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The role of retinoic acid in regulating muscle development in zebrafish embryos through Fgf8 signalling is studied.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2004.03.033 Byline: G. Begemann, M. Marx, K. Mebus, A. Meyer, M. Bastmeyer Keywords: Retinaldehyde dehydrogenase; raldh2; Retinoic acid; Hindbrain patterning; Cranial motor neurons; Zebrafish Abstract: Retinoic acid (RA) has been identified as a key signal involved in the posteriorization of vertebrate neural ectoderm. The main biosynthetic enzyme responsible for RA signaling in the hindbrain and spinal cord is Raldh2. However, neckless/raldh2-mutant (nls) zebrafish exhibit only mild degrees of anteriorization in the neural ectoderm, compared to full vitamin A deficiency in amniotes and the Raldh2.sup.-/- mouse. Here we investigated the role of RA during neuronal development in the zebrafish hindbrain and anterior spinal cord using DEAB, an inhibitor of retinaldehyde dehydrogenases. We show that the nls hindbrain and spinal cord are not fully devoid of RA, since blocking Raldh-mediated RA signaling leads to a more severe hindbrain phenotype than in nls. The anteroposterior distribution of branchiomotor neurons in the facial and more posterior nuclei depends on full RA signaling throughout early and late gastrula stages. In contrast, inhibition of RA synthesis after gastrulation reduces the number of branchiomotor neurons in the vagal nucleus, but has no effect on anteroposterior cell fates. In addition, blockage of RA-mediated signaling not only interferes with the differentiation of branchiomotor neurons and their axons in the hindbrain, but also affects the development of the posterior lateral line nerve. Article History: Received 29 January 2004; Revised 18 March 2004; Accepted 29 March 2004

We report the embryonic phenotype of muscleblind (mbl), a recently described Drosophila gene involved in terminal differentiation of adult ommatidia. mbl is a nuclear protein expressed late in the embryo in pharyngeal, visceral, and somatic muscles, the ventral nerve cord, and the larval photoreceptor system. All three mbl alleles studied exhibit a lethal phenotype and die as stage 17 embryos or first instar larvae. These larvae are partially paralyzed, show a characteristically contracted abdomen, and lack striation of muscles. Our analysis of the somatic musculature shows that the pattern of muscles is established correctly, and they form morphologically normal synapses. Ultrastructural analysis, however, reveals two defects in the terminal differentiation of the muscles: inability to differentiate Z-bands in the sarcomeric apparatus and reduction of extracellular tendon matrix at attachment sites to the epidermis. Failure to differentiate both structures could explain the partial paralysis and contracted abdomen phenotype. Analysis of mbl expression in embryos that are either mutant for Dmef2 or ectopically express Dmef2 places mbl downstream of Dmef2 function in the myogenic differentiation program. mbl, therefore, may act as a critical element in the execution of two Dmef2-dependent processes in the terminal differentiation of muscles. Key Words: muscleblind; Z-bands; muscle attachments; myogenesis; Drosophila.

The retinoblastoma tumor suppressor protein (RB) specifically binds to the protein BRG1 in the yeast two-hybrid system. The Drosophila brahma and the BRG1 have identical sequences, which are similar to the sequence of the SNF2/SWI2, a yeast transcriptional activator. An RB binding motif, similar to that found in viral oncoproteins, constitutes the BRG1. The motif is bound to the A/B pocket.

• Deforestation and forest degradation remain the most prominent challenges in global forest governance. • In a multipolar world, issue specific coalitions across world regions are critical for global forest governance. • Governance initiatives connecting to "high politics" such as trade are promising for global forest governance. • Both investment and informal markets are not sufficiently accounted for in global forest governance. • New information technologies can increase transparency in global forest governance. Deforestation and forest degradation remain huge global environmental challenges. Over the last decades, various forest governance initiatives and institutions have evolved in global response to interlinked topics such as climate change mitigation, biodiversity conservation, indigenous rights, and trade impacts – accompanied by various levels of academic attention. Using a Delphi methodology that draws on both policy and academic insights, we assess the currently perceived state of play in global forest governance and identify possible future directions. Results indicate that state actors are seen to be key in providing supportive regulatory frameworks, yet interviewees do not believe these will be established at the global scale. Rather, respondents point to issue-specific, regional and inter-regional coalitions of the willing, involving the private sector, to innovate global forest governance. Linking forest issues with high politics may hold promise, as demonstrated by initiatives regarding illegal logging and timber trade. Confident rule-setting in support of the public good as well as responsible investments are seen as further avenues. New forest governance "hypes", if used strategically, can provide leverage points and resources to ensure sustainability effects on the ground. At the same time, informal markets are often crucial for governance outcomes and need consideration. As such, clarifying tenure in sovereignty-sensitive ways is important, as are innovative ways for inclusive "glocal" decision-making. Lastly, new technologies, big data and citizens' capacities are identified as potent innovation opportunities, for making global dependencies between consumption, production and deforestation visible and holding players accountable across the value chains. [ABSTRACT FROM AUTHOR]

Steel structures, such as bridges, must be continuously maintained. Due to increasing traffic loads, design and execution shortcomings, many steel bridges are subject to various types of damage, such as cracks. The bridges must be maintained by crack removal and re-welding the cracks. During this work, the bridge is closed for traffic in order to suppress the crack flank movement during welding. As a result, traffic loads on other routes are higher, which increases further damage on detour routes and subsequently additional welding work and costs on these structures. Therefore, the aim is to provide a method that allows welding work on steel structures under running traffic, respectively under cyclic loads. First, measurements at a representative steel bridge were conducted to derive gap opening parameters of amplitude and frequency for welding tests under cyclic loads. In a test setup for reproducible and comparable welding tests, specimen were welded under cyclic loads. Deep grinding of the root layer allowed defect-free welding within the range of 0.1 mm amplitude at a frequency of 2 Hz loadings. For such welds, the weld quality and the fatigue strength was comparable to the standard requirements. • Structural health monitoring was used to measure the gap opening of a typical crack. • Welding under service conditions is under certain aspects possible. • Optically defect-free welds were welded up to a limit of 0.1 mm amplitude. • Unavoidable smaller hot cracks have to remove by deep grinding of the root layer. • Weld seams can be realized with regard to weld quality and fatigue strength. [ABSTRACT FROM AUTHOR]

[Display omitted] Impaired virus clearance in a subgroup of atopic dermatitis (AD) patients can lead to severe herpes simplex virus (HSV) infections called eczema herpeticum (EH). We recently identified a type 2 skewed viral immune response in EH patients. Clinical data suggest a reduced incidence of EH in AD patients treated with dupilumab, although immunologic investigations of this phenomenon are still lacking. We examined the impact of dupilumab on the HSV type 1 (HSV-1) specific immune response in AD, focusing on patients with (ADEH+) and without (ADEH−) a history of EH. Sera and peripheral blood mononuclear cells were collected from ADEH+ and ADEH− patients, a subgroup of whom was receiving dupilumab treatment, and healthy controls. Serum samples were tested for IgE against HSV-1 glycoprotein D (n = 85). Peripheral blood mononuclear cells were stimulated with HSV peptides, and activated CD4+ and CD8+ cells were characterized by flow cytometry after magnetic enrichment via CD154 or CD137 (n = 60). Cytokine production of HSV-1–reactive T-cell lines (n = 33) and MHC-I tetramer+ (HSV-1–UL25) CD8+ T cells was investigated by bead assay and intracellular cytokine staining (n = 21). We confirmed that HSV-1–specific IgE is elevated in ADEH+ patients. During dupilumab treatment, the IgE levels were significantly decreased, reaching levels of healthy controls. HSV-1–specific T C 1 frequencies were elevated in ADEH− patients treated with dupilumab compared to dupilumab-negative patients. There were no changes in the frequencies of HSV-1–specific T H cells while receiving dupilumab therapy. AD patients receiving dupilumab exhibited elevated IFN-γ and reduced IL-4 production in HSV-1–UL25-epitope–specific T cells compared to dupilumab-negative patients. Dupilumab may improve the HSV-1–specific immune response in AD as a result of an increased type I immune response and a reduction of HSV-1–specific IgE. [ABSTRACT FROM AUTHOR]

A novel control concept was developed for a two phase biocatalytic oxidoreduction system. The hydrophobic substrate acetophenone dissolved in n -heptane is reduced to ( S )-1-phenylethanol by Candida parapsilosis carbonyl reductase 2, immobilized in a polyvinyl alcohol hydrogel. The cofactor NADH is regenerated via formic acid oxidation using likewise immobilized Candida boidinii formate dehydrogenase, increasing the pH-value of the aqueous phase. Therefore, the measured amount of CO 2 leaving the reactor is used to calculate the amount of formic acid to be replaced. Experiments lead to unexpectedly poor conversions motivating the development of a holistic process model, which was exclusively based on literature data and did not require parameter fitting. Simulation studies identified the CO 2 -solubility in n -heptane as the root cause for the time-lag in co-substrate feed and the resulting pH-shifts leading to poor conversions. They also indicated enzyme activity and stability as improvement targets, and the choice of an organic phase with low CO 2 -solubility. Exemplarily, increased buffer concentration to stabilize the pH within the hydrogel resulted in a predicted 13% productivity improvement, which could be validated experimentally, thus highlighting the potential of process models for complex biocatalytic process evaluation. [ABSTRACT FROM AUTHOR]

Snacking, i.e., the intake of small amounts of palatable food items, is a common behavior in modern societies, promoting overeating and obesity. Shifting food intake into the daily rest phase disrupts circadian rhythms and is also known to stimulate weight gain. We therefore hypothesized that chronic snacking in the inactive phase may promote body weight gain and that this effect is based on disruption of circadian clocks. Male mice were fed a daily chocolate snack either during their rest or their active phase and body weight development and metabolic parameters were investigated. Snacking experiments were repeated in constant darkness and in clock-deficient mutant mice to examine the role of external and internal time cues in mediating the metabolic effects of snacking. Chronic snacking in the rest phase increased body weight gain and disrupted metabolic circadian rhythms in energy expenditure, body temperature, and locomotor activity. Additionally, these rest phase snacking mice assimilated more energy during the inactive phase. Body weight remained increased in rest phase snacking wildtype mice in constant darkness as well as in clock-deficient mutant mice under a regular light–dark cycle compared to mice snacking in the active phase. Weight gain effects were abolished in clock-deficient mice in constant darkness. Our data suggest that mistimed snacking increases energy resorption and promotes body weight gain. This effect requires a functional circadian clock at least under constant darkness conditions. [Display omitted] • Snack timing determines body weight gain and fat mass in male mice. • Rest phase snacking disturbs daily rhythms in energy expenditure and activity. • Rest phase snacking dampens intestinal clock gene expression rhythms. • Rest phase snacking leads to higher energy resorption. • Timed snack effects require a circadian clock or a rhythmic light–dark cycle. [ABSTRACT FROM AUTHOR]

POLA1 encodes a subunit of the DNA polymerase alpha, a key enzyme for the initiation of DNA synthesis. In males, hemizygous hypomorphic variants in POLA1 have been identified as the cause of X-linked pigmentary reticulate disorder (XLPDR) and a novel X-linked neurodevelopmental disorder termed Van Esch-O'Driscoll syndrome (VEODS), while female carriers have been reported to be healthy. Nullisomy for POLA1 was speculated to be lethal due to its crucial function, while the effect of loss of one allele in females remained unknown. Here, we report on a three-generation family harboring a deletion of POLA1 in females showing subfertility as the only phenotype. Our findings show that heterozygous deletions or truncating variants in females with skewed X inactivation do not cause VEODS and support the hypothesis of very early embryonic lethality in males with POLA1 nullisomy. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents R&D activities in the field of laser-induced breakdown spectroscopy for industrial applications and shows novel LIBS systems running in routine operation for inline process control tasks. Starting with a comparison of the typical characteristics of LIBS with XRF and spark-discharge optical emission spectrometry, the principal structure of LIBS machines embedded for inline process monitoring will be presented. A systematic requirement analysis for LIBS systems following Ishikawa's scheme was worked out. Stability issues are studied for laser sources and Paschen-Runge spectrometers as key components for industrial LIBS systems. Examples of industrial applications range from handheld LIBS systems using a fiber laser source, via a set of LIBS machines for inline process control tasks, such as scrap analysis, coal analysis, liquid slag analysis and finally monitoring of drill dust. [Copyright &y& Elsevier]