A Human-Like Senescence-Associated Secretory Phenotype Is Conserved in Mouse Cells Dependent on Physiological Oxygen

Cellular senescence irreversibly arrests cell proliferation in response to oncogenic stimuli. Human cells develop a senescence-associated secretory phenotype (SASP), which increases the secretion of cytokines and other factors that alter the behavior of neighboring cells. We show here that “senescent” mouse fibroblasts, which arrested growth after repeated passage under standard culture conditions (20% oxygen), do not express a human-like SASP, and differ from similarly cultured human cells in other respects. However, when cultured in physiological (3%) oxygen and induced to senesce by radiation, mouse cells more closely resemble human cells, including expression of a robust SASP. We describe two new aspects of the human and mouse SASPs. First, cells from both species upregulated the expression and secretion of several matrix metalloproteinases, which comprise a conserved genomic cluster. Second, for both species, the ability to promote the growth of premalignant epithelial cells was due primarily to the conserved SASP factor CXCL-1/KC/GRO-α. Further, mouse fibroblasts made senescent in 3%, but not 20%, oxygen promoted epithelial tumorigenesis in mouse xenographs. Our findings underscore critical mouse-human differences in oxygen sensitivity, identify conditions to use mouse cells to model human cellular senescence, and reveal novel conserved features of the SASP

HSC-CLAUDS survey: The star formation rate functions since z ~ 2 and comparison with hydrodynamical simulations

Star formation rate functions (SFRFs) give an instantaneous view of the distribution of star formation rates (SFRs) in galaxies at different epochs. They are a complementary and more stringent test for models than the galaxy stellar mass function, which gives an integrated view of the past star formation activity. However, the exploration of SFRFs has been limited thus far due to difficulties in assessing the SFR from observed quantities and probing the SFRF over a wide range of SFRs. We overcome these limitations thanks to an original method that predicts the infrared luminosity from the rest-frame UV/optical color of a galaxy and then its SFR over a wide range of stellar masses and redshifts. We applied this technique to the deep imaging survey HSC-CLAUDS combined with near-infrared and UV photometry. We provide the first SFR functions with reliable measurements in the high- and low-SFR regimes up to $z=2$ and compare our results with previous observations and four state-of-the-art hydrodynamical simulations.Comment: 29 pages, 19 figure

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

A high-performance matrix-matrix multiplication methodology for CPU and GPU architectures

Current compilers cannot generate code that can compete with hand-tuned code in efficiency, even for a simple kernel like matrix–matrix multiplication (MMM). A key step in program optimization is the estimation of optimal values for parameters such as tile sizes and number of levels of tiling. The scheduling parameter values selection is a very difficult and time-consuming task, since parameter values depend on each other; this is why they are found by using searching methods and empirical techniques. To overcome this problem, the scheduling sub-problems must be optimized together, as one problem and not separately. In this paper, an MMM methodology is presented where the optimum scheduling parameters are found by decreasing the search space theoretically, while the major scheduling sub-problems are addressed together as one problem and not separately according to the hardware architecture parameters and input size; for different hardware architecture parameters and/or input sizes, a different implementation is produced. This is achieved by fully exploiting the software characteristics (e.g., data reuse) and hardware architecture parameters (e.g., data caches sizes and associativities), giving high-quality solutions and a smaller search space. This methodology refers to a wide range of CPU and GPU architectures

A fluorescent hormone biosensor reveals the dynamics of jasmonate signalling in plants

Activated forms of jasmonic acid (JA) are central signals coordinating plant responses to stresses, yet tools to analyse their spatial and temporal distribution are lacking. Here we describe a JA perception biosensor termed Jas9-VENUS that allows the quantification of dynamic changes in JA distribution in response to stress with high spatiotemporal sensitivity. We show that Jas9-VENUS abundance is dependent on bioactive JA isoforms, the COI1 co-receptor, a functional Jas motif and proteasome activity. We demonstrate the utility of Jas9-VENUS to analyse responses to JA in planta at a cellular scale, both quantitatively and dynamically. This included using Jas9-VENUS to determine the cotyledon-to-root JA signal velocities on wounding, revealing two distinct phases of JA activity in the root. Our results demonstrate the value of developing quantitative sensors such as Jas9-VENUS to provide high-resolution spatiotemporal data about hormone distribution in response to plant abiotic and biotic stresses

Identification of Fluorescent Compounds with Non-Specific Binding Property via High Throughput Live Cell Microscopy

10.1371/journal.pone.0028802PLoS ONE71

Effect of Cryogrinding on Chemical Stability of the Sparingly Water-Soluble Drug Furosemide

Purpose To investigate the effect of cryogrinding on chemical stability of the diuretic agent furosemide and its mixtures with selected excipients. Methods Furosemide was ground at liquid nitrogen temperature for 30, 60, 120 and 180 min. Mixtures of furosemide-PVP and furosemide-inulin (1:1) were milled under cryogenic conditions. Materials were analyzed by XRD, UPLC, MS and NMR. Results Upon increasing the milling time, a significant build-up of an unidentified impurity 1, probably the main degradation product, was noticed. Cogrinding of furosemide with PVP and inulin worsened chemical stabilization of the pharmaceutical. The main degradation product formed upon cryomilling was subsequently identified as 4-chloro-5-sulfamoylanthranilic acid (CSA). Based on some theoretical considerations involving specific milling conditions, the milling intensity and an expected specific milling dose have been calculated. Results indicate that cryogenic grinding is capable to initiate mechanically induced decomposition of furosemide.Conclusions Cryogenic grinding can activate and accelerate not only structural changes (solid state amorphization) but also chemical decomposition of pharmaceuticals. A cryogenic milling device should be considered as a chemical reactor, where under favourable conditions chemical reactions could be mechanically initiated

Introduction to the French GEOTRACES North Atlantic Transect (GA01): GEOVIDE cruise

The GEOVIDE cruise, a collaborative project within the framework of the international GEOTRACES programme, was conducted along the French-led section in the North Atlantic Ocean (Section GA01), between 15 May and 30 June 2014. In this special issue (https://www.biogeosciences.net/special_issue900.html), results from GEOVIDE, including physical oceanography and trace element and isotope cyclings, are presented among 18 articles. Here, the scientific context, project objectives, and scientific strategy of GEOVIDE are provided, along with an overview of the main results from the articles published in the special issue