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1.
Genome Biol Evol ; 2020 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-32433766

RESUMEN

Lytechinus variegatus is a camarodont sea urchin found widely throughout the western Atlantic Ocean in a variety of shallow-water marine habitats. Its distribution, abundance, and amenability to developmental perturbation make it a popular model for ecologists and developmental biologists. Here, we present a chromosomal-level genome assembly of L. variegatus generated from a combination of PacBio long reads, 10X Genomics sequencing, and HiC chromatin interaction sequencing. We show L. variegatus has 19 chromosomes with an assembly size of 870.4 Mb. The contiguity and completeness of this assembly is reflected by a scaffold length N50 of 45.5Mb and BUSCO completeness score of 95.5%. Ab-initio and transcript-informed gene modelling and annotation identified 27,232 genes with an average gene length of 12.6 Kb, comprising an estimated 39.5% of the genome. Repetitive regions, on the other hand, make up approximately 45.4% of the genome. Physical mapping of well-studied developmental genes onto each chromosome reveals non-random spatial distribution of distinct genes and gene families, which provides insight into how certain gene families may have evolved and are transcriptionally regulated in this species. Lastly, aligning RNA-seq and ATAC-seq data onto this assembly demonstrates the value of highly contiguous, complete genome assemblies for functional genomics analyses that is unattainable with fragmented, incomplete assemblies. This genome will be of great value to the scientific community as a resource for genome evolution, developmental, and ecological studies of this species and the Echinodermata.

2.
Electrophoresis ; 2020 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-32436592

RESUMEN

Dynamic pH barrage junction focusing in capillary electrophoresis (CE) enables effective signal enhancement, quantitative capture efficiencies and straightforward optimization. The method is a technical variant of dynamic pH junction focusing. CE separation with dynamic pH barrage junction focusing is compatible with both optical and mass spectrometric (MS) detection. We developed a CE-MS/MS method using hydrophilic polyethyleneimine (PEI) coated capillaries and validated it for the qualitative analysis of amino acids, peptides and tryptic peptides of digested monoclonal antibodies. The signal-to-noise ratios (S/N) of extracted ion electropherograms of zwitterionic analytes were enhanced by approximately two orders of magnitude with a tradeoff of a shortened separation window. Online focusing improved the MS signal intensity of a diluted antibody digest, enabling more precursor ions to be analyzed with subsequent tandem mass spectrometric identification. It also broadened the concentration range of protein digest samples for which adequate sequence coverage data can be obtained. With only 0.9 ng of digested infliximab sample loaded into the capillary, 76 and 100% sequence coverage were realized for antibody heavy and light chains, respectively, after online focusing. Full coverage was achieved with 9 ng of injected digest. This article is protected by copyright. All rights reserved.

3.
Mol Cell Endocrinol ; : 110871, 2020 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-32450284

RESUMEN

FOXOs belong to the forkhead transcription factor superfamily, several of which are suggested to be involved in the control of food intake. Previously, we proved that the neuropeptide FF (NPFF) peptide was involved in feeding regulation in spotted sea bass. In the present study, seven members of the foxo family were identified in the whole genome of spotted sea bass. The distributions of these genes in different tissues were analyzed by qRT-PCR. Variations in the foxo1a and npff expression profiles during short-term starvation showed similar expression patterns. The colocalization of foxo1a and npff in the telencephalon, hypothalamus, stomach and intestine further provided evidence that foxo1a may act directly to promote the transcription of npff. Thirteen predicted FOXO1 binding sites were found in the 5' upstream region of npff. Luciferase assay results showed that FOXO1A was able to activate npff transcriptional responses by directly binding DNA response elements, and the key regulatory areas and sites of FOXO1A on the npff promoter were confirmed by deletion and site-directed mutagenesis analyses. These findings may help to elucidate the role of FOXO1 in the regulation of feeding processes in teleosts.

4.
J Proteome Res ; 2020 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-32338916

RESUMEN

Mass spectrometry is a powerful tool for de novo sequencing of novel proteins. Recent efforts in this area have mainly focused on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Here, we present an alternative method, capillary electrophoresis tandem mass spectrometry (CE-MS/MS), for sequencing novel monoclonal antibodies. Using less than 200 ng in total of tryptic digest sample in a triplicated measurement, CE-MS/MS with pH-mediated focusing successfully sequenced mAb infliximab with 100% sequence coverage and 100% accuracy for the light chain and 96% coverage and 93% accuracy for the heavy chain. It was also demonstrated that CE-MS/MS gives comparable results, and in some cases, even better results, as compared to LC-MS/MS when used as a standalone technique. A combined workflow using both CE-MS/MS and LC-MS/MS was also used to sequence a novel antibody, anti-CD-176, resulting in the first proposed sequence for this mAb.

5.
Nat Ecol Evol ; 2020 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-32284581

RESUMEN

The genetic basis for divergence in developmental gene expression among species is poorly understood, despite growing evidence that such changes underlie many interesting traits. Here we quantify transcription in hybrids of Heliocidaris tuberculata and Heliocidaris erythrogramma, two closely related sea urchins with highly divergent developmental gene expression and life histories. We find that most expression differences between species result from genetic influences that affect one stage of development, indicating limited pleiotropic consequences for most mutations that contribute to divergence in gene expression. Activation of zygotic transcription is broadly delayed in H. erythrogramma, the species with the derived life history, despite its overall faster premetamorphic development. Altered expression of several terminal differentiation genes associated with the derived larval morphology of H. erythrogramma is based largely on differences in the expression or function of their upstream regulators, providing insights into the genetic basis for the evolution of key life history traits.

6.
Sci Total Environ ; 713: 136443, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-31954251

RESUMEN

The aerosol extinction coefficient was an important factor for air quality. To estimate the aerosol extinction levels, widely used pure statistical models are generally not based on aerosol vertical structures. In this study, we estimated large-scale aerosol extinction coefficients by developing a new layer-resolved model with explicit inference for aerosol vertical distribution. The CALIOP aerosol profile, MODIS AOD and reanalysis boundary layer height data are used. The layer-resolved model was formulated by developing an explicit, steady and straightforward relationship between aerosol within boundary layer and corresponding AOD values. The estimated surface extinction coefficient from this model was compared against the values derived from station visibility observations in China in 2016. The results revealed that our model had outperformed the traditional one-layer model and the simplified two-layer model. Specifically, the numbers of ground stations with an NME value < 0.4 are enhanced by a percentage > 100%, with the NME values significantly decreased from 46%, 48% to 36% and RMSE values from 0.27, 0.25 to 0.21 km-1. Our model is easy for operational implementation thanks to its clear structure and input, and also informative to understand aerosol vertical distributions. Furthermore, this work will also be beneficial to air quality modeling studies to improve accuracy estimating ground-level PM2.5 concentrations.

7.
Haematologica ; 2020 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-31974191

RESUMEN

Hemophilia B is an X-linked recessive bleeding disorder caused by abnormalities in the coagulation factor IX gene. Without prophylactic treatment, patients experience frequent spontaneous bleeding episodes. Well-characterized animal models are valuable for determining the pathobiology of the disease and testing novel therapeutic innovations. Here, we generated a porcine model of hemophilia B using a combination of CRISPR/Cas9 and somatic cell nuclear transfer. Moreover, we tested the possibility of hemophilia B therapy by gene insertion. Frequent spontaneous joint bleeding episodes that occurred in hemophilia B pigs allowed a thorough investigation of the pathological process of hemophilic arthropathy. In contrast to the hemophilia B pigs, which showed a severe bleeding tendency and joint damage, the transgenic pigs carrying human coagulation factor IX exhibited a partial improvement of bleeding. In summary, this study not only offers a translational hemophilia B model for exploring the pathological process of hemophilic arthropathy but also provides a possibility for the permanent correction of hemophilia in the future by genome editing in situ.

8.
Int Immunol ; 32(2): 73-88, 2020 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-31555812

RESUMEN

Signal transducer and activator of transcription 3 (STAT3) is involved in many biological processes, including immunity and cancer. STAT3 becomes phosphorylated at Tyr705 and Ser727 on IL-6 stimulation. Phospho-Tyr705 (pY705) stabilizes the STAT3 dimer with reciprocal interactions between pY705 and the SH2 of the other molecule and phospho-Ser727 (pS727) accelerates pY705 dephosphorylation. We study how pS727 regulates STAT3 in both structural and biological perspectives. Using STAT3 reconstituted in HepG2-stat3-knockout cells, we show that pS727, together with a handshake N-terminal domain (NTD) interaction, causes rapid inactivation of STAT3 for pY705 dephosphorylation and a chromosome region maintenance 1 (CRM1)-independent nuclear export, which is critical for faithful STAT3 response to the cellular signals. The various N-terminal tags, GFP-related Ruby and FLAG, rendered the export CRM1-dependent and especially FLAG-tag caused nuclear accumulation of STAT3, indicating the presence of conformational changes in inactivation. Impaired reactivation of STAT3 by S727A or FLAG-tag delayed or inhibited the IL-6-induced saa1 mRNA expression, respectively. The detailed analysis of the pY705-SH2 structure identified the C-terminal tail (CTT) from L706 to P715 as a key regulator of the CTT-CTT intermolecular and the CTT-SH2 intramolecular interactions that support pY705-SH2 association. The functional studies using multiple STAT3 mutants indicated that the degree of the two interactions determines the stability of pY705-SH2 interaction. Importantly, Pro715 was critical for the pS727's destabilizing activity and the known phosphorylation and acetylation at the CTT structurally inhibited the pY705-SH2 interaction. Thus, pS727 triggers pY705-SH2 dissociation by weakening the supportive interactions likely through CTT modulation, inducing rapid cycles of STAT3 activation-inactivation for proper function of STAT3.

9.
Cell Mol Life Sci ; 77(4): 719-733, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31302752

RESUMEN

Cytidine base editors (CBEs) have been demonstrated to be useful for precisely inducing C:G-to-T:A base mutations in various organisms. In this study, we showed that the BE4-Gam system induced the targeted C-to-T base conversion in porcine blastocysts at an efficiency of 66.7-71.4% via the injection of a single sgRNA targeting a xeno-antigen-related gene and BE4-Gam mRNA. Furthermore, the efficiency of simultaneous three gene base conversion via the injection of three targeting sgRNAs and BE4-Gam mRNA into porcine parthenogenetic embryos was 18.1%. We also obtained beta-1,4-N-acetyl-galactosaminyl transferase 2, alpha-1,3-galactosyltransferase, and cytidine monophosphate-N-acetylneuraminic acid hydroxylase deficient pig by somatic cell nuclear transfer, which exhibited significantly decreased activity. In addition, a new CBE version (termed AncBE4max) was used to edit genes in blastocysts and porcine fibroblasts (PFFs) for the first time. While this new version demonstrated a three genes base-editing rate of 71.4% at the porcine GGTA1, B4galNT2, and CMAH loci, it increased the frequency of bystander edits, which ranged from 17.8 to 71.4%. In this study, we efficiently and precisely mutated bases in porcine blastocysts and PFFs using CBEs and successfully generated C-to-T and C-to-G mutations in pigs. These results suggest that CBEs provide a more simple and efficient method for improving economic traits, reducing the breeding cycle, and increasing disease tolerance in pigs, thus aiding in the development of human disease models.

10.
J Diabetes Investig ; 11(1): 192-198, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31145539

RESUMEN

AIMS/INTRODUCTION: Dyslipidemia is commonly present in type 2 diabetes mellitus patients. Recently, the triglyceride : high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel parameter of lipid abnormality, has been seen as an independent predictor for incident diabetes. However, the correlation of the TG/HDL-C ratio with incident diabetes in the Chinese population and how this relationship is impacted by sex have been rarely studied. In the present study, the correlation of the TG/HDL-C ratio with incident diabetes is investigated between different sexes of the Chinese population. MATERIALS AND METHODS: A total of 116,855 participants who were free of diabetes at baseline were enrolled in the study. The participants were grouped by the median value (0.82) of the TG/HDL-C ratio. Then, participants were further analyzed according to their sex. Cumulative incidence and person-years incidence were used to express the incidence rate. The predictive value of the TG/HDL-C ratio for incident diabetes was probed by the Cox regression proportional hazards model. RESULTS: The mean age of the participants was 44.1 ± 12.9 years, and 53% of participants (n = 62,868) were the men. A total of 2,685 incident diabetes cases occurred during the 3.1 years of the median follow-up period. The cumulative incidence in total incident diabetes patients, men and women was 2.30% (2.21-2.38%), 3.01% (2.87-3.14%) and 1.47% (1.37-1.57%), respectively. After the adjustment of multivariate factors, the multivariate Cox regression analysis results showed that a higher TG/HDL-C ratio was the independent predictive factor of incident diabetes in men (hazard ratio 1.30, 95% confidence interval 1.03-1.64), compared with women (hazard ratio 0.85, 95% confidence interval 0.53-1.38). CONCLUSIONS: Among the Chinese population, the TG/HDL-C ratio is an independent predictor for incident diabetes in male patients.

11.
Anat Rec (Hoboken) ; 303(3): 527-543, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31883312

RESUMEN

Analysis of gene expression has the potential to assist in the understanding of multiple cellular processes including proliferation, cell-fate specification, senesence, and activity in both healthy and disease states. Zebrafish model has been increasingly used to understand the process of hearing and the development of the vertebrate auditory system. Within the zebrafish inner ear, there are three otolith organs, each containing a sensory macula of hair cells. The saccular macula is primarily involved in hearing, the utricular macula is primarily involved in balance and the function of the lagenar macula is not completely understood. The goal of this study is to understand the transcriptional differences in the sensory macula associated with different otolith organs with the intention of understanding the genetic mechanisms responsible for the distinct role each organ plays in sensory perception. The sensory maculae of the saccule, utricle, and lagena were dissected out of adult Et(krt4:GFP)sqet4 zebrafish expressing green fluorescent protein in hair cells for transcriptional analysis. The total RNAs of the maculae were isolated and analyzed by RNA GeneChip microarray. Several of the differentially expressed genes are known to be involved in deafness, otolith development and balance. Gene expression among these otolith organs was very well conserved with less than 10% of genes showing differential expression. Data from this study will help to elucidate which genes are involved in hearing and balance. Furthermore, the findings of this study will assist in the development of the zebrafish model for human hearing and balance disorders. Anat Rec, 303:527-543, 2020. © 2019 American Association for Anatomy.

12.
Sensors (Basel) ; 19(19)2019 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-31569430

RESUMEN

Accurate crop classification is the basis of agricultural research, and remote sensing is the only effective measuring technique to classify crops over large areas. Optical remote sensing is effective in regions with good illumination; however, it usually fails to meet requirements for highly accurate crop classification in cloud-covered areas and rainy regions. Synthetic aperture radar (SAR) can achieve active data acquisition by transmitting signals; thus, it has strong resistance to cloud and rain interference. In this study, we designed an improved crop planting structure mapping framework for cloudy and rainy regions by combining optical data and SAR data, and we revealed the synchronous-response relationship of these two data types. First, we extracted geo-parcels from optical images with high spatial resolution. Second, we built a recurrent neural network (RNN)-based classifier suitable for remote sensing images on the geo-parcel scale. Third, we classified crops based on the two datasets and established the network. Fourth, we analyzed the synchronous response relationships of crops based on the results of the two classification schemes. This work is the basis for the application of remote sensing data for the fine mapping and growth monitoring of crop planting structures in cloudy and rainy areas in the future.

13.
Plant Biotechnol J ; 2019 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-31584235

RESUMEN

The ability to interpret daily and seasonal fluctuations, latitudinal and vegetation canopy variations in light and temperature signals is essential for plant survival. However, the precise molecular mechanisms transducing the signals from light and temperature perception to maintain plant growth and adaptation remain elusive. We show that far-red light induces PHYTOCHROME-INTERACTING TRANSCRIPTION 4 (SlPIF4) accumulation under low-temperature conditions via phytochrome A in Solanum lycopersicum (tomato). Reverse genetic approaches revealed that knocking out SlPIF4 increases cold susceptibility, while overexpressing SlPIF4 enhances cold tolerance in tomato plants. SlPIF4 not only directly binds to the promoters of the C-REPEAT BINDING FACTOR (SlCBF) genes and activates their expression but also regulates plant hormone biosynthesis and signals, including abscisic acid, jasmonate and gibberellin (GA), in response to low temperature. Moreover, SlPIF4 directly activates the SlDELLA gene (GA-INSENSITIVE 4, SlGAI4) under cold stress, and SlGAI4 positively regulates cold tolerance. Additionally, SlGAI4 represses accumulation of the SlPIF4 protein, thus forming multiple coherent feed-forward loops. Our results reveal that plants integrate light and temperature signals to better adapt to cold stress through shared hormone pathways and transcriptional regulators, which may provide a comprehensive understanding of plant growth and survival in a changing environment.

14.
FASEB J ; 33(12): 13920-13934, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31648566

RESUMEN

VEGF is a critical driver of ocular neovascularization under disease conditions. Current therapeutic strategies rely on intraocular delivery of VEGF-antagonizing reagents, which results in sustained suppression of pathogenic vascularization. Although significant advancement has been achieved in VEGF antagonism, substantial adverse effects have been reported in retrospective clinical studies. To study mechanisms for VEGF antagonism-associated adverse effects in visual system, we intravitreally delivered recombinant adeno-associated virus-mediated expression of soluble Fms-related tyrosine kinase-1 (rAAV.sFLT-1), the extracellular domain of VEGF receptor, and analyzed the morphology and functions of retinal tissue. Here, we confirmed that intraocular VEGF antagonism induced retinal degeneration and gliosis. The functional deficit in retinal response to visual stimulation was also demonstrated in rAAV.sFLT-1-treated eyes by electroretinogram. Moreover, high-throughput RNA sequencing analysis suggests that VEGF antagonism activates retinal degeneration, inflammation, and other adverse effects. Taken together, our findings have shed light on pathogenic mechanisms for VEGF antagonism-associated adverse effects and potential therapeutic targets.-Xiao, M., Liu, Y., Wang, L., Liang, J., Wang, T., Zhai, Y., Wang, Y., Liu, S., Liu, W., Luo, X., Wang, F., Sun, X. Intraocular VEGF deprivation induces degeneration and fibrogenic response in retina.

15.
Artículo en Inglés | MEDLINE | ID: mdl-31474940

RESUMEN

Neurokinin B (NKB) is a member of the tachykinin (tac) family that plays important roles in mammalian growth by modulating prolactin (PRL) synthesis and secretion and causing contraction of the stomach and intestine. However, its potential role in regulating growth of teleosts is less clear. We aimed to explore the role that NKB plays in regulating fish growth using the spotted sea bass (Lateolabrax maculatus) as a model. In the present study, two tac3 and two tacr3 genes were identified in the spotted sea bass. Sequence analysis showed that two tac3 transcripts, tac3a and tac3b, encode four NKBs: NKBa-13, NKBa-10, NKBb-13, and NKBb-10. Expression analysis in different tissues showed that both genes are highly expressed in the brain, stomach and intestine of the spotted sea bass. In situ hybridization indicated that the tac3a and tac3b mRNAs are both localized in several brain regions, such as the telencephalon and hypothalamus, and that tacr3a and tacr3b are localized in the intestinal villus and gastric gland. To investigate the potential role of NKBs in regulating growth, in vitro experiments were performed to detect the effect of NKBs on growth-related gene expression in the brain and brain-gut peptide (BGP)-related genes in the stomach and intestine. NKBb-13 was the most critical ligand in regulating the expression of growth-related genes in the brain and brain-gut peptide (BGP)-related genes in the stomach. The expression of cholecystokinin (cck) was enhanced by NKBa-13, NKBa-10, and NKBb-10 but not NKBb-13 in the intestine. In general, our results showed that NKBs participate in regulating the growth of spotted sea bass.

16.
Electrophoresis ; 40(21): 2899-2907, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31407816

RESUMEN

Capillary isoelectric focusing (cIEF) was online coupled to a Q-TOF MS by a flow-through microvial interface for the analysis of therapeutic mAb. Intact molecular weights obtained from the mass spectrum deconvolution of separated charge variants provided information on the structural heterogeneity of therapeutic mAbs. A sandwich cIEF-MS configuration composed of anolyte, sample, and catholyte segments sequentially injected into a neutrally coated capillary was used for the charge heterogeneity separation of four mAbs. Acetic acid and ammonium hydroxide were used in places of the non-volatile acids and bases commonly used for IEF but are incompatible with online MS detection. Glycerol was added as the anti-convective reagent. A chemical modifier was mixed with the cIEF effluent in the flow-throw microvial to maintain the ESI stability and to mitigate ion suppression from the co-eluted carrier ampholytes and glycerol. Analysis of mAb samples have shown relative populations of two basic variants originating from C-terminal lysine process and acidic variant of deamidation. The lysine clippings, deamidation, and sialic acid modification in oligosaccharide chains were revealed in infliximab. Two lysine clipping variants and a deamidated variant were observed in adalimumab. The duplicate analyses of a reference mAb demonstrated five charge variants separated by cIEF due to some unidentified modifications, as their mass spectra shared close similarities. The mAb analyses demonstrated the feasibility of the cIEF-MS method, and they demonstrated how charge and structural variants and minor differences in therapeutic mAbs are observed with this technology. Online cIEF-MS is an information rich technology with high throughput, demonstrated by the initial data presented here.

17.
Fish Shellfish Immunol ; 92: 782-791, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31288100

RESUMEN

Toll-like receptor (TLR) genes are the earliest reported pathogen recognition receptors (PRRs) and have been extensively studied. These genes play pivotal roles in the innate immune defense against pathogen invasion. In this study, a total of 16 tlr genes were identified and characterized in spotted sea bass (Lateolabrax maculatus). The tlr genes of spotted sea bass were classified into five subfamilies (tlr1-subfamily, tlr3-subfamily, tlr5-subfamily, tlr7-subfamily, and tlr11-subfamily) according to the phylogenetic analysis, and their annotations were confirmed by a syntenic analysis. The protein domain analysis indicated that most tlr genes had the following three major TLR protein domains: a leucine-rich repeat (LRR) domain, a transmembrane region (TM) and a Toll/interleukin-1 receptor (TIR) domain. The tlr genes in spotted sea bass were distributed in 11 of 24 chromosomes. The mRNA expression levels of 16 tlr genes in response to Vibrio harveyi infection were quantified in the head kidney. Most genes were downregulated following V. harveyi infection, while only 5 tlr genes, including tlr1-1, tlr1-2, tlr2-2, tlr5, and tlr7, were significantly upregulated. Collectively, these results help elucidate the crucial roles of tlr genes in the immune response of spotted sea bass and may supply valuable genomic resources for future studies investigating fish disease management.


Asunto(s)
Lubina/genética , Lubina/inmunología , Enfermedades de los Peces/inmunología , Genoma/inmunología , Inmunidad Innata/genética , Receptores Toll-Like/genética , Receptores Toll-Like/inmunología , Animales , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Perfilación de la Expresión Génica , Vibrio/fisiología , Vibriosis/inmunología , Vibriosis/veterinaria
18.
Dev Biol ; 452(1): 34-42, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31075220

RESUMEN

Specification of the primordial germ cells (PGCs) is essential for sexually reproducing animals. Although the mechanisms of PGC specification are diverse between organisms, the RNA binding protein Nanos is consistently required in the germ line in all species tested. How Nanos is selectively expressed in the germ line, however, remains largely elusive. We report that in sea urchin embryos, the early expression of Nanos2 in the PGCs requires the maternal Wnt pathway. During gastrulation, however, Nanos2 expression expands into adjacent somatic mesodermal cells and this secondary Nanos expression instead requires Delta/Notch signaling through the forkhead family member FoxY. Each of these transcriptional regulators were tested by chromatin immunoprecipitation analysis and found to directly interact with a DNA locus upstream of Nanos2. Given the conserved importance of Nanos in germ line specification, and the derived character of the micromeres and small micromeres in the sea urchin, we propose that the ancestral mechanism of Nanos2 expression in echinoderms was by induction in mesodermal cells during gastrulation.


Asunto(s)
Gastrulación/fisiología , Regulación del Desarrollo de la Expresión Génica/fisiología , Proteínas de Unión al ARN/metabolismo , Strongylocentrotus purpuratus/embriología , Transcripción Genética/fisiología , Vía de Señalización Wnt/fisiología , Animales , Células Germinativas/citología , Células Germinativas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de la Membrana/metabolismo , Mesodermo/citología , Mesodermo/embriología , Receptores Notch/metabolismo , Strongylocentrotus purpuratus/citología
19.
Life Sci ; 227: 201-211, 2019 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-31002917

RESUMEN

AIMS: Colorectal cancer syndrome has been one of the greatest concerns in the world. Although several epidemiological studies have shown that hepatic low lipoprotein lipase (LPL) mRNA expression may be associated with dyslipidemia and tumor progression, it is still not known whether the liver plays an essential role in hyperlipidemia of ApcMin/+ mice. MAIN METHODS: We measured the expression of metabolic enzymes that involved fatty acid uptake, de novo lipogenesis (DNL), ß-oxidation and investigated hepatic triglyceride production in the liver of wild-type and ApcMin/+ mice. KEY FINDINGS: We found that hepatic fatty acid uptake and DNL decreased, but there was no significant difference in fatty acid ß-oxidation. Interestingly, the production of hepatic very low-density lipoprotein-triglyceride (VLDL-TG) decreased at 20 weeks of age, but marked steatosis was observed in the livers of the ApcMin/+ mouse. To further explore hypertriglyceridemia, we assessed the function of hepatic glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) for the first time. GPIHBP1 is governed by the transcription factor octamer-binding transcription factor-1 (Oct-1) which are involved in the nuclear factor-κB (NF-κB) signaling pathway in the liver of ApcMin/+ mice. Importantly, it was also confirmed that sn50 (100 µg/mL, an inhibitor of the NF-κB) reversed the tumor necrosis factor α (TNFα)-induced Oct-1 and GPIHBP1 reduction in HepG2 cells. SIGNIFICANCE: Altogether, these findings highlighted a novel role of GPIHBP1 that might be responsible for hypertriglyceridemia in ApcMin/+ mice. Hypertriglyceridemia in these mice may be associated with their hepatic lipid metabolism development.


Asunto(s)
Hígado/metabolismo , Receptores de Lipoproteína/fisiología , Triglicéridos/metabolismo , Animales , Caquexia/metabolismo , Caquexia/fisiopatología , Neoplasias del Colon/fisiopatología , Ácidos Grasos/metabolismo , Hígado Graso/patología , Regulación de la Expresión Génica/genética , Células Hep G2 , Humanos , Hiperlipidemias/genética , Metabolismo de los Lípidos/genética , Lípidos/fisiología , Lipogénesis/fisiología , Lipólisis/fisiología , Lipoproteínas VLDL/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Factor 1 de Transcripción de Unión a Octámeros/fisiología , Receptores de Lipoproteína/genética , Receptores de Lipoproteína/metabolismo , Triglicéridos/genética , Factor de Necrosis Tumoral alfa/fisiología
20.
Phys Chem Chem Phys ; 21(15): 8081-8091, 2019 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-30932098

RESUMEN

The gas-phase ozonolysis mechanism of 3-carene is investigated using high level quantum chemistry and kinetic calculations. The reaction follows the Criegee mechanism with an initial addition of O3 to the [double bond splayed left]C[double bond, length as m-dash]C[double bond splayed right] bond, followed by a chain of unimolecular isomerizations, as 3-carene + O3→ POZs (primary ozonides) → CIs (Criegee intermediates, 4 conformers) → Ps (products). In the course of the reaction, a large excess of energy retained in the POZs* lead to the prompt unimolecular processes in POZs*, CIs*, and Ps*, and only ∼4% of CIs* could be stabilized by collision at 298 K and 760 Torr. From RRKM-ME calculations, the VHPs* could further dissociate to vinoxy-type radical and OH radical, the SOZs* could isomerize to 3-caronic acid, and DIOs* could be stabilized via collision. The fractional yield of OH radical, in the range of 0.56 to 0.59, agrees reasonably well with the previously measured value of 1.06 (with an uncertainty factor of 1.5).

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