Exploring the viability of Zeatin as a prospective therapeutic candidate for investigating the complex interplay between severe acute respiratory syndrome coronavirus (SARS-CoV) and Alzheimer's disease.

The present research aims to explore the intricate link between SARS-CoV infection and susceptibility to Alzheimer's disease, focusing on the role of APOE4, a genetic factor associated with both conditions. Our research aims to uncover shared molecular pathways, considering APOE4's impact on lipid metabolism, immune responses, and neuroinflammation relevant to COVID-19 and AD. The Chyawanprash phytocompounds were subjected to in-silico ADMET profiling and Zeatin a neuroprotective cytokinin emerged as a promising regulator of the ACE2-SPIKE complex as it exhibits favourable pharmacological attributes, presenting as a non-substrate for Permeability glycoprotein, low Protein Binding Percentage, and distinctive toxicity endpoints. Therapeutic candidate. Zeatin's robust binding disrupts the intricate APOE4-ACE2-SPIKE interplay (AAS), offering a potential therapeutic avenue that is further corroborated by Molecular dynamic simulation as the system remained stable without any major fluctuation throughout the 100ns simulation. The AAS binding free energy, determined as -124.849 +/- 15.513 KJ/mol using MMPBSA assay, reveals significant contributions to complex stability from amino acids including, GLN41: 1.211 kcal/mol, GLU340: 1.188 kcal/mol, ALA344: 1.198 kcal/mol, while ARG38: 2.011 kcal/mol establishes pivotal strong bonds integral to the interaction between AAS and Zeatin. Rigorous cytotoxicity assessments reveal Zeatin's safety profile, highlighting its inhibitory effect on LN18 cell viability that sharply decreases to 32.47% at 200 µg/ml, underscoring its modulatory impact on cellular metabolism. These findings enhance our understanding of the convergent mechanisms linking SARS-CoV and AD, providing valuable insights for potential therapeutic interventions. Further research is warranted to elucidate the specific pathways and molecular mechanisms through which zeatin exerts its protective effects.

Relative importance of VECTRI model parameters in the malaria disease transmission and prevalence.

In this study, a sensitivity analysis on a VECTRI dynamical model of malaria transmission is investigated to determine the relative importance of model parameters to disease transmission and prevalence. Apart from being most climatic prone, Odisha is a highly endemic state for malaria in India. The lack in sufficient modeling studies severely impacts the malarial process studies which further hinder the possibility of malaria early warning systems and preventive measures to be undertaken beforehand. Therefore, modeling studies and investigating the relationship between malaria transmission process studies and associated climatic factors are the need of the hour. Environmental conditions have pronounced effects on the malaria transmission dynamics and abundance of the poikilothermic vectors, but the exact relationship of sensitivity for these parameters is not well established. Sensitivity analysis is a useful tool for ascertaining model responses to different input variables. Therefore, in order to perform the requisite study, a dynamical model, VECTRI, is utilized. The study period ranges from 2000 to 2013, where several sensitivity tests are performed using different model parameters such as infiltration and evaporation rate loss of ponds, degree-days for parasite development, threshold temperature for parasite development, threshold temperature for egg development in the vector, and maximum and minimum temperature for larvae survival. The experiments suggest that the lower value of minimum temperature for larvae survival (rlarv_tmin), i.e., 16 °C, provides higher vector density and entomological inoculation rate (EIR) values. EIR reaches its maximum, when the threshold temperature for parasite development (rtsporo) is 22 °C and degree-days for parasite development (dsporo) is 8 degree-days. No change is observed in the vector density; even when rtsporo is 30 °C, values of EIR are close to 0. A successive increment of infiltration and evaporation rate loss of ponds (rwaterfrac evap126) values from 130 to 200 mm/day result in approximately 5% consistent decline in vector density and EIR. The study concludes that the most sensitive parameters are dsporo, rlarv_tmin, and rwaterfrac evap126. The VECTRI model is rather insensitive to maximum temperature for larvae survival (rlarv_tmin) for vector density and EIR variables. Further certain modifications and improvements are required in VECTRI to predict out variables like vector density and EIR more accurately in highly endemic region.

Rhizobacterial mediated interactions in Curcuma longa for plant growth and enhanced crop productivity: a systematic review.

Turmeric (Curcuma longa L.), a significant commercial crop of the Indian subcontinent is widely used as a condiment, natural dye, and as a cure for different ailments. Various bioactive compounds such as turmerones and curcuminoids have been isolated from C. longa that have shown remarkable medicinal activity against various ailments. However, reduced soil fertility, climatic variations, rapid urbanization, and enhanced food demand, pose a multifaceted challenge to the current agricultural practices of C. longa. Plant growth-promoting microbes play a vital role in plant growth and development by regulating primary and secondary metabolite production. Rhizospheric associations are complex species-specific interconnections of different microbiota with a plant that sustain soil health and promote plant growth through nutrient acquisition, nitrogen fixation, phosphate availability, phytohormone production, and antimicrobial activities. An elaborative study of microbiota associated with the roots of C. longa is essential for rhizospheric engineering as there is a huge potential to develop novel products based on microbial consortium formulations and elicitors to improve plant health, stress tolerance, and the production of secondary metabolites such as curcumin. Primarily, the purpose of this review is to implicate the rhizospheric microbial flora as probiotics influencing overall C. longa health, development, and survival for an increase in biomass, enhanced yield of secondary metabolites, and sustainable crop production.

In-silico modeling of the interplay between APOE4, NLRP3, and ACE2-SPIKE complex in neurodegeneration between Alzheimer and SARS-CoV: implications for understanding pathogenesis and developing therapeutic strategies.

The multifaceted interplay between neurodegenerative pathologies, including Alzheimer's disease (AD), and the highly virulent severe acute respiratory syndrome coronavirus (SARS-CoV), is implicated in various conditions. AD and SARS-CoV pathogenesis involve the APOE4 allele, NLRP3 inflammasome, and ACE2-SPIKE complex. APOE4, a genetic polymorphism of the APOE gene, is associated with an increased susceptibility to AD. NLRP3, an inflammatory protein of the innate immune system, plays a pivotal role in immune response cascades. In SARS-CoV, the ACE2 receptor serves as the principal portal for cellular entry, while APOE4 intricately interacts with the ACE2-spike protein complex, enhancing viral internalization process. The interaction of NLRP3 with the ACE2-spike protein complex leads to increased inflammatory signaling. The convergence of APOE4/NLRP3 and ACE2-spike protein complex interactions suggests a possible link between SARS and AD. Therefore, the current research centralizes the association between by utilizing SARS-CoV datasets to explore possible mechanisms that account for the pathogenesis of SARS-CoV and AD. The work is further extended to unveil the molecular interactions of APOE4 and NLRP3 with the ACE2-Spike protein complex at the molecular level by employing molecular dynamics simulation techniques. The therapeutic efficacy of Chyawanprash nutraceuticals is evaluated as their inhibitory potential towards APOE4-ACE2-Spike protein and NLRP3-ACE2-Spike protein complexes. Notably, our simulations unequivocally demonstrate the robust and enduring binding capability of the compound Phyllantidine with the target complexes throughout the simulation period. The findings of the studies further corroborate the primary hypothesis of APOE4 and NLRP3 as driver factors in the pathogenesis of both SARS-CoV and AD. Therefore, this research establishes a paradigm for comprehending the complex interaction between AD and SARS-CoV and lays the groundwork for further study in this domain.Communicated by Ramaswamy H. Sarma.

Revisiting the Nutritional, Chemical and Biological Potential of Cajanus cajan (L.) Millsp.

The genus Cajanus (Family: Fabaceae) consists of approximately 37 species, and Cajanus cajan (C. cajan) is a significant member of the genus. It is a commercial legume crop widely grown in sub-tropical and semi-arid tropical areas of the world. C. cajan is well known for its folk medicinal uses to treat various disorders, such as toothache, dizziness, diabetes, stomachache, female ailments and chronic infections. These properties have been linked to the presence of several value-added nutritional and bioactive components. Different solvent extracts from C.cajan (leaves, root, stem and seeds) have been evaluated for their phytochemical and biological activities, namely antioxidant, antimicrobial, antidiabetic, neuroprotective, and anti-inflammatory effects. Taken together, and considering the prominent nutraceutical and therapeutic properties of C. cajan, this review article focuses on the important details including ethnomedicinal uses, chemical composition, biological applications and some other medicinal aspects related to C.cajan nutraceutical and pharmacological applications.

Potential future malaria transmission in Odisha due to climate change.

Future projections of malaria transmission is made for Odisha, a highly endemic region of India, through numerical simulations using the VECTRI dynamical model. The model is forced with bias-corrected temperature and rainfall from a global climate model (CCSM4) for the baseline period 1975-2005 and for the projection periods 2020s, 2050s, and 2080s under RCP8.5 emission scenario. The temperature, rainfall, mosquito density and entomological inoculation rate (EIR), generated from the VECTRI model are evaluated with the observation and analyzed further to estimate the future malaria transmission over Odisha on a spatio-temporal scale owing to climate change. Our results reveal that the malaria transmission in Odisha as a whole during summer and winter monsoon seasons may decrease in future due to the climate change except in few districts with the high elevations and dense forest regions such as Kandhamal, Koraput, Raygada and Mayurbhanj districts where an increase in malaria transmission is found. Compared to the baseline period, mosquito density shows decrease in most districts of the south, southwest, central, north and northwest regions of Odisha in 2030s, 2050s and 2080s. An overall decrease in malaria transmission of 20-40% (reduction in EIR) is seen during the monsoon season (June-Sept) over Odisha with the increased surface temperature of 3.5-4 °C and with the increased rainfall of 20-35% by the end of the century with respect to the baseline period. Furthermore, malaria transmission is likely to reduce in future over most of the Odisha regions with the increase in future warm and cold nights temperatures.

Diplazium esculentum (Retz.) Sw.: Ethnomedicinal, Phytochemical, and Pharmacological Overview of the Himalayan Ferns.

The genus Diplazium (family: Athyriaceae) comprises approximately 350 species of pteridophytes. Diplazium esculentum (Retz.) Sw. is an important member of this genus and commonly known as a wild vegetable in the Himalayan and sub-Himalayan communities. According to the literature analysis, D. esculentum was traditionally used for the prevention or treatment of several diseases such as diabetes, smallpox, asthma, diarrhea, rheumatism, dysentery, headache, fever, wounds, pain, measles, hypertension, constipation, oligospermia, bone fracture, and glandular swellings. Various extracts of D. esculentum were evaluated to elucidate their phytochemical and pharmacological activities. A wide array of pharmacological properties such as antioxidant, antimicrobial, antidiabetic, immunomodulatory, CNS stimulant, and antianaphylactic activities have been recognized in different parts of D. esculentum. The review covers a systematic examination of pharmacognosy, phytochemistry, and pharmacological applications of D. esculentum, but scientifically, it is not fully assessed regarding complete therapeutic effects, toxicity, and safety in the human body. The published literature on D. esculentum and its therapeutic properties were collected from different search engines including Wiley online, PubMed, Springer Link, Scopus, Science Direct, Web of Science, Google Scholar, and ACS publications by using specific terms such as "Diplazium esculentum, bioactive compounds, biological activities and health benefits" from 1984 to 2021 (March). Therefore, further studies are required to identify the detailed action mechanism of D. esculentum in vitro/in vivo, and also, more studies should focus on conservation, cultivation, and sustainable utilization of the species.

Rhythmic breathing: immunological, biochemical, and physiological effects on health.

Yoga and breathing techniques have become increasingly popular in recent decades. Sudarshan Kriya (SK) is a type of rhythmic and controlled breathing that involves cyclic breathing in which long breaths are followed by medium and short breaths. Scientific research has been conducted to study the effects of SK on different physiological parameters. Various studies have shown that the technique is simple and cost effective and can be used as a complementary therapy, together with ongoing conventional treatments, to help people suffering from extreme levels of stress, anxiety, and other physical problems. Studies have demonstrated that SK can play an important role in promoting a healthy lifestyle by improving immunity, antioxidant status, hormonal status, and brain functioning. Through available scientific evidence and research, the current article aims to review the complementary role of rhythmic breathing (ie, SK) as a practical and effective tool to alleviate stress, improve health, and increase wellness.

Whole-genome sequence of a classical Swine Fever virus isolated from the uttarakhand state of India.

We report the first complete genome sequence of a classical swine fever (CSF) virus of subgenotype 2.2. The virus (CSFV/IND/UK/LAL-290) was isolated from the Uttarakhand state of India from a backyard pig suspected of having CSF. This genome sequence will give useful insight for future molecular epidemiological studies and the development of an effective vaccine in India.

Small G Proteins Dexras1 and RHES and Their Role in Pathophysiological Processes.

Dexras1 and RHES, monomeric G proteins, are members of small GTPase family that are involved in modulation of pathophysiological processes. Dexras1 and RHES levels are modulated by hormones and Dexras1 expression undergoes circadian fluctuations. Both these GTPases are capable of modulating calcium ion channels which in turn can potentially modulate neurosecretion/hormonal release. These two GTPases have been reported to prevent the aberrant cell growth and induce apoptosis in cell lines. Present review focuses on role of these two monomeric GTPases and summarizes their role in pathophysiological processes.

Binding pattern of 125iodine thyroxine and tri-iodothyronine in skin and liver tissues of spotted munia, Lonchura punctulata: co-relation to seasonal cycles of breeding and molting.

Prevalent notion about thyroid hormones is that thyroxine (T4) is a mere precursor and physiological effects of thyroid hormones are elicited by tri-iodothyronine (T3) after mono-deiodination of T4. Earlier studies on feather regeneration and molt done on spotted munia L. punctulata suggest that T4 (mono-deiodination suppressed by iopanoic acid and thyroidectomized birds) is more effective than T3 in inducing feather regeneration. The binding pattern of 125I labeled T4 and T3 has been investigated in the nuclei prepared from skin and liver tissues (samples obtained during different months) of spotted munia using scatchard plot analysis. The results show that binding capacity (B(max)--pmole/80 microgm DNA) of 125I-T3 to nuclei of skin was significantly higher in November as compared to April and June, whereas the binding affinity (Kd-10(-9)M(-1)) was significantly lower in November as compared to April and June. During November, B(max) for binding of T3 and T4 did not vary in liver and skin nuclei but Kd varied significantly. Binding capacity of 125I- T3 to skin and liver did not vary but binding affinity of 125I- T4 to skin was approximately 7 times higher than that of liver. The results suggest that T4 does show a variation in binding pattern that co-relates to the molting pattern of spotted munia. These variations might play important role in different physiological phenomenon in this tropical bird. The experiments do point towards the possibility of independent role of T4 as a hormone, however, further experiments need to be done to ascertain the role of T4 in this model and work out the exact molecular mechanism of action.

The monomeric G proteins AGS1 and Rhes selectively influence Galphai-dependent signaling to modulate N-type (CaV2.2) calcium channels.

Activator of G protein Signaling 1 (AGS1) and Ras homologue enriched in striatum (Rhes) define a new group of Ras-like monomeric G proteins whose signaling properties and physiological roles are just beginning to be understood. Previous results suggest that AGS1 and Rhes exhibit distinct preferences for heterotrimeric G proteins, with AGS1 selectively influencing Galphai and Rhes selectively influencing Galphas. Here, we demonstrate that AGS1 and Rhes trigger nearly identical modulation of N-type Ca(2+) channels (Ca(V)2.2) by selectively altering Galphai-dependent signaling. Whole-cell currents were recorded from HEK293 cells expressing Ca(V)2.2 and Galphai- or Galphas-coupled receptors. AGS1 and Rhes reduced basal current densities and triggered tonic voltage-dependent (VD) inhibition of Ca(V)2.2. Additionally, each protein attenuated agonist-initiated channel inhibition through Galphai-coupled receptors without reducing channel inhibition through a Galphas-coupled receptor. The above effects of AGS1 and Rhes were blocked by pertussis toxin (PTX) or by expression of a Gbetagamma-sequestering peptide (masGRK3ct). Transfection with HRas, KRas2, Rap1A-G12V, Rap2B, Rheb2, or Gem failed to duplicate the effects of AGS1 and Rhes on Ca(V)2.2. Our data provide the first demonstration that AGS1 and Rhes exhibit similar if not identical signaling properties since both trigger tonic Gbetagamma signaling and both attenuate receptor-initiated signaling by the Gbetagamma subunits of PTX-sensitive G proteins. These results are consistent with the possibility that AGS1 and Rhes modulate Ca(2+) influx through Ca(V)2.2 channels under more physiological conditions and thereby influence Ca(2+)-dependent events such as neurosecretion.

Neurokinin 1 receptors trigger overlapping stimulation and inhibition of CaV2.3 (R-type) calcium channels.

Neurokinin (NK) 1 receptors and CaV2.3 calcium channels are both expressed in nociceptive neurons, and mice lacking either protein display altered responses to noxious stimuli. Here, we examined modulation of CaV2.3 through NK1 receptors expressed in human embryonic kidney 293 cells. We find that NK1 receptors generate complex modulation of CaV2.3. In particular, weak activation of these receptors evokes mainly stimulation of CaV2.3, whereas strong receptor activation elicits profound inhibition that overlaps with channel stimulation. Unlike R-type channels encoded by CaV2.3, L-type (CaV1.3), N-type (CaV2.2), and P/Q-type (CaV2.1) channels are inhibited, but not stimulated, through NK1 receptors. Pharmacological experiments show that protein kinase C (PKC) mediates stimulation of CaV2.3 through NK1 receptors. The signaling mechanisms underlying inhibition were explored by expressing proteins that buffer either Galpha(q/11) (regulator of G protein signaling protein 3T and carboxyl-terminal region of phospholipase C-beta1) or Gbeta gamma subunits (transducin and the carboxyl-terminal region of bovine G-protein-coupled receptor kinase). A fast component of inhibition was attenuated by buffering Gbeta gamma, whereas a slow component of inhibition was reduced by buffering Galpha(q/11). When both Gbeta gamma and Galpha(q/11) were simultaneously buffered in the same cells, inhibition was virtually eliminated, but receptor activation still triggered substantial stimulation of CaV2.3. We also report that NK1 receptors accelerate the inactivation kinetics of CaV2.3 currents. Altogether, our results indicate that NK1 receptors modulate CaV2.3 using three different signaling mechanisms: a fast inhibition mediated by Gbeta gamma, a slow inhibition mediated by Galpha(q/11), and a slow stimulation mediated by PKC. This new information concerning R-type calcium channels and NK1 receptors may help in understanding nociception, synaptic plasticity, and other physiological processes.

Muscarinic modulation of Cav2.3 (R-type) calcium channels is antagonized by RGS3 and RGS3T.

Ca(2+) influx through voltage-gated R-type (Ca(V)2.3) Ca(2+) channels is important for hormone and neurotransmitter secretion and other cellular events. Previous studies have shown that Ca(V)2.3 is both inhibited and stimulated through signaling mechanisms coupled to muscarinic ACh receptors. We previously demonstrated that muscarinic stimulation of Ca(V)2.3 is blocked by regulator of G protein signaling (RGS) 2. Here we investigated whether muscarinic inhibition of Ca(V)2.3 is antagonized by RGS3. RGS3 is particularly interesting because it contains a lengthy ( approximately 380 residue) amino-terminal domain of uncertain physiological function. Ca(V)2.3, M(2) muscarinic ACh receptors (M(2)R), and various deletion mutants of RGS3, including its native isoform RGS3T, were expressed in HEK293 cells, and agonist-dependent inhibition of Ca(V)2.3 was quantified using whole cell patch-clamp recordings. Full-length RGS3, RGS3T, and the core domain of RGS3 were equally effective in antagonizing inhibition of Ca(V)2.3 through M(2)R. These results identify RGS3 and RGS3T as potential physiological regulators of R-type Ca(2+) channels. Furthermore, they suggest that the signaling activity of RGS3 is unaffected by its extended amino-terminal domain. Confocal microscopy was used to examine the intracellular locations of four RGS3-enhanced green fluorescent protein fusion proteins. The RGS3 core domain was uniformly distributed throughout both cytoplasm and nucleus. By contrast, full-length RGS3, RGS3T, and the amino-terminal domain of RGS3 were restricted to the cytoplasm. These observations suggest that the amino terminus of RGS3 may serve to confine it to the cytoplasmic compartment where it can interact with cell surface receptors, heterotrimeric G proteins, and other signaling proteins.

Daily increments of light hours near vernal equinox synchronize circannual testicular cycle of tropical spotted munia.

In some long-lived organisms, particularly in tropical birds and migrants that spend part of the year close to the equator, endogenous circannual rhythms have been demonstrated in seasonal events like reproduction, molt, and migration. These, like the circadian rhythms, are expressed only in constant conditions of illumination with a periodicity deviating from 1 yr. If birds followed this periodicity, they would soon be out of phase with the annual calendar and perish and, therefore, they would need to be synchronized. However, almost nothing is known as to how synchronization is achieved in birds. Herein, with the help of a suitable model, viz., the tropical spotted munia and long-term experiments conducted in series over a 5-yr period, we provide direct evidence for the first time indicating that the segment of annual photocycle with maximal rate of increase prior to vernal equinox (approximately between mid-February and mid-March) synchronizes the circannual reproductive cycle with the monsoon period of ample food supply through a phase delay. Data also indicate, contrary to the prevalent view, that birds in the tropics can perceive minor changes in day-length, that birds respond to progressive changes in day-length as distinct from responding to fixed photoperiods of particular durations, and that birds can actually distinguish the quality of the environmental signal, viz., vernal equinox from early spring, or increasing days of spring from decreasing days of autumn. The underlying mechanisms, although yet to be identified, appear to involve a gonado-inhibitory rather than the conventional gonado-stimulatory response to increasing day-length. The photoperiodic responses of spotted munia are distinctly different from that of any "long-day" birds described thus far and do not conform to the prevalent "circadian coincidence" hypothesis of photoperiodism.

Superactivation of bound entanglement.

We show that, in a multiparty setting, two nondistillable (bound-entangled) states tensored together can make a distillable state. This is an example of true superadditivity of distillable entanglement. We also show that unlockable bound-entangled states cannot be asymptotically unentangled, providing the first proof that some states are truly bound-entangled in the sense of being both nondistillable and nonseparable asymptotically.