"Tolerization" of human T-helper cell clones by chronic exposure to alloantigen

Induction of clonal anergy in T-helper (Th) cells may have a role in regulating immune responses. A model system for studying Th cell tolerization at the clonal level in vitro could be useful for investigating the mechanisms involved. Accordingly, alloreactive helper cells were maintained in culture with interleukin 2 (IL 2) by intermittent stimulation with specific antigen. Regardless of the frequency of antigen stimulation, clones of age less than ca. 35 population doublings (PD) were found to undergo antigen-specific autocrine clonal expansion in the absence of exogenous IL 2. Such young clones (designated as phase I) could therefore not be "tolerized" by frequent exposure to antigen. In contrast, most clones of age greater than ca. 35 PD could be tolerized by frequent exposure to antigen (designated as phase II clones). Their autocrine proliferation was then blocked, although they still recognized antigen specifically as shown by their retained ability to secrete interferon-gamma (IFN-gamma) and granulocyte-macrophage colony stimulating factor (GM-CSF). The mechanism of response failure involved both an inability to upregulate IL 2 receptors in the absence of exogenous IL 2, as well as an inability to secrete IL 2. These defects were not overcome by stimulation with mitogens or calcium ionophore and phorbol esther in place of alloantigen. T-cell receptor, alpha, beta, and gamma-chain gene rearrangements remained identical in phase I and phase II clones. Tolerization of phase II clones could be avoided by increasing the period between antigen exposures. Despite this, whether or not phase II cells were capable of autocrine proliferation, they were found to have acquired the novel function of inducing suppressive activity in fresh lymphocytes. Suppressor-induction was blocked by the broadly reactive MHC class II-specific monoclonal antibody (moAb) TU39, but not by moAb preferentially reacting only with HLA-DR, DQ, or DP. Sequential immunoprecipitation on T-cell clones showed the presence of a putative non-DR, DQ, DP, TU39+ molecule on phase II clones. However, this molecule was also found on phase I clones. The nature of the TU39-blockable suppressor-inducing determinant present on phase II but not on (most) phase I clones thus remains to be clarified. In addition to suppressor-induction activity, phase II clones also acquired lytic potential as measured in a lectin approximation system. Cytotoxic (CTX) potential was also not influenced by the frequency of antigenic stimulation and could be viewed as a constitutive modulation of clonal functio

Effectiveness of a group-based psychosocial program to prevent depression and anxiety in older people attending primary health care centres: a randomised controlled trial

Background: Evidence about the effectiveness of psychosocial interventions to reduce the incidence of depression and anxiety and promote subjective well-being in older people is limited, particularly in Latin-American countries. This study thus aims to assess a program specifically designed to address this issue in persons aged 65 to 80 and attending primary health care centres. Method: Older people who use primary care centres are to be randomly assigned to the program or to a control group. Only independent users will be included; those having had a major depressive disorder or an anxiety disorder in the last 6 months will be excluded. The program is group based; it includes cognitive stimulation, expansion of social support networks and cognitive behaviour strategies. Depressive and anxiety symptoms and disorders, as well as psychological well-being, will be assessed using standardised instruments, once before implementing the program and later, after 18 and 36 weeks. Discussion: Primary care is a setting where interventions to improve mental health can be beneficial. Providing evidence-based programs that work with older people is a priority for public mental health

Ince's limits for confluent and double-confluent Heun equations

We find pairs of solutions to a differential equation which is obtained as a special limit of a generalized spheroidal wave equation (this is also known as confluent Heun equation). One solution in each pair is given by a series of hypergeometric functions and converges for any finite value of the independent variable $z$, while the other is given by a series of modified Bessel functions and converges for $|z|>|z_{0}|$, where $z_{0}$ denotes a regular singularity. For short, the preceding limit is called Ince's limit after Ince who have used the same procedure to get the Mathieu equations from the Whittaker-Hill ones. We find as well that, when $z_{0}$ tends to zero, the Ince limit of the generalized spheroidal wave equation turns out to be the Ince limit of a double-confluent Heun equation, for which solutions are provided. Finally, we show that the Schr\"odinger equation for inverse fourth and sixth-power potentials reduces to peculiar cases of the double-confluent Heun equation and its Ince's limit, respectively.Comment: Submitted to Journal of Mathmatical Physic

Fluid flow stimulates chemoautotrophy in hydrothermally influenced coastal sediments

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Sievert, S. M., Buehring, S., Gulmann, L. K., Hinrichs, K.-U., Ristova, P. P., & Gomez-Saez, G. Fluid flow stimulates chemoautotrophy in hydrothermally influenced coastal sediments. Communications Earth & Environment, 3(1), (2022): 96, https://doi.org/10.1038/s43247-022-00426-5.Hydrothermalism in coastal sediments strongly impacts biogeochemical processes and supports chemoautotrophy. Yet, the effect of fluid flow on microbial community composition and rates of chemoautotrophic production is unknown because rate measurements under natural conditions are difficult, impeding an assessment of the importance of these systems. Here, in situ incubations controlling fluid flow along a transect of three geochemically distinct locations at a shallow-water hydrothermal system off Milos (Greece) show that Campylobacteria dominated chemoautotrophy in the presence of fluid flow. Based on injected 13C-labelled dissolved inorganic carbon and its incorporation into fatty acids, we constrained carbon fixation to be as high as 12 µmol C cm−3 d−1, corresponding to areal rates up to 10-times higher than previously reported for coastal sediments, and showed the importance of fluid flow for supplying the necessary substrates to support chemoautotrophy. Without flow, rates were substantially lower and microbial community composition markedly shifted. Our results highlight the importance of fluid flow in shaping the composition and activity of microbial communities of shallow-water hydrothermal vents, identifying them as hotspots of microbial productivity.Open Access funding enabled and organized by Projekt DEAL

Decreased CD90 expression in human mesenchymal stem cells by applying mechanical stimulation

BACKGROUND: Mesenchymal stem cells (MSC) are multipotent cells which can differentiate along osteogenic, chondrogenic, and adipogenic lineages. The present study was designed to investigate the influence of mechanical force as a specific physiological stress on the differentiation of (MSC) to osteoblast-like cells. METHODS: Human MSC were cultured in osteoinductive medium with or without cyclic uniaxial mechanical stimulation (2000 μstrain, 200 cycles per day, 1 Hz). Cultured cells were analysed for expression of collagen type I, osteocalcin, osteonectin, and CD90. To evaluate the biomineral formation the content of bound calcium in the cultures was determined. RESULTS: After 14 days in culture immunfluorescence staining revealed enhancement of collagen type I and osteonectin expression in response to mechanical stimulation. In contrast, mechanically stimulated cultures stained negative for CD90. In stimulated and unstimulated cultures an increase in the calcium content over time was observed. After 21 days in culture the calcium content in mechanical stimulated cultures was significantly higher compared to unstimulated control cultures. CONCLUSION: These results demonstrate the influence of mechanical force on the differentiation of human MSC into osteoblast-like cells in vitro. While significant enhancement of the biomineral formation by mechanical stimulation is not detected before 21 days, effects on the extracellular matrix became already obvious after 14 days. The decrease of CD90 expression in mechanically stimulated cultures compared to unstimulated control cultures suggests that CD90 is only transiently expressed expression during the differentiation of MSC to osteoblast-like cells in culture

On the sedimentological origin of down-core variations of bulk sedimentary nitrogen isotope ratios

Author Posting. © American Geophysical Union, 2005. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 20 (2005): PA2009, doi:10.1029/2004PA001081.The bulk sedimentary nitrogen isotopic composition of two cores from nearby sites on the northern slope of the South China Sea (Site 17940 and Ocean Drilling Program (ODP) Site 1144) differs by up to >2‰ during the last glacial period. Given their close proximity, both core sites are located in the same biogeographic zone and nutrient regime, and it is thus unlikely that this offset is due to a true gradient in surface ocean conditions. In an attempt to resolve this offset, we have investigated the possible effects of two sedimentological parameters that can affect bulk sedimentary δ15N, namely, the variable contribution of inorganic N to bulk N in the sediment and the grain-size dependence of bulk δ15N. We find that neither effect, singly or in combination, is sufficient to explain the significant δ15N offset between the two down-core records. By elimination the most likely explanation for the observed discrepancy is a different origin of both the organic and inorganic nitrogen at each site. This study adds to the growing body of evidence highlighting the complex nature and origin of the sedimentary components in sediment drifts, such as ODP Site 1144.Funding from NSERC Canada (to S.E.C. and M.K.) and NSF (OCE-0214365 and OCE-0318371 to M.J.H. and OCE-0327405 to T.I.E.) is gratefully acknowledged, as well as Woods Hole Oceanographic Institution Postdoctoral Fellowships (M.K. and G.M.), the Camille and Henry Dreyfus Postdoctoral Program in Environmental Chemistry (M.J.H.), and a Geological Society of America student research grant (M.K.)

Mesodermal Progenitor Cells (MPCs) Differentiate into Mesenchymal Stromal Cells (MSCs) by Activation of Wnt5/Calmodulin Signalling Pathway

Mesenchymal Stromal Cells (MSCs) remain poorly characterized because of the absence of manifest physical, phenotypic, and functional properties in cultured cell populations. Despite considerable research on MSCs and their clinical application, the biology of these cells is not fully clarified and data on signalling activation during mesenchymal differentiation and proliferation are controversial. The role of Wnt pathways is still debated, partly due to culture heterogeneity and methodological inconsistencies. Recently, we described a new bone marrow cell population isolated from MSC cultures that we named Mesodermal Progenitor Cells (MPCs) for their mesenchymal and endothelial differentiation potential. An optimized culture method allowed the isolation from human adult bone marrow of a highly pure population of MPCs (more than 97%), that showed the distinctive SSEA-4+CD105+CD90(neg) phenotype and not expressing MSCA-1 antigen. Under these selective culture conditions the percentage of MSCs (SSEA-4(neg)CD105+CD90(bright) and MSCA-1+), in the primary cultures, resulted lower than 2%.We demonstrate that MPCs differentiate to MSCs through an SSEA-4+CD105+CD90(bright) early intermediate precursor. Differentiation paralleled the activation of Wnt5/Calmodulin signalling by autocrine/paracrine intense secretion of Wnt5a and Wnt5b (p<0.05 vs uncondictioned media), which was later silenced in late MSCs (SSEA-4(neg)). We found the inhibition of this pathway by calmidazolium chloride specifically blocked mesenchymal induction (ID₅₀ =  0.5 µM, p<0.01), while endothelial differentiation was unaffected.The present study describes two different putative progenitors (early and late MSCs) that, together with already described MPCs, could be co-isolated and expanded in different percentages depending on the culture conditions. These results suggest that some modifications to the widely accepted MSC nomenclature are required

Benthic pH gradients across a range of shelf sea sediment types linked to sediment characteristics and seasonal variability

This study used microelectrodes to record pH profiles in fresh shelf sea sediment cores collected across a range of different sediment types within the Celtic Sea. Spatial and temporal variability was captured during repeated measurements in 2014 and 2015. Concurrently recorded oxygen microelectrode profiles and other sedimentary parameters provide a detailed context for interpretation of the pH data. Clear differences in profiles were observed between sediment type, location and season. Notably, very steep pH gradients exist within the surface sediments (10–20 mm), where decreases greater than 0.5 pH units were observed. Steep gradients were particularly apparent in fine cohesive sediments, less so in permeable sandier matrices. We hypothesise that the gradients are likely caused by aerobic organic matter respiration close to the sediment–water interface or oxidation of reduced species at the base of the oxic zone (NH4+, Mn2+, Fe2+, S−). Statistical analysis suggests the variability in the depth of the pH minima is controlled spatially by the oxygen penetration depth, and seasonally by the input and remineralisation of deposited organic phytodetritus. Below the pH minima the observed pH remained consistently low to maximum electrode penetration (ca. 60 mm), indicating an absence of sub-oxic processes generating H+ or balanced removal processes within this layer. Thus, a climatology of sediment surface porewater pH is provided against which to examine biogeochemical processes. This enhances our understanding of benthic pH processes, particularly in the context of human impacts, seabed integrity, and future climate changes, providing vital information for modelling benthic response under future climate scenarios

The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis

BACKGROUND: The chemokine stromal derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 have been demonstrated to be crucial for the homing of stem cells and prostate cancers to the marrow. While screening prostate cancers for CXCL12-responsive adhesion molecules, we identified CD164 (MGC-24) as a potential regulator of homing. CD164 is known to function as a receptor that regulates stem cell localization to the bone marrow. RESULTS: Using prostate cancer cell lines, it was demonstrated that CXCL12 induced both the expression of CD164 mRNA and protein. Functional studies demonstrated that blocking CD164 on prostate cancer cell lines reduced the ability of these cells to adhere to human bone marrow endothelial cells, and invade into extracellular matrices. Human tissue microarrays stained for CD164 demonstrated a positive correlation with prostate-specific antigen levels, while its expression was negatively correlated with the expression of androgen receptor. CONCLUSION: Our findings suggest that CD164 may participate in the localization of prostate cancer cells to the marrow and is further evidence that tumor metastasis and hematopoietic stem cell trafficking may involve similar processes