TSP1 and MMP9 genetic variants in sporadic prostate cancer

Angiogenesis plays an important role in the initiation and progression of many malignancies including prostate cancer (PCa). Therefore, genes implicated in angiogenic pathways could be susceptibility candidate genes for this malignancy. In this respect, we investigated the impact of functional genetic variants of TSP1 (N700S) and MMP9 (-1562 C/T) genes on the development and progression of PCa. This case-control study included 101 PCa patients and 106 healthy controls analyzed by polymerase chain reaction -restriction fragment length polymorphism assay. No association was observed between any of the TSP1 genotypes and PCa risk or severity; however, subjects carrying one copy of the MMP9 T allele exhibited threefold higher risk of developing PCa (OR = 2.86; P = 0.004). Regarding prognostic value, a significant association was found between the occurrence of the MMP9 T allele and the high-grade tumor (OR = 3.21; P = 0.004) and the advanced disease (OR = 2.47; P = 0.026). We also analyzed the effect of the combined genotypes on PCa risk. The patients with two high-risk genotypes exhibited 2.8-fold higher risk of developing PCa than those with only low-risk genotypes, but the association was not statistically significant. These findings suggest that MMP9 polymorphism is an independent risk factor of PCa development and aggressiveness.     

De novo trisomy 20p of paternal origin

We report on a case of a de novo trisomy 20p in a 5-year-old boy. The patient presented with dysmorphic features, mental retardation, poor coordination, cardiac malformation, kyphosis, hypospadias, cryptorchidism, and preaxial hexadactyly. No growth delay was noticed. Standard karyotype and FISH techniques allowed the characterization of the chromosome rearrangement showing a duplication spanning almost the whole short arm of chromosome 20. Therefore the karyotype was interpreted as 46,XY,der(20)(pter --> q13.3::p11.2 --> pter). Molecular studies identified the duplication of paternal origin. This is one of the rare reports with almost pure trisomy 20p characterized at the molecular level. Its phenotype is compared to other similar cases described in the literature.     

The effect of thrombolysis on short-term improvement depends on initial stroke severity

A large number of parameters have been identified as predictors of early outcome in patients with acute ischemic stroke. In the present work we analyzed a wide range of demographic, metabolic, physiological, clinical, laboratory and neuroimaging parameters in a large population of consecutive patients with acute ischemic stroke with the aim of identifying independent predictors of the early clinical course. We used prospectively collected data from the Acute Stroke Registry and Analysis of Lausanne. All consecutive patients with ischemic stroke admitted to our stroke unit and/or intensive care unit between 1 January 2003 and 12 December 2008 within 24 h after last-well time were analyzed. Univariate and multivariate analyses were performed to identify significant associations with the National Institute of Health Stroke Scale (NIHSS) score at admission and 24 h later. We also sought any interactions between the identified predictors. Of the 1,730 consecutive patients with acute ischemic stroke who were included in the analysis, 260 (15.0%) were thrombolyzed (mostly intravenously) within the recommended time window. In multivariate analysis, the NIHSS score at 24 h after admission was associated with the NIHSS score at admission (β = 1, p < 0.001), initial glucose level (β = 0.05, p < 0.002) and thrombolytic intervention (β = −2.91, p < 0.001). There was a significant interaction between thrombolysis and the NIHSS score at admission (p < 0.001), indicating that the short-term effect of thrombolysis decreases with increasing initial stroke severity. Thrombolytic treatment, lower initial glucose level and lower initial stroke severity predict a favorable early clinical course. The short-term effect of thrombolysis appears mainly in minor and moderate strokes, and decreases with increasing initial stroke severity.     

Chemical signature of magnetotactic bacteria

There are longstanding and ongoing controversies about the abiotic or biological origin of nanocrystals of magnetite. On Earth, magnetotactic bacteria perform biomineralization of intracellular magnetite nanoparticles under a controlled pathway. These bacteria are ubiquitous in modern natural environments. However, their identification in ancient geological material remains challenging. Together with physical and mineralogical properties, the chemical composition of magnetite was proposed as a promising tracer for bacterial magnetofossil identification, but this had never been explored quantitatively and systematically for many trace elements. Here, we determine the incorporation of 34 trace elements in magnetite in both cases of abiotic aqueous precipitation and of production by the magnetotactic bacterium Magnetospirillum magneticum strain AMB-1. We show that, in biomagnetite, most elements are at least 100 times less concentrated than in abiotic magnetite and we provide a quantitative pattern of this depletion. Furthermore, we propose a previously unidentified method based on strontium and calcium incorporation to identify magnetite produced by magnetotactic bacteria in the geological record.Magnetite (Fe₃O₄) is a widespread iron oxide found in geological sedimentary deposits such as banded iron formations, carbonate platforms, or paleosols (1). It can be produced through abiotic or biotic pathways. Magnetotactic bacteria (MTB) and dissimilatory iron-reducing bacteria are known to synthetize magnetite nanoparticles (2).MTB are magnetite- or greigite (Fe₃S₄)-producing bacteria found in both freshwater and marine environments. They inhabit the oxic–anoxic transition zone under microaerophilic conditions required for their growth. Magnetite or greigite crystals are actively precipitated through biological mechanisms in intracellular organelles called magnetosomes (e.g., refs. 3 and 4). Magnetosomes are assembled in chains inside the cell (Fig. 1) and provide the microorganism with a permanent magnetic dipole. This arrangement allows the bacteria to align themselves along the Earth’s geomagnetic field and to reach the optimal position along vertical chemical gradients (5, 6). When the cell dies, magnetosomes may be deposited and trapped into sediments. Magnetite can then be fossilized if the redox conditions are appropriate (1). This mineral may thus be an indirect bacterial fossil. Magnetotactic bacteria have been proposed to represent one of the most ancient biomineralizing organisms (1, 7). Thus, the identification of fossil magnetotactic bacteria, hereafter named bacterial magnetofossils, would provide strong constraints on the evolution of life and of biomineralization over geological times.Open in a separate windowFig. 1.Transmission electron microscopy images of (A) bacteria cultivated in bottles and (B) in fermentor, (C) extracted chain of magnetosomes, (D) magnetosomes treated with SDS-Triton-phenol preparation, (E) bacterial magnetite leached with EDTA, and (F) untreated magnetosome. Extracted magnetosomes display chain structures assembled by magnetosome membranes and proteins (arrows in C). In contrast with magnetite treated with SDS-Triton-phenol (E), untreated magnetosomes show traces of organic matter (arrow in F). Once treated, magnetite from AMB-1 agglomerated, as shown in D. We also observed such agglomeration in abiotic magnetite. Magnetite did not seem to be affected by EDTA leaching.Magnetite produced by MTB shows highly controlled crystallographic structure (8). It displays narrow size distributions and is in the magnetic stable single-domain range. Magnetosome chains have remarkable magnetic properties (5, 6, 9), which have been used to identify bacterial magnetofossils in sediments. Although previous studies demonstrated that observations by electron microscopy and/or magnetic measurements could detect bacterial magnetofossils in natural samples (9–13), the chain structure is generally lost during sediment aging owing to degradation of organic matter assembling magnetosomes (9, 14). This strongly complicates the identification of the bacterial magnetofossils. Moreover, those magnetites undergo variable transformations ranging from isomorphic conversion to maghemite, all the way to crystals that just barely preserve the structural integrity (15). Thus, for bacterial magnetofossil identification in ancient rock samples reliable biosignatures surviving these modifications are still needed for distinguishing biogenic from abiotic magnetite (1, 2).Geochemical fingerprints can be used as a potential tool for identifying fossilized biominerals (2, 16). For instance, chemical purity has been suggested as a common feature of minerals produced by living organisms (2). The chemical purity of magnetite from MTB has been discussed for many years (e.g., ref. 17). Although not without controversy, it was suggested that low concentrations in minor elements observed in magnetite from Martian meteorite {"type":"entrez-protein","attrs":{"text":"ALH84001","term_id":"937293154","term_text":"ALH84001"}}ALH84001 could indicate a biological origin for magnetite (18). This interpretation was supported by abiotic formation of magnetite in the laboratory, leading to high levels of elements other than iron in the crystal products (19, 20), except if initial materials highly depleted in doping elements were used (21). However, the degree of magnetite chemical purity in these previous studies was estimated by energy dispersive x-ray spectroscopy (EDXS) coupled with transmission electron microscopy, which is usually limited to the quantification of relatively elevated elemental concentrations, typically higher than 0.1–1% (22). Moreover, EDXS analyses have been used to evaluate single-element incorporations into magnetite crystals produced by MTB (23–26). These experiments tested only high element concentrations, which may not be representative of natural conditions. A detailed measurement of the low levels of trace elements likely present in trace amounts in magnetite from MTB, together with the knowledge of the concentrations of these elements in the surrounding fluids, thus remain to be established. Indeed, rather than the low or high level of impurity in the magnetite, the important point would be to establish whether differential incorporation of elements exists between biotic and abiotic magnetites. In this work, we thus determined multielement partitioning between aqueous solution and either abiotic magnetite or magnetite from magnetosomes to provide reliable signatures of biological origin.Abiotic magnetite nanoparticles were synthetized in adapting previous work (27) by mixing Fe³⁺ and Fe²⁺ to which were added 34 trace elements at concentrations of 100 ppb of each element by weight in the solution. This magnetite chemical precipitation is related to an extensive previous literature reporting studies designed for decontamination of wastewaters (e.g., refs. 28 and 29). Our experiments were performed in a glove box to prevent Fe(II) and magnetite oxidation. Biomagnetite was produced from Magnetospirillum magneticum strain AMB-1 (ATCC700264) under two different conditions: (i) in a fermentor as described in ref. 30 and (ii) in bottles following ATCC recommendations. The initial growth media of the two experiments were different. In contrast with bottle cultures, pH and pO₂ were maintained constant in the fermentor and the medium was continuously homogenized by stirring. These contrasting conditions allow us to evaluate the variability possibly induced by the biosynthesis. In either case, the bacterial growth medium was doped with the same 34 trace elements at 100 ppb each, (i.e., at the same doping level as in the abiotic syntheses). Chains of magnetosomes were extracted from cells with a high-pressure homogenizer. Magnetosome membranes surrounding magnetite were removed using a Triton-SDS-phenol solution heated at 70 °C overnight. Magnetite nanoparticles were leached with ultrapure water and contaminant-free EDTA solution to chelate and remove any element adsorbed on mineral surface (Fig. 1). Abiotic and biotic bottle experiments were carried out in duplicate. Mineralogical characterization (i.e., size, shape, and structure) of the magnetite samples was obtained from X-ray diffraction and transmission electron microscopy (Fig. 1 and Fig. S1). The element concentrations in all experimental products were measured by high-resolution inductively coupled plasma mass spectrometry.     

Stroke initial severity and outcome relative to insurance status in a universal health care system in Switzerland

Background: Socioeconomic status is thought to have a significant influence on stroke incidence, risk factors and outcome. Its influence on acute stroke severity, stroke mechanisms, and acute recanalisation treatment is less known. Methods: Over a 4‐year period, all ischaemic stroke patients admitted within 24 h were entered prospectively in a stroke registry. Data included insurance status, demographics, risk factors, time to hospital arrival, initial stroke severity (NIHSS), etiology, use of acute treatments, short‐term outcome (modified Rankin Scale, mRS). Private insured patients (PI) were compared with basic insured patients (BI). Results: Of 1062 consecutive acute ischaemic stroke patients, 203 had PI and 859 had BI. They were 585 men and 477 women. Both populations were similar in age, cardiovascular risk factors and preventive medications. The onset to admission time, thrombolysis rate, and stroke etiology according to TOAST classification were not different between PI and BI. Mean NIHSS at admission was significantly higher for BI. Good outcome (mRS ≤ 2) at 7 days and 3 months was more frequent in PI than in BI. Conclusion: We found better outcome and lesser stroke severity on admission in patients with higher socioeconomic status in an acute stroke population. The reason for milder strokes in patients with better socioeconomic status in a universal health care system needs to be explained.