A novel function of CREG in metabolic disorders

Metabolic disorders are public health problems that require prevention and new efficient drugs for treatment. Cellular repressor of E1A-stimulated genes (CREG) is ubiquitously expressed in mature tissues and cells in mammals and plays a critical role in keeping cells or tissues in a mature, homeostatic state. Recently, CREG turns to be an important mediator in the development of metabolic disorders. Here in this review, we briefly discuss the structure and molecular regulation of CREG along with the therapeutic strategy to combat the metabolic disorders.

Clinical Significance and Regulation of ERK5 Expression and Function in Cancer

Extracellular signal-regulated kinase 5 (ERK5) is a unique kinase among MAPKs family members, given its large structure characterized by the presence of a unique C-terminal domain. Despite increasing data demonstrating the relevance of the ERK5 pathway in the growth, survival, and differentiation of normal cells, ERK5 has recently attracted the attention of several research groups given its relevance in inflammatory disorders and cancer. Accumulating evidence reported its role in tumor initiation and progression. In this review, we explore the gene expression profile of ERK5 among cancers correlated with its clinical impact, as well as the prognostic value of ERK5 and pERK5 expression levels in tumors. We also summarize the importance of ERK5 in the maintenance of a cancer stem-like phenotype and explore the major known contributions of ERK5 in the tumor-associated microenvironment. Moreover, although several questions are still open concerning ERK5 molecular regulation, different ERK5 isoforms derived from the alternative splicing process are also described, highlighting the potential clinical relevance of targeting ERK5 pathways.

Regeneration of duckweed (Lemna turonifera) involves genetic molecular regulation and cyclohexane release

Plant regeneration is important for vegetative propagation, detoxification and the obtain of transgenic plant. We found that duckweed regeneration could be enhanced by regenerating callus. However, very little is known about the molecular mechanism and the release of volatile organic compounds (VOCs). To gain a global view of genes differently expression profiles in callus and regenerating callus, genetic transcript regulation has been studied. Auxin related genes have been significantly down-regulated in regenerating callus. Cytokinin signal pathway genes have been up-regulated in regenerating callus. This result suggests the modify of auxin and cytokinin balance determines the regenerating callus. Volatile organic compounds release has been analysised by gas chromatography/ mass spectrum during the stage of plant regeneration, and 11 kinds of unique volatile organic compounds in the regenerating callus were increased. Cyclohexane treatment enhanced duckweed regeneration by initiating root. Moreover, Auxin signal pathway genes were down-regulated in callus treated by cyclohexane. All together, these results indicated that cyclohexane released by regenerating callus promoted duckweed regeneration. Our results provide novel mechanistic insights into how regenerating callus promotes regeneration.

Dermal White Adipose Tissue (dWAT) Is Regulated by Foxn1 and Hif-1α during the Early Phase of Skin Wound Healing

Dermal white adipose tissue (dWAT) is involved in the maintenance of skin homeostasis. However, the studies concerning its molecular regulation are limited. In the present paper, we ask whether the introduction of two transcription factors, Foxn1 and Hif-1α, into the post-wounded skin of Foxn1-/- mice regulates dWAT during wound healing (days 3 and 6). We have chosen lentivirus vectors (LVs) as a tool to deliver Foxn1 and Hif-1α into the post-wounded skin. We documented that combinations of both transgenes reduces the number, size and diameter of dermal adipocytes at the wound bed area. The qRT-PCR analysis of pro-adipogenic genes, revealed that LV-Hif-1α alone, or combined with LV-Foxn1, increases the mRNA expression of Pparγ, Glut 4 and Fasn at post-wounding day 6. However, the most spectacular stimulatory effect of Foxn1 and/or Hif-1α was observed for Igf2, the growth factor participating in adipogenic signal transduction. Our data also shows that Foxn1/Hif-1α, at post-wounding day 3, reduces levels of CD68 and MIP-1γ mRNA expression and the percentage of CD68 positive cells in the wound site. In conclusion, the present data are the first to document that Foxn1 and Hif-1α cooperatively (1) regulate dWAT during the proliferative phase of skin wound healing through the Igf2 signaling pathway, and (2) reduce the macrophages content in the wound site.

Adapting CRISPR/Cas9 Lentivirus Technology for Functional Studies of GATA6 & GATA4 during Bovine Preimplantation Embryogenesis

<p>In recent times, cattle embryology has been under the spotlight of investigation due to its apparent economic values. This is especially relevant in the case of New Zealand, owing to its high percentage of livestock export. Specifically, the period of peri-implantation development has been of particular relevance. During this stage, the developing zygote will establish 3 key lineages – epiblast, hypoblast and trophoblast. Previous studies have elucidated that a significant number of embryos die prior to implantation, therefore highlighting the importance of correctly establishing these 3 lineages to overall embryonic survival. However, while embryological stages of the preimplantation embryo have been extensively studied in their eutherian cousin, mice, the molecular regulation of that of cattle remains much less addressed. Whereas the regulation of bovine embryo development is orchestrated by many transcriptional regulators, or genetic regulatory networks (GNP), we aimed to focus our studies on 2 key transcriptional regulators, GATA4 and GATA6. During early embryogenesis, both these transcriptional factors are known molecular regulators that drive the establishment of the hypoblast lineage in mice. By and large, while their respective expression has been documented in cattle embryos, functional studies towards these markers have not yet been performed. Latest advances in molecular biology have given us novel methods to study the mechanism of bovine embryogenesis. To this end, the continuing perfection of CRISPR technologies in the last decade - in particular its delivery through lentiviral vectors, has established an ability to generate stable, targeted knock-out mutants. Therefore, it is aimed in this thesis to design and test lentiviral particles that induce knock-out mutants of GATA4 and GATAT6, to test their efficacy in primary cell cultures (bovine cumulus cells) and to functionally analyse the effect of GATA4 and GATA6 knockdowns in early bovine embryos.</p>

Adapting CRISPR/Cas9 Lentivirus Technology for Functional Studies of GATA6 & GATA4 during Bovine Preimplantation Embryogenesis

<p>In recent times, cattle embryology has been under the spotlight of investigation due to its apparent economic values. This is especially relevant in the case of New Zealand, owing to its high percentage of livestock export. Specifically, the period of peri-implantation development has been of particular relevance. During this stage, the developing zygote will establish 3 key lineages – epiblast, hypoblast and trophoblast. Previous studies have elucidated that a significant number of embryos die prior to implantation, therefore highlighting the importance of correctly establishing these 3 lineages to overall embryonic survival. However, while embryological stages of the preimplantation embryo have been extensively studied in their eutherian cousin, mice, the molecular regulation of that of cattle remains much less addressed. Whereas the regulation of bovine embryo development is orchestrated by many transcriptional regulators, or genetic regulatory networks (GNP), we aimed to focus our studies on 2 key transcriptional regulators, GATA4 and GATA6. During early embryogenesis, both these transcriptional factors are known molecular regulators that drive the establishment of the hypoblast lineage in mice. By and large, while their respective expression has been documented in cattle embryos, functional studies towards these markers have not yet been performed. Latest advances in molecular biology have given us novel methods to study the mechanism of bovine embryogenesis. To this end, the continuing perfection of CRISPR technologies in the last decade - in particular its delivery through lentiviral vectors, has established an ability to generate stable, targeted knock-out mutants. Therefore, it is aimed in this thesis to design and test lentiviral particles that induce knock-out mutants of GATA4 and GATAT6, to test their efficacy in primary cell cultures (bovine cumulus cells) and to functionally analyse the effect of GATA4 and GATA6 knockdowns in early bovine embryos.</p>

Analysis of Wheat Wax Regulation Mechanism by Liposome and Transcriptome

As a barrier for plants to contact with the outside world, epidermal wax plays an important role in resisting biotic and abiotic stresses. In this study, we analyzed the effect of wax content on leaf permeability by measuring the wax loss rate in the leaf. To further clarify the wax composition of the wheat epidermis and its molecular regulation mechanism, we applied untargeted lipidomic and transcriptome analysis on the leaf epidermis wax of Jimai 22 low-wax mutant (waxless) and multi-wax mutant (waxy). Our research showed that the mutant waxy has a slow loss rate, which can maintain higher leaf water content. 31 lipid subclasses and 1,367 lipid molecules were identified. By analyzing the wax differences of the two mutants, we found that the main lipid components of leaf epidermis wax in Jimai 22 were WE (C19-C50), DG (C27-C53), MG (C31-C35), and OAHFA (C31-C52). Carbon chain length analysis showed that, in wheat epidermis wax, WE was dominated by C44 molecules, DG was mainly concentrated in C47, C45, C37, and C31 molecules, C48 played a leading role in OAHFA, and C35 and C31 played a major role in MG. Among them, DG, MG, and OAHFA were detected in wheat leaf wax for the first time, and they were closely related to stress resistance. Compared with the waxy, 6,840 DEGs were detected in the mutant waxless, 3,181 DEGs were upregulated, and 3,659 DEGs were downregulated. The metabolic pattern of main waxy components in the wheat epidermis was constructed according to KEGG metabolic pathway and 46 related genes were screened, including KSC, TER, FAR, WSD1, CER1, MAH1, ALDH7A1, CYP704B1, ACOT1_2_4, CYP86, MGLL, GPAT, ALDH, DPP1, dgkA, plsC, and E2.3.1.158 related genes. The screened wax-related genes were confirmed to be highly reliable by qRT-PCR. In addition, we found TER gene TraesCS6B03G1132900LC in wheat mutant waxless leaves for the first time, which inhibited the synthesis of long-chain acyl-CoA (n+2) by downregulating its expression. These results provide valuable reference information for further study of wheat epidermis wax heredity and molecular regulation.

Targeted therapy of irritable bowel syndrome with anti-inflammatory cytokines

Irritable bowel syndrome (IBS) is a multifactorial disease of which infection, as well as inflammation, has recently been considered as an important cause. Inflammation works as a potential pathway for the pathogenesis of IBS. In this review, we have discussed the targeted therapy of IBS. We used the search term “inflammation in IBS” and “proinflammatory” and “antiinflammatory cytokines and IBS” using PubMed, MEDLINE, and Google Scholar. The literature search included only articles written in the English language. We have also reviewed currently available anti-inflammatory treatment and future perspectives. Cytokine imbalance in the systematic circulation and the intestinal mucosa may also characterize IBS presentation. Imbalances of pro-and anti-inflammatory cytokines and polymorphisms in cytokine genes have been reported in IBS. The story of targeted therapy of IBS with anti-inflammatory cytokines is far from complete and it seems that it has only just begun. This review describes the key issues related to pro-inflammatory cytokines associated with IBS, molecular regulation of immune response in IBS, inhibitors of pro-inflammatory cytokines in IBS, and clinical perspectives of pro- and anti-inflammatory cytokines in IBS.

Hedgehog signaling controls mouth opening in the amphioxus

Introduction The left-sided position of the mouth in amphioxus larvae has fascinated researchers for a long time. Despite the fundamental importance of mouth development in the amphioxus, the molecular regulation of its development is almost unknown. In our previous study, we showed that Hh mutation in the amphioxus leads to no mouth opening, indicating a requirement of Hh signaling for amphioxus mouth formation. Nevertheless, since the Hh mutant also exhibits defects in early left-right (LR) patterning, it remains currently unknown whether the loss of mouth opening is affected directly by Hh deficiency or a secondary effect of its influence on LR establishment. Results We demonstrated that knockout of the Smo gene, another key component of the Hh signaling pathway, in the amphioxus resulted in the absence of mouth opening, but caused no effects on LR asymmetry development. Upregulation of Hh signaling led to a dramatic increase in mouth size. The inability of Smo mutation to affect LR development is due to Smo’s high maternal expression in amphioxus eggs and cleavage-stage embryos. In Smo mutants, Pou4 and Pax2/5/8 expression at the primordial oral site is not altered before mouth opening. Conclusions Based on these results and our previous study, we conclude that Hh signal is necessary for amphioxus mouth formation and that the Hh-mediated regulation of mouth development is specific to the mouth. Our data suggest that Hh signaling regulates mouth formation in the amphioxus in a similar way as that in vertebrates, indicating the conserved role of Hh signaling in mouth formation.