Differential impact of infection on the microbiota of and .

The Western honey bee () is a vital agricultural pollinator whose populations are threatened by the parasitic mite destructor and associated pathogens. While the impact of species on honey bees, particularly larvae causing American foulbrood, is documented, their effect on the microbiota of mites remains unclear. This study aimed to investigate the influence of sp.

Functional redundancy and niche specialization in honeybee and Varroa microbiomes.

The honeybee (Apis mellifera) is a key pollinator critical to global agriculture, facing threats from various stressors, including the ectoparasitic Varroa mite (Varroa destructor). Previous studies have identified shared bacteria between Varroa mites and honeybees, yet it remains unclear if these bacteria assemble similarly in both species. This study builds on existing knowledge by investigating co-occurrence patterns in the microbiomes of both Varroa mites and honeybees, shedding light on potential interactions.

Alcohol extract of the gypsy mushroom (Cortinarius caperatus) inhibits the development of Deformed wing virus infection in western honey bee (Apis mellifera).

Deformed wing virus (DWV) transmitted by the parasitic mite Varroa destructor is one of the most significant factors contributing to massive losses of managed colonies of western honey bee (Apis mellifera) subspecies of European origin reported worldwide in recent decades. Despite this fact, no antiviral treatment against honey bee viruses is currently available for practical applications and the level of viral infection can only be controlled indirectly by reducing the number of Varroa mites in honey bee colonies. In this study, we investigated the antiviral potential of the gypsy mushroom (Cortinarius caperatus) to reduce DWV infection in honey bees.

Gut microbiota assembly of Gotland varroa-surviving honey bees excludes major viral pathogens.

The spread of the parasite Varroa destructor and associated viruses has resulted in massive honey bee colony losses with considerable economic and ecological impact. The gut microbiota has a major role in shaping honey bees tolerance and resistance to parasite infestation and viral infection, but the contribution of viruses to the assembly of the host microbiota in the context of varroa resistance and susceptibility remains unclear. Here, we used a network approach including viral and bacterial nodes to characterize the impact of five viruses, Apis Rhabdovirus-1 (ARV-1), Black Queen Cell virus (BQCV), Lake Sinai virus (LSV), Sacbrood virus (SBV) and Deformed wing virus (DWV) on the gut microbiota assembly of varroa-susceptible and Gotland varroa-surviving honey bees.

Honeybees control the gas permeability of brood and honey cappings.

Some bee species use wax to build their nests. They store honey and raise their brood in cells made entirely from wax. How can the bee brood breathe and develop properly when sealed in wax cells? We compared the chemical composition and structural properties of the honey cappings and worker brood cappings of the honeybee , measured the worker brood respiration, and calculated the CO gradients across the two types of cappings.

Downregulation of respiratory complex I mediates major signalling changes triggered by TOR activation.

Mitochondrial dysfunctions belong amongst the most common metabolic diseases but the signalling networks that lead to the manifestation of a disease phenotype are often not well understood. We identified the subunits of respiratory complex I, III and IV as mediators of major signalling changes during Drosophila wing disc development. Their downregulation in larval wing disc leads to robust stimulation of TOR activity, which in turn orchestrates a complex downstream signalling network.

Lime is a new protein linking immunity and metabolism in Drosophila.

The proliferation, differentiation and function of immune cells in vertebrates, as well as in the invertebrates, is regulated by distinct signalling pathways and crosstalk with systemic and cellular metabolism. We have identified the Lime gene (Linking Immunity and Metabolism, CG18446) as one such connecting factor, linking hemocyte development with systemic metabolism in Drosophila. Lime is expressed in larval plasmatocytes and the fat body and regulates immune cell type and number by influencing the size of hemocyte progenitor populations in the lymph gland and in circulation.

Metabolism in time and space - exploring the frontier of developmental biology.

Despite the fact that metabolic studies played a prominent role in the early history of developmental biology research, the field of developmental metabolism was largely ignored following the advent of modern molecular biology. Metabolism, however, has recently re-emerged as a focal point of biomedical studies and, as a result, developmental biologists are once again exploring the chemical and energetic forces that shape growth, development and maturation. In May 2017, a diverse group of scientists assembled at the EMBO/EMBL Symposium 'Metabolism in Time and Space' to discuss how metabolism influences cellular and developmental processes.

The silent information regulator 1 (Sirt1) is a positive regulator of the Notch pathway in Drosophila.

The silent information regulator 1 (Sirt1) has been shown to have negative effects on the Notch pathway in several contexts. We bring evidence that Sirt1 has a positive effect on Notch activation in Drosophila, in the context of sensory organ precursor specification and during wing development. The phenotype of Sirt1 mutant resembles weak Notch loss-of-function phenotypes, and genetic interactions of Sirt1 with the components of the Notch pathway also suggest a positive role for Sirt1 in Notch signalling.

Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle.

Glycolytic shift is a characteristic feature of rapidly proliferating cells, such as cells during development and during immune response or cancer cells, as well as of stem cells. It results in increased glycolysis uncoupled from mitochondrial respiration, also known as the Warburg effect. Notch signalling is active in contexts where cells undergo glycolytic shift.

A Serrate-Notch-Canoe complex mediates essential interactions between glia and neuroepithelial cells during Drosophila optic lobe development.

It is firmly established that interactions between neurons and glia are fundamental across species for the correct establishment of a functional brain. Here, we found that the glia of the Drosophila larval brain display an essential non-autonomous role during the development of the optic lobe. The optic lobe develops from neuroepithelial cells that proliferate by dividing symmetrically until they switch to asymmetric/differentiative divisions that generate neuroblasts.

Notch cooperates with Lozenge/Runx to lock haemocytes into a differentiation programme.

The diverse functions of Notch signalling imply that it must elicit context-specific programmes of gene expression. With the aim of investigating how Notch drives cells to differentiate, we have used a genome-wide approach to identify direct Notch targets in Drosophila haemocytes (blood cells), where Notch promotes crystal cell differentiation. Many of the identified Notch-regulated enhancers contain Runx and GATA motifs, and we demonstrate that binding of the Runx protein Lozenge (Lz) is required for enhancers to be competent to respond to Notch.

Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes.

Dynamic activity of signaling pathways, such as Notch, is vital to achieve correct development and homeostasis. However, most studies assess output many hours or days after initiation of signaling, once the outcome has been consolidated. Here we analyze genome-wide changes in transcript levels, binding of the Notch pathway transcription factor, CSL [Suppressor of Hairless, Su(H), in Drosophila], and RNA Polymerase II (Pol II) immediately following a short pulse of Notch stimulation.

Dissecting the mechanisms of Notch induced hyperplasia.

The outcome of the Notch pathway on proliferation depends on cellular context, being growth promotion in some, including several cancers, and growth inhibition in others. Such disparate outcomes are evident in Drosophila wing discs, where Notch overactivation causes hyperplasia despite having localized inhibitory effects on proliferation. To understand the underlying mechanisms, we have used genomic strategies to identify the Notch-CSL target genes directly activated during wing disc hyperplasia.

Metabolic sensors and their interplay with cell signalling and transcription.

There is an intimate, yet poorly understood, link between cellular metabolic status, cell signalling and transcription. Central metabolic pathways are under the control of signalling pathways and, vice versa, the cellular metabolic profile influences cell signalling through the incorporation of various metabolic sensors into the signalling networks. Thus information about nutrients availability directly and crucially influences crucial cell decisions.

Chromatin modification of Notch targets in olfactory receptor neuron diversification.

Neuronal-class diversification is central during neurogenesis. This requirement is exemplified in the olfactory system, which utilizes a large array of olfactory receptor neuron (ORN) classes. We discovered an epigenetic mechanism in which neuron diversity is maximized via locus-specific chromatin modifications that generate context-dependent responses from a single, generally used intracellular signal.

Epigenetic changes at Il12rb2 and Tbx21 in relation to plasticity behavior of Th17 cells.

Plasticity within Th cell populations may play a role in enabling site-specific immune responses to infections while limiting tissue destruction. Epigenetic processes are fundamental to such plasticity; however, to date, most investigations have focused on in vitro-generated T cells. In this study, we have examined the molecular mechanisms underpinning murine Th17 plasticity in vivo by assessing H3K4 and H3K27 trimethylation marks at Tbx21, Rorc, Il17a, Ifng, and Il12rb2 loci in purified ex vivo-isolated and in vitro-generated Th17 cells.

Specificity of Notch pathway activation: twist controls the transcriptional output in adult muscle progenitors.

Cell-cell signalling mediated by Notch regulates many different developmental and physiological processes and is involved in a variety of human diseases. Activation of Notch impinges directly on gene expression through the Suppressor of Hairless [Su(H)] DNA-binding protein. A major question that remains to be elucidated is how the same Notch signalling pathway can result in different transcriptional responses depending on the cellular context and environment.

Direct response to Notch activation: signaling crosstalk and incoherent logic.

Notch is the receptor in one of a small group of conserved signaling pathways that are essential at multiple stages in development. Although the mechanism of transduction impinges directly on the nucleus to regulate transcription through the CSL [CBF-1/Su(H)/LAG-1] [corrected] DNA binding protein, there are few known direct target genes. Thus, relatively little is known about the immediate cellular consequences of Notch activation.

Grainy head promotes expression of septate junction proteins and influences epithelial morphogenesis.

Transcription factors of the Grainy head (Grh) family are required in epithelia to generate the impermeable apical layer that protects against the external environment. This function is conserved in vertebrates and invertebrates, despite the differing molecular composition of the protective barrier. Epithelial cells also have junctions that create a paracellular diffusion barrier (tight or septate junctions).

Gene-specific targeting of the histone chaperone asf1 to mediate silencing.

The histone chaperone Asf1 assists in chromatin assembly and remodeling during replication, transcription activation, and gene silencing. However, it has been unclear to what extent Asf1 could be targeted to specific loci via interactions with sequence-specific DNA-binding proteins. Here, we show that Asf1 contributes to the repression of Notch target genes, as depletion of Asf1 in cells by RNAi causes derepression of the E(spl) Notch-inducible genes.

Notch activation stimulates transient and selective binding of Su(H)/CSL to target enhancers.

The CSL [CBF1/Su(H)/Lag2] proteins [Su(H) in Drosophila] are implicated in repression and activation of Notch target loci. Prevailing models imply a static association of these DNA-binding transcription factors with their target enhancers. Our analysis of Su(H) binding and chromatin-associated features at 11 E(spl) Notch target genes before and after Notch revealed large differences in Su(H) occupancy at target loci that correlated with the presence of polymerase II and other marks of transcriptional activity.

The transcriptional repressor REST is a critical regulator of the neurosecretory phenotype.

Release of distinct cellular cargoes in response to specific stimuli is a process fundamental to all higher eukaryotes and controlled by the regulated secretory pathway (RSP). However, the mechanism by which genes involved in the RSP are selectively expressed, leading to the establishment and appropriate functioning of regulated secretion remaining largely unknown. Using the rat pheochromocytoma cell line PC12, we provide evidence that, by controlling expression of many genes involved in the RSP, the transcriptional repressor REST can regulate this pathway and hence the neurosecretory phenotype.

Hairless-mediated repression of notch target genes requires the combined activity of Groucho and CtBP corepressors.

Notch signal transduction centers on a conserved DNA-binding protein called Suppressor of Hairless [Su(H)] in Drosophila species. In the absence of Notch activation, target genes are repressed by Su(H) acting in conjunction with a partner, Hairless, which contains binding motifs for two global corepressors, CtBP and Groucho (Gro). Usually these corepressors are thought to act via different mechanisms; complexed with other transcriptional regulators, they function independently and/or redundantly.

Multiple promoters drive tissue-specific expression of the human M muscarinic acetylcholine receptor gene.

Despite the wealth of information on the functional and pharmacological properties of the M2 muscarinic receptor, we know relatively little of structure and regulation of the M2 receptor gene. Here, we describe the organisation of the human M2 gene and its promoters. Four exons are present in the 5' untranslated region of the human M2 mRNA distributed over 146 kb on chromosome 7 which produce eight different splice variants in the IMR-32 neuroblastoma cell line.