Differential Diel Translation of Transcripts With Roles in the Transfer and Utilization of Iron-Sulfur Clusters in Arabidopsis

Iron-sulfur (Fe-S) clusters are evolutionarily ancient ubiquitous protein cofactors which have mostly catalytic functions but can also have structural roles. In Arabidopsis thaliana, we presently know a total of 124 Fe-S metalloproteins that are encoded in the genome. Fe-S clusters are highly sensitive to oxidation. Therefore, we hypothesized that Fe-S cluster protein biogenesis is adjusted following the daily rhythms in metabolism driven by photosynthesis at the whole-plant, organ, cellular and sub-cellular levels. It had been concluded previously that little such regulation occurs at the transcript level among the genes functioning in Fe-S cluster assembly. As an initial step toward testing our hypothesis, we thus addressed the diel time course of the translation state of relevant transcripts based on publicly available genome-wide microarray data. This analysis can answer whether the translation of the pool of transcripts of a given gene is temporarily either enhanced or suppressed, and when during the day. Thirty-three percent of the transcripts with functions in Fe-S cluster assembly exhibited significant changes in translation state over a diurnal time course, compared to 26% of all detected transcripts. These transcripts comprised functions in all three steps of cluster assembly including persulfide formation, Fe-S cluster formation and Fe-S cluster transfer to target apoproteins. The number of Fe-S cluster carrier/transfer functions contributed more than half of these transcripts, which reached maxima in translation state either during the night or the end of the night. Similarly, translation state of mitochondrial frataxin and ferredoxin, which are thought to contribute Fe and electrons during cluster formation, peaked during the night. By contrast, translation state of chloroplast SUFE2 in persulfide formation and cytosolic Fe-S cluster formation scaffold protein NBP35 reached maxima in translation state during the day. Among the transcripts encoding target Fe-S cluster-utilizing proteins, 19% exhibited diurnal variation in translation state. Day-time maxima of translation state were most common among these transcripts, with none of the maxima during the night (ZT18). We conclude that diurnal regulation of translation state is important in metalloprotein biogenesis. Future models of Fe-S protein biogenesis require more comprehensive data and will have to accommodate diurnal dynamics

Analysis of red chalk drawings from the workshop of Giovanni Battista Piranesi using fiber optics reflectance spectroscopy

The viability of fiber optics reflectance spectroscopy (FORS) for the differentiation of red chalk drawing media was investigated, focusing on the group of drawings from the workshop of Giovanni Battista Piranesi (1720–1778) at the Staatliche Kunsthalle Karlsruhe, Germany. The evaluation of spectra was supported by principal component analysis (PCA). The method was tested on mock-up drawings made with recently acquired natural and synthetic red chalks of known origin. It was possible to sort these mock-up drawings according to chalk type and application technique. The compositional differences of these reference chalks were confirmed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Subsequent FORS analysis of selected original drawings revealed the existence of several closely grouped clusters, implying similarities on the basis of the underlying spectral features among the historical red chalks used in Rome. These similarities distinguished the historical drawings from the red chalk mock-up drawings, except for the drawings made with red chalk samples from the area near the town of Theley, Germany, which were shown to bear close similarities to those in the cluster of historical samples

Between-species differences in gene copy number are enriched among functions critical for adaptive evolution in Arabidopsis halleri

Complete dataset expanded from Additional file 3. (XLS 16282 kb

Epidemiological trends in mortality, event rates and case fatality of acute myocardial infarction from 2004 to 2015: results from the KORA MI registry

AIM: This study examines epidemiological trends of acute myocardial infarction (AMI) in Germany from 2004–2015 across different age groups, using data of the population-based KORA myocardial infarction registry. METHODS: Annual age-standardised, age-group- and sex-specific mortality and event rates (incident and recurrent) per 100,000 population as well as 28-day case fatality were calculated from all registered cases of AMI and coronary heart disease deaths in 25–74-year-olds from 2004–2015 and 75–84-year-olds from 2009–2015. Average annual percentage changes (AAPC) were calculated by joinpoint regression. RESULTS: Mortality rates declined considerably among the elderly (75–84 years), in men by –6.0% annually, due to declines of case fatality by –3.0% and incidence rate by 3.4% and in women by –10.0%, driven by declines in incidence (–9.1%) and recurrence rate (–4.9%). Significant mortality declines also occurred in males, 65–74 years of age (AAPC –3.8%). Among the age groups 25–54 years and 55–64 years, there was no substantial decline in mortality, event rates or case fatality except for a decline of incidence rate in 55–64-year-old men (AAPC –1.8%). CONCLUSION: Inhomogeneous AMI trends across age-groups indicate progress in prevention and treatment for the population >64 years, while among <55-year-olds, we found no significant trend in AMI morbidity and mortality. KEY MESSAGES: Age standardised AMI mortality continued to decline from 2009 to 2015 in the study region. Declines in AMI mortality were driven by declines in event rates (both incidence and recurrence rates) and case fatality. AMI trends were inconsistent across different age groups with the strongest declines in mortality and event rates among the elderly population (75–84 years of age)

Toll-like receptor 4 in experimental kidney transplantation: early mediator of endogenous danger signals

The role of toll-like receptors (TLRs) has been described in the pathogenesis of renal ischemia/reperfusion injury, but data on the expression and function of TLR4 during renal allograft damage are still scarce. We analyzed the expression of TLR4 in an experimental rat model 6 and 28 days after allogeneic kidney transplantation in comparison to control rats and rats after syngeneic transplantation. On day 6, a significant induction in TLR4 expression - restricted to the glomerular compartment - was found in acute rejecting allografts only. TLR4 expression strongly correlated with renal function, and TLR4 induction was accompanied by a significant increase in CC chemokine expression within the graft as well as in urinary CC chemokine excretion. TLR4 induction may be caused by an influx of macrophages as well as TLR4-expressing intrinsic renal cells. Fibrinogen deposition in renal allografts correlated with renal TLR4 expression and may act as a potent stimulator of chemokine release via TLR4 activation. This study provides, for the first time, data about the precise intrarenal localization and TLR4 induction after experimental kidney transplantation. It supports the hypothesis that local TLR4 activation by endogenous ligands may be one pathological link from unspecific primary allograft damage to subsequent chemokine release, infiltration and activation of immune cells leading to deterioration of renal function and induction of renal fibrosis. Copyright (c) 2012 S. Karger AG, Base

Transcriptome sequencing identifies SPL7-regulated copper acquisition genes FRO4/FRO5 and the copper dependence of iron homeostasis in Arabidopsis

24 Pags., 9 Figs., 2 Tabls., with Supplemental Data (15 Figs., 3 Tabls., 1 Method, 1 Data Set).The transition metal copper (Cu) is essential for all living organisms but is toxic when present in excess. To identify Cu deficiency responses comprehensively, we conducted genome-wide sequencing-based transcript profiling of Arabidopsis thaliana wild-type plants and of a mutant defective in the gene encoding SQUAMOSA PROMOTER BINDING PROTEIN-LIKE7 (SPL7), which acts as a transcriptional regulator of Cu deficiency responses. In response to Cu deficiency, FERRIC REDUCTASE OXIDASE5 (FRO5) and FRO4 transcript levels increased strongly, in an SPL7-dependent manner. Biochemical assays and confocal imaging of a Cu-specific fluorophore showed that high-affinity root Cu uptake requires prior FRO5/FRO4-dependent Cu(II)-specific reduction to Cu(I) and SPL7 function. Plant iron (Fe) deficiency markers were activated in Cu-deficient media, in which reduced growth of the spl7 mutant was partially rescued by Fe supplementation. Cultivation in Cu-deficient media caused a defect in root-to-shoot Fe translocation, which was exacerbated in spl7 and associated with a lack of ferroxidase activity. This is consistent with a possible role for a multicopper oxidase in Arabidopsis Fe homeostasis, as previously described in yeast, humans, and green algae. These insights into root Cu uptake and the interaction between Cu and Fe homeostasis will advance plant nutrition, crop breeding, and biogeochemical research.We acknowledge postdoctoral fellowships to M.B. from the Alexander von Humboldt Foundation and the Spanish Ministry of Science and Innovation; a Deutsche Forschungsgemeinshaft Heisenberg fellowship and funding from the FRONTIERS program at the University of Heidelberg, Germany, and the European Union InP Public Health Impact of Long-Term, Low-Level Mixed Element Exposure in Susceptible Population Strata (FOOD-CT-2006-016253) to U.K.; a grant from the National Science Foundation (IOS-0919739) to E.L.C.; a postdoctoral fellowship from the Spanish Foundation of Science and Technology (MEC-FECYT) to D.C.; National Institutes of Health Grant GM42143 to S.S.M.; and support from the University of California, Los Angeles–Department of Energy Institute for Genomics and Proteomics under Contract DE-FC02-02ER63421 to M.P.Peer reviewe

Nephron-specific expression of components of the renin–angiotensin–aldosterone system in the mouse kidney

Introduction: The renin–angiotensin–aldosterone system (RAAS) plays an integral role in the regulation of blood pressure, electrolyte and fluid homeostasis in mammals. The capability of the different nephron segments to form components of the RAAS is only partially known. This study therefore aimed to characterize the nephron-specific expression of RAAS components within the mouse kidney. Materials and methods: Defined nephron segments of adult C57B/16 mice were microdissected after collagenase digestion. The gene expression of renin, angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin II receptors 1a (AT1a), 1b (AT1b), and 2 (AT2) was assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Results: Renin mRNA was present in glomeruli, in proximal tubules, in distal convoluted tubules (DCT) and cortical collecting ducts (CCD). AGT mRNA was found in proximal tubules, descending thin limb of Henle’s loop (dTL) and in the medullary part of the thick ascending limb (mTAL). ACE mRNA was not detectable in microdissected mouse nephron segments. AT1a, AT1b and AT2 mRNA was detected in glomeruli and proximal convoluted tubules. Conclusions: Our data demonstrate a nephron-specific distribution of RAAS components. All components of the local RAAS – except ACE – are present in proximal convoluted tubules, emphasizing their involvement in sodium and water handling

Renal function during rofecoxib therapy in patients with metastatic cancer: retrospective analysis of a prospective phase II trial

German Clinical Trials Register DRKS: DRKS0000011