767 research outputs found

    Transcriptomic analyses of regenerating adult feathers in chicken

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    Transcriptome Expression Data. Table of mapped reads to Galgal4 transcripts for all 15 data sets. FPKM (Fragments per kilobase of exon per million fragments mapped): normalized transcript abundance values for each gene in the indicated tissues. (CSV 1314 kb

    Different relationship between ANGPTL3 and HDL components in female non-diabetic subjects and type-2 diabetic patients

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    BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is a major lipoprotein regulator and shows positive correlation with high-density lipoprotein-cholesterol (HDL-c) in population studies and ANGPTL3 mutated subjects. However, no study has looked its correlation with HDL components nor with HDL function in patients with type 2 diabetes mellitus (T2DM). METHODS: We studied 298 non-diabetic subjects and 300 T2DM patients who were randomly recruited in the tertiary referral centre. Plasma levels of ANGPTL3 were quantified by ELISA. Plasma samples were fractionated to obtain HDLs. HDL components including apolipoprotein A-I (apoA-I), triglyceride, serum amyloid A (SAA), phospholipid and Sphingosine-1-phosphate were measured. HDLs were isolated from female controls and T2DM patients by ultracentrifugation to assess cholesterol efflux against HDLs. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, body mass index and lipid lowering drugs were performed in male or female non-diabetic participants or diabetic patients, respectively. RESULTS: We demonstrated that plasma level of ANGPTL3 was lower in female T2DM patients than female controls although no difference of ANGPTL3 levels was detected between male controls and T2DM patients. After adjusting for confounding factors, one SD increase of ANGPTL3 (164.6 ng/ml) associated with increase of 2.57 mg/dL cholesterol and 1.14 μg/mL apoA-I but decrease of 47.07 μg/L of SAA in HDL particles of non-diabetic females (p < 0.05 for cholesterol and SAA; p < 0.0001 for apoA-I). By contrast, 1-SD increase of ANGPTL3 (159.9 ng/ml) associated with increase of 1.69 mg/dl cholesterol and 1.25 μg/mL apoA-I but decrease of 11.70 μg/L of SAA in HDL particles of female diabetic patients (p < 0.05 for cholesterol; p < 0.0001 for apoA-I; p = 0.676 for SAA). Moreover, one SD increase of ANGPTL3 associated with increase of 2.11 % cholesterol efflux against HDLs in non-diabetic females (p = 0.071) but decrease of 1.46 % in female T2DM patients (p = 0.13) after adjusting for confounding factors. CONCLUSIONS: ANGPTL3 is specifically correlated with HDL-c, apoA-I, SAA and HDL function in female non-diabetic participants. The decrease of ANGPTL3 level in female T2DM patients might contribute to its weak association to HDL components and function. ANGPTL3 could be considered as a novel therapeutic target for HDL metabolism for treating diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-016-0450-1) contains supplementary material, which is available to authorized users

    IKK-induced NF-kappa B1 p105 proteolysis is critical for B cell antibody responses to T cell-dependent antigen

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    The importance of IκB kinase (IKK)–induced proteolysis of NF-κB1 p105 in B cells was investigated using Nfkb1SSAA/SSAA mice, in which this NF-κB signaling pathway is blocked. Nfkb1SSAA mutation had no effect on the development and homeostasis of follicular mature (FM) B cells. However, analysis of mixed bone marrow chimeras revealed that Nfkb1SSAA/SSAA FM B cells were completely unable to mediate T cell–dependent antibody responses. Nfkb1SSAA mutation decreased B cell antigen receptor (BCR) activation of NF-κB in FM B cells, which selectively blocked BCR stimulation of cell survival and antigen-induced differentiation into plasmablasts and germinal center B cells due to reduced expression of Bcl-2 family proteins and IRF4, respectively. In contrast, the antigen-presenting function of FM B cells and their BCR-induced migration to the follicle T cell zone border, as well as their growth and proliferation after BCR stimulation, were not affected. All of the inhibitory effects of Nfkb1SSAA mutation on B cell functions were rescued by normalizing NF-κB activation genetically. Our study identifies critical B cell-intrinsic functions for IKK-induced NF-κB1 p105 proteolysis in the antigen-induced survival and differentiation of FM B cells, which are essential for T-dependent antibody responses

    Exploring the first-time transition to parenthood in mainland China: a qualitative study on the experiences of fathers and mothers using the transition shock model

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    BackgroundThe transition to parenthood, which is influenced a lot by local parenting culture, is a dramatic stress for both men and women. Chinese social and cultural contexts form specific parental culture, shaping the unique experience of transition to parenthood. However, the understanding of the transition to parenthood in mainland China is limited. Additionally, few qualitative studies explored the transition to parenthood from both dyadic perspectives.AimTo explore the first-time transition to parenthood experience among mothers and fathers in mainland China during pregnancy, and compare the similarities and differences between their experiences in this transition period.MethodsA descriptive qualitative study was conducted with 36 parents, including 18 primiparous women and their husbands. Data were analyzed by directed content analysis guided by the Transition Shock Model. The interview texts were first analyzed at individual levels and subsequently at the couple level to identify dyadic themes.ResultsFive themes and thirteen sub-themes emerged from the data analysis, including role integration, health risk, dilemma of preparation, protective isolation, and multi-dimensional expectation. Unexpectedly, the experiences and perspectives of mothers and fathers regarding the transition to parenthood were found to be similar, with the exception of the sub-theme extra-care requirement.ConclusionThe findings shed light on the complex emotional journey and expectations of parents, as well as the challenges they face in terms of physical well-being, limited coping resources, and restricted social connections. Notably, fathers in China often shared the stress of the whole process during the transition period alongside mothers but often lacked accessible avenues for seeking and receiving support. These findings underscore the importance of actively involving fathers as a key support population in perinatal care, as well as the need for comprehensive support systems and tailored interventions to enhance the well-being and adaptation of parents

    Electromagnetic-Thermal Co-simulation Of Microstrip Filter

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    An electromagnetic-thermal co-simulation method is proposed for microstrip filter in this paper. The Maxwell equation is solved by discontinuous Galerkin time-domain (DGTD) method, while thermal simulation is carried out based on finite-element time-domain (FETD) method. Electromagnetic and thermal simulations are coupled by power loss and temperature-dependent conductivity. At last, the method is applied to analyze the microstrip low-pass filter

    Quinones as dienophiles in the Diels-Alder reaction: history and applications in total synthesis

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    In the canon of reactions available to the organic chemist engaged in total synthesis, the Diels–Alder reaction is among the most powerful and well understood. Its ability to rapidly generate molecular complexity through the simultaneous formation of two carboncarbon bonds is almost unrivalled, and this is reflected in the great number of reported applications of this reaction. Historically, the use of quinones as dienophiles is highly significant, being the very first example investigated by Diels and Alder. Herein, we review the application of the Diels–Alder reaction of quinones in the total synthesis of natural products. The highlighted examples span some 60 years from the landmark syntheses of morphine (1952) and reserpine (1956) by Gates and Woodward, respectively, through to the present day examples, such as the tetracyclines

    A high-Q metasurface signal isolator for 1.5T surface coil magnetic resonance imaging on the go

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    The combination of surface coils and metamaterials remarkably enhance magnetic resonance imaging (MRI) performance for significant local staging flexibility. However, due to the coupling in between, impeded signal-to-noise ratio (SNR) and low-contrast resolution, further hamper the future growth in clinical MRI. In this paper, we propose a high-Q metasurface decoupling isolator fueled by topological LC loops for 1.5T surface coil MRI system, increasing the magnetic field up to fivefold at 63.8 MHz. We have employed a polarization conversion mechanism to effectively eliminate the coupling between the MRI metamaterial and the radio frequency (RF) surface transmitter-receiver coils. Furthermore, a high-Q metasurface isolator was achieved by taking advantage of bound states in the continuum (BIC) for extremely high-field MRI and spectroscopy. An equivalent physical model of the miniaturized metasurface design was put forward through LC circuit analysis. This study opens up a promising route for the easy-to-use and portable surface coil MRI scanners

    A New Hip Fracture Risk Index Derived from FEA-Computed Proximal Femur Fracture Loads and Energies-to-Failure

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    Hip fracture risk assessment is an important but challenging task. Quantitative CT-based patient specific finite element analysis (FEA) computes the force (fracture load) to break the proximal femur in a particular loading condition. It provides different structural information about the proximal femur that can influence a subject overall fracture risk. To obtain a more robust measure of fracture risk, we used principal component analysis (PCA) to develop a global FEA computed fracture risk index that incorporates the FEA-computed yield and ultimate failure loads and energies to failure in four loading conditions (single-limb stance and impact from a fall onto the posterior, posterolateral, and lateral aspects of the greater trochanter) of 110 hip fracture subjects and 235 age and sex matched control subjects from the AGES-Reykjavik study. We found that the first PC (PC1) of the FE parameters was the only significant predictor of hip fracture. Using a logistic regression model, we determined if prediction performance for hip fracture using PC1 differed from that using FE parameters combined by stratified random resampling with respect to hip fracture status. The results showed that the average of the area under the receive operating characteristic curve (AUC) using PC1 was always higher than that using all FE parameters combined in the male subjects. The AUC of PC1 and AUC of the FE parameters combined were not significantly different than that in the female subjects or in all subjectsComment: 27 pages, 4 figure

    Lysosomal-associated protein transmembrane 5 ameliorates non-alcoholic steatohepatitis by promoting the degradation of CDC42 in mice.

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    Non-alcoholic steatohepatitis (NASH) has received great attention due to its high incidence. Here, we show that lysosomal-associated protein transmembrane 5 (LAPTM5) is associated with NASH progression through extensive bioinformatical analysis. The protein level of LAPTM5 bears a negative correlation with NAS score. Moreover, LAPTM5 degradation is mediated through its ubiquitination modification by the E3 ubquitin ligase NEDD4L. Discovered by experiments conducted on male mice, hepatocyte-specific depletion of Laptm5 exacerbates mouse NASH symptoms. In contrast, Laptm5 overexpression in hepatocytes exerts diametrically opposite effects. Mechanistically, LAPTM5 interacts with CDC42 and promotes its degradation through a lysosome-dependent manner under the stimulation of palmitic acid, thus inhibiting activation of the mitogen-activated protein kinase signaling pathway. Finally, adenovirus-mediated hepatic Laptm5 overexpression ameliorates aforementioned symptoms in NASH models

    Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

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    Human matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn(2+) atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes
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