Spatial and temporal expression analysis of D-myo-inositol 3-phosphate synthase (MIPS) gene family in Glycine max

Phytic acid, the principal storage form of phosphorus in plant seeds accounts for up to 60 to 80% of the total seed phosphorus content in soybean. Its accumulation increases linearly throughout seed  development and it strongly chelates essential mineral cations and charged proteins decreasing their bioavailability. D-Myo-inositol 3-phosphate synthase (MIPS; EC 5.5.1.4), the evolutionarily conserved enzyme in plants, catalyzes the first and the rate limiting step in phytic acid biosynthetic pathway. Aiming at controlling the level of phytate, we monitored the differential expression profile of four, previously reported, members of the MIPS gene family in developing seeds and vegetative tissues of soybean by quantitative real-time PCR (qRT-PCR). Transcript levels were measured relative to the endogenous reference gene eEF-1á (eukaryotic elongation factor 1-alpha) using SYBER-Green. The qRT-PCR data analysis indicated that the expression of the four highly conserved MIPS genes is both temporally and spatially regulated, information much needed for reverse genetic applications. MIPS1 exhibited high transcript levels in the early developing cotyledons with the levels peaking at around 4 to 6 mm seed size stage. Despite of high level of nucleotide sequence conservation amongst the MIPS gene family members, MIPS2, MIPS3 and MIPS4 were poorly expressed in developing seed tissues, although their transcript levels were relatively high in the other organ tissues. MIPS1 was however moderately expressed in seedlings where MIPS2 showed relatively higher expression levels. Among the four isoforms, MIPS4 had the highest transcript levels in the leaf tissue. The data was clearly indicative of the fact that the four isoforms had diverged regulatory elements resulting in their differential expression. Of the four members of the MIPS gene family, MIPS1 is thus the major isoform that had high expression in the developing seed tissues and can be targeted using the dsRNA induced sequence specific RNA degradation mechanism for reduction of phytate levels without affecting the critical aspects of inositol metabolism in other tissues of the plant.Key words: Soybean, MIPS isoforms, differential expression, endogenous reference gene, qRT-PCR

Enhanced Lymphatic Uptake of Leflunomide Loaded Nanolipid Carrier via Chylomicron Formation for the Treatment of Rheumatoid Arthritis

Purpose: The current study aims the lymphatic delivery of leflunomide loaded nanostructured lipid carriers (LNLC) for the treatment of rheumatoid arthritis, mainly focussed to enhance the lymphatic delivery via chylomicron formation, improved bioavailability and reduced systemic toxicity. Methods: Melt emulsification ultra-sonication method was used to formulate the nanostructured lipid carrier (NLC) containing leflunomide. Four batches were prepared by using various concentration of surfactants (tween 80 and poloxmer 188) and lipid mixtures (stearic acid and oleic acid). All the formulations were studied for various physiochemical properties Results: The formulation with increased concentration of lipid and surfactants showed highest entrapment efficiency (93.96 ± 0.47%) and better drug release (90.35%) at the end of 48 hrs. In vivo tests were carried out to determine the antiarthritic potential of the formulation in Sprague-dawley rats for a duration of 30d. The effect was evaluated by measuring the reduction in knee thickness. LNLC showed a marked reduction in inflammation compared to standard drug. Intestinal lymphatic uptake studies of LNLC were performed by intraduodenal administration and compared with leflunomide drug solution. The mesenteric lymph node was analysed by HPLC method and the concentration of drug was estimated. It showed that LNLC having highest uptake (40.34μg/ml) when compared with leflunomide drug solution (10.04μg/ml). Radiographic analysis and histopathological studies showed the formation of healthy cartilage after treatment period. Conclusion: The results suggested that LNLC has the potential to reduce the systemic toxicities associated with conventional therapy along with improved efficacy in the treatment of rheumatoid arthritis

Artificial Intelligence/Operations Research Workshop 2 Report Out

This workshop Report Out focuses on the foundational elements of trustworthy AI and OR technology, and how to ensure all AI and OR systems implement these elements in their system designs. Four sessions on various topics within Trustworthy AI were held, these being Fairness, Explainable AI/Causality, Robustness/Privacy, and Human Alignment and Human-Computer Interaction. Following discussions of each of these topics, workshop participants also brainstormed challenge problems which require the collaboration of AI and OR researchers and will result in the integration of basic techniques from both fields to eventually benefit societal needs

Developing Tailor-Made Microbial Consortium for Effluent Remediation

The work describes a biofilm-based soluble sulphate reduction system, which can treat up to 1600 ppm of soluble sulphate within 3.5 hours of incubation to discharge level under ambient condition using a well-characterized sulphate-reducing bacterial (SRB) consortium. This system ensures the treatment of 1509 litres of sulphate solution in 24 hours using a 220-litre bioreactor. Performance of the system during series operation was compromised, indicating the presence of inhibitor in solution at a toxic level. A single unit bioreactor would be the ideal configuration for this consortium. Modified designs of bioreactors were tested for optimization of the process using response surface methodology (RSM), where the system could function optimally at an initial sulphate concentration of 1250 ppm with a flow rate of 1.8 litre/hour. The time course of sulphate reduction yielded a parabolic profile (with coefficient of determination r 2 = 0.99 and p value < 0.05). The rate of sulphate reduction was found to be independent of seasonal variation as well as the specific design characteristic

The Role of Major Phenolics in Apple to Total Antioxidant Capacity

The naturally occurring phenolic compounds have received major attention in recent years as huge amounts of phenolic compounds can be extracted from fruits, vegetables and beverages that have substantial health benefits. From a physiological and metabolic aspect, phenolic compounds are vital in defence responses, such as anti-ageing, anti-inflammatory, anti-oxidant and anti-proliferative, anti-bacterial, anti-hyperlipidemic, anti-cancer, anti-diabetic, neuroprotective, cardioprotective activities. Among the fruits having a higher content of phenolic compounds, the apple (Malus Domestica) is the most widely consumed fruit in the world. Apples have a high nutritional value as it is a rich source of ascorbic acid, polyphenols and pectin. Apple peel forms a small percentage (6–8%) of the total fruit weight and contains the highest content of phenolic compounds, particularly chlorogenic acid. There are five major groups of polyphenolic compounds found in apples namely flavanols (Catechin, Epicatechin and Pyrocyanidins), phenolic compounds, phenolic acids (mainly Chlorogenic acids), dihydrochalcones (Phloretin glycosides), flavonols (Quercetin glycosides) and anthocyanins (Cyanidin). This chapter reviews the chemical properties, mode of action, types, extraction of phenolics in apples and the contribution and role of major phenolics in apples to the total antioxidant capacity

Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy:a multicentre double-blind pilot randomised controlled trial

Objective: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE). Design: Double-blind pilot randomised controlled trial.Setting: Eight neonatal units in South Asia. Patients: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023. Interventions: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age. Main outcomes and measures: Feasibility of randomisation, drug administration and assessment of brain injury using MRI. Results: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group. Conclusions: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings. Trial registration number: NCT05395195

Pharmacometabolomics of Response to Sertraline and to Placebo in Major Depressive Disorder - Possible Role for Methoxyindole Pathway

10.1371/journal.pone.0068283PLoS ONE87-POLN