From acute injury to chronic disease: pathophysiological hypothesis of an epithelial/mesenchymal crosstalk alteration in CKD

Observational clinical studies link acute kidney injury to chronic kidney disease (CKD) progression. The pathophysiological mechanisms that underlie this process are currently unknown but recently published papers suggest that tubular epithelial cells and interstitial mesenchymal cells emerge as a single unit, and their integrity alteration as a whole might lead to renal fibrosis and CKD. The present article reviews the biological findings supporting the hypothesis of an altered epithelial/mesenchymal crosstalk in fibrosis development and progression toward CK

Phylogenetic relationships in the southern African genus Drosanthemum (Ruschioideae, Aizoaceae)

Background. Drosanthemum, the only genus of the tribe Drosanthemeae, is widespread over the Greater Cape Floristic Region in southern Africa. With 114 recognized species, Drosanthemum together with the highly succulent and species-rich tribe Ruschieae constitute the 'core ruschioids' in Aizoaceae. Within Drosanthemum, nine subgenera have been described based on flower and fruit morphology. Their phylogenetic relationships, however, have not yet been investigated, hampering understanding of monophyletic entities and patterns of geographic distribution. Methods. Using chloroplast and nuclear DNA sequence data, we performed network- and tree-based phylogenetic analyses of 73 species of Drosanthemum with multiple accessions for widespread species. A well-curated, geo-referenced occurrence data set comprising the 134 genetically analysed and 863 further accessions was used to describe the distributional ranges of intrageneric lineages and the genus as a whole. Results. Phylogenetic inference supports nine clades within Drosanthemum, seven of which group in two major clades, while the remaining two show ambiguous affinities. The nine clades are generally congruent to previously described subgenera within Drosanthemum, with exceptions such as (pseudo-) cryptic species. In-depth analyses of sequence patterns in each gene region were used to reveal phylogenetic affinities inside the retrieved clades in more detail. We observe a complex distribution pattern including widespread, species-rich clades expanding into arid habitats of the interior (subgenera Drosanthemum p.p., Vespertina, Xamera) that are genetically and morphologically diverse. In contrast, less species-rich, genetically less divergent, and morphologically unique lineages are restricted to the central Cape region and more mesic conditions (Decidua, Necopina, Ossicula, Quastea, Quadrata, Speciosa). Our results suggest that the main lineages arose from an initial rapid radiation, with subsequent diversification in some clades.Raw data, code, analysis output, and species occurrence The zip file contains a ReadMe file and 4 folders: 1_main_data_and_results (the files used to produce the figures in the main text); 2_ML_phylogenetics (raw data, code, and analysis output of ML phylogenetic analyses); 3_MJ_networks (raw data [SNP/sequence motive recoded DNA alignment matrices], and output of median-joining network analyses)

The performance of irradiated CMS silicon mirco-strip detector modules

The central tracking system of the Compact Muon Solenoid (CMS) experiment will be entirely buil in silicon technology. The majority of the CMS tracker consists of silicon micro-strip detectors which have to be operated in the harsh environment of the Large Hadron Collider (LHC) over a period of ten years. The expected equivalent fluences range from a low of 0.7 x 10^14 n_1MeV/cm^2 at the outermost layers of the tracker, to a high of 1.6 x 10^14 n_1MeV/cm^2 at the layers closest to the interaction region. In this paper, results from studies of irradiatied CMS silicon detector modules are presented

Photometric determination of the mass accretion rates of pre-main sequence stars. II. NGC346 in the Small Magellanic Cloud

[Abridged] We have studied the properties of the stellar populations in the field of the NGC346 cluster in the Small Magellanic Cloud, using a novel self-consistent method that allows us to reliably identify pre-main sequence (PMS) objects actively undergoing mass accretion, regardless of their age. The method does not require spectroscopy and combines broad-band V and I photometry with narrow-band Halpha imaging to identify all stars with excess Halpha emission and derive the accretion luminosity Lacc and mass accretion rate Macc for all of them. The application of this method to existing HST/ACS photometry of the NGC346 field has allowed us to identify and study 680 bona-fide PMS stars with masses from ~0.4 to ~4 Msolar and ages in the range from ~1 to ~30 Myr. This is the first study to reveal that, besides a young population of PMS stars (~ 1 Myr old), in this field there is also an older population of PMS objects with a median age of ~20 Myr. We provide for all of them accurate physical parameters. We study the evolution of the mass accretion rate as a function of stellar parameters and find that logMacc ~ -0.6 Log t + Log m + c, where t is the age of the star, m its mass and c a quantity that is higher at lower metallicity. The high mass accretion rates that we find suggest that a considerable fraction of the stellar mass is accreted during the PMS phase and that PMS evolutionary models that do not account for this effect will systematically underestimate the true age when compared with the observations.Comment: Accepted for publication in the ApJ. 14 pages, 11 figures. Corrected typos and reference

Large-scale identification of genetic design strategies using local search

In the past decade, computational methods have been shown to be well suited to unraveling the complex web of metabolic reactions in biological systems. Methods based on flux–balance analysis (FBA) and bi-level optimization have been used to great effect in aiding metabolic engineering. These methods predict the result of genetic manipulations and allow for the best set of manipulations to be found computationally. Bi-level FBA is, however, limited in applicability because the required computational time and resources scale poorly as the size of the metabolic system and the number of genetic manipulations increase. To overcome these limitations, we have developed Genetic Design through Local Search (GDLS), a scalable, heuristic, algorithmic method that employs an approach based on local search with multiple search paths, which results in effective, low-complexity search of the space of genetic manipulations. Thus, GDLS is able to find genetic designs with greater in silico production of desired metabolites than can feasibly be found using a globally optimal search and performs favorably in comparison with heuristic searches based on evolutionary algorithms and simulated annealing

Photometric determination of the mass accretion rates of pre-main sequence stars. I. Method and application to the SN1987A field

We have developed and successfully tested a new self-consistent method to reliably identify pre-main sequence (PMS) objects actively undergoing mass accretion in a resolved stellar population, regardless of their age. The method does not require spectroscopy and combines broad-band V and I photometry with narrow-band Halpha imaging to: (1) identify all stars with excess Halpha emission; (2) derive their Halpha luminosity L(Halpha); (3) estimate the Halpha emission equivalent width; (4) derive the accretion luminosity L_acc from L(Halpha); and finally (5) obtain the mass accretion rate M_acc from L_acc and the stellar parameters (mass and radius). By selecting stars with photometric accuracy in Halpha better than 15%, the statistical uncertainty on the derived M_acc is typically <17% and is dictated by the precision of the Halpha photometry. Systematic uncertainties, of up to a factor of 3 on the value of M_acc, are caused by our incomplete understanding of the physics of the accretion process and affect all determinations of the mass accretion rate, including those based on a spectroscopic Halpha line analysis. As an application of our method, we study a field of 9.16 arcmin2 around SN1987A, using existing HST photometry. We identify as bona-fide PMS stars a total of 133 objects with a Halpha excess above the 4 sigma level and a median age of 13.5 Myr. Their median mass accretion rate of 2.6x10-8 Msolar/yr is in excellent agreement with previous determinations based on the U-band excess of the stars in this field, and with the value measured for G-type PMS stars in the Milky Way. Their L_acc shows a strong dependence on their distance from a group of hot massive stars in the field and suggests that the UV radiation of the latter is rapidly eroding the circumstellar discs around PMS stars.Comment: 18 pages, 18 figures, accepted for publication in the Astrophysical Journa

Differential Retinoic Acid Signaling in Tumors of Long- and Short-term Glioblastoma Survivors

Although the prognosis of most glioblastoma patients is poor, 3%-5% patients show long-term survival of 36 months or longer after diagnosis. To study the differences in activation of biochemical pathways, we performed mRNA and protein expression analyses of primary glioblastoma tissues from 11 long-term survivors (LTS; overall survival ≥ 36 months) and 12 short-term survivors (STS; overall survival ≤ 6 months). The mRNA expression ratio of the retinoic acid transporters fatty acid-binding protein 5 (FABP5) and cellular retinoic acid-binding protein 2 (CRABP2), which regulate the differential delivery of retinoic acid to either antioncogenic retinoic acid receptors or prooncogenic nuclear receptor peroxisome proliferator-activated receptor delta, was statistically significantly higher in the tumor tissues of STS than those of LTS (median ratio in STS tumors = 3.64, 10th-90th percentile = 1.43-4.54 vs median ratio in LTS tumors = 1.42, 10th-90th percentile = −0.98 to 2.59; P < .001). High FABP5 protein expression in STS tumors was associated with highly proliferating tumor cells and activation of 3-phosphoinositide-dependent protein kinase-1 and v-akt murine thymoma viral oncogene homolog. The data suggest that retinoic acid signaling activates different targets in glioblastomas from LTS and STS. All statistical tests were two-side