Sample records for human non-pigmented ciliary

  1. Effects of glaucoma medications and preservatives on cultured human trabecular meshwork and non-pigmented ciliary epithelial cell lines. (United States)

    Ammar, David A; Kahook, Malik Y


    We investigated the potential cytotoxicity of various topical ophthalmic glaucoma formulations containing different preservatives in cultured human trabecular meshwork (TM) and non-pigmented ciliary epithelial (NPCE) cell lines. We tested 0.004% travoprost preserved with either 0.015% benzalkonium chloride (BAK), sofZia or 0.001% Polyquad (PQ); and 0.005% latanoprost preserved with 0.020% BAK. We also tested a range of BAK concentrations in balanced salt solution (BSS). TM cells were treated for 10 min at 37°C with solutions diluted 1:10 to mimic the reduced penetration of topical preparations to the anterior chamber. Viability was determined by the uptake of the fluorescent vital dye calcein-AM (n = 6). BAK solutions (diluted 1:10) demonstrated a dose-dependent reduction in cell viability in both cell types (TM and NPCE). With a 1:10 dilution of 0.020% BAK, there were significantly more living NPCE cells (89 ± 6%) than TM cells (57 ± 6%; p < 0.001). In TM cells, travoprost + BAK had statistically fewer live cells (83 ± 5%) than both travoprost + sofZia (97 ± 5%) and travoprost + PQ (97 ± 6%; p < 0.05). Compared with BSS-treated NPCE cells, travoprost had statistically fewer live cells (p < 0.05) when preserved with BAK (85 ± 16%), sofZia (91 ± 6%) or PQ (94 ± 2%). These results demonstrate that substitution of BAK from topical ophthalmic drugs results in greater viability of cultured TM cells, the cells involved in the conventional outflow pathway. Cultured NPCE, responsible for aqueous inflow, appear more resilient to BAK.

  2. A feed-forward regulation of endothelin receptors by c-Jun in human non-pigmented ciliary epithelial cells and retinal ganglion cells.

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    Junming Wang

    Full Text Available c-Jun, c-Jun N-terminal kinase(JNK and endothelin B (ETB receptor have been shown to contribute to the pathogenesis of glaucoma. Previously, we reported that an increase of c-Jun and CCAAT/enhancer binding protein β (C/EBPβ immunohistostaining is associated with upregulation of the ETB receptor within the ganglion cell layer of rats with elevated intraocular pressure (IOP. In addition, both transcription factors regulate the expression of the ETB receptor in human non-pigmented ciliary epithelial cells (HNPE. The current study addressed the mechanisms by which ET-1 produced upregulation of ET receptors in primary rat retinal ganglion cells (RGCs and HNPE cells. Treatment of ET-1 and ET-3 increased the immunocytochemical staining of c-Jun and C/EBPβ in primary rat RGCs and co-localization of both transcription factors was observed. A marked increase in DNA binding activity of AP-1 and C/EBPβ as well as elevated protein levels of c-Jun and c-Jun-N-terminal kinase (JNK were detected following ET-1 treatment in HNPE cells. Overexpression of ETA or ETB receptor promoted the upregulation of c-Jun and also elevated its promoter activity. In addition, upregulation of C/EBPβ augmented DNA binding and mRNA expression of c-Jun, and furthermore, the interaction of c-Jun and C/EBPβ was confirmed using co-immunoprecipitation. Apoptosis of HNPE cells was identified following ET-1 treatment, and overexpression of the ETA or ETB receptor produced enhanced apoptosis. ET-1 mediated upregulation of c-Jun and C/EBPβ and their interaction may represent a novel mechanism contributing to the regulation of endothelin receptor expression. Reciprocally, c-Jun was also found to regulate the ET receptors and C/EBPβ appeared to play a regulatory role in promoting expression of c-Jun. Taken together, the data suggests that ET-1 triggers the upregulation of c-Jun through both ETA and ETB receptors, and conversely c-Jun also upregulates endothelin receptor expression

  3. Studies on bicarbonate transporters and carbonic anhydrase in porcine non-pigmented ciliary epithelium (United States)

    Shahidullah, Mohammad; C-H, To; Pelis, Ryan M.; Delamere, Nicholas A


    Purpose Bicarbonate transport plays a role in aqueous humor (AH) secretion. Here, we examined bicarbonate transport mechanisms and carbonic anhydrase (CA) in porcine non-pigmented ciliary epithelium (NPE). Methods Cytoplasmic pH (pHi) was measured in cultured porcine NPE loaded with BCECF. Anion exchanger (AE), sodium bicarbonate cotransporter (NBC) and CA were examined by RT-PCR and immunolocalization. AH secretion was measured in the intact porcine eye using a fluorescein dilution technique. Results Anion exchanger AE2, CAII and CAIV were abundant in the NPE layer. In cultured NPE superfused with a CO2/HCO3− free HEPES buffer, exposure to a CO2/HCO3−-containing buffer caused a rapid acidification followed by a gradual pHi increase. Subsequent removal of CO2/HCO3− with HEPES buffer caused rapid alkalinization followed by gradual pHi decrease. The rate of gradual alkalinization after addition of HCO3−/CO2 was inhibited by sodium-free conditions, DIDS, CA inhibitors acetazolamide and methazolamide but not by Na-H exchange inhibitor dimethylamiloride or low chloride buffer. The phase of gradual acidification after removal of HCO3−/CO2 was inhibited by DIDS, acetazolamide, methazolamide and by low chloride buffer. DIDS reduced baseline pHi. In the intact eye, DIDS and acetazolamide reduced AH secretion by 25% and 44% respectively. Conclusion The results suggest the NPE uses a Na+-HCO3− cotransporter to import bicarbonate and a Cl−/HCO3− exchanger to export bicarbonate. CA influences the rate of bicarbonate transport. AE2, CAII and CAIV are enriched in the NPE layer of the ciliary body and their coordinated function may contribute to AH secretion by effecting bicarbonate transport into the eye. PMID:19011010

  4. Gene Expression and Functional Annotation of the Human Ciliary Body Epithelia

    NARCIS (Netherlands)

    Janssen, Sarah F.; Gorgels, Theo G. M. F.; Bossers, Koen; ten Brink, Jacoline B.; Essing, Anke H. W.; Nagtegaal, Martijn; van der Spek, Peter J.; Jansonius, Nomdo M.; Bergen, Arthur A. B.


    Purpose: The ciliary body (CB) of the human eye consists of the non-pigmented (NPE) and pigmented (PE) neuro-epithelia. We investigated the gene expression of NPE and PE, to shed light on the molecular mechanisms underlying the most important functions of the CB. We also developed molecular

  5. Effect of cAMP on short-circuit current in isolated human ciliary body. (United States)

    Wu, Ren-yi; Ma, Ning; Hu, Qian-qian


    Cyclic adenosine monophosphate (cAMP) could activate chloride channels in bovine ciliary body and trigger an increase in the ionic current (short-circuit current, Isc) across the ciliary processes in pigs. The purpose of this study was to investigate how cAMP modulates Isc in isolated human ciliary processes and the possible involvement of chloride transport across the tissue in cAMP-induced Isc change. In an Ussing-type chamber system, the Isc changes induced by the cAMP analogue 8-bromo-cAMP and an adenylyl cyclase activator forskolin in isolated human ciliary processes were assessed. The involvement of Cl(-) component in the bath solution was investigated. The effect of Cl(-) channel (10 µmol/L niflumic acid and 1 mmol/L 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)), K(+) channel (10 mmol/L tetraethylammonium chloride (TEA)), or Na(+) channel blockers (1 mmol/L amiloride) on 8-bromo-cAMP-induced Isc change was also studied. Dose-dependently, 8-bromo-cAMP (10 nmol/L-30 µmol/L) or forskolin (10 nmol/L-3 µmol/L) increased Isc across the ciliary processes with an increase in negative potential difference on the non-pigmented epithelium (NPE) side of the tissue. Isc increase induced by 8-bromo-cAMP was more pronounced when the drug was applied on the NPE side than on the pigmented epithelium side. When the tissue was bathed in low Cl(-) solutions, the Isc increase was significantly inhibited. Finally, niflumic acid and DIDS, but not TEA or amiloride, significantly prevented the Isc increase induced by 8-bromo-cAMP. cAMP stimulates stroma-to-aqueous anionic transport in isolated human ciliary processes. Chloride is likely to be among the ions, the transportation of which across the tissue is triggered by cAMP, suggesting the potential role of cAMP in the process of aqueous humor formation in human eyes.

  6. Melatonin synthesis in the human ciliary body triggered by TRPV4 activation: Involvement of AANAT phosphorylation. (United States)

    Alkozi, Hanan Awad; Perez de Lara, María J; Pintor, Jesús


    Melatonin is a substance synthesized in the pineal gland as well as in other organs. This substance is involved in many ocular functions, giving its synthesis in numerous eye structures. Melatonin is synthesized from serotonin through two enzymes, the first limiting step into the synthesis of melatonin being aralkylamine N-acetyltransferase (AANAT). In this current study, AANAT phosphorylation after the activation of TRPV4 was studied using human non-pigmented epithelial ciliary body cells. Firstly, it was necessary to determine the adequate time and dose of the TRPV4 agonist GSK1016790A to reach the maximal phosphorylation of AANAT. An increase of 72% was observed after 5 min incubation with 10 nM GSK (**p melatonin synthesis. The involvement of a TRPV4 channel in melatonin synthesis was verified by antagonist and siRNA studies as a previous step to studying intracellular signalling. Studies performed on the second messengers involved in GSK induced AANAT phosphorylation were carried out by inhibiting several pathways. In conclusion, the activation of calmodulin and calmodulin-dependent protein kinase II was confirmed, as shown by the cascade seen in AANAT phosphorylation (***p melatonin levels. In conclusion, the activation of a TRPV4 present in human ciliary body epithelial cells produced an increase in AANAT phosphorylation and a further melatonin increase by a mechanism in which Ca-calmodulin and the calmodulin-dependent protein kinase II are involved. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. [Regeneration of the ciliary beat of human ciliated cells]. (United States)

    Wolf, G; Koidl, B; Pelzmann, B


    The influence of an isotonic, alkaline saline solution (diluted "Emser Sole" or brine from the spa of Bad Ems) on the ciliary beat of isolated cultured human ciliated cells of the upper respiratory tract was investigated. The ciliary beat was observed via an inverted phase contrast microscope (Zeiss Axiomat IDPC) and measured microphotometrically under physiological conditions and after the damaging influence of 1% propanal solution. Under physiological conditions the saline solution had a positive, although statistically not significant influence on the frequency of the ciliary beat. After damage of the cultivated cells by 1% propanal solution, the saline solution had a significant better influence on the regeneration of the cultured cells than a physiological sodium chloride solution. It is concluded that diluted brine from Bad Ems has a positive effect on the ciliary beat of the respiratory epithelium and accelerates its regeneration after damage by viral and bacterial infections, surgery or inhaled noxae.

  8. Gene expression and functional annotation of the human ciliary body epithelia.

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    Sarah F Janssen

    Full Text Available PURPOSE: The ciliary body (CB of the human eye consists of the non-pigmented (NPE and pigmented (PE neuro-epithelia. We investigated the gene expression of NPE and PE, to shed light on the molecular mechanisms underlying the most important functions of the CB. We also developed molecular signatures for the NPE and PE and studied possible new clues for glaucoma. METHODS: We isolated NPE and PE cells from seven healthy human donor eyes using laser dissection microscopy. Next, we performed RNA isolation, amplification, labeling and hybridization against 44×k Agilent microarrays. For microarray conformations, we used a literature study, RT-PCRs, and immunohistochemical stainings. We analyzed the gene expression data with R and with the knowledge database Ingenuity. RESULTS: The gene expression profiles and functional annotations of the NPE and PE were highly similar. We found that the most important functionalities of the NPE and PE were related to developmental processes, neural nature of the tissue, endocrine and metabolic signaling, and immunological functions. In total 1576 genes differed statistically significantly between NPE and PE. From these genes, at least 3 were cell-specific for the NPE and 143 for the PE. Finally, we observed high expression in the (NPE of 35 genes previously implicated in molecular mechanisms related to glaucoma. CONCLUSION: Our gene expression analysis suggested that the NPE and PE of the CB were quite similar. Nonetheless, cell-type specific differences were found. The molecular machineries of the human NPE and PE are involved in a range of neuro-endocrinological, developmental and immunological functions, and perhaps glaucoma.

  9. Effect of N-acetylcysteine on the human nasal ciliary activity in vitro

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    Stafanger, G; Bisgaard, H; Pedersen, M


    N-acetylcysteine (NAC) is widely used as a mucolytic agent, but the clinical and pharmacological effects of NAC are still unclear. It has recently been claimed in animal studies that NAC will stimulate ciliary beating frequency at low concentrations, while inhibiting beating at higher concentrati......N-acetylcysteine (NAC) is widely used as a mucolytic agent, but the clinical and pharmacological effects of NAC are still unclear. It has recently been claimed in animal studies that NAC will stimulate ciliary beating frequency at low concentrations, while inhibiting beating at higher...... concentrations. Using a microphoto-oscillographic method combined with microperfusion technique, we studied the direct effect of NAC on human nasal cilia. NAC caused a direct dose- and time-related decrease in ciliary beating frequency, which was detectable at 2 mg/ml and reached statistically significant levels...

  10. Safety assessment of thiolated polymers: effect on ciliary beat frequency in human nasal epithelial cells. (United States)

    Palmberger, Thomas F; Augustijns, Patrick; Vetter, Anja; Bernkop-Schnürch, Andreas


    The aim of this study was to investigate the nasal safety of gel formulations of thiolated polymers (thiomers) by assessing their effect on ciliary beat frequency (CBF) in human nasal epithelial cells. Poly(acrylic acid) 450 kDa-cysteine (PAA-cys) and alginate-cysteine (alg-cys) were synthesized by covalent attachment of L-cysteine to the polymeric backbone. The cationic polymer chitosan-thiobutylamidine (chito-TBA) was synthesized by attaching iminothiolane to chitosan. CBF using was measured by a photometric system. CBF was measured before incubating the cells with test gels, during incubation and after washing out the polymeric test gels to evaluate reversibility of cilio-inhibition. The influence of viscosity on CBF was determined by using hydroxyethylcellulose (HEC)-gels of various concentrations. Ciliary beating was observed to be affected by viscosity, but cilia were still beating in the presence of a HEC-gel displaying an apparent viscosity of 25 Pa.s. In case of thiolated polymers and their unmodified control, a concentration-dependent decrease in CBF could be observed. PAA-cys, alg-cys, chito-TBA and their corresponding unmodified controls exhibited a moderate cilio-inhibitory effect, followed by a partial recovery of CBF when used at a concentration of 1%. Alg-cys 2% and chito-TBA 2% (m/v) gels exhibited severe cilio-inhibition, which was partially reversible. L-cysteine and reduced glutathione led to mild cilio-inhibition at concentrations of 3% (m/v). Taking into account that dilution after application and cilio-modifying effects is usually more pronounced under in vitro conditions, thiomers can be considered as suitable excipients for nasal drug delivery systems.

  11. Influence of essential and fatty oils on ciliary beat frequency of human nasal epithelial cells. (United States)

    Neher, Andreas; Gstöttner, Michaela; Thaurer, Michael; Augustijns, Patrick; Reinelt, Monika; Schobersberger, Wolfgang


    In alternative and complementary medicine, the use of essential and fatty oils has become more and more popular. In addition to conventional medical therapies, self-medication is showing increasing popularity, using agents with unclear compounds and poorly controlled dosages. Among other disorders, these alternative treatments are used in bronchitis and rhinitis, including some topical applications. Thus, the influence on ciliated epithelia should be evaluated, because a disturbance of the ciliary function can lead to recurrent sinusitis and chronic rhinosinusitis. The aim of this study was to test the influence of fatty and essential oils on the ciliary beat frequency (CBF) of nasal mucosa in vivo. The influence of sesame oil, soy oil, peanut oil, Miglyol 840, thyme oil, lavender oil, eucalyptus oil, and menthol on the ciliary activity of nasal brushings was evaluated by digital high-speed imaging. The presence of most fatty oils resulted in an increase in CBF, the effect being highest for peanut oil. Miglyol 840 had no significant influence on CBF. The essential oils were tested at a concentration of 0.2 and 2%. Thyme oil did not affect CBF, whereas the presence of all other essentials oils resulted in an increase in CBF; the effect was higher at 0.2% than at 2%. Except thyme oil and Miglyol 840, all tested oils caused an increase in CBF. Interestingly, the 0.2% concentrations of essential oils resulted in stronger effects when compared with the 2% concentrations.

  12. Ciliary dysfunction and obesity. (United States)

    Mok, C A; Héon, E; Zhen, M


    Obesity associates with increased health risks such as heart disease, stroke and diabetes. The steady rise in the obese population worldwide poses an increasing burden on health systems. Genetic factors contribute to the development of obesity, and the elucidation of their physiological functions helps to understand the cause, and improve the prevention, diagnosis and treatment for this disorder. Primary cilia are evolutionarily conserved organelles whose dysfunctions lead to human disorders now defined as ciliopathies. Human ciliopathies present pleiotropic and overlapping phenotypes that often include retinal degeneration, cystic renal anomalies and obesity. Increasing evidence implicates an intriguing involvement of cilia in lipid/energy homeostasis. Here we discuss recent studies in support of the key roles of ciliary genes in the development and pathology of obesity in various animal models. Genes affecting ciliary development and function may pose promising candidate underlying genetic factors that contribute to the development of common obesity.

  13. Pathogenesis of Congenital Rubella Virus Infection in Human Fetuses: Viral Infection in the Ciliary Body Could Play an Important Role in Cataractogenesis

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    Thong Van Nguyen


    Interpretation: Our study based on the pathological examination demonstrated that the rubella virus infection occurred via systemic organs of human fetuses. This fact was confirmed by immunohistochemistry and direct detection of viral RNA in multiple organs. To the best of our knowledge, this study is the first report demonstrating that the rubella virus infection occurred via systemic organs of the human body. Importantly, virus infection of the ciliary body could play an important role in cataractogenesis.

  14. Pseudotumor of Ciliary Body

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    Mary Varghese


    Full Text Available Orbital pseudotumor is a benign disease involving the orbital structures. Pseudotumor of the ciliary body is rare. We present a case of a 27-year-old male who presented with gradual visual loss, pain, and redness in his left eye. On examination he was found to have a yellowish white mass at the periphery of anterior chamber in his left eye and ultrasound biomicroscopy (UBM revealed a ciliary body mass in the same eye. He was treated with systemic steroids, which was tapered over a period of 8 weeks. His symptoms improved and the ciliary body mass disappeared with no recurrence over the next 6 months. UBM is an important diagnostic tool for diagnosing ciliary body mass. Early diagnosis and prompt treatment with systemic steroids may help resolve pseudotumor of the ciliary body.

  15. Deficiency in nucleotide excision repair family gene activity, especially ERCC3, is associated with non-pigmented hair fiber growth.

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    Mei Yu

    Full Text Available We conducted a microarray study to discover gene expression patterns associated with a lack of melanogenesis in non-pigmented hair follicles (HF by microarray. Pigmented and non-pigmented HFs were collected and micro-dissected into the hair bulb (HB and the upper hair sheaths (HS including the bulge region. In comparison to pigmented HS and HBs, nucleotide excision repair (NER family genes ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, ERCC6, XPA, NTPBP, HCNP, DDB2 and POLH exhibited statistically significantly lower expression in non- pigmented HS and HBs. Quantitative PCR verified microarray data and identified ERCC3 as highly differentially expressed. Immunohistochemistry confirmed ERCC3 expression in HF melanocytes. A reduction in ERCC3 by siRNA interference in human melanocytes in vitro reduced their tyrosinase production ability. Our results suggest that loss of NER gene function is associated with a loss of melanin production capacity. This may be due to reduced gene transcription and/or reduced DNA repair in melanocytes which may eventually lead to cell death. These results provide novel information with regard to melanogenesis and its regulation.

  16. Ozone Sensitivity and Catalase Activity in Pigmented and Non-Pigmented Strains of Serratia Marcescens. (United States)

    de Ondarza, José


    Ozone exposure rapidly leads to bacterial death, making ozone an effective disinfectant in food industry and health care arena. However, microbial defenses may moderate this effect and play a role in the effective use of oxidizing agents for disinfection. Serratia marcescens is an opportunistic pathogen, expressing genes differentially during infection of a human host. A better understanding of regulatory systems that control expression of Serratia 's virulence genes and defenses is therefore valuable. Here, we investigated the role of pigmentation and catalase in Serratia marcescens on survival to ozone exposure. Pigmented and non-pigmented strains of Serratia marcescens were cultured to exponential or stationary phase and exposed to 5 ppm of gaseous ozone for 2.5 - 10 minutes. Survival was calculated via plate counts. Catalase activity was measured photometrically and tolerance to hydrogen peroxide was assayed by disk-diffusion. Exposure of S. marcescens to 5 ppm gaseous ozone kills > 90% of cells within 10 minutes in a time and concentration-dependent manner. Although pigmented Serratia (grown at 28°C) survived ozonation better than unpigmented Serratia (grown at 35°C), non-pigmented mutant strains of Serratia had similar ozone survival rates, catalase activity and H 2 O 2 tolerance as wild type strains. Rather, ozone survival and catalase activity were elevated in 6 hour cultures compared to 48 hour cultures. Our studies did not bear out a role for prodigiosin in ozone survival. Rather, induction of oxidative stress responses during exponential growth increased both catalase activity and ozone survival in both pigmented and unpigmented S. marcescens .

  17. Genetic and Virulent Difference Between Pigmented and Non-pigmented Staphylococcus aureus


    Jing Zhang; Yujuan Suo; Daofeng Zhang; Fangning Jin; Hang Zhao; Chunlei Shi


    Staphyloxanthin (STX), a golden carotenoid pigment produced by Staphylococcus aureus, is suggested to act as an important virulence factor due to its antioxidant properties. Restraining biosynthesis of STX was considered as an indicator of virulence decline in pigmented S. aureus isolates. However, it is not clear whether natural non-pigmented S. aureus isolates have less virulence than pigmented ones. In this study, it is aimed to compare the pigmented and non-pigmented S. aureus isolates to...

  18. Genetic and Virulent Difference Between Pigmented and Non-pigmented Staphylococcus aureus. (United States)

    Zhang, Jing; Suo, Yujuan; Zhang, Daofeng; Jin, Fangning; Zhao, Hang; Shi, Chunlei


    Staphyloxanthin (STX), a golden carotenoid pigment produced by Staphylococcus aureus , is suggested to act as an important virulence factor due to its antioxidant properties. Restraining biosynthesis of STX was considered as an indicator of virulence decline in pigmented S. aureus isolates. However, it is not clear whether natural non-pigmented S. aureus isolates have less virulence than pigmented ones. In this study, it is aimed to compare the pigmented and non-pigmented S. aureus isolates to clarify the genetic and virulent differences between the two groups. Here, 132 S. aureus isolates were divided into two phenotype groups depending on the absorbance (OD 450 ) of the extracted carotenoids. Then, all isolates were subjected to spa typing and multilocus sequence typing (MLST), and then the detection of presence of 30 virulence factors and the gene integrity of crtN and crtM . Furthermore, 24 typical S. aureus isolates and 4 S. argenteus strains were selected for the murine infection assay of in vivo virulence, in which the histological observation and enumeration of CFUs were carried out. These isolates were distributed in 26 sequence types (STs) and 49 spa types. The pigmented isolates were scattered in 25 STs, while the non-pigmented isolates were more centralized, which mainly belonged to ST20 (59%) and ST25 (13%). Among the 54 non-pigmented isolates, about 20% carried intact crtN and crtM genes. The in vivo assay suggested that comparing with pigmented S. aureus , non-pigmented S. aureus and S. argenteus strains did not show a reduced virulence in murine sepsis models. Therefore, it suggested that there were no significant genetic and virulent differences between pigmented and non-pigmented S. aureus .

  19. Genetic and Virulent Difference Between Pigmented and Non-pigmented Staphylococcus aureus

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    Jing Zhang


    Full Text Available Staphyloxanthin (STX, a golden carotenoid pigment produced by Staphylococcus aureus, is suggested to act as an important virulence factor due to its antioxidant properties. Restraining biosynthesis of STX was considered as an indicator of virulence decline in pigmented S. aureus isolates. However, it is not clear whether natural non-pigmented S. aureus isolates have less virulence than pigmented ones. In this study, it is aimed to compare the pigmented and non-pigmented S. aureus isolates to clarify the genetic and virulent differences between the two groups. Here, 132 S. aureus isolates were divided into two phenotype groups depending on the absorbance (OD450 of the extracted carotenoids. Then, all isolates were subjected to spa typing and multilocus sequence typing (MLST, and then the detection of presence of 30 virulence factors and the gene integrity of crtN and crtM. Furthermore, 24 typical S. aureus isolates and 4 S. argenteus strains were selected for the murine infection assay of in vivo virulence, in which the histological observation and enumeration of CFUs were carried out. These isolates were distributed in 26 sequence types (STs and 49 spa types. The pigmented isolates were scattered in 25 STs, while the non-pigmented isolates were more centralized, which mainly belonged to ST20 (59% and ST25 (13%. Among the 54 non-pigmented isolates, about 20% carried intact crtN and crtM genes. The in vivo assay suggested that comparing with pigmented S. aureus, non-pigmented S. aureus and S. argenteus strains did not show a reduced virulence in murine sepsis models. Therefore, it suggested that there were no significant genetic and virulent differences between pigmented and non-pigmented S. aureus.

  20. Photoreceptor Sensory Cilium: Traversing the Ciliary Gate

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    Hemant Khanna


    Full Text Available Cilia are antenna-like extensions of the plasma membrane found in nearly all cell types. In the retina of the eye, photoreceptors develop unique sensory cilia. Not much was known about the mechanisms underlying the formation and function of photoreceptor cilia, largely because of technical limitations and the specific structural and functional modifications that cannot be modeled in vitro. With recent advances in microscopy techniques and molecular and biochemical approaches, we are now beginning to understand the molecular basis of photoreceptor ciliary architecture, ciliary function and its involvement in human diseases. Here, I will discuss the studies that have revealed new knowledge of how photoreceptor cilia regulate their identity and function while coping with high metabolic and trafficking demands associated with processing light signal.

  1. Mutations in ZMYND10, a gene essential for proper axonemal assembly of inner and outer dynein arms in humans and flies, cause primary ciliary dyskinesia

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    Moore, Daniel J; Onoufriadis, Alexandros; Shoemark, Amelia


    Primary ciliary dyskinesia (PCD) is a ciliopathy characterized by airway disease, infertility, and laterality defects, often caused by dual loss of the inner dynein arms (IDAs) and outer dynein arms (ODAs), which power cilia and flagella beating. Using whole-exome and candidate-gene Sanger resequ...

  2. CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs

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    Merveille, Anne-Christine; Davis, Erica E; Becker-Heck, Anita


    Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory c...

  3. Cellular Mechanisms of Ciliary Length Control

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    Jacob Keeling


    Full Text Available Cilia and flagella are evolutionarily conserved, membrane-bound, microtubule-based organelles on the surface of most eukaryotic cells. They play important roles in coordinating a variety of signaling pathways during growth, development, cell mobility, and tissue homeostasis. Defects in ciliary structure or function are associated with multiple human disorders called ciliopathies. These diseases affect diverse tissues, including, but not limited to the eyes, kidneys, brain, and lungs. Many processes must be coordinated simultaneously in order to initiate ciliogenesis. These include cell cycle, vesicular trafficking, and axonemal extension. Centrioles play a central role in both cell cycle progression and ciliogenesis, making the transition between basal bodies and mitotic spindle organizers integral to both processes. The maturation of centrioles involves a functional shift from cell division toward cilium nucleation which takes place concurrently with its migration and fusion to the plasma membrane. Several proteinaceous structures of the distal appendages in mother centrioles are required for this docking process. Ciliary assembly and maintenance requires a precise balance between two indispensable processes; so called assembly and disassembly. The interplay between them determines the length of the resulting cilia. These processes require a highly conserved transport system to provide the necessary substances at the tips of the cilia and to recycle ciliary turnover products to the base using a based microtubule intraflagellar transport (IFT system. In this review; we discuss the stages of ciliogenesis as well as mechanisms controlling the lengths of assembled cilia.

  4. UV-B affects the immune system and promotes nuclear abnormalities in pigmented and non-pigmented bullfrog tadpoles. (United States)

    Franco-Belussi, Lilian; Fanali, Lara Zácari; De Oliveira, Classius


    Ultra-Violet (UV) radiation is a stressor of the immune system and causes DNA damage. Leukocytes can change in response to environmental changes in anurans, making them an important biomarker of stressful situations. The initial barrier against UV in ectothermic animals is melanin-containing cells in skin and in their internal organs. Here, we tested the effects of UV exposure on immune cells and DNA integrity in pigmented and non-pigmented tadpoles of Lithobates catesbeianus. We used an inflammation model with lipopolysaccharide (LPS) of Escherichia coli to test synergic effects of UV and LPS. We tested the following hypotheses: 1) DNA damage caused by UV will be more pronounced in non-pigmented than in pigmented animals; 2) LPS increases leukocytes in both pigmented and non-pigmented animals by systemic inflammation; 3) The combined LPS and UV exposure will decrease the number of leukocytes. We found that the frequency of immune cells differed between pigmented and non-pigmented tadpoles. UV exposure increased mast cells and DNA damage in erythrocytes in both pigmented and non-pigmented tadpoles, while leukocytes decreased after UV exposure. Non-pigmented tadpoles experienced DNA damage and a lower lymphocyte count earlier than pigmented tadpoles. UV altered immune cells likely as a consequence of local and systemic inflammation. These alterations were less severe in pigmented than in non-pigmented animals. UV and LPS increased internal melanin in pigmented tadpoles, which were correlated with DNA damage and leukocytes. Here, we described for the first time the effects of UV and LPS in immune cells of pigmented and non-pigmented tadpoles. In addition, we demonstrated that internal melanin in tadpoles help in these defenses, since leukocyte responses were faster in non-pigmented animals, supporting the hypothesis that melanin is involved in the initial innate immune response. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Genetics Home Reference: primary ciliary dyskinesia (United States)

    ... primary ciliary dyskinesia also have year-round nasal congestion and a chronic cough. Chronic respiratory tract infections ... likely due to abnormal cilia in the fallopian tubes. Another feature of primary ciliary dyskinesia is recurrent ...

  6. Novel Bioconjugation Strategy Using Elevated Hydrostatic Pressure: A Case Study for the Site-Specific Attachment of Polyethylene Glycol (PEGylation) of Recombinant Human Ciliary Neurotrophic Factor. (United States)

    Wang, Qi; Zhang, Chun; Guo, Fangxia; Li, Zenglan; Liu, Yongdong; Su, Zhiguo


    In this paper, we reported a novel strategy for the site-specific attachment of polyethylene glycol (PEGylation) of proteins using elevated hydrostatic pressure. The process was similar to the conventional one except the reactor was under elevated hydrostatic pressure. The model protein was recombinant human ciliary neurotrophic factor (rhCNTF), and the reagent was monomethoxy-polyethylene glycol-maleimide (mPEG-MAL). PEGylation with mPEG (40 kDa)-MAL at pH 7.0 under normal pressure for 5 h achieved a less than 5% yield. In comparison, when the pressure was elevated, the PEGylation yield was increased dramatically, reaching nearly 90% at 250 MPa. Furthermore, the following phenomena were observed: (1) high-hydrostatic-pressure PEGylation (HHPP) could operate at a low reactant ratio of 1:1.2 (rhCNTF to mPEG-MAL), while the conventional process needs a much-higher ratio. (2) Short and long chains of PEG gave a similar yield of 90% in HHPP, while the conventional yield for the short chain of the PEG was higher than that of the long chain. (3) The reaction pH in the range of 7.0 to 8.0 had almost no influence upon the yield of HHPP, while the PEGylation yield was significantly increased by a factor of three from pH 7.0 to 8.0 at normal pressure. Surface accessibility analysis was performed using GRASP2 software, and we found that Cys17 of rhCNTF was located at the concave patches, which may have steric hindrance for the PEG to approach. The speculated benefit of HHPP was the facilitation of target-site exposure, reducing the steric hindrance and making the reaction much easier. Structure and activity analysis demonstrated that the HHPP product was comparable to the PEGylated rhCNTF prepared through a conventional method. Overall, this work demonstrated that HHPP, as we proposed, may have application potentials in various conjugations of biomacromolecules.

  7. Cell context-specific expression of primary cilia in the human testis and ciliary coordination of Hedgehog signalling in mouse Leydig cells

    DEFF Research Database (Denmark)

    Berg Nygaard, Marie; Almstrup, Kristian; Lindbæk, Louise


    Primary cilia are sensory organelles that coordinate numerous cellular signalling pathways during development and adulthood. Defects in ciliary assembly or function lead to a series of developmental disorders and diseases commonly referred to as ciliopathies. Still, little is known about...... cells of mature seminiferous epithelium, but present in Sertoli cell-only tubules in Klinefelter syndrome testis. Peritubular cells in atrophic testis produce overly long cilia. Furthermore cultures of growth-arrested immature mouse Leydig cells express primary cilia that are enriched in components...

  8. CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms (United States)

    Panizzi, Jennifer R.; Becker-Heck, Anita; Castleman, Victoria H.; Al-Mutairi, Dalal; Liu, Yan; Loges, Niki T.; Pathak, Narendra; Austin-Tse, Christina; Sheridan, Eamonn; Schmidts, Miriam; Olbrich, Heike; Werner, Claudius; Häffner, Karsten; Hellman, Nathan; Chodhari, Rahul; Gupta, Amar; Kramer-Zucker, Albrecht; Olale, Felix; Burdine, Rebecca D.; Schier, Alexander F.; O’Callaghan, Christopher; Chung, Eddie MK; Reinhardt, Richard; Mitchison, Hannah M.; King, Stephen M.; Omran, Heymut; Drummond, Iain A.


    Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation, and to establish laterality1. Cilia motility defects cause Primary Ciliary Dyskinesia (PCD, MIM 242650), a disorder affecting 1:15-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive cilia bending2. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD linked loci3. Here we show that the zebrafish cilia paralysis mutant schmalhanstn222 (smh) mutant encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a regulated gene. Screening 146 unrelated PCD families identified patients in six families with reduced outer dynein arms, carrying mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103 functions as a tightly bound, axoneme-associated protein. The results identify Ccdc103 as a novel dynein arm attachment factor that when mutated causes Primary Ciliary Dyskinesia. PMID:22581229


    International Nuclear Information System (INIS)



    In the present investigation, five mutant strains from A. alternate were isolated after exposure to gamma irradiation at dose level 8 kGy. The mutant isolated strains (MIS) were non-producing dark pigment and producing polysaccharide. The mutant isolated strain (MIS) belong to the Alternaria alternata MIS (1-5). In shake flask experiments, the exopolysaccharide (EPS) production was 2.90-5.24 g/l and biomass 5.8-8.31g/l. The effect of some fermentation conditions on grape wastes by A. alternata were investigated to produce EPS using gamma irradiation and non-pigment strain. The economical optimum fermentation condition for the highest EPS production by MIS4 when grown on grape waste containing 150 g/l sugar, incubation temperature 28 o C, pH 7 with addition of both 2 % yeast extract and 1.5 % surfactant triton x-100 achieved 14.68 g/l EPS and 6.22 g/l biomass

  10. Primary ciliary dyskinesia: clinical and genetic aspects

    Directory of Open Access Journals (Sweden)

    E. D’Auria


    Full Text Available Primary ciliary dyskinesia (PCD is a rare, genetically heterogeneous disease, characterized by ciliary disfunction and impaired mucociliary clearance, resulting in a range of clinical manifestations such as chronic bronchitis, bronchiectasis, chronic rhino-sinusitis, chronic otitis media, situs viscerum inversus in almost 40-50% of cases and male infertility. The triad situs viscerum inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. Up to now little is known about genetic, diagnostic and therapeutic aspects of primary motile ciliary diseases in children: for this reason, diagnosis is generally delayed and almost all treatments for PCD are not based on randomized studies but extrapolated from cystic fibrosis guidelines. The aim of this review is to propose to pediatricians a summary of current clinical and diagnostic evidence to obtain better knoledwge of this condition. The earlier diagnosis and the right treatment are both crucial to improve the prognosis of PCD.

  11. Arf4 is required for Mammalian development but dispensable for ciliary assembly.

    Directory of Open Access Journals (Sweden)

    John A Follit


    Full Text Available The primary cilium is a sensory organelle, defects in which cause a wide range of human diseases including retinal degeneration, polycystic kidney disease and birth defects. The sensory functions of cilia require specific receptors to be targeted to the ciliary subdomain of the plasma membrane. Arf4 has been proposed to sort cargo destined for the cilium at the Golgi complex and deemed a key regulator of ciliary protein trafficking. In this work, we show that Arf4 binds to the ciliary targeting sequence (CTS of fibrocystin. Knockdown of Arf4 indicates that it is not absolutely required for trafficking of the fibrocystin CTS to cilia as steady-state CTS levels are unaffected. However, we did observe a delay in delivery of newly synthesized CTS from the Golgi complex to the cilium when Arf4 was reduced. Arf4 mutant mice are embryonic lethal and die at mid-gestation shortly after node formation. Nodal cilia appeared normal and functioned properly to break left-right symmetry in Arf4 mutant embryos. At this stage of development Arf4 expression is highest in the visceral endoderm but we did not detect cilia on these cells. In the visceral endoderm, the lack of Arf4 caused defects in cell structure and apical protein localization. This work suggests that while Arf4 is not required for ciliary assembly, it is important for the efficient transport of fibrocystin to cilia, and also plays critical roles in non-ciliary processes.

  12. Cyanide levels found in infected cystic fibrosis sputum inhibit airway ciliary function. (United States)

    Nair, Chandrika; Shoemark, Amelia; Chan, Mario; Ollosson, Sarah; Dixon, Mellissa; Hogg, Claire; Alton, Eric W F W; Davies, Jane C; Williams, Huw D


    We have previously reported cyanide at concentrations of up to 150 μM in the sputum of cystic fibrosis patients infected with Pseudomonas aeruginosa and a negative correlation with lung function. Our aim was to investigate possible mechanisms for this association, focusing on the effect of pathophysiologically relevant cyanide levels on human respiratory cell function. Ciliary beat frequency measurements were performed on nasal brushings and nasal air-liquid interface (ALI) cultures obtained from healthy volunteers and cystic fibrosis patients. Potassium cyanide decreased ciliary beat frequency in healthy nasal brushings (n = 6) after 60 min (150 μM: 47% fall, pcyanide as a key component inhibiting the ciliary beat frequency. If cyanide production similarly impairs mucocilliary clearance in vivo, it could explain the link with increased disease severity observed in cystic fibrosis patients with detectable cyanide in their airway. ©ERS 2014.

  13. Ciliary body melanoma with optic nerve invasion. (United States)

    al-Haddab, S; Hidayat, A; Tabbara, K F


    A case of melanoma of the ciliary body is presented. Initially the patient was diagnosed and treated for uveitis, but following CT scanning and ultrasound a tumour was detected and the eye enucleated. Histopathologically it was found that the tumour had invaded the optic nerve head, apparently via Cloquet's canal. Images PMID:2310725

  14. Phenolic acids, anthocyanins, proanthocyanidins, antioxidant activity, minerals and their correlations in non-pigmented, red, and black rice. (United States)

    Shao, Yafang; Hu, Zhanqiang; Yu, Yonghong; Mou, Renxiang; Zhu, Zhiwei; Beta, Trust


    Soluble-free, soluble-conjugated, insoluble-bound phenolics and antioxidant activity, flavonoid (TFC), proanthocyanidins (TPAC), anthocyanins and minerals of fifteen whole rice grains with different colors were investigated. Soluble-free protocatechuic and vanillic acids were only quantified in black rice, which had the most quantities. Non-pigmented rice had no detectable conjugated protocatechuic and 2,5-dihydroxybenzoic acids both of which were found in black and red rice, respectively. The main bound phenolic acids were ferulic and p-coumaric, as well as 2,5-dihydroxybenzoic in red rice and protocatechuic and vanillic acids in black rice. Soluble-conjugated phenolics, TFC, and anthocyanins were negatively correlated with L ∗ , b ∗ , C and H° values. TPAC was positively correlated with a ∗ (Pblack rice groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Ciliary neurotrophic factor is an endogenous pyrogen.


    Shapiro, L; Zhang, X X; Rupp, R G; Wolff, S M; Dinarello, C A


    Fever is initiated by the action of polypeptide cytokines called endogenous pyrogens, which are produced by the host during inflammation, trauma, or infection and which elevate the thermoregulatory set point in the hypothalamus. Ciliary neurotrophic factor (CNTF) supports the differentiation and survival of central and peripheral neurons. We describe the activity of CNTF as intrinsically pyrogenic in the rabbit. CNTF induced a monophasic fever which rose rapidly (within the first 12 min) foll...

  16. Bug22 influences cilium morphology and the post-translational modification of ciliary microtubules

    Directory of Open Access Journals (Sweden)

    Teresa Mendes Maia


    Cilia and flagella are organelles essential for motility and sensing of environmental stimuli. Depending on the cell type, cilia acquire a defined set of functions and, accordingly, are built with an appropriate length and molecular composition. Several ciliary proteins display a high degree of conservation throughout evolution and mutations in ciliary genes are associated with various diseases such as ciliopathies and infertility. Here, we describe the role of the highly conserved ciliary protein, Bug22, in Drosophila. Previous studies in unicellular organisms have shown that Bug22 is required for proper cilia function, but its exact role in ciliogenesis has not been investigated yet. Null Bug22 mutant flies display cilia-associated phenotypes and nervous system defects. Furthermore, sperm differentiation is blocked at the individualization stage, due to impaired migration of the individualization machinery. Tubulin post-translational modifications (PTMs such as polyglycylation, polyglutamylation or acetylation, are determinants of microtubule (MT functions and stability in centrioles, cilia and neurons. We found defects in the timely incorporation of polyglycylation in sperm axonemal MTs of Bug22 mutants. In addition, we found that depletion of human Bug22 in RPE1 cells resulted in the appearance of longer cilia and reduced axonemal polyglutamylation. Our work identifies Bug22 as a protein that plays a conserved role in the regulation of PTMs of the ciliary axoneme.

  17. Long-term outcome of Tunisian children with primary ciliary ...

    African Journals Online (AJOL)

    Background: Primary ciliary dyskinesia (PCD) is rare. Its diagnosis requires experienced specialists and expensive infrastructure. Its prognosis is variable. Objective: To study the long-term outcome of PCD in Tunisian children with ciliary ultra-structure defects detected by electron microscope. Methods: Covering a period of ...

  18. The Pediatric Choroidal and Ciliary Body Melanoma Study

    DEFF Research Database (Denmark)

    Al-Jamal, Rana'a T; Cassoux, Nathalie; Desjardins, Laurence


    PURPOSE: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18...

  19. Enzymatic processing of pigmented and non pigmented rice bran on changes in oryzanol, polyphenols and antioxidant activity. (United States)

    Prabhu, Ashish A; Jayadeep, A


    Bran from different rice varieties is a treasure of nutrients and nutraceuticals, and its use is limited due to the poor sensory and functional properties. Application of enzymes can alter the functional and phytochemical properties. So the effect of endo-xylanase, cellulase and their combination on microstructural, nutraceutical and antioxidant properties of pigmented (Jyothi) and non-pigmented (IR64) rice bran were investigated. Scanning electron micrograph revealed micro structural changes in fibre structures on processing. All the enzymatic processing methods resulted in an increase in the content of oryzanol, soluble, bound and total polyphenols, flavonoid and tannin. It also showed an increase in the bioactivity with respect to free radical scavenging activity and total antioxidant activity. However, extent of the increase in bio-actives varied with the type of bran and enzyme application method. Endo-xylanase showed higher percentage difference compared to controls of Jyothi and IR64 bran extracts respectively in the content of the bound (10 & 19 %) and total (20 & 14 %) polyphenols. Combination of both the enzymes resulted in higher percentage increase of bioactive components and properties. It resulted in greater percentage difference compared to controls of Jyothi and IR64 extracts respectively in the content of soluble (58 & 17 %) and total (21 & 14 %) polyphenols, flavonoids (12 & 38 %), γ-oryzanol (10 & 12 %), free radical scavenging activity (64 & 30 %) and total antioxidant activity (82 & 136 %). It may be concluded that enzymatic bio-processing of bran with cellulose and hemicellulose degrading enzymes can improve its nutraceutical properties, and it may be used for development of functional foods.

  20. An international registry for primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Werner, Claudius; Lablans, Martin; Ataian, Maximilian


    Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder leading to chronic upper and lower airway disease. Fundamental data on epidemiology, clinical presentation, course and treatment strategies are lacking in PCD. We have established an international PCD registry to realise...... an unmet need for an international platform to systematically collect data on incidence, clinical presentation, treatment and disease course.The registry was launched in January 2014. We used internet technology to ensure easy online access using a web browser under Data from 201...... methods in addition to classical clinical symptoms. Preliminary analysis of lung function data demonstrated a mean annual decline of percentage predicted forced expiratory volume in 1 s of 0.59% (95% CI 0.98-0.22).Here, we present the development of an international PCD registry as a new promising tool...

  1. Species variation in biology and physiology of the ciliary epithelium: similarities and differences. (United States)

    Do, Chi Wai; Civan, Mortimer M


    Glaucoma is a leading cause of irreversible blindness worldwide. Lowering intraocular pressure (IOP) is the only strategy documented to delay the appearance and retard the progression of vision loss. One major approach for lowering IOP is to slow the rate of aqueous humor formation by the ciliary epithelium. As discussed in the present review, the transport basis for this secretion is largely understood. However, several substantive issues are yet to be resolved, including the integrated regulation of secretion, the functional topography of the ciliary epithelium, and the degree and significance of species variation in aqueous humor inflow. This review discusses species differences in net secretion, particularly of Cl(-) and HCO(3)(-) secretion. Identifying animal models most accurately mimicking aqueous humor formation in the human will facilitate development of future novel initiatives to lower IOP.

  2. Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival. (United States)

    Omori, Yoshihiro; Chaya, Taro; Katoh, Kimiko; Kajimura, Naoko; Sato, Shigeru; Muraoka, Koichiro; Ueno, Shinji; Koyasu, Toshiyuki; Kondo, Mineo; Furukawa, Takahisa


    Cilia function as cell sensors in many organs, and their disorders are referred to as "ciliopathies." Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors.

  3. LRRC6 mutation causes primary ciliary dyskinesia with dynein arm defects.

    Directory of Open Access Journals (Sweden)

    Amjad Horani

    Full Text Available Despite recent progress in defining the ciliome, the genetic basis for many cases of primary ciliary dyskinesia (PCD remains elusive. We evaluated five children from two unrelated, consanguineous Palestinian families who had PCD with typical clinical features, reduced nasal nitric oxide concentrations, and absent dynein arms. Linkage analyses revealed a single common homozygous region on chromosome 8 and one candidate was conserved in organisms with motile cilia. Sequencing revealed a single novel mutation in LRRC6 (Leucine-rich repeat containing protein 6 that fit the model of autosomal recessive genetic transmission, leading to a change of a highly conserved amino acid from aspartic acid to histidine (Asp146His. LRRC6 was localized to the cytoplasm and was up-regulated during ciliogenesis in human airway epithelial cells in a Foxj1-dependent fashion. Nasal epithelial cells isolated from affected individuals and shRNA-mediated silencing in human airway epithelial cells, showed reduced LRRC6 expression, absent dynein arms, and slowed cilia beat frequency. Dynein arm proteins were either absent or mislocalized to the cytoplasm in airway epithelial cells from a primary ciliary dyskinesia subject. These findings suggest that LRRC6 plays a role in dynein arm assembly or trafficking and when mutated leads to primary ciliary dyskinesia with laterality defects.

  4. HEATR2 plays a conserved role in assembly of the ciliary motile apparatus.

    Directory of Open Access Journals (Sweden)

    Christine P Diggle


    Full Text Available Cilia are highly conserved microtubule-based structures that perform a variety of sensory and motility functions during development and adult homeostasis. In humans, defects specifically affecting motile cilia lead to chronic airway infections, infertility and laterality defects in the genetically heterogeneous disorder Primary Ciliary Dyskinesia (PCD. Using the comparatively simple Drosophila system, in which mechanosensory neurons possess modified motile cilia, we employed a recently elucidated cilia transcriptional RFX-FOX code to identify novel PCD candidate genes. Here, we report characterization of CG31320/HEATR2, which plays a conserved critical role in forming the axonemal dynein arms required for ciliary motility in both flies and humans. Inner and outer arm dyneins are absent from axonemes of CG31320 mutant flies and from PCD individuals with a novel splice-acceptor HEATR2 mutation. Functional conservation of closely arranged RFX-FOX binding sites upstream of HEATR2 orthologues may drive higher cytoplasmic expression of HEATR2 during early motile ciliogenesis. Immunoprecipitation reveals HEATR2 interacts with DNAI2, but not HSP70 or HSP90, distinguishing it from the client/chaperone functions described for other cytoplasmic proteins required for dynein arm assembly such as DNAAF1-4. These data implicate CG31320/HEATR2 in a growing intracellular pre-assembly and transport network that is necessary to deliver functional dynein machinery to the ciliary compartment for integration into the motile axoneme.

  5. Primary ciliary dyskinesia: a report from ATS 2001, May 18–23, San Francisco

    Directory of Open Access Journals (Sweden)

    Noone Peadar G


    Full Text Available Abstract Primary ciliary dyskinesia (PCD is a genetic disorder of abnormal ciliary structure and function that leads to defective mucociliary clearance, resulting in oto-sino-pulmonary disease, and infertility. The disease is currently under intense investigation by a number of research groups worldwide. At the recent American Thoracic Society meeting in San Francisco in May 2001, two sessions focused on PCD; a symposium session on May 21 with several featured expert speakers was followed by a mini-symposium on Tuesday May 22, with one featured speaker and presentation of nine abstracts covering a range of research topics. Mattias Salathe (University of Miami, USA and Stephen Brody (Washington University, St Louis, USA chaired the symposium session. Presentations focused on the clinical spectrum of PCD, the genetics of PCD, a proteomics approach to detail the structure of cilia, the role of cilia in the embryology of situs laterality, and airway epithelial cell biology. The mini-symposium was chaired by Peadar Noone (University of North Carolina, USA and Malcolm King (University of Alberta, USA and included presentations on the use of PCD as a human disease model, accurate definition of the phenotype using clinical and cell biologic markers, and molecular studies. The latter reports ranged from isolation of a protein involved in ciliary structure and function to genetic studies using linkage analysis and the candidate gene approach. Clinicians and scientists alike displayed considerable interest at both sessions, and there were several lively question–answer sessions.

  6. Paramecium swimming and ciliary beating patterns: a study on four RNA interference mutations. (United States)

    Funfak, Anette; Fisch, Cathy; Abdel Motaal, Hatem T; Diener, Julien; Combettes, Laurent; Baroud, Charles N; Dupuis-Williams, Pascale


    Paramecium cells swim and feed by beating their thousands of cilia in coordinated patterns. The organization of these patterns and its relationship with cell motility has been the subject of a large body of work, particularly as a model for ciliary beating in human organs where similar organization is seen. However the rapid motion of the cells makes quantitative measurements very challenging. Here we provide detailed measurements of the swimming of Paramecium cells from high-speed video at high magnification, as they move in microfluidic channels. An image analysis protocol allows us to decouple the cell movement from the motion of the cilia, thus allowing us to measure the ciliary beat frequency (CBF) and the spatio-temporal organization into metachronal waves along the cell periphery. Two distinct values of the CBF appear at different regions of the cell: most of the cilia beat in the range of 15 to 45 Hz, while the cilia in the peristomal region beat at almost double the frequency. The body and peristomal CBF display a nearly linear relation with the swimming velocity. Moreover the measurements do not display a measurable correlation between the swimming velocity and the metachronal wave velocity on the cell periphery. These measurements are repeated for four RNAi silenced mutants, where proteins specific to the cilia or to their connection to the cell base are depleted. We find that the mutants whose ciliary structure is affected display similar swimming to the control cells albeit with a reduced efficiency, while the mutations that affect the cilia's anchoring to the cell lead to strongly reduced ability to swim. This reduction in motility can be related to a loss of coordination between the ciliary beating in different parts of the cell.

  7. Regulation of protein phosphorylation of the intermediate-sized filament vimentin in the ciliary epithelium of the mammalian eye

    International Nuclear Information System (INIS)

    Coca-Prados, M.


    The intermediate-sized filaments of vimentin-type (Mr = 57,000) have been identified biochemically and immunochemically as a major cytoskeleton component in the ciliary epithelium of the mammalian eye. When human or rabbit ciliary processes, or cultured ciliary epithelial-derived cells were incubated in serum-free medium containing [ 32 P]orthophosphate and any of the following agents: 1) beta-adrenergic agonists (isoproterenol or epinephrine), 2) direct activators of adenylate cyclase (cholera toxin or forskolin), 3) analogs of cyclic AMP (8-Br-cAMP), or 4) prostaglandin E1, the phosphorylation of vimentin was significantly enhanced. The maximal enhancement ranged, in vivo and in vitro, from about 3-fold in human to 5-fold in rabbit, with either 1 mM 8-Br-cAMP or 0.1 microM forskolin. Indirect immunofluorescence microscopy using a monoclonal antibody, anti-vimentin, allowed the localization of vimentin filaments in cultured ciliary epithelial cells. Treatment of these cells in culture with the catecholamine hormone, isoproterenol (1 microM), resulted in a profound reorganization of vimentin filaments. This may be correlated with the enhanced levels of phosphorylated vimentin observed upon increasing cellular cyclic AMP

  8. Ciliary and non-ciliary expression and function of PACRG during vertebrate development

    Directory of Open Access Journals (Sweden)

    Thumberger Thomas


    Full Text Available Abstract Background Park2-co-regulated gene (PACRG is evolutionarily highly conserved from green algae to mammals. In Chlamydomonas and trypanosomes, the PACRG protein associates with flagella. Loss of PACRG results in shortened or absent flagella. In mouse the PACRG protein is required for spermatogenesis. The purpose of the present study was to analyze (1 the expression patterns of PACRG during vertebrate embryogenesis, and (2 whether the PACRG protein was required for left-right (LR axis specification through cilia-driven leftward flow in Xenopus laevis. Methods PACRG cDNAs were cloned and expression was analyzed during early embryonic development of Xenopus, mouse, rabbit and zebrafish. Antisense morpholino oligonucleotide (MO mediated gene knockdown was applied in Xenopus to investigate LR development at the level of tissue morphology, leftward flow and asymmetric marker gene expression, using timelapse videography, scanning electron microscopy (SEM and whole-mount in situ hybridization. Results were statistically evaluated using Wilcoxon paired and χ2 tests. Results PACRG mRNA expression was found in cells and tissues harboring cilia throughout the vertebrates. Highly localized expression was also detected in the brain. During early development, PACRG was specifically localized to epithelia where leftward flow arises, that is, the gastrocoel roof plate (GRP in Xenopus, the posterior notochord (PNC in mammals and Kupffer’s vesicle (KV in zebrafish. Besides its association with ciliary axonemes, subcellular localization of PACRG protein was found around the nucleus and in a spotty pattern in the cytoplasm. A green fluorescent protein (GFP fusion construct preferentially labeled cilia, rendering PACRG a versatile marker for live imaging. Loss-of-function in the frog resulted dose dependently in LR, neural tube closure and gastrulation defects, representing ciliary and non-ciliary functions of PACRG. Conclusions The PACRG protein is a novel

  9. Ciliary neurotrophic factor is an endogenous pyrogen. (United States)

    Shapiro, L; Zhang, X X; Rupp, R G; Wolff, S M; Dinarello, C A


    Fever is initiated by the action of polypeptide cytokines called endogenous pyrogens, which are produced by the host during inflammation, trauma, or infection and which elevate the thermoregulatory set point in the hypothalamus. Ciliary neurotrophic factor (CNTF) supports the differentiation and survival of central and peripheral neurons. We describe the activity of CNTF as intrinsically pyrogenic in the rabbit. CNTF induced a monophasic fever which rose rapidly (within the first 12 min) following intravenous injection; CNTF fever was blocked by pretreatment with indomethacin. The fever induced by CNTF was not due to contaminating endotoxins. Increasing doses of CNTF resulted in prolongation of the fever, suggesting the subsequent induction of additional endogenous pyrogenic activity. After passive transfer of plasma obtained during CNTF-induced fever, endogenous pyrogen activity was not present in the circulation; CNTF also did not induce the endogenous pyrogens interleukin 1, tumor necrosis factor, or interleukin 6 in vitro. Nevertheless, a second endogenous pyrogen may originate within the central nervous system following the systemic injection of CNTF. Of the four endogenous pyrogens described to date (interleukin 1, tumor necrosis factor, interferon, and interleukin 6), CNTF, like interleukin 6, utilizes the cell-surface gp 130 signal-transduction apparatus.

  10. Bio-inspired ciliary force sensor for robotic platforms

    KAUST Repository

    Ribeiro, Pedro


    The detection of small forces is of great interest in any robotic application that involves interaction with the environment (e.g., objects manipulation, physical human-robot interaction, minimally invasive surgery), since it allows the robot to detect the contacts early on and to act accordingly. In this letter, we present a sensor design inspired by the ciliary structure frequently found in nature, consisting of an array of permanently magnetized cylinders (cilia) patterned over a giant magnetoresistance sensor (GMR). When these cylinders are deformed in shape due to applied forces, the stray magnetic field variation will change the GMR sensor resistivity, thus enabling the electrical measurement of the applied force. In this letter, we present two 3 mm × 3 mm prototypes composed of an array of five cilia with 1 mm of height and 120 and 200 μm of diameter for each prototype. A minimum force of 333 μN was measured. A simulation model for determining the magnetized cylinders average stray magnetic field is also presented.

  11. Bio-inspired ciliary force sensor for robotic platforms

    KAUST Repository

    Ribeiro, Pedro; Khan, Mohammed Asadullah; Alfadhel, Ahmed; Kosel, Jü rgen; Franco, Fernando; Cardoso, Susana; Bernardino, Alexandre; Schmitz, Alexander; Santos-Victor, Jose; Jamone, Lorenzo


    The detection of small forces is of great interest in any robotic application that involves interaction with the environment (e.g., objects manipulation, physical human-robot interaction, minimally invasive surgery), since it allows the robot to detect the contacts early on and to act accordingly. In this letter, we present a sensor design inspired by the ciliary structure frequently found in nature, consisting of an array of permanently magnetized cylinders (cilia) patterned over a giant magnetoresistance sensor (GMR). When these cylinders are deformed in shape due to applied forces, the stray magnetic field variation will change the GMR sensor resistivity, thus enabling the electrical measurement of the applied force. In this letter, we present two 3 mm × 3 mm prototypes composed of an array of five cilia with 1 mm of height and 120 and 200 μm of diameter for each prototype. A minimum force of 333 μN was measured. A simulation model for determining the magnetized cylinders average stray magnetic field is also presented.

  12. Bug22p, a Conserved Centrosomal/Ciliary Protein Also Present in Higher Plants, Is Required for an Effective Ciliary Stroke in Paramecium ▿ † (United States)

    Laligné, C.; Klotz, C.; Garreau de Loubresse, N.; Lemullois, M.; Hori, M.; Laurent, F. X.; Papon, J. F.; Louis, B.; Cohen, J.; Koll, F.


    Centrioles, cilia, and flagella are ancestral conserved organelles of eukaryotic cells. Among the proteins identified in the proteomics of ciliary proteins in Paramecium, we focus here on a protein, Bug22p, previously detected by cilia and basal-body high-throughput studies but never analyzed per se. Remarkably, this protein is also present in plants, which lack centrioles and cilia. Bug22p sequence alignments revealed consensus positions that distinguish species with centrioles/cilia from plants. In Paramecium, antibody and green fluorescent protein (GFP) fusion labeling localized Bug22p in basal bodies and cilia, and electron microscopy immunolabeling refined the localization to the terminal plate of the basal bodies, the transition zone, and spots along the axoneme, preferentially between the membrane and the microtubules. RNA interference (RNAi) depletion of Bug22p provoked a strong decrease in swimming speed, followed by cell death after a few days. High-speed video microscopy and morphological analysis of Bug22p-depleted cells showed that the protein plays an important role in the efficiency of ciliary movement by participating in the stroke shape and rigidity of cilia. The defects in cell swimming and growth provoked by RNAi can be complemented by expression of human Bug22p. This is the first reported case of complementation by a human gene in a ciliate. PMID:20118210

  13. Bug22p, a conserved centrosomal/ciliary protein also present in higher plants, is required for an effective ciliary stroke in Paramecium. (United States)

    Laligné, C; Klotz, C; de Loubresse, N Garreau; Lemullois, M; Hori, M; Laurent, F X; Papon, J F; Louis, B; Cohen, J; Koll, F


    Centrioles, cilia, and flagella are ancestral conserved organelles of eukaryotic cells. Among the proteins identified in the proteomics of ciliary proteins in Paramecium, we focus here on a protein, Bug22p, previously detected by cilia and basal-body high-throughput studies but never analyzed per se. Remarkably, this protein is also present in plants, which lack centrioles and cilia. Bug22p sequence alignments revealed consensus positions that distinguish species with centrioles/cilia from plants. In Paramecium, antibody and green fluorescent protein (GFP) fusion labeling localized Bug22p in basal bodies and cilia, and electron microscopy immunolabeling refined the localization to the terminal plate of the basal bodies, the transition zone, and spots along the axoneme, preferentially between the membrane and the microtubules. RNA interference (RNAi) depletion of Bug22p provoked a strong decrease in swimming speed, followed by cell death after a few days. High-speed video microscopy and morphological analysis of Bug22p-depleted cells showed that the protein plays an important role in the efficiency of ciliary movement by participating in the stroke shape and rigidity of cilia. The defects in cell swimming and growth provoked by RNAi can be complemented by expression of human Bug22p. This is the first reported case of complementation by a human gene in a ciliate.

  14. A systematic correlation analysis of carotenoids, chlorophyll, non-pigmented cell mass, and cell number for the blueprint of Dunaliella salina culture in a photobioreactor. (United States)

    Song, Hyeon Gi; Byeon, Seon Yeong; Chung, Goo Yong; Jung, Sang-Myung; Choi, Jung Il; Shin, Hwa Sung


    Microalgal carotenoids are attractive health ingredients, but their production should be optimized to improve cost-effectiveness. Understanding cellular physiology centered on carotenoid synthesis is the prerequisite for this work. Therefore, systematic correlation analyses were conducted among chlorophyll, carotenoids, non-pigmented cell mass, and cell number of Dunaliella salina in a specified condition over a relatively long culture time. First, an integrated correlation was performed: a temporal profile of the carotenoids was correlated with those of other factors, including chlorophyll, non-pigmented cell mass, and cell number. Pearson and Spearman correlation analyses were performed to identify linearity and monotonicity of the correlation, respectively, and then cross-correlation was executed to determine if the correlation had a time lag. Second, to understand the cellular potential of metabolism, the procedure was repeated to provide a data set composed of the specific synthesis rates of the factors or growth rate, which additionally provided kinetic correlations among the constituting components of the cell, excluding the effect of cell number. This systematic approach could generate a blueprint model that is composed of only what it needs, which could make it possible to efficiently control and optimize the process.

  15. Progressive hemifacial atrophy with ciliary body atrophy and ocular hypotony

    Directory of Open Access Journals (Sweden)

    T Ashwini Kini


    Full Text Available Progressive hemifacial atrophy (PHA is a disease of unknown etiology affecting one-half of the face. Ocular involvement is uncommon. Atrophy of iris is rare, with only a few cases of partial atrophy being reported in the literature. We report a case of total atrophy of iris and ciliary body with associated ocular hypotony in a 16-year-old girl with PHA. We believe this is the first reported case of complete atrophy of iris and ciliary body in PHA. Ocular hypotony in PHA was thought to be due to intra-ocular inflammation. However in our case it appears to be secondary to severe atrophy of the ciliary body.

  16. Clinical care of children with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Lucas, Jane S; Alanin, Mikkel Christian; Collins, Samuel


    INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare heterogeneous disorder, usually inherited as an autosomal recessive condition but X-linked inheritance is also described. Abnormal ciliary function in childhood leads to neonatal respiratory distress in term infants, persistent wet cough...... is inappropriate since differences in pathophysiology, morbidity and prognosis risk treatment failure and lack of adherence. Areas covered: Review authors searched PubMed and Cochrane databases for publications relating to management of children with PCD. Because of the paucity of data, we emphasise the need...

  17. hemingway is required for sperm flagella assembly and ciliary motility in Drosophila. (United States)

    Soulavie, Fabien; Piepenbrock, David; Thomas, Joëlle; Vieillard, Jennifer; Duteyrat, Jean-Luc; Cortier, Elisabeth; Laurençon, Anne; Göpfert, Martin C; Durand, Bénédicte


    Cilia play major functions in physiology and development, and ciliary dysfunctions are responsible for several diseases in humans called ciliopathies. Cilia motility is required for cell and fluid propulsion in organisms. In humans, cilia motility deficiencies lead to primary ciliary dyskinesia, with upper-airways recurrent infections, left-right asymmetry perturbations, and fertility defects. In Drosophila, we identified hemingway (hmw) as a novel component required for motile cilia function. hmw encodes a 604-amino acid protein characterized by a highly conserved coiled-coil domain also found in the human orthologue, KIAA1430. We show that HMW is conserved in species with motile cilia and that, in Drosophila, hmw is expressed in ciliated sensory neurons and spermatozoa. We created hmw-knockout flies and found that they are hearing impaired and male sterile. hmw is implicated in the motility of ciliated auditory sensory neurons and, in the testis, is required for elongation and maintenance of sperm flagella. Because HMW is absent from mature flagella, we propose that HMW is not a structural component of the motile axoneme but is required for proper acquisition of motile properties. This identifies HMW as a novel, evolutionarily conserved component necessary for motile cilium function and flagella assembly.

  18. Long-term outcome of Tunisian children with primary ciliary ...

    African Journals Online (AJOL)

    Objective: To study the long-term outcome of PCD in Tunisian children with ciliary ultra-structure defects detected by electron .... The middle lobe was as much affected as the right up- .... distress syndrome (ARDS) after one and four years of.

  19. Effect of air pollutants on ciliary activity of respiratory tract

    Energy Technology Data Exchange (ETDEWEB)

    Omachi, S; Kita, H


    The effect of sulfur dioxide, nitrogen dioxide, nitric oxide, ozone, and formaldehyde on the ciliary activity of an excised specimen of the trachea of a guinea pig was investigated. The influence of these gases is determined by the Half Reduction Time of the ciliary activity, which is the time lapse from the beginning of the gas exposure at a certain concentration to the point of which the activity is reduced by half. The Half Reduction Time of the ciliary activity by each gas at the concentration of 50 ppM is SO/sub 2/, 4 min; HCHO, 5 min; NO/sub 2/, 10 min; NO, 14 min; and O/sub 3/, 20 min. The influence of the easily water soluble gases such as SO/sub 2/ and HCHO on the ciliary activity is severe compared with the less water soluble ones, NO/sub 2/ and O/sub 3/, which pass over the mucous surface of the upper airway without dissolving to the mucous layer.

  20. Multicavitary ciliary body melanoma presenting as a cyst

    Directory of Open Access Journals (Sweden)

    Jennifer Jang


    Full Text Available Cyst-like cavities in uveal melanoma occur rarely and can simulate a benign intraocular cystic lesion resulting in delayed diagnosis and inappropriate management. Herein, we describe a 66-year-old Caucasian female who presented with a "cystic" ciliary body mass in the right eye oculus dexter (OD. Slit lamp examination OD showed anterior bulging of the iris temporally from an underlying pigmented ciliary body mass and transillumination disclosed slight shadow from the tumor. Ultrasound biomicroscopy (UBM revealed multiple cyst-like cavities within a tumor, lined by "thick walls" of at least 200 μm and occupying 80% of the tumor volume. A clinical diagnosis of multi-cavitary ciliary body melanoma was suspected and partial lamellar sclero iridocyclectomy was performed. Histopathology confirmed the diagnosis of low-grade spindle melanoma of the ciliary body with multiple empty and fluid filled cyst-like cavities without epithelial lining. UBM is an important diagnostic tool in the differentiation of "thick walled" cavitary melanoma from "thin walled" benign pigment epithelial cyst.

  1. Flagellar Synchronization Is a Simple Alternative to Cell Cycle Synchronization for Ciliary and Flagellar Studies. (United States)

    Dutta, Soumita; Avasthi, Prachee


    The unicellular green alga Chlamydomonas reinhardtii is an ideal model organism for studies of ciliary function and assembly. In assays for biological and biochemical effects of various factors on flagellar structure and function, synchronous culture is advantageous for minimizing variability. Here, we have characterized a method in which 100% synchronization is achieved with respect to flagellar length but not with respect to the cell cycle. The method requires inducing flagellar regeneration by amputation of the entire cell population and limiting regeneration time. This results in a maximally homogeneous distribution of flagellar lengths at 3 h postamputation. We found that time-limiting new protein synthesis during flagellar synchronization limits variability in the unassembled pool of limiting flagellar protein and variability in flagellar length without affecting the range of cell volumes. We also found that long- and short-flagella mutants that regenerate normally require longer and shorter synchronization times, respectively. By minimizing flagellar length variability using a simple method requiring only hours and no changes in media, flagellar synchronization facilitates the detection of small changes in flagellar length resulting from both chemical and genetic perturbations in Chlamydomonas . This method increases our ability to probe the basic biology of ciliary size regulation and related disease etiologies. IMPORTANCE Cilia and flagella are highly conserved antenna-like organelles that found in nearly all mammalian cell types. They perform sensory and motile functions contributing to numerous physiological and developmental processes. Defects in their assembly and function are implicated in a wide range of human diseases ranging from retinal degeneration to cancer. Chlamydomonas reinhardtii is an algal model system for studying mammalian cilium formation and function. Here, we report a simple synchronization method that allows detection of small

  2. Congenital adenoma of the iris and ciliary body: light and electron microscopic observations.


    Rennie, I G; Parsons, M A; Palmer, C A


    A 23-year-old man had a lesion in the right inferior iris which appeared to have enlarged since it was first seen when the patient was aged 5 years. The lesion was excised by a partial iridocyclectomy. Histopathologically the neoplasm was composed of both pigmented and non-pigmented cells. Pseudoacini, containing acid mucopolysaccharides, were present throughout the tumour matrix. Electron microscopically the non-pigmented cells were found to possess a convoluted plasmalemma, abundant rough e...

  3. Effects of perfluorooctane sulfonate on tracheal ciliary beating frequency in mice

    International Nuclear Information System (INIS)

    Matsubara, Eriko; Nakahari, Takashi; Yoshida, Hideyo; Kuroiwa, Toshihiko; Harada, Kouji H.; Inoue, Kayoko; Koizumi, Akio


    Perfluorooctane sulfonate (PFOS) is one of the emerging persistent organic pollutants, ubiquitously found in the global environment, even in human serum. PFOS has been reported to perturb Ca 2+ homeostasis in Paramecium, cardiomyocytes and neurons. Since ciliary beat frequency (CBF) in the trachea is known to be increased by cytoplasmic Ca 2+ elevation, the effects of PFOS on CBF were evaluated in a slice preparation using video-enhanced contrast microscopy. PFOS increased CBF by 11% (P 2+ concentration ([Ca 2+ ] i ) in mouse tracheal ciliary cells. In Ca 2+ -free solution, PFOS at 100 μM failed to increase CBF (0.96-fold of vehicle control). The addition of Gd 3+ (1 μM), a store-operated Ca 2+ channel blocker, did not prevent the increase in CBF (1.09-fold (P + concentration (50 mM), which causes depolarization of the plasma membrane potential and a transient increase in [Ca 2+ ] i , increased CBF by 20% (P 2+ channels (VDCCs) in stimulation of CBF. Nifedipine (30 μM), a selective VDCC blocker, antagonized the effects of high K + (0.92-fold of high K + solution) and PFOS (0.96-fold of vehicle control) on CBF. In cells from peroxisome proliferator-activated receptor α (PPARα)-null mice, PFOS still increased CBF (1.12-fold (P 2+ through VDCC

  4. Intraflagellar Transport (IFT) Role in Ciliary Assembly, Resorption and Signalling

    DEFF Research Database (Denmark)

    Pedersen, Lotte B; Rosenbaum, Joel L


    Cilia and flagella have attracted tremendous attention in recent years as research demonstrated crucial roles for these organelles in coordinating a number of physiologically and developmentally important signaling pathways, including the platelet-derived growth factor receptor (PDGFR) alpha, Sonic...... hedgehog, polycystin, and Wnt pathways. In addition, the realization that defective assembly or function of cilia can cause a plethora of diseases and developmental defects ("ciliopathies") has increased focus on the mechanisms by which these antenna-like, microtubular structures assemble. Ciliogenesis...... mechanisms and functions of IFT. In addition to a general, up-to-date description of IFT, we discuss mechanisms by which proteins are selectively targeted to the ciliary compartment, with special focus on the ciliary transition zone. Finally, we briefly review the role of IFT in cilia-mediated signaling...

  5. Melanocytoma of the ciliary body misdiagnosed as iridodialysis

    Directory of Open Access Journals (Sweden)

    Kim M


    Full Text Available Moosang Kim, Seung-Jun LeeDepartment of Ophthalmology, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaAbstract: A 62-year-old female presented to our institution with dimness of vision in her right eye. On examination, her best corrected visual acuity was 20/100 in the right eye. The intraocular pressures were 14 mmHg in both eyes. Slit-lamp examination revealed nuclear sclerotic cataracts bilaterally and iridodialysis in her right eye. Seven days after the first visit, cataract surgery was performed without any complications. One year later, she presented to our institution with acute visual loss and ocular pain in the right eye. Best corrected visual acuity of the right eye was light perception and the intraocular pressure was 44 mmHg. Slit-lamp examination revealed a ciliary body mass with widespread pigment dispersion in the anterior segment. Due to no useful vision and uncontrolled pain, enucleation of the right eye was performed. Histopathologic examination revealed a melanocytoma of the ciliary body.Keywords: ciliary body, iridodialysis, melanocytoma

  6. Culture of primary ciliary dyskinesia epithelial cells at air-liquid interface can alter ciliary phenotype but remains a robust and informative diagnostic aid.

    Directory of Open Access Journals (Sweden)

    Robert A Hirst

    Full Text Available The diagnosis of primary ciliary dyskinesia (PCD requires the analysis of ciliary function and ultrastructure. Diagnosis can be complicated by secondary effects on cilia such as damage during sampling, local inflammation or recent infection. To differentiate primary from secondary abnormalities, re-analysis of cilia following culture and re-differentiation of epithelial cells at an air-liquid interface (ALI aids the diagnosis of PCD. However changes in ciliary beat pattern of cilia following epithelial cell culture has previously been described, which has brought the robustness of this method into question. This is the first systematic study to evaluate ALI culture as an aid to diagnosis of PCD in the light of these concerns.We retrospectively studied changes associated with ALI-culture in 158 subjects referred for diagnostic testing at two PCD centres. Ciliated nasal epithelium (PCD n = 54; non-PCD n  111 was analysed by high-speed digital video microscopy and transmission electron microscopy before and after culture.Ciliary function was abnormal before and after culture in all subjects with PCD; 21 PCD subjects had a combination of static and uncoordinated twitching cilia, which became completely static following culture, a further 9 demonstrated a decreased ciliary beat frequency after culture. In subjects without PCD, secondary ciliary dyskinesia was reduced.The change to ciliary phenotype in PCD samples following cell culture does not affect the diagnosis, and in certain cases can assist the ability to identify PCD cilia.

  7. Value of transmission electron microscopy for primary ciliary dyskinesia diagnosis in the era of molecular medicine: Genetic defects with normal and non-diagnostic ciliary ultrastructure. (United States)

    Shapiro, Adam J; Leigh, Margaret W


    Primary ciliary dyskinesia (PCD) is a genetic disorder causing chronic oto-sino-pulmonary disease. No single diagnostic test will detect all PCD cases. Transmission electron microscopy (TEM) of respiratory cilia was previously considered the gold standard diagnostic test for PCD, but 30% of all PCD cases have either normal ciliary ultrastructure or subtle changes which are non-diagnostic. These cases are identified through alternate diagnostic tests, including nasal nitric oxide measurement, high-speed videomicroscopy analysis, immunofluorescent staining of axonemal proteins, and/or mutation analysis of various PCD causing genes. Autosomal recessive mutations in DNAH11 and HYDIN produce normal TEM ciliary ultrastructure, while mutations in genes encoding for radial spoke head proteins result in some cross-sections with non-diagnostic alterations in the central apparatus interspersed with normal ciliary cross-sections. Mutations in nexin link and dynein regulatory complex genes lead to a collection of different ciliary ultrastructures; mutations in CCDC65, CCDC164, and GAS8 produce normal ciliary ultrastructure, while mutations in CCDC39 and CCDC40 cause absent inner dynein arms and microtubule disorganization in some ciliary cross-sections. Mutations in CCNO and MCIDAS cause near complete absence of respiratory cilia due to defects in generation of multiple cellular basal bodies; however, the scant cilia generated may have normal ultrastructure. Lastly, a syndromic form of PCD with retinal degeneration results in normal ciliary ultrastructure through mutations in the RPGR gene. Clinicians must be aware of these genetic causes of PCD resulting in non-diagnostic TEM ciliary ultrastructure and refrain from using TEM of respiratory cilia as a test to rule out PCD.

  8. Localization of multidrug resistance-associated protein 2 in the nonpigmented ciliary epithelium of the eye. (United States)

    Pelis, Ryan M; Shahidullah, Mohammad; Ghosh, Sikha; Coca-Prados, Miguel; Wright, Stephen H; Delamere, Nicholas A


    The nonpigmented epithelium (NPE) of the ciliary body represents an important component of the blood-aqueous barrier of the eye. Many therapeutic drugs penetrate poorly across the NPE into the aqueous humor of the eye interior. Several of these therapeutic drugs, such as methotrexate, vincristine, and etoposide, are substrates of the multidrug resistance-associated protein 2 (MRP2). Abundant MRP2 protein was detected by Western blot in homogenates of human ciliary body and freshly dissected porcine NPE. In cultured porcine NPE, the intracellular accumulation of the MRP2 substrates calcein (1.8-fold), 5-(and-6)-carboxy-2',7'-dichlorofluorescein (22.1-fold), and doxorubicin (1.9-fold) was significantly increased in the presence of 50 microM MK571 ((E)-3-[[[3-[2-(7-chloro-2-quinolinyl)-ethenyl]phenyl]-[[3-dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid), an MRP inhibitor. In addition, the intracellular accumulation of the MRP2 substrate glutathione methylfluorescein was increased by 50 microM MK571 (4.3-fold), 500 microM indomethacin (2.6-fold), and 50 microM cyclosporin A (2.1-fold) but not by 500 microM sulfinpyrazone. These data are consistent with MRP2-mediated transport activity in cultured NPE, and MRP2 mRNA (reverse transcriptase-polymerase chain reaction) and protein (Western blot) were detected in the cultured cells. Immunolocalization studies in native human and porcine eyes showed MRP2 protein at the apical interface of the NPE and pigmented cell layers. Close examination of MRP2 immunoreactivity supported the conclusion that MRP2 is localized in the apical membrane of the NPE. MRP2 at the apical membrane of NPE cells may be involved in protecting intraocular tissues from exposure to potentially harmful toxins.

  9. Ventilation inhomogeneity in children with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Green, Kent; Buchvald, Frederik F; Marthin, June Kehlet


    The lung clearance index (LCI) derived from the multiple breath inert gas washout (MBW) test reflects global ventilation distribution inhomogeneity. It is more sensitive than forced expiratory volume in 1 s (FEV(1)) for detecting abnormal airway function and correlates closely with structural lung...... damage in children with cystic fibrosis, which shares features with primary ciliary dyskinesia (PCD). Normalised phase III slope indices S(cond) and S(acin) reflect function of the small conducting and acinar airways, respectively. The involvement of the peripheral airways assessed by MBW tests has...

  10. An autocrine ATP release mechanism regulates basal ciliary activity in airway epithelium. (United States)

    Droguett, Karla; Rios, Mariana; Carreño, Daniela V; Navarrete, Camilo; Fuentes, Christian; Villalón, Manuel; Barrera, Nelson P


    Extracellular ATP, in association with [Ca 2+ ] i regulation, is required to maintain basal ciliary beat frequency. Increasing extracellular ATP levels increases ciliary beating in airway epithelial cells, maintaining a sustained response by inducing the release of additional ATP. Extracellular ATP levels in the millimolar range, previously associated with pathophysiological conditions of the airway epithelium, produce a transient arrest of ciliary activity. The regulation of ciliary beat frequency is dependent on ATP release by hemichannels (connexin/pannexin) and P2X receptor activation, the blockage of which may even stop ciliary movement. The force exerted by cilia, measured by atomic force microscopy, is reduced following extracellular ATP hydrolysis. This result complements the current understanding of the ciliary beating regulatory mechanism, with special relevance to inflammatory diseases of the airway epithelium that affect mucociliary clearance. Extracellular nucleotides, including ATP, are locally released by the airway epithelium and stimulate ciliary activity in a [Ca 2+ ] i -dependent manner after mechanical stimulation of ciliated cells. However, it is unclear whether the ATP released is involved in regulating basal ciliary activity and mediating changes in ciliary activity in response to chemical stimulation. In the present study, we evaluated ciliary beat frequency (CBF) and ciliary beating forces in primary cultures from mouse tracheal epithelium, using videomicroscopy and atomic force microscopy (AFM), respectively. Extracellular ATP levels and [Ca 2+ ] i were measured by luminometric and fluorimetric assays, respectively. Uptake of ethidium bromide was measured to evaluate hemichannel functionality. We show that hydrolysis of constitutive extracellular ATP levels with apyrase (50 U ml -1 ) reduced basal CBF by 45% and ciliary force by 67%. The apyrase effect on CBF was potentiated by carbenoxolone, a hemichannel inhibitor, and oxidized ATP, an

  11. Oligodendroglioma of the ciliary body: a unique case report and the review of literature

    International Nuclear Information System (INIS)

    Guo, Qing; Hao, Jie; Sun, Shou bin; Xu, Shou ping; Yang, Qian; Guo, Qi liang; Cui, Guo dong


    To date, there is no report in the international literature of an oligodendroglioma of the ciliary body, nor is there an analysis of the possible origins of this lesion. Here we report on a 52-year-old man admitted to our hospital with a ciliary body tumor revealed by clinical examination and ultrasound, computed tomography and magnetic resonance imaging studies. Following enucleation, pathological and immunohistochemical analyses were performed. Postoperative histopathological staining results included OLIGO-2(+) and GFAP(-), leading to a pathological diagnosis of oligodendroglioma of the ciliary body in the right eye (WHO grade II). Since malignant gliomas derive from transformed neural stem cells, the presence of oligodendroglioma in the ciliary body supports the hypothesis that gliomas can occur wherever neural stem cells exist. Tumors of the ciliary body derived from oligodendrocytes are difficult to diagnose; pathological analyses are essential

  12. Automatic analysis of ciliary beat frequency using optical flow (United States)

    Figl, Michael; Lechner, Manuel; Werther, Tobias; Horak, Fritz; Hummel, Johann; Birkfellner, Wolfgang


    Ciliary beat frequency (CBF) can be a useful parameter for diagnosis of several diseases, as e.g. primary ciliary dyskinesia. (PCD). CBF computation is usually done using manual evaluation of high speed video sequences, a tedious, observer dependent, and not very accurate procedure. We used the OpenCV's pyramidal implementation of the Lukas-Kanade algorithm for optical flow computation and applied this to certain objects to follow the movements. The objects were chosen by their contrast applying the corner detection by Shi and Tomasi. Discrimination between background/noise and cilia by a frequency histogram allowed to compute the CBF. Frequency analysis was done using the Fourier transform in matlab. The correct number of Fourier summands was found by the slope in an approximation curve. The method showed to be usable to distinguish between healthy and diseased samples. However there remain difficulties in automatically identifying the cilia, and also in finding enough high contrast cilia in the image. Furthermore the some of the higher contrast cilia are lost (and sometimes found) by the method, an easy way to distinguish the correct sub-path of a point's path have yet to be found in the case where the slope methods doesn't work.

  13. Methods for Studying Ciliary-Mediated Chemoresponse in Paramecium. (United States)

    Valentine, Megan Smith; Van Houten, Judith L


    Paramecium is a useful model organism for the study of ciliary-mediated chemical sensing and response. Here we describe ways to take advantage of Paramecium to study chemoresponse.Unicellular organisms like the ciliated protozoan Paramecium sense and respond to chemicals in their environment (Van Houten, Ann Rev Physiol 54:639-663, 1992; Van Houten, Trends Neurosci 17:62-71, 1994). A thousand or more cilia that cover Paramecium cells serve as antennae for chemical signals, similar to ciliary function in a large variety of metazoan cell types that have primary or motile cilia (Berbari et al., Curr Biol 19(13):R526-R535, 2009; Singla V, Reiter J, Science 313:629-633, 2006). The Paramecium cilia also produce the motor output of the detection of chemical cues by controlling swimming behavior. Therefore, in Paramecium the cilia serve multiple roles of detection and response.We present this chapter in three sections to describe the methods for (1) assaying populations of cells for their behavioral responses to chemicals (attraction and repulsion), (2) characterization of the chemoreceptors and associated channels of the cilia using proteomics and binding assays, and (3) electrophysiological analysis of individual cells' responses to chemicals. These methods are applied to wild type cells, mutants, transformed cells that express tagged proteins, and cells depleted of gene products by RNA Interference (RNAi).

  14. Disruption of a Ciliary B9 Protein Complex Causes Meckel Syndrome (United States)

    Dowdle, William E.; Robinson, Jon F.; Kneist, Andreas; Sirerol-Piquer, M. Salomé; Frints, Suzanna G.M.; Corbit, Kevin C.; Zaghloul, Norran A.; van Lijnschoten, Gesina; Mulders, Leon; Verver, Dideke E.; Zerres, Klaus; Reed, Randall R.; Attié-Bitach, Tania; Johnson, Colin A.; García-Verdugo, José Manuel; Katsanis, Nicholas; Bergmann, Carsten; Reiter, Jeremy F.


    Nearly every ciliated organism possesses three B9 domain-containing proteins: MKS1, B9D1, and B9D2. Mutations in human MKS1 cause Meckel syndrome (MKS), a severe ciliopathy characterized by occipital encephalocele, liver ductal plate malformations, polydactyly, and kidney cysts. Mouse mutations in either Mks1 or B9d2 compromise ciliogenesis and result in phenotypes similar to those of MKS. Given the importance of these two B9 proteins to ciliogenesis, we examined the role of the third B9 protein, B9d1. Mice lacking B9d1 displayed polydactyly, kidney cysts, ductal plate malformations, and abnormal patterning of the neural tube, concomitant with compromised ciliogenesis, ciliary protein localization, and Hedgehog (Hh) signal transduction. These data prompted us to screen MKS patients for mutations in B9D1 and B9D2. We identified a homozygous c.301A>C (p.Ser101Arg) B9D2 mutation that segregates with MKS, affects an evolutionarily conserved residue, and is absent from controls. Unlike wild-type B9D2 mRNA, the p.Ser101Arg mutation failed to rescue zebrafish phenotypes induced by the suppression of b9d2. With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. Our data indicate that B9d1 is required for normal Hh signaling, ciliogenesis, and ciliary protein localization and that B9d1 and B9d2 are essential components of a B9 protein complex, disruption of which causes MKS. PMID:21763481

  15. High-frequency ultrasound measurements of the normal ciliary body and iris. (United States)

    Garcia, Julian P S; Spielberg, Leigh; Finger, Paul T


    To determine the normal ultrasonographic thickness of the iris and ciliary body. This prospective 35-MHz ultrasonographic study included 80 normal eyes of 40 healthy volunteers. The images were obtained at the 12-, 3-, 6-, and 9-o'clock radial meridians, measured at three locations along the radial length of the iris and at the thickest section of the ciliary body. Mixed model was used to estimate eye site-adjusted means and standard errors and to test the statistical difference of adjusted results. Parameters included mean thickness, standard deviation, and range. Mean thicknesses at the iris root, midway along the radial length of the iris, and at the juxtapupillary margin were 0.4 ± 0.1, 0.5 ± 0.1, and 0.6 ± 0.1 mm, respectively. Those of the ciliary body, ciliary processes, and ciliary body + ciliary processes were 0.7 ± 0.1, 0.6 ± 0.1, and 1.3 ± 0.2 mm, respectively. This study provides standard, normative thickness data for the iris and ciliary body in healthy adults using ultrasonographic imaging. Copyright 2011, SLACK Incorporated.

  16. Airway ciliary dysfunction and respiratory symptoms in patients with transposition of the great arteries. (United States)

    Zahid, Maliha; Bais, Abha; Tian, Xin; Devine, William; Lee, Dong Ming; Yau, Cyrus; Sonnenberg, Daniel; Beerman, Lee; Khalifa, Omar; Lo, Cecilia W


    Our prior work on congenital heart disease (CHD) with heterotaxy, a birth defect involving randomized left-right patterning, has shown an association of a high prevalence of airway ciliary dysfunction (CD; 18/43 or 42%) with increased respiratory symptoms. Furthermore, heterotaxy patients with ciliary dysfunction were shown to have more postsurgical pulmonary morbidities. These findings are likely a reflection of the common role of motile cilia in both airway clearance and left-right patterning. As CHD comprising transposition of the great arteries (TGA) is commonly thought to involve disturbance of left-right patterning, especially L-TGA with left-right ventricular inversion, we hypothesize CHD patients with transposition of great arteries (TGA) may have high prevalence of airway CD with increased respiratory symptoms. We recruited 75 CHD patients with isolated TGA, 28% L and 72% D-TGA. Patients were assessed using two tests typically used for evaluating airway ciliary dysfunction in patients with primary ciliary dyskinesia (PCD), a recessive sinopulmonary disease caused by respiratory ciliary dysfunction. This entailed the measurement of nasal nitric oxide (nNO), which is typically low with PCD. We also obtained nasal scrapes and conducted videomicroscopy to assess respiratory ciliary motion (CM). We observed low nNO in 29% of the patients, and abnormal CM in 57%, with 22% showing both low nNO and abnormal CM. No difference was observed for the prevalence of either low nNO or abnormal ciliary motion between patients with D vs. L-TGA. Respiratory symptoms were increased with abnormal CM, but not low nNO. Sequencing analysis showed no compound heterozygous or homozygous mutations in 39 genes known to cause PCD, nor in CFTR, gene causing cystic fibrosis. As both are recessive disorders, these results indicate TGA patients with ciliary dysfunction do not have PCD or cystic fibrosis (which can cause low nNO or abnormal ciliary motion). TGA patients have high

  17. Measurement of ciliary beat frequency using Doppler optical coherence tomography. (United States)

    Lemieux, Bryan T; Chen, Jason J; Jing, Joseph; Chen, Zhongping; Wong, Brian J F


    Measuring ciliary beat frequency (CBF) is a technical challenge and difficult to perform in vivo. Doppler optical coherence tomography (D-OCT) is a mesoscopic noncontact imaging modality that provides high-resolution tomographic images and detects micromotion simultaneously in living tissues. In this work we used D-OCT to measure CBF in ex vivo tissue as the first step toward translating this technology to clinical use. Fresh ex vivo samples of rabbit tracheal mucosa were imaged using both D-OCT and phase-contrast microscopy (n = 5). The D-OCT system was designed and built to specification in our lab (1310-nm swept source vertical-cavity surface-emitting laser [VCSEL], 6-μm axial resolution). The samples were placed in culture and incubated at 37°C. A fast Fourier transform was performed on the D-OCT signal recorded on the surface of the samples to gauge CBF. High-speed digital video of the epithelium recorded via phase-contrast microscopy was analyzed to confirm the CBF measurements. The D-OCT system detected Doppler signal at the epithelial layer of ex vivo rabbit tracheal samples suggestive of ciliary motion. CBF was measured at 9.36 ± 1.22 Hz using D-OCT and 9.08 ± 0.48 Hz using phase-contrast microscopy. No significant differences were found between the 2 methods (p > 0.05). D-OCT allows for the quantitative measurement of CBF without the need to resolve individual cilia. Furthermore, D-OCT technology can be incorporated into endoscopic platforms that allow clinicians to readily measure CBF in the office and provide a direct measurement of mucosal health. © 2015 ARS-AAOA, LLC.

  18. Genotypic variation for salinity tolerance in Cenchrus ciliaris L

    Directory of Open Access Journals (Sweden)

    M. Iftikhar Hussain


    Full Text Available Scarcity of irrigation water and increasing soil salinization has threatened the sustainability of forage production in arid and semi-arid region around the globe. Introduction of salt-tolerant perennial species is a promising alternative to overcome forage deficit to meet future livestock needs in salt-affected areas. This study presents the results of a salinity tolerance screening trial which was carried out in plastic pots buried in the open field for 160 buffelgrass (Cenchrus ciliaris L. accessions for three consecutive years (2003-2005. The plastic pots were filled with sand, organic, and peat moss mix and were irrigated with four different quality water (EC 0, 10, 15, and 20 dS m-1. The results indicate that the average annual dry weights (DW were in the range from 122.5 – 148.9 g pot-1 in control; 96.4 – 133.8 g pot-1 at 10 dS m-1; 65.6 – 80.4 g pot-1 at 15 dS m-1, and 55.4- 65.6 g pot-1 at 20 dS m-1. The highest DW (148.9 g pot-1 was found with accession 49 and the lowest with accession 23. Principle component analysis shows that PC-1 contributed 81.8 % of the total variability, while PC-2 depicted 11.7% of the total variation among C. ciliaris accessions for DW. Hierarchical cluster analysis revealed that a number of accessions collected from diverse regions could be grouped into a single cluster. Accessions 3, 133, 159, 30, 23, 142, 141, 95, 49, 129, 124, and 127 were stable, salt tolerant, and produced good dry biomass yield. These accessions demonstrate sufficient salinity tolerance potential for promotion in marginal land and arid regions to enhance farm productivity and reduce rural poverty.

  19. Simultaneous sinus and lung infections in patients with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Alanin, Mikkel Christian; Johansen, Helle Krogh; Aanaes, Kasper


    Conclusion: The sinuses should be considered as a bacterial reservoir and a target for surgery and antibiotic treatment in patients with primary ciliary dyskinesia (PCD). The observed decrease in serum precipitating antibodies (precipitins) against Pseudomonas aeruginosa may indicate a beneficial...

  20. Circumferential Ciliary Body Cysts Presenting as Acute Pigment Dispersion and Ocular Hypertension. (United States)

    Sarıgül Sezenöz, Almila; Güngör, Sirel Gür; Kıratlı, Hayyam; Akman, Ahmet


    To report a case of circumferential neuroepithelial cyst of the ciliary body presenting with pigment dispersion (PD) and ocular hypertension. 48-year-old female patient presented with a complaint of pain in the left eye. On examination, visual acuity of the left eye was 0.9, and the intraocular pressure was 48 mmHg. Biomicroscopic anterior segment examination of the left eye revealed 4+ pigmented cells in the anterior chamber. Active PD from the pupillary region at 11 o'clock was noticed at the time of the examination. Ultrasound biomicroscopy demonstrated 360º cystic lesions of the ciliary body in the left eye. The patient was diagnosed as neuroepithelial cyst of the ciliary body. Our case is unique as it is the first case of circumferential neuroepithelial ciliary body cyst presenting with acute PD and ocular hypertension.

  1. ICK is essential for cell type-specific ciliogenesis and the regulation of ciliary transport. (United States)

    Chaya, Taro; Omori, Yoshihiro; Kuwahara, Ryusuke; Furukawa, Takahisa


    Cilia and flagella are formed and maintained by intraflagellar transport (IFT) and play important roles in sensing and moving across species. At the distal tip of the cilia/flagella, IFT complexes turn around to switch from anterograde to retrograde transport; however, the underlying regulatory mechanism is unclear. Here, we identified ICK localization at the tip of cilia as a regulator of ciliary transport. In ICK-deficient mice, we found ciliary defects in neuronal progenitor cells with Hedgehog signal defects. ICK-deficient cells formed cilia with mislocalized Hedgehog signaling components. Loss of ICK caused the accumulation of IFT-A, IFT-B, and BBSome components at the ciliary tips. In contrast, overexpression of ICK induced the strong accumulation of IFT-B, but not IFT-A or BBSome components at ciliary tips. In addition, ICK directly phosphorylated Kif3a, while inhibition of this Kif3a phosphorylation affected ciliary formation. Our results suggest that ICK is a Kif3a kinase and essential for proper ciliogenesis in development by regulating ciliary transport at the tip of cilia. © 2014 The Authors.

  2. SRS-A leukotrienes decrease the activity of human respiratory cilia

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, M


    We have studied the effects of the slow reacting substance of anaphylaxis (SRS-A) constituents leukotrienes (LT) C4 and D4 on the ciliary activity of human respiratory cells. The ciliary beat frequency on human nasal cells harvested by cell scraping from the inferior turbinate was measured...

  3. Extração, análise e distribuição dos ácidos fenólicos em genótipos pigmentados e não pigmentados de arroz (Oryza sativa L. Extraction, analysis and distribution of phenolic acids in pigmented and non-pigmented genotypes of rice (Oryza sativa L.

    Directory of Open Access Journals (Sweden)

    Nádia Valéria Mussi de Mira


    Full Text Available Neste estudo, avaliaram-se a distribuição dos Compostos Fenólicos Totais (CFT e o perfil de ácidos fenólicos, presentes nas frações, solúvel e insolúvel de dez genótipos de arroz (Oryza sativa L. de pericarpo pigmentado e não pigmentado. Devido à sua elevada capacidade antioxidante, os compostos fenólicos vem sendo apontados como possíveis promotores da saúde. Grande parte corresponde aos ácidos fenólicos presentes no grão sob a forma solúvel (livre e conjugada e insolúvel (ligada. Na literatura há poucas informações sobre a contribuição dos compostos fenólicos ligados, cujos teores são costumeiramente subestimados. Os CFT foram quantificados pelo método de Folin-Ciocalteau, enquanto os ácidos fenólicos por RP-HPLC. Na fração solúvel dos genótipos pigmentados, os teores de CFT foram variáveis, mas, em média, 5,7 vezes maiores do que nos não pigmentados (média de 3468 e 602 µg eq. Ácido Ferúlico (AF/g arroz, respectivamente, principalmente devido à presença de antocianinas e proantocianidinas. Na fração insolúvel, os pigmentados apresentaram duas vezes mais CFT do que os não pigmentados (825 e 378 µg eq. AF/g arroz, respectivamente, provavelmente devido à retenção de antocianinas e proantocianidinas, mesmo após cinco extrações consecutivas. Dentre os ácidos fenólicos, o ácido ferúlico foi o principal componente em todos os genótipos estudados, exceto no arroz preto, no qual predominou o ácido protocatecóico.This study was conducted to evaluate the distribution of total phenolic compounds and phenolic acids in the soluble and insoluble fractions of 10 rice (Oryza sativa L. genotypes with pigmented or non-pigmented pericarp. These compounds were reported to exert beneficial effects on human health due to their high antioxidant activities. The total phenolic compounds (CFT in both fractions was determined by the Folin-Ciocalteau method and phenolic acids RP-HPLC with Diode-Array Detection

  4. Acute versus chronic loss of mammalian Azi1/Cep131 results in distinct ciliary phenotypes.

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    Emma A Hall

    Full Text Available Defects in cilium and centrosome function result in a spectrum of clinically-related disorders, known as ciliopathies. However, the complex molecular composition of these structures confounds functional dissection of what any individual gene product is doing under normal and disease conditions. As part of an siRNA screen for genes involved in mammalian ciliogenesis, we and others have identified the conserved centrosomal protein Azi1/Cep131 as required for cilia formation, supporting previous Danio rerio and Drosophila melanogaster mutant studies. Acute loss of Azi1 by knock-down in mouse fibroblasts leads to a robust reduction in ciliogenesis, which we rescue by expressing siRNA-resistant Azi1-GFP. Localisation studies show Azi1 localises to centriolar satellites, and traffics along microtubules becoming enriched around the basal body. Azi1 also localises to the transition zone, a structure important for regulating traffic into the ciliary compartment. To study the requirement of Azi1 during development and tissue homeostasis, Azi1 null mice were generated (Azi1(Gt/Gt. Surprisingly, Azi1(Gt/Gt MEFs have no discernible ciliary phenotype and moreover are resistant to Azi1 siRNA knock-down, demonstrating that a compensation mechanism exists to allow ciliogenesis to proceed despite the lack of Azi1. Cilia throughout Azi1 null mice are functionally normal, as embryonic patterning and adult homeostasis are grossly unaffected. However, in the highly specialised sperm flagella, the loss of Azi1 is not compensated, leading to striking microtubule-based trafficking defects in both the manchette and the flagella, resulting in male infertility. Our analysis of Azi1 knock-down (acute loss versus gene deletion (chronic loss suggests that Azi1 plays a conserved, but non-essential trafficking role in ciliogenesis. Importantly, our in vivo analysis reveals Azi1 mediates novel trafficking functions necessary for flagellogenesis. Our study highlights the

  5. Hearing loss in children with primary ciliary dyskinesia. (United States)

    Kreicher, Kathryn L; Schopper, Heather K; Naik, Akash N; Hatch, Jonathan L; Meyer, Ted A


    To evaluate the type and severity of hearing impairment in pediatric patients with primary ciliary dyskinesia (PCD) and relate these measures to patient demographics, treatment options, and other otologic factors. A retrospective analysis of children with a diagnosis of PCD, Kartagener's syndrome, or situs inversus in the AudGen Database was conducted. Audiograms were analyzed for type of hearing loss (HL), severity, laterality, and progression. Medical charts were reviewed to identify factors that influence severity and progression of hearing loss. 56 patients met inclusion criteria and 42 patients had HL. 66.6% had bilateral and 33.3% had unilateral loss (70 total ears with HL). Conductive hearing loss (CHL) was the most common type of HL, though 30% of children had some sensorineural component to their hearing loss. 92.9% of children with HL received at least one diagnosis of otitis media, but HL did not improve in the majority (77.8%) of ears in our study regardless of ear tube placement. Slight to mild CHL and all types of otitis media are prevalent among patients with PCD, and some of these children have sensorineural hearing loss (SNHL). All patients diagnosed with situs inversus at birth should be evaluated by an otolaryngologist. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Inactivation of Ca2+-induced ciliary reversal by high-salt extraction in the cilia of Paramecium. (United States)

    Kutomi, Osamu; Seki, Makoto; Nakamura, Shogo; Kamachi, Hiroyuki; Noguchi, Munenori


    Intracellular Ca(2+) induces ciliary reversal and backward swimming in Paramecium. However, it is not known how the Ca(2+) signal controls the motor machinery to induce ciliary reversal. We found that demembranated cilia on the ciliated cortical sheets from Paramecium caudatum lost the ability to undergo ciliary reversal after brief extraction with a solution containing 0.5 M KCl. KNO(3), which is similar to KCl with respect to chaotropic effect; it had the same effect as that of KCl on ciliary response. Cyclic AMP antagonizes Ca(2+)-induced ciliary reversal. Limited trypsin digestion prevents endogenous A-kinase and cAMP-dependent phosphorylation of an outer arm dynein light chain and induces ciliary reversal. However, the trypsin digestion prior to the high-salt extraction did not affect the inhibition of Ca(2+)-induced ciliary reversal caused by the high-salt extraction. Furthermore, during the course of the high-salt extraction, some axonemal proteins were extracted from ciliary axonemes, suggesting that they may be responsible for Ca(2+)-induced ciliary reversal.

  7. cAMP Stimulates Transepithelial Short-Circuit Current and Fluid Transport Across Porcine Ciliary Epithelium. (United States)

    Cheng, Angela King-Wah; Civan, Mortimer M; To, Chi-Ho; Do, Chi-Wai


    To investigate the effects of cAMP on transepithelial electrical parameters and fluid transport across porcine ciliary epithelium. Transepithelial electrical parameters were determined by mounting freshly isolated porcine ciliary epithelium in a modified Ussing chamber. Similarly, fluid movement across intact ciliary body was measured with a custom-made fluid flow chamber. Addition of 1, 10, and 100 μM 8-Br-cAMP (cAMP) to the aqueous side (nonpigmented ciliary epithelium, NPE) induced a sustained increase in short-circuit current (Isc). Addition of niflumic acid (NFA) to the aqueous surface effectively blocked the cAMP-induced Isc stimulation. The administration of cAMP to the stromal side (pigmented ciliary epithelium, PE) triggered a significant stimulation of Isc only at 100 μM. No additive effect was observed with bilateral application of cAMP. Likewise, forskolin caused a significant stimulation of Isc when applied to the aqueous side. Concomitantly, cAMP and forskolin increased fluid transport across porcine ciliary epithelium, and this stimulation was effectively inhibited by aqueous NFA. Depleting Cl- in the bathing solution abolished the baseline Isc and inhibited the subsequent stimulation by cAMP. Pretreatment with protein kinase A (PKA) blockers (H89/KT5720) significantly inhibited the cAMP- and forskolin-induced Isc responses. Our results suggest that cAMP triggers a sustained stimulation of Cl- and fluid transport across porcine ciliary epithelium; Cl- channels in the NPE cells are potentially a cellular site for this PKA-sensitive cAMP-mediated response.

  8. Up-regulation of Ciliary Neurotrophic Factor in Astrocytes by Aspirin (United States)

    Modi, Khushbu K.; Sendtner, Michael; Pahan, Kalipada


    Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor, and the mechanisms by which CNTF expression could be increased in the brain are poorly understood. Acetylsalicylic acid (aspirin) is one of the most widely used analgesics. Interestingly, aspirin increased mRNA and protein expression of CNTF in primary mouse and human astrocytes in a dose- and time-dependent manner. Aspirin induced the activation of protein kinase A (PKA) but not protein kinase C (PKC). H-89, an inhibitor of PKA, abrogated aspirin-induced expression of CNTF. The activation of cAMP-response element-binding protein (CREB), but not NF-κB, by aspirin, the abrogation of aspirin-induced expression of CNTF by siRNA knockdown of CREB, the presence of a consensus cAMP-response element in the promoter of CNTF, and the recruitment of CREB and CREB-binding protein to the CNTF promoter by aspirin suggest that aspirin increases the expression of the Cntf gene via the activation of CREB. Furthermore, we demonstrate that aspirin-induced astroglial CNTF was also functionally active and that supernatants of aspirin-treated astrocytes of wild type, but not Cntf null, mice increased myelin-associated proteins in oligodendrocytes and protected oligodendrocytes from TNF-α insult. These results highlight a new and novel myelinogenic property of aspirin, which may be of benefit for multiple sclerosis and other demyelinating disorders. PMID:23653362

  9. Patient-specific three-dimensional explant spheroids derived from human nasal airway epithelium

    DEFF Research Database (Denmark)

    Marthin, June Kehlet; Stevens, Elizabeth Munkebjerg; Larsen, Lars Allan


    BACKGROUND: Three-dimensional explant spheroid formation is an ex vivo technique previously used in studies of airway epithelial ion and water transport. Explanted cells and sheets of nasal epithelium form fully differentiated spheroids enclosing a partly fluid-filled lumen with the ciliated apical...... surface facing the outside and accessible for analysis of ciliary function. METHODS: We performed a two-group comparison study of ciliary beat pattern and ciliary beat frequency in spheroids derived from nasal airway epithelium in patients with primary ciliary dyskinesia (PCD) and in healthy controls...... in the investigation of pathophysiological aspects and drug effects in human nasal airway epithelium....

  10. Ciliary body toxicities of systemic oxcarbazepine and valproic acid treatments: electron microscopic study. (United States)

    Göktaş, Güleser; Aktaş, Zeynep; Erdoğan, Deniz; Seymen, Cemile Merve; Karaca, Emine Esra; Cansu, Ali; Serdaroğlu, Ayşe; Kaplanoğlu, Gülnur Take


    Ciliary body is responsible for humour aqueous production in posterior chamber. Valproic acid (VPA) has been widely used for the treatment of epilepsy and other neuropsychiatric diseases such as bipolar disease and major depression. Oxcarbazepine (OXC) is a new anti-epileptic agent that has been used recently for childhood epilepsies such as VPA. In this study, we aimed to investigate the effects of VPA and OXC treatments used as antiepileptic in ciliary body by electron microscopy. In our study, 40 Wistar rats (21 days old) were divided equally into four groups which were applied saline (group 1), VPA (group 2), OXC (group 3) and VPA + OXC (group 4). The as-prepared ocular tissues were characterized by transmission electron microscopy (TEM) technique in scanning and transmission electron microscopy (SEM-TEM) (Carl Zeiss EVO LS10). The results confirmed that VPA caused dense ciliary body degeneration. Additionally, ciliary body degeneration in group 4 was supposed to be due to VPA treatment. Ciliary body damage and secondary outcomes should be considered in patients with long-term VPA therapy.

  11. Rapid diagnosis of primary ciliary dyskinesia: cell culture and soft computing analysis. (United States)

    Pifferi, Massimo; Bush, Andrew; Montemurro, Francesca; Pioggia, Giovanni; Piras, Martina; Tartarisco, Gennaro; Di Cicco, Maria; Chinellato, Iolanda; Cangiotti, Angela M; Boner, Attilio L


    Diagnosis of primary ciliary dyskinesia (PCD) sometimes requires repeated nasal brushing to exclude secondary ciliary alterations. Our aim was to evaluate whether the use of a new method of nasal epithelial cell culture can speed PCD diagnosis in doubtful cases and to identify which are the most informative parameters by means of a multilayer artificial neural network (ANN). A cross-sectional study was performed in patients with suspected PCD. All patients underwent nasal brushing for ciliary motion analysis, ultrastructural assessment and evaluation of ciliary function after ciliogenesis in culture by ANN. 151 subjects were studied. A diagnostic suspension cell culture was obtained in 117 nasal brushings. A diagnosis of PCD was made in 36 subjects (29 of whom were children). In nine out of the 36 patients the diagnosis was made only after a second brushing, because of equivocal results of both tests at first examination. In each of these subjects diagnosis of PCD was confirmed by cell culture results. Cell culture in suspension evaluated by means of ANN allows the separation of PCD from secondary ciliary dyskinesia patients after only 5 days of culture and allows diagnosis to be reached in doubtful cases, thus avoiding the necessity of a second sample.

  12. Downstream collecting in ciliary suspension feeders: the catch-up principle

    DEFF Research Database (Denmark)

    Riisgård, Hans Ulrik; Nielsen, Claus; Larsen, Poul Scheel


    -size retention spectrum, the lower limit depends on spacing between cilia in phase, while the upper end depends on cilia length which may or may not allow particles to enter the ciliary region. On the basis of fluid mechanical considerations and literature descriptions of structure and function of the ciliary......Based on observations of feeding structures and currents in the polychaete Spirorbis tridentatus, the entoproct Loxosoma pectinaricola and the cycliophore Symbion pandora, which all possess compound cilia, it is hypothesized that their capture mechanism is based on the catch-up principle. According...... to this principle, the compound cilia constitute the pump which generates a flow with suspended particles that enters the ciliary region. In this region the same cilia, during their power stroke, catch up with suspended particles and transfer the particles to a food groove, or a mouth cavity. In the particle...

  13. Bacteriology and treatment of infections in the upper and lower airways in patients with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Alanin, Mikkel Christian


    The respiratory tract is lined with motile cilia that transport respiratory mucus. Primary ciliary dyskinesia (PCD) is a chronic genetic disease caused by mutations in genes responsible for ciliary structure and function. Non-functional airway cilia impair the mucociliary clearance (MCC), causing...

  14. A novel ICK mutation causes ciliary disruption and lethal endocrine-cerebro-osteodysplasia syndrome. (United States)

    Oud, Machteld M; Bonnard, Carine; Mans, Dorus A; Altunoglu, Umut; Tohari, Sumanty; Ng, Alvin Yu Jin; Eskin, Ascia; Lee, Hane; Rupar, C Anthony; de Wagenaar, Nathalie P; Wu, Ka Man; Lahiry, Piya; Pazour, Gregory J; Nelson, Stanley F; Hegele, Robert A; Roepman, Ronald; Kayserili, Hülya; Venkatesh, Byrappa; Siu, Victoria M; Reversade, Bruno; Arts, Heleen H


    Endocrine-cerebro-osteodysplasia (ECO) syndrome [MIM:612651] caused by a recessive mutation (p.R272Q) in Intestinal cell kinase (ICK) shows significant clinical overlap with ciliary disorders. Similarities are strongest between ECO syndrome, the Majewski and Mohr-Majewski short-rib thoracic dysplasia (SRTD) with polydactyly syndromes, and hydrolethalus syndrome. In this study, we present a novel homozygous ICK mutation in a fetus with ECO syndrome and compare the effect of this mutation with the previously reported ICK variant on ciliogenesis and cilium morphology. Through homozygosity mapping and whole-exome sequencing, we identified a second variant (c.358G > T; p.G120C) in ICK in a Turkish fetus presenting with ECO syndrome. In vitro studies of wild-type and mutant mRFP-ICK (p.G120C and p.R272Q) revealed that, in contrast to the wild-type protein that localizes along the ciliary axoneme and/or is present in the ciliary base, mutant proteins rather enrich in the ciliary tip. In addition, immunocytochemistry revealed a decreased number of cilia in ICK p.R272Q-affected cells. Through identification of a novel ICK mutation, we confirm that disruption of ICK causes ECO syndrome, which clinically overlaps with the spectrum of ciliopathies. Expression of ICK-mutated proteins result in an abnormal ciliary localization compared to wild-type protein. Primary fibroblasts derived from an individual with ECO syndrome display ciliogenesis defects. In aggregate, our findings are consistent with recent reports that show that ICK regulates ciliary biology in vitro and in mice, confirming that ECO syndrome is a severe ciliopathy.

  15. Long-term clearance from small airways in subjects with ciliary dysfunction


    Hjelte Lena; Falk Rolf; Lindström Maria; Philipson Klas; Svartengren Magnus


    Abstract The objective of this study was to investigate if long-term clearance from small airways is dependent on normal ciliary function. Six young adults with primary ciliary dyskinesia (PCD) inhaled 111 Indium labelled Teflon particles of 4.2 μm geometric and 6.2 μm aerodynamic diameter with an extremely slow inhalation flow, 0.05 L/s. The inhalation method deposits particles mainly in the small conducting airways. Lung retention was measured immediately after inhalation and at four occasi...

  16. Proteomic analysis of isolated chlamydomonas centrioles reveals orthologs of ciliary-disease genes. (United States)

    Keller, Lani C; Romijn, Edwin P; Zamora, Ivan; Yates, John R; Marshall, Wallace F


    The centriole is one of the most enigmatic organelles in the cell. Centrioles are cylindrical, microtubule-based barrels found in the core of the centrosome. Centrioles also act as basal bodies during interphase to nucleate the assembly of cilia and flagella. There are currently only a handful of known centriole proteins. We used mass-spectrometry-based MudPIT (multidimensional protein identification technology) to identify the protein composition of basal bodies (centrioles) isolated from the green alga Chlamydomonas reinhardtii. This analysis detected the majority of known centriole proteins, including centrin, epsilon tubulin, and the cartwheel protein BLD10p. By combining proteomic data with information about gene expression and comparative genomics, we identified 45 cross-validated centriole candidate proteins in two classes. Members of the first class of proteins (BUG1-BUG27) are encoded by genes whose expression correlates with flagellar assembly and which therefore may play a role in ciliogenesis-related functions of basal bodies. Members of the second class (POC1-POC18) are implicated by comparative-genomics and -proteomics studies to be conserved components of the centriole. We confirmed centriolar localization for the human homologs of four candidate proteins. Three of the cross-validated centriole candidate proteins are encoded by orthologs of genes (OFD1, NPHP-4, and PACRG) implicated in mammalian ciliary function and disease, suggesting that oral-facial-digital syndrome and nephronophthisis may involve a dysfunction of centrioles and/or basal bodies. By analyzing isolated Chlamydomonas basal bodies, we have been able to obtain the first reported proteomic analysis of the centriole.

  17. Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis.

    NARCIS (Netherlands)

    Hollander, A.I. den; Koenekoop, R.K.; Mohamed, M.D.; Arts, H.H.; Boldt, K.; Towns, K.V.; Sedmak, T.; Beer, M. de; Nagel-Wolfrum, K.; McKibbin, M.; Dharmaraj, S.; Lopez, I.; Ivings, L.; Williams, G.A.; Springell, K.; Woods, C.G.; Jafri, H.; Rashid, Y.; Strom, T.M.; Zwaag, B. van der; Gosens, I.; Kersten, F.F.J.; Wijk, E. van; Veltman, J.A.; Zonneveld, M.N.; Beersum, S.E.C. van; Maumenee, I.H.; Wolfrum, U.; Cheetham, M.E.; Ueffing, M.; Cremers, F.P.M.; Inglehearn, C.F.; Roepman, R.


    Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We

  18. A longitudinal evaluation of hearing and ventilation tube insertion in patients with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Andersen, Tobias Nicolai; Alanin, Mikkel Christian; von Buchwald, Christian


    INTRODUCTION: Primary ciliary dyskinesia (PCD) is an autosomal recessive genetic disease, which primarily manifests with oto-sino-pulmonary symptoms. Otitis media with effusion (OME) is common from early childhood. The existing literature on OME management in PCD is conflicting. The goals of the ...

  19. ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6

    DEFF Research Database (Denmark)

    Zariwala, Maimoona A; Gee, Heon Yung; Kurkowiak, Małgorzata


    Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the ...

  20. Target recognition and synapse formation by ciliary-ganglion neurons in tissue culture

    NARCIS (Netherlands)

    Stevens, W.F.; Slaaf, D.W.; Hooisma, J.; Magchielse, T.; Meeter, E.


    A less complicated source of neurons suitable for this type of studies is the parasympathetic ciliary ganglion. In the pigeon and in the chick this ganglion is known to contain only two classes of neurons, both of which are cholinoceptive and cholinergic and that innervate the muscle fibres of the

  1. Multicenter analysis of body mass index, lung function, and sputum microbiology in primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Maglione, Marco; Bush, Andrew; Nielsen, Kim G


    BACKGROUND: No studies longitudinally, simultaneously assessed body mass index (BMI) and spirometry in primary ciliary dyskinesia (PCD). METHODS: We determined BMI and spirometry in 158 PCD children and adolescents from London, UK (n = 75), Naples, Italy (n = 23) and Copenhagen, Denmark (n = 60) ...

  2. Growth of the crabgrass species Digitaria ciliaris and Digitaria nuda Crescimento das espécies de capim-colchão Digitaria ciliaris e Digitaria nuda

    Directory of Open Access Journals (Sweden)

    R.C. Souza


    Full Text Available The aim of this research paper was to compare the growth of D. ciliaris and D. nuda crabgrass species under non-competitive conditions. To this end, two experiments were conducted, one from March - July 2010 and the other from February - June 2011. The experimental design of both trials was completely randomized making a factorial (2 seasons x 2 species crabgrass x 12 evaluation periods with four replications. Assessments began at 15 days after sowing (DAS, and repeated weekly until 92 DAS. The variables evaluated were total dry matter (roots+leaves+stems, leaf area, leaf number and tiller. The results were submitted to analysis of variance and the absolute growth rate, relative growth rate and leaf area ratio were calculated using the means, which were adjusted regression models. The crabgrass species were significantly different in leaf area, leaf number, tiller number and dry matter per plant. D. ciliaris for all variables was statistically higher than D. nuda. Regarding the speed at which the growth of the species occurred, the absolute growth rate and relative growth rate of D. ciliaris was also greater than D. nuda. In addition, D. ciliaris also had a lower leaf area ratio indicating greater efficiency in converting light energy into carbohydrates. It can be concluded that D. ciliaris has a higher growth rate in conditions where there is no limitation of nutrients and water availability in relation to D. nuda, mainly due to D. ciliaris have greater leaf area, number of leaves and dry matter accumulation per plant.O objetivo da presente pesquisa foi comparar o crescimento das espécies de capim colchão D. ciliaris e D. nuda, em condições não-competitivas. Para isso, foram conduzidos dois experimentos, um de março a julho de 2010 e outro de fevereiro a junho de 2011. O delineamento experimental de ambos os ensaios foi inteiramente casualizado, perfazendo um esquema fatorial (2 épocas x 2 espécies de capim colchão x 12 períodos de

  3. The Meckel syndrome- associated protein MKS1 functionally interacts with components of the BBSome and IFT complexes to mediate ciliary trafficking and hedgehog signaling (United States)

    Barrington, Chloe L.; Katsanis, Nicholas


    The importance of primary cilia in human health is underscored by the link between ciliary dysfunction and a group of primarily recessive genetic disorders with overlapping clinical features, now known as ciliopathies. Many of the proteins encoded by ciliopathy-associated genes are components of a handful of multi-protein complexes important for the transport of cargo to the basal body and/or into the cilium. A key question is whether different complexes cooperate in cilia formation, and whether they participate in cilium assembly in conjunction with intraflagellar transport (IFT) proteins. To examine how ciliopathy protein complexes might function together, we have analyzed double mutants of an allele of the Meckel syndrome (MKS) complex protein MKS1 and the BBSome protein BBS4. We find that Mks1; Bbs4 double mutant mouse embryos exhibit exacerbated defects in Hedgehog (Hh) dependent patterning compared to either single mutant, and die by E14.5. Cells from double mutant embryos exhibit a defect in the trafficking of ARL13B, a ciliary membrane protein, resulting in disrupted ciliary structure and signaling. We also examined the relationship between the MKS complex and IFT proteins by analyzing double mutant between Mks1 and a hypomorphic allele of the IFTB component Ift172. Despite each single mutant surviving until around birth, Mks1; Ift172avc1 double mutants die at mid-gestation, and exhibit a dramatic failure of cilia formation. We also find that Mks1 interacts genetically with an allele of Dync2h1, the IFT retrograde motor. Thus, we have demonstrated that the MKS transition zone complex cooperates with the BBSome to mediate trafficking of specific trans-membrane receptors to the cilium. Moreover, the genetic interaction of Mks1 with components of IFT machinery suggests that the transition zone complex facilitates IFT to promote cilium assembly and structure. PMID:28291807

  4. The Meckel syndrome- associated protein MKS1 functionally interacts with components of the BBSome and IFT complexes to mediate ciliary trafficking and hedgehog signaling.

    Directory of Open Access Journals (Sweden)

    Sarah C Goetz

    Full Text Available The importance of primary cilia in human health is underscored by the link between ciliary dysfunction and a group of primarily recessive genetic disorders with overlapping clinical features, now known as ciliopathies. Many of the proteins encoded by ciliopathy-associated genes are components of a handful of multi-protein complexes important for the transport of cargo to the basal body and/or into the cilium. A key question is whether different complexes cooperate in cilia formation, and whether they participate in cilium assembly in conjunction with intraflagellar transport (IFT proteins. To examine how ciliopathy protein complexes might function together, we have analyzed double mutants of an allele of the Meckel syndrome (MKS complex protein MKS1 and the BBSome protein BBS4. We find that Mks1; Bbs4 double mutant mouse embryos exhibit exacerbated defects in Hedgehog (Hh dependent patterning compared to either single mutant, and die by E14.5. Cells from double mutant embryos exhibit a defect in the trafficking of ARL13B, a ciliary membrane protein, resulting in disrupted ciliary structure and signaling. We also examined the relationship between the MKS complex and IFT proteins by analyzing double mutant between Mks1 and a hypomorphic allele of the IFTB component Ift172. Despite each single mutant surviving until around birth, Mks1; Ift172avc1 double mutants die at mid-gestation, and exhibit a dramatic failure of cilia formation. We also find that Mks1 interacts genetically with an allele of Dync2h1, the IFT retrograde motor. Thus, we have demonstrated that the MKS transition zone complex cooperates with the BBSome to mediate trafficking of specific trans-membrane receptors to the cilium. Moreover, the genetic interaction of Mks1 with components of IFT machinery suggests that the transition zone complex facilitates IFT to promote cilium assembly and structure.

  5. Regulation of anterior chamber drainage by bicarbonate-sensitive soluble adenylyl cyclase in the ciliary body. (United States)

    Lee, Yong S; Tresguerres, Martin; Hess, Kenneth; Marmorstein, Lihua Y; Levin, Lonny R; Buck, Jochen; Marmorstein, Alan D


    Glaucoma is a leading cause of blindness affecting as many as 2.2 million Americans. All current glaucoma treatment strategies aim to reduce intraocular pressure (IOP). IOP results from the resistance to drainage of aqueous humor (AH) produced by the ciliary body in a process requiring bicarbonate. Once secreted into the anterior chamber, AH drains from the eye via two pathways: uveoscleral and pressure-dependent or conventional outflow (C(t)). Modulation of "inflow" and "outflow" pathways is thought to occur via distinct, local mechanisms. Mice deficient in the bicarbonate channel bestrophin-2 (Best2), however, exhibit a lower IOP despite an increase in AH production. Best2 is expressed uniquely in nonpigmented ciliary epithelial (NPE) cells providing evidence for a bicarbonate-dependent communicative pathway linking inflow and outflow. Here, we show that bicarbonate-sensitive soluble adenylyl cyclase (sAC) is highly expressed in the ciliary body in NPE cells, but appears to be absent from drainage tissues. Pharmacologic inhibition of sAC in mice causes a significant increase in IOP due to a decrease in C(t) with no effect on inflow. In mice deficient in sAC IOP is elevated, and C(t) is decreased relative to wild-type mice. Pharmacologic inhibition of sAC did not alter IOP or C(t) in sAC-deficient mice. Based on these data we propose that the ciliary body can regulate C(t) and that sAC serves as a critical sensor of bicarbonate in the ciliary body regulating the secretion of substances into the AH that govern outflow facility independent of pressure.

  6. Protein Interaction Analysis Provides a Map of the Spatial and Temporal Organization of the Ciliary Gating Zone. (United States)

    Takao, Daisuke; Wang, Liang; Boss, Allison; Verhey, Kristen J


    The motility and signaling functions of the primary cilium require a unique protein and lipid composition that is determined by gating mechanisms localized at the base of the cilium. Several protein complexes localize to the gating zone and may regulate ciliary protein composition; however, the mechanisms of ciliary gating and the dynamics of the gating components are largely unknown. Here, we used the BiFC (bimolecular fluorescence complementation) assay and report for the first time on the protein-protein interactions that occur between ciliary gating components and transiting cargoes during ciliary entry. We find that the nucleoporin Nup62 and the C termini of the nephronophthisis (NPHP) proteins NPHP4 and NPHP5 interact with the axoneme-associated kinesin-2 motor KIF17 and thus spatially map to the inner region of the ciliary gating zone. Nup62 and NPHP4 exhibit rapid turnover at the transition zone and thus define dynamic components of the gate. We find that B9D1, AHI1, and the N termini of NPHP4 and NPHP5 interact with the transmembrane protein SSTR3 and thus spatially map to the outer region of the ciliary gating zone. B9D1, AHI1, and NPHP5 exhibit little to no turnover at the transition zone and thus define components of a stable gating structure. These data provide the first comprehensive map of the molecular orientations of gating zone components along the inner-to-outer axis of the ciliary gating zone. These results advance our understanding of the functional roles of gating zone components in regulating ciliary protein composition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Longitudinal study of lung function in a cohort of primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Ellerman, A; Bisgaard, H


    Patients with primary ciliary dyskinesia (PCD) have pronounced stasis of their respiratory secretions and therefore recurrent lower airway infections, which raises concerns for the development of lung function. Twenty four patients with PCD have been studied prospectively with a standardized regime...... patients entering as children (forced vital capacity (FVC) 70 versus 85% predicted; forced expiratory volume in one second (FEV1) 59 versus 72% pred). The lung damage did not relate to the type of ciliary dyskinesia. During the subsequent surveillance of the groups for a median of 14 and 7 yrs...... in our clinic for 2-16 yrs with clinic visits, including spirometry 2-4 times per year, daily physiotherapy and monthly sputum cultures with subsequent specific antibiotic treatment. Lung function was significantly lower in the 12 PCD patients entering the cohort as adults when compared to the PCD...

  8. Ultrastructural alterations in ciliary cells exposed to ionizing radiation. A scanning and transmission electron microscopic study

    Energy Technology Data Exchange (ETDEWEB)

    Baldetorp, L; Mecklenburg, C v; Haakansson, C H [Lund Univ. (Sweden). Hospital; Lund Univ. (Sweden). Dept. of Zoology)


    Early effects of ionizing radiation were investigated in an experimental in vitro system using the ciliary cells of the tracheal mucous membrane of the rabbit, irradiated at 30/sup 0/C and at more than 90% humidity. The changes in physiological activities of the ciliary cells caused by irradation were continously registered during the irradation. The specimens were examined immediately after irradiation electron microscopically. The morphological changes in irradiated material after 10-70 Gy are compared with normal material. After 40-70 Gy, scanning electron microscopy revealed the formation of vesicles on cilia, and club-like protrusions and adhesion of their tips. After 30-70 Gy, a swelling of mitochondrial membranes and cristae was apparent transmission electron microscopically. The membrane alterations caused by irradiation are assumed to disturb the permeability and flow of ATP from the mitochondria, which in turn leads to the recorded changes in the activity of the ciliated cells.

  9. Continued administration of ciliary neurotrophic factor protects mice from inflammatory pathology in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Kuhlmann, Tanja; Remington, Leah; Cognet, Isabelle


    Multiple sclerosis is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. We show that daily administration (days 8 to 24) of murine ciliary neurotrophic factor (CNTF), a neurotrophic factor that has been described as a surv......Multiple sclerosis is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. We show that daily administration (days 8 to 24) of murine ciliary neurotrophic factor (CNTF), a neurotrophic factor that has been described...... it was withdrawn. After cessation of CNTF treatment, inflammation and symptoms returned to control levels. However, slight but significantly higher numbers of oligodendrocytes, NG2-positive cells, axons, and neurons were observed in mice that had been treated with high concentrations of CNTF. Our results show...

  10. Impact of the Smoothened inhibitor, IPI-926, on smoothened ciliary localization and Hedgehog pathway activity.

    Directory of Open Access Journals (Sweden)

    Marisa O Peluso

    Full Text Available A requisite step for canonical Hedgehog (Hh pathway activation by Sonic Hedgehog (Shh ligand is accumulation of Smoothened (Smo to the primary cilium (PC. Activation of the Hh pathway has been implicated in a broad range of cancers, and several Smo antagonists are being assessed clinically, one of which is approved for the treatment of advanced basal cell carcinoma. Recent reports demonstrate that various Smo antagonists differentially impact Smo localization to the PC while still exerting inhibitory activity. In contrast to other synthetic small molecule Smo antagonists, the natural product cyclopamine binds to and promotes ciliary accumulation of Smo and "primes" cells for Hh pathway hyper-responsiveness after compound withdrawal. We compared the properties of IPI-926, a semi-synthetic cyclopamine analog, to cyclopamine with regard to potency, ciliary Smo accumulation, and Hh pathway activity after compound withdrawal. Like cyclopamine, IPI-926 promoted accumulation of Smo to the PC. However, in contrast to cyclopamine, IPI-926 treatment did not prime cells for hyper-responsiveness to Shh stimulation after compound withdrawal, but instead demonstrated continuous inhibition of signaling. By comparing the levels of drug-induced ciliary Smo accumulation with the degree of Hh pathway activity after compound withdrawal, we propose that a critical threshold of ciliary Smo is necessary for "priming" activity to occur. This "priming" appears achievable with cyclopamine, but not IPI-926, and is cell-line dependent. Additionally, IPI-926 activity was evaluated in a murine tumor xenograft model and a pharmacokinetic/pharmacodynamic relationship was examined to assess for in vivo evidence of Hh pathway hyper-responsiveness. Plasma concentrations of IPI-926 correlated with the degree and duration of Hh pathway suppression, and pathway activity did not exceed baseline levels out to 96 hours post dose. The overall findings suggest that IPI-926 possesses

  11. Particulate matter in cigarette smoke increases ciliary axoneme beating through mechanical stimulation. (United States)

    Navarrette, Chelsea R; Sisson, Joseph H; Nance, Elizabeth; Allen-Gipson, Diane; Hanes, Justin; Wyatt, Todd A


    The lung's ability to trap and clear foreign particles via the mucociliary elevator is an important mechanism for protecting the lung against respirable irritants and microorganisms. Although cigarette smoke (CS) exposure and particulate inhalation are known to alter mucociliary clearance, little is known about how CS and nanoparticles (NPs) modify cilia beating at the cytoskeletal infrastructure, or axonemal, level. We used a cell-free model to introduce cigarette smoke extract (CSE) and NPs with variant size and surface chemistry to isolated axonemes and measured changes in ciliary motility. We hypothesized that CSE would alter cilia beating and that alterations in ciliary beat frequency (CBF) due to particulate matter would be size- and surface chemistry-dependent. Demembranated axonemes were isolated from ciliated bovine tracheas and exposed to adenosine triphosphate (ATP) to initiate motility. CBF was measured in response to 5% CSE, CSE filtrate, and carboxyl-modified (COOH), sulphate (SO(4))-modified (sulfonated), or PEG-coated polystyrene (PS) latex NPs ranging in size from 40 nm to 500 nm. CSE concentrations as low as 5% resulted in rapid, significant stimulation of CBF (pIntroduction of sulphate-modified PS beads ~300 nm in diameter resulted in a similar increase in CBF above baseline ATP levels. Uncharged, PEG-coated beads had no effect on CBF regardless of size. Similarly, COOH-coated particles less than 200 nm in diameter did not alter ciliary motility. However, COOH-coated PS particles larger than 300 nm increased CBF significantly and increased the number of motile points. These data show that NPs, including those found in CSE, mechanically stimulate axonemes in a size- and surface chemistry-dependent manner. Alterations in ciliary motility due to physicochemical properties of NPs may be important for inhalational lung injury and efficient drug delivery of respirable particles.



    José Romualdo Martínez-López; Erasmo Gutierrez-Ornelas; Miguel Angel Barrera-Silva; Rafael Retes-López


    A stochastic simulation model was constructed to determine the response of net primary production of buffelgrass (Cenchrus ciliaris L.) and its dry matter intake by cattle, in Marín, NL, México. Buffelgrass is very important for extensive livestock industry in arid and semiarid areas of northeastern Mexico. To evaluate the behavior of the model by comparing the model results with those reported in the literature was the objective in this experiment. Model simulates the monthly production of...

  13. Loss and gain of cone types in vertebrate ciliary photoreceptor evolution. (United States)

    Musser, Jacob M; Arendt, Detlev


    Ciliary photoreceptors are a diverse cell type family that comprises the rods and cones of the retina and other related cell types such as pineal photoreceptors. Ciliary photoreceptor evolution has been dynamic during vertebrate evolution with numerous gains and losses of opsin and phototransduction genes, and changes in their expression. For example, early mammals lost all but two cone opsins, indicating loss of cone receptor types in response to nocturnal lifestyle. Our review focuses on the comparison of specifying transcription factors and cell type-specific transcriptome data in vertebrate retinae to build and test hypotheses on ciliary photoreceptor evolution. Regarding cones, recent data reveal that a combination of factors specific for long-wavelength sensitive opsin (Lws)- cones in non-mammalian vertebrates (Thrb and Rxrg) is found across all differentiating cone photoreceptors in mice. This suggests that mammalian ancestors lost all but one ancestral cone type, the Lws-cone. We test this hypothesis by a correlation analysis of cone transcriptomes in mouse and chick, and find that, indeed, transcriptomes of all mouse cones are most highly correlated to avian Lws-cones. These findings underscore the importance of specifying transcription factors in tracking cell type evolution, and shed new light on the mechanisms of cell type loss and gain in retina evolution. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Comparative responses of the Savanna grasses Cenchrus ciliaris and Themeda triandra to defoliation. (United States)

    Hodgkinson, K C; Ludlow, M M; Mott, J J; Baruch, Z


    Two perennial tussock grasses of savannas were compared in a glasshouse study to determine why they differed in their ability to withstand frequent, heavy grazing; Cenchrus ciliaris is tolerant and Themeda triandra is intolerant of heavy grazing. Frequent defoliation at weekly intervals for six weeks reduced shoot biomass production over a subsequent 42 day regrowth period compared with previously undefoliated plants (infrequent) in T. triandra, but not in C. ciliaris. Leaf area of T. triandra expanded rapidly following defoliation but high initial relative growth rates of shoots were not sustained after 14 days of regrowth because of reducing light utilising efficiency of leaves. Frequently defoliated plants were slower in rate of leaf area expansion and this was associated with reduced photosynthetic capacity of newly formed leaves, lower allocation of photosynthate to leaves but not lower tiller numbers. T. triandra appears well adapted to a regime where defoliation is sufficiently infrequent to allow carbon to be fixed to replace that used in initial leaf area expansion. In contrast, C. ciliaris is better adapted to frequent defoliation than is T. triandra, because horizontally orientated nodal tillers are produced below the defoliation level. This morphological adaptation resulted in a 10-fold higher leaf area remaining after defoliation compared with similarly defoliated T. triandra, which together with the maintenance of moderate levels of light utilising efficiency, contributed to the higher leaf area and shoot weight throughout the regrowth period.

  15. Long-term clearance from small airways in subjects with ciliary dysfunction

    Directory of Open Access Journals (Sweden)

    Hjelte Lena


    Full Text Available Abstract The objective of this study was to investigate if long-term clearance from small airways is dependent on normal ciliary function. Six young adults with primary ciliary dyskinesia (PCD inhaled 111 Indium labelled Teflon particles of 4.2 μm geometric and 6.2 μm aerodynamic diameter with an extremely slow inhalation flow, 0.05 L/s. The inhalation method deposits particles mainly in the small conducting airways. Lung retention was measured immediately after inhalation and at four occasions up to 21 days after inhalation. Results were compared with data from ten healthy controls. For additional comparison three of the PCD subjects also inhaled the test particles with normal inhalation flow, 0.5 L/s, providing a more central deposition. The lung retention at 24 h in % of lung deposition (Ret24 was higher (p 24 with slow inhalation flow was 73.9 ± 1.9 % compared to 68.9 ± 7.5 % with normal inhalation flow in the three PCD subjects exposed twice. During day 7–21 the three PCD subjects exposed twice cleared 9 % with normal flow, probably representing predominantly alveolar clearance, compared to 19 % with slow inhalation flow, probably representing mainly small airway clearance. This study shows that despite ciliary dysfunction, clearance continues in the small airways beyond 24 h. There are apparently additional clearance mechanisms present in the small airways.

  16. Palladium-103 plaque radiation therapy for ciliary body melanoma through a functioning glaucoma filtering bleb. (United States)

    Pathan, Arif H K; Barash, Alexander; Tena, Lawrence B; Finger, Paul T


    To provide a clinical description of the long-term outcome of a 103 Pd plaque-irradiated ciliary body melanoma with extrascleral extension while attempting to preserve a subadjacent glaucoma filtering bleb. A 75-year-old woman with pseudoexfoliative glaucoma for 17 years, 16 years status post argon laser trabeculoplasty, and 15 years status post trabeculectomy in the left eye, was diagnosed with an ipsilateral ciliary body melanoma with visible extrascleral extension. Treatment involved insertion of a 103 Pd radioactive plaque over the functioning trabeculectomy, with removal 7 days later. At plaque insertion, amniotic membrane grafts were used to cover the plaque and protect the filtering site. The tumor was successfully treated without clinical evidence of harm to the filtering bleb, with resultant stable intraocular pressure. However, the patient developed blebitis 1.5 years later. Though it resolved with topical antibiotic therapy, the bleb became less succulent. Two years postoperatively, she developed a spontaneous hyphema that resolved after one injection of transscleral bevacizumab 1.25 mg. Her tumor continually regressed in thickness. Without additional glaucoma surgery, her intraocular pressure remained well-controlled on topical medications for 6 years. Ciliary body melanoma with minimal extrascleral extension beneath a functioning filtering bleb can be treated using radioactive plaque therapy. In this case, we were able to achieve both tumor regression and glaucoma control by covering the plaque with an amniotic membrane graft.

  17. Asymmetric wavefront aberrations and pupillary shapes induced by electrical stimulation of ciliary nerve in cats measured with compact wavefront aberrometer.

    Directory of Open Access Journals (Sweden)

    Suguru Miyagawa

    Full Text Available To investigate the changes in the wavefront aberrations and pupillary shape in response to electrical stimulation of the branches of the ciliary nerves in cats. Seven eyes of seven cats were studied under general anesthesia. Trains of monophasic pulses (current, 0.1 to 1.0 mA; duration, 0.5 ms/phase; frequency, 5 to 40 Hz were applied to the lateral or medial branch of the short ciliary nerve near the posterior pole of the eye. A pair of electrodes was hooked onto one or both branch of the short ciliary nerve. The electrodes were placed about 5 mm from the scleral surface. The wavefront aberrations were recorded continuously for 2 seconds before, 8 seconds during, and for 20 seconds after the electrical stimulation. The pupillary images were simultaneously recorded during the stimulation period. Both the wavefront aberrations and the pupillary images were obtained 10 times/sec with a custom-built wavefront aberrometer. The maximum accommodative amplitude was 1.19 diopters (D produced by electrical stimulation of the short ciliary nerves. The latency of the accommodative changes was very short, and the accommodative level gradually increased up to 4 seconds and reached a plateau. When only one branch of the ciliary nerve was stimulated, the pupil dilated asymmetrically, and the oblique astigmatism and one of the asymmetrical wavefront terms was also altered. Our results showed that the wavefront aberrations and pupillary dilations can be measured simultaneously and serially with a compact wavefront aberrometer. The asymmetric pupil dilation and asymmetric changes of the wavefront aberrations suggest that each branch of the ciliary nerve innervates specific segments of the ciliary muscle and dilator muscle of the pupil.

  18. Mycobacterium lutetiense sp. nov., Mycobacterium montmartrense sp. nov. and Mycobacterium arcueilense sp. nov., members of a novel group of non-pigmented rapidly growing mycobacteria recovered from a water distribution system. (United States)

    Konjek, Julie; Souded, Sabiha; Guerardel, Yann; Trivelli, Xavier; Bernut, Audrey; Kremer, Laurent; Welte, Benedicte; Joyeux, Michel; Dubrou, Sylvie; Euzeby, Jean-Paul; Gaillard, Jean-Louis; Sapriel, Guillaume; Heym, Beate


    From our recent survey of non-pigmented rapidly growing mycobacteria in the Parisian water system, three groups of isolates (taxons 1-3) corresponding to possible novel species were selected for taxonomic study. The three taxa each formed creamy white, rough colonies, had an optimal growth temperature of 30 °C, hydrolyzed Tween 80, were catalase-positive at 22 °C and expressed arylsulfatase activity. All three were susceptible to amikacin, ciprofloxacin and tigecycline. The three taxa produced specific sets of mycolic acids, including one family that has never previously been described, as determined by thin layer chromatography and nuclear magnetic resonance. The partial rpoB sequences (723 bp) showed 4-6 % divergence from each other and more than 5 % differences from the most similar species. Partial 16S rRNA gene sequences showed 99 % identity within each species. The most similar sequences for 16S rRNA genes (98-99 % identity over 1444-1461 bp) were found in the Mycobacterium fortuitum group, Mycobacterium septicum and Mycobacterium farcinogenes. The three taxa formed a new clade (bootstrap value, 99 %) on trees reconstructed from concatenated partial 16S rRNA, hsp65 and rpoB sequences. The above results led us to propose three novel species for the three groups of isolates, namely Mycobacterium lutetiense sp. nov. [type strain 071T=ParisRGMnew_1T (CIP 110656T=DSM 46713T)], Mycobacterium montmartrense sp. nov. [type strain 196T=ParisRGMnew_2T (CIP 110655T=DSM 46714T)] and Mycobacteriu marcueilense sp. nov. [type strain of 269T=ParisRGMnew_3T (CIP 110654T=DSM 46715T)].

  19. Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity. (United States)

    Lambert, P D; Anderson, K D; Sleeman, M W; Wong, V; Tan, J; Hijarunguru, A; Corcoran, T L; Murray, J D; Thabet, K E; Yancopoulos, G D; Wiegand, S J


    Ciliary Neurotrophic Factor (CNTF) was first characterized as a trophic factor for motor neurons in the ciliary ganglion and spinal cord, leading to its evaluation in humans suffering from motor neuron disease. In these trials, CNTF caused unexpected and substantial weight loss, raising concerns that it might produce cachectic-like effects. Countering this possibility was the suggestion that CNTF was working via a leptin-like mechanism to cause weight loss, based on the findings that CNTF acts via receptors that are not only related to leptin receptors, but also similarly distributed within hypothalamic nuclei involved in feeding. However, although CNTF mimics the ability of leptin to cause fat loss in mice that are obese because of genetic deficiency of leptin (ob/ob mice), CNTF is also effective in diet-induced obesity models that are more representative of human obesity, and which are resistant to leptin. This discordance again raised the possibility that CNTF might be acting via nonleptin pathways, perhaps more analogous to those activated by cachectic cytokines. Arguing strongly against this possibility, we now show that CNTF can activate hypothalamic leptin-like pathways in diet-induced obesity models unresponsive to leptin, that CNTF improves prediabetic parameters in these models, and that CNTF acts very differently than the prototypical cachectic cytokine, IL-1. Further analyses of hypothalamic signaling reveals that CNTF can suppress food intake without triggering hunger signals or associated stress responses that are otherwise associated with food deprivation; thus, unlike forced dieting, cessation of CNTF treatment does not result in binge overeating and immediate rebound weight gain.

  20. Ahmed glaucoma valve implantation with tube insertion through the ciliary sulcus in pseudophakic/aphakic eyes. (United States)

    Eslami, Yadolla; Mohammadi, Massood; Fakhraie, Ghasem; Zarei, Reza; Moghimi, Sasan


    To report the efficacy and safety of Ahmed glaucoma valve (AGV) insertion into the ciliary sulcus in pseudophakic/aphakic patients. A chart review was done on patients with uncontrolled glaucoma, who underwent AGV implantation with tube inserted into the ciliary sulcus. Baseline intraocular pressure (IOP) and number of medications were compared with that of postoperative follow-up visits. Surgical success was defined as last IOP glaucoma control, and without loss of light perception. Postoperative complications were recorded. Twenty-three eyes of 23 patients were recruited with the mean follow-up of 9 months (range, 3 to 24 mo). The mean (SD) age of patients was 49.9 (16.9) years (range, 22 to 80 years). The mean (SD) IOP (mm Hg) was reduced from 37.9 (12.4) before surgery to 16.2 (3.6) at the last follow-up visit (P<0.001). The mean (SD) number of medications was reduced from 3.3 (0.9) preoperatively to 1 (1.1) at the last follow-up (P<0.001). Success rate was 18/23 (78.6%). Complications included endophthalmitis in 1 eye, tube exposure in 1 diabetic patient, and vitreous tube occlusion in 1 eye. No case of corneal decompensation or graft failure was seen during follow-up. Ciliary sulcus placement of the tube of AGV effectively reduces IOP and medication use in short term. It has the potential to lower corneal complications of anterior chamber tube insertion and avoids the need for pars plana vitrectomy and tube insertion in patients at higher risk of corneal decompensation.

  1. IFT20 modulates ciliary PDGFRα signaling by regulating the stability of Cbl E3 ubiquitin ligases

    DEFF Research Database (Denmark)

    Schmid, Fabian Marc; Schou, Kenneth Bødtker; Vilhelm, Martin Juel


    ciliogenesis, and ciliary localization of the receptor is required for its appropriate ligand-mediated activation by PDGF-AA. However, the mechanisms regulating sorting of PDGFRα and feedback inhibition of PDGFRα signaling at the cilium are unknown. Here, we provide evidence that intraflagellar transport...... protein 20 (IFT20) interacts with E3 ubiquitin ligases c-Cbl and Cbl-b and is required for Cbl-mediated ubiquitination and internalization of PDGFRα for feedback inhibition of receptor signaling. In wild-type cells treated with PDGF-AA, c-Cbl becomes enriched in the cilium, and the receptor...

  2. Mucous flow and ciliary activity in the trachea of rats exposed to pulmonary irritant gas

    Energy Technology Data Exchange (ETDEWEB)

    Dalhamm, T; Rhodin, J


    Tracheal mucous secretion was increased in rats exposed to 10 ppM SO/sub 2/, 6 hr/day for 10 weeks. Mucous transport was decreased from 13.5 to 5 mm/min although ciliary beat remained a constant 1320 beats/min. The mucous layer was 5 times as thick as the normal Histologically, cilia were generally unaffected whereas tracheal epithelium was irregular with deep crypts, and the lamina propria showed severe edema, fragmentation of collagen fibrils, and profuse vascularization with blood escaping perivascularly.

  3. Mutations in DZIP1L, which encodes a ciliary transition zone protein, cause autosomal recessive polycystic kidney disease (United States)

    Lu, Hao; Galeano, Maria C. Rondón; Ott, Elisabeth; Kaeslin, Geraldine; Kausalya, P. Jaya; Kramer, Carina; Ortiz-Brüchle, Nadina; Hilger, Nadescha; Metzis, Vicki; Hiersche, Milan; Tay, Shang Yew; Tunningley, Robert; Vij, Shubha; Courtney, Andrew D.; Whittle, Belinda; Wühl, Elke; Vester, Udo; Hartleben, Björn; Neuber, Steffen; Frank, Valeska; Little, Melissa H.; Epting, Daniel; Papathanasiou, Peter; Perkins, Andrew C.; Wright, Graham D.; Hunziker, Walter; Gee, Heon Yung; Otto, Edgar A.; Zerres, Klaus; Hildebrandt, Friedhelm; Roy, Sudipto; Wicking, Carol; Bergmann, Carsten


    Autosomal recessive polycystic kidney disease (ARPKD), usually considered to be a genetically homogeneous disease caused by mutations in PKHD1, has been associated with ciliary dysfunction. Here, we describe mutations in the DAZ interacting protein 1-like (DZIP1L) gene in patients with ARPKD, findings we have further validated by loss-of-function studies in mice and zebrafish. DZIP1L localizes to centrioles and at the distal end of basal bodies, and interacts with septin2, a protein implicated in maintenance of the periciliary diffusion barrier at the ciliary transition zone. Consistent with a defect in the diffusion barrier, we found that the ciliary membrane translocation of the PKD proteins, polycystin-1 and −2, is compromised in DZIP1L mutant cells. Together, these data provide the first conclusive evidence that ARPKD is not a homogeneous disorder, and establishes DZIP1L as a second gene involved in its pathogenesis. PMID:28530676

  4. Mutations in DZIP1L, which encodes a ciliary-transition-zone protein, cause autosomal recessive polycystic kidney disease. (United States)

    Lu, Hao; Galeano, Maria C Rondón; Ott, Elisabeth; Kaeslin, Geraldine; Kausalya, P Jaya; Kramer, Carina; Ortiz-Brüchle, Nadina; Hilger, Nadescha; Metzis, Vicki; Hiersche, Milan; Tay, Shang Yew; Tunningley, Robert; Vij, Shubha; Courtney, Andrew D; Whittle, Belinda; Wühl, Elke; Vester, Udo; Hartleben, Björn; Neuber, Steffen; Frank, Valeska; Little, Melissa H; Epting, Daniel; Papathanasiou, Peter; Perkins, Andrew C; Wright, Graham D; Hunziker, Walter; Gee, Heon Yung; Otto, Edgar A; Zerres, Klaus; Hildebrandt, Friedhelm; Roy, Sudipto; Wicking, Carol; Bergmann, Carsten


    Autosomal recessive polycystic kidney disease (ARPKD), usually considered to be a genetically homogeneous disease caused by mutations in PKHD1, has been associated with ciliary dysfunction. Here, we describe mutations in DZIP1L, which encodes DAZ interacting protein 1-like, in patients with ARPKD. We further validated these findings through loss-of-function studies in mice and zebrafish. DZIP1L localizes to centrioles and to the distal ends of basal bodies, and interacts with septin2, a protein implicated in maintenance of the periciliary diffusion barrier at the ciliary transition zone. In agreement with a defect in the diffusion barrier, we found that the ciliary-membrane translocation of the PKD proteins polycystin-1 and polycystin-2 is compromised in DZIP1L-mutant cells. Together, these data provide what is, to our knowledge, the first conclusive evidence that ARPKD is not a homogeneous disorder and further establish DZIP1L as a second gene involved in ARPKD pathogenesis.

  5. Surgical treatment of iris and ciliary body melanoma: follow-up of a 25-year series of patients

    DEFF Research Database (Denmark)

    Klauber, Stefan; Jensen, Peter K; Prause, Jan U


    Purpose: To evaluate outcome of surgical resection of iris and irido-ciliary melanomas. Method: Retrospective analysis of all cases treated in Denmark 1975-1999 with clinical follow-up in 2002 and death certificate analysis in 2008. A quality of life questionnaire was completed at follow-up. Resu......Purpose: To evaluate outcome of surgical resection of iris and irido-ciliary melanomas. Method: Retrospective analysis of all cases treated in Denmark 1975-1999 with clinical follow-up in 2002 and death certificate analysis in 2008. A quality of life questionnaire was completed at follow...... time. However, none had changed job as a consequence of the surgical treatment. Only two patients were emotionally affected by the diagnosis of iris melanoma. Conclusion: Resection of small iris and irido-ciliary melanomas is a safe and efficient procedure, provided that strict diagnostic and surgical...

  6. Alteration of sodium, potassium-adenosine triphosphatase activity in rabbit ciliary processes by cyclic adenosine monophosphate-dependent protein kinase

    International Nuclear Information System (INIS)

    Delamere, N.A.; Socci, R.R.; King, K.L.


    The response of sodium, potassium-adenosine triphosphatase (Na,K-ATPase) to cyclic adenosine monophosphate (cAMP)-dependent protein kinase was examined in membranes obtained from rabbit iris-ciliary body. In the presence of the protein kinase together with 10(-5) M cAMP, Na,K-ATPase activity was reduced. No change in Na,K-ATPase activity was detected in response to the protein kinase without added cAMP. Likewise cAMP alone did not alter Na,K-ATPase activity. Reduction of Na,K-ATPase activity was also observed in the presence of the cAMP-dependent protein kinase catalytic subunit. The response of the enzyme to the kinase catalytic subunit was also examined in membranes obtained from rabbit ciliary processes. In the presence of 8 micrograms/ml of the catalytic subunit, ciliary process Na,K-ATPase activity was reduced by more than 50%. To examine whether other ATPases were suppressed by the protein kinase, calcium-stimulated ATPase activity was examined; its activity was stimulated by the catalytic subunit. To test whether the response of the ciliary process Na,K-ATPase is unique, experiments were also performed using membrane preparations from rabbit lens epithelium or rabbit kidney; the catalytic subunit significantly reduced the activity of Na,K-ATPase from the kidney but not the lens. These Na,K-ATPase studies suggest that in the iris-ciliary body, cAMP may alter sodium pump activity. In parallel 86Rb uptake studies, we observed that ouabain-inhibitable potassium uptake by intact pieces of iris-ciliary body was reduced by exogenous dibutryl cAMP or by forskolin

  7. Diagnosis of primary ciliary dyskinesia: potential options for resource-limited countries

    Directory of Open Access Journals (Sweden)

    Nisreen Rumman


    Full Text Available Primary ciliary dyskinesia is a genetic disease of ciliary function leading to chronic upper and lower respiratory tract symptoms. The diagnosis is frequently overlooked because the symptoms are nonspecific and the knowledge about the disease in the primary care setting is poor. Additionally, none of the available tests is accurate enough to be used in isolation. These tests are expensive, and need sophisticated equipment and expertise to analyse and interpret results; diagnosis is therefore only available at highly specialised centres. The diagnosis is particularly challenging in countries with limited resources due to the lack of such costly equipment and expertise. In this review, we discuss the importance of early and accurate diagnosis especially for countries where the disease is clinically prevalent but diagnostic tests are lacking. We review the diagnostic tests available in specialised centres (nasal nitric oxide, high-speed video microscopy, transmission electron microscopy, immunofluorescence and genetics. We then consider modifications that might be considered in less well-resourced countries whilst maintaining acceptable accuracy.

  8. C2 Domains as Protein-Protein Interaction Modules in the Ciliary Transition Zone

    Directory of Open Access Journals (Sweden)

    Kim Remans


    Full Text Available RPGR-interacting protein 1 (RPGRIP1 is mutated in the eye disease Leber congenital amaurosis (LCA and its structural homolog, RPGRIP1-like (RPGRIP1L, is mutated in many different ciliopathies. Both are multidomain proteins that are predicted to interact with retinitis pigmentosa G-protein regulator (RPGR. RPGR is mutated in X-linked retinitis pigmentosa and is located in photoreceptors and primary cilia. We solved the crystal structure of the complex between the RPGR-interacting domain (RID of RPGRIP1 and RPGR and demonstrate that RPGRIP1L binds to RPGR similarly. RPGRIP1 binding to RPGR affects the interaction with PDEδ, the cargo shuttling factor for prenylated ciliary proteins. RPGRIP1-RID is a C2 domain with a canonical β sandwich structure that does not bind Ca2+ and/or phospholipids and thus constitutes a unique type of protein-protein interaction module. Judging from the large number of C2 domains in most of the ciliary transition zone proteins identified thus far, the structure presented here seems to constitute a cilia-specific module that is present in multiprotein transition zone complexes.

  9. Genotypic variation in response to salinity in a new sexual germplasm of Cenchrus ciliaris L. (United States)

    Quiroga, Mariana; Tommasino, Exequiel; Griffa, Sabrina; Ribotta, Andrea; Colomba, Eliana López; Carloni, Edgardo; Grunberg, Karina


    As part of a breeding program for new salt-tolerant sexual genotypes of Cenchrus ciliaris L., here we evaluated the salt-stress response of two new sexual hybrids, obtained by controlled crosses, at seedling and germination stages. A seedling hydroponic experiment with 300 mM NaCl was performed and physiological variables and growth components were evaluated. While salt-treated sexual material did not show a decrease in productivity with respect to control plants, a differential response in some physiological characteristics was observed. Sexual hybrid 1-9-1 did not suffer oxidative damage and its proline content did not differ from that of control treatment. By contrast, sexual hybrid 1-7-11 suffered oxidative damage and accumulated proline, maintaining its growth under saline stress. At the germination stage, sexual hybrid 1-9-1 presented the highest Germination Rate Index at the maximum NaCl concentration assayed, suggesting an ecological advantage in this genotype. These new sexual resources are promising maternal parental with differential response to salt and could be incorporated in a breeding program of C. ciliaris in the search of new genotypes tolerant to salinity. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Posterior Ciliary Artery Occlusion Caused by Hyaluronic Acid Injections Into the Forehead: A Case Report. (United States)

    Hu, Xiu Zhuo; Hu, Jun Yan; Wu, Peng Sen; Yu, Sheng Bo; Kikkawa, Don O; Lu, Wei


    Although cosmetic facial soft tissue fillers are generally safe and effective, improper injections can lead to devastating and irreversible consequences. We represent the first known case of posterior ciliary artery occlusion caused by hyaluronic acid. A 41-year-old female presented with right visual loss 7 hours after receiving cosmetic hyaluronic acid injections into her forehead. Examination revealed no light perception in the right eye and multiple dark ischemic area of injection over the forehead and nose. The right fundus revealed a pink retina with optic nerve edema. Fluorescein angiogram showed several filling defects in the choroidal circulation and late hyperfluorescence in the choroid. A right posterior ciliary artery occlusion and embolic occlusion of facial artery braches was diagnosed. With hyaluronidase injection, hyperbaric oxygen therapy, oral aspirin, oral acetazolamide and dexamethasone venotransfuse treatment, the patient's forehead and nasal skin improved and vision recovered to hand movements. With proper technique, vascular occlusion is rare following facial filler injection. Vision consequences can be severe if filler emboli enter the ocular circulation. Physicians should be aware of this potential side effect, recognize its presentation, and be knowledgeable of effective management.

  11. Convergent evolution of RFX transcription factors and ciliary genes predated the origin of metazoans

    Directory of Open Access Journals (Sweden)

    Chen Nansheng


    Full Text Available Abstract Background Intraflagellar transport (IFT genes, which are critical for the development and function of cilia and flagella in metazoans, are tightly regulated by the Regulatory Factor X (RFX transcription factors (TFs. However, how and when their evolutionary relationship was established remains unknown. Results We have identified evidence suggesting that RFX TFs and IFT genes evolved independently and their evolution converged before the first appearance of metazoans. Both ciliary genes and RFX TFs exist in all metazoans as well as some unicellular eukaryotes. However, while RFX TFs and IFT genes are found simultaneously in all sequenced metazoan genomes, RFX TFs do not co-exist with IFT genes in most pre-metazoans and thus do not regulate them in these organisms. For example, neither the budding yeast nor the fission yeast possesses cilia although both have well-defined RFX TFs. Conversely, most unicellular eukaryotes, including the green alga Chlamydomonas reinhardtii, have typical cilia and well conserved IFT genes but lack RFX TFs. Outside of metazoans, RFX TFs and IFT genes co-exist only in choanoflagellates including M. brevicollis, and only one fungus Allomyces macrogynus of the 51 sequenced fungus genomes. M. brevicollis has two putative RFX genes and a full complement of ciliary genes. Conclusions The evolution of RFX TFs and IFT genes were independent in pre-metazoans. We propose that their convergence in evolution, or the acquired transcriptional regulation of IFT genes by RFX TFs, played a pivotal role in the establishment of metazoan.

  12. Ciliary metachronal wave propagation on the compliant surface of Paramecium cells. (United States)

    Narematsu, Naoki; Quek, Raymond; Chiam, Keng-Hwee; Iwadate, Yoshiaki


    Ciliary movements in protozoa exhibit metachronal wave-like coordination, in which a constant phase difference is maintained between adjacent cilia. It is at present generally thought that metachronal waves require hydrodynamic coupling between adjacent cilia and the extracellular fluid. To test this hypothesis, we aspirated a Paramecium cell using a micropipette which completely sealed the surface of the cell such that no fluid could pass through the micropipette. Thus, the anterior and the posterior regions of the cell were hydrodynamically decoupled. Nevertheless, we still observed that metachronal waves continued to propagate from the anterior to the posterior ends of the cell, suggesting that in addition to hydrodynamic coupling, there are other mechanisms that can also transmit the metachronal waves. Such transmission was also observed in computational modeling where the fluid was fully decoupled between two partitions of a beating ciliary array. We also imposed cyclic stretching on the surface of live Paramecium cells and found that metachronal waves persisted in the presence of cyclic stretching. This demonstrated that, in addition to hydrodynamic coupling, a compliant substrate can also play a critical role in mediating the propagation of metachronal waves. © 2015 Wiley Periodicals, Inc.

  13. Primary ciliary dyskinesia-causing mutations in Amish and Mennonite communities. (United States)

    Ferkol, Thomas W; Puffenberger, Erik G; Lie, Hauw; Helms, Cynthia; Strauss, Kevin A; Bowcock, Anne; Carson, John L; Hazucha, Milan; Morton, D Holmes; Patel, Anand C; Leigh, Margaret W; Knowles, Michael R; Zariwala, Maimoona A


    To determine whether individuals with primary ciliary dyskinesia (PCD) from unrelated Amish and Mennonite families harbor a single and unique founder mutation. Subjects from Amish and Mennonite communities in several states were enrolled in the study. All subjects were clinically characterized, and nasal nitric oxide levels were measured. Nasal epithelial scrapings were collected from several subjects for ciliary ultrastructural analyses. DNA was isolated from patients with PCD and their unaffected first- and second-degree relatives. Genome-wide homozygosity mapping, linkage analyses, targeted mutation analyses, and exome sequencing were performed. All subjects from Old-Order Amish communities from Pennsylvania were homozygous for a nonsense mutant DNAH5 allele, c.4348C>T (p.Q1450X). Two affected siblings from an unrelated Mennonite family in Arkansas were homozygous for the same nonsense DNAH5 mutation. Children with PCD from an Amish family from Wisconsin had biallelic DNAH5 mutations, c.4348C>T (p.Q1450X) and c.10815delT (p.P3606HfsX23), and mutations in other genes associated with PCD were also identified in this community. The Amish and Mennonite subjects from geographically dispersed and socially isolated communities had the same founder DNAH5 mutation, owing to the common heritage of these populations. However, disease-causing mutations in other PCD-associated genes were also found in affected individuals in these communities, illustrating the genetic heterogeneity in this consanguineous population. Copyright © 2013 Mosby, Inc. All rights reserved.

  14. Central Retinal and Posterior Ciliary Artery Occlusion After Intralesional Injection of Sclerosant to Glabellar Subcutaneous Hemangioma

    International Nuclear Information System (INIS)

    Matsuo, Toshihiko; Fujiwara, Hiroyasu; Gobara, Hideo; Mimura, Hidefumi; Kanazawa, Susumu


    The aim of this study is to describe vision loss caused by central retinal artery and posterior ciliary artery occlusion as a consequence of sclerotherapy with a polidocanol injection to a glabellar hemangioma. An 18-year-old man underwent direct injection with a 23-gauge needle of 1 mL of a polidocanol-carbon dioxide emulsion into the glabellar subcutaneous hemangioma under ultrasound visualization of the needle tip by radiologists. He developed lid swelling the next day, and 3 days later at referral, the visual acuity in the left eye was no light perception. Funduscopy revealed central retinal artery occlusion and fluorescein angiography disclosed no perfusion at all in the left fundus, indicating concurrent posterior ciliary artery occlusion. The patient also showed mydriasis, blepharoptosis, and total external ophthalmoplegia on the left side. Magnetic resonance imaging demonstrated the swollen medial rectus muscle. In a month, blepharoptosis and ophthalmoplegia resolved but the visual acuity remained no light perception. Sclerosing therapy for facial hemangioma may develop a severe complication such as permanent visual loss.

  15. [3H]acetylcholine synthesis in cultured ciliary ganglion neurons: effects of myotube membranes

    International Nuclear Information System (INIS)

    Gray, D.B.; Tuttle, J.B.


    Avian ciliary ganglion neurons in cell culture were examined for the capacity to synthesize acetylcholine (ACh) from the exogenously supplied precursor, choline. Relevant kinetic parameters of the ACh synthetic system in cultured neurons were found to be virtually the same as those of the ganglionic terminals in the intact iris. Neurons were cultured in the presence of and allowed to innervate pectoral muscle; this results in an capacity for ACh synthesis. In particular, the ability to increase ACh synthesis upon demand after stimulation is affected by interaction with the target. This effect is shown to be an acceleration of the maturation of the cultured neurons. Lysed and washed membrane remnants of the muscle target were able to duplicate, in part, this effect of live target tissue on neuronal transmitter metabolism. Culture medium conditioned by muscle, and by the membrane remnants of muscle, was without significant effect. Thus, substances secreted into the medium do not play a major role in this interaction. Neurons cultured with either muscle or muscle membrane remnants formed large, elongate structures on the target membrane surface. These were not seen in the absence of the target at the times examined. This morphological difference in terminal-like structures may parallel the developmental increases in size and vesicular content of ciliary ganglion nerve terminals in the chick iris, and may relate to the increased ACh synthetic activity. The results suggest that direct contact with an appropriate target membrane has a profound, retrograde influence upon neuronal metabolic and morphological maturation

  16. CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation

    DEFF Research Database (Denmark)

    Hjeij, Rim; Onoufriadis, Alexandros; Watson, Christopher M


    disorder of ciliary and flagellar dysmotility characterized by chronic upper and lower respiratory infections and defects in laterality. Here, by combined high-throughput mapping and sequencing, we identified CCDC151 loss-of-function mutations in five affected individuals from three independent families...

  17. X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3.

    NARCIS (Netherlands)

    Olcese, C.; Patel, M.P.; Shoemark, A.; Kiviluoto, S.; Legendre, M.; Williams, H.J.; Vaughan, C.K.; Hayward, J.; Goldenberg, A.; Emes, R.D.; Munye, M.M.; Dyer, L.; Cahill, T.; Bevillard, J.; Gehrig, C.; Guipponi, M.; Chantot, S.; Duquesnoy, P.; Thomas, L.; Jeanson, L.; Copin, B.; Tamalet, A.; Thauvin-Robinet, C.; Papon, J.F.; Garin, A.; Pin, I.; Vera, G.; Aurora, P.; Fassad, M.R.; Jenkins, L.; Boustred, C.; Cullup, T.; Dixon, M.; Onoufriadis, A.; Bush, A.; Chung, E.M.; Antonarakis, S.E.; Loebinger, M.R.; Wilson, R.; Armengot, M.; Escudier, E.; Hogg, C.; Amselem, S.; Sun, Z.; Bartoloni, L.; Blouin, J.L.; Mitchison, H.M.; Schmidts, M.; et al.,


    By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of

  18. CCDC151 Mutations Cause Primary Ciliary Dyskinesia by Disruption of the Outer Dynein Arm Docking Complex Formation

    NARCIS (Netherlands)

    Hjeij, R.; Onoufriadis, A.; Watson, C.M.; Slagle, C.E.; Klena, N.T.; Dougherty, G.W.; Kurkowiak, M.; Loges, N.T.; Diggle, C.P.; Morante, N.F.; Gabriel, G.C.; Lemke, K.L.; Li, Y.; Pennekamp, P.; Menchen, T.; Konert, F.; Marthin, J.K.; Mans, D.A.; Letteboer, S.J.F.; Werner, C.; Burgoyne, T.; Westermann, C.; Rutman, A.; Carr, I.M.; O'Callaghan, C.; Moya, E.; Chung, E.M.; Consortium, U.K.; Sheridan, E.; Nielsen, K.G.; Roepman, R.; Bartscherer, K.; Burdine, R.D.; Lo, C.W.; Omran, H.; Mitchison, H.M.


    A diverse family of cytoskeletal dynein motors powers various cellular transport systems, including axonemal dyneins generating the force for ciliary and flagellar beating essential to movement of extracellular fluids and of cells through fluid. Multisubunit outer dynein arm (ODA) motor complexes,

  19. Recombination within the apospory specific genomic region leads to the uncoupling of apomixis components in Cenchrus ciliaris. (United States)

    Conner, Joann A; Gunawan, Gunawati; Ozias-Akins, Peggy


    Apomixis enables the clonal propagation of maternal genotypes through seed. If apomixis could be harnessed via genetic engineering or introgression, it would have a major economic impact for agricultural crops. In the grass species Pennisetum squamulatum and Cenchrus ciliaris (syn. P. ciliare), apomixis is controlled by a single dominant "locus", the apospory-specific genomic region (ASGR). For P. squamulatum, 18 published sequenced characterized amplified region (SCAR) markers have been identified which always co-segregate with apospory. Six of these markers are conserved SCARs in the closely related species, C. ciliaris and co-segregate with the trait. A screen of progeny from a cross of sexual × apomictic C. ciliaris genotypes identified a plant, A8, retaining two of the six ASGR-linked SCAR markers. Additional and newly identified ASGR-linked markers were generated to help identify the extent of recombination within the ASGR. Based on analysis of missing markers, the A8 recombinant plant has lost a significant portion of the ASGR but continues to form aposporous embryo sacs. Seedlings produced from aposporous embryo sacs are 6× in ploidy level and hence the A8 recombinant does not express parthenogenesis. The recombinant A8 plant represents a step forward in reducing the complexity of the ASGR locus to determine the factor(s) required for aposporous embryo sac formation and documents the separation of expression of the two components of apomixis in C. ciliaris.

  20. Cardiopulmonary Exercise Testing in Fontan Patients With and Without Isomerism (Heterotaxy) as Compared to Patients With Primary Ciliary Dyskinesia and Subjects With Structurally Normal Hearts

    DEFF Research Database (Denmark)

    Loomba, Rohit S; Danduran, Michael; Nielsen, Kim G


    with and without isomerism. We have now compared these finding with those from patients with primary ciliary dyskinesia, as many patients with isomerism have ciliary dyskinesia. We identified patients having the Fontan circulation with and without isomerism who had undergone cardiopulmonary exercise testing......, comparing the findings from healthy individuals undergoing exercise, and a comparable number of individuals with primary ciliary dyskinesia but no congenital heart disease. We were able to include a total of 68 patients in our study, with 17 in each of the four groups. Cardiopulmonary exercise testing...

  1. Aerobic fitness in children and young adults with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Madsen, Astrid Hellerup; Green, Kent; Buchvald, Frederik


    BACKGROUND: Although aerobic fitness is regarded as an overall prognostic measure of morbidity and mortality, its evaluation in the chronic progressive sinopulmonary disease primary ciliary dyskinesia (PCD) has been infrequently and inconsistently reported. Here we assessed peak oxygen uptake (VO2...... multiple breath inert gas washout (N2 MBW) were assessed in a cross-sectional, single-occasion study of clinically stable children and young adults with PCD. We used a questionnaire including self-reported physical limitations in everyday life or in vigorous activities, and estimation of weekly hours...... patients. CONCLUSION: One-third of PCD patients exhibited substantially lower aerobic fitness than healthy subjects. Aerobic fitness correlated with FEV1, DLCO/VA and self-reported complaints of limitations in vigorous physical activity. These findings are most likely explained by PCD pulmonary disease...

  2. Induction of Functional 3D Ciliary Epithelium-Like Structure From Mouse Induced Pluripotent Stem Cells. (United States)

    Kinoshita, Hirofumi; Suzuma, Kiyoshi; Kaneko, Jun; Mandai, Michiko; Kitaoka, Takashi; Takahashi, Masayo


    To generate ciliary epithelium (CE) from mouse induced pluripotent stem (iPS) cells. Recently, a protocol for self-organizing optic cup morphogenesis in three-dimensional culture was reported, and it was suggested that ocular tissue derived from neural ectoderm could be differentiated. We demonstrated that a CE-like double-layered structure could be induced in simple culture by using a modified Eiraku differentiation protocol. Differentiation of a CE-like double-layered structure could be promoted by glycogen synthase kinase 3β (GSK-3β) inhibitor. Connexin43 and aquaporin1 were expressed in both thin layers, and induced CE-like cells expressed ciliary marker genes, such as cyclinD2, zic1, tgfb2, aldh1a3, wfdc1, otx1, BMP4, and BMP7. Increases in cytoplasmic and nuclear β-catenin in aggregates of the CE-like double-layered structure were confirmed by Western blot analysis. In addition, tankyrase inhibitor prevented the induction of the CE-like double-layered structure by GSK-3β inhibitor. Dye movement from pigmented cells to nonpigmented cells in the mouse iPS cell-derived CE-like structure was observed in a fluid movement experiment, consistent with the physiological function of CE in vivo. We could differentiate CE from mouse iPS cells in the present study. In the future, we hope that this CE-like complex will become useful as a graft for transplantation therapy in pathologic ocular hypotension due to CE dysfunction, and as a screening tool for the development of drugs for diseases associated with CE function.

  3. No evidence of cholesteatoma in untreated otitis media with effusion in children with primary ciliary dyskinesia. (United States)

    Ghedia, Reshma; Ahmed, Jahangir; Navaratnam, Annakan; Harcourt, Jonny


    Primary Ciliary Dyskinesia (PCD) describes a group of inherited disorders that result in abnormal ciliary motion leading to mucous stasis. Clinical features include almost universally otitis media with effusion (OME), particularly in infants. PCD patients provide us with a cohort of patients with OME that is not treated with ventilatory tube (VT) insertion as these have been shown to result in frequent complications including chronic otorrhoea, early extrusion and persistent perforation without significant improvement to hearing in the long term. This cohort was used to investigate whether children with PCD and OME not treated with VT were predisposed to cholesteatoma formation in the setting of a paediatric quaternary referral centre. A retrospective chart review was performed of all the children attending a multi-disciplinary PCD clinic at a national quaternary referral centre with a diagnosis of OME. We reviewed otoscopic findings, and audiometry and tympanometry results. We assessed the children in four groups: Watchful waiting, hearing aids, VT, and VT and hearing aids. One-hundred-and-one of 107 patients included in the study had a diagnosis of otitis media with effusion. No child with OME and PCD was diagnosed with a cholesteatoma during the follow up period. The only children who had insertion of a ventilatory tube were those who had the procedure prior to the formal diagnosis of PCD. We found a significant complication rate in the children with VT insertion. Hearing improved over time. The prevalence of retraction pockets in untreated OME was 1.72% (3 out of 174 ears). In children with PCD, OME is an almost universal finding in younger children, but not in adolescents. The study supports the current preference to avoid VT insertion in children with PCD as it confers a significantly higher rate of complications. No cases of cholesteatoma were found in this cohort of PCD children with OME managed without VTs. Crown Copyright © 2017. Published by Elsevier B

  4. Synergism between sulfur dioxide and carbon particles. Studies on adsorption and on ciliary movements in the rabbit trachea in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Dalhamn, T; Strandberg, L


    Various types of carbon were shown to absorb gaseous SO/sub 2/ (about 75% at equilibrium in one case), which was rapidly converted to sulfuric acid (30% of that adsorbed in one case). However, carbon did not act synergistically with SO/sub 2/ in reducing rabbit trachea ciliary beat; carbon had no effect by itself and had no additional effect when administered with SO/sub 2/. 74 to 134 ppM SO/sub 2/ reduced ciliary beat from 1265 to 1091 beats/min after 45 min, and 175 to 239 ppM SO/sub 2/ reduced it from 1200 to 891 beats/min after 45 min.

  5. Clinical value of measurement of pulmonary radioaerosol mucociliary clearance in the work up of primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Munkholm, Mathias; Nielsen, Kim Gjerum; Mortensen, Jann


    BACKGROUND: We aimed to evaluate and define the general clinical applicability and impact of pulmonary radioaerosol mucociliary clearance (PRMC) on the work up of patients suspected of having primary ciliary dyskinesia (PCD). In addition, we wanted to evaluate the accuracy of the reference values...... primarily to results from nasal ciliary function testing, to electron microscopic (EM) examination of the ultrastructure of the cilia, and to the final clinical diagnosis. RESULTS: Of the 239 patients, 27 ended up with a final clinical diagnosis of definitive PCD. No patients with a PRMC test...... of the entire lung. Its greatest strength is its ability to reject a suspected PCD diagnosis with great certainty. In our material, this accounted for 2/3 of referred patients. In addition, the test has a high rate of conclusive results. According to our analyses, reference equations on children would benefit...

  6. Long-term outcomes of ciliary sulcus versus capsular bag fixation of intraocular lenses in children: An ultrasound biomicroscopy study.

    Directory of Open Access Journals (Sweden)

    Yun-E Zhao

    Full Text Available To evaluate the long-term outcomes of ciliary sulcus versus capsular bag fixation of intraocular lenses (IOLs in children after pediatric cataract surgery.IOL was implanted in the ciliary sulcus in 21 eyes of 14 children, and in the capsular bag in 19 eyes of 12 children for the treatment of pediatric cataract in an institutional setting. Ultrasound biomicroscopy (UBM was performed. Main outcome measures included IOL decentration, IOL tilt, anterior chamber depth (ACD, angle-opening distance at 500 μm (AOD500, trabecular-iris angle (TIA, best-corrected visual acuity (BCVA, intraocular pressure (IOP, and incidence of postoperative complications.The mean follow-up period was 6.81 ± 1.82 years. Comparing to the capsular bag fixation group, the ciliary sulcus fixation group had higher vertical IOL decentration, horizontal IOL tilt, and vertical IOL tilt (p = 0.02, 0.01,0.01, respectively, higher incidence of iris-IOL contact and peripheral anterior synechia (p = 0.001, 0.03, respectively, smaller ACD, AOD500, and TIA (p = 0.02, 0.03, 0.04, respectively, higher mean IOP (17.10 ±6.06 mmHg vs.14.15± 4.74 mmHg, p = 0.01, and higher incidence of secondary glaucoma (28.57% vs. 10.53%, p = 0.007.There was no significant difference between the two groups with regard to the BCVA, refractive errors, incidence of myopic shift, nystagmus, strabismus, and visual axis opacity.Ciliary sulcus fixation of IOLs in pediatric eyes may increase IOL malposition and crowding of the anterior segment, and may associate with a higher risk of secondary glaucoma compared to capsular bag fixation of IOLs.

  7. Localization of a guanylyl cyclase to chemosensory cilia requires the novel ciliary MYND domain protein DAF-25.

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    Victor L Jensen


    Full Text Available In harsh conditions, Caenorhabditis elegans arrests development to enter a non-aging, resistant diapause state called the dauer larva. Olfactory sensation modulates the TGF-β and insulin signaling pathways to control this developmental decision. Four mutant alleles of daf-25 (abnormal DAuer Formation were isolated from screens for mutants exhibiting constitutive dauer formation and found to be defective in olfaction. The daf-25 dauer phenotype is suppressed by daf-10/IFT122 mutations (which disrupt ciliogenesis, but not by daf-6/PTCHD3 mutations (which prevent environmental exposure of sensory cilia, implying that DAF-25 functions in the cilia themselves. daf-25 encodes the C. elegans ortholog of mammalian Ankmy2, a MYND domain protein of unknown function. Disruption of DAF-25, which localizes to sensory cilia, produces no apparent cilia structure anomalies, as determined by light and electron microscopy. Hinting at its potential function, the dauer phenotype, epistatic order, and expression profile of daf-25 are similar to daf-11, which encodes a cilium-localized guanylyl cyclase. Indeed, we demonstrate that DAF-25 is required for proper DAF-11 ciliary localization. Furthermore, the functional interaction is evolutionarily conserved, as mouse Ankmy2 interacts with guanylyl cyclase GC1 from ciliary photoreceptors. The interaction may be specific because daf-25 mutants have normally-localized OSM-9/TRPV4, TAX-4/CNGA1, CHE-2/IFT80, CHE-11/IFT140, CHE-13/IFT57, BBS-8, OSM-5/IFT88, and XBX-1/D2LIC in the cilia. Intraflagellar transport (IFT (required to build cilia is not defective in daf-25 mutants, although the ciliary localization of DAF-25 itself is influenced in che-11 mutants, which are defective in retrograde IFT. In summary, we have discovered a novel ciliary protein that plays an important role in cGMP signaling by localizing a guanylyl cyclase to the sensory organelle.

  8. Sonic Hedgehog dependent phosphorylation by CK1α and GRK2 is required for ciliary accumulation and activation of smoothened.

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    Yongbin Chen


    Full Text Available Hedgehog (Hh signaling regulates embryonic development and adult tissue homeostasis through the GPCR-like protein Smoothened (Smo, but how vertebrate Smo is activated remains poorly understood. In Drosophila, Hh dependent phosphorylation activates Smo. Whether this is also the case in vertebrates is unclear, owing to the marked sequence divergence between vertebrate and Drosophila Smo (dSmo and the involvement of primary cilia in vertebrate Hh signaling. Here we demonstrate that mammalian Smo (mSmo is activated through multi-site phosphorylation of its carboxyl-terminal tail by CK1α and GRK2. Phosphorylation of mSmo induces its active conformation and simultaneously promotes its ciliary accumulation. We demonstrate that graded Hh signals induce increasing levels of mSmo phosphorylation that fine-tune its ciliary localization, conformation, and activity. We show that mSmo phosphorylation is induced by its agonists and oncogenic mutations but is blocked by its antagonist cyclopamine, and efficient mSmo phosphorylation depends on the kinesin-II ciliary motor. Furthermore, we provide evidence that Hh signaling recruits CK1α to initiate mSmo phosphorylation, and phosphorylation further increases the binding of CK1α and GRK2 to mSmo, forming a positive feedback loop that amplifies and/or sustains mSmo phosphorylation. Hence, despite divergence in their primary sequences and their subcellular trafficking, mSmo and dSmo employ analogous mechanisms for their activation.

  9. Short Communication: An apospory-specific genomic region is conserved between Buffelgrass (Cenchrus ciliaris L.) and Pennisetum squamulatum Fresen. (United States)

    Roche; Cong; Chen; Hanna; Gustine; Sherwood; Ozias-Akins


    Twelve molecular markers linked to pseudogamous apospory, a form of gametophytic apomixis, were previously isolated from Pennisetum squamulatum Fresen. No recombination between these markers was found in a segregating population of 397 individuals (Ozias-Akins et al. 1998, Proc. Natl Acad. Sci. USA, 95, 5127-5132). The objective of the present study was to test if these markers were also linked to the aposporous mode of reproduction in two small segregating populations of Cenchrus ciliaris (= Pennisetum ciliare (L.)Link), another apomictic grass species. Among 12 markers (sequence characterized amplified regions, SCARs), six were scored as dominant markers between aposporous and sexual C. ciliaris genotypes (presence/absence, respectively). Five were always linked to apospory and one showed a low level of recombination in 84 progenies. Restriction fragment length polymorphisms (RFLPs) were observed between sexual and apomictic phenotypes for three of the six remaining SCARs from P. squamulatum when used as probes. No recombination was observed in the F1 progenies. Preliminary data from megabase DNA analysis and sequencing in both species indicate that an apospory-specific genomic region (ASGR) is highly conserved between the two species. Although C. ciliaris has a smaller genome size to P. squamulatum, a higher copy number for markers linked to apospory found in the former may impair the progress of positional cloning of gene(s) for apomixis in this species.

  10. (/sup 3/H)ouabain localization of Na-K ATPase in the epithelium of rabbit ciliary body pars plicata

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    Usukura, J.; Fain, G.L.; Bok, D.


    The secretion of the aqueous humor has been proposed to occur as the result of active Na+ transport by a ouabain-sensitive Na-K ATPase. We have examined the localization of this enzyme in the epithelium of rabbit ciliary body pars plicata using (3H)ouabain autoradiography. Single ciliary processes were isolated and incubated in Ringer containing (3H)ouabain. Processes were then rapidly frozen, freezedried, sectioned and exposed for autoradiography. In the light microscope, silver grains were found predominantly over the nonpigmented epithelial cells. In the electron microscope, grains could be localized for the most part to the interdigitations of the nonpigmented cell basolateral membrane. Label could also be observed at a much lower density above other membranes and above the pigmented and nonpigmented cell cytoplasm. No label was found in sections of control tissue which had been incubated in (3H)ouabain with an excess of cold ouabain. To show that the (3H)ouabain had free access to all of the membrane surfaces within the epithelium, in parallel experiments we incubated isolated processes in horseradish peroxidase. Our experiments suggest that most of the active Na+ transport in ciliary body epithelium occurs across the basolateral membrane of nonpigmented cells into the posterior chamber. Furthermore, the placement of the Na-K ATPase within the narrow membrane infoldings of the interdigitations is consistent with a role for this enzyme in water transport and the production of the aqueous.

  11. OFD1, as a Ciliary Protein, Exhibits Neuroprotective Function in Photoreceptor Degeneration Models.

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    Juan Wang

    Full Text Available Ofd1 is a newly identified causative gene for Retinitis pigmentosa (RP, a photoreceptor degenerative disease. This study aimed to examine Ofd1 localization in retina and further to investigate its function in photoreceptor degeneration models. Ofd1 localization in rat retina was examined using immunofluorescence. N-methyl-N-nitrosourea (MNU-induced rats and Royal College of Surgeons (RCS rats were used as photoreceptor degeneration models. The expression pattern of Ofd1, other ciliary associated genes and Wnt signaling pathway genes were examined in rat models. Furthermore, pEGFP-Ofd1-CDS and pSUPER-Ofd1-shRNA were constructed to overexpress and knockdown the expression level in 661W and R28 cells. MNU was also used to induce cell death. Cilia formation was observed using immunocytochemistry (ICC. Reactive oxygen species (ROS were detected using the 2', 7'-Dichlorofluorescin diacetate (DCFH-DA assay. Apoptosis genes expression was examined using qRT-PCR, Western blotting and fluorescence-activated cell sorting (FACS. Ofd1 localized to outer segments of rat retina photoreceptors. Ofd1 and other ciliary proteins expression levels increased from the 1st and 4th postnatal weeks and decreased until the 6th week in the RCS rats, while their expression consistently decreased from the 1st and 7th day in the MNU rats. Moreover, Wnt signaling pathway proteins expression was significantly up-regulated in both rat models. Knockdown of Ofd1 expression resulted in a smaller population, shorter length of cell cilia, and lower cell viability. Ofd1 overexpression partially attenuated MNU toxic effects by reducing ROS levels and mitigating apoptosis. To the best of our knowledge, this is the first study demonstrating Ofd1 localization and its function in rat retina and in retinal degeneration rat models. Ofd1 plays a role in controlling photoreceptor cilium length and number. Importantly, it demonstrates a neuroprotective function by protecting the photoreceptor

  12. Recent invasion of buffel grass (Cenchrus ciliaris of a natural protected area from the southern Sonoran Desert Invasión reciente de zacate buffel (Cenchrus ciliaris en un área natural protegida del desierto sonorense

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    Erick De la Barrera


    Full Text Available The Centro Ecológico de Sonora is a natural protected area where the natural vegetation remained undisturbed at least until 1997. Since then, Cenchrus ciliaris has become a prominent element of the vegetation because of disturbance. Climate, soil properties, population structure and biological activity for C. ciliaris were studied to gain understanding of the ecological mechanisms that favored the invasion by this exotic grass. Mean air temperature and annual rainfall were 24.8°C and 302 mm. The soil was a loamy-sand that was poor in most nutrients, but particularly rich in phosphorus. Pennisetum ciliare was the most abundant species at the Centro Ecológico, representing over one third of total plant ground cover. Basal area for individual plants ranged from less than 1 cm² to almost 1 m². Living leaves per plant increased with precipitation, peaking at 199 leaves in March 2005, and no living leaves were found after 103 days without rain. The environmental conditions prevalent at Centro Ecológico are very favorable for C. ciliaris, whose establishment was apparently triggered by a major disturbance caused by the development of housing projects.El Centro Ecológico de Sonora es un área natural protegida donde la vegetación autóctona permaneció sin disturbios por lo menos hasta 1997. Desde entonces, Cenchrus ciliaris se ha convertido en un elemento prominente de la vegetación. Se estudiaron el clima, las propiedades del suelo, la estructura de la población y la actividad biológica de C. ciliaris, como una aproximación al entendimiento de los mecanismos ecológicos que favorecieron la invasión por este pasto exótico. La temperatura media del aire y la precipitación anual fueron de 24.8 °C y 302 mm. El suelo fue una arena limosa pobre en minerales, pero particularmente rica en fósforo. Cenchrus ciliaris fue la especie herbácea más abundante en el Centro Ecológico, representando más de un tercio de la cobertura vegetal. El

  13. Phylogenetic analysis of the Neks reveals early diversification of ciliary-cell cycle kinases.

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    Jeremy D K Parker


    Full Text Available NIMA-related kinases (Neks have been studied in diverse eukaryotes, including the fungus Aspergillus and the ciliate Tetrahymena. In the former, a single Nek plays an essential role in cell cycle regulation; in the latter, which has more than 30 Neks in its genome, multiple Neks regulate ciliary length. Mammalian genomes encode an intermediate number of Neks, several of which are reported to play roles in cell cycle regulation and/or localize to centrosomes. Previously, we reported that organisms with cilia typically have more Neks than organisms without cilia, but were unable to establish the evolutionary history of the gene family.We have performed a large-scale analysis of the Nek family using Bayesian techniques, including tests of alternate topologies. We find that the Nek family had already expanded in the last common ancestor of eukaryotes, a ciliated cell which likely expressed at least five Neks. We suggest that Neks played an important role in the common ancestor in regulating cilia, centrioles, and centrosomes with respect to mitotic entry, and that this role continues today in organisms with cilia. Organisms that lack cilia generally show a reduction in the number of Nek clades represented, sometimes associated with lineage specific expansion of a single clade, as has occurred in the plants.This is the first rigorous phylogenetic analysis of a kinase family across a broad array of phyla. Our findings provide a coherent framework for the study of Neks and their roles in coordinating cilia and cell cycle progression.

  14. The ciliary margin zone of the mammalian retina generates retinal ganglion cells (United States)

    Marcucci, Florencia; Murcia-Belmonte, Veronica; Coca, Yaiza; Ferreiro-Galve, Susana; Wang, Qing; Kuwajima, Takaaki; Khalid, Sania; Ross, M. Elizabeth; Herrera, Eloisa; Mason, Carol


    Summary The retina of lower vertebrates grows continuously by integrating new neurons generated from progenitors in the ciliary margin zone (CMZ). Whether the mammalian CMZ provides the neural retina with retinal cells is controversial. Live-imaging of embryonic retina expressing eGFP in the CMZ shows that cells migrate laterally from the CMZ to the neural retina where differentiated retinal ganglion cells (RGCs) reside. As Cyclin D2, a cell-cycle regulator, is enriched in ventral CMZ, we analyzed Cyclin D2−/− mice to test whether the CMZ is a source of retinal cells. Neurogenesis is diminished in Cyclin D2 mutants, leading to a reduction of RGCs in the ventral retina. In line with these findings, in the albino retina, the decreased production of ipsilateral RGCs is correlated with fewer Cyclin D2+ cells. Together, these results implicate the mammalian CMZ as a neurogenic site that produces RGCs and whose proper generation depends on Cyclin D2 activity. PMID:28009286

  15. Neural stem cells in the adult ciliary epithelium express GFAP and are regulated by Wnt signaling

    International Nuclear Information System (INIS)

    Das, Ani V.; Zhao Xing; James, Jackson; Kim, Min; Cowan, Kenneth H.; Ahmad, Iqbal


    The identification of neural stem cells with retinal potential in the ciliary epithelium (CE) of the adult mammals is of considerable interest because of their potential for replacing or rescuing degenerating retinal neurons in disease or injury. The evaluation of such a potential requires characterization of these cells with regard to their phenotypic properties, potential, and regulatory mechanisms. Here, we demonstrate that rat CE stem cells/progenitors in neurosphere culture display astrocytic nature in terms of expressing glial intermediate neurofilament protein, GFAP. The GFAP-expressing CE stem cells/progenitors form neurospheres in proliferating conditions and generate neurons when shifted to differentiating conditions. These cells express components of the canonical Wnt pathway and its activation promotes their proliferation. Furthermore, we demonstrate that the activation of the canonical Wnt pathway influences neuronal differentiation of CE stem cells/progenitors in a context dependent manner. Our observations suggest that CE stem cells/progenitors share phenotypic properties and regulatory mechanism(s) with neural stem cells elsewhere in the adult CNS

  16. Intraocular gene transfer of ciliary neurotrophic factor rescues photoreceptor degeneration in RCS rats. (United States)

    Huang, Shun-Ping; Lin, Po-Kang; Liu, Jorn-Hon; Khor, Chin-Ni; Lee, Yih-Jing


    Ciliary neurotrophic factor (CNTF) is known as an important factor in the regulation of retinal cell growth. We used both recombinant CNTF and an adenovirus carrying the CNTF gene to regulate retinal photoreceptor expression in a retinal degenerative animal, Royal College of Surgeons (RCS) rats. Cells in the outer nuclear layer of the retinae from recombinant-CNTF-treated, adenoviral-CNTF-treated, saline-operated, and contralateral untreated preparations were examined for those exhibiting CNTF photoreceptor protective effects. Cell apoptosis in the outer nuclear layer of the retinae was also detected. It was found that CNTF had a potent effect on delaying the photoreceptor degeneration process in RCS rats. Furthermore, adenovirus CNTF gene transfer was proven to be better at rescuing photoreceptors than that when using recombinant CNTF, since adenoviral CNTF prolonged the photoreceptor protection effect. The function of the photoreceptors was also examined by taking electroretinograms of different animals. Adenoviral-CNTF-treated eyes showed better retinal function than did the contralateral control eyes. This study indicates that adenoviral CNTF effectively rescues degenerating photoreceptors in RCS rats. Copyright 2004 National Science Council, ROC and S. Karger AG, Basel

  17. Reduced anaerobic and aerobic performance in children with primary ciliary dyskinesia. (United States)

    Simsek, Senem; Inal-Ince, Deniz; Cakmak, Aslihan; Emiralioglu, Nagehan; Calik-Kutukcu, Ebru; Saglam, Melda; Vardar-Yagli, Naciye; Ozcelik, Hayriye Ugur; Sonbahar-Ulu, Hazal; Bozdemir-Ozel, Cemile; Kiper, Nural; Arikan, Hulya


    Primary ciliary dyskinesia (PCD) restricts lifestyle and increases morbidity. The aim of the study was to investigate anaerobic and aerobic performance in children with PCD and their healthy counterparts. Thirty-one children with PCD and 29 age- and sex-matched healthy subjects were studied. Pulmonary function, hand grip strength (HGS), quadriceps strength (QMS), physical activity, anaerobic capacity (muscle power sprint test), and aerobic performance (modified shuttle walk test (MSWT)) were determined. Pulmonary function, HGS, QMS, mean anaerobic power (MAP), and MSWT distance in PCD were significantly lower than those of healthy subjects (p aerobic performance is impaired in PCD from the early stages. Age determines anaerobic performance. Gender is the determinant of aerobic performance. Whether skeletal muscle characteristics and sex-related changes in body composition affect anaerobic and aerobic capacity in PCD children warrants further study. What is Known: • Exercise performance is determined by anaerobic and aerobic power. • Few studies have shown that PCD patients have lower aerobic performance which is associated with impaired lung function. What is New: • The present research indicated that both anaerobic and aerobic exercise capacity determined using field testing is impaired in PCD from the early stages. • Anaerobic capacity was found to be independently associated with age in PCD. Higher aerobic performance is independently associated with male gender.

  18. Apparent X-linked primary ciliary dyskinesia associated with retinitis pigmentosa and a hearing loss. (United States)

    Krawczyński, Maciej R; Dmeńska, Hanna; Witt, Michał


    Three brothers, one 10-year-old and a pair of 14-year-old dizygotic twins--expressed the classical, early-onset retinitis pigmentosa (RP) with typical ophthalmoscopic findings, night blindness, visual field constricted to 10 degrees and flat ERG response. All three brothers were also diagnosed with primary ciliary dyskinesia (PCD) and had recurrent respiratory infections, chronic sinusitis and bronchiectasis. In all of them, resection of the middle lobe of the right lung was performed. A similar clinical picture of coexisting RP and PCD was noted in the brother of the probands' mother. All probands displayed situs solitus. Consistent with the X-linked mode of RP inheritance, there were also three obligatory female carriers of the disorder in this family: the mother of the affected boys, her mother and a daughter of her brother. In all of them, retinitis pigmentosa "sine pigmento" was found with milder but clinically significant symptoms (mild night blindness, visual field constricted to 30 degrees, and scotopic and photopic ERG responses reduced to 30-60%). No extraocular symptoms were detected in any of the heterozygous female carriers. This family presents an example of two rare phenomena: X-linked dominant retinitis pigmentosa (with milder expression in females) and a rare combination of RP with recurrent respiratory infections due to PCD.

  19. Exogenous ciliary neurotrophic factor (CNTF) reduces synaptic depression during repetitive stimulation. (United States)

    Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Priego, Mercedes; Obis, Teresa; Lanuza, Maria A; Besalduch, Nuria; Tomàs, Josep


    It has been shown that ciliary neurotrophic factor (CNTF) has trophic and maintenance effects on several types of peripheral and central neurons, glia, and cells outside the nervous system. Both CNTF and its receptor, CNTF-Rα, are expressed in the muscle. We use confocal immunocytochemistry to show that the trophic cytokine and its receptor are present in the pre- and post-synaptic sites of the neuromuscular junctions (NMJs). Applied CNTF (7.5-200 ng/ml, 60 min-3 h) does not acutely affect spontaneous potentials (size or frequency) or quantal content of the evoked acetylcholine release from post-natal (in weak or strong axonal inputs on dually innervated end plates or in the most mature singly innervated synapses at P6) or adult (P30) NMJ of Levator auris longus muscle of the mice. However, CNTF reduces roughly 50% the depression produced by repetitive stimulation (40 Hz, 2 min) on the adult NMJs. Our findings indicate that, unlike neurotrophins, exogenous CNTF does not acutely modulate transmitter release locally at the mammalian neuromuscular synapse but can protect mature end plates from activity-induced synaptic depression. © 2012 Peripheral Nerve Society.


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    José Romualdo Martínez-López


    Full Text Available A stochastic simulation model was constructed to determine the response of net primary production of buffelgrass (Cenchrus ciliaris L. and its dry matter intake by cattle, in Marín, NL, México. Buffelgrass is very important for extensive livestock industry in arid and semiarid areas of northeastern Mexico. To evaluate the behavior of the model by comparing the model results with those reported in the literature was the objective in this experiment. Model simulates the monthly production of dry matter of green grass, as well as its conversion to senescence and dry grass and eventually to mulch, depending on precipitation and temperature. Model also simulates consumption of green and dry grass for cattle. The stocking rate used in the model simulation was 2 hectares per animal unit. Annual production ranged from 4.5 to 10.2 t of dry matter per hectare with annual rainfall of 300 to 704 mm, respectively. Total annual intake required per animal unit was estimated at 3.6 ton. Simulated net primary production coincides with reports in the literature, so the model was evaluated successfully.

  1. The effects of the stem cell on ciliary regeneration of injured rabbit sinonasal epithelium. (United States)

    Kavuzlu, Ali; Tatar, Emel Çadallı; Karagöz, Tuğba; Pınarlı, Ferda Alpaslan; Tatar, İlkan; Bayır, Ömer; Korkmaz, Mehmet Hakan


    Defects in mucosal healing after sinonasal surgery cause infection, scar formation causing obstruction, relapse of the disease within a shorter period and revision surgery. The present study aimed to create a functional ciliated epithelium using a stem cell and stem cell sheet of adipose tissue origin and to show such regeneration ultra-structurally on experimentally injured rabbit nasal epithelium. This was an experimental animal study and basic research. A total of 18 white New Zealand rabbits were divided into three groups. The medial wall of the maxillary sinus of the subjects was peeled off bilaterally. No additional procedure was applied to the subjects in Group 1. In Group 2, adipose tissue-derived mesenchymal stem cell was implanted on the wound edges of the subjects. In Group 3, a stem cell sheet of three layers was laid onto the defect area. All subjects were killed after 3 weeks. The presence of the stem cell stained with bromo-deoxyuridine was assessed with a light microscope, whereas cilia density, ciliated orientation and cilia structure were evaluated with a scanning electron microscope. Ciliary densities in Group 2 and Group 3 were statistically superior compared to the control group (p stem cell increased the healing of the injured maxillary sinus mucosa of the rabbits in terms of cilia presence, density and morphology regardless of the implementation technique. Level of evidence NA.

  2. Central retinal and posterior ciliary artery occlusion after particle embolization of the external carotid artery system. (United States)

    Mames, R N; Snady-McCoy, L; Guy, J


    A 15-year-old boy underwent neuroradiologic embolization of the left internal maxillary artery with polyvinyl alcohol to stop traumatic epistaxis after failure of surgical clipping and nasal packing. Selective catheterization of the external carotid artery before embolization showed a faint choroidal blush. Although the procedure provided hemostasis, embolization to the central retinal artery and ciliary arteries resulted in loss of vision. The route of the emboli to the eye was via the anastomotic network of the lacrimal artery supplied by the external carotid artery system. Neuroradiologic embolization of the external carotid artery is an effective mode of therapy for dural-cavernous fistulas when fed by the external carotid artery system. Because the blood flow to the brain and eye is predominantly supplied by the internal carotid artery, embolization of the external carotid artery is considered relatively safe. The authors document the importance of recognition of the choroidal blush during selective external carotid artery angiography as a sign of collateral blood flow to the eye. Physicians and patients need to be aware of the risk of blindness as a complication of external carotid artery embolization when this sign is present.

  3. Porphyromonas pogonae identification from a soft tissue infection: The first human case. (United States)

    Kim, Bongyoung; Pai, Hyunjoo; Hwang, Kyu Tae; Lee, Yangsoon


    We report a first human case of Porphyromonas pogonae causing soft tissue infection in a patient with open fracture. Strong β-hemolytic, aerotolerant, and non-pigmented gram-negative coccobacilli which matched Porphyromonas pogonae by PCR for 16S rRNA genes were identified from the pus specimen. The clinical course of the patient improved with repeated surgical drainage and tigecycline administration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Functional short- and long-term effects of nasal CPAP with and without humidification on the ciliary function of the nasal respiratory epithelium. (United States)

    Sommer, J Ulrich; Kraus, Marius; Birk, Richard; Schultz, Johannes D; Hörmann, Karl; Stuck, Boris A


    Continuous positive airway pressure (CPAP) is the gold standard in the treatment of obstructive sleep apnea (OSA), but its impact on ciliary function is unclear to date. Furthermore, CPAP is associated with numerous side effects related to the nose and upper airway. Humidified CPAP is used to relieve these symptoms, but again, little is known regarding its effect on ciliary function of the nasal respiratory epithelium. In this prospective, randomized, crossover trial, 31 patients with OSA (AHI >15/h) were randomized to two treatment arms: nasal continuous positive airway pressure (nCPAP) with humidification or nCPAP without humidification for one night in each modality to assess short-term effects of ciliary beat frequency (CBF) and mucus transport time (MTT) and consecutively for 8 weeks in each modality to assess long-term effects in a crossover fashion. The baseline CBF was 4.8 ± 0.6 Hz, and baseline MTT was 540 ± 221 s. After one night of CPAP with and without humidification, ciliary function increased moderately yet with statistical significance (p humidification did not differ statistically significant. Regarding long-term effects of CPAP, a statistically significant increase in ciliary function above the baseline level and above the short-term level was shown without humidification (7.2 ± 0.4 Hz; 402 ± 176 s; p humidification (9.3 ± 0.7 Hz; 313 ± 95 s; p humidification, nCPAP has moderate effects on short-term ciliary function of the nasal respiratory epithelium. However, a significant increase in ciliary function-both in terms of an increased CBF and a decreased MTT-was detected after long-term use. The effect was more pronounced when humidification was used during nCPAP.

  5. An Automated Measurement of Ciliary Beating Frequency using a Combined Optical Flow and Peak Detection. (United States)

    Kim, Woojae; Han, Tae Hwa; Kim, Hyun Jun; Park, Man Young; Kim, Ku Sang; Park, Rae Woong


    The mucociliary transport system is a major defense mechanism of the respiratory tract. The performance of mucous transportation in the nasal cavity can be represented by a ciliary beating frequency (CBF). This study proposes a novel method to measure CBF by using optical flow. To obtain objective estimates of CBF from video images, an automated computer-based image processing technique is developed. This study proposes a new method based on optical flow for image processing and peak detection for signal processing. We compare the measuring accuracy of the method in various combinations of image processing (optical flow versus difference image) and signal processing (fast Fourier transform [FFT] vs. peak detection [PD]). The digital high-speed video method with a manual count of CBF in slow motion video play, is the gold-standard in CBF measurement. We obtained a total of fifty recorded ciliated sinonasal epithelium images to measure CBF from the Department of Otolaryngology. The ciliated sinonasal epithelium images were recorded at 50-100 frames per second using a charge coupled device camera with an inverted microscope at a magnification of ×1,000. The mean square errors and variance for each method were 1.24, 0.84 Hz; 11.8, 2.63 Hz; 3.22, 1.46 Hz; and 3.82, 1.53 Hz for optical flow (OF) + PD, OF + FFT, difference image [DI] + PD, and DI + FFT, respectively. Of the four methods, PD using optical flow showed the best performance for measuring the CBF of nasal mucosa. The proposed method was able to measure CBF more objectively and efficiently than what is currently possible.

  6. Evaluation of pulmonary disease using static lung volumes in primary ciliary dyskinesia. (United States)

    Pifferi, Massimo; Bush, Andrew; Pioggia, Giovanni; Caramella, Davide; Tartarisco, Gennaro; Di Cicco, Maria; Zangani, Marta; Chinellato, Iolanda; Maggi, Fabrizio; Tezza, Giovanna; Macchia, Pierantonio; Boner, Attilio


    In primary ciliary dyskinesia (PCD) lung damage is usually evaluated by high-resolution CT (HRCT). To evaluate whether HRCT abnormalities and Pseudomonas aeruginosa infection were better predicted by spirometry or plethysmography. A cross-sectional study performed in consecutive patients with PCD who underwent sputum culture, spirometry, plethysmography and HRCT within 48 h. Principal component analysis and soft computing were used for data evaluation. Fifty patients (26 children) were studied. P aeruginosa infection was found in 40% of the patients and bronchiectasis in 88%. There was a correlation between infection with P aeruginosa and extent of bronchiectasis (p=0.009; r =0.367) and air-trapping (p=0.03; r =0.315). Moreover, there was an association between infection with P aeruginosa and residual volume (RV) values >150% (p=0.04) and RV/total lung capacity (TLC) ratio >140% (p=0.001), but not between infection with P aeruginosa and forced expiratory volume in 1 s (FEV(1))<80%, or forced expiratory flow between 25% and 75% of forced vital capacity (FVC) (FEF(25-75%))<70% or FEV(1)/FVC<70% (<80% in children). Severity of the total lung impairment on chest HRCT directly correlated with RV when expressed as per cent predicted (p=0.003; r =0.423), and RV/TLC (p<0.001; r =0.513) or when expressed as z scores (p=0.002, r =0.451 and p<0.001, r =0.536 respectively). Principal component analysis on plethysmographic but not on spirometry data allowed recognition of different severities of focal air trapping, atelectasis and extent of bronchiectasis. Plethysmography better predicts HRCT abnormalities than spirometry. Whether it might be a useful test to define populations of patients with PCD who should or should not have HRCT scans requires further longitudinal studies.

  7. Clinical outcomes of Ahmed glaucoma valve in anterior chamber versus ciliary sulcus. (United States)

    Bayer, A; Önol, M


    PurposeTo evaluate the outcomes of Ahmed glaucoma valve (AGV) tube insertion through the anterior chamber angle (ACA) or through the ciliary sulcus (CS).Patients and methodsIn this case-control study, we retrospectively reviewed the charts of consecutive glaucoma patients who had undergone AGV implantation either through the ACA or the CS between March 2009 and December 2014. The main outcome measures were intraocular pressure (IOP), number of glaucoma medications prescribed, best corrected visual acuity (BCVA), glaucoma type, success rate, complications, and survival ratios. Statistical analysis was carried out using SPSS.ResultsThere were 68 eyes in the ACA group and 35 eyes in the CS group. There were no significant differences between the groups for age, sex, laterality, IOP, preoperative glaucoma medication number, BCVA or glaucoma type (P>0.05). The postoperative follow-up period was 27.2±16.5 months and 30.2±17.7 months for the ACA and the CS groups (P=0.28); IOP values were significantly reduced at the last visit to 16.4±7.2 mm Hg and 14.4±6.8 mm Hg. The difference in the last-visit IOP between the groups was not significant (P=0.06), but the IOP reduction ratio was higher in the CS group (P=0.03). There was no significant difference in the number of postoperative medications (P=0.18). Postoperative complications were similar, but the incidence of flat anterior chamber was higher in the ACA group (P=0.05).ConclusionsThe use of an AGV can control IOP in the majority of cases whether placed in the ACA or the CS. The IOP reduction ratio seemed to be higher in the CS group.

  8. In vitro assessment of TAT — Ciliary Neurotrophic Factor therapeutic potential for peripheral nerve regeneration

    International Nuclear Information System (INIS)

    Barbon, Silvia; Stocco, Elena; Negro, Alessandro; Dalzoppo, Daniele; Borgio, Luca; Rajendran, Senthilkumar; Grandi, Francesca; Porzionato, Andrea; Macchi, Veronica; De Caro, Raffaele


    In regenerative neurobiology, Ciliary Neurotrophic Factor (CNTF) is raising high interest as a multifunctional neurocytokine, playing a key role in the regeneration of injured peripheral nerves. Despite its promising trophic and regulatory activity, its clinical application is limited by the onset of severe side effects, due to the lack of efficient intracellular trafficking after administration. In this study, recombinant CNTF linked to the transactivator transduction domain (TAT) was investigated in vitro and found to be an optimized fusion protein which preserves neurotrophic activity, besides enhancing cellular uptake for therapeutic advantage. Moreover, a compelling protein delivery method was defined, in the future perspective of improving nerve regeneration strategies. Following determination of TAT-CNTF molecular weight and concentration, its specific effect on neural SH-SY5Y and PC12 cultures was assessed. Cell proliferation assay demonstrated that the fusion protein triggers PC12 cell growth within 6 h of stimulation. At the same time, the activation of signal transduction pathway and enhancement of cellular trafficking were found to be accomplished in both neural cell lines after specific treatment with TAT-CNTF. Finally, the recombinant growth factor was successfully loaded on oxidized polyvinyl alcohol (PVA) scaffolds, and more efficiently released when polymer oxidation rate increased. Taken together, our results highlight that the TAT domain addiction to the protein sequence preserves CNTF specific neurotrophic activity in vitro, besides improving cellular uptake. Moreover, oxidized PVA could represent an ideal biomaterial for the development of nerve conduits loaded with the fusion protein to be delivered to the site of nerve injury. - Highlights: • TAT-CNTF is an optimized fusion protein that preserves neurotrophic activity. • In neural cell lines, TAT-CNTF triggers the activation of signal transduction. • Fast cellular uptake of TAT-CNTF was

  9. In vitro assessment of TAT — Ciliary Neurotrophic Factor therapeutic potential for peripheral nerve regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Barbon, Silvia, E-mail: [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling (TES) ONLUS, Via De Sanctis 10, Caselle di Selvazzano Dentro, 35030 Padua (Italy); Stocco, Elena, E-mail: [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling (TES) ONLUS, Via De Sanctis 10, Caselle di Selvazzano Dentro, 35030 Padua (Italy); Negro, Alessandro, E-mail: [Department of Biomedical Sciences, University of Padova, Via Colombo 3, 35121 Padua (Italy); Dalzoppo, Daniele, E-mail: [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Borgio, Luca, E-mail: [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Rajendran, Senthilkumar, E-mail: [Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua (Italy); Grandi, Francesca, E-mail: [Department of Women' s and Children' s Health, Pediatric Surgery, University of Padua, Via Giustiniani 3, 35121 Padua (Italy); Porzionato, Andrea, E-mail: [Section of Human Anatomy, Department of Molecular Medicine, University of Padua, Via Gabelli 65, 35121 Padua (Italy); Macchi, Veronica, E-mail: [Section of Human Anatomy, Department of Molecular Medicine, University of Padua, Via Gabelli 65, 35121 Padua (Italy); De Caro, Raffaele, E-mail: [Section of Human Anatomy, Department of Molecular Medicine, University of Padua, Via Gabelli 65, 35121 Padua (Italy); and others


    In regenerative neurobiology, Ciliary Neurotrophic Factor (CNTF) is raising high interest as a multifunctional neurocytokine, playing a key role in the regeneration of injured peripheral nerves. Despite its promising trophic and regulatory activity, its clinical application is limited by the onset of severe side effects, due to the lack of efficient intracellular trafficking after administration. In this study, recombinant CNTF linked to the transactivator transduction domain (TAT) was investigated in vitro and found to be an optimized fusion protein which preserves neurotrophic activity, besides enhancing cellular uptake for therapeutic advantage. Moreover, a compelling protein delivery method was defined, in the future perspective of improving nerve regeneration strategies. Following determination of TAT-CNTF molecular weight and concentration, its specific effect on neural SH-SY5Y and PC12 cultures was assessed. Cell proliferation assay demonstrated that the fusion protein triggers PC12 cell growth within 6 h of stimulation. At the same time, the activation of signal transduction pathway and enhancement of cellular trafficking were found to be accomplished in both neural cell lines after specific treatment with TAT-CNTF. Finally, the recombinant growth factor was successfully loaded on oxidized polyvinyl alcohol (PVA) scaffolds, and more efficiently released when polymer oxidation rate increased. Taken together, our results highlight that the TAT domain addiction to the protein sequence preserves CNTF specific neurotrophic activity in vitro, besides improving cellular uptake. Moreover, oxidized PVA could represent an ideal biomaterial for the development of nerve conduits loaded with the fusion protein to be delivered to the site of nerve injury. - Highlights: • TAT-CNTF is an optimized fusion protein that preserves neurotrophic activity. • In neural cell lines, TAT-CNTF triggers the activation of signal transduction. • Fast cellular uptake of TAT-CNTF was

  10. The role of hair cells, cilia and ciliary motility in otolith formation in the zebrafish otic vesicle. (United States)

    Stooke-Vaughan, Georgina A; Huang, Peng; Hammond, Katherine L; Schier, Alexander F; Whitfield, Tanya T


    Otoliths are biomineralised structures required for the sensation of gravity, linear acceleration and sound in the zebrafish ear. Otolith precursor particles, initially distributed throughout the otic vesicle lumen, become tethered to the tips of hair cell kinocilia (tether cilia) at the otic vesicle poles, forming two otoliths. We have used high-speed video microscopy to investigate the role of cilia and ciliary motility in otolith formation. In wild-type ears, groups of motile cilia are present at the otic vesicle poles, surrounding the immotile tether cilia. A few motile cilia are also found on the medial wall, but most cilia (92-98%) in the otic vesicle are immotile. In mutants with defective cilia (iguana) or ciliary motility (lrrc50), otoliths are frequently ectopic, untethered or fused. Nevertheless, neither cilia nor ciliary motility are absolutely required for otolith tethering: a mutant that lacks cilia completely (MZovl) is still capable of tethering otoliths at the otic vesicle poles. In embryos with attenuated Notch signalling [mindbomb mutant or Su(H) morphant], supernumerary hair cells develop and otolith precursor particles bind to the tips of all kinocilia, or bind directly to the hair cells' apical surface if cilia are absent [MZovl injected with a Su(H)1+2 morpholino]. However, if the first hair cells are missing (atoh1b morphant), otolith formation is severely disrupted and delayed. Our data support a model in which hair cells produce an otolith precursor-binding factor, normally localised to tether cell kinocilia. We also show that embryonic movement plays a minor role in the formation of normal otoliths.


    Croft, Mary Ann; Mcdonald, Jared P.; James, Rebecca J.; Heatley, Gregg A.; Lin, Ting-Li; Lütjen-Drecoll, Elke; Kaufman, Paul L.


    Purpose To determine how surgically altering the normal relationship between the lens and the ciliary body in rhesus monkeys affects centripetal ciliary body and lens movement. Methods In 18 rhesus monkey eyes (aged 6–27 years), accommodation was induced before and after surgery by electrical stimulation of the Edinger-Westphal (E–W) nucleus. Accommodative amplitude was measured by coincidence refractometry. Goniovideography was performed before and after intra- and extra-capsular lens extraction (ICLE, ECLE) and anterior regional zonulolysis. Centripetal lens/capsule movements, centripetal ciliary process (CP) movements, and circumlental space were measured by computerized image analysis of the goniovideography images. Results Centripetal accommodative CP and capsule movement increased in velocity and amplitude post-ECLE compared to pre-ECLE regardless of age (n=5). The presence of the lens substance retarded capsule movement by ~21% in the young eyes and by ~62% in the older eyes. Post-ICLE compared to pre-ICLE centripetal accommodative CP movement was dampened in all eyes in which the anterior vitreous was disturbed (n=7), but not in eyes in which the anterior vitreous was left intact (n=2). Following anterior regional zonulolysis (n=4), lens position shifted toward the lysed quadrant during accommodation. Conclusions The presence of the lens substance, capsule zonular attachments, and Wiegers ligament may play a role in centripetal CP movement. The capsule is still capable of centripetal movement in the older eye (although at a reduced capacity) and may have the ability to produce ~6 diopters of accommodation in the presence of a normal young crystalline lens or a similar surrogate. PMID:18552393

  12. Growth, biomass production and photosynthesis of Cenchrus ciliaris L. under Acacia tortilis (Forssk.) Hayne based silvopastoral systems in semi arid tropics. (United States)

    Mishra, A K; Tiwari, H S; Bhatt, R K


    The growth, biomass production and photosynthesis of Cenchrus ciliaris was studied under the canopies of 17 yr old Acacia tortilis trees in semi arid tropical environment. On an average the full grown canopy of A. tortilis at the spacing of 4 x 4 m allowed 55% of total Photosynthetically Active Radiation (PAR) which in turn increased Relative Humidity (RH) and reduced under canopy temperature to -1.75 degrees C over the open air temperature. C. ciliaris attained higher height under the shade of A. tortilis. The tiller production and leaf area index decreased marginally under the shade of tree canopies as compared to the open grown grasses. C. ciliaris accumulated higher chlorophyll a and b under the shade of tree canopies indicating its shade adaptation potential. The assimilatory functions such as rate of photosynthesis, transpiration, stomatal conductance, photosynthetic water use efficiency (PN/TR) and carboxylation efficiency (PN/CINT) decreased under the tree canopies due to low availability of PAR. The total biomass production in term of fresh and dry weight decreased under the tree canopies. On average of 2 yr C. ciliaris had produced 12.78 t ha(-1) green and 3.72 -t ha(-1) dry biomass under the tree canopies of A. tortilis. The dry matter yield reduced to 38% under the tree canopies over the open grown grasses. The A. tortilis + C. ciliaris maintained higher soil moisture, organic carbon content and available N P K for sustainable biomass production for the longer period. The higher accumulation of crude protein, starch, sugar and nitrogen in leaves and stem of C. ciliaris indicates that this grass species also maintained its quality under A. tortilis based silvopastoral system. The photosynthesis and dry matter accumulation are closely associated with available PAR indicating that for sustainable production of this grass species in the silvopasture systems for longer period about 55% or more PAR is required.

  13. A case report of primary ciliary dyskinesia, laterality defects and developmental delay caused by the co-existence of a single gene and chromosome disorder.

    LENUS (Irish Health Repository)

    Casey, Jillian P


    Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterised by abnormal ciliary motion and impaired mucociliary clearance, leading to recurrent respiratory infections, sinusitis, otitis media and male infertility. Some patients also have laterality defects. We recently reported the identification of three disease-causing PCD genes in the Irish Traveller population; RSPH4A, DYX1C1 and CCNO. We have since assessed an additional Irish Traveller family with a complex phenotype involving PCD who did not have any of the previously identified PCD mutations.

  14. Lung structure and function similarities between primary ciliary dyskinesia and mild cystic fibrosis: a pilot study. (United States)

    Maglione, Marco; Montella, Silvia; Mollica, Carmine; Carnovale, Vincenzo; Iacotucci, Paola; De Gregorio, Fabiola; Tosco, Antonella; Cervasio, Mariarosaria; Raia, Valeria; Santamaria, Francesca


    Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are increasingly compared. There are no chest magnetic resonance imaging (MRI) comparative studies of PCD and CF. We assessed clinical, functional, microbiological and MRI findings in PCD and mild CF patients in order to evaluate different expression of lung disease. Twenty PCD (15.1 years) and 20 CF subjects with mild respiratory impairment (16 years, 70% with pancreatic insufficiency) underwent MRI, spirometry, and sputum cultures when clinically stable. MRI was scored using the modified Helbich system. PCD was diagnosed later than CF (9.9 versus 0.6 years, p = 0.03), despite earlier symptoms (0.1 versus 0.6 years, p = 0.02). In the year preceding the study, patients from both groups underwent two systemic antibiotic courses (p = 0.48). MRI total scores were 11.6 ± 0.7 and 9.1 ± 1 in PCD and CF, respectively. FEV 1 and FVC Z-scores were -1.75 (range, -4.6-0.7) and -0.6 (-3.9-1.8) in PCD, and -0.9 (range, -5.4-2.3) and -0.3 (-3.4-2.5) in CF, respectively. No difference was found between lung function or structure, despite a higher MRI subscore of collapse/consolidation in PCD versus CF (1.6 ± 0.1 and 0.6 ± 0.2, p < 0.001). These findings were confirmed after data-control for diagnostic delay. Pseudomonas aeruginosa and Staphylococcus aureus were more frequent in CF than in PCD (p = 0.05 and p = 0.003, respectively). MRI is a valuable radiation-free tool for comparative PCD and CF lung disease assessment. Patients with PCD may exhibit similar MRI and lung function changes as CF subjects with mild pulmonary disease. Delay in PCD diagnosis is unlikely the only determinant of similarities.

  15. Does the disruption of horizontal anterior ciliary vessels affect the blood-aqueous barrier function? (United States)

    Pan, Meihua; Yang, Mei; Xie, Renyi; Zhao, Zhimin; Huang, Xingxing


    To investigate the significance of the anterior ciliary vessels (ACVs) preservation during the conventional horizontal strabismus surgery. Patients (≥ 8 years) with horizontal strabismus were randomly allocated into group 1 (with ACV preservation) and group 2 (without ACV preservation). The surgical eyes in group 1 were further divided into group A (one rectus muscle operated) and group B (two rectus muscles operated). Similarly, eyes in group 2 were divided into group C (one rectus muscle operated) and group D (two rectus muscles operated). The success rate of ACV preservation was calculated. The anterior chamber flare measurements of each eye by laser flare photometry were recorded on the day prior to and after operation. The flare values between groups and between pre- and post-operation in each group were compared by one-way analysis of variance and a paired t-test respectively. In groups A and B, the success rate of ACV preservation was 82% (27/33) and 70% (28/40)respectively, and the flare values between pre- and post-operation showed no significant differences(4.378 ± 1.527, 4.544 ± 1.452, P = 0.526; 4.625 ± 1.090, 4.989 ± 1.468, P = 0.101 respectively). However, the postoperative values were significantly increased in group C and group D(4.661 ± 1.031, 5.039 ± 1.310, P = 0.025; 4.933 ± 1.691, 5.502 ± 1.430, P = 0.000 respectively). The postoperative flare readings of group D were significantly higher than group B, while group A and group C had no significant variation. ACV preservation probably has clinical significance in reducing the undesirable influence on the blood-aqueous barrier.

  16. [Endoscopically controlled optimization of trans-scleral suture fixation of posterior chamber lenses in the ciliary sulcus]. (United States)

    Althaus, C; Sundmacher, R


    Two technical difficulties have to be overcome in transscleral suture fixation of posterior chamber intraocular lenses (PCL) in the ciliary sulcus: first, exact needle penetration through the sulcus, and second, exact positioning of the PCL haptics in the sulcus. Incongruence of the two may lead to long-term complications by compression or even strangulation of ciliary processes. Intraocular endoscopy was used intraoperatively to visualize the site of needle penetration and the final location of the haptics in patients. It turned out that with our previously described standard techniques the precision was far less than anticipated. Thus, new technical ways had to be sought to improve the precision of positioning. In secondary implantation without perforating keratoplasty we achieved the best results when the needle was passed ab externo before opening the eye and before anterior vitrectomy, taking advantage of a precisely prepared sclerocorneal zone. Passing the needle ab externo in an already hypotonic eyeball gives much less precise results. In combination with perforating keratoplasty with an open-sky approach, needle penetration ab interno is reliable. Correct positioning of the PCL haptics is at least as difficult as correct needle penetration, a fact which up to now has mostly been ignored. In 33 consecutively operated eyes the technique of implantation and PCL design was varied under endoscopical control.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Control of ciliary motility by Ca2+: Integration of Ca2+-dependent functions and targets for Ca2+ action

    International Nuclear Information System (INIS)

    Evans, T.C.


    To identify functions that regulate Ca 2+ -induced ciliary reversal in Paramecium, mutants defective in terminating depolarization-induced backward swimming were selected. Six independent recessive mutations (k-shy) comprising two complementation groups, k-shyA and k-shyB, were identified. All mutants exhibited prolonged backward swimming in depolarizing solutions. Voltage clamp studies revealed that mutant Ca 2+ current amplitudes were reduced, but could be restored to wild type levels by EGTA injection. The recovery of the mutant Ca 2+ current from Ca 2+ -dependent inactivation, and the decay of the Ca 2+ -dependent K + and Ca 2+ -dependent Na + currents after depolarization were slow in k-shy compared to wild type. To identify protein targets of Ca 2+ action, ciliary proteins that interact with calmodulin (CaM) were characterized. With a 125 I-CaM blot assay, several CaM-binding proteins were identified including axonemal, soluble, and membrane-bound polypeptides. Competitive displacement studies with unlabeled Paramecium CaM, bovine CaM, and troponinC suggested that both protein types bind CaM with high affinity and specificity. To examine the presence of CaM-binding sites in intact axonemes, a filtration binding assay was developed

  18. Chloral hydrate alters the organization of the ciliary basal apparatus and cell organelles in sea urchin embryos (United States)

    Chakrabarti, A.; Schatten, H.; Mitchell, K. D.; Crosser, M.; Taylor, M.


    The mitotic inhibitor, chloral hydrate, induces ciliary loss in the early embryo phase of Lytechinus pictus. It causes a breakdown of cilia at the junction of the cilium and the basal body known as the basal plate. This leaves the plasma membrane temporarily unsealed. The basal apparatus accessory structures, consisting of the basal body, basal foot, basal foot cap, striated side arm, and striated rootlet, are either misaligned or disintegrated by treatment with chloral hydrate. Furthermore, microtubules which are associated with the basal apparatus are disassembled. Mitochondria accumulate at the base of cilia - underneath the plasma membrane - and show alterations in their structural organization. The accumulation of mitochondria is observed in 40% of all electron micrograph sections while 60% show the areas mostly devoid of mitochondria. The microvilli surrounding a cilium and striated rootlet remain intact in the presence of chloral hydrate. These results suggest that deciliation in early sea urchin embryos by chloral hydrate is caused by combined effects on the ciliary membrane and on microtubules in the cilia. Furthermore, it is suggested that chloral hydrate can serve as a tool to explore the cytoskeletal mechanisms that are involved in cilia motility in the developing sea urchin embryo.

  19. The eye-catching cicada Hamza ciliaris (Linnaeus, 1758) comb. n. in Indonesia and the Pacific: taxonomie status, synonymy, and distribution (Homoptera, Cicadoidea)

    NARCIS (Netherlands)

    Duffels, J.P.


    The new combination Hamza ciliaris (Linnaeus) is proposed for a cicada species widely distributed in Maluku ( = Moluccas), Timor, Banda, Kei and Banggai Islands, the Philippines, and the Palau group of the Caroline Islands. The synonymy of five species, treated in the literature as junior synonyms

  20. Exhaled breath analysis using electronic nose in cystic fibrosis and primary ciliary dyskinesia patients with chronic pulmonary infections

    DEFF Research Database (Denmark)

    Joensen, Odin; Paff, Tamara; Haarman, Eric G


    The current diagnostic work-up and monitoring of pulmonary infections may be perceived as invasive, is time consuming and expensive. In this explorative study, we investigated whether or not a non-invasive exhaled breath analysis using an electronic nose would discriminate between cystic fibrosis...... (CF) and primary ciliary dyskinesia (PCD) with or without various well characterized chronic pulmonary infections. We recruited 64 patients with CF and 21 with PCD based on known chronic infection status. 21 healthy volunteers served as controls. An electronic nose was employed to analyze exhaled......, this method significantly discriminates CF patients suffering from a chronic pulmonary P. aeruginosa (PA) infection from CF patients without a chronic pulmonary infection. Further studies are needed for verification and to investigate the role of electronic nose technology in the very early diagnostic workup...

  1. Long-term follow-up of patients with retinitis pigmentosa (RP) receiving intraocular ciliary neurotrophic factor implants (United States)

    Birch, David G.; Bennett, Lea D.; Duncan, Jacque L.; Weleber, Richard G.; Pennesi, Mark E.


    Purpose To evaluate the long-term efficacy of ciliary neurotrophic factor delivered via an intraocular encapsulated cell implant for the treatment of retinitis pigmentosa (RP). Design Long-term follow up of a multicenter, sham-controlled study. Methods Thirty-six patients at three CNTF4 sites were randomly assigned to receive a high- or low- dose implant in one eye and sham surgery in the fellow eye. The primary endpoint (change in visual field sensitivity at 12 months) has been reported previously.1 Here we report long-term visual acuity, visual field and optical coherence tomography (OCT) outcomes in 24 patients either retaining or explanting the device at 24 months relative to sham-treated eyes. Results Eyes retaining the implant showed significantly greater visual field loss from baseline than either explanted eyes or sham eyes through 42 months. By 60 months and continuing through 96 months, visual field loss was comparable among sham-treated eyes, eyes retaining the implant and explanted eyes, as was visual acuity and OCT macular volume. Conclusions Over the short term, ciliary neurotrophic factor released continuously from an intra-vitreal implant lead to loss of total visual field sensitivity that was greater than the natural progression in the sham-treated eye. This additional loss of sensitivity related to the active implant was reversible when the implant was removed. Over the long term (60 – 96 months), there was no evidence of efficacy for visual acuity, visual field sensitivity or OCT measures of retinal structure. PMID:27457255

  2. The development of the larval nervous system, musculature and ciliary bands of Pomatoceros lamarckii (Annelida: heterochrony in polychaetes

    Directory of Open Access Journals (Sweden)

    Shimeld Sebastian M


    Full Text Available Abstract Background To understand the evolution of animals it is essential to have taxon sampling across a representative spread of the animal kingdom. With the recent rearrangement of most of the Bilateria into three major clades (Ecdysozoa, Lophotrochozoa and Deuterostomia it has become clear that the Lophotrochozoa are relatively poorly represented in our knowledge of animal development, compared to the Ecdysozoa and Deuterostomia. We aim to contribute towards redressing this balance with data on the development of the muscular, nervous and ciliary systems of the annelid Pomatoceros lamarckii (Serpulidae. We compare our data with other lophotrochozoans. Results P. lamarckii develops locomotory and feeding structures that enable it to become a swimming, planktotrophic larva within 24 hours. Formation of the trochophore includes development of a prototroch, metatroch and neurotroch, development of apical and posterior nervous elements at similar times, and development of musculature around the ciliary bands and digestive tract prior to development of any body wall muscles. The adult nervous and muscular systems are essentially preformed in the late larva. Interestingly, the muscular systems of the larvae and juvenile worms do not include the circular muscles of the body wall, which are considered to be plesiomorphic for annelids, although the possibility that circular muscles develop after these stages cannot be ruled out at this point. Conclusion A comparison between polychaetes shows variability in the timing (heterochrony of development of body wall muscles and elements of the nervous system. These heterochronies are one route for evolution of different life history strategies, such as adaptations to feeding requirements.

  3. Dermoscopy of a non-pigmented eccrine poroma

    Directory of Open Access Journals (Sweden)

    Maria Clara De Diego


    Full Text Available Eccrine poroma is a benign adnexal tumor arising from cells of the outer layer of the acrosyringium and upper dermal eccrine duct. It generally appears as a solitary, slow growing, sessile, pink-to-red and well-circumscribed papule, plaque or nodule. It is usually located on the palms and soles but it may also develop on other locations. Its clinical appearance can resemble other types of tumors such as hypo- or amelanotic melanoma. Dermoscopy has  improved the evaluation of skin tumors. In the case of eccrine poroma, there are some studies that have described its dermoscopic findings. These mainly focus on its vascular structures. We present an 82-year-old patient who developed a 2×3-cm eccrine poroma on his lower back. Dermoscopy demonstrated the presence of a polymorphous vascular pattern displaying mostly linear looped (irregular hairpin-like and “leaf-flower-like” vessels (“cherry-blossom” and “chalice-like”, with some resembling “cactus-like” structures. Only a few linear coiled (glomerular and linear helical (corkscrew vessels were observed. Some of these vascular structures were surrounded by a whitish-to-pink halo. Moreover, some pink structureless areas were present. We highlight the finding of the “leaf-flower-like” vessels, as these are vascular structures that have not been described in other types of skin tumors.

  4. Aquaporins 6-12 in the human eye

    DEFF Research Database (Denmark)

    Tran, Thuy Linh; Bek, Toke; Holm, Lars


    Purpose: Aquaporins (AQPs) are widely expressed and have diverse distribution patterns in the eye. AQPs 0-5 have been localized at the cellular level in human eyes. We investigated the presence of the more recently discovered AQPs 6-12 in the human eye. Methods: RT-PCR was performed on fresh tissue...... from two human eyes divided into the cornea, corneal limbus, ciliary body and iris, lens, choroid, optic nerve, retina and sclera. Each structure was examined to detect the mRNA of AQPs 6-12. Twenty-one human eyes were examined using immunohistochemical and immunofluorescence techniques to determine...... was detected in the corneal epithelium, corneal endothelium, trabecular meshwork endothelium, ciliary epithelia, lens epithelium, the inner and outer limiting membrane of the retina, the retinal pigment epithelium and the capillary endothelium of all parts of the eye. AQP9 immunolabelling was detected...

  5. Hyperglycemia in Streptozotocin-Induced Diabetes Leads to Persistent Inflammation and Tissue Damage Following Uveitis Due to Reduced Levels of Ciliary Body Heme Oxygenase-1

    Directory of Open Access Journals (Sweden)


    Full Text Available This study investigated the heme oxygenase-1 (HO-1 and the endotoxin-induced uveitis (EIU in diabetic streptozotocin (STZ-hyperglycemic rats. STZ-hyperglycemic rats had impaired levels of the enzyme HO-1 within the ciliary bodies if compared with the nondiabetic rats. STZ-hyperglycemic rats also predisposed the eye to produce high levels of both the cytokines IL-1 β and CXCL8. Subsequent EIU further and significantly P<.01 increased the cytokines production, an effect partly prevented by hemin treatment. Most importantly, hemin, an inducer of heme oxygenase expression and activity, recovered the huge number of infiltrated polymorphonuclear leukocytes PMN within the ciliary bodies associated with STZ-hyperglycemic state and EIU damage. Impairment of the stress-sensitive enzyme HO-1 in STZ-hyperglycemic rats increases and prolongs the inflammatory response to EIU.

  6. Immunohistochemical and ultrastructural properties of the larval ciliary band-associated strand in the sea urchin Hemicentrotus pulcherrimus. (United States)

    Katow, Hideki; Katow, Tomoko; Yoshida, Hiromi; Kiyomoto, Masato; Uemura, Isao


    The swimming activity of sea urchin larvae is dependent on the ciliary band (CB) on the larval surface and is regulated by several neurotransmitters, including serotonin (5HT), dopamine, and γ-aminobutyric acid (GABA). However, the CB signal transmission mechanism remains unknown. The present study investigated the structural relationship between the CB and external signal receptors by immunohistochemical and transmission electron microscopic analyses of sea urchin, Hemicentrotus pulcherrimus, larvae. Glutamate decarboxylase (GAD; GABA synthetase) was detected in a strand of multiple cells along the circumoral CB in 6-arm plutei. The GAD-expressing strand was closely associated with the CB on the oral ectoderm side. The ciliary band-associated strand (CBAS) also expressed the 5HT receptor (5HThpr) and encephalopsin (ECPN) throughout the cytoplasm and comprised 1- to 2-μm diameter axon-like long stretched regions and sporadic 6- to 7-μm diameter bulbous nucleated regions (perikarya) that protruded into the oral ectoderm side. Besides the laterally polarized morphology of the CBAS cells, Epith-2, which is the epithelial lateral cell surface-specific protein of the sea urchin embryo and larva, was expressed exclusively by perikarya but not by the axon-like regions. The CBAS exposed its narrow apical surface on the larval epithelium between the CB and squamous cells and formed adherens junctions (AJs) on the apical side between them. Despite the presence of the CBAS axon-like regions, tubulins, such as α-, β-, and acetylated α-tubulins, were not detected. However, the neuroendocrine cell marker protein synaptophysin was detected in the axon-like regions and in bouton-like protrusions that contained numerous small ultrastructural vesicles. The unique morphology of the CBAS in the sea urchin larva epithelium had not been reported. The CBAS expresses a remarkable number of receptors to environmental stimuli and proteins that are probably involved in signal

  7. The ciliary marginal zone of the zebrafish retina: clonal and time-lapse analysis of a continuously growing tissue. (United States)

    Wan, Yinan; Almeida, Alexandra D; Rulands, Steffen; Chalour, Naima; Muresan, Leila; Wu, Yunmin; Simons, Benjamin D; He, Jie; Harris, William A


    Clonal analysis is helping us understand the dynamics of cell replacement in homeostatic adult tissues (Simons and Clevers, 2011). Such an analysis, however, has not yet been achieved for continuously growing adult tissues, but is essential if we wish to understand the architecture of adult organs. The retinas of lower vertebrates grow throughout life from retinal stem cells (RSCs) and retinal progenitor cells (RPCs) at the rim of the retina, called the ciliary marginal zone (CMZ). Here, we show that RSCs reside in a niche at the extreme periphery of the CMZ and divide asymmetrically along a radial (peripheral to central) axis, leaving one daughter in the peripheral RSC niche and the other more central where it becomes an RPC. We also show that RPCs of the CMZ have clonal sizes and compositions that are statistically similar to progenitor cells of the embryonic retina and fit the same stochastic model of proliferation. These results link embryonic and postembryonic cell behaviour, and help to explain the constancy of tissue architecture that has been generated over a lifetime. © 2016. Published by The Company of Biologists Ltd.

  8. Whole-Exome Sequencing Identified a Novel Compound Heterozygous Mutation of LRRC6 in a Chinese Primary Ciliary Dyskinesia Patient

    Directory of Open Access Journals (Sweden)

    Lv Liu


    Full Text Available Primary ciliary dyskinesia (PCD is a clinical rare peculiar disorder, mainly featured by respiratory infection, tympanitis, nasosinusitis, and male infertility. Previous study demonstrated it is an autosomal recessive disease and by 2017 almost 40 pathologic genes have been identified. Among them are the leucine-rich repeat- (LRR- containing 6 (LRRC6 codes for a 463-amino-acid cytoplasmic protein, expressed distinctively in motile cilia cells, including the testis cells and the respiratory epithelial cells. In this study, we applied whole-exome sequencing combined with PCD-known genes filtering to explore the genetic lesion of a PCD patient. A novel compound heterozygous mutation in LRRC6 (c.183T>G/p.N61K; c.179-1G>A was identified and coseparated in this family. The missense mutation (c.183T>G/p.N61K may lead to a substitution of asparagine by lysine at position 61 in exon 3 of LRRC6. The splice site mutation (c.179-1G>A may cause a premature stop codon in exon 4 and decrease the mRNA levels of LRRC6. Both mutations were not present in our 200 local controls, dbSNP, and 1000 genomes. Three bioinformatics programs also predicted that both mutations are deleterious. Our study not only further supported the importance of LRRC6 in PCD, but also expanded the spectrum of LRRC6 mutations and will contribute to the genetic diagnosis and counseling of PCD patients.

  9. Segmental allotetraploidy and allelic interactions in buffelgrass (Pennisetum ciliare (L.) Link syn. Cenchrus ciliaris L.) as revealed by genome mapping. (United States)

    Jessup, R W; Burson, B L; Burow, O; Wang, Y W; Chang, C; Li, Z; Paterson, A H; Hussey, M A


    Linkage analyses increasingly complement cytological and traditional plant breeding techniques by providing valuable information regarding genome organization and transmission genetics of complex polyploid species. This study reports a genome map of buffelgrass (Pennisetum ciliare (L.) Link syn. Cenchrus ciliaris L.). Maternal and paternal maps were constructed with restriction fragment length polymorphisms (RFLPs) segregating in 87 F1 progeny from an intraspecific cross between two heterozygous genotypes. A survey of 862 heterologous cDNAs and gDNAs from across the Poaceae, as well as 443 buffelgrass cDNAs, yielded 100 and 360 polymorphic probes, respectively. The maternal map included 322 RFLPs, 47 linkage groups, and 3464 cM, whereas the paternal map contained 245 RFLPs, 42 linkage groups, and 2757 cM. Approximately 70 to 80% of the buffelgrass genome was covered, and the average marker spacing was 10.8 and 11.3 cM on the respective maps. Preferential pairing was indicated between many linkage groups, which supports cytological reports that buffelgrass is a segmental allotetraploid. More preferential pairing (disomy) was found in the maternal than paternal parent across linkage groups (55 vs. 38%) and loci (48 vs. 15%). Comparison of interval lengths in 15 allelic bridges indicated significantly less meiotic recombination in paternal gametes. Allelic interactions were detected in four regions of the maternal map and were absent in the paternal map.

  10. A Low-Cost Method of Ciliary Beat Frequency Measurement Using iPhone and MATLAB: Rabbit Study. (United States)

    Chen, Jason J; Lemieux, Bryan T; Wong, Brian J F


    (1) To determine ciliary beat frequency (CBF) using a consumer-grade cellphone camera and MATLAB and (2) to evaluate the effectiveness and accuracy of the proposed method. Prospective animal study. Academic otolaryngology department research laboratory. Five ex vivo tracheal samples were extracted from 3 freshly euthanized (MATLAB programming, the video of the 23°C sample was downsampled to 120, 60, and 30 fps, and Fourier analysis was performed on videos of all frame rates and conditions to determine CBF. CBF of the 23°C sample was also calculated manually frame by frame for verification. Recorded at 240 fps, the CBF at 23°C was 5.03 ± 0.4 Hz, and the CBF at 37°C was 9.08 ± 0.49 Hz (P .05). There is no significant difference between CBF measured via visual inspection and that analyzed by the developed program. Furthermore, all tested acquisition rates are shown to be effective, providing a fast and inexpensive alternative to current CBF measurement protocols. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  11. Disruption of the mouse Jhy gene causes abnormal ciliary microtubule patterning and juvenile hydrocephalus (United States)

    Appelbe, Oliver K.; Bollman, Bryan; Attarwala, Ali; Triebes, Lindy A.; Muniz-Talavera, Hilmarie; Curry, Daniel J.; Schmidt, Jennifer V.


    SUMMARY Congenital hydrocephalus, the accumulation of excess cerebrospinal fluid (CSF) in the ventricles of the brain, affects one of every 1,000 children born today, making it one of the most common human developmental disorders. Genetic causes of hydrocephalus are poorly understood in humans, but animal models suggest a broad genetic program underlying the regulation of CSF balance. In this study, the random integration of a transgene into the mouse genome led to the development of an early onset and rapidly progressive hydrocephalus. Juvenile hydrocephalus transgenic mice (JhylacZ) inherit communicating hydrocephalus in an autosomal recessive fashion with dilation of the lateral ventricles observed as early as postnatal day 1.5. Ventricular dilation increases in severity over time, becoming fatal at 4-8 weeks of age. The ependymal cilia lining the lateral ventricles are morphologically abnormal and reduced in number in JhylacZ/lacZ brains, and ultrastructural analysis revealed disorganization of the expected 9+2 microtubule pattern. Rather, the majority of JhylacZ/lacZ cilia develop axonemes with 9+0 or 8+2 microtubule structures. Disruption of an unstudied gene, 4931429I11Rik (now named Jhy) appears to underlie the hydrocephalus of JhylacZ/lacZ mice, and the Jhy transcript and protein are decreased in JhylacZ/lacZ mice. Partial phenotypic rescue was achieved in JhylacZ/lacZ mice by the introduction of a bacterial artificial chromosome (BAC) carrying 60-70% of the JHY protein coding sequence. Jhy is evolutionarily conserved from humans to basal vertebrates, but the predicted JHY protein lacks identifiable functional domains. Ongoing studies are directed at uncovering the physiological function of JHY and its role in CSF homeostasis. PMID:23906841

  12. CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function

    Directory of Open Access Journals (Sweden)

    Peter Canning


    Full Text Available Various kinases, including a cyclin-dependent kinase (CDK family member, regulate the growth and functions of primary cilia, which perform essential roles in signaling and development. Neurological disorders linked to CDK-Like (CDKL proteins suggest that these underexplored kinases may have similar functions. Here, we present the crystal structures of human CDKL1, CDKL2, CDKL3, and CDKL5, revealing their evolutionary divergence from CDK and mitogen-activated protein kinases (MAPKs, including an unusual αJ helix important for CDKL2 and CDKL3 activity. C. elegans CDKL-1, most closely related to CDKL1–4 and localized to neuronal cilia transition zones, modulates cilium length; this depends on its kinase activity and αJ helix-containing C terminus. Human CDKL5, linked to Rett syndrome, also localizes to cilia, and it impairs ciliogenesis when overexpressed. CDKL5 patient mutations modeled in CDKL-1 cause localization and/or cilium length defects. Together, our studies establish a disease model system suggesting cilium length defects as a pathomechanism for neurological disorders, including epilepsy.

  13. Non‐diluted seawater enhances nasal ciliary beat frequency and wound repair speed compared to diluted seawater and normal saline (United States)

    Bonnomet, Arnaud; Luczka, Emilie; Coraux, Christelle


    Background The regulation of mucociliary clearance is a key part of the defense mechanisms developed by the airway epithelium. If a high aggregate quality of evidence shows the clinical effectiveness of nasal irrigation, there is a lack of studies showing the intrinsic role of the different irrigation solutions allowing such results. This study investigated the impact of solutions with different pH and ionic compositions, eg, normal saline, non‐diluted seawater and diluted seawater, on nasal mucosa functional parameters. Methods For this randomized, controlled, blinded, in vitro study, we used airway epithelial cells obtained from 13 nasal polyps explants to measure ciliary beat frequency (CBF) and epithelial wound repair speed (WRS) in response to 3 isotonic nasal irrigation solutions: (1) normal saline 0.9%; (2) non‐diluted seawater (Physiomer®); and (3) 30% diluted seawater (Stérimar). The results were compared to control (cell culture medium). Results Non‐diluted seawater enhanced the CBF and the WRS when compared to diluted seawater and to normal saline. When compared to the control, it significantly enhanced CBF and slightly, though nonsignificantly, improved the WRS. Interestingly, normal saline markedly reduced the number of epithelial cells and ciliated cells when compared to the control condition. Conclusion Our results suggest that the physicochemical features of the nasal wash solution is important because it determines the optimal conditions to enhance CBF and epithelial WRS thus preserving the respiratory mucosa in pathological conditions. Non‐diluted seawater obtains the best results on CBF and WRS vs normal saline showing a deleterious effect on epithelial cell function. PMID:27101776

  14. Influence of Maternal Undernutrition and Overfeeding on Cardiac Ciliary Neurotrophic Factor Receptor and Ventricular Size in Fetal Sheep (United States)

    Dong, Feng; Ford, Stephen P.; Nijland, Mark J.; Nathanielsz, Peter W.; Ren, Jun


    Intrauterine nutrition status is reported to correlate with risk of cardiovascular diseases in adulthood. Either under- or over-nutrition during early to mid gestation contributes to altered fetal growth and ventricular geometry. This study was designed to examine myocardial expression of ciliary neurotrophic factor receptor α (CTNFRα) and its down-stream mediator signal transducer and activator of transcription 3 (STAT3) on maternal under- or over-nutrition-induced changes in fetal heart weight. Multiparous ewes were fed with 50% (nutrient-restricted, NR), 100% (control) or 150% (overfed, OF) of NRC requirements from 28 to 78 days of gestation (dG; Term 148 dG). Ewes were euthanized on day 78, and the gravid uteri and fetuses recovered. Ventricular protein expression of CTNFRα, STAT3, phosphorylated STAT3, insulin-like growth factor I receptor (IGF-1R) and IGF binding protein 3 (IGFBP3) were quantitated using western blot. Plasma cortisol levels were higher in both NR and OF fetuses whereas plasma IGF-1 levels were lower and higher, in NR and OF fetuses. Fetal weights were reduced by 29.9% in NR ewes and were increased by 22.2% in fetuses from OF ewes compared to control group. Nutrient restriction did not affect fetal heart or ventricular weights whereas overfeeding increased heart and ventricular weights. Protein expression of CTNFRα in fetal ventricular tissue was reduced in OF group whereas STAT3 and pSTAT3 levels were reduced in both NR and OF groups. Expression of IGF-1R and IGFBP3 was unaffected in either NR or OF group. These data suggested that compared with maternal undernutrition, intrauterine overfeeding during early to mid gestation is associated with increases fetal blood concentrations of cortisol and IGF-1 in association with ventricular hypertrophy where reduced expression of CNTFRα and STAT3 may play a role. PMID:17869083

  15. Non-diluted seawater enhances nasal ciliary beat frequency and wound repair speed compared to diluted seawater and normal saline. (United States)

    Bonnomet, Arnaud; Luczka, Emilie; Coraux, Christelle; de Gabory, Ludovic


    The regulation of mucociliary clearance is a key part of the defense mechanisms developed by the airway epithelium. If a high aggregate quality of evidence shows the clinical effectiveness of nasal irrigation, there is a lack of studies showing the intrinsic role of the different irrigation solutions allowing such results. This study investigated the impact of solutions with different pH and ionic compositions, eg, normal saline, non-diluted seawater and diluted seawater, on nasal mucosa functional parameters. For this randomized, controlled, blinded, in vitro study, we used airway epithelial cells obtained from 13 nasal polyps explants to measure ciliary beat frequency (CBF) and epithelial wound repair speed (WRS) in response to 3 isotonic nasal irrigation solutions: (1) normal saline 0.9%; (2) non-diluted seawater (Physiomer®); and (3) 30% diluted seawater (Stérimar). The results were compared to control (cell culture medium). Non-diluted seawater enhanced the CBF and the WRS when compared to diluted seawater and to normal saline. When compared to the control, it significantly enhanced CBF and slightly, though nonsignificantly, improved the WRS. Interestingly, normal saline markedly reduced the number of epithelial cells and ciliated cells when compared to the control condition. Our results suggest that the physicochemical features of the nasal wash solution is important because it determines the optimal conditions to enhance CBF and epithelial WRS thus preserving the respiratory mucosa in pathological conditions. Non-diluted seawater obtains the best results on CBF and WRS vs normal saline showing a deleterious effect on epithelial cell function. © 2016 The Authors International Forum of Allergy & Rhinology, published by ARSAAOA, LLC.

  16. Vicks VapoRub induces mucin secretion, decreases ciliary beat frequency, and increases tracheal mucus transport in the ferret trachea. (United States)

    Abanses, Juan Carlos; Arima, Shinobu; Rubin, Bruce K


    Vicks VapoRub (VVR) [Proctor and Gamble; Cincinnati, OH] is often used to relieve symptoms of chest congestion. We cared for a toddler in whom severe respiratory distress developed after VVR was applied directly under her nose. We hypothesized that VVR induced inflammation and adversely affected mucociliary function, and tested this hypothesis in an animal model of airway inflammation. [1] Trachea specimens excised from 15 healthy ferrets were incubated in culture plates lined with 200 mg of VVR, and the mucin secretion was compared to those from controls without VVR. Tracheal mucociliary transport velocity (MCTV) was measured by timing the movement of 4 microL of mucus across the trachea. Ciliary beat frequency (CBF) was measured using video microscopy. [2] Anesthetized and intubated ferrets inhaled a placebo or VVR that was placed at the proximal end of the endotracheal tube. We evaluated both healthy ferrets and animals in which we first induced tracheal inflammation with bacterial endotoxin (a lipopolysaccharide [LPS]). Mucin secretion was measured using an enzyme-linked lectin assay, and lung water was measured by wet/dry weight ratios. [1] Mucin secretion was increased by 63% over the controls in the VVR in vitro group (p < 0.01). CBF was decreased by 35% (p < 0.05) in the VVR group. [2] Neither LPS nor VVR increased lung water, but LPS decreased MCTV in both normal airways (31%) and VVR-exposed airways (30%; p = 0.03), and VVR increased MCTV by 34% in LPS-inflamed airways (p = 0.002). VVR stimulates mucin secretion and MCTV in the LPS-inflamed ferret airway. This set of findings is similar to the acute inflammatory stimulation observed with exposure to irritants, and may lead to mucus obstruction of small airways and increased nasal resistance.

  17. Use of a novel cell adhesion method and digital measurement to show stimulus-dependent variation in somatic and oral ciliary beat frequency in Paramecium. (United States)

    Bell, Wade E; Hallworth, Richard; Wyatt, Todd A; Sisson, Joseph H


    When Paramecium encounters positive stimuli, the membrane hyperpolarizes and ciliary beat frequency increases. We adapted an established immobilization protocol using a biological adhesive and a novel digital analysis system to quantify beat frequency in immobilized Paramecium. Cells showed low mortality and demonstrated beat frequencies consistent with previous studies. Chemoattractant molecules, reduction in external potassium, and posterior stimulation all increased somatic beat frequency. In all cases, the oral groove cilia maintained a higher beat frequency than mid-body cilia, but only oral cilia from cells stimulated with chemoattactants showed an increase from basal levels. © 2014 The Author(s) Journal of Eukaryotic Microbiology © 2014 International Society of Protistologists.

  18. Validation of a health-related quality of life instrument for primary ciliary dyskinesia (QOL-PCD). (United States)

    Behan, Laura; Leigh, Margaret W; Dell, Sharon D; Dunn Galvin, Audrey; Quittner, Alexandra L; Lucas, Jane S


    Quality of life (QOL)-primary ciliary dyskinesia (PCD) is the first disease-specific, health-related QOL instrument for PCD. Psychometric validation of QOL-PCD assesses the performance of this measure in adults, including its reliability, validity and responsiveness to change. Seventy-two adults (mean (range) age: 33 years (18-79 years); mean (range) FEV 1 % predicted: 68 (26-115)) with PCD completed the 49-item QOL-PCD and generic QOL measures: Short-Form 36 Health Survey, Sino-Nasal Outcome Test 20 (SNOT-20) and St George Respiratory Questionnaire (SGRQ)-C. Thirty-five participants repeated QOL-PCD 10-14 days later to measure stability or reproducibility of the measure. Multitrait analysis was used to evaluate how the items loaded on 10 hypothesised scales: physical, emotional, role and social functioning, treatment burden, vitality, health perceptions, upper respiratory symptoms, lower respiratory symptoms and ears and hearing symptoms. This analysis of item-to-total correlations led to 9 items being dropped; the validated measure now comprises 40 items. Each scale had excellent internal consistency (Cronbach's α: 0.74 to 0.94). Two-week test-retest demonstrated stability for all scales (intraclass coefficients 0.73 to 0.96). Significant correlations were obtained between QOL-PCD scores and age and FEV 1 . Strong relationships were also found between QOL-PCD scales and similar constructs on generic questionnaires, for example, lower respiratory symptoms and SGRQ-C (r=0.72, pmeasures of different constructs. QOL-PCD has demonstrated good internal consistency, test-retest reliability, convergent and divergent validity. QOL-PCD offers a promising tool for evaluating new therapies and for measuring symptoms, functioning and QOL during routine care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  19. Ciliary derived neurotrophic factor protects oligodendrocytes against radiation induced damage in vitro by a mechanism independent of a proliferative effect

    International Nuclear Information System (INIS)

    Evans, Andrew J.; Mabie, Peter C.; Kessler, Jack A.; Vikram, Bhadrasain


    Purpose/Objective: Radiation-induced damage to the central nervous system in the from of myelopathy is a dose-limiting complication in the treatment of tumors situated in or close to the spinal cord. The target cell for this damage is not definitively identified, but demyelination due to oligodendrocyte damage is strongly implicated. Multiple neurotrophic factors have recently been identified which demonstrate a survival effect on oligodendrocytes. We investigated the effect of Ciliary Derived Neurotrophic Factor (CNTF), Neurotrophin-3 (NT-3) and Nerve Growth Factor (NGF) on the radiosensitivity of oligodendrocytes in vitro to determine if this may ameliorate radiation damage, as a model for reducing myelopathy in vivo. Materials and Methods: Mature oligodendrocytes were cultured from the cortex of newborn Sprague-Dawley white rats and maintained on poly-d-lysine plates. The experimental arm was exposed to CNTF (0.01-100ng/ml), NGF (100ng/ml) or NT-3 (20ng/ml) for 24 hours prior to radiation, and control and experimental arms radiated using a cobalt 60 irradiator at a dose rate of .87 Gy/min with doses from 2 Gy to 10 Gy. Oligodendrocytes were identified using an O4 antibody, assessed for viability at 5 days using an MTT assay and counted using a phase contrast microscope. Combination studies of CNTF and NT-3 were also performed. BrdU studies were performed to determine if the various neurotrophins induced proliferation, with BrdU added for the 24 hour period prior to radiation only, for the 5 day period following radiation only, or for both periods combined. Results: The proportion of mature oligodendrocytes surviving 5 days after irradiation was not significantly increased by NGF, and was only modestly increased by NT-3. However, CNTF significantly increased the surviving proportion at all doses The addition of NT-3 to CNTF did not further increase the proportion of oligodendrocytes surviving. CNTF dose escalation studies confirmed 20ng/ml as an optimal dose. Brd

  20. [Lens exchange for subluxation of posterior chamber lenses implanted in the capsular bag or in the ciliary sulcus]. (United States)

    Stürmer, J


    There are an increasing number of patients with decreased vision due to dislocated posterior chamber lenses, with pseudoexfoliation being the main risk factor. Various techniques for refixation of the subluxated posterior chamber IOL have been described. Experience with our technique of IOL-explantation, anterior vitrectomy and implantation of an Artisan anterior chamber lens are presented. In a retrospective study design all lens exchanges with implantation of an Artisan anterior chamber lens performed between 2003 and 2012 are analyzed. The study included 65 eyes of 61 patients (age 79.6 ± 9.2 years: 43-98). The majority of eyes (46/65; 70.8%) had Sundown Syndrome (late in-the-bag intraocular lens dislocation), in 19 eyes the posterior chamber lens was implanted primary or secondary into the ciliary sulcus. In the 46 eyes with Sundown Syndrome cataract surgery with implantation of a posterior chamber lens in the capsular bag was performed 7.4 ± 3.7 (1-22) years before subluxation within the bag. Pseudoexfoliation was the main risk factor in 42/46 (91.2%) of these eyes. A capsular tension ring (CTR) was implanted during cataract surgery in 34/46 (73.9%) eyes. The 34 IOLs with a CTR luxated significantly earlier (p IOLs without a CTR (6.6 ± 3.6 years; median 5.8 vs. 9.4 ± 3.1 years; median 9.2). The average visual gain was 0.2 logMAR in the group of luxated capsular bag lenses and 0.12 logMAR in the group of luxated sulcus lenses. Postoperative IOP decompensation was seen in 17/65 (26.2%) eyes (requiring IOP-lowering surgery in 8 eyes), 7 eyes developed corneal decompensation, 5 eyes had central retinal vein occlusion and one eye developed postoperative endophthalmitis. Lens exchange with implantation of an Artisan anterior chamber lens has become a routine procedure to improve vision in patients with subluxated IOLs. Postoperative IOP decompensation and vascular problems are the major complications. Georg Thieme Verlag KG Stuttgart · New York.

  1. Cyclooxygenase-2 expression in the normal human eye and its expression pattern in selected eye tumours

    DEFF Research Database (Denmark)

    Wang, Jinmei; Wu, Yazhen; Heegaard, Steffen


    Purpose: Cyclooxygenase-2 (COX-2) is an enzyme involved in neoplastic processes. The purpose of the present study is to investigate COX-2 expression in the normal human eye and the expression pattern in selected eye tumours involving COX-2 expressing cells. Methods: Immunohistochemical staining...... using antibodies against COX-2 was performed on paraffin sections of normal human eyes and selected eye tumours arising from cells expressing COX-2. Results: Cyclooxygenase-2 expression was found in various structures of the normal eye. Abundant expression was seen in the cornea, iris, ciliary body...... and retina. The COX-2 expression was less in tumours deriving from the ciliary epithelium and also in retinoblastoma. Conclusion: Cyclooxygenase-2 is constitutively expressed in normal human eyes. The expression of COX-2 is much lower in selected eye tumours involving COX-2 expressing cells....

  2. Digitaria ciliaris (Retz.) Koeler

    Czech Academy of Sciences Publication Activity Database

    Danihelka, Jiří


    Roč. 46, č. 1 (2011), s. 85-87 ISSN 1211-5258 R&D Projects: GA MŠk LC06073 Institutional research plan: CEZ:AV0Z60050516 Keywords : alien species * Czech Republic * neophyte Subject RIV: EF - Botanics

  3. Primary Ciliary Dyskinesia (United States)

    ... made to help with CPT, such as: An electric chest clapper, known as a mechanical percussor. An ... your child spends time, including the home and car. Encourage your child to never start smoking. For ...

  4. Hand-held tidal breathing nasal nitric oxide measurement--a promising targeted case-finding tool for the diagnosis of primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Marthin, June Kehlet; Nielsen, Kim Gjerum


    BACKGROUND: Nasal nitric oxide (nNO) measurement is an established first line test in the work-up for primary ciliary dyskinesia (PCD). Tidal breathing nNO (TB-nNO) measurements require minimal cooperation and are potentially useful even in young children. Hand-held NO devices are becoming...... increasingly widespread for asthma management. Therefore, we chose to assess whether hand-held TB-nNO measurements reliably discriminate between PCD, and Healthy Subjects (HS) and included Cystic Fibrosis (CF) patients as a disease control group known to have intermediate nNO levels. METHODS: In this cross...... sectional, single centre, single occasion, proof-of-concept study in children and adults with PCD and CF, and in HS we compared feasibility, success rates, discriminatory capacity, repeatability and agreement between a hand-held electrochemical device equipped with a nNO software application sampling...

  5. Expression and prognostic value of putative cancer stem cell markers CD117 and CD15 in choroidal and ciliary body melanoma. (United States)

    Lukenda, Adrian; Dotlic, Snjezana; Vukojevic, Nenad; Saric, Borna; Vranic, Semir; Zarkovic, Kamelija


    The aim of the present study was to immunohistochemically investigate the expression and prognostic significance of putative cancer stem cell markers CD117 (c-kit), CD34, CD20 and CD15 in a cohort of patients with primary choroidal and ciliary body melanoma. The immunohistochemical expression of these markers was evaluated using 3,3'-diaminobenzidine tetrahydrochloride (DAB) and 3-amino-9-ethylcarbazole (AEC) chromogens on paraffin-embedded tissue samples from 40 patients who underwent enucleation in the period from 1985 through 2000. Thirty-one patients had adequate tissue specimens for the analysis. CD117 overexpression was observed in 12 of the 31 samples (39%) when AEC chromogen was used and in 14 of 26 (54%) samples when DAB was used. CD15 positivity was seen in three out of 30 (10%) samples with AEC and in six out of 26 (23%) samples with DAB. CD20 and CD34 exhibited no positivity in the tested samples. During the average follow-up time of 8.7 years (range 0.5-22 years), 17 patients (55%) died due to metastatic disease. The Kaplan-Meier plots showed a significantly shorter overall and disease-free survival in CD117-positive patients when the AEC chromogen was used. CD15 expression was not associated with patients' survival. In multivariate analysis, patients expressing the CD117 AEC had 4.13 times higher risk of lethal outcome in comparison with CD117 AEC negative patients. Our retrospective cohort study has for the first time demonstrated a small proportion of CD15-positive uveal melanomas. CD117 AEC overexpression was associated with a worse outcome in patients with choroidal and ciliary body melanoma. Further studies should confirm the validity of these observations and their potential for targeted treatment modalities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  6. Non-invasive measurements of the dynamic changes in the ciliary muscle, crystalline lens morphology, and anterior chamber during accommodation with a high-resolution OCT. (United States)

    Esteve-Taboada, José J; Domínguez-Vicent, Alberto; Monsálvez-Romín, Daniel; Del Águila-Carrasco, Antonio J; Montés-Micó, Robert


    The purpose of the study was to assess non-invasively the changes in the anterior chamber eye, crystalline lens morphology, and ciliary muscle during accommodation by means of an anterior chamber optical coherence tomographer (OCT), and correlate them with vergence. Twenty-five eyes of twenty-five healthy subjects, whose mean age was 29.9±7.1 years, were included and measured with an anterior chamber OCT. The central corneal thickness (CCT), anterior chamber depth (ACD), anterior crystalline lens radius of curvature (ALRC), crystalline lens thickness (CLT), and ciliary muscle area (CMA) were measured for each participant at 0, -1, -2, and -3 D of target vergence. A linear model was used to assess the correlation of each eye parameter with the vergence demand. The mean CCT showed no change for all the accommodative stimuli. The mean ACD and ALRC decreased with the vergence, about 4.5 and 30 % at -3 D, respectively. On the contrary, the CLT and CMA showed an opposite tendency, where the mean CLT was increased by 4.0 % and the mean CMA was done by 26% at -3 D. Statistical significant differences (p < 0.001) were obtained among all vergences for each eye metric, except for the CCT (p = 0.76). The ACD and ALRC decreased about 2 and 10 % per dioptre of accommodation, respectively; whereas the CLT and CMA increased about 2 and 9 %, respectively. These results add knowledge regarding the understanding of accommodation and give new perspectives for biomechanics and biometry.

  7. Um caso raro de discinesia ciliar primária associada a heterotaxia A rare case of primary ciliary dyskinesia with heterotaxy

    Directory of Open Access Journals (Sweden)

    Cátia Quintela


    Full Text Available A discinesia ciliar primária é uma doença autossómica recessiva caracterizada pela história de infecções de repetição do aparelho respiratório superior e inferior, rinossinusite e bronquite associada a situs inversus completo ou parcial. Os autores apresentam um doente de 78 anos, eurocaucasiano, com rinossinusites, bronquite crónica e dispneia, otite média com défices auditivos, infertilidade, seguido em consulta de gastrenterologia por dispepsia e obstipação há vários anos. Realizou vários exames que mostraram: agenesia frontal direita, espessamento brônquico, bronquiectasias, cego e cólon ascendente localizados na fossa ilíaca esquerda. Excluiu-se imunodeficiência, alergias, fibrose quística e outros. No decurso da investigação concluímos que se tratava de um caso de discinesia ciliar primária. Pela raridade deste caso, decidimos apresentá-lo.Primary ciliary dyskinesia is an autosomal recessive disease with a clinical history of upper and lowers respiratory infections, rhinosinusitis and bronquitis associated with complete or partial situs inversus. The authors present a 78-year-old male caucasian patient with rhinosinusitis, lower respiratory tract infection and dyspnea, chronic otitis with hearing deficit and infertility followed in Gastroenterology for dyspepsia and constipation. The radiological studies revealed agenesis of right frontal sinus; bronchial wall thickening; bronchiectasis; cecum and ascending colon located on the left and small bowel occupies right side of abdomen. He had no immunodeficiency, allergies, cystic fibrosis and others. We concluded primary ciliary dyskinesia with heterotaxy. For the rarity of this case we decided to present it.


    Directory of Open Access Journals (Sweden)

    Efstathios T. Detorakis


    Full Text Available Introduction: A previous study has employed shear-wave ultrasound elastographic imaging to assess corneal rigidity in an ex-vivo porcine eye model. This study employs the same modality in vivo in a rabbit eye model in order to assess lens, ciliary body and total ocular rigidity changes following the instillation of atropine and pilocarpine. Methods: Ten non-pigmented female rabbits were examined. Measurements of the lens, ciliary body and total ocular rigidity as well as lens thickness and anterior chamber depth were taken with the Aixplorer system (SuperSonic Imagine, Aix-en-Provence, France with the SuperLinear™ SL 15-4 transducer in both eyes at baseline as well as after pilocarpine and atropine instillation. The IOP was also measured with the TonoPen tonometer. Results: Changes in rigidity in the examined areas following atropine instillation were statistically not significant. Ciliary body rigidity was significantly increased whereas lens and total ocular rigidity were significantly reduced following pilocarpine instillation. The decrease in lens rigidity following pilocarpine was significantly associated with the respective increase in ciliary body rigidity. Conclusions: Shear-wave ultrasound elastography can detect in vivo rigidity changes in the anterior segment of the rabbit eye model and may potentially be applied in human eyes, providing useful clinical information on conditions in which rigidity changes play an important role, such as glaucoma, pseudoexfoliation syndrome or presbyopia.

  9. Evaluation of iridociliary and lenticular elasticity using shear-wave elastography in rabbit eyes. (United States)

    Detorakis, Efstathios T; Drakonaki, Eleni E; Ginis, Harilaos; Karyotakis, Nikolaos; Pallikaris, Ioannis G


    A previous study has employed shear-wave ultrasound elastographic imaging to assess corneal rigidity in an ex-vivo porcine eye model. This study employs the same modality in vivo in a rabbit eye model in order to assess lens, ciliary body and total ocular rigidity changes following the instillation of atropine and pilocarpine. Ten non-pigmented female rabbits were examined. Measurements of the lens, ciliary body and total ocular rigidity as well as lens thickness and anterior chamber depth were taken with the Aixplorer system (SuperSonic Imagine, Aix-en-Provence, France) with the SuperLinear™ SL 15-4 transducer in both eyes at baseline as well as after pilocarpine and atropine instillation. The IOP was also measured with the TonoPen tonometer. Changes in rigidity in the examined areas following atropine instillation were statistically not significant. Ciliary body rigidity was significantly increased whereas lens and total ocular rigidity were significantly reduced following pilocarpine instillation. The decrease in lens rigidity following pilocarpine was significantly associated with the respective increase in ciliary body rigidity. Shear-wave ultrasound elastography can detect in vivo rigidity changes in the anterior segment of the rabbit eye model and may potentially be applied in human eyes, providing useful clinical information on conditions in which rigidity changes play an important role, such as glaucoma, pseudoexfoliation syndrome or presbyopia.

  10. Neuronal NOS localises to human airway cilia. (United States)

    Jackson, Claire L; Lucas, Jane S; Walker, Woolf T; Owen, Holly; Premadeva, Irnthu; Lackie, Peter M


    Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker β-tubulin in the proximal part of the ciliary axoneme. We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Development of an Anatomically Accurate Finite Element Human Ocular Globe Model for Blast-Related Fluid-Structure Interaction Studies (United States)


    nucleus green ) is attached to the shell of the eye via the zonule fibers (orange) and the ciliary body (pink). The zonule fibers are approximated in shown in the literature.13,24 (a and b) A study conducted by Norman et al.24 with images from normal human subjects sectioned into 15 equal...Fig. 13 Scleral thickness variation procedure in the model: a) scleral thickness variation contours with thickness values noted from Norman et al

  12. Long-term Results of the UCSF-LBNL Randomized Trial: Charged Particle With Helium Ion Versus Iodine-125 Plaque Therapy for Choroidal and Ciliary Body Melanoma

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    Mishra, Kavita K., E-mail: [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Quivey, Jeanne M.; Daftari, Inder K. [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Lawrence Berkeley National Laboratory, Berkeley, California (United States); Weinberg, Vivian [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Cole, Tia B. [The Tumori Foundation, San Francisco, California (United States); Patel, Kishan [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Castro, Joseph R.; Phillips, Theodore L. [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Lawrence Berkeley National Laboratory, Berkeley, California (United States); Char, Devron H. [The Tumori Foundation, San Francisco, California (United States); Department of Ophthalmology, University of California-San Francisco, San Francisco, California (United States); Department of Ophthalmology, Stanford University, Palo Alto, California (United States)


    Purpose: Relevant clinical data are needed given the increasing national interest in charged particle radiation therapy (CPT) programs. Here we report long-term outcomes from the only randomized, stratified trial comparing CPT with iodine-125 plaque therapy for choroidal and ciliary body melanoma. Methods and Materials: From 1985 to 1991, 184 patients met eligibility criteria and were randomized to receive particle (86 patients) or plaque therapy (98 patients). Patients were stratified by tumor diameter, thickness, distance to disc/fovea, anterior extension, and visual acuity. Tumors close to the optic disc were included. Local tumor control, as well as eye preservation, metastases due to melanoma, and survival were evaluated. Results: Median follow-up times for particle and plaque arm patients were 14.6 years and 12.3 years, respectively (P=.22), and for those alive at last follow-up, 18.5 and 16.5 years, respectively (P=.81). Local control (LC) for particle versus plaque treatment was 100% versus 84% at 5 years, and 98% versus 79% at 12 years, respectively (log rank: P=.0006). If patients with tumors close to the disc (<2 mm) were excluded, CPT still resulted in significantly improved LC: 100% versus 90% at 5 years and 98% versus 86% at 12 years, respectively (log rank: P=.048). Enucleation rate was lower after CPT: 11% versus 22% at 5 years and 17% versus 37% at 12 years, respectively (log rank: P=.01). Using Cox regression model, likelihood ratio test, treatment was the most important predictor of LC (P=.0002) and eye preservation (P=.01). CPT was a significant predictor of prolonged disease-free survival (log rank: P=.001). Conclusions: Particle therapy resulted in significantly improved local control, eye preservation, and disease-free survival as confirmed by long-term outcomes from the only randomized study available to date comparing radiation modalities in choroidal and ciliary body melanoma.

  13. Protective effect of ciliary neurotrophic factor (CNTF) in a model of endotoxic shock: action mechanisms and role of CNTF receptor alpha. (United States)

    Demitri, M T; Benigni, F; Meazza, C; Zinetti, M; Fratelli, M; Villa, P; Acheson, A; Panayotatos, N; Ghezzi, P


    Ciliary neurotrophic factor (CNTF) inhibits the production of tumor necrosis factor (TNF) in lipopolysaccharide (LPS)-treated mice and protects against LPS lethality when coadministered with its soluble receptor (sCNTFR alpha). Both of these activities are abolished in adrenalectomized (ADX) mice. LPS-induced pulmonary polymorphonuclear neutrophil (PMN) infiltration and nitric oxide (NO) production were also inhibited by CNTF + sCNTFR alpha but not by CNTF alone. sCNTFR alpha did not alter the clearance or tissue distribution of CNTF. Furthermore, CNTF variants coadministered with sCNTFR alpha protected against LPS toxicity in a manner related to their affinity for the beta components of CNTFR. Thus, inhibition of TNF production and protection against LPS lethality by CNTF/sCNTFR alpha require an intact hypothalamus-pituitary-adrenal axis (HPAA) and may be mediated by endogenous glucocorticoids. This protective effect is, at least in part, due to the inhibition of PMN infiltration and NO production, and appears to be mediated by cells displaying only beta-receptor subtypes.

  14. Super-resolution imaging of ciliary microdomains in isolated olfactory sensory neurons using a custom two-color stimulated emission depletion microscope (United States)

    Meyer, Stephanie A.; Ozbay, Baris N.; Potcoava, Mariana; Salcedo, Ernesto; Restrepo, Diego; Gibson, Emily A.


    We performed stimulated emission depletion (STED) imaging of isolated olfactory sensory neurons (OSNs) using a custom-built microscope. The STED microscope uses a single pulsed laser to excite two separate fluorophores, Atto 590 and Atto 647N. A gated timing circuit combined with temporal interleaving of the different color excitation/STED laser pulses filters the two channel detection and greatly minimizes crosstalk. We quantified the instrument resolution to be ˜81 and ˜44 nm, for the Atto 590 and Atto 647N channels. The spatial separation between the two channels was measured to be under 10 nm, well below the resolution limit. The custom-STED microscope is incorporated onto a commercial research microscope allowing brightfield, differential interference contrast, and epifluorescence imaging on the same field of view. We performed immunolabeling of OSNs in mice to image localization of ciliary membrane proteins involved in olfactory transduction. We imaged Ca2+-permeable cyclic nucleotide gated (CNG) channel (Atto 594) and adenylyl cyclase type III (ACIII) (Atto 647N) in distinct cilia. STED imaging resolved well-separated subdiffraction limited clusters for each protein. We quantified the size of each cluster to have a mean value of 88±48 nm and 124±43 nm, for CNG and ACIII, respectively. STED imaging showed separated clusters that were not resolvable in confocal images.

  15. Control of ventricular ciliary beating by the Melanin Concentrating Hormone-expressing neurons of the lateral hypothalamus : a functional imaging survey.

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    Gregory eConductier


    Full Text Available The cyclic peptide Melanin-Concentrating Hormone (MCH is known to control a large number of brain functions in mammals such as food intake and metabolism, stress response, anxiety, sleep/wake cycle, memory and reward. Based on neuroanatomical and electrophysiological studies these functions were attributed to neuronal circuits expressing MCHR1, the single MCH receptor in rodents. In complement to our recently published work (Conductier et al. 2013 we provided here new data regarding the action of MCH on ependymocytes in the mouse brain. First, we establish that MCHR1 mRNA is expressed in the ependymal cells of the third ventricle epithelium. Second, we demonstated a tonic control of MCH-expressing neurons on ependymal cilia beat frequency using in vitro optogenics. Finally, we performed in vivo measurements of CSF flow using fluorescent micro-beads in wild-type and MCHR1 knockout mice. Collectively, our results demonstrated that MCH-expressing neurons modulate ciliary beating of ependymal cells at the third ventricle and could contribute to maintain cerebro-spinal fluid homeostasis.

  16. Caracterización morfoanatómica comparativa entre Aloe vera (L. Burm. F., Aloe arborescens Mill., Aloe saponaria Haw. y Aloe ciliaris Haw. (Aloeaceae

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    Stella Maris Carpano

    Full Text Available Aloe vera (L. Burm. F. (= Aloe barbadensis Miller conhecida como "a planta da imortalidade" no antigo Egito é utilizada em fitoterapia como humectante, antibacteriana, antifúngica, antiviral e antioxidante. Com a finalidade de contribuir para identificação da droga vegetal, foram realizados estudos morfoanatômicos da folha. A utilização de plantas com características terapêuticas reconhecidas determina que, por analogia, popularmente sejam utilizadas com a mesma finalidade outras espécies do mesmo gênero. Isto é o que ocorre com três espécies de Aloe spp., que se cultivam ou crescem acidentalmente na Argentina: A. arborescens Mill., A. saponaria Haw. e A. ciliaris Haw. (Aloaceae. Estabeleceram-se os caracteres morfoanatômicos de diagnóstico por microscopia óptica e microscopia eletrônica de varredura (apresentam-se desenhos e fotomicrografias dos mesmos. Obtiveram-se valores numéricos dos elementos histológicos de diagnóstico: magnitudes lineares e proporcionais. Realizaram-se reações histoquímicas de identificação dos princípios ativos para sua localização "in situ".

  17. Pyriculins A and B, two monosubstituted hex-4-ene-2,3-diols and other phytotoxic metabolites produced by Pyricularia grisea isolated from buffelgrass (Cenchrus ciliaris). (United States)

    Masi, Marco; Meyer, Susan; Górecki, Marcin; Mandoli, Alessandro; Di Bari, Lorenzo; Pescitelli, Gennaro; Cimmino, Alessio; Cristofaro, Massimo; Clement, Suzette; Evidente, Antonio


    Pyricularia grisea has been identified as a foliar pathogen on buffelgrass (Cenchrus ciliaris) in North America and was studied as a potential source of phytotoxins for buffelgrass control. Two monosubstituted hex-4-ene-2,3-diols, named pyriculins A and B, were isolated from its culture filtrate organic extract together with (10S,11S)-(-)-epipyriculol, trans-3,4-dihydro-3,4,8-trihydroxy-1(2H)-napthalenone, and (4S)-(+)-isosclerone. Pyriculins A and B were characterized by spectroscopic (essentially nuclear magnetic resonance [NMR], High-resolution electrospray ionization mass spectrometry [HRESIMS]) and chemical methods such as (4E)-1-(4-hydroxy-1,3-dihydroisobenzofuran-1-yl)hex-4-ene-2,3-diols. The relative and absolute configuration of these compounds was determined by a combination of spectroscopic (NMR, electronic circular dichroism [ECD]) and computational tools. When bioassayed in a buffelgrass coleoptile and radicle elongation test, (10S,11S)-(-)-epipyriculol proved to be the most toxic compound. Seed germination was much reduced and slowed with respect to the control and radicles failed to elongate. All five compounds delayed germination, but only (10S,11S)-(-)-epipyriculol was able to prevent radicle development of buffelgrass seedlings. It had no effect on coleoptile elongation, while the other four compounds caused significantly increased coleoptile development relative to the control. © 2017 Wiley Periodicals, Inc.

  18. Primary ciliary dyskinesia in the paediatric population: range and severity of radiological findings in a cohort of patients receiving tertiary care

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    Jain, K. [Department of Radiology, Royal Brompton and Harefield NHS Trust, London (United Kingdom); Padley, S.P.G. [Department of Radiology, Royal Brompton and Harefield NHS Trust, London (United Kingdom)], E-mail:; Goldstraw, E.J.; Kidd, S.J. [Department of Radiology, Royal Brompton and Harefield NHS Trust, London (United Kingdom); Hogg, C.; Biggart, E.; Bush, A. [Department of Paediatric Respiratory Medicine, Royal Brompton and Harefield NHS Trust, London (United Kingdom)


    Aim: To investigate the clinical range and severity of radiological findings in a cohort of patients with primary ciliary dyskinesia (PCD) receiving tertiary care. Materials and methods: The case notes and clinical test results of 89 children attending the paediatric respiratory disease clinic at our institution were retrospectively analysed. Demographic details including age at diagnosis and common presenting signs and symptoms were studied. Results of chest radiographs, microscopy, and high-resolution computed tomography (HRCT) for quantification of lung damage were analysed. Results: In a cohort of 89 children with PCD, a presentation chest radiograph was available in 62% of patients (n = 55), with all but one demonstrating changes of bronchial wall thickening. HRCT of the lungs, available in 26 patients, were scored using the system described by Brody et al. analysing five specific features of lung disease, including bronchiectasis, mucus plugging, peribronchial thickening, parenchymal changes of consolidation, and ground-glass density, and focal air-trapping in each lobe. Peribronchial thickening was observed using HRCT in 25 patients, while 20 patients had bronchiectasis. Severity scores were highest for the middle and the lingular lobes. Conclusion: The radiographic findings of the largest reported cohort of patients with PCD are presented, with associated clinical findings. Dextrocardia remains the commonest finding on chest radiography. HRCT demonstrates peribronchial thickening and bronchiectasis, which is most marked in the lower zones. Radiological scoring techniques developed for assessment of cystic fibrosis can also be applied for the assessment of disease severity in this patient population.

  19. Localization of functional receptor epitopes on the structure of ciliary neurotrophic factor indicates a conserved, function-related epitope topography among helical cytokines. (United States)

    Panayotatos, N; Radziejewska, E; Acheson, A; Somogyi, R; Thadani, A; Hendrickson, W A; McDonald, N Q


    By rational mutagenesis, receptor-specific functional analysis, and visualization of complex formation in solution, we identified individual amino acid side chains involved specifically in the interaction of ciliary neurotrophic factor (CNTF) with CNTFR alpha and not with the beta-components, gp130 and LIFR. In the crystal structure, the side chains of these residues, which are located in helix A, the AB loop, helix B, and helix D, are surface accessible and are clustered in space, thus constituting an epitope for CNTFR alpha. By the same analysis, a partial epitope for gp130 was also identified on the surface of helix A that faces away from the alpha-epitope. Superposition of the CNTF and growth hormone structures showed that the location of these epitopes on CNTF is analogous to the location of the first and second receptor epitopes on the surface of growth hormone. Further comparison with proposed binding sites for alpha- and beta-receptors on interleukin-6 and leukemia inhibitory factor indicated that this epitope topology is conserved among helical cytokines. In each case, epitope I is utilized by the specificity-conferring component, whereas epitopes II and III are used by accessory components. Thus, in addition to a common fold, helical cytokines share a conserved order of receptor epitopes that is function related.

  20. RPGR: Its role in photoreceptor physiology, human disease, and future therapies. (United States)

    Megaw, Roly D; Soares, Dinesh C; Wright, Alan F


    Mammalian photoreceptors contain specialised connecting cilia that connect the inner (IS) to the outer segments (OS). Dysfunction of the connecting cilia due to mutations in ciliary proteins are a common cause of the inherited retinal dystrophy retinitis pigmentosa (RP). Mutations affecting the Retinitis Pigmentosa GTPase Regulator (RPGR) protein is one such cause, affecting 10-20% of all people with RP and the majority of those with X-linked RP. RPGR is located in photoreceptor connecting cilia. It interacts with a wide variety of ciliary proteins, but its exact function is unknown. Recently, there have been important advances both in our understanding of RPGR function and towards the development of a therapy. This review summarises the existing literature on human RPGR function and dysfunction, and suggests that RPGR plays a role in the function of the ciliary gate, which controls access of both membrane and soluble proteins to the photoreceptor outer segment. We discuss key models used to investigate and treat RPGR disease and suggest that gene augmentation therapy offers a realistic therapeutic approach, although important questions still remain to be answered, while cell replacement therapy based on retinal progenitor cells represents a more distant prospect. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Morphology and accommodative function of the vitreous zonule in human and monkey eyes. (United States)

    Lütjen-Drecoll, Elke; Kaufman, Paul L; Wasielewski, Rainer; Ting-Li, Lin; Croft, Mary Ann


    To explore the attachments of the posterior zonule and vitreous in relation to accommodation and presbyopia in monkeys and humans. Novel scanning electron microscopy (SEM) and ultrasound biomicroscopy (UBM) techniques were used to visualize the anterior, intermediate, and posterior vitreous zonule and their connections to the ciliary body, vitreous membrane, lens capsule, and ora serrata, and to characterize their age-related changes and correlate them with loss of accommodative forward movement of the ciliary body. alpha-Chymotrypsin was used focally to lyse the vitreous zonule and determine the effect on movement of the accommodative apparatus in monkeys. The vitreous attached to the peripheral lens capsule and the ora serrata directly. The pars plana zonule and the posterior tines of the anterior zonule were separated from the vitreous membrane except for strategically placed attachments, collectively termed the vitreous zonule, that may modulate and smooth the forward and backward movements of the entire system. Age-dependent changes in these relationships correlated significantly with loss of accommodative amplitude. Lysis of the intermediate vitreous zonule partially restored accommodative movement. The vitreous zonule system may help to smoothly translate to the lens the driving forces of accommodation and disaccommodation generated by the ciliary muscle, while maintaining visual focus and protecting the lens capsule and ora serrata from acute tractional forces. Stiffening of the vitreous zonular system may contribute to age-related loss of accommodation and offer a therapeutic target for presbyopia.

  2. Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium. (United States)

    Amitani, R; Taylor, G; Elezis, E N; Llewellyn-Jones, C; Mitchell, J; Kuze, F; Cole, P J; Wilson, R


    The mechanisms by which Aspergillus fumigatus colonizes the respiratory mucosa are unknown. Culture filtrates of eight of nine clinical isolates of A. fumigatus slowed ciliary beat frequency and damaged human respiratory epithelium in vitro. These changes appeared to occur concurrently. Culture filtrates of two clinical isolates of Candida albicans had no effect on ciliated epithelium. We have purified and characterized cilioinhibitory factors of a clinical isolate of A. fumigatus. The cilioinhibitory activity was heat labile, reduced by dialysis, and partially extractable into chloroform. The activity was associated with both high- and low-molecular-weight factors, as determined by gel filtration on Sephadex G-50. A low-molecular-weight cilioinhibitory factor was further purified by reverse-phase high-performance liquid chromatography and shown by mass spectrometry to be gliotoxin, a known metabolite of A. fumigatus. Gliotoxin significantly slowed ciliary beat frequency in association with epithelial damage at concentrations above 0.2 microgram/ml; other Aspergillus toxins, i.e., fumagillin and helvolic acid, were also cilioinhibitory but at much higher concentrations. High-molecular-weight (> or = 35,000 and 25,000) cilioinhibitory materials had neither elastolytic nor proteolytic activity and remain to be identified. Thus, A. fumigatus produces a number of biologically active substances which slow ciliary beating and damage epithelium and which may influence colonization of the airways.

  3. [Ultrastructure of epithelium and ciliary receptors in the parasitic turbellarian Urastoma cyprinae (Turbellaria, "Prolecithophora") and position of the species within Platyhelminthes]. (United States)

    Kornakova, E E


    be the preadaptation to the endoparasitic mode of life in Fecampiida. The differencies in ultrastructure of epithelium in U. cyprinae from the White Sea and from Mediterranean Sea (Noury-Sraïri e. a., 1990) may be explained by the differences in the method of fixation or by the parasitizing the another host--the mollusk Mytilus galloprovincialis. The ciliary receptors of five types were revealed in U. cyprinae (fig. 3, e, [symbol: see text]; 4; 5; 6). They differ in the shape and length of the ciliary rootlets and in the content of the nerve processes. All receptors lack of the real collars typical for the receptors of Neodermata. Urastoma is most close to the Neodermata amond parasitic turbellarians studied thus far, and the absence of collars in receptors of this species testifies that the collars are the veritable synapomorphy of the Neodermata. The diversity in the ultrastructure and possible functions of receptors correspond to the complicated adaptations of this species. The modern molecular data as well as the ultrastructural evidence attest that parasitic turbellarians of the genera Urastoma, Genostoma and Ichthyophaga are relatives and cannot be included in any turbellarian order known. Therefore Urastoma, Genostoma and Ichthyophaga have been erected in the separate order Urastomida ord. nov. The diagnosis of the new order is given.

  4. Effects of Resistance Training on Muscle Strength, Endurance, and Motor Unit According to Ciliary Neurotrophic Factor Polymorphism in Male College Students

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    Ae-Rim Hong, Sang-Min Hong, Yun-A Shin


    Full Text Available Changes in muscle mass and strength across the adult age span are variable and related to the ciliary neurotrophic factor (CNTF genotype. In particular, a single CNTF haplotype (1357 G→A is important for neuronal and muscular developments and may be associated with muscle strength response to resistance training. We examined whether CNTF genotype differentially influences the effect of resistance training on neuromuscular improvement in male college students. Resistance training of the upper extremities comprised 3 sets at 75%–85% intensity per 1 repetition maximum, 3 times a week, for a total of 8 weeks. We measured isokinetic muscle function of the elbow joint with regard to strength (60°/s and endurance (180°/s by using an isokinetic dynamometer. The biceps brachii (BB and brachioradialis muscles were studied using surface electromyography with spike-triggered averaging to assess surface-detected motor unit potential (SMUP area. After resistance training, the SMUP of the BB increased significantly at 60°/s (p < 0.05, but no difference in the CNTF genotype was observed. The SMUP of the BB at 180°/s increased significantly in the GG/AA genotype group compared with that in the GA genotype group (p < 0.05. The average power of the elbow flexor at 180°/s increased significantly after resistance training (p < 0.05, but again, no difference in the CNTF genotype was observed. Thus, improvements in muscle strength and endurance may have resulted directly from resistance training rather than from genetic factors related to nerves in muscle tissue.

  5. Cochliotoxin, a Dihydropyranopyran-4,5-dione, and Its Analogues Produced by Cochliobolus australiensis Display Phytotoxic Activity against Buffelgrass (Cenchrus ciliaris). (United States)

    Masi, Marco; Meyer, Susan; Clement, Suzette; Cimmino, Alessio; Cristofaro, Massimo; Evidente, Antonio


    Buffelgrass (Pennisetum ciliare or Cenchrus ciliaris) is a perennial grass that has become highly invasive in the Sonoran Desert of southern Arizona. In the search for novel control strategies against this weed, strains of the foliar fungal pathogen Cochliobolus australiensis from buffelgrass have been screened for their ability to produce phytotoxic metabolites that could potentially be used as natural herbicides in an integrated pest management strategy. A new phytotoxin, named cochliotoxin, was isolated from liquid culture of this fungus together with radicinin, radicinol, and their 3-epimers. Cochliotoxin was characterized, essentially by spectroscopic methods, as 3-hydroxy-2-methyl-7-(3-methyloxiranyl)-2,3-dihydropyrano[4,3-b]pyran-4,5-dione. Its relative stereochemistry was assigned by 1 H NMR techniques, while the absolute configuration (2S,3S) was determined applying the advanced Mosher's method by esterification of its hydroxy group at C-3. When bioassayed in a buffelgrass coleoptile elongation test and by leaf puncture bioassay against the host weed and two nontarget grasses, cochliotoxin showed strong phytotoxicity. In the same tests, radicinin and 3-epi-radicinin also showed phytotoxic activity, while radicinol and 3-epi-radicinol were largely inactive. All five compounds were more active in leaf puncture bioassays on buffelgrass than on the nontarget grass tanglehead (Heteropogon contortus), while the nontarget grass Arizona cottontop (Digitaria californica) was more sensitive to radicinin and 3-epi-radicinin. Cochliotoxin at low concentration was significantly more active on buffelgrass than on either native grass, but the difference was small.

  6. Discinesia ciliar primária: quando o pediatra deve suspeitar e como diagnosticar? Primary ciliary dyskinesia: when the pediatrician must suspect and how to do the diagnosis?

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    Mary Anne K. Olm


    Full Text Available OBJETIVO: Revisar a discinesia ciliar primária (DCP quanto aos seus aspectos ultra-estruturais, discriminar os defeitos ciliares primários dos secundários, descrever o quadro clínico, os testes laboratoriais de triagem e de diagnóstico disponíveis, bem como seu manejo clínico. FONTE DE DADOS: Pesquisa nas bases de dados Medline, Lilacs e SciELO, no período de 1980 a 2007. SÍNTESE DOS DADOS: A DCP é uma doença autossômica recessiva que compromete a estrutura e/ou a função ciliar e, conseqüentemente, o transporte mucociliar. As manifestações clínicas envolvem o trato respiratório superior e inferior, com infecções recorrentes do ouvido médio, seios paranasais e pulmonares, que podem evoluir para bronquiectasias. Outras manifestações incluem situs inversus totalis e infertilidade masculina. O diagnóstico deve ser suspeitado pelos pediatras em várias situações: recém-nascidos de termo com desconforto respiratório sem causa aparente; neonatos portadores de dextrocardia; lactentes com tosse persistente e/ou infecções otorrinolaringológicas de repetição, excluindo-se as imunodeficiências e a fibrose cística; crianças com asma atípica e as com bronquiectasias sem causa definida. Os testes de triagem diagnóstica são os da sacarina e do óxido nítrico nasal. As avaliações do defeito ultra-estrutural e funcional exigem análise por microscopia eletrônica e da freqüência e formato da onda de batimento ciliar. CONCLUSÕES: A DCP, apesar da baixa prevalência, é pouco diagnosticada pelas dificuldades de estabelecer o diagnóstico definitivo do defeito ciliar devido à complexidade da investigação laboratorial e pela falta de reconhecimento da doença pelos médicos. A suspeita clínica e o diagnóstico precoce são fundamentais para reduzir a morbidade e prevenir o desenvolvimento de complicações.OBJECTIVE: To review primary ciliary dyskinesia (PCD and its ultrastructural aspects, to differentiate primary

  7. Studies on SO/sub 2/, NO/sub 2/ and NH/sub 3/: effect on ciliary activity in rabbit trachea of single in vitro exposure and resorption in rabbit nasal cavity

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    Dalhamm, T; Sjoeholm, J


    Absorption in nasal cavity was tested by drawing gas through tracheal cannula at 1 liter/min for 45 min (...simple and is not intended to give accurate quantitative results.). Both SO/sub 2/ and NH/sub 3/ were strongly absorbed, even at high concentrations, whereas NO/sub 2/ was not. Required concentration to arrest ciliary activity after 5 min was 500 to 1000 mg/liter for NH/sub 3/, 150 to 200 for NO/sub 2/, and 20 to 30 for SO/sub 2/. Some evidence of dose-time-effect for this action was observed.

  8. A new index for characterizing micro-bead motion in a flow induced by ciliary beating: Part II, modeling.

    Directory of Open Access Journals (Sweden)

    Mathieu Bottier


    Full Text Available Mucociliary clearance is one of the major lines of defense of the human respiratory system. The mucus layer coating the airways is constantly moved along and out of the lung by the activity of motile cilia, expelling at the same time particles trapped in it. The efficiency of the cilia motion can experimentally be assessed by measuring the velocity of micro-beads traveling through the fluid surrounding the cilia. Here we present a mathematical model of the fluid flow and of the micro-beads motion. The coordinated movement of the ciliated edge is represented as a continuous envelope imposing a periodic moving velocity boundary condition on the surrounding fluid. Vanishing velocity and vanishing shear stress boundary conditions are applied to the fluid at a finite distance above the ciliated edge. The flow field is expanded in powers of the amplitude of the individual cilium movement. It is found that the continuous component of the horizontal velocity at the ciliated edge generates a 2D fluid velocity field with a parabolic profile in the vertical direction, in agreement with the experimental measurements. Conversely, we show than this model can be used to extract microscopic properties of the cilia motion by extrapolating the micro-bead velocity measurement at the ciliated edge. Finally, we derive from these measurements a scalar index providing a direct assessment of the cilia beating efficiency. This index can easily be measured in patients without any modification of the current clinical procedures.



    Efstathios T. Detorakis; Eleni E. Drakonaki; Harilaos Ginis; Nikolaos Karyotakis; Ioannis G. Pallikaris


    Introduction: A previous study has employed shear-wave ultrasound elastographic imaging to assess corneal rigidity in an ex-vivo porcine eye model. This study employs the same modality in vivo in a rabbit eye model in order to assess lens, ciliary body and total ocular rigidity changes following the instillation of atropine and pilocarpine. Methods: Ten non-pigmented female rabbits were examined. Measurements of the lens, ciliary body and total ocular rigidity as well as lens thickness and an...

  10. Ciliary neurotrophic factor inhibits brain and peripheral tumor necrosis factor production and, when coadministered with its soluble receptor, protects mice from lipopolysaccharide toxicity. (United States)

    Benigni, F; Villa, P; Demitri, M T; Sacco, S; Sipe, J D; Lagunowich, L; Panayotatos, N; Ghezzi, P


    The receptor of ciliary neurotrophic factor (CNTF) contains the signal transduction protein gp130, which is also a component of the receptors of cytokines such as interleukin (IL)-6, leukemia-inhibitory factor (LIF), IL-11, and oncostatin M. This suggests that these cytokines might share common signaling pathways. We previously reported that CNTF augments the levels of corticosterone (CS) and of IL-6 induced by IL-1 and induces the production of the acute-phase protein serum amyloid A (SAA). Since the elevation of serum CS is an important feedback mechanism to limit the synthesis of proinflammatory cytokines, particularly tumor necrosis factor (TNF), we have investigated the effect of CNTF on both TNF production and lipopolysaccharide (LPS) toxicity. To induce serum TNF levels, LPS was administered to mice at 30 mg/kg i.p. and CNTF was administered as a single dose of 10 micrograms/mouse i.v., either alone or in combination with its soluble receptor sCNTFR alpha at 20 micrograms/mouse. Serum TNF levels were the measured by cytotoxicity on L929 cells. In order to measure the effects of CNTF on LPS-induced TNF production in the brain, mice were injected intracerebroventricularly (i.c.v.) with 2.5 micrograms/kg LPS. Mouse spleen cells cultured for 4 hr with 1 microgram LPS/ml, with or without 10 micrograms CNTF/ml, were also analyzed for TNF production. CNTF, administered either alone or in combination with its soluble receptor, inhibited the induction of serum TNF levels by LPS. This inhibition was also observed in the brain when CNTF and LPS were administered centrally. In vitro, CNTF only marginally affected TNF production by LPS-stimulated mouse splenocytes, but it acted synergistically with dexamethasone (DEX) in inhibiting TNF production. Most importantly, CNTF administered together with sCNTFR alpha protected mice against LPS-induced mortality. These data suggest that CNTF might act as a protective cytokine against TNF-mediated pathologies both in the brain and

  11. Methylopila capsulata gen. nov., sp. nov., a novel non-pigmented aerobic facultatively methylotrophic bacterium. (United States)

    Doronina, N V; Trotsenko, Y A; Krausova, V I; Boulygina, E S; Tourova, T P


    A new genus, Methylopila, and one new species are described for a group of seven strains of facultatively methylotrophic bacteria with the serine pathway of C1 assimilation. These bacteria are aerobic, Gram-negative, non-spore--forming, motile, colourless rods that multiply by binary fission. Their DNA base content ranges from 66 to 70 mol % G + C. Their cellular fatty acid profile consists primarily of C18:1 omega 7 cis-vaccenic and C19:0 cyclopropane acids. The major hydroxy acid is 3-OH C14:0. The main ubiquinone is Q-10. The dominant cellular phospholipids are phosphatidylethanolamine and phosphatidylcholine. The new isolates have a low level of DNA-DNA homology (5-10%) with the type strains of the serine pathway methylobacteria belonging to the genera Methylobacterium, Aminobacter, Hyphomicrobium and Methylorhabdus. Another approach, involving 16S rRNA gene sequence analysis of strain IM1T, has shown that the new isolates represent a separate branch within the alpha-2 subclass of the Proteobacteria. The type species of the new genus is Methylopila capsulata sp. nov., with the type strain IM1T (= VKM B-1606T).

  12. Non pigmenting mucosal fixed drug eruption due to tadalafil: A report of two cases

    Directory of Open Access Journals (Sweden)

    Sudip Das


    Full Text Available Various ′sex-stimulant′ medicines with fancy names and attractive packaging are available over the counter. Most contain phosphodiesterase 5 inhibitors in various strengths, often with herbal additions. These drugs are used erratically by the lay public, driven by folklore that such usage leads to increase in the length, girth or firmness of the penis. Such indiscriminate use by an otherwise healthy population leads to undue side effects.

  13. Differential sensitivity of pigmented and non-pigmented marine bacteria to metals and antibiotics

    Digital Repository Service at National Institute of Oceanography (India)

    Nair, S.; Chandramohan, D.; LokaBharathi, P.A.

    . Appl. em'ir. Microbiol. 33, 975-976. Nelson J. D. Jr and Colwell R. R. (1975) The ecology of mercury resistant bacteria in Chesapeake bay. Microbioi. Ecol. 1, 191-218. Oison B. H. and Thornton I. (1982) The resistance patterns to metals... to metals em- ploying epifluorescent microscopy. J. microbiol. Met& 7, 143-155. Zemelman R., Silva J. and Herriques, M. (1980) Antibiotic resistant bacteria in seawater from Concepcion Bay. Archs Biol. Exp. 13, 121. ...

  14. Nueva variante de abordaje al surco ciliar en la fijación transescleral de lentes de cámara posterior New variant of approach to the ciliary sulcus in the transcleral fixation of posterior chamber lens

    Directory of Open Access Journals (Sweden)

    Ileana Vila Dópico


    Full Text Available Se expone una variante de abordaje al surco ciliar para la fijación del lente intraocular de cámara posterior, que está a nuestro alcance, en pacientes en que no existe soporte capsular o este es insuficiente. Se describe la técnica. Se realizó en 17 pacientes de los que se obtuvo mejoría visual en todos los casos (20/50-20/20 con un seguimiento promedio de 12 meses. Esta variante tiene la ventaja de evitar el paso de la aguja por el surco ciliar a ciegas, pues se utiliza el abordaje a través de la esclera y con ello evitamos dañar estructuras oculares aledañas evitando el riesgo de complicaciones por lo que se logra la recuperación anatómica y funcional en todos los casos.A variant to approach the ciliary sulcus for fixating the posterior chamber intraocular lens, which is within our reach, in patients with insufficient or no capsular support, is explained. The technique is described here and it was applied to 17 patients. Visual improvement was obtained in all cases (20/50-20/20 with an average follow-up of 12 months. This variant allows to prevent the blind passage of the needle through the ciliary sulcus, since it is approached via the sclera, avoiding to damage adjoining ocular structures and to have complications, and making possible the anatomic and functional recovery of all patients.

  15. Neovascular glaucoma in a child: an unusual presentation of medulloepithelioma

    Directory of Open Access Journals (Sweden)

    Kassa, Enoch


    Full Text Available [english] A healthy 12 month old infant without significant medical history presented with left eye redness for one week. Ophthalmic examination showed elevated intraocular pressure with iris neovascularization in the affected eye with increased optic nerve cupping. Scleral depression revealed a ciliary body mass in the supratemporal quadrant. A large, non-pigmented, vascular mass was noted; biopsy results showed multilayered cords, tubules, and sheets resembling primitive medullary epithelium arising from the ciliary body. The patient was diagnosed with medulloepithelioma. The patient underwent enucleation of the affected eye. Medulloepithelioma is a rare but important cause of neovascular glaucoma in the pediatric population. This case will focus on the characteristics of medulloepthelioma and the differential diagnosis for a non-pigmented ciliary body mass in a child.

  16. Cistos primários do epitélio pigmentar da íris e corpo ciliar: aspectos de biomicroscopia ultra-sônica Primary cysts of the iris and ciliary body pigment epithelium: ultrasound biomicroscopy features

    Directory of Open Access Journals (Sweden)

    Bernadete Ayres


    Full Text Available Objetivo: Descrever as características, incidência e distribuição dos cistos primários de epitélio pigmentar de íris e corpo ciliar ao exame de biomicroscopia ultra-sônica, que devem ser diferenciados de lesões sólidas. Métodos: Foram estudados de modo retrospectivo os prontuários de 73 pacientes, 82 olhos, com diagnóstico ecográfico de cisto primário de íris ou corpo ciliar durante o período de janeiro/97 a dezembro/99. Utilizou-se o biomicroscópio ultra-sônico, aplicando técnicas padronizadas de imersão. Resultados: À biomicroscopia ultra-sônica os cistos caracterizaram-se por apresentarem paredes finas e regulares, e conteúdo anecóico. Quarenta e oito pacientes (65,7% eram do sexo feminino. A maior incidência (28,8% ocorreu para o grupo incluído no intervalo de 20 a 29 anos de idade. Observou-se uma característica distribuição, predominantemente nos quadrantes temporais inferiores. Conclusões: A biomicroscopia ultra-sônica mostrou-se útil no diagnóstico de cistos primários do epitélio pigmentar da íris e do corpo ciliar, auxiliando na diferenciação de patologias tumorais e avaliando possíveis complicações. O conhecimento dos critérios ecográficos e da distribuição epidemiológica facilitam o diagnóstico destas lesões.Purpose: To describe the ultrasound biomicroscopic characteristics, incidence, distribution and location of primary cysts of the iris and ciliary body pigment epithelium, and to differentiate them from solid lesions. Methods: A retrospective study was performed through a review of charts of 73 patients, 82 eyes, with echographic diagnosis of primary cysts of the iris and ciliary body pigment epithelium during a 36-month period (January/97 through December/99. All examinations were performed using an ultrasound biomicroscope applying standard immersion techniques. Results: Ultrasound biomicroscopy revealed typical findings of the primary cysts of the pigment epithelium such as thin

  17. Discinesia ciliar primária: considerações sobre seis casos da síndrome de Kartagener Primary ciliary dyskinesia: considerations regarding six cases of Kartagener syndrome

    Directory of Open Access Journals (Sweden)

    Hugo Alejandro Vega Ortega


    Full Text Available A discinesia ciliar primária (DCP, anteriormente conhecida como síndrome dos cílios imóveis, é uma doença hereditária autossômica recessiva que inclui vários padrões de defeitos em sua ultra-estrutura ciliar. Sua forma clínica mais grave é a síndrome de Kartagener (SK, a qual é encontrada em 50% dos casos de DCP. A DCP causa deficiência ou mesmo estase no transporte de secreções em todo o trato respiratório, favorecendo a proliferação de vírus e bactérias. Sua incidência varia de 1:20.000 a 1:60.000. Como conseqüência, os pacientes apresentam infecções crônicas e repetidas desde a infância e geralmente são portadores de bronquite, pneumonia, hemoptise, sinusite e infertilidade. As bronquiectasias e outras infecções crônicas podem ser o resultado final das alterações irreversíveis dos brônquios, podendo progredir para cor pulmonale crônico e suas conseqüências. Somente a metade dos pacientes afetados pela DCP apresenta todos os sintomas, condição denominada SK completa; no restante, não ocorre situs inversus, condição denominada SK incompleta. O diagnóstico é feito com base no quadro clínico e confirmado por meio da microscopia eletrônica de transmissão. Como não há tratamento especifico para a DCP, recomenda-se que, tão logo seja feito o diagnóstico, as infecções secundárias sejam tratadas com antibióticos potentes e medidas profiláticas sejam adotadas. Neste trabalho, relatamos seis casos de DCP (cinco casos de SK completa e um caso de SK incompleta e revisamos a literatura sobre o assunto, tendo como foco os aspectos diagnósticos, terapêuticos e clínicos desta doença.Primary ciliary dyskinesia (PCD, previously known as immotile cilia syndrome, is an autosomal recessive hereditary disease that includes various patterns of ciliary ultrastructural defects. The most serious form is Kartagener syndrome (KS, which accounts for 50% of all cases of PCD. The incidence of PCD ranges from 1

  18. Métodos comparativos para recomposição de áreas de mata ciliar avaliados por análise longitudinal = Comparative methods for ciliary forest rearrangement evaluated by longitudinal analysis

    Directory of Open Access Journals (Sweden)

    Alessandra Costa Carrito Bobato


    Full Text Available Foram avaliados três métodos de distribuição de mudas para recomposição artificial de área de mata ciliar estudando-se a variação do crescimento da estatura e diâmetro durante seis períodos em um ano, das espécies Schinus terbinthifolia Raddi–aroeira ePeltophorum dubium Taub–canafístula. Os métodos estudados foram: mudas distribuídas ao acaso em espaçamento de 2 x 2 m; mudas distribuídas individualmente ao acaso; mudas distribuídas ao acaso em agrupamento três a três, com espaçamento de 1 a 1,5 m. O crescimento da estatura e do diâmetro das espécies estudadas está diretamente relacionado com os períodos em estudo, o tratamento de recomposição e as espécies. O tratamento mudas distribuídas ao acaso individualmente foi o que apresentou melhor crescimento médio do diâmetro.This trial aimed at evaluating three methods to distribute seedlingsfrom Schinus terbinthifolia and Peltophorum dubium species for rearrangement of ciliary forests. Their growth changes in height and diameter were used as parameters during six terms in one year. The studied methods were: seedlings randomized distributed in 2 x 2 m; seedlings individually distributed in a randomized design and seedlings randomized distributed in groups by three, using a 1 to 1.5 m row distance. The growth regarding diameter and height of the observed species is straightly related to the studied periods, rearrangement treatment and species. As a conclusion, it was registered that the seedling treatment individually distributed in a randomized design was the best answer regarding the average growth ofdiameter.

  19. Determination of the optical properties of melanin-pigmented human skin equivalents using terahertz time-domain spectroscopy (United States)

    Lipscomb, Dawn; Echchgadda, Ibtissam; Peralta, Xomalin G.; Wilmink, Gerald J.


    Terahertz time-domain spectroscopy (THz-TDS) methods have been utilized in previous studies in order to characterize the optical properties of skin and its primary constituents (i.e., water, collagen, and keratin). However, similar experiments have not yet been performed to investigate whether melanocytes and the melanin pigment that they synthesize contribute to skin's optical properties. In this study, we used THz-TDS methods operating in transmission geometry to measure the optical properties of in vitro human skin equivalents with or without normal human melanocytes. Skin equivalents were cultured for three weeks to promote gradual melanogenesis, and THz time domain data were collected at various time intervals. Frequency-domain analysis techniques were performed to determine the index of refraction (n) and absorption coefficient (μa) for each skin sample over the frequency range of 0.1-2.0 THz. We found that for all samples as frequency increased, n decreased exponentially and the μa increased linearly. Additionally, we observed that skin samples with higher levels of melanin exhibited greater n and μa values than the non-pigmented samples. Our results indicate that melanocytes and the degree of melanin pigmentation contribute in an appreciable manner to the skin's optical properties. Future studies will be performed to examine whether these contributions are observed in human skin in vivo.

  20. A relação entre o comprimento dos processos ciliares medidos pela biomicroscopia ultra-sônica e a duração, localização e gravidade das uveítes The relationship between the length of ciliary processes as measured by ultrasound biomicroscopy and the duration, localization and severity of uveitis

    Directory of Open Access Journals (Sweden)

    Daniella Socci da Costa


    Full Text Available OBJETIVO: Determinar a relação entre o comprimento dos processos ciliares com a duração, localização e gravidade das uveítes. MÉTODOS: Foram analisados em estudo prospectivo, 58 indivíduos, incluindo pacientes com diferentes estágios de uveíte e indivíduos sem a doença (112 olhos, sendo 18 normais, no período de agosto de 2001 a agosto de 2002, no Departamento de Uveítes do Cole Eye Institute da Cleveland Clinic Foundation - Ohio - EUA. Todos os pacientes foram referidos para o exame de biomicroscopia ultra-sônica, pelo Departamento de Uveítes após exame oftalmológico de rotina. O aparelho modelo 840 (Zeiss-Humphrey com transdutor de 50 MHz foi utilizado para análise dos processos ciliares sob anestesia tópica e técnica de imersão. RESULTADOS: Em relação à etiologia das uveítes, a de maior freqüência foi a idiopática (27,8%. As uveítes recorrentes, agressivas e difusas levaram ao significante dano nos processos ciliares. A maior perda significativa na medida dos processos ciliares foi encontrada no quadrante inferior e as maiores medidas foram encontradas em olhos normais e no quadrante temporal. CONCLUSÃO: A biomicroscopia ultra-sônica mostrou ser método útil para avaliar as alterações anatômicas encontradas nos processos ciliares dos pacientes com uveíte. De acordo com estes achados, podemos criar recomendações para futuros trabalhos, que nos ajudem a avaliar a necessidade destes pacientes vir a receber tratamento mais agressivo em qualquer sinal de inflamação, com o objetivo de prevenir futuro dano e eventual hipotonia.PURPOSE: To determine the relationship between the length of ciliary processes as measured by ultrasound biomicroscopy and the duration, localization and severity of uveitis. METHODS: We analyzed in this prospective study, 58 individuals including patients with different stages of uveitis and normal patients (112 eyes including 18 normal, between August 2001 and August 2002, at the

  1. Methylobacillus pratensis sp. nov., a novel non-pigmented, aerobic, obligately methylotrophic bacterium isolated from meadow grass. (United States)

    Doronina, Nina V; Trotsenko, Yuri A; Kolganova, Tatjana V; Tourova, Tatjana P; Salkinoja-Salonen, Mirja S


    Strain F31T was isolated from meadow grass (Poa trivialis L.) sampled from the city park in Helsinki. Analysis of phenotypic and genotypic properties showed the strain to be related to the group of obligately methylotrophic non-methane utilizing bacteria (methylobacteria) with the ribulose monophosphate pathway of formaldehyde assimilation. Phylogenetic analysis showed the strain to be closely related to the genus Methylobacillus, and analysis of fatty acid composition confirmed this association. Thus, on the basis of its genotypic and phenotypic properties, the isolate is proposed as a novel species of the genus Methylobacillus, Methylobacillus pratensis sp. nov., with F31T as the type strain (= VKM B-2247T = NCIMB 13994T).

  2. Sudden death of an Indian peafowl (Pavo cristatus) at a zoo due to non-pigmented Serratia marcescens infection. (United States)

    Lee, Seung-Hun; Park, Sang-Joon; Kwak, Dongmi; Kim, Kyoo-Tae


    A 16-year-old female Indian peafowl (Pavo cristatus) died two days after recognition of conjunctivitis in the right eye, anorexia and depression. Gross necropsy revealed a thick pseudomembrane under the eyelid and hydropericardium. Histopathological examination revealed hepatocellular necrosis, sinusoidal and vascular congestion and infiltrated inflammatory cells. Infiltration by inflammatory cells was noted in the epicardium. The lungs had mild interstitial pneumonia with the extensive congestion within the capillaries of the air sacs. Tubular interstitial congestion and necrosis was noted in the kidneys. Bacterial culture and nucleotide sequencing of the inflammatory specimens identified the causative agent as Serratia marcescens, an uncommon bacterium in birds. In summary, this study describes the sudden death of an Indian peafowl due to S. marcescens infection, which is rarely seen in animals.

  3. Phenolic compounds and antioxidant capacity in different-colored and non-pigmented berries of bilberry (Vaccinium myrtillus L.)

    Czech Academy of Sciences Publication Activity Database

    Colak, N.; Primetta, A. K.; Riihinen, K. R.; Jaakola, L.; Grúz, Jiří; Strnad, Miroslav; Torun, H.; Ayaz, F. A.


    Roč. 20, DEC (2017), s. 67-78 ISSN 2212-4292 Institutional support: RVO:61389030 Keywords : Anthocyanin * Antioxidant * Bilberry * Phenolic acid * Vaccinium myrtillus Subject RIV: EF - Botanics OBOR OECD: Plant sciences, botany Impact factor: 1.964, year: 2016

  4. Expression and localization of the progesterone receptor in mouse and human reproductive organs

    DEFF Research Database (Denmark)

    Teilmann, Stefan Cuoni; Clement, Christian Alexandro; Thorup, Jørgen


    examined, primary granulosa cell cilia lacked PR staining. SDS-PAGE and western blotting analysis of tissues from oviduct, uterus, and ovary confirmed antibody specificity, and identified two bands corresponding to the PR isoforms PR-A and PR-B. Upon hCG stimulation, a new band cross-reacting with anti......-PR emerged above the PR-A form in oviduct fractions, suggesting LH-induced phosphorylation of PR-A. We suggest that ciliary PR in the oviduct plays a role in progesterone signaling after ovulation, possibly via non-genomic events. These novel findings warrant further studies of oviduct and postovulatory...... were unstained or faintly stained. Pubertal female mice were further studied by confocal laser scanning microscopy and western blotting before and after injection with FSH and LH followed by human chorionic gonadotropin (hCG) injection after a 48-h period. PR immunolocalization to the oviduct cilia...

  5. Porphyromonas pasteri sp. nov., isolated from human saliva. (United States)

    Sakamoto, Mitsuo; Li, Dan; Shibata, Yukie; Takeshita, Toru; Yamashita, Yoshihisa; Ohkuma, Moriya


    A bacterial strain, designated KUFDS01T, isolated from human saliva was characterized using a polyphasic taxonomic approach that included analysis of physiological and biochemical features, cellular fatty acid profiles and phylogenetic position based on 16S rRNA gene sequence analysis. Cells of the strain were obligately anaerobic, non-pigmented, non-spore-forming, non-motile, Gram-stain-negative rods. Growth of the strain was inhibited on medium containing 20% bile. The 16S rRNA gene sequence analysis showed that the strain was a member of the genus Porphyromonas. Strain KUFDS01T was closely related to Porphyromonas catoniae JCM 13863T (96.6% sequence similarity). An hsp60 gene sequence analysis indicated that strain KUFDS01T was different from P. catoniae JCM 13863T, with a sequence similarity value of 87.8%. The major cellular fatty acids of strain KUFDS01T were C16 : 0, iso-C15 : 0, anteiso-C15 : 0, C18 : 2ω6, 9c and C18 : 1ω9c. The DNA G+C content of strain KUFDS01T was 57.7 ± 0.66 mol%. On the basis of these data, strain KUFDS01T represents a novel species of the genus Porphyromonas, for which the name Porphyromonas pasteri sp. nov. is proposed. The type strain of P. pasteri is KUFDS01T ( = JCM 30531T = CCUG 66735T).

  6. Mutations in LRRC50 predispose zebrafish and humans to seminomas.

    Directory of Open Access Journals (Sweden)

    Sander G Basten


    Full Text Available Seminoma is a subclass of human testicular germ cell tumors (TGCT, the most frequently observed cancer in young men with a rising incidence. Here we describe the identification of a novel gene predisposing specifically to seminoma formation in a vertebrate model organism. Zebrafish carrying a heterozygous nonsense mutation in Leucine-Rich Repeat Containing protein 50 (lrrc50 also called dnaaf1, associated previously with ciliary function, are found to be highly susceptible to the formation of seminomas. Genotyping of these zebrafish tumors shows loss of heterozygosity (LOH of the wild-type lrrc50 allele in 44.4% of tumor samples, correlating with tumor progression. In humans we identified heterozygous germline LRRC50 mutations in two different pedigrees with a family history of seminomas, resulting in a nonsense Arg488* change and a missense Thr590Met change, which show reduced expression of the wild-type allele in seminomas. Zebrafish in vivo complementation studies indicate the Thr590Met to be a loss-of-function mutation. Moreover, we show that a pathogenic Gln307Glu change is significantly enriched in individuals with seminoma tumors (13% of our cohort. Together, our study introduces an animal model for seminoma and suggests LRRC50 to be a novel tumor suppressor implicated in human seminoma pathogenesis.

  7. On ciliary pumping and sieving in bryozoans

    DEFF Research Database (Denmark)

    Larsen, Poul Scheel; Riisgård, H. U.


    to be transferred to and conveyed by the frontal cilia bands on tentacles. The added load on laterofrontal cilia from viscous drag on a food particle retained by the cilia is found to be of the same order of magnitude or greater than the "background load" of viscous drag from fluid passing the laterofrontal cilia...... flicks, a description is given of the feeding mechanisms. Particles entering the central region are brought to the mouth by the high velocity feeding current in the central part of the lophophore. Particles entering further out either escape between tentacles or are stopped by the laterofrontal cilia...... sieve and, in the distal region of tentacles, are brought back into the central feeding current by flicks of tentacles. The relative velocity between fluid and particle during a flick recovery phase ensures particle release. Particles stopped in the proximal region of the lophophore appear...

  8. The intraflagellar transport machinery in ciliary signaling

    DEFF Research Database (Denmark)

    Mourão, André; Christensen, Søren Tvorup; Lorentzen, Esben


    Cilia and flagella on eukaryotic cells are slender microtubule-based projections surrounded by a membrane with a unique lipid and protein composition. It is now appreciated that cilia in addition to their established roles in motility also constitute hubs for cellular signaling by sensing external...

  9. An essential role of intestinal cell kinase in lung development is linked to the perinatal lethality of human ECO syndrome (United States)

    Tong, Yixin; Park, So Hyun; Wu, Di; Xu, Wenhao; Guillot, Stacey J.; Jin, Li; Li, Xudong; Wang, Yalin; Lin, Chyuan-Sheng; Fu, Zheng


    Human endocrine-cerebro-osteodysplasia (ECO) syndrome, caused by the loss-of-function mutation R272Q in the ICK (intestinal cell kinase) gene, is a neonatal-lethal developmental disorder. To elucidate the molecular basis of ECO syndrome, we constructed an Ick R272Q knock-in mouse model that recapitulates ECO pathological phenotypes. Newborns bearing Ick R272Q homozygous mutations die at birth due to respiratory distress. Ick mutant lungs exhibit not only impaired branching morphogenesis associated with reduced mesenchymal proliferation, but also significant airspace deficiency in primitive alveoli concomitant with abnormal interstitial mesenchymal differentiation. ICK dysfunction induces elongated primary cilia and perturbs ciliary Hedgehog signaling and autophagy during lung sacculation. Our study identifies an essential role for ICK in lung development and advances the mechanistic understanding of ECO syndrome. PMID:28380258

  10. Chemistry, distribution, and metabolism of tomato carotenoids and their impact on human health. (United States)

    Khachik, Frederick; Carvalho, Lorena; Bernstein, Paul S; Muir, Garth J; Zhao, Da-You; Katz, Nikita B


    Recent epidemiological studies have suggested that the consumption of tomatoes and tomato-based food products reduce the risk of prostate cancer in humans. This protective effect has been attributed to carotenoids, which are one of the major classes of phytochemicals in this fruit. The most abundant carotenoid in tomato is lycopene, followed by phytoene, phytofluene, zeta-carotene, gamma-carotene, beta-carotene, neurosporene, and lutein. The distribution of lycopene and related carotenoids in tomatoes and tomato-based food products has been determined by extraction and high-performance liquid chromatography-UV/Visible photodiode array detection. Detailed qualitative and quantitative analysis of human serum, milk, and organs, particularly prostate, have revealed the presence of all the aforementioned carotenoids in biologically significant concentrations. Two oxidative metabolites of lycopene, 2,6-cyclolycopene-1,5-diols A and B, which are only present in tomatoes in extremely low concentrations, have been isolated and identified in human serum, milk, organs (liver, lung, breast, liver, prostate, colon) and skin. Carotenoids may also play an important role in the prevention of age-related macular degeneration, cataracts, and other blinding disorders. Among 25 dietary carotenoids and nine metabolites routinely found in human serum, mainly (3R,3'R,6'R)-lutein, (3R,3'R)-zeaxanthin, lycopene, and their metabolites were detected in ocular tissues. In this review we identified and quantified the complete spectrum of carotenoids from pooled human retinal pigment epithelium, ciliary body, iris, lens, and in the uveal tract and in other tissues of the human eye to gain a better insight into the metabolic pathways of ocular carotenoids. Although (3R,3'R,6'R)-lutein, (3R,3'R)-zeaxanthin, and their metabolites constitute the major carotenoids in human ocular tissues, lycopene and a wide range of dietary carotenoids have been detected in high concentrations in ciliary body and

  11. [The Usher Syndrome, a Human Ciliopathy]. (United States)

    Wolfrum, Uwe; Nagel-Wolfrum, Kerstin


    The human Usher syndrome (USH) is a complex, rare disease manifesting in its most common form of inherited deaf-blindness. Due to the heterogeneous manifestation of the clinical symptoms, three clinical types (USH1-3) are distinguished according to the severity of the disease pattern. For a correct diagnosis, in addition to the auditory tests in early newborn screening, ophthalmological examinations and molecular genetic analysis are important. Ten known USH genes encode proteins, which are from heterogeneous protein families, interact in functional protein networks. In the eye and in the ear, USH proteins are expressed primarily in the mechano-sensitive hair cells and the rod and cone photoreceptor cells, respectively. In the hair cells, the USH protein networks are essential for the correct differentiation of the hair bundles as well as for the function of the mechano-electrical transduction complex in the matured cell. In the photoreceptor cells, USH proteins are located in the ciliary region and participate in intracellular transport processes. In addition, a USH protein network is present in the so-called calyceal processes. The lack of calyceal processes and the absence of a prominent visual phenotype in the mouse disqualifies mice as models for studies on the ophthalmic component of USH. While hearing impairments can be compensated with hearing aids and cochlear implants, there is no practical therapy for USH in the eye. Currently, gene-based therapy concepts, such as gene addition, applications of antisense oligonucleotides and TRIDs ("translational readthrough inducing drugs") for the readthrough of nonsense mutations are preclinically evaluated. For USH1B/MYO7A the UshStat gene therapy clinical trial is ongoing. Georg Thieme Verlag KG Stuttgart · New York.

  12. More Human than Human. (United States)

    Lawrence, David


    Within the literature surrounding nonhuman animals on the one hand and cognitively disabled humans on the other, there is much discussion of where beings that do not satisfy the criteria for personhood fit in our moral deliberations. In the future, we may face a different but related problem: that we might create (or cause the creation of) beings that not only satisfy but exceed these criteria. The question becomes whether these are minimal criteria, or hierarchical, such that those who fulfill them to greater degree should be afforded greater consideration. This article questions the validity and necessity of drawing divisions among beings that satisfy the minimum requirements for personhood; considering how future beings-intelligent androids, synthezoids, even alternate-substrate sentiences-might fit alongside the "baseline" human. I ask whether these alternate beings ought to be considered different to us, and why this may or may not matter in terms of a notion of "human community." The film Blade Runner, concerned in large part with humanity and its key synthezoid antagonist Roy Batty, forms a framing touchstone for my discussion. Batty is stronger, faster, more resilient, and more intelligent than Homo sapiens. His exploits, far beyond the capability of normal humans, are contrasted with his frailty and transient lifespan, his aesthetic appreciation of the sights he has seen, and his burgeoning empathy. Not for nothing does his creator within the mythos term him "more human than human."

  13. Comparative cyto-histological study of needle tip aspirates and entry sites after intravitreal injection using different needle types.

    Directory of Open Access Journals (Sweden)

    Lyubomyr Lytvynchuk

    Full Text Available A comparison of the cellular content of needle tip aspirates and entry sites after transconjunctival intravitreal injection (IVI using different needle types was performed. White outbred rats and human cadaver eyes were used for IVI by hypodermic 27 gauge (G and 30G needles, and spinal anesthesia Pencan 27G needles. Aspiration of vitreous for quantitative morphological and cell cultivation analysis, as well as cyto-histological analysis of aspirates and entry sites were carried out. The most common cells in the aspirates from all needle types were conjunctival epithelial-, ciliary body non-pigmented epithelial- and sclerocyte-like cells and granular proteins. Crystallized vitreous specimens were present in each aspirate. The entry sites of hypodermic needles showed marked trauma in all wall layers of rat and human eyes accompanied by cellular destruction and hemorrhages. Pencan 27G needle caused less tissue trauma with partial reposition of sclerocytes. Transconjunctival IVIs with hypodermic 27G and 30G, and Pencan 27G needles result in trauma of all layers of the eyeball. The possible consequences of cellular content being cut and injected into the eye, as well as the entry site wound shape deserve future consideration and improvements.

  14. Mycobacterium talmoniae sp. nov., a slowly growing mycobacterium isolated from human respiratory samples. (United States)

    Davidson, Rebecca M; DeGroote, Mary Ann; Marola, Jamie L; Buss, Sarah; Jones, Victoria; McNeil, Michael R; Freifeld, Alison G; Elaine Epperson, L; Hasan, Nabeeh A; Jackson, Mary; Iwen, Peter C; Salfinger, Max; Strong, Michael


    A novel slowly growing, non-chromogenic species of the class Actinobacteria was isolated from a human respiratory sample in Nebraska, USA, in 2012. Analysis of the internal transcribed spacer sequence supported placement into the genus Mycobacterium with high sequence similarity to a previously undescribed strain isolated from a patient respiratory sample from Oregon, USA, held in a collection in Colorado, USA, in 2000. The two isolates were subjected to phenotypic testing and whole genome sequencing and found to be indistinguishable. The bacteria were acid-fast stain-positive, rod-shaped and exhibited growth after 7-10 days on solid media at temperatures ranging from 25 to 42°C. Colonies were non-pigmented, rough and slightly raised. Analyses of matrix-assisted laser desorption ionization time-of-flight profiles showed no matches against a reference library of 130 mycobacterial species. Full-length 16S rRNA gene sequences were identical for the two isolates, the average nucleotide identity (ANI) between their genomes was 99.7 % and phylogenetic comparisons classified the novel mycobacteria as the basal most species in the slowly growing Mycobacterium clade. Mycobacterium avium is the most closely related species based on rpoB gene sequence similarity (92 %), but the ANI between the genomes was 81.5 %, below the suggested cut-off for differentiating two species (95 %). Mycolic acid profiles were more similar to M. avium than to Mycobacterium simiae or Mycobacterium abscessus. The phenotypic and genomic data support the conclusion that the two related isolates represent a novel Mycobacterium species for which the name Mycobacterium talmoniae sp. nov. is proposed. The type strain is NE-TNMC-100812T (=ATCC BAA-2683T=DSM 46873T).

  15. Human adenylate kinases – classification, structure, physiological and pathological importance

    Directory of Open Access Journals (Sweden)

    Magdalena Wujak


    Full Text Available Adenylate kinase (AK, EC is a ubiquitous phosphotransferase which catalyzes the reversible transfer of high-energy β – and γ-phosphate groups between nucleotides. All classified AKs show a similar structure: they contain a large central CORE region, nucleoside monophosphate and triphosphate binding domains (NMPbd and NTPbd and the LID domain. Analysis of amino acid sequence similarity revealed the presence of as many as nine human AK isoenzymes, which demonstrate different organ-tissue and intercellular localization. Among these kinases, only two, AK1 and AK2, fulfill the structural and functional criterion by the highest affinity for adenine nucleotides and the utilization of only AMP or dAMP as phosphate acceptors. Human AK isoenzymes are involved in nucleotide homeostasis and monitor disturbances of cell energy charge. Participating in large regulatory protein complexes, AK supplies high energy substrates for controlling the functions of channels and transporters as well as ligands for extracellular P2 nucleotide receptors. In pathological conditions AK can take over the function of other kinases, such as creatine kinase in oxygen-depleted myocardium. Directed mutagenesis and genetic studies of diseases (such as aleukocytosis, hemolytic anemia, primary ciliary dyskinesia (PCD link the presence and activity of AK with etiology of these disturbances. Moreover, AK participates in regulation of differentiation and maturation of cells as well as in apoptosis and oncogenesis. Involvement of AK in a wide range of processes and the correlation between AK and etiology of diseases support the medical potential for the use of adenylate kinases in the diagnosis and treatment of certain diseases. This paper summarizes the current knowledge on the structure, properties and functions of human adenylate kinase.

  16. Transplantation of specific human astrocytes promotes functional recovery after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Stephen J A Davies


    Full Text Available Repairing trauma to the central nervous system by replacement of glial support cells is an increasingly attractive therapeutic strategy. We have focused on the less-studied replacement of astrocytes, the major support cell in the central nervous system, by generating astrocytes from embryonic human glial precursor cells using two different astrocyte differentiation inducing factors. The resulting astrocytes differed in expression of multiple proteins thought to either promote or inhibit central nervous system homeostasis and regeneration. When transplanted into acute transection injuries of the adult rat spinal cord, astrocytes generated by exposing human glial precursor cells to bone morphogenetic protein promoted significant recovery of volitional foot placement, axonal growth and notably robust increases in neuronal survival in multiple spinal cord laminae. In marked contrast, human glial precursor cells and astrocytes generated from these cells by exposure to ciliary neurotrophic factor both failed to promote significant behavioral recovery or similarly robust neuronal survival and support of axon growth at sites of injury. Our studies thus demonstrate functional differences between human astrocyte populations and suggest that pre-differentiation of precursor cells into a specific astrocyte subtype is required to optimize astrocyte replacement therapies. To our knowledge, this study is the first to show functional differences in ability to promote repair of the injured adult central nervous system between two distinct subtypes of human astrocytes derived from a common fetal glial precursor population. These findings are consistent with our previous studies of transplanting specific subtypes of rodent glial precursor derived astrocytes into sites of spinal cord injury, and indicate a remarkable conservation from rat to human of functional differences between astrocyte subtypes. In addition, our studies provide a specific population of human

  17. Primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 encodes a novel Rac1/Cdc42 GAP that modulates cell migration and blood-aqueous barrier function. (United States)

    Lee, Mei-Chin; Shei, William; Chan, Anita S; Chua, Boon-Tin; Goh, Shuang-Ru; Chong, Yaan-Fun; Hilmy, Maryam H; Nongpiur, Monisha E; Baskaran, Mani; Khor, Chiea-Chuen; Aung, Tin; Hunziker, Walter; Vithana, Eranga N


    PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG), encodes an apical junctional protein expressed in components of the blood aqueous barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells and in iris tissue of PACG patients. PLEKHA7 expression also correlated with the C risk allele of the sentinel SNP rs11024102 with the risk allele carrier groups having significantly reduced PLEKHA7 levels compared to non-risk allele carriers. Silencing of PLEKHA7 in human immortalized non-pigmented ciliary epithelium (h-iNPCE) and primary trabecular meshwork cells, which are intimately linked to BAB and aqueous humor outflow respectively, affected actin cytoskeleton organization. PLEKHA7 specifically interacts with GTP-bound Rac1 and Cdc42, but not RhoA, and the activation status of the two small GTPases is linked to PLEKHA7 expression levels. PLEKHA7 stimulates Rac1 and Cdc42 GTP hydrolysis, without affecting nucleotide exchange, identifying PLEKHA7 as a novel Rac1/Cdc42 GAP. Consistent with the regulatory role of Rac1 and Cdc42 in maintaining the tight junction permeability, silencing of PLEKHA7 compromises the paracellular barrier between h-iNPCE cells. Thus, downregulation of PLEKHA7 in PACG may affect BAB integrity and aqueous humor outflow via its Rac1/Cdc42 GAP activity, thereby contributing to disease etiology. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email:

  18. Hyperspectral Imaging Using Intracellular Spies: Quantitative Real-Time Measurement of Intracellular Parameters In Vivo during Interaction of the Pathogenic Fungus Aspergillus fumigatus with Human Monocytes.

    Directory of Open Access Journals (Sweden)

    Sara Mohebbi

    Full Text Available Hyperspectral imaging (HSI is a technique based on the combination of classical spectroscopy and conventional digital image processing. It is also well suited for the biological assays and quantitative real-time analysis since it provides spectral and spatial data of samples. The method grants detailed information about a sample by recording the entire spectrum in each pixel of the whole image. We applied HSI to quantify the constituent pH variation in a single infected apoptotic monocyte as a model system. Previously, we showed that the human-pathogenic fungus Aspergillus fumigatus conidia interfere with the acidification of phagolysosomes. Here, we extended this finding to monocytes and gained a more detailed analysis of this process. Our data indicate that melanised A. fumigatus conidia have the ability to interfere with apoptosis in human monocytes as they enable the apoptotic cell to recover from mitochondrial acidification and to continue with the cell cycle. We also showed that this ability of A. fumigatus is dependent on the presence of melanin, since a non-pigmented mutant did not stop the progression of apoptosis and consequently, the cell did not recover from the acidic pH. By conducting the current research based on the HSI, we could measure the intracellular pH in an apoptotic infected human monocyte and show the pattern of pH variation during 35 h of measurements. As a conclusion, we showed the importance of melanin for determining the fate of intracellular pH in a single apoptotic cell.

  19. Human engineering

    International Nuclear Information System (INIS)

    Yang, Seong Hwan; Park, Bum; Gang, Yeong Sik; Gal, Won Mo; Baek, Seung Ryeol; Choe, Jeong Hwa; Kim, Dae Sung


    This book mentions human engineering, which deals with introduction of human engineering, Man-Machine system like system design, and analysis and evaluation of Man-Machine system, data processing and data input, display, system control of man, human mistake and reliability, human measurement and design of working place, human working, hand tool and manual material handling, condition of working circumstance, working management, working analysis, motion analysis working measurement, and working improvement and design in human engineering.

  20. Human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de


    Human rights reflect a determined effort to protect the dignity of each and every human being against abuse of power. This endeavour is as old as human history. What is relatively new is the international venture for the protection of human dignity through internationally accepted legal standards

  1. Human reliability

    International Nuclear Information System (INIS)

    Embrey, D.E.


    Concepts and techniques of human reliability have been developed and are used mostly in probabilistic risk assessment. For this, the major application of human reliability assessment has been to identify the human errors which have a significant effect on the overall safety of the system and to quantify the probability of their occurrence. Some of the major issues within human reliability studies are reviewed and it is shown how these are applied to the assessment of human failures in systems. This is done under the following headings; models of human performance used in human reliability assessment, the nature of human error, classification of errors in man-machine systems, practical aspects, human reliability modelling in complex situations, quantification and examination of human reliability, judgement based approaches, holistic techniques and decision analytic approaches. (UK)

  2. Human Rights, Human Needs, Human Development, Human Security


    Gasper, Des


    Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each has emerged within the United Nations world; each relies implicitly on a conceptualisation of human need; each has specific strengths. Yet mutual communication, understanding and co-operation are deficient, espec...

  3. Human niche, human behaviour, human nature. (United States)

    Fuentes, Agustin


    The concept of a 'human nature' or 'human natures' retains a central role in theorizing about the human experience. In Homo sapiens it is clear that we have a suite of capacities generated via our evolutionary past, and present, and a flexible capacity to create and sustain particular kinds of cultures and to be shaped by them. Regardless of whether we label these capacities 'human natures' or not, humans occupy a distinctive niche and an evolutionary approach to examining it is critical. At present we are faced with a few different narratives as to exactly what such an evolutionary approach entails. There is a need for a robust and dynamic theoretical toolkit in order to develop a richer, and more nuanced, understanding of the cognitively sophisticated genus Homo and the diverse sorts of niches humans constructed and occupied across the Pleistocene, Holocene, and into the Anthropocene. Here I review current evolutionary approaches to 'human nature', arguing that we benefit from re-framing our investigations via the concept of the human niche and in the context of the extended evolutionary synthesis (EES). While not a replacement of standard evolutionary approaches, this is an expansion and enhancement of our toolkit. I offer brief examples from human evolution in support of these assertions.

  4. Biomicroscopia ultra-sônica (UBM no planejamento cirúrgico e acompanhamento pós-operatório de melanomas malignos de íris e corpo ciliar Ultrasound biomicroscopy (UBM in the surgical planning and postoperative follow-up of iris and ciliary body melanomas

    Directory of Open Access Journals (Sweden)

    Zélia Maria da Silva Corrêa


    Full Text Available OBJETIVO: Estudar os achados da biomicroscopia ultra-sônica (UBM em melanomas malignos primários da íris e corpo ciliar antes e depois da resecção cirúrgica e correlacionar a extensão do tumor (revelado pela biomicroscopia ultra-sônica aos achados histopatológicos. MÉTODOS: Estudo prospectivo de 5 pacientes com diagnóstico clínico de tumor de íris e/ou corpo ciliar. Estes pacientes foram avaliados pela biomicroscopia ultra-sônica antes e após iridociclectomia ou iridectomia. Os espécimens foram enviados para estudo histopatológico. Os pacientes foram acompanhados por período mínimo de 6 meses quando foi realizada nova biomicroscopia ultra-sônica. RESULTADOS: Neste grupo de 5 pacientes, 3 eram do sexo feminino e 2, do masculino, variação de idade de 32 e 64 anos. Todos os casos eram unilaterais. Quatro pacientes apresentaram massa iridociliar e um apresentou lesão limitada à íris. Em todos os casos a biomicroscopia ultra-sônica auxiliou o planejamento cirúrgico para a ressecção tumoral com margens livres. A biomicroscopia ultra-sônica no pós-operatório revelou ausência de crescimento tumoral em todos os casos, sendo que 2 pacientes apresentaram vítreo na incisão cirúrgica, 1 deles com tração vítrea leve, mas sem sinais de descolamento de retina. CONCLUSÃO: A biomicroscopia ultra-sônica pareceu ser método auxiliar confiável para diagnosticar tumores de íris e corpo ciliar, planejar o tratamento cirúrgico e o acompanhamento pós-operatório.PURPOSE: To study pre-operatively and post-operatively ultrasound biomicroscopy (UBM findings of iris and ciliary body melanomas and correlate tumor extension (revealed by ultrasound biomicroscopy with histopathology findings. METHODS: Prospective study of 5 patients with a clinical diagnosis of iris and ciliary body tumors. These patients were evaluated by ultrasound biomicroscopy before and after treatment with iridectomy or iridociclectomy. All specimens were sent

  5. Human Smuggling

    NARCIS (Netherlands)

    Siegel - Rozenblit, Dina; Zaitch, Damian


    Human smuggling is based on a consensus between smuggler, smuggled, and his/her family (which usually guarantees or effectuates payment). However, unauthorized immigrants are violating immigration laws and human smugglers are profiting from enabling illegal immigration. Both human smuggling and its

  6. Human intrusion

    International Nuclear Information System (INIS)

    Hora, S.; Neill, R.; Williams, R.; Bauser, M.; Channell, J.


    This paper focused on the possible approaches to evaluating the impacts of human intrusion on nuclear waste disposal. Several major issues were reviewed. First, it was noted that human intrusion could be addressed either quantitatively through performance assessments or qualitatively through design requirements. Second, it was decided that it was impossible to construct a complete set of possible future human intrusion scenarios. Third, the question of when the effect of possible human intrusion should be considered, before or after site selection was reviewed. Finally, the time frame over which human intrusion should be considered was discussed

  7. Human Technology and Human Affects

    DEFF Research Database (Denmark)

    Fausing, Bent


    Human Technology and Human Affects  This year Samsung introduced a mobile phone with "Soul". It was made with a human touch and included itself a magical touch. Which function does technology and affects get in everyday aesthetics like this, its images and interactions included this presentation...... will ask and try to answer. The mobile phone and its devices are depicted as being able to make a unique human presence, interaction, and affect. The medium, the technology is a necessary helper to get towards this very special and lost humanity. Without the technology, no special humanity - soul....... The paper will investigate how technology, humanity, affects, and synaesthesia are presented and combined with examples from everyday aesthetics, e.g. early computer tv-commercial, net-commercial for mobile phones. Technology and affects point, is the conclusion, towards a forgotten pre-human and not he...

  8. Human Parvoviruses (United States)

    Söderlund-Venermo, Maria; Young, Neal S.


    SUMMARY Parvovirus B19 (B19V) and human bocavirus 1 (HBoV1), members of the large Parvoviridae family, are human pathogens responsible for a variety of diseases. For B19V in particular, host features determine disease manifestations. These viruses are prevalent worldwide and are culturable in vitro, and serological and molecular assays are available but require careful interpretation of results. Additional human parvoviruses, including HBoV2 to -4, human parvovirus 4 (PARV4), and human bufavirus (BuV) are also reviewed. The full spectrum of parvovirus disease in humans has yet to be established. Candidate recombinant B19V vaccines have been developed but may not be commercially feasible. We review relevant features of the molecular and cellular biology of these viruses, and the human immune response that they elicit, which have allowed a deep understanding of pathophysiology. PMID:27806994

  9. Ex vivo study of dentate gyrus neurogenesis in human pharmacoresistant temporal lobe epilepsy. (United States)

    Paradisi, M; Fernández, M; Del Vecchio, G; Lizzo, G; Marucci, G; Giulioni, M; Pozzati, E; Antonelli, T; Lanzoni, G; Bagnara, G P; Giardino, L; Calzà, L


    Neurogenesis in adult humans occurs in at least two areas of the brain, the subventricular zone of the telencephalon and the subgranular layer of the dentate gyrus in the hippocampal formation. We studied dentate gyrus subgranular layer neurogenesis in patients subjected to tailored antero-mesial temporal resection including amygdalohippocampectomy due to pharmacoresistant temporal lobe epilepsy (TLE) using the in vitro neurosphere assay. Sixteen patients were enrolled in the study; mesial temporal sclerosis (MTS) was present in eight patients. Neurogenesis was investigated by ex vivo neurosphere expansion in the presence of mitogens (epidermal growth factor + basic fibroblast growth factor) and spontaneous differentiation after mitogen withdrawal. Growth factor synthesis was investigated by qRT-PCR in neurospheres. We demonstrate that in vitro proliferation of cells derived from dentate gyrus of TLE patients is dependent on disease duration. Moreover, the presence of MTS impairs proliferation. As long as in vitro proliferation occurs, neurogenesis is maintained, and cells expressing a mature neurone phenotype (TuJ1, MAP2, GAD) are spontaneously formed after mitogen withdrawal. Finally, formed neurospheres express mRNAs encoding for growth (vascular endothelial growth factor) as well as neurotrophic factors (brain-derived neurotrophic factor, ciliary neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor). We demonstrated that residual neurogenesis in the subgranular layer of the dentate gyrus in TLE is dependent on diseases duration and absent in MTS. © 2010 The Authors. Neuropathology and Applied Neurobiology © 2010 British Neuropathological Society.

  10. In vitro safety evaluation of human nasal epithelial cell monolayers exposed to carrageenan sinus wash. (United States)

    Ramezanpour, Mahnaz; Murphy, Jae; Smith, Jason L P; Vreugde, Sarah; Psaltis, Alkis James


    Carrageenans have shown to reduce the viral load in nasal secretions and lower the incidence of secondary infections in children with common cold. Despite the widespread use of carrageenans in topical applications, the effect of carrageenans on the sinonasal epithelial barrier has not been elucidated. We investigate the effect of different carrageenans on the sinonasal epithelial barrier and inflammatory response in vitro. Iota and Kappa carrageenan delivered in saline irrigation solutions applied to air-liquid interface (ALI) cultures of primary human nasal epithelial cells from chronic rhinosinusitis patients and controls. Epithelial barrier structure was assessed by measuring the transepithelial electrical resistance (TEER) and immunolocalization of F actin. Ciliary beat frequency (CBF), toxicity, and inflammatory response was studied. Kappa or Iota carrageenan in the different solutions was not toxic, did not have detrimental effects on epithelial barrier structure and CBF. Rather, application of Kappa carrageenan significantly increased TEER and suppressed interleukin 6 (IL-6) secretion in ALI cultures from CRS patients. Kappa or Iota carrageenan solution was safe and did not negatively affect epithelial barrier function. Kappa carrageenan increased TEER and decreased IL-6 production in CRS patients, indicating positive effects on epithelial barrier function in vitro. © 2017 ARS-AAOA, LLC.

  11. Human Rights/Human Needs. (United States)

    Canning, Cynthia


    The faculty of Holy Names High School developed an interdisciplinary human rights program with school-wide activities focusing on three selected themes: the United Nations Universal Declaration of Human Rights, in conjunction with Human Rights Week; Food; and Women. This article outlines major program activities. (SJL)

  12. Staged Bilateral Laparoscopic Adrenalectomy for Infantile ACTH-independent Cushing's Syndrome (Bilateral Micronodular Non-pigmented Adrenal Hyperplasia): A Case Report. (United States)

    Simforoosh, Nasser; Razzaghy Azar, Maryam; Soltani, Mohmmad Hossein; Nourbakhsh, Mona; Shemshaki, Hamidreza


    ACTH-independent Cushing's syndrome is an uncommon disorder in children. While laparoscopic adrenalectomy is well-established in adults, it is rarely used in infants and is associated with some concerns. A seven-month infant was referred to our hospital due to progressive signs and symptoms of Cushing's syndrome. Laboratory data confirmed ACTH-independent hypercortisolism. No history of exogenous corticosteroid contact was observed. The patient underwent left transperitoneal laparoscopic adrenalectomy when she was 7 months old, nevertheless,complete response was not seen. The patient underwent right laparoscopic adrenalectomy (contra-lateral adrenal gland) when she was 20 months old. The signs and symptoms of Cushing's syndrome began to resolve and serum and urine cortisol levels became normal 3 months after the second surgery. laparoscopic adrenalectomy is safe and feasible in infants, and in this case, relieved patient of the symptoms and saved her life.

  13. Human Rights, Human Needs, Human Development, Human Security - Relationships between four international human discourses.

    NARCIS (Netherlands)

    D.R. Gasper (Des)


    markdownabstractAbstract: Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and

  14. Human evolution

    DEFF Research Database (Denmark)

    Llamas, Bastien; Willerslev, Eske; Orlando, Ludovic Antoine Alexandre


    The field of human ancient DNA (aDNA) has moved from mitochondrial sequencing that suffered from contamination and provided limited biological insights, to become a fully genomic discipline that is changing our conception of human history. Recent successes include the sequencing of extinct homini...

  15. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard


    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...... with the human-centered theory of communication advocated by integrationism....

  16. Human kapital

    DEFF Research Database (Denmark)

    Grosen, Anders; Nielsen, Peder Harbjerg


    finansiel og human kapital. Den traditionelle rådgivnings snævre synsvinkel kan føre til forkerte investeringsråd. Der skal derfor opfordres til, at de finansielle virksomheder i tilrettelæggelsen af deres rådgivning af private kunder systematisk inddrager den humane kapitals størrelse og karakteristika i...

  17. Human trichuriasis

    DEFF Research Database (Denmark)

    Betson, Martha; Søe, Martin Jensen; Nejsum, Peter


    Human trichuriasis is a neglected tropical disease which affects hundreds of millions of people worldwide and is particularly prevalent among children living in areas where sanitation is poor. This review examines the current knowledge on the taxonomy, genetics and phylogeography of human Trichuris...

  18. Digital Humanities

    DEFF Research Database (Denmark)

    Brügger, Niels


    , and preserving material to study, as an object of study in its own right, as an analytical tool, or for collaborating, and for disseminating results. The term "digital humanities" was coined around 2001, and gained currency within academia in the following years. However, computers had been used within......Digital humanities is an umbrella term for theories, methodologies, and practices related to humanities scholarship that use the digital computer as an integrated and essential part of its research and teaching activities. The computer can be used for establishing, finding, collecting...

  19. Human Computation

    CERN Multimedia

    CERN. Geneva


    What if people could play computer games and accomplish work without even realizing it? What if billions of people collaborated to solve important problems for humanity or generate training data for computers? My work aims at a general paradigm for doing exactly that: utilizing human processing power to solve computational problems in a distributed manner. In particular, I focus on harnessing human time and energy for addressing problems that computers cannot yet solve. Although computers have advanced dramatically in many respects over the last 50 years, they still do not possess the basic conceptual intelligence or perceptual capabilities...

  20. Human expunction (United States)

    Klee, Robert


    Thomas Nagel in `The Absurd' (Nagel 1971) mentions the future expunction of the human species as a `metaphor' for our ability to see our lives from the outside, which he claims is one source of our sense of life's absurdity. I argue that the future expunction (not to be confused with extinction) of everything human - indeed of everything biological in a terran sense - is not a mere metaphor but a physical certainty under the laws of nature. The causal processes by which human expunction will take place are presented in some empirical detail, so that philosophers cannot dismiss it as merely speculative. I also argue that appeals to anthropic principles or to forms of mystical cosmology are of no plausible avail in the face of human expunction under the laws of physics.

  1. Human Cloning

    National Research Council Canada - National Science Library

    Johnson, Judith A; Williams, Erin D


    .... Scientists in other labs, including Harvard University and the University of California at San Francisco, intend to produce cloned human embryos in order to derive stem cells for medical research...

  2. Human brucellosis

    NARCIS (Netherlands)

    Franco, María Pía; Mulder, Maximilian; Gilman, Robert H.; Smits, Henk L.


    Human brucellosis still presents scientists and clinicians with several challenges, such as the understanding of pathogenic mechanisms of Brucella spp, the identification of markers for disease severity, progression, and treatment response, and the development of improved treatment regimens.

  3. Human settlements

    CSIR Research Space (South Africa)

    Van Niekerk, Cornelia W


    Full Text Available risk of deaths and injuries by drowning in floods and migration- related health effects. • Increased migration, which can result in human suffering, human rights violations, conflicts and political instability. • Loss of property and livelihoods.... The vulnerability of settlements in southern Africa is impacted by various and complex socio-economic processes related to the cultural, political and institutional contexts and demographic pressure, as well as specific high-risk zones susceptible to flash floods...

  4. Human Cloning (United States)


    Human Fertilization and Embryology Authority (HFEA). A team of scientists headed by Alison Murdoch at the University of Newcastle received permission...not yet reported success in isolating stem cells from a cloned human embryo. A research team headed by Ian Wilmut at the University of Edinburgh...research group, headed by Douglas Melton and Kevin Eggan, submitted their proposal to a Harvard committee composed of ethicists, scientists and public

  5. Comparative Effects of Human Neural Stem Cells and Oligodendrocyte Progenitor Cells on the Neurobehavioral Disorders of Experimental Autoimmune Encephalomyelitis Mice

    Directory of Open Access Journals (Sweden)

    Dae-Kwon Bae


    Full Text Available Since multiple sclerosis (MS is featured with widespread demyelination caused by autoimmune response, we investigated the recovery effects of F3.olig2 progenitors, established by transducing human neural stem cells (F3 NSCs with Olig2 transcription factor, in myelin oligodendrocyte glycoprotein- (MOG- induced experimental autoimmune encephalomyelitis (EAE model mice. Six days after EAE induction, F3 or F3.olig2 cells (1 × 106/mouse were intravenously transplanted. MOG-injected mice displayed severe neurobehavioral deficits which were remarkably attenuated and restored by cell transplantation, in which F3.olig2 cells were superior to its parental F3 cells. Transplanted cells migrated to the injured spinal cord, matured to oligodendrocytes, and produced myelin basic proteins (MBP. The F3.olig2 cells expressed growth and neurotrophic factors including brain-derived neurotrophic factor (BDNF, nerve growth factor (NGF, ciliary neurotrophic factor (CNTF, and leukemia inhibitory factor (LIF. In addition, the transplanted cells markedly attenuated inflammatory cell infiltration, reduced cytokine levels in the spinal cord and lymph nodes, and protected host myelins. The results indicate that F3.olig2 cells restore neurobehavioral symptoms of EAE mice by regulating autoimmune inflammatory responses as well as by stimulating remyelination and that F3.olig2 progenitors could be a candidate for the cell therapy of demyelinating diseases including MS.

  6. Human cognition

    International Nuclear Information System (INIS)

    Norman, D.A.


    The study of human cognition encompasses the study of all mental phenomena, from the receipt and interpretation of sensory information to the final control of the motor system in the performance of action. The cognitive scientist examines all intermediary processes, including thought, decision making, and memory and including the effects of motivation, states of arousal and stress, the study of language, and the effects of social factors. The field therefore ranges over an enormous territory, covering all that is known or that should be known about human behavior. It is not possible to summarize the current state of knowledge about cognition with any great confidence that we know the correct answer about any aspect of the work. Nontheless, models provide good characterizations of certain aspects of the data and situations. Even if these models should prove to be incorrect, they do provide good approximate descriptions of people's behavior in some situations, and these approximations will still apply even when the underlying theories have changed. A quick description is provided of models within a number of areas of human cognition and skill and some general theoretical frameworks with which to view human cognition. The frameworks are qualitative descriptions that provide a way to view the development of more detailed, quantitative models and, most important, a way of thinking about human performance and skill

  7. Swimming direction reversal of flagella through ciliary motion of mastigonemes

    NARCIS (Netherlands)

    Namdeo, S.; Khaderi, S. N.; den Toonder, J.M.J.; Onck, P. R.; Colin, S.; Morini, G.L.

    Bio-inspired designs can provide an answer to engineering problems such as swimming strategies at the micron or nano-scale. Scientists are now designing artificial micro-swimmers that can mimic flagella-powered swimming of micro-organisms. In an application such as lab-on-a-chip in which

  8. Regulation of the branchial ciliary activity in the mussel

    NARCIS (Netherlands)

    Dral, A.D.G.


    In mussels the movement of the cilia on the gill are basically autonomous and influenced by environmental factors. The branchial nerve has an inhibitory as well as a stimulating effect on the activity of the lateral cilia. The reactions of these cilia to changing temperature and chlorinity in

  9. Artificial cilia : a physical model for ciliary propulsion


    Babataheri , Avin


    Most microorganisms use cilia or flagella as a means of propulsion. These low Reynolds number swimming mechanisms have been studied theoretically and experimentally on living organisms. However, so far very few physical experimental models have been realised. We describe here the fabrication of microscopic artificial cilia, actuated by a magnetic field. These artificial cilia share with real cilia a large aspect ratio, great flexibility, and the actuation by a magnetic torque distributed alon...

  10. Ciliary heterogeneity within a single cell: the Paramecium model. (United States)

    Aubusson-Fleury, Anne; Cohen, Jean; Lemullois, Michel


    Paramecium is a single cell able to divide in its morphologically differentiated stage that has many cilia anchored at its cell surface. Many thousands of cilia are thus assembled in a short period of time during division to duplicate the cell pattern while the cell continues swimming. Most, but not all, of these sensory cilia are motile and involved in two main functions: prey capture and cell locomotion. These cilia display heterogeneity, both in their length and their biochemical properties. Thanks to these properties, as well as to the availability of many postgenomic tools and the possibility to follow the regrowth of cilia after deciliation, Paramecium offers a nice opportunity to study the assembly of the cilia, as well as the genesis of their diversity within a single cell. In this paper, after a brief survey of Paramecium morphology and cilia properties, we describe the tools and the protocols currently used for immunofluorescence, transmission electron microscopy, and ultrastructural immunocytochemistry to analyze cilia, with special recommendations to overcome the problem raised by cilium diversity. Copyright © 2015. Published by Elsevier Inc.

  11. VAMP7 modulates ciliary biogenesis in kidney cells.

    Directory of Open Access Journals (Sweden)

    Christina M Szalinski

    Full Text Available Epithelial cells elaborate specialized domains that have distinct protein and lipid compositions, including the apical and basolateral surfaces and primary cilia. Maintaining the identity of these domains is required for proper cell function, and requires the efficient and selective SNARE-mediated fusion of vesicles containing newly synthesized and recycling proteins with the proper target membrane. Multiple pathways exist to deliver newly synthesized proteins to the apical surface of kidney cells, and the post-Golgi SNAREs, or VAMPs, involved in these distinct pathways have not been identified. VAMP7 has been implicated in apical protein delivery in other cell types, and we hypothesized that this SNARE would have differential effects on the trafficking of apical proteins known to take distinct routes to the apical surface in kidney cells. VAMP7 expressed in polarized Madin Darby canine kidney cells colocalized primarily with LAMP2-positive compartments, and siRNA-mediated knockdown modulated lysosome size, consistent with the known function of VAMP7 in lysosomal delivery. Surprisingly, VAMP7 knockdown had no effect on apical delivery of numerous cargoes tested, but did decrease the length and frequency of primary cilia. Additionally, VAMP7 knockdown disrupted cystogenesis in cells grown in a three-dimensional basement membrane matrix. The effects of VAMP7 depletion on ciliogenesis and cystogenesis are not directly linked to the disruption of lysosomal function, as cilia lengths and cyst morphology were unaffected in an MDCK lysosomal storage disorder model. Together, our data suggest that VAMP7 plays an essential role in ciliogenesis and lumen formation. To our knowledge, this is the first study implicating an R-SNARE in ciliogenesis and cystogenesis.

  12. Ciliary Body Tumour Occurring in a Nigerian - A case report ...

    African Journals Online (AJOL)

    Objective: To report the rare case of a 33-year-old female Nigerian who presented to our retina clinic with a chronic total retinal detachment and visual acuity of no light perception in her left eye. Re-attachment surgery in the eye was not attempted as prognosis for return of vision was poor. She was later noted to harbor a ...

  13. Primary ciliary dyskinesia: Kartagener syndrome in a family with a ...

    African Journals Online (AJOL)

    Makia J. Marafie


    Dec 22, 2014 ... flagella of sperm tail, brain and spinal cord ependyma [2]. Many syndromes are linked to ... VC) to left sided superior caval vein (right sided inferior caval vein), and with S/P left .... east: nature versus nurture. Open Complement ...

  14. Towards Clinical Application of Neurotrophic Factors to the Auditory Nerve; Assessment of Safety and Efficacy by a Systematic Review of Neurotrophic Treatments in Humans

    Directory of Open Access Journals (Sweden)

    Aren Bezdjian


    Full Text Available Animal studies have evidenced protection of the auditory nerve by exogenous neurotrophic factors. In order to assess clinical applicability of neurotrophic treatment of the auditory nerve, the safety and efficacy of neurotrophic therapies in various human disorders were systematically reviewed. Outcomes of our literature search included disorder, neurotrophic factor, administration route, therapeutic outcome, and adverse event. From 2103 articles retrieved, 20 randomized controlled trials including 3974 patients were selected. Amyotrophic lateral sclerosis (53% was the most frequently reported indication for neurotrophic therapy followed by diabetic polyneuropathy (28%. Ciliary neurotrophic factor (50%, nerve growth factor (24% and insulin-like growth factor (21% were most often used. Injection site reaction was a frequently occurring adverse event (61% followed by asthenia (24% and gastrointestinal disturbances (20%. Eighteen out of 20 trials deemed neurotrophic therapy to be safe, and six out of 17 studies concluded the neurotrophic therapy to be effective. Positive outcomes were generally small or contradicted by other studies. Most non-neurodegenerative diseases treated by targeted deliveries of neurotrophic factors were considered safe and effective. Hence, since local delivery to the cochlea is feasible, translation from animal studies to human trials in treating auditory nerve degeneration seems promising.

  15. Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease. (United States)

    Lewis, Wesley R; Malarkey, Erik B; Tritschler, Douglas; Bower, Raqual; Pasek, Raymond C; Porath, Jonathan D; Birket, Susan E; Saunier, Sophie; Antignac, Corinne; Knowles, Michael R; Leigh, Margaret W; Zariwala, Maimoona A; Challa, Anil K; Kesterson, Robert A; Rowe, Steven M; Drummond, Iain A; Parant, John M; Hildebrandt, Friedhelm; Porter, Mary E; Yoder, Bradley K; Berbari, Nicolas F


    Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or 'primary' cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh) signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400). While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8). GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC) protein 4 (DRC4) where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR) to generate one of these human missense variants in

  16. Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease.

    Directory of Open Access Journals (Sweden)

    Wesley R Lewis


    Full Text Available Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or 'primary' cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400. While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8. GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC protein 4 (DRC4 where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR to generate one of these human missense

  17. Beyond Humanisms


    Capurro, Rafael


    In the first part of this paper a short history of Western humanisms (Socrates, Pico della Mirandola, Descartes, Kant) is presented. As far as these humanisms rest on a fixation of the ‘humanum’ they are metaphysical, although they might radically differ from each other. The second part deals with the present debate on trans- and posthumanism in the context of some breath-taking developments in science and technology.Angeletics, a theory of messengers and messages, intends to give an answer t...

  18. Human Parechoviruses

    DEFF Research Database (Denmark)

    Fischer, Thea Kølsen; Harvala, Heli; Midgley, Sofie


    Infections with human parechoviruses (HPeV) are highly prevalent, particularly in neonates, where they may cause substantial morbidity and mortality. The clinical presentation of HPeV infection is often indistinguishable from that of enterovirus (EV) infection and may vary from mild disease...

  19. Practicing Humanities

    DEFF Research Database (Denmark)

    Gimmler, Antje


    and self-reflective democracy. Contemporary humanities have adopted a new orientation towards practices, and it is not clear how this fits with the ideals of ‘Bildung’ and ‘pure science’. A possible theoretical framework for this orientation towards practices could be found in John Dewey’s pragmatic...

  20. Human waste

    NARCIS (Netherlands)

    Amin, Md Nurul; Kroeze, Carolien; Strokal, Maryna


    Many people practice open defecation in south Asia. As a result, lot of human waste containing nutrients such as nitrogen (N) and phosphorus (P) enter rivers. Rivers transport these nutrients to coastal waters, resulting in marine pollution. This source of nutrient pollution is, however, ignored in

  1. Human Trafficking (United States)

    Wilson, David McKay


    The shadowy, criminal nature of human trafficking makes evaluating its nature and scope difficult. The U.S. State Department and anti-trafficking groups estimate that worldwide some 27 million people are caught in a form of forced servitude today. Public awareness of modern-day slavery is gaining momentum thanks to new abolitionist efforts. Among…

  2. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard


    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...

  3. Nothing Human (United States)

    Wharram, C. C.


    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  4. Human Rights and Human Function

    Directory of Open Access Journals (Sweden)

    Mohsen Javadi


    Full Text Available This paper firstly explores some theories of Human Rights justification and then assents to the theory that Human Rights is based on justified moral values. In order to justify moral values, Aristotle’s approach called “Function Argument” is reviewed. Propounding this argument, the writer attempts to show that all analysis of human identity will directly contribute to the man’s view of his rights. Not only Human rights is really determined by human function or human distinguishing characteristic i.e. human identity, but in the world of knowledge the proper method to know human rights is to know human being himself. n cloning violates man’s rights due to two reasons: damage of human identity and violation of the right to be unique. Attempting to clarify the nature of human cloning, this article examines the aspects to be claimed to violate human rights and evaluates the strength of the reasons for this claim. این مقاله پس از بررسی اجمالی برخی از نظریه‌های توجیه حقوق بشر، نظریة ابتنای آن بر ارزش‌های اخلاقی موجّه را می‌پذیرد. دربارة چگونگی توجیه ارزش اخلاقی، رویکرد ارسطو که به «برهان ارگن» موسوم است، مورد بحث و بررسی قرار می‌گیرد. مؤلف با طرح این برهان می‌کوشد نشان دهد ارائه هرگونه تحلیل از هویت انسان در نگرش آدمی به حقوق خود تأثیر مستقیم خواهد گذاشت. حقوق آدمی نه فقط از ناحیة کارویژه یا فصل ممیز وی (هویت انسان تعیّن واقعی می‌گیرد، بلکه در عالم معرفت هم راه درست شناخت حقوق بشر، شناخت خود انسان است.

  5. Human Rights, Human Needs, Human Development, Human Security : Relationships between four international 'human' discourses

    NARCIS (Netherlands)

    D.R. Gasper (Des)


    textabstractHuman rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each

  6. Human Face as human single identity


    Warnars, Spits


    Human face as a physical human recognition can be used as a unique identity for computer to recognize human by transforming human face with face algorithm as simple text number which can be primary key for human. Human face as single identity for human will be done by making a huge and large world centre human face database, where the human face around the world will be recorded from time to time and from generation to generation. Architecture database will be divided become human face image ...

  7. Human Rights in the Humanities (United States)

    Harpham, Geoffrey


    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  8. Human reliability

    International Nuclear Information System (INIS)

    Bubb, H.


    This book resulted from the activity of Task Force 4.2 - 'Human Reliability'. This group was established on February 27th, 1986, at the plenary meeting of the Technical Reliability Committee of VDI, within the framework of the joint committee of VDI on industrial systems technology - GIS. It is composed of representatives of industry, representatives of research institutes, of technical control boards and universities, whose job it is to study how man fits into the technical side of the world of work and to optimize this interaction. In a total of 17 sessions, information from the part of ergonomy dealing with human reliability in using technical systems at work was exchanged, and different methods for its evaluation were examined and analyzed. The outcome of this work was systematized and compiled in this book. (orig.) [de

  9. Human paleoneurology

    CERN Document Server


    The book presents an integrative review of paleoneurology, the study of endocranial morphology in fossil species. The main focus is on showing how computed methods can be used to support advances in evolutionary neuroanatomy, paleoanthropology and archaeology and how they have contributed to creating a completely new perspective in cognitive neuroscience. Moreover, thanks to its multidisciplinary approach, the book addresses students and researchers approaching human paleoneurology from different angles and for different purposes, such as biologists, physicians, anthropologists, archaeologists

  10. Human universe

    CERN Document Server

    Cox, Brian


    Human life is a staggeringly strange thing. On the surface of a ball of rock falling around a nuclear fireball in the blackness of a vacuum the laws of nature conspired to create a naked ape that can look up at the stars and wonder where it came from. What is a human being? Objectively, nothing of consequence. Particles of dust in an infinite arena, present for an instant in eternity. Clumps of atoms in a universe with more galaxies than people. And yet a human being is necessary for the question itself to exist, and the presence of a question in the universe - any question - is the most wonderful thing. Questions require minds, and minds bring meaning. What is meaning? I don't know, except that the universe and every pointless speck inside it means something to me. I am astonished by the existence of a single atom, and find my civilisation to be an outrageous imprint on reality. I don't understand it. Nobody does, but it makes me smile. This book asks questions about our origins, our destiny, and our place i...

  11. Myo/Nog cells: targets for preventing the accumulation of skeletal muscle-like cells in the human lens.

    Directory of Open Access Journals (Sweden)

    Jacquelyn Gerhart

    Full Text Available Posterior capsule opacification (PCO is a vision impairing condition that arises in some patients following cataract surgery. The fibrotic form of PCO is caused by myofibroblasts that may emerge in the lens years after surgery. In the chick embryo lens, myofibroblasts are derived from Myo/Nog cells that are identified by their expression of the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein inhibitor Noggin, and the epitope recognized by the G8 monoclonal antibody. The goal of this study was to test the hypothesis that depletion of Myo/Nog cells will prevent the accumulation of myofibroblasts in human lens tissue. Myo/Nog cells were present in anterior, equatorial and bow regions of the human lens, cornea and ciliary processes. In anterior lens tissue removed by capsulorhexis, Myo/Nog cells had synthesized myofibroblast and skeletal muscle proteins, including vimentin, MyoD and sarcomeric myosin. Alpha smooth muscle actin (α-SMA was detected in a subpopulation of Myo/Nog cells. Areas of the capsule denuded of epithelial cells were surrounded by Myo/Nog cells. Some of these cell free areas contained a wrinkle in the capsule. Depletion of Myo/Nog cells eliminated cells expressing skeletal muscle proteins in 5-day cultures but did not affect cells immunoreactive for beaded filament proteins that accumulate in differentiating lens epithelial cells. Transforming growth factor-betas 1 and 2 that mediate an epithelial-mesenchymal transition, did not induce the expression of skeletal muscle proteins in lens cells following Myo/Nog cell depletion. This study demonstrates that Myo/Nog cells in anterior lens tissue removed from cataract patients have undergone a partial differentiation to skeletal muscle. Myo/Nog cells appear to be the source of skeletal muscle-like cells in explants of human lens tissue. Targeting Myo/Nog cells with the G8 antibody during cataract surgery may reduce the incidence of PCO.

  12. A Comprehensive Proteomics Analysis of the Human Iris Tissue: Ready to Embrace Postgenomics Precision Medicine in Ophthalmology? (United States)

    Murthy, Krishna R; Dammalli, Manjunath; Pinto, Sneha M; Murthy, Kalpana Babu; Nirujogi, Raja Sekhar; Madugundu, Anil K; Dey, Gourav; Subbannayya, Yashwanth; Mishra, Uttam Kumar; Nair, Bipin; Gowda, Harsha; Prasad, T S Keshava


    The annual economic burden of visual disorders in the United States was estimated at $139 billion. Ophthalmology is therefore one of the salient application fields of postgenomics biotechnologies such as proteomics in the pursuit of global precision medicine. Interestingly, the protein composition of the human iris tissue still remains largely unexplored. In this context, the uveal tract constitutes the vascular middle coat of the eye and is formed by the choroid, ciliary body, and iris. The iris forms the anterior most part of the uvea. It is a thin muscular diaphragm with a central perforation called pupil. Inflammation of the uvea is termed uveitis and causes reduced vision or blindness. However, the pathogenesis of the spectrum of diseases causing uveitis is still not very well understood. We investigated the proteome of the iris tissue harvested from healthy donor eyes that were enucleated within 6 h of death using high-resolution Fourier transform mass spectrometry. A total of 4959 nonredundant proteins were identified in the human iris, which included proteins involved in signaling, cell communication, metabolism, immune response, and transport. This study is the first attempt to comprehensively profile the global proteome of the human iris tissue and, thus, offers the potential to facilitate biomedical research into pathological diseases of the uvea such as Behcet's disease, Vogt Koyonagi Harada's disease, and juvenile rheumatoid arthritis. Finally, we make a call to the broader visual health and ophthalmology community that proteomics offers a veritable prospect to obtain a systems scale, functional, and dynamic picture of the eye tissue in health and disease. This knowledge is ultimately pertinent for precision medicine diagnostics and therapeutics innovation to address the pressing needs of the 21st century visual health.

  13. Introduction: Digital Humanities, Public Humanities

    Directory of Open Access Journals (Sweden)

    Alex Christie


    Full Text Available NANO: New American Notes Online: An Interdisciplinary Academic Journal for Big Ideas in a Small World. This special issue shows how both public and digital humanities research can be rendered more persuasive through engagement with cultures beyond the academy. More specifically, the aim of this special issue is to demonstrate how investments in technologies and computation are not necessarily antithetical to investments in critical theory and social justice.

  14. Human Capital, (Human) Capabilities and Higher Education (United States)

    Le Grange, L.


    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  15. Extracellular vesicles have variable dose-dependent effects on cultured draining cells in the eye. (United States)

    Tabak, Saray; Schreiber-Avissar, Sofia; Beit-Yannai, Elie


    The role of extracellular vesicles (EVs) as signal mediators has been described in many biological fields. How many EVs are needed to deliver the desired physiological signal is yet unclear. Using a normal trabecular meshwork (NTM) cell culture exposed to non-pigmented ciliary epithelium (NPCE)-derived EVs, a relevant model for studying the human ocular drainage system, we addressed the EVs dose-response effects on the Wnt signaling. The objective of the study was to investigate the dosing effects of NPCE-derived EVs on TM Wnt signaling. EVs were isolated by PEG 8000 method from NPCE and RPE cells (used as controls) conditioned media. Concentrations were determined by Tunable Resistive Pulse Sensing method. Various exosomes concentration were incubated with TM cells, for the determination of mRNA (β-Catenin, Axin2 and LEF1) and protein (β-Catenin, GSK-3β) expression using real-time quantitative PCR and Western blot, respectively. Exposure of NTM cells for 8 hrs to low EVs concentrations was associated with a significant decreased expression of β-Catenin, GSK-3β, as opposed to exposure to high exosomal concentrations. Pro-MMP9 and MMP9 activities were significantly enhanced in NTM cells treated with high EV concentrations of (X10) as compared to low EV concentrations of either NPCE- or RPE-derived EVs and to untreated control. Our data support the concept that EVs biological effects are concentration-dependent at their target site. Specifically in the present study, we described a general dose-response at the gene and MMPs activity and a different dose-response regarding key canonical Wnt proteins expression. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  16. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard


    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  17. Application of neutron activation analysis to biological materials. Pt. 4. Approach to simultaneous determination of trace elements in human eye tissues with non-destructive neutron activation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, T; Bando, M; Nakajima, A [Juntendo Univ., Tokyo (Japan). School of Medicine; Terai, M [Tokyo Metropolitan Univ. (Japan). Faculty of Science; Suzuki-Yasumoto, M [National Inst. of Radiological Sciences, Chiba (Japan)


    Fourteen trace elements (short-lived nuclides: Al, Br, Cu, Mn and V; long-lived nuclides: Ag, Au, Cd, Co, Cr, Fe, Sc, Se and Zn) in human eye tissues are determined simultaneously by non-destructive neutron activation analysis. The quantity of Al, Br, Fe, Se and Zn in the eye tissues (about 1 to more than 10 dry weight tissue) seems to be higher than that of other trace elements, although the content of each trace element in individual tissue is scattered in a wide range. Conjunctiva, iris (+ciliary body) and choroid (+pigment epithelium) seem to contain larger amount of various trace elements than other eye tissues. From correlation studies it is evident that the relative distribution of 14 trace elements in various eye tissues are similar, and furthermore the content of trace elements in the eye tissues may be correlated in each of the three groups (group A: Cd, Se and Zn; group B: Al, Cr, Fe, Se and V; group C: Al, Au, Fe and Se).

  18. Humanized mouse models: Application to human diseases. (United States)

    Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru


    Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

  19. Human steroidogenesis

    DEFF Research Database (Denmark)

    Andersen, Claus Y; Ezcurra, Diego


    In the menstrual cycle, the mid-cycle surge of gonadotropins (both luteinising hormone [LH] and follicle-stimulating hormone [FSH]) signals the initiation of the periovulatory interval, during which the follicle augments progesterone production and begins to luteinise, ultimately leading to the r......In the menstrual cycle, the mid-cycle surge of gonadotropins (both luteinising hormone [LH] and follicle-stimulating hormone [FSH]) signals the initiation of the periovulatory interval, during which the follicle augments progesterone production and begins to luteinise, ultimately leading...... reviews current knowledge of the regulation of progesterone in the human ovary during the follicular phase and highlights areas where knowledge remains limited. In this review, we provide in-depth information outlining the regulation and function of gonadotropins in the complicated area of steroidogenesis...

  20. NATO Human View Architecture and Human Networks (United States)

    Handley, Holly A. H.; Houston, Nancy P.


    The NATO Human View is a system architectural viewpoint that focuses on the human as part of a system. Its purpose is to capture the human requirements and to inform on how the human impacts the system design. The viewpoint contains seven static models that include different aspects of the human element, such as roles, tasks, constraints, training and metrics. It also includes a Human Dynamics component to perform simulations of the human system under design. One of the static models, termed Human Networks, focuses on the human-to-human communication patterns that occur as a result of ad hoc or deliberate team formation, especially teams distributed across space and time. Parameters of human teams that effect system performance can be captured in this model. Human centered aspects of networks, such as differences in operational tempo (sense of urgency), priorities (common goal), and team history (knowledge of the other team members), can be incorporated. The information captured in the Human Network static model can then be included in the Human Dynamics component so that the impact of distributed teams is represented in the simulation. As the NATO militaries transform to a more networked force, the Human View architecture is an important tool that can be used to make recommendations on the proper mix of technological innovations and human interactions.

  1. The Digital Humanities as a Humanities Project (United States)

    Svensson, Patrik


    This article argues that the digital humanities can be seen as a humanities project in a time of significant change in the academy. The background is a number of scholarly, educational and technical challenges, the multiple epistemic traditions linked to the digital humanities, the potential reach of the field across and outside the humanities,…

  2. Managing the Human in Human Brands

    Directory of Open Access Journals (Sweden)

    Fournier Susan


    Full Text Available The physical and social realities, mental biases and limitations of being human differentiate human brands from others. It is their very humanness that introduces risk while generating the ability for enhanced returns. Four particular human characteristics can create imbalance or inconsistency between the person and the brand: mortality, hubris, unpredictability and social embeddedness. None of these qualities manifest in traditional non-human brands, and all of them present risks requiring active managerial attention. Rather than treating humans as brands and making humans into brands for sale in the commercial marketplace, our framework forces a focus on keeping a balance between the person and the personified object.

  3. Human cloning and human dignity

    Directory of Open Access Journals (Sweden)

    Hasan Eslami


    Full Text Available Catholic Church and most of Muslims believe that human cloning is in contrast with human rights. They argue that applying Somatic Nuclear Transfer Technique or so-called cloning to humans is against human dignity. Their main reason is that the cloned person would be a copy or shadow of another person and lack his or her identity and uniqueness. They also argue that in the process of cloning human beings would be treated as laboratory mice. This article tries to evaluate this kind of argumentation and shows that the "human dignity" expression in the relevant writings is vague and has been used inappropriately. مسیحیان و برخی از مسلمانان استدلال می‌کنند که کاربست تکنیک شبیه‌سازی ناقض کرامت انسانی است. این دلیل خود به صورت‌های مختلفی بیان می‌شود، مانند آنکه انسان موضوع آزمایش‌های علمی قرار می‌گیرد و با او مانند حیوانات رفتار می‌شود. گاه نیز تغییر نحوة تولید مثل، مایة نقض کرامت انسانی قلمداد می‌گردد و گاه به مسئلة از بین رفتن هویت فردی اشاره می‌شود. نگارنده در دو قسمت، دیدگاه مسیحیان و مسلمانان را در این باره نقل و تحلیل کرده است و کوشیده است نشان دهد که استناد به مفهوم کرامت انسانی در این جا مبهم و ناگویاست و مخالفان کوشش دقیقی در جهت تبیین دلیل خود به عمل نیاورده‌اند.

  4. Digital Humanities

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørn


    overgangen fra trykkekultur til digital kultur. For det første problemstillingen omkring digitalisering af litterær kulturarv med fokus på kodning og tagging af teksten samt organisering i hypertekststrukturer. For det andet reorganiseringen af det digitale dokument i dataelementer og database. For det......Artiklen præsenterer først nogle generelle problemstillinger omkring Digital Humanities (DH) med det formål at undersøge dem nærmere i relation til konkrete eksempler på forskellige digitaliseringsmåder og ændringer i dokumentproduktion. I en nærmere afgrænsning vælger artiklen den tendens i DH......, der betragter DH som forbundet med "making" og "building" af digitale objekter og former. Dette kan også karakteriseres som DH som praktisk-produktiv vending. Artiklen har valgt tre typer af digitalisering. De er valgt ud fra, at de skal repræsentere forskellige måder at håndtere digitaliseringen på...

  5. Modern Human Engineering

    International Nuclear Information System (INIS)

    Jeong, Byeong Yong; Lee Dong Kyeong


    These are the titles of each chapter. They are as in the following; design of human-centerdness, human machine system, information processing process, sense of human, user interface, elements of human body, vital dynamics, measurement of reaction of human body, estimation and management of working environment, mental characteristic of human, human error, group, organization and leadership, safety supervision, process analysis, time studying, work sampling, work factor and methods time measurement, introduction of muscular skeletal disease and program of preventive management.

  6. Modern Human Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Byeong Yong; Lee Dong Kyeong


    These are the titles of each chapter. They are as in the following; design of human-centerdness, human machine system, information processing process, sense of human, user interface, elements of human body, vital dynamics, measurement of reaction of human body, estimation and management of working environment, mental characteristic of human, human error, group, organization and leadership, safety supervision, process analysis, time studying, work sampling, work factor and methods time measurement, introduction of muscular skeletal disease and program of preventive management.


    Directory of Open Access Journals (Sweden)

    N. S. Shilovskaya


    Full Text Available Article is devoted to the distinction of humanism and anthropocentrism which is based on the parity of the person and being. Genetic communication of humanism and anthropocentrism and their historical break comes to light.

  8. Superintelligence, Humans, and War (United States)


    Recent studies of the human mind debunk the myth that humans only use 10-20 percent of the human mind. A healthy human mind uses up to 90 percent...way. They will eat what is in front of them to satiate their appetite not knowing if there is anymore food for the future. Humans can predict

  9. The golden triangle of human dignity: human security, human development and human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de


    The success or failure of processes of democratization cannot be detached from processes of development related to the aspirations of people at the grassroots. Human rights, in a more theoretical terminology, require human development in order to enhance human security.

  10. Improved neurological outcome by intramuscular injection of human amniotic fluid derived stem cells in a muscle denervation model.

    Directory of Open Access Journals (Sweden)

    Chun-Jung Chen

    Full Text Available The skeletal muscle develops various degrees of atrophy and metabolic dysfunction following nerve injury. Neurotrophic factors are essential for muscle regeneration. Human amniotic fluid derived stem cells (AFS have the potential to secrete various neurotrophic factors necessary for nerve regeneration. In the present study, we assess the outcome of neurological function by intramuscular injection of AFS in a muscle denervation and nerve anastomosis model.Seventy two Sprague-Dawley rats weighing 200-250 gm were enrolled in this study. Muscle denervation model was conducted by transverse resection of a sciatic nerve with the proximal end sutured into the gluteal muscle. The nerve anastomosis model was performed by transverse resection of the sciatic nerve followed by four stitches reconnection. These animals were allocated to three groups: control, electrical muscle stimulation, and AFS groups.NT-3 (Neurotrophin 3, BDNF (Brain derived neurotrophic factor, CNTF (Ciliary neurotrophic factor, and GDNF (Glia cell line derived neurotrophic factor were highly expressed in AFS cells and supernatant of culture medium. Intra-muscular injection of AFS exerted significant expression of several neurotrophic factors over the distal end of nerve and denervated muscle. AFS caused high expression of Bcl-2 in denervated muscle with a reciprocal decrease of Bad and Bax. AFS preserved the muscle morphology with high expression of desmin and acetylcholine receptors. Up to two months, AFS produced significant improvement in electrophysiological study and neurological functions such as SFI (sciatic nerve function index and Catwalk gait analysis. There was also significant preservation of the number of anterior horn cells and increased nerve myelination as well as muscle morphology.Intramuscular injection of AFS can protect muscle apoptosis and likely does so through the secretion of various neurotrophic factors. This protection furthermore improves the nerve

  11. Engrafted human induced pluripotent stem cell-derived anterior specified neural progenitors protect the rat crushed optic nerve.

    Directory of Open Access Journals (Sweden)

    Leila Satarian

    Full Text Available BACKGROUND: Degeneration of retinal ganglion cells (RGCs is a common occurrence in several eye diseases. This study examined the functional improvement and protection of host RGCs in addition to the survival, integration and neuronal differentiation capabilities of anterior specified neural progenitors (NPs following intravitreal transplantation. METHODOLOGY/PRINCIPAL FINDINGS: NPs were produced under defined conditions from human induced pluripotent stem cells (hiPSCs and transplanted into rats whose optic nerves have been crushed (ONC. hiPSCs were induced to differentiate into anterior specified NPs by the use of Noggin and retinoic acid. The hiPSC-NPs were labeled by green fluorescent protein or a fluorescent tracer 1,1' -dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI and injected two days after induction of ONC in hooded rats. Functional analysis according to visual evoked potential recordings showed significant amplitude recovery in animals transplanted with hiPSC-NPs. Retrograde labeling by an intra-collicular DiI injection showed significantly higher numbers of RGCs and spared axons in ONC rats treated with hiPSC-NPs or their conditioned medium (CM. The analysis of CM of hiPSC-NPs showed the secretion of ciliary neurotrophic factor, basic fibroblast growth factor, and insulin-like growth factor. Optic nerve of cell transplanted groups also had increased GAP43 immunoreactivity and myelin staining by FluoroMyelin™ which imply for protection of axons and myelin. At 60 days post-transplantation hiPSC-NPs were integrated into the ganglion cell layer of the retina and expressed neuronal markers. CONCLUSIONS/SIGNIFICANCE: The transplantation of anterior specified NPs may improve optic nerve injury through neuroprotection and differentiation into neuronal lineages. These NPs possibly provide a promising new therapeutic approach for traumatic optic nerve injuries and loss of RGCs caused by other diseases.

  12. Human factors in training

    International Nuclear Information System (INIS)

    Dutton, J.W.; Brown, W.R.


    The Human Factors concept is a focused effort directed at those activities which require human involvement. Training is, by its nature, an activity totally dependent on the Human Factor. This paper identifies several concerns significant to training situations and discusses how Human Factor awareness can increase the quality of learning. Psychology in the training arena is applied Human Factors. Training is a method of communication represented by sender, medium, and receiver. Two-thirds of this communications model involves the human element directly

  13. Human-machine interactions (United States)

    Forsythe, J Chris [Sandia Park, NM; Xavier, Patrick G [Albuquerque, NM; Abbott, Robert G [Albuquerque, NM; Brannon, Nathan G [Albuquerque, NM; Bernard, Michael L [Tijeras, NM; Speed, Ann E [Albuquerque, NM


    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  14. The Human/Machine Humanities: A Proposal

    Directory of Open Access Journals (Sweden)

    Ollivier Dyens


    Full Text Available What does it mean to be human in the 21st century? The pull of engineering on every aspect of our lives, the impact of machines on how we represent ourselves, the influence of computers on our understanding of free-will, individuality and species, and the effect of microorganisms on our behaviour are so great that one cannot discourse on humanity and humanities without considering their entanglement with technology and with the multiple new dimensions of reality that it opens up. The future of humanities should take into account AI, bacteria, software, viruses (both organic and inorganic, hardware, machine language, parasites, big data, monitors, pixels, swarms systems and the Internet. One cannot think of humanity and humanities as distinct from technology anymore.

  15. Special Section: Human Rights (United States)

    Frydenlund, Knut; And Others


    Eleven articles examine human rights in Europe. Topics include unemployment, human rights legislation, role of the Council of Europe in promoting human rights, labor unions, migrant workers, human dignity in industralized societies, and international violence. Journal available from Council of Europe, Directorate of Press and Information, 67006…

  16. Human factor reliability program

    International Nuclear Information System (INIS)

    Knoblochova, L.


    The human factor's reliability program was at Slovenske elektrarne, a.s. (SE) nuclear power plants. introduced as one of the components Initiatives of Excellent Performance in 2011. The initiative's goal was to increase the reliability of both people and facilities, in response to 3 major areas of improvement - Need for improvement of the results, Troubleshooting support, Supporting the achievement of the company's goals. The human agent's reliability program is in practice included: - Tools to prevent human error; - Managerial observation and coaching; - Human factor analysis; -Quick information about the event with a human agent; -Human reliability timeline and performance indicators; - Basic, periodic and extraordinary training in human factor reliability(authors)

  17. Economics of human trafficking. (United States)

    Wheaton, Elizabeth M; Schauer, Edward J; Galli, Thomas V


    Because freedom of choice and economic gain are at the heart of productivity, human trafficking impedes national and international economic growth. Within the next 10 years, crime experts expect human trafficking to surpass drug and arms trafficking in its incidence, cost to human well-being, and profitability to criminals (Schauer and Wheaton, 2006: 164-165). The loss of agency from human trafficking as well as from modern slavery is the result of human vulnerability (Bales, 2000: 15). As people become vulnerable to exploitation and businesses continually seek the lowest-cost labour sources, trafficking human beings generates profit and a market for human trafficking is created. This paper presents an economic model of human trafficking that encompasses all known economic factors that affect human trafficking both across and within national borders. We envision human trafficking as a monopolistically competitive industry in which traffickers act as intermediaries between vulnerable individuals and employers by supplying differentiated products to employers. In the human trafficking market, the consumers are employers of trafficked labour and the products are human beings. Using a rational-choice framework of human trafficking we explain the social situations that shape relocation and working decisions of vulnerable populations leading to human trafficking, the impetus for being a trafficker, and the decisions by employers of trafficked individuals. The goal of this paper is to provide a common ground upon which policymakers and researchers can collaborate to decrease the incidence of trafficking in humans.

  18. Boundaries of Humanities: Writing Medical Humanities (United States)

    Bolton, Gillie


    Literature and medicine is a discipline within medical humanities, which challenges medicine to reconfigure its scientific model to become interdisciplinary, and be disciplined by arts and humanities as well as science. The psychological, emotional, spiritual and physical are inextricably linked in people, inevitably entailing provisionality,…

  19. Human algorithmic stability and human Rademacher complexity

    NARCIS (Netherlands)

    Vahdat, Mehrnoosh; Oneto, L.; Ghio, A; Anguita, D.; Funk, M.; Rauterberg, G.W.M.


    In Machine Learning (ML), the learning process of an algo- rithm given a set of evidences is studied via complexity measures. The way towards using ML complexity measures in the Human Learning (HL) domain has been paved by a previous study, which introduced Human Rademacher Complexity (HRC): in this

  20. Human errors and mistakes

    International Nuclear Information System (INIS)

    Wahlstroem, B.


    Human errors have a major contribution to the risks for industrial accidents. Accidents have provided important lesson making it possible to build safer systems. In avoiding human errors it is necessary to adapt the systems to their operators. The complexity of modern industrial systems is however increasing the danger of system accidents. Models of the human operator have been proposed, but the models are not able to give accurate predictions of human performance. Human errors can never be eliminated, but their frequency can be decreased by systematic efforts. The paper gives a brief summary of research in human error and it concludes with suggestions for further work. (orig.)

  1. Defense Human Resources Activity > PERSEREC (United States)

    Skip to main content (Press Enter). Toggle navigation Defense Human Resources Activity Search Search Defense Human Resources Activity: Search Search Defense Human Resources Activity: Search Defense Human Resources Activity U.S. Department of Defense Defense Human Resources Activity Overview

  2. Evaluating human genetic diversity

    National Research Council Canada - National Science Library

    This book assesses the scientific value and merit of research on human genetic differences--including a collection of DNA samples that represents the whole of human genetic diversity--and the ethical...

  3. Human Exposure and Health (United States)

    The ROE is divided into 5 themes: Air, Water, Land, Human Exposure and Health and Ecological Condition. From these themes, the report indicators address fundamental questions that the ROE attempts to answer. For human health there are 3 questions.


    Directory of Open Access Journals (Sweden)



    Full Text Available The purpose of this paper is to analyze human resources in terms of quantitative and qualitative side with special focus on the human capital accumulation influence. The paper examines the human resources trough human capital accumulation in terms of modern theory of human resources, educational capital, health, unemployment and migration. The findings presented in this work are based on theoretical economy publications and data collected from research materials. Sources of information include: documents from organizations - the EUROSTAT, INSSE - studies from publications, books, periodicals, and the Internet. The paper describes and analyzes human resources characteristics, human resource capacities, social and economic benefits of human capital accumulation based on economy, and the government plans and policies on health, education and labor market.

  5. Human bites (image) (United States)

    Human bites present a high risk of infection. Besides the bacteria which can cause infection, there is ... the wound extends below the skin. Anytime a human bite has broken the skin, seek medical attention.

  6. HPV (Human Papillomavirus) (United States)

    ... Consumers Consumer Information by Audience For Women HPV (human papillomavirus) Share Tweet Linkedin Pin it More sharing ... Español In Chamorro In Urdu In Vietnamese HPV (human papillomavirus) is a sexually transmitted virus. It is ...

  7. Human Papillomavirus (HPV) Vaccine (United States)

    Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...

  8. Human Parainfluenza Viruses (United States)

    ... Search Form Controls Cancel Submit Search The CDC Human Parainfluenza Viruses (HPIVs) Note: Javascript is disabled or ... . Recommend on Facebook Tweet Share Compartir Human parainfluenza viruses (HPIVs) commonly cause respiratory illnesses in ...

  9. Human Use Index (Future) (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  10. Human Use Index (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  11. Human papillomavirus molecular biology. (United States)

    Harden, Mallory E; Munger, Karl

    Human papillomaviruses are small DNA viruses with a tropism for squamous epithelia. A unique aspect of human papillomavirus molecular biology involves dependence on the differentiation status of the host epithelial cell to complete the viral lifecycle. A small group of these viruses are the etiologic agents of several types of human cancers, including oral and anogenital tract carcinomas. This review focuses on the basic molecular biology of human papillomaviruses. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Human Computer Music Performance


    Dannenberg, Roger B.


    Human Computer Music Performance (HCMP) is the study of music performance by live human performers and real-time computer-based performers. One goal of HCMP is to create a highly autonomous artificial performer that can fill the role of a human, especially in a popular music setting. This will require advances in automated music listening and understanding, new representations for music, techniques for music synchronization, real-time human-computer communication, music generation, sound synt...

  13. Humanities Review Journal

    African Journals Online (AJOL)

    Humanities Review Journal is published in June and December by Humanities Research Forum. The Journal publishes original, well-researched papers, review essays, interviews, resume, and commentaries, which offer new insights into the various disciplines in the Humanities. The focus is on issues about Africa.

  14. Humanity at the Edge

    DEFF Research Database (Denmark)

    Svendsen, Mette N.; Gjødsbøl, Iben M.; Dam, Mie S.


    At the heart of anthropology and the social sciences lies a notion of human existence according to which humans and animals share the basic need for food, but only humans have the capacity for morality. Based on fieldwork in a pig laboratory, a neonatal intensive care unit (NICU), and a dementia ...

  15. Human Document Project

    NARCIS (Netherlands)

    de Vries, Jeroen; Abelmann, Leon; Manz, A; Elwenspoek, Michael Curt


    “The Human Document Project‿ is a project which tries to answer all of the questions related to preserving information about the human race for tens of generations of humans to come or maybe even for a future intelligence which can emerge in the coming thousands of years. This document mainly

  16. Esprit: A Humanities Magazine. (United States)

    Parker, Donald G.; Capella, Barry John

    In March 1984, the first issue of "Esprit," a semi-annual humanities magazine for the 56 two-year colleges in New York State, was published. The magazine seeks to confront the apparent decline of student interest in the humanities, community doubts about the relevance of the humanities, and the seeming indifference to the special truths…

  17. A Human Rights Glossary. (United States)

    Flowers, Nancy


    Presents a human rights glossary that includes definitions of basic terms, treaties, charters, and groups/organizations that have been featured in previous articles in this edition of "Update on Law-Related Education"; the human rights terms have been compiled as part of the celebration of the Universal Declaration of Human Rights…

  18. Has Human Evolution Stopped?

    Directory of Open Access Journals (Sweden)

    Alan R. Templeton


    Full Text Available It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

  19. Human Machine Learning Symbiosis (United States)

    Walsh, Kenneth R.; Hoque, Md Tamjidul; Williams, Kim H.


    Human Machine Learning Symbiosis is a cooperative system where both the human learner and the machine learner learn from each other to create an effective and efficient learning environment adapted to the needs of the human learner. Such a system can be used in online learning modules so that the modules adapt to each learner's learning state both…

  20. A scalable and deformable stylized model of the adult human eye for radiation dose assessment. (United States)

    El Basha, Daniel; Furuta, Takuya; Iyer, Siva S R; Bolch, Wesley E


    With recent changes in the recommended annual limit on eye lens exposures to ionizing radiation, there is considerable interest in predictive computational dosimetry models of the human eye and its various ocular structures including the crystalline lens, ciliary body, cornea, retina, optic nerve, and central retinal artery. Computational eye models to date have been constructed as stylized models, high-resolution voxel models, and polygon mesh models. Their common feature, however, is that they are typically constructed of nominal size and of a roughly spherical shape associated with the emmetropic eye. In this study, we present a geometric eye model that is both scalable (allowing for changes in eye size) and deformable (allowing for changes in eye shape), and that is suitable for use in radiation transport studies of ocular exposures and radiation treatments of eye disease. The model allows continuous and variable changes in eye size (axial lengths from 20 to 26 mm) and eye shape (diopters from -12 to +6). As an explanatory example of its use, five models (emmetropic eyes of small, average, and large size, as well as average size eyes of -12D and +6D) were constructed and subjected to normally incident beams of monoenergetic electrons and photons, with resultant energy-dependent dose coefficients presented for both anterior and posterior eye structures. Electron dose coefficients were found to vary with changes to both eye size and shape for the posterior eye structures, while their values for the eye crystalline lens were found to be sensitive to changes in only eye size. No dependence upon eye size or eye shape was found for photon dose coefficients at energies below 2 MeV. Future applications of the model can include more extensive tabulations of dose coefficients to all ocular structures (not only the lens) as a function of eye size and shape, as well as the assessment of x-ray therapies for ocular disease for patients with non-emmetropic eyes. © 2018

  1. A scalable and deformable stylized model of the adult human eye for radiation dose assessment (United States)

    El Basha, Daniel; Furuta, Takuya; Iyer, Siva S. R.; Bolch, Wesley E.


    With recent changes in the recommended annual limit on eye lens exposures to ionizing radiation, there is considerable interest in predictive computational dosimetry models of the human eye and its various ocular structures including the crystalline lens, ciliary body, cornea, retina, optic nerve, and central retinal artery. Computational eye models to date have been constructed as stylized models, high-resolution voxel models, and polygon mesh models. Their common feature, however, is that they are typically constructed of nominal size and of a roughly spherical shape associated with the emmetropic eye. In this study, we present a geometric eye model that is both scalable (allowing for changes in eye size) and deformable (allowing for changes in eye shape), and that is suitable for use in radiation transport studies of ocular exposures and radiation treatments of eye disease. The model allows continuous and variable changes in eye size (axial lengths from 20 to 26 mm) and eye shape (diopters from  ‑12 to  +6). As an explanatory example of its use, five models (emmetropic eyes of small, average, and large size, as well as average size eyes of  ‑12D and  +6D) were constructed and subjected to normally incident beams of monoenergetic electrons and photons, with resultant energy-dependent dose coefficients presented for both anterior and posterior eye structures. Electron dose coefficients were found to vary with changes to both eye size and shape for the posterior eye structures, while their values for the crystalline lens were found to be sensitive to changes in only eye size. No dependence upon eye size or eye shape was found for photon dose coefficients at energies below 2 MeV. Future applications of the model can include more extensive tabulations of dose coefficients to all ocular structures (not only the lens) as a function of eye size and shape, as well as the assessment of x-ray therapies for ocular disease for patients with non

  2. Skin and the non-human human

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk


    The article puts forward an aesthetic and psychoanalytic analysis of Titian's painting, The Flaying of Marsyas, arguing that the painting is a reflection on the human subject as a being constituted by skin and by a core of non-humanity. The analysis is partly an answer to Melanie Hart's (2007) ar...... of the 'Muselmann', and Anton Ehrenzweig's psychoanalytic theory of artistic creation. Whereas Hart is focusing on form and colour, I also turn my attention towards the texture of the painting....

  3. Universe, human immortality and future human evaluation

    CERN Document Server

    Bolonkin, Alexander


    This book debates the universe, the development of new technologies in the 21st century and the future of the human race. Dr Bolonkin shows that a human soul is only the information in a person's head. He offers a new unique method for re-writing the main brain information in chips without any damage to the human brain. This is the scientific prediction of the non-biological (electronic) civilization and immortality of the human being. Such a prognosis is predicated upon a new law, discovered by the author, for the development of complex systems. According to this law, every self-copying system tends to be more complex than the previous system, provided that all external conditions remain the same. The consequences are disastrous: humanity will be replaced by a new civilization created by intellectual robots (which Dr Bolonkin refers to as "E-humans" and "E-beings"). These creatures, whose intellectual and mechanical abilities will far exceed those of man, will require neither food nor oxygen to sustain their...

  4. Modeling Human Leukemia Immunotherapy in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Jinxing Xia


    Full Text Available The currently available human tumor xenograft models permit modeling of human cancers in vivo, but in immunocompromised hosts. Here we report a humanized mouse (hu-mouse model made by transplantation of human fetal thymic tissue plus hematopoietic stem cells transduced with a leukemia-associated fusion gene MLL-AF9. In addition to normal human lymphohematopoietic reconstitution as seen in non-leukemic hu-mice, these hu-mice showed spontaneous development of B-cell acute lymphoblastic leukemia (B-ALL, which was transplantable to secondary recipients with an autologous human immune system. Using this model, we show that lymphopenia markedly improves the antitumor efficacy of recipient leukocyte infusion (RLI, a GVHD-free immunotherapy that induces antitumor responses in association with rejection of donor chimerism in mixed allogeneic chimeras. Our data demonstrate the potential of this leukemic hu-mouse model in modeling leukemia immunotherapy, and suggest that RLI may offer a safe treatment option for leukemia patients with severe lymphopenia.

  5. Transfer of Natrialba asiatica B1T to Natrialba taiwanensis sp. nov. and description of Natrialba aegyptiaca sp. nov., a novel extremely halophilic, aerobic, non-pigmented member of the Archaea from Egypt that produces extracellular poly(glutamic acid). (United States)

    Hezayen, F F; Rehm, B H; Tindall, B J; Steinbüchel, A


    A novel extremely halophilic member of the Archaea, strain 40T, was isolated from Egypt (Aswan). This isolate requires at least 1.6 M sodium chloride for growth and exhibits optimal growth between 37 and 42 degrees C. Determination of the entire 16S rRNA gene sequence revealed the highest similarity to the type strain of Natrialba asiatica (> 99%). Polar lipid analysis indicated that strain 40T and Natrialba asiatica have essentially identical compositions, indicating that the former is a member of genus Natrialba. However, physiological and biochemical data provided evidence that Natrialba asiatica strains B1T and 172P1T, as well as strain 40T, are sufficiently different to be divided in three different species. The G+C content of strain 40T was 61.5+/-0.6 mol%. In addition, DNA-DNA hybridization data supported the placement of the isolate in a new species in the genus Natrialba, Natrialba aegyptiaca sp. nov., and indicated that Natrialba asiatica strain B1T should also be placed in a separate species, Natrialba taiwanensis sp. nov. Morphological studies of strain 40T indicated clearly that this isolate appears in three completely different cell shapes (cocci, rods, tetrads) under different conditions of growth, including different sodium chloride concentrations and different growth temperatures. Another interesting property of strain 40T is the ability to produce an extracellular polymer, which was found to be composed predominantly of glutamic acid (85% w/w), representing poly(glutamic acid), carbohydrates (12.5% w/w) and unidentified compounds (2.5% w/w). Among the Archaea, production of an extracellular polysaccharide has been described for some members of the genera Haloferax and Haloarcula.

  6. Rethinking medical humanities. (United States)

    Chiapperino, Luca; Boniolo, Giovanni


    This paper questions different conceptions of Medical Humanities in order to provide a clearer understanding of what they are and why they matter. Building upon former attempts, we defend a conception of Medical Humanities as a humanistic problem-based approach to medicine aiming at influencing its nature and practice. In particular, we discuss three main conceptual issues regarding the overall nature of this discipline: (i) a problem-driven approach to Medical Humanities; (ii) the need for an integration of Medical Humanities into medicine; (iii) the methodological requirements that could render Medical Humanities an effective framework for medical decision-making.

  7. [Human factors in medicine]. (United States)

    Lazarovici, M; Trentzsch, H; Prückner, S


    The concept of human factors is commonly used in the context of patient safety and medical errors, all too often ambiguously. In actual fact, the term comprises a wide range of meanings from human-machine interfaces through human performance and limitations up to the point of working process design; however, human factors prevail as a substantial cause of error in complex systems. This article presents the full range of the term human factors from the (emergency) medical perspective. Based on the so-called Swiss cheese model by Reason, we explain the different types of error, what promotes their emergence and on which level of the model error prevention can be initiated.

  8. Effective silencing of ENaC by siRNA delivered with epithelial-targeted nanocomplexes in human cystic fibrosis cells and in mouse lung. (United States)

    Tagalakis, Aristides D; Munye, Mustafa M; Ivanova, Rositsa; Chen, Hanpeng; Smith, Claire M; Aldossary, Ahmad M; Rosa, Luca Z; Moulding, Dale; Barnes, Josephine L; Kafetzis, Konstantinos N; Jones, Stuart A; Baines, Deborah L; Moss, Guy W J; O'Callaghan, Christopher; McAnulty, Robin J; Hart, Stephen L


    Loss of the cystic fibrosis transmembrane conductance regulator in cystic fibrosis (CF) leads to hyperabsorption of sodium and fluid from the airway due to upregulation of the epithelial sodium channel (ENaC). Thickened mucus and depleted airway surface liquid (ASL) then lead to impaired mucociliary clearance. ENaC regulation is thus a promising target for CF therapy. Our aim was to develop siRNA nanocomplexes that mediate effective silencing of airway epithelial ENaC in vitro and in vivo with functional correction of epithelial ion and fluid transport. We investigated translocation of nanocomplexes through mucus and their transfection efficiency in primary CF epithelial cells grown at air-liquid interface (ALI).Short interfering RNA (SiRNA)-mediated silencing was examined by quantitative RT-PCR and western analysis of ENaC. Transepithelial potential (V t ), short circuit current (I sc ), ASL depth and ciliary beat frequency (CBF) were measured for functional analysis. Inflammation was analysed by histological analysis of normal mouse lung tissue sections. Nanocomplexes translocated more rapidly than siRNA alone through mucus. Transfections of primary CF epithelial cells with nanocomplexes targeting αENaC siRNA, reduced αENaC and βENaC mRNA by 30%. Transfections reduced V t , the amiloride-sensitive I sc and mucus protein concentration while increasing ASL depth and CBF to normal levels. A single dose of siRNA in mouse lung silenced ENaC by approximately 30%, which persisted for at least 7 days. Three doses of siRNA increased silencing to approximately 50%. Nanoparticle-mediated delivery of ENaCsiRNA to ALI cultures corrected aspects of the mucociliary defect in human CF cells and offers effective delivery and silencing in vivo. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Computing the stresses and deformations of the human eye components due to a high explosive detonation using fluid-structure interaction model. (United States)

    Karimi, Alireza; Razaghi, Reza; Navidbakhsh, Mahdi; Sera, Toshihiro; Kudo, Susumu


    In spite the fact that a very small human body surface area is comprised by the eye, its wounds due to detonation have recently been dramatically amplified. Although many efforts have been devoted to measure injury of the globe, there is still a lack of knowledge on the injury mechanism due to Primary Blast Wave (PBW). The goal of this study was to determine the stresses and deformations of the human eye components, including the cornea, aqueous, iris, ciliary body, lens, vitreous, retina, sclera, optic nerve, and muscles, attributed to PBW induced by trinitrotoluene (TNT) explosion via a Lagrangian-Eulerian computational coupling model. Magnetic Resonance Imaging (MRI) was employed to establish a Finite Element (FE) model of the human eye according to a normal human eye. The solid components of the eye were modelled as Lagrangian mesh, while an explosive TNT, air domain, and aqueous were modelled using Arbitrary Lagrangian-Eulerian (ALE) mesh. Nonlinear dynamic FE simulations were accomplished using the explicit FE code, namely LS-DYNA. In order to simulate the blast wave generation, propagation, and interaction with the eye, the ALE formulation with Jones-Wilkins-Lee (JWL) equation defining the explosive material were employed. The results revealed a peak stress of 135.70kPa brought about by detonation upsurge on the cornea at the distance of 25cm. The highest von Mises stresses were observed on the sclera (267.3kPa), whereas the lowest one was seen on the vitreous body (0.002kPa). The results also showed a relatively high resultant displacement for the macula as well as a high variation for the radius of curvature for the cornea and lens, which can result in both macular holes, optic nerve damage and, consequently, vision loss. These results may have implications not only for understanding the value of stresses and strains in the human eye components but also giving an outlook about the process of PBW triggers damage to the eye. Copyright © 2016 Elsevier Ltd

  10. Integrated Environmental Modelling: Human decisions, human challenges (United States)

    Glynn, Pierre D.


    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  11. Human Respiratory Syncytial Virus and Human Metapneumovirus

    Directory of Open Access Journals (Sweden)

    Luciana Helena Antoniassi da Silva


    Full Text Available The human respiratory syncytial virus (hRSV and the human metapneumovírus (hMPV are main etiological agents of acute respiratory infections (ARI. The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV is the best characterized agent viral of this group, associated with respiratory diseases in lower respiratory tract. Recently, a new human pathogen belonging to the subfamily Pneumovirinae was identified, the human metapneumovirus (hMPV, which is structurally similar to the hRSV, in genomic organization, viral structure, antigenicity and clinical symptoms.  The subfamily Pneumovirinae contains two genera: genus Pneumovirus contains hRSV, the bovine (bRSV, as well as the ovine and caprine respiratory syncytial virus and pneumonia virus of mice, the second genus Metapneumovirus, consists of avian metapneumovirus (aMPV and human metapneumovirus (hMPV. In this work, we present a brief narrative review of the literature on important aspects of the biology, epidemiology and clinical manifestations of infections by two respiratory viruses.

  12. Bursty human dynamics

    CERN Document Server

    Karsai, Márton; Kaski, Kimmo


    This book provides a comprehensive overview on emergent bursty patterns in the dynamics of human behaviour. It presents common and alternative understanding of the investigated phenomena, and points out open questions worthy of further investigations. The book is structured as follows. In the introduction the authors discuss the motivation of the field, describe bursty phenomena in case of human behaviour, and relate it to other disciplines. The second chapter addresses the measures commonly used to characterise heterogeneous signals, bursty human dynamics, temporal paths, and correlated behaviour. These definitions are first introduced to set the basis for the discussion of the third chapter about the observations of bursty human patterns in the dynamics of individuals, dyadic interactions, and collective behaviour. The subsequent fourth chapter discusses the models of bursty human dynamics. Various mechanisms have been proposed about the source of the heterogeneities in human dynamics, which leads to the in...

  13. The Human Cell Atlas. (United States)

    Regev, Aviv; Teichmann, Sarah A; Lander, Eric S; Amit, Ido; Benoist, Christophe; Birney, Ewan; Bodenmiller, Bernd; Campbell, Peter; Carninci, Piero; Clatworthy, Menna; Clevers, Hans; Deplancke, Bart; Dunham, Ian; Eberwine, James; Eils, Roland; Enard, Wolfgang; Farmer, Andrew; Fugger, Lars; Göttgens, Berthold; Hacohen, Nir; Haniffa, Muzlifah; Hemberg, Martin; Kim, Seung; Klenerman, Paul; Kriegstein, Arnold; Lein, Ed; Linnarsson, Sten; Lundberg, Emma; Lundeberg, Joakim; Majumder, Partha; Marioni, John C; Merad, Miriam; Mhlanga, Musa; Nawijn, Martijn; Netea, Mihai; Nolan, Garry; Pe'er, Dana; Phillipakis, Anthony; Ponting, Chris P; Quake, Stephen; Reik, Wolf; Rozenblatt-Rosen, Orit; Sanes, Joshua; Satija, Rahul; Schumacher, Ton N; Shalek, Alex; Shapiro, Ehud; Sharma, Padmanee; Shin, Jay W; Stegle, Oliver; Stratton, Michael; Stubbington, Michael J T; Theis, Fabian J; Uhlen, Matthias; van Oudenaarden, Alexander; Wagner, Allon; Watt, Fiona; Weissman, Jonathan; Wold, Barbara; Xavier, Ramnik; Yosef, Nir


    The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

  14. Managing human performance

    International Nuclear Information System (INIS)

    Bishop, J.; LaRhette, R.


    Evaluating human error or human performance problems and correcting the root causes can help preclude recurrence. The Institute of Nuclear Power Operations (INPO), working with several members and participant utilities in an extended pilot program, has developed a nonpunitive program designed to identify, evaluate, and correct situations that cause human performance errors. The program is called the Human Performance Evaluation System (HPES). Its primary goal is to improve human reliability in overall nuclear plant operations by reducing human error through correction of the conditions that cause the errors. Workers at participating nuclear utilities are encouraged to report their errors and a specially trained plant coordinator investigates and recommends actions to correct the root causes of these errors

  15. Developing human technology curriculum

    Directory of Open Access Journals (Sweden)

    Teija Vainio


    Full Text Available During the past ten years expertise in human-computer interaction has shifted from humans interacting with desktop computers to individual human beings or groups of human beings interacting with embedded or mobile technology. Thus, humans are not only interacting with computers but with technology. Obviously, this shift should be reflected in how we educate human-technology interaction (HTI experts today and in the future. We tackle this educational challenge first by analysing current Master’s-level education in collaboration with two universities and second, discussing postgraduate education in the international context. As a result, we identified core studies that should be included in the HTI curriculum. Furthermore, we discuss some practical challenges and new directions for international HTI education.

  16. Human Respiratory Syncytial Virus and Human Metapneumovirus


    Luciana Helena Antoniassi da Silva; Fernando Rosado Spilki; Adriana Gut Lopes Riccetto; Emilio Elias Baracat; Clarice Weis Arns


    The human respiratory syncytial virus (hRSV) and the human metapneumovírus (hMPV) are main etiological agents of acute respiratory infections (ARI). The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV) is the best characterized agent viral of this group, associated with respiratory diseases in...

  17. Human intrusion: New ideas?

    International Nuclear Information System (INIS)

    Cooper, J.R.


    Inadvertent human intrusion has been an issue for the disposal of solid radioactive waste for many years. This paper discusses proposals for an approach for evaluating the radiological significance of human intrusion as put forward by ICRP with contribution from work at IAEA. The approach focuses on the consequences of the intrusion. Protective actions could, however, include steps to reduce the probability of human intrusion as well as the consequences. (author)

  18. Human reliability analysis

    International Nuclear Information System (INIS)

    Dougherty, E.M.; Fragola, J.R.


    The authors present a treatment of human reliability analysis incorporating an introduction to probabilistic risk assessment for nuclear power generating stations. They treat the subject according to the framework established for general systems theory. Draws upon reliability analysis, psychology, human factors engineering, and statistics, integrating elements of these fields within a systems framework. Provides a history of human reliability analysis, and includes examples of the application of the systems approach

  19. The human genome project

    International Nuclear Information System (INIS)

    Worton, R.


    The Human Genome Project is a massive international research project, costing 3 to 5 billion dollars and expected to take 15 years, which will identify the all the genes in the human genome - i.e. the complete sequence of bases in human DNA. The prize will be the ability to identify genes causing or predisposing to disease, and in some cases the development of gene therapy, but this new knowledge will raise important ethical issues

  20. Modern Human Capital Management


    Feldberger, Madita


    Title: Modern Human Capital Management Seminar date: 30th of May 2008 Course: Master thesis in Business Administration, 15 ECTS Authors: Madita Feldberger Supervisor: Lars Svensson Keywords: Human capital, SWOT Analysis, Strategic Map, Balanced Scorecard Research Problem: Despite of the success of Human Capital Management (HCM) in research it did not arrive yet in the HR departments of many companies. Numerous firms even have problems to set their strategic goals with focus on HR. The HR Bala...

  1. Options for human intrusion

    International Nuclear Information System (INIS)

    Bauser, M.; Williams, R.


    This paper addresses options for dealing with human intrusion in terms of performance requirements and repository siting and design requirements. Options are presented, along with the advantages and disadvantages of certain approaches. At the conclusion, a conceptual approach is offered emphasizing both the minimization of subjective judgements concerning future human activity, and specification of repository requirements to minimize the likelihood of human intrusion and any resulting, harmful effects should intrusion occur

  2. Human Engineering Procedures Guide (United States)


    Research Laboratory AFETR Air Force Eastern Test Range AFFTC Air Force Flight Test Center AFHRL Air Force Human Resources Laboratory AFR Air Force...performance requirements through the most effective use of man’s performance capability. 13 Human Engineering is one of five elements in the Human...applied judiciously and tailored to fit * the program or program phase and the acquisition strategy to achieve cost effective acquisition and life cycle

  3. Human babesiosis: Recent discoveries


    Mitrović Sanja M.; Kranjčić-Zec Ivana F.; Arsić-Arsenijević Valentina S.; Džamić Aleksandar M.; Radonjić Ivana V.


    Introduction Babesiosis is caused by intraerythrocytic parasites of the genus Babesia, which is a common animal infection worldwide. This protozoa requires both a competent vertebrate and a nonvertebrate host (Ixodes sp. etc.) to maintain the transmission cycle. Human babesiosis Human babesiosis is predominantly caused by Babesia microti (rodent-borne piroplasm, an emerging zoonosis in humans in North America) and by Babesia divergens (bovine pathogen, in Europe). Occasionally, infection in A...

  4. Dogs catch human yawns


    Joly-Mascheroni, Ramiro M; Senju, Atsushi; Shepherd, Alex J


    This study is the first to demonstrate that human yawns are possibly contagious to domestic dogs (Canis familiaris). Twenty-nine dogs observed a human yawning or making control mouth movements. Twenty-one dogs yawned when they observed a human yawning, but control mouth movements did not elicit yawning from any of them. The presence of contagious yawning in dogs suggests that this phenomenon is not specific to primate species and may indicate that dogs possess the capacity for a rudimentary f...

  5. Human Performance Research Center (United States)

    Federal Laboratory Consortium — Biochemistry:Improvements in energy metabolism, muscular strength and endurance capacity have a basis in biochemical and molecular adaptations within the human body....

  6. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo


    Human studies in the past three decades have provided us with an emerging understanding of how cortical and spinal networks collaborate to ensure the vast repertoire of human behaviors. We differ from other animals in having direct cortical connections to spinal motoneurons, which bypass spinal...... the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. Expected final online...

  7. Human Capital Overview

    National Research Council Canada - National Science Library

    McCarthy, Ellen E


    ...: To provide an agile, adaptive, integrated, and innovative defense intelligence workforce through a deliberate process identifying, implementing, and directing human capital organizational, doctrinal...

  8. Developing Human Resources through Actualizing Human Potential (United States)

    Clarken, Rodney H.


    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  9. Challenges for Virtual Humans in Human Computing

    NARCIS (Netherlands)

    Reidsma, Dennis; Ruttkay, Z.M.; Huang, T; Nijholt, Antinus; Pantic, Maja; Pentland, A.

    The vision of Ambient Intelligence (AmI) presumes a plethora of embedded services and devices that all endeavor to support humans in their daily activities as unobtrusively as possible. Hardware gets distributed throughout the environment, occupying even the fabric of our clothing. The environment

  10. Human trafficking in Germany: strengthening victim's human rights


    Follmar-Otto, Petra; Rabe, Heike


    The first study - "A human rights approach against human trafficking - International obligations and the status of implementation in Germany" - analyses how the prohibition of human trafficking and the resulting state obligations are anchored in human rights. The more recent specialised international agreements on human trafficking and law-making in the European Union are then presented. The emphasis is on the Council of Europe Convention, which professes to treat human trafficking in a human...

  11. Human Rights, History of

    NARCIS (Netherlands)

    de Baets, Antoon; Wright, James


    In this article, six basic debates about human rights are clarified from a historical perspective: the origin of human rights as moral rights connected to the natural law doctrine and opposed to positive rights; the wave of criticism of their abstract and absolute character by nineteenth-century

  12. Rationality in Human Movement. (United States)

    O'Brien, Megan K; Ahmed, Alaa A


    It long has been appreciated that humans behave irrationally in economic decisions under risk: they fail to objectively consider uncertainty, costs, and rewards and instead exhibit risk-seeking or risk-averse behavior. We hypothesize that poor estimates of motor variability (influenced by motor task) and distorted probability weighting (influenced by relevant emotional processes) contribute to characteristic irrationality in human movement decisions.

  13. Human-centred Governance

    DEFF Research Database (Denmark)

    Bason, Christian


    Design approaches are now being applied all over the world as a powerful approach to innovating public policies and services. Christian Bason, author of Leading public design: Discovering human-centred governance, argues that by bringing design methods into play, public managers can lead change...... with citizens at the centre, and discover a new model for steering public organisations: human-centred governance....

  14. Translating the human microbiome

    NARCIS (Netherlands)

    Brown, J.; Vos, de W.M.; Distefano, P.S.; Doré, J.; Huttenhower, C.; Knight, R.; Lawley, T.D.; Raes, J.; Turnbaugh, P.


    Over the past decade, an explosion of descriptive analyses from initiatives, such as the Human Microbiome Project (HMP) and the MetaHIT project, have begun to delineate the human microbiome. Inhabitants of the intestinal tract, nasal passages, oral cavities, skin, gastrointestinal tract and

  15. Incorporating Human Interindividual Biotransformation ... (United States)

    The protection of sensitive individuals within a population dictates that measures other than central tendencies be employed to estimate risk. The refinement of human health risk assessments for chemicals metabolized by the liver to reflect data on human variability can be accomplished through (1) the characterization of enzyme expression in large banks of human liver samples, (2) the employment of appropriate techniques for the quantification and extrapolation of metabolic rates derived in vitro, and (3) the judicious application of physiologically based pharmacokinetic (PBPK) modeling. While in vitro measurements of specific biochemical reactions from multiple human samples can yield qualitatively valuable data on human variance, such measures must be put into the perspective of the intact human to yield the most valuable predictions of metabolic differences among humans. For quantitative metabolism data to be the most valuable in risk assessment, they must be tied to human anatomy and physiology, and the impact of their variance evaluated under real exposure scenarios. For chemicals metabolized in the liver, the concentration of parent chemical in the liver represents the substrate concentration in the MichaelisMenten description of metabolism. Metabolic constants derived in vitro may be extrapolated to the intact liver, when appropriate conditions are met. Metabolic capacity Vmax; the maximal rate of the reaction) can be scaled directly to the concentration

  16. Human Powered Centrifuge (United States)

    Mulenburg, Gerald M. (Inventor); Vernikos, Joan (Inventor)


    A human powered centrifuge has independently established turntable angular velocity and human power input. A control system allows excess input power to be stored as electric energy in a battery or dissipated as heat through a resistors. In a mechanical embodiment, the excess power is dissipated in a friction brake.

  17. Kinship and Human Evolution

    DEFF Research Database (Denmark)

    Bergendorff, Steen

    This book offers a exiting new explanation of human evolution. Based on insight from Anthropology is shows that human became 'cultured' beings capable of symbolic thought by developing rasting kinship based between groups that could not other wise survive in the harah climate condition during...

  18. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  19. Fungi that Infect Humans. (United States)

    Köhler, Julia R; Hube, Bernhard; Puccia, Rosana; Casadevall, Arturo; Perfect, John R


    Fungi must meet four criteria to infect humans: growth at human body temperatures, circumvention or penetration of surface barriers, lysis and absorption of tissue, and resistance to immune defenses, including elevated body temperatures. Morphogenesis between small round, detachable cells and long, connected cells is the mechanism by which fungi solve problems of locomotion around or through host barriers. Secretion of lytic enzymes, and uptake systems for the released nutrients, are necessary if a fungus is to nutritionally utilize human tissue. Last, the potent human immune system evolved in the interaction with potential fungal pathogens, so few fungi meet all four conditions for a healthy human host. Paradoxically, the advances of modern medicine have made millions of people newly susceptible to fungal infections by disrupting immune defenses. This article explores how different members of four fungal phyla use different strategies to fulfill the four criteria to infect humans: the Entomophthorales, the Mucorales, the Ascomycota, and the Basidiomycota. Unique traits confer human pathogenic potential on various important members of these phyla: pathogenic Onygenales comprising thermal dimorphs such as Histoplasma and Coccidioides ; the Cryptococcus spp. that infect immunocompromised as well as healthy humans; and important pathogens of immunocompromised patients- Candida , Pneumocystis , and Aspergillus spp. Also discussed are agents of neglected tropical diseases important in global health such as mycetoma and paracoccidiomycosis and common pathogens rarely implicated in serious illness such as dermatophytes. Commensalism is considered, as well as parasitism, in shaping genomes and physiological systems of hosts and fungi during evolution.

  20. Global Journal of Humanities

    African Journals Online (AJOL)

    Journal Homepage Image. Global Journal of Humanities is aimed at promoting reasearch in all areas of Humanities including philosophy, languages, linguistics, literature, history, fine/applied arts, theater arts, architecture, etc. Visit the Global Journal Series website here: ...

  1. Evaluating the Humanities (United States)

    Brody, Howard


    How can one measure the value of teaching the humanities? The problem of assessment and accountability is prominent today, of course, in secondary and higher education. It is perhaps even more acute for those who teach the humanities in nontraditional settings, such as medical and other professional schools. The public assumes that academes can…

  2. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei


    BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  3. Human Resource Construction

    Institute of Scientific and Technical Information of China (English)


    Centering on strategic objective of reform and development,CIAE formulated its objectives in human resource construction for the 13th Five-year Plan period,and achieved new apparent progress in human resource construction in 2015.1 Implementation of"LONGMA Project"

  4. Dynamics of human movement

    NARCIS (Netherlands)

    Koopman, Hubertus F.J.M.


    The part of (bio)mechanics that studies the interaction of forces on the human skeletal system and its effect on the resulting movement is called rigid body dynamics. Some basic concepts are presented: A mathematical formulation to describe human movement and how this relates on the mechanical loads

  5. Biodemography of human ageing

    DEFF Research Database (Denmark)

    Vaupel, James W


    Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems...

  6. Human Intestinal Spirochaetosis

    NARCIS (Netherlands)

    Westerman, L.J.


    Human intestinal spirochaetosis is a condition of the colon that is characterized by the presence of spirochaetes attached to the mucosal cells of the colon. These spirochaetes belong to the family Brachyspiraceae and two species are known to occur in humans: Brachyspira aalborgi and Brachyspira

  7. Human migraine models

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg


    , which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible...

  8. Manage "Human Capital" Strategically (United States)

    Odden, Allan


    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  9. Introduction to human factors

    International Nuclear Information System (INIS)

    Winters, J.M.


    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems

  10. Teaching Human Rights Law. (United States)

    Berman, Howard R.


    The international community has developed a system of human rights law relevant to many areas of legal encounter, which American law schools have been slow to incorporate into curricula. Teaching human rights law provides an opportunity for law schools to enrich the learning process and contribute creatively to the respect for rights in society.…

  11. Humane Education Projects Handbook. (United States)

    Junior League of Ogden, UT.

    This handbook was developed to promote interest in humane education and to encourage the adoption of humane education projects. Although specifically designed to assist Junior Leagues in developing such projects, the content should prove valuable to animal welfare organizations, zoos, aquariums, nature centers, and other project-oriented groups…

  12. Human Mind Maps (United States)

    Glass, Tom


    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  13. Urbanization and human rights

    NARCIS (Netherlands)

    Mihr, A.

    Urban governance on the basis of human rights can help to set up problem solving mechanisms to guarantee social peace, economic growth and political participation.If states both integrate more in international or regional human rights regime and give more autonomy to urban governments and local

  14. The Human Technology

    DEFF Research Database (Denmark)

    Fausing, Bent

     Bent Fausing  "The Humane Technology", abstract (for The Two Cultures: Balancing Choices and Effects Oxford University July 20-26, 2008). The paper will investigate the use of technology in everyday aesthetics such as TV-commercials for mobile phones for Nokia, which slogan is, as it is well known......, "Nokia - connecting people". Which function does this technology get in narratives, images, interactions and affects here?      The mobile phone and its digital camera are depicted as being able to make a unique human presence and interaction. The medium, the technology is a necessary helper to get...... towards this very special and lost humanity. Without the technology, no special humanity is the prophecy. This personification or anthropomorphism is important for the branding of new technology. The technology is seen as creating a technotranscendens towards a more qualified humanity, which is in contact...

  15. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei


    BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogeno...... of the solutions used in the study nor was it present as a residual material in blank HPLC runs. CONCLUSIONS: Morphine is present in human gliomas, suggesting that it may exert an action that effects tumour physiology/pathology.......BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  16. The human cell atlas

    DEFF Research Database (Denmark)

    Regev, Aviv; Teichmann, Sarah A.; Lander, Eric S.


    The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international...... collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells...... in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early...

  17. UN human rights council

    Directory of Open Access Journals (Sweden)

    Vuksanović Mlrjana


    Full Text Available The paper deals with the structure, mechanisms, practices and perspectives of the Human Rights Council, the UN body that, at universal level is the most important body in this area. Introductory section provides for a brief overview of the origins of human rights and the work of the Commission on Human Rights, in whose jurisdiction were questions of human rights before the establishment of the Council. After the introductory section the author gives an analysis of the structure, objectives, mandate and main procedures for the protection of human rights within the united Nations. In the final section the authorpoints out the advantages of this authority and criticism addressed to it, with emphasis on the possibility and the need for its reform.

  18. Waste - the human factor

    International Nuclear Information System (INIS)

    McLaren, D.J.


    Waste is a human concept, referring to things that have no use to human beings and arising entirely from human activities. It is the useless residue of any human process that affects the economy or environment. The changes brought about by the industrial revolution are enormous; fossil fuels, not just photosynthesis, now provide energy and wastes at rates far exceeding the capacity of the ecosystem to absorb or recycle. Three major problems face the Planet: accelerated population growth, accelerated use of resources for energy and industry, and the disproportionate use of resources and waste between the northern and southern parts of the Planet. Knowledge and science are in a position to provide both human creativity and the directed technology to take remedial action and rediscover harmony between nature and mankind. Only social and political will is lacking

  19. Managing human performance

    International Nuclear Information System (INIS)

    Strucic, M.; Kavsek, D.


    Human performance remains a significant factor for management attention not only from a reactor safety perspective, but also from a financial one. Recent significant events analysis shows that human errors are still dominant causes and contributors to them. An analysis of significant events in nuclear industry occurred through 15-years period revealed that three of four significant events were triggered by human error, although the number of events have dropped by more than a factor of four. A number of human performance breakdowns occurred in the application of errorprevention techniques. These included a lack of pre-job briefs, inadequate turnover of tasks, ineffective use of peer checking, inadequate procedure adherence, and failure to apply a questioning attitude when unexpected changes were encountered in the task. Attempts by the industry to improve human performance have traditionally focused at the worker level. However, human error occurs within the context of the organization, which can either foster or resist human error. The greatest room for improvement lies not only in the continued improvement of front-line worker performance but more so in the identification and elimination of weaknesses in the organizational and managerial domains that contributes to worker performance at the job site. Based on mentioned analysis, other industrial sources and own operating experience, NPP Krsko is paying more attention to improve human performance among own as well as contractor workers. Through series of programs and activities, such as Reactivity Management Program, Safety Culture Program, Self-assessment Program, Corrective Action Program, Plant Performance Monitoring Program, developed in last few years, and through new procedures, written guides and publications, training and management efforts, number of human errors is going to be reduced. Involvement of higher levels of NPP Krsko organization in promotion and use of Human Performance techniques is

  20. Digital Human Modeling (United States)

    Dischinger, H. Charles, Jr.


    The development of models to represent human characteristics and behaviors in human factors is broad and general. The term "model" can refer to any metaphor to represent any aspect of the human; it is generally used in research to mean a mathematical tool for the simulation (often in software, which makes the simulation digital) of some aspect of human performance and for the prediction of future outcomes. This section is restricted to the application of human models in physical design, e.g., in human factors engineering. This design effort is typically human interface design, and the digital models used are anthropometric. That is, they are visual models that are the physical shape of humans and that have the capabilities and constraints of humans of a selected population. They are distinct from the avatars used in the entertainment industry (movies, video games, and the like) in precisely that regard: as models, they are created through the application of data on humans, and they are used to predict human response; body stresses workspaces. DHM enable iterative evaluation of a large number of concepts and support rapid analysis, as compared with use of physical mockups. They can be used to evaluate feasibility of escape of a suited astronaut from a damaged vehicle, before launch or after an abort (England, et al., 2012). Throughout most of human spaceflight, little attention has been paid to worksite design for ground workers. As a result of repeated damage to the Space Shuttle which adversely affected flight safety, DHM analyses of ground assembly and maintenance have been developed over the last five years for the design of new flight systems (Stambolian, 2012, Dischinger and Dunn Jackson, 2014). The intent of these analyses is to assure the design supports the work of the ground crew personnel and thereby protect the launch vehicle. They help the analyst address basic human factors engineering questions: can a worker reach the task site from the work platform

  1. Human Milk Banking. (United States)

    Haiden, Nadja; Ziegler, Ekhard E


    Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. The largest group of recipients are premature infants who derive very substantial benefits from it. Human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. Milk banks collect, screen, store, process, and distribute human milk. Donating women usually nurse their own infants and have a milk supply that exceeds their own infants' needs. Donor women are carefully selected and are screened for HIV-1, HIV-2, human T-cell leukemia virus 1 and 2, hepatitis B, hepatitis C, and syphilis. In the milk bank, handling, storing, processing, pooling, and bacterial screening follow standardized algorithms. Heat treatment of human milk diminishes anti-infective properties, cellular components, growth factors, and nutrients. However, the beneficial effects of donor milk remain significant and donor milk is still highly preferable in comparison to formula. © 2017 S. Karger AG, Basel.

  2. Human factors information system

    International Nuclear Information System (INIS)

    Goodman, P.C.; DiPalo, C.A.


    Nuclear power plant safety is dependent upon human performance related to plant operations. To provide improvements in human performance, data collection and assessment play key roles. This paper reports on the Human factors Information System (HFIS) which is designed to meet the needs of the human factors specialists of the United States Nuclear Regulatory Commission. These specialists identify personnel errors and provide guidance designed to prevent such errors. HFIS is a simple and modular system designed for use on a personal computer. It is designed to contain four separate modules that provide information indicative of program or function effectiveness as well as safety-related human performance based on programmatic and performance data. These modules include the Human Factors Status module; the Regulatory Programs module; the Licensee Event Report module; and the Operator Requalification Performance module. Information form these modules can either be used separately or can be combined due to the integrated nature of the system. HFIS has the capability, therefore, to provide insights into those areas of human factors that can reduce the probability of events caused by personnel error at nuclear power plants and promote the health and safety of the public. This information system concept can be applied to other industries as well as the nuclear industry

  3. Genetics of human hydrocephalus (United States)

    Williams, Michael A.; Rigamonti, Daniele


    Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human

  4. Human Power Empirically Explored

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, A.J.


    Harvesting energy from the users' muscular power to convert this into electricity is a relatively unknown way to power consumer products. It nevertheless offers surprising opportunities for product designers; human-powered products function independently from regular power infrastructure, are convenient and can be environmentally and economically beneficial. This work provides insight into the knowledge required to design human-powered energy systems in consumer products from a scientific perspective. It shows the developments of human-powered products from the first introduction of the BayGen Freeplay radio in 1995 till current products and provides an overview and analysis of 211 human-powered products currently on the market. Although human power is generally perceived as beneficial for the environment, this thesis shows that achieving environmental benefit is only feasible when the environmental impact of additional materials in the energy conversion system is well balanced with the energy demands of the products functionality. User testing with existing products showed a preference for speeds in the range of 70 to 190 rpm for crank lengths from 32 to 95 mm. The muscular input power varied from 5 to 21 W. The analysis of twenty graduation projects from the Faculty of Industrial Design Engineering in the field of human-powered products, offers an interesting set of additional practice based design recommendations. The knowledge based approach of human power is very powerful to support the design of human-powered products. There is substantial potential for improvements in the domains energy conversion, ergonomics and environment. This makes that human power, when applied properly, is environmentally and economically competitive over a wider range of applications than thought previously.

  5. Human dignity and bioethics

    Directory of Open Access Journals (Sweden)

    Marjanović Miloš


    Full Text Available By opening the field of bioethics followed a new wave of intense debate on the theological, philosophical and legal significance of the concept of human dignity . Exactly ten years ago (December 2003 American bioethicist Ruth Maclin has proposed to divest ourselves of the concept of human dignity because it is vague, useless and redundant and that, without any loss, we can replace it by the ethical principle of personal autonomy. Her article was followed by harsh reactions and opposite views. What is this term in so broad, almost inflationary and opposite use is not a reason to deprive him, but, on the contrary, it shows how important it is and that it should be determined at least outline. As universal values and general concept, the human dignity has no pre-defined and narrow, precise meaning. It is more an evaluation horizon, the guiding principle and regulatory ideas that must constantly define and codify by many guaranted human rights and fundamental freedoms. As generic notion of each reasonable law, it is their foundation and a common denominator, legitimising basis of natural but also of positive law. As intrinsic and static value which means the humaneness, the humanity it is absolute, inherent to every human being without distinction and conditioning, as a unique and unrepeatable creation. In this meaning, the dignity is the obligation and limitation of the state, society and each of us. As an ethical and dynamic category, it is not given to us, but it is assign to us, and it is not in us, but always before us, as a guide of our actions in accordance with virtues, to treat ourselves, each other and the nature in a human way. The century in which we live is named the century of molecular biology and genetic engineering because of the enormous potential but also risks to human dignity. Because of that human dignity has become a central principle in all international documents relating to the human genome, genetics and bioethics, adopted

  6. Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Block, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Cornwall, J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dally, W. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, F. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Fortson, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Joyce, G. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Kimble, H. J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Lewis, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Max, C. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Prince, T. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, R. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Weinberger, P. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Woodin, W. H. [The MITRE Corporation, McLean, VA (US). JASON Program Office


    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  7. Aluminium in human sweat. (United States)

    Minshall, Clare; Nadal, Jodie; Exley, Christopher


    It is of burgeoning importance that the human body burden of aluminium is understood and is measured. There are surprisingly few data to describe human excretion of systemic aluminium and almost no reliable data which relate to aluminium in sweat. We have measured the aluminium content of sweat in 20 healthy volunteers following mild exercise. The concentration of aluminium ranged from 329 to 5329μg/L. These data equate to a daily excretion of between 234 and 7192μg aluminium and they strongly suggest that perspiration is the major route of excretion of systemic aluminium in humans. Copyright © 2013 Elsevier GmbH. All rights reserved.

  8. Human exposure to aluminium. (United States)

    Exley, Christopher


    Human activities have circumvented the efficient geochemical cycling of aluminium within the lithosphere and therewith opened a door, which was previously only ajar, onto the biotic cycle to instigate and promote the accumulation of aluminium in biota and especially humans. Neither these relatively recent activities nor the entry of aluminium into the living cycle are showing any signs of abating and it is thus now imperative that we understand as fully as possible how humans are exposed to aluminium and the future consequences of a burgeoning exposure and body burden. The aluminium age is upon us and there is now an urgent need to understand how to live safely and effectively with aluminium.

  9. Avian and human metapneumovirus. (United States)

    Broor, Shobha; Bharaj, Preeti


    Pneumovirus infection remains a significant problem for both human and veterinary medicine. Both avian pneumovirus (aMPV, Turkey rhinotracheitis virus) and human metapneumovirus (hMPV) are pathogens of birds and humans, which are associated with respiratory tract infections. Based on their different genomic organization and low level of nucleotide (nt) and amino acid (aa) identity with paramyxoviruses in the genus Pneumovirus, aMPV and hMPV have been classified into a new genus referred to as Metapneumovirus. The advancement of our understanding of pneumovirus biology and pathogenesis of pneumovirus disease in specific natural hosts can provide us with strategies for vaccine formulations and combined antiviral and immunomodulatory therapies.

  10. Refractoriness in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Jespersen, Thomas; Christ, Torsten


    BACKGROUND: Refractoriness of cardiac cells limits maximum frequency of electrical activity and protects the heart from tonic contractions. Short refractory periods support major arrhythmogenic substrates and augmentation of refractoriness is therefore seen as a main mechanism of antiarrhythmic...... drugs. Cardiomyocyte excitability depends on availability of sodium channels, which involves both time- and voltage-dependent recovery from inactivation. This study therefore aims to characterise how sodium channel inactivation affects refractoriness in human atria. METHODS AND RESULTS: Steady......-state activation and inactivation parameters of sodium channels measured in vitro in isolated human atrial cardiomyocytes were used to parameterise a mathematical human atrial cell model. Action potential data were acquired from human atrial trabeculae of patients in either sinus rhythm or chronic atrial...

  11. Human Reliability Program Overview

    Energy Technology Data Exchange (ETDEWEB)

    Bodin, Michael


    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  12. Human Papillomavirus (HPV) Vaccines (United States)

    ... factors for developing them, such as taking oral contraceptives . A safety review of Gardasil in Denmark and ... and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark ...

  13. Human-Machine Communication

    International Nuclear Information System (INIS)

    Farbrot, J.E.; Nihlwing, Ch.; Svengren, H.


    New requirements for enhanced safety and design changes in process systems often leads to a step-wise installation of new information and control equipment in the control room of older nuclear power plants, where nowadays modern digital I and C solutions with screen-based human-machine interfaces (HMI) most often are introduced. Human factors (HF) expertise is then required to assist in specifying a unified, integrated HMI, where the entire integration of information is addressed to ensure an optimal and effective interplay between human (operators) and machine (process). Following a controlled design process is the best insurance for ending up with good solutions. This paper addresses the approach taken when introducing modern human-machine communication in the Oskarshamn 1 NPP, the results, and the lessons learned from this work with high operator involvement seen from an HF point of view. Examples of possibilities modern technology might offer for the operators are also addressed. (orig.)

  14. Human Bond Communication

    DEFF Research Database (Denmark)

    Prasad, Ramjee


    Modern dexterous communication technology is progressively enabling humans to communicate their information through them with speech (aural) and media (optical) as underpinning essence. Humans realize this kind of aural and optical information by their optical and auditory senses. However, due...... to certain constraints, the ability to incorporate the other three sensory features namely, olfactory, gustatory, and tactile are still far from reality. Human bond communication is a novel concept that incorporates olfactory, gustatory, and tactile that will allow more expressive and holistic sensory...... information exchange through communication techniques for more human sentiment centric communication. This concept endorses the need of inclusion of other three senses and proposes an innovative approach of holistic communication for future communication network....

  15. OAS :: Accountability :: Human Resources (United States)

    OAS, including its organizational structure, each organizational unit's staffing, vacant posts, and a list of procurement notices for formal bids, links to the performance contract and travel control Plan Human Resources Organizational Structure Functions of each organizational unit Vacant Posts

  16. Spaceflight Versus Human Spaceflight (United States)

    Barr, Stephanie


    Spaceflight is challenging. Human spaceflight is far more challenging,.Those familiar with spaceflight recognize that human spaceflight is more than tacking an environmental control system on an existing spacecraft, that there are a number of serious technical challenges involved in sending people out into space and bringing them back home safely.The return trip, bringing the crew back to the surface of the earth safely, is more than just an additional task, it's the new imperative. Differences between manned and unmanned spaceflight are more than technical. The human element forces a change in philosophy, a mindset that will likely touch every aspect of flight from launch through mission and return. Seasoned space professionals used to the paradigms and priorities of unmanned flight need to be cognizant of these differences and some of the implications, perhaps most especially because mission success and human safety priorities are sometimes contradictory.

  17. Calvin and human dignity

    Directory of Open Access Journals (Sweden)

    J.M. Vorster


    Full Text Available Human dignity has become a major moral directive in the contemporary ethical reflection on human rights and bio-ethics. This article examines the theological foundations laid by the reformer Calvin regarding the inherent dignity of people, and his influence on post-World War ethical reflection about the violations of human rights. In this article his views on the “imago dei” and common grace, the “lex naturae” and the obligations of the civil authority are investigated in order to illuminate his ideas about the dignity of human beings. The article then deals with the influence of these ideas in the influential works of the twentieth century’s reformed theologians Barth, Berkhouwer and Moltmann.

  18. Designing Human Technologies

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    and the design process, in ethical and society-related concerns, and in evaluating how designs fulfill needs and solve problems. Designing Human Technologies subscribes to a broad technology concept including information and communication, mobile, environmental/sustainable and energy technologies......Design is increasingly becoming a part of the university curriculum and research agenda. The keynote present and discuss Designing Human Technologies – an initiative aiming at establishing a design oriented main subject area alongside traditional main subject areas such as Natural Science......, the Humanities, and Social Science. The initiative broadens the perspective of IS and recognize reflections on aesthetics, ethics, values, connections to politics, and strategies for enabling a better future as legitimate parts of the research agenda. Designing Human Technologies is a design-oriented Strategic...

  19. Visible Human Project (United States)

    ... cryosections are associated with anatomical terminology. AnatLine : A prototype system consisting of an anatomical image database and ... further information is available Publications VHJOE: Visible Human Journal of Endoscopy. NLM's Current Bibliographies in Medicine, Visible ...


    Directory of Open Access Journals (Sweden)

    Željko Kaluđerović


    Full Text Available In this paper the authors analyze the process of negotiating and beginning of the United Nations Declaration on Human Cloning as well as the paragraphs of the very Declaration. The negotiation was originally conceived as a clear bioethical debate that should have led to a general agreement to ban human cloning. However, more often it had been discussed about human rights, cultural, civil and religious differences between people and about priorities in case of eventual conflicts between different value systems. In the end, a non-binding Declaration on Human Cloning had been adopted, full of numerous compromises and ambiguous formulations, that relativized the original intention of proposer states. According to authors, it would have been better if bioethical discussion and eventual regulations on cloning mentioned in the following text had been left over to certain professional bodies, and only after the public had been fully informed about it should relevant supranational organizations have taken that into consideration.

  1. Human Research Program (United States)

    National Aeronautics and Space Administration — Strategically, the HRP conducts research and technology development that: 1) enables the development or modification of Agency-level human health and performance...

  2. Bridging Humanism and Behaviorism. (United States)

    Chu, Lily


    Humanistic behaviorism may provide the necessary bridge between behaviorism and humanism. Perhaps the most humanistic approach to teaching is to learn how certain changes will help students and how these changes can be accomplished. (Author/MLF)

  3. Humanism vs. Behaviorism (United States)

    Hunter, Madeline


    Author argues that humanism and behaviorism are not necessarily exclusive of one another, and that principles of behaviorism, when thoughtfully applied, can lead to the achievement of humanistic goals. (RW)

  4. Human factors in aviation

    National Research Council Canada - National Science Library

    Salas, Eduardo; Maurino, Daniel E


    .... HFA offers a comprehensive overview of the topic, taking readers from the general to the specific, first covering broad issues, then the more specific topics of pilot performance, human factors...

  5. Human Capital Tracking Tool - (United States)

    Department of Transportation — AVS is now required to collect, track, and report on data from the following Flight, Business and Workforce Plan. The Human Resource Management’s Performance Target...

  6. Human Factors Laboratory (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  7. Evaluating human genetic diversity

    National Research Council Canada - National Science Library

    ... into human evolution and origins and serving as a springboard for important medical research. It also addresses issues of confidentiality and individual privacy for participants in genetic diversity research studies.

  8. Biotechnology and human rights. (United States)

    Feuillet-Le Mintier, B


    Biotechnology permits our world to progress. It's a tool to better apprehend the human being, but as well to let him go ahead. Applied to the living, biotechnologies present the same finality. But since their matter concerns effectively the living, they are the sources of specific dangers and particularly of that one to use the improvements obtained on the human to modify the human species. The right of the persons has to find its place to avoid that the fundamental rights of the human personality shall undergo harm. This mission assigned to the right of the persons is as so much invaluable that the economical stakes are particularly important in the domain of the biotechnologies.

  9. Human-Robot Teams Informed by Human Performance Moderator Functions (United States)


    performance factors that affect the ability of a human to drive at night, which includes the eyesight of the driver, the fatigue level of the driver...where human factors are factors that affect the performance of an individual. 7 for human interaction. For instance, they explain the various human... affecting trust in human-robot interaction. Human Factors 53(5), 517-527 (2001) 35. Hart, S. G. and Staveland, L. E. Development of NASA-TLX (Task

  10. Human Assisted Assembly Processes

    Energy Technology Data Exchange (ETDEWEB)



    Automatic assembly sequencing and visualization tools are valuable in determining the best assembly sequences, but without Human Factors and Figure Models (HFFMs) it is difficult to evaluate or visualize human interaction. In industry, accelerating technological advances and shorter market windows have forced companies to turn to an agile manufacturing paradigm. This trend has promoted computerized automation of product design and manufacturing processes, such as automated assembly planning. However, all automated assembly planning software tools assume that the individual components fly into their assembled configuration and generate what appear to be a perfectly valid operations, but in reality the operations cannot physically be carried out by a human. Similarly, human figure modeling algorithms may indicate that assembly operations are not feasible and consequently force design modifications; however, if they had the capability to quickly generate alternative assembly sequences, they might have identified a feasible solution. To solve this problem HFFMs must be integrated with automated assembly planning to allow engineers to verify that assembly operations are possible and to see ways to make the designs even better. Factories will very likely put humans and robots together in cooperative environments to meet the demands for customized products, for purposes including robotic and automated assembly. For robots to work harmoniously within an integrated environment with humans the robots must have cooperative operational skills. For example, in a human only environment, humans may tolerate collisions with one another if they did not cause much pain. This level of tolerance may or may not apply to robot-human environments. Humans expect that robots will be able to operate and navigate in their environments without collisions or interference. The ability to accomplish this is linked to the sensing capabilities available. Current work in the field of cooperative

  11. Pushing Human Frontiers (United States)

    Zubrin, Robert


    With human colonization of Mars, I think you will see a higher standard of civilization, just as America set a higher standard of civilization which then promulgated back into Europe. I think that if you want to maximize human potential, you need a higher standard of civilization, and that becomes an example that benefits everyone. Without an open frontier, closed world ideologies, such as the Malthus Theory, tend to come to the forefront. It is that there are limited resources; therefore, we are all in deadly competition with each other for the limited pot. The result is tyrannical and potentially genocidal regimes, and we've already seen this in the twentieth century. There s no truth in the Malthus Theory, because human beings are the creators of their resources. With every mouth comes a pair of hands and a brain. But if it seems to be true, you have a vector in this direction, and it is extremely unfortunate. It is only in a universe of infinite resources that all humans can be brothers and sisters. The fundamental question which affects humanity s sense of itself is whether the world is changeable or fixed. Are we the makers of our world or just its inhabitants? Some people have a view that they re living at the end of history within a world that s already defined, and there is no fundamental purpose to human life because there is nothing humans can do that matters. On the other hand, if humans understand their own role as the creators of their world, that s a much more healthy point of view. It raises the dignity of humans. Indeed, if we do establish a new branch of human civilization on Mars that grows in time and potency to the point where it cannot really settle Mars, but transforms Mars, and brings life to Mars, we will prove to everyone and for all time the precious and positive nature of the human species and every member of it.

  12. Business and Human Rights

    DEFF Research Database (Denmark)

    Buhmann, Karin


    This article analyses the United Nations (UN) Guidelines on Business and Human Rights adopted in 2011 by the UN Human Rights Council from the perspective of transnational business governance interactions (TBGI) analytical framework.1 The article identifies and discusses dimensions of interaction...... in several areas of relevance to transnational business governance interaction and indicates the relevance of the TBGI approach to public regulatory transnational business governance initiatives. The analysis of the Guiding Principles as interactional transnational business governance suggests that this form...

  13. Quality and human society (United States)

    Stoll, W.


    Quality of products and services is seen as a necessity in our modern world. Quality also has important cross-links to safety in our society. It is however suggested, that human beings are living in their industrial environment under the stress of a fractured personality with anxieties and frustrations. Some cultural comparisons with other industrial nations are given. Quality control tailored to human nature is recommended.

  14. Human ocular anatomy. (United States)

    Kels, Barry D; Grzybowski, Andrzej; Grant-Kels, Jane M


    We review the normal anatomy of the human globe, eyelids, and lacrimal system. This contribution explores both the form and function of numerous anatomic features of the human ocular system, which are vital to a comprehensive understanding of the pathophysiology of many oculocutaneous diseases. The review concludes with a reference glossary of selective ophthalmologic terms that are relevant to a thorough understanding of many oculocutaneous disease processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Human Germline Genome Editing. (United States)

    Ormond, Kelly E; Mortlock, Douglas P; Scholes, Derek T; Bombard, Yvonne; Brody, Lawrence C; Faucett, W Andrew; Garrison, Nanibaa' A; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E


    With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counselors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counselors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The statement includes the following positions. (1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy. (2) Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research. (3) Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input. Copyright © 2017 American Society of Human Genetics. All rights reserved.

  16. Cytokines in human milk. (United States)

    Garofalo, Roberto


    Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system. Copyright 2010. Published by Mosby, Inc.

  17. Human Performance Evaluation System

    International Nuclear Information System (INIS)

    Hardwick, R.J. Jr.


    Operating nuclear power plants requires high standards of performance, extensive training and responsive management. Despite our best efforts inappropriate human actions do occur, but they can be managed. An extensive review of License Event Reports (LERs) was conducted which indicated continual inadequacy in human performance and in evaluation of root causes. Of some 31,000 LERs, about 5,000 or 16% were directly attributable to inappropriate actions. A recent analysis of 87 Significant Event Reports (issued by INPO in 1983) identified inappropriate actions as being the most frequent root cause (44% of the total). A more recent analysis of SERs issued in 1983 and 1984 indicate that 52% of the root causes were attributed to human performance. The Human Performance Evaluation System (HPES) is a comprehensive, coordinated utility/industry system for evaluating and reporting human performance situtations. HPES is a result of the realization that current reporting system provide limited treatment of human performance and rarely provide adequate information about root causes of inappropriate actions by individuals. The HPES was implemented to identify and eliminate root causes of inappropriate actions

  18. Human Factors Review Plan

    International Nuclear Information System (INIS)

    Paramore, B.; Peterson, L.R.


    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management

  19. Human Factors Review Plan

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, B.; Peterson, L.R. (eds.)


    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.


    Directory of Open Access Journals (Sweden)

    David Abram


    Full Text Available From an initial project to investigate the relationship between magic and traditional medicine as practiced by shamans in Southern rural Asia, the focus of attention gradually shifted to an awareness of the negotiation traditional medicine people or shamans exert between the human community and the larger community of beings. This attentiveness to a more-than-human world does not occur at a supernatural domain above nature or inside her personal self but is the result of the shaman’s special ability to project her consciousness horizontally to other forms of sensibility with which human existence is interwoven. The ecological function of the shaman is to maintain a constant balance between what is taken and what is given from the human community to the larger community. The spirits of indigenous cultures are not defined in opposition to materiality but are essentially those modes of intelligence or awareness that do not possess a human form. By exploring different landscapes, and the sensibility living in them, a new sensitivity is awoken that allows for communication with those intelligences. However, the drowning of these other voices in Western culture, which reduces otherness to an object, creates an uneasiness that is hardly perceived except as an inability to interact with anything more-than-human and its dire consequences in the form of “civilization’s” destructive behavior.

  1. Deuteronomy and Human Rights

    Directory of Open Access Journals (Sweden)

    G. Braulik


    Full Text Available If one compares the articles of the "Universal Declaration of Human Rights" dated December 10th, 1948, with the regulations of the book of Deuteronomy, one detects a surprising abundance of correspondences, or at least of similar tendencies, between them. As the social theorists of the seventeenth and eighteenth centuries, the architects of the catalogue of Human Rights, knew the Scripture very well. References to Deuteronomy are historically well probable and factually hardly coincidental. Deuteronomy rightly boasts about its social laws (4:8 that are unique in the Ancient Near East. The paper orientates itself to the short formula of Human Rights and at the same time to the normative basic character of each human right, as it is formulated in the first article of the declaration: "liberty", "equality", "fraternity". Each of these basic categories are concretised in terms of several Deuteronomic regulations and prove themselves to be central matters of concern within the YHWH religion. Finally, it is outlined how the connection between Deuteronomy and modem expressions of human rights might be explained, and further it is shown what actually makes up the peculiarity of biblical thinking on human rights.

  2. Habitability and Human Factors Contributions to Human Space Flight (United States)

    Sumaya, Jennifer Boyer


    This slide presentation reviews the work of the Habitability and Human Factors Branch in support of human space flight in two main areas: Applied support to major space programs, and Space research. The field of Human Factors applies knowledge of human characteristics for the design of safer, more effective, and more efficient systems. This work is in several areas of the human space program: (1) Human-System Integration (HSI), (2) Orion Crew Exploration Vehicle, (3) Extravehicular Activity (EVA), (4) Lunar Surface Systems, (5) International Space Station (ISS), and (6) Human Research Program (HRP). After detailing the work done in these areas, the facilities that are available for human factors work are shown.

  3. Human bites - self-care (United States)

    Bites - human - self-care ... Human bites can occur in 2 ways: If someone bites you If your hand comes into contact ... bite to express anger or other negative feelings. Human bites may be more dangerous than animal bites. ...

  4. Tabhu: tools for antibody humanization.

    KAUST Repository

    Olimpieri, Pier Paolo; Marcatili, Paolo; Tramontano, Anna


    for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps of the humanization experiment protocol. AVAILABILITY: http

  5. Human dignity, humiliation, and torture. (United States)

    Luban, David


    Modern human rights instruments ground human rights in the concept of human dignity, without providing an underlying theory of human dignity. This paper examines the central importance of human dignity, understood as not humiliating people, in traditional Jewish ethics. It employs this conception of human dignity to examine and criticize U.S. use of humiliation tactics and torture in the interrogation of terrorism suspects.

  6. Towards a better understanding of human smuggling


    Heckmann, Friedrich


    Contents: What is human smuggling?; How can we know about human smuggling?; Human smuggling as a migration phenomenon; Human smuggling as a business; The social organizing of human smuggling; Fighting against human smuggling.

  7. Why Geo-Humanities (United States)

    Graells, Robert Casals i.; Sibilla, Anna; Bohle, Martin


    Anthropogenic global change is a composite process. It consists of societal processes (in the 'noosphere') and natural processes (in the 'bio-geosphere'). The 'noosphere' is the ensemble of social, cultural or political insights ('shared subjective mental concepts') of people. Understanding the composite of societal and natural processes ('human geo-biosphere intersections'), which shapes the features of anthropogenic global change, would benefit from a description that draws equally on natural sciences, social sciences and humanities. To that end it is suggested to develop a concept of 'geo-humanities': This essay presents some aspects of its scope, discussing "knowledge that is to manage", "intentions that are to shape", "choices that are to justify" and "complexity that is to handle". Managing knowledge: That people understand anthropogenic global change requires their insights into how 'human geosphere intersections' function. Insights are formed ('processed') in the noosphere by means of interactions between people. Understanding how 'human geosphere intersections' functions combines scientific, engineering and economic studies with studies of the dynamics of the noosphere. Shaping intentions: During the last century anthropogenic global change developed as the collateral outcome of humankind's accumulated actions. It is caused by the number of people, the patterns of their consumption of resources, and the alterations of their environments. Nowadays, anthropogenic global chance is either an intentional negligence or a conscious act. Justifying choices: Humanity has alternatives how to alter Earth at planetary scale consciously. For example, there is a choice to alter the geo-biosphere or to adjust the noosphere. Whatever the choice, it will depend on people's world-views, cultures and preferences. Thus beyond issues whether science and technology are 'sound' overarching societal issues are to tackle, such as: (i) how to appropriate and distribute natural

  8. The Human Serum Metabolome (United States)

    Psychogios, Nikolaos; Hau, David D.; Peng, Jun; Guo, An Chi; Mandal, Rupasri; Bouatra, Souhaila; Sinelnikov, Igor; Krishnamurthy, Ramanarayan; Eisner, Roman; Gautam, Bijaya; Young, Nelson; Xia, Jianguo; Knox, Craig; Dong, Edison; Huang, Paul; Hollander, Zsuzsanna; Pedersen, Theresa L.; Smith, Steven R.; Bamforth, Fiona; Greiner, Russ; McManus, Bruce; Newman, John W.; Goodfriend, Theodore; Wishart, David S.


    Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology) in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at PMID:21359215

  9. Human Performance Event Database

    International Nuclear Information System (INIS)

    Trager, E. A.


    The purpose of this paper is to describe several aspects of a Human Performance Event Database (HPED) that is being developed by the Nuclear Regulatory Commission. These include the background, the database structure and basis for the structure, the process for coding and entering event records, the results of preliminary analyses of information in the database, and plans for the future. In 1992, the Office for Analysis and Evaluation of Operational Data (AEOD) within the NRC decided to develop a database for information on human performance during operating events. The database was needed to help classify and categorize the information to help feedback operating experience information to licensees and others. An NRC interoffice working group prepared a list of human performance information that should be reported for events and the list was based on the Human Performance Investigation Process (HPIP) that had been developed by the NRC as an aid in investigating events. The structure of the HPED was based on that list. The HPED currently includes data on events described in augmented inspection team (AIT) and incident investigation team (IIT) reports from 1990 through 1996, AEOD human performance studies from 1990 through 1993, recent NRR special team inspections, and licensee event reports (LERs) that were prepared for the events. (author)

  10. Humanity and Sustainability

    Directory of Open Access Journals (Sweden)

    Shu-Kun Lin


    Full Text Available So far our open access publishing company MDPI (Multidisciplinary Digital Publishing Institute has published mainly science, medicine and technology journals. To become a multidisciplinary publisher, we launched the journal Sustainability [1]. More recently, we started to run several social science journals, including Societies [2], Religions [3], Administrative Sciences [4] and Behavioral Sciences [5]. Today we published the first paper [6] of the inaugural issue of Humanities (ISSN 2076-0787. This will be an international open access journal, publishing scholarly papers of high quality across all humanities disciplines. As a publisher, I would like to publish journals surrounding the topics of sustainability and I believe the humanities as a discipline of academic studies are very important. As a scientist, I believed science and technology will only benefit human beings. I was raised in a small village, living a very primitive life in a peasant family: no electricity, no machines, of course no TV and no refrigerator. Now, the life of my children is completely different. Even my own life has completely changed. I have witnessed very rapid changes: more and more machines are used to consume mineral resources and energy and to pollute the environment, in order to produce more and more powerful machines (we are also launching a journal titled Machines, in which the relationship between Man and machine should be an interesting topic.. Machines are more and more like human individuals consuming resources themselves (we are launching a journal titled Resources. [...

  11. Healthy human gut phageome. (United States)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T; van der Oost, John; de Vos, Willem M; Young, Mark J


    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health.

  12. Human hybrid hybridoma

    Energy Technology Data Exchange (ETDEWEB)

    Tiebout, R.F.; van Boxtel-Oosterhof, F.; Stricker, E.A.M.; Zeijlemaker, W.P.


    Hybrid hybridomas are obtained by fusion of two cells, each producing its own antibody. Several authors have reported the construction of murine hybrid hybridomas with the aim to obtain bispecific monoclonal antibodies. The authors have investigated, in a model system, the feasibility of constructing a human hybrid hybridoma. They fused two monoclonal cell lines: an ouabain-sensitive and azaserine/hypoxanthine-resistant Epstein-Barr virus-transformed human cell line that produces an IgG1kappa antibody directed against tetanus toxiod and an azaserine/hypoxanthine-sensitive and ouabain-resistant human-mouse xenohybrid cell line that produces a human IgG1lambda antibody directed against hepatitis-B surface antigen. Hybrid hybridoma cells were selected in culture medium containing azaserine/hypoxanthine and ouabain. The hybrid nature of the secreted antibodies was analyzed by means of two antigen-specific immunoassay. The results show that it is possible, with the combined use of transformation and xenohybridization techniques, to construct human hybrid hybridomas that produce bispecific antibodies. Bispecific antibodies activity was measured by means of two radioimmunoassays.

  13. Philosophical foundations of human rights

    CERN Document Server

    Liao, Matthew S


    What makes something a human right? What is the relationship between the moral foundations of human rights and human rights law? What are the difficulties of appealing to human rights? This book offers the first comprehensive survey of current thinking on the philosophical foundations of human rights. Divided into four parts, this book focusses firstly on the moral grounds of human rights, for example in our dignity, agency, interests or needs. 'Secondly, it looks at the implications that different moral perspectives on human rights bear for human rights law and politics. Thirdly, it discusses specific and topical human rights including freedom of expression and religion, security, health and more controversial rights such as a human right to subsistence. The final part discusses nuanced critical and reformative views on human rights from feminist, Kantian and relativist perspectives among others. The essays represent new and canonical research by leading scholars in the field. Each part is comprised of a set...

  14. Movement coordination in applied human-human and human-robot interaction

    DEFF Research Database (Denmark)

    Schubö, Anna; Vesper, Cordula; Wiesbeck, Mathey


    and describing human-human interaction in terms of goal-oriented movement coordination is considered an important and necessary step for designing and describing human-robot interaction. In the present scenario, trajectories of hand and finger movements were recorded while two human participants performed......The present paper describes a scenario for examining mechanisms of movement coordination in humans and robots. It is assumed that coordination can best be achieved when behavioral rules that shape movement execution in humans are also considered for human-robot interaction. Investigating...... coordination were affected. Implications for human-robot interaction are discussed....


    Directory of Open Access Journals (Sweden)

    Suzana Miovska Spaseva


    Full Text Available The article examines the complex role and great responsibility of the education today in development of the moral strength and human values of the children and youth. At the beginning of the article the author reconsiders the pedagogical ideas of Maria Montessori and her concept of education for peace as an instrument for reconstruction of the society and for improvement of the human living. Than the analysis of the moral values in the contemporary society is made and several issues and dilemmas are discussed referring the value disorientation of the youth and the importance of the models of adult’s moral behavior in their search for personal identity. On the basis of this analysis, the human dimension of the education is elaborated enhancing the need for its understanding as support of development, which is based on several crucial elements: love, freedom and spirit of community.

  16. Seaweed and human health. (United States)

    Brown, Emma S; Allsopp, Philip J; Magee, Pamela J; Gill, Chris I R; Nitecki, Sonja; Strain, Conall R; McSorley, Emeir M


    Seaweeds may have an important role in modulating chronic disease. Rich in unique bioactive compounds not present in terrestrial food sources, including different proteins (lectins, phycobiliproteins, peptides, and amino acids), polyphenols, and polysaccharides, seaweeds are a novel source of compounds with potential to be exploited in human health applications. Purported benefits include antiviral, anticancer, and anticoagulant properties as well as the ability to modulate gut health and risk factors for obesity and diabetes. Though the majority of studies have been performed in cell and animal models, there is evidence of the beneficial effect of seaweed and seaweed components on markers of human health and disease status. This review is the first to critically evaluate these human studies, aiming to draw attention to gaps in current knowledge, which will aid the planning and implementation of future studies.

  17. Human Environmental Disease Network

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Audouze, Karine


    During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...... and their disease relationships from the reported TDDB database. The resulting human EDN takes into consideration the level of evidence of the toxicant-disease relationships allowing including some degrees of significance in the disease-disease associations. Such network can be used to identify uncharacterized...

  18. Human Systems Design Criteria

    DEFF Research Database (Denmark)

    Rasmussen, Jens


    This paper deals with the problem of designing more humanised computer systems. This problem can be formally described as the need for defining human design criteria, which — if used in the design process - will secure that the systems designed get the relevant qualities. That is not only...... the necessary functional qualities but also the needed human qualities. The author's main argument is, that the design process should be a dialectical synthesis of the two points of view: Man as a System Component, and System as Man's Environment. Based on a man's presentation of the state of the art a set...... of design criteria is suggested and their relevance discussed. The point is to focus on the operator rather than on the computer. The crucial question is not to program the computer to work on its own conditions, but to “program” the operator to function on human conditions....

  19. Defining Human Enhancement

    DEFF Research Database (Denmark)

    Nordberg, Ana


    -matter definitions are vital legal tools to determine what is currently regulated in established fields of law and whether there is room for a new legal field – Enhancement Law. This paper provides a reflection on the relevance of establishing a legal definition of human enhancement and to what extent different...... legal fields and jurisdictions may warrant different understandings of such concept. It reviews a number of different and often divergent concepts and taxonomies of human enhancement and concludes with the proposal and analysis of a definition: Use of technological means with the intention to improve......Emerging technologies open the prospect of extraordinary interventions on the human body. These may go beyond what is strictly necessary to sustain health and well-being. While responding to social and ethical challenges of such advances, the Law simultaneously faces the challenge of reflecting...

  20. Human factors guides

    International Nuclear Information System (INIS)

    Penington, J.


    This document presents human factors guides, which have been developed in order to provide licensees of the AECB with advice as to how to address human factors issues within the design and assessment process. This documents presents the results of a three part study undertaken to develop three guides which are enclosed in this document as Parts B, C and D. As part of the study human factors standards, guidelines, handbooks and other texts were researched, to define those which would be most useful to the users of the guides and for the production of the guides themselves. Detailed specifications were then produced to outline the proposed contents and format of the three guides. (author). 100 refs., 3 tabs., 11 figs

  1. Human factors guides

    Energy Technology Data Exchange (ETDEWEB)

    Penington, J [PHF Services Inc., (Canada)


    This document presents human factors guides, which have been developed in order to provide licensees of the AECB with advice as to how to address human factors issues within the design and assessment process. This documents presents the results of a three part study undertaken to develop three guides which are enclosed in this document as Parts B, C and D. As part of the study human factors standards, guidelines, handbooks and other texts were researched, to define those which would be most useful to the users of the guides and for the production of the guides themselves. Detailed specifications were then produced to outline the proposed contents and format of the three guides. (author). 100 refs., 3 tabs., 11 figs.

  2. Human-Robot Interaction (United States)

    Rochlis-Zumbado, Jennifer; Sandor, Aniko; Ezer, Neta


    Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI) is a new Human Research Program (HRP) risk. HRI is a research area that seeks to understand the complex relationship among variables that affect the way humans and robots work together to accomplish goals. The DRP addresses three major HRI study areas that will provide appropriate information for navigation guidance to a teleoperator of a robot system, and contribute to the closure of currently identified HRP gaps: (1) Overlays -- Use of overlays for teleoperation to augment the information available on the video feed (2) Camera views -- Type and arrangement of camera views for better task performance and awareness of surroundings (3) Command modalities -- Development of gesture and voice command vocabularies

  3. Models of human operators

    International Nuclear Information System (INIS)

    Knee, H.E.; Schryver, J.C.


    Models of human behavior and cognition (HB and C) are necessary for understanding the total response of complex systems. Many such models have come available over the past thirty years for various applications. Unfortunately, many potential model users remain skeptical about their practicality, acceptability, and usefulness. Such hesitancy stems in part to disbelief in the ability to model complex cognitive processes, and a belief that relevant human behavior can be adequately accounted for through the use of commonsense heuristics. This paper will highlight several models of HB and C and identify existing and potential applications in attempt to dispel such notions. (author)

  4. On human health. (United States)

    van Spijk, Piet


    If it is true that health is a priority objective of medicine, then medical practice can only be successful if the meaning of the term "health" is known. Various attempts have been made over the years to define health. This paper proposes a new definition. In addition to current health concepts, it also takes into account the distinction between specifically human (great) health and health as the absence of disease and illness-i.e. small health. The feeling of leading a life that makes sense plays a key role in determining specifically human great health.

  5. Human cryptosporidiosis: a review. (United States)

    Ayuo, P O


    To provide an overview of risk factors, presentation and management of human cryptosporidium infection. Literature review was obtained through PubMed search. Published articles on the taxonomy of Cryptosporidium and the epidemiology, clinical presentation and management of cryptosporidiosis were reviewed. Abstracts and complete articles relevant to the objective were selected, read and analysed to extract information for this article. Human cryptosporidiosis is a severe diarrhoeal disease in malnourished children and immuno-compromised adults in whom it confers poor prognosis. Management is mainly supportive as drug therapy remains elusive. Fortunately the prevalence in AIDS patients is declining due to the widespread use of combination antiretroviral therapy (cART).

  6. When computers were human

    CERN Document Server

    Grier, David Alan


    Before Palm Pilots and iPods, PCs and laptops, the term ""computer"" referred to the people who did scientific calculations by hand. These workers were neither calculating geniuses nor idiot savants but knowledgeable people who, in other circumstances, might have become scientists in their own right. When Computers Were Human represents the first in-depth account of this little-known, 200-year epoch in the history of science and technology. Beginning with the story of his own grandmother, who was trained as a human computer, David Alan Grier provides a poignant introduction to the wider wo

  7. Human push capability. (United States)

    Barnett, Ralph L; Liber, Theodore


    Use of unassisted human push capability arises from time to time in the areas of crowd and animal control, the security of locked doors, the integrity of railings, the removal of tree stumps and entrenched vehicles, the manoeuvering of furniture, and athletic pursuits such as US football or wrestling. Depending on the scenario, human push capability involves strength, weight, weight distribution, push angle, footwear/floor friction, and the friction between the upper body and the pushed object. Simple models are used to establish the relationships among these factors.

  8. Ayahuasca and human destiny. (United States)

    McKenna, Dennis J


    In this essay, the author shares his personal reflections gleaned from a lifetime of research with ayahuasca, and speculates on the societal, political, planetary, and evolutionary implications of humanity's aeons-old symbiosis with this shamanic plant. The thesis is developed that at this critical historical juncture, ayahuasca has developed a strategy to broadcast its message to a wider world--a reflection of the urgent need to avert global ecological catastrophe. While ayahuasca has much to teach us, the critical question is, will humanity hear it, and heed it, in time?

  9. Business and Human Rights

    DEFF Research Database (Denmark)

    Buhmann, Karin

    This article analyses the United Nations (UN) Guidelines on Business and Human Rights adopted in 2011 by the UN Human Rights Council from the perspective of Transnational Business Governance Interactions (TBGI) analytical framework (Eberlein et al. 2014). The article identifies and discusses...... that the UN Guiding Principles are unique in several respects of relevance to transnational business governance interaction and indicate the relevance of the TBGI approach to public regulatory transnational business governance initiatives. The analysis of the Guiding Principles as interactional transnational...... business governance suggests that this form of governance offers prospects for public institutions as a means towards regulating global sustainability concerns....

  10. The human myotendinous junction

    DEFF Research Database (Denmark)

    Knudsen, A B; Larsen, M; Mackey, Abigail


    The myotendinous junction (MTJ) is a specialized structure in the musculotendinous system, where force is transmitted from muscle to tendon. Animal models have shown that the MTJ takes form of tendon finger-like processes merging with muscle tissue. The human MTJ is largely unknown and has never...... been described in three dimensions (3D). The aim of this study was to describe the ultrastructure of the human MTJ and render 3D reconstructions. Fourteen subjects (age 25 ± 3 years) with isolated injury of the anterior cruciate ligament (ACL), scheduled for reconstruction with a semitendinosus...

  11. Human Body Exergy Metabolism


    Mady, Carlos Eduardo Keutenedjian


    The exergy analysis of the human body is a tool that can provide indicators of health and life quality. To perform the exergy balance it is necessary to calculate the metabolism on an exergy basis, or metabolic exergy, although there is not yet consensus in its calculation procedure. Hence, the aim of this work is to provide a general method to evaluate this physical quantity for human body based on indirect calorimetry data. To calculate the metabolism on an exergy basis it is necessary to d...

  12. Nature of Human Rights

    Directory of Open Access Journals (Sweden)

    Carlos López Dawson


    Full Text Available In the formation of a new Constitution the constituents will require to know or reach an agreement on the nature of human rights; then, to determine how the State will enforce the respect to those rights. To do so, it is necessary to resort to the history and evolution of these rights, and the present work aims to contribute to an efficient productive debate about the nature of human rights, so that citizens can decide on the understanding that this is a thoughtful democratic and humanistic founded decision. The analysis is in the actual technical-ideological republican system which correspond to the current state of international law

  13. Post-human Viewing

    DEFF Research Database (Denmark)

    Blaagaard, Bolette


    to become part of a global cultural flow, thus calling into question the physical connection between viewer and image. This article analyses what happens to that connection when not only the image but also the physical body is mediated and challenged in post-human relations, and examines the ensuing ethical...... implications. The author takes photojournalism and, in particular, mobile phone footage as a starting point for an exploration of the (post-human) body as evidence and sign of authenticity in the modern age of digital communications and journalism....

  14. Business and Human Rights

    DEFF Research Database (Denmark)

    Buhmann, Karin


    This article analyses the United Nations (UN) Guidelines on Business and Human Rights adopted in 2011 by the UN Human Rights Council from the perspective of transnational business governance interactions (TBGI) analytical framework.1 The article identifies and discusses dimensions of interaction...... and components of regulatory governance which characterize the Guiding Principles, focusing in particular on rule formation and implementation. The article notes that the Guiding Principles actively enrolled other actors for the rule-making process, ensuring support in a politically and legally volatile field...

  15. Handbook of human computation

    CERN Document Server

    Michelucci, Pietro


    This volume addresses the emerging area of human computation, The chapters, written by leading international researchers, explore existing and future opportunities to combine the respective strengths of both humans and machines in order to create powerful problem-solving capabilities. The book bridges scientific communities, capturing and integrating the unique perspective and achievements of each. It coalesces contributions from industry and across related disciplines in order to motivate, define, and anticipate the future of this exciting new frontier in science and cultural evolution. Reade

  16. The Humanities, Human Rights, and the Comparative Imagination


    McClennen, Sophia A.


    In her paper "The Humanities, Human Rights, and the Comparative Imagination" Sophia A. McClennen argues that understanding the relationship between culture and human rights depends on humanist perspectives attentive to the relationship between storytelling and identity, mass culture and ideology, text and audience, critical thinking and engaged citizenship. After briefly considering how the divide between the humanities and human rights advocates developed and how it might best be overcome, s...

  17. Human Modeling for Ground Processing Human Factors Engineering Analysis (United States)

    Stambolian, Damon B.; Lawrence, Brad A.; Stelges, Katrine S.; Steady, Marie-Jeanne O.; Ridgwell, Lora C.; Mills, Robert E.; Henderson, Gena; Tran, Donald; Barth, Tim


    There have been many advancements and accomplishments over the last few years using human modeling for human factors engineering analysis for design of spacecraft. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the human modeling currently used at Kennedy Space Center (KSC), and to explain the future plans for human modeling for future spacecraft designs

  18. Human Dignity – Constitutional Principle of Fundamental Human Rights

    Directory of Open Access Journals (Sweden)

    Lucian Pop


    Full Text Available As a constitutional principle of the human rights, the human dignity is a supreme value, a norm and a right, thus that the reconfiguration of protection standards of fundamental human rights is made by cohesion of the legal, social and moral dimensions of human dignity. With this article, the author argues that legal meaning, social meaning and moral meaning of human dignity, are centerpiece of protection of freedom under law.

  19. The Case for the Humanities. (United States)

    Cary, Michael S.


    Describes the current impoverishment of the humanities and the gulf separating the humanities from the sciences. Discusses the need for adequate humanities instruction at the elementary-secondary level. Suggests that humanities teachers rediscover the Italian Renaissance spirit to improve their teaching. (SB)

  20. Making IBM's Computer, Watson, Human (United States)

    Rachlin, Howard


    This essay uses the recent victory of an IBM computer (Watson) in the TV game, "Jeopardy," to speculate on the abilities Watson would need, in addition to those it has, to be human. The essay's basic premise is that to be human is to behave as humans behave and to function in society as humans function. Alternatives to this premise are considered…