Pro-inflammatory macrophage activation does not require inhibition of oxidative phosphorylation.

Pro-inflammatory macrophage activation is a hallmark example of how mitochondria serve as signaling organelles. Oxidative phosphorylation sharply decreases upon classical macrophage activation, as mitochondria are thought to shift from ATP production towards accumulating signals that amplify effector function. However, evidence is conflicting regarding whether this collapse in respiration is essential or dispensable.

A family of NADPH/NADP biosensors reveals in vivo dynamics of central redox metabolism across eukaryotes.

The NADPH/NADP redox couple is central to metabolism and redox signalling. NADP redox state is differentially regulated by distinct enzymatic machineries at the subcellular compartment level. Nonetheless, a detailed understanding of subcellular NADP redox dynamics is limited by the availability of appropriate tools.

An allosteric inhibitor of RhoGAP class-IX myosins suppresses the metastatic features of cancer cells.

Aberrant Ras homologous (Rho) GTPase signalling is a major driver of cancer metastasis, and GTPase-activating proteins (GAPs), the negative regulators of RhoGTPases, are considered promising targets for suppressing metastasis, yet drug discovery efforts have remained elusive. Here, we report the identification and characterization of adhibin, a synthetic allosteric inhibitor of RhoGAP class-IX myosins that abrogates ATPase and motor function, suppressing RhoGTPase-mediated modes of cancer cell metastasis. In human and murine adenocarcinoma and melanoma cell models, including three-dimensional spheroid cultures, we reveal anti-migratory and anti-adhesive properties of adhibin that originate from local disturbances in RhoA/ROCK-regulated signalling, affecting actin-dynamics and actomyosin-based cell-contractility.

TC10 differently controls the dynamics of Exo70 in growth cones of cortical and hippocampal neurons.

The exocyst is an octameric protein complex that acts as a tether for GOLGI-derived vesicles at the plasma membrane during exocytosis. It is involved in membrane expansion during axonal outgrowth. Exo70 is a major subunit of the exocyst complex and is controlled by TC10, a Rho family GTPase.

Decisive role of mDia-family formins in cell cortex function of highly adherent cells.

Cortical formins, pivotal for the assembly of linear actin filaments beneath the membrane, exert only minor effects on unconfined cell migration of weakly and moderately adherent cells. However, their impact on migration and mechanostability of highly adherent cells remains poorly understood. Here, we demonstrate that loss of cortical actin filaments generated by the formins mDia1 and mDia3 drastically compromises cell migration and mechanics in highly adherent fibroblasts.

Detailed analysis of Mdivi-1 effects on complex I and respiratory supercomplex assembly.

Several human diseases, including cancer and neurodegeneration, are associated with excessive mitochondrial fragmentation. In this context, mitochondrial division inhibitor (Mdivi-1) has been tested as a therapeutic to block the fission-related protein dynamin-like protein-1 (Drp1). Recent studies suggest that Mdivi-1 interferes with mitochondrial bioenergetics and complex I function.

In vivo anthelmintic activity of Combretum mucronatum schumach & Thonn leaf extract against Haemonchus contortus in goats.

Parasitic infections with gastrointestinal nematodes are a serious problem for the health and welfare of domestic animals and negatively affect the economics of animal production. Haemonchus contortus is a haematophagous nematode of small ruminants responsible for significant mortality and morbidity. In addition, the widespread resistance to synthetic anthelmintic drugs emphasizes the urgent need of alternative treatment options against haemonchosis.

Pro-inflammatory macrophage activation does not require inhibition of mitochondrial respiration.

Pro-inflammatory macrophage activation is a hallmark example of how mitochondria serve as signaling organelles. Upon classical macrophage activation, oxidative phosphorylation sharply decreases and mitochondria are repurposed to accumulate signals that amplify effector function. However, evidence is conflicting as to whether this collapse in respiration is essential or largely dispensable.

Palmitoylation of proteolipid protein M6 promotes tricellular junction assembly in epithelia of Drosophila.

Tricellular junctions (TCJs) seal epithelial cell vertices and are essential for tissue integrity and physiology, but how TCJs are assembled and maintained is poorly understood. In Drosophila, the transmembrane proteins Anakonda (Aka, also known as Bark), Gliotactin (Gli) and M6 organize occluding TCJs. Aka and M6 localize in an interdependent manner to vertices and act jointly to localize Gli, but how these proteins interact to assemble TCJs was not previously known.

Anthelmintic Activities of Extract and Ellagitannins from Phyllanthus urinaria against Caenorhabditis elegans and Zoonotic or Animal Parasitic Nematodes.

The aerial parts of are used in traditional medicine in West Africa against helminthiasis, but their anthelmintic potential has not been evaluated until now. Within the current study, a hydroacetonic extract (AWE) and fractions and isolated ellagitannins from were, therefore, tested against and the larvae of the animal parasites and . Compounds 1:  - 13: , mainly representing ellagitannins, were isolated using different chromatographic methods, and their structures were elucidated by HR-MS and H/C-NMR.

A molecular optomechanics approach reveals functional relevance of force transduction across talin and desmoplakin.

Many mechanobiological processes that govern development and tissue homeostasis are regulated on the level of individual molecular linkages, and a number of proteins experiencing piconewton-scale forces in cells have been identified. However, under which conditions these force-bearing linkages become critical for a given mechanobiological process is often still unclear. Here, we established an approach to revealing the mechanical function of intracellular molecules using molecular optomechanics.

PGC-1α Is a Master Regulator of Mitochondrial Lifecycle and ROS Stress Response.

Mitochondria play a major role in ROS production and defense during their life cycle. The transcriptional activator PGC-1α is a key player in the homeostasis of energy metabolism and is therefore closely linked to mitochondrial function. PGC-1α responds to environmental and intracellular conditions and is regulated by SIRT1/3, TFAM, and AMPK, which are also important regulators of mitochondrial biogenesis and function.

Acute manipulation and real-time visualization of membrane trafficking and exocytosis in Drosophila.

Intracellular trafficking of secretory proteins plays key roles in animal development and physiology, but so far, tools for investigating the dynamics of membrane trafficking have been limited to cultured cells. Here, we present a system that enables acute manipulation and real-time visualization of membrane trafficking through the reversible retention of proteins in the endoplasmic reticulum (ER) in living multicellular organisms. By adapting the "retention using selective hooks" (RUSH) approach to Drosophila, we show that trafficking of GPI-linked, secreted, and transmembrane proteins can be controlled with high temporal precision in intact animals and cultured organs.

Loss of respiratory complex I subunit NDUFB10 affects complex I assembly and supercomplex formation.

The orchestrated activity of the mitochondrial respiratory or electron transport chain (ETC) and ATP synthase convert reduction power (NADH, FADH) into ATP, the cell's energy currency in a process named oxidative phosphorylation (OXPHOS). Three out of the four ETC complexes are found in supramolecular assemblies: complex I, III, and IV form the respiratory supercomplexes (SC). The plasticity model suggests that SC formation is a form of adaptation to changing conditions such as energy supply, redox state, and stress.

Pathophysiological Mechanisms of Cardiac Dysfunction in Transgenic Mice with Viral Myocarditis.

Viral myocarditis is pathologically associated with RNA viruses such as coxsackievirus B3 (CVB3), or more recently, with SARS-CoV-2, but despite intensive research, clinically proven treatment is limited. Here, by use of a transgenic mouse strain (TG) containing a CVB3ΔVP0 genome we unravel virus-mediated cardiac pathophysiological processes in vivo and in vitro. Cardiac function, pathologic ECG alterations, calcium homeostasis, intracellular organization and gene expression were significantly altered in transgenic mice.

Anthelmintic Agents from African Medicinal Plants: Review and Prospects.

Soil-transmitted helminthiasis affects more than 1.5 billion people globally and largely remains a sanitary problem in Africa. These infections place a huge economic burden on poor countries and affect livestock production, causing substantial economic losses and poor animal health.

Multiplexed Molecular Tension Sensor Measurements Using PIE-FLIM.

Genetically encoded Förster Resonance Energy Transfer (FRET)-based tension sensors were developed to enable the quantification of piconewton (pN)-scale forces that act across distinct proteins in living cells and organisms. An important extension of this technology is the multiplexing of tension sensors to monitor several independent FRET probes in parallel. Here we describe how pulsed interleaved excitation (PIE)-fluorescence lifetime imaging microscopy (FLIM) can be implemented to enable the analysis of two co-expressed tension sensor constructs.

Inner mitochondrial membrane structure and fusion dynamics are altered in senescent human iPSC-derived and primary rat cardiomyocytes.

Dysfunction of the aging heart is a major cause of death in the human population. Amongst other tasks, mitochondria are pivotal to supply the working heart with ATP. The mitochondrial inner membrane (IMM) ultrastructure is tailored to meet these demands and to provide nano-compartments for specific tasks.

Genetically encoded dual fluorophore reporters for graded oxygen-sensing in light microscopy.

Hypoxia is an essential regulator of cell metabolism, affects cell migration and angiogenesis during development and contributes to a wide range of pathological conditions. Multiple techniques to assess hypoxia through oxygen-imaging have been developed. However, significant limitations include low spatiotemporal resolution, limited tissue penetration of exogenous probes and non-dynamic signals due to irreversible probe-chemistry.

Condensed tannins act as anthelmintics by increasing the rigidity of the nematode cuticle.

Tannins and tanniferous plant extracts have been discussed as sustainable means for helminth control in the past two decades in response to a dramatic increase of resistances towards standard anthelmintics. While their bioactivities have been broadly investigated in vitro and in vivo, less is known about their mode of action in nematodes, apart from their protein binding properties. In the current study we therefore investigated the impact of a phytochemically well characterized plant extract from Combretum mucronatum, known to contain procyanidins as the active compounds, on the model organism Caenorhabditis elegans.

Mutations in MYO9B are associated with Charcot-Marie-Tooth disease type 2 neuropathies and isolated optic atrophy.

Background And Purpose: Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders caused by mutations in at least 100 genes. However, approximately 60% of cases with axonal neuropathies (CMT2) still remain without a genetic diagnosis. We aimed at identifying novel disease genes responsible for CMT2.

The RhoGAP-myosin Myo9b regulates ocular lens pit morphogenesis.

Background: During eye development the lens placode invaginates to form the lens pit. Further bending of lens epithelium and separation from ectoderm leads eventually to a spherical lens vesicle with enclosed extracellular fluid. Changes in epithelial morphology involve the actin cytoskeleton and its regulators.

PI(4,5)P2 controls slit diaphragm formation and endocytosis in Drosophila nephrocytes.

Drosophila nephrocytes are an emerging model system for mammalian podocytes and proximal tubules as well as for the investigation of kidney diseases. Like podocytes, nephrocytes exhibit characteristics of epithelial cells, but the role of phospholipids in polarization of these cells is yet unclear. In epithelia, phosphatidylinositol(4,5)bisphosphate (PI(4,5)P2) and phosphatidylinositol(3,4,5)-trisphosphate (PI(3,4,5)P3) are asymmetrically distributed in the plasma membrane and determine apical-basal polarity.

Tracheal tube fusion in Drosophila involves release of extracellular vesicles from multivesicular bodies.

Extracellular vesicles (EVs) comprise diverse types of cell-released membranous structures that are thought to play important roles in intercellular communication. While the formation and functions of EVs have been investigated extensively in cultured cells, studies of EVs in vivo have remained scarce. We report here that EVs are present in the developing lumen of tracheal tubes in Drosophila embryos.