BAG3 regulates total MAP1LC3B protein levels through a translational but not transcriptional mechanism

Autophagy is mainly regulated by post-translational and lipid modifications of ATG proteins. In some scenarios, the induction of autophagy is accompanied by increased levels of certain ATG mRNAs such as MAP1LC3B/LC3B, ATG5 or ATG12. However, little is known about the regulation of ATG protein synthesis at the translational level. The cochaperone of the HSP70 system BAG3 (BCL2-associated athanogene 3) has been associated to LC3B lipidation through an unknown mechanism. In the present work, we studied how BAG3 controls autophagy in HeLa and HEK293 cells. Our results showed that BAG3 regulates the basal amount of total cellular LC3B protein by controlling its mRNA translation. This effect was apparently specific to LC3B because other ATG protein levels were not affected. BAG3 knockdown did not affect LC3B lipidation induced by nutrient deprivation or proteasome inhibition. We concluded that BAG3 maintains the basal amount of LC3B protein by controlling the translation of its mRNA in HeLa and HEK293 cells.     

Genomic Characterization of Phenylalanine Ammonia Lyase Gene in Buckwheat

Phenylalanine Ammonia Lyase (PAL) gene which plays a key role in bio-synthesis of medicinally important compounds, Rutin/quercetin was sequence characterized for its efficient genomics application. These compounds possessing anti-diabetic and anti-cancer properties and are predominantly produced by Fagopyrum spp. In the present study, PAL gene was sequenced from three Fagopyrum spp. (F. tataricum, F. esculentum and F. dibotrys) and showed the presence of three SNPs and four insertion/deletions at intra and inter specific level. Among them, the potential SNP (position 949^th bp G>C) with Parsimony Informative Site was selected and successfully utilised to individuate the zygosity/allelic variation of 16 F. tataricum varieties. Insertion mutations were identified in coding region, which resulted the change of a stretch of 39 amino acids on the putative protein. Our Study revealed that autogamous species (F. tataricum) has lower frequency of observed SNPs as compared to allogamous species (F. dibotrys and F. esculentum). The identified SNPs in F. tataricum didn’t result to amino acid change, while in other two species it caused both conservative and non-conservative variations. Consistent pattern of SNPs across the species revealed their phylogenetic importance. We found two groups of F. tataricum and one of them was closely related with F. dibotrys. Sequence characterization information of PAL gene reported in present investigation can be utilized in genetic improvement of buckwheat in reference to its medicinal value.     

Source Odor,Intensity, and Exposure Pattern Affect Antipredatory Responses in the Subterranean Rodent Ctenomys talarum

Predation is a strong selective force, and prey species may show specific adaptations that allow recognition, avoidance, and defense against predators. Facing a situation of predatory risk, anxiety constitutes a reaction of adaptive value, allowing to evaluate the potential risk of this encounter as well as to generate a physiological and behavioral response. Previous studies in the subterranean rodent Ctenomys talarum revealed that exposure to predator odors (urine or fur) generates an anxiety state and induces behavioral changes. However, no differences between the responses generated by both odor sources were observed, although fur odors may indicate a higher level of predatory immanence. Therefore, the aim of this study was to evaluate the behavioral and physiological responses of C. talarum to different intensities of predator odors (urine and fur) and to the repeated exposition to the same odorous stimulus. When comparing the highest behavioral effects elicited by both predatory odors on C. talarum, our study supports the assumption that fur odors are more anxiogenic than urine, while the former provoked significant changes in the distance traveled, the number of arm entries and time in transparent arms in the elevated plus maze; cat urine only caused slight changes on those behavioral parameters. Furthermore, we also found that the intensity of natural predator odor presented to tuco‐tucos has a role on the appearance of defensive behaviors, although an amount‐dependent relationship between predator odor and anxiety levels was not observed. Finally, while individuals exposed for 1 day to fur odor displayed an evident anxiety state, those exposed repeatedly for 5 consecutive days did not differ with the control group in their behavioral response, indicating a clear habituation to the predatory cue. In our intensity and habituation experiments, we did not find differences in the measured physiological parameters among control individuals, exposed to different cues intensity (urine and fur odor) and exposed only once or for 5 days to fur odor. These results provide valuable evidence that the types of predatory odor, along with the frequency of exposition, are important determinants of the appearance, strength, and extinction of defensive behaviors in the subterranean rodent C. talarum.     

Ecological genetics of Italian peach‐potato aphid (Myzus persicae) populations in relation to geography,dispersal and insecticide resistance as studied using microsatellite and resistance markers

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The contribution of <Emphasis Type="Italic">Potamogeton crispus</Emphasis> to the phosphorus budget of an urban shallow lake: Lake Monger,Western Australia

Lake Monger (Perth, Western Australia) is a highly eutrophic lake, characterised by very low species richness of macrophytes with the dominance of Potamogeton crispus. Mesocosm experiments were performed using water and plants collected from the lake to determine the effects of vegetation decay on the phosphorus (P) concentrations in the overlying waters. After 2 weeks of experimental incubation of mesocosms with and without re-oxygenation, P concentrations in the water column were significantly higher, showing a quite similar effect of P. crispus on the phosphorus release in different mesocosms. The results of our study provide clear evidence that the P concentrations in overlying waters mainly depend upon the plant P content and developmental stage. Although many sources contribute to the nutrient load of Lake Monger, macrophyte harvesting, prior to its senescence, might constitute a significant in-lake measure for reducing the internal P load.     

Urokinase links plasminogen activation and cell adhesion by cleavage of the RGD motif in vitronectin

Components of the plasminogen activation system including urokinase (uPA), its inhibitor (PAI‐1) and its cell surface receptor (uPAR) have been implicated in a wide variety of biological processes related to tissue homoeostasis. Firstly, the binding of uPA to uPAR favours extracellular proteolysis by enhancing cell surface plasminogen activation. Secondly, it promotes cell adhesion and signalling through binding of the provisional matrix protein vitronectin. We now report that uPA and plasmin induces a potent negative feedback on cell adhesion through specific cleavage of the RGD motif in vitronectin. Cleavage of vitronectin by uPA displays a remarkable receptor dependence and requires concomitant binding of both uPA and vitronectin to uPAR. Moreover, we show that PAI‐1 counteracts the negative feedback and behaves as a proteolysis‐triggered stabilizer of uPAR‐mediated cell adhesion to vitronectin. These findings identify a novel and highly specific function for the plasminogen activation system in the regulation of cell adhesion to vitronectin. The cleavage of vitronectin by uPA and plasmin results in the release of N‐terminal vitronectin fragments that can be detected in vivo, underscoring the potential physiological relevance of the process.     

A specific inhibitor of lactate dehydrogenase overcame the resistance toward gemcitabine in hypoxic mesothelioma cells,and modulated the expression of the human equilibrative transporter-1

ABSTRACT

Malignant pleural mesothelioma (MPM) is a very hypoxic malignancy, and hypoxia has been associated with resistance towards gemcitabine. The muscle-isoform of lactate dehydrogenase (LDH-A) constitutes a major checkpoint for the switch to anaerobic glycolysis. Therefore we investigated the combination of a new LDH-A inhibitor (NHI-1) with gemcitabine in MPM cell lines. Under hypoxia (O₂ tension of 1%) the cell growth inhibitory effects of gemcitabine, were reduced, as demonstrated by a 5- to 10-fold increase in IC₅₀s. However, the simultaneous addition of NHI-1 was synergistic (combination index < 1). Flow cytometry demonstrated that hypoxia caused a G1 arrest, whereas the combination of NHI-1 significantly increased gemcitabine-induced cell death. Finally, the mRNA expression levels of the human equilibrative transporter-1 (hENT1) were significantly down-regulated under hypoxia, but treatment with NHI-1 was associated with a recovery of hENT1 expression. In conclusion, our data show that hypoxia increased MPM resistance to gemcitabine. However, cell death induction and modulation of the key transporter in gemcitabine uptake may contribute to the synergistic interaction of gemcitabine with the LDH-A inhibitor NHI-1 and support further studies for the rational development of this combination.