Wet Angrites? A D/H and Pb-Pb Study of Silicates and Phosphates

No abstract availabl

Introduction of Macromolecules into Bovine Adrenal Medullary Chromaffin Cells and Rat Pheochromocytoma Cells (PC12) by Permeabilization with Streptolysin O: Inhibitory Effect of Tetanus Toxin on Catecholamine Secretion

Conditions are described for controlled plasma membrane permeabilization of rat pheochromocytoma cells (PC12) and cultured bovine adrenal chromaffin cells by Streptolysin O (SLO). The transmembrane pores created by SLO invoke rapid efflux of intracellular 86Rb+ and ATP, and also permit passive diffusion of proteins, including immunoglobulins, into the cells. SLO-permeabilized PC12 cells release [3H]dopamine in response to micromolar concentrations of free Ca2+. Permeabilized adrenal chromaffin cells present a similar exocytotic response to Ca2+ in the presence of Mg2+/ ATP. Permeabilized PC12 cells accumulate antibodies against synaptophysin and calmodulin, but neither antibody reduces the Ca2+-dependent secretory response. Reduced tetanus toxin, although ineffective when applied to intact chromaffin cells, inhibits Ca2+-induced exocytosis by both types of permeabilized cells studied. Omission of dithiothreitol, toxin inactivation by boiling, or preincubation with neutralizing antibodies abolishes the inhibitory effect. The data indicate that plasma membrane permeabilization by Streptolysin O is a useful tool to probe and define cellular components that are involved in the final steps of exocytosis

Between a hygiene rock and a hygienic hard place:Avoiding SARS-CoV-2 while needing environmental exposures for immunity

Suboptimal understanding of concepts related to hygiene by the general public, clinicians and researchers is a persistent problem in health and medicine. Although hygiene is necessary to slow or prevent deadly pandemics of infectious disease such as coronavirus disease 2019 (COVID-19), hygiene can have unwanted effects. In particular, some aspects of hygiene cause a loss of biodiversity from the human body, characterized by the almost complete removal of intestinal worms (helminths) and protists. Research spanning more than half a century documents that this loss of biodiversity results in an increased propensity for autoimmune disease, allergic disorders, probably neuropsychiatric problems and adverse reactions to infectious agents. The differences in immune function between communities with and communities without helminths have become so pronounced that the reduced lethality of severe acute respiratory syndrome coronavirus 2 in low-income countries compared to high-income countries was predicted early in the COVID-19 pandemic. This prediction, based on the maladaptive immune responses observed in many cases of COVID-19 in high-income countries, is now supported by emerging data from low-income countries. Herein, hygiene is subdivided into components involving personal choice versus components instituted by community wide systems such as sewage treatment facilities and water treatment plants. The different effects of personal hygiene and systems hygiene are described, and appropriate measures to alleviate the adverse effects of hygiene without losing the benefits of hygiene are discussed. Finally, text boxes are provided to function as stand-alone, public-domain handouts with the goal of informing the public about hygiene and suggesting solutions for biomedical researchers and policy makers. Lay Summary: Hygiene related to sewer systems and other technology can have adverse effects on immune function, and is distinct from personal hygiene practices such as hand washing and social distancing. Dealing with the drawbacks of hygiene must be undertaken without compromising the protection from infectious disease imposed by hygiene

Gene Expression Changes Associated with the Airway Wall Response to Injury

Understanding the way in which the airway heals in response to injury is fundamental to dissecting the mechanisms underlying airway disease pathology. As only limited data is available in relation to the in vivo characterisation of the molecular features of repair in the airway we sought to characterise the dynamic changes in gene expression that are associated with the early response to physical injury in the airway wall.We profiled gene expression changes in the airway wall using a large animal model of physical injury comprising bronchial brush biopsy in anaesthetised sheep. The experimental design featured sequential studies in the same animals over the course of a week and yielded data relating to the response at 6 hours, and 1, 3 and 7 days after injury. Notable features of the transcriptional response included the early and sustained preponderance of down-regulated genes associated with angiogenesis and immune cell activation, selection and differentiation. Later features of the response included the up-regulation of cell cycle genes at d1 and d3, and the latter pronounced up-regulation of extracellular matrix-related genes at d3 and d7.It is possible to follow the airway wall response to physical injury in the same animal over the course of time. Transcriptional changes featured coordinate expression of functionally related genes in a reproducible manner both within and between animals. This characterisation will provide a foundation against which to assess the perturbations that accompany airway disease pathologies of comparative relevance

Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women

Microbiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes. In obese subjects, gradual weight loss ameliorates adipose tissue inflammation and related systemic changes. We assessed how rapid weight loss due to a very low calorie diet (VLCD) affects the fecal microbiome and fecal bile acid composition, and their interactions with the plasma metabolome and subcutaneous adipose tissue inflammation in obesity. We performed a prospective cohort study of VLCD-induced weight loss of 10% in ten grades 2-3 obese postmenopausal women in a metabolic unit. Baseline and post weight loss evaluation included fasting plasma analyzed by mass spectrometry, adipose tissue transcription by RNA sequencing, stool 16S rRNA sequencing for fecal microbiota, fecal bile acids by mass spectrometry, and urinary metabolic phenotyping by H-NMR spectroscopy. Outcome measures included mixed model correlations between changes in fecal microbiota and bile acid composition with changes in plasma metabolite and adipose tissue gene expression pathways. Alterations in the urinary metabolic phenotype following VLCD-induced weight loss were consistent with starvation ketosis, protein sparing, and disruptions to the functional status of the gut microbiota. We show that the core microbiome was preserved during VLCD-induced weight loss, but with changes in several groups of bacterial taxa with functional implications. UniFrac analysis showed overall parallel shifts in community structure, corresponding to reduced abundance of the genus Roseburia and increased Christensenellaceae;g__ (unknown genus). Imputed microbial functions showed changes in fat and carbohydrate metabolism. A significant fall in fecal total bile acid concentration and reduced deconjugation and 7-α-dihydroxylation were accompanied by significant changes in several bacterial taxa. Individual bile acids in feces correlated with amino acid, purine, and lipid metabolic pathways in plasma. Furthermore, several fecal bile acids and bacterial species correlated with altered gene expression pathways in adipose tissue. VLCD dietary intervention in obese women changed the composition of several fecal microbial populations while preserving the core fecal microbiome. Changes in individual microbial taxa and their functions correlated with variations in the plasma metabolome, fecal bile acid composition, and adipose tissue transcriptome

IMMUNE RESPONSE IN MALIGNANT GLIOMA

Objective: Malignant gliomas are primary brain tumors with excessive mortality and high resistance to chemotherapy and radiotherapy. The survival time for glioblastoma multi­forme is about 6-12 months. As key pathogenetic mechanisms are recognized the massive necrosis, angiogenesis and hypoxia within the tumor, as well as the resistance to apoptosis. It is also suspected that altered immune response might contribute to the fatal clinical outcome.The aim of the present study was to determine the immune status of patients with malignant gliomas.Material and methods: Peripheral blood lymphocytes were collected preoperatively from 9 patients (aged 57-76) diagnosed as anaplastic astrocytoma grade III (n=4) and glioblastoma multiforme (n=5). The following lymphocyte populations were analyzed by flow cytometry: CD19+, CD3+, CD3+CD4+, CD3+CD8+, CD3-CD56+, CD3+CD56+, CD3+CD25+, CD8-CD11b+, CD8+CD11b+, CD8+CD11b-. The results obtained were compared to reference values for each cell population.Results: No significant alterations were detected in CD19+, CD3+, CD3+CD4+, CD3+CD8+ cells, but the CD4/CD8 ratio was below the reference range in some cases. No obvious decrease in (CD3-CD56+) NK cells and (CD3-CD56+) NKT cells was observed in most patients. A reproducible phenomenon of increased CD8+CD11b+ and decreased CD8+CD11b- cells was noticed. These preliminary results suggest that the immune response in patients with malignant glioma is seriously disregulated. The rapid clinical deterioration, relapses and high mortality could be at least partially explained with the suppressed activity of NK-cells which are the major cytotoxic antitumoral cells. The increase in the population of activated suppressor-effector cells also contributes to the unfavourable outcome in malignant brain tumors.Conclusion: This pilot study reveals the presence of altered immune response in malignant gliomas and opens possibilities for prospective investigations concerning immune status and clinical outcome

Width of the Δ\Delta resonance in nuclei

In this work we evaluate the imaginary part of the isobar $\Delta$ self-energy $\Sigma_{\Delta}$ from the two-body absorption process $\Delta+N\rightarrow 2N$. This contribution is calculated using a recently developed non-relativistic scheme, which allows for an evaluation of the self-energy with a basis of single-particle states appropriate for both bound hole states and for particle states in the continuum. In order to test the medium dependence of the self-energy, we calculate the two-body absorption term $\Sigma_{\Delta}^{A2}$ for several finite nuclei with $N=Z$, i.e.\ $^{16}$O, $^{40}$Ca and $^{100}$Sn. The resulting self-energy, which is energy dependent and non-local, is compared with a simple parameterization derived from nuclear matter.Comment: 5 pages 3 figures can be obtained from the authors, TU-93-160

Studies of a genetic variant in HK1 in relation to quantitative metabolic traits and to the prevalence of type 2 diabetes

Single nucleotide polymorphisms (SNPs) within the gene encoding Hexokinase 1 (HK1) are associated with changes in glycated haemoglobin (HbA1c) levels. Our aim was to investigate the effect of HK1 rs7072268 on measures of glucose- and lipid-metabolism in a Danish non-diabetic population and combine the outcome of these analyses in a meta-analysis with previously published results. Furthermore, our aim was to perform a type 2 diabetes case-control analysis and meta-analysis with two previous case-control studies