Differential regulation of oestrogen receptor β isoforms by 5' untranslated regions in cancer

Oestrogen receptors (ERs) are critical regulators of the behaviour of many cancers. Despite this, the roles and regulation of one of the two known ERs - ERβ- are poorly understood. This is partly because analyses have been confused by discrepancies between ERβ expression at mRNA and proteins levels, and because ERβ is expressed as several functionally distinct isoforms. We investigated human ERβ 5' untranslated regions (UTRs) and their influences on ERβ expression and function. We demonstrate that two alternative ERβ 5'UTRs have potent and differential influences on expression acting at the level of translation. We show that their influences are modulated by cellular context and in carcinogenesis, and demonstrate the contributions of both upstream open reading frames and RNA secondary structure. These regulatory mechanisms offer explanations for the non-concordance of ERβ mRNA and protein. Importantly, we also demonstrate that 5'UTRs allow the first reported mechanisms for differential regulation of the expression of the ERβ isoforms 1, 2 and 5, and thereby have critical influences on ERβ function.     

The ��-subunit of ATP synthase is involved in cellular uptake and resecretion of apoA-I but does not control apoA-I-induced lipid efflux in adipocytes

Cellular uptake and resecretion of apoA-I (apoA-I recycling) could be an important factor in determining the circulating plasma levels of apoA-I and/or HDL. Using a novel method to study protein recycling, we have recently demonstrated recycling of apoA-I by adipocytes and suggested that this is a receptor mediated process independent of ABCA1 function. In the present study, it is shown that apoA-I recycling by adipocytes can be blocked by a monoclonal antibody against the β-subunit of ATP synthase, a protein that had been previously identified as an apoA-I receptor. Investigation of the cellular recycling of two other proteins, an apolipoprotein and a small globular protein, showed that recycling of apoA-I is a selective process. The present study also shows that blocking apoA-I recycling has no effect on the rate of apoA-I-induced cholesterol or phospholipid efflux. It is concluded that cellular recycling of apoA-I is a selective process that involves the ectopically expressed β-subunit of ATP synthase. The physiological function of apoA-I recycling remains to be elucidated. However, this study shows that the process of apoA-I uptake and resecretion is not required for apoA-I lipidation.     

Effect of environmental parameters on immune response of the Indian spiny lobster, Panulirus homarus (Linnaeus, 1758)

The high export value of the Indian spiny lobster Panulirus homarus increasingly attracts the aquaculturists for farming and fattening. However, lack of knowledge on the effect of environmental parameters on the immune system of this animal could result in high mortality, which ultimately may cause major loss to the industry. Here, we report the effect of salinity (20, 25, 35, 40, and 45 per thousand), pH (5.0, 8.0, and 9.5), dissolved oxygen (DO) (1 and 5 mg L(-1)), and ammonia-N concentration (0, 0.5, 1.5 and 3 mg L(-1)) on the immune response of P. homarus measured in the haemolymph in terms of Total Haemocyte Count (THC), phenoloxidase (PO) activity, and NBT-reduction. Our data showed significant reduction (P<0.05) in THC, and NBT-reduction at lower (20 per thousand) and higher (45 per thousand) salinities. However, PO activity showed significant disparity, showing an increasing trend from 20 to 45 per thousand. Significant reduction (P<0.05) in THC and PO activity under acidic and alkaline conditions, under hypoxic condition (1 mg L(-1)), and at the higher ammonia-N concentrations than their respective optimal conditions were observed. Thus, suggesting that extreme environmental parameters can induce modifications in the immune system of the spiny lobster P. homarus, which may enhance their susceptibility to opportunistic pathogens. The humoral parameters such as THC, PO activity, and NBT-reduction can be used as potential stress indicators for healthy management of spiny lobsters.     

Oviposition Site-Selection by Bactrocera dorsalis Is Mediated through an Innate Recognition Template Tuned to γ-Octalactone

Innate recognition templates (IRTs) in insects are developed through many years of evolution. Here we investigated olfactory cues mediating oviposition behavior in the oriental fruit fly, Bactrocera dorsalis, and their role in triggering an IRT for oviposition site recognition. Behavioral assays with electrophysiologically active compounds from a preferred host, mango, revealed that one of the volatiles tested, γ-octalactone, had a powerful effect in eliciting oviposition by gravid B. dorsalis females. Electrophysiological responses were obtained and flies clearly differentiated between treated and untreated substrates over a wide range of concentrations of γ-octalactone. It triggered an innate response in flies, overriding inputs from other modalities required for oviposition site evaluation. A complex blend of mango volatiles not containing γ-octalactone elicited low levels of oviposition, whereas γ-octalactone alone elicited more oviposition response. Naïve flies with different rearing histories showed similar responses to γ-octalactone. Taken together, these results indicate that oviposition site selection in B. dorsalis is mediated through an IRT tuned to γ-octalactone. Our study provides empirical data on a cue underpinning innate behavior and may also find use in control operations against this invasive horticultural pest.     

Studies on the partial characterization of extracted glycosaminoglycans from fish waste and its potentiality in modulating obesity through in-vitro and in-vivo

Glycoconjugate Journal - Glycosaminoglycans (GAGs) are bioactive polysaccharides or glycoconjugates found in the fish waste having significant health impacts. In the present study it has been...     

Packaging Strategies That Save Food: A Research Agenda for 2030

Thoroughly considering and optimizing packaging systems can avoid food loss and waste. We suggest a number of issues that must be explored and review the associated challenges. Five main issues were recognized through the extensive experience of the authors and engagement of multiple stakeholders. The issues promoted are classified as follows: (1) identify and obtain specific data of packaging functions that influence food waste; (2) understand the total environmental burden of product/package by considering the trade‐off between product protection and preservation and environmental footprint; (3) develop understanding of how these functions should be treated in environmental footprint evaluations; (4) improve packaging design processes to also consider reducing food waste; and (5) analyze stakeholder incentives to reduce food loss and waste. Packaging measures that save food will be important to fulfill the United Nations Sustainable Development goal to halve per capita global food waste at the retail and consumer levels and to reduce food losses along production and supply chains.     

Flavone-based analogues inspired by the natural product simocyclinone D8 as DNA gyrase inhibitors

The increasing occurrence of drug-resistant bacterial infections in the clinic has created a need for new antibacterial agents. Natural products have historically been a rich source of both antibiotics and lead compounds for new antibacterial agents. The natural product simocyclinone D8 (SD8) has been reported to inhibit DNA gyrase, a validated antibacterial drug target, by a unique catalytic inhibition mechanism of action. In this work, we have prepared simplified flavone-based analogues inspired by the complex natural product and evaluated their inhibitory activity and mechanism of action. While two of these compounds do inhibit DNA gyrase, they do so by a different mechanism of action than SD8, namely DNA intercalation.     

HYPERSALINE SOIL SUPPORTS A DIVERSE COMMUNITY OF DUNALIELLA (CHLOROPHYCEAE)1

Numerous isolates of the green halophile Dunaliella were studied as part of a survey of microbial diversity at the Great Salt Plains (GSP) in Oklahoma, USA. The GSP is a large (～65 km²) salt flat with extreme temporal and spatial fluctuations in salinity and temperature. Although the flagellate halophile Dunaliella is common worldwide, nearly all cultured isolates are from saline habitats that are primarily aquatic rather than primarily terrestrial. The diverse GSP Dunaliella strains exhibit three morphotypes: a predominantly motile form, a motile form with a prominent palmelloid phase (nonmotile, mucilage rich), and a palmelloid form with a weakly motile phase. All had broad salinity optima well below typical in situ salinities at the GSP, and two of the palmelloid isolates grew as well in freshwater as in highly saline media. Molecular phylogenetic and evolutionary analyses revealed that Dunaliella from the GSP (and two similar habitats in the Great Basin, USA) are allied with D. viridis Teodor. but possess phylogenetic diversity in excess of existing global isolates from aquatic habitats. In addition, isolates from primarily terrestrial habitats exhibit statistically higher rates of nucleotide substitution than the phylogenetically homogeneous set of primarily aquatic Dunaliella taxa. We hypothesize that dynamically extreme saline soil habitats may select for different and more diverse Dunaliella lineages than more stable saline aquatic habitats. We also propose Dunaliella as a tractable microbial model for in situ testing of evolutionary and phylogeographic hypotheses.     

A lysine-rich region within fungal BAG domain-containing proteins mediates a novel association with ribosomes

Heat shock protein 70 (Hsp70) is a highly conserved molecular chaperone that assists in the folding of nascent chains and the repair of unfolded proteins through iterative cycles of ATP binding, hydrolysis, and nucleotide exchange tightly coupled to polypeptide binding and release. Cochaperones, including nucleotide exchange factors (NEFs), modulate the rate of ADP/ATP exchange and serve to recruit Hsp70 to distinct processes or locations. Among three nonrelated cytosolic NEFs in Saccharomyces cerevisiae, the Bag-1 homolog SNL1 is unique in being tethered to the endoplasmic reticulum (ER) membrane. We demonstrate here a novel physical association between Snl1 and the intact ribosome. This interaction is both independent of and concurrent with binding to Hsp70 and is not dependent on membrane localization. The ribosome binding site is identified as a short lysine-rich motif within the amino terminus of the Snl1 BAG domain distinct from the Hsp70 interaction region. Additionally, we demonstrate a ribosome association with the Candida albicans Snl1 homolog and localize this putative NEF to a perinuclear/ER membrane, suggesting functional conservation in fungal BAG domain-containing proteins. We therefore propose that the Snl1 family of NEFs serves a previously unknown role in fungal protein biogenesis based on the coincident recruitment of ribosomes and Hsp70 to the ER membrane.