Exploratory behaviour in NO-dependent cyclase mutants of Drosophila shows defects in coincident neuronal signalling

<p>Abstract</p> <p>Background</p> <p><it>Drosophila </it>flies explore the environment very efficiently in order to colonize it. They explore collectively, not individually, so that when a few land on a food spot, they attract the others by signs. This behaviour leads to aggregation of individuals and optimizes the screening of mates and egg-laying on the most favourable food spots.</p> <p>Results</p> <p>Flies perform cycles of exploration/aggregation depending on the resources of the environment. This behavioural ecology constitutes an excellent model for analyzing simultaneous processing of neurosensory information. We reasoned that the decision of flies to land somewhere in order to achieve aggregation is based on simultaneous integration of signals (visual, olfactory, acoustic) during their flight. On the basis of what flies do in nature, we designed laboratory tests to analyze the phenomenon of neuronal coincidence. We screened many mutants of genes involved in neuronal metabolism and the synaptic machinery.</p> <p>Conclusion</p> <p>Mutants of NO-dependent cyclase show a specifically-marked behaviour phenotype, but on the other hand they are associated with moderate biochemical defects. We show that these mutants present errors in integrative and/or coincident processing of signals, which are not reducible to the functions of the peripheral sensory cells.</p

MMP-9/RECK imbalance: a mechanism associated with high-grade cervical lesions and genital infection by Human Papillomavirus (HPV) and Chlamydia trachomatis

"Manuscript"BACKGROUND: Matrix metalloproteinases (MMP) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) toward squamous cell carcinoma (SCC) of the cervix. However, the role of MMPs in the inflammatory process associated with Chlamydia trachomatis infection concomitant with the carcinogenic process driven by HPV has not yet been addressed. In the present study, we analyzed the state of the MMP-9-RECK axis in cervical carcinogenesis. METHODS: The levels of MMP-9 and RECK expression were analyzed by immunocytochemistry in liquid-based cytology samples from 136 women with high-grade cervical lesions (CIN2/CIN3) and cervical SCC diagnosed by LLETZ, and in 196 women without cervical neoplasia or CIN1. Real-time qPCR was performed to analyze expression of MMP-9 and RECK in 15 cervical samples. The presence of HPV-DNA and other genital pathogens was evaluated by PCR. RESULTS: We found a higher expression of MMP-9 [OR, 4.2; 95% confidence interval (CI), 2.2-7.8] and lower expression of RECK (OR, 0.4; 95% CI, 0.2-0.7) in women with CIN2/CIN3/SCC when compared with women from the control group (no neoplasia/CIN1). A statistically significant association was also found between MMP-9/RECK imbalance and infection by alpha-9 HPV and C. trachomatis. The prevalence of C. trachomatis infection was significantly higher in women with high-grade cervical disease (OR, 3.7; 95% CI, 1.3-11.3). CONCLUSIONS: MMP-9/RECK imbalance in cervical smears is significantly associated with high-grade cervical diseases and infection by alpha-9 HPV and C. trachomatis. IMPACT: MMP-9/RECK imbalance during cervical inflammation induced by C. trachomatis might play a role in HPV-mediated cervical carcinogenesis.This work was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), numbers 2008/03232-1 (to L.L. Villa) and 2012/09746-2 (to M.G. Discacciati and S.S. Maria-Engler) and National Counsel of Technological and Scientific Development pharmaceutical innovation (CNPQ-INCT-if; to S.S. Maria-Engler)

Continued Neurogenesis in Adult Drosophila as a Mechanism for Recruiting Environmental Cue-Dependent Variants

Background The skills used by winged insects to explore their environment are strongly dependent upon the integration of neurosensory information comprising visual, acoustic and olfactory signals. The neuronal architecture of the wing contains a vast array of different sensors which might convey information to the brain in order to guide the trajectories during flight. In Drosophila, the wing sensory cells are either chemoreceptors or mechanoreceptors and some of these sensors have as yet unknown functions. The axons of these two functionally distinct types of neurons are entangled, generating a single nerve. This simple and accessible coincidental signaling circuitry in Drosophila constitutes an excellent model system to investigate the developmental variability in relation to natural behavioral polymorphisms. Methodology/Principal Findings A fluorescent marker was generated in neurons at all stages of the Drosophila life cycle using a highly efficient and controlled genetic recombination system that can be induced in dividing precursor cells (MARCM system, flybase web site). It allows fluorescent signals in axons only when the neuroblasts and/or neuronal cell precursors like SOP (sensory organ precursors) undergo division during the precedent steps. We first show that a robust neurogenesis continues in the wing after the adults emerge from the pupae followed by an extensive axonal growth. Arguments are presented to suggest that this wing neurogenesis in the newborn adult flies was influenced by genetic determinants such as the frequency dependent for gene and by environmental cues such as population density. Conclusions We demonstrate that the neuronal architecture in the adult Drosophila wing is unfinished when the flies emerge from their pupae. This unexpected developmental step might be crucial for generating non-heritable variants and phenotypic plasticity. This might therefore constitute an advantage in an unstable ecological system and explain much regarding the ability of Drosophila to robustly adapt to their environment

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Erarbeiten eines Modells als tierindividuelle Entscheidungshilfe (ist entsprechendes Tier behandlungswürdig oder nicht) bei einer Mastitiserkrankung beim Rind

keine vorhande

Mechanisms of Change in Digital Health Interventions for Mental Disorders in Youth: Systematic Review

BackgroundDigital health interventions (DHIs) are efficacious for several mental disorders in youth; however, integrated, evidence-based knowledge about the mechanisms of change in these interventions is lacking. ObjectiveThis systematic review aims to comprehensively evaluate studies on mediators and mechanisms of change in different DHIs for common mental disorders in children and adolescents. MethodsA systematic literature search of the electronic databases Cochrane Central Register of Controlled Trials, Embase, MEDLINE, and PsycINFO was conducted, complemented by backward and forward searches. Two independent reviewers selected studies for inclusion, extracted the data, and rated the methodological quality of eligible studies (ie, risk of bias and 8 quality criteria for process research). ResultsA total of 25 studies that have evaluated 39 potential mediators were included in this review. Cognitive mediators were the largest group of examined intervening variables, followed by a broad range of emotional and affective, interpersonal, parenting behavior, and other mediators. The mediator categories with the highest percentages of significant intervening variables were the groups of affective mediators (4/4, 100%) and combined cognitive mediators (13/19, 68%). Although more than three-quarters of the eligible studies met 5 or more quality criteria, causal conclusions have been widely precluded. ConclusionsThe findings of this review might guide the empirically informed advancement of DHIs, contributing to improved intervention outcomes, and the discussion of methodological recommendations for process research might facilitate mediation studies with more pertinent designs, allowing for conclusions with higher causal certainty in the future

Therapeutic processes in digital interventions for anxiety: A systematic review and meta-analytic structural equation modeling of randomized controlled trials

Domhardt M, Nowak H, Engler S, et al. Therapeutic processes in digital interventions for anxiety: A systematic review and meta-analytic structural equation modeling of randomized controlled trials. Clinical psychology review. 2021;90: 102084.While the efficacy of Internet- and mobile-based interventions (IMIs) for treating anxiety disorders is well established, there is no comprehensive overview about the underlying therapeutic processes so far. Thus, this systematic review and meta-analysis evaluated research on mediators and mechanisms of change in IMIs for adult anxiety disorders (PROSPERO: CRD42020185545). A systematic literature search was performed in five databases (i.e., CENTRAL, Embase, MEDLINE, PsycINFO and ClinicalTrials.gov). Two reviewers independently screened studies for inclusion, assessed the risk of bias and adherence to quality criteria for process research. Overall, 26 studies (N=6042) investigating 64 mediators were included. Samples consisted predominantly of participants with clinically relevant symptoms of generalized anxiety disorder and severe health anxiety, as well as of participants with non-clinically relevant anxiety symptoms. The largest group of examined mediators (45%) were cognitive variables, evincing also the second highest proportion of significance (19/29); followed in numbers by skills (examined: 22%; significant: 10/14) and a wide range of other (19%; 7/12), emotional/affective (11%; 2/7) and behavioral mediators (3%; 1/2). Meta-analytical synthesis of mediators, limited by a small number of eligible studies, was conducted by deploying a two-stage structural equation modeling approach, resulting in a significant indirect effect for negative thinking (k=3 studies) and non-significant indirect effects for combined cognitive variables, both in clinical (k=5) and non-clinical samples (k=3). The findings of this review might further the understanding on presumed change mechanisms in IMIs for anxiety, informing intervention development and the concurrent optimization of outcomes. Furthermore, by reviewing eligible mediation studies, we discuss methodological implications and recommendations for future process research, striving for causally robust findings. Future studies should investigate a broader range of variables as potential mediators, as well as to develop and apply original (digital) process and engagement measures to gather qualitative and high-resolution data on therapeutic processes. Copyright © 2021 Elsevier Ltd. All rights reserved

Mobile-based interventions for common mental disorders in youth: a systematic evaluation of pediatric health apps

The access to empirically-supported treatments for common mental disorders in children and adolescents is often limited. Mental health apps might extend service supplies, as they are deemed to be cost-efficient, scalable and appealing for youth. However, little is known about the quality of available apps. Therefore, we aimed to systematically evaluate current mobile-based interventions for pediatric anxiety, depression and posttraumatic stress disorder (PTSD).Systematic searches were conducted in Google Play Store and Apple App Store to identify relevant apps. To be eligible for inclusion, apps needed to be: (1) designed to target either anxiety, depression or PTSD in youth (0-18 years); (2) developed for children, adolescents or caregivers; (3) provided in English or German; (4) operative after download. The quality of eligible apps was assessed with two standardized rating systems (i.e., Mobile App Rating Scale (MARS) and ENLIGHT) independently by two reviewers.Overall, the searches revealed 3806 apps, with 15 mental health apps (0.39%) fulfilling our inclusion criteria. The mean overall scores suggested a moderate app quality (MARS: M = 3.59, SD = 0.50; ENLIGHT: M = 3.22, SD = 0.73). Moreover, only one app was evaluated in an RCT. The correlation of both rating scales was high (r = .936; p &amp;lt; .001), whereas no significant correlations were found between rating scales and user ratings (p &amp;gt; .05).Our results point to a rather poor overall app quality, and indicate an absence of scientific-driven development and lack of methodologically sound evaluation of apps. Thus, future high-quality research is required, both in terms of theoretically informed intervention development and assessment of mental health apps in RCTs. Furthermore, institutionalized best-practices that provide central information on different aspects of apps (e.g., effectiveness, safety, and data security) for patients, caregivers, stakeholders and mental health professionals are urgently needed

Recent advances in understanding plant-nematode interactions in monocots

Chapter EightInternational audienceMonocotyledonous crops including cereals, sugar cane, banana and cassava make an important tribute to agricultural commodities both in production and value worldwide. Diseases caused by nematodes in monocots are well documented and new data are emerging on interactions of these pathogens with some important monocotyledonous crop species. This review focuses on major monocotyledonous plant-nematode systems describing the biology and genetics of some interactions and highlighting efforts to identify and select resistant genetic resources. Molecular and histological data are presented having in the spotlight sedentary nematodes of the suborder Tylenchina. Histological observations are presented during nematode development and host resistance responses, comparing monocot and dicot plant hosts. Subsequently we focus on the recently published transcriptomics of monocotyledonous plant responses looking at specific metabolic changes and their role during plant-nematode interactions. Insights that may be learned from nematode interactions with dicotyledonous hosts are also discussed. As a final point, we look at nematode effectors during monocots-nematode interactions exploiting de novo transcriptome data produced from root-knot nematodes and cyst nematodes