A missense mutation (c.184C > T) in ovine CLN6 causes neuronal ceroid lipofuscinosis in Merino sheep whereas affected South Hampshire sheep have reduced levels of CLN6 mRNA

The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are a group of fatal recessively inherited neurodegenerative diseases of humans and animals characterised by common clinical signs and pathology. These include blindness, ataxia, dementia, behavioural changes, seizures, brain and retinal atrophy and accumulation of fluorescent lysosome derived organelles in most cells. A number of different variants have been suggested and seven different causative genes identified in humans (CLN1, CLN2, CLN3, CLN5, CLN6, CLN8 and CTSD). Animal models have played a central role in the investigation of this group of diseases and are extremely valuable for developing a better understanding of the disease mechanisms and possible therapeutic approaches. Ovine models include flocks of affected New Zealand South Hampshires and Borderdales and Australian Merinos. The ovine CLN6 gene has been sequenced in a representative selection of these sheep. These investigations unveiled the mutation responsible for the disease in Merino sheep (c.184C > T; p.Arg62Cys) and three common ovine allelic variants (c.56A > G, c.822G > A and c.933_934insCT). Linkage analysis established that CLN6 is the gene most likely to cause NCL in affected South Hampshire sheep, which do not have the c.184C > T mutation but show reduced expression of CLN6 mRNA in a range of tissues as determined by real-time PCR. Lack of linkage precludes CLN6 as a candidate for NCL in Borderdale sheep.     

Effects of salinity on hard clam (Mercenaria mercenaria) defense parameters and QPX disease dynamics

QPX (Quahog Parasite Unknown) is a protistan parasite affecting hard clams (Mercenaria mercenaria) along the Northeast coast of the United States. The fact that QPX disease epizootics are usually observed in field sites with high salinities led to the general assumption that salinity represents an important factor for disease distribution. This study was designed to investigate the effect of salinity on QPX disease development as well as constitutive and QPX-induced defense factors in M. mercenaria. Naïve and QPX-infected (both experimentally and naturally) clams were submitted to 17 and 30 psu for 4 months. Standard and QPX-specific cellular and humoral defense parameters were assessed after 2 and 4 months. These included total and differential hemocyte counts, reactive oxygen species production, phagocytic activity of hemocytes, lysozyme concentration in plasma, anti-QPX activity in plasma and resistance of hemocytes to cytotoxic QPX extracellular products. Results demonstrated higher QPX-associated mortality in naturally infected clams maintained at high salinity compared to those held at 17 psu. Our findings also showed an increase in mortality following experimental challenge with QPX in clams submitted to 30 psu but not in those held at 17 psu. Constitutive clam defense factors and the response to QPX challenge were also affected by salinity. QPX challenge caused significant but transitory changes in hemolymph parameters that were obvious at 2 months but disappeared at 4 months. Overall, our results show that salinity modulates clam immunity and the progress of QPX disease although its impact appears secondary as compared to findings we reported earlier for temperature.     

The neuronal ceroid-lipofuscinoses: A historical introduction

The neuronal ceroid-lipofuscinoses (Batten disease) collectively constitute one of the most common groups of inherited childhood onset neurodegenerative disorders, and have also been identified in many domestic and laboratory animals. The group of human neuronal ceroid-lipofuscinoses currently comprises 14 genetically distinct disorders, mostly characterised by progressive mental, motor and visual deterioration with onset in childhood or adolescence. Abnormal autofluorescent, electron-dense granules accumulate in the cytoplasm of nerve cells, and this storage process is associated with selective destruction and loss of neurons in the brain and retina. The present paper outlines nearly 200 years of clinical, neuropathological, biochemical and molecular genetic research, gradually leading, since 1995, to the identification of 13 different genes and over 360 mutations that underlie these devastating brain disorders and form the basis of a new classification system. These genes are evidently of vital importance for the normal development and maintenance of cerebral neurons. Elucidation of their functions and interactions in health and disease is a prerequisite for the identification of possible therapeutic targets, but may also further our understanding of the basic mechanisms of neurodegeneration and ageing. An account is also given of the development of international cooperation and free access electronic resources facilitating NCL research. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.     

Clinical characteristics of tumors derived from colorectal cancer patients who harbor the Tumor Necrosis Factor α-1031T/T and NOD2 3020insC polymorphism

Background: Genetic predispositions to disease have focused on highly penetrant causative changes in tumor suppressor genes or genes associated with DNA mismatch repair. New investigations are revealing new genetic associations with disease that are more subtle in their association with disease and require characterization. Methods: In this report we have examined the tumor characteristics in a group of patients who have been shown to harbor two polymorphisms in two genes that are associated with the immune system NOD2 and TNFα. Results: Colorectal cancers from patients with NOD2 3020insC and TNFα-1031T/T constitutional changes are mostly right-sided disease (OR = 2.21, p = 0.03) with a tendency to higher stages (OR = 2.41, p = 0.06), increased number of associated polyps (OR = 1.77, p = 0.16) and later age of average age of disease onset (p = 0.039). Conclusion: The results reveal that there appear to be specific characteristics associated with the tumors that may aid in determining management strategies to reduce the risk of disease.     

Norms of vagal nerve activity,indexed by Heart Rate Variability,in cancer patients

Recent research has begun to show the role of the activity of the vagus nerve in cancer prognosis. However, it remains unknown whether cancer severity can impair vagal nerve activity. This study combined data (N = 657) of five different cancers (colorectal, pancreas, prostate, lung and ovarian) concerning patients’ Heart Rate Variability (HRV), a vagal nerve activity index. These data were compared to HRV levels of a healthy sample in another study. In addition, we examined the moderating effects of age, gender and cancer stage on HRV. The mean HRV of the cancer patients sample was significantly lower (HRV = 22 ms) compared to the healthy sample (HRV = 50 ms) (p < 0.000001). While age and gender did not significantly affect HRV, cancer patients with advanced stages had significantly lower HRV than those with early stages (p = 0.011). A possible bi-directional relation between cancer and vagal nerve activity is discussed. These findings are of importance for prognostication since they provide researchers and clinicians with expected values of vagal nerve activity in cancer patients.     

Synthesis,molecular docking and α-glucosidase inhibition of 5-aryl-2-(6′-nitrobenzofuran-2′-yl)-1,3,4-oxadiazoles

Twenty derivatives of 5-aryl-2-(6′-nitrobenzofuran-2′-yl)-1,3,4-oxadiazoles (1–20) were synthesized and evaluated for their α-glucosidase inhibitory activities. Compounds containing hydroxyl and halogens (1–6, and 8–18) were found to be five to seventy folds more active with IC₅₀ values in the range of 12.75 ± 0.10–162.05 ± 1.65 μM, in comparison with the standard drug, acarbose (IC₅₀ = 856.45 ± 5.60 μM). Current study explores the α-glucosidase inhibition of a hybrid class of compounds of oxadiazole and benzofurans. These findings may invite researchers to work in the area of treatment of hyperglycemia. Docking studies showed that most compounds are interacting with important amino acids Glu 276, Asp 214 and Phe 177 through hydrogen bonds and arene-arene interaction.     

Predominance of terrestrial organic matter in sediments from a cyanobacteria- blooming hypereutrophic lake

Although an understanding of the quantity and quality of sedimentary organic matter (SOM) pools is necessary to design sound environmental management strategies for lacustrine systems, the characterization of organic matter sources and the assessment of their relative contributions to eutrophic and inland lake sediments remain insufficient. In this study, the contribution of potential organic matter sources to sediments in shallow and hypereutrophic lake Taihu, China was assessed on the molecular level using source-specific fatty acid biomarkers. The results indicated that SOM was composed mainly of terrestrial plants with a maximal contribution of 45.3 ± 2.4% to the total organic carbon, which accounted for approximately 66% among the determined organic matter sources. Evidence suggests the terrestrial plants remained in a fresh state in surface sediments: the correlation (R² = 0.62, p < 0.05) between bacterial and terrestrial plant carbon was strong. On the other hand, aquatic plant and bacterial carbon contributed 5–15% to the total organic carbon, which was followed by the faint contribution (<5% of total organic carbon) of algae-derived organic carbon including cyanobacteria, diatoms, and dinoflagellates. The results provided details of the contributions of SOM sources, illustrating the usefulness of fatty acid biomarkers in discriminating organic matter sources within lake environments. Although organic matter sources of sediments varied in spatial and temporal patterns, the strong correlation between terrestrial plant and total organic carbon (R² = 0.60, p < 0.05) indicates that terrestrial plants were the dominant source in lake sediments.     

Antimicrobial activity of medicinal plants and induction of defense related compounds in banana fruits cv. Robusta against crown rot pathogens

A total of 72 plant extracts were tested in vitro for their ability to inhibit the mycelial growth of Lasiodiplodia theobromae and Colletotrichum musae the causal agents of crown rot disease of banana. The results showed that the leaf extract of Zimmu (an interspecific hybrid of Allium cepa L. × Allium sativum L.) and tuber extract of Zehneria scabra recorded maximum inhibition of mycelial growth and spore germination of both the test pathogens. The dipping of banana fruits in Zimmu leaf extract at 25% conc. exhibited 100% inhibition of crown rot disease in cold storage (14 °C) up to 35 days and increased the shelf life to 64 days. However, at room storage (28 ± 2 °C), the same treatment exhibited 86% inhibition of crown rot disease up to 12 days. It was found that the treatment of banana fruits with Zimmu leaf extract did not alter the organoleptic properties of banana. The biochemical analysis of banana fruits treated with Zimmu leaf extract showed significant increase in phenylalanine ammonia-lyase (PAL), chitinase and β-1,3-glucanase activities and enhanced accumulation of phenolic compounds compared to other treatments. These findings suggest that the effect of Zimmu leaf extract on crown rot disease may be associated with the direct fungi toxic property against the test pathogens and elicitation of defense related compounds in banana fruits.     

Synthesis,anti-inflammatory activity and modeling studies of cycloartane-type terpenes derivatives isolated from Parthenium argentatum

The 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema model in mice determined the anti-inflammatory activities in vivo of argentatins A, B and D, the main cycloartenol-type triterpenes present in Parthenium argentatum. Our results showed that argentatin B (ED₅₀ = 1.5 × 10⁻⁴ mmol/ear) and argentatin A (ED₅₀ = 2.8 × 10⁻⁴ mmol/ear) were more potent anti-inflammatory agents than indomethacin (ED₅₀ = 4.5 × 10⁻⁴ mmol/ear), the reference drug. Based on these findings, we decided to evaluate 13 derivatives of argentatins A and B. All the derivatives showed anti-inflammatory activity in the TPA-induced edema model in mice. The most active compound was 25-nor-cycloart-3, 16-dione-17-en-24-oic acid, obtained from argentatin A (ED₅₀ = 1.4 × 10⁻⁴ mmol/ear). Argentatin B was assayed as inhibitor of COX-2 activity one of the key enzymes involved in the TPA assay. The results showed that argentatin B at 15 μM doses inhibited 77% COX-2 activity. Docking studies suggest that argentatin B interacts with Arg 120, a key residue for COX-2 activity.     

Reduced creatine kinase as a central and peripheral biomarker in Huntington's disease

A major goal of current clinical research in Huntington's disease (HD) has been to identify preclinical and manifest disease biomarkers, as these may improve both diagnosis and the power for therapeutic trials. Although the underlying biochemical alterations and the mechanisms of neuronal degeneration remain unknown, energy metabolism defects in HD have been chronicled for many years. We report that the brain isoenzyme of creatine kinase (CK-BB), an enzyme important in buffering energy stores, was significantly reduced in presymptomatic and manifest disease in brain and blood buffy coat specimens in HD mice and HD patients. Brain CK-BB levels were significantly reduced in R6/2 mice by ～ 18% to ～ 68% from 21 to 91 days of age, while blood CK-BB levels were decreased by ～ 14% to ～ 44% during the same disease duration. Similar findings in CK-BB levels were observed in the 140 CAG mice from 4 to 12 months of age, but not at the earliest time point, 2 months of age. Consistent with the HD mice, there was a grade-dependent loss of brain CK-BB that worsened with disease severity in HD patients from ～ 28% to ～ 63%, as compared to non-diseased control patients. In addition, CK-BB blood buffy coat levels were significantly reduced in both premanifest and symptomatic HD patients by ～ 23% and ～ 39%, respectively. The correlation of CK-BB as a disease biomarker in both CNS and peripheral tissues from HD mice and HD patients may provide a powerful means to assess disease progression and to predict the potential magnitude of therapeutic benefit in this disorder.     

Cellular cholesterol accumulation modulates high fat high sucrose (HFHS) diet-induced ER stress and hepatic inflammasome activation in the development of non-alcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH), is the form of non-alcoholic fatty liver disease posing risk to progress into serious long term complications. Human and pre-clinical models implicate cellular cholesterol dysregulation playing important role in its development. Mouse model studies suggest synergism between dietary cholesterol and fat in contributing to NASH but the mechanisms remain poorly understood. Our laboratory previously reported the primary importance of hepatic endoplasmic reticulum cholesterol (ER-Chol) in regulating hepatic ER stress by comparing the responses of wild type, Ldlr −/− xLcat +/+ and Ldlr −/− xLcat −/− mice, to a 2% high cholesterol diet (HCD). Here we further investigated the roles of ER-Chol and ER stress in HFHS diet-induced NASH using the same strains. With HFHS diet feeding, both WT and Ldlr −/− xLcat +/+ accumulate ER-Chol in association with ER stress and inflammasome activation but the Ldlr −/− xLcat −/− mice are protected. By contrast, all three strains accumulate cholesterol crystal, in correlation with ER-Chol, albeit less so in Ldlr −/− xLcat −/− mice. By comparison, HCD feeding per se (i) is sufficient to promote steatosis and activate inflammasomes, and (ii) results in dramatic accumulation of cholesterol crystal which is linked to inflammasome activation in Ldlr −/− xLcat −/− mice, independent of ER-Chol. Our data suggest that both dietary fat and cholesterol each independently promote steatosis, cholesterol crystal accumulation and inflammasome activation through distinct but complementary pathways. In vitro studies using palmitate-induced hepatic steatosis in HepG2 cells confirm the key roles by cellular cholesterol in the induction of steatosis and inflammasome activations. These novel findings provide opportunities for exploring a cellular cholesterol-focused strategy for treatment of NASH.     

Endarterectomy patients with elevated levels of circulating IL-16 have fewer cardiovascular events during follow-up

Background and purposeIncreased interleukin 16 (IL-16) levels in carotid plaques have been associated with reduced incidence of cardiovascular (CV) events during follow-up in patients who underwent carotid endarterectomy (CEA). In the present study we aimed to determine whether high circulating levels of IL-16 also are associated with a decreased risk of CV events after CEA.MethodsPatients, who had their carotid plaques surgically removed (n = 473), were followed for a mean follow-up time of 3.1 years. Plasma levels of IL-16 the day before surgery were analyzed by proximity extension assay (PEA) and associated with the occurrence of CV events during follow-up (n = 98).ResultsHigh levels of circulating IL-16 were independently associated with a decreased risk of CV events when comparing the highest versus the lowest IL-16 tertile (hazard ratio [HR] 0.47; 95% CI 0.27–0.81; P = 0.007), as well as with CV deaths (HR 0.25; 95% CI 0.09–0.70; P = 0.008).ConclusionThese present findings indicate an association between IL-16 and less clinical complications of atherosclerosis in a population with known advanced carotid disease.     

Study of the interactions between the key spore coat morphogenetic proteins CotE and SpoVID

The capability of Bacillus subtilis spores to withstand extreme environmental conditions is thought to be conferred especially by their outermost proteinaceous protective layer, called the spore coat. Of the over 70 proteins that form the spore coat, only a small subset of them affect its morphogenesis, they are referred to as morphogenetic proteins. In this study we investigated the interaction between two spore coat morphogenetic proteins SpoVID and CotE. SpoVID is involved in the process of spore surface encirclement by individual coat proteins, these include CotE, which controls the assembly of the outer coat layer. Both proteins were proposed to be recruited to a common protein scaffold, but their direct association has not been previously shown. Here we studied the interactions between CotE and SpoVID in vitro for the first time by using molecule recognition force spectroscopy, which allows the detection of piconewton forces between conjugated biological pairs and also facilitates the investigation of dynamic processes. The most probable CotE–CotE unbinding force was 49.4 ± 0.1 pN at a loading rate of 3.16 × 10³ pN/s while that of SpoVID–CotE was 26.5 ± 0.6 pN at a loading rate of 7.8 × 10² pN/s. We further analyzed the interactions with the bacterial two hybrid system and pull-down experiments, which also indicate that SpoVID interacts directly with CotE. In combination with the previously identified direct contacts among SpoIVA, SpoVID and SafA, our data imply that the physical association of key morphogenetic proteins forms a basic skeleton where other coat proteins could be attached.     

Evidence that pigeons represent both time and number on a logarithmic scale

Pigeons were presented with trials that always began with presentation of a houselight that lasted for 1–16 s. Red and green side keys were presented immediately after the houselight went off. A peck on the red key was reinforced if the houselight duration was 8 s or shorter, and a peck on the green key was reinforced if the houselight duration was 9 s or longer. Plots of asymptotic performance as a function of houselight duration showed bow-shaped curves with higher accuracy at the ends of the scale than in the middle. Training to bisect a scale containing houselight durations of 2–32 s yielded a performance curve that superimposed on the 1–16 s curve. Both curves showed two important asymmetries around the midpoint: pigeons were more accurate at 9 and 10 s than at 7 and 8 s but were more accurate at 1–4 s than at 13–16 s. These findings closely resembled those found in a similar study of number scale bisection [Roberts, W.A., 2005. How do pigeons represent numbers? Studies of number scale bisection. Behav. Process. 69, 33–43]. Theoretical predictions from associative and confusion models showed a good match to the obtained data if it was assumed that time and number scales were logarithmic and that generalization or confusion curves were constant but not if it was assumed that scales were linear and that generalization or confusion curves were scalar.     

Genetic association of IL2RA,IL17RA,IL23R,and IL31RA single nucleotide polymorphisms with alopecia areata

The signalling of cytokine receptors plays a crucial role in regulating tolerance and immunity. Impaired immunological processes result in autoimmune inflammation that target the hair follicles, causing many hair disorders, mainly alopecia areata (AA). Therefore, polymorphisms in cytokine receptor genes are suggested to have a significant impact on the pathogenesis of AA, a disease with a multifactorial basis and uncertain etiology. In the present study, 152 AA patients of the Jordanian population were investigated for their genetic susceptibility to develop AA compared to 150 control subjects. Genomic DNA extraction and genotyping had conducted for IL17RA (rs879575, rs2229151, and rs4819554), IL2RA (rs3118470), IL23R (rs10889677), and IL31RA (rs161704) using the Sequenom MassARRAY® system. The allele frequency of IL17RA rs879575 is significantly higher in patients, while no statistical differences were found for IL2RA, IL23R, and IL31RA SNPs. Also, the recessive model of IL31RA rs161704 showing that AA genotype is significantly associated with AA development. To date, there is no published data regarding the association between AA and the selected genetic variants in our population. However, this study's findings assert that SNPs of IL17RA and IL31RA are linked to AA susceptibility in Jordanian patients.     

A habitat quality indicator for common birds in Europe based on species distribution models

The EU 2020 Biodiversity Strategy requires the gathering of information on biodiversity to aid in monitoring progress towards its main targets. Common species are good proxies for the diversity and integrity of ecosystems, since they are key elements of the biomass, structure, functioning of ecosystems, and therefore of the supply of ecosystem services. In this sense, we aimed to develop a spatially-explicit indicator of habitat quality (HQI) at European level based on the species included in the European Common Bird Index, also grouped into their major habitat types (farmland and forest). Using species occurrences from the European Breeding Birds Atlas (at 50 km × 50 km) and the maximum entropy algorithm, we derived species distribution maps using refined occurrence data based on species ecology. This allowed us to cope with the limitations arising from modelling common and widespread species, obtaining habitat suitability maps for each species at finer spatial resolution (10 km × 10 km grid), which provided higher model accuracy. Analysis of the spatial patterns of local and relative species richness (defined as the ratio between species richness in a given location and the average richness in the regional context) for the common birds analysed demonstrated that the development of a HQI based on species richness needs to account for the regional species pool in order to make objective comparisons between regions. In this way, we proved that relative species richness compensated for the bias caused by the inherent heterogeneous patterns of the species distributions that was yielding larger local species richness in areas where most of the target species have the core of their distribution range. The method presented in this study provides a robust and innovative indicator of habitat quality which can be used to make comparisons between regions at the European scale, and therefore potentially applied to measure progress towards the EU Biodiversity Strategy targets. Finally, since species distribution models are based on breeding birds, the HQI can be also interpreted as a measure of the capacity of ecosystems to provide and maintain nursery/reproductive habitats for terrestrial species, a key maintenance and regulation ecosystem service.     

Juvenile neuronal ceroid lipofuscinosis and education

Juvenile neuronal ceroid lipofuscinosis (JNCL) is characterized by severe visual impairment with onset around age 4–8 years, and a developmental course that includes blindness, epilepsy, speech problems, dementia, motor coordination problems, and emotional reactions. There is presently no cure and the disease leads to premature death. There have been few studies of non-medical intervention for individuals with JNCL, probably because of the negative prognosis. The present chapter discusses the education of children and adolescents with JNCL on the basis of current knowledge about the variation in perceptual, cognitive and language abilities through the course of the disease, and the possibilities that exist for supporting coping and learning within and outside the classroom. Adapted and special needs education may contribute significantly to improved learning conditions, better maintenance of skills and less frustration for individuals with JNCL. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.     

How does the reliability of a model affect children's choice to learn socially or individually?

The effect of model reliability on children's choices to learn socially versus individually is pertinent to theories addressing cultural evolution and theories of selective trust. Here the effect of a reliable versus unreliable model on children's preferences to learn socially or individually was examined, as well as their subsequent imitation on a puzzle box task. Experiment One (N = 156) found children were more likely to ask to learn socially when presented with a novel task, after witnessing an unreliable rather than a reliable model. Experiment Two (N = 40) found children select a new unknown model, over the previously unreliable model, suggesting a preference to learn socially was created, although not specifically from the unreliable model. Experiment Three (N = 48) replicated children's learning preference in Experiment One with a new task, and showed children's attention is drawn towards other sources of social information (another adult model) when viewing an unreliable model, and also found a reliable model caused more fidelity of imitation. Together these results suggest that model unreliability causes greater social learning requests and attention to other, even novel, models when they are available. These findings evidence human children's strong propensity to learn socially compared with non-human animals; and suggest there is a more complicated relationship between learning preference, model reliability and selective trust than has been captured in previous research.     

Selenium status in elderly: Relation to cognitive decline

Studies show that decreased antioxidant system is related to cognitive decline. Thus we aimed to measure selenium (Se) status in Alzheimer's disease (AD) and mild cognitive impairment (MCI) elderly and compared them with a control group (CG). 27 AD, 17 MCI and 28 control elderly were evaluated. Se concentration was determined in plasma and erythrocyte by using hydride generation atomic absorption spectroscopy. Erythrocyte Se concentration in AD group was lower than CG (43.73 ± 23.02 μg/L and 79.15 ± 46.37 μg/L; p = 0.001), but not statistically different from MCI group (63.97 ± 18.26 μg/L; p = 0.156). AD group exhibited the lowest plasma Se level (34.49 ± 19.94 μg/L) when compared to MCI (61.36 ± 16.08 μg/L; p = 0.000) and to CG (50.99 ± 21.06 μg/L; p = 0.010). It is observed that erythrocyte Se decreases as cognition function does. Since erythrocyte reflects longer-term nutritional status, the data point to the importance of the relation between Se exposure and cognitive function. Our findings suggest that the deficiency of Se may contribute to cognitive decline among aging people.     

Selective inhibition of monoamine oxidase A by purpurin,an anthraquinone

Monoamine oxidase (MAO) catalyzes the oxidation of monoamines that act as neurotransmitters. During a target-based screening of natural products using two isoforms of recombinant human MAO-A and MAO-B, purpurin (an anthraquinone derivative) was found to potently and selectively inhibit MAO-A, with an IC₅₀ value of 2.50 μM, and not to inhibit MAO-B. Alizarin (also an anthraquinone) inhibited MAO-A less potently with an IC₅₀ value of 30.1 μM. Furthermore, purpurin was a reversible and competitive inhibitor of MAO-A with a K_i value of 0.422 μM. A comparison of their chemical structures suggested the 4-hydroxy group of purpurin might play an important role in its inhibition of MAO-A. Molecular docking simulation showed that the binding affinity of purpurin for MAO-A (?40.0 kcal/mol) was higher than its affinity for MAO-B (?33.9 kcal/mol), and that Ile 207 and Gly 443 of MAO-A were key residues for hydrogen bonding with purpurin. The findings of this study suggest purpurin is a potent, selective, reversible inhibitor of MAO-A, and that it be considered a new potential lead compound for development of novel reversible inhibitors of MAO-A (RIMAs).