Endometriosis is a common, chronic gynaecological disease affecting up to 10% of women in their reproductive years. Its aetiology still remains unclear, but evidence indicates genetic factors play a ...role. We previously identified a region of significant linkage on chromosome 7 in 52 families comprising at least three affected women, stretching ∼6.4 Mb. We screened coding regions and parts of the regulatory regions of three candidate genes with a known role in endometrial development and function-INHBA, SFRP4 and HOXA10-located under or very near the linkage peak, for potential causal mutations using Sanger sequencing. Sequencing was conducted in 47 cases from the 15 families contributing most to the linkage signal (Z
mean ≥ 1). Minor allele frequencies (MAFs) of observed variants were compared with MAFs from two publicly available reference populations of European ancestry: 60 individuals in HapMap and 150 individuals in the 1000 Genomes Project. A total of 11 variants were found, 5 (45%) of which were common (MAF > 0.05) among the 15 case families and the reference populations (P-values for MAF difference: 0.88-1.00). The remaining six were rare and unlikely to be individually or cumulatively responsible for the linkage signal. The results indicate that the coding regions of these three genes do not harbour mutations responsible for linkage to endometriosis in these families.
This paper presents the measured active and passive fluxes of carbon (C), nitrogen (N), and phosphorus (P) and their response to seasonal and event-driven oceanographic changes in the northern South ...China Sea (NSCS). The total vertical flux of carbon (TFC) is defined as the sum of active and passive fluxes of biogenic carbon in the surface layer, which may be considered as the central part of marine carbon cycle. These active and passive fluxes of N and P were also considered to understand stoichiometric flux patterns and the roles of nutrients involved in the TFC. The magnitudes of total C, N, and P fluxes were, respectively, estimated to be 71.9–347 (mean ± SD, 163 ± 70) mgCm-2d-1, 13.0–30.5 (21.2.± 4.9) mgNm-2d-1, and 1.02–2.97 (1.94 ± 0.44) mgPm-2d-1, which were higher than most previously reported vertical fluxes in open oceans, likely because a quarter of the fluxes was contributed from active fluxes that were unaccounted for in vertical fluxes previously. Moreover, the passive fluxes dominated the total vertical fluxes and were estimated to be 65.3–255 (125 ± 64.9) mgCm-2d-1 (77 ± 52 % of total C flux), 11.9–23.2 (17.6 ± 4.2) mgNm-2d-1 (83 ± 28 % of total N flux), and 0.89–1.98 (1.44 ± 0.33) mgPm-2d-1 (74 ± 24 % of total P flux). Vertical fluxes of dissolved organic C, N, and P were small (< 5 %) relative to passive fluxes. The contrasting patterns of active and passive fluxes found between summer and winter could mainly be attributed to surface warming and stratification in summer and cooling and wind-induced turbulence for pumping nutrients into the euphotic zone in winter. In addition to seasonal variations, the impact of anticyclonic eddies and internal-wave events on enhancing active and passive fluxes was apparent in the NSCS. Both active and passive fluxes were likely driven by nutrient availability within the euphotic zone, which was ultimately controlled by the changes in internal and external forcings. The nutrient availability also determined the inventory of chlorophyll a and new production, thereby allowing the estimates of active and passive fluxes for unmeasured events. To a first approximation, the South China Sea (SCS) may effectively transfer 0.208 ± 0.089 Gt C yr−1 into the ocean's interior, accounting for approximately 1.89 ± 0.81 % of the global C flux. The internal forcing and climatic conditions are likely critical factors in determining the seasonal and event-driven variability of total vertical fluxes in the NSCS.
Abstract The safety of future fusion reactors is critically dependent on the tritium (T) retention in plasma-facing materials. Hydrogen isotope (HI) exchange offers a method to redistribute HIs ...within solid materials, presenting a feasible approach for removing T from bulk materials and trapped by strong trapping sites. Nonetheless, unraveling the intricate mechanism behind HI exchange remains an urgent yet formidable challenge. This study undertakes a comprehensive investigation into the mechanism of HI exchange in tungsten materials across multiple scales. First, we developed a multi-component hydrogen isotope transport and exchange model (HIDTX) based on classical rate theory. The model validation was further carried out, demonstrating good consistency with the well-controlled laboratory experiments. From the results of different comparative models in HIDTX, it is found that the reduction in deuterium retention due to HI exchange was primarily driven by three synergistic effects: competitive re-trapping, collision, and swapping effects. Through molecular dynamics (MD) and first-principles calculations, the microscopic mechanism of HI exchange was revealed to be that the presence of hydrogen atoms in the interstitial sites surrounding a vacancy in tungsten decreased the binding energy between the vacancy and hydrogen. Meanwhile, we discovered that the combination of thermal desorption and HI exchange can significantly lower the temperature required for the hydrogen removal and enhance the removal rate. Particularly, the hydrogen removal time can be shortened by approximately 95% with simultaneous HI exchange compared to that with only thermal desorption. This work provides a practical guideline for comprehending and subsequently designing for efficient T removal in future nuclear fusion materials.
The feasibility of noninvasive imaging of adenoviral-mediated herpes virus type one thymidine kinase (HSV1-tk) gene transfer and expression was assessed in a well-studied animal model of metastatic ...colon carcinoma of the liver. Tumors were produced in syngeneic BALB/c mice by intrahepatic injection of colon carcinoma cells (MCA-26). Seven days later, three different doses (3 x 10(8), 1 x 10(8), and 3 x 10(7) plaque-forming units (pfu) of the recombinant adenoviral vector ADV. Rous sarcoma virus (RSV)-tk bearing the HSV1-tk gene were administered by intratumoral injection in separate groups of mice. Two control groups of tumor-bearing mice received intratumoral injections of the control adenoviral vector dl-312 or buffer alone, respectively. T2-weighted magnetic resonance (MR) images of mice were obtained before administering the virus and provided an anatomical reference of hepatic tumor localization. Eighteen h after the virus injection, one group of animals was given i.v. injections of 300 microCi of no-carrier-added 5-131I-2'-fluoro-1-beta-D-arabinofuranosyluracil (FIAU) and imaged 24 h later with a gamma camera. In some animals, the tumors were sampled and processed for histology and quantitative autoradiography (QAR). The gamma camera images demonstrated highly specific localization of 131IFIAU-derived radioactivity to the area of ADV.RSV-tk-injected tumors in the liver, which was confirmed by coregistering the gamma camera and T2-weighted MR images. There was no accumulation of 131IFIAU-derived radioactivity in tumors that were injected with the control vector or injection solution alone. A more precise distribution of radioactivity in the area of transfected tumor was obtained by histological and QAR comparisons. A heterogeneous pattern of radioactivity distribution in transfected tumors was observed. A punctate pattern of radioactivity distribution was observed in peritumoral liver tissue in animals given injections of 3 x 10(8) and 1 x 10(8) pfu of ADV.RSV-tk but not in animals given injections of 3 x 10(7) pfu nor in control animals. A QAR-microscopic comparison showed that the punctate areas of radioactivity colocalized with cholangial ducts. The level of 131IFIAU-derived radioactivity accumulation (HSV1-tk expression) in the transfected tumors was viral dose-dependent. The viral dose-dependency of radioactivity accumulation was more pronounced in peritumoral liver, which was confirmed by reverse transcription-PCR analysis. A separate group of tumor-bearing animals received different doses of ADV.RSV-tk vector followed by treatment with ganciclovir (GCV), 10 mg/kg i.p. b.i.d. for 6 days. The ADV.RSV-tk transfected tumors significantly regressed with GCV treatment; the control tumors continued to grow. During the GCV treatment, the levels of liver transaminases (ALT and AST) were significantly increased in animals that received injections of 3 x 10(8) and 1 x 10(8) pfu of ADV.RSV-tk but not in animals that received injections of 3 x 10(7) pfu and in control animals. The observed liver toxicity confirms the results of gamma camera and QAR imaging, which demonstrated an unwanted spread of ADV.RSV-tk vector and HSV1-tk expression in peritumoral and remote liver tissue at higher doses. These and our previous results indicate that noninvasive imaging of adenoviral-mediated HSV1-tk gene expression is feasible for monitoring cancer gene therapy in patients.
<div class="content" data-loaded="yes">We report that electroproduction form factors describing the γ*p → Δ + ( 1232 ) , Δ + ( 1600 ) transitions are computed using a fully dynamical diquark-quark ...approximation to the Poincaré-covariant three-body bound-state problem in relativistic quantum field theory. In this approach, the Δ ( 1600 ) is an analogue of the Roper resonance in the nucleon sector, appearing as the simplest radial excitation of the Δ ( 1232 ) . Precise measurements of the γ*p → Δ + ( 1232 ) transition already exist on 0≤Q2≲8 GeV2 , and the calculated results compare favorably with the data outside the meson-cloud domain. The predictions for the γ*p → Δ + ( 1600 ) magnetic dipole and electric quadrupole transition form factors are consistent with the empirical values at the real photon point, and extend to Q2≈6mp2 , enabling a meaningful direct comparison with experiment once analysis of existing data is completed. In both cases, the electric quadrupole form factor is particularly sensitive to deformation of the Δ -baryons. Interestingly, while the γ*p → Δ + ( 1232 ) transition form factors are larger in magnitude than those for γ*p → Δ + ( 1600 ) in some neighborhood of the real photon point, this ordering is reversed on Q2≳2mp2 , suggesting that the γ*p → Δ + ( 1600 ) transition is more localized in configuration space.
•Dietary sulfur amino acids affected serum biochemical variables of weaned piglets.•Dietary sulfur amino acids did not affect jejunal mucosal amino acid profiles.•Dietary sulfur amino acids lowered ...jejunal composition of alanine.•Dietary sulfur amino acids reduced jejunal mucosal sulfur amino acids metabolism.•Dietary sulfur amino acids reduced inflammation in jejunal mucosa of weaned piglets.
Sulfur amino acids (SAAs) play critical roles in biological functions and protection against diseases. The present study was conducted to investigate the impact of dietary SAAs on serum biochemical variables, jejunal mucosal amino acid contents, and intestinal inflammation in weaned piglets. Forty Duroc × Landrace × Yorkshire piglets at 21 days of age were weaned and randomly assigned to one of five diets that contained 0.53, 0.63, 0.74, 0.85, or 0.96% SAAs, which corresponded to 70, 85, 100, 115, or 130% of the SAAs: Lysine (Lys) ratio recommended by National Research Council (NRC, 2012). Dietary supplementation with SAAs significantly enhanced (P < 0.05) serum creatinine and low density lipoprotein. Serum glucose was reduced (P < 0.01) and there was a tendency of decrease for total cholesterol (TC; P = 0.052) and triglycerides (TG; P = 0.069) in response to dietary SAAs supplementation. No significant difference was observed in jejunal mucosal amino acid profiles, but dietary supplementation with SAAs lowered (P < 0.05) jejunal composition of Ala and tended to decrease the composition of His (P = 0.090). Dietary supplementation with 0.63% or more SAAs reduced (P < 0.05) the mRNA expression of genes involved in SAAs metabolism (NSF1 and CBS), as well as genes related to inflammation (TNF-a, TGF-β, and IL-1β). These results indicate that dietary SAAs may involve in regulating lipid metabolism and intestinal inflammation of weaning piglets.
Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a ...functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.
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