Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): III. Emotional dysfunction superspectrum

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a quantitative nosological system that addresses shortcomings of traditional mental disorder diagnoses, including arbitrary boundaries between psychopathology and normality, frequent disorder co‐occurrence, substantial heterogeneity within disorders, and diagnostic unreliability over time and across clinicians. This paper reviews evidence on the validity and utility of the internalizing and somatoform spectra of HiTOP, which together provide support for an emotional dysfunction superspectrum. These spectra are composed of homogeneous symptom and maladaptive trait dimensions currently subsumed within multiple diagnostic classes, including depressive, anxiety, trauma‐related, eating, bipolar, and somatic symptom disorders, as well as sexual dysfunction and aspects of personality disorders. Dimensions falling within the emotional dysfunction superspectrum are broadly linked to individual differences in negative affect/neuroticism. Extensive evidence establishes that dimensions falling within the superspectrum share genetic diatheses, environmental risk factors, cognitive and affective difficulties, neural substrates and biomarkers, childhood temperamental antecedents, and treatment response. The structure of these validators mirrors the quantitative structure of the superspectrum, with some correlates more specific to internalizing or somatoform conditions, and others common to both, thereby underlining the hierarchical structure of the domain. Compared to traditional diagnoses, the internalizing and somatoform spectra demonstrated substantially improved utility: greater reliability, larger explanatory and predictive power, and greater clinical applicability. Validated measures are currently available to implement the HiTOP system in practice, which can make diagnostic classification more useful, both in research and in the clinic.     

The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials,and of some current trends aiming to de-risk trial programmes of novel agents

Despite considerable progress in pharmacotherapy over the past seven decades, many mental disorders remain insufficiently treated. This situation is in part due to the limited knowledge of the pathophysiology of these disorders and the lack of biological markers to stratify and individualize patient selection, but also to a still restricted number of mechanisms of action being targeted in monotherapy or combination/augmentation treatment, as well as to a variety of challenges threatening the successful development and testing of new drugs. In this paper, we first provide an overview of the most promising drugs with innovative mechanisms of action that are undergoing phase 2 or 3 testing for schizophrenia, bipolar disorder, major depressive disorder, anxiety and trauma-related disorders, substance use disorders, and dementia. Promising repurposing of established medications for new psychiatric indications, as well as variations in the modulation of dopamine, noradrenaline and serotonin receptor functioning, are also considered. We then critically discuss the clinical trial parameters that need to be considered in depth when developing and testing new pharmacological agents for the treatment of mental disorders. Hurdles and perils threatening success of new drug development and testing include inadequacy and imprecision of inclusion/exclusion criteria and ratings, sub-optimally suited clinical trial participants, multiple factors contributing to a large/increasing placebo effect, and problems with statistical analyses. This information should be considered in order to de-risk trial programmes of novel agents or known agents for novel psychiatric indications, increasing their chances of success.     

Genomic constitution and taxonomy of the Chinese hexaploids Elymus cylindricus and E. breviaristatus (Poaceae: Triticeae)

Elymus cylindricus (2n = 6x = 42) and E. breviaristatus (2n = 6x = 42) are distributed in grasslands and deserts of northern and north‐western China. Their genomic constitution and taxonomic status are unclear. Elymus cylindricus was crossed with E. wawawaiensis J.R.Carlson & Barkworth ( StH ), Roegneria grandis Keng ( StY ) and Campeiostachys dahurica (Turcz. ex Griseb.) B.R.Baum, J.L. Y ang & C. Y en var. dahurica ( StYH ). Meiotic pairing in the hybrids E. cylindricus × E. wawawaiensis ( StH ), E. cylindricus × R. grandis ( StY ) and E. cylindricus × C. dahurica var. dahurica ( StYH ) showed on average 10.00, 11.30 and 20.92 bivalents per cell, respectively. Elymus breviaristatus was crossed with C. dahurica var. dahurica ( StYH ) and E. cylindricus. Chromosome pairing in the hybrids of E. breviaristatus × C. dahurica var. dahurica and E. breviaristatus × E. cylindricus showed on average 19.60 and 19.27 bivalents, respectively. Genomic in situ hybridization (GI SH ) revealed the presence of St , Y and H genomes in E. cylindricus and E. breviaristatus. An intergenomic rearrangement was observed in E. cylindricus using GI SH . Meiotic pairing data and GI SH indicated that both E. cylindricus and E. breviaristatus are allohexaploids containing the StYH genomes. Elymus cylindricus and E. breviaristatus should be treated as Campeiostachys dahurica var. cylindrica and Campeiostachys breviaristata, respectively.     

In vivo expression of human ATP:cob(I)alamin adenosyltransferase (ATR) using recombinant adeno-associated virus (rAAV) serotypes 2 and 8

BACKGROUND: Methylmalonic aciduria (MMA) is an autosomal recessive disease with symptoms that include ketoacidosis, lethargy, recurrent vomiting, dehydration, respiratory distress, muscular hypotonia and death due to methylmalonic acid levels that are up to 1000-fold greater than normal. CblB MMA, a subset of the mutations leading to MMA, is caused by a deficiency in the enzyme cob(I)alamin adenosyltransferase (ATR). No animal model currently exists for this disease. ATR functions within the mitochondria matrix in the final conversion of cobalamin into coenzyme B(12), adenosylcobalamin (AdoCbl). AdoCbl is a required coenzyme for the mitochondrial enzyme methylmalonyl-CoA mutase (MCM). METHODS: The human ATR cDNA was cloned into a recombinant adeno-associated virus (rAAV) vector and packaged into AAV 2 or 8 capsids and delivered by portal vein injection to C57/Bl6 mice at a dose of 1 x 10(10) and 1 x 10(11) particles. Eight weeks post-injection RNA, genomic DNA and protein were then extracted and analyzed. RESULTS: Using primer pairs specific to the cytomegalovirus (CMV) enhancer/chicken beta-actin (CBAT) promoter within the rAAV vectors, genome copy numbers were found to be 0.03, 2.03 and 0.10 per cell in liver for the rAAV8 low dose, rAAV8 high dose and rAAV2 high dose, respectively. Western blotting performed on mitochondrial protein extracts demonstrated protein levels were comparable to control levels in the rAAV8 low dose and rAAV2 high dose animals and 3- to 5-fold higher than control levels were observed in high dose animals. Immunostaining demonstrated enhanced transduction efficiency of hepatocytes to over 40% in the rAAV8 high dose animals, compared to 9% and 5% transduction in rAAV2 high dose and rAAV8 low dose animals, respectively. CONCLUSIONS: These data demonstrate the feasibility of efficient ATR gene transfer to the liver as a prelude to future gene therapy experiments.     

Prevalence and trends of common mental disorders from 2007-2009 to 2019-2022: results from the Netherlands Mental Health Survey and Incidence Studies (NEMESIS), including comparison of prevalence rates before vs. during the COVID-19 pandemic

Up-to-date information on the prevalence and trends of common mental disorders is relevant to health care policy and planning, owing to the high burden associated with these disorders. In the first wave of the third Netherlands Mental Health Survey and Incidence Study (NEMESIS-3), a nationally representative sample was interviewed face-to-face from November 2019 to March 2022 (6,194 subjects; 1,576 interviewed before and 4,618 during the COVID-19 pandemic; age range: 18-75 years). A slightly modified version of the Composite International Diagnostic Interview 3.0 was used to assess DSM-IV and DSM-5 diagnoses. Trends in 12-month prevalence rates of DSM-IV mental disorders were examined by comparing these rates between NEMESIS-3 and NEMESIS-2 (6,646 subjects; age range: 18-64 years; interviewed from November 2007 to July 2009). Lifetime DSM-5 prevalence estimates in NEMESIS-3 were 28.6% for anxiety disorders, 27.6% for mood disorders, 16.7% for substance use disorders, and 3.6% for attention-deficit/hyperactivity disorder. Over the last 12 months, prevalence rates were 15.2%, 9.8%, 7.1%, and 3.2%, respectively. No differences in 12-month prevalence rates before vs. during the COVID-19 pandemic were found (26.7% pre-pandemic vs. 25.7% during the pandemic), even after controlling for differences in socio-demographic characteristics of the respondents interviewed in these two periods. This was the case for all four disorder categories. From 2007-2009 to 2019-2022, the 12-month prevalence rate of any DSM-IV disorder significantly increased from 17.4% to 26.1%. A stronger increase in prevalence was found for students, younger adults (18-34 years) and city dwellers. These data suggest that the prevalence of mental disorders has increased in the past decade, but this is not explained by the COVID-19 pandemic. The already high mental disorder risk of young adults has particularly further increased in recent years.     

Taxonomy of the New Zealand genus Eulimnia,and biology and immature stages of E. philpotti (Diptera: Sciomyzidae)

Abstract

The endemic New Zealand genus Eulimnia and its two species are redescribed. Data are presented on the life cycle of E. philpotti Tonnoir & Malloch, and the habitat, geographical distribution, phenology, and biological features of adults and immature stages are discussed. Adults are found in permanently wet marshes, where the larvae prey on fingernail clams (Bivalvia: Sphaeriidae) while completely submerged. Mature larvae form puparia among vegetation or debris above the water level. The immature stages of E. philpotti are described. The genus is placed in tribe Tetanocerini, and its taxonomic position is discussed.     

Biological destruction of CCl(4): I. Experimental design and data

A denitrifying consortium capable of transforming carbon tetrachloride (CCl(4)) was cultured from aquifer sediment from the U.S. Department of Energy's Hanford Site in southeastern Washington State. To understand the kinetics of the biological destruction of CCl(4) by these microbes, a set of experiments, the conditions of which were chosen according to a fractional factorial experimental design, were completed. This article reports on the experimental design along with the results for CCl(4), biomass, acetate, nitrate, and nitrite concentrations. These data indicate that growth is inhibited by high nitrite concentrations, whereas CCl(4) degradation is slowed by the presence of nitrate and/or nitrite. (c) 1994 John Wiley & Sons, Inc.     

Taxonomy and phylogeny of two poorly studied genera of marine oligotrich ciliates including descriptions of two new species: Cyrtostrombidium paraboreale sp. n. and Apostrombidium orientale sp. n. (Ciliophora: Spirotrichea)

Although it is widely recognized that oligotrich ciliates are the dominant constituent of microzooplankton communities and perform key functions in energy flow and material cycling in marine microbial food webs, knowledge of their diversity is scant. In the present study, we investigate the oligotrich genera, Cyrtostrombidium and Apostrombidium, with emphasis on their morphology and evolutionary relationships. Three isolates were collected from coastal waters of northern and southern China including two new species, viz., Cyrtostrombidium paraboreale sp. n., Apostrombidium orientale sp. n., and Apostrombidium pseudokielum Xu et al., 2009. Cyrtostrombidium paraboreale sp. n. is characterized by possessing 64–98 cytopharyngeal rods and two macronuclear nodules. Apostrombidium orientale sp. n. is characterized by its somatic kinety consisting of five fragments including a horizontally orientated subterminal fragment and possessing conspicuously long dorsal cilia. Apostrombidium pseudokielum is redescribed based on the new population and a re-examination of the type material. Phylogenetic analyses were performed for the subclass Oligotrichia, incorporating SSU rRNA gene sequences of the three species investigated here. The results indicate that the genus Cyrtostrombidium is monophyletic with C. paraboreale sp. n. occupying the basal position. The genus Apostrombidium is not monophyletic as Varistrombidium kielum is nested within it.     

The production of hydroxyl radical from copper(I) complex systems of bleomycin and tallysomycin: comparison with copper(II) and iron(II) systems.

In contrast with BLM(or TALM)-Cu(II) complex system, Cu(I)-O₂ system of BLM(or TALM) as well as the corresponding Fe(II) system evidently produces reactive oxygen radicals as detected by ESR spin trapping. The sulfhydryl compound strongly prevented the generation of hydroxyl radical in BLM(or TALM)-Cu(I)-O₂ system. TALM forms metal complexes similar to BLM. The action mechanism of BLM and TALM has been proposed to be substantially same.     

Lehr's fields of campaniform sensilla in beetles (Coleoptera): Functional morphology. I. General part and allometry

In this first of three articles we show the construction of the articular part of the elytron, the root. The root bears a conspicuous field of campaniform sensilla. This field was studied using light and scanning electron microscopes. The diversity of shape of the field among beetles, types of orientation of elongated sensilla within the field, individual variability of their number among conspecifics are demonstrated. Elongated sensilla point to the junction of the elytron with the second axillary plate. Presumably, they monitor twist movement in this junction, which is possible if the elytron is open. The goal of the whole project is to reveal the effect of both structure and function of the hind wings and elytra on the morphology of this mechanosensory field. Our data on allometric relationships between the animal size and quantitative characteristics of the field in normally flying beetles provide an important background for further functional analysis of this sensory organ.We selected 14 series of several species belonging to the same taxon but differing in size from big to small. It is revealed that the area of the sensory field is directly proportional to the elytral area, whereas the number of sensilla is proportional to the square root of the elytral area. Despite the great range in the elytral area (1500 times) in series of selected species the area of an external pit or cap of a single sensillum varies only 25-fold. The density of sensilla per unit area of the sensory field increases with decrease of the elytral area.     

Taxonomy of the European Hydra (Gnidaria: Hydrozoa): a re-examination of its history with emphasis on the species H. vulgaris Pallas, H. attenuata Pallas and H. circumcincta Schulze

The name Hydra attenuata Pallas is currently applied to the wrong animal. The common brown polyp, which is widely called H. attenuata, was described by Pallas (1766) as Hydra vulgaris. The name H. attenuata Pallas originally referred to an uncommon pale polyp, currently known as H. circumcincta Schulze. The history of this confusion is analysed here. The taxonomy of hydra was in disarray during the 18th and 19th centuries, and was clarified in 1917 with the monograph of Schulze. But Schulze misapplied the name for the common hydra, H. vulgaris, to an unusual form and thus was led to assign the name of a rare hydra, H. attenuata, to the common type. Schulze redescribed the rare, pale hydra that Pallas had named H. attenuata as H. circumcincta. The correct name of the common European brown, stalkless hydra is thus H. vulgaris Pallas, 1766. The name H. attenuata has priority for the uncommon pale hydra, but because of disuse of this application of the name, the pale hydra should be recognized by the current, generally accepted binominal H. circumcincta Schulze, 1914.     

Genetic variability inCebus appella paraguayanus: Biochemical analysis of seven loci and variation in Glyoxalase I (E.C.4.4.1.5)

An analysis of seven loci inCebus apella paraguayanus showed that Glyoxalase I was polymorphic due the appearance of two alleles (GLO*2 andGLO*3) with frequencies of 0.955 and 0.045, respectively. Of the two alleles,GLO*2 was electrophoretically similar to the most common allele found in the human andAotus. These results confirmed our previous findings in the same population sample showing that this subspecies has a very low genetic variation among New World primates.     

Structure and function of the spermathecal complex in the phlebotomine sandflyPhlebotomus papatasi Scopoli (Diptera: Psychodidae): I. Ultrastructure and histology

Females of phlebotomine sandflies (Diptera: Psychodidae) possess highly variable spermathecae that present several important taxonomic characters. The cause of this diversity remains a neglected field of sandfly biology, but may possibly be due to female post-mating sexual selection. To understand this diversity, a detailed study of the structure and function of the spermathecal complex in at least one of the species was a prerequisite. Using scanning and transmission electron microscopy, described here is ultrastructure of the spermathecal complex in the sand fly,Phlebotomus papatasi Scopoli. The spermathecal complexes are paired; each consists of a long spermathecal duct, a cylindrical spermathecal body, and a spherical spermathecal gland. Muscle fibres, nerves, tracheoles, and vascular sinuses connect the spermathecal body and duct through the epithelial layers. Spermathecal gland is formed by a typical insect epidermis and consisting of an epithelial layer of class-1 epidermal cells and elaborate glandular cells of class-3 epidermal cells, each having both receiving and conducting ductules (i.e. “end apparatus”) and a “cytological apodeme”, which is a newly described cell structure. The spermathecal body and duct are lined by class-1 epidermal cells and a cuticle, and are enveloped by a super-contracting visceral muscular system. The cuticle consists of rubber-like resilin, and its fibrillar arrangement and chemical nature are described. A well-developed neuromuscular junction exists between the spermathecal gland and the spermathecal body, which are connected to each other by a nerve and a muscle. The spermathecal complexes of the sandfly are compared with those of other insect species. The physiological role and possible evolutionary significance of the different parts of spermathecal complex in the sandfly are inferred from the morphology and behaviour. Post-mating sexual selection may be responsible for the structural uniqueness of the spermathecal complex in phlebotomine sandflies.     

Taxonomical significance of the leaf indument inDryopteris (Pteridophyta): I. Some North American,Macaronesian and European taxa

The leaf indument of a number of North American, Macaronesian and EuropeanDryopteris taxa is described. Trichome characters provide very useful taxonomical data for the study of species complexes and for tracing relationships among geographically isolated or separated taxa. The new combination,D. expansa var.alpina, is made. The present study sustains best theWagner D. semicristata relationship scheme.