Re: Imaging and reporting considerations for suspected physical abuse (non-accidental injury) in infants and young children. Part 1: initial considerations and appendicular skeleton. A reply

Correspondenc

Zebrafish con/disp1 reveals multiple spatiotemporal requirements for Hedgehog-signaling in craniofacial development

<p>Abstract</p> <p>Background</p> <p>The vertebrate head skeleton is derived largely from cranial neural crest cells (CNCC). Genetic studies in zebrafish and mice have established that the Hedgehog (Hh)-signaling pathway plays a critical role in craniofacial development, partly due to the pathway's role in CNCC development. Disruption of the Hh-signaling pathway in humans can lead to the spectral disorder of Holoprosencephaly (HPE), which is often characterized by a variety of craniofacial defects including midline facial clefting and cyclopia <abbrgrp><abbr bid="B1">1</abbr><abbr bid="B2">2</abbr></abbrgrp>. Previous work has uncovered a role for Hh-signaling in zebrafish dorsal neurocranium patterning and chondrogenesis, however Hh-signaling mutants have not been described with respect to the ventral pharyngeal arch (PA) skeleton. Lipid-modified Hh-ligands require the transmembrane-spanning receptor Dispatched 1 (Disp1) for proper secretion from Hh-synthesizing cells to the extracellular field where they act on target cells. Here we study <it>chameleon </it>mutants, lacking a functional <it>disp1</it>(<it>con/disp1</it>).</p> <p>Results</p> <p><it>con/disp1 </it>mutants display reduced and dysmorphic mandibular and hyoid arch cartilages and lack all ceratobranchial cartilage elements. CNCC specification and migration into the PA primorida occurs normally in <it>con/disp1 </it>mutants, however <it>disp1 </it>is necessary for post-migratory CNCC patterning and differentiation. We show that <it>disp1 </it>is required for post-migratory CNCC to become properly patterned within the first arch, while the gene is dispensable for CNCC condensation and patterning in more posterior arches. Upon residing in well-formed pharyngeal epithelium, neural crest condensations in the posterior PA fail to maintain expression of two transcription factors essential for chondrogenesis, <it>sox9a </it>and <it>dlx2a</it>, yet continue to robustly express other neural crest markers. Histology reveals that posterior arch residing-CNCC differentiate into fibrous-connective tissue, rather than becoming chondrocytes. Treatments with Cyclopamine, to inhibit Hh-signaling at different developmental stages, show that Hh-signaling is required during gastrulation for normal patterning of CNCC in the first PA, and then during the late pharyngula stage, to promote CNCC chondrogenesis within the posterior arches. Further, loss of <it>disp1 </it>disrupted normal expression of <it>bapx1 </it>and <it>gdf5</it>, markers of jaw joint patterning, thus resulting in jaw joint defects in <it>con/disp1 </it>mutant animals.</p> <p>Conclusion</p> <p>This study reveals novel requirements for Hh-signaling in the zebrafish PA skeleton and highlights the functional diversity and differential sensitivity of craniofacial tissues to Hh-signaling throughout the face, a finding that may help to explain the spectrum of human facial phenotypes characteristic of HPE.</p

Keratan sulphate in the tumour environment

Keratan sulphate (KS) is a bioactive glycosaminoglycan (GAG) of some complexity composed of the repeat disaccharide D-galactose β1→4 glycosidically linked to N-acetyl glucosamine. During the biosynthesis of KS, a family of glycosyltransferase and sulphotransferase enzymes act sequentially and in a coordinated fashion to add D-galactose (D-Gal) then N-acetyl glucosamine (GlcNAc) to a GlcNAc acceptor residue at the reducing terminus of a nascent KS chain to effect chain elongation. D-Gal and GlcNAc can both undergo sulphation at C6 but this occurs more frequently on GlcNAc than D-Gal. Sulphation along the developing KS chain is not uniform and contains regions of variable length where no sulphation occurs, regions which are monosulphated mainly on GlcNAc and further regions of high sulphation where both of the repeat disaccharides are sulphated. Each of these respective regions in the KS chain can be of variable length leading to KS complexity in terms of chain length and charge localization along the KS chain. Like other GAGs, it is these variably sulphated regions in KS which define its interactive properties with ligands such as growth factors, morphogens and cytokines and which determine the functional properties of tissues containing KS. Further adding to KS complexity is the identification of three different linkage structures in KS to asparagine (N-linked) or to threonine or serine residues (O-linked) in proteoglycan core proteins which has allowed the categorization of KS into three types, namely KS-I (corneal KS, N-linked), KS-II (skeletal KS, O-linked) or KS-III (brain KS, O-linked). KS-I to -III are also subject to variable addition of L-fucose and sialic acid groups. Furthermore, the GlcNAc residues of some members of the mucin-like glycoprotein family can also act as acceptor molecules for the addition of D-Gal and GlcNAc residues which can also be sulphated leading to small low sulphation glycoforms of KS. These differ from the more heavily sulphated KS chains found on proteoglycans. Like other GAGs, KS has evolved molecular recognition and information transfer properties over hundreds of millions of years of vertebrate and invertebrate evolution which equips them with cell mediatory properties in normal cellular processes and in aberrant pathological situations such as in tumourogenesis. Two KS-proteoglycans in particular, podocalyxin and lumican, are cell membrane, intracellular or stromal tissue–associated components with roles in the promotion or regulation of tumour development, mucin-like KS glycoproteins may also contribute to tumourogenesis. A greater understanding of the biology of KS may allow better methodology to be developed to more effectively combat tumourogenic processes

Increase of Yield, Lycopene, and Lutein Content in Tomatoes Grown Under Continuous PAR Spectrum LED Lighting

Light emitting diodes (LEDs) are an energy efficient alternative to high-pressure sodium (HPS) lighting in tomato cultivation. In the past years, we have learned a lot about the effect of red and blue LEDs on plant growth and yield of tomatoes. From previous studies, we know that plants absorb and utilize most of the visible spectrum for photosynthesis. This part of the spectrum is referred to as the photosynthetically active radiation (PAR). We designed a LED fixture with an emission spectrum that partially matches the range of 400 to 700 nm and thus partially covers the absorption spectrum of photosynthetic pigments in tomato leaves. Tomato plants grown under this fixture were significantly taller and produced a higher fruit yield (14%) than plants grown under HPS lighting. There was no difference in the number of leaves and trusses, leaf area, stem diameter, the electron transport rate, and the normalized difference vegetation index. Lycopene and lutein contents in tomatoes were 18% and 142% higher when they were exposed to the LED fixture. However, the ß-carotene content was not different between the light treatments. Transpiration rate under LED was significantly lower (40%), while the light use efficiency (LUE) was significantly higher (19%) compared to HPS lighting. These data show that an LED fixture with an emission spectrum covering the entire PAR range can improve LUE, yields, and content of secondary metabolites in tomatoes compared to HPS lighting.Peer Reviewe

LED versus HPS Lighting: Effects on Water and Energy Consumption and Yield Quality in Lettuce Greenhouse Production

High-pressure sodium (HPS) lighting is increasingly replaced by LED lighting in lettuce greenhouse cultivation. In contrast to HPS lighting, LEDs do not heat radiation. Therefore, the leaf temperature is significantly lower under LEDs. This raises the question of whether LED lighting has a positive impact on the reduction in water consumption during lettuce production. In this paper, we investigated this question and found that the water consumption of lettuce produced under LEDs was significantly lower (−15%) than under HPS without loss of yield. We also found that supplementary lighting increases the concentrations of caffeoylquinic acid, dicaffeoyltartaric acid, dicaffeoylquinic acid and that of the total phenolic compounds in lettuce leaves by 61%, 39%, 163% and 38%, respectively. Only the LED fixture was also efficient enough to increase the concentration of caffeoyltartaric acid (+24%). Most of the phenolic compounds showed a very strong positive correlation with the chlorophyll concentration in lettuce, which predominated in the leaves exposed to the LED lighting. Based on these facts, we conclude that by optimizing the light composition, more sustainable plant production, higher concentrations of chlorophyll and some phenolic compounds are possible.Bundesministerium für Bildung und ForschungPeer Reviewe