An intron SNP rs2069837 in IL-6 is associated with osteonecrosis of the femoral head development

Background Genetic polymorphisms play a crucial role in the development of osteonecrosis of the femoral head (ONFH). This study mainly explored the association of IL-6 variants and ONFH susceptibility among the Chinese Han population. Methods Two variants (rs2069837, and rs13306435) in the IL-6 gene were identified and genotyped from 566 patients with ONFH and 566 healthy controls. The associations between IL-6 polymorphisms and ONFH susceptibility were assessed using odds ratio (OR) and 95% confidence interval (95% CI) via logistic regression. The potential function of these two variants was predicted by the HaploReg online database. Results The results of the overall analysis revealed that IL-6 rs2069837 was correlated with decreased risk of ONFH among the Chinese Han population (p < 0.05). In stratified analysis, rs2069837 also reduced the susceptibility to ONFH in older people (> 51 years), males, nonsmokers, and nondrinkers (p < 0.05). However, no associations between rs13306435 and ONFH susceptibility were observed (p > 0.05). Conclusions To sum up, we suggested that rs2069837 G>A polymorphism in the IL-6 gene was significantly associated with a decreased risk of ONFH among the Chinese Hans. These findings underscored the crucial role of IL-6 rs2069837 in the occurrence of ONFH.

T-Cell Factors as Transcriptional Inhibitors: Activities and Regulations in Vertebrate Head Development

Since its first discovery in the late 90s, Wnt canonical signaling has been demonstrated to affect a large variety of neural developmental processes, including, but not limited to, embryonic axis formation, neural proliferation, fate determination, and maintenance of neural stem cells. For decades, studies have focused on the mechanisms controlling the activity of β-catenin, the sole mediator of Wnt transcriptional response. More recently, the spotlight of research is directed towards the last cascade component, the T-cell factor (TCF)/Lymphoid-Enhancer binding Factor (LEF), and more specifically, the TCF/LEF-mediated switch from transcriptional activation to repression, which in both embryonic blastomeres and mouse embryonic stem cells pushes the balance from pluri/multipotency towards differentiation. It has been long known that Groucho/Transducin-Like Enhancer of split (Gro/TLE) is the main co-repressor partner of TCF/LEF. More recently, other TCF/LEF-interacting partners have been identified, including the pro-neural BarH-Like 2 (BARHL2), which belongs to the evolutionary highly conserved family of homeodomain-containing transcription factors. This review describes the activities and regulatory modes of TCF/LEF as transcriptional repressors, with a specific focus on the functions of Barhl2 in vertebrate brain development. Specific attention is given to the transcriptional events leading to formation of the Organizer, as well as the roles and regulations of Wnt/β-catenin pathway in growth of the caudal forebrain. We present TCF/LEF activities in both embryonic and neural stem cells and discuss how alterations of this pathway could lead to tumors.

Panarthropod tiptop/teashirt and spalt orthologs and their potential role as “trunk”-selector genes

Background In the vinegar fly Drosophila melanogaster, the homeodomain containing transcription factor Teashirt (Tsh) appears to specify trunk identity in concert with the function of the Hox genes. While in Drosophila there is a second gene closely related to tsh, called tiptop (tio), in other arthropods species only one copy exists (called tio/tsh). The expression of tsh and tio/tsh, respectively, is surprisingly similar among arthropods suggesting that its function as trunk selector gene may be conserved. Other research, for example on the beetle Tribolium castaneum, questions even conservation of Tsh function among insects. The zinc-finger transcription factor Spalt (Sal) is involved in the regulation of Drosophila tsh, but this regulatory interaction does not appear to be conserved in Tribolium either. Whether the function and interaction of tsh and sal as potential trunk-specifiers, however, is conserved is still unclear because comparative studies on sal expression (except for Tribolium) are lacking, and functional data are (if at all existing) restricted to Insecta. Results Here, we provide additional data on arthropod tsh expression, show the first data on onychophoran tio/tsh expression, and provide a comprehensive investigation on sal expression patterns in arthropods and an onychophoran. Conclusions Our data support the idea that tio/tsh genes are involved in the development of “trunk” segments by regulating limb development. Our data suggest further that the function of Sal is indeed unlikely to be conserved in trunk vs head development like in Drosophila, but early expression of sal is in line with a potential homeotic function, at least in Arthropoda.

Determination of Aquaponic Water Macronutrient Concentrations Based on Lactuca Sativa Leaf Photosynthetic Signatures using Hybrid Gravitational Search and Recurrent Neural Network

Crop quality depends dominantly on the nutrients present in its growth media. For precision farming, fertigation is a challenge, especially when dealing with economical and efficiency factors. In this study, the aquaponic pond water macronutrient prediction model (wNPK) was developed based on leaf photosynthetic signature predictors. Aquaphotomics was preliminarily used for correlating physical limnological properties with nitrate, phosphate, potassium concentrations, and the leaf signatures. Using a digital camera, 18 spectro-textural-morphological features were extracted. Neighborhood component analysis (NCA) and ReliefF algorithms selected the spectral components blue, a*, and red minus luma as the most significant as supported by principal component analysis, resulting in low computational cost. A Gravitational Search Algorithm (GSA) was employed to optimize the recurrent neural network (RNN) architecture resulting in higher sensitivity. The hybrid NCA-ReliefF-GSA-RNN (wNPK) predicted NPK with 93.61, 84.03, and 91.39 % accuracy, respectively, besting out other configured feature-based machine learning models. Using wNPK, it was confirmed that potassium helped in accelerating seed germination and nitrogen in promoting chlorophyll intensification, especially on the 6th week after sowing. Phosphate and potassium were the energy and health elements that were consumed in a larger amount at the end of the head development stage. wNPK rules out that macronutrient concentration have a direct resemblance to crop leaf signatures; thus, a leaf is a good indicator of the water quality. The results pointed out that the use of a single camera to measure both water macronutrient concentrations and crop signature at the same time is an innovative, efficient, and economical approach for precision farming.Highlights Aquaponic pond water nutrient estimation based on leaf photosynthetic signatures Macronutrient biomarker extraction through UV-Vis-NIR aquaphotomics Highly accurate macronutrient prediction using hybrid gravitational search and RNN Potassium promotes seed germination and nitrogen in chlorophyll intensification Phosphate and potassium are consumed in greater scale during head development Graphical abstract

Wnt Signaling Drives Correlated Changes in Facial Morphology and Brain Shape

Canonical Wnt signaling plays multiple roles critical to normal craniofacial development while its dysregulation is known to be involved in structural birth defects of the face. However, when and how Wnt signaling influences phenotypic variation, including those associated with disease, remains unclear. One potential mechanism is via Wnt signaling’s role in the patterning of an early facial signaling center, the frontonasal ectodermal zone (FEZ), and its subsequent regulation of early facial morphogenesis. For example, Wnt signaling may directly alter the shape and/or magnitude of expression of the sonic hedgehog (SHH) domain in the FEZ. To test this idea, we used a replication-competent avian sarcoma retrovirus (RCAS) encoding Wnt3a to modulate its expression in the facial mesenchyme. We then quantified and compared ontogenetic changes in treated to untreated embryos in the three-dimensional (3D) shape of both the SHH expression domain of the FEZ, and the morphology of the facial primordia and brain using iodine-contrast microcomputed tomography imaging and 3D geometric morphometrics (3DGM). We found that increased Wnt3a expression in early stages of head development produces correlated variation in shape between both structural and signaling levels of analysis. In addition, altered Wnt3a activation disrupted the integration between the forebrain and other neural tube derivatives. These results show that activation of Wnt signaling influences facial shape through its impact on the forebrain and SHH expression in the FEZ, and highlights the close relationship between morphogenesis of the forebrain and midface.

Copper signaling promotes proteostasis and animal development via allosteric activation of ubiquitin E2D conjugases

SummaryFine-tunning of ubiquitin-conjugating enzymes (E2s), which orchestrate posttranslational modifications that control protein and cell fate, remains largely elusive. Recently, copper signaling emerged as a critical regulator of cell growth and neuronal differentiation, yet confluence of these key pathways has not been reported. Here we show that subtle rises in cellular copper strikingly increase polyubiquitination in numerous mammalian cell lines, while markedly accelerating protein degradation. Using biochemistry, proteomics, NMR spectroscopy and mutational analyses, we link Cu+-enhanced protein ubiquitination and degradation to an evolutionarily conserved CXXXC motif in the E2D (UBE2D) clade. Cu+ binding to this sub-femtomolar-affinity site induces allosteric changes that transduce to the active site region and increase enzyme activity. This machinery couples physiologic fluctuations in cytoplasmic Cu+ with the degradation rate of numerous proteins including the canonical substrate, p53. In Drosophila harboring a larval-lethal UbcD1 knockdown, human E2D2 expression supported near-normal development but ablation of its Cu+ binding site profoundly disrupted head development. Our findings introduce Cu+ as a novel regulator of E2D activity through an allosteric switch whose emergence coincided with animal multicellularity. Through this unexpected signaling mechanism, crosstalk between copper and protein ubiquitination could have broad impact including upon neurobiological development and cell cycling.One Sentence SummaryConserved allostery of ubiquitin E2D conjugases links sub-fM copper signaling to protein degradation and animal morphogenesis.

Craniofacial transitions: the role of EMT and MET during head development

ABSTRACTWithin the developing head, tissues undergo cell-fate transitions to shape the forming structures. This starts with the neural crest, which undergoes epithelial-to-mesenchymal transition (EMT) to form, amongst other tissues, many of the skeletal tissues of the head. In the eye and ear, these neural crest cells then transform back into an epithelium, via mesenchymal-to-epithelial transition (MET), highlighting the flexibility of this population. Elsewhere in the head, the epithelium loses its integrity and transforms into mesenchyme. Here, we review these craniofacial transitions, looking at why they happen, the factors that trigger them, and the cell and molecular changes they involve. We also discuss the consequences of aberrant EMT and MET in the head.

Dynamic Changes of the Anthocyanin Biosynthesis Mechanism During the Development of Heading Chinese Cabbage (Brassica rapa L.) and Arabidopsis Under the Control of BrMYB2

Chinese cabbage is an important vegetable mainly planted in Asian countries, and mining the molecular mechanism responsible for purple coloration in Brassica crops is fast becoming a research hotspot. In particular, the anthocyanin accumulation characteristic of purple heading Chinese cabbage, along with the plant’s growth and head developing, is still largely unknown. To elucidate the dynamic anthocyanin biosynthesis mechanism of Chinese cabbage during its development processes, here we investigated the expression profiles of 86 anthocyanin biosynthesis genes and corresponding anthocyanin accumulation characteristics of plants as they grew and their heads developed, between purple heading Chinese cabbage 11S91 and its breeding parents. Anthocyanin accumulation of 11S91 increased from the early head formation period onward, whereas the purple trait donor 95T2-5 constantly accumulated anthocyanin throughout its whole plant development. Increasing expression levels of BrMYB2 and BrTT8 together with the downregulation of BrMYBL2.1, BrMYBL2.2, and BrLBD39.1 occurred in both 11S91 and 95T2-5 plants during their growth, accompanied by the significantly continuous upregulation of a phenylpropanoid metabolic gene, BrPAL3.1; a series of early biosynthesis genes, such as BrCHSs, BrCHIs, BrF3Hs, and BrF3’H; as well as some key late biosynthesis genes, such as BrDFR1, BrANS1, BrUF3GT2, BrUF5GT, Br5MAT, and Brp-Cout; in addition to the transport genes BrGST1 and BrGST2. Dynamic expression profiles of these upregulated genes correlated well with the total anthocyanin contents during the processes of plant growth and leaf head development, and results supported by similar evidence for structural genes were also found in the BrMYB2 transgenic Arabidopsis. After intersubspecific hybridization breeding, the purple interior heading leaves of 11S91 inherited the partial purple phenotypes from 95T2-5 while the phenotypes of seedlings and heads were mainly acquired from white 94S17; comparatively in expression patterns of investigated anthocyanin biosynthesis genes, cotyledons of 11S91 might inherit the majority of genetic information from the white type parent, whereas the growth seedlings and developing heading tissues of 11S91 featured expression patterns of these genes more similar to 95T2-5. This comprehensive set of results provides new evidence for a better understanding of the anthocyanin biosynthesis mechanism and future breeding of new purple Brassica vegetables.

Comparative between Syndromic and Nonsyndromic Craniosynostosis: A Literature Review

Craniosynostosis (CS) refers to the premature fusion in the perinatal stage of one or multiple skull sutures, also denominated synostoses (sagittal, metopic, uni and bilateral coronal, and lamboidal), which are commonly accompanied by facial, trunk, and limb deformities. During normal human body and head development, cranial growth achieves approximately 80% of the adult size at birth and its definitive size between 2.5 and 3 years of age. In the fetal or newborn skull, the flat bones are separated by four fontanelles and six major cranial sutures that participate in this process. Hereby presented the literature review of syndromic and non-syndromic craniosynostosis.