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Understanding the response of Himalayan glaciers to global warming is vital because of their role as a water source for the Asian subcontinent. However, great uncertainties still exist on the climate drivers of past and present glacier changes across scales. Here, we analyse continuous hourly climate station data from a glacierized elevation (Pyramid station, Mount Everest) since 1994 together with other ground observations and climate reanalysis. We show that a decrease in maximum air temperature and precipitation occurred during the last three decades at Pyramid in response to global warming. Reanalysis data suggest a broader occurrence of this effect in the glacierized areas of the Himalaya. We hypothesize that the counterintuitive cooling is caused by enhanced sensible heat exchange and the associated increase in glacier katabatic wind, which draws cool air downward from higher elevations. The stronger katabatic winds have also lowered the elevation of local wind convergence, thereby diminishing precipitation in glacial areas and negatively affecting glacier mass balance. This local cooling may have partially preserved glaciers from melting and could help protect the periglacial environment.

The Slender-billed Gull (Larus genei)breeds with a scattered distribution on an extensive nesting area, ranging from India and Afghanistan in the East to the Iberian Peninsula in the West, including the Mediterranean and the Black Sea. A number of habitats are used for breeding, such as sand-spits and beaches along coasts and islands of land-locked seas, steppe lakes, but also brackish or freshwater lagoons near river deltas. Sea level rise dramatically affects coastal sites, thus being the greatest threat to the survival of many seabird species, including gulls. This note describes habitat selection, breeding success and causes of failure of Slender-billed Gulls during their colonisation of the northern Po Delta (NE Italy) during 2018–2022. Slender-billed Gulls colonised the northern Po Delta in 2018. Six colonies were found during the study period. Birds used both natural barrier islands and artificial dredge islands. Productivity in the first five years after the colonisation event was zero, mostly due to colony sites being flooded by high tides and storms. If Slender-billed Gulls will switch to nest in nearby fish farms, these could provide plenty of suitable breeding sites, safe from tidal flooding and with very low predation pressure, allowing sufficient productivity. At the moment, Slender-billed Gulls are unsuccessful in colonising the barrier islands of the Po Delta.

In the last decade, the use of drones has proven to be the major innovation for studying various aspects of waterbird breeding biology, overcoming the environmental obstacles inherent in monitoring their breeding sites. The Squacco Heron (Ardeola ralloides)represents an example of the aforementioned difficulties, since it nests in impenetrable reed beds and nearby bushes, trees and shrubs. The present work reports the results of drone assessment of nest counting and reproductive success of the Squacco Heron in a colony in the Po Delta (NE Italy). At the beginning of the breeding season, far more nests (46) were found using drones than by eye from the nearest embankment (12). After four weeks (estimated hatching period), only ten nests were relocated by drone, due to vegetation overgrowth. All relocated nests were placed directly either within reed beds or on lower branches of shrubs, but always without higher branches obstructing the view from above. Finally, in the fledging period, no nest was relocated on drone imagery, due to further vegetation growth. Only 27 juveniles were found by drone, mostly perching on the canopy, without any evidence of nest failure, suggesting a critical underestimation. In conclusion, drone use improves accuracy of counting nesting Squacco Herons, but fails to assess productivity.

Background: Vortioxetine hydrobromide (VXT), a new therapeutic option in the treatment of major depressive disorder, is a poorly soluble drug, and instability under stress conditions has been reported. The aim of the present study was to prepare VXT liposomes (VXT-Ls) with an antidepressant-like effect, to improve drug stability and reduce toxicity of the free drug. Methods: Liposomes were prepared using the thin lipid film hydration method and properly characterized. Forced degradation studies were conducted in photolytic and oxidative conditions. The cytotoxicity was evaluated in VERO cells through MTT assay and in vivo toxicity was assessed in mice. The antidepressant-like effect in mice was confirmed using the open-field test paradigm and tail suspension test. Results: The optimized VXT-Ls have multilamellar vesicles with an average size of 176.74 nm ± 2.43. The liposomal formulation increased the stability of VXT. VERO cell viability was maintained at around 40% when the VXT-Ls were tested at higher concentrations and no signs of acute toxicity were observed in mice. The antidepressant-like effect was effective, for VXT-Ls, at doses ranging from 2.5 mg/kg to 10 mg/kg, measured by the tail suspension test in mice. The non-liposomal formulation was effective at a dose of 10 mg/kg. The open field test was performed and any unspecific changes in locomotor activity were revealed. Conclusions: Liposomes seem to be a promising alternative for an oral VXT formulation at lower doses (2.5 mg/kg). Graphical abstract:

The temporary or permanent chemical modification of biomolecules is a crucial aspect in the physiology of all living species. However, while some modules are well characterised also in insects, others did not receive the same attention. This holds true for sulfo-conjugation that is catalysed by cytosolic sulfotransferases (SULT), a central component of the metabolism of endogenous low molecular weight molecules and xenobiotics. In particular, limited information is available about the functional roles of the mosquito predicted enzymes annotated as SULTs in genomic databases. The herein described research is the first example of a biochemical and structural study of a SULT of a mosquito species, in general, and of the malaria vector Anopheles gambiaein particular. We confirmed that the AGAP001425 transcript displays a peculiar expression pattern that is suggestive of a possible involvement in modulating the mosquito reproductive tissues physiology, a fact that could raise attention on the enzyme as a potential target for insect-containment strategies. The crystal structures of the enzyme in alternative ligand-bound states revealed elements distinguishing AgSULT-001425 from other characterized SULTs, including a peculiar conformational plasticity of a discrete region that shields the catalytic cleft and that could play a main role in the dynamics of the reaction and in the substrate selectivity of the enzyme. Along with further in vitrobiochemical studies, our structural investigations could provide a framework for the discovery of small-molecule inhibitors to assess the effect of interfering with AgSULT-001425-mediated catalysis at the organismal level.

The emission of greenhouse gases from the enteric fermentation of ruminants contributes to the worsening of the world climate and has serious consequences for the environment. The use of additives in animal diets modulates the population of rumen microorganisms, reduces metabolic losses through methanogenic pathways, and brings benefits in improving the energy balance of volatile fatty acids in the rumen, but, the traditional antibiotics, increase the risk of contamination to the environment and antimicrobial resistance. Fator P is a natural additive composed of amino acids (lysine, methionine, and tyrosine), choline, minerals, probiotics and essential fatty acids (omega 3 and omega 6). The advantage of using the natural additive Fator P, is that it can reduce the risk of antimicrobial resistance, maintain the balance of the ruminal ecosystem, and avoid possible destabilization of the flora even with constant use of the additive. The aim of this study was to quantify methanogenic microorganisms in grazing animals treated with the additive Factor P, and show that the additive is able to reduce and maintain the methanogenic population stable for a period of 365 consecutive days. The experiment was conducted using 3 cattle per treatment randomized based on the initial methanogenic population, that received a daily dose of 6 g of Factor P additive in the treated group, and 6 g of placebo in the control group. Samples of ruminal fluids from the animals were collected weekly for DNA extraction (Qiagem 51604). The evaluation of the profile of methanogenic microorganisms was performed by the relative quantification method using qPCR with primer sequences for total bacteria and methanogenic (target) bacteria, described in the literature and previously standardized in calibration curves. The statistics analyzes were performed according to the ANOVA test followed by the Tukey mean test (P <0.05) in GraphPad PRISM Program 7.00 version. These results of the difference between the means of the weekly relative quantifications of the treated group (0.197) and control group (0.279), showed a reduction of 29.9% (Pvalue = 0.0022; Table 1). The results indicate that the natural additive Fator P is an efficient and sustainable product for reducing and maintaining the methanogenic population of the treated group stable throughout the 365 days of the year. In this case, it can be considered as a safe solution to reduce the methanogenic population and has been shown to be effective in increasing the productivity of commercial cattle.

The use of additives in the diet of ruminants consists of a management protocol that makes the livestock system more productive, sustainable and profitable. In practice, additives promote the balance of the microbial population, and improve the energy balance from food. The use of these compounds becomes advantageous as they reduce energy losses by methanogenic metabolic pathways, and the emission of enteric gases from ruminal fermentation. The short-chain fatty acids which are compounds resulting from rumen fermentation, constitute the main source of energy in the rumen, and therefore, the entire metabolic process can directly reflect the productivity performance of the cattle. Fator P is a natural additive composed of amino acids, minerals, probiotics, prebiotics and fatty acids, which was developed to meet current market needs. The aim of this study was to evaluate the synthesis of short-chain fatty acids from ruminal fluid collected from grazing animals treated with the Fator P additive over a period of 365 consecutive days. The ruminal metabolism work was conducted at Research Center of Premix (Patrocínio Paulista-SP, Brazil), using 3 cattle per treatment, which received a daily dose of 6 g of Fator P additive in the treated group, and 6 g of placebo in the control group. Ruminal fluid samples were collected weekly, and the analysis of short-chain fatty acids were carried out by the method of gas chromatography coupled to mass spectrometry. The results of the difference between means showed an increase of 15.2% (P< 0.0001) in the production of total fatty acids in the group treated with the natural additive Fator P compared with the control group. Notably, there was also an increase in the production of the three main AGCC: 13.3% for acetate (P< 0.0001); 14.7% for propionate (P= 0.0003); and 18.4% for butyrate (P= 0.0001; Table 1). Statistical analyzes were performed using the ANOVA test followed by the Tukey mean test (P< 0.05) in GraphPad PRISM Program 7.00 version. Therefore, the results indicate that the natural additive Fator P improves energy levels through the increase of short-chain fatty acids and directly reflects on the productivity indexes of the cattle. Furthermore, the product reduces the use of growth promoting antibiotics, improve intestine health, immune response of animals, carcass finishing, increase herd weight gain and milk production in a profitable and sustainable way for the cattle breeder.

Agriculture is peculiar among other industries because supply risk, either through weather or perishability, challenges vertical coordination between independent farmer suppliers and commodity buyers. Moreover, production of agricultural commodities is strictly focused in some regions while there are others who rely mainly on commodities imports. The objective of this study is to provide a comprehensive understanding of the commodity market structure and how its features impact the supply chain organisation and companies' strategies. Specifically, the main sources of risks relative to wheat, corn and soybean commodities markets are investigated and related to international trade and supply chain relationships. Furthermore, attention is given to strategies and capabilities that companies working in this market implement to hedge their risks. The evidence provided is based on the case studies of two intermediaries operating in the cereal supply chain, based in USA and Europe.

Background: Irinotecan (IRI) is a widely used chemotherapeutic drug, mostly used for first-line treatment of colorectal and pancreatic cancer. IRI doses are usually established based on patient’s body surface area, an approach associated with large inter-individual variability in drug exposure and high incidence of severe toxicity. Toxic and therapeutic effects of IRI are also due to its active metabolite SN-38, reported to be up to 100 times more cytotoxic than IRI. SN-38 is detoxified by the formation of SN-38 glucuronide, through UGT1A1. Genetic polymorphisms in the UGT1A1 gene are associated to higher exposures to SN-38 and severe toxicity. Pharmacokinetic models to describe IRI and SN-38 kinetic profiles are available, with few studies exploring pharmacokinetic and pharmacogenetic-based dose individualization. The aim of this manuscript is to review the available evidence supporting pharmacogenetic and pharmacokinetic dose individualization of IRI in order to reduce the occurrence of severe toxicity during cancer treatment. Methods: The PubMed database was searched, considering papers published in the period from 1995-2017, using the keywords irinotecan, pharmacogenetics, metabolic genotyping, dose individualization, therapeutic drug monitoring, pharmacokinetics and pharmacodynamics, either alone or in combination, with original papers being selected based on the presence of relevant data. Conclusion: The findings of this review confirm the importance of considering individual patient characteristics to select IRI doses. Currently, the most straightforward approach for IRI dose individualization is UGT1A1 genotyping. However, this strategy is sub-optimal due to several other genetic and environmental contributions to the variable pharmacokinetics of IRI and its active metabolite. The use of dried blood spot sampling could allow the clinical application of limited sampling and population pharmacokinetic models for IRI doses individualization.

AbstractThis trial evaluates the feasibility of using passive injectable transponders (PITs) in field operations by testing identification procedures on 185 one-year-old Biellese ewes reared under nomadic farming conditions. Commercial PITs of 3.85 ± 0.05 mm × 31.2 mm were used at two application sites, the armpit and the retro-auricular region. The two application sites were compared taking into account the ease of injection, animal reaction, injection duration, inflammatory response, PIT readability at up to 12 months post-injection and PIT recovery at the slaughterhouse. The injection site influenced the reaction of the animal and the ease and duration of the injection, but it did not affect the palpation and the reading findings during the rearing period. The injection site also influenced the PIT retrieval at the slaughterhouse depending on the operator who recovered the PIT. The readability values observed at the end of the observation period for both injection sites (83% in the retro-auricular region and 79% in the armpit region) were too low to be suitable for long-term animal identification. In addition, the failed retrieval of PITs at slaughter, determined the destruction of 40 (22%) carcases to avoid any risks in the food chain. These findings suggest that the limited use of PITs is indicated when other methods of electronic identification cannot be employed, while a wider application of the device tested in the present study is not recommended in farming practices.

ABSTRACTInstrumental records indicate a warming of approximately 0.8 °C has occurred in the Mount Everest region since the 1980s, which has resulted in a 100–300 m rise in the height at which the ground is permanently frozen as well as a retreat and thinning of Everest’s glaciers. For some time, there have been concerns that this warming and the resultant changes in the region’s glaciers may be increasing the risks for travellers to Mount Everest as well as the indigenous populations who support them. On 18 April 2014, an avalanche caused by the collapse of a large serac swept down Mount Everest’s Khumbu Ice Fall resulting in the deaths of 16 Sherpa. Although satellite imagery has been used to estimate the size of the serac, in situ data on the avalanche itself has not been available. Here we show that this event coincided with an approximate 15-min-long wind, thermal, and moisture anomaly, which was observed at the Nepal Climate Observatory-Pyramid situated 10 km from Mount Everest. We argue that this anomaly was associated with the avalanche and thereby provides some information on its scale and duration as well as a potential mechanism to monitor future events in this remote and data-sparse region.

Background: The taxane drugs paclitaxel and docetaxel, widely used on cancer chemotherapy, are currently dosed mainly based on body-surface area. This approach is associated with wide interindividual variability in drug exposure, leading to suboptimal dosing for many patients. Methods: The available evidence supporting dose individualization strategies for paclitaxel and docetaxel were reviewed, focusing mainly on the application of therapeutic drug monitoring by a priori pharmacogenetic data or a posteriori drug measurements in biological fluids. The PubMed database was searched, in the period of 1987-2017, using the keywords pharmacogenetics, metabolic genotyping, dose individualization, therapeutic drug monitoring, personalized medicine, taxanes paclitaxel and docetaxel, either alone or in combination. Results: The current knowledge of pharmacology of the taxane drugs paclitaxel and docetaxel, mainly its pharmacokinetics and the proteins responsible for their biotransformation and transport, along with the genetic polymorphism responsible for variations in the activities of these proteins, opens new opportunities for dose selection for individual patients. Conclusion: Considering the relation between systemic exposure to these drug and clinical responses, a posteriori TDM, with measurement of drug concentrations in plasma of treated patients, is currently the most straightforward approaches for dose individualization of paclitaxel and docetaxel.

A brood of laying hens infested with the lice Menacanthus cornutus(Phthiraptera: Menoponidae) evidenced itching, irritation, and damage to their zootechnical performance. A study was conducted to evaluate the zootechnical performance and infestation control using a 1% solution of fluralaner in a brood of white laying hens infested naturally with lice. The experiment was carried out using 10,560 naturally infested chickens divided into 2 groups: a treatment group of animals that received a 1% solution of fluralaner in drinking water, at a dose of 0.05 mL/kg of body weight, in 2 administrations, 7 d apart; and a control group of infested and untreated chickens. The groups of chickens were followed for 120 d to evaluate the score of infestation and zootechnical performance. It was observed that birds in the treatment group became free of lice infestation 7 d after the administration of the first dose of a 1% solution of fluralaner. For up to 120 d after the experiment was initiated, there was no evidence of subsequent lice infestation, while continued infestation with all life stages of lice (adults, young, or eggs) was evident in the untreated control group, remaining stable during all evaluations performed. The birds in the treatment group showed improved zootechnical performance when compared to a 9.94% egg production decrease in the control group. The feed conversion and egg mass data showed statistically significant differences between the 2 groups. This study allows us to conclude that treatment with a 1% solution of fluralaner effectively controlled Menacanthus cornutuslice infestation and promoted recovery of egg production in a brood of laying hens treated with the test formulation.

This study aims at the examination of the way the creative behaviours are displayed in the pubescent and adolescents with mental disability, as compared to the ones with normal intellect. The display of these behaviours is important in order to increase their adjustment capacity.

The article purports to approach a less studied theme in Romania, which is the quality of the institutionalised mentally retarded adults’ life in large residential centres. Quality of Life Questionnaire was used to determine life satisfaction, competence, independence and community integration of participants. Aberrant Behaviour (irritability, lethargy, stereotypy, hyperactivity and inappropriate speech) was assessed using Aberrant Behaviour Checklist –Community. Data obtained allowed us to conclude that the negative effects the large institutions have on the quality of life of people with disabilities and also on their behaviour could be reduced by providing an environment similar to a family type (small centers).

In the specialised literature, most studies have analysed language by relating it to the level of intellectual development and the quality of educational influences. We believe that the specificity of the language used by mentally deficient children may be fully elucidated only by considering of the two references above. We have studied aspects concerning language productivity, the quality of expression and verbal coherence, we have analysed the comprehension capacity and the possibility of using the information accumulated so that, in the end, we could be able elaborate a language development program adapted to the gender of the subjects.

Foster homes or foster care centres provide different conditions for the evolution of institutionalised subjects, which emphasize a behavioural and personality type somewhat different in comparison to regular life style situations. As such, affectivity and communication are the most sensitive elements to the life environment that does not always have favourable effects upon the subjects’ psychic evolution. The purpose of this study is that of underlining the dimension of the institutionalised environment upon the birth and evolution of communicational and affective structures, as well as emphasizing the distortions of communication and affectivity as an effect of the institutionalised environment.

In diabetic patients the incidence of cardiovascular diseases (CVD) is higher compared with those without diabetes. This elevated incidence may be due to an increased prevalence of established risk factors, such as obesity, dyslipidemia and hypertension. However, several other determinants must be considered. Attention must be paid to the role that specific factors strictly related to diabetes, insulin- resistance and post-prandial hyperglycemia, play in the etiopathogenesis of CVD, as for example atherosclerosis. This review acknowledges the incidence of diabetes on cardiovascular diseases and atherosclerosis from endothelial dysfunction to plaque destabilization, suggesting that insulin resistance and postprandial hyperglycemia should be considered keys in the generation of these worst diabetic cardiovascular outcomes. It finds in hyperglycemia the primum movens that mediates the cascade of vascular damaging events from the beginning of ROS formation to plaque rupture, through increased inflammation. It also adds insights of why diverse therapeutic interventions, which have in common the ability to reduce oxidative stress and inflammation, can impede or delay the onset of complication of atherosclerosis in diabetic patients.

The transcriptome-wide endosperm-preferred expression of maize genes was addressed by analyzing a large database of expressed sequence tags (ESTs). We generated 30,531 high quality sequence-reads from the 5′-ends of cDNA libraries from maize endosperm harvested at 10, 15, and 20 days after pollination. A further 196,900 maize sequence-reads retrieved from public databases were added to this endosperm collection to generate MAIZEST, a database with tools for data storage and analysis. MAIZEST contains 227,431 ESTs, one third of which represents developing endosperm and the remaining two-thirds represent transcripts from 49 cDNA libraries constructed from different organs and tissues. Assembling the MAIZEST ESTs generated 29,206 putative transcripts, of which a set of 4032 assembled sequences was composed exclusively of sequences derived from endosperm cDNA libraries. After sequence analysis using overlapping parameters, a sub-set of 2403 assembled sequences was functionally annotated and revealed a wide variety of putative new genes involved in endosperm development and metabolism.

alpha-Haemolysin is an extracellular protein toxin (107KDa) produced by certain pathogenic strains of Escherichia coli. It can bind to lipid bilayers and produce membrane disruption in cell and model membranes. Protein secondary structure predictions suggest an amphipathic helix conformation for the membrane-interacting domain of HlyA, and no potential transmembrane segments. In this paper, we investigated the lipid associating properties of the chemically synthesized peptide H9 (MFEHVASKMADVIAEWEK) corresponding to residues 417-434 of HlyA. Changes in the intrinsic fluorescence and fluorescence anisotropy of the single Trp residue after the addition of DMPC-LUV reveal that the peptide-membrane interaction is optimum at or above the gel-liquid crystalline transition temperature of the lipid. Moreover, the peptide induces vesicle aggregation, as detected through changes in light scattering by the vesicle suspension. However, under comparable conditions, H9 has no hemolytic activity against sheep erythrocytes, nor does it induce leakage of vesicular aqueous contents. These data suggest that HlyA binds the membrane surface through amphipathic helices, though cooperativity among neighbouring helices is probably necessary to explain the lytic effect of the toxin.

alpha-Haemolysin is an extracellular protein toxin (107KDa) produced by certain pathogenic strains of Escherichia coli. It can bind to lipid bilayers and produce membrane disruption in cell and model membranes. Protein secondary structure predictions suggest an amphipathic helix conformation for the membrane-interacting domain of HlyA, and no potential transmembrane segments. In this paper, we investigated the lipid associating properties of the chemically synthesized peptide H9 (MFEHVASKMADVIAEWEK) corresponding to residues 417-434 of HlyA. Changes in the intrinsic fluorescence and fluorescence anisotropy of the single Trp residue after the addition of DMPC-LUV reveal that the peptide-membrane interaction is optimum at or above the gel-liquid crystalline transition temperature of the lipid. Moreover, the peptide induces vesicle aggregation, as detected through changes in light scattering by the vesicle suspension. However, under comparable conditions, H9 has no hemolytic activity against sheep eryth rocytes, nor does it induce leakage of vesicular aqueous contents. These data suggest that HlyA binds the membrane surface through amphipathic helices, though cooperativity among neighbouring helices is probably necessary to explain the lytic effect of the toxin.

Abstract: The influence of vanadate on the adsorption properties of Merocyanine 540 (MC540) to UMR cells was studied by means of specrofluorometry. An increment in the fluorescence was observed in the osteoblasts incubated with 0.1 mM vanadate. This effect could be interpreted in terms of vanadate inhibitory effects on aminotraslocase activity. However, vanadate promotes a similar behavior to that found in UMR 106 cells when it was added to lipid vesicles composed of phosphatidylcholine. The effect of vanadium in different oxidation states, such as vanadate(V) and vanadyl(IV) on lipid membrane properties was examined in large unilamellar vesicles by means of spectrofluorometry employing different probes. Merocyanine 540 and 1,6-diphenylhexatriene were used in order to sense the changes at interfacial and hydrophobic core of membranes, respectively. In contrast to vanadate, vanadyl decreased the fluorescence of MC540. Both vanadium compounds slightly perturbed the hydrocarbon core. The results can be interpreted by the specific adsorption of both compounds on the polar head groups of phospholipid and suggest a possible influence of vanadium compounds on the lipid organization of cell membranes.

The novel quinoline-2-carboxamide derivatives N-[methyl-¹¹C]-3-methyl-4-phenyl-N-(phenylmethyl)quinoline-2-carboxamide ([¹¹C]4), (±)-N-[methyl-¹¹C]-3-methyl-N-(1-methylpropyl)-4-phenylquinoline-2-carboxamide ([¹¹C]5), and (±)-N-[methyl-¹¹C]-3-methyl-4-(2-fluorophenyl)-N-(1-methylpropyl)quinoline-2-carboxamide ([¹¹C]6) were labeled with carbon-11 (t1/2 = 20.4 min, β⁺ = 99.8%) as potential radioligands for the noninvasive assessment of peripheral benzodiazepine type receptors (PBR) in vivo with positron emission tomography (PET). The radiosynthesis consisted of N-methylation of the desmethyl precursors 3-methyl-4-phenyl-N-(phenylmethyl)quinoline-2-carboxamide (4a), (±)-3-methyl-N-(1-methylpropyl)-4-phenylquinoline-2-carboxamide (5a), and (±)-4-(2-fluorophenyl)-3-methyl-N-(1-methylpropyl)quinoline-2-carboxamide (6a) with either [¹¹C]methyl iodide or [¹¹C]methyl triflate in the presence of tetrabutylammonium hydroxide or potassium hydroxide in dimethylformamide. The radioligands [¹¹C]4, [¹¹C]5, and [¹¹C]6 were synthesized with over 99% radiochemical purity in 30 min, 30 ± 5% radiochemical yield, calculated at the end of synthesis (EOS) non-decay-corrected, and 2.5 ± 1.2 Ci/μmol of specific radioactivity. Inhibition studies in rats following intravenous pre-administration of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11195, 1) showed high specific binding to PBR of [¹¹C]4, [¹¹C]5, and [¹¹C]6 in heart, lung, kidney, adrenal gland, spleen, and brain. The biological data suggest that [¹¹C]5, [¹¹C]6, and particularly [¹¹C]4 are promising radioligands for PBR imaging in vivo with PET.