Sample records for chordata nonvertebrate

  1. Mucosal immunity in the gut: the non-vertebrate perspective. (United States)

    Garcia-Garcia, Erick; Galindo-Villegas, Jorge; Mulero, Victor


    Much is now known about the vertebrate mechanisms involved in mucosal immunity, and the requirement of commensal microbiota at mucosal surfaces for the proper functioning of the immune system. In comparison, very little is known about the mechanisms of immunity at the barrier epithelia of non-vertebrate organisms. The purpose of this review is to summarize key experimental evidence illustrating how non-vertebrate immune mechanisms at barrier epithelia compare to those of higher vertebrates, using the gut as a model organ. Not only effector mechanisms of gut immunity are similar between vertebrates and non-vertebrates, but it also seems that the proper functioning of non-vertebrate gut defense mechanisms requires the presence of a resident microbiota. As more information becomes available, it will be possible to obtain a more accurate picture of how mucosal immunity has evolved, and how it adapts to the organisms' life styles.

  2. Gout and the Risk of Non-vertebral Fracture. (United States)

    Kim, Seoyoung C; Paik, Julie M; Liu, Jun; Curhan, Gary C; Solomon, Daniel H


    Prior studies suggest an association between osteoporosis, systemic inflammation, and pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6. Conflicting findings exist on the association between hyperuricemia and osteoporosis. Furthermore, it remains unknown whether gout, a common inflammatory arthritis, affects fracture risk. Using data from a US commercial health plan (2004-2013), we evaluated the risk of non-vertebral fracture (ie, forearm, wrist, hip, and pelvis) in patients with gout versus those without. Gout patients were identified with ≥2 diagnosis codes and ≥1 dispensing for a gout-related drug. Non-gout patients, identified with ≥2 visits coded for any diagnosis and ≥1 dispensing for any prescription drugs, were free of gout diagnosis and received no gout-related drugs. Hip fracture was the secondary outcome. Fractures were identified with a combination of diagnosis and procedure codes. Cox proportional hazards models compared the risk of non-vertebral fracture in gout patients versus non-gout, adjusting for more than 40 risk factors for osteoporotic fracture. Among gout patients with baseline serum uric acid (sUA) measurements available, we assessed the risk of non-vertebral fracture associated with sUA. We identified 73,202 gout and 219,606 non-gout patients, matched on age, sex, and the date of study entry. The mean age was 60 years and 82% were men. Over the mean 2-year follow-up, the incidence rate of non-vertebral fracture per 1,000 person-years was 2.92 in gout and 2.66 in non-gout. The adjusted hazard ratio (HR) was 0.98 (95% confidence interval [CI] 0.85-1.12) for non-vertebral fracture and 0.83 (95% CI 0.65-1.07) for hip fracture in gout versus non-gout. Subgroup analysis (n = 15,079) showed no association between baseline sUA and non-vertebral fracture (HR = 1.03, 95% CI 0.93-1.15), adjusted for age, sex, comorbidity score, and number of any prescription drugs. Gout was not associated with a risk of non-vertebral

  3. FRAX and the effect of teriparatide on vertebral and non-vertebral fracture (United States)

    Harvey, Nicholas C; Kanis, John A; Odén, Anders; Burge, Russel T; Mitlak, Bruce H; Johansson, Helena; McCloskey, Eugene V


    Summary Daily teriparatide injections have been shown to reduce vertebral and non-vertebral fractures. Here we demonstrate that the magnitude of fracture risk reduction is independent of baseline fracture probability assessed by FRAX. Background Daily administration of 20μg or 40μg teriparatide has been shown to significantly decrease the risk of vertebral and non-vertebral fracture compared with placebo. The aim of the present study was to evaluate fracture risk assessed at baseline using the FRAX® tool and to determine the efficacy of teriparatide as a function of baseline fracture risk. Methods 1637 postmenopausal women in the pivotal phase 3 trial, randomly assigned to receive placebo (n=544), teriparatide 20 μg per day (n=541) or teriparatide 40 μg per day (n=552), were studied. Baseline clinical risk factors were entered into country-specific FRAX models to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. Because there was no difference in effect of 20 and 40μg teriparatide daily on fracture occurrence, the two active groups were merged. The interaction between probability of a major fracture and treatment efficacy was examined by Poisson regression. Results The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.2-67.2%. Treatment with teriparatide was associated with a 37% decrease in all non-vertebral fractures (95% CI:10-56 %) and a 56% decrease in low energy non-vertebral fractures (95% CI:24-75%) compared with placebo. The risk of morphometric vertebral fractures decreased significantly by 66% (95% CI:50-77%). Hazard ratios for the effect of teriparatide on the fracture outcome did not change significantly with increasing fracture probability (p>0.30). Similar findings were noted for the interaction when BMD was excluded from the FRAX model, or when probability of hip fracture was used as the marker of baseline risk. Conclusion We conclude that teriparatide

  4. Direct medical resource utilization associated with osteoporosis-related nonvertebral fractures in postmenopausal women. (United States)

    Jean, Sonia; Bessette, Louis; Belzile, Etienne L; Davison, K Shawn; Candas, Bernard; Morin, Suzanne; Dodin, Sylvie; Brown, Jacques P


    The purposes of this study were to assess direct medical resource utilization related to the treatment of nonvertebral osteoporotic fractures within 1 year postfracture and to evaluate whether age impacts resource utilization. A previously-validated algorithm for physician claims databases identified 15,327 women aged 50 years or older with incident fracture at nonvertebral osteoporotic sites between January 1, 2004 and December 31, 2005. Administrative databases of the health services available to all residents in Quebec served to study fracture-related health resource utilization in the year after fracture. Data were linked by a unique personal identifier, creating a longitudinal cohort of all fracture cases for health resource utilization. The proportions of fractures treated by open reduction, closed reduction, immobilization or follow-up by an orthopedic surgeon (OS) were evaluated. The mean number of claims for consultation with an OS or other clinicians in inpatient and outpatient visits, the hospitalization rate and length of stay (LOS) were assessed. Hip/femur fractures represented the highest rate of resource utilization because the majority of them required surgery (91.1%) and hospitalization (94.5%) with a mean (median) LOS of 39.2 (31) days. However, other nonvertebral fracture types needed significant clinical care related to surgery (27.9%), follow-up consultation with an OS (77.6%), and hospitalization (27.3% of total LOS). Even pelvic fractures, which often do not require surgical treatment, commanded high resource utilization due to the high hospitalization rate (67.4%) with mean (median) LOS of 34.2 (26) days. Moreover, age was an important determinant of health resource utilization, being associated with an increased number of visits to other physicians, hospitalization, and length of hospitalization (LOS), admissions to long term care (LTC), and death. Osteoporosis-related fractures accounted for substantial healthcare resource utilization

  5. Effects of long-term strontium ranelate treatment on the risk of nonvertebral and vertebral fractures in postmenopausal osteoporosis

    DEFF Research Database (Denmark)

    Reginster, Jean-Yves; Felsenberg, Dieter; Boonen, Steven;


    to receive either strontium ranelate at 2 gm/day or placebo for 5 years. The main efficacy criterion was the incidence of nonvertebral fractures. In addition, incidence of hip fractures was assessed, by post hoc analysis, in the subset of 1,128 patients who were at high risk of fractures (age 74 years...... or older with lumbar spine and femoral neck bone mineral density T scores -2.4 or less). The incidence of new vertebral fractures was assessed, using the semiquantitative method described by Genant, in the 3,646 patients in whom spinal radiography (a nonmandatory procedure) was performed during the course...... of the study. Fracture data were analyzed using the Kaplan-Meier survival method. RESULTS: Of the 5,091 patients, 2,714 (53%) completed the study up to 5 years. The risk of nonvertebral fracture was reduced by 15% in the strontium ranelate group compared with the placebo group (relative risk 0.85 [95...

  6. Effect of osteoporosis treatments on risk of non-vertebral fractures: review and meta-analysis of intention-to-treat studies.

    NARCIS (Netherlands)

    Boonen, S.; Laan, R.F.J.M.; Barton, I.P.; Watts, N.B.


    Most osteoporosis treatments have proven efficacy in reducing the risk of vertebral fractures, whereas evidence is less straightforward for prevention of non-vertebral fractures. Conclusions as to the efficacy of a treatment should be based primarily on analyses of the intention to treat (ITT) popul

  7. Decreased Serum Insulin-like Growth Factor-I is a Risk Factor for Non-vertebral Fractures in Diabetic Postmenopausal Women. (United States)

    Miyake, Hitomi; Kanazawa, Ippei; Sugimoto, Toshitsugu


    Objective Previous studies have shown that serum insulin-like growth factor-I (IGF-I) is involved in diabetes-related bone fragility. Although lower serum levels of IGF-I are reported to be associated with a higher risk of vertebral fractures in patients with type 2 diabetes, it is unknown whether or not the serum level of IGF-I is associated with the incidence of non-vertebral fractures. Methods We investigated the relationships between the serum levels of IGF-I and the incidence of non-vertebral osteoporotic fractures in 188 men and 168 postmenopausal women with type 2 diabetes. Results A multiple logistic regression analysis adjusted for age, duration of diabetes, observation period, body mass index, HbA1c, serum creatinine, and the bone mineral density at the lumbar spine showed that the serum IGF-I level was significantly and inversely associated with the incidence of non-vertebral osteoporotic fractures in postmenopausal women (odds ratio =0.48, 95% confidential interval [CI] 0.23-0.99 per SD increase; p=0.047), but not in men. Moreover, the inverse association between the serum IGF-I level and the incidence of non-vertebral fractures remained significant after additional adjustment for insulin use, and the serum calcium and phosphate levels (odds ratio =0.48, 95% CI 0.23-0.99 per SD increase; p=0.046). Conclusion This is the first study to show that decreased serum IGF-I levels are associated with a higher risk of non-vertebral osteoporotic fractures in postmenopausal women with type 2 diabetes. Serum IGF-I could be a useful marker for assessing the incidence of osteoporotic fractures.

  8. Bone strength measured by peripheral quantitative computed tomography and the risk of nonvertebral fractures: the osteoporotic fractures in men (MrOS) study. (United States)

    Sheu, Yahtyng; Zmuda, Joseph M; Boudreau, Robert M; Petit, Moira A; Ensrud, Kristine E; Bauer, Douglas C; Gordon, Christopher L; Orwoll, Eric S; Cauley, Jane A


    Many fractures occur in individuals without osteoporosis defined by areal bone mineral density (aBMD). Inclusion of other aspects of skeletal strength may be useful in identifying at-risk subjects. We used surrogate measures of bone strength at the radius and tibia measured by peripheral quantitative computed tomography (pQCT) to evaluate their relationships with nonvertebral fracture risk. Femoral neck (FN) aBMD, measured by dual-energy X-ray absorptiometry (DXA), also was included. The study population consisted of 1143 white men aged 69+ years with pQCT measures at the radius and tibia from the Minneapolis and Pittsburgh centers of the Osteoporotic Fractures in Men (MrOS) study. Principal-components analysis and Cox proportional-hazards modeling were used to identify 21 of 58 pQCT variables with a major contribution to nonvertebral incident fractures. After a mean 2.9 years of follow-up, 39 fractures occurred. Men without incident fractures had significantly greater bone mineral content, cross-sectional area, and indices of bone strength than those with fractures by pQCT. Every SD decrease in the 18 of 21 pQCT parameters was significantly associated with increased fracture risk (hazard ration ranged from 1.4 to 2.2) independent of age, study site, body mass index (BMI), and FN aBMD. Using area under the receiver operation characteristics curve (AUC), the combination of FN aBMD and three radius strength parameters individually increased fracture prediction over FN aBMD alone (AUC increased from 0.73 to 0.80). Peripheral bone strength measures are associated with fracture risk and may improve our ability to identify older men at high risk of fracture.

  9. Metal dealing at the origin of the Chordata phylum: the metallothionein system and metal overload response in amphioxus.

    Directory of Open Access Journals (Sweden)

    Maria Guirola

    Full Text Available Non-vertebrate chordates, specifically amphioxus, are considered of the utmost interest for gaining insight into the evolutionary trends, i.e. differentiation and specialization, of gene/protein systems. In this work, MTs (metallothioneins, the most important metal binding proteins, are characterized for the first time in the cephalochordate subphylum at both gene and protein level, together with the main features defining the amphioxus response to cadmium and copper overload. Two MT genes (BfMT1 and BfMT2 have been identified in a contiguous region of the genome, as well as several ARE (antioxidant response element and MRE (metal response element located upstream the transcribed region. Their corresponding cDNAs exhibit identical sequence in the two lancelet species (B. floridae and B. lanceolatum, BfMT2 cDNA resulting from an alternative splicing event. BfMT1 is a polyvalent metal binding peptide that coordinates any of the studied metal ions (Zn, Cd or Cu rendering complexes stable enough to last in physiological environments, which is fully concordant with the constitutive expression of its gene, and therefore, with a metal homeostasis housekeeping role. On the contrary, BfMT2 exhibits a clear ability to coordinate Cd(II ions, while it is absolutely unable to fold into stable Cu (I complexes, even as mixed species. This identifies it as an essential detoxification agent, which is consequently only induced in emergency situations. The cephalochordate MTs are not directly related to vertebrate MTs, neither by gene structure, protein similarity nor metal-binding behavior of the encoded peptides. The closest relative is the echinoderm MT, which confirm proposed phylogenetic relationships between these two groups. The current findings support the existence in most organisms of two types of MTs as for their metal binding preferences, devoted to different biological functions: multivalent MTs for housekeeping roles, and specialized MTs that evolve

  10. Bone turnover markers are associated with higher cortical porosity, thinner cortices, and larger size of the proximal femur and non-vertebral fractures. (United States)

    Shigdel, Rajesh; Osima, Marit; Ahmed, Luai A; Joakimsen, Ragnar M; Eriksen, Erik F; Zebaze, Roger; Bjørnerem, Åshild


    Bone turnover markers (BTM) predict bone loss and fragility fracture. Although cortical porosity and cortical thinning are important determinants of bone strength, the relationship between BTM and cortical porosity has, however, remained elusive. We therefore wanted to examine the relationship of BTM with cortical porosity and risk of non-vertebral fracture. In 211 postmenopausal women aged 54-94 years with non-vertebral fractures and 232 age-matched fracture-free controls from the Tromsø Study, Norway, we quantified femoral neck areal bone mineral density (FN aBMD), femoral subtrochanteric bone architecture, and assessed serum levels of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX). Fracture cases exhibited higher PINP and CTX levels, lower FN aBMD, larger total and medullary cross-sectional area (CSA), thinner cortices, and higher cortical porosity of the femoral subtrochanter than controls (p≤0.01). Each SD increment in PINP and CTX was associated with 0.21-0.26 SD lower total volumetric BMD, 0.10-0.14 SD larger total CSA, 0.14-0.18 SD larger medullary CSA, 0.13-0.18 SD thinner cortices, and 0.27-0.33 SD higher porosity of the total cortex, compact cortex, and transitional zone (all p≤0.01). Moreover, each SD of higher PINP and CTX was associated with increased odds for fracture after adjustment for age, height, and weight (ORs 1.49; 95% CI, 1.20-1.85 and OR 1.22; 95% CI, 1.00-1.49, both pfracture after accounting for FN aBMD, cortical porosity or cortical thickness (OR ranging from 1.31 to 1.39, p ranging from 0.005 to 0.028). In summary, increased BTM levels are associated with higher cortical porosity, thinner cortices, larger bone size and higher odds for fracture. We infer that this is produced by increased periosteal apposition, intracortical and endocortical remodeling; and that these changes in bone architecture are predisposing to fracture.

  11. The Vitamin D Assessment (ViDA) Study: design of a randomized controlled trial of vitamin D supplementation for the prevention of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures. (United States)

    Scragg, Robert; Waayer, Debbie; Stewart, Alistair W; Lawes, Carlene M M; Toop, Les; Murphy, Judy; Khaw, Kay-Tee; Camargo, Carlos A


    Observational studies have shown that low vitamin D status is associated with an increased risk of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures. We recruited 5110 Auckland adults, aged 50-84 years, into a randomized, double-blind, placebo-controlled trial to test whether vitamin D supplementation protects against these four major outcomes. The intervention is a monthly cholecalciferol dose of 100,000IU (2.5mg) for an estimated median 3.3 years (range 2.5-4.2) during 2011-2015. Participants were recruited primarily from family practices, plus community groups with a high proportion of Maori, Pacific, or South Asian individuals. The baseline evaluation included medical history, lifestyle, physical measurements (e.g. blood pressure, arterial waveform, lung function, muscle function), and a blood sample (stored at -80°C for later testing). Capsules are being mailed to home addresses with a questionnaire to collect data on non-hospitalized outcomes and to monitor adherence and potential adverse effects. Other data sources include New Zealand Ministry of Health data on mortality, hospitalization, cancer registrations and dispensed pharmaceuticals. A random sample of 438 participants returned for annual collection of blood samples to monitor adherence and safety (hypercalcemia), including repeat physical measurements at 12 months follow-up. The trial will allow testing of a priori hypotheses on several other endpoints including: weight, blood pressure, arterial waveform parameters, heart rate variability, lung function, muscle strength, gait and balance, mood, psoriasis, bone density, and chronic pain.

  12. The eukaryotic promoter database in its 30th year: focus on non-vertebrate organisms (United States)

    Dreos, René; Ambrosini, Giovanna; Groux, Romain; Cavin Périer, Rouaïda; Bucher, Philipp


    We present an update of the Eukaryotic Promoter Database EPD (, more specifically on the EPDnew division, which contains comprehensive organisms-specific transcription start site (TSS) collections automatically derived from next generation sequencing (NGS) data. Thanks to the abundant release of new high-throughput transcript mapping data (CAGE, TSS-seq, GRO-cap) the database could be extended to plant and fungal species. We further report on the expansion of the mass genome annotation (MGA) repository containing promoter-relevant chromatin profiling data and on improvements for the EPD entry viewers. Finally, we present a new data access tool, ChIP-Extract, which enables computational biologists to extract diverse types of promoter-associated data in numerical table formats that are readily imported into statistical analysis platforms such as R. PMID:27899657

  13. Molecular signatures that are distinctive characteristics of the vertebrates and chordates and supporting a grouping of vertebrates with the tunicates. (United States)

    Gupta, Radhey S


    Members of the phylum Chordata and the subphylum Vertebrata are presently distinguished solely on the basis of morphological characteristics. The relationship of the vertebrates to the two non-vertebrate chordate subphyla is also a subject of debate. Analyses of protein sequences have identified multiple conserved signature indels (CSIs) that are specific for Chordata or for Vertebrata. Five CSIs in 4 important proteins are specific for the Vertebrata, whereas two other CSIs are uniquely found in all sequenced chordate species including Ciona intestinalis and Oikapleura dioica (Tunicates) as well as Branchiostoma floridae (Cephalochordates). The shared presence of these molecular signatures by all vertebrates/chordate species, but in no other animal taxa, strongly indicates that the genetic changes represented by the identified CSIs diagnose monophyletic groups. Two other discovered CSIs are uniquely shared by different vertebrate species and by either one (Ciona intestinalis) or both tunicate (Ciona and Oikapleura) species, but they are not found in Branchiostoma or other animal species. Specific presence of these CSIs in different vertebrates and either one or both tunicate species provides strong independent evidence that the vertebrate species are more closely related to the urochordates (tunicates) than to the cephalochordates.

  14. El aparato urogenital del pecarí de collar (Pecari tajacu Chordata: Artiodactyla: un estudio anatómico

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    María Vargas García


    Full Text Available la finalidad de incrementar la información sobre la fisiología reproductiva del pecarí de collar (Pecari tajacu se realizó una descripción anatómica del aparato urogenital (au de esta especie. Se utilizaron ocho hembras y cinco machos que fueron anestesiados y perfundidos con solución de McKormik. Se realizaron disecciones para extraer el au y se describieron sus componentes. El au del pecarí de collar es característico del mamífero pero presenta similitudes con el au del cerdo. Este trabajo es el primer reporte donde se describe un seno urogenital, las glándulas vestibulares y la musculatura estriada asociada a la vulva. Es también, el primer reporte del au masculino del pecarí de collar, encontrándose algunas características exclusivas de esta especie.

  15. Mamíferos (Chordata: Mammalia florestais de médio e grande porte registrados em Barreiro Rico, Anhembi, Estado de São Paulo. Mammals (Chordata: Mammalia recorded in Barreiro Rico, state of São Paulo, Southeastern Brazil.

    Directory of Open Access Journals (Sweden)

    Alexsander Zamorano ANTUNES


    Full Text Available O presente trabalho visa ao levantamentoda riqueza e abundância relativa das espécies demamíferos de médio e grande porte encontradasem um fragmento de Floresta EstacionalSemidecidual, localizado em Barreiro Rico,município de Anhembi, Estado de São Paulo.Foram amostradas trilhas e estradas no interiore no entorno do fragmento. As espécies foramdetectadas através de visualizações, vocalizações,carcaças e rastos. Foram registradas 30 espécies,sete delas ameaçadas de extinção no estado.A riqueza encontrada foi similar à obtida emcomparação à outras cinco reservas estaduais.Entretanto, a composição de espécies diferiu entreessas áreas, devido a fatores biogeográficos e àsdiferenças na intensidade dos processos defragmentação florestal e de caça. Para conservar amastofauna de Barreiro Rico é necessária afiscalização para coibir a caça e ações de manejo,visando ao aumento da área florestal disponível eà prevenção da degradação da vegetação.This study presents the medium and largesized mammal species recorded in a semideciduousforest fragment of 1,451 ha, located in BarreiroRico (22º 45’ S and 48º 09’ W, Anhembi, in thestate of São Paulo, Southeastern Brazil. Trails androads were sampled inside the fragment and in theedges. The mammals were recorded through sight,vocalizations, carcasses and tracks. We recordedthirty species, seven threatened in São Paulo.Compared with another five forests, Barreiro Ricoshowed similar species richness. However,the species composition differs between areas, dueto biogeographic factors and differentiated impactsof forest fragmentation and hunting. To conservethe diverse Barreiro Rico mammalian fauna, it isnecessary efficient control of hunting and urgentmanagement, aiming to enlarge the fragment areaand prevent the gradual vegetation deterioration.

  16. Macrobenthic Communities of the Lower Chesapeake Bay. (United States)


    ECHINODERMATA :ECHINOIDEA Arbacij Runlctulata (Lamarck) Echinarachnius Parma (Larmack) ECHINODERMATA :HOLOTHURO-DEA Holothuroidea spp. Leptosynapta ... inhaerens (Ayres) ECHINODERMATA :OPHIUROIDEA Ophiuroidea spp. * HEMICHORDATA Saccoglossus kowalewskii (Agassiz) CHORDATA :CEPHALOCHORDATA Branchiostoma


    Institute of Scientific and Technical Information of China (English)

    黎道洪; 罗蓉; 宋锡章




    Institute of Scientific and Technical Information of China (English)

    黎道洪; 罗蓉




    Institute of Scientific and Technical Information of China (English)

    郭微; 黎道洪; 杨卫成



  20. Water Quality Criteria for Disperse Red 9 (United States)


    phylum Chordata; d) planktonic crustacean; e) benthic crustacean; f) member of class Insecta ; g) member in phylum other than ;rthropoda or Chordata; and sheep. Arch. Environ. ContaM. Toxicol. 12(4):499-507. MEDLARS II (CHEMLINE). 1986. National Library of Medicine . Chemical Dictionary Online File...STATES ARMY ATTN: CHIEF, ENVIRONMENTAL QUALITY BRANCH PREVENTIVE MEDICINE DIVISION (HSHA-IPM) FORT SAM HCUSTON, TX 78234 COMMANDER US ARMY MATERIEL

  1. [Effects of zoledronic acid on osteoporosis patients in Japan. (United States)

    Tanaka, Sakae


    Zoledronic acid is a bisphosphonate with the most potent anti-bone resorbing activity. Several previous studies demonstrated that zoledronic acid once a year significantly reduced the risk of vertebral, non-vertebral, and hip fractures in postmenopausal women. In a phase Ⅲ 2-year placebo-controlled, randomized, double-blind comparative study in Japan(ZONE study)demonstrated that once-yearly infusion of zoledronic acid 5 mg increased lumbar spine and proximal femoral BMD, and reduced the incidence of vertebral and non-vertebral fractures in Japanese patients with primary osteoporosis compared to placebo.

  2. Call it sleep-what animals without backbones can tell us about the phylogeny of intrinsically generated neuromotor rhythms during early development

    Institute of Scientific and Technical Information of China (English)

    Michael A.Corner


    A comprehensive overview is presented of the literature dealing with the development of sleep-like motility and neuronal activity patterns in non-vertebrate animals.It has been established that spontaneous,periodically modulated,neurogenic bursts of movement appear to be a universal feature of prenatal behavior.New empirical data are presented showing that such 'seismic sleep' or 'rapid-body-movement' bursts in cuttlefish persist for some time after birth.Extensive ontogenetic research in both vertebrates and non-vertebrates is thus essential before current hypotheses about the phylogeny of motorically active sleep-like states can be taken seriously.

  3. Ensembl Genomes 2013: scaling up access to genome-wide data (United States)

    Ensembl Genomes ( is an integrating resource for genome-scale data from non-vertebrate species. The project exploits and extends technologies for genome annotation, analysis and dissemination, developed in the context of the vertebrate-focused Ensembl project, and provi...

  4. Ibandronate dose response is associated with increases in bone mineral density and reductions in clinical fractures: results of a meta-analysis. (United States)

    Sebba, Anthony I; Emkey, Ronald D; Kohles, Joseph D; Sambrook, Philip N


    This meta-analysis pooled data from the four phase III clinical trials of ibandronate to assess the relationship between ibandronate dose, changes in bone mineral density, and rates of both clinical and non-vertebral fractures. Individual patient data from the intent-to-treat population of the BONE, IV fracture prevention, MOBILE, and DIVA studies were included for analysis. The relationship between ibandronate dose and bone mineral density at both the lumbar spine and at the total hip was assessed qualitatively. The relationship between lumbar spine bone mineral density and clinical fracture rate, and the relationship between total hip bone mineral density and non-vertebral fracture rate, were assessed both qualitatively and using mathematical models. A total of 8710 patients were included in this analysis. Both lumbar spine and total hip bone mineral density were observed to increase with increasing ibandronate dose. The incidence of all clinical fractures was observed to decrease as lumbar spine bone mineral density increased. A statistically significant inverse linear relationship was observed between percent change in lumbar spine bone mineral density and the rate of clinical fractures (P=0.005). A non-significant curvilinear relationship was observed between percent change in total hip bone mineral density and non-vertebral fracture rate. Increased ibandronate exposure is associated with increasing gains in the lumbar spine bone mineral density and decreasing clinical fracture rates. A non-linear relationship may exist between increases in the total hip bone mineral density and non-vertebral fracture rate.

  5. Antifracture efficacy and reduction of mortality in relation to timing of the first dose of zoledronic acid after hip fracture

    DEFF Research Database (Denmark)

    Eriksen, Erik Fink; Lyles, Kenneth W; Colón-Emeric, Cathleen S


    Annual infusions of zoledronic acid (5 mg) significantly reduced the risk of vertebral, hip, and nonvertebral fractures in a study of postmenopausal women with osteoporosis and significantly reduced clinical fractures and all-cause mortality in another study of women and men who had recently unde...

  6. Network Meta-Analysis of Pharmacological Agents for Osteoporosis Treatment and Fracture Prevention

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    Xu-cheng Yang


    Full Text Available Background and Objective: Osteoporosis afflicts a large number of populations in the world and is featured by systemic impairment of bone mass and strength which may further trigger an increase in the risk of fragile fractures. This network meta-analysis (NMA is designed to distinguish therapies more preferable than others with respect to efficacy and safety. Methods: We searched the medical literature for relevant studies systematically. Both direct and indirect evidence were synthesized to compare the efficacy, described by odds ratios (OR and 95% credible intervals (CrI. Moreover, the surface under cumulative ranking curve was calculated to rank probabilities with respect to clinical outcomes. The new non-vertebral fractures, hip and wrist fractures, and adverse events were evaluated in this NMA. Results: Patients treated by alendronate, denosumab, teriparatide were associated with a reduced risk of new non-vertebral fractures compared to those treated by placebo. Alendronate, denosumab and zoledronic acid had better efficacy in preventing hip fractures. With respect to wrist fractures prevention, no significant difference was observed. Zoledronic acid exhibited significantly increased risk of adverse events than placebo, alendronate, denosumab, and raloxifene. According to SUCRA, teriparatide ranked highest in new non-vertebral fractures prevention, etidronate and denosumab balanced safety and efficacy well. Conclusion: In summary, teriparatide appeared to be the most efficacious drug for preventing new non-vertebral fractures, while etidronate and denosumab were preferable for balancing safety and efficacy well.

  7. Preceding and subsequent high- and low-trauma fracture patterns-a 13-year epidemiological study in females and males in Austria. (United States)

    Muschitz, C; Kocijan, R; Baierl, A; Dormann, R; Feichtinger, X; Haschka, J; Szivak, M; Muschitz, G K; Schanda, J; Pietschmann, P; Resch, H; Dimai, H P


    This study investigated the implication of a preceding high-trauma fracture on subsequent high- and low-trauma fractures at different skeletal sites in postmenopausal women and similarly aged men at an age range of 54 to 70 years. A preceding high-trauma fracture increases the risk of future low-trauma non-vertebral fractures including hip.

  8. Endogenous estradiol and the risk of incident fracture in postmenopausal women: the OPUS study. (United States)

    Finigan, J; Gossiel, F; Glüer, C C; Felsenberg, D; Reid, D M; Roux, C; Eastell, R


    Some, but not all, studies have found that low endogenous estradiol levels in postmenopausal women are predictive of fractures. The aim of this study was to examine the roles of endogenous estradiol (E(2)), sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) in the prediction of incident vertebral and nonvertebral fractures. The study subjects were 797 postmenopausal women from the population-based OPUS (Osteoporosis and Ultrasound Study) study. Spine radiographs and dual-energy X-ray absorptiometry scans were obtained for all subjects at baseline and 6-year follow-up. Nonfasting blood samples were taken at baseline for E(2), SHBG, DHEAS, and bone turnover markers. Incident nonvertebral fractures were self-reported and verified; vertebral fractures were diagnosed at a single center from spinal radiographs. Medical and lifestyle data were obtained by questionnaire at each visit. Thirty-nine subjects had an incident vertebral fracture and 119 a nonvertebral fracture. Estradiol in the lowest quartile predicted vertebral fracture independent of confounders including age, body mass index, bone mineral density, bone turnover, fracture history, and use of antiresorptive therapy, with an OR of 2.97 (95 % confidence interval [CI] 1.52-5.82) by logistic regression. A calculated free estradiol index was not a stronger predictor than total E(2). Higher SHBG predicted vertebral fracture independently of age and body mass index, but not independently of E(2), bone mineral density, or prevalent fracture. Low DHEAS did not predict vertebral fracture. Nonvertebral fractures were not predicted by any of E(2), SHBG, or DHEAS, either in univariate or multivariate analyses. These findings suggest that there may be mechanistic differences in the protective effect of E(2) at vertebral compared with nonvertebral sites.

  9. No association between dietary vitamin K intake and fracture risk in chinese community-dwelling older men and women: a prospective study. (United States)

    Chan, R; Leung, J; Woo, J


    Data on the association between dietary vitamin K intake and fracture risk are limited among Chinese. This study examined such an association in community-dwelling elderly in Hong Kong. We present data from 2,944 subjects (1,605 men, 1,339 women) who participated in a prospective cohort study. Baseline dietary intakes of energy, protein, calcium, vitamin D, and vitamin K were assessed using a food-frequency questionnaire. Data on incident hip fracture and nonvertebral fracture during a median of 6.9 follow-up years were collected from a hospital database. Cox regression analyses were performed with adjustments for age, education attainment, smoking status, alcohol use, body mass index, hip bone mineral density, physical activity, use of calcium supplement, and energy-adjusted nutrient intakes. There were 29 (1.8 %) men and 19 (1.4 %) women with incident hip fractures and 97 (6.0 %) men and 88 (6.6 %) women with nonvertebral fractures. The median (interquartile range) of dietary vitamin K intake was 241.8 (157.5-360.8) and 238.9 (162.4-343.6) μg/day in men and women, respectively. Similar dietary vitamin K intakes were observed between subjects with hip or nonvertebral fractures and subjects without hip or nonvertebral fractures. In both men and women, dietary vitamin K intake was not associated with fracture risks at all measured sites in either crude or adjusted models. In Chinese community-dwelling elderly, hip or nonvertebral fracture risk was not associated with dietary vitamin K intake. The high dietary vitamin K intake of the studied group may have limited the ability to detect the association between vitamin K intake and fracture risk.

  10. Taxonomy Icon Data: raccoon dog [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available raccoon dog Nyctereutes procyonoides Chordata/Vertebrata/Mammalia/Theria/Eutheria/C...reutes_procyonoides_NS.png htt...p:// http:...// ...

  11. Taxonomy Icon Data: aye-aye [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available aye-aye Daubentonia madagascariensis Chordata/Vertebrata/Mammalia/Theria/Eutheria/P...rimate Daubentonia_madagascariensis_L.png Daubentonia_madagascariensis_NL.png Daubentonia_madagascariensis_S....png Daubentonia_madagascariensis_NS.png http://bi

  12. What's in a jellyfish? Proximate and elemental composition and biometric relationships for use in biogeochemical studies


    Lucas, C.H.; Pitt, K. A.; Purcell, J.E.; Lebrato, Mario; R. H. Condon


    Many marine organisms have gelatinous bodies, but the trait is most common in the medusae (phylum Cnidaria), ctenophores (phylum Ctenophora), and the pelagic tunicates (phylum Chordata, class Thaliacea). Although there are taxonomic and trophic differences between the thaliaceans and the other two closely related phyla, the collective term "jellyfish" has been used within the framework of this article. Because of the apparent increase in bloom events, jellyfish are receiving greater attention...

  13. Water Quality Criteria for Colored Smokes: 1,4-Diamino-2,3- Dihydroanthraquinone (United States)


    crustacean; (f) member of class Insecta ; (g) member in phylum other than Arthropoda or Chordata; and, (h) member of family in any order of class Insecta or...riAl _WAste, & Lafayette, IN, May 7-9, 1974. Eng. Ext. Series No. 145. pp. 524-534. MEDIARS 11 (CHEMLINE). 1987. National Library of Medicine ...ACADEMY OF HEALTH SCIENCES UNITED STATES ARMY ATTN: CHIEF, ENVIRONMENTAL QUALITY BRANCH PREVENTIVE MEDICINE DIVISION (HSHA-TPM) FORT SAM HOUSTON, TX

  14. An update on vitamin D deficiency and at risk groups. (United States)

    Blann, Andrew


    Vitamin D is required for healthy bones. We need sunlight and good renal and liver function for the synthesis of vitamin D, although it can also be taken in diet. Severe deficiency causes the bone diseases rickets and osteomalacia. Supplementation with vitamin D can help prevent low birth weight and non-vertebral fractures. Roles for vitamin D in other aspects of health are controversial.

  15. Hormone replacement therapy and the prevention of postmenopausal osteoporosis


    Marco Gambacciani; Marco Levancini


    Fracture prevention is one of the public health priorities worldwide. Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis, the most common metabolic bone disease. Different effective treatments for osteoporosis are available. Hormone replacement therapy (HRT) at different doses rapidly normalizes turnover, preserves bone mineral density (BMD) at all skeletal sites, leading to a significant, reduction in vertebral and non-vertebral fractures. Tibolone, a ...

  16. Daphnia magna bioassays to detect novel eco-toxicological effects of prioritary and emergent contaminants


    Campos, Bruno


    There is increasing evidence that the presence of many emerging pollutants in aquatic ecosystems may have detrimental effects on aquatic biota. Of special concern are those emerging pollutants that may act as putative endocrine disrupters in non-vertebrate species, causing unexpected effects. In chapters 2, 3 and 4, I assessed the effects of two pharmaceuticals belonging to the group of "SSRIs": fluoxetine and fluvoxamine, used to treat depression; and the detergent 4-nonylphenol. SSRIs an...

  17. Taxonomy Icon Data: Magellanic penguin [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Magellanic penguin Spheniscus magellanicus Chordata/Vertebrata/Aves Spheniscus_magel...lanicus_L.png Spheniscus_magellanicus_NL.png Spheniscus_magellanicus_S.png Spheniscus_magellanicus_NS.png h...ttp://

  18. Taxonomy Icon Data: Western clawed frog [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Western clawed frog Xenopus tropicalis Chordata/Vertebrata/Amphibia Xenopus_tropicalis_L.png Xenopus..._tropicalis_NL.png Xenopus_tropicalis_S.png Xenopus_tropicalis_NS.png ...

  19. Taxonomy Icon Data: platypus [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available platypus Ornithorhynchus anatinus Chordata/Vertebrata/Mammalia/Prototheria Ornithorhynchu...s_anatinus_L.png Ornithorhynchus_anatinus_NL.png Ornithorhynchus_anatinus_S.png Ornithorhynchus_anatin...us_NS.png http://biosciencedbc.j...p/taxonomy_icon/icon.cgi?i=Ornithorhynchus+anatinus&t=S ...

  20. Taxonomy Icon Data: coelacanth [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available coelacanth Latimeria chalumnae Chordata/Vertebrata/Pisciformes Latimeria_chalumnae_L.png Latime...ria_chalumnae_NL.png Latimeria_chalumnae_S.png Latimeria_chalumnae_NS.png http://biosciencedbc.j...p/taxonomy_icon/icon.cgi?i=Latimeria+chalumnae&t=L ...

  1. Taxonomy Icon Data: lion [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available lion Panthera leo Chordata/Vertebrata/Mammalia/Theria/Eutheria/Carnivora Panthera_leo_L.png Panthera..._leo_NL.png Panthera_leo_S.png Panthera_leo_NS.png ...

  2. Taxonomy Icon Data: horse [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available horse Equus caballus Chordata/Vertebrata/Mammalia/Theria/Eutheria/etc. Equus_caballus_L.png Equus_caba...llus_NL.png Equus_caballus_S.png Equus_caballus_NS.png http:...// ...

  3. Taxonomy Icon Data: Oryzias javanicus [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Oryzias javanicus Oryzias javanicus Chordata/Vertebrata/Pisciformes Oryzias_javanicus_L.png Oryzias_java...nicus_NL.png Oryzias_javanicus_S.png Oryzias_javanicus_NS.png ... ...

  4. Taxonomy Icon Data: Javan tree shrew [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Javan tree shrew Tupaia javanica Chordata/Vertebrata/Mammalia/Theria/Eutheria/etc. Tupaia_java...nica_L.png Tupaia_javanica_NL.png Tupaia_javanica_S.png Tupaia_javanica_NS.png ...

  5. Taxonomy Icon Data: domestic pigeon [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available domestic pigeon Columba livia Chordata/Vertebrata/Aves Columba_livia_L.png Columba_livia_NL.png Columba..._livia_S.png Columba_livia_NS.png ...

  6. Taxonomy Icon Data: crested porcupine [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available crested porcupine Hystrix cristata Chordata/Vertebrata/Mammalia/Theria/Eutheria/etc. Hystrix_cristata..._L.png Hystrix_cristata_NL.png Hystrix_cristata_S.png Hystrix_cristata_NS.png ...

  7. Taxonomy Icon Data: Asiatic tapir [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Asiatic tapir Tapirus indicus Chordata/Vertebrata/Mammalia/Theria/Eutheria/etc. Tapirus_indicus_L.png Tapi...rus_indicus_NL.png Tapirus_indicus_S.png Tapirus_indicus_NS.png ...

  8. Taxonomy Icon Data: Nile crocodile [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Nile crocodile Crocodylus niloticus Chordata/Vertebrata/Reptilia/etc Crocodylus_niloticus_L.png Croco...dylus_niloticus_NL.png Crocodylus_niloticus_S.png Crocodylus_niloticus_NS.png ...

  9. Taxonomy Icon Data: Japanese Ratsnake [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Japanese Ratsnake Elaphe climacophora Chordata/Vertebrata/Reptilia/etc Elaphe_climacophora_L.png Elaphe_clim...acophora_NL.png Elaphe_climacophora_S.png Elaphe_climacophora_NS.png ...

  10. Taxonomy Icon Data: Philippine flying lemur [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Philippine flying lemur Cynocephalus volans Chordata/Vertebrata/Mammalia/Theria/Eutheria/etc. Cynocephalu...s_volans_L.png Cynocephalus_volans_NL.png Cynocephalus_volans_S.png Cynocephalus_volan...s_NS.png ...

  11. Taxonomy Icon Data: sperm whale [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available sperm whale Physeter macrocephalus Chordata/Vertebrata/Mammalia/Theria/Eutheria/Cet...acea Physeter_macrocephalus_L.png Physeter_macrocephalus_NL.png Physeter_macrocephalus_S.png Physeter_macrocephalu...s_NS.png ...

  12. Taxonomy Icon Data: southern two-toed sloth [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available southern two-toed sloth Choloepus didactylus Chordata/Vertebrata/Mammalia/Theria/Eutheria/etc. Choloe...pus_didactylus_L.png Choloepus_didactylus_NL.png Choloepus_didactylus_S.png Choloepus_dida...ctylus_NS.png ...

  13. Taxonomy Icon Data: dugong [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available dugong Dugong dugon Chordata/Vertebrata/Mammalia/Theria/Eutheria/etc. Dugong_dugon_L.png Dugong..._dugon_NL.png Dugong_dugon_S.png Dugong_dugon_NS.png ...

  14. Taxonomy Icon Data: okapi [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available okapi Okapia johnstoni Chordata/Vertebrata/Mammalia/Theria/Eutheria/Artiodactyla Okapia_john...stoni_L.png Okapia_johnstoni_NL.png Okapia_johnstoni_S.png Okapia_johnstoni_NS.png ...

  15. Is the Presence of Jellyfish Problematic or Beneficial?

    Directory of Open Access Journals (Sweden)

    Udomsak DARUMAS


    Full Text Available Jellyfish are a diverse group of animals. The group consists of Chordata, Ctenophora and, mainly, Cnidaria. Jellyfish are often thought to be harmful, but few can cause fatality in humans. They are important throughout the trophic levels and consume a variety of prey. Jellyfish are used for food and have a high potential for pharmaceutical use. During a jellyfish bloom, energy flows are shunted through the trophic levels. Additionally, unusual increases in populations of jellyfish can cause problems for fisheries, aquaculture, power plants and the tourist industries.

  16. Taxonomy Icon Data: Pacific electric ray [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Pacific electric ray Torpedo californica Chordata/Vertebrata/Pisciformes Torpedo_californica_L.png Torpedo..._californica_NL.png Torpedo_californica_S.png Torpedo_californica_NS.png ...

  17. Taxonomy Icon Data: gold crucian carp [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available gold crucian carp Carassius auratus auratus Chordata/Vertebrata/Pisciformes Carassius_auratus_aura...tus_L.png Carassius_auratus_auratus_NL.png Carassius_auratus_auratus_S.png Carassius_auratus_aura...tus_NS.png ...

  18. Taxonomy Icon Data: white-tufted-ear marmoset [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available white-tufted-ear marmoset Callithrix jacchus Chordata/Vertebrata/Mammalia/Theria/Eutheria/Primate Call...ithrix_jacchus_L.png Callithrix_jacchus_NL.png Callithrix_jacchus_S.png Callithrix_jacchu...s_NS.png ...

  19. Taxonomy Icon Data: Reeve's pond turtle [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Reeve's pond turtle Chinemys reevesii Chordata/Vertebrata/Reptilia/etc Chinemys_reevesii_L.png Chinemys_reev...esii_NL.png Chinemys_reevesii_S.png Chinemys_reevesii_NS.png http://biosciencedbc.j...p/taxonomy_icon/icon.cgi?i=Chinemys+reevesii&t=L ...

  20. Taxonomy Icon Data: southern cassowary [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available southern cassowary Casuarius casuarius Chordata/Vertebrata/Aves Casuarius_casuarius_L.png Casuarius_cas...uarius_NL.png Casuarius_casuarius_S.png Casuarius_casuarius_NS.png ...

  1. Taxonomy Icon Data: Florida lancelet (amphioxus) [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Florida lancelet (amphioxus) Branchiostoma floridae Chordata/Urochordata,Cephalochorda...ta Branchiostoma_floridae_L.png Branchiostoma_floridae_NL.png Branchiostoma_floridae_S.png Branchiostoma_florida...e_NS.png

  2. Taxonomy Icon Data: giant panda [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available giant panda Ailuropoda melanoleuca Chordata/Vertebrata/Mammalia/Theria/Eutheria/Carnivora Ailuropoda..._melanoleuca_L.png Ailuropoda_melanoleuca_NL.png Ailuropoda_melanoleuca_S.png Ailuropoda_me...lanoleuca_NS.png ...

  3. Taxonomy Icon Data: pronghorn [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available pronghorn Antilocapra americana Chordata/Vertebrata/Mammalia/Theria/Eutheria/Artiodactyla Antilocapra..._americana_L.png Antilocapra_americana_NL.png Antilocapra_americana_S.png Antilocapra_amer...icana_NS.png ...

  4. Taxonomy Icon Data: saddled bichir [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available saddled bichir Polypterus endlicheri Chordata/Vertebrata/Pisciformes Polypterus_endlicheri_L.png Polypteru...s_endlicheri_NL.png Polypterus_endlicheri_S.png Polypterus_endlicheri_NS.png ...

  5. The phylogeny of invertebrates and the evolution of myelin. (United States)

    Roots, Betty I


    Current concepts of invertebrate phylogeny are reviewed. Annelida and Arthropoda, previously regarded as closely related, are now placed in separate clades. Myelin, a sheath of multiple layers of membranes around nerve axons, is found in members of the Annelida, Arthropoda and Chordata. The structure, composition and function of the sheaths in Annelida and Arthropoda are examined and evidence for the separate evolutionary origins of myelin in the three clades is presented. That myelin has arisen independently at least three times, namely in Annelids, Arthropodas and Chordates, provides a remarkable example of convergent evolution.

  6. Taxonomy Icon Data: Southern elephant seal [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Southern elephant seal Mirounga leonina Chordata/Vertebrata/Mammalia/Theria/Eutheria/Carnivora Mirounga_leon...ina_L.png Mirounga_leonina_NL.png Mirounga_leonina_S.png Mirounga_leonina_NS.png ...

  7. Taxonomy Icon Data: gray short-tailed opossum [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available gray short-tailed opossum Monodelphis domestica Chordata/Vertebrata/Mammalia/Theria.../Metatheria Monodelphis_domestica_L.png Monodelphis_domestica_NL.png Monodelphis_domestica_S.png Monodelphis_domestic...a_NS.png ...

  8. Taxonomy Icon Data: pig [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available pig Sus scrofa domestica Chordata/Vertebrata/Mammalia/Theria/Eutheria/Artiodactyla Sus_scrofa_domestic...a_L.png Sus_scrofa_domestica_NL.png Sus_scrofa_domestica_S.png

  9. Taxonomy Icon Data: Chinchilla [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Chinchilla Chinchilla lanigera Chordata/Vertebrata/Mammalia/Theria/Eutheria/etc. Chinchill...a_lanigera_L.png Chinchilla_lanigera_NL.png Chinchilla_lanigera_S.png Chinchilla_lanigera_NS.png http...:// ...

  10. Taxonomy Icon Data: Eastern Gorilla [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Eastern Gorilla Gorilla beringei Chordata/Vertebrata/Mammalia/Theria/Eutheria/Primate Gorill...a_beringei_L.png Gorilla_beringei_NL.png Gorilla_beringei_S.png Gorilla_beringei_NS.png ...

  11. Taxonomy Icon Data: California sea lion [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available California sea lion Zalophus californianus Chordata/Vertebrata/Mammalia/Theria/Euth...eria/Carnivora Zalophus_californianus_L.png Zalophus_californianus_NL.png Zalophus_californianus_S.png Zalophus_california...nus_NS.png ...

  12. Taxonomy Icon Data: Asiatic elephant [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Asiatic elephant Elephas maximus Chordata/Vertebrata/Mammalia/Theria/Eutheria/etc. Elephas_maximus..._L.png Elephas_maximus_NL.png Elephas_maximus_S.png Elephas_maximus_NS.png ...

  13. Lysozymes in the animal kingdom

    Indian Academy of Sciences (India)

    Lien Callewaert; Chris W Michiels


    Lysozymes (EC are hydrolytic enzymes, characterized by their ability to cleave the -(1,4)-glycosidic bond between -acetylmuramic acid and -acetylglucosamine in peptidoglycan, the major bacterial cell wall polymer. In the animal kingdom, three major distinct lysozyme types have been identified – the c-type (chicken or conventional type), the g-type (goose-type) and the i-type (invertebrate type) lysozyme. Examination of the phylogenetic distribution of these lysozymes reveals that c-type lysozymes are predominantly present in the phylum of the Chordata and in different classes of the Arthropoda. Moreover, g-type lysozymes (or at least their corresponding genes) are found in members of the Chordata, as well as in some bivalve mollusks belonging to the invertebrates. In general, the latter animals are known to produce i-type lysozymes. Although the homology in primary structure for representatives of these three lysozyme types is limited, their three-dimensional structures show striking similarities. Nevertheless, some variation exists in their catalytic mechanisms and the genomic organization of their genes. Regarding their biological role, the widely recognized function of lysozymes is their contribution to antibacterial defence but, additionally, some lysozymes (belonging to different types) are known to function as digestive enzymes.

  14. Lasofoxifene: Evidence of its therapeutic value in osteoporosis

    Directory of Open Access Journals (Sweden)

    Luigi Gennari


    Full Text Available Luigi Gennari, Daniela Merlotti, Vincenzo De Paola, Ranuccio NutiDepartment of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Policlinico Le Scotte 53100-Siena, ItalyIntroduction: Osteoporosis is a skeletal disorder characterized by compromised bone strength and increased risk of fracture. It is a common disorder in elderly subjects and represents a major public health problem, affecting up to 40% postmenopausal women and 15% of men. Among the several therapeutical interventions, hormone replacement therapy (HRT was traditionally seen as the gold standard for preventing osteoporotic fractures in postmenopausal women, as well as for the management of menopausal symptoms. However HRT, especially if administered long-term, may lead to an increased risk of breast and, when unopposed by progestins, endometrial cancers. Alternative therapies include bisphosphonates and raloxifene, a selective estrogen receptor modulator (SERM. While the former have been associated with suboptimal adherence, the latter was considerably less potent than estrogen and its effect in the prevention of nonvertebral fractures remain uncertain. Aims: The purpose of this article is to review the clinical trials of lasofoxifene, a new SERM for the treatment of postmenopausal osteoporosis. The medical literature was reviewed for appropriate articles containing the terms “lasofoxifene” and SERMs”. Evidence review: There are three (phase II or phase III clinical trials that clearly demonstrate efficacy and safety of this new SERM in the suppression of bone loss and the prevention of vertebral and nonvertebral fractures. Moreover, lasofoxifene treatment also reduced breast cancer risk and the occurrence of vaginal atrophy.Place in therapy: With its increased potency and efficacy on the prevention of nonvertebral fractures lasofoxifene may be an alternative and cost-effective therapy for osteoporosis in postmenopausal women

  15. A new hypothesis for the importance of seed dispersal in time. (United States)

    Guzmán, Adriana; Stevenson, Pablo R


    Most studies on seed dispersal in time have focused on seed dormancy and the physiological triggers for germination. However, seed dispersed by animals with low metabolic and moving rates, and long gut-passage times such as terrestrial turtles, could be considered another type of dispersal in time. This study tests the hypothesis that seeds dispersed in time may lower predation rates. We predicted that seeds deposited below parent trees after fruiting fall has finished is advantageous to minimize seed predators and should show higher survival rates. Four Amazonian plant species, Dicranostyles ampla, Oenocarpus bataua, Guatteria atabapensis and Ocotea floribunda, were tested for seed survival probabilities in two periods: during fruiting and 10-21 days after fruiting. Experiments were carried out in two biological stations located in the Colombian Amazon (Caparú and Zafire Biological Stations). Seed predation was high and mainly caused by non-vertebrates. Out of the four plant species tested, only Guatteria atabapensis supported the time escape hypothesis. For this species, seed predation by vertebrates after the fruiting period increased (from 4.1% to 9.2%) while seed predation by non-vertebrates decreased (from 54.0% to 40.2%). In contrast, seed predation by vertebrates and by non-vertebrates after the fruiting period in D. ampla increased (from 7.9% to 22.8% and from 40.4% to 50.6%, respectively), suggesting predator satiation. Results suggest that for some species dispersal in time could be advantageous to avoid some type of seed predators. Escape in time could be an additional dimension in which seeds may reach adequate sites for recruitment. Thus, future studies should be address to better understand the survival advantages given by an endozoochory time-dispersal process.

  16. Teriparatide (recombinant human parathyroid hormone 1-34 in postmenopausal women with osteoporosis: systematic review

    Directory of Open Access Journals (Sweden)

    Virgínia Fernandes Moça Trevisani

    Full Text Available CONTEXT AND OBJECTIVE: Osteoporosis is defined as a disease characterized by low bone mass and deterioration of the bone tissue microarchitecture. Teriparatide stimulates the formation and action of osteoblasts, which are responsible for bone formation, thus promoting bone tissue increase. The aim was to assess the effectiveness and safety of teriparatide for treating postmenopausal osteoporosis. METHODS: A systematic review was conducted using the Cochrane Collaboration methodology. RESULTS: 1 Teriparatide 20 µg or 40 µg versus placebo: there was a benefit from teriparatide, considering the following outcomes: reduction in the number of new vertebral and non-vertebral fractures, and increased whole-body, lumbar and femoral bone mineral density. 2 Teriparatide 40 µg versus alendronate 10 mg/day for 14 months: there was no statistical difference regarding the incidence of new vertebral or non-vertebral fractures, although in the group that received teriparatide there was greater bone mineral density increase in the whole body, lumbar column and femur. 3 Estrogen plus teriparatide 25 µg versus estrogen: there was a benefit, considering the following outcomes: reduction in the number of new vertebral fractures, and increased whole-body, lumbar and femoral bone mineral density after three years. CONCLUSIONS: When teriparatide is intermittently administered in low doses, it reduces the incidence of vertebral fractures (67% and non-vertebral fractures (38% and increases bone mineral density in the lumbar column and femur. There is a need for studies with longer observation in order to allow conclusions regarding the safety and duration of the therapeutic effects.

  17. Drug-Related Adverse Events of Osteoporosis Therapy. (United States)

    Khan, Moin; Cheung, Angela M; Khan, Aliya A


    Postmenopausal osteoporosis is associated with microarchitectural deterioration and increased risk of fracture. Osteoporosis therapy effectively reduces the risk of vertebral, nonvertebral, and hip fracture and has been associated with increased survival. Currently approved treatments for osteoporosis include bisphosphonates, denosumab, selective estrogen receptor modulators, and teriparatide. This article reviews the adverse events of therapy associated with these medical interventions. Hormone replacement therapy is not included, because it is no longer indicated for the treatment of osteoporosis in all countries. Calcitonin and strontium ranelate are also not included, because their indication for osteoporosis has recently been limited or withdrawn.

  18. Protozoan Acanthamoeba polyphaga as a potential reservoir for Campylobacter jejuni. (United States)

    Axelsson-Olsson, Diana; Waldenström, Jonas; Broman, Tina; Olsen, Björn; Holmberg, Martin


    We showed by a laboratory experiment that four different Campylobacter jejuni strains are able to infect the protozoan Acanthamoeba polyphaga. C. jejuni cells survived for longer periods when cocultured with amoebae than when grown in culture alone. The infecting C. jejuni cells aggregated in amoebic vacuoles, in which they were seen to be actively moving. Furthermore, a resuscitation of bacterial cultures that were previously negative in culturability tests was observed after reinoculation into fresh amoeba cultures. After spontaneous rupture of the amoebae, C. jejuni could be detected by microscopy and culturability tests. Our results indicate that amoebae may serve as a nonvertebrate reservoir for C. jejuni in the environment.

  19. Generalized osteoporosis of mixed origin with severe compression fractures and pain syndrome

    Directory of Open Access Journals (Sweden)

    A K Lipatenkova


    Full Text Available He main issue in osteoporosis management is the duration of treatment with different drugs particularly in cases of severe osteoporosis with high fracture risks and indications of switching from one to other agents. Denosumab is a new class of osteoporosis treatment called a human monoclonal antibody that prevents RANKL-RANK interaction and thereby inhibits osteoclast formation, demonstrates significant efficacy for vertebral, nonvertebral and hip fracture risk reduction. This case demonstrates multifactorial reasons for osteoporosis development (postmenopausal osteoporosis, primary hyperparathyroidism, as well as the long-term applying of different osteoporosis drugs with various actions mechanisms and different effectiveness.

  20. Relationship between bone mineral density changes and fracture risk reduction in patients treated with strontium ranelate

    DEFF Research Database (Denmark)

    Bruyere, Olivier; Roux, Christian; Detilleux, Johann;


    Of Peripheral OSteoporosis study were evaluated. OUTCOME MEASURES: The outcome measures included BMD at the lumbar spine, femoral neck, and total proximal femur assessed at baseline and after a follow-up of 1 and 3 yr; semiquantitative visual assessment of vertebral fractures; and nonvertebral fractures based...... on written documentation. RESULTS: After 3 yr of strontium ranelate treatment, each percentage point increase in femoral neck and total proximal femur BMD was associated with a 3% (95% adjusted confidence interval, 1-5%) and 2% (1-4%) reduction in risk of a new vertebral fracture, respectively. The 3-yr...

  1. What is microglia neurotoxicity (Not)?

    DEFF Research Database (Denmark)

    Biber, Knut; Owens, Trevor; Boddeke, Erik


    Microglia most likely appeared early in evolution as they are not only present in vertebrates, but are also found in nervous systems of various nonvertebrate organisms. Mammalian microglia are derived from a specific embryonic, self-renewable myeloid cell population that is throughout lifetime...... the difficulty to discriminate microglia and peripheral myeloid cells in the diseased brain. On the other hand it is described that a more functional approach by mutating, inactivating or deleting microglia is seldom associated with a beneficial outcome in an acute injury situation, suggesting that microglia...

  2. Efficacy and safety of risedronate 150 mg once a month in the treatment of postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    Paula Rackoff


    Full Text Available Paula RackoffDivision of Rheumatology, Beth Israel Medical Center, New York, NY, USAAbstract: Fragility fractures that occur as a result of osteoporosis are frequently associated with chronic pain and decreased quality of life as well as significant morbidity and mortality. Fracture reduction, however, is often less than optimal due to poor compliance with medications. Studies have demonstrated that risedronate, a heterocyclic nitrogen containing bisphosphonate can reduce vertebral, nonvertebral, and hip fracture incidence in postmenopausal women, in men, and in subsets of older patients at great risk of falls and fragility. The mechanism, efficacy, dosing options, and tolerability of risedronate are reviewed.Keywords: osteoporosis, fracture

  3. The bisphosphonates: risks and benefits of long term use

    DEFF Research Database (Denmark)

    Hermann, Anne Pernille; Abrahamsen, Bo


    Bisphosphonates are widely used globally as the main treatment for osteoporosis. Both safety and efficacy have only been rigorously evaluated in studies of relatively short duration (3-5 years), with smaller extension studies. The evidence for benefit beyond five years in intervention studies...... is limited and does not include proven efficacy against nonvertebral fractures. Observational studies suggest a sustained benefit against hip fractures. Bisphosphonates are stored in the skeleton for months to years, depending on the degree of bone turnover and the binding properties of the bisphosphonate...

  4. Selective estrogen receptor modulator (SERM for the treatment of osteoporosis in postmenopausal women: focus on lasofoxifene

    Directory of Open Access Journals (Sweden)

    Luigi Gennari


    Full Text Available Luigi Gennari, Daniela Merlotti, Ranuccio NutiDepartment of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Siena, ItalyAbstract: Selective estrogen receptor modulators (SERMs represent a class with a growing number of compounds that act as either estrogen receptor agonists or antagonists in a tissuespecific manner. This article reviews lasofoxifene, a new-generation SERM that has completed phase III development for the prevention and treatment of osteoporosis in postmenopausal women. Consistent with preclinical observations, this new SERM demonstrated improved skeletal efficacy over raloxifene and at an oral dose of 0.5 mg/day was effective in the prevention of both vertebral and nonvertebral fractures in postmenopausal women with osteoporosis. At the same dosage, lasofoxifene treatment also reduced estrogen receptor-positive breast cancer risk and the occurrence of vaginal atrophy, but, like the other SERMs, was associated with hot flushes and an increased risk of venous thromboembolic events. With its increased efficacy on the prevention of nonvertebral fractures than current available SERMs and its positive effects on the vagina, this new compound may represent an alternative and cost-effective therapy for osteoporosis in postmenopausal women.Keywords: SERM, lasofoxifene, postmenopausal osteoporosis, fractures, bone density, menopause

  5. Bazedoxifene: a review of its use in the treatment of postmenopausal osteoporosis. (United States)

    Duggan, Sean T; McKeage, Kate


    Bazedoxifene (Conbriza®, Viviant®) is the first third-generation selective estrogen receptor modulator (SERM) and it is approved for the treatment of postmenopausal osteoporosis in the EU and Japan. Bazedoxifene contains an indole-based core binding domain that binds with high affinity to estrogen receptors and exhibits favourable effects on bone and lipid profiles, with no clinically relevant endometrial or breast stimulation. Oral bazedoxifene once daily reduced the incidence of new vertebral fractures in patients with postmenopausal osteoporosis in a large, well designed trial of 3 years' duration; both bazedoxifene and raloxifene were significantly more effective than placebo. Neither bazedoxifene nor raloxifene reduced the incidence of nonvertebral fractures in the overall study population; however, bazedoxifene, but not raloxifene, reduced the rate of nonvertebral fractures in high-risk patients. Moreover, data from patients who continued to receive the drug during a 2-year extension phase of this trial indicate that bazedoxifene continues to provide protection against new vertebral fractures for up to 5 years. Bazedoxifene also increases bone mineral density and reduces the levels of bone turnover markers. Bazedoxifene was generally well tolerated and did not detrimentally affect the reproductive tract or breast tissue in clinical trials, thereby demonstrating a favourable risk-benefit profile. A pharmacoeconomic analysis conducted from an EU perspective predicted bazedoxifene to be cost effective in some EU countries. Therefore, bazedoxifene presents another useful option for the treatment of postmenopausal osteoporosis, especially in those at high risk for osteoporotic fracture.

  6. Vitamin D and bone health in postmenopausal women. (United States)

    Malabanan, Alan O; Holick, Michael F


    Osteoporosis, a disease of increased skeletal fragility, is becoming increasingly common as the U.S. population ages. Adequate vitamin D and calcium intake is the cornerstone of osteoporosis prevention and treatment. Age-related changes in vitamin D and calcium metabolism increase the risk of vitamin D insufficiency and secondary hyperparathyroidism. Although longitudinal data have suggested a role of vitamin D intake in modulating bone loss in perimenopausal women, studies of vitamin D and calcium supplementation have failed to support a significant effect of vitamin D and calcium during early menopause. There is a clearer benefit in vitamin D and calcium supplementation in older postmenopausal women. Vitamin D intake between 500 and 800 IU daily, with or without calcium supplementation, has been shown to increase bone mineral density (BMD) in women with a mean age of approximately 63 years. In women older than 65, there is even more benefit with vitamin D intakes of between 800 and 900 IU daily and 1200-1300 mg of calcium daily, with increased bone density, decreased bone turnover, and decreased nonvertebral fractures. The decreases in nonvertebral fractures may also be influenced by vitamin D-mediated decreases in body sway and fall risk. There are insufficient available data supporting a benefit from vitamin D supplementation alone, without calcium, to prevent osteoporotic fracture in postmenopausal women.

  7. Evidence for the Treatment of Osteoporosis with Vitamin D in Residential Care and in the Community Dwelling Elderly

    Directory of Open Access Journals (Sweden)

    John A. A. Geddes


    Full Text Available Introduction. Vitamin D is common treatment for osteoporosis. Both age >70 years and living in residential care are associated with increased fracture risk. Community dwelling elderly are a heterogeneous group who may have more similatiry with residential care groups than younger community dwelling counterparts. Aims. To review the evidence for cholecalciferol or ergocalciferol tretment of osteoporosis in either community dwelling patients aged ≥70 years of age, or redidential care patients. Secondly endpoints were changes in bone mineral denisty, and in bone turnover markers. Methods. We performed a literature search using search terms for osteoporosis and vitamin D. Treatment for at least one year was required. Results. Only one residential care study using cholecalciferol, showed non-vertebral and hip fracture reduction in vitamin D deficient subjects. In the community setting one quasi randomised study using ergocalciferol showed reduction in total but not hip or non-vertebral fracture, and a second randomised study showed increased hip fracture risk. Three studies reported increases in hip bone mineral denisty. Discussion. A minority of studies demonstrated a fracture benefit form vitamin D and one suggested possible harm in a community setting. Current practice should be to only offer this treatment to subjects identified as deficient.

  8. Fragility Fractures in Patients with Psoriatic Arthritis. (United States)

    Del Puente, Antonio; Esposito, Antonella; Costa, Luisa; Benigno, Carla; Del Puente, Aurora; Foglia, Francesca; Oriente, Alfonso; Bottiglieri, Paolo; Caso, Francesco; Scarpa, Raffaele


    Psoriatic arthritis (PsA) can have peculiar effects on bone, including mechanisms of bone loss such as erosions, but also of bone formation, such as ankylosis or periostitis. The aim of the present study was to describe the prevalence of fractures in patients with PsA as compared to healthy controls and to investigate determinants of fractures among cases. For both cases and controls, radiographs were read to identify vertebral fractures (VF), and the presence of femoral neck or other nonvertebral fractures was obtained from patients' medical history. The prevalence of fragility fractures on radiographic readings did not differ between cases and controls. The number of subjects showing a VF was 33 (36%) among PsA patients and 36 (36%) among controls, with a prevalence of severe VF of 8% among cases and 4% among controls. Controlling for covariates in a logistic model, the only variables showing a significant correlation with the presence of nonvertebral fractures (NVF) were disease duration (p=0.02), age (p=0.03), and bone mineral density at femoral neck (inverse correlation, p=0.04). Fractures should be carefully considered when evaluating the global picture of the patient with PsA for their contribution to the "fragility" profile.

  9. The Tromsø Study: body height, body mass index and fractures. (United States)

    Joakimsen, R M; Fønnebø, V; Magnus, J H; Tollan, A; Søgaard, A J


    Tall persons suffer more hip fractures than shorter persons, and high body mass index is associated with fewer hip and forearm fractures. We have studied the association between body height, body mass index and all non-vertebral fractures in a large, prospective, population-based study. The middle-aged population of Tromsø, Norway, was invited to surveys in 1979/80, 1986/87 and 1994/95 (The Tromsø Study). Of 16,676 invited to the first two surveys, 12,270 attended both times (74%). Height and weight were measured without shoes at the surveys, and all non-vertebral fractures in the period 1988-1995 were registered (922 persons with fractures) and verified by radiography. The risk of a low-energy fracture was found to be positively associated with increasing body height and with decreasing body mass index. Furthermore, men who had gained weight had a lower risk of hip fractures, and women who had gained weight had a lower risk of fractures in the lower extremities. High body height is thus a risk factor for fractures, and 1 in 4 low-energy fractures among women today might be ascribed to the increase in average stature since the turn of the century. Low body mass index is associated with a higher risk of fractures, but the association is probably too weak to have any clinical relevance in this age category.

  10. Novel therapies for osteoporosis. (United States)

    Makras, Polyzois; Delaroudis, Sideris; Anastasilakis, Athanasios D


    Since the identification of osteoporosis as a major health issue in aging populations and the subsequent development of the first treatment modalities for its management, considerable progress has been made in our understanding of the mechanisms controlling bone turnover and disease pathophysiology, thus enabling the pinpointing of new targets for intervention. This progress, along with advances in biotechnology, has rendered possible the development of ever more sophisticated treatments employing novel mechanisms of action. Denosumab, a monoclonal antibody against RANKL, approved for the treatment of postmenopausal and male osteoporosis, significantly and continuously increases bone mineral density (BMD) and maintains a low risk of vertebral, non-vertebral, and hip fractures for up to 8 years. Currently available combinations of estrogens with selective estrogen receptor modulators moderately increase BMD without causing the extra-skeletal adverse effects of each compound alone. The cathepsin K inhibitor odanacatib has recently been shown to decrease vertebral, non-vertebral, and hip fracture rates and is nearing approval. Romosozumab, an anti-sclerosin antibody, and abaloparatide, a PTH-related peptide analog, are at present in advanced stages of clinical evaluation, so far demonstrating efficaciousness together with a favorable safety profile. Several other agents are currently in earlier clinical and preclinical phases of development, including dickkopf-1 antagonists, activin A antagonists, β-arrestin analogs, calcilytics, and Src tyrosine kinase inhibitors.

  11. Epidemiological burden of postmenopausal osteoporosis in Italy from 2010 to 2020: estimations from a disease model. (United States)

    Piscitelli, P; Brandi, M; Cawston, H; Gauthier, A; Kanis, J A; Compston, J; Borgström, F; Cooper, C; McCloskey, E


    The article describes the adaptation of a model to estimate the burden of postmenopausal osteoporosis in women aged 50 years and over in Italy between 2010 and 2020. For this purpose, a validated postmenopausal osteoporosis disease model developed for Sweden was adapted to Italy. For each year of the study, the 'incident cohort' (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures and deaths. Fracture by site (hip, clinical vertebral, non-hip non-vertebral) was tracked for each health state. Transition probabilities reflected fracture site-specific risk of death and subsequent fractures. Model inputs specific to Italy included population size and life tables from 1970 to 2020, incidence of hip fracture and BMD by age in the general population (mean and standard deviation). The model estimated that the number of postmenopausal osteoporotic women would increase from 3.3 million to 3.7 million between 2010 and 2020 (+14.3%). Assuming unchanged incidence rates by age group over time, the model predicted the overall number of osteoporotic fractures to increase from 285.0 to 335.8 thousand fractures between 2010 and 2020 (+17.8%). The estimated expected increases in hip, vertebral and non-hip non-vertebral fractures were 22.3, 17.2 and 16.3%, respectively. Due to demographic changes, the burden of fractures is expected to increase markedly by 2020.

  12. Cryptococcus neoformans capsular enlargement and cellular gigantism during Galleria mellonella infection.

    Directory of Open Access Journals (Sweden)

    Rocío García-Rodas

    Full Text Available We have studied infection of Cryptococcus neoformans in the non-vertebrate host Galleria mellonella with particular interest in the morphological response of the yeast. Inoculation of C. neoformans in caterpillars induced a capsule-independent increase in haemocyte density 2 h after infection. C. neoformans manifested a significant increase in capsule size after inoculation into the caterpillar. The magnitude of capsule increase depended on the temperature, being more pronounced at 37°C than at 30°C, which correlated with an increased virulence of the fungus and reduced phagocytosis at 37°C. Capsule enlargement impaired phagocytosis by haemocytes. Incubation of the yeast in G. mellonella extracts also resulted in capsule enlargement, with the polar lipidic fraction having a prominent role in this effect. During infection, the capsule decreased in permeability. A low proportion of the cells (<5% recovered from caterpillars measured more than 30 µm and were considered giant cells. Giant cells recovered from mice were able to kill the caterpillars in a manner similar to regular cells obtained from in vivo or grown in vitro, establishing their capacity to cause disease. Our results indicate that the morphological transitions exhibited by C. neoformans in mammals also occur in a non-vertebrate host system. The similarities in morphological transitions observed in different animal hosts and in their triggers are consistent with the hypothesis that the cell body and capsular responses represent an adaptation of environmental survival strategies to pathogenesis.

  13. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens. (United States)

    López Hernández, Yamilé; Yero, Daniel; Pinos-Rodríguez, Juan M; Gibert, Isidre


    Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host-pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host-pathogen interactions.

  14. Clinical Practice. Postmenopausal Osteoporosis. (United States)

    Black, Dennis M; Rosen, Clifford J


    Key Clinical Points Postmenopausal Osteoporosis Fractures and osteoporosis are common, particularly among older women, and hip fractures can be devastating. Treatment is generally recommended in postmenopausal women who have a bone mineral density T score of -2.5 or less, a history of spine or hip fracture, or a Fracture Risk Assessment Tool (FRAX) score indicating increased fracture risk. Bisphosphonates (generic) and denosumab reduce the risk of hip, nonvertebral, and vertebral fractures; bisphosphonates are commonly used as first-line treatment in women who do not have contraindications. Teriparatide reduces the risk of nonvertebral and vertebral fractures. Osteonecrosis of the jaw and atypical femur fractures have been reported with treatment but are rare. The benefit-to-risk ratio for osteoporosis treatment is strongly positive for most women with osteoporosis. Because benefits are retained after discontinuation of alendronate or zoledronic acid, drug holidays after 5 years of alendronate therapy or 3 years of zoledronic acid therapy may be considered for patients at lower risk for fracture.

  15. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Yamilé eLópez Hernández


    Full Text Available Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as a valuate tools to explore host-pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio, and non-vertebrate insects and nematodes (e.g. Caenorhabditis elegans in the study of diverse infectious agents that affect humans. Here we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favour of the use of these alternative animal models of infection to reveal the molecular signatures of host-pathogen interactions.

  16. [Selective Estrogen Receptor Modulators (SERMs) for prevention and treatment of postmenopausal osteoporosis]. (United States)

    Birkhäuser, Martin


    The three modern Selective Estrogen Receptor Modulators (SERMs) Raloxifene, Lasoxifene and Bazedoxifene registered in Europe reduce in postmenopausal women with a high risk for osteoporosis the incidence of vertebral fractures by 30 - 50 %, depending on the subgroup they belong to. Solid prospective fracture data for risk reduction in non-vertebral fractures, including the hip, are missing for Raloxifene and Bazedoxifene. However, a post hoc analysis suggests that the risk for non-vertebral fractures is significantly reduced by Raloxfene in women with severe osteoporosis. The simultaneous decrease of the incidence of ER-positive invasive breast cancer in Raloxifene users is highly relevant for clinicians. Unfortunately, Raloxifene and Bazedoxifene are, in the EU and in Switzerland, only labelled for the use in the prevention and treatment of postmenopausal osteoporosis. SERMs may induce or augment vasomotor symptoms. Therefore, SERMs are not a first line therapy in early postmenopause. Looking at other hormonal options, Hormone Replacement Therapy (HRT) remains the first line therapy for fracture reduction in the peri- and early postmenopause. SERMs are an appropriate choice for the continuation of fracture prevention after an initial HRT, particularly for the prevention of vertebral fractures. SERMs are safe if (as in oral HRT) the slightly increased risk for venous thrombo-embolism is respected. In conclusion, SERMs have today their well established place in the prevention and treatment of postmenopausal osteoporosis, particularly in women with a simultaneously increased breast cancer risk.

  17. Ascidian introductions through the Suez Canal: The case study of an Indo-Pacific species. (United States)

    Rius, Marc; Shenkar, Noa


    Although marine biological invasions via the Suez Canal have been extensively documented, little is known about the introduction of non-indigenous ascidians (Chordata, Ascidiacea), a group containing particularly aggressive invasive species. Here, we used a multidisciplinary approach to study the introduction of the ascidian Herdmania momus into the Mediterranean Sea. We reviewed its taxonomy and global distribution, and analyzed how genetic variation is partitioned between sides of the Suez Canal. The taxonomic revision showed that H. momus currently has a wide Indo-Pacific distribution. Genetic data indicated two well-differentiated colonization histories across the eastern Mediterranean. Our findings suggest that the range expansion of H. momus has been greatly facilitated by the combined effect of human-mediated transport and the species' ability to adapt to different environments. The integrative approach presented here is critical to attain a holistic understanding of marine biological invasions, especially when studying groups with a poorly resolved taxonomy.

  18. [Morphofunctional organization of reserve stem cells providing for asexual and sexual reproduction of invertebrates]. (United States)

    Isaeva, V V; Akhmadieva, A V; Aleksandriova, Ia N; Shukaliuk, A I


    Published and original data indicating evolutionary conservation of the morphofunctional organization of reserve stem cells providing for asexual and sexual reproduction of invertebrates are reviewed. Stem cells were studied in representatives of five animal types: archeocytes in sponge Oscarella malakhovi (Porifera), large interstitial cells in colonial hydroid Obelia longissima (Cnidaria), neoblasts in an asexual race of planarian Girardia tigrina (Platyhelmintes), stem cells in colonial rhizocephalans Peltogasterella gracilis, Polyascus polygenea, and Thylacoplethus isaevae (Arthropoda), and colonial ascidian Botryllus tuberatus (Chordata). Stem cells in animals of such diverse taxa feature the presence of germinal granules, are positive for proliferating cell nuclear antigen, demonstrate alkaline phosphatase activity (at marker of embryonic stem cells and primary germ cells in vertebrates), and rhizocephalan stem cells express the vasa-like gene (such genes are expressed in germline cells of different metazoans). The self-renewing pool of stem cells is the cellular basis of the reproductive strategy including sexual and asexual reproduction.

  19. 中国鸟类科学研究与保护进展

    Institute of Scientific and Technical Information of China (English)



    鸟类是具有羽毛的恒温动物,在分类上属于动物界脊索动物门(Phylum Chordata)鸟纲(Ayes),全世界共有9700余种。作为野生动物的一个重要类群,鸟类不仅在科学研究上具有很高价值,而且在美化环境、维持生态平系统的平衡与稳定方面发挥重要作用。我国地处古北界和东洋界两大动物地理区,辽阔的疆域和复

  20. Large-scale recoding of an arbovirus genome to rebalance its insect versus mammalian preference. (United States)

    Shen, Sam H; Stauft, Charles B; Gorbatsevych, Oleksandr; Song, Yutong; Ward, Charles B; Yurovsky, Alisa; Mueller, Steffen; Futcher, Bruce; Wimmer, Eckard


    The protein synthesis machineries of two distinct phyla of the Animal kingdom, insects of Arthropoda and mammals of Chordata, have different preferences for how to best encode proteins. Nevertheless, arboviruses (arthropod-borne viruses) are capable of infecting both mammals and insects just like arboviruses that use insect vectors to infect plants. These organisms have evolved carefully balanced genomes that can efficiently use the translational machineries of different phyla, even if the phyla belong to different kingdoms. Using dengue virus as an example, we have undone the genome encoding balance and specifically shifted the encoding preference away from mammals. These mammalian-attenuated viruses grow to high titers in insect cells but low titers in mammalian cells, have dramatically increased LD50s in newborn mice, and induce high levels of protective antibodies. Recoded arboviruses with a bias toward phylum-specific expression could form the basis of a new generation of live attenuated vaccine candidates.

  1. Norepinephrine and octopamine: linking stress and immune function across phyla

    Directory of Open Access Journals (Sweden)

    SA Adamo


    Full Text Available In species from three widely divergent phyla (Arthropoda, Mollusca and Chordata tyrosine derivatives (norepinephrine or octopamine mediate a response to acute stress. Part of this response is a change in immune function that results in a decrease in resistance to pathogens. This decrease in disease resistance appears maladaptive. However, if the connections between norepinephrine/octopamine and immune function were maladaptive, they should have been selected against. None of the four commonly proposed adaptive explanations for acute stress-induced changes in immune function fit the available data for species from all three phyla. However, this result is probably due to the lack of information about acute stress-induced immunosuppression in invertebrates and a lack of ecologically valid studies in vertebrates. Understanding why immune function and disease resistance changes during acute stress will require greater comparative study.

  2. Conservation and diversification of Msx protein in metazoan evolution. (United States)

    Takahashi, Hirokazu; Kamiya, Akiko; Ishiguro, Akira; Suzuki, Atsushi C; Saitou, Naruya; Toyoda, Atsushi; Aruga, Jun


    Msx (/msh) family genes encode homeodomain (HD) proteins that control ontogeny in many animal species. We compared the structures of Msx genes from a wide range of Metazoa (Porifera, Cnidaria, Nematoda, Arthropoda, Tardigrada, Platyhelminthes, Mollusca, Brachiopoda, Annelida, Echiura, Echinodermata, Hemichordata, and Chordata) to gain an understanding of the role of these genes in phylogeny. Exon-intron boundary analysis suggested that the position of the intron located N-terminally to the HDs was widely conserved in all the genes examined, including those of cnidarians. Amino acid (aa) sequence comparison revealed 3 new evolutionarily conserved domains, as well as very strong conservation of the HDs. Two of the three domains were associated with Groucho-like protein binding in both a vertebrate and a cnidarian Msx homolog, suggesting that the interaction between Groucho-like proteins and Msx proteins was established in eumetazoan ancestors. Pairwise comparison among the collected HDs and their C-flanking aa sequences revealed that the degree of sequence conservation varied depending on the animal taxa from which the sequences were derived. Highly conserved Msx genes were identified in the Vertebrata, Cephalochordata, Hemichordata, Echinodermata, Mollusca, Brachiopoda, and Anthozoa. The wide distribution of the conserved sequences in the animal phylogenetic tree suggested that metazoan ancestors had already acquired a set of conserved domains of the current Msx family genes. Interestingly, although strongly conserved sequences were recovered from the Vertebrata, Cephalochordata, and Anthozoa, the sequences from the Urochordata and Hydrozoa showed weak conservation. Because the Vertebrata-Cephalochordata-Urochordata and Anthozoa-Hydrozoa represent sister groups in the Chordata and Cnidaria, respectively, Msx sequence diversification may have occurred differentially in the course of evolution. We speculate that selective loss of the conserved domains in Msx family

  3. Post larval, short-term, colonization patterns: The effect of substratum complexity across subtidal, adjacent, habitats (United States)

    García-Sanz, Sara; Tuya, Fernando; Navarro, Pablo G.; Angulo-Preckler, Carlos; Haroun, Ricardo J.


    Benthic habitats are colonized by organisms from the water column and adjacent habitats. There are, however, variations in the 'acceptability' of any habitat to potential colonists. We assessed whether the structural complexity of artificial substrata affected patterns of short-term colonization of post larval faunal assemblages across subtidal habitats within a coastal landscape. Specifically, we tested whether short-term colonization patterns on 3 types of artificial substrata encompassing a range of complexities, including a leaf-like unit, a cushion-shaped leaf-like unit and a cushion-shaped unit, were consistent across 4 adjacent habitats: macroalgal-dominated bottoms, urchin-grazed barrens, seagrass meadows and sandy patches, at Gran Canaria (eastern Atlantic). A total of 16,174 organisms were collected after 4 weeks and 4 taxonomic groups (Crustacea, Chordata, Echinodermata and Mollusca) dominated the assemblage. Despite considerable among-taxa variability being observed in response to habitat effects, the total abundance of colonizers, as well as the abundance of Arthropoda, Chordata and Echinodermata, was affected by the habitat where collectors were deployed, but did not differ among types of collectors. Similarly, the assemblage structure of colonizers was mainly affected by the habitat, but not by the type of collector; habitat contributed to explain most variation in the assemblage structure of the four dominant taxonomic groups (from ca. 5.44-19.23%), and obscured, in all cases, variation explained by the type of collector. As a result, the variation in short-term colonization patterns of faunal assemblages into artificial collectors was mostly affected by variation associated with habitats rather than by differences in the structural complexity of collectors. The largest abundances of colonizers, particularly Echinodermata, were found on sandy patches relative to other habitats, suggesting that the 'availability', rather than any particular attribute

  4. Treating postmenopausal osteoporosis in women at increased risk of fracture – critical appraisal of bazedoxifene: a review

    Directory of Open Access Journals (Sweden)

    Peter Vestergaard


    Full Text Available Peter Vestergaard, Susanna vid Streym ThomsenDepartment of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus, DenmarkAbstract: Several categories of drugs to treat osteoporosis exist in the form of bisphosphonates, strontium, parathyroid hormone, and selective estrogen receptor modulators (SERM. Advantages and disadvantages exist for each category as some patients may, for example, not tolerate bisphosphonates for gastrointestinal side effects, and especially in women in whom osteoporosis is frequent, several options for treatment are needed. The objectives of this review were to critically appraise the effects of bazedoxifene on risk of fractures especially in women at high risk of fractures. A systematic literature search was conducted for studies, especially randomized controlled trials with fractures as end-points. Bazedoxifene is a new member of the SERM group. The literature search identified one randomized controlled trial with fractures as end-point. This was a 3-year randomized double-blind placebo controlled trial in which 7492 postmenopausal women aged 55 to 85 years were randomly allocated to 1 bazedoxifene (20 [n = 1886] or 40 [n = 1872] mg/day; 2 raloxifene (60 mg/day, n = 1849; or 3 placebo (n = 1885. The risk of vertebral fractures decreased with both 20 (HR 0.58, 95% CI 0.38 to 0.89 and 40 (HR 0.63, 95% CI 0.42 to 0.96 mg of bazedoxifene per day compared to placebo. There was no reduction in non-vertebral fractures. A subgroup of women with a priori high risk of fractures was identified post hoc. In this subgroup there was a reduction in the risk of non-vertebral fractures with the 20 mg dose of bazedoxifene compared to placebo (HR 0.50, 95% CI 0.28 to 0.90. In the 40 mg bazedoxifene group no significant reduction in non-vertebral fractures was seen in this subgroup (HR 0.70, 95% CI 0.40 to 1.20. In general post-hoc defined subgroup analyses should be interpreted with caution. However, the results indicate that

  5. Low Serum DHEAS Predicts Increased Fracture Risk in Older Men: The MrOS Sweden Study. (United States)

    Ohlsson, Claes; Nethander, Maria; Kindmark, Andreas; Ljunggren, Östen; Lorentzon, Mattias; Rosengren, Björn E; Karlsson, Magnus K; Mellström, Dan; Vandenput, Liesbeth


    The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. DHEAS is considered an inactive precursor, which is converted into androgens and estrogens via local metabolism in peripheral target tissues. The predictive value of serum DHEAS for fracture risk is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEAS levels and incident fractures in a large cohort of older men. Serum DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n = 2568, aged 69 to 81 years). Incident X-ray validated fractures (all, n = 594; non-vertebral major osteoporotic, n = 255; hip, n = 175; clinical vertebral, n = 206) were ascertained during a median follow-up of 10.6 years. DHEAS levels were inversely associated with the risk of any fracture (hazard ratio [HR] per SD decrease = 1.14, 95% confidence interval [CI] 1.05-1.24), non-vertebral major osteoporotic fractures (HR = 1.31, 95% CI 1.16-1.48), and hip fractures (HR = 1.18, 95% CI 1.02-1.37) but not clinical vertebral fractures (HR = 1.09, 95% CI 0.95-1.26) in Cox regression models adjusted for age, body mass index (BMI) and prevalent fractures. Further adjustment for traditional risk factors for fracture, bone mineral density (BMD), and/or physical performance variables as well as serum sex steroid levels only slightly attenuated the associations between serum DHEAS and fracture risk. Similarly, the point estimates were only marginally reduced after adjustment for FRAX estimates with BMD. The inverse association between serum DHEAS and all fractures or major osteoporotic fractures was nonlinear, with a substantial increase in fracture risk (all fractures 22%, major osteoporotic fractures 33%) for those participants with serum DHEAS levels below the median (0.60 μg/mL). In

  6. Histatins: salivary peptides with copper(II)- and zinc(II)-binding motifs: perspectives for biomedical applications. (United States)

    Melino, Sonia; Santone, Celeste; Di Nardo, Paolo; Sarkar, Bibudhendra


    Natural antimicrobial peptides represent a primordial mechanism of immunity in both vertebrate and nonvertebrate organisms. Among them, histatins belong to a family of human salivary metal-binding peptides displaying potent antibacterial, antifungal and wound-healing activities. These properties, along with the ability of histatins to inhibit collagenases and cysteine proteases, have attracted much attention for their potential use in the treatment of several oral diseases. This review critically assesses the studies carried out to date in order to provide a comprehensive and systematic vision of the information accumulated so far. In particular, the relationship between metal-binding and peptide activity is extensively analysed. The review provides important clues for developing possible therapeutic applications of histatins and their synthetic peptide analogues by creating a set of necessary resource materials to support investigators and industries interested in exploiting their unique properties.

  7. The evidence for antiresorptive osteoporosis treatment in the elderly and old

    DEFF Research Database (Denmark)

    Maraldo, M; McMurdo, MET; Vestergaard, P;


    Purpose. – The mean age at diagnosis of osteoporosis is in the late 1960s, and fracture risk and need for fracture prevention rises sharply with increasing age. However, what is the evidence that supports the use of antiresorptive osteoporosis treatments in elderly people? Methods. – This study...... was a meta-analysis and meta-regression of the published literature on the clinical efficacy of antiresorptive therapy in the reduction of fracture risk in elderly (age > 70 years) and old (age > 80 years). A systematic literature search was performed. Studies included were randomised placebo controlled...... trials of post-menopausal women or men where the primary endpoint was vertebral, non-vertebral or hip fracture risk reduction. No papers on fractures in males were published, so BMD as primary endpoint was accepted. Results. – Thirteen studies in women were included. We found increasing vertebral...

  8. Bazedoxifene: a new selective estrogen receptor modulator for postmenopausal osteoporosis. (United States)

    Genant, Harry K


    An ongoing need for safe and effective pharmacological therapies exists for postmenopausal osteoporosis, which imposes a significant burden on both women and the health-care system. Bazedoxifene is a novel selective estrogen receptor modulator with a unique tissue-selectivity profile. In phase 3 clinical trials of nearly 10,000 postmenopausal women, bazedoxifene was shown to significantly reduce the risk of new vertebral fracture versus placebo, with favourable effects on bone mineral density, bone turnover markers and the lipid profile. Moreover, in a subgroup of women at increased risk of fracture, bazedoxifene significantly decreased non-vertebral fracture risk versus both placebo and raloxifene. Bazedoxifene has been shown to be safe and well tolerated, with no evidence of endometrial or breast stimulation. These data suggest that bazedoxifene may offer significant clinical benefit for postmenopausal women with or at risk of developing osteoporosis, which may subsequently lessen the medical and economic burden of this disease.

  9. Effects of Abaloparatide-SC on Fractures and Bone Mineral Density in Subgroups of Postmenopausal Women With Osteoporosis and Varying Baseline Risk Factors. (United States)

    Cosman, Felicia; Hattersley, Gary; Hu, Ming-Yi; Williams, Gregory C; Fitzpatrick, Lorraine A; Black, Dennis M


    Abaloparatide-SC is a novel 34-amino acid peptide created to be a potent and selective activator of the parathyroid hormone receptor type 1 (PTHR1) signaling pathway. In the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) Phase 3 trial (NCT01343004), abaloparatide reduced new morphometric vertebral fractures by 86% compared with placebo (p osteoporosis. Abaloparatide-SC increased bone mineral density (BMD) 3.4% at the total hip, 2.9% at the femoral neck, and 9.2% at the lumbar spine at 18 months (all p -2.5 and ≤-3.0 versus >-3.0), history of nonvertebral fracture (yes versus no), prevalent vertebral fracture (yes versus no), and age (osteoporosis. © 2016 American Society for Bone and Mineral Research.

  10. Efficacy of ibandronate: a long term confirmation. (United States)

    Di Munno, Ombretta; Delle Sedie, Andrea


    Data deriving from randomized clinical trials, observational studies and meta-analyses, including treatment regimens unlicensed for use in clinical practice, clearly support that 150 mg once-monthly oral and 3 mg quarterly i.v. doses of ibandronate are associated with efficacy, safety and tolerability; notably both these marketed regimens, which largely correspond to ACE ≥10.8 mg, may in addition provide a significant efficacy on non-vertebral and clinical fracture (Fx) efficacy. The MOBILE and the DIVA LTE studies confirmed a sustained efficacy of monthly oral and quarterly i.v. regimens respectively, over 5 years. Furthermore, improved adherence rates with monthly ibandronate, deriving from studies evaluating large prescription databases, promise to enhance fracture protection and decrease the social and economic burden of postmenopausal osteoporosis.

  11. Antimicrobial Peptides: Multifunctional Drugs for Different Applications

    Directory of Open Access Journals (Sweden)

    Lea-Jessica Albrecht


    Full Text Available Antimicrobial peptides (APs are an important part of the innate immune system in epithelial and non-epithelial surfaces. So far, many different antimicrobial peptides from various families have been discovered in non-vertebrates and vertebrates. They are characterized by antibiotic, antifungal and antiviral activities against a variety of microorganisms. In addition to their role as endogenous antimicrobials, APs participate in multiple aspects of immunity. They are involved in septic and non-septic inflammation, wound repair, angiogenesis, regulation of the adaptive immune system and in maintaining homeostasis. Due to those characteristics AP could play an important role in many practical applications. Limited therapeutic efficiency of current antimicrobial agents and the emerging resistance of pathogens require alternate antimicrobial drugs. The purpose of this review is to highlight recent literature on functions and mechanisms of APs. It also shows their current practical applications as peptide therapeutics and bioactive polymers and discusses the possibilities of future clinical developments.

  12. Discontinuation of denosumab and associated fracture incidence

    DEFF Research Database (Denmark)

    Brown, Jacques P; Roux, Christian; Törring, Ove;


    Osteoporosis is a chronic disease and requires long-term treatment with pharmacologic therapy to ensure sustained anti-fracture benefit. Denosumab reduced the risk for new vertebral, nonvertebral, and hip fractures over 36 months in the FREEDOM trial. While discontinuation of denosumab has been...... associated with transient increases in bone remodeling and declines in bone mineral density (BMD), the effect on fracture risk during treatment cessation is not as well characterized. To understand the fracture incidence between treatment groups after cessation of investigational product, we evaluated...... of 797 subjects (470 placebo, 327 denosumab), who were evaluable during the off-treatment period, showed similar baseline characteristics for age, prevalent fracture, and lumbar spine and total hip BMD T-scores. During treatment, more placebo-treated subjects as compared with denosumab-treated subjects...

  13. Hemozoin formation in Echinostoma trivolvis rediae. (United States)

    Pisciotta, John M; Ponder, Elizabeth L; Fried, Bernard; Sullivan, David


    Rediae of the trematode Echinostoma trivolvis, from naturally infected Helisoma trivolvis snails, form a black pigment while inside the snail host. Here we examine the black pigment to show that the insolubility characteristics in detergent and weak base solution are identical to Plasmodium falciparum hemozoin. Laser desorption mass spectrometry of the purified pigment demonstrates the presence of heme. Examination of purified pigment under polarized light microscopy illuminates ordered birefringent crystals. Field emission in lens scanning electron microscopy reveals irregular ovoid crystals of 200-300 nm in diameter. The purified pigment crystals seeded extension of monomeric heme onto the crystal which by Fourier Transform Infrared analysis is beta-hematin. Rediae of a second echinostome parasite, Echinostoma caproni, from experimentally infected Biomphalaria glabrata, do not produce measurable or recoverable heme crystals. These observations are consistent with heme crystal formation by a hematophagous parasite within a non-vertebrate intermediate host.

  14. Musculoskeletal Challenges of Osteoporosis:Therapeutic Exercise/Strength Training A Review - Review

    Directory of Open Access Journals (Sweden)

    Mehrsheed Sinaki


    Full Text Available Combining pharmacotherapy with non-pharmacotherapy is fundamental to the successful management of osteopenia and osteoporosis. The choice of pharmacotherapy depends on the patient’s age, bone mineral density and serum biochemical markers of bone. HRT should not be used for treatment of osteoporosis. As with pharmacotherapy, rehabilitation management is challenging and innovative. Non-pathologic spontaneous vertebral fractures that occur at the level of the spine are purely osteoporosis-related. On the other hand, the majority of non-vertebral fractures that are of special clinical significance are fall-related. Therefore, reducing the risk for fracture through the prevention of falls is as important as increasing bone mass. (From the World of Osteoporosis 2009;15:52-8

  15. Raloxifene: Mechanism of Action, Effects on Bone Tissue, and Applicability in Clinical Traumatology Practice (United States)

    Rey, Jose R. Caeiro; Cervino, Eduardo Vaquero; Rentero, Maria Luz; Crespo, Emilio Calvo; Álvaro, Angel Oteo; Casillas, Marta


    Raloxifene, a member of the class of selective estrogen receptor modulators (SERM), reproduces the beneficial effects of estrogens on the skeletal systems, without the negative effects estrogens on breast and endometrium. This is a review article summarizing its mechanism, effects on bone and its applicability in traumatology clinical practice. In postmenopausal osteoporosis, this drug has been proven to decrease accelerated bone turnover, increase bone mineral density (BMD), and to structurally recover bone, decreasing the risk of vertebral fractures and the risk of non-vertebral fractures in patients with previous, severe vertebral fractures. Moreover, raloxifene appears to lower the risk of invasive breast cancer. Raloxifene would be efficacious in the prevention and treatment of postmenopausal osteoporosis. We can therefore conclude that raloxifene would be efficacious in the prevention and treatment of postmenopausal osteoporosis, while reducing the risk of breast cancer when used at the indicated dose of 60 mg/day and with a low incidence of side effects. PMID:19516920

  16. Bazedoxifene: a novel selective estrogen receptor modulator for postmenopausal osteoporosis. (United States)

    de Villiers, T J


    Several new selective estrogen receptor modulators (SERMs) are currently under clinical development for the prevention and/or treatment of postmenopausal osteoporosis, with the goal of optimizing the estrogen receptor agonist/antagonist activity in target tissues. Bazedoxifene is a novel SERM under clinical investigation for the prevention and treatment of postmenopausal osteoporosis. Emerging clinical data have shown that bazedoxifene is effective in preventing bone loss and osteoporotic fractures in postmenopausal women, with no evidence of breast or endometrial stimulation. Two large, prospective, international phase 3 studies have been completed. In postmenopausal women at risk for osteoporosis, bazedoxifene has been shown to preserve bone mineral density and to reduce bone turnover. In postmenopausal women with osteoporosis, bazedoxifene has demonstrated significant protection against new vertebral fractures and against non-vertebral fractures in women at higher fracture risk. The treatment effects of bazedoxifene were supported by findings from independent re-analyses using the Fracture Risk Assessment Tool (FRAX), which showed that bazedoxifene significantly reduced the risk of all clinical and morphometric vertebral fracture and of non-vertebral fracture in women at or above a FRAX-based threshold. Bazedoxifene was generally safe and well tolerated in the phase 3 studies and showed neutral effects on the breast and an excellent endometrial safety profile; such attributes allow for the partnering of bazedoxifene with conjugated estrogens for menopausal symptom relief. Collectively, these results suggest that bazedoxifene may be a promising new therapy for the prevention and treatment of postmenopausal osteoporosis as a monotherapy or in combination with conjugated estrogens in menopausal hormone therapy.

  17. Does Alendronate reduce the risk of fracture in men? A meta-analysis incorporating prior knowledge of anti-fracture efficacy in women

    Directory of Open Access Journals (Sweden)

    Papaioannou Alexandra


    Full Text Available Abstract Background Alendronate has been found to reduce the risk of fractures in postmenopausal women as demonstrated in multiple randomized controlled trials enrolling thousands of women. Yet there is a paucity of such randomized controlled trials in osteoporotic men. Our objective was to systematically review the anti-fracture efficacy of alendronate in men with low bone mass or with a history of prevalent fracture(s and incorporate prior knowledge of alendronate efficacy in women in the analysis. Methods We examined randomized controlled trials in men comparing the anti-fracture efficacy of alendronate to placebo or calcium or vitamin D, or any combination of these. Studies of men with secondary causes of osteoporosis other than hypogonadism were excluded. We searched the following electronic databases (without language restrictions for potentially relevant citations: Medline, Medline in Process (1966-May 24/2004, and Embase (1996–2004. We also contacted the manufacturer of the drug in search of other relevant trials. Two reviewers independently identified two trials (including 375 men, which met all inclusion criteria. Data were abstracted by one reviewer and checked by another. Results of the male trials were pooled using Bayesian random effects models, incorporating prior information of anti-fracture efficacy from meta-analyses of women. Results The odds ratios of incident fractures in men (with 95% credibility intervals with alendronate (10 mg daily were: vertebral fractures, 0.44 (0.23, 0.83 and non-vertebral fractures, 0.60 (0.29, 1.44. Conclusion In conclusion, alendronate decreases the risk of vertebral fractures in men at risk. There is currently insufficient evidence of a statistically significant reduction of non-vertebral fractures, but the paucity of trials in men limit the statistical power to detect such an effect.

  18. Cost-effectiveness of preventative therapies for postmenopausal women with osteopenia

    Directory of Open Access Journals (Sweden)

    Smolen Lee


    Full Text Available Abstract Background Limited data are available regarding the cost-effectiveness of preventative therapies for postmenopausal women with osteopenia. The objective of the present study was to evaluate the cost-effectiveness of raloxifene, alendronate and conservative care in this population. Methods We developed a microsimulation model to assess the incremental cost and effectiveness of raloxifene and alendronate relative to conservative care. We assumed a societal perspective and a lifetime time horizon. We examined clinical scenarios involving postmenopausal women from 55 to 75 years of age with bone mineral density T-scores ranging from -1.0 to -2.4. Modeled health events included vertebral and nonvertebral fractures, invasive breast cancer, and venous thromboembolism (VTE. Raloxifene and alendronate were assumed to reduce the incidence of vertebral but not nonvertebral fractures; raloxifene was assumed to decrease the incidence of breast cancer and increase the incidence of VTEs. Cost-effectiveness is reported in $/QALYs gained. Results For women 55 to 60 years of age with a T-score of -1.8, raloxifene cost approximately $50,000/QALY gained relative to conservative care. Raloxifene was less cost-effective for women 65 and older. At all ages, alendronate was both more expensive and less effective than raloxifene. In most clinical scenarios, raloxifene conferred a greater benefit (in QALYs from prevention of invasive breast cancer than from fracture prevention. Results were most sensitive to the population's underlying risk of fracture and breast cancer, assumed efficacy and costs of treatment, and the discount rate. Conclusion For 55 and 60 year old women with osteopenia, treatment with raloxifene compares favorably to interventions accepted as cost-effective.

  19. Urochordate ascidians possess a single isoform of Aurora kinase that localizes to the midbody via TPX2 in eggs and cleavage stage embryos.

    Directory of Open Access Journals (Sweden)

    Celine Hebras

    Full Text Available Aurora kinases are key proteins found throughout the eukaryotes that control mitotic progression. Vertebrate Aurora-A and B kinases are thought to have evolved from a single Aurora-kinase isoform closest to that found in present day urochordates. In urochordate ascidians Aurora binds both TPX2 (a vertebrate AURKA partner and INCENP (a vertebrate AURKB partner and localizes to centrosomes and spindle microtubules as well as chromosomes and midbody during both meiosis and mitosis. Ascidian Aurora also displays this localization pattern during mitosis in echinoderms, strengthening the idea that non-vertebrate deuterostomes such as the urochordates and echinoderms possess a single form of Aurora kinase that has properties of vertebrate Aurora-kinase A and B. In the ascidian, TPX2 localizes to the centrosome and the spindle poles also as in vertebrates. However, we were surprised to find that TPX2 also localized strongly to the midbody in ascidian eggs and embryos. We thus examined more closely Aurora localization to the midbody by creating two separate point mutations of ascidian Aurora predicted to perturb binding to TPX2. Both forms of mutated Aurora behaved as predicted: neither localized to spindle poles where TPX2 is enriched. Interestingly, neither form of mutated Aurora localized to the midbody where TPX2 is also enriched, suggesting that ascidian Aurora midbody localization required TPX2 binding in ascidians. Functional analysis revealed that inhibition of Aurora kinase with a pharmacological inhibitor or with a dominant negative kinase dead form of Aurora caused cytokinesis failure and perturbed midbody formation during polar body extrusion. Our data support the view that vertebrate Aurora-A and B kinases evolved from a single non-vertebrate deuterostome ancestor. Moreover, since TPX2 localizes to the midbody in ascidian eggs and cleavage stage embryos it may be worthwhile re-assessing whether Aurora A kinase or TPX2 localize to the midbody

  20. Structure of the red fluorescent protein from a lancelet (Branchiostoma lanceolatum): a novel GYG chromophore covalently bound to a nearby tyrosine

    Energy Technology Data Exchange (ETDEWEB)

    Pletnev, Vladimir Z., E-mail:; Pletneva, Nadya V.; Lukyanov, Konstantin A.; Souslova, Ekaterina A.; Fradkov, Arkady F.; Chudakov, Dmitry M.; Chepurnykh, Tatyana; Yampolsky, Ilia V. [Russian Academy of Sciences, Moscow (Russian Federation); Wlodawer, Alexander [National Cancer Institute, Frederick, MD 21702 (United States); Dauter, Zbigniew [National Cancer Institute, Argonne, IL 60439 (United States); Pletnev, Sergei, E-mail: [National Cancer Institute, Argonne, IL 60439 (United States); SAIC-Frederick, Argonne, IL 60439 (United States); Russian Academy of Sciences, Moscow (Russian Federation)


    The crystal structure of the novel red emitting fluorescent protein from lancelet Branchiostoma lanceolatum (Chordata) revealed an unusual five residues cyclic unit comprising Gly58-Tyr59-Gly60 chromophore, the following Phe61 and Tyr62 covalently bound to chromophore Tyr59. A key property of proteins of the green fluorescent protein (GFP) family is their ability to form a chromophore group by post-translational modifications of internal amino acids, e.g. Ser65-Tyr66-Gly67 in GFP from the jellyfish Aequorea victoria (Cnidaria). Numerous structural studies have demonstrated that the green GFP-like chromophore represents the ‘core’ structure, which can be extended in red-shifted proteins owing to modifications of the protein backbone at the first chromophore-forming position. Here, the three-dimensional structures of green laGFP (λ{sub ex}/λ{sub em} = 502/511 nm) and red laRFP (λ{sub ex}/λ{sub em} ≃ 521/592 nm), which are fluorescent proteins (FPs) from the lancelet Branchiostoma lanceolatum (Chordata), were determined together with the structure of a red variant laRFP-ΔS83 (deletion of Ser83) with improved folding. Lancelet FPs are evolutionarily distant and share only ∼20% sequence identity with cnidarian FPs, which have been extensively characterized and widely used as genetically encoded probes. The structure of red-emitting laRFP revealed three exceptional features that have not been observed in wild-type fluorescent proteins from Cnidaria reported to date: (i) an unusual chromophore-forming sequence Gly58-Tyr59-Gly60, (ii) the presence of Gln211 at the position of the conserved catalytic Glu (Glu222 in Aequorea GFP), which proved to be crucial for chromophore formation, and (iii) the absence of modifications typical of known red chromophores and the presence of an extremely unusual covalent bond between the Tyr59 C{sup β} atom and the hydroxyl of the proximal Tyr62. The impact of this covalent bond on the red emission and the large Stokes shift (

  1. Conodonts, Calcichordates and the Origin of Vertebrates

    Directory of Open Access Journals (Sweden)

    J. Bergström


    Echinodermen-ähnlichen Kalzitskeletten als “calcichordate” Vorfahren der Chordata setzt jedoch die hypothetische Rekonstruktion eines ungewöhnlichen Bauplans sowie eine lange Serie hypothetischer Übergänge voraus. Die Anzahl der notwendigen Schritte ist sehr viel geringer. wenn Cephalochordaten (Amphioxus oder das Lanzettfischchen von hemichordaten Enteropneusta abgeleitet werden. Zusätzliche Verwirrung hat es durch sensationelle Interpretationen von Fossilien, Wie Yunnanozoon und Cathaymyrus aus Burgess-Schiefer-artigen Ablagerungen gegeben. Weichkörpererhaltung von Conodontentieren, die V-förmige Myomere sowie einen Notochord besitzen, zeigen, daß es sich um segmentierte Chordata handelte, während sie die Präsenz möglicher Augenstrukturen und Zähne bereits auf die Seite der Vertebraten stellt. doi:10.1002/mmng.19980010106

  2. Perturbing A-to-I RNA editing using genetics and homologous recombination. (United States)

    Staber, Cynthia J; Gell, Selena; Jepson, James E C; Reenan, Robert A


    Evidence for the chemical conversion of adenosine-to-inosine (A-to-I) in messenger RNA (mRNA) has been detected in numerous metazoans, especially those "most successful" phyla: Arthropoda, Mollusca, and Chordata. The requisite enzymes for A-to-I editing, ADARs (adenosine deaminases acting on RNA) are highly conserved and are present in every higher metazoan genome sequenced to date. The fruit fly, Drosophila melanogaster, represents an ideal model organism for studying A-to-I editing, both in terms of fundamental biochemistry and in relation to determining adaptive downstream effects on physiology and behavior. The Drosophila genome contains a single structural gene for ADAR (dAdar), yet the fruit fly transcriptome has the widest range of conserved and validated ADAR targets in coding mRNAs of any known organism. In addition, many of the genes targeted by dADAR have been genetically identified as playing a role in nervous system function, providing a rich source of material to investigate the biological relevance of this intriguing process. Here, we discuss how recent advances in the use of ends-out homologous recombination (HR) in Drosophila make possible both the precise control of the editing status for defined adenosine residues and the engineering of flies with globally altered RNA editing of the fly transcriptome. These new approaches promise to significantly improve our understanding of how mRNA modification contributes to insect physiology and ethology.

  3. Improvement of molecular phylogenetic inference and the phylogeny of Bilateria. (United States)

    Lartillot, Nicolas; Philippe, Hervé


    Inferring the relationships among Bilateria has been an active and controversial research area since Haeckel. The lack of a sufficient number of phylogenetically reliable characters was the main limitation of traditional phylogenies based on morphology. With the advent of molecular data, this problem has been replaced by another one, statistical inconsistency, which stems from an erroneous interpretation of convergences induced by multiple changes. The analysis of alignments rich in both genes and species, combined with a probabilistic method (maximum likelihood or Bayesian) using sophisticated models of sequence evolution, should alleviate these two major limitations. We applied this approach to a dataset of 94 genes and 79 species using CAT, a previously developed model accounting for site-specific amino acid replacement patterns. The resulting tree is in good agreement with current knowledge: the monophyly of most major groups (e.g. Chordata, Arthropoda, Lophotrochozoa, Ecdysozoa, Protostomia) was recovered with high support. Two results are surprising and are discussed in an evo-devo framework: the sister-group relationship of Platyhelminthes and Annelida to the exclusion of Mollusca, contradicting the Neotrochozoa hypothesis, and, with a lower statistical support, the paraphyly of Deuterostomia. These results, in particular the status of deuterostomes, need further confirmation, both through increased taxonomic sampling, and future improvements of probabilistic models.

  4. Structural analysis of the bright monomeric yellow-green fluorescent protein mNeonGreen obtained by directed evolution. (United States)

    Clavel, Damien; Gotthard, Guillaume; von Stetten, David; De Sanctis, Daniele; Pasquier, Hélène; Lambert, Gerard G; Shaner, Nathan C; Royant, Antoine


    Until recently, genes coding for homologues of the autofluorescent protein GFP had only been identified in marine organisms from the phyla Cnidaria and Arthropoda. New fluorescent-protein genes have now been found in the phylum Chordata, coding for particularly bright oligomeric fluorescent proteins such as the tetrameric yellow fluorescent protein lanYFP from Branchiostoma lanceolatum. A successful monomerization attempt led to the development of the bright yellow-green fluorescent protein mNeonGreen. The structures of lanYFP and mNeonGreen have been determined and compared in order to rationalize the directed evolution process leading from a bright, tetrameric to a still bright, monomeric fluorescent protein. An unusual discolouration of crystals of mNeonGreen was observed after X-ray data collection, which was investigated using a combination of X-ray crystallography and UV-visible absorption and Raman spectroscopies, revealing the effects of specific radiation damage in the chromophore cavity. It is shown that X-rays rapidly lead to the protonation of the phenolate O atom of the chromophore and to the loss of its planarity at the methylene bridge.

  5. Back to solitude: Solving the phylogenetic position of the Diazonidae using molecular and developmental characters. (United States)

    Shenkar, Noa; Koplovitz, Gil; Dray, Liran; Gissi, Carmela; Huchon, Dorothée


    The order Aplousobranchia (Chordata, Ascidiacea) contains approximately 1500 species distributed worldwide. Their phylogeny, however, remains unclear, with unresolved family relationships. While most Aplousobranchia are colonial, debates exist concerning the phylogenetic position of families such as the Diazonidae and Cionidae, which exhibit a solitary lifestyle and share morphological characteristics with both Aplousobranchia and Phlebobranchia orders. To clarify the phylogenetic position of the Diazonidae and Cionidae, we determined the complete mitochondrial sequence of the solitary diazonid Rhopalaea idoneta. The phylogenetic reconstruction based on the 13 mitochondrial protein coding genes strongly supports a positioning of Diazonidae well-nested within the Aplousobranchia rather than a positioning as a sister clade of the Aplousobranchia. In addition, we examined the regenerative ability of R. idoneta. Similar to colonial Aplousobranchia, R. idoneta was found to be able to completely regenerate its thorax. Ciona, also known to possess high regenerative abilities, is the Aplousobranchia sister clade rather than a member of the Phlebobranchia. Our results thus indicate that the colonial lifestyle was acquired in the Aplousobranchia, starting from a Ciona-like solitary ancestor and secondarily lost in Diazonidae representatives such as Rhopalaea. The solitary lifestyle of Rhopalaea is thus a derived characteristic rather than an ancestral trait.

  6. Tidal effects on short-term mesozooplankton distribution in small channels of a temperate-turbid estuary, Southwestern Atlantic

    Directory of Open Access Journals (Sweden)

    Javier Chazarreta


    Full Text Available Abstract The short-term variability of mesozooplankton distribution and physicochemical variables was examined in two different channels of the Bahía Blanca Estuary, Argentina, during two tidal cycles. All the physicochemical measurements and mesozooplankton sampling were performed at a fixed site during approximately 22-23 h at 3-h intervals. Pumps were used to obtain surface and bottom mesozooplankton samples and the water speed of each stratum was measured with an Acoustic Doppler Current Profiler (ADCP. In all, 23 mesozooplanktonic taxa belonging to four phyla (Arthropoda, Annelida, Echinodermata and Chordata were identified. The most abundant taxa during the two tidal cycles were Balanus glandula larvae, Eurytemora americana and Acartia tonsa. A discernible variability in the water conditions and vertical mesozooplankton distribution (VMD different from that known for the estuary's main channel, was found in the other two selected channels. VMD varied during the tidal cycle in both channels in accordance with the channel's geomorphology and water dynamic characteristics of each of them. The variation of the abundance of the different taxa during ebb and flood currents might indicate the existence of a tidal vertical migration of the mesozooplankton as a response to particular dynamic water conditions.

  7. Carotenoid metabolic profiling and transcriptome-genome mining reveal functional equivalence among blue-pigmented copepods and appendicularia

    KAUST Repository

    Mojib, Nazia


    The tropical oligotrophic oceanic areas are characterized by high water transparency and annual solar radiation. Under these conditions, a large number of phylogenetically diverse mesozooplankton species living in the surface waters (neuston) are found to be blue pigmented. In the present study, we focused on understanding the metabolic and genetic basis of the observed blue phenotype functional equivalence between the blue-pigmented organisms from the phylum Arthropoda, subclass Copepoda (Acartia fossae) and the phylum Chordata, class Appendicularia (Oikopleura dioica) in the Red Sea. Previous studies have shown that carotenoid–protein complexes are responsible for blue coloration in crustaceans. Therefore, we performed carotenoid metabolic profiling using both targeted and nontargeted (high-resolution mass spectrometry) approaches in four different blue-pigmented genera of copepods and one blue-pigmented species of appendicularia. Astaxanthin was found to be the principal carotenoid in all the species. The pathway analysis showed that all the species can synthesize astaxanthin from β-carotene, ingested from dietary sources, via 3-hydroxyechinenone, canthaxanthin, zeaxanthin, adonirubin or adonixanthin. Further, using de novo assembled transcriptome of blue A. fossae (subclass Copepoda), we identified highly expressed homologous β-carotene hydroxylase enzymes and putative carotenoid-binding proteins responsible for astaxanthin formation and the blue phenotype. In blue O. dioica (class Appendicularia), corresponding putative genes were identified from the reference genome. Collectively, our data provide molecular evidences for the bioconversion and accumulation of blue astaxanthin–protein complexes underpinning the observed ecological functional equivalence and adaptive convergence among neustonic mesozooplankton.

  8. Phylogenetic analysis of uroporphyrinogen III synthase (UROS) gene. (United States)

    Shaik, Abjal Pasha; Alsaeed, Abbas H; Sultana, Asma


    The uroporphyrinogen III synthase (UROS) enzyme (also known as hydroxymethylbilane hydrolyase) catalyzes the cyclization of hydroxymethylbilane to uroporphyrinogen III during heme biosynthesis. A deficiency of this enzyme is associated with the very rare Gunther's disease or congenital erythropoietic porphyria, an autosomal recessive inborn error of metabolism. The current study investigated the possible role of UROS (Homo sapiens [EC:; 265 aa; 1371 bp mRNA; Entrez Pubmed ref NP_000366.1, NM_000375.2]) in evolution by studying the phylogenetic relationship and divergence of this gene using computational methods. The UROS protein sequences from various taxa were retrieved from GenBank database and were compared using Clustal-W (multiple sequence alignment) with defaults and a first-pass phylogenetic tree was built using neighbor-joining method as in DELTA BLAST 2.2.27+ version. A total of 163 BLAST hits were found for the uroporphyrinogen III synthase query sequence and these hits showed putative conserved domain, HemD superfamily (as on 14(th) Nov 2012). We then narrowed down the search by manually deleting the proteins which were not UROS sequences and sequences belonging to phyla other than Chordata were deleted. A repeat phylogenetic analysis of 39 taxa was performed using PhyML and TreeDyn software to confirm that UROS is a highly conserved protein with approximately 85% conserved sequences in almost all chordate taxons emphasizing its importance in heme synthesis.

  9. ELNAIS meets EASIN: distribution of marine alien species in Greece using EASIN mapping services and ELNAIS spatial data

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    Full Text Available The European Alien Species Information Network (EASIN was created with the aim to provide easy access to accurate information on alien species in Europe. EASIN allows the retrieval of spatial information from existing online data providers in order to produce integrated georeferenced distribution maps of alien species in Europe. In November 2012, a new data provider, the Ellenic Network on Aquatic Invasive Species (ELNAIS, joined EASIN; this has significantly increased the available georeferenced information on marine/estuarine alien species in Greek waters. Here, we use maps created by EASIN to show differences in patterns of distribution in Greece for the most abundant Phyla of marine alien species - Mollusca, Arthropoda, Chordata and Annelida. We also show that the two main pathways of introduction of marine alien species (Lessepsian migration and Shipping are related to different patterns of species spatial distribution in Greece. Overall, the tools provided by EASIN can greatly aid scientists and policy makers in obtaining high quality information on marine alien species in Greece, especially after the association with ELNAIS.

  10. Zooplankton diversity across three Red Sea reefs using pyrosequencing

    KAUST Repository

    Pearman, John K.


    Coral reefs are considered among the most diverse ecosystems on Earth, yet little is known about the diversity of plankton in the surrounding water column. Moreover, few studies have utilized genomic methods to investigate zooplankton diversity in any habitat. This study investigated the diversity of taxa by sampling 45 stations around three reef systems in the central/southern Red Sea. The diversity of metazoan plankton was investigated by targeting the 18S rRNA gene and clustering OTUs at 97% sequence similarity. A total of 754 and 854 metazoan OTUs were observed in the data set for the 1380F and 1389F primer sets respectively. The phylum Arthropoda dominated both primer sets accounting for ~60% of reads followed by Cnidaria (~20%). Only about 20% of OTUs were shared between all three reef systems and the relation between geographic distance and Jaccard Similarity measures was not significant. Cluster analysis showed that there was no distinct split between reefs and stations from different reefs clustered together both for metazoans as a whole and for the phyla Arthropoda, Cnidaria and Chordata separately. This suggests that distance may not be a determining factor in the taxonomic composition of stations.

  11. Histamine regulates the inflammatory response of the tunicate Styela plicata. (United States)

    García-García, Erick; Gómez-González, Nuria E; Meseguer, José; García-Ayala, Alfonsa; Mulero, Victoriano


    Histamine is stored inside hemocytes of the tunicate Styela plicata (Chordata, Tunicata, Ascidiacea), but no evidence on its role in the regulation of the immune response of this species has been reported. We examined whether histamine participated in the regulation of inflammation and host defense in S. plicata. The presence of histamine inside S. plicata hemocytes was confirmed by flow cytometry, and histamine release was detected by ELISA, after in vitro hemocyte stimulation with different PAMPs. In vitro hemocyte treatment with histamine, or specific histamine-receptor agonists, reduced their phagocytic ability. Injection of histamine into the tunic recruited hemocytes to the site of injection. Systemic injection of histamine, or the histamine-releasing agent compound 48/80, decreased the phagocytic ability of hemocytes. Histamine promoted the constriction of tunic hemolymph vessels in vivo, having a direct effect on vasoconstriction in tunic explants. These results provide for the first time clear evidence for the involvement of histamine in the regulation of inflammation and host defense in tunicates.

  12. Osmotic/ionic status of body fluids in the euryhaline cephalopod suggest possible parallel evolution of osmoregulation. (United States)

    Sakamoto, Tatsuya; Ogawa, Satoshi; Nishiyama, Yudai; Akada, Chiaki; Takahashi, Hideya; Watanabe, Taro; Minakata, Hiroyuki; Sakamoto, Hirotaka


    Acclimation from marine to dilute environments constitutes among the dramatic evolutionary transitions in the history of life. Such adaptations have evolved in multiple lineages, but studies of the blood/hemolymph homeostasis mechanisms are limited to those using evolutionarily advanced Deuterostome (chordates) and Ecdysozoa (crustaceans). Here, we examined hemolymph homeostasis in the advanced Lophotrochozoa/mollusc, the other unexplored taxa, and its possible regulation by the vasopressin/oxytocin superfamily peptides known to be implicated in fluid homeostasis in Chordata and Arthropoda. The hemolymph osmotic and ionic status in the euryhaline cephalopod (Octopus ocellatus) following transfer from 30-ppt normal seawater to 20 ppt salinity indicate hyperosmo- and hyperionoregulatory abilities for more than 1 week, as in crustaceans and teleost fish. While ventilation frequency decreased by 1 day, Na(+)/K(+)-ATPase activity, which has been generally implicated in ion transport, was induced in two of the eight posterior gills after 1 week. In addition, the octopuses were intravenously injected with 1 or 100 ng/g octopressin or cephalotocin, which are Octopus vasopressin/oxytocin orthologs. After 1 day, octopressin, but not cephalotocin, decreased the hemolymph osmolality and Ca concentrations, as well as urinary Na concentrations. These data provide evidence for possible parallel evolution in hyperionoregulatory mechanisms and coordination by conserved peptides.

  13. EST sequencing of Onychophora and phylogenomic analysis of Metazoa. (United States)

    Roeding, Falko; Hagner-Holler, Silke; Ruhberg, Hilke; Ebersberger, Ingo; von Haeseler, Arndt; Kube, Michael; Reinhardt, Richard; Burmester, Thorsten


    Onychophora (velvet worms) represent a small animal taxon considered to be related to Euarthropoda. We have obtained 1873 5' cDNA sequences (expressed sequence tags, ESTs) from the velvet worm Epiperipatus sp., which were assembled into 833 contigs. BLAST similarity searches revealed that 51.9% of the contigs had matches in the protein databases with expectation values lower than 10(-4). Most ESTs had the best hit with proteins from either Chordata or Arthropoda (approximately 40% respectively). The ESTs included sequences of 27 ribosomal proteins. The orthologous sequences from 28 other species of a broad range of phyla were obtained from the databases, including other EST projects. A concatenated amino acid alignment comprising 5021 positions was constructed, which covers 4259 positions when problematic regions were removed. Bayesian and maximum likelihood methods place Epiperipatus within the monophyletic Ecdysozoa (Onychophora, Arthropoda, Tardigrada and Nematoda), but its exact relation to the Euarthropoda remained unresolved. The "Articulata" concept was not supported. Tardigrada and Nematoda formed a well-supported monophylum, suggesting that Tardigrada are actually Cycloneuralia. In agreement with previous studies, we have demonstrated that random sequencing of cDNAs results in sequence information suitable for phylogenomic approaches to resolve metazoan relationships.

  14. Complete mitochondrial genome sequence of the polychaete annelidPlatynereis dumerilii

    Energy Technology Data Exchange (ETDEWEB)

    Boore, Jeffrey L.


    Complete mitochondrial genome sequences are now available for 126 metazoans (see Boore 1999; Mitochondrial Genomics link at, but the taxonomic representation is highly biased. For example, 80 are from a single phylum, Chordata, and show little variation for many molecular features. Arthropoda is represented by 16 taxa, Mollusca by eight, and Echinodermata by five, with only 17 others from the remaining {approx}30 metazoan phyla. With few exceptions (see Wolstenholme 1992 and Boore 1999) these are circular DNA molecules, about 16 kb in size, and encode the same set of 37 genes. A variety of non-standard names are sometimes used for animal mitochondrial genes; see Boore (1999) for gene nomenclature and a table of synonyms. Mitochondrial genome comparisons serve as a model of genome evolution. In this system, much smaller and simpler than that of the nucleus, are all of the same factors of genome evolution, where one may find tractable the changes in tRNA structure, base composition, genetic code, gene arrangement, etc. Further, patterns of mitochondrial gene rearrangements are an exceptionally reliable indicator of phylogenetic relationships (Smith et al.1993; Boore et al. 1995; Boore, Lavrov, and Brown 1998; Boore and Brown 1998, 2000; Dowton 1999; Stechmann and Schlegel 1999; Kurabayashi and Ueshima 2000). To these ends, we are sampling further the variation among major animal groups in features of their mitochondrial genomes.


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    Full Text Available The presence of marine alien species in El-Kouf National Park and the neighbouring areas was assessed using a compilation of available information and observations, a field survey conducted on October 2010 in the framework of the MedMPAnet project and results of further monitoring during June and September 2012. A total of 9 alien species were reported: the Rhodophyta Asparagopsis taxiformis (Delile Trevisan de Saint-Léon, the Chlorophyta Caulerpa racemosa var. cylindracea (Sonder Verlaque, Huisman & Boudouresque, the crab Percnon gibbesi (H. Milne-Edwards, 1853 and the fishes Fistularia commersonii Rüppell, 1838, Siganus luridus (Rüppell, 1829, Siganus rivulatus Forsskål, 1775, Pempheris vanicolensis Cuvier, 1831, Lagocephalus sceleratus (Gmelin, 1789 and Sphyraena flavicauda Rüppell, 1838. Several of them were until now unknown for the National Park. The list of alien marine species of Libya is updated and discussed. Until now 63 marine aliens species were recorded along the Libyan coasts. These include 3 Foraminifera, 3 Ochrophyta, 5 Rhodophyta, 5 Chlorophyta, 1 Magnoliophyta, 11 Arthropoda, 13 Mollusca, 1 Echinodermata and 21 Chordata. Among these Non Indigenous Species, 43 are known as established along the Libyan coast including 8 invasive, 11 casual, 6 questionable, 3 cryptogenic and 1 unknown. An in-depth study of the marine organisms would substantially increase the number of alien species occurring in Libya. Monitoring of marine assemblages of MPAs is a valuable opportunity to go further into the knowledge of native and introduced species.

  16. How many marine aliens in Europe?

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    Stelios Katsanevakis


    Full Text Available In the framework of the European Alien Species Information Network (EASIN;, an inventory of marine alienspecies in Europe was created by critically reviewing existing information in 34 global, European, regional and national databases. In total, 1369 marine alien species have been reported in the European seas (including 110 cryptogenic and 139 questionable species; this is a substantial increase from the 737 species previously reported in 2009 based on the DAISIE (Delivering Alien Invasive Species Inventories for Europe; dataset. Most of the reported species were invertebrates (63.3%, followed by chromists (13.7%, vertebrates (11.6%, and plants (10.1%. Mollusca is the most numerous phylum, followed by Arthropoda, Chordata, and Annelida. Thecountries with the highest reported numbers of marine alien species were Israel, Turkey, Italy, France, Egypt and Greece. A reporting bias is evident as efforts for monitoring and reporting alien species vary among countries.

  17. Phylogeny drives large scale patterns in Australian marine bioactivity and provides a new chemical ecology rationale for future biodiscovery. (United States)

    Evans-Illidge, Elizabeth A; Logan, Murray; Doyle, Jason; Fromont, Jane; Battershill, Christopher N; Ericson, Gavin; Wolff, Carsten W; Muirhead, Andrew; Kearns, Phillip; Abdo, David; Kininmonth, Stuart; Llewellyn, Lyndon


    Twenty-five years of Australian marine bioresources collecting and research by the Australian Institute of Marine Science (AIMS) has explored the breadth of latitudinally and longitudinally diverse marine habitats that comprise Australia's ocean territory. The resulting AIMS Bioresources Library and associated relational database integrate biodiversity with bioactivity data, and these resources were mined to retrospectively assess biogeographic, taxonomic and phylogenetic patterns in cytotoxic, antimicrobial, and central nervous system (CNS)-protective bioactivity. While the bioassays used were originally chosen to be indicative of pharmaceutically relevant bioactivity, the results have qualified ecological relevance regarding secondary metabolism. In general, metazoan phyla along the deuterostome phylogenetic pathway (eg to Chordata) and their ancestors (eg Porifera and Cnidaria) had higher percentages of bioactive samples in the assays examined. While taxonomy at the phylum level and higher-order phylogeny groupings helped account for observed trends, taxonomy to genus did not resolve the trends any further. In addition, the results did not identify any biogeographic bioactivity hotspots that correlated with biodiversity hotspots. We conclude with a hypothesis that high-level phylogeny, and therefore the metabolic machinery available to an organism, is a major determinant of bioactivity, while habitat diversity and ecological circumstance are possible drivers in the activation of this machinery and bioactive secondary metabolism. This study supports the strategy of targeting phyla from the deuterostome lineage (including ancestral phyla) from biodiverse marine habitats and ecological niches, in future biodiscovery, at least that which is focused on vertebrate (including human) health.

  18. Natural variation of model mutant phenotypes in Ciona intestinalis.

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    Paolo Sordino

    Full Text Available BACKGROUND: The study of ascidians (Chordata, Tunicata has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. CONCLUSIONS/SIGNIFICANCE: Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity.

  19. Toll-like receptors (TLRs) in aquatic animals: signaling pathways, expressions and immune responses. (United States)

    Rauta, Pradipta R; Samanta, Mrinal; Dash, Hirak R; Nayak, Bismita; Das, Surajit


    The innate system's recognition of non-self and danger signals is mediated by a limited number of germ-line encoded pattern recognition receptors (PRRs) that recognize pathogen associated molecular patterns (PAMPs). Toll-like receptors (TLRs) are single, non-catalytic, membrane-spanning PRRs present in invertebrates and vertebrates. They act by specifically recognizing PAMPs of a variety of microbes and activate signaling cascades to induce innate immunity. A large number of TLRs have been identified in various aquatic animals of phyla Cnidaria, Annelida, Mollusca, Arthropoda, Echinodermata and Chordata. TLRs of aquatic and warm-blooded higher animals exhibit some distinctive features due to their diverse evolutionary lineages. However, majority of them share conserve signaling pathways in pathogen recognition and innate immunity. Functional analysis of novel TLRs in aquatic animals is very important in understanding the comparative immunology between warm-blooded and aquatic animals. In additions to innate immunity, recent reports have highlighted the additional roles of TLRs in adaptive immunity. Therefore, vaccines against many critical diseases of aquatic animals may be made more effective by supplementing TLR activators which will stimulate dendritic cells. This article describes updated information of TLRs in aquatic animals and their structural and functional relationship with warm-blooded animals.

  20. Morphology of the muscles of the shoulder, arms and forearms of the coati (Nasua nasua

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    Amilton Cesar dos Santos


    Full Text Available The coati is an animal that belongs to the Phylum Chordata, the Class Mammalia, the Order Carnivora and the Procyonidae family. The striking feature of the family Procyonidae is the presence of five digits on the paws. These animals are classified as plantigrades and can do hand movements in different directions. It has habits of climbing trees to procreate, fleeing from danger, and sleeping at night. It feeds on fruits, small vertebrates, insects, nectar, eggs and vegetables. For this work were used three euthanized animals, from the Scientific Breeding Center (CECRIMPAS – UNIFEOB authorized by IBAMA (Process nº 02027.003731/04-76, fixed in formaldehyde solution 10%. This work describes the morphology of the muscles of the forelimb of the coati, through dissection and photographic documentation. In the studied species, we found anatomical adaptations of thoracic limb muscles which had a mass volume much greater than in other species (puma, alpaca, dog, cat, lhama and Cebus apella monkeys, and this fact was found to be directly related to their abilities in climbing and handicraft.

  1. Comparative and Evolutionary Analysis of the Interleukin 17 Gene Family in Invertebrates.

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    Xian-De Huang

    Full Text Available Interleukin 17 (IL-17 is an important pro-inflammatory cytokine and plays critical roles in the immune response to pathogens and in the pathogenesis of inflammatory and autoimmune diseases. Despite its important functions, the origin and evolution of IL-17 in animal phyla have not been characterized. As determined in this study, the distribution of the IL-17 family among 10 invertebrate species and 7 vertebrate species suggests that the IL-17 gene may have originated from Nematoda but is absent from Saccoglossus kowalevskii (Hemichordata and Insecta. Moreover, the gene number, protein length and domain number of IL-17 differ widely. A comparison of IL-17-containing domains and conserved motifs indicated somewhat low amino acid sequence similarity but high conservation at the motif level, although some motifs were lost in certain species. The third disulfide bond for the cystine knot fold is formed by two cysteine residues in invertebrates, but these have been replaced by two serine residues in Chordata and vertebrates. One third of invertebrate IL-17 proteins were found to have no predicted signal peptide. Furthermore, an analysis of phylogenetic trees and exon-intron structures indicated that the IL-17 family lacks conservation and displays high divergence. These results suggest that invertebrate IL-17 proteins have undergone complex differentiation and that their members may have developed novel functions during evolution.

  2. Molecular characterization and expression analysis of the first Porifera tumor necrosis factor superfamily member and of its putative receptor in the marine sponge Chondrosia reniformis. (United States)

    Pozzolini, Marina; Scarfì, Sonia; Ghignone, Stefano; Mussino, Francesca; Vezzulli, Luigi; Cerrano, Carlo; Giovine, Marco


    Here we report the molecular cloning and characterization of the first Tumor Necrosis Factor homologous and of its putative receptor in the marine sponge Chondrosia reniformis: chTNF and chTNFR, respectively. The deduced chTNF amino acid sequence is a type II transmembrane protein containing the typical TNFSF domain. Phylogenetic analysis reveals that chTNF is more related to Chordata TNFs rather than to other invertebrates. chTNF and chTNFR are constitutively expressed both in the ectosome and in the choanosome of the sponge, with higher levels in the ectosome. chTNF and chTNFR mRNAs were monitored in sponge fragmorphs treated with Gram(+) or Gram(-) bacteria. chTNF was significantly upregulated in Gram(+)-treated fragmorphs as compared to controls, while chTNFR was upregulated by both treatments. Finally, the possible chTNF fibrogenic role in sponge fragmorphs was studied by TNF inhibitor treatment measuring fibrillar and non fibrillar collagen gene expression; results indicate that the cytokine is involved in sponge collagen deposition and homeostasis.

  3. Alfacalcidol in men with osteoporosis: a prospective, observational, 2-year trial on 214 patients. (United States)

    Ringe, J D; Farahmand, P; Schacht, E


    Due to pleiotropic-synergistic actions on bone, muscle, gut, brain and different other non-skeletal tissues, alfacalcidol is an interesting drug for treating osteoporosis. In studies on glucocorticoid-induced osteoporosis, men have always been treated with calcitriol or this active D-hormone prodrug, but there is no study of male patients only in the literature. The AIM-Trial (Alfacalcidol In Men) is an extension of the control group (n = 158) of our former risedronate study in male osteoporosis (Ringe et al. in Rheumatol Int 29:311-315, 2009). In that study, we treated daily those controls with prevalent vertebral fractures with 1 μg alfacalcidol + 500 mg calcium (group A) and those without prevalent vertebral fractures with 1,000 IU plain vitamin D (Vit. D) + 1,000 mg calcium (group B). Subsequently, we added an additional 56 pairs of patients to these two groups: 28 with and 28 without prevalent vertebral fractures, reaching a total of 214 cases. That means with this design, we are comparing two groups with a different risk at onset. Due to the prevalent vertebral fractures and lower average bone mineral density (BMD) values, there was a higher risk of incident fractures in group A. After 2 years, we found significantly higher increases in lumbar spine BMD (+3.2 vs. +0.8 %) and total hip BMD (+1.9 vs. -0.9 %) in group A and B, respectively. Eighteen incident falls were recorded in the alfacalcidol group and 38 in the group treated with Vit. D (p = 0.041). There were significantly lower rates of patients with new vertebral and non-vertebral fractures in group A than in group B. Back pain was significantly reduced only with alfacalcidol. Concerning the incidence of new non-vertebral fractures, we found that there was a relation to renal function in the two groups. The advantage for alfacalcidol was mainly due to a higher non-vertebral fracture-reducing potency in patients with a creatinine clearance (CrCl) below 60 ml/min (p = 0.0019). There

  4. Global characterization of interferon regulatory factor (IRF genes in vertebrates: Glimpse of the diversification in evolution

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    Xu Zhen


    Full Text Available Abstract Background Interferon regulatory factors (IRFs, which can be identified based on a unique helix-turn-helix DNA-binding domain (DBD are a large family of transcription factors involved in host immune response, haemotopoietic differentiation and immunomodulation. Despite the identification of ten IRF family members in mammals, and some recent effort to identify these members in fish, relatively little is known in the composition of these members in other classes of vertebrates, and the evolution and probably the origin of the IRF family have not been investigated in vertebrates. Results Genome data mining has been performed to identify any possible IRF family members in human, mouse, dog, chicken, anole lizard, frog, and some teleost fish, mainly zebrafish and stickleback, and also in non-vertebrate deuterostomes including the hemichordate, cephalochordate, urochordate and echinoderm. In vertebrates, all ten IRF family members, i.e. IRF-1 to IRF-10 were identified, with two genes of IRF-4 and IRF-6 identified in fish and frog, respectively, except that in zebrafish exist three IRF-4 genes. Surprisingly, an additional member in the IRF family, IRF-11 was found in teleost fish. A range of two to ten IRF-like genes were detected in the non-vertebrate deuterostomes, and they had little similarity to those IRF family members in vertebrates as revealed in genomic structure and in phylogenetic analysis. However, the ten IRF family members, IRF-1 to IRF-10 showed certain degrees of conservation in terms of genomic structure and gene synteny. In particular, IRF-1, IRF-2, IRF-6, IRF-8 are quite conserved in their genomic structure in all vertebrates, and to a less degree, some IRF family members, such as IRF-5 and IRF-9 are comparable in the structure. Synteny analysis revealed that the gene loci for the ten IRF family members in vertebrates were also quite conservative, but in zebrafish conserved genes were distributed in a much longer distance in

  5. Superiority of alfacalcidol over plain vitamin D in the treatment of glucocorticoid-induced osteoporosis. (United States)

    Ringe, J D; Dorst, A; Faber, H; Schacht, E; Rahlfs, V W


    Supplementation therapy with plain vitamin D plus calcium is in general regarded as effective prevention or first-step treatment of glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to compare the therapeutic efficacy of the D-hormone analog alfacalcidol with plain vitamin D in patients with established GIOP with or without vertebral fractures. Patients on long-term glucocorticoid (GC) therapy were included as matched pairs to receive randomly either 1 microg alfacalcidol plus 500 mg calcium per day (group A, n=103) or 1000 IU vitamin D3 plus 500 mg calcium (group B, n=101). The two groups were well matched in terms of mean age, sex ratio, mean height and weight, daily dosage, and duration of GC therapy, and the percentages of the three underlying diseases included chronic obstructive pulmonary disease, rheumatoid arthritis, and polymyalgia rheumatica. The baseline mean bone mineral density (BMD) values at the lumbar spine for the two groups were -3.26 (alfacalcidol) and -3.25 (vitamin D(3)) and, at the femoral neck, -2.81 and -2.84, respectively (T scores). Rates of prevalent vertebral and nonvertebral fractures did not differ between groups. During the 3-year study, we observed a median percentage increase of BMD at the lumbar spine of 2.4% in group A and a loss of 0.8% in group B ( Pvitamin D group (risk reduction 0.61, 95% CI 0.24-0.81, P=0.005). The 3-year rates of patients with at least one new nonvertebral fracture were 15% in the alfacalcidol group and 25% in the vitamin D group (risk reduction 0.41, 95% CI 0.06-0.68, P=0.081). The 3-year rates of patients with at least one new fracture of any kind were 19.4% among those treated with alfacalcidol and 40.65% with vitamin D (risk reduction 0.52, 95% CI 0.25-0.71, P=0.001). In accordance with the observed fracture rates, the alfacalcidol group showed a substantially larger decrease in back pain than the plain vitamin D group ( Pvitamin D group had moderate hypercalcemia. We conclude that

  6. Sustained efficacy of risedronate in men with primary and secondary osteoporosis: results of a 2-year study. (United States)

    Ringe, Johann D; Farahmand, Parvis; Faber, Herbert; Dorst, Alfred


    The aim of this study was to assess the effect of treatment with risedronate 5 mg daily relative to control in men with primary or secondary osteoporosis over 2 years. Osteoporosis is a common condition in men that can have serious clinical consequences. In an earlier interim report, we found that 1 year of risedronate therapy resulted in significant increases in bone mineral density (BMD) and a significant reduction in vertebral fractures compared to control in men with osteoporosis. We conducted an open-label, prospective, match-control trial on men with primary or secondary osteoporosis in a single center, outpatient setting. Men with primary or secondary osteoporosis, as defined by a baseline lumbar spine BMD T-score vitamin D (800 IU) or to a control group (daily alfacalcidol (1 microg) plus calcium (500 mg) for those with prevalent vertebral fractures; daily vitamin D (800 IU) plus calcium (1,200 mg) for those without previous vertebral fractures). Primary study end points were identified prior to study initiation as the incidence of new vertebral fractures and changes in BMD at the lumbar spine, femoral neck, and total hip. Other end points included incidence of nonvertebral fractures and change in body height and back pain. Compared to control, the incidence of new vertebral fractures was significantly reduced in the risedronate 5 mg daily group at 2 years [14/152 (9.2%) for risedronate vs. 35/148 (23.6%) for control (61% risk reduction; P = 0.0026)]. Treatment with risedronate 5 mg daily also resulted in significant improvements in BMD at 2 years at all three skeletal sites (lumbar spine, 6.5 vs. 2.2%; femoral neck, 3.2 vs. 0.6%; total hip, 4.4 vs. 0.4% (P back pain were also observed in risedronate-treated patients relative to control. In this 2-year study, daily 5 mg risedronate significantly reduced the risk of vertebral and nonvertebral fractures, improved BMD, decreased height loss, and reduced back pain in men with osteoporosis. Efficacy was

  7. Alfacalcidol versus plain vitamin D in the treatment of glucocorticoid/inflammation-induced osteoporosis. (United States)

    Ringe, Johann D; Faber, Herbert; Fahramand, Parvis; Schacht, Erich


    Treatment with plain vitamin D is a nutritional substitute, while the application of alfacalcidol is an active hormonal therapy. Due to strong feedback regulation, plain vitamin D is not activated in the kidney in vitamin-replete patients, while alfacalcidol, having been hydroxylated at position 1, bypasses regulation and increases available amounts of active D-hormone in different target tissues. Nevertheless, a majority of physicians still prescribe plain vitamin D plus calcium as a first-step prevention or even as therapy for glucocorticoid (GC) induced osteoporosis. This article summarizes results of our previous study comparing the therapeutic efficacy of the D-hormone analog alfacalcidol to plain vitamin D in patients with established GC induced osteoporosis with or without vertebral fracture. Patients taking longterm GC therapy were included as well-matched pairs to receive randomly either 1 microg alfacalcidol plus 500 mg calcium per day (group A, n = 103) or 1000 IU vitamin D3 plus 500 mg calcium (group B, n = 101). The mean bone mineral density (BMD) values at baseline for the 2 groups for alfacalcidol and vitamin D3, respectively, were: lumbar spine T score -3.26 and -3.25; femoral neck -2.81 and -2.84. Rates of prevalent vertebral and nonvertebral fractures were not different between groups. In the 3 year study we observed in the alfacalcidol group as compared with the plain vitamin D group, respectively: a 3 year median percentage increase of BMD at the lumbar spine of 2.4% versus -0.8% (p vitamin D group, respectively: a 3 year rate of patients with > or = 1 new vertebral fracture of 9.7% versus 24.8% (risk reduction: 0.61; 95% CI 0.24 to 0.81; p = 0.005); a 3 year rate of patients with > or = 1 new nonvertebral fracture of 15% versus 25% (risk reduction: 0.41; 95% CI -0.06 to 0.68; p = 0.081); a 3 year rate of patients with > or = 1 new fracture of any kind of 19.4% versus 40.6% (risk reduction: 0.52; 95% CI 0.25 to 0.71; p = 0.001). In accordance

  8. Cost-Effectiveness of Zoledronic Acid to Prevent and Treat Postmenopausal Osteoporosis in Comparison with Routine Medical Treatment (United States)

    Golmohamdi, Fateme Rostami; Abbasi, Mahnaz; Karyani, Ali Kazemi; Sari, Ali Akbari


    Introduction Fractures caused by osteoporosis are prevalent among elderly females, which reduce quality of life significantly. This study aimed at comparing cost-effectiveness of Zoledronic acid in preventing and treating post-menopause osteoporosis as compared with routine medical treatment. Methods This cost-effectiveness study was carried out retrospectively from the Ministry of Health and insurance organizations perspective. Costs were evaluated based on the cost estimation of a sample of patients. Outcomes were obtained from a systematic review. The Cost-Effectiveness Ratio (CER) and incremental cost-effectiveness ratio (ICER) for outcome of femoral neck Bone Mineral Density (BMD), hip trochanter BMD, total hip BMD and lumbar spine BMD and cost-benefit of consuming Zoledronic Acid were calculated for fracture outcome obtained from reviewing hospital records. Results The results and the ICER calculated for study outcomes indicated that one percent increase of BMD on femoral neck BMD requires further cost of $386. One percent increase of BMD on hip trochanter BMD requires further cost of $264. One percent increase of BMD on total hip BMD requires further cost of $388, one percent increase of BMD on lumbar spine BMD requires further cost of $347. The Cost Benefit Analysis (CBA) calculated for vertebral and hip fracture, non-vertebral fracture, any clinical fracture, and morphometric fracture for a 36-month period were about 0.82, 0.57, and 1.06, respectively. Vertebral and hip fractures, and non-vertebral fractures or any clinical fracture for a 12-month period were calculated as 1.14 and 0.64, respectively. In other words, Zoledronic acid consumption approach is a cheaper and better approach based on an economic assessment, and it can be considered as a dominant approach. Conclusion According to the cost-effectiveness of zoledronic acid in the prevention and treatment of osteoporosis in women, despite the costs, it is recommended that insurance coverage for the

  9. TRPV4 deficiency causes sexual dimorphism in bone metabolism and osteoporotic fracture risk. (United States)

    van der Eerden, B C J; Oei, L; Roschger, P; Fratzl-Zelman, N; Hoenderop, J G J; van Schoor, N M; Pettersson-Kymmer, U; Schreuders-Koedam, M; Uitterlinden, A G; Hofman, A; Suzuki, M; Klaushofer, K; Ohlsson, C; Lips, P J A; Rivadeneira, F; Bindels, R J M; van Leeuwen, J P T M


    We explored the role of transient receptor potential vanilloid 4 (TRPV4) in murine bone metabolism and association of TRPV4 gene variants with fractures in humans. Urinary and histomorphometrical analyses demonstrated reduced osteoclast activity and numbers in male Trpv4(-/-) mice, which was confirmed in bone marrow-derived osteoclast cultures. Osteoblasts and bone formation as shown by serum procollagen type 1 amino-terminal propeptide and histomorphometry, including osteoid surface, osteoblast and osteocyte numbers were not affected in vivo. Nevertheless, osteoblast differentiation was enhanced in Trpv4(-/-) bone marrow cultures. Cortical and trabecular bone mass was 20% increased in male Trpv4(-/-) mice, compared to sex-matched wild type (Trpv4(+/+)) mice. However, at the same time intracortical porosity was increased and bone matrix mineralization was reduced. Together, these lead to a maximum load, stiffness and work to failure of the femoral bone, which were not different compared to Trpv4(+/+) mice, while the bone material was less resistant to stress and less elastic. The differential impacts on these determinants of bone strength were likely responsible for the lack of any changes in whole bone strength in the Trpv4(-/-) mice. None of these skeletal parameters were affected in female Trpv4(-/-) mice. The T-allele of rs1861809 SNP in the TRPV4 locus was associated with a 30% increased risk (95% CI: 1.1-1.6; p=0.013) for non-vertebral fracture risk in men, but not in women, in the Rotterdam Study. Meta-analyses with the population-based LASA study confirmed the association with non-vertebral fractures in men. This was lost when the non-population-based studies Mr. OS and UFO were included. In conclusion, TRPV4 is a male-specific regulator of bone metabolism, a determinant of bone strength, and a potential risk predictor for fractures through regulation of bone matrix mineralization and intra-cortical porosity. This identifies TRPV4 as a unique sexually

  10. Low-Level Cadmium Exposure Is Associated With Decreased Bone Mineral Density and Increased Risk of Incident Fractures in Elderly Men: The MrOS Sweden Study. (United States)

    Wallin, Maria; Barregard, Lars; Sallsten, Gerd; Lundh, Thomas; Karlsson, Magnus K; Lorentzon, Mattias; Ohlsson, Claes; Mellström, Dan


    One risk factor for osteoporosis that has attracted increasing attention in recent years is exposure to cadmium. The aim of this study was to examine the associations between low-level cadmium exposure, from diet and smoking, and bone mineral density (BMD) and incident fractures in elderly men. The study population consisted of 936 men from the Swedish cohort of the Osteoporotic Fractures in Men (MrOS) study, aged 70 to 81 years at inclusion (years 2002 to 2004), with reliable data on cadmium in urine (U-Cd) analyzed using inductively coupled plasma mass spectrometry in baseline samples. The participants also answered a questionnaire on lifestyle factors and medical history. BMD was measured at baseline using dual-energy X-ray absorptiometry (DXA) in the total body, hip, and lumbar spine. During the follow-up period (until 2013), all new fractures were registered by date and type. Associations between BMD and U-Cd were assessed using multiple linear regression, and associations between incident fractures and baseline U-Cd were analyzed using Cox regression. In both cases, a number of potential confounders and other risk factors (eg, age, smoking, body mass index [BMI], and physical activity) were included in the models. We found significant negative associations between U-Cd and BMD, with lower BMD (4% to 8%) for all sites in the fourth quartile of U-Cd, using the first quartile as the reference. In addition, we found positive associations between U-Cd and incident fractures, especially nonvertebral osteoporosis fractures in the fourth quartile of U-Cd, with hazard ratios of 1.8 to 3.3 in the various models. U-Cd as a continuous variable was significantly associated with nonvertebral osteoporosis fractures (adjusted hazard ratio 1.3 to 1.4 per μg Cd/g creatinine), also in never-smokers, but not with the other fracture groups (all fractures, hip fractures, vertebral fractures, and other fractures). Our results indicate that even relatively low cadmium exposure

  11. Effect of dietary B vitamins on BMD and risk of fracture in elderly men and women: the Rotterdam study. (United States)

    Yazdanpanah, Nahid; Zillikens, M Carola; Rivadeneira, Fernando; de Jong, Robert; Lindemans, Jan; Uitterlinden, André G; Pols, Huibert A P; van Meurs, Joyce B J


    A mildly elevated homocysteine (Hcy) level is a novel and potentially modifiable risk factor for age-related osteoporotic fractures. Elevated Hcy levels can have a nutritional cause, such as inadequate intake of folate, riboflavin, pyridoxine or cobalamin, which serve as cofactors or substrates for the enzymes involved in the Hcy metabolism. We examined the association between intake of Hcy-related B vitamin (riboflavin, pyridoxine, folate and cobalamin) and femoral neck bone mineral density BMD (FN-BMD) and the risk of fracture in a large population-based cohort of elderly Caucasians. We studied 5304 individuals aged 55 years and over from the Rotterdam Study. Dietary intake of nutrients was obtained from food frequency questionnaires. Incident non-vertebral fractures were recorded during a mean follow-up period of 7.4 years, and vertebral fractures were assessed by X-rays during a mean follow-up period of 6.4 years. We observed a small but significant positive association between dietary pyridoxine (beta = 0.09, p = 1 x 10(-8)) and riboflavin intake (beta = 0.06, p = 0.002) and baseline FN-BMD. In addition, after controlling for gender, age and BMI, pyridoxine intake was inversely correlated to fracture risk. As compared to the three lowest quartiles, individuals in the highest quartile of age- and energy-adjusted dietary pyridoxine intake had a decreased risk of non-vertebral fractures (HR = 0.77, 95% CI = 0.65-0.92, p = 0.005) and of fragility fractures (HR = 0.55, 95% CI = 0.40-0.77, p = 0.0004). Further adjustments for other dietary B vitamins (riboflavin, folate and cobalamin), dietary intake of calcium, vitamin D, vitamin A and vitamin K, protein and energy intake, smoking and BMD did not essentially modify these results. We conclude that increased dietary riboflavin and pyridoxine intake was associated with higher FN-BMD. Furthermore, we found a reduction in risk of fracture in relation to dietary pyridoxine intake independent of BMD. These findings

  12. [Not Available]. (United States)

    Nakov, L

    The teaching of Biology at the Medical Faculty in Sofia started in 1918 with Botany and Zoology. Already in the next year, it was radically changed by Metodii Popov: 1. Instead of Botany he introduced General Biology, and instead of Zoology - Parasitology (including a general review of the evolution of non-vertebrate animals) and Comparative Anatomy of the Vertebrates; 2. He adapted the teaching of Biology to the needs of the medical education. Those changes were possible thanks to the considerable medical background of M. Popov - it started in 1911 with suitable specialization and research activities, and continued with the establishment of Department of Biology and the Medical Faculty, and the involvement of medics, besides biologists, in its academic staff. During the past years there have been a lot of changes in the curriculum both in its schedule and contents. Some of them were as a result of the development of the biological science and the integration with the other disciples, but some were forced by the administration. Today the students have 90 hours of lectures and a practical course of 90 hours as well. They have at their disposal textbooks on "Biology", "Parasitology" and "Comparative Anatomy of the Vertebrates", as well as, a "Textbook for the practical Course on Biology". Their knowledge is evaluated during the practical course, at two colloquia, and at a practical and theoretical (oral) exam at the end of the first year of education.

  13. Denosumab for Elderly Men with Osteoporosis: A Cost-Effectiveness Analysis from the US Payer Perspective

    Directory of Open Access Journals (Sweden)

    Stuart Silverman


    Full Text Available Purpose. To evaluate the cost-effectiveness of denosumab versus other osteoporotic treatments in older men with osteoporosis from a US payer perspective. Methods. A lifetime cohort Markov model previously developed for postmenopausal osteoporosis (PMO was used. Men in the model were 78 years old, with a BMD T-score of −2.12 and a vertebral fracture prevalence of 23%. During each 6-month Markov cycle, patients could have experienced a hip, vertebral or nonhip, nonvertebral (NHNV osteoporotic fracture, remained in a nonfracture state, remained in a postfracture state, or died. Background fracture risks, mortality rates, persistence rates, health utilities, and medical and drug costs were derived from published sources. Previous PMO studies were used for drug efficacy in reducing fracture risk. Lifetime expected costs and quality-adjusted life-years (QALYs were estimated for denosumab, generic alendronate, risedronate, ibandronate, teriparatide, and zoledronate. Results. Denosumab had an incremental cost-effectiveness ratio (ICER of $16,888 compared to generic alendronate and dominated all other treatments. Results were most sensitive to changes in costs of denosumab and the relative risk of hip fracture. Conclusion. Despite a higher annual treatment cost compared to other medications, denosumab is cost-effective compared to other osteoporotic treatments in older osteoporotic US men.

  14. Proceedings of the Eighth Annual Santa Fe Bone Symposium, August 3-4, 2007. (United States)

    Lewiecki, E Michael; Bilezikian, John P; Cooper, Cyrus; Hochberg, Marc C; Luckey, Marjorie M; Maricic, Michael; Miller, Paul D


    The Eighth Annual Santa Fe Bone Symposium convened August 3-4, 2007, in Santa Fe, New Mexico, USA, immediately preceded by the Research Symposium in Metabolic Bone Disease and Osteoporosis Update for Endocrine Fellows, and followed by the International Society for Clinical Densitometry (ISCD) Bone Densitometry Course. The symposium faculty consists of internationally recognized experts in osteoporosis and metabolic bone disease who presented state-of-the-art research data and late-breaking developments in the fields of osteoporosis, metabolic bone disease, and assessment of skeletal health. The presentations and numerous interactive discussions that followed focused on applying what is known from clinical trials, knowledge of bone pathophysiology, and the mechanisms of action of therapeutic interventions, to making real-world patient management decisions. Topics included an update on reimbursement issues for bone density testing in the United States, a report on the 2007 ISCD Pediatric and Adult Position Development Conferences, present and future therapeutic concepts, new paradigms for fracture risk assessment and intervention thresholds, evaluation for secondary causes of osteoporosis, nonvertebral fracture risk reduction-medical evidence and clinical practice, epidemiological insights into the prevention of osteoporotic fractures, osteonecrosis of the jaw facts and fictions, and osteomalacia. Presented here are short essays based on the key clinical presentations of the 2007 Santa Fe Bone Symposium.

  15. [Therapy of glucocorticoid-induced osteoporosis with alfacalcidol/calcium and vitamin D/calcium]. (United States)

    Ringe, J D; Cöster, A; Meng, T; Schacht, E; Umbach, R


    Calcium/vitamin D supplementation is generally used as a first step treatment of glucocorticoid-induced osteoporosis (GIOP). The aim of this trial was to compare the efficacy of the D-hormone alfacalcidol with plain vitamin D in patients with established GIOP with or without vertebral fractures. Patients on long-term glucocorticoid-therapy were treated either with 1 microgram alfacalcidol plus 5000 mg calcium (group A: n = 43) or with 1000 IU vitamin D plus 500 mg calcium (group B: n = 42). The two groups were not different in respect to initial characteristics such as age, sex distribution, concomittant diseases, bone mineral density (mean T-score values at lumbar spine and femoral neck: -3.29 and -3.25 resp.), and in the number of prevalent vertebral and non-vertebral fractures. During the 3 years of treatment we found a significant increase in lumbar spine density in group A (+2.0%, p back pain only in group A (p vitamin D in GIOP.

  16. Treatment of glucocorticoid-induced osteoporosis with alfacalcidol/calcium versus vitamin D/calcium. (United States)

    Ringe, J D; Cöster, A; Meng, T; Schacht, E; Umbach, R


    Vitamin D/calcium substitution is generally regarded as an effective first step treatment for glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to evaluate the efficacy of the active vitamin D metabolite alfacalcidol (1alpha) compared with the native vitamin D(3) in patients with established GIOP with or without vertebral fractures. Patients on long-term corticoid therapy were given either 1 microg alfacalcidol plus 500 mg calcium per day (group A, n = 43) or 1000 IU vitamin D(3) plus 500 mg calcium (group B, n = 42). The two groups were alike in age range, sex ratio, percentages of underlying diseases, average initial bone density values (lumbar spine: mean T-score -3.28 and -3.25, respectively), and rates of vertebral and nonvertebral fractures. During the 3-year study we found a small but significant increase of lumbar spine density in group 1alpha (+2.0%, P back pain (P vitamin D group. We conclude that with the doses used in this trial, alfacalcidol is superior to vitamin D in the treatment of established GIOP.

  17. Refinement of the ECETOC approach to identify endocrine disrupting properties of chemicals in ecotoxicology. (United States)

    Weltje, Lennart; Wheeler, James R; Weyers, Arnd; Galay-Burgos, Malyka


    To use and implement an assessment scheme for the evaluation of endocrine disrupting properties of chemicals in ecotoxicology, the types of effect need to be agreed. Effects that merit further consideration in this context should fulfil the following three criteria: caused by an endocrine mode of action, be adverse, and be relevant at the population level to reflect the protection goal of ecotoxicological assessments. Thereafter, a comparison of effect values, regardless of the causative mechanisms, should be made, firstly to determine if endocrine toxicity generates the lowest endpoint within a taxon, and secondly if it is the lowest endpoint compared to that of other taxa living in the same compartment. These comparisons inform on two levels of specificity and determine if endocrine-mediated side-effects determine the ecotoxicological profile of a chemical. Various quantitative measures for the assessment of potency are also presented, which could assist in determining how to handle substances in the risk assessment when a regulatory concern is identified. Finally, derogation criteria should be defined for compounds that were designed as endocrine disruptors for non-vertebrates and those for which there is 'negligible exposure'. This paper discusses and provides proposals on how to apply these concepts for assessment of substances.

  18. Effects of strontium malonate (NB S101) on the compositional, structural and biomechanical properties of calcified tissues in rats and dogs

    DEFF Research Database (Denmark)

    Raffalt, Anders Christer

    Strontium is known to have a positive effect on bone by concomitantly increasing bone formation and decreasing bone resorption, thereby providing a sustained skeletal benefit. Strontium ranelate (SrR) has been shown to reduce the risk of both vertebral and non-vertebral fractures in patients...... tissues. The highest concentrations were found in rat incisor, which contained an average of 45 ± 11 mg g-1 Sr in the highest dose group, corresponding to a 450-fold increase compared with placebo. The Sr/(Sr+Ca)mol% in the four groups were respectively 0.015, 1.2, 5.8 and 7.7 for incisors and 0.015, 0.......6, 1.9 and 5.0 for femurs. Sr concentrations in rat incisor and rat femur were strongly correlated with approx. 30% less Sr found in the femurs. A strong correlation between serum Sr and incisor Sr was also observed. In dogs, the highest concentrations of Sr were found in skullcap after 52 weeks...

  19. Hormone replacement therapy and the prevention of postmenopausal osteoporosis. (United States)

    Gambacciani, Marco; Levancini, Marco


    Fracture prevention is one of the public health priorities worldwide. Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis, the most common metabolic bone disease. Different effective treatments for osteoporosis are available. Hormone replacement therapy (HRT) at different doses rapidly normalizes turnover, preserves bone mineral density (BMD) at all skeletal sites, leading to a significant, reduction in vertebral and non-vertebral fractures. Tibolone, a selective tissue estrogenic activity regulator (STEAR), is effective in the treatment of vasomotor symptoms, vaginal atrophy and prevention/treatment of osteoporosis with a clinical efficacy similar to that of conventional HRT. Selective estrogen receptor modulators (SERMs) such as raloxifene and bazedoxifene reduce turnover and maintain or increase vertebral and femoral BMD and reduce the risk of osteoporotic fractures. The combination of bazedoxifene and conjugated estrogens, defined as tissue selective estrogen complex (TSEC), is able to reduce climacteric symptoms, reduce bone turnover and preserve BMD. In conclusion, osteoporosis prevention can actually be considered as a major additional benefit in climacteric women who use HRT for treatment of climacteric symptoms. The use of a standard dose of HRT for osteoporosis prevention is based on biology, epidemiology, animal and preclinical data, observational studies and randomized, clinical trials. The antifracture effect of a lower dose HRT or TSEC is supported by the data on BMD and turnover, with compelling scientific evidence.

  20. Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis. (United States)

    Kung, Annie W C; Chu, Eva Y W; Xu, Ling


    Bazedoxifene acetate (WAY-140424; TSE-424) is an oral, nonsteroidal, indole-based selective estrogen receptor modulator (SERM) being developed for the prevention and treatment of osteoporosis. Preclinical studies on bazedoxifene have demonstrated estrogen agonist effects on the skeleton and lipid metabolism but not on breast and uterine endometrium. In combination with estrogen, bazedoxifene antagonizes the stimulatory action of estrogens on proliferation of breast cancer cells and endometrium. Phase III clinical studies have shown favorable effects on the skeleton without stimulation of endometrium and breast. Bazedoxifene prevents bone loss in postmenopausal women without osteoporosis and reduces vertebral fractures in women with postmenopausal osteoporosis. In women at high risk of fracture with multiple risk factors, bazedoxifene reduces nonvertebral fracture risk in post-hoc analysis. Bazedoxifene in combination with conjugated estrogens represents a new form of therapeutic agents for the treatment of postmenopausal symptoms and prevention of postmenopausal osteoporosis. Clinical trials with bazedoxifene/conjugated estrogens have shown beneficial effects on bone mineral density and bone turnover markers with improvement in vasomotor symptoms and little or no stimulation of breast and endometrium.

  1. Lasofoxifene for the prevention and treatment of postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    E Michael Lewiecki


    Full Text Available E Michael LewieckiNew Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USAAbstract: Lasofoxifene is a selective estrogen receptor modulator (estrogen agonist/antagonist that has completed phase III trials to evaluate safety and efficacy for the prevention and treatment of osteoporosis and for the treatment of vaginal atrophy in postmenopausal women. In postmenopausal women with low or normal bone mineral density (BMD, lasofoxifene increased BMD at the lumbar spine and hip and reduced bone turnover markers compared with placebo. In women with postmenopausal osteoporosis, lasofoxifene increased BMD, reduced bone turnover markers, reduced the risk of vertebral and nonvertebral fractures, and decreased the risk of estrogen receptor-positive breast cancer. In postmenopausal women with low bone mass, lasofoxifene improved the signs and symptoms of vulvovaginal atrophy. Clinical trials show that lasofoxifene is generally well tolerated with mild to moderate adverse events that commonly resolve even with drug continuation. Lasofoxifene has been associated with an increase in the incidence of venous thromboembolic events, hot flushes, muscle spasm, and vaginal bleeding. It is approved for the treatment of postmenopausal women at increased risk for fracture in some countries and is in the regulatory review process in others.Keywords: osteoporosis, SERM, fracture, efficacy, safety, BMD, CP-336,156

  2. Bazedoxifene acetate: a novel selective estrogen receptor modulator for the prevention and treatment of postmenopausal osteoporosis. (United States)

    Chines, Arkadi A; Komm, Barry S


    Postmenopausal osteoporosis is an increasing worldwide health concern affecting an estimated 200 million individuals. Despite a wide range of available treatment options, many patients are not being treated or discontinue therapy. The ongoing need for new osteoporosis therapies has led to the development of new selective estrogen receptor modulators (SERMs) with an ideal tissue selectivity profile and beneficial effects on bone without undesirable effects on the endometrium and breast. Bazedoxifene acetate, a novel SERM in clinical development for the prevention and treatment of postmenopausal osteoporosis, resembles this ideal profile more closely than other currently available SERMs. Results from large prospective phase III trials showed that it increases bone mineral density, reduces bone turnover rate and decreases the risk for new vertebral fractures. Moreover, based on a post hoc analysis of a subgroup of women with a higher risk for fracture, bazedoxifene was demonstrated to significantly reduce the incidence of nonvertebral fractures compared with both raloxifene hydrochloride and placebo. Furthermore, it was reported to be well tolerated, with a favorable safety profile and no evidence of endometrial or breast tissue stimulation. Bazedoxifene represents an important new treatment option for women at risk for osteoporosis and fracture.

  3. Vitamin d and rehabilitation: improving functional outcomes. (United States)

    Shinchuk, Leonid M; Shinchuk, Leonid; Holick, Michael F


    Vitamin D inadequacy is pandemic among rehabilitation patients in both inpatient and outpatient settings. Male and female patients of all ages and ethnic backgrounds are affected. Vitamin D deficiency causes osteopenia, precipitates and exacerbates osteoporosis, causes the painful bone disease osteomalacia, and worsens proximal muscle strength and postural sway. Vitamin D inadequacy can be prevented by sensible sun exposure and adequate dietary intake with supplementation. Vitamin D status is determined by measurement of serum 25-hydroxyvitamin D. The recommended healthful serum level is between 30 and 60 ng/mL. 25-Hydroxyvitamin D levels of >30 ng/mL are sufficient to suppress parathyroid hormone production and to maximize the efficiency of dietary calcium absorption from the small intestine. This can be accomplished by ingesting 1000 IU of vitamin D(3) per day, or by taking 50,000 IU of vitamin D(2) every 2 weeks. Vitamin D toxicity is observed when 25-hydroxyvitamin D levels exceed 150 ng/mL. Identification and treatment of vitamin D deficiency reduces the risk of vertebral and nonvertebral fractures by improving bone health and musculoskeletal function. Vitamin D deficiency and osteomalacia should be considered in the differential diagnosis of patients with musculoskeletal pain, fibromyalgia, chronic fatigue syndrome, or myositis. There is a need for better education of health professionals and the general public regarding the optimization of vitamin D status in the care of rehabilitation patients.

  4. Primary mapping and stratigraphic data and field methods for the Snowmastodon Project (United States)

    Lucking, Carol; Johnson, Kirk R.; Pigati, Jeffery S.; Miller, Ian


    During the Snowmastodon Project, many different people collected data for a wide array of purposes under a variety of conditions. Early in the process and in an attempt to provide project-wide consistency, Kirk Johnson appointed Carol Lucking as the project’s data manager both in the field and the lab. She was responsible for using GIS to create maps on an ongoing basis throughout the project. Jeff Pigati agreed to measure stratigraphic sections and coordinate the collection of various nonvertebrate samples to make sure that all resulting data could be plotted on common diagrams. Kirk Johnson was onsite for the entire project and measured the basin margin stratigraphy on a daily basis as it was destroyed by the digging teams. In the fall of 2010, we treated the upper part of the site (which included discrete excavations for the mammoth, deer, and bison skeletons) as an archaeological excavation and the lower part of the site (which contained isolated mastodon, ground sloth, and bison bones) as a construction salvage site.

  5. [Drug therapy for prevention of falls and fractures]. (United States)

    Ringe, Johann D


    The primary goal in the practical management of osteoporosis is to prevent first or subsequent fractures and thereby to avoid acute or chronic pain and progressive skeletal deformity. Therapeutic strategies should always take the complex pathogenetic mechanisms of fractures into account, especially the fact that mechanical impacts and falls play an important role in the majority of fracture events. Accordingly, recommendations to patients and the selection of drugs should aim at both, falls and fractures. In this context there is an increasing interest in the dual effects of vitamin D on bone and muscle. Controlled studies proved that adequate vitamin D supplementation is able to improve muscle strength, coordination and body sway and thereby reduce the risk of falls and fractures. Alendronate has been studied extensively by large trials of high quality and its efficacy to reduce the risk of vertebral and nonvertebral fractures is in line with the criteria of evidence-based medicine. The innovative combination of 70 mg alendronate with 2,800 IU vitamin D in a once-weekly tablet guarantees a basic supply with this important prohormone for bone and muscle. Due to a regular combined intake an improved compliance can be anticipated which will be followed by better therapeutic results in osteoporosis patients with increased fracture risk.

  6. Increased strontium uptake in trabecular bone of ovariectomized calcium-deficient rats treated with strontium ranelate or strontium chloride. (United States)

    Pemmer, Bernhard; Hofstaetter, Jochen G; Meirer, Florian; Smolek, Stephan; Wobrauschek, Peter; Simon, Rolf; Fuchs, Robyn K; Allen, Matthew R; Condon, Keith W; Reinwald, Susan; Phipps, Roger J; Burr, David B; Paschalis, Eleftherios P; Klaushofer, Klaus; Streli, Christina; Roschger, Paul


    Based on clinical trials showing the efficacy to reduce vertebral and non-vertebral fractures, strontium ranelate (SrR) has been approved in several countries for the treatment of postmenopausal osteoporosis. Hence, it is of special clinical interest to elucidate how the Sr uptake is influenced by dietary Ca deficiency as well as by the formula of Sr administration, SrR versus strontium chloride (SrCl(2)). Three-month-old ovariectomized rats were treated for 90 days with doses of 25 mg kg(-1) d(-1) and 150 mg kg(-1) d(-1) of SrR or SrCl(2) at low (0.1% Ca) or normal (1.19% Ca) Ca diet. Vertebral bone tissue was analysed by confocal synchrotron-radiation-induced micro X-ray fluorescence and by backscattered electron imaging. Principal component analysis and k-means clustering of the acquired elemental maps of Ca and Sr revealed that the newly formed bone exhibited the highest Sr fractions and that low Ca diet increased the Sr uptake by a factor of three to four. Furthermore, Sr uptake in bone of the SrCl(2)-treated animals was generally lower compared with SrR. The study clearly shows that inadequate nutritional calcium intake significantly increases uptake of Sr in serum as well as in trabecular bone matrix. This indicates that nutritional calcium intake as well as serum Ca levels are important regulators of any Sr treatment.

  7. Fine scale spatial genetic structure in Pouteria reticulata (Engl. Eyma (Sapotaceae, a dioecious, vertebrate dispersed tropical rain forest tree species

    Directory of Open Access Journals (Sweden)

    John W. Schroeder


    Full Text Available Dioecious tropical tree species often have small flowers and fleshy fruits indicative of small-insect pollination and vertebrate seed dispersal. We hypothesize that seed mediated gene flow should be exceed pollen-mediated gene flow in such species, leading to weak patterns of fine scale spatial genetic structure (SGS. In the present study, we characterize novel microsatellite DNA markers and test for SGS in sapling (N=100 and adult trees (N=99 of the dioecious canopy tree Pouteria reticulata (Sapotaceae in a 50 ha forest dynamics plot on Barro Colorado Island (BCI, Panama. The five genetic markers contained between five and 15 alleles per locus, totaling 51 alleles in the sample population. Significant SGS at local spatial scales (<100m was detected in the sapling (dbh≈1cm and adult (dbh≥20cm size classes, but was stronger in the former (sapling Sp=0.010±0.004, adult Sp=0.006±0.002, suggesting demographic thinning. The degree of SGS was lower than the value expected for non-vertebrate dispersed tropical trees (Sp=0.029, but similar to the average value for vertebrate dispersed tropical trees (Sp=0.009 affirming the dispersal potential of vertebrate dispersed tropical trees in faunally intact forests.

  8. The Chinese skeleton: insights into microstructure that help to explain the epidemiology of fracture. (United States)

    Cong, Elaine; Walker, Marcella D


    Osteoporotic fractures are a major public health problem worldwide, but incidence varies greatly across racial groups and geographic regions. Recent work suggests that the incidence of osteoporotic fracture is rising among Asian populations. Studies comparing areal bone mineral density and fracture across races generally indicate lower bone mineral density in Asian individuals including the Chinese, but this does not reflect their relatively low risk of non-vertebral fractures. In contrast, the Chinese have relatively high vertebral fracture rates similar to that of Caucasians. The paradoxically low risk for some types of fractures among the Chinese despite their low areal bone mineral density has been elucidated in part by recent advances in skeletal imaging. New techniques for assessing bone quality non-invasively demonstrate that the Chinese compensate for smaller bone size by differences in hip geometry and microstructural skeletal organization. Studies evaluating factors influencing racial differences in bone remodeling, as well as bone acquisition and loss, may further elucidate racial variation in bone microstructure. Advances in understanding the microstructure of the Chinese skeleton have not only helped to explain the epidemiology of fracture in the Chinese, but may also provide insight into the epidemiology of fracture in other races as well.

  9. The Tromsø study: registration of fractures, how good are self-reports, a computerized radiographic register and a discharge register? (United States)

    Joakimsen, R M; Fønnebø, V; Søgaard, A J; Tollan, A; Størmer, J; Magnus, J H


    In order to compare different methods of fracture registration, we sought all nonvertebral fractures suffered during 8 years (1988-95) among 21,441 persons invited to a survey in 1979/80. We registered a total of 54 hip fracture cases through three separate sources (self-report, computer linkage to the local radiographic archives, discharge register), whereas forearm fractures (a total of 291 cases) were registered through two separate sources (self-report, computer linkage to the radiographic archives). The registration of fractures at other sites (a total of 1321 cases) were from one source (computer linkage to the local radiographic archives), and we have compared three ways of obtaining data from this single source (no ascertainment, ascertainment of records coded as fracture, ascertainment of all records). Ninety-three percent of all hip fractures and 97% of all wrist fractures in the entire study population were found by computer linkage to the radiographic archives, whereas the discharge register detected 87% of all the hip fractures. Computer linkage with ascertainment gave no overreporting of fractures. Among the 11,626 persons who answered a follow-up questionnaire in 1994/95, 97% (CI 84-100%) of all hip fractures and 72% (CI 66-78%) of all wrist fractures were self-reported. We conclude that a computerized search of radiographic archives is a viable method of fracture registration.

  10. The Prevention of Postmenopausal Osteoporotic Fractures: Results of the Health Technology Assessment of a New Antiosteoporotic Drug

    Directory of Open Access Journals (Sweden)

    Chiara de Waure


    Full Text Available Objective. The Health Technology Assessment (HTA approach was applied to denosumab in the prevention of osteoporotic fractures in postmenopausal women. Method. Epidemiological, clinical, technical, economic, organizational, and ethical aspects were considered. Medical electronic databases were accessed to evaluate osteoporosis epidemiology and therapeutical approaches. A budget impact and a cost-effectiveness analyses were performed to assess economic implications. Clinical benefits and patient needs were considered with respect to organizational and ethical evaluation. Results. In Italy around four millions women are affected by osteoporosis and have a higher risk for fractures with 70,000 women being hospitalized every year. Bisphosphonates and strontium ranelate are recommended as first line treatment for the prevention of osteoporotic fractures. Denosumab is effective in reducing vertebral, nonvertebral, and hip/femoral fractures with an advantage of being administered subcutaneously every six months. The budget impact analysis estimated a reduction in costs for the National Health Service with the introduction of denosumab. Furthermore, the economic analysis demonstrated that denosumab is cost-effective in comparison to oral bisphosphonates and strontium ranelate. Denosumab can be administered in outpatients by involving General Practitioners in the management. Ethical evaluation is positive because of its efficacy and compliance. Conclusion. Denosumab could add value in the prevention of osteoporotic fractures.

  11. Hormone replacement therapy and the prevention of postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    Marco Gambacciani


    Full Text Available Fracture prevention is one of the public health priorities worldwide. Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis, the most common metabolic bone disease. Different effective treatments for osteoporosis are available. Hormone replacement therapy (HRT at different doses rapidly normalizes turnover, preserves bone mineral density (BMD at all skeletal sites, leading to a significant, reduction in vertebral and non-vertebral fractures. Tibolone, a selective tissue estrogenic activity regulator (STEAR, is effective in the treatment of vasomotor symptoms, vaginal atrophy and prevention/treatment of osteoporosis with a clinical efficacy similar to that of conventional HRT. Selective estrogen receptor modulators (SERMs such as raloxifene and bazedoxifene reduce turnover and maintain or increase vertebral and femoral BMD and reduce the risk of osteoporotic fractures. The combination of bazedoxifene and conjugated estrogens, defined as tissue selective estrogen complex (TSEC, is able to reduce climacteric symptoms, reduce bone turnover and preserve BMD. In conclusion, osteoporosis prevention can actually be considered as a major additional benefit in climacteric women who use HRT for treatment of climacteric symptoms. The use of a standard dose of HRT for osteoporosis prevention is based on biology, epidemiology, animal and preclinical data, observational studies and randomized, clinical trials. The antifracture effect of a lower dose HRT or TSEC is supported by the data on BMD and turnover, with compelling scientific evidence.

  12. zPicture: Dynamic Alignment and Visualization Tool for Analyzing Conservation Profiles

    Energy Technology Data Exchange (ETDEWEB)

    Ovcharenko, I. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Energy, Environment and Institutional Computing; Genome Biology Division; Loots, G. G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Genome Biology Division; Hardison, R. C. [Pennsylvania State Univ., Univ. Park, PA (United States). Dept. of Computer Science and Engineering; Miller., W. [Pennsylvania State Univ., Univ. Park, PA (United States). Dept. of Computer Science and Engineering; Dept. of Biology; Stubbs, L. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Genome Biology Division


    Comparative sequence analysis has evolved as an essential technique for identifying functional coding and noncoding elements conserved throughout evolution. Here we introduce zPicture (, an interactive web-based sequence alignment and visualization tool for dynamically generating conservation profiles and identifying evolutionary conserved regions (ECRs). zPicture is highly flexible because critical parameters can be modified interactively, allowing users to differentially predict ECRs in comparisons of sequences of different phylogenetic distances and evolutionary rates. We demonstrate the application of this module to identify a known regulatory element in the HOXD locus, where functional ECRs are difficult to discern against the highly conserved genomic background. zPicture also facilitates transcription factor binding site analysis via the rVISTA tool portal. We present an example of the HBB complex when zPicture/rVista combination specifically pinpoints to two ECRs containing GATA- 1, NF-E2 and TAL1/E47 binding sites that were previously identified as transcriptional enhancers. In addition, zPicture is linked to the UCSC Genome Browser allowing users to automatically extract sequences and gene annotations for any recorded locus. Finally, we describe how this tool can be efficiently applied to the analysis of nonvertebrate genomes including those of microbial organisms.

  13. The role of rank-ligand inhibition in the treatment of postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    M. Varenna


    Full Text Available Osteoporosis is a skeletal disease affecting millions of people worldwide in which a decreased bone mass and a microarchitectural deterioration compromise bone strength leading to bone fragility and increased susceptibility to fracture. Bone turnover increases at menopause, with osteoclast-mediated bone resorption exceeding bone formation. Recent discoveries in bone biology have demonstrated that RANKL, a cytokine member of the tumor necrosis factor superfamily, is an essential mediator of osteoclast formation, function and survival. Denosumab is a fully human monoclonal antibody with a high affinity and specificity for human RANKL. By binding to its target, denosumab prevents the interaction of RANKL with its receptor RANK on osteoclasts and their precursors and inhibits osteoclast-mediated bone resorption. Administered as a subcutaneous injection every six months, denosumab has been shown to decrease bone turnover and to increase bone mineral density in postmenopausal women with low bone mass and osteoporosis. In these patients denosumab significantly reduced the risk of vertebral fractures, hip fractures and nonvertebral fractures. In all clinical trials published to date, denosumab was well tolerated with an incidence of adverse events, including infections and malignancy, generally similar to subjects receiving placebo or alendronate. The denosumab therapeutic regimen consisting in a subcutaneous injection every 6 months may increase patient compliance and persistence with a further benefit from treatment. By providing a new molecular target for osteoporosis treatment, denosumab is a promising drug for the treatment of postmenopausal osteoporosis and the prevention of fragility fractures.

  14. Update on the efficacy, safety, and adherence to treatment of full length parathyroid hormone, PTH (1-84, in the treatment of postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    Luca Pietrogrande


    Full Text Available Luca PietrograndeDipartimento di Medicina Chirurgia e Odontoiatria Polo San Paolo, Università degli Studi di Milano, Milan, ItalyAbstract: Full length (1-84 parathyroid hormone (PTH was introduced in Europe as a treatment for postmenopausal osteoporosis in 2006. The efficacy of PTH (1-84 in the prevention of vertebral fractures is very high, and is similar to that of teriparatide. Its action in the prevention of femoral fractures has yet to be fully demonstrated, but the incidence of such fractures in trials was very low, and a decrease in nonvertebral fractures was seen in high-risk patients. The effect on bone mineral density (BMD was clearly demonstrated in the spine and also in the hip. The effects on BMD were evident and increased progressively with treatment until 36 months. After its discontinuation there was a clear decrease in BMD if no antiresorptive treatment was initiated. Increases in bone volumetric density and bone volume in trabecular sites were also reported. Moreover, a bone volume increase was detected in cortical sites. Hypercalcemia and hypercalciuria are frequent consequences of PTH treatment, but rarely have clinical effects and are usually well controlled by reducing calcium and vitamin D supplementation.Keywords: PTH (1-84, full-length parathyroid hormone, osteoporosis treatment

  15. [The role of rank-ligand inhibition in the treatment of postmenopausal osteoporosis]. (United States)

    Varenna, M; Gatti, D


    Osteoporosis is a skeletal disease affecting millions of people worldwide in which a decreased bone mass and a microarchitectural deterioration compromise bone strength leading to bone fragility and increased susceptibility to fracture. Bone turnover increases at menopause, with osteoclast-mediated bone resorption exceeding bone formation. Recent discoveries in bone biology have demonstrated that RANKL, a cytokine member of the tumor necrosis factor superfamily, is an essential mediator of osteoclast formation, function and survival. Denosumab is a fully human monoclonal antibody with a high affinity and specificity for human RANKL. By binding to its target, denosumab prevents the interaction of RANKL with its receptor RANK on osteoclasts and their precursors and inhibits osteoclast-mediated bone resorption. Administered as a subcutaneous injection every six months, denosumab has been shown to decrease bone turnover and to increase bone mineral density in postmenopausal women with low bone mass and osteoporosis. In these patients denosumab significantly reduced the risk of vertebral fractures, hip fractures and nonvertebral fractures. In all clinical trials published to date, denosumab was well tolerated with an incidence of adverse events, including infections and malignancy, generally similar to subjects receiving placebo or alendronate. The denosumab therapeutic regimen consisting in a subcutaneous injection every 6 months may increase patient compliance and persistence with a further benefit from treatment. By providing a new molecular target for osteoporosis treatment, denosumab is a promising drug for the treatment of postmenopausal osteoporosis and the prevention of fragility fractures.

  16. p63 in Mytilus galloprovincialis and p53 family members in the phylum Mollusca. (United States)

    Stifanić, Mauro; Micić, Milena; Ramsak, Andreja; Blasković, Sanja; Ruso, Ana; Zahn, Rudolf K; Batel, Renato


    Genes of the p53 family are known to be critical regulators of the cell cycle. They have already been established as possible biomarkers. Elaborate regulation mechanisms result in numerous cDNA and protein isoforms being expressed from each gene of the p53 family. Their similarity caused an often misleading nomenclature in non-vertebrate species. The aim of the present work is a clarification of the nomenclature of molluscan p53 family sequences, an essential prerequisite for reliable interpretation of gene expression and protein function studies. Here, we report five partial cDNA and one partial genomic p63 sequences, all originating from two Mytilus galloprovincialis individuals. DNA, deduced protein sequences, and the exon/intron architecture were analyzed and compared to p53, p63 and p73 sequences from other organisms. Along with our sequences, we analyzed all similar molluscan sequences found in the GenBank database. The analysis showed our cDNA sequences code for the TAp63gamma isoform of the p63 protein, and identified all other molluscan p53 family sequences as p63 genes or their expression isoforms. Our results also indicate p63 as the ancestral gene of the p53 family as well as the only gene of the family present in non-chordate metazoan species.

  17. Extending the family table: Insights from beyond vertebrates into the regulation of embryonic development by FGFs. (United States)

    Tulin, Sarah; Stathopoulos, Angelike


    Since the discovery of fibroblast growth factors (FGFs) much focus has been placed on elucidating the roles for each vertebrate FGF ligand, receptor, and regulating molecules in the context of vertebrate development, human disorders and cancer. Studies in human, mouse, frog, chick, and zebrafish have made great contributions to our understanding of the role of FGFs in specific processes. However, in recent years, as more genomes are sequenced, information is becoming available from many non-vertebrate models and a more complete picture of the FGF superfamily as a whole is emerging. In some cases, less redundancy in these FGF signaling systems may allow for more mechanistic insights. Studies in sea anemones have highlighted how ancient FGF signaling is and helped provide insight into the evolution of the FGF gene family. Work in nematodes has shown that different splice forms can be used for functional specificity in invertebrate FGF signaling. Comparing FGFs between urochordates and vertebrates as well as between different insect species reveals important clues into the process of gene loss, duplication and subfunctionalization of FGFs throughout evolution. Finally, comparing all members of the FGF ligand superfamily reveals variability in many properties, which may point to a feature of FGFs as being highly adaptable with regards to protein structure and signaling mechanism. Further studies on FGF signaling outside of vertebrates is likely to continue to complement work in vertebrates by contributing additional insights to the FGF field and providing unexpected information that could be used for medical applications.

  18. The Chinese skeleton:insights into microstructure that help to explain the epidemiology of fracture

    Institute of Scientific and Technical Information of China (English)

    Elaine Cong; Marcella D.Walker


    Osteoporotic fractures are a major public health problem worldwide, but incidence varies greatly across racial groups and geographic regions. Recent work suggests that the incidence of osteoporotic fracture is rising among Asian populations. Studies comparing areal bone mineral density and fracture across races generally indicate lower bone mineral density in Asian individuals including the Chinese, but this does not reflect their relatively low risk of non-vertebral fractures. In contrast, the Chinese have relatively high vertebral fracture rates similar to that of Caucasians. The paradoxically low risk for some types of fractures among the Chinese despite their low areal bone mineral density has been elucidated in part by recent advances in skeletal imaging. New techniques for assessing bone quality non-invasively demonstrate that the Chinese compensate for smaller bone size by differences in hip geometry and microstructural skeletal organization. Studies evaluating factors influencing racial differences in bone remodeling, as well as bone acquisition and loss, may further elucidate racial variation in bone microstructure. Advances in understanding the microstructure of the Chinese skeleton have not only helped to explain the epidemiology of fracture in the Chinese, but may also provide insight into the epidemiology of fracture in other races as well.

  19. Update on Denosumab Treatment in Postmenopausal Women with Osteoporosis

    Directory of Open Access Journals (Sweden)

    Yong-Ki Min


    Full Text Available Denosumab, a fully human recombinant monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL, blocks binding of RANKL to the RANK receptor, found on the surface of osteoclasts and osteoclast precursors, resulting in decreased bone resorption. Subcutaneous denosumab administration once every 6 months increases bone mineral density at the lumbar spine, total hip, and/or femoral neck, and reduces markers of bone turnover significantly in postmenopausal women with osteoporosis. Relative to placebo, denosumab treatment reduces the risk of vertebral, nonvertebral, and hip fractures significantly. The benefits of denosumab treatment are generally obvious after the first dose and were continued for up to 8 years of treatment in an extension study. The tolerability profile of denosumab during this extension phase was consistent with that observed during the initial 3-year FREEDOM trial. Postmarketing safety surveillance has not shown any unexpected findings. Ongoing safety surveillance will more fully define the long-term safety of denosumab. The benefits of denosumab would seem to be greater than its risks. Denosumab is an important choice in the treatment of postmenopausal women with osteoporosis at increased risk of fractures, including older patients who have difficulty with oral bisphosphonate intake and patients who are intolerant of, or unresponsive to, other therapies.

  20. Ontology for the asexual development and anatomy of the colonial chordate Botryllus schlosseri.

    Directory of Open Access Journals (Sweden)

    Lucia Manni

    Full Text Available Ontologies provide an important resource to integrate information. For developmental biology and comparative anatomy studies, ontologies of a species are used to formalize and annotate data that are related to anatomical structures, their lineage and timing of development. Here, we have constructed the first ontology for anatomy and asexual development (blastogenesis of a bilaterian, the colonial tunicate Botryllus schlosseri. Tunicates, like Botryllus schlosseri, are non-vertebrates and the only chordate taxon species that reproduce both sexually and asexually. Their tadpole larval stage possesses structures characteristic of all chordates, i.e. a notochord, a dorsal neural tube, and gill slits. Larvae settle and metamorphose into individuals that are either solitary or colonial. The latter reproduce both sexually and asexually and these two reproductive modes lead to essentially the same adult body plan. The Botryllus schlosseri Ontology of Development and Anatomy (BODA will facilitate the comparison between both types of development. BODA uses the rules defined by the Open Biomedical Ontologies Foundry. It is based on studies that investigate the anatomy, blastogenesis and regeneration of this organism. BODA features allow the users to easily search and identify anatomical structures in the colony, to define the developmental stage, and to follow the morphogenetic events of a tissue and/or organ of interest throughout asexual development. We invite the scientific community to use this resource as a reference for the anatomy and developmental ontology of B. schlosseri and encourage recommendations for updates and improvements.

  1. Antiresorptive drugs beyond bisphosphonates and selective oestrogen receptor modulators for the management of postmenopausal osteoporosis. (United States)

    Reginster, J Y; Neuprez, A; Beaudart, C; Lecart, M P; Sarlet, N; Bernard, D; Disteche, S; Bruyere, O


    Osteoporotic fractures are a major cause of morbidity in the elderly population. Since postmenopausal osteoporosis is related to an increase in osteoclastic activity at the time of menopause, inhibitors of bone resorption have genuinely been considered an adequate strategy for prevention and treatment of osteoporosis. Bisphosphonates and selective oestrogen receptor modulators are widely prescribed to treat osteoporosis. However, other antiresorptive drugs have been developed for the management of osteoporosis, with the objective of providing a substantial reduction in osteoporotic fractures at all skeletal sites, combined with an acceptable long-term skeletal and systemic safety profile. Denosumab, a human monoclonal antibody to receptor activator for nuclear factor kappa B ligand, has shown efficacy against vertebral, nonvertebral and hip fractures. Its administration every 6 months as a subcutaneous formulation might significantly influence compliance and persistence to therapy. Additional results regarding long-term skeletal safety (i.e. osteonecrosis of the jaw and atypical diaphyseal femoral fracture) are needed. Odanacatib, a selective cathepsin K inhibitor, is a promising new approach to the inhibition of osteoclastic resorption, with the potential to uncouple bone formation from bone resorption. Results regarding its anti-fracture efficacy are expected in the coming months.

  2. The inhibition of RANK-ligand in the management of postmenopausal osteoporosis and related fractures: the role of denosumab. (United States)

    Capozzi, Anna; Lello, Stefano; Pontecorvi, Alfredo


    There is great interest in new treatments of osteoporosis owing to general ageing of population and increased risk for fragility fractures in the elderly. Current therapies show a good efficacy in improving bone quality and bone density, but, in spite of a certain reduction in fracture rate, according to each treatment, the problem of osteoporotic fractures is yet far from to be solved. Moreover, some treatments may produce different side effects. Denosumab (Dmab), a receptor activator of nuclear factor kappa-B ligand (RANKL)-inhibitor, is an agent recently introduced in clinical practice for treatment of osteoporosis of postmenopausal women. Dmab has improved bone mineral density and prevented new vertebral and non-vertebral fractures with a similar efficacy in comparison with alendronate. Many clinical studies showed Dmab produces also significant improvement versus placebo in bone quality as indicated by decreasing markers of bone turnover. Patients using Dmab reported less risk of AFF (Atypical Femoral Fractures) and ONJ (Osteonecrosis of the Jaw) with an increased number of cellulitis. Here, we review articles using Dmab for female post-menopausal osteoporosis.

  3. Osteoporosis in Parkinson's disease. (United States)

    Invernizzi, Marco; Carda, Stefano; Viscontini, Giovanni Sguazzini; Cisari, Carlo


    Patients affected by Parkinson's disease are at a high risk for fractures, mainly of the hip. These fractures are caused by falls due to postural imbalance, neurological impairment and reduced bone mass. The purpose of this study was (1) to investigate the correlations and the pathophysiological mechanisms underlying bone loss in Parkinson's disease and appraise bone loss or fracture risk reduction interventions; (2) to develop a research agenda that informs the design and development of risk reduction strategies. Osteoporosis and osteopenia are very common findings in patients with Parkinson's disease, affecting up to 91% of women and 61% of men. Reduced bone mass in Parkinsonian patients seems to be caused mainly by reduced mobility through a mechanism similar to that observed in other neurological diseases. Endocrine (such as vitamin D deficiency), nutritional and iatrogenic factors also play an important role in bone mass depletion. Female gender, disease duration and severity (Hoehn and Yahr stages III and IV), old age and low body mass index are related to more severe osteoporosis. Vitamin D supplementation and bisphosphonates seem to be effective in reducing the risk of nonvertebral fractures in patients affected by Parkinson's disease. Prevention and evaluation of osteoporosis through bone mass density assessment should be considered in all patients with Parkinson's disease.

  4. Evolution of the relaxin/insulin-like gene family in placental mammals: implications for its early evolution. (United States)

    Hoffmann, Federico G; Opazo, Juan C


    The relaxin (RLN) and insulin-like (INSL) gene family is a group of genes involved in a variety of physiological roles that includes bone formation, testicular descent, trophoblast development, and cell differentiation. This family appears to have expanded in vertebrates relative to non-vertebrate chordates, but the relative contribution of whole genome duplications (WGDs) and tandem duplications to the observed diversity of genes is still an open question. Results from our comparative analyses favor a model of divergence post vertebrate WGDs in which a single-copy progenitor found in the last common ancestor of vertebrates experienced two rounds of WGDs before the functional differentiation that gave rise to the RLN and INSL genes. One of the resulting paralogs was subsequently lost, resulting in three proto-RLN/INSL genes on three separate chromosomes. Subsequent rounds of tandem gene duplication and divergence originated the set of paralogs found on a given cluster in extant vertebrates. Our study supports the hypothesis that differentiation of the RLN and INSL genes took place independently in each RLN/INSL cluster after the two WGDs during the evolutionary history of vertebrates. In addition, we show that INSL4 represents a relatively old gene that has been apparently lost independently in all Euarchontoglires other than apes and Old World monkeys, and that RLN2 derives from an ape-specific duplication.

  5. Does hybridization increase evolutionary rate? Data from the 28S-rDNA D8 domain in echinoderms. (United States)

    Chenuil, Anne; Egea, Emilie; Rocher, Caroline; Touzet, Hélène; Féral, Jean-Pierre


    The divergent domain D8 of the large ribosomal RNA is very variable and extended in vertebrates compared to other eukaryotes. We provide data from 31 species of echinoderms and present the first comparative analysis of the D8 in nonvertebrate deuterostomes. In addition, we obtained 16S mitochondrial DNA sequences for the sea urchin taxa and analyzed single-strand conformation polymorphism (SSCP) of D8 in several populations within the species complex Echinocardium cordatum. A common secondary structure supported by compensatory substitutions and indels is inferred for echinoderms. Variation mostly arises at the tip of the longest stem (D8a), and the most variable taxa also display the longest and most stable D8. The most stable variants are the only ones displaying bulges in the terminal part of the stem, suggesting that selection, rather than maximizing stability of the D8 secondary structure, maintains it in a given range. Striking variation in D8 evolutionary rates was evidenced among sea urchins, by comparison with both 16S mitochondrial DNA and paleontological data. In Echinocardium cordatum and Strongylocentrotus pallidus and S. droebachiensis, belonging to very distant genera, the increase in D8 evolutionary rate is extreme. Their highly stable D8 secondary structures rule out the possibility of pseudogenes. These taxa are the only ones in which interspecific hybridization was reported. We discuss how evolutionary rates may be affected in nuclear relative to mitochondrial genes after hybridization, by selective or mutational processes such as gene silencing and concerted evolution.

  6. Molecular and functional properties of P2X receptors--recent progress and persisting challenges. (United States)

    Kaczmarek-Hájek, Karina; Lörinczi, Eva; Hausmann, Ralf; Nicke, Annette


    ATP-gated P2X receptors are trimeric ion channels that assemble as homo- or heteromers from seven cloned subunits. Transcripts and/or proteins of P2X subunits have been found in most, if not all, mammalian tissues and are being discovered in an increasing number of non-vertebrates. Both the first crystal structure of a P2X receptor and the generation of knockout (KO) mice for five of the seven cloned subtypes greatly advanced our understanding of their molecular and physiological function and their validation as drug targets. This review summarizes the current understanding of the structure and function of P2X receptors and gives an update on recent developments in the search for P2X subtype-selective ligands. It also provides an overview about the current knowledge of the regulation and modulation of P2X receptors on the cellular level and finally on their physiological roles as inferred from studies on KO mice.

  7. Lipoprotein-like particles in a prokaryote: quinone droplets of Thermoplasma acidophilum. (United States)

    Nagy, István; Knispel, Roland Wilhelm; Kofler, Christine; Orsini, Massimiliano; Boicu, Marius; Varga, Sándor; Weyher-Stingl, Elisabeth; Sun, Na; Fernandez-Busnadiego, Ruben; Kukolya, József; Nickell, Stephan; Baumeister, Wolfgang


    Cytosolic, globular droplets with an average diameter of 50 nm were observed in vitrified Thermoplasma acidophilum cells by means of cryo-electron tomography. These droplets were isolated by column chromatography and immunoprecipitation protein purification methods. Subsequent chemical and biochemical analyses identified lipid and protein components, respectively. Two major lipid components, comigrating menaquinones at the solvent front and the slower migrating Thermoplasma polar lipid U4, were detected by TLC experiments. The major protein component was identified as the 153 amino acid long Ta0547 vitellogenin-N domain protein. This domain has been found so far exclusively in large lipid transport proteins of vertebrates and non-vertebrates. Blast protein database homology searches with Ta0547 did not return any eukaryal hits; homologous sequences were found only in thermo-acidophilic archaeons. However, a profile-sequence domain search performed with the vitellogenin-N domain (PF01347) hmm-profile against the T. acidophilum proteome returned Ta0547 as hit. Electron microscopy appearance of isolated droplets resembled to lipoprotein particles. However, no (tetraether) lipid layer could be detected on the droplets surface, rather hydrophobic compounds of the electron dense lumen were surrounded by a denser discontinuous protein boundary. Based on described features, these particles qualify for a novel lipoprotein particle category, what we nominated Thermoplasma Quinone Droplet.

  8. Growth and Age-Related Abnormalities in Cortical Structure and Fracture Risk

    Directory of Open Access Journals (Sweden)

    Ego Seeman


    Full Text Available Vertebral fractures and trabecular bone loss have dominated thinking and research into the pathogenesis and the structural basis of bone fragility during the last 70 years. However, 80% of all fractures are non-vertebral and occur at regions assembled using large amounts of cortical bone; only 20% of fractures are vertebral. Moreover, ~80% of the skeleton is cortical and ~70% of all bone loss is cortical even though trabecular bone is lost more rapidly than cortical bone. Bone is lost because remodelling becomes unbalanced after midlife. Most cortical bone loss occurs by intracortical, not endocortical remodelling. Each remodelling event removes more bone than deposited enlarging existing canals which eventually coalesce eroding and thinning the cortex from 'within.' Thus, there is a need to study the decay of cortical as well as trabecular bone, and to develop drugs that restore the strength of both types of bone. It is now possible to accurately quantify cortical porosity and trabecular decay in vivo. The challenges still to be met are to determine whether measurement of porosity identifies persons at risk for fracture, whether this approach is compliments information obtained using bone densitometry, and whether changes in cortical porosity and other microstructural traits have the sensitivity to serve as surrogates of treatment success or failure.

  9. Association of collagen type I alpha1 (COLIA1) Sp1 polymorphism with osteoporotic fracture in Caucasian post-menopausal women: a meta-analysis.

    LENUS (Irish Health Repository)

    Ji, G-R


    This study was designed to summarize quantitatively the evidence for a relationship between collagen type I alpha1 (COLIA1) Sp1 polymorphism and osteoporotic fracture risk in Caucasian post-menopausal women. This meta-analysis included 16 studies, which analysed 2294 patients with fractures and 10 285 controls. The combined results showed that there was a significant difference in genotype distribution (SS odds ratio [OR] 0.72; Ss OR 1.18; ss OR 1.97) between patients with fractures and controls. When stratifying by the fracture site, it was found that: (i) patients with vertebral fractures had a significantly higher frequency of the Ss genotype and a lower frequency of the SS genotype than controls; and (ii) patients with non-vertebral fractures had a significantly higher frequency of the ss genotype and a lower frequency of the SS genotype than controls. This meta-analysis suggests that the COLIA1 Sp1 polymorphism may be associated with osteoporotic fracture in Caucasian post-menopausal women.

  10. Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management

    Directory of Open Access Journals (Sweden)

    Luca Dalle Carbonare


    Full Text Available Luca Dalle Carbonare, Mirko Zanatta, Adriano Gasparetto, Maria Teresa ValentiClinic of Internal Medicine D, Department of Medicine, University of Verona, ItalyAbstract: Bisphosphonates (BPs are widely used in the treatment of postmenopausal ­osteoporosis and other metabolic bone diseases. They bind strongly to bone matrix and reduce bone loss through inhibition of osteoclast activity. They are classified as nitrogen- and non-nitrogen-containing bisphosphonates (NBPs and NNBPs, respectively. The former inhibit farnesyl diphosphate synthase while the latter induce the production of toxic analogs of adenosine triphosphate. These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action. Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation. Several randomized control trials have demonstrated that NBPs significantly improve bone mineral density, suppress bone turnover, and reduce the incidence of both vertebral and nonvertebral fragility fractures. Although they are generally considered safe, some side effects are reported (esophagitis, acute phase reaction, hypocalcemia, uveitis, and compliance with therapy is often inadequate. In particular, gastrointestinal discomfort is frequent with the older daily oral administrations and is responsible for a high proportion of discontinuation. The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes.Keywords: bisphosphonates, osteoporosis, safety, tolerability, zoledronic acid

  11. Alendronate prevents glucocorticoid-induced osteoporosis in patients with rheumatic diseases: A meta-analysis. (United States)

    Kan, Shun-Li; Yuan, Zhi-Fang; Li, Yan; Ai, Jie; Xu, Hong; Sun, Jing-Cheng; Feng, Shi-Qing


    Glucocorticoid-induced osteoporosis (GIOP) is a serious problem for patients with rheumatic diseases requiring long-term glucocorticoid treatment. Alendronate, a bisphosphonate, has been recommended in the prevention of GIOP. However, the efficacy and safety of alendronate in preventing GIOP remains controversial. We performed a meta-analysis to investigate the efficacy and safety of alendronate in preventing GIOP in patients with rheumatic diseases.We retrieved randomized controlled trials from PubMed, EMBASE, and the Cochrane Library. Two reviewers extracted the data and evaluated the risk of bias and quality of the evidence. We calculated the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes, and the mean difference (MD) with a 95% CI for continuous outcomes using Review Manager, version 5.3.A total of 339 studies were found, and 9 studies (1134 patients) were included. Alendronate was not able to reduce the incidence of vertebral fractures (RR = 0.63, 95% CI: 0.10-4.04, P = 0.62) and nonvertebral fractures (RR = 0.40, 95% CI: 0.15-1.12, P = 0.08). Alendronate significantly increased the percent change in bone mineral density (BMD) at the lumbar spine (MD = 3.66, 95% CI: 2.58-4.74, P power.

  12. Denosumab for the management of postmenopausal osteoporosis. (United States)

    Singer, Andrea; Grauer, Andreas


    View the National Osteoporosis Foundation Clinician's Guide Postmenopausal osteoporosis is a major concern to public health. Fractures are the major clinical consequence of osteoporosis and are associated with substantial morbidity, mortality, and health care costs. Despite the availability of screening and treatment guidelines, osteoporosis diagnosis and treatment remain low. Health care providers may consult guidelines in the clinical management of their patients with osteoporosis, including those from the National Osteoporosis Foundation, and the new fracture risk assessment tool from the World Health Organization. Bisphosphonates are the most commonly used treatment for postmenopausal osteoporosis. Although these agents are effective in preventing fractures and bone loss, the benefits of treatment may be limited by suboptimal adherence and compliance. Denosumab is a human monoclonal antibody that targets and inhibits RANK ligand, an essential mediator of bone resorption. In clinical trials in postmenopausal women with osteoporosis, denosumab 60 mg given subcutaneously every 6 months was well tolerated and statistically significantly reduced the risk of vertebral, nonvertebral, and hip fractures. The introduction of denosumab into clinical practice provides physicians with another option for the treatment of postmenopausal osteoporosis, and the twice-yearly dosing regimen has the potential to improve adherence.

  13. There is no universal molecular clock for invertebrates, but rate variation does not scale with body size. (United States)

    Thomas, Jessica A; Welch, John J; Woolfit, Megan; Bromham, Lindell


    The existence of a universal molecular clock has been called into question by observations that substitution rates vary widely between lineages. However, increasing empirical evidence for the systematic effects of different life history traits on the rate of molecular evolution has raised hopes that rate variation may be predictable, potentially allowing the "correction" of the molecular clock. One such example is the body size trend observed in vertebrates; smaller species tend to have faster rates of molecular evolution. This effect has led to the proposal of general predictive models correcting for rate heterogeneity and has also been invoked to explain discrepancies between molecular and paleontological dates for explosive radiations in the fossil record. Yet, there have been no tests of an effect in any nonvertebrate taxa. In this study, we have tested the generality of the body size effect by surveying a wide range of invertebrate metazoan lineages. DNA sequences and body size data were collected from the literature for 330 species across five phyla. Phylogenetic comparative methods were used to investigate a relationship between average body size and substitution rate at both interspecies and interfamily comparison levels. We demonstrate significant rate variation in all phyla and most genes examined, implying a strict molecular clock cannot be assumed for the Metazoa. Furthermore, we find no evidence of any influence of body size on invertebrate substitution rates. We conclude that the vertebrate body size effect is a special case, which cannot be simply extrapolated to the rest of the animal kingdom.

  14. Characteristic and functional analysis of toll-like receptors (TLRs in the lophotrocozoan, Crassostrea gigas, reveals ancient origin of TLR-mediated innate immunity.

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    Yang Zhang

    Full Text Available The evolution of TLR-mediated innate immunity is a fundamental question in immunology. Here, we report the characterization and functional analysis of four TLR members in the lophotrochozoans Crassostreagigas (CgTLRs. All CgTLRs bear a conserved domain organization and have a close relationship with TLRs in ancient non-vertebrate chordates. In HEK293 cells, every CgTLR could constitutively activate NF-κB responsive reporter, but none of the PAMPs tested could stimulate CgTLR-activated NF-κB induction. Subcellular localization showed that CgTLR members have similar and dual distribution on late endosomes and plasma membranes. Moreover, CgTLRs and CgMyD88 mRNA show a consistent response to multiple PAMP challenges in oyster hemocytes. As CgTLR-mediated NF-κB activation is dependent on CgMyD88, we designed a blocking peptide for CgTLR signaling that would inhibit CgTLR-CgMyD88 dependent NF-κB activation. This was used to demonstrate that a Vibrio parahaemolyticus infection-induced enhancement of degranulation and increase of cytokines TNF mRNA in hemocytes, could be inhibited by blocking CgTLR signaling. In summary, our study characterized the primitive TLRs in the lophotrocozoan C. gigas and demonstrated a fundamental role of TLR signaling in infection-induced hemocyte activation. This provides further evidence for an ancient origin of TLR-mediated innate immunity.

  15. Comparative biology of the pentraxin protein family: evolutionarily conserved component of innate immune system. (United States)

    Armstrong, Peter B


    The immune system is based on the actions of the collection of specialized immune defense cells and their secreted proteins and peptides that defend the host against infection by parasites. Parasites are organisms that live part or all of their lives in close physical association with the host and extract nutrients from the host and, by releasing toxins and virulence factors, cause disease with the potential for injury and premature death of that host. Parasites of the metazoa can be viruses, eubacteria, fungi, protozoans, and other metazoans. The immune system operates to kill or eliminate parasites and eliminate or detoxify their toxins and virulence factors. Although some of the elements of immune systems are specific to a particular phylum of metazoans, others show extensive evolutionary conservation, being present in several or all major phyla of the metazoa. The pentraxins display this latter character in their roles in immune defense. Pentraxins have been documented in vertebrates, nonvertebrate chordates, arthropods, and mollusks and may be present in other taxa of metazoans. Presumably the pentraxins appeared early in the evolution of metazoa, prior to their evolutionary divergence in the Precambrian epoch into many phyla present today, and have been preserved for the 542 million years since that explosive evolutionary radiation. The fidelity with which these phyla have preserved the pentraxins suggests that the functions of these proteins are important for survival of the members of these diverse taxa of animals.

  16. Consciousness in humans and non-human animals: Recent advances and future directions.

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    Melanie eBoly


    Full Text Available This joint article reflects the authors’ personal views regarding noteworthy advances in the neuroscience of consciousness in the last ten years, and suggests what we feel may be promising future directions. It is based on a small conference at the Samoset Resort in Rockport, Maine, USA, in July of 2012, organized by the Mind Science Foundation of San Antonio, Texas. Here, we summarize recent advances in our understanding of subjectivity in humans and other animals, including empirical, applied, technical and conceptual insights. These include the evidence for the importance of fronto-parietal connectivity and of feedback processes, both of which enable information to travel across distant cortical areas effectively, as well as numerous dissociations between consciousness and cognitive functions, such as attention, in humans. In addition, we describe the development of mental imagery paradigms, which made it possible to identify covert awareness in non-responsive subjects. Non-human animal consciousness research has also witnessed substantial advances on the specific role of cortical areas and higher order thalamus for consciousness, thanks to important technological advances. In addition, much progress has been made in the understanding of non-vertebrate cognition relevant to possible conscious states. Finally, major advances have been made in theories of consciousness, and also in their comparison with the available evidence. Along with reviewing these findings, each author suggests future avenues for research in their field of investigation.

  17. The mitochondrial genome of Phallusia mammillata and Phallusia fumigata (Tunicata, Ascidiacea: high genome plasticity at intra-genus level

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    Pesole Graziano


    Full Text Available Abstract Background Within Chordata, the subphyla Vertebrata and Cephalochordata (lancelets are characterized by a remarkable stability of the mitochondrial (mt genome, with constancy of gene content and almost invariant gene order, whereas the limited mitochondrial data on the subphylum Tunicata suggest frequent and extensive gene rearrangements, observed also within ascidians of the same genus. Results To confirm this evolutionary trend and to better understand the evolutionary dynamics of the mitochondrial genome in Tunicata Ascidiacea, we have sequenced and characterized the complete mt genome of two congeneric ascidian species, Phallusia mammillata and Phallusia fumigata (Phlebobranchiata, Ascidiidae. The two mtDNAs are surprisingly rearranged, both with respect to one another and relative to those of other tunicates and chordates, with gene rearrangements affecting both protein-coding and tRNA genes. The new data highlight the extraordinary variability of ascidian mt genome in base composition, tRNA secondary structure, tRNA gene content, and non-coding regions (number, size, sequence and location. Indeed, both Phallusia genomes lack the trnD gene, show loss/acquisition of DHU-arm in two tRNAs, and have a G+C content two-fold higher than other ascidians. Moreover, the mt genome of P. fumigata presents two identical copies of trnI, an extra tRNA gene with uncertain amino acid specificity, and four almost identical sequence regions. In addition, a truncated cytochrome b, lacking a C-terminal tail that commonly protrudes into the mt matrix, has been identified as a new mt feature probably shared by all tunicates. Conclusion The frequent occurrence of major gene order rearrangements in ascidians both at high taxonomic level and within the same genus makes this taxon an excellent model to study the mechanisms of gene rearrangement, and renders the mt genome an invaluable phylogenetic marker to investigate molecular biodiversity and speciation

  18. A glycine receptor is involved in the organization of swimming movements in an invertebrate chordate

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    Okamura Yasushi


    Full Text Available Abstract Background Rhythmic motor patterns for locomotion in vertebrates are generated in spinal cord neural networks known as spinal Central Pattern Generators (CPGs. A key element in pattern generation is the role of glycinergic synaptic transmission by interneurons that cross the cord midline and inhibit contralaterally-located excitatory neurons. The glycinergic inhibitory drive permits alternating and precisely timed motor output during locomotion such as walking or swimming. To understand better the evolution of this system we examined the physiology of the neural network controlling swimming in an invertebrate chordate relative of vertebrates, the ascidian larva Ciona intestinalis. Results A reduced preparation of the larva consisting of nerve cord and motor ganglion generates alternating swimming movements. Pharmacological and genetic manipulation of glycine receptors shows that they are implicated in the control of these locomotory movements. Morphological molecular techniques and heterologous expression experiments revealed that glycine receptors are inhibitory and are present on both motoneurones and locomotory muscle while putative glycinergic interneurons were identified in the nerve cord by labeling with an anti-glycine antibody. Conclusions In Ciona intestinalis, glycine receptors, glycinergic transmission and putative glycinergic interneurons, have a key role in coordinating swimming movements through a simple CPG that is present in the motor ganglion and nerve cord. Thus, the strong association between glycine receptors and vertebrate locomotory networks may now be extended to include the phylum chordata. The results suggest that the basic network for 'spinal-like' locomotion is likely to have existed in the common ancestor of extant chordates some 650 M years ago.

  19. Gelsolin in Onychophora and Tardigrada with notes on its variability in the Ecdysozoa. (United States)

    Thiruketheeswaran, Prasath; Greven, Hartmut; D'Haese, Jochen


    Rearrangements of the filamentous actin network involve a broad range of actin binding proteins. Among these, the gelsolin proteins sever actin filaments, cap their fast growing end and nucleate actin assembly in a calcium-dependent manner. Here, we focus on the gelsolin of the onychophoran Peripatoides novaezealandiae and the eutardigrade Hypsibius dujardini. From the cDNA of P. novaezealandiae we obtained the complete coding sequence with an open reading frame of 2178bp. It encodes a protein of 726 amino acids with a calculated molecular mass of 82,610.9Da and a pI of 5.57. This sequence is comprised of six segments (S1-S6). However, analysis of data from TardiBase reveals that the gelsolin of the eutardigrade Hypsibius dujardini has only three segments (S1-S3). The coding sequence consist of 1119bp for 373 amino acids with a calculated molecular mass of 42,440.95Da and a pI of 6.17. The Peripatoides and Hypsibius gelsolin revealed both conserved binding motifs for G-actin, F-actin and phosphatidylinositol 4,5-bisphosphate (PIP2), along with a full set of type-1 and type-2 Ca(2+)-binding sites which could result in the binding of eight and four calcium ions, respectively. Both gelsolin proteins lack a C-terminal latch-helix indicating a more rapid activation in the submicromolar Ca(2+) range. We suggest that a gelsolin with three segments was present in the last common ancestor of the ecdysozoan clade Panarthropoda (Onychophora, Tardigrada, Arthropoda), primarily because the gelsolin of all non-Ecdysozoa studied so far (except Chordata) reveals this number of segments. Mapping of our molecular data onto a well-established phylogeny revealed that the number of gelsolin segments does not correlate with the phylogenetic lineage but rather with particular functional demands to alter the kinetics of actin polymerization.

  20. New insights on the sialidase protein family revealed by a phylogenetic analysis in metazoa.

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    Edoardo Giacopuzzi

    Full Text Available Sialidases are glycohydrolytic enzymes present from virus to mammals that remove sialic acid from oligosaccharide chains. Four different sialidase forms are known in vertebrates: the lysosomal NEU1, the cytosolic NEU2 and the membrane-associated NEU3 and NEU4. These enzymes modulate the cell sialic acid content and are involved in several cellular processes and pathological conditions. Molecular defects in NEU1 are responsible for sialidosis, an inherited disease characterized by lysosomal storage disorder and neurodegeneration. The studies on the biology of sialic acids and sialyltransferases, the anabolic counterparts of sialidases, have revealed a complex picture with more than 50 sialic acid variants selectively present in the different branches of the tree of life. The gain/loss of specific sialoconjugates have been proposed as key events in the evolution of deuterostomes and Homo sapiens, as well as in the host-pathogen interactions. To date, less attention has been paid to the evolution of sialidases. Thus we have conducted a survey on the state of the sialidase family in metazoan. Using an in silico approach, we identified and characterized sialidase orthologs from 21 different organisms distributed among the evolutionary tree: Metazoa relative (Monosiga brevicollis, early Deuterostomia, precursor of Chordata and Vertebrata (teleost fishes, amphibians, reptiles, avians and early and recent mammals. We were able to reconstruct the evolution of the sialidase protein family from the ancestral sialidase NEU1 and identify a new form of the enzyme, NEU5, representing an intermediate step in the evolution leading to the modern NEU3, NEU4 and NEU2. Our study provides new insights on the mechanisms that shaped the substrate specificity and other peculiar properties of the modern mammalian sialidases. Moreover, we further confirm findings on the catalytic residues and identified enzyme loop portions that behave as rapidly diverging regions and may

  1. Functional assays and metagenomic analyses reveals differences between the microbial communities inhabiting the soil horizons of a Norway spruce plantation.

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    Stéphane Uroz

    Full Text Available In temperate ecosystems, acidic forest soils are among the most nutrient-poor terrestrial environments. In this context, the long-term differentiation of the forest soils into horizons may impact the assembly and the functions of the soil microbial communities. To gain a more comprehensive understanding of the ecology and functional potentials of these microbial communities, a suite of analyses including comparative metagenomics was applied on independent soil samples from a spruce plantation (Breuil-Chenue, France. The objectives were to assess whether the decreasing nutrient bioavailability and pH variations that naturally occurs between the organic and mineral horizons affects the soil microbial functional biodiversity. The 14 Gbp of pyrosequencing and Illumina sequences generated in this study revealed complex microbial communities dominated by bacteria. Detailed analyses showed that the organic soil horizon was significantly enriched in sequences related to Bacteria, Chordata, Arthropoda and Ascomycota. On the contrary the mineral horizon was significantly enriched in sequences related to Archaea. Our analyses also highlighted that the microbial communities inhabiting the two soil horizons differed significantly in their functional potentials according to functional assays and MG-RAST analyses, suggesting a functional specialisation of these microbial communities. Consistent with this specialisation, our shotgun metagenomic approach revealed a significant increase in the relative abundance of sequences related glycoside hydrolases in the organic horizon compared to the mineral horizon that was significantly enriched in glycoside transferases. This functional stratification according to the soil horizon was also confirmed by a significant correlation between the functional assays performed in this study and the functional metagenomic analyses. Together, our results suggest that the soil stratification and particularly the soil resource

  2. Breakdown of phylogenetic signal: a survey of microsatellite densities in 454 shotgun sequences from 154 non model eukaryote species.

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    Emese Meglécz

    Full Text Available Microsatellites are ubiquitous in Eukaryotic genomes. A more complete understanding of their origin and spread can be gained from a comparison of their distribution within a phylogenetic context. Although information for model species is accumulating rapidly, it is insufficient due to a lack of species depth, thus intragroup variation is necessarily ignored. As such, apparent differences between groups may be overinflated and generalizations cannot be inferred until an analysis of the variation that exists within groups has been conducted. In this study, we examined microsatellite coverage and motif patterns from 454 shotgun sequences of 154 Eukaryote species from eight distantly related phyla (Cnidaria, Arthropoda, Onychophora, Bryozoa, Mollusca, Echinodermata, Chordata and Streptophyta to test if a consistent phylogenetic pattern emerges from the microsatellite composition of these species. It is clear from our results that data from model species provide incomplete information regarding the existing microsatellite variability within the Eukaryotes. A very strong heterogeneity of microsatellite composition was found within most phyla, classes and even orders. Autocorrelation analyses indicated that while microsatellite contents of species within clades more recent than 200 Mya tend to be similar, the autocorrelation breaks down and becomes negative or non-significant with increasing divergence time. Therefore, the age of the taxon seems to be a primary factor in degrading the phylogenetic pattern present among related groups. The most recent classes or orders of Chordates still retain the pattern of their common ancestor. However, within older groups, such as classes of Arthropods, the phylogenetic pattern has been scrambled by the long independent evolution of the lineages.

  3. Macro- and megafauna recorded in the submarine Bari Canyon (southern Adriatic, Mediterranean Sea using different tools

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    Full Text Available Macro- and megafauna were recorded in the submarine Bari Canyon (southern Adriatic Sea, Mediterranean Sea during an oceanographic cruise carried out in May-June 2012 and an experimental fishing survey conducted in November 2013. During the former, a total of 20 benthic samples were taken using a Van Veen grab at depths between 268 and 770 m and 4 deployments of a baited lander, for about 43 hours of video records, were carried out at depths between 443 and 788 m. During the latter, 8 longline fishing operations were conducted from 338 down to 612 m. Eighty-five living benthic and benthopelagic species were recorded: 29 Porifera, 1 Cnidaria, 2 Mollusca, 11 Annelida, 1 Arthropoda, 19 Bryozoa, 3 Echinodermata and 19 Chordata. A total of 51 species are new records for the Bari Canyon, 29 new records for the Adriatic Sea. Among the Porifera Cerbaris curvispiculifer is a new addition for the Italian Sponge Fauna. The first certain record of living specimens for the bryozoan Crisia tenella longinodata is reported. A total of 6 Mediterranean endemic species have been identified: 4 Porifera and 2 Annelida. The bathymetric range of some species has been extended. New information acquired for deep sea species confirms their importance in the structure of cold-water coral communities. This study has updated the knowledge on the biodiversity of the Adriatic Sea, as well as of the Bari Canyon in particular, one of the sites designated as “jewels of the Mediterranean” for which urgent conservation measures are needed.

  4. Inter-annual variation (1991-1993) of the substratum-leaf colonization dynamics for aquatic fauna in different habitats of the lake of the hydroelectric of Balbina, Amazon Central, Brazil; Variacao interanual (1991-1993) da dinamica de colonizacao de substrato-folha por fauna aquatica, em diferentes habitats do lago da Hidreletrica de Balbina, Amazonia Central, Amazonas- Brasil

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    Vela-Pena, Gladys


    Experiments on fauna colonization of submersed vegetal substrate in different depths of water column were done to evaluate the benthic community structure in three habitats of the Balbina hydroelectric dam in 1991, 1992 and 1993. In these experiments substrate exposition periods of up to 60 and 75 days were done. The fauna associated to the standard substrate (Mabea caudata) belonged to seven phyla: Arthropoda, Coelenterata, Nematoda, Bryozoa, Annelida, Mollusca an Chordata. The most abundant and frequent families, during the studied period, were Naididae (Tubificida), Chydoridae (Cladocera) and Cenestheridae (Conchostraca), suggesting the persistence of these groups. In general, the pattern of colonization indicates some tendency to increase gradually with time of exposition of the substrate in the environment. Probably, the discontinuity of the tendencies is associated with the insects mobility and emergence. The initial colonization always was higher and quicker in the margin habitat, which indicates that the source of organisms is this habitat. This is due to better conditions of the environment such as availability of food and protection, associated with the submerged vegetation and wood. The community mean density during this study was 7, 312 ind/m{sup 2}. The density, the species richness index, and the diversity were correlated with abiotic variables such as pH, temperature, dissolved oxygen, habitat and depth. Also, the density was correlated with total carbon and ammonium. Species richness was correlated with total carbon, ammonium and water color. The density, diversity and species richness were proportionally inverse to depth of the habitats and total absence of organisms ago 10 meter of depth, different from what is found in bottom of natural environments. This fact was attributed to the high concentration of nutrients, such as ammonium and dissolved iron, to the existence of toxic gases such a sulphide, and to the conditions of hypoxia in the deep

  5. Comparative study on bioremediation of heavy metals by solitary ascidian, Phallusia nigra, between Thoothukudi and Vizhinjam ports of India. (United States)

    Abdul Jaffar Ali, H; Tamilselvi, M; Akram, A Soban; Kaleem Arshan, M L; Sivakumar, V


    Ascidians belonging to the sub-phylum Uro-chordata are used as potential model organisms in various parts of the world for biosorption of metals. The sedentary nature, filter feeding habits, presence of vanadocytes and the absence of kidneys cause them to accumulate metals. The present study was aimed to compare biosorption of metals such as cadmium, copper, lead, mercury and vanadium in test and mantle body of solitary ascidian Phallusia nigra between two ecologically significant stations such as Thoothukudi (Station 1) and Vizhinjam (Station 2) ports of India. Monthly samplings of water and P. nigra were done for a period of one year from September 2010 to August 2011 and subjected to analysis of metal accumulation. The average metal concentrations except mercury in the Thoothukudi water were found to be higher of comparable magnitudes than the Vizhinjam water. One-way ANOVA showed significant differences between the stations. A comparison of average metal concentrations in the test and mantle body of P. nigra between two stations showed that the enrichment of V, Cd, Pb, Cu and Hg in the Thoothukudi samples may be due to high bioaccumulation factors of these elements as compared to other species of ascidians. The bioaccumulation factors were in the order of V>Pb>Cd>Cu> Hg for the test and mantle body in stations 1 and 2. Application of one-way ANOVA for the concentration of these metals between test and mantle body showed significant differences in both stations. Similarly, ANOVA for biosorption of these trace metals by P. nigra showed significant difference between stations. Metal concentrations recorded in this ascidian could effectively be used as good reference material for monitoring metal contamination in Indian sea waters.

  6. The α1,6-fucosyltransferase gene (fut8 from the Sf9 lepidopteran insect cell line: insights into fut8 evolution.

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    Sylvie Juliant

    Full Text Available The core alpha1,6-fucosyltransferase (FUT8 catalyzes the transfer of a fucosyl moiety from GDP-fucose to the innermost asparagine-linked N-acetylglucosamine residue of glycoproteins. In mammals, this glycosylation has an important function in many fundamental biological processes and although no essential role has been demonstrated yet in all animals, FUT8 amino acid (aa sequence and FUT8 activity are very well conserved throughout the animal kingdom. We have cloned the cDNA and the complete gene encoding the FUT8 in the Sf9 (Spodoptera frugiperda lepidopteran cell line. As in most animal genomes, fut8 is a single-copy gene organized in different exons. The open reading frame contains 12 exons, a characteristic that seems to be shared by all lepidopteran fut8 genes. We chose to study the gene structure as a way to characterize the evolutionary relationships of the fut8 genes in metazoans. Analysis of the intron-exon organization in 56 fut8 orthologs allowed us to propose a model for fut8 evolution in metazoans. The presence of a highly variable number of exons in metazoan fut8 genes suggests a complex evolutionary history with many intron gain and loss events, particularly in arthropods, but not in chordata. Moreover, despite the high conservation of lepidoptera FUT8 sequences also in vertebrates and hymenoptera, the exon-intron organization of hymenoptera fut8 genes is order-specific with no shared exons. This feature suggests that the observed intron losses and gains may be linked to evolutionary innovations, such as the appearance of new orders.

  7. The α1,6-fucosyltransferase gene (fut8) from the Sf9 lepidopteran insect cell line: insights into fut8 evolution. (United States)

    Juliant, Sylvie; Harduin-Lepers, Anne; Monjaret, François; Catieau, Béatrice; Violet, Marie-Luce; Cérutti, Pierre; Ozil, Annick; Duonor-Cérutti, Martine


    The core alpha1,6-fucosyltransferase (FUT8) catalyzes the transfer of a fucosyl moiety from GDP-fucose to the innermost asparagine-linked N-acetylglucosamine residue of glycoproteins. In mammals, this glycosylation has an important function in many fundamental biological processes and although no essential role has been demonstrated yet in all animals, FUT8 amino acid (aa) sequence and FUT8 activity are very well conserved throughout the animal kingdom. We have cloned the cDNA and the complete gene encoding the FUT8 in the Sf9 (Spodoptera frugiperda) lepidopteran cell line. As in most animal genomes, fut8 is a single-copy gene organized in different exons. The open reading frame contains 12 exons, a characteristic that seems to be shared by all lepidopteran fut8 genes. We chose to study the gene structure as a way to characterize the evolutionary relationships of the fut8 genes in metazoans. Analysis of the intron-exon organization in 56 fut8 orthologs allowed us to propose a model for fut8 evolution in metazoans. The presence of a highly variable number of exons in metazoan fut8 genes suggests a complex evolutionary history with many intron gain and loss events, particularly in arthropods, but not in chordata. Moreover, despite the high conservation of lepidoptera FUT8 sequences also in vertebrates and hymenoptera, the exon-intron organization of hymenoptera fut8 genes is order-specific with no shared exons. This feature suggests that the observed intron losses and gains may be linked to evolutionary innovations, such as the appearance of new orders.

  8. Transgenerational epigenetic effects on innate immunity in broilers: an underestimated field to be explored? (United States)

    Berghof, T V L; Parmentier, H K; Lammers, A


    Transgenerational epigenetics is becoming more and more important for understanding the variation of physiological responses of individuals to the environment and the inheritance of these responses based on all mechanisms other than the actual DNA nucleotide sequence. Transgenerational epigenetics is the phenomenon that the information of the environment of (usually) a female animal is translated into memory-like responses preparing the offspring. As a consequence, individuals of the next generation may show different phenotypic traits depending whether their mothers were kept under different environmental conditions. This may result in either positive or negative effects on the next-generation individuals, which is different from individuals from mothers that have been kept in a different environment. Transgenerational epigenetic effects have been proposed and indicated for specific immune (T cell and antibody) responses (especially in mammals, but also in birds) and innate immunity (nonvertebrates), but surprisingly very little is known of transgenerational effects on innate immunity in chickens. Given the short lifespan of the chicken and therefore the likely dependence of chicken on innate immune mechanisms, more attention should be given to this arm of immunity and mechanisms of inheritance including transgenerational effects that can be initiated in the breeder generation. In addition, it is becoming evident that innate immunity also underlies metabolic disorders in broilers. In the current paper, we will argue that although very little is known of transgenerational effects of innate immunity in poultry, more attention should be given to this type of study. We will illustrate examples of transgenerational epigenetics, and finally propose strategies that should reveal the presence of transgenerational epigenetic effects on innate immunity in chickens and strategies to modulate breeder birds such that these effects positively affect innate immunity of broilers

  9. Osteoporosis and its association with non-gonadal hormones involved in hypertension, adiposity and hyperglycaemia. (United States)

    Poudyal, Hemant; Brown, Lindsay


    Osteoporosis is a high-prevalence disease, particularly in developed countries, and results in high costs both to the individual and to society through associated fragility fractures. There is an urgent need for identification of novel drug targets and development of new anti-osteoporotic agents. Between 30 and 80% of osteoporotic fractures cannot be prevented despite current treatments achieving relative fracture risk reduction of up to 20%, 50%, and 70% for non-vertebral, hip and spine fractures, respectively. Traditionally, the decline in gonadal hormones has been studied as the sole hormonal determinant for the loss of bone mineral density in osteoporosis. However, recent studies have identified receptors for numerous non-gonadal hormones such as PTH, angiotensin II, leptin, adiponectin, insulin and insulin-like growth factor-1 on the osteoblast lineage cells that directly regulate bone turnover. These hormones are also involved in the pathogenesis of metabolic syndrome risk factors, particularly hypertension, type-II diabetes and obesity. By activating their respective receptors on osteoblastic lineage cells, these hormones appear to act through a common mechanism by down-regulating receptors for activation of nuclear factor kappa B ligand (RANKL) and up-regulating osteoprotegerin (OPG) with inverse responses for adiponectin. Receptors for amylin, gastric inhibitory polypeptide and ghrelin and have also been identified on the osteoblast lineage cells although the roles of these receptors in bone turnover are controversial or poorly studied. Moreover, bone turnover may be independently regulated by modulation of osteoclast-osteoblast function and bone marrow adiposity. Leptin appears to be the only hormone that is a known regulator of both bone mineralisation and bone adiposity.

  10. When, where and how osteoporosis-associated fractures occur: an analysis from the Global Longitudinal Study of Osteoporosis in Women (GLOW.

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    Aline G Costa

    Full Text Available To examine when, where and how fractures occur in postmenopausal women.We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW, including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3.Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip. Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68-86% of NHNV and 68-83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling.In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year.

  11. SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice (United States)

    Börjesson, Anna E.; Farman, Helen H.; Movérare-Skrtic, Sofia; Engdahl, Cecilia; Antal, Maria Cristina; Koskela, Antti; Tuukkanen, Juha; Carlsten, Hans; Krust, Andrée; Chambon, Pierre; Sjögren, Klara; Lagerquist, Marie K.; Windahl, Sara H.


    The bone-sparing effect of estrogens is mediated primarily via estrogen receptor (ER)α, which stimulates gene transcription through activation function (AF)-1 and AF-2. The role of ERαAF-1 for the estradiol (E2) effects is tissue specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofoxifene (Las), and bazedoxifene (Bza) can be used to treat postmenopausal osteoporosis. They all reduce the risk for vertebral fractures, whereas Las and partly Bza, but not Ral, reduce the risk for nonvertebral fractures. Here, we have compared the tissue specificity of Ral, Las, and Bza and evaluated the role of ERαAF-1 for the effects of these SERMs, with an emphasis on bone parameters. We treated ovariectomized (OVX) wild-type (WT) mice and OVX mice lacking ERαAF-1 (ERαAF-10) with E2, Ral, Las, or Bza. All three SERMs increased trabecular bone mass in the axial skeleton. In the appendicular skeleton, only Las increased the trabecular bone volume/tissue volume and trabecular number, whereas both Ral and Las increased the cortical bone thickness and strength. However, Ral also increased cortical porosity. The three SERMs had only a minor effect on uterine weight. Notably, all evaluated effects of these SERMs were absent in ovx ERαAF-10 mice. In conclusion, all SERMs had similar effects on axial bone mass. However, the SERMs had slightly different effects on the appendicular skeleton since only Las increased the trabecular bone mass and only Ral increased the cortical porosity. Importantly, all SERM effects require a functional ERαAF-1 in female mice. These results could lead to development of more specific treatments for osteoporosis. PMID:27048997

  12. Pharmacological treatment of osteoporosis for people over 70. (United States)

    Moro Alvarez, M Jesús; Díaz-Curiel, Manuel


    Osteoporosis has been defined as "a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with consequent increase in bone fragility and susceptibility to fracture". The impact of osteoporosis is most pronounced in elderly populations who run the greatest risk of fractures. The probability of developing mainly hip, vertebral and other non-vertebral fractures (for example, a Colles fracture) not only depends on bone mineral density (BMD) but also on age. Older patients are more susceptible to fracture than younger patients with the same BMD T-score. As the older population increases, the incidence of osteoporotic fractures is expected to rise dramatically over the next few decades. Although hip fractures are considered to be the most severe and economically important osteoporotic fracture, vertebral fractures also lead to adverse health outcomes, including back pain, height loss and kyphosis. These changes may result in significant declines in physical performance, function and, ultimately, loss of independence. The challenge for physicians is to prevent bone loss, to diagnose and treat osteoporosis before fractures occur, and to treat patients who have already experienced a fracture to prevent recurrent fractures. The objective of this review is to analyze the capacity to reduce fractures as the key element to evaluate the effectiveness of available medications: calcium and Vitamin D, bone formation drugs, antiresortive drugs, and dual-effect drugs. In view of the paucity of information about treatment of osteoporosis in the elderly population, available studies were not designed with this objective, so that this article reviews data mostly deriving from post-hoc analysis or sub-analysis of the main phase III clinical trials of each of the tested medications.

  13. Rationale and Safety Assessment of a Novel Intravaginal Drug-Delivery System with Sustained DL-Lactic Acid Release, Intended for Long-Term Protection of the Vaginal Microbiome.

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    Hans Verstraelen

    Full Text Available Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9 mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this

  14. Autophagy contributes to regulation of nuclear dynamics during vegetative growth and hyphal fusion in Fusarium oxysporum. (United States)

    Corral-Ramos, Cristina; Roca, M Gabriela; Di Pietro, Antonio; Roncero, M Isabel G; Ruiz-Roldán, Carmen


    In the fungal pathogen Fusarium oxysporum, vegetative hyphal fusion triggers nuclear mitotic division in the invading hypha followed by migration of a nucleus into the receptor hypha and degradation of the resident nucleus. Here we examined the role of autophagy in fusion-induced nuclear degradation. A search of the F. oxysporum genome database for autophagy pathway components identified putative orthologs of 16 core autophagy-related (ATG) genes in yeast, including the ubiquitin-like protein Atg8, which is required for the formation of autophagosomal membranes. F. oxysporum Foatg8Δ mutants were generated in a strain harboring H1-cherry fluorescent protein (ChFP)-labeled nuclei to facilitate analysis of nuclear dynamics. The Foatg8Δ mutants did not show MDC-positive staining in contrast to the wild type and the FoATG8-complemented (cFoATG8) strain, suggesting that FoAtg8 is required for autophagy in F. oxysporum. The Foatg8Δ strains displayed reduced rates of hyphal growth, conidiation, and fusion, and were significantly attenuated in virulence on tomato plants and in the nonvertebrate animal host Galleria mellonella. In contrast to wild-type hyphae, which are almost exclusively composed of uninucleated hyphal compartments, the hyphae of the Foatg8Δ mutants contained a significant fraction of hyphal compartments with 2 or more nuclei. The increase in the number of nuclei per hyphal compartment was particularly evident after hyphal fusion events. Time-lapse microscopy analyses revealed abnormal mitotic patterns during vegetative growth in the Foatg8Δ mutants. Our results suggest that autophagy mediates nuclear degradation after hyphal fusion and has a general function in the control of nuclear distribution in F. oxysporum.

  15. Bazedoxifene: the evolving role of third-generation selective estrogen-receptor modulators in the management of postmenopausal osteoporosis. (United States)

    Komm, Barry S; Chines, Arkadi A


    Osteoporosis is a significant public health concern, particularly for postmenopausal women. Current treatment options may not be appropriate for all women. Selective estrogen-receptor modulators (SERMs) are a class of molecules with tissue-selective activity. Bazedoxifene is currently in clinical development for the prevention and treatment of postmenopausal osteoporosis. In a 2-year, phase III, osteoporosis prevention study (N = 1583), bazedoxifene 10, 20, and 40 mg was shown to preserve bone mineral density and decrease biochemical markers of bone turnover compared with placebo in postmenopausal women at risk for osteoporosis. In a pivotal 3-year, phase III, osteoporosis treatment study (N = 7492), bazedoxifene 20 and 40 mg significantly reduced the incidence of new vertebral fractures compared with placebo (p osteoporosis. In a post hoc subgroup analysis of women at higher risk for fracture (n = 1772), bazedoxifene 20 mg significantly reduced the risk of nonvertebral fractures versus placebo (p = 0.02) and raloxifene 60 mg (p = 0.05). Bazedoxifene 20 mg has demonstrated sustained efficacy in reducing the risk of vertebral fractures over 5 and 7 years. Overall, bazedoxifene was generally safe and well tolerated, with favorable endometrial and breast safety profiles. As with other SERMs, the rate of deep vein thrombosis was higher in the bazedoxifene groups compared with placebo at 3 and 5 years. Considering its demonstrated efficacy and safety, bazedoxifene may be an appropriate osteoporosis therapy for women who cannot take or are unwilling to take bisphosphonates because of safety or tolerability issues. Bazedoxifene may also be appropriate for younger women at increased fracture risk who are concerned about the effects of long-term bisphosphonate therapy. This article reviews the results of key clinical trials of bazedoxifene for the prevention and treatment of postmenopausal osteoporosis and describes its role in clinical

  16. Cysteine proteinases and cystatins

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    Adeliana S. Oliveira


    Full Text Available This review describeds the definition, localization, functions and examples of cysteine proteinases and their protein inhibitors in vertebrate, non-vertebrate animals and plants. These inhibitors are related with defense mechanisms of plant against pests. It also describes the factors involved in the specific cysteine proteinase-cystatin interaction and high degree of affinity and large specificity in this interaction which are not only represented by the compatibility between amino acid residues of the active site involved in catalysis, but also of all amino acid residues that participante in the enzyme-inhibitor interaction.Nesta revisão foram descritas definições, localizações, funções e exemplos de proteinases cisteínicas e suas proteinas inibidoras em animais vertebrados e invertebrados e plantas. Tratamos principalmente com aqueles inibidores que são relatados com o mecanismo de defesa da planta contra pestes. Em adição, comentamos sobre recentes trabalhos que contribuíram para uma melhor compreenção dos fatores envolvidos na interação específica proteinase cisteínica-cistatina. Por outro lado, chamamos atenção para o alto grau de afinidade e grande especificidade na interação que não são apenas representadas pela compatibilidade entre os residuos de aminoácidos do sítio ativo envolvidos na catalise, mas também de todos os resíduos de aminoácidos que participam da interação enzima-inibidor.

  17. Higher prevalence of morphometric vertebral fractures in patients with recent coronary events independently of BMD measurements. (United States)

    Silva, Henrique C; Pinheiro, Marcelo M; Genaro, Patrícia S; Castro, Charlles H M; Monteiro, Carlos M C; Fonseca, Francisco A H; Szejnfeld, Vera L


    Cardiovascular disease and osteoporosis are important causes of morbi-mortality in the elderly and may be mutually related. Low bone mineral density (BMD) may be associated with increased risk of cardiovascular events. We investigated the prevalence of low bone mass and fractures in metabolic syndrome patients with acute coronary events. A case-control study was conducted with 150 individuals (30-80years-old) with metabolic syndrome. Seventy-one patients had had an acute coronary syndrome episode in the last 6months (cases) and the remaining 79 had no coronary event (controls). Cases and controls were matched for gender, BMI and age. DXA measurements and body composition were performed while spine radiographs surveyed for vertebral fractures and vascular calcification. Biochemical bone and metabolic parameters were measured in all patients. No statistically significant difference in BMD and the prevalence of osteopenia, osteoporosis and non-vertebral fractures was observed between cases and controls. The prevalence of vertebral fractures and all fractures was higher in the cases (14.1 versus 1.3%, p=0.003 and 22.5versus7.6%, p=0.010, respectively). Male gender (OR=0.22 95% CI 0.58 to 0.83, p=0.026) and daily intake of more than 3 portions of dairy products (OR=0.19 95% CI 0.49 to 0.75, p=0.017) were associated with lower prevalence of fractures. Cases had higher risk for fractures (OR=4.97, 95% CI 1.17 to 30.30, p=0.031). Bone mass and body composition parameters were not associated with cardiovascular risk factors or bone mineral metabolism. Patients with fragility fractures had higher OPG serum levels than those without fractures (p<0.001). Our findings demonstrated that patients with recent coronary events have a higher prevalence of vertebral fractures independently of BMD.

  18. The Tromsø Study: physical activity and the incidence of fractures in a middle-aged population. (United States)

    Joakimsen, R M; Fønnebø, V; Magnus, J H; Størmer, J; Tollan, A; Søgaard, A J


    We have studied the relation of occupational and recreational physical activity to fractures at different locations. All men born between 1925 and 1959 and all women born between 1930 and 1959 in the city of Tromsø were invited to participate in surveys in 1979-1980 and 1986-1987 (The Tromsø Study). Of 16,676 invited persons, 12,270 (73.6%) attended both surveys. All nonvertebral fractures (n = 1435) sustained from 1988 to 1995 were registered in the only hospital in the area. Average age in the middle of the follow-up period (December 31, 1991) was 47.3 years among men and 4501 years among women, ranging from 32 to 66 years. Fracture incidence increased with age at all locations among women, but it decreased with or was independent of age among men. Low-energetic fractures constituted 74.4% of all fractures among women and 55.2% among men. When stratifying by fracture location, the most physically active persons among those 45 years or older suffered fewer fractures in the weight-bearing skeleton (relative risk [RR] 0.6, confidence interval [CI] 0.4-0.9, age-adjusted), but not in the non-weight-bearing skeleton (RR 1.0, CI 0.7-1.2, age-adjusted) compared with sedentary persons. The relative-risk of a low-energetic fracture in the weight-bearing skeleton among the most physically active middle-aged was 0.3 (CI 0.1-0.7) among men and 0.9 (CI 0.4-1.8) among women compared with the sedentary when adjusted for age, body mass index, body height, tobacco smoking, and alcohol and milk consumption. It seems that the beneficial effect on the skeleton of weight-bearing activity is reflected also in the incidence of fractures at different sites.

  19. Association of serum fibroblast growth factor 23 (FGF23) and incident fractures in older men: the Osteoporotic Fractures in Men (MrOS) study. (United States)

    Lane, Nancy E; Parimi, Neeta; Corr, Maripat; Yao, Wei; Cauley, Jane A; Nielson, Carrie M; Ix, Joseph H; Kado, Deborah; Orwoll, Eric


    Normal mineral metabolism is critical for skeletal integrity, and recently serum fibroblast growth factor 23 (FGF23) levels were found to be directly related to overall fracture risk in elderly Swedish men. To confirm this association, we performed a prospective case-cohort study to understand the relation of FGF23 and fracture risk in older white men enrolled in the Osteoporotic Fractures in Men (MrOS) study. In the cohort of 5994 men attending the baseline MrOS examination, we evaluated a subgroup of 387 men with incident nonvertebral fracture including 73 hip fractures and a sample of 1385 men randomly selected from the cohort with baseline mineral and calcium hormone measurements. FGF23 was measured in baseline serum samples by ELISA (Millipore, Billerica, MA, USA). Modified Cox proportional hazards models that account for case-cohort study design were used to estimate the relative hazards (RH) of fracture in men across quartiles of FGF23. Subjects were also stratified by renal function, and RH per strata was estimated in men with the highest quartile of FGF23 compared with quartiles 3, 2, and 1. Overall, there was no difference in risk of nonspine or hip fracture by baseline FGF23. However, associations differed by strata of eGFRCrCy . Among men with eGFRCrCys 60 mL/min/1.73 m2 (304/1370 fractures) the RH was 0.91 (95% CI 0.66-1.25) after adjustment for age, clinic site, body mass index, race, total hip bone mineral density, vitamin D, parathyroid hormone, alcohol use, physical activity, fracture history, and serum phosphorus. Serum FGF23 levels are not associated with incident fractures in elderly men overall. However, higher levels of serum FGF23 are associated with fracture risk in those with poor renal function.

  20. Long-term treatment with bisphosphonates and their safety in postmenopausal osteoporosis

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    Michael Pazianas


    Full Text Available Michael Pazianas1, Cyrus Cooper1,2, F Hal Ebetino3, R Graham G Russell1,41The Botnar Research Centre and Oxford University Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Diseases, Nuffield Orthopaedic Centre, Headington, Oxford, UK; 2MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, UK; 3Warner Chilcott, New Jersey, USA; 4The Mellanby Centre for Bone Research, Department of Human Metabolism, Sheffield University Medical School, Sheffield, UKAbstract: Bisphosphonates are the leading drugs for the treatment of osteoporosis. In ­randomized controlled trials (RCTs, alendronate, risedronate, and zoledronate have shown to reduce the risk of vertebral, nonvertebral, and hip fractures, whereas RCTs with ibandronate show antifracture efficacy at vertebral sites. Bisphosphonates are generally well tolerated and safe. Nevertheless, adverse events have been noted, and it is important to consider the strength of the evidence for causal relationships. Effects on the gastrointestinal tract and kidney function are well recognized, as are transient acute-phase reactions. Atrial fibrillation was first identified as a potential adverse event in a zoledronate trial, but subsequent trials and analyses failed to substantiate an association with bisphosphonates. Case reports have suggested a relationship between oral bisphosphonates and esophageal cancer, but this has not been demonstrated in epidemiologic studies. A possible association between bisphosphonate use and osteonecrosis of the jaw (ONJ has also been suggested. However, the risk of ONJ in patients with osteoporosis appears to be very low, with no evidence from prospective RCTs of a causal association. There are reports of occasional occurrence of subtrochanteric or diaphyseal fractures in osteoporotic patients, but an association with bisphosphonate therapy is not substantiated by

  1. Clinical utility of risedronate in postmenopausal osteoporosis: patient considerations with delayed-release formulation

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    Boyanov M


    Full Text Available Plamen Kinov1, Mihail Boyanov21Department of Orthopedics and Traumatology, University Hospital Queen Giovanna – ISUL, 2Department of Internal Medicine, Clinic of Endocrinology, University Hospital Alexandrovska, Medical University of Sofia, Sofia, BulgariaAbstract: Bisphosphonates are the most widely prescribed treatment for postmenopausal osteoporosis, secondary osteoporosis, and male osteoporosis. Notwithstanding their high effectiveness and favorable safety profile, the adherence to bisphosphonate treatment remains low. Different treatment strategies aim to improve the clinical effectiveness of bisphosphonate therapy. This review paper assesses the clinical utility of oral intermittent risedronate in the treatment of postmenopausal osteoporosis. The new delayed-release risedronate formulation is a safer and easy to use alternative to other risedronate therapy. Oral risedronate, a potent nitrogen-containing bisphosphonate, has been extensively studied using daily regimens. A new intermittent (weekly dosing regimen confirmed its clinical effectiveness in relation to vertebral and nonvertebral fracture prevention. The absence of significant differences in the incidence of adverse effects confirmed the favorable tolerability of the weekly dosage. In efforts to improve patient adherence to treatment, an innovative, delayed-release formulation of risedronate, which ensures adequate bioavailability of the active compound when taken with food, was introduced. The once-weekly delayed-release formulation of risedronate proved to be noninferior to the daily dosage of risedronate in terms of bone mineral density and markers of bone turnover. In addition, the incidence of new morphometric vertebral fractures was comparable in both treatment regimens. The new delayed-release formulation of risedronate showed a favorable safety profile. Delayed-release risedronate is a promising, new, effective, and convenient alternative to current bisphosphonate

  2. Update on denosumab in the management of postmenopausal osteoporosis: patient preference and adherence

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    Cairoli E


    Full Text Available Elisa Cairoli,1,2 Cristina Eller-Vainicher,1 Iacopo Chiodini1,2 1Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, Padiglione Granelli, Milan, Italy; 2Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy Abstract: Patient adherence to many osteoporosis treatments, primarily bisphosphonates, is generally poor, thus leading to a significant reduction in antifracture efficacy. Patient perceptions about the necessity of the prescribed medication to treat osteoporosis and the concerns about the potential adverse effects are important and potentially modifiable determinants of adherence, in addition to other factors, such as difficult dosing regimens and high dosing frequency. Denosumab (Dmab is a fully human monoclonal antibody against the receptor activator of nuclear factor-κB ligand (RANKL, which, through the prevention of the RANKL/RANK interaction, inhibits osteoclast-mediated bone resorption and significantly reduces the risk of vertebral, nonvertebral, and hip fractures. It is administered subcutaneously every 6 months for the treatment of postmenopausal osteoporosis. Preference and adherence to Dmab treatment were assessed in various clinical trials. Although with some limitations, available data suggest that Dmab is preferred to bisphosphonates, produces greater satisfaction than bisphosphonates, and would be preferentially chosen for long-term treatment. Moreover, patient perceptions about the necessity of Dmab treatment clearly outweigh the concerns about the injections, and positive beliefs about treatment positively influence medication-taking behavior. According to these data, Dmab may represent a reasonable alternative to bisphosphonates, particularly for osteoporotic women in whom a suboptimal or even poor adherence to oral treatments is expected. Keywords: denosumab, RANKL, osteoporosis treatment, preference, satisfaction, adherence

  3. Determinants of Transitional Zone Area and Porosity of the Proximal Femur Quantified In Vivo in Postmenopausal Women. (United States)

    Shigdel, Rajesh; Osima, Marit; Lukic, Marko; Ahmed, Luai A; Joakimsen, Ragnar M; Eriksen, Erik F; Bjørnerem, Åshild


    Bone architecture as well as size and shape is important for bone strength and risk of fracture. Most bone loss is cortical and occurs by trabecularization of the inner part of the cortex. We therefore wanted to identify determinants of the bone architecture, especially the area and porosity of the transitional zone, an inner cortical region with a large surface/matrix volume available for intracortical remodeling. In 211 postmenopausal women aged 54 to 94 years with nonvertebral fractures and 232 controls from the Tromsø Study, Norway, we quantified femoral subtrochanteric architecture in CT images using StrAx1.0 software, and serum levels of bone turnover markers (BTM, procollagen type I N-terminal propeptide and C-terminal cross-linking telopeptide of type I collagen). Multivariable linear and logistic regression analyses were used to quantify associations of age, weight, height, and bone size with bone architecture and BTM, and odds ratio (OR) for fracture. Increasing age, height, and larger total cross-sectional area (TCSA) were associated with larger transitional zone CSA and transitional zone CSA/TCSA (standardized coefficients [STB] = 0.11 to 0.80, p ≤ 0.05). Increasing weight was associated with larger TCSA, but smaller transitional zone CSA/TCSA and thicker cortices (STB = 0.15 to 0.22, p 51 (95% CI, 1.23 to 1.85), respectively. Cortical bone architecture is determined mainly by bone size as built during growth and is modified by lifestyle factors throughout life through bone turnover. Fracture cases exhibited larger transitional zone area and porosity, highlighting the importance of cortical bone architecture for fracture propensity.

  4. A Hox regulatory network of hindbrain segmentation is conserved to the base of vertebrates. (United States)

    Parker, Hugo J; Bronner, Marianne E; Krumlauf, Robb


    A defining feature governing head patterning of jawed vertebrates is a highly conserved gene regulatory network that integrates hindbrain segmentation with segmentally restricted domains of Hox gene expression. Although non-vertebrate chordates display nested domains of axial Hox expression, they lack hindbrain segmentation. The sea lamprey, a jawless fish, can provide unique insights into vertebrate origins owing to its phylogenetic position at the base of the vertebrate tree. It has been suggested that lamprey may represent an intermediate state where nested Hox expression has not been coupled to the process of hindbrain segmentation. However, little is known about the regulatory network underlying Hox expression in lamprey or its relationship to hindbrain segmentation. Here, using a novel tool that allows cross-species comparisons of regulatory elements between jawed and jawless vertebrates, we report deep conservation of both upstream regulators and segmental activity of enhancer elements across these distant species. Regulatory regions from diverse gnathostomes drive segmental reporter expression in the lamprey hindbrain and require the same transcriptional inputs (for example, Kreisler (also known as Mafba), Krox20 (also known as Egr2a)) in both lamprey and zebrafish. We find that lamprey hox genes display dynamic segmentally restricted domains of expression; we also isolated a conserved exonic hox2 enhancer from lamprey that drives segmental expression in rhombomeres 2 and 4. Our results show that coupling of Hox gene expression to segmentation of the hindbrain is an ancient trait with origin at the base of vertebrates that probably led to the formation of rhombomeric compartments with an underlying Hox code.

  5. Origins, Innovations, and Diversification of Suction Feeding in Vertebrates. (United States)

    Wainwright, Peter C; McGee, Matthew D; Longo, Sarah J; Hernandez, L Patricia


    We review the origins, prominent innovations, and major patterns of diversification in suction feeding by vertebrates. Non-vertebrate chordates and larval lamprey suspension-feed by capturing small particles in pharyngeal mucous. In most of these lineages the gentle flows that transport particles are generated by buccal cilia, although larval lamprey and thaliacean urochordates have independently evolved a weak buccal pump to generate an oscillating flow of water that is powered by elastic recovery of the pharynx following compression by buccal muscles. The evolution of jaws and the hyoid facilitated powerful buccal expansion and high-performance suction feeding as found today throughout aquatic vertebrates. We highlight three major innovations in suction feeding. Most vertebrate suction feeders have mechanisms that occlude the corners of the open mouth during feeding. This produces a planar opening that is often nearly circular in shape. Both features contribute to efficient flow of water into the mouth and help direct the flow to the area directly in front of the mouth's aperture. Among several functions that have been identified for protrusion of the upper jaw, is an increase in the hydrodynamic forces that suction feeders exert on their prey. Protrusion of the upper jaw has evolved five times in ray-finned fishes, including in two of the most successful teleost radiations, cypriniforms and acanthomorphs, and is found in about 60% of living teleost species. Diversification of the mechanisms of suction feeding and of feeding behavior reveals that suction feeders with high capacity for suction rarely approach their prey rapidly, while slender-bodied predators with low capacity for suction show the full range of attack speeds. We hypothesize that a dominant axis of diversification among suction feeders involves a trade-off between the forces that are exerted on prey and the volume of water that is ingested.

  6. A Biodiversity Informatics Approach to Ethnobotany: Meta-analysis of Plant Use Patterns in Ecuador

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    Lucia de la Torre


    Full Text Available We explored the relative importance of ecosystem diversity, socioeconomic, environmental, and geographical factors in determining the pattern and diversity of people's plant use in Ecuador, based on existing ethnobotanic investigations and a large database of georeferenced plant collections. For each of 40 communities, we determined the number of plants used and their distribution among 12 use categories. Plant species richness of the ecosystem surrounding each village was determined using herbarium data and rarefaction. Variation in socioeconomic, environmental, and geographical indicator variables at the community level was summarized using Principal Component Analysis (PCA. Data were then analyzed using multiple regression and ordination analysis. We found a significant positive relationship between the number of plant species used and ecosystem species richness, whereas socioconomic, environmental, and geographical factors had no significance. However, ordination analysis did show a clear link among these factors and plant use patterns, i.e., the relative importance of different use categories. Study communities were divided into two groups: 1 Andean and coastal communities with better access to public services and markets categorized by high scores in these use classes: medicinal, social, food additives, environmental, apicolous (of economic interest in apiculture, and toxic to nonvertebrates; and 2 Amazonian remote communities with high scores for these use classes: food, fuel, materials, vertebrate and invertebrate food, and toxic to vertebrates. Our findings suggest that economic and social development affects plant use patterns in a selective way. Some traditional uses will persist despite increased infrastructure development and habitat disturbance, whereas others that reflect subsistence strategies dependent on conserved natural habitats may soon disappear. The study incorporates more than 20 years of ethnobotanical research effort

  7. Investigating the Role of the Host Multidrug Resistance Associated Protein Transporter Family in Burkholderia cepacia Complex Pathogenicity Using a Caenorhabditis elegans Infection Model (United States)

    Tedesco, Pietro; Visone, Marco; Parrilli, Ermenegilda; Tutino, Maria Luisa; Perrin, Elena; Maida, Isabel; Fani, Renato; Ballestriero, Francesco; Santos, Radleigh; Pinilla, Clemencia; Di Schiavi, Elia; Tegos, George; de Pascale, Donatella


    This study investigated the relationship between host efflux system of the non-vertebrate nematode Caenorhabditis elegans and Burkholderia cepacia complex (Bcc) strain virulence. This is the first comprehensive effort to profile host-transporters within the context of Bcc infection. With this aim, two different toxicity tests were performed: a slow killing assay that monitors mortality of the host by intestinal colonization and a fast killing assay that assesses production of toxins. A Virulence Ranking scheme was defined, that expressed the toxicity of the Bcc panel members, based on the percentage of surviving worms. According to this ranking the 18 Bcc strains were divided in 4 distinct groups. Only the Cystic Fibrosis isolated strains possessed profound nematode killing ability to accumulate in worms’ intestines. For the transporter analysis a complete set of isogenic nematode single Multidrug Resistance associated Protein (MRP) efflux mutants and a number of efflux inhibitors were interrogated in the host toxicity assays. The Bcc pathogenicity profile of the 7 isogenic C. elegans MRP knock-out strains functionality was classified in two distinct groups. Disabling host transporters enhanced nematode mortality more than 50% in 5 out of 7 mutants when compared to wild type. In particular mrp-2 was the most susceptible phenotype with increased mortality for 13 out 18 Bcc strains, whereas mrp-3 and mrp-4 knock-outs had lower mortality rates, suggesting a different role in toxin-substrate recognition. The use of MRP efflux inhibitors in the assays resulted in substantially increased (>40% on average) mortality of wild-type worms. PMID:26587842

  8. From cyst to tubule: innovations in vertebrate spermatogenesis. (United States)

    Yoshida, Shosei


    Although vertebrates share many common traits, their germline development and function exhibit significant divergence. In particular, this article focuses on their spermatogenesis. The fundamental elements that constitute vertebrate spermatogenesis and the evolutionary changes that occurred upon transition from water to land will be discussed. The life-long continuity of spermatogenesis is supported by the function of stem cells. Series of mitotic and meiotic germ cell divisions are 'incomplete' due to incomplete cytokinesis, forming syncytia interconnected via intercellular bridges (ICBs). Throughout this process, germ cells are supported by appropriate microenvironments established primarily by somatic Sertoli cells. In anamniotes (fish and amphibians) spermatogenesis progresses in cysts, in which developing germ cell syncytia are individually encapsulated by Sertoli cells. Accordingly, Sertoli cells undergo turnover with germ cells that they nourish. This mode of cystic spermatogenesis is also observed in nonvertebrates as insects. In amniotes (reptiles, birds, and mammals), however, Sertoli cells do not turn over but comprise a persistent structure of seminiferous tubules. Sertoli cells nourish different stages of germ cells simultaneously in distinct regions of their surface. This function of Sertoli cells is spatiotemporally orchestrated, and the seminiferous epithelial cycle and spermatogenic wave make the seminiferous tubules a high-throughput factory for sperm production. Furthermore, contrary to the organized differentiating cells, undifferentiated spermatogonia that comprise the stem cell compartment exhibit active motion over the basal layer of seminiferous tubules and the frequent breakdown of ICBs. Thus, amniote seminiferous tubules represent a typical facultative (or open) niche environment without a stem cell tethering anatomically defined niche. WIREs Dev Biol 2016, 5:119-131. doi: 10.1002/wdev.204 For further resources related to this article

  9. Molecular Evolution and Functional Divergence of Trace Amine-Associated Receptors.

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    Seong-Il Eyun

    Full Text Available Trace amine-associated receptors (TAARs are a member of the G-protein-coupled receptor superfamily and are known to be expressed in olfactory sensory neurons. A limited number of molecular evolutionary studies have been done for TAARs so far. To elucidate how lineage-specific evolution contributed to their functional divergence, we examined 30 metazoan genomes. In total, 493 TAAR gene candidates (including 84 pseudogenes were identified from 26 vertebrate genomes. TAARs were not identified from non-vertebrate genomes. An ancestral-type TAAR-like gene appeared to have emerged in lamprey. We found four therian-specific TAAR subfamilies (one eutherian-specific and three metatherian-specific in addition to previously known nine subfamilies. Many species-specific TAAR gene duplications and losses contributed to a large variation of TAAR gene numbers among mammals, ranging from 0 in dolphin to 26 in flying fox. TAARs are classified into two groups based on binding preferences for primary or tertiary amines as well as their sequence similarities. Primary amine-detecting TAARs (TAAR1-4 have emerged earlier, generally have single-copy orthologs (very few duplication or loss, and have evolved under strong functional constraints. In contrast, tertiary amine-detecting TAARs (TAAR5-9 have emerged more recently and the majority of them experienced higher rates of gene duplications. Protein members that belong to the tertiary amine-detecting TAAR group also showed the patterns of positive selection especially in the area surrounding the ligand-binding pocket, which could have affected ligand-binding activities and specificities. Expansions of the tertiary amine-detecting TAAR gene family may have played important roles in terrestrial adaptations of therian mammals. Molecular evolution of the TAAR gene family appears to be governed by a complex, species-specific, interplay between environmental and evolutionary factors.

  10. Childhood osteomyelitis-incidence and differentiation from other acute onset musculoskeletal features in a population-based study

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    Reiseter Tor


    Full Text Available Abstract Background Osteomyelitis can be difficult to diagnose and there has previously not been a prospective approach to identify all children in a defined geographic area. The aim of this study was to assess the annual incidence of osteomyelitis in children, describe the patient and disease characteristics in those with acute ( Methods In a population-based Norwegian study physicians were asked to refer all children with suspected osteomyelitis. Children with osteomyelitis received follow-up at six weeks, six months and thereafter as long as clinically needed. Results The total annual incidence rate of osteomyelitis was 13 per 100 000 (acute osteomyelitis 8 and subacute osteomyelitis 5 per 100 000. The incidence was higher in patients under the age of 3 than in older children (OR 2.9, 95%: CI 2.3–3.7. The incidence of non-vertebral osteomyelitis was higher than the incidence of vertebral osteomyelitis (10 vs. 3 per 100 000; p = .002. Vertebral osteomyelitis was more frequent in girls than in boys (OR 7.0, 95%: CI 3.3–14.7. ESR ≥ 40 mm/hr had the highest positive predictive laboratory value to identify osteomyelitis patients at 26% and MRI had a positive predictive value of 85%. Long-bone infection was found in 16 (43% patients. ESR, CRP, white blood cell count, neutrophils and platelet count were higher for patients with acute osteomyelitis than for patients with subacute osteomyelitis. Subacute findings on MRI and doctor's delay were more common in subacute osteomyelitis than in acute osteomyelitis patients. Blood culture was positive in 26% of the acute osteomyelitis patients and was negative in all the subacute osteomyelitis patients. Conclusion The annual incidence of osteomyelitis in Norway remains high. ESR values and MRI scan may help to identify osteomyelitis patients and differentiate acute and subacute osteomyelitis.

  11. Critical appraisal of denosumab in the treatment and prevention of postmenopausal osteoporosis and bone loss in patients undergoing hormone ablation

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    David L Kendler


    Full Text Available David L Kendler1, Kenneth Shawn Davison21Prohealth Clinical Research, University of British Columbia, Vancouver, British Columbia, Canada; 2Department of Medicine, Division of Immunology and Rheumatology, Laval University, Quebec, CanadaAbstract: Antiresorptive therapies are the mainstay for treating patients with excessively high rates of bone resorption. The receptor activator of nuclear factor-κB (RANK ligand (RANKL, secreted by osteoblasts, binds to the RANK receptor on the surface of preosteoclasts and osteoclasts to elicit osteoclast formation, survival, and activity. Osteoprotegerin, also secreted by the osteoblast, acts as a decoy RANK receptor reducing RANKL binding to RANK and reducing bone resorption. Denosumab, a fully human monoclonal antibody, has a high affinity and specificity for RANKL. Denosumab rapidly decreases bone resorption and increases bone mineral density (BMD at the lumbar spine, total hip, femoral neck, and one-third radius sites. In head-to-head trials, denosumab increased BMD and decreased bone resorption to a significantly greater degree than alendronate. In postmenopausal osteoporotic women, denosumab decreased the risk of vertebral fracture (68%, nonvertebral fracture (20%, and hip fracture (40% over 36 months, compared to placebo. In patients with iatrogenic hypogonadism, denosumab rapidly decreased markers of bone resorption and increased BMD. In men treated with GnRH agonist for prostate cancer, treatment with denosumab led to a 62% decreased risk of new vertebral fracture over 3 years, as compared to placebo. In all trials completed to date, comparable adverse events have been observed in both denosumab and placebo or treatment groups.Keywords: medication adherence, fracture, bone mineral density, bone turnover markers

  12. Ancestral state reconstruction by comparative analysis of a GRN kernel operating in echinoderms. (United States)

    Erkenbrack, Eric M; Ako-Asare, Kayla; Miller, Emily; Tekelenburg, Saira; Thompson, Jeffrey R; Romano, Laura


    Diverse sampling of organisms across the five major classes in the phylum Echinodermata is beginning to reveal much about the structure and function of gene regulatory networks (GRNs) in development and evolution. Sea urchins are the most studied clade within this phylum, and recent work suggests there has been dramatic rewiring at the top of the skeletogenic GRN along the lineage leading to extant members of the euechinoid sea urchins. Such rewiring likely accounts for some of the observed developmental differences between the two major subclasses of sea urchins-cidaroids and euechinoids. To address effects of topmost rewiring on downstream GRN events, we cloned four downstream regulatory genes within the skeletogenic GRN and surveyed their spatiotemporal expression patterns in the cidaroid Eucidaris tribuloides. We performed phylogenetic analyses with homologs from other non-vertebrate deuterostomes and characterized their spatiotemporal expression by quantitative polymerase chain reaction (qPCR) and whole-mount in situ hybridization (WMISH). Our data suggest the erg-hex-tgif subcircuit, a putative GRN kernel, exhibits a mesoderm-specific expression pattern early in Eucidaris development that is directly downstream of the initial mesodermal GRN circuitry. Comparative analysis of the expression of this subcircuit in four echinoderm taxa allowed robust ancestral state reconstruction, supporting hypotheses that its ancestral function was to stabilize the mesodermal regulatory state and that it has been co-opted and deployed as a unit in mesodermal subdomains in distantly diverged echinoderms. Importantly, our study supports the notion that GRN kernels exhibit structural and functional modularity, locking down and stabilizing clade-specific, embryonic regulatory states.

  13. Lactobacillus paracasei modulates the immune system of Galleria mellonella and protects against Candida albicans infection (United States)

    Rossoni, Rodnei Dennis; Fuchs, Beth Burgwyn; de Barros, Patrícia Pimentel; Velloso, Marisol dos Santos; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos; Mylonakis, Eleftherios


    Probiotics have been described as a potential strategy to control opportunistic infections due to their ability to stimulate the immune system. Using the non-vertebrate model host Galleria mellonella, we evaluated whether clinical isolates of Lactobacillus spp. are able to provide protection against Candida albicans infection. Among different strains of Lactobacillus paracasei, Lactobacillus rhamnosus and Lactobacillus fermentum, we verified that L. paracasei 28.4 strain had the greatest ability to prolong the survival of larvae infected with a lethal dose of C. albicans. We found that the injection of 107 cells/larvae of L. paracasei into G. mellonella larvae infected by C. albicans increased the survival of these insects compared to the control group (P = 0.0001). After that, we investigated the immune mechanisms involved in the protection against C. albicans infection, evaluating the number of hemocytes and the gene expression of antifungal peptides. We found that L. paracasei increased the hemocyte quantity (2.38 x 106 cells/mL) in relation to the control group (1.29 x 106 cells/mL), indicating that this strain is capable of raising the number of circulating hemocytes into the G. mellonella hemolymph. Further, we found that L. paracasei 28.4 upregulated genes that encode the antifungal peptides galiomicin and gallerymicin. In relation to the control group, L. paracasei 28.4 increased gene expression of galiomicin by 6.67-fold and 17.29-fold for gallerymicin. Finally, we verified that the prophylactic provision of probiotic led to a significant reduction of the number of fungal cells in G. mellonella hemolymph. In conclusion, L. paracasei 28.4 can modulate the immune system of G. mellonella and protect against candidiasis. PMID:28267809

  14. Hox cluster organization in the jawless vertebrate Petromyzon marinus. (United States)

    Force, Allan; Amores, Angel; Postlethwait, John H


    Large-scale gene amplifications may have facilitated the evolution of morphological innovations that accompanied the origin of vertebrates. This hypothesis predicts that the genomes of extant jawless fish, scions of deeply branching vertebrate lineages, should bear a record of these events. Previous work suggests that nonvertebrate chordates have a single Hox cluster, but that gnathostome vertebrates have four or more Hox clusters. Did the duplication events that produced multiple vertebrate Hox clusters occur before or after the divergence of agnathan and gnathostome lineages? Can investigation of lamprey Hox clusters illuminate the origins of the four gnathostome Hox clusters? To approach these questions, we cloned and sequenced 13 Hox cluster genes from cDNA and genomic libraries in the lamprey, Petromyzon marinus. The results suggest that the lamprey has at least four Hox clusters and support the model that gnathostome Hox clusters arose by a two-round-no-cluster-loss mechanism, with tree topology [(AB)(CD)]. A three-round model, however, is not rigorously excluded by the data and, for this model, the tree topologies [(D(C(AB))] and [(C(D(AB))] are most parsimonious. Gene phylogenies suggest that at least one Hox cluster duplication occurred in the lamprey lineage after it diverged from the gnathostome lineage. The results argue against two or more rounds of duplication before the divergence of agnathan and gnathostome vertebrates. If Hox clusters were duplicated in whole-genome duplication events, then these data suggest that, at most, one whole genome duplication occurred before the evolution of vertebrate developmental innovations.

  15. Evolution of developmental regulation in the vertebrate FgfD subfamily. (United States)

    Jovelin, Richard; Yan, Yi-Lin; He, Xinjun; Catchen, Julian; Amores, Angel; Canestro, Cristian; Yokoi, Hayato; Postlethwait, John H


    Fibroblast growth factors (Fgfs) encode small signaling proteins that help regulate embryo patterning. Fgfs fall into seven families, including FgfD. Nonvertebrate chordates have a single FgfD gene; mammals have three (Fgf8, Fgf17, and Fgf18); and teleosts have six (fgf8a, fgf8b, fgf17, fgf18a, fgf18b, and fgf24). What are the evolutionary processes that led to the structural duplication and functional diversification of FgfD genes during vertebrate phylogeny? To study this question, we investigated conserved syntenies, patterns of gene expression, and the distribution of conserved noncoding elements (CNEs) in FgfD genes of stickleback and zebrafish, and compared them with data from cephalochordates, urochordates, and mammals. Genomic analysis suggests that Fgf8, Fgf17, Fgf18, and Fgf24 arose in two rounds of whole genome duplication at the base of the vertebrate radiation; that fgf8 and fgf18 duplications occurred at the base of the teleost radiation; and that Fgf24 is an ohnolog that was lost in the mammalian lineage. Expression analysis suggests that ancestral subfunctions partitioned between gene duplicates and points to the evolution of novel expression domains. Analysis of CNEs, at least some of which are candidate regulatory elements, suggests that ancestral CNEs partitioned between gene duplicates. These results help explain the evolutionary pathways by which the developmentally important family of FgfD molecules arose and the deduced principles that guided FgfD evolution are likely applicable to the evolution of developmental regulation in many vertebrate multigene families.

  16. High prevalence of low bone mineral density in patients within 10 years of onset of ankylosing spondylitis: a systematic review. (United States)

    van der Weijden, M A C; Claushuis, T A M; Nazari, T; Lems, W F; Dijkmans, B A C; van der Horst-Bruinsma, I E


    Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease. Decreased bone mineral density (BMD) is a common complication of AS, with a prevalence range of 19 to 62 %. Many studies have shown decreased BMD in AS with long disease duration, but only a few studies investigated BMD in early AS. The prevalence of decreased BMD in early disease stages of AS has not yet been clearly described, and for that reason, we reviewed the literature which describes the prevalence of decreased BMD in AS patients with a short disease duration (articles which used the modified New York criteria for the diagnosis of AS, included patients with a disease duration of less than 10 years, and used the WHO criteria for osteopenia and osteoporosis. Decreased BMD was defined as a T score articles that acquired BMD data of lumbar spine and femoral neck by DXA were used. The literature search provided us 35 articles of which 7 matched all our criteria, and they will be further outlined in this review. The overall prevalence of decreased BMD of the articles reviewed is 54 % (n = 229/424) for lumbar spine and 51 % (n = 224/443) for femoral neck. The prevalence of osteopenia vs. osteoporosis for lumbar spine is 39 vs. 16 % and for femoral neck, 38 vs. 13 %. This review showed a high total prevalence of 51-54 % decreased BMD and 13-16 % osteoporosis in AS with a short disease duration. This high prevalence was not to be expected in a relatively young and predominantly male population. Further research is needed to determine the clinical relevance of this low BMD by investigating the relation between low BMD and vertebral and nonvertebral fractures at this early stage in AS.

  17. Incorporating bazedoxifene into the treatment paradigm for postmenopausal osteoporosis in Japan. (United States)

    Ohta, H; Solanki, J


    The incidence of osteoporosis-related fractures in Asian countries is steadily increasing. Optimizing osteoporosis treatment is especially important in Japan, where the rate of aging is increasing rapidlyelderly population is increasing rapidly and life expectancy is among the longest in the world. There are several therapies currently available in Japan for the treatment of postmenopausal osteoporosis, each with a unique risk/benefit profile. A novel selective estrogen receptor modulator, bazedoxifene (BZA), was recently approved for the treatment of postmenopausal osteoporosis in Japan. Results from a 2-year, phase 2 trial in postmenopausal Japanese women showed that BZA significantly improved lumbar spine and total hip bone mineral density compared with placebo, while maintaining endometrial and breast safety, consistent with results from 2 global, phase 3 trials including a 2-year osteoporosis prevention study and a 3-year osteoporosis treatment study. In the pivotal 3-year treatment study, BZA significantly reduced the incidence of new vertebral fractures compared with placebo; in a post hoc analysis of a subgroup of women at higher risk of fractures, BZA significantly reduced the risk of nonvertebral fractures compared with placebo and raloxifene. A 2-year extension of the 3-year treatment study demonstrated the sustained efficacy of BZA over 5 years of treatment. BZA was generally safe and well tolerated in these studies. In a "super-aging" society such as Japan, long-term treatment for postmenopausal osteoporosis is a considerable need. BZA may be considered as a first choice for younger women anticipating long-term treatment, and also an appropriate option for older women who are unable or unwilling to take bisphosphonates.

  18. Fauna and predator-prey relationships of Ettling, an actinopterygian fish-dominated Konservat-Lagerstatte from the Late Jurassic of southern Germany.

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    Martin Ebert

    Full Text Available The newly recognized Konservat-Lagerstätte of Ettling (Bavaria, field site of the Jura-Museum Eichstätt (JME, is unique among Late Jurassic plattenkalk basins (Solnhofen region in its abundant, extremely well preserved fossil vertebrates, almost exclusively fishes. We report actinopterygians (ginglymodins, pycnodontiforms, halecomorphs, aspidorynchiforms, "pholidophoriforms," teleosts; turtles; and non-vertebrates (echinoderms, arthropods, brachiopods, mollusks, jellyfish, sponges, biomats, plants in a current faunal list. Ettling has yielded several new fish species (Bavarichthys incognitus; Orthogonikleithrus hoelli; Aspidorhynchus sanzenbacheri; Macrosemimimus fegerti. Upper and lower Ettling strata differ in faunal content, with the lower dominated by the small teleost Orthogonikleithrus hoelli (absent from the upper layers, where other prey fishes, Leptolepides sp. and Tharsis sp., occur instead. Pharyngeal and stomach contents of Ettling fishes provide direct evidence that Orthogonikleithrus hoelli was a primary food source during early Ettling times. Scarcity of ammonites and absence of vampyromorph coleoids at Ettling differ markedly from the situation at other nearby localities in the region (e.g., Eichstätt, Painten, Schamhaupten, the Mörnsheim beds, where they are more common. Although the exact biochronological age of Ettling remains uncertain (lack of suitable index fossils, many Ettling fishes occur in other plattenkalk basins of Germany (e.g., Kelheim and France (Cerin dated as Late Kimmeridgian to Early Tithonian (eigeltingense horizon, suggesting a comparable geologic age. The Ettling deposits represent an independent basin within the larger Upper Jurassic "Solnhofen Archipelago", a shallow subtropical sea containing scattered islands, sponge-microbial and coral reefs, sandbars, and deeper basins on a vast carbonate platform along the northern margin of the Tethys Ocean.

  19. Fauna and predator-prey relationships of Ettling, an actinopterygian fish-dominated Konservat-Lagerstätte from the Late Jurassic of southern Germany. (United States)

    Ebert, Martin; Kölbl-Ebert, Martina; Lane, Jennifer A


    The newly recognized Konservat-Lagerstätte of Ettling (Bavaria), field site of the Jura-Museum Eichstätt (JME), is unique among Late Jurassic plattenkalk basins (Solnhofen region) in its abundant, extremely well preserved fossil vertebrates, almost exclusively fishes. We report actinopterygians (ginglymodins, pycnodontiforms, halecomorphs, aspidorynchiforms, "pholidophoriforms," teleosts); turtles; and non-vertebrates (echinoderms, arthropods, brachiopods, mollusks, jellyfish, sponges, biomats, plants) in a current faunal list. Ettling has yielded several new fish species (Bavarichthys incognitus; Orthogonikleithrus hoelli; Aspidorhynchus sanzenbacheri; Macrosemimimus fegerti). Upper and lower Ettling strata differ in faunal content, with the lower dominated by the small teleost Orthogonikleithrus hoelli (absent from the upper layers, where other prey fishes, Leptolepides sp. and Tharsis sp., occur instead). Pharyngeal and stomach contents of Ettling fishes provide direct evidence that Orthogonikleithrus hoelli was a primary food source during early Ettling times. Scarcity of ammonites and absence of vampyromorph coleoids at Ettling differ markedly from the situation at other nearby localities in the region (e.g., Eichstätt, Painten, Schamhaupten, the Mörnsheim beds), where they are more common. Although the exact biochronological age of Ettling remains uncertain (lack of suitable index fossils), many Ettling fishes occur in other plattenkalk basins of Germany (e.g., Kelheim) and France (Cerin) dated as Late Kimmeridgian to Early Tithonian (eigeltingense horizon), suggesting a comparable geologic age. The Ettling deposits represent an independent basin within the larger Upper Jurassic "Solnhofen Archipelago", a shallow subtropical sea containing scattered islands, sponge-microbial and coral reefs, sandbars, and deeper basins on a vast carbonate platform along the northern margin of the Tethys Ocean.

  20. DNA from protozoan parasites Babesia bovis, Trypanosoma cruzi, and T. brucei is mitogenic for B lymphocytes and stimulates macrophage expression of interleukin-12, tumor necrosis factor alpha, and nitric oxide. (United States)

    Shoda, L K; Kegerreis, K A; Suarez, C E; Roditi, I; Corral, R S; Bertot, G M; Norimine, J; Brown, W C


    The activation of innate immune responses by genomic DNA from bacteria and several nonvertebrate organisms represents a novel mechanism of pathogen recognition. We recently demonstrated the CpG-dependent mitogenic activity of DNA from the protozoan parasite Babesia bovis for bovine B lymphocytes (W. C. Brown, D. M. Estes, S. E. Chantler, K. A. Kegerreis, and C. E. Suarez, Infect. Immun. 66:5423-5432, 1998). However, activation of macrophages by DNA from protozoan parasites has not been demonstrated. The present study was therefore conducted to determine whether DNA from the protozan parasites B. bovis, Trypanosoma cruzi, and T. brucei activates macrophages to secrete inflammatory mediators associated with protective immunity. DNA from Escherichia coli and all three parasites stimulated B-lymphocyte proliferation and increased macrophage production of interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-alpha), and nitric oxide (NO). Regulation of IL-12 and NO production occurred at the level of transcription. The amounts of IL-12, TNF-alpha, and NO induced by E. coli and protozoal DNA were strongly correlated (r2 > 0.9) with the frequency of CG dinucleotides in the genome, and immunostimulation by DNA occurred in the order E. coli > or = T. cruzi > T. brucei > B. bovis. Induction of inflammatory mediators by E. coli, T. brucei, and B. bovis DNA was dependent on the presence of unmethylated CpG dinucleotides. However, at high concentrations, E. coli and T. cruzi DNA-mediated macrophage activation was not inhibited following methylation. The recognition of protozoal DNA by B lymphocytes and macrophages may provide an important innate defense mechanism to control parasite replication and promote persistent infection.

  1. Toxicity of Nitrate-N to Freshwater Aquatic Life and Its Water Quality Criteria%硝酸盐对淡水水生生物毒性及水质基准推导

    Institute of Scientific and Technical Information of China (English)

    张铃松; 王业耀; 孟凡生; 周岳溪; 于海斌


    为推导保护淡水水生生物的NO3-水质基准,收集了NO3-的水生生物毒性数据,然后分析了不同水生生物类群的毒性敏感性,并分别采用评价因子法、毒性百分数排序法和物种敏感度分布法进行基准值推导.结果表明,不同生物类群的水生生物对NO3-毒性的敏感性存在明显差异,其敏感性排序为节肢动物门>软体动物门>脊索动物门;甲壳纲>昆虫纲>腹足纲>双壳>两栖纲>辐鳍纲.3种基准计算方法得到的基准值存在一定差异,最终推荐采用毒性百分数排序法得出的87.97mg·L-1和5.17 mg·L-1为现阶段NO3-(以N计)的水质急性毒性和慢性毒性基准值.%The toxicity sensitivity of different freshwater aquatic organisms was analyzed using the collected toxicity data in this paper.Three methods were used to estimate the criteria of nitrate to protect the freshwater aquatic life.The results showed that the species sensitivity to nitrate followed the order of Arthropoda > Mollusca > Chordata,and Crustacea > Insecta > Gastropoda > Bivalvia >Amphibia > Actinopterygii.Moreover,the output of assessment factor method,species sensitivity distribution method and USEPA's method was significantly different.Finally,criterias of 87.97 mg·L-1 and 5.17 mg· L-1 to protect aquatic life from acute and chronic toxicity were proposed using USEPA's method.

  2. Characteristics of Karst Ecosystems of Vietnam and Their Vulnerability to Human Impact

    Institute of Scientific and Technical Information of China (English)


    Karst in Vietnam covers an area of about 60,000 km2, i.e. 18 % of the surface of the country. The country has an annual average temperature of 24 ℃, an annual average rainfall of 2300 mm and a relative humidity of about 90%. Karst in Vietnam is typified by peak cluster-depression landscapes ranging in elevation from 200 to over 2000 m. Tower and coastal karst landscapes also exit. Because of naturally favourable conditions, karst ecosystems are diverse and very rich.Higher plants (cormophytes) are abundant. They are represented by approximately 2000 species, 908 genera, 224 families,86 orders and 7 phyla. They form a thick vegetation cover of evergreen tropical rainforest. Knowledge about lower plants is limited. The fauna is rich and diverse. Phyla such as Protozoa, Vermes, Mollusca and Arthropoda are yet ill known.Preliminary results show that the phylum Chordata is represented by 541 species from 80 families, 40 orders and 5 classes.There exist many precious and rare mammals, in particular some endemic species such as Trachypithecuspoliocephalus, T.delacouri, Rhinopithecus avanculus, Rhinolophus rouxi, Seotoma dineties and Silurus cuephuongensis. The class Insecta has about 2000 species.``The fast population growth, particularly in the mountainous areas of the country, triggers an increasing demand for land and therefore threatens the ecosystem. To obtain land for farming, people have cut, burned and destroyed natural forest cover; resulting in occurrence of hazards such as soil-loss, water-loss, flash floods, mud-rock flows, rock-falls, severe drought, water logging and changes of karstic aquifers etc. Poaching precious animals and illegal logging are increasing. In contrast to other natural systems, karst ecosystems cannot be reestablished once damaged. Living karst landscapes will become rocky desert ones without life. Conservation of karstic environmental systems in general and karstic ecosystems in particular should not be the sole vocation of scientists

  3. The enigmatic mitochondrial genome of Rhabdopleura compacta (Pterobranchia reveals insights into selection of an efficient tRNA system and supports monophyly of Ambulacraria

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    Stadler Peter F


    Full Text Available Abstract Background The Hemichordata comprises solitary-living Enteropneusta and colonial-living Pterobranchia, sharing morphological features with both Chordata and Echinodermata. Despite their key role for understanding deuterostome evolution, hemichordate phylogeny is controversial and only few molecular data are available for phylogenetic analysis. Furthermore, mitochondrial sequences are completely lacking for pterobranchs. Therefore, we determined and analyzed the complete mitochondrial genome of the pterobranch Rhabdopleura compacta to elucidate deuterostome evolution. Thereby, we also gained important insights in mitochondrial tRNA evolution. Results The mitochondrial DNA of Rhabdopleura compacta corresponds in size and gene content to typical mitochondrial genomes of metazoans, but shows the strongest known strand-specific mutational bias in the nucleotide composition among deuterostomes with a very GT-rich main-coding strand. The order of the protein-coding genes in R. compacta is similar to that of the deuterostome ground pattern. However, the protein-coding genes have been highly affected by a strand-specific mutational pressure showing unusual codon frequency and amino acid composition. This composition caused extremely long branches in phylogenetic analyses. The unusual codon frequency points to a selection pressure on the tRNA translation system to codon-anticodon sequences of highest versatility instead of showing adaptations in anticodon sequences to the most frequent codons. Furthermore, an assignment of the codon AGG to Lysine has been detected in the mitochondrial genome of R. compacta, which is otherwise observed only in the mitogenomes of some arthropods. The genomes of these arthropods do not have such a strong strand-specific bias as found in R. compacta but possess an identical mutation in the anticodon sequence of the tRNALys. Conclusion A strong reversed asymmetrical mutational constraint in the mitochondrial genome of

  4. Macrobenthic fauna community in the Middle Songkhla Lake, Southern Thailand

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    Angsupanich, S.


    Full Text Available A bimonthly investigation of macrobenthic fauna at the area from Ban Pak Khat to Ban Leam Chong Thanon in the Inner Songkhla Lake from February 1998 to February 1999 was undertaken to determine the species richness and abundance. A total of 7 phyla and 161 species were identified. Annelida (58 species, Arthropoda (64 species and Mollusca (23 species were the major phyla while Nemertea (1 species, Platyhelminthes (1 species, Cnidaria (4 species and Chordata (10 species were the minor. Fifty-seven speciesof Polychaete annelids were found. The highest species richness (14 species was in the Nereididae Family, of which Ceratonereis burmensis and Namalycastis indica were predominant. Nephtys sp. and Heteromastus sp. were not so highly abundant but appeared at almost all stations through every sampling month, while Prionospio cirrifera and Pseudopolydora kempi were found in higher densities but with narrower distribution. Ficopomatus sp. and unidentified Terebellidae were not commonly found, but occasionally reached a high density. Amphipods gave the highest species richness (22 species, with Photis longicaudata distributed widely and in all months. Five species of Tanaidaceans were found with Apseudes sapensis the second most dominant (max. 5044 individuals m-2 in February in the overall fauna. Isopoda were not as densely found as tanaidaceans but there were many species (18 species. Cyathura sp.1 was the most dominant isopod. Brachidontes arcuatulus was the most dominant bivalve (max. 29449 individuals m-2 in April, especially at stations with a sand-gravel substrate. The mean density of total macrobenthic fauna among stations ranged from 920 to 10620 ind. m-2 while the monthly densities ranged from 1520 to 6160 ind.m-2. The mean density of macrobenthic fauna was highest in the dry season (April. The species richness among stations ranged from65 to 105 species while varying from 81 to 112 species during the different months. The highest species

  5. Eukaryotic community diversity and spatial variation during drinking water production (by seawater desalination) and distribution in a full-scale network

    KAUST Repository

    Belila, Abdelaziz


    Eukaryotic microorganisms are naturally present in many water resources and can enter, grow and colonize water treatment and transport systems, including reservoirs, pipes and premise plumbing. In this study, we explored the eukaryotic microbial community structure in water during the (i) production of drinking water in a seawater desalination plant and (ii) transport of the drinking water in the distribution network. The desalination plant treatment involved pre-treatment (e.g. spruce filters), reverse osmosis (RO) membrane filtration and post-treatment steps (e.g. remineralization). 454 pyrosequencing analysis of the 18S rRNA gene revealed a highly diverse (35 phyla) and spatially variable eukaryotic community during water treatment and distribution. The desalination plant feed water contained a typical marine picoeukaryotic community dominated by Stramenopiles, Alveolates and Porifera. In the desalination plant Ascomycota was the most dominant phylum (15.5% relative abundance), followed by Alveolata (11.9%), unclassified fungi clade (10.9%) and Porifera (10.7%). In the drinking water distribution network, an uncultured fungi phylum was the major group (44.0%), followed by Chordata (17.0%), Ascomycota (11.0%) and Arthropoda (8.0%). Fungi constituted 40% of the total eukaryotic community in the treatment plant and the distribution network and their taxonomic composition was dominated by an uncultured fungi clade (55%). Comparing the plant effluent to the network samples, 84 OTUs (2.1%) formed the core eukaryotic community while 35 (8.4%) and 299 (71.5%) constituted unique OTUs in the produced water at the plant and combined tap water samples from the network, respectively. RO membrane filtration treatment significantly changed the water eukaryotic community composition and structure, highlighting the fact that (i) RO produced water is not sterile and (ii) the microbial community in the final tap water is influenced by the downstream distribution system. The study

  6. The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma mansoni, and the distribution of related Pao-like elements

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    Morales Maria E


    Full Text Available Abstract Background Of the major families of long terminal repeat (LTR retrotransposons, the Pao/BEL family is probably the least well studied. It is becoming apparent that numerous LTR retrotransposons and other mobile genetic elements have colonized the genome of the human blood fluke, Schistosoma mansoni. Results A proviral form of Sinbad, a new LTR retrotransposon, was identified in the genome of S. mansoni. Phylogenetic analysis indicated that Sinbad belongs to one of five discreet subfamilies of Pao/BEL like elements. BLAST searches of whole genomes and EST databases indicated that members of this clade occurred in species of the Insecta, Nematoda, Echinodermata and Chordata, as well as Platyhelminthes, but were absent from all plants, fungi and lower eukaryotes examined. Among the deuterostomes examined, only aquatic species harbored these types of elements. All four species of nematode examined were positive for Sinbad sequences, although among insect and vertebrate genomes, some were positive and some negative. The full length, consensus Sinbad retrotransposon was 6,287 bp long and was flanked at its 5'- and 3'-ends by identical LTRs of 386 bp. Sinbad displayed a triple Cys-His RNA binding motif characteristic of Gag of Pao/BEL-like elements, followed by the enzymatic domains of protease, reverse transcriptase (RT, RNAseH, and integrase, in that order. A phylogenetic tree of deduced RT sequences from 26 elements revealed that Sinbad was most closely related to an unnamed element from the zebrafish Danio rerio and to Saci-1, also from S. mansoni. It was also closely related to Pao from Bombyx mori and to Ninja of Drosophila simulans. Sinbad was only distantly related to the other schistosome LTR retrotransposons Boudicca, Gulliver, Saci-2, Saci-3, and Fugitive, which are gypsy-like. Southern hybridization and bioinformatics analyses indicated that there were about 50 copies of Sinbad in the S. mansoni genome. The presence of ESTs

  7. 渤海湾大型底栖动物群落组成及与环境因子的关系%Community Component of Macrobenthos in Bohai Bay and Their Relationships with Environmental Factors

    Institute of Scientific and Technical Information of China (English)

    谷德贤; 刘茂利; 王娜


    The marine investigation, cluster analysis, multidimensional scaling (MDS)-, and the canonical correspondence analysis(CCA)were selected to study the community component of macrobenthos in the Bohai Bay and their relationships with environmental factors. A total of 31 macrobenthos species were collected, 8 species were polychaete, 12 species were mollusc, 4 species were crustacea, 3 species were echinoderm, 1 species was chordata, 1 species was nemertean, 1 species was echiuridae, 1 species was hemichordates. The dominant species was Potamocorbula amurensis. The average density and biomass of the macrobenthos in the Bohai Bay were 91.2 ind/m2 and 83.06 g/m2 .The cluster analysis and multidimensional scaling showed that their distribution had obvious spatial heterogeneity, 4 station groups were simply divided. CCA showed that pH, DO, depth, transparence had strong relationship with macrobenthos.%采用海上定点采样调查、等级聚类(CLUSTER)、多维排序标度(MDS)、典范对应分析(CCA)等多种方法,研究了2009年春季渤海湾大型底栖动物种类组成及其与环境因子的相关性。本次调查共采集到大型底栖动物31种,其中多毛类8种,软体动物12种,.甲壳动物4种,棘皮动物3种,脊索动物、纽形动物、蜢虫门、半索动物各1种,大型底栖动物优势种为黑龙江河蓝蛤。调查海域大型底栖动物的平均密度为91.2个/m2,平均生物量为83.06g/m2。CLUSTER和MDS分析表明,大型底栖动物的分布具有显著的空间差异性,依此将大型底栖动物简单地分为4个群落。CCA分析显示,pH、溶解氧、透明度、水深与大型底栖动物分布的相关性较大。

  8. Evidence for stasis and not genetic piracy in developmental expression patterns of Branchiostoma lanceolatum and Branchiostoma floridae, two amphioxus species that have evolved independently over the course of 200 Myr. (United States)

    Somorjai, Ildiko; Bertrand, Stéphanie; Camasses, Alain; Haguenauer, Anne; Escriva, Hector


    Cephalochordates, the most basal extant group in the phylum Chordata, are represented chiefly by about 20 species of the genus Branchiostoma, commonly called amphioxus or lancelets. In recent years, insights into the evolutionary origin of the vertebrates have been gained from molecular genetic studies during the development of three of these amphioxus species (Branchiostoma floridae in North America, Branchiostoma lanceolatum in Europe, and Branchiostoma belcheri in East Asia). In spite of an estimated divergence time of 100-200 Myr among these species, all three are remarkably similar morphologically, and students of amphioxus have tacitly assumed that such resemblances arise during ontogeny from nearly identical networks of developmental genes. We felt that this assumption needed to be reexamined because instances are known--even in comparisons of closely related species--where characters seeming homologous on the basis of morphology actually develop under the control of conspicuously divergent genetic programs (a phenomenon termed "genetic piracy"). In the present work, we tested the hypothesis that morphological similarities reflect strict conservation of developmentally important genes' expression patterns in order to assess whether the developmental genetics of different amphioxus species show evidence of genetic piracy. To these ends, we cloned 18 genes implicated in different developmental functions in B. lanceolatum and compared their gene expression patterns with the known expression patterns of their orthologous genes in B. floridae. We show that, for the most part, conservation of gene expression parallels that of morphology in these two species. We also identified some differences in gene expression, likely reflecting experimental sensitivity, with the exception of Pax1/9, which may result from true developmental specificities in each amphioxus species. Our results demonstrate that morphological conservation reflects stasis in developmental gene

  9. Antifracture efficacy of currently available therapies for postmenopausal osteoporosis. (United States)

    Reginster, Jean-Yves


    3-year number needed to treat values of between 9 and 21 for vertebral fracture and from 48 upwards for hip fracture. International guidelines agree that agents that have been shown to decrease vertebral, nonvertebral and hip fractures should be used preferentially over agents that only demonstrate vertebral antifracture efficacy. This is the case for alendronate, risedronate, zoledronic acid, denosumab and strontium ranelate. Finally, therapeutic decisions should be based on a balance between benefits and risks of treatment, which must be carefully considered in each particular case both by the physician and the patient. Indeed, no single agent is appropriate for all patients and, therefore, treatment decisions should be made on an individual basis, taking into account all measures of treatment effect and risk before making informed judgments about the best individual treatment option.

  10. [Treatment of osteoporosis: current data and prospects]. (United States)

    Reginster, J Y; Deroisy, R; Franchimont, P


    Postmenopausal osteoporosis is characterized not only by a reduction in bone mass but also by bone microarchitecture alterations, which result in greater bone frailty and in an increased fracture risk. Many drugs have been studied to determine whether they prevent bone loss or reduce the incidence of additional fractures in patients with established osteoporosis. Primary prevention of osteoporosis rests on regular exercising and adequate intake of dietary calcium. For secondary prevention in women undergoing menopause, replacement estrogen therapy given for at least ten years is associated with substantial reductions in fractures of the radius, hip, and spine. Other drugs capable of arresting postmenopausal bone loss include parenteral, nasal or rectal calcitonin and diphosphonates. However, the long-term safety of the latter requires further evaluation. Current studies are evaluating new molecules with potential preventive efficacy, such as ipriflavone. There is no general consensus about the efficacy of treatments for established osteoporosis with fractures. To date, no controlled studies have demonstrated a reduction in the incidence of further fractures in patients given calcium alone. Studies of hydroxylated vitamin D derivatives have been disappointing, although daily administration of vitamin D3 in combination with calcium significantly reduced the incidence of nonvertebral fractures in a population of elderly institutionalized subjects. Plausible explanations for this effect include increased vitamin D levels and reduced parathyroid levels in the bloodstream. Parenteral or nasal calcitonin stabilizes or increases bone mineral content in both cancellous and cortical bone. This effect is especially marked in high-turn-over patients. Several lines of evidence suggest that calcitonin therapy has a protective effect against vertebral and hip fractures. In patients with osteoporosis, oral or intravenous diphosphonates are associated with a significant increase in

  11. Strategies for treatment to prevent fragility fractures in postmenopausal women. (United States)

    Geusens, Piet


    The objective of treatment of osteoporosis is to decrease the risk of fractures in patients at high risk for a first or subsequent fracture. The efficacy of treatment will depend on the efficiency and level of implementation of clinical case finding to select patients at risk, the results of additional investigations, the efficacy, tolerance and safety of medical intervention and the adherence to treatment during follow-up. Each of these steps is critical in treatment in daily practice. Failure to consider one or another step can result in suboptimal fracture prevention or overtreatment. The aim of case finding is to identify patients for treatment, who have disease characteristics of patients in whom fracture prevention has been demonstrated in randomised controlled trials (RCTs). These include patients with a low-trauma hip or vertebral fracture, with a low bone mineral density (BMD) or with a high risk of fracture based on the presence of clinical risk factors (CRFs) for osteoporosis and fractures such as included in the FRAX case-finding algorithm, with or without BMD. Case finding starts clinically, with systematic or opportunistic doctor- and/or patient-driven evaluation for the presence of CRFs, but its implementation is low. Further investigations aim to assess the risk of fracture(s) and to have baseline measurements for the subsequent monitoring of treatment, to exclude diseases that mimic osteoporosis, to identify the cause of osteoporosis and contributory factors and to select the most appropriate treatment. Medical intervention consists of providing information about osteoporosis to the patient, lifestyle advice, optimalisation of calcium intake and vitamin D status, fall prevention to reduce fall risk, correction of reversible contributors to secondary osteoporosis and a wide array of drugs for prevention of a first or subsequent vertebral, hip and non-vertebral, non-hip fracture. Drug treatment is based on manipulation of bone remodelling by

  12. Long-term efficacy, safety, and patient acceptability of ibandronate in the treatment of postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    Inderjeeth CA


    Full Text Available Charles A Inderjeeth,1,2 Paul Glendenning,2,3 Shoba Ratnagobal,1 Diren Che Inderjeeth,1 Chandni Ondhia1 1Department of Geriatric Medicine and Rheumatology, North Metropolitan Health Service, 2School of Medicine and Pharmacology, University of Western Australia, 3Department of Clinical Biochemistry, PathWest Royal Perth Hospital, Perth, WA, Australia Abstract: Several second-generation bisphosphonates (BPs are approved in osteoporosis treatment. Efficacy and safety depends on potency of farnesyl pyrophosphate synthase (FPPS inhibition, hydroxyapatite affinity, compliance and adherence. The latter may be influenced by frequency and route of administration. A literature search using “ibandronate”, “postmenopausal osteoporosis”, “fracture”, and “bone mineral density” (BMD revealed 168 publications. The Phase III BONE study, using low dose 2.5 mg daily oral ibandronate demonstrated 49% relative risk reduction (RRR in clinical vertebral fracture after 3 years. Non-vertebral fracture (NVF reduction was demonstrated in a subgroup (pretreatment T-score ≤ -3.0; RRR 69% and a meta-analysis of high annual doses (150 mg oral monthly or intravenous equivalent of ibandronate; RRR 38%. Hip fracture reduction was not demonstrated. Long-term treatment efficacy has been confirmed over 5 years. Long term safety is comparable to placebo over 3 years apart from flu-like symptoms which are more common with oral monthly and intravenous treatments. No cases of atypical femoral fracture or osteonecrosis of the jaw have been reported in randomized controlled trial studies. Ibandronate inhibits FPPS more than alendronate but less than other BPs which could explain rate of action onset. Ibandronate has a higher affinity for hydroxyapatite compared with risedronate but less than other BPs which could affect skeletal distribution and rate of action offset. High doses (150 mg oral monthly or intravenous equivalent were superior to low doses (oral 2.5 mg daily

  13. Bisphosphonates for the prevention and treatment of osteoporosis in patients with rheumatic diseases: a systematic review and meta-analysis.

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    Zhiyun Feng

    Full Text Available BACKGROUND: While bisphosphonates (BPs are commonly used in clinical treatment for osteoporosis, their roles on osteoporosis treatment for rheumatic patients remain unclear. We performed a meta-analysis to evaluate the efficacy of BPs on fractures prevention and bone mass preserving in rheumatic patients. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials for relevant literatures with a time limit of Jan. 6, 2012. All randomized clinical trials of BPs for adult rheumatic patients with a follow-up of 6 months or more were included. We calculated relative risks (RRs for fractures and weighted mean difference (WMD for percent change of bone mineral density (BMD. Twenty trials were included for analysis. The RR in rheumatic patients treated with BPs was 0.61 (95%CI [0.44, 0.83], P = 0.002 for vertebral fractures, and 0.49 (95%CI [0.23, 1.02], P = 0.06 for non-vertebral fractures. The WMD of BMD change in the lumbar spine was 3.72% (95%CI [2.72, 4.72], P<0.001 at 6 months, 3.67% (95%CI [2.84, 4.50], P<0.001 at 12 months, 3.64% (95%CI [2.59, 4.69], P<0.001 at 24 months, and 5.87% (95%CI [4.59, 7.15], P<0.001 at 36 months in patients using BPs, as compared with those treated with calcium, vitamin D or calcitonin. In subgroup analyses, rheumatic patients using BPs for osteoporosis prevention had greater WMD than those using BPs for treating osteoporosis at 6 months (4.53% vs. 2.73%, P = 0.05 and 12 months (4.93% vs. 2.91%, P = 0.01. CONCLUSIONS/SIGNIFICANCE: In both short-term and middle-term, BPs can preserve bone mass and reduce the incidence of vertebral fractures in rheumatic patients, mainly for those who have GC consumption. The efficacy of BPs is better when using BPs to prevent rather than to treat osteoporosis in rheumatic patients.

  14. Organization and post-transcriptional processing of focal adhesion kinase gene

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    Enslen Hervé


    Full Text Available Abstract Background Focal adhesion kinase (FAK is a non-receptor tyrosine kinase critical for processes ranging from embryo development to cancer progression. Although isoforms with specific molecular and functional properties have been characterized in rodents and chicken, the organization of FAK gene throughout phylogeny and its potential to generate multiple isoforms are not well understood. Here, we study the phylogeny of FAK, the organization of its gene, and its post-transcriptional processing in rodents and human. Results A single orthologue of FAK and the related PYK2 was found in non-vertebrate species. Gene duplication probably occurred in deuterostomes after the echinoderma embranchment, leading to the evolution of PYK2 with distinct properties. The amino acid sequence of FAK and PYK2 is conserved in their functional domains but not in their linker regions, with the absence of autophosphorylation site in C. elegans. Comparison of mouse and human FAK genes revealed the existence of multiple combinations of conserved and non-conserved 5'-untranslated exons in FAK transcripts suggesting a complex regulation of their expression. Four alternatively spliced coding exons (13, 14, 16, and 31, previously described in rodents, are highly conserved in vertebrates. Cis-regulatory elements known to regulate alternative splicing were found in conserved alternative exons of FAK or in the flanking introns. In contrast, other reported human variant exons were restricted to Homo sapiens, and, in some cases, other primates. Several of these non-conserved exons may correspond to transposable elements. The inclusion of conserved alternative exons was examined by RT-PCR in mouse and human brain during development. Inclusion of exons 14 and 16 peaked at the end of embryonic life, whereas inclusion of exon 13 increased steadily until adulthood. Study of various tissues showed that inclusion of these exons also occurred, independently from each other, in a

  15. Design and baseline characteristics of a prospective cohort study for determinants of osteoporotic fracture in community-dwelling elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN Study

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    Moon Jong-Seong


    Full Text Available Abstract Background Osteoporosis and osteoporotic fracture in men are significant public health problems in an aging society. However, information on male osteoporosis remains impressively lacking, especially for Asians. We designed the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN study as an ancillary study of a cohort study, the Fujiwara-kyo study, to determine risk factors for osteoporotic fractures in Japanese men. Methods/Design Design: A community-based single-centre prospective cohort study with at least a 5-year follow-up Subjects: All the male participants of the Fujiwara-kyo study who were living in the four cities studied, aged 65 years and older, and able to walk without aid from others. Primary outcome: Incidence of osteoporotic fractures including vertebral and clinical non-vertebral fractures. Additional outcomes: Change in bone mineral density (BMD, change in hip geometry, onset of receiving benefits from Long-term Care Insurance (LCI, health-related quality of life, and mortality. Baseline measurements: BMD at the lumbar spine (LS and hip (TH, hip geometry, vertebral deformity assessment, bone turnover markers, physical and cognitive performance, various medical and lifestyle factors, and geriatric psychosocial measures confirmed by interviews based on self-administrated questionnaires. Outcome surveillance: Annual mail surveys and a follow-up survey at the fifth year comprising similar items to the baseline study will be used to determine the outcomes. Receipt of benefits from LCI and mortality will be obtained from the city governments. Current status: The baseline study was conducted for 2174 eligible men, and 2012 completed the study and were eligible for follow-up. Prevalence rates of osteoporosis (BMD 2.5 SD or more below the young adult mean (YAM and low BMD (BMD 1 SD or more below YAM in at least one of LS and TH were calculated to be 4.4% and 41.8%, respectively. The proportion of men with low BMD only at TH showed a

  16. The Epigenome of Schistosoma mansoni Provides Insight about How Cercariae Poise Transcription until Infection.

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    David Roquis

    Full Text Available Chromatin structure can control gene expression and can define specific transcription states. For example, bivalent methylation of histone H3K4 and H3K27 is linked to poised transcription in vertebrate embryonic stem cells (ESC. It allows them to rapidly engage specific developmental pathways. We reasoned that non-vertebrate metazoans that encounter a similar developmental constraint (i.e. to quickly start development into a new phenotype might use a similar system. Schistosomes are parasitic platyhelminthes that are characterized by passage through two hosts: a mollusk as intermediate host and humans or rodents as definitive host. During its development, the parasite undergoes drastic changes, most notable immediately after infection of the definitive host, i.e. during the transition from the free-swimming cercariae into adult worms.We used Chromatin Immunoprecipitation followed by massive parallel sequencing (ChIP-Seq to analyze genome-wide chromatin structure of S. mansoni on the level of histone modifications (H3K4me3, H3K27me3, H3K9me3, and H3K9ac in cercariae, schistosomula and adults (available at We saw striking differences in chromatin structure between the developmental stages, but most importantly we found that cercariae possess a specific combination of marks at the transcription start sites (TSS that has similarities to a structure found in ESC. We demonstrate that in cercariae no transcription occurs, and we provide evidences that cercariae do not possess large numbers of canonical stem cells.We describe here a broad view on the epigenome of a metazoan parasite. Most notably, we find bivalent histone H3 methylation in cercariae. Methylation of H3K27 is removed during transformation into schistosomula (and stays absent in adults and transcription is activated. In addition, shifts of H3K9 methylation and acetylation occur towards upstream and downstream of the transcriptional start site (TSS. We conclude

  17. Effects of 16-month treatment with the cathepsin K inhibitor ONO-5334 on bone markers, mineral density, strength and histomorphometry in ovariectomized cynomolgus monkeys. (United States)

    Yamada, Hiroyuki; Ochi, Yasuo; Mori, Hiroshi; Nishikawa, Satoshi; Hashimoto, Yasuaki; Nakanishi, Yasutomo; Tanaka, Makoto; Bruce, Mark; Deacon, Steve; Kawabata, Kazuhito


    We examined the effects of ONO-5334, a cathepsin K inhibitor, on bone markers, BMD, strength and histomorphometry in ovariectomized (OVX) cynomolgus monkeys. ONO-5334 (1.2, 6 and 30mg/kg/day, p.o.), alendronate (0.05mg/kg/2weeks, i.v.), or vehicle was administered to OVX monkeys (all groups N=20) for 16months. A concurrent Sham group (N=20) was also treated with vehicle for 16months. OVX significantly increased bone resorption and formation markers and decreased BMD in lumbar vertebra, femoral neck, proximal tibia and distal radius. Alendronate suppressed these parameters to a level similar to that in the Sham-operated monkeys. ONO-5334 at doses 6 and 30mg/kg decreased bone resorption markers to a level roughly half of that in the Sham group, while keeping bone formation markers level above that in the Sham monkeys. Changes in DXA BMD confirmed that ONO-5334 at doses 6 and 30mg/kg increased BMD to a level greater than that in the Sham group in all examined sites. In the proximal tibia, in vivo pQCT analysis showed that ONO-5334 at doses 6 and 30mg/kg suppressed trabecular BMD loss to the sham level. However, ONO-5334 increased cortical BMD, cortical area and cortical thickness to a level greater than that in the Sham group, suggesting that ONO-5334 improves both cortical BMD and cortical geometry. Histomorphometric analysis revealed that ONO-5334 suppressed bone formation rate (BFR) at osteonal site in the midshaft femur but did not influence OVX-induced increase in BFR at either the periosteal or endocortical surfaces. Unlike alendronate, ONO-5334 increased osteoclasts surface (Oc.S/BS) and serum tartrate-resistant acid phosphatise 5b (TRAP5b) activity, highlighting the difference in the mode of action between these two drugs. Our results suggest that ONO-5334 has therapeutic potential not only in vertebral bones, but also in non-vertebral bones.

  18. 真核生物DNA连接酶Ⅲ的功能演化%Functional evolution of Eukaryote DNA ligase Ⅲ

    Institute of Scientific and Technical Information of China (English)

    靳春艳; 盛自章; 黄京飞


    DNA连接酶Ⅲ被认为只存在于脊椎动物,并在细胞核DNA的修复和线粒体DNA的复制和修复过程中发挥功能.虽然近来有关于无脊椎动物中存在着DNA连接酶Ⅲ的报道,但其功能演化及在无脊椎动物中的分布仍不清楚.为进一步探讨DNA连接酶Ⅲ的功能演化,进行了数据库搜索、线粒体定位信号(MLS)预测和功能位点保守性分析等.研究结果显示:DNA连接酶Ⅲ在变形虫、动物界和领鞭毛虫中广泛存在,但其在真菌界等发生整个蛋白或部分结构域的丢失;很多物种的DNA连接酶Ⅲ不含线粒体定位信号,因此,它们不太可能在线粒体中发挥作用,而参与细胞核DNA的修复是DNA连接酶Ⅲ较为古老和保守的功能.%Previous studies revealed that DNA ligase III was restricted to vertebrates and functioned in nucleus DNA repair and mitochondria DNA replication and repair. Although recent researches have reported that DNA ligase m is also found in non-vertebrates, little attention has been devoted to the distribution and functional evolution of DNA ligase III. To probe the functional evolution of DNA ligase III , database searches, mitochondrial localization signal prediction (MLS) and functional conservation analysis were performed. The results show that, DNA ligase III can be observed in amoebozoa, metazoa and choanoflagellates, but the whole protein or some domains are lost in some species including fungi. The MLS prediction analysis suggests that, the DNA ligase III in many species can not function in mitochondria, and is consequently less likely to play a role for DNA ligase III in mitochondria. The conservation analyses of functional site demonstrate that nucleus DNA repair is an ancient and conserved function of DNA ligase III.

  19. PTH-analogs: comparable or different? (United States)

    Verhaar, H J J; Lems, W F


    Because no comparative studies exist, no clear pronouncements can be made about the potential differences in effectiveness and safety between PTH 1-34 and PTH 1-84. As regards the efficacy, a convincing reduction of vertebral fractures was shown in both cases [Neer, R.M., Arnaud, C.D., Zanchetta, J.R., Prince, R., Gaich, G.A., Reginster, J.Y., Hodsman, A.B., Eriksen, E.F., Ish-Shalom, S., Genant, H.K., Wang, O., Mitlak, B.H., 2001. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N. Engl. J. Med. 344, 1434-1441; Greenspan, S.L., Bone, H.G., Ettinger, M.P., Hanley, D.A., Lindsay, R., Zanchetta, J.R., Blosch, C.M., Mathisen, A.L., Morris, S.A., Marriott, T.B., Treatment of Osteoporosis with Parathyroid Hormone Study Group, 2007. Effect of recombinant human parathyroid hormone (1-84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann. Intern. Med. 146, 326-339]. A reduction of non-vertebral fractures was shown in the case of PTH 1-34 only. Another significant resemblance is that both medicines have a strong anabolic action; this mechanism of action is essentially different from the bisphosphonates and strontium ranelate. Both medicines constitute a welcome addition to the therapeutic arsenal for patients with severe osteoporosis. More data from literature (including information on follow-up data and use in men) are available for PTH 1-34 because it has been available for longer. As regards the side effect profile, PTH 1-84 appears to have a higher incidence of hypercalcemia, hypercalciuria and nausea than teriparatide. Here, too, no comparative study exists: the differences may therefore be based on an actual difference in side effects, or it may be ascribed to differences in definitions and/or patient populations.

  20. 河北昌黎生态监控区8月潮间带生物多样性年际变化趋势%The inter-annual variation trend of intertidal biodiversity in August in the ecology-monitoring area of Changli in Hebei

    Institute of Scientific and Technical Information of China (English)

    张月明; 梁晓林; 赵志楠; 韩晓庆; 金照光; 高伟明


    According to the monitoring data and information obtained from National Marine Environmental Monitoring Center, the species composition, density, biomass, dominant species andthe trend of biodiversity variation in the ecology-monitoring area of Changli in Hebei Province from 2009 to 2013 were analyzed. The results showed that 5 phylum including arthropods, annelid, mollusks, echinodermata and chordata, totally 17 family and 26 species were identified. The types and number of species were declined annually. The density and biomass were consistent with the characteristics of low tidal zone>medium tidal zone>high tidal zone. The dominant species were changed significantly, by which arthropods, annelid and mollusks appearing alternately. As the decreasing of the number of dominant species, the dominance index went up which suppressed the other species. The Shannon-Wiener’s index(H’), Margalef’s richness index (dMa) were low, and their variation ranges were 0.81~3.23 and 0.48~3.96, respectively. The variation range of Pielou’s evenness index (J) was0.64~0.8, which presented a miniature uptrend and stable status.%依据国家海洋环境监测中心2009~2013年测得的数据和资料,对河北昌黎生态监控区潮间带生物的种类组成、栖息密度、生物量、优势种以及多样性指数进行统计运算,分析该监控区5年时间尺度的潮间带生物多样性变化趋势。结果表明:监控区共鉴定出潮间带生物5门,包括节肢动物、环节动物、软体动物、棘皮动物和脊索动物,共17科,26种,类型较少,年际种数呈逐年下降趋势;栖息密度与生物量较低,保持低潮带>中潮带>高潮带的特征;优势种群变化显著,节肢动物、环节动物和软体动物交替出现,优势种数逐年减少,优势度上升,对其他物种抑制作用增强;均匀度指数(J)呈微上升趋势,变化范围为0.64~0.81,状况良好,物种多样性指数(H′)和丰富度指数(d

  1. Nearly complete rRNA genes from 371 Animalia: updated structure-based alignment and detailed phylogenetic analysis. (United States)

    Mallatt, Jon; Craig, Catherine Waggoner; Yoder, Matthew J


    This study presents a manually constructed alignment of nearly complete rRNA genes from most animal clades (371 taxa from ~33 of the ~36 metazoan phyla), expanded from the 197 sequences in a previous study. This thorough, taxon-rich alignment, available at and in the Dryad Repository (doi:, is based rigidly on the secondary structure of the SSU and LSU rRNA molecules, and is annotated in detail, including labeling of the erroneous sequences (contaminants). The alignment can be used for future studies of the molecular evolution of rRNA. Here, we use it to explore if the larger number of sequences produces an improved phylogenetic tree of animal relationships. Disappointingly, the resolution did not improve, neither when the standard maximum-likelihood method was used, nor with more sophisticated methods that partitioned the rRNA into paired and unpaired sites (stem, loop, bulge, junction), or accounted for the evolution of the paired sites. For example, no doublet model of paired-site substitutions (16-state, 16A and 16B, 7A-F, or 6A-C models) corrected the placement of any rogue taxa or increased resolution. The following findings are from the simplest, standard, ML analysis. The 371-taxon tree only imperfectly supported the bilaterian clades of Lophotrochozoa and Ecdysozoa, and this problem remained after 17 taxa with unstably positioned sequences were omitted from the analysis. The problem seems to stem from base-compositional heterogeneity across taxa and from an overrepresentation of highly divergent sequences among the newly added taxa (e.g., sequences from Cephalopoda, Rotifera, Acoela, and Myxozoa). The rogue taxa continue to concentrate in two locations in the rRNA tree: near the base of Arthropoda and of Bilateria. The approximately uncertain (AU) test refuted the monophyly of Mollusca and of Chordata, probably due to long-branch attraction of the highly

  2. Study of the Intertidal Macrobenthic Fauna in Dayushan Island, Zhejiang%浙江大渔山岛潮间带大型底栖动物的群落结构

    Institute of Scientific and Technical Information of China (English)



    The community structures of the intertidal macrobenthic fauna in Dayushan island,Zhejiang,including species composition,quantity distribution and biodiversity,were analyzed in the study.The investigation in the study found 35 species,including 1 species of Annelida,2 species of Chordata,2 species of coelenterate,9 species of Arthropoda and 21 species of Mollusca.The average biomass and density in all stations were 1027.33 g/m2 and 1404 ind.m-2,respectively.The mollusca were the first in biomass and density among all macrobenthic fauna.The value of Shannon-Weaner index,Margalef's species richness index and Pielou's evenness index were 0.193~2.101,0.268~1.744 and 0.073~2.007,and their averages were 1.140±1.084,1.080±0.696 and 0.780±0.886,respectively.There was significant difference between the results in the study and in the similar experiments.The Abundance/Biomass curves of the intertidal zone of Dayushan island had part of the cross.%文章通过分析浙江大渔山岛潮间带大型底栖动物的物种组成、数量分布和生物多样性等群落结构特征来了解周围海域的水质状况。本次大渔山岛海域潮间带调查采获的大型底栖动物标本共有35种,其中软体动物21种,节肢动物9种,脊索动物与腔肠动物各2种,环节动物仅1种。且该海域潮间带大型底栖动物的平均生物量为1027.33 g/m2,平均丰度为1404 ind./m2。在各类群底栖动物中,软体动物的平均生物量及丰富都为第一。大渔山岛潮间带大型底栖动物的多样性指数、丰富度指数和均匀度指数的分布范围分别在0.193~2.101、0.268~1.744和0.073~2.007,平均值分别为1.140±1.084、1.080±0.696和0.780±0.886。

  3. Effects of the anti-receptor activator of nuclear factor kappa B ligand denusomab on beta thalassemia major-induced osteoporosis

    Directory of Open Access Journals (Sweden)

    Mohamed A Yassin


    Full Text Available Introduction: Osteoporosis represents the second most common cause of endocrinopathy in patients with beta thalassemia major (BTM. Some drugs proved effective to reduce vertebral and non-vertebral fracture risk. Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor kappa B ligand (RANKL, a member of the tumor necrosis factor receptor superfamily essential for osteoclastogenesis. The efficacy and safety of denosumab in BTM-induced osteoporosis has not been tested. Objective: To evaluate the efficacy and safety of anti-RANKL on the biochemical and radiological parameters of bone mineralization in patients with BTM-induced osteoporosis. Design: The study population was selected using the random sampling method from the patient′s database of our thalassemia clinic. Transfusion-dependent BTM patients above 18 years with no history of treatment with bisphosphonates were randomly selected. Bone mineral density (BMD of the lumbar spine (LS and right femoral neck (FN were measured by dual energy X-ray absorption (DEXA scan using a calibrated method. Independent factors likely to be associated with low bone mass were determined and included in the analysis to ascertain possible associations. Patients and Methods: We studied 30 patients with BTM-induced osteoporosis as per World Health Organization criteria (T Score of less than − 1.0 being defined as osteopenic and a T Score of less than − 2.5 being referred as osteoporotic. 19 males and 11 females aged between 18 and 32 years, with full pubertal development (Tanner′s stage 5 at the time of the study. Their mean serum ferritin concentration was 3557 ng ± 1488 ng/ml. Every patient underwent DEXA scan as a baseline and after 12 months of denosumab therapy. Biochemical evaluation including serum concentrations of creatinine, Na, K, calcium, phosphorus, parathormone, bone specific alkaline phosphatase and type 1 collagen carboxy telopetide (ICCT using enzyme

  4. Intervensjonsstudien "Forebyggelse av lårhalsbrudd". Metode og praktisk gjennomføring

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    Elisabeth Kvaavik


    Full Text Available  Bakgrunn  3 kan forebygge brudd blant sykehjemsbeboere. Her beskrivesmetoden og den praktiske gjennomføringen av studien.Metode  mg vitamin D daglig som 5 ml tran og kontrollgruppa fikk 5 ml tran der vitamin D var fjernet. Endepunktenevar lårhalsbrudd og alle ikke-vertebrale brudd. Et enkelt studieopplegg ble vektlagt. På bakgrunnav styrkeberegningen var målsetningen å inkludere ca. 2000 deltakere.Resultater  Konklusjon  The intervention study”Prevention of hip fractures”. Nor J Epidemiol 2000; 10 (1: 79-85.  Background  3 can prevent suchfractures. Here we present the method and the implementation of the study.Method  mg vitamin D daily in 5 ml cod liver oil for 2 years and the control group received 5 ml cod liver oilwithout vitamin D. The endpoints were hip fractures and all non-vertebral fractures. It was consideredimportant to use a trial that the nursing homes would find easy to implement. According to power calculationthe aim was to include about 2000 participants.Results  Conclusion  : The participation was lower than expected as recruiting nursing homes and nursing homeresidents posed considerable difficulty. However, the great majority of the ward staff at the participatingwards did not find the intervention demanding. A total of 1144 was included in the study.: A total of 1144 residents from 51 nursing homes (of 106 invited in Oslo, Lier and Bergen participated.The participation rate at the individual nursing home varied from 3 to 57%. The participants were85 years old and 3/4 were women. Mean calcium intake from cheese and milk was 450 mg/day, more than40% used a vitamin D supplement while only 3% used a calcium supplement. 1/3 of the participants completedthe 2 years intervention, about 1/3 finished the intervention before 2 years because of death and 1/3finished before 2 years of other causes. The great majority of the wards did not find the interventiondemanding.: A randomised, double

  5. Management of postmenopausal osteoporosis and the prevention of fractures. (United States)

    Gambacciani, M; Levancini, M


    Postmenopausal osteoporosis affects millions of women, being estrogen deficiency the key factor in the pathogenesis of involutional osteoporosis. Fracture prevention is one of the public health priorities worldwide. Different treatments for osteoporosis are available. The various options are aimed to maintain bone health and decrease the risk of fractures. The majority of these drugs are antiresorptive agents, i.e., drugs that lower bone turnover, inhibiting osteoclastic bone resorption. Dietary sources of calcium intake and vitamin D are ideal, while pharmachological supplements should be used if diet alone cannot provide the recommended daily intake. Bisphosphonates are first-line therapy for patients with established osteoporosis at high risk of fracture. Some serious, but rare, adverse events have been associated with their long-term administration. The monoclonal antibody to RANKL, named denosumab, administered as a 60-mg subcutaneous injection every 6 months, is a valuable option for the treatment of postmenopausal osteoporosis in women at increased or high risk of fractures, who are unable to take other osteoporosis treatments. Teriparatide (PTH 1-34) is the only available osteoanabolic drugs for osteoporosis treatment at present. Its use is limited to severe osteoporosis because of the high cost of the treatment. In climacteric women, in different stages of menopausal transition, and beyond, hormone replacement therapy at different doses (HRT) rapidly normalizes turnover, preventing and/or treating osteoporosis. HRT is able to preserve and even increase BMD at all skeletal sites, leading to a significant reduction in vertebral and non-vertebral fractures. Selective estrogen modulators (SERMs) as raloxifene and bazedoxifene reduce bone turnover and maintains or increases vertebral and femoral BMDs in comparison to placebo and reduces the risk of vertebral and new vertebral fractures, in high risk women. The combination of a SERM with an estrogen has been


    Directory of Open Access Journals (Sweden)

    Carlos G. Musso


    Full Text Available Introduction: Since between 25-30% bone fractures, and 60% hip fractures in the general population are common in the subgroup which correspond to very old women. This happens due to the high predominance of primary osteoporosis and the incidence of falls which are characteristic of such group; thus, we have decided to investigate, through a systematic revision of the bibliography, the value of strontium in the prevention of bone fractures caused by falls in very old patients who suffer from primary osteoporosis. Material and Method: A systematic revision of the literature was carried out following the recommendations of the Cochrane methodology. Out of the 8 documents initially recovered, only two were included (2 independent reviewers selected, evaluated and extracted the data from the included tests since such tests were the only ones which complied with the eligibility criteria to be tests performed on a population of very old patients: older than 74 years old, thus reaching a total amount of 2616 patients who took part in this test. Results: Despite the abundance of information in favour of the treatment using strontium, there is a relative risk in the case of non-vertebral fractures one year after treatment which goes through unit: 0.58 [0.32, 1.06]. Regarding the risk of fracture at the hip level, there are certain differences when it is compared with the aforementioned data. On the one hand, the reduction of the risk of fractures (32% after 3 years of treatment with strontium ranelate documented by the Seeman test 2006 did not reach statistical significance (p=0.112, and its relative risk goes through unit: 0.68 [0.45, 1.05] Nevertheless, the Reginster 2008 test showed that after 5 years of treatment with strontium ranelate there was a bigger reduction (43% which was statistically significant (p=0.036 (Tables 1 and 4. Such data could mean that the hip bone may need a longer period of exposure to strontium to benefit from an effective

  7. Efectos "in vivo" de Metformina sobre las alteraciones de la microarquitectura sea asociadas al Sndrome Metablico inducido por fructosa en ratas In vivo effects of Metformin on the alterations of bone micro-architecture associated with fructose-induced Metabolic Syndrome in rats

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    J.I Felice


    Full Text Available El Sndrome Metablico (SM se ha asociado recientemente con una disminucin en la densidad mineral sea, y con un aumento en la incidencia de fracturas osteoporticas. Recientemente encontramos que la Metformina por va oral en ratas, promueve la diferenciacin osteognica de clulas progenitoras de mdula sea e incrementa la reparacin de lesiones seas. En este trabajo evaluamos los efectos del SM inducido por Fructosa sobre la microarquitectura sea en ratas, y la modulacin de estos efectos por Metformina administrada en forma oral. Utilizamos ratas Sprague Dawley macho jvenes: C (control sin tratamiento, C+M (100mg/kg/da Metformina en el agua de bebida, F (10 % Fructosa en el agua de bebida y F+M (Fructosa+Metformina en el agua de bebida. Los tratamientos se continuaron por 3 semanas luego de lo cual se tomaron muestras de sangre, previas al sacrificio de los animales. Se disecaron los fmures para evaluacin histomorfomtrica de la microarquitectura metafisaria por tincin con Hematoxilina-Eosina (H-E. Se observ un incremento en la glucemia y trigliceridemia en el grupo F versus el C, compatible con el desarrollo de SM. El anlisis de las metfisis femorales mostr un aumento en la densidad osteoctica trabecular para el grupo C+M (118 % del control, pSeveral clinical studies have demonstrated that the Metabolic Syndrome (MS is associated with a decrease in bone mineral density, and with an increased risk for non-vertebral osteoporotic fractures. We have recently found that orally administered Metformin induces osteogenic effects in rats, promoting osteoblastic differentiation of bone marrow progenitor cells and increasing the repair of bone lesions. In the present work we have evaluated the effects of Fructose-induced MS on bone micro-architecture in rats, and the possible modulation of these effects by orally administered Metformin. We utilized young male Sprague-Dawley rats, divided into four groups: C (non-treated controls; C+M (100 mg/kg/day of Metformin


    Institute of Scientific and Technical Information of China (English)

    王敏晓; 程方平; 李超伦; 孙松


    Estimation of zooplankton diversity and distribution is important for understanding local marine ecosystem conditions,and may serve as sensitive indicators for climate-induced changes.The scarcity of taxonomists and subtle morphological variations in some groups pose a problem for the identification of zooplanktons,especially at their larval stages.DNA barcodes provide an alternative approach to accurate identification of zooplankton species.The efficiency of the mitochondrial cox1 fragments for species reorganization in zooplanktons was evaluated in this study.The samples were collected from the Jiaozhou Bay and a station in the South Yellow Sea.82 DNA barcodes were determined for 45 common species that belonged to six different phyla in the local region,including:Arthropoda,Chaetognatha,Chordata,Cnidaria,Echinodermata,and Mollusca.According to the saturation plot,the cox1 gene was substitutionally saturated for the alignment,which was best illustrated by the wobble codons of the gene.The wobble codons quickly got saturated at around 0.2 substitution per site.K2P genetic distances between individuals within the same species ranged from 0 to 0.11,with an average of 0.013(SE = 0.003);meanwhile,genetic distance between species within the same genera ranged from 0.137 to 0.369,with an average of 0.265(SE = 0.002).Thus the genetic distance between species was at least 20 times larger that of the within species,indicating a barcode gap,which ensured that cox1 sequences can be used as reliable characters for species identification for the zooplankton assemblages.However,species with extremely large intraspecific divergences were still noticed in our study,which may be explained by population genetic divergence owing to ecological or geographical isolation,unidentified cryptic speciation,and mis-identification.The significant barcode gap and the long-branch isolated shallow tips topology for the Sagitta bedoti suggested a possible cryptic speciation for the

  9. 泉州湾洛阳江口2种红树林生境大型底栖动物群落多样性比较%Comparison of benthic macrofaunal communities in two mangrove habitats of Luoyangjiang Estuary in Quanzhou Bay

    Institute of Scientific and Technical Information of China (English)

    郭涛; 蔡立哲; 卓异; 饶义勇; 李想; 陈昕餠; 傅素晶; 纪剑锋


    In order to compare the benthic macrofaunal community in two mangrove habitats,Aegiceras corniculatum and Kandelia candel,in Luoyangjiang Estuary,Quanzhou Bay,China,benthic macrofauna was investigated in 4 sea-sons from April 201 1 to January 2012.A total of 49 benthic macrofaunal species were recorded,including 15 Annel-ida,8 Mollusca,15 Arthropoda,3 Chordata,2 Hexapod,1 Cnidaria,Platyhelminthes,Nemertea,Sipuncula,Oli-gochaeta and Bivalve.Nephtys oligobranchia,Assiminea brevicula,Uca arcuata,Actinia sp.showed high density in both two habitats,Phascolosoma esculenta is a dominant species in both two habitats but with lower density.Although the mean biomass of Kandelia candel was higher than Aegiceras corniculatum,the species number,density,diversity index(H′),evenness index(J)and richness index(d)of Aegiceras corniculatum were all higher.Two-way ANOVA showed that the diversity and evenness indexes of the two benthic macrofaunal communities had significant seasonal differences,habitat differences and habitat ×season differences.Cluster analysis showed high similarity between the benthic macrofaunal communities in two mangrove habitats because of same tidal zone and similar types of sediment and sediment particle size.%为探讨泉州湾洛阳江口桐花树和秋茄2种红树林生境的大型底栖动物群落是否存在明显差异,于2011年4月至2012年1月对2种红树林生境的大型底栖动物进行了季度定量调查.结果表明:4个季度在2种红树林生境定量取样获得大型底栖动物49种,其中多毛类15种,腹足类8种,甲壳类15种,鱼类3种,昆虫2种,刺胞动物、扁形动物、纽形动物、星虫动物、寡毛类和双壳类各1种.寡鳃齿吻沙蚕(Nephtys oligobranchia)、短拟沼螺(Assiminea brevicula)、弧边招潮蟹(Uca arcua-ta)、指海葵(Actinia sp.)等在2种生境均有较高的栖息密度,可口革囊星虫(Phascolosoma esculen-ta)是2种生境的常见种

  10. 文昌鱼SMYD家族基因的系统进化分析%Phylogenetic Analysis of the Amphioxus SMYD Gene Family

    Institute of Scientific and Technical Information of China (English)

    郭泉阳; 李红岩


    SMYD( SET and MYND domain containing,SMYD) are a class of proteins containing the SET func-tional domains. They play an important role in the regulation of chromosomal gene expression,cell cycle con-trol, cell division, differentiation and development. It is known that drosophila and vertebrates contain Smyd genes and scholars have done much research on the expression, function and evolution of these genes. Howev-er, research on the chordate SMYD family genes is limited. This article searched the cephalochordate amphioxus genome and found that amphioxus had six possible Smyd genes. Analysis of the functional domains of these Smyd genes showed that:amphioxus-related genes and those of other studied species,such as drosophi-la,xenopus,mouse,human are alike,all in different chromosomes. Analysis of gene structures shows that 3 Smyd genes of the amphioxus,2 of zebrafish and 4 of human have a SCOP functional domain in addition to the SET functional domains. Analysis of gene structure show that the genetic structure of vertebrates is conserva-tive,but invertebrates and chordata are less conservative. The results of phylogenetic analysis show that only two of the six amphioxus Smyd genes are high homologous with other species and the other four are relatively low. This paper aims to conduct a preliminary phylogenetic analysis of amphioxus SMYD family. What roles the Smyd genes in chordate amphioxus perform,and how they realize their functions still need further studies.%SMYD( SET and MYND domain containing,SMYD)是一类含有SET功能域的蛋白,在染色体的调节、基因的表达、细胞生长周期的控制、细胞的分裂、分化及发育等方面具有重要作用。目前已知在果蝇、脊椎动物中均含有Smyd基因,且这些基因的进化、表达及功能均有很多研究,但关于脊索动物SMYD家族基因的研究则很少。本文对头索动物文昌鱼的基因组进行搜索,发现文昌鱼有6个可能的Smyd基因。对Smyd基因在

  11. 布尼亚病毒及其引发的疾病%Bunyaviridae and Its Diseases

    Institute of Scientific and Technical Information of China (English)



    The bunyaviridae family comprises more than 300 viruses. Membership is usually based on antigenic interrelatedness or morphological similarity. Disease characterized by fever, headache, weakness, myalgia, pulmonary edema. The family is divided into 5 genera; 1. Orthobunyavirus: Bunyamwera, La Cross, Tahyna virus, transmitted mainly by mosquitoes. 2. Hantavirus; Hantaan virus, transmission does not require insects. 3. Nairovirus; Dugbe virus infection of cattle in West Africa, transmitted by ticks. 4. Phlebovirus;Sandfly fever, Rift valley fever, transmitted by sandflies. 5. Tospovirus; Tomato spotted wilt virus,only infect plant and non-vertebrate. Man is not known to be a natural or reservoir for any of these viruses. Virions are 80 ~ 120 nm in diameter, 5 ~ 10 nm projections visible on the surface. Genome consists of 3 pieces of negative stranded RNA. Virion has 2 surface glycoproteins Cl and C2, with HA and virus neutralization epitopes. Bunyaviridae is a family of negative stranded RNA viruses. Though generally found in arthropode or rodents, certain viruses in this family occasionally infect humans. Bunyaviridae are vector-borne viruses. With the exception of Hantaviruses transmission occurs via an arthropod vector. Hantaviruses are transmitted through contact with mice feces. Crimean-Congo hemorrhagic fever virus is associated with high levels of morbidity and mortality, consequently handling of these viruses most occurs with a biosafe level 4 laboratory. Hantavirus or Hantavirus hemorrhagic fever, common in China, Korea, Scandinavia, Russia, and the American southwest, is associated with high fever, lung edema and pulmonary failture. Mortality is around 55% of laboratory diagnosis of bunya virus infections. Virus isolation-intra-cranialinoculation of suckling mice is thought to be the most sensitive system available for virus isolation. However sensitive cell culture systems are available such as Vero, Vero E6, A549 and mosquito cells. Once isolated the

  12. Diretrizes para prevenção e tratamento da osteoporose induzida por glicocorticoide Guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis

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    Rosa Maria Rodrigues Pereira


    , Glucocorticoids/adverse effects, Prednisone/adverse effects, Dose-Response Relationship, Drug, Bone Density/drug effects, Bone Density Conservation Agents/pharmacological action, Osteoporosis/ prevention&control, Calcium, Vitamin D, Vitamin D deficiency, Calcitriol, Receptors, Calcitriol; 1-hydroxycholecalciferol, Hydroxycholecalciferols, 25-Hydroxyvitamin D3 1-alpha-hydroxylase OR Steroid Hydroxylases, Prevention and Control, Spinal fractures/prevention & control, Fractures, Spontaneous, Lumbar Vertebrae/injuries, Lifestyle, Alcohol Drinking, Smoking OR tobacco use disorder, Movement, Resistance Training, Exercise Therapy, Bone density OR Bone and Bones, Dual-Energy X-Ray Absorptiometry OR Absorptiometry Photon OR DXA, Densitometry, Radiography, (Diphosphonates Alendronate OR Risedronate Pamidronate OR propanolamines OR Ibandronate OR Zoledronic acid, Teriparatide OR PTH 1-34, Men AND premenopause, pregnancy, pregnancy outcome maternal, fetus, lactation, breast-feeding, teratogens, Children (6-12 anos, adolescence (13-18 anos. GRAU DE RECOMENDAÇÃO E FORÇA DE EVIDÊNCIA: A Estudos experimentais e observacionais de melhor consistência; B Estudos experimentais e observacionais de menor consistência; C Relatos de casos (estudos não controlados; D Opinião desprovida de avaliação crítica, com base em consensos, estudos fisiológicos ou modelos animais. OBJETIVO: Estabelecer as diretrizes para a prevenção e o tratamento da OPIG.Glucocorticoids (GC are used in almost all medical specialties, and approximately 0.5% of the general population of the United Kingdom receives those medications. With the increased survival of patients with rheumatological diseases, morbidity secondary to the use of those medications represents an important aspect of the management of our patients. The incidences of vertebral and non-vertebral fractures are elevated, ranging from 30% to 50% of the individuals on GC for over three months. Thus, osteoporosis and frailty fractures should be prevented