Variability over time and correlates of cholesterol and blood pressure in systemic lupus erythematosus: a longitudinal cohort study

Introduction  

Total cholesterol (TC) and blood pressure (BP) are likely to take a dynamic course over time in patients with systemic lupus erythematosus (SLE). This would have important implications in terms of using single-point-in-time measurements of these variables to assess coronary artery disease (CAD) risk. The objective of this study was to describe and quantify variability over time of TC and BP among patients with SLE and to determine their correlates.     

Expression of Mitochondrial Regulators PGC1α and TFAM as Putative Markers of Subtype and Chemoresistance in Epithelial Ovarian Carcinoma

Epithelial ovarian carcinoma (EOC), the major cause of gynaecological cancer death, is a heterogeneous disease classified into five subtypes. Each subtype has distinct clinical characteristics and is associated with different genetic risk factors and molecular events, but all are treated with surgery and platinum/taxane regimes. Tumour progression and chemoresistance is generally associated with major metabolic alterations, notably altered mitochondrial function(s). Here, we report for the first time that the expression of the mitochondrial regulators PGC1α and TFAM varies between EOC subtypes; furthermore, we have identified a profile in clear-cell carcinoma consisting of undetectability of PGC1α/TFAM, and low ERα/Ki-67. By contrast, high-grade serous carcinomas were characterised by a converse state of PGC1α/TFAM, ERα positivity and a high Ki-67 index. Interestingly, loss of PGC1α/TFAM and ERα was found also in a non-clear cell EOC cell line made highly resistant to platinum in vitro. Similar to clear-cell carcinomas, these resistant cells also showed accumulation of glycogen. Altogether, our data provide mechanistic insights into the chemoresistant nature of ovarian clear-cell carcinomas. Furthermore, these findings corroborate the need to take into account the diversity of EOC and to develop subtype specific treatment strategies.     

Ectopic expression of an osmotin gene leads to enhanced salt tolerance in transgenic chilli pepper (<Emphasis Type="Italic">Capsicum annum</Emphasis> L.)

Plants, when exposed to abiotic or biotic stress, produce several pathogenesis-related proteins to counteract the effects of stress. Osmotin is one of the important pathogenesis-related proteins induced during several stress conditions. We have developed improved salt stress tolerant transgenic chilli pepper plants (Capsicum annum L. var. Aiswarya 2103) by ectopic expression of the Nicotiana tabaccum osmotin gene using Agrobacterium tumefaciens EHA105 as a vector. Four-week-old chilli pepper leaves were used as an explant and A. tumefaciens EHA105 harboring pBINASCOSM plasmid that contains osmotin gene under the control of CaMV 35S promoter and npt II as a selectable marker was used in co-cultivation. Transgene integration and expression were analyzed using molecular, immunochemical, and biochemical assays. PCR and Southern blot analysis confirmed that osmotin gene has been successfully integrated into the genome of chilli pepper plants. The osmotin gene was stably segregated and expressed in T₂ generation transgenic chilli pepper plants, and it was confirmed by Western blot analysis. Biochemical assays of these putative transgenic plants revealed enhanced levels of chlorophyll, proline, glycinebetaine, APX, SOD, DHAR, MDHAR, GR, and relative water content. Yield potential of the putative transgenic chilli pepper plants was evaluated under salinity stress conditions in a green house. The putative transgenic chilli pepper plants overexpressing the osmotin gene were morphologically similar to wild-type plants and produced 3.32 kg chilli pepper fruits per plant at 300 mM NaCl concentration.     

A sticky situation: CCN1 promotes both proliferation and apoptosis of cancer cells

Connective tissue growth factor (CTGF/CCN2) is overexpressed in diabetes. Diabetic rats possess myocardial and cardiomyocyte hypertrophy. In a recent report, Wang and colleagues (Am J Physiol Cell Physiol. 2009 Jul 22. [Epub ahead of print]) show that CCN2 directly mediates cardiomyocyte hypertrophy as well as that induced by high glucose and fatty acid. CCN2 acted via the TrkA receptor. These data are the subject of this commentary, and emphasize that CCN2 may be an excellent target for therapy in diabetes.     

Cloning and characterization of a SnRK1-encoding gene from <Emphasis Type="Italic">Malus hupehensis</Emphasis> Rehd. and heterologous expression in tomato

Sucrose non-fermenting-1-related protein kinase-1 (SnRK1) plays an important role in metabolic regulation in plant. To understand the molecular mechanism of amino acids and carbohydrate metabolism in Malus hupehensis Rehd. var. pinyiensis Jiang (Pingyi Tiancha, PYTC), a full-length cDNA clone encoding homologue of SnRK1 was isolated from PYTC by Rapid Amplification of cDNA Ends (RACE). The clone, designated as MhSnRK1, contains 2063 nucleotides with an open reading frame of 1548 nucleotides. The deduced 515 amino acids showed high identities with other plant SnRK1 genes. Quantitative real-time PCR analysis revealed this gene was expressed in roots, stems and leaves. Exposing seedlings to nitrate caused and initial decrease in expression of the MhSnRK1 gene in roots, leaves and stems in short term. Ectopic expression of MhSnRK1 in tomato mainly resulted in higher starch content in leaf and red-ripening fruit than wild-type plants. This result supports the hypothesis that overexpression of SnRK1 causes the accumulation of starch in plant cells. All the results suggest that MhSnRK1 may play important roles in carbohydrate and amino acid metabolisms.     

Growth and water relations in a central North Carolina population of <Emphasis Type="Italic">Microstegium vimineum</Emphasis> (Trin.) A. Camus

The ability of an invasive plant to occupy new areas is often attributed to both morphological and physiological plasticities that allow them to remain viable over a wide range of environmental conditions. Studies addressing the ecological requirements of Microstegium vimineum often consider soil moisture or soil moisture along with other factors as important explanatory components for the establishment and persistence of this invasive monocot. However, controlled studies specifically targeting water relations in M. vimineum are needed. Therefore, the purpose of this study was to determine how different water availabilities influence the growth and physiological performance of M. vimineum. This study utilized experimental microcosms to achieve different water availabilities including low soil moisture (<15% water), moderate soil moisture (ca. 20–30%), and flooded conditions. While both flooded and low soil moisture resulted in diminished growth, M. vimineum still survived under these conditions. Physiological processes including C₄ metabolism, minimum stress under low water conditions, and the ability to increase tissue rigidity may confer some advantages to M. vimineum during periods of limiting water conditions. Similarly, the proportionally low root biomass, shallow root structure, and its ability to maintain stable water relations during flooding and/or soil waterlogging may facilitate M. vimineum’s ability to invade mesic habitats. It is likely, therefore, that the capacity to tolerate both low soil moistures and flooded conditions has enhanced the ability of M. vimineum to populate disturbed systems in central North Carolina.     

Severe and rapid population declines in exotic birds

A particularly vexing phenomenon within invasion ecology is the occurrence of spontaneous collapses within seemingly well-established exotic populations. Here, we assess the frequency of collapses among 68 exotic bird populations established in Hawaii, Puerto Rico, Los Angeles and Miami. Following other published definitions, we define a ‘collapse’ as a decline in abundance of ≥90 % within ≤10 years that lasts for at least 3 years. We show that 44 of the 68 exotic bird populations have exhibited declines at some point within their time series. Sixteen of the populations declined sufficiently to be defined as collapsed. It took on average 3.8 ± 1.8 years for populations to decline into a collapsed state, and this state persisted on average for 7.1 ± 6.3 years across (collapsed) populations. We compared the severity and duration of declines across all 44 declining populations according to taxonomic Order and geographic region. Neither variable explained substantial variation in the metrics of collapse. Our results indicate that severe, rapid, and persistent population declines may be common among exotic populations. We suggest that incorporating the probability and persistence of collapses into management decisions can inform efforts to enact control or eradication measures. We also suggest that applying our approach to other taxa and locations is crucial for improving our understanding of when and where collapses are likely to occur.     

The ubiquitin C‐terminal hydrolase UCH‐L1 promotes bacterial invasion by altering the dynamics of the actin cytoskeleton

Invasion of eukaryotic target cells by pathogenic bacteria requires extensive remodelling of the membrane and actin cytoskeleton. Here we show that the remodelling process is regulated by the ubiquitin C‐terminal hydrolase UCH‐L1 that promotes the invasion of epithelial cells by Listeria monocytogenes and Salmonella enterica. Knockdown of UCH‐L1 reduced the uptake of both bacteria, while expression of the catalytically active enzyme promoted efficient internalization in the UCH‐L1‐negative HeLa cell line. The entry of L. monocytogenes involves binding to the receptor tyrosine kinase Met, which leads to receptor phosphorylation and ubiquitination. UCH‐L1 controls the early membrane‐associated events of this triggering cascade since knockdown was associated with altered phosphorylation of the c‐cbl docking site on Tyr1003, reduced ubiquitination of the receptor and altered activation of downstream ERK1/2‐ and AKT‐dependent signalling in response to the natural ligand Hepatocyte Growth Factor (HGF). The regulation of cytoskeleton dynamics was further confirmed by the induction of actin stress fibres in HeLa expressing the active enzyme but not the catalytic mutant UCH‐L1_C90S. These findings highlight a previously unrecognized involvement of the ubiquitin cycle in bacterial entry. UCH‐L1 is highly expressed in malignant cells that may therefore be particularly susceptible to invasion by bacteria‐based drug delivery systems.