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Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Actinobacteria have proven themselves as the major producers of bioactive compounds with wide applications. In this study, 35 actinobacteria strains were isolated from soil samples collected from the Himalayan mountains region in Pakistan. The isolated strains were identified by polyphasic taxonomy and were prioritized based on biological and chemical screening to identify the strains with ability to produce inimitable metabolites. The biological screening included antimicrobial activity against Staphylococcus aureus, Micrococcus luteus, Salmonella enterica, Escherichia coli, Mycobacterium aurum, and Bacillus subtilis and anticancer activity using human cancer cell lines PC3 and A549. For chemical screening, methanolic extracts were investigated using TLC, HPLC-UV/MS. The actinobacteria strain PU-MM93 was selected for scale-up fermentation based on its unique chemical profile and cytotoxicity (50–60% growth inhibition) against PC3 and A549 cell lines. The scale-up fermentation of PU-MM93, followed by purification and structure elucidation of compounds revealed this strain as a promising producer of the cytotoxic anthracycline aranciamycin and aglycone SM-173-B along with the potent neuroprotective carboxamide oxachelin C. Other interesting metabolites produced include taurocholic acid as first report herein from microbial origin, pactamycate and cyclo(L-Pro-L-Leu). The study suggested exploring more bioactive microorganisms from the untapped Himalayan region in Pakistan, which can produce commercially significant compounds. [ABSTRACT FROM AUTHOR]

Following cardiac surgical procedures, multiple drainage systems remain in place inside the patient's chest to prevent the development of pericardial effusion or pneumothorax. Therefore, postoperative bleeding must be diligently observed. Currently, observation of the exudate rate is performed through periodical visual inspection of the reservoir. To improve postoperative monitoring, a measurement system based on load cells was developed to automatically detect bleeding rates. A reservoir retaining bracket was instrumented with a load cell. The signal was digitized by a microcontroller and then processed and displayed on customized software written in LabView. In cases where bleeding rates reach critical levels, the device will automatically sound an alarm. Additionally, the bleeding rate is displayed on the screen with the status of the alarm, as well as the fluid level of the reservoir. These data are all logged to a file. The measurement system has been validated for gain stability and drift, as well as for sensor accuracy, with different in vitro examinations. Additionally, performance of the measurement device was tested in a clinical pilot study on patients recovering from cardiac surgical procedures. The in vitro investigation showed that the monitoring device had excellent gain and drift stability, as well as sensor accuracy, with a resolution of 2.6 mL/h for the bleeding rate. During the clinical examination, bleeding rates of all patients were correctly measured. Continuously recording drainage volume using the developed system was comparable to manual measurements performed every 30 min by a nurse. Implementation of continuous digital measurements could improve patient safety and reduce the workload of medical professionals working in intensive care units. [ABSTRACT FROM AUTHOR]

The transformation of ancestral phenotypes into novel traits is poorly understood for many examples of evolutionary novelty. Ancestrally, salamanders have a biphasic life cycle with an aquatic larval stage, a brief and pronounced metamorphosis, followed by a terrestrial adult stage. Repeatedly during evolution, metamorphic timing has been delayed to exploit growth-permissive environments, resulting in paedomorphic salamanders that retain larval traits as adults. We used thyroid hormone (TH) to rescue metamorphic phenotypes in paedomorphic salamanders and then identified quantitative trait loci (QTL) for life history traits that are associated with amphibian life cycle evolution: metamorphic timing and adult body size. We demonstrate that paedomorphic tiger salamanders (Ambystoma tigrinum complex) carry alleles at three moderate effect QTL (met1-3) that vary in responsiveness to TH and additively affect metamorphic timing. Salamanders that delay metamorphosis attain significantly larger body sizes as adults and met2 explains a significant portion of this variation. Thus, substitution of alleles at TH-responsive loci suggests an adaptive pleiotropic basis for two key life-history traits in amphibians: body size and metamorphic timing. Our study demonstrates a likely pathway for the evolution of novel paedomorphic species from metamorphic ancestors via selection of TH-response alleles that delay metamorphic timing and increase adult body size. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the predictive value of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting malignant transformation of plexiform neurofibromas in children with neurofibromatosis type 1 (NF1). An electronic search of the medical records was performed to determine patients with NF1 who had undergone FDG-PET for plexiform neurofibroma between 2000 and 2011. All clinical, radiologic, pathology information and operative reports were reviewed. Relationship between histologic diagnosis, radiologic features and FDG-PET maximum standardized uptake value (SUV) was evaluated. This study was approved by the Institutional Review Board of our institution. 1,450 individual patients were evaluated in our Multidisciplinary Neurofibromatosis Program, of whom 35 patients underwent FDG-PET for suspected MPNST based on change or progression of clinical symptoms, or MRI findings suggesting increased tumor size. Twenty patients had concurrent pathologic specimens from biopsy/excision of 27 distinct lesions (mean age 14.9 years). Pathologic interpretation of these specimens revealed plexiform and atypical plexiform neurofibromas ( n = 8 each), low grade MPNST ( n = 2), intermediate grade MPNST ( n = 4), high grade MPNST ( n = 2), GIST ( n = 1) and non-ossifying fibroma ( n = 1). SUV of plexiform neurofibromas (including typical and atypical) was significantly different from MPNST (2.49 (SD = 1.50) vs. 7.63 (SD = 2.96), p < 0.001). A cutoff SUV value of 4.0 had high sensitivity and specificity of 1.0 and 0.94 to distinguish between PN and MPNST. FDG-PET can be helpful in predicting malignant transformation in children with plexiform neurofibromas and determining the need for biopsy and/or surgical resection. [ABSTRACT FROM AUTHOR]

review of the literature revealed that recently published phase diagrams of the Fe-Nb system show considerable discrepancies regarding phase equilibria with the melt and the homogeneity ranges of the intermetallic phases, specifically of the Laves phase FeNb. Therefore the system has been reinvestigated by metallography, electron probe microanalysis (EPMA), and differential thermal analysis (DTA). Temperatures of invariant reactions were determined and the homogeneity ranges of the two intermetallic phases, FeNb Laves phase and FeNb μ phase, which both exist within a wide composition range, were established. [ABSTRACT FROM AUTHOR]

Background: Routine surveillance of spontaneous reporting data and subsequent disproportionality analyses have indicated that the use of vancomycin might be associated with an increased risk of hepatic events.Objective: To conduct a meta-analysis of published randomized controlled clinical trials (RCTs) to better understand if the use of vancomycin is potentially associated with an increased risk of hepatic events.Data Sources: A comprehensive search and review of published clinical studies indexed in MEDLINE, PubMed, International Pharmaceutical Abstracts and the Cochrane Library from 1950 to June 2010 was conducted.Study Selection: The inclusion criteria consisted of (i) published RCTs comparing vancomycin with/without other additional treatments to other comparators; and (ii) studies that reported hepatic events.Data Extraction: The data related to any hepatic events reported in RCTs were extracted and examined. The quality of selected studies was assessed based on the Jadad scale. The effect size was presented as a risk ratio (RR) with a 95% CI and number needed to harm. The pooled RRs were calculated by using both fixed-effects and random-effects models. The impact of publication bias was assessed by funnel plot and the Egger's test.Data Synthesis: A total of 20 RCTs, including 7419 patients, met the study inclusion criteria and were selected. An increased incidence of hepatic events, specifically elevated serum aminotransferase levels, was observed in patients receiving vancomycin, when compared with other comparators (pooled RR=1.95; 95% CI 1.62, 2.36; p<0.001), but the majority of the events were mild to moderate in nature. No evidence is currently available suggesting that the use of vancomcycin confers a risk of progressive or severe drug-induced liver injury.Conclusions: Continuous monitoring of hepatic events on a routine basis among patients with the use of vancomycin is suggested. [ABSTRACT FROM AUTHOR]

At the transition from the gas to the liquid phase of water, a wealth of new phenomena emerge, which are absent for isolated H2O molecules. Many of those are important for the existence of life, for astrophysics and atmospheric science. In particular, the response to electronic excitation changes completely as more degrees of freedom become available. Here we report the direct observation of an ultrafast transfer of energy across the hydrogen bridge in (H2O)2 (a so-called water dimer). This intermolecular coulombic decay leads to an ejection of a low-energy electron from the molecular neighbour of the initially excited molecule. We observe that this decay is faster than the proton transfer that is usually a prominent pathway in the case of electronic excitation of small water clusters and leads to dissociation of the water dimer into two H2O+ ions. As electrons of low energy (∼0.7–20 eV) have recently been found to efficiently break-up DNA constituents, the observed decay channel might contribute as a source of electrons that can cause radiation damage in biological matter. [ABSTRACT FROM AUTHOR]

Little is known about the genetic basis of sex determination in vertebrates though considerable progress has been made in recent years. In this study, segregation analysis and linkage mapping were performed to localize an amphibian sex-determining locus (ambysex) in the tiger salamander (Ambystoma) genome. Segregation of sex phenotypes (male and female) among the second generation individuals of interspecific crosses (Ambystoma mexicanum × Ambystoma tigrinum tigrinum) was consistent with Mendelian expectations, although a slight female bias was observed. Individuals from these same crosses were typed for single-nucleotide polymorphisms distributed throughout the genome to identify molecular markers for ambysex. A marker (E24C3) was identified approximately 5.9 cM from ambysex. Linkage of E24C3 to ambysex was independently validated in a second, intraspecific cross (A. mexicanum). Interestingly, ambysex locates to the tip of one of the larger linkage groups of the Ambystoma meiotic map. Considering that this location does not show reduced recombination, we speculate that the ambysex locus may have arisen quite recently, within the last few million years. Localization of ambysex sets the stage for gene identification and provides important tools for studying the effect of sex in laboratory and natural populations of this model amphibian system.Heredity (2009) 102, 542–548; doi:10.1038/hdy.2009.15; published online 4 March 2009 [ABSTRACT FROM AUTHOR]

The stability of single crystals and monolayers of Mn12 single molecule magnets under the influence of X-ray radiation and other possibly disruptive influences has been investigated by means of synchrotron radiation. Clear evidence for radiation induced sample degradation was found for both single crystals and monolayers. The comparison with spectra obtained after damaging the molecules by Ar+ sputtering, metal evaporation or water moistening indicates a possibility to distinguish between radiation damage and other external influences. The results clarify some of the previous conflicting reports on the integrity of Mn12 molecules deposited on surfaces and are linked to the investigations aiming at studies of the electronic and magnetic properties of individual Mn12 clusters. [ABSTRACT FROM AUTHOR]

The new composite material Textile Reinforced Concrete (TRC) is a promising development which may open up entirely new fields for the application of the construction material concrete. The possible more filigree structures with high quality surfaces make TRC an attractive choice for the architect and give the engineer more freedom in design. However, the use of TRC requires design rules which are currently being developed at RWTH Aachen University, Germany. In this article, recent experimental results as well as modeling techniques are described. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We used two different experimental approaches to test the hypothesis that thyroid hormone receptor (TR) variation is associated with alternate life cycles modes in ambystomatid salamanders. In the first experiment, the inheritance of TRα and TRβ genotypes was determined for metamorphic and non metamorphic offspring from backcrosses between Ambystoma mexicanum (an obligate metamorphic-failure species) and metamorphic F1 hybrids (A. mexicanum × A. tigrinum tigrinum). The segregation of TR genotype was independent of the expression of life cycle mode phenotype, and neither TR locus was linked to DNA markers that flank a major-effect locus for life cycle mode. In the second experiment, a portion of the ligand-binding domain of TRα and TRβ was cloned and sequenced for DNA samples from 14 different ambystomatid salamander populations, including obligate metamorphic, facultative metamorphic, and obligate metamorphic-failure taxa. Nucleotide sequence variation was found for both TRα and TRβ, with several nonsynonomous substitutions that presumably code for nonconservative amino acid replacements. However, no general relationship was found between TR allelic variation and life cycle mode among populations or species. These data do not implicate TRs as candidate loci involved in the current maintenance or past evolution of alternate life cycle modes in members of the tiger salamander complex. [ABSTRACT FROM AUTHOR]

Vertebrate non-retinal pigment cells are derived from neural crest (NC) cells, and several mutations have been identified in the Mexican axolotl Ambystoma mexicanum (Ambystomatidae) that affect the development of these cell lineages. In ”white” ( d) mutant axolotls, premigratory NC cells differentiate as pigment cells, yet fail to disperse, survive, or both, and this leads to a nearly complete absence of pigment cells in the skin. Previous studies revealed that d affects pigment cell development non-autonomously, and have reported differences between white and wild-type axolotls in the structure and composition of the extracellular matrix through which NC and pigment cells migrate. Here we test the correspondence of d and two candidate genes: steel and AxPG. In amniotes, Steel encodes the cytokine Steel factor (mast cell growth factor; stem cell factor; kit ligand), which is expressed along the migratory pathways of melanocyte precursors and is required by these cells for their migration and survival; mammalian Steel mutants resemble white mutant axolotls in having a deficit or complete absence of pigment cells. In contrast, AxPG encodes aPG-M/versican-like proteoglycan that may promote the migration of A. mexicanum pigment cells, and AxPGexpression is reduced in white mutant axolotls. We cloned a salamander orthologue of steel and used a partial genetic linkage map of Ambystoma to determine the genomic locations of steel, AxPG, and d. We show that the three genes map to different linkage groups, excluding steel and AxPG as candidates for d. [ABSTRACT FROM AUTHOR]

The time-dependent variability of the North Atlantic Oscillation is examined in an observational data set and several model data sets with greenhouse-gas-induced external forcings. The index of the North Atlantic Oscillation state is derived from the time series of mean latitudinal position and central pressure of the Icelandic Low and the Azores High considering the synchronous meridional shifting of the two pressure systems. While the North Atlantic Oscillation is characterized by intensive interannual variability, the low-pass filtered index time series shows a decadal component with a time scale of about 50 y within almost 120 y of observation. Since the late 1960s we observe a positive trend and a transition to a strong positive phase of the phenomenon indicative of a pre-dominantly zonal circulation over the North Atlantic. This trend occurs equally in the observations and all examined model data sets with increasing greenhouse-gas-concentration and atmosphere-ocean coupling. We find statistical evidence that the radiative forcing by increasing CO2 concentration has a significant influence on the simulated variability of the North Atlantic Oscillation on time scales of 60 y and longer, independent of the initial conditions and the model version. The seasonal response is strongest in late summer and winter. The interannual variability of the North Atlantic Oscillation states on time scales less than 10 y decreases synchronously with the positive trend of its decadal-mean state implying a stabilization of its present and future zonal state. [ABSTRACT FROM AUTHOR]

The present study was designed to test the hypothesis that in hypertrophied myocardium of patients with hypertrophic obstructive cardiomyopathy (HOCM) a reduced contractile reserve provided by frequency dependent potentiation of force of contraction contributes to the myocardial dysfunction. Myectomy was performed in 8 HOCM patients with normal systolic left ventricular function at rest. Nonfailing myocardium from the hearts of three multiorgan donors was investigated for comparison. In thin myocardial strips we measured the inotropic effects of different stimulation frequencies (0,5–3.0Hz) at different extracellular Ca2+ concentrations (1.8–16.2 mmol/l). At 1.8 mmol/l extracellular Ca2+ concentration, increasing stimulation rates had no positive inotropic effect in HOCM myocardium, whereas in nonfailing myocardium force of contraction increased up to 3 Hz. Increasing extracellular Ca2+ concentrations induced a positive force-frequency relation in HOCM with a maximum at 5.4 mmol/l Ca2+. A further increase to 16.2 mmol/l Ca2+ resulted in a negative force-frequency relation in these specimens. The time to peak tension and the time to relaxation decreased at increasing stimulation frequencies at all Ca2+ concentrations investigated. In conclusion, in hypertrophied myocardium of HOCM patients increasing stimulation frequencies failed to have a positive inotropic effect at physiological extracellular Ca2+ concentrations. The induction of a positive force-frequency relation by higher Ca2+ concentrations suggests that an abnormal cellular Ca2+ handling may play an important pathophysiological role. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether subjects with low reported relative energy intake differ from those with higher relative energy intake according to characteristics such as obesity, physical activity, and macronutrient composition of the diet.Design: Cross-sectional data from a cohort study employing a semi-quantitative food frequency questionnaire (SFFQ). To determine energy intake relative BMR the ratio of reported energy intake (EI) to BMR was used and categorized by quintiles.Setting: East German (Potsdam) cohort of the EPIC study (European Prospective Investigation into Cancer and Nutrition)Subjects: 2862 women and 2356 men taking part in the EPIC-Potsdam study from January 1st to December 31st 1995.Results: A significant declining trend could be observed for BMI, percentage of body fat, and body weight from the lower to the highest quintile of EI/BMR. BMR was slightly decreasing, whereas physical activity was slightly increasing with quintiles of EI/BMR. Absolute macronutrient intake was directly related to EI/BMR. Percent macronutrient intake indicated lower fat intake, and higher carbohydrate and protein intake in low energy reporters. Energy adjusted macronutrient intake by the residual method showed no dependencies on EI/BMR.Conclusions: Underestimation of energy intake is related to obesity and affects the relation of macronutrients in the reported diet. This implies, that the assumption of adequate ranking of subjects by a SFFQ cannot be maintained. Energy adjusted intake values according to the residual method should be employed in diet-disease risk analysis since they are found to be independent of the methodological influence of underreporting. [ABSTRACT FROM AUTHOR]

EPIC-SOFT a European dietary assessment instrument for 24-h recalls Summary Within the EPIC study (European Prospective Investigation into Cancer and Nutrition) a calibration approach is applied to compare dietary data obtained by food frequency questionnaires from 9 European countries. A software for 24-h recalls was developed as the calibration instrument by the International Agency for Research on Cancer (IARC) in collaboration with all national EPIC centers. This computer program, called EPIC-SOFT, is an interview-based dietary assessment instrument that allows one to obtain a very detailed description and quantification of foods, recipes, and supplements consumed in the course of the preceding day. Probing questions and entering consumed foods in chronological order support the respondent's memory. The standardized structure prescribes - on the food group level - possibilities of description and quantification of food items to choose from. Quantification of consumed foods is supported by the EPIC-SOFT picture book that comprises colored photographs of foods in different portion sizes. The software provides an automatic coding of food items and recipe ingredients as well as calculation of nutrient intake. EPIC-SOFT is characterized by the obtained standardization of dietary data within Europe, a large number of available foods and recipes, and a very detailed description of consumed foods. Currently, EPIC-SOFT is one of the few dietary instruments providing comparable nutritional data within Europe. Schlusselworter Ernahrungserhebung - 24-Stunden-Erinnerungsprotokoll - Software [ABSTRACT FROM AUTHOR]

Summary Differences in dietary habits and lifestyle factors associated with a high dietary intake of fruit and vegetables are discussed and used to explain the disparity between results of observational epidemiologic studies consistently showing antioxidative vitamins to exert a protective effect on chronic diseases, and intervention studies so far not confirming this association. Within the scope of the "Brandenburger Ernahrungs- und Krebsstudie", the East German contribution to the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined whether study participants using supplements on a regular basis -- minerals, vitamins, protein formulation, bran/linseed, fiber, yeast or garlic pills -- differed from those who did not report use of supplements according to selected lifestyle factors and dietary intake of vitamins, minerals, fiber, cholesterol, and fat from food. The study sample consisted of 10 522 participants (4 500 men and 6 022 women) aged 35-65 years enrolled in the cohort from January 1995 to July 1996. Regular intake of one or more supplements during the past year was reported by 32.6% of women and 25.5% of men. Vitamin supplements were used by 18.8% of the women and 15.8% of the men. Figures for minerals were 14.2% for women and 8.6% for men, respectively. Garlic pills were taken regularly by 9.7% of men and 9.3% of women. Prevalence of supplement use was generally higher in women and was more pronounced in elderly participants. The most frequently used combinations were vitamin and mineral supplements, followed by a combination of garlic and either vitamin or mineral supplements. Increased use of supplements was significantly associated with higher level of education attained, regular engagement in sporting activities, health complaints, and dietary change during the previous year. No association between use of supplements and smoking status nor elevated alcohol consumption was observed. Body mass index above 30 was... [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Ernäehrungswissenschaft is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of OR Spectrum is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Coronary artery disease causes an increase in glutamate uptake and alanine output by the heart. We assessed the effects of acute myocardial ischemia on alanine and glutamate exchange and ammonia production in 10 anesthetized open-chest domestic swine (46.9±0.7 kg). Coronary blood flow was controlled through an extracorporal perfusion circuit. After a nonischemic control period (aerobic) the blood flow in the left anterior descending coronary artery was reduced by 60%. Arterial and anterior interventricular venous samples where drawn before and during 35 min of ischemia. Subendocardial blood flow, measured using radiolabeled microspheres, decreased from 1.27±0.16 to 0.25±0.09 (ml/g)/min, and left-ventricular wall-thickening fell to 47% of aerobic values. Ischemia resulted in a significant increase in the rate of glucose uptake (p<0.05) and a switch to net lactate production (p<0.01). Ischemia did not affect the rates of alanine output (−0.9±1.0 vs. −0.3±0.3 μmol/min) or glutamate uptake (−0.4±1.1 vs. 0.3±0.6 μmol/min), but did increase the venous-arterial difference for ammonia (−4.1±4.1 to 52.7±5.5 μM, p<0.0001) and the ammonia output (−0.33±0.24 to 1.34±0.14 μmol/min, p<0.0001). In conclusion, acute ischemia did not stimulate greater alanine output or glutamate uptake. However, acute ischemia did cause an increase in anaerobic glycolysis rate and ammonia output, which reflects a profound disruption in myocardial energy metabolism. [ABSTRACT FROM AUTHOR]

Copyright of Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The facial, lateral, axial, and dorsal thermograms of 52 healthy young volunteers were studied. A high degree of asymmetry was encountered. The supra-orbital areas could be distinguished in the majority of the cases. Several distinct thermal patterns matching the vascular anatomy were found to exist. An intra-cranial tumour cannot be detected on the basis of asymmetry but only from disturbance of the thermographic patterns. [ABSTRACT FROM AUTHOR]

A 51-year-old man presented with a 1-year history of polyneuropathy necessitating the use of a wheelchair. Initial diagnosis was idiopathic chronic inflammatory demyelinating polyneuropathy (CIDP) and associated monoclonal gammopathy. Investigations for multiple myeloma, including bone marrow aspiration and biopsy, were negative. What was initially felt to be an incidental osteosclerotic focus noted on the radiographic bone survey was eventually shown to be a solitary osteosclereotic plasmacytoma with associated amyloid. This dramatically altered treatment. This case emphasizes the importance of including osteosclerotic plasmacytoma in the differential diagnosis of a focal sclerotic bone lesion in the clinical setting of polyneuropathy. These lesions are less likely to progress to multiple myeloma than lytic plasma cell neoplasms, and the presence of polyneuropathy often results in earlier diagnosis and treatment with enhanced prospect of cure. The finding of amyloid deposition within the osteosclerotic lesion may be of prognostic importance. [ABSTRACT FROM AUTHOR]

Tissue regeneration is associated with complex changes in gene expression and post-translational modifications of proteins, including transcription factors and histones that comprise chromatin. We tested 172 compounds designed to target epigenetic mechanisms in an axolotl (Ambystoma mexicanum) embryo tail regeneration assay. A relatively large number of compounds (N = 55) inhibited tail regeneration, including 18 histone deacetylase inhibitors (HDACi). In particular, romidepsin, an FDA-approved anticancer drug, potently inhibited tail regeneration when embryos were treated continuously for 7 days. Additional experiments revealed that romidepsin acted within a very narrow, post-injury window. Romidepsin treatment for only 1-minute post amputation inhibited regeneration through the first 7 days, however after this time, regeneration commenced with variable outgrowth of tailfin tissue and abnormal patterning. Microarray analysis showed that romidepsin altered early, transcriptional responses at 3 and 6-hour post-amputation, especially targeting genes that are implicated in tumor cell death, as well as genes that function in the regulation of transcription, cell differentiation, cell proliferation, pattern specification, and tissue morphogenesis. Our results show that HDAC activity is required at the time of tail amputation to regulate the initial transcriptional response to injury and regeneration. [ABSTRACT FROM AUTHOR]

Vertebrates exhibit substantial diversity in genome size, and some of the largest genomes exist in species that uniquely inform diverse areas of basic and biomedical research. For example, the salamander Ambystoma mexicanum (the Mexican axolotl) is a model organism for studies of regeneration, development and genome evolution, yet its genome is ~10× larger than the human genome. As part of a hierarchical approach toward improving genome resources for the species, we generated 600 Gb of shotgun sequence data and developed methods for sequencing individual laser-captured chromosomes. Based on these data, we estimate that the A. mexicanum genome is ~32 Gb. Notably, as much as 19 Gb of the A. mexicanum genome can potentially be considered single copy, which presumably reflects the evolutionary diversification of mobile elements that accumulated during an ancient episode of genome expansion. Chromosome-targeted sequencing permitted the development of assemblies within the constraints of modern computational platforms, allowed us to place 2062 genes on the two smallest A. mexicanum chromosomes and resolves key events in the history of vertebrate genome evolution. Our analyses show that the capture and sequencing of individual chromosomes is likely to provide valuable information for the systematic sequencing, assembly and scaffolding of large genomes. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to several articles on pulmonary toxicity published on the previous issue of the journal.