In Fas/FasL-deficient mice anti-chromatin Ab production is T cell dependent and is not apparent until after 10 weeks of age. Early control of anti-chromatin antibodies may be due to the ...counterbalancing influence of Treg cells. Here we show that Treg cells block lpr/lpr gld/gld Th cells from providing help to anti-chromatin B cells in an in vivo transfer system. Interestingly, the percentage and absolute numbers of Foxp3 super(+) Treg cells is elevated in BALB/c-lpr/lpr gld/gld mice and increases with age compared to BALB/c mice. The majority of Foxp3 expression is found in the B220 super(-) CD4 super(+) T cell population, and Foxp3-expressing cells are localized in the splenic PALS (periarteriolar lymphocyte sheath). Strikingly, although the lack of functional Fas/FasL does not affect the ability of Treg cells to block Th cell proliferation, Treg cells can block the IFN- gamma differentiation of Th cells from BALB/c or young BALB-lpr/lpr gld/gld mice but not of pre-existing Th1 cells from older BALB/c-lpr/lpr gld/gld mice. Thus, we suggest autoantibody production is not caused by the lack of Treg cells but by a defect in activation-induced cell death that leads to the accumulation of T effector cells that are resistant to regulatory T cell activity.
We evaluated the effects of vitamin and mineral supplementation (from pre-breeding to day 83 of gestation) and two rates of gain (from breeding to day 83 of gestation) on trace mineral concentrations ...in maternal and fetal liver, fetal muscle, and allantoic (ALF) and amniotic (AMF) fluids. Crossbred Angus heifers (n = 35; BW = 359.5 ± 7.1 kg) were randomly assigned to one of two vitamin and mineral supplementation treatments (VMSUP; supplemented (VTM) vs. unsupplemented (NoVTM)). The VMSUP factor was initiated 71 to 148 d before artificial insemination (AI), allowing time for the mineral status of heifers to be altered in advance of breeding. The VTM supplement (113 g·heifer−1·d−1) provided macro and trace minerals and vitamins A, D, and E to meet 110% of the requirements specified by the NASEM, and the NoVTM supplement was a pelleted product fed at a 0.45 kg·heifer−1·day−1 with no added vitamin and mineral supplement. At AI, heifers were assigned to one of two rates of gain treatments (GAIN; low gain (LG) 0.28 kg/d or moderate gain (MG) 0.79 kg/d) within their respective VMSUP groups. On d 83 of gestation fetal liver, fetal muscle, ALF, and AMF were collected. Liver biopsies were performed prior to VMSUP factor initiation, at the time of AI, and at the time of ovariohysterectomy. Samples were analyzed for concentrations of Se, Cu, Zn, Mo, Mn, and Co. A VMSUP × GAIN × day interaction was present for Se and Cu (p < 0.01 and p = 0.02, respectively), with concentrations for heifers receiving VTM being greater at AI and tissue collection compared with heifers not receiving VTM (p < 0.01). A VMSUP × day interaction (p = 0.01) was present for Co, with greater (p < 0.01) concentrations for VTM than NoVTM at the time of breeding. VTM-MG heifers had greater concentrations of Mn than all other treatments (VMSUP × GAIN, p < 0.01). Mo was greater (p = 0.04) for MG than LG, while Zn concentrations decreased throughout the experiment (p < 0.01). Concentrations of Se (p < 0.01), Cu (p = 0.01), Mn (p = 0.04), and Co (p = 0.01) were greater in fetal liver from VTM than NoVTM. Mo (p ≤ 0.04) and Co (p < 0.01) were affected by GAIN, with greater concentrations in fetal liver from LG than MG. In fetal muscle, Se (p = 0.02) and Zn (p < 0.01) were greater for VTM than NoVTM. Additionally, Zn in fetal muscle was affected by GAIN (p < 0.01), with greater concentrations in LG than MG. The ALF in VTM heifers (p < 0.01) had greater Se and Co than NoVTM. In AMF, trace mineral concentrations were not affected (p ≥ 0.13) by VMSUP, GAIN, or their interaction. Collectively, these data suggest that maternal nutrition pre-breeding and in the first trimester of gestation affects fetal reserves of some trace minerals, which may have long-lasting impacts on offspring performance and health.
The effect of early gestation maternal undernutrition followed by realimentation on placentomal vascular growth and angiogenic factor expression was determined in multiparous beef cows bred to the ...same bull. Cows gestating only female fetuses (n = 30) were fed in equal numbers to meet the NRC requirements (control) or were fed below the NRC requirements to lose BW (nutrient restricted; NR) from d 30 to 125 of gestation. After slaughter on d 125 of gestation, 10 control and 10 NR cows were necropsied. The remaining NR cows (n = 5) were then fed to achieve a BCS equal to their control group contemporaries (n = 5) by d 220 of gestation. All cows were fed the control diet from d 220 until 250 of gestation, when the remaining control and NR cows were slaughtered and necropsied. At necropsy, placentomes were fixed via perfusion of the caruncular and cotyledonary arteries to determine capillary vascular density. Cotyledonary (fetal placental) and caruncular (maternal placental) tissues also were snap-frozen in liquid nitrogen, and mRNA concentrations of vascular endothelial growth factor and its 2 specific receptors, fms-like tyrosine kinase and kinase insert domain containing receptor, as well as placental growth factor, were determined. There was no effect of diet or day of gestation on the percentage of proliferating caruncular cells. Although diet did not impact cotyledonary cellular proliferation, there was an increase (P < 0.05) in the percentage of proliferating cells on d 250 compared with d 125 of gestation. Nutrient restriction from d 30 to 125 increased (P <= 0.10) placental mRNA concentrations of placental growth factor and fms-like tyrosine kinase; however, there was no alteration in vascularity. By d 250 of gestation, NR cows had increased (P < 0.05) caruncular capillary surface density and decreased (P < 0.05) cotyledonary capillary area density, capillary number density, and capillary surface density compared with control cows. Although nutrient restriction had little effect on placental vascularity by d 125, upon realimentation, alterations in vascularity became apparent by d 250 of gestation, suggesting a placental programming effect.
To determine the effects of maternal Se intake and plane of nutrition during midgestation, late gestation, or both on hormone and metabolite concentrations in the dam and on placental ...characteristics, pregnant ewe lambs (n = 64) were assigned to 1 of 8 treatments arranged in a 2 x 2 x 2 factorial array: Se level initiated at breeding; adequate (3.05 μg/kg of BW) or high (70.4 μg/kg of BW) and nutritional level 100% (control) or 60% (restricted) of NRC recommendations fed at different times of gestation d 50 to 90 (midgestation) or d 91 to 130 (late gestation). The control ewes had a greater (P = 0.01) percentage change in BW from d 50 than restricted ewes during both mid- and late gestation. Although blood urea N was not affected by either Se or nutritional level, restricted ewes had greater (P = 0.01) concentrations of circulating Se on d 66, 78, 106, 120, and 130 of gestation compared with control ewes. Both Se and timing of the nutritional level affected circulating progesterone; however, only nutritional level affected thyroxine and triiodothyronine concentrations in the dam. Nutrient restriction during late gestation decreased (P less-than or equal to 0.01) fetal BW and fetal fluid weight compared with the control ewes (3.75 vs. 4.13 ± 0.10 kg and 1.61 vs. 2.11 ± 0.11 kg). Although neither Se nor nutritional level affected (P ≥ 0.1) placental, caruncular, or cotyledonary weights, cotyledonary cellular proliferation was decreased (P < 0.05) in ewes receiving a high concentration of Se compared with those receiving adequate Se. In addition, either Se or nutritional level affected vascular endothelial growth factor (VEGFA), VEGFA-receptor 1, VEGFA-receptor 2, and NO synthase mRNA abundance in the cotyledonary tissue. In the caruncular tissue, either Se or nutritional level affected VEGFA-receptor 1, placental growth factor, and NO synthase mRNA abundance. Selenium supplementation and the duration or timing of nutrient restriction appear to influence the endocrine and metabolic status of the ewe, which may influence nutrient transport and placental function.
The objectives were to evaluate effects of maternal nutrient restriction and stage of gestation on maternal and fetal visceral organ mass and indices of jejunal growth and vascularity in beef cows. ...Thirty multiparous beef cows (BW = 571 ± 63 kg; BCS = 5.4 ± 0.7) carrying female fetuses (d 30 of gestation) were allocated to receive a diet of native grass hay (CON; 12.1% CP, 70.7% IVDMD, DM basis) to meet NRC recommendations for BW gain during early gestation or a nutrient-restricted diet of millet straw (NR; 9.9% CP, 54.5% IVDMD, DM basis) to provide 68.1% of NEm and 86.7% of MP estimated requirements. On d 125 of gestation, 10 CON and 10 NR cows were killed and necropsied. Five remaining CON cows received the CON diet, and 5 NR cows were realimented with a concentrate supplement (13.2% CP, 77.6% IVDMD, DM basis) and the CON hay to achieve a BCS similar to CON cows by d 220 of gestation. Remaining cows were necropsied on d 245 of gestation. Cow BW and eviscerated BW (EBW) were less (P < 0.01) for NR than CON at d 125 but did not differ (P > 0.63) at d 245. Cows fed the CON diet had greater (P < 0.09) total gastrointestinal (GI) tract, omasal, and pancreatic weights. Stomach complex, ruminal, and liver weights were greater for CON than NR cows (P < 0.09) on d 125. Total GI, stomach complex, and pancreatic weights increased (P < 0.001) with day of gestation. Restricted cows had decreased (P = 0.09) duodenal RNA:DNA compared with CON. Duodenal DNA was less (P = 0.01) and jejunal RNA:DNA (P = 0.09) was greater for cows at d 125 vs. 245. Cow jejunal capillary area density increased with day of gestation (P = 0.02). Fetal BW and EBW were unaffected by dietary treatment (P ≥ 0.32). Total GI tract and all components increased in mass with day of gestation (P < 0.001). Fetuses from NR dams had greater (P = 0.003) reticular mass at d 245 than CON fetuses. Fetuses from NR cows had greater (P = 0.02) percent jejunal proliferation at d 125 and greater (P = 0.03) total intestinal vascularity (mL) at d 245. Fetal jejunal DNA decreased (P = 0.09), RNA:DNA increased (P = 0.05), and total jejunal proliferating cells increased (P < 0.001) with day of gestation. Jejunal capillary area density, number density, and surface density were greater (P < 0.008) during late gestation. Results indicate that maternal and fetal intestines undergo changes during gestation, which can be affected by nutrient restriction and may partially explain differences observed in fetal development and postnatal performance.
To support the assessments of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES), the IPBES Expert Group on Scenarios and Models is carrying out an ...intercomparison of biodiversity and ecosystem services models using harmonized scenarios (BES-SIM). The goals of BES-SIM are (1) to project the global impacts of land-use and climate change on biodiversity and ecosystem services (i.e., nature's contributions to people) over the coming decades, compared to the 20th century, using a set of common metrics at multiple scales, and (2) to identify model uncertainties and research gaps through the comparisons of projected biodiversity and ecosystem services across models. BES-SIM uses three scenarios combining specific Shared Socio-economic Pathways (SSPs) and Representative Concentration Pathways (RCPs) – SSP1xRCP2.6, SSP3xRCP6.0, SSP5xRCP8.6 – to explore a wide range of land-use change and climate change futures. This paper describes the rationale for scenario selection, the process of harmonizing input data for land use, based on the second phase of the Land Use Harmonization Project (LUH2), and climate, the biodiversity and ecosystem services models used, the core simulations carried out, the harmonization of the model output metrics, and the treatment of uncertainty. The results of this collaborative modeling project will support the ongoing global assessment of IPBES, strengthen ties between IPBES and the Intergovernmental Panel on Climate Change (IPCC) scenarios and modeling processes, advise the Convention on Biological Diversity (CBD) on its development of a post-2020 strategic plans and conservation goals, and inform the development of a new generation of nature-centred scenarios.
To investigate the effects of nutritional plane and Se supply during gestation on ewe and offspring performance and body composition, 84 Rambouillet ewe lambs (age = 240 +/- 17 d, BW = 52.1 +/- 6.2 ...kg) were allocated to a 2 x 3 x 2 factorial arrangement of treatments. Factors included Se adequate Se (ASe, 11.5 microg/kg of BW) or high Se (HSe, 77.0 microg/kg of BW) initiated at breeding, nutritional plane 60% (restricted, RES), 100% (control, CON), or 140% (high, HIH) of NRC requirements initiated at d 40 of gestation, and physiological stage at necropsy 3 to 24 h postpartum or d 20 of lactation. Ewes were fed and housed individually in a temperature-controlled facility. At parturition, all lambs were removed and artificially reared until necropsy on d 20.6 +/- 0.9 of age. Ewes assigned to the treatment at d 20 of lactation were transitioned to a common diet meeting lactation requirements and were mechanically milked. From d 95 of gestation through parturition and d 20 of lactation, ewe BW and BCS were least (P <or= 0.01) in the RES treatment, intermediate in the CON treatment, and greatest in the HIH treatment. Ewes fed HSe had a greater (P <or= 0.05) BCS increase than those fed ASe during mid- and late gestation. During gestation, ewes in the HIH treatment had the greatest (P < 0.001) ADG and G:F, those in the CON treatment were intermediate, and those in the RES treatment were least, whereas ewes fed HSe had greater (P < 0.001) ADG and G:F than those fed ASe during midgestation. Ewe backfat and LM area on d 135 of gestation were least (P < 0.001) in the RES treatment, intermediate in the CON treatment, and greatest in the HIH treatment, with ewes fed HSe having greater (P <or= 0.03) backfat than those fed ASe. During the first 20 d of lactation, ewes fed the RES diet had greater (P < 0.09) G:F than those fed the CON and HIH diets. Physiological stage had no effect on ewe omental and mesenteric fat or perirenal fat weights, although both were greater (P < 0.001) for ewes fed the HIH diet than for those fed the RES and CON diets. At birth, lambs born to ewes in the RES group weighed less and had decreased curved crown rump lengths (P = 0.08) compared with those born to ewes in the CON and HIH groups, and lambs from ewes in the ASe-RES treatment were lighter (P < 0.08) than those from ewes in the HSe-RES, ASe-CON, and ASe-HIH treatments. Lambs from dams in the RES group had less (P < 0.05) BW from d 7 to 19 and decreased (P < 0.07) overall ADG compared with lambs from dams in the CON and HIH groups. Additionally, lambs from dams in the RES group had less (P <or= 0.08) perirenal fat than their counterparts, and lambs from dams in the HIH group had greater (P = 0.01) omental and mesenteric fat than lambs from dams in the RES group. Postpartum serum Se of ewes and lambs (birth and d 19) was increased (P < 0.001) by HSe feeding during gestation. Results indicate that BW differences in pregnant ewes attributable to nutritional plane are accompanied by changes in body composition and offspring BW, both of which may be affected by Se supply.
The effect of vitamins and minerals supplementation (VTM) and/or two rates of body weight gain (GAIN) on bovine placental vascular development and angiogenic factors gene expression were evaluated in ...two experiments: In Exp. 1, crossbred Angus heifers (
= 34) were assigned to VTM/NoVTM treatments at least 71 days before breeding to allow changes in the mineral status. At breeding, through artificial insemination (AI), heifers were assigned to low-gain (LG) 0.28 kg/d or moderate-gain (MG) 0.79 kg/d treatments, resulting in NoVTM-LG (Control;
= 8), NoVTM-MG (
= 8), VTM-LG (
= 9), and VTM-MG (
= 9) until day 83 of gestation; In Exp. 2, crossbred angus heifers (
= 28), were assigned to control (CON;
= 12), receiving a basal total mixed ration (TMR) or TMR + VTM (VTM;
= 16) from breeding until parturition. Placentomes from Exp. 1 and cotyledons (COT) from Exp. 2 were evaluated by immunohistochemistry for COT vascular density area. COTs from Exp. 1 were evaluated for angiogenic factor (
-1,
-2,
2,
3,
1,
,
,
) gene expression. In Exp. 1, COT vascularity was not affected by the interaction of VTM and GAIN (
= 0.67) or the main effects of VTM (
= 0.50) and GAIN (
= 0.55). Likewise, angiogenic factors were not differentially expressed between treatments (
< 0.05). In Exp. 2, COT vascularity was greater in VTM vs. CON (
= 0.07). In conclusion, there is a suggested later-stage influence of vitamin and mineral supplementation on placental vascularity, emphasizing the importance of supplementation beyond early pregnancy.
In mammals, two types of adipose tissues are present, brown (BAT) and white (WAT). WAT itself can be divided into subcutaneous and internal fat deposits. All these tissues have been shown to present ...a great tissue plasticity, and recent data emphasized on the multiple differentiation potentials obtained from subcutaneous WAT. However, no study has compared the heterogeneity of stroma-vascular fraction (SVF) cells and their differentiation potentials according to the localization of the fat pad. This study clearly demonstrates that WAT and BAT present different antigenic features and differentiation potentials. WAT by contrast to BAT contains a large population of hematopoietic cells composed essentially of macrophages and hematopoietic progenitor cells. In WAT, the non-hematopoietic population is mainly composed of mesenchymal stem cell (MSC)-like but contains also a significant proportion of immature cells, whereas in BAT, the stromal cells do not present the same phenotype. Internal and subcutaneous WAT present some discrete differences in the phenotype of their cell populations. WAT derived SVF cells give rise to osteoblasts, endothelial cells, adipocytes, hematopoietic cells, and cardiomyoblasts only from inguinal cells. By contrast, BAT derived SVF cells display a reduced plasticity. Adipose tissues thus appear as complex tissues composed of different cell subsets according to the location of fat pads. Inguinal WAT appears as the most plastic adipose tissue and represents a potential and suitable source of stem cell, considering its easy sampling as a major advantage for cell therapy.
Phenotypic evidence indicates that the ability to taste the bitter compounds phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) may protect against cigarette smoking. In this study, PTC gene ...haplotypes were found to be associated with both the odds of being a smoker and the importance of cigarette taste as a smoking motive. Smokers (n = 384) and nonsmokers (n = 183) were genotyped for polymorphisms that affect taste sensitivity to PTC and PROP. The "taster" PAV haplotype, relative to the "nontaster" AVI haplotype, was predicted to be associated with reduced odds of being a smoker and lower taste motivation as measured by the Wisconsin Inventory of Smoking Dependence Motives-68 taste/sensory processes scale. The results did not support the predicted association between the PAV and AVI haplotypes and smoker odds, but the AAV haplotype, which confers intermediate PTC/PROP taste sensitivity, was associated with reduced smoker prevalence (49% vs. 70%), chi(2)(1, N = 567) = 10.392, p = .001. The predicted relationship between PAV and AVI and taste motivation was found, F(2, 348) = 3.303, p = .038. The results encourage further exploration of the role of taste/sensory processes in tobacco dependence.
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