Bicompartmental Knee Arthroplasty.
Knee arthritis is one of the leading causes of disability and functional limitations in the United States and worldwide. Total knee arthroplasty results in good functional outcomes and high survival rates in patients who have tricompartmental arthritis. Bicompartmental knee arthroplasty is being used more often in patients who have arthritis that is isolated to two compartments: the patellofemoral compartment and either the medial or the lateral compartment. Bicompartmental knee arthroplasty preserves the kinematics, ligaments, and bone stock of the knee and is a good option for younger, active, high-demand patients who wish to return to their previous level of activity.


Analysis of peripheral arterial bends that interfere with coronary catheterization.
The aim of this study was to analyze the characteristics of peripheral arterial bends that interfere with coronary catheterization. Complex aortic and peripheral arterial bends are important factors in unsuccessful coronary catheterization. Methods.We classified peripheral arterial bends based on the difficulty of coronary catheterization: no bend, type A: easy; type B1: difficult but possible; type B2: difficult but possible with assistance of a device such as a long sheath; type C: impossible. We analyzed 1,626 consecutive cardiac catheterizations. Reproducibility (+/- 1 grade) was 98.9% in 256 patients undergoing multiple procedures from the same approach site. Peripheral arterial bend class distribution was as follows: no bend: 76.4%, type A: 12.5%, type B1: 5.0%, type B2: 5.5%, and type C: 0.6%. Fluoroscopy time and contrast volume were significantly greater in type B2/C (9.6 +/- 6.26 min versus 13.8 +/- 8.9 min, p < 0.0001 and 142.0 +/- 38.8 ml versus 168.4 +/- 53.6 ml, p < 0.0001, respectively). There were no differences in the distribution of types B and C by approach site; femoral approach, 6.4%% right upper limb approach, 6.1%; and left upper limb approach, 5.0%. Furthermore, in the patients who underwent multiple catheterizations from different approach sites, the arterial bend classes were similar. Predictors of a type B2/C arterial bend were mainly atherosclerotic risk factors, suggesting that longitudinal arterial elongation is the major cause of arterial bends. Peripheral arterial bends are a feature of the individual patient, not of the approach site.


Aggregation and contingent metal/surface reactivity of 1,3,8,10-tetraazaperopyrene (TAPP) on Cu(111).
The structural chemistry and reactivity of 1,3,8,10-tetraazaperopyrene (TAPP) on Cu(111) under ultra-high-vacuum (UHV) conditions has been studied by a combination of experimental techniques (scanning tunneling microscopy (STM) and X-ray photoelectron spectroscopy, XPS) and DFT calculations. Depending on the deposition conditions, TAPP forms three main assemblies, which result from initial submonolayer coverages based on different intermolecular interactions: a close-packed assembly similar to a projection of the bulk structure of TAPP, in which the molecules interact mainly through van der Waals (vDW) forces and weak hydrogen bonds; a porous copper surface coordination network; and covalently linked molecular chains. The Cu substrate is of crucial importance in determining the structures of the aggregates and available reaction channels on the surface, both in the formation of the porous network for which it provides the Cu atoms for surface metal coordination and in the covalent coupling of the TAPP molecules at elevated temperature. Apart from their role in the kinetics of surface transformations, the available metal adatoms may also profoundly influence the thermodynamics of transformations by coordination to the reaction product, as shown in this work for the case of the Cu-decorated covalent poly(TAPP-Cu) chains.


Yeast--a panacea for the structure-function analysis of membrane proteins?
In recent years, the scientific community has begun to realise that the structure-function analysis of membrane proteins has lagged considerably behind that of their soluble counterparts. A boom in the field of membrane protein biology has resulted in the tailoring of techniques for the cloning, expression, purification and characterisation of these somewhat intractable proteins and most notably in the optimisation of several alternative host systems for this purpose. This Review Article summarises the use of yeast as a host. Compared with other hosts, it is clear that yeast combines the advantages of eukaryotes with the ease of handling of prokaryotes. Moreover, this organism provides membrane protein biologists with a panacea for structure-function analyses, not least because the tools of yeast genetics are at their disposal.


Towards a political ontology of state power: a comment on Colin Hay's article.
This article offers some critical realist, strategic-relational comments on Colin Hay's proposal to treat the state as an 'as-if-real' concept. The critique first develops an alternative account of ontology, which is more suited to analyses of the state and state power; it then distinguishes the 'intransitive' properties of the real world as an object of investigation from the 'transitive' features of its scientific investigation and thereby provides a clearer understanding of what is at stake in 'as-if-realism'; and it ends with the suggestion that a concern with the modalities of state power rather than with the state per se offers a more fruitful approach to the genuine issues raised in Hay's article and in his earlier strategic-relational contributions to political analysis.


International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients.
A century after its discovery, Chagas disease still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The purpose of this study was to evaluate the performance of PCR methods in detection of Trypanosoma cruzi DNA by an external quality evaluation. An international collaborative study was launched by expert PCR laboratories from 16 countries. Currently used strategies were challenged against serial dilutions of purified DNA from stocks representing T. cruzi discrete typing units (DTU) I, IV and VI (set A), human blood spiked with parasite cells (set B) and Guanidine Hidrochloride-EDTA blood samples from 32 seropositive and 10 seronegative patients from Southern Cone countries (set C). Forty eight PCR tests were reported for set A and 44 for sets B and C; 28 targeted minicircle DNA (kDNA), 13 satellite DNA (Sat-DNA) and the remainder low copy number sequences. In set A, commercial master mixes and Sat-DNA Real Time PCR showed better specificity, but kDNA-PCR was more sensitive to detect DTU I DNA. In set B, commercial DNA extraction kits presented better specificity than solvent extraction protocols. Sat-DNA PCR tests had higher specificity, with sensitivities of 0.05-0.5 parasites/mL whereas specific kDNA tests detected 5.10(-3) par/mL. Sixteen specific and coherent methods had a Good Performance in both sets A and B (10 fg/µl of DNA from all stocks, 5 par/mL spiked blood). The median values of sensitivities, specificities and accuracies obtained in testing the Set C samples with the 16 tests determined to be good performing by analyzing Sets A and B samples varied considerably. Out of them, four methods depicted the best performing parameters in all three sets of samples, detecting at least 10 fg/µl for each DNA stock, 0.5 par/mL and a sensitivity between 83.3-94.4%, specificity of 85-95%, accuracy of 86.8-89.5% and kappa index of 0.7-0.8 compared to consensus PCR reports of the 16 good performing tests and 63-69%, 100%, 71.4-76.2% and 0.4-0.5, respectively compared to serodiagnosis. Method LbD2 used solvent extraction followed by Sybr-Green based Real time PCR targeted to Sat-DNA; method LbD3 used solvent DNA extraction followed by conventional PCR targeted to Sat-DNA. The third method (LbF1) used glass fiber column based DNA extraction followed by TaqMan Real Time PCR targeted to Sat-DNA (cruzi 1/cruzi 2 and cruzi 3 TaqMan probe) and the fourth method (LbQ) used solvent DNA extraction followed by conventional hot-start PCR targeted to kDNA (primer pairs 121/122). These four methods were further evaluated at the coordinating laboratory in a subset of human blood samples, confirming the performance obtained by the participating laboratories. This study represents a first crucial step towards international validation of PCR procedures for detection of T. cruzi in human blood samples.


Automatic classification of medical image modality and anatomical location using convolutional neural network.
Modern radiologic images comply with DICOM (digital imaging and communications in medicine) standard, which, upon conversion to other image format, would lose its image detail and information such as patient demographics or type of image modality that DICOM format carries. As there is a growing interest in using large amount of image data for research purpose and acquisition of large amount of medical image is now a standard practice in the clinical setting, efficient handling and storage of large amount of image data is important in both the clinical and research setting. In this study, four classes of images were created, namely, CT (computed tomography) of abdomen, CT of brain, MRI (magnetic resonance imaging) of brain and MRI of spine. After converting these images into JPEG (Joint Photographic Experts Group) format, our proposed CNN architecture could automatically classify these 4 groups of medical images by both their image modality and anatomic location. We achieved excellent overall classification accuracy in both validation and test sets (> 99.5%), specificity and F1 score (> 99%) in each category of this dataset which contained both diseased and normal images. Our study has shown that using CNN for medical image classification is a promising methodology and could work on non-DICOM images, which could potentially save image processing time and storage space.


Human and Nonhuman Primate Lineage-Specific Footprints in the Salivary Proteome.
Proteins in saliva are needed for preprocessing food in the mouth, maintenance of tooth mineralization, and protection from microbial pathogens. Novel insights into human lineage-specific functions of salivary proteins and clues to their involvement in human disease can be gained through evolutionary studies, as recently shown for salivary amylase AMY1 and salivary agglutinin DMBT1/gp340. However, the entirety of proteins in saliva, the salivary proteome, has not yet been investigated from an evolutionary perspective. Here, we compared the proteomes of human saliva and the saliva of our closest extant evolutionary relatives, chimpanzees and gorillas, using macaques as an outgroup, with the aim to uncover features in saliva protein composition that are unique to each species. We found that humans produce a waterier saliva, containing less than half total protein than great apes and Old World monkeys. For all major salivary proteins in humans, we could identify counterparts in chimpanzee and gorilla saliva. However, we discovered unique protein profiles in saliva of humans that were distinct from those of nonhuman primates. These findings open up the possibility that dietary differences and pathogenic pressures may have shaped a distinct salivary proteome in the human lineage.


A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis.
Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intra-individual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available.


Understanding spitzoid tumours: new insights from molecular pathology.
Spitzoid tumours are a morphologically diverse group of lesions that share histological similarity to the Spitz naevus, a benign melanocytic skin tumour. Distinguishing classic Spitz naevi from cutaneous malignant melanoma is usually achievable on standard histology sections, but occasionally equivocal lesions are encountered that show features intermediate between these two entities and consequently generate considerable clinical and histopathological concern. The nomenclature and diagnostic criteria for spitzoid lesions are not standardized and this article begins by considering the adverse effect this has on our understanding of spitzoid tumour biology. Investigations of some of the hallmark features of cancer and neoplasia in spitzoid tumours are described, and the contribution of these studies to our understanding of spitzoid tumour biology is considered, along with their potential diagnostic utility. These studies compare spitzoid tumours with better-characterized melanocytic lesions, and from such comparisons assumptions concerning the biological nature of different spitzoid tumours can be made. In contrast, investigations of the mitogen-activated protein kinase (MAPK) pathway and DNA gains and losses have suggested that Spitz naevi may be genetically distinct from other melanocytic tumours. The studies that led to this conclusion are reviewed, as well as subsequent work examining whether the same applies to all spitzoid tumours. Possible explanations for the considerable inconsistencies within some of these data are explored. Finally, potential pathways of tumour progression within spitzoid lesions are considered, with an emphasis placed upon insights gained from investigations of MAPK genes and DNA gains and losses.


The limbic circuitry underlying cocaine seeking encompasses the PPTg/LDT.
The direct glutamatergic projection from the medial prefrontal cortex (mPFC) to the nucleus accumbens plays a critical role in mediating the reinstatement of cocaine seeking behavior. The mPFC also sends glutamatergic projections to the pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDT), which in turn send glutamatergic and cholinergic efferents to the ventral tegmental area (VTA) where they synapse on dopaminergic cells that innervate limbic structures including the nucleus accumbens. The goal of these experiments was to examine a potential role for the PPTg/LDT in the reinstatement of cocaine seeking. All rats were trained to self-administer cocaine (0.25 mg, i.v.) on a fixed-ratio 5 schedule of reinforcement. Cocaine self-administration behavior was extinguished and a series of subsequent pharmacological experiments were performed to assess the potential role of the mPFC, PPTg/LDT and VTA in the reinstatement of cocaine seeking. Administration of the D1-like dopamine receptor agonist SKF-81297 (1.0 microg) directly into the mPFC produced a small, but statistically significant, increase in cocaine seeking behavior. Furthermore, microinjection of the ionotropic glutamate receptor antagonist CNQX (0.3 microg) into the PPTg/LDT attenuated the reinstatement of drug seeking induced by a priming injection of cocaine (10 mg/kg, i.p.). Intra-VTA administration of CNQX, the nicotinic receptor antagonist mecamylamine (10.0 microg) or the muscarinic receptor antagonist scopolamine (24.0 microg) also blocked cocaine seeking. Taken together, these results suggest that cocaine priming-induced reinstatement of drug seeking is mediated in part by a serial polysynaptic limbic subcircuit encompassing the mPFC, PPTg/LDT and VTA.


Leaky gut and diabetes mellitus: what is the link?
Diabetes mellitus is a chronic disease requiring lifelong medical attention. With hundreds of millions suffering worldwide, and a rapidly rising incidence, diabetes mellitus poses a great burden on healthcare systems. Recent studies investigating the underlying mechanisms involved in disease development in diabetes point to the role of the dys-regulation of the intestinal barrier. Via alterations in the intestinal permeability, intestinal barrier function becomes compromised whereby access of infectious agents and dietary antigens to mucosal immune elements is facilitated, which may eventually lead to immune reactions with damage to pancreatic beta cells and can lead to increased cytokine production with consequent insulin resistance. Understanding the factors regulating the intestinal barrier function will provide important insight into the interactions between luminal antigens and immune response elements. This review analyses recent advances in the mechanistic understanding of the role of the intestinal epithelial barrier function in the development of type 1 and type 2 diabetes. Given our current knowledge, we may assume that reinforcing the intestinal barrier can offer and open new therapeutic horizons in the treatment of type 1 and type 2 diabetes.


Simultaneous removal of rotavirus and adenovirus from artificial ground water using hydrochar derived from swine feces.
Hydrothermal carbonization technology can convert fecal waste into a valuable carbonaceous product referred to as hydrochar. We investigated the potential of fecal waste-derived hydrochar as an adsorbent for virus removal in water treatment. Swine feces was hydrothermally treated under two conditions: at 180 °C for 2 h and 230 °C for 7 h. The resulting solid products (hydrochar) were evaluated as virus adsorbents in water treatment. Simultaneous removal of pathogenic rotavirus (RV) and human adenovirus (HAdV) was investigated using a sand column set-up of 10 cm bed height with and without hydrochar supplement (1.5%, w/w). The removal efficiency of both viruses in a hydrochar-amended column was >3 log (complete removal). The amount of virus released in deionized water when flushed into the virus-retaining columns indicated that the secondary energy minimum played a more important role in RV retention than that of HAdV. Zeta-potential and hydrophobicity measurements on hydrochar materials indicated that the improved virus removal performance of hydrochar-amended columns was induced by the provision of extra hydrophobic surfaces. This study provides evidence that fecal waste-derived hydrochar can be used as a competent virus adsorbent.


Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes.
Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, show a limited amino acid sequence divergence. Their embryonic expression patterns overlap in spatial and temporal profiles with two major exceptions: until 8 days post coitum (d.p.c. ) only Otx2 is expressed in gastrulating embryos, and from 11 d.p.c. onwards only Otx1 is transcribed within the dorsal telencephalon. Otx1 null mice exhibit spontaneous epileptic seizures and multiple abnormalities affecting primarily the dorsal telencephalic cortex and components of the acoustic and visual sense organs. Otx2 null mice show heavy gastrulation abnormalities and lack the rostral neuroectoderm corresponding to the forebrain, midbrain and rostral hindbrain. In order to define whether these contrasting phenotypes reflect differences in expression pattern or coding sequence of Otx1 and Otx2 genes, we replaced Otx1 with a human Otx2 (hOtx2) full-coding cDNA. Interestingly, homozygous mutant mice (hOtx2(1)/hOtx2(1)) fully rescued epilepsy and corticogenesis abnormalities and showed a significant improvement of mesencephalon, cerebellum, eye and lachrymal gland defects. In contrast, the lateral semicircular canal of the inner ear was never recovered, strongly supporting an Otx1-specific requirement for the specification of this structure. These data indicate an extended functional homology between OTX1 and OTX2 proteins and provide evidence that, with the exception of the inner ear, in Otx1 and Otx2 null mice contrasting phenotypes stem from differences in expression patterns rather than in amino acid sequences.


Polyomavirus large T antigen is prevalent in urothelial carcinoma post-kidney transplant.
Viral pathogens have been associated with both infectious disease and neoplasia in transplant recipients. Polyomavirus is emerging as a potential causative agent for genitourinary tract cancer in post-kidney transplant patients. Human papillomavirus (HPV) has a proven role in squamous cancers, but has not been studied in genitourinary malignancies in transplantation. Of 2345 kidney transplants performed at our center over the past 20 years, we identified 16 patients with 20 genitourinary cancers (0.7%), including 13 bladder/ureter carcinomas, 5 renal cell carcinomas (RCCs), and 2 prostate carcinomas. We performed immunohistochemical staining for polyomavirus large T antigen and p16, followed by in situ hybridization for HPV in p16+ cases. Four cases of high-grade invasive urothelial bladder carcinomas were positive for large T. Large T+ urothelial carcinomas developed at least 8 years posttransplant in young men, 3 with history of BK polyoma viremia, 2 of whom had native kidney failure due to reflux/obstruction. In situ hybridization for high-risk HPV was negative in all tested cases. Overall, 3 patients died of carcinoma. All 5 RCCs were negative for both large T and p16; 2 prostate cancers were p16 negative and p16+/HPV negative, respectively. Thus, our study shows a relatively high prevalence of large T antigen in urothelial carcinoma in kidney transplant patients (31%), but not in RCC. Although sample size is small, young patients with obstructive disease may be at particular risk for developing large T-positive urothelial carcinoma. Overall, our data further support the necessities of long-term cancer surveillance for renal transplant patients.


Medicinal plants in the southern region of the State of Nuevo León, México.
Although the flora of the State of Nuevo León is well known, there are few records of ethnobotancial information. An ethnobotanical study was undertaken in order to know the medicinal plants used by people living at the scrublands and oak-pine forest areas in the southern Nuevo León. Collection of plants specimens and interviews were carried out among the people of the municipalities of Aramberri, Galeana, and Zaragoza. Since former studies in the region are scarce, the aim of this work was to record the medicinal species and their uses in the scrublands and oak-pine forest areas, of southern Nuevo León, Mexico, and also to know if there are differences in the number of species and number of uses knowledge by people. Field work was carried out over a 2 years period; useful plants were collected and a total of 105 people from 46 different villages were interviewed. A database was compiled using data collected by means of semi structured interviews. The data were analyzed by means of non-parametric statistics, using goodness-of-fit test (Chi-squared) (number of species known by people of each municipality, number of uses known by people of each municipality), Chi-squared modified to incorporate the Yates Correction (number of species known by people living at scrublands and oak-pine forest); the Kruskall-Wallis test (number of species known by women and men of the three municipalities), and the Spearman's rank correlation coefficient (age and number of species known, and age and number of uses). A total of 163 medicinal plant species were recorded in the study area, comprising 108 wild and 55 cultivated plants. A total of 117 species were recorded in the oak-pine forest, and 111 in the scrublands area, a total of 68 were recorded in both areas; 68 medicinal species are used in all three municipalities, 40 wild and 28 cultivated. We documented 235 different medicinal uses. The most common plant parts used for medicinal purposes were found to be leaves (123 species), stems (55), fruits (28), roots (17), and bark (14). No differences were noted in the number of medicinal plant species identified among people, but differences were significant in their knowledge with respect to the number of uses among people of the three municipalities studied; people from both, scrublands and oak-pine forest know similar number of species and number of uses. Men and women of the three different municipalities knew statistically the same number of species and number of uses. There was no correlation between resident's age and number of species known and resident's age and number of uses either in Galeana or in Aramberri, but, there was high correlation among these variables in Zaragoza. In southern Nuevo León people use at least 5% of the total State flora as medicinal plants, and most of these species are included in few plant families. Most of medicinal species are wild and indigenous to the region. The two most important major plant communities, scrublands and oak-pine forest provide almost the same number of medicinal species. A third of the medicinal flora recorded are used in all three municipalities, most of them are wild. Leaves, stems and fruits are the plant parts most commonly used for healing, and boiling is the most common method used for this purpose. Men and women from the three municipalities are familiar with nearly the same number of species; however, their knowledge of the number of uses varies significantly. In Galeana and Aramberri there was no correlation between a person's age and number of species recognized, however, in Zaragoza, there existed a high correlation between these two factors.


Comparison of early postoperative period electrophysiological and clinical findings following carpal tunnel syndrome: is EMG necessary?
In this study, we aimed to compare the clinical findings and ENMG results of the patients who underwent surgery due to CTS, in the preoperative and early postoperative period. 33 wrists of 29 patients who underwent open carpal tunnel surgery in our clinic due to CTS, between 2009 and 2011, were evaluated. Electrophysiological progress was evaluated with ENMG and clinical state with Boston scale. A significant decrease was observed in the postoperative BS symptomatic (SSS) and functional (FSS) scores of patients as compared to preoperative period (P=0.00), In the electrophysiological findings, statistically significant improvement was observed in all groups but very severe CTS group (P<0.05). When preoperative and postoperative EMG findings were compared, changes in DSL and DSA values were statistically significant (P<0.05). However, no statistically significant difference was seen between DML (P=0.085) and DMA (P=246) values on the 3rd month. When an examination was conducted on the patients whose DML and DSL values could not be obtained in the preoperative EMG, DML values were obtained in the early postoperative period in 6 of 7 cases (85.71% P<0.001), and DSL values were obtained in 17 of 24 cases (70.8% P<0.000). Sensory nerve findings were more significant, showed faster recovery compared to motor nerve findings, and accompanied the clinical recovery. Performance of an EMG test, especially on sensory nerves, will be more effective in patients selected in the early period, with the exception of patients with very severe CTS.


Graphene, electrospun membranes and granular activated carbon for eliminating heavy metals, pesticides and bacteria in water and wastewater treatment processes.
Access to safe water has a significant impact on all parts of society, its growth and sustainability, both politically and socioeconomically. Consequently, the preservation of water and wastewater treatment have become a global challenge. A major contributor to water pollution is improperly or untreated industrial emissions; water resources can be contaminated with harmful pollutants, toxins or pathogenic microorganisms. Carbon's unique chemistry and its evolution due to recent advances in carbon-based technologies such as nanomaterials, offer significant potential for a variety of water purification strategies. This work details the application of carbon materials in combination with nanotechnology in the form of graphene, graphene composites, electrospun membranes and improved activated carbon in a myriad of water treatment systems with an emphasis on the removal of heavy metals, pesticides and harmful bacteria.


Lack of effects on heart rate and blood pressure in ketamine-anesthetized rats briefly exposed to ultra-wideband electromagnetic pulses.
Fourteen Sprague-Dawley rats were exposed to pulses produced by a Bournlea ultra-wideband (UWB) pulse generator (rise time, 318-337 ps; maximum E field, 19-21 kV/m). Exposures at a repetition frequency of 1 kHz for 0.5 s or to repetitive pulse trains (2-s exposure periods alternating with 2 s of no exposure, for a total of 2 min) resulted in no significant changes in heart rate or mean arterial blood pressure. These results suggest that acute whole-body exposure to UWB pulses does not have a detrimental effect on the cardiovascular system.


A Flexible Domain-Domain Hinge Promotes an Induced-fit Dominant Mechanism for the Loading of Guide-DNA into Argonaute Protein in Thermus thermophilus.
Argonaute proteins (Ago) are core components of the RNA Induced Silencing Complex (RISC) that load and utilize small guide nucleic acids to silence mRNAs or cleave foreign DNAs. Despite the essential role of Ago in gene regulation and defense against virus, the molecular mechanism of guide-strand loading into Ago remains unclear. We explore such a mechanism in the bacterium Thermus thermophilus Ago (TtAgo), via a computational approach combining molecular dynamics, bias-exchange metadynamics, and protein-DNA docking. We show that apo TtAgo adopts multiple closed states that are unable to accommodate guide-DNA. Conformations able to accommodate the guide are beyond the reach of thermal fluctuations from the closed states. These results suggest an induced-fit dominant mechanism for guide-strand loading in TtAgo, drastically different from the two-step mechanism for human Ago 2 (hAgo2) identified in our previous study. Such a difference between TtAgo and hAgo2 is found to mainly originate from the distinct rigidity of their L1-PAZ hinge. Further comparison among known Ago structures from various species indicates that the L1-PAZ hinge may be flexible in general for prokaryotic Ago's but rigid for eukaryotic Ago's.


TAF4, a subunit of transcription factor II D, directs promoter occupancy of nuclear receptor HNF4A during post-natal hepatocyte differentiation.
The functions of the TAF subunits of mammalian TFIID in physiological processes remain poorly characterised. In this study, we describe a novel function of TAFs in directing genomic occupancy of a transcriptional activator. Using liver-specific inactivation in mice, we show that the TAF4 subunit of TFIID is required for post-natal hepatocyte maturation. TAF4 promotes pre-initiation complex (PIC) formation at post-natal expressed liver function genes and down-regulates a subset of embryonic expressed genes by increased RNA polymerase II pausing. The TAF4-TAF12 heterodimer interacts directly with HNF4A and in vivo TAF4 is necessary to maintain HNF4A-directed embryonic gene expression at post-natal stages and promotes HNF4A occupancy of functional cis-regulatory elements adjacent to the transcription start sites of post-natal expressed genes. Stable HNF4A occupancy of these regulatory elements requires TAF4-dependent PIC formation highlighting that these are mutually dependent events. Local promoter-proximal HNF4A-TFIID interactions therefore act as instructive signals for post-natal hepatocyte differentiation.


Dynamic SPET parameters of 123I-MIBG cardiac imaging.
Early dynamic and late 123I-MIBG SPET studies were performed to investigate several parameters used to distinguish the characteristics of various cardiac disorders. Forty-six individuals (34 non-diabetic, 12 diabetic) with or without heart disease were included in the study. Early dynamic and late static SPET images were acquired using a triple-headed gamma camera. After selecting mid-sections from vertical (VLA) and horizontal (HLA) long-axis images, regions of interest were created over the apex, whole heart and anterior, inferior, septal and lateral walls of the heart. Various uptake ratios at 3, 11 and 19 min and 4 h after injection (HU3, HU11, HU19, DUP) and clearances (Kse: between HU3 and HU11; Ke: between HU11 and HU19; Kd: between HU19 and DUP) were calculated. There were significant differences among various cardiac pathologies on the delayed images. Cardiomyopathy patients showed the lowest uptake on the delayed images. When all segments in normal patients and all involved segments in myocardial infarcted patients were compared, there was significantly lower uptake of MIBG in infarcted segments at all time points. Kd showed the lowest value compared with Kse and Ke. In cardiomyopathy patients, Kse, Ke and Kd were significantly different from each other. Both Kse and Ke were significantly higher in cardiomyopathy patients than in normal patients. In conclusion, the results of this study are in line with published data and precise measurement of uptake and clearance was possible when excluding background and blood pool activity.


Health insurance coverage and mortality revisited.
To improve understanding of the relationship between lack of insurance and risk of subsequent mortality. Adults who reported being uninsured or privately insured in the National Health Interview Survey from 1986 to 2000 were followed prospectively for mortality from initial interview through 2002. Baseline information was obtained on 672,526 respondents, age 18-64 at the time of the interview. Follow-up information on vital status was obtained for 643,001 (96 percent) of these respondents, with approximately 5.4 million person-years of follow-up. Relationships between insurance status and subsequent mortality are examined using Cox proportional hazard survival analysis. Adjusted for demographic, health status, and health behavior characteristics, the risk of subsequent mortality is no different for uninsured respondents than for those covered by employer-sponsored group insurance at baseline (hazard ratio 1.03, 95 percent confidence interval [CI], 0.95-1.12). Omitting health status as a control variable increases the estimated hazard ratio to 1.10 (95 percent CI, 1.03-1.19). Also omitting smoking status and body mass index increases the hazard ratio to 1.20 (95 percent CI, 1.15-1.24). The estimated association between lack of insurance and mortality is not larger among disadvantaged subgroups; when the analysis is restricted to amenable causes of death; when the follow-up period is shortened (to increase the likelihood of comparing the continuously insured and continuously uninsured); and does not change after people turn 65 and gain Medicare coverage. The Institute of Medicine's estimate that lack of insurance leads to 18,000 excess deaths each year is almost certainly incorrect. It is not possible to draw firm causal inferences from the results of observational analyses, but there is little evidence to suggest that extending insurance coverage to all adults would have a large effect on the number of deaths in the United States.


Fibrinogen Concentrate in the Special Operations Forces Environment.
Hemorrhage is the most common cause of death among Special Operations Force (SOF) soldiers. Bringing remote damage control resuscitation into the far-forward combat environment is logistically challenging, as it requires blood products that generally require a robust cold chain. Alternatively, lyophilized products such as fibrinogen concentrate, which does not require thawing or blood group compatibility testing before use, might be advantageous in damage control resuscitation in the battlefield. In this report, we review the evidence for the use of fibrinogen concentrate in the Canadian SOF environment. The literature on the use of fibrinogen concentrate in the trauma setting was reviewed by Canadian Forces Services Working Group, in three separate meetings. Multiple stakeholders were consulted to obtain authoritative perspectives from subject matter experts on the use of fibrinogen concentrate in the Canadian SOF environment. We also conducted a comparison review of fibrinogen content, pathogen risk, shelf life, and methods required for use for fresh frozen plasma, cryoprecipitate, and fibrinogen concentrate relevant to their application in the far-forward combat environment. Indications and a protocol for the use of fibrinogen as an adjunct to fresh whole blood were formulated based on a literature review and clinical expert opinion. Alternative strategies and other lyophilized blood products were considered before selecting fibrinogen concentrate as the lyophilized blood product of choice. Fibrinogen concentrate is an ABO-universal blood product with an excellent safety profile. Training was conducted by subject matter experts within civilian trauma centers and at military training facilities. The clinical efficacy and safety were confirmed by monitoring the use of fibrinogen concentrate in deployed combat settings. Fibrinogen concentrate is a useful adjunct to remote damage control resuscitation in the SOF environment. Fibrinogen concentrate was found to be robust for transport into the SOF environment and is widely accepted among SOF operators and medics.


New perspectives of tissue remodelling with neural stem and progenitor cell-based therapies.
Compelling evidence exists that neural stem cell-based therapies protect the central nervous system (CNS) from chronic inflammatory degeneration, such as that occurring in experimental autoimmune encephalomyelitis and stroke. It was first assumed that stem cells directly replace lost cells but it is now becoming clearer that they might be able to protect the nervous system through mechanisms other than cell replacement. In immune-mediated experimental demyelination and stroke, transplanted neural stem/precursor cells (NPCs) are able to mediate efficient bystander myelin repair and axonal rescue. This is dependent on multiple capacities that transplanted NPCs exhibit within specific microenvironments after transplantation. However, a comprehensive understanding of the mechanisms by which NPCs exert their therapeutic impact is lacking. Here we will review some of the most recent evidence--and discuss some of the likely mechanisms--that support the remarkable capacity of NPCs to cross-talk with endogenous cells and to remodel the injured nervous system when applied as novel therapeutic regimes. We foresee that the exploitation of the innate mechanisms regulating these modalities of cell-to-cell communication has realistic chances of revolutionizing most of the actual understanding of stem cell biology and its application to regenerative medicine and CNS repair.


GMP-compliant radiosynthesis of [18F]altanserin and human plasma metabolite studies.
[(18)F]altanserin is the preferred radiotracer for in-vivo labeling of serotonin 2A receptors by positron emission tomography (PET). We report a modified synthesis procedure suited for reliable production of multi-GBq amounts of [(18)F]altanserin useful for application in humans. We introduced thermal heating for drying of [(18)F]fluoride as well as for the reaction instead of microwave heating. We furthermore describe solid phase extraction and HPLC procedures for quantitative determination of [(18)F]altanserin and metabolites in plasma. The time course of arterial plasma activity with and without metabolite correction was determined. 90 min after bolus injection, 38.4% of total plasma activity derived from unchanged [(18)F]altanserin. Statistical comparison of kinetic profiles of [(18)F]altanserin metabolism in plasma samples collected in the course of two ongoing studies employing placebo, the serotonin releaser dexfenfluramine and the hallucinogen psilocybin, revealed the same tracer metabolism. We conclude that metabolite analysis for correction of individual plasma input functions used in tracer modeling is not necessary for [(18)F]altanserin studies involving psilocybin or dexfenfluramine treatment.


Staphylococcal and other bacterial species associated with intramammary infections in Danish dairy herds.
Four thousand six hundred forty-five quarter milk samples from 1179 cows from 20 commercial dairy herds were examined in order to determine the prevalence of bacterial species. A total of 859 isolates from 839 (18.1%) culture positive samples could be assigned to 34 different species and subspecies. Diagnostics of staphylococcal species was based on conventional procedures able to differentiate between all 36 species and subspecies presently acknowledged. Staphylococcus aureus was found in 10.2% of the samples and was the most common species isolated. Streptococcus dysgalactiae (1.6%) and Streptococcus uberis (1.4%) were the second and third most common species isolated. Seventeen different coagulase negative staphylococcal species (CNS) were found in 4.1% of the samples. The most frequently isolated CNS were S. epidermidis (1.3%), S. chromogenes (1.0%) and S. simulans (0.7%). Isolates of S. aureus were phage typed, and isolates of S. epidermidis were investigated by phage typing, antibiogram typing, and biotyping. A total of 378 (79.9%) isolates of S. aureus could be typed by phages, assigning them to 18 different phage types. However, 6 phage types accounted for 92.1% of the typable isolates. One to 2 phage types predominated within each herd. Eleven (18%) isolates of S. epidermidis could be typed by phages, assigning the isolates to 3 different types. Biotyping of S. epidermidis produced a total of 8 different types, the most common accounting for 29.5% of the isolates. A total of 6 different antibiogram types were observed among all isolates of S. epidermidis. Resistance towards penicillin (36.1%), tetracycline (9.8%) and streptomycin (9.8%), were recorded in the isolates of S. epidermidis. However, 35 (57.4%) of the isolates were susceptible to all 12 antibiotics tested.


Behavioural response of a migratory songbird to geographic variation in song and morphology.
Sexually selected traits contribute substantially to evolutionary diversification, for example by promoting assortative mating. The contributing traits and their relevance for reproductive isolation differ between species. In birds, sexually selected acoustic and visual signals often undergo geographic divergence. Clines in these phenotypes may be used by both sexes in the context of sexual selection and territoriality. The ways conspecifics respond to geographic variation in phenotypes can give insights to possible behavioural barriers, but these may depend on migratory behaviour. We studied a migratory songbird, the Stonechat, and tested its responsiveness to geographic variation in male song and morphology. The traits are acquired differently, with possible implications for population divergence. Song can evolve quickly through cultural transmission, and thus may contribute more to the establishment of geographic variation than inherited morphological traits. We first quantified the diversity of song traits from different populations. We then tested the responses of free-living Stonechats of both sexes to male phenotype with playbacks and decoys, representing local and foreign stimuli derived from a range of distances from the local population. Both sexes discriminated consistently between stimuli from different populations, responding more strongly to acoustic and morphological traits of local than foreign stimuli. Time to approach increased, and time spent close to the stimuli and number of tail flips decreased consistently with geographic distance of the stimulus from the local population. Discriminatory response behaviour was more consistent for acoustic than for morphological traits. Song traits of the local population differed significantly from those of other populations. Evaluating an individual's perception of geographic variation in sexually selected traits is a crucial first step for understanding reproductive isolation mechanisms. We have demonstrated that in both sexes of Stonechats the responsiveness to acoustic and visual signals decreased with increasing geographic distance of stimulus origin. These findings confirm consistent, fine discrimination for both learned song and inherited morphological traits in these migratory birds. Maintenance or further divergence in phenotypic traits could lead to assortative mating, reproductive isolation, and potentially speciation.


Rho GTPases control ciliary epithelium cells proliferation and progenitor profile induction in vivo.
Rho GTPases play a central role in actin-based cytoskeleton reorganization and regulate multiple signaling pathways that control gene transcription, cell survival, and proliferation. We investigated the effect of Rho GTPases on cell cycle regulation and progenitor genes expression on mouse ciliary epithelium (CE), a potential source of progenitor/stem cells in the adult retina. Rho GTPases were activated by intraocular injection of lysophosphatidic acid and inactivated by Clostridium difficile Toxin A (general Rho GTPase inhibitor), NSC23766 (Rac1 activation inhibitor), or Y27632 (Rho-associated protein kinase [ROCK] inhibitor). Thereafter, we assayed for RhoA, RhoB, and Rac1 protein localization in CE cells. Proliferation was examined by the expression levels of cell cycle regulators p27(kip), p16(INK4a), and Ki67 and the effects on progenitors by determining the changes in Pax6 and Chx10 progenitor markers expression. All GTPases investigated were expressed in mouse CE cells. Activation increased the coexpression of Pax6 and Chx10, but had no significant effect on the proliferation of CE cells. In contrast, Rho GTPases inactivation increased cell proliferation and potentiated the proliferative effect of growth factors. Specific inactivation of Rac1 or ROCK increased the levels of Ki67 and decreased the expression of the cell cycle inhibitors p27(kip) and p16(INK4a). This study reports that Rho GTPase modulation (activation and inactivation) controls the expression of retinal progenitor genes and proliferation, respectively, in the adult ciliary epithelial progenitor/stem cells of rodent eyes. The modulation of these two different mechanisms (proliferation and reprogramming) may provide a potential new approach in retinal repair.


Plant traits moderate pollen limitation of introduced and native plants: a phylogenetic meta-analysis of global scale.
The role of pollination in the success of invasive plants needs to be understood because invasives have substantial effects on species interactions and ecosystem functions. Previous research has shown both that reproduction of invasive plants is often pollen limited and that invasive plants can have high seed production, motivating the questions: How do invasive populations maintain reproductive success in spite of pollen limitation? What species traits moderate pollen limitation for invaders? We conducted a phylogenetic meta-analysis with 68 invasive, 50 introduced noninvasive and 1931 native plant populations, across 1249 species. We found that invasive populations with generalist pollination or pollinator dependence were less pollen limited than natives, but invasives and introduced noninvasives did not differ. Invasive species produced 3× fewer ovules/flower and >250× more flowers per plant, compared with their native relatives. While these traits were negatively correlated, consistent with a tradeoff, this did not differ with invasion status. Invasive plants that produce many flowers and have floral generalisation are able to compensate for or avoid pollen limitation, potentially helping to explain the invaders' reproductive successes.


Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination.
Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with beta-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and beta-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination.


Interactions of Freshwater Cyanobacteria with Bacterial Antagonists.
Cyanobacterial and algal mass development, or blooms, have severe effects on freshwater and marine systems around the world. Many of these phototrophs produce a variety of potent toxins, contribute to oxygen depletion, and affect water quality in several ways. Coexisting antagonists, such as cyanolytic bacteria, hold the potential to suppress, or even terminate, such blooms, yet the nature of this interaction is not well studied. We isolated 31 cyanolytic bacteria affiliated with the genera Pseudomonas, Stenotrophomonas, Acinetobacter, and Delftia from three eutrophic freshwater lakes in Sweden and selected four phylogenetically diverse bacterial strains with strong-to-moderate lytic activity. To characterize their functional responses to the presence of cyanobacteria, we performed RNA sequencing (RNA-Seq) experiments on coculture incubations, with an initial predator-prey ratio of 1:1. Genes involved in central cellular pathways, stress-related heat or cold shock proteins, and antitoxin genes were highly expressed in both heterotrophs and cyanobacteria. Heterotrophs in coculture expressed genes involved in cell motility, signal transduction, and putative lytic activity. l,d-Transpeptidase was the only significantly upregulated lytic gene in Stenotrophomonas rhizophila EK20. Heterotrophs also shifted their central metabolism from the tricarboxylic acid cycle to the glyoxylate shunt. Concurrently, cyanobacteria clearly show contrasting antagonistic interactions with the four tested heterotrophic strains, which is also reflected in the physical attachment to their cells. In conclusion, antagonistic interactions with cyanobacteria were initiated within 24 h, and expression profiles suggest varied responses for the different cyanobacteria and studied cyanolytes.IMPORTANCE Here, we present how gene expression profiles can be used to reveal interactions between bloom-forming freshwater cyanobacteria and antagonistic heterotrophic bacteria. Species-specific responses in both heterotrophs and cyanobacteria were identified. The study contributes to a better understanding of the interspecies cellular interactions underpinning the persistence and collapse of cyanobacterial blooms.


Improved axial position detection in optical tweezers measurements.
We investigate the axial position detection of a trapped microsphere in an optical trap by using a quadrant photodiode. By replacing the photodiode with a CCD camera, we obtain detailed information on the light scattered by the microsphere. The correlation of the interference pattern with the axial position displays complex behavior with regions of positive and negative interference. By analyzing the scattered light intensity as a function of the axial position of the trapped sphere, we propose a simple method to increase the sensitivity and control the linear range of axial position detection.


A case of renal artery thrombosis with renal infarction.
Renal artery thrombosis is a rare, but serious and often misdiagnosed, condition. Emergency physicians and other physicians need to consider this diagnosis in unexplained flank pain, especially in patients with risk factors for this disease. In this case report, the authors review a case of renal infarction caused by renal artery thrombosis in a patient with risk factors for thrombosis but no previous history of thromboembolism. A review of scholarly articles was performed and the case is discussed in the context of the current knowledge of this condition. Common presenting symptoms, features of the history and risk factors will all be discussed herein. Diagnostic evaluation of flank pain in the setting of the suspicion of renal infarction will be discussed, including the modalities of high-resolution computed tomography, renal angiography, scintography and ultrasound. Acute management and prognosis will also be discussed.


Vascular toxicity associated with anti-angiogenic drugs.
Over the past two decades, the treatment of cancer has been revolutionised by the highly successful introduction of novel molecular targeted therapies and immunotherapies, including small-molecule kinase inhibitors and monoclonal antibodies that target angiogenesis by inhibiting vascular endothelial growth factor (VEGF) signaling pathways. Despite their anti-angiogenic and anti-cancer benefits, the use of VEGF inhibitors (VEGFi) and other tyrosine kinase inhibitors (TKIs) has been hampered by potent vascular toxicities especially hypertension and thromboembolism. Molecular processes underlying VEGFi-induced vascular toxicities still remain unclear but inhibition of endothelial NO synthase (eNOS), reduced nitric oxide (NO) production, oxidative stress, activation of the endothelin system, and rarefaction have been implicated. However, the pathophysiological mechanisms still remain elusive and there is an urgent need to better understand exactly how anti-angiogenic drugs cause hypertension and other cardiovascular diseases (CVDs). This is especially important because VEGFi are increasingly being used in combination with other anti-cancer dugs, such as immunotherapies (immune checkpoint inhibitors (ICIs)), other TKIs, drugs that inhibit epigenetic processes (histone deacetylase (HDAC) inhibitor) and poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, which may themselves induce cardiovascular injury. Here, we discuss vascular toxicities associated with TKIs, especially VEGFi, and provide an up-to-date overview on molecular mechanisms underlying VEGFi-induced vascular toxicity and cardiovascular sequelae. We also review the vascular effects of VEGFi when used in combination with other modern anti-cancer drugs.


Structural texture similarity metrics for image analysis and retrieval.
We develop new metrics for texture similarity that accounts for human visual perception and the stochastic nature of textures. The metrics rely entirely on local image statistics and allow substantial point-by-point deviations between textures that according to human judgment are essentially identical. The proposed metrics extend the ideas of structural similarity and are guided by research in texture analysis-synthesis. They are implemented using a steerable filter decomposition and incorporate a concise set of subband statistics, computed globally or in sliding windows. We conduct systematic tests to investigate metric performance in the context of "known-item search," the retrieval of textures that are "identical" to the query texture. This eliminates the need for cumbersome subjective tests, thus enabling comparisons with human performance on a large database. Our experimental results indicate that the proposed metrics outperform peak signal-to-noise ratio (PSNR), structural similarity metric (SSIM) and its variations, as well as state-of-the-art texture classification metrics, using standard statistical measures.


Oestrogen enforces the integrity of blood vessels in the bone during pregnancy and menopause.
The mammalian skeletal system shows sex differences in structure, functions, ageing and disease incidences. The role of blood vessels in physiological, regenerative and pathological bone functions indicates the requisite to understanding their sex specificity. Here, we find oestrogen regulates blood vessel physiology during pregnancy and menopause through oestrogen receptor alpha (ERα) and G-protein coupled oestrogen receptor-1 (Gper1) but not ERβ-dependent signalling in mice. Oestrogen regulates BECs' lipid use and promotes lipolysis of adipocytes and FA uptake from the microenvironment. Low oestrogen conditions skew endothelial FA metabolism to accumulate lipid peroxides (LPO), leading to vascular ageing. High ferrous ion levels in female BECs intensify LPO accumulation and accelerate the ageing process. Importantly, inhibiting LPO generation using liproxstatin-1 in aged mice significantly improved bone heath. Thus, our findings illustrate oestrogen's effects on BECs and suggest LPO targeting could be an efficient strategy to manage blood and bone health in females.


Usefulness of hounsfield unit and density in the assessment and treatment of urinary stones.
Computed tomography (CT) is widely used to examine stones in the urinary system. In addition to the size and location of the stone and the overall health of the kidney, CT can also assess the density of the stone in Hounsfield units (HU). The HU, or Hounsfield density, measured by CT, is related to the density of the tissue or stone. A number of studies have assessed the use of HU in urology. HUs have been used to predict the type and opacity of stones during diagnosis, and the efficacy has been assessed using methods including extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), ureterorenoscopic ureterolithotripsy (URSL), and medical expulsive treatment (MET). Previous studies have focused on the success rate of HU for predicting the type of stone and of ESWL treatment. Understanding the composition of the stone plays a key role in determining the most appropriate treatment modality. The most recent reports have suggested that the HU value and its variants facilitate prediction of stone composition. However, the inclusion of data regarding urine, such as pH and presence of crystals, increases the predictive accuracy. HUs, which now form part of the clinical guidelines, allow us to predict the success of ESWL; therefore, they should be taken into account when ESWL is considered as a treatment option. However, there are currently insufficient data available regarding the value of HU for assessing the efficacy of PCNL, URSL, and MET. Studies performed to date suggest that these values would make a significant contribution to the diagnosis and treatment of urinary system stones. However, more data are required to assess this further.


p73 and p63: why do we still need them?
When p73 and p63 were initially described as homologues of the tumor suppressor p53, the three family members seemed almost exchangeable, raising the question why all three were retained during evolution. It later turned out that the corresponding genes, TP63 and TP73, appear phylogenetically older than TP53, and that their targeted deletion causes severe developmental defects, in contrast to a deletion of TP53. Hence, p63 and p73 are responsible for biological effects that cannot be elicited by p53 alone. Here, we provide an overview of properties ascribed to p63 and p73 that distinguish them from p53. Differences occur at the following levels: (i) protein structure, especially with regard to the aminoterminal transactivation domains and the carboxyterminal portions unique to p63 and p73; (ii) regulation, affecting mRNA levels, posttranslational modifications and interaction with other cellular proteins; (iii) activities, resulting in the regulation of gene expression, the programming of development, and the emergence of tumors. We speculate that, during the course of evolution, p63 and p73 have first pursued a broader range of activities, whereas p53 later specialized on genome maintenance.


Heterogeneity of planarian stem cells in the S/G2/M phase.
The planarian adult stem cell (pASC) population has a specific molecular signature and can be easily visualized and isolated by flow cytometry. However, the lack of antibodies against specific surface markers for planarian cells prevents a deeper analysis of specific cell populations. Here, if we describe the results of the immunoscreening of pASC plasma membrane proteins (PMPs). A novel papain-based method for planarian cell dissociation enabling both high yield and improved cell viability was used to generate single cell preparations for PMP purification. PMPs were used for intraperitoneal immunization of mice and thus about 1000 hybridoma clones were generated and screened. Supernatants collected from the hybridoma clones were first screened by ELISA and then by live immuno-staining. About half of these supernatants stained all the planarian cells, whereas the other half specifically labeled a subfraction thereof. A detailed analysis of two hybridoma supernatants revealed that large subfractions of the X1, X2 and Xin populations differentially express specific membrane markers. Quantitative PCR data disclosed a correlation between the immunostaining results and the expression of markers of the early and late progeny, also for those pASCs in the S/G2/M phase of the cell cycle (X1 population). Thus, about two thirds of the cycling pASCs showed a specific membrane signature coupled with the expression of markers hitherto considered to be restricted to differentiating, post-mitotic progeny. In summary, a library of 66 monoclonal antibodies against planarian PMPs was generated. The analysis of two of the clones generated revealed that a subset of cells of the X1 population expresses early and late progeny markers, which might indicate that these cells are committed while still proliferating. The findings demonstrate the usefulness of our PMP antibody library for planarian research.


HMMCONVERTER 1.0: a toolbox for hidden Markov models.
Hidden Markov models (HMMs) and their variants are widely used in Bioinformatics applications that analyze and compare biological sequences. Designing a novel application requires the insight of a human expert to define the model's architecture. The implementation of prediction algorithms and algorithms to train the model's parameters, however, can be a time-consuming and error-prone task. We here present HMMConverter, a software package for setting up probabilistic HMMs, pair-HMMs as well as generalized HMMs and pair-HMMs. The user defines the model itself and the algorithms to be used via an XML file which is then directly translated into efficient C++ code. The software package provides linear-memory prediction algorithms, such as the Hirschberg algorithm, banding and the integration of prior probabilities and is the first to present computationally efficient linear-memory algorithms for automatic parameter training. Users of HMMConverter can thus set up complex applications with a minimum of effort and also perform parameter training and data analyses for large data sets.


Expansion of RiPP biosynthetic space through integration of pan-genomics and machine learning uncovers a novel class of lanthipeptides.
Microbial natural products constitute a wide variety of chemical compounds, many which can have antibiotic, antiviral, or anticancer properties that make them interesting for clinical purposes. Natural product classes include polyketides (PKs), nonribosomal peptides (NRPs), and ribosomally synthesized and post-translationally modified peptides (RiPPs). While variants of biosynthetic gene clusters (BGCs) for known classes of natural products are easy to identify in genome sequences, BGCs for new compound classes escape attention. In particular, evidence is accumulating that for RiPPs, subclasses known thus far may only represent the tip of an iceberg. Here, we present decRiPPter (Data-driven Exploratory Class-independent RiPP TrackER), a RiPP genome mining algorithm aimed at the discovery of novel RiPP classes. DecRiPPter combines a Support Vector Machine (SVM) that identifies candidate RiPP precursors with pan-genomic analyses to identify which of these are encoded within operon-like structures that are part of the accessory genome of a genus. Subsequently, it prioritizes such regions based on the presence of new enzymology and based on patterns of gene cluster and precursor peptide conservation across species. We then applied decRiPPter to mine 1,295 Streptomyces genomes, which led to the identification of 42 new candidate RiPP families that could not be found by existing programs. One of these was studied further and elucidated as a representative of a novel subfamily of lanthipeptides, which we designate class V. The 2D structure of the new RiPP, which we name pristinin A3 (1), was solved using nuclear magnetic resonance (NMR), tandem mass spectrometry (MS/MS) data, and chemical labeling. Two previously unidentified modifying enzymes are proposed to create the hallmark lanthionine bridges. Taken together, our work highlights how novel natural product families can be discovered by methods going beyond sequence similarity searches to integrate multiple pathway discovery criteria.


First molecular data on the phylum Loricifera: an investigation into the phylogeny of ecdysozoa with emphasis on the positions of Loricifera and Priapulida.
Recent progress in molecular techniques has generated a wealth of information for phylogenetic analysis. Among metazoans all but a single phylum have been incorporated into some sort of molecular analysis. However, the minute and rare species of the phylum Loricifera have remained elusive to molecular systematists. Here we report the first molecular sequence data (nearly complete 18S rRNA) for a member of the phylum Loricifera, Pliciloricus sp. from Korea. The new sequence data were analyzed together with 52 other ecdysozoan sequences, with all other phyla represented by three or more sequences. The data set was analyzed using parsimony as an optimality criterion under direct optimization as well as using a Bayesian approach. The parsimony analysis was also accompanied by a sensitivity analysis. The results of both analyses are largely congruent, finding monophyly of each ecdysozoan phylum, except for Priapulida, in which the coelomate Meiopriapulus is separate from a clade of pseudocoelomate priapulids. The data also suggest a relationship of the pseudocoelomate priapulids to kinorhynchs, and a relationship of nematodes to tardigrades. The Bayesian analysis placed the arthropods as the sister group to a clade that includes tardigrades and nematodes. However, these results were shown to be parameter dependent in the sensitivity analysis. The position of Loricifera was extremely unstable to parameter variation, and support for a relationship of loriciferans to any particular ecdysozoan phylum was not found in the data.


Inflated applicants: attribution errors in performance evaluation by professionals.
When explaining others' behaviors, achievements, and failures, it is common for people to attribute too much influence to disposition and too little influence to structural and situational factors. We examine whether this tendency leads even experienced professionals to make systematic mistakes in their selection decisions, favoring alumni from academic institutions with high grade distributions and employees from forgiving business environments. We find that candidates benefiting from favorable situations are more likely to be admitted and promoted than their equivalently skilled peers. The results suggest that decision-makers take high nominal performance as evidence of high ability and do not discount it by the ease with which it was achieved. These results clarify our understanding of the correspondence bias using evidence from both archival studies and experiments with experienced professionals. We discuss implications for both admissions and personnel selection practices.


Effect of scapular function training on chronic pain in the neck/shoulder region: a randomized controlled trial.
Neck and shoulder complaints are common among employees in occupations characterized by intensive computer use. Treatment has varied from passive rest to active treatments and active treatments have often been divided into either training of the painful area or the surrounding musculature avoiding direct training of the painful area. Our study investigates the effect of the latter approach. The purpose of this study was in a randomised controlled trial to investigate if intensive scapular function training (SFT)-in terms of training of the lower trapezius and the serratus anterior muscle while minimizing direct training of the upper trapezius-is effective in reducing pain in adults with chronic non-specific pain in the neck/shoulder region. 47 office workers with chronic non-specific pain in the neck/shoulder region were randomized to 10 weeks 3 × 20 min SFT with training supervision or to a control group. At baseline and at follow-up the participants were tested for maximum isometric shoulder strength by a blinded tester. Further, once a week participants reported pain intensity of the neck/shoulder during the previous week. In intention-to-treat analysis neck- and shoulder pain decreased 2.0 (95 % CI 0.35; 3.64) in SFT compared with control group (p < 0.05). Pressure Pain Threshold (PPT) increased 129 kPa in the lower trapezius in SFT compared with the control group (p < 0.01). Shoulder elevation strength increased 7.7 kg in SFT compared with the control group (p < 0.01) with no change in shoulder protraction strength. SFT reduces pain intensity and increases shoulder elevation strength in adults with chronic non-specific pain in the neck/shoulder region. The magnitude of improvement in pain intensity was clinically relevant.


The Development of the General Factor of Psychopathology 'p Factor' Through Childhood and Adolescence.
Recent studies have suggested that the structure of psychopathology may be usefully represented in terms of a general factor of psychopathology (p-factor) capturing variance common to a broad range of symptoms transcending diagnostic domains in addition to specific factors capturing variance common to smaller subsets of more closely related symptoms. Little is known about how the general co-morbidity captured by this p-factor develops and whether general co-morbidity increases or decreases over childhood and adolescence. We evaluated two competing hypotheses: 1) dynamic mutualism which predicts growth in general co-morbidity and associated p-factor strength over time and 2) p-differentiation which predicts that manifestations of liabilities towards psychopathology become increasingly specific over time. Data came from the Zurich Project on the Social Development of Children and Youths (z-proso), a longitudinal study of a normative sample (approx. 50 % male) measured at 8 time points from ages 7 to 15. We operationalised general co-morbidity as p-factor strength in a bi-factor model and used omega hierarchical to track how this changed over development. In contrast to the predictions of both dynamic mutualism and p-differentiation, p-factor strength remained relatively constant over the studied period suggesting that such processes do not govern the interplay between psychopathological symptoms during this phase of development. Future research should focus on earlier phases of development and on factors that maintain the consistency of symptom-general covariation across this period.


Deciphering the differential response of two human fibroblast cell lines following Chikungunya virus infection.
Chikungunya virus (CHIKV) is an arthritogenic member of the Alphavirus genus (family Togaviridae) transmitted by Aedes mosquitoes. CHIKV is now known to target non hematopoietic cells such as epithelial, endothelial cells, fibroblasts and to less extent monocytes/macrophages. The type I interferon (IFN) response is an early innate immune mechanism that protects cells against viral infection. Cells express different pattern recognition receptors (including TLR7 and RIG-I) to sense viruses and to induce production of type I IFNs which in turn will bind to their receptor. This should result in the phosphorylation and translocation of STAT molecules into the nucleus to promote the transcription of IFN-stimulated antiviral genes (ISGs). We herein tested the capacity of CHIKV clinical isolate to infect two different human fibroblast cell lines HS 633T and HT-1080 and we analyzed the resulting type I IFN innate immune response. Indirect immunofluorescence and quantitative RT-PCR were used to test for the susceptibility of both fibroblast cell lines to CHIKV. Interestingly, the two fibroblast cell lines HS 633T and HT-1080 were differently susceptible to CHIKV infection and the former producing at least 30-fold higher viral load at 48 h post-infection (PI). We found that the expression of antiviral genes (RIG-I, IFN-β, ISG54 and ISG56) was more robust in the more susceptible cell line HS 633T at 48 h PI. Moreover, CHIKV was shown to similarly interfere with the nuclear translocation of pSTAT1 in both cell lines. Critically, CHIKV can control the IFN response by preventing the nuclear translocation of pSTAT1 in both fibroblast cell lines. Counter-intuitively, the relative resistance of HT-1080 cells to CHIKV infection could not be attributed to more robust innate IFN- and ISG-dependent antiviral responses. These cell lines may prove to be valuable models to screen for novel mechanisms mobilized differentially by fibroblasts to control CHIKV infection, replication and spreading from cell to cell.


I becomes we, but where is me? The unity-division paradox when caring for a relative with dementia: A qualitative study.
The number of older people living with dementia is increasing. Admiral Nurses work with these individuals and their families in the UK to manage challenges associated with the condition, providing guidance, advice and reassurance, alongside practical solutions. To explore the input of Admiral Nurses as part of people's journey to becoming and being a carer for someone with dementia. A qualitative study was conducted to describe and understand how Admiral Nurses are experienced and encountered by carers as part of their narrative around supporting a relative with dementia. Semi-structured interviews were conducted with 19 carers between November 2017-April 2018. They lasted between 45 and 90 min. Thematic analysis was used to interpret data. An overarching concept of "the unity-division paradox" was derived from the data. This highlights the complex interchange between the carer with (a) the person with dementia, (b) other individuals and (c) external services. Such interactions can make carers feel part of a larger network (unity) but also as if they are on their own, fighting on behalf of the person with dementia (division). This concept was underpinned by the following themes: (a) I becomes we; (b) My private world is encroached by dementia; (c) I'm left navigating an unwieldy system; (d) Are you with or against us?; and (e) Recreating boundaries to rediscover me. The identity and unique characteristics and interests of those caring for a person with dementia may be lost as they encounter tensions associated with the unity-division paradox. Admiral Nurses can help carers feel less alone in managing internal and external struggles by supporting them to do their best for a loved one with dementia. Understanding carers' experience and supporting their work may help to increase and sustain their capacity to provide care.


Linking electronic health records to better understand breast cancer patient pathways within and between two health systems.
In a fragmented health care system, research can be challenging when one seeks to follow cancer patients as they seek care which can continue for months or years and may reflect many physician and patient decisions. Claims data track patients, but lack clinical detail. Linking routine electronic health record (EHR) data with clinical registry data allows one to gain a more complete picture of the patient journey through a cancer care episode. However, valid analytical approaches to examining care trajectories must be longitudinal and account for the dynamic nature of what is "seen" in the EHR. The Oncoshare database combines clinical detail from the California Cancer Registry and EHR data from two large health care organizations in the same catchment area-a multisite community practice and an academic medical center-for all women treated in either organization for breast cancer from 2000 to 2012. We classified EHR encounters data according to typical periods of the cancer care episode (screening, diagnosis, treatment) and posttreatment surveillance, as well as by facility used to better characterize patterns of care for patients seen at both organizations. We identified a "treated" cohort consisting of women receiving interventions for their initial cancer diagnosis, and classified their encounters over time across multiple dimensions (type of care, provider of care, and timing of care with respect to their cancer diagnosis). Forty-three percent of the patients were treated at the academic center only, 42 percent at the community center only, and 16 percent of the patients obtained care at both health care organizations. Compared to women seen at only one organization, the last group had similar-length initial care episodes, but more frequently had multiple episodes and longer observation periods. Linking EHR data from neighboring systems can enhance our information on care trajectories, but careful consideration of the complexity of the treatment process and data generating mechanisms is necessary to make valid inferences. If analyzed as a timeline, and with careful characterization of diagnostic tests, surgical interventions, and type and frequency of physician encounters, the pathways taken by women through their breast cancer episode may lead to better understanding of patient decisions.


Unexplained symptoms after terrorism and war: an expert consensus statement.
Twelve years of concern regarding a possible "Gulf War syndrome" has now given way to societal concerns of a "World Trade Center syndrome" and efforts to prevent unexplained symptoms following the most recent war in Iraq. These events serve to remind us that unexplained symptoms frequently occur after war and are likely after terrorist attacks. An important social priority is to recognize, define, prevent, and care for individuals with unexplained symptoms after war and related events (eg, terrorism, natural or industrial disasters). An international, multidisciplinary, and multiinstitutional consensus project was completed to summarize current knowledge on unexplained symptoms after terrorism and war.


Raman spectroscopy and the material study of nanocomposite membranes from poly(ε-caprolactone) with biocompatibility testing in osteoblast-like cells.
Modern medical treatment can be improved by nanotechnology methods for preparing nanocomposites with novel physical, chemical and biological properties. The materials studied and analysed as membranes were produced from poly(ε-caprolactone) (PCL), which contained identical amounts of nano-additives, either montmorillonite (MMT) or functionalized multi-walled carbon nanotubes (MWCNT-f), while the reference membranes were obtained from unmodified PCL. In addition to the conventional methods used in the study of materials for medical purposes such as DSC, contact angle measurements, surface topography, Raman spectroscopy was also applied. Raman microspectroscopy can decode the phenomenon that occurs in the polymer in contact with the nanoparticles. Besides identifying the vibrations of certain functional groups, the calculation of crystallinity parameters is also possible, by which the most intense interactions within the nanocomposites can be analysed. The Raman studies indicate that each of the nano-additives reacts differently with the polymer matrix, which results in material properties that influence its biological properties. MWCNT-f interacts preferentially with the oxygen-containing groups, and particularly with the backbone regions in the vicinity of the single CO bond. The human osteoblast-like MG-63 cells, cultured on the PCL/MWCNT-f membrane for three days, show almost 100% viability.


Genetic changes in primary and recurrent prostate cancer by comparative genomic hybridization.
Genetic changes leading to the development of prostate cancer and factors that underlie the clinical progression of the disease are poorly characterized. Here, we used comparative genomic hybridization (CGH) to screen for DNA sequence copy number changes along all chromosomes in 31 primary and 9 recurrent uncultured prostate carcinomas. The aim of the study was to identify those chromosome regions that contain genes important for the development of prostate cancer and to identify genetic markers of tumor progression. CGH analysis indicated that 74% of primary prostate carcinoma showed DNA sequence copy number changes. Losses were 5 times more common than gains and most often involved 8p (32%), 13q (32%), 6q (22%), 16q (19%), 18q (19%), and 9p (16%). Allelic loss studies with 5 polymorphic microsatellite markers for 4 different chromosomes were done from 13 samples and showed a 76% concordance with CGH results. In local recurrences that developed during endocrine therapy, there were significantly more gains (P < 0.001) and losses (P < 0.05) of DNA sequences than in primary tumors, with gains of 8q (found in 89% of recurrences versus 6% of primary tumors), X (56% versus 0%), and 7 (56% versus 10%), as well as loss of 8p (78% versus 32%), being particularly often involved. In conclusion, our CGH results indicate that losses of several chromosomal regions are common genetic changes in primary tumors, suggesting that deletional inactivation of putative tumor suppressor genes in these chromosomal sites is likely to underlie development of prostate cancer. Furthermore, the pattern of genetic changes seen in recurrent tumors with the frequent gains of 7, 8q, and X suggests that the progression of prostate cancer and development of hormone-independent growth may have a distinct genetic basis. These chromosome aberrations may have diagnostic utility as markers of prostate cancer progression.


Pest population dynamics are related to a continental overwintering gradient.
Overwintering success is an important determinant of arthropod populations that must be considered as climate change continues to influence the spatiotemporal population dynamics of agricultural pests. Using a long-term monitoring database and biologically relevant overwintering zones, we modeled the annual and seasonal population dynamics of a common pest, Helicoverpa zea (Boddie), based on three overwintering suitability zones throughout North America using four decades of soil temperatures: the southern range (able to persist through winter), transitional zone (uncertain overwintering survivorship), and northern limits (unable to survive winter). Our model indicates H. zea population dynamics are hierarchically structured with continental-level effects that are partitioned into three geographic zones. Seasonal populations were initially detected in the southern range, where they experienced multiple large population peaks. All three zones experienced a final peak between late July (southern range) and mid-August to mid-September (transitional zone and northern limits). The southern range expanded by 3% since 1981 and is projected to increase by twofold by 2099 but the areas of other zones are expected to decrease in the future. These changes suggest larger populations may persist at higher latitudes in the future due to reduced low-temperature lethal events during winter. Because H. zea is a highly migratory pest, predicting when populations accumulate in one region can inform synchronous or lagged population development in other regions. We show the value of combining long-term datasets, remotely sensed data, and laboratory findings to inform forecasting of insect pests.


Testing moderation in network meta-analysis with individual participant data.
Meta-analytic methods for combining data from multiple intervention trials are commonly used to estimate the effectiveness of an intervention. They can also be extended to study comparative effectiveness, testing which of several alternative interventions is expected to have the strongest effect. This often requires network meta-analysis (NMA), which combines trials involving direct comparison of two interventions within the same trial and indirect comparisons across trials. In this paper, we extend existing network methods for main effects to examining moderator effects, allowing for tests of whether intervention effects vary for different populations or when employed in different contexts. In addition, we study how the use of individual participant data may increase the sensitivity of NMA for detecting moderator effects, as compared with aggregate data NMA that employs study-level effect sizes in a meta-regression framework. A new NMA diagram is proposed. We also develop a generalized multilevel model for NMA that takes into account within-trial and between-trial heterogeneity and can include participant-level covariates. Within this framework, we present definitions of homogeneity and consistency across trials. A simulation study based on this model is used to assess effects on power to detect both main and moderator effects. Results show that power to detect moderation is substantially greater when applied to individual participant data as compared with study-level effects. We illustrate the use of this method by applying it to data from a classroom-based randomized study that involved two sub-trials, each comparing interventions that were contrasted with separate control groups. Copyright © 2016 John Wiley & Sons, Ltd.


Epigenetic Aging: More Than Just a Clock When It Comes to Cancer.
The incidence of cancer, adjusted for secular trends, is directly related to age, and advanced chronologic age is one of the most significant risk factors for cancer. Organismal aging is associated with changes at the molecular, cellular, and tissue levels and is affected by both genetic and environmental factors. The specific mechanisms through which these age-associated molecular changes contribute to the increased risk of aging-related disease, such as cancer, are incompletely understood. DNA methylation, a prominent epigenetic mark, also changes over a lifetime as part of an "epigenetic aging" process. Here, we give an update and review of epigenetic aging, in particular, the phenomena of epigenetic drift and epigenetic clock, with regard to its implication in cancer etiology. We discuss the discovery of the DNA methylation-based biomarkers for biological tissue age and the construction of various epigenetic age estimators for human clinical outcomes and health/life span. Recent studies in various types of cancer point to the significance of epigenetic aging in tumorigenesis and its potential use for cancer risk prediction. Future studies are needed to assess the potential clinical impact of strategies focused on lowering cancer risk by preventing premature aging or promoting healthy aging.


Osteoblast, fibroblast and in vivo biological response to poly(vinylidene fluoride) based composite materials.
Electroactive materials can be taken to advantage for the development of sensors and actuators as well as for novel tissue engineering strategies. Composites based on poly(vinylidene fluoride), PVDF, have been evaluated with respect to their biological response. Cell viability and proliferation were performed in vitro both with Mesenchymal Stem Cells differentiated to osteoblasts and Human Fibroblast Foreskin 1. In vivo tests were also performed using 6-week-old C57Bl/6 mice. It was concluded that zeolite and clay composites are biocompatible materials promoting cell response and not showing in vivo pro-inflammatory effects which renders both of them attractive for biological applications and tissue engineering, opening interesting perspectives to development of scaffolds from these composites. Ferrite and silver nanoparticle composites decrease osteoblast cell viability and carbon nanotubes decrease fibroblast viability. Further, carbon nanotube composites result in a significant increase in local vascularization accompanied an increase of inflammatory markers after implantation.


Guided asthma self-management or patient self-adjustment? Using patients' narratives to better understand adherence to asthma treatment.
The purpose of this study was to better understand patients' perspective of asthma self-management by focusing on the sociocultural and medical context shaping patients' illness representations and individual decisions. We conducted a secondary analysis of semi-structured interviews carried out as part of a multicentered collective qualitative case study. In total, 24 patients, aged 2-76 years with a confirmed diagnosis of asthma (or were parents of a child), who renewed the prescription for inhaled corticosteroids in the past year, participated in this study. The thematic analysis focused on asthma-related events and experiences reported by the patients. Consistent with narrative inquiry, similar patterns were grouped together, and three vignettes representing the different realities experienced by the patients were created. The comparison of experiences and events reported by the patients suggested that patients' perceptions and beliefs regarding asthma and treatment goals influenced their self-management-related behaviors. More specifically, the medical context in which the patients were followed (ie, frame in which the medical encounter takes place, medical recommendations provided) contributed to shape their understanding of the disease and the associated treatment goals. In turn, a patient's perception of the disease and the treatment goals influenced asthma self-management behaviors related to environmental control, lifestyle habits, and medication intake. Current medical recommendations regarding asthma self-management highlight the importance of the physicians' guidance through the provision of a detailed written action plan and asthma education. These data suggest that while physicians contribute to shaping patients' beliefs and perceptions about the disease and treatment goals, patients tend to listen to their own experience and manage the disease accordingly. Thus, a medical encounter between the patient and the physician, aiming at enhancing a meaningful conversation about the disease, may lead the patient to approach the disease in a more effective manner, which goes beyond taking preventative paths to avoid symptoms.


Vitamin levels in a selected population in the Czech Republic.
The work objective was to monitor nutritional habits in the observed group of professional soldiers with the focus on eating food with the content of antioxidant carriers. Then to show present state of health and nutrition in the group on the basis of anthropometric measurements and biochemical examinations and finally to observe the level of antioxidant vitamins in the observed group of professional soldiers. The group included 171 healthy individuals, 152 men and 19 women. Their average age was 34.2±7.9 years. The venous blood was taken for biochemical examinations in all individuals on a fast. Anthropometric measurements (weight, height, caliperation, waist circumferences), blood pressure and pulse were taken continually in all individuals. Simple questionnaires were administered to all participants for the complete evaluation of present health and for the registration of eating habits of the observed persons. The study results show that retinol and a-tocoferol levels in the observed group were within a normal range. The average concentration of vitamin C in this group was 54 mmol/l and reached nearly the values given in other European countries. But concentrations of β-caroten and lycopen in serum were up to 50% lower in comparison with concentrations in population in the countries of West Europe. Higher vitamin C and β caroten serum levels were found in individuals who respond in a questionnaire they eat fruit and vegetables or supplements of vitamin preparations every day. Statistically lower levels of vitamin C, β karoten and lycopen in the group of obese people (compared with the group of normal weight people) show decreased level of antioxidant protection of the organism and the risk of cardiovascular diseases. The results show that it is necessary to ensure optimal food not only with an energetic diet value but also with a proper input of antioxidant carriers in the form of fresh vegetables and fruit every day.


Ultrafast transient absorption revisited: Phase-flips, spectral fingers, and other dynamical features.
We rebuild the theory of ultrafast transient-absorption/transmission spectroscopy starting from the optical response of an individual molecule to incident femtosecond pump and probe pulses. The resulting description makes use of pulse propagators and free molecular evolution operators to arrive at compact expressions for the several contributions to a transient-absorption signal. In this alternative description, which is physically equivalent to the conventional response-function formalism, these signal contributions are conveniently expressed as quantum mechanical overlaps between nuclear wave packets that have undergone different sequences of pulse-driven optical transitions and time-evolution on different electronic potential-energy surfaces. Using this setup in application to a simple, multimode model of the light-harvesting chromophores of PC577, we develop wave-packet pictures of certain generic features of ultrafast transient-absorption signals related to the probed-frequency dependence of vibrational quantum beats. These include a Stokes-shifting node at the time-evolving peak emission frequency, antiphasing between vibrational oscillations on opposite sides (i.e., to the red or blue) of this node, and spectral fingering due to vibrational overtones and combinations. Our calculations make a vibrationally abrupt approximation for the incident pump and probe pulses, but properly account for temporal pulse overlap and signal turn-on, rather than neglecting pulse overlap or assuming delta-function excitations, as are sometimes done.


A cognitive behavioural theory of anorexia nervosa.
A cognitive behavioural theory of the maintenance of anorexia nervosa is proposed. It is argued that an extreme need to control eating is the central feature of the disorder, and that in Western societies a tendency to judge self-worth in terms of shape and weight is superimposed on this need for self-control. The theory represents a synthesis and extension of existing accounts. It is 'new', not so much because of its content, but because of its exclusive focus on maintenance, its organisational structure and its level of specification. It is suggested that the theory has important implications for treatment.


Genomic Microbial Epidemiology Is Needed to Comprehend the Global Problem of Antibiotic Resistance and to Improve Pathogen Diagnosis.
Contamination of waste effluent from hospitals and intensive food animal production with antimicrobial residues is an immense global problem. Antimicrobial residues exert selection pressures that influence the acquisition of antimicrobial resistance and virulence genes in diverse microbial populations. Despite these concerns there is only a limited understanding of how antimicrobial residues contribute to the global problem of antimicrobial resistance. Furthermore, rapid detection of emerging bacterial pathogens and strains with resistance to more than one antibiotic class remains a challenge. A comprehensive, sequence-based genomic epidemiological surveillance model that captures essential microbial metadata is needed, both to improve surveillance for antimicrobial resistance and to monitor pathogen evolution. Escherichia coli is an important pathogen causing both intestinal [intestinal pathogenic E. coli (IPEC)] and extraintestinal [extraintestinal pathogenic E. coli (ExPEC)] disease in humans and food animals. ExPEC are the most frequently isolated Gram negative pathogen affecting human health, linked to food production practices and are often resistant to multiple antibiotics. Cattle are a known reservoir of IPEC but they are not recognized as a source of ExPEC that impact human or animal health. In contrast, poultry are a recognized source of multiple antibiotic resistant ExPEC, while swine have received comparatively less attention in this regard. Here, we review what is known about ExPEC in swine and how pig production contributes to the problem of antibiotic resistance.