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.

Development of Prediction Models for Soil Nitrogen Management Based on Electrical Conductivity and Moisture Content.

A study was conducted with the goal of developing an algorithm for use in sensors to monitor available soil N. For this purpose, three different soils were selected. The soils were studied for electrical conductivity (EC) at four different moisture levels and four levels of N. The selection of moisture levels was based on optimum moisture levels between tillage moisture and field capacity. The results revealed a significant relationship between electrical conductivity and moisture level of the soil as well as between electrical conductivity and soil N content. Based on these relations, a polynomial model was developed between the EC of each selected soil sample and moisture content as well as N levels. The regression model for moisture content-based EC determination had coefficients of determination of 0.985, 0.988, and 0.981 for clay loam, sandy loam, and sandy loam soils, respectively. Similarly, the regression model for N content-based EC determination had coefficients of determination of 0.9832, 0.9, and 0.99 for clay loam, sandy loam, and sandy loam soils, respectively. An algorithm developed using a polynomial relationship between the EC of each selected soil sample at all moisture and N levels can be used to develop a sensor for site-specific N application.

Ligand-Dependent Downregulation of Guanylyl Cyclase/Natriuretic Peptide Receptor-A: Role of miR-128 and miR-195.

Cardiac hormones act on the regulation of blood pressure (BP) and cardiovascular homeostasis. These hormones include atrial and brain natriuretic peptides (ANP, BNP) and activate natriuretic peptide receptor-A (NPRA), which enhance natriuresis, diuresis, and vasorelaxation. In this study, we established the ANP-dependent homologous downregulation of NPRA using human embryonic kidney-293 (HEK-293) cells expressing recombinant receptor and MA-10 cells harboring native endogenous NPRA. The prolonged pretreatment of cells with ANP caused a time- and dose-dependent decrease in 125I-ANP binding, Guanylyl cyclase (GC) activity of receptor, and intracellular accumulation of cGMP leading to downregulation of NPRA. Treatment with ANP (100 nM) for 12 h led to an 80% decrease in 125I-ANP binding to its receptor, and BNP decreased it by 62%. Neither 100 nM c-ANF (truncated ANF) nor C-type natriuretic peptide (CNP) had any effect. ANP (100 nM) treatment also decreased GC activity by 68% and intracellular accumulation cGMP levels by 45%, while the NPRA antagonist A71915 (1 µM) almost completely blocked ANP-dependent downregulation of NPRA. Treatment with the protein kinase G (PKG) stimulator 8-(4-chlorophenylthio)-cGMP (CPT-cGMP) (1 µM) caused a significant increase in 125I-ANP binding, whereas the PKG inhibitor KT 5823 (1 µM) potentiated the effect of ANP on the downregulation of NPRA. The transfection of miR-128 significantly reduced NPRA protein levels by threefold compared to control cells. These results suggest that ligand-dependent mechanisms play important roles in the downregulation of NPRA in target cells.

A Novel Approach for Development and Evaluation of LiDAR Navigated Electronic Maize Seeding System Using Check Row Quality Index.

Crop geometry plays a vital role in ensuring proper plant growth and yield. Check row planting allows adequate space for weeding in both direction and allowing sunlight down to the bottom of the crop. Therefore, a light detection and ranging (LiDAR) navigated electronic seed metering system for check row planting of maize seeds was developed. The system is comprised of a LiDAR-based distance measurement unit, electronic seed metering mechanism and a wireless communication system. The electronic seed metering mechanism was evaluated in the laboratory for five different cell sizes (8.80, 9.73, 10.82, 11.90 and 12.83 mm) and linear cell speed (89.15, 99.46, 111.44, 123.41 and 133.72 mm·s-1). The research shows the optimised values for the cell size and linear speed of cell were found to be 11.90 mm and 99.46 mm·s-1 respectively. A light dependent resistor (LDR) and light emitting diode (LED)-based seed flow sensing system was developed to measure the lag time of seed flow from seed metering box to bottom of seed tube. The average lag time of seed fall was observed as 251.2 ± 5.39 ms at an optimised linear speed of cell of 99.46 mm·s-1 and forward speed of 2 km·h-1. This lag time was minimized by advancing the seed drop on the basis of forward speed of tractor, lag time and targeted position. A check row quality index (ICRQ) was developed to evaluate check row planter. While evaluating the developed system at different forward speeds (i.e., 2, 3 and 5 km·h-1), higher standard deviation (14.14%) of check row quality index was observed at forward speed of 5 km·h-1.

Genetic disruption of Npr1 depletes regulatory T cells and provokes high levels of proinflammatory cytokines and fibrosis in the kidneys of female mutant mice.

The present study was designed to determine the effects of gene knockout of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) on immunogenic responses affecting kidney function and blood pressure (BP) in Npr1 (coding for GC-A/NPRA)-null mutant mice. We used female Npr1 gene-disrupted (Npr1-/-, 0 copy), heterozygous (Npr1+/-, 1 copy), wild-type (Npr1+/+, 2 copy), and gene-duplicated (Npr1++/++, 4 copy) mice. Expression levels of Toll-like receptor (TLR)2/TLR4 mRNA were increased 4- to 5-fold in 1-copy mice and 6- to 10-fold in 0-copy mice; protein levels were increased 2.5- to 3-fold in 1-copy mice and 4- to 5-fold in 0-copy mice. Expression of proinflammatory cytokines and BP was significantly elevated in 1-copy and 0-copy mice compared with 2-copy and 4-copy mice. In addition, 0-copy and 1-copy mice exhibited drastic reductions in regulatory T cells (Tregs). After rapamycin treatment, Tregs were increased by 17% (P < 0.001) in 0-copy mice and 8% (P < 0.001) in 1-copy mice. Renal mRNA and protein levels of TLR2 and TLR4 were decreased by 70% in 0-copy mice and 50% in 1-copy mice. There were significantly higher levels of Tregs and very low levels of TLR2/TLR4 expression in 4-copy mice (P < 0.001). These findings indicate that the disruption of Npr1 in female mice triggers renal immunogenic pathways, which transactivate the expression of proinflammatory cytokines and renal fibrosis with elevated BP in mutant animals. The data suggest that rapamycin treatment attenuates proinflammatory cytokine expression, dramatically increases anti-inflammatory cytokines, and substantially reduces BP and renal fibrosis in mutant animals.

A prospective study of non-tuberculous mycobacterial disease among tuberculosis suspects at a tertiary care centre in north India.

Background & objectives: The burden of non-tuberculous mycobacterial (NTM) disease is increasing worldwide. The disease shares clinicoradiological features with tuberculosis (TB), Nocardia and several fungal diseases, and its diagnosis is frequently delayed. The present study was performed to determine the frequency of NTM disease among TB suspects in a tertiary care centre in north India. Methods: In this prospective study, mycobacterial culture isolates from pulmonary and extrapulmonary specimens among TB suspects were tested with immunochromatographic assay (ICA). All ICA-negative isolates were considered as NTM suspects and further subjected to 16S-23S rRNA internal transcribed spacer gene sequencing for confirmation and species identification. Patients with active disease were treated with drug regimen as per the identified NTM species. Follow up of patients was done to determine clinical, radiological and microbiological outcomes. Results: Of the 5409 TB suspects, 42 (0.77%) were diagnosed with NTM disease. Patients with active disease consenting for treatment were treated and followed up. Thirty four patients had NTM pulmonary disease (NTM-PD) and the remaining eight had extrapulmonary NTM (EP-NTM) disease. Mycobacterium intracellulare and M. abscessus, respectively, were most frequently isolated from NTM-PD and EP-NTM patients. Fifteen NTM-PD and seven EP-NTM patients successfully completed the treatment. Ten patients died due to unrelated causes, five were lost to follow up and another four declined the treatment. Interpretation & conclusions: Our study showed that the frequency of NTM disease was low among TB suspects at a large tertiary care centre in north India and this finding was similar to other Indian studies. More studies need to be done in other parts of the country to know the geographical variation in NTM disease, if any.

Clathrin-dependent internalization, signaling, and metabolic processing of guanylyl cyclase/natriuretic peptide receptor-A.

Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP), have pivotal roles in renal hemodynamics, neuroendocrine signaling, blood pressure regulation, and cardiovascular homeostasis. Binding of ANP and BNP to the guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) induces rapid internalization and trafficking of the receptor via endolysosomal compartments, with concurrent generation of cGMP. However, the mechanisms of the endocytotic processes of NPRA are not well understood. The present study, using 125I-ANP binding assay and confocal microscopy, examined the function of dynamin in the internalization of NPRA in stably transfected human embryonic kidney-293 (HEK-293) cells. Treatment of recombinant HEK-293 cells with ANP time-dependently accelerated the internalization of receptor from the cell surface to the cell interior. However, the internalization of ligand-receptor complexes of NPRA was drastically decreased by the specific inhibitors of clathrin- and dynamin-dependent receptor internalization, almost 85% by monodansylcadaverine, 80% by chlorpromazine, and 90% by mutant dynamin, which are specific blockers of endocytic vesicle formation. Visualizing the internalization of NPRA and enhanced GFP-tagged NPRA in HEK-293 cells by confocal microscopy demonstrated the formation of endocytic vesicles after 5 min of ANP treatment; this effect was blocked by the inhibitors of clathrin and by mutant dynamin construct. Our results suggest that NPRA undergoes internalization via clathrin-mediated endocytosis as part of its normal itinerary, including trafficking, signaling, and metabolic degradation.

Retinoic acid and sodium butyrate suppress the cardiac expression of hypertrophic markers and proinflammatory mediators in Npr1 gene-disrupted haplotype mice.

The objective of the present study was to examine the genetically determined differences in the natriuretic peptide receptor-A (NPRA) gene (Npr1) copies affecting the expression of cardiac hypertrophic markers, proinflammatory mediators, and matrix metalloproteinases (MMPs) in a gene-dose-dependent manner. We determined whether stimulation of Npr1 by all-trans retinoic acid (RA) and histone deacetylase (HDAC) inhibitor sodium butyric acid (SB) suppress the expression of cardiac disease markers. In the present study, we utilized Npr1 gene-disrupted heterozygous (Npr1(+/-), 1-copy), wild-type (Npr1(+/+), 2-copy), gene-duplicated (Npr1(++/+), 3-copy) mice, which were treated intraperitoneally with RA, SB, and a combination of RA/SB, a hybrid drug (HB) for 2 wk. Untreated 1-copy mice showed significantly increased heart weight-body weight (HW/BW) ratio, blood pressure, hypertrophic markers, including beta-myosin heavy chain (ß-MHC) and proto-oncogenes (c-fos and c-jun), proinflammatory mediator nuclear factor kappa B (NF-κB), and MMPs (MMP-2, MMP-9) compared with 2-copy and 3-copy mice. The heterozygous (haplotype) 1-copy mice treated with RA, SB, or HB, exhibited significant reduction in the expression of ß-MHC, c-fos, c-jun, NF-κB, MMP-2, and MMP-9. In drug-treated animals, the activity and expression levels of HDAC were significantly reduced and histone acetyltransferase activity and expression levels were increased. The drug treatments significantly increased the fractional shortening and reduced the systolic and diastolic parameters of the Npr1(+/-) mice hearts. Together, the present results demonstrate that a decreased Npr1 copy number enhanced the expression of hypertrophic markers, proinflammatory mediators, and MMPs, whereas an increased Npr1 repressed the cardiac disease markers in a gene-dose-dependent manner.

Role of FQQI motif in the internalization, trafficking, and signaling of guanylyl-cyclase/natriuretic peptide receptor-A in cultured murine mesangial cells.

Binding of the cardiac hormone atrial natriuretic peptide (ANP) to transmembrane guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), produces the intracellular second messenger cGMP in target cells. To delineate the critical role of an endocytic signal in intracellular sorting of the receptor, we have identified a FQQI (Phe(790), Gln(791), Gln(792), and Ile(793)) motif in the carboxyl-terminal region of NPRA. Mouse mesangial cells (MMCs) were transiently transfected with the enhanced green fluorescence protein (eGFP)-tagged wild-type (WT) and mutant constructs of eGFP-NPRA. The mutation FQQI/AAAA, in the eGFP-NPRA cDNA sequence, markedly attenuated the internalization of mutant receptors by almost 49% compared with the WT receptor. Interestingly, we show that the µ1B subunit of adaptor protein-1 binds directly to a phenylalanine-based FQQI motif in the cytoplasmic tail of the receptor. However, subcellular trafficking indicated that immunofluorescence colocalization of the mutated receptor with early endosome antigen-1 (EEA-1), lysosome-associated membrane protein-1 (LAMP-1), and Rab 11 marker was decreased by 57% in early endosomes, 48% in lysosomes, and 42% in recycling endosomes, respectively, compared with the WT receptor in MMCs. The receptor containing the mutated motif (FQQI/AAAA) also produced a significantly decreased level of intracellular cGMP during subcellular trafficking than the WT receptor. The coimmunoprecipitation assay confirmed a decreased level of colocalization of the mutant receptor with subcellular compartments during endocytic processes. The results suggest that the FQQI motif is essential for the internalization and subcellular trafficking of NPRA during the hormone signaling process in intact MMCs.

All-trans retinoic acid and sodium butyrate enhance natriuretic peptide receptor a gene transcription: role of histone modification.

The objective of the present study was to delineate the mechanisms of GC-A/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) expression in vivo. We used all-trans retinoic acid (ATRA) and histone deacetylase (HDAC) inhibitor, sodium butyrate (NaBu) to examine the expression and function of Npr1 using gene-disrupted heterozygous (1-copy; +/-), wild-type (2-copy; +/+), and gene-duplicated heterozygous (3-copy; ++/+) mice. Npr1(+/-) mice exhibited increased renal HDAC and reduced histone acetyltransferase (HAT) activity; on the contrary, Npr1(++/+) mice showed decreased HDAC and enhanced HAT activity compared with Npr1(+)(/+) mice. ATRA and NaBu promoted global acetylation of histones H3-K9/14 and H4-K12, reduced methylation of H3-K9 and H3-K27, and enriched accumulation of active chromatin marks at the Npr1 promoter. A combination of ATRA-NaBu promoted recruitment of activator-complex containing E26 transformation-specific 1, retinoic acid receptor α, and HATs (p300 and p300/cAMP response element-binding protein-binding protein-associated factor) at the Npr1 promoter, and significantly increased renal NPRA expression, GC activity, and cGMP levels. Untreated 1-copy mice showed significantly increased systolic blood pressure and renal expression of α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) compared with 2- and 3-copy mice. Treatment with ATRA and NaBu synergistically attenuated the expression of α-SMA and PCNA and reduced systolic blood pressure in Npr1(+/-) mice. Our findings demonstrate that epigenetic upregulation of Npr1 gene transcription by ATRA and NaBu leads to attenuation of renal fibrotic markers and systolic blood pressure in mice with reduced Npr1 gene copy number, which will have important implications in prevention and treatment of hypertension-related renal pathophysiological conditions.

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.

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.

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.

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.

Endocytosis and signaling of angiotensin II type 1 receptor.

A vasoactive octapeptide angiotensin II (Ang II) hormone is the key regulator of the renin-angiotensin system (RAS). It binds with the two different plasma membrane receptors like angiotensin II type 1 (AT1) and type 2 (AT2) and consequence various biological responses occur. Further, AT1 has two subtypes such as AT1A and AT1B. These angiotensin receptors are classified to be G protein-coupled receptors (GPCRs). The main constituent of RAS is the AT1 receptor (AT1R), and its activation, signal transduction, and regulation have been extensively studied. After Ang II stimulation, the ligand-receptor complexes internalized and trafficked through the early endosome, recycling endosome, and some receptors skipped the recycling endosome and trafficked to the lysosome for metabolic degradation. Moreover, some short sequence motifs located in the carboxyl-terminus (CT) of the receptor play a vital role in the internalization, phosphorylation, subcellular trafficking, signaling, and desensitization. Furthermore, in endocytosis, the various proteins interact with the CT region of the receptor. This chapter highlights the basic mechanism of AT1 receptor internalization, trafficking and signaling in both physiological and pathophysiological conditions.

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.

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.

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.

An overview of receptor endocytosis and signaling.

Endocytosis is a cellular process which mediates receptor internalization, nutrient uptake, and the regulation of cell signaling. Microorganisms (many bacteria and viruses) and toxins also use the same process and enter the cells. Generally, endocytosis is considered in the three forms such as phagocytosis (cell eating), pinocytosis (cell drinking), and highly selective receptor-mediated endocytosis (clathrin-dependent and independent). Several endocytic routes exist in an analogous, achieving diverse functions. Most studies on endocytosis have used transformed cells in culture. To visualize the receptor internalization, trafficking, and signaling in subcellular organelles, a green fluorescent protein-tagged receptor has been utilized. It also helps to visualize the endocytosis effects in live-cell imaging. Confocal laser microscopy increases our understanding of receptor endocytosis and signaling. Site-directed mutagenesis studies demonstrated that many short-sequence motifs of the cytoplasmic domain of receptors significantly play a vital role in receptor internalization, subcellular trafficking, and signaling. However, other factors also regulate receptor internalization through clathrin-coated vesicles. Receptor endocytosis can occur through clathrin-dependent and clathrin-independent pathways. This chapter briefly discusses the internalization, trafficking, and signaling of various receptors in normal conditions. In addition, it also highlights the malfunction of the receptor in disease conditions.

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.