High-Level Expression of the Brugia malayi Protein Kinase, Bm-MPK 1, in Insect SF9 Cells

Lymphatic Filariasis (elephantiasis) is a neglected tropical disease caused by the filarial nematodes Brugia malayi (B. malayi), Brugia timori, and Wuchererici Bancrofti (1,8). These parasites are present in over 83 counties in the tropics and sub-tropics where more than 1.4 billion people are at risk of infection and 130 million people are presently infected (1,7). Previous work from our lab has led to the identification and expression of a B. malayi stress-activated protein kinase, Bm-MPKl (a human p38/C. elegans PMK-1 ortholog). Bm-MPKl plays an important role in the parasites’ protection against oxidative stress (1), and as such is a potential therapeutic drug target for the treatment of Lymphatic Filariasis. Bm-MPKl was successfully expressed in mammalian HEK-293 F cells yielding levels suitable for characterization of the enzyme. However, these cells did not produce adequate levels of recombinant protein for crystallography and high throughput screening purposes. In order to produce high levels of recombinant Bm- MPKl, I have established a novel SF9 cell/Baculovirus expression system. A synthetic Bm-MPKl was successfully subcloned into a pFASTBAC plasmid, which was then transposed into DHlOBac cells to generate a Bm-MPKl/pFASTBAC-based baculovirus. Using this system, I have demonstrated that recombinant Bm-MPKl protein kinase is highly expressed in infected SF9 insect cells. Similar to mammalian cell expression, I demonstrated that Bm-MPKl can be activated in SF9 infected cells by treatment with sodium arsenate. An excellent yield of recombinant Bm-MPKl was obtained with approximately 3.25 mg of protein recovered from a 100 mL culture

Metal coordinated macrocyclic complexes in different chemical transformations

Macrocyclic ligand chemistry is seen by a growing number of scientists as a tool for designing new molecules with inherently selective properties. Metal coordinated macrocyclic rings are featured with exceptionally stable π-conjugated cyclic systems containing the metal ion in the central cavity. The cyclic tetra dentate framework of the four central nitrogen atoms makes these macrocyclic rings system unique chelating agents, in addition, these conjugated double bonds impart a vital effect in electrons transportation. Because of inimitable characteristics, these metal coordinated macrocyclic compounds have been effectively applied as catalysts in various important organic transformations. Hence, this review portrays the overview of metal coordinated macrocyclic molecules, classifications, and their catalytic application in redox reactions. This comprehensive and up-to-date review is particularly aligned toward the catalytic applications of four types of metal-coordinated macrocyclic rings, i.e., porphyrin, porphyrazine, corrole, and corrolazines, in different organic transformations. The different synthetic approaches for the preparation of metal coordinated macrocyclic rings and their UV spectrums are also outlined in this review

Development and optimization of NIRS prediction models for simultaneous multi-trait assessment in diverse cowpea germplasm

Cowpea (Vigna unguiculata (L.) Walp.) is one such legume that can facilitate achieving sustainable nutrition and climate change goals. Assessing nutritional traits conventionally can be laborious and time-consuming. NIRS is a technique used to rapidly determine biochemical parameters for large germplasm. NIRS prediction models were developed to assess protein, starch, TDF, phenols, and phytic acid based on MPLS regression. Higher RSQexternal values such as 0.903, 0.997, 0.901, 0.706, and 0.955 were obtained for protein, starch, TDF, phenols, and phytic acid respectively. Models for all the traits displayed RPD values of >2.5 except phenols and low SEP indicating the excellent prediction of models. For all the traits worked, p-value ≥ 0.05 implied the accuracy and reliability score >0.8 (except phenol) ensured the applicability of the models. These prediction models will facilitate high throughput screening of large cowpea germplasm in a non-destructive way and the selection of desirable chemotypes in any genetic background with huge application in cowpea crop improvement programs across the world

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

A Long-Range Internet of Things-Based Advanced Vehicle Pollution Monitoring System with Node Authentication and Blockchain

According to United Nations (UN) 2030 agenda, the pollution detection system needs to be improved for the establishment of fresh air to obtain healthy life of living things. There are many reasons for the pollution and one of the reasons for pollution is from the emissions of the vehicles. Currently digital technologies such as the Internet of Things and Long-Range are showing significant impact on establishment of smart infrastructure for achieving the sustainability. Based on this motivation, this study implemented a sensor node and gateway-based Internet of Things architecture to monitor the air quality index value from any location through Long-Range communication, and Internet connectivity. To realize the proposed system, a customization of hardware is carried out and implemented the customized hardware i.e., sensor node and gateway in real-time. The sensor node is powered with node mapping to minimize the data redundancy. In this study, the evaluation metrics such as bit rate, receiver sensitivity, and time on air are evaluated by spreading factor (SF), code rate (CR), bandwidth, number of packets, payload size, preamble, and noise figure. The real-time sensor values are logged on the cloud server through sensor node and gateway. The sensor values recorded in the cloud server is compared with optimal values and concluded that the PM10, PM2.5 are high in the air and remaining values of NO2, O3, CO are optimal in the air. Along with this an architecture is proposed for interfacing the hardware with blockchain network through cloud server and API for node authentication

Ab-initio study of free standing TiO2 clusters: Stability and magnetism

We report the structural behavior of nanoscale Titanium Dioxide (TiO2) clusters as well as their magnetic properties by varying the cluster size with the help of ground state geometries. The clusters of atomic scale rutile (TiO2)n, where n = 1-11, have been considered and geometrically stabilized through the Density Functional Theory as implemented in Vienna ab-initio Simulation Package. It is being observed that as the size of cluster increases from n = 2 to 11, the total energy decreases. The results of formation energy reveal the fact that as the cluster grows, it moves towards the stability and it is observed that n = 11 is the most stable structure. The stabilized clusters are different in geometries and co-ordination numbers. Finally, all the clusters have been investigated with self-consistent treatment of spin orbit coupling for magnetism studies. The magnetic properties of free clusters depict oscillatory behavior for magnetic moment with respect to the cluster size

Successful management of patients with co-existent autoimmune hepatitis and graves\u27 disease.

Introduction Graves\u27 disease is an autoimmune disorder characterized by autoantibodies against the TSH receptor. Hyperthyroidism from Graves\u27 disease is a high turnover state which can result in elevated liver enzymes. Autoimmune hepatitis (AIH) is a chronic liver disease that presents with elevated liver enzymes, gammaglobulinemia, and unique histological features. Here, we report 4 cases of women diagnosed with AIH and Graves\u27 disease. Clinical cases Case 1 A 15 year old female was diagnosed with Graves\u27 disease after workup revealed low TSH, elevated thyroid hormones, and elevated TSI. At baseline, she had elevated liver enzymes attributed to hyperthyroidism. She underwent RAI ablation. Due to persistently elevated liver enzymes, liver biopsy was performed revealing portal fibrosis and interface hepatitis consistent with AIH. Steroid therapy was initiated and she responded well. Case 2 An 11 year old female was diagnosed with Graves\u27 disease after lab tests revealed low TSH with elevated T3 and T4. She failed anti-thyroid drug treatment and was eventually treated with RAI. Five years later, she developed AIH. This progressed despite treatment, and she underwent a successful liver transplant. Case 3 A 39 year old female presented to the hospital with malaise. She was diagnosed with Graves\u27 disease and AIH. She was started on prednisone and anti-thyroid drugs. Subsequently, she was treated with RAI and she went into remission with AIH as well. She had a recurrence of the latter and required a liver transplant. Case 4 A 47 year old female presented with jaundice. Workup revealed elevated liver enzymes with positive ANA and ASMA. Liver biopsy revealed hepatic necrosis and bridging fibrosis confirming AIH. Immunosuppression was initiated with good response. She was later diagnosed with Graves\u27 and was started on anti-thyroid drug therapy. She was maintained on long term methimazole and prednisone. Discussion As elevated liver enzymes are commonly seen in patients with Graves\u27 disease, a high index of suspicion is required to diagnose concomitant AIH since Graves\u27 disease is rarely associated with AIH. We described 4 patients with concomitant thyroid and liver disease. In some cases, the diagnosis of AIH was delayed as the initial liver enzyme abnormalities were attributed to hyperthyroidism. Physicians may be hesitant to use anti-thyroid drugs given their hepatic side effect profile. However, anti-thyroid drug therapy can be safely used even in the presence of advanced liver disease, and may prove beneficial. In 2 of our patients, liver enzymes improved after hyperthyroidism resolved. In patients with co-existent AIH and Graves\u27 disease, RAI ablation is the preferred modality for treatment. AIH treated with immunosuppression may also treat Graves\u27 disease with improvement of both liver and thyroid function

Successful management of patients with co-existent autoimmune hepatitis and graves\u27 disease.

Introduction Graves\u27 disease is an autoimmune disorder characterized by autoantibodies against the TSH receptor. Hyperthyroidism from Graves\u27 disease is a high turnover state which can result in elevated liver enzymes. Autoimmune hepatitis (AIH) is a chronic liver disease that presents with elevated liver enzymes, gammaglobulinemia, and unique histological features. Here, we report 4 cases of women diagnosed with AIH and Graves\u27 disease. Clinical cases Case 1 A 15 year old female was diagnosed with Graves\u27 disease after workup revealed low TSH, elevated thyroid hormones, and elevated TSI. At baseline, she had elevated liver enzymes attributed to hyperthyroidism. She underwent RAI ablation. Due to persistently elevated liver enzymes, liver biopsy was performed revealing portal fibrosis and interface hepatitis consistent with AIH. Steroid therapy was initiated and she responded well. Case 2 An 11 year old female was diagnosed with Graves\u27 disease after lab tests revealed low TSH with elevated T3 and T4. She failed anti-thyroid drug treatment and was eventually treated with RAI. Five years later, she developed AIH. This progressed despite treatment, and she underwent a successful liver transplant. Case 3 A 39 year old female presented to the hospital with malaise. She was diagnosed with Graves\u27 disease and AIH. She was started on prednisone and anti-thyroid drugs. Subsequently, she was treated with RAI and she went into remission with AIH as well. She had a recurrence of the latter and required a liver transplant. Case 4 A 47 year old female presented with jaundice. Workup revealed elevated liver enzymes with positive ANA and ASMA. Liver biopsy revealed hepatic necrosis and bridging fibrosis confirming AIH. Immunosuppression was initiated with good response. She was later diagnosed with Graves\u27 and was started on anti-thyroid drug therapy. She was maintained on long term methimazole and prednisone. Discussion As elevated liver enzymes are commonly seen in patients with Graves\u27 disease, a high index of suspicion is required to diagnose concomitant AIH since Graves\u27 disease is rarely associated with AIH. We described 4 patients with concomitant thyroid and liver disease. In some cases, the diagnosis of AIH was delayed as the initial liver enzyme abnormalities were attributed to hyperthyroidism. Physicians may be hesitant to use anti-thyroid drugs given their hepatic side effect profile. However, anti-thyroid drug therapy can be safely used even in the presence of advanced liver disease, and may prove beneficial. In 2 of our patients, liver enzymes improved after hyperthyroidism resolved. In patients with co-existent AIH and Graves\u27 disease, RAI ablation is the preferred modality for treatment. AIH treated with immunosuppression may also treat Graves\u27 disease with improvement of both liver and thyroid function

Successful Management of Patients with Co-existent Graves\u27 Disease and Autoimmune Hepatitis

Graves\u27 disease may lead to hepatic dysfunction. This is due to the direct effect of increased circulation of thyroid hormones. Graves\u27 disease is associated with other autoimmune diseases, including autoimmune hepatitis. We report four cases of a rare occurrence of both Graves\u27 disease and autoimmune hepatitis. Two female patients underwent radioactive iodine ablation for Graves\u27 disease. Both patients were diagnosed with autoimmune hepatitis with liver biopsy after liver enzymes worsened despite stable thyroid function. Both patients received steroid immunosuppression therapy for autoimmune hepatitis. The first patient improved with return of thyroid function and liver enzymes to normal whereas the second patient\u27s liver disease progressed despite treatment and she eventually required liver transplant. A female patient with concomitantly diagnosed Graves\u27 disease and autoimmune hepatitis was initially treated with steroids and anti-thyroid medication. She then underwent radioactive iodine ablation but ultimately required liver transplant. Another female patient received treatment with immunosuppression and anti-thyroid therapy. She eventually underwent radioactive iodine ablation with normalization of thyroid function and liver profile. This case series illustrates the diagnostic challenge to determine the cause of elevated liver enzymes in patients presenting with both Graves\u27 disease and autoimmune hepatitis. A brief review of the literature on its clinical presentation and diagnosis is discussed