Isotropic high-resolution three-dimensional confocal micro-rotation imaging for non-adherent living cells.
Recently, micro-rotation confocal microscopy has enabled the acquisition of a sequence of micro-rotated images of nonadherent living cells obtained during a partially controlled rotation movement of the cell through the focal plane. Although we are now able to estimate the three-dimensional position of every optical section with respect to the cell frame, the reconstruction of the cell from the positioned micro-rotated images remains a last task that this paper addresses. This is not strictly an interpolation problem since a micro-rotated image is a convoluted two-dimensional map of a three-dimensional reality. It is rather a 'reconstruction from projection' problem where the term projection is associated to the PSF of the deconvolution process. Micro-rotation microscopy has a specific difficulty. It does not yield a complete coverage of the volume. In this paper, experiments illustrate the ability of the classical EM algorithm to deconvolve efficiently cell volume despite of the incomplete coverage. This cell reconstruction method is compared to a kernel-based method of interpolation, which does not take account explicitly the point-spread-function (PSF). It is also compared to the standard volume obtained from a conventional z-stack. Our results suggest that deconvolution of micro-rotation image series opens some exciting new avenues for further analysis, ultimately laying the way towards establishing an enhanced resolution 3D light microscopy.


Expression of cell-adhesion molecules in embryonic induction. I. Morphogenesis of nestling feathers.
The potential relationship of cell adhesion to embryonic induction during feather formation was examined by immunohistochemical analysis of the spatiotemporal distribution of three cell-adhesion molecules (CAMs), neural CAM (N-CAM), liver CAM (L-CAM), and neuron-glia CAM (Ng-CAM), and of substrate molecules (laminin and fibronectin) in embryonic chicken skin. The N-CAM found at sites of embryonic induction in the feather was found to be similar to brain N-CAM as judged by immuno-cross-reactivity, migratory position in PAGE, and the presence of embryonic to adult conversion. In contrast to the N-CAM found in the brain, however, only one polypeptide of Mr 140,000 was seen. N-CAM-positive dermal condensations were distributed periodically under L-CAM-positive feather placodes at those sites where basement membranes are known to be disrupted. After initiation of induction, L-CAM-positive placode cells became transiently N-CAM-positive. N-CAM was asymmetrically concentrated in the dorsal region of the feather bud, while fibronectin was concentrated in the ventral region. During feather follicle formation, N-CAM was expressed in the dermal papilla and was closely apposed to the L-CAM-positive papillar ectoderm, while the dermal papilla showed no evidence of laminin or fibronectin. The collar epithelium was both N-CAM- and L-CAM-positive. During the formation of the feather filament, N-CAM appeared periodically and asymmetrically on basilar cells located in the valleys between adjacent barb ridges. In contrast to the two primary CAMs, Ng-CAM was found only on nerves supplying the feather and the skin. These studies indicate that at each site of induction during feather morphogenesis, a general pattern is repeated in which an epithelial structure linked by L-CAM is confronted with periodically propagating condensations of cells linked by N-CAM.


Continuous production of prions after infectious particles are eliminated: implications for Alzheimer's disease.
Rat septal cells, induced to enter a terminal differentiation-like state by temperature shift, produce prion protein (PrP) levels 7x higher than their proliferative counterparts. Host PrP accumulates on the plasma membrane, newly elaborated nanotubes, and cell-to-cell junctions, important conduits for viral spread. To find if elevated PrP increased susceptibility to FU-CJD infection, we determined agent titers under both proliferating and arresting conditions. A short 5 day arrest and a prolonged 140 day arrest increased infectivity by 5x and 122x (>2 logs) respectively as compared to proliferating cells. Total PrP rapidly increased 7x and was even more elevated in proliferating cells that escaped chronic arrest conditions. Amyloid generating PrP (PrP-res), the "infectious prion" form, present at ~100,000 copies per infectious particle, also increased proportionately by 140 days. However, when these highly infectious cells were switched back to proliferative conditions for 60 days, abundant PrP-res continued to be generated even though 4 logs of titer was lost. An identical 4 log loss was found with maximal PrP and PrP-res production in parallel cells under arresting conditions. While host PrP is essential for TSE agent spread and replication, excessive production of all forms of PrP can be inappropriately perpetuated by living cells, even after the initiating infectious agent is eliminated. Host PrP changes can start as a protective innate immune response that ultimately escapes control. A subset of other neurodegenerative and amyloid diseases, including non-transmissible AD, may be initiated by environmental infectious agents that are no longer present.


CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice.
Roles for host immune response in carcinogenesis are not well defined. Recent studies have shown that microbially driven inflammation can lead to colon cancer and that prior transfer of regulatory lymphocytes expressing CD4 and CD25 prevents the innate inflammatory events that lead to colon cancer in mice. To further examine the ability of regulatory lymphocytes to inhibit carcinogenesis, 129/SvEv Rag-2-deficient mice were inoculated by gastric gavage with Helicobacter hepaticus, an enteric bacterial pathogen of mice. Mice were then treated at 1, 3, or 12 months after infection with adoptive transfer of CD4(+)CD45RB(lo)CD25(+)-regulatory cells. Mice dosed with regulatory cells at 4 or 12 weeks after H. hepaticus infection had reduced severity of inflammatory bowel disease and significantly lower risk of colon cancer during the 8 month observation period, compared with infected mice that had not received cells. This suggested that regulatory cells were able to interrupt the ongoing innate immune events in the stepwise progression to cancer. Transfer of regulatory cells into chronically infected mice with established cancer reduced severity of colitis, epithelial dysplasia, and cancer, but did not eliminate all tumors. Regulatory cells lacking anti-inflammatory cytokine interleukin (IL)-10 were unable to inhibit inflammatory bowel disease, dysplasia, or cancer, showing that IL-10 was required for the protective effects of lymphocytes in this setting. Taken together, the data suggest that IL-10-mediated suppression of host innate inflammatory response was pivotal in interrupting carcinogenesis. Regulatory lymphocytes and cytokines may have implications for novel therapies for colon cancer in humans.


Fmoc-based synthesis of peptide thioacids for azide ligations via 2-cyanoethyl thioesters.
Rapid and efficient preparation of peptide thioacids from 2-cyanoethyl peptide thioesters has been accomplished. S-2-Cyanoethyl peptide thioesters were obtained cleanly without the need for purification from resin-bound tert-butyl peptide thioesters using 3-mercaptopropionitrile as a nucleophile. Elimination of the 2-cyanoethyl group proceeded rapidly (t(1/2) < 8 min) under mild conditions and furnished peptide thioacids up to the size of a 16-mer. Peptide thioacids could be isolated or formed in situ and reacted smoothly with electron-deficient azides yielding an amide as the ligation product.


Development of a set of compensating Triticum aestivum-Dasypyrum villosum Robertsonian translocation lines.
Dasypyrum villosum (L.) Candargy, a wild relative of bread wheat ( Triticum aestivum L.), is the source of many agronomically important genes for wheat improvement. Production of compensating Robertsonian translocations (cRobTs), consisting of D. villosum chromosome arms translocated to homoeologous wheat chromosome arms, is one of the initial steps in exploiting this variation. The cRobTs for D. villosum chromosomes 1V, 4V, and 6V have been reported previously. Here we report attempted cRobTs for wheat - D. villosum chromosome combinations 2D/2V, 3D/3V, 5D/5V, and 7D/7V. The cRobTs for all D. villosum chromosomes were recovered except for the 2VS and 5VL arms. As was the case with the 6D/6V combination, no cRobTs involving 2D/2V chromosomes were recovered; instead, cRobT T2BS·2VL involving a nontargeted chromosome was recovered. All cRobTs are fertile, although the level of spike fertility and hundred kernel weight (HKW) varied among the lines. The set of cRobTs involving 12 of the 14 D. villosum chromosomes will be useful in wheat improvement programs. In fact, among the already reported cRobTs, T6AL·6VS carrying the Pm21 gene is deployed in agriculture and many useful genes have been reported on other cRobTs including resistance to stem rust race UG99 on T6AS·6VL.


Comparison of differences and determinants between presence and absence of sleep disturbance in hepatocellular carcinoma patients.
Hepatocellular carcinoma patients often experience sleep disturbance after undergoing transcatheter arterial chemoembolization (TACE). The objectives of this study were to (1) examine and compare symptom distress, depression, and sleep quality in hepatocellular carcinoma patients undergoing TACE with sleep disturbance versus without sleep disturbance and (2) examine the determinants of sleep disturbance in these patients. Hepatocellular carcinoma patients undergoing TACE were recruited. The patients were evaluated 1 week (T1) and 1 month (T2) after receiving TACE in terms of performance status, symptom distress, depression (T1), and sleep disturbance (T2). Logistic regression was used to determine the predictive factors of sleep disturbance. Patients with sleep disturbance reported significantly higher overall symptom distress and depression and lower sleep quality than patients without sleep disturbance. The 5 leading causes of symptom distress in both groups were fatigue, pain, poor appetite, chest tightness, and fever. Older age, greater symptom distress, and higher levels of depression were significantly associated with sleep disturbance. The results of this study show significant associations among symptom distress, depression at baseline, and sleep problems 1 month after undergoing TACE. Clinicians should be aware of the possibility of lasting sleep disturbance in hepatocellular carcinoma patients undergoing TACE. In clinical care, symptom management, psychological consultation, and relaxation training may promote sleep quality.


Time-to-Fatigue During Incline Treadmill Running: Implications for Individualized Training Prescription.
Uphill running has been touted as a key interval training tactic for distance runners despite few scientifically derived recommendations for individualized training prescription. To date, a majority of uphill training research has focused on shorter, faster training bouts; however, longer, slower bouts based on an individual's velocity at maximum oxygen consumption (Vmax) may prove more effective. One potential longer bout length may be associated with the time Vmax can be maintained (Tmax), an approach proven effective in level-grade interval training. Therefore, the purpose of this investigation included examining the Tmax, heart rate, and test-retest reliability of incline treadmill running (INC) on a 10% grade at 65, 70, 75, 80, and 85%Vmax compared with level-grade running at Vmax. Twelve moderately trained distance runners (age, 26.4 ± 4.8; body mass, 64.3 ± 12.9 kg; height, 171.2 ± 9.3 cm; and V̇O2max, 56.6 ± 7.6 ml·min⁻¹·kg⁻¹) completed 2 Tmax INC trials at each submaximal Vmax and a level-grade Tmax at Vmax. The dependent variables were Tmax, heart rate plateau (HR(Plateau)), and half-time to heart rate plateau (½HR(Plateau)) of each condition. Statistical significance was set to p ≤ 0.05. Student's t-test revealed no significant differences in Tmax, HR(Plateau), and ½HR(Plateau) between trials 1 and 2 at any INC condition. One-way analysis of variance revealed significant differences in (a) Tmax during INC at 75, 80, and 85%Vmax and level-grade at Vmax and (b) ½HR(Plateau) during INC at 80 and 85%Vmax and all other conditions. In conclusion, Tmax and heart rate dynamics during INC proved reliable, and simple regression analysis revealed ∼68%Vmax during INC yields the same level-grade Tmax at Vmax.


Effect of brood size manipulation on offspring physiology: an experiment with passerine birds.
The environment experienced during ontogeny has a significant impact on the physiological condition of offspring. This, in turn, forecasts survival probabilities and future reproductive potential. Despite the prominent role that the concept of condition plays in evolutionary studies, the physiological and biochemical characters that define it remain relatively unexplored. In this study, we quantified the impact of brood size manipulations on the physiology and biochemistry of nestling tree swallows (Tachycineta bicolor) shortly before they fledged. Over two breeding seasons, we either increased or decreased the number of individuals in a brood by a single nestling. Every 2-4 days, we determined the resting rate of oxygen consumption [V(O(2))] of individuals in each brood. Growth was followed until 16 days of age, at which time, to look for potential trade-offs in energy allocation, we measured total lipid mass, skeletal muscle and organ mass, indices of blood oxygen-carrying capacity and the activities of key metabolic enzymes in various tissues. Surprisingly, there was a minimal response of most characters to brood manipulation, suggesting that physiological and biochemical development is relatively invariant except perhaps under extreme conditions. Individuals reared in artificially enlarged broods, however, had a significantly lower body mass, body-size-adjusted [V(O(2))], gizzard mass and total lipid mass. These individuals also had decreased activity of cardiac 3-hydroxyacyl CoA dehydrogenase, suggesting a decreased capacity for oxidation of fatty acids. How these characters affect survival or the future adult phenotype remains unknown.


OntoGene in BioCreative II.
Research scientists and companies working in the domains of biomedicine and genomics are increasingly faced with the problem of efficiently locating, within the vast body of published scientific findings, the critical pieces of information that are needed to direct current and future research investment. In this report we describe approaches taken within the scope of the second BioCreative competition in order to solve two aspects of this problem: detection of novel protein interactions reported in scientific articles, and detection of the experimental method that was used to confirm the interaction. Our approach to the former problem is based on a high-recall protein annotation step, followed by two strict disambiguation steps. The remaining proteins are then combined according to a number of lexico-syntactic filters, which deliver high-precision results while maintaining reasonable recall. The detection of the experimental methods is tackled by a pattern matching approach, which has delivered the best results in the official BioCreative evaluation. Although the results of BioCreative clearly show that no tool is sufficiently reliable for fully automated annotations, a few of the proposed approaches (including our own) already perform at a competitive level. This makes them interesting either as standalone tools for preliminary document inspection, or as modules within an environment aimed at supporting the process of curation of biomedical literature.


Is there a role for herbal medicine in the treatment of pancreatic cancer?. Highlights from the "44th ASCO Annual Meeting". Chicago, IL, USA. May 30 - June 3, 2008.
One of the greatest challenges in the treatment of pancreatic cancer remains its inherent lack of beneficial response to cytotoxic chemotherapy. According to the encyclopedic knowledge on herbal medicine regimen and clinical experience accumulated for centuries, traditional Chinese medicine can provide new avenues for alternative treatments of pancreatic diseases. Chinese herbal extracts have been widely used for the treatment of various cancers, but objective information on their efficacy in pancreatic cancer is lacking. This article provides a summary of herbal medicine, presented at the Annual Meeting of ASCO, 2008. The clinical applications of these active compounds warrant further investigation in randomized, controlled clinical trials.


Leaf senescence is delayed in maize expressing the Agrobacterium IPT gene under the control of a novel maize senescence-enhanced promoter.
We have genetically modified maize plants to delay leaf senescence. A senescence-enhanced promoter from maize (P(SEE1)) was used to drive expression of the Agrobacterium cytokinin biosynthesis gene IPT in senescing leaf tissue. Three maize lines expressing IPT from P(SEE1), Sg1, Sg2 and Sg3, were analysed in detail, representing mild, intermediate and extreme expression, respectively, of the delayed-senescence phenotype. Backcross populations segregating for the presence or absence of the P(SEE1Xba)IPTNOS transgene also simultaneously segregated for the senescence phenotype. At the time of ear leaf emergence, individuals of lines Sg1 and Sg2 segregating for the presence of the transgene carried about three fewer senescing leaves than control (transgene-minus) segregants, and IPT transcript levels were higher in leaves at incipient senescence than in young leaves. Leaves of transgenic Sg3 plants were significantly greener than controls and progressed directly from fully green to bleached and dead without an intervening yellowing phase. IPT transcript abundance in this line was not related to the initiation of senescence. Extended greenness was accompanied by a delay in the loss of photosynthetic capacity with leaf age. The delayed-senescence trait was associated with relatively minor changes in morphology and development. The phenotype was particularly emphasized in plants grown in low soil nitrogen. The reduced ability of the extreme transgenic line Sg3 to recycle internal nitrogen from senescing lower leaves accounted for significant chlorosis in emerging younger leaves when plants were grown in low nutrient conditions. This study demonstrates that the agronomically important delayed-senescence ('stay-green') trait can be engineered into a monocot crop, and is the first example outside Arabidopsis of senescence modification using a homologous senescence-enhanced promoter.


Pure rotational coherent anti-Stokes Raman spectroscopy in mixtures of CO and N2.
We present a model for quantitative measurements in binary mixtures of nitrogen and carbon monoxide by the use of dual-broadband rotational coherent anti-Stokes Raman spectroscopy. The model has been compared with experimental rotational coherent anti-Stokes Raman scattering spectra recorded within the temperature range of 294-702 K. Temperatures and concentrations were evaluated by spectral fits using libraries of theoretically calculated spectra. The relative error of the temperature measurements was 1-2%, and the absolute error of the CO concentration measurements was <0.5% for temperatures < or =600 K. For higher temperatures, the gas composition was not chemically stable, and we observed a conversion of CO to CO2. The influence of important spectroscopic parameters such as the anisotropic polarizability and Raman line-broadening coefficients are discussed in terms of concentration measurements. In particular, it is shown that the CO concentration measurement was more accurate if N2-CO and CO-N2 line-broadening coefficients were included in the calculation. The applicability of the model for quantitative flame measurements is demonstrated by measuring CO concentrations in ethylene/air flames.


Neuroethical issues in pharmacological cognitive enhancement.
Neuroethics is an emerging field that in general deals with the ethics of neuroscience and the neuroscience of ethics. In particular, it is concerned with the ethical issues in the translation of neuroscience to clinical practice and in the public domain. Numerous ethical issues arise when healthy individuals use pharmacological substances known as pharmacological cognitive enhancers (PCEs) for non-medical purposes in order to boost higher-order cognitive processes such as memory, attention, and executive functions. However, information regarding their actual use, benefits, and harms to healthy individuals is currently lacking. Neuroethical issues that arise from their use include the unknown side effects that are associated with these drugs, concerns about the modification of authenticity and personhood, and as a result of inequality of access to these drugs, the lack of distributive justice and competitive fairness that they may cause in society. Healthy individuals might be coerced by social institutions that force them to take these drugs to function better. These drugs might enable or hinder healthy individuals to gain better moral and self-understanding and autonomy. However, how these drugs might achieve this still remains speculative and unknown. Hence, before concrete policy decisions are made, the cognitive effects of these drugs should be determined. The initiation of accurate surveys to determine the actual usage of these drugs by healthy individuals from different sections of the society is proposed. In addition, robust empirical research need to be conducted to delineate not only whether or not these drugs modify complex higher-order cognitive processes but also how they might alter important human virtues such as empathy, moral reasoning, creativity, and motivation in healthy individuals. WIREs Cogn Sci 2014, 5:533-549. doi: 10.1002/wcs.1306 For further resources related to this article, please visit the WIREs website. The author has declared no conflicts of interest for this article.


Vehicle detection using partial least squares.
Detecting vehicles in aerial images has a wide range of applications, from urban planning to visual surveillance. We describe a vehicle detector that improves upon previous approaches by incorporating a very large and rich set of image descriptors. A new feature set called Color Probability Maps is used to capture the color statistics of vehicles and their surroundings, along with the Histograms of Oriented Gradients feature and a simple yet powerful image descriptor that captures the structural characteristics of objects named Pairs of Pixels. The combination of these features leads to an extremely high-dimensional feature set (approximately 70,000 elements). Partial Least Squares is first used to project the data onto a much lower dimensional sub-space. Then, a powerful feature selection analysis is employed to improve the performance while vastly reducing the number of features that must be calculated. We compare our system to previous approaches on two challenging data sets and show superior performance.


Plasticity of DNA methylation in a nerve injury model of pain.
The response of the peripheral nervous system (PNS) to injury may go together with alterations in epigenetics, a conjecture that has not been subjected to a comprehensive, genome-wide test. Using reduced representation bisulfite sequencing, we report widespread remodeling of DNA methylation in the rat dorsal root ganglion (DRG) occurring within 24 h of peripheral nerve ligation, a neuropathy model of allodynia. Significant (P < 10(-4)) cytosine hyper- and hypo-methylation was found at thousands of CpG sites. Remodeling occurred outside of CpG islands. Changes affected genes with known roles in the PNS, yet methylome remodeling also involved genes that were not linked to neuroplasticity by prior evidence. Consistent with emerging models relying on genome-wide methylation and RNA-seq analysis of promoter regions and gene bodies, variation of methylation was not tightly linked with variation of gene expression. Furthermore, approximately 44% of the dynamically changed CpGs were located outside of genes. We compared their positions with the intergenic, tissue-specific differentially methylated CpGs (tDMCs) of an independent experimental set consisting of liver, spleen, L4 control DRG, and muscle. Dynamic changes affected those intergenic CpGs that were different between tissues (P < 10(-15)) and almost never the invariant portion of the methylome (those CpGs that were identical across all tissues). Our findings-obtained in mixed tissue-show that peripheral nerve injury leads to methylome remodeling in the DRG. Future studies may address which of the cell types found in the DRG, such as specific groups of neurons or non-neuronal cells are affected by which aspect of the observed methylome remodeling.


DNA methylation of multiple tumor-related genes in association with overexpression of DNA methyltransferase 1 (DNMT1) during multistage carcinogenesis of the pancreas.
To evaluate the significance of alterations in DNA methylation during multistage carcinogenesis of the pancreas, tissue samples of 13 peripheral pancreatic duct epithelia showing no remarkable histological changes without inflammatory background (DE), 20 peripheral pancreatic duct epithelia showing no remarkable histological changes with inflammatory background (DEI), 40 pancreatic intraepithelial neoplasias (PanIN) and 147 areas of ductal carcinoma were microdissected from surgically resected specimens from 58 patients and were embedded into agarose beads. The embedded tissue samples were subjected to methylation-specific PCR (MSP) to evaluate the DNA methylation status of the p14, p15, p16, p73, APC, hMLH1, MGMT, BRCA1, GSTP1, TIMP-3, CDH1 and DAPK-1 genes. The prevalence of DNA methylation of at least one of the 12 genes and the average number of methylated genes were significantly higher in both DEI (60% and 0.85 +/- 0.88, P = 0.0151 and P = 0.0224, respectively) and PanIN (67.5% and 0.95 +/- 0.85, P = 0.0014 and P = 0.0028, respectively) than in DE (15.4% and 0.15 +/- 0.38), and were further increased in ductal carcinoma (98.3% and 2.50 +/- 1.35, P < 0.0001 and P < 0.0001, respectively). The BRCA1, APC, p16 and TIMP-3 genes were frequently methylated in ductal carcinoma (60.3, 58.6, 39.3 and 30.9%, respectively). Considerable heterogeneity of DNA methylation status was observed among multiple microdissected areas from individual ductal carcinomas, and the number of methylated genes per area was significantly correlated with poorer tumor differentiation (P = 0.0249). The average number of methylated genes in ductal carcinomas was significantly correlated with DNMT1 protein expression level (P = 0.0093). These data suggest that accumulation of DNA methylation of multiple tumor-related genes is involved in multistage carcinogenesis of the pancreas from early precancerous stages to malignant progression and that DNMT1 protein overexpression may be responsible for this aberrant DNA methylation.


Topographic cues guide the attachment of diatom cells and algal zoospores.
Surface topography plays a key role in the colonization of substrata by the colonizing stages of marine fouling organisms. For the innovation of marine antifouling coatings, it is essential to understand how topographic cues affect the settlement of these organisms. In this study, tapered, spiked microstructures and discrete honeycombs of varying feature dimensions were designed and fabricated in order to examine the influence of topography on the attachment of zoospores of the green macroalga Ulva linza and cells of the diatom (microalga) Navicula incerta. Contrasting results were obtained with these two species of algae. Indeed, the preferred location of cells of N. incerta was dominated by attachment point theory, which suggested a positive correlation between the density of cells adhering and the amount of available attachment points, while the settlement of spores of U. linza was mainly regulated by both Wenzel roughness and local binding geometry.


IL-17A is functionally relevant and a potential therapeutic target in bullous pemphigoid.
IL-17A has been identified as key regulatory molecule in several autoimmune and chronic inflammatory diseases followed by the successful use of anti-IL-17 therapy, e.g. in ankylosing spondylitis and psoriasis. Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease with a high need for more specific, effective and safe treatment options. The aim of this study was to clarify the pathophysiological importance of IL-17A in BP. We found elevated numbers of IL-17A+ CD4+ lymphocytes in the peripheral blood of BP patients and identified CD3+ cells as major source of IL-17A in early BP skin lesions. IL17A and related genes were upregulated in BP skin and exome sequencing of 51 BP patients revealed mutations in twelve IL-17-related genes in 18 patients. We have subsequently found several lines of evidence suggesting a significant role of IL-17A in the BP pathogenesis: (i) IL-17A activated human neutrophils in vitro, (ii) inhibition of dermal-epidermal separation in cryosections of human skin incubated with anti-BP180 IgG and subsequently with anti-IL-17A IgG-treated leukocytes, (iii) close correlation of serum IL-17A levels and diseases activity in a mouse model of BP, (iv) IL17A-deficient mice were protected against autoantibody-induced BP, and (v) pharmacological inhibition of lL-17A reduced the induction of BP in mice. Our data give evidence for a pivotal role of IL-17A in the pathophysiology of BP and advocate IL-17A inhibition as potential novel treatment for this disease.


Characterization of a novel picornavirus isolated from moribund aquacultured clownfish.
Over the last decade, a number of USA aquaculture facilities have experienced periodic mortality events of unknown aetiology in their clownfish (Amphiprion ocellaris). Clinical signs of affected individuals included lethargy, altered body coloration, reduced body condition, tachypnea, and abnormal positioning in the water column. Samples from outbreaks were processed for routine parasitological, bacteriological, and virological diagnostic testing, but no consistent parasitic or bacterial infections were observed. Histopathological evaluation revealed individual cell necrosis and mononuclear cell inflammation in the branchial cavity, pharynx, oesophagus and/or stomach of four examined clownfish, and large basophilic inclusions within the pharyngeal mucosal epithelium of one fish. Homogenates from pooled external and internal tissues from these outbreaks were inoculated onto striped snakehead (SSN-1) cells for virus isolation and cytopathic effects were observed, resulting in monolayer lysis in the initial inoculation and upon repassage. Transmission electron microscopy of infected SSN-1 cells revealed small round particles (mean diameter=20.0-21.7 nm) within the cytoplasm, consistent with the ultrastructure of a picornavirus. Full-genome sequencing of the purified virus revealed a novel picornavirus most closely related to the bluegill picornavirus and other members of the genus Limnipivirus. Additionally, pairwise protein alignments between the clownfish picornavirus (CFPV) and other known members of the genus Limnipivirus yielded results in accordance with the current International Committee on Taxonomy of Viruses criteria for members of the same genus. Thus, CFPV represents a proposed new limnipivirus species. Future experimental challenge studies are needed to determine the role of CFPV in disease.


A prospective study of protein-specific assays used to investigate idiopathic thrombocytopenic purpura.
Idiopathic thrombocytopenic purpura (ITP) is a disorder in which platelets, sensitized by autoantibodies, are destroyed by the reticuloendothelial system. The diagnosis of ITP has been a clinical one because assays measuring platelet-associated IgG (PAIgG) have low specificity. The recently introduced assays that measure antibodies against specific platelet glycoproteins (GP) offer the possibility of improved specificity. In this report we describe two prospective studies. In the first study we compared two protein-specific assays (AC and MAIPA) looking for the presence of autoantibodies against GP IIb/IIIa in 81 patient samples. These results were compared with an immunoradiometric assay for PAIgG. The second study investigated the enhanced sensitivity of measuring anti-GP Ib/IX autoantibodies in 76 patient samples. The protein-specific assays were able to differentiate immune from non-immune thrombocytopenia (specificity 91%, sensitivity 39%), whereas the PAIgG assay could not (specificity 19%, sensitivity 78%). The addition of the Ib/IX AC assay maintained a specificity of 92% while increasing the diagnostic sensitivity to 66%. In contrast to the PAIgG assay, there was no correlation between the platelet count and the likelihood or degree of positivity within the control samples using the glycoprotein assays. These studies confirm that glycoprotein assays can be used as diagnostic tests for ITP.


Self-reported occupational exposure to chemical and physical factors and risk of skin problems: a 3-year follow-up study of the general working population of Norway.
Prospective studies on occupational dermatoses in the general working population are sparse. This study investigated prospectively the impact of self-reported occupational exposure to chemicals and physical factors on the risk of skin problems. The cohort comprised respondents drawn randomly from the general population in Norway, who were registered employed in 2006 and 2009 (n = 6,745). Indoor dry air (odds ratio (OR) 1.3; 95% confidence interval (95% CI) 1.1-1.6) was a significant baseline predictor of skin problems at follow-up, whereas exposure to cleaning products (OR 1.7; 95% CI 1.2-2.5), water (OR 1.4; 95% CI 1.1-1.9) and indoor dry air (OR 1.6; 95% CI 1.1-2.1) at both measurement time-points was significantly associated with skin problems. The population risk attributable to these factors was 16%. This study quantified the contribution of occupational exposure factors to skin problems in the general working population of Norway.


Connecting the obesity and the narcissism epidemics.
Obesity and metabolic syndromes are major threats to health in both developed and developing countries. This opinion article is a holistic attempt to understand the obesity epidemic, by connecting it to the widespread narcissism in society. The narcissism epidemic refers to an increased prevalence of status-striving individualism and a decreased sense of community, observed in Westerns populations and spreading worldwide. Based on social personality and evolutionary psychology approaches, I speculate that this rise of narcissism underlies a steep social hierarchy resulting in increase of social stress. This social stress markedly affects individuals who are sensitive to social hierarchy dominance due to their personality, yet are relegated at a lower social position. I speculate that over-eating is one major mechanism for coping with this stress, and discuss the possibility that visceral fat may constitute an adaptive behaviour to the lower social hierarchy position, which is perceived as unjust. Connecting the prevalence of obesity to the narcissism epidemic allows for a more thorough examination of factors, which contribute to obesity, which includes early difficult childhood experience, lower rank, and the overall competitive framework of the society.


Clinical Presentation of Mucopolysaccharidosis Type II (Hunter's Syndrome).
We present a rare case of mucopolysaccharidosis (MPS) with a typical presentation of mental retardation and absence of corneal clouding. The purpose of presenting this case report is to highlight the distinctive manifestation of MPS (Hunter's disease) and to provide a concise report of Hunter's disease for medical practitioners with the hope that such information will help identify boys earlier in the course of their disease. This report is of a 7-year-old boy who presented to the children outpatient through a referral with a history of inability to grasp objects, inability to express self, and coarse skin, which started 5 years ago. On examination, he was short statured, with a big head, protruding abdomen, coarse skin, swollen wrist joints, and clubbed fingers. There was mild mental retardation. Investigations revealed mucopolysaccharides in urine ad radiographic findings were in keeping with diagnosis. Based on the clinical features and radiological findings, one can diagnose a case of MPS. However, careful and critical approach is necessary to exactly diagnose the type of MPS as enzymatic studies are not available in most centers.


Specific DNA replication mutations affect telomere length in Saccharomyces cerevisiae.
To investigate the relationship between the DNA replication apparatus and the control of telomere length, we examined the effects of several DNA replication mutations on telomere length in Saccharomyces cerevisiae. We report that a mutation in the structural gene for the large subunit of DNA replication factor C (cdc44/rfc1) causes striking increases in telomere length. A similar effect is seen with mutations in only one other DNA replication gene: the structural gene for DNA polymerase alpha (cdc17/pol1) (M.J. Carson and L. Hartwell, Cell 42:249-257, 1985). For both genes, the telomere elongation phenotype is allele specific and appears to correlate with the penetrance of the mutations. Furthermore, fluorescence-activated cell sorter analysis reveals that those alleles that cause elongation also exhibit a slowing of DNA replication. To determine whether elongation is mediated by telomerase or by slippage of the DNA polymerase, we created cdc17-1 mutants carrying deletions of the gene encoding the RNA component of telomerase (TLC1). cdc17-1 strains that would normally undergo telomere elongation failed to do so in the absence of telomerase activity. This result implies that telomere elongation in cdc17-1 mutants is mediated by the action of telomerase. Since DNA replication involves transfer of the nascent strand from polymerase alpha to replication factor C (T. Tsurimoto and B. Stillman, J. Biol. Chem. 266:1950-1960, 1991; T. Tsurimoto and B. Stillman, J. Biol. Chem. 266:1961-1968, 1991; S. Waga and B. Stillman, Nature [London] 369:207-212, 1994), one possibility is that this step affects the regulation of telomere length.


Epigenetic and antioxidant effects of dietary isothiocyanates and selenium: potential implications for cancer chemoprevention.
There is evidence from epidemiological studies suggesting that increased consumption of cruciferous vegetables may protect against specific cancers more effectively than total fruit and vegetable intake. These beneficial effects are attributed to the glucosinolate breakdown products, isothiocyanates (ITC). Similarly, selenium (Se) consumption has also been inversely associated with cancer risk and as an integral part of many selenoproteins may influence multiple pathways in the development of cancer. This paper will briefly review the current state of knowledge concerning the effect of Se and ITC in cancer development with a particular emphasis on its antioxidant properties, and will also address whether alterations in DNA methylation may be a potential mechanism whereby these dietary constituents protect against the carcinogenic process. Furthermore, we will discuss the advantages of combining ITC and Se to benefit from their complementary mechanisms of action to potentially protect against the alterations leading to neoplasia. Based on this review it may be concluded that an understanding of the impact of ITC and Se on aberrant DNA methylation in relation to factors modulating gene-specific and global methylation patterns, in addition to the effect of these food constituents as modulators of key selenoenzymes, such as gastrointestinal glutathione peroxidase-2 (GPx2) and thioredoxin reductase-1 (TrxR1), may provide insights into the potential synergy among various components of a plant-based diet that may counteract the genetic and epigenetic alterations that initiate and sustain neoplasia.


Neonatal Skin-to-Skin Contact: Implications for Learning and Autonomic Nervous System Function in Infants With Congenital Heart Disease.
Infants with complex congenital heart disease (CCHD) often develop neurodevelopmental disabilities. Cognitive abilities are associated with vagally mediated autonomic function. Skin-to-skin contact (SSC) interventions enhance infant neurodevelopment and autonomic function in other high-risk populations. To examine the effects of a neonatal SSC intervention on learning and autonomic function in 3-month-old infants: infants with CCHD who received neonatal SSC ( n = 10), typically developing (TD) infants ( n = 16), and infants with CCHD without SSC ( n = 10). This secondary data analysis measured cognitive function using the mobile paradigm (MP), a classic measure of learning based on operant conditioning. Autonomic function was assessed with heart rate (HR) and HR variability (HRV). Data were analyzed with repeated-measures general linear mixed modeling with α = .10 for this exploratory study. Learning rates were TD = 75%, cardiac-SSC = 70%, and cardiac-control = 40%. Learners demonstrated significant reductions in HRV during the MP; nonlearners exhibited no change. TD and cardiac-SSC groups exhibited increases in HR and reductions in HRV during the MP. No significant changes occurred in the cardiac-control group. Nonlinear HRV during the MP differed only in the TD group. Findings suggest improvements in cognitive and autonomic development in 3-month-old infants with CCHD who received neonatal SSC. Learning and autonomic function results in infants with CCHD who had not received SSC suggest reduced capacity to muster the physiologic resources to carry out this cognitive task. Findings provide preliminary evidence in support of implementation of SSC with infants with CCHD and support additional research.


Status of open access in the biomedical field in 2005.
This study was designed to document the state of open access (OA) in the biomedical field in 2005. PubMed was used to collect bibliographic data on target articles published in 2005. PubMed, Google Scholar, Google, and OAIster were then used to establish the availability of free full text online for these publications. Articles were analyzed by type of OA, country, type of article, impact factor, publisher, and publishing model to provide insight into the current state of OA. Twenty-seven percent of all the articles were accessible as OA articles. More than 70% of the OA articles were provided through journal websites. Mid-rank commercial publishers often provided OA articles in OA journals, while society publishers tended to provide OA articles in the context of a traditional subscription model. The rate of OA articles available from the websites of individual authors or in institutional repositories was quite low. In 2005, OA in the biomedical field was achieved under an umbrella of existing scholarly communication systems. Typically, OA articles were published as part of subscription journals published by scholarly societies. OA journals published by BioMed Central contributed to a small portion of all OA articles.


Symptom-based presentation of chronic rhinosinusitis and symptom-specific outcomes after endoscopic sinus surgery.
Very few studies have comprehensively examined specific symptom outcomes of endoscopic sinus surgery (ESS). The purpose of this study was to define the individual symptoms of a cohort of patients with medically refractory chronic rhinosinusitis (CRS) using visual analog scale (VAS) scores as well as report symptom-based outcomes after ESS. Patients with medically refractory CRS presenting for surgical management were asked to evaluate baseline symptoms using 10-cm VAS measures. Participants were asked to rank their most debilitating symptoms in descending order. VAS scores were assessed postoperatively at 3, 6, 12, and 18 months. The Kruskal-Wallis test was used to assess improvement in mean symptom VAS scores at each of the postoperative time points. Nasal congestion elicited the highest preoperative VAS score with an average of 6.5, followed by fatigue (6.0), headache (5.8), decreased sense of smell (5.5), nasal drainage (5.5), and facial pain-pressure (5.5). Headache was the most commonly reported disabling condition. Follow-up data after ESS was available for 207 patients. Average VAS scores for 6 of 7 symptoms showed significant and sustainable postoperative improvement at 3, 6, 12, and 18 months after surgery (p < 0.001). Improvement in VAS score for headache was not statistically significant (p > 0.700). This study indicates that patients with medically refractory CRS presenting for surgery complain of associated symptoms with great frequency. ESS results in both statistically and clinically significant improvements in six of seven symptoms. Headache, which was the most highly ranked disabling symptom, did not show significant improvement from baseline.


Nicotinamide riboside alleviates alcohol-induced depression-like behaviours in C57BL/6J mice by altering the intestinal microbiota associated with microglial activation and BDNF expression.
The gut microbiota play an important role in many central nervous system diseases through the gut microbiota-brain axis. Recent studies suggest that nicotinamide riboside (NR) has neuroprotective properties. However, it is unknown whether NR can prevent or protect against alcohol-induced depression. Furthermore, it is unclear whether its therapeutic action involves changes in the composition of the gut microbiome. Here, we investigated the effects of NR in the mouse model of alcohol-induced depression. Treatment with NR improved the alcohol-induced depressive behaviour in mice. In addition, NR decreased the number of activated microglia in the hippocampus, and it reduced the levels of pro-inflammatory (IL-1β, IL-6, and TNF-α) and anti-inflammatory (IL-10 and TGF-β) cytokines in the brain of mice with alcohol-induced depression. Furthermore, NR significantly upregulated BDNF and diminished the inhibition of the AKT/GSK3β/β-catenin signalling pathway in the hippocampus of these mice. 16S rRNA sequencing revealed that, compared with control and NR-treated mice, the gut microbiome richness and composition were significantly altered in the depressed mice. Spearman's correlation analysis showed that differential gut bacterial genera correlated with the levels of inflammation-related cytokines and BDNF in the brain. After faecal microbiota transplantation, cognitive behaviours, microglial activity, levels of cytokines and BDNF, and activation state of the AKT/GSK3β/β-catenin signalling pathway (which is downstream of the BDNF receptor, TrkB) in recipient mice were similar to those in donor mice. Collectively, our findings show that NR dietary supplementation protects against alcohol-induced depression-like behaviours, possibly by altering the composition of the gut microbiota.


Dynamic changes in the mental rotation network revealed by pattern recognition analysis of fMRI data.
We investigated the temporal dynamics and changes in connectivity in the mental rotation network through the application of spatio-temporal support vector machines (SVMs). The spatio-temporal SVM [Mourao-Miranda, J., Friston, K. J., et al. (2007). Dynamic discrimination analysis: A spatial-temporal SVM. Neuroimage, 36, 88-99] is a pattern recognition approach that is suitable for investigating dynamic changes in the brain network during a complex mental task. It does not require a model describing each component of the task and the precise shape of the BOLD impulse response. By defining a time window including a cognitive event, one can use spatio-temporal fMRI observations from two cognitive states to train the SVM. During the training, the SVM finds the discriminating pattern between the two states and produces a discriminating weight vector encompassing both voxels and time (i.e., spatio-temporal maps). We showed that by applying spatio-temporal SVM to an event-related mental rotation experiment, it is possible to discriminate between different degrees of angular disparity (0 degrees vs. 20 degrees , 0 degrees vs. 60 degrees , and 0 degrees vs. 100 degrees ), and the discrimination accuracy is correlated with the difference in angular disparity between the conditions. For the comparison with highest accuracy (0 degrees vs. 100 degrees ), we evaluated how the most discriminating areas (visual regions, parietal regions, supplementary, and premotor areas) change their behavior over time. The frontal premotor regions became highly discriminating earlier than the superior parietal cortex. There seems to be a parcellation of the parietal regions with an earlier discrimination of the inferior parietal lobe in the mental rotation in relation to the superior parietal. The SVM also identified a network of regions that had a decrease in BOLD responses during the 100 degrees condition in relation to the 0 degrees condition (posterior cingulate, frontal, and superior temporal gyrus). This network was also highly discriminating between the two conditions. In addition, we investigated changes in functional connectivity between the most discriminating areas identified by the spatio-temporal SVM. We observed an increase in functional connectivity between almost all areas activated during the 100 degrees condition (bilateral inferior and superior parietal lobe, bilateral premotor area, and SMA) but not between the areas that showed a decrease in BOLD response during the 100 degrees condition.


Maturational changes in endothelium-derived relaxations in newborn piglet pulmonary circulation.
It is accepted knowledge that the endothelium can profoundly affect vascular tone through the release of vasoactive substances. The maturational changes in the role of the endothelium-derived relaxing factor (EDRF) and ATP-dependent K+ channels in the neonatal pulmonary circulation were investigated in isolated perfused lungs from 1- and 7-day-old piglets. The EDRF inhibitor, N omega-nitro-L-arginine (L-NNA), had potent dose-dependent constrictor effects on the pulmonary vasculature with normal and raised tone. The constrictor effect of L-NNA was greater (P < 0.05) in the 1-day-old than in the 7-day-old lungs and was significantly (P < 0.005) attenuated by pretreatment with the EDRF precursor, L-arginine. Furthermore, we studied the possibility of developmental changes in the sensitivity of smooth muscle cells to EDRF by testing sodium nitroprusside, nitric oxide, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP). All caused a decrease in perfusion pressure, but only sodium nitroprusside elicited a greater (P < 0.01) effect in the 1-day-old. Endothelin-1 (ET-1) and bradykinin (BK) elicited dilator responses that were significantly (P < 0.05) reduced in the presence of L-NNA. Interestingly, the dilator response to ET-1 was more marked (P < 0.001) in the younger group, whereas no age difference was noted with BK. Finally, lemakalim, a K+ channel activator, caused a vasodilation of equal magnitude at both ages. In summary, EDRF and ATP-dependent K+ channels appear to play a role in the control of the newborn piglet pulmonary vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)


Canonical and Cross-reactive Binding of NK Cell Inhibitory Receptors to HLA-C Allotypes Is Dictated by Peptides Bound to HLA-C.
Human natural killer (NK) cell activity is regulated by a family of killer cell immunoglobulin-like receptors (KIRs) that bind human leukocyte antigen (HLA) class I. Combinations of KIR and HLA genotypes are associated with disease, including susceptibility to viral infection and disorders of pregnancy. KIR2DL1 binds HLA-C alleles of group C2 (Lys80). KIR2DL2 and KIR2DL3 bind HLA-C alleles of group C1 (Asn80). However, this model cannot explain HLA-C allelic effects in disease or the impact of HLA-bound peptides. The goal of this study was to determine the extent to which the endogenous HLA-C peptide repertoire can influence the specific binding of inhibitory KIR to HLA-C allotypes. The impact of HLA-C bound peptide on inhibitory KIR binding was investigated taking advantage of the fact that HLA-C*05:01 (HLA-C group 2, C2) and HLA-C*08:02 (HLA-C group 1, C1) have identical sequences apart from the key KIR specificity determining epitope at residues 77 and 80. Endogenous peptides were eluted from HLA-C*05:01 and used to test the peptide dependence of KIR2DL1 and KIR2DL2/3 binding to HLA-C*05:01 and HLA-C*08:02 and subsequent impact on NK cell function. Specific binding of KIR2DL1 to the C2 allotype occurred with the majority of peptides tested. In contrast, KIR2DL2/3 binding to the C1 allotype occurred with only a subset of peptides. Cross-reactive binding of KIR2DL2/3 with the C2 allotype was restricted to even fewer peptides. Unexpectedly, two peptides promoted binding of the C2 allotype-specific KIR2DL1 to the C1 allotype. We showed that presentation of endogenous peptides or HIV Gag peptides by HLA-C can promote KIR cross-reactive binding. KIR2DL2/3 binding to C1 is more peptide selective than that of KIR2DL1 binding to C2, providing an explanation for KIR2DL3-C1 interactions appearing weaker than KIR2DL1-C2. In addition, cross-reactive binding of KIR is characterized by even higher peptide selectivity. We demonstrate a hierarchy of functional peptide selectivity of KIR-HLA-C interactions with relevance to NK cell biology and human disease associations. This selective peptide sequence-driven binding of KIR provides a potential mechanism for pathogen as well as self-peptide to modulate NK cell activation through altering levels of inhibition.


Authenticating production origin of gilthead sea bream (Sparus aurata) by chemical and isotopic fingerprinting.
Recent EU legislation (EC/2065/2001) requires that fish products, of wild and farmed origin, must provide consumer information that describes geographical origin and production method. The aim of the present study was to establish methods that could reliably differentiate between wild and farmed European gilthead sea bream (Sparus aurata). The methods that were chosen were based on chemical and stable isotopic analysis of the readily accessible lipid fraction. This study examined fatty acid profiles by capillary gas chromatography and the isotopic composition of fish oil (delta(13)C, delta(18)O), phospholipid choline nitrogen (delta(15)N) and compound specific analysis of fatty acids (delta(13)C) by isotope ratio mass spectroscopy as parameters that could reliably discriminate samples of wild and farmed sea bream. The sample set comprised of 15 farmed and 15 wild gilthead sea bream (Sparus aurata), obtained from Greece and Spain, respectively. Discrimination was achieved using fatty acid compositions, with linoleic acid (18:2n-6), arachidonic acid (20:4n-6), stearic acid (18:0), vaccenic acid (18:1n-7) and docosapentaenoic acid (22:5n-3) providing the highest contributions for discrimination. Principle components analysis of the data set highlighted good discrimination between wild and farmed fish. Factor 1 and 2 accounted for >70% of the variation in the data. The variables contributing to this discrimination were: the fatty acids 14:0, 16:0, 18:0, 18:1n-9, 18:1n-7, 22:1n-11, 18:2n-6 and 22:5n-3; delta(13)C of the fatty acids 16:0, 18:0, 16:1n-7, 18:1n-9, 20:5n-3 and 22:6n-3; Bulk oil fraction delta(13)C; glycerol/choline fraction bulk delta(13)C; delta(15)N; % N; % lipid.


The mitogaligin protein is addressed to the nucleus via a non-classical localization signal.
Mitogaligin, a protein encoded by galig, an internal cytotoxic gene of the galectin-3 locus, is mostly a mitochondrial protein. Mitochondrial targeting is due to an already identified mitochondrial localization signal. Interaction of mitogaligin with mitochondria leads to cytochrome c cytosolic leakage and ultimately to cell death. We have previously pointed out that mitogaligin can also be directed to the nucleus when the mitochondrial addressing signal is inactivated, indicating a possible dual intracellular localization of the protein. When expressed in the nucleus, mitogaligin exhibits also apoptotic properties leading to cell death. In this report, we show that nuclear addressing of mitogaligin depends on a sequence differing from classical signals containing basic, lysine or proline-tyrosine rich residues. The signal consists of a long sequence of amino acids residues based on a series of a short repetitive degenerated sequence.


What do external consultants from private and not-for-profit companies offer healthcare commissioners? A qualitative study of knowledge exchange.
The use of external consultants from private and not-for-profit providers in the National Health Service (NHS) is intended to improve the quality of commissioning. The aim of this study was to learn about the support offered to healthcare commissioners, how external consultants and their clients work together and the perceived impact on the quality of commissioning. NHS commissioning organisations and private and not-for-profit providers. Mixed methods case study of eight cases. 92 interviews with external consultants (n=36), their clients (n=47) and others (n=9). Observation of 25 training events and meetings. Documentation, for example, meeting minutes and reports. Constant comparison. Data were coded, summarised and analysed by the research team with a coding framework to facilitate cross-case comparison. In the four contracts presented here, external providers offered technical solutions (eg, software tools), outsourcing and expertise including project management, data interpretation and brokering relationships with experts. In assessing perceived impact on quality of commissioning, two contracts had limited value, one had short-term benefits and one provided short and longer term benefits. Contracts with commissioners actively learning, embedding and applying new skills were more valued. Other elements of success were: (1) addressing clearly agreed problems of relevance to managerial and operational staff (2) solutions co-produced at all organisational levels (3) external consultants working directly with clients to interpret data outputs to inform locally contextualised commissioning strategies. Without explicit knowledge exchange strategies, outsourcing commissioning to external providers resulted in the NHS clients becoming dependent. NHS commissioning will be disadvantaged if commissioners both fail to learn in the short term from the knowledge of external providers and in the longer term lose local skills. Knowledge exchange mechanisms are a vital component of commissioning and should be embedded in external provider contracts.


Fast dynamics of a hydrogen-bonding glass forming liquid: Chemical exchange-induced spectral diffusion in 2D IR spectroscopy.
Polarization-selective Two Dimensional Infrared (2D IR) and IR pump-probe spectroscopies have been performed on the hydrogen bonding glass forming liquid 2-biphenylmethanol doped with the long-lived vibrational probe phenylselenocyanate over a wide range of temperatures. The spectral diffusion seen in the 2D spectra was found to have a large polarization dependence, in large excess of what is predicted by standard theory. This anomaly was explained by decomposing the 2D spectra into hydrogen-bonding and non-bonding components, which exchange through large-angle orientational motion. By adapting chemical exchange theories, parameters for the component peaks were then calculated by fitting the polarization-dependent spectral diffusion and the pump-probe anisotropy. A model of highly heterogeneous exchange and orientational dynamics was used to explain the observed time dependences as a function of temperature on fast time scales. The experimental observations, the kinetic modeling, and physical arguments lead to the determination of the times for interconversion of slow dynamics structural domains to fast dynamics structural domains in the supercooled liquid as a function of temperature. The slow to fast domain interconversion times range from 40 ps at 355 K to 5000 ps at 270 K.


Antifungal properties of silver nanoparticles against indoor mould growth.
The presence of moulds in indoor environments causes serious diseases and acute or chronic toxicological syndromes. In order to inhibit or prevent the growth of microorganisms on building materials, the disruption of their vital processes or the reduction of reproduction is required. The development of novel techniques that impair the growth of microorganisms on building materials is usually based on silver nanoparticles (AgNPs). It makes them an alternative to other biocides. AgNPs have proven antibacterial activity and became promising in relation to fungi. The aim of the study was to assess growth and morphology of mycelia of typical indoor fungal species: Penicillium brevicompactum, Aspergillus fumigatus, Cladosporium cladosporoides, Chaetomium globosum and Stachybotrys chartarum as well as Mortierella alpina, cultured on agar media. The antifungal activity of AgNPs was also tested in relation to C. globosum and S. chartarum grown on the surface of gypsum drywall. It was found that the presence of AgNPs in concentrations of 30-200mg/l significantly decreased the growth of fungi. However, in the case of M. alpina, AgNPs stimulated its growth. Moreover, strong changes in moulds morphology and colour were observed after administration of AgNPs. Parameters of conidiophores/sporangiophores varied depending on mould region and changed significantly after treatment with AgNPs. The experiments have shown antifungal properties of AgNPs against common indoor mould species. Their application to building materials could effectively protect indoor environments from mould development. However, consideration must be given to the fact that the growth of some fungal strains might be stimulated by AgNPs.


Glycine decarboxylase is a transcriptional target of MYCN required for neuroblastoma cell proliferation and tumorigenicity.
Genomic amplification of the oncogene MYCN is a major driver in the development of high-risk neuroblastoma, a pediatric cancer with poor prognosis. Given the challenge in targeting MYCN directly for therapy, we sought to identify MYCN-dependent metabolic vulnerabilities that can be targeted therapeutically. Here, we report that the gene encoding glycine decarboxylase (GLDC), which catalyzes the first and rate-limiting step in glycine breakdown with the production of the one-carbon unit 5,10-methylene-tetrahydrofolate, is a direct transcriptional target of MYCN. As a result, GLDC expression is markedly elevated in MYCN-amplified neuroblastoma tumors and cell lines. This transcriptional upregulation of GLDC expression is of functional significance, as GLDC depletion by RNA interference inhibits the proliferation and tumorigenicity of MYCN-amplified neuroblastoma cell lines by inducing G1 arrest. Metabolomic profiling reveals that GLDC knockdown disrupts purine and central carbon metabolism and reduces citrate production, leading to a decrease in the steady-state levels of cholesterol and fatty acids. Moreover, blocking purine or cholesterol synthesis recapitulates the growth-inhibitory effect of GLDC knockdown. These findings reveal a critical role of GLDC in sustaining the proliferation of neuroblastoma cells with high-level GLDC expression and suggest that MYCN amplification is a biomarker for GLDC-based therapeutic strategies against high-risk neuroblastoma.


Recurrent amelanotic melanoma of nasal cavity: Biological variability and unpredictable behavior of mucosal melanoma. A case report.
The aim of this report is to present a case of a patient with a recurrent nasal cavity amelanotic melanoma (AM), with emphasis on diagnosis and therapy options of this clinical entity. A 65-year-old female patient presented with pain in the right cheek region and nasal obstruction. In 2013, she was diagnosed with mucosal melanoma (MM) of the left nasal cavity. After endoscopic surgery and radiotherapy, the patient was followed by the oncology team. Five years after the initial diagnosis, rhinoscopy showed a tumorous formation in the right nasal cavity. The tumor mass was without black discoloration and was the same color as the surrounding nasal mucosa. Microscopic examination after biopsy of the tumor confirmed amelanotic MM. The patient underwent an additional endoscopic surgery. A complete standard diagnostic workup for MM found metastases in head and neck lymph nodes, on both sides. MMs of head and neck are uncommon malignancies. Unique biology of MM cells causes a high rate of recurrences. This report presents an example of recurrent AM of the nasal cavity, in treatment with checkpoint inhibitor (pembrolizumab), which could provide a good therapy option for patients with MM.


Response of multiple recurrent TaT1 bladder cancer to intravesical apaziquone (EO9): comparative analysis of tumor recurrence rates.
Previous studies have demonstrated that intravesical administration of apaziquone (EOquin) has ablative activity against superficial bladder cancer marker lesions with 8 out of 12 complete responses recorded. We present a comparison between the rates of tumor recurrence before and after treatment with apaziquone. The rate of tumor recurrence after treatment with apaziquone was compared with each patient's historical record of recurrences obtained from a retrospective analysis of the patients' case notes. The time to each recurrence event before apaziquone treatment and the time to the first recurrence after apaziquone treatment were recorded, and the data were analyzed using a population-averaged linear regression model using Stata Release, version 9.2, software. Of the eight complete responses obtained in the Phase I study, tumor recurrence occurred in 4 patients and the remaining 4 patients remained disease free after a median follow-up of 31 months. The time to the first recurrence after apaziquone treatment was significantly longer (P <0.001) compared with the historical pattern and recurrence interval before apaziquone. Before apaziquone instillation, the mean +/- SE recurrence rate and tumor rate per year was 1.5 +/- 0.2 and 4.8 +/- 1.2, respectively, and these decreased to 0.6 +/- 0.25 and 1.5 +/- 0.8, respectively, after apaziquone treatment (P <0.05). The results of this study indicate that early recurrences after treatment with apaziquone are infrequent and the interval to recurrence is significantly greater compared with the historical recurrence times for these patients. Larger prospective randomised trials are warranted to confirm these results.


Full scale membrane bioreactor treatment of hospital wastewater as forerunner for hot-spot wastewater treatment solutions in high density urban areas.
Membrane Bioreactors (MBR) are a very attractive option for the treatment of hospital wastewater and elimination of pharmaceuticals in high density urban areas. The present investigation showed that, depending on the substance, between 19% and 94% of the level of antibiotics found in the environment originate from hospitals. Because of their ecotoxic potential, hospital wastewaters can have a significant impact on the environment. The segregation of these wastewaters and their separate treatment at the source can reduce the entry of drugs in waterways and enable water reuse after adequate polishing treatment processes.


Effectively designed molecularly imprinted polymers for selective isolation of the antidiabetic drug metformin and its transformation product guanylurea from aqueous media.
In the present study, two novel molecularly imprinted polymers (MIPs) with remarkable recognition properties for metformin and its transformation product, guanylurea, have been prepared for their selective, enrichment, isolation and removal from aqueous media. The prepared adsorbents were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and swelling experiments. The performance of the prepared MIPs was evaluated by various parameters including the influence of pH, contact time, temperature and initial compound concentration. The effects on the adsorption behavior of the removal process parameters were studied and the equilibrium data were fitted by the Langmuir and Freundlich models. Due to the imprinting effect, adsorption performance of MIPs was always superior to its corresponding NIP (non-imprinted polymer), with maximum adsorption capacity ∼80 mg g(-1) for both MIPs. Stability and reusability of the MIPs up to the 5th cycle meant that they could be applied repeatedly without losing substantial removal ability. In the next step, the prepared MIP nanoparticles were evaluated as sorbents in a dispersive solid phase extraction (D-SPE) configuration for selective enrichment and determination of metformin and guanylurea in different aqueous matrices. Under the working extraction conditions, the D-SPE method showed good linearity in the range of 50-1000 ng L(-1), repeatability of the extractions (RSD 2.1-5.1%, n=3), and low limits of detection (1.5-3.4 ng L(-1)). The expanded uncertainty of the data obtained was estimated following a bottom-up approach. The proposed method combined the advantages of MIPs and D-SPE, and it could become an alternative tool for analyzing the residues of METF and its transformation product GUA in complex water matrices, such as wastewaters.


Transfer of Epstein-Barr virus receptors to receptor-negative cells permits virus penetration and antigen expression.
Epstein-Barr virus (EBV) receptors were implanted into the membranes of receptor-negative cells, using Sendai virus envelopes as vehicles. The presence of the receptors in the target cell membrane was demonstrated by monitoring the fate of radioiodinated donor membranes. Receptors could be detected for at least 36 hr after implantation. [3H]Thymidine-labeled EBV bound efficiently to receptor-implanted cells but not to control cells. Binding was inhibited by an excess of nonlabeled virus. Of the [3H]thymidine-labeled EBV DNA, 50-75% was found inside the receptor-implanted, EBV-exposed cells 24 hr after the infection. The viral genome was functionally active in B lymphocyte-derived cell lines of human, murine, and baboon origin; in T lymphocyte-derived lines of human and murine origin; in mouse fibroblasts; and in freshly explanted mouse lymphocytes, as shown by the expression of EBV-determined nuclear, early, and viral capsid antigens.


Progressive hearing loss after transverse temporal bone fracture.
Transverse fractures often violate the otic capsule and commonly, although not invariably, result in immediate and profound sensorineural hearing loss. The pathogenic mechanisms producing sensorineural hearing loss include direct trauma to the cochlear nerve, disruption of the membranous labyrinth, vascular compromise or hemorrhage into the inner ear, perilymphatic fistula, and endolymphatic hydrops. The last two mechanisms account for the occasional patient who develops progressive sensorineural hearing loss after the initial insult. On early posttraumatic evaluation three patients were discovered to have transverse fractures and residual auditory function. Deterioration of hearing led to middle-ear exploration with closure of perilymphatic fistulas. Hearing was preserved in two patients. Diagnosis of posttraumatic perilymphatic fistulas requires early audiometric assessment, high-resolution computed tomographic scanning of the temporal bones to detect fracture of the otic capsule and pneumolabyrinth, and a high index of clinical suspicion.


Cross-Sector Collaborations And Partnerships: Essential Ingredients To Help Shape Health And Well-Being.
Cross-sector collaborations and partnerships are an essential component of the strategy to improve health and well-being in the United States. While their importance is unquestioned, their impact on population health has not yet been fully observed. Cross-sector collaboration also is the second Action Area of the Robert Wood Johnson Foundation's four-part Action Framework to build a Culture of Health in the United States. This Action Area has three constituent parts or drivers: the number, breadth, and quality of successful cross-sector partnerships; the adequacy of investment in these partnerships; and the adoption of policies needed to support them. In this article we analyze outstanding examples of partnership-driven work. We also study the challenges of how partner sectors outside the formal health system, such as organizations working in the education or housing sectors, can effectively lead collaborations. We identify models of leadership that maximize the potential of all participants. We also propose the adoption of models better suited to supporting effective cross-sector collaborations. The analysis builds the evidence base for understanding and sustaining the impact of cross-sector collaboration on population health.


Quantification and clinical relevance of gene amplification at chromosome 17q12-q21 in human epidermal growth factor receptor 2-amplified breast cancers.
Human epidermal growth factor receptor 2 (HER2)-amplified breast cancers represent a tumor subtype with chromosome 17q rearrangements that lead to frequent gene amplifications. The aim of this study was to quantify the amplification of genes located on chromosome 17q and to analyze the relations between the pattern of gene amplifications and the patients' characteristics and survival. Patients with HER2-positive breast tumors (HER2 score of 3+ by immunohistochemistry or positive for HER2 amplification by fluorescence in situ hybridization (FISH)) (n = 86) and with HER2-negative breast tumors (n = 40) (negative controls) were included in this study. Using a quantitative polymerase chain reaction method and DNA extracted from frozen tumor specimens, 11 genes (MED1, STARD3, HER2, GRB7, THRA, RARA, TOP2A, IGFBP4, CCR7, KRT20, KRT19 and GAS), which are localized within Chr17q12-q21 and have a putative role in breast cancer development, were quantified. Relapse-free and overall survival rates were estimated from the date of surgery to the date of the event of interest (recurrence or death) using the Kaplan-Meier method. Gene amplification was observed only in HER2-positive tumors, and the frequency of amplification decreased with the distance of the gene from HER2. HER2 presented the highest level of amplification. TOP2A was not included in the smallest region of amplification involving HER2. Amplification of RARA, KRT20 and KRT19 was significantly associated with node-positive breast cancer (P = 0.030, P = 0.002 and P = 0.033, respectively). During a median follow-up period of 55 months (range, 6 to 81 months), the subgroup of patients with hormone receptor-negative cancer and without TOP2A amplification showed the worst survival (relapse-free survival: hazard ratio (HR) = 0.29, 95% confidence interval (95% CI), 0.13 to 0.65, P = 0.001; and overall survival: HR = 0.28, 95% CI, 0.10 to 0.76, P = 0.008). HER2 amplification seems to drive genomic instability along chromosome 17q, leading to different patterns of gene amplification. This study confirms the clinical importance of identifying, among patients with HER2-positive breast tumors, the subgroup of patients with hormone receptor-negative and nonamplified TOP2A cancers as they have the worst prognosis.


Stem cell secretome attenuates acute rejection in rat lung allotransplant.
Stem cells secrete significant amounts of bioactive factors in their secretome that can be immunosuppressive. We studied the effect of the secretome obtained from bone marrow-derived mesenchymal stem cells (BMSC-sec) in combination with cyclosporine A following acute rejection of lung allografts in the rat. Lung allotransplants were performed from male Brown Norway donor rats to recipient male Fisher 344 rats. Rat BMSC-sec was introduced intratracheally in the recipient every day after the transplant until the day the animal was sacrificed. Group A (n = 5) received control medium and cyclosporine A (2.5 mg/kg body weight intraperitoneally) for 5 days post-transplant and group B (n = 5) received BMSC-sec and cyclosporine A. Blood gas analysis was performed to assess graft function at day 5 only from the graft, and the tissue was sampled for measurement of the wet/dry ratio and histological grading of rejection. All control animals (group A) showed severe signs of rejection. At day 5 grafts in group B showed improved gas exchange (i.e. mean PaO2 mmHg 237.9 ± 130 mmHg vs 24.9 ± 7.8 mmHg in group A). Histological examination according to the International Society of Heart and Lung Transplantation (ISHLT) revealed moderate to severe rejection in all animals in group A (III B) and a significant improvement in group B (I-IIA). The wet/dry ratio was also reduced in group B to 6.19 ± 0.6 compared to 9.36 ± 2 in group A. Furthermore, in vitro T-cell proliferation was reduced after treatment with BMSC-sec for CD 3 cells (69.55 ± 07 vs 73 ± 0.84), for CD 4 (24.95 ± 1.2 vs 27.75 ± 0.21) and for CD 8 cells (3.75 ± 0.2 vs 5.68 ± 0.02). The BMSC-sec is a promising novel cell-based therapeutic option for acute rejection in a rat lung allograft model.


Polymorphisms in maternal and fetal genes encoding for proteins involved in extracellular matrix metabolism alter the risk for small-for-gestational-age.
To examine the association between maternal and fetal genetic variants and small-for-gestational-age (SGA). A case-control study was conducted in patients with SGA neonates (530 maternal and 436 fetal) and controls (599 maternal and 628 fetal); 190 candidate genes and 775 SNPs were studied. Single-locus, multi-locus and haplotype association analyses were performed on maternal and fetal data with logistic regression, multifactor dimensionality reduction (MDR) analysis, and haplotype-based association with 2 and 3 marker sliding windows, respectively. Ingenuity pathway analysis (IPA) software was used to assess pathways that associate with SGA. The most significant single-locus association in maternal data was with a SNP in tissue inhibitor of metalloproteinase 2 (TIMP2) (rs2277698 OR = 1.71, 95% CI [1.26-2.32], p = 0.0006) while in the fetus it was with a SNP in fibronectin 1 isoform 3 preproprotein (FN1) (rs3796123, OR = 1.46, 95% CI [1.20-1.78], p = 0.0001). Both SNPs were adjusted for potential confounders (maternal body mass index and fetal sex). Haplotype analyses resulted in associations in α 1 type I collagen preproprotein (COL1A1, rs1007086-rs2141279-rs17639446, global p = 0.006) in mothers and FN1 (rs2304573-rs1250204-rs1250215, global p = 0.045) in fetuses. Multi-locus analyses with MDR identified a two SNP model with maternal variants collagen type V α 2 (COL5A2) and plasminogen activator urokinase (PLAU) predicting SGA outcome correctly 59% of the time (p = 0.035). Genetic variants in extracellular matrix-related genes showed significant single-locus association with SGA. These data are consistent with other studies that have observed elevated circulating fibronectin concentrations in association with increased risk of SGA. The present study supports the hypothesis that DNA variants can partially explain the risk of SGA in a cohort of Hispanic women.


Halioglobus sediminis sp. nov., isolated from coastal sediment.
A novel aerobic, Gram-stain-negative, non-motile and rod-shaped bacterium, designated strain U0301T, was isolated from a marine sediment sample in Weihai, China. This strain grew optimally at 33 °C, pH 7.5 and in the presence of 2.0-3.0 % (w/v) NaCl. Strain U0301T shared pairwise 16S rRNA gene sequence similarities of 95.5, 95.4, 95.2 and 95.0 % to Parahaliea aestuarii S2-26T, Halioglobus pacificus KCTC 23430T, Halioglobus lutimaris HF004T and Halioglobus japonicus KCTC 23429T, respectively. Phylogenetic analysis based on the 16S rRNA gene sequences demonstrated that U0301T formed a tight phylogenetic lineage with type strains of H. pacificus and H. japonicus. The percentage of conserved protein values of strain U0301T as compared with H. japonicus KCTC 23429Tand Parahalieamediterranea 7SM29T were 62.5 and 58.0 %, respectively. The ANI values of strain U0301T with H. japonicus KCTC 23429T and P. mediterranea 7SM29T were 78.2 and 75.3 %, respectively. Both metrics of genome comparison suggested that strain U0301T showed higher homology with the genus Halioglobus than the genus Parahaliea. The strain contained ubiquinone 8 as the sole respiratory quinone. The major fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) and C17 : 1ω8c. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The DNA G+C content was 61.7 mol%. Considering the phenotypic characteristics, chemotaxonomic data and phylogenetic analysis comprehensively, strain U0301T should represent a novel species of the genus Halioglobus, for which the name of Halioglobus sediminis sp. nov. is proposed. The type strain is U0301T (=KCTC 62082T=MCCC 1H00234T).


Oncology care in rural northern new England.
A team from Maine, New Hampshire, and Vermont evaluated quality of care for breast and colon cancers in these predominantly rural states. Central cancer registry records from diagnosis years 2003 to 2004 in Maine, New Hampshire, and Vermont were aggregated. Patient residence was classified into three tiers (small rural, large rural, and urban) using Rural-Urban Commuting Area classification. Among 6,134 women diagnosed with breast cancer, there were significant differences between rural and urban residents in age (P < .001), stage (P < .001), and tumor size (P = .006). Use of breast-conserving surgery was similar, but sentinel lymph node (SLN) dissection was more common in urban (44.1%) than in large rural (39.9%) and small rural (37.6%) areas. Patients who underwent SLN dissection were more likely to receive radiation therapy after lumpectomy than patients who underwent regional lymph node dissection without SLN (85.9% v 75.5%). However, there was no statistically significant association between the rates of postlumpectomy radiation therapy by residence. Among 2,848 patients with colon cancer, patient characteristics in rural and urban areas were similar, but there were differences in their subsequent surgical treatment (P < .001) and lymph node sampling (P = .079). Adjuvant chemotherapy for patients with stage III colon cancer was less frequent in rural (57.3%) than in urban areas (64.7%; P < .001). Central cancer registry data, aggregated among three states, identified differences between rural and urban areas in care for patients with breast and colon cancers. To our knowledge, this is the first time residential category, cancer stage, and treatment data have been analyzed for multiple states using population-based data.


Clinical trials in the gene therapy of arthritis.
Gene therapy clinical trials raise important safety issues that complicate their design and require extensive preclinical testing. Human protocols for the treatment of arthritis and most other orthopaedic and rheumatologic indications are complicated additionally by the perception that they are largely acquired, nonlethal conditions. Taking these considerations into account, the first such human study used the local, ex vivo delivery of a gene whose product, the interleukin-1 receptor antagonist, has an outstanding safety profile. This gene was delivered to the metacarpophalangeal joints of postmenopausal women 1 week before these joints were removed during total joint replacement surgery. In addition to providing an additional safety cushion, the surgical removal of the genetically modified joints made available large amounts of tissue to examine for evidence of successful gene transfer and gene expression. This Phase I safety study was approved at the local and federal levels, and its funding was contingent on the establishment of an external monitoring board. This trial now has been completed and a Phase II, efficacy study is being planned. A similar study has begun in Dusseldorf, Germany and results from the first two patients are similar to the results of the American patients. Permission has been given for two additional human trials, one in the United States and one in the Netherlands, in which a gene encoding herpes thymidine kinase will be transferred to the joints of patients with rheumatoid arthritis who then will be administered gancyclovir. This procedure aims to treat the disease by producing a genetic synovectomy. Additional development of human gene therapies for arthritis and other orthopaedic and rheumatic conditions will be aided by the successful completion of these studies.


DNA immunization confers protection against murine cytomegalovirus infection.
The murine cytomegalovirus (MCMV) immediate-early gene 1 (IE1) encodes an 89-kDa phosphoprotein (pp89) which plays a key role in protecting BALB/c mice against the lethal effects of the MCMV infection. In this report, we have addressed the question of whether "naked DNA" vaccination with a eukaryotic expression vector (pcDNA-89) that contains the MCMV IE1 gene driven by a strong enhancer/promoter can confer protection. BALB/c mice were immunized intradermally with pcDNA-89 or with the plasmid backbone pcDNAI/Amp (pcDNA) and then challenged 2 weeks later with either a lethal or a sublethal intraperitoneal dose of the K181 strain of MCMV. Variable results were obtained for the individual experiments in which mice received a lethal challenge. In four separate trials, an average of 63% of the mice immunized with pcDNA-89 survived, compared with 18% of the mice immunized with pcDNA. However, in two other trials there was no specific protection. The results of experiments in which mice were injected with a sublethal dose of MCMV were more consistent, and significant decreases in viral titer in the spleen and salivary glands of pcDNA-89-immunized mice were observed, relative to controls. At the time of peak viral replication, titers in the spleens of immunized mice were reduced 18- to >63-fold, while those in the salivary gland were reduced approximately 24- to 48-fold. Although DNA immunization elicited only a low level of seroconversion in these mice, by 7 weeks postimmunization the mice had generated a cytotoxic T-lymphocyte response against pp89. These results suggest that DNA vaccination with selected CMV genes may provide a safe and efficient means of immunizing against CMV disease.


Quantization error of CCD cameras and their influence on phase calculation in fringe pattern analysis.
We present an investigation into the phase errors that occur in fringe pattern analysis that are caused by quantization effects. When acquisition devices with a limited value of camera bit depth are used, there are a limited number of quantization levels available to record the signal. This may adversely affect the recorded signal and adds a potential source of instrumental error to the measurement system. Quantization effects also determine the accuracy that may be achieved by acquisition devices in a measurement system. We used the Fourier fringe analysis measurement technique. However, the principles can be applied equally well for other phase measuring techniques to yield a phase error distribution that is caused by the camera bit depth.


Viscosities of implantable biomaterials in vocal fold augmentation surgery.
Vocal fold vibration depends critically on the viscoelasticity of vocal fold tissues. For instance, phonation threshold pressure, a measure of the "ease" of phonation, has been shown to be directly related to the viscosity of the vibrating mucosa. Various implantable biomaterials have been used in vocal fold augmentation surgery, with implantation sites sometimes close to or inside the mucosa. Yet their viscosities or other mechanical properties are seldom known. This study attempts to provide data on viscosities of commonly used phonosurgical biomaterials. Using a parallel-plate rotational rheometer, oscillatory shear experiments were performed on implantable polytetrafluoroethylene (Teflon or Polytef; Mentor Inc., Hingham, MA), collagen (Zyderm; Collagen Corp., Palo Alto, CA), glutaraldehyde crosslinked (GAX) collagen (Phonagel or Zyplast; Collagen Corp.), absorbable gelatin (Gelfoam; Upjohn Co., Kalamazoo, MI), and human abdominal subcutaneous fat. Samples of human vocal fold mucosal tissues were also tested. Under sinusoidal oscillatory shear at 10 Hz and at 37 degrees C, the dynamic viscosity was 116 Pascal-seconds (Pa-s) for polytetrafluoroethylene, 21 Pa-s for gelatin, 8-13 Pa-s for the two types of collagen, 3 Pa-s for fat, and 1 to 3 Pa-s for vocal fold mucosa. Results extrapolated to 100 Hz also show similar differences among the biomaterials, but all values are an order of magnitude lower because of the typical inverse frequency relation (shear thinning effect) for polymeric and biologic materials. The data suggest that the use of fat for vocal fold augmentation may be more conducive to the "ease" of phonation because of its relatively low viscosity, which is closest to physiologic levels. This implication is probably the most relevant in predicting initial outcome of the postoperative voice before there is any significant assimilation (e.g., resorption and fibrosis) of the implanted biomaterial.


Which phantom is better for assessing the image quality in full-field digital mammography?: American College of Radiology Accreditation phantom versus digital mammography accreditation phantom.
To compare between the American College of Radiology (ACR) accreditation phantom and digital mammography accreditation phantom in assessing the image quality in full-field digital mammography (FFDM). In each week throughout the 42-week study, we obtained phantom images using both the ACR accreditation phantom and the digital mammography accreditation phantom, and a total of 42 pairs of images were included in this study. We assessed the signal-to-noise ratio (SNR) in each phantom image. A radiologist drew a square-shaped region of interest on the phantom and then the mean value of the SNR and the standard deviation were automatically provided on a monitor. SNR was calculated by an equation, measured mean value of SNR-constant coefficient of FFDM/standard deviation. Two breast radiologists scored visible objects (fibers, specks, and masses) with soft-copy images and calculated the visible rate (number of visible objects/total number of objects). We compared SNR and the visible rate of objects between the two phantoms and calculated the k-coefficient for interobserver agreement. The SNR of the ACR accreditation phantom ranged from 42.0 to 52.9 (Mean, 47.3 ± 2.79) and that of Digital Phantom ranged from 24.8 to 54.0 (Mean, 44.1 ± 9.93) (p = 0.028). The visible rates of all three types of objects were much higher in the ACR accreditation phantom than those in the digital mammography accreditation phantom (p < 0.05). Interobserver agreement for visible rates of objects on phantom images was fair to moderate agreement (k-coefficients: 0.34-0.57). The ACR accreditation phantom is superior to the digital mammography accreditation phantom in terms of SNR and visibility of phantom objects. Thus, ACR accreditation phantom appears to be satisfactory for assessing the image quality in FFDM.


Prevalence of antibody to human T cell lymphotropic virus types 1/2 among aboriginal groups inhabiting northern Argentina and the Amazon region of Peru.
We carried out a seroepidemiologic survey to define the prevalence of human T cell lymphotropic virus types 1/2 (HTLV-1/2) infections among aboriginal populations from isolated regions of northern Argentina and the Amazon region of Peru. Antibodies against HTLV were measured with agglutination tests and confirmed with by an immunofluorescence assay (IFA) and Western blotting. Five (6.94%) of 72 samples from the Tobas Indians in Argentina were positive by the IFA; two samples were typed as HTLV-1 (2.78%), two as HTLV-2 (2.78%), and one (1.39%) could not be typed because it had similar antibody titers against both viruses. No positive samples were found among 84 Andinos Puneños and 47 Matacos Wichis Indians. Seroprevalences of 2.50% (1 of 40) and 1.43% (1 of 70) for HTLV-1 were observed among Wayku and San Francisco communities in the Amazon region of Peru, and seroprevalences of 4.54% (1 of 22) and 2.38% (1 of 42) for HTLV-2 were observed among Boca Colorada and Galilea communities. No serologic evidence of human immunodeficiency virus (HIV) infection was found among the Indians tested. These results indicated the presence of HTLV-1 and HTLV-2 in the indigenous populations of Argentina and Peru. Moreover, the lack of HIV infection indicates that the virus has probably not yet been introduced into these populations.


MicroRNA-gene expression network in murine liver during Schistosoma japonicum infection.
Schistosomiasis japonica remains a significant public health problem in China and Southeast Asian countries. The most typical and serious outcome of the chronic oriental schistosomiasis is the progressive granuloma and fibrosis in the host liver, which has been a major medical challenge. However, the molecular mechanism underling the hepatic pathogenesis is still not clear. Using microarrays, we quantified the temporal gene expression profiles in the liver of Schistosoma japonicum-infected BALB/c mice at 15, 30, and 45 day post infection (dpi) with that from uninfected mice as controls. Gene expression alternation associated with liver damage was observed in the initial phase of infection (dpi 15), which became more magnificent with the onset of egg-laying. Up-regulated genes were dominantly associated with inflammatory infiltration, whereas down-regulated genes primarily led to the hepatic functional disorders. Simultaneously, microRNA profiles from the same samples were decoded by Solexa sequencing. More than 130 miRNAs were differentially expressed in murine liver during S. japonicum infection. MiRNAs significantly dysregulated in the mid-phase of infection (dpi 30), such as mmu-miR-146b and mmu-miR-155, may relate to the regulation of hepatic inflammatory responses, whereas miRNAs exhibiting a peak expression in the late phase of infection (dpi 45), such as mmu-miR-223, mmu-miR-146a/b, mmu-miR-155, mmu-miR-34c, mmu-miR-199, and mmu-miR-134, may represent a molecular signature of the development of schistosomal hepatopathy. Further, a dynamic miRNA-gene co-expression network in the progression of infection was constructed. This study presents a global view of dynamic expression of both mRNA and miRNA transcripts in murine liver during S. japonicum infection, and highlights that miRNAs may play a variety of regulatory roles in balancing the immune responses during the development of hepatic pathology. The data provide robust information for further researches on the pathogenesis and molecular events of hepatopathy induced by schistosome eggs.


Divergent Synthesis and Real-Time Biological Annotation of Optically Active Tetrahydrocyclopenta[c]pyranone Derivatives.
Sp3-rich compounds are underrepresented in libraries for probe- and drug-discovery, despite their promise of extending the range of accessible molecular shapes beyond planar geometries. With this in mind, a collection of single-enantiomer bicyclic, fused cyclopentenones underpinned by a complexity-generating Pauson-Khand cyclization was synthesized. A fingerprint of biological actions of these compounds was determined immediately after synthesis using real-time annotation-a process relying on multiplexed measurements of alterations in cell morphological features.


Influence of cyanobacteria on water activity and dry matter of muscles in the common carp (Cyprinus carpio L.) and rainbow trout (Oncorhynchus mykiss W.).
Cyanobacteria are studied from the viewpoint of the issue of risks to water supply, agriculture and recreational activities for a long time. Cyanobacteria produce a wide range of substances which can be toxic and can influence the safety and quality of fish products. The aim of this study was to determine whether the diet with the content of cyanobacteria can affect the water activity and the dry matter of fish muscle and whether this diet can contribute significantly to the shelf life of fish muscles. Common carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss) were used in this study. Both fish species were divided into two groups. The first group of fish was fed with feed with cyanobacteria (3% of dry matter), the second group with feed without cyanobacteria. The water activity and the dry matter were monitored immediately after sampling of the fish muscle on day 7, 14 and 21 (carp) or on day 10, 20 and 30 (rainbow trout) and seven days after every sampling and cold storage (6-8 °C). Feed with the content of cyanobacteria significantly decreased the water activity in muscles of both fish species on day 21 (in carp) and on day 30 (in rainbow trout). The dry matter of fish muscle significantly increased on day 7 and 21 (in carp) and on day 10 and 30, but decreased on day 20 (in rainbow trout). The cold storage significantly influenced the dry matter only. While the dry matter was increased in the common carp (7 days of cold storage after sampling on days 14 and 21), the dry matter decreased in the rainbow trout (7 days of cold storage after sampling on day 10). The decrease of water activity was found only after longer exposure in the both exposed fish species. The dry matter was influenced far greater and was mostly increased in the both exposed fish species.