Collagen fibril organization in the pregnant endometrium of decorin-deficient mice

In the pregnant mouse endometrium, collagen fibrillogenesis is characterized by the presence of very thick collagen fibrils which are topographically located exclusively within the decidualized stroma. This dynamic biological process is in part regulated by the small leucine-rich proteoglycans decorin and biglycan. In the present study we utilized wild-type (Dcn+/+) and decorin-deficient (Dcn-/-) time-pregnant mice to investigate the evolution of non-decidualized and decidualized collagen matrix in the uterine wall of these animals. Ultrastructural and morphometric analyses revealed that the organization of collagen fibrils in the pregnant endometrium of both non-decidualized and decidualized stroma showed a great variability of shape and size, regardless of the genotype. However, the decidualized endometrium from Dcn-/- mice contained fibrils with larger diameter and more irregular contours as compared to the wild-type littermates. In the Dcn-/- animals, the proportion of thin (10-50 nm) fibrils was also higher as compared to Dcn+/+ animals. On day 7 of pregnancy, biglycan was similarly localized in the decidualized endometrium in both genotypes. Lumican immunostaining was intense both in decidualized and non-decidualized stroma from Dcn-/- animals. The present results support previous findings suggesting that decorin participates in uterine collagen fibrillogenesis. In addition, we suggest that the absence of decorin disturbs the process of lateral assembly of thin fibrils, resulting in very thick collagen fibrils with irregular profiles. Our data further suggest that decorin, biglycan and lumican might play an interactive role in collagen fibrillogenesis in the mouse endometrium, a process modulated according to the stage of pregnancy.

Maternal diabetes affects specific extracellular matrix components during placentation

During embryo implantation, invasive trophoblast cells mediate embryo invasion into the decidualized stroma, forming a rich network of lacunae that connect the embryonic tissues to the maternal blood vessels. Placentation is probably guided by the composition and organization of the endometrial extracellular matrix. Certain pathological conditions that occur during pregnancy, including diabetes, have been linked to abnormal placental morphology and consequent fetal morbidity. We used immunoperoxidase techniques to identify members of the collagen, proteoglycan and glycoprotein families in the various compartments of the rat placenta and to determine whether experimentally induced diabetes affects placental morphology and alters the distribution of these molecules during pregnancy. Single injections of alloxan (40 mg kg(-1) i.v.) were used to induce diabetes on day 2 of pregnancy in Wistar rats. Placentas were collected on days 14, 17, and 20. Type I and III collagen, as well as the proteoglycans decorin and biglycan, were found to be distributed throughout the placentas of control and diabetic rats. In both groups, laminin expression decreased at the end of pregnancy. In contrast, fibronectin was detected in the labyrinth region of diabetic rats at all gestational stages studied, whereas it was detected only at term pregnancy in the placentas of control rats. These results show for the first time that some extracellular matrix molecules are modulated during placental development. However, as diabetic rats presented increased fibronectin deposition exclusively in the labyrinth region, we speculate that diabetes alters the microenvironment at the maternal-fetal interface, leading to developmental abnormalities in the offspring.

Adherence and invasion of Bacteroidales isolated from the human intestinal tract

Members of the genera Bacteroides and Parabacteroides are important constituents of both human and animal intestinal microbiota, and are significant facultative pathogens. In this study, the ability of Bacteroides spp. and Parabacteroides distasonis isolated from both diarrhoeal and normal stools (n = 114) to adhere to and invade HEp-2 cells was evaluated. The presence of putative virulence factors such as capsule and fimbriae was also investigated. Adherence to HEp-2 cells was observed in 75.4% of the strains, which displayed non-localized clusters. Invasion was observed in 37.5% and 26% of the strains isolated from diarrhoeal and non-diarrhoeal stools, respectively. All strains displayed a capsule, whereas none of them showed fimbriae-like structures. This is the first report of the ability of Bacteroides spp. and P. distasonis to adhere to and invade cultured HEp-2 epithelial cells.

Characterisation of anthracyclines from a cosmomycin D-producing species of Streptomyces by collisionally-activated dissociation and ion mobility mass spectrometry

Cultures of cosmomycin D-producing Streptomyces olindensis ICB20 that were propagated for many generations underwent mutations that resulted in production of a range of related anthracyclines by the bacteria. The anthracyclines that retained the two trisaccharide chains of the parent compound were separated by HPLC. Exact mass determination of these compounds revealed that they differed from cosmomycin D (CosD) in that they contained one to three fewer oxygen atoms (loss of hydroxyl groups). Some of the anthracyclines that were separated by HPLC had the same mass. The location from which the hydroxyl groups had been lost relative to CosD (on the aglycone and/or on the sugar residues) was probed by collisionally-activated dissociation using an electrospray ionisation linear quadrupole ion trap mass spectrometer. The presence of anthracyclines with the same mass, but different structure, was confirmed using an electrospray ionisation travelling wave ion mobility mass spectrometer.

Serine-like proteolytic enzymes correlated with differential pathogenicity in patients with acute Acanthamoeba keratitis

P>Acute ocular infection due to free-living amoebae of the genus Acanthamoeba is characterized by severe pain, loss of corneal transparency and, eventually, blindness. Proteolytic enzymes secreted by trophozoites of virulent Acanthamoeba strains have an essential role in the mechanisms of pathogenesis, including adhesion, invasion and destruction of the corneal stroma. In this study, we analysed the relationship between the extracellular proteases secreted by clinical isolates of Acanthamoeba and the clinical manifestations and severity of disease that they caused. Clinical isolates were obtained from patients who showed typical symptoms of Acanthamoeba keratitis. Trophozoites were cultivated axenically, and extracellular proteins were collected from cell culture supernatants. Secreted enzymes were partially characterized by gelatin and collagen zymography. Acanthamoeba trophozoites secreted proteases with different molecular masses, proteolysis rates and substrate specificities, mostly serine-like proteases. Different enzymatic patterns of collagenases were observed, varying between single and multiple collagenolytic activities. Low molecular weight serine proteases were secreted by trophozoites associated with worse clinical manifestations. Consequently, proteolytic enzymes of some Acanthamoeba trophozoites could be related to the degree of their virulence and clinical manifestations of disease in the human cornea.

Inconclusive results in conventional serological screening for Chagas` disease in blood banks: evaluation of cellular and humoral response

To find the most reliable screening method for Trypanosoma cruzi infection in blood banks. Epidemiological data, lymphoproliferation assay, parasitological, conventional serological tests: immunofluorescence, haemagglutination, ELISA with epimastigote and trypomastigote antigens and reference serological tests: trypomastigote excreted-secreted antigens (TESA) blot and chemiluminescent ELISA assay with mucine from trypomastigote forms were applied to individuals with inconclusive serology, non-chagasic individuals and chronic chagasic patients. TESA blot had the best performance when used as a single test in all the groups. In the inconclusive group 20.5% of individuals were positive for TESA blot, 23.3% for either lymphoproliferation or TESA blot, and 17.8% for lymphoproliferation only. Positive lymphoproliferation without detectable antibodies was observed in 5.47% of all inconclusive serology cases. Analysis of six parameters (three serological assays, at least one parasitological test, one lymphoproliferation assay and epidemiological data) in the inconclusive group showed that diagnosis of Chagas` disease was probable in 15 patients who were positive by two or more serological tests or for whom three of those six parameters were positive. TESA blot is a good confirmatory test for Chagas` disease in the inconclusive group. Although lymphoproliferation suggests the diagnosis of Chagas` disease in the absence of antibodies when associated with a high epidemiological risk of acquiring Chagas` disease, the data from this study and the characteristics of the lymphoproliferation assay (which is both laborious and time-consuming) do not support its use as a confirmatory test in blood-bank screening. However, our findings underscore the need to develop alternative methods that are not based on antibody detection to improve the diagnosis when serological tests are inconclusive.

Spastic Paraplegia, Optic Atrophy, and Neuropathy: New Observations, Locus Refinement, and Exclusion of Candidate Genes

SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by our group in a large inbred Brazilian family with 25 affected individuals. This condition is clinically defined by: 1. congenital optic atrophy; 2. progressive spastic paraplegia with onset in infancy; and 3. progressive motor and sensory axonal neuropathy. Overall, we are now aware of 68 SPOAN patients (45 females and 23 males, with age ranging from 5 to 72 years), 44 of which are presented here for the first time. They were all born in the same geographic micro region. Those 68 patients belong to 43 sibships, 40 of which exhibit parental consanguinity. Sixty-one patients were fully clinically evaluated and 64 were included in the genetic investigation. All molecularly studied patients are homozygotes for D11S1889 at 11q13. This enabled us to reduce the critical region for the SPOAN gene from 4.8 to 2.3 Mb, with a maximum two point lod score of 33.2 (with marker D11S987) and of 27.0 (with marker D11S1889). Three genes located in this newly defined critical region were sequenced, but no pathogenic mutation was detected. The gene responsible for SPOAN remains elusive.

Hypotheses Testing on a Multivariate Null Intercept Errors-in-Variables Model

Considering the Wald, score, and likelihood ratio asymptotic test statistics, we analyze a multivariate null intercept errors-in-variables regression model, where the explanatory and the response variables are subject to measurement errors, and a possible structure of dependency between the measurements taken within the same individual are incorporated, representing a longitudinal structure. This model was proposed by Aoki et al. (2003b) and analyzed under the bayesian approach. In this article, considering the classical approach, we analyze asymptotic test statistics and present a simulation study to compare the behavior of the three test statistics for different sample sizes, parameter values and nominal levels of the test. Also, closed form expressions for the score function and the Fisher information matrix are presented. We consider two real numerical illustrations, the odontological data set from Hadgu and Koch (1999), and a quality control data set.

Three-dimensional description and mathematical characterization of the parasellar internal carotid artery in human infants

Inside the `cavernous sinus` or `parasellar region` the human internal carotid artery takes the shape of a siphon that is twisted and torqued in three dimensions and surrounded by a network of veins. The parasellar section of the internal carotid artery is of broad biological and medical interest, as its peculiar shape is associated with temperature regulation in the brain and correlated with the occurrence of vascular pathologies. The present study aims to provide anatomical descriptions and objective mathematical characterizations of the shape of the parasellar section of the internal carotid artery in human infants and its modifications during ontogeny. Three-dimensional (3D) computer models of the parasellar section of the internal carotid artery of infants were generated with a state-of-the-art 3D reconstruction method and analysed using both traditional morphometric methods and novel mathematical algorithms. We show that four constant, demarcated bends can be described along the infant parasellar section of the internal carotid artery, and we provide measurements of their angles. We further provide calculations of the curvature and torsion energy, and the total complexity of the 3D skeleton of the parasellar section of the internal carotid artery, and compare the complexity of this in infants and adults. Finally, we examine the relationship between shape parameters of the parasellar section of the internal carotid artery in infants, and the occurrence of intima cushions, and evaluate the reliability of subjective angle measurements for characterizing the complexity of the parasellar section of the internal carotid artery in infants. The results can serve as objective reference data for comparative studies and for medical imaging diagnostics. They also form the basis for a new hypothesis that explains the mechanisms responsible for the ontogenetic transformation in the shape of the parasellar section of the internal carotid artery.

Efficient solutions to factored MDPs with imprecise transition probabilities

When modeling real-world decision-theoretic planning problems in the Markov Decision Process (MDP) framework, it is often impossible to obtain a completely accurate estimate of transition probabilities. For example, natural uncertainty arises in the transition specification due to elicitation of MOP transition models from an expert or estimation from data, or non-stationary transition distributions arising from insufficient state knowledge. In the interest of obtaining the most robust policy under transition uncertainty, the Markov Decision Process with Imprecise Transition Probabilities (MDP-IPs) has been introduced to model such scenarios. Unfortunately, while various solution algorithms exist for MDP-IPs, they often require external calls to optimization routines and thus can be extremely time-consuming in practice. To address this deficiency, we introduce the factored MDP-IP and propose efficient dynamic programming methods to exploit its structure. Noting that the key computational bottleneck in the solution of factored MDP-IPs is the need to repeatedly solve nonlinear constrained optimization problems, we show how to target approximation techniques to drastically reduce the computational overhead of the nonlinear solver while producing bounded, approximately optimal solutions. Our results show up to two orders of magnitude speedup in comparison to traditional ""flat"" dynamic programming approaches and up to an order of magnitude speedup over the extension of factored MDP approximate value iteration techniques to MDP-IPs while producing the lowest error of any approximation algorithm evaluated. (C) 2011 Elsevier B.V. All rights reserved.

Symmetry breaking in the genetic code: Finite groups

We investigate the possibility of interpreting the degeneracy of the genetic code, i.e., the feature that different codons (base triplets) of DNA are transcribed into the same amino acid, as the result of a symmetry breaking process, in the context of finite groups. In the first part of this paper, we give the complete list of all codon representations (64-dimensional irreducible representations) of simple finite groups and their satellites (central extensions and extensions by outer automorphisms). In the second part, we analyze the branching rules for the codon representations found in the first part by computational methods, using a software package for computational group theory. The final result is a complete classification of the possible schemes, based on finite simple groups, that reproduce the multiplet structure of the genetic code. (C) 2010 Elsevier Ltd. All rights reserved.

The gas-phase alcoholysis of protonated homoleptic alkoxysilanes

Tetra-alkoxysilanes are common and useful reagents in sol-gel processes and understanding their reactivity is important in the design of new materials. The mechanism of gas-phase reactions that mimic alcoholyis of Si(OMe)(4) (usually known as TMOS) under acidic conditions have been studied by Fourier transform ion cyclotron resonance techniques and density functional calculations at the B3LYP/6-311+G(d,p) level. The proton affinity of TMOS has been estimated at 836.4 kJ mol(-1) and protonation of TMOS gives rise to an ionic species that is best represented as trimethoxysilyl cations associated with a methanol molecule. Protonated TMOS undergoes rapid and sequential substitution of the methoxy groups in the gas-phase upon reaction with alcohols. The calculated energy profile of the reaction indicates that the substitution reaction through an S(N)2 type mechanism may be more favorable than frontal attack at silicon. Furthermore, the sequential substitution reactions are promoted by a mechanism that involves proton shuttle from the most favorable protonation site to the oxygen of the departing group mediated by the neutral reagent molecule.

Structure of chemically prepared poly-(para-phenylenediamine) investigated by spectroscopic techniques

The structure of chemically prepared poly-p-phenylenediamine (PpPD) was investigated by Resonance Raman (RR), FTIR, UV-VIS-NIR, X-ray photoelectron (XPS), X-ray Absorption at Nitrogen K edge (N K XANES), and Electron paramagnetic Resonance (EPR) spectroscopies. XPS, EPR and N K XANES data reveal that polymeric structure is formed mainly by radical cations and dication nitrogens. It excludes the possibility that PpPD chains have azo or phenazinic nitrogens, as commonly is supposed in the literature. The RR spectrum of PpPD shows two characteristic bands at 1527 cm(-1) and 1590 cm(-1) that were assigned to nu C=N and nu C=C of dication units, respectively, similar to polyaniline in pernigraniline base form. The presence of radical cations was confirmed by Raman data owing to the presence of bands at 1325/1370 cm(-1), characteristic of nu C-N of polaronic segments. Thus, all results indicate that PpPD has a doped PANT-like structure, with semi-quinoid and quinoid rings, and has no phenazinic rings, as observed for poly-o-phenylenediamine. (C) 2009 Elsevier Ltd. All rights reserved.

Processens inverkan på den dragna stångens rakhet samt dragskivans slitage

Examensarbetets syfte var att undersöka vilka parametrar som har störst inverkan på rakheten i processen dragen stång, med avseende på kortvågighet samt vilka faktorer som har störst inverkan på dragskivans slitage. Materialet som undersöktes var OVAKO 803 D som är en storvolymsprodukt, 6 stycken trådringar testades varav 3st var valsad tråd och resterande 3 st skalsvarvade. Parametrar som undersöktes var dragkonans vinkel, bärningens längd och övergångsradien mellan dessa. Statistisk försöksplanering med fullständigt faktorförsök har använts.

Are empathy and compassion bad for the professional social worker?

Recent studies have shown that social workers and other professional helpers who work with traumatized individuals run a risk of developing compassion fatigue or secondary traumatic stress. Some researchers have hypothesized that helpers do this as a result of feeling too much empathy or too much compassion for their clients, thereby implying that empathy and compassion may be bad for the professional social worker. This paper investigates these hypotheses. Based on a review of current research about empathy and compassion it is argued that these states are not the causes of compassion fatigue. Hence, it is argued that empathy and compassion are not bad for the professional social worker in the sense that too much of one or the other will lead to compassion fatigue.