High-dimensional classification methods have been a major target of machine learning for the automatic classification of patients who suffer from Alzheimer's disease (AD). One major issue of automatic classification is the feature-selection method from high-dimensional data. In this paper, a novel approach for statistical feature reduction and selection in high-dimensional magnetic resonance imaging (MRI) data based on the probability distribution function (PDF) is introduced. To develop an automatic computer-aided diagnosis (CAD) technique, this research explores the statistical patterns extracted from structural MRI (sMRI) data on four systematic levels. First, global and local differences of gray matter in patients with AD compared to healthy controls (HCs) using the voxel-based morphometric (VBM) technique with 3-Tesla 3D T1-weighted MRI are investigated. Second, feature extraction based on the voxel clusters detected by VBM on sMRI and voxel values as volume of interest (VOI) is used. Third, a novel statistical feature-selection process is employed, utilizing the PDF of the VOI to represent statistical patterns of the respective high-dimensional sMRI sample. Finally, the proposed feature-selection method for early detection of AD with support vector machine (SVM) classifiers compared to other standard feature selection methods, such as partial least squares (PLS) techniques, is assessed. The performance of the proposed technique is evaluated using 130 AD and 130 HC MRI data from the ADNI dataset with 10-fold cross validation(1). The results show that the PDF-based feature selection approach is a reliable technique that is highly competitive with respect to the state-of-the-art techniques in classifying AD from high-dimensional sMRI samples.

BACKGROUND

Human mitochondrial peptide deformylase (PDF) has been proposed as a novel cancer therapeutic target. However, very little is known about its expression and regulation in human tissues. The purpose of this study was to characterize the expression pattern of PDF in cancerous tissues and to identify mechanisms that regulate its expression.

METHODS

The mRNA expression levels of PDF and methionine aminopeptidase 1D (MAP1D), an enzyme involved in a related pathway with PDF, were determined using tissue panels containing cDNA from patients with various types of cancer (breast, colon, kidney, liver, lung, ovarian, prostate, or thyroid) and human cell lines. Protein levels of PDF were also determined in 2 colon cancer patients via western blotting. Colon cancer cells were treated with inhibitors of ERK, Akt, and mTOR signaling pathways and the resulting effects on PDF and MAP1D mRNA levels were determined by qPCR for colon and lung cancer cell lines. Finally, the effects of a PDF inhibitor, actinonin, on the proliferation of breast, colon, and prostate cell lines were determined using the CyQUANT assay.

RESULTS

PDF and MAP1D mRNA levels were elevated in cancer cell lines compared to non-cancer lines. PDF mRNA levels were significantly increased in breast, colon, and lung cancer samples while MAP1D mRNA levels were increased in just colon cancers. The expression of PDF and MAP1D varied with stage in these cancers. Further, PDF protein expression was elevated in colon cancer tissue samples. Inhibition of the MEK/ERK, but not PI3K or mTOR, pathway reduced the expression of PDF and MAP1D in both colon and lung cancer cell lines. Further, inhibition of PDF with actinonin resulted in greater reduction of breast, colon, and prostate cancer cell proliferation than non-cancer cell lines.

CONCLUSIONS

This is the first report showing that PDF is over-expressed in breast, colon, and lung cancers, and the first evidence that the MEK/ERK pathway plays a role in regulating the expression of PDF and MAP1D. The over-expression of PDF in several cancers and the inhibition of cancer cell growth by a PDF inhibitor suggest this enzyme may act as an oncogene to promote cancer cell proliferation.

The small ventral lateral neurons (sLNvs) constitute a central circadian pacemaker in the Drosophila brain. They organize daily locomotor activity, partly through the release of the neuropeptide pigment-dispersing factor (PDF), coordinating the action of the remaining clusters required for network synchronization. Despite extensive efforts, the basic principles underlying communication among circadian clusters remain obscure. We identified classical neurotransmitters released by sLNvs through disruption of specific transporters. Adult-specific RNAi-mediated downregulation of the glycine transporter or impairment of glycine synthesis in LNv neurons increased period length by nearly an hour without affecting rhythmicity of locomotor activity. Electrophysiological recordings showed that glycine reduces spiking frequency in circadian neurons. Interestingly, downregulation of glycine receptor subunits in specific sLNv targets impaired rhythmicity, revealing involvement of glycine in information processing within the network. These data identify glycinergic inhibition of specific targets as a cue that contributes to the synchronization of the circadian network.

Peptide deformylase (PDF) is an attractive target for antibacterial drug discovery. Progress in the biological characterisation of the enzyme, coupled with newly obtained mechanistic and structural insight, enabled the pharmaceutical industry to discover potent PDF inhibitors that can be considered as clinical development candidates for this new class of antibacterial agents. The in vitro and in vivo data for several lead PDF inhibitors suggest that the current PDF inhibitors are most suitable for the treatment of respiratory tract infections and they are not cross-resistant to the current clinically used antibiotics. Two PDF inhibitors, BB-83698 and VIC-104959, have progressed to Phase I clinical trials by intravenous and oral administration, respectively. Both of these compounds show promising in vitro and in vivo efficacy and an excellent safety profile. The pharmacokinetics in humans for both of the compounds suggest the possibility of a twice-daily dosing regimen for clinical use. Thus far, all of the data suggest a promising future for this new class of antibacterial agents.

The concept of insect photoperiodism based on a circadian clock has been supported by many studies demonstrating that the behavioural circadian rhythm and the photoperiodic response are driven by the same circadian clock genes. However, the neuronal mechanism of the circadian clock underlying photoperiodism is poorly understood. To examine whether circadian rhythm and photoperiodism share a neuronal mechanism, we focused on the neurons that express neuropeptide pigment-dispersing factor (PDF) in the bean bug, Riptortus pedestris. PDF has been identified as an important regulator of the insect circadian rhythm and is expressed in circadian clock neurons of various insect species. In R. pedestris, PDF immunoreactivity was detected in some clusters of cells and their fibres in the optic lobe and the protocerebrum. cDNA encoding a PDF precursor protein was highly conserved between R. pedestris and many other insects. Differences between day and night were not observed in the immunolabelling intensity in cell bodies of PDF-immunoreactive neurons and pdf mRNA expression levels in the head. Surgical removal of the region containing PDF-immunoreactive cell bodies at the medulla disrupted the photoperiodic regulation of diapause. However, gene suppression of pdf by RNA interference did not affect the photoperiodic response. These results suggest that the region containing PDF-immunoreactive somata is important for the photoperiodic response in R. pedestris, but pdf mRNA expression is probably not required for the response.

Pigment-dispersing factor (PDF) denotes a conserved family of homologous neuropeptides present in several invertebrate groups, including mollusks, nematodes, insects, and crustaceans (referred to here as pigment-dispersing hormone [PDH]). With regard to their encoding genes (pdf, pdh), insects possess only one, nematodes two, and decapod crustaceans up to three, but their phylogenetic relationship is unknown. To shed light on the origin and diversification of pdf/pdh homologs in Panarthropoda (Onychophora + Tardigrada + Arthropoda) and other molting animals (Ecdysozoa), we analyzed the transcriptomes of five distantly related onychophorans and a representative tardigrade and searched for putative pdf homologs in publically available genomes of other protostomes. This revealed only one pdf homolog in several mollusk and annelid species; two in Onychophora, Priapulida, and Nematoda; and three in Tardigrada. Phylogenetic analyses suggest that the last common ancestor of Panarthropoda possessed two pdf homologs, one of which was lost in the arthropod or arthropod/tardigrade lineage, followed by subsequent duplications of the remaining homolog in some taxa. Immunolocalization of PDF-like peptides in six onychophoran species, by using a broadly reactive antibody that recognizes PDF/PDH peptides in numerous species, revealed an elaborate system of neurons and fibers in their central and peripheral nervous systems. Large varicose projections in the heart suggest that the PDF neuropeptides functioned as both circulating hormones and locally released transmitters in the last common ancestor of Onychophora and Arthropoda. The lack of PDF-like-immunoreactive somata associated with the onychophoran optic ganglion conforms to the hypothesis that onychophoran eyes are homologous to the arthropod median ocelli.

The World Health Organisation and International Society of Hypertension (WHO/ISH) cardiovascular disease (CVD) risk assessment charts have been implemented in many low- and middle-income countries as part of the WHO Package of Essential Non-Communicable Disease (PEN) Interventions for Primary Health Care in Low-Resource settings. Evaluation of the WHO/ISH cardiovascular risk charts and their use is a key priority and since they only exist in paper or PDF formats, we developed a simple R implementation of the charts for all epidemiological subregions of the world. The main strengths of this implementation are that it is built in a free, open-source, coding language with simple syntax, can be modified by the user, and can be used with a standard computer.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement.

UNASSIGNED

The multifactorial mechanisms associated with radical reductions in HIV-1 reservoirs after allogeneic hematopoietic stem cell transplant (allo-HSCT), including a case of HIV cure, are not fully understood.

UNASSIGNED

To investigate the mechanism of HIV-1 eradication associated with allo-HSCT.

UNASSIGNED

Nested case series within the IciStem observational cohort.

UNASSIGNED

Multicenter European study.

UNASSIGNED

6 HIV-infected, antiretroviral-treated participants who survived more than 2 years after allo-HSCT with CCR5 wild-type donor cells.

UNASSIGNED

HIV DNA analysis, HIV RNA analysis, and quantitative viral outgrowth assay were performed in blood, and HIV DNA was also measured in lymph nodes, ilea, bone marrow, and cerebrospinal fluid. A humanized mouse model was used for in vivo detection of the replication-competent blood cell reservoir. HIV-specific antibodies were measured in plasma.

UNASSIGNED

Analysis of the viral reservoir showed that 5 of 6 participants had full donor chimera in T cells within the first year after transplant, undetectable proviral HIV DNA in blood and tissue, and undetectable replication-competent virus (<0.006 infectious unit per million cells). The only participant with detectable virus received cord blood stem cells with an antithymocyte globulin-containing conditioning regimen, did not develop graft-versus-host disease, and had delayed complete standard chimerism in T cells (18 months) with mixed ultrasensitive chimera. Adoptive transfer of peripheral CD4+ T cells to immunosuppressed mice resulted in no viral rebound. HIV antibody levels decreased over time, with 1 case of seroreversion.

UNASSIGNED

Few participants.

UNASSIGNED

Allo-HSCT resulted in a profound long-term reduction in the HIV reservoir. Such factors as stem cell source, conditioning, and a possible "graft-versus-HIV-reservoir" effect may have contributed. Understanding the mechanisms involved in HIV eradication after allo-HSCT can enable design of new curative strategies.

UNASSIGNED

The Foundation for AIDS Research (amfAR).

BACKGROUND

The impact of a low-glucose peritoneal dialysis (PD) regimen on biomarkers of peritoneal inflammation, fibrosis and membrane integrity remains to be investigated.

METHODS

In a randomized, prospective study, 80 incident PD patients received either a low-glucose regimen comprising Physioneal (P), Extraneal (E) and Nutrineal (N) (Baxter Healthcare Corporation, Deerfield, IL, USA) (PEN group), or Dianeal (control group) for 12 months, after which both groups continued with Dianeal dialysis for 6 months. Serum and dialysate levels of vascular endothelial growth factor (VEGF), decorin, hepatocyte growth factor (HGF), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), hyaluronan (HA), adiponectin, soluble-intracellular adhesion molecule (s-ICAM), vascular cell adhesion molecule-1 (VCAM-1) and P-selectin, and dialysate cancer antigen 125 (CA125), were measured after 12 and 18 months. This paper focuses on results after 12 months, when patients in the PEN group changed to glucose-based PD fluid (PDF).

RESULTS

At the end of 12 months, effluent dialysate levels of CA125, decorin, HGF, IL-6, adiponectin and adhesion molecules were significantly higher in the PEN group compared to controls, but all decreased after patients switched to glucose-based PDF. Macrophage migration inhibitory factor level was lower in the PEN group but increased after changing to glucose-based PDF and was similar to controls at 18 months. Serum adiponectin level was higher in the PEN group at 12 months, but was similar in the 2 groups at 18 months. Body weight, residual renal function, ultrafiltration volume and total Kt/V did not differ between both groups. Dialysate-to-plasma creatinine ratio at 4 h was higher in the PEN group at 12 months and remained so after switching to glucose-based PDF.

CONCLUSIONS

Changes in the biomarkers suggest that the PEN PD regimen may be associated with better preservation of peritoneal membrane integrity and reduced systemic vascular endothelial injury.

This paper focuses on the study of the effect of the change of the crystal size on the shape and width of the X-ray diffraction patterns for defatted and deproteinized bones as well as incinerated biogenic hydroxyapatite obtained from bovine, porcine, and human bones. Inductively Couple Plasma showed the presence of some ions such as Mg, K, Al, Fe, Zn, and Na for all samples. The nanometric size of the crystals was determined through High Resolution Transmission Electron Microscopy in which ordered crystals were found. The calcination of raw clean bones at 720 °C produced a transition of crystal size from nano to micro due to a coalescence phenomenon, this was accompanied by a decrease of the peak width of the X-ray diffraction patterns due to the decrease of the inelastic scattering contribution from the microcrystals. A simulation of the effect of the crystallite size on the shape and width of the X-ray patterns was done using PDF-4 software which confirmed that raw ordered bone crystals produce broad peaks which so far have been erroneously assigned to polycrystalline hydroxyapatite with low crystalline quality.

OBJECTIVE

Gallbladder perforation is a rare but life threatening complication of acute cholecystitis. Aim of this study is to present our clinical experience with gallbladder perforation.

METHODS

Thirty-seven of retrospectively reviewed 1042 acute cholecystitis patients were found to have gallbladder (GB) perforation. Perforations due to trauma, iatrogenic causes, and gallbladder carcinoma were excluded.

RESULTS

Abdominal ultrasound (US) showed gall stones in all of the patients with type-I and type-II gallbladder perforations (GBP), extensive intraperitoneal free fluid in 9 patients with type-I GBP, and a small amount of pericholecystic free fluid in 7 patients with type-II GBP. Abdominal US did not show GB wall defect in any of the patients, but showed intraperitoneal free gall stone in one type-I and one type-II GBP patients. CT revealed GB wall thickening in all of the patients, gall stones in 7 patients, extensive intraperitoneal free fluid in 7 patients, a small amount of pericholecystic free fluid in 8 patients, and GB perforation sites in 4 patients. Abdominal CT and US detected subhepatic abscesses in 3 patients.

CONCLUSIONS

Early diagnosis of gallbladder perforation and immediate surgical intervention are of crucial importance. Unfortunately, the limited success of US and CT for detecting the GBP let us advocate early and urgent surgery (Tab. 3, Ref. 13). Full Text (Free, PDF) www.bmj.sk.

Intradermal immunization is gaining increased attention due to multiple factors: (1) intradermal (ID) vaccination has been shown to induce improved immunogenicity compared to intramuscular (IM) vaccination; (2) ID vaccination has been shown to have a dose-sparing potential over IM leading to a reduced vaccine cost and an increased availability of vaccines worldwide. However, the currently used Mantoux technique for ID injection is difficult to standardize and requires training. The aim of the study was (1) to assess the epidermal and dermal thickness at the proximal ventral and dorsal forearm (PVF & PDF) and deltoid in adults aged 18-65years (2) to determine the maximum penetration depth and needle characteristics for the development of a platform of medical devices suited for intradermal injection, VAX-ID™.

Mean thickness of the PVF, PDF and deltoid were measured using high-frequency ultrasound of healthy adults aged 18-65years. Correlation with gender, age and BMI was assessed using Mann-Whitney U Test, Spearman correlation and Wilcoxon Signed Ranks Test, respectively.

Results showed an overall mean skin thickness of 1.19mm (0.65-1.55mm) at the PVF, 1.44mm (0.78-1.84mm) at the PDF, and 2.12mm (1,16-3.19mm) at the deltoid. Thickness of PVF & PDF and deltoid were significantly different for men vs women (pmean<0.001, <0.001, <0.001, and pmin<0.001, 0.012, <0.001, respectively). A significant association was found for age at the deltoid region (p<0.001). Skin thickness for PVF, PDF & deltoid was significantly associated to BMI (p<0.001).

Significant differences in skin thickness were seen for the PVF, PDF and deltoid region for gender, and BMI. Age only influenced the skin thickness at deltoid region. A needle length of 1.0mm is best option for intradermal injection at the dorsal forearm (NCT02363465).

BACKGROUND

Randomized, prospective trials involving multi-institutional collaboration have become a central part of clinical and translational research. However, data management and coordination of multi-center studies is a complex process that involves developing systems for data collection and quality control, tracking data queries and resolutions, as well as developing communication procedures. We describe DADOS-Prospective, an open-source Web-based application for collecting and managing prospective data on human subjects for clinical and translational trials. DADOS-Prospective not only permits users to create new clinical research forms (CRF) and supports electronic signatures, but also offers the advantage of containing, in a single environment, raw research data in downloadable spreadsheet format, source documentation and regulatory files stored in PDF format, and audit trails.

RESULTS

Feedback from formal and field usability tests was used to guide the design and development of DADOS-Prospective. To date, DADOS-Prospective has been implemented in five prospective clinical studies at our institution. Four of these studies are still in the CRF creation phase and one study has been entirely launched.

CONCLUSIONS

DADOS-Prospective has significant advantages over existing Web-based data collecting programs. At our institution, it has been demonstrated to be an efficient tool for prospective clinical studies.

Dysregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the pathogenesis of many cancers. However, the role of EZH2 in peritoneal fibrosis remains unknown. We investigated EZH2 expression in peritoneal dialysis (PD) patients and assessed its role in peritoneal fibrosis in cultured human peritoneal mesothelial cells (HPMCs) and murine models of peritoneal fibrosis induced by chlorhexidine gluconate (CG) or high glucose peritoneal dialysis fluid (PDF) by using 3-deazaneplanocin A (3-DZNeP), and EZH2 conditional knockout mice. An abundance of EZH2 was detected in the peritoneum of patients with PD associated peritonitis and the dialysis effluent of long-term PD patients, which was positively correlated with expression of transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor, and interleukin-6. EZH2 was found highly expressed in the peritoneum of mice following injury by CG or PDF. In both mouse models, treatment with 3-DZNeP attenuated peritoneal fibrosis and inhibited activation of several pro-fibrotic signaling pathways, including TGF-β1/Smad3, Notch1, epidermal growth factor receptor and Src. EZH2 inhibition also inhibited STAT3 and nuclear factor-κB phosphorylation, and reduced lymphocyte and macrophage infiltration and angiogenesis in the injured peritoneum. 3-DZNeP effectively improved high glucose PDF-associated peritoneal dysfunction by decreasing the dialysate-to-plasma (D/P) ratio of BUN and increasing the ratio of dialysate glucose at 2 h after PDF injection to initial dialysate glucose. Moreover, delayed administration of 3-DZNeP inhibited peritoneal fibrosis progression, reversed established peritoneal fibrosis and reduced expression of tissue inhibitor of metalloproteinase 2 (TIMP2), and matrix metalloproteinase-2 and -9. Finally, EZH2-KO mice exhibited less peritoneal fibrosis than EZH2-WT mice. In HPMCs, treatment with EZH2 siRNA or 3-DZNeP suppressed TGF-β1-induced upregulation of α-SMA and Collagen I and preserved E-cadherin. These results indicate that EZH2 is a key epigenetic regulator that promotes peritoneal fibrosis. Targeting EZH2 may have the potential to prevent and treat peritoneal fibrosis. This article is protected by copyright. All rights reserved.

The behavior of seismicity in the area candidate to suffer a main shock is investigated after the observation of the Seismic Electric Signal activity until the impending main shock. This is based on the view that the occurrence of earthquakes is a critical phenomenon to which statistical dynamics may be applied. In the present work, analysing the time series of small earthquakes, the concept of natural time chi was used and the results revealed that the approach to criticality itself can be manifested by the probability density function (<em>PDF</em>) of kappa(1) calculated over an appropriate statistical ensemble. Here, kappa(1) is the variance kappa(1)(=<chi(2>>-<chi>(2)) resulting from the power spectrum of a function defined as Phi(omega)= summation operator(k=1)(N) p(k) exp(iomegachi(k)), where p(k) is the normalized energy of the k-th small earthquake and omega the natural frequency. This <em>PDF</em> exhibits a maximum at kappa(1) asymptotically equal to 0.070 a few days before the main shock. Examples are presented, referring to the magnitude 6 approximately 7 class earthquakes that occurred in Greece.

Nematodes and arthropods are the most speciose animal groups and possess Class 2 B1 G-protein coupled receptors (GPCRs). Existing models of invertebrate Class 2 B1 GPCR evolution are mainly centered on Caenorhabditis elegans and Drosophila melanogaster and a few other nematode and arthropod representatives. The present study reevaluates the evolution of metazoan Class 2 B1 GPCRs and orthologues by exploring the receptors in several nematode and arthropod genomes and comparing them to the human receptors. Three novel receptor phylogenetic clusters were identified and designated cluster A, cluster B and PDF-R-related cluster. Clusters A and B were identified in several nematode and arthropod genomes but were absent from D. melanogaster and Culicidae genomes, whereas the majority of the members of the PDF-R-related cluster were from nematodes. Cluster A receptors were nematode and arthropod-specific but shared a conserved gene environment with human receptor loci. Cluster B members were orthologous to human GCGR, PTHR and Secretin members with which they probably shared a common origin. PDF-R and PDF-R related clusters were present in representatives of both nematodes and arthropods. The results of comparative analysis of GPCR evolution and diversity in protostomes confirm previous notions that C. elegans and D. melanogaster genomes are not good representatives of nematode and arthropod phyla. We hypothesize that at least four ancestral Class 2 B1 genes emerged early in the metazoan radiation, which after the protostome-deuterostome split underwent distinct selective pressures that resulted in duplication and deletion events that originated the current Class 2 B1 GPCRs in nematode and arthropod genomes.

OBJECTIVE

Type 2 diabetes disproportionately affects African American women, a population exposed to high levels of stress, including financial strain (Centers for Disease Control & Prevention, 2011, http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf). We tested a mediational model in which chronic financial strain among African American women contributes to elevated serum inflammation markers, which, in turn, lead to increased haemoglobin A1C (HbA1c) levels and risk for type 2 diabetes.

METHODS

We assessed level of financial strain four times over a 10-year period and tested its effect on two serum inflammation markers, C-reactive protein (CRP) and soluble interleukin-6 receptor (sIL-6R) in year 11 of the study. We tested the inflammation markers as mediators in the association between chronic financial strain and HbA1c, an index of average blood glucose level over several months.

METHODS

Data were from 312 non-diabetic African American women from the Family and Community Health Study (FACHS; Cutrona et al., 2000, J. Pers. Soc. Psychol., 79, 1088).

RESULTS

Chronic financial strain predicted circulating sIL-6R after controlling for age, BMI, health behaviours, and physical health measures. In turn, sIL-6R significantly predicted HbA1c levels. The path between chronic financial strain and HbA1c was significantly mediated by sIL-6R. Contrary to prediction, CRP was not predicted by chronic financial strain.

CONCLUSIONS

Results support the role of inflammatory factors in mediating the effects of psychosocial stressors on risk for type 2 diabetes. Findings have implications for interventions that boost economic security and foster effective coping as well as medical interventions that reduce serum inflammation to prevent the onset of type 2 diabetes.

An altered version of peptide deformylase from Plasmodium falciparum (PfPDF), the organism that causes the most devastating form of malaria, has been cocrystallized with a synthesized inhibitor that has submicromolar affinity for its target protein. The structure is solved at 2.2 A resolution, an improvement over the 2.8 A resolution achieved during the structural determination of unliganded PfPDF. This represents the successful outcome of modifying the protein construct in order to overcome adverse crystal contacts and other problems encountered in the study of unliganded PfPDF. Two molecules of PfPDF are found in the asymmetric unit of the current structure. The active site of each monomer of PfPDF is occupied by a proteolyzed fragment of the tripeptide-like inhibitor. Unexpectedly, each PfPDF subunit is associated with two nearly complete molecules of the inhibitor, found at a protein-protein interface. This is the first structure of a eukaryotic PDF protein, a potential drug target, in complex with a ligand.

Large bumblebee (Bombus terrestris) workers typically visit flowers to collect pollen and nectar during the day and rest in the nest at night. Small workers are less likely to forage, but instead stay in the nest and tend brood around the clock. Because Pigment Dispersing Factor (PDF) has been identified as a neuromodulator in the circadian network of insects, we used an antiserum that recognizes this peptide to compare patterns of PDF-immunoreactivity (PDF-ir) in the brains of large and small workers. Our study provides the first description of PDF distribution in the bumblebee brain, and shows a pattern that is overall similar to that of the honey bee, Apis mellifera. The brains of large bumblebee workers contained a slightly but significantly higher number of PDF-ir neurons than did the brains of small sister bees. Body size was positively correlated with area of the PDF-ir somata and negatively correlated with the maximal staining intensity. These results provide a neuronal correlate to the previously reported body size-associated variation in behavioral circadian rhythmicity. These differences in PDF-ir are consistent with the hypothesis that body size-based division of labor in bumblebees is associated with adaptations of the morphology and function of the brain circadian system.

Butyrylcholinesterase (BChE) is an enzyme expressed in multiple organs and abundant in plasma. BChE can fluctuate in course of several reasons while both hypercholiensterasemia and hypocholinesterasemia are known. Considering evidence of BChE activity alterations, hepatocellular carcinoma, chronic liver diseases and poisoning with carbamates or organophosphates can be diagnosed by activity assay. BChE is responsible for detoxification reactions, and the compounds such as cocaine, succinylcholine, and acetylsalicylic acid are degraded in the body. The detoxification can be slowed in patients carrying the K variant of the enzyme. Summarization of literature, discussion on the meaning of BChE in the body, and the principles of BChE assay in samples are described in the review (Tab. 2, Fig. 8, Ref. 86). Text in PDF www.elis.sk.

microRNAs (miRNAs) are an abundant class of small endogenous non-coding RNAs (ncRNAs) of ∼22 nucleotides (nts) in length. These small regulatory molecules are involved in diverse developmental, physiological and pathological processes. miRNAs target mRNAs (mRNAs) for translational repression and/or mRNA degradation. Predictions of miRNA binding sites facilitate experimental validation of miRNA targets. Models developed with data from CLIP studies have been used for predictions of miRNA binding sites in the whole transcriptomes of human, mouse and worm. The prediction results have been assembled into STarMirDB, a new database of miRNA binding sites available at http://sfold.wadsworth.org/starmirDB.php . STarMirDB can be searched by miRNAs or mRNAs separately or in combination. The search results are categorized into seed and seedless sites in 3' UTR, CDS and 5' UTR. For each predicted site, STarMirDB provides a comprehensive list of sequence, thermodynamic and target structural features that are known to influence miRNA: target interaction. A high resolution PDF diagram of the conformation of the miRNA:target hybrid is also available for visualization and publication. The results of a database search are available through both an interactive viewer and downloadable text files.

Renal cell carcinoma (RCC) is a heterogeneous disease made up of a number of different cancer types, with distinct histologies, clinical courses, therapeutic responses, and genetic drivers. Germline mutations in 14 genes have been associated with increased risk of RCC and can result in HIF pathway activation, chromatin dysregulation, and altered metabolism. Knowledge of these pathway alterations can inform the development of targeted therapeutic approaches. To view this SnapShot, open or download the PDF.

BACKGROUND

Vitamin K-dependent posttranslational modification of glutamate to gamma-carboxyglutamate is a biochemical feature of the vertebrate blood-clotting cascade. This conversion activates clotting factors and bone proteins, including osteocalcin, a widely accepted marker of osteoblastic activity. Vitamin K antagonists, such as warfarin, inhibit this process.

OBJECTIVE

This study was aimed at evaluating the effect of warfarin treatment on BMD and bone turnover markers and determining the relationship between BMD and bone turnover markers.

METHODS

Fifty-four warfarin users and 62 age- and sex-matched healthy controls were enrolled in 1-year prospective study. Bone mineral density, bone turnover markers, 25-hydroxyvitamin D, serum and urinary calcium measurements were done at baseline and after 12 months of warfarin treatment.

RESULTS

No differences were observed between warfarin-treated and control groups in Ca-S, Ca-dU, ALP-S, 25-OHD and BMD after 12 months.The concentrations of serum CTx (306.48 +/- 29 ng/l) and osteocalcin (16.54 +/- 1.06 ig/l) were significantly lower (p < 0.001 and p < 0.05 respectively) after 12 month in warfarin-treated group compared to control group (403.29 +/- 24.7 ng/l and 22.88 +/- 1.33 ig/l). A significant increase in serum and urinary Ca values (p < 0.05) was observed in patients with oral anticoagulant therapy after 12 month compared to baseline levels. Biochemical markers of bone metabolism did not correlate with BMD in either group.

CONCLUSIONS

The long-term use of coumarin was not associated with decreased bone mineral density in our study, but the significantly lower OC and CTx serum levels in coumarin-treated patients suggest that vitamin K has an influence on bone turnover (Tab. 3, Fig. 2, Ref. 29). Full Text in free PDF www.bmj.sk.

In a cancellation task, a participant is required to search for and cross out ("cancel") targets, which are usually embedded among distractor stimuli. The number of cancelled targets and their location can be used to diagnose the neglect syndrome after stroke. In addition, the organization of search provides a potentially useful way to measure executive control over multitarget search. Although many useful cancellation measures have been introduced, most fail to make their way into research studies and clinical practice due to the practical difficulty of acquiring such parameters from traditional pen-and-paper measures. Here we present new, open-source software that is freely available to all. It allows researchers and clinicians to flexibly administer computerized cancellation tasks using stimuli of their choice, and to directly analyze the data in a convenient manner. The automated analysis suite provides output that includes almost all of the currently existing measures, as well as several new ones introduced here. All tasks can be performed using either a computer mouse or a touchscreen as an input device, and an online version of the task runtime is available for tablet devices. A summary of the results is produced in a single A4-sized PDF document, including high quality data visualizations. For research purposes, batch analysis of large datasets is possible. In sum, CancellationTools allows users to employ a flexible, computerized cancellation task, which provides extensive benefits and ease of use.