The role of nuclear Ca2+ in maintaining neuronal homeostasis and brain health.

Nuclear Ca2+ has emerged as one of the most potent mediators of the dialogue between neuronal synapses and the nucleus that regulates heterochromatin states, transcription factor activity, nuclear morphology and neuronal gene expression induced by synaptic activity. Recent studies underline the importance of nuclear Ca2+ signaling in long-lasting, activity-induced adaptation and maintenance of proper brain function. Diverse forms of neuroadaptation require transient nuclear Ca2+ signaling and cyclic AMP-responsive element-binding protein (CREB1, referred to here as CREB) as its prime target, which works as a tunable switch to drive and modulate specific gene expression profiles associated with memory, pain, addiction and neuroprotection.

Visualization of Protein Coding, Long Noncoding, and Nuclear RNAs by Fluorescence in Situ Hybridization in Sections of Shoot Apical Meristems and Developing Flowers.

In addition to transcriptional regulation, gene expression is further modulated through mRNA spatiotemporal distribution, by RNA movement between cells, and by RNA localization within cells. Here, we have adapted RNA fluorescence in situ hybridization (FISH) to explore RNA localization in Arabidopsis (). We show that RNA FISH on sectioned material can be applied to investigate the tissue and subcellular localization of meristem and flower development genes, cell cycle transcripts, and plant long noncoding RNAs.

Primary wall cellulose synthase regulates shoot apical meristem mechanics and growth.

How organisms attain their specific shapes and modify their growth patterns in response to environmental and chemical signals has been the subject of many investigations. Plant cells are at high turgor pressure and are surrounded by a rigid yet flexible cell wall, which is the primary determinant of plant growth and morphogenesis. Cellulose microfibrils, synthesized by plasma membrane-localized cellulose synthase complexes, are major tension-bearing components of the cell wall that mediate directional growth.

Nitrate modulates stem cell dynamics in shoot meristems through cytokinins.

The shoot apical meristem (SAM) is responsible for the generation of all the aerial parts of plants. Given its critical role, dynamical changes in SAM activity should play a central role in the adaptation of plant architecture to the environment. Using quantitative microscopy, grafting experiments, and genetic perturbations, we connect the plant environment to the SAM by describing the molecular mechanism by which cytokinins signal the level of nutrient availability to the SAM.

Regulation of Meristem Morphogenesis by Cell Wall Synthases in Arabidopsis.

The cell walls of the shoot apical meristem (SAM), containing the stem cell niche that gives rise to the above-ground tissues, are crucially involved in regulating differentiation. It is currently unknown how these walls are built and refined or their role, if any, in influencing meristem developmental dynamics. We have combined polysaccharide linkage analysis, immuno-labeling, and transcriptome profiling of the SAM to provide a spatiotemporal plan of the walls of this dynamic structure.

An epidermis-driven mechanism positions and scales stem cell niches in plants.

How molecular patterning scales to organ size is highly debated in developmental biology. We explore this question for the characteristic gene expression domains of the plant stem cell niche residing in the shoot apical meristem. We show that a combination of signals originating from the epidermal cell layer can correctly pattern the key gene expression domains and notably leads to adaptive scaling of these domains to the size of the tissue.

A Developmental Framework for Graft Formation and Vascular Reconnection in Arabidopsis thaliana.

Plant grafting is a biologically important phenomenon involving the physical joining of two plants to generate a chimeric organism. It is widely practiced in horticulture and used in science to study the long-distance movement of molecules. Despite its widespread use, the mechanism of graft formation and vascular reconnection is not well understood.

Synaptic bouton properties are tuned to best fit the prevailing firing pattern.

The morphology of presynaptic specializations can vary greatly ranging from classical single-release-site boutons in the central nervous system to boutons of various sizes harboring multiple vesicle release sites. Multi-release-site boutons can be found in several neural contexts, for example at the neuromuscular junction (NMJ) of body wall muscles of Drosophila larvae. These NMJs are built by two motor neurons forming two types of glutamatergic multi-release-site boutons with two typical diameters.

Red light as a 12-oxo-leukotriene B₄ antagonist: an explanation for the efficacy of intensive red light in the therapy of peripheral inflammatory diseases.

To explain the successful treatment of various inflammatory diseases by using intensive red light, a non-linear theory is presented for the interaction of electric dipoles with light involving frequency doubling. It is applied to analyze the influence of light on organic molecules with permanent electric dipoles. The molecule 5-hydroxy-12-oxo-(5S,6Z,8E,10E,14Z)-6,8,10,14-eicosatetraenoic acid, 12-oxo-leukotriene B4 (12-Oxo-LTB4, an intermediate in the lipoxygenase-catalyzed path of arachidonic acid metabolism), is suspected to play a major role in the healing process, as, first, it plays a key role in the metabolism of leukotriene B4 (LTB4), which in many diseases acts as a source of inflammatory reactions; second, its dipole resonance is located at a wavelength of 316 nm, which can be excited by a 632 nm source through frequency doubling.

A regulatory framework for shoot stem cell control integrating metabolic, transcriptional, and phytohormone signals.

Plants continuously maintain pluripotent stem cells embedded in specialized tissues called meristems, which drive long-term growth and organogenesis. Stem cell fate in the shoot apical meristem (SAM) is controlled by the homeodomain transcription factor WUSCHEL (WUS) expressed in the niche adjacent to the stem cells. Here, we demonstrate that the bHLH transcription factor HECATE1 (HEC1) is a target of WUS and that it contributes to SAM function by promoting stem cell proliferation, while antagonizing niche cell activity.

Requirement for nuclear calcium signaling in Drosophila long-term memory.

Calcium is used throughout evolution as an intracellular signal transducer. In the mammalian central nervous system, calcium mediates the dialogue between the synapse and the nucleus that is required for transcription-dependent persistent neuronal adaptations. A role for nuclear calcium signaling in similar processes in the invertebrate brain has yet to be investigated.

Cardiac surgery in cases of myeloproliferative neoplasm: risk factor for stroke.

Objectives: a history of myeloproliferative neoplasms is considered to increase the risks in cardiac surgery. In patients with myeloproliferative neoplasms, increased rates of perioperative infections and thromboembolic complications are suspected, but studies analyzing the impact of myeloproliferative neoplasms on results after cardiac surgery are lacking.

Methods: 13 patients with the diagnosis of myeloproliferative neoplasm underwent cardiac surgery.

Toxic and non-toxic aggregates from the SBMA and normal forms of androgen receptor have distinct oligomeric structures.

Hormone-dependent aggregation of the androgen receptor (AR) with a polyglutamine (polyQ) stretch amplification (>38) is considered to be the causative agent of the neurodegenerative disorder spinal and bulbar muscular atrophy (SBMA), consistent with related neurodegenerative diseases involving polyQ-extended proteins. In spite of the widespread acceptance of this common causal hypothesis, little attention has been paid to its apparent incompatibility with the observation of AR aggregation in healthy individuals with no polyQ stretch amplification. Here we used atomic force microscopy (AFM) to characterize sub-micrometer scale aggregates of the wild-type (22 glutamines) and the SBMA form (65 glutamines), as well as a polyQ deletion mutant (1 glutamine) and a variant with a normal length polyQ stretch but with a serine to alanine double mutation elsewhere in the protein.

Cardiac surgery and hematologic malignancies: a retrospective single-center analysis of 56 consecutive patients.

Objective: Patients with a history of hematologic malignancies (HMs) are considered high-risk candidates for cardiac surgery. Increased perioperative rates of infections, thrombo-embolic complications, and bleeding disorders are reported. However, low patient numbers and lack of control groups limit all published studies.

Transcriptional control of a plant stem cell niche.

Despite the independent evolution of multicellularity in plants and animals, the basic organization of their stem cell niches is remarkably similar. Here, we report the genome-wide regulatory potential of WUSCHEL, the key transcription factor for stem cell maintenance in the shoot apical meristem of the reference plant Arabidopsis thaliana. WUSCHEL acts by directly binding to at least two distinct DNA motifs in more than 100 target promoters and preferentially affects the expression of genes with roles in hormone signaling, metabolism, and development.

Circadian plasticity in photoreceptor cells controls visual coding efficiency in Drosophila melanogaster.

In the fly Drosophila melanogaster, neuronal plasticity of synaptic terminals in the first optic neuropil, or lamina, depends on early visual experience within a critical period after eclosion. The current study revealed two additional and parallel mechanisms involved in this type of synaptic terminal plasticity. First, an endogenous circadian rhythm causes daily oscillations in the volume of photoreceptor cell terminals.

The hangover gene negatively regulates bouton addition at the Drosophila neuromuscular junction.

The synaptic growth of neurons during the development and adult life of an animal is a very dynamic and highly regulated process. During larval development in Drosophila new boutons and branches are added at the glutamatergic neuromuscular junction (NMJ) until a balance between neuronal activity and morphological structures is reached. Analysis of several Drosophila mutants suggest that bouton number and size might be regulated by separate signaling processes [Budnik, V.

Requirement of B2-type cyclin-dependent kinases for meristem integrity in Arabidopsis thaliana.

To maintain proper meristem function, cell division and differentiation must be coordinately regulated in distinct subdomains of the meristem. Although a number of regulators necessary for the correct organization of the shoot apical meristem (SAM) have been identified, it is still largely unknown how their function is integrated with the cell cycle machinery to translate domain identity into correct cellular behavior. We show here that the cyclin-dependent kinases CDKB2;1 and CDKB2;2 are required both for normal cell cycle progression and for meristem organization.

Glutamatergic synapses of Drosophila neuromuscular junctions: a high-resolution model for the analysis of experience-dependent potentiation.

The glutamatergic synapses of developing neuromuscular junctions (NMJ) of Drosophila larvae are readily accessible, morphologically simple, and physiologically well-characterized. They therefore have a long and highly successful tradition as a model system for the discovery of genetic and molecular mechanisms of target recognition, synaptogenesis, NMJ development, and synaptic plasticity. However, since the development and the activity-dependent refinement of NMJs are concurrent processes, they cannot easily be separated by the widely applied genetic manipulations that mostly have chronic effects.

Experience-dependent formation and recruitment of large vesicles from reserve pool.

The sizes and contents of transmitter-filled vesicles have been shown to vary depending on experimental manipulations resulting in altered quantal sizes. However, whether such a presynaptic regulation of quantal size can be induced under physiological conditions as a potential alternative mechanism to alter the strength of synaptic transmission is unknown. Here we show that presynaptic vesicles of glutamatergic synapses of Drosophila neuromuscular junctions increase in size as a result of high natural crawling activities of larvae, leading to larger quantal sizes and enhanced evoked synaptic transmission.

Experience-dependent strengthening of Drosophila neuromuscular junctions.

The genetic analysis of larval neuromuscular junctions (NMJs) of Drosophila has provided detailed insights into molecular mechanisms that control the morphological and physiological development of these glutamatergic synapses. However, because of the chronic defects caused by mutations, a time-resolved analysis of these mechanisms and their functional relationships has been difficult so far. In this study we provide a first temporal map of some of the molecular and cellular key processes, which are triggered in wild-type animals by natural larval locomotor activity and then mediate experience-dependent strengthening of larval NMJs.

Differential regulation of active zone density during long-term strengthening of Drosophila neuromuscular junctions.

In this study we established a transgenic Ca2+ imaging technique in Drosophila that enabled us to target the Ca2+ sensor protein yellow Cameleon-2 specifically to larval neurons. This noninvasive method allowed us to measure evoked Ca2+ signals in presynaptic terminals of larval neuromuscular junctions (NMJs). We combined transgenic Ca2+ imaging with electrophysiological recordings and morphological examinations of larval NMJs to analyze the mechanisms underlying persistently enhanced evoked vesicle release in two independent mutants.

The postsynaptic glutamate receptor subunit DGluR-IIA mediates long-term plasticity in Drosophila.

The developing neuromuscular junctions (NMJs) of Drosophila larvae can undergo long-term strengthening of signal transmission, a process that has been shown recently to involve local subsynaptic protein synthesis and that is associated with an elevated synaptic accumulation of the postsynaptic glutamate receptor subunit DGluR-IIA. To analyze the role of altered postsynaptic glutamate receptor expression during this form of genetically induced junctional plasticity, we manipulated the expression levels of two so far-described postsynaptic receptor subunit genes, dglur-IIA and dglur-IIB, in wild-type animals and plasticity mutants. Here we show that elevated synaptic expression of DGluR-IIA, which was achieved by direct transgenic overexpression, by genetically increased subsynaptic protein synthesis, or by a reduced dglur-IIB gene copy number, results in an increased recruitment of active zones, a corresponding enhancement in the strength of junctional signal transmission, and a correlated addition of boutons to the NMJ.