988 research outputs found
The complete nucleotide sequences of the five genetically distinct plastid genomes of Oenothera, subsection Oenothera: I. Sequence evaluation and plastome evolution†
The flowering plant genus Oenothera is uniquely suited for studying molecular mechanisms of speciation. It assembles an intriguing combination of genetic features, including permanent translocation heterozygosity, biparental transmission of plastids, and a general interfertility of well-defined species. This allows an exchange of plastids and nuclei between species often resulting in plastome–genome incompatibility. For evaluation of its molecular determinants we present the complete nucleotide sequences of the five basic, genetically distinguishable plastid chromosomes of subsection Oenothera (=Euoenothera) of the genus, which are associated in distinct combinations with six basic genomes. Sizes of the chromosomes range from 163 365 bp (plastome IV) to 165 728 bp (plastome I), display between 96.3% and 98.6% sequence similarity and encode a total of 113 unique genes. Plastome diversification is caused by an abundance of nucleotide substitutions, small insertions, deletions and repetitions. The five plastomes deviate from the general ancestral design of plastid chromosomes of vascular plants by a subsection-specific 56 kb inversion within the large single-copy segment. This inversion disrupted operon structures and predates the divergence of the subsection presumably 1 My ago. Phylogenetic relationships suggest plastomes I–III in one clade, while plastome IV appears to be closest to the common ancestor
Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report
BACKGROUND: Genetic changes in the LIM homeobox transcription factor 1 beta (LMX1B) have been associated with focal segmental glomerulosclerosis (FSGS) without the extra-renal or ultrastructural manifestations of Nail-patella syndrome (NPS) known as Nail-patella-like renal disease (NPLRD). Fabry disease (FD) is an X-linked lysosomal disease caused by the deficiency of alpha-galactosidase A. The classic form of the disease is characterized by acroparesthesia, angiokeratomas, cornea verticillata, hypertrophic cardiomyopathy, strokes, and chronic kidney disease. Podocyte myelin bodies on ultrastructural examination of kidney tissue are very characteristic of FD; however some medications and other conditions may mimic this finding. CASE PRESENTATION: Here, we report on a female patient with chronic kidney disease (CKD), positive family history for kidney disease and kidney biopsy showing a FSGS lesion and presence of focal myelin figures within podocytes concerning for FD. However, genetic testing for FD was negative. After comprehensive clinical, biochemical, and genetic evaluation, including whole exome and RNA sequencing, she was ultimately diagnosed with NPLRD. CONCLUSIONS: This case illustrates the difficulties of diagnosing atypical forms of rare Mendelian kidney diseases and the role of a multidisciplinary team in an individualized medicine clinic setting in combination with state-of-the-art sequencing technologies to reach a definitive diagnosis
Simulation of Claylike Colloids
We investigate properties of dense suspensions and sediments of small
spherical silt particles by means of a combined Molecular Dynamics (MD) and
Stochastic Rotation Dynamics (SRD) simulation. We include van der Waals and
effective electrostatic interactions between the colloidal particles, as well
as Brownian motion and hydrodynamic interactions which are calculated in the
SRD-part. We present the simulation technique and first results. We have
measured velocity distributions, diffusion coefficients, sedimentation
velocity, spatial correlation functions and we have explored the phase diagram
depending on the parameters of the potentials and on the volume fraction.Comment: 20 pages, 14 figure
The Complete Nucleotide Sequences of the 5 Genetically Distinct Plastid Genomes of Oenothera, Subsection Oenothera: II. A Microevolutionary View Using Bioinformatics and Formal Genetic Data
A unique combination of genetic features and a rich stock of information make the flowering plant genus Oenothera an appealing model to explore the molecular basis of speciation processes including nucleus–organelle coevolution. From representative species, we have recently reported complete nucleotide sequences of the 5 basic and genetically distinguishable plastid chromosomes of subsection Oenothera (I–V). In nature, Oenothera plastid genomes are associated with 6 distinct, either homozygous or heterozygous, diploid nuclear genotypes of the 3 basic genomes A, B, or C. Artificially produced plastome–genome combinations that do not occur naturally often display interspecific plastome–genome incompatibility (PGI). In this study, we compare formal genetic data available from all 30 plastome–genome combinations with sequence differences between the plastomes to uncover potential determinants for interspecific PGI. Consistent with an active role in speciation, a remarkable number of genes have high Ka/Ks ratios. Different from the Solanacean cybrid model Atropa/tobacco, RNA editing seems not to be relevant for PGIs in Oenothera. However, predominantly sequence polymorphisms in intergenic segments are proposed as possible sources for PGI. A single locus, the bidirectional promoter region between psbB and clpP, is suggested to contribute to compartmental PGI in the interspecific AB hybrid containing plastome I (AB-I), consistent with its perturbed photosystem II activity
final results of a noninterventional study
Background Data are limited regarding routine use of everolimus after initial
vascular endothelial growth factor (VEGF)–targeted therapy. The aim of this
prospective, noninterventional, observational study was to assess efficacy and
safety of everolimus after initial VEGF-targeted treatment in patients with
metastatic renal cell carcinoma (mRCC) in routine clinical settings. Methods
Everolimus was administered per routine clinical practice. Patients with mRCC
of any histology from 116 active sites in Germany were included. The main
objective was to determine everolimus efficacy in time to progression (TTP).
Progression-free survival (PFS), treatment duration, tumor response, adherence
to everolimus regimen, treatment after everolimus, and safety were also
assessed. Results In the total population (N = 334), median follow-up was 5.2
months (range, 0–32 months). Median treatment duration (safety population, n =
318) was 6.5 months (95% confidence interval [CI], 5–8 months). Median TTP and
median PFS were similar in populations investigated. In patients who received
everolimus as second-line treatment (n = 211), median (95% CI) TTP was 7.1
months (5–9 months) and median PFS was 6.9 months (5–9 months). Commonly
reported adverse events (safety population, n = 318) were dyspnea (17%),
anemia (15%), and fatigue (12%). Limitations of the noninterventional design
should be considered. Conclusions This study reflects routine clinical use of
everolimus in a large sample of patients with mRCC. Favorable efficacy and
safety were seen for everolimus after previous therapy with one VEGF-targeted
agent. Results of this study confirm everolimus as one of the standard options
in second-line therapy for patients with mRCC. Novartis study code,
CRAD001LD27: VFA registry for noninterventional studies
(http://www.vfa.de/de/forschung/nisdb/ webcite)
Everolimus in metastatic renal cell carcinoma after failure of initial anti-VEGF therapy: final results of a noninterventional study
Background: Data are limited regarding routine use of everolimus after initial vascular endothelial growth factor (VEGF)-targeted therapy. The aim of this prospective, noninterventional, observational study was to assess efficacy and safety of everolimus after initial VEGF-targeted treatment in patients with metastatic renal cell carcinoma (mRCC) in routine clinical settings. Methods: Everolimus was administered per routine clinical practice. Patients with mRCC of any histology from 116 active sites in Germany were included. The main objective was to determine everolimus efficacy in time to progression (TTP). Progression-free survival (PFS), treatment duration, tumor response, adherence to everolimus regimen, treatment after everolimus, and safety were also assessed. Results: In the total population (N = 334),median follow-up was 5.2 months (range, 0-32 months). Median treatment duration (safety population, n = 318) was 6.5 months (95% confidence interval [CI], 5-8 months). Median TTP and median PFS were similar in populations investigated. In patients who received everolimus as second-line treatment (n = 211),median (95% CI) TTP was 7.1 months (5-9 months) and median PFS was 6.9 months (5-9 months). Commonly reported adverse events (safety population, n = 318) were dyspnea (17%),anemia (15%), and fatigue (12%). Limitations of the noninterventional design should be considered. Conclusions: This study reflects routine clinical use of everolimus in a large sample of patients with mRCC. Favorable efficacy and safety were seen for everolimus after previous therapy with one VEGF-targeted agent. Results of this study confirm everolimus as one of the standard options in second-line therapy for patients with mRCC
Effect of dehydration, produced by mercupurin, on the plasma volume of normal persons
1. 1. Plasma volume, serum protein concentration, hematocrit value, arterial and venous blood pressures, and body weight were determined in ten normal subjects before, and twenty-four hours after, the injection of 2 c.c. of mercupurin.2. 2. There was a fall in plasma volume in every case, averaging 544 +/- 87.7 c.c., or 15.7 +/- 2.4 per cent of the control determination; an average rise in serum proteins of 0.74 +/- 0.14 Gm., or 11.5 +/- 2.6 per cent; and an average rise in hematocrit of 2.9 +/- 0.6, or 6.9 +/- 1.8 per cent.3. 3. A diuresis was experienced in every case; the mean was 1.73 +/- 0.3 kg., or 2.6 +/- 0.5 per cent of the body weight.4. 4. Associated with the diuresis and decrease in plasma volume, there was a fall in venous pressure and pulse pressure.5. 5. In some instances, the subjects exhibited weakness, apathy, dizziness, and faintness, suggesting a diminution in cardiac output.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32575/1/0000704.pd
On the Driving Mechanism of the Annual Cycle of the Florida Current Transport
The mechanisms involved in setting the annual cycle of the Florida Current transport are revisited using an adjoint model approach. Adjoint sensitivities of the Florida Current transport to wind stress reproduce a realistic seasonal cycle with an amplitude of ~1.2 Sv (1 Sv ≡ 106 m3 s−1). The annual cycle is predominantly determined by wind stress forcing and related coastal upwelling (downwelling) north of the Florida Strait along the shelf off the North American coast. Fast barotropic waves propagate these anomalies southward and reach the Florida Strait within a month, causing an amplitude of ~1 Sv. Long baroclinic planetary Rossby waves originating from the interior are responsible for an amplitude of ~0.8 Sv but have a different phase. The sensitivities corresponding to the first baroclinic mode propagate westward and are highly influenced by topography. Considerable sensitivities are only found west of the Mid-Atlantic Ridge, with maximum values at the western shelf edge. The second baroclinic mode also has an impact on the Florida Current variability, but only when a mean flow is present. A second-mode wave train propagates southwestward from the ocean bottom on the western side of the Mid-Atlantic Ridge between ~36° and 46°N and at Flemish Cap, where the mean flow interacts with topography, to the surface. Other processes such as baroclinic waves along the shelf and local forcing within the Florida Strait are of minor importance
The PANDA GEM-based TPC Prototype
We report on the development of a GEM-based TPC prototype for the PANDA
experiment. The design and requirements of this device will be illustrated,
with particular emphasis on the properties of the recently tested GEM-detector,
the characterization of the read-out electronics and the development of the
tracking software that allows to evaluate the GEM-TPC data.Comment: submitted to NIMA 4 pages, 6 picture
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