ABA in bryophytes: how a universal growth regulator in life became a plant hormone?

Abscisic acid (ABA) is not a plant-specific compound but one found in organisms across kingdoms from bacteria to animals, suggesting that it is a ubiquitous and versatile substance that can modulate physiological functions of various organisms. Recent studies have shown that plants developed an elegant system for ABA sensing and early signal transduction mechanisms to modulate responses to environmental stresses for survival in terrestrial conditions. ABA-induced increase in stress tolerance has been reported not only in vascular plants but also in non-vascular bryophytes. Since bryophytes are the key group of organisms in the context of plant evolution, clarification of their ABA-dependent processes is important for understanding evolutionary adaptation of land plants. Molecular approaches using Physcomitrella patens have revealed that ABA plays a role in dehydration stress tolerance in mosses, which comprise a major group of bryophytes. Furthermore, we recently reported that signaling machinery for ABA responses is also conserved in liverworts, representing the most basal members of extant land plant lineage. Conservation of the mechanism for ABA sensing and responses in angiosperms and basal land plants suggests that acquisition of this mechanism for stress tolerance in vegetative tissues was one of the critical evolutionary events for adaptation to the land. This review describes the role of ABA in basal land plants as well as non-land plant organisms and further elaborates on recent progress in molecular studies of model bryophytes by comparative and functional genomic approaches.     

NF-κB potentiates tumor growth by suppressing a novel target LPTS

Background

Chronic inflammation is causally linked to the carcinogenesis and progression of most solid tumors. LPTS is a well-identified tumor suppressor by inhibiting telomerase activity and cancer cell growth. However, whether and how LPTS is regulated by inflammation signaling is still incompletely elucidated.

Methods

Real-time PCR and western blotting were used to determine the expression of p65 and LPTS. Reporter gene assay, electrophoretic mobility shift assay and chromatin immunoprecipitation were performed to decipher the regulatory mechanism between p65 and LPTS. Cell counting kit-8 assays and xenograt models were used to detect p65-LPTS-regulated cancer cell growth in vitro and in vivo, respectively.

Results

Here we for the first time demonstrated that NF-κB could inhibit LPTS expression in the mRNA and protein levels in multiple cancer cells (e.g. cervical cancer and colon cancer cells). Mechanistically, NF-κB p65 could bind to two consensus response elements locating at ?1143/?1136 and ?888/?881 in the promoter region of human LPTS gene according to EMSA and ChIP assays. Mutation of those two binding sites rescued p65-suppressed LPTS promoter activity. Functionally, NF-κB regulated LPTS-dependent cell growth of cervical and colon cancers in vitro and in xenograft models. In translation studies, we verified that increased p65 expression was associated with decreased LPTS level in multiple solid cancers.

Conclusions

Taken together, we revealed that NF-κB p65 potentiated tumor growth via suppressing a novel target LPTS. Modulation of NF-κB-LPTS axis represented a potential strategy for treatment of those inflammation-associated malignancies.

     

Does a targeting ligand influence nanoparticle tumor localization or uptake?

Inclusion of a tumor-targeting molecule in nanosized delivery systems increases their in vivo efficacy. However, the biodistribution and pharmacokinetics of the uptake of such particles have not yet been well addressed. Several recent papers have suggested that tumor-targeting ligands function primarily to increase intracellular uptake of the nanocomplex and do not influence tumor localization. However, other reports indicate that they do play a role in the accumulation in the tumor. One difference might be the presence or absence of poly-[ethylene glycol] (PEG) in the complex and its impact on the enhanced permeability and retention (EPR) effect. Further studies are clearly needed to more fully elucidate the influence of composition on tumor-targeted, systemic delivery of nanoparticles.     

Does clinical research provide any "direct individual benefit"?

The European Commission and Parliament have promulgated a directive on clinical research (2001/20/CE) in April 2001. Its provisions have to be incorporated in all national laws by May 2004. Accordingly, the French " loi Huriet " (a law passed in 1988 organizing clinical research in France) had to be revised. During the process, it appeared that a key issue was the suppression of a distinction made by this law between research with and without " direct individual benefit ", a French specificity, as the directive recommends rather the assessment of the risk/benefit ratio. In order to harmonize the French legislation with the other European laws, and to suppress a set of provisions which have been repeatedly attacked during the last ten years, the French members of parliament have voted on October 2003 a new law which, among other important modifications, suppress that distinction.     

Can there be a "cultural epidemiology"?

A brief excursion through the history of social medicine suggests that, at least in principle, epidemiology and anthropology are natural allies in the study of disease in human populations. In practice, however, this alliance has been limited and remains problematic. This article examines the possibilities for interdisciplinary research, taking cancer epidemiology as a case in point. I argue, on the basis of participant-observation over a period of nearly two years in the epidemiology department of a medical research institute in Catalonia (Spain), that bioscientific uses of the concept of culture have led, disappointingly, to its reification as "beliefs" and its incorporation into the naturalist epistemology of Western institutional medicine. The unfortunate consequence is the medicalization of culture understood as "difference," which often stands in for social class.     

Switching TGFβ from a tumor suppressor to a tumor promoter

TGFβ acts as a potent tumor suppressor and tumor promoter in a context dependent manner. Tumor suppressive functions include inhibition of cell proliferation, induction of apoptosis and regulation of autophagy. As tumors develop they switch their response to TGFβ and utilise this factor as a potent promoter of cell motility, invasion, metastasis and tumor stem cell maintenance. These multifactorial tumor influencing actions of TGFβ involve regulation of an increasing number of signal transduction pathways employing a diverse range of signaling molecules. Understanding the molecular mechanisms of how tumor cells respond to TGFβ and switch their response to this cytokine during disease progression is vital for both the development and the informed use of potentially powerful TGFβ targeted therapeutics.     

Amborella not a "basal angiosperm"? Not so fast

The sequence of the plastid genome of Amborella trichopoda, the putative sister to all other extant angiosperms, was recently reported (Molecular Biology and Evolution 20: 1499-1505). Goremykin et al. used sequence data for 61 plastid genes from Amborella and 12 other embryophytes in phylogenetic analyses and concluded that Amborella is not the sister to the remaining flowering plants; the monocots instead occupy this position. The authors attributed their results, which differ substantially from all recent phylogenetic analyses of angiosperms, to the increased character sampling (30?017 nucleotides in their aligned matrix) in their analysis relative to published studies that included fewer genes but more taxa. We hypothesized that the difference in topology is not due to limited character sampling in previous studies but to limited taxon sampling in the analysis by Goremykin et al. To test this, we conducted a series of phylogenetic analyses using a three-gene, 12 (or more)-taxon data set to evaluate the topological effects of (i) including three vs. 61 genes for (nearly) the same set of taxa, (ii) analyzing different codon positions, (iii) substituting representatives of other basal lineages for Amborella, (iv) replacing the grasses used to represent the monocots with other monocots, selected either for their phylogenetic position or randomly, and (v) adding other basal taxa-Nymphaea, Austrobaileya, magnoliids, and monocots-to the 12-taxon data set. Our results demonstrate that the "monocots basal" topology obtained by Goremykin et al. is not due to increased character sampling of the plastid genome; their topology was obtained using only two plastid genes or two plastid genes and one nuclear gene. This topology was also retained when either Nymphaea or Austrobaileya was substituted for Amborella, demonstrating that any of the three basal lineages will attach to Calycanthus for lack of any other close branch. Furthermore, the "monocots basal" topology is not robust to changes in sampling of monocots. Simply adding Oncidium, for example, places Amborella sister to the other angiosperms. Thus, limited taxon sampling, focusing on organisms with complete genome sequences, can lead to artifactual results.     

Does any enzyme follow the Michaelis—Menten equation?

Summary A literature search has been conducted to see to what extent steady-state kinetics studies in the period 1965–1976 have revealed deviations from Michaelis—Menten kinetics. It was found that over 800 enzymes have been reported as giving complex curves for a variety of reasons and a group by group classification of all these enzymes has been carried out listing all the types of variations reported and the authors' explanations. In addition, for highly complex curves, we have determined the minimum degree of the rate equation. There were very few determined attempts to demonstrate adherence to the Michaelis—Menten equation over a wide variety of experimental conditions and substrate concentration and almost invariably detailed experimental work revealed unsuspected complexities. For these reasons, it is concluded that the assumption that most enzymes follow the Michaelis—Menten equation can not be supported by an appeal to the literature.     

Does income growth relocate ecological footprint?

The aim of this paper is to investigate whether countries tend to relocate their ecological footprint as they grow richer. The analysis is carried out for a panel of 116 countries by employing the production and import components of the ecological footprint data of the Global Footprint Network for the period 2004–2008. With few exceptions, the existing Environmental Kuznets Curve (EKC) literature concentrates only on the income-environmental degradation nexus in the home country and neglects the negative consequences of home consumption spilled out. Controlling for the effects of openness to trade, biological capacity, population density, industry share and energy per capita as well as stringency of environmental regulation and environmental regulation enforcement, we detect an EKC-type relationship only between per capita income and footprint of domestic production. Within the income range, import footprint is found to be monotonically increasing with income. Moreover, we find that domestic environmental regulations do not influence country decisions to import environmentally harmful products from abroad; but they do affect domestic production characteristics. Hence, our findings indicate the importance of environmental regulations and provide support for the “Pollution Haven” and “Race-to-the-Bottom” hypotheses.     

Does CD95 have tumor promoting activities?

CD95 (APO-1/Fas) is an important inducer of the extrinsic apoptosis signaling pathway and therapy induced apoptosis of many tumor cells has been linked to the activity of CD95. Changes in the expression of CD95 and/or its ligand CD95L are frequently found in human cancer. The downregulation or mutation of CD95 has been proposed as a mechanism by which cancer cells avoid destruction by the immune system through reduced apoptosis sensitivity. CD95 has therefore been viewed as a tumor suppressor. Furthermore, increased CD95L concentration in tumor patients has been linked to tumor cells killing infiltrating lymphocytes in a process called "the tumor counter-attack". Recent data have illuminated unknown activities of CD95 in tumor cells with downregulated or mutated CD95 in the presence of increased CD95L. Under these conditions the stimulation of CD95 signals nonapoptotic pathways, activating NF-kappaB and MAP kinases for example, which may result in the induction of tumorigenic or prosurvival genes. A new model of CD95 functions is proposed in which CD95 is converted from a tumor suppressor to a tumor promotor by a single point mutation in one of the CD95 alleles, a situation frequently found in advanced human cancer, resulting in apoptosis resistance and activation of tumorigenic pathways.     

Does the tumor microenvironment influence radiation-induced apoptosis?

Cytotoxic anti-cancer agents induce apoptosis in tumor and normal tissues. Therefore, it is important to investigate which factors determine these apoptotic processes and hence their likely impact on therapeutic gain. Radiation-induced apoptosis in tumors may be inhibited due to mutations of apoptotic elements or to tumor microenvironmental conditions arising from vascular insufficiency. Tumors typically contain regions of hypoxia, low glucose and acidosis. Hypoxic cells compromise treatment partly because of reduced fixation of damage during radiotherapy and partly because they promote a more malignant phenotype. There is also evidence that hypoxia may inhibit apoptosis. For some cell types, concurrent hypoxia may modulate radiation-induced apoptosis while, for others, post-irradiation hypoxia may be required. This may reflect the activity of different apoptotic pathways. Pathways involving mitochondrial components as well as regulation of SAPK and Fas have been implicated. In addition, several key stages in apoptosis are sensitive to depletion of cellular energy reserves, which results from hypoxia and low glucose conditions. There is also evidence that low pH in tumors can interfere with radiation-induced apoptosis, partly through cell cycle arrest and other undefined mechanisms. Conclusions: Hypoxia, low glucose and acidosis influence radiation-induced apoptosis and thus may be detrimental to radiotherapy.