Antigen binding to receptors on immunocompetent cells. II. Thermodynamic and biological implications of the receptor cross-linking requirement for B-cell activation.

If one assumes that receptor cross-linking is a necessary, but not sufficient condition for cellular activation, a number of predictions can be made bearing on the physical chemical properties of the cells selected. In this paper we show that the following response characteristics can be consequences of a cross-linking requirement. (1) Small sparsely haptenated antigens such as DNP₁₀BSA are expected to elicit a response that matures, and such maturation can occur even with antigenic determinant density in excess over the concentration of cellular receptors. (2) There is an optimal concentration for activation of cells with a given affinity, and therefore an optimally immunogenic dose. (3) The optimal dose is relatively insensitive to antigen valence. (4) Increasing valence increases the breadth of the affinity distribution. (5) For supra optimal doses of antigen, unresponsiveness will be preferentially induced in high affinity cells. (6) Small densely haptenated antigens (e.g. DNP₄₀BSA) are not expected to elicit responses that mature as quickly as those that are lightly coupled. (7) Large polymeric antigens are not expected to induce responses that mature. (8) Antigens with low determinant density may induce tolerance in vivo but not in vitro. The predictions are briefly discussed in the context of relevant experimental data.     

Effect of post-synthetic modifications of proteins on the binding of estrogen-receptor complex to uterine nuclei of aging rats

The binding of estrogen-receptor (ER) complex to nuclei following post-synthetic modifications of proteins was examined in the uteri of young (18 weeks) and old (96 weeks) rats. Acetylation decreases the binding of ER complex to nuclei but methylation shows no effect on the extent of binding in both ages. On the other hand, phosphorylation enhances the binding of ER complex by two-fold in nuclei from young rats but reduces this to half in nuclei from old rats. The pattern of binding in salt-resistant nuclear fractions is similar to that in total nuclei except in methylation where old rats show about 20% higher binding as compared to the respective control. These findings suggest that post-synthetic modifications of proteins modulate the binding of ER complex to uterine nuclei in an age-specific manner.     

Studies in the life cycle of Allomyces javanicus Kniep

Summary The life cycle of Allomyces javanicus was studied with the hanging drop method under laboratory conditions. The isolate has a life cyrle similar to that already described in A. javanicus and A. arbuscula. Planonts from resistant sporangia do not germinate directly to produce gametophytic plants, but on the contrary, the latter germinate to produce plants like their immediate parents. Female and male gametes growing in the gametangia of relatively young sexual mycelia develop into asexual mycelia after conjugation, but some of the female gametes after germination develop into asexual mycelia without conjugation.     

The influence of hyperglycemia on the safety of ultrasound in retinal pigment epithelial cells

Ultrasound (US) assisted drug delivery is receiving interest in treating posterior eye diseases, such as diabetic retinopathy due to its ability to maximize drug penetration into difficult to reach tissues. Despite its promise, the technique has only been investigated using healthy cell and tissue models, with no evidence to date about its safety in active disease. As a result, the aim of this study was to evaluate the safety of US administration in vitro in retinal pigment epithelial cells under normal and high glucose conditions. US protocols within the presently accepted safety threshold were applied and their influence on cell membrane and tight junction integrity as well as intracellular inflammation was evaluated using lactate dehydrogenase (LDH), zona occludens-1 (ZO-1), fluorescein isothiocyanate (FITC)-dextran dye leak and nuclear factor-kappaB (NF-κB) assays, respectively. Under high glucose conditions, US application increased LDH release and resulted in loss of ZO-1 labeling at 2 h; however, normal levels were restored within 24 h. US within its safety parameters did not induce any FITC-dextran dye leak or NF-κB nuclear translocation in normal or high glucose conditions. In conclusion, our results suggest that while high glucose conditions increase cell susceptibility to US-mediated stress, basal conditions can be restored within 24 h without long-lasting cell damage.     

Glyphosate inhibits melanization and increases susceptibility to infection in insects

Melanin, a black-brown pigment found throughout all kingdoms of life, has diverse biological functions including UV protection, thermoregulation, oxidant scavenging, arthropod immunity, and microbial virulence. Given melanin’s broad roles in the biosphere, particularly in insect immune defenses, it is important to understand how exposure to ubiquitous environmental contaminants affects melanization. Glyphosate—the most widely used herbicide globally—inhibits melanin production, which could have wide-ranging implications in the health of many organisms, including insects. Here, we demonstrate that glyphosate has deleterious effects on insect health in 2 evolutionary distant species, Galleria mellonella (Lepidoptera: Pyralidae) and Anopheles gambiae (Diptera: Culicidae), suggesting a broad effect in insects. Glyphosate reduced survival of G. mellonella caterpillars following infection with the fungus Cryptococcus neoformans and decreased the size of melanized nodules formed in hemolymph, which normally help eliminate infection. Glyphosate also increased the burden of the malaria-causing parasite Plasmodium falciparum in A. gambiae mosquitoes, altered uninfected mosquito survival, and perturbed the microbial composition of adult mosquito midguts. Our results show that glyphosate’s mechanism of melanin inhibition involves antioxidant synergy and disruption of the reaction oxidation–reduction balance. Overall, these findings suggest that glyphosate’s environmental accumulation could render insects more susceptible to microbial pathogens due to melanin inhibition, immune impairment, and perturbations in microbiota composition, potentially contributing to declines in insect populations.

Glyphosate, the most commonly used herbicide in the world, inhibits the production of melanin. Melanin is an important pigment and a key component of the insect immune system; this study shows that glyphosate weakens insects’ melanin-based immune system and makes them more vulnerable to infections, including with the human malaria parasite Plasmodium falciparum.     

Kynurenine Metabolism and Alzheimer’s Disease: The Potential Targets and Approaches

l-tryptophan, an essential amino acid, regulates protein homeostasis and plays a role in neurotransmitter-mediated physiological events. It also influences age-associated neurological alterations and neurodegenerative changes. The metabolism of tryptophan is carried majorly through the kynurenine route, leading to the production of several pharmacologically active enzymes, substrates, and metabolites. These metabolites and enzymes influence a variety of physiological and pathological outcomes of the majority of systems, including endocrine, haemopoietic, gastrointestinal, immunomodulatory, inflammatory, bioenergetic metabolism, and neuronal functions. An extensive literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out to understand the nature of the extensive work done on the kynurenine metabolites that influence cellular redox potential, immunoregulatory mechanisms, inflammatory pathways, cell survival channels, and cellular communication in close association with several neurodegenerative changes. The imbalanced state of kynurenine pathways has found a close association to several pathological disorders, including HIV infections, cancer, autoimmune disorders, neurodegenerative and neurological disorders including Parkinson’s disease, epilepsy and has found special attention in Alzheimer's disease (AD). Kynurenine pathway (KP) is intricately linked to AD pathogenesis owing to the influence of kynurenine metabolites on excitotoxic neurotransmission, oxidative stress, uptake of neurotransmitters, and modulation of neuroinflammation, amyloid aggregation, microtubule disruption, and their ability to induce a state of dysbiosis. Pharmacological modulation of KP pathways has shown encouraging results, indicating that it may be a viable and explorable target for the therapy of AD.

     

Growth and metabolic responses of contrasting chickpea (<Emphasis Type="Italic">Cicer arietinum</Emphasis> L.) genotypes to chilling stress at reproductive phase

Chilling stress (<10°C) at reproductive phase of chickpea results in abortion of flowers and pods leading to poor yield. The metabolic causes associated with cold sensitivity of chickpea are not well understood. Hence, in the present study, we evaluated four chickpea genotypes (ICC 16348, ICC 16349, PBG1 and GPF2) having contrasting cold sensitivity for their reproductive growth and metabolism subjected to cold stress (average day temperature: 17.6°C; average night temperature: 4.9°C). Genotypes ICC 16348 and ICC 16349 showed flowering and set pods, while PBG1 and GPF2 failed to do so during the stress conditions indicating the former to be cold tolerant. The stress injury in the leaves such as increase in electrolyte leakage, decrease in chlorophyll content and relative leaf water content was significantly less in ICC 16348 and ICC 16349 genotypes. The analysis of carbohydrates indicated total sugars and starch to be present in greater content in ICC 16348 and ICC 16349 relative to PBG1 and GPF2 genotypes. The enzymes related to carbohydrate metabolism such as β-amylase, invertase and sucrose synthase showed significantly higher activity in the leaves of ICC 16348 and ICC 16349 compared to the other two genotypes. PBG1 and GPF2 genotypes experienced greater oxidative stress measured as malondialdehyde and hydrogen peroxide. ICCV 16348 and ICC 16349 possessed significantly higher levels of enzymatic (superoxide dismutase, catalase, ascorbate peroxidase) and non-enzymatic antioxidants (proline and ascorbic acid) relative to PBG1 and GPF2. Particularly, proline and ascorbic acid were markedly higher in cold-tolerant genotypes compared to the sensitive ones suggesting their deciding role in governing the cold tolerance.     

An efficient method for explant sterilization for reduced contamination

An improved method for sterilization of explants was tested and found to be suitable for plants with elongated internodes, such as bamboos. Final cutting of the explants into single nodal segments for inoculation was done only after surface sterilization of multi-nodal explants in a stoppered glass measuring cylinder. This minimized penetration of the contaminants and the sterilizing agents into the exposed intercellular spaces and vascular cavities at the cut ends, thereby minimizing their harmful effects. The method was experimented upon three different plants, viz., bamboo, tea and rose. Through this method the number of cultures getting contaminated was substantially reduced as compared to the conventional means where single nodal explants were used, employing identical treatments. Moreover, in this method, the number of cultures showing bud-break also showed a marked increase thereby resulting in a tremendous increase in the percentage of successfully established proliferating cultures.