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Sample records for key anabolic factors

  1. Risk factors for anabolic-androgenic steroid use in men.

    PubMed

    Brower, K J; Blow, F C; Hill, E M

    1994-01-01

    The illicit use of anabolic steroids to enhance athletic performance and physical appearance can cause numerous psychiatric and other adverse effects. In order to prevent steroid use and its negative consequences, knowledge of risk factors is needed. We conducted an anonymous survey of 404 male weight lifters from community gymnasiums who completed a 20-min, self-administered questionnaire. The sample for this study included all 35 men who were thinking about using steroids ("high-risk" nonusers), 50 randomly selected nonusers who were not thinking about using steroids ("low-risk" nonusers) and all 49 steroid users. The three groups differed in age, training characteristics, other performance-enhancers tried, body image, acquaintance with steroid users, and perception of negative consequences. When groups were compared along a continuum from low risk to high risk and from high risk to actual use, we found increasing amounts of competitive bodybuilding, performance-enhancers tried, and steroid-using acquaintances. Groups did not differ in their use of addictive substances. Nearly three-fourths of the high-risk group felt "not big enough," compared to 21% of the low-risk group and 38% of the steroid users (p < .001). These data suggest that steroids do work to increase satisfaction with body size, and that dissatisfaction with body size may contribute to the risk of using steroids.

  2. Anabolic Steroids

    MedlinePlus

    Anabolic steroids are man-made substances related to male sex hormones. Doctors use anabolic steroids to treat some hormone problems in men, delayed ... from some diseases. Bodybuilders and athletes often use anabolic steroids to build muscles and improve athletic performance. Using ...

  3. Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting.

    PubMed

    Gullett, Norleena P; Hebbar, Gautam; Ziegler, Thomas R

    2010-04-01

    This article and others that focused on the clinical features, mechanisms, and epidemiology of skeletal muscle loss and wasting in chronic diseases, which include chronic kidney disease, cancer, and AIDS, were presented at a symposium entitled "Cachexia and Wasting: Recent Breakthroughs in Understanding and Opportunities for Intervention," held at Experimental Biology 2009. The clinical and anabolic efficacy of specific growth factors and anabolic steroids (eg, growth hormone, testosterone, megestrol acetate) in malnutrition and other catabolic states has been the subject of considerable research during the past several decades. Research on the effects of these agents in cachexia or wasting conditions, characterized by progressive loss of skeletal muscle and adipose tissue, focused on patients with AIDS in the early 1990s, when the devastating effects of the loss of body weight, lean body mass, and adipose tissue were recognized as contributors to these patients' mortality. These same agents have also been studied as methods to attenuate the catabolic responses observed in cancer-induced cachexia and in wasting induced by chronic obstructive pulmonary disease, congestive heart failure, renal failure, and other conditions. This article provides an updated review of recent clinical trials that specifically examined the potential therapeutic roles of growth hormone, testosterone, oxandrolone, and megestrol acetate and emerging data on the orexigenic peptide ghrelin, in human cachexia and wasting.

  4. Interactions of anabolic steroids.

    PubMed

    Kopera, H

    1993-01-01

    Drug-drug interactions, or interference between drugs and other treatments, depend on many factors and are therefore difficult to predict. However, a number are clearly established in the case of anabolic-androgenic steroids. The beneficial interactions between anabolic steroids and radiotherapy or cytostatic drugs respectively are of therapeutic value. Adjuvant treatment with anabolic compounds in patients undergoing radiation and/or cytostatic therapy is beneficial because it can prevent or reduce depression of erythropoiesis, granulopoiesis and thrombopoiesis. It also diminishes protein catabolism, supports recovery, improves the general condition of the patient and minimizes radiation sickness. Potentially adverse interactions with anabolic steroids must be expected in the case of oral anticoagulants and antidiabetic drugs, since sensitivity to each of the latter is increased. This makes it particularly advisable to monitor patients receiving either oral anticoagulants or antidiabetic treatment concurrently with anabolic drugs.

  5. Anabolic steroids.

    PubMed

    Kuhn, Cynthia M

    2002-01-01

    The term "anabolic steroids" refers to testosterone derivatives that are used either clinically or by athletes for their anabolic properties. However, scientists have questioned the anabolic effects of testosterone and its derivatives in normal men for decades. Most scientists concluded that anabolic steroids do not increase muscle size or strength in people with normal gonadal function and have discounted positive results as unduly influenced by positive expectations of athletes, inferior experimental design, or poor data analysis. There has been a tremendous disconnect between the conviction of athletes that these drugs are effective and the conviction of scientists that they aren't. In part, this disconnect results from the completely different dose regimens used by scientists to document the correction of deficiency states and by athletes striving to optimize athletic performance. Recently, careful scientific study of suprapharmacologic doses in clinical settings - including aging, human immunodeficiency virus, and other disease states - supports the efficacy of these regimens. However, the mechanism by which these doses act remains unclear. "Anabolism" is defined as any state in which nitrogen is differentially retained in lean body mass, either through stimulation of protein synthesis and/or decreased breakdown of protein anywhere in the body. Testosterone, the main gonadal steroid in males, has marked anabolic effects in addition to its effects on reproduction that are easily observed in developing boys and when hypogonadal men receive testosterone as replacement therapy. However, its efficacy in normal men, as during its use in athletes or in clinical situations in which men are eugonadal, has been debated. A growing literature suggests that use of suprapharmacologic doses can, indeed, be anabolic in certain situations; however, the clear identification of these situations and the mechanism by which anabolic effects occur are unclear. Furthermore, the

  6. Risk factors for anabolic-androgenic steroid use among weightlifters: a case-control study.

    PubMed

    Kanayama, Gen; Pope, Harrison G; Cohane, Geoffrey; Hudson, James I

    2003-07-20

    Anabolic-androgenic steroid (AAS) use represents a major public health problem in the United States, but the risk factors for this form of drug use are little studied. We evaluated 48 men who had used AAS for at least 2 months and 45 men who had never used AAS, using a verbal interview and a battery of questionnaires covering hypothesized demographic, familial, and psychosocial risk factors for AAS use. All subjects in both groups were experienced weightlifters; thus, differences between groups were likely to be associated specifically with AAS use, rather than with weightlifting in general. The AAS users and non-users generally described similar childhood and family experiences, but users reported significantly poorer relationships with their fathers and greater childhood conduct disorder than non-users. At the time that they first started lifting weights, AAS users and non-users were similar in their perceived physical, social, and sexual status, but users were significantly less confident about their body appearance. AAS users displayed much higher rates of other illicit substance use, abuse, or dependence than non-users, with use of other illicit substances almost always preceding first use of AAS. These findings suggest that AAS use may be most likely to occur in men with high levels of antisocial traits and low levels of body esteem.

  7. Anabolic steroids.

    PubMed

    Mottram, D R; George, A J

    2000-03-01

    Anabolic steroids are synthetic derivatives of testosterone modified to enhance the anabolic rather than the androgenic actions of the hormone. The anabolic effects are considered to be those promoting protein synthesis, muscle growth and crythopoiesis. There are numerous side-effects to anabolic steroids, including hypertension and atherosclerosis, blood clotting, jaundice, hepatic carcinoma, tendon damage, psychiatric and behavioural effects and, in males, reduced fertility and gynaccomastia. Anabolic steroids were added to the International Olympic Committee's list of banned substances in 1975. The majority of 'evidence' concerning the efficacy of anabolic steroids as performance enhancing agents is anecdotal. In the main, experimental investigations have been poorly designed scientifically, clinically and statistically. The percentage of positive test results from IOC accredited laboratories has remained consistently low. However, athletes take their steroids during training and out-of-competition testing is not conducted in all countries, although international co-operation is now under consideration. Despite the lack of conclusive evidence, steroids users will continue to hold the view that their effects are efficacious and they are therefore unlikely to be persuaded to curtail their use.

  8. Epidermal growth factor receptor plays an anabolic role in bone metabolism in vivo.

    PubMed

    Zhang, Xianrong; Tamasi, Joseph; Lu, Xin; Zhu, Ji; Chen, Haiyan; Tian, Xiaoyan; Lee, Tang-Cheng; Threadgill, David W; Kream, Barbara E; Kang, Yibin; Partridge, Nicola C; Qin, Ling

    2011-05-01

    While the epidermal growth factor receptor (EGFR)-mediated signaling pathway has been shown to have vital roles in many developmental and pathologic processes, its functions in the development and homeostasis of the skeletal system has been poorly defined. To address its in vivo role, we constructed transgenic and pharmacologic mouse models and used peripheral quantitative computed tomography (pQCT), micro-computed tomography (µCT) and histomorphometry to analyze their trabecular and cortical bone phenotypes. We initially deleted the EGFR in preosteoblasts/osteoblasts using a Cre/loxP system (Col-Cre Egfr(f/f)), but no bone phenotype was observed because of incomplete deletion of the Egfr genomic locus. To further reduce the remaining osteoblastic EGFR activity, we introduced an EGFR dominant-negative allele, Wa5, and generated Col-Cre Egfr(Wa5/f) mice. At 3 and 7 months of age, both male and female mice exhibited a remarkable decrease in tibial trabecular bone mass with abnormalities in trabecular number and thickness. Histologic analyses revealed decreases in osteoblast number and mineralization activity and an increase in osteoclast number. Significant increases in trabecular pattern factor and structural model index indicate that trabecular microarchitecture was altered. The femurs of these mice were shorter and smaller with reduced cortical area and periosteal perimeter. Moreover, colony-forming unit-fibroblast (CFU-F) assay indicates that these mice had fewer bone marrow mesenchymal stem cells and committed progenitors. Similarly, administration of an EGFR inhibitor into wild-type mice caused a significant reduction in trabecular bone volume. In contrast, Egfr(Dsk5/+) mice with a constitutively active EGFR allele displayed increases in trabecular and cortical bone content. Taken together, these data demonstrate that the EGFR signaling pathway is an important bone regulator and that it primarily plays an anabolic role in bone metabolism.

  9. Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment

    PubMed Central

    Aini, Hailati; Itaka, Keiji; Fujisawa, Ayano; Uchida, Hirokuni; Uchida, Satoshi; Fukushima, Shigeto; Kataoka, Kazunori; Saito, Taku; Chung, Ung-il; Ohba, Shinsuke

    2016-01-01

    Osteoarthritis (OA) is a chronic degenerative joint disease and a major health problem in the elderly population. No disease-modifying osteoarthritis drug (DMOAD) has been made available for clinical use. Here we present a disease-modifying strategy for OA, focusing on messenger RNA (mRNA) delivery of a therapeutic transcription factor using polyethylene glycol (PEG)-polyamino acid block copolymer-based polyplex nanomicelles. When polyplex nanomicelles carrying the cartilage-anabolic, runt-related transcription factor (RUNX) 1 mRNA were injected into mouse OA knee joints, OA progression was significantly suppressed compared with the non-treatment control. Expressions of cartilage-anabolic markers and proliferation were augmented in articular chondrocytes of the RUNX1-injected knees. Thus, this study provides a proof of concept of the treatment of degenerative diseases such as OA by the in situ mRNA delivery of therapeutic transcription factors; the presented approach will directly connect basic findings on disease-protective or tissue-regenerating factors to disease treatment. PMID:26728350

  10. Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment.

    PubMed

    Aini, Hailati; Itaka, Keiji; Fujisawa, Ayano; Uchida, Hirokuni; Uchida, Satoshi; Fukushima, Shigeto; Kataoka, Kazunori; Saito, Taku; Chung, Ung-il; Ohba, Shinsuke

    2016-01-05

    Osteoarthritis (OA) is a chronic degenerative joint disease and a major health problem in the elderly population. No disease-modifying osteoarthritis drug (DMOAD) has been made available for clinical use. Here we present a disease-modifying strategy for OA, focusing on messenger RNA (mRNA) delivery of a therapeutic transcription factor using polyethylene glycol (PEG)-polyamino acid block copolymer-based polyplex nanomicelles. When polyplex nanomicelles carrying the cartilage-anabolic, runt-related transcription factor (RUNX) 1 mRNA were injected into mouse OA knee joints, OA progression was significantly suppressed compared with the non-treatment control. Expressions of cartilage-anabolic markers and proliferation were augmented in articular chondrocytes of the RUNX1-injected knees. Thus, this study provides a proof of concept of the treatment of degenerative diseases such as OA by the in situ mRNA delivery of therapeutic transcription factors; the presented approach will directly connect basic findings on disease-protective or tissue-regenerating factors to disease treatment.

  11. Extended key-factor/key-stage analysis for longitudinal data.

    PubMed

    Yamamura, Kohji

    2012-01-01

    Key-factor/key-stage analysis was originally a descriptive approach to analyze life tables. However, this method can be extended to analyze longitudinal data in pharmaceutical experiments. By dividing the variance into components, the extended key-factor/key-stage analysis indicates which factor is influential, and through which stage the factor generates its influence in determining the outcome of treatments. Such knowledge helps us in constructing a class of nonlinear longitudinal models that can be interpretable than linear models. Example SAS programs and R programs are provided for the calculation. Supplemental materials are available for this article. Go to the publisher's online edition of Journal of Biopharmaceutical Statistics to view the supplemental files.

  12. Pharmacology of anabolic steroids.

    PubMed

    Kicman, A T

    2008-06-01

    Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic-androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided.

  13. Medical Issues Associated with Anabolic Steroid Use: Are They Exaggerated?

    PubMed Central

    Hoffman, Jay R.; Ratamess, Nicholas A.

    2006-01-01

    For the past 50 years anabolic steroids have been at the forefront of the controversy surrounding performance enhancing drugs. For almost half of this time no attempt was made by sports governing bodies to control its use, and only recently have all of the major sports governing bodies in North America agreed to ban from competition and punish athletes who test positive for anabolic steroids. These punitive measures were developed with the primary concern for promotion of fair play and eliminating potential health risks associated with androgenic-anabolic steroids. Yet, controversy exists whether these testing programs deter anabolic steroid use. Although the scope of this paper does not focus on the effectiveness of testing, or the issue of fair play, it is of interest to understand why many athletes underestimate the health risks associated from these drugs. What creates further curiosity is the seemingly well-publicized health hazards that the medical community has depicted concerning anabolic steroidabuse. Is there something that the athletes know, or are they simply naïve regarding the dangers? The focus of this review is to provide a brief history of anabolic steroid use in North America, the prevalence of its use in both athletic and recreational populations and its efficacy. Primary discussion will focus on health issues associated with anabolic steroid use with an examination of the contrasting views held between the medical community and the athletes that are using these ergogenic drugs. Existing data suggest that in certain circumstances the medical risk associated with anabolic steroid use may have been somewhat exaggerated, possibly to dissuade use in athletes. Key Points For many years the scientific and medical communities depicted a lack of efficacy and serious adverse effects from anabolic steroid use. Clinical case studies continue to link anabolic steroid administration with myocardial infarct, suicide, and cancer, evidence to support a cause

  14. Medical issues associated with anabolic steroid use: are they exaggerated?

    PubMed

    Hoffman, Jay R; Ratamess, Nicholas A

    2006-01-01

    For the past 50 years anabolic steroids have been at the forefront of the controversy surrounding performance enhancing drugs. For almost half of this time no attempt was made by sports governing bodies to control its use, and only recently have all of the major sports governing bodies in North America agreed to ban from competition and punish athletes who test positive for anabolic steroids. These punitive measures were developed with the primary concern for promotion of fair play and eliminating potential health risks associated with androgenic-anabolic steroids. Yet, controversy exists whether these testing programs deter anabolic steroid use. Although the scope of this paper does not focus on the effectiveness of testing, or the issue of fair play, it is of interest to understand why many athletes underestimate the health risks associated from these drugs. What creates further curiosity is the seemingly well-publicized health hazards that the medical community has depicted concerning anabolic steroidabuse. Is there something that the athletes know, or are they simply naïve regarding the dangers? The focus of this review is to provide a brief history of anabolic steroid use in North America, the prevalence of its use in both athletic and recreational populations and its efficacy. Primary discussion will focus on health issues associated with anabolic steroid use with an examination of the contrasting views held between the medical community and the athletes that are using these ergogenic drugs. Existing data suggest that in certain circumstances the medical risk associated with anabolic steroid use may have been somewhat exaggerated, possibly to dissuade use in athletes. Key PointsFor many years the scientific and medical communities depicted a lack of efficacy and serious adverse effects from anabolic steroid use.Clinical case studies continue to link anabolic steroid administration with myocardial infarct, suicide, and cancer, evidence to support a cause and

  15. Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone

    NASA Technical Reports Server (NTRS)

    Bikle, Daniel D.; Sakata, Takeshi; Leary, Colin; Elalieh, Hashem; Ginzinger, David; Rosen, Clifford J.; Beamer, Wesley; Majumdar, Sharmila; Halloran, Bernard P.

    2002-01-01

    Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 microg/kg) or vehicle for 2 weeks after which their tibias were examined for fat-free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF-I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several-fold more in response to PTH than the mRNAs in the bones from their wild-type littermates. These results indicate that IGF-I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH.

  16. Validation of commercial ELISAs for quantifying anabolic growth factors and cytokines in canine ACD-A anticoagulated plasma.

    PubMed

    Birdwhistell, Kate; Basinger, Robert; Hayes, Brian; Norton, Natalie; Hurley, David J; Franklin, Samuel P

    2017-03-01

    Platelet-rich plasma has been studied extensively in dogs, but validation of enzyme-linked immunosorbent assays (ELISAs) for quantifying anabolic growth factors and inflammatory cytokines in canine plasma prepared with citrate-based anticoagulants is not available. We performed a validation of commercial ELISAs for transforming growth factor-beta 1 (TGF-β1), platelet-derived growth factor-BB (PDGF-BB), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) for use with canine plasma prepared with acid-citrate-dextrose, solution A (ACD-A). Platelet-poor plasma (PPP) anticoagulated with ACD-A as well as PPP anticoagulated with ACD-A and spiked with the relevant canine recombinant proteins were evaluated with each ELISA to calculate the efficiency of spike recovery. Replicates of the spiked PPP were also assessed in 2 additional assays to quantify intra-assay and interassay precision. The efficiency of spike recovery was within 75-125% of the expected concentration for the TGF-β1, PDGF-BB, and VEGF ELISAs. The intra- and interassay variability were <25% for the TGF-β1, PDGF-BB, VEGF, and TNF-α ELISAs. The TGF-β1, PDGF-BB, and VEGF ELISAs demonstrate acceptable efficiency of spike recovery and intra- and interassay variability, whereas the TNF-α and IL-1β ELISAs did not meet industry standards of performance with ACD-A anticoagulated canine plasma.

  17. Pharmacology of anabolic steroids

    PubMed Central

    Kicman, A T

    2008-01-01

    Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic–androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided. PMID:18500378

  18. Anabolic steroid accelerated multicompartment syndrome following trauma

    PubMed Central

    Bahia, H; Platt, A; Hart, N; Baguley, P

    2000-01-01

    The case is reported of a 23 year old male body builder who was involved in a road traffic accident after taking anabolic steroids. The resulting trauma caused a severe life threatening acute multicompartment syndrome resulting in the need for urgent multiple fasciotomies. Key Words: anabolic steroids; body builder; trauma; multicompartment syndrome PMID:10953907

  19. Anabolic steroids.

    PubMed

    Brower, K J

    1993-03-01

    Anabolic-androgenic steroids are controlled substances that are taken illicitly to enhance physical appearance and performance. In addition to the desired somatic effects, reasonably good evidence suggests that AASs are capable of influencing mood and behavior. A myriad of adverse effects have been reported. Although many of these effects appear to reverse with cessation of use, fatalities due to suicides, homicides, liver disease, heart attacks, and cancer have been reported infrequently among illicit users. Although studies are needed to quantify more precisely the long-term consequences and risks of using AASs, patterns of illicit use are particularly troublesome. The use of extremely high doses, needles, counterfeit and veterinary drugs, and multiple steroidal and nonsteroidal drugs simultaneously may further enhance the risks of using AASs. The clinician should suspect AAS use in high-risk individuals who manifest any of the possible consequences described in this article. Laboratory tests can be valuable for detection of use and assessment of consequences. Treatment approaches may borrow from proven techniques employed with other substance abusers, but should also address the special value that physical attributes and body image have for the AAS user.

  20. T cells, osteoblasts, and osteocytes: interacting lineages key for the bone anabolic and catabolic activities of parathyroid hormone.

    PubMed

    Pacifici, Roberto

    2016-01-01

    Osteoimmunology is a field of research dedicated to the study of the interactions between the immune system and bone. Among the cells of the immune system that regulate bone turnover and the responsiveness of bone cells to calciothropic hormones are bone marrow T lymphocytes. T cells secrete osteoclastogenic cytokines such as RANKL and TNF-α, as well as factors that stimulate bone formation, one of which is Wnt10b. In addition, T cells regulate the differentiation and life span of stromal cells (SCs) and their responsiveness to parathyroid hormone (PTH) via costimulatory molecules expressed on their surface. The conditioning effect of T cells on SCs is inherited by the osteoblastic and osteocytic progeny of SCs. As a result, osteoblastic cells of T cell-deficient mice have functional characteristics different from corresponding cells of T cell-replete mice. These differences include the ratio of RANKL/OPG produced in response to continuous PTH treatment, and the osteoblastogenic response to intermittent PTH treatment. This article reviews the evidence indicating that the effects of PTH are mediated not only by osteoblasts and osteocytes but also by T cells.

  1. T cells, osteoblasts, and osteocytes: interacting lineages key for the bone anabolic and catabolic activities of parathyroid hormone

    PubMed Central

    Pacifici, Roberto

    2015-01-01

    Osteoimmunology is field of research dedicated to the study of the interactions between the immune system and bone. Among the cells of the immune system that regulate bone turnover and the responsiveness of bone cells to calciothropic hormones are bone marrow T lymphocytes. T cells secrete osteoclastogenic cytokines such as RANKL and TNF-α, as well as factors that stimulate bone formation, one of which is Wnt10b. In addition, T cells regulate the differentiation and life span of stromal cells and their responsiveness to parathyroid hormone (PTH) via costimulatory molecules expressed on their surface. The conditioning effect of T cells on stromal cells (SCs) is inherited by the osteoblastic and osteocytic progeny of SCs. As a result, osteoblastic cells of T cell–deficient mice have functional characteristics different from corresponding cells of T cell–replete mice. These differences include the ratio of RANKL/OPG produced in response to continuous PTH treatment, and the osteoblastogenic response to intermittent PTH treatment. This article reviews the evidence indicating that the effects of parathyroid hormone are mediated not only by osteoblasts and osteocytes but also by T cells. PMID:26662934

  2. Androgenic anabolic steroids also impair right ventricular function.

    PubMed

    Kasikcioglu, Erdem; Oflaz, Huseyin; Umman, Berrin; Bugra, Zehra

    2009-05-01

    Chronic anabolic steroid use suppresses left ventricular functions. However, there is no information regarding the chronic effects of anabolic steroids on right ventricular function which also plays a key role in global cardiac function. The main objective of the present study was to investigate the effects of androgenic anabolic steroids usage among athletes on remodeling the right part of the heart. Androgenic-anabolic steroids-using bodybuilders had smaller diastolic velocities of both ventricles than drug-free bodybuilders and sedentary counterparts. This study shows that androgenic anabolic steroids-using bodybuilders exhibited depressed diastolic functions of both ventricles.

  3. Chronic Anabolic Androgenic Steroid Exposure Alters Corticotropin Releasing Factor Expression and Anxiety-Like Behaviors in the Female Mouse

    PubMed Central

    Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

    2010-01-01

    Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

  4. Chronic anabolic androgenic steroid exposure alters corticotropin releasing factor expression and anxiety-like behaviors in the female mouse.

    PubMed

    Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

    2010-11-01

    In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central nucleus of the amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BnST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST.

  5. Corticotropin-Releasing Factor Modulation of Forebrain GABAergic Transmission has a Pivotal Role in the Expression of Anabolic Steroid-Induced Anxiety in the Female Mouse

    PubMed Central

    Oberlander, Joseph G; Henderson, Leslie P

    2012-01-01

    Increased anxiety is commonly observed in individuals who illicitly administer anabolic androgenic steroids (AAS). Behavioral effects of steroid abuse have become an increasing concern in adults and adolescents of both sexes. The dorsolateral bed nucleus of the stria terminalis (dlBnST) has a critical role in the expression of diffuse anxiety and is a key site of action for the anxiogenic neuromodulator, corticotropin releasing factor (CRF). Here we demonstrate that chronic, but not acute, exposure of female mice during adolescence to AAS augments anxiety-like behaviors; effects that were blocked by central infusion of the CRF receptor type 1 antagonist, antalarmin. AAS treatment selectively increased action potential (AP) firing in neurons of the central amygdala (CeA) that project to the dlBnST, increased the frequency of GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in dlBnST target neurons, and decreased both c-FOS immunoreactivity (IR) and AP frequency in these postsynaptic cells. Acute application of antalarmin abrogated the enhancement of GABAergic inhibition induced by chronic AAS exposure whereas application of CRF to brain slices of naïve mice mimicked the actions of this treatment. These results, in concert with previous data demonstrating that chronic AAS treatment results in enhanced levels of CRF mRNA in the CeA and increased CRF-IR in the dlBnST neuropil, are consistent with a mechanism in which the enhanced anxiety elicited by chronic AAS exposure involves augmented inhibitory activity of CeA afferents to the dlBnST and CRF-dependent enhancement of GABAergic inhibition in this brain region. PMID:22298120

  6. SARS: Key factors in crisis management.

    PubMed

    Tseng, Hsin-Chao; Chen, Thai-Form; Chou, Shieu-Ming

    2005-03-01

    This study was conducted at a single hospital selected in Taipei during the SARS (Severe Acute Respiratory Syndrome) outbreak from March to July, 2003 in Taiwan. During this period of time, 104 SARS patients were admitted to the hospital. There were no negative reports related to the selected hospital despite its being located right in the center of an area struck by the epidemic. The purpose of this study was to identify the key factors enabling the hospital to survive SARS unscathed. Data were collected from in-depth interviews with the nursing directors and nursing managers of the SARS units, along with a review of relevant hospital documents. The five key elements identified as survival factors during this SARS crisis are as follows: 1. good control of timing for crisis management, 2. careful decision-making, 3. thorough implementation, 4. effective communication, and 5. trust between management and employees. The results of this study reconfirmed the selected hospital as a model for good crisis management during the SARS epidemic.

  7. Helicopter training simulators: Key market factors

    NASA Technical Reports Server (NTRS)

    Mcintosh, John

    1992-01-01

    Simulators will gain an increasingly important role in training helicopter pilots only if the simulators are of sufficient fidelity to provide positive transfer of skills to the aircraft. This must be done within an economic model of return on investment. Although rotor pilot demand is still only a small percentage of overall pilot requirements, it will grow in significance. This presentation described the salient factors influencing the use of helicopter training simulators.

  8. Mind Over Matter: Anabolic Steroids

    MedlinePlus

    ... Matter Teaching Guide and Series / Anabolic Steroids Print Mind Over Matter: Anabolic Steroids Order Free Publication in: ... how drugs affect the brain and nervous system. Mind Over Matter is produced by the National Institute ...

  9. Anabolic Steroids (For Teens)

    MedlinePlus

    ... typically spend a large amount of time and money obtaining the drugs, another sign they could be addicted. When they ... get more information? Drug Facts NIDA: Commonly Abused Drugs Chart DrugFacts: ... Report Series: Anabolic Steroid Abuse Statistics and Trends ...

  10. Key systemic and environmental risk factors for implant failure.

    PubMed

    Dawson, Dolphus R; Jasper, Samuel

    2015-01-01

    Dental implants are an important treatment option for patients interested in replacing lost or missing teeth. Although a robust body of literature has reviewed risk factors for tooth loss, the evidence for risk factors associated with dental implants is less well defined. This article focuses on key systemic risk factors relating to dental implant failure, as well as on perimucositis and peri-implantitis.

  11. The Misuse of Anabolic-Androgenic Steroids among Iranian Recreational Male Body-Builders and Their Related Psycho-Socio-Demographic factors

    PubMed Central

    ANGOORANI, Hooman; HALABCHI, Farzin

    2015-01-01

    Background: The high prevalence and potential side effects of anabolic-androgenic steroids (AAS) misuse by athletes has made it a major public health concern. Epidemiological studies on the abuse of such drugs are mandatory for developing effective preventive drug control programs in sports community. This study aimed to investigate the prevalence of AAS abuse and their association with some psycho-socio-demographic factors in Iranian male recreational body-builders. Methods: Between March and October 2011; 906 recreational male body-builders from 103 randomly selected bodybuilding clubs in Tehran, Iran were participated in this study. Some psycho-socio- demographic factors including age, job, average family income, family size, sport experience (months), weekly duration of the sporting activity (h), purpose of participation in sporting activity, mental health as well as body image (via General Health Questionnaire and Multidimensional Body-Self Relations Questionnaire, respectively), and history of AAS use were obtained by interviews using questionnaires. Results: Participants were all recreational male body-builders [mean age (SD): 25.7 (7.1), ranging 14–56 yr]. Self-report of AAS abuse was registered in 150 body-builders (16.6%). Among different psycho-socio-demographic factors, only family income and sport experience were inversely associated with AAS abuse. Conclusion: Lifetime prevalence of AAS abuse is relatively high among recreational body-builders based on their self-report. Some psycho-socio-demographic factors including family income and sport experience may influence the prevalence of AAS abuse. PMID:26811817

  12. Mad men, women and steroid cocktails: A review of the impact of sex and other factors on anabolic androgenic steroids effects on affective behaviors

    PubMed Central

    Henderson, Leslie P.

    2016-01-01

    Rationale For several decades, elite athletes and a growing number of recreational consumers have used anabolic androgenic steroids (AAS) as performance enhancing drugs. Despite mounting evidence that illicit use of these synthetic steroids has detrimental effects on affective states, information available on sex-specific actions of these drugs is lacking. Objectives The focus of this review is to assess information to date on the importance of sex and its interaction with other environmental factors on affective behaviors, with an emphasis on data derived from non-human studies. Methods The PubMed database was searched for relevant studies in both sexes. Results Studies examining AAS use in females are limited, reflecting the lower prevalence of use in this sex. Data, however, indicate significant sex-specific differences in AAS effects on anxiety-like and aggressive behaviors, interactions with other drugs of abuse, and the interplay of AAS with other environmental factors such as diet and exercise. Conclusions Current methods for assessing AAS use have limitations that suggest biases of both under- and over-reporting, which may be amplified for females who are poorly represented in self-report studies of human subjects and are rarely used in animal studies. Data from animal literature suggest that there are significant sex-specific differences in the impact of AAS on aggression, anxiety, and concomitant use of other abused substances. These results have relevance for human females who take these drugs as performance enhancing substances and for transgender XX individuals who may illicitly self-administer AAS as they transition to a male gender identity. PMID:26758282

  13. Desire: A Key Factor for Successful Online GED Adult Learners

    ERIC Educational Resources Information Center

    Shaw, Donita; Tham, Yuen San Sarah; Hogle, Julie; Koch, Jody

    2015-01-01

    The purpose of this study was to analyze the experiences of 12 adult online General Educational Development (GED) students to determine the role of program and personal factors that influenced their successful passing of the GED or their dropping-out of the program. Through surveys and interviews, we discovered that desire was the key factor for…

  14. Physiological and isotopic characteristics of nitrogen fixation by hyperthermophilic methanogens: Key insights into nitrogen anabolism of the microbial communities in Archean hydrothermal systems

    NASA Astrophysics Data System (ADS)

    Nishizawa, Manabu; Miyazaki, Junichi; Makabe, Akiko; Koba, Keisuke; Takai, Ken

    2014-08-01

    Hyperthermophilic hydrogenotrophic methanogens are considered to be one of the most predominant primary producers in hydrogen (H2)-abundant hydrothermal environments in the present-day ocean and throughout the history of the Earth. However, the nitrogen sources supporting the development of microbial communities in hydrothermal environments remain poorly understood. We have investigated, for the first time, methanogenic archaea commonly found in deep-sea hydrothermal environments to understand their physiological properties (growth kinetics, energetics, and metal requirements) and isotopic characteristics during the fixation of dinitrogen (N2), which is an abundant but less-bioavailable compound in hydrothermal fluids. Culture experiments showed that Methanocaldococcus strain (Mc 1-85N) (Topt = 85 °C) and Methanothermococcus strain (Mt 5-55N) (Topt = 55 °C) assimilated N2 and ammonium, but not nitrate. Previous phylogenetic studies have predicted that the Methanocaldococcus and Methanothermococcus lineages have nitrogenases, key enzymes for N2 fixation, with biochemically uncharacterised active site metal cofactors. We showed that Mt 5-55N required molybdenum for the nitrogenase to function, implying a molybdenum-bearing cofactor in the strain. Molybdenum also stimulated diazotrophic (i.e., N2-fixing) growth of Mc 1-85N, though further experiments are required to test whether the strain contains a molybdenum-dependent nitrogenase. Importantly, Mc 1-85N exhibited an apparently lower requirement of and higher tolerance to molybdenum and iron than Mt 5-55N. Furthermore, both strains produced more 15N-depleted biomass (-4‰ relative to N2) than that previously reported for diazotrophic photosynthetic prokaryotes. These results demonstrate that diazotrophic hyperthermophilic methanogens can be broadly distributed in seafloor and subseafloor hydrothermal environments, where the availability of transition metals is variable and where organic carbon, organic nitrogen

  15. Metabolic remodeling of the tumor microenvironment: migration stimulating factor (MSF) reprograms myofibroblasts toward lactate production, fueling anabolic tumor growth.

    PubMed

    Carito, Valentina; Bonuccelli, Gloria; Martinez-Outschoorn, Ubaldo E; Whitaker-Menezes, Diana; Caroleo, Maria Cristina; Cione, Erika; Howell, Anthony; Pestell, Richard G; Lisanti, Michael P; Sotgia, Federica

    2012-09-15

    Migration stimulating factor (MSF) is a genetically truncated N-terminal isoform of fibronectin that is highly expressed during mammalian development in fetal fibroblasts, and during tumor formation in human cancer-associated myofibroblasts. However, its potential functional role in regulating tumor metabolism remains unexplored. Here, we generated an immortalized fibroblast cell line that recombinantly overexpresses MSF and studied their properties relative to vector-alone control fibroblasts. Our results indicate that overexpression of MSF is sufficient to confer myofibroblastic differentiation, likely via increased TGF-b signaling. In addition, MSF activates the inflammation-associated transcription factor NFκB, resulting in the onset of autophagy/mitophagy, thereby driving glycolytic metabolism (L-lactate production) in the tumor microenvironment. Consistent with the idea that glycolytic fibroblasts fuel tumor growth (via L-lactate, a high-energy mitochondrial fuel), MSF fibroblasts significantly increased tumor growth, by up to 4-fold. Mechanistic dissection of the MSF signaling pathway indicated that Cdc42 lies downstream of MSF and fibroblast activation. In accordance with this notion, Cdc42 overexpression in immortalized fibroblasts was sufficient to drive myofibroblast differentiation, to provoke a shift towards glycolytic metabolism and to promote tumor growth by up to 2-fold. In conclusion, the MSF/Cdc42/NFκB signaling cascade may be a critical druggable target in preventing "Warburg-like" cancer metabolism in tumor-associated fibroblasts. Thus, MSF functions in the metabolic remodeling of the tumor microenvironment by metabolically reprogramming cancer-associated fibroblasts toward glycolytic metabolism.

  16. Anabolic steroid boosts weight.

    PubMed

    1996-09-01

    A randomized study of nandrolone decanoate (Deca-Durabolin) showed that the anabolic steroid can increase weight in people with HIV infections. The group receiving nandrolone experienced a greater increase both in fat-free mass and body cell mass (although the latter measure did not reach statistical significance) than those on placebo. Deca-Durabolin had little to do with two occurrences of Kaposi's sarcoma (KS) in the study group, but until further studies are completed, caution is advised when using this steroid in patients with KS. A new study comparing nandrolone to growth hormone in patients with wasting is slated to begin in the next 3 or 4 months.

  17. Test methods: anabolics.

    PubMed

    Saugy, M; Cardis, C; Robinson, N; Schweizer, C

    2000-03-01

    In the International Olympic Committee (IOC) accredited laboratories, specific methods have been developed to detect anabolic steroids in athletes' urine. The technique of choice to achieve this is gas-chromatography coupled with mass spectrometry (GC-MS). In order to improve the efficiency of anti-doping programmes, the laboratories have defined new analytical strategies. The final sensitivity of the analytical procedure can be improved by choosing new technologies for use in detection, such as tandem mass spectrometry (MS-MS) or high resolution mass spectrometry (HRMS). A better sample preparation using immuno-affinity chromatography (IAC) is also a good tool for improving sensitivity. These techniques are suitable for the detection of synthetic anabolic steroids whose structure is not found naturally in the human body. The more and more evident use, on a large scale, of substances chemically similar to the endogenous steroids obliges both the laboratory and the sports authorities to use the steroid profile of the athlete in comparison with reference ranges from a population or with intraindividual reference values.

  18. Graduate Entrepreneurship Incubation Environments: A Framework of Key Success Factors

    ERIC Educational Resources Information Center

    Al-Dajani, Haya; Dedoussis, Evangelos; Watson, Erika; Tzokas, Nikalaos

    2014-01-01

    The benchmarking framework developed in this study is specifically designed for higher education institutions to consider when developing environments to encourage entrepreneurship among their students, graduates and staff. The objective of the study was to identify key success factors of Graduate Entrepreneurship Incubator Environments (GEIEs)…

  19. Anabolic Steroids...What's the Hype?...

    ERIC Educational Resources Information Center

    Landry, Gregory L.; Wagner, Lauris L.

    This pamphlet uses a question-and-answer format to examine the use and abuse of anabolic steroids. It begins by explaining that all steroids are not anabolic steroids and that anabolic steroids are those used specifically to build muscles quickly. Medical uses of anabolic steroids are reviewed; how people get steroids, how they take them, and…

  20. The anabolic effects of vitamin D-binding protein-macrophage activating factor (DBP-MAF) and a novel small peptide on bone.

    PubMed

    Schneider, Gary B; Grecco, Kristina J; Safadi, Fayez F; Popoff, Steven N

    2003-01-01

    Vitamin D-binding protein-macrophage activating factor (DBP-MAF) has previously been shown to stimulate bone resorption and correct the skeletal defects associated with osteopetrosis in two nonallelic mutations in rats. This same protein and a small fragment of the protein have now been shown to demonstrate an anabolic effect on the skeleton of both newborn and young adult, intact rats. The novel peptide fragment was synthetically produced based on the human amino acid sequence at the site of glycosylation in the third domain of the native protein (DBP). The peptide tested is 14 amino acids in length and demonstrates no homologies other than to that region of DBP. Newborn rats were injected i.p. with saline, peptide (0.4 ng/g body wt.) or DBP-MAF (2 ng/g body wt.) every other day from birth to 14 days of age. On day 16 the rats were euthanized and the long bones collected for bone densitometry by pQCT. After 2 weeks of treatment with either the whole protein (DBP-MAF) or the small peptide, bone density was significantly increased in the treated animals compared to the saline controls. Young adult female rats (180 grams) were given s.c. injections of saline or peptide (0.4 ng/g body wt. or 5 ng/g body wt.) every other day for 2 weeks; 2 days after the final injections, the rats were euthanized and the femurs and tibias collected for bone densitometry. Both doses of the peptide resulted in significant increases in bone density as determined by pQCT. Young adult rats were injected locally with a single dose of the peptide (1 microg) or saline into the marrow cavity of the distal femur. One week after the single injection, the bones were collected for radiographic and histological evaluation. The saline controls showed no evidence of new bone formation, whereas the peptide-treated animals demonstrated osteoinduction in the marrow cavity and osteogenesis of surrounding cortical and metaphyseal bone. These data suggest that DBP-MAF and the synthetic peptide represent

  1. Faculty perceptions of key factors in interprofessional education.

    PubMed

    Loversidge, Jacqueline; Demb, Ada

    2015-01-01

    Embedding interprofessional education (IPE) into academic programs presents structural, curricular and human factor challenges. Nurses and physicians comprise the dominant dyad in healthcare, and therefore nursing and medical faculty are key in guiding future IPE approaches. However, faculty experiences with IPE are rarely reported. This paper presents perceptions of medical and nursing faculty about key factors related to IPE for pre-licensure medical and nursing students. Semi-structured interviews with 32 faculty from three Midwest universities were analyzed thematically in this phenomenological study based on collaboration and cooperation theories. Findings clustered into six categories. Specific subthemes little discussed in the literature are addressed in detail. Study participants felt the most powerful interprofessional student experiences were authentic and faculty-facilitated, that constructive clinical environments were crucial, that curriculum design challenges included disparities between undergraduate and graduate education, and that leadership commitment to full-time and adjunct faculty engagement and development was imperative.

  2. From shared care to disease management: key-influencing factors

    PubMed Central

    Eijkelberg, Irmgard M.J.G.; Spreeuwenberg, Cor; Mur-Veeman, Ingrid M.; Wolffenbuttel, Bruce H.R.

    2001-01-01

    Abstract Background In order to improve the quality of care of chronically ill patients the traditional boundaries between primary and secondary care are questioned. To demolish these boundaries so-called ‘shared care’ projects have been initiated in which different ways of substitution of care are applied. When these projects end, disease management may offer a solution to expand the achieved co-operation between primary and secondary care. Objective Answering the question: What key factors influence the development and implementation of shared care projects from a management perspective and how are they linked? Theory The theoretical framework is based on the concept of the learning organisation. Design Reference point is a multiple case study that finally becomes a single case study. Data are collected by means of triangulation. The studied cases concern two interrelated Dutch shared care projects for type 2 diabetic patients, that in the end proceed as one disease management project. Results In these cases the predominant key-influencing factors appear to be the project management, commitment and local context, respectively. The factor project management directly links the latter two, albeit managing both appear prerequisites to its success. In practice this implies managing the factors' interdependency by the application of change strategies and tactics in a committed and skilful way. Conclusion Project management, as the most important and active key factor, is advised to cope with the interrelationships of the influencing factors in a gradually more fundamental way by using strategies and tactics that enable learning processes. Then small-scale shared care projects may change into a disease management network at a large scale, which may yield the future blueprint to proceed. PMID:16896415

  3. Protein Anabolic Resistance in Cancer: Does it really exist?

    PubMed Central

    Engelen, Mariëlle P. K. J.; van der Meij, Barbara S.; Deutz, Nicolaas E. P.

    2016-01-01

    Purpose of review Preventing unintentional weight and muscle loss is of crucial importance to maintain the condition and well-being of patients with cancer, improve treatment response and tolerance, and prolong survival. Anabolic resistance might explain why some cancer patients do not respond to nutritional intervention but does recent evidence actually support this? We will discuss recent literature that cast doubt on attenuated anabolic potential in cancer. Recent findings Although anabolic resistance was observed in the past, more recent studies have shown that advanced cancer patients have an anabolic potential after intake of high-quality proteins. Furthermore a consistent linear relationship is observed in cancer between (essential) amino acid availability from the diet and net protein gain. The studied cancer patients however were often characterized by a normal or obese body weight, following the trend in the general population, and mild systemic inflammation. Factors like recent chemotherapy, surgery or cachexia do not seem to attenuate the anabolic potential to feeding. Summary Cancer patients have a normal anabolic potential which relates to the amount of essential amino acids in the meal. It remains to be determined if this is also the case in weak cancer patients with a short life expectancy and high systemic inflammation. PMID:26560520

  4. Cardiac effects of anabolic steroids

    PubMed Central

    Payne, J R; Kotwinski, P J; Montgomery, H E

    2004-01-01

    Anabolic steroid abuse in athletes has been associated with a wide range of adverse conditions, including hypogonadism, testicular atrophy, impaired spermatogenesis, gynaecomastia, and psychiatric disturbance. But what effect does steroid abuse have on the cardiovascular system? PMID:15084526

  5. Five key factors determining pairwise correlations in visual cortex

    PubMed Central

    Sahani, Maneesh; Carandini, Matteo

    2015-01-01

    The responses of cortical neurons to repeated presentation of a stimulus are highly variable, yet correlated. These “noise correlations” reflect a low-dimensional structure of population dynamics. Here, we examine noise correlations in 22,705 pairs of neurons in primary visual cortex (V1) of anesthetized cats, during ongoing activity and in response to artificial and natural visual stimuli. We measured how noise correlations depend on 11 factors. Because these factors are themselves not independent, we distinguished their influences using a nonlinear additive model. The model revealed that five key factors play a predominant role in determining pairwise correlations. Two of these are distance in cortex and difference in sensory tuning: these are known to decrease correlation. A third factor is firing rate: confirming most earlier observations, it markedly increased pairwise correlations. A fourth factor is spike width: cells with a broad spike were more strongly correlated amongst each other. A fifth factor is spike isolation: neurons with worse isolation were more correlated, even if they were recorded on different electrodes. For pairs of neurons with poor isolation, this last factor was the main determinant of correlations. These results were generally independent of stimulus type and timescale of analysis, but there were exceptions. For instance, pairwise correlations depended on difference in orientation tuning more during responses to gratings than to natural stimuli. These results consolidate disjoint observations in a vast literature on pairwise correlations and point towards regularities of population coding in sensory cortex. PMID:26019310

  6. Miscellaneous uses of anabolic steroids.

    PubMed

    Kopera, H

    1993-01-01

    The original list of indications for anabolic-androgenic steroids has been reduced to those discussed in this publication so far and to mammary carcinoma, deficiency states and growth disorders. In disseminated endocrine-responsive mammary carcinoma in the female, anabolic drugs have a proven palliative effect in some 20 to 40% of patients, arresting tumour growth for up to 12 months and improving the patient's general condition. In high doses they can cause a disturbing increase in libido. Patients with deficiency states can, irrespective of the cause, benefit from adjunctive anabolic steroid treatment, provided their food supply is adequate. Positive effects are exerted by the anabolic agents' protein anabolic and anticatabolic actions, by psychic stimulation of the patient and by enhancement of recovery. Current trials strongly indicate that oral anabolic drugs administered alone or in combination with growth hormone or thyroid preparations are of therapeutic value in growth disorders such as constitutional delay of growth and puberty, hypopituitary dwarfism, chronic renal diseases and in Turner's syndrome.

  7. Anabolic steroids and growth hormone.

    PubMed

    Haupt, H A

    1993-01-01

    Athletes are generally well educated regarding substances that they may use as ergogenic aids. This includes anabolic steroids and growth hormone. Fortunately, the abuse of growth hormone is limited by its cost and the fact that anabolic steroids are simply more enticing to the athlete. There are, however, significant potential adverse effects regarding its use that can be best understood by studying known growth hormone excess, as demonstrated in the acromegalic syndrome. Many athletes are unfamiliar with this syndrome and education of the potential consequences of growth hormone excess is important in counseling athletes considering its use. While athletes contemplating the use of anabolic steroids may correctly perceive their risks for significant physiologic effects to be small if they use the steroids for brief periods of time, many of these same athletes are unaware of the potential for habituation to the use of anabolic steroids. The result may be incessant use of steroids by an athlete who previously considered only short-term use. As we see athletes taking anabolic steroids for more prolonged periods, we are likely to see more severe medical consequences. Those who eventually do discontinue the steroids are dismayed to find that the improvements made with the steroids generally disappear and they have little to show for hours or even years of intense training beyond the psychological scars inherent with steroid use. Counseling of these athletes should focus on the potential adverse psychological consequences of anabolic steroid use and the significant risk for habituation.

  8. Identifying Key Hospital Service Quality Factors in Online Health Communities

    PubMed Central

    Jung, Yuchul; Hur, Cinyoung; Jung, Dain

    2015-01-01

    Background The volume of health-related user-created content, especially hospital-related questions and answers in online health communities, has rapidly increased. Patients and caregivers participate in online community activities to share their experiences, exchange information, and ask about recommended or discredited hospitals. However, there is little research on how to identify hospital service quality automatically from the online communities. In the past, in-depth analysis of hospitals has used random sampling surveys. However, such surveys are becoming impractical owing to the rapidly increasing volume of online data and the diverse analysis requirements of related stakeholders. Objective As a solution for utilizing large-scale health-related information, we propose a novel approach to identify hospital service quality factors and overtime trends automatically from online health communities, especially hospital-related questions and answers. Methods We defined social media–based key quality factors for hospitals. In addition, we developed text mining techniques to detect such factors that frequently occur in online health communities. After detecting these factors that represent qualitative aspects of hospitals, we applied a sentiment analysis to recognize the types of recommendations in messages posted within online health communities. Korea’s two biggest online portals were used to test the effectiveness of detection of social media–based key quality factors for hospitals. Results To evaluate the proposed text mining techniques, we performed manual evaluations on the extraction and classification results, such as hospital name, service quality factors, and recommendation types using a random sample of messages (ie, 5.44% (9450/173,748) of the total messages). Service quality factor detection and hospital name extraction achieved average F1 scores of 91% and 78%, respectively. In terms of recommendation classification, performance (ie, precision) is

  9. Anabolic steroids abuse and male infertility.

    PubMed

    El Osta, Rabih; Almont, Thierry; Diligent, Catherine; Hubert, Nicolas; Eschwège, Pascal; Hubert, Jacques

    2016-01-01

    For several decades, testosterone and its synthetic derivatives have been used with anabolic and androgenic purposes. These substances were first restricted to professional bodybuilders, but become more and more popular among recreational athletes. Up to date, 3,000,000 anabolic-androgenic steroids (AAS) users have been reported in the United States with an increasing prevalence, making AAS consumption a major public health growing concern. Infertility is defined by the WHO as the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse and a male factor is present in up to 50 % of all infertile couples. Several conditions may be related to male infertility. Substance abuse, including AAS, is commonly associated to transient or persistent impairment on male reproductive function, through different pathways. Herein, a brief overview on AAS is offered. Steroids biochemistry, patterns of use, physiological and clinical issues are enlightened. A further review about fertility outcomes among male AAS abusers is also presented, including the classic reports on transient anabolic steroid-induced hypogonadism (ASIH), and the more recent experimental reports on structural and genetic sperm damage.

  10. Key factors of successful JIT integration with IBS - An overview

    NASA Astrophysics Data System (ADS)

    Asri, Mohammad Azwanie Naim Mohammad; Nawi, Mohd Nasrun Mohd; Nadarajan, Santhirasegaran

    2016-08-01

    The Just-In-Time (JIT) philosophy has been used for many decades to increase productivity through waste elimination process. The purpose of this paper is to contribute to the knowledge by addressing the transportation and material delivery activities in Industrialized Building System (IBS) and integrating JIT to improve the performance of those activities. The literature review has been conducted through relevant database. It was found that there is a need for more holistic approach to be adopted to integrate JIT in IBS project. This paper discusses the key success factors for effective integration between JIT and IBS in the context of transportation and material delivery activities.

  11. On the Free Energy That Drove Primordial Anabolism

    PubMed Central

    Kaufmann, Michael

    2009-01-01

    A key problem in understanding the origin of life is to explain the mechanism(s) that led to the spontaneous assembly of molecular building blocks that ultimately resulted in the appearance of macromolecular structures as they are known in modern biochemistry today. An indispensable thermodynamic prerequisite for such a primordial anabolism is the mechanistic coupling to processes that supplied the free energy required. Here I review different sources of free energy and discuss the potential of each form having been involved in the very first anabolic reactions that were fundamental to increase molecular complexity and thus were essential for life. PMID:19468343

  12. Emerging anabolic treatments in osteoporosis.

    PubMed

    Mosekilde, Leif; Tørring, Ove; Rejnmark, Lars

    2011-04-01

    Anabolic treatment that remodels bone tissue and restores bone biomechanical competence is essential in the treatment of osteoporosis. In addition, long term antiresorptive therapy may have limitations because of the reduced renewal of bone tissue. The only pure anabolic drugs available at present are intact PTH (1-84) (Preotact®) and the truncated PTH (1-34) (Teriparatide, Forteo®) while strontium ranelate may possess antiresorptive as well as anabolic properties. The marketed antiresorptive and anabolic antiosteoporotic drugs have limitations in their use due to adverse effects or to the occurrence of rare but severe late complications. Furthermore, indications may be restricted by co-existing diseases or treatment duration may be limited. However, new anabolic drugs are being developed mimicking the effect of PTH, or targeting the calcium sensing receptor (CaSR) or the Wnt/β-catenin signalling pathway. The PTH mimetics are truncated or altered PTH fragments, parathyroid hormone related peptide (PTHrP) and calcilytics stimulating endogenous PTH secretion. Calcimimetics (e.g. strontium) and calcilytics (e.g. lithium) may also affect bone cells directly through the CaSR. The Wnt pathway that stimulates osteoblastic proliferation, differentiation and function may be activated by neutralizing antibodies to secreted inhibitors of Wnt signalling (e.g. Sclerostin or Dickkopf) or by small molecules (e.g. lithium) that inhibits the glycogen synthase kinase 3β mediated degradation of β-catenin. Finally, blocking of activin A by soluble receptor fusion proteins has been shown to increase bone mass by a dual anabolic-antiresorptive action. The present paper summarises the physiological background and the present evidence for these effects.

  13. Anabolic steroids and cardiovascular risk.

    PubMed

    Angell, Peter; Chester, Neil; Green, Danny; Somauroo, John; Whyte, Greg; George, Keith

    2012-02-01

    Recent reports from needle exchange programmes and other public health initiatives have suggested growing use of anabolic steroids (AS) in the UK and other countries. Data indicate that AS use is not confined to body-builders or high-level sportsmen. Use has spread to professionals working in emergency services, casual fitness enthusiasts and subelite sportsmen and women. Although the precise health consequences of AS use is largely undefined, AS use represents a growing public health concern. Data regarding the consequences of AS use on cardiovascular health are limited to case studies and a modest number of small cohort studies. Numerous case studies have linked AS use with a variety of cardiovascular disease (CVD) events or endpoints, including myocardial infarction, stroke and death. Large-scale epidemiological studies to support these links are absent. Consequently, the impact of AS use upon known CVD risk factors has been studied in relatively small, case-series studies. Data relating AS use to elevated blood pressure, altered lipid profiles and ECG abnormalities have been reported, but are often limited in scope, and other studies have often produced equivocal outcomes. The use of AS has been linked to the appearance of concentric left ventricular hypertrophy as well as endothelial dysfunction but the data again remains controversial. The mechanisms responsible for the negative effect of AS on cardiovascular health are poorly understood, especially in humans. Possibilities include direct effects on myocytes and endothelial cells, reduced intracellular Ca2+ levels, increased release of apoptogenic factors, as well as increased collagen crosslinks between myocytes. New data relating AS use to cardiovascular health risks are emerging, as novel technologies are developed (especially in non-invasive imaging) that can assess physiological structure and function. Continued efforts to fully document the cardiovascular health consequences of AS use is important to

  14. Anabolic Steroid Reversal of Denervation Atrophy

    DTIC Science & Technology

    2012-03-01

    10-1-0932 TITLE: Anabolic Steroid Reversal of Denervation Atrophy PRINCIPAL INVESTIGATOR: Dr. Jonathan E. Isaacs...certainly “denervation atrophy” plays a significant role. Anabolic steroids , which have been shown to cause hypertrophy of muscle fibers, increase net...of satellite cells to muscle fibers. In conclusion, there did not seem to be a functional benefit for anabolic steroid treatment following

  15. Key factors affecting mechanical behavior of metallic glass nanowires

    PubMed Central

    Zhang, Qi; Li, Qi-Kai; Li, Mo

    2017-01-01

    Both strengthening and weakening trends with decreasing diameter have been observed for metallic glass nanowires, sometimes even in the samples with the same chemical composition. How to reconcile the results has reminded a puzzle. Since the detailed stress state and microstructure of metallic glass nanowires may differ from each other significantly depending on preparation, to discover the intrinsic size effect it is necessary to study metallic glass nanowires fabricated differently. Here we show the complex size effects from one such class of metallic glass nanowires prepared by casting using molecular dynamics simulations. As compared with the nanowires of the same composition prepared by other methods, the cast nanowires deform nearly homogeneously with much lower strength but better ductility; and also show strengthening in tension but weakening in compression with decreasing wire diameter. The subtle size dependence is shown to be related to the key factors including internal and surface stress state, atomic structure variation, and presence of various gradients. The complex interplay of these factors at decreasing size leads to the different deformation behaviors. PMID:28134292

  16. Key factors affecting mechanical behavior of metallic glass nanowires

    NASA Astrophysics Data System (ADS)

    Zhang, Qi; Li, Qi-Kai; Li, Mo

    2017-01-01

    Both strengthening and weakening trends with decreasing diameter have been observed for metallic glass nanowires, sometimes even in the samples with the same chemical composition. How to reconcile the results has reminded a puzzle. Since the detailed stress state and microstructure of metallic glass nanowires may differ from each other significantly depending on preparation, to discover the intrinsic size effect it is necessary to study metallic glass nanowires fabricated differently. Here we show the complex size effects from one such class of metallic glass nanowires prepared by casting using molecular dynamics simulations. As compared with the nanowires of the same composition prepared by other methods, the cast nanowires deform nearly homogeneously with much lower strength but better ductility; and also show strengthening in tension but weakening in compression with decreasing wire diameter. The subtle size dependence is shown to be related to the key factors including internal and surface stress state, atomic structure variation, and presence of various gradients. The complex interplay of these factors at decreasing size leads to the different deformation behaviors.

  17. Key Response Planning Factors for the Aftermath of Nuclear Terrorism

    SciTech Connect

    Buddemeier, B R; Dillon, M B

    2009-01-21

    Despite hundreds of above-ground nuclear tests and data gathered from Hiroshima and Nagasaki, the effects of a ground-level, low-yield nuclear detonation in a modern urban environment are still the subject of considerable scientific debate. Extensive review of nuclear weapon effects studies and discussions with nuclear weapon effects experts from various federal agencies, national laboratories, and technical organizations have identified key issues and bounded some of the unknowns required to support response planning for a low-yield, ground-level nuclear detonation in a modern U.S. city. This study, which is focused primarily upon the hazards posed by radioactive fallout, used detailed fallout predictions from the advanced suite of three-dimensional (3-D) meteorology and plume/fallout models developed at Lawrence Livermore National Laboratory (LLNL), including extensive global Key Response Planning Factors for the Aftermath of Nuclear Terrorism geographical and real-time meteorological databases to support model calculations. This 3-D modeling system provides detailed simulations that account for complex meteorology and terrain effects. The results of initial modeling and analysis were presented to federal, state, and local working groups to obtain critical, broad-based review and feedback on strategy and messaging. This effort involved a diverse set of communities, including New York City, National Capitol Regions, Charlotte, Houston, Portland, and Los Angeles. The largest potential for reducing casualties during the post-detonation response phase comes from reducing exposure to fallout radiation. This can be accomplished through early, adequate sheltering followed by informed, delayed evacuation.B The response challenges to a nuclear detonation must be solved through multiple approaches of public education, planning, and rapid response actions. Because the successful response will require extensive coordination of a large number of organizations, supplemented by

  18. Manifestation of severe coronary heart disease after anabolic drug abuse.

    PubMed

    Mewis, C; Spyridopoulos, I; Kühlkamp, V; Seipel, L

    1996-02-01

    Anabolic steroids are frequently abused, thus increasing the risk of cardiovascular disease, despite the known unfavorable influence on lipid profiles. We report on a young bodybuilder who presented with ventricular tachycardia as the first manifestation of severe underlying coronary heart disease. Coronary angiogram revealed severe stenotic lesions in the right coronary artery and the left descending coronary artery, and hypokinetic regions corresponded to posterolateral and anterior myocardial infarctions. This young patient had a history without any coronary risk factors, but with a 2-year abuse of the anabolic steroid stanazolol. No report published so far has shown possible atherogenic consequences of long-term abuse of stanazolol.

  19. [Myocardial infarction and anabolic steroid use. A case report].

    PubMed

    Godon, P; Bonnefoy, E; Guérard, S; Munet, M; Velon, S; Brion, R; Touboul, P

    2000-07-01

    The potential cardiotoxicity of anabolic steroids is not well known. The authors report the case of a young man who was a top class body builder and who developed severe ischaemic cardiomyopathy presenting with an inferior wall myocardial infarction. The clinical history revealed prolonged and intensive usage of two types of anabolic steroids to be the only risk factor. This cardiotoxicity may be related to several physiopathological mechanisms: accelerated atherogenesis by lipid changes, increased platelet aggregation, coronary spasm or a direct toxic effect on the myocytes. The apparent scarcity of the reported clinical details in the literature is probably an underestimation of the consequences of this usage.

  20. Endocrine aspects of anabolic steroids.

    PubMed

    Wu, F C

    1997-07-01

    Understanding of the mechanism of androgen action has been enhanced by advances in knowledge on the molecular basis of activation of the androgen receptor and the importance of tissue conversion of circulating testosterone to dihydrotestosterone and estradiol. New evidence supports the view that supraphysiological doses of anabolic steroids do have a definite, positive effect on muscle size and muscle strength. However, the nature of the anabolic action of androgens on muscle is currently unclear and may involve mechanisms independent of the androgen receptor. The dose-response relationships of anabolic actions vs the potentially serious risk to health of androgenic-anabolic steroids (AAS) use are still unresolved. Most of the adverse effects of AAS are reversible but some are permanent, particularly in women and children. The reported incidence of acute life-threatening events associated with AAS abuse is low, but the actual risk may be underrecognized or underreported; the exact incidence is unknown. The long-term consequences and disease risks of AAS to the sports competitor remain to be properly evaluated.

  1. Anabolic androgenic steroids abuse and liver toxicity.

    PubMed

    Neri, M; Bello, S; Bonsignore, A; Cantatore, S; Riezzo, I; Turillazzi, E; Fineschi, V

    2011-05-01

    In the athletes the wide use of Anabolic Androgenic Steroids (AAS) cause series damage in various organs, in particular, analyzing the liver, elevation on the levels of liver enzymes, cholestatic jaundice, liver tumors, both benign and malignant, and peliosis hepatis are described. A prolonged AAS administration provokes an increase in the activities of liver lysosomal hydrolases and a decrease in some components of the microsomal drug-metabolizing system and in the activity of the mitochondrial respiratory chain complexes without modifying classical serum indicators of hepatic function. Liver is a key organ actively involved in numerous metabolic and detoxifying functions. As a consequence, it is continuously exposed to high levels of endogenous and exogenous oxidants that are by-products of many biochemical pathways and, in fact, it has been demonstrated that intracellular oxidant production is more active in liver than in tissues, like the increase of inflammatory cytokines, apoptosis and the inhibitors of apoptosis NF- κB and Heat Shock Proteins.

  2. Atrial fibrillation and anabolic steroids.

    PubMed

    Sullivan, M L; Martinez, C M; Gallagher, E J

    1999-01-01

    A young male bodybuilder, consuming large doses of anabolic steroids (AS), presented to the Emergency Department (ED) with symptomatic rapid atrial fibrillation (AF). Echocardiogram revealed significant septal hypokinesis, and posterior and septal wall thickness at the upper limit of normal for highly trained athletes. The atrial fibrillation had not recurred at 10 weeks after discontinuation of AS use. Consumption of these agents in athletes has been associated with hypertension, ischemic heart disease, hypertrophic cardiomyopathy, and sudden death.

  3. The incidence of anabolic steroid use among competitive bodybuilders.

    PubMed

    Tricker, R; O'Neill, M R; Cook, D

    1989-01-01

    The purpose of this study was to determine the incidence of anabolic steroid use among competitive male and female bodybuilders in Kansas and Missouri. A profile was established for users and non-users of anabolic steroids. The results of this study indicated that more than half of the male bodybuilders (54%) were using steroids on a regular basis compared to 10 percent of the female competitors. The types of steroid used were investigated and revealed that on average, four different types of anabolic steroid were used during the year, with individual use ranging from one to fifteen different types; including Dianabol, Deca Durabolin, Anavar, Testosterone, Androl 50, Winstrol, Primobolan, Equipoise, Finaject, Parabolin, HCG, Primacetate, Enanthate, Halotestin, and Maxibolin, in order of the most to least frequently used. The female bodybuilders reported that they had used an average of two different steroids including Deca Durabolin, Anavar, Testosterone, Dianabol, Equipoise, and Winstrol. The principal reason bodybuilders used steroids was related to their perception that these drugs were an important factor in winning competitions. Another important motivating factor for use was consistent with reports that significant gains in strength could be achieved by including anabolic steroids as part of the training regimen in spite of the reported adverse side-effects.

  4. Anabolic steroids are fool's gold.

    PubMed

    Ryan, A J

    1981-10-01

    Since increases in muscle strength are proportional to increases in the cross-sectional diameter of the muscles being trained, the body must convert greater than normal amounts of amino acids available to it to increase size in athletes in training. When androgens became available in the 1930's they were used primarily to restore positive nitrogen balance in victims of starvation. Anabolic steroids, which were developed to avoid unwanted effects of androgens, were first given to weight lifters, but football players and weight throwers were soon using them. From 1965 to 1977, 25 clinical studies were published dealing with the administration of an anabolic-androgenic steroid to adult human males for evaluating changes in strength and, in 10 of these studies, in maximum oxygen consumption. In 12 of these studies, improvements were claimed from the use of these steroids; in the other 13 no improvements were observed. Other studies have shown that in healthy adult males these steroids reduce testosterone and gonadotrophin output, which reduces spermatogenesis. Alterations of normal liver function have been found in up to 80% of persons treated with C17-alkylated testosterone derivatives. Peliosis hepatitis, with liver failure and death, and fatal liver cancer have also been reported in adults so treated. Reliable methods for detecting anabolic steroids in the urine are now used in certain international competitions. Testing, announced bans, and disqualifications have not been effective in controlling the use of the drugs. The best hope for doing so lies in continuing education of athletes and their supervisors.

  5. Anabolic steroids: a review of the literature.

    PubMed

    Haupt, H A; Rovere, G D

    1984-01-01

    The use of anabolic steroids by athletes is controversial. On the one hand, many athletes believe that steroids improve athletic performance and thus provide an advantage to those who use them. On the other hand, the medical and scientific communities believe that inadequate scientific data exist to support the claim that anabolic steroids can improve athletic performance while overwhelming scientific data demonstrate their deleterious effects. Therefore, a large information and credibility gap concerning anabolic steroids exists between the athletes and the medical and scientific communities. We believe that this gap can be closed if both groups are better informed about anabolic steroids. We provide a detailed review of the literature on anabolic steroids that provides to the reader the information needed to make an informed decision on the relative risks and benefits of anabolic steroids to the athlete.

  6. Tendencies and Key Factors in the Health of School Students

    ERIC Educational Resources Information Center

    Rimashevskaia, N. M.; Shabunova, A. A.

    2013-01-01

    According to research data, in today's Russia 70 percent of children are born with various health risk factors, and this leads to a rapid deterioration of their health during their school years. The health of school students is getting worse as a consequence of the effect of a whole set of social and economic and psychological factors, and the…

  7. Succesful Lean Manufacturing Implementation: Internal Key Influencing Factors

    NASA Astrophysics Data System (ADS)

    Virginia, Iuga; Claudiu, Kifor

    2015-09-01

    Manufacturing sectors and companies all over the world are successfully implementing lean principles within their processes. Nowadays, lean has become an indispensable part of global players. Companies worldwide need to be aware of multiple factors which weigh heavily on the success or failure of lean implementation. This paper focuses on giving a brief and structured overview over the fundamental organizational factors which play a substantial role for the lean manufacturing (LM) implementation process. The study below focuses on internal factors which are indispensable for a successful LM implementation within organizations. It is imperative that these internal factors are known, recognized and taken into consideration during the whole LM implementation process. Ignoring their influence on the process's implementation may lead to endangering the expected results or to making the process more difficult which could result in much higher human resource consumption.

  8. Anabolic androgenic steroid-induced hepatotoxicity.

    PubMed

    Bond, Peter; Llewellyn, William; Van Mol, Peter

    2016-08-01

    Anabolic androgenic steroids (AAS) have been abused for decades by both professional and amateur athletes in order to improve physical performance or muscle mass. AAS abuse can cause adverse effects, among which are hepatotoxic effects. These effects include cholestatic icterus and possibly peliosis hepatis and hepatocellular carcinoma or adenoma. In particular, 17α-alkylated AAS appear to be hepatotoxic, whereas nonalkylated AAS appear not to be. The 17α-alkyl substitution retards hepatic metabolism of the AAS rendering it orally bioavailable. The mechanism responsible for the hepatotoxicity induced by 17α-alkylated AAS remains poorly understood. However, oxidative stress has been repeatedly shown to be associated with it. In this manuscript we present a hypothesis which describes a potential mechanism responsible for AAS-induced hepatotoxicity, based on several observations from the literature which suggest oxidative stress being a causal factor.

  9. Ethylene, a key factor in the regulation of seed dormancy

    PubMed Central

    Corbineau, Françoise; Xia, Qiong; Bailly, Christophe

    2014-01-01

    Ethylene is an important component of the gaseous environment, and regulates numerous plant developmental processes including seed germination and seedling establishment. Dormancy, the inability to germinate in apparently favorable conditions, has been demonstrated to be regulated by the hormonal balance between abscisic acid (ABA) and gibberellins (GAs). Ethylene plays a key role in dormancy release in numerous species, the effective concentrations allowing the germination of dormant seeds ranging between 0.1 and 200 μL L-1. Studies using inhibitors of ethylene biosynthesis or of ethylene action and analysis of mutant lines altered in genes involved in the ethylene signaling pathway (etr1, ein2, ain1, etr1, and erf1) demonstrate the involvement of ethylene in the regulation of germination and dormancy. Ethylene counteracts ABA effects through a regulation of ABA metabolism and signaling pathways. Moreover, ethylene insensitive mutants in Arabidopsis are more sensitive to ABA and the seeds are more dormant. Numerous data also show an interaction between ABA, GAs and ethylene metabolism and signaling pathways. It has been increasingly demonstrated that reactive oxygen species (ROS) may play a significant role in the regulation of seed germination interacting with hormonal signaling pathways. In the present review the responsiveness of seeds to ethylene will be described, and the key role of ethylene in the regulation of seed dormancy via a crosstalk between hormones and other signals will be discussed. PMID:25346747

  10. The Human Factor: A Key to Excellence in Education.

    ERIC Educational Resources Information Center

    Mintzies, Paula; Hare, Isadora

    This document contends that efforts designed to determine how schools can educate children for the nation of tomorrow, by focusing primarily on curriculum issues, instruction, and teachers, may have overlooked the interpersonal factors which contribute to excellence and those human and social forces which may interfere with the attainment of…

  11. Leadership and management quality: key factors in effective health systems.

    PubMed

    Pfeffermann, Guy

    2012-01-01

    The effectiveness of health care systems in the developing world is related to the quality of their leadership and management, yet that factor has been neglected by academics and funders. Based on replicable existing models, the article proposes an approach to strengthening local management training institutions.

  12. Key success factors behind electronic medical record adoption in Thailand.

    PubMed

    Narattharaksa, Kanida; Speece, Mark; Newton, Charles; Bulyalert, Damrongsak

    2016-09-19

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

  13. Hypoxia-inducible factors as key regulators of tumor inflammation.

    PubMed

    Mamlouk, Soulafa; Wielockx, Ben

    2013-06-15

    Low levels of oxygen or hypoxia is often an obstacle in health, particularly in pathological disorders like cancer. The main family of transcription factors responsible for cell survival and adaptation under strenuous conditions of hypoxia are the "hypoxia-inducible factors" (HIFs). Together with prolyl hydroxylase domain enzymes (PHDs), HIFs regulates tumor angiogenesis, proliferation, invasion, metastasis, in addition to resistance to radiation and chemotherapy. Additionally, the entire HIF transcription cascade is involved in the "seventh" hallmark of cancer; inflammation. Studies have shown that hypoxia can influence tumor associated immune cells toward assisting in tumor proliferation, differentiation, vessel growth, distant metastasis and suppression of the immune response via cytokine expression alterations. These changes are not necessarily analogous to HIF's role in non-cancer immune responses, where hypoxia often encourages a strong inflammatory response.

  14. Detection of key factors affecting lycopene in vitro accessibility.

    PubMed

    Periago, M J; Bravo, S; García-Alonso, F J; Rincón, F

    2013-04-24

    On the basis of a Plackett-Burman experimental design for a resolution IV level obtained via a foldover strategy, the effect of 11 factors on lycopene in vitro accessibility was investigated. The selected factors were thermal treatment (X1), olive oil addition (X2), gastric pH (X3), gastric digestion time (X4), pepsin concentration (X5), intestinal pH (X6), pancreatin concentration (X7), bile salts concentration (X8), colipase addition (X9), intestinal digestion time (X10), and intestinal digestion speed (X11). Tomato passata was used as a natural source of lycopene. Samples were collected after gastric and intestinal digestion, and from the micellar phase, to quantify the (all-E)-lycopene and its (Z)-isomers by HPLC. Except for X3, X6, X7, and X11, the other factors studied explained lycopene in vitro accessibility, mainly regarding intestinal digestion, with R(2) values ≥ 0.60. Our results showed that the accessibility of lycopene is influenced by the conditions applied during in vitro intestinal digestion.

  15. Fibroblast growth factor 21 - a key player in cardiovascular disorders?

    PubMed

    Lenart-Lipińska, Monika; Duma, Dariusz; Hałabiś, Magdalena; Dziedzic, Marcin; Solski, Janusz

    2016-06-15

    Fibroblast growth factor 21 (FGF21) is a newly discovered adipokine, synthesized by several organs, mostly by the liver, which was introduced as a potent metabolic regulator and insulin-sensitizing factor. Numerous animal studies have demonstrated that FGF21 improves glucose and lipids metabolism and exerts anti-inflammatory effects. However, data obtained from human studies have shown contradictory results, in which circulating FGF21 levels were often elevated in obesity, dyslipidemia, type 2 diabetes (DM2) and other conditions connected with insulin resistance. This increase in basal FGF21 concentrations observed in patients with obesity and other conditions related to insulin resistance was being explained as a compensatory response to the underlying metabolic disturbances or tissue resistance to FGF21 action. Furthermore, the results of clinical trials have shown that increased FGF21 concentrations were associated with increased cardiovascular (CV) risk and had a prognostic value in CV outcomes. In recent years, it has been reported that FGF21 may exert cardioprotective effects. This mini-review aims to summarize the current state of knowledge about the role of FGF21 in CV disorders, and discuss the molecular mechanism underlying the anti-atherogenic properties of this compound.

  16. Key biogeochemical factors affecting soil carbon storage in Posidonia meadows

    NASA Astrophysics Data System (ADS)

    Serrano, Oscar; Ricart, Aurora M.; Lavery, Paul S.; Mateo, Miguel Angel; Arias-Ortiz, Ariane; Masque, Pere; Rozaimi, Mohammad; Steven, Andy; Duarte, Carlos M.

    2016-08-01

    Biotic and abiotic factors influence the accumulation of organic carbon (Corg) in seagrass ecosystems. We surveyed Posidonia sinuosa meadows growing in different water depths to assess the variability in the sources, stocks and accumulation rates of Corg. We show that over the last 500 years, P. sinuosa meadows closer to the upper limit of distribution (at 2-4 m depth) accumulated 3- to 4-fold higher Corg stocks (averaging 6.3 kg Corg m-2) at 3- to 4-fold higher rates (12.8 g Corg m-2 yr-1) compared to meadows closer to the deep limits of distribution (at 6-8 m depth; 1.8 kg Corg m-2 and 3.6 g Corg m-2 yr-1). In shallower meadows, Corg stocks were mostly derived from seagrass detritus (88 % in average) compared to meadows closer to the deep limit of distribution (45 % on average). In addition, soil accumulation rates and fine-grained sediment content (< 0.125 mm) in shallower meadows (2.0 mm yr-1 and 9 %, respectively) were approximately 2-fold higher than in deeper meadows (1.2 mm yr-1 and 5 %, respectively). The Corg stocks and accumulation rates accumulated over the last 500 years in bare sediments (0.6 kg Corg m-2 and 1.2 g Corg m-2 yr-1) were 3- to 11-fold lower than in P. sinuosa meadows, while fine-grained sediment content (1 %) and seagrass detritus contribution to the Corg pool (20 %) were 8- and 3-fold lower than in Posidonia meadows, respectively. The patterns found support the hypothesis that Corg storage in seagrass soils is influenced by interactions of biological (e.g., meadow productivity, cover and density), chemical (e.g., recalcitrance of Corg stocks) and physical (e.g., hydrodynamic energy and soil accumulation rates) factors within the meadow. We conclude that there is a need to improve global estimates of seagrass carbon storage accounting for biogeochemical factors driving variability within habitats.

  17. Etiology of obesity: two "key issues" and other emerging factors.

    PubMed

    Serra-Majem, Lluis; Bautista-Castaño, Inmaculada

    2013-09-01

    The current obesity epidemic is known to have coincided with profound societal changes involving both physical activity levels and food consumption patterns as well as demographic and cultural changes affecting the conduct of human beings in various ways. On the other hand, obesity is a complex and multifactorial chronic disease that usually becomes manifest in child hood and adolescence. Its origin is a genetic and environmental interchange, of which environmental or behavioral factors play the most important role, stemming from an imbalance between energy intake and expenditure. Still and all, it is rather simplistic to assume that obesity is only due to excessive consumption and/or deficient physical activity levels. Currently, various lines of investigation have been initiated that evaluate the determinants of obesity, of which nutrigenomics and gut microbiota deserve special attention.

  18. Circulation a key factor in Mediterranean algal growth

    NASA Astrophysics Data System (ADS)

    Orwig, Jessica

    2014-12-01

    The early appearance of nitrate in December appears to have been the driving force for favorable conditions for algal blooms in the Mediterranean, a new study indicates. To better understand the role of nutrients' availability to enable the growth of phytoplankton in temperate seas, D'Ortenzio et al. installed nitrate concentration sensors on two profiling floats in the northwestern Mediterranean basin in summer 2011. Each spring, the phytoplankton in this basin rapidly grow to form a bloom that blankets the surface and contributes to the transport of carbon from the atmosphere to the deep ocean. Scientists are still unsure exactly what produces the conditions for these blooms, but they know that the availability of nutrients, induced by large-scale circulation in the oceans, during the winter is a factor.

  19. Key factors affecting urban runoff pollution under cold climatic conditions

    NASA Astrophysics Data System (ADS)

    Valtanen, Marjo; Sillanpää, Nora; Setälä, Heikki

    2015-10-01

    Urban runoff contains various pollutants and has the potential of deteriorating the quality of aquatic ecosystems. In this study our objective is to shed light on the factors that control the runoff water quality in urbanized catchments. The effects of runoff event characteristics, land use type and catchment imperviousness on event mass loads (EML) and event mean concentrations (EMC) were studied during warm and cold periods in three study catchments (6.1, 6.5 and 12.6 ha in size) in the city of Lahti, Finland. Runoff and rainfall were measured continuously for two years at each catchment. Runoff samples were taken for total nutrients (tot-P and tot-N), total suspended solids (TSS), heavy metals (Zn, Cr, Al, Co, Ni, Cu, Pb, Mn) and total organic carbon (TOC). Stepwise multiple linear regression analysis (SMLR) was used to identify general relationships between the following variables: event water quality, runoff event characteristics and catchment characteristics. In general, the studied variables explained 50-90% of the EMLs but only 30-60% of the EMCs, with runoff duration having an important role in most of the SMLR models. Mean runoff intensity or peak flow was also often included in the runoff quality models. Yet, the importance (being the first, second or third best) and role (negative or positive impact) of the explanatory variables varied between the cold and warm period. Land use type often explained cold period concentrations, but imperviousness alone explained EMCs weakly. As for EMLs, the influence of imperviousness and/or land use was season and pollutant dependent. The study suggests that pollutant loads can be - throughout the year - adequately predicted by runoff characteristics given that seasonal differences are taken into account. Although pollutant concentrations were sensitive to variation in seasonal and catchment conditions as well, the accurate estimation of EMCs would require a more complete set of explanatory factors than used in this

  20. Risk factor control is key in diabetic nephropathy.

    PubMed

    Lewis, Gareth; Maxwell, Alexander P

    2014-02-01

    Prolonged duration of diabetes, poor glycaemic control and hypertension are major risk factors for both diabetic nephropathy and cardiovascular disease. Optimising blood sugar control together with excellent control of blood pressure can reduce the risk of developing diabetic nephropathy. Diabetic nephropathy should be considered in any patient with diabetes when persistent albuminuria develops. Microalbuminuria is the earliest clinically detectable indicator of diabetic nephropathy risk. The majority of patients with diabetic nephropathy are appropriately diagnosed based on elevated urinary albumin excretion and/or reduced 0032-6518 renal function. Patients with type 2 diabetes should have annual urinary ACR measurements from the time of diabetes diagnosis while those with type 1 diabetes should commence five years after diagnosis. Blood pressure lowering to 130/80mmHg and reduction of proteinuria to <1 g/day retards progression of diabetic nephropathy and reduces the number of cardiovascular events. Drugs that block the renin-angiotensin-aldosterone system (RAAS) are effective in reducing proteinuria, managing hypertension and reducing cardiovascular risk. Unless there are clear contraindications or intolerance all patients with diabetic nephropathy should be prescribed an ACEI or ARB. Stopping an ACEI or ARB during intercurrent illness or times of volume depletion is critically important. Patients with diabetic nephropathy should have at least yearly measurements of blood pressure, renal function and urinary ACR.

  1. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  2. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  3. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  4. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  5. 21 CFR 1308.34 - Exempt anabolic steroid products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Exempt anabolic steroid products. 1308.34 Section... SUBSTANCES Exempt Anabolic Steroid Products § 1308.34 Exempt anabolic steroid products. The list of compounds, mixtures, or preparations that contain an anabolic steroid that have been exempted by the...

  6. The Future of Government Funding for Persons with Disabilities: Some Key Factors.

    ERIC Educational Resources Information Center

    Ross, E. Clarke

    1980-01-01

    The paper identifies and discusses key factors associated with government funding for disabled individuals. An introductory section traces the growth of public expenditures in recent years. Five key factors affecting government funding are examined (sample subtopics in parentheses): state government tax and spending limits (Proposition 13 and the…

  7. Anabolic steroid abuse and dependence.

    PubMed

    Brower, Kirk J

    2002-10-01

    Anabolic-androgenic steroids (AAS) are mainly used to treat androgen deficiency syndromes and, more recently, catabolic states such as AIDS-associated wasting. There is no evidence in the reviewed literature that AAS abuse or dependence develops from the therapeutic use of AAS. Conversely, 165 instances of AAS dependence have been reported among weightlifters and bodybuilders who, as part of their weight training regimens, chronically administered supraphysiologic doses, often including combinations of injected and oral AAS as well as other drugs of abuse. A new model is proposed in which both the "myoactive" and psychoactive effects of AAS contribute to the development of AAS dependence. The adverse consequences of AAS are reviewed, as well as their assessment by means of a history and physical, mental status examination, and laboratory testing. When patients with AAS use disorders are compared with patients with other substance use disorders, both similarities and differences become apparent and have implications for treatment.

  8. Anabolic effect of plant brassinosteroid

    PubMed Central

    Esposito, Debora; Komarnytsky, Slavko; Shapses, Sue; Raskin, Ilya

    2011-01-01

    Brassinosteroids are plant-derived polyhydroxylated derivatives of 5a-cholestane, structurally similar to cholesterol-derived animal steroid hormones and insect ecdysteroids, with no known function in mammals. 28-Homobrassinolide (HB), a steroidal lactone with potent plant growth-promoting property, stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells (EC50 4 μM) mediated in part by PI3K/Akt signaling pathway. Oral administration of HB (20 or 60 mg/kg/d for 24 d) to healthy rats fed normal diet (protein content 23.9%) increased food intake, body weight gain, lean body mass, and gastrocnemius muscle mass as compared with vehicle-treated controls. The effect of HB administration increased slightly in animals fed a high-protein diet (protein content 39.4%). Both oral (up to 60 mg/kg) and subcutaneous (up to 4 mg/kg) administration of HB showed low androgenic activity when tested in the Hershberger assay. Moreover, HB showed no direct binding to the androgen receptor in vitro. HB treatment was also associated with an improved physical fitness of untrained healthy rats, as evident from a 6.7% increase in lower extremity strength, measured by grip test. In the gastrocnemius muscle of castrated animals, HB treatment significantly increased the number of type IIa and IIb fibers and the cross-sectional area of type I and type IIa fibers. These findings suggest that oral application of HB triggers selective anabolic response with minimal or no androgenic side-effects and begin to elucidate the putative cellular targets for plant brassinosteroids in mammals.—Esposito, D., Komarnytsky, S., Shapses, S., Raskin, I. Anabolic effect of plant brassinosteroid. PMID:21746867

  9. Anabolic treatment with GH, IGF-I, or anabolic steroids in patients with HIV-associated wasting.

    PubMed

    Mulligan, Kathleen; Schambelan, Morris

    2002-09-01

    Wasting, and particularly loss of metabolically active lean tissue, contributes to increased mortality, accelerated disease progression, and impairment of strength and functional status in patients with HIV infection. A variety of protein anabolic agents, including growth hormone, insulin-like growth factor-I, testosterone, nandrolone decanoate, oxandrolone, and oxymetholone, have been studied in patients with HIV-associated wasting. Overall, these studies have demonstrated that treatment with protein anabolic agents can increase lean body mass (LBM) and in some cases provide functional benefits and improvements in quality of life. Further research is needed to determine whether such treatment prolongs survival or reduces the overall health care burden of HIV infection. The advances in identification of successful treatments for HIV-associated wasting can provide a model for using these therapies in other catabolic states, including end-stage renal disease, cancer, chronic obstructive pulmonary disease, and cardiac cachexia.

  10. Detecting the administration of endogenous anabolic androgenic steroids.

    PubMed

    Ayotte, Christiane

    2010-01-01

    The detection of the administration of an androgen such as testosterone that could be present normally in human bodily fluids is based upon the methodical evaluation of key parameters of the urinary profile of steroids, precisely measured by GC/MS. Over the years, the markers of utilization were identified, the reference ranges of diagnostic metabolites and ratios were established in volunteers and in populations of athletes, and their stability in individual subjects was studied. The direct confirmation comes from the measurement of delta (13)C values reflecting their synthetic origin, ruling out a potential physiological anomaly. Several factors may alter the individual GC/MS steroid profile besides the administration of a testosterone-related steroid, the nonexhaustive list ranging from the microbial degradation of the specimen, the utilization of inhibitors of 5alpha-reductase or other anabolic steroids, masking agents such as probenecid, to inebriating alcohol drinking. The limitation of the testing strategy comes from the potentially elevated rate of false negatives, since only the values exceeding those of the reference populations are picked up by the GC/MS screening analyses performed by the laboratories on blind samples, excluding individual particularities and subtle doping. Since the ranges of normal values are often described from samples collected in Western countries, extrapolating data to all athletes appears inefficient. Furthermore, with short half-life and topical formulations, the alterations of the steroid profile are less pronounced and disappear rapidly. GC/C/IRMS analyses are too delicate and fastidious to be considered for screening routine samples. An approach based upon the individual athlete's steroid profiling is necessary to pick up variations that would trigger further IRMS analysis and investigations.

  11. Enhanced Two-Factor Authentication and Key Agreement Using Dynamic Identities in Wireless Sensor Networks.

    PubMed

    Chang, I-Pin; Lee, Tian-Fu; Lin, Tsung-Hung; Liu, Chuan-Ming

    2015-11-30

    Key agreements that use only password authentication are convenient in communication networks, but these key agreement schemes often fail to resist possible attacks, and therefore provide poor security compared with some other authentication schemes. To increase security, many authentication and key agreement schemes use smartcard authentication in addition to passwords. Thus, two-factor authentication and key agreement schemes using smartcards and passwords are widely adopted in many applications. Vaidya et al. recently presented a two-factor authentication and key agreement scheme for wireless sensor networks (WSNs). Kim et al. observed that the Vaidya et al. scheme fails to resist gateway node bypassing and user impersonation attacks, and then proposed an improved scheme for WSNs. This study analyzes the weaknesses of the two-factor authentication and key agreement scheme of Kim et al., which include vulnerability to impersonation attacks, lost smartcard attacks and man-in-the-middle attacks, violation of session key security, and failure to protect user privacy. An efficient and secure authentication and key agreement scheme for WSNs based on the scheme of Kim et al. is then proposed. The proposed scheme not only solves the weaknesses of previous approaches, but also increases security requirements while maintaining low computational cost.

  12. Enhanced Two-Factor Authentication and Key Agreement Using Dynamic Identities in Wireless Sensor Networks

    PubMed Central

    Chang, I-Pin; Lee, Tian-Fu; Lin, Tsung-Hung; Liu, Chuan-Ming

    2015-01-01

    Key agreements that use only password authentication are convenient in communication networks, but these key agreement schemes often fail to resist possible attacks, and therefore provide poor security compared with some other authentication schemes. To increase security, many authentication and key agreement schemes use smartcard authentication in addition to passwords. Thus, two-factor authentication and key agreement schemes using smartcards and passwords are widely adopted in many applications. Vaidya et al. recently presented a two-factor authentication and key agreement scheme for wireless sensor networks (WSNs). Kim et al. observed that the Vaidya et al. scheme fails to resist gateway node bypassing and user impersonation attacks, and then proposed an improved scheme for WSNs. This study analyzes the weaknesses of the two-factor authentication and key agreement scheme of Kim et al., which include vulnerability to impersonation attacks, lost smartcard attacks and man-in-the-middle attacks, violation of session key security, and failure to protect user privacy. An efficient and secure authentication and key agreement scheme for WSNs based on the scheme of Kim et al. is then proposed. The proposed scheme not only solves the weaknesses of previous approaches, but also increases security requirements while maintaining low computational cost. PMID:26633396

  13. Teachers' Professional Development: What Are the Key Change Factors for Mathematics Teachers?

    ERIC Educational Resources Information Center

    Pehkonen, Erkki; Torner, Gunter

    1999-01-01

    Surveyed and interviewed 13 experienced German middle school mathematics teachers to examine key factors causing discontinuity in their professional development. Results included 49 statements about change that fell into four categories. Researchers extracted three change factors not reported in earlier literature: experiences and observations…

  14. Key factors, Soil N Processes, and nitrite accumulation affecting nitrous oxide emissions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A better understanding of the key factors affecting nitrous oxide (N2O) emission and potential mitigation strategies is essential for sustainable agriculture. The objective of this study was to examine the important factors affecting N2O emissions, soil processes involved, and potential mitigation s...

  15. Short Anabolic Peptides for Bone Growth.

    PubMed

    Amso, Zaid; Cornish, Jillian; Brimble, Margaret A

    2016-07-01

    Loss of bone occurs in the age-related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone-anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone-anabolic drug is available in the market. The discovery of more novel, cost-effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone-anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone-anabolic peptides, and their development for promoting bone growth.

  16. Ecdysteroids: A novel class of anabolic agents?

    PubMed Central

    Botrè, F; Naß, A; Hengevoss, J; Diel, P; Wolber, G

    2015-01-01

    Increasing numbers of dietary supplements with ecdysteroids are marketed as “natural anabolic agents”. Results of recent studies suggested that their anabolic effect is mediated by estrogen receptor (ER) binding. Within this study the anabolic potency of ecdysterone was compared to well characterized anabolic substances. Effects on the fiber sizes of the soleus muscle in rats as well the diameter of C2C12 derived myotubes were used as biological readouts. Ecdysterone exhibited a strong hypertrophic effect on the fiber size of rat soleus muscle that was found even stronger compared to the test compounds metandienone (dianabol), estradienedione (trenbolox), and SARM S 1, all administered in the same dose (5 mg/kg body weight, for 21 days). In C2C12 myotubes ecdysterone (1 µM) induced a significant increase of the diameter comparable to dihydrotestosterone (1 µM) and IGF 1 (1.3 nM). Molecular docking experiments supported the ERβ mediated action of ecdysterone. To clarify its status in sports, ecdysterone should be considered to be included in the class “S1.2 Other Anabolic Agents” of the list of prohibited substances of the World Anti-Doping Agency. PMID:26060342

  17. Pathological changes in anabolic androgenic steroid users.

    PubMed

    Lusetti, Monia; Licata, Manuela; Silingardi, Enrico; Reggiani Bonetti, Luca; Palmiere, Cristian

    2015-07-01

    Several classes of recreational and prescription drugs have additional effects on the heart and vasculature, which may significantly contribute to morbidity and mortality in chronic users. The study presented herein focuses on pathological changes involving the heart possibly due to anabolic androgenic steroid use. The role these hormones may play in their occurrence of sudden cardiac death is also investigated. 98 medico-legal cases including 6 anabolic androgenic steroid users were retrospectively reviewed. Autopsies, histology, immunohistochemistry, biochemistry and toxicology were performed in all cases. Pathological changes consisted of various degrees of interstitial and perivascular fibrosis as well as fibroadipous metaplasia and perineural fibrosis within the myocardium of the left ventricle. Within the limits of the small number of investigated cases, our results appear to confirm former observations on this topic and suggest anabolic androgenic steroid's potential causative role in the pathogenesis of sudden cardiac deaths in chronic users.

  18. Anabolic-androgenic steroids and related substances.

    PubMed

    Yesalis, Charles E; Bahrke, Michael S

    2002-08-01

    Testosterone is the primary male sex hormone, and anabolic-androgenic steroids are synthetic derivatives of testosterone. Anabolic steroids are used to enhance athletic performance and appearance. Adverse effects include those on the liver, serum lipids, psyche/behavior, and the reproductive system. Androstenedione is an anabolic-androgenic steroid used to increase blood testosterone levels for the purposes of increasing strength, lean body mass, and sexual performance. However, there is no research indicating androstenedione or its related compounds, significantly increases strength and/or lean body mass by increasing testosterone levels. The long-term health effects of prolonged androstenedione supplementation are unknown. Dehydroepiandrosterone (DHEA) is a weak androgen also used to elevate testosterone levels. DHEA is also advertised as an antiobesity and antiaging supplement capable of improving libido, vitality, and immunity levels. However, research demonstrates that DHEA supplementation does not increase serum testosterone concentrations or increase strength in men, and it may have virilizing effects on women.

  19. Sexual functioning of male anabolic steroid abusers.

    PubMed

    Moss, H B; Panzak, G L; Tarter, R E

    1993-02-01

    The effects of anabolic steroid use on male sexual behavior were assessed using a structured clinical interview administered to male body builders currently using steroids, and to two comparison groups (body builders with a past but not current history of steroid use, and a group of "natural" body builders who had never used steroids). Current anabolic steroid users had a significantly higher coital and orgasmic frequency than did comparison athletes. They also reported a significantly higher incidence of erectile difficulties during the past month. Beliefs concerning the sexually stimulating effects of steroids did not correlate with the frequencies of specific sexual behaviors. The data support the contention that anabolic steroids, as androgenic compounds, enhance sexual desire.

  20. Anabolic steroids: implications for the nurse practitioner.

    PubMed

    Duncan, D J; Shaw, E B

    1985-12-01

    Anabolic steroids are being used by athletes in a wide variety of sports in efforts to enhance their athletic performances. Steroid abuse is complex to evaluate due to the highly emotional subject matter and the limitations in researching anabolic steroids. This article has been written to heighten the practitioner's awareness of the problem of "sports doping" with anabolic steroids. It will provide practical information on possible consequences of steroid use and outline essential information to obtain through the history, physical exam and laboratory studies. Intervention strategies based on the three levels of prevention are described. With awareness of the problem of sports doping and knowledge of how to deal with it in primary care, the nurse practitioner can enhance the health care provided to aspiring athletes, athletes and retired athletes.

  1. Direct determination of anabolic steroids in pig urine by a new SPME-GC-MS method.

    PubMed

    Zhang, Zhuomin; Duan, Hongbin; Zhang, Lan; Chen, Xi; Liu, Wei; Chen, Guonan

    2009-05-15

    A new solid phase microextraction (SPME) method coupled with gas chromatography-mass spectrometry (GC-MS) was developed for rapid determination of four anabolic steroids such as 3alpha-hydroxy-5alpha-androstane-17-one (HA), dihydrotestosterone (DHT), androstenedione (AD) and methyltestosterone (MT) in pig urine. SPME was used to extract the four anabolic compounds directly without derivatization. The optimum SPME sampling conditions were based on the home-made carbowax-divinylbenzene (CW-DVB) fiber coating during extraction at 40 degrees C for 50 min with 0.18 g/mL NaCl solution and 750 rpm stirring speed. The linear ranges of the proposed method were in the range of 8-640 pg/mL for HA and DHT and 16-510 pg/mL for AD and MT, respectively. The detection limits (S/N=3) were from 2 to 8 pg/mL for the four anabolic steroids. This SPME method provided very high enrichment factors for the four anabolic steroids, which were 1063-fold and 965-fold for HA and DHT at the concentration of 8 pg/mL and 207-fold and 451-fold for AD and MT at the concentration of 16 pg/mL, respectively. The recoveries ranged from 71.3 to 121%, and the RSDs were lower than 12.9%. The method was sensitive and reliable for determination of trace anabolic steroids in biological samples.

  2. PTH Promotes Bone Anabolism by Stimulating Aerobic Glycolysis via IGF Signaling.

    PubMed

    Esen, Emel; Lee, Seung-Yon; Wice, Burton M; Long, Fanxin

    2015-11-01

    Teriparatide, a recombinant peptide corresponding to amino acids 1-34 of human parathyroid hormone (PTH), has been an effective bone anabolic drug for over a decade. However, the mechanism whereby PTH stimulates bone formation remains incompletely understood. Here we report that in cultures of osteoblast-lineage cells, PTH stimulates glucose consumption and lactate production in the presence of oxygen, a hallmark of aerobic glycolysis, also known as Warburg effect. Experiments with radioactively labeled glucose demonstrate that PTH suppresses glucose entry into the tricarboxylic acid cycle (TCA cycle). Mechanistically, the increase in aerobic glycolysis is secondary to insulin-like growth factor (Igf) signaling induced by PTH, whereas the metabolic effect of Igf is dependent on activation of mammalian target of rapamycin complex 2 (mTORC2). Importantly, pharmacological perturbation of glycolysis suppresses the bone anabolic effect of intermittent PTH in the mouse. Thus, stimulation of aerobic glycolysis via Igf signaling contributes to bone anabolism in response to PTH.

  3. Fatal Liver Cyst Rupture Due to Anabolic Steroid Use: A Case Presentation.

    PubMed

    Hansma, Patrick; Diaz, Francisco J; Njiwaji, Chantel

    2016-03-01

    Liver cysts are commonly found incidentally from imaging scans or at autopsy. These benign neoplasms vary in size and represent a heterogeneous group of disorders, for which the demographics, risk factors, apparent inciting event, clinical presentation, and outcome are varied. Complications that can develop from a liver cyst include development of spontaneous hemorrhage, infection, and/or obstruction. Although the etiology of liver cysts varies, fatal rupture of a hemorrhagic liver cyst due to anabolic steroid use is a rare occurrence. In fact, there are few reported cases in journal literature. We report a case of a fatal liver cyst rupture with resultant hemoperitoneum in the presence of anabolic steroid (stanozolol) use.

  4. Review of Androgenic Anabolic Steroid Use

    SciTech Connect

    T. Borges; G. Eisele; C. Byrd

    2001-07-31

    An area that has been overlooked within personnel security evaluations is employee use of androgenic-anabolic steroids (AAS). Current drug testing within the federal government does not include testing for anabolic steroids, and the difficulties to implement such testing protocols-not to mention the cost involved-make AAS testing highly improbable. The basis of this report is to bring to the forefront the damage that anabolic steroids can cause from both a physical and a psychological standpoint. Most individuals who use AASs do so to increase their muscle mass because they wish to gain some type of competitive edge during athletic competition or they wish to enhance their physical features for self-satisfaction and self-esteem (i.e., body building). Security officers are one group of men who often take high doses of anabolic steroids, according to the Second Report of the Senate Standing Committee (1990). The negative psychological characteristics for AAS use is extensive and includes prominent hostility, aggressiveness, irritability, euphoria, grandiose beliefs, hyperactivity, reckless behavior, increased sexual appetite, unpredictability, poor impulse control, mood fluctuations, and insomnia. The drug may invoke a sense of power and invincibility (Leckman and Scahill, 1990). Depressive symptoms, such as anhedonia, fatigue, impaired concentration, decreased libido, and even suicidality (Pope and Katz, 1992) have been noted with steroid withdrawal. It appears that long-term users of AAS experience similar characteristics as other substance abusers (i.e., craving, dependence, and withdrawal symptoms).

  5. Anabolic androgenic steroid-induced Takotsubo cardiomyopathy

    PubMed Central

    Sella, Gianluigi; Bellanti, Giancarlo; Margheri, Massimo

    2015-01-01

    Anabolic steroid abuse, aimed at increasing muscle mass, has been growing in recent years. We describe a case of a 25-year-old bodybuilder who, after taking nandrolone and stanozolol, presented with Takotsubo syndrome. The angiography showed a normal coronary anatomy with the absence of stenosis. The left ventricular function was completely normalised after 1 week. PMID:25804946

  6. Preventing Anabolic Steroid Use: Guidelines and Activities.

    ERIC Educational Resources Information Center

    Nutter, June; Rauhe, Betty

    1997-01-01

    Information about anabolic steroids should be included in the school health curriculum as early as possible. The paper presents suggestions for planning education programs and offers a variety of activities and strategies appropriate for many age groups, including case studies, story completion, posters, demonstrations, projects, creative writing,…

  7. Ethylene Response Factors: A Key Regulatory Hub in Hormone and Stress Signaling.

    PubMed

    Müller, Maren; Munné-Bosch, Sergi

    2015-09-01

    Ethylene is essential for many developmental processes and a key mediator of biotic and abiotic stress responses in plants. The ethylene signaling and response pathway includes Ethylene Response Factors (ERFs), which belong to the transcription factor family APETALA2/ERF. It is well known that ERFs regulate molecular response to pathogen attack by binding to sequences containing AGCCGCC motifs (the GCC box), a cis-acting element. However, recent studies suggest that several ERFs also bind to dehydration-responsive elements and act as a key regulatory hub in plant responses to abiotic stresses. Here, we review some of the recent advances in our understanding of the ethylene signaling and response pathway, with emphasis on ERFs and their role in hormone cross talk and redox signaling under abiotic stresses. We conclude that ERFs act as a key regulatory hub, integrating ethylene, abscisic acid, jasmonate, and redox signaling in the plant response to a number of abiotic stresses.

  8. Ethylene Response Factors: A Key Regulatory Hub in Hormone and Stress Signaling1

    PubMed Central

    Müller, Maren; Munné-Bosch, Sergi

    2015-01-01

    Ethylene is essential for many developmental processes and a key mediator of biotic and abiotic stress responses in plants. The ethylene signaling and response pathway includes Ethylene Response Factors (ERFs), which belong to the transcription factor family APETALA2/ERF. It is well known that ERFs regulate molecular response to pathogen attack by binding to sequences containing AGCCGCC motifs (the GCC box), a cis-acting element. However, recent studies suggest that several ERFs also bind to dehydration-responsive elements and act as a key regulatory hub in plant responses to abiotic stresses. Here, we review some of the recent advances in our understanding of the ethylene signaling and response pathway, with emphasis on ERFs and their role in hormone cross talk and redox signaling under abiotic stresses. We conclude that ERFs act as a key regulatory hub, integrating ethylene, abscisic acid, jasmonate, and redox signaling in the plant response to a number of abiotic stresses. PMID:26103991

  9. Myopic Loss Aversion: Demystifying the Key Factors Influencing Decision Problem Framing

    ERIC Educational Resources Information Center

    Hardin, Andrew M.; Looney, Clayton Arlen

    2012-01-01

    Advancement of myopic loss aversion theory has been hamstrung by conflicting results, methodological inconsistencies, and a piecemeal approach toward understanding the key factors influencing decision problem framing. A series of controlled experiments provides a more holistic view of the variables promoting myopia. Extending the information…

  10. Understanding Reusability as a Key Factor for Open Education: A Review

    ERIC Educational Resources Information Center

    Chiappe, Andres; Arias, Vivian

    2015-01-01

    This article describes both the process and the results of an extensive literature review on "reusability" as one of the key factors for the creation of open content in the context of open and distance learning. Qualitative analysis of texts was made from 1992 to early 2014 in order to identify meanings associated with reusability and…

  11. Agri-Environmental Resource Management by Large-Scale Collective Action: Determining KEY Success Factors

    ERIC Educational Resources Information Center

    Uetake, Tetsuya

    2015-01-01

    Purpose: Large-scale collective action is necessary when managing agricultural natural resources such as biodiversity and water quality. This paper determines the key factors to the success of such action. Design/Methodology/Approach: This paper analyses four large-scale collective actions used to manage agri-environmental resources in Canada and…

  12. Epigenetic Regulation of Chondrocyte Catabolism and Anabolism in Osteoarthritis.

    PubMed

    Kim, Hyeonkyeong; Kang, Donghyun; Cho, Yongsik; Kim, Jin-Hong

    2015-08-01

    Osteoarthritis (OA) is one of the most prevalent forms of joint disorder, associated with a tremendous socioeconomic burden worldwide. Various non-genetic and lifestyle-related factors such as aging and obesity have been recognized as major risk factors for OA, underscoring the potential role for epigenetic regulation in the pathogenesis of the disease. OA-associated epigenetic aberrations have been noted at the level of DNA methylation and histone modification in chondrocytes. These epigenetic regulations are implicated in driving an imbalance between the expression of catabolic and anabolic factors, leading eventually to osteoarthritic cartilage destruction. Cellular senescence and metabolic abnormalities driven by OA-associated risk factors appear to accompany epigenetic drifts in chondrocytes. Notably, molecular events associated with metabolic disorders influence epigenetic regulation in chondrocytes, supporting the notion that OA is a metabolic disease. Here, we review accumulating evidence supporting a role for epigenetics in the regulation of cartilage homeostasis and OA pathogenesis.

  13. Hidden Danger of Irrational Abusing Illegal Androgenic-anabolic Steroids in Recreational Athletes Age Under 35 in Bosnia & Herzegovina

    PubMed Central

    Solakovic, Sid; Totic, Dragan; Vukas, Haris; Djedovic, Muhamed

    2015-01-01

    Introduction: Androgenic-anabolic steroids are rarely used by sportsmen who want to improve physical performance in competition sport. Despite that they are well aware of the side effects of anabolic steroids, many young athletes in Bosnia and Herzegovina without competition motivation come in temptation, trying to achieve better muscle proportion and physical performance unknowing consequence of side effects and what is hiding behind. Risk factors such as increasing of lipid levels and arterial hypertension are major factors which have important role in the Pathogenesis of atherosclerosis and are responsible for occurrence of cardiovascular disease even causing a sudden death in young athletes. Objective: The aim of the study was to estimate the frequency of misusing of androgenic anabolic steroid drugs in young recreational sportsmen without competition motivation. This study will try to estimate vascular and lipid status, analyzing the side effects of steroids in young recreational athletes under the age of 35, in Bosnia and Herzegovina. Methods: The study included 70 individuals in period of 2010 till 2015 on recreational exercising program; 35 individuals misusing androgenic anabolic steroids during the period of 5 years were compared with 35 individuals which do not use androgenic anabolic steroids. Non-invasive methods were used in all individual (clinical examination and vascular ultrasound examination of vein system). The routine of training units in both groups was approximately two hours 4-6 times per week. Results: Final analysis has reveal that in androgenic anabolic steroids group in 18 individuals or 55.7% arterial hypertension with hyperlipidemia was more represented, compared with the group without using anabolic steroids, represented by 2 individuals or 5.7% and it was statistically considered significant by using p value less than 0.05. (p<0.05). Statistically dominant population using anabolic steroids drugs are males (100%) or 35 individuals

  14. Determinants of Anabolic-Androgenic Steroid Risk Perceptions in Youth Populations: A Multivariate Analysis

    ERIC Educational Resources Information Center

    Denham, Bryan E.

    2009-01-01

    Grounded conceptually in social cognitive theory, this research examines how personal, behavioral, and environmental factors are associated with risk perceptions of anabolic-androgenic steroids. Ordinal logistic regression and logit log-linear models applied to data gathered from high-school seniors (N = 2,160) in the 2005 Monitoring the Future…

  15. Key factors of readiness in the implementation of industrialised building system (IBS)

    NASA Astrophysics Data System (ADS)

    Tamrin, Norhidayah; Nawi, Mohd Nasrun Mohd; Nifa, Faizatul Akmar Abdul

    2016-08-01

    Although IBS has been introduced since the 1960, and many advantages that have identified for the implementation of IBS in Malaysia, yet the level of implementation of IBS still did not achieve the government target. Previous studies have been conducted to identify the factors that contribute to the lack of the implementation. From the previous studies, mostly the barriers of IBS implementation are rooted within the several semi-structured lack of readiness among industry players. The interview participants for this study are from the multidisciplinary IBS practitioners. This paper discusses the identified readiness with the objective to determine what the key factor of readiness in IBS implementation is and how far the factors influence the IBS activities. From the finding, the readiness factor was divided into three main factors which are knowledge, ability and planning.

  16. Identifying Key Drivers of Return Reversal with Dynamical Bayesian Factor Graph

    PubMed Central

    Zhao, Shuai; Tong, Yunhai; Wang, Zitian; Tan, Shaohua

    2016-01-01

    In the stock market, return reversal occurs when investors sell overbought stocks and buy oversold stocks, reversing the stocks’ price trends. In this paper, we develop a new method to identify key drivers of return reversal by incorporating a comprehensive set of factors derived from different economic theories into one unified dynamical Bayesian factor graph. We then use the model to depict factor relationships and their dynamics, from which we make some interesting discoveries about the mechanism behind return reversals. Through extensive experiments on the US stock market, we conclude that among the various factors, the liquidity factors consistently emerge as key drivers of return reversal, which is in support of the theory of liquidity effect. Specifically, we find that stocks with high turnover rates or high Amihud illiquidity measures have a greater probability of experiencing return reversals. Apart from the consistent drivers, we find other drivers of return reversal that generally change from year to year, and they serve as important characteristics for evaluating the trends of stock returns. Besides, we also identify some seldom discussed yet enlightening inter-factor relationships, one of which shows that stocks in Finance and Insurance industry are more likely to have high Amihud illiquidity measures in comparison with those in other industries. These conclusions are robust for return reversals under different thresholds. PMID:27893780

  17. Identifying Key Drivers of Return Reversal with Dynamical Bayesian Factor Graph.

    PubMed

    Zhao, Shuai; Tong, Yunhai; Wang, Zitian; Tan, Shaohua

    2016-01-01

    In the stock market, return reversal occurs when investors sell overbought stocks and buy oversold stocks, reversing the stocks' price trends. In this paper, we develop a new method to identify key drivers of return reversal by incorporating a comprehensive set of factors derived from different economic theories into one unified dynamical Bayesian factor graph. We then use the model to depict factor relationships and their dynamics, from which we make some interesting discoveries about the mechanism behind return reversals. Through extensive experiments on the US stock market, we conclude that among the various factors, the liquidity factors consistently emerge as key drivers of return reversal, which is in support of the theory of liquidity effect. Specifically, we find that stocks with high turnover rates or high Amihud illiquidity measures have a greater probability of experiencing return reversals. Apart from the consistent drivers, we find other drivers of return reversal that generally change from year to year, and they serve as important characteristics for evaluating the trends of stock returns. Besides, we also identify some seldom discussed yet enlightening inter-factor relationships, one of which shows that stocks in Finance and Insurance industry are more likely to have high Amihud illiquidity measures in comparison with those in other industries. These conclusions are robust for return reversals under different thresholds.

  18. Factors Influencing Oral Bioavailability of Thai Mango Seed Kernel Extract and Its Key Phenolic Principles.

    PubMed

    Jiamboonsri, Pimsumon; Pithayanukul, Pimolpan; Bavovada, Rapepol; Leanpolchareanchai, Jiraporn; Yin, Taijun; Gao, Song; Hu, Ming

    2015-11-30

    Mango seed kernel extract (MSKE) and its key components (gallic acid, GA; methyl gallate, MG; and pentagalloyl glucopyranose, PGG) have generated interest because of their pharmacological activities. To develop the potential use of the key components in MSKE as natural therapeutic agents, their pharmacokinetic data are necessary. Therefore, this study was performed to evaluate the factors affecting their oral bioavailability as pure compounds and as components in MSKE. The in vitro chemical stability, biological stability, and absorption were evaluated in Hanks' Balanced Salt Solution, Caco-2 cell and rat fecal lysates, and the Caco-2 cell model, respectively. The in vivo oral pharmacokinetic behavior was elucidated in Sprague-Dawley rats. The key components were unstable under alkaline conditions and in Caco-2 cell lysates or rat fecal lysates. The absorptive permeability coefficient followed the order MG > GA > PGG. The in vivo results exhibited similar pharmacokinetic trends to the in vitro studies. Additionally, the co-components in MSKE may affect the pharmacokinetic behaviors of the key components in MSKE. In conclusion, chemical degradation under alkaline conditions, biological degradation by intestinal cell and colonic microflora enzymes, and low absorptive permeability could be important factors underlying the oral bioavailability of these polyphenols.

  19. Three-factor anonymous authentication and key agreement scheme for Telecare Medicine Information Systems.

    PubMed

    Arshad, Hamed; Nikooghadam, Morteza

    2014-12-01

    Nowadays, with comprehensive employment of the internet, healthcare delivery services is provided remotely by telecare medicine information systems (TMISs). A secure mechanism for authentication and key agreement is one of the most important security requirements for TMISs. Recently, Tan proposed a user anonymity preserving three-factor authentication scheme for TMIS. The present paper shows that Tan's scheme is vulnerable to replay attacks and Denial-of-Service attacks. In order to overcome these security flaws, a new and efficient three-factor anonymous authentication and key agreement scheme for TMIS is proposed. Security and performance analysis shows superiority of the proposed scheme in comparison with previously proposed schemes that are related to security of TMISs.

  20. Use of anabolic-androgenic steroids masking the diagnosis of pleural tuberculosis: a case report

    PubMed Central

    2009-01-01

    Introduction Tuberculous pleural effusions are not always easy to diagnose but the presence of a lymphocyte-rich exudate associated with an increased adenosine deaminase level and a positive skin test result are highly sensitive diagnostic signs. Case presentation We report a case of pleural tuberculosis in a 31-year-old white male patient from Caracas, Venezuela who was negative for human immunodeficiency virus and presented 2 weeks after injecting the anabolic-androgenic steroid nandrolone decanoate, in whom all the tests for tuberculosis were initially negative; an eosinophilic pleural effusion with a low adenosine deaminase level, a negative tuberculin skin test and negative for acid-fast bacilli staining and culture of the pleural fluid. After excluding other causes of eosinophilic pleural effusion malignant pleural effusion was suspected. The patient did not return until 4 months later. The second thoracentesis obtained a pleural fluid suggestive for tuberculosis, with a predominance of lymphocytes, an elevated adenosine deaminase level (51 U/l) and a positive tuberculin skin test. Culture of pleural fragments confirmed pleural tuberculosis. Conclusion This case suggests that the use of an anabolic-androgenic steroid masks the definitive diagnosis of pleural tuberculosis by changing the key diagnostic parameters of the pleural fluid, a finding not previously reported. Available evidence of the effects of anabolic steroids on the immune system also suggests that patients using anabolic-androgenic steroids might be susceptible to developing tuberculosis in either reactivating a latent infection or facilitating development of the disease after a recent infection. PMID:19175931

  1. Anabolic steroid-induced hypogonadism--towards a unified hypothesis of anabolic steroid action.

    PubMed

    Tan, R S; Scally, M C

    2009-06-01

    Anabolic steroid-induced hypogonadism (ASIH) is the functional incompetence of the testes with subnormal or impaired production of testosterone and/or spermatozoa due to administration of androgens or anabolic steroids. Anabolic-androgenic steroid (AAS), both prescription and nonprescription, use is a cause of ASIH. Current AAS use includes prescribing for wasting associated conditions. Nonprescription AAS use is also believed to lead to AAS dependency or addiction. Together these two uses account for more than four million males taking AAS in one form or another for a limited duration. While both of these uses deal with the effects of AAS administration they do not account for the period after AAS cessation. The signs and symptoms of ASIH directly impact the observation of an increase in muscle mass and muscle strength from AAS administration and also reflect what is believed to demonstrate AAS dependency. More significantly, AAS prescribing after cessation adds the comorbid condition of hypogonadism to their already existing chronic illness. ASIH is critical towards any future planned use of AAS or similar compound to effect positive changes in muscle mass and muscle strength as well as an understanding for what has been termed anabolic steroid dependency. The further understanding and treatments that mitigate or prevent ASIH could contribute to androgen therapies for wasting associated diseases and stopping nonprescription AAS use. This paper proposes a unified hypothesis that the net effects for anabolic steroid administration must necessarily include the period after their cessation or ASIH.

  2. [Dehydroepiandrosterone [DHEA(S)]: anabolic hormone?].

    PubMed

    Luci, Michele; Valenti, Giorgio; Maggio, Marcello

    2010-09-01

    The role of dehydroepiandrosterone (DHEA) and its sulphated form (DHEAS) as anabolic hormones is still debated in the literature. In this review we describe the fundamental steps of DHEA physiological secretion and its peripheral metabolism. Moreover we will list all the observational and intervention studies conducted in humans. Many observational studies have tested the relationship between low DHEA levels and age-related changes in skeletal muscle and bone, while intervention studies underline the positive and significant effects of DHEA treatment on several parameters of body composition. Surprisingly, observational studies are not consistent with different effects in men and women. There is recent evidence of a significant role of DHEA in frailty syndrome and as predictor of mortality. However a more complete approach of the problem suggests the opportunity to not focus only on one single hormonal derangement but to analyze the parallel dysregulation of anabolic hormones including sex steroids, GH-IGF-1 system and other catabolic hormones.

  3. Key success factors for clinical knowledge management systems: Comparing physician and hospital manager viewpoints.

    PubMed

    Chang, Sho-Fang; Hsieh, Ping-Jung; Chen, Hui-Fang

    2015-01-01

    The study explores the perceptions of physicians and hospital managers regarding the key success factors (KSFs) of a clinical knowledge management system (CKMS). It aims to eliminate the perception gap and gain more insights for a successful CKMS.A survey was conducted in four medical centers in Taiwan. A total of 340 questionnaires, including 15 for hospital managers and 70 for physicians in each hospital, were administered. The effective response rates are 78.3% and 56.1% respectively. Partial least square (PLS) were used to analyze the data.The results identified six KSFs of CKMS including system software and hardware, knowledge quality, system quality, organizational factors, user satisfaction, and policy factors. User satisfaction and policy factors have direct effects on perceived CKMS performance. Knowledge quality is regarded as an antecedent to user satisfaction, while system quality is the antecedent to both user satisfaction and policy factors. System software and hardware was supported only by managers, and organizational factors were supported only by physicians.Among the factors, this study highlighted the policy factor. Besides, the study provides hospital managers additional insights into physician requirements for organizational support. Third, more physician participation and involvement are recommended when introducing and developing a CKMS.

  4. Consequences of use of anabolic androgenic steroids.

    PubMed

    Casavant, Marcel J; Blake, Kathleen; Griffith, Jill; Yates, Andrew; Copley, LaRae M

    2007-08-01

    Whether providing anticipatory guidance to the young adolescent patient, conducting a preparticipation examination on a young athlete, or treating a sick user of anabolic androgenic steroids (AASs), the primary care physician must be familiar with the adverse consequences of the use of these compounds. This article reviews the endocrine, cardiovascular, neuropsychiatric, musculoskeletal, hematologic, hepatic, and miscellaneous effects of AASs, highlighting effects reported in children and adolescents, and relying on consequences in adults when pediatric data is unavailable.

  5. Identifying the key factors affecting warning message dissemination in VANET real urban scenarios.

    PubMed

    Fogue, Manuel; Garrido, Piedad; Martinez, Francisco J; Cano, Juan-Carlos; Calafate, Carlos T; Manzoni, Pietro

    2013-04-19

    In recent years, new architectures and technologies have been proposed for Vehicular Ad Hoc networks (VANETs). Due to the cost and complexity of deploying such networks, most of these proposals rely on simulation. However, we find that most of the experiments made to validate these proposals tend to overlook the most important and representative factors. Moreover, the scenarios simulated tend to be very simplistic (highways or Manhattan-based layouts), which could seriously affect the validity of the obtained results. In this paper, we present a statistical analysis based on the 2k factorial methodology to determine the most representative factors affecting traffic safety applications under real roadmaps. Our purpose is to determine which are the key factors affecting Warning Message Dissemination in order to concentrate research tests on such parameters, thus avoiding unnecessary simulations and reducing the amount of simulation time required. Simulation results show that the key factors affecting warning messages delivery are the density of vehicles and the roadmap used. Based on this statistical analysis, we consider that VANET researchers must evaluate the benefits of their proposals using different vehicle densities and city scenarios, to obtain a broad perspective on the effectiveness of their solution. Finally, since city maps can be quite heterogeneous, we propose a roadmap profile classification to further reduce the number of cities evaluated.

  6. Psychological factors mediate key symptoms of fibromyalgia through their influence on stress.

    PubMed

    Malin, Katrina; Littlejohn, Geoffrey Owen

    2016-09-01

    The clinical features of fibromyalgia are associated with various psychological factors, including stress. We examined the hypothesis that the path that psychological factors follow in influencing fibromyalgia symptoms is through their direct effect on stress. Ninety-eight females with ACR 1990 classified fibromyalgia completed the following questionnaires: The Big 5 Personality Inventory, Fibromyalgia Impact Questionnaire, Perceived Stress Scale, Profile of Mood States, Mastery Scale, and Perceived Control of Internal States Scale. SPSS (PASW version 22) was used to perform basic t tests, means, and standard deviations to show difference between symptom characteristics. Pathway analysis using structural equation modelling (Laavan) examined the effect of stress on the relationships between psychological factors and the elements that define the fibromyalgia phenotype. The preferred model showed that the identified path clearly linked the psychological variables of anxiety, neuroticism and mastery, but not internal control, to the three key elements of fibromyalgia, namely pain, fatigue and sleep (p < 0.001), via the person's perceived stress. Confusion, however, did not fit the preferred model. This study confirms that stress is a necessary link in the pathway between certain identified, established and significant psychological factors and key fibromyalgia symptoms. This has implications for the understanding of contributing mechanisms and the clinical care of patients with fibromyalgia.

  7. Identifying the Key Factors Affecting Warning Message Dissemination in VANET Real Urban Scenarios

    PubMed Central

    Fogue, Manuel; Garrido, Piedad; Martinez, Francisco J.; Cano, Juan-Carlos; Calafate, Carlos T.; Manzoni, Pietro

    2013-01-01

    In recent years, new architectures and technologies have been proposed for Vehicular Ad Hoc networks (VANETs). Due to the cost and complexity of deploying such networks, most of these proposals rely on simulation. However, we find that most of the experiments made to validate these proposals tend to overlook the most important and representative factors. Moreover, the scenarios simulated tend to be very simplistic (highways or Manhattan-based layouts), which could seriously affect the validity of the obtained results. In this paper, we present a statistical analysis based on the 2k factorial methodology to determine the most representative factors affecting traffic safety applications under real roadmaps. Our purpose is to determine which are the key factors affecting Warning Message Dissemination in order to concentrate research tests on such parameters, thus avoiding unnecessary simulations and reducing the amount of simulation time required. Simulation results show that the key factors affecting warning messages delivery are the density of vehicles and the roadmap used. Based on this statistical analysis, we consider that VANET researchers must evaluate the benefits of their proposals using different vehicle densities and city scenarios, to obtain a broad perspective on the effectiveness of their solution. Finally, since city maps can be quite heterogeneous, we propose a roadmap profile classification to further reduce the number of cities evaluated. PMID:23604026

  8. A key genetic factor for fucosyllactose utilization affects infant gut microbiota development

    PubMed Central

    Matsuki, Takahiro; Yahagi, Kana; Mori, Hiroshi; Matsumoto, Hoshitaka; Hara, Taeko; Tajima, Saya; Ogawa, Eishin; Kodama, Hiroko; Yamamoto, Kazuya; Yamada, Takuji; Matsumoto, Satoshi; Kurokawa, Ken

    2016-01-01

    Recent studies have demonstrated that gut microbiota development influences infants' health and subsequent host physiology. However, the factors shaping the development of the microbiota remain poorly understood, and the mechanisms through which these factors affect gut metabolite profiles have not been extensively investigated. Here we analyse gut microbiota development of 27 infants during the first month of life. We find three distinct clusters that transition towards Bifidobacteriaceae-dominant microbiota. We observe considerable differences in human milk oligosaccharide utilization among infant bifidobacteria. Colonization of fucosyllactose (FL)-utilizing bifidobacteria is associated with altered metabolite profiles and microbiota compositions, which have been previously shown to affect infant health. Genome analysis of infants' bifidobacteria reveals an ABC transporter as a key genetic factor for FL utilization. Thus, the ability of bifidobacteria to utilize FL and the presence of FL in breast milk may affect the development of the gut microbiota in infants, and might ultimately have therapeutic implications. PMID:27340092

  9. Identification of Key Transcription Factors Associated with Lung Squamous Cell Carcinoma

    PubMed Central

    Zhang, Feng; Chen, Xia; Wei, Ke; Liu, Daoming; Xu, Xiaodong; Zhang, Xing; Shi, Hong

    2017-01-01

    Background Lung squamous cell carcinoma (lung SCC) is a common type of lung cancer, but its mechanism of pathogenesis is unclear. The aim of this study was to identify key transcription factors in lung SCC and elucidate its mechanism. Material/Methods Six published microarray datasets of lung SCC were downloaded from Gene Expression Omnibus (GEO) for integrated bioinformatics analysis. Significance analysis of microarrays was used to identify differentially expressed genes (DEGs) between lung SCC and normal controls. The biological functions and signaling pathways of DEGs were mapped in the Gene Otology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, respectively. A transcription factor gene regulatory network was used to obtain insights into the functions of DEGs. Results A total of 1,011 genes, including 539 upregulated genes and 462 downregulated genes, were filtered as DEGs between lung SCC and normal controls. DEGs were significantly enriched in cell cycle, DNA replication, p53 signaling pathway, pathways in cancer, adherens junction, and cell adhesion molecules signaling pathways. There were 57 transcription factors identified, which were used to construct a regulatory network. The network consisted of 736 interactions between 49 transcription factors and 486 DEGs. NFIC, BRCA1, and NFATC2 were the top 3 transcription factors that had the highest connectivity with DEGs and that regulated 83, 82, and 75 DEGs in the network, respectively. Conclusions NFIC, BRCA1, and NFATC2 might be the key transcription factors in the development of lung SCC by regulating the genes involved in cell cycle and DNA replication pathways. PMID:28081052

  10. Vascular endothelial growth factor and other angioglioneurins: key molecules in brain development and restoration.

    PubMed

    Lafuente, José Vicente; Ortuzar, Naiara; Bengoetxea, Harkaitz; Bulnes, Susana; Argandoña, Enrike G

    2012-01-01

    Angioneurines are a family of molecules that include vascular growth factors such as VEGF, neurotrophins such as BDNF, IGF-I, and Erythropoietin, among others. They affect both neural and vascular processes. Due to the fact that all of them act over glia, we propose the term angioglioneurins to name them. They play a key role in the neurogliovascular unit that represents the functional core maintaining BBB. Although delivery to CNS is still an unsolved problem nowadays, exogenous angioglioneurin administration represents a promising therapeutic strategy for many neurological pathologies due to their neurotrophic and neurogenic role. In brains, VEGF is produced by neurons and astrocytes in different stages and situation, binding to tyrosine kinase receptors and also to neuropilin family. This fact reinforces its key role in the cross talk between neural and vascular development and activity. Angioglioneurins described in this report might become an important therapeutic resource in CNS restoration, especially in pathologies as stroke or traumatic brain injury.

  11. Review of key factors controlling engineered nanoparticle transport in porous media.

    PubMed

    Wang, Mei; Gao, Bin; Tang, Deshan

    2016-11-15

    Nanotechnology, an emerging technology, has witnessed rapid development in production and application. Engineered nanomaterials revolutionize the industry due to their unique structure and superior performance. The release of engineered nanoparticles (ENPs) into the environment, however, may pose risks to the environment and public health. To advance current understanding of environmental behaviors of ENPs, this work provides an introductory overview of ENP fate and transport in porous media. It systematically reviews the key factors controlling their fate and transport in porous media. It first provides a brief overview of common ENPs in the environment and their sources. The key factors that govern ENP transport in porous media are then categorized into three groups: (1) nature of ENPs affecting their transport in porous media, (2) nature of porous media affecting ENP transport, and (3) nature of flow affecting ENP transport in porous media. In each group, findings in recent literature on the specific governing factors of ENP transport in porous media are discussed in details. Finally, this work concludes with remarks on the importance of ENP transport in porous media and directions for future research.

  12. Growth differentiation factor 5 is a key physiological regulator of dendrite growth during development.

    PubMed

    Osório, Catarina; Chacón, Pedro J; Kisiswa, Lilian; White, Matthew; Wyatt, Sean; Rodríguez-Tébar, Alfredo; Davies, Alun M

    2013-12-01

    Dendrite size and morphology are key determinants of the functional properties of neurons. Here, we show that growth differentiation factor 5 (GDF5), a member of the bone morphogenetic protein (BMP) subclass of the transforming growth factor β superfamily with a well-characterised role in limb morphogenesis, is a key regulator of the growth and elaboration of pyramidal cell dendrites in the developing hippocampus. Pyramidal cells co-express GDF5 and its preferred receptors, BMP receptor 1B and BMP receptor 2, during development. In culture, GDF5 substantially increased dendrite, but not axon, elongation from these neurons by a mechanism that depends on activation of SMADs 1/5/8 and upregulation of the transcription factor HES5. In vivo, the apical and basal dendritic arbours of pyramidal cells throughout the hippocampus were markedly stunted in both homozygous and heterozygous Gdf5 null mutants, indicating that dendrite size and complexity are exquisitely sensitive to the level of endogenous GDF5 synthesis.

  13. The development of focal segmental glomerulosclerosis secondary to anabolic steroid abuse.

    PubMed

    Harrington, Patrick; Ali, Galil; Chan, Anthony

    2011-12-02

    The authors present the case of a patient who presented to the nephrology department of a district general hospital with end-stage renal failure. He presented with malignant hypertension and symptoms and signs of uraemia. He also gave a history of prior abuse of anabolic steroids over a number of years. Renal biopsy was performed and the findings were in keeping with a diagnosis of advanced focal segmental glomerulosclerosis (FSGS). The patient went on to require renal replacement therapy within weeks of presentation. The authors suggest that anabolic steroid abuse is a direct cause of FSGS. People with raised body mass index are known to be at increased risk of developing this condition, due to increased haemodynamic stress on the glomeruli, with subsequent development of sclerosis. However, the authors believe that anabolic steroid abuse may be an independent risk factor, and that anabolic steroids have a direct nephrotoxic effect that leads to a more advanced initial presentation with rapid decline in renal function.

  14. Drug Insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging

    PubMed Central

    Bhasin, Shalender; Calof, Olga M; Storer, Thomas W; Lee, Martin L; Mazer, Norman A; Jasuja, Ravi; Montori, Victor M; Gao, Wenqing; Dalton, James T

    2007-01-01

    SUMMARY Several regulatory concerns have hindered development of androgens as anabolic therapies, despite unequivocal evidence that testosterone supplementation increases muscle mass and strength in men; it induces hypertrophy of type I and II muscle fibers, and increases myonuclear and satellite cell number. Androgens promote differentiation of mesenchymal multipotent cells into the myogenic lineage and inhibit their adipogenic differentiation, by facilitating association of androgen receptors with β-catenin and activating T-cell factor 4. Meta-analyses indicate that testosterone supplementation increases fat-free mass and muscle strength in HIV-positive men with weight loss, glucocorticoid-treated men, and older men with low or low-normal testosterone levels. The effects of testosterone on physical function and outcomes important to patients have not, however, been studied. In older men, increased hematocrit and increased risk of prostate biopsy and detection of prostate events are the most frequent, testosterone-related adverse events. Concerns about long-term risks have restrained enthusiasm for testosterone use as anabolic therapy. Selective androgen-receptor modulators that are preferentially anabolic and that spare the prostate hold promise as anabolic therapies. We need more studies to determine whether testosterone or selective androgen-receptor modulators can induce meaningful improvements in physical function and patient-important outcomes in patients with physical dysfunction associated with chronic illness or aging. PMID:16932274

  15. Modelling the anabolic response of bone using a cell population model.

    PubMed

    Buenzli, Pascal R; Pivonka, Peter; Gardiner, Bruce S; Smith, David W

    2012-08-21

    To maintain bone mass during bone remodelling, coupling is required between bone resorption and bone formation. This coordination is achieved by a network of autocrine and paracrine signalling molecules between cells of the osteoclastic lineage and cells of the osteoblastic lineage. Mathematical modelling of signalling between cells of both lineages can assist in the interpretation of experimental data, clarify signalling interactions and help develop a deeper understanding of complex bone diseases. Several mathematical models of bone cell interactions have been developed, some including RANK-RANKL-OPG signalling between cells and systemic parathyroid hormone PTH. However, to our knowledge these models do not currently include key aspects of some more recent biological evidence for anabolic responses. In this paper, we further develop a mathematical model of bone cell interactions by Pivonka et al. (2008) to include the proliferation of precursor osteoblasts into the model. This inclusion is important to be able to account for Wnt signalling, believed to play an important role in the anabolic responses of bone. We show that an increased rate of differentiation to precursor cells or an increased rate of proliferation of precursor osteoblasts themselves both result in increased bone mass. However, modelling these different processes separately enables the new model to represent recent experimental discoveries such as the role of Wnt signalling in bone biology and the recruitment of osteoblast progenitor cells by transforming growth factor β. Finally, we illustrate the power of the new model's capabilities by applying the model to prostate cancer metastasis to bone. In the bone microenvironment, prostate cancer cells are believed to release some of the same signalling molecules used to coordinate bone remodelling (i.e.,Wnt and PTHrP), enabling the cancer cells to disrupt normal signalling and coordination between bone cells. This disruption can lead to either bone

  16. Key Factors Influencing Rapid Development of Potentially Dune-Stabilizing Moss-Dominated Crusts.

    PubMed

    Bu, Chongfeng; Zhang, Kankan; Zhang, Chunyun; Wu, Shufang

    2015-01-01

    Biological soil crusts (BSCs) are a widespread photosynthetic ground cover in arid and semiarid areas. They have many positive ecological functions, such as increasing soil stability, and reducing water and wind erosion. Using artificial technology to achieve the rapid development of BSCs is expected to become a low-cost and highly beneficial ecological restoration measure. In the present study, typical moss-dominated crusts in a region characterized by mobile dunes (Mu Us Sandland, China) were collected, and a 40-day cultivation experiment was performed to investigate key factors, including watering frequency, light intensity and a nutrient addition, which affect the rapid development of moss crusts and their optimal combination. The results demonstrated that watering frequency and illumination had a significant positive effect (P=0.049, three-factor ANOVA) and a highly significant, complicated effect (P=0.000, three-factor ANOVA), respectively, on the plant density of bryophytes, and a highly significant positive effect on the chlorophyll a and exopolysaccharide contents (P=0.000, P=0.000; P=0.000, P=0.000; one-way ANOVA). Knop nutrient solution did not have a significant positive but rather negative effect on the promotion of moss-dominated crust development (P=0.270, three-factor ANOVA). Moss-dominated crusts treated with the combination of moderate-intensity light (6,000 lx) + high watering frequency (1 watering/2 days) - Knop had the highest moss plant densities, while the treatment with high-intensity light (12,000 lx) + high watering frequency (1 watering/2 days) + Knop nutrient solution had higher chlorophyll a contents than that under other treatments. It is entirely feasible to achieve the rapid development of moss crusts under laboratory conditions by regulating key factors and creating the right environment. Future applications may seek to use cultured bryophytes to control erosion in vulnerable areas with urgent needs.

  17. Key Factors Influencing Rapid Development of Potentially Dune-Stabilizing Moss-Dominated Crusts

    PubMed Central

    Bu, Chongfeng; Zhang, Kankan; Zhang, Chunyun; Wu, Shufang

    2015-01-01

    Biological soil crusts (BSCs) are a widespread photosynthetic ground cover in arid and semiarid areas. They have many positive ecological functions, such as increasing soil stability, and reducing water and wind erosion. Using artificial technology to achieve the rapid development of BSCs is expected to become a low-cost and highly beneficial ecological restoration measure. In the present study, typical moss-dominated crusts in a region characterized by mobile dunes (Mu Us Sandland, China) were collected, and a 40-day cultivation experiment was performed to investigate key factors, including watering frequency, light intensity and a nutrient addition, which affect the rapid development of moss crusts and their optimal combination. The results demonstrated that watering frequency and illumination had a significant positive effect (P=0.049, three-factor ANOVA) and a highly significant, complicated effect (P=0.000, three-factor ANOVA), respectively, on the plant density of bryophytes, and a highly significant positive effect on the chlorophyll a and exopolysaccharide contents (P=0.000, P=0.000; P=0.000, P=0.000; one-way ANOVA). Knop nutrient solution did not have a significant positive but rather negative effect on the promotion of moss-dominated crust development (P=0.270, three-factor ANOVA). Moss-dominated crusts treated with the combination of moderate-intensity light (6,000 lx) + high watering frequency (1 watering/2 days) - Knop had the highest moss plant densities, while the treatment with high-intensity light (12,000 lx) + high watering frequency (1 watering/2 days) + Knop nutrient solution had higher chlorophyll a contents than that under other treatments. It is entirely feasible to achieve the rapid development of moss crusts under laboratory conditions by regulating key factors and creating the right environment. Future applications may seek to use cultured bryophytes to control erosion in vulnerable areas with urgent needs. PMID:26230324

  18. Detection of key factors in the extraction and quantification of lycopene from tomato and tomato products.

    PubMed

    Periago, María Jesús; Rincón, Francisco; Jacob, Karin; García-Alonso, Javier; Ros, Gaspar

    2007-10-31

    The analytical process of lycopene extraction and photometrical determination was critically examined for raw tomato and processed tomato products by means of a 2 IV (15-10) Plackett-Burman experimental design in order to identify the key factors (KFs) involved. Fifteen apparent key factors (AKFs) reported in the literature were selected: sample weight (X1); volume of extraction solution (X2); antioxidant concentration (BHT, X3); neutralizing agent concentration (MgCO 3, X4); light presence during lycopene extraction (X5), homogenization velocity (X6) and time (X7), agitation time (X8), and temperature (X9) during the extraction process; water volume for separation of polar/nonpolar phases (X11); presence of inert atmosphere throughout the process (X12); time (X13), temperature (X14), and light presence (X10) during separation of phases and time delay for reading (X15). In general, higher lycopene concentrations in samples led to a higher number of key factors (KF). Thus, for raw tomato (lycopene range 1.22-2.29 mg/100 g) no KF were found, whereas for tomato sauce (lycopene range from 5.80 to 8.60 mg/100 g) one KF (X4) and for tomato paste (lycopene range from 35.80 to 51.27 mg/100 g) five KFs (X1, X2, X4, X11, and X12) were detected. For lycopene paste, X1 and X2 were identified as the KFs with the greatest impact on results, although in fact the X1/X2 ratio was the real cause. The results suggest that, with increased processing, the physical and chemical structure of lycopene becomes less important since the identified KFs explain almost 90% of variability in tomato paste but only 32% in raw tomato.

  19. Astragaloside IV ameliorates allergic inflammation by inhibiting key initiating factors in the initial stage of sensitization

    PubMed Central

    Bao, Kai-fan; Yu, Xi; Wei, Xiao; Gui, Li-li; Liu, Hai-liang; Wang, Xiao-yu; Tao, Yu; Jiang, Guo-rong; Hong, Min

    2016-01-01

    To illuminate the anti-allergy mechanism of astragaloside IV (AS-IV), we assessed its effects in a murine model of allergic contact dermatitis (ACD). AS-IV administered in the sensitization phase, rather than in the elicitation phase, dramatically alleviated the symptoms of allergic inflammation. We hypothesized that AS-IV exerts its anti-allergy effects by regulating the production of key pro-allergic cytokines based on the fact that interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) levels increase significantly in the initial stage of the sensitization phase. AS-IV administered in the initial stage of ACD inhibited TSLP and IL-33 expression and reduced the proportion of type-2 innate lymphoid cells (ILC2s). An in vitro study showed that the production of pro-allergic cytokines was significantly inhibited in AS-IV presenting HaCaT cells. We also verified that AS-IV administered only in the initial stage markedly alleviated inflammation, including ear swelling, Th2 cytokine expression, and histological changes. Taken together, these results suggest that AS-IV effectively ameliorates the progression of allergic inflammation by inhibiting key initiating factors, including TSLP and IL-33, and can be used to prevent and/or treat patients with ACD. Our data also suggest that these key pro-allergic cytokines are potential therapeutic targets for allergic diseases. PMID:27917896

  20. Three-Factor User Authentication and Key Agreement Using Elliptic Curve Cryptosystem in Wireless Sensor Networks

    PubMed Central

    Park, YoHan; Park, YoungHo

    2016-01-01

    Secure communication is a significant issue in wireless sensor networks. User authentication and key agreement are essential for providing a secure system, especially in user-oriented mobile services. It is also necessary to protect the identity of each individual in wireless environments to avoid personal privacy concerns. Many authentication and key agreement schemes utilize a smart card in addition to a password to support security functionalities. However, these schemes often fail to provide security along with privacy. In 2015, Chang et al. analyzed the security vulnerabilities of previous schemes and presented the two-factor authentication scheme that provided user privacy by using dynamic identities. However, when we cryptanalyzed Chang et al.’s scheme, we found that it does not provide sufficient security for wireless sensor networks and fails to provide accurate password updates. This paper proposes a security-enhanced authentication and key agreement scheme to overcome these security weaknesses using biometric information and an elliptic curve cryptosystem. We analyze the security of the proposed scheme against various attacks and check its viability in the mobile environment. PMID:27983616

  1. Three-Factor User Authentication and Key Agreement Using Elliptic Curve Cryptosystem in Wireless Sensor Networks.

    PubMed

    Park, YoHan; Park, YoungHo

    2016-12-14

    Secure communication is a significant issue in wireless sensor networks. User authentication and key agreement are essential for providing a secure system, especially in user-oriented mobile services. It is also necessary to protect the identity of each individual in wireless environments to avoid personal privacy concerns. Many authentication and key agreement schemes utilize a smart card in addition to a password to support security functionalities. However, these schemes often fail to provide security along with privacy. In 2015, Chang et al. analyzed the security vulnerabilities of previous schemes and presented the two-factor authentication scheme that provided user privacy by using dynamic identities. However, when we cryptanalyzed Chang et al.'s scheme, we found that it does not provide sufficient security for wireless sensor networks and fails to provide accurate password updates. This paper proposes a security-enhanced authentication and key agreement scheme to overcome these security weaknesses using biometric information and an elliptic curve cryptosystem. We analyze the security of the proposed scheme against various attacks and check its viability in the mobile environment.

  2. Effects of cell type and configuration on anabolic and catabolic activity in 3D co‐culture of mesenchymal stem cells and nucleus pulposus cells

    PubMed Central

    Ouyang, Ann; Cerchiari, Alec E.; Tang, Xinyan; Liebenberg, Ellen; Alliston, Tamara; Gartner, Zev J.

    2016-01-01

    ABSTRACT Tissue engineering constructs to treat intervertebral disc degeneration must adapt to the hypoxic and inflammatory degenerative disc microenvironment. The objective of this study was to determine the effects of two key design factors, cell type and cell configuration, on the regenerative potential of nucleus pulposus cell (NPC) and mesenchymal stem cell (MSC) constructs. Anabolic and catabolic activity was quantified in constructs of varying cell type (NPCs, MSCs, and a 50:50 co‐culture) and varying configuration (individual cells and micropellets). Anabolic and catabolic outcomes were both dependent on cell type. Gene expression of Agg and Col2A1, glycosaminoglycan (GAG) content, and aggrecan immunohistochemistry (IHC), were significantly higher in NPC‐only and co‐culture groups than in MSC‐only groups, with NPC‐only groups exhibiting the highest anabolic gene expression levels. However, NPC‐only constructs also responded to inflammation and hypoxia with significant upregulation of catabolic genes (MMP‐1, MMP‐9, MMP‐13, and ADAMTS‐5). MSC‐only groups were unaffected by degenerative media conditions, and co‐culture with MSCs modulated catabolic induction of the NPCs. Culturing cells in a micropellet configuration dramatically reduced catabolic induction in co‐culture and NPC‐only groups. Co‐culture micropellets, which take advantage of both cell type and configuration effects, had the most immunomodulatory response, with a significant decrease in MMP‐13 and ADAMTS‐5 expression in hypoxic and inflammatory media conditions. Co‐culture micropellets were also found to self‐organize into bilaminar formations with an MSC core and NPC outer layer. Further understanding of these cell type and configuration effects can improve tissue engineering designs. © 2016 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 35:61–73, 2017. PMID

  3. [Effect of anabolic steroid on immune response].

    PubMed

    Yamagishi, H; Kobayashi, M; Konosu, H; Kurioka, H; Naito, K; Sonoyama, T; Nishimoto, T; Hashimoto, I

    1984-03-01

    Using lymphocyte, monocyte and eosinophil counts of the peripheral blood, PHA-blastoid transformation, immunoglobulin and beta 2-microglobulin, the influence of anabolic steroid on the immune reactivity of the host was dissected by administration of Deca-Durabolin ( nandrolone decanoate) to both tumor-bearing host and tumor-free host after operation for alimentary tract. The number of peripheral lymphocytes and monocytes, the PHA-blastoid transformation of peripheral lymphocytes and the IgG level were increased, and the beta 2-microglobulin level showed the tendency of decrease after the administration of Deca-Durabolin.

  4. [Rhabdomyolysis in a bodybuilder using anabolic steroids].

    PubMed

    Hageloch, W; Appell, H J; Weicker, H

    1988-09-01

    The clinical course and the laboratory findings of a massive rhabdomyolysis in a male bodybuilder is presented. Particularly spectacular are the light- and electron-microscopical pictures of the histological findings. The acute renal failure as the most important and major life-threatening complication of the rhabdomyolysis is considered and the successful therapeutic procedure is described. The probability of a causal relation between anabolic steroids and rhabdomyolysis is discussed as well as the resulting consequences for the care of athletes in sports medicine.

  5. Acute myocardial infarction in a young man using anabolic steroids.

    PubMed

    Wysoczanski, Mariusz; Rachko, Maurice; Bergmann, Steven R

    2008-01-01

    Anabolic-androgenic steroids are used worldwide to help athletes gain muscle mass and strength. Their use and abuse is associated with numerous side effects, including acute myocardial infarction (MI). We report a case of MI in a young 31-year-old bodybuilder. Because of the serious cardiovascular complications of anabolic steroids, physicians should be aware of their abuse and consequences.

  6. Effect of demographics on excretion of key urinary factors related to kidney stone risk

    PubMed Central

    Perinpam, Majuran; Ware, Erin B.; Smith, Jennifer A.; Turner, Stephen T.; Kardia, Sharon L.R.; Lieske, John C.

    2015-01-01

    Objective To investigate the effect of demographics including age and sex on excretion of four key urinary factors (calcium (Ca), magnesium (Mg), oxalate (Ox) and uric acid (UA)) related to kidney stone risk. Methods Twenty-four hour urine samples were collected from non-Hispanic white sibships in Rochester, MN. Height, weight, blood pressure, serum creatinine and cystatin C (CC) were measured. Diet was assessed using the Viocare food frequency questionnaire. Effects of demographics and dietary elements on urinary excretions were evaluated in univariate, multivariate, and interaction models that included age, sex, and body mass index (BMI). Results Samples were available from 709 individuals. In multivariate models, sex was a significant predictor of all four urinary factors, age was significant for all but UA excretion, and serum creatinine was significant only for Ca and Mg excretion (p<0.05). BMI or weight positively correlated with Mg, Ox and UA excretion (p<0.05). Use of a thiazide diuretic (lower) and dietary protein (higher) were associated with Ca excretion, while dietary Ca was associated with higher Mg excretion. Urinary UA excretion increased with animal protein intake and CC estimated glomerular filtration rate (eGFR), and was lower with concurrent loop diuretic use. Significant interaction effects on urinary UA excretion were observed for loop diuretic use and sex, eGFR and sex, age and animal protein intake, and BMI and eGFR (p<0.05). Conclusions Age and sex influence excretion of key urinary factors related to kidney stone risk, and should be taken into account when evaluating kidney stone patients. PMID:26206452

  7. Key factor in rice husk ash/CaO sorbent for high flue gas desulfurization activity

    SciTech Connect

    Irvan Dahlan; Keat Teong Lee; Azlina Harun Kamaruddin; Abdul Rahman Mohamed

    2006-10-01

    Siliceous materials such as rice husk ash (RHA) have potential to be utilized as high performance sorbents for the flue gas desulfurization process in small-scale industrial boilers. This study presents findings on identifying the key factor for high desulfurization activity in sorbents prepared from RHA. Initially, a systematic approach using central composite rotatable design was used to develop a mathematical model that correlates the sorbent preparation variables to the desulfurization activity of the sorbent. The sorbent preparation variables studied are hydration period, x{sub 1} (6-16 h), amount of RHA, x{sub 2} (5-15 g), amount of CaO, x{sub 3} (2-6 g), amount of water, x{sub 4} (90-110 mL), and hydration temperature, x{sub 5} (150-250{sup o}C). The mathematical model developed was subjected to statistical tests and the model is adequate for predicting the SO{sub 2} desulfurization activity of the sorbent within the range of the sorbent preparation variables studied. Based on the model, the amount of RHA, amount of CaO, and hydration period used in the preparation step significantly influenced the desulfurization activity of the sorbent. The ratio of RHA and CaO used in the preparation mixture was also a significant factor that influenced the desulfurization activity of the sorbent. A RHA to CaO ratio of 2.5 leads to the formation of specific reactive species in the sorbent that are believed to be the key factor responsible for high desulfurization activity in the sorbent. Other physical properties of the sorbent such as pore size distribution and surface morphology were found to have insignificant influence on the desulfurization activity of the sorbent. 31 refs., 5 figs., 3 tabs.

  8. Fibroblast growth factor 2 is a key determinant of vascular sprouting during bovine luteal angiogenesis.

    PubMed

    Woad, Kathryn J; Hunter, Morag G; Mann, George E; Laird, Mhairi; Hammond, Amanda J; Robinson, Robert S

    2012-01-01

    Fibroblast growth factor (FGF) 2 and vascular endothelial growth factor (VEGF) A are thought to be key controllers of luteal angiogenesis; however, their precise roles in the regulation and coordination of this complex process remain unknown. Thus, the temporal and spatial patterns of endothelial network formation were determined by culturing mixed cell types from early bovine corpora lutea on fibronectin in the presence of FGF2 and VEGFA (6 h to 9 days). Endothelial cells, as determined by von Willebrand factor immunohistochemistry, initially grew in cell islands (days 0-3), before undergoing a period of vascular sprouting to display a more tubule-like appearance (days 3-6), and after 9 days in culture had formed extensive intricate networks. Mixed populations of luteal cells were treated with SU1498 (VEGF receptor 2 inhibitor) or SU5402 (FGF receptor 1 inhibitor) or control on days 0-3, 3-6 or 6-9 to determine the role of FGF2 and VEGFA during these specific windows. The total area of endothelial cells was unaffected by SU1498 treatment during any window. In contrast, SU5402 treatment caused maximal reduction in the total area of endothelial cell networks on days 3-6 vs controls (mean reduction 81%; P<0.001) during the period of tubule initiation. Moreover, SU5402 treatment on days 3-6 dramatically reduced the total number of branch points (P<0.001) and degree of branching per endothelial cell island (P<0.05) in the absence of changes in mean island area. This suggests that FGF2 is a key determinant of vascular sprouting and hence critical to luteal development.

  9. Identification of Key Contributory Factors Responsible for Vascular Dysfunction in Idiopathic Recurrent Spontaneous Miscarriage

    PubMed Central

    Dutta, Mainak; Subramani, Elavarasan; Khalpada, Jaydeep; RoyChoudhury, Sourav; Chakravarty, Baidyanath; Chaudhury, Koel

    2013-01-01

    Poor endometrial perfusion during implantation window is reported to be one of the possible causes of idiopathic recurrent spontaneous miscarriage (IRSM). We have tested the hypothesis that certain angiogenic and vasoactive factors are associated with vascular dysfunction during implantation window in IRSM and, therefore, could play a contributory role in making the endometrium unreceptive in these women. This is a prospective case-controlled study carried out on 66 women with IRSM and age and BMI matched 50 fertile women serving as controls. Endometrial expression of pro-inflammatory (IL-1β, TNF-α, IFN-γ, TGF-β1), anti-inflammatory (IL-4, -10), angiogenesis-associated cytokines (IL-2, -6, -8), angiogenic and vasoactive factors including prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), nitric oxide (NO) and adrenomedullin (ADM) were measured during implantation window by ELISA. Subendometrial blood flow (SEBF) was assessed by color Doppler ultrasonography. Multivariate analysis was used to identify the significant factor(s) responsible for vascular dysfunction in IRSM women during window of implantation and further correlated with vascular dysfunction. Endometrial expression of pro-inflammatory cytokines and PGE2 were up-regulated and anti-inflammatory and angiogenesis-associated cytokines down-regulated in IRSM women as compared with controls. Further, the angiogenic and vasoactive factors including VEGF, eNOS, NO and ADM were found to be down-regulated and SEBF grossly affected in these women. Multivariate analysis identified IL-10, followed by VEGF and eNOS as the major factors contributing towards vascular dysfunction in IRSM women. Moreover, these factors strongly correlated with blood flow impairment. This study provides an understanding that IL-10, VEGF and eNOS are the principal key components having a contributory role in endometrial vascular dysfunction in women with IRSM. Down-regulation of

  10. The Buzz About Anabolic Androgenic Steroids: Electrophysiological Effects in Excitable Tissues

    PubMed Central

    Oberlander, Joseph G.; Penatti, Carlos A. A.; Porter, Donna M.; Henderson, Leslie P.

    2012-01-01

    Anabolic androgenic steroids (AAS) comprise a large and growing class of synthetic androgens used clinically to promote tissue-building in individuals suffering from genetic disorders, injuries and diseases. Despite these beneficial therapeutic applications, the predominant use of AAS is illicit: these steroids are self-administered to promote athletic performance and body image. Hand in hand with the desired anabolic actions of the AAS are untoward effects on the brain and behavior. While the signaling routes by which the AAS impose both beneficial and harmful actions may be quite diverse, key endpoints are likely to include ligand-gated and voltage-dependent ion channels that govern the activity of electrically excitable tissues. Here we review the known effects of AAS on molecular targets that play critical roles in controlling electrical activity, with a specific focus on the effects of AAS on neurotransmission mediated by GABAA receptors in the central nervous system (CNS). PMID:22576754

  11. Mechanical signals as anabolic agents in bone.

    PubMed

    Ozcivici, Engin; Luu, Yen Kim; Adler, Ben; Qin, Yi-Xian; Rubin, Janet; Judex, Stefan; Rubin, Clinton T

    2010-01-01

    Aging and a sedentary lifestyle conspire to reduce bone quantity and quality, decrease muscle mass and strength, and undermine postural stability, culminating in an elevated risk of skeletal fracture. Concurrently, a marked reduction in the available bone-marrow-derived population of mesenchymal stem cells (MSCs) jeopardizes the regenerative potential that is critical to recovery from musculoskeletal injury and disease. A potential way to combat the deterioration involves harnessing the sensitivity of bone to mechanical signals, which is crucial in defining, maintaining and recovering bone mass. To effectively utilize mechanical signals in the clinic as a non-drug-based intervention for osteoporosis, it is essential to identify the components of the mechanical challenge that are critical to the anabolic process. Large, intense challenges to the skeleton are generally presumed to be the most osteogenic, but brief exposure to mechanical signals of high frequency and extremely low intensity, several orders of magnitude below those that arise during strenuous activity, have been shown to provide a significant anabolic stimulus to bone. Along with positively influencing osteoblast and osteocyte activity, these low-magnitude mechanical signals bias MSC differentiation towards osteoblastogenesis and away from adipogenesis. Mechanical targeting of the bone marrow stem-cell pool might, therefore, represent a novel, drug-free means of slowing the age-related decline of the musculoskeletal system.

  12. Mechanical signals as anabolic agents in bone

    PubMed Central

    Ozcivici, Engin; Luu, Yen Kim; Adler, Ben; Qin, Yi-Xian; Rubin, Janet; Judex, Stefan; Rubin, Clinton T.

    2013-01-01

    Aging and a sedentary lifestyle conspire to reduce bone quantity and quality, decrease muscle mass and strength, and undermine postural stability, culminating in an elevated risk of skeletal fracture. Concurrently, a marked reduction in the available bone-marrow-derived population of mesenchymal stem cells (MSCs) jeopardizes the regenerative potential that is critical to recovery from musculoskeletal injury and disease. A potential way to combat the deterioration involves harnessing the sensitivity of bone to mechanical signals, which is crucial in defining, maintaining and recovering bone mass. To effectively utilize mechanical signals in the clinic as a non-drug-based intervention for osteoporosis, it is essential to identify the components of the mechanical challenge that are critical to the anabolic process. Large, intense challenges to the skeleton are generally presumed to be the most osteogenic, but brief exposure to mechanical signals of high frequency and extremely low intensity, several orders of magnitude below those that arise during strenuous activity, have been shown to provide a significant anabolic stimulus to bone. Along with positively influencing osteoblast and osteocyte activity, these low-magnitude mechanical signals bias MSC differentiation towards osteoblastogenesis and away from adipogenesis. Mechanical targeting of the bone marrow stem-cell pool might, therefore, represent a novel, drug-free means of slowing the age-related decline of the musculoskeletal system. PMID:20046206

  13. Transcription Factor RFX2 Is a Key Regulator of Mouse Spermiogenesis

    PubMed Central

    Wu, Yujian; Hu, Xiangjing; Li, Zhen; Wang, Min; Li, Sisi; Wang, Xiuxia; Lin, Xiwen; Liao, Shangying; Zhang, Zhuqiang; Feng, Xue; Wang, Si; Cui, Xiuhong; Wang, Yanling; Gao, Fei; Hess, Rex A.; Han, Chunsheng

    2016-01-01

    The regulatory factor X (RFX) family of transcription factors is crucial for ciliogenesis throughout evolution. In mice, Rfx1-4 are highly expressed in the testis where flagellated sperm are produced, but the functions of these factors in spermatogenesis remain unknown. Here, we report the production and characterization of the Rfx2 knockout mice. The male knockout mice were sterile due to the arrest of spermatogenesis at an early round spermatid step. The Rfx2-null round spermatids detached from the seminiferous tubules, forming large multinucleated giant cells that underwent apoptosis. In the mutants, formation of the flagellum was inhibited at its earliest stage. RNA-seq analysis identified a large number of cilia-related genes and testis-specific genes that were regulated by RFX2. Many of these genes were direct targets of RFX2, as revealed by chromatin immunoprecipitation-PCR assays. These findings indicate that RFX2 is a key regulator of the post-meiotic development of mouse spermatogenic cells. PMID:26853561

  14. The plant RWP-RK transcription factors: key regulators of nitrogen responses and of gametophyte development.

    PubMed

    Chardin, Camille; Girin, Thomas; Roudier, François; Meyer, Christian; Krapp, Anne

    2014-10-01

    The plant specific RWP-RK family of transcription factors, initially identified in legumes and Chlamydomonas, are found in all vascular plants, green algae, and slime molds. These proteins possess a characteristic RWP-RK motif, which mediates DNA binding. Based on phylogenetic and domain analyses, we classified the RWP-RK proteins of six different species in two subfamilies: the NIN-like proteins (NLPs), which carry an additional PB1 domain at their C-terminus, and the RWP-RK domain proteins (RKDs), which are divided into three subgroups. Although, the functional analysis of this family is still in its infancy, several RWP-RK proteins have a key role in regulating responses to nitrogen availability. The nodulation-specific NIN proteins are involved in nodule organogenesis and rhizobial infection under nitrogen starvation conditions. Arabidopsis NLP7 in particular is a major player in the primary nitrate response. Several RKDs act as transcription factors involved in egg cell specification and differentiation or gametogenesis in algae, the latter modulated by nitrogen availability. Further studies are required to extend the general picture of the functional role of these exciting transcription factors.

  15. Identification of guanine exchange factor key residues involved in exchange activity and Ras interaction.

    PubMed

    Camus, C; Hermann-Le Denmat, S; Jacquet, M

    1995-09-07

    We have carried out a functional analysis of the human HGRF55 exchange factor in the yeast Saccharomyces cerevisiae. Twelve residues conserved among most of all known guanine exchange factors (GEFs) have been independently changed to alanine. Taking advantage of the ability of Hgrf55p to replace the yeast Cdc25p exchange factor, and using the two-hybrid system with RAS2ala22 allele, we have identified key residues for the interaction with Ras and/or its activation. Substitution of arginine 392 to alanine leads to a complete loss of interaction with Ras, though the protein remains stable. Substitution of Asp266 or Arg359 to alanine results in inactive proteins at 39 degrees C, still able however to interact with Ras. The other charged-to-alanine substitutions led to no detectable phenotype when present alone but most of them dramatically increased the temperature sensitive phenotype observed with [Asp266Ala] substitution. Surprisingly, the cysteine to alanine substitution in the highly conserved PCVPF/Y motif proved to be without effect, suggesting that the sulfhydryl group is not essential for stability or interaction with Ras.

  16. Key factors of eddy current separation for recovering aluminum from crushed e-waste.

    PubMed

    Ruan, Jujun; Dong, Lipeng; Zheng, Jie; Zhang, Tao; Huang, Mingzhi; Xu, Zhenming

    2017-02-01

    Recovery of e-waste in China had caused serious pollutions. Eddy current separation is an environment-friendly technology of separating nonferrous metallic particles from crushed e-waste. However, due to complex particle characters, separation efficiency of traditional eddy current separator was low. In production, controllable operation factors of eddy current separation are feeding speed, (ωR-v), and Sp. There is little special information about influencing mechanism and critical parameters of these factors in eddy current separation. This paper provided the special information of these key factors in eddy current separation of recovering aluminum particles from crushed waste refrigerator cabinets. Detachment angles increased as the increase of (ωR-v). Separation efficiency increased with the growing of detachment angles. Aluminum particles were completely separated from plastic particles in critical parameters of feeding speed 0.5m/s and detachment angles greater than 6.61deg. Sp/Sm of aluminum particles in crushed waste refrigerators ranged from 0.08 to 0.51. Separation efficiency increased as the increase of Sp/Sm. This enlightened us to develop new separator to separate smaller nonferrous metallic particles in e-waste recovery. High feeding speed destroyed separation efficiency. However, greater Sp of aluminum particles brought positive impact on separation efficiency. Greater Sp could increase critical feeding speed to offer greater throughput of eddy current separation. This paper will guide eddy current separation in production of recovering nonferrous metals from crushed e-waste.

  17. Adjuvants are Key Factors for the Development of Future Vaccines: Lessons from the Finlay Adjuvant Platform

    PubMed Central

    Pérez, Oliver; Romeu, Belkis; Cabrera, Osmir; González, Elizabeth; Batista-Duharte, Alexander; Labrada, Alexis; Pérez, Rocmira; Reyes, Laura M.; Ramírez, Wendy; Sifontes, Sergio; Fernández, Nelson; Lastre, Miriam

    2013-01-01

    The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs), AFPL (proteoliposome), and AFCo (cochleate), were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed. PMID:24348475

  18. Key factors influencing rates of heterotrophic sulfate reduction in hydrothermal massive sulfide deposits

    NASA Astrophysics Data System (ADS)

    Frank, K. L.; Rogers, D.; Girguis, P. R.

    2012-12-01

    Despite sulfate reduction's ubiquity in marine systems, relatively little is known about how environmental or ecological factors influence rates of sulfate reduction. While numerous studies have considered how sulfate reduction and methanogenesis compete for reductants in natural and human-made systems, less is known about how temperature or metabolite concentration, such as sulfate and sulfide concentrations, affects rates of sulfate reduction. Here we use a factorial experimental design to evaluate the effects of key variables on sulfate reduction kinetics in sulfide deposits recovered from hydrothermal vents in the Main Endeavor Field, Juan de Fuca ridge. Microbial sulfate reduction rates were measured by 35-S tracer techniques over a range of environmentally relevant chemical conditions (pH, H2S, SO42-, and organic carbon concentrations) and temperatures (4, 50 and 90°C). Maximum sulfate reduction rates were observed at 50°C, and sulfate reduction rates had significant positive correlations with increasing sulfide, pH and sulfate. However, sulfate reduction rates did not correlate to exogenous dissolved organic carbon, implicating exogenous hydrogen or endogenous organic matter as the reductant (or even sulfur disproportionation). This research presents an opportunity to better understand the key variables that influence the rates of microbial sulfate reduction in hydrothermal environments and provides a framework for modeling sulfate reduction in mid-ocean ridge systems.

  19. Adjuvants are Key Factors for the Development of Future Vaccines: Lessons from the Finlay Adjuvant Platform.

    PubMed

    Pérez, Oliver; Romeu, Belkis; Cabrera, Osmir; González, Elizabeth; Batista-Duharte, Alexander; Labrada, Alexis; Pérez, Rocmira; Reyes, Laura M; Ramírez, Wendy; Sifontes, Sergio; Fernández, Nelson; Lastre, Miriam

    2013-12-02

    The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs), AFPL (proteoliposome), and AFCo (cochleate), were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed.

  20. A Secure Three-Factor User Authentication and Key Agreement Protocol for TMIS With User Anonymity.

    PubMed

    Amin, Ruhul; Biswas, G P

    2015-08-01

    Telecare medical information system (TMIS) makes an efficient and convenient connection between patient(s)/user(s) and doctor(s) over the insecure internet. Therefore, data security, privacy and user authentication are enormously important for accessing important medical data over insecure communication. Recently, many user authentication protocols for TMIS have been proposed in the literature and it has been observed that most of the protocols cannot achieve complete security requirements. In this paper, we have scrutinized two (Mishra et al., Xu et al.) remote user authentication protocols using smart card and explained that both the protocols are suffering against several security weaknesses. We have then presented three-factor user authentication and key agreement protocol usable for TMIS, which fix the security pitfalls of the above mentioned schemes. The informal cryptanalysis makes certain that the proposed protocol provides well security protection on the relevant security attacks. Furthermore, the simulator AVISPA tool confirms that the protocol is secure against active and passive attacks including replay and man-in-the-middle attacks. The security functionalities and performance comparison analysis confirm that our protocol not only provide strong protection on security attacks, but it also achieves better complexities along with efficient login and password change phase as well as session key verification property.

  1. Hepatocyte growth factor plays a key role in insulin resistance-associated compensatory mechanisms.

    PubMed

    Araújo, Tiago G; Oliveira, Alexandre G; Carvalho, Bruno M; Guadagnini, Dioze; Protzek, André O P; Carvalheira, Jose B C; Boschero, Antonio C; Saad, Mario J A

    2012-12-01

    Insulin resistance is present in obesity and in type 2 diabetes and is associated with islet cell hyperplasia and hyperinsulinemia, but the driving forces behind this compensatory mechanism are incompletely understood. Previous data have suggested the involvement of an unknown circulating insulin resistance-related β-cell growth factor. In this context, looking for candidates to be a circulating factor, we realized that hepatocyte growth factor (HGF) is a strong candidate as a link between insulin resistance and increased mass of islets/hyperinsulinemia. Our approach aimed to show a possible cause-effect relationship between increase in circulating HGF levels and compensatory islet hyperplasia/hyperinsulinemia by showing the strength of the association, whether or not is a dose-dependent response, the temporality, consistency, plausibility, and reversibility of the association. In this regard, our data showed: 1) a strong and consistent correlation between HGF and the compensatory mechanism in three animal models of insulin resistance; 2) HGF increases β-cell mass in a dose-dependent manner; 3) blocking HGF shuts down the compensatory mechanisms; and 4) an increase in HGF levels seems to precede the compensatory response associated with insulin resistance, indicating that these events occur in a sequential mode. Additionally, blockages of HGF receptor (Met) worsen the impaired insulin-induced insulin signaling in liver of diet-induced obesity rats. Overall, our data indicate that HGF is a growth factor playing a key role in islet mass increase and hyperinsulinemia in diet-induced obesity rats and suggest that the HGF-Met axis may have a role on insulin signaling in the liver.

  2. Expression profiles of key transcription factors involved in lipid metabolism in Beijing-You chickens.

    PubMed

    Fu, R Q; Liu, R R; Zhao, G P; Zheng, M Q; Chen, J L; Wen, J

    2014-03-01

    Intramuscular fat (IMF) is a crucial factor for the meat quality of chickens. With the aim of studying the molecular mechanisms underlying IMF deposition in chickens, the expression profiles of five candidate transcription factors involved in lipid metabolism in several tissues were examined in Beijing-You (BJY) chickens at five ages (0, 4, 8, 14 and 20 wk). Results showed that accumulation of IMF in breast (IMFbr), thigh (IMFth) and abdominal fat weight increased significantly (P<0.01) after 8 wk. Accumulation of both IMFbr and IMFth from 8 to 14 wk exceeded that from 14 to 20 wk; IMFth was 4-7 times of IMFbr. As for the expression profiles of key transcription factors: 1) expression of C/EBPα and PPARγ in abdominal fat was significantly higher than that in breast and thigh muscles at all ages. The expression of C/EBPα was positively correlated with PPARγ in both breast and thigh muscles, which indicated that both C/EBPα and PPARγ promoted fat deposition and might act through a unified pathway; 2) the expression of SREBP-1 in 0, 4, and 8 wk in thigh muscle was significantly higher than that in breast; 3) expression of C/EBPβ at 4 and 8 wk was significantly higher than that at 14 and 20 wk; and it was positively correlated with IMFth and IMFbr from 0 to 8 wk; 4) expression of PPARα in breast and thigh muscles was significantly higher than that in abdominal fat. Taken together, all five transcription factors studied play roles in lipid metabolism in chickens with C/EBPα and PPARγ being important effectors.

  3. Tissue Factor–Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes

    PubMed Central

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF–fVII complex. Here, we discuss the roles of the TF–fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF–fVII function. PMID:26396550

  4. Prevalence of Anabolic Steroid Use Among Illinois High School Students

    PubMed Central

    Tuttle, Leslye D.; Gaa, Gregory L.; Griffith, Edwin H.; Cahill, Bernard R.

    1994-01-01

    This study was conducted to quantify anabolic steroid use in Illinois, investigate student knowledge and perception of anabolic steroid use, and identify characteristics of the anabolic steroid user. We surveyed 3047 freshman and senior high school students from 38 high schools, randomly selected from three school enrollment sizes and five geographic locations, using a six-page anonymous questionnaire. Anabolic steroid use was reported by 58 (1.9%) of the participants, 44 of 1477 (3%) males and 14 of 1562 (0.9%) females. Thirty-four of 1679 (2%) freshman and 24 of 1366 (1.8%) seniors reported use. Anabolic steroids were used in all possible school enrollment sizes and geographic locations (matrix cells). Four (7%) of the users reported starting at age 10 or younger. A teacher/coach was reported as a primary source by 8 (14%) of the users, as well as identified by 11 (19%) of the users as the individual they knew using anabolic steroids. It appears that anabolic steroids are being introduced to students in elementary and junior high schools, and that teachers/coaches are actively involved in their use. PMID:16558283

  5. 21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are...

  6. 21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are...

  7. 21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are...

  8. 21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are...

  9. 21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are...

  10. Distributions of key exposure factors controlling the uptake of xenobiotic chemicals in an estuarine food web

    SciTech Connect

    Iannuzzi, T.J.; Harrington, N.W.; Shear, N.M.; Curry, C.L.; Carlson-Lynch, H.; Henning, M.H.; Su, S.H.; Rabbe, D.E.

    1996-11-01

    A critical evaluation of literature on the behavior, physiology, and ecology of common estuarine organisms was conducted in an attempt to develop probabilistic distributions for those variables that influence the uptake of xenobiotic chemicals from sediments, water, and food sources. The ranges, central tendencies, and distributions of several key parameter values were identified for dominant organisms from various trophic levels, including the polychaete Nereis virens, mummichog (Fundulus heteroclitus), blue crab (Callinectes sapidus), and striped bass (Morone saxatilis). The exposure factors of interest included ingestion rate for various food sources, growth rate, respiration rate, excretion rate, body weight, wet/dry weight ratio, lipid content, chemical assimilation efficiency, and food assimilation efficiency. These exposure factors are critical to the execution of mechanistic food web models, which, when properly calibrated, can be used to estimate tissue concentrations of nonionic chemicals in aquatic organisms based on knowledge of the bioenergetics and feeding interactions within a food web and the sediment and water concentrations of chemicals. In this article the authors describe the use of distributions for various exposure factors in the context of a mechanistic bioaccumulation model that is amenable to probabilistic analyses for multiple organisms within a food web. A case study is provided which compares the estimated versus measured concentrations of five polychlorinated biphenyl (PCB) congeners in a representative food web from the tidal portion of the Passaic River, New Jersey, USA. The results suggest that the model is accurate within an order of magnitude or less in estimating the bioaccumulation of PCBs in this food web without calibration. The results of a model sensitivity analysis suggest that the input parameters which most influence the output of the model are both chemical and organism specific.

  11. Effects of androgenic-anabolic steroids in athletes.

    PubMed

    Hartgens, Fred; Kuipers, Harm

    2004-01-01

    Androgenic-anabolic steroids (AAS) are synthetic derivatives of the male hormone testosterone. They can exert strong effects on the human body that may be beneficial for athletic performance. A review of the literature revealed that most laboratory studies did not investigate the actual doses of AAS currently abused in the field. Therefore, those studies may not reflect the actual (adverse) effects of steroids. The available scientific literature describes that short-term administration of these drugs by athletes can increase strength and bodyweight. Strength gains of about 5-20% of the initial strength and increments of 2-5 kg bodyweight, that may be attributed to an increase of the lean body mass, have been observed. A reduction of fat mass does not seem to occur. Although AAS administration may affect erythropoiesis and blood haemoglobin concentrations, no effect on endurance performance was observed. Little data about the effects of AAS on metabolic responses during exercise training and recovery are available and, therefore, do not allow firm conclusions. The main untoward effects of short- and long-term AAS abuse that male athletes most often self-report are an increase in sexual drive, the occurrence of acne vulgaris, increased body hair and increment of aggressive behaviour. AAS administration will disturb the regular endogenous production of testosterone and gonadotrophins that may persist for months after drug withdrawal. Cardiovascular risk factors may undergo deleterious alterations, including elevation of blood pressure and depression of serum high-density lipoprotein (HDL)-, HDL2- and HDL3-cholesterol levels. In echocardiographic studies in male athletes, AAS did not seem to affect cardiac structure and function, although in animal studies these drugs have been observed to exert hazardous effects on heart structure and function. In studies of athletes, AAS were not found to damage the liver. Psyche and behaviour seem to be strongly affected by AAS

  12. Myocardial ischemia is a key factor in the management of stable coronary artery disease

    PubMed Central

    Iwasaki, Kohichiro

    2014-01-01

    Previous studies demonstrated that coronary revascularization, especially percutaneous coronary intervention (PCI), does not significantly decrease the incidence of cardiac death or myocardial infarction in patients with stable coronary artery disease. Many studies using myocardial perfusion imaging (MPI) showed that, for patients with moderate to severe ischemia, revascularization is the preferred therapy for survival benefit, whereas for patients with no to mild ischemia, medical therapy is the main choice, and revascularization is associated with increased mortality. There is some evidence that revascularization in patients with no or mild ischemia is likely to result in worsened ischemia, which is associated with increased mortality. Studies using fractional flow reserve (FFR) demonstrate that ischemia-guided PCI is superior to angiography-guided PCI, and the presence of ischemia is the key to decision-making for PCI. Complementary use of noninvasive MPI and invasive FFR would be important to compensate for each method’s limitations. Recent studies of appropriateness criteria showed that, although PCI in the acute setting and coronary bypass surgery are properly performed in most patients, PCI in the non-acute setting is often inappropriate, and stress testing to identify myocardial ischemia is performed in less than half of patients. Also, some studies suggested that revascularization in an inappropriate setting is not associated with improved prognosis. Taken together, the presence and the extent of myocardial ischemia is a key factor in the management of patients with stable coronary artery disease, and coronary revascularization in the absence of myocardial ischemia is associated with worsened prognosis. PMID:24772253

  13. Anabolic actions of Notch on mature bone

    PubMed Central

    Liu, Peng; Ping, Yilin; Ma, Meng; Zhang, Demao; Liu, Connie; Zaidi, Samir; Gao, Song; Ji, Yaoting; Lou, Feng; Yu, Fanyuan; Lu, Ping; Stachnik, Agnes; Bai, Mingru; Wei, Chengguo; Zhang, Liaoran; Wang, Ke; Chen, Rong; New, Maria I.; Rowe, David W.; Yuen, Tony; Sun, Li; Zaidi, Mone

    2016-01-01

    Notch controls skeletogenesis, but its role in the remodeling of adult bone remains conflicting. In mature mice, the skeleton can become osteopenic or osteosclerotic depending on the time point at which Notch is activated or inactivated. Using adult EGFP reporter mice, we find that Notch expression is localized to osteocytes embedded within bone matrix. Conditional activation of Notch signaling in osteocytes triggers profound bone formation, mainly due to increased mineralization, which rescues both age-associated and ovariectomy-induced bone loss and promotes bone healing following osteotomy. In parallel, mice rendered haploinsufficient in γ-secretase presenilin-1 (Psen1), which inhibits downstream Notch activation, display almost-absent terminal osteoblast differentiation. Consistent with this finding, pharmacologic or genetic disruption of Notch or its ligand Jagged1 inhibits mineralization. We suggest that stimulation of Notch signaling in osteocytes initiates a profound, therapeutically relevant, anabolic response. PMID:27036007

  14. [Control measures for anabolic androgenic steroid medicines].

    PubMed

    Vázquez-Mourelle, Raquel; Carracedo-Martínez, Eduardo; Ces Gens, Eugenio; Cadórniga Valiño, Luis; Álvaro Esteban, Pilar; Pose Reino, José Manuel

    2015-01-01

    Anabolic androgenic steroids (AAS) can cause serious adverse effects when used without a therapeutic purpose. This article aims to show that the AAS are susceptible to being sold on the black market. We also aim to describe how certain limitations on the health inspection services of the Galician health service to pursue these illegal actions prompted a regulatory initiative demanding that additional actions be granted to community pharmacies when dispensing AAS. Four pharmacy inspections detected the diversion of a total of 3118 packages of AAS, which led to the opening of four disciplinary proceedings. In two of these, specialized police forces were called in as there was sufficient evidence of possible diversion to gymnasiums, resulting in a police operation called Operation Fitness.

  15. [Research progresses of anabolic steroids analysis in doping control].

    PubMed

    Long, Yuanyuan; Wang, Dingzhong; Li, Ke'an; Liu, Feng

    2008-07-01

    Anabolic steroids, a kind of physiological active substance, are widely abused to improve athletic performance in human sports. They have been forbidden in sports by the International Olympic Committee since 1983. Since then, many researchers have been focusing their attentions on the establishment of reliable detection methods. In this paper, we review the research progresses of different analytical methods for anabolic steroids since 2002, such as gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, immunoassay, electrochemistry analysis and mass spectrometry. The developing prospect of anabolic steroids analysis is also discussed.

  16. Hepatocellular carcinoma associated with recreational anabolic steroid use.

    PubMed

    Gorayski, P; Thompson, C H; Subhash, H S; Thomas, A C

    2008-01-01

    A 35-year-old male bodybuilder was found to have a hepatocellular carcinoma (HCC) arising in a pre-existing hepatic adenoma following recreational anabolic steroid use. Given the widespread use of recreational anabolic steroids, another potentially life-threatening complication is highlighted in addition to the more commonly recognised hepatic adenoma. Malignant transformation to HCC from a pre-existing hepatic adenoma confirmed by immunohistochemical study has previously not been reported in athletes taking anabolic steroids. Further studies using screening programmes to identify high-risk individuals are recommended.

  17. Wernicke's encephalopathy and anabolic steroid drug abuse. Is there any possible relation?

    PubMed Central

    Christopoulos, P; Katsanoulas, C; Timplalexi, G; Lathyris, D; Vasiliagkou, S; Antoniadou, E

    2012-01-01

    Wernicke's encephalopathy is a reversible, neurologic disorder due to thiamine deficiency which is mainly related to chronic alcohol abuse. We report a case of a young male patient, who was bodybuilder and anabolic drug user, in whom encephalopathy was diagnosed after a short medical course in the ICU after a major upper gastrointestinal bleeding (Mallory-Weiss syndrome) and hypovolemic shock. His clinical condition was typical for Wernicke's encephalopathy and although neuroimaging tests were not indicative, the patient received thiamine supplement therapy, which resulted in rapid clinical improvement. The diagnosis was based only on clinical sings and anabolic drug abuse was considered as a possible predisposing factor for the manifestation of the syndrome. PMID:23935320

  18. Multiple Intussusceptions Associated with Polycythemia in an Anabolic Steroid Abuser, A Case Report and Literature Review.

    PubMed

    Cavanagh, Y; Shah, N; Thomas, A B; Gupta, A

    2015-01-01

    Intussusceptions are generally associated with mechanical lead points or localized inflammation that function as foci for intestinal telescoping. We present the case of a patient whose abuse of anabolic steroids resulted in the development of multiple simultaneous intussusceptions. Our patient had no additional identifiable risk factors for intussusception. Consistent with previous reports, corticosteroid induced polycythemia and its consequent hyperviscosity led to intravascular sludging and mesenteric ischemia with associated bowel wall thickening. The localized intestinal induration then served as mechanical foci for intussusception. Due to the illicit nature of anabolic androgenic steroid (AAS) abuse, the physiologic effects of supraphysiologic doses are sparsely reported and poorly understood. The scope of AAS abuse and its consequences are likely under-reported and under-recognized within the medical community. Our case presented a unique diagnostic and therapeutic challenge with which we aim to increasing awareness and clinical suspicion for AAS among healthcare personnel.

  19. Modeling and analysis of PM2.5 generation for key factors identification in China

    NASA Astrophysics Data System (ADS)

    Xia, Dehong; Jiang, Binfan; Xie, Yulei

    2016-06-01

    Recently, the PM2.5 pollution in China has occurred frequently and caused widely concern. In order to identify the key factors for PM2.5 generation, the formation characteristics of PM2.5 would be revealed. A property of electric neutrality of PM2.5 was proposed under the least-energy principle and verified through electricity-charge calculation in this paper. It indicated that PM2.5 is formed by the effect of electromagnetic force, including the effect of ionic bond, hydrogen bond and polarization. According to the analysis of interactive forces among different chemical components, a simulation model is developed for describing the random process of PM2.5 generation. In addition, an orthogonal test with two levels and four factors has been designed and carried out through the proposed model. From the text analysis, PM2.5 would be looser and suspend longer in atmosphere due to Organic Compound (OC) existing (OC can reduce about 67% of PM2.5 density). Considering that NH4+ is the only cation in the main chemical components of PM2.5, it would be vital for anions (such as SO42- and NO3-) to aggregate together for facilitating PM2.5 growing. Therefore, in order to relieve PM2.5 pollution, control strategies for OC and NH4+ would be enhanced by government through improving the quality of oils and solvent products, decreasing the amount of nitrogenous fertilizer utilization, or changing the fertilizing environment from dry condition to wet condition.

  20. Gremlin is a Key Pro-fibrogenic Factor in Chronic Pancreatitis

    PubMed Central

    Xu, Meihua; Feng, Xueping; Aronson, Judith F.; Falzon, Miriam; Greeley, George H.; Rastellini, Cristiana; Chao, Celia; Hellmich, Mark R.; Cao, Yanna; Ko, Tien C.

    2016-01-01

    The current study aims to identify the pro-fibrogenic role of Gremlin, an endogenous antagonist of bone morphogenetic proteins (BMPs) in chronic pancreatitis (CP). CP is a highly debilitating disease characterized by progressive pancreatic inflammation and fibrosis that ultimately leads to exocrine and endocrine dysfunction. While transforming growth factor (TGF)-β is a known key pro-fibrogenic factor in CP, the TGF-β superfamily members BMPs exert an anti-fibrogenic function in CP reported by our group recently. To investigate how BMP signaling is regulated in CP by BMP antagonists, the mouse CP model induced by cerulein was used. During CP induction, TGF-β1 mRNA increased 156-fold in two weeks, a BMP antagonist Gremlin 1 (Grem1) mRNA levels increased 145-fold at three weeks, and increases in Grem1 protein levels correlated with increases in collagen deposition. Increased Grem1 was also observed in human CP pancreata compared to normal. Grem1 knockout in Grem1+/− mice revealed a 33.2% reduction in pancreatic fibrosis in CP compared to wild-type littermates. In vitro in isolated pancreatic stellate cells, TGF-β induced Grem1 expression. Addition of the recombinant mouse Grem1 protein blocked BMP2-induced Smad1/5 phosphorylation and abolished BMP2's suppression effects on TGF-β-induced collagen expression. Evidences presented herein demonstrate that Grem1, induced by TGF-β, is pro-fibrogenic by antagonizing BMP activity in CP. PMID:26141517

  1. Human Factors Engineering Program Review Model (NUREG-0711)Revision 3: Update Methodology and Key Revisions

    SciTech Connect

    OHara J. M.; Higgins, J.; Fleger, S.

    2012-07-22

    The U.S. Nuclear Regulatory Commission (NRC) reviews the human factors engineering (HFE) programs of applicants for nuclear power plant construction permits, operating licenses, standard design certifications, and combined operating licenses. The purpose of these safety reviews is to help ensure that personnel performance and reliability are appropriately supported. Detailed design review procedures and guidance for the evaluations is provided in three key documents: the Standard Review Plan (NUREG-0800), the HFE Program Review Model (NUREG-0711), and the Human-System Interface Design Review Guidelines (NUREG-0700). These documents were last revised in 2007, 2004 and 2002, respectively. The NRC is committed to the periodic update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool. To this end, the NRC is updating its guidance to stay current with recent research on human performance, advances in HFE methods and tools, and new technology being employed in plant and control room design. NUREG-0711 is the first document to be addressed. We present the methodology used to update NUREG-0711 and summarize the main changes made. Finally, we discuss the current status of the update program and the future plans.

  2. Inactivation of key factors of the plasma proteinase cascade systems by Bacteroides gingivalis.

    PubMed Central

    Nilsson, T; Carlsson, J; Sundqvist, G

    1985-01-01

    The effect of Bacteroides gingivalis W83 on various key components of the human plasma proteinase cascade systems was studied. When purified C1-inhibitor was incubated with the bacterium, the inhibitor was rapidly inactivated by limited proteolytic cleavage. In citrated whole plasma, C1-inhibitor, antithrombin, plasminogen, prekallikrein, prothrombinase complex, the clotting factor X, and most of the alpha 2-antiplasmin were functionally eliminated after 30 min of incubation with the bacterium. Fibrinogen disappeared from the plasma almost immediately upon mixing with the bacterial suspension. In contrast, there was no appreciable decrease in the bulk of other plasma proteins, such as various transport proteins (albumin, prealbumin, transferrin) and immunoglobulins, during 4 h of incubation with the bacterium. Most of the observed effects can be assigned to the proteolytic activity of the bacterium itself, since there was little evidence for generation of intrinsic plasma proteinase activity, despite the loss of proteinase inhibitory activities. B. gingivalis W83 thus seems to be equipped with proteolytic enzyme systems which selectively recognize and rapidly inactivate the most important proteinase inhibitors and proenzymes present in human plasma. This bacterium therefore seems to be able to efficiently paralyze the host's various defenses against invading microorganisms. Images PMID:3902645

  3. Key factors determining the efficacy of gene therapy for continuous DOPA delivery in the Parkinsonian brain.

    PubMed

    Cederfjäll, Erik; Sahin, Gurdal; Kirik, Deniz

    2012-11-01

    L-DOPA is currently the standard treatment for alleviating the motor symptoms in Parkinson's disease. The therapeutic efficacy, however, diminishes as the disease progresses. It has been suggested that the beneficial effect of L-DOPA could be reestablished by changing the mode of administration. Indeed, continuous delivery of l-DOPA has been shown to be an effective way to circumvent many of the side effects seen with traditional oral administration, which results in an intermittent supply of the dopamine precursor to the brain. However, all currently tested continuous dopaminergic stimulation approaches rely on peripheral administration. This is not ideal since it gives rise to off target effects and is difficult to maintain long-term. Thus, there is an unmet need for an effective continuous administration method with an acceptable side effect profile. Viral-mediated gene therapy is a promising alternative paradigm that can meet this demand. Encouraging preclinical studies in animal models of Parkinson's disease showed therapeutic efficacy after expression of the genes encoding the enzymes required for biosynthesis of dopamine. Although the first phase I clinical trials using these approaches have been conducted, clear positive data in placebo controlled efficacy studies is still lacking. We are now at a critical junction and need to carefully review the preclinical data from the clinical translation perspective and identify the key factors that will determine the potential for success in gene therapy for Parkinson's disease.

  4. Components of breeding productivity in a marine bird community: key factors and concordance

    USGS Publications Warehouse

    Hatch, Scott A.; Hatch, Martha A.

    1990-01-01

    We estimated components of annual breeding productivity for eight species of marine birds on the Semidi Islands in the western Gulf of Alaska. Mortality of eggs and young, caused primarily by avian predators, accounted for most of the annual variation in productivity. Failure to produce eggs, clutch size variation, and the hatchability of eggs were generally less important. The stage of breeding at which annual productivity was most strongly regulated differed among species. In murres, chick-rearing success accounted for the largest share of annual variation in overall productivity, whereas incubation success was the key factor in fulmars, kittiwakes, and puffins. Although avian predators were the dominant proximate cause of egg and chick losses in some species, food supply seemed ultimately responsible for variation in all the major components of productivity. Concordance of productivity among species was low for the marine bird community as a whole, but selected pairs of species exhibited a greater tendency for high and low productivities to occur in the same years. Compared with the same or similar species outside Alaska, Semidi Islands birds were in one of three categories: (i) species whose productivity was about the same as reported from other areas (fulmars and gulls), (ii) species with comparatively low productivity (murres, puffins, kittiwakes), and (iii) species with similar mean productivity but greater annual variation (cormorants). These patterns suggest that specialized consumers of forage fish experienced food shortages at the Semidi Islands and that surface feeders were more severely affected than divers.

  5. Key factors in the design of a LED volumetric 3D display system

    NASA Astrophysics Data System (ADS)

    Lin, Yuanfang; Liu, Xu; Yao, Yi; Zhang, Xiaojie; Liu, Xiangdong; Lin, Fengchun

    2005-01-01

    Through careful consideration of key factors that impact upon voxel attributes and image quality, a volumetric three-dimensional (3D) display system employing the rotation of a two-dimensional (2D) thin active panel was developed. It was designed as a lower-cost 3D visualization platform for experimentation and demonstration. Light emitting diodes (LEDs) were arranged into a 256x64 dot matrix on a single surface of the panel, which was positioned symmetrically about the axis of rotation. The motor and necessary supporting structures were located below the panel. LEDs individually of 500 ns response time, 1.6 mm×0.8 mm×0.6 mm external dimensions, 0.38 mm×0.43 mm horizontal and vertical spacing were adopted. The system is functional, providing 512×256×64, i.e. over 8 million addressable voxels within a 292 mm×165 mm cylindrical volume at a refresh frequency in excess of 16 Hz. Due to persistence of vision, momentarily addressed voxels will be perceived and fused into a 3D image. Many static or dynamic 3D scenes were displayed, which can be directly viewed from any position with few occlusion zones and dead zones. Important depth cues like binocular disparity and motion parallax are satisfied naturally.

  6. Small molecule modulators of eukaryotic initiation factor 2α kinases, the key regulators of protein synthesis.

    PubMed

    Joshi, Manali; Kulkarni, Abhijeet; Pal, Jayanta K

    2013-11-01

    Eukaryotic initiation factor 2 alpha kinases (eIF-2α kinases) are key mediators of stress response in cells. In mammalian cells, there are four eIF-2α kinases, namely HRI (Heme-Regulated Inhibitor), PKR (RNA-dependent Protein Kinase), PERK (PKR-like ER Kinase) and GCN2 (General Control Non-derepressible 2). These kinases get activated during diverse cytoplasmic stress conditions and phosphorylate the alpha-subunit of eIF2, leading to global protein synthesis inhibition. Therefore, eIF-2α kinases play a vital role in various cellular processes such as proliferation, differentiation, apoptosis and cell signaling. Deregulation of eIF-2α kinases and protein synthesis has been linked to numerous pathological conditions such as certain cancers, anemia and neurodegenerative disorders. Thus, modulation of these kinases by small molecules holds a great therapeutic promise. In this review we have compiled the available information on inhibitors and activators of these four eIF-2α kinases. The review concludes with a note on the selectivity issue of currently available modulators and future perspectives for the design of specific small molecule probes.

  7. Caudal, a key developmental regulator, is a DPE-specific transcriptional factor.

    PubMed

    Juven-Gershon, Tamar; Hsu, Jer-Yuan; Kadonaga, James T

    2008-10-15

    The regulation of gene transcription is critical for the proper development and growth of an organism. The transcription of protein-coding genes initiates at the RNA polymerase II core promoter, which is a diverse module that can be controlled by many different elements such as the TATA box and downstream core promoter element (DPE). To understand the basis for core promoter diversity, we explored potential biological functions of the DPE. We found that nearly all of the Drosophila homeotic (Hox) gene promoters, which lack TATA-box elements, contain functionally important DPE motifs that are conserved from Drosophila melanogaster to Drosophila virilis. We then discovered that Caudal, a sequence-specific transcription factor and key regulator of the Hox gene network, activates transcription with a distinct preference for the DPE relative to the TATA box. The specificity of Caudal activation for the DPE is particularly striking when a BRE(u) core promoter motif is associated with the TATA box. These findings show that Caudal is a DPE-specific activator and exemplify how core promoter diversity can be used to establish complex regulatory networks.

  8. Key Factors in the Success of an Organization's Information Security Culture: A Quantitative Study and Analysis

    ERIC Educational Resources Information Center

    Pierce, Robert E.

    2012-01-01

    This research study reviewed relative literature on information security and information security culture within organizations to determine what factors potentially assist an organization in implementing, integrating, and maintaining a successful organizational information security culture. Based on this review of literature, five key factors were…

  9. Environmental impact and risk assessments and key factors contributing to the overall uncertainties.

    PubMed

    Salbu, Brit

    2016-01-01

    , ignoring sensitive history life stages of organisms and transgenerational effects. To link sources, ecosystem transfer and biological effects to future impact and risks, a series of models are usually interfaced, while uncertainty estimates are seldom given. The model predictions are, however, only valid within the boundaries of the overall uncertainties. Furthermore, the model predictions are only useful and relevant when uncertainties are estimated, communicated and understood. Among key factors contributing most to uncertainties, the present paper focuses especially on structure uncertainties (model bias or discrepancies) as aspects such as particle releases, ecosystem dynamics, mixed exposure, sensitive life history stages and transgenerational effects, are usually ignored in assessment models. Research focus on these aspects should significantly reduce the overall uncertainties in the impact and risk assessment of radioactive contaminated ecosystems.

  10. [Anabolic/catabolic imbalance in chronic heart failure].

    PubMed

    Cittadini, Antonio; Bossone, Eduardo; Marra, Alberto Maria; Arcopinto, Michele; Bobbio, Emanuele; Longobardi, Salvatore; Cevara, Carmine; Di Michele, Sara; Saccà, Luigi

    2010-06-01

    A metabolic imbalance between anabolic drive and catabolic forces is commonly observed in chronic heart failure (CHF) patients, with the latter prevailing over anabolic hormones. Moreover, anabolic deficiencies are independent markers of poor prognosis. This finding represents a solid background for the implementation of therapeutic trials based on replacement therapy. The somatotropic axis (GH/IGF-1) is the most powerful anabolic axis of the body and its decline is related with a poor outcome and a worse clinical status. Growth hormone (GH) administration may enter the therapeutic arena as adjunctive treatment in patients affected by CHF and GH/IGF-1 deficiency. The T.O.S.CA. project aims at investigating the relationship between CHF and hormonal deficiency.

  11. Multiple arterial thromboses associated with anabolic androgenic steroids.

    PubMed

    McCulloch, Neil Arthur; Abbas, Jonathan Raihan; Simms, Malcolm Harold

    2014-03-01

    The use of supraphysiological doses of anabolic androgenic steroids can have serious side effects. This article reports the case of a young man who suffered potentially life-threatening arterial thromboses following the use of these drugs.

  12. Detection of anabolic steroid abuse using a yeast transactivation system.

    PubMed

    Zierau, Oliver; Lehmann, Sylvi; Vollmer, Günter; Schänzer, Willhelm; Diel, Patrick

    2008-10-01

    The classical analytical method for detection of anabolic steroid abuse is gas chromatography followed by mass spectrometry (GC/MS). However, even molecules with a chemical structure typical for this class of substances, are sometimes not identified in routine screening by GC/MS when their precise chemical structure is still unknown. A supplementary approach to identify anabolic steroid abuse could be a structure-independent identification of anabolic steroids based on their biological activity. To test the suitability of such a system, we have analyzed the yeast androgen receptor (AR) reporter gene system to identify anabolic steroids in human urine samples. Analysis of different anabolic steroids dissolved in buffer demonstrated that the yeast reporter gene system is able to detect a variety of different anabolic steroids and their metabolites with high specificity, including the so-called 'designer steroid' tetrahydrogestrinone. In contrast, other non-androgenic steroids, like glucocordicoids, progestins, mineralocordicoids and estrogens had a low potency to stimulate transactivation. To test whether the system would also allow the detection of androgens in urine, experiments with spiked urine samples were performed. The androgen reporter gene in yeast responds very sensitive to 5alpha-dihydrotestosterone (DHT), even at high urine concentrations. To examine whether the test system would also be able to detect anabolic steroids in the urine of anabolic steroid abusers, anonymous urine samples previously characterized by GCMS were analyzed with the reporter gene assay. Even when the concentration of the anabolic metabolites was comparatively low in some positive samples it was possible to identify the majority of positive samples by their biological activity. In conclusion, our results demonstrate that the yeast reporter gene system detects anabolic steroids and corresponding metabolites with high sensitivity even in urine of anabolic steroid abusing athletes

  13. Brain connectivity aberrations in anabolic-androgenic steroid users.

    PubMed

    Westlye, Lars T; Kaufmann, Tobias; Alnæs, Dag; Hullstein, Ingunn R; Bjørnebekk, Astrid

    2017-01-01

    Sustained anabolic-androgenic steroid (AAS) use has adverse behavioral consequences, including aggression, violence and impulsivity. Candidate mechanisms include disruptions of brain networks with high concentrations of androgen receptors and critically involved in emotional and cognitive regulation. Here, we tested the effects of AAS on resting-state functional brain connectivity in the largest sample of AAS-users to date. We collected resting-state functional magnetic resonance imaging (fMRI) data from 151 males engaged in heavy resistance strength training. 50 users tested positive for AAS based on the testosterone to epitestosterone (T/E) ratio and doping substances in urine. 16 previous users and 59 controls tested negative. We estimated brain network nodes and their time-series using ICA and dual regression and defined connectivity matrices as the between-node partial correlations. In line with the emotional and behavioral consequences of AAS, current users exhibited reduced functional connectivity between key nodes involved in emotional and cognitive regulation, in particular reduced connectivity between the amygdala and default-mode network (DMN) and between the dorsal attention network (DAN) and a frontal node encompassing the superior and inferior frontal gyri (SFG/IFG) and the anterior cingulate cortex (ACC), with further reductions as a function of dependency, lifetime exposure, and cycle state (on/off).

  14. Dying to be big: a review of anabolic steroid use.

    PubMed Central

    Perry, H M; Wright, D; Littlepage, B N

    1992-01-01

    Anabolic steroids use is commonly perceived to be the domain of the higher echelons of competitive athletes. However, a great deal of anabolic steroid use occurs in private gymnasia (non-local authority) among non-competitive recreational athletes. Our study has attempted to give an insight into the prevalence of the use of these drugs, the hazards associated with it, and the public health responses which we have adopted. PMID:1490220

  15. Phytochrome C is a key factor controlling long-day flowering in barley.

    PubMed

    Nishida, Hidetaka; Ishihara, Daisuke; Ishii, Makoto; Kaneko, Takuma; Kawahigashi, Hiroyuki; Akashi, Yukari; Saisho, Daisuke; Tanaka, Katsunori; Handa, Hirokazu; Takeda, Kazuyoshi; Kato, Kenji

    2013-10-01

    The spring-type near isogenic line (NIL) of the winter-type barley (Hordeum vulgare ssp. vulgare) var. Hayakiso 2 (HK2) was developed by introducing VERNALIZATION-H1 (Vrn-H1) for spring growth habit from the spring-type var. Indo Omugi. Contrary to expectations, the spring-type NIL flowered later than winter-type HK2. This phenotypic difference was controlled by a single gene, which cosegregated only with phytochrome C (HvPhyC) among three candidates around the Vrn-H1 region (Vrn-H1, HvPhyC, and CASEIN KINASE IIα), indicating that HvPhyC was the most likely candidate gene. Compared with the late-flowering allele HvPhyC-l from the NIL, the early-flowering allele HvPhyC-e from HK2 had a single nucleotide polymorphism T1139C in exon 1, which caused a nonsynonymous amino acid substitution of phenylalanine at position 380 by serine in the functionally essential GAF (3', 5'-cyclic-GMP phosphodiesterase, adenylate cyclase, formate hydrogen lyase activator protein) domain. Functional assay using a rice (Oryza sativa) phyA phyC double mutant line showed that both of the HvPhyC alleles are functional, but HvPhyC-e may have a hyperfunction. Expression analysis using NILs carrying HvPhyC-e and HvPhyC-l (NIL [HvPhyC-e] and NIL [HvPhyC-l], respectively) showed that HvPhyC-e up-regulated only the flowering promoter FLOWERING LOCUS T1 by bypassing the circadian clock genes and flowering integrator CONSTANS1 under a long photoperiod. Consistent with the up-regulation, NIL (HvPhyC-e) flowered earlier than NIL (HvPhyC-l) under long photoperiods. These results implied that HvPhyC is a key factor to control long-day flowering directly.

  16. Rhoptry protein 5 (ROP5) Is a Key Virulence Factor in Neospora caninum

    PubMed Central

    Ma, Lei; Liu, Jing; Li, Muzi; Fu, Yong; Zhang, Xiao; Liu, Qun

    2017-01-01

    Neospora caninum, of the Apicomplexa phylum, is a common cause of abortions in cattle and nervous system dysfunction in dogs. Rhoptry proteins of Apicomplexa play an important role in virulence. The objectives of this study were to study functions of NcROP5 in N. caninum by deleting the NcROP5 gene from the wild Nc-1 strain. We selected NcROP5 in ToxoDB and successfully constructed an NcROP5 gene-deleted vector, pTCR-NcROP5-CD KO. Then we screened the NcROP5 knockout strains (ΔNcROP5) at the gene, protein and transcription levels. Plaque assay, host cell invasion assay and intracellular proliferation test showed that the ΔNcROP5 strain had less plaque space, weakened invasion capacity and slower intracellular growth. Animal testing showed significantly lower cerebral load of ΔNcROP5 than the load of the Nc-1 strain, as well as a loss of virulence for the ΔNcROP5 strains. Phenotypic analyses using the label-free LC-MS/MS assay-based proteomic method and KEGG pathway enrichment analysis showed a reduction of NcGRA7 transcription and altered expression of multiple proteins including the apicomplexan family of binding proteins. The present study indicated that ROP5 is a key virulence factor in N. caninum in mice. The proteomic profiling of Nc-1 and ΔNcROP5 provided some data on differential proteins. These data provide a foundation for future research of protein functions in N. caninum. PMID:28326073

  17. Lipid shape is a key factor for membrane interactions of amphipathic helical peptides.

    PubMed

    Strandberg, Erik; Tiltak, Deniz; Ehni, Sebastian; Wadhwani, Parvesh; Ulrich, Anne S

    2012-07-01

    The membrane alignment of the amphiphilic alpha-helical model peptide MSI-103 (sequence [KIAGKIA]3-NH2) was examined by solid state 2H-NMR in different lipid systems by systematically varying the acyl chain length and degree of saturation, the lipid head group type, and the peptide-to-lipid molar ratio. In liquid crystalline phosphatidylcholine (PC) lipids with saturated chains, the amphiphilic helix changes its orientation from a surface-bound "S-state" to a tilted "T-state" with increasing peptide concentration. In PC lipids with unsaturated chains, on the other hand, the S-state is found throughout all concentrations. Using phosphatidylethanolamine lipids with a small head group or by addition of lyso-lipids with only one acyl chain, the spontaneous curvature of the bilayer was purposefully changed. In the first case with a negative curvature only the S-state was found, whereas in systems with a positive curvature the peptide preferred the obliquely immersed T-state at high concentration. The orientation of MSI-103 thus correlates very well with the shape of the lipid molecules constituting the membrane. Lipid charge, on the other hand, was found to affect only the initial electrostatic attraction to the membrane surface but not the alignment preferences. In bilayers that are "sealed" with 20% cholesterol, MSI-103 cannot bind in a well-oriented manner and forms immobilized aggregates instead. We conclude that the curvature properties of a membrane are a key factor in the interactions of amphiphilic helical peptides in general, whose re-alignment and immersion preferences may thus be inferred in a straightforward manner from the lipid-shape concept.

  18. Process and kinetics of azo dye decolourization in bioelectrochemical systems: effect of several key factors

    PubMed Central

    Yang, Hou-Yun; He, Chuan-Shu; Li, Lei; Zhang, Jie; Shen, Jin-You; Mu, Yang; Yu, Han-Qing

    2016-01-01

    This study explored the influence of several key factors on the process and kinetics of azo dye decolourization in bioelectrochemical systems (BESs), including cathode potential, dissolved oxygen (DO) concentration of catholyte and biofilm formed on the cathode. The results show that azo dye methyl orange (MO) decolourization in the BES could be well described with the pseudo first-order kinetics. The MO decolourization efficiency increased from 0 to 94.90 ± 0.01% and correspondingly the reaction rate constant increased from 0 to 0.503 ± 0.001 h−1 with the decrease in cathodic electrode potential from −0.2 to −0.8 V vs Ag/AgCl. On the contrary, DO concentration of the catholyte had a negative impact on MO decolourization in the BES. When DO concentration increased from zero to 5.80 mg L−1, the MO decolourization efficiency decreased from 87.19 ± 4.73% to 27.77 ± 0.06% and correspondingly the reaction rate constant reduced from 0.207 ± 0.042 to 0.033 ± 0.007 h−1. Additionally, the results suggest that the biofilm formed on the cathode could led to an adverse rather than a positive effect on azo dye decolourization in the BES in terms of efficiency and kinetics. PMID:27270398

  19. Socioeconomic status, family background and other key factors influence the management of head lice in Norway.

    PubMed

    Rukke, Bjørn Arne; Soleng, Arnulf; Lindstedt, Heidi Heggen; Ottesen, Preben; Birkemoe, Tone

    2014-05-01

    How head lice infestations are managed by households is an important but generally neglected issue in head lice research. In the present study, we investigate actions taken against head lice by Norwegian households in association with socioeconomic status, family background, school-related variables and other key factors. Repeat questionnaires distributed to caretakers of the same elementary school children during a 2-year period enabled us to study both previous head lice management and any changes in this management through time. Households from 12 schools spanning the main socioeconomic variation found in Norway participated in the study. All students with active head lice infestation were treated in the four investigated periods. Most caretakers used a thorough head lice checking technique and informed others of own infestation. Checking frequency was low as most children were inspected less than monthly. The best determinant of increased checking frequency and thoroughness was personal experience with head lice. The increased awareness, however, seemed to be somewhat short-lived, as there was a decrease in checking frequency and thoroughness within 1 year after infestation. Personal experience with head lice also increased general knowledge related to the parasite. Parents born in developing countries checked their children for head lice more frequently, although less thoroughly, informed fewer contacts when infested, used pediculicides preventively more often and knew less about head lice than parents born in developed countries. Households with highly educated mothers had a lower checking frequency, but their knowledge and willingness to inform others was high. Single parents were more concerned about economic costs and kept children home from school longer while infested than other parents. As head lice management varied among socioeconomic groups and with parental background, differentiated advice should be considered in the control of head lice. The

  20. Measurement of immunotargeted plasmonic nanoparticles' cellular binding: a key factor in optimizing diagnostic efficacy

    NASA Astrophysics Data System (ADS)

    Fu, Kun; Sun, Jiantang; Bickford, Lissett R.; Lin, Alex W. H.; Halas, Naomi J.; Yu, Tse-Kuan; Drezek, Rebekah A.

    2008-01-01

    In this study, we use polarized light scattering to study immunotargeted plasmonic nanoparticles which bind to live SK-BR-3 human breast carcinoma cells. Gold nanoparticles can be conjugated to various biomolecules in order to target specific molecular signatures of disease. This specific targeting provides enhanced contrast in scattering-based optical imaging techniques. While there are papers which report the number of antibodies that bind per nanoparticle, there are almost no reports of the key factor which influences diagnostic or therapeutic efficacy using nanoparticles: the number of targeted nanoparticles that bind per cell. To achieve this goal, we have developed a 'negative' method of determining the binding concentration of those antibody/nanoparticle bioconjugates which are targeted specifically to breast cancer cells. Unlike previously reported methods, we collected unbound nanoparticle bioconjugates and measured the light scattering from dilute solutions of these particles so that quantitative binding information can be obtained. By following this process, the interaction effects of adjacent bound nanoparticles on the cell membrane can be avoided simply by measuring the light scattering from the unbound nanoparticles. Specifically, using nanoshells of two different sizes, we compared the binding concentrations of anti-HER2/nanoshell and anti-IgG/nanoshell bioconjugates targeted to HER2-positive SK-BR-3 breast cancer cells. The results indicate that, for anti-HER2/nanoshell bioconjugates, there are approximately 800-1600 nanoshells bound per cell; for anti-IgG/nanoshell bioconjugates, the binding concentration is significantly lower at nearly 100 nanoshells bound per cell. These results are also supported by dark-field microscopy images of the cells labeled with anti-HER2/nanoshell and anti-IgG/nanoshell bioconjugates.

  1. Interlocking of chelae is a key factor for dominance hierarchy formation in crayfish.

    PubMed

    Ueno, Ryusuke; Nagayama, Toshiki

    2012-08-15

    We characterized the role of chelae during agonistic encounters of the crayfish Procambarus clarkii. Physical asymmetries in body length, body mass and chelae size were directly related to dominance hierarchy formation. More than 80% of winning crayfish had longer body and chelae lengths, and winners were usually heavier in body mass, even if their differences were less than 3% compared with losing opponents. In mismatched pairings, large crayfish with short chelae were beaten by small crayfish with large chelae. Three physical elements of body length, body mass and chelae length equally affected the outcome of agonistic bouts. Chelae restriction, in which chelae were tightly closed using rubber bands, affected the outcome of agonistic bouts between large and small crayfish. Before chelae restriction, large crayfish won in all pairings. Following chelae restriction for at least 30 days from the first encounters, the winning rate of large crayfish that were previous winners decreased significantly in the second encounters against the same opponents that were previous losers. The handicap of chelae restriction significantly prolonged the time to formation of the winner-loser relationship. Individual fights escalated during agonistic bouts between large crayfish with one chela restricted and small crayfish with intact chelae, whereas the number of fights increased but the duration of individual fights did not increase in large crayfish with both chelae restricted. Furthermore, when the chelae of both large and small crayfish were disabled, the dominance order was frequently not formed during 30 min of agonistic bouts. Preventing chelae from interlocking prevented escalation of agonistic bouts. We show that interlocking of chelae acted as a key factor for the formation of dominance hierarchy.

  2. Soil physical properties: Key factors for successful reclamation of disturbed landscapes

    NASA Astrophysics Data System (ADS)

    Krümmelbein, Julia; Raab, Thomas

    2013-04-01

    The practice of open cast mining, e.g. for lignite, results in major landscape disturbances and especially affects soils because relocation and subsequent mixing of naturally developed soil horizons leads to areas with extremely altered soil properties compared to the undisturbed conditions. Various reclamation measures are applied to recover the reconstructed landscape for different land use options. Major parts of the post mining landscapes are used for agriculture, agroforestry or silviculture, the remaining voids of the coal mines fill successively with groundwater after mine closure and are or will be used mainly for touristic and leisure purposes. Small proportions of the post mining areas are left for natural succession, or habitats for endangered flora and fauna are initiated. In reclamation research, many studies have focused on soil chemical and biological constraints of post mining substrates and investigated factors such as unsuitable pH, in many cases very low pH, (poor) nutrient contents and (poor) biological activity. But the initial and developing soil physical parameters and functions are also key factors for the success of reclamation practices. The soil water and gas balance influence strongly the suitability of a site for the intended future land use. The mechanical stability of the soil determines the rigidity of the pore system against deforming forces and thereby the persistence of soil functions, such as water and air permeability over time. The amendment of unfavourable (initial) soil physical properties is in most cases more complex and time-consuming than e.g. optimization of pH or fertilization with nutrients. Moreover, regarding the suitability of a site e.g. as a habitat for plants or microorganisms, poor physical pre-conditions can turn substrates with perfect nutrient contents and composition and pH into infertile locations of very low productivity. We show results of an on-going field study where the effects of different

  3. Hypoxia Potentiates Anabolic Effects of Exogenous Hyaluronic Acid in Rat Articular Cartilage

    PubMed Central

    Ichimaru, Shohei; Nakagawa, Shuji; Arai, Yuji; Kishida, Tsunao; Shin-Ya, Masaharu; Honjo, Kuniaki; Tsuchida, Shinji; Inoue, Hiroaki; Fujiwara, Hiroyoshi; Shimomura, Seiji; Mazda, Osam; Kubo, Toshikazu

    2016-01-01

    Hyaluronic acid (HA) is used clinically to treat osteoarthritis (OA), but its pharmacological effects under hypoxic conditions remain unclear. Articular chondrocytes in patients with OA are exposed to a hypoxic environment. This study investigated whether hypoxia could potentiate the anabolic effects of exogenous HA in rat articular cartilage and whether these mechanisms involved HA receptors. HA under hypoxic conditions significantly enhanced the expression of extracellular matrix genes and proteins in explant culture, as shown by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and dimethylmethylene blue (DMMB) assays. Staining with Safranin-O and immunohistochemical staining with antibody to type II collagen were also enhanced in pellet culture. The expression of CD44 was increased by hypoxia and significantly suppressed by transfection with siRNAs targeting hypoxia-inducible factor 1 alpha (siHIF-1α). These findings indicate that hypoxia potentiates the anabolic effects of exogenous HA by a mechanism in which HIF-1α positively regulates the expression of CD44, enhancing the binding affinity for exogenous HA. The anabolic effects of exogenous HA may increase as OA progresses. PMID:27347945

  4. Cardiac autonomic dysfunction in anabolic steroid users.

    PubMed

    Maior, A S; Carvalho, A R; Marques-Neto, S R; Menezes, P; Soares, P P; Nascimento, J H M

    2013-10-01

    This study aimed to evaluate if androgenic-anabolic steroids (AAS) abuse may induce cardiac autonomic dysfunction in recreational trained subjects. Twenty-two men were volunteered for the study. The AAS group (n = 11) utilized AAS at mean dosage of 410 ± 78.6 mg/week. All of them were submitted to submaximal exercise testing using an Astrand-Rhyming protocol. Electrocardiogram (ECG) and respired gas analysis were monitored at rest, during, and post-effort. Mean values of VO2 , VCO2 , and VE were higher in AAS group only at rest. The heart rate variability variables were calculated from ECG using MATLAB-based algorithms. At rest, AAS group showed lower values of the standard deviation of R-R intervals, the proportion of adjacent R-R intervals differing by more than 50 ms (pNN50), the root mean square of successive differences (RMSSD), and the total, the low-frequency (LF) and the high-frequency (HF) spectral power, as compared to Control group. After submaximal exercise testing, pNN50, RMSSD, and HF were lower, and the LF/HF ratio was higher in AAS group when compared to control group. Thus, the use of supraphysiological doses of AAS seems to induce dysfunction in tonic cardiac autonomic regulation in recreational trained subjects.

  5. Illicit Anabolic-Androgenic Steroid Use

    PubMed Central

    Kanayama, Gen; Hudson, James I.; Pope, Harrison G.

    2009-01-01

    The anabolic-androgenic steroids (AAS) are a family of hormones that includes testosterone and its derivatives. These substances have been used by elite athletes since the 1950s, but they did not become widespread drugs of abuse in the general population until the 1980s. Thus, knowledge of the medical and behavioral effects of illicit AAS use is still evolving. Surveys suggest that many millions of boys and men, primarily in Western countries, have abused AAS to enhance athletic performance or personal appearance. AAS use among girls and women is much less common. Taken in supraphysiologic doses, AAS show various long-term adverse medical effects, especially cardiovascular toxicity. Behavioral effects of AAS include hypomanic or manic symptoms, sometimes accompanied by aggression or violence, which usually occur while taking AAS, and depressive symptoms occurring during AAS withdrawal. However, these symptoms are idiosyncratic and afflict only a minority of illicit users; the mechanism of these idiosyncratic responses remains unclear. AAS users may also ingest a range of other illicit drugs, including both “body-image” drugs to enhance physical appearance or performance, and classical drugs of abuse. In particular, AAS users appear particularly prone to opioid use. There may well be a biological basis for this association, since both human and animal data suggest that AAS and opioids may share similar brain mechanisms. Finally, AAS may cause a dependence syndrome in a substantial minority of users. AAS dependence may pose a growing public health problem in future years, but remains little studied. PMID:19769977

  6. Anabolic-androgenic steroids and the adolescent.

    PubMed

    Rogol, A D; Yesalis, C E

    1992-03-01

    This article has reviewed some of the hormonal and behavioral maturation that occurs during adolescence, which are characterized by remarkable physical changes and behavioral vulnerability. Risk taking of many varieties is common and drugs (including anabolic-androgenic steroids) form a part of the prevailing culture in many places. These steroids probably are not severe health hazards when taken intermittently and in low to moderate doses. The 17-alkylated derivatives are clearly the more likely to cause hepatotoxicity. Thus, the scare tactics formerly used (severe constitutional side effects) are doomed to failure. The tenuous link between these drugs and objective behavioral and addictive effects must be strengthened before health strategies based on this issue can be validated. Clearly, the lack of scientific information has impeded, if not precluded, the formulation of an effective health education strategy. The most potent deterrent to the use of steroid drugs by athletes must be the moral issue of fair play and maintaining a "level playing field." We strongly support directed research in these areas and hope that the credibility of the scientific community can be regained after its faulted "stop steroid use" campaigns based on the lack of steroid efficacy in bringing about desired results or on their dire consequences have been replaced with credible evidence to refute their use on these and other grounds.

  7. Distributed Factorization Computation on Multiple Volunteered Mobile Resource to Break RSA Key

    NASA Astrophysics Data System (ADS)

    Jaya, I.; Hardi, S. M.; Tarigan, J. T.; Zamzami, E. M.; Sihombing, P.

    2017-01-01

    Similar to common asymmeric encryption, RSA can be cracked by usmg a series mathematical calculation. The private key used to decrypt the massage can be computed using the public key. However, finding the private key may require a massive amount of calculation. In this paper, we propose a method to perform a distributed computing to calculate RSA’s private key. The proposed method uses multiple volunteered mobile devices to contribute during the calculation process. Our objective is to demonstrate how the use of volunteered computing on mobile devices may be a feasible option to reduce the time required to break a weak RSA encryption and observe the behavior and running time of the application on mobile devices.

  8. Phytochrome C Is A Key Factor Controlling Long-Day Flowering in Barley1[W

    PubMed Central

    Nishida, Hidetaka; Ishihara, Daisuke; Ishii, Makoto; Kaneko, Takuma; Kawahigashi, Hiroyuki; Akashi, Yukari; Saisho, Daisuke; Tanaka, Katsunori; Handa, Hirokazu; Takeda, Kazuyoshi; Kato, Kenji

    2013-01-01

    The spring-type near isogenic line (NIL) of the winter-type barley (Hordeum vulgare ssp. vulgare) var. Hayakiso 2 (HK2) was developed by introducing VERNALIZATION-H1 (Vrn-H1) for spring growth habit from the spring-type var. Indo Omugi. Contrary to expectations, the spring-type NIL flowered later than winter-type HK2. This phenotypic difference was controlled by a single gene, which cosegregated only with phytochrome C (HvPhyC) among three candidates around the Vrn-H1 region (Vrn-H1, HvPhyC, and CASEIN KINASE IIα), indicating that HvPhyC was the most likely candidate gene. Compared with the late-flowering allele HvPhyC-l from the NIL, the early-flowering allele HvPhyC-e from HK2 had a single nucleotide polymorphism T1139C in exon 1, which caused a nonsynonymous amino acid substitution of phenylalanine at position 380 by serine in the functionally essential GAF (3′, 5′-cyclic-GMP phosphodiesterase, adenylate cyclase, formate hydrogen lyase activator protein) domain. Functional assay using a rice (Oryza sativa) phyA phyC double mutant line showed that both of the HvPhyC alleles are functional, but HvPhyC-e may have a hyperfunction. Expression analysis using NILs carrying HvPhyC-e and HvPhyC-l (NIL [HvPhyC-e] and NIL [HvPhyC-l], respectively) showed that HvPhyC-e up-regulated only the flowering promoter FLOWERING LOCUS T1 by bypassing the circadian clock genes and flowering integrator CONSTANS1 under a long photoperiod. Consistent with the up-regulation, NIL (HvPhyC-e) flowered earlier than NIL (HvPhyC-l) under long photoperiods. These results implied that HvPhyC is a key factor to control long-day flowering directly. PMID:24014575

  9. Biological activity in Technosols as a key factor of their structure

    NASA Astrophysics Data System (ADS)

    Watteau, Françoise; Villemin, Geneviève; Bouchard, Adeline; Monserié, Marie-France; Séré, Geoffroy; Schwartz, Christophe; Morel, Jean-Louis

    2010-05-01

    )availability. HAP also contributed to the aggregation of technogenic constituents in Technosol 1. The biological activity generated by the presence of exogenous organic matter is thus in short (0-2 years) and mean (30 years) terms, a key factor of the structuration and by there of the pedogenesis of Technosols.

  10. On the Security of a Two-Factor Authentication and Key Agreement Scheme for Telecare Medicine Information Systems.

    PubMed

    Arshad, Hamed; Teymoori, Vahid; Nikooghadam, Morteza; Abbassi, Hassan

    2015-08-01

    Telecare medicine information systems (TMISs) aim to deliver appropriate healthcare services in an efficient and secure manner to patients. A secure mechanism for authentication and key agreement is required to provide proper security in these systems. Recently, Bin Muhaya demonstrated some security weaknesses of Zhu's authentication and key agreement scheme and proposed a security enhanced authentication and key agreement scheme for TMISs. However, we show that Bin Muhaya's scheme is vulnerable to off-line password guessing attacks and does not provide perfect forward secrecy. Furthermore, in order to overcome the mentioned weaknesses, we propose a new two-factor anonymous authentication and key agreement scheme using the elliptic curve cryptosystem. Security and performance analyses demonstrate that the proposed scheme not only overcomes the weaknesses of Bin Muhaya's scheme, but also is about 2.73 times faster than Bin Muhaya's scheme.

  11. A Comprehensive Test of General Strain Theory: Key Strains, Situational- and Trait-Based Negative Emotions, Conditioning Factors, and Delinquency

    ERIC Educational Resources Information Center

    Moon, Byongook; Morash, Merry; McCluskey, Cynthia Perez; Hwang, Hye-Won

    2009-01-01

    Using longitudinal data on South Korean youth, the authors addressed limitations of previous tests of general strain theory (GST), focusing on the relationships among key strains, situational- and trait-based negative emotions, conditioning factors, and delinquency. Eight types of strain previously shown most likely to result in delinquency,…

  12. Repeated anabolic-androgenic steroid treatment during adolescence increases vasopressin V(1A) receptor binding in Syrian hamsters: correlation with offensive aggression.

    PubMed

    DeLeon, Katrina R; Grimes, Jill M; Melloni, Richard H

    2002-09-01

    Repeated anabolic-androgenic steroid treatment during adolescence increases hypothalamic vasopressin and facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus). The current study investigated whether anabolic-androgenic steroid exposure during this developmental period influenced vasopressin V(1A) receptor binding activity in the hypothalamus and several other brain areas implicated in aggressive behavior in hamsters. To test this, adolescent male hamsters were administered anabolic steroids or sesame oil throughout adolescence, tested for offensive aggression, and examined for differences in vasopressin V(1A) receptor binding using in situ autoradiography. When compared with control animals, aggressive, adolescent anabolic steroid-treated hamsters showed significant increases (20-200%) in the intensity of vasopressin V(1A) receptor labeling in several aggression areas, including the ventrolateral hypothalamus, bed nucleus of the stria terminalis, and lateral septum. However, no significant differences in vasopressin V(1A) receptor labeling were found in other brain regions implicated in aggressive responding, most notably the lateral zone from the medial preoptic area to anterior hypothalamus and the corticomedial amygdala. These data suggest that adolescent anabolic steroid exposure may facilitate offensive aggression by increasing vasopressin V(1A) receptor binding in several key areas of the hamster brain.

  13. Androgenic anabolic steroid use among male adolescents in Falkenberg.

    PubMed

    Nilsson, S

    1995-01-01

    Recent reports show that androgenic anabolic steroids are used by many teenagers, not as a deliberate attempt to give them strength, better athletic performance, etc., but to improve their looks. The so-called macho cult among young boys tempts them into using androgenic anabolic steroids to give them bigger muscles and a more powerful appearance. This study was undertaken to investigate the prevalence of androgenic anabolic steroid use among teenagers in a small town and to create a platform for future work with the aim of decreasing the misuse of these drugs. In Falkenberg, a town in the county of Halland in the west of Sweden, the pupils at two high schools were investigated by means of an anonymous multiple-choice questionnaire. A total of 1383 students (688 males and 695 females) aged 14-19 years participated in the study, giving a participation rate of 96%. The number of answers completed was 99%. The use of androgenic anabolic steroids is a reality among male teenagers in Falkenberg, with 5.8% of them using the drugs. Among 15- to 16-year-old boys misuse of these drugs is as high as 10%, and of these 50% (5.0% of total) also inject ampoules of the drugs. This prevalence is alarming since the adverse effects of androgenic anabolic steroids are more serious in teenagers. Serious action must be taken to inform teenagers of the consequences of misusing drugs.

  14. Local Text Cohesion, Reading Ability and Individual Science Aspirations: Key Factors Influencing Comprehension in Science Classes

    ERIC Educational Resources Information Center

    Hall, Sophie S.; Kowalski, Rebecca; Paterson, Kevin B.; Basran, Jaskaran; Filik, Ruth; Maltby, John

    2015-01-01

    In response to the concern of the need to improve the scientific skills of school children, this study investigated the influence of text design (in terms of text cohesion) and individual differences, with the aim of identifying pathways to improving science education in early secondary school (Key Stage 3). One hundred and four secondary school…

  15. Key Factors to Instructors' Satisfaction of Learning Management Systems in Blended Learning

    ERIC Educational Resources Information Center

    Al-Busaidi, Kamla Ali; Al-Shihi, Hafedh

    2012-01-01

    Learning Management System (LMS) enables institutions to administer their educational resources, and support their traditional classroom education and distance education. LMS survives through instructors' continuous use, which may be to a great extent associated with their satisfaction of the LMS. Consequently, this study examined the key factors…

  16. Drug packaging. A key factor to be taken into account when choosing a treatment.

    PubMed

    2011-10-01

    A drug's packaging contributes to its harm-benefit balance. Highlighting the key practical information and identifying potential sources of error or mix-ups is part and parcel of the correct use of medicines. Select labelling that clearly and prominently displays the important information, including the international nonproprietary name (INN).

  17. Role of Education in Rural Development: A Key Factor for Developing Countries.

    ERIC Educational Resources Information Center

    Navaratnam, Kathiravelu K.

    Relevent, locally-controlled educational programs play key roles in rural development in developing nations. Education has a desirable controlling influence over development of the rural individual, family, community, and society, leading to reduced poverty, income equity, and controlled unemployment. The failure of trickle-down development and…

  18. Key factors influencing ADME properties of therapeutic proteins: A need for ADME characterization in drug discovery and development

    PubMed Central

    Tibbitts, Jay; Canter, David; Graff, Ryan; Smith, Alison; Khawli, Leslie A.

    2016-01-01

    abstract Protein therapeutics represent a diverse array of biologics including antibodies, fusion proteins, and therapeutic replacement enzymes. Since their inception, they have revolutionized the treatment of a wide range of diseases including respiratory, vascular, autoimmune, inflammatory, infectious, and neurodegenerative diseases, as well as cancer. While in vivo pharmacokinetic, pharmacodynamic, and efficacy studies are routinely carried out for protein therapeutics, studies that identify key factors governing their absorption, distribution, metabolism, and excretion (ADME) properties have not been fully investigated. Thorough characterization and in-depth study of their ADME properties are critical in order to support drug discovery and development processes for the production of safer and more effective biotherapeutics. In this review, we discuss the main factors affecting the ADME characteristics of these large macromolecular therapies. We also give an overview of the current tools, technologies, and approaches available to investigate key factors that influence the ADME of recombinant biotherapeutic drugs, and demonstrate how ADME studies will facilitate their future development. PMID:26636901

  19. The Promise of Virtual Teams: Identifying Key Factors in Effectiveness and Failure

    ERIC Educational Resources Information Center

    Horwitz, Frank M.; Bravington, Desmond; Silvis, Ulrik

    2006-01-01

    Purpose: The aim of the investigation is to identify enabling and disenabling factors in the development and operation of virtual teams; to evaluate the importance of factors such as team development, cross-cultural variables, leadership, communication and social cohesion as contributors to virtual team effectiveness. Design/methodology/approach:…

  20. From Loose Groups to Effective Teams: The Nine Key Factors of the Team Landscape.

    ERIC Educational Resources Information Center

    Sheard, A. G.; Kakabadse, A. P.

    2002-01-01

    A loose group of individuals working on a task differs from an effective team on nine factors: clearly defined goals, priorities, roles and responsibilities, self-awareness, leadership, group dynamics, communications, content, and infrastructure. Ways to eliminate barriers and speed formation of effective teams could be based on those factors.…

  1. Exercise-induced neuroprotective effects on neurodegenerative diseases: the key role of trophic factors.

    PubMed

    Campos, Carlos; Rocha, Nuno Barbosa F; Lattari, Eduardo; Paes, Flávia; Nardi, António E; Machado, Sérgio

    2016-06-01

    Age-related neurodegenerative disorders, like Alzheimer's or Parkinson's disease, are becoming a major issue to public health care. Currently, there is no effective pharmacological treatment to address cognitive impairment in these patients. Here, we aim to explore the role of exercise-induced trophic factor enhancement in the prevention or delay of cognitive decline in patients with neurodegenerative diseases. There is a significant amount of evidence from animal and human studies that links neurodegenerative related cognitive deficits with changes on brain and peripheral trophic factor levels. Several trials with elderly individuals and patients with neurodegenerative diseases report exercise induced cognitive improvements and changes on trophic factor levels including BDNF, IGF-I, among others. Further studies with healthy aging and clinical populations are needed to understand how diverse exercise interventions produce different variations in trophic factor signaling. Genetic profiles and potential confounders regarding trophic factors should also be addressed in future trials.

  2. Heat Stress Modulates Both Anabolic and Catabolic Signaling Pathways Preventing Dexamethasone‐Induced Muscle Atrophy In Vitro

    PubMed Central

    Tsuchida, Wakako; Iwata, Masahiro; Akimoto, Takayuki; Matsuo, Shingo; Asai, Yuji

    2016-01-01

    It is generally recognized that synthetic glucocorticoids induce skeletal muscle weakness, and endogenous glucocorticoid levels increase in patients with muscle atrophy. It is reported that heat stress attenuates glucocorticoid‐induced muscle atrophy; however, the mechanisms involved are unknown. Therefore, we examined the mechanisms underlying the effects of heat stress against glucocorticoid‐induced muscle atrophy using C2C12 myotubes in vitro, focusing on expression of key molecules and signaling pathways involved in regulating protein synthesis and degradation. The synthetic glucocorticoid dexamethasone decreased myotube diameter and protein content, and heat stress prevented the morphological and biochemical glucocorticoid effects. Heat stress also attenuated increases in mRNAs of regulated in development and DNA damage responses 1 (REDD1) and Kruppel‐like factor 15 (KLF15). Heat stress recovered the dexamethasone‐induced inhibition of PI3K/Akt signaling. These data suggest that changes in anabolic and catabolic signals are involved in heat stress‐induced protection against glucocorticoid‐induced muscle atrophy. These results have a potentially broad clinical impact because elevated glucocorticoid levels are implicated in a wide range of diseases associated with muscle wasting. J. Cell. Physiol. 232: 650–664, 2017. © 2016 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc. PMID:27649272

  3. [Abuse of anabolic steroids and its impact on thyroid function].

    PubMed

    Fortunato, Rodrigo S; Rosenthal, Doris; Carvalho, Denise P de

    2007-12-01

    The use of anabolic steroids to increase physical performance and for aesthetic ends has reached alarming indices in the last three decades. Besides the desired actions, several collateral effects have been described in the literature, such as the development of some types of cancer, ginecomasty, peliosis hepatis, renal insufficiency, virilization, amongst others. The most proeminent effect on human thyroid function is the reduction of thyroxine binding globulin (TBG), with consequent reductions of total serum T3 and T4, depending however on the susceptibility of the drug to aromatization and subsequent transformation into estrogen. In rats, anabolic steroids also act in the peripheral metabolism of thyroid hormones and seem to exert an important proliferative effect on thyroid cells. Thus, the aim of the present paper is to review data on the effect of supraphysiological doses of anabolic steroids on thyroid function, showing the danger that indiscriminate use of these drugs can cause to health.

  4. A consideration of select pre-trauma factors as key vulnerabilities in PTSD

    PubMed Central

    Bomyea, Jessica; Risbrough, Victoria; Lang, Ariel J.

    2012-01-01

    Posttraumatic stress disorder (PTSD) is a pathological response to a traumatic event. A number of risk and vulnerability factors predicting PTSD development have been identified in the literature. Many of these variables are specific factors occurring during and after exposure to a traumatic event or are not measured prospectively to assess temporal sequence. Recent research, however, has begun to focus on pre-trauma individual differences that could contribute to risk for developing PTSD. The present review proposes that a number of biological and cognitive vulnerability factors place individuals at risk for PTSD development prior to the actual experience of trauma. Accordingly, this review provides a summary of evidence for a select number of these factors as pre-trauma vulnerabilities to PTSD. Included is a discussion of biological factors, including molecular genetic studies of systems regulating serotonin, catecholamines, and glucocorticoids as well as aspects of the neuroendocrine system. Specific cognitive factors are also considered, including intelligence, neuropsychological functioning and cognitive biases such as negative attributional style and appraisals. For each factor, the present review summarizes evidence to date regarding PTSD vulnerability and highlights directions for future research in this area. PMID:22917742

  5. A sensitivity analysis of key natural factors in the modeled global acetone budget

    NASA Astrophysics Data System (ADS)

    Brewer, J. F.; Bishop, M.; Kelp, M.; Keller, C. A.; Ravishankara, A. R.; Fischer, E. V.

    2017-02-01

    Acetone is one of the most abundant carbonyl compounds in the atmosphere, and it serves as an important source of HOx (OH + HO2) radicals in the upper troposphere and a precursor for peroxyacetyl nitrate. We present a global sensitivity analysis targeted at several major natural source and sink terms in the global acetone budget to find the input factor or factors to which the simulated acetone mixing ratio was most sensitive. The ranges of input factors were taken from literature. We calculated the influence of these factors in terms of their elementary effects on model output. Of the six factors tested here, the four factors with the highest contribution to total global annual model sensitivity are direct emissions of acetone from the terrestrial biosphere, acetone loss to photolysis, the concentration of acetone in the ocean mixed layer, and the dry deposition of acetone to ice-free land. The direct emissions of acetone from the terrestrial biosphere are globally important in determining acetone mixing ratios, but their importance varies seasonally outside the tropics. Photolysis is most influential in the upper troposphere. Additionally, the influence of the oceanic mixed layer concentrations are relatively invariant between seasons, compared to the other factors tested. Monoterpene oxidation in the troposphere, despite the significant uncertainties in acetone yield in this process, is responsible for only a small amount of model uncertainty in the budget analysis.

  6. The physical size of transcription factors is key to transcriptional regulation in chromatin domains

    NASA Astrophysics Data System (ADS)

    Maeshima, Kazuhiro; Kaizu, Kazunari; Tamura, Sachiko; Nozaki, Tadasu; Kokubo, Tetsuro; Takahashi, Koichi

    2015-02-01

    Genetic information, which is stored in the long strand of genomic DNA as chromatin, must be scanned and read out by various transcription factors. First, gene-specific transcription factors, which are relatively small (˜50 kDa), scan the genome and bind regulatory elements. Such factors then recruit general transcription factors, Mediators, RNA polymerases, nucleosome remodellers, and histone modifiers, most of which are large protein complexes of 1-3 MDa in size. Here, we propose a new model for the functional significance of the size of transcription factors (or complexes) for gene regulation of chromatin domains. Recent findings suggest that chromatin consists of irregularly folded nucleosome fibres (10 nm fibres) and forms numerous condensed domains (e.g., topologically associating domains). Although the flexibility and dynamics of chromatin allow repositioning of genes within the condensed domains, the size exclusion effect of the domain may limit accessibility of DNA sequences by transcription factors. We used Monte Carlo computer simulations to determine the physical size limit of transcription factors that can enter condensed chromatin domains. Small gene-specific transcription factors can penetrate into the chromatin domains and search their target sequences, whereas large transcription complexes cannot enter the domain. Due to this property, once a large complex binds its target site via gene-specific factors it can act as a ‘buoy’ to keep the target region on the surface of the condensed domain and maintain transcriptional competency. This size-dependent specialization of target-scanning and surface-tethering functions could provide novel insight into the mechanisms of various DNA transactions, such as DNA replication and repair/recombination.

  7. Hepatic lesions in patients treated with synthetic anabolic steriods.

    PubMed

    Sweeney, E C; Evans, D J

    1976-07-01

    Hepatic abnormalities are described in three patients who received synthetic anabolic steroids. A child with Franconi's anaemia was treated for four years and at necropsy the liver showed generalized hyperplasia, hyperplastic nodules, and a benign hepatoma. Two adults received only three months' therapy with synthetic androgens; in one there was generalized hepatic hyperplasia and in the other widespread nodular hyperplasia. It is suggested that anabolic steroids may induce tumours through intermediate hyperplastic lesions, a sequence similar to that seen during tumour induction by carcinogens in experimental animals.

  8. Hepatic lesions in patients treated with synthetic anabolic steriods.

    PubMed Central

    Sweeney, E C; Evans, D J

    1976-01-01

    Hepatic abnormalities are described in three patients who received synthetic anabolic steroids. A child with Franconi's anaemia was treated for four years and at necropsy the liver showed generalized hyperplasia, hyperplastic nodules, and a benign hepatoma. Two adults received only three months' therapy with synthetic androgens; in one there was generalized hepatic hyperplasia and in the other widespread nodular hyperplasia. It is suggested that anabolic steroids may induce tumours through intermediate hyperplastic lesions, a sequence similar to that seen during tumour induction by carcinogens in experimental animals. Images PMID:185239

  9. Anabolic steroids: what should the emergency physician know?

    PubMed

    Brown, James T

    2005-08-01

    Anabolic steroids have not currently made their way into the daily practice of emergency physicians. The patients that use and abuse them have. In addition, those patients that are suffering from the consequences of illnesses that have excess levels of androgens are commonly evaluated in the emergency department. Clinicians should familiarize themselves with the practices of anabolic steroid users, so they can provide more beneficial council to their patients. As research continues, the emergency physician may find uses for androgens within the emergency department.

  10. Bleeding oesophageal varices associated with anabolic steroid use in an athlete.

    PubMed Central

    Winwood, P. J.; Robertson, D. A.; Wright, R.

    1990-01-01

    A 30 year old bodybuilder who had been taking anabolic steroids for 18 months presented with bleeding oesophageal varices. Serious liver disease secondary to anabolic steroids including peliosis hepatis, nodular hyperplasia and malignant change is well recognized. We report what is, to our knowledge, the first case of bleeding oesophageal varices associated with the use of anabolic steroids. PMID:2099434

  11. 21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person...

  12. Knowledge about Anabolic Steroids of Rhode Island Adolescents: Implications for Education Programs.

    ERIC Educational Resources Information Center

    Nutter, June

    Although anabolic steroids are associated with short term behavior and long term health problems, few schools address this issue. Adolescents were surveyed to determine their general knowledge of anabolic steroids, attitudes related to fair play, and interest in limiting anabolic steroid use. Data from 322 boys and 331 girls in grades 7-12 were…

  13. 21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person...

  14. 21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person...

  15. The Effect of Anabolic Steroid Education on Knowledge and Attitudes of At-Risk Preadolescents.

    ERIC Educational Resources Information Center

    Trenhaile, Jay; Choi, Hee-Sook; Proctor, Theron B.; Work, Patricia

    1998-01-01

    Investigates the effect of anabolic steroid education on preadolescents' knowledge of and attitudes toward anabolic steroids with 35 male athletes. Information on psychological and physiological aspects of anabolic steroid use, weight training techniques, nutrition, social decision making, and self-esteem training were provided. Participants…

  16. 21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person...

  17. Effects of anabolic agents on protein breakdown in L6 myoblasts.

    PubMed Central

    Ballard, F J; Francis, G L

    1983-01-01

    1. Protein degradation in rat L6 myoblasts is inhibited by high concentrations of insulin as well as by foetal bovine serum and bovine colostrum, mixtures rich in growth-factor activity. 2. Growth factors achieve maximal effects within 2 h after addition to the cell cultures, but these diminish with time. Indeed, during incubations greater than 12 h, foetal calf serum actually stimulates protein breakdown. The changed response, however, is not due to the depletion of growth factors from serum. 3. Protein breakdown is stimulated by dexamethasone by a process that takes several hours to be expressed, but is more pronounced over a 4 h measurement period than over 18h. The glucocorticoid response is prevented by insulin or by cycloheximide. 4. Anabolic agents such as trenbolone, diethylstilboestrol and testosterone do not alter rates of intracellular protein breakdown and do not interfere with the glucocorticoid-induced catabolic response. 5. The results are consistent with anabolic steroids and related agents acting indirectly on muscle, perhaps via altering concentrations of growth factors of the somatomedin type. PMID:6342615

  18. Understanding key factors of users' intentions to repurchase and recommend digital items in social virtual worlds.

    PubMed

    Kim, Byoungsoo

    2012-10-01

    Given to the remarkable profitability of digital items in social virtual worlds (SVWs), such as SecondLife, Cyworld, and Habbo Hotel, it has become crucial to understand SVW users' postadoption behaviors toward digital items. This study develops a theoretical framework to examine key antecedents of users' intentions to repurchase and recommend digital items. Data collected from 256 users of digital items were empirically tested against the research model. The analysis results indicate that both user satisfaction and a perceived value play an important role in establishing users' postadoption intentions about digital items. Moreover, the results clearly show what roles perceived usefulness, perceived enjoyment, and perceived fee play in SVW environments.

  19. Enhanced Production of Insulin-like Growth Factor I Protein in Escherichia coli by Optimization of Five Key Factors

    PubMed Central

    Ranjbari, Javad; Babaeipour, Valiollah; Vahidi, Hossein; Moghimi, Hamidreza; Mofid, Mohammad Reza; Namvaran, Mohammad Mehdi; Jafari, Sevda

    2015-01-01

    Human insulin-like growth factor I (hIGF-I) is a kind of growth factor with clinical significance in medicine. Up to now, E. coli expression system has been widely used as a host to produce rhIGF-1 with high yields. Batch cultures as non-continuous fermentations were carried out to overproduce rhIGF-I in E. coli. The major objective of this study is over- production of recombinant human insulin-like growth factor I (rhIGF-I) through a developed process by recruiting effective factors in order to achieve the most recombinant protein. In this study we investigated the effect of culture medium, induction temperature and amount of inducer on cell growth and IGF-1 production. Taguchi design of experiments (DOE) method was used as the statistical method. Analysis of experimental data showed that maximum production of rhIGF-I was occurred in 32y culture medium at 32 °C and 0.05 Mm IPTG. Under this condition, 0.694 g/L of rhIGF-I was produced as the inclusion bodies. Following optimization of these three factors, we have also optimized the amount of glucose and induction time in 5 liter top bench bioreactor. Full factorial design of experiment method was used for these two factors as the statistical method. 10 g/L and OD600=5 were selected as the optimum point of Glucose amount and induction time, respectively. Finally, we reached to a concentration of 1.26 g/L rhIGF-1 at optimum condition. PMID:26330880

  20. Belongingness in Early Secondary School: Key Factors that Primary and Secondary Schools Need to Consider

    PubMed Central

    Vaz, Sharmila; Falkmer, Marita; Ciccarelli, Marina; Passmore, Anne; Parsons, Richard; Black, Melissa; Cuomo, Belinda; Tan, Tele; Falkmer, Torbjörn

    2015-01-01

    It is unknown if, and how, students redefine their sense of school belongingness after negotiating the transition to secondary school. The current study used longitudinal data from 266 students with, and without, disabilities who negotiated the transition from 52 primary schools to 152 secondary schools. The study presents the 13 most significant personal student and contextual factors associated with belongingness in the first year of secondary school. Student perception of school belongingness was found to be stable across the transition. No variability in school belongingness due to gender, disability or household-socio-economic status (SES) was noted. Primary school belongingness accounted for 22% of the variability in secondary school belongingness. Several personal student factors (competence, coping skills) and school factors (low-level classroom task-goal orientation), which influenced belongingness in primary school, continued to influence belongingness in secondary school. In secondary school, effort-goal orientation of the student and perception of their school’s tolerance to disability were each associated with perception of school belongingness. Family factors did not influence belongingness in secondary school. Findings of the current study highlight the need for primary schools to foster belongingness among their students at an early age, and transfer students’ belongingness profiles as part of the hand-over documentation. Most of the factors that influenced school belongingness before and after the transition to secondary are amenable to change. PMID:26372554

  1. An acoustic key to eight languages/dialects: Factor analyses of critical-band-filtered speech

    PubMed Central

    Ueda, Kazuo; Nakajima, Yoshitaka

    2017-01-01

    The peripheral auditory system functions like a frequency analyser, often modelled as a bank of non-overlapping band-pass filters called critical bands; 20 bands are necessary for simulating frequency resolution of the ear within an ordinary frequency range of speech (up to 7,000 Hz). A far smaller number of filters seemed sufficient, however, to re-synthesise intelligible speech sentences with power fluctuations of the speech signals passing through them; nevertheless, the number and frequency ranges of the frequency bands for efficient speech communication are yet unknown. We derived four common frequency bands—covering approximately 50–540, 540–1,700, 1,700–3,300, and above 3,300 Hz—from factor analyses of spectral fluctuations in eight different spoken languages/dialects. The analyses robustly led to three factors common to all languages investigated—the low & mid-high factor related to the two separate frequency ranges of 50–540 and 1,700–3,300 Hz, the mid-low factor the range of 540–1,700 Hz, and the high factor the range above 3,300 Hz—in these different languages/dialects, suggesting a language universal. PMID:28198405

  2. An acoustic key to eight languages/dialects: Factor analyses of critical-band-filtered speech.

    PubMed

    Ueda, Kazuo; Nakajima, Yoshitaka

    2017-02-15

    The peripheral auditory system functions like a frequency analyser, often modelled as a bank of non-overlapping band-pass filters called critical bands; 20 bands are necessary for simulating frequency resolution of the ear within an ordinary frequency range of speech (up to 7,000 Hz). A far smaller number of filters seemed sufficient, however, to re-synthesise intelligible speech sentences with power fluctuations of the speech signals passing through them; nevertheless, the number and frequency ranges of the frequency bands for efficient speech communication are yet unknown. We derived four common frequency bands-covering approximately 50-540, 540-1,700, 1,700-3,300, and above 3,300 Hz-from factor analyses of spectral fluctuations in eight different spoken languages/dialects. The analyses robustly led to three factors common to all languages investigated-the low &mid-high factor related to the two separate frequency ranges of 50-540 and 1,700-3,300 Hz, the mid-low factor the range of 540-1,700 Hz, and the high factor the range above 3,300 Hz-in these different languages/dialects, suggesting a language universal.

  3. Binding Mode Analysis of Zerumbone to Key Signal Proteins in the Tumor Necrosis Factor Pathway

    PubMed Central

    Fatima, Ayesha; Abdul, Ahmad Bustamam Hj.; Abdullah, Rasedee; Karjiban, Roghayeh Abedi; Lee, Vannajan Sanghiran

    2015-01-01

    Breast cancer is the second most common cancer among women worldwide. Several signaling pathways have been implicated as causative and progression agents. The tumor necrosis factor (TNF) α protein plays a dual role in promoting and inhibiting cancer depending largely on the pathway initiated by the binding of the protein to its receptor. Zerumbone, an active constituent of Zingiber zerumbet, Smith, is known to act on the tumor necrosis factor pathway upregulating tumour necrosis factor related apoptosis inducing ligand (TRAIL) death receptors and inducing apoptosis in cancer cells. Zerumbone is a sesquiterpene that is able to penetrate into the hydrophobic pockets of proteins to exert its inhibiting activity with several proteins. We found a good binding with the tumor necrosis factor, kinase κB (IKKβ) and the Nuclear factor κB (NF-κB) component proteins along the TNF pathway. Our results suggest that zerumbone can exert its apoptotic activities by inhibiting the cytoplasmic proteins. It inhibits the IKKβ kinase that activates the NF-κB and also binds to the NF-κB complex in the TNF pathway. Blocking both proteins can lead to inhibition of cell proliferating proteins to be downregulated and possibly ultimate induction of apoptosis. PMID:25629232

  4. Initiation and maintenance of a hospital-based parent group for parents of premature infants: key factors for success.

    PubMed

    Bracht, M; Ardal, F; Bot, A; Cheng, C M

    1998-04-01

    The impact of a premature birth can be very traumatic for parents. They are usually not prepared for this event, and their sense of grief and loss is so intense that they often have difficulty coping with the situation. A parent group can help parents adapt to the crisis of prematurity by providing information and family support. This article describes the development of a parent group at a regional perinatal center in Ontario and identifies key factors for its successful initiation and maintenance.

  5. Identification of key factors regulating self-renewal and differentiation in EML hematopoietic precursor cells by RNA-sequencing analysis.

    PubMed

    Zong, Shan; Deng, Shuyun; Chen, Kenian; Wu, Jia Qian

    2014-11-11

    Hematopoietic stem cells (HSCs) are used clinically for transplantation treatment to rebuild a patient's hematopoietic system in many diseases such as leukemia and lymphoma. Elucidating the mechanisms controlling HSCs self-renewal and differentiation is important for application of HSCs for research and clinical uses. However, it is not possible to obtain large quantity of HSCs due to their inability to proliferate in vitro. To overcome this hurdle, we used a mouse bone marrow derived cell line, the EML (Erythroid, Myeloid, and Lymphocytic) cell line, as a model system for this study. RNA-sequencing (RNA-Seq) has been increasingly used to replace microarray for gene expression studies. We report here a detailed method of using RNA-Seq technology to investigate the potential key factors in regulation of EML cell self-renewal and differentiation. The protocol provided in this paper is divided into three parts. The first part explains how to culture EML cells and separate Lin-CD34+ and Lin-CD34- cells. The second part of the protocol offers detailed procedures for total RNA preparation and the subsequent library construction for high-throughput sequencing. The last part describes the method for RNA-Seq data analysis and explains how to use the data to identify differentially expressed transcription factors between Lin-CD34+ and Lin-CD34- cells. The most significantly differentially expressed transcription factors were identified to be the potential key regulators controlling EML cell self-renewal and differentiation. In the discussion section of this paper, we highlight the key steps for successful performance of this experiment. In summary, this paper offers a method of using RNA-Seq technology to identify potential regulators of self-renewal and differentiation in EML cells. The key factors identified are subjected to downstream functional analysis in vitro and in vivo.

  6. Vitamin D Receptor Deficiency and Low Vitamin D Diet Stimulate Aortic Calcification and Osteogenic Key Factor Expression in Mice

    PubMed Central

    Schmidt, Nadine; Brandsch, Corinna; Kühne, Hagen; Thiele, Alexandra; Hirche, Frank; Stangl, Gabriele I.

    2012-01-01

    Low levels of 25-hydroxy vitamin D (25(OH)D) are associated with cardiovascular diseases. Herein, we tested the hypothesis that vitamin D deficiency could be a causal factor in atherosclerotic vascular changes and vascular calcification. Aortic root sections of vitamin D receptor knockout (VDR−/−) mice that were stained for vascular calcification and immunostained for osteoblastic differentiation factors showed more calcified areas and a higher expression of the osteogenic key factors Msx2, Bmp2, and Runx2 than the wild-type mice (P<0.01). Data from LDL receptor knockout (LDLR−/−) mice that were fed western diet with either low (50 IU/kg), recommended (1,000 IU/kg), or high (10,000 IU/kg) amounts of vitamin D3 over 16 weeks revealed increasing plasma concentrations of 25(OH)D (P<0.001) with increasing intake of vitamin D, whereas levels of calcium and phosphorus in plasma and femur were not influenced by the dietary treatment. Mice treated with the low vitamin D diet had more calcified lesions and a higher expression of Msx2, Bmp2, and Runx2 in aortic roots than mice fed recommended or high amounts of vitamin D (P<0.001). Taken together, these findings indicate vitamin D deficiency as a risk factor for aortic valve and aortic vessel calcification and a stimulator of osteogenic key factor expression in these vascular areas. PMID:22536373

  7. Museum specimens reveal loss of pollen host plants as key factor driving wild bee decline in The Netherlands.

    PubMed

    Scheper, Jeroen; Reemer, Menno; van Kats, Ruud; Ozinga, Wim A; van der Linden, Giel T J; Schaminée, Joop H J; Siepel, Henk; Kleijn, David

    2014-12-09

    Evidence for declining populations of both wild and managed bees has raised concern about a potential global pollination crisis. Strategies to mitigate bee loss generally aim to enhance floral resources. However, we do not really know whether loss of preferred floral resources is the key driver of bee decline because accurate assessment of host plant preferences is difficult, particularly for species that have become rare. Here we examine whether population trends of wild bees in The Netherlands can be explained by trends in host plants, and how this relates to other factors such as climate change. We determined host plant preference of bee species using pollen loads on specimens in entomological collections that were collected before the onset of their decline, and used atlas data to quantify population trends of bee species and their host plants. We show that decline of preferred host plant species was one of two main factors associated with bee decline. Bee body size, the other main factor, was negatively related to population trend, which, because larger bee species have larger pollen requirements than smaller species, may also point toward food limitation as a key factor driving wild bee loss. Diet breadth and other potential factors such as length of flight period or climate change sensitivity were not important in explaining twentieth century bee population trends. These results highlight the species-specific nature of wild bee decline and indicate that mitigation strategies will only be effective if they target the specific host plants of declining species.

  8. Identifying the Key Factors Affecting the Chance of Passing Vocational Education and Training Subjects

    ERIC Educational Resources Information Center

    John, David

    2004-01-01

    This report identifies student characteristics--demographic and life-stage factors--which influence successful completion of vocational education and training (VET) subjects. It finds the likelihood of passing is significantly reduced for people who are Indigenous, have a disability, are of non-English speaking background, are unemployed or are…

  9. Students' Understanding of Large Numbers as a Key Factor in Their Understanding of Geologic Time

    ERIC Educational Resources Information Center

    Cheek, Kim A.

    2012-01-01

    An understanding of geologic time is comprised of 2 facets. Events in Earth's history can be placed in relative and absolute temporal succession on a vast timescale. Rates of geologic processes vary widely, and some occur over time periods well outside human experience. Several factors likely contribute to an understanding of geologic time, one of…

  10. On the Factor Structure of the Beck Depression Inventory-II: G Is the Key

    ERIC Educational Resources Information Center

    Brouwer, Danny; Meijer, Rob R.; Zevalkink, Jolien

    2013-01-01

    The Beck Depression Inventory-II (BDI-II; Beck, Steer, & Brown, 1996) is intended to measure severity of depression, and because items represent a broad range of depressive symptoms, some multidimensionality exists. In recent factor-analytic studies, there has been a debate about whether the BDI-II can be considered as one scale or whether…

  11. Key factors influencing canine heartworm, Dirofilaria immitis, in the United States

    PubMed Central

    2012-01-01

    An examination of the Companion Animal Parasite Council’s (CAPC) canine heartworm data to clarify the spatial prevalence of heartworm in the United States. Factors thought to influence the spatial risk of disease, as identified in a recent CAPC workshop, are discussed. PMID:23111089

  12. Key Factors in Smoking Cessation Intervention among 15-16-Year-Olds

    ERIC Educational Resources Information Center

    Heikkinen, Anna Maria; Broms, Ulla; Pitkaniemi, Janne; Koskenvuo, Markku; Meurman, Jukka

    2009-01-01

    The authors aimed to investigate factors associated with smoking cessation among adolescents after tobacco intervention. They examined smokers (n = 127) from one birth cohort (n = 545) in the city of Kotka in Finland. These smokers were randomized in 3 intervention groups the dentist (n = 44) and the school nurse (n = 42 groups), and a control…

  13. Transcriptome analyses identify key cellular factors associated with HIV-1 associated neuropathogenesis in infected men

    PubMed Central

    Venkatachari, Narasimhan J.; Jain, Siddhartha; Walker, Leah; Bivalkar-Mehla, Shalmali; Chattopadhyay, Ansuman; Bar-Joseph, Ziv; Rinaldo, Charles; Ragin, Ann; Seaberg, Eric; Levine, Andrew; Becker, James; Martin, Eileen; Sacktor, Ned; Ayyavoo, Velpandi

    2017-01-01

    Objective HIV-1 viral proteins and host inflammatory factors have a direct role in neuronal toxicity in in vitro, however, the contribution of these factors in vivo in HIV-1 associated neurocognitive disorder (HAND) is not fully understood. We applied novel Systems Biology approaches to identify specific cellular and viral factors and their related pathways that are associated with different stages of HAND. Design A cross-sectional study of individuals enrolled in the Multicenter AIDS Cohort Study (MACS) including HIV-1 seronegative (N=36) and HIV-1 seropositive individuals without neurocognitive symptoms (N=16), or with mild neurocognitive disorder (MND) (N=8) or HIV-associated dementia (HAD) (N=16). Methods A systematic evaluation of global transcriptome of peripheral blood mononuclear cells (PBMCs) obtained from HIV-1 seronegative individuals and from HIV-1 positive men without neurocognitive symptoms, or MND or HAD was performed. Results MND and HAD were associated with specific changes in mRNA transcripts and miRNAs in PBMCs. Comparison of upstream regulators and TimePath analyses identified specific cellular factors associated with MND and HAD, while HIV-1 viral proteins played a greater role in HAD. Additionally, expression of specific microRNAs – miR-let-7a, miR-124, miR-15a and others were found to correlate with mRNA gene expression and may have a potential protective role in asymptomatic HIV-1 seropositive individuals by regulating cellular signal transduction pathways downstream of chemokines and cytokines. Conclusions These results identify signature transcriptome changes in PBMCs associated with stages of HAND and shed light on the potential contribution of host cellular factors and viral proteins in HAND development. PMID:28005686

  14. Oxidative stress--a key emerging impact factor in health, ageing, lifestyle and aesthetics.

    PubMed

    Kandola, K; Bowman, A; Birch-Machin, M A

    2015-12-01

    Oxidative stress is the resultant damage that arises due to redox imbalances, more specifically an increase in destructive free radicals and reduction in protection from antioxidants and the antioxidant defence pathways. Oxidation of lipids by reactive oxygen species (ROS) can damage cellular structures and result in premature cell death. At low levels, ROS-induced oxidative stress can be prevented through the action of antioxidants, however, when ROS are present in excess, inflammation and cytotoxicity eventually results leading to cellular oxidative stress damage. Increasing evidence for the role of oxidative stress in various diseases including neurological, dermatological, and cardiovascular diseases is now emerging. Mitochondria are the principal source (90%) of ROS in the cell, with superoxide radicals being generated when molecular oxygen is combined with free electrons. Given the key role of mitochondria in the generation of cellular oxidative stress it is worth considering this organelle and the process in more detail and to provide methods of intervention.

  15. Key recovery factors for the August 24, 2014, South Napa earthquake

    USGS Publications Warehouse

    Hudnut, Kenneth W.; Brocher, Thomas M.; Prentice, Carol S.; Boatwright, John; Brooks, Benjamin A.; Aagaard, Brad T.; Blair, James Luke; Fletcher, Joe B.; Erdem, Jemile E.; Wicks, Charles W.; Murray, Jessica R.; Pollitz, Fred F.; Langbein, John O.; Svarc, Jerry L.; Schwartz, David P.; Ponti, Daniel J.; Hecker, Suzanne; DeLong, Stephen B.; Rosa, Carla M.; Jones, Brenda; Lamb, Rynn M.; Rosinski, Anne M.; McCrink, Timothy P.; Dawson, Timothy E.; Seitz, Gordon G.; Rubin, Ron S.; Glennie, Craig; Hauser, Darren; Ericksen, Todd; Mardock, Dan; Hoirup, Don F.; Bray, Jonathan D.

    2014-01-01

    Through discussions between the Federal Emergency Management Agency (FEMA) and the U.S. Geological Survey (USGS) following the South Napa earthquake, it was determined that several key decision points would be faced by FEMA for which additional information should be sought and provided by USGS and its partners. This report addresses the four tasks that were agreed to. These tasks are (1) assessment of ongoing fault movement (called afterslip) especially in the Browns Valley residential neighborhood, (2) assessment of the shaking pattern in the downtown area of the City of Napa, (3) improvement of information on the fault hazards posed by the West Napa Fault System (record of past earthquakes and slip rate, for example), and (4) imagery acquisition and data processing to provide overall geospatial information support to FEMA.

  16. Tissue factor and tissue factor pathway inhibitor as key regulators of global hemostasis: measurement of their levels in coagulation assays.

    PubMed

    Kasthuri, Raj S; Glover, Sam L; Boles, Jeremiah; Mackman, Nigel

    2010-10-01

    The tissue factor (TF)/factor (F)VIIa complex is the primary initiator of coagulation in vivo. Tissue factor pathway inhibitor (TFPI) is the physiological inhibitor of the TF/FVIIa complex. Deficiencies of either TF or TFPI have not been reported in humans, and a complete absence of either of these two proteins in mice is embryonically lethal. To maintain normal hemostasis, levels of TF and TFPI need to be balanced. Increased levels of TF can overwhelm the inhibitory capacity of TFPI, resulting in thrombosis. Decreased levels of TF are associated with bleeding. Global assays of coagulation are defined as tests capable of evaluating all components of the clotting cascade that are present in plasma. In these tests the thrombogenic surface is either provided by platelets or exogenous phospholipids. Clotting assays currently used in clinical practice are not designed to measure endogenous levels of TF and TFPI. Therefore, there is a need to develop sensitive and specific assays for measuring levels of functional TF and TFPI in whole blood and plasma. These assays could be useful in patient management in many scenarios.

  17. Key factors limiting the open circuit voltage of n(+)pp(+) indium phosphide solar cells

    NASA Technical Reports Server (NTRS)

    Goradia, Chandra; Thesling, William; Weinberg, Irving

    1991-01-01

    Solar cells made from gallium arsenide (GaAs), with a room temperature bandgap of E(sub g) = 1.43 eV have exhibited the best measured open circuit voltage (V sub OC) of 1.05 V at 1 AMO, 25 C. The material InP is in many ways similar to GaAs. A simple calculation comparing InP to GaAs then shows that solar cells made from InP, with E(sub g) = 1.35 at 300 K, should exhibit the best measured (V sub OC) of approximately 950 mV at 1 AMO, 300 K. However, to date, the best measured V(sub OC) for InP solar cells made by any fabrication method is 899 mV at AM1.5, 25 C which would translate to 912 mV at 1 AMO, 25 C. The V(sub OC) of an n(+)pp(+) InP solar cell is governed by several factors. Of these, some factors, such as the thickness and doping of the emitter and base regions, are easily controlled and can be adjusted to desired values dictated by a good performance optimizing model. Such factors were not considered. There are other factors which also govern V(sub OC), and their values are not so easily controlled. The primary ones among these are (1) the indirect or Hall-Shockley-Read lifetimes in the various regions of the cell, (2) the low-doping intrinsic carrier concentration n(sub i) of the InP material, (3) the heavy doping factors in the emitter and BSF regions, and (4) the front surface recombination velocity S(sub F). The influence of these latter factors on the V(sub OC) of the n(+)pp(+) InP solar cell and the results were used to produce a near-optimum design of the n(+)pp(+) InP solar cell.

  18. Key factors limiting the open circuit voltage of n(+)pp(+) indium phosphide solar cells

    NASA Technical Reports Server (NTRS)

    Goradia, Chandra; Thesling, William; Weinberg, Irving

    1990-01-01

    Solar cells made from gallium arsenide (Gaas), with a room temperature bandgap of E(sub g) = 1.43 eV have exhibited the best measured open circuit voltage (V sub oc) of 1.05 V at 1 AM0, 25 C. The material InP is in many ways similar to GaAs. A simple calculation comparing InP to GaAs then shows that solar cells made from InP, with E(sub g) = 1.35 at 300 K, should exhibit the best measured V sub oc of approximately 950 mV at 1 AM0, 300 K. However, to date, the best measured V sub oc for InP solar cells made by any fabrication method is 899 mV at AM1.5, 25 C which would translate to 912 mV at 1 AM0, 25 C. The V sub oc of an n(+)pp(+) InP solar cell is governed by several factors. Of these, some factors, such as the thickness and doping of the emitter and base regions, are easily controlled and can be adjusted to desired values dictated by a good performance optimizing model. Such factors were not considered. There are other factors which also govern V sub oc, and their values are not so easily controlled. The primary ones among these are (1) the indirect or Hall-Shockley-Read lifetimes in the various regions of the cell, (2) the low-doping intrinsic carrier concentration n(sub i) of the InP material, (3) the heavy doping factors in the emitter and BSF regions, and (4) the front surface recombination velocity S(sub F). The influence of these latter factors on the V sub oc of the n(+)pp(+) InP solar cell and the results were used to produce a near-optimum design of the n(+)pp(+) InP solar cell.

  19. Anabolic steroids, acute myocardial infarction and polycythemia: a case report and review of the literature.

    PubMed

    Stergiopoulos, Kathleen; Brennan, Joseph J; Mathews, Robin; Setaro, John F; Kort, Smadar

    2008-01-01

    The association between testosterone-replacement therapy and cardiovascular risk remains unclear with most reports suggesting a neutral or possibly beneficial effect of the hormone in men and women. However, several cardiovascular complications including hypertension, cardiomyopathy, stroke, pulmonary embolism, fatal and nonfatal arrhythmias, and myocardial infarction have been reported with supraphysiologic doses of anabolic steroids. We report a case of an acute ST-segment elevation myocardial infarction in a patient with traditional cardiac risk factors using supraphysiologic doses of supplemental, intramuscular testosterone. In addition, this patient also had polycythemia, likely secondary to high-dose testosterone. The patient underwent successful percutaneous intervention of the right coronary artery. Phlebotomy was used to treat the polycythemia acutely. We suggest that the chronic and recent "stacked" use of intramuscular testosterone as well as the resultant polycythemia and likely increased plasma viscosity may have been contributing factors to this cardiovascular event, in addition to traditional coronary risk factors. Physicians and patients should be aware of the clinical consequences of anabolic steroid abuse.

  20. Soil Surface Structure: A key factor for the degree of soil water repellency

    NASA Astrophysics Data System (ADS)

    Ahn, S.; Doerr, S. H.; Douglas, P.; Bryant, R.; Hamlett, C.; McHale, G.; Newton, M.; Shirtcliffe, N.

    2012-04-01

    Despite of considerable efforts, the degree of water repellency has not always been fully explained by chemical property of soil (termed hydrophobicity). That might be because the structure of a soil surface was not considered properly, which is another main factor determining the severity of soil water repellency. Surface structure has only recently been considered in soil science, whilst it has been paid attention for several decades in materials science due to its relevance to industrial applications. In this contribution, comparison of critical contact angles measured on different surface structures (made with glass beads, glass shards and beach sands) is presented and the effect of surface structure on manifestation of soil water repellency is discussed in terms of several different variables such as the individual particles shape, and areal and structural factors of the actual surface.

  1. Academic mobility as a key factor of quality assurance in tertiary education

    NASA Astrophysics Data System (ADS)

    Voroshilova, Anna A.

    2015-01-01

    Academic mobility of both faculty and students forms a critical element of the international dimension of higher education and is one of the most important factors of quality assurance of higher education institutions worldwide. Internationalization and globalization of Russian higher education system is having one of the major impacts on the quality management and assurance. Faculty and student mobility figures are now one of the core factors for obtaining state accreditation for Russian universities as well as an important indicator showing the university success and prestige. The aim of the paper is a closer look at the perspectives and results of the academic mobility, the factors stimulating and discouraging mobility, and the outcomes of the mobility influencing the education in Russian universities. Siberian State Aerospace University has had more than 10 years experience in organizing student mobility. Most of the problems in carrying out international activities are common for the whole Russia but still there are some peculiarities featuring technical universities situated in the centre of Russia.

  2. "Anabolic" effects of methandienone in men undergoing athletic training.

    PubMed

    Hervey, G R; Hutchinson, I; Knibbs, A V; Burkinshaw, L; Jones, P R; Norgan, N G; Levell, M J

    1976-10-02

    After failure to confirm an anabolic action of testosterone and its derivatives in rats, methandienone ('Dianabol', an "anabolic steroid" used by athletes) has been given to 11 athletic men during a course of weight-training, in a double-blind, crossover experiment. The dose of methandienone was 100 mg/day for 6 wk. Body weight and composition, muscular strength and performance, and indices of endocrine function were studied. Compared with the placebo period, on methandienone the subjects gained weight (mean 3-3 kg +/- 0-6 kg) and accumulated a disproportionately large amount of potassium (420+/-68 mmol); the increase in weight was confined to the lean part of the body, and the muscles increased in size. Strength and performance improved over each training period, but not significantly differently on drug and placebo. On the drug, plasma-cortisol concentration and urinary cortisol excretion increased, and plasma-testosterone decreased. Although the weight and body-composition changes may demonstrate an anabolic action of methandienone in man, they may alternatively have been caused by an increase in intracellular fluid, and the question of anabolic action therefore remains open.

  3. Investigation of anabolic steroids in two taste aversion paradigms.

    PubMed

    Ganesan, R; Rosellini, R A; Svare, B

    1993-02-01

    The aversive effects of estradiol have been studied in two different taste aversion paradigms. A similar investigation was undertaken for the anabolic-androgenic steroids, nandralone and testosterone cypionate, using Rockland-Swiss mice. Experiments 1 and 2 used the brief exposure of a novel saccharin solution as the conditioned stimulus for taste aversion learning, and showed that anabolic steroids (1 mg) do not induce taste aversions. Instead, these hormones induced a small non-contingent increase in saccharin preference. Experiment 3 showed that daily nandralone administration (1 mg/day) had a greater anabolic effect than the same dose of testosterone cypionate. Experiment 4 paired the continuous exposure to a novel diet with daily nandralone injections, and showed that steroid treatment increased intake of the novel diet. When the novel diet was subsequently presented with the familiar diet in a two-choice preference test, there was no indication that an aversion was conditioned to the novel target diet. On the contrary, nandralone treatment significantly increased the preference for the novel diet. These experiments show that anabolic-androgenic steroids do not have aversive effects in mice, and that they may have positive consequences.

  4. Bolus vs. continuous feeding to optimize anabolism in neonates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neonates with feeding difficulties can be fed by orogastric tube, using either continuous or bolus delivery. This review reports on recent findings that bolus is advantageous compared to continuous feeding in supporting optimal protein anabolism. Whether bolus or continuous feeding is more beneficia...

  5. Psychological and Behavioral Effects of Anabolic-Androgenic Steroids.

    ERIC Educational Resources Information Center

    Bahrke, Michael S.

    This review of the literature on the psychological and behavioral effects of anabolic-androgenic steroids (AS) first looks at aspects of the history and prevalence of AS use in competitive sports. Research suggests that one-quarter to one-half million adolescents in the United States have used, or are currently using AS. Some effects of androgens…

  6. Hypercholesterolemia in Male Power Lifters Using Anabolic-Androgenic Steroids.

    ERIC Educational Resources Information Center

    Cohen, Jonathan C.; And Others

    1988-01-01

    Measurement of serum cholesterol concentrations in male power lifters who used anabolic-androgenic steroids for eight weeks, three years, or eight years indicated that mean serum cholesterol levels increased with drug use, but decreased promptly to near pre-steroid levels after steroid use ended. (Author/CB)

  7. Project Right Way: An Anabolic Steroid Education Program.

    ERIC Educational Resources Information Center

    Nutter, June

    There is increasing concern by medical experts in this country about the use of anabolic steroids by teenagers. Over one million Americans are believed to be currently using or have used the synthetic hormones in the past. While drug testing and a reduction in the supply of the drugs appear to be reducing the number of adult users, use by…

  8. Anabolic Steroid Use: Indications of Habituation among Adolescents.

    ERIC Educational Resources Information Center

    Yesalis, Charles E.; And Others

    1989-01-01

    Identified characteristics of adolescent male anabolic steroid (AS) user and addictive potential. Found AS user population different from nonuser in self-perceptions of health and strength, interest in controlling AS use, and perception of peer AS use. Found subgroups with significantly different attitudes and/or behaviors. Suggests prevention…

  9. Psychological Predictors of Anabolic Steroid Use: An Exploratory Study.

    ERIC Educational Resources Information Center

    Schwerin, Michael J.; Corcoran, Kevin J.; LaFleur, Bonnie J.; Fisher, Leslee; Patterson, David; Olrich, Tracy

    1997-01-01

    Examined social physique anxiety, upper body esteem, social anxiety, and body dissatisfaction as possible predictors of anabolic steroid (AS) use. Results based on 185 AS-using bodybuilders and various control groups indicated that the upper body strength subscale of two measures, along with age, were significant predictors of AS use. (RJM)

  10. The Incidence of Anabolic Steroid Use among Competitive Bodybuilders.

    ERIC Educational Resources Information Center

    Tricker, Ray; And Others

    1989-01-01

    Investigated incidence of anabolic steroid use among 380 competitive male and female bodybuilders in Kansas and Missouri. Results indicated more than half (54 percent) of the male bodybuilders were using steroids on a regular basis compared to 10 percent of the female competitors. Found main reason for use of steroids was desire to win. (Author/TE)

  11. Key Factors and Timing Patterns in the Tennis Forehand of Different Skill Levels

    PubMed Central

    Landlinger, Johannes; Lindinger, Stefan; Stöggl, Thomas; Wagner, Herbert; Müller, Erich

    2010-01-01

    The main purpose of the present study was to quantify and compare selected kinematic variables and their timing during the tennis forehand of different skill levels. An eight-camera 400 Hz, Vicon motion analysis system recorded kinematic data of six ATP- professionals (elite) and seven high performance (HP) players when shots were played cross court and down the line. Timing of the maximum angles, linear and angular velocities was measured prior to and after impact. A total of twelve strokes per subject were analyzed from the beginning to the end of horizontal racquet movement. Significant differences (p < 0.01) and large effect sizes were observed between elite and HP players in the timing of maximum pelvis (-0.075 ± 0.008 vs. -0.093 ± 0.012 s) and trunk angular velocities (-0.057 ± 0.004 vs. -0.075 ± 0.011 s) before impact. The elite group showed a tendency (p < 0.05) towards higher peak horizontal shoulder (3.0 ± 0.4 vs. 2.5 ± 0.4 m·s-1) and racquet velocities (33.1 ± 2.4 vs. 31.1 ± 1.9 m·s-1) compared to the HP players. Depending on the situation (cross court vs. down the line), different peak hip, racquet and separation angles were found for both groups. Similar peak values were detected between groups for maximum angular velocities and displacement of key variables that had been selected for analysis. The findings of this study can be vital for successful player development, improved performance or injury prevention. The later occurrence of maximum angular pelvis and trunk rotations were the main reasons for the tendency towards higher horizontal shoulder and racquet velocities in the elite group. Key points Different timing of maximum angular pelvis and trunk rotations separated the elite from the high performance players. The elite group tended to reach higher horizontal shoulder and racquet velocities than the high performance group. In addition to maximum angular velocities, maximum racquet, shoulder, and hip alignment angles were similar

  12. Interferon regulatory factor 3 is a key regulation factor for inducing the expression of SAMHD1 in antiviral innate immunity

    PubMed Central

    Yang, Shen; Zhan, Yuan; Zhou, Yanjun; Jiang, Yifeng; Zheng, Xuchen; Yu, Lingxue; Tong, Wu; Gao, Fei; Li, Liwei; Huang, Qinfeng; Ma, Zhiyong; Tong, Guangzhi

    2016-01-01

    SAMHD1 is a type I interferon (IFN) inducible host innate immunity restriction factor that inhibits an early step of the viral life cycle. The underlying mechanisms of SAMHD1 transcriptional regulation remains elusive. Here, we report that inducing SAMHD1 upregulation is part of an early intrinsic immune response via TLR3 and RIG-I/MDA5 agonists that ultimately induce the nuclear translocation of the interferon regulation factor 3 (IRF3) protein. Further studies show that IRF3 plays a major role in upregulating endogenous SAMHD1 expression in a mechanism that is independent of the classical IFN-induced JAK-STAT pathway. Both overexpression and activation of IRF3 enhanced the SAMHD1 promoter luciferase activity, and activated IRF3 was necessary for upregulating SAMHD1 expression in a type I IFN cascade. We also show that the SAMHD1 promoter is a direct target of IRF3 and an IRF3 binding site is sufficient to render this promoter responsive to stimulation. Collectively, these findings indicate that upregulation of endogenous SAMHD1 expression is attributed to the phosphorylation and nuclear translocation of IRF3 and we suggest that type I IFN induction and induced SAMHD1 expression are coordinated. PMID:27411355

  13. Mathematical Model of Bone Remodeling Captures the Antiresorptive and Anabolic Actions of Various Therapies.

    PubMed

    Ross, David S; Mehta, Khamir; Cabal, Antonio

    2017-01-01

    A better understanding of the molecular pathways regulating the bone remodeling process should help in the development of new antiresorptive regulators and anabolic regulators, that is, regulators of bone resorption and of bone formation. Understanding the mechanisms by which parathyroid hormone (PTH) influences bone formation and how it switches from anabolic to catabolic action is important for treating osteoporosis (Poole and Reeve in Curr Opin Pharmacol 5:612-617, 2005). In this paper we describe a mathematical model of bone remodeling that incorporates, extends, and integrates several models of particular aspects of this biochemical system (Cabal et al. in J Bone Miner Res 28(8):1830-1836, 2013; Lemaire et al. in J Theor Biol 229:293-309, 2004; Peterson and Riggs in Bone 46:49-63, 2010; Raposo et al. in J Clin Endocrinol Metab 87(9):4330-4340, 2002; Ross et al. in J Disc Cont Dyn Sys Series B 17(6):2185-2200, 2012). We plan to use this model as a bone homeostasis platform to develop anabolic and antiresorptive compounds. The model will allow us to test hypotheses about the dynamics of compounds and to test the potential benefits of combination therapies. At the core of the model is the idealized account of osteoclast and osteoblast signaling given by Lemaire et al. (J Theor Biol 229:293-309, 2004). We have relaxed some of their assumptions about the roles of osteoprotegerin, transforming growth factor [Formula: see text], and receptor activator of nuclear factor [Formula: see text]B ligand; we have devised more detailed models of the interactions of these species. We have incorporated a model of the effect of calcium sensing receptor antagonists on remodeling (Cabal et al. in J Bone Miner Res 28(8):1830-1836, 2013). We have also incorporated a basic model of the effects of vitamin D on calcium homeostasis. We have included a simple model of the mechanism proposed by Bellido et al. (2003), Ross et al. (J Disc Cont Dyn Sys Series B 17(6):2185-2200, 2012), of the

  14. Crystallographic orientation and electrode nature are key factors for electric current generation by Geobacter sulfurreducens.

    PubMed

    Maestro, Beatriz; Ortiz, Juan M; Schrott, Germán; Busalmen, Juan P; Climent, Víctor; Feliu, Juan M

    2014-08-01

    We have investigated the influence of electrode material and crystallographic structure on electron transfer and biofilm formation of Geobacter sulfurreducens. Single-crystal gold-Au(110), Au(111), Au(210)-and platinum-Pt(100), Pt(110), Pt(111), Pt(210)-electrodes were tested and compared to graphite rods. G. sulfurreducens electrochemically interacts with all these materials with different attachment kinetics and final current production, although redox species involved in the electron transfer to the anode are virtually the same in all cases. Initial bacterial colonization was fastest on graphite up to the monolayer level, whereas gold electrodes led to higher final current densities. Crystal geometry was shown to have an important influence, with Au(210) sustaining a current density of up to 1442±101μAcm(-2) at the steady state, over Au(111) with 961±94μAcm(-2) and Au(110) with 944±89μAcm(-2). On the other hand, the platinum electrodes displayed the lowest performances, including Pt(210). Our results indicate that both crystal geometry and electrode material are key parameters for the efficient interaction of bacteria with the substrate and should be considered for the design of novel materials and microbial devices to optimize energy production.

  15. Key factors in imprecision in radiological emergency response assessments using the NAME model.

    PubMed

    Haywood, S M; Bedwell, P; Hort, M C

    2010-03-01

    In the very early stages of response to an accidental release of radioactivity leading to environmental contamination, it is likely that only limited measurements of radioactivity in the local environment will be available on which to base decisions concerning protection measures and radiation monitoring activities. Model predictions will be used to aid understanding of the radiological situation and to form a basis for emergency health protection decisions. This paper presents an analysis of the relative importance of contributors to the imprecision associated with emergency response calculations based on a few off-site measurements, using predictions from the UK Met Office's NAME III (Numerical Atmospheric dispersion Modelling Environment version 5.2) dispersion model. The results presented extend those from a previous study in which a simple Gaussian plume model was used and confirm the key parameters contributing to imprecision. The potential extent of the sheltering countermeasure resulting from a hypothetical release in real weather conditions occurring in 2007 and 2008 is also presented.

  16. Key Factors Influencing Rates of Heterotrophic Sulfate Reduction in Hydrothermal Massive Sulfide Deposits

    NASA Astrophysics Data System (ADS)

    Frank, K. L.; Rogers, K. L.; Rogers, D.; Johnston, D. T.; Girguis, P. R.

    2015-12-01

    Hydrothermal vents are thermally and geochemically dynamic habitats, and the organisms therein are subject to steep fluctuations in temperature and chemistry. To date, the influence of these environmental dynamics on microbial sulfate reduction has not been well constrained. Here, via multivariate experiments, we evaluate the effects of key environmental variables (temperature, pH, H2S, SO42-, DOC) on sulfate reduction rates and metabolic energy yields in a hydrothermal flange recovered from the Grotto vent in the Main Endeavor Field, Juan de Fuca ridge. Sulfate reduction was measured in batch reactions across a range of physico-chemical conditions. Temperature and pH were the strongest stimuli and maximum sulfate reduction rates were observed at 50°C and pH 6, suggesting that the in situ community of sulfate reducing organisms at Grotto may be most active in a slightly acidic and moderate thermal/chemical regime. At pH 4, sulfate reduction rates increased with sulfide concentrations most likely due to the mitigation of metal toxicity. While substrate concentrations also influenced sulfate reduction rates, energy-rich conditions muted the effect of metabolic energetics on sulfate reduction rates. We posit that variability in sulfate reduction rates reflect the response of the active microbial consortia to environmental constraints on in situ microbial physiology, toxicity, and the type and extent of energy limitation. These experiments help to constrain models of the spatial contribution of heterotrophic sulfate within the complex gradients inherent to hydrothermal deposits.

  17. Evaluation of thermal steam-explosion key operation factors to optimize biogas production from biological sludge.

    PubMed

    Pérez-Elvira, S I; Sapkaite, I; Fdz-Polanco, F

    2015-01-01

    Thermal steam-explosion is the most extended hydrolysis pretreatment to enhance anaerobic digestion of sludge. Thermal hydrolysis key parameters are temperature (T) and time (t), and the generally accepted values reported from full-scale information are: 150-230 °C and 20-60 min. This study assesses the influence of different temperature-time-flash combinations (110-180 °C, 5-60 min, 1-3 re-flashing) on the anaerobic degradation of secondary sludge through biochemical methane potential (BMP) tests. All the conditions tested presented higher methane production compared to the untreated sludge, and both solubilization (after the hydrolysis) and degradation (by anaerobic digestion) increased linearly when increasing the severity (T-t) of the pretreatment, reaching 40% solubilization and degradation of the particulate matter at 180° C-60 min. However, for the 180 °C temperature, the treatment time impacted negatively on the lag phase. No influence of re-flashing the pretreated matter was observed. In conclusion, thermal steam-explosion at short operation times (5 min) and moderate temperatures (145 °C) seems to be very attractive from a degradation point of view thus presenting a methane production enhancement similar to the one obtained at 180°C and without negative influence of the lag phase.

  18. Use of simulink to address key factors for radon mitigation in a Fairbanks home.

    PubMed

    Marsik, Tom; Johnson, Ron

    2008-05-01

    Hilly areas around Fairbanks, Alaska, are known to have elevated soil radon concentrations. Due to geological conditions, cold winters, and the resulting stack effect, houses in these areas are prone to higher indoor radon concentrations. Key variables with respect to radon mitigation were addressed in this paper by using a dynamic model implemented in MATLAB Simulink. These variables included the ventilation rate; the foundation flow resistance, which can be affected by sealing the foundation during the construction of a house; and the differential pressure between the subslab and the house interior, which can be affected by using a subslab depressurization system. The model was used for the scenario of a varying differential pressure and then for the scenario of a varying ventilation rate at a Fairbanks home where real-time radon concentrations were measured. The correlation coefficients between the model-predicted and measured radon concentrations were 0.96 and 0.94, for both scenarios respectively, which verified the feasibility of the model for predicting indoor radon concentrations.

  19. Mechanisms of surgical control of type 2 diabetes: GLP-1 is key factor.

    PubMed

    Holst, Jens Juul; Madsbad, Sten

    2016-07-01

    GLP-1 secretion in response to meals is dramatically increased after gastric bypass operations. GLP-1 is a powerful insulinotropic and anorectic hormone, and analogs of GLP-1 are widely used for the treatment of diabetes and recently approved also for obesity treatment. It is, therefore, reasonable to assume that the exaggerated GLP-1 secretion contributes to the antidiabetic and anorectic effects of gastric bypass. Indeed, human experiments with the GLP-1 receptor antagonist, Exendin 9-39, have shown that the improved insulin secretion, which is responsible for part of the antidiabetic effect of the operation, is reduced and or abolished after GLP-1 receptor blockade. Also the postoperative improvement of glucose tolerance is eliminated and or reduced by the antagonist, pointing to a key role for the exaggerated GLP-1 secretion. Indeed, there is evidence that the exaggerated GLP-1 secretion is also responsible for postprandial hypoglycemia sometimes observed after bypass. Other operations (biliopancreatic-diversion and or sleeve gastrectomy) appear to involve different and/or additional mechanisms, and so does experimental bariatric surgery in rodents. However, unlike bypass surgery in humans, the rodent operations are generally associated with increased energy metabolism pointing to an entirely different mechanism of action in the animals.

  20. Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities. Applied modifications in the steroidal structure.

    PubMed

    Fragkaki, A G; Angelis, Y S; Koupparis, M; Tsantili-Kakoulidou, A; Kokotos, G; Georgakopoulos, C

    2009-02-01

    Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone introduced for therapeutic purposes providing enhanced anabolic potency with reduced androgenic effects. Androgens mediate their action through their binding to the androgen receptor (AR) which is mainly expressed in androgen target tissues, such as the prostate, skeletal muscle, liver and central nervous system. This paper reviews some of the wide spectrum of testosterone and synthetic AAS structure modifications related to the intended enhancement in anabolic activity. The structural features of steroids necessary for effective binding to the AR and those which contribute to the stipulation of the androgenic and anabolic activities are also presented.

  1. The growth factor myostatin, a key regulator in skeletal muscle growth and homeostasis.

    PubMed

    Matsakas, A; Diel, P

    2005-03-01

    Skeletal muscle possesses the ability to both respond and adapt to changing environmental stimuli, leading to a set of metabolic and morphological adaptations, which allow it to better meet the energy demands of sustained physical activity. Great progress has been achieved over the past years by means of innovative molecular techniques, which has led to the discovery of new growth factors and the identification of molecular mechanisms involved in the regulation of muscle development. These findings provide new starting points to understand the molecular mechanisms involved in the adaptation of skeletal muscle to exercise training. One of these new identified growth factors is myostatin, a member of the transforming growth factor-beta family of proteins that has been demonstrated to play a fundamental role in the regulation of skeletal muscle growth during embryogenesis. Blocking of the myostatin signalling transduction pathway by specific inhibitors and genetic manipulations has been shown to result in a dramatic increase of skeletal muscle mass. This review focuses on the importance of myostatin in mediating skeletal muscle homeostasis in response to training as well as during the progress of myogenic disease, like atrophy or dystrophy. Manipulations of myostatin signalling may be useful for agriculture applications, treatment of muscle diseases, inhibition of muscle atrophy and last but not least as life style drugs in antiaging therapies or manipulations of the muscle to fat ratio. Drugs with the ability to modulate myostatin signalling may have the potential to enhance physical performance in athletes and therefore they probably represent a new class of doping substances.

  2. Youth-Adult Connectedness:: A Key Protective Factor for Adolescent Health.

    PubMed

    Sieving, Renee E; McRee, Annie-Laurie; McMorris, Barbara J; Shlafer, Rebecca J; Gower, Amy L; Kapa, Hillary M; Beckman, Kara J; Doty, Jennifer L; Plowman, Shari L; Resnick, Michael D

    2017-03-01

    Over the past 30 years, prevention science in the adolescent health field has moved from interventions focused on preventing single problem behaviors to efforts employing a dual approach, addressing risk factors that predict problems while simultaneously nurturing protective factors and promoting positive development. Through an examination of previous research and empirical case examples with vulnerable youth, this article considers the hypothesis that adolescents' sense of connectedness to caring adults acts as a protective factor against a range of risk behaviors. Multivariate analyses with existing data examined indicators of youth-adult connectedness among two groups at high risk for poor health outcomes: (1) mentor-youth relationship quality in an urban, ethnically diverse sample of students in a school-based mentoring program (2014 survey, N=239); and (2) parent-youth connectedness in a statewide sample of high school students who reported homelessness in the past year (2013 survey, N=3,627). For youth in the mentoring program, a high-quality youth-mentor relationship was significantly associated with positive social, academic, and health-related behaviors. Among students who experienced homelessness, all measures of parent connectedness were significantly associated with lower sexual risk levels. Collectively, findings from these analyses and previously published studies by this research group provide evidence that strong, positive relationships with parents and other caring adults protect adolescents from a range of poor health-related outcomes and promote positive development. Youth-adult connectedness appears to be foundational for adolescent health and well-being. Program, practice, and policy decisions should consider what strengthens or hinders caring, connected youth-adult relationships.

  3. Macrophage Migration Inhibitory Factor (MIF): A Key Player in Protozoan Infections

    PubMed Central

    de Dios Rosado, Juan; Rodriguez-Sosa, Miriam

    2011-01-01

    Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine produced by the pituitary gland and multiple cell types, including macrophages (Mø), dendritic cells (DC) and T-cells. Upon releases MIF modulates the expression of several inflammatory molecules, such as TNF-α, nitric oxide and cyclooxygenase 2 (COX-2). These important MIF characteristics have prompted investigators to study its role in parasite infections. Several reports have demonstrated that MIF plays either a protective or deleterious role in the immune response to different pathogens. Here, we review the role of MIF in the host defense response to some important protozoan infections. PMID:22110378

  4. Environments, risk and health harms: a qualitative investigation into the illicit use of anabolic steroids among people using harm reduction services in the UK

    PubMed Central

    Kimergård, Andreas; McVeigh, Jim

    2014-01-01

    Objectives The illicit use of anabolic steroids among the gym population continues to rise, along with the number of steroid using clients attending harm reduction services in the UK. This presents serious challenges to public health. Study objectives were to account for the experiences of anabolic steroid users and investigate how ‘risk environments’ produce harm. Methods Qualitative face-to-face interviews with 24 users of anabolic steroids engaged with harm reduction services in the UK. Results Body satisfaction was an important factor when deciding to start the use of anabolic steroids. Many users were unaware of the potential dangers of using drugs from the illicit market, whereas some had adopted a range of strategies to negotiate the hazards relating to the use of adulterated products, including self-experimentation to gauge the perceived efficacy and unwanted effects of these drugs. Viewpoints, first-hand anecdotes, norms and practices among groups of steroid users created boundaries of ‘sensible’ drug use, but also promoted practices that may increase the chance of harms occurring. Established users encouraged young users to go to harm reduction services but, at the same time, promoted risky injecting practices in the belief that this would enhance the efficacy of anabolic steroids. Conclusions Current steroid-related viewpoints and practices contribute to the risk environment surrounding the use of these drugs and may undermine the goal of current public health strategies including harm reduction interventions. The level of harms among anabolic steroid users are determined by multiple and intertwining factors, in addition to the harms caused by the pharmacological action or injury and illness associated with incorrect injecting techniques. PMID:24898090

  5. Development of Focal Segmental Glomerulosclerosis after Anabolic Steroid Abuse

    PubMed Central

    Herlitz, Leal C.; Markowitz, Glen S.; Farris, Alton B.; Schwimmer, Joshua A.; Stokes, Michael B.; Kunis, Cheryl; Colvin, Robert B.

    2010-01-01

    Anabolic steroid abuse adversely affects the endocrine system, blood lipids, and the liver, but renal injury has not been described. We identified an association of focal segmental glomerulosclerosis (FSGS) and proteinuria in a cohort of 10 bodybuilders (six white and four Hispanic; mean body mass index 34.7) after long-term abuse of anabolic steroids. The clinical presentation included proteinuria (mean 10.1 g/d; range 1.3 to 26.3 g/d) and renal insufficiency (mean serum creatinine 3.0 mg/dl; range 1.3 to 7.8 mg/dl); three (30%) patients presented with nephrotic syndrome. Renal biopsy revealed FSGS in nine patients, four of whom also had glomerulomegaly, and glomerulomegaly alone in one patient. Three biopsies revealed collapsing lesions of FSGS, four had perihilar lesions, and seven showed ≥40% tubular atrophy and interstitial fibrosis. Among eight patients with mean follow-up of 2.2 yr, one progressed to ESRD, the other seven received renin-angiotensin system blockade, and one also received corticosteroids. All seven patients discontinued anabolic steroids, leading to weight loss, stabilization or improvement in serum creatinine, and a reduction in proteinuria. One patient resumed anabolic steroid abuse and suffered relapse of proteinuria and renal insufficiency. We hypothesize that secondary FSGS results from a combination of postadaptive glomerular changes driven by increased lean body mass and potential direct nephrotoxic effects of anabolic steroids. Because of the expected rise in serum creatinine as a result of increased muscle mass in bodybuilders, this complication is likely underrecognized. PMID:19917783

  6. Development of focal segmental glomerulosclerosis after anabolic steroid abuse.

    PubMed

    Herlitz, Leal C; Markowitz, Glen S; Farris, Alton B; Schwimmer, Joshua A; Stokes, Michael B; Kunis, Cheryl; Colvin, Robert B; D'Agati, Vivette D

    2010-01-01

    Anabolic steroid abuse adversely affects the endocrine system, blood lipids, and the liver, but renal injury has not been described. We identified an association of focal segmental glomerulosclerosis (FSGS) and proteinuria in a cohort of 10 bodybuilders (six white and four Hispanic; mean body mass index 34.7) after long-term abuse of anabolic steroids. The clinical presentation included proteinuria (mean 10.1 g/d; range 1.3 to 26.3 g/d) and renal insufficiency (mean serum creatinine 3.0 mg/dl; range 1.3 to 7.8 mg/dl); three (30%) patients presented with nephrotic syndrome. Renal biopsy revealed FSGS in nine patients, four of whom also had glomerulomegaly, and glomerulomegaly alone in one patient. Three biopsies revealed collapsing lesions of FSGS, four had perihilar lesions, and seven showed > or =40% tubular atrophy and interstitial fibrosis. Among eight patients with mean follow-up of 2.2 yr, one progressed to ESRD, the other seven received renin-angiotensin system blockade, and one also received corticosteroids. All seven patients discontinued anabolic steroids, leading to weight loss, stabilization or improvement in serum creatinine, and a reduction in proteinuria. One patient resumed anabolic steroid abuse and suffered relapse of proteinuria and renal insufficiency. We hypothesize that secondary FSGS results from a combination of postadaptive glomerular changes driven by increased lean body mass and potential direct nephrotoxic effects of anabolic steroids. Because of the expected rise in serum creatinine as a result of increased muscle mass in bodybuilders, this complication is likely underrecognized.

  7. Developing Talented Soccer Players: An Analysis of Socio-Spatial Factors as Possible Key Constraints.

    PubMed

    Serra-Olivares, Jaime; Pastor-Vicedo, Juan C; González-Víllora, Sixto; Teoldo da Costa, Israel

    2016-12-01

    Most studies on the identification and development of soccer talent have been one-dimensional in nature. Although some multi-dimensional analyses have been conducted, few research studies have assessed in any depth the socio-spatial factors influencing talent development. The aim of this particular study was to analyse variations in the international representation of clubs (n = 821) and countries (n = 59) in the development of players who took part in the 2014 FIFA Soccer World Cup. Clubs and countries were ranked and divided into quartiles according to the number of players developed between the ages of 15 and 21 (clubs and countries that developed players for at least three years between these ages) and the number of official league matches played by these players up to the age of 23. Significant variations were observed between clubs in terms of the number of developed players who took part in the World Cup and the number of official league matches played by these players up to the age of 23 (p < .05), and also between countries (p < .05). The findings reveal the need to carry out more in-depth studies into the type of training and competition engaged in by elite players in the period of development between the ages of 15 and 21. It may be the case that these factors are potentially decisive socio-spatial constraints in the development of soccer talent.

  8. Developing Talented Soccer Players: An Analysis of Socio-Spatial Factors as Possible Key Constraints

    PubMed Central

    Pastor-Vicedo, Juan C.; González-Víllora, Sixto; Teoldo da Costa, Israel

    2016-01-01

    Abstract Most studies on the identification and development of soccer talent have been one-dimensional in nature. Although some multi-dimensional analyses have been conducted, few research studies have assessed in any depth the socio-spatial factors influencing talent development. The aim of this particular study was to analyse variations in the international representation of clubs (n = 821) and countries (n = 59) in the development of players who took part in the 2014 FIFA Soccer World Cup. Clubs and countries were ranked and divided into quartiles according to the number of players developed between the ages of 15 and 21 (clubs and countries that developed players for at least three years between these ages) and the number of official league matches played by these players up to the age of 23. Significant variations were observed between clubs in terms of the number of developed players who took part in the World Cup and the number of official league matches played by these players up to the age of 23 (p < .05), and also between countries (p < .05). The findings reveal the need to carry out more in-depth studies into the type of training and competition engaged in by elite players in the period of development between the ages of 15 and 21. It may be the case that these factors are potentially decisive socio-spatial constraints in the development of soccer talent. PMID:28031773

  9. On the key factors of angular correlations in complex-forming elementary reactions

    NASA Astrophysics Data System (ADS)

    Bonnet, L.; Rayez, J. C.

    2006-04-01

    In the mid-seventies, Case and Herschbach argued that for complex-forming three-atom reactions governed by long-range forces and performed in supersonic molecular beam experiments, vectorial properties are determined by a single parameter Λ' = , L' and j' being respectively the moduli of the orbital and rotational angular momenta of the products. A simple mathematical relation between vectorial properties and Λ' was then proposed. However, Λ' must be determined beforehand by phase space theory calculations. Besides, we have recently shown that scalar properties are mainly controled by two factors ρ'1 and ρ'2 respectively called angular excitation and diatomic inertial contribution. We show here that these factors control also vectorial properties. Moreover, the way they control them is summarized in a set of four figures. The advantage of our method is that ρ'1 and ρ'2 are related to the mechanical parameters of the reaction by very simple formulas, contrary to Λ'. Last by not least, our parameters appear to be mostly independent, so that vectorial properties cannot be said to strictly depend on Λ'. Nevertheless, it turns out that the rule proposed by Case and Herschbach is reasonable in many realistic situations.

  10. Identifying key factors in homeowner's adoption of water quality best management practices.

    PubMed

    Brehm, Joan M; Pasko, Danielle K; Eisenhauer, Brian W

    2013-07-01

    The recognition of the significance of the residential environment in contributing to non-point source (NPS) pollution and the inherently dispersed nature of NPS pollution itself that presents significant challenges to effective regulation has led to the creation and dissemination of best management practices (BMPs) that can reduce the impacts of NPS pollution (Environmental Protection Agency US, Protecting water quality from urban runoff, http://www.epa.gov/npdes/pubs/nps_urban-facts_final.pdf , 2003). However, very few studies have examined the factors that influence the adoption of BMPs by residential homeowners, despite the fact that residential environments have been identified as one of the most significant contributors to NPS pollution. Given this need, the purpose of this project was to explore how demographic and knowledge-based factors predict adoption of residential BMPs in an urbanizing watershed in Northern Illinois using statistical analyses of survey data collected as part of a watershed planning process. The findings indicate that broad knowledge of BMPs is the strongest predictor of use for a specific BMP. Knowledge of BMPs is strongly correlated with their use, which reinforces the need for educational programs, even among those assumed to be knowledgeable about BMPs.

  11. ACOG Committee Opinion No. 484: Performance enhancing anabolic steroid abuse in women.

    PubMed

    2011-04-01

    Anabolic steroids are composed of testosterone and other substances related to testosterone that promote growth of skeletal muscle, increase hemoglobin concentration, and mediate secondary sexual characteristics. These substances have been in use since the 1930s to promote muscle growth, improve athletic performance, and enhance cosmetic appearance. Although anabolic steroids are controlled substances, only to be prescribed by a physician, it is currently possible to obtain anabolic steroids illegally without a prescription. There are significant negative physical and psychologic effects of anabolic steroid use, which in women can cause significant cosmetic and reproductive changes. Anabolic steroid use can be addictive and, therefore, difficult to stop. Treatment for anabolic steroid abuse generally involves education, counseling, and management of withdrawal symptoms. Health care providers are encouraged to address the use of these substances, encourage cessation, and refer patients to substance abuse treatment centers to prevent the long-term irreversible consequences of anabolic steroid use.

  12. Are Osteoclasts Needed for the Bone Anabolic Response to Parathyroid Hormone?

    PubMed Central

    Pierroz, Dominique D.; Bonnet, Nicolas; Baldock, Paul A.; Ominsky, Michael S.; Stolina, Marina; Kostenuik, Paul J.; Ferrari, Serge L.

    2010-01-01

    PTH stimulates osteoblastic cells to form new bone and to produce osteoblast-osteoclast coupling factors such as RANKL. Whether osteoclasts or their activity are needed for PTH anabolism remains uncertain. We treated ovariectomized huRANKL knock-in mice with a human RANKL inhibitor denosumab (DMAb), alendronate (Aln), or vehicle for 4 weeks, followed by co-treatment with intermittent PTH for 4 weeks. Loss of bone mass and microarchitecture was prevented by Aln and further significantly improved by DMAb. PTH improved bone mass, microstructure, and strength, and was additive to Aln but not to DMAb. Aln inhibited biochemical and histomorphometrical indices of bone turnover, -i.e. osteocalcin and bone formation rate (BFR) on cancellous bone surfaces-, and Dmab inhibited them further. However Aln increased whereas Dmab suppressed osteoclast number and surfaces. PTH significantly increased osteocalcin and bone formation indices, in the absence or presence of either antiresorptive, although BFR remained lower in presence of Dmab. To further evaluate PTH effects in the complete absence of osteoclasts, high dose PTH was administered to RANK−/− mice. PTH increased osteocalcin similarly in RANK−/− and WT mice. It also increased BMD in RANK−/− mice, although less than in WT. These results further indicate that osteoclasts are not strictly required for PTH anabolism, which presumably still occurs via stimulation of modeling-based bone formation. However the magnitude of PTH anabolic effects on the skeleton, in particular its additive effects with antiresorptives, depends on the extent of the remodeling space, as determined by the number and activity of osteoclasts on bone surfaces. PMID:20558734

  13. Key Factors Influencing Rates of Heterotrophic Sulfate Reduction in Active Seafloor Hydrothermal Massive Sulfide Deposits

    PubMed Central

    Frank, Kiana L.; Rogers, Karyn L.; Rogers, Daniel R.; Johnston, David T.; Girguis, Peter R.

    2015-01-01

    Hydrothermal vents are thermally and geochemically dynamic habitats, and the organisms therein are subject to steep gradients in temperature and chemistry. To date, the influence of these environmental dynamics on microbial sulfate reduction has not been well constrained. Here, via multivariate experiments, we evaluate the effects of key environmental variables (temperature, pH, H2S, SO42−, DOC) on sulfate reduction rates and metabolic energy yields in material recovered from a hydrothermal flange from the Grotto edifice in the Main Endeavor Field, Juan de Fuca Ridge. Sulfate reduction was measured in batch reactions across a range of physico-chemical conditions. Temperature and pH were the strongest stimuli, and maximum sulfate reduction rates were observed at 50°C and pH 6, suggesting that the in situ community of sulfate-reducing organisms in Grotto flanges may be most active in a slightly acidic and moderate thermal/chemical regime. At pH 4, sulfate reduction rates increased with sulfide concentrations most likely due to the mitigation of metal toxicity. While substrate concentrations also influenced sulfate reduction rates, energy-rich conditions muted the effect of metabolic energetics on sulfate reduction rates. We posit that variability in sulfate reduction rates reflect the response of the active microbial consortia to environmental constraints on in situ microbial physiology, toxicity, and the type and extent of energy limitation. These experiments help to constrain models of the spatial contribution of heterotrophic sulfate reduction within the complex gradients inherent to seafloor hydrothermal deposits. PMID:26733984

  14. Maternal effects and range expansion: a key factor in a dynamic process?

    PubMed Central

    Duckworth, Renée A.

    2009-01-01

    generated in newly colonized populations. More generally, these results suggest that, as a key source of variation in colonizing phenotypes, maternal effects are of crucial importance for understanding the dynamics of range expansion. PMID:19324612

  15. KEY FACTORS THAT INFLUENCE THE PERFORMANCE PROPERTIES OF ARP/MCU SALTSTONE MIXES

    SciTech Connect

    Harbour, J.; Edwards, T.; Williams, V.

    2009-10-05

    At the Saltstone Production Facility (SPF), decontaminated salt solution (DSS) is combined with premix (a cementitious mixture of portland cement (PC), blast furnace slag (BFS) and Class F fly ash (FA)) in a Readco mixer to produce fresh (uncured) Saltstone. After transfer to the Saltstone Disposal Facility (SDF) the hydration reactions initiated during the contact of the premix and salt solution continue during the curing period to produce the hardened waste form product. The amount of heat generated from hydration and the resultant temperature increase in the vaults depend on the composition of the decontaminated salt solution being dispositioned as well as the grout formulation (mix design). This report details the results from Task 3 of the Saltstone Variability Study for FY09 which was performed to identify, and quantify when possible, those factors that drive the performance properties of the projected ARP/MCU Batches. A baseline ARP/MCU mix (at 0.60 water to cementitious materials (w/cm) ratio) was established and consisted of the normal premix composition and a salt solution that was an average of the projected compositions of the last three ARP/MCU batches developed by T. A. Le. This task introduced significant variation in (1) wt % slag, w/cm ratio, and wt % portland cement about the baseline mix and (2) the temperature of curing in order to better assess the dependence of the performance properties on these factors. Two separate campaigns, designated Phase 10 and Phase 11, were carried out under Task 3. Experimental designs and statistical analyses were used to search for correlation among properties and to develop linear models to predict property values based on factors such as w/cm ratio, slag concentration, and portland cement concentration. It turns out that the projected salt compositions contained relatively high amounts of aluminate (0.22 M) even though no aluminate was introduced due to caustic aluminate removal from High Level Waste. Previous

  16. Syntactic Computation in the Human Brain: The Degree of Merger as a Key Factor

    PubMed Central

    Ohta, Shinri; Fukui, Naoki; Sakai, Kuniyoshi L.

    2013-01-01

    Our goal of this study is to characterize the functions of language areas in most precise terms. Previous neuroimaging studies have reported that more complex sentences elicit larger activations in the left inferior frontal gyrus (L. F3op/F3t), although the most critical factor still remains to be identified. We hypothesize that pseudowords with grammatical particles and morphosyntactic information alone impose a construction of syntactic structures, just like normal sentences, and that “the Degree of Merger” (DoM) in recursively merged sentences parametrically modulates neural activations. Using jabberwocky sentences with distinct constructions, we fitted various parametric models of syntactic, other linguistic, and nonlinguistic factors to activations measured with functional magnetic resonance imaging. We demonstrated that the models of DoM and “DoM+number of Search (searching syntactic features)” were the best to explain activations in the L. F3op/F3t and supramarginal gyrus (L. SMG), respectively. We further introduced letter strings, which had neither lexical associations nor grammatical particles, but retained both matching orders and symbol orders of sentences. By directly contrasting jabberwocky sentences with letter strings, localized activations in L. F3op/F3t and L. SMG were indeed independent of matching orders and symbol orders. Moreover, by using dynamic causal modeling, we found that the model with a inhibitory modulatory effect for the bottom-up connectivity from L. SMG to L. F3op/F3t was the best one. For this best model, the top-down connection from L. F3op/F3t to L. SMG was significantly positive. By using diffusion-tensor imaging, we confirmed that the left dorsal pathway of the superior longitudinal and arcuate fasciculi consistently connected these regions. Lastly, we established that nonlinguistic order-related and error-related factors significantly activated the right (R.) lateral premotor cortex and R. F3op/F3t, respectively

  17. Study on the Key Factor Parameters to Increase Productivity in Construction and Manufacturing Industries.

    NASA Astrophysics Data System (ADS)

    Almazyed, K.; Alaswad, A.; Olabi, A. G.

    2016-02-01

    Proper management of human and non-human resources in construction and manufacturing projects can give-in considerable savings in time and cost. Construction and Manufacturing industry faces issues in connection with problems related with productivity and the problems are usually connected with performance of employees. The performance of employees is affected by many factors. In this paper a survey was made on respondents who are employed various projects of Saudi Arabia. The researcher developed a theoretical framework from the existing research which was used as a Model to collect and analyze the field data to test the hypothesis. In this research activity three predictors (commitment, job satisfaction and job performance) for determining the change in productivity. The results highlight that commitment and job performance (respectively) are the two predictors which are explaining 37% of variation in the productivity of the companies. The results also show that Job Satisfaction has no role in the prediction of productivity.

  18. Olive (Olea europaea L.) tree nitrogen status is a key factor for olive oil quality.

    PubMed

    Erel, Ran; Kerem, Zohar; Ben-Gal, Alon; Dag, Arnon; Schwartz, Amnon; Zipori, Isaac; Basheer, Loai; Yermiyahu, Uri

    2013-11-27

    The influence of macronutrient status on olive oil properties was studied for three years. Data were analyzed by a multivariate model considering N, P, K, and fruiting year as explanatory factors. Oil quality parameters were primarily associated with N concentration in leaves and fruits which increased with N in irrigation solution. The effect of P on oil quality was mainly indirect since increased P availability increased N accumulation. The potassium level had negligible effects. The oil phenolic content decreased linearly as a function of increased leaf N, indicating protein-phenol competition in leaves. The overall saturation level of the fatty acids decreased with fruit N, resulting in increased polyunsaturated fatty acids. Free fatty acids increased with increased levels of fruit N. High fruit load tended to reduce fruit N and subsequently improve oil quality. The effect of N on oil properties depended solely on its concentration in leaves or fruits, regardless of the cause.

  19. Merkel Cell Carcinoma: An Update of Key Imaging Techniques, Prognostic Factors, Treatment, and Follow-up.

    PubMed

    Llombart, B; Kindem, S; Chust, M

    2017-03-01

    Merkel cell carcinoma, though rare, is one of the most aggressive tumors a dermatologist faces. More than a third of patients with this diagnosis die from the disease. Numerous researchers have attempted to identify clinical and pathologic predictors to guide prognosis, but their studies have produced inconsistent results. Because the incidence of Merkel cell carcinoma is low and it appears in patients of advanced age, prospective studies have not been done and no clear treatment algorithm has been developed. This review aims to provide an exhaustive, up-to-date account of Merkel cell carcinoma for the dermatologist. We describe prognostic factors and the imaging techniques that are most appropriate for evaluating disease spread. We also discuss current debates on treating Merkel cell carcinoma.

  20. Hydrophobic environment is a key factor for the stability of thermophilic proteins.

    PubMed

    Gromiha, M Michael; Pathak, Manish C; Saraboji, Kadhirvel; Ortlund, Eric A; Gaucher, Eric A

    2013-04-01

    The stability of thermophilic proteins has been viewed from different perspectives and there is yet no unified principle to understand this stability. It would be valuable to reveal the most important interactions for designing thermostable proteins for such applications as industrial protein engineering. In this work, we have systematically analyzed the importance of various interactions by computing different parameters such as surrounding hydrophobicity, inter-residue interactions, ion-pairs and hydrogen bonds. The importance of each interaction has been determined by its predicted relative contribution in thermophiles versus the same contribution in mesophilic homologues based on a dataset of 373 protein families. We predict that hydrophobic environment is the major factor for the stability of thermophilic proteins and found that 80% of thermophilic proteins analyzed showed higher hydrophobicity than their mesophilic counterparts. Ion pairs, hydrogen bonds, and interaction energy are also important and favored in 68%, 50%, and 62% of thermophilic proteins, respectively. Interestingly, thermophilic proteins with decreased hydrophobic environments display a greater number of hydrogen bonds and/or ion pairs. The systematic elimination of mesophilic proteins based on surrounding hydrophobicity, interaction energy, and ion pairs/hydrogen bonds, led to correctly identifying 95% of the thermophilic proteins in our analyses. Our analysis was also applied to another, more refined set of 102 thermophilic-mesophilic pairs, which again identified hydrophobicity as a dominant property in 71% of the thermophilic proteins. Further, the notion of surrounding hydrophobicity, which characterizes the hydrophobic behavior of residues in a protein environment, has been applied to the three-dimensional structures of elongation factor-Tu proteins and we found that the thermophilic proteins are enriched with a hydrophobic environment. The results obtained in this work highlight the

  1. Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

    PubMed

    Sato, Takeo; Maekawa, Shugo; Konishi, Mineko; Yoshioka, Nozomi; Sasaki, Yuki; Maeda, Haruna; Ishida, Tetsuya; Kato, Yuki; Yamaguchi, Junji; Yanagisawa, Shuichi

    2017-01-29

    Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis.

  2. Security analysis and improvements of two-factor mutual authentication with key agreement in wireless sensor networks.

    PubMed

    Kim, Jiye; Lee, Donghoon; Jeon, Woongryul; Lee, Youngsook; Won, Dongho

    2014-04-09

    User authentication and key management are two important security issues in WSNs (Wireless Sensor Networks). In WSNs, for some applications, the user needs to obtain real-time data directly from sensors and several user authentication schemes have been recently proposed for this case. We found that a two-factor mutual authentication scheme with key agreement in WSNs is vulnerable to gateway node bypassing attacks and user impersonation attacks using secret data stored in sensor nodes or an attacker's own smart card. In this paper, we propose an improved scheme to overcome these security weaknesses by storing secret data in unique ciphertext form in each node. In addition, our proposed scheme should provide not only security, but also efficiency since sensors in a WSN operate with resource constraints such as limited power, computation, and storage space. Therefore, we also analyze the performance of the proposed scheme by comparing its computation and communication costs with those of other schemes.

  3. Anabolic and androgenic activities of 19-nor-testosterone steroids: QSAR study using quantum and physicochemical molecular descriptors.

    PubMed

    Alvarez-Ginarte, Yoanna María; Montero-Cabrera, Luis Alberto; de la Vega, José Manuel García; Noheda-Marín, Pedro; Marrero-Ponce, Yovani; Ruíz-García, José Alberto

    2011-08-01

    Quantitative structure-activity relationship (QSAR) study of 19-nor-testosterone steroids family was performed using quantum and physicochemical molecular descriptors. The quantum-chemical descriptors were calculated using semiempirical calculations. The descriptor values were statistically correlated using multi-linear regression analysis. The QSAR study indicated that the electronic properties of these derivatives have significant relationship with observed biological activities. The found QSAR equations explain that the energy difference between the LUMO and HOMO, the total dipole moment, the chemical potential and the value of the net charge of different carbon atoms in the steroid nucleus showed key interaction of these steroids with their anabolic-androgenic receptor binding site. The calculated values predict that the 17α-cyclopropyl-17β, 3β-hydroxy-4-estrene compound presents the highest anabolic-androgenic ratio (AAR) and the 7α-methyl-17β-acetoxy-estr-4-en-3-one compound the lowest AAR. This study might be helpful in the future successful identification of "real" or "virtual" anabolic-androgenic steroids.

  4. MicroRNA and Transcription Factor Gene Regulatory Network Analysis Reveals Key Regulatory Elements Associated with Prostate Cancer Progression

    PubMed Central

    Sadeghi, Mehdi; Ranjbar, Bijan; Ganjalikhany, Mohamad Reza; M. Khan, Faiz; Schmitz, Ulf; Wolkenhauer, Olaf; Gupta, Shailendra K.

    2016-01-01

    Technological and methodological advances in multi-omics data generation and integration approaches help elucidate genetic features of complex biological traits and diseases such as prostate cancer. Due to its heterogeneity, the identification of key functional components involved in the regulation and progression of prostate cancer is a methodological challenge. In this study, we identified key regulatory interactions responsible for primary to metastasis transitions in prostate cancer using network inference approaches by integrating patient derived transcriptomic and miRomics data into gene/miRNA/transcription factor regulatory networks. One such network was derived for each of the clinical states of prostate cancer based on differentially expressed and significantly correlated gene, miRNA and TF pairs from the patient data. We identified key elements of each network using a network analysis approach and validated our results using patient survival analysis. We observed that HOXD10, BCL2 and PGR are the most important factors affected in primary prostate samples, whereas, in the metastatic state, STAT3, JUN and JUNB are playing a central role. Benefiting integrative networks our analysis suggests that some of these molecules were targeted by several overexpressed miRNAs which may have a major effect on the dysregulation of these molecules. For example, in the metastatic tumors five miRNAs (miR-671-5p, miR-665, miR-663, miR-512-3p and miR-371-5p) are mainly responsible for the dysregulation of STAT3 and hence can provide an opportunity for early detection of metastasis and development of alternative therapeutic approaches. Our findings deliver new details on key functional components in prostate cancer progression and provide opportunities for the development of alternative therapeutic approaches. PMID:28005952

  5. Key factors controlling microbial community response after a fire: importance of severity and recurrence

    NASA Astrophysics Data System (ADS)

    Lombao, Alba; Barreiro, Ana; Martín, Ángela; Díaz-Raviña, Montserrat

    2015-04-01

    Microorganisms play an important role in forest ecosystems, especially after fire when vegetation is destroyed and soil is bared. Fire severity and recurrence might be one of main factors controlling the microbial response after a wildfire but information about this topic is scarce. The aim of this study is to evaluate the influence of fire regimen (recurrence and severity) on soil microbial community structure by means of the analysis of phospholipid fatty acid (PLFA). The study was performed with unburned and burned samples collected from the top layer of a soil affected by a high severity fire (Laza, NW Spain) heated under laboratory conditions at different temperatures (50°C, 75°C, 100°C, 125°C, 150°C, 175°C, 200°C, 300°C) to simulate different fire intensities; the process was repeated after further soil recovery (1 month incubation) to simulate fire recurrence. The soil temperature was measured with thermocouples and used to calculate the degree-hours as estimation of the amount of heat supplied to the samples (fire severity). The PLFA analysis was used to estimate total biomass and the biomass of specific groups (bacteria, fungi, gram-positive bacteria and gram-negative bacteria) as well as microbial community structure (PLFA pattern) and PLFA data were analyzed by means of principal component analysis (PCA) in order to identify main factors determining microbial community structure. The results of PCA, performed with the whole PLFA data set, showed that first component explained 35% of variation and clearly allow us to differentiate unburned samples from the corresponding burned samples, while the second component, explaining 16% of variation, separated samples according the heating temperature. A marked impact of fire regimen on soil microorganisms was detected; the microbial community response varied depending on previous history of soil heating and the magnitude of changes in the PLFA pattern was related to the amount of heat supplied to the

  6. Membrane domain formation—a key factor for targeted intracellular drug delivery

    PubMed Central

    Popov-Čeleketić, Dušan; van Bergen en Henegouwen, Paul M. P.

    2014-01-01

    Protein molecules, toxins and viruses internalize into the cell via receptor-mediated endocytosis (RME) using specific proteins and lipids in the plasma membrane. The plasma membrane is a barrier for many pharmaceutical agents to enter into the cytoplasm of target cells. In the case of cancer cells, tissue-specific biomarkers in the plasma membrane, like cancer-specific growth factor receptors, could be excellent candidates for RME-dependent drug delivery. Recent data suggest that agent binding to these receptors at the cell surface, resulting in membrane domain formation by receptor clustering, can be used for the initiation of RME. As a result, these pharmaceutical agents are internalized into the cells and follow different routes until they reach their final intracellular targets like lysosomes or Golgi. We propose that clustering induced formation of plasma membrane microdomains enriched in receptors, sphingolipids, and inositol lipids, leads to membrane bending which functions as the onset of RME. In this review we will focus on the role of domain formation in RME and discuss potential applications for targeted intracellular drug delivery. PMID:25520666

  7. Corticotropin releasing factor: a key role in the neurobiology of addiction.

    PubMed

    Zorrilla, Eric P; Logrip, Marian L; Koob, George F

    2014-04-01

    Drug addiction is a chronically relapsing disorder characterized by loss of control over intake and dysregulation of stress-related brain emotional systems. Since the discovery by Wylie Vale and his colleagues of corticotropin-releasing factor (CRF) and the structurally-related urocortins, CRF systems have emerged as mediators of the body's response to stress. Relatedly, CRF systems have a prominent role in driving addiction via actions in the central extended amygdala, producing anxiety-like behavior, reward deficits, excessive, compulsive-like drug self-administration and stress-induced reinstatement of drug seeking. CRF neuron activation in the medial prefrontal cortex may also contribute to the loss of control. Polymorphisms in CRF system molecules are associated with drug use phenotypes in humans, often in interaction with stress history. Drug discovery efforts have yielded brain-penetrant CRF1 antagonists with activity in preclinical models of addiction. The results support the hypothesis that brain CRF-CRF1 systems contribute to the etiology and maintenance of addiction.

  8. A Robust and Anonymous Two Factor Authentication and Key Agreement Protocol for Telecare Medicine Information Systems.

    PubMed

    Xiong, Hu; Tao, Junyi; Chen, Yanan

    2016-11-01

    Nowadays people can get many services including health-care services from distributed information systems remotely via public network. By considering that these systems are built on public network, they are vulnerable to many malicious attacks. Hence it is necessary to introduce an effective mechanism to protect both users and severs. Recently many two-factor authentication schemes have been proposed to achieve this goal. In 2016, Li et al. demonstrated that Lee et al.'s scheme was not satisfactory to be deployed in practice because of its security weaknesses and then proposed a security enhanced scheme to overcome these drawbacks. In this paper, we analyze Li et al.'s scheme is still not satisfactory to be applied in telecare medicine information systems (TMIS) because it fails to withstand off-line dictionary attack and known session-specific temporary information attack. Moreover, their scheme cannot provide card revocation services for lost smart card. In order to solve these security problems, we propose an improved scheme. Then we analyze our scheme by using BAN-logic model and compare the improved scheme with related schemes to prove that our scheme is advantageous to be applied in practice.

  9. Physiologically-based toxicokinetic models help identifying the key factors affecting contaminant uptake during flood events.

    PubMed

    Brinkmann, Markus; Eichbaum, Kathrin; Kammann, Ulrike; Hudjetz, Sebastian; Cofalla, Catrina; Buchinger, Sebastian; Reifferscheid, Georg; Schüttrumpf, Holger; Preuss, Thomas; Hollert, Henner

    2014-07-01

    As a consequence of global climate change, we will be likely facing an increasing frequency and intensity of flood events. Thus, the ecotoxicological relevance of sediment re-suspension is of growing concern. It is vital to understand contaminant uptake from suspended sediments and relate it to effects in aquatic biota. Here we report on a computational study that utilizes a physiologically based toxicokinetic model to predict uptake, metabolism and excretion of sediment-borne pyrene in rainbow trout (Oncorhynchus mykiss). To this end, data from two experimental studies were compared with the model predictions: (a) batch re-suspension experiments with constant concentration of suspended particulate matter at two different temperatures (12 and 24°C), and (b) simulated flood events in an annular flume. The model predicted both the final concentrations and the kinetics of 1-hydroxypyrene secretion into the gall bladder of exposed rainbow trout well. We were able to show that exhaustive exercise during exposure in simulated flood events can lead to increased levels of biliary metabolites and identified cardiac output and effective respiratory volume as the two most important factors for contaminant uptake. The results of our study clearly demonstrate the relevance and the necessity to investigate uptake of contaminants from suspended sediments under realistic exposure scenarios.

  10. Economic incentives to promote healthier food purchases: exploring acceptability and key factors for success.

    PubMed

    Ni Mhurchu, Cliona; Eyles, Helen; Dixon, Robyn; Matoe, Leonie; Teevale, Tasileta; Meagher-Lundberg, Patricia

    2012-09-01

    Despite increasing interest, little is known about the beliefs and views of the public in relation to the use of economic incentives as a means to promote healthy eating. This study explores views of ethnically and socioeconomically diverse shoppers regarding acceptability of economic incentives to promote healthier food purchases, and factors likely to affect the success of such schemes. Six focus groups (n = 36 participants; 14 Māori, 12 Pacific, 10 non-ethnic specific low income), were held in Auckland, New Zealand, in October 2009. A general inductive approach was used to identify common themes. The single most important reported food purchasing influence was cost. Focus group participants viewed the concept of economic incentives to promote healthy eating positively, as long as such schemes provided worthwhile incentives, and were simple and convenient to use. The preferred option for delivery was a pre-loaded electronic swipe card. Fruit and vegetables were the food group most participants said they would like to see incentivized. There was marked variability in the incentive amount thought sufficient to promote participation in such a scheme. Our findings suggest economic incentives hold promise as a means to promote healthier household food purchases, and their effectiveness should be evaluated using robust, randomized trials.

  11. Leptin in early life: a key factor for the development of the adult metabolic profile.

    PubMed

    Granado, Miriam; Fuente-Martín, Esther; García-Cáceres, Cristina; Argente, Jesús; Chowen, Julie A

    2012-01-01

    Leptin levels during the perinatal period are important for the development of metabolic systems involved in energy homeostasis. In rodents, there is a postnatal leptin surge, with circulating leptin levels increasing around postnatal day (PND) 5 and peaking between PND 9 and PND 10. At this time circulating leptin acts as an important trophic factor for the development of hypothalamic circuits that control energy homeostasis and food seeking and reward behaviors. Blunting the postnatal leptin surge results in long-term leptin insensitivity and increased susceptibility to diet-induced obesity during adulthood. Pharmacologically increased leptin levels in the postnatal period also have long-term effects on metabolism. Nevertheless, this effect is controversial as postnatal hyperleptinemia is reported to both increase and decrease the predisposition to obesity in adulthood. The different effects reported in the literature could be explained by the different moments at which this hormone was administered, suggesting that modifications of the neonatal leptin surge at specific time points could selectively affect the development of central and peripheral systems that are undergoing modifications at this moment resulting in different metabolic and behavioral outcomes. In addition, maternal nutrition and the hormonal environment during pregnancy and lactation may also modulate the offspring's response to postnatal modifications in leptin levels. This review highlights the importance of leptin levels during the perinatal period in the development of metabolic systems that control energy homeostasis and how modifications of these levels may induce long-lasting and potentially irreversible effects on metabolism.

  12. Zinc regulates a key transcriptional pathway for epileptogenesis via metal-regulatory transcription factor 1

    PubMed Central

    van Loo, Karen M. J.; Schaub, Christina; Pitsch, Julika; Kulbida, Rebecca; Opitz, Thoralf; Ekstein, Dana; Dalal, Adam; Urbach, Horst; Beck, Heinz; Yaari, Yoel; Schoch, Susanne; Becker, Albert J.

    2015-01-01

    Temporal lobe epilepsy (TLE) is the most common focal seizure disorder in adults. In many patients, transient brain insults, including status epilepticus (SE), are followed by a latent period of epileptogenesis, preceding the emergence of clinical seizures. In experimental animals, transcriptional upregulation of CaV3.2 T-type Ca2+-channels, resulting in an increased propensity for burst discharges of hippocampal neurons, is an important trigger for epileptogenesis. Here we provide evidence that the metal-regulatory transcription factor 1 (MTF1) mediates the increase of CaV3.2 mRNA and intrinsic excitability consequent to a rise in intracellular Zn2+ that is associated with SE. Adeno-associated viral (rAAV) transfer of MTF1 into murine hippocampi leads to increased CaV3.2 mRNA. Conversely, rAAV-mediated expression of a dominant-negative MTF1 abolishes SE-induced CaV3.2 mRNA upregulation and attenuates epileptogenesis. Finally, data from resected human hippocampi surgically treated for pharmacoresistant TLE support the Zn2+-MTF1-CaV3.2 cascade, thus providing new vistas for preventing and treating TLE. PMID:26498180

  13. Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells

    PubMed Central

    Noto, A; Raffa, S; De Vitis, C; Roscilli, G; Malpicci, D; Coluccia, P; Di Napoli, A; Ricci, A; Giovagnoli, M R; Aurisicchio, L; Torrisi, M R; Ciliberto, G; Mancini, R

    2013-01-01

    In recent years, studies of cancer development and recurrence have been influenced by the cancer stem cells (CSCs)/cancer-initiating cells (CICs) hypothesis. According to this, cancer is sustained by highly positioned, chemoresistant cells with extensive capacity of self renewal, which are responsible for disease relapse after chemotherapy. Growth of cancer cells as three-dimensional non-adherent spheroids is regarded as a useful methodology to enrich for cells endowed with CSC-like features. We have recently reported that cell cultures derived from malignant pleural effusions (MPEs) of patients affected by adenocarcinoma of the lung are able to efficiently form spheroids in non-adherent conditions supplemented with growth factors. By expression profiling, we were able to identify a set of genes whose expression is significantly upregulated in lung tumor spheroids versus adherent cultures. One of the most strongly upregulated gene was stearoyl-CoA desaturase (SCD1), the main enzyme responsible for the conversion of saturated into monounsaturated fatty acids. In the present study, we show both by RNA interference and through the use of a small molecule inhibitor that SCD1 is required for lung cancer spheroids propagation both in stable cell lines and in MPE-derived primary tumor cultures. Morphological examination and image analysis of the tumor spheroids formed in the presence of SCD1 inhibitors showed a different pattern of growth characterized by irregular cell aggregates. Electron microscopy revealed that the treated spheroids displayed several features of cellular damage and immunofluorescence analysis on optical serial sections showed apoptotic cells positive for the M30 marker, most of them positive also for the stemness marker ALDH1A1, thus suggesting that the SCD1 inhibitor is selectively killing cells with stem-like properties. Furthermore, SCD1-inhibited lung cancer cells were strongly impaired in their in vivo tumorigenicity and ALDH1A1 expression. These

  14. Key geochemical factors regulating Mn(IV)-catalyzed anaerobic nitrification in coastal marine sediments

    NASA Astrophysics Data System (ADS)

    Lin, Hui; Taillefert, Martial

    2014-05-01

    The reduction of Mn(IV) oxides coupled to the anaerobic oxidation of NH4+ has been proposed for more than a decade to contribute to the fixed nitrogen pool in marine sediments, yet the existence of this process is still under debate. In this study, surface sediments from an intertidal salt marsh were incubated with MnO2 in the presence of elevated concentrations of NH4+ to test the hypothesis that the reduction of Mn(IV) oxides catalyzes anaerobic NH4+ oxidation to NO2- or NO3-. Geochemical factors such as the ratio of Mn(IV) to NH4+, the type of Mn(IV) oxides (amorphous or colloidal MnO2), and the redox potential of the sediment significantly affect the activity of anaerobic nitrification. Incubations show that the net production of NO3- is stimulated under anaerobic conditions with external addition of colloidal but not amorphous MnO2 and is facilitated by the presence of high concentrations of NH4+. Mass balance calculations demonstrate that anaerobic NH4+ oxidation contributes to the net consumption of NH4+, providing another piece of evidence for the occurrence of Mn(IV)-catalyzed anaerobic nitrification in coastal marine sediments. Finally, anaerobic nitrification is stimulated by the amendment of small concentrations of NO3- or the absence of sulfate reduction, suggesting that moderately reducing conditions favor anaerobic NH4+ oxidation. Overall, these findings suggest that Mn(IV)-catalyzed anaerobic nitrification in suboxic sediments with high N/Mn concentration ratios and highly reactive manganese oxides may be an important source of NO2- and NO3- for subsequent marine nitrogen loss via denitrification or anammox.

  15. DNA lesions, inducible DNA repair, and cell division: Three key factors in mutagenesis and carcinogenesis

    SciTech Connect

    Ames, B.N.; Shigenaga, M.K.; Gold, L.S.

    1993-12-01

    DNA lesions that escape repair have a certain probability of giving rise to mutations when the cell divides. Endogenous DNA damage is high: 10{sup 6} oxidative lesions are present per rat cell. An exogenous mutagen produces an increment in lesions over the background rate of endogenous lesions. The effectiveness of a particular lesion depends on whether it is excised by a DNA repair system and the probability that it gives rise to a mutation when the cell divides. When the cell divides, an unrepaired DNA lesion has a certain probability of giving rise to a mutation. Thus, an important factor in the mutagenic effect of an exogenous agent whether it is genotoxic or non-genotoxic, is the increment it causes over the background cell division rate (mitogenesis) in cells that appear to matter most in cancer, the stem cells, which are not on their way to being discarded. Increasing their cell division rate increases by high doses of chemicals. If both the rate of DNA lesions and cell division are increased, then there will be a multiplicative effect on mutagenesis (and carcinogenesis), for example, by high doses of a mutagen that also increases mitogenesis through cell killing. The defense system against reactive electrophilic mutagens, such as the glutathione transferases, are also almost all inducible and buffer cells against increments in active forms of chemicals that can cause DNA lesions. A variety of DNA repair defense systems, almost all inducible, buffer the cell against any increment in DNA lesions. Therefore, the effect of a particular chemical insult depends on the level of each defense, which in turn depends on the past history of exposure. Exogenous agents can influence the induction and effectiveness of these defenses. Defenses can be partially disabled by lack of particular micronutrients in the diet (e.g., antioxidants).

  16. Key Role of Amino Acid Repeat Expansions in the Functional Diversification of Duplicated Transcription Factors

    PubMed Central

    Radó-Trilla, Núria; Arató, Krisztina; Pegueroles, Cinta; Raya, Alicia; de la Luna, Susana; Albà, M. Mar

    2015-01-01

    The high regulatory complexity of vertebrates has been related to two rounds of whole genome duplication (2R-WGD) that occurred before the divergence of the major vertebrate groups. Following these events, many developmental transcription factors (TFs) were retained in multiple copies and subsequently specialized in diverse functions, whereas others reverted to their singleton state. TFs are known to be generally rich in amino acid repeats or low-complexity regions (LCRs), such as polyalanine or polyglutamine runs, which can evolve rapidly and potentially influence the transcriptional activity of the protein. Here we test the hypothesis that LCRs have played a major role in the diversification of TF gene duplicates. We find that nearly half of the TF gene families originated during the 2R-WGD contains LCRs. The number of gene duplicates with LCRs is 155 out of 550 analyzed (28%), about twice as many as the number of single copy genes with LCRs (15 out of 115, 13%). In addition, duplicated TFs preferentially accumulate certain LCR types, the most prominent of which are alanine repeats. We experimentally test the role of alanine-rich LCRs in two different TF gene families, PHOX2A/PHOX2B and LHX2/LHX9. In both cases, the presence of the alanine-rich LCR in one of the copies (PHOX2B and LHX2) significantly increases the capacity of the TF to activate transcription. Taken together, the results provide strong evidence that LCRs are important driving forces of evolutionary change in duplicated genes. PMID:25931513

  17. Influence of anabolic combinations of an androgen plus an estrogen on biochemical pathways in bovine uterine endometrium and ovary.

    PubMed

    Becker, C; Riedmaier, I; Reiter, M; Tichopad, A; Groot, M J; Stolker, A A M; Pfaffl, M W; Nielen, M F W; Meyer, H H D

    2011-07-01

    The application of anabolic steroids in food producing animals is forbidden in the EU since 1988, but the abuse of such drugs is a potential problem. The existing test systems are based on known compounds and can be eluded by newly emerging substances. The examination of physiological effects of anabolic hormones on different tissues to indirectly detect misuse might overcome this problem. Two studies were conducted with post-pubertal 24-months old Nguni heifers and pre-pubertal female 2-4 weeks old Holstein Friesian calves, respectively. The animals of the accordant treatment groups were administered combinations of estrogenic and androgenic compounds. The measurement of the gene expression pattern was undertaken with RT-qPCR. Target genes of different functional groups (receptors, angiogenesis, steroid synthesis, proliferation, apoptosis, nutrient metabolism and others) have been quantified. Several biochemical pathways were shown to be influenced by anabolic treatment. Both studies identified significant regulations in steroid and growth factor receptors (AR, ERβ, LHR, FSHR, Flt-1, PR, IGF-1R, Alk-6), angiogenic and tissue remodeling factors (VEGFs, FGFs, BMPs, ANGPT-2, MMPs, TIMP-2, CTSB), steroid synthesis (S5A1, HSD17, CYP19A1), proliferation (TNFα, IGF-1, IGFBPs, p53, c-fos; CEBPD, c-kit), apoptosis (CASP3, FasL, p53) and others (C7, INHA, STAR). Several genes were regulated to opposite directions in post-pubertal compared to pre-pubertal animals. PCA for Nguni heifers demonstrated a distinct separation between the control and the treatment group. In conclusion, anabolics modify hormone sensitivity and steroid synthesis, and they induce proliferative effects in the whole reproductive tract (uterus and ovary) as well as anti-angiogenic effects in the ovary. However, the extent will depend on the developmental stage of the animals.

  18. Transition of basaltic lava from pahoehoe to aa, Kilauea Volcano, Hawaii: Field observations and key factors

    USGS Publications Warehouse

    Peterson, D.W.; Tilling, R.I.

    1980-01-01

    Nearly all Hawaiian basaltic lava erupts as pahoehoe, and some changes to aa during flowage and cooling; factors governing the transition involve certain critical relations between viscosity and rate of shear strain. If the lava slows, cools, and stops in direct response to concomitant increase in viscosity before these critical relations are reached, it remains pahoehoe. But, if flow mechanics (flow rate, flow dimensions, slope, momentum, etc.) impel the lava to continue to move and deform even after it has become highly viscous, the critical relations may be reached and the lava changes to aa. Typical modes of transition from pahoehoe to aa include: (1) spontaneous formation of relatively stiff clots in parts of the flowing lava where shear rate is highest; these clots grow into discrete, rough, sticky masses to which the remaining fluid lava incrementally adheres; (2) fragmentation and immersion of solid or semi-solid surface crusts of pahoehoe by roiling movements of the flow, forming cores of discrete, tacky masses; (3) sudden renewed movement of lava stored and cooled within surface reservoirs to form clots. The masses, fragments, and clots in these transition modes are characterized by spinose, granulated surfaces; as flow movement continues, the masses and fragments aggregate, fracture, and grind together, completing the transition to aa. Observations show that the critical relation between viscosity and rate of shear strain is inverse: if viscosity is low, a high rate of shear is required to begin the transition to aa; conversely, if viscosity is high, a much lower rate of shear will induce the transition. These relations can be demonstrated qualitatively with simple graphs, which can be used to examine the flow history of any selected finite lava element by tracing the path represented by its changing viscosity and shear rate. A broad, diffuse "transition threshold zone" in these graphs portrays the inverse critical relation between viscosity and shear

  19. A key role of nuclear factor Y in the refeeding response of fatty acid synthase in adipocytes.

    PubMed

    Nishi-Tatsumi, Makiko; Yahagi, Naoya; Takeuchi, Yoshinori; Toya, Naoki; Takarada, Ayako; Murayama, Yuki; Aita, Yuichi; Sawada, Yoshikazu; Piao, Xiaoying; Oya, Yukari; Shikama, Akito; Masuda, Yukari; Kubota, Midori; Izumida, Yoshihiko; Matsuzaka, Takashi; Nakagawa, Yoshimi; Sekiya, Motohiro; Iizuka, Yoko; Kawakami, Yasushi; Kadowaki, Takashi; Yamada, Nobuhiro; Shimano, Hitoshi

    2017-03-09

    Fatty acid synthase (Fasn) is a key component of energy metabolism that is dynamically induced by food intake. Although extensive studies have revealed a number of transcription factors involved in the fasting/refeeding transition of Fasn expression in hepatocytes, much less evidence is available for adipocytes. Using the in vivo Ad-luc analytical system, we identified the inverted CCAAT element (ICE) around -100 nucleotides in the Fasn promoter as a critical cis-element for the refeeding response in adipocytes. Electrophoretic mobility shift assays and chromatin immunoprecipitation show that nuclear factor Y (NF-Y) binds to ICE specifically in refeeding states. Notably, the NF-Y binding to ICE is differently regulated between adipocytes and hepatocytes. These findings provide insights into the specific mechanisms controlling energy metabolism in adipocytes. This article is protected by copyright. All rights reserved.

  20. Privacy Protection for Telecare Medicine Information Systems Using a Chaotic Map-Based Three-Factor Authenticated Key Agreement Scheme.

    PubMed

    Zhang, Liping; Zhu, Shaohui; Tang, Shanyu

    2017-03-01

    Telecare medicine information systems (TMIS) provide flexible and convenient e-health care. However, the medical records transmitted in TMIS are exposed to unsecured public networks, so TMIS are more vulnerable to various types of security threats and attacks. To provide privacy protection for TMIS, a secure and efficient authenticated key agreement scheme is urgently needed to protect the sensitive medical data. Recently, Mishra et al. proposed a biometrics-based authenticated key agreement scheme for TMIS by using hash function and nonce, they claimed that their scheme could eliminate the security weaknesses of Yan et al.'s scheme and provide dynamic identity protection and user anonymity. In this paper, however, we demonstrate that Mishra et al.'s scheme suffers from replay attacks, man-in-the-middle attacks and fails to provide perfect forward secrecy. To overcome the weaknesses of Mishra et al.'s scheme, we then propose a three-factor authenticated key agreement scheme to enable the patient to enjoy the remote healthcare services via TMIS with privacy protection. The chaotic map-based cryptography is employed in the proposed scheme to achieve a delicate balance of security and performance. Security analysis demonstrates that the proposed scheme resists various attacks and provides several attractive security properties. Performance evaluation shows that the proposed scheme increases efficiency in comparison with other related schemes.

  1. SND1, a NAC domain transcription factor, is a key regulator of secondary wall synthesis in fibers of Arabidopsis.

    PubMed

    Zhong, Ruiqin; Demura, Taku; Ye, Zheng-Hua

    2006-11-01

    Secondary walls in fibers and tracheary elements constitute the most abundant biomass produced by plants. Although a number of genes involved in the biosynthesis of secondary wall components have been characterized, little is known about the molecular mechanisms underlying the coordinated expression of these genes. Here, we demonstrate that the Arabidopsis thaliana NAC (for NAM, ATAF1/2, and CUC2) domain transcription factor, SND1 (for secondary wall-associated NAC domain protein), is a key transcriptional switch regulating secondary wall synthesis in fibers. We show that SND1 is expressed specifically in interfascicular fibers and xylary fibers in stems and that dominant repression of SND1 causes a drastic reduction in the secondary wall thickening of fibers. Ectopic overexpression of SND1 results in activation of the expression of secondary wall biosynthetic genes, leading to massive deposition of secondary walls in cells that are normally nonsclerenchymatous. In addition, we have found that SND1 upregulates the expression of several transcription factors that are highly expressed in fibers during secondary wall synthesis. Together, our results reveal that SND1 is a key transcriptional activator involved in secondary wall biosynthesis in fibers.

  2. Integrated genome-wide chromatin occupancy and expression analyses identify key myeloid pro-differentiation transcription factors repressed by Myb.

    PubMed

    Zhao, Liang; Glazov, Evgeny A; Pattabiraman, Diwakar R; Al-Owaidi, Faisal; Zhang, Ping; Brown, Matthew A; Leo, Paul J; Gonda, Thomas J

    2011-06-01

    To gain insight into the mechanisms by which the Myb transcription factor controls normal hematopoiesis and particularly, how it contributes to leukemogenesis, we mapped the genome-wide occupancy of Myb by chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) in ERMYB myeloid progenitor cells. By integrating the genome occupancy data with whole genome expression profiling data, we identified a Myb-regulated transcriptional program. Gene signatures for leukemia stem cells, normal hematopoietic stem/progenitor cells and myeloid development were overrepresented in 2368 Myb regulated genes. Of these, Myb bound directly near or within 793 genes. Myb directly activates some genes known critical in maintaining hematopoietic stem cells, such as Gfi1 and Cited2. Importantly, we also show that, despite being usually considered as a transactivator, Myb also functions to repress approximately half of its direct targets, including several key regulators of myeloid differentiation, such as Sfpi1 (also known as Pu.1), Runx1, Junb and Cebpb. Furthermore, our results demonstrate that interaction with p300, an established coactivator for Myb, is unexpectedly required for Myb-mediated transcriptional repression. We propose that the repression of the above mentioned key pro-differentiation factors may contribute essentially to Myb's ability to suppress differentiation and promote self-renewal, thus maintaining progenitor cells in an undifferentiated state and promoting leukemic transformation.

  3. The Metabolomic Signature of Malignant Glioma Reflects Accelerated Anabolic Metabolism

    PubMed Central

    Chinnaiyan, Prakash; Kensicki, Elizabeth; Bloom, Gregory; Prabhu, Antony; Sarcar, Bhaswati; Kahali, Soumen; Eschrich, Steven; Qu, Xiaotao; Forsyth, Peter; Gillies, Robert

    2015-01-01

    Although considerable progress has been made toward understanding glioblastoma biology through large-scale genetic and protein expression analyses, little is known about the underlying metabolic alterations promoting their aggressive phenotype. We conducted global metabolomic profiling on patient-derived glioma specimens and identified specific metabolic programs differentiating low- and high-grade tumors, with the metabolic signature of glioblastoma reflecting accelerated anabolic metabolism. When coupled with transcriptional profiles, we identified the metabolic phenotype of the mesenchymal subtype to consist of accumulation of the glycolytic intermediate phosphoenolpyruvate and decreased pyruvate kinase activity. Unbiased hierarchical clustering of metabolomic profiles identified three subclasses, which we term energetic, anabolic, and phospholipid catabolism with prognostic relevance. These studies represent the first global metabolomic profiling of glioma, offering a previously undescribed window into their metabolic heterogeneity, and provide the requisite framework for strategies designed to target metabolism in this rapidly fatal malignancy. PMID:23026133

  4. Stevens-Johnson syndrome and abuse of anabolic steroids

    PubMed Central

    2017-01-01

    Stevens-Johnson syndrome (SJS) is characterized by mucocutaneous tenderness and typical hemorrhagic erosions, erythema and epidermal detachment presenting as blisters and areas of denuded skin. SJS is often observed after drug use as well as after bacterial or viral infections. Several drugs are at high risk of inducing SJS, but there are no cases in the English literature regarding anabolic steroid use triggering SJS. In our paper, we describe a case in which use of anabolic androgenic steroids (AAS) was associated with SJS. The patient participated in competitive body-building and regularly took variable doses of AAS. Initial symptoms (headache, weakness, pharyngodynia, and fever) were ignored. After a week he presented to the Emergency Department with a burning sensation on the mouth, lips, and eyes. Painful, erythematous, maculopapular, and vesicular lesions appeared all over the body, including on the genitals. During hospitalization, he also developed a cardiac complication. The patient had not taken any drugs except AAS. PMID:28280713

  5. ANABOLIC-ANDROGENIC STEROID DEPENDENCE? INSIGHTS FROM ANIMALS AND HUMANS

    PubMed Central

    Wood, Ruth I.

    2008-01-01

    Anabolic-androgenic steroids (AAS) are drugs of abuse. They are taken in large quantities by athletes and others to increase performance, with negative health consequences. As a result, in 1991 testosterone and related AAS were declared controlled substances. However, the relative abuse and dependence liability of AAS have not been fully characterized. In humans, it is difficult to separate the direct psychoactive effects of AAS from reinforcement due to their systemic anabolic effects. However, using conditioned place preference and self-administration, studies in animals have demonstrated that AAS are reinforcing in a context where athletic performance is irrelevant. Furthermore, AAS share brain sites of action and neurotransmitter systems in common with other drugs of abuse. In particular, recent evidence links AAS with opioids. In humans, AAS abuse is associated with prescription opioid use. In animals, AAS overdose produces symptoms resembling opioid overdose, and AAS modify the activity of the endogenous opioid system. PMID:18275992

  6. Anabolic steroid abuse causing recurrent hepatic adenomas and hemorrhage.

    PubMed

    Martin, Nicole M; Abu Dayyeh, Barham K; Chung, Raymond T

    2008-07-28

    Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re-growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.

  7. Adverse effects of anabolic steroids in athletes. A constant threat.

    PubMed

    Maravelias, C; Dona, A; Stefanidou, M; Spiliopoulou, C

    2005-09-15

    Anabolic-androgenic steroids (AAS) are used as ergogenic aids by athletes and non-athletes to enhance performance by augmenting muscular development and strength. AAS administration is often associated with various adverse effects that are generally dose related. High and multi-doses of AAS used for athletic enhancement can lead to serious and irreversible organ damage. Among the most common adverse effects of AAS are some degree of reduced fertility and gynecomastia in males and masculinization in women and children. Other adverse effects include hypertension and atherosclerosis, blood clotting, jaundice, hepatic neoplasms and carcinoma, tendon damage, psychiatric and behavioral disorders. More specifically, this article reviews the reproductive, hepatic, cardiovascular, hematological, cerebrovascular, musculoskeletal, endocrine, renal, immunologic and psychologic effects. Drug-prevention counseling to athletes is highlighted and the use of anabolic steroids is must be avoided, emphasizing that sports goals may be met within the framework of honest competition, free of doping substances.

  8. Anabolic-androgenic steroid dependence? Insights from animals and humans.

    PubMed

    Wood, Ruth I

    2008-10-01

    Anabolic-androgenic steroids (AAS) are drugs of abuse. They are taken in large quantities by athletes and others to increase performance, with negative health consequences. As a result, in 1991 testosterone and related AAS were declared controlled substances. However, the relative abuse and dependence liability of AAS have not been fully characterized. In humans, it is difficult to separate the direct psychoactive effects of AAS from reinforcement due to their systemic anabolic effects. However, using conditioned place preference and self-administration, studies in animals have demonstrated that AAS are reinforcing in a context where athletic performance is irrelevant. Furthermore, AAS share brain sites of action and neurotransmitter systems in common with other drugs of abuse. In particular, recent evidence links AAS with opioids. In humans, AAS abuse is associated with prescription opioid use. In animals, AAS overdose produces symptoms resembling opioid overdose, and AAS modify the activity of the endogenous opioid system.

  9. Anabolic androgenic steroids in delayed diagnosis of tuberculosis

    PubMed Central

    Upadhyaya, Suneet K.; Sharma, Archana; Rai, Deependra K.; Thawani, Vijay

    2012-01-01

    This is the first case report depicting masking of symptoms of intestinal tuberculosis by anabolic androgenic steroids (AAS) causing delay in diagnosis which lead to a major surgery. Negative tuberculosis skin test (TST) probably due to immunomodulating effects of AAS also contributed to the delay. Patient also had early dependence on AAS and rapid growth of scrotal sebaceous cysts, findings of which have not yet been reported. PMID:23326112

  10. Comparative effectiveness of somatotropin and anabolic steroids in feedlot steers.

    PubMed

    Preston, R L; Bartle, S J; Kasser, T R; Day, J W; Veenhuizen, J J; Baile, C A

    1995-04-01

    Crossbred steers (n = 252, BW = 379 +/- 28 kg) were allotted to 42 pens in a 2 x 3 factorial arrangement of treatments: control or steroid implant (STR; estradiol benzoate+progesterone [three lighter blocks reimplanted on d 84] and trenbolone acetate [reimplanted on d 63]), and either 0, 80, or 160 mg/wk of recombinant bovine somatotropin (bST). Steers were adapted to the finishing diet (12% roughage equivalent, 13% CP) before the start of the experiment and fed for 84 or 119 d. Blood samples were taken on d 0, 14, 28, 56, and 84 for plasma urea N (PUN), serum somatotropin (ST), plasma insulin-like growth factor I (IGF-I), and plasma amino acid assay. Few interactions were noted (P > .1). Gain was increased by both treatments: 1.30 vs 1.66 kg/d for control vs. STR (P < .001) and 1.44, 1.49, and 1.51 kg/d (linear, P = .07) for 0, 80, and 160 mg of bST/wk, respectively. Gain efficiency was also improved: 169 vs 205 g/kg (P < .001) and 177, 189, and 195 g/kg (linear, P < .001), respectively. Average PUN was decreased (P < .001) 29% by STR and decreased 17 and 29% by 80 and 160 mg of bST/wk, respectively (linear, P < .001). Somatotropin decreased mean serum ST compared with controls; STR increased ST 36% compared with controls. Average plasma IGF-I was increased (P < .001) 12% by STR and 13 and 19% (linear, P < .001) by 80 and 160 mg of bST/wk, respectively. Both STR and bST influenced (P < .05) plasma amino acid profiles. Indicators of carcass fatness were decreased linearly (P < .05) by bST; STR implant tended to decrease carcass fatness and increase longissimus muscle area, which was related to carcass weight. The anabolic effects of STR and bST were found to be additive and possibly independent in feedlot steers.

  11. Doping with growth hormone/IGF-1, anabolic steroids or erythropoietin: is there a cancer risk?

    PubMed

    Tentori, Lucio; Graziani, Grazia

    2007-05-01

    Anabolic steroid and peptide hormones or growth factors are utilized to increase the performance of athletes of professional or amateur sports. Despite their well-documented adverse effects, the use of some of these agents has significantly grown and has been extended also to non-athletes with the aim to improve appearance or to counteract ageing. Pre-clinical studies and epidemiological observations in patients with an excess of hormone production or in patients chronically treated with hormones/growth factors for various pathologies have warned about the potential risk of cancer development and progression which may be also associated to the use of certain doping agents. Anabolic steroids have been described to provoke liver tumours; growth hormone or high levels of its mediator insulin-like growth factor-1 (IGF-1) have been associated with colon, breast, and prostate cancers. Actually, IGF-1 promotes cell cycle progression and inhibits apoptosis either by triggering other growth factors or by interacting with pathways which have an established role in carcinogenesis and cancer promotion. More recently, the finding that erythropoietin (Epo) may promote angiogenesis and inhibit apoptosis or modulate chemo- or radiosensitivity in cancer cells expressing the Epo receptor, raised the concern that the use of recombinant Epo to increase tissue oxygenation might favour tumour survival and aggressiveness. Cancer risk associated to doping might be higher than that of patients using hormones/growth factors as replacement therapy, since enormous doses are taken by the athletes often for a long period of time. Moreover, these substances are often used in combination with other licit or illicit drugs and this renders almost unpredictable all the possible adverse effects including cancer. Anyway, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer.

  12. Studying work practices: a key factor in understanding accidents on the level triggered by a balance disturbance.

    PubMed

    Derosier, C; Leclercq, S; Rabardel, P; Langa, P

    2008-12-01

    Accidents on the level (AOL) rank second amongst the most numerous and serious occupational accidents with days lost in France and are a major health and safety problem in every sector of activity. The case study described in this paper was conducted at a metallurgical company with 300 employees. The aims of this work were dual: 1) to extend the general knowledge required for preventing these accidents; 2) to propose prevention measures to this company. Existing data on company occupational accidents were gathered and analysed to identify a work situation that appeared likely to cause AOL. This work situation was analysed in detail. Several risk factors were identified within this work situation, by way of interviews with 12 operators. These risk factors concerned various dimensions of the work situation, particularly its physical dimension (e.g. templates structure) and organisational dimension (e.g. parts availability). Interviews were conducted, focusing on risk factors perceived by operators and involving allo-confrontations based on accounts of four AOL occurring in this situation. Allo-confrontations were interviews confronting operators with a risk occupational situation that was accidental for one of their colleagues, the latter being absent from the interview. Results highlighted the fact that the work practices implemented are key factors in understanding these accidents. This study underlines the role of work practices in AOL causality and prevention. It also provides explanations associated with various work situation dimensions involving adoption of more or less safe work practices. AOL are serious and frequent in occupational situations. Injury claims analysis and interviews in an industrial company emphasise the specific characteristics of an occupational situation and of prevention actions forming the basis of an intervention. The need for a better understanding of factors affecting work practice is highlighted in relation to research.

  13. An Adipoinductive Role of Inflammation in Adipose Tissue Engineering: Key Factors in the Early Development of Engineered Soft Tissues

    PubMed Central

    Lilja, Heidi E.; Morrison, Wayne A.; Han, Xiao-Lian; Palmer, Jason; Taylor, Caroline; Tee, Richard; Möller, Andreas; Thompson, Erik W.

    2013-01-01

    Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue. PMID:23231040

  14. An adipoinductive role of inflammation in adipose tissue engineering: key factors in the early development of engineered soft tissues.

    PubMed

    Lilja, Heidi E; Morrison, Wayne A; Han, Xiao-Lian; Palmer, Jason; Taylor, Caroline; Tee, Richard; Möller, Andreas; Thompson, Erik W; Abberton, Keren M

    2013-05-15

    Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.

  15. Glucose and Insulin Stimulate Lipogenesis in Porcine Adipocytes: Dissimilar and Identical Regulation Pathway for Key Transcription Factors

    PubMed Central

    Hua, Zhang Guo; Xiong, Lu Jian; Yan, Chen; Wei, Dai Hong; YingPai, ZhaXi; Qing, Zhao Yong; Lin, Qiao Zi; Fei, Feng Ruo; Ling, Wang Ya; Ren, Ma Zhong

    2016-01-01

    Lipogenesis is under the concerted action of ChREBP, SREBP-1c and other transcription factors in response to glucose and insulin. The isolated porcine preadipocytes were differentiated into mature adipocytes to investigate the roles and interrelation of these transcription factors in the context of glucose- and insulin-induced lipogenesis in pigs. In ChREBP-silenced adipocytes, glucose-induced lipogenesis decreased by ~70%, however insulin-induced lipogenesis was unaffected. Moreover, insulin had no effect on ChREBP expression of unperturbed adipocytes irrespective of glucose concentration, suggesting ChREBP mediate glucose-induced lipogenesis. Insulin stimulated SREBP-1c expression and when SREBP-1c activation was blocked, and the insulin-induced lipogenesis decreased by ~55%, suggesting SREBP-1c is a key transcription factor mediating insulin-induced lipogenesis. LXRα activation promoted lipogenesis and lipogenic genes expression. In ChREBP-silenced or SREBP-1c activation blocked adipocytes, LXRα activation facilitated lipogenesis and SREBP-1c expression, but had no effect on ChREBP expression. Therefore, LXRα might mediate lipogenesis via SREBP-1c rather than ChREBP. When ChREBP expression was silenced and SREBP-1c activation blocked simultaneously, glucose and insulin were still able to stimulated lipogenesis and lipogenic genes expression, and LXRα activation enhanced these effects, suggesting LXRα mediated directly glucose- and insulin-induced lipogenesis. In summary, glucose and insulin stimulated lipogenesis through both dissimilar and identical regulation pathway in porcine adipocytes. PMID:27871177

  16. Spectrin-ankyrin interaction mechanics: A key force balance factor in the red blood cell membrane skeleton.

    PubMed

    Saito, Masakazu; Watanabe-Nakayama, Takahiro; Machida, Shinichi; Osada, Toshiya; Afrin, Rehana; Ikai, Atsushi

    2015-01-01

    As major components of red blood cell (RBC) cytoskeleton, spectrin and F-actin form a network that covers the entire cytoplasmic surface of the plasma membrane. The cross-linked two layered structure, called the membrane skeleton, keeps the structural integrity of RBC under drastically changing mechanical environment during circulation. We performed force spectroscopy experiments on the atomic force microscope (AFM) as a means to clarify the mechanical characteristics of spectrin-ankyrin interaction, a key factor in the force balance of the RBC cytoskeletal structure. An AFM tip was functionalized with ANK1-62k and used to probe spectrin crosslinked to mica surface. A force spectroscopy study gave a mean unbinding force of ~30 pN under our experimental conditions. Two energy barriers were identified in the unbinding process. The result was related to the well-known flexibility of spectrin tetramer and participation of ankyrin 1-spectrin interaction in the overall balance of membrane skeleton dynamics.

  17. Pulmonary embolism associated with protein C deficiency and abuse of anabolic-androgen steroids.

    PubMed

    Alhadad, Alaa; Acosta, Stefan; Sarabi, Latif; Kölbel, Tilo

    2010-04-01

    We present the case of a 19-year-old male athlete with protein C deficiency who developed proximal deep venous thrombosis and pulmonary embolism while abusing anabolic-androgenic steroids. Anabolic-androgenic steroids have been reported to have anticoagulatory and profibrinolytic effects in patients with protein C deficiency. Despite these antithrombotic effects, the patient developed repeated venous thromboembolism during treatment with low-molecular-weight heparin. The net effect of anabolic-androgenic steroids on the haemostatic system may change from antithrombotic to prothrombotic in male abusers of anabolic steroids with protein C deficiency.

  18. [Successive ruptures of patellar and Achilles tendons. Anabolic steroids in competitive sports].

    PubMed

    Isenberg, J; Prokop, A; Skouras, E

    2008-01-01

    Derivatives of testosterone or of 19-nor-testosterone are used as anabolics for the purpose of improving performance although the effect of anabolics is known still to be under discussion. The use of anabolic steroids continues among competitive athletes despite increased controls and increasingly frequent dramatic incidents connected with them. Whereas metabolic dysfunction during anabolic use is well documented, ruptures of the large tendons are rarely reported. Within 18 months, a 29-year-old professional footballer needed surgery for rupture of the patellar tendon and of both Achilles tendons. Carefully directed questioning elicited confirmation that he had taken different anabolic steroids regularly for 3 years with the intention of improving his strength. After each operation anabolic steroids were taken again at a high dosage during early convalescence and training. Minimally invasive surgery and open suturing techniques led to complete union of the Achilles tendons in good time. Training and anabolic use (metenolon 300 mg per week) started early after suturing of the patellar tendon including bone tunnels culminated in histologically confirmed rerupture after 8 weeks. After a ligament reconstruction with a semitendinosus tendon graft with subsequent infection, the tendon and reserve traction apparatus were lost. Repeated warnings of impaired healing if anabolic use was continued had been given without success. In view of the high number of unrecorded cases in competitive and athletic sports, we can assume that the use of anabolic steroids is also of quantitative relevance in the operative treatment of tendon ruptures.

  19. A jaundiced bodybuilder Cholestatic hepatitis as side effect of injectable anabolic-androgenic steroids.

    PubMed

    Boks, Marije N; Tiebosch, Anton T; van der Waaij, Laurens A

    2016-12-12

    The use of anabolic steroids is prevalent in recreational athletes. This case report describes a young amateur bodybuilder who was referred to our outpatient clinic with jaundice and loss of appetite due to cholestatic hepatitis. Additional tests including a liver biopsy made it likely that the hepatitis was caused by the injectable anabolic steroid trenbolone enanthate. Cholestatic hepatitis may not be limited to the use of oral anabolic-androgenic steroids, as is widely assumed. Therefore, and because of other side effects, the recreational use of all forms of anabolic steroids should be discouraged.

  20. Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility

    SciTech Connect

    Dogan, Nergiz; Wu, Weisheng; Morrissey, Christapher S.; Chen, Kuan-Bei; Stonestrom, Aaron; Long, Maria; Keller, Cheryl A.; Cheng, Yong; Jain, Deepti; Visel, Axel; Pennacchio, Len A.; Weiss, Mitchell J.; Blobel, Gerd A.; Hardison, Ross C.

    2015-04-23

    Regulated gene expression controls organismal development, and variation in regulatory patterns has been implicated in complex traits. Thus accurate prediction of enhancers is important for further understanding of these processes. Genome-wide measurement of epigenetic features, such as histone modifications and occupancy by transcription factors, is improving enhancer predictions, but the contribution of these features to prediction accuracy is not known. Given the importance of the hematopoietic transcription factor TAL1 for erythroid gene activation, we predicted candidate enhancers based on genomic occupancy by TAL1 and measured their activity. Contributions of multiple features to enhancer prediction were evaluated based on the results of these and other studies. Results: TAL1-bound DNA segments were active enhancers at a high rate both in transient transfections of cultured cells (39 of 79, or 56%) and transgenic mice (43 of 66, or 65%). The level of binding signal for TAL1 or GATA1 did not help distinguish TAL1-bound DNA segments as active versus inactive enhancers, nor did the density of regulation-related histone modifications. A meta-analysis of results from this and other studies (273 tested predicted enhancers) showed that the presence of TAL1, GATA1, EP300, SMAD1, H3K4 methylation, H3K27ac, and CAGE tags at DNase hypersensitive sites gave the most accurate predictors of enhancer activity, with a success rate over 80% and a median threefold increase in activity. Chromatin accessibility assays and the histone modifications H3K4me1 and H3K27ac were sensitive for finding enhancers, but they have high false positive rates unless transcription factor occupancy is also included. Conclusions: Occupancy by key transcription factors such as TAL1, GATA1, SMAD1, and EP300, along with evidence of transcription, improves the accuracy of enhancer predictions based on epigenetic features.

  1. Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility

    DOE PAGES

    Dogan, Nergiz; Wu, Weisheng; Morrissey, Christapher S.; ...

    2015-04-23

    Regulated gene expression controls organismal development, and variation in regulatory patterns has been implicated in complex traits. Thus accurate prediction of enhancers is important for further understanding of these processes. Genome-wide measurement of epigenetic features, such as histone modifications and occupancy by transcription factors, is improving enhancer predictions, but the contribution of these features to prediction accuracy is not known. Given the importance of the hematopoietic transcription factor TAL1 for erythroid gene activation, we predicted candidate enhancers based on genomic occupancy by TAL1 and measured their activity. Contributions of multiple features to enhancer prediction were evaluated based on the resultsmore » of these and other studies. Results: TAL1-bound DNA segments were active enhancers at a high rate both in transient transfections of cultured cells (39 of 79, or 56%) and transgenic mice (43 of 66, or 65%). The level of binding signal for TAL1 or GATA1 did not help distinguish TAL1-bound DNA segments as active versus inactive enhancers, nor did the density of regulation-related histone modifications. A meta-analysis of results from this and other studies (273 tested predicted enhancers) showed that the presence of TAL1, GATA1, EP300, SMAD1, H3K4 methylation, H3K27ac, and CAGE tags at DNase hypersensitive sites gave the most accurate predictors of enhancer activity, with a success rate over 80% and a median threefold increase in activity. Chromatin accessibility assays and the histone modifications H3K4me1 and H3K27ac were sensitive for finding enhancers, but they have high false positive rates unless transcription factor occupancy is also included. Conclusions: Occupancy by key transcription factors such as TAL1, GATA1, SMAD1, and EP300, along with evidence of transcription, improves the accuracy of enhancer predictions based on epigenetic features.« less

  2. Impaired inactivation of digestive proteases: The possible key factor for the high susceptibility of germ-free and antibiotic-treated animals to gut epithelial injury

    PubMed Central

    Qin, Xiaofa

    2017-01-01

    Recent study shows that germ-free and antibiotic-treated animals are highly susceptible to gut epithelial injury. This paper addresses that impaired inactivation of digestive proteases may be the key factor for the increased susceptibility. PMID:28251033

  3. Impaired inactivation of digestive proteases: The possible key factor for the high susceptibility of germ-free and antibiotic-treated animals to gut epithelial injury.

    PubMed

    Qin, Xiaofa

    2017-02-15

    Recent study shows that germ-free and antibiotic-treated animals are highly susceptible to gut epithelial injury. This paper addresses that impaired inactivation of digestive proteases may be the key factor for the increased susceptibility.

  4. New Evidences of Key Factors Involved in "Silent Stones" Etiopathogenesis and Trace Elements: Microscopic, Spectroscopic, and Biochemical Approach.

    PubMed

    Cavalu, Simona; Popa, Adriana; Bratu, Ioan; Borodi, Gheorghe; Maghiar, Adrian

    2015-12-01

    The knowledge of the key factors involved in etiopathogenesis of the gallstone disease requires chemical, structural, and elemental composition analysis. The application of different complementary analytical techniques, both microscopic and spectroscopic, are aimed to provide a more comprehensive determination of the gallbladder calculi ultrastructure and trace element identification. High sensitivity techniques such as electron microscopy (SEM), Fourier transform infrared (FTIR), electron paramagnetic resonance (EPR) spectroscopy, and X-ray diffraction (XRD) along with biochemical analysis are used in a new attempt to investigate various factors which play a regulatory role in the pathogenesis of gallstones. The microstructure of different types of gallbladder stones has specific characteristics which are related to the elemental composition. The binding of metal ions with bile salts and bilirubin plays important roles in gallstone formation as revealed by FTIR spectrum of calcium bilirubinate complex in pigment gallstones. The EPR results demonstrated the generation of bilirubin free radicals and variation of its electronic structure and conjugation system in the skeleton of bilirubin molecule during complex formation. EPR spectra of pigment gallstones demonstrate the coexistence of four paramagnetic centers including stable bilirubin free radical, Mn2+, Cu2+, and Fe3+ with distinct magnetic parameters and well-resolved hyperfine structure in the case of Mn2+ ions. The result confirms a macromolecular network structure with proteins and the formation of bilirubin-coordinated polymer. Bilirubin and bilirubinate free radical complexes may play an important role in pigment gallstone formation.

  5. Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma

    PubMed Central

    Kreher, Stephan; Bouhlel, M. Amine; Cauchy, Pierre; Lamprecht, Björn; Li, Shuang; Grau, Michael; Hummel, Franziska; Köchert, Karl; Anagnostopoulos, Ioannis; Jöhrens, Korinna; Hummel, Michael; Hiscott, John; Wenzel, Sören-Sebastian; Lenz, Peter; Schneider, Markus; Küppers, Ralf; Scheidereit, Claus; Giefing, Maciej; Siebert, Reiner; Rajewsky, Klaus; Lenz, Georg; Cockerill, Peter N.; Janz, Martin; Dörken, Bernd; Bonifer, Constanze; Mathas, Stephan

    2014-01-01

    Deregulated transcription factor (TF) activities are commonly observed in hematopoietic malignancies. Understanding tumorigenesis therefore requires determining the function and hierarchical role of individual TFs. To identify TFs central to lymphomagenesis, we identified lymphoma type-specific accessible chromatin by global mapping of DNaseI hypersensitive sites and analyzed enriched TF-binding motifs in these regions. Applying this unbiased approach to classical Hodgkin lymphoma (HL), a common B-cell–derived lymphoma with a complex pattern of deregulated TFs, we discovered interferon regulatory factor (IRF) sites among the top enriched motifs. High-level expression of the proinflammatory TF IRF5 was specific to HL cells and crucial for their survival. Furthermore, IRF5 initiated a regulatory cascade in human non-Hodgkin B-cell lines and primary murine B cells by inducing the TF AP-1 and cooperating with NF-κB to activate essential characteristic features of HL. Our strategy efficiently identified a lymphoma type-specific key regulator and uncovered a tumor promoting role of IRF5. PMID:25288773

  6. Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma.

    PubMed

    Kreher, Stephan; Bouhlel, M Amine; Cauchy, Pierre; Lamprecht, Björn; Li, Shuang; Grau, Michael; Hummel, Franziska; Köchert, Karl; Anagnostopoulos, Ioannis; Jöhrens, Korinna; Hummel, Michael; Hiscott, John; Wenzel, Sören-Sebastian; Lenz, Peter; Schneider, Markus; Küppers, Ralf; Scheidereit, Claus; Giefing, Maciej; Siebert, Reiner; Rajewsky, Klaus; Lenz, Georg; Cockerill, Peter N; Janz, Martin; Dörken, Bernd; Bonifer, Constanze; Mathas, Stephan

    2014-10-21

    Deregulated transcription factor (TF) activities are commonly observed in hematopoietic malignancies. Understanding tumorigenesis therefore requires determining the function and hierarchical role of individual TFs. To identify TFs central to lymphomagenesis, we identified lymphoma type-specific accessible chromatin by global mapping of DNaseI hypersensitive sites and analyzed enriched TF-binding motifs in these regions. Applying this unbiased approach to classical Hodgkin lymphoma (HL), a common B-cell-derived lymphoma with a complex pattern of deregulated TFs, we discovered interferon regulatory factor (IRF) sites among the top enriched motifs. High-level expression of the proinflammatory TF IRF5 was specific to HL cells and crucial for their survival. Furthermore, IRF5 initiated a regulatory cascade in human non-Hodgkin B-cell lines and primary murine B cells by inducing the TF AP-1 and cooperating with NF-κB to activate essential characteristic features of HL. Our strategy efficiently identified a lymphoma type-specific key regulator and uncovered a tumor promoting role of IRF5.

  7. Identification of HNF-4α as a key transcription factor to promote ChREBP expression in response to glucose

    PubMed Central

    Meng, Jian; Feng, Ming; Dong, Weibing; Zhu, Yemin; Li, Yakui; Zhang, Ping; Wu, Lifang; Li, Minle; Lu, Ying; Chen, Hanbei; Liu, Xing; Lu, Yan; Sun, Haipeng; Tong, Xuemei

    2016-01-01

    Transcription factor carbohydrate responsive element binding protein (ChREBP) promotes glycolysis and lipogenesis in metabolic tissues and cancer cells. ChREBP-α and ChREBP-β, two isoforms of ChREBP transcribed from different promoters, are both transcriptionally induced by glucose. However, the mechanism by which glucose increases ChREBP mRNA levels remains unclear. Here we report that hepatocyte nuclear factor 4 alpha (HNF-4α) is a key transcription factor for glucose-induced ChREBP-α and ChREBP-β expression. Ectopic HNF-4α expression increased ChREBP transcription while knockdown of HNF-4α greatly reduced ChREBP mRNA levels in liver cancer cells and mouse primary hepatocytes. HNF-4α not only directly bound to an E-box-containing region in intron 12 of the ChREBP gene, but also promoted ChREBP-β transcription by directly binding to two DR1 sites and one E-box-containing site of the ChREBP-β promoter. Moreover, HNF-4α interacted with ChREBP-α and synergistically promoted ChREBP-β transcription. Functionally, HNF-4α suppression reduced glucose-dependent ChREBP induction. Increased nuclear abundance of HNF-4α and its binding to cis-elements of ChREBP gene in response to glucose contributed to glucose-responsive ChREBP transcription. Taken together, our results not only revealed the novel mechanism by which HNF-4α promoted ChREBP transcription in response to glucose, but also demonstrated that ChREBP-α and HNF-4α synergistically increased ChREBP-β transcription. PMID:27029511

  8. Screening active components from Yu-ping-feng-san for regulating initiative key factors in allergic sensitization.

    PubMed

    Shen, Dandan; Xie, Xuejian; Zhu, Zhijie; Yu, Xi; Liu, Hailiang; Wang, Huizhu; Fan, Hongwei; Wang, Dawei; Jiang, Guorong; Hong, Min

    2014-01-01

    Yu-ping-feng-san (YPFS) is a Chinese medical formula that is used clinically for allergic diseases and characterized by reducing allergy relapse. Our previous studies demonstrated that YPFS efficiently inhibited T helper 2 cytokines in allergic inflammation. The underlying mechanisms of action of YPFS and its effective components remain unclear. In this study, it was shown that YPFS significantly inhibited production of thymic stromal lymphopoietin (TSLP), an epithelial cell-derived initiative factor in allergic inflammation, in vitro and in vivo. A method of human bronchial epithelial cell (16HBE) binding combined with HPLC-MS (named 16HBE-HPLC-MS) was established to explore potential active components of YPFS. The following five components bound to 16HBE cells: calycosin-7-glucoside, ononin, claycosin, sec-o-glucosylhamaudol and formononetin. Serum from YPFS-treated mice was analyzed and three major components were detected claycosin, formononetin and cimifugin. Among these, claycosin and formononetin were detected by 16HBE-HPLC-MS and in the serum of YPFS-treated mice. Claycosin and formononetin decreased the level of TSLP markedly at the initial stage of allergic inflammation in vivo. Nuclear factor (NF)-κB, a key transcription factor in TSLP production, was also inhibited by claycosin and formononetin, either in terms of transcriptional activation or its nuclear translocation in vitro. Allergic inflammation was reduced by claycosin and formononetin when they are administered only at the initial stage in a murine model of atopic contact dermatitis. Thus, epithelial cell binding combined with HPLC-MS is a valid method for screening active components from complex mixtures of Chinese medicine. It was demonstrated that the compounds screened from YPFS significantly attenuated allergic inflammation probably by reducing TSLP production via regulating NF-κB activation.

  9. Bombyx mori P-element Somatic Inhibitor (BmPSI) Is a Key Auxiliary Factor for Silkworm Male Sex Determination

    PubMed Central

    Chen, Shuqing; Zeng, Baosheng; James, Anthony A.; Tan, Anjiang; Huang, Yongping

    2017-01-01

    Manipulation of sex determination pathways in insects provides the basis for a wide spectrum of strategies to benefit agriculture and public health. Furthermore, insects display a remarkable diversity in the genetic pathways that lead to sex differentiation. The silkworm, Bombyx mori, has been cultivated by humans as a beneficial insect for over two millennia, and more recently as a model system for studying lepidopteran genetics and development. Previous studies have identified the B. mori Fem piRNA as the primary female determining factor and BmMasc as its downstream target, while the genetic scenario for male sex determination was still unclear. In the current study, we exploite the transgenic CRISPR/Cas9 system to generate a comprehensive set of knockout mutations in genes BmSxl, Bmtra2, BmImp, BmImpM, BmPSI and BmMasc, to investigate their roles in silkworm sex determination. Absence of Bmtra2 results in the complete depletion of Bmdsx transcripts, which is the conserved downstream factor in the sex determination pathway, and induces embryonic lethality. Loss of BmImp or BmImpM function does not affect the sexual differentiation. Mutations in BmPSI and BmMasc genes affect the splicing of Bmdsx and the female reproductive apparatus appeared in the male external genital. Intriguingly, we identify that BmPSI regulates expression of BmMasc, BmImpM and Bmdsx, supporting the conclusion that it acts as a key auxiliary factor in silkworm male sex determination. PMID:28103247

  10. Geminin deletion increases the number of fetal hematopoietic stem cells by affecting the expression of key transcription factors.

    PubMed

    Karamitros, Dimitris; Patmanidi, Alexandra L; Kotantaki, Panoraia; Potocnik, Alexandre J; Bähr-Ivacevic, Tomi; Benes, Vladimir; Lygerou, Zoi; Kioussis, Dimitris; Taraviras, Stavros

    2015-01-01

    Balancing stem cell self-renewal and initiation of lineage specification programs is essential for the development and homeostasis of the hematopoietic system. We have specifically ablated geminin in the developing murine hematopoietic system and observed profound defects in the generation of mature blood cells, leading to embryonic lethality. Hematopoietic stem cells (HSCs) accumulated in the fetal liver following geminin ablation, while committed progenitors were reduced. Genome-wide transcriptome analysis identified key HSC transcription factors as being upregulated upon geminin deletion, revealing a gene network linked with geminin that controls fetal hematopoiesis. In order to obtain mechanistic insight into the ability of geminin to regulate transcription, we examined Hoxa9 as an example of a key gene in definitive hematopoiesis. We demonstrate that in human K562 cells geminin is associated with HOXA9 regulatory elements and its absence increases HOXA9 transcription similarly to that observed in vivo. Moreover, silencing geminin reduced recruitment of the PRC2 component SUZ12 to the HOXA9 locus and resulted in an increase in RNA polymerase II recruitment and H3K4 trimethylation (H3K4me3), whereas the repressive marks H3K9me3 and H3K27me3 were reduced. The chromatin landscape was also modified at the regulatory regions of HOXA10 and GATA1. K562 cells showed a reduced ability to differentiate to erythrocytes and megakaryocytes upon geminin silencing. Our data suggest that geminin is indispensable for fetal hematopoiesis and regulates the generation of a physiological pool of stem and progenitor cells in the fetal hematopoietic system.

  11. Supplemental dietary leucine and the skeletal muscle anabolic response to essential amino acids.

    PubMed

    Pasiakos, Stefan M; McClung, James P

    2011-09-01

    Skeletal muscle protein synthesis (MPS) is regulated by a number of dietary factors, to include essential amino acids (EAAs). Leucine, a branched-chain amino acid, has been identified as a stimulator of MPS in many cell culture and animal studies. However, whether supplemental leucine exerts a unique stimulatory effect, as compared to other EAAs, on muscle anabolism in humans has not been clearly demonstrated. A recent study found no improvement in resting MPS in adults who consumed a 10 g EAA supplement providing added leucine (3.5 g leucine) when compared to a control 10 g EAA supplement (1.8 g leucine). These findings suggest that added leucine is unnecessary for the stimulation of MPS when sufficient EAAs are provided; however, the study of supplemental leucine during conditions such as endurance exercise, caloric deprivation, and ageing may be warranted.

  12. Carotenoid derivatives inhibit nuclear factor kappa B activity in bone and cancer cells by targeting key thiol groups.

    PubMed

    Linnewiel-Hermoni, Karin; Motro, Yair; Miller, Yifat; Levy, Joseph; Sharoni, Yoav

    2014-10-01

    Aberrant activation of the nuclear factor kappa B (NFkB) transcription system contributes to cancer progression, and has a harmful effect on bone health. Several major components of the NFkB pathway such as IkB Kinase (IKK) and the NFkB subunits contain cysteine residues that are critical for their activity. The interaction of electrophiles with these cysteine residues results in NFkB inhibition. Carotenoids, hydrophobic plant pigments, are devoid of electrophilic groups, and we have previously demonstrated that carotenoid derivatives, but not the native compounds activate the Nrf2 transcription system. The aim of the current study was to examine whether carotenoid derivatives inhibit NFkB, and, if so, to determine the molecular mechanism underpinning the inhibitory action. We report in the present study that a mixture of oxidized derivatives, prepared by ethanol extraction from partially oxidized lycopene preparation, inhibited NFkB reporter gene activity. In contrast, the intact carotenoid was inactive. A series of synthetic dialdehyde carotenoid derivatives inhibited reporter activity as well as several stages of the NFkB pathway in both cancer and bone cells. The activity of the carotenoid derivatives depended on the reactivity of the electrophilic groups in reactions such as Michael addition to sulfhydryl groups of proteins. Specifically, carotenoid derivatives directly interacted with two key proteins of the NFkB pathway: the IKKβ and the p65 subunit. Direct interaction with IKKβ was found in an in vitro kinase assay with a recombinant enzyme. The inhibition by carotenoid derivatives of p65 transcriptional activity was observed in a reporter gene assay performed in the presence of excess p65. This inhibition action resulted, at least in part, from direct interaction of the carotenoid derivative with p65 leading to reduced binding of the protein to DNA as evidenced by electrophoretic mobility shift assay (EMSA) experiments. Importantly, we found by using

  13. Bilateral deltoid myositis ossificans in a weightlifter using anabolic steroids.

    PubMed

    Schultzel, Mark M; Johnson, Michael H; Rosenthal, Howard G

    2014-09-01

    A 40-year-old male weightlifter presented with a 6-month history of a painless mass in the right deltoid. He had no history of trauma to the shoulder other than an arthroscopic rotator cuff repair a few weeks earlier. Physical examination showed a firm, nontender mass located longitudinally and coinciding with the deltoid, measuring 12×14×4 cm. There was no limitation in range of motion or functioning. Magnetic resonance imaging (MRI) and computed tomography (CT) scans suggested a lobulated, heterogeneous mass with multiple areas of calcification that raised suspicion for soft tissue sarcoma vs myositis ossificans. Marginal resection of the soft tissue mass was performed, and pathologic studies confirmed the diagnosis of xanthogranulomatous myositis ossificans with dystrophic calcifications and central cystic degeneration. At 2-week follow-up, the patient had improved range of motion and pain, but he noted a second soft tissue mass in the left deltoid. The MRI and CT scans showed a 10.5×16×3.4-cm linear, lobulated lesion with multiple calcifications, similar in appearance to the contralateral deltoid. The patient admitted to frequently injecting anabolic steroids into his deltoids. Because the patient was asymptomatic on the left side and the MRI appearance of the left deltoid mass was similar to that of the myositis ossificans seen on the right side, the patient opted for nonsurgical treatment. This is a rare case of myositis ossificans occurring bilaterally in the deltoids after repeated injections of anabolic steroids. There is currently no known association between anabolic steroids and myositis ossificans. This condition often mimics malignant neoplasms, illustrating the necessity of resection for diagnostic confirmation.

  14. [Use and abuse of androgens and anabolic steroids].

    PubMed

    Alén, M

    1993-01-01

    At therapeutic dosages, androgen and anabolic steroids enhance neither muscle strength nor competitive performance. Endogenous androgen secretion is inhibited, and the net effect is negligible. The dosages taken by athletes and body-builders are 10-50 fold greater than the therapeutic dosages, and give rise to hyperandrogenic conditions. Although this improves endurance, strength and muscle development, at the same time a manifest hormone disturbance is developed with a variety of consequences. Abusers, who as a rule inject illicit preparations themselves, are also at risk of hepatitis and HIV.

  15. Identification of Key Factors Involved in the Biosorption of Patulin by Inactivated Lactic Acid Bacteria (LAB) Cells

    PubMed Central

    Wang, Ling; Wang, Zhouli; Yuan, Yahong; Cai, Rui; Niu, Chen; Yue, Tianli

    2015-01-01

    The purpose of this study was to identify the key factors involved in patulin adsorption by heat-inactivated lactic acid bacteria (LAB) cells. For preventing bacterial contamination, a sterilization process was involved in the adsorption process. The effects of various physical, chemical, and enzymatic pre-treatments, simultaneous treatments, and post-treatments on the patulin adsorption performances of six LAB strains were evaluated. The pre-treated cells were characterized by scanning electron microscopy (SEM). Results showed that the removal of patulin by viable cells was mainly based on adsorption or degradation, depending on the specific strain. The adsorption abilities were widely increased by NaOH and esterification pre-treatments, and reduced by trypsin, lipase, iodate, and periodate pre-treatments. Additionally, the adsorption abilities were almost maintained at pH 2.2–4.0, and enhanced significantly at pH 4.0–6.0. The effects of sodium and magnesium ions on the adsorption abilities at pH 4 were slight and strain-specific. A lower proportion of patulin was released from the strain with higher adsorption ability. Analyses revealed that the physical structure of peptidoglycan was not a principal factor. Vicinal OH and carboxyl groups were not involved in patulin adsorption, while alkaline amino acids, thiol and ester compounds were important for patulin adsorption. Additionally, besides hydrophobic interaction, electrostatic interaction also participated in patulin adsorption, which was enhanced with the increase in pH (4.0–6.0). PMID:26581099

  16. Determination of key environmental factors responsible for distribution patterns of fiddler crabs in a tropical mangrove ecosystem.

    PubMed

    Mokhtari, Mohammad; Ghaffar, Mazlan Abd; Usup, Gires; Cob, Zaidi Che

    2015-01-01

    In tropical regions, different species of fiddler crabs coexist on the mangrove floor, which sometimes makes it difficult to define species-specific habitat by visual inspection. The aim of this study is to find key environmental parameters which affect the distribution of fiddler crabs and to determine the habitats in which each species was most abundant. Crabs were collected from 19 sites within the mudflats of Sepang-Lukut mangrove forest. Temperature, porewater salinity, organic matter, water content, carbon and nitrogen content, porosity, chlorophyll content, pH, redox potential, sediment texture and heavy metals were determined in each 1 m2 quadrate. Pearson correlation indicated that all sediment properties except pH and redox potential were correlated with sediment grain size. Canonical correspondence analysis (CCA) indicated that Uca paradussumieri was negatively correlated with salinity and redox potential. Sand dwelling species, Uca perplexa and Uca annulipes, were highly dependent on the abundance of 250 μm and 150 μm grain size particles in the sediment. Canonical Discriminative Analysis (CDA) indicated that variation in sediment grain size best explained where each crab species was most abundant. Moreover, U. paradussumieri commonly occupies muddy substrates of low shore, while U. forcipata lives under the shade of mangrove trees. U. annulipes and U. perplexa with the high number of spoon tipped setae on their second maxiliped are specialized to feed on the sandy sediments. U. rosea and U. triangularis are more common on muddy sediment with high sediment density. In conclusion, sediment grain size that influences most sediment properties acts as a main factor responsible for sediment heterogeneity. In this paper, the correlation between fiddler crab species and environmental parameters, as well as the interaction between sediment characteristics, was explained in order to define the important environmental factors in fiddler crab distributions.

  17. Improving the efficiency of isolated microspore culture in six-row spring barley: I-optimization of key physical factors.

    PubMed

    Esteves, Patricio; Belzile, François

    2014-06-01

    An improved isolated microspore culture protocol alleviating the recalcitrance typically observed in six-row spring barley was developed by optimizing four key physical factors to increase embryogenesis and reduce albinism. Doubled haploid (DH) plants are completely homozygous individuals that can be generated in just a few months via androgenesis in vitro. DHs are useful tools in genetic research and in plant breeding. Isolated microspore culture (IMC) is the most efficient way to produce DHs, but a strong genotype dependency imposes limitations to its wide application. Six-row, spring barley genotypes are considered as particularly recalcitrant due to a low frequency of embryogenesis and a high rate of albinism. Seeking to develop an efficient IMC protocol for this type of barley, we explored four important factors: (1) the harvest stage of immature spikes, (2) the type of pretreatment applied, (3) the osmotic potential in the induction medium, and (4) the plating density of microspores. This work was first performed using four barley genotypes: two typical six-row spring cultivars (ACCA and Léger), a two-row spring (Gobernadora) and a two-row winter (Igri) cultivar. First, by optimizing the harvest stage for each genotype we obtained a twofold to fourfold increase in the yield of embryogenic microspores. Second, two pretreatments (0.3 M mannitol for 2 days, or a combination of cold and heat over 15 days) both performed significantly better than the commonly used cold pretreatment (28 days at 4 °C). Third, an induction medium-containing mannitol (32 g/l) doubled green plant regeneration. Fourth, a plating density of 10(6) microspores/ml yielded the highest number of green regenerated plants. Our most important findings were then confirmed using sets of F1s from a six-row, spring-type breeding program.

  18. Receptor Activator for Nuclear Factor kappa B Ligand (RANKL) as an osteoimmune key regulator in bone physiology and pathology.

    PubMed

    Narducci, Paola; Bareggi, Renato; Nicolin, Vanessa

    2011-02-01

    The strength and integrity of the human skeleton depends on a delicate equilibrium between bone resorption and bone formation. Bone resorption is an elementary cellular activity in the modelling of the skeleton during growth and development. Later in life a most important physiological process in the skeleton is bone remodelling, which is locally initiated by resorption. During remodelling bone resorption is coupled to new bone formation that ensures renewal of bone with only minor local and temporary bone loss. Cells responsible for bone resorption and subsequent bone formation are the osteoclasts and osteoblasts, respectively. The osteoclast is derived from the pluripotent hematopoietic stem cell, which gives rise to a myeloid stem cell that can further differentiate into megakaryocytes, granulocytes, monocytes/macrophages and osteoclasts. The respective bone resorbing and forming actions of osteoclasts and osteoblasts are finely coupled, so that bone mass remains remarkably stable in a healthy adult. Imbalance between osteoclast and osteoblast activities can arise from a wide variety of hormonal changes or perturbations of inflammatory and growth factors resulting in postmenopausal osteoporosis, Paget's disease, lytic bone metastases, or rheumatoid arthritis, leading to increased bone resorption and crippling bone damage. In view of the critical role of osteoclasts in diverse pathology, there has been immense effort aimed at understanding the biology of this unique cell. The present review is focused on the current knowledge of the mechanisms that regulate the functional links between bone turnover and the immune system helping us to understand the main factors that lead to bone loss observed in osteoporosis, cancer and in rheumatoid arthritis. The aim of this review paper is to consider the key molecular interactions involved in the formation of osteoclast cells in normal and pathological conditions.

  19. Anabolic androgenic steroids, an easily forgotten cause of polycythaemia and cerebral infarction.

    PubMed

    Low, M S Y; Vilcassim, S; Fedele, P; Grigoriadis, G

    2016-04-01

    Excessive anabolic androgenic steroids (both exogenous and endogenous) are known causes of polycythaemia and ischaemic cardiovascular events. Despite this, they are commonly forgotten in the workup of patients. We report a case of exogenous anabolic androgenic steroid-induced polycythaemia and stroke and explore possible pitfalls for clinicians.

  20. 76 FR 72355 - Classification of Two Steroids, Prostanozol and Methasterone, as Schedule III Anabolic Steroids...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-23

    ... corticosteroids, treatment of delayed puberty in boys, treatment of metastatic breast cancer in women, and... stunted growth due to premature closure of the growth plates in long bones. In adolescent boys, anabolic steroid abuse can cause precocious sexual development. In both girls and women, anabolic steroid...

  1. Anabolic Steroids: A Threat to Body and Mind. National Institute on Drug Abuse Research Report Series.

    ERIC Educational Resources Information Center

    National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.

    This report, based on findings of recent studies on the use of anabolic steroids in the United States, was written to educate the public about these drugs and the dangers of misusing them. It notes that the nonmedical use of anabolic/androgenic steroids among adolescents and young adults is of growing concern, with possibly as many as half a…

  2. Systemic lupus erythematosus with membranous glomerulonephritis and transverse myelitis associated with anabolic steroid use.

    PubMed

    Radis, C D; Callis, K P

    1997-10-01

    This report describes a 29-year-old bodybuilder taking anabolic steroids who presented with urinary retention, arthralgias, and peripheral edema, subsequently developed acute lower-extremity paralysis, and was diagnosed as having transverse myelitis and membranous glomerulonephritis secondary to systemic lupus erythematosus (SLE). The association of anabolic steroid use and hyperprolactinemia, and their possible link to the development of SLE, are reviewed.

  3. Susceptibility to Phytophthora ramorum in a key infectious host: landscape variation in host genotype, host phenotype, and environmental factors.

    PubMed

    Anacker, Brian L; Rank, Nathan E; Hüberli, Daniel; Garbelotto, Matteo; Gordon, Sarah; Harnik, Tami; Whitkus, Richard; Meentemeyer, Ross

    2008-01-01

    Sudden oak death is an emerging forest disease caused by the invasive pathogen Phytophthora ramorum. Genetic and environmental factors affecting susceptibility to P. ramorum in the key inoculum-producing host tree Umbellularia californica (bay laurel) were examined across a heterogeneous landscape in California, USA. Laboratory susceptibility trials were conducted on detached leaves and assessed field disease levels for 97 host trees from 12 225-m(2) plots. Genotype and phenotype characteristics were assessed for each tree. Effects of plot-level environmental conditions (understory microclimate, amount of solar radiation and topographic moisture potential) on disease expression were also evaluated. Susceptibility varied significantly among U. californica trees, with a fivefold difference in leaf lesion size. Lesion size was positively related to leaf area, but not to other phenotypic traits or to field disease level. Genetic diversity was structured at three spatial scales, but primarily among individuals within plots. Lesion size was significantly related to amplified fragment length polymorphism (AFLP) markers, but local environment explained most variation in field disease level. Thus, substantial genetic variation in susceptibility to P. ramorum occurs in its principal foliar host U. californica, but local environment mediates expression of susceptibility in nature.

  4. Proton Gradients as a Key Physical Factor in the Evolution of the Forced Transport Mechanism Across the Lipid Membrane.

    PubMed

    Strbak, Oliver; Kanuchova, Zuzana; Krafcik, Andrej

    2016-11-01

    A critical phase in the transition from prebiotic chemistry to biological evolution was apparently an asymmetric ion flow across the lipid membrane. Due to imbalance in the ion flow, the early lipid vesicles could selectively take the necessary molecules from the environment, and release the side-products from the vesicle. Natural proton gradients played a definitively crucial role in this process, since they remain the basis of energy transfer in the present-day cells. On the basis of this supposition, and the premise of the early vesicle membrane's impermeability to protons, we have shown that the emergence of the proton gradient in the lipid vesicle could be a key physical factor in the evolution of the forced transport mechanism (pore formation and active transport) across the lipid bilayer. This driven flow of protons across the membrane is the result of the electrochemical proton gradient and osmotic pressures on the integrity of the lipid vesicle. At a critical number of new lipid molecules incorporated into the vesicle, the energies associated with the creation of the proton gradient exceed the bending stiffness of the lipid membrane, and overlap the free energy of the lipid bilayer pore formation.

  5. Research on key factors and their interaction effects of electromagnetic force of high-speed solenoid valve.

    PubMed

    Liu, Peng; Fan, Liyun; Hayat, Qaisar; Xu, De; Ma, Xiuzhen; Song, Enzhe

    2014-01-01

    Analysis consisting of numerical simulations along with lab experiments of interaction effects between key parameters on the electromagnetic force based on response surface methodology (RSM) has been also proposed to optimize the design of high-speed solenoid valve (HSV) and improve its performance. Numerical simulation model of HSV has been developed in Ansoft Maxwell environment and its accuracy has been validated through lab experiments. Effect of change of core structure, coil structure, armature structure, working air gap, and drive current on the electromagnetic force of HSV has been analyzed through simulation model and influence rules of various parameters on the electromagnetic force have been established. The response surface model of the electromagnetic force has been utilized to analyze the interaction effect between major parameters. It has been concluded that six interaction factors including working air gap with armature radius, drive current with armature thickness, coil turns with side pole radius, armature thickness with its radius, armature thickness with side pole radius, and armature radius with side pole radius have significant influence on the electromagnetic force. Optimal match values between coil turns and side pole radius; armature thickness and side pole radius; and armature radius and side pole radius have also been determined.

  6. TeA is a key virulence factor for Alternaria alternata (Fr.) Keissler infection of its host.

    PubMed

    Kang, Ye; Feng, Hongwei; Zhang, Jingxu; Chen, Shiguo; Valverde, Bernal E; Qiang, Sheng

    2017-03-04

    A toxin-deficient mutant strain, HP001 mutant of Alternaria alternata, whose mycelium is unable to infect its host, produces little tenuazonic acid (TeA) toxin. How TeA plays a role in initiating host infection by A. alternata remains unclear. In this research we use Imaging-PAM based on chlorophyll fluorescence parameters and transmission electron microscopy to explore the role of TeA toxin during the infection process of A. alternata. Photosystem II damage began even before wild type mycelium infected the leaves of its host, croftonweed (Ageratina adenophora). Compared with the wild type, HP001 mutant produces morphologically different colonies, hyphae with thinner cell walls, has higher reactive oxygen species (ROS) content and lower peroxidase activity, and fails to form appressoria on the host surface. Adding TeA toxin allows the mutant to partially recover these characters and more closely resemble the wild type. Additionally, we found that the mutant is able to elicit disease symptoms when its mycelium is placed on leaves whose epidermis has been manually removed, which indicates that TeA may be determinant in the fungus recognition of its plant host. Lack of TeA toxin appears responsible for the loss of pathogenicity of the HP001 mutant. As a key virulence factor, TeA toxin not only damages the host plant but also is involved in maintaining ROS content, host recognition, inducing appressoria to infect the host and for allowing completion of the infection process.

  7. Depression and key associated factors in female sex workers and women living with HIV/AIDS in the Dominican Republic.

    PubMed

    Rael, Christine T; Davis, Alissa

    2017-04-01

    Little is known about the mental health of female sex workers and women living with HIV/AIDS in the Dominican Republic, which impedes HIV prevention, testing, and treatment. This project estimates the prevalence of depression and identifies key contributing factors to this outcome in female sex workers, women living with HIV/AIDS, and a comparison group. Participants were female sex workers (N = 349), women living with HIV/AIDS (N = 213), and a comparison group of HIV-negative women who were not sex workers (N = 314) from the Dominican Republic. Participants completed questionnaires assessing demographic characteristics and depression. Female sex workers and women living with HIV/AIDS completed additional questionnaires ascertaining HIV or sex work-related internalized stigma. Depression was prevalent among female sex workers (70.2%), women living with HIV/AIDS (81.1%), and the comparison group (52.2%). Adjusted logistic regressions showed that internalized stigma was associated with depression for female sex workers (OR = 2.73; 95% CI = 1.95-3.84) and women living with HIV/AIDS (OR = 3.06; 95% CI = 1.86-5.05). Permanent income was associated with this outcome for female sex workers (OR = 0.08; 95% CI = 0.01-0.80) and the comparison group (OR = 0.04; 95% CI = 0.00-0.45).

  8. A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria

    PubMed Central

    Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2016-01-01

    Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens. DOI: http://dx.doi.org/10.7554/eLife.19605.001 PMID:27472897

  9. A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria.

    PubMed

    Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2016-07-29

    Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens.

  10. Deep sequencing of Lotus corniculatus L. reveals key enzymes and potential transcription factors related to the flavonoid biosynthesis pathway.

    PubMed

    Wang, Ying; Hua, Wenping; Wang, Jian; Hannoufa, Abdelali; Xu, Ziqin; Wang, Zhezhi

    2013-04-01

    Lotus corniculatus L. is used worldwide as a forage crop due to its abundance of secondary metabolites and its ability to grow in severe environments. Although the entire genome of L. corniculatus var. japonicus R. is being sequenced, the differences in morphology and production of secondary metabolites between these two related species have led us to investigate this variability at the genetic level, in particular the differences in flavonoid biosynthesis. Our goal is to use the resulting information to develop more valuable forage crops and medicinal materials. Here, we conducted Illumina/Solexa sequencing to profile the transcriptome of L. corniculatus. We produced 26,492,952 short reads that corresponded to 2.38 gigabytes of total nucleotides. These reads were then assembled into 45,698 unigenes, of which a large number associated with secondary metabolism were annotated. In addition, we identified 2,998 unigenes based on homology with L. japonicus transcription factors (TFs) and grouped them into 55 families. Meanwhile, a comparison of four tag-based digital gene expression libraries, built from the flowers, pods, leaves, and roots, revealed distinct patterns of spatial expression of candidate unigenes in flavonoid biosynthesis. Based on these results, we identified many key enzymes from L. corniculatus which were different from reference genes of L. japonicus, and five TFs that are potential enhancers in flavonoid biosynthesis. Our results provide initial genetics resources that will be valuable in efforts to manipulate the flavonoid metabolic pathway in plants.

  11. Research on Key Factors and Their Interaction Effects of Electromagnetic Force of High-Speed Solenoid Valve

    PubMed Central

    Fan, Liyun; Xu, De; Ma, Xiuzhen; Song, Enzhe

    2014-01-01

    Analysis consisting of numerical simulations along with lab experiments of interaction effects between key parameters on the electromagnetic force based on response surface methodology (RSM) has been also proposed to optimize the design of high-speed solenoid valve (HSV) and improve its performance. Numerical simulation model of HSV has been developed in Ansoft Maxwell environment and its accuracy has been validated through lab experiments. Effect of change of core structure, coil structure, armature structure, working air gap, and drive current on the electromagnetic force of HSV has been analyzed through simulation model and influence rules of various parameters on the electromagnetic force have been established. The response surface model of the electromagnetic force has been utilized to analyze the interaction effect between major parameters. It has been concluded that six interaction factors including working air gap with armature radius, drive current with armature thickness, coil turns with side pole radius, armature thickness with its radius, armature thickness with side pole radius, and armature radius with side pole radius have significant influence on the electromagnetic force. Optimal match values between coil turns and side pole radius; armature thickness and side pole radius; and armature radius and side pole radius have also been determined. PMID:25243217

  12. Identifying a key physical factor sensitive to the performance of Madden-Julian oscillation simulation in climate models

    NASA Astrophysics Data System (ADS)

    Kim, Go-Un; Seo, Kyong-Hwan

    2017-03-01

    A key physical factor in regulating the performance of Madden-Julian oscillation (MJO) simulation is examined by using 26 climate model simulations from the World Meteorological Organization's Working Group for Numerical Experimentation/Global Energy and Water Cycle Experiment Atmospheric System Study (WGNE and MJO-Task Force/GASS) global model comparison project. For this, intraseasonal moisture budget equation is analyzed and a simple, efficient physical quantity is developed. The result shows that MJO skill is most sensitive to vertically integrated intraseasonal zonal wind convergence (ZC). In particular, a specific threshold value of the strength of the ZC can be used as distinguishing between good and poor models. An additional finding is that good models exhibit the correct simultaneous convection and large-scale circulation phase relationship. In poor models, however, the peak circulation response appears 3 days after peak rainfall, suggesting unfavorable coupling between convection and circulation. For an improving simulation of the MJO in climate models, we propose that this delay of circulation in response to convection needs to be corrected in the cumulus parameterization scheme.

  13. Proton Gradients as a Key Physical Factor in the Evolution of the Forced Transport Mechanism Across the Lipid Membrane

    NASA Astrophysics Data System (ADS)

    Strbak, Oliver; Kanuchova, Zuzana; Krafcik, Andrej

    2016-11-01

    A critical phase in the transition from prebiotic chemistry to biological evolution was apparently an asymmetric ion flow across the lipid membrane. Due to imbalance in the ion flow, the early lipid vesicles could selectively take the necessary molecules from the environment, and release the side-products from the vesicle. Natural proton gradients played a definitively crucial role in this process, since they remain the basis of energy transfer in the present-day cells. On the basis of this supposition, and the premise of the early vesicle membrane's impermeability to protons, we have shown that the emergence of the proton gradient in the lipid vesicle could be a key physical factor in the evolution of the forced transport mechanism (pore formation and active transport) across the lipid bilayer. This driven flow of protons across the membrane is the result of the electrochemical proton gradient and osmotic pressures on the integrity of the lipid vesicle. At a critical number of new lipid molecules incorporated into the vesicle, the energies associated with the creation of the proton gradient exceed the bending stiffness of the lipid membrane, and overlap the free energy of the lipid bilayer pore formation.

  14. Plant NF-Y transcription factors: Key players in plant-microbe interactions, root development and adaptation to stress.

    PubMed

    Zanetti, María Eugenia; Rípodas, Carolina; Niebel, Andreas

    2016-12-08

    NF-Ys are heterotrimeric transcription factors composed by the NF-YA, NF-YB and NF-YC subunits. In plants, NF-Y subunits are encoded by multigene families whose members show structural and functional diversifications. An increasing number of NF-Y genes has been shown to play key roles during different stages of root nodule and arbuscular mycorrhizal symbiosis, as well as during the interaction of plants with pathogenic microorganisms. Individual members of the NF-YA and NF-YB families have also been implicated in the development of primary and lateral roots. In addition, different members of the NF-YA and NF-YB gene families from mono- and di-cotyledonous plants have been involved in plant responses to water and nutrient scarcity. This review presents the most relevant and striking results concerning these NF-Y subunits. A phylogenetic analysis of the functionally characterized NF-Y genes revealed that, across plant species, NF-Y proteins functioning in the same biological process tend to belong to common phylogenetic groups. Finally, we discuss the forthcoming challenges of plant NF-Y research, including the detailed dissection of expression patterns, the elucidation of functional specificities as well as the characterization of the potential NF-Y-mediated epigenetic mechanisms by which they control the expression of their target genes.

  15. Polyacrylamide grafted cellulose as an eco-friendly flocculant: Key factors optimization of flocculation to surfactant effluent.

    PubMed

    Zhu, Hangcheng; Zhang, Yong; Yang, Xiaogang; Shao, Lan; Zhang, Xiumei; Yao, Juming

    2016-01-01

    The discharge of effluents from surfactant manufacturers is giving rise to increasingly serious environmental problems. In order to develop the eco-friendly flocculation materials to achieve effective removal of pollutants from the surfactant effluents, the bamboo pulp cellulose from Phyllostachys heterocycla is employed as the skeleton material to synthesize an eco-friendly bamboo pulp cellulose-g-polyacrylamide (BPC-g-PAM) for flocculation. The BPC-g-PAM is used with the metal ions as the coagulant to treat the effluent from a surfactant manufacturer. The response surface methodology coupled with Box-behnken design is employed to optimize the key factors of coagulation-flocculation. The results show that the combination of Fe(3+) with BPC-g-PAM achieves the best coagulation-flocculation performance like, the fast treatment time, minimum coagulant and BPC-g-PAM dosages compared with the other two combinations of Al(3+) with BPC-g-PAM and Ca(2+) with BPC-g-PAM. Therefore, the combination of Fe(3+) with BPC-g-PAM is expected to promote its application for the pollution control in the surfactant manufacturers.

  16. Cytosolic chloride ion is a key factor in lysosomal acidification and function of autophagy in human gastric cancer cell.

    PubMed

    Hosogi, Shigekuni; Kusuzaki, Katsuyuki; Inui, Toshio; Wang, Xiangdong; Marunaka, Yoshinori

    2014-06-01

    The purpose of the present study was to clarify roles of cytosolic chloride ion (Cl(-) ) in regulation of lysosomal acidification [intra-lysosomal pH (pHlys )] and autophagy function in human gastric cancer cell line (MKN28). The MKN28 cells cultured under a low Cl(-) condition elevated pHlys and reduced the intra-lysosomal Cl(-) concentration ([Cl(-) ]lys ) via reduction of cytosolic Cl(-) concentration ([Cl(-) ]c ), showing abnormal accumulation of LC3II and p62 participating in autophagy function (dysfunction of autophagy) accompanied by inhibition of cell proliferation via G0 /G1 arrest without induction of apoptosis. We also studied effects of direct modification of H(+) transport on lysosomal acidification and autophagy. Application of bafilomycin A1 (an inhibitor of V-type H(+) -ATPase) or ethyl isopropyl amiloride [EIPA; an inhibitor of Na(+) /H(+) exchanger (NHE)] elevated pHlys and decreased [Cl(-) ]lys associated with inhibition of cell proliferation via induction of G0 /G1 arrest similar to the culture under a low Cl(-) condition. However, unlike low Cl(-) condition, application of the compound, bafilomycin A1 or EIPA, induced apoptosis associated with increases in caspase 3 and 9 without large reduction in [Cl(-) ]c compared with low Cl(-) condition. These observations suggest that the lowered [Cl(-) ]c primarily causes dysfunction of autophagy without apoptosis via dysfunction of lysosome induced by disturbance of intra-lysosomal acidification. This is the first study showing that cytosolic Cl(-) is a key factor of lysosome acidification and autophagy.

  17. Key Factors in the Rise of Mass Popular Education and Their Relevance for Education in Southern Africa in the Twenty-First Century.

    ERIC Educational Resources Information Center

    van Niekerk, E. J.

    This paper identifies the historical factors that played a key role in the rise of mass popular education and describes how these factors relate to education in Southern Africa in the 21st century. The broad overview of developments since the Renaissance begins with the Protestant Reformation, which established a theoretical basis for elementary…

  18. Screening the key microRNAs and transcription factors in prostate cancer based on microRNA functional synergistic relationships.

    PubMed

    Feng, Fan; Wu, Jitao; Gao, Zhenli; Yu, Shengqiang; Cui, Yuanshan

    2017-01-01

    Prostate cancer (PC) is a common neoplasm, and metastatic PC remains incurable. The study aims to screen key microRNAs (miRNAs) and transcription factors (TFs) involved in PC.The miRNA expression profile dataset (GSE45604) was downloaded from Gene Expression Omnibus database, including 50 PC and 10 normal specimens. Differentially expressed miRNAs (DEmiRNAs) were identified through limma package in R, and DEmiRNA-DEmiRNA co-regulation network was constructed based on the number of co-regulated target genes. Functional enrichment analysis of co-regulated target genes was performed using clusterProfiler package in R, and miRNA interactions sharing at least 1 functional term were used to construct a DEmiRNA-DEmiRNA functional synergistic network (MFSN). Based on Transcriptional Regulatory Element Database, cancer-related TFs which were co-regulated by DEmiRNAs were utilized to construct a DEmiRNA-TF regulation network.A total of 66 DEmiRNAs were identified, including 7 up-regulated miRNAs with 18,642 target genes and 59 down-regulated miRNAs with 130,694 target genes. Then, the DEmiRNA-DEmiRNA co-regulation network was constructed, including 66 DEmiRNAs and 2024 co-regulation relationships. In MFSN, hsa-miR-1184, hsa-miR-1207-5p, and hsa-miR-24 had significant functional synergistic relationships. The DEmiRNA-TF network contained 6 up-regulated DEmiRNAs and 4 of them were highlighted, as hsa-miR-1184, hsa-miR-1207-5p, hsa-miR-182, and hsa-miR-183. In subnetwork of the 4 miRNAs, peroxisome proliferative activated receptor, alpha (PPARA) and cyclic AMP-responsive element modulator (CREM) were the critical regulated TFs.Four up-regulated miRNAs (hsa-miR-1207-5p, hsa-miR-1184, hsa-miR-182, and hsa-miR-183) and 2 TFs (PPARA and CREM) were identified as key regulators in PC progression. The above 4 miRNAs might participate in PC progression by targeting PPARA and CREM.

  19. Screening the key microRNAs and transcription factors in prostate cancer based on microRNA functional synergistic relationships

    PubMed Central

    Feng, Fan; Wu, Jitao; Gao, Zhenli; Yu, Shengqiang; Cui, Yuanshan

    2017-01-01

    Abstract Prostate cancer (PC) is a common neoplasm, and metastatic PC remains incurable. The study aims to screen key microRNAs (miRNAs) and transcription factors (TFs) involved in PC. The miRNA expression profile dataset (GSE45604) was downloaded from Gene Expression Omnibus database, including 50 PC and 10 normal specimens. Differentially expressed miRNAs (DEmiRNAs) were identified through limma package in R, and DEmiRNA–DEmiRNA co-regulation network was constructed based on the number of co-regulated target genes. Functional enrichment analysis of co-regulated target genes was performed using clusterProfiler package in R, and miRNA interactions sharing at least 1 functional term were used to construct a DEmiRNA–DEmiRNA functional synergistic network (MFSN). Based on Transcriptional Regulatory Element Database, cancer-related TFs which were co-regulated by DEmiRNAs were utilized to construct a DEmiRNA–TF regulation network. A total of 66 DEmiRNAs were identified, including 7 up-regulated miRNAs with 18,642 target genes and 59 down-regulated miRNAs with 130,694 target genes. Then, the DEmiRNA–DEmiRNA co-regulation network was constructed, including 66 DEmiRNAs and 2024 co-regulation relationships. In MFSN, hsa-miR-1184, hsa-miR-1207-5p, and hsa-miR-24 had significant functional synergistic relationships. The DEmiRNA–TF network contained 6 up-regulated DEmiRNAs and 4 of them were highlighted, as hsa-miR-1184, hsa-miR-1207-5p, hsa-miR-182, and hsa-miR-183. In subnetwork of the 4 miRNAs, peroxisome proliferative activated receptor, alpha (PPARA) and cyclic AMP-responsive element modulator (CREM) were the critical regulated TFs. Four up-regulated miRNAs (hsa-miR-1207-5p, hsa-miR-1184, hsa-miR-182, and hsa-miR-183) and 2 TFs (PPARA and CREM) were identified as key regulators in PC progression. The above 4 miRNAs might participate in PC progression by targeting PPARA and CREM. PMID:28072703

  20. Parathyroid hormone 1-34 and skeletal anabolic action

    PubMed Central

    Sanghani, A.; Coathup, M.; Briggs, T.; Bostrom, M.; Blunn, G.

    2017-01-01

    Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect. Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1. PMID:28062525

  1. Research of stimulants and anabolic steroids in dietary supplements.

    PubMed

    Baume, N; Mahler, N; Kamber, M; Mangin, P; Saugy, M

    2006-02-01

    The purpose of this study was to analyze the composition of 103 dietary supplements bought on the internet. The supplements were dispatched in four different categories according to their announced contents [creatine, prohormones, "mental enhancers" and branched chain amino acids (BCAA)]. All the supplements were screened for the presence of stimulants and main anabolic steroids parent compounds. At the same time, the research was focused on the precursors and metabolites of testosterone and nandrolone. The study pointed out three products containing an anabolic steroid, metandienone, in a very high amount. The ingestion of such products induced a high quantity of metandienone metabolites in urines that would be considered as a positive antidoping test. The results have also shown that one creatine product and three "mental enhancers" contained traces of hormones or prohormones not claimed on the labels and 14 prohormone products contained substances other than those indicated by the manufacturer. The oral intake of the creatine product revealed the presence of the two main nandrolone metabolites (19-norandrosterone and 19-noretiocholanolone) in urine.

  2. Hormone Treatment and Muscle Anabolism during Aging: Androgens

    PubMed Central

    Dillon, E. Lichar; Durham, William J.; Urban, Randall J.; Sheffield-Moore, Melinda

    2010-01-01

    Aging is associated with a gradual decline in circulating testosterone concentrations and decreased musculature in men. While testosterone administration is often considered when symptoms of hypogonadism are presented, the long-term effects of androgen use on muscle physiology are not yet fully understood. The definition of hypogonadism in men remains obscure but is generally indicated by total testosterone concentrations less than a threshold value of 300-500 ng/dL. Androgen replacement therapy is generally safe in men and women with low endogenous testosterone concentrations. The development of selective androgen receptor modulators (SARMs) may provide additional options in treatment of hypogonadism while lowering the potential of side effects often associated with long-term androgen use. Androgen administration, either alone or in combination with other treatments, can be successful in improving muscle mass by increasing protein anabolism and reducing protein catabolism in men and women. Further research is necessary to optimize the anabolic and anticatabolic properties of androgens for treatment and prevention of muscle loss in men and women. PMID:20452103

  3. Effects of anabolic-androgens on brain reward function

    PubMed Central

    Mhillaj, Emanuela; Morgese, Maria G.; Tucci, Paolo; Bove, Maria; Schiavone, Stefania; Trabace, Luigia

    2015-01-01

    Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming androgen anabolic steroids (AAS). These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, their off-label utilization is very wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common. Symptoms of the chronic use of supra-therapeutic doses of AAS include anxiety, depression, aggression, paranoia, distractibility, confusion, amnesia. Interestingly, some studies have shown that AAS elicited electroencephalographic changes similar to those observed with amphetamine abuse. The frequency of side effects is higher among AAS abusers, with psychiatric complications such as labile mood, lack of impulse control and high violence. On the other hand, AAS addiction studies are complex because data collection is very difficult due to the subjects' reticence and can be biased by many variables, including physical exercise, that alter the reward system. Moreover, it has been reported that AAS may imbalance neurotransmitter systems involved in the reward process, leading to increased sensitivity toward opioid narcotics and central stimulants. The goal of this article is to review the literature on steroid abuse and changes to the reward system in preclinical and clinical studies. PMID:26379484

  4. In vitro vitamin K(2) and 1α,25-dihydroxyvitamin D(3) combination enhances osteoblasts anabolism of diabetic mice.

    PubMed

    Poon, Christina C W; Li, Rachel W S; Seto, Sai Wang; Kong, Siu Kai; Ho, Ho Pui; Hoi, Maggie P M; Lee, Simon M Y; Ngai, Sai Ming; Chan, Shun Wan; Leung, George P H; Kwan, Yiu Wa

    2015-11-15

    In this study, we evaluated the anabolic effect and the underlying cellular mechanisms involved of vitamin K2 (10 nM) and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) (10 nM), alone and in combination, on primary osteoblasts harvested from the iliac crests of C57BL/KsJ lean (+/+) and obese/diabetic (db/db) mice. A lower alkaline phosphatase (ALP) activity plus a reduced expression of bone anabolic markers and bone formation transcription factors (osteocalcin, Runx2, Dlx5, ATF4 and OSX) were consistently detected in osteoblasts of db/db mice compared to lean mice. A significantly higher calcium deposits formation in osteoblasts was observed in lean mice when compared to db/db mice. Co-administration of vitamin K2 (10 nM) and 1,25(OH)2D3 (10 nM) caused an enhancement of calcium deposits in osteoblasts in both strains of mice. Vitamins K2 and 1,25(OH)2D3 co-administration time-dependently (7, 14 and 21 days) increased the levels of bone anabolic markers and bone formation transcription factors, with a greater magnitude of increase observed in osteoblasts of db/db mice. Combined vitamins K2 plus 1,25(OH)2D3 treatment significantly enhanced migration and the re-appearance of surface microvilli and ruffles of osteoblasts of db/db mice. Thus, our results illustrate that vitamins K2 plus D3 combination could be a novel therapeutic strategy in treating diabetes-associated osteoporosis.

  5. Maintaining the momentum: Key factors influencing acceptance of influenza vaccination among pregnant women following the H1N1 pandemic

    PubMed Central

    Halperin, Beth A; MacKinnon-Cameron, Donna; McNeil, Shelly; Kalil, Jennifer; Halperin, Scott A

    2015-01-01

    This survey study compared pre- and post-pandemic knowledge, attitudes, beliefs, and intended behaviors of pregnant women regarding influenza vaccination (seasonal and/or pandemic) during pregnancy in order to determine key factors influencing their decision to adhere to influenza vaccine recommendations. Only 36% of 662 pre-pandemic respondents knew that influenza was more severe in pregnant women, compared to 62% of the 159 post-pandemic respondents. Of the pre-pandemic respondents, 41% agreed or strongly agreed that that it was safer to wait until after the first 3 months to receive the seasonal influenza vaccine, whereas 23% of the post-pandemic cohort agreed or strongly agreed; 32% of pre-pandemic participants compared to 11% of post-pandemic respondents felt it was best to avoid all vaccines while pregnant. Despite 61% of the pre-pandemic cohort stating that they would have the vaccine while pregnant if their doctor recommended it and 54% citing their doctor/nurse as their primary source of vaccine information, only 20% said their doctor discussed influenza vaccination during their pregnancy, compared to 77% of the post-pandemic respondents who reported having this conversation. Women whose doctors discussed influenza vaccine during pregnancy had higher overall knowledge scores (P < 0.0001; P = 0.005) and were more likely to believe the vaccine is safe in all stages of pregnancy (P < 0.0001; P = 0.001) than those whose doctors did not discuss influenza vaccination. The 2009 H1N1 pandemic experience appeared to change attitudes and behaviours of health care providers and their pregnant patients toward influenza vaccination. PMID:25668670

  6. Human CAP1 is a key factor in the recycling of cofilin and actin for rapid actin turnover.

    PubMed

    Moriyama, Kenji; Yahara, Ichiro

    2002-04-15

    Cofilin-ADF (actin-depolymerizing factor) is an essential driver of actin-based motility. We discovered two proteins, p65 and p55, that are components of the actin-cofilin complex in a human HEK293 cell extract and identified p55 as CAP1/ASP56, a human homologue of yeast CAP/SRV2 (cyclase-associated protein). CAP is a bifunctional protein with an N-terminal domain that binds to Ras-responsive adenylyl cyclase and a C-terminal domain that inhibits actin polymerization. Surprisingly, we found that the N-terminal domain of CAP1, but not the C-terminal domain, is responsible for the interaction with the actin-cofilin complex. The N-terminal domain of CAP1 was also found to accelerate the depolymerization of F-actin at the pointed end, which was further enhanced in the presence of cofilin and/or the C-terminal domain of CAP1. Moreover, CAP1 and its C-terminal domain were observed to facilitate filament elongation at the barbed end and to stimulate ADP-ATP exchange on G-actin, a process that regenerates easily polymerizable G-actin. Although cofilin inhibited the nucleotide exchange on G-actin even in the presence of the C-terminal domain of CAP1, its N-terminal domain relieved this inhibition. Thus, CAP1 plays a key role in speeding up the turnover of actin filaments by effectively recycling cofilin and actin and through its effect on both ends of actin filament.

  7. Characterization of key transcription factors as molecular signatures of HPV-positive and HPV-negative oral cancers.

    PubMed

    Verma, Gaurav; Vishnoi, Kanchan; Tyagi, Abhishek; Jadli, Mohit; Singh, Tejveer; Goel, Ankit; Sharma, Ankita; Agarwal, Kiran; Prasad, Subhash Chandra; Pandey, Durgatosh; Sharma, Shashi; Mehrotra, Ravi; Singh, Sukh Mahendra; Bharti, Alok Chandra

    2017-03-01

    Prior studies established constitutively active AP-1, NF-κB, and STAT3 signaling in oral cancer. Differential expression/activation of specific members of these transcription factors has been documented in HPV-positive oral lesions that respond better to therapy. We performed a comprehensive analysis of differentially expressed, transcriptionally active members of these pivotal signaling mediators to develop specific signatures of HPV-positive and HPV-negative oral lesions by immunohistochemical method that is applicable in low-resource settings. We examined a total of 31 prospective and 30 formalin-fixed, paraffin-embedded tissues from treatment-naïve, histopathologically and clinically confirmed cases diagnosed as oral or oropharyngeal squamous cell carcinoma (OSCC/OPSCC). Following determination of their HPV status by GP5 + /GP6 +  PCR, the sequential sections of the tissues were evaluated for expression of JunB, JunD, c-Fos, p50, p65, STAT3, and pSTAT3(Y705), along with two key regulatory proteins pEGFR and p16 by IHC. Independent analysis of JunB and p65 showed direct correlation with HPV positivity, whereas STAT3 and pSTAT3 were inversely correlated. A combined analysis of transcription factors revealed a more restrictive combination, characterized by the presence of AP-1 and NF-κB lacking involvement of STAT3 that strongly correlated with HPV-positive tumors. Presence of STAT3/pSTAT3 with NF-κB irrespective of the presence or absence of AP-1 members was present in HPV-negative lesions. Expression of pSTAT3 strongly correlated with all the AP-1/NF-κB members (except JunD), its upstream activator pEGFR(Y)(1092) , and HPV infection-related negative regulator p16. Overall, we show a simple combination of AP-1, NF-κB, and STAT3 members' expression that may serve as molecular signature of HPV-positive lesions or more broadly the tumors that show better prognosis.

  8. A large-scale, in vivo transcription factor screen defines bivalent chromatin as a key property of regulatory factors mediating Drosophila wing development.

    PubMed

    Schertel, Claus; Albarca, Monica; Rockel-Bauer, Claudia; Kelley, Nicholas W; Bischof, Johannes; Hens, Korneel; van Nimwegen, Erik; Basler, Konrad; Deplancke, Bart

    2015-04-01

    Transcription factors (TFs) are key regulators of cell fate. The estimated 755 genes that encode DNA binding domain-containing proteins comprise ∼ 5% of all Drosophila genes. However, the majority has remained uncharacterized so far due to the lack of proper genetic tools. We generated 594 site-directed transgenic Drosophila lines that contain integrations of individual UAS-TF constructs to facilitate spatiotemporally controlled misexpression in vivo. All transgenes were expressed in the developing wing, and two-thirds induced specific phenotypic defects. In vivo knockdown of the same genes yielded a phenotype for 50%, with both methods indicating a great potential for misexpression to characterize novel functions in wing growth, patterning, and development. Thus, our UAS-TF library provides an important addition to the genetic toolbox of Drosophila research, enabling the identification of several novel wing development-related TFs. In parallel, we established the chromatin landscape of wing imaginal discs by ChIP-seq analyses of five chromatin marks and RNA Pol II. Subsequent clustering revealed six distinct chromatin states, with two clusters showing enrichment for both active and repressive marks. TFs that carry such "bivalent" chromatin are highly enriched for causing misexpression phenotypes in the wing, and analysis of existing expression data shows that these TFs tend to be differentially expressed across the wing disc. Thus, bivalently marked chromatin can be used as a marker for spatially regulated TFs that are functionally relevant in a developing tissue.

  9. A large-scale, in vivo transcription factor screen defines bivalent chromatin as a key property of regulatory factors mediating Drosophila wing development

    PubMed Central

    Schertel, Claus; Albarca, Monica; Rockel-Bauer, Claudia; Kelley, Nicholas W.; Bischof, Johannes; Hens, Korneel

    2015-01-01

    Transcription factors (TFs) are key regulators of cell fate. The estimated 755 genes that encode DNA binding domain-containing proteins comprise ∼5% of all Drosophila genes. However, the majority has remained uncharacterized so far due to the lack of proper genetic tools. We generated 594 site-directed transgenic Drosophila lines that contain integrations of individual UAS-TF constructs to facilitate spatiotemporally controlled misexpression in vivo. All transgenes were expressed in the developing wing, and two-thirds induced specific phenotypic defects. In vivo knockdown of the same genes yielded a phenotype for 50%, with both methods indicating a great potential for misexpression to characterize novel functions in wing growth, patterning, and development. Thus, our UAS-TF library provides an important addition to the genetic toolbox of Drosophila research, enabling the identification of several novel wing development-related TFs. In parallel, we established the chromatin landscape of wing imaginal discs by ChIP-seq analyses of five chromatin marks and RNA Pol II. Subsequent clustering revealed six distinct chromatin states, with two clusters showing enrichment for both active and repressive marks. TFs that carry such “bivalent” chromatin are highly enriched for causing misexpression phenotypes in the wing, and analysis of existing expression data shows that these TFs tend to be differentially expressed across the wing disc. Thus, bivalently marked chromatin can be used as a marker for spatially regulated TFs that are functionally relevant in a developing tissue. PMID:25568052

  10. Tartaric acid in red wine as one of the key factors to induce superconductivity in FeTe0.8S0.2

    NASA Astrophysics Data System (ADS)

    Deguchi, Keita; Okuda, Tohru; Hara, Hiroshi; Demura, Satoshi; Watanabe, Tohru; Okazaki, Hiroyuki; Fujioka, Masaya; Denholme, Saleem James; Ozaki, Toshinori; Yamaguchi, Takahide; Takeya, Hiroyuki; Saito, Fumie; Hisamoto, Masashi; Takano, Yoshihiko

    2013-04-01

    We investigated the key factor of superconductivity in FeTe1-xSx induced by alcoholic beverages. To understand the reason why red wine shows larger shielding volume fraction than the other alcoholic beverages, the red wine dependence of superconductivity was performed. All the samples heated in red wine made from different grapes shows large shielding volume fraction compared with the samples heated in water and other alcoholic beverages. The shielding volume fraction of the red wine samples is proportional to the concentration of tartaric acid. We found that tartaric acid is one of the key factors to induce superconductivity in FeTe1-xSx.

  11. New Insights into the Role of Anabolic Interventions in Dialysis Patients with Protein Energy Wasting

    PubMed Central

    Dong, Jie; Ikizler, T. Alp

    2010-01-01

    Purpose of review Patients on maintenance dialysis commonly develop protein-energy wasting (PEW), which is associated with poor survival. There have been several advances in anabolic interventions aimed at improving PEW in these patients in recent years. Recent findings Oral or parenteral nutritional supplementation, especially if administered during dialysis, improves net protein anabolism in chronic hemodialysis (CHD) patients. These beneficial effects have been extended to long-term benefits in recent clinical trials. Resistance exercise, alone or combined with intradialytic oral nutrition supplementation also improves net protein balance in the acute setting although recent studies indicated a limited beneficial effect of long-term exercise alone on muscle protein accretion in CHD patients. Anabolic agents such as growth hormone and androgens have been shown to exert significant benefits on visceral protein stores, muscle mass and strength. Ghrelin, a hormone with combined orexigenic and anti-inflammatory effects, is a potential new nutritional intervention in maintenance dialysis patients. Summary Existing anabolic therapeutic strategies have proven to be effective in improving PEW in maintenance dialysis patients. Combined anabolic interventions and several new and established anabolic hormones represent as further promising nutritional interventions. Large-scale randomized controlled trials examining the effects of anabolic interventions on mortality and morbidity are still lacking. PMID:19713839

  12. Vasopressin differentially modulates aggression and anxiety in adolescent hamsters administered anabolic steroids.

    PubMed

    Morrison, Thomas R; Ricci, Lesley A; Melloni, Richard H

    2016-11-01

    Adolescent Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids display increased offensive aggression and decreased anxiety correlated with an increase in vasopressin afferent development, synthesis, and neural signaling within the anterior hypothalamus. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts as hamsters display decreased offensive aggression and increased anxiety correlated with a decrease in anterior hypothalamic vasopressin. This study investigated the hypothesis that alterations in anterior hypothalamic vasopressin neural signaling modulate behavioral shifting between adolescent anabolic/androgenic steroid-induced offensive aggression and anxiety. To test this, adolescent male hamsters were administered anabolic/androgenic steroids and tested for offensive aggression or anxiety following direct pharmacological manipulation of vasopressin V1A receptor signaling within the anterior hypothalamus. Blockade of anterior hypothalamic vasopressin V1A receptor signaling suppressed offensive aggression and enhanced general and social anxiety in hamsters administered anabolic/androgenic steroids during adolescence, effectively reversing the pattern of behavioral response pattern normally observed during the adolescent exposure period. Conversely, activation of anterior hypothalamic vasopressin V1A receptor signaling enhanced offensive aggression in hamsters exposed to anabolic/androgenic steroids during adolescence. Together, these findings suggest that the state of vasopressin neural development and signaling in the anterior hypothalamus plays an important role in behavioral shifting between aggression and anxiety following adolescent exposure to anabolic/androgenic steroids.

  13. The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1 receptor density and function.

    PubMed

    Struik, Dicky; Fadda, Paola; Zara, Tamara; Zamberletti, Erica; Rubino, Tiziana; Parolaro, Daniela; Fratta, Walter; Fattore, Liana

    2017-01-01

    Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CB1 receptor agonist WIN55,212-2 (WIN) in rats. Lister Hooded male rats were treated intramuscularly with nandrolone (15mg/kg) or vehicle for 14 consecutive days, and then allowed to self-administer WIN (12.5μg/kg/infusion) intravenously. After reaching stable drug intake, self-administration behavior was extinguished to examine drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Other behavioral parameters presumed to influence drug-taking and drug-seeking behaviors were examined to gain more insight into the behavioral specificity of nandrolone treatment. Finally, animals were sacrificed for analysis of CB1 receptor density and function in selected brain areas. We found that nandrolone-treated rats self-administered up to 2 times more cannabinoid than vehicle-treated rats, but behaved similarly to control rats when tested for drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Enhanced cannabinoid intake by nandrolone-treated rats was not accompanied by changes in locomotor activity, sensorimotor gating, or memory function. However, our molecular data show that after chronic WIN self-administration nandrolone-treated rats display altered CB1 receptor density and function in selected brain areas. We hypothesize that increased cannabinoid self-administration in nandrolone-treated rats results from a nandrolone-induced decrease in reward function, which rats seem to compensate by voluntarily increasing their cannabinoid intake. Altogether, our findings corroborate the hypothesis that chronic exposure to anabolic-androgenic steroids induces dysfunction of the reward pathway in rats and might represent a potential risk factor for abuse of

  14. Pregnancy-associated plasma protein-A modulates the anabolic effects of parathyroid hormone in mouse bone.

    PubMed

    Clifton, Kari B; Conover, Cheryl A

    2015-12-01

    Intermittent parathyroid hormone (PTH) is a potent anabolic therapy for bone, and several studies have implicated local insulin-like growth factor (IGF) signaling in mediating this effect. The IGF system is complex and includes ligands and receptors, as well as IGF binding proteins (IGFBPs) and IGFBP proteases. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloprotease expressed by osteoblasts in vitro that has been shown to enhance local IGF action through cleavage of inhibitory IGFBP-4. This study was set up to test two specific hypotheses: 1) Intermittent PTH treatment increases the expression of IGF-I, IGFBP-4 and PAPP-A in bone in vivo, thereby increasing local IGF activity. 2) In the absence of PAPP-A, local IGF activity and the anabolic effects of PTH on bone are reduced. Wild-type (WT) and PAPP-A knock-out (KO) mice were treated with 80 μg/kg human PTH 1-34 or vehicle by subcutaneous injection five days per week for six weeks. IGF-I, IGFBP-4 and PAPP-A mRNA expression in bone were significantly increased in response to PTH treatment. PTH treatment of WT mice, but not PAPP-A KO mice, significantly increased expression of an IGF-responsive gene. Bone mineral density (BMD), as measured by DEXA, was significantly decreased in femurs of PAPP-A KO compared to WT mice with PTH treatment. Volumetric BMD, as measured by pQCT, was significantly decreased in femoral midshaft (primarily cortical bone), but not metaphysis (primarily trabecular bone), of PAPP-A KO compared to WT mice with PTH treatment. These data suggest that stimulation of PAPP-A expression by intermittent PTH treatment contributes to PTH bone anabolism in mice.

  15. In silico investigations of potential anabolic treatments in multiple myeloma-induced bone disease.

    PubMed

    Wang, Yan; Lin, Bo

    2013-07-01

    No anabolic drugs are currently approved to treat multiple myeloma (MM)-induced bone disease and the anti-MM agent bortezomib exhibits the anabolic effects in the clinic. In this study, we focus on investigating potential anabolic treatments of MM-induced bone disease using our previously proposed MM-bone model, with the goal for clarifying the underlying molecular/cellular mechanisms. Firstly, a variety of virtual drug treatments are explored by the parametric study to clarify the anabolic-related molecular/cellular mechanisms. The real drug (i.e., bortezomib) treatments are further examined by developing an integrated model with bortezomib to validate the clarified anabolic-related molecular/cellular mechanisms. The simulated responses to the bortezomib treatments that are validated by the clinical data are consistent with the simulated responses to the virtual drug treatments. Our study clarifies that the anabolic effects in the treatment of MM-induced bone disease are associated with promoting the differentiation of bone marrow stromal cells (BMSC) and inhibiting the apoptosis of active osteoblasts, while promoting the differentiation of osteoblast precursors is instead suggested to be associated with the anti-catabolic effects. Compared with the individual anabolic therapies, the anabolic therapies that promote the differentiation of BMSC in combination with the anti-MM/anti-catabolic therapies are found to induce a greater increase in the bone volume, while the anabolic therapies that inhibit the apoptosis of active osteoblasts in combination with the anti-MM/anti-catabolic therapies induce a lower increase in the bone volume. The simulations also suggest that the direct inhibition of bortezomib on the osteoclast activity is probably a redundant mechanism.

  16. Key design factors affecting microbial community composition and pathogenic organism removal in horizontal subsurface flow constructed wetlands.

    PubMed

    Morató, Jordi; Codony, Francesc; Sánchez, Olga; Pérez, Leonardo Martín; García, Joan; Mas, Jordi

    2014-05-15

    Constructed wetlands constitute an interesting option for wastewater reuse since high concentrations of contaminants and pathogenic microorganisms can be removed with these natural treatment systems. In this work, the role of key design factors which could affect microbial removal and wetland performance, such as granular media, water depth and season effect was evaluated in a pilot system consisting of eight parallel horizontal subsurface flow (HSSF) constructed wetlands treating urban wastewater from Les Franqueses del Vallès (Barcelona, Spain). Gravel biofilm as well as influent and effluent water samples of these systems were taken in order to detect the presence of bacterial indicators such as total coliforms (TC), Escherichia coli, fecal enterococci (FE), Clostridium perfringens, and other microbial groups such as Pseudomonas and Aeromonas. The overall microbial inactivation ratio ranged between 1.4 and 2.9 log-units for heterotrophic plate counts (HPC), from 1.2 to 2.2 log units for total coliforms (TC) and from 1.4 to 2.3 log units for E. coli. The presence of fine granulometry strongly influenced the removal of all the bacterial groups analyzed. This effect was significant for TC (p=0.009), E. coli (p=0.004), and FE (p=0.012). Shallow HSSF constructed wetlands were more effective for removing Clostridium spores (p=0.039), and were also more efficient for removing TC (p=0.011) and E. coli (p=0.013) when fine granulometry was used. On the other hand, changes in the total bacterial community from gravel biofilm were examined by using denaturing gradient gel electrophoresis (DGGE) and sequencing of polymerase chain reaction (PCR)-amplified fragments of the 16S rRNA gene recovered from DGGE bands. Cluster analysis of the DGGE banding pattern from the different wetlands showed that microbial assemblages separated according to water depth, and sequences of different phylogenetic groups, such as Alpha, Beta and Delta-Proteobacteria, Nitrospirae, Bacteroidetes

  17. Anabolic-androgenic steroid use among Brazilian bodybuilders.

    PubMed

    Nogueira, Fabiana Ranielle de Siqueira; Brito, Aline de Freitas; Oliveira, Caio Victor Coutinho de; Vieira, Thaiza Isidro; Gouveia, Rachel Linka Beniz

    2014-07-01

    This cross-sectional, quantitative, exploratory study investigated the prevalence and profile of anabolic-androgenic steroids (AAS) users amongst a convenience sample of 510 bodybuilders from 52 gyms, in João Pessoa, Brazil, with a structured questionnaire containing selected questions about socioeconomic and training variables on the use of AAS. Data were analyzed using frequency and chi-square tests. AAS prevalence use was 20.6%; mostly young men (98.1%), of a low education level (46.7%), who trained for more than 4 years (49.5%). The use of AAS was related to the use of dietary supplements. About 81% of consumed AAS consisted of Deca-Durabolin, Winstrol, and Sustanon. Study's limitations are noted.

  18. National Athletic Trainers' Association Position Statement: Anabolic-Androgenic Steroids

    PubMed Central

    Kersey, Robert D.; Elliot, Diane L.; Goldberg, Linn; Kanayama, Gen; Leone, James E.; Pavlovich, Mike; Pope, Harrison G.

    2012-01-01

    This NATA position statement was developed by the NATA Research & Education Foundation. Objective This manuscript summarizes the best available scholarly evidence related to anabolic-androgenic steroids (AAS) as a reference for health care professionals, including athletic trainers, educators, and interested others. Background Health care professionals associated with sports or exercise should understand and be prepared to educate others about AAS. These synthetic, testosterone-based derivatives are widely abused by athletes and nonathletes to gain athletic performance advantages, develop their physiques, and improve their body image. Although AAS can be ergogenic, their abuse may lead to numerous negative health effects. Recommendations Abusers of AAS often rely on questionable information sources. Sports medicine professionals can therefore serve an important role by providing accurate, reliable information. The recommendations provide health care professionals with a current and accurate synopsis of the AAS-related research. PMID:23068595

  19. Anabolic steroid abuse and dependence in clinical practice.

    PubMed

    Brower, Kirk J

    2009-12-01

    The nonmedical use of anabolic-androgenic steroids (AAS) appeals to athletes across several sports, particularly those whose activity makes muscle size and strength advantageous, and in individuals (usually men) with body dysmorphic disorder. Patterns of nonmedical use, including supratherapeutic doses of illicitly obtained drugs, increase the risk for adverse psychiatric and other medical consequences. Although AAS users may be more likely to consult physicians for nonpsychiatric medical consequences than changes in their mental status, it is argued that the motivation for persistent use despite adverse consequences is sustained in large part by psychological variables. Therefore, all physicians who treat nonmedical AAS users will benefit from an understanding of these psychological variables, including the potential for AAS to cause dependence. This article aims to aid such understanding, and guidelines are suggested for assessment and treatment of nonmedical AAS users.

  20. When color fails: illicit blue tablets containing anabolic androgen steroids.

    PubMed

    Favretto, Donata; Castagna, Franca; Maietti, Sergio; Boscolo-Berto, Rafael; Ferrara, Santo Davide

    2013-09-01

    The necessity of specific, confirmatory tests in the identification of seized illicit products was highlighted by the analysis of eighteen heart shaped, blue tablets confiscated by Police at a street control in the North East of Italy. The tablets responded as amphetamines to a preliminary color test (Marquis); a subsequent, confirmatory assay by gas chromatography-mass spectrometry revealed the presence of two anabolic androgen steroids (AAS), methandienone and methyltestosterone, in concentration of 1.7 and 1.5mg respectively per tablet; no trace of amphetamine-like or nitrogen containing compounds was found. The observed orange coloration was due to the reaction of concentrated sulphuric acid, contained in the Marquis reagent, with the Δ(4) C-3 keto group of steroids. The two AAS, banned under the world antidoping code, are not considered as psychoactive drugs of abuse in most countries, although their trafficking may entangle severe public health concerns.

  1. Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid.

    PubMed

    Ambrus, C M; Ambrus, J L

    1975-01-01

    Stumptail monkeys (Macaca speciosa) received lethal whole body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colonyforming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls.

  2. Anabolic Steroid Abuse among Teenage Girls: An Illusory Problem?

    PubMed Central

    Kanayama, Gen; Boynes, Matthew; Hudson, James I.; Field, Alison E.; Pope, Harrison G.

    2007-01-01

    Background Recent media reports have portrayed an alarming increase in apparent anabolic-androgenic steroid (AAS) use among American teenage girls; Congress even held hearings on the subject in June 2005. We questioned whether AAS use among teenage girls was as widespread as claimed. Methods We reviewed four large national surveys and many smaller surveys examining the prevalence of AAS use among teenage girls. Virtually all of these surveys used anonymous questionnaires. We asked particularly whether the language of survey questions might generate false-positive responses among girls who misinterpreted the term “steroid.” We also reviewed data from other countries, together with results from the only recent study (to our knowledge) in which investigators personally interviewed female AAS users. Results The surveys produced remarkably disparate findings, with the lifetime prevalence of AAS use estimated as high as 7.3% among ninth-grade girls in one study, but only 0.1% among teenage girls in several others. Upon examining the surveys reporting an elevated prevalence, it appeared that most used questions that failed to distinguish between anabolic steroids, corticosteroids, and over-the-counter supplements that respondents might confuse with “steroids.” Other features in the phrasing of certain questions also seemed likely to further bias results in favor of false-positive responses. Conclusions Many anonymous surveys, using imprecise questions, appear to have greatly overestimated the lifetime prevalence of AAS use among teenage girls; the true lifetime prevalence may well be as low as 0.1%. Future studies can test this impression by using a carefully phrased question regarding AAS use. PMID:17127018

  3. Hepatic neoplasms associated with contraceptive and anabolic steroids.

    PubMed

    Ishak, K G

    1979-01-01

    This paper evaluates the differences between HCA (hepatocellular adenoma) and FNH (focal nodular hyperplasia) and the association of HCA and FNH with OC (oral contraceptives). FNH occurs at least twice as frequent in females as in males. A study conducted by the author revealed that only 20% of patients with FNH had symptoms and signs related to their neoplasms; in the rest, FNH was accidentally discovered during surgery for diseases of the gallbladder or at necropsy. The highly characteristic gross appearance of FNH is discribed in detail. The etiologic relationship between FNH and OC was cited in the light of frequent findings of FNH in infants and children, and of suggestions by other authors that FNH could be a direct result on OC therapy or that contraceptive steroids or conjugated estrogens accelerate the growth of FNH, a very slow growing neoplasm. Simple excision is the treatment of choice for FNH; in some cases, hepatic artery ligation is indicated. In the case of HCA, statistics show that the incidence of HCA has been increasing since 1960. Majority of patients with HCA have normal tests of hepatic function. Radiographic studies and hepatic scans may reveal HCA, but the best diagnostic method so far is angiography. Although gross appearance of HCA is variable, the features are clearly distinguishable from that of FNH. Other topics discussed include the occasional occurence of nodular regenerative hyperplasia in patients on OC or anabolic steroids (AS), and malignant liver tumors in patients using OC or AS. Further research should be done to clarify the etiologic relationship between androgenic-anabolic steroids and hepatocellular tumors and tumorlike lesions.

  4. Preparation and application of solid-phase microextraction fiber based on molecularly imprinted polymer for determination of anabolic steroids in complicated samples.

    PubMed

    Qiu, Lijun; Liu, Wei; Huang, Min; Zhang, Lan

    2010-11-26

    A relatively selective, chemically and physically robust SPME fiber was developed in a simple way with testosterone-imprinted polymer, and then directly coupled with gas chromatography-mass spectrometry (GC-MS) for selective extraction and analysis of anabolic steroids. The factors influencing polymerization (i.e., cross-linker, polymerization solvent, polymerization time) were optimized in detail and the polymer was characterized by scanning electron microscope, infrared spectrometer and thermogravimetric analyzer. Furthermore, the extraction performance of the MIP-coated SPME fibers such as extraction ability and selectivity was evaluated. Moreover, the interaction mode between target analytes and fiber coating was deducted. Finally, the method for extraction and determination of androsterone, stanolone, androstenedione and methyltestosterone by the homemade MIP-coated SPME fibers with GC-MS was obtained. It was applied to the simultaneous analysis of four anabolic steroids in the spiked human urine with the satisfactory recoveries.

  5. An analysis of key stakeholders' attitudes and beliefs about barriers and facilitating factors in the development of a cervical cancer prevention program in South Africa.

    PubMed

    Francis, Shelley A; Leser, Kendall A; Esmont, Emma E; Griffith, Fareeda M

    2013-03-01

    Cervical cancer is the leading cause of cancer related deaths among women. Each year there are approximately 250,000 deaths; most of which occurred in Sub-Saharan Africa, South Asia, and Latin America. The purpose of this report is to examine key stakeholders experience and knowledge of HPV and cervical cancer, examine their experiences with the current cervical cancer screening and treatment policy, and identify barriers and facilitating factors to vaccine implementation and uptake. Fifteen indepth interviews were conducted with key stakeholders in Cape Town and Johannesburg, South Africa. The interviews revealed several key findings including: 1) knowledge about HPV and cervical cancer varied across participants, 2) knowledge about cervical cancer was also mixed while knowledge about the relationship between HPV and cervical cancer was low among participants. Our findings indicate that key stakeholders are concerned about women's health and wellbeing. In addition, they believe that the government, families, and the media need to play a prominent role in prevention efforts.

  6. Student-University Relationships and Reputation: A Study of the Links between Key Factors Fostering Students' Supportive Behavioral Intentions towards Their University

    ERIC Educational Resources Information Center

    Sung, Minjung; Yang, Sung-Un

    2009-01-01

    Focusing on academic institutions in higher education as the research context, this study examined the relations of key factors affecting students' supportive behavioral intentions toward the university (e.g., giving gifts as alumni, continuing education, and giving referrals regarding the university). Based on the literature from various…

  7. Periods of child growth up to age 8 years in Ethiopia, India, Peru and Vietnam: key distal household and community factors.

    PubMed

    Schott, Whitney B; Crookston, Benjamin T; Lundeen, Elizabeth A; Stein, Aryeh D; Behrman, Jere R

    2013-11-01

    Recent research has demonstrated some growth recovery among children stunted in infancy. Less is known about key age ranges for such growth recovery, and what factors are correlates with this growth. This study characterized child growth up to age 1 year, and from ages 1 to 5 and 5 to 8 years controlling for initial height-for-age z-score (HAZ), and identified key distal household and community factors associated with these growth measures using longitudinal data on 7266 children in the Young Lives (YL) study in Ethiopia, India, Peru and Vietnam. HAZ at about age 1 year and age in months predicted much of the variation in HAZ at age 5 years, but 40-71% was not predicted. Similarly, HAZ at age 5 years and age in months did not predict 26-47% of variation in HAZ at 8 years. Multiple regression analysis suggests that parental schooling, consumption, and mothers' height are key correlates of HAZ at about age 1 and also are associated with unpredicted change in HAZ from ages 1 to 5 and 5 to 8 years, given initial HAZ. These results underline the importance of a child's starting point in infancy in determining his or her growth, point to key distal household and community factors that may determine early growth in early life and subsequent growth recovery and growth failure, and indicate that these factors vary some by country, urban/rural designation, and child sex.

  8. A Study of the Relationship between Key Factors of Academic Innovation and Faculties' Teaching Goals--The Mediatory Role of Knowledge

    ERIC Educational Resources Information Center

    Mohammadi, Mehdi; Marzooghi, Rahmatullah; Dehghani, Fatemeh

    2017-01-01

    The following research tries to study the Relationship between key factors of academic innovations and faculties' teaching goals with the mediatory role of their pedagogical, technological and content knowledge. The statistical population in this research included faculty members of Shiraz University. By simple random sampling, 127 faculty members…

  9. Dynamic C and N stocks - key factors controlling the C gas exchange of maize in heterogenous peatland

    NASA Astrophysics Data System (ADS)

    Pohl, M.; Hoffmann, M.; Hagemann, U.; Giebels, M.; Albiac Borraz, E.; Sommer, M.; Augustin, J.

    2015-05-01

    The drainage and cultivation of fen peatlands create complex small-scale mosaics of soils with extremely variable soil organic carbon (SOC) stocks and groundwater levels (GWLs). To date, the significance of such sites as sources or sinks for greenhouse gases such as CO2 and CH4 is still unclear, especially if the sites are used for cropland. As individual control factors such as GWL fail to account for this complexity, holistic approaches combining gas fluxes with the underlying processes are required to understand the carbon (C) gas exchange of drained fens. It can be assumed that the stocks of SOC and N located above the variable GWL - defined as dynamic C and N stocks - play a key role in the regulation of the plant- and microbially mediated CO2 fluxes in these soils and, inversely, for CH4. To test this assumption, the present study analysed the C gas exchange (gross primary production - GPP; ecosystem respiration - Reco; net ecosystem exchange - NEE; CH4) of maize using manual chambers for 4 years. The study sites were located near Paulinenaue, Germany, where we selected three soil types representing the full gradient of GWL and SOC stocks (0-1 m) of the landscape: (a) Haplic Arenosol (AR; 8 kg C m-2); (b) Mollic Gleysol (GL; 38 kg C m-2); and (c) Hemic Histosol (HS; 87 kg C m-2). Daily GWL data were used to calculate dynamic SOC (SOCdyn) and N (Ndyn) stocks. Average annual NEE differed considerably among sites, ranging from 47 ± 30 g C m-2 yr-1 in AR to -305 ± 123 g C m-2 yr-1 in GL and -127 ± 212 g C m-2 yr-1 in HS. While static SOC and N stocks showed no significant effect on C fluxes, SOCdyn and Ndyn and their interaction with GWL strongly influenced the C gas exchange, particularly NEE and the GPP : Reco ratio. Moreover, based on nonlinear regression analysis, 86% of NEE variability was explained by GWL and SOCdyn. The observed high relevance of dynamic SOC and N stocks in the aerobic zone for plant and soil gas exchange likely originates from the

  10. Dynamic C and N stocks - key factors controlling the C gas exchange of maize in a heterogenous peatland

    NASA Astrophysics Data System (ADS)

    Pohl, M.; Hoffmann, M.; Hagemann, U.; Giebels, M.; Albiac Borraz, E.; Sommer, M.; Augustin, J.

    2014-11-01

    Drainage and cultivation of fen peatlands creates complex small-scale mosaics of soils with extremely variable soil organic carbon (SOC) stocks and groundwater-level (GWL). To date, it remains unclear if such sites are sources or sinks for greenhouse gases like CO2 and CH4, especially if used for cropland. As individual control factors like GWL fail to account for this complexity, holistic approaches combining gas fluxes with the underlying processes are required to understand the carbon (C) gas exchange of drained fens. It can be assumed that the stocks of SOC and N located above the variable GWL - defined as dynamic C and N stocks - play a key role in the regulation of plant- and microbially mediated C gas fluxes of these soils. To test this assumption, the present study analysed the C gas exchange (gross primary production - GPP, ecosystem respiration - Reco, net ecosystem exchange - NEE, CH4) of maize using manual chambers for four years. The study sites were located near Paulinenaue, Germany. Here we selected three soils, which represent the full gradient in pedogenesis, GWL and SOC stocks (0-1 m) of the fen peatland: (a) Haplic Arenosol (AR; 8 kg C m-2); (b) Mollic Gleysol (GL; 38 kg C m-2); and (c) Hemic Histosol (HS; 87 kg C m-2). Daily GWL data was used to calculate dynamic SOC (SOCdyn) and N (Ndyn) stocks. Average annual NEE differed considerably among sites, ranging from 47 ± 30 g C m-2 a-1 at AR to -305 ± 123 g C m-2 a-1 at GL and -127 ± 212 g C m-2 a-1 at HS. While static SOC and N stocks showed no significant effect on C fluxes, SOCdyn and Ndyn and their interaction with GWL strongly influenced the C gas exchange, particularly NEE and the GPP:Reco ratio. Moreover, based on nonlinear regression analysis, 86% of NEE variability was explained by GWL and SOCdyn. The observed high relevance of dynamic SOC and N stocks in the aerobic zone for plant and soil gas exchange likely originates from the effects of GWL-dependent N availability on C formation and

  11. The Evaluation of Vehicle Mass Reduction and Material Choice in Life Cycle Assessments: Key Factors and Dynamic Industries

    EPA Science Inventory

    Developments in the realm of lightweight materials for automotive use continue to be announced by the industry and by academia. This session will provide new and updated information on new generation of materials. Additionally, this session will focus on the key topics involved i...

  12. The key factor limiting plant growth in cold and humid alpine areas also plays a dominant role in plant carbon isotope discrimination.

    PubMed

    Xu, Meng; Wang, Guoan; Li, Xiaoliang; Cai, Xiaobu; Li, Xiaolin; Christie, Peter; Zhang, Junling

    2015-01-01

    Many environmental factors affect carbon isotope discrimination in plants, yet the predominant factor influencing this process is generally assumed to be the key growth-limiting factor. However, to our knowledge this hypothesis has not been confirmed. We therefore determined the carbon isotope composition (δ(13)C) of plants growing in two cold and humid mountain regions where temperature is considered to be the key growth-limiting factor. Mean annual temperature (MAT) showed a significant impact on variation in carbon isotope discrimination value (Δ) irrespective of study area or plant functional type with either partial correlation or regression analysis, but the correlation between Δ and soil water content (SWC) was usually not significant. In multiple stepwise regression analysis, MAT was either the first or the only variable selected into the prediction model of Δ against MAT and SWC, indicating that the effect of temperature on carbon isotope discrimination was predominant. The results therefore provide evidence that the key growth-limiting factor is also crucial for plant carbon isotope discrimination. Changes in leaf morphology, water viscosity and carboxylation efficiency with temperature may be responsible for the observed positive correlation between Δ and temperature.

  13. Decreased Levels of Proapoptotic Factors and Increased Key Regulators of Mitochondrial Biogenesis Constitute New Potential Beneficial Features of Long-lived Growth Hormone Receptor Gene–Disrupted Mice

    PubMed Central

    2013-01-01

    Decreased somatotrophic signaling is among the most important mechanisms associated with extended longevity. Mice homozygous for the targeted disruption of the growth hormone (GH) receptor gene (GH receptor knockout; GHRKO) are obese and dwarf, are characterized by a reduced weight and body size, undetectable levels of GH receptor, high concentration of serum GH, and greatly reduced plasma levels of insulin and insulin-like growth factor-I, and are remarkably long lived. Recent results suggest new features of GHRKO mice that may positively affect longevity—decreased levels of proapoptotic factors and increased levels of key regulators of mitochondrial biogenesis. The alterations in levels of the proapoptotic factors and key regulators of mitochondrial biogenesis were not further improved by two other potential life-extending interventions—calorie restriction and visceral fat removal. This may attribute the primary role to GH resistance in the regulation of apoptosis and mitochondrial biogenesis in GHRKO mice in terms of increased life span. PMID:23197187

  14. Use of anabolic-androgenic steroids among body builders--frequency and attitudes.

    PubMed

    Lindström, M; Nilsson, A L; Katzman, P L; Janzon, L; Dymling, J F

    1990-06-01

    A total of 138 male body builders who regularly attended a gym participated anonymously in a study of the use of anabolic-androgenic steroids in relation to side-effects, blood pressure, body mass index (BMI; kg m-2), training frequency, social background, occupation, knowledge and attitudes to steroid use. Fifty-three of the 138 body builders had used anabolic-androgenic steroids for a median duration of 2 years. Steroid use was linked to a higher BMI and more frequent training. Seventy-five per cent (n = 18) of those attending body building for competition, and 24% (n = 11) of those attending to improve their sense of well-being, used anabolic-androgenic steroids. Of all body builders, 94% considered anabolic-androgenic steroids to be dangerous. Of the users, 81% experienced side-effects, but 74% still intended to continue steroid medication.

  15. Altered Serum Lipoprotein Profiles in Male and Female Power Lifters Ingesting Anabolic Steroids.

    ERIC Educational Resources Information Center

    Cohen, Jonathan C.; And Others

    1986-01-01

    Serum lipoprotein profiles were measured in nine male and three female weightlifters who were taking anabolic steroids. The profiles suggest that steriod users may face an increased risk of coronary artery disease. (Author/MT)

  16. Acute hereditary coproporphyria induced by the androgenic/anabolic steroid methandrostenolone (Dianabol).

    PubMed

    Lane, P R; Massey, K L; Worobetz, L J; Jutras, M N; Hull, P R

    1994-02-01

    Acute attacks of porphyria can be induced by certain drugs. We report a case of acute coproporphyria induced by methandrostenolone. This is the first report of acute porphyria induced by an androgenic, anabolic steroid.

  17. Anabolic Steroids: Metabolism, Doping and Detection in Human and Equestrian Sports

    NASA Astrophysics Data System (ADS)

    Kicman, A. T.; Houghton, E.; Gower, D. B.

    This chapter highlights the important aspects of detection of doping with synthetic anabolic steroids and discusses some of the problems with, and solutions to, the detection of misuse of the naturally occurring ones.

  18. The Use and Abuse of Anabolic Steroids: A Discussion for Health and Physical Education Teachers

    ERIC Educational Resources Information Center

    Thomas, John A.; And Others

    1973-01-01

    This article reviews research on anabolic steroids, indicating that athletes are mistaken in believing that taking them will improve their physical performance. Dangerous side-effects are also discussed. (JA)

  19. [Effect of an anabolic steroid on the cellular immunity and postoperative evaluation of uterine cervical cancer].

    PubMed

    Ooshika, Y; Umesaki, N; Sako, H; Kawabata, M; Sugana, T

    1984-10-01

    The effects of an anabolic steroid on the immune activity and clinical condition of patients with cancer of the uterine cervix were studied. The effects of the steroid on tumor growth were also studied in animals. The results obtained demonstrated that the anabolic steroid (1) enhanced the activity of macrophages and cell-mediated immune activity, (2) reduced the incidence of post-operative infection, (3) reduced pose-operative loss of weight of patients due to the intrinsic anabolic activity of the steroid, and (4) did not exert any influence on tumor growth. Judging from these results, administration of the anabolic steroid would appear to be effective for the improvement of the general condition of cancer patients following surgery or in terminal cases.

  20. Compulsive weight lifting and anabolic drug abuse among women rape victims.

    PubMed

    Gruber, A J; Pope, H G

    1999-01-01

    In the course of a study of 75 female weight lifters, we encountered 10 (13%) who reported that they were raped as teenagers or adults. Nine of these women began or greatly increased their weight lifting activities after the assault to be better able to defend themselves against men. Seven began abusing anabolic steroids and/or clenbuterol to gain muscle mass. Compulsive weight lifting and anabolic substance abuse may represent another form of response to the trauma of sexual assault.

  1. Prevalence of Use of Anabolic Steroids by Bodybuilders Using Three Methods in a City of Iran

    PubMed Central

    Nakhaee, Mohammad Reza; Pakravan, Faezeh; Nakhaee, Nouzar

    2013-01-01

    Background The prevalence of substance use among bodybuilding athletes has been poorly studied in Iran. This study was conducted to examine the prevalence of drug use, especially anabolic steroids, among bodybuilding athletes. Methods This cross-sectional study was conducted in the first half of 2013 among body building athletes referring to gyms located in Kerman, Iran. Five gyms were selected randomly and 380 athletes were invited to complete a self-administered anonymous questionnaire, consecutively. The questionnaire included two parts; baseline characteristics and substance related questions. The prevalence of anabolic steroids was estimated based on three methods; self-report, projective question, and crosswise model. Findings We enrolled 298 male athletes in the final analysis. Mean ± SD age of subjects was 25.9 ± 8.4. The most frequent recent (past 30 days) drug use was waterpipe smoking (45%). The second most frequently used drug was alcohol (26.5%, recent use). Based on self-reports, the prevalence of lifetime anabolic steroid use was calculated to be 24.5%. The corresponding figure based on crosswise method was obtained to be 56.8%. Participants believed that a median of 40% of athletes had used anabolic steroids in their lifetime. The prevalence of anabolic steroid was higher in single and less educated individuals (P < 0.05). The main reason for using anabolic steroids was to increase muscle size. Conclusion The prevalence of drug use, especially tobacco, alcohol, and anabolic steroids, was high among bodybuilding athletes. We could not rely on self-reports to examine anabolic steroid use. PMID:24494162

  2. Cardiotoxic effects of cocaine and anabolic-androgenic steroids in the athlete.

    PubMed

    Welder, A A; Melchert, R B

    1993-04-01

    Cocaine and anabolic-androgenic steroid abuse have become major drug problems in the United States. Cocaine has been designated as "the drug of greatest national health concern" while as many as 1 million Americans have used or are currently using anabolic-androgenic steroids to promote athletic performance and/or improve physical appearance. Unfavorable cardiovascular events have been linked to both cocaine and anabolic-androgenic steroid abuse in healthy, physically active individuals. Deaths of several United States athletes in 1986 focused attention on the life-threatening cardiovascular consequences of cocaine abuse. Reports of myocardial injury with anabolic-androgenic steroid abuse are anecdotal. Nevertheless, case reports have illustrated the alarming cardiotoxic potential of these steroids in athletes. Anabolic-androgenic steroids were correlated to myocardial infarction in weight lifters and cardiomyopathy in a former professional football player. From the total emergency room episodes where cocaine was mentioned in 1990, approximately 66% of these episodes occurred in young individuals 18-29 years of age. Over 500,000 of the individuals currently taking anabolic-androgenic steroids for nonmedical purposes are high-school children. Because cocaine and anabolic-androgenic steroids are used improperly, more focus needs to be paid to the toxic mechanisms of their adverse effects. Therefore, the purpose of this review is to discuss mechanisms whereby exercise and/or exercise training may alter the cardiovascular responses to these drugs. Furthermore, we would like to illustrate that contrary to the popular belief, acute and chronic abuse of cocaine and anabolic-androgenic steroids have a negative impact on exercise performance.

  3. Men regret anabolic steroid use due to a lack of comprehension regarding the consequences on future fertility.

    PubMed

    Kovac, J R; Scovell, J; Ramasamy, R; Rajanahally, S; Coward, R M; Smith, R P; Lipshultz, L I

    2015-10-01

    We examined whether men with anabolic-steroid-induced hypogonadism (ASIH) seeking testosterone supplementation therapy (TST) regretted their decision to use anabolic-androgenic steroids (AAS) and what their reasons were for this regret. An anonymous, prospective survey was distributed to 382 men seeking follow-up treatment for hypogonadism. Prior AAS use was confirmed by self-report, and men were categorised based upon whether they regretted (R) or did not regret (NR) their use of AAS. The average patient age was 40 ± 0.9 years (n = 79) and 15.2% expressed regret over AAS use. No demographic differences were identified between those who regretted AAS use (n = 12) and those who did not (n = 67). Regret was not related to ASIH diagnosis or to AAS-related side effects like increased aggression, mood disorders, erectile dysfunction, acne, fluid retention or dyslipidemia. Those who regretted AAS use were significantly more likely to have not comprehended the negative impact on future fertility (P < 0.030). Actual fertility issues were comparable in men who regretted AAS use (16.7%) and those who did not (13%). A total of 15.2% of men regretted using AAS. A lack of awareness regarding the negative long-term effects on fertility was the primary factor related to regret of AAS use in men with ASIH.

  4. Role of paraoxonase-1 in bone anabolic effects of parathyroid hormone in hyperlipidemic mice

    SciTech Connect

    Lu, Jinxiu; Cheng, Henry; Atti, Elisa; Shih, Diana M.; Demer, Linda L.; Tintut, Yin

    2013-02-01

    Highlights: ► Anabolic effects of PTH were tested in hyperlipidemic mice overexpressing PON1. ► Expression of antioxidant regulatory genes was induced in PON1 overexpression. ► Bone resorptive activity was reduced in PON1 overexpressing hyperlipidemic mice. ► PON1 restored responsiveness to intermittent PTH in bones of hyperlipidemic mice. -- Abstract: Hyperlipidemia blunts anabolic effects of intermittent parathyroid hormone (PTH) on cortical bone, and the responsiveness to PTH are restored in part by oral administration of the antioxidant ApoA-I mimetic peptide, D-4F. To evaluate the mechanism of this rescue, hyperlipidemic mice overexpressing the high-density lipoprotein-associated antioxidant enzyme, paraoxonase 1 (Ldlr{sup −/−}PON1{sup tg}) were generated, and daily PTH injections were administered to Ldlr{sup −/−}PON1{sup tg} and to littermate Ldlr{sup −/−} mice. Expression of bone regulatory genes was determined by realtime RT-qPCR, and cortical bone parameters of the femoral bones by micro-computed tomographic analyses. PTH-treated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTH receptor (PTH1R), activating transcription factor-4 (ATF4), and osteoprotegerin (OPG) in femoral cortical bone, as well as significantly greater cortical bone mineral content, thickness, and area in femoral diaphyses compared with untreated Ldlr{sup −/−}PON1{sup tg} mice. In contrast, in control mice (Ldlr{sup −/−}) without PON1 overexpression, PTH treatment did not induce these markers. Calvarial bone of PTH-treated Ldlr{sup −/−}PON1{sup tg} mice also had significantly greater expression of osteoblastic differentiation marker genes as well as BMP-2-target and Wnt-target genes. Untreated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTHR1 than untreated Ldlr{sup −/−} mice, whereas sclerostin expression was reduced. In femoral cortical bones, expression levels of transcription factors, Fox

  5. Dasatinib as a Bone-Modifying Agent: Anabolic and Anti-Resorptive Effects

    PubMed Central

    Garcia-Gomez, Antonio; Ocio, Enrique M.; Crusoe, Edvan; Santamaria, Carlos; Hernández-Campo, Pilar; Blanco, Juan F.; Sanchez-Guijo, Fermin M.; Hernández-Iglesias, Teresa; Briñón, Jesús G.; Fisac-Herrero, Rosa M.; Lee, Francis Y.; Pandiella, Atanasio; San Miguel, Jesús F.; Garayoa, Mercedes

    2012-01-01

    Background Bone loss, in malignant or non-malignant diseases, is caused by increased osteoclast resorption and/or reduced osteoblast bone formation, and is commonly associated with skeletal complications. Thus, there is a need to identify new agents capable of influencing bone remodeling. We aimed to further pre-clinically evaluate the effects of dasatinib (BMS-354825), a multitargeted tyrosine kinase inhibitor, on osteoblast and osteoclast differentiation and function. Methods For studies on osteoblasts, primary human bone marrow mensenchymal stem cells (hMSCs) together with the hMSC-TERT and the MG-63 cell lines were employed. Osteoclasts were generated from peripheral blood mononuclear cells (PBMC) of healthy volunteers. Skeletally-immature CD1 mice were used in the in vivo model. Results Dasatinib inhibited the platelet derived growth factor receptor-β (PDGFR-β), c-Src and c-Kit phosphorylation in hMSC-TERT and MG-63 cell lines, which was associated with decreased cell proliferation and activation of canonical Wnt signaling. Treatment of MSCs from healthy donors, but also from multiple myeloma patients with low doses of dasatinib (2–5 nM), promoted its osteogenic differentiation and matrix mineralization. The bone anabolic effect of dasatinib was also observed in vivo by targeting endogenous osteoprogenitors, as assessed by elevated serum levels of bone formation markers, and increased trabecular microarchitecture and number of osteoblast-like cells. By in vitro exposure of hemopoietic progenitors to a similar range of dasatinib concentrations (1–2 nM), novel biological sequelae relative to inhibition of osteoclast formation and resorptive function were identified, including F-actin ring disruption, reduced levels of c-Fos and of nuclear factor of activated T cells 1 (NFATc1) in the nucleus, together with lowered cathepsin K, αVβ3 integrin and CCR1 expression. Conclusions Low dasatinib concentrations show convergent bone anabolic and reduced bone

  6. Growth and anabolic hormones, leptin, and neuromuscular performance in moderately trained prepubescent athletes and untrained boys.

    PubMed

    Tsolakis, Charilaos; Vagenas, George; Dessypris, Athanasios

    2003-02-01

    We investigated hormonal regulators of growth and development, leptin levels, body composition, neuromuscular performance, and the associations among them in trained prepubertal athletes (experimental group [EG]) and an untrained control group (CG). Informed consent was obtained from the children and their parents. Their maturation stage was evaluated according to Tanner's criteria. There were no differences between EG and CG in physical characteristics, body mass index (BMI), lean body mass, testosterone (T), sex hormone-binding globulin, free androgen index, growth hormone (GH), hand grip strength, and jumping performance. Leptin levels and percent fat of the EG were significantly lower than those of the CG (p < 0.05-0.005). Leptin levels were significantly correlated to body fat and BMI for both the EG and the CG (r = 0.51-0.79). There is little evidence that leptin has a positive effect on growth and anabolic factors. Sex hormone-binding globulin and GH may explain the variation of leptin in athletes with low T (R(2) = 0.43) and in CG (R(2) = 0.35), respectively. Leptin seems to be a permissive factor for the onset of puberty, and the training background needs an optimal biological maturation to produce significant differences in muscle and power performance.

  7. Insulin is protein-anabolic in chronic renal failure patients.

    PubMed

    Lim, Victoria S; Yarasheski, Kevin E; Crowley, Jan R; Fangman, Jerry; Flanigan, Michael

    2003-09-01

    To examine the protein anabolic actions of insulin in chronic renal failure, the authors measured four sets of whole body leucine fluxes during insulin alone and insulin with amino acid infusion in nine uremic patients before hemodialysis (B-HD). Seven were restudied 8 wk after initiation of maintenance hemodialysis (HD). Six normal subjects served as control (N). All values ( micro mol/kg/h, mean +/- SEM) are presented in the sequence of B-HD, HD, and N, and only P < 0.05 are listed. During Flux 1 (baseline), D (leucine release from body protein degradation) were 114 +/- 7, 126 +/- 4, and 116 +/- 6, respectively. C (leucine oxidation rates) were 18 +/- 2, 17 +/- 2, and 21 +/- 3, respectively. S (leucine disappearance into body protein [index of protein synthesis]) were 96 +/- 6, 107 +/- 4, and 94 +/- 4, respectively, and balances (net leucine flux into protein [values were negative during fasting]) were -18 +/- 2, -17 +/- 2, and -21 +/- 3, respectively. During Flux 2 (low-dose insulin infusion), D were 89 +/- 3, 98 +/- 6, and 94 +/- 5, respectively; C were 12 +/- 1, 11 +/- 2, and 18 +/- 1, respectively (P = 0.02); S were 77 +/- 4, 87 +/- 5, and 76 +/- 5, respectively, and balances were -12 +/- 1, -11 +/- 2, and -18 +/- 1, respectively (P = 0.02). During Flux 3 (high-dose insulin infusion): D were 77 +/- 3, 82 +/- 7, and 84 +/- 5, respectively; C were 9 +/- 1, 8 +/- 1, and 14 +/- 1, respectively (P = 0.005); S were 68 +/- 4, 74 +/- 6, and 70 +/- 5, respectively, and balances were -9 +/- 1, -8 +/- 1, and -14 +/- 1, respectively (P = 0.005). In Flux 4 (insulin infused with amino acids): D were 73 +/- 3, 107 +/- 18, and 85 +/- 7, respectively; C were 35 +/- 4, 29 +/- 5, and 39 +/- 3, respectively; S were 105 +/- 5, 145 +/- 15, and 113 +/- 6, respectively (P = 0.02), and balances were 32 +/- 4, 38 +/- 5, and 27 +/- 3, respectively. These data show that B-HD and HD patients were as sensitive as normal subjects to the protein anabolic actions of insulin. Insulin alone

  8. siRNA and shRNA screens advance key understanding of host factors required for HIV-1 replication.

    PubMed

    Kok, Kin-Hang; Lei, Ting; Jin, Dong-Yan

    2009-08-27

    A recent RNAi screen used a genome-wide shRNA library to search for cellular factors required for HIV-1 replication. This work complements three other siRNA-based screening studies and potentially opens the door to the discovery of factors that are important for HIV-1 replication in physiological host cells such as T lymphocytes. shRNA screens can be further improved, and they could promise to unravel new pathways and new facets of virus-cell interactions.

  9. Analysis of transcription factors key for mouse pancreatic development establishes NKX2-2 and MNX1 mutations as causes of neonatal diabetes in man.

    PubMed

    Flanagan, Sarah E; De Franco, Elisa; Lango Allen, Hana; Zerah, Michele; Abdul-Rasoul, Majedah M; Edge, Julie A; Stewart, Helen; Alamiri, Elham; Hussain, Khalid; Wallis, Sam; de Vries, Liat; Rubio-Cabezas, Oscar; Houghton, Jayne A L; Edghill, Emma L; Patch, Ann-Marie; Ellard, Sian; Hattersley, Andrew T

    2014-01-07

    Understanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge of key transcriptional regulators has predominantly come from mouse studies, with rare, naturally occurring mutations establishing their relevance in man. This study used a combination of homozygosity analysis and Sanger sequencing in 37 consanguineous patients with permanent neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development. We identified homozygous mutations in 7 different genes in 11 unrelated patients and show that NKX2-2 and MNX1 are etiological genes for neonatal diabetes, thus confirming their key role in development of the human pancreas. The similar phenotype of the patients with recessive mutations and mice with inactivation of a transcription factor gene support there being common steps critical for pancreatic development and validate the use of rodent models for beta cell development.

  10. Independent Control of Organogenesis and Shoot Tip Abortion are Key Factors to Developmental Plasticity in Kiwifruit (Actinidia)

    PubMed Central

    Foster, Toshi M.; Seleznyova, Alla N.; Barnett, Andrew M.

    2007-01-01

    Background and Aims In kiwifruit (Actinidia), the number of nodes per shoot is highly variable and is influenced by genotype and environmental conditions. To understand this developmental plasticity, three key processes were studied: organogenesis by the shoot apical meristem during shoot growth; expansion of phytomers; and shoot tip abortion. Methods Studies were made of organogenesis and shoot tip abortion using light and scanning electron microscopy. The effect of temperature on shoot growth cessation was investigated using temperature indices over the budbreak period, and patterns of shoot tip abortion were quantified using stochastic modelling. Key Results All growing buds began organogenesis before budbreak. During shoot development, the number of phytomers initiated by the shoot apical meristem is correlated with the number of expanding phytomers and the mean internode length. Shoot tip abortion is preceded by growth cessation and is not brought about by the death of the shoot apical meristem, but occurs by tissue necrosis in the sub-apical zone. For most genotypes studied, the probability of shoot tip abortion is higher during expansion of the preformed part of the shoot. Lower temperatures during early growth result in a higher probability of shoot tip abortion. Conclusions Organogenesis and shoot tip abortion are controlled independently. All buds have the potential to become long shoots. Conditions that increase early growth rate postpone shoot tip abortion. PMID:17650513

  11. Resistance exercise volume affects myofibrillar protein synthesis and anabolic signalling molecule phosphorylation in young men

    PubMed Central

    Burd, Nicholas A; Holwerda, Andrew M; Selby, Keegan C; West, Daniel W D; Staples, Aaron W; Cain, Nathan E; Cashaback, Joshua G A; Potvin, James R; Baker, Steven K; Phillips, Stuart M

    2010-01-01

    We aimed to determine if any mechanistic differences exist between a single set (1SET) and multiple sets (i.e. 3 sets; 3SET) of resistance exercise by utilizing a primed constant infusion of [ring-13C6]phenylalanine to determine myofibrillar protein synthesis (MPS) and Western blot analysis to examine anabolic signalling molecule phosphorylation following an acute bout of resistance exercise. Eight resistance-trained men (24 ± 5 years, BMI = 25 ± 4 kg m−2) were randomly assigned to perform unilateral leg extension exercise at 70% concentric one repetition maximum (1RM) until volitional fatigue for 1SET or 3SET. Biopsies from the vastus lateralis were taken in the fasted state (Fast) and fed state (Fed; 20 g of whey protein isolate) at rest, 5 h Fed, 24 h Fast and 29 h Fed post-exercise. Fed-state MPS was transiently elevated above rest at 5 h for 1SET (2.3-fold) and returned to resting levels by 29 h post-exercise. However, the exercise induced increase in MPS following 3SET was superior in amplitude and duration as compared to 1SET at both 5 h (3.1-fold above rest) and 29 h post-exercise (2.3-fold above rest). Phosphorylation of 70 kDa S6 protein kinase (p70S6K) demonstrated a coordinated increase with MPS at 5 h and 29 h post-exercise such that the extent of p70S6K phosphorylation was related to the MPS response (r = 0.338, P = 0.033). Phosphorylation of 90 kDa ribosomal S6 protein kinase (p90RSK) and ribosomal protein S6 (rps6) was similar for 1SET and 3SET at 24 h Fast and 29 h Fed, respectively. However, 3SET induced a greater activation of eukaryotic translation initiation factor 2Bɛ (eIF2Bɛ) and rpS6 at 5 h Fed. These data suggest that 3SET of resistance exercise is more anabolic than 1SET and may lead to greater increases in myofibrillar protein accretion over time. PMID:20581041

  12. The effect of anabolic steroids on mandibular growth.

    PubMed

    Gebhardt, Alexander; Pancherz, Hans

    2003-04-01

    The aim of this study was to assess the effect of nandrolone (Deca-Durabolin, AKZO Nobel, Cambridge, United Kingdom) on mandibular growth in juvenile and adult rats with radiographic cephalometry and immunoradiology. Juvenile (n = 16) and adult (n = 16) inbred female Wistar-Kyoto rats were compared. Each group was divided into 2 subgroups with 8 experimental (E) and 8 control (C) animals in each subgroup. Lateral headfilms taken before and after the 70-day study period were analyzed. Body weight and blood serum IGF-I levels were monitored weekly. The results showed marked mandibular growth changes in both the juvenile and the adult E rats. Body weight increase was larger in the E than in the C animals. The IGF-I blood serum levels were similar in the juvenile E and C rats but higher in the adult E animals than in the adult C animals. It was found that the anabolic steroid (Deca-Durabolin) had a significant effect on mandibular growth in both juvenile and adult rats.

  13. Adverse health effects of anabolic-androgenic steroids.

    PubMed

    van Amsterdam, Jan; Opperhuizen, Antoon; Hartgens, Fred

    2010-06-01

    Anabolic-androgenic steroids (AAS) are synthetic drugs derived from testosterone. Illegally, these drugs are regularly self-administered by body builders and power lifters to enhance their sportive performance. Adverse side effects of AAS include sexual dysfunction, alterations of the cardiovascular system, psyche and behavior, and liver toxicity. However, severe side effects appear only following prolonged use of AAS at high dose and their occurrence is limited. Occasionally, AAS abuse may be linked to certain social and psychological traits of the user, like low self-esteem, low self-confidence, suffered hostility, childhood conduct disorder, and tendency to high-risk behavior. The overwhelming stereotype about AAS is that these compounds cause aggressive behavior in males. However, the underlying personality traits of a specific subgroup of the AAS abusers, who show aggression and hostility, may be relevant, as well. Use of AAS in combination with alcohol largely increases the risk of violence and aggression. The dependence liability of AAS is very low, and withdrawal effects are relatively mild. Based on the scores for acute and chronic adverse health effects, the prevalence of use, social harm and criminality, AAS were ranked among 19 illicit drugs as a group of drugs with a relatively low harm.

  14. Testing for anabolic steroids in hair from two bodybuilders.

    PubMed

    Kintz, P; Cirimele, V; Sachs, H; Jeanneau, T; Ludes, B

    1999-05-17

    Two male bodybuilders were recently arrested by the French customs in Strasbourg (France) in possession of 2050 tablets and 251 ampoules of various anabolic steroids. It was claimed that the steroids were for personal use and not for trafficing as suggested by the police. Urine and hair specimens were collected from both suspects to clarify the claims. Nandrolone, stanozolol, testosterone and their corresponding metabolites were identified in the urine of both subjects. After decontamination, the hair was hydrolyzed by sodium hydroxide in presence of deuterated internal standards. After extraction with ethyl acetate and silylation, the drugs were identified by GC-MS in the electron impact mode. Hair from both males were positive for nandrolone (196 and 260 pg/mg), testosterone (46 and 71 pg/mg) and stanozolol (135 and 156 pg/mg), clearly indicating steroids abuse. Although not yet recognized by the International Olympic Committee, hair analysis may be a useful adjunct to conventional drug testing in urine from athletes.

  15. Biochemistry and physiology of anabolic androgenic steroids doping.

    PubMed

    Lippi, G; Franchini, M; Banfi, G

    2011-05-01

    Anabolic Androgenic Steroids (AASs) are chemical and pharmacological derivatives of the male hormone testosterone which are widely used for increasing burst and sprinting activities in sports. Although AASs are thought to be transversal to the plurality of sports disciplines, they are principally misused by bodybuilders, weightlifters, shot, hammer, discus or javelin throwers, rugby and American football players as well as by swimmers and runners. AAS exert a kaleidoscope of effects on human biology, principally through the 5-α-reductase-mediated conversion into dihydrotestosterone, the aromatase-mediated conversion into female sex hormones, a competitive antagonism to the glucocorticoid receptors, the potential stimulation of erythropoietin secretion as well as psychoactive effects on the brain. The influence of AASs on physical performance is still undefined, since the large number of studies published so far have described discordant and often contradictory outcomes. Nevertheless, animal and human investigations support the hypothesis that the administration of AASs might increase lean body mass, muscle mass, and maximal voluntary strength especially in men, so that they would represent an appealing form of doping for increasing power capacity, sustaining intensive training periods and, last but not least, as a cosmetic muscle makeover. The aim of this article is to review the biochemistry, physiology and the ergogenic effects of AASs.

  16. Sudden or unnatural deaths involving anabolic-androgenic steroids.

    PubMed

    Darke, Shane; Torok, Michelle; Duflou, Johan

    2014-07-01

    Anabolic-androgenic steroids (AASs) are frequently misused. To determine causes of death, characteristics, toxicology, and pathology of AAS positive cases, all cases (n = 24) presenting to the New South Wales Department of Forensic Medicine (1995-2012) were retrieved. All were male, and the mean age was 31.7 years. Deaths were mainly due to accidental drug toxicity (62.5%), then suicide (16.7%) and homicide (12.5%). Abnormal testosterone/epitestosterone ratios were reported in 62.5%, followed by metabolites of nandrolone (58.3%), stanozolol (33.3%), and methandienone (20.8%). In 23 of 24 cases, substances other than steroids were detected, most commonly psychostimulants (66.7%). In nearly half, testicular atrophy was noted, as was testicular fibrosis and arrested spermatogenesis. Left ventricular hypertrophy was noted in 30.4%, and moderate to severe narrowing of the coronary arteries in 26.1%. To summarize, the typical case was a male polydrug user aged in their thirties, with death due to drug toxicity. Extensive cardiovascular disease was particularly notable.

  17. Synthetic anabolic agents: steroids and nonsteroidal selective androgen receptor modulators.

    PubMed

    Thevis, Mario; Schänzer, Wilhelm

    2010-01-01

    The central role of testosterone in the development of male characteristics, as well as its beneficial effects on physical performance and muscle growth, has led to the search for synthetic alternatives with improved pharmacological profiles. Hundreds of steroidal analogs have been prepared with a superior oral bioavailability, which should also possess reduced undesirable effects. However, only a few entered the pharmaceutical market due to severe toxicological incidences that were mainly attributed to the lack of tissue selectivity. Prominent representatives of anabolic-androgenic steroids (AAS) are for instance methyltestosterone, metandienone and stanozolol, which are discussed as model compounds with regard to general pharmacological aspects of synthetic AAS. Recently, nonsteroidal alternatives to AAS have been developed that selectively activate the androgen receptor in either muscle tissue or bones. These so-called selective androgen receptor modulators (SARMs) are currently undergoing late clinical trials (IIb) and will be prohibited by the World Anti-Doping Agency from January 2008. Their entirely synthetic structures are barely related to steroids, but particular functional groups allow for the tissue-selective activation or inhibition of androgen receptors and, thus, the stimulation of muscle growth without the risk of severe undesirable effects commonly observed in steroid replacement therapies. Hence, these compounds possess a high potential for misuse in sports and will be the subject of future doping control assays.

  18. [Doping--anabolic steroid abuse--careless homicide].

    PubMed

    Schneider, V; Klug, E

    1996-06-01

    Proceeding from a case requiring an expert's opinion (competitive athlete from the GDR), the question of damage to the health after the abuse of anabolic preparations is being discussed once again. In this connection, however, it is not only necessary to look at the cases that have come to light in the competitive sports sector (doping) but also at cases involving the body-building movement. Damages to the liver, in particular liver tumors, are described, among others. But vascular diseases are also described. Auto-aggression and aggression toward others can, however, also entail a forensic/psychiatric report, and, finally, the forensic-medicine expert can be challenged when manipulations of the urine specimens to be examined are involved (DNA analyses). From the legal point of view, doping cases will constantly pose the question of whether the athletes concerned knew what they were being "treated" with. Quite apart from forensic questions, however, it will also be necessary to discuss the overall complex from the point of view of medical ethics. Every time a case becomes known, damage is done once again to the idea that sports are supposed to bring nations together and promote peace.

  19. A systematic review of the key factors affecting tissue viability and rehabilitation outcomes of the residual limb in lower extremity traumatic amputees.

    PubMed

    Butler, Katrina; Bowen, Catherine; Hughes, Ann-Marie; Torah, Russel; Ayala, Ivo; Tudor, John; Metcalf, Cheryl D

    2014-08-01

    Most traumatic lower limb amputees ambulate using a prosthetic limb. Comfort, appearance of the missing limb and function are confirmed as being important during rehabilitation post-amputation. Emerging evidence suggests that impaired tissue viability of the stump affects rehabilitation and thus clinical ability to provide optimum care. The primary objective of this systematic review was to identify key factors relating to tissue viability of the residual limb in lower extremity traumatic amputees. A secondary objective was to identify factors that affect rehabilitation post-amputation. In total, 218 studies were assessed; 37 met pre-determined criteria. Studies were classified according to the WHO ICF framework and the NHMRC level of evidence. Five key themes emerged; Prosthetic Fit; The Residuum; Quality of Life; Amputee Care and Prosthetic Use. The evidence indicates that high frequencies of skin problems affecting tissue viability within this population are inherently linked to intolerance of the prosthesis. Stump integrity, amputee care regimen and pain were also identified as impacting on quality of life, affecting rehabilitation and the ability to become independently mobile. Levels of evidence within all studies were low and indicative of the majority being non-randomised cohort studies or case-control studies. As there are a limited number of interventional studies, further development of robust outcome measures, clinical trials and prospective studies are of utmost importance to unravel the links between tissue viability and the other key factors. This will inform clinical management strategies and help develop targeted therapies and care pathways.

  20. Factors Impacting Student Service Utilization at Ontario Colleges: Key Performance Indicators as a Measure of Success: A Niagara College View

    ERIC Educational Resources Information Center

    Veres, David

    2015-01-01

    Student success in Ontario College is significantly influenced by the utilization of student services. At Niagara College there has been a significant investment in student services as a strategy to support student success. Utilizing existing KPI data, this quantitative research project is aimed at measuring factors that influence both the use of…

  1. Aging is a primary risk factor for cardiac arrhythmias: disruption of intracellular Ca2+ regulation as a key suspect.

    PubMed

    Hatch, Fiona; Lancaster, Matthew K; Jones, Sandra A

    2011-08-01

    Aging is an inevitable time-dependent progression associated with a functional decline of the cardiovascular system even in 'healthy' individuals. Age positively correlates with an increasing risk of cardiac problems including arrhythmias. Not only the prevalence but also the severity of arrhythmias escalates with age. The reasons for this are multifactorial but dysregulation of intracellular calcium within the heart is likely to play a key role in initiating and perpetuating these life-threatening events. We now know that several aspects of cardiac calcium regulation significantly change with advancing age - changes that could produce electrical instability. Further development of knowledge of the mechanisms underlying these changes will allow us to reduce what currently is an inevitable increase in the incidence of arrhythmias in the elderly.

  2. Life cycle assessment of lignocellulosic ethanol: a review of key factors and methods affecting calculated GHG emissions and energy use.

    PubMed

    Gerbrandt, Kelsey; Chu, Pei Lin; Simmonds, Allison; Mullins, Kimberley A; MacLean, Heather L; Griffin, W Michael; Saville, Bradley A

    2016-04-01

    Lignocellulosic ethanol has potential for lower life cycle greenhouse gas emissions compared to gasoline and conventional grain-based ethanol. Ethanol production 'pathways' need to meet economic and environmental goals. Numerous life cycle assessments of lignocellulosic ethanol have been published over the last 15 years, but gaps remain in understanding life cycle performance due to insufficient data, and model and methodological issues. We highlight key aspects of these issues, drawing on literature and a case study of corn stover ethanol. Challenges include the complexity of feedstock/ecosystems and market-mediated aspects and the short history of commercial lignocellulosic ethanol facilities, which collectively have led to uncertainty in GHG emissions estimates, and to debates on LCA methods and the role of uncertainty in decision making.

  3. Where to Forage in the Absence of Sea Ice? Bathymetry As a Key Factor for an Arctic Seabird.

    PubMed

    Amélineau, Françoise; Grémillet, David; Bonnet, Delphine; Le Bot, Tangi; Fort, Jérôme

    2016-01-01

    The earth is warming at an alarming rate, especially in the Arctic, where a marked decline in sea ice cover may have far-ranging consequences for endemic species. Little auks, endemic Arctic seabirds, are key bioindicators as they forage in the marginal ice zone and feed preferentially on lipid-rich Arctic copepods and ice-associated amphipods sensitive to the consequences of global warming. We tested how little auks cope with an ice-free foraging environment during the breeding season. To this end, we took advantage of natural variation in sea ice concentration along the east coast of Greenland. We compared foraging and diving behaviour, chick diet and growth and adult body condition between two years, in the presence versus nearby absence of sea ice in the vicinity of their breeding site. Moreover, we sampled zooplankton at sea when sea ice was absent to evaluate prey location and little auk dietary preferences. Little auks foraged in the same areas both years, irrespective of sea ice presence/concentration, and targeted the shelf break and the continental shelf. We confirmed that breeding little auks showed a clear preference for larger copepod species to feed their chick, but caught smaller copepods and nearly no ice-associated amphipod when sea ice was absent. Nevertheless, these dietary changes had no impact on chick growth and adult body condition. Our findings demonstrate the importance of bathymetry for profitable little auk foraging, whatever the sea-ice conditions. Our investigations, along with recent studies, also confirm more flexibility than previously predicted for this key species in a warming Arctic.

  4. The ORCA2 transcription factor plays a key role in regulation of the terpenoid indole alkaloid pathway

    PubMed Central

    2013-01-01

    Background The terpenoid indole alkaloid (TIA) pathway leads to the production of pharmaceutically important drugs, such as the anticancer compounds vinblastine and vincristine. Unfortunately, these drugs are produced in trace amounts, causing them to be very costly. To increase production of these drugs, an improved understanding of the TIA regulatory pathway is needed. Towards this end, transgenic Catharanthus roseus hairy roots that overexpress the ORCA2 TIA transcriptional activator were generated and characterized. Results Transcriptional profiling experiments revealed that overexpression of ORCA2 results in altered expression of key genes from the indole and terpenoid pathways, which produce precursors for the TIA pathway, and from the TIA pathway itself. In addition, metabolite-profiling experiments revealed that overexpression of ORCA2 significantly affects the levels of several TIA metabolites. ORCA2 overexpression also causes significant increases in transcript levels of several TIA regulators, including TIA transcriptional repressors. Conclusions Results presented here indicate that ORCA2 plays a critical role in regulation of TIA metabolism. ORCA2 regulates expression of key genes from both feeder pathways, as well as the genes (STR and SGD) encoding the enzymes that catalyze the first two steps in TIA biosynthesis. ORCA2 may play an especially important role in regulation of the downstream branches of the TIA pathway, as it regulates four out of five genes characterized from this part of the pathway. Regulation of TIA transcriptional repressors by ORCA2 may provide a mechanism whereby increases in TIA metabolite levels in response to external stimuli are transient and limited in magnitude. PMID:24099172

  5. Where to Forage in the Absence of Sea Ice? Bathymetry As a Key Factor for an Arctic Seabird

    PubMed Central

    Amélineau, Françoise; Grémillet, David; Bonnet, Delphine; Le Bot, Tangi; Fort, Jérôme

    2016-01-01

    The earth is warming at an alarming rate, especially in the Arctic, where a marked decline in sea ice cover may have far-ranging consequences for endemic species. Little auks, endemic Arctic seabirds, are key bioindicators as they forage in the marginal ice zone and feed preferentially on lipid-rich Arctic copepods and ice-associated amphipods sensitive to the consequences of global warming. We tested how little auks cope with an ice-free foraging environment during the breeding season. To this end, we took advantage of natural variation in sea ice concentration along the east coast of Greenland. We compared foraging and diving behaviour, chick diet and growth and adult body condition between two years, in the presence versus nearby absence of sea ice in the vicinity of their breeding site. Moreover, we sampled zooplankton at sea when sea ice was absent to evaluate prey location and little auk dietary preferences. Little auks foraged in the same areas both years, irrespective of sea ice presence/concentration, and targeted the shelf break and the continental shelf. We confirmed that breeding little auks showed a clear preference for larger copepod species to feed their chick, but caught smaller copepods and nearly no ice-associated amphipod when sea ice was absent. Nevertheless, these dietary changes had no impact on chick growth and adult body condition. Our findings demonstrate the importance of bathymetry for profitable little auk foraging, whatever the sea-ice conditions. Our investigations, along with recent studies, also confirm more flexibility than previously predicted for this key species in a warming Arctic. PMID:27438790

  6. Anabolic-Androgenic Steroid Use Among California Community College Student-Athletes

    PubMed Central

    Kersey, Robert D.

    1996-01-01

    Objective: To determine the incidence of anabolic- androgenic steroid use among a sample of community college student-athletes; also, to compare various aspects of users and nonusers, as well as to describe usage patterns. Design and Setting: A survey following random stratified cluster sampling techniques was administered to 10 California community colleges. Subjects: A group of 1,185 male and female student- athletes. Measurements: An anonymous 27-item, valid, and reliable questionnaire was administered surveying anabolic-androgenic steroid use and usage patterns. Results: Of all student-athletes sampled, 3.3% were anabolic -androgenic steroid users. Gender-specific incidence rates were 4.2% for males and 1.2% for females. Anabolic- androgenic steroid users tended to be older males, usually in their second year of college. The users were more often minorities. Users believed that they were knowledgeable about anabolic-androgenic steroids, and that the rates of usage were higher than reported. Their sources of steroid information were often lifting partners and fellow athletes. Use of these drugs was most often in cycles (mean of 6.7 weeks) and was frequently done using multiple anabolic-androgenic steroids at a time. The average number of cycles completed was 2.9. A wide variety of steroids were used by the student-athletes, of which most were obtained from illegal sources. Conclusions: Anabolic-androgenic steroid use among Califonia community college student-athletes were similar to other previous research studies involving high school and university student-athletes. PMID:16558405

  7. Media exposure, mediated social comparison to idealized images of muscularity, and anabolic steroid use.

    PubMed

    Melki, Jad P; Hitti, Eveline A; Oghia, Michael J; Mufarrij, Afif A

    2015-01-01

    This study examined the association between anabolic-androgenic steroid (AAS) use and dominant sociocultural factors, specifically media exposure to idealized images of male muscularity, and mediated social comparison trends among a sample of young Arab adults. The study found evidence that participants more exposed to content that promotes muscularity and those who idealize images of muscularity and perceive them as motivators for achieving muscularity are more likely to be AAS users. It also found that a significant percentage of participants used at least one kind of dietary supplement and that the level of AAS use among health club participants indicates it is a significant public health problem in Lebanon. The study suggests that dealing with this problem requires a unique approach, beyond the typical awareness of risks strategy, since some users were well aware of the risks yet continue to use AAS, and their motivations pertain more to body image and sexuality. A stronger approach that utilizes critical media literacy teaching that ingrains these issues into school and university curricula will have a more lasting impact.

  8. Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate*

    PubMed Central

    Thaler, Roman; Maurizi, Antonio; Roschger, Paul; Sturmlechner, Ines; Khani, Farzaneh; Spitzer, Silvia; Rumpler, Monika; Zwerina, Jochen; Karlic, Heidrun; Dudakovic, Amel; Klaushofer, Klaus; Teti, Anna; Rucci, Nadia; Varga, Franz; van Wijnen, Andre J.

    2016-01-01

    Bone degenerative pathologies like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Here we show that sulforaphane (SFN), a naturally occurring isothiocyanate, promotes osteoblast differentiation by epigenetic mechanisms. SFN enhances active DNA demethylation via Tet1 and Tet2 and promotes preosteoblast differentiation by enhancing extracellular matrix mineralization and the expression of osteoblastic markers (Runx2, Col1a1, Bglap2, Sp7, Atf4, and Alpl). SFN decreases the expression of the osteoclast activator receptor activator of nuclear factor-κB ligand (RANKL) in osteocytes and mouse calvarial explants and preferentially induces apoptosis in preosteoclastic cells via up-regulation of the Tet1/Fas/Caspase 8 and Caspase 3/7 pathway. These mechanistic effects correlate with higher bone volume (∼20%) in both normal and ovariectomized mice treated with SFN for 5 weeks compared with untreated mice as determined by microcomputed tomography. This effect is due to a higher trabecular number in these mice. Importantly, no shifts in mineral density distribution are observed upon SFN treatment as measured by quantitative backscattered electron imaging. Our data indicate that the food-derived compound SFN epigenetically stimulates osteoblast activity and diminishes osteoclast bone resorption, shifting the balance of bone homeostasis and favoring bone acquisition and/or mitigation of bone resorption in vivo. Thus, SFN is a member of a new class of epigenetic compounds that could be considered for novel strategies to counteract osteoporosis. PMID:26757819

  9. Bone marrow oxytocin mediates the anabolic action of estrogen on the skeleton.

    PubMed

    Colaianni, Graziana; Sun, Li; Di Benedetto, Adriana; Tamma, Roberto; Zhu, Ling-Ling; Cao, Jay; Grano, Maria; Yuen, Tony; Colucci, Sylvia; Cuscito, Concetta; Mancini, Lucia; Li, Jianhua; Nishimori, Katsuhiko; Bab, Itai; Lee, Heon-Jin; Iqbal, Jameel; Young, W Scott; Rosen, Clifford; Zallone, Alberta; Zaidi, Mone

    2012-08-17

    Estrogen uses two mechanisms to exert its effect on the skeleton: it inhibits bone resorption by osteoclasts and, at higher doses, can stimulate bone formation. Although the antiresorptive action of estrogen arises from the inhibition of the MAPK JNK, the mechanism of its effect on the osteoblast remains unclear. Here, we report that the anabolic action of estrogen in mice occurs, at least in part, through oxytocin (OT) produced by osteoblasts in bone marrow. We show that the absence of OT receptors (OTRs) in OTR(-/-) osteoblasts or attenuation of OTR expression in silenced cells inhibits estrogen-induced osteoblast differentiation, transcription factor up-regulation, and/or OT production in vitro. In vivo, OTR(-/-) mice, known to have a bone formation defect, fail to display increases in trabecular bone volume, cortical thickness, and bone formation in response to estrogen. Furthermore, osteoblast-specific Col2.3-Cre(+)/OTR(fl/fl) mice, but not TRAP-Cre(+)/OTR(fl/fl) mice, mimic the OTR(-/-) phenotype and also fail to respond to estrogen. These data attribute the phenotype of OTR deficiency to an osteoblastic rather than an osteoclastic defect. Physiologically, feed-forward OT release in bone marrow by a rising estrogen concentration may facilitate rapid skeletal recovery during the latter phases of lactation.

  10. Anabolic-androgenic steroid use among young male and female athletes: is the game to blame?

    PubMed

    Harmer, P A

    2010-01-01

    The use of anabolic-androgenic steroids (AAS) by young athletes has been a primary concern of sports governing bodies because of the implications for unfair advantage in performance and the potential for adverse side effects. Research over several decades indicated a lifetime prevalence of AAS use for adolescent males of 4-6% and for females of 1.5-3%, indicating a problem involving millions of athletes and a potential epidemic of AAS-related pathologies. However, recent studies have questioned the presumption that participation in organised sport is the primary risk factor for AAS use in adolescents as well as the extant estimates of the magnitude of the problem. Increasing evidence indicates that AAS use is associated with non-athletes and is linked to a broader syndrome of problem behaviours rather than efforts to achieve sporting success, and that sports participation may be protective against AAS use. Moreover, employing lifetime prevalence to gauge AAS use limits accurate evaluation of the personal and public health risk as the majority of respondents are not habitual users. Previous studies may have also inflated prevalence values through ambiguously worded survey questions and other design flaws, and few data are available on actual dosages. Prevention efforts need to be focused beyond organised sport and target the general adolescent population rather than athletes and should be founded on interventions with demonstrated efficacy for delinquent, antisocial and self-destructive behaviours rather than the ethical imperative of fair play.

  11. Individual and Population Level Impact of Key HIV Risk Factors on HIV Incidence Rates in Durban, South Africa

    PubMed Central

    Ramjee, Gita; Moonsamy, Suri; Abbai, Nathlee Samantha; Wand, Handan

    2016-01-01

    We aimed to estimate the individual and joint impact of age, marital status and diagnosis with sexually transmitted infections (STIs) on HIV acquisition among young women at a population level in Durban, KwaZulu-Natal, South Africa. A total of 3,978 HIV seronegative women were recruited for four biomedical intervention trials from 2002–2009. Point and interval estimates of partial population attributable risk (PAR) were used to quantify the proportion of HIV seroconversions which can be prevented if a combination of risk factors is eliminated from a target population. More than 70% of the observed HIV acquisitions were collectively attributed to the three risk factors: younger age (<25 years old), unmarried and not cohabiting with a stable/regular partner and diagnosis with STIs. Addressing these risks requires targeted structural, behavioural, biomedical and cultural interventions in order to impact on unacceptably high HIV incidence rates among young women and the population as a whole. PMID:27104835

  12. Key Factors Controlling the Growth of Biological Soil Crusts: Towards a Protocol to Produce Biocrusts in Greenhouse Facilities

    NASA Astrophysics Data System (ADS)

    Velasco Ayuso, Sergio; María Giraldo Silva, Ana; Nelson, Corey; Barger, Nichole; Antoninka, Anita; Bowker, Matthew; Garcia-Pichel, Ferran

    2016-04-01

    Biological soil crusts (= biocrusts) are topsoil communities comprise of, but not limited to, cyanobacteria, algae, lichens, and mosses that grow intimately associated with soil particles in drylands. Biocrusts have central ecological roles in these areas as sources of carbon and nutrients, and efficiently retain water and prevent soil erosion, which improves soil structure and promotes soil fertility. However, human activities, such as cattle grazing, hiking or military training, are rapidly striking biocrusts. Although it is well known that the inoculation with cyanobacteria or lichens can enhance the recovery of biocrusts in degraded soils, little is known about the factors that control their growth rates. Using soil and inocula from four different sites located in one cold desert (Utah) and in one hot desert (New Mexico), we performed a fractional factorial experiment involving seven factors (water, light, P, N, calcium carbonate, trace metals and type of inoculum) to screen their effects on the growth of biocrusts. After four months, we measured the concentration of chlorophyll a, and we discovered that water, light and P, N or P+N were the most important factors controlling the growth of biocrusts. In the experimental treatments involving these three factors we measured a similar concentration of chlorophyll a (or even higher) to this found in the field locations. Amplification of the 16S rRNA gene segment using universal bacteria primers revealed a microbial community composition in the biocrusts grown that closely corresponds to initial measurements made on inocula. In summary, based on our success in obtaining biocrust biomass from natural communities in greenhouse facilities, without significantly changing its community composition at the phylum and cyanobacterial level, we are paving the road to propose a protocol to produce a high quality-nursed inoculum aiming to assist restoration of arid and semi-arid ecosystems affected by large-scale disturbances.

  13. PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1): A KEY FACTOR LINKING FIBRINOLYSIS AND AGE-RELATED SUBCLINICAL AND CLINICAL CONDITIONS

    PubMed Central

    Cesari, Matteo; Pahor, Marco; Incalzi, Raffaele Antonelli

    2010-01-01

    The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age-related development of a pro-thrombotic imbalance in the fibrinolysis homeostasis has been hypothesized at the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the resulting of the interactions among multiple plasminogen activators and inhibitors constituing the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. Plasminogen activator inhibitor-1 (PAI-1) is a member of the superfamily of serine-protease inhibitors (or serpins), and the principal inhibitor of both the tissue-type and the urinary-type plasminogen activator, the two plasminogen activators able to activate plasminogen. In this review, current evidence describing the central role played by PAI-1 in a number of age-related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. Despite some controversial and unclear issues, PAI-1 represents an extremely promising marker which may become a biological parameter to be growingly considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age-related conditions in the next future. PMID:20626406

  14. STAT5 is a key transcription factor for IL-3-mediated inhibition of RANKL-induced osteoclastogenesis

    PubMed Central

    Lee, Jongwon; Seong, Semun; Kim, Jung Ha; Kim, Kabsun; Kim, Inyoung; Jeong, Byung-chul; Nam, Kwang-Il; Kim, Kyung Keun; Hennighausen, Lothar; Kim, Nacksung

    2016-01-01

    Among the diverse cytokines involved in osteoclast differentiation, interleukin (IL)-3 inhibits RANKL-induced osteoclastogenesis. However, the mechanism underlying IL-3-mediated inhibition of osteoclast differentiation is not fully understood. Here we demonstrate that the activation of signal transducers and activators of transcription 5 (STAT5) by IL-3 inhibits RANKL-induced osteoclastogenesis through the induction of the expression of Id genes. We found that STAT5 overexpression inhibited RANKL-induced osteoclastogenesis. However, RANKL did not regulate the expression or activation of STAT5 during osteoclast differentiation. STAT5 deficiency prevented IL-3-mediated inhibition of osteoclastogenesis, suggesting a key role of STAT5 in IL-3-mediated inhibition of osteoclast differentiation. In addition, IL-3-induced STAT5 activation upregulated the expression of Id1 and Id2, which are negative regulators of osteoclastogenesis. Overexpression of ID1 or ID2 in STAT5-deficient cells reversed osteoclast development recovered from IL-3-mediated inhibition. Importantly, microcomputed tomography and histomorphometric analysis revealed that STAT5 conditional knockout mice showed reduced bone mass, with an increased number of osteoclasts. Furthermore, IL-3 inhibited RANKL-induced osteoclast differentiation less effectively in the STAT5 conditional knockout mice than in the wild-type mice after RANKL injection. Taken together, our findings indicate that STAT5 contributes to the remarkable IL-3-mediated inhibition of RANKL-induced osteoclastogenesis by activating Id genes and their associated pathways. PMID:27485735

  15. Identification of the key weather factors affecting overwintering success of Apolygus lucorum eggs in dead host tree branches.

    PubMed

    Pan, Hongsheng; Liu, Bing; Lu, Yanhui; Desneux, Nicolas

    2014-01-01

    Understanding the effects of weather on insect population dynamics is crucial to simulate and forecast pest outbreaks, which is becoming increasingly important with the effects of climate change. The mirid bug Apolygus lucorum is an important pest on cotton, fruit trees and other crops in China, and primarily lays its eggs on dead parts of tree branches in the fall for subsequent overwintering. As such, the eggs that hatch the following spring are most strongly affected by ambient weather factors, rather than by host plant biology. In this study, we investigated the effects of three major weather factors: temperature, relative humidity and rainfall, on the hatching rate of A. lucorum eggs overwintering on dead branches of Chinese date tree (Ziziphus jujuba). Under laboratory conditions, rainfall (simulated via soaking) was necessary for the hatching of overwintering A. lucorum eggs. In the absence of rainfall (unsoaked branches), very few nymphs successfully emerged under any of the tested combinations of temperature and relative humidity. In contrast, following simulated rainfall, the hatching rate of the overwintering eggs increased dramatically. Hatching rate and developmental rate were positively correlated with relative humidity and temperature, respectively. Under field conditions, the abundance of nymphs derived from overwintering eggs was positively correlated with rainfall amount during the spring seasons of 2009-2013, while the same was not true for temperature and relative humidity. Overall, our findings indicate that rainfall is the most important factor affecting the hatching rate of overwintering A. lucorum eggs on dead plant parts and nymph population levels during the spring season. It provides the basic information for precisely forecasting the emergence of A. lucorum and subsequently timely managing its population in spring, which will make it possible to regional control of this insect pest widely occurring in multiple crops in summer.

  16. Identification of the Key Weather Factors Affecting Overwintering Success of Apolygus lucorum Eggs in Dead Host Tree Branches

    PubMed Central

    Pan, Hongsheng; Liu, Bing; Lu, Yanhui; Desneux, Nicolas

    2014-01-01

    Understanding the effects of weather on insect population dynamics is crucial to simulate and forecast pest outbreaks, which is becoming increasingly important with the effects of climate change. The mirid bug Apolygus lucorum is an important pest on cotton, fruit trees and other crops in China, and primarily lays its eggs on dead parts of tree branches in the fall for subsequent overwintering. As such, the eggs that hatch the following spring are most strongly affected by ambient weather factors, rather than by host plant biology. In this study, we investigated the effects of three major weather factors: temperature, relative humidity and rainfall, on the hatching rate of A. lucorum eggs overwintering on dead branches of Chinese date tree (Ziziphus jujuba). Under laboratory conditions, rainfall (simulated via soaking) was necessary for the hatching of overwintering A. lucorum eggs. In the absence of rainfall (unsoaked branches), very few nymphs successfully emerged under any of the tested combinations of temperature and relative humidity. In contrast, following simulated rainfall, the hatching rate of the overwintering eggs increased dramatically. Hatching rate and developmental rate were positively correlated with relative humidity and temperature, respectively. Under field conditions, the abundance of nymphs derived from overwintering eggs was positively correlated with rainfall amount during the spring seasons of 2009–2013, while the same was not true for temperature and relative humidity. Overall, our findings indicate that rainfall is the most important factor affecting the hatching rate of overwintering A. lucorum eggs on dead plant parts and nymph population levels during the spring season. It provides the basic information for precisely forecasting the emergence of A. lucorum and subsequently timely managing its population in spring, which will make it possible to regional control of this insect pest widely occurring in multiple crops in summer. PMID

  17. Contextual factors as a key to understanding the heterogeneity of effects of a maternal health policy in Burkina Faso?

    PubMed Central

    Belaid, Loubna; Ridde, Valéry

    2015-01-01

    Burkina Faso implemented a national subsidy for emergency obstetric and neonatal care (EmONC) covering 80% of the cost of normal childbirth in public health facilities. The objective was to increase coverage of facility-based deliveries. After implementation of the EmONC policy, coverage increased across the country, but disparities were observed between districts and between primary healthcare centres (PHC). To understand the variation in coverage, we assessed the contextual factors and the implementation of EmONC in six PHCs in a district. We conducted a contrasted multiple case study. We interviewed women (n = 71), traditional birth attendants (n = 7), clinic management committees (n = 11), and health workers and district health managers (n = 26). Focus groups (n = 62) were conducted within communities. Observations were carried out in the six PHCs. Implementation was nearly homogeneous in the six PHCs but the contexts and human factors appeared to explain the variations observed on the coverage of facility-based deliveries. In the PHCs of Nogo and Tara, the immediate increase in coverage was attributed to health workers’ leadership in creatively promoting facility-based deliveries and strengthening relationships of trust with communities, users’ positive perceptions of quality of care and the arrival of female professional staff. The change of healthcare team at Iata’s PHC and a penalty fee imposed for home births in Belem may have caused the delayed effects there. Finally, the unchanged coverage in the PHCs of Fati and Mata was likely due to lack of promotion of facility-based deliveries, users’ negative perceptions of quality of care, and conflicts between health workers and users. Before implementation, decision-makers should perform pilot studies to adapt policies according to contexts and human factors. PMID:24633914

  18. Exploring key factors in the choice of e-health using an asthma care mobile service model.

    PubMed

    Lin, Shu-Ping; Yang, Hung-Yu

    2009-11-01

    Asthma care mobile service (ACMS) is a care platform for asthma patients using mobile phones to monitor asthma patients' real-time conditions. The anticipated benefits and development of the healthcare network platform rely on people's adoptive willingness and behavioral intention. The goal of this study is to understand and predict patients' acceptance behavior for ACMS as an application of e-health. The study is based on the technology acceptance model and integrates "subjective norm" and "innovativeness" to understand and predict the patient's attitude and behavioral intention. Employing a convenience sampling method, valid questionnaire responses were obtained from 229 patients. A confirmatory factor analysis examined the reliability and validity of the measurement model, while the structural equation modeling technique was employed to interpret the causal model. The model was used in the study to explain and predict the utilization of ACMS with a high explanatory power as a good-fit model. The results indicated the most critical factor that affects behavioral intentions related to ACMS is user attitude, followed by perceived usefulness, subjective norm, perceived ease of use, and innovativeness. The results provide the government developing high-tech, preventive medicine strategies the necessary data to define an appropriate policy to use in attracting greater participation in the effort.

  19. IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain

    PubMed Central

    Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

    2016-01-01

    The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

  20. Ikaros could be a key factor in the maintenance of "B-side" of B-1 cells.

    PubMed

    Oliveira, Vivian Cristina; Moretti, Nilmar Silvo; Augusto, Leonardo da Silva; Schenkman, Sergio; Mariano, Mario; Popi, Ana Flavia

    2015-11-01

    Ikaros, a zinc finger transcription factor, is an important regulator of the hematopoietic system. Several studies have suggested the role of Ikaros in the development, maturation, activation and differentiation of lymphocytes. To elucidate this mechanism, it is important to understand how this transcription factor works in the dichotomy of the hematopoietic system, a topic that remains uncertain. Herein, we investigated the role of Ikaros in the control of the lymphomyeloid phenotype of B-1 lymphocytes. We found that Ikaros, as well as its target genes, are expressed in B-1 cells,. Moreover, Ikaros positively regulates the expression of Flt3, Gfi and Il7r, while it down-regulates PU.1. During the induction of differentiation of B-1 cells toward phagocytes, Ikaros transcription was reduced. Taken together, these data pointed to the relevance of Ikaros in the maintenance of the promiscuous gene profile of B-1 cells. It could be suggested that Ikaros functions as a guardian of B-1 lymphoid pattern, and that its absence directs the differentiation of B-1 cells into phagocytes.

  1. Participation a Key Factor for Life Recovery After Disaster: A Grounded Theory Study in an Iranian Context

    PubMed Central

    Nakhaei, Maryam; Khankeh, Hamid Reza; Masoumi, Gholam Reza; Hosseini, Mohammad Ali; Parsa-Yekta, Zohreh

    2016-01-01

    Background Since life recovery after disasters is a subjective and multifaceted construct influenced by different factors, and survivors’ main concerns and experiences are not clear, the researchers intended to explore this process. Materials and Methods This study was conducted in 2011 - 2014 based on the grounded theory approach. Participants were selected by purposeful sampling followed by theoretical sampling to achieve conceptual and theoretical saturation. Data were collected through interviews, observation, focus group discussion, and document reviews. Data were analyzed by Strauss and Corbin’s (2008) recommended approach. Results Transcribed data from 26 interviews (managers, health care providers, and receivers), field notes, and other documents were analyzed, and 1,652 open codes were identified. The codes were categorized, using constant comparative analysis, into five main categories including reactive exposure, subsiding emotions, need for comprehensive health recovery, improvement of normalization (new normality achievement), and contextual factors. The process of life recovery after disaster was also explored. Conclusions The results clarified a deep perception of participants’ experiences after disaster. The path of life recovery after disasters involves participants’ striving to achieve a comprehensive health recovery, which starts with the need for all-inclusive health recovery as a main concern; this is the motivator for a responding strategy. This strategy is participatory, and the process is progressive; achievement of a new normality is the final goal, with new development and levels of empowerment. PMID:27703797

  2. Widespread pain and depression are key modifiable risk factors associated with reduced social participation in older adults

    PubMed Central

    Wilkie, Ross; Blagojevic-Bucknall, Milisa; Belcher, John; Chew-Graham, Carolyn; Lacey, Rosie J.; McBeth, John

    2016-01-01

    Abstract In older adults, reduced social participation increases the risk of poor health-related quality of life, increased levels of inflammatory markers and cardiovascular disease, and increased mortality. Older adults frequently present to primary care, which offers the potential to deliver interventions at the point of care to increase social participation. The aim of this prospective study was to identify the key modifiable exposures that were associated with reduced social participation in a primary care population of older adults. The study was a population-based prospective cohort study. Participants (n = 1991) were those aged ≥65 years who had completed questionnaires at baseline, and 3 and 6-year follow-ups. Generalized linear mixed modeling framework was used to test for associations between exposures and decreasing social participation over 6 years. At baseline, 44% of participants reported reduced social participation, increasing to 49% and 55% at 3 and 6-year follow-up. Widespread pain and depression had the strongest independent association with reduced social participation over the 6-year follow-up period. The prevalence of reduced social participation for those with widespread pain was 106% (adjusted incidence rate ratio 2.06, 95% confidence interval 1.72, 2.46), higher than for those with no pain. Those with depression had an increased prevalence of 82% (adjusted incidence rate ratio 1.82, 95% confidence interval 1.62, 2.06). These associations persisted in multivariate analysis. Population ageing will be accompanied by increasing numbers of older adults with pain and depression. Future trials should assess whether screening for widespread pain and depression, and targeting appropriate treatment in primary care, increase social participation in older people. PMID:27495019

  3. Immunological and structural relatedness of catabolic ornithine carbamoyltransferases and the anabolic enzymes of enterobacteria.

    PubMed Central

    Falmagne, P; Portetelle, D; Stalon, V

    1985-01-01

    Purified catabolic ornithine carbamoyltransferase of Pseudomonas putida and anabolic ornithine carbamoyltransferase (argF product) of Escherichia coli K-12 were used to prepare antisera. The two specific antisera gave heterologous cross-reactions of various intensities with bacterial catabolic ornithine carbamoyltransferases formed by Pseudomonas and representative organisms of other bacterial genera. The immunological cross-reactivity observed only between the catabolic ornithine carbamoyltransferases and the anabolic enzymes of enterobacteria suggests that these proteins share some structural similarities. Indeed, the amino acid composition of the anabolic ornithine carbamoyltransferase of E. coli K-12 (argF and argI products) closely resembles the amino acid compositions of the catabolic enzymes of Pseudomonas putida, Aeromonas formicans, Streptococcus faecalis, and Bacillus licheniformis. Comparison of the N-terminal amino acid sequence of the E. coli anabolic ornithine carbamoyltransferase with that of the A. formicans and Pseudomonas putida catabolic enzymes shows, respectively, 45 and 28% identity between the compared positions; the A. formicans sequence reveals 53% identity with the Pseudomonas putida sequence. These results favor the conclusion that anabolic ornithine carbamoyltransferases of enterobacteria and catabolic ornithine carbamoyltransferases derive from a common ancestral gene. PMID:3968036

  4. Chronic Drought Decreases Anabolic and Catabolic BVOC Emissions of Quercus pubescens in a Mediterranean Forest

    PubMed Central

    Saunier, Amélie; Ormeño, Elena; Wortham, Henri; Temime-Roussel, Brice; Lecareux, Caroline; Boissard, Christophe; Fernandez, Catherine

    2017-01-01

    Biogenic volatile organic compounds (BVOC) emitted by plants can originate from both anabolism (metabolite production through anabolic processes) and catabolism (metabolite degradation by oxidative reactions). Drought can favor leaf oxidation by increasing the oxidative pressure in plant cells. Thus, under the precipitation decline predicted for the Mediterranean region, it can be expected both strong oxidation of anabolic BVOC within leaves and, as a result, enhanced catabolic BVOC emissions. Using an experimental rain exclusion device in a natural forest, we compared the seasonal course of the emissions of the main anabolic BVOC released by Q. pubescens (isoprene and methanol) and their catabolic products (MACR+MVK+ISOPOOH and formaldehyde, respectively) after 3 years of precipitation restriction (−30% of rain). Thus, we assume that this repetitive amplified drought promoted a chronic drought. BVOC emissions were monitored, on-line, with a PTR-ToF-MS. Amplified drought decreased all BVOC emissions rates in spring and summer by around 40–50 %, especially through stomatal closure, with no effect in autumn. Moreover, ratios between catabolic and anabolic BVOC remained unchanged with amplified drought, suggesting a relative stable oxidative pressure in Q. pubescens under the water stress applied. Moreover, these results suggest a quite good resilience of this species under the most severe climate change scenario in the Mediterranean region. PMID:28228762

  5. Chronic Drought Decreases Anabolic and Catabolic BVOC Emissions of Quercus pubescens in a Mediterranean Forest.

    PubMed

    Saunier, Amélie; Ormeño, Elena; Wortham, Henri; Temime-Roussel, Brice; Lecareux, Caroline; Boissard, Christophe; Fernandez, Catherine

    2017-01-01

    Biogenic volatile organic compounds (BVOC) emitted by plants can originate from both anabolism (metabolite production through anabolic processes) and catabolism (metabolite degradation by oxidative reactions). Drought can favor leaf oxidation by increasing the oxidative pressure in plant cells. Thus, under the precipitation decline predicted for the Mediterranean region, it can be expected both strong oxidation of anabolic BVOC within leaves and, as a result, enhanced catabolic BVOC emissions. Using an experimental rain exclusion device in a natural forest, we compared the seasonal course of the emissions of the main anabolic BVOC released by Q. pubescens (isoprene and methanol) and their catabolic products (MACR+MVK+ISOPOOH and formaldehyde, respectively) after 3 years of precipitation restriction (-30% of rain). Thus, we assume that this repetitive amplified drought promoted a chronic drought. BVOC emissions were monitored, on-line, with a PTR-ToF-MS. Amplified drought decreased all BVOC emissions rates in spring and summer by around 40-50 %, especially through stomatal closure, with no effect in autumn. Moreover, ratios between catabolic and anabolic BVOC remained unchanged with amplified drought, suggesting a relative stable oxidative pressure in Q. pubescens under the water stress applied. Moreover, these results suggest a quite good resilience of this species under the most severe climate change scenario in the Mediterranean region.

  6. Modulation of follistatin and myostatin propeptide by anabolic steroids and gender.

    PubMed

    Mosler, S; Geisler, S; Hengevoss, J; Schiffer, T; Piechotta, M; Adler, M; Diel, P

    2013-07-01

    The purpose of this pilot study was to investigate the impact of training, anabolic steroids and endogenous hormones on myostatin-interacting proteins in order to identify manipulations of myostatin signalling. To identify whether analysis of the myostatin interacting proteins follistatin and myostatin propeptide is suitable to detect the abuse of anabolic steroids, their serum concentrations were monitored in untrained males, bodybuilders using anabolic steroids and natural bodybuilders. In addition, we analysed follistatin and myostatin propeptide serum proteins in females during menstrual cycle. Our results showed increased follistatin concentrations in response to anabolic steroids. Furthermore, variations of sex steroid levels during the menstrual cycle had no impact on the expression of follistatin and myostatin propetide. In addition, we identified gender differences in the basal expression of the investigated proteins. In general, follistatin and myostatin propeptide concentrations were relatively stable within the same individual both in males and females. In conclusion, the current findings provide an insight into gender differences in myostatin-interacting proteins and their regulation in response to anabolic steroids and endogenous hormones. Therefore our data provide new aspects for the development of doping prevention strategies.

  7. [Cardiovascular side effects of anabolic-androgenic steroids].

    PubMed

    Kindermann, Wilfried

    2006-09-01

    The intake of anabolic-androgenic steroids (AAS) leads to an increase in skeletal muscle mass and is prohibited as a doping measure in sport. AAS abuse is not limited to competitive athletes. It is also prevalent in subjects who do body building or resistance training for cosmetic reasons only. Out of the numerous and partly serious side effects, the cardiovascular ones are presented here. An increase in left ventricular muscle mass is well documented, and some researchers have even reported concentric hypertrophy. By contrast, resistance training without AAS intake does not lead to increased ventricular wall thickness. AAS do not affect the systolic function of the left ventricle, whereas diastolic function might be impaired. Different ultrastructural myocardial alterations have been documented in animal studies. In addition, AAS can induce arterial hypertension. Blood clotting and fibrinolysis are negatively affected, and several case studies of thrombi exist in young strength athletes. Changes in the concentration of blood lipoproteins, particularly a reduction in vessel-protective HDL cholesterol, can lead to early atherosclerosis. Many case reports exist about cardiac deaths in seemingly healthy subjects-most often body builders and other strength athletes. In fatal and nonfatal myocardial infarctions patent coronary arteries were proven frequently. Besides the prothrombotic effects of AAS, an impaired endothelial function and vasospasms are discussed hypothetically as pathomechanisms. Also, cardiomyopathies can occur due to AAS abuse. On the basis of the described possible cardiovascular side effects, it can be concluded that in cases of sudden cardiac deaths in young athletes, a misuse of AS should be excluded.

  8. Impact of anabolic androgenic steroids on adolescent males.

    PubMed

    Lumia, Augustus R; McGinnis, Marilyn Y

    2010-06-01

    Anabolic androgenic steroid (AAS) use increased dramatically among adolescent males. This review focuses on studies using animal models of AAS exposure during adolescence which is a hormonally sensitive developmental period. AAS exposure during this critical period has wide-ranging consequences, including increased dendritic spine density, altered brain serotonin levels and escalated aggression in response to physical provocation. Human data suggest that AAS induces indiscriminate and unprovoked aggression often described as "'roid rage". However, animal studies indicate that the behavioral impact of AAS is modulated by experiential and social contingencies, a perceived provocation, and the chemical composition of the AAS. The AAS, testosterone increases aggression in juvenile and adult male rats when physically provoked. In contrast, stanzolol, inhibits aggression in both juvenile and adult male rats, even when physically provoked. Nandrolone has minimal effects on aggression, unless preceded by attack training. Exposure to AAS during adolescence may have a host of unintended bio-behavioral consequences. Yet, the perception of harmlessness surrounds AAS use. The perception of harmlessness is promoted by the availability of AAS especially through internet pharmacies. The perception of acceptability is reflected in current cultural ethics that no longer condemn cheating to obtain personal achievement or success. A prevailing conviction is that although AAS are illegal they are not really bad. Reduction of the availability of AAS to adolescents requires ardent legislative and legal intervention. The problem of acceptability can be addressed by educating adolescents about the short-term and long-term effects of AAS on brain and behavior, to increase awareness of the potential consequences of AAS use that apply directly to them.

  9. Paradigm of Professional Integration for Disabled People in Fundació Integralia Vallès: Key Success Factors.

    PubMed

    Gil, Ma Emilia; De Oña, Javier; Picola, Esteve

    2016-01-01

    Fundació Integralia Vallès is a pioneer contact center in Europe that has involved the creation of a healthcare reference center managed exclusively by people with disabilities and degenerative diseases to enable their professional development and ultimately integration into the labour market. The environment created under this project enables effective training and building of skills, capacity and work experience as well as promoting social responsibility among a population group that is at risk of exclusion. The major differentiating factor in Fundació Integralia Vallés is the quality of service provided by its staff, who are particularly sensitive to the issues of health, and who provide professional and human dimension in every attention.

  10. A major latex-like protein is a key factor in crop contamination by persistent organic pollutants.

    PubMed

    Inui, Hideyuki; Sawada, Mami; Goto, Junya; Yamazaki, Kiyoshi; Kodama, Noriko; Tsuruta, Hiroki; Eun, Heesoo

    2013-04-01

    This is the first report, to our knowledge, to reveal important factors by which members of the Cucurbitaceae family, such as cucumber (Cucumis sativus), watermelon (Citrullus lanatus), melon (Cucumis melo), pumpkin (Cucurbita pepo), squash (C. pepo), and zucchini (C. pepo), are selectively polluted with highly toxic hydrophobic contaminants, including organochlorine insecticides and dioxins. Xylem sap of C. pepo ssp. pepo, which is a high accumulator of hydrophobic compounds, solubilized the hydrophobic compound pyrene into the aqueous phase via some protein(s). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of xylem sap of two C. pepo subspecies revealed that the amount of 17-kD proteins in C. pepo ssp. pepo was larger than that in C. pepo ssp. ovifera, a low accumulator, suggesting that these proteins may be related to the translocation of hydrophobic compounds. The protein bands at 17 kD contained major latex-like proteins (MLPs), and the corresponding genes MLP-PG1, MLP-GR1, and MLP-GR3 were cloned from the C. pepo cultivars Patty Green and Gold Rush. Expression of the MLP-GR3 gene in C. pepo cultivars was positively correlated with the band intensity of 17-kD proteins and bioconcentration factors toward dioxins and dioxin-like compounds. Recombinant MLP-GR3 bound polychlorinated biphenyls immobilized on magnetic beads, whereas recombinant MLP-PG1 and MLP-GR1 did not. These results indicate that the high expression of MLP-GR3 in C. pepo ssp. pepo plants and the existence of MLP-GR3 in their xylem sap are related to the efficient translocation of hydrophobic contaminants. These findings should be useful for decreasing the contamination of fruit of the Cucurbitaceae family as well as the phytoremediation of hydrophobic contaminants.

  11. Soil pH and electrical conductivity are key edaphic factors shaping bacterial communities of greenhouse soils in Korea.

    PubMed

    Kim, Jeong Myeong; Roh, An-Sung; Choi, Seung-Chul; Kim, Eun-Jeong; Choi, Moon-Tae; Ahn, Byung-Koo; Kim, Sun-Kuk; Lee, Young-Han; Joa, Jae-Ho; Kang, Seong-Soo; Lee, Shin Ae; Ahn, Jae-Hyung; Song, Jaekyeong; Weon, Hang-Yeon

    2016-12-01

    Soil microorganisms play an essential role in soil ecosystem processes such as organic matter decomposition, nutrient cycling, and plant nutrient availability. The land use for greenhouse cultivation has been increasing continuously, which involves an intensive input of agricultural materials to enhance productivity; however, relatively little is known about bacterial communities in greenhouse soils. To assess the effects of environmental factors on the soil bacterial diversity and community composition, a total of 187 greenhouse soil samples collected across Korea were subjected to bacterial 16S rRNA gene pyrosequencing analysis. A total of 11,865 operational taxonomic units at a 97% similarity cutoff level were detected from 847,560 sequences. Among nine soil factors evaluated; pH, electrical conductivity (EC), exchangeable cations (Ca(2+), Mg(2+), Na(+), and K(+)), available P2O5, organic matter, and NO3-N, soil pH was most strongly correlated with bacterial richness (polynomial regression, pH: R(2) = 0.1683, P < 0.001) and diversity (pH: R(2) = 0.1765, P < 0.001). Community dissimilarities (Bray-Curtis distance) were positively correlated with Euclidean distance for pH and EC (Mantel test, pH: r = 0.2672, P < 0.001; EC: r = 0.1473, P < 0.001). Among dominant phyla (> 1%), the relative abundances of Proteobacteria, Gemmatimonadetes, Acidobacteria, Bacteroidetes, Chloroflexi, and Planctomycetes were also more strongly correlated with pH and EC values, compared with other soil cation contents, such as Ca(2+), Mg(2+), Na(+), and K(+). Our results suggest that, despite the heterogeneity of various environmental variables, the bacterial communities of the intensively cultivated greenhouse soils were particularly influenced by soil pH and EC. These findings therefore shed light on the soil microbial ecology of greenhouse cultivation, which should be helpful for devising effective management strategies to enhance soil microbial diversity and improving crop productivity.

  12. Replication and extension of a hierarchical model of social anxiety and depression: fear of positive evaluation as a key unique factor in social anxiety.

    PubMed

    Weeks, Justin W

    2015-01-01

    Wang, Hsu, Chiu, and Liang (2012, Journal of Anxiety Disorders, 26, 215-224) recently proposed a hierarchical model of social interaction anxiety and depression to account for both the commonalities and distinctions between these conditions. In the present paper, this model was extended to more broadly encompass the symptoms of social anxiety disorder, and replicated in a large unselected, undergraduate sample (n = 585). Structural equation modeling (SEM) and hierarchical regression analyses were employed. Negative affect and positive affect were conceptualized as general factors shared by social anxiety and depression; fear of negative evaluation (FNE) and disqualification of positive social outcomes were operationalized as specific factors, and fear of positive evaluation (FPE) was operationalized as a factor unique to social anxiety. This extended hierarchical model explicates structural relationships among these factors, in which the higher-level, general factors (i.e., high negative affect and low positive affect) represent vulnerability markers of both social anxiety and depression, and the lower-level factors (i.e., FNE, disqualification of positive social outcomes, and FPE) are the dimensions of specific cognitive features. Results from SEM and hierarchical regression analyses converged in support of the extended model. FPE is further supported as a key symptom that differentiates social anxiety from depression.

  13. Effects of Solvent and Ion Source Pressure on the Analysis of Anabolic Steroids by Low Pressure Photoionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Liu, Chengyuan; Zhu, Yanan; Yang, Jiuzhong; Zhao, Wan; Lu, Deen; Pan, Yang

    2017-01-01

    Solvent and ion source pressure were two important factors relating to the photon induced ion-molecule reactions in low pressure photoionization (LPPI). In this work, four anabolic steroids were analyzed by LPPI mass spectrometry. Both the ion species present and their relative abundances could be controlled by switching the solvent and adjusting the ion source pressure. Whereas M•+, MH+, [M - H2O]+, and solvent adducts were observed in positive LPPI, [M - H]- and various oxidation products were abundant in negative LPPI. Changing the solvent greatly affected formation of the ion species in both positive and negative ion modes. The ion intensities of the solvent adduct and oxygen adduct were selectively enhanced when the ion source pressure was elevated from 68 to 800 Pa. The limit of detection could be decreased by increasing the ion source pressure.

  14. Key Survival Factor, Mcl-1, Correlates with Sensitivity to Combined Bcl-2/Bcl-xL Blockade.

    PubMed

    Williams, Michelle M; Lee, Linus; Hicks, Donna J; Joly, Meghan M; Elion, David; Rahman, Bushra; McKernan, Courtney; Sanchez, Violeta; Balko, Justin M; Stricker, Thomas; Estrada, Monica Valeria; Cook, Rebecca S

    2017-03-01

    An estimated 40,000 deaths will be attributed to breast cancer in 2016, underscoring the need for improved therapies. Evading cell death is a major hallmark of cancer, driving tumor progression and therapeutic resistance. To evade apoptosis, cancers use antiapoptotic Bcl-2 proteins to bind to and neutralize apoptotic activators, such as Bim. Investigation of antiapoptotic Bcl-2 family members in clinical breast cancer datasets revealed greater expression and more frequent gene amplification of MCL1 as compared with BCL2 or BCL2L1 (Bcl-xL) across three major molecular breast cancer subtypes, Luminal (A and B), HER2-enriched, and Basal-like. While Mcl-1 protein expression was elevated in estrogen receptor α (ERα)-positive and ERα-negative tumors as compared with normal breast, Mcl-1 staining was higher in ERα(+) tumors. Targeted Mcl-1 blockade using RNAi increased caspase-mediated cell death in ERα(+) breast cancer cells, resulting in sustained growth inhibition. In contrast, combined blockade of Bcl-2 and Bcl-xL only transiently induced apoptosis, as cells rapidly acclimated through Mcl-1 upregulation and enhanced Mcl-1 activity, as measured in situ using Mcl-1/Bim proximity ligation assays. Importantly, MCL1 gene expression levels correlated inversely with sensitivity to pharmacologic Bcl-2/Bcl-xL inhibition in luminal breast cancer cells, whereas no relationship was seen between the gene expression of BCL2 or BCL2L1 and sensitivity to Bcl-2/Bcl-xL inhibition. These results demonstrate that breast cancers rapidly deploy Mcl-1 to promote cell survival, particularly when challenged with blockade of other Bcl-2 family members, warranting the continued development of Mcl-1-selective inhibitors for targeted tumor cell killing.Implications: Mcl-1 levels predict breast cancer response to inhibitors targeting other Bcl-2 family members, and demonstrate the key role played by Mcl-1 in resistance to this drug class. Mol Cancer Res; 15(3); 259-68. ©2016 AACR.

  15. Anabolic Steroid Use: Federal Efforts to Prevent and Reduce Anabolic Steroid Abuse among Teenagers. Report to the Committee on Oversight and Government Reform, House of Representatives. GAO-08-15

    ERIC Educational Resources Information Center

    Government Accountability Office, 2007

    2007-01-01

    The abuse of anabolic steroids by teenagers--that is, their use without a prescription--is a health concern. Anabolic steroids are synthetic forms of the hormone testosterone that can be taken orally, injected, or rubbed on the skin. Although a 2006 survey funded by the National Institute on Drug Abuse (NIDA) found that less than 3 percent of 12th…

  16. Plant Actin-Depolymerizing Factors Possess Opposing Biochemical Properties Arising from Key Amino Acid Changes throughout Evolution.

    PubMed

    Nan, Qiong; Qian, Dong; Niu, Yue; He, Yongxing; Tong, Shaofei; Niu, Zhimin; Ma, Jianchao; Yang, Yang; An, Lizhe; Wan, Dongshi; Xiang, Yun

    2017-02-01

    Functional divergence in paralogs is an important genetic source of evolutionary innovation. Actin-depolymerizing factors (ADFs) are among the most important actin binding proteins and are involved in generating and remodeling actin cytoskeletal architecture via their conserved F-actin severing or depolymerizing activity. In plants, ADFs coevolved with actin, but their biochemical properties are diverse. Unfortunately, the biochemical function of most plant ADFs and the potential mechanisms of their functional divergence remain unclear. Here, in vitro biochemical analyses demonstrated that all 11 ADF genes in Arabidopsis thaliana exhibit opposing biochemical properties. Subclass III ADFs evolved F-actin bundling (B-type) function from conserved F-actin depolymerizing (D-type) function, and subclass I ADFs have enhanced D-type function. By tracking historical mutation sites on ancestral proteins, several fundamental amino acid residues affecting the biochemical functions of these proteins were identified in Arabidopsis and various plants, suggesting that the biochemical divergence of ADFs has been conserved during the evolution of angiosperm plants. Importantly, N-terminal extensions on subclass III ADFs that arose from intron-sliding events are indispensable for the alteration of D-type to B-type function. We conclude that the evolution of these N-terminal extensions and several conserved mutations produced the diverse biochemical functions of plant ADFs from a putative ancestor.

  17. Plant Actin-Depolymerizing Factors Possess Opposing Biochemical Properties Arising from Key Amino Acid Changes throughout Evolution[OPEN

    PubMed Central

    Nan, Qiong; Niu, Yue; He, Yongxing; Tong, Shaofei; Niu, Zhimin; Ma, Jianchao; Yang, Yang; An, Lizhe; Wan, Dongshi

    2017-01-01

    Functional divergence in paralogs is an important genetic source of evolutionary innovation. Actin-depolymerizing factors (ADFs) are among the most important actin binding proteins and are involved in generating and remodeling actin cytoskeletal architecture via their conserved F-actin severing or depolymerizing activity. In plants, ADFs coevolved with actin, but their biochemical properties are diverse. Unfortunately, the biochemical function of most plant ADFs and the potential mechanisms of their functional divergence remain unclear. Here, in vitro biochemical analyses demonstrated that all 11 ADF genes in Arabidopsis thaliana exhibit opposing biochemical properties. Subclass III ADFs evolved F-actin bundling (B-type) function from conserved F-actin depolymerizing (D-type) function, and subclass I ADFs have enhanced D-type function. By tracking historical mutation sites on ancestral proteins, several fundamental amino acid residues affecting the biochemical functions of these proteins were identified in Arabidopsis and various plants, suggesting that the biochemical divergence of ADFs has been conserved during the evolution of angiosperm plants. Importantly, N-terminal extensions on subclass III ADFs that arose from intron-sliding events are indispensable for the alteration of D-type to B-type function. We conclude that the evolution of these N-terminal extensions and several conserved mutations produced the diverse biochemical functions of plant ADFs from a putative ancestor. PMID:28123105

  18. Identification and dissection of a key enhancer mediating cranial neural crest specific expression of transcription factor, Ets-1.

    PubMed

    Barembaum, Meyer; Bronner, Marianne E

    2013-10-15

    Neural crest cells form diverse derivatives that vary according to their level of origin along the body axis, with only cranial neural crest cells contributing to facial skeleton. Interestingly, the transcription factor Ets-1 is uniquely expressed in cranial but not trunk neural crest, where it functions as a direct input into neural crest specifier genes, Sox10 and FoxD3. We have isolated and interrogated a cis-regulatory element, conserved between birds and mammals, that drives reporter expression in a manner that recapitulates that of endogenous Ets-1 expression in the neural crest. Within a minimal Ets-1 enhancer region, mutation of putative binding sites for SoxE, homeobox, Ets, TFAP2 or Fox proteins results in loss or reduction of neural crest enhancer activity. Morpholino-mediated loss-of-function experiments show that Sox9, Pax7, Msx1/2, Ets-1, TFAP2A and FoxD3, all are required for enhancer activity. In contrast, mutation of a putative cMyc/E-box sequence augments reporter expression, consistent with this being a repressor binding site. Taken together, these results uncover new inputs into Ets-1, revealing critical links in the cranial neural crest gene regulatory network.

  19. Transcriptome analysis of sexually dimorphic Chinese white wax scale insects reveals key differences in developmental programs and transcription factor expression.

    PubMed

    Yang, Pu; Chen, Xiao-Ming; Liu, Wei-Wei; Feng, Ying; Sun, Tao

    2015-01-30

    The Chinese white wax scale insect, Ericerus pela, represents one of the most dramatic examples of sexual dimorphism in any insect species. In this study, we showed that although E. pela males display complete metamorphosis similar to holometabolous insects, the species forms the sister group to Acyrthosiphon pisum and cluster with hemimetabolous insects. The gene expression profile and Gene Ontology (GO) analyses revealed that the two sexes engaged in distinct developmental programs. In particular, female development appeared to prioritize the expression of genes related to cellular, metabolic, and developmental processes and to anatomical structure formation in nymphs. By contrast, male nymphal development is characterized by the significant down-regulation of genes involved in chitin, the respiratory system, and neurons. The wing and appendage morphogenesis, anatomical and tissue structure morphogenesis programs activated after male nymphal development. Transcription factors (that convey juvenile hormone or ecdysone signals, and Hox genes) and DNA methyltransferase were also differentially expressed between females and males. These results may indicate the roles that these differentially expressed genes play in regulating sexual dimorphism through orchestrating complex genetic programs. This differential expression was particularly prominent for processes linked to female development and wing development in males.

  20. Searching for a Role of Nursing Personnel in Developing Landscape of Ehealth: Factors Determining Attitudes toward Key Patient Empowering Applications

    PubMed Central

    Duplaga, Mariusz

    2016-01-01

    Introduction Nurses may play an important role in the delivery of medical services based on the use of ehealth tools. Nevertheless, their taking an active role in an ehealth environment depends on their possessing the appropriate skills and mindset. The main objective of this paper was to assess nurses’ opinions and to analyze the predictors of their acceptance of ehealth features relevant to patient empowerment with a strong focus on chronic care. Methods A survey was conducted among nurses from hospital centers of south-eastern Poland based on a questionnaire designed to assess their attitudes toward the ehealth domain. The predictors of the nurses’ acceptance of ehealth usage within specific contexts were assessed with uni- and multivariate logistic regression. Results An analysis was performed on data from 648 questionnaires retained after a quality check. The duration of Internet use was consistently related to higher acceptance of ehealth applications and more certainty regarding the reliability of health-related information available on the Internet. Nurses from urban medical centers were more skeptical about the use of specific ehealth solutions. Conclusion Previous experience in using information technologies is the main factor influencing the acceptance of specific ehealth solutions relevant for care provided to patients suffering from chronic conditions. PMID:27049525

  1. Transcriptome Analysis of Sexually Dimorphic Chinese White Wax Scale Insects Reveals Key Differences in Developmental Programs and Transcription Factor Expression

    PubMed Central

    Yang, Pu; Chen, Xiao-Ming; Liu, Wei-Wei; Feng, Ying; Sun, Tao

    2015-01-01

    The Chinese white wax scale insect, Ericerus pela, represents one of the most dramatic examples of sexual dimorphism in any insect species. In this study, we showed that although E. pela males display complete metamorphosis similar to holometabolous insects, the species forms the sister group to Acyrthosiphon pisum and cluster with hemimetabolous insects. The gene expression profile and Gene Ontology (GO) analyses revealed that the two sexes engaged in distinct developmental programs. In particular, female development appeared to prioritize the expression of genes related to cellular, metabolic, and developmental processes and to anatomical structure formation in nymphs. By contrast, male nymphal development is characterized by the significant down-regulation of genes involved in chitin, the respiratory system, and neurons. The wing and appendage morphogenesis, anatomical and tissue structure morphogenesis programs activated after male nymphal development. Transcription factors (that convey juvenile hormone or ecdysone signals, and Hox genes) and DNA methyltransferase were also differentially expressed between females and males. These results may indicate the roles that these differentially expressed genes play in regulating sexual dimorphism through orchestrating complex genetic programs. This differential expression was particularly prominent for processes linked to female development and wing development in males. PMID:25634031

  2. A naturally occurring naringenin derivative exerts potent bone anabolic effects by mimicking oestrogen action on osteoblasts

    PubMed Central

    Swarnkar, Gaurav; Sharan, Kunal; Siddiqui, Jawed A; Mishra, Jay Sharan; Khan, Kainat; Khan, Mohd Parvez; Gupta, Varsha; Rawat, Preeti; Maurya, Rakesh; Dwivedi, Anil K; Sanyal, Sabyasachi; Chattopadhyay, Naibedya

    2012-01-01

    BACKGROUND AND PURPOSE Naringenin and its derivatives have been assessed in bone health for their oestrogen-‘like’ effects but low bioavailability impedes clinical potential. This study was aimed at finding a potent form of naringenin with osteogenic action. EXPERIMENTAL APPROACH Osteoblast cultures were harvested from mouse calvaria to study differentiation by naringenin, isosakuranetin, poncirin, phloretin and naringenin-6-C-glucoside (NCG). Balb/cByJ ovariectomized (OVx) mice without or with osteopenia were given naringenin, NCG, 17β-oestradiol (E2) or parathyroid hormone (PTH). Efficacy was evaluated by bone microarchitecture using microcomputed tomography and determination of new bone formation by fluorescent labelling of bone. Plasma levels of NCG and naringenin were determined by HPLC. KEY RESULTS NCG stimulated osteoblast differentiation more potently than naringenin, while isosakuranetin, poncirin or phloretin had no effect. NCG had better oral bioavailability than naringenin. NCG increased the mRNA levels of oestrogen receptors (ERs) and bone morphogenetic protein (an ER responsive gene) in vivo, more than naringenin. In OVx mice, NCG treatment in a preventive protocol increased bone formation rate (BFR) and improved trabecular microarchitecture more than naringenin or E2. In osteopenic mice, NCG but not naringenin, in a therapeutic protocol, increased BFR and improved trabecular microarchitecture, comparable with effects of PTH treatment. Stimulatory effects of NCG on osteoblasts were abolished by an ER antagonist. NCG transactivated ERβ but not ERα. NCG exhibited no uterine oestrogenicity unlike naringenin. CONCLUSIONS AND IMPLICATIONS NCG is a potent derivative of naringenin that has bone anabolic action through the activation of osteoblast ERs and exhibited substantial oral bioavailability. PMID:21864313

  3. Chilling stress--the key predisposing factor for causing Alternaria alternata infection and leading to cotton (Gossypium hirsutum L.) leaf senescence.

    PubMed

    Zhao, Jingqing; Li, Sha; Jiang, Tengfei; Liu, Zhi; Zhang, Wenwei; Jian, Guiliang; Qi, Fangjun

    2012-01-01

    Leaf senescence plays a vital role in nutrient recycling and overall capacity to assimilate carbon dioxide. Cotton premature leaf senescence, often accompanied with unexpected short-term low temperature, has been occurring with an increasing frequency in many cotton-growing areas and causes serious reduction in yield and quality of cotton. The key factors for causing and promoting cotton premature leaf senescence are still unclear. In this case, the relationship between the pre-chilling stress and Alternaria alternata infection for causing cotton leaf senescence was investigated under precisely controlled laboratory conditions with four to five leaves stage cotton plants. The results showed short-term chilling stress could cause a certain degree of physiological impairment to cotton leaves, which could be recovered to normal levels in 2-4 days when the chilling stresses were removed. When these chilling stress injured leaves were further inoculated with A. alternata, the pronounced appearance and development of leaf spot disease, and eventually the pronounced symptoms of leaf senescence, occurred on these cotton leaves. The onset of cotton leaf senescence at this condition was also reflected in various physiological indexes such as irreversible increase in malondialdehyde (MDA) content and electrolyte leakage, irreversible decrease in soluble protein content and chlorophyll content, and irreversible damage in leaves' photosynthesis ability. The presented results demonstrated that chilling stress acted as the key predisposing factor for causing A. alternata infection and leading to cotton leaf senescence. It could be expected that the understanding of the key factors causing and promoting cotton leaf senescence would be helpful for taking appropriate management steps to prevent cotton premature leaf senescence.

  4. Clenbuterol and anabolic steroids: a previously unreported cause of myocardial infarction with normal coronary arteriograms.

    PubMed

    Goldstein, D R; Dobbs, T; Krull, B; Plumb, V J

    1998-08-01

    During the last 10 years, several cases of myocardial infarction associated with anabolic steroid use have been reported. Postulated mechanisms to explain this association have included changes in lipid levels, the fibrinolytic system, and platelet aggregation. Clenbuterol is a beta 2-agonist with anabolic properties that has not been seen previously with myocardial infarction. We report a case of myocardial infarction in an otherwise healthy 26-year-old body-builder who recently used clenbuterol and anabolic steroids. In this case, synergistic effects of the two agents seem likely to have played a role in the infarct. The normal coronary arteriograms before any anticoagulant or thrombolytic therapy strongly suggest coronary spasm as the mechanism of the infarct.

  5. Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder

    PubMed Central

    Bispo, Miguel; Valente, Ana; Maldonado, Rosário; Palma, Rui; Glória, Helena; Nóbrega, João; Alexandrino, Paula

    2009-01-01

    Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure. PMID:19533818

  6. Doping control analysis of anabolic steroids in equine urine by gas chromatography-tandem mass spectrometry.

    PubMed

    Wong, April S Y; Leung, Gary N W; Leung, David K K; Wan, Terence S M

    2016-09-08

    Anabolic steroids are banned substances in equine sports. Gas chromatography-mass spectrometry (GC-MS) has been the traditional technique for doping control analysis of anabolic steroids in biological samples. Although liquid chromatography-mass spectrometry (LC/MS) has become an important technique in doping control, the detection of saturated hydroxysteroids by LC-MS remains a problem due to their low ionization efficiency under electrospray. The recent development in fast-scanning gas-chromatography-triple-quadrupole mass spectrometry (GC-MS/MS) has provided a better alternative with a significant reduction in chemical noise by means of selective reaction monitoring. Herein, we present a sensitive and selective method for the screening of over 50 anabolic steroids in equine urine using gas chromatography-tandem mass spectrometry (GC-MS/MS). Copyright © 2016 John Wiley & Sons, Ltd.

  7. Imitation of phase I oxidative metabolism of anabolic steroids by titanium dioxide photocatalysis.

    PubMed

    Ruokolainen, Miina; Valkonen, Minna; Sikanen, Tiina; Kotiaho, Tapio; Kostiainen, Risto

    2014-12-18

    The aim of this study was to investigate the feasibility of titanium dioxide (TiO2) photocatalysis for oxidation of anabolic steroids and for imitation of their phase I metabolism. The photocatalytic reaction products of five anabolic steroids were compared to their phase I in vitro metabolites produced by human liver microsomes (HLM). The same main reaction types - hydroxylation, dehydrogenation and combination of these two - were observed both in TiO2 photocatalysis and in microsomal incubations. Several isomers of each product type were formed in both systems. Based on the same mass, retention time and similarity of the product ion spectra, many of the products observed in HLM reactions were also formed in TiO2 photocatalytic reactions. However, products characteristic to only either one of the systems were also formed. In conclusion, TiO2 photocatalysis is a rapid, simple and inexpensive method for imitation of phase I metabolism of anabolic steroids and production of metabolite standards.

  8. Statistical study to identify the key factors governing ground water recharge in the watersheds of the arid Central Asia.

    PubMed

    Zhu, Binq-Qi; Wang, Yue-Ling

    2016-01-01

    Understanding the source and recharge of ground waters is of great significance to our knowledge in hydrological cycles in arid environments over the world. Northern Xinjiang in northwestern China is a significant repository of information relating to the hydrological evolution and climatic changes in central Asia. In this study, two multivariate statistical techniques, hierarchical cluster analysis (HCA) and principal component analysis (PCA), were used to assess the ground water recharge and its governing factors, with the principal idea of exploring the above techniques to utilize all available hydrogeochemical variables in the quality assessment, which are not considered in the conventional techniques like Stiff and Piper diagrams. Q-mode HCA and R-mode PCA were combined to partition the water samples into seven major water clusters (C1-C7) and three principal components (PC1-PC3, PC1 salinity, PC2 hydroclimate, PC3 contaminant). The water samples C1 + C4 were classified as recharge area waters (Ca-HCO3 water), C2 + C3 as transitional zone waters (Ca-Mg-HCO3-SO4 water), and C5 + C6 + C7 as discharge area waters (Na-SO4 water). Based on the Q-mode PCA scores, three groups of geochemical processes influencing recharge regimes were identified: geogenic (i.e., caused by natural geochemical processes), geomorphoclimatic (caused by topography and climate), and anthropogenic (caused by ground water contamination). It is proposed that differences in recharge mechanism and ground water evolution, and possible bedrock composition difference, are responsible for the chemical genesis of these waters. These will continue to influence the geochemistry of the northern Xinjiang drainage system for a long time due to its steady tectonics and arid climate. This study proved that the chemistry differentiation of ground water can effectively support the identification of ground water recharge and evolution patterns.

  9. The Cytosolic pH of Individual Saccharomyces cerevisiae Cells Is a Key Factor in Acetic Acid Tolerance.

    PubMed

    Fernández-Niño, Miguel; Marquina, Maribel; Swinnen, Steve; Rodríguez-Porrata, Boris; Nevoigt, Elke; Ariño, Joaquín

    2015-11-01

    It was shown recently that individual cells of an isogenic Saccharomyces cerevisiae population show variability in acetic acid tolerance, and this variability affects the quantitative manifestation of the trait at the population level. In the current study, we investigated whether cell-to-cell variability in acetic acid tolerance could be explained by the observed differences in the cytosolic pHs of individual cells immediately before exposure to the acid. Results obtained with cells of the strain CEN.PK113-7D in synthetic medium containing 96 mM acetic acid (pH 4.5) showed a direct correlation between the initial cytosolic pH and the cytosolic pH drop after exposure to the acid. Moreover, only cells with a low initial cytosolic pH, which experienced a less severe drop in cytosolic pH, were able to proliferate. A similar correlation between initial cytosolic pH and cytosolic pH drop was also observed in the more acid-tolerant strain MUCL 11987-9. Interestingly, a fraction of cells in the MUCL 11987-9 population showed initial cytosolic pH values below the minimal cytosolic pH detected in cells of the strain CEN.PK113-7D; consequently, these cells experienced less severe drops in cytosolic pH. Although this might explain in part the difference between the two strains with regard to the number of cells that resumed proliferation, it was observed that all cells from strain MUCL 11987-9 were able to proliferate, independently of their initial cytosolic pH. Therefore, other factors must also be involved in the greater ability of MUCL 11987-9 cells to endure strong drops in cytosolic pH.

  10. Growing Season Length as a Key Factor of Cumulative Net Ecosystem Exchange Over the Pine Forest Ecosystems in Europe

    NASA Astrophysics Data System (ADS)

    Danielewska, Alina; Urbaniak, Marek; Olejnik, Janusz

    2015-04-01

    The Scots pine is one of the most important species in European and Asian forests. Due to a widespread occurrence of pine forests, their significance in the energy and mass exchange between the Earth surface and the atmosphere is also important, particularly in the context of climate change and greenhouse gases balance. The aim of this work is to present the relationship between the average annual net ecosystem productivity and growing season length, latitude and air temperature (tay) over Europe. Therefore, CO2 flux measurement data from eight European pine dominated forests were used. The observations suggest that there is a correlation between the intensity of CO2 uptake or emission by a forest stand and the above mentioned parameters. Based on the obtained results, all of the selected pine forest stands were CO2 sinks, except a site in northern Finland. The carbon dioxide uptake increased proportionally with the increase of growing season length (9.212 g C m-2 y-1 per day of growing season, R2 = 0.53, p = 0.0399). This dependency showed stronger correlation and higher statistical significance than both relationships between annual net ecosystem productivity and air temperature (R2 = 0.39, p = 0.096) and annual net ecosystem productivity and latitude (R2 = 0.47, p = 0.058). The CO2 emission surpassed assimilation in winter, early spring and late autumn. Moreover, the appearance of late, cold spring and early winter, reduced annual net ecosystem productivity. Therefore, the growing season length can be considered as one of the main factor affecting the annual carbon budget of pine forests.

  11. Nitrous oxide emissions from intensive agricultural systems: Variations between crops and seasons, key driving variables, and mean emission factors

    NASA Astrophysics Data System (ADS)

    Dobbie, K. E.; McTaggart, I. P.; Smith, K. A.

    1999-11-01

    Emissions of nitrous oxide from intensively managed agricultural fields were measured over 3 years. Exponential increases in flux occurred with increasing soil water- filled pore space (WFPS) and temperature; increases in soil mineral N content due to fertilizer application also stimulated emissions. Fluxes were low when any of these variables was below a critical value. The largest fluxes occurred when WFPS values were very high (70-90%), indicating that denitrification was the major process responsible. The relationships with the driving variables showed strong similarities to those reported for very different environments: irrigated sugar cane crops, pastures, and forest in the tropics. Annual emissions varied widely (0.3-18.4 kg N2O-N ha-1). These variations were principally due to the degree of coincidence of fertilizer application and major rainfall events. It is concluded therefore that several years' data are required from any agricultural ecosystem in a variable climate to obtain a robust estimate of mean N2O fluxes. The emissions from small-grain cereals (winter wheat and spring barley) were consistently lower (0.2-0.7 kg N2O-N per 100 kg N applied) than from cut grassland (0.3-5.8 kg N2O- N per 100 kg N). Crops such as broccoli and potatoes gave emissions of the same order as those from the grassland. Although these differences between crop types are not apparent in general data comparisons, there may well be distinct regional differences in the relative and absolute emissions from different crops, due to local factors relating to soil type, weather patterns, and agricultural management practices. This will only be determined by more detailed comparative studies.

  12. Vascular endothelial growth factor-D is a key molecule that enhances lymphatic metastasis of soft tissue sarcomas

    SciTech Connect

    Yanagawa, Takashi; Shinozaki, Tetsuya; Watanabe, Hideomi; Saito, Kenichi; Raz, Avraham; Takagishi, Kenji

    2012-04-15

    Studies on lymph node metastasis of soft tissue sarcomas are insufficient because of its rarity. In this study, we examined the expressions of vascular endothelial growth factor (VEGF)-C and VEGF-D in soft tissue sarcomas metastasized to lymph nodes. In addition, the effects of the two molecules on the barrier function of a lymphatic endothelial cell monolayer against sarcoma cells were analyzed. We examined 7 patients who had soft tissue sarcomas with lymph node metastases and who had undergone neither chemotherapy nor radiotherapy before lymphadenectomy. Immunohistochemistry revealed that 2 of 7 sarcomas that metastasized to lymph nodes expressed VEGF-C both in primary and metastatic lesions. On the other hand, VEGF-D expression was detected in 4 of 7 primary and 7 of 7 metastatic lesions, respectively. Interestingly, 3 cases that showed no VEGF-D expression at primary sites expressed VEGF-D in metastatic lesions. Recombinant VEGF-C at 10{sup -8} and VEGF-D at 10{sup -7}and 10{sup -8} g/ml significantly increased the random motility of lymphatic endothelial cells compared with controls. VEGF-D significantly increased the migration of sarcoma cells through lymphatic endothelial monolayers. The fact that VEGF-D induced the migration of fibrosarcomas through the lymphatic endothelial monolayer is the probable reason for the strong relationship between VEGF-D expression and lymph node metastasis in soft tissue sarcomas. The important propensities of this molecule for the increase of lymph node metastases are not only lymphangiogenesis but also down-regulation of the barrier function of lymphatic endothelial monolayers, which facilitates sarcoma cells entering the lymphatic circulation.

  13. Topography and crop management are key factors for the development of american leaf spot epidemics on coffee in costa rica.

    PubMed

    Avelino, Jacques; Cabut, Sandrine; Barboza, Bernardo; Barquero, Miguel; Alfaro, Ronny; Esquivel, César; Durand, Jean-François; Cilas, Christian

    2007-12-01

    ABSTRACT We monitored the development of American leaf spot of coffee, a disease caused by the gemmiferous fungus Mycena citricolor, in 57 plots in Costa Rica for 1 or 2 years in order to gain a clearer understanding of conditions conducive to the disease and improve its control. During the investigation, characteristics of the coffee trees, crop management, and the environment were recorded. For the analyses, we used partial least-squares regression via the spline functions (PLSS), which is a nonlinear extension to partial least-squares regression (PLS). The fungus developed well in areas located between approximately 1,100 and 1,550 m above sea level. Slopes were conducive to its development, but eastern-facing slopes were less affected than the others, probably because they were more exposed to sunlight, especially in the rainy season. The distance between planting rows, the shade percentage, coffee tree height, the type of shade, and the pruning system explained disease intensity due to their effects on coffee tree shading and, possibly, on the humidity conditions in the plot. Forest trees and fruit trees intercropped with coffee provided particularly propitious conditions. Apparently, fertilization was unfavorable for the disease, probably due to dilution phenomena associated with faster coffee tree growth. Finally, series of wet spells interspersed with dry spells, which were frequent in the middle of the rainy season, were critical for the disease, probably because they affected the production and release of gemmae and their viability. These results could be used to draw up a map of epidemic risks taking topographical factors into account. To reduce those risks and improve chemical control, our results suggested that farmers should space planting rows further apart, maintain light shading in the plantation, and prune their coffee trees.

  14. Identifying key stage-specific genes and transcription factors for gastric cancer based on RNA-sequencing data

    PubMed Central

    Wang, Yan

    2017-01-01

    Abstract Background: To identify gastric cancer (GC)-associated genes and transcription factors (TFs) using RNA-sequencing (RNA-seq) data of Asians. Materials and methods: The RNA-seq data (GSE36968) were downloaded from Gene Expression Omnibus database, including 6 noncancerous gastric tissue samples, 5 stage I GC samples, 5 stage II GC samples, 8 stage III GC samples, and 6 stage IV GC samples. The gene expression values in each sample were calculated using Cuffdiff. Following, stage-specific genes were identified by 1-way analysis of variance and hierarchical clustering analysis. Upstream TFs were identified using Seqpos. Besides, functional enrichment analysis of stage-specific genes was performed by DAVID. In addition, the underlying protein–protein interactions (PPIs) information among stage IV-specific genes were extracted from STRING database and PPI network was constructed using Cytoscape software. Results: A total of 3576 stage-specific genes were identified, including 813 specifically up-regulated genes in the normal gastric tissues, 2224 stage I and II-specific genes, and 539 stage IV-specific genes. Also, a total of 9 and 11 up-regulated TFs were identified for the stage I and II-specific genes and stage IV-specific genes, respectively. Functional enrichment showed SPARC, MMP17, and COL6A3 were related to extracellular matrix. Notably, 2 regulatory pathways HOXA4-GLI3-RUNX2-FGF2 and HMGA2-PRKCA were obtained from the PPI network for stage IV-specific genes. In the PPI network, TFs HOXA4 and HMGA2 might function via mediating other genes. Conclusion: These stage-specific genes and TFs might act in the pathogenesis of GC in Asians. PMID:28121923

  15. DNA Polymerase κ Is a Key Cellular Factor for the Formation of Covalently Closed Circular DNA of Hepatitis B Virus

    PubMed Central

    Qi, Yonghe; Gao, Zhenchao; Peng, Bo; Yan, Huan; Tang, Dingbin; Song, Zilin; He, Wenhui; Sun, Yinyan; Guo, Ju-Tao; Li, Wenhui

    2016-01-01

    Hepatitis B virus (HBV) infection of hepatocytes begins by binding to its cellular receptor sodium taurocholate cotransporting polypeptide (NTCP), followed by the internalization of viral nucleocapsid into the cytoplasm. The viral relaxed circular (rc) DNA genome in nucleocapsid is transported into the nucleus and converted into covalently closed circular (ccc) DNA to serve as a viral persistence reservoir that is refractory to current antiviral therapies. Host DNA repair enzymes have been speculated to catalyze the conversion of rcDNA to cccDNA, however, the DNA polymerase(s) that fills the gap in the plus strand of rcDNA remains to be determined. Here we conducted targeted genetic screening in combination with chemical inhibition to identify the cellular DNA polymerase(s) responsible for cccDNA formation, and exploited recombinant HBV with capsid coding deficiency which infects HepG2-NTCP cells with similar efficiency of wild-type HBV to assure cccDNA synthesis is exclusively from de novo HBV infection. We found that DNA polymerase κ (POLK), a Y-family DNA polymerase with maximum activity in non-dividing cells, substantially contributes to cccDNA formation during de novo HBV infection. Depleting gene expression of POLK in HepG2-NTCP cells by either siRNA knockdown or CRISPR/Cas9 knockout inhibited the conversion of rcDNA into cccDNA, while the diminished cccDNA formation in, and hence the viral infection of, the knockout cells could be effectively rescued by ectopic expression of POLK. These studies revealed that POLK is a crucial host factor required for cccDNA formation during a de novo HBV infection and suggest that POLK may be a potential target for developing antivirals against HBV. PMID:27783675

  16. Stature and jumping height are required in female volleyball, but motor coordination is a key factor for future elite success.

    PubMed

    Pion, Johan A; Fransen, Job; Deprez, Dieter N; Segers, Veerle I; Vaeyens, Roel; Philippaerts, Renaat M; Lenoir, Matthieu

    2015-06-01

    It was hypothesized that differences in anthropometry, physical performance, and motor coordination would be found between Belgian elite and sub-elite level female volleyball players using a retrospective analysis of test results gathered over a 5-year period. The test sample in this study consisted of 21 young female volleyball players (15.3 ± 1.5 years) who were selected to train at the Flemish Top Sports Academy for Volleyball in 2008. All players (elite, n = 13; sub-elite, n = 8) were included in the same talent development program, and the elite-level athletes were of a high to very high performance levels according to European competition level in 2013. Five multivariate analyses of variance were used. There was no significant effect of playing level on measures of anthropometry (F = 0.455, p = 0.718, (Equation is included in full-text article.)= 0.07), flexibility (F = 1.861, p = 0.188, (Equation is included in full-text article.)= 0.19), strength (F = 1.218, p = 0.355, (Equation is included in full-text article.)= 0.32); and speed and agility (F = 1.176, p = 0.350, (Equation is included in full-text article.)= 0.18). Multivariate analyses of variance revealed significant multivariate effects between playing levels for motor coordination (F = 3.470, p = 0.036, (Equation is included in full-text article.)= 0.59). A Mann-Whitney U test and a sequential discriminant analysis confirmed these results. Previous research revealed that stature and jump height are prerequisites for talent identification in female volleyball. In addition, the results show that motor coordination is an important factor in determining inclusion into the elite level in female volleyball.

  17. ‘Tempos’ management in primary care: a key factor for classifying adverse events, and improving quality and safety

    PubMed Central

    Brami, J

    2012-01-01

    Background The role of time management in safe and efficient medicine is important but poorly incorporated into the taxonomies of error in primary care. This paper addresses the lack of time management, presenting a framework integrating five time scales termed ‘Tempos’ requiring parallel processing by GPs: the disease's tempo (unexpected rapid evolutions, slow reaction to treatment); the office's tempo (day-to-day agenda and interruptions); the patient's tempo (time to express symptoms, compliance, emotion); the system's tempo (time for appointments, exams, and feedback); and the time to access to knowledge. The art of medicine is to control all of these tempos in parallel and simultaneously. Method Two qualified physicians reviewed a sample of 1046 malpractice claims from one liability insurer to determine whether a medical injury had occurred and, if so, whether it was due to one or more tempo-related problems. 623 of these reports were analysed in greater detail to identify the prevalence and characteristics of claims and related time management errors. Results The percentages of contributing factors were as follows: disease tempo, 37.9%; office tempo, 13.2%; patient tempo, 13.8%; out-of-office coordination tempo, 22.6%; and GP's access to knowledge tempo, 33.2%. Conclusion Although not conceptualised in most error taxonomies, the disease and patient tempos are cornerstones in risk management in primary care. Traditional taxonomies describe events from an analytical perspective of care at the system level and offer opportunities to improve organisation, process, and evidence-based medicine. The suggested classification describes events in terms of (unsafe) dynamic control of parallel constraints from the carer's perspective, namely the GP, and offers improvement on how to self manage and coordinate different contradictory tempos and day-to-day activities. Further work is needed to test the validity and usefulness of this approach. PMID:22927486

  18. The Microglial α7-Acetylcholine Nicotinic Receptor Is a Key Element in Promoting Neuroprotection by Inducing Heme Oxygenase-1 via Nuclear Factor Erythroid-2-Related Factor 2

    PubMed Central

    Parada, Esther; Egea, Javier; Buendia, Izaskun; Negredo, Pilar; Cunha, Ana C.; Cardoso, Silvia; Soares, Miguel P.

    2013-01-01

    Abstract Aims: We asked whether the neuroprotective effect of cholinergic microglial stimulation during an ischemic event acts via a mechanism involving the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) and/or the expression of its target cytoprotective gene, heme oxygenase-1 (HO-1). Specifically, the protective effect of the pharmacologic alpha-7 nicotinic acetylcholine receptor (α7 nAChR) agonist PNU282987 was analyzed in organotypic hippocampal cultures (OHCs) subjected to oxygen and glucose deprivation (OGD) in vitro as well as in photothrombotic stroke in vivo. Results: OHCs exposed to OGD followed by reoxygenation elicited cell death, measured by propidium iodide and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide staining. Activation of α7 nAChR by PNU282987, after OGD, reduced cell death, reactive oxygen species production, and tumor necrosis factor release. This was associated with induction of HO-1 expression, an effect reversed by α-bungarotoxin and by tin–protoporphyrin IX. The protective effect of PNU282987 was lost in microglial-depleted OHCs as well as in OHCs from Nrf2-deficient-versus-wild-type mice, an effect associated with suppression of HO-1 expression in microglia. Administration of PNU282987 1 h after induction of photothrombotic stroke in vivo reduced the infarct size and improved motor skills in Hmox1lox/lox mice that express normal levels of HO-1, but not in LysMCreHmox1Δ/Δ in which HO-1 expression is inhibited in myeloid cells, including the microglia. Innovation: This study suggests the participation of the microglial α7 nAChR in the brain cholinergic anti-inflammatory pathway. Conclusion: Activation of the α7 nAChR/Nrf2/HO-1 axis in microglia regulates neuroinflammation and oxidative stress, affording neuroprotection under brain ischemic conditions. Antioxid. Redox Signal. 19, 1135–1148. PMID:23311871