Upregulation of myosin Va by Snail is involved in cancer cell migration and metastasis.
Cell migration, which involves acto-myosin dynamics, cell adhesion, membrane trafficking and signal transduction, is a prerequisite for cancer cell metastasis. Here, we report that an actin-dependent molecular motor, unconventional myosin Va, is involved in this process and implicated in cancer metastasis. The mRNA expression of myosin Va is increased in a number of highly metastatic cancer cell lines and metastatic colorectal cancer tissues. Suppressing the expression of myosin Va by lentivirus-based RNA interference in highly metastatic cancer cells impeded their migration and metastasis capabilities both in vitro and in vivo. In addition, the levels of myosin Va in cancer cell lines are positively correlated with the expression of Snail, a transcriptional repressor that triggers epithelial-mesenchymal transition. Repression or overexpression of Snail in cancer cells caused reduced or elevated levels of myosin Va, respectively. Furthermore, Snail can bind to an E-box of the myosin Va promoter and induce its activity, which indicates that Snail might act as a transcriptional activator. These data demonstrate an essential role of myosin Va in cancer cell migration and metastasis, and suggest a novel target for Snail in its regulation of cancer progression.


Porous metallic MoO2-supported MoS2 nanosheets for enhanced electrocatalytic activity in the hydrogen evolution reaction.
Advanced materials for electrocatalytic water splitting are central to renewable energy research. In this work, MoS2 nanosheets supported on porous metallic MoO2 (MoS2/MoO2) were produced by sulfuration treatments of porous and highly conductive MoO2 for the hydrogen evolution reaction. Porous MoO2 with one-dimensional channel-like structures was prepared by calcination at elevated temperatures using phosphomolybdic acid as the precursor and mesoporous silica (SBA-15) as the template, and the subsequent hydrothermal treatment in the presence of thioacetamide led to the transformation of the top layers to MoS2 forming MoS2/MoO2 composites. Electrochemical studies showed that the obtained composites exhibited excellent electrocatalytic activity for HER with an onset potential of -104 mV (vs. RHE), a large current density (10 mA cm(-2) at -0.24 V), a small Tafel slope of 76.1 mV dec(-1) and robust electrochemical durability. The performance might be ascribed to the high electrical conductivity and porous structures of MoO2 with one-dimensional channels of 3 to 4 nm in diameter that allowed for fast charge transport and collection.


Ubiquitin signalling in Drosophila innate immune responses.
Cells respond to invading pathogens and danger signals from the environment by adapting gene expression to meet the need for protective effector molecules. While this innate immune response is required for the cell and the organism to recover, excess immune activation may lead to loss of homeostasis, thereby promoting chronic inflammation and cancer progression. The molecular basis of innate immune defence is comprised of factors promoting survival and proliferation, such as cytokines, antimicrobial peptides, and anti-apoptotic proteins. As the molecular mechanisms regulating innate immune responses are conserved through evolution, the fruit fly Drosophila melanogaster serves as a convenient, affordable, and ethical model organism to enhance understanding of immune signalling. Fly immunity against bacterial infection is built up by both cellular and humoral responses, where the latter is regulated by the Imd and Toll pathways activating NF-κB transcription factors Relish, Dorsal, and Dif, as well as JNK activation and JAK/STAT signalling. As in mammals, the Drosophila innate immune signalling pathways are characterized by ubiquitination of signalling molecules followed by ubiquitin receptors binding to the ubiquitin chains, as well as by rapid changes in protein levels by ubiquitin-mediated targeted proteasomal and lysosomal degradation. In this review, we summarise the molecular signalling pathways regulating immune responses to pathogen infection in Drosophila, with a focus on ubiquitin-dependent control of innate immunity and inflammatory signalling.


Cell-penetrating peptides as a novel transdermal drug delivery system.
In the last decade, almost one-third of the newly discovered drugs approved by the US FDA were biomolecules and biologics. Effective delivery of therapeutic biomolecules to their target is a challenging issue. Innovations in drug delivery systems have improved the efficiency of many of new biopharmaceuticals. Designing of novel transdermal delivery systems has been one of the most important pharmaceutical innovations, which offers a number of advantages. The cell-penetrating peptides have been increasingly used to mediate delivery of bimolecular cargoes such as small molecules, small interfering RNA nucleotides, drug-loaded nanoparticles, proteins, and peptides, both in vitro and in vivo, without using any receptors and without causing any significant membrane damage. Among several different drug delivery routes, application of cell-penetrating peptides in the topical and transdermal delivery systems has recently garnered tremendous attention in both cosmeceutical and pharmaceutical research and industries. In this review, we discuss history of cell-penetrating peptides, cell-penetrating peptide/cargo complex formation, and their mechanisms of cell and skin transduction.


Imaging linear and circular polarization features in leaves with complete Mueller matrix polarimetry.
Spectropolarimetry of intact plant leaves allows to probe the molecular architecture of vegetation photosynthesis in a non-invasive and non-destructive way and, as such, can offer a wealth of physiological information. In addition to the molecular signals due to the photosynthetic machinery, the cell structure and its arrangement within a leaf can create and modify polarization signals. Using Mueller matrix polarimetry with rotating retarder modulation, we have visualized spatial variations in polarization in transmission around the chlorophyll a absorbance band from 650 nm to 710 nm. We show linear and circular polarization measurements of maple leaves and cultivated maize leaves and discuss the corresponding Mueller matrices and the Mueller matrix decompositions, which show distinct features in diattenuation, polarizance, retardance and depolarization. Importantly, while normal leaf tissue shows a typical split signal with both a negative and a positive peak in the induced fractional circular polarization and circular dichroism, the signals close to the veins only display a negative band. The results are similar to the negative band as reported earlier for single macrodomains. We discuss the possible role of the chloroplast orientation around the veins as a cause of this phenomenon. Systematic artefacts are ruled out as three independent measurements by different instruments gave similar results. These results provide better insight into circular polarization measurements on whole leaves and options for vegetation remote sensing using circular polarization.


[France, an attractive country for international clinical research: 2010 survey assessed by Leem (French association of pharmaceutical companies)].
In order to evaluate the attractiveness of France for conducting international clinical trials, a survey is performed every two years among pharmaceutical companies that are based in France or have affiliates in France. Twenty-nine companies (72% of the French market) including 10 newly participants, have participated in the current survey which included 328 international phase II and III clinical studies, 79 countries, 24,337 centres and 249,704 patients (included in 2008/2009). France (291 patients/million inhabitants) ranked among the best European recruiters in second position behind Scandinavia. Since 2008, protocols are still to be given the go-ahead by French Authorities (Afssaps and CPP) within 60 days, in accordance with European directive. The continuation of reduction in deadlines for hospital contracts is encouraging and highlights the positive effect of CeNGEPS. French state-of-art is well recognized in Oncology/Hematology and Orphan disease which could be an example to improve the competitiveness of France in other key therapeutic areas such as Alzheimer's disease and Immuno-Inflammation.


Hand-assisted laparoscopic donor nephrectomy versus standard laparoscopic donor nephrectomy: a comparison study in the canine model.
The aim of this study was to compare live donor nephrectomy by hand-assisted laparoscopy to standard laparoscopy in a canine model. Fourteen dogs underwent a left laparoscopic nephrectomy; a standard laparoscopic nephrectomy technique was utilized in seven dogs. In a second group of seven dogs, a hand-assisted laparoscopic technique was used with a Dexterity Pneumo Sleeve hand port. All nephrectomies were performed as "donor" nephrectomies, dividing the vessels last. Total blood loss, operative warm ischemia, time and organ retrieval times were assessed for each group. The average operative time was significantly shorter for hand-assisted laparoscopic donor nephrectomy (32 +/- 8 minutes vs. 61 +/- 8 minutes; p = .02) than for the standard technique. The average warm ischemia (86 +/- 24 seconds vs. 224 +/- 52 seconds; p = .03) and average organ delivery times (4 +/- 3 seconds vs. 45 +/- 9 seconds; p < .01) also were shorter using the hand-assisted laparoscopic technique. No significant differences in average blood loss were found between the two groups (9 +/- 2 cc vs. 6 +/- 1 cc; p = 0.16, NS). Good parenchymal, ureteral, and vascular preservation was achieved by both techniques. Hand-assisted laparoscopy permits shorter operating times and warm ischemia times than standard laparoscopy in a canine model of donor nephrectomy. Hand assistance makes donor laparoscopic nephrectomy technically easier and significantly quicker to perform. If hand-assisted laparoscopy donor nephrectomy is confirmed to be a rapid and safe technique for removing an intact organ, laparoscopic nephrectomy will be a more widely accepted technique among urologists who participate in living related donor kidney transplantation.


Evidence-based systematic review: Oropharyngeal dysphagia behavioral treatments. Part IV--impact of dysphagia treatment on individuals' postcancer treatments.
This evidence-based systematic review (EBSR) is part of a series of reviews investigating swallowing behavioral treatments for individuals with dysphagia. This EBSR focuses primarily on individuals with dysphagia postcancer treatments. The seven behavioral interventions under review included three postural interventions (side lying, chin tuck, and head rotation) and four swallowing maneuvers (effortful swallow, Mendelsohn, supraglottic swallow, and super-supraglottic swallow). We systematically searched the dysphagia literature from March 2007 to April 2008. Six studies that met the inclusion and exclusion criteria were evaluated for methodological quality and characterized by research stage. Effect sizes were calculated when possible. All studies included were considered exploratory, with quality-marker scores ranging from 1 to 4 out of 7 possible markers. Five studies examined one or more of the four swallowing maneuvers, and one study addressed the chin-tuck posture. No studies addressed side lying or head rotation. Currently, limited evidence exists from six studies showing the positive effects of behavioral swallowing interventions for populations with structural disorder. Because of the range of structural deficits resulting from cancers and their treatments, further research is needed that evaluates specific intervention effectiveness.


Synthesis of D- and L-phenylalanine derivatives by phenylalanine ammonia lyases: a multienzymatic cascade process.
The synthesis of substituted D-phenylalanines in high yield and excellent optical purity, starting from inexpensive cinnamic acids, has been achieved with a novel one-pot approach by coupling phenylalanine ammonia lyase (PAL) amination with a chemoenzymatic deracemization (based on stereoselective oxidation and nonselective reduction). A simple high-throughput solid-phase screening method has also been developed to identify PALs with higher rates of formation of non-natural D-phenylalanines. The best variants were exploited in the chemoenzymatic cascade, thus increasing the yield and ee value of the D-configured product. Furthermore, the system was extended to the preparation of those L-phenylalanines which are obtained with a low ee value using PAL amination.


Rhetorical intentionality attribution: its ontogenesis in ordinary conversation.
This paper addresses the assumption that the epistemological dichotomy between reality and its construction is an everyday rhetorical tool children and adults use in their explanations and arguments. Within a discursive psychology perspective, the phenomenon of attribution of rhetorical intentionality (AIR) is theoretically defined developing the notion of prepackaged interest attribution technique (Edwards & Potter, 1992). AIR consists in an explanation of others' discursive moves in terms of a rhetorical-argumentative activity; that is, in terms of a deliberate attempt aimed at construing and presenting reality as a function of the speaker's point of view, perspective and interests, in order to affect the listeners mental state (belief, knowledge, intention) or action. Theoretical links are made to the theory of mind paradigm in the study of intentionality attribution, particularly to the form of life approach which defines intentionality attribution in terms of language games. On this basis, the present study examines the structures and functions of AIR used by children and their parents in everyday conversation. Qualitative discourse analysis of transcripts of 22 dinner conversations from eight Italian families shows explicit and implicit AIR in children from three and a half to seven years of age. Moreover, parents attribute rhetorical intentionality to their children, contributing to their social construction as rhetorical speakers. AIR is used as a rhetorical strategy within disputes and argumentative contexts, often achieving topic closure. Results are discussed with reference to the ontological status of intentionalist talk.


Genetic variation and phylogenetic relationships of 22 porcine reproductive and respiratory syndrome virus (PRRSV) field strains based on sequence analysis of open reading frame 5.
Porcine reproductive and respiratory syndrome virus (PRRSV) strains from 13 states in the United States, Guatemala and Canada were used to compare the envelope glycoprotein gene (ORF 5) nucleotide and deduced amino acid sequences. The gene was the same size, 603 nt, for all the 22 field strains. These strains had 89-94% amino acid identity compared to reference strain VR 2332. A putative signal sequence and cleavage site between residues 31 and 32 was identified and three potential glycosylation sites were present on all but two strains. Hydrophobicity/hydrophilicity and surface probability analyses reveal a primary structure for the envelope glycoprotein (E protein) with six potential surface regions that could be antigenic sites. Similar E protein structural features are conserved for the prototype European PRRSV-Lelystad virus.


Peripheral ulcerative keratitis secondary to chronic Citrobacter koseri canaliculitis.
Citrobacter koseri is a rarely reported ocular pathogen. It may induce severe peripheral corneal inflammation and subsequent perforation by canaliculitis. Timely detection of the reservoir of this pathogen would halt its progression. The purpose of this study was to report a rare presentation of C. koseri chronic canaliculitis complicated with perforating peripheral ulcerative keratitis (PUK). A 71-year-old female who had several episodes of C. koseri conjunctivitis in the past 6 months was admitted to our infection ward under the impression of fever that was suspected to be related to urinary tract infection. She had concurrent copious mucopurulent discharge and blurred vision. Ocular examination disclosed hyperemic conjunctiva and an oval-shaped corneal infiltrate at 5-6 o'c periphery, which later rapidly progressed to PUK and corneal perforation. Despite aggressive treatment, the cornea continued to thin, and a second perforation occurred. After meticulous examination of the ocular adnexa, irrigation of inferior canaliculi revealed pustular discharge with profuse concretions indicating chronic canaliculitis. A cutaneous-lacrimal fistula was also found. Frequent antibiotic irrigation of the canaliculus finally halted the corneal melting and the cornea healed. Although rare, C. koseri may not only cause chronic canaliculitis but also induce peripheral corneal inflammation mimicking autoimmune-related PUK. Identification of C. koseri from conjunctival swab cultures should prompt the physicians to check chronic persistent canaliculus infections, which may help prevent rapidly progressive corneal inflammation and thus perforation. Management of C. koseri canaliculitis-induced PUK must also include antibiotic irrigation to eradicate canaliculitis infection at the reservoir and not just topical antibiotics.


The EURONIC Project: a European concerted action on information to parents and ethical decision-making in neonatal intensive care.
The paper presents the background, objectives and methods of a European concerted action project aimed at exploring the transmission of information to parents and the ethical decision-making process in neonatal intensive care from the perspective of health personnel, and in relation to the legal, cultural, social and ethical backgrounds of the various European countries. Eight countries are taking part in the project (France, Germany, Italy, Luxembourg, Spain, Sweden, The Netherlands and the United Kingdom), which is about to be extended also to Central and Eastern Europe (Estonia, Lithuania and Hungary). In each of them, the medical and nursing personnel of a number of randomly selected units will be interviewed through an anonymous, self-administered questionnaire. Information on the organisation and policies of the Units and on the national legislation will also be collected. The key features of the study lie in the multidisciplinary and international approach, the random selection of the sample as a guarantee of representativeness and lack of selection bias, the focus on the staff practices as well as on their attitudes and opinions.


Aberrant location of inhibitory synaptic marker proteins in the hippocampus of dystrophin-deficient mice: implications for cognitive impairment in duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a neuromuscular disease that arises from mutations in the dystrophin-encoding gene. Apart from muscle pathology, cognitive impairment, primarily of developmental origin, is also a significant component of the disorder. Convergent lines of evidence point to an important role for dystrophin in regulating the molecular machinery of central synapses. The clustering of neurotransmitter receptors at inhibitory synapses, thus impacting on synaptic transmission, is of particular significance. However, less is known about the role of dystrophin in influencing the precise expression patterns of proteins located within the pre- and postsynaptic elements of inhibitory synapses. To this end, we exploited molecular markers of inhibitory synapses, interneurons and dystrophin-deficient mouse models to explore the role of dystrophin in determining the stereotypical patterning of inhibitory connectivity within the cellular networks of the hippocampus CA1 region. In tissue from wild-type (WT) mice, immunoreactivity of neuroligin2 (NL2), an adhesion molecule expressed exclusively in postsynaptic elements of inhibitory synapses, and the vesicular GABA transporter (VGAT), a marker of GABAergic presynaptic elements, were predictably enriched in strata pyramidale and lacunosum moleculare. In acute contrast, NL2 and VGAT immunoreactivity was relatively evenly distributed across all CA1 layers in dystrophin-deficient mice. Similar changes were evident with the cannabinoid receptor 1, vesicular glutamate transporter 3, parvalbumin, somatostatin and the GABAA receptor alpha1 subunit. The data show that in the absence of dystrophin, there is a rearrangement of the molecular machinery, which underlies the precise spatio-temporal pattern of GABAergic synaptic transmission within the CA1 sub-field of the hippocampus.


Investigation of optimal display size for viewing T1-weighted MR images of the brain using a digital contrast-detail phantom.
We clarified the relationship between the display size of MRI images and observer performance using a digital contrast-detail (d-CD) phantom. The d-CD phantom was developed using Microsoft Visual Basic 2010 Express. It had a 512 × 512 matrix in size and a total of 100 holes, whose diameter increased stepwise from 4 to 40 pixels with a 4-pixel interval in the vertical direction; the contrast varied stepwise in the horizontal direction. The digital driving level (DDL) of the back-ground, the width of the DDL, and the contrast were adjustable. These parameters were determined on the basis of the actual T1-weighted magnetic resonance (MR) images of the brain. In this study, the DDL, width, and contrast were set to 85, 20, and 1, respectively. The observer performance study was performed for three different display sizes (30 cm × 30 cm as the enlarged size, 16 cm × 16 cm as the original size, and 10 cm × 10 cm as the reduced size) using a 2-megapixel color liquid crystal display monitor, and it was analyzed using Friedman and Wilcoxon statistical tests. The observer performances for the original display (p < 0.01) and the reduced display sizes (p < 0.01) were superior to that observed for the enlarged size, whereas there was no significant difference between the original display and reduced display sizes (p = 0.31). Evaluation with the digital phantom simulating MR imaging also revealed that the original and reduced display sizes were superior to the enlarged display size in observer performance. The d-CD phantom enables a short-term evaluation of observer performance and is useful in analyzing relation-ship between display size and observer performance.


Tyrosine hydroxylase immunoreactive neurons throughout the hypothalamus receive glutamate decarboxylase immunoreactive synapses: a double pre-embedding immunocytochemical study with particulate silver and HRP.
Silver-intensified gold (SIG) particles were used for light- and electron-microscopic immunocytochemical localization of neuronal antigens, and the SIG method was compared with related heavy-metal methods for the purpose of dual ultrastructural localization of neurotransmitter-related antigens. SIG immunostaining was combined with peroxidase immunostaining to allow simultaneous study of differentially labeled tyrosine hydroxylase and glutamate decarboxylase immunoreactive neurons in the medial hypothalamus. A number of electron-dense markers that might be of use in double immunostaining for light and electron microscopy were examined, either with a simple nitrocellulose dot-blot method or on Formvar-coated slot grids. Of these, silver-intensified 5 nm colloidal gold was the most effective. Silver intensification of colloidal silver and of peroxidase reaction product also showed promise for combined LM and EM double-immunolabeling studies. Since the silver-intensification procedure used here intensifies both gold and peroxidase, in experiments involving, double staining, the silver-intensified gold procedure should be used for the first antigen and nonintensified HRP for the second. Presumptive dopaminergic neurons containing the enzyme tyrosine hydroxylase were located throughout the hypothalamus with SIG immunostaining. In the same areas where frequent tyrosine hydroxylase immunoreactive neurons were found, many axons and bouton terminals were also found with antisera against GABA or against the GABA-synthesizing enzyme glutamate decarboxylase. Areas containing cells immunoreactive for tyrosine hydroxylase and stained with SIG and axons immunoreactive for glutamate decarboxylase and stained with peroxidase included the periventricular area (A14), the arcuate nucleus (A12), the dorsomedial hypothalamus/zona incerta area (A13), the posterior hypothalamus (A11), the medial paraventricular nucleus, and dorsal to the supraoptic nucleus, in addition to the preoptic area near the third ventricle and dorsally adjacent to the anterior commissure. For comparison, the SIG procedure was also used to stain dopaminergic neurons outside the hypothalamus in the substantia nigra and ventral tegmental area. Double immunocytochemical staining of two different neurotransmitter-related antigens allowed examination with both light and electron microscopy. By virtue of a large silver shell formed around the colloidal gold particle and its adsorbed immunoglobulin or protein A, cross-reactivity of the first set of immunoreagents stained with particulate silver and a second set stained with peroxidase could be reduced or eliminated.(ABSTRACT TRUNCATED AT 400 WORDS)


Effect of ovariectomy on the proliferative capacity of intrahepatic rat cholangiocytes.
We evaluated the effects of ovariectomy (OVX) and estrogen replacement treatment on cholangiocyte proliferation induced by bile duct ligation (BDL). BDL (2 weeks) was performed in ovariectomized rats and the proliferative and apoptotic activity compared with normal, with BDL control rats, and with BDL +/- OVX rats treated with 17-beta estradiol. OVX induced a significant (P < 0.01) reduction of bile duct mass in BDL rats. The reduction of bile duct mass induced by OVX was associated with a decreased expression of estrogen receptor (ER)-alpha (2.5-fold) and, mainly, ER-beta (35-fold). Proliferating cellular nuclear antigen (PCNA) expression in cholangiocytes was impaired by OVX, indicating depression of proliferation, whereas terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) and Fas positivity were markedly enhanced, indicating activation of Fas-mediated apoptosis. Administration of 17-beta estradiol during BDL in OVX rats induced a normalization of bile duct mass, ER expression, cholangiocyte proliferation, and apoptosis (Fas and TUNEL) in comparison with untreated BDL rats. Our findings support the role of endogenous estrogens in sustaining the enhanced proliferative and secretory activities of cholangiocytes in cholestasis. On the basis of these data, the hypothesis of an estrogenic functional deficiency in chronic cholestatic liver diseases should merit careful attention.


Solvation structure and dynamics of Ag+ in aqueous ammonia solutions: A molecular simulation study.
We present an ab initio-based force-field for silver ion interactions with water and ammonia. Compared to quantum calculations, our model allows for rather large-scale molecular dynamics simulations of silver solutions of aqueous ammonia. For a series of NH3:H2O ratios ranging from 1 to 20 mol. %, Ag+ ions were mainly found as octahedral [Ag(NH3)x(H2O)]6-x+ coordination complexes with preferential values of x ranging from 0 to 3. In the first coordination structure, water ↔ ammonia exchanges occur within a 1-3 ps time scale and, depending on the NH3 concentration, imply significant fluctuations of x covering the whole range from 0 to 6. Based on ns-scale molecular dynamics simulations, chemical potentials are derived for all Ag+ coordination species as functions of temperature and ammonia concentration. Moreover, we compare the diffusion constants of the [Ag(H2O)6]+ to [Ag(H2O)3(NH3)3]+ coordination complexes, based on the solutions of the corresponding ammonia content.


Concurrent multiple health risk behaviors among adolescents in Luangnamtha province, Lao PDR.
Multiple health risk behaviors (HRBs) among adolescents pose a threat to their health, including HIV/AIDS. Health risk behaviors such as alcohol use, smoking, substance use, and sexual risk behaviors among youth have been shown to co-occur with each others. The objectives of this study was to estimate the prevalence of single and concurrent health risk behaviors and to explore how health risk behavior is associated with socio-demographic factors and peers' behaviors. A cross sectional design was used to examine health risk behaviors of adolescents between the age 14 and 19 years living in the Luangnamtha province, Lao PDR. The study was conducted between June and August, 2008. An ordinal logistic regression model that simultaneously explored demographic factors and the influence of the behavior of peers on three categories of multiple HRBs (no risk, one risk, and two or more health risk behaviors) was performed. A total of 1360 respondents, 669 (49.1%) boys with mean age 16.7 ± 1.6 and 699 (50.9%) girls aged 16.1 ± 1.5 were recruited into the study. The majority reported two or fewer risk behaviors. However, multiple risk behaviors increased with age for both sexes. About 46.8% (n = 637) reported no risk, 39.3 percent (n = 535) reported one risk, 8.1 percent (n = 110) reported two risks, and 5.8 percent reported more than two health risk behaviors.The protective factors among boys were school attendance (OR = .53, CI = .33-.86), being Hmong and Yao ethnicity (OR = .48, CI-.26-.90), while being above the age of 15 (OR = 2.20, 95% CI = 1.33-3.60), Akha ethnicity (OR = 2.20, 95% CI = 1.04-4.61), peer's smoking (OR = 3.11, 95% CI = 2.1-4.6), and peer's drinking alcohol (OR = 1.88, 95% CI = 1.1-3.21) were significantly associated with the presence of multiple risk behaviors among boys.Having some education (OR = 0.17, 95% CI = 0.06-0.45), and being of Hmong and Yao ethnicity (OR = 0.38, 95% CI = 0.18-0.80) were factors that protected girls from multiple risk behaviors; while peer's drinking alcohol (OR = 2.55, 95% CI = 1.59-4.09) and peer's being sexually active (OR = 2.82, 95% CI = 1.65-4.8) were significantly associated with the presence of multiple risk behaviors among girls. There are sex, age and ethnic differences in the concurrent health risk behaviors. The influencing factors are adolescent's education and peer influence. Interventions should focus to encourage adolescents to complete the compulsory primary education as well as help them to establish friendships and follow peers with good behavior. Risk reduction messages need to take account of diverse multiple HRBs within the specific socio-cultural and gender specific context and target vulnerable adolescents such as ethnic minorities and less educated adolescents.


Early medical abortion: legal and medical developments in Australia.
Mifepristone is a safe, effective and relatively cheap drug that plays an important role in women's health care and is widely used for early medical abortion in many countries. The Therapeutic Goods Administration (TGA) can authorise mifepristone to be imported into and marketed in Australia. To date, no pharmaceutical company has applied to register mifepristone in Australia. The TGA can also permit medical practitioners to prescribe medicine that is not approved for marketing in Australia under the Authorised Prescribers scheme. The number of approvals for mifepristone has gradually increased, in spite of a complicated and protracted application process. Approval under the Authorised Prescribers scheme requires medical practitioners to comply with state or territory legislation. Abortion laws in Australia vary between jurisdictions, and in some states the law is unclear and confusing. The decriminalisation of abortion in all Australian jurisdictions would protect medical practitioners from criminal liability, promote the health interests of Australian women, and discourage the illegal importation of abortifacients that are being used without quality controls or medical supervision. The Victorian Abortion Law Reform Act 2008 is one legislative model for this.


Truncated inception net: COVID-19 outbreak screening using chest X-rays.
Since December 2019, the Coronavirus Disease (COVID-19) pandemic has caused world-wide turmoil in a short period of time, and the infection, caused by SARS-CoV-2, is spreading rapidly. AI-driven tools are used to identify Coronavirus outbreaks as well as forecast their nature of spread, where imaging techniques are widely used, such as CT scans and chest X-rays (CXRs). In this paper, motivated by the fact that X-ray imaging systems are more prevalent and cheaper than CT scan systems, a deep learning-based Convolutional Neural Network (CNN) model, which we call Truncated Inception Net, is proposed to screen COVID-19 positive CXRs from other non-COVID and/or healthy cases. To validate our proposal, six different types of datasets were employed by taking the following CXRs: COVID-19 positive, Pneumonia positive, Tuberculosis positive, and healthy cases into account. The proposed model achieved an accuracy of 99.96% (AUC of 1.0) in classifying COVID-19 positive cases from combined Pneumonia and healthy cases. Similarly, it achieved an accuracy of 99.92% (AUC of 0.99) in classifying COVID-19 positive cases from combined Pneumonia, Tuberculosis, and healthy CXRs. To the best of our knowledge, as of now, the achieved results outperform the existing AI-driven tools for screening COVID-19 using the acquired CXRs, and proves the viability of using the proposed Truncated Inception Net as a screening tool.


Studies on the production of enterotoxins by Bacillus cereus.
Evidence is presented for the existence of three distinct enterotoxins detected in concentrated cell-free culture filtrates of selected Bacillus cereus strains. The first was a product capable of stimulating the adenylate cyclase-cyclic-AMP system in intestinal epithelial cells and, possibly through this, causing fluid accumulation in ligated ileal sections ("loops") of young rabbits. This was elaborated by a strain isolated from an incident of diarrhoea and which caused diarrhoea in 6 of 10 monkey feedings. The second was tentatively identified as a factor which caused fluid accumulation in rabbit loops but not, apparently, through stimulation of the adenylate cyclase-cyclic-AMP system; this was elaborated by a strain isolated from raw rice which failed to produce symptoms in eight monkey feedings. Together, the behaviour of these two factors indicates that diarrhoea caused by B. cereus enterotoxin may be a cyclic-AMP-mediated event. The third, here referred to as "pyogenic toxin", caused severe tissue damage in the ileal mucosa and was elaborated by a strain isolated from a brain abscess. A factor produced by a strain isolated from an outbreak of vomiting which caused vomiting in 10 of 24 monkey feedings could bot be detected in tests reported here but appears to be a fourth enterotoxin type. Cytopathic effects in tissue cultures, suckling mouse tests, and assays of glycerol production by fat cells were not found to be of value in the detection of any of the enterotoxins.


Arsenate(V) removal from aqueous system by using modified incinerated sewage sludge ash (ISSA) as a novel adsorbent.
Adsorption methods have been widely used in wastewater treatment due to its high removal efficiency, easy operation and handling, economic efficiency and little secondary pollution to the environment. In this paper, a high-iron containing incineration sewage sludge ash (ISSA) was modified by combined acid leaching and precipitation processes to improve its adsorption capacity of As(V). The effects of pH, time, temperature and ionic strength on the adsorption of As(V) were investigated by batch adsorption experiments. The results indicated that iron (mainly present as hematite) in the ISSA was rearranged to Fe(SO4)OH. The modified ISSA showed an excellent adsorption potential for As(V) under acidic conditions and the adsorption capacity was around 9 times of the unmodified ISSA at pH 2-3. The adsorption process was fast during the first 2 h and reached an equilibrium at around 6 h. The Freundlich model could well fit the adsorption isotherm data, the presence of NO3- and Cl- had a negligible influence on the As(V) removal by the modified ISSA, while PO43- and SO42- could significantly suppress As(V) removal via competitive adsorption. After 3 cycles of regeneration, the modified ISSA still showed a satisfying adsorption capacity. As(V) was removed by the modified ISSA mainly through ligand exchange reaction with hydroxyl oxygen (OH-) to form inner-sphere complexes. Therefore, the modified ISSA can be a promising material for As(V) removal from wastewater in particular due to the waste recycling potential.


Helicobacter pylori arginase inhibits T cell proliferation and reduces the expression of the TCR zeta-chain (CD3zeta).
Helicobacter pylori infects approximately half the human population. The outcomes of the infection range from gastritis to gastric cancer and appear to be associated with the immunity to H. pylori. Patients developing nonatrophic gastritis present a Th1 response without developing protective immunity, suggesting that this bacterium may have mechanisms to evade the immune response of the host. Several H. pylori proteins can impair macrophage and T cell function in vitro through mechanisms that are poorly understood. We tested the effect of H. pylori extracts and live H. pylori on Jurkat cells and freshly isolated human normal T lymphocytes to identify possible mechanisms by which the bacteria might impair T cell function. Jurkat cells or activated T lymphocytes cultured with an H. pylori sonicate had a reduced proliferation that was not caused by T cell apoptosis or impairment in the early T cell signaling events. Instead, both the H. pylori sonicate and live H. pylori induced a decreased expression of the CD3zeta-chain of the TCR. Coculture of live H. pylori with T cells demonstrated that the wild-type strain, but not the arginase mutant rocF(-), depleted L-arginine and caused a decrease in CD3zeta expression. Furthermore, arginase inhibitors reversed these events. These results suggest that H. pylori arginase is not only important for urea production, but may also impair T cell function during infection.


Biocultural aspects of obesity in young Mexican schoolchildren.
Obesity related to over-nutrition is investigated in a sample of 219 Mexican children from affluent families, ages 6-12 years. Defined as weight-for-age at or above the 95(th) percentile, obesity rates in middle childhood are very high in this population, being 24.2% of children (29.4% of boys and 19.1% of girls). Binary logistic regression shows that children are more likely to be obese if they are boys, from small households with few or no other children, and have more permissive, less authoritarian parents. Diet at school and activity patterns, including television viewing, are not different for boys and girls and so do not explain this gender variation. The value placed on children, especially sons, in smaller middle-class families, can result in indulgent feeding because food treats are a cultural index of parental caring. Parents also value child fatness as a sign of health. These obese Mexican children have no greater social problems (peer rejection or stigma) or psychological problems (anxiety, depression, or low self esteem) than their non-obese peers. More study specifically focused on feeding practices in the home environment is required to explain very high rates of child obesity. The differences in obesity risk related to specific aspects of children's developmental microniche emphasize the importance of including a focus on gender as a socio-ecological construct in human biological studies of child growth, development, and nutrition.


Peptidoglycan of Staphylococcus aureus induces enhanced levels of matrix metalloproteinase-9 in human blood originating from neutrophils.
Enhanced plasma levels of matrix metalloproteinase 9 (MMP-9) detected in patients with severe sepsis are thought to contribute to the development of organ dysfunction in endotoxemia. We have recently reported that peptidoglycan, the major wall component of gram-positive bacteria, increases MMP-9 levels in lung and liver and organ injury in the rat. Thus far, it is unclear whether MMP-9 is part of the septic response to peptidoglycan in human blood. The aim of the present study was to examine the regulation of MMP-9 by peptidoglycan in human leukocytes. The addition of peptidoglycan to whole human blood caused enhanced levels of MMP-9 after 1 h of incubation (306 vs. 75 ng/mL, P < or = 0.05) and onward, as measured by enzyme-linked immunoabsorbant assay. In neutrophil cultures, MMP-9 values increased significantly after 30 min of incubation with peptidoglycan (242 vs. 121 ng/mL, P < or = 0.05), whereas muramyl dipeptide had no effect. In contrast, adherent monocytes released insignificant amounts of MMP-9. To examine whether the released MMP-9 resulted from de novo synthesis, intracellular and secreted MMP-9 was measured during stimulation of neutrophils. The total MMP-9 values (the sum of intracellular and secreted MMP-9) before and after stimulation were mainly unaltered. The enhanced MMP-9 levels induced by peptidoglycan was attenuated by inhibitors of p38 mitogen-activated protein kinases (MAPK), (SB202190, 25 microM) and ERK1/2 (PD98059, 25 microM) and inhibitors of Src Tyrosine kinase (PP2, 5 microM) and PI3-K (LY294002, 25 microM).


Changes in commitment to change among leaders in home help services.
The purpose of the this study was to explore the development of commitment to change among leaders in the home help services during organizational change and to study this development in relation to workload and stress. During organizational change initiatives, commitment to change among leaders is important to ensure the implementation of the change. However, little is known of development of commitment of change over time. The study used a qualitative design with semi-structured interviews with ten leaders by the time an organizational change initiative was launched and follow-up one year later. Thematic content analysis was used to analyze the interviews. Commitment to change is not static, but seems to develop over time and during organizational change. At the first interview, leaders had a varied pattern reflecting different dimensions of commitment to change. One year later, the differences between leaders' commitment to change was less obvious. Differences in commitment to change had no apparent relationship with workload or stress. The data were collected from one organization, and the number of participants were small which could affect the results on workload and stress in relation to commitment to change. It is important to support leaders during organizational change initiatives to maintain their commitment. One way to accomplish this is to use management team meetings to monitor how leaders perceive their situation. Qualitative, longitudinal and leader studies on commitment to change are all unusual, and taken together, this study shows new aspects of commitment.


Meta analysis of ovulation induction effect and pregnancy outcome of acupuncture & moxibustion combined with clomiphene in patients with polycystic ovary syndrome.
Using Mesh Meta Analysis to evaluate the efficacy of Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene for treating Polycystic Ovary Syndrome (PCOS), in order to provide evidence-based medical evidence for whether to recommend Acupuncture & Moxibustion or Combine western medicine to treat PCOS. Eight databases including The Cochrane Library, Pubmed, Embase, Web of Science, CNKI, Wanfang Date, VIP and CBM were searched by computer. The included research period is from the establishment of the database to May 2023, which concerned with randomized controlled trials involving Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene on ovulation induction and pregnancy outcome in patients with PCOS. The duration of the research paper is from 2016 to 2023.The inclusion criteria refer to the Rotterdam standards issued by the European Center for Human Reproduction and Embryology and the American Society of Reproductive Medicine in January 2003, or the Expert Consensus on the Diagnosis and Treatment of Polycystic Ovarian Syndrome by the Endocrinology Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association. Simultaneously exclude related diseases, repetitive literature, as well as literature with incomplete abstract information and no original data provided. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias included in the study, using Stata17.0 software for a mesh meta-analysis. Six randomized controlled trials were included, covering 1410 PCOS patients. Three interventions included Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene. Mesh Meta Analysis showed that in terms of improving ovulation rate, there was no statistical difference between Acupuncture & Moxibustion (A), Clomiphene (B), Clomiphene combined with Acupuncture & Moxibustion (C) (P>0.05).Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=0.15,95% CI (-0.51,0.80)], Acupuncture & Moxibustion (A) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.60,95% CI (0.97,2.23)], Clomiphene (B) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.45,95% CI (0.91,1.99)]. In terms of pregnancy outcome, the difference between the three intervention methods was statistically significant (P<0.05). Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=-0.80,95% CI (-1.84,0.23)], Acupuncture & Moxibustion (A) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=0.29,95% CI (-0.73,1.30)], and Clomiphene (B) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.09,95% CI (0.39,1.79)], The order of pregnancy rate from high to low is Acupuncture & Moxibustion combined with Clomiphene (C), Acupuncture & Moxibustion (A), Clomiphene (C).In terms of influencing endometrial thickness, the difference between the three intervention methods was statistically significant (P<0.05). Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=-0.84,95% CI (-1.87,0.19)], Acupuncture & Moxibustion (A) versus Acupuncture & Moxibustion combined with Clomiphene (C) [MD=0.26,95% CI (-1.01,1.53)], Clomiphene (B) versus Acupuncture & Moxibustion combined with Clomiphene (C) [MD=1.10,95% CI (0.36,1.84)], Acupuncture & Moxibustion combined with Clomiphene (C) has the best effect on improving endometrial thickness. In subgroup analysis, the effect of Acupuncture & Moxibustion treatment frequency on ovulation rate and pregnancy rate was not statistically significant. The combination of Acupuncture & Moxibustion, Electroacupuncture and warm Acupuncture & Moxibustion has no effect on the pregnancy rate, but the combination of Electroacupuncture and Clomiphene has the best effect on improving the ovulation rate. In the observation of adverse reactions, compared with clomiphene alone, Acupuncture & Moxibustion combined with Clomiphene can reduce the occurrence of Luteinized Unruptured Follicle Syndrome (LUFS) and Ovarian Hyperstimulation Syndrome (OHSS), and reduce the occurrence of physical adverse reactions such as nausea, vomiting, headache and dermatitis. Acupuncture & Moxibustion is effective in improving the ovulation promoting effect and pregnancy outcome of PCOS patients. The ovulation promoting effect of Acupuncture & Moxibustion or combined with Clomiphene is similar to that of Clomiphene alone, but Acupuncture & Moxibustion combined with Clomiphene has more advantages in improving the pregnancy rate of PCOS, and it also can reduce the adverse reactions of Clomiphene alone. Acupuncture & Moxibustion can be used as a recommended treatment for PCOS. More cases should also be included in the subgroup analysis to study the impact of Acupuncture & Moxibustion programs on clinical efficacy and further optimize the Acupuncture & Moxibustion treatment program. https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier (CRD42023433057).


Strategic approach to the globalization of sasang constitutional medicine.
The workshop on "Strategic Approach to the Globalization of Sasang Constitutional Medicine (SCM)" was held in the Korea Institute of Oriental Medicine (KIOM) on September 18, 2009. This workshop was designed to discuss and brainstorm the strategic approach to the globalization of SCM, one of the unique systems in Korean Traditional Medicine, with three topics and an extensive panel discussion. Professor Edwin Cooper, Editor-in-Chief of eCAM, gave a commemorative lecture for publication of the second supplement of eCAM entitled "Sasang Constitutional Medicine as a Holistic Tailored Medicine". The other two presenters suggested some practical methods for globalization of SCM on the basis of their experiences. After the three main presentations, there was a panel discussion session for further development of workshop topics, extended by five other external experts. They discussed the benefits, limitations and essentials for globalization of Korean Traditional Medicine, specifically SCM, from bench to bedside.


Gas chromatographic quantification of fatty acid methyl esters: flame ionization detection vs. electron impact mass spectrometry.
The determination of FAME by GC is among the most commonplace analyses in lipid research. Quantification of FAME by GC with FID has been effectively performed for some time, whereas detection with MS has been used chiefly for qualitative analysis of FAME. Nonetheless, the sensitivity and selectivity of MS methods advocate a quantitative role for GC-MS in FAME analysis-an approach that would be particularly advantageous for FAME determination in complex biological samples, where spectrometric confirmation of analytes is advisable. To assess the utility of GC-MS methods for FAME quantification, a comparative study of GC-FID and GC-MS methods has been conducted. FAME in prepared solutions as well as a biological standard reference material were analyzed by GC-FID and GC-MS methods using both ion trap and quadrupole MS systems. Quantification by MS, based on total ion counts and processing of selected ions, was investigated for FAME ionized by electron impact. Instrument precision, detection limits, calibration behavior, and response factors were investigated for each approach, and quantitative results obtained by each technique were compared. Although there were a number of characteristic differences between the MS methods and FID with respect to FAME analysis, the quantitative performance of GC-MS compared satisfactorily with that of GC-FID. The capacity to combine spectrometric examination and quantitative determination advances GC-MS as a powerful alternative to GC-FID for FAME analysis.


Generalized information potential criterion for adaptive system training.
We have previously proposed the quadratic Renyi's error entropy as an alternative cost function for supervised adaptive system training. An entropy criterion instructs the minimization of the average information content of the error signal rather than merely trying to minimize its energy. In this paper, we propose a generalization of the error entropy criterion that enables the use of any order of Renyi's entropy and any suitable kernel function in density estimation. It is shown that the proposed entropy estimator preserves the global minimum of actual entropy. The equivalence between global optimization by convolution smoothing and the convolution by the kernel in Parzen windowing is also discussed. Simulation results are presented for time-series prediction and classification where experimental demonstration of all the theoretical concepts is presented.


Clinical Utility and Outcome Prediction of Early ZnT8-IgG Testing and Titer in Type 1 Diabetes
Type 1 diabetes autoantibodies are directed against multiple antigens including: glutamic acid decarboxylase, protein tyrosine phosphatase-like islet antigen 2 (IA2), insulin (IAA), and Zinc transporter 8 protein (ZnT8). The aim of our study was to determine if the presence or titer of ZnT8 antibodies (Ab) was predictive for clinical presentation at diagnosis or for the subsequent disease course. Between January, 2003 and May, 2019, 105 patients aged ≤21 years with a clinical diagnosis of type 1 diabetes mellitus had at least 1 autoantibody measured. A retrospective chart review was completed. At diagnosis, we evaluated the body mass index z-score, hemoglobin (HbA1c), and the presence of diabetic ketoacidosis (DKA). Complications analyzed post-diagnosis included episodes of DKA, the diagnosis of autoimmune disease, and the presence of vascular complications. We evaluated cumulative lifetime excess glucose as HbA1c area under the curve (AUC) >6%. Seventy-one patients were ZnT8-Ab(+) (68%), with 19 having low titer ZnT8-Ab and 52 with high titer ZnT8-Ab. Follow-up ranged from 10 days to 15.7 years (median 2.08 years). There were no differences in the characteristics at disease onset or in the subsequent follow-up between those with and those without ZnT8-Ab or those with high or low titers of ZnT8 Ab, except for a small but statistically significant difference in cumulative excess glucose (HbA1c AUC >6%) between those with low and high titers (p=0.0095). Our study adds to the limited literature on the effect of the presence and titer of ZnT8-Ab in pediatric diabetes. The small effect of ZnT8-Ab titer on glucose excess as measured by HbA1c AUC warrants further study.


Tests of a cellular model for constant branch distribution in the filamentous fungus Neurospora crassa.
The growth of mycelial fungi is characterized by the highly polarized extension of hyphal tips and the formation of subapical branches, which themselves extend as new tips. In Neurospora crassa, tip growth and branching are crucial elements for this saprophyte in the colonization and utilization of organic substrates. Much research has focused on the mechanism of tip extension, but a cellular model that fully explains the known phenomenology of branching by N. crassa has not been proposed. We described and tested a model in which the formation of a lateral branch in N. crassa was determined by the accumulation of tip-growth vesicles caused by the excess of the rate of supply over the rate of deposition at the apex. If both rates are proportional to metabolic rate, then the model explains the known lack of dependence of branch interval on growth rate. We tested the model by manipulating the tip extension rate, first by shifting temperature in both the wild type and hyperbranching (colonial) mutants and also by observing the behavior of both tipless colonies and colonyless tips. We found that temperature shifts in either direction result in temporary changes in branching. We found that colonyless tips also pass through a temporary transition phase of branching. The tipless colonies produced a cluster of new tips near the point of damage. We also found that branching in colonial mutants is dependent on growth rate. The results of these tests are consistent with a model of branching in which branch initiation is controlled by the dynamics of tip growth while being independent of the actual rate of this growth.


Design and methodological characteristics of studies using observational routinely collected health data for investigating the link between cancer and neurodegenerative diseases: protocol for a meta-research study.
Health services generate large amounts of routine health data (eg, administrative databases, disease registries and electronic health records), which have important secondary uses for research. Increases in the availability and the ability to access and analyse large amounts of data represent a major opportunity for conducting studies on the possible relationships between complex diseases. The objective of this study will be to evaluate the design, methods and reporting of studies conducted using observational routinely collected health data for investigating the link between cancer and neurodegenerative diseases. This is the protocol for a meta-research study. We registered the study protocol within the Open Science Framework: https://osf.io/h2qjg. We will evaluate observational studies (eg, cohort and case-control) conducted using routinely collected health data for investigating the associations between cancer and neurodegenerative diseases (such as Alzheimer's disease, amyotrophic lateral sclerosis/motor neuron disease, Huntington's disease, multiple sclerosis and Parkinson's disease). The following electronic databases will be searched (from their inception onwards): MEDLINE, Embase and Web of Science Core Collection. Screening and selection of articles will be conducted by at least two researchers. Potential discrepancies will be resolved via discussion. Design, methods and reporting characteristics in each article will be extracted using a standardised data extraction form. Information on general, methodological and transparency items will be reported. We will summarise our findings with tables and graphs (eg, bar charts, forest plots). Due to the nature of the proposed study, no ethical approval will be required. We plan to publish the full study in an open access peer-reviewed journal and disseminate the findings at scientific conferences and via social media. All data will be deposited in a cross-disciplinary public repository.


[The mechanisms of the effect of a high extracellular sodium concentration on the contractile activity of the isolated rat heart].
Increase in the extracellular concentration of sodium (from 140 mM to 200 mM) causes an initial increase in the developing left-ventricular pressure which is replaced by increase of the amplitude of contractions by 40-50% in comparison with the initial condition. Lithium chloride (60 mM) did not cause similar changes. The initial diminution of myocardial contractility under the effect of a hypersodium medium was not sensitive to verapamil, ethmosin, lidocaine, caffeine or the Na-H exchange blocker hexamethylenamyloride (HMA). Verapamil (0.1 microM) or HMA (1 microM) did not influence the increase in the developing pressure induced by the hypersodium medium. The favorable inotropic effect of the hypersodium medium was manifested after arrest of the heart with verapamil (2 microM). Caffeine (2 microM), ethmosin (1 microM) or lidocaine (100 microM) weakened the favorable effect of the hypernatrium medium.


SUPPRESSOR OF MORE AXILLARY GROWTH2 1 controls seed germination and seedling development in Arabidopsis.
Abiotic chemical signals discovered in smoke that are known as karrikins (KARs) and the endogenous hormone strigolactone (SL) control plant growth through a shared MORE AXILLARY GROWTH2 (MAX2)-dependent pathway. A SL biosynthetic pathway and candidate KAR/SL receptors have been characterized, but signaling downstream of MAX2 is poorly defined. A screen for genetic suppressors of the enhanced seed dormancy phenotype of max2 in Arabidopsis (Arabidopsis thaliana) led to identification of a suppressor of max2 1 (smax1) mutant. smax1 restores the seed germination and seedling photomorphogenesis phenotypes of max2 but does not affect the lateral root formation, axillary shoot growth, or senescence phenotypes of max2. Expression of three transcriptional markers of KAR/SL signaling, D14-LIKE2, KAR-UP F-BOX1, and INDOLE-3-ACETIC ACID INDUCIBLE1, is rescued in smax1 max2 seedlings. SMAX1 is a member of an eight-gene family in Arabidopsis that has weak similarity to HEAT SHOCK PROTEIN 101, which encodes a caseinolytic peptidase B chaperonin required for thermotolerance. SMAX1 and the SMAX1-like (SMXL) homologs are differentially expressed in Arabidopsis tissues. SMAX1 transcripts are most abundant in dry seed, consistent with its function in seed germination control. Several SMXL genes are up-regulated in seedlings treated with the synthetic SL GR24. SMAX1 and SMXL2 transcripts are reduced in max2 seedlings, which could indicate negative feedback regulation by KAR/SL signaling. smax1 seed and seedling growth mimics the wild type treated with KAR/SL, but smax1 seedlings are still responsive to 2H-furo[2,3-c]pyran-2-one (KAR2) or GR24. We conclude that SMAX1 is an important component of KAR/SL signaling during seed germination and seedling growth but is not necessary for all MAX2-dependent responses. We hypothesize that one or more SMXL proteins may also act downstream of MAX2 to control the diverse developmental responses to KARs and SLs.


Cryopreservation of Xenopus transgenic lines.
Xenopus laevis has been widely used for molecular, cellular, and developmental studies. With the development of the sperm-mediated transgenic method, it is now possible to study gene function during vertebrate development by using this popular model. On the other hand, like other animal species, it is labor intensive, and the maintenance of transgenic lines is expensive. In this article, we investigated the possibility of using sperm-cryopreservation as a means to preserve transgenic frog lines. We demonstrated that cryopreserved sperms are viable but not fertile under our in vitro fertilization (IVF) conditions. However, by microinjecting cryopreserved sperm nuclei, we successfully regenerated a transgenic line carrying a double promoter transgene construct, where the marker gene encoding the green fluorescent protein (GFP) is driven by the gamma-crystallin gene promoter and a gene of interest, encoding a fusion protein of GFP with the matrix metalloproteinase stromelysin-3 (ST3-GFP), is driven by a heat shock-inducible promoter. We demonstrated the functional transmission of the ST3-GFP transgene by analyzing the phenotype of the F1 animals after heat-shock to induce its expression. Our method thus provides an inexpensive means to preserve transgenic frog lines and a convenient way for distribution of transgenic lines. Furthermore, the ease with which to microinject nuclei compared to the technically demanding transgenesis procedure with variable outcome should facilitate more laboratories to use transgenic Xenopus laevis for functional studies in vivo. Mol. Reprod. Dev. 67: 65-69, 2004.


Concurrent validity of the tower tasks as measures of executive function in adults: a meta-analysis.
Executive function refers to a variety of behaviors and abilities related to planning and strategy use, as well as to the maintenance of attention and behavior in the pursuit of some goal. Many instruments have been designed for the purpose of assessing executive function, and the tower tasks represent a specific group of measures commonly used in the assessment of this construct. This review and meta-analysis examines the theoretical and psychometric basis for the use of the various tower tasks in neuropsychological assessment of adults. Neuroimaging and electrophysiological evidence are consistent with theoretical hypotheses of frontal involvement (e.g., planning and strategy use) in tower task performance. Further, adults with various disorders of presumed neurological basis demonstrate impaired performance on tower tasks. Implications for the use of tower tasks in practice and research are discussed.


[An elderly couple and their long life raising four schizophrenic children].
The objective was to identify, among parents of schizophrenics, elements of their daily life in coping with the disorder and the care offered and received through the health system. This is a field research, using thematic oral history. The parents of four patients with schizophrenia took part in this study. Interviews were conducted, recorded and transcribed, based on three instruments (two specific questionnaires and a field diary). Three categories were identified that reflect difficulties experienced in daily life: limitations in knowledge about schizophrenia; fatigue and burden with impairment of quality of life; and uncertainly about the future and resilience strengthened by faith in God. The concept of care was associated with technical procedures, revealing general satisfaction with the care received. The suffering related to living with schizophrenic relatives is intense, and professionals must be prepared to deal with these experiences of pain and suffering from patients with mental disorder and their relatives.


Persistent HIF-1alpha activation in gut ischemia/reperfusion injury: potential role of bacteria and lipopolysaccharide.
In both animal models of hemorrhagic shock and clinical settings, shock-induced gut ischemia has been implicated in the development of the systemic inflammatory response syndrome and distant organ injury, yet the factors transducing these events remain to be fully determined. Because hypoxia-inducible factor (HIF-1), a transcription factor composed of oxygen-labile HIF-1alpha and constitutive HIF-1beta subunits, regulates the physiologic/pathophysiologic response to hypoxia and ischemia, we examined the HIF-1 response in two rat models of gut ischemia-reperfusion. We found that ileal nuclear HIF-1alpha protein levels were induced in rats subjected to trauma (laparotomy) plus hemorrhagic shock for 90 min relative to their trauma sham-shock and naïve counterparts and that this trauma hemorrhagic shock-induced mucosal HIF-1alpha protein response persisted after 1 h and 3 h of reperfusion. Likewise, in a model of isolated gut ischemia-reperfusion injury, where the superior mesenteric artery was occluded for 45 min, nuclear HIF-1alpha were induced in the gut mucosa relative to their sham counterparts and persisted after 1 h and 3 h or reperfusion. Similar to the in vivo response, in vitro hypoxia induced HIF-alpha expression in three different enterocyte cell lines (rat IEC-6 and human Caco-2 and HT-29 cell lines). However, in contrast to the in vivo response, HIF-1 expression rapidly disappeared on subsequent reoxygenation. Because in vivo enterocytes are exposed to bacteria, we tested whether the in vitro HIF-1alpha response would persist on reoxygenation if the enterocytes were cocultured with bacteria. P. aeruginosa, an enteric bacterium, markedly induced enterocyte HIF-1alpha protein levels under normoxic conditions. Furthermore, the addition of P. aeruginosa during either the hypoxic or reoxygenation phase prevented the degradation of HIF-1alpha protein levels. Moreover, the observation that lipopolysaccharide induced HIF-1alpha expression in a time-dependent manner in IEC-6 cells indicated that the induction of HIF-1 by exposure to P. aeruginosa is not dependent on bacterial viability. In conclusion, these results suggest that HIF-1alpha activation is an early reperfusion-independent event in models of gut ischemia-reperfusion and that this HIF-1alpha response is potentiated by the presence of P. aeruginosa or lipopolysaccharide.


Schizocladia ischiensis: a new filamentous marine chromophyte belonging to a new class, Schizocladiophyceae.
A new marine filamentous chromophyte Schizocladia ischiensis sp. nov. is described from Naples, Italy, and a new class, Schizocladiophyceae, is proposed to accommodate the species based on morphology, photosynthetic pigment analysis, and rbcL and 18S rRNA gene sequences. The vegetative thallus is composed of branched filaments, 3-7 microm in diameter, containing one to two light brown parietal plastids. Cell walls are composed of layered fibers containing alginates, but lacking cellulose. Plastids are of the typical chromophyte type, containing chlorophylls a and c, and abundant fucoxanthin. Zoospores are formed by direct transformation of vegetative cells or through a process including a multinucleated cell stage. Zoospores are teardrop-shaped with a longer anterior flagellum with tubular mastigonemes and a shorter smooth posterior flagellum with a basal swelling. Flagella have a single basal plate and multi-gyred transitional helix distal to the basal plate. Each zoospore has an eyespot. Phylogenetic analyses using rbcL and 18S rDNA sequences suggest the closest phylogenetic relationship with Phaeophyceae, and then with Xanthophyceae and Phaeothamniophyceae. Nevertheless, Schizocladia differs from Phaeophyceae in some essential features (i.e. cell wall lacking cellulose and plasmodesmata, presence of flagellar transitional helix). Therefore, an independent class Schizocladiophyceae is proposed to accommodate this new taxon.


Myeloid-derived suppressor cells and myeloid regulatory cells in cancer and autoimmune disorders.
Myeloid-derived suppressor cells (MDSCs) were originally described as a heterogeneous population of immature cells derived from myeloid progenitors with immune-suppressive functions in tumor-bearing hosts. In recent years, increasing number of studies have described various populations of myeloid cells with MDSC-like properties in murine models of cancer and autoimmune diseases. These studies have observed that the populations of MDSCs are increased during inflammation and autoimmune conditions. In addition, MDSCs can effectively suppress T cell responses and modulate the activity of natural killer cells and other myeloid cells. MDSCs have also been implicated in the induction of regulatory T cell production. Furthermore, these cells have the potential to suppress the autoimmune response, thereby limiting tissue injury. Myeloid regulatory cells (Mregs) are recently attracting increasing attention, since they function in proinflammatory and immune suppression in autoimmune diseases, as well as in various types of cancer. Currently, research focus is directed from MDSCs to Mregs in cancer and autoimmune diseases. The present study reviewed the suppressive roles of MDSCs in various autoimmune murine models, the immune modulation of MDSCs to T helper 17 lymphocytes, as well as the proinflammatory and immunosuppressive roles of Mregs in various types of cancer and autoimmune diseases.


The spectrum of MEFV gene mutations and genotypes in Van province, the eastern region of Turkey, and report of a novel mutation (R361T).
Familial Mediterranean fever (FMF) is the most common hereditary inflammatory periodic disease, characterized by recurrent episodes of fever and abdominal pain, synovitis, and pleuritis. The aim of this study was to determine the frequency and distribution of Mediterranean fever (MEFV) gene mutations in Van province of Eastern Anatolia and to compare them with the other studies from various regions of Turkey. Therefore, we retrospectively evaluated MEFV gene mutations in 1058 pediatric patients with suspected FMF. The MEFV gene mutations were investigated using Sanger sequencing and the multiplex minisequencing technique. We identified 37 different genotypes and 16 different mutations. The four most common mutations and allelic frequencies were M694V (36.50%), E148Q (32.77%), V726A (14.09%), and M694I (4.41%). M694V was the most common mutation, and the M694I frequency was found to be higher compared to studies from other regions of Turkey. In addition, we identified a novel missense mutation (R361T, c.1082G>C) in exon 3 of the MEFV gene in a 12-year-old boy, who had a typical FMF phenotype. In conclusion, this study evaluated the distribution of MEFV gene mutations in children with FMF as the first study conducted in Van province, Eastern Anatolia.


A commentary on decision-making and organisational legitimacy in the Risk Society.
Key concepts of Risk Society as elaborated by Ulrich Beck and others (Beck, U., 1992 (trans. Mark Ritter). The Risk Society. Sage Publications, London. Beck, U., 1995, Ecological Politics in the Age of Risk. Polity Press, Cambridge. Beck, U., 1999, World Risk Society. Polity Press, Cambridge. Giddens, A., 1994, Beyond Left and Right. Polity Press, Oxford. Beck, U., Giddens, A. and Lash, S., 1994, Reflexive Modernisation: Politics, Tradition and Aesthetics in the Modern Social Order. Stanford University Press, Stanford. Beck, U., Bonss, W. and Lau, C., 2003, Theory, Culture & Society 2003, Sage, London, 20(2), pp. 1-33.) are illuminated though a case study of managed environmental risk, namely the hexachlorobenzene (HCB) controversy at Botany, a southeast suburb of Sydney. We observe the way multiple stakeholder decision-making plays out a number of Risk Society themes, including the emergence of 'unbounded risk' and of highly 'individualised' and 'reflexive' risk communities. Across several decades, the events of the HCB story support Risk Society predictions of legitimacy problems faced by corporations as they harness technoscientific support for innovation in their products and industrial processes without due recognition of social and environmental risk. Tensions involving identity, trust and access to expert knowledge advance our understanding of democratic 'sub-political' decision-making and ways of distributing environmental risk.


Rice bacterial blight pathogen Xanthomonas oryzae pv. oryzae produces multiple DSF-family signals in regulation of virulence factor production.
Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of rice bacterial blight disease. Xoo produces a range of virulence factors, including EPS, extracellular enzyme, iron-chelating siderophores, and type III-secretion dependent effectors, which are collectively essential for virulence. Genetic and genomics evidence suggest that Xoo might use the diffusible signal factor (DSF) type quorum sensing (QS) system to regulate the virulence factor production. However, little is known about the chemical structure of the DSF-like signal(s) produced by Xoo and the factors influencing the signal production. Xoo genome harbours an rpf cluster comprising rpfB, rpfF, rpfC and rpfG. The proteins encoded by these genes are highly homologous to their counterparts in X. campestris pv. campestris (Xcc), suggesting that Xcc and Xoo might use similar mechanisms for DSF biosynthesis and autoregulation. Consistent with in silico analysis, the rpfF mutant was DSF-deficient and the rpfC mutant produced about 25 times higher DSF-like activity than the wild type Xoo strain KACC10331. From the supernatants of rpfC mutant, we purified three compounds showing strong DSF-like activity. Mass spectrometry and NMR analysis revealed that two of them were the previously characterized DSF and BDSF; the third one was a novel unsaturated fatty acid with 2 double bonds and was designated as CDSF in this study. Further analysis showed that all the three DSF-family signals were synthesized via the enzyme RpfF encoded by Xoo2868. DSF and BDSF at a final concentration of 3 microM to the rpfF mutant could fully restore its extracellular xylanase activity and EPS production to the wild type level, but CDSF was less active than DSF and BDSF in induction of EPS and xylanase. DSF and CDSF shared a similar cell density-dependent production time course with the maximum production being detected at 42 h after inoculation, whereas the maximum production of BDSF was observed at 36 h after inoculation. When grown in a rich medium such as YEB, LB, PSA, and NYG, Xoo produced all the three signals with the majority being DSF. Whereas in nutritionally poor XOLN medium Xoo only produced BDSF and DSF but the majority was BDSF. This study demonstrates that Xoo and Xcc share the conserved mechanisms for DSF biosynthesis and autoregulation. Xoo produces DSF, BDSF and CDSF signals in rich media and CDSF is a novel signal in DSF-family with two double bonds. All the three DSF-family signals promote EPS production and xylanase activity in Xoo, but CDSF is less active than its analogues DSF and BDSF. The composition and ratio of the three DSF-family signals produced by Xoo are influenced by the composition of culture media.


Assessing Cannabidiol as a Therapeutic Agent for Preventing and Alleviating Alzheimer's Disease Neurodegeneration.
Alzheimer's disease (AD) is a leading neurodegenerative condition causing cognitive and memory decline. With small-molecule drugs targeting Aβ proving ineffective, alternative targets are urgently needed. Neuroinflammation, which is central to AD's pathology, results in synaptic and neuronal damage, highlighting the importance of addressing inflammation and conserving neuronal integrity. Cannabidiol (CBD), derived from cannabis, is noted for its neuroprotective and anti-inflammatory properties, having shown efficacy in neuropathic pain management for epilepsy. To investigate the therapeutic efficacy of CBD in AD and to elucidate its underlying mechanisms, we aimed to contribute valuable insights for incorporating AD prevention recommendations into future CBD nutritional guidelines. Aβ1-42 was employed for in vivo or in vitro model establishment, CBD treatment was utilized to assess the therapeutic efficacy of CBD, and RNA-seq analysis was conducted to elucidate the underlying therapeutic mechanism. CBD mitigates Aβ-induced cognitive deficits by modulating microglial activity, promoting neurotrophic factor release, and regulating inflammatory genes. The administration of CBD demonstrated a protective effect against Aβ toxicity both in vitro and in vivo, along with an amelioration of cognitive impairment in mice. These findings support the potential inclusion of CBD in future nutritional guidelines for Alzheimer's disease prevention.


Allergic responses to the biopesticide Metarhizium anisopliae in Balb/c mice.
Metarhizium anisopliae is used as a microbial pesticide to control cockroaches and other insects. M. anisopliae has demonstrated neither infectivity nor toxicity in mammals. However, allergenicity has not been assessed. M. anisopliae is a prototype for other organisms released into the environment for pesticide or other beneficial applications. Hence this study is part of an effort to develop methods for screening such organisms for allergenic potential. Soluble factors from fungal components were combined in equal protein amounts to form a crude fungal antigen (MACA). Balb/c mice were intratracheally (IT) challenged with 25 micrograms fungal antigen 13 days post intraperitoneal sensitization with the fungal antigen in alhydrogel adjuvant. Additionally, mice were sensitized with adjuvant alone or chitin media in adjuvant as experimental controls. Serum and bronchoalveolar lavage fluid (BALF) were harvested prior to challenge and at 1 and 7 days post IT challenge (DPIT). These mice exhibited immune and pulmonary inflammatory responses to MACA characteristic of allergy. Total serum IgE for antigen-sensitized animals increased 7.6- and 14.7-fold over that for chitin media and adjuvant controls, respectively, at 7 DPIT. Less striking increases were seen at 24 DPIT and prior to challenge. BALF IL-4 was dramatically elevated only in MACA-sensitized and challenged mice and only at 1 DPIT. Additionally, there was a dose-dependent increase in BALF eosinophils from MACA-sensitized mice at both 1 and 7 DPIT. While lymphocyte counts were increased for all treatment groups at 1 DPIT, by 7 DPIT lymphocyte counts for MACA-sensitized mice only were significantly elevated compared to controls. Pulmonary inflammation, edema, and cell damage were apparent at 1 DPIT (25 micrograms MACA), as indicated by a neutrophilic influx and elevated levels of total protein and LDH, in both sensitized and control groups. These effects were significantly decreased, but not eliminated by reduction of the challenge dose to either 10 or 5 micrograms MACA. While BALF IL-4 was also reduced at the lower challenge doses, eosinophilia and total IgE were unchanged. The data suggest that the crude fungal extract MACA contains one or more potent allergens and that total IgE may be useful in the identification of the allergen(s).


Dent-Wrong disease and other rare causes of the Fanconi syndrome.
Dent-Wrong disease, an X-linked recessive disorder of the proximal tubules, presents with hypercalciuria, nephrocalcinosis, nephrolithiasis, renal insufficiency, low-molecular-weight proteinuria, rickets and/or osteomalacia. Dent and Friedman initially characterized the disorder in 1964 following studies of two patients with rickets who presented with hypercalciuria, hyperphosphaturia, proteinuria and aminoaciduria. Since then, extensive investigation identified two genetic mutations (CLCN5 and OCRL1) to be associated with Dent-Wrong disease. Clinical features supported by laboratory findings consistent with proximal tubule dysfunction help diagnose Dent-Wrong disease. Genetic analysis supports the diagnosis; however, these two genes can be normal in a small subset of patients. The differential diagnosis includes other forms of the Fanconi syndrome, which can be hereditary or acquired (e.g. those related to exposure to exogenous substances). Treatment is supportive with special attention to the prevention of nephrolithiasis and treatment of hypercalciuria. We review the rare forms of Fanconi syndrome with special attention to Dent-Wrong disease.


School wellness team best practices to promote wellness policy implementation.
Schools with wellness teams are more likely to implement federally mandated Local Wellness Policies (LWPs, Local Education Agency-level policies for healthy eating/physical activity). Best practices have been developed for wellness teams based on minimal empirical evidence. The purpose of this study is to determine, among schools with wellness teams, associations between LWP implementation and six wellness team best practices (individually and as a sum score). An online survey targeting Maryland school wellness leaders/administrators (52.4% response rate, 2012-2013 school year) was administered that included LWP implementation (17-item scale: categorized as no, low, and high implementation) and six wellness team best practices. Analyses included multi-level multinomial logistic regression. Wellness teams were present in 311/707 (44.0%) schools, with no (19.6%), low (36.0%), and high (44.4%) LWP implementation. A sum score representing active wellness teams (mean=2.6) included: setting healthy eating/physical activity goals (66.9%), informing the public of LWP activities (71.4%), meeting ≥4times/year (45.8%), and having school staff (46.9%), parent (25.4%), or student (14.8%) representation. In adjusted models, goal setting, meeting ≥4times/year, and student representation were associated with high LWP implementation. For every one-unit increase in active wellness team sum score, schools were 41% more likely to be in high versus no implementation (Likelihood Ratio=1.41, 95% C.I.=1.13, 1.76). In conclusion, wellness teams meeting best practices are more likely to implement LWPs. Interventions should focus on the formation of wellness teams with recommended composition/activities. Study findings provide support for wellness team recommendations stemming from the 2016 Healthy, Hunger-Free Kids Act final rule.


Time-lapse in vivo imaging of the morphological development of Xenopus optic tectal interneurons.
Excitatory and inhibitory interneurons play a key role in the establishment of neuronal responses and circuit properties in the brain. Despite their importance in brain function, the structural development of interneurons has not been well studied. We used in vivo time-lapse imaging in intact anesthetized Xenopus tadpoles to determine the morphological events underlying the development of interneuron dendritic arbor structure. Single optic tectal neurons were labeled with DiI and imaged at daily intervals over 4 days in intact albino Xenopus tadpoles. The same neurons were also imaged at shorter intervals to determine the dynamic rearrangements in arbor branches that accompany large-scale arbor growth. Tectal interneurons, like projection neurons, develop from neuroepithelial cells located near the ventricular layer. They elaborate complex dendritic arbors over a period of 2 days. Short-interval time-lapse images reveal that tectal interneuron arbors have rapid rates of branch additions and retractions. We identified four patterns of interneuron arbor development, based on the cell morphology and types of structural rearrangements that occur over the development of the neuronal arbor. A surprising feature of interneuronal development is the large extent of structural rearrangements: many interneurons extend transient processes so that the neuronal structure is dramatically different from one day to the next. Because the majority of synaptic contacts are formed on dendrites, the structural changes we observed in interneuronal dendritic arbors suggest that optic tectal circuits are extremely plastic during early stages of development.


Ethics Across the Curriculum: Prospects for Broader (and Deeper) Teaching and Learning in Research and Engineering Ethics.
The movements to teach the responsible conduct of research (RCR) and engineering ethics at technological universities are often unacknowledged aspects of the ethics across the curriculum (EAC) movement and could benefit from explicit alliances with it. Remarkably, however, not nearly as much scholarly attention has been devoted to EAC as to RCR or to engineering ethics, and RCR and engineering ethics educational efforts are not always presented as facets of EAC. The emergence of EAC efforts at two different institutions-the Illinois Institute of Technology and Utah Valley University (UVU)-provide counter examples. The remarkably successful UVU initiative gave birth to EAC as a scholarly movement and to the associated Society for Ethics Across the Curriculum. EAC initiatives at the Colorado School of Mines, however, point up continuing institutional resistances to EAC. Finally, comparative reflection on successes and failures can draw some lessons for the future. One suggestion is that increasing demands for accountability and pedagogical research into what works in teaching and learning offers special opportunities.


Effects of nonionic surfactant on enzymatic hydrolysis of used newspaper.
Effects of five types of nonionic surfactant having a polyoxyethylene glycol (POG) group on enzymatic hydrolysis of used newspaper were studied. The surfactants examined in this work always enhanced the saccharification. The optimum surfactant concentration was 0.05% (wt/substrate wt) in the case of POG(21) sorbitane oleic ester. Among the surfactants, POG phenyl ether types showed the highest enhancement effect, for example, with two times higher conversion at 80 h than that without surfactant. Using POG nonylphenyl ether series, the effects of surfactant were considered from the point of the HLB (hydrophile-lypophile balance) value. The GFC (gel filtration chromatography) analysis of free enzyme quantity were also done to study the effect of surfactant on enzyme adsorption onto substrate. As the HLB value increased, the free enzyme quantity and the conversion both increased. It appears that surfactants help the enzyme to desorb from the binding site on the substrate surface after the completion of saccharification at that site.


Gender-specific effects of fluoxetine on hippocampal glucocorticoid receptor phosphorylation and behavior in chronically stressed rats.
Chronic psychosocial isolation stress (CPSI) modulates glucocorticoid receptor (GR) functioning in Wistar male rat hippocampus (HIPPO) through alteration of nuclear GR phosphorylation and its upstream kinases signaling, which parallels animal depressive-like behavior. The current study investigated potential gender specificities regarding the effect of chronic therapy by an antidepressant fluoxetine (FLU) on GR signaling in HIPPO and depressive-like behavior in CPSI animals. FLU was administrated to female and male naïve or CPSI rats for 21 days and GR protein, its phosphorylation status and upstream kinases, as well as GR and BDNF mRNA were followed in HIPPO together with animal serum corticosterone (CORT) and depressive-like behavior. The results showed that CPSI increased immobility in males versus hyperactivity in females and disrupted nuclear pGR232-Cdk5 pathway and JNK signaling in a gender-specific way. In contrast, in both genders CPSI increased the nuclear levels of GR and pGR246 but decreased CORT and mRNA levels of GR and BDNF. Concomitant FLU normalized the depressive-like behavior and altered the nuclear pGR232-Cdk5 signaling in a gender-specific manner. In both females and males, FLU reversed the nuclear levels of GR and pGR246 without affecting CORT and GR mRNA levels. In contrast, FLU exhibited gender-specific effect on BDNF mRNA in CPSI animals, by increasing it in females, but not in males. In spite of normalization the total nuclear GR level upon FLU treatment in both gender, down-regulation of GR mRNA is possibly maintained through prevalence of pGR232 isoform only in males. The gender-specific alterations of pGR232-Cdk5 signaling and BDNF gene expression in HIPPO and normalization of depressive-like behavior upon FLU treatment distinguishes this signaling pathway as potential future antidepressant target for gender-specific therapy of stress related mood disorders.


Primary care management of chronic musculoskeletal pain.
Chronic musculoskeletal pain, a common problem seen in the primary care setting, is often frustrating for both the patient and the clinician. Despite its prevalence, chronic pain is often poorly understood and inconsistently managed by health care providers. Unlike acute pain, chronic pain serves no biologic function and persists long after the tissue has healed from injury. Patients with chronic pain may become isolated from friends and family, lose their jobs, and develop depression. Nonpharmacologic techniques such as acupuncture, massage, and relaxation may be helpful to the patient with chronic pain. In addition to nonsteroidal antiinflammatory drugs, antidepressants and opioid analgesics are useful for treating chronic musculoskeletal pain. This article explains that pathophysiology of chronic pain, lists aspects of chronic pain that distinguish it from acute pain, and develops a general primary care plan for patients with chronic musculoskeletal pain.


Transcriptional regulators in the Hippo signaling pathway control organ growth in Xenopus tadpole tail regeneration.
The size and shape of tissues are tightly controlled by synchronized processes among cells and tissues to produce an integrated organ. The Hippo signaling pathway controls both cell proliferation and apoptosis by dual signal-transduction states regulated through a repressive kinase cascade. Yap1 and Tead, transcriptional regulators that act downstream of the Hippo signaling kinase cascade, have essential roles in regulating cell proliferation. In amphibian limb or tail regeneration, the local tissue outgrowth terminates when the correct size is reached, suggesting that organ size is strictly controlled during epimorphic organ-level regeneration. We recently demonstrated that Yap1 is required for the regeneration of Xenopus tadpole limb buds (Hayashi et al., 2014, Dev. Biol. 388, 57-67), but the molecular link between the Hippo pathway and organ size control in vertebrate epimorphic regeneration is not fully understood. To examine the requirement of Hippo pathway transcriptional regulators in epimorphic regeneration, including organ size control, we inhibited these regulators during Xenopus tadpole tail regeneration by overexpressing a dominant-negative form of Yap (dnYap) or Tead4 (dnTead4) under a heat-shock promoter in transgenic animal lines. Each inhibition resulted in regeneration defects accompanied by reduced cell mitosis and increased apoptosis. Single-cell gene manipulation experiments indicated that Tead4 cell-autonomously regulates the survival of neural progenitor cells in the regenerating tail. In amphibians, amputation at the proximal level of the tail (deep amputation) results in faster regeneration than that at the distal level (shallow amputation), to restore the original-sized tail with similar timing. However, dnTead4 overexpression abolished the position-dependent differential growth rate of tail regeneration. These results suggest that the transcriptional regulators in the Hippo pathway, Tead4 and Yap1, are required for general vertebrate epimorphic regeneration as well as for organ size control in appendage regeneration. In regenerative medicine, these findings should contribute to the development of three-dimensional organs with the correct size for a patient's body.


Differential effects of clozapine versus other antipsychotics on clinical outcome and dopamine release in the brain.
The first atypical antipsychotic, clozapine (Clozaril), dramatically improved the outcome of treatment of patients with schizophrenia in two ways. First, it reduced psychotic symptoms without eliciting significant neurological side effects. Second, it was effective in approximately 30% of individuals who were previously refractory to treatment. Efforts to develop similar drugs have been partially successful in that newer antipsychotics are also less likely to produce neurological side effects. However, it has not yet been established that the newest antipsychotics are more effective than conventional agents in individuals who are refractory to treatment. In the first part of this review, the results of studies that evaluated the new antipsychotics and provided an outcome measure of response rate (regardless of how this index was defined) are summarized. Even with this broad criterion, the evidence suggests that the newer antipsychotics do not share the clinical advantages of clozapine. To explore the possible mechanisms for the clinical advantage of clozapine, evidence of antipsychotic-induced dopamine release in the brain is discussed in the second half of this article. This analysis indicates that acute clozapine administration induces the release of more dopamine in the cortex than in the striatum or limbic system. With conventional antipsychotics, this relationship is reversed. The newest antipsychotics do not show a preference among these sites. Moreover, after long-term treatment, tolerance develops to haloperidol, but not to clozapine, with regard to the amount of dopamine released in the brain. No data are available on the newest antipsychotics. Although more studies need to be done-especially studies of the effects of long-term administration of various conventional and atypical antipsychotics-this distinction might be relevant to the unique clinical advantage of clozapine.


Phase transition kinetics and surface binding states of methylammonium lead iodide perovskite.
We have presented a detailed analysis of the phase transition kinetics and binding energy states of solution processed methylammonium lead iodide (MAPbI3) thin films prepared at ambient conditions and annealed at different elevated temperatures. It is the processing temperature and environmental conditions that predominantly control the crystal structure and surface morphology of MAPbI3 thin films. The structural transformation from tetragonal to cubic occurs at 60 °C with a 30 minute annealing time while the 10 minute annealed films posses a tetragonal crystal structure. The transformed phase is greatly intact even at the higher annealing temperature of 150 °C and after a time of 2 hours. The charge transfer interaction between the Pb 4f and I 3d oxidation states is quantified using XPS.


EPAS1 Is Required for Spermatogenesis in the Postnatal Mouse Testis.
Spermatogenesis, a process involving the differentiation of spermatogonial stem cells into mature spermatozoa, takes place throughout masculine life. A complex system in the testis, including endocrine signaling, physical interactions between germ and somatic cells, spermatocyte meiosis, and timely release of spermatozoa, controls this cycle. We demonstrate herein that decreased O(2) levels and Epas1 activation are critical components of spermatogenesis. Postnatal Epas1 ablation leads to male infertility, with reduced testis size and weight. While immature spermatogonia and spermatocytes are present in Epas1(Delta/Delta) testes, spermatid and spermatozoan numbers are dramatically reduced. This is not due to germ cell-intrinsic defects. Rather, Epas(Delta/Delta) Sertoli cells exhibit decreased ability to form tight junctions, thereby disrupting the blood-testis barrier necessary for proper spermatogenesis. Reduced numbers of tight junction complexes are due to decreased expression of multiple genes encoding tight junction proteins, including TJP1 (ZO1), TJP2 (ZO2), and occludin. Furthermore, Epas1(Delta/Delta) testes exhibit disrupted basement membranes surrounding the seminiferous tubules, causing the premature release of incompletely differentiated germ cells. We conclude that low O(2) levels in the male gonad regulate germ cell homeostasis in this organ via EPAS1.


Amblyomma americanum serpin 27 (AAS27) is a tick salivary anti-inflammatory protein secreted into the host during feeding.
Ticks successfully feed and transmit pathogens by injecting pharmacological compounds in saliva to thwart host defenses. We have previously used LC-MS/MS to identify proteins that are present in saliva of unfed Amblyomma americanum ticks that were exposed to different hosts. Here we show that A. americanum serine protease inhibitor (serpin) 27 (AAS27) is an immunogenic saliva protein that is injected into the host within the first day of tick feeding and is an anti-inflammatory protein that might act by blocking plasmin and trypsin functions. Although AAS27 is injected into the host throughout tick feeding, qRT-PCR and western blotting analyses indicate that the respective transcript and protein are present in high amounts within the first 24 h of tick feeding. Biochemical screening of Pichia pastoris-expressed recombinant (r) AAS27 against mammalian proteases related to host defense shows it is an inhibitor of trypsin and plasmin, with stoichiometry of inhibition indices of 3.5 and 3.8, respectively. Consistent with typical inhibitory serpins, rAAS27 formed heat- and SDS-stable irreversible complexes with both proteases. We further demonstrate that rAAS27 inhibits trypsin with ka of 6.46 ± 1.24 x 104 M-1 s-1, comparable to serpins of other tick species. We show that native AAS27 is part of the repertoire of proteins responsible for the inhibitory activity against trypsin in crude tick saliva. AAS27 is likely utilized by the tick to evade the hosts inflammation defense since rAAS27 blocks both formalin and compound 48/80-induced inflammation in rats. Tick immune sera of rabbits that had acquired resistance against tick feeding following repeated infestations with A. americanum or Ixodes scapularis ticks reacts with rAAS27. Of significant interest, antibody to rAAS27 blocks this serpin inhibitory functions. Taken together, we conclude that AAS27 is an anti-inflammatory protein secreted into the host during feeding and may represent a potential candidate for development of an anti-tick vaccine.