Impact of 18F-FDG PET scan on the prevalence of benign thoracic lesions at surgical resection

OBJECTIVE: The main utility of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) lies in the staging of lung cancer. However, it can also be used to differentiate indeterminate pulmonary lesions, but its impact on the resection of benign lesions at surgery is unknown. The aim of this study was to compare the prevalence of benign lesions at thoracotomy carried out for suspected lung cancer, before and after the introduction of PET scanning in a large thoracic surgical centre. MATERIALS AND METHODS: We reviewed our prospectively recorded surgical database for all consecutive patients undergoing thoracotomy for suspected or proven lung cancer and compared the prevalence of benign lesions in 2 consecutive 2-year groups, before (group I) and after (group II) the introduction of FDG-PET scan respectively. RESULTS: Surgical resection was performed on 1233 patients during the study period. The prevalence of benign lesions at surgery in groups I and II was similar (44/626 and 41/607, both 7%), and also in group II between those who underwent FDG-PET scan and the remainder (21/301 and 20/306 respectively, both 7%). In group II, of the 21 patients with benign lesions, who underwent FDG-PET, 19 had a false positive scan (mean standardised uptake value 5.3 [range 2.6-12.7]). Of these, 13 and 4 patients respectively had non-diagnostic bronchoscopy and percutaneous transthoracic lung biopsy pre thoracotomy. There was no difference in the proportion of different benign lesions resected between group I and those with FDG-PET in group II. CONCLUSION: The introduction of FDG-PET scanning has not altered the proportion of patients undergoing thoracotomy for ultimately benign lesions, mainly due to the avidity for the isotope of some non-malignant lesions. Such false positive results need to be considered when patients with unconfirmed lung cancer are contemplated for surgical resection.

Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes.

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria.

Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.

Repeated Whole-Genome Duplication, Karyotype Reshuffling, and Biased Retention of Stress-Responding Genes in Buckler Mustard.

Whole-genome duplication (WGD) is usually followed by gene loss and karyotype repatterning. Despite evidence of new adaptive traits associated with WGD, the underpinnings and evolutionary significance of such genome fractionation remain elusive. Here, we use Buckler mustard (Biscutella laevigata) to infer processes that have driven the retention of duplicated genes after recurrent WGDs. In addition to the β- and α-WGD events shared by all Brassicaceae, cytogenetic and transcriptome analyses revealed two younger WGD events that occurred at times of environmental changes in the clade of Buckler mustard (Biscutelleae): a mesopolyploidy event from the late Miocene that was followed by considerable karyotype reshuffling and chromosome number reduction and a neopolyploidy event during the Pleistocene. Although a considerable number of the older duplicates presented signatures of retention under positive selection, the majority of retained duplicates arising from the younger mesopolyploidy WGD event matched predictions of the gene balance hypothesis and showed evidence of strong purifying selection as well as enrichment in gene categories responding to abiotic stressors. Retention of large stretches of chromosomes for both genomic copies supported the hypothesis that cycles of WGD and biased fractionation shaped the genome of this stress-tolerant polypolyloid, promoting the adaptive recruitment of stress-responding genes in the face of environmental challenges.

MetaNetX/MNXref - reconciliation of metabolites and biochemical reactions to bring together genome-scale metabolic networks.

MetaNetX is a repository of genome-scale metabolic networks (GSMNs) and biochemical pathways from a number of major resources imported into a common namespace of chemical compounds, reactions, cellular compartments-namely MNXref-and proteins. The MetaNetX.org website (http://www.metanetx.org/) provides access to these integrated data as well as a variety of tools that allow users to import their own GSMNs, map them to the MNXref reconciliation, and manipulate, compare, analyze, simulate (using flux balance analysis) and export the resulting GSMNs. MNXref and MetaNetX are regularly updated and freely available.

Ultrasound scan as a potential source of nosocomial and cross-infection: a literature review

AbstractThe authors review the main concepts regarding the importance of cleaning/disinfection of ultrasonography probes, aiming a better comprehension by practitioners and thus enabling strategies to establish a safe practice without compromising the quality of the examination and the operator productivity. In the context of biosafety, it is imperative to assume that contact with blood or body fluids represents a potential source of infection. Thus, in order to implement cleaning/disinfection practice, it is necessary to understand the principles of infection control, to consider the cost/benefit ratio of the measures to be implemented, and most importantly, to comprehend that such measures will not only benefit the health professional and the patient, but the society as a whole.

Pose-based SLAM with probabilistic scan matching algorithm using a mechanical scanned imaging sonar

This paper proposes a pose-based algorithm to solve the full SLAM problem for an autonomous underwater vehicle (AUV), navigating in an unknown and possibly unstructured environment. The technique incorporate probabilistic scan matching with range scans gathered from a mechanical scanning imaging sonar (MSIS) and the robot dead-reckoning displacements estimated from a Doppler velocity log (DVL) and a motion reference unit (MRU). The proposed method utilizes two extended Kalman filters (EKF). The first, estimates the local path travelled by the robot while grabbing the scan as well as its uncertainty and provides position estimates for correcting the distortions that the vehicle motion produces in the acoustic images. The second is an augment state EKF that estimates and keeps the registered scans poses. The raw data from the sensors are processed and fused in-line. No priory structural information or initial pose are considered. The algorithm has been tested on an AUV guided along a 600 m path within a marina environment, showing the viability of the proposed approach

Genome-wide analysis of adaptive molecular evolution in the carnivorous plant Utricularia gibba

The genome of the bladderwort Utricularia gibba provides an unparalleled opportunity to uncover the adaptive landscape of an aquatic carnivorous plant with unique phenotypic features such as absence of roots, development of water-filled suction bladders, and a highly ramified branching pattern. Despite its tiny size, the U. gibba genome accommodates approximately as many genes as other plant genomes. To examine the relationship between the compactness of its genome and gene turnover, we compared the U. gibba genome with that of four other eudicot species, defining a total of 17,324 gene families (orthogroups). These families were further classified as either 1) lineage-specific expanded/contracted or 2) stable in size. The U. gibba-expanded families are generically related to three main phenotypic features: 1) trap physiology, 2) key plant morphogenetic/developmental pathways, and 3) response to environmental stimuli, including adaptations to life in aquatic environments. Further scans for signatures of protein functional specialization permitted identification of seven candidate genes with amino acid changes putatively fixed by positive Darwinian selection in the U. gibba lineage. The Arabidopsis orthologs of these genes (AXR, UMAMIT41, IGS, TAR2, SOL1, DEG9, and DEG10) are involved in diverse plant biological functions potentially relevant for U. gibba phenotypic diversification, including 1) auxin metabolism and signal transduction, 2) flowering induction and floral meristem transition, 3) root development, and 4) peptidases. Taken together, our results suggest numerous candidate genes and gene families as interesting targets for further experimental confirmation of their functional and adaptive roles in the U. gibba's unique lifestyle and highly specialized body plan.

Prototypical Arthropod Gene Content and Genome Organisation in the Centipede Strigamia maritima

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.

Pulsatile Blood Flow Simulations in Computed Tomography(CT) Scan-Based and Idealized Geometries of Human Aorta

Blood flow in human aorta is an unsteady and complex phenomenon. The complex patterns are related to the geometrical features like curvature, bends, and branching and pulsatile nature of flow from left ventricle of heart. The aim of this work was to understand the effect of aorta geometry on the flow dynamics. To achieve this, 3D realistic and idealized models of descending aorta were reconstructed from Computed Tomography (CT) images of a female patient. The geometries were reconstructed using medical image processing code. The blood flow in aorta was assumed to be laminar and incompressible and the blood was assumed to be Newtonian fluid. A time dependent pulsatile and parabolic boundary condition was deployed at inlet. Steady and unsteady blood flow simulations were performed in real and idealized geometries of descending aorta using a Finite Volume Method (FVM) code. Analysis of Wall Shear Stress (WSS) distribution, pressure distribution, and axial velocity profiles were carried out in both geometries at steady and unsteady state conditions. The results obtained in thesis work reveal that the idealization of geometry underestimates the values of WSS especially near the region with sudden change of diameter. However, the resultant pressure and velocity in idealized geometry are close to those in real geometry

Characterization of novel genes predominantly expressed in the epididymis – from genome analyses to genetically modified mice

In mammals, post-testicular sperm maturation taking place in the epididymis is required for the spermatozoa to acquire the abilities required to fertilize the egg in vivo. The epididymal epithelial cells secrete proteins and other small molecules into the lumen, where they interact with the spermatozoa and enable necessary maturational changes. In this study different in silico, in vitro and in vivo approaches were utilized in order to find novel genes responsible for the function of the epididymis and post-testicular sperm maturation in the mouse. Available online genomic databases were analyzed to identify genes potentially expressed in the epididymis, gene expression profiling was performed by studying their expression in different mouse tissues, and significance of certain genes to fertility was assessed by generating genetically modified mouse models. A recently discovered Pate (prostate and testis expression) gene family was found to be predominantly expressed in the epididymis. It represents one of the largest known gene families expressed in the epididymis, and the members code for proteins potentially involved in defense against microorganisms. Through genetically modified mouse models CRISP4 (cysteine-rich secretory protein 4) was identified to regulate sperm acrosome reaction, and BMYC to inhibit the expression of the Myc proto-oncogene in the developing testis. A mouse line expressing iCre recombinase specifically in the epididymis was also generated. This model can be used to generate conditional, epididymis-specific knock-out models, and will be a valuable tool in fertility studies.

In silico phylogenetic and virulence gene profile analyses of avian pathogenic Escherichia coli genome sequences

Avian pathogenic Escherichia coli (APEC) infections are responsible for significant losses in the poultry industry worldwide. A zoonotic risk has been attributed to APEC strains because they present similarities to extraintestinal pathogenic E. coli (ExPEC) associated with illness in humans, mainly urinary tract infections and neonatal meningitis. Here, we present in silico analyses with pathogenic E. coli genome sequences, including recently available APEC genomes. The phylogenetic tree, based on multi-locus sequence typing (MLST) of seven housekeeping genes, revealed high diversity in the allelic composition. Nevertheless, despite this diversity, the phylogenetic tree was able to cluster the different pathotypes together. An in silico virulence gene profile was also determined for each of these strains, through the presence or absence of 83 well-known virulence genes/traits described in pathogenic E. coli strains. The MLST phylogeny and the virulence gene profiles demonstrated a certain genetic similarity between Brazilian APEC strains, APEC isolated in the United States, UPEC (uropathogenic E. coli) and diarrheagenic strains isolated from humans. This correlation corroborates and reinforces the zoonotic potential hypothesis proposed to APEC.

Microsatellite-dense genetic map: towards genome coverage in a tropical maize (Zea mays L.) population

Dense molecular genetic maps are used for an efficient quantitative trait loci (QTL) mapping and in the marker-assisted selection programs. A dense genetic map was generated with 139 microsatellite markers using 256 F2 plants generated by the crossing of two tropical maize inbred lines (L-02-03D and L-20-01F). This map presented 1,858.61 cM in length, where 10 linkage groups were found spanned, with an average interval of 13.47 cM between adjacent markers. Seventy seven percent of the maize genetic mapping bins were covered, which means an increase of 14% coverage in relation to the previous tropical maize maps. The results provide a more detailed and informative genetic map in a tropical maize population representing the first step to make possible the studies of genetic architecture to identify and map QTL and estimate their effects on the variation of quantitative traits, thus allowing the manipulation and use in tropical maize breeding programs.

Human DNA repair diseases: From genome instability to cancer

Several human genetic syndromes have long been recognized to be defective in DNA repair mechanisms. This was first discovered by Cleaver (1968), who showed that cells from patients with xeroderma pigmentosum (XP) were defective for the ability to remove ultraviolet (UV)-induced lesions from their genome. Since then, new discoveries have promoted DNA repair studies to one of the most exciting areas of molecular biology. The present work intends to give a brief summary of the main known human genetic diseases related to DNA repair and how they may be linked to acquired diseases such as cancer

Along-scan radiometric gradient in Landsat images: understanding the relation between floristic and remote sensing information in tropical forests

The along-scan radiometric gradient causes severe interpretation problems in Landsat images of tropical forests. It creates a decreasing trend in pixel values with the column number of the image. In practical applications it has been corrected assuming the trend to be linear within structurally similar forests. This has improved the relation between floristic and remote sensing information, but just in some cases. I use 3 Landsat images and 105 floristic inventories to test the assumption of linearity, and to examine how the gradient and linear corrections affect the relation between floristic and Landsat data. Results suggest the gradient to be linear in infrared bands. Also, the relation between floristic and Landsat data could be conditioned by the distribution of the sampling sites and the direction in which images are mosaicked. Additionally, there seems to be a conjunction between the radiometric gradient and a natural east-west vegetation gradient common in Western Amazonia. This conjunction might have enhanced artificially correlations between field and remotely-sensed information in previous studies. Linear corrections may remove such artificial enhancement, but along with true and relevant spectral information about floristic patterns, because they can´t separate the radiometric gradient from a natural one.