Atomic modifications by synchrotron radiation at the calcite-ethanol interface.

This article reports on studies of the chemical alterations induced by synchrotron radiation at the calcite-ethanol interface, a simple model system for interfaces between minerals and more complex organic molecules containing OH groups. A combination of X-ray reflectivity and X-ray photoelectron spectroscopy of natural calcite, cleaved in distilled ethanol to obtain new clean interfaces, indicated that, during a 5 h period, the two top atomic layers of calcite, CaCO(3), transform into calcium oxide, CaO, by releasing CO(2). Also, the occupation of the first ordered layer of ethanol attached to calcite by hydrogen bonds almost doubles. Comparison between radiated and non-radiated areas of the same samples demonstrate that these effects are induced only by radiation and not caused by aging. These observations contribute to establishing a time limit for synchrotron experiments involving fluid-mineral interfaces where the polar OH group, as present in ethanol, plays a key role in their molecular structure and bonding. Also, the chemical evolution observed in the interface provides new insight into the behavior of some complex organic molecules involved in biomineralization processes.

Molecular ordering of ethanol at the calcite surface.

To produce biominerals, such as shells, bones, and teeth, living beings create organic compounds that control the growth of the solid phase. Investigating the atomic scale behavior of individual functional groups at the mineral-fluid interface provides fundamental information that is useful for constructing accurate predictive models for natural systems. Previous investigations of the activity of coccolith-associated polysaccharides (CAP) on calcite, using atomic force microscopy (AFM) [Henriksen, K., Young, J. R., Bown, P. R., and Stipp, S. L. S. Palentology 2004, 43 (Part 3), 725-743] and molecular dynamics (MD) modeling [Yang, M., Stipp, S. L. S., and Harding, J. H. Cryst. Growth Des. 2008, 8 (11), 4066-4074], have suggested that OH functional groups control polysaccharide attachment. The purpose of this work was to characterize, using X-ray reflectivity (XR) combined with molecular dynamics (MD) simulations, the structuring on calcite of a layer of the simplest carbon chain molecule that contains an OH group, ethanol (CH(3)-CH(2)-OH). We found evidence that EtOH forms a highly ordered structure at the calcite surface, where the first layer molecules bond with calcite. The ethanol molecules stand up perpendicularly at the interface or nearly so. As a consequence, the fatty, CH(3) ends form a new surface, about 6 Å from the termination of the bulk calcite, and beyond that, there is a thin gap where ethanol density is low. Following is a more disordered layer that is two to three ethanol molecules thick, about 14 Å, where density more resembles that of bulk liquid ethanol. The good agreement between theory and experiment gives confidence that a theoretical approach can offer information about behavior in more complex systems.

[Gender reassignment surgery from male to female]. / Geschlechtsangleichung von Mann zu Frau.

For many trans*women, the surgical assignment of the male genital into a female is a fundamental part of the transition. Erogenous sensation of the neoclitoris is achieved by meticulous preparation of the penile glans with the neurovascular bundle. Several techniques are available for the formation of a neovagina, the penile inversion technique developed by Burou in the 1950s being the gold standard. With this technique, the inverted penile shaft skin is used as a pedicled flap to line the neovaginal canal. Alternatively, free skin grafts can be used, which serve primarily as a technique for redo procedures. Another technique is the use of intestinal segments to line the vaginal canal. This method is mostly used for redo procedures, but can also be performed primarily if penile skin is too small. Due to the numerous steps involved in the preparation, a wide variety of complications must be expected. Injury to the rectum during dissection of the neovaginal space, with an incidence of 4.5%, represents the greatest challenge. The most common complications are urethra-associated; hereby both a deviation of the urinary stream and strictures of the urethra are possible. The subjective satisfaction of trans*women with the surgical outcome is high and is reported in various studies to be 72-92%. On the basis of validated questionnaires it could also be shown that gender reassignment surgery leads to an increase in the trans*specific quality of life and promotes both subjectively perceived well-being and sexual satisfaction.

Sexuality after Male-to-Female Gender Affirmation Surgery.

Male-to-Female (MtF) gender affirmation surgery (GAS) comprises the creation of a functional and aesthetic perineogenital complex. This study aimed to evaluate the effect of GAS on sexuality. We retrospectively surveyed all 254 MtF transsexual patients who had undergone GAS with penile inversion vaginoplasty at the Department of Urology, University Hospital Essen, Germany, between 2004 and 2010. In total, we received 119 completed questionnaires after a median of 5.05 years since surgery. Of the study participants, 33.7% reported a heterosexual, 37.6% a lesbian, and 22.8% a bisexual orientation related to the self-perceived gender. Of those who had sexual intercourse, 55.8% rated their orgasms to be more intensive than before, with 20.8% who felt no difference. Most patients were satisfied with the sensitivity of the neoclitoris (73.9%) and with the depth of the neovaginal canal (67.1%). The self-estimated pleasure of sexual activity correlated significantly with neoclitoral sensitivity but not with neovaginal depth. There was a significant correlation between the ease with which patients were able to become sexually aroused and their ability to achieve orgasms. In conclusion, orgasms after surgery were experienced more intensely than before in the majority of women in our cohort and neoclitoral sensitivity seems to contribute to enjoyment of sexual activity to a greater extent than neovaginal depth.

Publisher Correction: Interactions of the Calcite {10.4} Surface with Organic Compounds: Structure and Behaviour at Mineral - Organic Interfaces.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Activation of extracellular regulated kinases (ERK1/2) but not AKT predicts poor prognosis in colorectal carcinoma and is associated with k-ras mutations.

Signal transduction and modulation represent central mechanisms in cellular processes such as cell-cycle regulation, oncogenesis, and apoptosis. The aim of this study was to determine the prognostic relevance of two kinases important in the regulation of cell proliferation and apoptosis in 135 colorectal cancer cases: AKT and extracellular regulated kinases (ERK1/2). We investigated the relationship of phospho-ERK1/2 (pERK1/2) and phospho-AKT (pAKT) with associated parameters (EGFR, COX-2, cyclin-D1), proliferative activity (Ki-67), and apoptosis (TUNEL) using immunohistochemistry. Additionally, the k-ras gene was screened for mutations to determine its putative association with ERK1/2 activation. Activation of ERK1/2 but not AKT correlated statistically with the presence of k-ras mutations (P = 0.015). Survival analysis of phospho-ERK1/2 immunoexpression showed a significant correlation with decreased overall survival (OS). The multivariate Cox regression analysis identified pERK1/2 as an independent prognostic parameter (P = 0.005). Activation of ERK1/2 in colorectal cancer may indicate aggressive tumor behavior and may constitute an independent prognostic factor. Furthermore, our data suggest that mutations of the k-ras oncogene may induce activation of ERK1/2. We propose immunohistochemical determination of pERK1/2 status as a promising candidate for the identification of high-risk patients who would benefit from new anticancer drugs targeting the ERK pathway.

Interactions of the Calcite {10.4} Surface with Organic Compounds: Structure and Behaviour at Mineral - Organic Interfaces.

The structure and the strength of organic compound adsorption on mineral surfaces are of interest for a number of industrial and environmental applications, oil recovery, CO2 storage and contamination remediation. Biomineralised calcite plays an essential role in the function of many organisms that control crystal growth with organic macromolecules. Carbonate rocks, composed almost exclusively of calcite, host drinking water aquifers and oil reservoirs. In this study, we examined the ordering behaviour of several organic compounds and the thickness of the adsorbed layers formed on calcite {10.4} surfaces. We used X-ray reflectivity (XRR) to study calcite {10.4} surfaces that were prepared in three alcohols: methanol, isopropanol and pentanol and one carboxylic acid: octanoic acid. All molecules adsorbed in self-assembled layers, where thickness depended on the density and the length of the molecule. For methanol and isopropanol, molecular dynamic simulations (MD) provided complementary information, which allowed us to develop a surface model. Branching in isopropanol induced slightly less ordering because of the additional degree of freedom. Pentanol and octanoic acid adsorbed as single monolayers. The results of this work indicate that adhered organic compounds from the surrounding environment can affect the surface behaviour, depending on properties of the organic compound.

Systematic review: microscopic colitis.

BACKGROUND: Collagenous and lymphocytic colitis are fairly common causes of chronic non-bloody diarrhoea, especially in elderly female. AIM: To present a systematic review of microscopic colitis. METHODS: A PubMed search using the MeSH terms microscopic colitis, collagenous colitis, lymphocytic colitis and chronic diarrhoea was performed. RESULTS: Annual incidence of each disorder is 4-6/100,000 inhabitants. The aetiology is unknown. Clinical characteristics are well described and there is an association with autoimmune diseases. Budesonide is the best-documented short-term treatment of collagenous colitis. In meta-analysis pooled odds ratio for clinical response after 6-8 weeks of treatment was 12.3 (95% CI: 5.5-27.5) in comparison with placebo. The evidence for bismuth subsalicylate is weaker and the effectiveness of other alternatives such as loperamide, cholestyramine, aminosalicylates, probiotics, or Boswellia serrata extract is unknown. Although unproven, in unresponsive severe disease azathioprine or methotrexate may be tried. No controlled trials have been carried out in lymphocytic colitis. The long-term prognosis of microscopic colitis is good, serious complications are rare and there is no increased mortality. CONCLUSIONS: Clinical and epidemiological aspects of microscopic colitis are well described. Budesonide is the best-documented short-term therapy in collagenous colitis, but the optimal long-term strategy needs further study. Controlled treatment data of lymphocytic colitis are awaited for.

Overexpression of cyclo-oxygenase-2 is an independent predictor of unfavourable outcome in node-negative breast cancer, but is not associated with protein kinase B (Akt) and mitogen-activated protein kinase (ERK1/2, p38) activation or with Her-2/neu signalling pathways.

BACKGROUND AND AIM: The production of prostaglandins is regulated by cyclo-oxygenases (COXs), which also have a role in tumour development and progression in various malignancies, including breast cancer. The mechanisms by which COX-2 contributes to unfavourable prognosis are still poorly understood. The association between expression of COX-2 and possible linked signalling pathways-namely, Akt, extracellular regulated kinases (ERK1/2), the stress-activated kinase p38 or Her-2/neu-is assessed in a series of 113 node-negative breast cancers. RESULTS: COX-2 was identified as an independent prognostic factor (p = 0.034) in node-negative breast cancer by survival analysis. The lack of a relationship between COX-2 expression and activated Akt, Erk1/2, p38 and Her-2/neu was indicated by statistical analysis. CONCLUSIONS: The prognostic effect of COX-2 expression on lymph node-negative breast cancer is confirmed-COX-2 is probably not regulated by HER-2, Akt, Erk1/2 or p38. Further studies are necessary for the elucidation of the signalling pathways responsible for the modification of COX-2 expression and the increased aggressiveness of breast cancers overexpressing COX-2.

Protein structures from distance inequalities.

A computer method for folding protein backbones from distance inequalities is presented. It involves an algorithm that uses a novel approach for handling inequalities through the minimization of a continuous energy function. Tests of the folding algorithm have been carried out on a small protein, the 6PTI (bovine pancreatic trypsin inhibitor) with 56 amino acid residues, and on a medium-size protein, the 1TRM (rat trypsin) with 223 amino acid residues. Reconstructions based on a real-valued distance matrix led to folded three-dimensional structures with root-mean-square values of 0.04 A when compared with the crystallographic data. The obtained root-mean-square measures were of the order of 1 A, when distance inequalities were used for the reconstruction. Subsequently, the folding approach has been applied to distance inequalities predicted by neural network techniques that use the amino acid sequence as the only input. The inaccuracy in the inequalities predicted by the neural network was the reason for the root-mean-square value of 5.2 A. An error analysis of the method for reconstruction was performed and showed that no more than 3% inaccurate distance inequalities could be corrected for. Finally, a simple technique for root-mean-square comparisons of different protein structures is discussed.

Relationship between protein structure and geometrical constraints.

We evaluate to what extent the structure of proteins can be deduced from incomplete knowledge of disulfide bridges, surface assignments, secondary structure assignments, and additional distance constraints. A cost function taking such constraints into account was used to obtain protein structures using a simple minimization algorithm. For small proteins, the approximate structure could be obtained using one additional distance constraint for each amino acid in the protein. We also studied the effect of using predicted secondary structure and surface assignments. The constraints used in this approach typically may be obtained from low-resolution experimental data. When using a cost function based on distances, half of the resulting structures will be mirrored, because the resulting structure and its mirror image will have the same cost. The secondary structure assignments were therefore divided into chirality constraints and distance constraints. Here we report that the problem of mirrored structures, in some cases, can be solved by using a chirality term in the cost function.

A novel approach to prediction of the 3-dimensional structures of protein backbones by neural networks.

Three-dimensional structures of protein backbones have been predicted using neural networks. A feed forward neural network was trained on a class of functionally, but not structurally, homologous proteins, using backpropagation learning. The network generated tertiary structure information in the form of binary distance constraints for the C(alpha) atoms in the protein backbone. The binary distance between two C(alpha) atoms was 0 if the distance between them was less than a certain threshold distance, and 1 otherwise. The distance constraints predicted by the trained neural network were utilized to generate a folded conformation of the protein backbone, using a steepest descent minimization approach.

Protein secondary structure and homology by neural networks. The alpha-helices in rhodopsin.

Neural networks provide a basis for semiempirical studies of pattern matching between the primary and secondary structures of proteins. Networks of the perceptron class have been trained to classify the amino-acid residues into two categories for each of three types of secondary feature: alpha-helix or not, beta-sheet or not, and random coil or not. The explicit prediction for the helices in rhodopsin is compared with both electron microscopy results and those of the Chou-Fasman method. A new measure of homology between proteins is provided by the network approach, which thereby leads to quantification of the differences between the primary structures of proteins.

Analysis of the secondary structure of the human immunodeficiency virus (HIV) proteins p17, gp120, and gp41 by computer modeling based on neural network methods.

A neural network computer program, trained to predict secondary structure of proteins by exposing it to matching sets of primary and secondary structures from a database, was used to analyze the human immunodeficiency virus (HIV) proteins p17, gp120, and gp41 from their amino acid sequences. The results are compared to those obtained by the Chou-Fasman analysis. Two alpha-helical sequences corresponding to the putative fusigenic domain and to the transmembrane domain of gp41 could be predicted, as well as a possible binding site between p17 and gp41. On the basis of the secondary structure predictions, a three-dimensional model of p17 was constructed. This model was found to represent a stable conformation by an analysis using an energy-minimization program. The model predicts that p17 is attached to the membrane only by the acylated N-terminus, in analogy with the N-terminus of the gag protein of other retroviruses and also with the src oncogene protein p60src. The intracellular C-terminal part of gp41 may act as a receptor by electrostatic interaction with p17.

Serum Procollagen III Propeptide Is Not of Diagnostic Predictive Value in Collagenous Colitis.

SUMMARY: : The thickened collagen layer found subepithelially in colorectal biopsies from patients with collagenous colitis consists partly of collagen type III. Procollagen III propeptide (P-III-NP) is a product of collagen III metabolism. We analyzed serum levels of this propeptide to assess its diagnostic value in collagenous colitis. Serum from 38 patients with collagenous colitis and 38 age- and sex-matched controls were analyzed for P-III-NP. Data on the patients included duration and severity of symptoms, treatment, and thickness of the collagen layer. There was no significant difference between P-III-NP in patients (3.8 ± 2.0 µg/L) and controls (3.7 ± 1.3 µg/L), and P-III-NP did not correlate with clinical activity. There was a significant correlation, however, between P-III-NP and age both in patients (r = 0.57, p = 0.0009) and controls (r = 0.64, p = 0.0001). This study shows that P-III-NP is not useful as a diagnostic or prognostic tool in collagenous colitis, and a colonoscopy with biopsy is still the only diagnostic method available. Key Words: Collagenous colitis-Procollagen III propeptide-P-III-NP.

Antineutrophil Cytoplasmic Antibodies in Inflammatory Bowel Disease and Collagenous Colitis: No Association with Lactoferrin, ß-Glucuronidase, Myeloperoxidase, or Proteinase 3.

: Perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) occur frequently in ulcerative colitis (UC) but not in Crohn's disease (CD). Their pathogenetic importance is unknown, and studies of associated antigens have been inconsistent. Indirect immunofluorescence technique was used to screen the occurrence of antineutrophil cytoplasmic antibodies in 36 patients with UC, in 37 patients with CD, in 38 patients with collagenous colitis (CC), and in 190 controls. Enzyme immunoassays (EIAs) were used to detect the target antigen(s) by using lactoferrin (Lf), ß-glucuronidase (ß-Glc), myeloperoxidase (MPO), and proteinase 3 (PR3) as the substrates. P-ANCA was found in 23 (63.9%) of 36 of the patients with UC, in two (5.4%) of 37 with CD, in four (10.5%) of 38 with CC, and in four (2.1%) of 190 of healthy controls. No case of cytoplasmic staining pattern (C-ANCA) was found. With EIA, P-ANCA in IBD or CC was not found to be associated with reactivity to Lf, ß-Glc, MPO, or PR3, which confirms findings reported by others. P-ANCA was found in a higher frequency in UC than in CD or CC. The antigens of P-ANCA remain unidentified.

Protein folding and wring resonances.

The polypeptide chain of a protein is shown to obey topological constraints which enable long range excitations in the form of wring modes of the protein backbone. Wring modes of proteins of specific lengths can therefore resonate with molecular modes present in the cell. It is suggested that protein folding takes place when the amplitude of a wring excitation becomes so large that it is energetically favorable to bend the protein backbone. The condition under which such structural transformations can occur is found, and it is shown that both cold and hot denaturation (the unfolding of proteins) are natural consequences of the suggested wring mode model. Native (folded) proteins are found to possess an intrinsic standing wring mode.

Collagenous and lymphocytic colitis: a clinical and histopathological review.

Collagenous colitis and lymphocytic colitis are newly described colitides that are only diagnosable microscopically; therefore, both are known under the umbrella term 'microscopic colitis'. This is a short review of the clinical findings, and epidemiological and basic observations of these relatively little described colitides belonging to the group of inflammatory bowel diseases.

Veterinary school admission interviews, part 2: survey of North American schools.

A study of veterinary school admission interview practices across the USA and Canada was conducted in 1999. All 31 schools responded. INTERVIEW USE: Eighty-four percent of the veterinary schools interview applicants. Veterinary schools are more likely to interview resident than non-resident applicants (62% interviewed >or=49% of their resident applicants, while 77% interviewed or=77%). The five most common characteristics and skills the veterinary admission interview is intended to assess are communication skills, maturity, motivation for and interest in veterinary medicine, interpersonal skills, and knowledge of the veterinary profession (>or=92%). The least common characteristic or skill the veterinary admission interview is intended to assess is academic performance (23%). INTERVIEW FORMAT: Veterinary schools are most likely to offer one interview to a candidate (83%). A panel interview with between two and three interviewers is the predominant format employed (92%). The interview is of 20-45 minutes duration (88%), most commonly 30 minutes (50%). Interview questions most often address experiences in veterinary medicine, general background, and strengths and weaknesses (>or=85%). The level of interview structure is low to moderate (73%). The cold or blind interview (where interviewers are denied access to all or part of the written application) is employed by 50% of the interviewing veterinary schools. INTERVIEWERS: Interviewing veterinary schools assign interviewing to faculty veterinarians (100%). Some level of interviewer training is usually provided (87%); the most common mode of training is distribution of printed material (86%). SUMMARY AND RECOMMENDATIONS: The veterinary admissions interview is similar to that employed by schools of medicine, optometry, and dentistry, with the exception that veterinary schools are more likely to use panel interviews, to fix the interview weight in selection decisions, and to employ a cold or blind interview (these differences provide an opportunity to increase interview reliability and validity). Interview reliability and validity can be further improved by increasing interviewer training and interview structure, ensuring that the interview's format is consistent with its purpose, and identifying behavioral characteristics that are consistent with successful practice.

[The clinical consequence of blood culture results]. / Den kliniske konsekvens af bloddyrkningssvar.

The effect of blood culture results on patient management in a department of internal medicine was analyzed retrospectively. In a series of 300 patients 538 blood cultures were taken. Fifty-four (10%) of blood cultures from 44 of the 300 patients were positive, but in 16 patients cultures yielded organisms considered to be contaminants. Only 28 (9.3%) patients' cultures showed growth of clinically significant pathogenic bacteria. Antimicrobial chemotherapy was instituted in 234 (78%) patients before culture results were available. For only 21 (7%) patients did the result of the blood culture have any therapeutic consequences. The high frequency and lack of impact of negative blood cultures demands a more appropriate protocol for blood culturing, and guidelines are suggested.