Mechanism of food restriction: protection of cellular homeostasis

The major difficulty in defining the mechanisms for the action of food restriction relates to its diversity and lack of specificity. In searching for the common factor(s) and commonality involved in such diversified effects, a cellular homeostasis mechanism is proposed. A study initiated in our laboratory strongly indicates that the cellular homeostatic mechanism is seriously compromised by oxidative damage of free radical reaction with aging. Data on mitochondrial hydroperoxide, microsomal cytochrome P-450 breakdown, and reduction of cytosolic antioxidant capacity support the notion. Remarkably, food restriction attenuates all of these age-related changes. It is concluded therefore that food restriction preserves the homeostatic regulatory processes by maintaining the integrity of (i) membrane structure and function, (ii) proper redox state of cellular components, and (iii) detoxification process of xenobiotics.     

Comparative effects of trichothecene mycotoxins on bovine platelet function: Acetyl T-2 toxin,a more potent inhibitor than T-2 toxin

The effects of the trichothecene mycotoxins (acetyl T-2 toxin, T-2 toxin, HT-2 toxin, palmityl T-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON), and T-2 tetraol) on bovine platelet function were examined in homologous plasma stimulated with platelet activating factor (PAF). The mycotoxins inhibited platelet function with the following order of potency: acetyl T-2 toxin > palmityl T-2 toxin = DAS > HT-2 toxin = T-2 toxin. While T-2 tetraol was completely ineffective as an inhibitor, DON exhibited minimal inhibitory activity at concentrations above 10×10^?4M. The stability of the platelet aggregates formed was significantly reduced in all mycotoxin treated platelets compared to that of the untreated PAF controls. It is suggested that the increased sensitivity of PAF stimulated bovine platelets to the more lipophilic mycotoxins may be related to their more efficient partitioning into the platelet membrane compared to the more hydrophilic compounds.     

An extensive review on antifungal approaches in the treatment of mucormycosis

During the period of COVID-19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and rapidly progressing fungal infection associated with high mortality and morbidity in India as well as globally. The causative agents for this infection are collectively called mucoromycetes which are the members of the order Mucorales. The diagnosis of the infection needs to be performed as soon as the occurrence of clinical symptoms which differs with types of Mucorales infection. Imaging techniques magnetic resonance imaging or computed tomography scan, culture testing, and microscopy are the approaches for the diagnosis. After the diagnosis of the infection is confirmed, rapid action is needed for the treatment in the form of antifungal therapy or surgery depending upon the severity of the infection. Delaying in treatment declines the chances of survival. In antifungal therapy, there are two approaches first-line therapy (monotherapy) and combination therapy. Amphotericin B ( 1 ) and isavuconazole ( 2 ) are the drugs of choice for first-line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole ( 3 ) and deferasirox ( 4 ) is another approach for patients who are not responsible for any other therapy. Adjunctive therapy is also used in the treatment of mucormycosis along with first-line therapy, which involves hyperbaric oxygen and cytokine therapy. There are some drugs like VT-1161 ( 5 ) and APX001A ( 6 ), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis.     

Is the Tonal Quality of Birdsong Learned? Evidence from Song Sparrows

Song sparrow (Melospiza melodia) songs are composed largely of pure-tonal sounds. This paper investigates the role that learning plays in the development of the tonal structure of song sparrow songs, as well as the role that tonal quality plays in determining the suitability of songs as models for learning. 20 birds were trained with both normal pure-tonal songs and modified songs that included harmonic overtones. The harmonic-modified songs were obtained from birds singing in a helium atmosphere, the result of which is to perturb vocal tract resonances and thus alter a song's tonal quality. Subjects learned equally well from normal and harmonic models. Birds that learned material from harmonic models reproduced some of this material with harmonic overtones, but the majority of notes learned from harmonic models were subsequently reproduced as pure-tonal copies. Thus, the tonal structure of songs does not influence young song sparrows in their selection of song models, but there is a strong tendency to reproduce songs in a pure-tonal fashion, even if learned from harmonic models.     

Arginine Vasotocin Injection Increases Probability of Calling in Cricket Frogs, but Causes Call Changes Characteristic of Less Aggressive Males

Male cricket frogs,Acris crepitanscommunicate to males and females using advertisement calls, which are arranged into call groups. Calls at the middle and end, but not beginning of the call group, are modified in response to male–male aggressive interactions. We found in this field study of male cricket frogs in natural breeding choruses that the peptide hormone arginine vasotocin (AVT) not only increased the probability that males called after injections, but also caused modifications in middle and end calls to produce calls characteristic of less aggressive males. Moreover, AVT-injected males showed significantly greater increases in call dominant frequency than saline-injected males, again, a characteristic of less aggressive males. Cricket frog calls are used to both repel males and attract females, thus call changes may relate to male–male and/or male–female interactions. Saline-injected males also demonstrated significant changes in several call traits, including changes that occurred in the beginning and middle calls of the call groups, but not the end calls. AVT appeared to block some call changes produced through handling. These data suggest that AVT can influence acoustic communication in frogs in several ways, including effects on call characteristics and dominant frequency, as well as potentially blocking some handling effects.     

Monoclonal antibodies to rabbit liver cytochrome P-448

Cytochrome P-448 (mol wt 55,000 Daltons) from rabbit liver was purified to a specific content of 16.6 nmol/mg. Mice were immunised with this preparation, their spleens removed and dissociated lymphocytes hybridised with myeloma cells. Four monoclonal antibodies against cytochrome P-448 were raised and partially characterised. All four antibodies interacted with cytochrome P-448 in intact microsomal fractions and selectively immunoadsorbed cytochrome P-448 from solubilised microsomal preparations. One of the antibodies inhibited benzo[a] pyrene hydroxylase activity in a reconstituted system, one had no effect on activity and two increased activity. The possible applications of such antibodies are discussed.     

Long-term storage of learned birdsongs prior to production

Sixteen male swamp sparrows, Melospiza georgiana, were reared by hand in the laboratory and exposed in infancy to tape-recorded songs. Training ended around 2 months of age. Samples of singing were tape recorded sporadically from the age of 50 to 90 days and on a weekly basis from about 95 to 400 days. Analysis revealed that explicit rehearsal of learned songs did not begin, on the average, until 240 days after the last exposure to training songs. Swamp sparrows can commit song syllables to memory and produce imitations of them 8 months later with no rehearsal in the interim.     

Saikosaponin-d,a novel SERCA inhibitor,induces autophagic cell death in apoptosis-defective cells

Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase pump, leading to autophagy induction through the activation of the Ca²⁺/calmodulin-dependent kinase kinase–AMP-activated protein kinase–mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells.