The Drosophila LEM-domain protein MAN1 antagonizes BMP signaling at the neuromuscular junction and the wing crossveins

AbstractBMP signaling responses are refined by distinct secreted and intracellular antagonists in different cellular and temporal contexts. Here, we show that the nuclear LEM-domain protein MAN1 is a tissue-specific antagonist of BMP signaling in Drosophila. MAN1 contains two potential Mad-binding sites. We generated MAN1ΔC mutants, harbouring a MAN1 protein that lacks part of the C-terminus including the RNA recognition motif, a putative Mad-binding domain. MAN1ΔC mutants show wing crossvein (CV) patterning defects but no detectable alterations in nuclear morphology. MAN1ΔC pupal wings display expanded phospho-Mad (pMad) accumulation and ectopic expression of the BMP-responsive gene crossveinless-2 (cv-2) indicating that MAN1 restricts BMP signaling. Conversely, MAN1 overexpression in wing imaginal discs inhibited crossvein development and BMP signaling responses. MAN1 is expressed at high levels in pupal wing veins and can be activated in intervein regions by ectopic BMP signaling. The specific upregulation of MAN1 in pupal wing veins may thus represent a negative feedback circuit that limits BMP signaling during CV formation. MAN1ΔC flies also show reduced locomotor activity, and electrophysiology recordings in MAN1ΔC larvae uncover a new presynaptic role of MAN1 at the neuromuscular junction (NMJ). Genetic interaction experiments suggest that MAN1 is a BMP signaling antagonist both at the NMJ and during CV formation

Linear-Time Temporal Answer Set Programming

[Abstract]: In this survey, we present an overview on (Modal) Temporal Logic Programming in view of its application to Knowledge Representation and Declarative Problem Solving. The syntax of this extension of logic programs is the result of combining usual rules with temporal modal operators, as in Linear-time Temporal Logic (LTL). In the paper, we focus on the main recent results of the non-monotonic formalism called Temporal Equilibrium Logic (TEL) that is defined for the full syntax of LTL but involves a model selection criterion based on Equilibrium Logic, a well known logical characterization of Answer Set Programming (ASP). As a result, we obtain a proper extension of the stable models semantics for the general case of temporal formulas in the syntax of LTL. We recall the basic definitions for TEL and its monotonic basis, the temporal logic of Here-and-There (THT), and study the differences between finite and infinite trace length. We also provide further useful results, such as the translation into other formalisms like Quantified Equilibrium Logic and Second-order LTL, and some techniques for computing temporal stable models based on automata constructions. In the remainder of the paper, we focus on practical aspects, defining a syntactic fragment called (modal) temporal logic programs closer to ASP, and explaining how this has been exploited in the construction of the solver telingo, a temporal extension of the well-known ASP solver clingo that uses its incremental solving capabilities.Xunta de Galicia; ED431B 2019/03We are thankful to the anonymous reviewers for their thorough work and their useful suggestions that have helped to improve the paper. A special thanks goes to Mirosaw Truszczy´nski for his support in improving the quality of our paper. We are especially grateful to David Pearce, whose help and collaboration on Equilibrium Logic was the seed for a great part of the current paper. This work was partially supported by MICINN, Spain, grant PID2020-116201GB-I00, Xunta de Galicia, Spain (GPC ED431B 2019/03), R´egion Pays de la Loire, France, (projects EL4HC and etoiles montantes CTASP), European Union COST action CA-17124, and DFG grants SCHA 550/11 and 15, Germany

In Vivo Assembly of Photosystem I-Hydrogenase Chimera for In Vitro PhotoH2 Production

Funding Information: P.W., A.F., and J.A. contributed equally to this work. The authors are grateful to the Bundesministerium für Bildung und Forschung (BMBF) in the framework of the project CyFun (03SF0652A). The authors also thank Prof. Wolfgang Lubitz (Max Planck Institute for Chemical Energy Conversion, Mülheim an der Ruhr) for providing the DvMF[NiFe]-H2ase used for the fabrication of the H2 microsensor. Part of the project was funded by the research training group GRK2341 “Microbial Substrate Conversion (MiCon)” of the German research council (DFG) and the Dietmar Hopp Stiftung. P.W. is grateful for the financial support provided by the China Scholarship Council (CSC). F.C. is grateful to the support provided by FCT–Fundação para a Ciência e a Tecnologia, I.P. through MOSTMICRO-ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020). Open access funding enabled and organized by Projekt DEAL. Funding Information: P.W., A.F., and J.A. contributed equally to this work. The authors are grateful to the Bundesministerium für Bildung und Forschung (BMBF) in the framework of the project CyFun (03SF0652A). The authors also thank Prof. Wolfgang Lubitz (Max Planck Institute for Chemical Energy Conversion, Mülheim an der Ruhr) for providing the DvMF[NiFe]‐Hase used for the fabrication of the H microsensor. Part of the project was funded by the research training group GRK2341 “Microbial Substrate Conversion (MiCon)” of the German research council (DFG) and the Dietmar Hopp Stiftung. P.W. is grateful for the financial support provided by the China Scholarship Council (CSC). F.C. is grateful to the support provided by FCT–Fundação para a Ciência e a Tecnologia, I.P. through MOSTMICRO‐ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020). 2 2 Publisher Copyright: © 2023 The Authors. Advanced Energy Materials published by Wiley-VCH GmbH.Photosynthetic hydrogen (photoH2) production is an elegant approach to storing solar energy. The most efficient strategy is to couple the hydrogen-producing enzyme, the hydrogenase (H2ase), directly to photosystem I (PSI), which is a light-driven nanomachine found in photosynthetic organisms. PSI–H2ase fusions have been tested in vivo and in vitro. Both approaches have each their specific advantages and drawbacks. Here, a system to combine both approaches by assembling PSI–H2ase fusions in vivo for in vitro photoH2 production is established. For this, cyanobacterial PSI–H2ase fusion mutants are generated and characterized concerning photoH2 production in vivo. The chimeric protein is purified and embedded in a redox polymer on an electrode where it successfully produces photoH2 in vitro. The combination of in vivo and in vitro processes comes along with reciprocal benefits. The in vivo assembly ensures that the chimeric protein is fully functional and suited for the fabrication of bioelectrodes in vitro. At the same time, the photoelectrochemical in vitro characterization now permits to analyze the assemblies in detail. This will open avenues to optimize in vivo and in vitro approaches for photoH2 production in a target-oriented manner in the future.publishersversionpublishe

Adult-Adult and Adult-Child/Adolescent Online Sexual Interactions: An Exploratory Self-Report Study on the Role of Situational Factors

Alcohol intoxication, sexual arousal, and negative emotional states have been found to precede certain sexual behaviors. Using data from an online self-report survey distributed to adults (N&nbsp;=&nbsp;717; 423 men and 304 women), we compared adults with adult online sexual interactions (n&nbsp;=&nbsp;640; 89.3%) to adults with interactions with a child or an adolescent (n&nbsp;=&nbsp;77; 10.7%) on how much they reported being affected by the following factors surrounding the time of the interactions: alcohol intoxication, sexual arousal, sadness, boredom, stress, and shame. We found that those with a child or adolescent contact reported higher sexual arousal and more shame before the interaction, compared with those with an adult contact. In addition, the levels of negative emotional states varied when levels before the interactions were compared with levels after the interactions, suggesting that engaging in online sexual interactions alleviated negative emotional states, at least temporarily. The alleviatory effects, however, were accompanied by higher levels of shame after the interactions. Overall, adults that engage in online sexual interactions have remarkably similar perceptions of the situation surrounding these activities, independent of the age of their online contacts. Limitations of the study are discussed.</p

Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features

Diffuse leptomeningeal glioneuronal tumors (DLGNT) represent rare CNS neoplasms which have been included in the 2016 update of the WHO classification. The wide spectrum of histopathological and radiological features can make this enigmatic tumor entity difficult to diagnose. In recent years, large-scale genomic and epigenomic analyses have afforded insight into key genetic alterations occurring in multiple types of brain tumors and provide unbiased, complementary tools to improve diagnostic accuracy. Through genome-wide DNA methylation screening of &gt; 25,000 tumors, we discovered a molecularly distinct class comprising 30 tumors, mostly diagnosed histologically as DLGNTs. Copy-number profiles derived from the methylation arrays revealed unifying characteristics, including loss of chromosomal arm 1p in all cases. Furthermore, this molecular DLGNT class can be subdivided into two subgroups [DLGNT methylation class (MC)-1 and DLGNT methylation class (MC)-2], with all DLGNT-MC-2 additionally displaying a gain of chromosomal arm 1q. Co-deletion of 1p/19q, commonly seen in IDH-mutant oligodendroglioma, was frequently observed in DLGNT, especially in DLGNT-MC-1 cases. Both subgroups also had recurrent genetic alterations leading to an aberrant MAPK/ERK pathway, with KIAA1549:BRAF fusion being the most frequent event. Other alterations included fusions of NTRK1/2/3 and TRIM33:RAF1, adding up to an MAPK/ERK pathway activation identified in 80% of cases. In the DLGNT-MC-1 group, age at diagnosis was significantly lower (median 5 vs 14 years, p &lt; 0.01) and clinical course less aggressive (5-year OS 100, vs 43% in DLGNT-MC-2). Our study proposes an additional molecular layer to the current histopathological classification of DLGNT, of particular use for cases without typical morphological or radiological characteristics, such as diffuse growth and radiologic leptomeningeal dissemination. Recurrent 1p deletion and MAPK/ERK pathway activation represent diagnostic biomarkers and therapeutic targets, respectively—laying the foundation for future clinical trials with, e.g., MEK inhibitors that may improve the clinical outcome of patients with DLGNT

Bioelectrocatalytic CO₂ Reduction by Redox Polymer-Wired Carbon Monoxide Dehydrogenase Gas Diffusion Electrodes

The development of electrodes for efficient CO₂ reduction while forming valuable compounds is critical. The use of enzymes as catalysts provides the advantage of high catalytic activity in combination with highly selective transformations. We describe the electrical wiring of a carbon monoxide dehydrogenase II from Carboxydothermus hydrogenoformans (ChCODH II) using a cobaltocene-based low-potential redox polymer for the selective reduction of CO₂ to CO over gas diffusion electrodes. High catalytic current densities of up to −5.5 mA cm¯² are achieved, exceeding the performance of previously reported bioelectrodes for CO₂ reduction based on either carbon monoxide dehydrogenases or formate dehydrogenases. The proposed bioelectrode reveals considerable stability with a half-life of more than 20 h of continuous operation. Product quantification using gas chromatography confirmed the selective transformation of CO₂ into CO without any parasitic co-reactions at the applied potentials

Experimental traumatic brain injury

Traumatic brain injury, a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. These pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far. Experimental models are essential for further clarification of the highly complex pathology of traumatic brain injury towards the development of novel treatments. Among the rodent models of traumatic brain injury the most commonly used are the weight-drop, the fluid percussion, and the cortical contusion injury models. As the entire spectrum of events that might occur in traumatic brain injury cannot be covered by one single rodent model, the design and choice of a specific model represents a major challenge for neuroscientists. This review summarizes and evaluates the strengths and weaknesses of the currently available rodent models for traumatic brain injury