Long-term host–pathogen evolution of endogenous beta- and gammaretroviruses in mouse lemurs with little evidence of recent retroviral introgression

Madagascar’s flora and fauna have evolved in relative isolation since the island split from the African and Indian continents. When the last common ancestors of lemurs left Africa between 40 and 70 million years ago, they carried a subset of the viral diversity of the mainland population within them, which continued to evolve throughout the lemur radiation. Relative to other primate radiations, we know very little about the past or present viral diversity of lemurs, particularly mouse lemurs. Using high-throughput sequencing, we identified two gammaretroviruses and three betaretroviruses in the genomes of four species of wild mouse lemurs. The two gammaretroviruses and two betaretroviruses have not previously been described. One betaretrovirus was previously identified. All identified viruses are present in both Lorisiformes and Lemuriformes but absent from haplorrhine primates. The estimated ages of these viruses are consistent with the estimated divergence dates of the host lineages, suggesting they colonized the lemur genome after the Haplorrhine–Strepsirrhine split, but before the Lorisiformes–Lemuriformes split and before the colonization of Madagascar. The viral phylogenies connect multiple lineages of retroviruses from non-lemur and non-Madagascar-native species, suggesting substantial cross-species transmission occurred deep in the primate clade prior to its geographic dispersal. These phylogenies provide novel insights into known retroviral clades. They suggest that the origin of gammaretroviruses in rodents or bats may be premature and that the Jaagsiekte sheep virus clade may be older and more broadly distributed among mammals than previously thought

Global patterns of vascular plant alpha diversity

Global patterns of regional (gamma) plant diversity are relatively well known, but whether these patterns hold for local communities, and the dependence on spatial grain, remain controversial. Using data on 170,272 georeferenced local plant assemblages, we created global maps of alpha diversity (local species richness) for vascular plants at three different spatial grains, for forests and non-forests. We show that alpha diversity is consistently high across grains in some regions (for example, Andean-Amazonian foothills), but regional ‘scaling anomalies’ (deviations from the positive correlation) exist elsewhere, particularly in Eurasian temperate forests with disproportionally higher fine-grained richness and many African tropical forests with disproportionally higher coarse-grained richness. The influence of different climatic, topographic and biogeographical variables on alpha diversity also varies across grains. Our multi-grain maps return a nuanced understanding of vascular plant biodiversity patterns that complements classic maps of biodiversity hotspots and will improve predictions of global change effects on biodiversity

Intestinal barrier integrity in anorexia nervosa (a pilot study)

Objective There is no conclusive evidence for involvement of intestinal barrier alteration in the etiology of anorexia nervosa (AN). The aims of this pilot study were to identify serum markers of intestinal barrier integrity in patients with AN and to determine the relationships between those markers and body mass index (BMI), eating disorder symptoms, gastrointestinal complaints, and liver synthesis function (international normalized ratio [INR]). Method Twenty-five outpatients with AN prior to starting treatment and 28 healthy controls (HC) were assessed. BMI and serum markers of intestinal barrier integrity were measured, including zonulin family peptides (ZFP), lipopolysaccharide-binding protein (LBP), and intestinal fatty-acid-binding protein (i-FABP). Eating disorder symptoms and gastrointestinal complaints were evaluated via questionnaires. Results The serum ZFP concentration was significantly lower in patients with AN than in HC (44.2 [7.4] vs. 49.2 [5.6] ng/ml, mean [standard deviation], p = .008). LBP and i-FABP did not differ between the two groups. In patients with AN, serum ZFP was significantly predicted by BMI (β = 0.479, p = .009), age (β = 0.411, p = .020), and INR (β = −0.388, p = .028). No such associations were found for either gastrointestinal complaints or eating disorder symptoms. Discussion Abnormal levels of serum ZFP were observed in patients with AN. Further studies with other assessment methods are warranted to examine intestinal barrier function in AN.publishedVersio

A comprehensive evaluation of the activity and selectivity profile of ligands for RGD-binding integrins

Integrins, a diverse class of heterodimeric cell surface receptors, are key regulators of cell structure and behaviour, affecting cell morphology, proliferation, survival and differentiation. Consequently, mutations in specific integrins, or their deregulated expression, are associated with a variety of diseases. In the last decades, many integrin-specific ligands have been developed and used for modulation of integrin function in medical as well as biophysical studies. The IC50-values reported for these ligands strongly vary and are measured using different cell-based and cell-free systems. A systematic comparison of these values is of high importance for selecting the optimal ligands for given applications. In this study, we evaluate a wide range of ligands for their binding affinity towards the RGD-binding integrins avß3, avß5, avß6, avß8, a5ß1, aIIbß3, using homogenous ELISA-like solid phase binding assay.Postprint (published version

The study protocol of the Norwegian randomized controlled trial of electroconvulsive therapy in treatment resistant depression in bipolar disorder

<p>Abstract</p> <p>Background</p> <p>The treatment of depressive phases of bipolar disorder is challenging. The effects of the commonly used antidepressants in bipolar depression are questionable. Electroconvulsive therapy is generally considered to be the most effective treatment even if there are no randomized controlled trials of electroconvulsive therapy in bipolar depression. The safety of electroconvulsive therapy is well documented, but there are some controversies as to the cognitive side effects. The aim of this study is to compare the effects and side effects of electroconvulsive therapy to pharmacological treatment in treatment resistant bipolar depression. Cognitive changes and quality of life during the treatment will be assessed.</p> <p>Methods/Design</p> <p>A prospective, randomised controlled, multi-centre six- week acute treatment trial with seven clinical assessments. Follow up visit at 26 weeks or until remission (max 52 weeks). A neuropsychological test battery designed to be sensitive to changes in cognitive function will be used. Setting: Nine study centres across Norway, all acute psychiatric departments. Sample: n = 132 patients, aged 18 and over, who fulfil criteria for treatment resistant depression in bipolar disorder, Montgomery Åsberg Depression Rating Scale Score of at least 25 at baseline. Intervention: Intervention group: 3 sessions per week for up to 6 weeks, total up to 18 sessions. Control group: algorithm-based pharmacological treatment as usual.</p> <p>Discussion</p> <p>This study is the first randomized controlled trial that aims to investigate whether electroconvulsive therapy is better than pharmacological treatment as usual in treatment resistant bipolar depression. Possible long lasting cognitive side effects will be evaluated. The study is investigator initiated, without support from industry.</p> <p>Trial registration</p> <p>NCT00664976</p

Long-term host-pathogen evolution of endogenous beta- and gammaretroviruses in mouse lemurs with little evidence of recent retroviral introgression

Madagascar’s flora and fauna have evolved in relative isolation since the island split from the African and Indian continents. When the last common ancestors of lemurs left Africa between 40 and 70 million years ago, they carried a subset of the viral diversity of the mainland population within them, which continued to evolve throughout the lemur radiation. Relative to other primate radiations, we know very little about the past or present viral diversity of lemurs, particularly mouse lemurs. Using high-throughput sequencing, we identified two gammaretroviruses and three betaretroviruses in the genomes of four species of wild mouse lemurs. The two gammaretroviruses and two betaretroviruses have not previously been described. One betaretrovirus was previously identified. All identified viruses are present in both Lorisiformes and Lemuriformes but absent from haplorrhine primates. The estimated ages of these viruses are consistent with the estimated divergence dates of the host lineages, suggesting they colonized the lemur genome after the Haplorrhine–Strepsirrhine split, but before the Lorisiformes–Lemuriformes split and before the colonization of Madagascar. The viral phylogenies connect multiple lineages of retroviruses from non-lemur and non-Madagascar-native species, suggesting substantial cross-species transmission occurred deep in the primate clade prior to its geographic dispersal. These phylogenies provide novel insights into known retroviral clades. They suggest that the origin of gammaretroviruses in rodents or bats may be premature and that the Jaagsiekte sheep virus clade may be older and more broadly distributed among mammals than previously thought

The effect of electroconvulsive therapy (ECT) on serum tryptophan metabolites

Background: Prior studies suggest that activation of the tryptophan catabolism via the kynurenine pathway by proinflammatory cytokines may be involved in the pathophysiology of depression. Electroconvulsive therapy (ECT) is an effective treatment for major depression (MD) with immunomodulation as one of the proposed modes of action. Objective: The aim of this study was to investigate serum concentrations of tryptophan and kynurenine pathway metabolites in MD patients and healthy controls, and to explore the effect of ECT on components of the kynurenine pathway. Methods: The study included 27 moderately to severely depressed patients referred to ECT. Blood samples were collected prior to treatment and after the completed ECT-series. Baseline samples were also collected from 14 healthy, age- and sex-matched controls. Serum concentrations of tryptophan, kynurenine, 3-hydroxykynurenine (HK), kynurenic acid (KA), xanthurenic acid (XA), anthranilic acid (AA), 3-hydroxyanthranilic acid (HAA), quinolinic acid (QA), picolinic acid (Pic), pyridoxal 5′-phosphat (PLP), riboflavin, neopterin and cotinine were measured. Results: Patients with MD had lower levels of neuroprotective kynurenine-pathway metabolites (KA, XA and Pic) and lower metabolite ratios (KA/Kyn and KA/QA) reflecting reduced neuroprotection compared to controls. The concentration of the inflammatory marker neopterin was increased after ECT, along with Pic and the redox active and immunosuppressive metabolite HAA. Conclusion: In this pilot study, we found increased concentrations of inflammatory marker neopterin and putative neuroprotective kynurenine metabolites HAA and Pic in MD patients after ECT. Further research in larger cohorts is required to conclude whether ECT exerts its therapeutic effects via changes in the kynurenine pathway.publishedVersio

Neurocognitive profiles in treatment-resistant bipolar I and bipolar II disorder depression

Background The literature on the neuropsychological profiles in Bipolar disorder (BD) depression is sparse. The aims of the study were to assess the neurocognitive profiles in treatment-resistant, acutely admitted BD depression inpatients, to compare the neurocognitive functioning in patients with BD I and II, and to identify the demographic and clinical illness characteristics associated with cognitive functioning. Methods Acutely admitted BD I (n = 19) and BD II (n = 32) inpatients who fulfilled the DSM-IV-TR criteria for a major depressive episode were tested with the MATRICS Consensus Cognitive Battery (MCCB), the Wechsler Abbreviated Scale of Intelligence, the National Adult Reading Test, and a battery of clinical measures. Results Neurocognitive impairments were evident in the BD I and BD II depression inpatients within all MCCB domains. The numerical scores on all MCCB-measures were lower in the BD I group than in the BD II group, with a significant difference on one of the measures, category fluency. 68.4% of the BD I patients had clinically significant impairment (>1.5 SD below normal mean) in two or more domains compared to 37.5% of the BD II patients (p = 0.045). A significant reduction in IQ from the premorbid to the current level was seen in BD I but not BD II patients. Higher age was associated with greater neurocognitive deficits compared to age-adjusted published norms. Conclusions A high proportion of patients with therapy-resistant BD I or II depression exhibited global neurocognitive impairments with clinically significant severity. The cognitive impairments were more common in BD I compared to BD II patients, particularly processing speed. These findings suggest that clinicians should be aware of the severe neurocognitive dysfunction in treatment-resistant bipolar depression, particularly in BD I.publishedVersio

A new species of Schoutedenichia Jadin & Vercammen-Grandjean, 1954 from Madagascar and a re-description of S. dutoiti (Radford, 1948) from South Africa (Acariformes: Trombiculidae)

A new chigger mite species, Schoutedenichia microcebi n. sp. is described from the grey mouse lemur Microcebus murinus (J.F. Miller) from Madagascar. The new species is closely related to S. dutoiti (Radford, 1948), a species described from a single specimen collected on a rodent in South Africa. Examination of the holotype and new material on S. dutoiti from South Africa enabled us to re-describe this species and provide new data on its hosts and geographical distribution