Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders.

TRPM8 is a non-selective cation channel that is expressed in several tissues and cells and also has a unique property to be activated by low-temperature. In this work, we have analyzed the conservation of amino acids that are present in the lipid-water-interface (LWI) region of TRPM8, the region which experiences a microenvironment near the membrane surface. We demonstrate that the amino acids present in the LWI region are more conserved than the transmembrane or even full-length TRPM8, suggesting strong selection pressure in these residues. TRPM8 also has several conserved cholesterol-binding motifs where cholesterol can bind in different modes and energies. We suggest that mutations and/or physiological conditions can potentially alter these TRPM8-cholesterol complexes and can lead to physiological disorders or even apparently irreversible diseases such as cancer and neurodegeneration.

ELONGATED HYPOCOTYL 5 (HY5) and POPEYE (PYE) regulate intercellular iron transport in plants.

Plants maintain iron (Fe) homeostasis under varying environmental conditions by balancing processes such as Fe uptake, transport and storage. In Arabidopsis, POPEYE (PYE), a basic helix-loop-helix transcription factor (TF), has been shown to play a crucial role in regulating this balance. In recent years, the mechanisms regulating Fe uptake have been well established but the upstream transcriptional regulators of Fe transport and storage are still poorly understood. In this study, we report that ELONGATED HYPOCOTYL5 (HY5), a basic leucine zipper (bZIP) TF which has recently been shown to play a crucial role in Fe homeostasis, interacts with PYE. Molecular, genetic and biochemical approaches revealed that PYE and HY5 have overlapping as well as some distinct roles in the regulation of Fe deficiency response. We found that HY5 and PYE both act as a repressor of Fe transport genes such as YSL3, FRD3, NPF5.9, YSL2, NAS4 and OPT3. HY5 was found to directly bind on the promoter of these genes and regulate intercellular Fe transport. Further analysis revealed that HY5 and PYE directly interact at the same region on PYE and NAS4 promoter. Overall, this study revealed that HY5 regulates Fe homeostasis by physically interacting with PYE as well as independently.

Elemental profiling of agricultural soil in Hoshiarpur utilizing analytical techniques.

Our study aimed to assess the soil quality in Punjab's Hoshiarpur district through a meticulous analysis of nutrient and elemental composition. Using a variety of analytical techniques, including Neutron Activation Analysis (NAA), external Particle-induced Gamma-ray Emission (PIGE) an Ion beam analysis Technique, and energy-dispersive X-ray fluorescence (ED-XRF), we delved into soil characterization for 22 agricultural soil samples in the Punjab region. Within the NAA framework, utilizing the Pneumatic Carrier Facility and the self-serve facility at Dhruva reactor in Mumbai, a brief 1-min irradiation procedure identified pivotal elements-Na, Mg, V, Al, Mn, and K. Conversely, an extended neutron irradiation process of approximately 4 h within the self-serve facility enabled the estimation of nearly 12 elements, including Rare Earth Elements (REEs), Transition elements, and other significant elements. The external PIGE technique quantified low Z elements (Na, Mg, Al, and Si), contributing to our analytical arsenal. Rigorously validating both NAA and PIGE methodologies, we compared results meticulously against established geological standard reference materials-specifically USGS RGM-1 and USGS AGV-1.Instrumental in elemental analysis, ED-XRF spectroscopy fortified our investigative endeavors by quick assessment of ten crucial elements. The elemental analysis revealed notable accumulations of Mn and Zn in the soil, surpassing the suggested permissible limits, whereas Co, Cr, and Pb were found to be within the recommended thresholds set by WHO/UNEP. Beyond elemental profiling, our study extended to estimate the accumulation levels of various elements utilizing ecological risk factors such as Contamination Factor, Potential Ecological Risk Index, Pollution Load Index, and Geoaccumulation Factor. Our findings highlighted significant accumulation of REEs including La, Sm and Yb.. This evaluation sheds new light on the interplay between soil composition and environmental health, emphasizing the need for advanced accessible agricultural technologies to prevent and forecast contaminant discharge in arable soil. This commitment aligns with our broader goal of advancing sustainable practices in soil management.

Time-efficient etching of LR-115 SSNTD film for indoor radon, thoron quantification.

LR-115 Solid State Nuclear Track Detector (SSNTD) is commonly utilized for quantifying indoor radon-thoron levels, by tallying the tracks formed in the films by exposure to these gases. Conventionally, sodium hydroxide (NaOH) is used to etch LR-115 films for 90 min at 60°C. However, this study suggests a time-efficient alternative approach utilizing potassium hydroxide (KOH) as the etchant. In an initial investigation, the bulk etch rates of KOH were examined at different normalities and temperatures, revealing that KOH exhibited nearly double the bulk etch rates compared to NaOH. Subsequently, a specially designed controlled experiment was conducted to assess the efficacy of the technique by enumerating the tracks generated in the films. Both etchants demonstrated very similar track counts for identical controlled exposures, indicating the reliability of the method. A consistent behavior was observed in the real-case scenario of LR-115 films exposed indoors to alpha particles from radon and its decay products. In both experiments, the etching with KOH for 45 min gave track densities comparable to standard NaOH etching for 90 min, highlighting the time efficiency of this method. Investigations were carried out into track shape and size features, aspects crucial to the measurement technique, using microscopic imaging of samples treated with both etchants. Strikingly similar track shapes and sizes were observed, affirming the consistency in the track measurement technique. Collectively, these findings suggest that KOH etchant reduces the etching time, presenting itself as a time-efficient method for quantifying radon and thoron track density.

Modulation of TRPM8 alters the phagocytic activity of microglia and induces changes in sub-cellular organelle functions.

In this work, we investigated the presence and function of TRPM8, a non-selective and cold-sensitive Ca2+-permeable ion channel in the primary microglia cell as well as in microglia cell line BV2. We demonstrate that primary microglia as well as BV2 express TRPM8 endogenously. Both pharmacological activation or inhibition of TRPM8 causes enhanced uptake of bacterial particles at early time points of infection. In BV2, TRPM8 activation and/or LPS-signaling alters its surface expression and cytosolic ROS production. TRPM8 modulation in the absence and presence of LPS causes differential regulation of cytosolic pH and lysosomal pH. Notably, TRPM8 modulation also alters the correlation between lysosomal pH and cytosolic pH depending on TRPM8 modulation and the presence or absence of LPS. Collectively our data suggest that TRPM8 is involved in the regulation of subcellular organelle, i.e. mitochondrial and lysosomal functions. Data also suggest that primarily TRPM8 activation, but often deviation from endogenous TRPM8 function is linked with better innate immune function mediated by microglial cells. We suggest that TRPM8-mediated regulations of sub-cellular organelle functions are more context-dependent manner. Such understanding is relevant in the context of microglial cell functions and innate immunity.

Role of jasmonate signaling in the regulation of plant responses to nutrient deficiency.

Phytohormones regulate plant growth and development by integrating various internal developmental cues with external environmental conditions. Jasmonic acid (JA) is an oxylipin-derived phytohormone that modulates the plasticity of plant responses against fluctuating environmental cues. An increasing number of studies have shown that it regulates a wide spectrum of plant physiological and biochemical processes, including reproductive development, primary root growth, root hair development, seed germination, senescence, regeneration, defense against biotic stress such as pathogen infection and herbivory, and mitigation of a number of abiotic stresses such as salinity, drought, high and low temperatures, wounding, excessive UV exposure, limited water availability, and metal(oid)-induced toxicity. Nutrient deficiency is an abiotic stress that adversely affects plant growth, development, and productivity, and JA also plays an important role in regulation of these processes under such conditions. In this review, we summarize recent advances relating to the role of JA and its methyl ester derivative (methyl jasmonate) in modulating responses to nutrient deficiency, to the impact of nutrient status on JA biosynthesis and signaling, and to the crosstalk of JA with other phytohormones in shaping plant growth and development under deficiencies of various mineral elements.

Microstructural, biocompatibility and mechanical investigation of MgHAp and AgHAp: Comparative report.

It is imperative to investigate the effect of addition of different size metallic ions in HAp and study the changes in biocompatibility and mechanical properties. Silver and magnesium ions are two vital ions needed in our body. Silver ions are known to inhibit the microbes, while magnesium ions are known to increase the mechanical properties. The present study reports the comparative properties of MgHAp and AgHAp synthesised by sol-gel wet chemical method. Changes in the morphology, phase analysis, corrosion resistance, dielectric properties, hardness and the thrombus behaviour of HAp doped Ag and Mg ions has been investigated. In this work, we have presented a comparative study of both the metal doped ionsto find which of the ions and which weight percent of the ions can be best suited to be incorporated into the HAp matrix for hard tissue implants. All wt% AgHAp showed the better corrosion resistance than all the MgHAp samples. However, MgHAp showed higher value of hardness in comparison to AgHAp samples. The mechanical strength was found to increase with the increase in Mg wt% in MgHAp but for AgHAp the hardness value decreased with increase in the concentration. The impedance and dielectric loss decreased with increasing frequency for both the samples. Both the ion doped hydroxyapatite showed moderate clotting behaviour as compared to pure HAp. But 2 wt% MgHAp and 4 wt% AgHAp showed better thrombogenic behaviour. It is imperative to investigate the effect of addition of different size metallic ions in HAp and study the changes in biocompatibility and mechanical properties. Silver and magnesium ions are two vital ions needed in our body. Silver ions are known to inhibit the microbes, while magnesium ions are known to increase the mechanical properties. The present study reports the comparative properties of MgHAp and AgHAp synthesised by sol-gel wet chemical method. Changes in the morphology, phase analysis, corrosion resistance, dielectric properties, hardness and the thrombus behaviour of HAp doped Ag and Mg ions has been investigated. In this work we have presented a comparative study of both the metal doped ions to find which of the ions and which weight percent of the ions can be best suited to be incorporated into the HAp matrix for hard tissue implants. All wt% AgHAp showed the better corrosion resistance than all the MgHAp samples. However, MgHAp showed higher value of hardness in comparison to AgHAp samples. The mechanical strength was found to increase with the increase in Mg wt% in MgHAp but for AgHAp the hardness value decreased with increase in the concentration. The impedance and dielectric loss decreased with increasing frequency for both the samples. Both the ion doped hydroxyapatite showed moderate clotting behaviour as compared to pure HAp. But 2 wt% MgHAp and 4 wt% AgHAp showed better thrombogenic behaviour.

Risk factors of osteoporosis in soldiers of the Armed Forces: A cross-sectional study from Western India.

Background: Osteoporosis may result from risk factors such as smoking, alcohol, low body mass index, less physical exercise, and dietary calcium deficiency. The risk of osteoporosis fractures can be reduced with lifestyle changes, which include diet, exercise, and preventing falls. The present study is an effort to measure the burden of risk factors of osteoporosis in adult male soldiers in the Armed Forces. Methods: The present study was a cross-sectional study among serving soldiers in South-Western part of India, and 400 participants consented to be included in the study. After obtaining informed consent, the questionnaire was distributed. Venous blood samples were collected to measure serum calcium, phosphorus, vitamin D, and parathyroid hormone (PTH). Results: The prevalence of vitamin D3 severe deficiency (<10 ng/mL) was 38.5%, and the prevalence of vitamin D3 deficiency (10-19 ng/mL) was 33%. Low serum calcium (<8.4 mg/dL) and serum phosphorus (<2.5 mg/dL) were found among 19.5% and 11.5%, respectively, whereas a raised serum PTH level (>66.5 pg/mL) was seen in 5.5% of the participants. A statistically significant association was found between consumption of milk and milk products and levels of calcium. With a cutoff value of 20 ng/mL for vitamin D3 deficiency, a statistically significant association was found for consumption of fish, physical activity, and sun exposure. Conclusion: A remarkably large percentage of otherwise normal healthy soldiers have deficiency or insufficiency of vitamin D and might be prone to osteoporosis. Despite significant advances in our understanding and management options for male osteoporosis, there still remain important gaps in knowledge which needs to be looked into.

Function and regulation of thermosensitive ion channel TRPV4 in the immune system.

Transient receptor potential vanilloid sub-type 4 (TRPV4) is a six transmembrane protein that acts as a non-selective Ca2+ channel. Notably, TRPV4 is present in almost all animals, from lower eukaryotes to humans and is expressed in diverse tissue and cell types. Accordingly, TRPV4 is endogenously expressed in several types of immune cells that represent both innate and adaptive immune systems of higher organism. TRPV4 is known to be activated by physiological temperature, suggesting that it acts as a molecular temperature sensor and thus plays a key role in temperature-dependent immune activation. It is also activated by diverse endogenous ligands, lipid metabolites, physical and mechanical stimuli. Both expression and function of TRPV4 in various immune cells, including T cells and macrophages, are also modulated by multiple pro- and anti-inflammatory compounds. The results from several laboratories suggest that TRPV4 is involved in the immune activation, a phenomenon with evolutionary significance. Because of its diverse engagement in the neuronal and immune systems, TRPV4 is a potential therapeutic target for several immune-related disorders.

In Silico Evaluation of Natural Flavonoids as a Potential Inhibitor of Coronavirus Disease.

The recent coronavirus disease (COVID-19) outbreak in Wuhan, China, has led to millions of infections and the death of approximately one million people. No targeted therapeutics are currently available, and only a few efficient treatment options are accessible. Many researchers are investigating active compounds from natural plant sources that may inhibit COVID-19 proliferation. Flavonoids are generally present in our diet, as well as traditional medicines and are effective against various diseases. Thus, here, we reviewed the potential of flavonoids against crucial proteins involved in the coronavirus infectious cycle. The fundamentals of coronaviruses, the structures of SARS-CoV-2, and the mechanism of its entry into the host's body have also been discussed. In silico studies have been successfully employed to study the interaction of flavonoids against COVID-19 Mpro, spike protein PLpro, and other interactive sites for its possible inhibition. Recent studies showed that many flavonoids such as hesperidin, amentoflavone, rutin, diosmin, apiin, and many other flavonoids have a higher affinity with Mpro and lower binding energy than currently used drugs such as hydroxylchloroquine, nelfinavir, ritonavir, and lopinavir. Thus, these compounds can be developed as specific therapeutic agents against COVID-19, but need further in vitro and in vivo studies to validate these compounds and pave the way for drug discovery.

Influenza and End-Stage Renal Disease: A Fatal Combination.

Influenza epidemics are a major health care problem in the United States causing significant morbidity and mortality. Influenza can occur in all individuals, but immunocompromized hosts and those with chronic diseases such as end-stage renal disease are more susceptible to its fatal complications. Influenza though is largely preventable with the availability of highly efficacious vaccines. Despite the wide array of vaccine types available, the vaccination rates remain dismal, thereby leading to high incidence of the disease. In this report, we discuss a case of an unvaccinated patient with end-stage renal disease who contracted the influenza virus with fatal consequences. This report discusses multiple factors that allowed for a highly preventable disease to cause this negative outcome and provides suggestions to prevent such outcomes in the future.

Asymptomatic Cecal Perforation in a Renal Transplant Recipient After Sodium Polystyrene Sulfonate Administration.

Sodium polystyrene sulfonate (SPS) is a medication commonly used for the treatment of hyperkalemia. There have been many cases of colonic necrosis and perforation associated with administration of SPS. There are very few such cases reported in renal transplant patients. We present a case of renal transplant recipient who developed cecal perforation after a single oral dose of SPS. She had no signs or symptoms suggestive of intestinal perforation and was incidentally diagnosed with it on abdominal imaging performed to find cause of acute blood loss anemia. This case underlines the importance of recognizing this severe and potentially life-threatening complication associated with SPS. The clinicians should also consider renal/solid organ transplant and immunosuppression as potential risk factors.

Ileal Neobladder With Mucous Plugs as a Cause of Obstructive Acute Kidney Injury Requiring Emergent Hemodialysis.

Ileal neobladder is the preferred technique in the management of urinary diversion postradical cystectomy for bladder malignancy. The common complications associated with this procedure are atrophied kidney, chronic pyelonephritis, decreased renal function, ureteroileal or urethral anastomotic site stricture, urinary tract stones, incontinence, and hyperchloremic metabolic acidosis. Mucous plugs are also seen in 2%-3% patients. We present a rare presentation of a patient who required hemodialysis for severe hyperkalemia and acute kidney injury caused by mucous plugging of ileal neobladder.

A Case of Gestational Thyrotoxicosis Associated with Wernicke's Encephalopathy.

OBJECTIVE: To present a case of gestational thyrotoxicosis and hyperemesis gravidarum associated with Wernicke's encephalopathy. METHODS: We present a detailed case report with the clinical, imaging, and laboratory findings of the patient and review the pertinent literature. RESULTS: A 36-year-old woman at 14 weeks of gestation was admitted to the hospital for management of severe hyperemesis gravidarum (HG). While hospitalized, she developed low-grade fever, tachycardia, hypotension, and altered mentation. Laboratory tests were diagnostic of hyperthyroidism. Physical examination revealed a confused, lethargic woman with a normal-size thyroid and pendular nystagmus in primary and lateral gaze. She was treated empirically for thyroid storm with methimazole and other measures. A brain magnetic resonance imaging (MRI) study done later showed hyperintense abnormal signals in bilateral thalamic regions, consistent with Wernicke's encephalopathy (WE). She was immediately started on intravenous thiamine and her mental status improved considerably within 3 to 4 days. Within 2 weeks, the patient's thyroid-function tests normalized and methimazole was discontinued. A repeat brain MRI 6 months later showed marked reduction of signal intensity in both thalamic regions. CONCLUSION: This case demonstrates that gestational thyrotoxicosis in a patient with HG can precipitate acute WE, which may mimic thyroid storm and thus delay appropriate management of this neurologic disorder. We conclude that prophylactic thiamine administration may be considered before caloric replacement in patients who present with HG and acute neurologic dysfunction.

TRPM8 affects relative "cooling and heating" of subcellular organelles in microglia in a context-dependent manner.

Thermoregulation and thermal homeostasis at the cellular and subcellular organelle level are poorly understood events. In this work, we used BV2, a microglial cell line, and a series of thermo-sensitive subcellular organelle-specific probes to analyze the relative changes in the spatio-temporal temperatures of different subcellular organelles, both qualitatively and quantitatively. These methodologies allowed us to understand the thermal relationship of different subcellular organelles also. We modulated BV2 cells by pharmacological application of activator or inhibitor of TRPM8 ion channel (a cold-sensitive ion channel) and/or by treating the cells with LPS, a molecule that induces pathogen-associated molecular patterns (PAMPs) signaling. We demonstrate that the temperatures of individual organelles remain variable within a physiological range, yet vary in different conditions. We also demonstrate that treating BV2 cells by TRPM8 modulators and/or LPS alters the organelle temperatures in a specific and context-dependent manner. We show that TRPM8 modulation and/or LPS can alter the relationship of mitochondrial membrane potential to mitochondrial temperature. Our work suggests that mitochondrial temperature positively influences ER temperature and negatively influences Golgi temperature. Golgi temperature positively influences membrane temperature. This understanding of thermal relationships may be crucial for dissecting cellular structures, function, and stress signaling and may be relevant for different diseases.

Evaluation of potential toxic heavy metal contamination in soil, fly ash, vegetables and grain crops along with associated ecological and health risk assessment of nearby inhabitants of a thermal power station in Jharkhand (India).

The present study aimed to evaluate the potential toxic heavy metal (PTHM) concentrations and associated ecological and health risk of nearby inhabitants (child and adult populations) of the Bokaro thermal power station (BTPS), Jharkhand, India. The fly ash containing PTHMs is released from the thermal power plant and contaminates the soil of the nearby agricultural area, roadside area and residential area. Furthermore, PTHMs cause ecological risk as well as carcinogenic health effects in adults. Inhabitants are exposed to PTHMs through exposure pathways (for instance, direct ingestion, dermal contact and air inhalation), and PTHMs were examined in this study by calculating the estimated daily intake (EDI). The contamination factor (Cf) of Cd exceeded the threshold value throughout the study area, whereas the Cf of Hg was observed higher only in roadside soil (RSS). The geoaccumulation index (Igeo) of Cd was higher in the top soil of agricultural soil (AS) (7.39) and RSS (9.38). The level of PTHMs was monitored slightly higher in the topsoil of RSS. The ecological risk index (Eri) was detected to be the highest in RSS (1628.9). The permissible limit of Cd (0.05 mg kg-1) and Pb (0.1 mg kg-1) for all sampled vegetables and grain crops was surpassed. The transfer factor (TF) of the studied vegetables and grain crops was in the order of Cd > Cr > Pb > Hg > As. The results of the present study concluded that the hazard quotient (HQ) values for all PTHMs analysed in soil throughout the study area were < 1, which indicates that the child population was within the safe limit. However, the adult population was at a high risk of non-carcinogenic health effects due to increased permissible limits of Cd, Pb and Cr in vegetables and grain crops whereas the target carcinogenic risk (TCR) of Pb and Cr was higher and indicated that there may be a health risk of cancer in adults.

SOD-GIF-FIT module controls plant organ size and iron uptake.

Plant organ growth is controlled by various internal and external cues. However, the underlying molecular mechanisms that coordinate plant organ growth and nutrient homeostasis remain largely unknown. Recently, Zheng et al. identified the key regulators SOD7 (suppressor of da1-1) and GRF-INTERACTING FACTOR1 (GIF1) that control organ size and iron uptake in arabidopsis (Arabidopsis thaliana).

Autonomic Correlates of Letter Cancelation Task: What the Attention Load May Evoke?

OBJECTIVE: Attention can be assessed through Letter cancelation tasks (LCT) that employ visuospatial selection and appropriate motor responses. We examined the performance in the LCT with increasing attention load, and determined the related autonomic changes. METHODS: Autonomic parameters were estimated in healthy males at baseline and during three different cognitive load conditions using the LCT. RESULTS: Results revealed a statistically significant difference (n = 30) in the percent accuracy (χ2(2) = 15.2, p < .001) and percent omission (χ2(2) = 13.3, p = 0.001) with the increasing challenge in the LCT. The vagally-mediated measures of heart rate variability were significantly decreased with the commencement of the task revealing a parasympathetic withdrawal. The respiratory sinus arrythmia was decreased, and the photoplethysmography amplitude was significantly reduced (χ2(3) = 14.2, p = 0.003) as the attention demand increased. CONCLUSION: The performance declined with the increasing attention load. LCT evokes autonomic perturbations though overall autonomic variability does not change remarkably.