Respiratory transformation of nitrous oxide (N2O) to dinitrogen by Bacteria and Archaea.
N2O is a potent greenhouse gas and stratospheric reactant that has been steadily on the rise since the beginning of industrialization. It is an obligatory inorganic metabolite of denitrifying bacteria, and some production of N2O is also found in nitrifying and methanotrophic bacteria. We focus this review on the respiratory aspect of N2O transformation catalysed by the multicopper enzyme nitrous oxide reductase (N2OR) that provides the bacterial cell with an electron sink for anaerobic growth. Two types of Cu centres discovered in N2OR were both novel structures among the Cu proteins: the mixed-valent dinuclear Cu(A) species at the electron entry site of the enzyme, and the tetranuclear Cu(Z) centre as the first catalytically active Cu-sulfur complex known. Several accessory proteins function as Cu chaperone and ABC transporter systems for the biogenesis of the catalytic centre. We describe here the paradigm of Z-type N2OR, whose characteristics have been studied in most detail in the genera Pseudomonas and Paracoccus. Sequenced bacterial genomes now provide an invaluable additional source of information. New strains harbouring nos genes and capability of N2O utilization are being uncovered. This reveals previously unknown relationships and allows pattern recognition and predictions. The core nos genes, nosZDFYL, share a common phylogeny. Most principal taxonomic lineages follow the same biochemical and genetic pattern and share the Z-type enzyme. A modified N2OR is found in Wolinella succinogenes, and circumstantial evidence also indicates for certain Archaea another type of N2OR. The current picture supports the view of evolution of N2O respiration prior to the separation of the domains Bacteria and Archaea. Lateral nos gene transfer from an epsilon-proteobacterium as donor is suggested for Magnetospirillum magnetotacticum and Dechloromonas aromatica. In a few cases, nos gene clusters are plasmid borne. Inorganic N2O metabolism is associated with a diversity of physiological traits and biochemically challenging metabolic modes or habitats, including halorespiration, diazotrophy, symbiosis, pathogenicity, psychrophily, thermophily, extreme halophily and the marine habitat down to the greatest depth. Components for N2O respiration cover topologically the periplasm and the inner and outer membranes. The Sec and Tat translocons share the task of exporting Nos components to their functional sites. Electron donation to N2OR follows pathways with modifications depending on the host organism. A short chronology of the field is also presented.


Food label usage and reported difficulty with following a gluten-free diet among individuals in the USA with coeliac disease and those with noncoeliac gluten sensitivity.
Individuals with coeliac disease (CD) and those with noncoeliac gluten sensitivity (GS) have reported difficulty following a gluten-free diet (GFD); however, few studies have explored the link between the food label, gluten-free (GF) claims and the difficulty associated with following a GFD. The present study surveyed adults with CD (n = 1,583) and adults with GS (n = 797) about their reported difficulty following a GFD, including assessing the role of food labels and GF claims, as well as other factors known to contribute to this difficulty. A two-sample t-test and chi-squared tests for equality of means or proportions were used for the descriptive data and ordinal logistic regression (OLR) was used to model associations. On average, individuals with GS reported slightly more difficulty following the GFD than did participants with CD. According to the OLR results, reading the food label often was significantly associated with less reported difficulty following a GFD, whereas consuming packaged processed foods and looking for GF claims more often were significantly associated with more reported difficulty for both respondent groups. Individuals with GS may rely more heavily on the GF claim for information about a product's gluten content. Individuals with CD, on the other hand, may be more experienced food label readers and may rely more on the ingredient list for finding GF foods. More studies are needed aiming to understand the role of the food label in facilitating consumers' ability to follow a GFD.


Effect of D-004, a lipid extract from Cuban royal palm fruit, on histological changes of prostate hyperplasia induced with testosterone in rats.
Benign prostatic hyperplasia (BPH) is the nonmalignant, uncontrolled growth of prostate gland cells and stroma leading to difficulty in urinating. Lipid extracts from Saw palmetto (Arecaceae) fruits are used to treat BPH. The Cuban royal palm (Roystonea regia) is a member of this family and D-004, a lipid extract from its fruits, prevents prostate hyperplasia (PH) induced with testosterone, as opposed to dihydrotestosterone, in rodents. This study investigated whether D-004 could prevent the histological features of testosterone-induced PH in rats. Rats were distributed into six groups (10 rats per group): A negative control group receiving subcutaneous injections of soy oil and treated with vehicle, and five groups injected subcutaneously with testosterone and treated with the vehicle (positive control), D-004 (100, 200 and 400 mg/kg) or Saw palmetto (400 mg/kg). Treatments were given orally for 14 days. At sacrifice, prostates were removed and processed for light microscopy. The histopathological findings of PH were assessed according to a score-chart protocol. D-004 200 and 400 mg/kg, but not 100 mg/kg, significantly and moderately in a dose-dependent manner prevented prostate enlargement and the testosterone-induced histological changes. Compared with positive controls, D-004 200 and 400 mg/kg inhibited prostate size increases and the histological score up to 56.1% and 60.7%, respectively, while Saw palmetto 400 mg/kg reduced such variables by 45.8% and 49.0%, respectively. The effects of D-004 400 mg/kg on the histological changes, not on prostate size, were greater (p < 0.05) than those of Saw palmetto. D-004 and Saw palmetto did not affect body weight values. In conclusion, D-004 200 and 400 mg/kg administered orally for 14 days prevented the increase of prostate size and the testosterone-induced histological changes in rats, its effects being comparable or mildly better than those of Saw palmetto. These results extend previous data showing preventive effects of D-004 on testosterone-induced prostate enlargement with in rodents, and further studies are required to explore the mechanisms underlying such effects.


Three-dimensional reconstructions come to life--interactive 3D PDF animations in functional morphology.
Digital surface mesh models based on segmented datasets have become an integral part of studies on animal anatomy and functional morphology; usually, they are published as static images, movies or as interactive PDF files. We demonstrate the use of animated 3D models embedded in PDF documents, which combine the advantages of both movie and interactivity, based on the example of preserved Trigonopterus weevils. The method is particularly suitable to simulate joints with largely deterministic movements due to precise form closure. We illustrate the function of an individual screw-and-nut type hip joint and proceed to the complex movements of the entire insect attaining a defence position. This posture is achieved by a specific cascade of movements: Head and legs interlock mutually and with specific features of thorax and the first abdominal ventrite, presumably to increase the mechanical stability of the beetle and to maintain the defence position with minimal muscle activity. The deterministic interaction of accurately fitting body parts follows a defined sequence, which resembles a piece of engineering.


Binding of semirigid nicotinic agonists to nicotinic and muscarinic receptors.
Isoarecolone methiodide (1-methyl-4-acetyl-1,2,3,6-tetrahydropyridine methiodide) was previously shown to be among the most potent agonists tested at the frog neuromuscular junction. Because nicotinic receptors from different sources vary in their selectivities, isoarecolone methiodide as well as 19 additional congeners, most of which were also previously tested at the frog neuromuscular junction, were studied in binding assays. Torpedo nobiliana was the tissue source for nicotinic receptors. Two types of experiments were conducted. The first evaluated the affinities of the agonists (including acetylcholine and carbamylcholine) for the recognition site by allowing the agonists to compete for that site with 125I-alpha-bungarotoxin. The inhibition potencies obtained correlated strongly (Spearman's correlation coefficient,-0.91) with the potency obtained at the frog neuromuscular junction. The second type of experiment evaluated the agonists for their ability to activate the receptor. The binding of [3H]perhydrohistrionicotoxin, which was employed as an indicator of the activation of the receptor, was measured in the presence of each of the agonists. Isoarecolone methiodide was the most potent of all. A few of the agonists (partial agonists) were incapable of fully enhancing this binding. For the full agonists, the concentration that produced half of the maximum binding of [3H]perhydrohistrionicotoxin was defined as the EC50. The correlation coefficient (Spearman's) for EC50 versus potency at the frog neuromuscular junction was -0.73, indicating innate differences between Torpedo and frog receptors. In addition, these compounds were tested for their affinity at muscarinic receptors from rat brain. Competition experiments were carried out using [3H]N-methylscopolamine. The affinity of isoarecolone methiodide was only about 7-fold lower than that of acetylcholine and less than 2-fold lower than that of carbamylcholine. In contrast, 1-methyl-4-acetylpiperazine methiodide was much more selective for nicotinic receptors. Its activity was similar to isoarecolone methiodide at the nicotinic receptor, but it was among the weakest compounds in its affinity for the muscarinic receptor.


Eye fluke infection and lens size reduction in fish: a quantitative analysis.
Parasites have a variety of harmful effects on their hosts, some of which may be overlapping or complementary and thus easily overlooked but which are still important for the overall severity of infection. We investigated the effect of Diplostomum sp. eye fluke infection on the size of the eye lens in a range of wild and farmed fish species and those exposed to controlled parasite infection. We found that asymmetry in intensity of infection between the right and left lens of an individual fish affected lens size such that the lens with the higher intensity of infection was smaller. Interestingly, however, this was observed only in 3 of the 10 species studied (whitefish, smelt and sea trout) although in these 3 species the effect had already became evident at low intensities of infection. Furthermore, the average lens size was significantly smaller in experimentally exposed whitefish Coregonus lavaretus with a higher intensity of infection than the controls, emphasising the sensitivity of this species to parasite-induced changes in lens size. Reduction in lens size may contribute to the deleterious effects of cataract formation by intensifying the effects of individual parasites in the lens. It may also directly affect the overall optical performance of the lens and already impair host vision at low intensities of infection.


Comparative profiling of small RNAs of pig seminal plasma and ejaculated and epididymal sperm.
The similarities and differences of small RNAs in seminal plasma, epididymal sperm and ejaculated sperm remain largely undefined. We conducted a systematic comparative analysis of small RNA profiles in pig ejaculated sperm, epididymal sperm and seminal plasma and found that the diversity distribution of small RNA species was generally similar, whereas the abundance of small RNAs is dramatically different across the three libraries; miRNAs and small RNAs derived from rRNA, tRNA, small nuclear RNA, 7SK RNA, NRON RNA and cis-regulatory RNA were enriched in the three libraries, but piRNA was absent. A large population of small RNAs from ejaculated sperm are ejaculated sperm specific, and only 8-30% of small RNAs overlapped with those of epididymal sperm or seminal plasma and a small proportion (5-18%) of small RNAs were shared in the three libraries, suggesting that, in addition to the testes, sperm RNAs may also originate from seminal plasma, epididymis as well as other resources. Most miRNAs were co-distributed but differentially expressed across the three libraries, with epididymal sperm exhibiting the highest abundance, followed by ejaculated sperm and seminal plasma. The prediction of target genes of the top 10 highly expressed miRNAs across the three libraries revealed that these miRNAs may be involved in spermatogenesis, zygote development and the interaction between the environment and animals. Our study provides the first description of the similarities and differences of small RNA profiles in ejaculated sperm, epididymal sperm and seminal plasma and indicates that sperm RNA may have origins other than the testes.


Proximate biochemical composition and caloric content calculated from elemental CHN analysis: a stoichiometric concept.
Carbohydrate, lipid, and protein compositions are stoichiometrically related to organic CHN (carbon, hydrogen, nitrogen) contents. Elemental CHN analyses of total biomass and ash, therefore, provide a basis for the calculation of proximate biochemical composition and bomb caloric value. The classical nitrogen to protein conversion factor (6.25) should be replaced by 5.8±0.13. A linear relation exists between the mass fraction of non-protein carbon and the carbohydrate and lipid content. Residual water in dry organic matter can be estimated with the additional information derived from hydrogen measurements.The stoichiometric CHN method and direct biochemical analysis agreed within 10% of ash-free dry biomass (for muscle, liver and fat tissue of silver carp; gut contents composed of detritus and algae; commercial fish food). The detrital material, however, had to be corrected for non-protein nitrogen.A linear relationship between bomb caloric value and organic carbon fractions was derived on the basis of thermodynamic and stoichiometric principles, in agreement with experimental data published for bacteria, algae, protozoa and invertebrates. The highly automatic stoichiometric CHN method for the separation of nutrient contents in biomass extends existing ecophysiological concepts for the construction of balanced carbon and nitrogen, as well as biochemical and energy budgets.


Gestational diabetes mellitus. Correlations between the phenotypic and genotypic characteristics of the mother and abnormal glucose tolerance during the first year postpartum.
We evaluated glucose tolerance during the first year postpartum in 113 women with gestational diabetes mellitus (GDM) diagnosed according to the criteria of the First International Workshop-Conference on GDM and the National Diabetes Data Group. The high incidence of abnormal postpartum glucose tolerance (38% "diabetes mellitus" plus 19% "impaired glucose tolerance") was correlated with certain of the heterogeneous characteristics of the population at the time of antepartum diagnosis. Virtually all women with antepartum fasting plasma glucose (FPG) greater than or equal to 130 mg/dl (GDM class B1) remained abnormal postpartum (21/22 [95%]), which suggests that this group may include women with preexisting glucose intolerance unrecognized before pregnancy. In the remainder, those with FPG greater than or equal to 105-129 mg/dl (GDM class A2) were more likely to be abnormal postpartum than those with FPG less than 105 mg/dl (GDM class A1). Within the A1 and A2 groups, increasing maternal age, relative insulinopenia, and hyperglycemia at 2 h during antepartum OGTT were also associated with a greater likelihood of abnormal glucose tolerance postpartum. The presence of HLA-DR3 and/or -DR4 antigens was not predictive of the status of glucose tolerance during the first year postpartum, although the increased frequency of cytoplasmic islet cell antibodies in A2 and B1 subjects was associated with a high incidence of abnormal postpartum glucoregulation. The high incidence of abnormal postpartum glucose tolerance in all GDM classes makes a compelling case for careful, early, and continuing follow-up of all women with a diagnosis of GDM.(ABSTRACT TRUNCATED AT 250 WORDS)


Reduced risk of breast cancer associated with recreational physical activity varies by HER2 status.
Convincing epidemiologic evidence indicates that physical activity is inversely associated with breast cancer risk. Whether this association varies by the tumor protein expression status of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), or p53 is unclear. We evaluated the effects of recreational physical activity on risk of invasive breast cancer classified by the four biomarkers, fitting multivariable unconditional logistic regression models to data from 1195 case and 2012 control participants in the population-based Women's Contraceptive and Reproductive Experiences Study. Self-reported recreational physical activity at different life periods was measured as average annual metabolic equivalents of energy expenditure [MET]-hours per week. Our biomarker-specific analyses showed that lifetime recreational physical activity was negatively associated with the risks of ER-positive (ER+) and of HER2-negative (HER2-) subtypes (both Ptrend ≤ 0.04), but not with other subtypes (all Ptrend > 0.10). Analyses using combinations of biomarkers indicated that risk of invasive breast cancer varied only by HER2 status. Risk of HER2-breast cancer decreased with increasing number of MET-hours of recreational physical activity in each specific life period examined, although some trend tests were only marginally statistically significant (all Ptrend ≤ 0.06). The test for homogeneity of trends (HER2- vs. HER2+ ) reached statistical significance only when evaluating physical activity during the first 10 years after menarche (Phomogeneity = 0.03). Our data suggest that physical activity reduces risk of invasive breast cancers that lack HER2 overexpression, increasing our understanding of the biological mechanisms by which physical activity acts.


Prenatal and postnatal attachment: a modest correlation.
To determine whether a correlation exists between prenatal and postnatal attachment. Prospective, correlational study with data collected during the second half of pregnancy and again 1-2 months after delivery. Two hundred twenty-eight women were recruited from childbirth education classes. The women were generally young, white, well educated, married, and employed. The Prenatal Attachment Inventory (PAI) was used to measure attachment before birth. The Maternal Attachment Inventory (MAI), the How I Feel About my Baby Now Scale, and the Maternal Separation Anxiety Scale were used to measure attachment after birth. One hundred ninety-six women completed all the measures. A correlation was found between PAI and MAI scores (r = 0.41, p < 0.001). A correlation between prenatal and postnatal attachment was found. However, the modest size of the correlation indicated that other factors also influenced postnatal scores. Thus, caution should be exercised when promoting increased prenatal attachment in hopes of improving postnatal attachment.


Context-dependent activation or inhibition of Wnt-beta-catenin signaling by Kremen.
Wnt-beta-catenin signaling controls critical events in metazoan development, and its dysregulation leads to cancers and developmental disorders. Binding of a Wnt ligand to its transmembrane co-receptors Frizzled (Fz) and low-density lipoprotein (LDL) receptor-related protein (LRP) 5 or LRP6 inhibits the degradation of the transcriptional coactivator beta-catenin, which translocates to the nucleus to regulate gene expression. The secreted protein Dickkopf1 (Dkk1) inhibits Wnt signaling by binding to LRP5 and LRP6 and blocking their interaction with Wnt and Fz. Kremen 1 and 2 (Krm1 and 2, collectively termed Krms) are single-pass transmembrane Dkk1 receptors that synergize with Dkk1 to inhibit Wnt signaling by promoting the endocytosis of LRP5 and LRP6. A study now suggests that Krms, in the absence of Dkk1, potentiate Wnt signaling by maintaining LRP5 and LRP6 at the plasma membrane. It is proposed that the absence or presence of Dkk1 determines whether Krms will activate or inhibit Wnt-beta-catenin signaling, respectively. Here, we speculate that the proposed context-dependent positive and negative roles for Krms could promote biphasic Wnt signaling in response to a shallow gradient of Dkk1, resulting in the generation of precise and robust borders between cells during development. Identification of a context-dependent role for Krms in Wnt-beta-catenin signaling offers insight into the mechanism of Wnt signaling and has important developmental implications.


Identifying CNS-colonizing T cells as potential therapeutic targets to prevent progression of multiple sclerosis.
Multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS), can be suppressed in its early stages but eventually becomes clinically progressive and unresponsive to therapy. Here, we investigate whether the therapeutic resistance of progressive MS can be attributed to chronic immune cell accumulation behind the blood-brain barrier (BBB). We systematically track CNS-homing immune cells in the peripheral blood of 31 MS patients and 31 matched healthy individuals in an integrated analysis of 497,705 single-cell transcriptomes and 355,433 surface protein profiles from 71 samples. Through spatial RNA sequencing, we localize these cells in post mortem brain tissue of 6 progressive MS patients contrasted against 4 control brains (20 samples, 85,000 spot transcriptomes). We identify a specific pathogenic CD161+/lymphotoxin beta (LTB)+ T cell population that resides in brains of progressive MS patients. Intriguingly, our data suggest that the colonization of the CNS by these T cells may begin earlier in the disease course, as they can be mobilized to the blood by usage of the integrin-blocking antibody natalizumab in relapsing-remitting MS patients. As a consequence, we lay the groundwork for a therapeutic strategy to deplete CNS-homing T cells before they can fuel treatment-resistant progression. This study was supported by funding from the University Medical Center Hamburg-Eppendorf, the Stifterverband für die Deutsche Wissenschaft, the OAK Foundation, Medical Research Council UK, and Wellcome.


Carcinopodacarus polymorphus gen. n. et sp. n. from Guira guira (Cuculiformes: Cuculidae) in Brazil: a first example of male polymorphism in the family Dermationidae (Acariformes: Analgoidea).
Carcinopodacarus polymorphus gen. n. et sp. n. (Acariformes: Dermationidae: Dermationinae) is described from the guira cuckoo Guira guira (Gmelin) (Cuculiformes: Cuculidae) in Brazil. The new genus differs from the closest genus, Psittophagoides Fain, 1964, by the following features: in both sexes, the anterior spines of trochanters I and II are absent (vs present in Psittophagoides), setae d2 are distinctly developed (vs only alveoli), and genual setae mGI are absent (vs present); in males, the hysteronotal shield is split transversally at the level of trochanters III (vs hysteronotal shield entire); in females, the platelets situated posterior to the propodonotal shield are absent (vs present), the metapodosomal sclerites are present (vs absent), and the adanal shields are fused anteriorly to each other (vs separated from each other). In this species, andropolymorphism is detected for the first time for the family. It involves various characters but the most impressive feature is the structure of legs III. In hetero- and mesomorphic males, these legs are strongly hypertrophied and have a distinct ventral spur on femora III; in homeomorphic males, legs III are not modified and subequal to legs IV.


Single and multiple sevoflurane exposures during pregnancy and offspring behavior in mice.
The second trimester is a period of neurogenesis and neuronal migration, which can be affected by exposure to anesthetics. Studies also suggest that multiple exposures may have a greater impact on neurodevelopment. We investigated whether in utero single or multiple exposures to anesthetics caused long-term behavior changes. Pregnant mice were randomly divided into four groups on gestational day 14 (GD 14). Mice in the Control × 1 group were exposed to 100% oxygen for 150 min. Mice in the Sevo × 1 group were also exposed to 100% oxygen for 150 min, except that 2.5% sevoflurane was added during the first 120 min. Mice in the Control × 3 and Sevo × 3 group were identically treated as Control × 1 and Sevo × 1 group for three consecutive days, respectively (GD 14-16). Behavioral tests were performed only with the male offspring at the age of 2-4 months. Synaptic plasticity was also compared by inducing long-term potentiation in acute hippocampal slices. Single or multiple sevoflurane exposures in pregnant mice during the second trimester did not cause long-lasting behavioral consequences or changes in long-term synaptic plasticity of their offspring. Our study suggests that neither single nor multiple exposures of mice to sevoflurane during the fetal developmental period induces long-term behavioral dysfunctions or affects long-term synaptic plasticity. Additional studies focusing on early stages of neurodevelopment are necessary to confirm the effects of sevoflurane exposure during pregnancy.


The analgesic effect of oral delta-9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions.
From folk medicine and anecdotal reports it is known that Cannabis may reduce pain. In animal studies it has been shown that delta-9-tetrahydrocannabinol (THC) has antinociceptive effects or potentiates the antinociceptive effect of morphine. The aim of this study was to measure the analgesic effect of THC, morphine, and a THC-morphine combination (THC-morphine) in humans using experimental pain models. THC (20 mg), morphine (30 mg), THC-morphine (20 mg THC+30 mg morphine), or placebo were given orally and as single doses. Twelve healthy volunteers were included in the randomized, placebo-controlled, double-blinded, crossover study. The experimental pain tests (order randomized) were heat, cold, pressure, single and repeated transcutaneous electrical stimulation. Additionally, reaction time, side-effects (visual analog scales), and vital functions were monitored. For the pharmacokinetic profiling, blood samples were collected. THC did not significantly reduce pain. In the cold and heat tests it even produced hyperalgesia, which was completely neutralized by THC-morphine. A slight additive analgesic effect could be observed for THC-morphine in the electrical stimulation test. No analgesic effect resulted in the pressure and heat test, neither with THC nor THC-morphine. Psychotropic and somatic side-effects (sleepiness, euphoria, anxiety, confusion, nausea, dizziness, etc.) were common, but usually mild.


Restrictive Transfusion Strategy Is More Effective in Massive Burns: Results of the TRIBE Multicenter Prospective Randomized Trial.
Studies suggest that a restrictive transfusion strategy is safe in burns, yet the efficacy of a restrictive transfusion policy in massive burn injury is uncertain. Our objective: compare outcomes between massive burn (≥60% total body surface area (TBSA) burn) and major (20-59% TBSA) burn using a restrictive or a liberal blood transfusion strategy. Patients with burns ≥20% were block randomized by age and TBSA to a restrictive (transfuse hemoglobin <7 g/dL) or liberal (transfuse hemoglobin <10 g/dL) strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes. Three hundred and forty-five patients received 7,054 units blood, 2,886 in massive and 4,168 in restrictive. Patients were similar in age, TBSA, and inhalation injury. The restrictive group received less blood (45.57 ± 47.63 vs. 77.16 ± 55.0, p < 0.03 massive; 11.0 ± 16.70 vs. 16.78 ± 17.39, p < 0.001) major). In massive burn, the restrictive group had fewer ventilator days (p < 0.05). Median ICU days and LOS were lower in the restrictive group; wound healing, mortality, and infection did not differ. No significant outcome differences occurred in the major (20-59%) group (p > 0.05). A restrictive transfusion strategy may be beneficial in massive burns in reducing ventilator days, ICU days and blood utilization, but does not decrease infection, mortality, hospital LOS or wound healing.


Protective ventilation of preterm lambs exposed to acute chorioamnionitis does not reduce ventilation-induced lung or brain injury.
The onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response. Pregnant ewes (n = 18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n = 6), or were ventilated using an injurious high VT strategy (LPSINJ; n = 5) or a protective ventilation strategy (LPSPROT; n = 7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury. LPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in the WM, which were equivalent in magnitude between groups. Ventilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor to WM injury in infants exposed to chorioamnionitis.


Classification of Tandem Mass Spectra for Identification of N- and O-linked Glycopeptides.
Analysis of intact glycopeptides by mass spectrometry is essential to determining the microheterogeneity of protein glycosylation. Higher-energy collisional dissociation (HCD) fragmentation of glycopeptides generates mono- or disaccharide ions called oxonium ions that carry information about the structure of the fragmented glycans. Here, we investigated the link between glycan structures and the intensity of oxonium ions in the spectra of glycopeptides and utilized this information to improve the identification of glycopeptides in biological samples. Tandem spectra of glycopeptides from fetuin, glycophorin A, ovalbumin and gp120 tryptic digests were used to build a spectral database of N- and O-linked glycopeptides. Logistic regression was applied to this database to develop model to distinguish between the spectra of N- and O-linked glycopeptides. Remarkably, the developed model was found to reliably distinguish between the N- and O-linked glycopeptides using the spectral features of the oxonium ions using verification spectral set. Finally, the performance of the developed predictive model was evaluated in HILIC enriched glycopeptides extracted from human serum. The results showed that pre-classification of tandem spectra based on their glycosylation type improved the identification of N-linked glycopeptides. The developed model facilitates interpretation of tandem mass spectrometry data for assignment of glycopeptides.


Does International Travel Frequency Affect COVID-19 Biosecurity Behavior in the United States?
High-quality biosecurity practices are critical to restarting international tourism. Effective market segmentation improves the communication and efficacy of health advice. Travel frequency is an important basis for health-related consumer segmentation, as it is closely related to risk of greater exposure to infectious diseases. Theoretically grounded studies of tourist biosecurity behavior and travel frequency have largely been neglected, although insights into practices and attitudes are especially relevant for coronavirus disease of 2019 (COVID-19 (coronavirus disease of 2019) health responses. Therefore, this research constructed and tested a conceptual model applying Value-Attitude-Behavior theory to US travelers to see whether the frequency of international travel affected tourist COVID-19 related biosecurity behavior. US respondents were drawn from a panel using a quota sampling technique according to the age and gender of American outbound tourists. An online survey was administered in September 2020. The responses (n = 395) of those who traveled internationally within five years were analyzed utilizing partial least squares-structural equation modeling (PLS-SEM) with multi-group analysis. Travel frequency significantly affects biosecurity behavior. High travel frequency (≥8 trips) has the strongest effect of value on biosecurity attitudes, personal norms, social norms, and biosecurity social norms, leading to biosecurity behaviors. Biosecurity behaviors pertaining to medium travel frequency (4-7 trips) are significantly influenced by personal norms. At low travel frequency (1-3 trips) levels, biosecurity behaviors are stimulated by biosecurity attitudes and social norms, showing the highest predictive power among the three groups. This work provides insights into international travel consumer biosecurity practices and behavior. From a market segmentation perspective, the levels of international travel frequency have various influences on biosecurity values, attitudes, personal norms, social norms, and behaviors. The biosecurity behaviors of low-frequency travelers are found to be the most significant of the three groups, suggesting that individuals who travel less frequently are more likely to practice responsible COVID-19 biosecurity behavior.


Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues.
The spectrin-based membrane skeleton of the humble mammalian erythrocyte has provided biologists with a set of interacting proteins with diverse roles in organization and survival of cells in metazoan organisms. This review deals with the molecular physiology of spectrin, ankyrin, which links spectrin to the anion exchanger, and two spectrin-associated proteins that promote spectrin interactions with actin: adducin and protein 4.1. The lack of essential functions for these proteins in generic cells grown in culture and the absence of their genes in the yeast genome have, until recently, limited advances in understanding their roles outside of erythrocytes. However, completion of the genomes of simple metazoans and application of homologous recombination in mice now are providing the first glimpses of the full scope of physiological roles for spectrin, ankyrin, and their associated proteins. These functions now include targeting of ion channels and cell adhesion molecules to specialized compartments within the plasma membrane and endoplasmic reticulum of striated muscle and the nervous system, mechanical stabilization at the tissue level based on transcellular protein assemblies, participation in epithelial morphogenesis, and orientation of mitotic spindles in asymmetric cell divisions. These studies, in addition to stretching the erythrocyte paradigm beyond recognition, also are revealing novel cellular pathways essential for metazoan life. Examples are ankyrin-dependent targeting of proteins to excitable membrane domains in the plasma membrane and the Ca(2+) homeostasis compartment of the endoplasmic reticulum. Exciting questions for the future relate to the molecular basis for these pathways and their roles in a clinical context, either as the basis for disease or more positively as therapeutic targets.


Precautionary regulation in Europe and the United States: a quantitative comparison.
Much attention has been addressed to the question of whether Europe or the United States adopts a more precautionary stance to the regulation of potential environmental, health, and safety risks. Some commentators suggest that Europe is more risk-averse and precautionary, whereas the United States is seen as more risk-taking and optimistic about the prospects for new technology. Others suggest that the United States is more precautionary because its regulatory process is more legalistic and adversarial, while Europe is more lax and corporatist in its regulations. The flip-flop hypothesis claims that the United States was more precautionary than Europe in the 1970s and early 1980s, and that Europe has become more precautionary since then. We examine the levels and trends in regulation of environmental, health, and safety risks since 1970. Unlike previous research, which has studied only a small set of prominent cases selected nonrandomly, we develop a comprehensive list of almost 3,000 risks and code the relative stringency of regulation in Europe and the United States for each of 100 risks randomly selected from that list for each year from 1970 through 2004. Our results suggest that: (a) averaging over risks, there is no significant difference in relative precaution over the period, (b) weakly consistent with the flip-flop hypothesis, there is some evidence of a modest shift toward greater relative precaution of European regulation since about 1990, although (c) there is a diversity of trends across risks, of which the most common is no change in relative precaution (including cases where Europe and the United States are equally precautionary and where Europe or the United States has been consistently more precautionary). The overall finding is of a mixed and diverse pattern of relative transatlantic precaution over the period.


Perception of phrase structure in music.
Neither music nor spoken language form uniform auditory streams, rather, they are structured into phrases. For the perception of such structures, the detection of phrase boundaries is crucial. We discovered electroencephalography (EEG) and magnetoencephalography (MEG) correlates for the perception of phrase boundaries in music. In EEG, this process was marked by a positive wave approximately between 500 and 600 ms after the offset of a phrase boundary with a centroparietal maximum. In MEG, we found major activity in an even broader time window (400-700 ms). Source localization revealed that likely candidates for the generation of the observed effects are structures in the limbic system, including anterior and posterior cingulate as well as posterior mediotemporal cortex. The timing and topography of the EEG effect bear some resemblance to a positive shift (closure positive shift, CPS) found for prosodic phrase boundaries during speech perception in an earlier study, suggesting that the underlying processes might be related. Because the brain structures, which possibly underlie the observed effects, are known to be involved in memory and attention processes, we suggest that the CPS may not reflect the detection of the phrase boundary as such, but those memory and attention related processes that are necessary to guide the attention focus from one phrase to the next, thereby closing the former and opening up the next phrase.


Iatrogenic Bladder Injury: National Analysis of 30-Day Outcomes.
To examine the risk factors and outcomes of BI, a rare complication of abdominopelvic surgery. We queried the National Surgical Quality Improvement Program database to identify intraoperative bladder injury (BI) defined by the Current Procedural Terminology code for cystorrhaphy from 2005 to 2013. Propensity-score matching balanced the differences between patients with BI and the controls. The factors matched included age, body mass index, race, modified frailty index, and procedure category. There were 1685 cases of BI in 1,541,736 surgeries (0.11%). Although 49.5% of surgeries were performed in an open fashion, this approach accounted for 69.3% of BI (P < .001). Prior to matching, mortality rates and morbidity were increased for the BI group (P < .001). Moreover, age, recent chemotherapy or radiation or steroid history, and smoking were among the risk factors for BI (all P < .05). Resident involvement increased the odds of BI and complications after BI, but decreased the risk of readmission (all P < .05). After matching, 30-day mortality was no longer increased for patients with BI (P < .001). Patients with BI requiring repair did have increased median length of stay (6 days [interquartile range {IQR}: 3-11] vs 5 [IQR: 2-9]; P < .001) and operative time (203 min [IQR: 140-278] vs 134 [IQR: 86-199]; P < .001). BI patients were more likely to undergo reoperation (7.7% vs 5.3%; P = .005). Urine infection, sepsis, and bleeding were more likely in the BI group compared with the matched controls (all P < .001). Delayed repair was rare. We present the largest national series assessing iatrogenic BI and subsequent repair. BI increases 30-day complications, reoperation, and length of stay but does not increase 30-day mortality compared with matched controls. More complex surgical cases and increased baseline comorbidity were risk factors for BI.


Key success factors behind electronic medical record adoption in Thailand.
Purpose The purpose of this paper is to investigate the elements that health care personnel in Thailand believe are necessary for successful adoption of electronic medical record (EMR) systems. Design/methodology/approach Initial qualitative in-depth interviews with physicians to adapt key elements from the literature to the Thai context. The 12 elements identified included things related to managing the implementation and to IT expertise. The nationwide survey was supported by the Ministry of Public Health and returned 1,069 usable questionnaires (response rate 42 percent) from a range of medical personnel. Findings The key elements clearly separated into a managerial dimension and an IT dimension. All were considered fairly important, but managerial expertise was more critical. In particular, there should be clear EMR project goals and scope, adequate budget allocation, clinical staff must be involved in implementation, and the IT should facilitate good electronic communication. Research limitations/implications Thailand is representative of middle-income developing countries, but there is no guarantee findings can be generalized. National policies differ, as do economic structures of health care industries. The focus is on management at the organizational level, but future research must also examine macro-level issues, as well as gain more depth into thinking of individual health care personnel. Practical implications Technical issues of EMR implementation are certainly important. However, it is clear actual adoption and use of the system also depends very heavily on managerial issues. Originality/value Most research on EMR implementation has been in developed countries, and has often focussed more on technical issues rather than examining managerial issues closely. Health IT is also critical in developing economies, and management of health IT implementation must be well understood.


Central Australian Ocular Health Study: design and baseline description of participants.
To describe the design and demographic characteristics of a study to determine the prevalence of ocular morbidity among indigenous Australians living within remote central Australia. 1884 individuals aged 20 years or older, living in one of 30 remote communities within the statistical local area of 'central Australia' were recruited for this study. Participants were recruited as they presented to the eye clinic at each remote community. Patients underwent visual acuity testing and subjective refraction. Following this they had a comprehensive ocular assessment. A baseline description of the participants is presented. 1884 participants were recruited including 689 (36.6%) males and 1195 (63.4%) females. This equates to 36% of those aged 20 years or older and 67% of those aged 40 years or older living in central Australia. 55% of participants were diabetic and 20% of participants were symptomatic of an eye condition, but the majority of these only had presbyopia. Combined, those who presented due to diabetes (regardless of symptoms), due to presbyopia, or without any symptoms made up 95% of the sample. Despite being recruited through clinics, the majority of participants presented for a 'check-up' because the clinic was available and not due to symptoms. Therefore, the data we collected may be used to establish the current prevalence of ocular morbidity within the indigenous community living in remote central Australia with particular reference to those aged 40 years or older. As such, this can help to determine the current and future needs of this population.


Continuous-wave photothermal deflection spectroscopy with fundamental and harmonic responses.
A diffraction theory of continuous-wave photothermal deflection (PD) spectroscopy with fundamental and harmonic responses is presented. The displacement of the probe beam centroid is found to be a rigorous measurement of PD effect, which leads to a set of analytical solutions to the fundamental and the second-order harmonics. Harmonics are caused by the diffraction of the probe beam in the mirage region, which could not be handled by geometric-optics theory. This theory can be used to study bulk materials, thin films, and layered-structure samples. Experimental results are in good agreement with the theory.


Machismo, Marianismo, and Negative Cognitive-Emotional Factors: Findings From the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study.
There is limited research on the traditional Hispanic male and female gender roles of machismo and marianismo, respectively, in relation to negative cognitions and emotions. Given the vulnerability of Hispanics to negative cognitions and emotions, it is important to examine sociocultural correlates of emotional distress. Therefore, we examined associations of machismo and marianismo with negative cognitive-emotional factors (i.e., depression symptoms; cynical hostility; and trait anxiety and anger) in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study, a cross-sectional cohort study of sociocultural and psychosocial correlates of cardiometabolic health. Participants were aged 18-74 years and self-identified as Hispanic of Central American, Cuban, Dominican, Mexican, Puerto Rican, South American, and other Hispanic background (N = 4,426). Results revealed that specific components of machismo (traditional machismo) and marianismo (family and spiritual pillar dimensions) were associated with higher levels of negative cognitions and emotions after adjusting for socio-demographic factors (p < .05); these associations remained consistent across sex, Hispanic background group, and acculturation. Findings can inform mental health interventions and contribute to our understanding of the importance of gender role socialization in the context of self-reported negative cognitive-emotional factors in Hispanics.


Control of lipid oxidation during exercise: role of energy state and mitochondrial factors.
Despite considerable progress during recent years our understanding of how lipid oxidation (LOx) is controlled during exercise remains incomplete. This review focuses on the role of mitochondria and energy state in the control of LOx. LOx increases in parallel with increased energy demand up to an exercise intensity of about 50-60% of VO(2max) after which the contribution of lipid decreases. The switch from lipid to carbohydrate (CHO) is of energetic advantage due to the increased ATP/O(2) yield. In the low-intensity domain (<50%VO(2max)) a moderate reduction in energy state will stimulate both LOx and CHO oxidation and relative fuel utilization is mainly controlled by substrate availability and the capacity of the metabolic pathways. In the high-intensity domain (>60%VO(2max)) there is a pronounced decrease in energy state, which will stimulate glycolysis in excess of the substrate requirements of the oxidative processes. This will lead to acidosis, reduced levels of free Coenzyme A (CoASH) and reduced levels of free carnitine. Acidosis and reduced carnitine may limit the carnitine-mediated transfer of long-chain fatty acids (LCFA) into mitochondria and may thus explain the observed reduction in LOx during high-intensity exercise. Another potential mechanism, suggested in this review, is that Acyl-CoA synthetase (ACS), an initial step in LCFA catabolism, functions as a regulator of LOx. ACS activity is suggested to be under control of CoASH and energy state. Furthermore, evidence exists that additional control points exist beyond mitochondrial FA influx. The nature and site of this control remain to be investigated.


γ-Glutamylcysteine synthetase (γ-GCS) as a target for overcoming chemo- and radio-resistance of human hepatocellular carcinoma cells.
This study uncovered that the genetically endowed intracellular glutathione contents (iGSH) regulated by the catalytic subunit of γ‑glutamylcysteine synthetase heavy chain (γ‑GCSh) as a prime target for overcoming both the inherited and stimuli-activated chemo- and radio-resistance of hepatocellular carcinoma (HCC) cells. Reactive oxygen species (ROS) production and mitochondrial membrane potential (Δψm) were determined by the probe-based flow cytometry. The TUNEL assay was used as an index of radio-sensitivity and the MTT assay was used as an index of chemo-sensitivity against various anti-cancer agents. iGSH and γ‑GCSh activity were measured by HPLC methods. γ‑GCSh-overexpressing GCS30 cell line was established by tetracycline-controlled Tet-OFF gene expression system in SK-Hep-1 cells. The relative radio-sensitivities of a panel of five HCC cells were found to be correlated negatively with both the contents of iGSH and their corresponding γ‑GCSh activities with an order of abundance being Hep G2 > Hep 3B > J5 > Mahlavu > SK-Hep-1, respectively. Similarly, the cytotoxicity response patterns of these HCC cells against arsenic trioxide (ATO), a ROS-producing anti-cancer drug, were exactly identical to the order of ranking instigated by the radiotherapy (RT) treatment. Next, γ‑GCSh-overexpressing GCS30 cells were found to possess excellent ability to profoundly mitigate both the drop of Δψm and apoptotic TUNEL-positive cell population engendered by ATO, cisplatin, doxorubicin, and RT treatments. Our data unequivocally demonstrate that γ‑GCSh may represent a prime target for overcoming anti-cancer drugs and RT resistance for HCC cells.


Genetic similarities between Cyclospora cayetanensis and cecum-infecting avian Eimeria spp. in apicoplast and mitochondrial genomes.
Cyclospora cayetanensis is an important cause for diarrhea in children in developing countries and foodborne outbreaks of cyclosporiasis in industrialized nations. To improve understanding of the basic biology of Cyclospora spp. and development of molecular diagnostic tools and therapeutics, we sequenced the complete apicoplast and mitochondrial genomes of C. cayetanensis. The genome of one Chinese C. cayetanensis isolate was sequenced using Roche 454 and Illumina technologies. The assembled genomes of the apicoplast and mitochondrion were retrieved, annotated, and compared with reference genomes for other apicomplexans to infer genome organizations and phylogenetic relationships. Sequence variations in the mitochondrial genome were identified by comparison of two C. cayetanensis nucleotide sequences from this study and a recent publication. The apicoplast and mitochondrial genomes of C. cayetanensis are 34,155 and 6,229 bp in size and code for 65 and 5 genes, respectively. Comparative genomic analysis showed high similarities between C. cayetanensis and Eimeria tenella in both genomes; they have 85.6% and 90.4% nucleotide sequence similarities, respectively, and complete synteny in gene organization. Phylogenetic analysis of the genomic sequences confirmed the genetic similarities between cecum-infecting avian Eimeria spp. and C. cayetanensis. Like in other coccidia, both genomes of C. cayetanensis are transcribed bi-directionally. The apicoplast genome is circular, codes for the complete machinery for protein biosynthesis, and contains two inverted repeats that differ slightly in LSU rRNA gene sequences. In contrast, the mitochondrial genome has a linear concatemer or circular mapping topology. Eight single-nucleotide and one 7-bp multiple-nucleotide variants were detected between the mitochondrial genomes of C. cayetanensis from this and recent studies. The apicoplast and mitochondrial genomes of C. cayetanensis are highly similar to those of cecum-infecting avian Eimeria spp. in both genome organization and sequences. The availability of sequence data beyond rRNA and heat shock protein genes could facilitate studies of C. cayetanensis biology and development of genotyping tools for investigations of cyclosporiasis outbreaks.


Earliest occupation of the Central Aegean (Naxos), Greece: Implications for hominin and Homo sapiens' behavior and dispersals.
We present evidence of Middle Pleistocene activity in the central Aegean Basin at the chert extraction and reduction complex of Stelida (Naxos, Greece). Luminescence dating places ~9000 artifacts in a stratigraphic sequence from ~13 to 200 thousand years ago (ka ago). These artifacts include Mousterian products, which arguably provide first evidence for Neanderthals in the region. This dated material attests to a much earlier history of regional exploration than previously believed, opening the possibility of alternative routes into Southeast Europe from Anatolia (and Africa) for (i) hominins, potentially during sea level lowstands (e.g., Marine Isotope Stage 8) permitting terrestrial crossings across the Aegean, and (ii) Homo sapiens of the Early Upper Paleolithic (Aurignacian), conceivably by sea.


Socioeconomic and geographic disparities in health information seeking and Internet use in Puerto Rico.
Geographically isolated Hispanic populations, such as those living in Puerto Rico, may face unique barriers to health information access. However, little is known about health information access and health information-seeking behaviors of this population. To examine differences in health and cancer information seeking among survey respondents who ever used the Internet and those who did not, and to explore sociodemographic and geographic trends. Data for our analyses were from a special implementation of the Health Information National Trends Survey conducted in Puerto Rico in 2009. We collected data through random digit dialing, computer-assisted telephone interviews (N = 639). The sample was drawn from the eight geographic regions of the Puerto Rico Department of Health. To account for complex survey design and perform weighted analyses to obtain population estimates, we analyzed the data using SUDAAN. Frequencies, cross-tabulation with chi-square, and logistic regression analyses were conducted. Geographic information system maps were developed to examine geographic distributions of Internet use and information seeking. Of 639 participants, 142 (weighted percentage 32.7%) indicated that they had ever gone online to access the Internet or World Wide Web; this proportion was substantially lower than that of US mainland Hispanics who reported using the Internet (49%). While 101 of 142 (weighted percentage 59.6%) respondents who used the Web had ever sought health information, only 118 of 497 (weighted percentage 20.0%) of those who did not use the Web had sought health information. The pattern was similar for cancer information: 76 of 142 respondents (weighted percentage 47.2%) who used the Web had ever sought cancer information compared with 105 of 497 (weighted percentage 18.8%) of those who had not used the Web. These results were slightly lower but generally consistent with US mainland Hispanics' health (50.9%) and cancer (26.4%) information seeking. Results of separate logistic regression models controlling for sociodemographic characteristics demonstrated that, compared with individuals who did not seek health or cancer information, those who did were over 5 times as likely to have used the Internet (odds ratio 5.11, P < .001). Those who sought cancer information were over twice as likely to have used the Internet (odds ratio 2.5, P < .05). The frequency of Internet use and health and cancer information seeking was higher in the San Juan metro region than in more rural areas. Our results contribute to the evidence base for health and cancer communication planning for Puerto Rico, and suggest that health education and outreach efforts should explore the use of available and trusted methods of dissemination such as radio and television, as well as community-based health care providers and organizations, to supplement and encourage use of the Internet as a source of health information.


The functional human neuroanatomy of food pleasure cycles.
Food ensures our survival and is a potential source of pleasure and general well-being. In order to survive, the human brain is required to optimize the resource allocation such that rewards are pursued when relevant. This means that food intake follows a similar cyclical time course to other rewards with phases related to expectation, consummation and satiety. Here we develop a multilevel model for the full cycle of eating behavior based on the evidence for the brain networks and mechanisms initiating, sustaining and terminating the various phases of eating. We concentrate on how the underlying reward mechanisms of wanting, liking and learning lead to how human food intake is governed by both hedonic and homeostatic principles. We describe five of the main processing principles controlling food intake: hunger and attentional signal processing; motivation-independent discriminative processing; reward representations; learning-dependent multimodal sensory representations and hedonic experience. Overall, the evidence shows that while human food intake is complex, we are making progress in understanding the underlying mechanisms and that the brain networks supporting the food pleasure cycle are remarkably similar to those underlying the processing of other rewards.


Evaluation of serum biochemical marker concentrations and survival time in dogs with protein-losing enteropathy.
To evaluate serum concentrations of biochemical markers and survival time in dogs with protein-losing enteropathy (PLE). Prospective study. 29 dogs with PLE and 18 dogs with food-responsive diarrhea (FRD). Data regarding serum concentrations of various biochemical markers at the initial evaluation were available for 18 of the 29 dogs with PLE and compared with findings for dogs with FRD. Correlations between biochemical marker concentrations and survival time (interval between time of initial evaluation and death or euthanasia) for dogs with PLE were evaluated. Serum C-reactive protein concentration was high in 13 of 18 dogs with PLE and in 2 of 18 dogs with FRD. Serum concentration of canine pancreatic lipase immunoreactivity was high in 3 dogs with PLE but within the reference interval in all dogs with FRD. Serum α1-proteinase inhibitor concentration was less than the lower reference limit in 9 dogs with PLE and 1 dog with FRD. Compared with findings in dogs with FRD, values of those 3 variables in dogs with PLE were significantly different. Serum calprotectin (measured by radioimmunoassay and ELISA) and S100A12 concentrations were high but did not differ significantly between groups. Seventeen of the 29 dogs with PLE were euthanized owing to this disease; median survival time was 67 days (range, 2 to 2,551 days). Serum C-reactive protein, canine pancreatic lipase immunoreactivity, and α1-proteinase inhibitor concentrations differed significantly between dogs with PLE and FRD. Most initial biomarker concentrations were not predictive of survival time in dogs with PLE.


Gluten-related disorders: gluten ataxia.
The term gluten-related disorders (GRD) refers to a spectrum of diverse clinical manifestations triggered by the ingestion of gluten in genetically susceptible individuals. They include both intestinal and extraintestinal manifestations. Gluten ataxia (GA) is one of the commonest neurological manifestations of GRD. It was originally defined as otherwise idiopathic sporadic ataxia in the presence of circulating antigliadin antibodies of IgA and/or IgG type. Newer more specific serological markers have been identified but are not as yet readily available. GA has a prevalence of 15% amongst all ataxias and 40% of all idiopathic sporadic ataxias. It usually presents with gait and lower limb ataxia. It is of insidious onset with a mean age at onset of 53 years. Up to 40% of patients have evidence of enteropathy on duodenal biopsy. Gastrointestinal symptoms are seldom prominent and are not a reliable indicator for the presence of enteropathy. Furthermore, the presence of enteropathy does not influence the response to a gluten-free diet. Most patients will stabilise or improve with strict adherence to gluten-free diet depending on the duration of the ataxia prior to the treatment. Up to 60% of patients with GA have evidence of cerebellar atrophy on MR imaging, but all patients have spectroscopic abnormalities primarily affecting the vermis. Recent evidence suggests that patients with newly diagnosed coeliac disease presenting to the gastroenterologists have abnormal MR spectroscopy at presentation associated with clinical evidence of subtle cerebellar dysfunction. The advantage of early diagnosis and treatment (mean age 42 years in patients presenting with gastrointestinal symptoms vs. 53 years in patients presenting with ataxia) may protect the first group from the development and/or progression of neurological dysfunction.


Analysis of trabecular bone structure using Fourier transforms and neural networks.
Hip fracture due to osteoporosis (OP) and hip osteoarthritis (OA) are both important causes of locomotor morbidity in the elderly population. In osteoporosis, bone mass gradually decreases until the skeleton is too fragile to support the body and a fracture occurs, typically in the femur, wrist, or spine. In osteoarthritis, there is a proliferation of bone, leading to a stiffening of the tissue. Current clinical methods for assessment of bone changes in these disorders largely depend on assessing bone mineral density. However, this does not provide any information about bone structure which is considered to be an equally important factor in assessing bone quality. This paper presents a novel approach for computer analysis of trabecular (or cancellous) bone structure. The technique uses a Fourier transform to generate a "spectral fingerprint" of an image. Principal components analysis is then applied to identify key features from the Fourier transform and this information passed to a neural network for classification. Testing this on a series of 100 histological sections of trabecular bone from patients with OP and OA and a normal group correctly classified over 90% of the OP group with an overall accuracy of 77%-84%. Such high success rates on a small group suggest that this may provide a simple, but powerful, method for identifying alterations in bone structure.


Pten dose dictates cancer progression in the prostate.
Complete inactivation of the PTEN tumor suppressor gene is extremely common in advanced cancer, including prostate cancer (CaP). However, one PTEN allele is already lost in the vast majority of CaPs at presentation. To determine the consequence of PTEN dose variations on cancer progression, we have generated by homologous recombination a hypomorphic Pten mouse mutant series with decreasing Pten activity: Pten(hy/+) > Pten(+/-) > Pten(hy/-) (mutants in which we have rescued the embryonic lethality due to complete Pten inactivation) > Pten prostate conditional knockout (Pten(pc)) mutants. In addition, we have generated and comparatively analyzed two distinct Pten(pc) mutants in which Pten is inactivated focally or throughout the entire prostatic epithelium. We find that the extent of Pten inactivation dictate in an exquisite dose-dependent fashion CaP progression, its incidence, latency, and biology. The dose of Pten affects key downstream targets such as Akt, p27(Kip1), mTOR, and FOXO3. Our results provide conclusive genetic support for the notion that PTEN is haploinsufficient in tumor suppression and that its dose is a key determinant in cancer progression.


Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN trial.
Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy. To determine if administration of BMCs through transendocardial injections improves myocardial perfusion, reduces left ventricular end-systolic volume (LVESV), or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina. A phase 2 randomized double-blind, placebo-controlled trial of symptomatic patients (New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV) with a left ventricular ejection fraction of 45% or less, a perfusion defect by single-photon emission tomography (SPECT), and coronary artery disease not amenable to revascularization who were receiving maximal medical therapy at 5 National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) sites between April 29, 2009, and April 18, 2011. Bone marrow aspiration (isolation of BMCs using a standardized automated system performed locally) and transendocardial injection of 100 million BMCs or placebo (ratio of 2 for BMC group to 1 for placebo group). Co-primary end points assessed at 6 months: changes in LVESV assessed by echocardiography, maximal oxygen consumption, and reversibility on SPECT. Phenotypic and functional analyses of the cell product were performed by the CCTRN biorepository core laboratory. Of 153 patients who provided consent, a total of 92 (82 men; average age: 63 years) were randomized (n = 61 in BMC group and n = 31 in placebo group). Changes in LVESV index (-0.9 mL/m(2) [95% CI, -6.1 to 4.3]; P = .73), maximal oxygen consumption (1.0 [95% CI, -0.42 to 2.34]; P = .17), and reversible defect (-1.2 [95% CI, -12.50 to 10.12]; P = .84) were not statistically significant. There were no differences found in any of the secondary outcomes, including percent myocardial defect, total defect size, fixed defect size, regional wall motion, and clinical improvement. Among patients with chronic ischemic heart failure, transendocardial injection of autologous BMCs compared with placebo did not improve LVESV, maximal oxygen consumption, or reversibility on SPECT. clinicaltrials.gov Identifier: NCT00824005.


Why leaves turn red in autumn. The role of anthocyanins in senescing leaves of red-osier dogwood.
Why the leaves of many woody species accumulate anthocyanins prior to being shed has long puzzled biologists because it is unclear what effects anthocyanins may have on leaf function. Here, we provide evidence for red-osier dogwood (Cornus stolonifera) that anthocyanins form a pigment layer in the palisade mesophyll layer that decreases light capture by chloroplasts. Measurements of leaf absorbance demonstrated that red-senescing leaves absorbed more light of blue-green to orange wavelengths (495-644 nm) compared with yellow-senescing leaves. Using chlorophyll a fluorescence measurements, we observed that maximum photosystem II (PSII) photon yield of red-senescing leaves recovered from a high-light stress treatment, whereas yellow-senescing leaves failed to recover after 6 h of dark adaptation, which suggests photo-oxidative damage. Because no differences were observed in light response curves of effective PSII photon yield for red- and yellow-senescing leaves, differences between red- and yellow-senescing cannot be explained by differences in the capacities for photochemical and non-photochemical light energy dissipation. A role of anthocyanins as screening pigments was explored further by measuring the responses PSII photon yield to blue light, which is preferentially absorbed by anthocyanins, versus red light, which is poorly absorbed. We found that dark-adapted PSII photon yield of red-senescing leaves recovered rapidly following illumination with blue light. However, red light induced a similar, prolonged decrease in PSII photon yield in both red- and yellow-senescing leaves. We suggest that optical masking of chlorophyll by anthocyanins reduces risk of photo-oxidative damage to leaf cells as they senesce, which otherwise may lower the efficiency of nutrient retrieval from senescing autumn leaves.


Linking molecular biomarkers with higher level condition indicators to identify effects of copper exposures on the endangered delta smelt (Hypomesus transpacificus).
The delta smelt (Hypomesus transpacificus) is an endangered pelagic fish species endemic to the Sacramento-San Joaquin estuary (CA, USA), and considered an indicator of ecosystem health. Copper is a contaminant of concern in Californian waterways that may affect the development and survival of this endangered species. The experimental combination of molecular biomarkers with higher level effects may allow for interpretation of responses in a functional context that can be used to predict detrimental outcomes caused by exposure. A delta smelt microarray was developed and applied to screen for candidate molecular biomarkers that may be used in monitoring programs. Functional classifications of microarray responses were used along with quantitative polymerase chain reaction determining effects upon neuromuscular, digestive, and immune responses in Cu-exposed delta smelt. Differences in sensitivity were measured between juveniles and larvae (median lethal concentration = 25.2 and 80.4 µg/L Cu(2+), respectively). Swimming velocity declined with higher exposure concentrations in a dose-dependent manner (r = -0.911, p < 0.05), though was not statistically significant to controls. Genes encoding for aspartoacylase, hemopexin, α-actin, and calcium regulation proteins were significantly affected by exposure and were functionally interpreted with measured swimming responses. Effects on digestion were measured by upregulation of chitinase and downregulation of amylase, whereas downregulation of tumor necrosis factor indicated a probable compromised immune system. Results from this study, and many others, support the use of functionally characterized molecular biomarkers to assess effects of contaminants in field scenarios. We thus propose that to attribute environmental relevance to molecular biomarkers, research should concentrate on their application in field studies with the aim of assisting monitoring programs.


Hot spot dynamics in carbon nanotube array devices.
We report on the dynamics of spatial temperature distributions in aligned semiconducting carbon nanotube array devices with submicrometer channel lengths. By using high-resolution optical microscopy in combination with electrical transport measurements, we observe under steady state bias conditions the emergence of time-variable, local temperature maxima with dimensions below 300 nm, and temperatures above 400 K. On the basis of time domain cross-correlation analysis, we investigate how the intensity fluctuations of the thermal radiation patterns are correlated with the overall device current. The analysis reveals the interdependence of electrical current fluctuations and time-variable hot spot formation that limits the overall device performance and, ultimately, may cause device degradation. The findings have implications for the future development of carbon nanotube-based technologies.


Knowledge Dissemination of Intimate Partner Violence Intervention Studies Measured Using Alternative Metrics: Results From a Scoping Review.
Alternative metrics measure the number of online mentions that an academic paper receives, including mentions in social media and online news outlets. It is important to monitor and measure dispersion of intimate partner violence (IPV) victim intervention research so that we can improve our knowledge translation and exchange (KTE) processes improving utilization of study findings. The objective of this study is to describe the dissemination of published IPV victim intervention studies and to explore which study characteristics are associated with a greater number of alternative metric mentions and conventional citations. As part of a larger scoping review, we conducted a literature search to identify IPV intervention studies. Outcomes included znumber of alternative metric mentions and conventional citations. Fifty-nine studies were included in this study. The median number of alternative metric mentions was six, and the median number of conventional citations was two. Forty-one percent of the studies (24/59) had no alternative metric mentions, and 27% (16/59) had no conventional citations. Longer time since publication was significantly associated with a greater number of mentions and citations, as were systematic reviews and randomized controlled trial designs. The majority of IPV studies receive little to no online attention or citations in academic journals, indicating a need for the field to focus on implementing strong knowledge dissemination plans. The papers receiving the most alternative metric mentions and conventional citations were also the more rigorous study designs, indicating a need to focus on study quality. We recommend using alternative metrics in conjunction with conventional metrics to evaluate the full dissemination of IPV research.


Pearl millet genome sequence provides a resource to improve agronomic traits in arid environments.
Pearl millet [Cenchrus americanus (L.) Morrone] is a staple food for more than 90 million farmers in arid and semi-arid regions of sub-Saharan Africa, India and South Asia. We report the ∼1.79 Gb draft whole genome sequence of reference genotype Tift 23D2B1-P1-P5, which contains an estimated 38,579 genes. We highlight the substantial enrichment for wax biosynthesis genes, which may contribute to heat and drought tolerance in this crop. We resequenced and analyzed 994 pearl millet lines, enabling insights into population structure, genetic diversity and domestication. We use these resequencing data to establish marker trait associations for genomic selection, to define heterotic pools, and to predict hybrid performance. We believe that these resources should empower researchers and breeders to improve this important staple crop.


A systems level predictive model for global gene regulation of methanogenesis in a hydrogenotrophic methanogen.
Methanogens catalyze the critical methane-producing step (called methanogenesis) in the anaerobic decomposition of organic matter. Here, we present the first predictive model of global gene regulation of methanogenesis in a hydrogenotrophic methanogen, Methanococcus maripaludis. We generated a comprehensive list of genes (protein-coding and noncoding) for M. maripaludis through integrated analysis of the transcriptome structure and a newly constructed Peptide Atlas. The environment and gene-regulatory influence network (EGRIN) model of the strain was constructed from a compendium of transcriptome data that was collected over 58 different steady-state and time-course experiments that were performed in chemostats or batch cultures under a spectrum of environmental perturbations that modulated methanogenesis. Analyses of the EGRIN model have revealed novel components of methanogenesis that included at least three additional protein-coding genes of previously unknown function as well as one noncoding RNA. We discovered that at least five regulatory mechanisms act in a combinatorial scheme to intercoordinate key steps of methanogenesis with different processes such as motility, ATP biosynthesis, and carbon assimilation. Through a combination of genetic and environmental perturbation experiments we have validated the EGRIN-predicted role of two novel transcription factors in the regulation of phosphate-dependent repression of formate dehydrogenase-a key enzyme in the methanogenesis pathway. The EGRIN model demonstrates regulatory affiliations within methanogenesis as well as between methanogenesis and other cellular functions.


Plant odor analysis of apple: antennal response of codling moth females to apple volatiles during phenological development.
Volatile compounds were collected from apple branches (Malus domestica) at different developmental stages, and the antennal response of codling moth females (Cydia pomonella) to these compounds was recorded by electroantennography coupled to gas chromatography. Presence of a range of terpenoid compounds, many of which had antennal activity, was characteristic for volatile collections from branches with leaves, and from small green apples. Nine compounds from branches with leaves and green fruit consistently elicited an antennal response: methyl salicylate, (E)-beta-farnesene, beta-caryophyllene, 4,8-dimethyl-1,3(E),7-nonatriene, (Z)3-hexenol, (Z,E)-alpha-farnesene, linalool, germacrene D, and (E,E)-alpha-farnesene. The bouquet emitted from flowering branches contained in addition several benzenoid compounds which were not found after bloom. Small green apples, which are the main target of codling moth oviposition during the first seasonal flight period, released very few esters. In comparison, fully grown apples released a large number of esters, but fewer terpenoids. The study of apple volatiles eliciting an antennal response, together with a survey of the seasonal change in the release of these compounds, is the first step toward the identification of volatiles mediating host-finding and oviposition in codling moth females.


Genetic substructure of Kuwaiti population reveals migration history.
The State of Kuwait is characterized by settlers from Saudi Arabia, Iran, and other regions of the Arabian Peninsula. The settlements and subsequent admixtures have shaped the genetics of Kuwait. High prevalence of recessive disorders and metabolic syndromes (that increase risk of diabetes) is seen in the peninsula. Understanding the genetic structure of its population will aid studies designed to decipher the underlying causes of these disorders. In this study, we analyzed 572,366 SNP markers from 273 Kuwaiti natives genotyped using the illumina HumanOmniExpress BeadChip. Model-based clustering identified three genetic subgroups with different levels of admixture. A high level of concordance (Mantel test, p=0.0001 for 9999 repeats) was observed between the derived genetic clusters and the surname-based ancestries. Use of Human Genome Diversity Project (HGDP) data to understand admixtures in each group reveals the following: the first group (Kuwait P) is largely of West Asian ancestry, representing Persians with European admixture; the second group (Kuwait S) is predominantly of city-dwelling Saudi Arabian tribe ancestry, and the third group (Kuwait B) includes most of the tent-dwelling Bedouin surnames and is characterized by the presence of 17% African ancestry. Identity by Descent and Homozygosity analyses find Kuwait's population to be heterogeneous (placed between populations that have large amount of ROH and the ones with low ROH) with Kuwait S as highly endogamous, and Kuwait B as diverse. Population differentiation FST estimates place Kuwait P near Asian populations, Kuwait S near Negev Bedouin tribes, and Kuwait B near the Mozabite population. FST distances between the groups are in the range of 0.005 to 0.008; distances of this magnitude are known to cause false positives in disease association studies. Results of analysis for genetic features such as linkage disequilibrium decay patterns conform to Kuwait's geographical location at the nexus of Africa, Europe, and Asia.


Redressing the Corporate Cultivation of Consumption: Releasing the Weapons of the Structurally Weak.
Corporate control of the global food system has resulted in greater global availability of highly processed, packaged and very palatable unhealthy food and beverages. Environmental harm, including climate change and biodiversity loss, occurs along the supply chains associated with trans-national corporations' (TNCs') practices and products. In essence, the corporatization of the global food system has created the conditions that cultivate excess consumption, manufacture disease epidemics and harm the environment. TNCs have used their structural power - their positions in material structures and organizational networks - to establish rules, processes and norms that reinforce and extend the paradigm of the neoliberal corporate food system. As a result, policy and regulatory environments, and societal norms are favourable to TNC's interests, to the detriment of nutrition, health and environmental outcomes. There is hope, however. Power, of which there is many forms, is held not just by the TNCs but by all actors concerned about and connected to the food system. This paper aims to understand these power dynamics, and identify how structurally weak, public-interest actors can release their agency and work to achieve positive structural change. Such an analysis will help understand how the status quo can be disrupted and healthy and sustainable food systems created. The paper draws from the health governance and social movement literature, examining the Doha Declaration on the Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement and Public Health, the Framework Convention on Tobacco Control (FCTC), and the Divestment movement. These cases demonstrate the many 'weapons of the weak' that can, against all odds recalibrate structural inequities. There is no one approach to transforming the corporate food system to become a healthy and sustainable food system. It involves coalition building; articulation of an ambitious shared vision; strategic use of multi-level institutional processes; social mobilization among like-minded and unusual bedfellows, and organized campaigns; political and policy entrepreneurs, and compelling issue framing.


The safety evaluation of food flavoring substances: the role of genotoxicity studies.
The Flavor and Extract Manufacturers Association (FEMA) Expert Panel relies on the weight of evidence from all available data in the safety evaluation of flavoring substances. This process includes data from genotoxicity studies designed to assess the potential of a chemical agent to react with DNA or otherwise cause changes to DNA, either in vitro or in vivo. The Panel has reviewed a large number of in vitro and in vivo genotoxicity studies during the course of its ongoing safety evaluations of flavorings. The adherence of genotoxicity studies to standardized protocols and guidelines, the biological relevance of the results from those studies, and the human relevance of these studies are all important considerations in assessing whether the results raise specific concerns for genotoxic potential. The Panel evaluates genotoxicity studies not only for evidence of genotoxicity hazard, but also for the probability of risk to the consumer in the context of exposure from their use as flavoring substances. The majority of flavoring substances have given no indication of genotoxic potential in studies evaluated by the FEMA Expert Panel. Examples illustrating the assessment of genotoxicity data for flavoring substances and the consideration of the factors noted above are provided. The weight of evidence approach adopted by the FEMA Expert Panel leads to a rational assessment of risk associated with consumer intake of flavoring substances under the conditions of use.


Equisetum thermale sp. nov. (Equisetales) from the Jurassic San Agustín hot spring deposit, Patagonia: anatomy, paleoecology, and inferred paleoecophysiology.
Dated molecular phylogenies suggest a Cenozoic origin for the crown group of Equisetum. but compression fossil equisetaleans that are morphologically indistinguishable from extant Equisetum and recently discovered anatomically preserved examples strongly suggest an earlier Mesozoic initial diversification. In situ samples of Equisetum thermale sp. nov. from the Upper Jurassic San Agustín hot spring deposit were collected and studied with the use of polished blocks, thin sections, and light microscopy. Equisetum thermale exhibits all the morphological and anatomical characteristics of the extant crown group Equisetum. It shows a mixture of features present in the two extant subgenera, e.g., superficial stomata typical of subgenus Equisetum allied with infrequently ramifying stems typical of subgenus Hippochaete. This appears to ally E. thermale with the least derived extant species in the genus Equisetum bogotense (sister species to the two subgenera). Its association of hydromorphic and xeromorphic characters allowed it to grow as an emergent aquatic in physically and chemically stressed geothermally influenced wetlands, where it formed dense monospecific stands. Equisetum thermale, because it is preserved in situ with intact anatomy, provides clear paleoecological, biological, plus inferred paleoecophysiological evidence of adaptations known in extant species. As the earliest unequivocal member of the genus, E. thermale supports the hypothesis of a Mesozoic origin. Its inferred tolerance of a similar range of stresses (e.g., high salinity, alkalinity, and heavy metal concentrations) to that seen in extant Equisetum suggests early evolution and subsequent maintenance of ecophysiological innovations in the genus.


Determinants of primary medical care quality measured under the new UK contract: cross sectional study.
To identify factors associated with the quality of primary medical care incentivised under the new UK general medical services contract. Cross sectional study. NHS Ayrshire and Arran area, Scotland. 60 general practices. Quality scores reflecting the total points achieved on the 10 clinical domains and holistic care. Univariate and multivariate regression analyses were used to relate quality scores to measures of population characteristics, urban-rural location, general practitioner characteristics, clinical team size and composition, practice characteristics, and income from other sources. Deprivation was associated with higher scores. Quality scores increased with the size of the clinical team. Practices with higher income from other sources had lower quality scores. Practices that were accredited, had training status, or contained younger general practitioners had higher quality scores, but these effects were explained by other associated factors. 53% of the variation in quality scores was explained by a multivariate model, which included measures of deprivation, clinical team size and composition, and financial incentives. Population characteristics showed little association with the quality of primary medical care incentivised under the UK general medical services contract. Larger clinical teams delivered higher quality clinical care, but the nurse-doctor composition of the clinical team did not influence quality. Practices that were more likely to respond to financial incentives because of previous behaviour or lower income from other sources recorded higher quality. If generalisable, the results suggest that initiatives to improve primary medical care quality should focus on the structure and resourcing of providers.


In vivo structures of an intact type VI secretion system revealed by electron cryotomography.
The type VI secretion system (T6SS) is a versatile molecular weapon used by many bacteria against eukaryotic hosts or prokaryotic competitors. It consists of a cytoplasmic bacteriophage tail-like structure anchored in the bacterial cell envelope via a cytoplasmic baseplate and a periplasmic membrane complex. Rapid contraction of the sheath in the bacteriophage tail-like structure propels an inner tube/spike complex through the target cell envelope to deliver effectors. While structures of purified contracted sheath and purified membrane complex have been solved, because sheaths contract upon cell lysis and purification, no structure is available for the extended sheath. Structural information about the baseplate is also lacking. Here, we use electron cryotomography to directly visualize intact T6SS structures inside Myxococcus xanthus cells. Using sub-tomogram averaging, we resolve the structure of the extended sheath and membrane-associated components including the baseplate. Moreover, we identify novel extracellular bacteriophage tail fiber-like antennae. These results provide new structural insights into how the extended sheath prevents premature disassembly and how this sophisticated machine may recognize targets.


Extremely low frequency electromagnetic fields (ELF-EMFs) induce in vitro angiogenesis process in human endothelial cells.
Effects of extremely low frequency (ELF) electromagnetic fields (EMFs) on activation of angiogenesis were analysed using cultured umbilical human vein endothelial cells (HUVECs). The cultures were exposed to a sinusoidal EMF to intensity of 1 mT, 50 Hz for up to 12 h. EMFs increased the degree of endothelial cell proliferation and tubule formation, coupled by an acceleration in the process of wound healing. Since this process is physiologically accompanied by a large modification in the structural organization of actin and focal adhesions, we analyzed the rearrangement of some cytoskeleton elements demonstrating a major reorganization of the fibres and of the focal adhesion complexes after EMF exposure. Finally, Western blot analysis revealed a significant increase in phosphorylation as well as the overall expression of VEGF receptor 2 (KDR/Flk-1) suggesting that EMFs may modulate in vitro some endothelial functions correlated to angiogenesis through signal transduction pathways dependent on VEGF.


PMP1 18-38, a yeast plasma membrane protein fragment, binds phosphatidylserine from bilayer mixtures with phosphatidylcholine: a (2)H-NMR study.
PMP1 is a 38-residue plasma membrane protein of the yeast Saccharomyces cerevisiae that regulates the activity of the H(+)-ATPase. The cytoplasmic domain conformation results in a specific interfacial distribution of five basic side chains, thought to strongly interact with anionic phospholipids. We have used the PMP1 18-38 fragment to carry out a deuterium nuclear magnetic resonance ((2)H-NMR) study for investigating the interactions between the PMP1 cytoplasmic domain and phosphatidylserines. For this purpose, mixed bilayers of 1-palmitoyl, 2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl, 2-oleoyl-sn-glycero-3-phosphoserine (POPS) were used as model membranes (POPC/POPS 5:1, m/m). Spectra of headgroup- and chain-deuterated POPC and POPS phospholipids, POPC-d4, POPC-d31, POPS-d3, and POPS-d31, were recorded at different temperatures and for various concentrations of the PMP1 fragment. Data obtained from POPS deuterons revealed the formation of specific peptide-POPS complexes giving rise to a slow exchange between free and bound PS lipids, scarcely observed in solid-state NMR studies of lipid-peptide/protein interactions. The stoichiometry of the complex (8 POPS per peptide) was determined and its significance is discussed. The data obtained with headgroup-deuterated POPC were rationalized with a model that integrates the electrostatic perturbation induced by the cationic peptide on the negatively charged membrane interface, and a "spacer" effect due to the intercalation of POPS/PMP1f complexes between choline headgroups.


The anomalous currents in the front foils of the JET lost alpha diagnostic KA-2.
We have examined the observed currents in the front foils of the JET Faraday cup lost alpha particle diagnostic KA-2. In particular, we have sought to understand the currents during Ohmic plasmas for which the ion flux at the detectors was initially assumed to be negligible. We have considered two sources of this current: plasma ions (both deuterium and impurity) in the vicinity of the detector (including charge exchange neutrals) and photoemission from scattered UV radiation. Based upon modeling and empirical observation, the latter source appears most likely and, moreover, seems to be applicable to the currents in the front foil during ELMy H-mode plasmas. A very thin gold or nickel foil attached to the present detector aperture is proposed as a solution to this problem, and realistic calculations of expected fluxes of lost energetic neutral beam ions during TF ripple experiments are presented as justification of this proposed solution.


Gender-Specific Effects on Gestational Length and Birth Weight by Early Pregnancy BPA Exposure.
Effects of prenatal exposure to bisphenol A (BPA) on gestational and birth outcomes are controversial. The aim of the study was to evaluate the relationship between prenatal exposure to BPA and birth and gestational outcomes. design, setting, participants, and outcome: Levels of unconjugated (uBPA) and BPA glucuronide in 80 matching samples of pregnant women during the first trimester of pregnancy and at delivery and matching term cord blood obtained from a prospective study conducted at the University of Michigan Hospitals were determined using a methodology validated in the National Institutes of Environmental Health Sciences funded Round Robin study and related to pregnancy outcomes. Highest levels of uBPA were found in maternal term samples followed by first trimester maternal (M1) samples and cord blood. A 2-fold increase in M1 uBPA was associated with 55-g less birth weight when male and female pregnancies were combined and 183-g less birth weight with only female pregnancies. A 2-fold increase in maternal term uBPA was associated with an increased gestational length of 0.7 days for all pregnancies and 1.1 days for only female pregnancies. Higher uBPA exposure levels during first trimester and term are associated with sex-specific reduction in birth weight and increase in gestational length, respectively. Race, parity, and employment have an effect on BPA exposure. Because low birth weight is associated with adverse health outcomes, effect of early pregnancy BPA levels on reducing birth weight highlights the risk posed by developmental exposure to BPA.


Non-smoker exposure to secondhand cannabis smoke. I. Urine screening and confirmation results.
Increased cannabis potency has renewed concerns that secondhand exposure to cannabis smoke can produce positive drug tests. A systematic study was conducted of smoke exposure on drug-free participants. Six experienced cannabis users smoked cannabis cigarettes (5.3% THC in Session 1 and 11.3% THC in Sessions 2 and 3) in a sealed chamber. Six non-smokers were seated with smokers in an alternating manner. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Non-smoking participant specimens (collected 0-34 h) were analyzed with four immunoassays at different cutoff concentrations (20, 50, 75 and 100 ng/mL) and by GC-MS (LOQ = 0.75 ng/mL). No presumptive positives occurred for non-smokers at 100 and 75 ng/mL; a single positive occurred at 50 ng/mL; and multiple positives occurred at 20 ng/mL. Maximum THCCOOH concentrations by GC-MS for non-smokers ranged from 1.3 to 57.5 ng/mL. THCCOOH concentrations generally increased with THC potency, but room ventilation substantially reduced exposure levels. These results demonstrate that extreme cannabis smoke exposure can produce positive urine tests at commonly utilized cutoff concentrations. However, positive tests are likely to be rare, limited to the hours immediately post-exposure, and occur only under environmental circumstances where exposure is obvious.


New Concept of the Encapsulated Follicular Variant of Papillary Thyroid Carcinoma and Its Impact on the Bethesda System for Reporting Thyroid Cytopathology: A Single-Institute Experience.
The encapsulated follicular variant (EFV) of papillary thyroid carcinoma (PTC) is the most discussed entity in thyroid pathology. Recently, the question of whether or not EFV-PTC is a malignant entity has been the subject of renewed discussion in the light of recent molecular and clinical studies. The aim of this study was to analyze the malignancy ratios of each category of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) if EFV-PTC is no longer considered as a malignant entity. Data on thyroid fine-needle aspirations (n = 1,886) with surgical follow-up between 1999 and 2014 were studied. EFV-PTC cases constituted 27% (94/343) of the malignant cases. Malignancy ratios were determined as nondiagnostic, benign, atypia/follicular lesion of undetermined significance, suspicious for follicular neoplasm/follicular neoplasm, suspicious for malignancy, and malignant categories of the TBSRTC in 13, 7, 45, 30, 72 and 98%, respectively. If EFV-PTC was not regarded as malignant, malignancy ratios would decrease to 6.5, 6, 30, 10, 48, and 87% for each category in the same order. The current study showed that the most significant decrease in relative malignancy ratios was seen in the suspicious for follicular neoplasm/follicular neoplasm category (66% relative decrease), but all categories represented a considerable decrease.