Development of cell surface saccharides on embryonic pancreatic cells

Using a battery of seven lectin-ferritin conjugates as probes for cell surface glycoconjugates, we have studied the pattern of plasmalemmal differentiation of cells in the embryonic rat pancreas from day 15 in utero to the early postpartum stage. Our results indicate that differentiation of plasmalemmal glycoconjugates on acinar, endocrine, and centroacinar cells is temporally correlated with development and is unique for each cell type, as indicated by lectin-ferritin binding. Specifically, (a) expression of adult cell surface saccharide phenotype can be detected on presumptive acinar cells as early as 15 d in utero, as indicated by soybean agglutinin binding, and precedes development of intracellular organelles characteristic of mature acinar cells; (b) maturation of the plasmalemma of acinar cells is reached after intracellular cytodifferentiation is completed, as indicated by appearance of Con A and fucoselectin binding sites only at day 19 of development; conversely, maturation of the endocrine cell plasmalemma is accompanied by "loss" (masking) of ricinus communis II agglutinin receptors; and (c) binding sites for fucose lectins and for soybean agglutinin are absent on endocrine and centroacinar cells at all stages examined. We conclude that acinar, centroacinar, and endocrine cells develop from a common progenitor cell(s) whose plasmalemmal carbohydrate composition resembles most closely that of the adult centroacinar cell. Finally, appearance of acinar lumina beginning at approximately 17 d in utero is accompanied by differenetiation of apical and basolateral plasmalemmal domains of epithelial cells, as indicated by enhanced binding of several lectin-ferritin conjugates to the apical plasmalemmal, a pattern that persists from this stage through adult life.     

Increased graft-versus-host response of parental-strain (donor) lymphoid cells in cyclophosphamide-treated F1 recipients.

Cyclophosphamide (CY) treatment of F₁ hybrid mice increases their susceptibility to attack by parental-strain lymphoid cells. The donor cells may contribute to this increased susceptibility either by a more vigorous response to the host antigens, or by an increase in their colonization of the host's tissues. We have assessed the responsiveness of the donor cells in the CY-treated host through the use of a local graft-versus-host (GVH) assay. This assay is not influenced by changes in the capacity of donor cells to colonize host tissues, and thus colonization has been eliminated as a variable. In this assay donor lymph node tissue is grafted onto the cut surface of host kidney, and a local GVH reaction is indicated by enlargement of the donor tissue. We show that treatment of F₁ hosts with CY (100 mg/kg) 24 hr prior to grafting leads to increased responsiveness of the donor cells as measured by enlargement of the donor tissue.     

Age-Specific Mortality During the 1918 Influenza Pandemic: Unravelling the Mystery of High Young Adult Mortality

The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889–90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics.

“The war is over – and I must go” Egon Schiele, 1890–1918.

     

Virulence and pathogenicity of Candida albicans is enhanced in biofilms containing oral bacteria

This study examined the influence of bacteria on the virulence and pathogenicity of candidal biofilms. Mature biofilms (Candida albicans-only, bacteria-only, C. albicans with bacteria) were generated on acrylic and either analysed directly, or used to infect a reconstituted human oral epithelium (RHOE). Analyses included Candida hyphae enumeration and assessment of Candida virulence gene expression. Lactate dehydrogenase (LDH) activity and Candida tissue invasion following biofilm infection of the RHOE were also measured. Candida hyphae were more prevalent (p < 0.05) in acrylic biofilms also containing bacteria, with genes encoding secreted aspartyl-proteinases (SAP4/SAP6) and hyphal-wall protein (HWP1) up-regulated (p < 0.05). Candida adhesin genes (ALS3/EPA1), SAP6 and HWP1 were up-regulated in mixed-species biofilm infections of RHOE. Multi-species infections exhibited higher hyphal proportions (p < 0.05), up-regulation of IL-18, higher LDH activity and tissue invasion. As the presence of bacteria in acrylic biofilms promoted Candida virulence, consideration should be given to the bacterial component when managing denture biofilm associated candidoses.     

Soil carbon sequestration and land use change associated with biofuel production: empirical evidence

Soil organic carbon (SOC) change can be a major impact of land use change (LUC) associated with biofuel feedstock production. By collecting and analyzing data from worldwide field observations of major LUCs from cropland, grassland, and forest to lands producing biofuel crops (i.e. corn, switchgrass, Miscanthus, poplar, and willow), we were able to estimate SOC response ratios and sequestration rates and evaluate the effects of soil depth and time scale on SOC change. Both the amount and rate of SOC change were highly dependent on the specific land transition. Irrespective of soil depth or time horizon, cropland conversions resulted in an overall SOC gain of 6–14% relative to initial SOC level, while conversion from grassland or forest to corn (without residue removal) or poplar caused significant carbon loss (9–35%). No significant SOC changes were observed in land converted from grasslands or forests to switchgrass, Miscanthus, or willow. The SOC response ratios were similar in both 0–30 and 0–100 cm soil depths in most cases, suggesting SOC changes in deep soil and that use of top soil only for SOC accounting in biofuel life cycle analysis (LCA) might underestimate total SOC changes. Soil carbon sequestration rates varied greatly among studies and land transition types. Generally, the rates of SOC change tended to be the greatest during the 10 years following land conversion and had declined to approach 0 within about 20 years for most LUCs. Observed trends in SOC change were generally consistent with previous reports. Soil depth and duration of study significantly influence SOC change rates and so should be considered in carbon emission accounting in biofuel LCA. High uncertainty remains for many perennial systems and forest transitions, additional field trials, and modeling efforts are needed to draw conclusions about the site‐ and system‐specific rates and direction of change.     

A superposition free method for protein conformational ensemble analyses and local clustering based on a differential geometry representation of backbone

Here a differential geometry (DG) representation of protein backbone is explored on the analyses of protein conformational ensembles. The protein backbone is described by curvature, κ, and torsion, τ, values per residue and we propose 1) a new dissimilarity and protein flexibility measurement and 2) a local conformational clustering method. The methods were applied to Ubiquitin and c-Myb-KIX protein conformational ensembles and results show that κ\τ metric space allows to properly judge protein flexibility by avoiding the superposition problem. The d_max measurement presents equally good or superior results when compared to RMSF, especially for the intrinsically unstructured protein. The clustering method is unique as it relates protein global to local dynamics by providing a global clustering solutions per residue. The methods proposed can be especially useful to the analyses of highly flexible proteins. The software written for the analyses presented here is available at https://github.com/AMarinhoSN/FleXgeo for academic usage only.     

Iron-based phosphorus chelator: Risk of iron deposition and action on bone metabolism in uremic rats

Phosphate chelators are frequently used in patients with chronic kidney disease (CKD). New iron-based chelators remain understudied and offer a promising therapeutic option for the control of bone and mineral disorders of chronic kidney disease (BMD-CKD). We assessed the effect of the phosphorus chelator, chitosan-iron III (CH-FeCl), compared to calcium carbonate (CaCO₃) in BMD-CKD and the potential iron overload in uremic rats. Thirty-two animals were divided into four groups, namely the control, CKD, CKD/CH-FeCl, and CKD/CaCO₃ groups. CKD was induced by adding 0.75% (4 weeks) and 0.1% (3 weeks) adenine to the diet. The chelators were administered from week 3 through week 7. The renal function, BMD-CKD markers, and histomorphometry of the femur were assessed at week 7. The CKD group showed a significant increase in creatinine (83.9 ± 18.6 vs. 41.5 ± 22.1 µmol/L; P = 0.001), phosphate (3.5 ± 0.8 vs. 2.2 ± 0.2 mmol/L; P = 0.001), fractional excretion of phosphorus (FEP) (0.71 ± 0.2 vs. 0.2 ± 0.17; P = 0.0001), and FGF23 (81.36 ± 37.16 pg/mL vs. 7.42 ± 1.96; P = 0.011) compared to the control group. There was no accumulation of serum or bone iron after the use of CH-FeCl. The use of chelators reduced the FEP (control: 0.71 ± 0.20; CKD/CH-FeCl: 0.40 ± 0.16; CKD/CaCO₃ 0.34 ± 0.15; P = 0.001), without changes in the serum FGF23 and parathyroid hormone levels. Histomorphometry revealed the presence of bone disease with high remodeling in the uremic animals without changes with the use of chelators. The CH-FeCl chelator was efficient in reducing the FEP without iron accumulation, thereby paving the way for the use of this class of chelators in clinical settings in the future.