CD8
T cells play a pivotal role in clearing intracellular pathogens and combatting tumours. Upon infection, naïve CD8
T cells differentiate into effector and memory cells, and this program is ...underscored by large-scale and coordinated changes in the chromatin architecture and gene expression. Importantly, recent evidence demonstrates that the epigenetic mechanisms that regulate the capacity for rapid effector function of memory T cells are shared by innate immune cells such as natural killer (NK) cells. Thus, it appears that the crucial difference between innate and adaptive immunity is the presence of the naïve state. This important distinction raises an intriguing new hypothesis, that the naïve state was evolutionary installed to restrain a default program of effector and memory differentiation in response to antigen recognition. We argue that the hallmark of adaptive T immunity is therefore the naïve program, which actively maintains CD8
T cell quiescence until receipt of appropriate activation signals. In this review, we examine the mechanistic control of naïve CD8
T cell quiescence and summarise the multiple levels of restraint imposed in naïve cells in to limit spontaneous and inappropriate activation. This includes epigenetic mechanisms and transcription factor (TF) regulation of gene expression, in addition to novel inhibitory receptors, abundance of RNA, and protein degradation.
In this paper, the thermodynamic configurational force associated with a moving interface is used to derive the conditions for phase growth and nucleation in bodies with multiple diffusing species ...and arbitrary surface stress at the phase interface. First, the mass, momentum and energy balances are derived on the evolving phase interface. The thermodynamic conditions that result from free energy inequality at the interface are derived leading to the analytical form of the configurational force for bodies subject to mechanical loads, heat and multiple diffusing species. The derived second law condition naturally extends the Eshelby energy–momentum tensor to include species diffusion terms. The above second law restriction is then used to derive the condition for the growth of new phases in a body undergoing finite deformation subject to inhomogeneous as well as anisotropic interface stress, and multiple diffusing species. The growth conditions are derived in both current and reference configurations. The statistical temperature-dependent growth velocity is next derived using the Boltzmann distribution. The derived finite deformation form of growth requirement is simplified to obtain the small deformation diffusive void growth condition. Next, a general, finite deformation, arbitrary surface stress form of phase nucleation condition is derived by considering uncertainty in growth of a small nucleus. The probability of nucleation is shown to naturally depend on a theoretical estimate of critical volumetric energy density, which is directly related to the surface stress. The classical nucleation theory is shown to result from a simplified special case of the general criterion. As an application of the developed theory, the classical Blech electromigration experiment is simulated to estimate the critical energy density corresponding to the onset of electromigration voids at Al–TiN interface.
The differentiation of naive CD8+ T lymphocytes into cytotoxic effector and memory CTL results in large-scale changes in transcriptional and phenotypic profiles. Little is known about how large-scale ...changes in genome organization underpin these transcriptional programs. We use Hi-C to map changes in the spatial organization of long-range genome contacts within naive, effector, and memory virus-specific CD8+ T cells. We observe that the architecture of the naive CD8+ T cell genome is distinct from effector and memory genome configurations, with extensive changes within discrete functional chromatin domains associated with effector/memory differentiation. Deletion of BACH2, or to a lesser extent, reducing SATB1 DNA binding, within naive CD8+ T cells results in a chromatin architecture more reminiscent of effector/memory states. This suggests that key transcription factors within naive CD8+ T cells act to restrain T cell differentiation by actively enforcing a unique naive chromatin state.
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•CD8+ T cell differentiation states are underscored by distinct chromatin looping architectures•Chromatin loops connect CD8+ T cell subset-specific enhancers, transcription factors and genes•Effector and memory CTLs have similar genome architectures, explaining rapid memory recall•BACH2, and to a lesser extent, SATB1, enforce a naive CD8+ T cell loop architecture
Russ et al. use Hi-C to map chromatin architecture dynamics during virus-specific CD8+ T cell differentiation. They demonstrate that key transcription factors preserve naivety by enforcing a naive chromatin state, and that effector and memory states are largely similar, providing a molecular explanation for rapid memory T cell function.
Non-edible oil-seed cakes of neem, madhuca and simarouba were subjected to natural decomposition by simple pit method in CR design during 2020–21 at UAS, GKVK, Bangalore. The physicochemical ...parameters temperature, pH, EC, mineral nutrients, lignin contents and phytotoxicity of oil-seed cakes during decomposition were determined at 30 days intervals for 90 days. Simultaneously, samples were also studied for the C-mineralization pattern by measuring CO2-C evolution during 60 days of the aerobic incubation experiment. The first-order kinetic model was used to describe the C-mineralization and calculate potentially mineralizable C. The decomposition of oil-seed cakes led to an increase in mineral nutrients and a decrease in lignin content and toxicity. After 60 days of the addition of soil with oil-seed cakes at different stages of compost, the cumulative C-mineralization occurred in the order neem<madhuca<simarouba. The kinetic model suggested the presence of potentially mineralizable C (C0) in the undecomposed simarouba oil-seed cake than in the neem and madhuca. This C0 decreased at 90 days of composting in all oil-seed cakes. The NMC was high in undecomposed oil-seed cakes in the order S-0>M-0>N-0. The CMC value of mature compost (90 days) was lower in neem and simarouba (6%) than in madhuca oil-seed cakes (22%). The low C-mineralization potential of raw and composted neem oil-seed cake suggested its superiority in the improvement of SOC. However, complete composting of oil-seed cakes of madhuca and simarouba was necessary for C-sequestration.
Background: Hemodialysis improves insulin sensitivity. Currently, there is no recommendation for the adjustment of insulin dose on dialysis day and nondialysis day in diabetic patients. This study ...was undertaken to determine the variations in insulin requirement based on blood glucose levels on dialysis days and nondialysis days in type 2 diabetic patients with chronic kidney disease on maintenance hemodialysis. Methodology: Twenty-eight diabetic patients on hemodialysis were recruited into the study after obtaining written informed consent and approval from Azeezia Ethics Committee. Capillary blood glucose levels, just before dialysis and 2 h after dialysis, were checked and compared with fasting and postprandial glucose levels on-off dialysis days. Results: Mean age of the patients was 59.5 (±2.3) years. The average duration of dialysis was 20.2 months. There was significant (35.8%) decrease in blood glucose levels 2 h after dialysis in comparison to predialysis levels (from mean level of 258-165 mg/dl). The decrease in the blood glucose levels from predialysis level to 2 h postdialysis level was statistically significant (P < 0.001). Both sets of data showed "strong" positive correlation with r = 0.657 and 0.849. The blood glucose levels on the day of dialysis were significantly lower than the off-day values. Conclusions: Diabetic patients with end-stage renal disease on hemodialysis have lower capillary blood glucose levels postdialysis. This has to be addressed clinically to prevent hypoglycemic episodes by reducing exogenous insulin administration on the day of dialysis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We demonstrate a unique mechanochemical effect - change in surface plastic flow by action of chemical media such as inks and glues - in large-strain deformation of metals. Unlike other well-known ...phenomena such as stress corrosion cracking and liquid metal embrittlement, the effect is not catastrophic and is largely material independent. High-speed in situ imaging shows that the media influence the flow by effecting a local ductile-to-brittle transition - from unsteady, large-amplitude, plastic folding, to repeated fracture and segmentation - with large decrease in deformation forces. The benign nature of the media offers opportunities for enhancing performance of metal cutting and deformation processes.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Background Peritoneal dialysis is used for renal replacement therapy in over 25,000 patients in the United States. Some authors have recommended laparoscopic guidance for peritoneal dialysis ...catheter (PDC) placement, although consensus statements have not favored a specific technique. This study reviews outcomes in patients in whom placement was performed by the traditional “blind” technique (B-PDC) versus the laparoscopic technique (L-PDC). Methods Records were retrospectively reviewed of 25 consecutive PDC patients in each of 3 university-affiliated tertiary medical center hospitals. Data for PDCs placed by B-PDC (n = 30) or L-PDC (n = 45) technique were reviewed and the outcomes compared. Results L-PDCs offered 97.8% immediate functional success as opposed to 80% with B-PDC placement ( P = .014). In addition, laparoscopic placement of peritoneal dialysis catheters had a lower incidence of PDC revision or replacement ( P = .035). Conclusion L-PDCs were found to have a higher immediate functional success rate than B-PDCs and a lower incidence of catheter revision or replacement.
Centella asiatica is a reputed medicinal plant used in the treatment of various skin diseases in the Indian system of medicine. The objective of the study presented in this article was to evaluate ...the wound-healing potential of the ethanolic extract of the plant in both normal and dexamethasone-suppressed wound healing. The study was done on Wistar albino rats using incision, excision, and dead space wounds models. The extract of C asiatica significantly increased the wound breaking strength in incision wound model compared to controls (P < .001). The extract-treated wounds were found to epithelize faster, and the rate of wound contraction was significantly increased as compared to control wounds (P < .001). Wet and dry granulation tissue weights, granulation tissue breaking strength, and hydroxyproline content in a dead space wound model also increased at statistically significant levels as shown. The extract of the leaves had the effect of attenuating the known effects of dexamethasone healing in all wound models (P < .001, P < .05). The results indicated that the leaf extract promotes wound healing significantly and is able to overcome the wound-healing suppressing action of dexamethasone in a rat model. These observations were supported by histology findings.
Abstract
The resolution of Shigella flexneri infection–associated hyperinflammation is crucial for host survival. Using in vitro and in vivo models of shigellosis, we found that S. flexneri induces ...the expression of indoleamine 2,3-dioxygenase 1 (IDO1) through the nucleotide oligomerization domain 2 (NOD2) and epidermal growth factor receptor (EGFR) signaling pathway. Congruently, abrogation of NOD2 or EGFR compromises the ability of S. flexneri to induce IDO1 expression. We observed that the loss of IDO1 function in vivo exacerbates shigellosis by skewing the inflammatory cytokine response, disrupting colon epithelial barrier integrity and consequently limiting the host life-span. Interestingly, administration of recombinant EGF rescued mice from IDO1 inhibition–driven aggravated shigellosis by restoring the cytokine balance and subsequently restricting bacterial growth. This is the first study that underscores the direct implication of the NOD2-EGFR axis in IDO1 production and its crucial homeostatic contributions during shigellosis. Together, these findings reveal EGF as a potential therapeutic intervention for infectious diseases.
Enteric infections are associated with intestinal dysregulation and inflammation. Epidermal growth factor receptor–driven signaling involving indoleamine 2,3-dioxygenase maintains intestinal integrity by imparting inflammatory equipoise upon encounter with agents of enterocolitis, such as Shigella flexneri.
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