Role of Heat Shock Proteins in Improving Heat Stress Tolerance in Crop Plants

High temperature response (HTR) or heat stress response (HSR) is a highly conserved phenomenon, which involves complex networks among different crop species. Heat stress usually results in protein dysfunction by improper folding of its linear amino acid chains to non-native proteins. This leads to unfavourable interactions and subsequent protein aggregation. To tackle this, plants have developed molecular chaperone machinery to maintain high quality proteins in the cell. This is governed by increasing the level of pre-existing molecular chaperones and by expressing additional chaperones through signalling mechanism. Dissecting the molecular mechanism by which plants counter heat stress and identification of important molecules involved are of high priority. This could help in the development of plants with improved heat stress tolerance through advanced genomics and genetic engineering approaches. Owing to this reason molecular chaperones/Heat shock proteins (Hsps) are considered as potential candidates to address the issue of heat stress. In this chapter, recent progress on systematic analyses of heat shock proteins, their classification and role in plant response to heat stress along with an overview of genomic and transgenic approaches to overcome the issue, are summarized

Molecular characterization and expression analysis of pearl millet plasma membrane proteolipid 3 (Pmp3) genes in response to abiotic stress conditions

Plasma membrane proteolipid 3 (Pmp3) is a gene family involved in abiotic stress response and cellular protection. Here we report cloning of two genes PgPmp3-1 and PgPmp3-2 from Pennisetum glaucum, and characterization with respect to their functions and responsiveness to various abiotic stresses. Both PgPmp3-1 and PgPmp3-2 genes are 171 bp long and encode for 56 amino acid long peptides. PgPmp3 sequences share 70–99% sequence identity with their homologs. Protein secondary structure prediction revealed membrane-spanning regions containing a membrane potential modulator domain in both PgPmp3 proteins. In silico network analyses revealed Pmp3 co-expression and association with proteins conferring abiotic stress tolerance in plants. Expression profiles of PgPmp3-1 and PgPmp3-2 revealed their up-regulation in P. glaucum under cold and salt stresses, but showed reduced expression in response to heat stress. These findings provide insight into the role of P. glaucum Pmp3 in abiotic stress amelioration

Salt-tolerant genes from halophytes are potential key players of salt tolerance in glycophytes

Crop productivity strongly depends on several biotic and abiotic factors. Salinity is one of the most important abiotic factors, besides drought, extreme temperatures, light and metal stress. The enhanced burden of secondary salinization induced through anthropogenic activities increases pressure on glycophytic crop plants. The recent isolation and characterization of salt tolerance genes encoding signaling components from halophytes, which naturally grow in high salinity, has provided tools for the development of transgenic crop plants with improved salt tolerance and economically beneficial traits. In addition understanding of the differences between glycophytes and halophytes with respect to levels of salinity tolerance is also one of the prerequisite to achieve this goal. Based on the recent developments in mechanisms of salt tolerance in halophytes, we will explore the potential of introducing salt tolerance by choosing the available genes from both dicotyledonous and monocotyledonous halophytes, including the salt overly sensitive system (SOS)-related cation/proton antiporters of plasma (NHX/SOS1) and vacuolar membranes (NHX), energy-related pumps, such as plasma membrane and vacuolar H+ adenosine triphosphatase (PM& V-H+ATPase), vacuolar H+ pyrophosphatases (V-H+PPase) and potassium transporter genes. Various halophyte genes responsible for other processes, such as crosstalk signaling, osmotic solutes production and reactive oxygen species (ROS) suppression, which also enhance salt tolerance will be described. In addition, the transgenic overexpression of halophytic genes in crops (rice, peanut, finger millet, soybean, tomato, alfalfa, jatropha, etc.) will be discussed as a successful mechanism for the induction of salt tolerance. Moreover, the advances in genetic engineering technology for the production of genetically modified crops to achieve the improved salinity tolerance under field conditions will also be discussed

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Genomic-based-breeding tools for tropical maize improvement

Maize has traditionally been the main staple diet in the Southern Asia and Sub-Saharan Africa and widely grown by millions of resource poor small scale farmers. Approximately, 35.4 million hectares are sown to tropical maize, constituting around 59% of the developing worlds. Tropical maize encounters tremendous challenges besides poor agro-climatic situations with average yields recorded <3 tones/hectare that is far less than the average of developed countries. On the contrary to poor yields, the demand for maize as food, feed, and fuel is continuously increasing in these regions. Heterosis breeding introduced in early 90 s improved maize yields significantly, but genetic gains is still a mirage, particularly for crop growing under marginal environments. Application of molecular markers has accelerated the pace of maize breeding to some extent. The availability of array of sequencing and genotyping technologies offers unrivalled service to improve precision in maize-breeding programs through modern approaches such as genomic selection, genome-wide association studies, bulk segregant analysis-based sequencing approaches, etc. Superior alleles underlying complex traits can easily be identified and introgressed efficiently using these sequence-based approaches. Integration of genomic tools and techniques with advanced genetic resources such as nested association mapping and backcross nested association mapping could certainly address the genetic issues in maize improvement programs in developing countries. Huge diversity in tropical maize and its inherent capacity for doubled haploid technology offers advantage to apply the next generation genomic tools for accelerating production in marginal environments of tropical and subtropical world. Precision in phenotyping is the key for success of any molecular-breeding approach. This article reviews genomic technologies and their application to improve agronomic traits in tropical maize breeding has been reviewed in detail

Elastic properties of Na(2)O-B(2)O(3)-V(2)O(5) glasses

This paper describes the sound velocity and the elastic properties of Na(2)O-B(2)O(3)-V(2)O(5) glasses over a wide range of composition. Sound velocities (transverse and longitudinal) have been measured using a pulse echo superposition method at a frequency of 10 MHz. The elastic moduli (L, G, K and E), Poisson's ratio (sigma) and Debye temperature (theta(D)) exhibit composition dependent trends. The variation of these parameters has been explained using a structural motifs present and the dimensionality of the glass network. (C) 2008 Elsevier B.V. All rights reserved

Infrared and MAS NMR studies of potassium borovanadate glasses

Glass system of the composition xK(2)O-(90 - x)B2O3-10V(2)O(5) (where x = 10, 20, 30, 40, and 50 mol%) have been prepared by melt quenching technique and characterized for their densities, and glass transition temperatures. The structure of the glasses has been investigated using infrared and magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy. The structural changes occur due to the addition of modifier oxide. Modification is based on the Sanderson's elect ronegativity principle, leading to the formation of [B2V2O9](2-) (type I and type II), [BO4/2](-) and [BO2/2O](-). This is followed by a structural rearrangement that is the ratio of B-4/B-4 + B-3 = N-4 increases up to 40 K2O mol%, further increase in modifier oxide concentration levels off N-4. The nature of speciation is examined using structural model. The variation of different properties is consistent with this model. (C) 2008 Elsevier B.V. All rights reserved

Ledipasvir/sofosbuvir induced nephrotic syndrome: A challenging case of Hepatitis C management

ABSTRACT: Hepatitis C virus (HCV) is associated with various glomerulopathies and nephrotic syndrome. However nephrotic syndrome following treatment is rare. Ledipasvir/sofosbuvir (L/S) has recently come into favor in treating HCV due to its relatively mild side effects compared to the more traditional interferon therapy. To the best of our knowledge, there are no reported cases of nephrotic syndrome following treatment with L/S. We present a case of nephrotic syndrome suspected secondary to L/S in a patient with chronic kidney disease. Increased vigilance when assessing therapeutic options in HCV patients with renal comorbidities can improve patient outcomes. A 63 year-old male patient presented to the hospital with shortness of breath, and a two-week history of bilateral lower extremity edema. Past medical history was significant for liver cirrhosis secondary to Hepatitis C genotype Ia, hepatocellular carcinoma status post liver transplantation 6 months prior to admission and Stage 3b chronic kidney disease with baseline creatinine (Cr) approximately 1.5 mg/dl. Medications included L/S for HCV and tacrolimus and prednisone for post-transplant treatment. Patient’s vitals were stable and physical exam was remarkable for facial swelling, mainly on the eyelids, decreased breath sounds bilaterally, distended abdomen with a fluid wave, and 2-3+ pitting edema up to the knees on lower extremities bilaterally. Laboratory work-up was remarkable for low albumin of 3.0 g/dl, and total protein of 5.6 g/ dl. Creatinine of 1.8 mg/dl was elevated from patient’s baseline. HCV viral load was undetectable and electrolytes, transaminases and the complete blood count were within normal limits. Subsequently, urine protein to creatinine ratio was measured because of generalized swelling and hypoproteinemia, which was found to be significantly high at 8.80, compared to 0.04 one year prior. 24-hour total urine protein was found to be 2065 mg/day. Renal ultrasonography showed no hydronephrosis and was otherwise unremarkable. Renal biopsy however, revealed changes suggestive of membranoproliferative glomerulonephritis (MPGN] most likely secondary to HCV. No immune complexes, lambda/kappa light chains, or cryogloblin were appreciated. Nephrotoxic agents such as diuretics and corticosteroids were held. Tacrolimus trough was appropriate to dose level and was continued along with L/S. As admission progressed the patient’s creatinine continued to get worse and rose up to 4.3 mg/dl with persistent proteinuria. With tacrolimus trough levels within normal limits and given L/S was the most recently initiated drug, L/S was thought to be the culprit and was thus held. The renal function began to improve gradually, and the patient was discharged in stable condition with close follow up. Follow up one month later found creatinine and renal function return to baseline and proteinuria resolved. Our case shows that Ledipasvir/sofosbuvir may possibly be related to nephrotic syndrome in HCV patients. Although further studies are needed to prove the causality our case seeks to raise clinical suspicion and increase vigilance when assessing therapeutic options in HCV patients with renal comorbidities such as chronic kidney disease

Infrared and MAS NMR studies of potassium borovanadate glasses

Glass system of the composition $xK_2O-(90-x)B_2O_3-10V_2O_5$ (where x = 10, 20, 30, 40, and 50 mol%) have been prepared by melt quenching technique and characterized for their densities, and glass transition temperatures. The structure of the glasses has been investigated using infrared and magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy. The structural changes occur due to the addition of modifier oxide. Modification is based on the Sanderson’s electronegativity principle, leading to the formation of $[B_2V_2O_9]^{2-}$ (type I and type II), $[BO_{4/2}]^-$ and $[BO_{2/2}O]^-$. This is followed by a structural rearrangement that is the ratio of $B_4/B_4 + B_3 = N_4$ increases up to 40 $K_2O$ mol%, further increase in modifier oxide concentration levels off $N_4$. The nature of speciation is examined using structural model. The variation of different properties is consistent with this model