On the mechanism for nanoplasmonic enhancement of photon to electron conversion in nanoparticle sensitized hematite films.
Hematite (Fe2O3) is a promising candidate for hydrogen production via water splitting despite the difference in the characteristic lengths for photon absorption and charge carrier transport. Metallic nanoparticles supporting localized surface plasmon resonances (LSPRs), i.e. collective, non-propagating oscillations of electrons excited by an external electric field, are well-suited to improve the optoelectronic properties of hematite, in particular for ultra-thin films. Several mechanisms have been proposed to explain the observed LSPR mediated performance enhancement. In this work, the improvement of incident photon-to-electron conversion efficiency (IPCE) of ultra-thin hematite photoanodes functionalized with Au nanodisks was investigated. The improvement in IPCE at wavelengths close to the bandgap in hematite was found to correlate well with the increase in optical extinction owing to the excitation of LSPR in the nanodisks. Finite-difference time-domain calculations of the near-field distribution around the nanodisks enabled us to elucidate the mechanism behind the IPCE enhancement and its variations with the position of the plasmonic resonance with respect to the bandgap of hematite. Both were attributed to an increased charge generation close to the hematite-electrolyte interface caused by the electric field enhancement in hematite. The results presented here are directly applicable to other semiconductors with similar properties to hematite and are expected to be helpful in future design of optimized photoanodes, where, for instance, functionalization with metallic nanoparticles is combined with material doping and nanostructuring.


[Application of long term video electroencephalogram and resting-state functional magnetic resonance imaging in detection of cognition in patients with benign epilepsy of childhood with centrotemporal spikes].
Objective: To study the relationship between the changes of brain network and cognition in patients with benign epilepsy of childhood with centrotemporal spikes (BECTS) by using long term video electroencephalogram (VEEG) and resting-state functional magnetic resonance imaging (RS-fMRI) technology. Methods: Eleven patients with right-handed were recruited (from April 2015 to September 2016) from epilepsy specialist outpatients and functional department of neurosurgery of Tianjin Medical University General Hospital. They all underwent the long term VEEG monitoring (one sleep cycle was included at least). According to the spike-wave index (SWI) during slow ware sleep, they were divided into two groups: SWI<50% (5 cases) and SWI≥50% (6 cases). All the patients were assessed with cognitional test including language, execution, memory and attention. They also underwent the head MRI, RS-fMRI examinations. Then the results were comparatively analysed. Results: (1)There were no statisticaly significance in sex, age, age of onset, disease course, total number of seizures, years of education (P>0.05). The Full Intelligence Quotient (FIQ) (87±18), Verbal Intelligence Quotient (VIQ) (88±15) and Performance Intelligence Quotient (PIQ) (89±20) of SWI≥50% group were lower than SWI<50% group(118±8, 114±11, 119±5) and the differences were statistically significant(P<0.05). (2)There was a negative correlation between the FIQ (P=0.002), VIQ (P=0.006), PIQ (P=0.001) and SWI. The FIQ, VIQ and PIQ had no correlation with the sex, age, age of onset, disease course, total number of seizures, years of education (P>0.05). (3)Compared with SWI<50% group, SWI≥50% group showed increased regional homogeneity (ReHo) in the bilateral precentral gyrus, premotor area and the subcortical structure, the right temporal lobe and the bilateral insular lobe(P<0.05); while they showed decreased ReHo in the posterior cingulate gyrus, right posterior inferior temporal lobe and right occipital lobe(P<0.05). Conclusion: The change of the brain network which is caused by the paradoxical and constant discharge during slow ware sleep in patients with BECTS may affect the development of cognition.


Effect of transglutaminase on quality and gel properties of pork and fish mince mixtures.
Transglutaminase (TGase) is widely applied in the meat industry, and mixing of meat from various sources is an efficient way to enhance the quality of meat products. In this study, sensory scores, color, gel properties, water holding capacity and microstructure of mince mixtures, treated with 0.4% TGase, were determined to investigate the effect of TGase and mixing ratios (pork/fish, 10:0, 7:3, 5:5, 3:7, 0:10) on quality and gel properties of mince mixtures composed of pork and silver carp (Hypophthalmichthys molitrix). Results indicated that the mixture improved the sensory quality and gel properties of meat products compared to control group. The addition of TGase significantly (p < .05) increased the gel strength, especially at 7:3 ratio of pork and silver carp, in which gel strength reached its maximum and was 10.26%, 64.15% greater than pork with TGase and without TGase respectively, and water holding capacity were greater, and microstructure became more compact. The results suggest the synergetic interaction between proteins of pork and silver carp. TGase increased the interaction, especially for mixing proportion of 7:3 (pork/fish). Those results could be useful for the development of mixed and new meat products in the food industry. Pork and silver carp are two main meat in diet, and mince mixtures can improve the nutrition of meat product. TGase is usually used to enhance the texture and gel properties of meat in industry. The addition of TGase in pork/fish mince mixtures can not only improve the texture, but catalyze the synergetic interaction between proteins from different meat and further enhance gel properties of mice mixtures in a certain ratio. All of that will provide reference for meat processing and development of new meat product.


Thrombocytopenia Impairs Host Defense Against Burkholderia pseudomallei (Melioidosis).
Infection with the gram-negative bacillus Burkholderia pseudomallei (melioidosis) is an important cause of pneumosepsis in Southeast Asia and has a mortality of up to 40%. We aimed to assess the role of platelets in the host response against B. pseudomallei infection. Association between platelet counts and mortality was determined in 1160 patients with culture-proven melioidosis. Mice treated with (low- or high-dose) platelet-depleting antibody were inoculated intranasally with B. pseudomallei and killed. Additional studies using functional glycoprotein Ibα-deficient mice were conducted. Thrombocytopenia was present in 31% of patients at admission and predicted mortality in melioidosis patients even after adjustment for confounders. In our murine-melioidosis model, platelet counts decreased, and mice treated with a platelet-depleting antibody showed enhanced mortality and higher bacterial loads compared to mice with normal platelet counts. Low platelet counts had a modest impact on early-pulmonary neutrophil influx. Reminiscent of their role in hemostasis, platelet depletion impaired vascular integrity, resulting in early lung bleeding. Glycoprotein Ibα-deficient mice had reduced platelet counts during B. pseudomallei infection together with an impaired local host defense in the lung. Thrombocytopenia predicts mortality in melioidosis patients and, during experimental melioidosis, platelets play a protective role in both innate immunity and vascular integrity.


[Side effects of specific immunotherapy in patients with hymenoptera venom allergy].
The aim of this study was to estimate safety of specific immunotherapy to insects' venom. The frequency of side effects was compared in two groups of patients: subjects with hypersensitivity to insects' venom only and patients with allergy to other allergens. In the examined group of 32 patients with Hymenoptera venoms allergy skin prick tests with common aeroallergens were performed in 30 subjects. In 18 patients (60%) at least one test was positive. In 23 patients (71.9%) immunotherapy with Hymenoptera venom was connected with side effects observed just after administration of vaccine. They were mainly local reactions (itching, redness and oedema). In 6 patients late reactions were observed. No correlation has been found between frequency of side effects of immunotherapy and positive results of skin prick tests. However systemic reactions were revealed only in the group of patients with at least one positive result of skin prick tests.


Effect of sodium fluoride on the viability and growth of Streptococcus mutans.
A fluoride-sensitive (FS) strain of Streptococcus mutans and a laboratory-induced fluoride-resistant (FR) offspring were compared for the effects of sodium fluoride on viability and growth. There was a significant fluoride-related loss of viability in resting cell suspensions of the FS strain during a 47-hour exposure to fluoride levels above 75 ppm that was not encountered with the FR strain. The addition of 300 ppmF to actively growing six-hour broth cultures almost totally arrested the growth of the FS strain, while only slightly reducing that of the FR culture. The addition of 600 ppmF immediately terminated FS growth, and greatly reduced the rate and maximum growth of FR cultures.


A Self-Disguised Nanospy for Improving Drug Delivery Efficiency via Decreasing Drug Protonation.
Nanoscale drug carriers play a crucial role in reducing side effects of chemotherapy drugs. However, the mononuclear phagocyte system (MPS) and the drug protonation after nanoparticles (NPs) burst release still limit the drug delivery efficiency. In this work, a self-disguised Nanospy is designed to overcome this problem. The Nanospy is composed of: i) poly (lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) loading doxorubicin is the core structure of the Nanospy. ii) CD47 mimic peptides (CD47p) is linked to NPs which conveyed the "don't eat me" signal. iii) 4-(2-aminoethyl) benzenesulfonamide (AEBS) as the inhibitor of Carbonic anhydrase IX (CAIX) linked to NPs. Briefly, when the Nanospy circulates in the bloodstream, CD47p binds to the regulatory protein α (SIRPα) on the surface of macrophages, which causes the Nanospy escapes from phagocytosis. Subsequently, the Nanospy enriches in tumor and the AEBS reverses the acidic microenvironment of tumor. Due to above characteristics, the Nanospy reduces liver macrophage phagocytosis by 25% and increases tumor in situ DOX concentration by 56% compared to PLGA@DOX treatment. In addition, the Nanospy effectively inhibits tumor growth with a 63% volume reduction. This work presents a unique design to evade the capture of MPS and overcomes the influence of acidic tumor microenvironment (TME) on weakly alkaline drugs.


Tuberculosis knowledge, attitudes, and practices among northern Ethiopian prisoners: Implications for TB control efforts.
Although awareness is an important component in tuberculosis (TB) control, we do not know how much Ethiopian prisoners know about TB. This study assessed the level of knowledge, attitudes, and practices (KAP) of prisoners about TB in eight northern Ethiopian prisons. Data were collected cross-sectionally from 615 prisoners using a standardized questionnaire between March and May 2016. The outcome variables were defined considering the basic elements about TB. Out of 615 prisoners, only 37.7% mentioned bacteria as a cause of TB while 21.7% related TB to exposure to cold wind. Eighty-eight per cent correctly mentioned the aerial route of TB transmission and 27.3% had perceived stigma towards TB. The majority (63.7%) was not aware of the possibility of getting multi-drug-resistant strains when they would not adhere to treatment. Overall, only 24% knew the basic elements about TB, 41% had favorable attitudes, and 55% had a good practice. Prisoners who were urban residents were generally more knowledgeable than rural residents (adjusted OR = 2.16; 95% CI = 1.15-4.06). Illiterates were found to be less knowledgeable (adjusted OR = 0.17; 95% CI = 0.06-0.46), less likely to have a favorable attitude (adjusted OR = 0.31; 95% CI = 0.15-0.64), and less good practice (adjusted OR = 0.35; 95% CI = 0.18-0.69). Significant differences were also observed between the different study prisons. Knowledge of prisoners regarding the cause of TB and consequences of non-adherence to TB treatment was low. Knowledge on the transmission, symptoms, and prevention was fairly high. Health education interventions, focused on the cause and the translation of the knowledge to appropriate practices, are needed in all the study prisons. Special attention should be given to less educated prisoners, and to prisons with a high number of prisoners and those in remote areas.


Exposure of Somatic Cells to Cytoplasm Extracts of Porcine Oocytes Induces Stem Cell-Like Colony Formation and Alters Expression of Pluripotency and Chromatin-Modifying Genes.
Cell permeabilization followed by exposure to cytoplasmic extracts of oocytes has been proposed as an alternative to transduction of transcription factors for inducing pluripotency in cultured somatic cells. The main goal in this study was to investigate the effect of treating porcine fibroblast cells with cytoplasmic extracts of GV-stage oocyte (OEx) followed by inhibition of histone deacetylases with Scriptaid (Scrip) on the formation of stem cell-like colonies and expression of genes encoding pluripotency and chromatin-modifying enzymes. Stem cell-like colonies start developing ∼2 weeks after treatment in cells exposed to OEx or OEx + Scrip. The number of cell colonies at the first day of appearance and 48 hours later was also similar between OEx and OEx + Scrip treatments. Transcripts for Nanog, Rex1, and c-Myc genes were detected in most cell samples that were analyzed on different days after OEx treatment. However, Sox2 transcripts were not detected and only a small proportion of samples had detectable levels of Oct4 mRNA after OEx treatment. A similar pattern of transcripts for pluripotency genes was observed in cells treated with OEx alone or OEx + Scrip. Transcript levels for Dnmt1 and Ezh2 were reduced at Day 3 after treatment in cells exposed to OEx. These findings revealed that: (a) exposure to OEx can induce a partial reprogramming of fibroblast cells toward pluripotency, characterized by colony formation and activation of pluripotency genes; and (b) inhibition of histone deacetylases does not improve the reprogramming effect of OEx treatment.


Salmonella genomic island 1 (SGI1) reshapes the mating apparatus of IncC conjugative plasmids to promote self-propagation.
IncC conjugative plasmids and Salmonella genomic island 1 (SGI1) and relatives are frequently associated with multidrug resistance of clinical isolates of pathogenic Enterobacteriaceae. SGI1 is specifically mobilized in trans by IncA and IncC plasmids (commonly referred to as A/C plasmids) following its excision from the chromosome, an event triggered by the transcriptional activator complex AcaCD encoded by these helper plasmids. Although SGI1 is not self-transmissible, it carries three genes, traNS, traHS and traGS, coding for distant homologs of the predicted mating pore subunits TraNC, TraHC and TraGC, respectively, encoded by A/C plasmids. Here we investigated the regulation of traNS and traHGS and the role of these three genes in the transmissibility of SGI1. Transcriptional fusion of the promoter sequences of traNS and traHGS to the reporter gene lacZ confirmed that expression of these genes is inducible by AcaCD. Mating experiments using combinations of deletion mutants of SGI1 and the helper IncC plasmid pVCR94 revealed complex interactions between these two mobile genetic elements. Whereas traNC and traHGC are essential for IncC plasmid transfer, SGI1 could rescue null mutants of each individual gene revealing that TraNS, TraHS and TraGS are functional proteins. Complementation assays of individual traC and traS mutants showed that not only do TraNS/HS/GS replace TraNC/HC/GC in the mating pore encoded by IncC plasmids but also that traGS and traHS are both required for SGI1 optimal transfer. In fact, remodeling of the IncC-encoded mating pore by SGI1 was found to be essential to enhance transfer rate of SGI1 over the helper plasmid. Furthermore, traGS was found to be crucial to allow DNA transfer between cells bearing IncC helper plasmids, thereby suggesting that by remodeling the mating pore SGI1 disables an IncC-encoded entry exclusion mechanism. Hence traS genes facilitate the invasion by SGI1 of cell populations bearing IncC plasmids.


Toward computational cumulative biology by combining models of biological datasets.
A main challenge of data-driven sciences is how to make maximal use of the progressively expanding databases of experimental datasets in order to keep research cumulative. We introduce the idea of a modeling-based dataset retrieval engine designed for relating a researcher's experimental dataset to earlier work in the field. The search is (i) data-driven to enable new findings, going beyond the state of the art of keyword searches in annotations, (ii) modeling-driven, to include both biological knowledge and insights learned from data, and (iii) scalable, as it is accomplished without building one unified grand model of all data. Assuming each dataset has been modeled beforehand, by the researchers or automatically by database managers, we apply a rapidly computable and optimizable combination model to decompose a new dataset into contributions from earlier relevant models. By using the data-driven decomposition, we identify a network of interrelated datasets from a large annotated human gene expression atlas. While tissue type and disease were major driving forces for determining relevant datasets, the found relationships were richer, and the model-based search was more accurate than the keyword search; moreover, it recovered biologically meaningful relationships that are not straightforwardly visible from annotations-for instance, between cells in different developmental stages such as thymocytes and T-cells. Data-driven links and citations matched to a large extent; the data-driven links even uncovered corrections to the publication data, as two of the most linked datasets were not highly cited and turned out to have wrong publication entries in the database.


Cellulose, Chitosan and Keratin Composite Materials: Facile and Recyclable Synthesis, Conformation and Properties.
A method was developed in which cellulose (CEL) and/or chitosan (CS) were added to keratin (KER) to enable [CEL/CS+KER] composites formed to have better mechanical strength and wider utilization. Butylmethylimmidazolium chloride ([BMIm+Cl-]), an ionic liquid, was used as the sole solvent, and because the majority of [BMIm+Cl-] used (at least 88%) was recovered, the method is green and recyclable. FTIR, XRD, 13C CP-MAS NMR and SEM results confirm that KER, CS and CEL remain chemically intact and distributed homogeneously in the composites. We successfully demonstrate that the widely used method based on the deconvolution of the FTIR bands of amide bonds to determine secondary structure of proteins is relatively subjective as the conformation obtained is strongly dependent on the choice of parameters selected for curve fitting. A new method, based on the partial least squares regression analysis (PLSR) of the amide bands, was developed, and proven to be objective and can provide more accurate information. Results obtained with this method agree well with those by XRD, namely they indicate that although KER retains its second structure when incorporated into the [CEL+CS] composites, it has relatively lower α-helix, higher β-turn and random form compared to that of the KER in native wool. It seems that during dissolution by [BMIm+Cl-], the inter- and intramolecular forces in KER were broken thereby destroying its secondary structure. During regeneration, these interactions were reestablished to reform partially the secondary structure. However, in the presence of either CEL or CS, the chains seem to prefer the extended form thereby hindering reformation of the α-helix. Consequently, the KER in these matrices may adopt structures with lower content of α-helix and higher β-sheet. As anticipated, results of tensile strength and TGA confirm that adding CEL or CS into KER substantially increase the mechanical strength and thermal stability of the [CS/CEL+KER] composites.


Privacy and the Human Genome Project.
The Human Genome Project has raised many issues regarding the contributions of genetics to a variety of diseases and societal conditions. With genetic testing now easily conducted with lowered costs in nonmedical domains, a variety of privacy issues must be considered. Such testing will result in the loss of significant privacy rights for the individual. Society must now consider such issues as the ownership of genetic data, confidentiality rights to such information, limits placed on genetic screening, and legislation to control genetic testing and its applications. There is often a conflict between individual rights to privacy and the need for societal protection.


Marijuana use and mortality.
The purpose of this study was to examine the relationship of marijuana use to mortality. The study population comprised 65171 Kaiser Permanente Medical Care Program enrollees, aged 15 through 49 years, who completed questionnaires about smoking habits, including marijuana use, between 1979 and 1985. Mortality follow-up was conducted through 1991. Compared with nonuse or experimentation (lifetime use six or fewer times), current marijuana use was not associated with a significantly increased risk of non-acquired immunodeficiency syndrome (AIDS) mortality in men (relative risk [RR] = 1.12, 95% confidence interval [CI] = 0.89, 1.39) or of total mortality in women (RR = 1.09, 95% CI = 0.80, 1.48). Current marijuana use was associated with increased risk of AIDS mortality in men (RR = 1.90, 95% CI = 1.33, 2.73), an association that probably was not causal but most likely represented uncontrolled confounding by male homosexual behavior. This interpretation was supported by the lack of association of marijuana use with AIDS mortality in men from a Kaiser Permanente AIDS database. Relative risks for ever use of marijuana were similar. Marijuana use in a prepaid health care-based study cohort had little effect on non-AIDS mortality in men and on total mortality in women.


Gender-stratified models to examine the relationship between financial hardship and self-reported oral health for older US men and women.
We evaluated the relationship between financial hardship and self-reported oral health for older men and women. We focused on adults in the 2008 Health and Retirement Study (n = 1,359). The predictor variables were 4 financial hardship indicators. We used Poisson regression models to estimate the prevalence ratio of poor self-reported oral health. In the non-gender-stratified model, number of financial hardships was not significantly associated with self-reported oral health. Food insecurity was associated with a 12% greater prevalence of poor self-reported oral health (95% confidence interval [CI] = 1.04, 1.21). In the gender-stratified models, women with 3 or more financial hardships had a 24% greater prevalence of poor self-reported oral health than women with zero (95% CI = 1.09, 1.40). Number of hardships was not associated with self-reported oral health for men. For men, skipping medications was associated with 50% lower prevalence of poor self-reported oral health (95% CI = 0.32, 0.76). Number of financial hardships was differentially associated with self-reported oral health for older men and women. Most financial hardship indicators affected both genders similarly. Future interventions to improve vulnerable older adults' oral health should account for gender-based heterogeneity in financial hardship experiences.


Prevalence of depression in patients with cancer.
Depression is the psychiatric syndrome that has received the most attention in individuals with cancer. The study of depression has been a challenge because symptoms occur on a broad spectrum that ranges from sadness to major affective disorder and because mood change is often difficult to evaluate when a patient is confronted by repeated threats to life, is receiving cancer treatments, is fatigued, or is experiencing pain. Although many research groups have assessed depression in cancer patients since the 1960s, the reported prevalence (major depression, 0%-38%; depression spectrum syndromes, 0%-58%) varies significantly because of varying conceptualizations of depression, different criteria used to define depression, differences in methodological approaches to the measurement of depression, and different populations studied. Depression is highly associated with oropharyngeal (22%-57%), pancreatic (33%-50%), breast (1.5%-46%), and lung (11%-44%) cancers. A less high prevalence of depression is reported in patients with other cancers, such as colon (13%-25%), gynecological (12%-23%), and lymphoma (8%-19%). This report reviews the prevalence of depression in cancer patients throughout the course of cancer.


The personal experience of living with chronic heart failure: a qualitative meta-synthesis of the literature.
To determine, from a systematic literature review, the experience of living with heart failure and to propose some practice guidelines and research questions. Chronic heart failure has been one of the fastest growing illnesses in recent decades, with almost 23 million people affected worldwide. This complex syndrome has multiple causes and appears when underlying heart disease is advanced. Currently, heart failure has no cure and leads to a significant deterioration in patients' quality of life. Qualitative meta-synthesis. A qualitative meta-synthesis was conducted to extract and analyse qualitative research from the Cochrane, PubMed, CINAHL, PsycINFO, Web of Science and Cuiden databases. Snowball sampling and a manual search were performed to identify other relevant studies. Twenty-five qualitative studies were selected. The findings indicate that there are three main themes that describe the phenomenon. The first theme refers to the experiences related to the beginning of the process. The second theme is connected with the effects on the person: physical, emotional, social and spiritual changes. The third theme is linked with how to live with heart failure despite the illness, including the adjustment and coping process and how external resources can help them to manage. Heart failure has a major impact on the entire person, but some areas have not been addressed. By creating new tools to understand and evaluate the impact of this illness and interventions that prevent or improve some situations, we can promote the well-being and the quality of life of this population. Nurses must have a personal knowledge of the experiences and needs of the patients. To do this, nurses should create care environments that promote an exchange of experiences and knowledge between the nurse and the patient and family.


Novel luminescent metal-organic frameworks [Eu2L3(DMSO)2(MeOH)2] x 2 DMSO x 3 H2O and [Zn2L2(DMSO)2] x 1.6 H2O (L = 4,4'-ethyne-1,2-diyldibenzoate).
Novel metal-organic frameworks [Eu2L3(DMSO)2(MeOH)2] x 2 DMSO x 3 H2O, 1, and [Zn2L2(DMSO)2] x 1.6 H2O, 2, (L = 4,4'-ethyne-1,2-diyldibenzoate) have been synthesized and structurally characterized. Compound 1 is a 3D open framework while 2 features interpenetrating 2D sheets in the crystal lattice. Both compounds have been characterized with X-ray crystallography, elemental analysis, and thermogravimetric analysis. Compounds 1 and 2 are red and blue-green luminescent, respectively, in the solid state at ambient temperature. Thermogravimetric analysis implies that the extensive interpenetration stabilizes the lattice of 2, although it diminishes the porosity at the same time. The luminescence of 1 can be reversibly quenched and restored by the addition and removal of iodine.


Why hospital design matters: A narrative review of built environments research relevant to stroke care.
Healthcare facilities are among the most expensive buildings to construct, maintain, and operate. How building design can best support healthcare services, staff, and patients is important to consider. In this narrative review, we outline why the healthcare environment matters and describe areas of research focus and current built environment evidence that supports healthcare in general and stroke care in particular. Ward configuration, corridor design, and staff station placements can all impact care provision, staff and patient behavior. Contrary to many new ward design approaches, single-bed rooms are neither uniformly favored, nor strongly evidence-based, for people with stroke. Green spaces are important both for staff (helping to reduce stress and errors), patients and relatives, although access to, and awareness of, these and other communal spaces is often poor. Built environment research specific to stroke is limited but increasing, and we highlight emerging collaborative multistakeholder partnerships (Living Labs) contributing to this evidence base. We believe that involving engaged and informed clinicians in design and research will help shape better hospitals of the future.


[Preparation of samples for gas-chromatographic determination of fatty acids: direct transesterification of lipids of dry biological sample is preferred in comparison with the methods employing preliminary lipid extraction.]
Different methods of sample preparation and derivatization were compared from the point of view of product yield, speed and convenience of the technique used. Fatty acid determination in absolutely dry objects (biochemical preparations, food protein isolates, lyophilized microbial biomass) may be performed easily with the use of Folch method provided that 4-component system "chloroform/ methanol/water/acetic acid" was employed. Nevertheless, we ould not find any real advantages of classical Folch or Hara-Radin extraction method variants when compared to simple non-extraction technique (which consists in direct trans-esterification of dried biomaterial due to sequential sample treating with sodium methoxide and boron trifluoride methanolic solutions). The letter method, being completely universal, provides considerable increase of fatty esters yield, sample preparation is noticeably simplified and accelerated (becoming much more economical). It's "dry blood spot" variant (using cellulose or, preferably, fluoroplast filter paper disks) seems to be extremely convenient for laboratory routine analysis of liquid biological samples, allowing to exclude not only their liquid-liquid extraction but also the stage of vacuum drying. Unlike the methods of Folch and Hara-Radin, the non-extraction method does not necessarily require the homogenization of the biological material, that is, it's grinding to fragments of micron size. Direct derivatization method provides noticeably better parameters of fatty acids yield even for relatively large particles - 0.2-1.0 mm - of the test material (in comparison with those parameters observed upon extraction of micron size homogenizates by the Folch method in its most advanced modifications).


The interaction between temporal grouping and phonotactic chunking in short-term serial order memory for novel verbal sequences.
The current study investigated the ways long-term memory contributes to short-term serial order memory of novel verbal sequences, focusing on long-term knowledge of bi-element frequency, that is, co-occurrence frequency of two consecutive elements in a linguistic environment. Participants performed two types of immediate serial recall of nine-element (nine-mora) sequences: low bi-mora frequency sequences where all eight associations between the nine morae were low frequency, and mixed bi-mora frequency sequences, with high-frequency associations for six of the eight bi-morae. Experiment 1 confirmed the bi-directional bi-mora frequency effect, meaning better recall performance for morae having high-frequency association with either the preceding mora (forward association) or the following mora (backward association). In Experiment 2, two temporal pauses were inserted in each list to disrupt high-frequency associations with the preceding mora or the following mora. The results showed that the bi-element frequency effect diminished when the high-frequency backward association was disrupted but the effect remained when the high-frequency forward association was disrupted. We discuss possible mechanisms underlying the asymmetric influence of temporal pauses on interactions between short-term memory and linguistic long-term memory.


Prevalence and associated risk factors of dyslexic children in a middle-sized city of China: a cross-sectional study.
There are many discussions about dyslexia based on studies conducted in western countries, and some risk factors to dyslexia, such as gender and home literacy environment, have been widely accepted based on these studies. However, to our knowledge, there are few studies focusing on the risk factors of dyslexia in China. Therefore, the aim of our study was to investigate the prevalence of dyslexia and its potential risk factors. A cross-sectional study was conducted in Qianjiang, a city in Hubei province, China. Two stages sampling strategy was applied to randomly selected 5 districts and 9 primary schools in Qianjiang. In total, 6,350 students participated in this study and there were 5,063 valid student questionnaires obtained for the final analyses. Additional questionnaires (such as Dyslexia Checklist for Chinese Children and Pupil Rating Scale) were used to identify dyslexic children. The chi-square test and multivariate logistic regression were employed to reveal the potential risk factors to dyslexia. Our study revealed that the prevalence of dyslexia was 3.9% in Qianjiang city, which is a middle-sized city in China. Among dyslexic children, the gender ratio (boys to girls) was nearly 3∶1. According to the P-value in the multivariate logistic regression, the gender (P<0.01), mother's education level (P<0.01), and learning habits (P<0.01) (active learning, scheduled reading time) were associated with dyslexia. The prevalence rate of dyslexic children in middle-sized cities is 3.9%. The potential risk factors of dyslexic children revealed in this study will have a great impact on detecting and treating dyslexic children in China as early as possible, although more studies are still needed to further investigate the risk factors of dyslexic children in China.


Blood parameters of dwarf and normal pullets from growth selected lines before and after Escherichia coli challenge.
Two experiments were conducted to study the hematological differences and the effect of challenge with Escherichia coli on the hemopoietic system among dwarfs and their normal sisters in lines selected for high and low juvenile body weight. Erythrocyte counts, packed cell volumes, and hemoglobin concentrations were significantly higher to dwarf than for normal pullets, while no such differences were noted for mean corpuscular volume, mean corpuscular hemoglobin and hemoglobin concentration. Dwarfs had a significantly lower erythrocyte sedimentation rate than normal pullets. The effect of challenge with E. coli was evident in all the groups. Body weight decreased and leucocyte counts increased significantly. Lymphopenia, accompanied by heterophilia and a consequent increase in H:L ratio was the conspicuous effect of the challenge with E. coli indicating a polymorphonuclear response. Forty-eight hours after challenge the differential response of lines and genotypes to heterophilia was uniform. The hematological data suggest that the dw gene may not contribute to resistance to bacterial diseases. Mortality and autopsy lesions data indicate that the dw gene had a deleterious effect in the low weight but not in the high weight line, suggesting that its influence on the traits measured is dependent upon the genetic background of the population.


The genetic diversity of Mycobacterium tuberculosis strains in Thailand studied by amplification of DNA segments containing direct repetitive sequences.
To develop and use a polymerase chain reaction (PCR) method for studying the genetic diversity of Mycobacterium tuberculosis. Two polymorphic DNA segments of M. tuberculosis H37Rv were identified and sequenced. Primers were then designed for simultaneous amplification of both polymorphic segments. The method was used for studying 179 clinical isolates of M. tuberculosis that had been previously characterized by Southern hybridization with IS6110. Both polymorphic segments contained direct repetitive sequences. In one segment the direct repetitive sequences were within the putative coding sequence of alpha-isopropylmalate synthase gene. After amplifying both segments of the 179 isolates, 40 patterns of PCR products could be identified. The method was able to differentiate 38 IS6110-single-banded isolates into 23 types. Most of the isolates belonging to the Beijing family had PCR products identical to the H37Rv strain. The PCR products of the members of the Nonthaburi group were similar to each other. These results agree with the hypothesis that the members of the Beijing family and the Nonthaburi group descended from two common ancestors. The PCR method might be useful for differentiating strains of M. tuberculosis that contain a single copy of IS6110.


NRF2 activators inhibit influenza A virus replication by interfering with nucleo-cytoplasmic export of viral RNPs in an NRF2-independent manner.
In addition to antioxidative and anti-inflammatory properties, activators of the cytoprotective nuclear factor erythroid-2-like-2 (NRF2) signaling pathway have antiviral effects, but the underlying antiviral mechanisms are incompletely understood. We evaluated the ability of the NRF2 activators 4-octyl itaconate (4OI), bardoxolone methyl (BARD), sulforaphane (SFN), and the inhibitor of exportin-1 (XPO1)-mediated nuclear export selinexor (SEL) to interfere with influenza virus A/Puerto Rico/8/1934 (H1N1) infection of human cells. All compounds reduced viral titers in supernatants from A549 cells and vascular endothelial cells in the order of efficacy SEL>4OI>BARD = SFN, which correlated with their ability to prevent nucleo-cytoplasmic export of viral nucleoprotein and the host cell protein p53. In contrast, intracellular levels of viral HA mRNA and nucleocapsid protein (NP) were unaffected. Knocking down mRNA encoding KEAP1 (the main inhibitor of NRF2) or inactivating the NFE2L2 gene (which encodes NRF2) revealed that physiologic NRF2 signaling restricts IAV replication. However, the antiviral effect of all compounds was NRF2-independent. Instead, XPO1 knock-down greatly reduced viral titers, and incubation of Calu3 cells with an alkynated 4OI probe demonstrated formation of a covalent complex with XPO1. Ligand-target modelling predicted covalent binding of all three NRF2 activators and SEL to the active site of XPO1 involving the critical Cys528. SEL and 4OI manifested the highest binding energies, whereby the 4-octyl tail of 4OI interacted extensively with the hydrophobic groove of XPO1, which binds nuclear export sequences on cargo proteins. Conversely, SEL as well as the three NRF2 activators were predicted to covalently bind the functionally critical Cys151 in KEAP1. Blocking XPO1-mediated nuclear export may, thus, constitute a "noncanonical" mechanism of anti-influenza activity of electrophilic NRF2 activators that can interact with similar cysteine environments at the active sites of XPO1 and KEAP1. Considering the importance of XPO1 function to a variety of pathogenic viruses, compounds that are optimized to inhibit both targets may constitute an important class of broadly active host-directed treatments that embody anti-inflammatory, cytoprotective, and antiviral properties.


Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights.
Lantibiotic synthetases are remarkable biocatalysts generating conformationally constrained peptides with a variety of biological activities by repeatedly utilizing two simple posttranslational modification reactions: dehydration of Ser/Thr residues and intramolecular addition of Cys thiols to the resulting dehydro amino acids. Since previously reported lantibiotic synthetases show no apparent homology with any other known protein families, the molecular mechanisms and evolutionary origin of these enzymes are unknown. In this study, we present a novel class of lanthionine synthetases, termed LanL, that consist of three distinct catalytic domains and demonstrate in vitro enzyme activity of a family member from Streptomyces venezuelae. Analysis of individually expressed and purified domains shows that LanL enzymes install dehydroamino acids via phosphorylation of Ser/Thr residues by a protein kinase domain and subsequent elimination of the phosphate by a phosphoSer/Thr lyase domain. The latter has sequence homology with the phosphothreonine lyases found in various pathogenic bacteria that inactivate host mitogen activated protein kinases. A LanC-like cyclase domain then catalyzes the addition of Cys residues to the dehydro amino acids to form the characteristic thioether rings. We propose that LanL enzymes have evolved from stand-alone protein Ser/Thr kinases, phosphoSer/Thr lyases, and enzymes catalyzing thiol alkylation. We also demonstrate that the genes for all three pathways to lanthionine-containing peptides are widespread in Nature. Given the remarkable efficiency of formation of lanthionine-containing polycyclic peptides and the latter's high degree of specificity for their cognate cellular targets, it is perhaps not surprising that (at least) three distinct families of polypeptide sequences have evolved to access this structurally and functionally diverse class of compounds.


Two new cavernicolous Pselaphinae (Coleoptera: Staphylinidae) from southern China.
Two new cavernicolous pselaphines, Araneibatrus curvitibialis Yin and Zhou, sp. n. and Tribasodites biyun Yin and Zhou, sp. n., are described from southern China, with diagnostic characters illustrated. Both new species can be readily distinguished from their respective congeners by the male dimorphic features on the antennae, legs, and (or) metaventrite, as well as by the configurations of the aedeagi.


Infection Characteristics of Rice Stripe Mosaic Virus in the Body of the Vector Leafhoppers.
Rice stripe mosaic virus (RSMV), a novel species of Cytorhabdovirus, is transmitted by the leafhopper Recilia dorsalis in a persistent-propagative manner. In this study, we firstly confirmed that N protein of RSMV is a component of viroplasm and virion in vector culture cells of R. dorsalis. Confocal microscopy revealed that RSMV initially accumulated in epithelial cells of the filter chamber of R. dorsalis, from where it proceeded to the visceral muscles surrounding the filter chamber. Subsequently, RSMV spread quickly throughout the suspensory ligament to the salivary glands. Meanwhile, RSMV spread from the filter chamber to midgut, hindgut, esophagus, hemolymph, and central nervous system. We further observed that RSMV particles displayed as non-enveloped form when propagating in cytoplasm of different tissues, and became enveloped when spread within insect body by electron microscopy. Additionally, we found that the leafhopper Nephotettix virescens was also able to acquire and transmit RSMV. These results clarified the infection characteristics of RSMV in its leafhopper vectors, which will help guide the formulation of RSMV prevention and control strategies.


Can long-range microsatellite data be used to predict short-range linkage disequilibrium?
The distribution of linkage disequilibrium (LD) across the genome is highly complex. Little is known about the relationship between long-range and short-range LD in a genomic region. We assessed whether a dense set of microsatellite data could be used to predict short-range LD in family samples. We analyzed intermarker LD in data derived from chromosomal regions 18q22 and 10q25-26, densely genotyped with microsatellite markers. The pattern of LD was highly heterogeneous within and between both chromosomal regions. On 10q25-26, very little LD was detected. On 18q22, where marker density was higher, many marker pairs were in LD. We modeled the decay of LD over distance in this region. A classical model accounted for most of the relationship between LD and distance (R (2)=63%). We used this model to predict the proportion of markers expected to show useful levels of LD at short distances. This prediction agreed with estimates based on single-nucleotide polymorphism (SNP) marker genotypes in the region. Both microsatellite and SNP data predict that about 80% of marker pairs would display levels of LD that are useful for association studies at distances of up to 15 kb in this region. These projections also agree with levels of LD directly measured in a 10 kb set of SNP genotypes generated in a nearby region of finished sequence. Our results suggest that existing sets of microsatellite data, if sufficiently dense, may be used to develop good initial estimates of the density of additional markers needed to screen a region for disease alleles by association analysis.


S-state dependence of the calcium requirement and binding characteristics in the oxygen-evolving complex of photosystem II.
The functional role of the Ca (2+) ion in the oxygen-evolving complex of photosystem II is not yet clear. Current models explain why the redox cycle of the complex would be interrupted after the S 3 state without Ca (2+), but the literature shows that it is interrupted after the S 2 state. Reinterpretation of the literature on methods of Ca (2+) depletion [Miqyass, M., van Gorkom, H. J., and Yocum, C. F. (2007) Photosynth. Res. 92, 275-287] led us to propose that all S-state transitions require Ca (2+). Here we confirm that interpretation by measurements of flash-induced S-state transitions in UV absorbance. The results are explained by a cation exchange at the Ca (2+) binding site that, in the absence of the extrinsic PsbP and PsbQ polypeptides, can occur in minutes in low S-states and in seconds in high S-states, depending on the concentration of the substituting cation. In the S 2(K (+)) or S 2(Na (+)) state a slow conformational change occurs that prevents recovery of the slow-exchange situation on return to a lower S-state but does not inhibit the S-state cycle in the presence of Ca (2+). The ratio of binding affinities for monovalent vs divalent cations increases dramatically in the higher S-states. With the possible exception of S 0 to S 1, all S-state transitions specifically require Ca (2+), suggesting that Ca (2+)-bound H 2O plays an essential role in a H (+) transfer network required for H (+)-coupled electron transfer from the Mn cluster to tyrosine Z.


G-protein-coupled receptors and melanoma.
G-protein-coupled receptors (GPCR) are the largest family of receptors with over 500 members. Evaluation of GPCR gene expression in primary human tumors identified over-expression of GPCR in several tumor types. Analysis of cancer samples in different disease stages also suggests that some GPCR may be involved in early tumor progression and others may play a critical role in tumor invasion and metastasis. Currently, >50% of drug targets to various human diseases are based on GPCR. In this review, the relationships between several GPCR and melanoma development and/or progression will be discussed. Finally, the possibility of using one or more of these GPCR as therapeutic targets in melanoma will be summarized.


Incremental Local Distribution-Based Clustering Using Bayesian Adaptive Resonance Theory.
Most of the existing Bayesian clustering algorithms perform well on the balanced data. When the data are highly imbalanced, these Bayesian clustering algorithms tend to strongly favor the larger clusters, but provide a notably low detection of the smaller clusters. In this paper, we present an incremental local distribution-based clustering algorithm with the Bayesian adaptive resonance theory (ILBART). This algorithm is developed to adapt itself to a changing environment without using any predefined parameters. The algorithm not only accurately finds the clusters, even in data sets with a severely imbalanced distribution, but also efficiently processes the dynamic data according to the evolving relationships among the clusters. We test our proposed algorithm with experiments conducted on several imbalanced data sets. The experimental results show that our proposed algorithm performs well for clustering imbalanced data and can also obtain a better performance than many other relevant clustering algorithms in several performance indices.


Lack of IgA antineutrophil cytoplasmic antibodies in Henoch-Schönlein purpura and IgA nephropathy.
To verify whether IgA antineutrophil cytoplasmic antibody (ANCA) represents a serologic marker in Henoch-Schönlein purpura (HPS), we examined sera from 41 patients with the disease. Control sera from 28 patients with primary IgA nephropathy (IgA-N), 26 IgG-ANCA-positive vasculitis, and 28 normal controls were also studied. An increased IgA binding to neutrophil cytoplasmic extracts but not to purified ANCA antigens was found in 12.2-14.6% of HSP patients and in 14.3-21.4% of IgA-N patients versus 3.5% of normal controls. IgA binding to neutrophil cytoplasmic extracts correlated with serum IgA levels, IgA-rheumatoid factor, and IgA-fibronectin binding capacity. Moreover, low amounts of IgG and fibronectin were detected as contaminants in neutrophil cytoplasmic extracts and fibronectin could partly inhibit the binding of IgA to "crude" extracts. We conclude that IgA-ANCA are neither diagnostically nor immunologically specific in HSP and IgA-N. Several factors present in the sera of patients with IgA-related nephropathies seem to contribute to the "false-positive" IgA-ANCA demonstrable in these patients.


Agent-based Bayesian approach to monitoring the progress of invasive species eradication programs.
Eradication of an invasive species can provide significant environmental, economic, and social benefits, but eradication programs often fail. Constant and careful monitoring improves the chance of success, but an invasion may seem to be in decline even when it is expanding in abundance or spatial extent. Determining whether an invasion is in decline is a challenging inference problem for two reasons. First, it is typically infeasible to regularly survey the entire infested region owing to high cost. Second, surveillance methods are imperfect and fail to detect some individuals. These two factors also make it difficult to determine why an eradication program is failing. Agent-based methods enable inferences to be made about the locations of undiscovered individuals over time to identify trends in invader abundance and spatial extent. We develop an agent-based Bayesian method and apply it to Australia's largest eradication program: the campaign to eradicate the red imported fire ant (Solenopsis invicta) from Brisbane. The invasion was deemed to be almost eradicated in 2004 but our analyses indicate that its geographic range continued to expand despite a sharp decline in number of nests. We also show that eradication would probably have been achieved with a relatively small increase in the area searched and treated. Our results demonstrate the importance of inferring temporal and spatial trends in ongoing invasions. The method can handle incomplete observations and takes into account the effects of human intervention. It has the potential to transform eradication practices.


Pulmonary-Renal Syndrome During COVID-19 Pandemic Revealed a Rare Case of Anti-GBM Disease.
Anti-GBM disease is a rare, life-threatening small vessel vasculitis caused by circulating anti-GBM antibodies resulting to rapidly progressive glomerulonephritis and/or pulmonary haemorrhage. The gold standard for the diagnosis is the renal biopsy with the pathognomonic finding of linear deposition of IgG along the glomerular capillaries. Early diagnosis and intervention are key determinants of the response to therapy and long-term prognosis of these patients. However, during COVID-19 pandemic recognizing a pulmonary-renal syndrome caused by autoimmune diseases has become challenging. Herein, we aimed to describe a rare case of anti-GBM disease with pulmonary haemorrhage and rapidly progressive glomerulonephritis in a young man in a tertiary referral hospital in Greece, while COVID-19 pandemic was at its peak. Although the patient presented high level of creatinine and crescents, the early diagnosis and start of treatment resulted to favourable renal prognosis.


[Plasma insulin and glucagon after ingestion of meal enriched with increased doses of pectin in healthy man].
The effects of three doses of pectin (5, 10 and 15 g) included in a solid-liquid meal on the postprandial plasma insulin and glucagon responses were studied in 12 healthy men. The mean plasma glucagon level was significantly smaller with 5 g of pectin than the control values at 150 min (p less than 0.05) whereas plasma insulin values did not vary. No change in mean plasma glucagon and insulin levels was noted with 10 g and 15 g of pectin although the mean blood glucose levels were significantly higher than the control values at 180 min (p less than 0.05). Addition of pectin to a meal, even if the doses were relatively important, had little or no effect on the postprandial hormonal responses in healthy men. However, pectin could be of renewed interest because of the possibility of its action of satiety by means of sustained late blood glucose levels.


A cognitive remediation training for young adults with psychotic disorders to support their participation in education - study protocol for a pilot randomized controlled trial.
Most severe mental disorders have their onset between the age of 17 and 27, a time when many young adults begin participating in secondary or post-secondary education. The cognitive deficits typically associated with psychiatric disorders, especially psychotic disorders, increase the risk of leaving school early, which can lead to a reduction in employment opportunities later on in life and, in turn, a poorer long-term prognosis. Therefore, specific interventions aiming to improve these cognitive functions are needed. Cognitive remediation (CR) aims to improve cognitive functioning and may increase real-world functioning in educational performance. This study aims to examine the feasibility and applicability of a CR training named Mindset for students with psychotic disorders in the Netherlands. Sixty students diagnosed with a psychotic disorder and currently reporting cognitive deficits will be included from four Dutch Mental Health Care institutes. Half of the participants (N = 30) will be randomly assigned to the CR training consisting of twelve, individual, weekly 1-h meetings. The other half will be assigned to an active control condition consisting of twelve weekly assignments that will be sent by email aiming to improve school performance. Students will be evaluated at baseline (T0), directly after finishing the CR training or control intervention (T1), and 6 months later (T2). Treatment feasibility will be the primary outcome, using evaluation forms, interviews with trainers and participants, number of study drop outs, and patient eligibility and recruitment rates. School functioning, cognitive functioning, and strategy use will also be assessed to get a preliminary idea of the potential effectiveness of the intervention. The CR training in this study will provide real-world examples and exercises aimed to teach useful strategies to cope with the cognitive deficits experienced by students with psychotic disorders. Furthermore, since students with other psychiatric disorders might also experience cognitive deficits, the results of this study may also provide some further implications for future studies on the effect of this CR training for students with these disorders. The study was registered with Trialregister.nl, no. NL6590 (NTR6764), date registered: September 7, 2017. Register name: Mindset. A cognitive rehabilitation training for young adults with psychotic spectrum disorder in an educational setting: A pilot study.Protocol version: 3, date December 23, 2019.


Viral protein Nef is detected in plasma of half of HIV-infected adults with undetectable plasma HIV RNA.
To address the role of translationally active HIV reservoir in chronic inflammation and non-AIDS related disorders, we first need a simple and accurate assay to evaluate viral protein expression in virally suppressed subjects. We optimized an HIV Nef enzyme-linked immunosorbent assay (ELISA) and used it to quantify plasma Nef levels as an indicator of the leaky HIV reservoir in an HIV-infected cohort. This study accessed 134 plasma samples from a well-characterized cohort study of HIV-infected and uninfected adults in San Francisco (the SCOPE cohort). We optimized an ELISA for detection of plasma Nef in HIV-negative subjects and HIV-infected non-controllers, and evaluated its utility to quantify plasma Nef levels in a cross-sectional study of ART-suppressed and elite controller HIV-infected subjects. Here, we describe the performance of an optimized HIV Nef ELISA. When we applied this assay to the study cohort we found that plasma Nef levels were correlated with plasma HIV RNA levels in untreated disease. However, we were able to detect Nef in plasma of approximately half of subjects on ART or with elite control, despite the lack of detectable plasma HIV RNA levels using standard assays. Plasma Nef levels were not consistently associated with CD4+ T-cell count, CD8+ T-cell count, self-reported nadir CD4+ T-cell count or the CD4+/CD8+ T-cell ratio in HIV-infected subjects. Since plasma HIV RNA levels are undetectable in virally suppressed subjects, it is reasonable to assume that viral protein expression in leaky reservoir, and not plasma virions, is the source of Nef accumulating in plasma. To examine this further, improvements of the assay sensitivity, by lowering the background through improvements in the quality of Nef antibodies, and detailed characterization of the HIV reservoirs are needed.


A Fusion Protein of the p53 Transaction Domain and the p53-Binding Domain of the Oncoprotein MdmX as an Efficient System for High-Throughput Screening of MdmX Inhibitors.
In nearly half of cancers, the anticancer activity of p53 protein is often impaired by the overexpressed oncoprotein Mdm2 and its homologue, MdmX, demanding efficient therapeutics to disrupt the aberrant p53-MdmX/Mdm2 interactions to restore the p53 activity. While many potent Mdm2-specific inhibitors have already undergone clinical investigations, searching for MdmX-specific inhibitors has become very attractive, requiring a more efficient screening strategy for evaluating potential scaffolds or leads. In this work, considering that the intrinsic fluorescence residue Trp23 in the p53 transaction domain (p53p) plays an important role in determining the p53-MdmX/Mdm2 interactions, we constructed a fusion protein to utilize this intrinsic fluorescence signal to monitor high-throughput screening of a compound library. The fusion protein was composed of the p53p followed by the N-terminal domain of MdmX (N-MdmX) through a flexible amino acid linker, while the whole fusion protein contained a sole intrinsic fluorescence probe. The fusion protein was then evaluated using fluorescence spectroscopy against model compounds. Our results revealed that the variation of the fluorescence signal was highly correlated with the concentration of the ligand within 65 μM. The fusion protein was further evaluated with respect to its feasibility for use in high-throughput screening using a model compound library, including controls. We found that the imidazo-indole scaffold was a bona fide scaffold for template-based design of MdmX inhibitors. Thus, the p53p-N-MdmX fusion protein we designed provides a convenient and efficient tool for high-throughput screening of new MdmX inhibitors. The strategy described in this work should be applicable for other protein targets to accelerate drug discovery.


Walking Kinematic Coordination Becomes More In-Phase at Extreme Inclines.
Previous research has shown that there are differences in mechanical energy, kinematics, and muscle activation when comparing walking on level and incline surfaces, especially on inclines above 15%. Muscle activations are significantly different while walking on extreme inclines, suggesting a different coordination pattern. We utilized continuous relative phase to assess walking kinematic coordination with respect to increased incline angles. Twelve healthy, college-aged individuals walked for 7 inclines of 1 minute each on a motorized treadmill at 3 mph at 0%, 5%, 10%, 15%, 20%, 25%, and 30% inclines. Kinematic data were collected during the last 20 seconds of each stage (120 Hz). Segmental and joint angles and angular velocities in the sagittal plane were calculated, from which continuous relative phase was determined for 3 joint couples: hip-knee, hip-ankle, and knee-ankle. There were significant differences in the coordination patterns during the first part of the contact phase in the hip-knee and hip-ankle couplings between the 0% and 30% inclines, with all 3 joint couplings becoming more in-phase at inclines above 15%. Importantly, the hip-knee coupling changed significantly from more out-of-phase to more in-phase between 10% and 15% incline. Shifting lower-extremity joint coordination in response to extreme inclines identifies potential coordinative strategies to achieve steep walking.


Changes in the vitamin D endocrine system and bone turnover after oral vitamin D3 supplementation in healthy adults: results of a randomised trial.
There is uncertainty as to which intake of vitamin D is needed to suppress PTH and maintain normal bone metabolism throughout winter at northern latitudes. We aimed to investigate whether four weeks' daily supplementation with 10 μg vitamin D3 from fish oil produced a greater change in serum vitamin D metabolites, parathyroid hormone, and bone turnover in healthy adults compared with solid multivitamin tablets. Furthermore, it was studied whether age, gender, ethnic background, body mass index, or serum concentrations at baseline predicted the magnitude of change in these parameters. Healthy adults aged 19-48 years living in Oslo, Norway (59°N) were randomised to receive a daily dose of 10 μg vitamin D3 given as fish oil capsules or multivitamin tablets during four weeks in late winter. Serum samples from baseline and after 28 days were analysed for 25-hydroxyvitamin D (s-25(OH)D), 1,25-dihydroxyvitamin D (s-1,25(OH)2D), intact parathyroid hormone (s-iPTH), and osteoclast-specific tartrate-resistant acid phosphatase 5b (s-TRACP). Fifty-five eligible participants completed the intervention (74% of those randomised). S-25(OH)D increased by mean 34.1 (SD 13.1) nmol/l, p < 0.001; s-iPTH decreased by mean 1.2 (SD 2.5) pmol/l, p = 0.001; s-1,25(OH)2D increased by mean 13 (SD 48) pmol/l, p = 0.057; and s-TRACP increased by mean 0.38 (SD 0.33) U/l, p < 0.001. For all these parameters, there was no difference between fish oil and multivitamin formulation. Baseline concentrations were the only independent predictors of changes in biochemical parameters. Four weeks of daily supplementation with 10 μg vitamin D3 decreased mean s-iPTH and increased s-TRACP concentration, and this did not differ by mode of administration. Our results suggest an increased bone resorption following vitamin D supplementation in young individuals, despite a decrease in parathyroid hormone levels. ClinicalTrials.gov: NCT01482689.


[An online tool to personalize the drug-doses for obese adults].
Between 1975 and 2014, the number of people suffering from obesity tripled, reaching 17% of the adult population in France and more than 35% in the United States. Obesity is defined by a Body Mass Index (BMI)>30kg/m2 and characterized by a significant accumulation of adipose tissue responsible for the increase in weight. This accumulation leads to physiological changes capable of modifying the pharmacokinetics of drugs, which can lead to the administration of inappropriate doses. For this reason, some significant dosage adjustments are necessary for obese patients. However, data on these adaptations are not easily accessible and sometimes complex to implement in practice. To perform a new online tool allowing to calculate and propose an adjusted dose of a drug that should be administered to an obese patient. (i) carrying out an extensive bibliographic research according to the PRISMA methodology; and (ii) the development of a new website site proposing an adjusted dose for obese patients. Firstly, 49 reviews concerning the dose adaptation have been evaluated and, secondly, 319 articles have been selected. Among them, 204 articles have been included in the database to justify the adjusted dose of 84 drugs and administration methods including antibiotics, antifungals, anticoagulants or even cancer drugs. This database is available online through a calculator on the website named Adapt'Obese. Thus, with the sex, height and weight of an obese patient, Adapt'Obese proposes a personalized and adjusted dose of the drug to administer. Other drugs will be added soon, and functional improvements are planned, with the aim of adapting the dosages in obese patients, as for patients with renal insufficiency.


Biloma and biliary fistula associated with hepatorrhaphy for liver injury.
To review our experience in managing post-hepatorrhaphy complications in liver trauma. During the period of 1986-1994, 6250 trauma patients were admitted to the Accident & Emergency Unit of the University Hospital Kuala Lumpur. The medical records were reviewed. There were 175 patients with liver trauma requiring hepatorrhaphy. The major post-operative complications (biloma and biliary fistula) were noted. We reviewed and discussed the various management of these biliary complications. Eleven patients developed either a biloma, biliary fistula or both. Patients age ranged from 15 to 40 years with a mean ISS of 23. Seven patients suffered penetrating injury and 4 were victims of blunt trauma. The right lobe was injured in 10 patients, with 1 patient sustaining left lobe injury. All liver injuries were either grade 3 (7 patients) or grade 4 (4 patients). No patient sustained extrahepatic biliary tract injury. Biloma and fistulas were diagnosed 14-30 days post-injury (mean 24 days) by CT or HIDA scans. All were managed by CT-guided percutaneous drainage. One patient also required percutaneous transhepatic cholangiography with biliary stent placement due to bile-stained ascites. Fistulas persisted from 5-120 days (mean 44 days). No patient required further operative intervention all fistula closed spontaneously without complication. Uncomplicated biliary fistula post-hepatectomy for liver trauma can be treated with percutaneous drainage.


Botryoid rhabdomyosarcoma of the biliary tract in children: a unique case report.
Rhabdomyosarcoma (RMS) is the most common tumour of the biliary tree in childhood. In children, it is a rare lesion, accounting for about 1% of all RMS. Hepatobiliary botryoid RMS is a disease affecting young children at a median age of about 3 years. In literature, the radiological findings of hepatobiliary RMS have been described in small series and some case reports. In this case report, we present a rare case of RMS of the extrahepatic biliary tree initially diagnosed as a choledochal cyst.


Functional Modulation of Voltage-Gated Sodium Channels by a FGF14-Based Peptidomimetic.
Protein-protein interactions (PPI) offer unexploited opportunities for CNS drug discovery and neurochemical probe development. Here, we present ZL181, a novel peptidomimetic targeting the PPI interface of the voltage-gated Na+ channel Nav1.6 and its regulatory protein fibroblast growth factor 14 (FGF14). ZL181 binds to FGF14 and inhibits its interaction with the Nav1.6 channel C-tail. In HEK-Nav1.6 expressing cells, ZL181 acts synergistically with FGF14 to suppress Nav1.6 current density and to slow kinetics of fast inactivation, but antagonizes FGF14 modulation of steady-state inactivation that is regulated by the N-terminal tail of the protein. In medium spiny neurons in the nucleus accumbens, ZL181 suppresses excitability by a mechanism that is dependent upon expression of FGF14 and is consistent with a state-dependent inhibition of FGF14. Overall, ZL181 and derivatives could lay the ground for developing allosteric modulators of Nav channels that are of interest for a broad range of CNS disorders.


[Arterial hypertension: current large therapeutic trials].
In this review, the design and objectives of ongoing clinical trials in essential hypertension are discussed along with the main results obtained from previously published therapeutic trials. In a meta-analysis of 14 of the major primary prevention trials in hypertension, the difference in diastolic blood pressure between the intervention groups and the control groups was only 5-6 mmHg. This difference was associated with significant reductions in all stroke events (42 per cent), all coronary heart disease events (14 per cent) and in cardiovascular mortality (21 per cent). In elderly hypertensive patients, available studies have shown that antihypertensive treatment reduces the incidence of non-fatal cardiovascular events without significantly modifying cardiovascular mortality. Most of these results were obtained with beta-blockers or diuretics. Despite official recommendation as first line monotherapy, none of the three new antihypertensive classes has been shown to have beneficial effects on hard primary endpoints such as cardiovascular morbidity and mortality. Several ongoing large scale randomized controlled trials vs. beta-blockers or diuretics are addressing this important issue. Moreover, other effects of antihypertensive treatment such as the 'J-curve phenomenon', the rate of change in the carotid wall thickness or the exact beneficial effects in elderly patients are being investigated in some of these studies.


The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias.
Polyglutamine (polyQ) spinocerebellar ataxias (SCAs) are the most prevalent subset of SCAs and share the aberrant expansion of Q-encoding CAG repeats within the coding sequences of disease-responsible genes as their common genetic cause. These polyQ SCAs (SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17) are inherited neurodegenerative diseases characterized by the progressive atrophy of the cerebellum and connected regions of the nervous system, which leads to loss of fine muscle movement coordination. Upon the expansion of polyQ repeats, the mutated proteins typically accumulate disproportionately in the neuronal nucleus, where they sequester various target molecules, including transcription factors and other nuclear proteins. However, it is not yet clearly understood how CAG repeat expansion takes place or how expanded polyQ proteins accumulate in the nucleus. In this article, we review the current knowledge on the molecular and cellular bases of nuclear proteotoxicity of polyQ proteins in SCAs and present our perspectives on the remaining issues surrounding these diseases.


Development and validation of a method for simultaneous analysis of the boar taint compounds indole, skatole and androstenone in pig fat using liquid chromatography-multiple mass spectrometry.
Boar taint in entire male pigs remains a problem for fresh pork production. Since castration of pigs will be prohibited in the future on animal welfare reasons, attempts are made to detect boar taint pre and post mortem. Post mortem techniques focus on simultaneous quantification of the three boar taint substances by one simple and reliable method. In this study a liquid chromatographic multiple mass spectrometric (LC-MS(n)) method has been developed and validated for the simultaneous determination of indole (2,3-benzopyrrole, ID), skatole (3-methylindole, SK) and androstenone (5alpha-androst-16-en-3-one, AEON) in pig fat samples. Sample preparation was kept as short as possible, since a single extraction method for structurally different indols and steroids was seeked after. Analytes were extracted from the fat matrix by methanol and clean-up consisted of freezing the extract in liquid nitrogen followed by a filtration step. The analytes were chromatographically separated on a Symmetry C(18) column. Recoveries for ID, SK and AEON, as calculated from fortified fat samples using 2-methylindole (2-MID) as internal standard, were 96, 91 and 104%, respectively. However, matrix interferences were encountered determining the androstenone levels in fat. Linearity, determined in fat samples, was in the range of 50-1600 microg kg(-1) for the indolic compounds and 125-2000 microg kg(-1) for the steroid AEON. The correlation coefficients (R(2)) of the calibration curves were 0.998 for ID, 0.997 for SK and 0.810 for AEON.


Quest for Quality Prize.
North Mississippi Medical Center, Tupelo, received this year's American Hospital Asso ciation McKesson Quest for Quality Prize, which recognizes leadership and innovation in quality, safety and commitment to patient care. Finalists were El Camino Hospital, Mountain View, Calif., and New York-Presbyterian Hospital, New York City.


Corticostatic peptides cause nifedipine-sensitive volume reduction in jejunal villus enterocytes.
We studied cell-volume changes caused by adding corticostatin (CS) or defensin-like peptides to villus enterocytes isolated in suspension from guinea pig jejunum. Guinea pig CS (10(-9) M) added to villus cells in Na(+)-containing medium reduced volume, but immediate cell swelling was caused by 10(-6) M guinea pig CS. In Na(+)-free N-methyl-D-glucamine-containing medium 10(-9) M guinea pig CS accelerated the initial rate of shrinkage compared with cells in N-methyl-D-glucamine-containing medium alone as well as causing greater cell shrinkage. Guinea pig CS-stimulated cell shrinkage was prevented by a Ca2(+)-channel blocker--5 microM nifedipine, by chelation of extracellular Ca2+ with 100 microM EGTA, or by omega-conotoxin (10(-9) M). The Ca2+ ionophore A23187 (2.5 microM) reduced volume when added to villus cells in N-methyl-D-glucamine-containing medium; this action was prevented by EGTA, or quinine--an inhibitor of K+ conductance, or 9-anthracenecarboxylic acid--a Cl- channel blocker, suggesting that the volume reduction occurred because K+ and Cl- conductances were activated. Guinea pig CS-stimulated volume reduction was also prevented by 100 microM quinine or 9-anthracenecarboxylic acid. We conclude that jejunal villus enterocytes possess a Ca2(+)-activated Cl- conductance and a K+ conductance that need not be stretch-activated. Corticostatic peptides cause volume reduction in villus cells by activating L-type Ca2+ channels; other defensin-like peptides were without effect.


Amphiphilic NO-donor antioxidants.
Models of amphiphilic NO-donor antioxidants 24-26 were designed and synthesized. The products were obtained by linking a lipophilic tail (C(6), C(8), C(10)) with a polar head constituted by the 2,6-dimethoxyphenol antioxidant joined to the NO-donor 3-furoxancarboxamide substructure through a bridge containing a quaternary ammonium group. Compound 23, containing the shortest C(2)-alkyl chain, was also studied as a reference. The antioxidant properties (TBARS and LDL oxidation assays) and the vasodilator properties of the compounds were studied in vitro. The ability of these products to interact with phospholipid vesicles was also investigated by NMR techniques. The results indicate that both activities are modulated by the ability of the compounds to accumulate on phospholipid layers.


Oct-1 binds promoter elements required for transcription of the GnRH gene.
The GnRH gene is exclusively expressed in a discrete population of neurons in the hypothalamus. The promoter-proximal 173 bp of the rat GnRH gene are highly conserved through evolution and are bound by multiple nuclear proteins found in the neuronal cell line, GT1-7, a model for the GnRH-expressing hypothalamic neuron. To explore the protein-DNA interactions that occur within this promoter and the role of these interactions in targeting GnRH gene expression, we have mutagenized individual binding sites in this region. Deoxyribonuclease I protection experiments reveal that footprint 2, a 51-bp sequence that confers a 20-fold induction of the GnRH gene, is comprised of at least three independent protein-binding sites. Transfections of the GnRH promoter-reporter plasmid containing a series of block mutations of footprint 2 into GT1-7 neurons indicate that each of the three putative component sites contributes to transcriptional activity. Mutations in footprint 4 also decrease GnRH gene expression. Footprint 4 and the promoter-proximal site in footprint 2 contain octamer-like motifs, an element that is also present in the neuron-specific enhancer of the rat GnRH gene located approximately 1.6 kb upstream of the promoter. Previous studies in our laboratory have demonstrated that two enhancer octamer sites are bound by the POU-homeodomain transcription factor Oct-1 in GT1-7 cells. We now show that Oct-1 binds the octamer motifs within footprints 2 and 4. Thus, Oct-1 plays a critical role in the regulation of GnRH transcription, binding functional elements in both the distal enhancer and the promoter-proximal conserved region.


New recognition of the natural history and growth pattern of hepatic hemangioma in adults.
Surgical indications for hepatic hemangiomas are still not clearly defined due to limited data on their natural history. This study aimed to investigate the natural history and growth pattern of hepatic hemangiomas in adults. From April 2010 to March 2013, adult patients with hepatic hemangioma who had no prior treatment were enrolled. A routine follow up was performed to observe the natural history of the lesions and their tendency to cause complications. A total of 236 patients were enrolled in the study. The median size of hemangiomas was 4.5 cm (range, 0.6-19.2). During a median follow-up period of 48 months (range, 3-266), 61.0% patients had hemangiomas that increased in size, 23.7% patients had stable lesions and 8.5% patients had hemangiomas that decreased in size. The peak growth period of hemangiomas was in patients of less than 30 years of age (0.46 ± 0.41 cm/year) and the growth rate decreased significantly after 50 years of age (0.21 ± 0.40 cm/year). Hemangiomas of less than 2 cm had the lowest growth rate (0.16 ± 0.42 cm/year). The peak growth rate of hemangioma size was 8-10 cm (0.80 ± 0.62 cm/year), then decreased rapidly to 0.47 ± 0.91 cm/year while the hemangiomas were of more than 10 cm. Only nine patients had severe symptoms caused by hemangioma. No patients presented with hemangioma-related complications. The majority of hepatic hemangiomas have the tendency to increase in size but rarely cause complications. All the hemangiomas can be safely managed by observation, and surgery is only considered for patients with severe complications.


Diverse early dwarf mistletoes (Arceuthobium), ecological keystones of the Eocene Baltic amber biota.
Extant dwarf mistletoes (Arceuthobium M. Bieb., Viscaceae) are hemiparasites with complex roles in nature. They are one of the most severe pests in northern hemisphere conifer forests, but they also enhance the structural complexity and species diversity of the forests. Here, we describe the first pre-Miocene macrofossils of dwarf mistletoes. The fossils from Eocene Baltic amber provide new insights into the morphological evolution of the Arceuthobium lineage and its paleobiogeography. The amber inclusions were investigated with light microscopy and compared with extant Viscaceae and to historic descriptions of lost Baltic amber fossils with affinities to Viscaceae. Six fossil species of the Arceuthobium lineage, A. johnianum comb. nov., A. mengeanum comb. nov., A. conwentzii sp. nov., A. groehnii sp. nov., A. viscoides comb. nov. and A. obovatum sp. nov., occurred in source forests of Baltic amber, representing the oldest macrofossil evidence of dwarf mistletoes. They share morphological features of their bracts, internodes, fruits, and stomata with extant Arceuthobium. Differences from extant dwarf mistletoes, such as the perianth merosity, the nonfusion of squamate bracts and presence of oblanceolate expanded leaves, indicate their affiliation to an ancient lineage of the genus. The occurrence of six species of dwarf mistletoes in a single amber deposit suggests Arceuthobium was a keystone taxon of the Baltic amber source area. As in extant conifer forests, they probably influenced the structural complexity of the forest, not only leading to more open woodlands but also increasing species diversity, at least at a microhabitat scale.


Results of Biliary Reconstruction Using a Polytetrafluoroethylene Graft in Liver Transplant Patients.
Biliary complications after liver transplant are a major concern with their high incidence, the need for repeated and long-term treatment, and their potential effects on graft and patient survival. We report our experience with biliary anastomosis using a spiral polytetrafluoroethylene graft. Between December 8, 1988, and July 2016, we performed 538 liver transplant procedures. We used a spiral polytetrafluoroethylene graft for biliary anastomosis in 10 patients: for biliary stricture reconstruction after liver transplant in 4 patients and during the primary liver transplant in 6 patients. Four patients who underwent biliary stricture reconstruction are doing well, with normal liver function. Of the 6 patients who received the graft during primary liver transplant, 2 died from sepsis, although they maintained normal liver function. Of the 4 living patients, 1 had a biliary complication that was reconstructed surgically. The 4 living patients are currently doing well, with normal liver function. Our small series of patients shows that the use of a spiral polytetrafluoroethylene graft is effective at reducing biliary complications in transplant patients.


[Adjuvant treatment of breast cancer. Endocrine therapy].
For women with steroid receptor-positive breast cancers, endocrine therapy has proven to be a major component of adjuvant therapy reducing the risk of recurrence and death. The selective estrogen-receptor modulator (SERM) tamoxifen has been well established as safe and effective in the adjuvant care of both pre- and postmenopausal women. For premenopausal women, ovarian suppression is an important option to be considered. Additionally, aromatase inhibitors have recently demonstrated further benefits in postmenopausal women. The ideal sequencing of treatment with tamoxifen and/or an aromatase inhibitor is the subject of several ongoing studies.


Structure-activity relationship of reversible cholinesterase inhibitors: activation, channel blockade and stereospecificity of the nicotinic acetylcholine receptor-ion channel complex.
1. We have shown that all cholinesterase (ChE) inhibitors, in addition to their well-known anti-ChE activity, have multiple effects on the nicotinic acetylcholine receptor-ion channel (AChR) macromolecule resulting from interactions with the agonist recognition site and with sites located at the ion channel component. Activation, competitive antagonism and different types of noncompetitive blockade occurring at similar concentration ranges and contributing in different proportions result in complex and somewhat unpredictable alterations in AChR function. The question is now raised as to how each effect of these compounds contributes to their antidotal property against organophosphorus (OP) poisoning, and what set of actions makes one reversible ChE inhibitor a better antidote. Many lines of evidence support the importance of direct interactions with various sites on the AChR: 1) morphological and toxicological studies with (+) physostigmine showed that anti-ChE activity is not essential to protect animals against toxicity by irreversible ChE inhibitors; 2) (-)physostigmine is far more effective against OP poisoning; 3) open channel blockers such as mecamylamine with no significant anti-ChE activity enhance the protective action of (-)physostigmine; 4) neostigmine, pyridostigmine, (-)physostigmine and (+)physostigmine showed qualitatively and quantitatively distinct toxicity and damage to endplate morphology and function. 2. In prophylaxis and during the very early phase of OP poisoning, carbamates, especially (-)physostigmine combined with mecamylamine and atropine, could protect almost 100% of the animals exposed to multiple lethal doses of OPs. Electrophysiological data showed that (-)physostigmine, among several reversible ChE inhibitors, showed greater potency in depressing both endplate current (EPC) peak amplitude and tau EPC. Therefore, concerning neuromuscular transmission, it seems that the higher the potency of a drug in reducing endplate permeability, the better is its protection against OP toxicity. A reversible open channel blockade combined with some agonist property helps to decrease the effect of ACh at its agonist site and to reduce the ion permeability of open channels. It should be pointed out that, during the later phase of OP poisoning, AChR desensitization should be most prevalent. Thus, a drug that can remove the AChR from this rather irreversible state to a more reversible blocked state should be a better protector. Indeed, oximes such as 2-PAM and a more potent analog, HI-6, produce multiple alterations in AChR function that comprise increased channel activation and open-channel blockade.(ABSTRACT TRUNCATED AT 400 WORDS)


Bioguided fractionation of procyanidin B2 as potent anti coxsackie virus B and Herpes simplex from cypress (Cupressus sempervirens L.).
The methanolic extracts of cypress (Cupressus sempervirens L.) collected at three phenological stages were evaluated for their cytotoxicity on Vero cells by MTT test as well as on Herpes simplex (HSV-2) and coxsackie (CVB-3) viruses by plaque reduction assay. The methanolic extract exhibited the highest cytotoxicity against HSV-2 (IC50 = 20.40 µg/mL) and CVB-3 (IC50 = 47.50 µg/mL) at the flowering stage. This extract also exhibited a virucidal action both during the entry of viruses and the release of newly formed virions. The methanolic extract bioguided purification showed that the ethyl-acetate fraction was responsible for virucidal activity. This fraction was endowed with more important selectivity index of 8.15 for HSV-2 and 4.40 for CVB-3. The ethyl acetate fraction was subjected to thin layer chromatography fractionation and identification by HPLC-DAD-ESI-MSn. Results showed that the condensed tannin procyanidin B2 was identified for the first time responsible of the antiviral activity of cypress.


Citrus limonoids: analysis, bioactivity, and biomedical prospects.
Limonoids are a prominent group of secondary metabolites in citrus fruit. The bitter character of some compounds in this group has historically compromised the quality of citrus fruit and juice. Detecting bitter limonoids in citrus, understanding their origins, and developing methods for their removal from citrus juices have provided the basis for citrus limonoid research. Evaluation of the biological activity of citrus limonoids has indicated the potential of these compounds to improve human health as anticancer, cholesterol-lowering, and antiviral agents. This review chronicles the evolution of citrus limonoid research from defining their participation in citrus bitterness to their potential utilization as important contributors to improving human health and well-being.


[Clinical evaluation of biapenem (L-627) in children].
Biapenem (L-627) was evaluated for its efficacy and safety. The following results were obtained. L-627 was given to 9 patients with infections: 3 with pneumonia, 1 with acute bronchopneumonia, 1 with acute bronchitis, 1 with bacteremia, 1 with tonsillitis, 2 with exceptional case. Therapeutic responses were excellent in 3, good in 4, with an efficacy rate of 100%. Adverse reactions were noted. No abnormalities were shown in laboratory data. It has been concluded that L-627 is a useful drug for the treatment of bacterial infections in children.


Molecular characterisation of colour formation in the prawn Fenneropenaeus merguiensis.
Body colouration in animals can have a range of functions, with predator protection an important aspect of colour in crustaceans. Colour determination is associated with the carotenoid astaxanthin, which is taken up through the diet and stabilised in the tissues by the protein crustacyanin. As a variety of genes are found to play a role in colour formation in other systems, a holistic approach was employed in this study to determine the factors involved in Fenneropenaeus merguiensis colouration. Full length F. merguiensis crustacyanin subunit A and C sequences were isolated. Crustacyanin subunit A and C were found in the F. merguiensis transcriptomes of the muscle/cuticle tissue, hepatopancreas, eye stalk and nervous system, using 454 next generation sequencing technology. Custom microarray analysis of albino, light and dark F. merguiensis cuticle tissue showed genes encoding actin, sarcoplasmic calcium-binding protein and arginine kinase to be 4-fold or greater differentially expressed (p<0.05) and down-regulated in albinos when compared to light and dark samples. QPCR expression analysis of crustacyanin and total astaxanthin pigment extraction revealed significantly (p<0.05) lower crustacyanin subunit A and C gene transcript copy numbers and total astaxanthin levels in albinos than in the light and dark samples. Additionally, crustacyanin subunit A and C expression levels correlated positively with each other. This study identified gene products putatively involved in crustacean colouration, such as crustacyanin, sarcoplasmic calcium-binding protein and forms of actin, and investigated differences in gene expression and astaxanthin levels between albino, light and dark coloured prawns. These genes open a path to enhance our understanding of the biology and regulation of colour formation.


Gene expression signature discriminates sporadic from post-radiotherapy-induced thyroid tumors.
Both external and internal exposure to ionizing radiation are strong risk factors for the development of thyroid tumors. Until now, the diagnosis of radiation-induced thyroid tumors has been deduced from a network of arguments taken together with the individual history of radiation exposure. Neither the histological features nor the genetic alterations observed in these tumors have been shown to be specific fingerprints of an exposure to radiation. The aim of our work is to define ionizing radiation-related molecular specificities in a series of secondary thyroid tumors developed in the radiation field of patients treated by radiotherapy. To identify molecular markers that could represent a radiation-induction signature, we compared 25K microarray transcriptome profiles of a learning set of 28 thyroid tumors, which comprised 14 follicular thyroid adenomas (FTA) and 14 papillary thyroid carcinomas (PTC), either sporadic or consecutive to external radiotherapy in childhood. We identified a signature composed of 322 genes which discriminates radiation-induced tumors (FTA and PTC) from their sporadic counterparts. The robustness of this signature was further confirmed by blind case-by-case classification of an independent set of 29 tumors (16 FTA and 13 PTC). After the histology code break by the clinicians, 26/29 tumors were well classified regarding tumor etiology, 1 was undetermined, and 2 were misclassified. Our results help shed light on radiation-induced thyroid carcinogenesis, since specific molecular pathways are deregulated in radiation-induced tumors.


Acute circulatory deficiency due to endocrinal tumoral manipulation: the pinealoblastoma.
We rapport the case of a patient presenting intra-abdominal metastasis of a pinealoblastoma, via a ventriculo-peritoneal shunt, confirmed by an anatomo-pathologic exam. The patient presented an acute hydrocephalus secondary to DVP dysfunction. The surgical manipulation of this metastasis had caused an acute circulatory deficiency due to massive serotonin release. In this case we analyze pineal gland physiology and serotonin effect on different systems.


Total synthesis of ionomycin using ring-opening strategies.
[structure: see text] The total synthesis of the polyether antibiotic ionomycin, a calcium ionophore, is described. The synthesis demonstrates the utility of ring-opening methodologies as applied to the synthesis of polypropionate and deoxypolypropionate subunits, which are found in two of the four fragments in the synthesis.


Immune function during and after 60 min of moderate exercise wearing protective clothing.
As exercise while wearing protective clothing exacerbates body heat storage compared to exercise in the heat, and as exercise alters immune responses, it appeared worthwhile to examine immune and stress responses while wearing protective clothing during moderate exercise. Eight subjects completed two bouts of exercise at 45% Vo2(max) in a thermoneutral environment: once while wearing shorts only (Control trial, CON) and again while wearing protective clothing (PRO). Venous blood samples were taken to analyze TNF-alpha mRNA by RT-PCR in LPS stimulated blood, plasma catecholamines, and cortisol. Blood cell count was analyzed by flow cytometry. Rectal temperature (T(re)) was monitored continuously. Exercise with PRO resulted in significantly greater increases in T(re) (39.2 +/- 0.2 degrees C in PRO vs. 38.0 +/- 0.1 degrees C in CON) and plasma epinephrine and norepinephrine (+70% and 150%, respectively). Plasma cortisol increased only at the end of PRO exercise (+33%). Leukocyte and lymphocyte cell count was 14% and 18% higher, respectively, but there were no significant changes in T cytotoxic and NK cell counts compared to the CON trial. Only T helper lymphocyte count was lower (-29%). During both exercise trials, T helper lymphocytes were significantly decreased at the end of exercise and recovery. With or without protective clothing, exercise was associated with an inhibition of TNF- alpha expression in stimulated monocytes (approximately -50% at min 20 and 40, and approximately -30% at min 60). Protective clothing wearing induces significant thermal challenge during exercise. The inhibition of TNF-alpha appears to be mediated primarily by exercise and not the added thermal load associated with protective clothing.


Fast feature selection using a simple estimation of distribution algorithm: a case study on splice site prediction.
Feature subset selection is an important preprocessing step for classification. In biology, where structures or processes are described by a large number of features, the elimination of irrelevant and redundant information in a reasonable amount of time has a number of advantages. It enables the classification system to achieve good or even better solutions with a restricted subset of features, allows for a faster classification, and it helps the human expert focus on a relevant subset of features, hence providing useful biological knowledge. We present a heuristic method based on Estimation of Distribution Algorithms to select relevant subsets of features for splice site prediction in Arabidopsis thaliana. We show that this method performs a fast detection of relevant feature subsets using the technique of constrained feature subsets. Compared to the traditional greedy methods the gain in speed can be up to one order of magnitude, with results being comparable or even better than the greedy methods. This makes it a very practical solution for classification tasks that can be solved using a relatively small amount of discriminative features (or feature dependencies), but where the initial set of potential discriminative features is rather large.


Choosing the filter for catenary image enhancement method based on the non-subsampled contourlet transform.
The quality of image enhancement plays an important role in the catenary fault diagnosis system based on the image processing technique. It is necessary to enhance the low contrast image of catenary for better detecting the state of catenary part. The Non-subsampled Contourlet transform (NSCT) is the improved Contourlet transform (CT), which can effectively solve the problem of artifact phenomenon in the enhanced catenary image. Besides, choosing the enhancement function and the filter of the NSCT will directly influence the image enhancement effect. In this paper, the proposed method is implemented by combining the NSCT with the nonlinear enhancement function to enhance the catenary image. First, how to choose the filter of the NSCT is discussed. Second, the NSCT is used to decompose the image. Then, the chosen nonlinear enhancement function is used to process the decomposed coefficient of the NSCT. Finally, the NSCT is inversed to obtain the enhanced image. In this paper, we evaluate our algorithm using the lifting wavelet transform, retinex enhancement method, dark channel enhancement method, curvelet transform, and CT method as a comparison to enhance a group of randomly selected low contrast catenary images, respectively. The results of comparative experiments conducted show that the proposed method can effectively enhance the catenary image, the contrast of image is improved, the catenary parts are obvious, and the artifact phenomenon is effectively eliminated, where image details (edges, textures, or smooth areas) are also well preserved. Besides, the values (detail variance-background variance, signal-to-noise ratio, and edge preservation index) of measuring the image enhancement capacity are improved, while the mean squared error value is decreased when compared to the CT method. These indicate that the proposed method is an excellent catenary image enhancement approach.