic habitats, across decadal time-scales. We apply the model to a case study seagrass meadow in Australia. We find that marine restoration is the most cost-effective action over decadal time-scales in this system, based on a conservative estimate of the rate at which seagrass can expand into new habitat. The optimal decision will vary in different social-ecological contexts, but some basic information can guide optimal investments to counteract land and ocean based stressors: (1) marine restoration should be prioritised if the rates of marine ecosystem decline and expansion are similar and low; (2) marine protection should take precedence if the rate of marine ecosystem decline is high, or if the adjacent catchment is relatively intact and has a low rate of vegetation decline; (3) land-based actions are optimal when the ratio of marine ecosystem expansion to decline is >1.4, with terrestrial restoration typically the most cost effective; and (4) land protection should be prioritised if the catchment is relatively intact, but the rate of vegetation decline is high. These rules-of-thumb illustrate how cost-effective conservation outcomes for connected land-ocean systems can proceed without complex modelling

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A1 receptors (A1Rs) and the less abundant, but widespread, facilitatory A2ARs. It is commonly assumed that A1Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A1R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A1Rs in chronic noxious situations. In contrast, A2ARs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A2AR antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A2AR antagonists as novel protective agents in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, ischemic brain damage and epilepsy. The greater interest of A2AR blockade compared to A1R activation does not mean that A1R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A2AR antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A1Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different

ICAR: endoscopic skull‐base surgery

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Paleontology of leaf beetles

`The rate of evolution in any large group is not uniform; there are periods of relatise stability, and periods of comparatively rapid change.&apos; Cockerell and LeVeque, 1931 To Yenli Ych, my beloved wife, a most wonderful person! The fossil record of the Chrysomelidae can be tentatively traced back to the late Paleozoic to early Mesozoic Triassic. Mesozoic records at least 9 subfamilies, 19 genera, and 35 species, are represented by the Sagrinae, the exclusively Mesozoic Proto scelinae, Clytrinae, Cryptocephalinae, Eumolpinae, Chrysomelinae. Galerucinac, Alticinae, and Cassidinae. Cenozoic records at least 12 subfamilies- 63 % of the extant- 12! genera, and 325 species, include the same extant subfamilies as well as the Donaciinae, Zeugophorinae, Criocerinae, and Hispinae and can be frequently identified to genus, especially if preserved in amber. Quaternary records are often identified to extant species. tn total, at least t3! genera about 4 % of total extant, and 357 species &lt; 1 % have been reported. At least, 24 genera &lt;1 % of the extant seem to be extinct. Although reliable biological information associated with the fossil chrysomelids is very scarce, it seems that most of the modern host-plant associations were established, at least, in the late Mesozoic to early Cenozoic. As a whole, stasis seems to be the general rule of the chrysomelid fossil record. Together with other faunal elements, chrysomelids, especially donaciines, have been used as biogeographic and paleoclimatological indicators in the Holocene. I

Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions