High temperature X-ray diffraction study of the oxidation products and kinetics of uranium-plutonium mixed oxides.
The oxidation products and kinetics of two sets of mixed uranium-plutonium dioxides containing 14%, 24%, 35%, 46%, 54%, and 62% plutonium treated in air were studied by means of in situ X-ray diffraction (XRD) from 300 to 1773 K every 100 K. The first set consisted of samples annealed 2 weeks before performing the experiments. The second one consisted of powdered samples that sustained self-irradiation damage. Results were compared with chosen literature data and kinetic models established for UO2. The obtained diffraction patterns were used to determine the temperature of the hexagonal M3O8 (M for metal) phase formation, which was found to increase with Pu content. The maximum observed amount of the hexagonal phase in wt % was found to decrease with Pu addition. We conclude that plutonium stabilizes the cubic phases during oxidation, but the hexagonal phase was observed even for the compositions with 62 mol % Pu. The results indicate that self-irradiation defects have a slight impact on the kinetics of oxidation and the lattice parameter even after the phase transformation. It was concluded that the lattice constant of the high oxygen phase was unaffected by the changes in the overall O/M when it was in equilibrium with small quantities of M3O8. We propose that the observed changes in the high oxygen cubic phase lattice parameter are a result of either cation migration or an increase in the miscibility of oxygen in this phase. The solubility of Pu in the hexagonal phase was estimated to be below 14 mol % even at elevated temperatures.


A primer on referring patients for psychotherapy.
Forty percent of the mental health care in this country is provided by primary care practitioners alone, and another 20% is provided by primary care practitioners working with mental health professionals. Primary care physicians can serve a valuable role by educating their patients about various forms of psychotherapy. Finding a good "fit" between patient and therapist is crucial to a good outcome. We discuss which psychotherapeutic techniques are appropriate for various emotional problems and the advantages and disadvantages of each.


Comprehensive update on current outbreak of novel coronavirus infection (2019-nCoV).
Recently, a new coronavirus disease (COVID-19) has emerged as a respiratory infection with significant concern for global public health hazards. With an initial suspicion of the animal to the human transmission for earlier cases, now the paradigm has shifted towards human to human transmission via droplets, contacts and/or through fomites. with each passing day, more and more confirmed cases are being reported worldwide which has alarmed the global authorities including World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) and the National Health Commission of the People's Republic of China to take immediate action in order to reduce the transmission and subsequent mortalities associated with COVID-19 to as minimum as possible. Unfortunately, like the previous Coronavirus outbreaks, there is no definite antiviral therapy for the treatment of confirmed cases and hence preventing ourselves from contracting 2019-nCoV is the best way to prevent it from becoming pandemic. Herein, we aim to discuss the latest updates on the origin, genomic characteristics, diagnosis, treatment options and current efforts being made by international health organizations with regards to the 2019-nCoV outbreak.


Analysis of grain boundary dynamics using event detection and cumulative averaging.
To analyze extended time series of high resolution images, we have employed automated frame-by-frame comparisons that are able to detect dynamic changes in the structure of a grain boundary in Au. Using cumulative averaging of images between events allowed high resolution measurements of the atomic relaxation in the interface with sufficient accuracy for comparison with atomistic models. Cumulative averaging was also used to observe the structural rearrangement of atomic columns at a moving step in the grain boundary. The technique of analyzing changing features in high resolution images by averaging between incidents can be used to deconvolute stochastic events that occur at random intervals and on time scales well beyond that accessible to single-shot imaging.


A case of metastatic struma ovarii treated with 131I therapy: focus on preservation of fertility and selected review of the literature.
Struma ovarii is a rare monodermal ovarian teratoma composed predominantly of mature thyroid tissue. We describe herein the case of a 22-year-old woman who underwent a right salpingo-oophorectomy for struma ovarii at the age of 12 years, who was admitted 8 years later with signs and symptoms of a left pelvic tumor. Laparoscopy detected a left ovarian endometriotic cyst and multiple nodules on the pelvic peritoneum, right lateral abdominal wall, diaphragm, vesical plica and liver. The diagnosis was abdominal and pelvic widespread dissemination of recurrent struma ovarii, with features consistent with the follicular variant of papillary thyroid carcinoma. The patient was treated with a combination of conservative surgery and two 131I administrations (cumulative activity of 350 mCi after dosimetric evaluation). Because of the high degree of hormonogenesis shown by the metastases, the first administration was performed following use of recombinant human (rh) thyroid-stimulating hormone (TSH) to reach adequate TSH levels. To avoid the 'stunning effect' and to obtain high-quality scintigraphy, a whole-body scan was performed with 123I after rh-TSH and before the 131I therapy. We also discuss the potential role and the possible benefit of using gonadotropin-releasing hormone analogs and ovarian tissue cryopreservation to preserve fertility in women treated with 131I for pelvic metastases from malignant struma ovarii.


One-particle correlation function in evanescent wave dynamic light scattering.
In order to interpret measured intensity autocorrelation functions obtained in evanescent wave scattering, their initial decay rates have been analyzed recently [P. Holmqvist, J. K. G. Dhont, and P. R. Lang, Phys. Rev. E 74, 021402 (2006); B. Cichocki, E. Wajnryb, J. Blawzdziewicz, J. K. G. Dhont, and P. R. Lang, J. Chem. Phys. 132, 074704 (2010); J. W. Swan and J. F. Brady, ibid. 135, 014701 (2011)]. A theoretical analysis of the longer time dependence of evanescent wave autocorrelation functions, beyond the initial decay, is still lacking. In this paper we present such an analysis for very dilute suspensions of spherical colloids. We present simulation results, a comparison to cumulant expansions, and experiments. An efficient simulation method is developed which takes advantage of the particular mathematical structure of the time-evolution equation of the probability density function of the position coordinate of the colloidal sphere. The computer simulation results are compared with analytic, first and second order cumulant expansions. The only available analytical result for the full time dependence of evanescent wave autocorrelation functions [K. H. Lan, N. Ostrowsky, and D. Sornette, Phys. Rev. Lett. 57, 17 (1986)], that neglects hydrodynamic interactions between the colloidal spheres and the wall, is shown to be quite inaccurate. Experimental results are presented and compared to the simulations and cumulant expansions.


The background of beta-oxidation disorders in humans. I. Theory.
Disorders in energetical processes are described from the point of view of energy production and the possibility of substitution of substrates for ATP synthesis. The effects of other diet components such as microelements (Cr3+ ions) and non-digestible oligofructans (inulin and oligofructose) as stimulatory factors on the activity of beta-oxidation and cholesterol and triacylglyceroles levels lowering are reported.


Common penile lesions.
We have briefly summarized some of the most common and confusing penile lesions likely to be seen by the urologist. We have discussed the clinical features, differential diagnosis, and treatment from the dermatologist's point of view. We have included the latest possible references, as many disorders discussed here are rapidly becoming better understood.


A second pectin lyase gene (pel2) from Aspergillus oryzae KBN616: its sequence analysis and overexpression, and characterization of the gene products.
A second pectin lyase gene, designated pel2, was isolated from a shoyu koji mold Aspergillus oryzae KBN616 and characterized. The structural gene comprised 1306 bp with three introns. The ORF encoded 375 amino acids with a signal peptide of 19 amino acids. The deduced amino acid sequence showed high similarity to those of A. oryzae Pel1, Aspergillus niger pectin lyases and Glomerella cingulata Pn1A. The pel2 gene was overexpressed under the control of the promoter of the A. oryzae TEF1 gene for purification and enzymatic characterization of its gene product. The gene product exhibited two molecular masses of 48 and 44 kDa due to different degrees of glycosylation. Both proteins had the same pH optimum of 6.0 and temperature optimum of 50 degrees C.


2H nuclear magnetic resonance spectroscopy supports larger amplitude fast motion and interference with lipid chain ordering for membrane that contains β sheet human immunodeficiency virus gp41 fusion peptide or helical hairpin influenza virus hemagglutinin fusion peptide at fusogenic pH.
Enveloped viruses are surrounded by a membrane which is obtained from an infected host cell during budding. Infection of a new cell requires joining (fusion) of the virus and cell membranes. This process is mediated by a monotopic viral fusion protein with a large ectodomain outside the virus. The ectodomains of class I enveloped viruses have a N-terminal "fusion peptide" (fp) domain that is critical for fusion and binds to the cell membrane. In this study, 2H NMR spectra are analyzed for deuterated membrane with fp from either HIV gp41 (GP) or influenza hemagglutinin (HA) fusion proteins. In addition, the HAfp samples are studied at more fusogenic pH 5 and less fusogenic pH 7. GPfp adopts intermolecular antiparallel β sheet structure whereas HAfp is a monomeric helical hairpin. The data are obtained for a set of temperatures between 35 and 0 °C using DMPC-d54 lipid with perdeuterated acyl chains. The DMPC has liquid-crystalline (Lα) phase with disordered chains at higher temperature and rippled gel (Pβ') or gel phase (Lβ') with ordered chains at lower temperature. At given temperature T, the no peptide and HAfp, pH 7 samples exhibit similar spectral lineshapes. Spectral broadening with reduced temperature correlates with the transition from Lα to Pβ' and then Lβ' phases. At given T, the lineshapes are narrower for HAfp, pH 5 vs. no peptide and HAfp, pH 7 samples, and even narrower for the GPfp sample. These data support larger-amplitude fast (>105 Hz) lipid acyl chain motion for samples with fusogenic peptides, and peptide interference with chain ordering. The NMR data of the present paper correlate with insertion of these peptides into the hydrocarbon core of the membrane and support a significant fusion contribution from the resultant lipid acyl chain disorder, perhaps because of reduced barriers between the different membrane topologies in the fusion pathway. Membrane insertion and lipid perturbation appear common to both β sheet and helical hairpin peptides.


Quantifying the Effect of Carbohydrate Mouth Rinsing on Exercise Performance.
The purpose of this study was to review the existing literature investigating carbohydrate mouth rinsing as an ergogenic aid using the effect sizes (ES) and percentage change in performance of the respective studies as outcome measures. A trivial-small average overall ES was present for the 25 studies included in the review (0.18, 95% confidence interval [CI] = 0.10-0.27). Effect sizes for the subgroups were ≥25 minutes (0.25, 95% CI = 0.14-0.36), ≤180 seconds (0.06, 95% CI = -0.03 to 0.15), resistance exercise (-0.09, 95% CI = -0.20 to 0.03) but the ES is still small. A subanalysis of ∼1-h cycling time trial performance resulted in an overall ES of 0.20 (95% CI = 0.02-0.38), and ES for performance time and power output of 0.31 (95% CI = -0.02 to 0.64) and 0.19 (95% CI = -0.09 to 0.46), respectively. Although ES were small, the average percentage change in performance in ∼1-hour trials was 2.48%, which may have implications for elite performers as this is greater than the 1.30% smallest worthwhile change recommended in the past research.


Increased Interleukin-36β Expression Promotes Angiogenesis in Japanese Atopic Dermatitis.
While atopic dermatitis (AD) is considered as a T helper 2 (Th2)-centered disease, an increase in other types of inflammatory cytokines is also noted in AD and they may also contribute to the development of the disease. Recently, the efficacy of an anti-IL-36 receptor antibody in AD was demonstrated in a clinical trial. Although there have been several reports on IL-36α and IL-36γ expression and function in AD, IL-36β has been barely studied. In this report, we examined IL-36β expression and function using clinical samples of AD and the epidermal keratinocyte cell line, HaCaT cells. We demonstrated that IL-36β expression in epidermal keratinocytes was increased in AD lesional skin compared to healthy skin. IL-36β promoted vascular endothelial growth factor A production in HaCaT keratinocytes through phosphorylation of extracellular signal-regulated kinases 1 and 2. In addition, IL-36β up-regulated placental growth factor mRNA expression in HaCaT keratinocytes. IL-36β expression levels in epidermal keratinocytes were correlated with the number of dermal vessels in AD skin. These results suggest that IL-36β may play an important role for angiogenesis in lesional skin of AD and that IL-36β can be a therapeutic target in AD.


Quantitative sensory testing of cold and vibration perception during compression of median nerve at the wrist.
We conducted a sequential study of quantitative sensory testing (QST) during compression-induced conduction block of the median nerve to determine relative vulnerability of the small and large myelinated nerve fibers. We tested cold (CPT) and vibratory perception thresholds (VPT) of the third digit in 15 healthy subjects during constant, localized compression for 30 min of the median nerve at the wrist. The orthodromic sensory nerve action potentials (SNAPs) recorded at wrist and elbow served to monitor the degree of associated conduction block. After the onset of nerve compression, it took 16 min for CPT to show the first change; VPT remained normal for 26 min. CPT recovered 2 min later than VPT after release of compression. The SNAP amplitude at the wrist diminished immediately at the start of compression and declined progressively, whereas the response at the elbow remained the same initially, showing no latency change for 20 min. A nearly identical time course of SNAP changes in the two experiments justified the comparison of separately tested CPT and VPT as a measure of modality-specific vulnerability. Contrary to the common belief, a focal compression sufficient to produce rapidly reversible conduction abnormalities affects the slow-conducting small myelinated fibers mediating cold perception before the fast-conducting large myelinated fibers transmitting vibration perception. The data document the order of modality-specific vulnerability of sensory nerve fibers to mild compression. The finding suggests that testing CPT, rather than VPT, provides a better QST to delineate rapidly reversible symptoms induced by compression.


Human Plasma IgG N-Glycome Profiles Reveal a Proinflammatory Phenotype in Chronic Thromboembolic Pulmonary Hypertension.
The pathological mechanism of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood, and inflammation has been reported to be one of its etiological factors. IgG regulates systemic inflammatory homeostasis, primarily through its N-glycans. Little is known about IgG N-glycosylation in CTEPH. We aimed to map the IgG N-glycome of CTEPH to provide new insights into its pathogenesis and discover novel markers and therapies. We characterized the plasma IgG N-glycome of patients with CTEPH in a discovery cohort and validated our results in an independent validation cohort using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Thereafter, we correlated IgG N-glycans with clinical parameters and circulating inflammatory cytokines in patients with CTEPH. Furthermore, we determined IgG N-glycan quantitative trait loci in CTEPH to reveal partial mechanisms underlying glycan changes. Decreased IgG galactosylation representing a proinflammatory phenotype was found in CTEPH. The distribution of IgG galactosylation showed a strong association with NT-proBNP (N-terminal pro-B-type natriuretic peptide) in CTEPH. In line with the glycomic findings, IgG pro-/anti-inflammatory N-glycans correlated well with a series of inflammatory markers and gene loci that have been reported to be involved in the regulation of these glycans or inflammatory immune responses. This is the first study to reveal the full signature of the IgG N-glycome of a proinflammatory phenotype and the genes involved in its regulation in CTEPH. Plasma IgG galactosylation may be useful for evaluating the inflammatory state in patients with CTEPH; however, this requires further validation. This study improves our understanding of the mechanisms underlying CTEPH inflammation from the perspective of glycomics.


Compression-induced pulsatile blood flow changes in human legs.
Initial and sustained (7-h) impacts of foot-to-knee compression bandaging on leg arterial pulsatile blood flow were assessed by nuclear magnetic resonance flowmetry in eight healthy supine subjects. A widely used bandaging method (zinc impregnated gauze + Coban) and a slight variant (Coban only) were applied one week apart to one leg. Blood flow was measured on each day of bandage application before and after bandaging and after 7 h of normal activity. Initial mean sub-bandage pressures (lateral gaiter) were between 28.4 and 28.9 mmHg but were significantly reduced after 7 h to 16.3-19.4 mmHg. Overall below-knee pulsatile blood perfusion was initially significantly increased by both methods mainly due to increased proximal blood flow. Bandaging was also associated with a decrease in blood perfusion of the nonbandaged control leg mainly due to a decrease in distal blood flow. Neither of these effects were sustained after 7 h. The fact that neither sub-bandage pressure nor blood flow was sustained may indicate a causal linkage, a concept consistent with the finding of a linear relationship between afternoon blood flow and sub-bandage pressure reductions. The implications of the present findings for venous ulcer therapy are speculative and based on the concept that arterial pulsatile flow augmentation is a positive feature. If so, more frequent bandage changes to provide transient flow stimulation or use of bandages to better maintain sub-bandage pressure to sustain flow increases may be useful.


The effect of polyvinylpyrrolidine on the stability of taurolidine.
In an aqueous solution, taurolidine reversibly degrades to taurultam, hydroxymethyltaurultam, taurineamide, and formaldehyde. The objectives of this research were to investigate the mechanism of polyvinylpyrrolidine (PVP)-induced taurolidine stabilization by measuring the effect of PVP on the rate and extent of formaldehyde release from taurolidine and its decomposition products, the ionization of taurineamide, and the NMR and FT-IR spectra of taurineamide. PVP was found to a) increase the rate constant for taurultam formation from taurineamide and formaldehyde, b) decrease the apparent pKa of taurineamide, and c) alter the NMR and FT-IR taurineamide spectra. The effect of PVP on the stability of taurolidine was to increase the stability of its primary degradation product, taurultam, which, in turn increased taurolidine stability because taurultam was reversibly formed from taurolidine. Furthermore, the increased stability of taurultam in acidic, aqueous PVP solutions was due to an increased rate of taurultam formation from its primary degradation products: taurineamide and formaldehyde. The rate constant for taurultam formation increased three-fold in the presence of 5% PVP. The rate increase was caused by the interaction of unprotonated taurineamide with PVP. The estimated taurineamide-PVP association constant was 1800 M-1. This interaction decreased the concentration of unreactive/protonated taurineamide while increasing the concentration of unprotonated/associated substrate which was found to be fivefold less reactive than the free/unprotonated amine.


Cargo sorting to lysosome-related organelles regulates siRNA-mediated gene silencing.
Mammals lacking BLOC-3 have impaired formation of melanosomes, a type of lysosome-related organelle (LRO), and, in earlier work, we found that a subunit of the BLOC-3 complex inhibits loading of Argonaute (Ago) proteins with small ribonucleic acids (RNAs) in Drosophila melanogaster cells. Small RNAs such as small interfering RNAs (siRNAs) direct Ago proteins to repress the stability of messenger RNA transcripts. In this paper, we show that BLOC-3 is required for biogenesis of Drosophila LROs called pigment granules. Other complexes that sort cargo to pigment LROs also negatively regulate siRNA activity. However, regulation is not obligately linked to biogenesis of LROs but instead to specific cargo-sorting processes. Negative regulation is also not linked to sorting into all LROs but only a specific class of pigment LRO. Thus, regulation of siRNA activity is tied to sorting of specific types of cargo to particular LROs.


Stroke volume and the three phase cardiac output rate relationship with ventricular pacing.
Knowledge of how stroke volume (SV), and hence cardiac output (CO), changes with ventricular pacing rate (R) constitutes a key aspect of sensor driven, variable rate pacemakers. It has been established that the relationship between CO and pacing rate exhibits three phases for rest and constant exercise. At low rates (phase 1), CO increases with increasing R; with additional rate increase (phase 2), CO either remains constant or increases slightly; and above some critical rate, CO decreases (phase 3). However, the nature of the relationship between SV and pacing rate has not been as clearly described. Therefore, the objectives of this study were (1) to describe and document the relationship between SV and R, and (2) to demonstrate the consequence of this relationship in terms of the three phase CO versus R relationship. In six anesthetized dogs, right ventricular SV was determined from pulmonary artery blood flow measured using an electromagnetic flow meter, and the right ventricle was paced over a range of rates. In general, SV decreased with increasing R, although the exact nature of the relationship varied from animal to animal. The results demonstrate that it is the manner in which SV decreases with increasing R that determines the three phase relationship between CO and R. The relationships described in this study have important implications for choosing pacing rates for patients receiving sensor driven, variable rate pacemakers.


[Sclerotherapy with 75% ethanol in the control of hemorrhage caused by peptic ulcer disease].
We present our experience using ethanol as sclerosant of non-variceal bleeding lesions of the upper digestive tract and the result of its hemostatic effect when compared with patients who received conventional medical treatment. Since January 1989, 48 patients admitted with active bleeding or signs of high risk for rebleeding (clot or visible vessel) were submitted to sclerosis. The historic control group included patients admitted before 1989, being both groups comparable in clinical and endoscopic characteristics. Surgery was performed in 5 cases of the sclerosis group (10.4%) versus 14 of the control group (37.8%). Five of the patients in the sclerotherapy group died, one of them due to upper G.I. bleeding as the primary cause. We dit not observe a statistically significant difference in hospital stay, transfusion requirements or mortality. There were no complications as a result of the method. Sclerotherapy was not immediately effective in 2 patients; three patients who rebled were subject to new sclerosis, which was effective in controlling bleeding in two of them. In conclusion, sclerosis is a safe and effective method to achieve hemostasis, diminishing the re-bleeding and the need for surgery in cases of digestive bleeding due to peptic ulcer disease. Future studies using larger samples could show decrease in mortality.


[On the involvement of the temporomandibular joint in rheumatoid arthritis].
64 patients with rheumatoid arthritis (RA) were examined for temporomandibular joint (TMJ) symptoms as well as for the severity and incidence of their symptoms. In detailed interviews, a total of 34 patients (53.1%) reported TMJ symptoms, the main complaints being problems during opening and closing of the mouth (45.2%). RA patients with TMJ symptoms differed significantly from those without TMJ symptoms (p < 0.01) in the duration (121.7 +/- 100.5 months vs. 37.1 +/- 27.6 months) and the state of activity of the basic disease. The patients subjectively evaluated the severity of the TMJ symptoms as mild to moderate (grade: 2-3; severity: 241 +/- 1.01). Almost 70% reported occasional symptoms, 22.5% frequent symptoms and 10.6% permanent symptoms (p < 0.01). 61.8% (21/34) of the patients showed no radiographic change in the shape of the TMJ condyle, whereas 11.8% (4/34) demonstrated a change on one side an 26.4% (9/34) a change on both sides. There was no difference in the severity of the TMJ symptoms between patients with an unchanged condyle (n = 21; severity: 2.33 +/- 0.96) and patients with changes in condylar shape (n = 13; severity: 2.5 +/- 1.12). A frequent involvement of the temporomandibular joint in RA can be considered certain. The symptoms, which were generally moderate, can cause a marked impairment of daily used functions, such as chewing and speaking.


[Establishment of retention time-dependent intelligent selected reaction monitoring mass spectrometric method and its application].
A method of liquid chromatographic retention time-dependent intelligent selected reaction monitoring mass spectrometry (iSRM MS) was established for the identification of targeted proteome, and was compared in detail with the method without liquid chromatographic retention time-dependent iSRM MS in the analysis results of different samples, such as the peptide mixtures from bovine serum albumin, six standard proteins or Thermoanaerobacter tengcongensis extract digested by trypsin. The results showed that the throughput of the identified peptides and the proteins was evidently increased with the method of liquid chromatographic retention time-dependent iSRM MS, especially in the complex sample such as Thermoanaerobacter tengcongensis extract. The coverage of the identified peptides and proteins from Thermoanaerobacter tengcongensis extract was reached 89.62% and 92.41% of the number of targeted peptides and proteins respectively. Higher sensitivity and reproducibility were also obtained. In addition, peptides with the same m/z but different retention times could be identified accurately when the method was used. With the higher throughput, better sensitivity and excellent reproducibility, the method of liquid chromatographic retention time-dependent iSRM MS can play an important role in the identification of targeted proteomes of complex biological samples in the future.


[Storage stability of 14 plasma proteins in ACD-AG banked blood].
In summarizing the results it can be stated that, when stored, the proteins haemopexin, alpha 1-antichymotrypsin, alpha 1-antitrypsin, which are rich of neuraminic acid, and IgA are predominantly characterized by a diminution of electrophoretic mobility and thus of concentration in electro-immunodiffusion, with the neuraminic acid content decreasing at the same time. These changes are probably caused by bacteria and/or virus neuraminidase. The decrease of pre-albumin concentration to be observed in radial-immunodiffusion and electro-immunodiffusion is caused by other mechanisms because pre-albumin contains no neuraminic acid. In accordance with these findings the most important changes of single proteins which can be measured by our equipment concern the percentage of non-proteins, whereas the antigen binding places will remain relatively stable during storage (ep. findings of radial immunodiffusion).


N,N,N',N'-Tetrakis(2-quinolylmethyl)-2-hydroxy-1,3-propanediamine (Htqhpn) as a supporting ligand for a low-valent (mu-O)2 tetranuclear manganese core.
A new heptadentate N6-O1 ligand, N,N,N',N'-tetrakis(2-quinolylmethyl)-2-hydroxy-1,3-propanediamine (Htqhpn), was synthesized and used to generate compounds with linearly ordered MnIIMnIIIMnIIIMnII tetranuclear cores. This is the lowest valent tetranuclear manganese complex that exhibits a (mu2-O)2Mn2 core in the molecule. The electron paramagnetic resonance and magnetic measurements of these tetranuclear complexes suggest moderately strong antiferromagnetic coupling for the central MnIII2 core, with weak coupling between the MnII and MnIII centers.


Heterotrophic feeding as a newly identified survival strategy of the dinoflagellate Symbiodinium.
Survival of free-living and symbiotic dinoflagellates (Symbiodinium spp.) in coral reefs is critical to the maintenance of a healthy coral community. Most coral reefs exist in oligotrophic waters, and their survival strategy in such nutrient-depleted waters remains largely unknown. In this study, we found that two strains of Symbiodinium spp. cultured from the environment and acquired from the tissues of the coral Alveopora japonica had the ability to feed heterotrophically. Symbiodinium spp. fed on heterotrophic bacteria, cyanobacteria (Synechococcus spp.), and small microalgae in both nutrient-replete and nutrient-depleted conditions. Cultured free-living Symbiodinium spp. displayed no autotrophic growth under nitrogen-depleted conditions, but grew when provided with prey. Our results indicate that Symbiodinium spp.'s mixotrophic activity greatly increases their chance of survival and their population growth under nitrogen-depleted conditions, which tend to prevail in coral habitats. In particular, free-living Symbiodinium cells acquired considerable nitrogen from algal prey, comparable to or greater than the direct uptake of ammonium, nitrate, nitrite, or urea. In addition, free-living Symbiodinium spp. can be a sink for planktonic cyanobacteria (Synechococcus spp.) and remove substantial portions of Synechococcus populations from coral reef waters. Our discovery of Symbiodinium's feeding alters our conventional views of the survival strategies of photosynthetic Symbiodinium and corals.


Immune response in addicts with chronic hepatitis C treated with interferon and ribavirin.
The role played by the immune system in the progression of chronic hepatitis C (CHC) is not completely clear. Opioids may facilitate the outbreak of infections through marked immunomodulating effects on the immune response against a virus. To asses if addicts can be treated successfully with interferon (IFN) during detoxification treatment, we evaluated some immune response mediators in addicts affected by CHC. A cohort of heroin users with CHC were enrolled during the detoxification period, divided into two groups and treated with IFN pegilate plus ribavirin (group A treated during methadone administration and group B treated at week 8 after methadone treatment completed). A group of patients with CHC and no history of drug addiction were enrolled as controls. Leukocyte subpopulation NK, CD4+, CD8+ and some cytokines Th1 (IFNgamma, interleukin [IL]2) and Th2 (IL-6, IL-10) were evaluated prior to, during and after methadone treatment. Sustained virological response was evaluated 24 weeks after antiviral treatment was completed. During methadone treatment, significantly (P < 0.05) higher cytokine Th1 and NK and lower cytokine Th2 levels were observed in groups A and B compared with levels obtained before treatment in the same groups. Relapse occurred at 56 +/- 8 weeks in 34/55 group A patients, at 24 +/- 8 weeks in 33/52 group B patients and at 24 +/- 4 weeks in group C, there being a significant difference (P < 0.05) between group A and B and between group A and C. No significant differences between all groups were detected in CD4+ and CD8+ cell counts. Our results revealed that drug addicts with CHC can be treated successfully with IFN pegilate and ribavirin. This therapy can be recommended during the early phase of detoxification treatment to achieve a sustained response.


Pattern of 4-thiouridine-induced cross-linking in 16S ribosomal RNA in the Escherichia coli 30S subunit.
The locations of RNA-RNA cross-links in 16S rRNA were determined after in vivo incorporation of 4-thiouridine (s(4)U) into RNA in a strain of Escherichia coli deficient in pyrimidine synthesis and irradiation at >320 nm. This was done as an effort to find RNA cross-links different from UVB-induced cross-links that would be valuable for monitoring the 30S subunit in functional complexes. Cross-linked 16S rRNA was separated on the basis of loop size, and cross-linking sites were identified by reverse transcription, RNase H cleavage, and RNA sequencing. A limited number of RNA-RNA cross-links in nine regions were observed. In five regions-s(4)U562 x C879-U884, s(4)U793 x A1519, s(4)U1189 x U1060-G1064, s(4)U1183 x A1092, and s(4)U991 x C1210-U1212-the s(4)U-induced cross-links are similar to UVB-induced cross-links observed previously. In four other regions-s(4)U960 x A1225, s(4)U820 x G570, s(4)U367 x A55-U56, and s(4)U239 x A120-the s(4)U-induced cross-links are different from UVB-induced cross-links. The pattern of cross-linking is not limited by the distribution of s(4)U, because there are at least 112 s(4)U substitution sites in the 16S rRNA. The relatively small number of s(4)U-mediated cross-links is probably determined by the organization of the RNA in the 30S subunit, which allows RNA conformational flexibility needed for cross-link formation in just a limited region.


Imatinib: paradigm or anomaly?
The introduction of imatinib (Gleevec, Glivec, formerly STI571), an agent targeting the causative molecular event in chronic myeloid leukemia (CML) has been heralded as a major advance in the treatment of cancer. Certainly, the clinical trials with imatinib have validated the concept that a precise understanding of the pathogenesis of a cancer can lead to more effective and less toxic therapies. Despite the success of imatinib, there remains much skepticism that this paradigm will be applicable to more complicated solid tumors. Whether this skepticism is appropriately deserved will be discussed.


Should medical students be routinely offered BCG vaccination?
BCG vaccination is no longer routinely offered to all medical students in Victoria. Practices in Australia's 15 medical schools vary widely with respect to BCG vaccination and surveillance for tuberculosis (TB) infection during the medical course. Health care workers can be exposed to TB in Australian hospitals, but the risk is much higher if they undertake work in countries with a high prevalence of TB, such as during student electives. BCG vaccination is safe, cheap and protects 50% or more of recipients from active TB, including multidrug-resistant TB. Protection is long-lasting, requires only a single dose, and there is new evidence that BCG may prevent primary infections, not just active disease. Although BCG vaccination interferes with the interpretation of the tuberculin skin test (TST), newer tests (QuantiFERON-TB Gold, T-SPOT.TB) are unaffected by BCG vaccination. We propose a standard approach for all Australian medical students that includes screening with TST and QuantiFERON-TB Gold/T-SPOT.TB at course entry, and recommending BCG vaccination for students who test negative, provided they have not previously received BCG vaccine.


Dermatophilosis of Alpine Chamois (Rupicapra rupicapra) in Italy.
A proliferative dermatitis similar to the condition generally referred to as strawberry footrot was observed in two Alpine chamois (Rupicapra rupicapra) from Eastern Alps, Italy. Branching septated filaments and packets of PAS-positive coccoid organisms were observed in histological sections of the affected skin. The actinomycete, Dermatophilus congolensis, was isolated from crusted lesions in one chamois. As wild ruminants are presumed to be a reservoir of infection in the Alpine area, the authors discuss the potential role of chamois in the epidemiology of dermatophilosis.


Female Reproductive Factors and Differentiated Thyroid Cancer.
Differentiated thyroid cancer (DTC) is markedly more common in women than men, the highest female-to-male ratio being recorded during the reproductive period. This evidence has led to the suggestion that female hormonal and reproductive factors may account for the observed DTC gender disparity. This review focuses on current evidence on the risk of DTC in conjunction with major female reproductive factors, including the impact of pregnancy on DTC occurrence and progression/recurrence. Overall, studies exploring the link between the risk of DTC and menstrual and menopausal factors, oral contraceptives and/or hormone replacement therapy, showed these associations, if any, to be generally weak. Nonetheless, there is some evidence that higher levels of exposure to estrogens during reproductive years may confer an increased risk of DTC. As far as pregnancy is concerned, it is unclear whether a potential association between parity and risk of DTC actually exists, and whether it is enhanced in the short-term following delivery. A possible role for pregnancy-related factors in DTC progression has been recently suggested by some reports, the results of which are consistent with a worse outcome in the short-term of women diagnosed with DTC during gestation compared to non-pregnant control patients. Also, some progression of disease has been described in women with structural evidence of disease prior to pregnancy. However, there seems to be no impact from pregnancy in DTC-related death or overall survival. Several in vitro and animal studies have evaluated the influence of estrogens (E) and estrogen receptors (ERs) on thyroid cell proliferation. Presently available data are indicative of a role of E and ERs in thyroid cancer growth, although considerable discrepancies in respect to ER expression patterns in thyroid cancer tissues actually exist. Further studies providing more direct evidence on the possible role of E and of placental hormones and growth factors on thyroid growth may expand our knowledge on the mechanisms beyond the gender disparity of proliferative thyroid diseases.


[Utilization of embryo development technique of Brachydanio rerio to evaluating toxicity on various chemicals].
The application of Brachydanio rerio embryo development technique to research on environmental science was summarized in this paper. This testing technique was approved as one of standard methods for chemical toxicity test, especially for teratogensis, by international organizations (OECD, DIN). There are many advantages of this testing, e.g., low cost, easy operation, high sensitivity and multiple sensible endpoints, comparing with other toxicity testing. Also, it was used to judge toxic mechanism of chemicals. The embryo development of zebrafish can be affected obviously by heavy metal, pesticide, organic reagent and complex chemicals. Among them, Cu and Hg appeared stronger toxicity, and Cr was weaker for heavy metals. TPTA and Lindane were higher toxicity within pesticide, and they were higher toxicity if the organic reagent with one or more halogen substituent(s) and aminobenzene. These results were correspondent with other toxicity testing, and it showed higher sensitivity, especially a sublethal endpoint was selected. Therefore, it can be expected to test toxicity and teratogensis on mixed pollutant monitoring.


Lacidipine Amorphous Solid Dispersion Based on Hot Melt Extrusion: Good Miscibility, Enhanced Dissolution, and Favorable Stability.
The present study aimed to increase the in vitro dissolution rate of lacidipine, a poorly water-soluble drug, by formulating amorphous solid dispersions (ASDs) using hot-melt extrusion (HME). Differential scanning calorimetry, powder X-ray diffraction, polarized light microscopy, and Fourier transform infrared were used to characterize the optimal formulations and evaluate the physical stability for the stress test. Film-casting method and hot-stage microscopy were applied to study the miscibility of lacidipine and the drug carriers. In vitro dissolution tests were conducted as the final evaluation index. The optimal formulations were successfully obtained with Soluplus and PVP VA64 at a drug/carrier ratio of 1:10 (w/w), Fourier transform infrared studies revealed the hydrogen bonding between drug and polymers, and in vitro dissolution rates of the optimal formulations were extremely enhanced compared to bulk lacidipine and physical mixtures, similar with that of the commercial tablet. The ASD formulated with Soluplus showed better physical stability than that with PVP VA64. A strong hydrogen bonding and good drug-polymer miscibility were essential to hinder the recrystallization of lacidipine ASDs. In conclusion, the lacidipine ASD formulated with Soluplus showed a significant increase in in vitro dissolution rate and favorable physical stability in the stress test.


Protectin DX suppresses hepatic gluconeogenesis through AMPK-HO-1-mediated inhibition of ER stress.
Several studies have shown that protectins, which are ω-3 fatty acid-derived proresolution mediators, may improve insulin resistance. Recently, protectin DX (PDX) was documented to attenuate insulin resistance by stimulating IL-6 expression in skeletal muscle, thereby regulating hepatic gluconeogenesis. These findings made us investigate the direct effects of PDX on hepatic glucose metabolism in the context of diabetes. In the current study, we show that PDX regulates hepatic gluconeogenesis in a manner distinct from its indirect glucoregulatory activity via IL-6. We found that PDX stimulated AMP-activated protein kinase (AMPK) phosphorylation, thereby inducing heme oxygenase 1 (HO-1) expression. This induction blocked hepatic gluconeogenesis by suppressing endoplasmic reticulum (ER) stress in hepatocytes under hyperlipidemic conditions. These effects were significantly dampened by silencing AMPK or HO-1 expression with small interfering RNA (siRNA). We also demonstrated that administration of PDX to high fat diet (HFD)-fed mice resulted in increased hepatic AMPK phosphorylation and HO-1 expression, whereas hepatic ER stress was substantially attenuated. Furthermore, PDX treatment suppressed the expression of gluconeogenic genes, thereby decreasing blood glucose levels in HFD-fed mice. In conclusion, our findings suggest that PDX inhibits hepatic gluconeogenesis via AMPK-HO-1-dependent suppression of ER stress. Thus, PDX may be an effective therapeutic target for the treatment of insulin resistance and type 2 diabetes through the regulation of hepatic gluconeogenesis.


New species, notes and new records of Trichogramma (Hymenoptera: Trichogrammatidae) in Brazil.
Two new species of Trichogramma are described: Trichogramma piracicabense sp. nov. and T. valmiri sp. nov. Additionally, T. manicobai from eggs of the cassava hornworm Erinnyis ello is redescribed, and new records on the distribution and host associations of species of Trichogramma from Brazil are presented.


Cancer incidence and mortality in Shandong province, 2012.
Population-based cancer registration data in 2012 from all available cancer registries in Shandong province were collected by Shandong Center for Disease Control and Prevention (SDCDC). SDCDC estimated the numbers of new cancer cases and cancer deaths in Shandong province with compiled cancer incidence and mortality rates. In 2015, there were 21 cancer registries submitted data of cancer incidence and deaths occurred in 2012. All the data were checked and evaluated based on the National Central Cancer Registry (NCCR) criteria of data quality. Qualified data from 15 registries were used for cancer statistics analysis as provincial estimation. The pooled data were stratified by area (urban/rural), gender, age group (0, 1.4, 5.9, 10.14, …, 85+ years) and cancer type. New cancer cases and deaths were estimated using age-specific rates and corresponding provincial population in 2012. The Chinese census data in 2000 and Segi's population were applied for age-standardized rates. All the rates were expressed per 100,000 person-year. Qualified 15 cancer registries (4 urban and 11 rural registries) covered 17,189,988 populations (7,486,039 in urban and 9,703,949 in rural areas). The percentage of cases morphologically verified (MV%) and death certificate-only cases (DCO%) were 66.12% and 2.93%, respectively, and the mortality to incidence rate ratio (M/I) was 0.60. A total of 253,060 new cancer cases and 157,750 cancer deaths were estimated in Shandong province in 2012. The incidence rate was 263.86/100,000 (303.29/100,000 in males, 223.23/100,000 in females), the age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 192.42/100,000 and 189.50/100,000 with the cumulative incidence rate (0.74 years old) of 22.07%. The cancer incidence, ASIRC and ASIRW in urban areas were 267.64/100,000, 195.27/100,000 and 192.02/100,000 compared to 262.32/100,000, 191.26/100,000 and 188.48/100,000 in rural areas, respectively. The cancer mortality was 164.47/100,000 (207.42/100,000 in males, 120.23/100,000 in females), the age-standardized incidence rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 117.54/100,000 and 116.90/100,000, and the cumulative mortality rate (0.74 years old) was 13.53%. The cancer mortality, ASMRC and ASMRW were 141.59/100,000, 101.17/100,000 and 100.33/100,000 in urban areas, and 173.79/100,000, 124.20/100,000 and 123.64/100,000 in rural areas, respectively. Cancers of the lung, stomach, liver, esophagus, colorectum, female breast, brain, leukemia, bladder and pancreas were the most common cancers, accounting for about 82.12% of all cancer new cases. Lung cancer, stomach cancer, liver cancer, esophageal cancer, colorectal cancer, female breast cancer, pancreatic cancer, brain tumor, leukemia and lymphoma were the leading causes of cancer death, accounting for about 89.01% of all cancer deaths. The cancer spectrum showed difference between urban and rural, males and females both in incidence and mortality rates. Cancer surveillance information in Shandong province is making great progress with the increasing number of cancer registries, population coverage and the improving data quality. Cancer registration plays a fundamental role in cancer control by providing basic information on population-based cancer incidence, mortality, survival and time trend. The disease burden of cancer is serious in Shandong province, and so cancer prevention and control in Shandong province should be enhanced including health education, health promotion, cancer screening and cancer care services.


Wheel-like Mn(II)6 and Ni(II)6 complexes from the use of 2-pyridinealdoxime and carboxylates.
The employment of 2-pyridinealdoxime, (py)C(H)NOH, in nickel(II) and manganese(II) carboxylate chemistry under solvothermal conditions is reported. The syntheses, crystal structures and magnetochemical characterization (for two representative compounds) are described for [Ni(6)(O(2)CMe)(6){(py)C(H)NO}(6)].H(2)O (1.H(2)O), [Ni(6)(O(2)CPh)(6){(py)C(H)NO}(6)].2EtOH (2.2EtOH), [Ni(6){(4-Cl)O(2)CPh}(6){(py)C(H)NO}(6)].2EtOH (3.2EtOH) and [Mn(6)(O(2)CMe)(6){(py)C(H)NO}(6)].H(2)O (4.H(2)O), where (4-Cl)PhCO(2)(-) is 4-chlorobenzoate. The reactions of M(O(2)CMe)(2).4H(2)O (M = Ni, Mn) with one equivalent of (py)C(H)NOH in EtOH at 120 degrees C under autogenous pressure give isostructural 1.H(2)O and 4.H(2)O. Complexes 2.2EtOH and 3.2EtOH were obtained from the 1 : 1 : 1 Ni(O(2)CMe)(2).4H(2)O/{(py)C(H)NOH/(X)PhCO(2)H reaction mixtures in EtOH under solvothermal conditions (X = H, 4-Cl). The structurally similar clusters 1-4 have a wheel-like topology with the six metal ions in a chair conformation. Each metal site is bound to four oxygen and two nitrogen atoms; the donor atoms come from two carboxylate oxygens, two oximate oxygens, one pyridyl nitrogen and one oximate nitrogen atom. The carboxylate ligands show the syn, syn eta(1):eta(1):mu mode, while the (py)C(H)NO(-) ions behave as eta(1):eta(1):eta(2):mu(3) ligands. Each metal...metal vector is bridged by one carboxylate group, one mu-O derived from a (py)C(H)NO(-) ligand and by one diatomic oximate-NO- group from an adjacent (py)C(H)NO(-) group. The IR spectra of the complexes are discussed in terms of the coordination modes of the ligands. Variable-temperature, solid-state dc magnetic susceptibility studies were carried out on polycrystalline samples of 1 and 4. The data in the 2.0-300 K range have been fit to a model with one J value revealing moderate (1) or weak (2) antiferromagnetic M(II)...M(II) exchange interactions. This work demonstrates the synthetic potential of combining (py)C(H)NOH with carboxylate ligands and the usefulness of solvothermal techniques in 3d-metal cluster chemistry.


Quantum Fluctuation Dynamics of Dispersive Superradiant Pulses in a Hybrid Light-Matter System.
We consider theoretically a driven-dissipative quantum many-body system consisting of an atomic ensemble in a single-mode optical cavity as described by the open Tavis-Cummings model. In this hybrid light-matter system, the interplay between coherent and dissipative processes leads to superradiant pulses with a buildup of strong correlations, even for systems comprising hundreds to thousands of particles. A central feature of the mean-field dynamics is a self-reversal of two spin degrees of freedom due to an underlying time-reversal symmetry, which is broken by quantum fluctuations. We demonstrate a quench protocol that can maintain highly non-Gaussian states over long timescales. This general mechanism offers interesting possibilities for the generation and control of complex fluctuation patterns, as suggested for the improvement of quantum sensing protocols for dissipative spin amplification.


Nonlinear surface waves at the interfaces of left-handed electromagnetic media.
We report the existence of families of nonlinear TE-polarized surface waves propagating along the interface between different conventional and left-handed electromagnetic media as well as between two left-handed media. Both nonlinear/nonlinear and linear/nonlinear interfaces are considered. The constraints for the mode existence are identified and the energy flow associated with the surface modes is calculated.


Physiological and Transcriptional Changes of Three Citrus Rootstock Seedlings under Iron Deficiency.
Iron is an essential micronutrient for plants, and plants have evolved adaptive mechanisms to improve iron acquisition from soils. Grafting on iron deficiency-tolerant rootstock is an effective strategy to prevent iron deficiency-chlorosis in fruit-tree crops. To determine the mechanisms underlying iron uptake in iron deficiency, two iron deficiency-tolerant citrus rootstocks, Zhique (ZQ) and Xiangcheng (XC), as well as iron deficiency-sensitive rootstock trifoliate orange (TO) seedlings were studied. Plants were grown in hydroponics system for 100 days, having 50 μM iron (control) and 0 μM iron (iron deficiency) nutrient solution. Under iron deficiency, more obvious visual symptoms of iron chlorosis were observed in the leaves of TO, whereas slight symptoms were observed in ZQ and XC. This was further supported by the lower chlorophyll concentration in the leaves of TO than in leaves of ZQ and XC. Ferrous iron showed no differences among the three citrus rootstock roots, whereas ferrous iron was significantly higher in leaves of ZQ and XC than TO. The specific iron absorption rate and leaf iron proportion were significantly higher in ZQ and XC than in TO, suggesting the iron deficiency tolerance can be explained by increased iron uptake in roots of ZQ and XC, allowed by subsequent translocation to shoots. In transcriptome analysis, 29, 298, and 500 differentially expressed genes (DEGs) in response to iron deficiency were identified in ZQ, XC, and TO, respectively (Fold change ≥ 2 and Probability ≥ 0.8 were used as thresholds to identify DEGs). A Gene Ontology analysis suggested that several genotype-specific biological processes are involved in response to iron deficiency. Genes associated with cell wall biosynthesis, ethylene and abscisic acid signal transduction pathways were involved in iron deficiency responses in citrus rootstocks. The results of this study provide a basis for future analyses of the physiological and molecular mechanisms of the tolerance of different citrus rootstocks to iron deficiency.


Predictors of successful acetylsalicylic acid resistance suppression after percutaneous coronary revascularisation.
There is no established management of resistance to acetylsalicylic acid (ASA) in patients with coronary artery disease (CAD). We hypothesised that simply doubling the usual daily dose of ASA could be effective in overcoming ASA resistance. Our study comprised 40 subjects with CAD (male 67.5%, mean age 60.5 ± 8.8 years, mean body mass index 26.9 ± 2.7 kg/m² and median aspirin reaction unit [ARU] value obtained with a Verify Now Aspirin Test 612 [573-634]) with resistance to 75 mg/daily ASA defined as ARU ≥ 550. According to the overcoming of resistance or lack there of in a repeated test after four weeks of 150 mg daily ASA treatment, we defined two subsets: subjects who regained ASA sensitivity, and those who did not. Successful overcoming of ASA resistance was observed in 62.5% of patients. Multivariate analysis regression confirmed that two variables independently determined successful ASA resistance suppression: male gender (OR 6.88; 95% CI 1.29-36.75; p = 0.024), and ARU for 75 mg daily (OR 0.97 per unit at 75 mg; 95% CI 0.94-0.99; p = 0.039). ROC analysis indicated that the threshold value at which ARU at 75 mg ASA treatment was predictive of successful ASA resistance overcoming was ≤ 608 ARU. Using a simple point score (one point for male gender and one for initial ARU ≤ 608), we found that ASA resistance was overcome in 8%, 36% and 56% of patients, when zero, any single, or two predictors were present. ASA resistance overcoming by dose doubling can be achieved more often in males and in subjects with lower ARU value at ASA 75 mg.


Iodine-131 induces apoptosis in human cardiac muscle cells through the p53/Bax/caspase-3 and PIDD/caspase-2/ t‑BID/cytochrome c/caspase-3 signaling pathway.
The aim of this study was to elucidate the effects of iodine-131 on the induction of apoptosis in human cardiac muscle cells and the underlying molecular mechanisms. We found that iodine-131 reduced cell proliferation, induced apoptosis, induced p53, PIDD, t-BID (mitochondria) protein expression, suppressed cytochrome c (mitochondria) protein expression, and increased Bax protein expression, and promoted caspase-2, -3 and -9 expression levels in human cardiac muscle cells. Meanwhile, si-p53 inhibited the effects of iodine-131 on the reduction in cell proliferation and induction of apoptosis in human cardiac muscle cells through regulation of Bax/cytochrome c/caspase-3 and PIDD/caspase‑2/t-BID/cytochrome c/caspase-3 signaling pathway. After si-Bax reduced the effects of iodine-131, it reduced cell proliferation and induced apoptosis in human cardiac muscle cells through the cytochrome c/caspase-3 signaling pathway. However, si-caspase-2 also reduced the effects of iodine-131 on the reduction of cell proliferation and induction of apoptosis in human cardiac muscle cells through the t-BID/cytochrome c/caspase-3 signaling pathway. These findings demonstrated that iodine-131 induces apoptosis in human cardiac muscle cells through the p53/Bax/caspase-3 and PIDD/caspase-2/t-BID/cytochrome c/caspase-3 signaling pathway.


Site of action of the general anesthetic propofol in muscarinic M1 receptor-mediated signal transduction.
Although a potential target site of general anesthetics is primarily the GABA A receptor, a chloride ion channel, a previous study suggested that the intravenous general anesthetic propofol attenuates the M1 muscarinic acetylcholine receptor (M1 receptor)-mediated signal transduction. In the present study, we examined the target site of propofol in M1 receptor-mediated signal transduction. Two-electrode voltage-clamp method was used in Xenopus oocytes expressing both M1 receptors and associated G protein alpha subunits (Gqalpha). Propofol inhibited M1 receptor-mediated signal transduction in a dose-dependent manner (IC50 = 50 nM). Injection of guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) into oocytes overexpressing Gqalpha was used to investigate direct effects of propofol on G protein coupled with the M1 receptor. Propofol did not affect activation of Gqalpha-mediated signal transduction with the intracellular injection of GTPgammaS. We also studied effects of propofol on l-[N-methyl-3H]scopolamine methyl chloride ([3H]NMS) binding and M1 receptor-mediated signal transduction in mammalian cells expressing M1 receptor. Propofol inhibited the M1 receptor-mediated signal transduction but did not inhibit binding of [3H]NMS. Effects of propofol on Gs- and Gi/o-coupled signal transduction were investigated, using oocytes expressing the beta2 adrenoceptor (beta2 receptor)/cystic fibrosis transmembrane conductance regulator or oocytes expressing the M2 muscarinic acetylcholine receptor (M2 receptor)/Kir3.1 (a member of G protein-gated inwardly rectifying K(+) channels). Neither beta2 receptor-mediated nor M2 receptor-mediated signal transduction was inhibited by a relatively high concentration of propofol (50 microM). These results indicate that propofol inhibits M1 receptor-mediated signal transduction by selectively disrupting interaction between the receptor and associated G protein.


Adversarial Learning of Knowledge Embeddings for the Unified Medical Language System.
Incorporating the knowledge encoded in the Unified Medical Language System (UMLS) in deep learning methods requires learning knowledge embeddings from the knowledge graphs available in UMLS: the Metathesaurus and the Semantic Network. In this paper we present a technique using Generative Adversarial Networks (GANs) for learning UMLS embeddings and showcase their usage in a clinical prediction model. When the UMLS embeddings are available, the predictions improve by up to 6.9% absolute F1 score.


The asymmetric dialkylzinc addition to imines catalyzed by [2.2]paracyclophane-based N,O-ligands.
The first highly enantioselective dialkylzinc addition to imines in the presence of catalytic amounts of N,O-ligands is reported. N-formyl-alpha-(p-tolysulfonyl)benzylamines are the readily available starting materials easily obtained in a one-pot synthesis from benzaldehydes, formamide, and p-tolylsulfinic acid. Upon deprotonation, the sulfinate is eliminated to give the acyl imine. The acyl imines further react with alkylzinc reagents in the presence of catalytic amounts of [2.2]paracyclophane-based N,O-ligands L yielding the alkylated N-(1-phenylpropyl)formamides with excellent yields and enantioselectivities.


Beyond the Binary: Differences in Eating Disorder Prevalence by Gender Identity in a Transgender Sample.
Purpose: To investigate whether the prevalence of eating disorders (EDs) differs across diverse gender identity groups in a transgender sample. Methods: Secondary analysis of data from Project VOICE, a cross-sectional study of stress and health among 452 transgender adults (ages 18-75 years) residing in Massachusetts. Age-adjusted logistic regression models were fit to compare the prevalence of self-reported lifetime EDs in female-to-male (FTM), male-to-female (MTF), and gender-nonconforming participants assigned male at birth (MBGNC) to gender-nonconforming participants assigned female at birth (FBGNC; referent). Results: The age-adjusted odds of self-reported ED in MTF participants were 0.14 times the odds of self-reported ED in FBGNC participants (p=0.022). In FTM participants, the age-adjusted odds of self-reported ED were 0.46 times the odds of self-reported ED in FBGNC participants, a marginally significant finding (p=0.068). No statistically significant differences in ED prevalence were found for MBGNC individuals. Conclusions: Gender nonconforming individuals assigned a female sex at birth appear to have heightened lifetime risk of EDs relative to MTF participants. Further research into specific biologic and psychosocial ED risk factors and gender-responsive intervention strategies are urgently needed. Training clinical providers and ensuring competency of treatment services beyond the gender binary will be vital to addressing this disparity.


Neuroendocrine-immune system in patients with rheumatoid arthritis.
Abstract The neuroendocrine-immune system plays an important role in maintaining homeostasis. Since patients with rheumatoid arthritis (RA) tend to be exposed to long-term physical and psychological stress during the course of the disease, it is hypothesized that their neuroendocrine-immune system will become dysregulated. In order to understand the disturbances in the neuroendocrine-immune systems objectively, we measured and compared various components of the peripheral blood which were considered to reflect the state of these systems, in patients with RA and in control individuals. The serum levels of norepinephrine, interleukin-6 (IL-6), and the CD4/CD8 ratio were higher, whereas the levels of β-endorphin, adrenocorticotropic hormone, and NK cell activity were lower in the RA subjects than in the control subjects. On the other hand, the serum levels of methionine-enkephalin, epinephrine, corticotropin-releasing factor, cortisol, and CD57 were not significantly different in the two groups. In addition, we demonstrated the effects of hearty laughter, deep emotion with tears, or general anesthesia on the neuroendocrine-immune system. What need the most attention are changes in the IL-6 levels of RA patients. Serum IL-6 levels in RA were significantly higher than in controls, and fell rapidly to as low as half of their initial value after a bout of hearty laughter. Our results suggest that adequate mental intervention might serve to modulate the neuroendocrine-immune system of RA patients which had failed for various reasons.


ROS-responsive activatable photosensitizing agent for imaging and photodynamic therapy of activated macrophages.
The optical properties of macrophage-targeted theranostic nanoparticles (MacTNP) prepared from a Chlorin e6 (Ce6)-hyaluronic acid (HA) conjugate can be activated by reactive oxygen species (ROS) in macrophage cells. MacTNP are nonfluorescent and nonphototoxic in their native state. However, when treated with ROS, especially peroxynitrite, they become highly fluorescent and phototoxic. In vitro cell studies show that MacTNP emit near-infrared (NIR) fluorescence inside activated macrophages. The NIR fluorescence is quenched in the extracellular environment. MacTNP are nontoxic in macrophages up to a Ce6 concentration of 10 μM in the absence of light. However, MacTNP become phototoxic upon illumination in a light dose-dependent manner. In particular, significantly higher phototoxic effect is observed in the activated macrophage cells compared to human dermal fibroblasts and non-activated macrophages. The ROS-responsive MacTNP, with their high target-to-background ratio, may have a significant potential in selective NIR fluorescence imaging and in subsequent photodynamic therapy of atherosclerosis with minimum side effects.


A diquat-containing macrocyclic anion acceptor in pure water.
By taking advantage of a newly developed self-assembly approach based on oxime condensation, we successfully obtained a tetracationic macrocycle bearing two diquats in acidic aqueous media in a high yield. The ring is able to accommodate HPO42- and HCO3- in pure water.


[Modeling of drug-drug interactions between omeprazole and erythromycin with cytochrome P450 3A4 in vitro assay].
In the present study the electrochemical system based on recombinant cytochrome P450 3A4 (CYP3A4) was used for the investigation of potential drug-drug interaction between medicinal preparations employed for Helicobacter pylori eradication therapy. Drug interactions were demonstrated in association of omeprazole as a proton pump inhibitor (PPI) and macrolide antibiotic erythromycin during cytochrome P450 3A4-mediated metabolism. It was shown that in the presence of omeprazole the rate of N-demethylase activity of CYP3A4 to erythromycin measured by means of product (formaldehyde) formation decreased. Mass-spectrometry analysis of omeprazole sulfone as a CYP3A4-mediated metabolite demonstrated the absence of erythromycin influence on CYP3A4-dependent omeprazole metabolism. This phenomenon may be explained by lower spectral dissociation constant of CYP3A4-omeprazole complex (Kd = 18±2 μM) than that of CYP3A4-erythromycin complex (Kd = 52 μM). Using the electrochemical model of electrochemically-driven drug metabolism it is possible to register CYP3A4-mediated catalytic conversion of certain drugs. In vitro experiments of potential CYP3A4-mediated drug-drug interactions are in accordance with in silico modeling with program PASS and PoSMNA descriptors in the case of omeprazole/erythromycin combinations.


Distributed actin turnover in the lamellipodium and FRAP kinetics.
Studies of actin dynamics at the leading edge of motile cells with single-molecule speckle (SiMS) microscopy have shown a broad distribution of EGFP-actin speckle lifetimes and indicated actin polymerization and depolymerization over an extended region. Other experiments using FRAP with the same EGFP-actin as a probe have suggested, by contrast, that polymerization occurs exclusively at the leading edge. We performed FRAP experiments on XTC cells to compare SiMS to FRAP on the same cell type. We used speckle statistics obtained by SiMS to model the steady-state distribution and kinetics of actin in the lamellipodium. We demonstrate that a model with a single diffuse actin species is in good agreement with FRAP experiments. A model including two species of diffuse actin provides an even better agreement. The second species consists of slowly diffusing oligomers that associate to the F-actin network throughout the lamellipodium or break up into monomers after a characteristic time. Our work motivates studies to test the presence and composition of slowly diffusing actin species that may contribute to local remodeling of the actin network and increase the amount of soluble actin.


[Anti-hyperlipidemic agents].
There are several drugs for hyperlipidemia except for statin and fibrate. Resin is a commonly used drug for hypercholesterolemia and is known to very useful for the prevention of coronary heart disease(CHD). Probucol is also used for hypercholesterolemia and recently is known that it prevent the restenosis of the coronary artery after PTCA. Nicotinic acid is used for hypertriglyceridemia and hypercholesterolemia, both. It is also known to very useful for the prevention of CHD. Eicosapentaenoic acid is effective for hypertriglyceridemia and also shows an inhibition of platelets aggregation. These drugs as well as statin and fibrate are used in combination with each other for severe hyperlipidemia.


Synthesis and turnover of collagen precursors in rabbit skin.
1. The rate of synthesis of [(14)C]hydroxyproline by rabbit skin was studied in vitro and in vivo. 2. The soluble collagen fractions were shown to have a very rapid turnover. The 0.15m-sodium chloride-extractable collagen showed t((1/2)) values of 1.2hr. in vitro and 12hr. in vivo. The 0.5m-sodium chloride-extractable collagen exhibited a t((1/2)) value of 20hr. in vivo. 3. Under the conditions used it was not possible to obtain radioactive insoluble collagen in vitro. 4. A significant amount of soluble collagen is lost before it becomes insoluble. 5. These observations may help to explain why large amounts of peptide-bound hydroxyproline appear in the urine during periods of rapid collagen synthesis.


Coarse-grained force field for simulating polymer-tethered silsesquioxane self-assembly in solution.
A coarse-grained model has been developed for simulating the self-assembly of nonyl-tethered polyhedral oligomeric silsesquioxane (POSS) nanoparticles in solution. A mapping scheme for groups of atoms in the atomistic molecule onto beads in the coarse-grained model was established. The coarse-grained force field consists of solvent-mediated effective interaction potentials that were derived via a structural-based coarse-graining numerical iteration scheme. The force field was obtained from initial guesses that were refined through two different iteration algorithms. The coarse-graining scheme was validated by comparing the aggregation of POSS molecules observed in simulations of the coarse-grained model to that observed in all-atom simulations containing explicit solvent. At 300 K the effective coarse-grained potentials obtained from different initial guesses are comparable to each other. At 400 K the differences between the force fields obtained from different initial guesses, although small, are noticeable. The use of a different iteration algorithm employing identical initial guesses resulted in the same overall effective potentials for bare cube corner bead sites. In both the coarse-grained and all-atom simulations, small aggregates of POSS molecules were observed with similar local packings of the silsesquioxane cages and tether conformations. The coarse-grained model afforded a savings in computing time of roughly two orders of magnitude. Further comparisons were made between the coarse-grained monotethered POSS model developed here and a minimal model developed in earlier work. The results suggest that the interactions between POSS cages are long ranged and are captured by the coarse-grained model developed here. The minimal model is suitable for capturing the local intermolecular packing of POSS cubes at short separation distances.


Accuracy and resolution power of aerosol-derived airway morphometry in a simple lung model.
Aerosol-derived airway morphometry (ADAM) uses sedimentational deposition of monodisperse aerosol particles during breathhold to estimate intrapulmonary air-space dimensions. To determine the accuracy and resolution power of this technique a simple physical lung model comprised of uniform glass beads was investigated. Using the chordlength model, aerosol recovery from this porous medium was calculated by computer simulation of the geometrical structure of air-spaces between glass beads. The results of this calculation were then compared with experimental data: Calculated and measured air-space dimensions differ less than 2% for particles with diameters above about 1 micron. The measured air-space dimension can be described geometrically by the mean chordlength of the porous medium. To estimate the resolution power of ADAM, a defined change in air-space dimensions represented by a horizontal air slit was introduced into the porous medium. This air slit induces a marked increase of measured air-space dimensions. The volumetric width of this increase is the higher the deeper the slit is situated within the medium. Intercomparison of these data with the results of aerosol bolus dispersion measurements suggests that the resolution power of ADAM is decreased by the same mechanisms that increase dispersion of aerosol boluses, demonstrating the close relationship between both methods.


[CERVICAL CANCER IN ISRAEL 2016: FACTS, INSIGHTS AND THOUGHTS FOR THE FUTURE].
The natural history of precancerous lesions and cervical cancer in Israeli women differs from that reported in the world. In 2011, 244 women were diagnosed in Israel with invasive cervical cancer, with the mortality of 79 women. The incidence of cervical cancer in Israel is about 5 new cases per year per 100,000 women (5.4 Jewish, 3.2 Arab). This figure is very low compared with statistics presented in other countries and has not changed over the last decades. The vast majority of Israeli women were diagnosed due to symptoms and not following Pap smear screening. The mortality rate in Israel is similar to that of other OECD countries. In Israel, 71% of patients survive five years or more, the rate is not significantly different from the percentage of survival of other OECD countries. Over half of the Israeli patients are diagnosed in the late stage disease. This delay in cervical cancer diagnosis is probably due to the lack of a national screening program. We recommend more efficient routing of national expenditure for cervical cancer screening and prevention in Israel, scanning asymptomatic women and targeting disadvantaged populations. By applying the proposed screening strategy, redirection of resources will reduce cervical cancer morbidity and mortality, and will increase the percentage of women from low socioeconomic populations tested in Israel.


Oral sitafloxacin vs intravenous ceftriaxone followed by oral cefdinir for acute pyelonephritis and complicated urinary tract infection: a randomized controlled trial.
The conventional antibiotic regimen for community-acquired upper urinary tract infections with moderate severity in Thailand is parenteral ceftriaxone (CTRX) for several days followed by oral cephalosporin for 7-14 days. The aim of this study was to compare the efficacy and safety of oral sitafloxacin (STFX) with that of intravenous CTRX followed by oral cefdinir (CFDN) for the therapy of acute pyelonephritis (APN) and complicated urinary tract infection (cUTI). This open-label, randomized, controlled, noninferiority clinical trial included patients from nine centers across Thailand. Adult patients with APN or cUTI were randomly assigned to receive 100 mg of oral STFX twice daily for 7-14 days, or 2 g of intravenous CTRX for several days followed by 100 mg of oral CFDN three times per day for another 4-12 days. A total of 289 adult patients with APN or cUTI (141 in the STFX group and 148 in the CTRX/CFDN group) were included in the intent-to-treat (ITT) analysis, and 211 patients (108 in the STFX group and 103 in the CTRX/CFDN group) were included in the per-protocol (PP) analysis. The baseline characteristics of patients in both groups were comparable. The causative pathogen in most patients with APN or cUTI was Escherichia coli. The clinical success rates at the end of treatment revealed the STFX regimen to be noninferior to the CTRX/CFDN regimen (86.6% vs 83.8% for ITT analysis and 97.2% vs 99.0% for PP analysis, respectively). Adverse events with mild-to-moderate severity were similar between groups. Oral STFX is noninferior to intravenous CTRX followed by oral CFDN in adult patients with APN and cUTI. Lower rates of resistance compared to CTRX and/or CFDN and oral administration suggest STFX as a more attractive treatment option in this patient population.


Multimodality imaging of attenuated plaque using grayscale and virtual histology intravascular ultrasound and optical coherent tomography.
Although attenuated plaque is a marker for plaque vulnerability, the quantification and its implication have not been known. Multimodality pre-procedural imaging using grayscale intravascular ultrasound (IVUS), virtual histology-IVUS (VH-IVUS), and optical coherence tomography (OCT) were performed in 115 coronary lesions with diameter stenosis (DS) >30% and plaque burden ≥50% and compared the diagnostic accuracies for detecting thin-cap fibroatheromas (TCFA). A maximal arc of attenuation (40 MHz IVUS) ≥29.0° was the cutoff for predicting VH-TCFA (sensitivity 74%, specificity 66%); and OCT-TCFA (sensitivity 89%, specificity 64%), while a maximal arc attenuation ≥29.0° (20MHz IVUS) showed a poor sensitivity for predicting TCFA. Compared to the lesions with an arc of attenuation <30° as a rough cutoff value, the lesions with a maximum arc of attenuation ≥30° (40 MHz) were associated with more severe (smaller angiographic minimum lumen diameter and greater DS, smaller IVUS-MLA and a larger plaque burden) and had more unstable lesion characteristics: (1) larger remodeling index and more plaque ruptures (grayscale IVUS); (2) greater %necrotic core and more VH-TCFAs (VH-IVUS); and (3) more lipid, macrophages, cholesterol crystals, and microchannels; thinner fibrous caps; and more OCT-TCFAs, OCT-detected plaque ruptures, and red and white thrombi (OCT). Among 58 patients treated with stent implantation, postintervention peak CK-MB was higher in patients with the maximal attenuation ≥30° compared to those without (median 2.7 ng/ml [IQR 0.9-18.7 ng/ml] vs. median 0.9 ng/ml [IQR 0.7-2.1 ng/ml], P = 0.012). Attenuated plaque with a maximal attenuation ≥30° vs. <30° (40 MHz, but not 20 MHz IVUS) were more likely to be associated with unstable lesion morphology that may contribute to the immediate poststenting CK-MB elevation. © 2016 Wiley Periodicals, Inc.


Hormonal factors in reduced postprandial heat production of exercise-trained subjects.
The influence of exercise training on postprandial heat production was investigated in human subjects. Whereas resting metabolic rate was comparable for trained and nontrained subjects, the heat increment of feeding (HIF) after subjects consumed a meal containing 755 kcal was approximately 50% smaller in the trained subjects. Measurements of respiratory quotient also indicated a reduction of about 50% in glucose oxidation associated with exercise training. The levels of plasma norepinephrine increased significantly (P less than 0.01) from 200 to 300 pg/ml in the sedentary subjects, but the changes observed in trained subjects were not significant. During the early phase of the meal, plasma levels of insulin were increased, even before nutrients appeared in the blood. Throughout the study the enhanced sensitivity to insulin of the trained subjects was confirmed. the postprandial heat production was diminished in exercise-trained subjects, and it is suggested that this could be related to a reduced activity of the sympathetic nervous system. Another possibility is that this reduction in HIF is related to a facilitation of glucose disposal in the form of glycogen rather than in the form of lipids.


Immunodiagnosis of parasitic diseases with synthetic peptides.
Parasitic diseases remain as a major public health problem worldwide, not only based on their historically high morbidity and mortality rates, but also because risk factors associated with their transmission are increasing. Laboratory diagnosis and particularly immunodiagnosis is a basic tool for the demonstration, clinical management and control of these infections. Classically, the serological tests for the detection of antibodies or antigens are based on the use of crude and purified antigens. Synthetic peptides have opened a new field and perspectives, as the source of pure epitopes and molecules for diagnosis of malaria, Chagas' disease, leishmaniasis, schistosomiasis, hidatidosis, cysticercosis and fasciolosis based on the detection of antibodies and circulating antigens. Herein, are critically reviewed the relevant advances and applications of the synthetic peptides on immunodiagnosis of parasitic diseases. A variety of sequences, constructs (monomers, polymers, MAPs), immunological methods and samples have been used, demonstrating their diagnostic potential. However, in most parasitic infections it is necessary to use more than a single peptide in order to avoid the genetic restriction against certain epitopes, as well as to test them in well characteized groups of patients, in order to confirm their sensitivity and specificity. The concept of multidiagnosis with synthetic peptides, using a novel multi-dot blot assay is introduced. Finally, the chemical imitation of antigens, offers a tremendous posibilities in the diagnosis of parasitic infections in developing countries since this strategy is cheaper, simpler, reproducible, useful for large scale testing and in most cases, specific and sensitive.


Observing Electrochemical Dealloying by Single-Nanoparticle Collision.
We report direct observation of electrochemical and thermal dealloying processes of individual metal alloy nanoparticles (NPs). Electrochemical dealloying of single Ag-Hg alloy NPs was achieved in a basic solution (e.g., pH 13) by oxidizing Hg under controlled potentials. Ag can also be oxidized during single-particle collision. However, it requires elevated potentials. The strong basic environment promoted the formation of metal oxides during collision leading to a unique core-shell type nanostructure which was further confirmed by transmission electron microscopy (TEM). In thermal dealloying, Hg was evaporated due to the use of a high-energy electron beam and the process was imaged in situ inside a TEM. Both electrochemical and thermal dealloying processes resulted in the transformation of an amorphous NP to a more stable Ag-Hg alloy nanocrystal. This work demonstrates that NP collision can be a useful tool to study dealloying processes of various nanomaterials at a single-particle level.


Perceived Psychological, Economic, and Social Impact of Khat Chewing among Adolescents and Adults in Nekemte Town, East Welega Zone, West Ethiopia.
The main aim of this study was to assess psychological, economic, and social impact of khat chewing among adolescents, in Nekemte town, East Welega Zone. A community based cross-sectional study was conducted from March to June 2016 using both quantitative and qualitative methods of data collection. A total of 359 samples were included in the study. A pretested, interviewer based structured questionnaire was employed during data collection. The study found the current prevalence of khat chewing practices was 48.6%. Perceived psychological problems especially depression and anxiety were associated with khat chewing practices. The risk of depression was about 25 times higher among khat chewers compared to nonchewers. Similarly the risk of anxiety among khat chewers was about 5 times higher compared to nonchewers. Generally current khat chewing practices in the study area are relatively high. The occurrence of reported, perceived psychological problems mainly depression and anxiety was significantly higher among khat chewers compared to nonchewers. Thus efforts like creating awareness about negative effect, making different recreation methods available, and formulating common conventions regarding khat use mainly by young generations are necessary to decrease the magnitude of chewing practices and thereby its associated consequences.


Excessive Activation of TGFβ by Spinal Instability Causes Vertebral Endplate Sclerosis.
Narrowed intervertebral disc (IVD) space is a characteristic of IVD degeneration. EP sclerosis is associated with IVD, however the pathogenesis of EP hypertrophy is poorly understood. Here, we employed two spine instability mouse models to investigate temporal and spatial EP changes associated with IVD volume, considering them as a functional unit. We found that aberrant mechanical loading leads to accelerated ossification and hypertrophy of EP, decreased IVD volume and increased activation of TGFβ. Overexpression of active TGFβ in CED mice showed a similar phenotype of spine instability model. Administration of TGFβ Receptor I inhibitor attenuates pathologic changes of EP and prevents IVD narrowing. The aberrant activation of TGFβ resulting in EPs hypertrophy-induced IVD space narrowing provides a pharmacologic target that could have therapeutic potential to delay DDD.


Chromosome-level reference genomes of two imperiled desert fishes: spikedace (Meda fulgida) and loach minnow (Tiaroga cobitis).
North American minnows (Cypriniformes: Leuciscidae) comprise a diverse taxonomic group, but many members, particularly those inhabiting deserts, face elevated extinction risks. Despite conservation concerns, leuciscids remain under sampled for reference assemblies relative to other groups of freshwater fishes. Here, we present 2 chromosome-scale reference genome assemblies spikedace (Meda fulgida) and loach minnow (Tiaroga cobitis) using PacBio, Illumina and Omni-C technologies. The complete assembly for spikedace was 882.1 Mb in total length comprised of 83 scaffolds with N50 = 34.8 Mb, L50 = 11, N75 = 32.3 Mb, and L75 = 18. The complete assembly for loach minnow was 1.3 Gb in total length comprised of 550 scaffolds with N50 = 48.6 Mb, L50 = 13, N75 = 42.3 Mb, and L75 = 20. Completeness assessed via Benchmarking Universal Single-Copy Orthologues (BUSCO) metrics using the Actinopterygii BUSCO database showed ∼97% for spikedace and ∼98% for loach minnow of complete BUSCO proportions. Annotation revealed approximately 32.58 and 29.04% of spikedace and loach minnow total genome lengths to be comprised of protein-coding genes, respectively. Comparative genomic analyses of these endangered and co-distributed fishes revealed widespread structural variants, gene family expansions, and evidence of positive selection in both genomes.


A retroviral Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys peptide binds metal ions: spectroscopic studies and a proposed three-dimensional structure.
Retroviral gag gene-encoded core nucleic acid binding proteins contain either one or two sequences of the form Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys. Previously, one of us has proposed that these sequences form metal-binding domains in analogy with the "zinc finger" domains first observed in transcription factor IIIA. We report that an 18-amino acid peptide derived from the core nucleic acid binding protein from Rauscher murine leukemia virus binds metal ions such as Co2+ and Zn2+. The absorption spectrum of the peptide-Co2+ complex is highly suggestive of tetrahedral coordination involving three cysteinates and one histidine. Titration experiments indicate that the dissociation constant for the peptide-Co2+ complex is 1.0 microM and that Zn2+ binds more tightly than Co2+. A detailed three-dimensional structure for this domain based on conserved substructures in other crystallographically characterized metalloproteins and on a detailed analysis of the Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys sequences from retroviruses and other related sources is proposed.


Are Survey Respondents Lying about Their Support for Same-Sex Marriage? Lessons from a List Experiment.
Public opinion polls consistently show that a growing majority of Americans support same-sex marriage. Critics, however, raise the possibility that these polls are plagued by social desirability bias, and thereby may overstate public support for gay and lesbian rights. We test this proposition using a list experiment embedded in the 2013 Cooperative Congressional Election Study. List experiments afford respondents an anonymity that allows them to provide more truthful answers to potentially sensitive survey items. Our experiment finds no evidence that social desirability is affecting overall survey results. If there is social desirability in polling on same-sex marriage, it pushes in both directions. Indeed, our efforts provide new evidence that a national opinion majority favors same-sex marriage. To evaluate the robustness of our findings, we analyze a second list experiment, this one focusing on the inclusion of sexual orientation in employment nondiscrimination laws. Again, we find no overall evidence of bias.


Identification of a domain of the baculovirus Autographa californica multiple nucleopolyhedrovirus single-strand DNA-binding protein LEF-3 essential for viral DNA replication.
Autographa californica multiple nucleopolyhedrovirus (AcMNPV) lef-3 is one of nine genes required for viral DNA replication in transient assays. LEF-3 is predicted to contain several domains related to its functions, including nuclear localization, single-strand DNA binding, oligomerization, interaction with P143 helicase, and interaction with a viral alkaline nuclease. To investigate the essential nature of LEF-3 and the roles it may play during baculovirus DNA replication, a lef-3 null bacmid (bKO-lef3) was constructed in Escherichia coli and characterized in Sf21 cells. The results showed that AcMNPV lef-3 is essential for DNA replication, budded virus production, and late gene expression in vivo. Cells transfected with the lef-3 knockout bacmid produced low levels of early proteins (P143, DNA polymerase, and early GP64) and no late proteins (P47, VP39, or late GP64). To investigate the functional role of domains within the LEF-3 open reading frame in the presence of the whole viral genome, plasmids expressing various LEF-3 truncations were transfected into Sf21 cells together with bKO-lef3 DNA. The results showed that expression of AcMNPV LEF-3 amino acids 1 to 125 was sufficient to stimulate viral DNA replication and to support late gene expression. Expression of Choristoneura fumiferana MNPV lef-3 did not rescue any LEF-3 functions. The construction of a LEF-3 amino acid 1 to 125 rescue bacmid revealed that this region of LEF-3, when expressed in the presence of the rest of the viral genome, stimulated viral DNA replication and late and very late protein expression, as well as budded virus production.


Regulation of neuronal differentiation at the neurogenic wavefront.
Signaling mediated by the Delta/Notch system controls the process of lateral inhibition, known to regulate neurogenesis in metazoans. Lateral inhibition takes place in equivalence groups formed by cells having equal capacity to differentiate, and it results in the singling out of precursors, which subsequently become neurons. During normal development, areas of active neurogenesis spread through non-neurogenic regions in response to specific morphogens, giving rise to neurogenic wavefronts. Close contact of these wavefronts with non-neurogenic cells is expected to affect lateral inhibition. Therefore, a mechanism should exist in these regions to prevent disturbances of the lateral inhibitory process. Focusing on the developing chick retina, we show that Dll1 is widely expressed by non-neurogenic precursors located at the periphery of this tissue, a region lacking Notch1, lFng, and differentiation-related gene expression. We investigated the role of this Dll1 expression through mathematical modeling. Our analysis predicts that the absence of Dll1 ahead of the neurogenic wavefront results in reduced robustness of the lateral inhibition process, often linked to enhanced neurogenesis and the presence of morphological alterations of the wavefront itself. These predictions are consistent with previous observations in the retina of mice in which Dll1 is conditionally mutated. The predictive capacity of our mathematical model was confirmed further by mimicking published results on the perturbation of morphogenetic furrow progression in the eye imaginal disc of Drosophila. Altogether, we propose that Notch-independent Delta expression ahead of the neurogenic wavefront is required to avoid perturbations in lateral inhibition and wavefront progression, thus optimizing the neurogenic process.


Music genetics research: Association with musicality of a polymorphism in the AVPR1A gene.
Musicality is defined as a natural tendency, sensibility, knowledge, or talent to create, perceive, and play music. Musical abilities involve a great range of social and cognitive behaviors, which are influenced by both environmental and genetic factors. Although a number of studies have yielded insights into music genetics research, genes and biological pathways related to these traits are not fully understood. Our hypothesis in the current study is that genes associated with different behaviors could also influence the musical phenotype. Our aim was to investigate whether polymorphisms in six genes (AVPR1A, SLC6A4, ITGB3, COMT, DRD2 and DRD4) related to social and cognitive traits are associated with musicality in a sample of children. Musicality was assessed through an individualized music therapy assessment profile (IMTAP) which has been validated in Brazil to measure musical ability. We show here that the RS1 microsatellite of the AVPR1A gene is nominally associated with musicality, corroborating previous results linking AVPR1A with musical activity. This study is one of the first to investigate musicality in a comprehensive way, and it contributes to better understand the genetic basis underlying musical ability.


Evaluating the concordance between sequencing, imputation and microarray genotype calls in the GAW18 data.
Genotype errors are well known to increase type I errors and/or decrease power in related tests of genotype-phenotype association, depending on whether the genotype error mechanism is associated with the phenotype. These relationships hold for both single and multimarker tests of genotype-phenotype association. To assess the potential for genotype errors in Genetic Analysis Workshop 18 (GAW18) data, where no gold standard genotype calls are available, we explored concordance rates between sequencing, imputation, and microarray genotype calls. Our analysis shows that missing data rates for sequenced individuals are high and that there is a modest amount of called genotype discordance between the 2 platforms, with discordance most common for lower minor allele frequency (MAF) single-nucleotide polymorphisms (SNPs). Some evidence for discordance rates that were different between phenotypes was observed, and we identified a number of cases where different technologies identified different bases at the variant site. Type I errors and power loss is possible as a result of missing genotypes and errors in called genotypes in downstream analysis of GAW18 data.


[The Epidemiologic Observatory and the Epidemiology Service: the Campania Region experience].
As an effect of recent Laws, epidemiology will be more and more involved in the assessment of goals in Public Health and policy making, so that the debate about structure and placing of epidemiological function is more than ever actual. In this view, the route of epidemiology in Campania Region is explained, with a detailed description of the history and laws as well as of the structure and functions of both central and local units in charge of epidemiological function; weaknesses and strengths of the current system are fully examined and an hypothesis for an organizational model in the next future is formulated.


Patient and operational factors affecting wait times in a bariatric surgery program in Toronto: a retrospective cohort study.
Increasing rates of obesity have led to growing demand for bariatric surgery. This has implications for wait times, particularly in publicly funded programs. This study examined the impact of patient and operational factors on wait times in a multidisciplinary bariatric surgery program. A retrospective study was conducted involving patients who were referred to a tertiary care centre (University Health Network, Toronto Western Hospital, Toronto) for bariatric surgery between June 2008 and July 2011. Patient characteristics, dates of clinical assessments and records describing operational changes were collected. Univariable analysis and multivariable log-linear and parametric time-to-event regressions were performed to determine whether patient and operational covariates were associated with the wait time for bariatric surgery (i.e., length of preoperative evaluation). Of the 1664 patients included in the analysis, 724 underwent surgery with a mean wait time of 440 (standard deviation 198) days and a median wait time of 445 (interquartile range 298-533) days. Wait times ranged from 3 months to 4 years. Univariable and multivariable analyses showed that patients with active substance use (β = 0.3482, p = 0.02) and individuals who entered the program in more recent operational periods (β = 0.2028, p < 0.001) had longer wait times. Additionally, the median time-to-surgery increased over 3 discrete operational periods (characterized by specific program changes related to scheduling and staffing levels, and varying referral rates and defined surgical targets; p < 0.001). Some patients could be identified at referral as being at risk for longer wait times. We also found that previous operational decisions significantly increased the wait time in the program since its inception. Therefore, careful consideration must be devoted to process-level decision-making for multistage bariatric surgical programs, because managerial and procedural changes can affect timely access to treatment.


Evanescent-wave mirror for ultracold diatomic polar molecules.
We describe the interaction of an ultracold diatomic polar molecule with an evanescent-wave mirror. Several features of this system are explored, such as the coupling between internal rovibrational states of the molecule and the laser field. Numerical simulations show quantum reflection and state selection under attainable physical conditions. Such molecular optics components will facilitate the manipulation and trapping of ultracold molecules, and might serve in future applications in several fields, e.g., as devices to filter and select a state for ultracold chemistry, to measure extremely low temperatures of molecules, or to manipulate states for quantum information processing.