Interspecies Recombination Has Driven the Macroevolution of Cassava Mosaic Begomoviruses.

Begomoviruses (family Geminiviridae, genus Begomovirus) significantly hamper crop production and threaten food security around the world. The frequent emergence of new begomovirus genotypes is facilitated by high mutation frequencies and the propensity to recombine and reassort. Homologous recombination has been especially implicated in the emergence of novel cassava mosaic begomovirus (CMB) genotypes, which cause cassava mosaic disease (CMD). Cassava (Manihot esculenta) is a staple food crop throughout Africa and an important industrial crop in Asia, two continents where production is severely constrained by CMD. The CMD species complex is comprised of 11 bipartite begomovirus species with ample distribution throughout Africa and the Indian subcontinent. While recombination is regarded as a frequent occurrence for CMBs, a revised, systematic assessment of recombination and its impact on CMB phylogeny is currently lacking. We assembled data sets of all publicly available, full-length DNA-A (n = 880) and DNA-B (n = 369) nucleotide sequences from the 11 recognized CMB species. Phylogenetic networks and complementary recombination detection methods revealed extensive recombination among the CMB sequences. Six out of the 11 species descended from unique interspecies recombination events. Estimates of recombination and mutation rates revealed that all species experience mutation more frequently than recombination, but measures of population divergence indicate that recombination is largely responsible for the genetic differences between species. Our results support that recombination has significantly impacted the CMB phylogeny and has driven speciation in the CMD species complex. IMPORTANCE Cassava mosaic disease (CMD) is a significant threat to cassava production throughout Africa and Asia. CMD is caused by a complex comprised of 11 recognized virus species exhibiting accelerated rates of evolution, driven by high frequencies of mutation and genetic exchange. Here, we present a systematic analysis of the contribution of genetic exchange to cassava mosaic virus species-level diversity. Most of these species emerged as a result of genetic exchange. This is the first study to report the significant impact of genetic exchange on speciation in a group of viruses.

5-HTT genotype and inertia of negative affect in adolescents and young adults from the general population.

The study aims to replicate the previous found association of 5-HTTLPR and inertia of negative affect in daily life of adolescents and young adults. Data of 877 adolescents (aged 14-21 years) of the Behavior and Mind Health (BeMIND) study (epidemiological cohort study, Dresden, Germany) were genotyped for 5-HTTLPR/rs25531, grouped into SS/SLG/SLA/LGLA/LGLG vs. LALA, and provided ratings on negative affect items, depression and anxiety (Patient-Reported Outcomes Measurement Information System) eight times a day over 4 days. Multilevel regression models did not reveal an association of 5-HTTLPR genotype and inertia of negative affect, nor associations with inertia of anxiety or depression. Inertia of negative affect seems not to be a psychological mechanism through which 5-HTTLPR acts on psychopathology.

Population diversity of cassava mosaic begomoviruses increases over the course of serial vegetative propagation.

Cassava mosaic disease (CMD) represents a serious threat to cassava, a major root crop for more than 300 million Africans. CMD is caused by single-stranded DNA begomoviruses that evolve rapidly, making it challenging to develop durable disease resistance. In addition to the evolutionary forces of mutation, recombination and reassortment, factors such as climate, agriculture practices and the presence of DNA satellites may impact viral diversity. To gain insight into the factors that alter and shape viral diversity in planta, we used high-throughput sequencing to characterize the accumulation of nucleotide diversity after inoculation of infectious clones corresponding to African cassava mosaic virus (ACMV) and East African cassava mosaic Cameroon virus (EACMCV) in the susceptible cassava landrace Kibandameno. We found that vegetative propagation had a significant effect on viral nucleotide diversity, while temperature and a satellite DNA did not have measurable impacts in our study. EACMCV diversity increased linearly with the number of vegetative propagation passages, while ACMV diversity increased for a time and then decreased in later passages. We observed a substitution bias toward C→T and G→A for mutations in the viral genomes consistent with field isolates. Non-coding regions excluding the promoter regions of genes showed the highest levels of nucleotide diversity for each genome component. Changes in the 5' intergenic region of DNA-A resembled the sequence of the cognate DNA-B sequence. The majority of nucleotide changes in coding regions were non-synonymous, most with predicted deleterious effects on protein structure, indicative of relaxed selection pressure over six vegetative passages. Overall, these results underscore the importance of knowing how cropping practices affect viral evolution and disease progression.

[Psychotherapy of anxiety disorders: state of the art]. / Psychotherapie der Angststörungen: State of the Art.

BACKGROUND: Alongside depression, anxiety disorders are the most frequent reason for consulting a psychotherapist. OBJECTIVE: This article describes the recent progress in understanding basic learning processes in anxiety treatment, the resulting therapeutic procedures, the current state of knowledge on the efficacy of the various psychotherapeutic procedures and on the moderators of the success of treatment. MATERIAL AND METHODS: The English and German language literature was reviewed and compiled, with an emphasis on the last 10 years. RESULTS: Cognitive-behavioral therapy (CBT) achieves the best and broadest level of evidence across all anxiety disorders. Initial studies have also provided emerging evidence for the efficacy of manualized short-term psychodynamic treatment. The most discussed mechanism of action is that of inhibitory learning. Augmentation strategies and personalized treatment approaches are gaining in relevance. CONCLUSION: Current models of inhibitory learning are rooted in basic research and foster a deeper understanding of the underlying neurobiological mechanisms. In order to optimize success of exposure treatment in vulnerable subgroups of patients, many procedural, device-based and pharmacological augmentation strategies are currently under investigation, whereby the latter are mostly still in the stage of (pre)clinical testing.

[Contrast medium-induced acute kidney injury-Consensus paper of the working group "Heart and Kidney" of the German Cardiac Society and the German Society of Nephrology]. / Kontrastmittelinduzierte akute Nierenschädigung ­ Konsensuspapier der Arbeitsgemeinschaft "Herz ­ Niere" der Deutschen Gesellschaft für Kardiologie ­ Herz- und Kreislaufforschung e. V. und der Deutschen Gesellschaft für Nephrologie e. V.

This consensus paper summarizes the expert consensus and recommendations of the working group "Heart and Kidney" of the German Cardiac Society (DGK) and the German Society of Nephrology (DGfN) on contrast medium-induced acute kidney injury. Potentially nephrotoxic contrast agents containing iodine are frequently used in interventional medicine and for computer tomography diagnostics. Acute kidney injury occurs in approximately 8-17% of patients exposed to contrast media. The risk factors and underlying pathophysiology are discussed and recommendations for the prophylaxis and treatment of contrast medium-induced acute nephropathy are presented.

Non-suicidal self-injury and its co-occurrence with suicidal behavior: An epidemiological-study among adolescents and young adults.

OBJECTIVE: Non-suicidal self-injury (NSSI) comprising thoughts and behaviors is common and often co-occurring with suicidal behavior like ideation, plan, and attempt. As limited data are available for adolescents and young adults, this study aims to present prevalence estimates for lifetime NSSI, its co-occurrence with suicidal behavior, conditional probabilities and their association with socio-demographic characteristics, severity characteristics of suicidal behavior, and health service utilization. METHOD: The epidemiological Behavior and Mind Health (BeMIND) study assessed in 2015/16 a random-community sample of N = 1180 aged 14-21 years from Dresden, Germany, regarding lifetime NSSI via self-administered questionnaire and suicidal behaviors via standardized interview. RESULTS: Any lifetime NSSI was reported by 19.3% (thoughts: 18.0%, behaviors: 13.6%) of the sample with higher prevalence in females (OR = 2.7, 95% CI 1.9-3.8, P < 0.001). Lifetime prevalence of co-occurring NSSI and suicidal behavior was 7.7%. Females had a 3.3- to 8.8-fold odds of co-occurrence than males. Among those with any NSSI, 39.6% endorsed suicidal behavior, and 66.3% of those with any suicidal behavior reported NSSI. 42.3% of those with any NSSI reported to have used mental healthcare services at any time during their life with higher rates in those with co-occurring suicidal behavior (62.3%). CONCLUSION: Non-suicidal self-injury and co-occurring suicidal behavior is common in adolescents and young adults-especially females. The limited utilization of mental healthcare services underpins the need for improving recognition of NSSI and suicidal behavior as well as the accessibility of mental healthcare services during adolescence and emerging adulthood.

Liebowitz Social Anxiety Scale (LSAS): Optimal cut points for remission and response in a German sample.

The Liebowitz Social Anxiety Scale (LSAS) is the most frequently used instrument to assess social anxiety disorder (SAD) in clinical research and practice. Both a self-reported (LSAS-SR) and a clinician-administered (LSAS-CA) version are available. The aim of the present study was to define optimal cut-off (OC) scores for remission and response to treatment for the LSAS in a German sample. Data of N = 311 patients with SAD were used who had completed psychotherapeutic treatment within a multicentre randomized controlled trial. Diagnosis of SAD and reduction in symptom severity according to the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, served as gold standard. OCs yielding the best balance between sensitivity and specificity were determined using receiver operating characteristics. The variability of the resulting OCs was estimated by nonparametric bootstrapping. Using diagnosis of SAD (present vs. absent) as a criterion, results for remission indicated cut-off values of 35 for the LSAS-SR and 30 for the LSAS-CA, with acceptable sensitivity (LSAS-SR: .83, LSAS-CA: .88) and specificity (LSAS-SR: .82, LSAS-CA: .87). For detection of response to treatment, assessed by a 1-point reduction in the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, rating, a reduction of 28% for the LSAS-SR and 29% for the LSAS-CA yielded the best balance between sensitivity (LSAS-SR: .75, LSAS-CA: .83) and specificity (LSAS-SR: .76, LSAS-CA: .80). To our knowledge, we are the first to define cut points for the LSAS in a German sample. Overall, the cut points for remission and response corroborate previously reported cut points, now building on a broader data basis.

Roles and programming of Arabidopsis ARGONAUTE proteins during Turnip mosaic virus infection.

In eukaryotes, ARGONAUTE proteins (AGOs) associate with microRNAs (miRNAs), short interfering RNAs (siRNAs), and other classes of small RNAs to regulate target RNA or target loci. Viral infection in plants induces a potent and highly specific antiviral RNA silencing response characterized by the formation of virus-derived siRNAs. Arabidopsis thaliana has ten AGO genes of which AGO1, AGO2, and AGO7 have been shown to play roles in antiviral defense. A genetic analysis was used to identify and characterize the roles of AGO proteins in antiviral defense against Turnip mosaic virus (TuMV) in Arabidopsis. AGO1, AGO2 and AGO10 promoted anti-TuMV defense in a modular way in various organs, with AGO2 providing a prominent antiviral role in leaves. AGO5, AGO7 and AGO10 had minor effects in leaves. AGO1 and AGO10 had overlapping antiviral functions in inflorescence tissues after systemic movement of the virus, although the roles of AGO1 and AGO10 accounted for only a minor amount of the overall antiviral activity. By combining AGO protein immunoprecipitation with high-throughput sequencing of associated small RNAs, AGO2, AGO10, and to a lesser extent AGO1 were shown to associate with siRNAs derived from silencing suppressor (HC-Pro)-deficient TuMV-AS9, but not with siRNAs derived from wild-type TuMV. Co-immunoprecipitation and small RNA sequencing revealed that viral siRNAs broadly associated with wild-type HC-Pro during TuMV infection. These results support the hypothesis that suppression of antiviral silencing during TuMV infection, at least in part, occurs through sequestration of virus-derived siRNAs away from antiviral AGO proteins by HC-Pro. These findings indicate that distinct AGO proteins function as antiviral modules, and provide a molecular explanation for the silencing suppressor activity of HC-Pro.

[Mental disorders in women: Natural course during premenstrual phases, peripartum period and perimenopause]. / Psychische Störungen in den reproduktiven Phasen der Frau: Häufigkeiten, Verlauf und Besonderheiten.

Epidemiological studies indicate sex-specific differences in prevalence rates and the natural course of mental disorders. Affective, anxiety, somatoform and eating disorders are more prevalent in women than men, whereas substance use disorders occur more commonly in men, and some disorders are equally distributed in both sexes (e. g. psychotic disorders). The aim of this review is to depict the natural course of mental disorders during the reproductive stages (premenstrual phases, peripartum period, perimenopause) in women, including also neuroendocrine features associated with the menstrual cycle, pregnancy, puerperium and perimenopause. Recommendations for sex-specific diagnostic and therapeutic procedures are provided.

[Salt restriction in people with hypertension and patients with cardiovascular disease : meaningfulness and extent]. / Kochsalzrestriktion bei Menschen mit Hypertonie und kardiovaskulären Patienten : Sinnhaftigkeit und Ausmaß.

UNLABELLED: The association between high salt (NaCl) intake and increased blood pressure has been demonstrated in a multitude of studies. Clear evidence for a blood pressure lowering effect of a reduction in dietary NaCl has also been reported. In contrast to the antihypertensive effect of NaCl reduction, from a clinical scientific perspective a positive effect on cardiovascular mortality has not been sufficiently demonstrated. Often the proven blood pressure lowering effect of reduced NaCl intake was extrapolated to an effect on the cardiovascular risk. This article describes the current data situation and discusses the effects of NaCl restriction in people with hypertension and patients with cardiovascular diseases in detail. IN SUMMARY: moderate restriction of NaCl to 6 g/day is recommended for patients with hypertension or cardiovascular comorbidities, intensive reduction to ≤3 g/day is not recommended and for patients with few comorbidities an NaCl intake of up to 10 g/day has no obvious disadvantages.

Prevalence of suicidal ideation in German psychotherapy outpatients: A large multicenter assessment.

BACKGROUND: Suicidal ideation is a major concern in clinical practice. Yet, little is known about prevalence rates of suicidal ideation in patients undergoing outpatient psychotherapeutic treatment. Therefore, the aim of the current study is to assess the prevalence of suicidal ideation in a large sample of psychotherapy outpatients in Germany. The data analyzed in this study is taken from the KODAP-project on the coordination of data collection and analysis at German university-based research and training outpatient clinics for psychotherapy. METHODS: A total of N = 10,357 adult outpatients (64.4 % female; age: M(SD) = 35.94 (13.54), range: 18-92 years of age) starting cognitive-behavioral therapy at one of 27 outpatient clinics in Germany were included in the current study. Prevalence of suicidal ideation was assessed with the Suicide Item (Item 9) of the Beck-Depression Inventory II. RESULTS: Suicidal ideation was reported by 36.7 % (n = 3795) of the participants. Borderline Personality Disorder, Posttraumatic Stress Disorder, and recurrent Major Depression were the diagnoses most strongly associated with the presence and severity of suicidal ideation. LIMITATION: Suicide ideation was assessed only with the respective item of the Beck Depression Inventory II. CONCLUSION: Suicidal ideation is very common among adult patients who start psychotherapy in Germany. A well-founded knowledge of risk assessment in suicidal patients and suicide-specific treatment options is therefore highly relevant.

MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.

Recently, pathogenic variants in the MLL2 gene were identified as the most common cause of Kabuki (Niikawa-Kuroki) syndrome (MIM#147920). To further elucidate the genotype-phenotype correlation, we studied a large cohort of 86 clinically defined patients with Kabuki syndrome (KS) for mutations in MLL2. All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL2-Kabuki score 0-10). Sequencing of the full coding region and intron-exon boundaries of MLL2 identified a total of 45 likely pathogenic mutations (52%): 31 nonsense, 10 missense and four splice-site mutations, 34 of which were novel. In five additional patients, novel, i.e. non-dbSNP132 variants of clinically unknown relevance, were identified. Patients with likely pathogenic nonsense or missense MLL2 mutations were usually more severely affected (median 'MLL2-Kabuki score' of 6) as compared to the patients without MLL2 mutations (median 'MLL2-Kabuki score' of 5), a significant difference (p < 0.0014). Several typical facial features such as large dysplastic ears, arched eyebrows with sparse lateral third, blue sclerae, a flat nasal tip with a broad nasal root, and a thin upper and a full lower lip were observed more often in mutation positive patients.

Limited role of recombination in the global diversification of begomovirus DNA-B proteins.

Approximately half of the characterized begomoviruses have bipartite genomes, but the second genomic segment, the DNA-B, is understudied relative to the DNA-A, which is homologous to the entire genome of monopartite begomoviruses. We examined the evolutionary history of the two proteins encoded by the DNA-B, the genes of which make up ∼60% of the DNA-B segment, from all bipartite begomovirus species. Our dataset of 131 movement protein (MP) and nuclear shuttle protein (NSP) sequences confirmed the deep split between Old World (OW) and New World (NW) species, and showed strong support for deep, congruent branches among the OW sequences of the MP and NSP. NW sequences were much less diverse and had poor phylogenetic resolution; over half of nodes in both the NSP and MP NW clades were supported by <50% bootstrap support. This poor resolution hampered our ability to detect incongruent phylogenies between the MP and NSP datasets, and we found no statistical evidence for recombination within our MP and NSP datasets. Finally, we quantified the sequence diversity between the NW and OW proteins, showing that the NW MP has particularly low diversity, suggesting it has been subject to different evolutionary pressures than the NW NSP.

A Transducing Bacteriophage Infecting Staphylococcus epidermidis Contributes to the Expansion of a Novel Siphovirus Genus and Implies the Genus Is Inappropriate for Phage Therapy.

The effort to discover novel phages infecting Staphylococcus epidermidis contributes to both the development of phage therapy and the expansion of genome-based phage phylogeny. Here, we report the genome of an S. epidermidis-infecting phage, Lacachita, and compare its genome with those of five other phages with high sequence identity. These phages represent a novel siphovirus genus, which was recently reported in the literature. The published member of this group was favorably evaluated as a phage therapeutic agent, but Lacachita is capable of transducing antibiotic resistance and conferring phage resistance to transduced cells. Members of this genus may be maintained within their host as extrachromosomal plasmid prophages, through stable lysogeny or pseudolysogeny. Therefore, we conclude that Lacachita may be temperate and members of this novel genus are not suitable for phage therapy. IMPORTANCE This project describes the discovery of a culturable bacteriophage infecting Staphylococcus epidermidis that is a member of a rapidly growing novel siphovirus genus. A member of this genus was recently characterized and proposed for phage therapy, as there are few phages currently available to treat S. epidermidis infections. Our data contradict this, as we show Lacachita is capable of moving DNA from one bacterium to another, and it may be capable of maintaining itself in a plasmid-like state in infected cells. These phages' putative plasmid-like extrachromosomal state appears to be due to a simplified maintenance mechanism found in true plasmids of Staphylococcus and related hosts. We suggest Lacachita and other identified members of this novel genus are not suitable for phage therapy.

Cassava begomovirus species diversity changes during plant vegetative cycles.

Cassava is a root crop important for global food security and the third biggest source of calories on the African continent. Cassava production is threatened by Cassava mosaic disease (CMD), which is caused by a complex of single-stranded DNA viruses (family: Geminiviridae, genus: Begomovirus) that are transmitted by the sweet potato whitefly (Bemisia tabaci). Understanding the dynamics of different cassava mosaic begomovirus (CMB) species through time is important for contextualizing disease trends. Cassava plants with CMD symptoms were sampled in Lake Victoria and coastal regions of Kenya before transfer to a greenhouse setting and regular propagation. The field-collected and greenhouse samples were sequenced using Illumina short-read sequencing and analyzed on the Galaxy platform. In the field-collected samples, African cassava mosaic virus (ACMV), East African cassava mosaic virus (EACMV), East African cassava mosaic Kenya virus (EACMKV), and East African cassava mosaic virus-Uganda variant (EACMV-Ug) were detected in samples from the Lake Victoria region, while EACMV and East African mosaic Zanzibar virus (EACMZV) were found in the coastal region. Many of the field-collected samples had mixed infections of EACMV and another begomovirus. After 3 years of regrowth in the greenhouse, only EACMV-like viruses were detected in all samples. The results suggest that in these samples, EACMV becomes the dominant virus through vegetative propagation in a greenhouse. This differed from whitefly transmission results. Cassava plants were inoculated with ACMV and another EACMV-like virus, East African cassava mosaic Cameroon virus (EACMCV). Only ACMV was transmitted by whiteflies from these plants to recipient plants, as indicated by sequencing reads and copy number data. These results suggest that whitefly transmission and vegetative transmission lead to different outcomes for ACMV and EACMV-like viruses.

Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune bullous disorder which is characterized by blisters and erosions of the skin and mucous membranes. A frequently applied first-line therapy for PV consists of systemic corticosteroids (CS) combined with immunosuppressive agents. In refractory cases, novel therapeutic strategies such as immunoadsorption (IA) and the anti-CD20 antibody rituximab (Rtx) aim at directly interfering with pathogenic autoantibodies (auto-Abs). OBJECTIVES: To investigate the long-term efficacy of IA in combination with Rtx in patients with difficult-to-treat PV, we assessed the clinical response to treatment by monitoring the Autoimmune Bullous Skin Disorder Intensity Score, IgG auto-Abs against desmoglein 1 and 3 (Dsg1 and Dsg3) and the dose of systemic CS. METHODS: We retrospectively analysed clinical and serological parameters of 10 patients with difficult-to-treat PV who received IA at 4-week intervals, followed by Rtx either twice at 1000 mg or four times at 375mg m(-2) . During a 12-month follow-up period, CS were tapered according to the individual clinical status. RESULTS: Six months after the first IA treatment eight of 10 patients were in complete remission on therapy while one patient showed a partial response and one patient was unresponsive to the treatment. At 12 months, six of eight patients were in complete remission on therapy, one patient showed stable disease and one patient had relapsed. Overall, anti-Dsg3 IgG and anti-Dsg1 IgG auto-Abs correlated well with the clinical activity and systemic CS were tapered gradually. CONCLUSIONS: The present findings show that the combination of IA and Rtx induces rapid clinical remission and long-term control in difficult-to-treat pemphigus.

[Non-pharmacological and pharmacological treatment of arterial hypertension: current situation]. / Nichtmedikamentöse und medikamentöse Therapie bei arterieller Hypertonie: Aktueller Stand.

A permanent and successful treatment of high blood pressure is based on a combination of non-pharmacological treatment measures and pharmacological therapy. The most proven non-pharmacological measures are physical and sports activities, weight reduction, dietary adaption and reduction of salt intake as well as nicotine abstinence and moderate alcohol consumption. A blood pressure reducing effect of evidence grade A was demonstrated for these 4 pillars of non-pharmacological therapy in studies. For pharmacological treatment five main substance groups are available: thiazide diuretics, ACE inhibitors, AT1 blockers, calcium channel blockers and beta blockers. A very good blood pressure reducing effect with an advantageous side effect profile has been proven for all substances. The initial high blood pressure therapy can be carried out with monotherapy but therapy with several antihypertensives is often necessary for the very varied combination of compounds which are available in a meaningful combination and dosage of effective ingredients. For the treatment of comorbid hypertensive patients recommendations are available for an individualized pharmacological treatment corresponding to the specific cardiovascular risk and comorbidity. High blood pressure therapy must be continuously carried out over many years. For permanent success of the therapy good compliance is indispensible which can be encouraged by integration in the therapy and should be regularly controlled.

Complete Genome Sequences of Five Phietaviruses Infecting Staphylococcus aureus.

The annotated whole-genome sequences of five cultured phietaviruses infecting Staphylococcus aureus are presented. They are closely related to prophages that were previously sequenced as part of S. aureus genomes.

Early detection of plant virus infection using multispectral imaging and spatial-spectral machine learning.

Cassava brown streak disease (CBSD) is an emerging viral disease that can greatly reduce cassava productivity, while causing only mild aerial symptoms that develop late in infection. Early detection of CBSD enables better crop management and intervention. Current techniques require laboratory equipment and are labour intensive and often inaccurate. We have developed a handheld active multispectral imaging (A-MSI) device combined with machine learning for early detection of CBSD in real-time. The principal benefits of A-MSI over passive MSI and conventional camera systems are improved spectral signal-to-noise ratio and temporal repeatability. Information fusion techniques further combine spectral and spatial information to reliably identify features that distinguish healthy cassava from plants with CBSD as early as 28 days post inoculation on a susceptible and a tolerant cultivar. Application of the device has the potential to increase farmers' access to healthy planting materials and reduce losses due to CBSD in Africa. It can also be adapted for sensing other biotic and abiotic stresses in real-world situations where plants are exposed to multiple pest, pathogen and environmental stresses.