Force and power requirement for development of cumin harvester: a dynamic approach.

An experimental setup was developed for simulating the field conditions to determine the force and power required for cutting cumin crops in dynamic conditions. The effect of cutter bar speeds, forward speeds, and blade type on cutting force and power requirement for cutting cumin were also studied. Experiments were carried out at three levels: cutter bar speeds, forward speeds, and blade type. The results showed that all the factors significantly affected cutting force. The cutting force followed a decreasing trend with the increase in cutter bar speed. Whereas it followed an increasing trend with the increase in forward speed. The maximum cutting force for all three blades was observed at a cutter bar speed of 2.00 strokes.s-1 and forward speed of 0.46 m.s-1. The idle power and actual power required for cutting the cumin crop were also determined based on the cutting force. The results obtained were validated by the power drawn from the power source while operating the cutter bar blades. The R2 values for Blade-B1, Blade-B2, and Blade-B3 were 0.90, 0.82, and 0.88, respectively. The cutting force was primarily affected by the cutter bar speed, resulting in PCR values of 74.20%, 82.32%, and 81.75% for Blade-B1, Blade-B2, and Blade-B3, respectively, followed by the forward speed, which also had an impact on PCR values of 16.60%, 15.27%, and 18.25% for Blade-B1, Blade-B2, and Blade-B3, respectively. The cutting force for Blade-B1, Blade-B2, and Blade-B3 varied from 15.96 to 58.97 N, 21.08 to 76.64 N, and 30.22 to 85.31, respectively, for the selected range of cutter bar speed and forward speed. Blade-B1 had 18 and 30% less power consumption than Blade-B2 and Blade-B3, respectively.

Drug repurposing for personalized medicine.

Personalized medicine has emerged as a revolutionary approach to healthcare in the 21st century. By understanding a patient's unique genetic and biological characteristics, it aims to tailor treatments specifically to the individual. This approach takes into account factors such as an individual's lifestyle, genetic makeup, and environmental factors to provide targeted therapies that have the potential to be more effective and lower the risk of side reactions or ineffective treatments. It is a paradigm shift from the traditional "one size fits all" approach in medicine, where patients with similar symptoms or diagnoses receive the same standard treatments regardless of their differences. It leads to improved clinical outcomes and more efficient use of healthcare resources. Drug repurposing is a strategy that uses existing drugs for new indications and aims to take advantage of the known safety profiles, pharmacokinetics, and mechanisms of action of these drugs to accelerate the development process. Precision medicine may undergo a revolutionary change as a result, enabling the rapid development of novel treatment plans utilizing drugs that traditional methods would not otherwise link to. In this chapter, we have focused on a few strategies wherein drug repurposing has shown great success for precision medicine. The approach is particularly useful in oncology as there are many variations induced in the genetic material of cancer patients, so tailored treatment approaches go a long way. We have discussed the cases of breast cancer, glioblastoma and hepatocellular carcinoma. Other than that, we have also looked at drug repurposing approaches in anxiety disorders and COVID-19.

Exploring the potential of drug repurposing for treating depression.

Researchers are interested in drug repurposing or drug repositioning of existing pharmaceuticals because of rising costs and slower rates of new medication development. Other investigations that authorized these treatments used data from experimental research and off-label drug use. More research into the causes of depression could lead to more effective pharmaceutical repurposing efforts. In addition to the loss of neurotransmitters like serotonin and adrenaline, inflammation, inadequate blood flow, and neurotoxins are now thought to be plausible mechanisms. Because of these other mechanisms, repurposing drugs has resulted for treatment-resistant depression. This chapter focuses on therapeutic alternatives and their effectiveness in drug repositioning. Atypical antipsychotics, central nervous system stimulants, and neurotransmitter antagonists have investigated for possible repurposing. Nonetheless, extensive research is required to ensure their formulation, effectiveness, and regulatory compliance.

Drug repurposing for fungal infections.

The rise of multidrug-resistant bacteria is a well-recognized threat to world health, necessitating the implementation of effective treatments. This issue has been identified as a top priority on the global agenda by the World Health Organization. Certain strains, such as Candida glabrata, Candida krusei, Candida lusitaniae, Candida auris, select cryptococcal species, and opportunistic Aspergillus or Fusarium species, have significant intrinsic resistance to numerous antifungal medicines. This inherent resistance and subsequent suboptimal clinical outcomes underscore the critical imperative for enhanced therapeutic alternatives and management protocols. The challenge of effectively treating fungal infections, compounded by the protracted timelines involved in developing novel drugs, underscores the pressing need to explore alternative therapeutic avenues. Among these, drug repurposing emerges as a particularly promising and expeditious solution, providing cost-effective solutions and safety benefits. In the fight against life-threatening resistant fungal infections, the idea of repurposing existing medications has encouraged research into both established and new compounds as a last-resort therapy. This chapter seeks to provide a comprehensive overview of contemporary antifungal drugs, as well as their key resistance mechanisms. Additionally, it seeks to provide insight into the antimicrobial properties of non-traditional drugs, thereby offering a holistic perspective on the evolving landscape of antifungal therapeutics.

Enhancing soil quality and yield through microbial assisted in-situ residue management in rice-rice cropping system in Odisha, Eastern India.

Crop residue management has become more challenging with intensive agricultural operations. Zero tillage and crop residue returns, along with the enhancement of in-situ residue decomposition through microbial intervention, are essential measures for preserving and enhancing soil quality. To address this problem in view of stubble burning, field experiments were conducted in rice-rice (variety Swarna) cropping systems under lowland conditions, wherein the following different residue management practices were adopted viz., conventional cultivation (CC), residue incorporation (RI @ 6 t paddy straw ha-1), residue retention (RR @6 t paddy straw ha-1), and zero tillage (ZT). In this experiment, two microbial products i.e. solid microbial consortium (SMC) at 2.0 kg ha-1) and capsule (10 numbers ha-1), were evaluated in both Rabi (dry) and Kharif (wet) seasons under different residue management practices. The results on soil microbial properties showed that application of either SMC or capsule based formulation could significantly improve the soil organic carbon (SOC) content in ZT (9.51 g/kg), followed by RI (9.36 g/kg), and RR (9.34 g/kg) as compared to CC (7.61 g/kg). There were significant differences in the soil functional properties (AcP, AkP, FDA, and DHA) with microbial interventions across all residue management practices. SOC was significantly positive correlated with cellulase (R2 = 0.64, p < 0.001), ß-glucosidase (R2 = 0.61, p < 0.001), and laccase (R2 = 0.66, p < 0.001) activity; however, the regression coefficients varied significantly with microbial intervention. Moreover, the availability of N, P, and K in soil was significantly (p < 0.05) improved under microbial treatments with either RR or RI practices. Among the different methods of residues management practices, RI with microbial intervention registered a consistent yield improvement (8.4-17.8%) compared to conventional practices with microbial intervention. The present findings prove that the application of decomposing microbial consortia for in-situ rice residue management under field conditions significantly enhances soil quality and crop yield compared to conventional practices.

Phage and phage cocktails formulations.

Antibiotic-resistant bacterial infection is a major global problem and can be life-threatening. Bacteriophages or phages can be substituted choice over traditional antibiotics treatments. Phages are natural obligate parasites viruses of bacteria, and they can infect and kill antibiotic-sensitive and -resistant bacteria. Further, phages can be utilised as antibacterial agents against various kinds of bacterial infectious diseases. As compared to antibiotics, phages can show a more variety of modes of action and can also be safe in several cases. Phages as a mixture (cocktail) of viral strains are usually used in clinical practices. Generally, to propagate phage cocktails, the individual phage is grown and then mixed to prepare phage cocktails. Antibiotic resistance and biofilm formation can be controlled through formulating phage cocktails that comprise phages infecting single species or by combining phages with non-phages (antibiotics), which may result in a broad spectrum of activity. This chapter briefly highlights the formulations and application of phage cocktails, which are being used to treat various bacterial infections.

Unlocking therapeutic potential: integration of drug repurposing and immunotherapy for various disease targeting.

Drug repurposing, also known as drug repositioning, entails the application of pre-approved or formerly assessed drugs having potentially functional therapeutic amalgams for curing various disorders or disease conditions distinctive from their original remedial indication. It has surfaced as a substitute for the development of drugs for treating cancer, cardiovascular diseases, neurodegenerative disorders, and various infectious diseases like Covid-19. Although the earlier lines of findings in this area were serendipitous, recent advancements are based on patient centered approaches following systematic, translational, drug targeting practices that explore pathophysiological ailment mechanisms. The presence of definite information and numerous records with respect to beneficial properties, harmfulness, and pharmacologic characteristics of repurposed drugs increase the chances of approval in the clinical trial stages. The last few years have showcased the successful emergence of repurposed drug immunotherapy in treating various diseases. In this light, the present review emphasises on incorporation of drug repositioning with Immunotherapy targeted for several disorders.

Phage for treatment of Vibrio cholerae infection.

Bacteriophages (or "phages") are ubiquitous and the amplest biological entities on our planet. It is a natural enemy of bacteria. Cholera is one of the most known diseases to cause multiple pandemics around the world, killing millions of people. The pathogen of cholera is Vibrio species. Up until the emergence of multidrug resistance, preventive therapeutics like antibiotics were the most effective means of battling bacteria. Globally, one of the most significant challenges in treating microbial infections is the development of drug-resistant strains. Based on their antibacterial properties and unique characteristics, phages are being comprehensively evaluated taxonomically. Moreover, phage-based vaccination is evolving as one of the most encouraging preventive approaches. Due to this, its related research got remarkable recognition. However, due to the rapid emergence of bacterial resistance to antibiotics, the use of phages (phage therapy) could be a major motive for research because the most promising solution lies in bacteriophages. This chapter briefly highlights the promising use of bacteriophages to combat Vibrio-related infectious diseases.

Applications of bioinformatics in epigenetics.

Epigenetic modifications such as DNA methylation, post-translational chromatin modifications and non-coding RNA-mediated mechanisms are responsible for epigenetic inheritance. Change in gene expression due to these epigenetic modifications are responsible for new traits in different organisms leading to various diseases including cancer, diabetic kidney disease (DKD), diabetic nephropathy (DN) and renal fibrosis. Bioinformatics is an effective approach for epigenomic profiling. These epigenomic data can be analyzed by a large number of bioinformatics tools and software. Many databases are available online, which comprises huge amount of information regarding these modifications. Recent methodologies include many sequencing and analytical techniques to extrapolate different types of epigenetic data. This data can be used to design drugs against diseases linked to epigenetic modifications. This chapter briefly highlights different epigenetics databases (MethDB, REBASE, Pubmeth, MethPrimerDB, Histone Database, ChromDB, MeInfoText database, EpimiR, Methylome DB, and dbHiMo), and tools (compEpiTools, CpGProD, MethBlAST, EpiExplorer, and BiQ analyzer), which are being utilized to retrieve the data and mechanistically analysis of epigenetics modifications.

Epigenetics in renal diseases.

With aging, prevalence of obesity, hypertension, diabetes and renal diseases have increased globally. Over the last two decades, the prevalence of renal diseases has been intensely increasing. Renal disease and renal programming are regulated by epigenetic modifications like DNA methylation and histone modifications. Environmental factors have significant role in the pathophysiology of renal disease progression. Understanding the potential of epigenetic regulation of gene expression may be useful in renal disease prognosis, diagnosis and provides novel therapeutic measures. In a nutshell, this chapter talks about the role of epigenetic mechanisms-DNA methylation, histone modification, and noncoding RNA in different renal diseases. These include diabetic kidney disease, diabetic nephropathy, renal fibrosis, etc.

Insight into epigenetics and human diseases.

The most eminent research of the 21st century whirls around the epigenetic and the variability of DNA sequences in humans. The reciprocity between the epigenetic changes and the exogenous factors drives an influence on the inheritance biology and gene expression both inter-generationally and trans-generationally. Chromatin level modifications like DNA methylation, histone modifications or changes in transcripts functions either at transcription level or translational level pave the way for certain diseases or cancer in humans. The ability of epigenetics to explain the processes of various diseases has been demonstrated by recent epigenetic studies. Multidisciplinary therapeutic strategies were developed in order to analyse how epigenetic elements interact with different disease pathways. In this chapter we summarize how an organism may be predisposed to certain diseases by exposure to environmental variables such as chemicals, medications, stress, or infections during particular, vulnerable phases of life, and the epigenetic component may influence some of the diseases in humans.

State-of-the-art techniques to study epigenetics.

The epigenome consists of all the epigenetic alterations like DNA methylation, the histone modifications and non-coding RNAs which change the gene expression and have a role in diseases like cancer and other processes. Epigenetic modifications can control gene expression through variable gene activity at various levels which affects various cellular phenomenon such as cell differentiations, variability, morphogenesis, and the adaptability of an organism. Various factors such as food, pollutants, drugs, stress etc., impact the epigenome. Epigenetic mechanisms mainly involve various post-translational alteration of histones and DNA methylation. Numerous methods have been utilized to study these epigenetic marks. Various histone modifications and binding of histone modifier proteins can be analyzed using chromatin immunoprecipitation (ChIP) which is one of broadly utilized method. Other modified forms of the ChIP have been developed such as reverse chromatin immunoprecipitation (R-ChIP); sequential ChIP (ChIP-re-ChIP) and some high-throughput modified forms of ChIP such as ChIP-seq and ChIP-on-chip. Another epigenetic mechanism is DNA methylation, in which DNA methyltransferases (DNMTs) add a methyl group to the C-5 position of the cytosine. Bisulfite sequencing is the oldest and usually utilized method to measure the DNA methylation status. Other techniques have been established are whole genome bisulfite sequencing (WGBS), methylated DNA immune-precipitation based methods (MeDIP), methylation sensitive restriction enzyme digestion followed by sequencing (MRE-seq) and methylation BeadChip to study the methylome. This chapter briefly discusses the key principles and methods used to study epigenetics in health and disease conditions.

Cleaner production of essential oils from Indian basil, lemongrass and coriander leaves using ultrasonic and ohmic heating pre-treatment systems.

Indian basil (Ocimum basillicum), lemongrass (Cymbopogon flexuosus) and coriander (Coriandrum sativum) leaves are a good source of aromatic oils; however, their extraction volume is low. Hence, two pre-treatment systems (ohmic-heating and ultrasonic) were devised for extraction of essential oils (EO) from the leaves of these three plant spp., which consequently enhanced the EO yield and saved the time and energy. First of all, an experimental set-up was developed for ohmic-heating pre-treatment which was subjected to the optimization of electric conductivity of lemongrass and coriander leaves at 26.25 V/cm and for Indian basil at 22.5 V/cm voltage gradient. An Experimental setup was also developed for ohmic heating-assisted hydro-distillation (OHD). Finally, conventional Clevenger hydro-distillation (CHD), OHD, ultrasonic-assisted conventional hydro-distillation (UACHD) and ultrasonic-assisted ohmic-heating hydro-distillation (UAOHD) methods were evaluated for their effectiveness in the extraction of the EOs. The OHD took 3.5 h time with 410 W power consumption compared to 5 h time and 500 W power consumption in CHD of sleeted leaves. Likewise, a saving of ~ 86% in time and 74% in energy consumption was observed for EO extraction through UAOHD over CHD. Quantity of EOs extracted from all three aromatic plant spp. leaves followed the trend of UAOHD > UACHD > OHD > CHD methods, respectively. Overall, ultrasonic pre-treatment coupled with ohmic-heating assisted hydro-distillation (UAOHD) proved as an innovative and effective clean EO extraction technology which took shorter extraction time and lesser energy consumption with better EO yield over the UACHD, OHD and CHD methods from the leaves of Indian basil, lemongrass and coriander.

Phage engineering and phage-assisted CRISPR-Cas delivery to combat multidrug-resistant pathogens.

Antibiotic resistance ranks among the top threats to humanity. Due to the frequent use of antibiotics, society is facing a high prevalence of multidrug resistant pathogens, which have managed to evolve mechanisms that help them evade the last line of therapeutics. An alternative to antibiotics could involve the use of bacteriophages (phages), which are the natural predators of bacterial cells. In earlier times, phages were implemented as therapeutic agents for a century but were mainly replaced with antibiotics, and considering the menace of antimicrobial resistance, it might again become of interest due to the increasing threat of antibiotic resistance among pathogens. The current understanding of phage biology and clustered regularly interspaced short palindromic repeats (CRISPR) assisted phage genome engineering techniques have facilitated to generate phage variants with unique therapeutic values. In this review, we briefly explain strategies to engineer bacteriophages. Next, we highlight the literature supporting CRISPR-Cas9-assisted phage engineering for effective and more specific targeting of bacterial pathogens. Lastly, we discuss techniques that either help to increase the fitness, specificity, or lytic ability of bacteriophages to control an infection.

Endocytosis and signaling of 5-HT1A receptor.

The neurotransmitter serotonin (also known as 5-hydroxytryptamine, 5-HT) regulates many important physiological as well as pathological functions in the body like psychoemotional, sensation, blood circulation, food intake, autonomic, memory, sleep, pain, etc. 5-HT binds to its receptor 5-HT1A to initiate GTP exchange at the Gi/o protein, which activates the receptor G protein complex. G protein subunits attach to different effectors and generate various responses, such as inhibition of adenyl cyclase enzyme and regulates the opening of Ca++ and K+ ion channels. Activated signalling cascades activate protein kinase C (PKC) (a second messenger), which further induces the detachment of Gßγ-dependent receptor signaling and leads to 5-HT1A internalization. After internalization, 5-HT1A receptor attaches to the Ras-ERK1/2 pathway. The receptor further trafficks to the lysosome for degradation. Receptor skips the trafficking to the lysosomal compartments and undergoes dephosphorylation. Dephosphorylated receptors now recycled back to the cell membrane. In this chapter, we have discussed the internalization, trafficking and signaling of the 5-HT1A receptor.

Glutamate receptor endocytosis and signaling in neurological conditions.

The non-essential amino acid glutamate acts as a major excitatory neurotransmitter and plays a significant role in the central nervous system (CNS). It binds with two different types of receptors, ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs), responsible for the postsynaptic excitation of neurons. They are important for memory, neural development and communication, and learning. Endocytosis and subcellular trafficking of the receptor are essential for the regulation of receptor expression on the cell membrane and excitation of the cells. The endocytosis and trafficking of the receptor are dependent on its type, ligand, agonist, and antagonist present. This chapter discusses the types of glutamate receptors, their subtypes, and the regulation of their internalization and trafficking. The roles of glutamate receptors in neurological diseases are also briefly discussed.

Amyloid precursor protein in Alzheimer's disease.

Amyloid precursor protein (APP) is a membrane protein expressed in several tissues. The occurrence of APP is predominant in synapses of nerve cells. It acts as a cell surface receptor and plays a vital role as a regulator of synapse formation, iron export and neural plasticity. It is encoded by the APP gene that is regulated by substrate presentation. APP is a precursor protein activated by proteolytic cleavage and thereby generating amyloid beta (Aß) peptides which eventually form amyloid plaques that accumulate in Alzheimer's disease patients' brains. In this chapter, we highlight basic mechanism, structure, expression patterns and cleavage of amyloid plaques, and its diagnosis and potential treatment for Alzheimer's disease.

Receptor biology: Challenges and opportunities.

Receptor biology provides a great opportunity to understand the ligand-receptor signaling involved in health and disease processes. Receptor endocytosis and signaling play a vital role in health conditions. Receptor-based signaling is the main form of communication between cells and cells with the environment. However, if any irregularities happen during these events, the consequences of pathophysiological conditions occur. Various methods are utilized to know structure, function, and regulation of receptor proteins. Further, live-cell imaging and genetic manipulations have aided in the understanding of receptor internalization, subcellular trafficking, signaling, metabolic degradation, etc. Understanding the genetics, biochemistry, and physiology of receptors and ligands is very helpful to explore various aspects such as prognosis, diagnosis, and treatment of disease. However, there are enormous challenges that exist to explore receptor biology further. This chapter briefly discusses the current challenges and emerging opportunities of receptor biology.