The interplay between mitochondria and store-operated Ca2+ entry: Emerging insights into cardiac diseases

Store-operated Ca²⁺ entry (SOCE) machinery, including Orai channels, TRPCs, and STIM1, is key to cellular calcium homeostasis. The following characteristics of mitochondria are involved in the physiological and pathological regulation of cells: mitochondria mediate calcium uptake through calcium uniporters; mitochondria are regulated by mitochondrial dynamic related proteins (OPA1, MFN1/2, and DRP1) and form mitochondrial networks through continuous fission and fusion; mitochondria supply NADH to the electron transport chain through the Krebs cycle to produce ATP; under stress, mitochondria will produce excessive reactive oxygen species to regulate mitochondria-endoplasmic reticulum interactions and the related signalling pathways. Both SOCE and mitochondria play critical roles in mediating cardiac hypertrophy, diabetic cardiomyopathy, and cardiac ischaemia-reperfusion injury. All the mitochondrial characteristics mentioned above are determinants of SOCE activity, and vice versa. Ca²⁺ signalling dictates the reciprocal regulation between mitochondria and SOCE under the specific pathological conditions of cardiomyocytes. The coupling of mitochondria and SOCE is essential for various pathophysiological processes in the heart. Herein, we review the research focussing on the reciprocal regulation between mitochondria and SOCE and provide potential interplay patterns in cardiac diseases.     

Direct shoot organogenesis from shoot tip explants of a highly medicinal valued tree Pterocarpus marsupium Roxb.

In Vitro Cellular & Developmental Biology - Plant - An in vitro regeneration system for propagation of a valuable medicinal tree, Pterocarpus marsupium, using shoot tip (ST) explants derived...     

Continuous degradation of maltose by enzyme entrapment technology using calcium alginate beads as a matrix

Maltase from Bacillus licheniformis KIBGE-IB4 was immobilized within calcium alginate beads using entrapment technique. Immobilized maltase showed maximum immobilization yield with 4% sodium alginate and 0.2 M calcium chloride within 90.0 min of curing time. Entrapment increases the enzyme–substrate reaction time and temperature from 5.0 to 10.0 min and 45 °C to 50 °C, respectively as compared to its free counterpart. However, pH optima remained same for maltose hydrolysis. Diffusional limitation of substrate (maltose) caused a declined in V_max of immobilized enzyme from 8411.0 to 4919.0 U ml^?1 min^?1 whereas, K_m apparently increased from 1.71 to 3.17 mM ml^?1. Immobilization also increased the stability of free maltase against a broad temperature range and enzyme retained 45% and 32% activity at 55 °C and 60 °C, respectively after 90.0 min. Immobilized enzyme also exhibited recycling efficiency more than six cycles and retained 17% of its initial activity even after 6th cycles. Immobilized enzyme showed relatively better storage stability at 4 °C and 30 °C after 60.0 days as compared to free enzyme.     

Fungal metabolites as anti-diabetic agents: emphasis on PTP1B inhibitors

Phytochemistry Reviews - In the last decade the prevalence of diabetes has escalated globally and it is estimated that the number of diabetic people will increase to 642 million by 2040. Although...     

Arabidopsis U‐box E3 ubiquitin ligase PUB11 negatively regulates drought tolerance by degrading the receptor‐like protein kinases LRR1 and KIN7

Both plant receptor‐like protein kinases (RLKs) and ubiquitin‐mediated proteolysis play crucial roles in plant responses to drought stress. However, the mechanism by which E3 ubiquitin ligases modulate RLKs is poorly understood. In this study, we showed that Arabidopsis PLANT U‐BOX PROTEIN 11 (PUB11), an E3 ubiquitin ligase, negatively regulates abscisic acid (ABA)‐mediated drought responses. PUB11 interacts with and ubiquitinates two receptor‐like protein kinases, LEUCINE RICH REPEAT PROTEIN 1 (LRR1) and KINASE 7 (KIN7), and mediates their degradation during plant responses to drought stress in vitro and in vivo. pub11 mutants were more tolerant, whereas lrr1 and kin7 mutants were more sensitive, to drought stress than the wild type. Genetic analyses show that the pub11 lrr1 kin7 triple mutant exhibited similar drought sensitivity as the lrr1 kin7 double mutant, placing PUB11 upstream of the two RLKs. Abscisic acid and drought treatment promoted the accumulation of PUB11, which likely accelerates LRR1 and KIN7 degradation. Together, our results reveal that PUB11 negatively regulates plant responses to drought stress by destabilizing the LRR1 and KIN7 RLKs.     

Early Eocene orthophragminids from the Lower Indus Basin,Pakistan, and their biostratigraphic implication

Orthophragminids are a key biostratigraphic proxy for Paleocene–Eocene sequences in western Tethys, but poorly known in eastern Tethys. The orthophragminids were previously misinterpreted as Paleocene's orbitoidiform foraminifera in the Indus Basin, Pakistan. This study focuses on detailed taxonomy and biostratigraphy of orthophragminids. Nine species/subspecies of orthophragminids are identified, including Discocyclina ranikotensis, D. archiaci bakhchisaraiensis, D. a. ex. interc. staroseliensis bakhchisaraiensis, D. dispansa hungarica, D. d. taurica, D. d. broennimanni and Orbitoclypeus schopeni ramaraoi, and two new species Discocyclina pseudoranikotensis n. sp. and Discocyclina debalensis n. sp. are described. The identified orthophragminid taxa represent the orthophragminid zones OZ2-3, corresponding to the shallow benthic zones SBZ5-7 of early Ypresian (early Eocene), which are correlated with those in western Tethys. However, we found that the first appearances of D. d. hungarica and D. d. taurica occur in the OZ3 or SBZ7 in this study instead of the OZ5 or SBZ10 as in western Tethys. The possible paleoecological setting for the occurrences of recognized species is interpreted as inner to middle shelf.     

Molecular and chemical characterization of plants regenerated from Ri-mediated hairy root cultures of Rauwolfia serpentina

Hairy root lines were induced from leaf explants of Rauwolfia serpentina known to contain high levels of reserpine (0.0882 % DW) content. Out of five high yielding hairy root lines, three (R1, R14 and R15) exhibited spontaneous regeneration of shoots after 6–8 weeks in liquid B5 medium. Excised regenerated shoots underwent robust shoot proliferation when cultured on Murashige and Skoog (MS) medium supplemented with 0.1 mg/l naphthanleneacetic acid (NAA) and 1.0 mg/l 6-benzyladenine. When shoots were transferred to a root induction medium, consisting of MS basal medium and 1.0 mg/l NAA, all rooted within 2–3 weeks. Of a total of 45 plants developed from three different hairy root lines, 30 were successfully acclimatized and transferred to the green house. Almost 90 % of these plants grown in the green house showed no observed phenotypic differences, while 10 % were stunted and grew poorly, in comparison to non-transformed plants. Phenotypic assessment of regenerated plants for plant length, number of nodes and intermodal lengths, number of leaves per node, leaf color, leaf size, number of flowering shoots, flower size, fruit size, lateral root branching and root biomass was conducted. Polymerase chain reaction and Southern blot hybridization revealed that all plants derived from hairy roots carried the Ri T_L-DNA fragment. Moreover for plants derived from transgenic hairy root line R14, presence of more than a single transgene copy number was observed, and this might have contributed to observed abnormal phenotypes. Analysis of reserpine content revealed that roots of regenerated plants had similar levels (0.0889 % DW) to those of their corresponding hairy roots.     

Differential phosphorylation regulates the shear stress-induced polar activity of Rho-specific guanine nucleotide dissociation inhibitor α

The activity of Rho-specific guanine nucleotide dissociation inhibitor α (RhoGDIα) is regulated by its own phosphorylation at different amino acid sites. These phosphorylation sites may have a crucial role in local Rho GTPases activation during cell migration. This paper is designed to explore the influence of phosphorylation on shear stress-induced spatial RhoGDIα activation. Based on the fluorescence resonance energy transfer biosensor sl-RhoGDIα, which was constructed to test the RhoGDIα activity in living cells, new RhoGDIα phosphomimetic mutation (sl-S101E/S174E, sl-Y156E, sl-S101E, sl-S174E) and phosphorylation-deficient mutation (sl-S101A/S174A, sl-Y156A, sl-S101A, sl-S174A) biosensors were designed to test their effects on RhoGDIα activation upon shear stress application in human umbilical vein endothelial cells (HUVECs). The results showed lower RhoGDIα activity at the downstream of HUVECs (the region from the edge of the nucleus to the edge of the cell along with the flow). The overall decrease in RhoGDIα activity was inhibited by Y156A-mutant, whereas the polarized RhoGDIα and Rac1 activity were blocked by S101A/S174A mutant. It is concluded that the Tyr156 phosphorylation mainly mediates shear stress-induced overall RhoGDIα activity, while Ser101/Ser174 phosphorylation mediates its polarization. This study demonstrates that differential phosphorylation of RhoGDIα regulates shear stress-induced spatial RhoGDIα activation, which could be a potential target to control cell migration.     

Integrated risk assessment of potentially toxic elements and particle pollution in urban road dust of megacity of Pakistan

Abstract

Potentially toxic elements and particulate matter (PM) in the ecosystem are regarded as extremely hazardous because of their persistence, toxicity and bioaccumulative characteristics. Therefore, present study was conducted to estimate the ecological and human health risks of potentially toxic elements (Cu, Mn, Pb, Cd and Ni) and particle pollution (TSP, PM₁₀ and PM_2.5) at 2 and 60 m roadside distance from 15 different sites at dust polluted megacity of Pakistan. The AQI assessments suggested that the majority of sites were found unhealthy for sensitive at 2 and 60 m roadside distance, which reveals that that quality of road pavement and streets are far below than the required standards resulting huge quantity of dust particles suspended in air by natural and anthropogenic activities. The maximum geo-accumulation index (I _geo) values (1.47 and 0.52) and pollution index (PI) values (4.18 and 2.15) were observed for Ni at 2 and 60 m distance away from the muddy edge of the roads. Similarly, maximum contamination factor (CF) values (24.5 and 94.5) and ecological risk index (ERI) values (4.11 and 3.15) were found for Cd at 2 and 60 m. The I _geo and PI indicated that the road dust at a distance of 2 m was relatively more contaminated as compared to 60 m roadside distance. Highest cancer risk (CR) values (2.33 adult and 10.9 for children) were observed for Pb at 2 m, while highest CR values (1.21 for adult and 5.67 for children) at 60 m distance. No probable health risk was observed as the total hazard index (HIexp) of all potentially toxic elements was <1. However, children were appeared to be more susceptible to potentially toxic elements. Based on the results, we believe that the exponential increase in traffic load and industries have aggravated the pollution level and it is expected to be increased in the future.     

Microbial alginate production,modification and its applications

Alginate is an important polysaccharide used widely in the food, textile, printing and pharmaceutical industries for its viscosifying, and gelling properties. All commercially produced alginates are isolated from farmed brown seaweeds. These algal alginates suffer from heterogeneity in composition and material properties. Here, we will discuss alginates produced by bacteria; the molecular mechanisms involved in their biosynthesis; and the potential to utilize these bacterially produced or modified alginates for high-value applications where defined material properties are required.