WorldWideScience

Sample records for essential functional replacement

  1. Essential Specification Elements for Heat Exchanger Replacement

    Energy Technology Data Exchange (ETDEWEB)

    Bower, L.

    2015-07-01

    Performance upgrade and equipment degradation are the primary impetuses for a nuclear power plant to engage in the large capital cost project of heat exchanger replacement. Along with attention to these issues, consideration of heat exchanger Codes and Standards, material improvements, thermal redesign, and configuration are essential for developing User’s Design Specifications for successful replacement projects. The User’s Design Specification is the central document in procuring ASME heat exchangers. Properly stated objectives for the heat exchanger replacement are essential for obtaining the materials, configurations and thermal designs best suited for the nuclear power plant. Additionally, the code of construction required and the applied manufacturing standard (TEMA or HEI) affects how the heat exchanger may be designed or configured to meet the replacement goals. Knowledge of how Codes and Standards affect design and configuration details will aid in writing the User’s Design Specification. Joseph Oat Corporation has designed and fabricated many replacement heat exchangers for the nuclear power industry. These heat exchangers have been constructed per ASME Section III to various Code-Years or ASME Section VIII-1 to the current Code-Year also in accordance with TEMA and HEI. These heat exchangers have been a range of like-for-like replacement to complete thermal, material and configuration redesigns. Several examples of these heat exchangers with their Code, Standard and specification implications are presented. (Author.

  2. Testosterone Replacement, Muscle Strength, and Physical Function

    Directory of Open Access Journals (Sweden)

    You-Seon Nam

    2018-05-01

    Full Text Available Muscle strength and physical function decrease in older men, as do testosterone levels. Nonetheless, the effects of testosterone replacement therapy on muscle strength and physical function remain inconclusive and equivocal. We conducted a rapid systematic review, the results of which showed that testosterone replacement does not affect muscle strength (measured by hand grip strength and leg muscle strength, although it may increase physical function (measured by the 6-minute walk test, Physical Activity Scale for the Elderly score, and other physical performance tests. However, most of the studies were conducted in the United States or Europe and did not include participants from Asian or other ethnic backgrounds; therefore, further studies are needed to evaluate the effects of testosterone replacement in a broader population.

  3. Replacement of the essential Dictyostelium Arp2 gene by its Entamoeba homologue using parasexual genetics

    Directory of Open Access Journals (Sweden)

    Fütterer Klaus

    2007-06-01

    Full Text Available Abstract Background Cell motility is an essential feature of the pathogenesis and morbidity of amoebiasis caused by Entamoeba histolytica. As motility depends on cytoskeletal organisation and regulation, a study of the molecular components involved is key to a better understanding of amoebic pathogenesis. However, little is known about the physiological roles, interactions and regulation of the proteins of the Entamoeba cytoskeleton. Results We have established a genetic strategy that uses parasexual genetics to allow essential Dictyostelium discoideum genes to be manipulated and replaced with modified or tagged homologues. Our results show that actin related protein 2 (Arp2 is essential for survival, but that the Dictyostelium protein can be complemented by E. histolytica Arp2, despite the presence of an insertion of 16 amino acids in an otherwise highly conserved protein. Replacement of endogenous Arp2 with myc-tagged Entamoeba or Dictyostelium Arp2 has no obvious effects on growth and the protein incorporates effectively into the Arp2/3 complex. Conclusion We have established an effective two-step method for replacing genes that are required for survival. Our protocol will allow such genes to be studied far more easily, and also allows an unambiguous demonstration that particular genes are truly essential. In addition, cells in which the Dictyostelium Arp2 has been replaced by the Entamoeba protein are potential targets for drug screens.

  4. Functional and molecular neuroimaging of menopause and hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    Erika eComasco

    2014-12-01

    Full Text Available The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. This review summarizes the findings of thirty-four studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri- and postmenopausal women treated with estrogen, or estrogen-progestagen replacement therapy. Seven studies using gonadotropin-releasing hormone agonist intervention as a model of hormonal withdrawal are also included. Cognitive paradigms are employed by the majority of studies evaluating the effect of unopposed estrogen or estrogen-progestagen treatment on peri- and postmenopausal women’s brain. In randomized-controlled trials, estrogen treatment enhances activation of fronto-cingulate regions during cognitive functioning, though in many cases no difference in cognitive performance was present. Progestagens seems to counteract the effects of estrogens. Findings on cognitive functioning during acute ovarian hormone withdrawal suggest a decrease in activation of the inferior frontal gyrus, thus essentially corroborating the findings in postmenopausal women. Studies of the cholinergic and serotonergic systems indicate these systems as biological mediators of hormonal influences on the brain. More, hormonal replacement appears to increase cerebral blood flow in cortical regions. On the other hand, studies on emotion processing in postmenopausal women are lacking. These results call for well-powered randomized-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal

  5. Renal function after elective total hip replacement

    DEFF Research Database (Denmark)

    Perregaard, Helene; Damholt, Mette B; Solgaard, Søren

    2016-01-01

    and the prevalence of chronic kidney disease (CKD) in an elective population of orthopedic patients undergoing primary total hip replacement, hypothesizing that chronic kidney disease predisposes to AKI. Patients and methods - This was a single-center, population-based, retrospective, registry-based cohort study...... involving all primary elective total hip replacements performed from January 2003 through December 2012. Patient demographics and creatinine values were registered. We evaluated the presence of CKD and AKI according to the international guidelines for kidney disease (KDIGO Acute Kidney Injury Workgroup 2013...... ). Results - 3,416 patients were included (2,064 females (60%)). AKI (according to KDIGO criteria) was seen in 75 patients (2.2%, 95% CI: 1.7-2.7) in the course of primary total hip replacement. Of these, 26 had pre-existing CKD of class 3-5. Pre-existing CKD of class 3-5, indicating moderately to severely...

  6. The cost function for the preventive - maintenance replacement problem

    OpenAIRE

    Vilaplana, Jose Perez

    1994-01-01

    Let a discounted continuous review preventive-maintenance replacement model be such that its total discounted cost is given by means of two functional equations. We assume that downtime is caused by equipment breakdowns, and the length of a given downtime is the time necessary to repair the equipment and set it back in operation. The periodic preventive replacement policy is to replace the equipment by a new identical equipment when service age X is reached, or when the equipment ...

  7. Enabling access to new WHO essential medicines: the case for nicotine replacement therapies

    Directory of Open Access Journals (Sweden)

    Cravioto Alejandro

    2010-11-01

    Full Text Available Abstract Nicotine replacement therapies (NRT are powerful tools for the successful treatment of nicotine addiction and tobacco use. The medicines are clinically effective, supported by the Framework Convention on Tobacco Control, and are now World Health Organization-approved essential medicines. Enabling global access to NRT remains a challenge given ongoing confusion and misperceptions about their efficacy, cost-effectiveness, and availability with respect to other tobacco control and public health opportunities. In this commentary, we review existing evidence and guidelines to make the case for global access to NRT highlighting the smoker's right to access treatment to sensibly address nicotine addiction.

  8. Operational management and eventual replacement of essential cooling water heat exchangers: a case study

    Energy Technology Data Exchange (ETDEWEB)

    King, P. [Babcock & Wilcox Canada Ltd., Cambridge, Ontario (Canada); Raught, D. [Arizona Public Service Company, Phoenix, Arizona (United States)

    2012-07-01

    Essential Cooling Water Heat Exchangers (ECW HXs) at Palo Verde Nuclear Generating Station are tubed with admiralty brass and cooled by pond water. A number of tube leaks caused by circumferential cracking occurred in the Unit 2 heat exchangers during the period from 1991 to 1993. Metallurgical examinations of removed tubes concluded that the failures were the result of stress corrosion cracking and that other corrosion degradation was also occurring. Until recently that degradation problem was effectively managed by a combination of tube sleeving, tube plugging, and ongoing inspections. Then in 2009, leakage problems re-emerged. Investigation showed that the leakage was again caused by corrosion cracking at the end of the tube sleeves. Continued management of the degradation by the methods previously used was considered to be not viable due to the unfavorable location of the cracking and a decision was subsequently taken to replace the Unit 2 heat exchangers. A significant problem was encountered with the tubing material of the first replacement heat exchanger as supplied for the heat exchanger manufacture at Babcock & Wilcox Canada. During filling of the shell side of the vessel for hydrostatic testing, water was seen leaking from three tubes. Investigation and correction of this condition involved a combination of measures including; i) inspections to find the defective tubes, ii) metallurgical examination to determine the cause of leakage and, iii) extra manufacturing and procurement activities to remove and replace the defective tubes. Eddy current inspection indicated axially oriented defects as the cause of the leakage. Metallographic examination of removed tubes confirmed the presence of through-wall axial defects and led to the conclusion that these stemmed from initial tube manufacture. In total, 67 tubes had to be removed; the replacement tubes were carefully inspected before installation. Despite the obvious schedule effects of this problem, the vessel

  9. Replacement

    Directory of Open Access Journals (Sweden)

    S. Radhakrishnan

    2014-03-01

    Full Text Available The fishmeal replaced with Spirulina platensis, Chlorella vulgaris and Azolla pinnata and the formulated diet fed to Macrobrachium rosenbergii postlarvae to assess the enhancement ability of non-enzymatic antioxidants (vitamin C and E, enzymatic antioxidants (superoxide dismutase (SOD and catalase (CAT and lipid peroxidation (LPx were analysed. In the present study, the S. platensis, C. vulgaris and A. pinnata inclusion diet fed groups had significant (P < 0.05 improvement in the levels of vitamins C and E in the hepatopancreas and muscle tissue. Among all the diets, the replacement materials in 50% incorporated feed fed groups showed better performance when compared with the control group in non-enzymatic antioxidant activity. The 50% fishmeal replacement (best performance diet fed groups taken for enzymatic antioxidant study, in SOD, CAT and LPx showed no significant increases when compared with the control group. Hence, the present results revealed that the formulated feed enhanced the vitamins C and E, the result of decreased level of enzymatic antioxidants (SOD, CAT and LPx revealed that these feeds are non-toxic and do not produce any stress to postlarvae. These ingredients can be used as an alternative protein source for sustainable Macrobrachium culture.

  10. Sexual Function before and after Total Hip Replacement: Narrative Review

    Directory of Open Access Journals (Sweden)

    Rotem Meiri, BPT

    2014-12-01

    Conclusions: The ability to move comfortably is included among the many physical and psychosocial factors influencing sexual functioning. Practitioners should be encouraged to question their THR patients about sexual concerns and to provide counseling related to physical and functional aspects of sexual activity. Rehabilitation that focuses specifically on activities of daily living of sex should include sexual counseling, therapeutic exercise, and advice regarding sexual positions. Rehabilitation provided by physical therapists may help decrease pain, and facilitate greater self‐awareness, self‐confidence, and improved body image, all of which encourage and affirm optimal sexual health. Meiri R, Rosenbaum TY, and Kalichman L. Sexual function before and after total hip replacement: Narrative review. Sex Med 2014;2:159–167.

  11. Functional and molecular neuroimaging of menopause and hormone replacement therapy

    DEFF Research Database (Denmark)

    Comasco, Erika; Frøkjær, Vibe; Sundström-Poromaa, Inger

    2014-01-01

    The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuat......The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone...... fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. The present review summarizes the findings of thirty-five studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri......-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal variations on the brain....

  12. Scientific Opinion on the essential composition of total diet replacements for weight control

    DEFF Research Database (Denmark)

    Tetens, Inge

    2015-01-01

    or authoritative bodies. Derived from the minimum content of macronutrients, the Panel proposed a minimum energy content of total diet replacements for weight control of 2 510 kJ/day (600 kcal/day). The Panel also advised on potential conditions and restrictions of use for these products....

  13. Familial Essential Tremor Studied With Functional Magnetic Resonance Imaging

    Science.gov (United States)

    Hernandez, A.; Salgado, P.; Gil, A.; Barrios, F. A.

    2003-09-01

    Functional Magnetic Resonance Imaging has become an important analytical tool to study neurodegenerative diseases. We applied the EPI-BOLD functional Magnetic Resonance Imaging technique to acquire functional images of patients with familial essential tremor (FET) disorder and healthy control volunteers, during a motor task activity. Functional and anatomic images were used to produce the brain activation maps of the patients and volunteers. These functional maps of the primary somatosensorial and motor cortexes of patients and control subjects were compared for functional differences per subject. The averaged functional brain images of eight of each case were acquired were, it can be clearly observed the differences in active zones. The results presented in this work show that there are differences in the functional maps during motor task activation between control subjects and FET patients suggesting a cerebral functional reorganization that can be mapped with BOLD-fMRI.

  14. Functional Tooth Regeneration Using a Bioengineered Tooth Unit as a Mature Organ Replacement Regenerative Therapy

    Science.gov (United States)

    Imamura, Aya; Ogawa, Miho; Yasukawa, Masato; Yamazaki, Hiromichi; Morita, Ritsuko; Ikeda, Etsuko; Nakao, Kazuhisa; Takano-Yamamoto, Teruko; Kasugai, Shohei; Saito, Masahiro; Tsuji, Takashi

    2011-01-01

    Donor organ transplantation is currently an essential therapeutic approach to the replacement of a dysfunctional organ as a result of disease, injury or aging in vivo. Recent progress in the area of regenerative therapy has the potential to lead to bioengineered mature organ replacement in the future. In this proof of concept study, we here report a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. The bioengineered tooth unit restored enough the alveolar bone in a vertical direction into an extensive bone defect of murine lower jaw. Engrafted bioengineered tooth displayed physiological tooth functions such as mastication, periodontal ligament function for bone remodeling and responsiveness to noxious stimulations. This study thus represents a substantial advance and demonstrates the real potential for bioengineered mature organ replacement as a next generation regenerative therapy. PMID:21765896

  15. Functionality of Inulin as a Sucrose Replacer in Cookie Baking

    Science.gov (United States)

    Inulin was evaluated as a sucrose replacer for healthy cookie production with benefits of low glycemic impact and prebiotic soluble fiber. Sucrose (as a reference) and three inulin products of different concentrations (as soluble fibers) were used to explore the effects of sugar-replacer type on so...

  16. Dynamic foot function changes following total knee replacement surgery.

    Science.gov (United States)

    Levinger, Pazit; Menz, Hylton B; Morrow, Adam D; Bartlett, John R; Feller, Julian A; Fotoohabadi, Mohammad R; Bergman, Neil R

    2012-12-01

    Individuals with knee osteoarthritis (OA) have flatter/more pronated feet than those without OA, but it is unclear whether altered foot posture and function are a cause or consequence of knee OA. The purpose of this study was to examine whether changes in foot posture and function occur after realignment of the knee following total knee replacement (TKR). Nineteen patients with predominantly medial compartment knee OA were tested prior to and 12 months after TKR. The Foot Posture Index (FPI) and Arch Index (AI) were measured as well as motion of the tibia, rearfoot and forefoot using a 3D motion analysis system incorporating a multisegment foot model. There were no significant changes in FPI or AI following TKR, however gait analysis revealed significant increases in tibial external rotation (-18.7 ± 7.0° vs -22.5 ± 8.7°, p=0.002), tibial transverse plane range of motion (-9.1 ± 4.6° vs -11.4 ± 6.1°, p=0.0028) and rearfoot range of motion in the frontal plane (8.6 ± 2.6° vs 10.4 ± 2.7°, p=0.002), and a decrease in rearfoot transverse plane range of motion (8.7 ± 5.3° vs 5.9 ± 4.1°, p=0.038) following the procedure. TKR produces no change in static foot posture, but results in significant changes in rearfoot kinematics during gait. These findings suggest that rearfoot motion compensates for changes in the alignment of the knee, highlighting the ability of the foot to accommodate for proximal skeletal malalignment. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Essential nontranslational functions of tRNA synthetases.

    Science.gov (United States)

    Guo, Min; Schimmel, Paul

    2013-03-01

    Nontranslational functions of vertebrate aminoacyl tRNA synthetases (aaRSs), which catalyze the production of aminoacyl-tRNAs for protein synthesis, have recently been discovered. Although these new functions were thought to be 'moonlighting activities', many are as critical for cellular homeostasis as their activity in translation. New roles have been associated with their cytoplasmic forms as well as with nuclear and secreted extracellular forms that affect pathways for cardiovascular development and the immune response and mTOR, IFN-γ and p53 signaling. The associations of aaRSs with autoimmune disorders, cancers and neurological disorders further highlight nontranslational functions of these proteins. New architecture elaborations of the aaRSs accompany their functional expansion in higher organisms and have been associated with the nontranslational functions for several aaRSs. Although a general understanding of how these functions developed is limited, the expropriation of aaRSs for essential nontranslational functions may have been initiated by co-opting the amino acid-binding site for another purpose.

  18. Essential Non-Translational Functions of tRNA Synthetases

    Science.gov (United States)

    Guo, Min; Schimmel, Paul

    2013-01-01

    Nontranslational functions of vertebrate aminoacyl tRNA synthetases (aaRSs), which catalyze the production of aminoacyl-tRNAs for protein synthesis, have recently been discovered. While these new functions were thought to be ‘moonlighting activities’, many are as critical for cellular homeostasis as the activity in translation. New roles have been associated with cytoplasmic forms as well as with nuclear and secreted extracellular forms that impact pathways for cardiovascular development, the immune response, and mTOR, IFN-γ and p53 signaling. The associations of aaRSs with autoimmune disorders, cancers and neurological disorders further highlight nontranslational functions of these proteins. Novel architecture elaborations of the aaRSs accompany their functional expansion in higher organisms and have been associated with the nontranslational functions for several aaRSs. While a general understanding of how these functions developed is limited, the expropriation of aaRSs for essential nontranslational functions may have been initiated by co-opting the amino acid binding site for another purpose. PMID:23416400

  19. Pregnancy after Prosthetic Aortic Valve Replacement: How Do We Monitor Prosthetic Valvular Function during Pregnancy?

    Directory of Open Access Journals (Sweden)

    Nicole Sahasrabudhe

    2018-01-01

    Full Text Available Background. With modern medicine, many women after structural heart repair are deciding to experience pregnancy. There is a need for further study to identify normal echocardiographic parameters to better assess prosthetic valvular function in pregnancy. In addition, a multidisciplinary approach is essential in managing pregnant patients with complex cardiac conditions. Case. A 22-year-old nulliparous woman with an aortic valve replacement 18 months prior to her pregnancy presented to prenatal care at 20-week gestation. During her prenatal care, serial echocardiography showed a significant increase in the mean gradient across the prosthetic aortic valve. Multidisciplinary management and a serial echocardiography played an integral role in her care that resulted in a successful spontaneous vaginal delivery without complications. Conclusion. Further characterization of the normal echocardiographic parameters in pregnant patients with prosthetic valves is critical to optimize prenatal care for this patient population. This case report is novel in that serial echocardiograms were obtained throughout prenatal care, which showed significant changes across the prosthetic aortic valve. Teaching Points. (1 Further study is needed to identify normal echocardiographic parameters to best assess prosthetic valvular function in pregnancy. (2 Multidisciplinary management is encouraged to optimize prenatal care for women with prosthetic aortic valve replacements.

  20. Postoperative Recovery of Mechanical Muscle Function in Hip Replacement Patients

    DEFF Research Database (Denmark)

    Jensen, Carsten; Aagaard, Per; Overgaard, Søren

    2011-01-01

    old hip patients.   MATERIAL AND METHODS Patients: Forty elderly patients (age 55 ± 6, BMI 27.5 ± 4.1) with unilateral osteoarthritis participated in this prospectively study and were randomized to either total or resurfacing hip replacement. All implants inserted by two senior surgeons using only...

  1. Increasing intake of essential fatty acids from milk replacer benefits performance, immune responses, and health of preweaned Holstein calves.

    Science.gov (United States)

    Garcia, M; Shin, J H; Schlaefli, A; Greco, L F; Maunsell, F P; Thatcher, W W; Santos, J E P; Staples, C R

    2015-01-01

    The objective was to evaluate the effect of feeding increasing amounts of essential fatty acids (FA) in milk replacer (MR) during the first 60 d of life on growth, health, and immunity of Holstein calves. Calves were born from dams fed low concentrations of total and essential FA during the lasT2 mo of pregnancy. Newborn calves were blocked by sex and parity of the dam and assigned randomly to receive 1 of 4 MR treatments (T). Hydrogenated coconut oil and soybean oil were mixed with emulsifier and commercial MR powder to prepare the following 4 MR containing 0.119 and 0.007 (T1), 0.187 and 0.017 (T2), 0.321 and 0.036 (T3), and 0.593 and 0.076 (T4) g of intake per kg of metabolic body weight (BW(0.75)) of linoleic acid and α-linolenic acid, respectively. At 30 d of life, concentrations of essential FA (linoleic acid and α-linolenic acid) in liver increased, whereas concentrations of C12:0, C14:0, C16:0, and C20:3n-9 decreased linearly with increasing intake of essential FA. Body weight gain and feed efficiency were optimized when male calves consumed T2, whereas gain by female calves tended to increase linearly with increasing intake of essential FA during the first 30 d of age. However, these responses to treatment were not maintained after initiation of concentrate feeding at 31 d of life. Over the 60-d preweaning period, wither and hip heights were improved in both sexes as intake of essential FA increased up to T3. Some measures of health and immunity were affected by replacing some coconut oil with soybean oil. Severity of diarrhea tended to decrease linearly; plasma concentrations of haptoglobin during diarrhea were lower in T2, T3, and T4; phagocytosis by blood neutrophils tended to peak for calves fed T2; in vitro proliferation of stimulated blood lymphocytes was greater for calves fed T2; in vitro stimulated blood cells produced more IFN-γ (up to T3 for males and T2 for females), concentrations of serum IgG against ovalbumin injections were increased in

  2. The algebras of bounded and essentially bounded Lebesgue measurable functions

    Directory of Open Access Journals (Sweden)

    Mortini Raymond

    2017-04-01

    Full Text Available Let X be a set in ℝn with positive Lebesgue measure. It is well known that the spectrum of the algebra L∞(X of (equivalence classes of essentially bounded, complex-valued, measurable functions on X is an extremely disconnected compact Hausdorff space.We show, by elementary methods, that the spectrum M of the algebra ℒb(X, ℂ of all bounded measurable functions on X is not extremely disconnected, though totally disconnected. Let ∆ = { δx : x ∈ X} be the set of point evaluations and let g be the Gelfand topology on M. Then (∆, g is homeomorphic to (X, Τdis,where Tdis is the discrete topology. Moreover, ∆ is a dense subset of the spectrum M of ℒb(X, ℂ. Finally, the hull h(I, (which is homeomorphic to M(L∞(X, of the ideal of all functions in ℒb(X, ℂ vanishing almost everywhere on X is a nowhere dense and extremely disconnected subset of the Corona M \\ ∆ of ℒb(X, ℂ.

  3. Functional design criteria radioactive liquid waste line replacement, Project W-087. Revision 3

    International Nuclear Information System (INIS)

    McVey, C.B.

    1994-01-01

    This document provides the functional design criteria for the 222-S Laboratory radioactive waste drain piping and transfer pipeline replacement. The project will replace the radioactive waste drain piping from the hot cells in 222-S to the 219-S Waste Handling Facility and provide a new waste transfer route from 219-S to the 244-S Catch Station in Tank Farms

  4. Visual function alterations in essential tremor: A case report

    Directory of Open Access Journals (Sweden)

    David P. Piñero

    2015-09-01

    Full Text Available Our purpose is to report alterations in contrast sensitivity function (CSF and in the magno, parvo and koniocellular visual pathways by means of a multichannel perimeter in case of an essential tremor (ET. A complete evaluation of the visual function was performed in a 69-year old patient, including the analysis of the chromatic discrimination by the Fansworth–Munsell 100 hue test, the measurement of the CSF by the CSV-1000E test, and the detection of potential alteration patterns in the magno, parvo and koniocellular visual pathways by means of a multichannel perimeter. Visual acuity and intraocular pressure (IOP were within the ranges of normality in both eyes. No abnormalities were detected in the fundoscopic examination and in the optical coherence tomography (OCT exam. The results of the color vision examination were also within the ranges of normality. A significant decrease in the achromatic CSFs for right eye (RE and left eye (LE was detected for all spatial frequencies. The statistical global values provided by the multichannel perimeter confirms that there were significant absolute sensitivity losses compared to the normal pattern in RE. In the LE, only a statistically significant decrease in sensitivity was detected for the blue-yellow (BY channel. The pattern standard deviation (PSD values obtained in our patient indicated that there were significant localized losses compared to the normality pattern in the achromatic channel of the RE and in the red-green (RG channel of the LE. Some color vision alterations may be present in ET that cannot be detected with conventional color vision tests, such as the FM 100 Hue.

  5. Functions and Requirements and Specifications for Replacement of the Computer Automated Surveillance System (CASS)

    International Nuclear Information System (INIS)

    SCAIEF, C.C.

    1999-01-01

    This functions, requirements and specifications document defines the baseline requirements and criteria for the design, purchase, fabrication, construction, installation, and operation of the system to replace the Computer Automated Surveillance System (CASS) alarm monitoring

  6. Optimal replacement time estimation for machines and equipment based on cost function

    OpenAIRE

    J. Šebo; J. Buša; P. Demeč; J. Svetlík

    2013-01-01

    The article deals with a multidisciplinary issue of estimating the optimal replacement time for the machines. Considered categories of machines, for which the optimization method is usable, are of the metallurgical and engineering production. Different models of cost function are considered (both with one and two variables). Parameters of the models were calculated through the least squares method. Models testing show that all are good enough, so for estimation of optimal replacement time is ...

  7. Optimal replacement time estimation for machines and equipment based on cost function

    Directory of Open Access Journals (Sweden)

    J. Šebo

    2013-01-01

    Full Text Available The article deals with a multidisciplinary issue of estimating the optimal replacement time for the machines. Considered categories of machines, for which the optimization method is usable, are of the metallurgical and engineering production. Different models of cost function are considered (both with one and two variables. Parameters of the models were calculated through the least squares method. Models testing show that all are good enough, so for estimation of optimal replacement time is sufficient to use simpler models. In addition to the testing of models we developed the method (tested on selected simple model which enable us in actual real time (with limited data set to indicate the optimal replacement time. The indicated time moment is close enough to the optimal replacement time t*.

  8. Effect of pre-operative neuromuscular training on functional outcome after total knee replacement

    DEFF Research Database (Denmark)

    Huber, Erika O; de Bie, Rob A; Roos, Ewa M.

    2013-01-01

    Total Knee Replacement (TKR) is the standard treatment for patients with severe knee osteoarthritis (OA). Significant improvement in pain and function are seen after TKR and approximately 80% of patients are very satisfied with the outcome. Functional status prior to TKR is a major predictor...... of outcome after the intervention. Thus, improving functional status prior to surgery through exercise may improve after surgery outcome. However, results from several previous trials testing the concept have been inconclusive after surgery....

  9. Knowledge of native valve anatomy is essential in follow-up of patients after aortic valve replacement

    NARCIS (Netherlands)

    Cozijnsen, Luc; van der Zaag-Loonen, Hester J.; Cozijnsen, Martinus A.; Braam, Richard L.; Heijmen, Robin H.; Mulder, Barbara J. M.

    2016-01-01

    Background: After aortic valve replacement (AVR), bicuspid aortic valve (BAV) patients continue to be at risk of aortic complications. Therefore, knowledge of native valve anatomy is important for follow-up. We aimed to determine the extent of which the presence of BAV disease is known in a regional

  10. Functional exercise after total hip replacement (FEATHER): a randomised control trial.

    LENUS (Irish Health Repository)

    Monaghan, Brenda

    2012-11-01

    Prolonged physical impairments in range of movement, postural stability and walking speed are commonly reported following total hip replacement (THR). It is unclear from the current body of evidence what kind of exercises should be performed to maximize patient function and quality of life.

  11. Educating Nursing Students with Disabilities: Replacing Essential Functions with Technical Standards for Program Entry Criteria

    Science.gov (United States)

    Matt, Susan B.; Maheady, Donna; Fleming, Susan E.

    2015-01-01

    Across the globe, students with disabilities have been increasing in prevalence in higher education settings. In the twenty-first century the struggle to include individuals with disabilities into nursing schools and workplaces continues in different parts of the world. Historically, entry criteria in nursing schools have been based on essential…

  12. Waiting for total knee replacement surgery: factors associated with pain, stiffness, function and quality of life

    Directory of Open Access Journals (Sweden)

    Dionne Clermont E

    2009-05-01

    Full Text Available Abstract Background Recent evidences show that education and rehabilitation while waiting for knee replacement have positive effects on the patients' health status. Identification of factors associated with worse pain, function and health-related quality of life (HRQoL while waiting for surgery could help develop pre-surgery rehabilitation interventions that target specifically these factors and prioritize patients that may benefit the most from them. The objectives of this study were to measure pain, stiffness, function and HRQoL in patients at enrolment on waiting lists for knee replacement and to identify demographic, clinical, socioeconomic and psychosocial characteristics associated with these outcomes. Methods This study is part of a broader study measuring the effects of pre-surgery wait in patients scheduled for knee replacement. From 02/2006 to 09/2007, 197 patients newly scheduled for total knee replacement were recruited from the waiting lists of three university hospitals in Quebec City, Canada. Pain, stiffness and function were measured with the Western Ontario and McMaster Osteoarthritis Index (WOMAC and HRQoL was measured with the SF-36 Health Survey. Stepwise multiple regression analysis was used to assess the strength of the associations between the independent variables and the WOMAC and SF-36 scores. Results The scores of all eight HRQoL physical and mental domains of the SF-36 were significantly lower than aged matched Canadian normative data (p Conclusion Patients waiting for knee replacement have poor function and HRQoL. Characteristics that were found to be associated with these outcomes could help develop pre-surgery rehabilitation program and prioritize patients that may benefit the most from them. Such programs could include interventions to reduce psychological distress, therapeutic exercises targeting both knees and weight loss management.

  13. The influence of optimism on functionality after total hip replacement surgery.

    Science.gov (United States)

    Balck, Friedrich; Lippmann, Maike; Jeszenszky, Csilla; Günther, Klaus-Peter; Kirschner, Stephan

    2016-08-01

    Among other factors, optimism has been shown to significantly influence the course of some diseases (cancer, HIV, coronary heart disease). This study investigated whether optimism of a patient before a total hip replacement can predict the functionality of the lower limbs 3 and 6 months after surgery. A total of 325 patients took part in the study (age: 58.7 years; w: 55%). The functionality was measured with the Western Ontario and McMaster Universities arthrosis index, and optimism with the Life Orientation Test. To analyse the influences of age, gender and optimism, general linear models were calculated. In optimistic patients, functionality improved significantly over time. The study showed a clear influence of dispositional optimism on the recovery after total hip replacement in the first 3 months after surgery. © The Author(s) 2015.

  14. Vascular Function and Angiogenesis in Aging and Essential Hypertension

    DEFF Research Database (Denmark)

    Gliemann, Lasse

    antioxidants  In aged individuals, the presence of ROS may be excessive, due to increased ROS formation and reduced antioxidant defense capacity. Such an increase in oxidative stress could lead to cell damage and inflammation. The present work shows that a period of exercise training in aged men can lower...... markers of basal oxidative stress and inflammation in skeletal muscle. The effect of training on markers of oxidative stress was likely, at least in part, due to a increase in skeletal muscle levels of SOD2, as the potential for ROS formation actually increased as evidenced by an increase...... in the expression of NAD(P)H oxidase. This latter finding of a training induced increase in NAD(P)H oxidase emphasizes the importance of ROS for muscle function and adaptation and to some extent even questions the theory of harmful oxidative stress in healthy aged individuals. Our studies were not able to support...

  15. The efficiency of functional mitochondrial replacement in Saccharomyces species has directional character

    DEFF Research Database (Denmark)

    Sulo, P.; Spirek, M.; Soltesova, A.

    2003-01-01

    Optimal interactions among nuclear and mitochondria-coded proteins are required to assemble functional complexes of mitochondrial oxidative phosphorylation. The communication between the nuclear and mitochondrial genomes has been studied by transplacement of mitochondria from related species...... in the S. cerevisiae mitochondrial DNA. Our results suggest that, apart from evolutionary distance, the direction of mitochondrial replacement could play a significant role in installing the complete (wild-type-like) interaction between mitochondria and nuclei from different species....

  16. Restoration of mammillothalamic functional connectivity through thiamine replacement therapy in Wernicke's encephalopathy.

    Science.gov (United States)

    Kim, Eosu; Ku, Jeonghun; Jung, Young-Chul; Lee, Hyeongrae; Kim, Sun I; Kim, Jae-Jin; Namkoong, Kee; Song, Dong-Ho

    2010-08-02

    Resting-state functional MRI (fMRI) is now providing further understanding of neuropsychiatric illnesses. However, its practical applicability in the clinical realms is still questionable. Here we report three consecutive followed-up resting-state fMRI data in a single case with Wernicke encephalopathy before and after high-dose thiamine replacement therapy ranging over 20 months. We measured the mammillothalamic functional connectivity strength between the first ROI (mammillary body) and a voxel which showed the highest co-activation among voxels within the anterior thalamus (the second ROI) to enhance the specificity of the functional connectivity data. We found that the time-series changes in the mammillothalamic functional connectivity generally paralleled to the changes in delayed verbal and nonverbal recall memory scores in the left and right hemisphere, respectively. Among these, the left-side connectivity and delayed verbal recall score seemed to be related to the overall clinical status change. Modified directed transfer function (dDTF) analysis also identified significant information flows with mammillary-to-thalamic direction except at the acute illness state. Our findings, though preliminary in nature, suggest the practical applicability of resting-state fMRI to trace an effect of thiamine replacement therapy on the memory tract function in Wernicke encephalopathy at single-patient level. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  17. The impact of changes in LVEF and renal function on the prognosis of ICD patients after elective device replacement.

    Science.gov (United States)

    Vandenberk, Bert; Robyns, Tomas; Garweg, Christophe; Floré, Vincent; Foulon, Stefaan; Voros, Gabor; Ector, Joris; Willems, Rik

    2017-10-01

    A proportion of patients with an implantable cardioverter-defibrillator (ICD) in prevention of sudden cardiac death will only receive their first appropriate ICD therapy (AT) after device replacement. Clinical reassessment at the time of replacement could be helpful to guide the decision to replace or not in the future. All patients with an ICD for primary or secondary prevention in ischemic (ICM) or nonischemic cardiomyopathy were included in a single-center retrospective registry. The association of changes in left ventricular ejection fraction (LVEF; cut-off at 35%), worsening renal function (decrease in estimated glomerular filtration rate > 15 mL/min), and worsening New York Heart Association class at elective device replacement with mortality and AT was analyzed using adjusted Cox regression analysis. A total of 238 (33%) out of 727 patients received elective device replacement (86.1% male, 74.4% ICM, 42.9% primary prevention). During this replacement 20.2% received a device upgrade. The mean time to replacement was 6.4 ± 2.0 years and mean follow-up after replacement was 3.4 ± 3.0 years. Of patients who did not receive AT before replacement 23.1% received their first AT after replacement. Worsening renal function (hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.50-5.18) and a consistently LVEF ≤35% compared to a consistently LVEF >35% (HR 2.15, 95% CI 1.10-4.19) at the time of replacement were independent predictors of mortality. Independent predictors of first AT after replacement could not be identified. Although reassessment of LVEF and renal function at replacement can be helpful in predicting total mortality, the clinical utility to guide reimplantation seemed limited. Our experience indicates that approximately 25% of patients received their first AT only after replacement. © 2017 Wiley Periodicals, Inc.

  18. Improving arm function by prosthetic limb replacement in a patient with severe arthrogryposis multiplex congenita.

    Science.gov (United States)

    Salminger, Stefan; Roche, Aidan D; Sturma, Agnes; Hruby, Laura A; Aszmann, Oskar C

    2016-10-05

    In patients with severe bilateral congenital arm deficiencies, even simple activities of daily living, such as feeding, may be major challenges. We report here a case of a patient with arthrogryposis multiplex congenita affecting all 4 extremities, who underwent prosthetic replacement after elective transhumeral amputation of his right functionless arm. A 22-year-old man with arthrogryposis multiplex congenita had severe deficits of his upper limbs. Previous surgeries for upper and lower limbs had enabled this patient to walk without aids; however, his upper limbs remained severely impaired. After prosthetic rehabilitation, including nerve and muscle transfers, a carefully planned elective amputation, signal processing and a comprehensive rehabilitation programme, the patient was able to independently conduct normal activities of daily living that had hitherto been impossible. The Disabilities of the Arm, Shoulder and Hand measure improved from 73.3 to 44.2, the Action Research Arm Test improved from 10 to 18 out of 57 points and the Southampton Hand Assessment Procedure improved from 8 to 23 after prosthetic replacement. Prosthetic replacement can improve upper limb function in patients with severe congenital limb deficiencies. In the case reported here, functional rehabilitation had a positive impact on the patient's quality of life and self-confidence, as he integrated the prosthesis into his body image.

  19. Twin Valve Caval Stent for Functional Replacement of Incompetent Tricuspid Valve: A Feasibility Animal Study

    International Nuclear Information System (INIS)

    Sochman, Jan; Peregrin, Jan H.; Pavcnik, Dusan; Uchida, Barry T.; Timmermans, Hans A.; Shimohira, Masashi; Choi, Young Ho; Keller, Frederick S.; Rösch, Josef

    2011-01-01

    Objective: To evaluate feasibility of a twin valve caval stent (TVCS) for functional replacement of an incompetent tricuspid valve (TV) in an acute animal study. Methods: One swine and three sheep were used in the study. TVCS placement was tested in a swine with a normal TV. TVCS function was tested in three sheep with TV regurgitation created by papillary muscle avulsion. Cardiac angiograms and pressure measurements were used to evaluate TVCS function. Two sheep were studied after fluid overload. Results: TVCS was percutaneously placed properly at the central portions of the superior vena cava (SVC) and inferior vena cava (IVC) in the swine. Papillary muscle avulsion in three sheep caused significant tricuspid regurgitation with massive reflux into the right atrium (RA) and partial reflux into the SVC and IVC. TVCS placement eliminated reflux into the SVC and IVC. After fluid overload, there was enlargement of the right ventricle and RA and significant increase in right ventricle, RA, SVC, and IVC pressures, but no reflux into the IVC and SVC. Conclusion: The results of this feasibility study justify detailed evaluation of TVCS insertion for functional chronic replacement of incompetent TV.

  20. STUDY OF FUNCTIONAL RESULTS OF CEMENTED TOTAL HIP REPLACEMENT BY MOORE’S APPROACH

    Directory of Open Access Journals (Sweden)

    Arunim

    2016-02-01

    Full Text Available INTRODUCTION The total hip replacement (THR has probably become the surgical procedure of choice for vide variety of hip joint disabling diseases. The prosthesis used for THR is often grouped into cemented, cement-less and hybrid ones. There has been increasing trends in use of cement-less components citing more number of complications namely loosening, increased infection rate etc. however with additional cost factors as well. We conducted this study to ascertain whether in a developing country like ours should we really switch over to un-cemented hip replacements dreading such complications or can we still use cemented prosthesis with equally good if not better results. METHODS A study of functional results of cemented total hip replacement was done in patients with varied age groups ranging from 40 years to 75 years with the average age being 54.8 years. 20 patients with 21 diseased hips were treated with cemented total hip replacement by Moore’s posterior approach at NSCB Subharti medical college, Meerut, UP from December 2010 to December 2013 and reviewed thereafter with an average follow-up period of 4.2 years. Average surgical time required was one and half hour. Patients were asked to come for follow up on 1st month, 3rd month and 6th month and then every 6 months and were assessed as per modified Harris Hip Score. RESULTS All the patients were evaluated according to the Modified Harris Hip Scoring system. The results showed 14(67% hips with excellent results, 4(19% with good results, and 3(14% hips with fair results. No poor outcome was noted in this study. 2 cases of dislocation (10% were noted one on the 5th post-operative day and the other occurred after the patient was discharged from the institution. CONCLUSIONS The management of diseased and destroyed hips with chronic pain with cemented total hip replacement is effective and gives stable, mobile and painless hip joint to the patient. Functional results are excellent and

  1. Mechanisms of function and disease of natural and replacement heart valves.

    Science.gov (United States)

    Schoen, Frederick J

    2012-01-01

    Over the past several decades, there has been substantial progress toward understanding the mechanisms of heart valve function and dysfunction. This review summarizes an evolving conceptual framework of heart valve functional structure, developmental biology, and pathobiology and explores the implications of key insights. I emphasize: (a) valve cell and extracellular matrix biology and the impact of biomechanical factors on function, homeostasis, environmental adaptation, and key pathological processes; (b) the role of developmental processes, valvular cell behavior, and extracellular matrix remodeling in congenital and acquired valve abnormalities; and (c) the cell/matrix biology of degeneration in replacement tissue valves. I also summarize how these considerations may ultimately inform the potential for prevention and treatment of major diseases and potentially therapeutic regeneration of the cardiac valves. Recent advances and opportunities for research and clinical translation are highlighted.

  2. Prosthetic replacement of the medial meniscus in cadaveric knees - Does the prosthesis mimic the functional behavior of the native meniscus?

    NARCIS (Netherlands)

    Tienen, TG; Verdonschot, N; Heijkants, RGJC; Buma, R; Scholten, JGF; van Kampen, A; Veth, RPH

    2004-01-01

    Meniscus replacement by a polymer meniscus prosthesis in dogs resulted in generation of new meniscal tissue. Hypothesis: Optimal functioning of the prosthesis would involve realistic deformation and motion patterns of the prosthesis during knee joint motion. Study Design: Controlled laboratory

  3. Prosthetic replacement of the medial meniscus in cadaveric knees: does the prosthesis mimic the functional behavior of the native meniscus?

    NARCIS (Netherlands)

    Tienen, T.G. van; Verdonschot, N.J.J.; Heijkants, R.G.J.C.; Buma, P.; Scholten, J.G.; Kampen, A. van; Veth, R.P.H.

    2004-01-01

    Meniscus replacement by a polymer meniscus prosthesis in dogs resulted in generation of new meniscal tissue. HYPOTHESIS: Optimal functioning of the prosthesis would involve realistic deformation and motion patterns of the prosthesis during knee joint motion. STUDY DESIGN: Controlled laboratory

  4. Replacing leads by self-energies using non-equilibrium Green's functions

    International Nuclear Information System (INIS)

    Michael, Fredrick; Johnson, M.D.

    2003-01-01

    Open quantum systems consist of semi-infinite leads which transport electrons to and from the device of interest. We show here that within the non-equilibrium Green's function technique for continuum systems, the leads can be replaced by simple c-number self-energies. Our starting point is an approach for continuum systems developed by Feuchtwang. The reformulation developed here is simpler to understand and carry out than the somewhat unwieldly manipulations typical in the Feuchtwang method. The self-energies turn out to have a limited variability: the retarded self-energy Σ r depends on the arbitrary choice of internal boundary conditions, but the non-equilibrium self-energy or scattering function Σ which determines transport is invariant for a broad class of boundary conditions. Expressed in terms of these self-energies, continuum non-equilibrium transport calculations take a particularly simple form similar to that developed for discrete systems

  5. Immediate functional loading of implants in single tooth replacement: a prospective clinical multicenter study.

    Science.gov (United States)

    Donati, Mauro; La Scala, Vincenzo; Billi, Mauro; Di Dino, Biagio; Torrisi, Paolo; Berglundh, Tord

    2008-08-01

    The aim of the present study was to evaluate the outcome of immediate functional loading of implants in single-tooth replacement using two different installation procedures. One hundred and fifty-one subjects, who required single-tooth rehabilitation in the area of 15-25 and 35-45, were enrolled in eight private clinics in Italy. The implant sites were randomly allocated to one of the following treatment groups. In the control group, in which a standard preparation procedure for implant placement and submerged healing of the implant was used, abutment connection and loading of the implants were performed 3 months after installation. In the test group 1, a standard preparation procedure for the implant placement and immediate functional loading of implant was carried out. In the test 2 group, however, a modified implant installation procedure (osteotome technique) was used followed by immediate functional loading of the implant. Clinical and radiographic examinations were performed at 3 and 12 months of follow-up at all sites. Three implants (5.5%) from the test 2 group (osteotome preparation) and one (2%) from the test 1 group (conventional drill preparation) failed to integrate and were removed one and three months after implant installation. The mean marginal bone loss assessed at 12 months was 0.31 mm (test 1), 0.25 mm (test 2) and 0.38 mm (control) (no statistically significant differences were found between the three treatment groups.) It is suggested that immediate functional loading of implants that are placed with a conventional installation technique and with sufficient primary stability may be considered as a valid treatment alternative in a single-tooth replacement.

  6. Hormone Replacement Therapy and Physical Function in Healthy Older Men. Time to Talk Hormones?

    Science.gov (United States)

    Giannoulis, Manthos G.; Martin, Finbarr C.; Nair, K. Sreekumaran; Umpleby, A. Margot

    2012-01-01

    Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established

  7. Hormone replacement therapy and physical function in healthy older men. Time to talk hormones?

    Science.gov (United States)

    Giannoulis, Manthos G; Martin, Finbarr C; Nair, K Sreekumaran; Umpleby, A Margot; Sonksen, Peter

    2012-06-01

    Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established.

  8. Improvement of a new rotation function for molecular replacement by designing new scoring functions and dynamic correlation coefficient

    Science.gov (United States)

    Jiang, Fan; Ding, Wei

    2010-10-01

    A previously published new rotation function has been improved by using a dynamic correlation coefficient as well as two new scoring functions of relative entropy and mean-square-residues to make the rotation function more robust and independent of a specific set of weights for scoring and ranking. The previously described new rotation function calculates the rotation function of molecular replacement by matching the search model directly with the Patterson vector map. The signal-to-noise ratio for the correct match was increased by averaging all the matching peaks. Several matching scores were employed to evaluate the goodness of matching. These matching scores were then combined into a single total score by optimizing a set of weights using the linear regression method. It was found that there exists an optimal set of weights that can be applied to the global rotation search and the correct solution can be ranked in the top 100 or less. However, this set of optimal weights in general is dependent on the search models and the crystal structures with different space groups and cell parameters. In this work, we try to solve this problem by designing a dynamic correlation coefficient. It is shown that the dynamic correlation coefficient works for a variety of space groups and cell parameters in the global search of rotation function. We also introduce two new matching scores: relative entropy and mean-square-residues. Last but not least, we discussed a valid method for the optimization of the adjustable parameters for matching vectors.

  9. Improved left ventricular function after growth hormone replacement in patients with hypopituitarism: assessment with radionuclide angiography

    International Nuclear Information System (INIS)

    Cuocolo, A.; Nicolai, E.; Colao, A.; Longobardi, S.; Cardei, S.; Fazio, S.; Merola, B.; Lombardi, G.; Sacca, L.; Salvatore, M.

    1996-01-01

    Prolonged growth hormone deficiency (GHD) leads to marked cardiac dysfunction; however, whether reversal of this abnormality may be achieved after specific replacement therapy has not yet been completely clarified. Fourteen patients with childhood-onset GHD (nine men and five women, mean age 27±4 years) and 12 normal control subjects underwent equilibrium radionuclide angiography under control conditions at rest. Patients with GHD were also studied 6 months after recombinant human (rh) GH treatment (0.05 IU/kg per day). Normal control subjects and patients with GHD did not differ with respect to age, gender and heart rate. In contrast, left ventricular ejection fraction (53%±9% vs 66%±6%, P 2 , P 2 , P 2 , P 2 , P <0.01) was observed in GHD patients. In conclusion, prolonged lack of GH leads to impaired left ventricular function at rest. Reversal of this abnormality may be observed after 6 months of specific replacement therapy in patients with childhood-onset GHD. (orig.). With 4 figs., 1 tab

  10. Combining Shigella Tn-seq data with gold-standard E. coli gene deletion data suggests rare transitions between essential and non-essential gene functionality.

    Science.gov (United States)

    Freed, Nikki E; Bumann, Dirk; Silander, Olin K

    2016-09-06

    Gene essentiality - whether or not a gene is necessary for cell growth - is a fundamental component of gene function. It is not well established how quickly gene essentiality can change, as few studies have compared empirical measures of essentiality between closely related organisms. Here we present the results of a Tn-seq experiment designed to detect essential protein coding genes in the bacterial pathogen Shigella flexneri 2a 2457T on a genome-wide scale. Superficial analysis of this data suggested that 481 protein-coding genes in this Shigella strain are critical for robust cellular growth on rich media. Comparison of this set of genes with a gold-standard data set of essential genes in the closely related Escherichia coli K12 BW25113 revealed that an excessive number of genes appeared essential in Shigella but non-essential in E. coli. Importantly, and in converse to this comparison, we found no genes that were essential in E. coli and non-essential in Shigella, implying that many genes were artefactually inferred as essential in Shigella. Controlling for such artefacts resulted in a much smaller set of discrepant genes. Among these, we identified three sets of functionally related genes, two of which have previously been implicated as critical for Shigella growth, but which are dispensable for E. coli growth. The data presented here highlight the small number of protein coding genes for which we have strong evidence that their essentiality status differs between the closely related bacterial taxa E. coli and Shigella. A set of genes involved in acetate utilization provides a canonical example. These results leave open the possibility of developing strain-specific antibiotic treatments targeting such differentially essential genes, but suggest that such opportunities may be rare in closely related bacteria.

  11. Changes in gait symmetry, gait velocity and self-reported function following total hip replacement.

    Science.gov (United States)

    Hodt-Billington, Caroline; Helbostad, Jorunn L; Vervaat, Willemijn; Rognsvåg, Turid; Moe-Nilssen, Rolf

    2011-09-01

    To investigate the magnitude of change at different time points in measures of gait symmetry, gait velocity and self-reported function following total hip replacement. Longitudinal with test occasions pre-surgery and 3, 6 and 12 months post-surgery. Thirty-four patients with hip osteoarthritis (mean age 63 years, standard deviation 11 years). Subjects walked back and forth along a 7-m walkway at slow, preferred and fast speed. Anteroposterior, vertical and mediolateral trunk symmetry was assessed by accelerometry, while single support symmetry, step-length symmetry and gait velocity was simultaneously assessed by an electronic walkway. Self-reported function was assessed by Hip disability and Osteoarthritis Outcome Score. Gait symmetry data were normalized for gait velocity. Changes between test occasions were reported as effect size. All measures showed effect sizes > 0.30 from pre-operative to 12-months postoperative assessments, and improvements were significant (p symmetry. In general, gait symmetry and gait velocity improved most 6 and 12 months postoperatively, while self-reported function improved most 3 months postoperatively. Early improvements were seen in self-reported function, suggesting immediate relief from stiffness and pain, while gait symmetry and velocity improved later postoperatively, suggesting that gait quality and performance require prolonged rehabilitation with postoperative guidance, muscular strengthening and motor relearning.

  12. Developing an "essential functions" rubric: purposes and applications for speech-language-hearing academic programs.

    Science.gov (United States)

    Horner, Jennifer; Schwarz, Ilsa; Jackson, Roberta; Johnstone, Patti; Mulligan, Moira; Roberts, Kathleen; Sohlberg, McKay Moore

    2009-01-01

    This article describes the purpose and application of an essential functions rubric for prospective and current students engaged in the study of communication sciences and disorders. Adopted in 2007 by the Council on Academic Programs in Communication Sciences and Disorders (CAPCSD), the essential functions rubric identifies core skills and attributes in five areas: communication, motor, intellectual-cognitive, sensory/observational, and behavioral/social. CAPCSD does not intend the rubric to be prescriptive but rather expects that it will be adapted to reflect the unique mission or circumstances of each academic program. The value of an essential functions rubric for academic programs is the opportunity it provides to educate students about the roles and responsibilities of the disciplines. A rubric also allows academic programs an objective basis for counseling students about professional expectations. Importantly, an essential functions rubric gives both students and programs opportunities to determine what, if any, accommodations might be employed to allow students who are otherwise qualified to help them succeed both academically and clinically.

  13. Cognitive Stimulation is Essential to Maintain and/or Improve the Cognitive Function of the Elderly

    OpenAIRE

    Telma Filipa Mendes Ramos; Lisete dos Santos Mendes Mónico; Pedro Miguel Parreira; Maria dos Anjos Coelho Rodrigues Dixe; Ana Ramos; César Fonseca

    2017-01-01

    Introduction: Cognitive stimulation is essential to maintain and / or improve the cognitive function of the elderly. Objectives: This study aimed to evaluate the impact of the application of a Cognitive Stimulation Program on the maintenance or improvement of the cognitive function of the elderly at the levels of orientation, memory, calculation and language. It was also intended to evaluate complementary measures of the impact of the intervention program, name- ly on the quality of life, dep...

  14. Respiratory System Function in Patients After Minimally Invasive Aortic Valve Replacement Surgery: A Case Control Study.

    Science.gov (United States)

    Stoliński, Jarosław; Musiał, Robert; Plicner, Dariusz; Andres, Janusz

    The aim of the study was to comparatively analyze respiratory system function after minimally invasive, through right minithoracotomy aortic valve replacement (RT-AVR) to conventional AVR. Analysis of 201 patients scheduled for RT-AVR and 316 for AVR between January 2010 and November 2013. Complications of the respiratory system and pulmonary functional status are presented. Complications of the respiratory system occurred in 16.8% of AVR and 11.0% of RT-AVR patients (P = 0.067). The rate of pleural effusions, thoracenteses, pneumonias, or phrenic nerve dysfunctions was not significantly different between groups. Perioperative mortality was 1.9% in AVR and 1.0% in RT-AVR (P = 0.417). Mechanical ventilation time after surgery was 9.7 ± 5.9 hours for AVR and 7.2 ± 3.2 hours for RT-AVR patients (P respiratory system complications. Spirometry examinations revealed that pulmonary functional status was more impaired after AVR in comparison with RT-AVR surgery.

  15. Long-term prognosis of mild functional tricuspid regurgitation after mitral valve replacement.

    Science.gov (United States)

    Gürsoy, Mete; Bakuy, Vedat; Hatemi, Ali Can; Bulut, Gülsüm; Kılıçkesmez, Kadriye; İnce, Nurhan; Küçükoğlu, Serdar

    2014-02-01

    Functional tricuspid regurgitation (FTR) is the most common type of tricuspid insufficiency and occurs approximately in 30% of patients with mitral valve disease. The major etiologic factor in the triggering of right ventricular dilation and thus causing functional tricuspid regurgitation, is pulmonary artery hypertension secondary to mitral valve disease. We aimed to analyze long-term outcomes of patients with mild tricuspid regurgitation at the time of mitral valve replacement. Sixty-six patients with mild tricuspid insufficiency who underwent mitral valve replacement were included in this observational retrospective study. Mean follow-up time was 8.3 ± 0.7 years. Patients whose tricuspid regurgitation remained unchanged or decreased following operation were enrolled to group 1 (n=32), patients whose tricuspid regurgitation increased were included to group 2 (n=34) and data were compared statistically with t-test, Mann-Whitney U, Chi-square and Fisher Exact test. Multiple regression analysis was performed to determine independent risk factors for FTR progression. REESULTS:Preoperatively female gender (p=0.02), body surface area (p=0.04), left atrium diameter (p=0.01), functional capacity (p=0.03), right ventricle diameter (p=0.04), and left ventricle mass index (p=0.04) were found to be statistically significant between groups. In the follow-up; functional capacity, grade of tricuspid insufficiency, pulmonary artery pressure, vena contracta width (ptricuspid annular plane systolic excursion index) (p=0.04), annulus diameter (p=0.02), right ventricle diameter (p=0.01), left ventricle mass index (p=0.05), and ejection fraction (p=0.02) were found to be statistically different between groups. In multiple logistic regression analysis; preoperative LA diameter (OR=5.05; 95% CI:1.49-17.12; p=0.009) and female gender (OR=10.93; 95% CI:1.77-67.31; p=0.01) were found as independent risk factors for FTR progression. This study revealed that mild FTR might advance to

  16. Species replacement by a nonnative salmonid alters ecosystem function by reducing prey subsidies that support riparian spiders

    Science.gov (United States)

    Benjamin, J.R.; Fausch, K.D.; Baxter, C.V.

    2011-01-01

    Replacement of a native species by a nonnative can have strong effects on ecosystem function, such as altering nutrient cycling or disturbance frequency. Replacements may cause shifts in ecosystem function because nonnatives establish at different biomass, or because they differ from native species in traits like foraging behavior. However, no studies have compared effects of wholesale replacement of a native by a nonnative species on subsidies that support consumers in adjacent habitats, nor quantified the magnitude of these effects. We examined whether streams invaded by nonnative brook trout (Salvelinus fontinalis) in two regions of the Rocky Mountains, USA, produced fewer emerging adult aquatic insects compared to paired streams with native cutthroat trout (Oncorhynchus clarkii), and whether riparian spiders that depend on these prey were less abundant along streams with lower total insect emergence. As predicted, emergence density was 36% lower from streams with the nonnative fish. Biomass of brook trout was higher than the cutthroat trout they replaced, but even after accounting for this difference, emergence was 24% lower from brook trout streams. More riparian spiders were counted along streams with greater total emergence across the water surface. Based on these results, we predicted that brook trout replacement would result in 6-20% fewer spiders in the two regions. When brook trout replace cutthroat trout, they reduce cross-habitat resource subsidies and alter ecosystem function in stream-riparian food webs, not only owing to increased biomass but also because traits apparently differ from native cutthroat trout. ?? 2011 Springer-Verlag.

  17. Improvement of a new rotation function for molecular replacement by designing new scoring functions and dynamic correlation coefficient

    International Nuclear Information System (INIS)

    Fan, Jiang; Wei, Ding

    2010-01-01

    A previously published new rotation function has been improved by using a dynamic correlation coefficient as well as two new scoring functions of relative entropy and mean-square-residues to make the rotation function more robust and independent of a specific set of weights for scoring and ranking. The previously described new rotation function calculates the rotation function of molecular replacement by matching the search model directly with the Patterson vector map. The signal-to-noise ratio for the correct match was increased by averaging all the matching peaks. Several matching scores were employed to evaluate the goodness of matching. These matching scores were then combined into a single total score by optimizing a set of weights using the linear regression method. It was found that there exists an optimal set of weights that can be applied to the global rotation search and the correct solution can be ranked in the top 100 or less. However, this set of optimal weights in general is dependent on the search models and the crystal structures with different space groups and cell parameters. In this work, we try to solve this problem by designing a dynamic correlation coefficient. It is shown that the dynamic correlation coefficient works for a variety of space groups and cell parameters in the global search of rotation function. We also introduce two new matching scores: relative entropy and mean-square-residues. Last but not least, we discussed a valid method for the optimization of the adjustable parameters for matching vectors. (condensed matter: structure, thermal and mechanical properties)

  18. The natural history of unexplained early poor function following total hip replacement.

    Science.gov (United States)

    Watson, Bruce S; Jenkins, Paul J; Ballantyne, James A

    2014-01-01

    The majority of patients experience a significant improvement in quality of life and function after total hip replacement (THR). It has recently been shown that age and good pre-operative function are the best predictors of postoperative function. When patients fail to achieve a satisfactory outcome, a cause is often identified. Where there is no identifiable cause, advice, follow-up and management is not clear. The aim of this study was to determine the long-term outcome of patients who had early poor function, but no identifiable cause. From a regional database, we identified 1,564 patients who underwent unilateral THR between 1998 and 2004 and who were without complication or subsequent bilateral procedure at six months. These patients were divided into two groups according to their Harris hip score (HHS) at this stage: group A consisted of 270 patients with a 'poor' result (HHS less than 70). Group B consisted of 1,294 patients with a 'good' or 'excellent' result (HHS 70 or above). The patients were reviewed at five years. One hundred and ten patients from group A and 980 from group B completed five-year follow-up without further identifiable complication. Those with poor or fair function at six months were at an increased risk of developing an identified complication by five years including dislocation (OR 5.7, 95% CI 1.8-18.2), deep infection (OR 9.8, 95%CI 2.9-37.7) and death (OR 1.6, 95% CI 1.1-2.3). There was a greater rate of revision in group A versus group B (OR 5.7, 95% CI 2.9-11). The overall function measured by the Harris hip score significantly improved in group A, but never reached that of those with good or excellent function at six months (HHS 76.2 versus 90.3, P < 0.001). Patients with poor function at six months, but no obvious cause, are at higher risk of developing complications by five years. This group may benefit from more regular arthroplasty review and intervention.

  19. Effects of androgen replacement therapy on cornea and tear function in men with idiopathic hypogonadotropic hypogonadism.

    Science.gov (United States)

    Gokce, Gokcen; Hurmeric, Volkan; Mumcuoglu, Tarkan; Ozge, Gokhan; Basaran, Yalcin; Unal, Hilmi Umut; Bolu, Erol; Mutlu, Fatih Mehmet

    2015-05-01

    Idiopathic hypogonadotropic hypogonadism (IHH) is an endocrine disorder defined with the presence of typical clinical signs and symptoms plus laboratory confirmation of serum testosterone (T) levels lower than 300 ng/dl. Androgen replacement therapy (ART) is the first-step treatment of male IHH. To date, no clinical trial, which investigates the changes on corneal structure and tear function, of systemic ART in men have been published. The objective of this study was to investigate the effects of ART on cornea and tear function in patients with IHH. This prospective, interventional study was conducted at the Gulhane Military Medical Academy, Ankara, Turkey, a tertiary referral military hospital. Thirty-four eyes of 17 men with IHH patients were evaluated with Schirmer I test, ultrasound pachymeter, applanation tonometer and confocal microscopy. A Testosterone compound (Sustanon® 250 mg) was administered by intramuscular injection in the course of a 3-week period to induce puberty, and human chorionic gonadotropin (Pregnyl® 5000 IU) was administered twice weekly for 3 months to induce fertility. The patients were re-evaluated at the third month of the treatment. Main Outcome Measures were Schirmer score, central corneal thickness (CCT), intraocular pressure (IOP), endothelial cell density, coefficient of variation and cell shape. Schirmer scores showed similar results after the treatment compared to pre-treatment levels (p = 0.14). There was no statistically significant difference in CCT and IOP compared to baseline data (p = 0.96, p = 0.73, respectively), and no significant differences were found in corneal endothelial cell density, percentage of cell size variability or hexagonality (p = 0.83, p = 0.58, p = 0.64, respectively). This is the first study that investigates the effects of ART on corneal structure and tear function in men. ART seems to have no short-term effects on corneal structure and tear function. Further publications of larger, long-term and

  20. Transcatheter Aortic Valve Replacement Results in Improvement of Pulmonary Function in Patients With Severe Aortic Stenosis.

    Science.gov (United States)

    Gilmore, Richard C; Thourani, Vinod H; Jensen, Hanna A; Condado, Jose; Binongo, José Nilo G; Sarin, Eric L; Devireddy, Chandan M; Leshnower, Bradley; Mavromatis, Kreton; Syed, Amjad; Guyton, Robert A; Block, Peter C; Simone, Amy; Keegan, Patricia; Stewart, James; Rajaei, Mohammad; Kaebnick, Brian; Lerakis, Stamatios; Babaliaros, Vasilis C

    2015-12-01

    Chronic obstructive pulmonary disease (COPD) has been identified as a risk factor for morbidity and mortality after transcatheter aortic valve replacement (TAVR). We hypothesized that a portion of pulmonary dysfunction in patients with severe aortic stenosis may be of cardiac origin, and has potential to improve after TAVR. A retrospective analysis was made of consecutive TAVR patients from April 2008 to October 2014. Of patients who had pulmonary function testing and serum B-type natriuretic peptide data available before and after TAVR, 58 were found to have COPD (26 mild, 14 moderate, and 18 severe). Baseline variables and operative outcomes were explored along with changes in pulmonary function. Multiple regression analyses were performed to adjust for preoperative left ventricular ejection fraction and glomerular filtration rate. Comparison of pulmonary function testing before and after the procedure among all COPD categories showed a 10% improvement in forced vital capacity (95% confidence interval: 4% to 17%) and a 12% improvement in forced expiratory volume in 1 second (95% confidence interval: 6% to 19%). There was a 29% decrease in B-type natriuretic peptide after TAVR (95% confidence interval: -40% to -16%). An improvement of at least one COPD severity category was observed in 27% of patients with mild COPD, 64% of patients with moderate COPD, and 50% of patients with severe COPD. There was no 30-day mortality in any patient group. In patients with severe aortic stenosis, TAVR is associated with a significant improvement of pulmonary function and B-type natriuretic peptide. After TAVR, the reduction in COPD severity was most evident in patients with moderate and severe pulmonary dysfunction. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Functional exercise after total hip replacement (FEATHER a randomised control trial

    Directory of Open Access Journals (Sweden)

    Monaghan Brenda

    2012-11-01

    Full Text Available Abstract Background Prolonged physical impairments in range of movement, postural stability and walking speed are commonly reported following total hip replacement (THR. It is unclear from the current body of evidence what kind of exercises should be performed to maximize patient function and quality of life. Methods/design This will be a single blind multi centre randomized control trial with two arms. Seventy subjects post primary total hip arthroplasty will be randomized into either an experimental group (n=35, or to a control group (n=35. The experimental group will attend a functional exercise class twice weekly for a six week period from week 12 to week 18 post surgery. The functional exercise group will follow a circuit based functional exercise class supervised by a chartered Physiotherapist. The control group will receive usual care. The principal investigator (BM will perform blinded outcome assessments on all patients using validated measures for pain, stiffness, and function using the Western Ontario and Mc Master Universities Osteoarthritis index (WOMAC. This is the primary outcome measurement tool. Secondary outcome measurements include Quality of life (SF-36, 6 min walk test, Visual Analogue Scale, and the Berg Balance score. The WOMAC score will be collated on day five post surgery and repeated at week twelve and week eighteen. All other measurements will be taken at week 12 and repeated at week eighteen. In addition a blinded radiologist will measure gluteus medius cross sectional area using real time ultrasound for all subjects at week 12 and at week 18 to determine if the functional exercise programme has any effect on muscle size. Discussion This randomised controlled trial will add to the body of evidence on the relationship between muscle size, functional ability, balance, quality of life and time post surgery in patients following total hip arthroplasty. The CONSORT guidelines will be followed to throughout. Ethical

  2. Left ventricular function improves after pulmonary valve replacement in patients with previous right ventricular outflow tract reconstruction and biventricular dysfunction.

    Science.gov (United States)

    Kane, Colin; Kogon, Brian; Pernetz, Maria; McConnell, Michael; Kirshbom, Paul; Rodby, Katherine; Book, Wendy M

    2011-01-01

    Congenital heart defects that have a component of right ventricular outflow tract obstruction, such as tetralogy of Fallot, are frequently palliated in childhood by disruption of the pulmonary valve. Although this can provide an initial improvement in quality of life, these patients are often left with severe pulmonary valve insufficiency. Over time, this insufficiency can lead to enlargement of the right ventricle and to the deterioration of right ventricular systolic and diastolic function. Pulmonary valve replacement in these patients decreases right ventricular volume overload and improves right ventricular performance. To date, few studies have examined the effects of pulmonary valve replacement on left ventricular function in patients with biventricular dysfunction. We sought to perform such an evaluation.Records of adult patients who had undergone pulmonary valve replacement from January 2003 through November 2006 were analyzed retrospectively. We reviewed preoperative and postoperative echocardiograms and calculated left ventricular function in 38 patients.In the entire cohort, the mean left ventricular ejection fraction increased by a mean of 0.07 after pulmonary valve replacement, which was a statistically significant change (P < 0.01). In patients with preoperative ejection fractions of less than 0.50, mean ejection fractions increased by 0.10.We conclude that pulmonary valve replacement in patients with biventricular dysfunction arising from severe pulmonary insufficiency and right ventricular enlargement can improve left ventricular function. Prospective studies are needed to verify this finding.

  3. Left Ventricular Function Improves after Pulmonary Valve Replacement in Patients with Previous Right Ventricular Outflow Tract Reconstruction and Biventricular Dysfunction

    Science.gov (United States)

    Kane, Colin; Kogon, Brian; Pernetz, Maria; McConnell, Michael; Kirshbom, Paul; Rodby, Katherine; Book, Wendy M.

    2011-01-01

    Congenital heart defects that have a component of right ventricular outflow tract obstruction, such as tetralogy of Fallot, are frequently palliated in childhood by disruption of the pulmonary valve. Although this can provide an initial improvement in quality of life, these patients are often left with severe pulmonary valve insufficiency. Over time, this insufficiency can lead to enlargement of the right ventricle and to the deterioration of right ventricular systolic and diastolic function. Pulmonary valve replacement in these patients decreases right ventricular volume overload and improves right ventricular performance. To date, few studies have examined the effects of pulmonary valve replacement on left ventricular function in patients with biventricular dysfunction. We sought to perform such an evaluation. Records of adult patients who had undergone pulmonary valve replacement from January 2003 through November 2006 were analyzed retrospectively. We reviewed preoperative and postoperative echocardiograms and calculated left ventricular function in 38 patients. In the entire cohort, the mean left ventricular ejection fraction increased by a mean of 0.07 after pulmonary valve replacement, which was a statistically significant change (P < 0.01). In patients with preoperative ejection fractions of less than 0.50, mean ejection fractions increased by 0.10. We conclude that pulmonary valve replacement in patients with biventricular dysfunction arising from severe pulmonary insufficiency and right ventricular enlargement can improve left ventricular function. Prospective studies are needed to verify this finding. PMID:21720459

  4. Essential Functional Modules for Pathogenic and Defensive Mechanisms in Candida albicans Infections

    OpenAIRE

    Wang, Yu-Chao; Tsai, I-Chun; Lin, Che; Hsieh, Wen-Ping; Lan, Chung-Yu; Chuang, Yung-Jen; Chen, Bor-Sen

    2014-01-01

    The clinical and biological significance of the study of fungal pathogen Candida albicans (C. albicans) has markedly increased. However, the explicit pathogenic and invasive mechanisms of such host-pathogen interactions have not yet been fully elucidated. Therefore, the essential functional modules involved in C. albicans-zebrafish interactions were investigated in this study. Adopting a systems biology approach, the early-stage and late-stage protein-protein interaction (PPI) networks for bo...

  5. Embryonic Cell Grafts in a Culture Model of Spinal Cord Lesion: Neuronal Relay Formation is Essential for Functional Regeneration

    Directory of Open Access Journals (Sweden)

    Anne Tscherter

    2016-09-01

    Full Text Available Presently there exists no cure for spinal cord injury. However, transplantation of embryonic tissue into spinal cord lesions resulted in axon outgrowth across the lesion site and some functional recovery, fostering hope for future stem cell therapies. Although in vivo evidence for functional recovery is given, the exact cellular mechanism of the graft support remains elusive: either the grafted cells provide a permissive environment for the host tissue to regenerate itself or the grafts actually integrate functionally into the host neuronal network reconnecting the separated spinal cord circuits. We tested the two hypotheses in an in vitro spinal cord lesion model that is based on propagation of activity between two rat organotypic spinal cord slices in culture. Transplantation of dissociated cells from E14 rat spinal cord or forebrain re-established the relay of activity over the lesion site and, thus, provoked functional regeneration. Combining patch-clamp recordings from transplanted cells with network activity measurements from the host tissue on multi-electrode arrays we here show that neurons differentiate from the grafted cells and integrate into the host circuits. Optogenetic silencing of neurons developed from transplanted embryonic mouse forebrain cells provides clear evidence that they replace the lost neuronal connections to relay and synchronize activity between the separated spinal cord circuits. In contrast, transplantation of neurospheres induced neither the differentiation of mature neurons from the grafts nor an improvement of functional regeneration. Together these findings suggest, that the formation of neuronal relays from grafted embryonic cells is essential to re-connect segregated spinal cord circuits.

  6. Function of the Respiratory System in Elderly Patients After Aortic Valve Replacement.

    Science.gov (United States)

    Stoliński, Jarosław; Plicner, Dariusz; Gawęda, Bogusław; Musiał, Robert; Fijorek, Kamil; Wąsowicz, Marcin; Andres, Janusz; Kapelak, Bogusław

    2016-10-01

    To compare the function of the respiratory system after aortic valve replacement through median sternotomy (AVR) or the minimally invasive right anterior minithoracotomy (RAT-AVR) approach among elderly (aged≥75 years) patients. Observational cohort study. University hospital. The study included 65 elderly patients scheduled for RAT-AVR and 82 for standard AVR. Pulmonary function tests (PFT) were performed preoperatively, 1 week, 1 month, and 3 months after surgery. In addition, respiratory complications were analyzed. Respiratory complications occurred in 12.3% of patients in the RAT-AVR group and 18.3% of patients in the AVR group (p = 0.445). Mechanical ventilation time in the intensive care unit was 7.7±3.6 hours for RAT-AVR patients and 9.7±5.4 hours for AVR patients (p = 0.003). Most PFT were worse in the AVR group than in the RAT-AVR group when performed 1 week after surgery. After 1 month, forced expiratory volume in the first second, vital capacity, and total lung capacity differed significantly in favor of the RAT-AVR group (p = 0.002, p<0.001, and p = 0.001, respectively). After 3 months, the PFT parameters still had not returned to preoperative values, but the differences were no longer significant between the RAT-AVR and AVR groups. The multivariable median regression analysis demonstrated that RAT-AVR surgery was a key factor in a patient's higher postoperative PFT parameter values. RAT-AVR surgery resulted in shorter postoperative mechanical ventilation time and improved the recovery of pulmonary function in elderly patients, but it did not reduce the incidence of pulmonary complications when compared with surgery performed through a median sternotomy. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison′ s disease with primary hypothyroidism

    Directory of Open Access Journals (Sweden)

    Jaya Prakash Sahoo

    2016-01-01

    Full Text Available Background: Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab titer in Addison's disease with primary hypothyroidism. Materials and Methods: This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (22 pmol/L and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical was defined as high thyroid stimulating hormone (TSH with/without low free thyroxine (fT4. TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Results: Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. Conclusions: The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations.

  8. Hemodynamic function of the standard St. Jude bileaflet disc valve has no clinical impact 10 years after aortic valve replacement

    DEFF Research Database (Denmark)

    Lund, Ole; Dorup, Inge; Emmertsen, Kristian

    2005-01-01

    OBJECTIVES: Size mismatch and impaired left ventricular function have been shown to determine the hemodynamic function of the standard St. Jude bileaflet disc valve early after aortic valve replacement (AVR). We aimed to analyse St. Jude valve hemodynamic function and its clinical impact in the s......OBJECTIVES: Size mismatch and impaired left ventricular function have been shown to determine the hemodynamic function of the standard St. Jude bileaflet disc valve early after aortic valve replacement (AVR). We aimed to analyse St. Jude valve hemodynamic function and its clinical impact......Hg. In a multilinear regression analysis GOA indexed for LVEDD, hypertension, and LVEF were independently related to peak gradient. CONCLUSION: High gradients of the standard St. Jude bileaflet disc valve 10 years after AVR was primarily related to systemic hypertension and mismatch between valve and left ventricular...

  9. Essential Functional Modules for Pathogenic and Defensive Mechanisms in Candida albicans Infections

    Directory of Open Access Journals (Sweden)

    Yu-Chao Wang

    2014-01-01

    Full Text Available The clinical and biological significance of the study of fungal pathogen Candida albicans (C. albicans has markedly increased. However, the explicit pathogenic and invasive mechanisms of such host-pathogen interactions have not yet been fully elucidated. Therefore, the essential functional modules involved in C. albicans-zebrafish interactions were investigated in this study. Adopting a systems biology approach, the early-stage and late-stage protein-protein interaction (PPI networks for both C. albicans and zebrafish were constructed. By comparing PPI networks at the early and late stages of the infection process, several critical functional modules were identified in both pathogenic and defensive mechanisms. Functional modules in C. albicans, like those involved in hyphal morphogenesis, ion and small molecule transport, protein secretion, and shifts in carbon utilization, were seen to play important roles in pathogen invasion and damage caused to host cells. Moreover, the functional modules in zebrafish, such as those involved in immune response, apoptosis mechanisms, ion transport, protein secretion, and hemostasis-related processes, were found to be significant as defensive mechanisms during C. albicans infection. The essential functional modules thus determined could provide insights into the molecular mechanisms of host-pathogen interactions during the infection process and thereby devise potential therapeutic strategies to treat C. albicans infection.

  10. Essential functional modules for pathogenic and defensive mechanisms in Candida albicans infections.

    Science.gov (United States)

    Wang, Yu-Chao; Tsai, I-Chun; Lin, Che; Hsieh, Wen-Ping; Lan, Chung-Yu; Chuang, Yung-Jen; Chen, Bor-Sen

    2014-01-01

    The clinical and biological significance of the study of fungal pathogen Candida albicans (C. albicans) has markedly increased. However, the explicit pathogenic and invasive mechanisms of such host-pathogen interactions have not yet been fully elucidated. Therefore, the essential functional modules involved in C. albicans-zebrafish interactions were investigated in this study. Adopting a systems biology approach, the early-stage and late-stage protein-protein interaction (PPI) networks for both C. albicans and zebrafish were constructed. By comparing PPI networks at the early and late stages of the infection process, several critical functional modules were identified in both pathogenic and defensive mechanisms. Functional modules in C. albicans, like those involved in hyphal morphogenesis, ion and small molecule transport, protein secretion, and shifts in carbon utilization, were seen to play important roles in pathogen invasion and damage caused to host cells. Moreover, the functional modules in zebrafish, such as those involved in immune response, apoptosis mechanisms, ion transport, protein secretion, and hemostasis-related processes, were found to be significant as defensive mechanisms during C. albicans infection. The essential functional modules thus determined could provide insights into the molecular mechanisms of host-pathogen interactions during the infection process and thereby devise potential therapeutic strategies to treat C. albicans infection.

  11. A second essential function of the Est1-binding arm of yeast telomerase RNA.

    Science.gov (United States)

    Lebo, Kevin J; Niederer, Rachel O; Zappulla, David C

    2015-05-01

    The enzymatic ribonucleoprotein telomerase maintains telomeres in many eukaryotes, including humans, and plays a central role in aging and cancer. Saccharomyces cerevisiae telomerase RNA, TLC1, is a flexible scaffold that tethers telomerase holoenzyme protein subunits to the complex. Here we test the hypothesis that a lengthy conserved region of the Est1-binding TLC1 arm contributes more than simply Est1-binding function. We separated Est1 binding from potential other functions by tethering TLC1 to Est1 via a heterologous RNA-protein binding module. We find that Est1-tethering rescues in vivo function of telomerase RNA alleles missing nucleotides specifically required for Est1 binding, but not those missing the entire conserved region. Notably, however, telomerase function is restored for this condition by expressing the arm of TLC1 in trans. Mutational analysis shows that the Second Essential Est1-arm Domain (SEED) maps to an internal loop of the arm, which SHAPE chemical mapping and 3D modeling suggest could be regulated by conformational change. Finally, we find that the SEED has an essential, Est1-independent role in telomerase function after telomerase recruitment to the telomere. The SEED may be required for establishing telomere extendibility or promoting telomerase RNP holoenzyme activity. © 2015 Lebo et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  12. Functional mapping of Saccharomyces cerevisiae Prp45 identifies the SNW domain as essential for viability.

    Science.gov (United States)

    Martinkova, Katerina; Lebduska, Pavel; Skruzny, Michal; Folk, Petr; Puta, Frantisek

    2002-10-01

    The essential gene product Prp45 (379 aa) of Saccharomyces cerevisiae is a highly conserved, but N-terminally abridged, ortholog of the human transcriptional coactivator SKIP, which is involved in TGFbeta, Notch, and steroid hormone signaling. We used a diploid strain harboring PRP45 deletion, which is inviable in the haploid, to test for complementation with the truncated versions of Prp45. The N-terminal half of the protein (aa 1 to 190), denoted as the SNW domain, was found sufficient to support the essential function. Interestingly, substituting the SNW motif itself with AAA was compatible with viability. GFP-tagged Prp45 was localized in nuclear "speckles" over a diffuse nuclear background. We further found that Prp45 activated the transcription of a reporter gene in S. cerevisiae when targeted to DNA. The observed effect relied in part upon the presence of conserved helical repeats and upon the highly charged C-terminal domain (pI = 11.3). Prp45, which lacks most of the binding motifs of the human ortholog, and whose N-terminal half is sufficient for supporting the growth of prp45 cells, might be helpful in elucidating the essential function of SNW/SKIP proteins.

  13. OPTIMAL IMPROVEMENT IN FUNCTION AFTER TOTAL HIP AND KNEE REPLACEMENT: HOW DEEP DO YOU KNOW YOUR PATIENT’S MIND?

    Science.gov (United States)

    De Caro, M F; Vicenti, G; Abate, A; Picca, G; Leoncini, V; Lomuscio, M; Casalino, A; Solarino, G; Moretti, B

    2015-01-01

    Osteoarthritis (OA) of the hip and knee causes pain and loss of joint mobility, leading to limitations in physical function. When conservative treatment fails total hip and knee replacement is a cost-effective surgical option. Patients have high expectations regarding functional outcome after these procedures. If such expectations are not met, they may still be dissatisfied with the outcome of a technically successful procedure. Recently, numerous studies reported that psychological factors can influence the outcome of total knee replacement (tkr) and total hip artrhoplasty with total hip replacement (thr). We conducted a prospective study on a consecutive sample of 280 patients affected by hip or knee OA who underwent total joint replacement. At patients’ admission, Harris Hip Score (HHS) and Knee Society Score (KSS) were used to assess pain and function. Furthermore, SF-36, Mini-Mental Status Examination (MMSE), Symptom Checklist-90-R (SCL-90-R), Coping Orientation to Problems Experienced (BRIEF-COPE) and the Amsterdam Preoperative Anxiety and Information Scale (APAIS) were administered. Patients had clinical and radio graphical follow up at 1, 3 and 6 months post-operatively. The HHS and KSS values before surgery showed a linear correlation with both SCL-90-R and MMSE. None of the investigated variables influenced post-operative HHS and KSS scores; however, the improvement of functional scores resulted conditioned by SCL-90-R values, VAS score, schooling and MMSE. Psychological factors and mental status in primary total hip and knee replacement can affect outcome and patient satisfaction. Strategies focused on identification and facing of these conditions must be considered to improve outcome of total replacement.

  14. Functional analysis of the molecular interactions of TATA box-containing genes and essential genes.

    Science.gov (United States)

    Bae, Sang-Hun; Han, Hyun Wook; Moon, Jisook

    2015-01-01

    Genes can be divided into TATA-containing genes and TATA-less genes according to the presence of TATA box elements at promoter regions. TATA-containing genes tend to be stress-responsive, whereas many TATA-less genes are known to be related to cell growth or "housekeeping" functions. In a previous study, we demonstrated that there are striking differences among four gene sets defined by the presence of TATA box (TATA-containing) and essentiality (TATA-less) with respect to number of associated transcription factors, amino acid usage, and functional annotation. Extending this research in yeast, we identified KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways that are statistically enriched in TATA-containing or TATA-less genes and evaluated the possibility that the enriched pathways are related to stress or growth as reflected by the individual functions of the genes involved. According to their enrichment for either of these two gene sets, we sorted KEGG pathways into TATA-containing-gene-enriched pathways (TEPs) and essential-gene-enriched pathways (EEPs). As expected, genes in TEPs and EEPs exhibited opposite results in terms of functional category, transcriptional regulation, codon adaptation index, and network properties, suggesting the possibility that the bipolar patterns in these pathways also contribute to the regulation of the stress response and to cell survival. Our findings provide the novel insight that significant enrichment of TATA-binding or TATA-less genes defines pathways as stress-responsive or growth-related.

  15. Quantitative liver functions in Turner syndrome with and without hormone replacement therapy

    DEFF Research Database (Denmark)

    Gravholt, Claus Højbjerg; Poulsen, Henrik Enghusen; Ott, Peter

    2007-01-01

    Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes....

  16. Renal function predicts long-term outcome on enzyme replacement therapy in patients with Fabry disease.

    Science.gov (United States)

    Lenders, Malte; Schmitz, Boris; Stypmann, Jörg; Duning, Thomas; Brand, Stefan-Martin; Kurschat, Christine; Brand, Eva

    2017-12-01

    Renal and cardiac involvement is responsible for substantial morbidity and mortality in Fabry disease (FD). We analysed the incidence of FD-related renal, cardiac and neurologic end points in patients with FD on long-term enzyme replacement therapy (ERT). A retrospective analysis of prospectively collected data from two German FD centres was performed. The impact of renal and cardiac function at ERT-naïve baseline on end point development despite ERT was analysed. Fifty-four patients (28 females) receiving ERT (mean 81 ± 21 months) were investigated. Forty per cent of patients were diagnosed with clinical end points before ERT initiation and 50% of patients on ERT developed new clinical end points. In patients initially diagnosed with an end point before ERT initiation, the risk for an additional end point on ERT was increased {hazard ratio [HR] 3.83 [95% confidence interval (CI) 1.61-9.08]; P = 0.0023}. A decreased glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 in ERT-naïve patients at baseline was associated with an increased risk for cardiovascular end points [HR 3.59 (95% CI 1.15-11.18); P = 0.0273] as well as for combined renal, cardiac and neurologic end points on ERT [HR 4.77 (95% CI 1.93-11.81); P = 0.0007]. In patients with normal kidney function, left ventricular hypertrophy at baseline predicted a decreased end point-free survival [HR 6.90 (95% CI 2.04-23.27); P = 0.0018]. The risk to develop an end point was independent of sex. In addition to age, even moderately impaired renal function determines FD progression on ERT. In patients with FD, renal and cardiac protection is warranted to prevent patients from deleterious manifestations of the disease. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  17. Quantitative liver functions in Turner syndrome with and without hormone replacement therapy

    DEFF Research Database (Denmark)

    Gravholt, Claus Højbjerg; Poulsen, Henrik Enghusen; Ott, Peter

    2007-01-01

    Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes.......Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes....

  18. The hierarchy of essential CANDU reactor control functions in a distributed system

    International Nuclear Information System (INIS)

    Mercier, P.

    1980-01-01

    Control functions in CANDU nuclear generating stations are programmed within two centralized and redundant minicomputers while safety functions are covered by conventional analog systems. This set-up is a product of standards, economic and technical considerations which are now being modified by the maturing of microprocessors, the progress in digital communications and the development of mathematical process models. Starting from the control and safety systems installed in Gentilly-2, this paper analyses trends that will affect the implementation of essential control functions within a distributed system. In particular, it emphasizes the characteristics of future software systems that must be built-in in order to comply with important operational requirements of nuclear generating stations. (auth) [fr

  19. Levothyroxine replacement in hypothyroid humans reduces myocardial lipid load and improves cardiac function.

    Science.gov (United States)

    Scherer, Thomas; Wolf, Peter; Winhofer, Yvonne; Duan, Heying; Einwallner, Elisa; Gessl, Alois; Luger, Anton; Trattnig, Siegfried; Hoffmann, Martha; Niessner, Alexander; Baumgartner-Parzer, Sabina; Krššák, Martin; Krebs, Michael

    2014-11-01

    Hypothyroidism is a common endocrine disorder frequently accompanied by alterations in lipid metabolism, such as hypercholesterolemia and high circulating triglycerides, both risk factors for nonischemic cardiomyopathy. Rodent studies suggest that the hypothyroid state promotes cardiac lipid retention by increasing lipid uptake into cardiomyocytes while reducing fatty acid oxidation. Furthermore, increased cardiac lipid load has been linked to cardiac dysfunction. Dyslipidemia and hypothyroidism frequently coexist; thus, we hypothesized that overt hypothyroidism causes cardiac lipid deposition and ultimately cardiac dysfunction. An interventional prospective study with balanced within-subject comparison. PARTICIPANTS/SETTING/INTERVENTION: Ten patients recruited at an academic center, who underwent a thyroidectomy due to differentiated thyroid carcinoma, were examined 4 weeks postoperatively in the overtly hypothyroid state, right before radioiodine therapy, and 6-8 weeks after initiation of levothyroxine replacement. We measured cardiac lipid content and function in vivo before and after levothyroxine treatment using electrocardiogram-gated (1)H-magnetic resonance spectroscopy and imaging. Levothyroxine therapy reduced cardiac lipid content in nine of the 10 patients (0.35 ± 0.09 vs 0.22 ± 0.06 % water signal; P = .008; n = 10) and improved cardiac index (2 ± 0.2 vs 2.4 ± 0.1 L/min/m(2); P = .047) when comparing the hypothyroid with the euthyroid state, independent of changes in liver fat content (7.5 ± 3.2 vs 7.1 ± 2.6% magnetic resonance spectroscopy signal; P = .60) or body weight. Here we show that levothyroxine treatment reduces lipid accumulation in the heart and increases cardiac output in overtly hypothyroid patients. These results could in part explain the increased risk of death and heart failure in hypothyroid patients.

  20. Q192R Paraoxonase (PON)1 Polymorphism, Insulin Sensitivity, and Endothelial Function in Essential Hypertensive Men.

    Science.gov (United States)

    Dell'Omo, Giulia; Penno, Giuseppe; Pucci, Laura; Lucchesi, Daniela; Del Prato, Stefano; Pedrinelli, Roberto

    2014-01-01

    Essential hypertension is characterized by increased reactive oxygen species (ROS) generation harmful for insulin sensitivity and nitric oxide (NO)-mediated vasomotor function, a noxious effect that paraoxonase (PON)1, an antioxidant circulating high-density lipoprotein (HDL)-bound esterase, may counteract. The PON1 gene contains several polymorphisms including a glutamine (Q) to arginine (R) transition at position 192 encoding circulating allozymes with higher antioxidant activity that might influence both parameters. Q192R was determined by polymerase chain reaction in 72 never-treated, glucose-tolerant, uncomplicated essential hypertensive men. Insulin sensitivity was assessed by homeostasis model assessment (HOMA) and endothelial function by forearm vasodilation (strain-gage venous plethysmography) to intra-arterial acetylcholine (ACH) with sodium nitroprusside (NIP) as a NO-independent control. Additional evaluation variables included 24-hour blood pressure (BP), lipids, BMI, smoking status, and metabolic syndrome (MetS) by Adult Treatment Panel (ATP)-III criteria. R192 was considered as the rare allele, and its associations analyzed by dominant models (Q/Q vs. Q/R + R/R). Genotype frequencies were consistent with the Hardy-Weinberg equilibrium. HOMA was lower and insulin resistance (the upper fourth of HOMA values distribution) less prevalent in Q/R + R/R carriers in whom ACH-mediated vasodilatation was greater and endothelial dysfunction (the bottom fourth of ACH(AUC) values distribution) less frequent than in Q/Q homozygotes. Q192R polymorphism and MetS were unrelated parameters despite their common association with insulin resistance. 24-hour BP, BMI, lipids, and smoking habits were homogeneously distributed across genotypes. Q192R polymorphism associates differentially with insulin sensitivity and endothelial function in essential hypertensive men.

  1. Q192R Paraoxonase (PON)1 Polymorphism, Insulin Sensitivity, and Endothelial Function in Essential Hypertensive Men

    Science.gov (United States)

    Dell’Omo, Giulia; Penno, Giuseppe; Pucci, Laura; Lucchesi, Daniela; Prato, Stefano Del; Pedrinelli, Roberto

    2014-01-01

    AIMS Essential hypertension is characterized by increased reactive oxygen species (ROS) generation harmful for insulin sensitivity and nitric oxide (NO)-mediated vasomotor function, a noxious effect that paraoxonase (PON)1, an antioxidant circulating high-density lipoprotein (HDL)-bound esterase, may counteract. The PON1 gene contains several polymorphisms including a glutamine (Q) to arginine (R) transition at position 192 encoding circulating allozymes with higher antioxidant activity that might influence both parameters. METHODS Q192R was determined by polymerase chain reaction in 72 never-treated, glucose-tolerant, uncomplicated essential hypertensive men. Insulin sensitivity was assessed by homeostasis model assessment (HOMA) and endothelial function by forearm vasodilation (strain-gage venous plethysmography) to intra-arterial acetylcholine (ACH) with sodium nitroprusside (NIP) as a NO-independent control. Additional evaluation variables included 24-hour blood pressure (BP), lipids, BMI, smoking status, and metabolic syndrome (MetS) by Adult Treatment Panel (ATP)-III criteria. R192 was considered as the rare allele, and its associations analyzed by dominant models (Q/Q vs. Q/R + R/R). RESULTS Genotype frequencies were consistent with the Hardy–Weinberg equilibrium. HOMA was lower and insulin resistance (the upper fourth of HOMA values distribution) less prevalent in Q/R + R/R carriers in whom ACH-mediated vasodilatation was greater and endothelial dysfunction (the bottom fourth of ACHAUC values distribution) less frequent than in Q/Q homozygotes. Q192R polymorphism and MetS were unrelated parameters despite their common association with insulin resistance. 24-hour BP, BMI, lipids, and smoking habits were homogeneously distributed across genotypes. CONCLUSIONS Q192R polymorphism associates differentially with insulin sensitivity and endothelial function in essential hypertensive men. PMID:25089090

  2. The essential function of B. subtilis RNase III is to silence foreign toxin genes.

    Directory of Open Access Journals (Sweden)

    Sylvain Durand

    Full Text Available RNase III-related enzymes play key roles in cleaving double-stranded RNA in many biological systems. Among the best-known are RNase III itself, involved in ribosomal RNA maturation and mRNA turnover in bacteria, and Drosha and Dicer, which play critical roles in the production of micro (mi-RNAs and small interfering (si-RNAs in eukaryotes. Although RNase III has important cellular functions in bacteria, its gene is generally not essential, with the remarkable exception of that of Bacillus subtilis. Here we show that the essential role of RNase III in this organism is to protect it from the expression of toxin genes borne by two prophages, Skin and SPβ, through antisense RNA. Thus, while a growing number of organisms that use RNase III or its homologs as part of a viral defense mechanism, B. subtilis requires RNase III for viral accommodation to the point where the presence of the enzyme is essential for cell survival. We identify txpA and yonT as the two toxin-encoding mRNAs of Skin and SPβ that are sensitive to RNase III. We further explore the mechanism of RNase III-mediated decay of the txpA mRNA when paired to its antisense RNA RatA, both in vivo and in vitro.

  3. Cognitive Stimulation is Essential to Maintain and/or Improve the Cognitive Function of the Elderly

    Directory of Open Access Journals (Sweden)

    Telma Filipa Mendes Ramos

    2017-04-01

    Full Text Available Introduction: Cognitive stimulation is essential to maintain and / or improve the cognitive function of the elderly. Objectives: This study aimed to evaluate the impact of the application of a Cognitive Stimulation Program on the maintenance or improvement of the cognitive function of the elderly at the levels of orientation, memory, calculation and language. It was also intended to evaluate complementary measures of the impact of the intervention program, name- ly on the quality of life, depressive symptoms, in the eight cognitive domains, executive function, visuospatial capacity, memory, attention, concentration and working memory, language and orientation. Method: The program was performed in 14 sessions for seven weeks, with pre-and post-test measurements. The final sample consisted of seven elderly men, four men and three women aged between 68-89 years (80.29 ± 8.83 years, who responded to the following measures: Montreal Cognitive Assessment (MoCA, Quality of life (IAQdV-8, Geriatric De- pression Scale (GDS-15 and Cognitive Decline Test (6-CIT. Results: The post-test cognitive decline in relation to the pre-test decreased significantly (6_CIT, with an improvement in the cognitive function of the elderly. The improvement of some indicators of cognitive function is positively correlated with the self-perception of quality of life with negatively depressive symptomatology. Conclusions: The administration of Cognitive Stimulation Programs contributes to an im- provement of the cognitive function in the elderly and an increase in the quality of life.

  4. Organization, function and substrates of the essential Clp protease system in plastids.

    Science.gov (United States)

    Nishimura, Kenji; van Wijk, Klaas J

    2015-09-01

    Intra-plastid proteolysis is essential in plastid biogenesis, differentiation and plastid protein homeostasis (proteostasis). We provide a comprehensive review of the Clp protease system present in all plastid types and we draw lessons from structural and functional information of bacterial Clp systems. The Clp system plays a central role in plastid development and function, through selective removal of miss-folded, aggregated, or otherwise unwanted proteins. The Clp system consists of a tetradecameric proteolytic core with catalytically active ClpP and inactive ClpR subunits, hexameric ATP-dependent chaperones (ClpC,D) and adaptor protein(s) (ClpS1) enhancing delivery of subsets of substrates. Many structural and functional features of the plastid Clp system are now understood though extensive reverse genetics analysis combined with biochemical analysis, as well as large scale quantitative proteomics for loss-of-function mutants of Clp core, chaperone and ClpS1 subunits. Evolutionary diversification of Clp system across non-photosynthetic and photosynthetic prokaryotes and organelles is illustrated. Multiple substrates have been suggested based on their direct interaction with the ClpS1 adaptor or screening of different loss-of-function protease mutants. The main challenge is now to determine degradation signals (degrons) in Clp substrates and substrate delivery mechanisms, as well as functional interactions of Clp with other plastid proteases. This article is part of a Special Issue entitled: Chloroplast Biogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance

    Science.gov (United States)

    van Oers, Johanna M. M.; Roa, Sergio; Werling, Uwe; Liu, Yiyong; Genschel, Jochen; Sellers, Rani S.; Modrich, Paul; Scharff, Matthew D.; Edelmann, Winfried

    2010-01-01

    The DNA mismatch repair protein PMS2 was recently found to encode a novel endonuclease activity. To determine the biological functions of this activity in mammals, we generated endonuclease-deficient Pms2E702K knock-in mice. Pms2EK/EK mice displayed increased genomic mutation rates and a strong cancer predisposition. In addition, class switch recombination, but not somatic hypermutation, was impaired in Pms2EK/EK B cells, indicating a specific role in Ig diversity. In contrast to Pms2−/− mice, Pms2EK/EK male mice were fertile, indicating that this activity is dispensable in spermatogenesis. Therefore, the PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance and tumor suppression. PMID:20624957

  6. Increased plasmid copy number is essential for Yersinia T3SS function and virulence.

    Science.gov (United States)

    Wang, He; Avican, Kemal; Fahlgren, Anna; Erttmann, Saskia F; Nuss, Aaron M; Dersch, Petra; Fallman, Maria; Edgren, Tomas; Wolf-Watz, Hans

    2016-07-29

    Pathogenic bacteria have evolved numerous virulence mechanisms that are essential for establishing infections. The enterobacterium Yersinia uses a type III secretion system (T3SS) encoded by a 70-kilobase, low-copy, IncFII-class virulence plasmid. We report a novel virulence strategy in Y. pseudotuberculosis in which this pathogen up-regulates the plasmid copy number during infection. We found that an increased dose of plasmid-encoded genes is indispensable for virulence and substantially elevates the expression and function of the T3SS. Remarkably, we observed direct, tight coupling between plasmid replication and T3SS function. This regulatory pathway provides a framework for further exploration of the environmental sensing mechanisms of pathogenic bacteria. Copyright © 2016, American Association for the Advancement of Science.

  7. NF-κB Essential Modulator (NEMO) Is Critical for Thyroid Function*

    Science.gov (United States)

    Reale, Carla; Iervolino, Anna; Scudiero, Ivan; Ferravante, Angela; D'Andrea, Luca Egildo; Mazzone, Pellegrino; Zotti, Tiziana; Leonardi, Antonio; Roberto, Luca; Zannini, Mariastella; de Cristofaro, Tiziana; Shanmugakonar, Muralitharan; Capasso, Giovambattista; Pasparakis, Manolis; Vito, Pasquale; Stilo, Romania

    2016-01-01

    The I-κB kinase (IKK) subunit NEMO/IKKγ (NEMO) is an adapter molecule that is critical for canonical activation of NF-κB, a pleiotropic transcription factor controlling immunity, differentiation, cell growth, tumorigenesis, and apoptosis. To explore the functional role of canonical NF-κB signaling in thyroid gland differentiation and function, we have generated a murine strain bearing a genetic deletion of the NEMO locus in thyroid. Here we show that thyrocyte-specific NEMO knock-out mice gradually develop hypothyroidism after birth, which leads to reduced body weight and shortened life span. Histological and molecular analysis indicate that absence of NEMO in thyrocytes results in a dramatic loss of the thyroid gland cellularity, associated with down-regulation of thyroid differentiation markers and ongoing apoptosis. Thus, NEMO-dependent signaling is essential for normal thyroid physiology. PMID:26786105

  8. New genes often acquire male-specific functions but rarely become essential in Drosophila.

    Science.gov (United States)

    Kondo, Shu; Vedanayagam, Jeffrey; Mohammed, Jaaved; Eizadshenass, Sogol; Kan, Lijuan; Pang, Nan; Aradhya, Rajaguru; Siepel, Adam; Steinhauer, Josefa; Lai, Eric C

    2017-09-15

    Relatively little is known about the in vivo functions of newly emerging genes, especially in metazoans. Although prior RNAi studies reported prevalent lethality among young gene knockdowns, our phylogenomic analyses reveal that young Drosophila genes are frequently restricted to the nonessential male reproductive system. We performed large-scale CRISPR/Cas9 mutagenesis of "conserved, essential" and "young, RNAi-lethal" genes and broadly confirmed the lethality of the former but the viability of the latter. Nevertheless, certain young gene mutants exhibit defective spermatogenesis and/or male sterility. Moreover, we detected widespread signatures of positive selection on young male-biased genes. Thus, young genes have a preferential impact on male reproductive system function. © 2017 Kondo et al.; Published by Cold Spring Harbor Laboratory Press.

  9. Essential role of EBF1 in the generation and function of distinct mature B cell types.

    Science.gov (United States)

    Vilagos, Bojan; Hoffmann, Mareike; Souabni, Abdallah; Sun, Qiong; Werner, Barbara; Medvedovic, Jasna; Bilic, Ivan; Minnich, Martina; Axelsson, Elin; Jaritz, Markus; Busslinger, Meinrad

    2012-04-09

    The transcription factor EBF1 is essential for lineage specification in early B cell development. In this study, we demonstrate by conditional mutagenesis that EBF1 is required for B cell commitment, pro-B cell development, and subsequent transition to the pre-B cell stage. Later in B cell development, EBF1 was essential for the generation and maintenance of several mature B cell types. Marginal zone and B-1 B cells were lost, whereas follicular (FO) and germinal center (GC) B cells were reduced in the absence of EBF1. Activation of the B cell receptor resulted in impaired intracellular signaling, proliferation and survival of EBF1-deficient FO B cells. Immune responses were severely reduced upon Ebf1 inactivation, as GCs were formed but not maintained. ChIP- and RNA-sequencing of FO B cells identified EBF1-activated genes that encode receptors, signal transducers, and transcriptional regulators implicated in B cell signaling. Notably, ectopic expression of EBF1 efficiently induced the development of B-1 cells at the expense of conventional B cells. These gain- and loss-of-function analyses uncovered novel important functions of EBF1 in controlling B cell immunity.

  10. The systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmission

    KAUST Repository

    Tewari, Rita

    2010-10-21

    Although eukaryotic protein kinases (ePKs) contribute to many cellular processes, only three Plasmodium falciparum ePKs have thus far been identified as essential for parasite asexual blood stage development. To identify pathways essential for parasite transmission between their mammalian host and mosquito vector, we undertook a systematic functional analysis of ePKs in the genetically tractable rodent parasite Plasmodium berghei. Modeling domain signatures of conventional ePKs identified 66 putative Plasmodium ePKs. Kinomes are highly conserved between Plasmodium species. Using reverse genetics, we show that 23 ePKs are redundant for asexual erythrocytic parasite development in mice. Phenotyping mutants at four life cycle stages in Anopheles stephensi mosquitoes revealed functional clusters of kinases required for sexual development and sporogony. Roles for a putative SR protein kinase (SRPK) in microgamete formation, a conserved regulator of clathrin uncoating (GAK) in ookinete formation, and a likely regulator of energy metabolism (SNF1/KIN) in sporozoite development were identified. 2010 Elsevier Inc.

  11. Plasmodium strain determines dendritic cell function essential for survival from malaria.

    Directory of Open Access Journals (Sweden)

    Michelle N Wykes

    2007-07-01

    Full Text Available The severity of malaria can range from asymptomatic to lethal infections involving severe anaemia and cerebral disease. However, the molecular and cellular factors responsible for these differences in disease severity are poorly understood. Identifying the factors that mediate virulence will contribute to developing antiparasitic immune responses. Since immunity is initiated by dendritic cells (DCs, we compared their phenotype and function following infection with either a nonlethal or lethal strain of the rodent parasite, Plasmodium yoelii, to identify their contribution to disease severity. DCs from nonlethal infections were fully functional and capable of secreting cytokines and stimulating T cells. In contrast, DCs from lethal infections were not functional. We then transferred DCs from mice with nonlethal infections to mice given lethal infections and showed that these DCs mediated control of parasitemia and survival. IL-12 was necessary for survival. To our knowledge, our studies have shown for the first time that during a malaria infection, DC function is essential for survival. More importantly, the functions of these DCs are determined by the strain of parasite. Our studies may explain, in part, why natural malaria infections may have different outcomes.

  12. The planned replacement of a functioning control system on the CERN 28 GEV accelerator

    International Nuclear Information System (INIS)

    Carpenter, B.E.; Daneels, A.; Perriollat, F.

    1979-01-01

    The subject is discussed under the following headings: the accelerators (in the 28 GeV accelerator complex) and the old control system; goals of the new control system; constraints (involved in planning a replacement for the control system); a pilot project; major software issues in the system design; portability; parallelism; transition; conclusion. (U.K.)

  13. Structure–function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination

    Science.gov (United States)

    Zhao, Liang; Ng, Ee Ting; Davidson, Tara-Lynne; Longmuss, Enya; Urschitz, Johann; Elston, Marlee; Moisyadi, Stefan; Bowles, Josephine; Koopman, Peter

    2014-01-01

    The mammalian sex-determining factor SRY comprises a conserved high-mobility group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is essential for male sex determination. To dissect the molecular functions of this domain, we generated a series of Sry mutants, and studied their biochemical properties in cell lines and transgenic mouse embryos. Sry protein lacking the polyQ domain was unstable, due to proteasomal degradation. Replacing this domain with irrelevant sequences stabilized the protein but failed to restore Sry’s ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex-determining function in vivo. These functions were restored only when a VP16 transactivation domain was substituted. We conclude that the polyQ domain has important roles in protein stabilization and transcriptional activation, both of which are essential for male sex determination in mice. Our data disprove the hypothesis that the conserved HMG box domain is the only functional domain of Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel bifunctional module to activate Sox9 directly, whereas SRY proteins in other taxa, including humans, seem to lack this ability, presumably making them dependent on partner proteins(s) to provide this function. PMID:25074915

  14. Structure-function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination.

    Science.gov (United States)

    Zhao, Liang; Ng, Ee Ting; Davidson, Tara-Lynne; Longmuss, Enya; Urschitz, Johann; Elston, Marlee; Moisyadi, Stefan; Bowles, Josephine; Koopman, Peter

    2014-08-12

    The mammalian sex-determining factor SRY comprises a conserved high-mobility group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is essential for male sex determination. To dissect the molecular functions of this domain, we generated a series of Sry mutants, and studied their biochemical properties in cell lines and transgenic mouse embryos. Sry protein lacking the polyQ domain was unstable, due to proteasomal degradation. Replacing this domain with irrelevant sequences stabilized the protein but failed to restore Sry's ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex-determining function in vivo. These functions were restored only when a VP16 transactivation domain was substituted. We conclude that the polyQ domain has important roles in protein stabilization and transcriptional activation, both of which are essential for male sex determination in mice. Our data disprove the hypothesis that the conserved HMG box domain is the only functional domain of Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel bifunctional module to activate Sox9 directly, whereas SRY proteins in other taxa, including humans, seem to lack this ability, presumably making them dependent on partner proteins(s) to provide this function.

  15. AKT2 is essential to maintain podocyte viability and function during chronic kidney disease.

    Science.gov (United States)

    Canaud, Guillaume; Bienaimé, Frank; Viau, Amandine; Treins, Caroline; Baron, William; Nguyen, Clément; Burtin, Martine; Berissi, Sophie; Giannakakis, Konstantinos; Muda, Andrea Onetti; Zschiedrich, Stefan; Huber, Tobias B; Friedlander, Gérard; Legendre, Christophe; Pontoglio, Marco; Pende, Mario; Terzi, Fabiola

    2013-10-01

    In chronic kidney disease (CKD), loss of functional nephrons results in metabolic and mechanical stress in the remaining ones, resulting in further nephron loss. Here we show that Akt2 activation has an essential role in podocyte protection after nephron reduction. Glomerulosclerosis and albuminuria were substantially worsened in Akt2(-/-) but not in Akt1(-/-) mice as compared to wild-type mice. Specific deletion of Akt2 or its regulator Rictor in podocytes revealed that Akt2 has an intrinsic function in podocytes. Mechanistically, Akt2 triggers a compensatory program that involves mouse double minute 2 homolog (Mdm2), glycogen synthase kinase 3 (Gsk3) and Rac1. The defective activation of this pathway after nephron reduction leads to apoptosis and foot process effacement of the podocytes. We further show that AKT2 activation by mammalian target of rapamycin complex 2 (mTORC2) is also required for podocyte survival in human CKD. More notably, we elucidate the events underlying the adverse renal effect of sirolimus and provide a criterion for the rational use of this drug. Thus, our results disclose a new function of Akt2 and identify a potential therapeutic target for preserving glomerular function in CKD.

  16. Longitudinal strain predicts left ventricular mass regression after aortic valve replacement for severe aortic stenosis and preserved left ventricular function.

    Science.gov (United States)

    Gelsomino, Sandro; Lucà, Fabiana; Parise, Orlando; Lorusso, Roberto; Rao, Carmelo Massimiliano; Vizzardi, Enrico; Gensini, Gian Franco; Maessen, Jos G

    2013-11-01

    We explored the influence of global longitudinal strain (GLS) measured with two-dimensional speckle-tracking echocardiography on left ventricular mass regression (LVMR) in patients with pure aortic stenosis (AS) and normal left ventricular function undergoing aortic valve replacement (AVR). The study population included 83 patients with severe AS (aortic valve area regression (all P regression in patients with pure AS undergoing AVR. Our findings must be confirmed by further larger studies.

  17. Immediate and Longitudinal Alterations of Functional Networks after Thalamotomy in Essential Tremor

    Directory of Open Access Journals (Sweden)

    Changwon Jang

    2016-10-01

    Full Text Available Thalamotomy at the ventralis intermedius nucleus has been an effective treatment method for essential tremor, but how the brain network changes immediately responding to this deliberate lesion and then reorganizes afterwards are not clear. Taking advantage of a non-cranium-opening MRI-guided focused ultrasound ablation technique, we investigated functional network changes due to a focal lesion. To classify the diverse time courses of those network changes with respect to symptom-related long-lasting treatment effects and symptom-unrelated transient effects, we applied graph-theoretic analyses to longitudinal resting-state fMRI data before and 1 day, 7 days and 3 months after thalamotomy with essential tremor. We found reduced average connections among the motor-related areas, reduced connectivity between substantia nigra and external globus pallidum and reduced total connection in the thalamus after thalamotomy, which are all associated with clinical rating scales. The average connectivity among whole brain regions and inter-hemispheric network asymmetry show symptom-unrelated transient increases, indicating temporary reconfiguration of the whole brain network. In summary, thalamotomy regulates interactions over the motor network via symptom-related connectivity changes but accompanies transient, symptom-unrelated diaschisis in the global brain network. This study suggests the significance of longitudinal network analysis, combined with minimal-invasive treatment techniques, in understanding time-dependent diaschisis in the brain network due to a focal lesion.

  18. Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA

    Energy Technology Data Exchange (ETDEWEB)

    Hubin, Elizabeth A.; Fay, Allison; Xu, Catherine; Bean, James M.; Saecker, Ruth M.; Glickman, Michael S.; Darst, Seth A.; Campbell, Elizabeth A. (Rockefeller); (SKI)

    2017-01-09

    RbpA and CarD are essential transcription regulators in mycobacteria. Mechanistic analyses of promoter open complex (RPo) formation establish that RbpA and CarD cooperatively stimulate formation of an intermediate (RP2) leading to RPo; formation of RP2 is likely a bottleneck step at the majority of mycobacterial promoters. Once RPo forms, CarD also disfavors its isomerization back to RP2. We determined a 2.76 Å-resolution crystal structure of a mycobacterial transcription initiation complex (TIC) with RbpA as well as a CarD/RbpA/TIC model. Both CarD and RbpA bind near the upstream edge of the -10 element where they likely facilitate DNA bending and impede transcription bubble collapse. In vivo studies demonstrate the essential role of RbpA, show the effects of RbpA truncations on transcription and cell physiology, and indicate additional functions for RbpA not evident in vitro. This work provides a framework to understand the control of mycobacterial transcription by RbpA and CarD.

  19. Left Ventricular Diastolic Function in Essential Hypertensive Patients: Influence of Age and Left Ventricular Geometry

    Directory of Open Access Journals (Sweden)

    Rosa Eduardo Cantoni

    2002-01-01

    Full Text Available PURPOSE - To evaluate diastolic dysfunction (DD in essential hypertension and the influence of age and cardiac geometry on this parameter. METHODS - Four hundred sixty essential hypertensive patients (HT underwent Doppler echocardiography to obtain E/A wave ratio (E/A, atrial deceleration time (ADT, and isovolumetric relaxation time (IRT. All patients were grouped according to cardiac geometric patterns (NG - normal geometry; CR - concentric remodeling; CH- concentric hypertrophy; EH - eccentric hypertrophy and to age (60 years. One hundred six normotensives (NT persons were also evaluated. RESULTS - A worsening of diastolic function in the HT compared with the NT, including HT with NG (E/A: NT - 1.38±0.03 vs HT - 1.27±0.02, p<0.01, was observed. A higher prevalence of DD occurred parallel to age and cardiac geometry also in the prehypertrophic groups (CR. Multiple regression analysis identified age as the most important predictor of DD (r²=0.30, p<0.01. CONCLUSION - DD was prevalent in this hypertensive population, being highly affected by age and less by heart structural parameters. DD is observed in incipient stages of hypertensive heart disease, and thus its early detection may help in the risk stratification of hypertensive patients.

  20. Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA.

    Science.gov (United States)

    Hubin, Elizabeth A; Fay, Allison; Xu, Catherine; Bean, James M; Saecker, Ruth M; Glickman, Michael S; Darst, Seth A; Campbell, Elizabeth A

    2017-01-09

    RbpA and CarD are essential transcription regulators in mycobacteria. Mechanistic analyses of promoter open complex (RPo) formation establish that RbpA and CarD cooperatively stimulate formation of an intermediate (RP2) leading to RPo; formation of RP2 is likely a bottleneck step at the majority of mycobacterial promoters. Once RPo forms, CarD also disfavors its isomerization back to RP2. We determined a 2.76 Å-resolution crystal structure of a mycobacterial transcription initiation complex (TIC) with RbpA as well as a CarD/RbpA/TIC model. Both CarD and RbpA bind near the upstream edge of the -10 element where they likely facilitate DNA bending and impede transcription bubble collapse. In vivo studies demonstrate the essential role of RbpA, show the effects of RbpA truncations on transcription and cell physiology, and indicate additional functions for RbpA not evident in vitro. This work provides a framework to understand the control of mycobacterial transcription by RbpA and CarD.

  1. Beadex Function in the Motor Neurons Is Essential for Female Reproduction in Drosophila melanogaster

    Science.gov (United States)

    Kairamkonda, Subhash; Nongthomba, Upendra

    2014-01-01

    Drosophila melanogaster has served as an excellent model system for understanding the neuronal circuits and molecular mechanisms regulating complex behaviors. The Drosophila female reproductive circuits, in particular, are well studied and can be used as a tool to understand the role of novel genes in neuronal function in general and female reproduction in particular. In the present study, the role of Beadex, a transcription co-activator, in Drosophila female reproduction was assessed by generation of mutant and knock down studies. Null allele of Beadex was generated by transposase induced excision of P-element present within an intron of Beadex gene. The mutant showed highly compromised reproductive abilities as evaluated by reduced fecundity and fertility, abnormal oviposition and more importantly, the failure of sperm release from storage organs. However, no defect was found in the overall ovariole development. Tissue specific, targeted knock down of Beadex indicated that its function in neurons is important for efficient female reproduction, since its neuronal knock down led to compromised female reproductive abilities, similar to Beadex null females. Further, different neuronal class specific knock down studies revealed that Beadex function is required in motor neurons for normal fecundity and fertility of females. Thus, the present study attributes a novel and essential role for Beadex in female reproduction through neurons. PMID:25396431

  2. Timed Knickkopf function is essential for wing cuticle formation in Drosophila melanogaster.

    Science.gov (United States)

    Li, Kaixia; Zhang, Xubo; Zuo, Ying; Liu, Weimin; Zhang, Jianzhen; Moussian, Bernard

    2017-10-01

    The insect cuticle is an extracellular matrix that consists of the polysaccharide chitin, proteins, lipids and organic molecules that are arranged in distinct horizontal layers. In Drosophila melanogaster, these layers are not formed sequentially, but, at least partially, at the same time. Timing of the underlying molecular mechanisms is conceivably crucial for cuticle formation. To study this issue, we determined the time period during which the function of Knickkopf (Knk), a key factor of chitin organization, is required for wing cuticle differentiation in D. melanogaster. Although knk is expressed throughout metamorphosis, we demonstrate that its expression 30 h prior and 48 h after pupariation is essential for correct wing cuticle formation. In other words, expression beyond this period is futile. Importantly, manipulation of Knk expression during this time causes wing bending suggesting an effect of Knk amounts on the physical properties of the wing cuticle. Manipulation of Knk expression also interferes with the structure and function of the cuticle surface. First, we show that the shape of surface nano-structures depends on the expression levels of knk. Second, we find that cuticle impermeability is compromised in wings with reduced knk expression. In summary, despite the extended supply of Knk during metamorphosis, controlled amounts of Knk are important for correct wing cuticle differentiation and function in a concise period of time. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Early self-managed focal sensorimotor rehabilitative training enhances functional mobility and sensorimotor function in patients following total knee replacement: a controlled clinical trial.

    Science.gov (United States)

    Moutzouri, Maria; Gleeson, Nigel; Coutts, Fiona; Tsepis, Elias; John, Gliatis

    2018-02-01

    To assess the effects of early self-managed focal sensorimotor training compared to functional exercise training after total knee replacement on functional mobility and sensorimotor function. A single-blind controlled clinical trial. University Hospital of Rion, Greece. A total of 52 participants following total knee replacement. The primary outcome was the Timed Up and Go Test and the secondary outcomes were balance, joint position error, the Knee Outcome Survey Activities of Daily Living Scale, and pain. Patients were assessed on three separate occasions (presurgery, 8 weeks post surgery, and 14 weeks post surgery). Participants were randomized to either focal sensorimotor exercise training (experimental group) or functional exercise training (control group). Both groups received a 12-week home-based programme prescribed for 3-5 sessions/week (35-45 minutes). Consistently greater improvements ( F 2,98  = 4.3 to 24.8; P functional mobility and sensorimotor function endorses using focal sensorimotor training as an effective mode of rehabilitation following knee replacement.

  4. Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression.

    Directory of Open Access Journals (Sweden)

    Sathidpak Nantasanti

    Full Text Available The tumor suppressors Retinoblastoma (Rb and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver for metabolizing therapeutic drugs or toxins. We demonstrate that Rb and p53 cooperate to metabolize the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC. DDC is metabolized mainly by cytochrome P450 (Cyp3a enzymes resulting in inhibition of heme synthesis and accumulation of protoporphyrin, an intermediate of heme pathway. Protoporphyrin accumulation causes bile injury and ductular reaction. We show that loss of Rb and p53 resulted in reduced Cyp3a expression decreased accumulation of protoporphyrin and consequently less ductular reaction in livers of mice fed with DDC for 3 weeks. These findings provide strong evidence that synergistic functions of Rb and p53 are essential for metabolism of DDC. Because Rb and p53 functions are frequently disabled in liver diseases, our results suggest that liver patients might have altered ability to remove toxins or properly metabolize therapeutic drugs. Strikingly the reduced biliary injury towards the oxidative stress inducer DCC was accompanied by enhanced hepatocellular injury and formation of HCCs in Rb and p53 deficient livers. The increase in hepatocellular injury might be related to reduce protoporphyrin accumulation, because protoporphrin is well known for its anti-oxidative activity. Furthermore our results indicate that Rb and p53 not only function as tumor suppressors in response to carcinogenic injury, but also in response to non-carcinogenic injury such as DDC.

  5. The asparaginyl endopeptidase legumain is essential for functional recovery after spinal cord injury in adult zebrafish.

    Directory of Open Access Journals (Sweden)

    Liping Ma

    Full Text Available Unlike mammals, adult zebrafish are capable of regenerating severed axons and regaining locomotor function after spinal cord injury. A key factor for this regenerative capacity is the innate ability of neurons to re-express growth-associated genes and regrow their axons after injury in a permissive environment. By microarray analysis, we have previously shown that the expression of legumain (also known as asparaginyl endopeptidase is upregulated after complete transection of the spinal cord. In situ hybridization showed upregulation of legumain expression in neurons of regenerative nuclei during the phase of axon regrowth/sprouting after spinal cord injury. Upregulation of Legumain protein expression was confirmed by immunohistochemistry. Interestingly, upregulation of legumain expression was also observed in macrophages/microglia and neurons in the spinal cord caudal to the lesion site after injury. The role of legumain in locomotor function after spinal cord injury was tested by reducing Legumain expression by application of anti-sense morpholino oligonucleotides. Using two independent anti-sense morpholinos, locomotor recovery and axonal regrowth were impaired when compared with a standard control morpholino. We conclude that upregulation of legumain expression after spinal cord injury in the adult zebrafish is an essential component of the capacity of injured neurons to regrow their axons. Another feature contributing to functional recovery implicates upregulation of legumain expression in the spinal cord caudal to the injury site. In conclusion, we established for the first time a function for an unusual protease, the asparaginyl endopeptidase, in the nervous system. This study is also the first to demonstrate the importance of legumain for repair of an injured adult central nervous system of a spontaneously regenerating vertebrate and is expected to yield insights into its potential in nervous system regeneration in mammals.

  6. Function analysis of a new type I PKS-SAT domain by SAT-EAT domain replacement.

    Science.gov (United States)

    Jiao, Y L; Wang, L H; Jiao, B H; Wang, S J; Fang, Y W; Liu, S

    2010-01-01

    The function of a new starter unit acyltransferase (SAT) domain SAT-EF080951 (GenBank accession number) encoded in a new type I polyketide synthase (PKS) gene cluster EF568935 (GenBank accession number) isolated for this study was analyzed by domain replacement with an extender unit AT (EAT) domain of avermectin PKS. It was shown that the SAT-EF080951 incorporated malonyl-CoA specifically in vivo, which contradicted the specificity that we had previously determined by substrate binding test in vitro. The result of this study indicates that type I PKS-SAT can alter its specificity in vivo and functions well in extender units and proved the feasibility of the SAT-EAT domain replacement in type I PKS. We propose that SAT-EAT replacement strategy could be a novel route for increasing the diversity of new polyketides combinatorially biosynthesized. The new type I PKS-SAT-EF080951 studied herein may be further employed for related studies on enzymology or combinatorial biosynthesis of polyketides.

  7. Functional MRI for immediate monitoring stereotactic thalamotomy in a patient with essential tremor

    Energy Technology Data Exchange (ETDEWEB)

    Hesselmann, Volker; Schaaf, Maike; Krug, Barbara; Lackner, Klaus [University of Cologne, Department of Radiology, Cologne (Germany); Maarouf, Mohammed; Hunsche, Stefan; Sturm, Volker [University of Cologne, Department of Stereotaxy and Functional Neurosurgery, Cologne (Germany); Lasek, Kathrin [Universitaetsklinikum Schleswig Holstein, Klinik fuer Neurologie, Luebeck (Germany); Wedekind, Christoph [Akademisches Lehrkrankenhaus der Universitaet Erlangen-Nuernberg, Belegabteilung fuer Neurochirurgie, Klinikum Bamberg, Bamberg (Germany)

    2006-10-15

    The effect of stereotactic thalamotomy was assessed with pre- and postoperative functional magnetic resonance imaging (fMRI) under motor stimulation. A patient with unilateral essential tremor (ET) of the left arm underwent stereotactically guided thalamotomy of the right ventral intermediate thalamic nucleus (VIM). FMRI was done directly before and after surgery on a 1.5-Tesla scanner. The stimulation paradigm was maintainance of the affected arm in an extended position and hand clenching being performed in a block design manner. Statistical analysis was done with Brain Voyager 2000. After thalamotomy the tremor diminished completely. As a difference between the pre- and postoperative fMRI, a significant activation was found in the VIM contralateral to the activation site, adjacent to the inferior olivary nucleus contralateral to the activation site and in the dorsal cingulum. In conclusion, fMRI can detect the functional effect of thalamotomy for tremor treatment. Direct postoperative fMRI provides a sufficient method for estimating the effect of thalamotomy immediately after intervention. The importance of the intermediate thalamic nucleus and the olivary nucleus in tremor generation is supported by our findings. (orig.)

  8. Characteristics of functional state of arteriolar and venular skin microvessels in patients with essential arterial hypertension.

    Science.gov (United States)

    Fedorovich, Andrey A; Rogoza, Anatoly N; Chikhladze, Novella M

    2014-05-01

    The aim of the study was to evaluate the vasomotor activity of skin precapillary arterioles, depending on the condition of blood outflow from the capillary bed in patients with essential arterial hypertension (AH). The study included 30 normotensive subjects (NT) and 63 patients with AH, who were tested with a laser Doppler flowmetry with wavelet analysis of blood flow oscillations on the right forearm and ambulatory blood pressure monitoring (ABPM) on the left shoulder. Antihypertensive therapy was stopped for all patients 14 days prior to the experiment or AH was diagnosed for the first time. The hypertensive patients were divided into 2 groups, depending on the amplitude of the respiratory blood flow oscillations in skin microvessels. The first group included 30 patients without blood outflow violations of the capillary bed (AHVN), the second group consisted of 33 patients with various intensity of functional disorders in venular sector of microvasculature (AHVS). If the value of the amplitude of blood flow oscillations can be related to the tone" definition, then AHVN patients have a significant increase in neurogenic component of vascular tone (phypertensive patients can have significant differences in the functional state of microvessels. The assessment of the initial skin microvasculatory regulatory mechanism status could potentially be useful for individual choice of antihypertensive therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. A Function Essential to Viral Entry Underlies the Hepatitis B Virus “a” Determinant▿

    Science.gov (United States)

    Salisse, Jessica; Sureau, Camille

    2009-01-01

    The hepatitis B virus (HBV) particles bear a receptor-binding site located in the pre-S1 domain of the large HBV envelope protein. Using the hepatitis delta virus (HDV) as a surrogate of HBV, a second infectivity determinant was recently identified in the envelope proteins antigenic loop (AGL), and its activity was shown to depend upon cysteine residues that are essential for the structure of the HBV immunodominant “a” determinant. Here, an alanine-scanning mutagenesis approach was used to precisely map the AGL infectivity determinant to a set of conserved residues, which are predicted to cluster together with cysteines in the AGL disulfide bridges network. Several substitutions suppressed both infectivity and the “a” determinant, whereas others were infectivity deficient with only a partial impact on antigenicity. Interestingly, G145R, a substitution often arising under immune pressure selection and detrimental to the “a” determinant, had no effect on infectivity. Altogether, these findings indicate that the AGL infectivity determinant is closely related to, yet separable from, the “a” determinant. Finally, a selection of HDV entry-deficient mutations were introduced at the surface of HBV virions and shown to also abrogate infection in the HBV model. Therefore, a function can at last be assigned to the orphan “a” determinant, the first-discovered marker of HBV infection. The characterization of the AGL functions at viral entry may lead to novel approaches in the development of antivirals against HBV. PMID:19570861

  10. A function essential to viral entry underlies the hepatitis B virus "a" determinant.

    Science.gov (United States)

    Salisse, Jessica; Sureau, Camille

    2009-09-01

    The hepatitis B virus (HBV) particles bear a receptor-binding site located in the pre-S1 domain of the large HBV envelope protein. Using the hepatitis delta virus (HDV) as a surrogate of HBV, a second infectivity determinant was recently identified in the envelope proteins antigenic loop (AGL), and its activity was shown to depend upon cysteine residues that are essential for the structure of the HBV immunodominant "a" determinant. Here, an alanine-scanning mutagenesis approach was used to precisely map the AGL infectivity determinant to a set of conserved residues, which are predicted to cluster together with cysteines in the AGL disulfide bridges network. Several substitutions suppressed both infectivity and the "a" determinant, whereas others were infectivity deficient with only a partial impact on antigenicity. Interestingly, G145R, a substitution often arising under immune pressure selection and detrimental to the "a" determinant, had no effect on infectivity. Altogether, these findings indicate that the AGL infectivity determinant is closely related to, yet separable from, the "a" determinant. Finally, a selection of HDV entry-deficient mutations were introduced at the surface of HBV virions and shown to also abrogate infection in the HBV model. Therefore, a function can at last be assigned to the orphan "a" determinant, the first-discovered marker of HBV infection. The characterization of the AGL functions at viral entry may lead to novel approaches in the development of antivirals against HBV.

  11. The use of clinical analysis of movements in evaluation of motor functional status of patients after total hip replacement

    Directory of Open Access Journals (Sweden)

    Romakina N.A.

    2016-06-01

    Full Text Available Aim: to estimate functional status of coxarthrosis in patients requiring total hip replacement of the two hip joints. Material and methods. The biomechanical examination of 94 patients with bilateral primary coxarthrosis before and after total hip replacement was performed using clinical stabilometric software complex. The ability to perceive the mechanical load during standing and walking was evaluated at different stages of the treatment. The difference between the samples was estimated with the use of Mann — Whitney U-test. The rank correlation of biomechanical parameters was measured by Spearman coefficient. Results. It was revealed that the most responsive indicators are the transfer period, the first and second periods of double support and the deviation of the center of pressure relative to the average position in the frontal plane. Conclusion. After surgical treatment there was observed some improvement: the-left-and-right-step asymmetry decrease, rhythm rate increase, improved ability to maintain body balance, jog reactions increase.

  12. Halloysite nanotubes loaded with peppermint essential oil as filler for functional biopolymer film.

    Science.gov (United States)

    Biddeci, G; Cavallaro, G; Di Blasi, F; Lazzara, G; Massaro, M; Milioto, S; Parisi, F; Riela, S; Spinelli, G

    2016-11-05

    The purpose of this paper is to show how a functional bionanocomposite film with both antioxidant and antimicrobial activities was successfully prepared by the filling of a pectin matrix with modified Halloysite nanotubes (HNT) containing the essential peppermint oil (PO). Firstly, HNT surfaces were functionalized with cucurbit[6]uril (CB[6]) molecules with the aim to enhance the affinity of the nanofiller towards PO, which was estimated by means of HPLC experiments. The HNT/CB[6] hybrid was characterized by several methods (thermogravimetry, FT-IR spectroscopy and scanning electron microscopy) highlighting the influence of the supramolecular interactions on the composition, thermal behavior and morphology of the filler. Then, a pectin+HNT/CB[6] biofilm was prepared by the use of the casting method under specific experimental conditions in order to favor the entrapment of the volatile PO into the nanocomposite structure. Water contact angle measurements, thermogravimetry and tensile tests evidenced the effects of the modified filler on the thermo-mechanical and wettability properties of pectin, which were correlated to the microscopic structure of the biocomposite film. In addition, PO release in food simulant solvent was investigated at different temperatures (4 and 25°C), whereas the antioxidant activity of the nanocomposite film was estimated using the DPPH method. Finally, we studied the in vitro antibacterial activity of the biofilm against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive), which were isolated by beef and cow milk, respectively. These experiments were carried out at specific temperatures (4, 37 and 65°C) that can be useful for a multi-step food conservation. This paper puts forwards an easy strategy to prepare a functional sustainable edible film with thermo-sensitive antioxidant/antimicrobial activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Fe(III Is Essential for Porcine Embryonic Development via Mitochondrial Function Maintenance.

    Directory of Open Access Journals (Sweden)

    Ming-Hui Zhao

    Full Text Available Iron is an important trace element involved in several biological processes. The role of iron in porcine early embryonic development remains unknown. In the present study, we depleted iron (III, Fe3+ with deferoxamine (DFM, a specific Fe3+ chelator, in cultured porcine parthenotes and monitored embryonic development, apoptosis, mitochondrial membrane potential, and ATP production. Results showed biphasic function of Fe3+ in porcine embryo development. 0.5 μM DFM obviously increased blastocyst formation (57.49 ± 2.18% vs. control, 43.99 ± 1.72%, P < 0.05 via reduced (P < 0.05 production of reactive oxygen species (ROS, further increased mitochondrial membrane potential and ATP production in blastocysts (P < 0.05. 0.5 μM DFM decreased mRNA expression of Caspase 3 (Casp3 and increased Bcl-xL. However, results showed a significant reduction in blastocyst formation in the presence of 5.0 μM DFM compared with the control group (DFM, 21.62 ± 3.92% vs. control, 43.99 ± 1.73%, P < 0.05. Fe3+ depletion reduced the total (DFM, 21.10 ± 8.78 vs. control, 44.09 ± 13.65, P < 0.05 and increased apoptotic cell number (DFM, 11.10 ± 5.24 vs. control, 2.64 ± 1.43, P < 0.05 in the blastocyst. An obvious reduction in mitochondrial membrane potential and ATP level after 5.0 μM DFM treatment was observed. Co-localization between mitochondria and cytochrome c was reduced after high concentration of DFM treatment. In conclusion, Fe3+ is essential for porcine embryonic development via mitochondrial function maintenance, but redundant Fe3+ impairs the function of mitochondria.

  14. LINE retrotransposon RNA is an essential structural and functional epigenetic component of a core neocentromeric chromatin.

    Directory of Open Access Journals (Sweden)

    Anderly C Chueh

    2009-01-01

    Full Text Available We have previously identified and characterized the phenomenon of ectopic human centromeres, known as neocentromeres. Human neocentromeres form epigenetically at euchromatic chromosomal sites and are structurally and functionally similar to normal human centromeres. Recent studies have indicated that neocentromere formation provides a major mechanism for centromere repositioning, karyotype evolution, and speciation. Using a marker chromosome mardel(10 containing a neocentromere formed at the normal chromosomal 10q25 region, we have previously mapped a 330-kb CENP-A-binding domain and described an increased prevalence of L1 retrotransposons in the underlying DNA sequences of the CENP-A-binding clusters. Here, we investigated the potential role of the L1 retrotransposons in the regulation of neocentromere activity. Determination of the transcriptional activity of a panel of full-length L1s (FL-L1s across a 6-Mb region spanning the 10q25 neocentromere chromatin identified one of the FL-L1 retrotransposons, designated FL-L1b and residing centrally within the CENP-A-binding clusters, to be transcriptionally active. We demonstrated the direct incorporation of the FL-L1b RNA transcripts into the CENP-A-associated chromatin. RNAi-mediated knockdown of the FL-L1b RNA transcripts led to a reduction in CENP-A binding and an impaired mitotic function of the 10q25 neocentromere. These results indicate that LINE retrotransposon RNA is a previously undescribed essential structural and functional component of the neocentromeric chromatin and that retrotransposable elements may serve as a critical epigenetic determinant in the chromatin remodelling events leading to neocentromere formation.

  15. Xenotransplantation of Embryonic Pig Kidney or Pancreas to Replace the Function of Mature Organs

    Directory of Open Access Journals (Sweden)

    Marc R. Hammerman

    2011-01-01

    Full Text Available Lack of donor availability limits the number of human donor organs. The need for host immunosuppression complicates transplantation procedures. Ultrastructurally precise kidneys differentiate in situ following xenotransplantation in mesentery of embryonic pig renal primordia. The developing organ attracts its blood supply from the host, obviating humoral rejection. Engraftment of pig renal primordia transplanted directly into rats requires host immune suppression. However, insulin-producing cells originating from embryonic pig pancreas obtained very early following initiation of organogenesis [embryonic day 28 (E28] engraft long term in nonimmune-suppressed diabetic rats or rhesus macaques. Engraftment of morphologically similar cells originating from adult porcine islets of Langerhans (islets occurs in rats previously transplanted with E28 pig pancreatic primordia. Here, we review recent findings germane to xenotransplantation of pig renal or pancreatic primordia as a novel organ replacement strategy.

  16. Functional regions in the essential light chain of smooth muscle myosin as revealed by the mutagenesis approach.

    Science.gov (United States)

    Quevillon-Chéruel, S; Janmot, C; Nozais, M; Lompré, A M; Béchet, J J

    2000-10-01

    The endogenous essential light chain (LC17) of myosin from intestine smooth muscle was replaced with mutated essential light chains prepared using recombinant techniques. Complete exchange was observed with histidine-tagged derivatives of LC17a, LC17b and E122A-LC17a (LC17a and LC17b are the usual constituants of smooth muscle myosin), with small changes in the ATPase activity of reconstituted myosins. Much less exchange was observed with the light-chain derivative lacking the last 12 amino acid residues, demonstrating the importance of this segment, which may act as one arm of a pair of pincers to bind the myosin heavy chain.

  17. Daily evaluation of organ function during renal replacement therapy in intensive care unit patients with acute renal failure.

    Science.gov (United States)

    Cappi, Sylas B; Sakr, Yasser; Vincent, Jean-Louis

    2006-06-01

    The aim of this study was to assess changes in organ function in acute renal failure patients during renal replacement therapy and relate them to outcome. Medical and nursing charts from 111 patients with acute renal failure who underwent renal replacement therapy (hemodialysis or hemofiltration) from July 2000 until July 2002 on a 31-bed medicosurgical intensive care unit (ICU) at a university hospital in Belgium and in whom the Sequential Organ Failure Assessment (SOFA) score was calculated daily before the start of therapy until the seventh day, or the end of therapy, were analyzed. Changes in SOFA score over time (Delta SOFA) were calculated. Of 111 patients, 63 (57%) died in the ICU. Nonsurvivors were older (68 [52-76] vs 59 [48-70] years, P = .017) and had initially higher respiratory, cardiovascular, and total SOFA scores compared with survivors. A greater Delta renal SOFA at 24 hours was associated univariantly with a higher risk of ICU mortality (odds ratio, 1.7; 95% confidence interval, 1.2-2.6; P = .013). In a multivariate analysis with ICU outcome as the dependent variable, only age, cardiovascular SOFA score on admission, and the change in total SOFA score over the first 24 hours were independently associated with a greater risk of death. Assessment of these factors in the first 24 hours of renal replacement therapy could help identify patients at higher risk of mortality early during their ICU admission.

  18. Maintenance of vascular integrity by pericytes is essential for normal kidney function

    Science.gov (United States)

    Lemos, Dario R.; Marsh, Graham; Huang, Angela; Campanholle, Gabriela; Aburatani, Takahide; Dang, Lan; Gomez, Ivan; Fisher, Ken; Ligresti, Giovanni; Peti-Peterdi, Janos

    2016-01-01

    Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested the hypothesis that kidney pericytes, derived from FoxD1+ mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, blood urea nitrogen, and albuminuria within 96 h indicated acute kidney injury in pericyte-ablated mice. Loss of pericytes led to a rapid accumulation of neutral lipid vacuoles, swollen mitochondria, and apoptosis in tubular epithelial cells. Pericyte ablation led to endothelial cell swelling, reduced expression of vascular homeostasis markers, and peritubular capillary loss. Despite the observed injury, no signs of the acute inflammatory response were observed. Pathway enrichment analysis of genes expressed in kidney pericytes in vivo identified basement membrane proteins, angiogenic factors, and factors regulating vascular tone as major regulators of vascular function. Using novel microphysiological devices, we recapitulated human kidney peritubular capillaries coated with pericytes and showed that pericytes regulate permeability, basement membrane deposition, and microvascular tone. These findings suggest that through the active support of the microvasculature, pericytes are essential to adult kidney homeostasis. PMID:27335372

  19. Pam heterozygous mice reveal essential role for Cu in amygdalar behavioral and synaptic function.

    Science.gov (United States)

    Gaier, Eric D; Eipper, Betty A; Mains, Richard E

    2014-05-01

    Copper (Cu) is an essential element with many biological roles, but its roles in the mammalian nervous system are poorly understood. Mice deficient in the cuproenzyme peptidylglycine α-amidating monooxygenase (Pam(+/-) mice) were initially generated to study neuropeptide amidation. Pam(+/-) mice exhibit profound deficits in a few behavioral tasks, including enhancements in innate fear along with deficits in acquired fear. Interestingly, several Pam(+/-) phenotypes were recapitulated in Cu-restricted wild-type mice and rescued in Cu-supplemented Pam(+/-) mice. These behaviors correspond to enhanced excitability and deficient synaptic plasticity in the amygdala of Pam(+/-) mice, which are also rescued by Cu supplementation. Cu and ATP7A are present at synapses, in key positions to respond to and influence synaptic activity. Further study demonstrated that extracellular Cu is necessary for wild-type synaptic plasticity and sufficient to induce long-term potentiation. These experiments support roles for PAM in Cu homeostasis and for synaptic Cu in amygdalar function. © 2014 New York Academy of Sciences.

  20. Association between asymmetric dimethylarginine and indices of vascular function in patients with essential hypertension.

    Science.gov (United States)

    Serg, Martin; Kampus, Priit; Kals, Jaak; Zagura, Maksim; Muda, Piibe; Tuomainen, Tomi-Pekka; Zilmer, Kersti; Salum, Erik; Zilmer, Mihkel; Eha, Jaan

    2011-04-01

    Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is associated with endothelial dysfunction. The aim of the present study was to investigate the relationship between ADMA, indices of arterial stiffness, endothelial function and carotid artery intima-media thickness (IMT) in hypertension patients. Eighty middle-aged (47 ± 10 years) untreated patients with mild to moderate essential hypertension underwent routine physical examination, pulse wave analysis (PWA), measurement of aortic pulse wave velocity (PWV) and IMT. In PWA, administration of salbutamol and nitroglycerine was used to assess endothelium-dependent (EDV) and endothelium-independent vasodilation, respectively. In univariate analysis, ADMA was correlated with EDV (r = -0.26; p = 0.02) and IMT (r = 0.32; p = 0.007). In multiple regression analysis, ADMA was independently associated with the female gender, EDV, IMT and total cholesterol (R(2) = 0.30; p < 0.001). No correlation was detected between ADMA and augmentation index, central/brachial blood pressure or aortic PWV. In hypertension patients, ADMA is independently correlated with IMT and EDV. Thus, ADMA is a marker of endothelial dysfunction and intima-media thickening in patients with hypertension.

  1. Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction

    Energy Technology Data Exchange (ETDEWEB)

    Muthu, Priya; Wang, Li; Yuan, Chen-Ching; Kazmierczak, Katarzyna; Huang, Wenrui; Hernandez, Olga M.; Kawai, Masataka; Irving, Thomas C.; Szczesna-Cordary, Danuta (IIT); (Iowa); (Miami-MED)

    2012-04-02

    The myosin essential light chain (ELC) is a structural component of the actomyosin cross-bridge, but its function is poorly understood, especially the role of the cardiac specific N-terminal extension in modulating actomyosin interaction. Here, we generated transgenic (Tg) mice expressing the A57G (alanine to glycine) mutation in the cardiac ELC known to cause familial hypertrophic cardiomyopathy (FHC). The function of the ELC N-terminal extension was investigated with the Tg-{Delta}43 mouse model, whose myocardium expresses a truncated ELC. Low-angle X-ray diffraction studies on papillary muscle fibers in rigor revealed a decreased interfilament spacing ({approx} 1.5 nm) and no alterations in cross-bridge mass distribution in Tg-A57G mice compared to Tg-WT, expressing the full-length nonmutated ELC. The truncation mutation showed a 1.3-fold increase in I{sub 1,1}/I{sub 1,0}, indicating a shift of cross-bridge mass from the thick filament backbone toward the thin filaments. Mechanical studies demonstrated increased stiffness in Tg-A57G muscle fibers compared to Tg-WT or Tg-{Delta}43. The equilibrium constant for the cross-bridge force generation step was smallest in Tg-{Delta}43. These results support an important role for the N-terminal ELC extension in prepositioning the cross-bridge for optimal force production. Subtle changes in the ELC sequence were sufficient to alter cross-bridge properties and lead to pathological phenotypes.

  2. Incidence of total hip or knee replacement due to osteoarthritis in relation to thyroid function: a prospective cohort study (The Nord-Trøndelag Health Study)

    OpenAIRE

    Hellevik, Alf Inge; Johnsen, Marianne Bakke; Langhammer, Arnulf; Fenstad, Anne Marie; Furnes, Ove; Storheim, Kjersti; Zwart, John-Anker; Flugsrud, Gunnar B; Nordsletten, Lars

    2017-01-01

    Background To study whether thyroid function was associated with risk of hip or knee replacement due to primary osteoarthritis. Methods In a prospective cohort study, data from the second and third survey of the Nord-Trøndelag Health Study were linked to the Norwegian Arthroplasty Register in order to identify total hip or knee replacement as a result of primary osteoarthritis. ...

  3. Long-term consequences of growth hormone replacement and cranial radiation on pituitary function

    NARCIS (Netherlands)

    Appelman-Dijkstra, Natasha Mireille

    2015-01-01

    This thesis covers the consequences of cranial irradiation of non-pituitary tumors, eg nasopharyngeal carcinoma, on pituitary function. In chapter 2 we have performed a meta-analysis of available data reported in literature on pituitary function after cranial radiotherapy for head and neck and

  4. Effect of preoperative neuromuscular training (NEMEX-TJR) on functional outcome after total knee replacement

    DEFF Research Database (Denmark)

    Huber, Erika O; Roos, Ewa M.; Meichtry, André

    2015-01-01

    BACKGROUND: Improving functional status preoperatively through exercise may improve postoperative outcome. Previous knowledge on preoperative exercise in knee osteoarthritis is insufficient. The aim of the study was to compare the difference in change between groups in lower extremity function from...... sessions of KS or 3 sessions of KS alone. Function was assessed with the Chair Stand Test (CST, primary endpoint) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales focusing on daily living function (ADL) and pain (secondary endpoints). Assessments were performed immediately before...... pain the treatment effect was -4.9 points (-16.3, 6.5) and -3.3 points (-13.5, 6.8) respectively. CONCLUSIONS: A median (IQR) of 10 (8, 14) exercise sessions before surgery showed an additional small but non-significant improvement in all functional assessments compared to patient education alone...

  5. Abnormal vibration induced illusion of movement in essential tremor: evidence for abnormal muscle spindle afferent function

    OpenAIRE

    Frima, N; Grunewald, R

    2005-01-01

    Objectives: Vibration induced illusion of movement (VIIM) is abnormal in patients with idiopathic focal dystonia, an abnormality which corrects with fatigue of the vibrated muscle. Since dystonia and essential tremor sometimes coexist in families, we investigated the perception of VIIM and the effect of fatigue on VIIM in patients with essential tremor.

  6. INFLUENCES OF HORMONE REPLACEMENT THERAPY ON OLFACTORY AND COGNITIVE FUNCTION IN THE MENOPAUSE

    Science.gov (United States)

    Doty, Richard L.; Tourbier, Isabelle; Ng, Victoria; Neff, Jessica; Armstrong, Deborah; Battistini, Michelle; Sammel, Mary D.; Gettes, David; Evans, Dwight L.; Mirza, Natasha; Moberg, Paul J.; Connolly, Tim; Sondheimer, Steven J.

    2015-01-01

    Olfactory dysfunction can be an early sign of Alzheimer’s disease (AD). Since hormone replacement therapy (HRT) may protect against developing AD in postmenopausal women, the question arises as to whether it also protects against olfactory dysfunction in such women. Three olfactory and 12 neurocognitive tests were administered to 432 healthy postmenopausal women with varied HRT histories. Serum levels of reproductive hormones were obtained for all subjects; APOE-ε4 haplotype was determined for 77. National Adult Reading Test and Odor Memory/Discrimination Test (OMT) scores were positively influenced by HRT. Odor identification and OMT test scores were lower for women who scored poorly on a delayed recall test, a surrogate for mild cognitive impairment. WAIS-R NI Spatial Span Backwards Test scores were higher in women receiving estrogen plus progestin HRT and directly correlated with serum testosterone levels, the latter implying a positive effect of testosterone on spatial memory. APOE-ε4 was associated with poorer odor threshold test scores. These data suggest that HRT positively influences a limited number of olfactory and cognitive measures in the menopause. PMID:25850354

  7. Greening in sunflower butter cookies as a function of egg replacers and baking temperature.

    Science.gov (United States)

    Rogers, Amanda; Hahn, Lan; Pham, Vu; Were, Lilian

    2018-04-01

    Chlorogenic acid (CGA) binding to proteins in alkaline conditions results in the production of green trihydroxy benzacradine (TBA) derivatives. The formation of TBA derivatives could decrease product quality due to the potential losses in soluble protein and antioxidants and the production of an undesirable green color. To determine how cookie formulation affected the formation of TBA derivatives in sunflower butter cookies, two egg replacers (chia and banana) and two baking temperatures (162.8 and 190.6 °C) were used. Moisture, greening intensity, CGA content and antioxidant capacity were measured. Cookies made with egg and baked at 162.8 °C had the highest moisture, internal greening intensity, and TBA derivative formation, in addition to lower CGA content and antioxidant capacity. Cookies made with banana baked at 190.6 °C produced the opposite outcome with 35, 4, and 23% less internal greening, moisture, and TBA derivatives, respectively, and 90 and 76% higher CGA and antioxidant capacity. Internal greening was positively correlated with moisture and adduct concentration, and negatively correlated with spread factor and CGA content. Moisture had a significant impact on greening, which indicates that baking temperature and cookie dough formulation can be modified to produce a less green cookie with more unreacted antioxidants and protein.

  8. Estrogen replacement, muscle composition, and physical function: the Health ABC Study

    NARCIS (Netherlands)

    Taaffe, D.R.; Newman, A.B.; Haggerty, C.L.; Colbert, L.H.; de Rekeneire, N.; Visser, M.; Goodpaster, B.H.; Nevitt, M.C.; Tylavsky, F.A.; Harris, T.B.

    2005-01-01

    PURPOSE: Although the beneficial effects of estrogen use on cardiovascular and cognitive function in postmenopausal women have been recently discredited, controversy remains regarding its usefulness for maintaining skeletal muscle mass or strength. Therefore, the purpose of this study was to

  9. Estrogen replacement, muscle composition, and physical function : The Health ABC Study

    NARCIS (Netherlands)

    Taaffe, Dennis R; Newman, Anne B; Haggerty, Catherine L; Colbert, Lisa H; de Rekeneire, Nathalie; Visser, Marjolein; Goodpaster, Bret H; Nevitt, Michael C; Tylavsky, Frances A; Harris, Tamara B

    2005-01-01

    PURPOSE: Although the beneficial effects of estrogen use on cardiovascular and cognitive function in postmenopausal women have been recently discredited, controversy remains regarding its usefulness for maintaining skeletal muscle mass or strength. Therefore, the purpose of this study was to

  10. Personality, function and satisfaction in patients undergoing total hip or knee replacement.

    Science.gov (United States)

    Ramaesh, Rishikesan; Jenkins, Paul; Lane, Judith V; Knight, Sara; Macdonald, Deborah; Howie, Colin

    2014-03-01

    The aim of this study was to investigate the relationships between personality and joint-specific function, general physical and general mental health in patients undergoing total hip (THA) and knee arthroplasty (TKA). One hundred and eighty-four patients undergoing THA and 205 undergoing TKA were assessed using the Eysneck Personality Questionnaire, brief version (EPQ-BV). General physical and mental health was measured using the Short-Form 12 (SF-12) questionnaire and the EuroQol (EQ-5D). Joint-specific function was measured using the Oxford hip or knee score. The "unstable introvert" personality type was associated with poorer pre-operative function and health in patients with hip arthrosis. In patients with knee arthrosis, there was poorer general health in those with "stable extrovert" and "unstable introvert" types. Personality was not an independent predictor of outcome following TKA or THA. The main predictor was pre-operative function and health. Comorbidity was an important covariate of both pre-operative and postoperative function. Personality may play a role in the interaction of these disease processes with function and health perception. It may also affect the response and interpretation of psychometric and patient-reported outcome measures. It may be important to characterise and identify these traits in potential arthroplasty patients as it may help deliver targeted education and management to improve outcomes in certain groups.

  11. Functional dissection of Streptococcus pyogenes M5 protein: the hypervariable region is essential for virulence.

    Directory of Open Access Journals (Sweden)

    Johan Waldemarsson

    Full Text Available The surface-localized M protein of Streptococcus pyogenes is a major virulence factor that inhibits phagocytosis, as determined ex vivo. Because little is known about the role of M protein in vivo we analyzed the contribution of different M protein regions to virulence, using the fibrinogen (Fg-binding M5 protein and a mouse model of acute invasive infection. This model was suitable, because M5 is required for mouse virulence and binds mouse and human Fg equally well, as shown here. Mixed infection experiments with wild type bacteria demonstrated that mutants lacking the N-terminal hypervariable region (HVR or the Fg-binding B-repeat region were strongly attenuated, while a mutant lacking the conserved C-repeats was only slightly attenuated. Because the HVR of M5 is not required for phagocytosis resistance, our data imply that this HVR plays a major but unknown role during acute infection. The B-repeat region is required for phagocytosis resistance and specifically binds Fg, suggesting that it promotes virulence by binding Fg. However, B-repeat mutants were attenuated even in Fg-deficient mice, implying that the B-repeats may have a second function, in addition to Fg-binding. These data demonstrate that two distinct M5 regions, including the HVR, are essential to virulence during the early stages of an infection. In particular, our data provide the first in vivo evidence that the HVR of an M protein plays a major role in virulence, focusing interest on the molecular role of this region.

  12. Forkhead box a2 (FOXA2) is essential for uterine function and fertility.

    Science.gov (United States)

    Kelleher, Andrew M; Peng, Wang; Pru, James K; Pru, Cindy A; DeMayo, Francesco J; Spencer, Thomas E

    2017-02-07

    Establishment of pregnancy is a critical event, and failure of embryo implantation and stromal decidualization in the uterus contribute to significant numbers of pregnancy losses in women. Glands of the uterus are essential for establishment of pregnancy in mice and likely in humans. Forkhead box a2 (FOXA2) is a transcription factor expressed specifically in the glands of the uterus and is a critical regulator of postnatal uterine gland differentiation in mice. In this study, we conditionally deleted FOXA2 in the adult mouse uterus using the lactotransferrin Cre (Ltf-Cre) model and in the neonatal mouse uterus using the progesterone receptor Cre (Pgr-Cre) model. The uteri of adult FOXA2-deleted mice were morphologically normal and contained glands, whereas the uteri of neonatal FOXA2-deleted mice were completely aglandular. Notably, adult FOXA2-deleted mice are completely infertile because of defects in blastocyst implantation and stromal cell decidualization. Leukemia inhibitory factor (LIF), a critical implantation factor of uterine gland origin, was not expressed during early pregnancy in adult FOXA2-deleted mice. Intriguingly, i.p. injections of LIF initiated blastocyst implantation in the uteri of both gland-containing and glandless adult FOXA2-deleted mice. Although pregnancy was rescued by LIF and was maintained to term in uterine gland-containing adult FOXA2-deleted mice, pregnancy failed by day 10 in neonatal FOXA2-deleted mice lacking uterine glands. These studies reveal a previously unrecognized role for FOXA2 in regulation of adult uterine function and fertility and provide original evidence that uterine glands and, by inference, their secretions play important roles in blastocyst implantation and stromal cell decidualization.

  13. Elucidation of the Synthetic Mechanism of Acylceramide, an Essential Lipid for Skin Barrier Function.

    Science.gov (United States)

    Ohno, Yusuke

    2017-01-01

    The primary function of the skin is to act as a permeability barrier that prevents water loss from inside the body and external invasion such as by pathogens, harmful substances, and allergens. Lipids play a critical role in skin barrier formation by forming multi-lamellar structures in the stratum corneum, the outermost cell layer of the epidermis. Ceramide, the backbone of sphingolipids, accounts for more than 50% of the stratum corneum lipids. Acylceramides are epidermis-specific ceramide species essential for skin barrier formation. Decreases in acylceramide levels and changes in ceramide composition and chain-length are associated with such cutaneous disorders as ichthyosis, atopic dermatitis, and psoriasis. Acylceramide consists of a long-chain base and an amide-linked ultra-long-chain fatty acid (ULCFA, 28-36 carbon chain), which is ω-hydroxylated and esterified with linoleic acid. Although the molecular mechanism by which acylceramide is generated has not been fully understood for decades, we recently identified two genes, CYP4F22 and PNPLA1, involved in acylceramide synthesis and elucidated the entire biosynthetic pathway of acylceramide: the synthesis of ULCFA by ELOVL1 and ELOVL4, ω-hydroxylation of the ULCFA by CYP4F22, amide-bond formation with a long-chain base by CERS3, and transacylation of linoleic acid from triacylglycerol to ω-hydroxyceramide by PNPLA1 to generate acylceramide. CYP4F22 and PNPLA1 are the causative genes of ichthyosis. We demonstrated that mutations of CYP4F22 or PNPLA1 markedly reduced acylceramide production. Our recent findings provide important insights into the molecular mechanisms of skin barrier formation and of ichthyosis pathogenesis.

  14. Kidney growth and renal functions under the growth hormone replacement therapy in children.

    Science.gov (United States)

    Ece, Aydın; Çetinkaya, Semra; Ekşioğlu, Seçil; Şenel, Saliha; Özkasap, Serdar; Giniş, Tayfur; Sen, Velat; Şahin, Cahit

    2014-05-01

    The aim of this study was to investigate the kidney growth and renal functions in children receiving recombinant human growth hormone (rhGH) treatment. A total of 37 children who received rhGH for 1.5 years before the study was started and 48 healthy controls were included at first evaluation. Hormone levels were determined and kidney sizes were measured by ultrasound. Kidney functions were assessed by serum creatinine and estimated glomerular filtration rate (eGFR). After 3 years of first evaluation, 23 patients were re-assessed. Kidney sizes were found to be lower in rhGH received children compared with controls at first evaluation (p0.05). Although no abnormal renal function test results were found at first and second evaluations; rhGH received children had significantly lower eGFR, at first evaluation, compared with controls; however, renal functions significantly increased after 3 years of follow-up (pgrowth is parallel to growth in body height and other visceral organs. A 3-years rhGH treatment resulted in significant increases in renal functions.

  15. Multiple essential MT1-MMP functions in tooth root formation, dentinogenesis, and tooth eruption.

    Science.gov (United States)

    Xu, H; Snider, T N; Wimer, H F; Yamada, S S; Yang, T; Holmbeck, K; Foster, B L

    2016-01-01

    Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a transmembrane zinc-endopeptidase that breaks down extracellular matrix components, including several collagens, during tissue development and physiological remodeling. MT1-MMP-deficient mice (MT1-MMP(-/-)) feature severe defects in connective tissues, such as impaired growth, osteopenia, fibrosis, and conspicuous loss of molar tooth eruption and root formation. In order to define the functions of MT1-MMP during root formation and tooth eruption, we analyzed the development of teeth and surrounding tissues in the absence of MT1-MMP. In situ hybridization showed that MT1-MMP was widely expressed in cells associated with teeth and surrounding connective tissues during development. Multiple defects in dentoalveolar tissues were associated with loss of MT1-MMP. Root formation was inhibited by defective structure and function of Hertwig's epithelial root sheath (HERS). However, no defect was found in creation of the eruption pathway, suggesting that tooth eruption was hampered by lack of alveolar bone modeling/remodeling coincident with reduced periodontal ligament (PDL) formation and integration with the alveolar bone. Additionally, we identified a significant defect in dentin formation and mineralization associated with the loss of MT1-MMP. To segregate these multiple defects and trace their cellular origin, conditional ablation of MT1-MMP was performed in epithelia and mesenchyme. Mice featuring selective loss of MT1-MMP activity in the epithelium were indistinguishable from wild type mice, and importantly, featured a normal HERS structure and molar eruption. In contrast, selective knock-out of MT1-MMP in Osterix-expressing mesenchymal cells, including osteoblasts and odontoblasts, recapitulated major defects from the global knock-out including altered HERS structure, short roots, defective dentin formation and mineralization, and reduced alveolar bone formation, although molars were able to erupt. These data

  16. Ankle replacement

    Science.gov (United States)

    Ankle arthroplasty - total; Total ankle arthroplasty; Endoprosthetic ankle replacement; Ankle surgery ... Ankle replacement surgery is most often done while you are under general anesthesia. This means you will ...

  17. Topology essentials

    CERN Document Server

    Milewski, Emil G

    2013-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Topology includes an overview of elementary set theory, relations and functions, ordinals and cardinals, topological spaces, continuous functions, metric spaces and normed spaces, co

  18. Measures of right ventricular function after transcatheter versus surgical aortic valve replacement

    DEFF Research Database (Denmark)

    Grønlykke, Lars; Ihlemann, Nikolaj; Ngo, Anh Thuc

    2017-01-01

    OBJECTIVES: Describe changes in measures of right ventricular (RV) function in patients treated for aortic stenosis using open-chest surgery (SAVR) or transcatheter treatment (TAVR). METHODS: Patients in the Nordic Aortic Valve Intervention (NOTION) trial were randomized 1:1 to TAVR (n = 114...

  19. PSYCHOSEXUAL FUNCTIONING IN WOMEN WITH COMPLETE TESTICULAR FEMINIZATION - IS ANDROGEN REPLACEMENT THERAPY PREFERABLE TO ESTROGEN

    NARCIS (Netherlands)

    SLOB, AK; TENBOSCH, JJ; VANHALL, EV; DEJONG, FH; SCHULTZ, WCMW; EIKELBOOM, FA

    1993-01-01

    Effects of oral testosterone undecanoate (Andriol) on blood hormone levels, moods, sociosexual functioning and self-image of the body were studied in four gonadectomized patients with complete testicular feminization. In a double-blind cross-over experiment, patients were treated with oral

  20. Comparative impact of AAV and enzyme replacement therapy on respiratory and cardiac function in adult Pompe mice

    Directory of Open Access Journals (Sweden)

    Darin J Falk

    Full Text Available Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA. Cardiac dysfunction and respiratory muscle weakness are primary features of this disorder. To attenuate the progressive and rapid accumulation of glycogen resulting in cardiorespiratory dysfunction, adult Gaa−/− mice were administered a single systemic injection of rAAV2/9-DES-hGAA (AAV9-DES or bimonthly injections of recombinant human GAA (enzyme replacement therapy (ERT. Assessment of cardiac function and morphology was measured 1 and 3 months after initiation of treatment while whole-body plethysmography and diaphragmatic contractile function was evaluated at 3 months post-treatment in all groups. Gaa−/− animals receiving either AAV9-DES or ERT demonstrated a significant improvement in cardiac function and diaphragmatic contractile function as compared to control animals. AAV9-DES treatment resulted in a significant reduction in cardiac dimension (end diastolic left ventricular mass/gram wet weight; EDMc at 3 months postinjection. Neither AAV nor ERT therapy altered minute ventilation during quiet breathing (eupnea. However, breathing frequency and expiratory time were significantly improved in AAV9-DES animals. These results indicate systemic delivery of either strategy improves cardiac function but AAV9-DES alone improves respiratory parameters at 3 months post-treatment in a murine model of Pompe disease.

  1. Long-term effects of growth hormone replacement therapy on thyroid function in adults with growth hormone deficiency.

    Science.gov (United States)

    Losa, Marco; Scavini, Marina; Gatti, Elisa; Rossini, Alessandro; Madaschi, Sara; Formenti, Ilaria; Caumo, Andrea; Stidley, Christine A; Lanzi, Roberto

    2008-12-01

    Clinical studies on the effect of growth hormone (GH) on thyroid function in patients with GH deficiency are contradictory. Further, the majority of published observations are limited to the first 6-12 months of GH replacement therapy. The aim of our study was to estimate the incidence of clinically relevant hypothyroidism in a cohort of patients with adult GH deficiency (AGHD) during long-term therapy with recombinant human GH (rhGH). The study was designed as a retrospective collection of data on thyroid function in 49 AGHD patients of whom 44 (90%) had multiple hormone deficiency. Thirty-seven patients (76%) were on stable levothyroxine (LT4) replacement therapy (HYPO), and 12 (24%) were euthyroid (EUT). Therapy with rhGH was started at a dose of 3.5 microg/kg body weight and adjusted according to insulin-like growth factor-I (IGF-I) levels. At baseline, 6 months, 12 months, and yearly thereafter we measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, and IGF-I. Study outcome was fT4 level below the normal range (9 pmol/L), irrespectively of fT3 or thyroid-stimulating hormone levels. During a follow-up of 115 patient-years, mean fT4 level decreased significantly, although remaining within the normal range (p = 0.0242; month 48 vs. baseline). The largest decrease was between baseline and month 6, when fT4 decreased of 1.43 pmol/L (95% confidence interval, 0.33-2.53) per 1 unit (microg/kg body weight) increase in rhGH dose. The incidence of hypothyroidism was 1.2 (HYPO group) and 6.7 (EUT group) events per 100 patient-years. We confirm that in patients with AGHD, rhGH therapy is associated with a small, although significant, decrement of fT4 in the first 6 months of replacement therapy. However, the incidence of hypothyroidism is low. Monitoring of thyroid function during rhGH therapy is advisable, particularly in the first year of therapy when the largest decrease in fT4 occurs.

  2. Taxonomically Restricted Genes with Essential Functions Frequently Play Roles in Chromosome Segregation inCaenorhabditis elegansandSaccharomyces cerevisiae.

    Science.gov (United States)

    Verster, Adrian J; Styles, Erin B; Mateo, Abigail; Derry, W Brent; Andrews, Brenda J; Fraser, Andrew G

    2017-10-05

    Genes encoding essential components of core cellular processes are typically highly conserved across eukaryotes. However, a small proportion of essential genes are highly taxonomically restricted; there appear to be no similar genes outside the genomes of highly related species. What are the functions of these poorly characterized taxonomically restricted genes (TRGs)? Systematic screens in Saccharomyces cerevisiae and Caenorhabditis elegans previously identified yeast or nematode TRGs that are essential for viability and we find that these genes share many molecular features, despite having no significant sequence similarity. Specifically, we find that those TRGs with essential phenotypes have an expression profile more similar to highly conserved genes, they have more protein-protein interactions and more protein disorder. Surprisingly, many TRGs play central roles in chromosome segregation; a core eukaryotic process. We thus find that genes that appear to be highly evolutionarily restricted do not necessarily play roles in species-specific biological functions but frequently play essential roles in core eukaryotic processes. Copyright © 2017 Verste et al.

  3. Combining functional and structural genomics to sample the essential Burkholderia structome.

    Directory of Open Access Journals (Sweden)

    Loren Baugh

    Full Text Available The genus Burkholderia includes pathogenic gram-negative bacteria that cause melioidosis, glanders, and pulmonary infections of patients with cancer and cystic fibrosis. Drug resistance has made development of new antimicrobials critical. Many approaches to discovering new antimicrobials, such as structure-based drug design and whole cell phenotypic screens followed by lead refinement, require high-resolution structures of proteins essential to the parasite.We experimentally identified 406 putative essential genes in B. thailandensis, a low-virulence species phylogenetically similar to B. pseudomallei, the causative agent of melioidosis, using saturation-level transposon mutagenesis and next-generation sequencing (Tn-seq. We selected 315 protein products of these genes based on structure-determination criteria, such as excluding very large and/or integral membrane proteins, and entered them into the Seattle Structural Genomics Center for Infection Disease (SSGCID structure determination pipeline. To maximize structural coverage of these targets, we applied an "ortholog rescue" strategy for those producing insoluble or difficult to crystallize proteins, resulting in the addition of 387 orthologs (or paralogs from seven other Burkholderia species into the SSGCID pipeline. This structural genomics approach yielded structures from 31 putative essential targets from B. thailandensis, and 25 orthologs from other Burkholderia species, yielding an overall structural coverage for 49 of the 406 essential gene families, with a total of 88 depositions into the Protein Data Bank. Of these, 25 proteins have properties of a potential antimicrobial drug target i.e., no close human homolog, part of an essential metabolic pathway, and a deep binding pocket. We describe the structures of several potential drug targets in detail.This collection of structures, solubility and experimental essentiality data provides a resource for development of drugs against

  4. Combining functional and structural genomics to sample the essential Burkholderia structome.

    Science.gov (United States)

    Baugh, Loren; Gallagher, Larry A; Patrapuvich, Rapatbhorn; Clifton, Matthew C; Gardberg, Anna S; Edwards, Thomas E; Armour, Brianna; Begley, Darren W; Dieterich, Shellie H; Dranow, David M; Abendroth, Jan; Fairman, James W; Fox, David; Staker, Bart L; Phan, Isabelle; Gillespie, Angela; Choi, Ryan; Nakazawa-Hewitt, Steve; Nguyen, Mary Trang; Napuli, Alberto; Barrett, Lynn; Buchko, Garry W; Stacy, Robin; Myler, Peter J; Stewart, Lance J; Manoil, Colin; Van Voorhis, Wesley C

    2013-01-01

    The genus Burkholderia includes pathogenic gram-negative bacteria that cause melioidosis, glanders, and pulmonary infections of patients with cancer and cystic fibrosis. Drug resistance has made development of new antimicrobials critical. Many approaches to discovering new antimicrobials, such as structure-based drug design and whole cell phenotypic screens followed by lead refinement, require high-resolution structures of proteins essential to the parasite. We experimentally identified 406 putative essential genes in B. thailandensis, a low-virulence species phylogenetically similar to B. pseudomallei, the causative agent of melioidosis, using saturation-level transposon mutagenesis and next-generation sequencing (Tn-seq). We selected 315 protein products of these genes based on structure-determination criteria, such as excluding very large and/or integral membrane proteins, and entered them into the Seattle Structural Genomics Center for Infection Disease (SSGCID) structure determination pipeline. To maximize structural coverage of these targets, we applied an "ortholog rescue" strategy for those producing insoluble or difficult to crystallize proteins, resulting in the addition of 387 orthologs (or paralogs) from seven other Burkholderia species into the SSGCID pipeline. This structural genomics approach yielded structures from 31 putative essential targets from B. thailandensis, and 25 orthologs from other Burkholderia species, yielding an overall structural coverage for 49 of the 406 essential gene families, with a total of 88 depositions into the Protein Data Bank. Of these, 25 proteins have properties of a potential antimicrobial drug target i.e., no close human homolog, part of an essential metabolic pathway, and a deep binding pocket. We describe the structures of several potential drug targets in detail. This collection of structures, solubility and experimental essentiality data provides a resource for development of drugs against infections and diseases

  5. The effect of posterior and lateral approach on patient-reported outcome measures and physical function in patients with osteoarthritis, undergoing total hip replacement

    DEFF Research Database (Denmark)

    Rosenlund, Signe; Broeng, Leif; Jensen, Carsten

    2014-01-01

    is a prospective, double blinded, parallel-group controlled trial with balanced randomisation [1: 1]. Patients with hip osteoarthritis scheduled for hip replacement surgery, aged 45-70 years, will be consecutively recruited and randomised into two groups. Group A will receive hip replacement using the posterior......BACKGROUND: Total hip replacement provides pain relief and improves physical function and quality of life in patients with end-stage hip osteoarthritis. The incidence of hip replacement operations is expected to increase due to the growing elderly population. Overall, the posterior approach...... and lateral approach are the two most commonly used approaches for hip replacement operations. The posterior approach is associated with an increased risk of revision due to dislocations, and some studies have shown that the lateral approach is associated with reduced patient-reported outcomes, including...

  6. Essential role of EBF1 in the generation and function of distinct mature B cell types

    OpenAIRE

    Vilagos, Bojan; Hoffmann, Mareike; Souabni, Abdallah; Sun, Qiong; Werner, Barbara; Medvedovic, Jasna; Bilic, Ivan; Minnich, Martina; Axelsson, Elin; Jaritz, Markus; Busslinger, Meinrad

    2012-01-01

    The transcription factor EBF1 is essential for lineage specification in early B cell development. In this study, we demonstrate by conditional mutagenesis that EBF1 is required for B cell commitment, pro–B cell development, and subsequent transition to the pre–B cell stage. Later in B cell development, EBF1 was essential for the generation and maintenance of several mature B cell types. Marginal zone and B-1 B cells were lost, whereas follicular (FO) and germinal center (GC) B cells were redu...

  7. Patterns of evolutionary conservation of essential genes correlate with their compensability.

    Directory of Open Access Journals (Sweden)

    Tobias Bergmiller

    2012-06-01

    Full Text Available Essential genes code for fundamental cellular functions required for the viability of an organism. For this reason, essential genes are often highly conserved across organisms. However, this is not always the case: orthologues of genes that are essential in one organism are sometimes not essential in other organisms or are absent from their genomes. This suggests that, in the course of evolution, essential genes can be rendered nonessential. How can a gene become non-essential? Here we used genetic manipulation to deplete the products of 26 different essential genes in Escherichia coli. This depletion results in a lethal phenotype, which could often be rescued by the overexpression of a non-homologous, non-essential gene, most likely through replacement of the essential function. We also show that, in a smaller number of cases, the essential genes can be fully deleted from the genome, suggesting that complete functional replacement is possible. Finally, we show that essential genes whose function can be replaced in the laboratory are more likely to be non-essential or not present in other taxa. These results are consistent with the notion that patterns of evolutionary conservation of essential genes are influenced by their compensability-that is, by how easily they can be functionally replaced, for example through increased expression of other genes.

  8. Total cervical disk replacement with a prestige LP® prosthesis: clinical and functional outcomes

    Directory of Open Access Journals (Sweden)

    Rafael Osório Rocha

    2014-01-01

    Full Text Available Objective: To determine the clinical and functional results of short- and medium-term cervical arthroplasty with the Prestige LP® prosthesis for the treatment of compressive myelopathy, radiculopathy and axial pain with radiculopathty. Methods: This retrospective study, conducted from 2009 to 2012, included 18 patients. Only 16 were found for the second stage of research, conducted in 2011 and 2012. Pre- and postoperative assessments were carried out using the CSOQ (Cervical Spine Outcomes Questionnaire. Odom criteria were used only in the postoperative evaluation. Both were translated and adapted to the local culture. Results: There was no postoperative radiculopathy or other complications requiring prolonged hospitalization. In most patients, there was a significant improvement in axial pain and radiculopathy, and there was only one indication of conversion to fusion. Conclusions: In selected cases of cervical degenerative disc disease, herniated cervical disc and compressive myeolopathy, cervical arthroplasty proved to be an effective and safe treatment in the short and medium terms.

  9. Cardiac function in growth hormone deficient patients before and after 1 year with replacement therapy: a magnetic resonance imaging study

    DEFF Research Database (Denmark)

    Andreassen, Mikkel; Faber, Jens Oscar; Kjær, Andreas

    2011-01-01

    Assessed by conventional echocardiography the influence of growth hormone deficiency (GHD) and effects of replacement therapy on left ventricle (LV) function and mass (LVM) have shown inconsistent results. We aimed to evaluate cardiac function before and during replacement therapy employing...... in LV systolic function or LVM occurred during 1 year of GH treatment. BNP levels were unchanged (P = 0.88), whereas NT-proBNP tended to decrease (P = 0.052). Assessed by the highly sensitive and precise CMRI method, untreated GHD was not associated with impaired systolic function or reduced LVMI and 1...... year of GH replacement using physiological doses did not influence cardiac mass or function....

  10. Influence of body mass index (BMI on functional improvements at 3 years following total knee replacement: a retrospective cohort study.

    Directory of Open Access Journals (Sweden)

    Paul Baker

    Full Text Available BACKGROUND: The number of patients presenting for total knee replacement who are classified as obese is increasing. The functional benefits of performing TKR in these patients are unclear. AIM: To assess the influence pre-operative body mass index has upon knee specific function, general health status and patient satisfaction at 3 years following total knee replacement. DESIGN: Retrospective comparative cohort study using prospectively collected data from an institutional arthroplasty register. METHODS: 1367 patients were assessed using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC and Medical Outcomes Trust Short Form-36 (SF-36 scores supplemented by a validated measure of satisfaction pre-operatively and subsequently at 1,2 and 3 year post-operatively. Comparisons were made by dividing the cohort into 4 groups based on body mass index (BMI 18.5-25.0 kg/m(2 (n = 253;>25.0-30.0 kg/m(2 (n = 559;>30.0-35.0 kg/m(2 (n = 373;>35.0 kg/m(2 (n = 182. RESULTS: Despite lower pre-operative, 1 and 3 year WOMAC and SF-36 scores patients with the highest BMIs >35.0 kg/m(2 experienced similar improvements to patients with a 'normal' BMI (18.5-25.0 kg/m(2 at 1 year (Difference in WOMAC improvement = 0.0 (95%CI -5.2 to 5.2, p = 1.00 and this improvement was sustained at up to 3 years (Difference in 1 year to 3 year improvement = 2.2 (95%CI: -2.1 to 6.5, p = 1.00. This effect was also observed for the SF-36 mental and physical component scores. Despite equivalent functional improvements levels of satisfaction in the >35.0 kg/m(2 group were lower than for any other BMI group (>35.0 kg/m(2 = 84.6% satisfied versus 18.5-5.0 kg/m(2 = 93.3% satisfied,p = 0.01 as was the proportion of patients who stated they would have the operation again (>35.0 kg/m(2 = 69.6% versus 18.5-25.0 kg/m(2 = 82.2%,p = 0.01. CONCLUSION: Obese and morbidly obese patients gain as much functional benefit from

  11. Functional Integrity of the Retrosplenial Cortex Is Essential for Rapid Consolidation and Recall of Fear Memory

    Science.gov (United States)

    Katche, Cynthia; Dorman, Guido; Slipczuk, Leandro; Cammarota, Martin; Medina, Jorge H.

    2013-01-01

    Memory storage is a temporally graded process involving different phases and different structures in the mammalian brain. Cortical plasticity is essential to store stable memories, but little is known regarding its involvement in memory processing. Here we show that fear memory consolidation requires early post-training macromolecular synthesis in…

  12. Functional replacement of the Saccharomyces cerevisiae fatty acid synthase with a bacterial type II system allows flexible product profiles.

    Science.gov (United States)

    Fernandez-Moya, Ruben; Leber, Christopher; Cardenas, Javier; Da Silva, Nancy A

    2015-12-01

    The native yeast type I fatty acid synthase (FAS) is a complex, rigid enzyme, and challenging to engineer for the production of medium- or short-chain fatty acids. Introduction of a type II FAS is a promising alternative as it allows expression control for each discrete enzyme and the addition of heterologous thioesterases. In this study, the native Saccharomyces cerevisiae FAS was functionally replaced by the Escherichia coli type II FAS (eFAS) system. The E. coli acpS + acpP (together), fabB, fabD, fabG, fabH, fabI, fabZ, and tesA were expressed in individual S. cerevisiae strains, and enzyme activity was confirmed by in vitro activity assays. Eight genes were then integrated into the yeast genome, while tesA or an alternate thioesterase gene, fatB from Ricinus communis or TEII from Rattus novergicus, was expressed from a multi-copy plasmid. Native FAS activity was eliminated by knocking out the yeast FAS2 gene. The strains expressing only the eFAS as de novo fatty acid source grew without fatty acid supplementation demonstrating that this type II FAS is able to functionally replace the native yeast FAS. The engineered strain expressing the R. communis fatB thioesterase increased total fatty acid titer 1.7-fold and shifted the fatty acid profile towards C14 production, increasing it from <1% in the native strain to more than 30% of total fatty acids, and reducing C18 production from 39% to 8%. © 2015 Wiley Periodicals, Inc.

  13. Endothelial Functioning and Hemodynamic Parameters in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement.

    Directory of Open Access Journals (Sweden)

    Cuixia Gao

    Full Text Available Subclinical hypothyroidism (SCH and its associations with atherosclerosis (AS and cardiovascular disease remain controversial. The purpose of our study was to observe changes in endothelial functioning and hemodynamics in rats with SCH and to determine whether L-thyroxine (L-T4 administration affects these changes.In total, sixty male Wistar rats were randomly divided into the following three groups with 20 rats each: control euthyroid rats, SCH rats and SCH rats that had been treated with thyroxine (SCH+T4. The SCH rats were induced by administration of 10 mg x kg(-1 x d(-1 methimazole (MMI once daily by gavage for 3 months. The SCH+T4 rats were administered the same dose of MMI for three months in addition to 2 μg x kg(-1 x d(-1 L-T4 once daily by gavage after 45 days of MMI administration. The control rats received physiological saline via gavage.The SCH group had significantly higher thyroid-stimulating hormone (TSH, total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, and endothelin (ET levels and a lower nitric oxide (NO level than the control and SCH+T4 groups. The tail and carotid artery blood pressures, left ventricular systolic pressure, heart rate and aorta ventralis blood flow were significantly lower in the SCH group than in the control and SCH+T4 groups. ACH treatment caused concentration-dependent relaxation, which was reduced in the SCH arteries compared with the control and SCH+T4 arteries. Histopathological examination revealed the absence of pathological changes in the SCH rat arteries.These findings demonstrate that L-T4 treatment ameliorates endothelial dysfunction and hemodynamic changes in SCH rats.

  14. Endothelial Functioning and Hemodynamic Parameters in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement

    Science.gov (United States)

    Liu, Jing; Guo, Qian; Tian, Limin

    2015-01-01

    Objective Subclinical hypothyroidism (SCH) and its associations with atherosclerosis (AS) and cardiovascular disease remain controversial. The purpose of our study was to observe changes in endothelial functioning and hemodynamics in rats with SCH and to determine whether L-thyroxine (L-T4) administration affects these changes. Methods In total, sixty male Wistar rats were randomly divided into the following three groups with 20 rats each: control euthyroid rats, SCH rats and SCH rats that had been treated with thyroxine (SCH+T4). The SCH rats were induced by administration of 10 mg.kg-1.d-1 methimazole (MMI) once daily by gavage for 3 months. The SCH+T4 rats were administered the same dose of MMI for three months in addition to 2 μg.kg-1.d-1 L-T4 once daily by gavage after 45 days of MMI administration. The control rats received physiological saline via gavage. Results The SCH group had significantly higher thyroid-stimulating hormone (TSH), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and endothelin (ET) levels and a lower nitric oxide (NO) level than the control and SCH+T4 groups. The tail and carotid artery blood pressures, left ventricular systolic pressure, heart rate and aorta ventralis blood flow were significantly lower in the SCH group than in the control and SCH+T4 groups. ACH treatment caused concentration-dependent relaxation, which was reduced in the SCH arteries compared with the control and SCH+T4 arteries. Histopathological examination revealed the absence of pathological changes in the SCH rat arteries. Conclusions These findings demonstrate that L-T4 treatment ameliorates endothelial dysfunction and hemodynamic changes in SCH rats. PMID:26158620

  15. GPHR-dependent functions of the golgi apparatus are essential for the formation of lamellar granules and the skin barrier

    OpenAIRE

    Tarutani, M; Nakajima, K; Uchida, Y; Takaishi, M; Goto-Inoue, N; Ikawa, M; Setou, M; Kinoshita, T; Elias, PM; Sano, S; Maeda, Y

    2012-01-01

    The lumen of the Golgi apparatus is regulated to be weakly acidic, which is critical for its functions. The Golgi pH regulator (GPHR) is an anion channel essential for normal acidification of the Golgi apparatus, and is therefore required for its functions. The Golgi apparatus has been thought to be the origin of lamellar granules in the skin. To study the functional role(s) of GPHR in the skin, we established keratinocyte-specific GPHR-knockout mice using the Cre-loxP system. These mutant mi...

  16. Genetic Characterization of Coenzyme A Biosynthesis Reveals Essential Distinctive Functions during Malaria Parasite Development in Blood and Mosquito

    Directory of Open Access Journals (Sweden)

    Robert J. Hart

    2017-06-01

    Full Text Available Coenzyme A (CoA is an essential universal cofactor for all prokaryotic and eukaryotic cells. In nearly all non-photosynthetic cells, CoA biosynthesis depends on the uptake and phosphorylation of vitamin B5 (pantothenic acid or pantothenate. Recently, putative pantothenate transporter (PAT and pantothenate kinases (PanKs were functionally characterized in P. yoelii. PAT and PanKs were shown to be dispensable for blood stage development, but they were essential for mosquito stages development. Yet, little is known about the cellular functions of the other enzymes of the CoA biosynthesis pathway in malaria parasite life cycle stages. All enzymes of this pathway were targeted for deletion or deletion/complementation analyses by knockout/knock-in plasmid constructs to reveal their essential roles in P. yoelii life cycle stages. The intermediate enzymes PPCS (Phosphopantothenylcysteine Synthase, PPCDC (Phosphopantothenylcysteine Decarboxylase were shown to be dispensable for asexual and sexual blood stage development, but they were essential for oocyst development and the production of sporozoites. However, the last two enzymes of this pathway, PPAT (Phosphopantetheine Adenylyltransferase and DPCK (Dephospho-CoA Kinase, were essential for blood stage development. These results indicate alternative first substrate requirement for the malaria parasite, other than the canonical pantothenate, for the synthesis of CoA in the blood but not inside the mosquito midgut. Collectively, our data shows that CoA de novo biosynthesis is essential for both blood and mosquito stages, and thus validates the enzymes of this pathway as potential antimalarial targets.

  17. Genetic Characterization of Coenzyme A Biosynthesis Reveals Essential Distinctive Functions during Malaria Parasite Development in Blood and Mosquito.

    Science.gov (United States)

    Hart, Robert J; Abraham, Amanah; Aly, Ahmed S I

    2017-01-01

    Coenzyme A (CoA) is an essential universal cofactor for all prokaryotic and eukaryotic cells. In nearly all non-photosynthetic cells, CoA biosynthesis depends on the uptake and phosphorylation of vitamin B5 (pantothenic acid or pantothenate). Recently, putative pantothenate transporter (PAT) and pantothenate kinases (PanKs) were functionally characterized in P. yoelii . PAT and PanKs were shown to be dispensable for blood stage development, but they were essential for mosquito stages development. Yet, little is known about the cellular functions of the other enzymes of the CoA biosynthesis pathway in malaria parasite life cycle stages. All enzymes of this pathway were targeted for deletion or deletion/complementation analyses by knockout/knock-in plasmid constructs to reveal their essential roles in P. yoelii life cycle stages. The intermediate enzymes PPCS (Phosphopantothenylcysteine Synthase), PPCDC (Phosphopantothenylcysteine Decarboxylase) were shown to be dispensable for asexual and sexual blood stage development, but they were essential for oocyst development and the production of sporozoites. However, the last two enzymes of this pathway, PPAT (Phosphopantetheine Adenylyltransferase) and DPCK (Dephospho-CoA Kinase), were essential for blood stage development. These results indicate alternative first substrate requirement for the malaria parasite, other than the canonical pantothenate, for the synthesis of CoA in the blood but not inside the mosquito midgut. Collectively, our data shows that CoA de novo biosynthesis is essential for both blood and mosquito stages, and thus validates the enzymes of this pathway as potential antimalarial targets.

  18. From essential to persistent genes: a functional approach to constructing synthetic life

    DEFF Research Database (Denmark)

    Acevedo-Rocha, Carlos G.; Fang, Gang; Schmidt, Markus

    2013-01-01

    A central undertaking in synthetic biology (SB) is the quest for the ‘minimal genome’. However, ‘minimal sets’ of essential genes are strongly context-dependent and, in all prokaryotic genomes sequenced to date, not a single protein-coding gene is entirely conserved. Furthermore, a lack of consen......A central undertaking in synthetic biology (SB) is the quest for the ‘minimal genome’. However, ‘minimal sets’ of essential genes are strongly context-dependent and, in all prokaryotic genomes sequenced to date, not a single protein-coding gene is entirely conserved. Furthermore, a lack...... for engineering cells and for creating cellular life-like forms in SB....

  19. Chitosan microencapsulation of various essential oils to enhance the functional properties of cotton fabric.

    Science.gov (United States)

    Javid, Amjed; Raza, Zulfiqar Ali; Hussain, Tanveer; Rehman, Asma

    2014-01-01

    The present study dealt with emulsive fabrication of chitosan microcapsules encapsulating essential oils in the present of bio/surfactant. The size distribution, morphology and stability of microcapsules were examined by using advanced surface characterisation techniques. At cetyl trimethyl ammonium bromide (CTAB) concentration of 330 mg/L, the smallest average size of microcapsules was observed as12.8 μm; whereas with biosurfactant at 50 mg/L, the microcapsules of smallest average size of 7.5 μm were observed. The fabricated microcapsules were applied on a desized, bleached and mercerised cotton fabric by using pad-dry-cure method by using a modified dihydroxy ethylene urea as a cross-linking agent. The cross-linking was confirmed by using scanning electron microscopy and Fourier transform infrared spectroscopy techniques. The antibacterial activity of finished fabric was evaluated using the turbidity estimation method. The stiffness and wrinkle recovery properties of the treated fabric were also investigated by using the standard methods. In general, antibacterial activity of treated fabric increased with the increase in chitosan and essential oil concentrations, whereas stiffness increased with increase in concentration of chitosan but decreased with increase in essential oil concentration.

  20. Developing Essential Understanding of Functions for Teaching Mathematics in Grades 9-12

    Science.gov (United States)

    Lloyd, Gwendolyn; Beckmann, Sybilla; Zbiek, Rose Mary; Cooney, Thomas

    2010-01-01

    Are sequences functions? What can't the popular "vertical line test" be applied in some cases to determine if a relation is a function? How does the idea of rate of change connect with simpler ideas about proportionality as well as more advanced topics in calculus? Helping high school students develop a robust understanding of functions requires…

  1. [Effect of enalapril maleate on vascular endothelial function and platelet-endothelial interactions in patients with essential hypertension].

    Science.gov (United States)

    Iakovlev, V M; Semenkin, A A; Iudin, S M; Nazarov, A G; Kudriashov, I L; Potapov, V V; Korennova, O Iu; Il'iunykh, L N

    2000-01-01

    Evaluation of endothelial function and platelet-endothelial interactions in patients with essential hypertension and dynamics of these changes in the course of treatment with enalapril maleate. The study included 37 patients with essential hypertension and 22 normotensive volunteers. 17 of hypertensive patients received enalapril maleate (enap, KRKA) 5-20 mg/day during the period of 1.5 months. The complex of investigations included: measurement of total plasma cholesteroi, 12-lead ECG, echocardiography, high-resolution ultrasound investigation of brachio-cephalic arteries, evaluation of flow-mediated dilation, measurement of von Willebrand's factor, spontaneous and induced platelet aggregation. Patients with essential hypertension exhibited higher levels of von Willebrand's factor in plasma and degree of spontaneous and induced platelet aggregation as well as lower responses of vessel wall to hemodynamic stimuli compared to normotensive healthy individuals. There was a strong correlation between endothelial function markers and CAD risk factors, elevation of platelet activity. Treatment with enalapril maleate led to a statistically significant decrease of von Willebrand's factor in plasma and ex vivo platelet aggregation whereas flow-mediated dilatation increased. Values of endothelial function markers and platelet activity approached to those of normotensive subjects and these changes were accompanied by a decrease of ECG signs of left ventricular hypertrophy. Patients with essential hypertension were found to have compromised endothelial function. However, the degree of endothelial dysfunction depends not on hemodynamic parameters, but on the cumulative effect of CAD risk factors. Treatment with enalapril maleate may lead to normalisation of endothelial function and decrease of platelet activity.

  2. Hip Replacement

    Science.gov (United States)

    Hip replacement is surgery for people with severe hip damage. The most common cause of damage is osteoarthritis. Osteoarthritis ... pain medicines, and exercise haven't helped, hip replacement surgery might be an option for you. During ...

  3. KARP-1 works as a heterodimer with Ku70, but the function of KARP-1 cannot perfectly replace that of Ku80 in DSB repair.

    Science.gov (United States)

    Koike, Manabu; Yutoku, Yasutomo; Koike, Aki

    2011-10-01

    Ku, the heterodimer of Ku70 and Ku80, plays an essential role in the DNA double-strand break (DSB) repair pathway, i.e., non-homologous end-joining (NHEJ). Two isoforms of Ku80 encoded by the same genes, namely, Ku80 and KARP-1 are expressed and function in primate cells, but not in rodent cells. Ku80 works as a heterodimer with Ku70. However, it is not yet clear whether KARP-1 forms a heterodimer with Ku70 and works as a heterodimer. Although KARP-1 appears to work in NHEJ, its physiological role remains unclear. In this study, we established and characterized EGFP-KARP-1-expressing xrs-6 cell lines, EGFP-KARP-1/xrs-6. We found that nuclear localization signal (NLS) of KARP-1 is localized in the C-terminal region. Our data showed that KARP-1 localizes within the nucleus in NLS-dependent and NLS-independent manner and forms a heterodimer with Ku70, and stabilizes Ku70. On the other hand, EGFP-KARP-1 could not perfectly complement the radiosensitivity and DSB repair activity of Ku80-deficient xrs-6 cells. Furthermore, KARP-1 could not accumulate at DSBs faster than Ku80, although EGFP-KARP-1 accumulates at DSBs. Our data demonstrate that the function of KARP-1 could not perfectly replace that of Ku80 in DSB repair, although KARP-1 has some biochemical properties, which resemble those of Ku80, and works as a heterodimer with Ku70. On the other hand, the number of EGFP-KARP-1-expressing xrs-6 cells showing pan-nuclear γ-H2AX staining significantly increases following X-irradiation, suggesting that KARP-1 may have a novel role in DSB response. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Asymmetric Microtubule Function Is an Essential Requirement for Polarized Organization of the Drosophila Bristle▿ †

    OpenAIRE

    Bitan, Amir; Guild, Gregory M.; Bar-Dubin, Dikla; Abdu, Uri

    2009-01-01

    While previous studies have shown that microtubules (MTs) are essential for maintaining the highly biased axial growth of the Drosophila bristle, the mechanism for this process has remained vague. We report that the MT minus-end marker, Nod-KHC, accumulates at the bristle tip, suggesting that the MT network in the bristle is organized minus end out. Potential markers for studying the importance of properly polarized MTs to bristle axial growth are Ik2 and Spindle-F (Spn-F), since mutations in...

  5. Conformational Flexibility Enables the Function of a BECN1 Region Essential for Starvation-Mediated Autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Mei, Yang; Ramanathan, Arvind; Glover, Karen; Stanley, Christopher; Sanishvili, Ruslan; Chakravarthy, Srinivas; Yang, Zhongyu; Colbert, Christopher L.; Sinha, Sangita C.

    2016-04-05

    BECN1 is essential for autophagy, a critical eukaryotic cellular homeostasis pathway. Here we delineate a highly conserved BECN1 domain located between previously characterized BH3 and coiled-coil domains and elucidate its structure and role in autophagy. The 2.0 angstrom sulfur-single-wavelength anomalous dispersion X-ray crystal structure of this domain demonstrates that its N-terminal half is unstructured while its C-terminal half is helical; hence, we name it the flexible helical domain (FHD). Circular dichroism spectroscopy, double electron electron resonance electron paramagnetic resonance, and small-angle X-ray scattering (SAXS) analyses confirm that the FHD is partially disordered, even in the context of adjacent BECN1 domains. Molecular dynamic simulations fitted to SAXS data indicate that the FHD transiently samples more helical conformations. FHD helicity increases in 2,2,2-trifluoroethanol, suggesting it may become more helical upon binding. Lastly, cellular studies show that conserved FHD residues are required for starvation-induced autophagy. Thus, the FHD likely undergoes a binding-associated disorder to-helix transition, and conserved residues critical for this interaction are essential for starvation-induced autophagy.

  6. Effect of prophylactic non-invasive mechanical ventilation on functional capacity after heart valve replacement: a clinical trial

    Directory of Open Access Journals (Sweden)

    Amaro Afrânio de Araújo-Filho

    Full Text Available OBJECTIVE: During cardiac surgery, several factors contribute to the development of postoperative pulmonary complications. Non-invasive ventilation is a promising therapeutic tool for improving the functionality of this type of patient. The aim of this study is to evaluate the functional capacity and length of stay of patients in a nosocomial intensive care unit who underwent prophylactic non-invasive ventilation after heart valve replacement. METHOD: The study was a controlled clinical trial, comprising 50 individuals of both sexes who were allocated by randomization into two groups with 25 patients in each group: the control group and experimental group. After surgery, the patients were transferred to the intensive care unit and then participated in standard physical therapy, which was provided to the experimental group after 3 applications of non-invasive ventilation within the first 26 hours after extubation. For non-invasive ventilation, the positive pressure was 10 cm H2O, with a duration of 1 hour. The evaluation was performed on the 7th postoperative day/discharge and included a 6-minute walk test. The intensive care unit and hospitalization times were monitored in both groups. Brazilian Registry of Clinical Trials (REBeC: RBR number 8bxdd3. RESULTS: Analysis of the 6-minute walk test showed that the control group walked an average distance of 264.34±76 meters and the experimental group walked an average distance of 334.07±71 meters (p=0.002. The intensive care unit and hospitalization times did not differ between the groups. CONCLUSION: Non-invasive ventilation as a therapeutic resource was effective toward improving functionality; however, non-invasive ventilation did not influence the intensive care unit or hospitalization times of the studied cardiac patients.

  7. Negative emotions affect postoperative scores for evaluating functional knee recovery and quality of life after total knee replacement

    Directory of Open Access Journals (Sweden)

    A. Qi

    2016-01-01

    Full Text Available This study aimed to determine whether psychological factors affect health-related quality of life (HRQL and recovery of knee function in total knee replacement (TKR patients. A total of 119 TKR patients (male: 38; female: 81 completed the Beck Anxiety Inventory (BAI, Beck Depression Inventory (BDI, State Trait Anxiety Inventory (STAI, Eysenck Personality Questionnaire-revised (EPQR-S, Knee Society Score (KSS, and HRQL (SF-36. At 1 and 6 months after surgery, anxiety, depression, and KSS scores in TKR patients were significantly better compared with those preoperatively (P<0.05. SF-36 scores at the sixth month after surgery were significantly improved compared with preoperative scores (P<0.001. Preoperative Physical Component Summary Scale (PCS and Mental Component Summary Scale (MCS scores were negatively associated with extraversion (E score (B=-0.986 and -0.967, respectively, both P<0.05. Postoperative PCS and State Anxiety Inventory (SAI scores were negatively associated with neuroticism (N score; B=-0.137 and -0.991, respectively, both P<0.05. Postoperative MCS, SAI, Trait Anxiety Inventory (TAI, and BAI scores were also negatively associated with the N score (B=-0.367, -0.107, -0.281, and -0.851, respectively, all P<0.05. The KSS function score at the sixth month after surgery was negatively associated with TAI and N scores (B=-0.315 and -0.532, respectively, both P<0.05, but positively associated with the E score (B=0.215, P<0.05. The postoperative KSS joint score was positively associated with postoperative PCS (B=0.356, P<0.05. In conclusion, for TKR patients, the scores used for evaluating recovery of knee function and HRQL after 6 months are inversely associated with the presence of negative emotions.

  8. NF-κB Essential MOdulator (NEMO) Is Critical for Thyroid Function

    OpenAIRE

    Reale, Carla; Iervolino, Anna; Scudiero, Ivan; Ferravante, Angela; Egildo D, Luca; Mazzone, Pellegrino; Zotti, Tiziana; Leonardi, Antonio; Roberto, Luca; Zannini, Mariastella; Cristofaro, Tiziana de; Shanmugakona, Muralitharan; Capasso, Giovambattista; Pasparakis, Manolis; Vito, Pasquale

    2016-01-01

    The I-?B kinase (IKK) subunit NEMO/IKK? (NEMO) is an adapter molecule that is critical for canonical activation of NF-?B, a pleiotropic transcription factor controlling immunity, differentiation, cell growth, tumorigenesis, and apoptosis. To explore the functional role of canonical NF-?B signaling in thyroid gland differentiation and function, we have generated a murine strain bearing a genetic deletion of the NEMO locus in thyroid. Here we show that thyrocyte-specific NEMO knock-out mice gra...

  9. Growth performance, liver and thyroid functions in buffalo calves reared on milk replacers supplemented with hydrogenated oils

    International Nuclear Information System (INIS)

    Abdelaal, A.E.; EL-Ashry, M.A.; Fekry, A.E.; Elwan, K.M.

    1991-01-01

    25 buffalo calves reared on natural milk (up to one week of age) were alloted to: A) controls: fed natural milk, and four experimental groups (B, C, D and E) constituting a 2 x 2 factorial design, where two brands (sultan and momtaz) and two levels (20% and 30% D M) of hydrogenated oils were added to skim milk-based replacers. Calf starter and hay were offered ad libitum with the liquid diets from the fourth week of age. Daily body gain and serum levels of : T 4 , T 3 , cholesterol, total proteins, albumin and the activities of transaminase (GOT and GPT) and alkaline phosphatase were determined at 3,6,9, and 12 weeks of age. The daily weight gain was significantly less in the groups receiving hydrogenated oils. However, feeding different brands and levels of hydrogenated oils added to skim milk caused significant decreases in the mean values of cholesterol, T 3 and T 4 and the T 4 /T 3 ratio. Addition of sultan oil to skim milk resulted in significant increases in serum levels of total proteins and globulins and significant decreases in A/G ratio, and both of GOT and alkaline phosphatase activities. The versed responses were noted in blood constituents and enzymatic activity when momtaz oil was added. The decrease in thyroid function and body weight gain is a clear observation shown in this study and needs further research

  10. Production and characterization of a functional Iranian white brined cheese by replacement of dairy fat with vegetable oils.

    Science.gov (United States)

    Achachlouei, B Fathi; Hesari, J; Damirchi, S Azadmard; Peighambardoust, Sh; Esmaiili, M; Alijani, S

    2013-10-01

    Full-fat cheese usually contains high amounts of saturated fatty acids and cholesterol, which may have negative health effects. In this study, full-fat white brined cheese, as a control sample, and experimental cheeses with olive and canola oils (T1, white brined cheese containing 50% canola oil, T2, white brined cheese containing 50% olive oil, T3, white brined cheese containing 100% canola oil and T4, white brined cheese containing 100% olive oil) were prepared from bovine milk. Physicochemical properties, lipolysis, proteolysis patterns and sensorial properties in the prepared samples were determined during 80 days of storage at 20-day intervals. Cheese incorporating vegetable oils showed lower amounts of saturated fatty acids and higher amounts of unsaturated fatty acids compared with the full-fat cheese (control) samples. Moisture, pH, lipolysis value, as assessed by the acid-degree value, and proteolysis values (pH 4.6 SN/TN% and NPN/TN%) significantly (p cheese incorporating with vegetable oils were different from those of full-fat cheese samples. White brined cheese containing olive and canola oils (100% fat substitution) received better sensory scores compared to other samples. The results showed that it is possible to replace dairy fat with olive and canola oils, which can lead to produce a new healthy and functional white brined cheese.

  11. Relation between preoperative autonomic function and blood pressure change after tourniquet deflation during total knee replacement arthroplasty.

    Science.gov (United States)

    Huh, In Young; Kim, Dae-Young; Lee, Ji-Hyeon; Shin, Soo Jin; Cho, Young Woo; Park, Soon Eun

    2012-02-01

    Tourniquets are used to provide a bloodless surgical field for extremities. Hypotension due to vasodilation and bleeding after tourniquet deflation is a common event. Hemodynamic stability is modulated by the autonomic nervous system (ANS). Heart rate variability (HRV) is a sensitive method for detecting individuals who may be at risk of hemodynamic instability during general anesthesia. The purpose of this study was to investigate ANS function to predict hypotension after tourniquet deflation. Eighty-six patients who underwent total knee replacement arthroplasty (TKRA) were studied. HRV, systolic blood pressure variability (SBPV) and baroreflex sensitivity (BRS) were analyzed. We assigned two groups depending on the lowest systolic blood pressure (SBP) or mean BP (MBP) after tourniquet release (Group H; SBP 80 mmHg and MBP > 60 mmHg). Fifteen patients developed severe hypotension and ten patients were treated with ephedrine. Of the parameters of HRV, SBPV, and BRS, only BRS(SEQ) was significant being low in Group H. BRS and high-frequency SBPV were correlated with the degree of MBP change after tourniquet deflation. Preoperative low BRS is associated with hypotension after tourniquet deflation, suggesting the importance of baroreflex regulation for intraoperative hemodynamic stability.

  12. Study on energy demand function of korea considering replacement among energy sources and the structural changes of demand behavior

    Energy Technology Data Exchange (ETDEWEB)

    Moon, C.K. [Korea Energy Economics Institute, Euiwang (Korea, Republic of)

    1997-08-01

    If the necessity of careful study on energy function is mentioned, it should be stressed that energy investment not only needs a long gestation period but also, acts as the bottleneck in the production capacity of an economy when investment is not enough. Thereby, the adverse effect of an energy supply shortage is very big. Especially, the replacement/supplemental relationship between energy and capital which corresponds to the movement on the iso-quanta curve is believed to have a direct relation with the answer as to whether long-term economic development would be possible under an energy crisis and its influence on technology selection. Furthermore, the advantages of technological advances which correspond to the movement on the iso-quanta curve has a direct relation with the question whether long-term economic development would be possible under an energy crisis depending on whether its direction is toward energy-saving or energy-consuming. This study tackles the main issues and outlines of the quantitative approach method based on the accounting approach method for modeling energy demand, quantitative economics approach method, and production model. In order to model energy demand of the Korean manufacturing industry, related data was established and a positive analytical model is completed and presented based on these. 122 refs., 10 tabs.

  13. GPHR-dependent functions of the Golgi apparatus are essential for the formation of lamellar granules and the skin barrier.

    Science.gov (United States)

    Tarutani, Masahito; Nakajima, Kimiko; Uchida, Yoshikazu; Takaishi, Mikiro; Goto-Inoue, Naoko; Ikawa, Masahito; Setou, Mitsutoshi; Kinoshita, Taroh; Elias, Peter M; Sano, Shigetoshi; Maeda, Yusuke

    2012-08-01

    The lumen of the Golgi apparatus is regulated to be weakly acidic, which is critical for its functions. The Golgi pH regulator (GPHR) is an anion channel essential for normal acidification of the Golgi apparatus, and is therefore required for its functions. The Golgi apparatus has been thought to be the origin of lamellar granules in the skin. To study the functional role(s) of GPHR in the skin, we established keratinocyte-specific GPHR-knockout mice using the Cre-loxP system. These mutant mice exhibited hypopigmented skin, hair loss, and scaliness. Histological examination of GPHR-knockout mice showed ballooning of the basal cells and follicular dysplasia. In addition, inflammatory cells were seen in the dermis. The expression of trans-Golgi network 46, a marker for lamellar bodies, and kallikrein 7, a protein within lamellar bodies, is diminished in GPHR-knockout mouse skin. Examination by electron microscopy revealed that keratinocytes produced aberrant lamellar bodies. The transepidermal water loss of these knockout mice was increased compared with wild-type mice. Moreover, expression of cathelicidin-related antimicrobial peptide (CRAMP) in the skin was diminished. These results suggest that GPHR is essential for the homeostasis of the epidermis including the formation of lamellar bodies and for the barrier function.

  14. [Clinical effect of arotinolol hydrochloride and its influence on renal function in elderly patients with essential hypertension].

    Science.gov (United States)

    Miyauchi, E; Matsumoto, M; Kimura, Y; Hattori, H; Tsukio, Y; Tsuchiya, H; Takasaki, M; Munehira, J; Yamada, K; Iwai, K; Kawanishi, K; Hoshino, T; Murai, H

    1999-08-01

    Arotinolol hydrochloride with alpha-and beta-receptor blocking action, developed in Japan, is mainly used for the treatment of hypertension. The study population consisted of 42 outpatients with essential hypertension with a blood pressure greater or equal to 160/96 mmHg. 10 men and 32 women, with a mean age of 77.5 year. The patients received 10 mg arotinolol hydrochloride daily for 24 weeks which was taken orally twice a day. We evaluated the changes of blood pressure, heart rate and chief complaints of patients before and every 4 weeks during treatment and the renal function before, 12 weeks after and 24 weeks after, the administration of arotinolol hydrochloride. Blood pressure and heart rate decreased significantly after 4 weeks of treatment with arotinolol hydrochloride (p arotinolol hydrochloride has antihypertensive effects without renal dysfunction in elderly patients with essential hypertension.

  15. Resumption of menstruation and pituitary response to gonadotropin-releasing hormone in functional hypothalamic amenorrhea subjects undertaking estrogen replacement therapy.

    Science.gov (United States)

    Shen, Z Q; Xu, J J; Lin, J F

    2013-11-01

    Functional hypothalamic amenorrhea (FHA) refers to a functional menstrual disorder with various causes and presentations. Recovery of menstrual cyclicity is common in long-term follow-up but the affecting factors remain unknown. To explore factors affecting the menstrual resumption and to evaluate the pituitary response to gonadotropin-releasing hormone (GnRH) in FHA. Thirty cases with FHA were recruited. All subjects were put on continuous 1 mg/day estradiol valerate orally and followed up monthly. Recovery was defined as the occurrence of at least three consecutive regular cycles. Responder referred to those who recovered within two years of therapy. Gonadotropin response to the 50 μg GnRH challenge was tested every three months. Nineteen (63.3%) subjects recovered with a mean time to recovery of 26.8 months. Time to recovery was negatively correlated with body mass index (BMI) before and by amenorrhea. Twentyone cases had undertaken therapy for more than two years and 10 of them recovered. BMI before and by amenorrhea were negatively correlated with the recovery. Significant increase of serum luteinizing hormone (LH) and LH response to GnRH were noted after recovery. Menstrual resumption was common in FHA undertaking estrogen replacement therapy (ERT). The likelihood of recovery was affected by their BMI before and by amenorrhea but not by the weight gain during therapy. Low serum LH and attenuated LH response to GnRH were the main features of pituitary deficiency in FHA. The menstrual resumption in FHA was accompanied by the recovery of serum LH and the LH response to GnRH.

  16. Health status, renal function, and quality of life after multiorgan failure and acute kidney injury requiring renal replacement therapy

    Directory of Open Access Journals (Sweden)

    Faulhaber-Walter R

    2016-05-01

    Full Text Available Robert Faulhaber-Walter,1,2 Sebastian Scholz,1,3 Herrmann Haller,1 Jan T Kielstein,1,* Carsten Hafer1,4,* 1Department of Renal and Hypertensive Disease, Medical School Hannover, Hannover, Germany; 2Facharztzentrum Aarberg, Waldshut-Tiengen, Germany; 3Sanitaetsversorgungszentrum Wunstorf, Wunstorf, Germany; 4HELIOS Klinikum Erfurt, Erfurt, Germany *These authors contributed equally to this work Background: Critically ill patients with acute kidney injury (AKI in need of renal replacement therapy (RRT may have a protracted and often incomplete rehabilitation. Their long-term outcome has rarely been investigated. Study design: Survivors of the HANnover Dialysis OUTcome (HANDOUT study were evaluated after 5 years for survival, health status, renal function, and quality of life (QoL. The HANDOUT study had examinded mortality and renal recovery of patients with AKI receiving either standard extendend or intensified dialysis after multi organ failure. Results: One hundred fifty-six former HANDOUT participants were analyzed. In-hospital mortality was 56.4%. Five-year survival after AKI/RRT was 40.1% (86.5% if discharged from hospital. Main causes of death were cardiovascular complications and sepsis. A total of 19 survivors presented to the outpatient department of our clinic and had good renal recovery (mean estimated glomerular filtration rate 72.5±30 mL/min/1.73 m2; mean proteinuria 89±84 mg/d. One person required maintenance dialysis. Seventy-nine percent of the patients had a pathological kidney sonomorphology. The Charlson comorbidity score was 2.2±1.4 and adjusted for age 3.3±2.1 years. Numbers of comorbid conditions averaged 2.38±1.72 per patient (heart failure [52%] > chronic kidney disease/myocardial infarction [each 29%]. Median 36-item short form health survey (SF-36™ index was 0.657 (0.69 physical health/0.66 mental health. Quality-adjusted life-years after 5 years were 3.365. Conclusion: Mortality after severe AKI is higher than

  17. The Paf oncogene is essential for hematopoietic stem cell function and development.

    Science.gov (United States)

    Amrani, Yacine M; Gill, Jonathan; Matevossian, Armine; Alonzo, Eric S; Yang, Chingwen; Shieh, Jae-Hung; Moore, Malcolm A; Park, Christopher Y; Sant'Angelo, Derek B; Denzin, Lisa K

    2011-08-29

    Hematopoietic stem cells (HSCs) self-renew to maintain the lifelong production of all blood populations. Here, we show that the proliferating cell nuclear antigen-associated factor (Paf) is highly expressed in cycling bone marrow HSCs and plays a critical role in hematopoiesis. Mice lacking Paf exhibited reduced bone marrow cellularity; reduced numbers of HSCs and committed progenitors; and leukopenia. These phenotypes are caused by a cell-intrinsic blockage in the development of long-term (LT)-HSCs into multipotent progenitors and preferential loss of lymphoid progenitors caused by markedly increased p53-mediated apoptosis. In addition, LT-HSCs from Paf(-/-) mice had increased levels of reactive oxygen species (ROS), failed to maintain quiescence, and were unable to support LT hematopoiesis. The loss of lymphoid progenitors was likely due the increased levels of ROS in LT-HSCs caused by treatment of Paf(-/-) mice with the anti-oxidant N-acetylcysteine restored lymphoid progenitor numbers to that of Paf(+/+) mice. Collectively, our studies identify Paf as a novel and essential regulator of early hematopoiesis. © 2011 Amrani et al.

  18. Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis.

    Science.gov (United States)

    Kümper, Sandra; Mardakheh, Faraz K; McCarthy, Afshan; Yeo, Maggie; Stamp, Gordon W; Paul, Angela; Worboys, Jonathan; Sadok, Amine; Jørgensen, Claus; Guichard, Sabrina; Marshall, Christopher J

    2016-01-14

    Rho-associated kinases 1 and 2 (ROCK1/2) are Rho-GTPase effectors that control key aspects of the actin cytoskeleton, but their role in proliferation and cancer initiation or progression is not known. Here, we provide evidence that ROCK1 and ROCK2 act redundantly to maintain actomyosin contractility and cell proliferation and that their loss leads to cell-cycle arrest and cellular senescence. This phenotype arises from down-regulation of the essential cell-cycle proteins CyclinA, CKS1 and CDK1. Accordingly, while the loss of either Rock1 or Rock2 had no negative impact on tumorigenesis in mouse models of non-small cell lung cancer and melanoma, loss of both blocked tumor formation, as no tumors arise in which both Rock1 and Rock2 have been genetically deleted. Our results reveal an indispensable role for ROCK, yet redundant role for isoforms 1 and 2, in cell cycle progression and tumorigenesis, possibly through the maintenance of cellular contractility.

  19. The Hip Functional Retrieval after Elective Surgery May Be Enhanced by Supplemented Essential Amino Acids

    Science.gov (United States)

    Baldissarro, Eleonora; Aquilani, Roberto; Boschi, Federica; Baiardi, Paola; Iadarola, Paolo; Fumagalli, Marco; Pasini, Evasio; Verri, Manuela; Dossena, Maurizia; Gambino, Arianna; Cammisuli, Sharon; Viglio, Simona

    2016-01-01

    It is not known whether postsurgery systemic inflammation and plasma amino acid abnormalities are still present during rehabilitation of individuals after elective hip arthroplasty (EHA). Sixty subjects (36 females; age 66.58 ± 8.37 years) were randomized to receive 14-day oral EAAs (8 g/day) or a placebo (maltodextrin). At admission to and discharge from the rehabilitation center, serum C-reactive protein (CRP) and venous plasma amino acid concentrations were determined. Post-EHA hip function was evaluated by Harris hip score (HHS) test. Ten matched healthy subjects served as controls. At baseline, all patients had high CRP levels, considerable reduction in several amino acids, and severely reduced hip function (HHS 40.78 ± 2.70 scores). After treatment, inflammation decreased both in the EAA group and in the placebo group. Only EAA patients significantly improved their levels of glycine, alanine, tyrosine, and total amino acids. In addition, they enhanced the rate of hip function recovery (HHS) (from baseline 41.8 ± 1.15 to 76.37 ± 6.6 versus baseline 39.78 ± 4.89 to 70.0 ± 7.1 in placebo one; p = 0.006). The study documents the persistence of inflammation and plasma amino acid abnormalities in post-EHA rehabilitation phase. EAAs enhance hip function retrieval and improve plasma amino acid abnormalities. PMID:27110573

  20. The Hip Functional Retrieval after Elective Surgery May Be Enhanced by Supplemented Essential Amino Acids

    Directory of Open Access Journals (Sweden)

    Eleonora Baldissarro

    2016-01-01

    Full Text Available It is not known whether postsurgery systemic inflammation and plasma amino acid abnormalities are still present during rehabilitation of individuals after elective hip arthroplasty (EHA. Sixty subjects (36 females; age 66.58±8.37 years were randomized to receive 14-day oral EAAs (8 g/day or a placebo (maltodextrin. At admission to and discharge from the rehabilitation center, serum C-reactive protein (CRP and venous plasma amino acid concentrations were determined. Post-EHA hip function was evaluated by Harris hip score (HHS test. Ten matched healthy subjects served as controls. At baseline, all patients had high CRP levels, considerable reduction in several amino acids, and severely reduced hip function (HHS 40.78±2.70 scores. After treatment, inflammation decreased both in the EAA group and in the placebo group. Only EAA patients significantly improved their levels of glycine, alanine, tyrosine, and total amino acids. In addition, they enhanced the rate of hip function recovery (HHS (from baseline 41.8±1.15 to 76.37±6.6 versus baseline 39.78±4.89 to 70.0±7.1 in placebo one; p=0.006. The study documents the persistence of inflammation and plasma amino acid abnormalities in post-EHA rehabilitation phase. EAAs enhance hip function retrieval and improve plasma amino acid abnormalities.

  1. Enriching Glucoraphanin in Brassica rapa Through Replacement of BrAOP2.2/BrAOP2.3 with Non-functional Genes

    Directory of Open Access Journals (Sweden)

    Zhiyuan Liu

    2017-08-01

    Full Text Available Sulforaphane, the hydrolytic product of glucoraphanin glucosinolate, is a potent anticarcinogen that reduces the risk of several human cancers. However, in most B. rapa vegetables, glucoraphanin is undetectable or only present in trace amounts, since the glucoraphanin that is present is converted to gluconapin by three functional BrAOP2 genes. In this study, to enrich beneficial glucoraphanin content in B. rapa, the functional BrAOP2 alleles were replaced by non-functional counterparts through marker-assisted backcrossing (MAB. We identified non-functional mutations of two BrAOP2 genes from B. rapa. The backcross progenies with introgression of both non-functional braop2.2 and braop2.3 alleles significantly increased the glucoraphanin content by 18 times relative to the recurrent parent. In contrast, replacement or introgression of single non-functional braop2.2 or braop2.3 locus did not change glucoraphanin content. Our results suggest that replacement of these two functional BrAOP2 genes with non-functional alleles has the potential for producing improved Brassica crops with enriched beneficial glucoraphanin content.

  2. miRNAs in chronic myeloid leukemia: small molecules, essential function.

    Science.gov (United States)

    Litwińska, Zofia; Machaliński, Bogusław

    2017-06-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with clonal expansion of cancerous bone marrow stem cells. Tyrosine kinase inhibitors (TKIs) targeting Bcr-Abl oncoprotein are the first-line therapy for most CML patients, however, some are unresponsive to it or develop resistance. Recently, microRNAs (miRNAs) have been implicated in the progression of CML and the development of TKI resistance based on their important regulatory function in cell homeostasis. MicroRNAs are small noncoding RNAs that post-transcriptionally regulate gene expression. Since microRNAs can function either as oncogenes or tumor suppressor genes in leukemogenesis, the potential of using them as therapeutic targets by inhibiting or amplifying their activity, opens up new opportunities for leukemia therapy. In this review, we focus on recent studies on the important roles of microRNAs in the pathogenesis of CML and their relevance as biomarkers for diagnosis, monitoring disease progression, and treatment response.

  3. Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells.

    Science.gov (United States)

    Sullivan, Lucas B; Gui, Dan Y; Hosios, Aaron M; Bush, Lauren N; Freinkman, Elizaveta; Vander Heiden, Matthew G

    2015-07-30

    Mitochondrial respiration is important for cell proliferation; however, the specific metabolic requirements fulfilled by respiration to support proliferation have not been defined. Here, we show that a major role of respiration in proliferating cells is to provide electron acceptors for aspartate synthesis. This finding is consistent with the observation that cells lacking a functional respiratory chain are auxotrophic for pyruvate, which serves as an exogenous electron acceptor. Further, the pyruvate requirement can be fulfilled with an alternative electron acceptor, alpha-ketobutyrate, which provides cells neither carbon nor ATP. Alpha-ketobutyrate restores proliferation when respiration is inhibited, suggesting that an alternative electron acceptor can substitute for respiration to support proliferation. We find that electron acceptors are limiting for producing aspartate, and supplying aspartate enables proliferation of respiration deficient cells in the absence of exogenous electron acceptors. Together, these data argue a major function of respiration in proliferating cells is to support aspartate synthesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Nuclear import and export signals are essential for proper cellular trafficking and function of ZIC3.

    Science.gov (United States)

    Bedard, James E J; Purnell, Jennifer D; Ware, Stephanie M

    2007-01-15

    Missense, frameshift and nonsense mutations in the zinc finger transcription factor ZIC3 cause heterotaxy as well as isolated congenital heart disease. Previously, we developed transactivation and subcellular localization assays to test the function of ZIC3 point mutations. Aberrant cytoplasmic localization suggested that the pathogenesis of ZIC3 mutations results, at least in part, from failure of appropriate cellular trafficking. To further investigate this hypothesis, the nucleocytoplasmic shuttling properties of ZIC3 have been examined. Subcellular localization assays designed to span the entire open-reading frame of wild-type and mutant ZIC3 proteins identified the presence of nucleocytoplasmic transport signals. ZIC3 domain mapping indicates that a relatively large region containing the zinc finger binding sites and a known GLI interacting domain is required for transport to the nucleus. Site-directed mutagenesis of critical residues within two putative nuclear localization signals (NLSs) leads to loss of nuclear localization. No further decrease was observed when both NLS sites were mutated, suggesting that mutation of either NLS site is sufficient for loss of importin-mediated nuclear localization. Additionally, we identify a cryptic CRM-1-dependent nuclear export signal (NES) within ZIC3, and identify a mutation within this region in a patient with heterotaxy. These results provide the first evidence that control of cellular trafficking of ZIC3 is critical for function and suggest a possible mechanism for transcriptional control during left-right patterning. Identification of mutations in mapped NLS or NES domains in heterotaxy patients demonstrates the functional importance of these domains in cardiac morphogenesis and allows for integration of structural analysis with developmental function.

  5. Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells

    OpenAIRE

    Sullivan, Lucas B.; Gui, Dan Y.; Hosios, Aaron M.; Bush, Lauren N.; Freinkman, Elizaveta; Vander Heiden, Matthew G.

    2015-01-01

    Mitochondrial respiration is important for cell proliferation, however the specific metabolic requirements fulfilled by respiration to support proliferation have not been defined. Here we show that a major role of respiration in proliferating cells is to provide electron acceptors for aspartate synthesis. This finding is consistent with the observation that cells lacking a functional respiratory chain are auxotrophic for pyruvate, which serves as an exogenous electron acceptor. Further, the p...

  6. High temperature is essential for preserved human sperm function during the devitrification process.

    Science.gov (United States)

    Mansilla, M A; Merino, O; Risopatrón, J; Isachenko, V; Isachenko, E; Sánchez, R

    2016-02-01

    Sperm vitrification is a cryopreservation method based on high-speed freezing by direct exposure of cells in liquid nitrogen (N2L), thereby avoiding the traditional cooling curves of freezing. The objective of this work was to determine the optimal warming temperature for vitrified human spermatozoa in order to maintain their fertilisation potential. Spermatozoa were cryopreserved by direct plunging into N2L and warmed at different temperatures for 5 and 10 s at 38, 40 and 42 °C. Sperm motility was evaluated by the CASA system and the sperm membrane function by HOST test. It was detected that progressive motility of sperm warmed at 38, 40 and 42 °C was 26.4 ± 8.4%; 56.6 ± 16.3% and 65.4 ± 15%, respectively, with statistically significant differences between the temperatures of 38 and 40 °C and 38 and 42 °C (P function evaluated by HOST test was better preserved at 42 °C (76.3 ± 2.0%) compared to 40 °C (43 ± 2%) and 38 °C (65.6 ± 1.5%). The temperature in the thawing process can affect the motility and plasma membrane integrity and function. The warming at 42 °C for thawed vitrified sperm is the optimum temperature to preserve the sperm physiological parameters. © 2015 Blackwell Verlag GmbH.

  7. Assessment of cognitive function in patients with essential hypertension treated with lercanidipine

    Directory of Open Access Journals (Sweden)

    J Tisaire-Sánchez

    2006-12-01

    Full Text Available J Tisaire-Sánchez1, J Roma2, Ignacio Camacho-Azcargorta3, J Bueno-Gómez1, J Mora-Maciá4, Angel Navarro51Fundación para la Investigación de la Hipertensión Arterial, Zaragoza, Spain; 2Fundació per l’Estudi de la Hipertensió Arterial als Hospitals Comarcals de Catalunya, Barcelona, Spain; 3Servicio de Cardiología, Clínica San José, Valencia, Spain; 4Unidad de Hipertensión Arterial, Instituto Médico Tecnológico, Barcelona, Spain; 5Recordati España, Madrid, SpainObjectives: The aim of this longitudinal, open-label, comparative, multicenter study was to assess cognitive function in hypertensive patients receiving mid-term treatment with lercanidipine.Methods: Hypertensive patients aged 40 years or older were treated with lercanidipine (10 mg daily after 7–10 days washout period. The duration of the study was 6 months. Blood pressure (BP was measured every 4 weeks (JNC 6th report. In patients with inadequate BP control, doxazosin was added and up-titrated. At baseline and after 6 months of treatment, cognitive function was evaluated using the Spanish validated version of the Mini-Mental State Examination (MMSE and the Trail Making Test (TMT. Results: In the study population of 467 patients, BP decreased from 154.4/95.3 mmHg at baseline to 134.8/80.7 mmHg at 6 months. At the end of the study, 98% of patients were receiving lercanidipine, 20% an angiotensin-converting enzyme inhibitor, and 6% doxazosin. Adequate BP control was obtained in 68% of patients. The mean (standard deviation MMSE scores improved from 32.35 (2.59 to 33.25 (2.36 (p<0.0001. Patients with good BP control scored significantly better than those with inadequate BP control (p<0.05, which was already observed at the first month. Conclusions: The third-generation calcium channel antagonist, lercanidipine, improved cognitive function after 6 months of treatment especially in patients with good BP control, suggesting that improvements in cognitive function may be

  8. Distinct regions of the Phytophthora essential effector Avh238 determine its function in cell death activation and plant immunity suppression.

    Science.gov (United States)

    Yang, Bo; Wang, Qunqing; Jing, Maofeng; Guo, Baodian; Wu, Jiawei; Wang, Haonan; Wang, Yang; Lin, Long; Wang, Yan; Ye, Wenwu; Dong, Suomeng; Wang, Yuanchao

    2017-04-01

    Phytophthora pathogens secrete effectors to manipulate host innate immunity, thus facilitating infection. Among the RXLR effectors highly induced during Phytophthora sojae infection, Avh238 not only contributes to pathogen virulence but also triggers plant cell death. However, the detailed molecular basis of Avh238 functions remains largely unknown. We mapped the regions responsible for Avh238 functions in pathogen virulence and plant cell death induction using a strategy that combines investigation of natural variation and large-scale mutagenesis assays. The correlation between cellular localization and Avh238 functions was also evaluated. We found that the 79 th residue (histidine or leucine) of Avh238 determined its cell death-inducing activity, and that the 53 amino acids in its C-terminal region are responsible for promoting Phytophthora infection. Transient expression of Avh238 in Nicotiana benthamiana revealed that nuclear localization is essential for triggering cell death, while Avh238-mediated suppression of INF1-triggered cell death requires cytoplasmic localization. Our results demonstrate that a representative example of an essential Phytophthora RXLR effector can evolve to escape recognition by the host by mutating one nucleotide site, and can also retain plant immunosuppressive activity to enhance pathogen virulence in planta. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  9. nanos function is essential for development and regeneration of planarian germ cells.

    Science.gov (United States)

    Wang, Yuying; Zayas, Ricardo M; Guo, Tingxia; Newmark, Phillip A

    2007-04-03

    Germ cells are required for the successful propagation of sexually reproducing species. Understanding the mechanisms by which these cells are specified and how their totipotency is established and maintained has important biomedical and evolutionary implications. Freshwater planarians serve as fascinating models for studying these questions. They can regenerate germ cells from fragments of adult tissues that lack reproductive structures, suggesting that inductive signaling is involved in planarian germ cell specification. To study the development and regeneration of planarian germ cells, we have functionally characterized an ortholog of nanos, a gene required for germ cell development in diverse organisms, from Schmidtea mediterranea. In the hermaphroditic strain of this species, Smed-nanos mRNA is detected in developing, regenerating, and mature ovaries and testes. However, it is not detected in the vast majority of newly hatched planarians or in small tissue fragments that will ultimately regenerate germ cells, consistent with an epigenetic origin of germ cells. We show that Smed-nanos RNA interference (RNAi) results in failure to develop, regenerate, or maintain gonads in sexual planarians. Unexpectedly, Smed-nanos mRNA is also detected in presumptive testes primordia of asexual individuals that reproduce strictly by fission. These presumptive germ cells are lost after Smed-nanos RNAi, suggesting that asexual planarians specify germ cells, but their differentiation is blocked downstream of Smed-nanos function. Our results reveal a conserved function of nanos in germ cell development in planarians and suggest that these animals will serve as useful models for dissecting the molecular basis of epigenetic germ cell specification.

  10. A SMN-Dependent U12 Splicing Event Essential for Motor Circuit Function

    Science.gov (United States)

    Lotti, Francesco; Imlach, Wendy L.; Saieva, Luciano; Beck, Erin S.; Hao, Le T.; Li, Darrick K.; Jiao, Wei; Mentis, George Z.; Beattie, Christine E.; McCabe, Brian D.; Pellizzoni, Livio

    2012-01-01

    SUMMARY Spinal muscular atrophy (SMA) is a motor neuron disease caused by deficiency of the ubiquitous survival motor neuron (SMN) protein. To define the mechanisms of selective neuronal dysfunction in SMA, we investigated the role of SMN-dependent U12 splicing events in the regulation of motor circuit activity. We show that SMN deficiency perturbs splicing and decreases the expression of a subset of U12 intron-containing genes in mammalian cells and Drosophila larvae. Analysis of these SMN target genes identifies Stasimon as a novel protein required for motor circuit function. Restoration of Stasimon expression in the motor circuit corrects defects in neuromuscular junction transmission and muscle growth in Drosophila SMN mutants and aberrant motor neuron development in SMN-deficient zebrafish. These findings directly link defective splicing of critical neuronal genes induced by SMN deficiency to motor circuit dysfunction, establishing a molecular framework for the selective pathology of SMA. PMID:23063131

  11. Positive selection neighboring functionally essential sites and disease-implicated regions of mammalian reproductive proteins

    Directory of Open Access Journals (Sweden)

    Harrison Alan J

    2010-02-01

    Full Text Available Abstract Background Reproductive proteins are central to the continuation of all mammalian species. The evolution of these proteins has been greatly influenced by environmental pressures induced by pathogens, rival sperm, sexual selection and sexual conflict. Positive selection has been demonstrated in many of these proteins with particular focus on primate lineages. However, the mammalia are a diverse group in terms of mating habits, population sizes and germ line generation times. We have examined the selective pressures at work on a number of novel reproductive proteins across a wide variety of mammalia. Results We show that selective pressures on reproductive proteins are highly varied. Of the 10 genes analyzed in detail, all contain signatures of positive selection either across specific sites or in specific lineages or a combination of both. Our analysis of SP56 and Col1a1 are entirely novel and the results show positively selected sites present in each gene. Our findings for the Col1a1 gene are suggestive of a link between positive selection and severe disease type. We find evidence in our dataset to suggest that interacting proteins are evolving in symphony: most likely to maintain interacting functionality. Conclusion Our in silico analyses show positively selected sites are occurring near catalytically important regions suggesting selective pressure to maximize efficient fertilization. In those cases where a mechanism of protein function is not fully understood, the sites presented here represent ideal candidates for mutational study. This work has highlighted the widespread rate heterogeneity in mutational rates across the mammalia and specifically has shown that the evolution of reproductive proteins is highly varied depending on the species and interacting partners. We have shown that positive selection and disease are closely linked in the Col1a1 gene.

  12. Positive selection neighboring functionally essential sites and disease-implicated regions of mammalian reproductive proteins.

    LENUS (Irish Health Repository)

    Morgan, Claire C

    2010-01-01

    ABSTRACT: BACKGROUND: Reproductive proteins are central to the continuation of all mammalian species. The evolution of these proteins has been greatly influenced by environmental pressures induced by pathogens, rival sperm, sexual selection and sexual conflict. Positive selection has been demonstrated in many of these proteins with particular focus on primate lineages. However, the mammalia are a diverse group in terms of mating habits, population sizes and germ line generation times. We have examined the selective pressures at work on a number of novel reproductive proteins across a wide variety of mammalia. RESULTS: We show that selective pressures on reproductive proteins are highly varied. Of the 10 genes analyzed in detail, all contain signatures of positive selection either across specific sites or in specific lineages or a combination of both. Our analysis of SP56 and Col1a1 are entirely novel and the results show positively selected sites present in each gene. Our findings for the Col1a1 gene are suggestive of a link between positive selection and severe disease type. We find evidence in our dataset to suggest that interacting proteins are evolving in symphony: most likely to maintain interacting functionality. CONCLUSION: Our in silico analyses show positively selected sites are occurring near catalytically important regions suggesting selective pressure to maximize efficient fertilization. In those cases where a mechanism of protein function is not fully understood, the sites presented here represent ideal candidates for mutational study. This work has highlighted the widespread rate heterogeneity in mutational rates across the mammalia and specifically has shown that the evolution of reproductive proteins is highly varied depending on the species and interacting partners. We have shown that positive selection and disease are closely linked in the Col1a1 gene.

  13. The yeast magmas ortholog pam16 has an essential function in fermentative growth that involves sphingolipid metabolism.

    Directory of Open Access Journals (Sweden)

    Mary K Short

    Full Text Available Magmas is a growth factor responsive gene encoding an essential mitochondrial protein in mammalian cells. Pam16, the Magmas ortholog in Saccharomyces cerevisiae, is a component of the presequence translocase-associated motor. A temperature-sensitive allele (pam16-I61N was used to query an array of non-essential gene-deletion strains for synthetic genetic interactions. The pam16-I61N mutation at ambient temperature caused synthetic lethal or sick phenotypes with genes involved in lipid metabolism, perixosome synthesis, histone deacetylation and mitochondrial protein import. The gene deletion array was also screened for suppressors of the pam16-I61N growth defect to identify compensatory pathways. Five suppressor genes were identified (SUR4, ISC1, IPT1, SKN1, and FEN1 and all are involved in sphingolipid metabolism. pam16-I61N cells cultured in glucose at non-permissive temperatures resulted in rapid growth inhibition and G1 cell cycle arrest, but cell viability was maintained. Altered mitochondria morphology, reduced peroxisome induction in glycerol/ethanol and oleate, and changes in the levels of several sphingolipids including C18 alpha-hydroxy-phytoceramide, were also observed in the temperature sensitive strain. Deletion of SUR4, the strongest suppressor, reversed the temperature sensitive fermentative growth defect, the morphological changes and the elevated levels of C18 alpha-hydroxy phytoceramide in pam16-I61N. Deletion of the other four suppressor genes had similar effects on C18 alpha-hydroxy-phytoceramide levels and restored proliferation to the pam16-I61N strain. In addition, pam16-I61N inhibited respiratory growth, likely by reducing cardiolipin, which is essential for mitochondrial function. Our results suggest that the pleiotropic effects caused by impaired Pam16/Magmas function are mediated in part by changes in lipid metabolism.

  14. Nuclear PTEN functions as an essential regulator of SRF-dependent transcription to control smooth muscle differentiation

    Science.gov (United States)

    Horita, Henrick; Wysoczynski, Christina L.; Walker, Lori A.; Moulton, Karen S.; Li, Marcella; Ostriker, Allison; Tucker, Rebecca; McKinsey, Timothy A.; Churchill, Mair E. A.; Nemenoff, Raphael A.; Weiser-Evans, Mary C. M.

    2016-01-01

    Vascular disease progression is associated with marked changes in vascular smooth muscle cell (SMC) phenotype and function. SMC contractile gene expression and, thus differentiation, is under direct transcriptional control by the transcription factor, serum response factor (SRF); however, the mechanisms dynamically regulating SMC phenotype are not fully defined. Here we report that the lipid and protein phosphatase, PTEN, has a novel role in the nucleus by functioning as an indispensible regulator with SRF to maintain the differentiated SM phenotype. PTEN interacts with the N-terminal domain of SRF and PTEN–SRF interaction promotes SRF binding to essential promoter elements in SM-specific genes. Factors inducing phenotypic switching promote loss of nuclear PTEN through nucleo-cytoplasmic translocation resulting in reduced myogenically active SRF, but enhanced SRF activity on target genes involved in proliferation. Overall decreased expression of PTEN was observed in intimal SMCs of human atherosclerotic lesions underlying the potential clinical importance of these findings. PMID:26940659

  15. Essential Function of Dicer in Resolving DNA Damage in the Rapidly Dividing Cells of the Developing and Malignant Cerebellum

    Directory of Open Access Journals (Sweden)

    Vijay Swahari

    2016-01-01

    Full Text Available Maintenance of genomic integrity is critical during neurodevelopment, particularly in rapidly dividing cerebellar granule neuronal precursors that experience constitutive replication-associated DNA damage. As Dicer was recently recognized to have an unexpected function in the DNA damage response, we examined whether Dicer was important for preserving genomic integrity in the developing brain. We report that deletion of Dicer in the developing mouse cerebellum resulted in the accumulation of DNA damage leading to cerebellar progenitor degeneration, which was rescued with p53 deficiency; deletion of DGCR8 also resulted in similar DNA damage and cerebellar degeneration. Dicer deficiency also resulted in DNA damage and death in other rapidly dividing cells including embryonic stem cells and the malignant cerebellar progenitors in a mouse model of medulloblastoma. Together, these results identify an essential function of Dicer in resolving the spontaneous DNA damage that occurs during the rapid proliferation of developmental progenitors and malignant cells.

  16. Evaluating Swallowing Muscles Essential for Hyolaryngeal Elevation by Using Muscle Functional Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Pearson, William G.; Hindson, David F.; Langmore, Susan E.; Zumwalt, Ann C.

    2013-01-01

    Purpose: Reduced hyolaryngeal elevation, a critical event in swallowing, is associated with radiation therapy. Two muscle groups that suspend the hyoid, larynx, and pharynx have been proposed to elevate the hyolaryngeal complex: the suprahyoid and longitudinal pharyngeal muscles. Thought to assist both groups is the thyrohyoid, a muscle intrinsic to the hyolaryngeal complex. Intensity modulated radiation therapy guidelines designed to preserve structures important to swallowing currently exclude the suprahyoid and thyrohyoid muscles. This study used muscle functional magnetic resonance imaging (mfMRI) in normal healthy adults to determine whether both muscle groups are active in swallowing and to test therapeutic exercises thought to be specific to hyolaryngeal elevation. Methods and Materials: mfMRI data were acquired from 11 healthy subjects before and after normal swallowing and after swallowing exercise regimens (the Mendelsohn maneuver and effortful pitch glide). Whole-muscle transverse relaxation time (T2 signal, measured in milliseconds) profiles of 7 test muscles were used to evaluate the physiologic response of each muscle to each condition. Changes in effect size (using the Cohen d measure) of whole-muscle T2 profiles were used to determine which muscles underlie swallowing and swallowing exercises. Results: Post-swallowing effect size changes (where a d value of >0.20 indicates significant activity during swallowing) for the T2 signal profile of the thyrohyoid was a d value of 0.09; a d value of 0.40 for the mylohyoid, 0.80 for the geniohyoid, 0.04 for the anterior digastric, and 0.25 for the posterior digastric-stylohyoid in the suprahyoid muscle group; and d values of 0.47 for the palatopharyngeus and 0.28 for the stylopharyngeus muscles in the longitudinal pharyngeal muscle group. The Mendelsohn maneuver and effortful pitch glide swallowing exercises showed significant effect size changes for all muscles tested, except for the thyrohyoid. Conclusions

  17. Essential function of the transcription factor Rax in the early patterning of the mammalian hypothalamus.

    Science.gov (United States)

    Orquera, Daniela P; Nasif, Sofia; Low, Malcolm J; Rubinstein, Marcelo; de Souza, Flávio S J

    2016-08-01

    The hypothalamus is a region of the anterior forebrain that controls basic aspects of vertebrate physiology, but the genes involved in its development are still poorly understood. Here, we investigate the function of the homeobox gene Rax/Rx in early hypothalamic development using a conditional targeted inactivation strategy in the mouse. We found that lack of Rax expression prior to embryonic day 8.5 (E8.5) caused a general underdevelopment of the hypothalamic neuroepithelium, while inactivation at later timepoints had little effect. The early absence of Rax impaired neurogenesis and prevented the expression of molecular markers of the dorsomedial hypothalamus, including neuropeptides Proopiomelanocortin and Somatostatin. Interestingly, the expression domains of genes expressed in the ventromedial hypothalamus and infundibulum invaded dorsal hypothalamic territory, showing that Rax is needed for the proper dorsoventral patterning of the developing medial hypothalamus. The phenotypes caused by the early loss of Rax are similar to those of eliminating the expression of the morphogen Sonic hedgehog (Shh) specifically from the hypothalamus. Consistent with this similarity in phenotypes, we observed that Shh and Rax are coexpressed in the rostral forebrain at late head fold stages and that loss of Rax caused a downregulation of Shh expression in the dorsomedial portion of the hypothalamus. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Structure and functional regulation of RipA, a mycobacterial enzyme essential for daughter cell separation.

    Science.gov (United States)

    Ruggiero, Alessia; Marasco, Daniela; Squeglia, Flavia; Soldini, Silvia; Pedone, Emilia; Pedone, Carlo; Berisio, Rita

    2010-09-08

    Cell separation depends on cell-wall hydrolases that cleave the peptidoglycan layer connecting daughter cells. In Mycobacterium tuberculosis, this process is governed by the predicted endopeptidase RipA. In the absence of this enzyme, the bacterium is unable to divide and exhibits an abnormal phenotype. We here report the crystal structure of a relevant portion of RipA, containing its catalytic-domain and an extra-domain of hitherto unknown function. The structure clearly demonstrates that RipA is produced as a zymogen, which needs to be activated to achieve cell-division. Bacterial cell-wall degradation assays and proteolysis experiments strongly suggest that activation occurs via proteolytic processing of a fully solvent exposed loop identified in the crystal structure. Indeed, proteolytic cleavage at this loop produces an activated form, consisting of the sole catalytic domain. Our work provides the first evidence of self-inhibition in cell-disconnecting enzymes and opens a field for the design of novel antitubercular therapeutics. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Metabolomics: An Essential Tool to Understand the Function of Peroxisome Proliferator–Activated Receptor Alpha

    Science.gov (United States)

    Montanez, Jessica E.; Peters, Jeffrey M.; Correll, Jared B.; Gonzalez, Frank J.; Patterson, Andrew D.

    2013-01-01

    The peroxisome proliferator–activated receptor (PPAR) family of nuclear hormone transcription factors (PPARα, PPARβ/δ, and PPARγ) is regulated by a wide array of ligands including natural and synthetic chemicals. PPARs have important roles in control of energy metabolism and are known to influence inflammation, differentiation, carcinogenesis, and chemical toxicity. As such, PPARs have been targeted as therapy for common disorders such as cancer, metabolic syndrome, obesity, and diabetes. The recent application of metabolomics, or the global, unbiased measurement of small molecules found in biofluids, or extracts from cells, tissues, or organisms, has advanced our understanding of the varied and important roles that the PPARs have in normal physiology as well as in pathophysiological processes. Continued development and refinement of analytical platforms, and the application of new bioinformatics strategies, have accelerated the widespread use of metabolomics and have allowed further integration of small molecules into systems biology. Recent studies using metabolomics to understand PPARα function, as well as to identify PPARα biomarkers associated with drug efficacy/toxicity and drug-induced liver injury, will be discussed. PMID:23197196

  20. DDR1 signaling is essential to sustain Stat5 function during lactogenesis.

    Science.gov (United States)

    Faraci-Orf, Elena; McFadden, Catherine; Vogel, Wolfgang F

    2006-01-01

    Postnatal development of the mammary gland is achieved by an interplay of endocrine and extracellular matrix-derived signals. Despite intense research, a comprehensive understanding of the temporal and spatial coordination of these hormonal and basement membrane stimuli is still lacking. Here, we address the role of the collagen-receptor DDR1 in integrating extracellular matrix-derived signaling with the lactogenic pathway initiated by the prolactin receptor. We found that stimulation of DDR1-overexpressing mammary epithelial HC11 cells with collagen and prolactin resulted in stronger and more sustained induction of Stat5 phosphorylation as compared to control cells. Enhanced Stat5 activity in HC11-DDR1 cells correlated with increased beta-casein gene expression. In contrast, cells derived from DDR1-null mice showed reduced Stat5 activation upon lactogenic stimulation and completely failed to induce beta-casein expression. The cell-autonomous role of DDR1 in controlling ductal branching and alveologenesis prior to the onset of lactogenesis was corroborated by mammary tissue transplantation experiments. Our results show that aside from hormone- and cytokine receptors, DDR1 signaling establishes a third matrix-derived pathway vital to maintain mammary gland function. (c) 2005 Wiley-Liss, Inc.

  1. Starfish ApDOCK protein essentially functions in larval defense system operated by mesenchyme cells.

    Science.gov (United States)

    Furukawa, Ryohei; Funabashi, Hiromi; Matsumoto, Midori; Kaneko, Hiroyuki

    2012-11-01

    In larvae of the starfish, Asterina pectinifera, mesenchyme cells operate in the defense system through various behaviors. We have investigated mesenchyme cell dynamics during the immune response by identifying ApDOCK, a new member of the DOCK180 superfamily protein. In 4-day-old bipinnaria larvae processed for morpholino oligonucleotide-mediated knockdown of ApDOCK, injection of inorganic foreign substances revealed that (1) mesenchyme cells fail to undergo either directed migration toward a large oil-droplet or persistent spreading on the oil-droplet after contact; (2) neither uptake of micro-beads nor cell-to-cell fusion on the large oil-droplet differed from that of mesenchyme cells from control larvae. Similar behaviors were also recorded in experiments where bacteria were injected. Under culture conditions, the expression level of ApDOCK mRNA was significantly associated with the immunological behavior of mesenchyme cells. Apparently, the mesenchyme cells from ApDOCK loss-of-function larvae exhibited insufficient lamellipodium formation via lack of fibrous form of actin organization at the leading edge. These results suggest that the migratory congregation and persistence of encapsulation of larval mesenchyme cells are intracellularly regulated by ApDOCK protein, and this regulation is associated with organization of cytoskeletal actin.

  2. Physicochemical and functional properties of micronized jincheng orange by-products (Citrus sinensis Osbeck) dietary fiber and its application as a fat replacer in yogurt.

    Science.gov (United States)

    Yi, Tian; Huang, Xingjian; Pan, Siyi; Wang, Lufeng

    2014-08-01

    Orange by-products from juice extraction are generally discarded or used in animal feed due to their low market value. However, orange by-products show potential as dietary fiber (DF) and fat replacers in products such as yogurt. This study assessed the benefits of using orange by-products in DF-enriched materials such as DF powders (OP) and micronized DF with ball-milling (MDF). The study also investigated the effects of adding different levels of OP and MDF on the quality of low-fat yogurt. Results show that MDF showed better physicochemical and functional properties than OP, and that 2% MDF as a fat replacer in yogurt retained most of the textural and sensory properties of full-fat yogurt. Therefore, this study showed that MDF is a promising alternative as a fat replacer in low-fat yogurt, without sacrificing good taste and other qualities of full-fat yogurt.

  3. COMMERCIAL ENTERPRISE: ESSENTIAL CHARACTERISTICS, FUNCTIONS, EMPHASIS IN GROUNDING STRATEGIES FOR POLICY DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Oleksandr BOZULENKO

    2014-06-01

    Full Text Available The article defines the objective reasons stipulating the substantial potential of commercial activity in Ukraine, which is characterized by increasing competition. Taking into account the results of scientists-economists’ research and other sources the essence and peculiarities of the characteristics of commercial enterprise are considered. The main functions of commercial enterprises: economic, industrial and technological, external economic, social are characterized. The determination of commercial enterprises by different characteristics depending on the factors of their operation is given. It is noted that recently on-store retailing as an alternative to commercial enterprise has been increasingly getting importance. The attention is focused on the need to take into consideration the aforementioned features and characteristics of commercial enterprise while developing strategy of its promising economic development using marketing techniques. The essence of the term “strategy” and the possibility of using different kinds of development strategies of commercial enterprise as a non-dated plan of specific activities covering a long period are considered. Operating, investing, market economic strategy, strategy of diversification and differentiation, often used in the activity of commercial enterprise are analyzed. It is proved that the development of such a strategy should be carried out taking into account the socioeconomic situation of the region in which commercial enterprise is located. The article highlights the features of the socio-economic development of Chernivtsi Oblast, changes which have recently occurred in the field of commercial activities. Current trends in the regional economy are defined. Based on the results of the development of trade in the studied region, it is conceptually shown that for a medium-term perspective the strategy for perspective economic development of commercial enterprise should be stabilizing

  4. Comparative, validity and responsiveness of the HOOS-PS and KOOS-PS to the WOMAC physical function subscale in total joint replacement for osteoarthritis

    DEFF Research Database (Denmark)

    Davis, A M; Perruccio, A V; Canizares, M

    2009-01-01

    OBJECTIVE: To evaluate the internal consistency of the Hip disability and Osteoarthritis Outcome Score-Physical Function Short-form (HOOS-PS) and the Knee injury and Osteoarthritis Outcome Score-Physical Function Short-form (KOOS-PS) in total hip replacement (THR) and total knee (TKR) replacement....... Construct validity and responsiveness were compared to the Western Ontario McMaster Universities' Osteoarthritis Index (WOMAC) Likert 3.0 physical function (PF) subscale and the PF excluding the items in the short measures (PF-exclusions). METHODS: Participants completed the full HOOS or KOOS, measures...... and PF-exclusions with fatigue, CPG, anxiety and depression and HOOS/KOOS pain scales would differ by magnitudes of response means (SRMs) were calculated for the HOOS-PS, KOOS-PS, PF and PF-exclusions and hypothesized to be >1. RESULTS: The THR group (n=201) had a mean age of 62...

  5. Knee joint replacement

    Science.gov (United States)

    Total knee replacement; Knee arthroplasty; Knee replacement - total; Tricompartmental knee replacement; Subvastus knee replacement; Knee replacement - minimally invasive; Knee arthroplasty - minimally ...

  6. Plasmodium falciparum CENH3 is able to functionally complement Cse4p and its, C-terminus is essential for centromere function.

    Science.gov (United States)

    Verma, Garima; Surolia, Namita

    2013-01-01

    The Plasmodium falciparum centromeric histone variant PfCENH3 has been shown to occupy a 4-4.5 kb region on each chromosome, but the experimental demonstration of its structure-function relationship remains unexplored. By functional complementation assays, we report that the C-terminus, specifically the CATD region within the HFD of PfCENH3 is essential in centromere function. Our studies also indicate that the PfCENH3 specific LLAL residues of the CATD region are required for centromere targeting and chromosome segregation. Histone H3 of P. falciparum is not found to complement Cse4p (the yeast homologue of CENH3). We also report the identification of PfCENP-C, another component of the inner kinetochore protein complex and its association with PfCENH3. These studies thus delineate the structural determinants of PfCENH3. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Replacing penalties

    Directory of Open Access Journals (Sweden)

    Vitaly Stepashin

    2017-01-01

    Full Text Available УДК 343.24The subject. The article deals with the problem of the use of "substitute" penalties.The purpose of the article is to identify criminal and legal criteria for: selecting the replacement punishment; proportionality replacement leave punishment to others (the formalization of replacement; actually increasing the punishment (worsening of legal situation of the convicted.Methodology.The author uses the method of analysis and synthesis, formal legal method.Results. Replacing the punishment more severe as a result of malicious evasion from serving accused designated penalty requires the optimization of the following areas: 1 the selection of a substitute punishment; 2 replacement of proportionality is serving a sentence other (formalization of replacement; 3 ensuring the actual toughening penalties (deterioration of the legal status of the convict. It is important that the first two requirements pro-vide savings of repression in the implementation of the replacement of one form of punishment to others.Replacement of punishment on their own do not have any specifics. However, it is necessary to compare them with the contents of the punishment, which the convict from serving maliciously evaded. First, substitute the punishment should assume a more significant range of restrictions and deprivation of certain rights of the convict. Second, the perfor-mance characteristics of order substitute the punishment should assume guarantee imple-mentation of the new measures.With regard to replacing all forms of punishment are set significant limitations in the application that, in some cases, eliminates the possibility of replacement of the sentence, from serving where there has been willful evasion, a stricter measure of state coercion. It is important in the context of the topic and the possibility of a sentence of imprisonment as a substitute punishment in cases where the original purpose of the strict measures excluded. It is noteworthy that the

  8. Therapeutic validity and effectiveness of preoperative exercise on functional recovery after joint replacement: a systematic review and meta-analysis.

    NARCIS (Netherlands)

    Hoogeboom, T.J.; Oosting, E.; Vriezekolk, J.E.; Veenhof, C.; Siemonsma, P.C.; Bie, R.A. de; Ende, C.H.M. van den; Meeteren, N.L.U. van

    2012-01-01

    Background: Our aim was to develop a rating scale to assess the therapeutic validity of therapeutic exercise programmes. By use of this rating scale we investigated the therapeutic validity of therapeutic exercise in patients awaiting primary total joint replacement (TJR). Finally, we studied the

  9. [Severe diarrhea after the original well-functioning percutaneous endoscopic gastrostomy tube was replaced by a Mic-Key button].

    Science.gov (United States)

    Jensen, Susanne Wigh; Eriksen, Jan; Kristensen, Kurt

    2006-03-06

    We report two cases of colocutaneous fistula as a complication of percutaneous endoscopic gastrostomy (PEG) in small children. Both children developed severe osmotic diarrhoea immediately after the original PEG tube was replaced by a Mic-Key button which subsequently migrated to the colon.

  10. The structure of human SFPQ reveals a coiled-coil mediated polymer essential for functional aggregation in gene regulation

    Science.gov (United States)

    Lee, Mihwa; Sadowska, Agata; Bekere, Indra; Ho, Diwei; Gully, Benjamin S.; Lu, Yanling; Iyer, K. Swaminathan; Trewhella, Jill; Fox, Archa H.; Bond, Charles S.

    2015-01-01

    SFPQ, (a.k.a. PSF), is a human tumor suppressor protein that regulates many important functions in the cell nucleus including coordination of long non-coding RNA molecules into nuclear bodies. Here we describe the first crystal structures of Splicing Factor Proline and Glutamine Rich (SFPQ), revealing structural similarity to the related PSPC1/NONO heterodimer and a strikingly extended structure (over 265 Å long) formed by an unusual anti-parallel coiled-coil that results in an infinite linear polymer of SFPQ dimers within the crystals. Small-angle X-ray scattering and transmission electron microscopy experiments show that polymerization is reversible in solution and can be templated by DNA. We demonstrate that the ability to polymerize is essential for the cellular functions of SFPQ: disruptive mutation of the coiled-coil interaction motif results in SFPQ mislocalization, reduced formation of nuclear bodies, abrogated molecular interactions and deficient transcriptional regulation. The coiled-coil interaction motif thus provides a molecular explanation for the functional aggregation of SFPQ that directs its role in regulating many aspects of cellular nucleic acid metabolism. PMID:25765647

  11. The conserved WW-domain binding sites in Dystroglycan C-terminus are essential but partially redundant for Dystroglycan function

    Directory of Open Access Journals (Sweden)

    Deng W-M

    2009-02-01

    Full Text Available Abstract Background Dystroglycan (Dg is a transmembrane protein that is a part of the Dystrophin Glycoprotein Complex (DGC which connects the extracellular matrix to the actin cytoskeleton. The C-terminal end of Dg contains a number of putative SH3, SH2 and WW domain binding sites. The most C-terminal PPXY motif has been established as a binding site for Dystrophin (Dys WW-domain. However, our previous studies indicate that both Dystroglycan PPXY motives, WWbsI and WWbsII can bind Dystrophin protein in vitro. Results We now find that both WW binding sites are important for maintaining full Dg function in the establishment of oocyte polarity in Drosophila. If either WW binding site is mutated, the Dg protein can still be active. However, simultaneous mutations in both WW binding sites abolish the Dg activities in both overexpression and loss-of-function oocyte polarity assays in vivo. Additionally, sequence comparisons of WW binding sites in 12 species of Drosophila, as well as in humans, reveal a high level of conservation. This preservation throughout evolution supports the idea that both WW binding sites are functionally required. Conclusion Based on the obtained results we propose that the presence of the two WW binding sites in Dystroglycan secures the essential interaction between Dg and Dys and might further provide additional regulation for the cytoskeletal interactions of this complex.

  12. Pak2 is essential for the function of Foxp3+ regulatory T cells through maintaining a suppressive Treg phenotype.

    Science.gov (United States)

    O'Hagan, Kyle L; Miller, Stephen D; Phee, Hyewon

    2017-12-06

    Foxp3, a key transcription factor that drives lineage differentiation of regulatory T cells (Tregs), was thought to imprint a unique and irreversible genetic signature within Tregs. Recent evidence, however, suggests that loss or attenuation of Foxp3 expression can cause Tregs to de-differentiate into effector T cells capable of producing proinflammatory cytokines. Herein, we report that the signaling kinase, p21-activated kinase 2 (Pak2), is essential for maintaining Treg stability and suppressive function. Loss of Pak2, specifically in Tregs, resulted in reduced expression of multiple Treg functional molecules, including Foxp3, CD25, Nrp-1 and CTLA-4, coupled with a loss of Treg suppressive function in vitro and in vivo. Interestingly, Pak2-deficient Tregs gained expression of Th2-associated cytokines and the transcription factor, Gata3, becoming Th2-like cells, explaining their inability to regulate immune responses. Collectively, these findings suggest Pak2 as an important signaling molecule for guarding against aberrant immune responses through regulating the stability of Foxp3 + Tregs and maintaining a suppressive Treg phenotype.

  13. Role of measurement of cystatin C in analyzing the results of renal function tests in patients with essential hypertension

    International Nuclear Information System (INIS)

    Zhang Xiaofeng; Lu Hongtai; Dong Yaorong; Xia Jing; Liu Yi

    2003-01-01

    Objective: To explore the use of cystatin C for analysing the results of renal function tests and renal blood flow study in patients with essential hypertension. Methods: The following tests were performed in 62 patients with essential hypertension and 32 controls: plasma cystatin C (with LPET), plasma ET (with RIA), four urinary sensitive parameters for detecting early renal injury i.e. urinary Alb/Cr, NAG/Cr and α-mG/Cr (with ELISA) and renal blood flow study (with Doppler). Results: The patients could be divided into two groups: Cystatin C positive (above normal value, n=23) and cystamin C negative (n=39). Plasma ET levels in cystamin C positive group were significantly higher than those in the 32 controls. Values of the four urinary parameters in the two patient groups were very significantly higher than those in the controls (p<0.01), the difference between the two patient groups was also very significant (p<0.01). Renal arterial blood flow in the two patient groups was much different from that was no significant difference between the two groups themselves. In the patients, with the decrease of GFR, Serum creatinine levels were elevated but urea nitrogen levels remained within normal limit. Conclusion: In the cystamin C negative patients, there was already marked alteration of the renal blood flow through auto-regulation. Although GFR, serum creatinine and urea nitrogen levels remained within normal range, early renal injury, especially tubular ones had been present. As the disease worsened and cystatin levels increased, there was no progressive alteration of renal blood flow. Marked deterioration of renal glomeruli and tubular functions could be detected

  14. Ulk1-mediated autophagy plays an essential role in mitochondrial remodeling and functional regeneration of skeletal muscle.

    Science.gov (United States)

    Call, Jarrod A; Wilson, Rebecca J; Laker, Rhianna C; Zhang, Mei; Kundu, Mondira; Yan, Zhen

    2017-06-01

    Autophagy is a conserved cellular process for degrading aggregate proteins and dysfunctional organelle. It is still debatable if autophagy and mitophagy (a specific process of autophagy of mitochondria) play important roles in myogenic differentiation and functional regeneration of skeletal muscle. We tested the hypothesis that autophagy is critical for functional regeneration of skeletal muscle. We first observed time-dependent increases (3- to 6-fold) of autophagy-related proteins (Atgs), including Ulk1, Beclin1, and LC3, along with reduced p62 expression during C2C12 differentiation, suggesting increased autophagy capacity and flux during myogenic differentiation. We then used cardiotoxin (Ctx) or ischemia-reperfusion (I/R) to induce muscle injury and regeneration and observed increases in Atgs between days 2 and 7 in adult skeletal muscle followed by increased autophagy flux after day 7 Since Ulk1 has been shown to be essential for mitophagy, we asked if Ulk1 is critical for functional regeneration in skeletal muscle. We subjected skeletal muscle-specific Ulk1 knockout mice (MKO) to Ctx or I/R. MKO mice had significantly impaired recovery of muscle strength and mitochondrial protein content post-Ctx or I/R. Imaging analysis showed that MKO mice have significantly attenuated recovery of mitochondrial network at 7 and 14 days post-Ctx. These findings suggest that increased autophagy protein and flux occur during muscle regeneration and Ulk1-mediated mitophagy is critical for recovery for the mitochondrial network and hence functional regeneration. Copyright © 2017 the American Physiological Society.

  15. Targeted disruption of cubilin reveals essential developmental roles in the structure and function of endoderm and in somite formation

    Directory of Open Access Journals (Sweden)

    Cooley Marion A

    2006-06-01

    Full Text Available Abstract Background Cubilin is a peripheral membrane protein that interacts with the integral membrane proteins megalin and amnionless to mediate ligand endocytosis by absorptive epithelia such as the extraembryonic visceral endoderm (VE. Results Here we report the effects of the genetic deletion of cubilin on mouse embryonic development. Cubilin gene deletion is homozygous embryonic lethal with death occurring between 7.5–13.5 days post coitum (dpc. Cubilin-deficient embryos display developmental retardation and do not advance morphologically beyond the gross appearance of wild-type 8–8.5 dpc embryos. While mesodermal structures such as the allantois and the heart are formed in cubilin mutants, other mesoderm-derived tissues are anomalous or absent. Yolk sac blood islands are formed in cubilin mutants but are unusually large, and the yolk sac blood vessels fail to undergo remodeling. Furthermore, somite formation does not occur in cubilin mutants. Morphological abnormalities of endoderm occur in cubilin mutants and include a stratified epithelium in place of the normally simple columnar VE epithelium and a stratified cuboidal epithelium in place of the normally simple squamous epithelium of the definitive endoderm. Cubilin-deficient VE is also functionally defective, unable to mediate uptake of maternally derived high-density lipoprotein (HDL. Conclusion In summary, cubilin is required for embryonic development and is essential for the formation of somites, definitive endoderm and VE and for the absorptive function of VE including the process of maternal-embryo transport of HDL.

  16. Mission essential fitness: comparison of functional circuit training to traditional Army physical training for active duty military.

    Science.gov (United States)

    Heinrich, Katie M; Spencer, Vincent; Fehl, Nathanael; Poston, Walker S Carlos

    2012-10-01

    Appropriate and effective physical fitness training is imperative for soldier survival and mission success. The purpose of this study was to determine the effects of Mission Essential Fitness (MEF) circuit-style training program compared to standard Army Physical Readiness Training (APRT) on fitness, physiological, and body composition changes. Active duty Army personnel were randomly assigned to two groups (MEF = 34 or APRT = 33) for 8 weeks of training (15 sessions each). The MEF program included functional movements focused on strength, power, speed, and agility. Fifteen exercises were performed continuously for 60 to 90 seconds for 45 minutes. Baseline and post-test measures included the Army physical fitness test, physiological indicators, body composition, and additional fitness indicators. One-way analysis of covariance models indicated that MEF participants significantly increased their push-ups (p = 0.033), bench press (p = 0.001), and flexibility (p = 0.003) and significantly decreased their 2-mile run (p = 0.003) and step test heart rate (p = 0.004) compared to participants doing APRT. Both groups maintained body composition (p > 0.05) and reported no injuries. The MEF training program safely improved muscular strength and endurance, cardiovascular endurance, and flexibility, supporting functional fitness circuit-style exercise training for military personnel.

  17. Regulation of translation in haloarchaea: 5'- and 3'-UTRs are essential and have to functionally interact in vivo.

    Directory of Open Access Journals (Sweden)

    Mariam Brenneis

    Full Text Available Recently a first genome-wide analysis of translational regulation using prokaryotic species had been performed which revealed that regulation of translational efficiency plays an important role in haloarchaea. In fact, the fractions of genes under differential growth phase-dependent translational control in the two species Halobacterium salinarum and Haloferax volcanii were as high as in eukaryotes. However, nothing is known about the mechanisms of translational regulation in archaea. Therefore, two genes exhibiting opposing directions of regulation were selected to unravel the importance of untranslated regions (UTRs for differential translational control in vivo.Differential translational regulation in exponentially growing versus stationary phase cells was studied by comparing translational efficiencies using a reporter gene system. Translational regulation was not observed when 5'-UTRs or 3'-UTRs alone were fused to the reporter gene. However, their simultaneous presence was sufficient to transfer differential translational control from the native transcript to the reporter transcript. This was true for both directions of translational control. Translational regulation was completely abolished when stem loops in the 5'-UTR were changed by mutagenesis. An "UTR-swap" experiment demonstrated that the direction of translational regulation is encoded in the 3'-UTR, not in the 5'-UTR. While much is known about 5'-UTR-dependent translational control in bacteria, the reported findings provide the first examples that both 5'- and 3'-UTRs are essential and sufficient to drive differential translational regulation in a prokaryote and therefore have to functionally interact in vivo. The current results indicate that 3'-UTR-dependent translational control had already evolved before capping and polyadenylation of transcripts were invented, which are essential for circularization of transcripts in eukaryotes.

  18. Knee Replacement

    Science.gov (United States)

    ... days. Medications prescribed by your doctor should help control pain. During the hospital stay, you'll be encouraged to move your ... exercise your new knee. After you leave the hospital, you'll continue physical ... mobility and a better quality of life. And most knee replacements can be ...

  19. The impact of age on the postoperative response of the diastolic function and left ventricular mass regression after surgical or transcatheter aortic valve replacement for severe aortic stenosis.

    Science.gov (United States)

    Nakamura, Teruya; Toda, Koichi; Kuratani, Toru; Miyagawa, Shigeru; Yoshikawa, Yasushi; Fukushima, Satsuki; Saito, Shunsuke; Sawa, Yoshiki

    2017-06-01

    We examined the impact of advanced age on left ventricular mass regression and the change in the diastolic function after aortic valve replacement in patients with aortic stenosis. The present study included 129 patients who underwent either surgical or transcatheter aortic valve replacement and 1-year postoperative echocardiography. The patient characteristics and echocardiographic findings were compared between patients who were regression was significantly greater (p = 0.02) and diastolic dysfunction was less prevalent in group Y (p = 0.02) in comparison to group O. The change in E/e' was significantly correlated with the left ventricular mass regression in group Y (p = 0.02), but not in Group O (p = 0.21). The patients in group O were less susceptible to improvements in myocardial remodeling and the diastolic function in comparison to those in group Y. The altered physiological response to aortic valve replacement might help to determine the appropriate timing of surgery in elderly patients.

  20. Effect of Taohongsiwu decoction after total hip replacement on blood coagulation function, pain degree as well as RANKL and OPG content

    Directory of Open Access Journals (Sweden)

    Zhao-Xia Lu

    2016-11-01

    Full Text Available Objective: To analyze the effect of Taohongsiwu decoction after total hip replacement on blood coagulation function, pain degree as well as RANKL and OPG content. Methods: A total of 118 patients who underwent total hip replacement were divided into observation group and control group, and serum blood coagulation indexes, fibrinolysis indexes, pain mediators and inflammatory mediators as well as RANKL and OPG content were compared between two groups of patients 12 d after operation. Results: Blood coagulation indexes PT, APTT and TT levels of observation group 12 d after operation were greater than those of control group while D-D content was lower than that of control group; fibrinolysis indexes FIB, FDP, PAI-1 and t-PA content in serum were lower than those of control group while Plg and u-PA content were higher than those of control group; pain mediators β-EP, NO, CGRP, SP and PGE2 content in serum were lower than those of control group; inflammatory mediators hs-CRP, IL-6, TNF-α, IL-17, IL-33 and TREM-1 content in serum were lower than those of control group; RANKL and OPG content in serum were lower than those of control group. Conclusions: Taohongsiwu decoction can optimize patients’ blood coagulation function and reduce the perception of pain after total hip replacement, and is also of positive significance in promoting patients’ long-term fracture healing.

  1. Androgen receptor gene CAG repeat polymorphism independently influences recovery of male sexual function after testosterone replacement therapy in postsurgical hypogonadotropic hypogonadism.

    Science.gov (United States)

    Tirabassi, Giacomo; Delli Muti, Nicola; Corona, Giovanni; Maggi, Mario; Balercia, Giancarlo

    2014-05-01

    Few and contradictory studies have evaluated the possible influence of androgen receptor (AR) gene CAG repeat polymorphism on male sexual function. In this study we evaluated the role of AR gene CAG repeat polymorphism in the recovery of sexual function after testosterone replacement therapy (TRT) in men affected by postsurgical hypogonadotropic hypogonadism, a condition which is often associated with hypopituitarism and in which the sexual benefits of TRT must be distinguished from those of pituitary-function replacement therapies. Fifteen men affected by postsurgical hypogonadotropic hypogonadism were retrospectively assessed before and after TRT. Main outcome measures included sexual parameters as assessed by the International Index of Erectile Function questionnaire, levels of pituitary dependent hormones (total testosterone, free T3, free T4, cortisol, insulin-like growth factor-1 [IGF-1], prolactin), and results of genetic analysis (AR gene CAG repeat number). Plasma concentrations of free T3, free T4, cortisol, and prolactin did not vary significantly between the two phases, while testosterone and IGF-1 increased significantly after TRT. A significant improvement in all sexual parameters studied was found. The number of CAG triplets was negatively and significantly correlated with changes in all the sexual parameters, while opposite correlations were found between changes in sexual parameters and changes in testosterone levels; no correlation of change in IGF1 with change in sexual parameters was reported. On multiple linear regression analysis, after correction for changes in testosterone, nearly all the associations between the number of CAG triplets and changes in sexual parameters were confirmed. Shorter length AR gene CAG repeat number is associated with the recovery of sexual function after TRT in postsurgical male hypogonadotropic hypogonadism, independently of the effects of concomitant pituitary-replacement therapies. © 2014 International Society

  2. Mild-to-moderate functional tricuspid regurgitation in patients undergoing valve replacement for rheumatic mitral disease: the influence of tricuspid valve repair on clinical and echocardiographic outcomes.

    Science.gov (United States)

    Kim, Joon Bum; Yoo, Dong Gon; Kim, Gwan Sic; Song, Hyun; Jung, Sung-Ho; Choo, Suk Jung; Chung, Cheol Hyun; Lee, Jae Won

    2012-01-01

    The decision to repair mild-to-moderate functional tricuspid regurgitation (TR) during left-side heart surgery remains controversial. Objectives To avoid heterogeneity in patient population, patients with TR undergoing isolated mechanical mitral valve (MV) replacement for rheumatic mitral diseases were evaluated. Between 1997 and 2009, 236 patients with mild-to-moderate functional TR underwent first-time isolated mechanical MV replacement for rheumatic mitral diseases with (n=123; repair group) or without (n=113; non-repair group) tricuspid valve (TV) repair. Survival, valve-related complications, and TV function in these two groups were compared after adjustment for baseline characteristics using inverse-probability-of-treatment weighting. Follow-up was complete in 225 patients (95.3%) with a median follow-up of 48.7 months (IQR 20.2-89.5 months), during which time 991 echocardiographic assessments were done. Freedom from moderate-to-severe TR at 5 years was 92.9±2.9% in the repair group and 60.8±6.9% in the non-repair group (ptricuspid reoperation (HR=0.10, p=0.080) and congestive heart failure (HR=1.12, p=0.87). Postoperative moderate-to-severe TR was an independent predictor of poorer event-free survival (HR=2.90, p=0.038). These findings support the strategy of correcting mild-to-moderate functional TR at the time of MV replacement to maintain TV function and improve clinical outcomes.

  3. Functional Ability Improved in Essential Tremor by IncobotulinumtoxinA Injections Using Kinematically Determined Biomechanical Patterns – A New Future

    Science.gov (United States)

    Samotus, Olivia; Rahimi, Fariborz; Lee, Jack; Jog, Mandar

    2016-01-01

    Objective Effective treatment for functional disability caused by essential tremor is a significant unmet need faced by many clinicians today. Current literature regarding focal therapy by botulinum toxin type A (BoNT-A) injections uses fixed dosing regimens, which cannot be individualized, provides only limited functional benefit and unacceptable muscle weakness commonly occurs. This 38-week open label study, the longest to-date, demonstrates how kinematic technology addressed all these issues by guiding muscle selection. Method Participants (n = 24) were assessed at weeks 0, 6, 16, 22, 32, and 38 and injected with incobotulinumtoxinA at weeks 0, 16, and 32. Clinical assessments including UPDRS tremor items, Fahn-Tolosa-Marin (FTM) tremor rating scale assessing tremor severity, writing and functional ability, quality of life questionnaire (QUEST) and objective kinematic assessments were completed at every visit. Participants performed two postural and two weight-bearing scripted tasks with motion sensors placed over the wrist, elbow and shoulder joints. These sensors captured angular tremor amplitude (RMS units) and acceleration joint motion that was segmented into directional components: flexion-extension (F/E), pronation-supination and radial-ulnar at the wrist, F/E at the elbow, and F/E and adduction-abduction at the shoulder. Injection parameters were determined using kinematics, followed by the clinician’s determination of which muscles would contribute to the specific upper limb tremor biomechanics and dosing per participant. Results Multi-joint biomechanical recordings allowed individualized muscle selection and showed significant improvement in whole-arm function, FTM parts A-C scores, at week 6 which continued throughout the study. By week 38, the total FTM score statistically significantly reduced from 16.2±4.6 at week 0 to 9.5±6.3 (ptremor was significantly reduced from 2.6±0.5 at week 0 to 1.6±1.1 (p = 0.01) at week 32. Quality of life (QUEST

  4. Self-care essential extras: an integration of holistic nursing, functional medicine, and health coaching to promote therapeutic lifestyle change and decrease chronic disease.

    Science.gov (United States)

    Scattergood, Donna M

    2010-01-01

    The Essential Vitality Program blends holistic nursing, functional medicine, and health coaching to promote lifestyle changes that modify risk factors of costly chronic disease. Karl is a client who experienced enhanced vitality, decreased chronic pain and medications use, and improved meaningful functioning, by partnering with a holistic nurse coach.

  5. [Effects of r-hGH replacement therapy on glucose and lipid metabolism and thyroid function in children with idiopathic short stature].

    Science.gov (United States)

    Zheng, Fang-Yuan; Wang, Xue-Mei; Wang, Xin-Li

    2014-12-01

    To study the effects of recombinant human growth hormone (r-hGH) replacement therapy on glucose and lipid metabolism and thyroid function in children with idiopathic short stature (ISS). Forty-seven ISS children with a mean age of 10±3 years treated between January 2009 and January 2013 were enrolled. All children underwent r-hGH replacement therapy for 3-24 months and were followed up once every 3 months. Fasting blood glucose (FBG), insulin (INS), blood lipids and thyroid function were measured before treatment and after 0-1 and 1-2 years of treatment. After treatment with r-hGH, there were no significant changes in FBG, INS, insulin sensitivity index (ISI), and FBG/INS ratio (FGIR), but the FGIR showed a declining trend. The percentage of patients with FGIRhGH treatment, but there were no significant changes in total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and BMI. Furthermore, no significant change in thyroid function was observed after r-hGH therapy. r-hGH therapy can improve lipid metabolism, without significant impacts on thyroid function, FBG and INS. It seems to be a safe and reliable therapy for children with ISS. However, this therapy possibly reduces insulin sensitivity.

  6. Digalactosyldiacylglycerol is essential in Synechococcus elongatus PCC 7942, but its function does not depend on its biosynthetic pathway.

    Science.gov (United States)

    Maida, Eri; Awai, Koichiro

    2016-09-01

    Digalactosyldiacylglycerol (DGDG) is a major component of thylakoid membranes, occupying approximately 20% of the membrane system. This lipid composition is conserved from cyanobacteria to the chloroplasts of terrestrial plants, suggesting that DGDG is important for the function of photosynthetic membranes. Here we isolated the gene for DGDG synthase in the cyanobacterium Synechococcus elongatus PCC 7942 (7942dgdA) and found that this gene is essential for this species. 7942dgdA could be knocked out only when genes for cyanobacterial or plant DGDG synthases were expressed, indicating that the important factor was not the specific synthetic pathway but the lipid product. Lack of DGDG could not be compensated by the other membrane lipids in S. elongatus PCC 7942 or by glucosylgalactosyldiacylglycerol synthesized by the β-GlcT gene of Chloroflexus aurantiacus. These results reveal that DGDG has an indispensable role in S. elongatus PCC 7942 and that the second galactose molecule is key. Conservation and distribution of the galactolipid synthetic pathway among oxygenic phototrophs is discussed. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Cognitive functions, fatigue, depression, anxiety, and sleep disturbances: assessment of nonmotor features in young patients with essential tremor.

    Science.gov (United States)

    Sengul, Yildizhan; Sengul, Hakan S; Yucekaya, Sevda K; Yucel, Selma; Bakim, Bahadir; Pazarcı, Nevin K; Özdemir, Gökhan

    2015-09-01

    There is a growing amount of evidence to suggest that besides motor features, patients with essential tremor (ET) may exhibit significant nonmotor features, such as mild cognitive deficits, fatigue, neuropsychiatric symptoms, and sleep disturbances. The goal of this study was to examine nonmotor features in young patients with ET and their impact on quality of life. 45 patients (24.55 ± 7.16 years old) with ET and 35 controls were evaluated using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Beck Depression Inventory, Beck Anxiety Scale, Fatigue Severity Scale, and Short Form-36. Cognitive functions were evaluated using the Turkish version of the Montreal Cognitive Assessment Battery (MoCA). We ruled out other possible causes of the tremor. The tremor rate was evaluated using the Fahn-Tolosa-Marin Tremor Rating Scale. Poor sleep quality, fatigue, anxiety, and depressive symptoms were more common, and MoCA total scores were lower in the patient group. Fatigue, depressive symptoms, and higher anxiety levels were seen to have a negative effect on physical and mental health. Excessive daytime sleepiness had a negative effect on physical health. There is an emerging interest in nonmotor features of ET. This study showed that even young patients have nonmotor features that decrease their quality of life. This might tell us that nonmotor symptoms could be a part of the disease in the early stages.

  8. Estrogen-related receptor α is essential for the expression of antioxidant protection genes and mitochondrial function

    International Nuclear Information System (INIS)

    Rangwala, Shamina M.; Li, Xiaoyan; Lindsley, Loren; Wang, Xiaomei; Shaughnessy, Stacey; Daniels, Thomas G.; Szustakowski, Joseph; Nirmala, N.R.; Wu, Zhidan; Stevenson, Susan C.

    2007-01-01

    Estrogen-related receptor α (ERRα) is an important mediator of mitochondrial biogenesis and function. To investigate the transcriptional network controlling these phenomena, we investigated mitochondrial gene expression in embryonic fibroblasts isolated from ERRα null mice. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) stimulated mitochondrial gene expression program in control cells, but not in the ERRα null cells. Interestingly, the induction of levels of mitochondrial oxidative stress protection genes in response to increased PGC-1α levels was dependent on ERRα. Furthermore, we found that the PGC-1α-mediated induction of estrogen-related receptor γ and nuclear respiratory factor 2 (NRF-2), was dependent on the presence of ERRα. Basal levels of NRF-2 were decreased in the absence of ERRα. The absence of ERRα resulted in a decrease in citrate synthase enzyme activity in response to PGC-1α overexpression. Our results indicate an essential role for ERRα as a key regulator of oxidative metabolism

  9. The threonine protease activity of testes-specific protease 50 (TSP50 is essential for its function in cell proliferation.

    Directory of Open Access Journals (Sweden)

    Yu-Yin Li

    Full Text Available BACKGROUND: Testes-specific protease 50 (TSP50, a newly discovered threonine enzyme, has similar amino acid sequences and enzymatic structures to those of many serine proteases. It may be an oncogene. TSP50 is up-regulated in breast cancer epithelial cells, and ectopic expression of TSP50 in TSP50-deficient Chinese hamster ovary (CHO cells has been found to promote cell proliferation. However, the mechanisms by which TSP50 exerts its growth-promoting effects are not yet fully understood. METHODOLOGY/PRINCIPAL FINDINGS: To delineate whether the threonine protease activity of TSP50 is essential to its function in cell proliferation, we constructed and characterized a mutant TSP50, called TSP50 T310A, which was identified as a protease-dead mutant of TSP50. By a series of proliferation analyses, colony formation assays and apoptosis analyses, we showed that T310A mutation significantly depresses TSP50-induced cell proliferation in vitro. Next, the CHO stable cell line expressing either wild-type or T310A mutant TSP50 was injected subcutaneously into nude mice. We found that the T310A mutation could abolish the tumorigenicity of TSP50 in vivo. A mechanism investigation revealed that the T310A mutation prevented interaction between TSP50 and the NF-κBIκBα complex, which is necessary for TSP50 to perform its function in cell proliferation. CONCLUSION: Our data highlight the importance of threonine 310, the most critical protease catalytic site in TSP50, to TSP50-induced cell proliferation and tumor formation.

  10. Influence of soybean and corn gluten proteins as substitutes for milk protein in milk replacers on growth, liver and thyroid functions in buffalo calves

    International Nuclear Information System (INIS)

    Abdelaal, A.E.; EL-Ashry, M.A.; Ibrahim, I.I.; Fekry, A.E.; Elwan, K.M.

    1991-01-01

    Twenty suckling buffalo calves (3 weeks old) were allotted to four nutritional groups: Control group, fed 100% skim milk based replacer (Group a); and in the other three groups 50% of milk protein was substituted by american soybean flour (Group B) Egyptian soybean meal (Group C) and corn gluten (Group D). Fat was added to all replacers at the rate of 20% on dry basis. Calf starter and hay were offered ad libitum with the liquid diets from the fourth week. Body weight was recorded weekly. Serum proteins, cholesterol, T 4, T 3, and the enzymic activities of GOT, GPT and alkaline phosphatase were determined at 6, 9 and 12 weeks of age. The use of american soybean and corn gluten proteins resulted, approximately, in the same body weight gain as in skim milk fed group (A), indicating that whole milk can be reserved from human consumption and the calves can be reared on milk replacers containing plant proteins. Substitution of milk protein with soybean and corn gluten protein resulted in a significant increase in each of serum globulins, A/G ratio and cholesterol, significant decrease in serum total proteins and GPT activity, and no change in growth rate and thyroid function

  11. Functional outcome and health related quality of life after dual mobility cup total hip replacement for displaced femoral neck fractures in middle aged Egyptian patients.

    Science.gov (United States)

    Rashed, Ramy Ahmed; Sevenoaks, Hannah; Shabaan, Amira Mohammed; Choudry, Qaisar Akhlaq; Hammad, Abdullah Said; Kasem, Mohammed Samir; El Khadrawe, Tarek Aly; El Dakhakhny, Magdy Mohammed

    2018-03-01

    This study was done to assess the functional and clinical results after one year of cemented THR with dual mobility cup for the treatment of fracture neck femur in active middle-aged patients in Egypt (Middle Eastern population). This study included 31 patients (32 hips) with displaced femoral neck fractures that were admitted to El Hadara University Hospital, Alexandria, Egypt. Their mean age was 66.4 ± 5.9 years. Fifteen patients were females. All the patients were treated with total hip replacement using a cemented dual mobility cup (Ecofit ® 2 M, Implantcast GmbH, Germany) total hip replacement through the standard posterior approach. Functional assessment was done using Harris Hip Score (HHS), SF-36 questionnaire for health related quality of life (HRQoL) with assistance of a physiotherapist. The mean HHS improved over the follow up period from 79.04 ± 7.9 at 12 weeks to an average of 92.8 ± 11.1 at 1 year follow up. HRQoL measures showed a pattern of initial drop at 3 months postoperatively, then a steady rise to be restored at 1 year as compared to the preoperative baseline measures. There were no dislocations encountered in this series over one year follow up. The following complications were encountered; 1 deep infection, 2 deep vein thrombosis, 2 heterotopic ossifications, and 1 patient died within one year after surgery. Dual mobility cup total hip replacement is an acceptable method for treatment of displaced femoral neck fracture in active middle aged patients in Egypt as it provides pain relief and good function without compromising the stability. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  12. [The effect of pulmonary static inflation with sevoflurane during cardiopulmonary bypass on lung function in patients undergoing cardiac valve replacement surgery].

    Science.gov (United States)

    Shangguan, Wang-ning; Xiang, Yong; Liu, Jin

    2008-09-01

    To assess the phenomenon of lung injury after cardiopulmonary bypass (CPB) and the effects of pulmonary static inflation with sevoflurane during CPB on lung function in patients undergoing cardiac valve replacement surgery. Sixty adult patients (ASA II or III, aged 20-59 years) were randomly assigned to two groups, control group (n=30): pulmonary static inflation during CPB, no sevoflurane inhaled, sevoflurane group (n=30): pulmonary static inflation with 1.0 MAC sevoflurane during CPB. The pressure of pulmonary static inflation was maintained at 5 cm H2O in both groups. Arterial blood gas analysis was performed at time of operation starting (To)0 1, 3, 6 h after CPB (T1, TZ,2T3). The values of alveolar-arterial oxygen pressure difference ED[A-a)O2)2]respiratory index [RI, D(A-a)O2/2aO2)2and oxygenation index (OI, PaOz/2iOz)2were calculated respectively. Compared with control group, D(A-a)Oz,2RI and OI were not different in sevoflurane group at any stage; Compared with the baseline (To) in both groups, D (A-a)O2 2nd RI increased after CPB, and OI decreased (P impact of pulmonary function usually occur after cardiopulmonary bypass (CPB)in patients undergoing cardiac valve replacement surgery, of which peak injury within 6 h presents at 3 h after CPB. Static pulmonary inflation with 1.0 MAC sevoflurane during CPB shows no beneficial effects on lung function in patients undergoing cardiac valve replacement surgery.

  13. First pass radionuclide studies in evaluation of left and right ventricular function in patients with bioprosthetic mitral valve replacement after 9-11 years

    International Nuclear Information System (INIS)

    Reichart, B.; Schad, N.; Hatz, R.; Bougioukas, G.; Gallucci, V.; Bortolotti, U.; Milano, A.

    1985-01-01

    The results presented here show that first pass scintigraphy is an effective diagnostic tool in evaluating tissue valves at long term risk. At 123.8 +-8 months postoperatively, 13 out of 15 patients with porcine valves in the mitral position showed normal PTT, RFR and clinical function. Two patients with bioprostheses proven to be stenotic had abnormal PTT and RFR. Valve replacement was required in these patients. In 14 patients, left and right ESV and EDV were normal at rest. Left and right ventricular responses to exercise were abnormal since ESV and EDV did not change, possibly due to decreased ventricular compliance

  14. Chemical Composition of Essential Oils from Thymus vulgaris, Cymbopogon citratus, and Rosmarinus officinalis, and Their Effects on the HIV-1 Tat Protein Function.

    Science.gov (United States)

    Feriotto, Giordana; Marchetti, Nicola; Costa, Valentina; Beninati, Simone; Tagliati, Federico; Mischiati, Carlo

    2018-02-01

    New drugs would be beneficial to fight resistant HIV strains, in particular those capable of interfering with essential viral functions other than those targeted by highly active antiretroviral therapy drugs. Despite the central role played by Tat protein in HIV transcription, a search for vegetable extracts able to hamper this important viral function was never carried out. In this work, we evaluated the chemical composition and possible interference of essential oil from Thymus vulgaris, Cananga odorata, Cymbopogon citratus, and Rosmarinus officinalis with the Tat/TAR-RNA interaction and with Tat-induced HIV-1 LTR transcription. GC/MS Analysis demonstrated the biodiversity of herbal species translated into essential oils composed of different blends of terpenes. In all of them, 4 - 6 constituents represent from 81.63% to 95.19% of the total terpenes. Essential oils of Thymus vulgaris, Cymbopogon citratus, and Rosmarinus officinalis were active in interfering with Tat functions, encouraging further studies to identify single terpenes responsible for the antiviral activity. In view of the quite different composition of these essential oils, we concluded that their interference on Tat function depends on specific terpene or a characteristic blend. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

  15. Structural Features Reminiscent of ATP-Driven Protein Translocases Are Essential for the Function of a Type III Secretion-Associated ATPase.

    Science.gov (United States)

    Kato, Junya; Lefebre, Matthew; Galán, Jorge E

    2015-09-01

    Many bacterial pathogens and symbionts utilize type III secretion systems to interact with their hosts. These machines have evolved to deliver bacterial effector proteins into eukaryotic target cells to modulate a variety of cellular functions. One of the most conserved components of these systems is an ATPase, which plays an essential role in the recognition and unfolding of proteins destined for secretion by the type III pathway. Here we show that structural features reminiscent of other ATP-driven protein translocases are essential for the function of InvC, the ATPase associated with a Salmonella enterica serovar Typhimurium type III secretion system. Mutational and functional analyses showed that a two-helix-finger motif and a conserved loop located at the entrance of and within the predicted pore formed by the hexameric ATPase are essential for InvC function. These findings provide mechanistic insight into the function of this highly conserved component of type III secretion machines. Type III secretion machines are essential for the virulence or symbiotic relationships of many bacteria. These machines have evolved to deliver bacterial effector proteins into host cells to modulate cellular functions, thus facilitating bacterial colonization and replication. An essential component of these machines is a highly conserved ATPase, which is necessary for the recognition and secretion of proteins destined to be delivered by the type III secretion pathway. Using modeling and structure and function analyses, we have identified structural features of one of these ATPases from Salmonella enterica serovar Typhimurium that help to explain important aspects of its function. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Effects of the essential oil from fruits of Schinus terebinthifolius Raddi (Anacardiaceae) on reproductive functions in male rats

    OpenAIRE

    Affonso,Cristiano R. G.; Fernandes,Rozeverter M.; Oliveira,Jamylla M. G. de; Martins,Maria do Carmo de Carvalho e; Lima,Sidney G. de; Sousa Júnior,Gustavo R. de; Fernandes,Maria Zenaide de Lima C. Moreno; Zanini,Surama F.

    2012-01-01

    The essential oil of Schinus terebinthifolius (Anacardiaceae) was analyzed by GC and GC-MS. α-Fenchene, limonene, β-pinene, α-phellandrene, and β-isosylvestrene represent about 80% of the oil composition. The reproductive toxicity of the essential oil in Wistar male rats was evaluated. No changes were observed in the mass of the reproductive organs, number and morphology of spermatozoa, reproductive rates, and the body mass of offspring of male rats after treatment with the essential oil of S...

  17. Use of an Artificial Ligament Decreases Hip Dislocation and Improves Limb Function After Total Femoral Prosthetic Replacement Following Femoral Tumor Resection.

    Science.gov (United States)

    Du, Zhiye; Tang, Shun; Yang, Rongli; Tang, Xiaodong; Ji, Tao; Guo, Wei

    2017-12-27

    Hip dislocation is a major complication of total femoral prosthetic reconstruction (TFR) after femoral tumor resection. Hip dislocation can occur because of inadequate functional abductor musculature, inadequate hip capsule repair, or a long lever arm after total femur replacement. To eliminate the negative effects of these factors on the risk of hip dislocation, the use of artificial ligaments may help to increase the stability of the hip joint. We aimed to determine whether application of an artificial ligament would improve limb function and active range of movement (ROM) after TFR. Fifty-eight patients who underwent femoral tumor resection and TFR were included. A band-shaped artificial ligament was wrapped spirally around the proximal site of the total femur prosthesis for periacetabular soft tissue reconstruction in 12 patients. The other 46 patients did not consent to receiving the artificial ligament. Complications including hip dislocation and infection, limb function, and active hip ROM were compared between patients who did and did not receive the artificial ligament. The hip dislocation rate was lower in the patients who received the artificial ligament. The risk of deep infection did not differ between groups. The group that received the ligament also achieved better limb function and active ROM on flexion and abduction. Patients treated with total femur resection and endoprosthetic replacement with an artificial ligament for periacetabular soft tissue reconstruction had a more stable hip joint, better limb function, and greater active hip ROM than did patients who did not receive an artificial ligament. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Essential thrombocythemia

    Science.gov (United States)

    Primary thrombocythemia; Essential thrombocytosis ... the gums Prolonged bleeding from surgical procedures or tooth removal ... 68. Tefferi A. Polycythemia vera, essential thrombocythemia, and primary myelofibrosis. In: Goldman L, Schafer AI, eds. Goldman- ...

  19. Effect of early supervised progressive resistance training compared to unsupervised home-based exercise after fast-track total hip replacement applied to patients with preoperative functional limitations

    DEFF Research Database (Denmark)

    Mikkelsen, L R; Mechlenburg, I; Søballe, K

    2014-01-01

    OBJECTIVE: To examine if 2 weekly sessions of supervised progressive resistance training (PRT) in combination with 5 weekly sessions of unsupervised home-based exercise is more effective than 7 weekly sessions of unsupervised home-based exercise in improving leg-extension power of the operated leg...... 10 weeks after total hip replacement (THR) in patients with lower pre-operative function. METHOD: A total of 73 patients scheduled for THR were randomised (1:1) to intervention group (IG, home based exercise 5 days/week and PRT 2 days/week) or control group (CG, home based exercise 7 days...... of the operated leg, at the primary endpoint 10 weeks after surgery in THR patients with lower pre-operative function. TRIAL REGISTRATION: NCT01214954....

  20. Evaluation of left ventricular function in the patients with aortic regurgitation following aortic valve replacement by radionuclide cardiography

    International Nuclear Information System (INIS)

    Matsuzaki, Tomoya; Kazui, Teruhisa; Morikawa, Masayuki

    1989-01-01

    Twenty patients undergoing AVR were subjected to this study and divided into the early and the late groups. 6 healthy adults were dealt as the control group. The EF, PER, 1/3 EF, TPE were compared among these three groups both at rest and during exercise. The detailed responses to the exercise were measured by %Δ between at rest and during exercise. Furthermore, the LV function in the filling period were examined by the 1/3 FF and RFR at rest. This study suggests that although the left ventricular function and contractile reserve to the exercise remained insufficient in the early postoperative phase, nearly complete recovery of the reserve could be obtained in the late phase, while the left ventricular function in the rapid filling period was significantly decreased in both early and late postoperative phase. (author)

  1. Application of model of incremental haemodialysis, based on residual renal function, at the initiation of renal replacement therapy

    Directory of Open Access Journals (Sweden)

    José L. Merino

    2017-01-01

    Conclusions: Incremental HD treatment, with twice-weekly HD, may be an alternative in selected patients. This approach can largely preserve residual renal function at least for the first year. Although this pattern probably is not applicable to all patients starting RRT, it can and should be an initial alternative to consider.

  2. Home automation becomes home entertainment. Emotion replaces function; Hausautomation sucht Naehe zum Home-Entertainment. Emotion verdraengt Funktion

    Energy Technology Data Exchange (ETDEWEB)

    Schmid, W.

    2006-09-15

    Home automation commonly applies to control of lighting, shading, heating, safety etc., i.e. a purely functional concept. Recently, many systems have come to integrate home entertainment as well: Bang and Olufsen and Revox meets heating, light, and ventilation. (orig.)

  3. Early post-operative pulmonary function tests after mitral valve replacement: Minimally invasive versus conventional approach. Which is better?

    Directory of Open Access Journals (Sweden)

    Magdy Gomaa

    2016-12-01

    Conclusion: Minimally invasive right anterolateral mini-thoracotomy is as safe as median sternotomy for mitral valve surgery, with fewer complications and postoperative pain, less ICU and hospital stay, fast recovery to work with no movement restriction after surgery. There was a highly significant difference denoting better post operative pulmonary function of the minimally invasive approach.

  4. Alterations in the molecular species of rat liver lecithin by corn-oil feeding to essential fatty acid-deficient rats as a function of time

    NARCIS (Netherlands)

    Golde, L.M.G. van; Pieterson, W.A.; Deenen, L.L.M. van

    1968-01-01

    The present paper describes, as a function of time, the qualitative and quantitative alterations in the molecular species pattern of rat liver lecithin which are observed when corn oil is fed to essential fatty acid-deficient rats. One of the most important changes observed was a very rapid

  5. Human gene essentiality.

    Science.gov (United States)

    Bartha, István; di Iulio, Julia; Venter, J Craig; Telenti, Amalio

    2018-01-01

    A gene can be defined as essential when loss of its function compromises viability of the individual (for example, embryonic lethality) or results in profound loss of fitness. At the population level, identification of essential genes is accomplished by observing intolerance to loss-of-function variants. Several computational methods are available to score gene essentiality, and recent progress has been made in defining essentiality in the non-coding genome. Haploinsufficiency is emerging as a critical aspect of gene essentiality: approximately 3,000 human genes cannot tolerate loss of one of the two alleles. Genes identified as essential in human cell lines or knockout mice may be distinct from those in living humans. Reconciling these discrepancies in how we evaluate gene essentiality has applications in clinical genetics and may offer insights for drug development.

  6. Women with knee osteoarthritis have more pain and poorer function than men, but similar physical activity prior to total knee replacement

    Directory of Open Access Journals (Sweden)

    Tonelli Shalome M

    2011-11-01

    duration, pain catastrophizing, body mass index (BMI, and heat pain threshold; and (3 physical activity (average metabolic equivalent tasks (METS/day were BMI, age, Short-Form 36 (SF-36 Physical Function, Kellgren-Lawrence osteoarthritis grade, depression, and Knee Injury and Osteoarthritis Outcome Score (KOOS pain subscale. Conclusions Women continue to be as physically active as men prior to total knee replacement even though they have significantly more pain, greater pain sensitivity, poorer perceived function, and more impairment on specific functional tasks.

  7. Functional replacement of Wheat streak mosaic virus HC-Pro with the corresponding cistron from a diverse array of viruses in the family Potyviridae

    International Nuclear Information System (INIS)

    Stenger, Drake C.; French, Roy

    2004-01-01

    Helper component-proteinase (HC-Pro) of Wheat streak mosaic virus strain Sidney 81 (WSMV-Sidney 81) was systematically replaced with the corresponding cistron derived from four strains of WSMV (Type, TK1, CZ, and El Batan 3), the tritimovirus Oat necrotic mottle virus (ONMV), the rymoviruses Agropyron mosaic virus (AgMV) and Hordeum mosaic virus (HoMV), or the potyviruses Tobacco etch virus (TEV) and Turnip mosaic virus (TuMV). These HC-Pro proteins varied in amino acid sequence identity shared with HC-Pro of WSMV-Sidney 81 from high (strains of WSMV at ∼86-99%) to moderate (ONMV at 70%) to low (rymoviruses and potyviruses at ∼15-17%). Surprisingly, all chimeric viral genomes examined were capable of systemic infection of wheat upon inoculation with RNA transcripts produced in vitro. HC-Pro replacements derived from tritimoviruses did not alter host range relative to WSMV-Sidney 81, as each of these chimeric viruses was able to systemically infect wheat, oat, and corn line SDp2. These results indicate that differences in host range among tritimoviruses, including the inability of ONMV to infect wheat or the inability of WSMV strains Type and El Batan 3 to infect SDp2 corn, are not determined by HC-Pro. In contrast, all chimeric viruses bearing HC-Pro replacements derived from rymoviruses or potyviruses were unable to infect SDp2 corn and oat. Collectively, these results indicate that HC-Pro from distantly related virus species of the family Potyviridae are competent to provide WSMV-Sidney 81 with all functions necessary for infection of a permissive host (wheat) and that virus-host interactions required for systemic infection of oat and SDp2 corn are more stringent. Changes in symptom severity or mechanical transmission efficiency observed for some chimeric viruses further suggest that HC-Pro affects virulence in WSMV

  8. Exploring the relationships between International Classification of Functioning, Disability and Health (ICF) constructs of Impairment, Activity Limitation and Participation Restriction in people with osteoarthritis prior to joint replacement.

    Science.gov (United States)

    Pollard, Beth; Johnston, Marie; Dieppe, Paul

    2011-05-16

    The International Classification of Functioning, Disability and Health (ICF) proposes three main constructs, impairment (I), activity limitation (A) and participation restriction (P). The ICF model allows for all paths between the constructs to be explored, with significant paths likely to vary for different conditions. The relationships between I, A and P have been explored in some conditions but not previously in people with osteoarthritis prior to joint replacement. The aim of this paper is to examine these relationships using separate measures of each construct and structural equation modelling. A geographical cohort of 413 patients with osteoarthritis about to undergo hip and knee joint replacement completed the Aberdeen measures of Impairment, Activity Limitation and Participation Restriction (Ab-IAP). Confirmatory factor analysis was used to test the three factor (I, A, P) measurement model. Structural equation modelling was used to explore the I, A and P pathways in the ICF model. There was support from confirmatory factor analysis for the three factor I, A, P measurement model. The structural equation model had good fit [S-B Chi-square = 439.45, df = 149, CFI robust = 0.91, RMSEA robust = 0.07] and indicated significant pathways between I and A (standardised coefficient = 0.76 p < 0.0001) and between A and P (standardised coefficient = 0.75 p < 0.0001). However, the path between I and P was not significant (standardised coefficient = 0.01). The significant pathways suggest that treatments and interventions aimed at reducing impairment, such as joint replacement, may only affect P indirectly, through A, however, longitudinal data would be needed to establish this.

  9. A comparison of discharge functional status after rehabilitation in skilled nursing, home health, and medical rehabilitation settings for patients after lower-extremity joint replacement surgery.

    Science.gov (United States)

    Mallinson, Trudy R; Bateman, Jillian; Tseng, Hsiang-Yi; Manheim, Larry; Almagor, Orit; Deutsch, Anne; Heinemann, Allen W

    2011-05-01

    To examine differences in outcomes of patients after lower-extremity joint replacement across 3 post-acute care (PAC) rehabilitation settings. Prospective observational cohort study. Skilled nursing facilities (SNFs; n=5), inpatient rehabilitation facilities (IRFs; n=4), and home health agencies (HHAs; n=6) from 11 states. Patients with total knee (n=146) or total hip replacement (n=84) not related to traumatic injury. None. Self-care and mobility status at PAC discharge measured by using the Inpatient Rehabilitation Facility Patient Assessment Instrument. Based on our study sample, HHA patients were significantly less dependent than SNF and IRF patients at admission and discharge in self-care and mobility. IRF and SNF patients had similar mobility levels at admission and discharge and similar self-care at admission, but SNF patients were more independent in self-care at discharge. After controlling for differences in patient severity and length of stay in multivariate analyses, HHA setting was not a significant predictor of self-care discharge status, suggesting that HHA patients were less medically complex than SNF and IRF patients. IRF patients were more dependent in discharge self-care even after controlling for severity. For the full discharge mobility regression model, urinary incontinence was the only significant covariate. For the patients in our U.S.-based study, direct discharge to home with home care was the optimal strategy for patients after total joint replacement surgery who were healthy and had social support. For sicker patients, availability of 24-hour medical and nursing care may be needed, but intensive therapy services did not seem to provide additional improvement in functional recovery in these patients. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  10. Functional outcome, revision rates and mortality after primary total hip replacement--a national comparison of nine prosthesis brands in England.

    Science.gov (United States)

    Pennington, Mark; Grieve, Richard; Black, Nick; van der Meulen, Jan H

    2013-01-01

    The number of prosthesis brands used for hip replacement has increased rapidly, but there is little evidence on their effectiveness. We compared patient-reported outcomes, revision rates, and mortality for the three most frequently used brands within each prosthesis type: cemented (Exeter V40 Contemporary, Exeter V40 Duration and Exeter V40 Elite Plus Ogee), cementless (Corail Pinnacle, Accolade Trident, and Taperloc Exceed), and hybrid (Exeter V40 Trilogy, Exeter V40 Trilogy, and CPT Trilogy). We used three national databases of patients who had hip replacements between 2008 and 2011 in the English NHS to compare functional outcome (Oxford Hip Score (OHS) ranging from 0 (worst) to 48 (best)) in 43,524 patients at six months. We analysed revisions and mortality in 187,201 patients. We used multiple regression to adjust for pre-operative differences. Prosthesis type had an impact on post-operative OHS and revision rates (both pprosthesis type were small and not significant (p = 0.06). Functional outcome varied according to brand among cemented (p = 0.05, with Exeter V40 Duration having the best) and cementless prostheses (p = 0.01, with Corail Pinnacle having the best). Revision rates varied according to brand among hybrids (p = 0.05, with Exeter V40 Trident having the lowest). Functional outcomes were better with cementless cups and revision rates were lower with cemented stems, which underlies the good overall performance of hybrids. The hybrid Exeter V40 Trident seemed to produce the best overall results. This brand should be considered as a benchmark in randomised trials.

  11. Shoulder replacement - discharge

    Science.gov (United States)

    Total shoulder arthroplasty - discharge; Endoprosthetic shoulder replacement - discharge; Partial shoulder replacement - discharge; Partial shoulder arthroplasty - discharge; Replacement - shoulder - discharge; Arthroplasty - shoulder - discharge

  12. Effects of dexmedetomidine on H-FABP, CK-MB, cTnI levels, neurological function and near-term prognosis in patients undergoing heart valve replacement.

    Science.gov (United States)

    Wang, Zhi; Chen, Qiang; Guo, Hao; Li, Zhishan; Zhang, Jinfeng; Lv, Lei; Guo, Yongqing

    2017-12-01

    This study investigated the effects of dexmedetomidine on heart-type fatty acid binding protein (H-FABP), creatine kinase isoenzymes (CK-MB), and troponin I (cTnI) levels, neurological function and near-term prognosis in patients undergoing heart valve replacement. Patients undergoing heart valve replacement were randomly allocated to remifentanil anesthesia (control group, n=48) or dexmedetomidine anesthesia (observation group, n=48). Hemodynamic parameters were measured before anesthesia induction (T1), 1 min after intubation (T2), 10 min after start of surgery (T3), and on completion of surgery (T4). Levels of plasma H-FABP, CK-MB and cTnI were measured 10 min before anesthesia induction (C1), 10 min after start of surgery (C2), on completion of surgery (C3), 6 h after surgery (C4), and 24 h after surgery (C5). S100β protein and serum neuron-specific enolase (NSE) were detected 10 min before anesthesia induction (C1), and 24 h after surgery (C5). Neurological and cardiac function was evaluated 24 h after surgery. Incidence of cardiovascular adverse events was recorded for 1 year of follow-up. There were no significant differences in the average heart rate between the two groups during the perioperative period. The mean arterial pressure in the observation group was significantly lower than control group (PH-FABP, CK-MB and cTnI at C2, C3, C4 and C5, were significantly higher than C1, but significantly lower in the observation versus control group (P<0.05). Twenty-four hours after surgery, levels of S100β and NSE in both groups were higher than those before induction (P<0.05), but significantly lower in the observation versus control group (P<0.05). Twenty-four hours after surgery, neurological function scores were better, and myocardial contractility and arrhythmia scores significantly lower in the observation versus control group (P<0.05 for all). After follow-up for 1 year, incidence of cardiovascular adverse events was significantly lower in the observation

  13. Grasshopper Lazarillo, a GPI-anchored Lipocalin, increases Drosophila longevity and stress resistance, and functionally replaces its secreted homolog NLaz.

    Science.gov (United States)

    Ruiz, Mario; Wicker-Thomas, Claude; Sanchez, Diego; Ganfornina, Maria D

    2012-10-01

    Lazarillo (Laz) is a glycosyl-phosphatidylinositol (GPI)-linked glycoprotein first characterized in the developing nervous system of the grasshopper Schistocerca americana. It belongs to the Lipocalins, a functionally diverse family of mostly secreted proteins. In this work we test whether the protective capacity known for Laz homologs in flies and vertebrates (NLaz, GLaz and ApoD) is evolutionarily conserved in grasshopper Laz, and can be exerted from the plasma membrane in a cell-autonomous manner. First we demonstrate that extracellular forms of Laz have autocrine and paracrine protecting effects for oxidative stress-challenged Drosophila S2 cells. Then we assay the effects of overexpressing GPI-linked Laz in adult Drosophila and whether it rescues both known and novel phenotypes of NLaz null mutants. Local effects of GPI-linked Laz inside and outside the nervous system promote survival upon different stress forms, and extend lifespan and healthspan of the flies in a cell-type dependent manner. Outside the nervous system, expression in fat body cells but not in hemocytes results in protection. Within the nervous system, glial cell expression is more effective than neuronal expression. Laz actions are sexually dimorphic in some expression domains. Fat storage promotion and not modifications in hydrocarbon profiles or quantities explain the starvation-desiccation resistance caused by Laz overexpression. This effect is exerted when Laz is expressed ubiquitously or in dopaminergic cells, but not in hemocytes. Grasshopper Laz functionally restores the loss of NLaz, rescuing stress-sensitivity as well as premature accumulation of aging-related damage, monitored by advanced glycation end products (AGEs). However Laz does not rescue NLaz courtship behavioral defects. Finally, the presence of two new Lipocalins with predicted GPI-anchors in mosquitoes shows that the functional advantages of GPI-linkage have been commonly exploited by Lipocalins in the arthropodan lineage

  14. The effect and mechanism of growth hormone replacement on cognitive function in rats with traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Hao Zhang

    Full Text Available OBJECTIVE: The effects of growth hormone on cognitive dysfunction were observed in a controlled cortical impact (CCI rat model and the underlying mechanism was explored. METHOD: Three-month-old male SD rats were randomly divided into sham (n = 10, control (n = 10, and CCI groups (n = 40 The parameters were set as follows: striking speed, 3.5 m/s; impact depth, 1.5 mm; and dwell time, 400 msec. Eight and ten weeks post-injury, the GH levels were measured the water maze test and novel object recognition test were performed. CCI rats were divided into normal and decreased GH groups, and further randomly divided into two sub-groups (rhGH treatment and saline vehicle groups. All rats were tested for SYN, BDNF, and TrkB mRNA in the prefrontal cortex and hippocampus by RT-PCR. RESULTS: CCI rats 8 weeks post-injury had cognitive dysfunction regardless of the GH level (P<0.05. rhGH treatment improved cognitive function in CCI rats. There was a positive correlation between the expression of prefrontal BDNF and SYN mRNA in CCI rats after rhGH therapy and the water maze test score (r = 0.773 and 0.534, respectively; P<0.05. Furthermore, the expression of BDNF, TrkB, and SYN mRNA in the hippocampus was negatively correlated with the water maze test score (r = 0.602, 0.773, 0.672, and 0.783, respectively; P<0.05. There was a difference in the expression of hippocampal and prefrontal BDNF, TrkB, and SYN mRNA (P<0.05. CONCLUSION: rhGH treatment had a positive effect on cognitive function, which was more evident in GH-deficient rats. The increased expression of hippocampal and prefrontal BDNF and TrkB mRNA is implicated in rhGH therapy to improve cognitive function. Changes in the expression of hippocampal SYN mRNA following rhGH therapy may also play a role in improving cognitive function.

  15. A systematic analysis of Tinman function reveals Eya and JAK-STAT signaling as essential regulators of muscle development

    DEFF Research Database (Denmark)

    Liu, Ya-Hsin; Jakobsen, Janus S; Valentin, Guillaume

    2009-01-01

    Nk-2 proteins are essential developmental regulators from flies to humans. In Drosophila, the family member tinman is the major regulator of cell fate within the dorsal mesoderm, including heart, visceral, and dorsal somatic muscle. To decipher Tinman's direct regulatory role, we performed a time...

  16. A functional EXXEK motif is essential for proton coupling and active glucosinolate transport by NPF2.11

    DEFF Research Database (Denmark)

    Jørgensen, Morten Egevang; Olsen, Carl Erik; Geiger, Dietmar

    2015-01-01

    K motif variant in a plant NPF transporter. Using liquid chromatography-mass spectrometry (LC-MS)-based uptake assays and two-electrode voltage clamp (TEVC) electrophysiology, we demonstrate an essential role for the E1X1X2E2K motif for accumulation of substrate by NPF2.11. Our data suggest...

  17. Content, composition, and bioactivity of the essential oils of three basil genotypes as a function of harvesting.

    Science.gov (United States)

    Zheljazkov, Valtcho D; Cantrell, Charles L; Tekwani, Babu; Khan, Shabana I

    2008-01-23

    A study was conducted to evaluate the effect of cut on biomass productivity, oil content, composition, and bioactivity of Ocimum basilicum L. (cvs. German and Mesten) and Ocimum sanctum L. (syn. O. tenuiflorum L.) (cv. Local) in Mississippi. Yields of basil herbage and essential oil were high and comparable to those reported in the literature. Essential oil content of O. basilicum cv. German varied from 0.40 to 0.75%, the oil content of cv. Mesten varied from 0.50 to 0.72%, and the oil content of cv. Local (of O. sanctum) ranged from 0.17 to 0.50% in air-dried basil. Herbage and essential oil yields of cvs. German and Mesten of O. basilicum increased with the second and then again with the third cut, whereas herbage and oil yields of cv. Local of O. sanctum increased with the third cut relative to the previous cuts. Overall, essential oil yields were 115, 123, and 51 kg/ha for the cvs. German, Mesten, and Local, respectively. The major oil constituents of cvs. German and Mesten (of O. basilicum) were (-)-linalool (30-40%) and eugenol (8-30%), whereas the major oil constituents of cv. Local (of O. sanctum) were eugenol (8-43%) and methylchavicol (15-27%). Essential oils from both species grown in Mississippi showed in vitro activity against Leishmania donovani (IC50 = 37.3-49.6 microg/mL), which was comparable to the activity of commercial oil (IC50 = 40-50 microg/mL). Minor basil oil constituents (+)-delta-cadinene, 3-carene, alpha-humulene, citral, and (-)- trans-caryophyllene had antileishmanial activity, whereas other constituents were ineffective. None of the oil was cytotoxic to mammalian cells.

  18. Replacing sedentary time with sleep, light, or moderate-to-vigorous physical activity: effects on self-regulation and executive functioning.

    Science.gov (United States)

    Fanning, J; Porter, G; Awick, E A; Ehlers, D K; Roberts, S A; Cooke, G; Burzynska, A Z; Voss, M W; Kramer, A F; McAuley, E

    2017-04-01

    Recent attention has highlighted the importance of reducing sedentary time for maintaining health and quality of life. However, it is unclear how changing sedentary behavior may influence executive functions and self-regulatory strategy use, which are vital for the long-term maintenance of a health behavior regimen. The purpose of this cross-sectional study is to examine the estimated self-regulatory and executive functioning effects of substituting 30 min of sedentary behavior with 30 min of light activity, moderate-to-vigorous physical activity (MVPA), or sleep in a sample of older adults. This study reports baseline data collected from low-active healthy older adults (N = 247, mean age 65.4 ± 4.6 years) recruited to participate in a 6 month randomized controlled exercise trial examining the effects of various modes of exercise on brain health and function. Each participant completed assessments of physical activity self-regulatory strategy use (i.e., self-monitoring, goal-setting, social support, reinforcement, time management, and relapse prevention) and executive functioning. Physical activity and sedentary behaviors were measured using accelerometers during waking hours for seven consecutive days at each time point. Isotemporal substitution analyses were conducted to examine the effect on self-regulation and executive functioning should an individual substitute sedentary time with light activity, MVPA, or sleep. The substitution of sedentary time with both sleep and MVPA influenced both self-regulatory strategy use and executive functioning. Sleep was associated with greater self-monitoring (B = .23, p = .02), goal-setting (B = .32, p replacing sedentary time with sleep and MVPA, individuals may bolster several important domains of self-regulatory behavior and executive functioning. This has important implications for the design of long-lasting health behavior interventions. Trial Registration clinicaltrials.gov identifier NCT00438347.

  19. Effect of immediate functional loading on osseointegration of implants used for single tooth replacement. A human histological study.

    Science.gov (United States)

    Donati, Mauro; Botticelli, Daniele; La Scala, Vincenzo; Tomasi, Cristiano; Berglundh, Tord

    2013-07-01

    To analyze hard tissue reactions to immediate functionally loaded single implants that were installed either with a conventional drill preparation procedure or with an osteotome preparation technique. Thirteen subjects with two sites requiring single tooth rehabilitation by means of implants volunteered for the study. Each subject received one test (immediate functionally loaded) and one control (non-loaded) implant. In six subjects (group 1) the implants were placed using a conventional drilling procedure, whereas in the remaining seven subjects (group 2) an osteotome preparation procedure was performed. Block biopsies containing test and control implants and peri-implant bone tissues were collected at 1 month in four of the subjects in group 1 and in five subjects of group 2. The remaining implant sites were sampled at 3 months after implant placement. The biopsies were prepared for histological examination. Two implants of the test-2 group (osteotome preparation) representing 1 month of healing and another test-2 implant representing 3 months of healing failed to integrate. A multilevel multivariate statistical analysis demonstrated that no differences in bone-to-implant contact (BIC)% were found in between test and control implants, the density of newly formed peri-implant bone was significantly higher around test than control implants at 1 and 3 months of healing. Sections representing osteotome technique sites showed fractured trabeculae and large amounts of bone particles. It is suggested that immediate loading of implants does not influence the osseointegration process, whereas the density of newly formed peri-implant bone at such sites appears to be increased in relation to unloaded control implants. The use of an osteotome preparation technique during installation results in damage of peri-implant bone and enhances the risk for failure in osseointegration. © 2012 John Wiley & Sons A/S.

  20. Hip joint replacement

    Science.gov (United States)

    Hip arthroplasty; Total hip replacement; Hip hemiarthroplasty; Arthritis - hip replacement; Osteoarthritis - hip replacement ... your activities. Most of the time, hip joint replacement is done in people age 60 and older. ...

  1. Controlled expression of nif and isc iron-sulfur protein maturation components reveals target specificity and limited functional replacement between the two systems.

    Science.gov (United States)

    Dos Santos, Patricia C; Johnson, Deborah C; Ragle, Brook E; Unciuleac, Mihaela-Carmen; Dean, Dennis R

    2007-04-01

    The nitrogen-fixing organism Azotobacter vinelandii contains at least two systems that catalyze formation of [Fe-S] clusters. One of these systems is encoded by nif genes, whose products supply [Fe-S] clusters required for maturation of nitrogenase. The other system is encoded by isc genes, whose products are required for maturation of [Fe-S] proteins that participate in general metabolic processes. The two systems are similar in that they include an enzyme for the mobilization of sulfur (NifS or IscS) and an assembly scaffold (NifU or IscU) upon which [Fe-S] clusters are formed. Normal cellular levels of the Nif system, which supplies [Fe-S] clusters for the maturation of nitrogenase, cannot also supply [Fe-S] clusters for the maturation of other cellular [Fe-S] proteins. Conversely, when produced at the normal physiological levels, the Isc system cannot supply [Fe-S] clusters for the maturation of nitrogenase. In the present work we found that such target specificity for IscU can be overcome by elevated production of NifU. We also found that NifU, when expressed at normal levels, is able to partially replace the function of IscU if cells are cultured under low-oxygen-availability conditions. In contrast to the situation with IscU, we could not establish conditions in which the function of IscS could be replaced by NifS. We also found that elevated expression of the Isc components, as a result of deletion of the regulatory iscR gene, improved the capacity for nitrogen-fixing growth of strains deficient in either NifU or NifS.

  2. Kidney function and 24-hour proteinuria in patients with Fabry disease during 36 months of agalsidase alfa enzyme replacement therapy: a Brazilian experience.

    Science.gov (United States)

    Thofehrn, Scheila; Netto, Cristina; Cecchin, Cláudia; Burin, Maira; Matte, Ursula; Brustolin, Sílvia; Nunes, Ane Cláudia Fernandes; Coelho, Janice; Tsao, Marylin; Jardim, Laura; Giugliani, Roberto; Barros, Elvino José Guardão

    2009-01-01

    Prior to the introduction of enzyme replacement therapy (ERT), management of Fabry disease (FD) consisted of symptomatic and palliative measures. ERT has been available for several years using recombinant human agalsidase alfa, an analogue of alpha-galactosidase A (GALA). However, the limitations of ERT in improving kidney function have not been established. This study evaluates the safety and therapeutic effect of agalsidase alfa replacement in terms of kidney function and reduction in 24-hour proteinuria. During the period between January 1, 2002, and August 1, 2005, nine Fabry patients (7 male, 2 female) were treated according to protocol, receiving 0.2 mg/kg agalsidase alfa IV every two weeks. Kidney function was evaluated by measuring the glomerular filtration rate (GFR) using chromium ethylene diamine tetra-acetate clearance ((51)Cr-EDTA mL/min/ 1.73 m(2)) at baseline, 12, 24, and 36 months. 24-hour proteinuria was measured at baseline, 3, 6, 12, 18, 24, and 36 months of ERT. Kidney disease was classified according to National Kidney Foundation Disease Outcome Quality Initiative (NKF/DOQI) Advisory Board criteria, which define stage I chronic kidney disease (CKD) as GFR >or= 90 mL/min/1.73 m(2), stage II as 60-89 mL/min/1.73 m(2), stage III as 30-59 mL/min/1.73 m(2), stage IV as 15-29 mL/min/1.73 m(2), and stage V as < 15 mL/min/1.73 m(2). Six patients completed 36 months of therapy, 2 patients completed 18 months, and 1 patient completed 12 months. Mean patient age at baseline was 34.6 +/- 11.3 years. During the study period, kidney function remained stable in patients with stages I, II, or III CKD. One patient, who entered the study with stage IV CKD, progressed to end-stage chronic kidney disease, beginning hemodialysis after 7 months and receiving a kidney transplant after 12 months of ERT. Proteinuria also remained stable in the group of patients with pathologic proteinuria. The use of agalsidase alfa was well tolerated in 99.5% of the infusions

  3. Effects of acute volume loading on kidney function in patients with essential hypertension, as estimated by the lithium clearance method

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; Svendsen, U G; Leyssac, P P

    1985-01-01

    This study investigated the mechanism underlying the exaggerated natriuresis seen in patients with essential hypertension. The study used the lithium clearance method, which permits accurate determination of both proximal and distal sodium reabsorption in man. One litre of isotonic sodium chlorid...... the normal response to sodium loading being reset to a lower level. This resetting may be a secondary consequence of the high blood pressure, since lowering the pressure abolishes the phenomenon....

  4. KNIME essentials

    CERN Document Server

    Bakos, Gábor

    2013-01-01

    KNIME Essentials is a practical guide aimed at getting the results you want, as quickly as possible.""Knime Essentials"" is written for data analysts looking to quickly get up to speed using the market leader in data processing tools, KNIME. No knowledge of KNIME is required, but we will assume that you have some background in data processing.

  5. Calculus III essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Calculus III includes vector analysis, real valued functions, partial differentiation, multiple integrations, vector fields, and infinite series.

  6. Calculus I essentials

    CERN Document Server

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Calculus I covers functions, limits, basic derivatives, and integrals.

  7. Pre-calculus essentials

    CERN Document Server

    Woodward, Ernest

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Pre-Calculus reviews sets, numbers, operations and properties, coordinate geometry, fundamental algebraic topics, solving equations and inequalities, functions, trigonometry, exponents

  8. Empirical D3 Dispersion as a Replacement for ab Initio Dispersion Terms in Density Functional Theory-Based Symmetry-Adapted Perturbation Theory.

    Science.gov (United States)

    Sedlak, Robert; Řezáč, Jan

    2017-04-11

    In density functional theory-based symmetry-adapted perturbation theory (DFT-SAPT) interaction energy calculations, the most demanding step is the calculation of the London dispersion term. For this bottleneck to be avoided and DFT-SAPT to be made applicable to larger systems, the ab initio dispersion terms can be replaced by one calculated empirically at an almost negligible cost ( J. Phys. Chem. A 2011 ; 115 , 11321 - 11330 ). We present an update of this approach that improves accuracy and makes the method applicable to a wider range of systems. It is based on Grimme's D3 dispersion correction for DFT, where the damping function is changed to one suitable for the calculation of the complete dispersion energy. The best results have been achieved with the Tang-Toennies damping function. It has been parametrized on the S66×8 data set for which we report density fitting DFT-SAPT/aug-cc-pVTZ interaction energy decomposition. The method has been validated on a diverse set of noncovalent systems including difficult cases such as very compact noncovalent complexes of charge-transfer type. The root-mean-square errors in the complete test set are 0.73 and 0.42 kcal mol -1 when charge-transfer complexes are excluded. The proposed empirical dispersion terms can also be used outside the DFT-SAPT framework, e.g., for the estimation of the amount of dispersion in a calculation where only the total interaction energy is known.

  9. Effects of 1-year growth hormone replacement therapy on thyroid volume and function of the children and adolescents with idiopathic growth hormone deficiency.

    Science.gov (United States)

    Keskin, Meliksah; Bayramoglu, Elvan; Aycan, Zehra

    2017-10-26

    There are different opinions about the effects of growth hormone replacement therapy (GHRT) on thyroid function and volume. This study aimed to assess the effects of GHRT on thyroid volume and function in the children and adolescents with growth hormone (GH) deficiency. A total of 29 patients diagnosed with GH deficiency were enrolled in the study. The control group consisted of 29 cases matched for age, gender and pubertal period with the patients. Thyroid function tests and insulin-like growth factor levels were measured, simultaneously thyroid volumes were assessed by ultrasonography at the initiation period and at the end of GHRT. Thyroid volumes of the patient group was -0.55±1.1 standard deviations (SDs) initially; whereas at the end of 1 year it was found to be -0.29±1.29 SDs and both SDs of thyroid volumes did not differ significantly. The SDs of thyroid volume of the control group was -0.85±1.03 SDs initially and -0.72±0.85 SDs at the end of 1 year; and they did not differ significantly. On the other hand, after GHRT of 1 year, thyroid stimulating hormone (TSH) and free thyroxine (T4) levels decreased. It was observed that SDs of thyroid gland volumes did not change in GH deficient children and adolescents after GHRT.

  10. Lipid Replacement Therapy: a Functional Food Approach with New Formulations for Reducing Cellular Oxidative Damage, Cancer-Associated Fatigue and the Adverse Effects of Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Garth L. Nicolson

    2011-04-01

    Full Text Available Backgroud:Cancer-associated fatigue and the chronic adverse effects of cancer therapy can be reduced by Lipid Replacement Therapy (LRT using membrane phospholipid mixtures given as food supplements.Methods:This is a review of the published literature on LRT and its uses.Results: LRT significantly reduced fatigue in cancer patients as well as patients suffering from chronic fatiguing illnesses and other medical conditions. It also reduced the adverse effects of chemotherapy, resulting in improvements in incidence of fatigue, nausea, diarrhea, impaired taste, constipation, insomnia and other quality of life indicators. In other diseases, such as chronic fatigue syndrome, fibromyalgia syndrome and other chronic fatiguing illnesses, LRT reduced fatigue by 35.5-43.1% in different clinical trials and increased mitochondrial function.Conclusions: LRT formulations appear to be useful as non-toxic dietary supplements for direct use or placed in functional foods to reduce fatigue and restore mitochondrial and other cellular membrane functions. Formulations of LRT phospholipids are suitable for addition to variousfood products for the treatment of a variety of chronic illnesses as well as their application inanti-aging and other health supplements and products.

  11. Complex variables I essentials

    CERN Document Server

    Solomon, Alan D

    2013-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Complex Variables I includes functions of a complex variable, elementary complex functions, integrals of complex functions in the complex plane, sequences and series, and poles and r

  12. Complex variables II essentials

    CERN Document Server

    Solomon, Alan D

    2013-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Complex Variables II includes elementary mappings and Mobius transformation, mappings by general functions, conformal mappings and harmonic functions, applying complex functions to a

  13. Functional outcome, revision rates and mortality after primary total hip replacement--a national comparison of nine prosthesis brands in England.

    Directory of Open Access Journals (Sweden)

    Mark Pennington

    Full Text Available The number of prosthesis brands used for hip replacement has increased rapidly, but there is little evidence on their effectiveness. We compared patient-reported outcomes, revision rates, and mortality for the three most frequently used brands within each prosthesis type: cemented (Exeter V40 Contemporary, Exeter V40 Duration and Exeter V40 Elite Plus Ogee, cementless (Corail Pinnacle, Accolade Trident, and Taperloc Exceed, and hybrid (Exeter V40 Trilogy, Exeter V40 Trilogy, and CPT Trilogy.We used three national databases of patients who had hip replacements between 2008 and 2011 in the English NHS to compare functional outcome (Oxford Hip Score (OHS ranging from 0 (worst to 48 (best in 43,524 patients at six months. We analysed revisions and mortality in 187,201 patients. We used multiple regression to adjust for pre-operative differences. Prosthesis type had an impact on post-operative OHS and revision rates (both p<0.001. Patients with hybrid prostheses had the best functional outcome (mean OHS 39.4, 95%CI 39.1 to 39.7 and those with cemented prostheses the worst (37.7, 37.3 to 38.1. Patients with cemented prostheses had the lowest reported 5-year revision rates (1.3%, 1.2% to 1.4% and those with cementless prostheses the highest (2.2%, 2.1% to 2.4%. Differences in mortality according to prosthesis type were small and not significant (p = 0.06. Functional outcome varied according to brand among cemented (p = 0.05, with Exeter V40 Duration having the best and cementless prostheses (p = 0.01, with Corail Pinnacle having the best. Revision rates varied according to brand among hybrids (p = 0.05, with Exeter V40 Trident having the lowest.Functional outcomes were better with cementless cups and revision rates were lower with cemented stems, which underlies the good overall performance of hybrids. The hybrid Exeter V40 Trident seemed to produce the best overall results. This brand should be considered as a benchmark in randomised trials.

  14. Prioritizing equipment for replacement.

    Science.gov (United States)

    Capuano, Mike

    2010-01-01

    It is suggested that clinical engineers take the lead in formulating evaluation processes to recommend equipment replacement. Their skill, knowledge, and experience, combined with access to equipment databases, make them a logical choice. Based on ideas from Fennigkoh's scheme, elements such as age, vendor support, accumulated maintenance cost, and function/risk were used.6 Other more subjective criteria such as cost benefits and efficacy of newer technology were not used. The element of downtime was also omitted due to the data element not being available. The resulting Periop Master Equipment List and its rationale was presented to the Perioperative Services Program Council. They deemed the criteria to be robust and provided overwhelming acceptance of the list. It was quickly put to use to estimate required capital funding, justify items already thought to need replacement, and identify high-priority ranked items for replacement. Incorporating prioritization criteria into an existing equipment database would be ideal. Some commercially available systems do have the basic elements of this. Maintaining replacement data can be labor-intensive regardless of the method used. There is usually little time to perform the tasks necessary for prioritizing equipment. However, where appropriate, a clinical engineering department might be able to conduct such an exercise as shown in the following case study.

  15. Astronomy essentials

    CERN Document Server

    Brass, Charles O

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Astronomy includes the historical perspective of astronomy, sky basics and the celestial coordinate systems, a model and the origin of the solar system, the sun, the planets, Kepler'

  16. Non-Hematopoietic Essential Functions of Bone Marrow Cells: A Review of Scientific and Clinical Literature and Rationale for Treating Bone Defects.

    Science.gov (United States)

    Harrell, David B; Caradonna, Eugenio; Mazzucco, Laura; Gudenus, Rosmarie; Amann, Berthold; Prochazka, Vaclav; Giannoudis, Peter V; Hendrich, Christian; Jäger, Marcus; Krauspe, Rüdiger; Hernigou, Philippe

    2015-12-28

    Hematopoiesis as the only essential function of bone marrow cells has been challenged for several decades through basic science (in vitro and in vivo) and clinical data. Such work has shed light on two other essential functions of bone marrow cells: osteopoiesis and angio-genesis/vasculogenesis. Clinical utility of autologous concentrated bone marrow aspirate (CBMA) has demonstrated both safety and efficacy in treating bone defects. Moreover, CBMA has been shown to be comparable to the gold standard of iliac crest bone graft (ICBG), or autograft, with regard to being osteogenic and osteoinductive. ICBG is not considered an advanced therapy medicinal product (ATMP), but CBMA may become regulated as an ATMP. The European Medicines Agency Committee for Advanced Therapies (EMA:CAT) has issued a reflection paper (20 June 2014) in which reversal of the 2013 ruling that CBMA is a non-ATMP has been proposed. We review bone marrow cell involvement in osteopoiesis and angiogenesis/vasculogenesis to examine EMA:CAT 2013 decision to use CBMA for treatment of osteonecrosis (e.g, of the femoral head) should be considered a non-ATMP. This paper is intended to provide discussion on the 20 June 2014 reflection paper by reviewing two non-hematopoietic essential functions of bone marrow cells. Additionally, we provide clinical and scientific rationale for treating osteonecrosis with CBMA.

  17. Non-hematopoietic essential functions of bone marrow cells: a review of scientific and clinical literature and rationale for treating bone defects

    Directory of Open Access Journals (Sweden)

    David B. Harrell

    2015-12-01

    Full Text Available Hematopoiesis as the only essential function of bone marrow cells has been challenged for several decades through basic science (in vitro and in vivo and clinical data. Such work has shed light on two other essential functions of bone marrow cells: osteopoiesis and angiogenesis/vasculogenesis. Clinical utility of autologous concentrated bone marrow aspirate (CBMA has demonstrated both safety and efficacy in treating bone defects. Moreover, CBMA has been shown to be comparable to the gold standard of iliac crest bone graft (ICBG, or autograft, with regard to being osteogenic and osteoinductive. ICBG is not considered an advanced therapy medicinal product (ATMP, but CBMA may become regulated as an ATMP. The European Medicines Agency Committee for Advanced Therapies (EMA:CAT has issued a reflection paper (20 June 2014 in which reversal of the 2013 ruling that CBMA is a non-ATMP has been proposed. We review bone marrow cell involvement in osteopoiesis and angiogenesis/vasculogenesis to examine EMA:CAT 2013 decision to use CBMA for treatment of osteonecrosis (e.g, of the femoral head should be considered a non-ATMP. This paper is intended to provide discussion on the 20 June 2014 reflection paper by reviewing two non-hematopoietic essential functions of bone marrow cells. Additionally, we provide clinical and scientific rationale for treating osteonecrosis with CBMA.

  18. The plant microtubule-associated protein AtMAP65-3/PLE is essential for cytokinetic phragmoplast function.

    Science.gov (United States)

    Müller, Sabine; Smertenko, Andrei; Wagner, Vera; Heinrich, Maria; Hussey, Patrick J; Hauser, Marie-Theres

    2004-03-09

    Directional cell expansion in interphase and nuclear and cell division in M-phase are mediated by four microtubule arrays, three of which are unique to plants: the interphase array, the preprophase band, and the phragmoplast. The plant microtubule-associated protein MAP65 has been identified as a key structural component in these arrays. The Arabidopsis genome has nine MAP65 genes, and here we show that one, AtMAP65-3/PLE, locates only to the mitotic arrays and is essential for cytokinesis. The Arabidopsis pleiade (ple) alleles are single recessive mutations, and we show that these mutations are in the AtMAP65-3 gene. Moreover, these mutations cause C-terminal truncations that abolish microtubule binding. In the ple mutants the anaphase spindle is normal, and the cytokinetic phragmoplast can form but is distorted; not only is it wider, but the midline, the region where oppositely oriented microtubules overlap, is unusually expanded. Here we present data that demonstrate an essential role for AtMAP65-3/PLE in cytokinesis in plant cells.

  19. The N-domain of Pex22p can functionally replace the Pex3p N-domain in targeting and peroxisome formation.

    Science.gov (United States)

    Halbach, André; Rucktäschel, Robert; Rottensteiner, Hanspeter; Erdmann, Ralf

    2009-02-06

    Pex3p is a central component of the import machinery for peroxisomal membrane proteins (PMPs) that can reach peroxisomes via the endoplasmic reticulum (ER) and even trigger de novo peroxisome formation from the ER. Pex19p is the import receptor for type I PMPs, whereas targeting of type II PMPs, of which Pex3p so far represents the only species, does not require Pex19p. Pex3p possesses two domains with distinct function: a short N-terminal domain, which harbors the information for peroxisomal (and ER) targeting, and a C-terminal domain, which faces the cytosol and serves as a docking site for Pex19p, thereby delivering newly synthesized PMPs to the peroxisome. Here we show that the N-terminal domain of Pex3p can be functionally replaced by the N-terminal peroxisomal membrane targeting signal (mPTS) of Pex22p, a supposedly unrelated component of the import machinery for peroxisomal matrix proteins. An exchange of the mPTS of Pex22p by that of Pex3p likewise fully preserved the function of Pex22p. Neither of the two mPTS interacted with Pex19p, and in the absence of Pex19p, colocalization of Pex3p and Pex22p was observed, indicating that also Pex22p is targeted to peroxisomes by a type II mPTS. When a type I mPTS was hooked to the C-terminal domains of Pex22p and Pex3p, function was retained in the case of Pex22p and in part even for Pex3p. The C-terminal domain of Pex3p thus contains the relevant information required for de novo peroxisome formation, thereby challenging the concept of the N terminus of Pex3p being key in that process.

  20. Effects of testosterone replacement therapy withdrawal and re-treatment in hypogonadal elderly men upon obesity, voiding function and prostate safety parameters.

    Science.gov (United States)

    Yassin, Aksam; Nettleship, Joanne E; Talib, Raidh A; Almehmadi, Yousef; Doros, Gheorge

    2016-01-01

    Whether testosterone replacement therapy (TRT) is a lifelong treatment for men with hypogonadism remains unknown. We investigated long-term TRT and TRT withdrawal on obesity and prostate-related parameters. Two hundred and sixty-two hypogonadal patients (mean age 59.5) received testosterone undecanoate in 12-week intervals for a maximum of 11 years. One hundred and forty-seven men had TRT interrupted for a mean of 16.9 months and resumed thereafter (Group A). The remaining 115 patients were treated continuously (Group B). Prostate volume, prostate-specific antigen (PSA), residual voiding volume, bladder wall thickness, C-reactive protein (CRP), aging male symptoms (AMS), International Index of erectile function - erectile function (IIEF-EF) and International Prostate Symptoms Scores (IPSS) were measured over the study period with anthropometric parameters of obesity, including weight, body mass index (BMI) and waist circumference. Prior to interruption, TRT resulted in improvements in residual voiding volume, bladder wall thickness, CRP, AMS, IIEF-EF, IPSS and obesity parameters while PSA and prostate volume increased. TRT interruption reduced total testosterone to hypogonadal levels in Group A and resulted in worsening of obesity parameters, AMS, IPSS, residual voiding volume and bladder wall thickness, IIEF-EF and PSA while CRP and prostate volume were unchanged until treatment resumed whereby these effects were reversed. TRT interruption results in worsening of symptoms. Hypogonadism may require lifelong TRT.

  1. Service water system repair/replacement guidelines: Planning and implementation

    International Nuclear Information System (INIS)

    Frederick, G.J.; Gandy, D.W.; Peterson, A.G. Jr.; Findlan, S.J.

    1993-11-01

    Service water system failures have prompted concerns related to extended power plant operating life and plant availability. Selection and procurement of materials for repair or replacement of piping and components may be the most important factors in improving service water system reliability. The authors examined factors that contribute to reduced SWS reliability. The factors include material selection inadequacies, water treatment problems, operational/maintenance practices, fabrication procedures, environmental degradation mechanisms, and coating problems. The authors investigated material selection for replacement and repair, taking into account fabrication practices, environmental concerns, and cost comparisons of materials. They examined specific components such as piping, pumps, valves, and heat exchangers with regard to material selection and fabrication practice. Although proper material selection is essential in upgrading and maintaining the designed functions of a SWS, it is critical to address SWS repair/replacement activities with a systemwide approach. Degradation of materials in SWS applications are plant specific, depending on factors unique to each site such as geographic location, existing materials, operating procedures, and environment. All these characteristics must be addressed in making repair/replacement decisions. Criteria that must be integrated for successful long-term operation of SWS include the following: Materials selection (upgrade or in-kind replacement), Evaluation of root cause or nature of the failure mechanism, Scope of the repair/replacement activities, Material compatibility of the existing materials, Operational and maintenance procedures, Code or jurisdictional requirements, Economic considerations, Water treatment programs, System design improvements or modifications

  2. An abstract machine for module replacement

    OpenAIRE

    Walton, Chris; Krl, Dilsun; Gilmore, Stephen

    1998-01-01

    In this paper we define an abstract machine model for the mλ typed intermediate language. This abstract machine is used to give a formal description of the operation of run-time module replacement from the programming language Dynamic ML. The essential technical device which we employ for module replacement is a modification of two-space copying garbage collection.

  3. A randomized clinical trial of a peri-operative behavioral intervention to improve physical activity adherence and functional outcomes following total knee replacement

    Directory of Open Access Journals (Sweden)

    Zheng Hua

    2011-10-01

    Full Text Available Abstract Background Total knee replacement (TKR is a common and effective surgical procedure to relieve advanced knee arthritis that persists despite comprehensive medical treatment. Although TKR has excellent technical outcomes, significant variation in patient-reported functional improvement post-TKR exists. Evidence suggests that consistent post-TKR exercise and physical activity is associated with functional gain, and that this relationship is influenced by emotional health. The increasing use of TKR in the aging US population makes it critical to find strategies that maximize functional outcomes. Methods/Design This randomized clinical trial (RCT will test the efficacy of a theory-based telephone-delivered Patient Self-Management Support intervention that seeks to enhance adherence to independent exercise and activity among post- TKR patients. The intervention consists of 12 sessions, which begin prior to surgery and continue for approximately 9 weeks post-TKR. The intervention condition will be compared to a usual care control condition using a randomized design and a probabilistic sample of men and women. Assessments are conducted at baseline, eight weeks, and six- and twelve- months. The project is being conducted at a large healthcare system in Massachusetts. The study was designed to provide greater than 80% power for detecting a difference of 4 points in physical function (SF36/Physical Component Score between conditions (standard deviation of 10 at six months with secondary outcomes collected at one year, assuming a loss to follow up rate of no more than 15%. Discussion As TKR use expands, it is important to develop methods to identify patients at risk for sub-optimal functional outcome and to effectively intervene with the goal of optimizing functional outcomes. If shown efficacious, this peri-TKR intervention has the potential to change the paradigm for successful post-TKR care. We hypothesize that Patient Self-Management Support

  4. Comment: Replacing Factionalism with Functionalism.

    Science.gov (United States)

    Carr, Edward G.

    1991-01-01

    The comment on a paper about the use of aversive interventions with developmentally disabled persons (EC 602 022) questions the effectiveness of aversive interventions and suggests effective nonaversive or less aversive interventions can usually be found. (DB)

  5. Pre-fabricated zirconium dioxide implant abutments for single-tooth replacement in the posterior region: success and failure after 3 years of function.

    Science.gov (United States)

    Nothdurft, Frank P; Nonhoff, Joerg; Pospiech, Peter R

    2014-07-01

    Zirconia implant abutments have gained a much broader clinical use over the past few years. The aim of the present study was to assess the clinical performance of a pre-fabricated zirconium dioxide implant abutment for single-tooth replacement in the posterior region. Forty implants of the XiVE(®) S plus screw type (DENTSPLY Friadent, Mannheim, Germany) were inserted in the posterior region of 24 patients and provided with zirconium dioxide abutments (FRIADENT(®) CERCON(®) Abutment, DENTSPLY Friadent). The following parameters were used to document the state of soft tissue: modified plaque index, modified sulcus bleeding index and pocket depth. Mesial and distal bone levels were determined on radiographs during the prosthetic treatment and at the 36-month recall. Thirty-seven implants could be followed up after 36 months in function. One patient wearing two abutments was lost to follow-up. One abutment exhibited a rotational misfit after 2 years in function. A further abutment showed the same failure at the 36-months recall appointment. In the remaining 36 implants the soft and hard tissue parameters were indicative of a low inflammatory status. Compared to the baseline situation, a partly significant bone apposition could be observed. Chipping of parts of the veneering ceramic was registered in 22% of the remaining implant restorations. The use of zirconia abutments in this study lead to mainly healthy peri-implant hard and soft tissue conditions but, considering the observed failures after 3 years in function, clinical long-term results should be awaited before recommending full zirconia implant abutments in a posterior indication.

  6. An expandable prosthesis with dual cage-and-plate function in a single device for vertebral body replacement: the clinical experience on 14 consecutive cases with vertebral tumors.

    Science.gov (United States)

    Ramírez, J J; Ramírez, J J; Chiquete, E; Gómez-Limón, E

    2011-09-01

    The aim of this paper was to test the hypothesis that an expandable prosthesis with dual cage-and-plate function can provide immediate and durable spine stabilization after corpectomy. We designed an expandable vertebral body prosthesis with dual cage-and-plate function in a single device (JR-prosthesis). Anatomical studies were performed to design a titanium-made prosthesis. Cadaver assays were done with a stainless steal device to test fixation and adequacy to the human spine anatomy. Then, 14 patients with vertebral tumors (8 metastatic) underwent corpectomy and vertebral body replacement with the JR-prosthesis. All patients had neurological deficit, severe pain and spine instability (mean follow-up: 25.4 months). Mean pain score before surgery in a visual analog scale improved from 7.6 to 3.0 points after operation (P=0.002). All patients achieved at least one grade of improvement in the Frankel score (P=0.003), excepting the 3 patients with Frankel grade A presurgery. Two patients with renal cell carcinoma died during the following 4 days after surgery (renal failure and massive bleeding), the rest attained a painless and stable spine immediately and maintained for long periods. No significant infections or implant failures were registered. A non-fatal case of inferior vena cava surgical injury was observed (repaired during surgery without further complications). The JR-prosthesis stabilizes the spine immediately after surgery and for the rest of the patients' life. To our knowledge, this is the first report on the clinical experience of any expandable vertebral body prosthesis with dual cage-and-plate function in a single device. These observations await confirmation in different scenarios.

  7. Association of blood pressure with decline in renal function and time until the start of renal replacement therapy in pre-dialysis patients: a cohort study

    Directory of Open Access Journals (Sweden)

    Sijpkens Yvo WJ

    2011-08-01

    Full Text Available Abstract Background To investigate whether high blood pressure accelerates renal function decline in patients with advanced chronic kidney disease (CKD, we studied the association of systolic (SBP and diastolic blood pressure (DBP with decline in renal function and time until the start of renal replacement therapy (RRT in patients with CKD stages IV-V on pre-dialysis care. Methods In the PREPARE-1 cohort 547 incident pre-dialysis patients, referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included between 1999 and 2001 and followed until the start of RRT, mortality, or end of follow-up (January 1st 2008. Main outcomes were rate of decline in renal function, estimated as the slope of available eGFR measurements, and time until the start of RRT. Results A total of 508 patients, 57% men and median (IQR age of 63 (50-73 years, were available for analyses. Mean (SD decline in renal function was 0.35 (0.75 ml/min/1.73 m2/month. Every 10 mmHg increase in SBP or DBP resulted in an accelerated decline in renal function (adjusted additional decline 0.04 (0.02;0.07 and 0.05 (0.00;0.11 ml/min/1.73 m2/month respectively and an earlier start of RRT (adjusted HR 1.09 (1.04;1.14 and 1.16 (1.05;1.28 respectively. Furthermore, patients with SBP and DBP above the BP target goal of 2/month and an earlier start of RRT (adjusted HR 2.08 (1.25;3.44, compared to patients who achieved the target goal (11%. Comparing the decline in renal function and risk of starting RRT between patients with only SBP above the target (≥ 130 mmHg and patients with both SBP and DBP below the target (2/month and adjusted HR 2.24 (1.26;3.97. Therefore, it seems that especially having SBP above the target is harmful. Conclusions In pre-dialysis patients with CKD stages IV-V, having blood pressure (especially SBP above the target goal for CKD patients (

  8. Functional Interplay between Type I and II Interferons Is Essential to Limit Influenza A Virus-Induced Tissue Inflammation.

    Directory of Open Access Journals (Sweden)

    Sebastian A Stifter

    2016-01-01

    Full Text Available Host control of influenza A virus (IAV is associated with exuberant pulmonary inflammation characterized by the influx of myeloid cells and production of proinflammatory cytokines including interferons (IFNs. It is unclear, however, how the immune system clears the virus without causing lethal immunopathology. Here, we demonstrate that in addition to its known anti-viral activity, STAT1 signaling coordinates host inflammation during IAV infection in mice. This regulatory mechanism is dependent on both type I IFN and IFN-γ receptor signaling and, importantly, requires the functional interplay between the two pathways. The protective function of type I IFNs is associated with not only the recruitment of classical inflammatory Ly6Chi monocytes into IAV-infected lungs, but also the prevention of excessive monocyte activation by IFN-γ. Unexpectedly, type I IFNs preferentially regulate IFN-γ signaling in Ly6Clo rather than inflammatory Ly6Chi mononuclear cell populations. In the absence of type I IFN signaling, Ly6Clo monocytes/macrophages, become phenotypically and functionally more proinflammatory than Ly6Chi cells, revealing an unanticipated function of the Ly6Clo mononuclear cell subset in tissue inflammation. In addition, we show that type I IFNs employ distinct mechanisms to regulate monocyte and neutrophil trafficking. Type I IFN signaling is necessary, but not sufficient, for preventing neutrophil recruitment into the lungs of IAV-infected mice. Instead, the cooperation of type I IFNs and lymphocyte-produced IFN-γ is required to regulate the tissue neutrophilic response to IAV. Our study demonstrates that IFN interplay links innate and adaptive anti-viral immunity to orchestrate tissue inflammation and reveals an additional level of complexity for IFN-dependent regulatory mechanisms that function to prevent excessive immunopathology while preserving anti-microbial functions.

  9. ROS production is essential for the apoptotic function of E2F1 in pheochromocytoma and neuroblastoma cell lines.

    Directory of Open Access Journals (Sweden)

    Lilia Espada

    Full Text Available In this study we demonstrate that accumulation of reactive oxygen species (ROS is essential for E2F1 mediated apoptosis in ER-E2F1 PC12 pheochromocytoma, and SH-SY5Y and SK-N-JD neuroblastoma stable cell lines. In these cells, the ER-E2F1 fusion protein is expressed in the cytosol; the addition of 4-hydroxytamoxifen (OHT induces its translocation to the nucleus and activation of E2F1target genes. Previously we demonstrated that, in ER-E2F1 PC12 cells, OHT treatment induced apoptosis through activation of caspase-3. Here we show that caspase-8 activity did not change upon treatment with OHT. Moreover, over-expression of Bcl-xL arrested OHT-induced apoptosis; by contrast, over-expression of c-FLIP, did not have any effect on OHT-induced apoptosis. OHT addition induces BimL expression, its translocation to mitochondria and activation of Bax, which is paralleled by diminished mitochondrial enrichment of Bcl-xL. Treatment with a Bax-inhibitory peptide reduced OHT-induced apoptosis. These results point out the essential role of mitochondria on the apoptotic process driven by E2F1. ROS accumulation followed E2F1 induction and treatment with the antioxidant N-acetylcysteine, inhibited E2F1-induced Bax translocation to mitochondria and subsequent apoptosis. The role of ROS in mediating OHT-induced apoptosis was also studied in two neuroblastoma cell lines, SH-SY5Y and SK-N-JD. In SH-SY5Y cells, activation of E2F1 by the addition of OHT induced ROS production and apoptosis, whereas over-expression of E2F1 in SK-N-JD cells failed to induce either response. Transcriptional profiling revealed that many of the genes responsible for scavenging ROS were down-regulated following E2F1-induction in SH-SY5Y, but not in SK-N-JD cells. Finally, inhibition of GSK3β blocked ROS production, Bax activation and the down regulation of ROS scavenging genes. These findings provide an explanation for the apparent contradictory role of E2F1 as an apoptotic agent versus a cell

  10. Mitochondrial histone-like DNA-binding proteins are essential for normal cell growth and mitochondrial function in Crithidia fasciculata

    Czech Academy of Sciences Publication Activity Database

    Avliyakulov, N. K.; Lukeš, Julius; Ray, D. S.

    2004-01-01

    Roč. 3, č. 2 (2004), s. 518-526 ISSN 1535-9778 R&D Projects: GA AV ČR IAA5022302 Institutional research plan: CEZ:AV0Z6022909 Keywords : cell growth * mitochondrial function * Kinetoplastida Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.954, year: 2004

  11. Management of functional Sprint Fidelis leads at cardiac resynchronization therapy-defibrillator generator replacement: a novel option for preventing inappropriate shocks from lead failure in fragile patients with high risk of sudden death.

    Science.gov (United States)

    Zhu, Dennis W X; Chu, Matthew M; House, Chad M

    2017-12-01

    In patients with a functional Sprint Fidelis lead at generator replacement, the manufacturer recommended to either continue to use the existing lead or replace it with a new lead. For those patients who continue to use a functional Fidelis lead, the risk of inappropriate shocks remains present if the lead fails in the future. We evaluated the feasibility of an alternative approach at the time of cardiac resynchronization therapy-defibrillator (CRT-D) generator replacement in patients with a functional bipolar left ventricular (LV) lead for prevention of inappropriate shocks from future Fidelis lead failure. During the procedure, the pace/sense IS-1 connection pin of the functional Fidelis lead was intentionally inserted into the LV port of the new CRT-D generator, while the existing bipolar LV lead IS-1 connection pin was inserted into the right ventricular (RV) pace/sense port. After such switching, the existing bipolar LV lead was used for functional LV pacing/sensing, while the Fidelis lead was used for functional RV pacing and high voltage shock only and could no longer be used for the purpose of sensing and detecting. This approach precluded oversensing and inappropriate shocks should the functional Fidelis lead fail in the future. Six fragile patients, who were not considered suitable candidates for lead replacement, underwent the alternative approach. During a follow-up of 35 ± 23 months, the CRT-D system functioned normally in five patients. The Fidelis lead fractured in one patient 7 months after generator replacement. The malfunction was detected promptly and the defected lead was replaced. No inappropriate detections or shock was triggered. In CRT-D patients with a functional Fidelis lead and a bipolar LV lead, switching of the Fidelis lead pace/sense IS-1 pin with the bipolar LV lead IS-1 pin at generator replacement did not affect normal system function. This novel approach may be valuable in fragile patients with high risk of sudden death for

  12. Nicotine replacement therapy

    Science.gov (United States)

    Smoking cessation - nicotine replacement; Tobacco - nicotine replacement therapy ... Before you start using a nicotine replacement product, here are some things to know: The more cigarettes you smoke, the higher the dose you may need to ...

  13. Hip Replacement Surgery

    Science.gov (United States)

    ... Initiative Breadcrumb Home Health Topics English Español Hip Replacement Surgery Basics In-Depth Download Download EPUB Download ... What is it? Points To Remember About Hip Replacement Surgery Hip replacement surgery removes damaged or diseased ...

  14. Valve Repair or Replacement

    Science.gov (United States)

    ... Replacement Menu Topics Topics FAQs Valve Repair or Replacement Heart valves play a key role in this ... leaflets with a tissue patch. What is valve replacement? Severe valve damage means the valve must be ...

  15. Transcatheter aortic valve replacement

    Science.gov (United States)

    ... gov/ency/article/007684.htm Transcatheter aortic valve replacement To use the sharing features on this page, please enable JavaScript. Transcatheter aortic valve replacement (TAVR) is surgery to replace the aortic valve. ...

  16. Knee joint replacement - discharge

    Science.gov (United States)

    ... Knee replacement - total - discharge; Tricompartmental knee replacement - discharge; Osteoarthritis - knee replacement discharge ... such as downhill skiing or contact sports like football and soccer. But, you should be able to ...

  17. Taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured primary brown and brite/beige adipocytes.

    Science.gov (United States)

    Li, Yongguo; Fromme, Tobias; Schweizer, Sabine; Schöttl, Theresa; Klingenspor, Martin

    2014-10-01

    Thermogenesis in brown adipocytes, conferred by mitochondrial uncoupling protein 1 (UCP1), is receiving great attention because metabolically active brown adipose tissue may protect humans from metabolic diseases. In particular, the thermogenic function of brown-like adipocytes in white adipose tissue, known as brite (or beige) adipocytes, is currently of prime interest. A valid procedure to quantify the specific contribution of UCP1 to thermogenesis is thus of vital importance. Adrenergic stimulation of lipolysis is a common way to activate UCP1. We here report, however, that in this frequently applied setup, taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured brown and brite adipocytes. By the application of these findings, we demonstrate that UCP1 is functionally thermogenic in intact brite adipocytes and adrenergic UCP1 activation is largely dependent on adipose triglyceride lipase (ATGL) rather than hormone sensitive lipase (HSL). © 2014 The Authors.

  18. Essential Tremor

    Science.gov (United States)

    ... of botulinum toxin as a treatment for a variety of involuntary movement disorders, including essential tremor of the hand. Get information from the National Library of Medicine’s MedlinePlus Tremor Show More Show Less Search Disorders SEARCH SEARCH Definition ...

  19. Highcharts essentials

    CERN Document Server

    Shahid, Bilal

    2014-01-01

    If you are a web developer with a basic knowledge of HTML, CSS, and JavaScript and want to quickly get started with this web charting technology, this is the book for you. This book will also serve as an essential guide to those who have probably used a similar library and are now looking at migrating to Highcharts.

  20. Swift essentials

    CERN Document Server

    Blewitt, Alex

    2014-01-01

    Whether you are a seasoned Objective-C developer or new to the Xcode platform, Swift Essentials will provide you with all you need to know to get started with the language. Prior experience with iOS development is not necessary, but will be helpful to get the most out of the book.

  1. The activation loop of PIP5K functions as a membrane sensor essential for lipid substrate processing

    Science.gov (United States)

    Liu, Aizhuo; Sui, Dexin; Wu, Dianqing; Hu, Jian

    2016-01-01

    Phosphatidylinositol 4-phosphate 5-kinase (PIP5K), a representative member of the phosphatidylinositol phosphate kinase (PIPK) family, is a major enzyme that biosynthesizes the signaling molecule PI(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) in eukaryotic cells. The stringent specificity toward lipid substrates and the high sensitivity to the membrane environment strongly suggest a membrane-sensing mechanism, but the underlying structural basis is still largely unknown. We present a nuclear magnetic resonance (NMR) study on a peptide commensurate with a PIP5K’s activation loop, which has been reported to be a determinant of lipid substrate specificity and subcellular localization of PIP5K. Although the activation loop is severely disordered in the crystal structure of PIP5K, the NMR experiments showed that the largely unstructured peptide folded into an amphipathic helix upon its association with the 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) micellar surface. Systematic mutagenesis and functional assays further demonstrated the crucial roles of the amphipathic helix and its hydrophobic surface in kinase activity and membrane-sensing function, supporting a working model in which the activation loop is a critical structural module conferring a membrane-sensing mechanism on PIP5K. The activation loop, surprisingly functioning as a membrane sensor, represents a new paradigm of kinase regulation by the activation loop through protein-membrane interaction, which also lays a foundation on the regulation of PIP5K (and other PIPKs) by membrane lipids for future studies. PMID:28138522

  2. The lysosomal enzyme receptor protein (LERP is not essential, but is implicated in lysosomal function in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Medina Hasanagic

    2015-10-01

    Full Text Available The lysosomal enzyme receptor protein (LERP of Drosophila melanogaster is the ortholog of the mammalian cation-independent mannose 6-phosphate (Man 6-P receptor, which mediates trafficking of newly synthesized lysosomal acid hydrolases to lysosomes. However, flies lack the enzymes necessary to make the Man 6-P mark, and the amino acids implicated in Man 6-P binding by the mammalian receptor are not conserved in LERP. Thus, the function of LERP in sorting of lysosomal enzymes to lysosomes in Drosophila is unclear. Here, we analyze the consequence of LERP depletion in S2 cells and intact flies. RNAi-mediated knockdown of LERP in S2 cells had little or no effect on the cellular content or secretion of several lysosomal hydrolases. We generated a novel Lerp null mutation, LerpF6, which abolishes LERP protein expression. Lerp mutants have normal viability and fertility and display no overt phenotypes other than reduced body weight. Lerp mutant flies exhibit a 30–40% decrease in the level of several lysosomal hydrolases, and are hypersensitive to dietary chloroquine and starvation, consistent with impaired lysosome function. Loss of LERP also enhances an eye phenotype associated with defective autophagy. Our findings implicate Lerp in lysosome function and autophagy.

  3. Comparison of functionally orientated tooth replacement and removable partial dentures on the nutritional status of partially dentate older patients: a randomised controlled clinical trial.

    Science.gov (United States)

    McKenna, Gerald; Allen, P Finbarr; O'Mahony, Denis; Flynn, Albert; Cronin, Michael; DaMata, Cristiane; Woods, Noel

    2014-06-01

    The aims of this study were to conduct a randomised controlled clinical trial (RCT) of partially dentate older adults comparing functionally orientated treatment based on the SDA concept with conventional treatment using RPDs to replace missing natural teeth. The two treatment strategies were evaluated according to their impact on nutritional status measured using haematological biomarkers. A randomised controlled clinical trial (RCT) was conducted of partially dentate patients aged 65 years and older (Trial Registration no. ISRCTN26302774). Each patient provided haematological samples which were screened for biochemical markers of nutritional status. Each sample was tested in Cork University Hospital for serum Albumin, serum Cholesterol, Ferritin, Folate, Vitamin B12 and 25-hydroxycholecalciferol (Vitamin D). A mixed model analysis of covariance (ANCOVA) indicated that for Vitamin B12 (p=0.9392), serum Folate (p=0.5827), Ferritin (p=0.6964), Albumin (p=0.8179), Serum Total Cholesterol (p=0.3670) and Vitamin D (p=0.7666) there were no statistically significant differences recorded between the two treatment groups. According to the mixed model analysis of covariance (ANCOVA) for Vitamin D there was a significant difference between levels recorded at post-operative time points after treatment intervention (p=0.0470). There was an increase of 7% in 25-hydroxycholecalciferol levels recorded at 6 months compared to baseline (p=0.0172). There was no further change in recorded levels at 12 months (p=0.6482) and these increases were similar within the two treatment groups (p>0.05). The only measure which illustrated consistent significant improvements in nutritional status for either group were Vitamin D levels. However no significant difference was recorded between the two treatment groups. Functionally orientated prosthodontic rehabilitation for partially dentate older patients was no worse than conventional removable partial dentures in terms of impact on nutritional

  4. The evaluation of the predictors of left ventricular systolic function improvement in patients with severe aortic stenosis after aortic valve replacement

    Directory of Open Access Journals (Sweden)

    N.V. Ponych

    2017-03-01

    Full Text Available The aim – to evaluate clinical and echocardiographic predictors of the systolic function improvement in patients with aortic stenosis (AS and low left ventricular ejection fraction (LVEF after aortic valve replacement (AVR. Material and methods. One-center study analyzed data received at clinical and instrumental examination of 72 consecutively examined patients with severe aortic stenosis and systolic dysfunction (LVEF less than 45 % selected for AVR with or without coronary artery bypass grafting (CABG. The average age of patients was 62 (lower-upper quartiles 34–79 years. All patients underwent clinical and instrumental investigations, including transthoracic echocardiography and coronary angiography. Patients were retrospectively divided into two groups: 48 (66.76 % patients with left ventricular ejection fraction increased more than 30 % in the early post-surgery period, and 24 (33.3 % – less than 30 %. In 21 (29.2 % patients AVR was combined with CABG. Results. Group of patients with greater growth of LVEF was characterized by lower body mass index (p = 0.016, greater initial signs of heart failure (p = 0.019, less frequent arterial hypertension. In addition, patients with LVEF growth over 30 % had more pronounced decrease of initial EF, greater end-systolic volume (ESV index and changes of some indices of diastolic LV function. The smaller increase in LVEF was associated with greater rate of atrial fibrillation (p = 0.028 and aortic regurgitation I degree (p = 0.012. Conclusions. The median LVEF in patients with AS and systolic dysfunction after AVR increased from 29 to 43 %. Under proper selection of patients with AS and reduced LVEF for surgery more than 30 % improvement of LVEF may be expected at early postoperative period. Critical AS with reduced LVEF, including low-flow, low gradient AS should not be regarded as an independent restriction to AVR.

  5. Physical Function After Total Knee Replacement: An Observational Study Describing Outcomes in a Small Group of Women From China and the United States.

    Science.gov (United States)

    White, Daniel K; Li, Zhichang; Zhang, Yuqing; Marmon, Adam R; Master, Hiral; Zeni, Joseph; Niu, Jingbo; Jiang, Long; Zhang, Shu; Lin, Jianhao

    2018-01-01

    To describe physical function before and six months after Total Knee Replacement (TKR) in a small sample of women from China and the United States. Observational. Community environment. Both groups adhered to the Osteoarthritis Research Society International (OARSI) protocols for the 6-minute walk and 30-second chair stand. We compared physical function prior to TKR and 6 months after using linear regression adjusted for covariates. Women (N=60) after TKR. Not applicable. Age and body mass index in the China group (n=30; 66y and 27.0kg/m 2 ) were similar to those in the U.S. group (n=30; 65y and 29.6kg/m 2 ). Before surgery, the China group walked 263 (95% confidence interval [CI], -309 to -219) less meters and had 10.2 (95% CI, -11.8 to -8.5) fewer chair stands than the U.S. group. At 6 months when compared with the U.S. group, the China group walked 38 more meters, but this difference did not reach statistical significance (95% CI, -1.6 to 77.4), and had 3.1 (95% CI, -4.4 to -1.7) fewer chair stands. The China group had greater improvement in the 6-minute walk test than did the U.S. group (PChina group had greater gains in walking endurance and similar gains in repeated chair stands than did the U.S. group after surgery. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  6. UCI knee replacement.

    Science.gov (United States)

    Evanski, P M; Waugh, T R; Orofino, C F; Anzel, S H

    1976-10-01

    Between March 9, 1972 and December 31, 1973, a total of 103 UCI knee replacements were performed. Follow-up data are available on 83 knees with an average follow-up of 33 months. Patient evaluation of the end results indicates that 78.3 per cent were better, 9.6 per cent unchanged, and 12.1 per cent worse. Patient evaluation of their own knee function averaged 55 per cent preoperatively and 79 per cent postoperatively. Patients were also evaluated on a 100 point Modified Larson Analysis Form. The average preoperative score was 46, and the average postoperative score was 70. There were six (5.8%) biological complications in the 103 knee replacement. Biological complications included infections, wound healing problems and unexplained pain. Mechanical complications were seen in 18 (17.4%) knees, and included knee instability, tibial component loosening or deformation, and patellar problems. Additional surgery was required in 18 (17.4%) knees. Failure of the procedure eventually requiring removal of the prosthesis and fusion or amputation occurred in 4 (3.9%) knees. The intermediate-term results of UCI knee replacement have been clinically satisfactory. We currently recommend consideration of this procedure for patients with disabling arthritis of the knee.

  7. The functional interplay between protein kinase CK2 and CCA1 transcriptional activity is essential for clock temperature compensation in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Sergi Portolés

    2010-11-01

    Full Text Available Circadian rhythms are daily biological oscillations driven by an endogenous mechanism known as circadian clock. The protein kinase CK2 is one of the few clock components that is evolutionary conserved among different taxonomic groups. CK2 regulates the stability and nuclear localization of essential clock proteins in mammals, fungi, and insects. Two CK2 regulatory subunits, CKB3 and CKB4, have been also linked with the Arabidopsis thaliana circadian system. However, the biological relevance and the precise mechanisms of CK2 function within the plant clockwork are not known. By using ChIP and Double-ChIP experiments together with in vivo luminescence assays at different temperatures, we were able to identify a temperature-dependent function for CK2 modulating circadian period length. Our study uncovers a previously unpredicted mechanism for CK2 antagonizing the key clock regulator CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1. CK2 activity does not alter protein accumulation or subcellular localization but interferes with CCA1 binding affinity to the promoters of the oscillator genes. High temperatures enhance the CCA1 binding activity, which is precisely counterbalanced by the CK2 opposing function. Altering this balance by over-expression, mutation, or pharmacological inhibition affects the temperature compensation profile, providing a mechanism by which plants regulate circadian period at changing temperatures. Therefore, our study establishes a new model demonstrating that two opposing and temperature-dependent activities (CCA1-CK2 are essential for clock temperature compensation in Arabidopsis.

  8. Synergistic Function of E2F7 and E2F8 is Essential for Cell Survival and Embryonic Development

    OpenAIRE

    Li, Jing; Ran, Cong; Li, Edward; Gordon, Faye; Comstock, Grant; Siddiqui, Hasan; Cleghorn, Whitney; Chen, Hui-zi; Kornacker, Karl; Pandit, Shusil K.; Khanizadeh, Mehrbod; Weinstein, Michael; Leone, Gustavo; de Bruin, Alain

    2008-01-01

    The novel E2f7 and E2f8 family members are thought to function as transcriptional repressors important for the control of cell proliferation. Here we have analyzed the consequences of inactivating E2f7 and E2f8 in mice and show that their individual loss had no significant effect on development. Their combined ablation, however, resulted in massive apoptosis and dilation of blood vessels, culminating in lethality by embryonic day E11.5. A deficiency in E2f7 and E2f8 led to an increase in E2f1...

  9. Essential Bacillus subtilis genes

    DEFF Research Database (Denmark)

    Kobayashi, K.; Ehrlich, S.D.; Albertini, A.

    2003-01-01

    To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were...... predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related...... to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from...

  10. Sustained activation of STAT5 is essential for chromatin remodeling and maintenance of mammary-specific function

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ren; Nelson, Celeste M.; Muschler, John L.; Veiseh, Mandana; Vonderhaar, Barbara K.; Bissell, Mina J.

    2009-06-03

    Epithelial cells, once dissociated and placed in two-dimensional (2D) cultures, rapidly lose tissue-specific functions. We showed previously that in addition to prolactin, signaling by laminin-111 was necessary to restore functional differentiation of mammary epithelia. Here, we elucidate two additional aspects of laminin-111 action. We show that in 2D cultures, the prolactin receptor is basolaterally localized and physically segregated from its apically placed ligand. Detachment of the cells exposes the receptor to ligation by prolactin leading to signal transducers and activators of transcription protein 5 (STAT5) activation, but only transiently and not sufficiently for induction of milk protein expression. We show that laminin-111 reorganizes mammary cells into polarized acini, allowing both the exposure of the prolactin receptor and sustained activation of STAT5. The use of constitutively active STAT5 constructs showed that the latter is necessary and sufficient for chromatin reorganization and {beta}-casein transcription. These results underscore the crucial role of continuous laminin signaling and polarized tissue architecture in maintenance of transcription factor activation, chromatin organization, and tissue-specific gene expression.

  11. The relationship between cognitive function, depressive behaviour and sleep quality with 24-h urinary sodium excretion in patients with essential hypertension.

    Science.gov (United States)

    Afsar, Baris

    2013-03-01

    Various studies have shown that sodium intake is related to increased blood pressure. However, the relationship between sodium intake and cognitive function and depression has not previously been studied. The objective of this study was to investigate the relationship between 24-h sodium excretion with cognitive function, depression and sleep quality in patients newly diagnosed with essential hypertension. All patients underwent history taking, physical examination, blood pressure measurement, 12-lead ECG evaluation, routine urine analysis, biochemical analysis and 24-h urine collection to measure urinary sodium and protein excretion and creatinine clearance, evaluation of cognitive function, depressive behaviour and sleep quality. In total, 119 patients newly diagnosed with essential hypertension (50 men and 69 women aged 54.2 ± 16.1 years) were enrolled. The 24-h urinary sodium excretion of the patients was 204.0 ± 240.4 mEq/day. The Standardized Mini Mental State Examination (SMMSE), Pittsburgh Sleep Quality Index and Beck Depression Inventory scores of the patients were 26.0 ± 2.7, 5.6 ± 3.1 and 21.6 ± 13.5, respectively. Spearman correlation analysis revealed that 24-h urinary sodium excretion was correlated with age (rho -0.258, p = 0.005), systolic blood pressure (rho 0.219, p = 0.017), diastolic blood pressure (rho 0.195, p = 0.034), creatinine clearance (rho 0.414, p cognitive function, but not depressive behaviour and sleep disturbance, is related to decreased sodium intake as evaluated by 24-h urinary sodium excretion. Studies are needed to highlight the mechanisms regarding the relationship between cognitive function and sodium intake.

  12. Human telomerase reverse transcriptase (hTERT Q169 is essential for telomerase function in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Haley D M Wyatt

    Full Text Available BACKGROUND: Telomerase is a reverse transcriptase that maintains the telomeres of linear chromosomes and preserves genomic integrity. The core components are a catalytic protein subunit, the telomerase reverse transcriptase (TERT, and an RNA subunit, the telomerase RNA (TR. Telomerase is unique in its ability to catalyze processive DNA synthesis, which is facilitated by telomere-specific DNA-binding domains in TERT called anchor sites. A conserved glutamine residue in the TERT N-terminus is important for anchor site interactions in lower eukaryotes. The significance of this residue in higher eukaryotes, however, has not been investigated. METHODOLOGY/PRINCIPAL FINDINGS: To understand the significance of this residue in higher eukaryotes, we performed site-directed mutagenesis on human TERT (hTERT Q169 to create neutral (Q169A, conservative (Q169N, and non-conservative (Q169D mutant proteins. We show that these mutations severely compromise telomerase activity in vitro and in vivo. The functional defects are not due to abrogated interactions with hTR or telomeric ssDNA. However, substitution of hTERT Q169 dramatically impaired the ability of telomerase to incorporate nucleotides at the second position of the template. Furthermore, Q169 mutagenesis altered the relative strength of hTERT-telomeric ssDNA interactions, which identifies Q169 as a novel residue in hTERT required for optimal primer binding. Proteolysis experiments indicate that Q169 substitution alters the protease-sensitivity of the hTERT N-terminus, indicating that a conformational change in this region of hTERT is likely critical for catalytic function. CONCLUSIONS/SIGNIFICANCE: We provide the first detailed evidence regarding the biochemical and cellular roles of an evolutionarily-conserved Gln residue in higher eukaryotes. Collectively, our results indicate that Q169 is needed to maintain the hTERT N-terminus in a conformation that is necessary for optimal enzyme

  13. Cdh1 Is Essential for Endometrial Differentiation, Gland Development, and Adult Function in the Mouse Uterus1

    Science.gov (United States)

    Reardon, Sarah N.; King, Mandy L.; MacLean, James A.; Mann, Jordan L.; DeMayo, Francesco J.; Lydon, John P.; Hayashi, Kanako

    2012-01-01

    ABSTRACT CDH1 is a cell-cell adhesion molecule expressed in the epithelium to coordinate key morphogenetic processes, establish cell polarity, and regulate epithelial differentiation and proliferation. To determine the role of CDH1 in the mouse uterus, Cdh1 was conditionally ablated by crossing Pgr-Cre and Cdh1-flox mice, and the phenotype was characterized. We found that loss of Cdh1 results in a disorganized cellular structure of the epithelium and ablation of endometrial glands in the neonatal uterus. Cdh1d/d mice lost adherens junctions (CTNNB1 and CTNNA1) and tight junctions (claudin, occludin, and ZO-1 proteins) in the neonatal uterus, leading to loss of epithelial cell-cell interaction. Ablation of Cdh1 induced abnormal epithelial proliferation and massive apoptosis, and disrupted Wnt and Hox gene expression in the neonatal uterus. Although the uteri of Cdh1d/d mice did not show any myometrial defects, ablation of Cdh1 inhibited expression of epithelial (cytokeratin 8) and stromal (CD10) markers. Cdh1d/d mice were infertile because of defects during implantation and decidualization. Furthermore, we showed in the model of conditional ablation of both Cdh1 and Trp53 in the uterus that interrupting cell cycle regulation through the loss of Cdh1 leads to abnormal uterine development. The uteri of Cdh1d/d Trp53d/d mice exhibited histological features of endometrial carcinomas with myometrial invasion. Collectively, these findings suggest that CDH1 has an important role in structural and functional development of the uterus as well as adult uterine function. CDH1 has a capacity to control cell fate by altering directional cell proliferation and apoptosis. PMID:22378759

  14. Prolactin receptor signaling is essential for perinatal brown adipocyte function: a role for insulin-like growth factor-2.

    Directory of Open Access Journals (Sweden)

    Say Viengchareun

    2008-02-01

    Full Text Available The lactogenic hormones prolactin (PRL and placental lactogens (PL play central roles in reproduction and mammary development. Their actions are mediated via binding to PRL receptor (PRLR, highly expressed in brown adipose tissue (BAT, yet their impact on adipocyte function and metabolism remains unclear.PRLR knockout (KO newborn mice were phenotypically characterized in terms of thermoregulation and their BAT differentiation assayed for gene expression studies. Derived brown preadipocyte cell lines were established to evaluate the molecular mechanisms involved in PRL signaling on BAT function. Here, we report that newborn mice lacking PRLR have hypotrophic BAT depots that express low levels of adipocyte nuclear receptor PPARgamma2, its coactivator PGC-1alpha, uncoupling protein 1 (UCP1 and the beta3 adrenoceptor, reducing mouse viability during cold challenge. Immortalized PRLR KO preadipocytes fail to undergo differentiation into mature adipocytes, a defect reversed by reintroduction of PRLR. That the effects of the lactogens in BAT are at least partly mediated by Insulin-like Growth Factor-2 (IGF-2 is supported by: i a striking reduction in BAT IGF-2 expression in PRLR KO mice and in PRLR-deficient preadipocytes; ii induction of cellular IGF-2 expression by PRL through JAK2/STAT5 pathway activation; and iii reversal of defective differentiation in PRLR KO cells by exogenous IGF-2.Our findings demonstrate that the lactogens act in concert with IGF-2 to control brown adipocyte differentiation and growth. Given the prominent role of brown adipose tissue during the perinatal period, our results identified prolactin receptor signaling as a major player and a potential therapeutic target in protecting newborn mammals against hypothermia.

  15. Akt1 is essential for postnatal mammary gland development, function, and the expression of Btn1a1.

    Directory of Open Access Journals (Sweden)

    Jessica LaRocca

    Full Text Available Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays critical roles in the regulation of multiple cellular processes, and has previously been implicated in lactation and breast cancer development. In this study, we utilized Akt1+/+ and Akt1-/- C57/Bl6 female mice to assess the role that Akt1 plays in normal mammary gland postnatal development and function. We examined postnatal morphology at multiple time points, and analyzed gene and protein expression changes that persist into adulthood. Akt1 deficiency resulted in several mammary gland developmental defects, including ductal outgrowth and defective terminal end bud formation. Adult Akt1-/- mammary gland composition remained altered, exhibiting fewer alveolar buds coupled with increased epithelial cell apoptosis. Microarray analysis revealed that Akt1 deficiency altered expression of genes involved in numerous biological processes in the mammary gland, including organismal development, cell death, and tissue morphology. Of particular importance, a significant decrease in expression of Btn1a1, a gene involved in milk lipid secretion, was observed in Akt1-/- mammary glands. Additionally, pseudopregnant Akt1-/- females failed to induce Btn1a1 expression in response to hormonal stimulation compared to their wild-type counterparts. Retroviral-mediated shRNA knockdown of Akt1 and Btn1a1 in MCF-7 human breast epithelial further illustrated the importance of Akt1 in mammary epithelial cell proliferation, as well as in the regulation of Btn1a1 and subsequent expression of ß-casein, a gene that encodes for milk protein. Overall these findings provide mechanistic insight into the role of Akt1 in mammary morphogenesis and function.

  16. C programming language essentials

    CERN Document Server

    Ackermann, Ernest C

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. C Programming Language discusses fundamental notions, data types and objects, expressions, statements, declarations, function and program structure, the preprocessor, and the standar

  17. Set theory essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Set Theory includes elementary logic, sets, relations, functions, denumerable and non-denumerable sets, cardinal numbers, Cantor's theorem, axiom of choice, and order relations.

  18. Laplace transforms essentials

    CERN Document Server

    Shafii-Mousavi, Morteza

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Laplace Transforms includes the Laplace transform, the inverse Laplace transform, special functions and properties, applications to ordinary linear differential equations, Fourier tr

  19. The region of XRCC1 which harbours the three most common nonsynonymous polymorphic variants, is essential for the scaffolding function of XRCC1

    DEFF Research Database (Denmark)

    Hanssen-Bauer, Audun; Solvang-Garten, Karin; Gilljam, Karin Margaretha

    2012-01-01

    for recruitment of XRCC1 to sites of DNA damage and DNA replication. Also, we found that ectopic expression of the region from residue 166-436 partially rescued the methyl methanesulfonate (MMS) hypersensitivity of XRCC1-deficient EM9 cells, suggesting a key role for this region in mediating DNA repair. The three...... most common amino acid variants of XRCC1, Arg194Trp, Arg280His and Arg399Gln, are located within the region comprising the NLS and BRCT1 domains, and these variants may be associated with increased incidence of specific types of cancer. While we could not detect differences in the intra......XRCC1 functions as a non-enzymatic, scaffold protein in single strand break repair (SSBR) and base excision repair (BER). Here, we examine different regions of XRCC1 for their contribution to the scaffolding functions of the protein. We found that the central BRCT1 domain is essential...

  20. Defining line replaceable units

    NARCIS (Netherlands)

    Parada Puig, J.E.; Basten, Robertus Johannes Ida

    2015-01-01

    Defective capital assets may be quickly restored to their operational condition by replacing the item that has failed. The item that is replaced is called the Line Replaceable Unit (LRU), and the so-called LRU definition problem is the problem of deciding on which item to replace upon each type of

  1. Influence of Laser-Lok surface on immediate functional loading of implants in single-tooth replacement: a 2-year prospective clinical study.

    Science.gov (United States)

    Farronato, Davide; Mangano, Francesco; Briguglio, Francesco; Iorio-Siciliano, Vincenzo; Riccitiello, Francesco; Guarnieri, Renzo

    2014-01-01

    The purpose of this study was to evaluate the influence of a Laser-Lok microtexturing surface on clinical attachment level and crestal bone remodeling around immediately functionally loaded implants in single-tooth replacement. Seventy-seven patients were included in a prospective, randomized study and divided into two groups. Group 1 (control) consisted of non-Laser-Lok type implants (n = 39), while in group 2 (test), Laser-Lok type implants were used (n = 39). Crestal bone loss (CBL) and clinical parameters including clinical attachment level (CAL), Plaque Index (PI), and bleeding on probing were recorded at baseline examinations and at 6, 12, and 24 months after loading with the final restoration. One implant was lost in the control group and one in the test group, giving a total survival rate of 96.1% after 2 years. PI and BOP outcomes were similar for both implant types without statistical differences. A mean CAL loss of 1.10 ± 0.51 mm was observed during the first 2 years in group 1, while the mean CAL loss observed in group 2 was 0.56 ± 0.33 mm. Radiographically, group 1 implants showed a mean crestal bone loss of 1.07 ± 0.30 mm compared with 0.49 ± 0.34 mm for group 2. The type of implant did not influence the survival rate, whereas Laser-Lok implants resulted in greater CAL and in shallower radiographic peri-implant CBL than non-Laser-Lok implants.

  2. Patients with severe radiographic osteoarthritis have a better prognosis in physical functioning after hip and knee replacement: a cohort-study.

    Directory of Open Access Journals (Sweden)

    J Christiaan Keurentjes

    Full Text Available INTRODUCTION: Although Total Hip and Knee Replacements (THR/TKR improve Health-Related Quality of Life (HRQoL at the group level, up to 30% of patients are dissatisfied after surgery due to unfulfilled expectations. We aimed to assess whether the pre-operative radiographic severity of osteoarthritis (OA is related to the improvement in HRQoL after THR or TKR, both at the population and individual level. METHODS: In this multi-center observational cohort study, HRQoL of OA patients requiring THR or TKR was measured 2 weeks before surgery and at 2-5 years follow-up, using the Short-Form 36 (SF36. Additionally, we measured patient satisfaction on a 11-point Numeric Rating Scale (NRSS. The radiographic severity of OA was classified according to Kellgren and Lawrence (KL by an independent experienced musculoskeletal radiologist, blinded for the outcome. We compared the mean improvement and probability of a relevant improvement (defined as a patients change score ≥ Minimal Clinically Important Difference between patients with mild OA (KL Grade 0-2 and severe OA (KL Grade 3+4, whilst adjusting for confounders. RESULTS: Severe OA patients improved more and had a higher probability of a relevant improvement in physical functioning after both THR and TKR. For TKR patients with severe OA, larger improvements were found in General Health, Vitality and the Physical Component Summary Scale. The mean NRSS was also higher in severe OA TKR patients. DISCUSSION: Patients with severe OA have a better prognosis after THR and TKR than patients with mild OA. These findings might help to prevent dissatisfaction after THR and TKR by means of patient selection or expectation management.

  3. Replacement of the endogenous starch debranching enzymes ISA1 and ISA2 of Arabidopsis with the rice orthologs reveals a degree of functional conservation during starch synthesis.

    Directory of Open Access Journals (Sweden)

    Sebastian Streb

    Full Text Available This study tested the interchangeability of enzymes in starch metabolism between dicotyledonous and monocotyledonous plant species. Amylopectin--a branched glucose polymer--is the major component of starch and is responsible for its semi-crystalline property. Plants synthesize starch with distinct amylopectin structures, varying between species and tissues. The structure determines starch properties, an important characteristic for cooking and nutrition, and for the industrial uses of starch. Amylopectin synthesis involves at least three enzyme classes: starch synthases, branching enzymes and debranching enzymes. For all three classes, several enzyme isoforms have been identified. However, it is not clear which enzyme(s are responsible for the large diversity of amylopectin structures. Here, we tested whether the specificities of the debranching enzymes (ISA1 and ISA2 are major determinants of species-dependent differences in amylopectin structure by replacing the dicotyledonous Arabidopsis isoamylases (AtISA1 and AtISA2 with the monocotyledonous rice (Oryza sativa isoforms. We demonstrate that the ISA1 and ISA2 are sufficiently well conserved between these species to form heteromultimeric chimeric Arabidopsis/rice isoamylase enzymes. Furthermore, we were able to reconstitute the endosperm-specific rice OsISA1 homomultimeric complex in Arabidopsis isa1isa2 mutants. This homomultimer was able to facilitate normal rates of starch synthesis. The resulting amylopectin structure had small but significant differences in comparison to wild-type Arabidopsis amylopectin. This suggests that ISA1 and ISA2 have a conserved function between plant species with a major role in facilitating the crystallization of pre-amylopectin synthesized by starch synthases and branching enzymes, but also influencing the final structure of amylopectin.

  4. Replacement of the endogenous starch debranching enzymes ISA1 and ISA2 of Arabidopsis with the rice orthologs reveals a degree of functional conservation during starch synthesis.

    Science.gov (United States)

    Streb, Sebastian; Zeeman, Samuel C

    2014-01-01

    This study tested the interchangeability of enzymes in starch metabolism between dicotyledonous and monocotyledonous plant species. Amylopectin--a branched glucose polymer--is the major component of starch and is responsible for its semi-crystalline property. Plants synthesize starch with distinct amylopectin structures, varying between species and tissues. The structure determines starch properties, an important characteristic for cooking and nutrition, and for the industrial uses of starch. Amylopectin synthesis involves at least three enzyme classes: starch synthases, branching enzymes and debranching enzymes. For all three classes, several enzyme isoforms have been identified. However, it is not clear which enzyme(s) are responsible for the large diversity of amylopectin structures. Here, we tested whether the specificities of the debranching enzymes (ISA1 and ISA2) are major determinants of species-dependent differences in amylopectin structure by replacing the dicotyledonous Arabidopsis isoamylases (AtISA1 and AtISA2) with the monocotyledonous rice (Oryza sativa) isoforms. We demonstrate that the ISA1 and ISA2 are sufficiently well conserved between these species to form heteromultimeric chimeric Arabidopsis/rice isoamylase enzymes. Furthermore, we were able to reconstitute the endosperm-specific rice OsISA1 homomultimeric complex in Arabidopsis isa1isa2 mutants. This homomultimer was able to facilitate normal rates of starch synthesis. The resulting amylopectin structure had small but significant differences in comparison to wild-type Arabidopsis amylopectin. This suggests that ISA1 and ISA2 have a conserved function between plant species with a major role in facilitating the crystallization of pre-amylopectin synthesized by starch synthases and branching enzymes, but also influencing the final structure of amylopectin.

  5. Esrrg functions in early branch generation of the ureteric bud and is essential for normal development of the renal papilla.

    Science.gov (United States)

    Berry, Rachel; Harewood, Louise; Pei, Liming; Fisher, Malcolm; Brownstein, David; Ross, Allyson; Alaynick, William A; Moss, Julie; Hastie, Nicholas D; Hohenstein, Peter; Davies, Jamie A; Evans, Ronald M; FitzPatrick, David R

    2011-03-01

    Congenital anomalies of the kidney and urinary tract (CAKUTs) are common disorders of human development affecting the renal parechyma, renal pelvis, ureter, bladder and urethra; they show evidence of shared genetic aetiology, although the molecular basis of this remains unknown in the majority of cases. Breakpoint mapping of a de novo, apparently balanced, reciprocal translocation associated with bilateral renal agenesis has implicated the gene encoding the nuclear steroid hormone receptor ESRRG as a candidate gene for CAKUT. Here we show that the Esrrg protein is detected throughout early ureteric ducts as cytoplasmic/sub-membranous staining; with nuclear localization seen in developing nephrons. In 14.5-16.5 dpc (days post-conception) mouse embryos, Esrrg localizes to the subset of ductal tissue within the kidney, liver and lung. The renal ductal expression becomes localized to renal papilla by 18.5 dpc. Perturbation of function was performed in embryonic mouse kidney culture using pooled siRNA to induce knock-down and a specific small-molecule agonist to induce aberrant activation of Esrrg. Both resulted in severe abnormality of early branching events of the ureteric duct. Mouse embryos with a targeted inactivation of Esrrg on both alleles (Esrrg(-/-)) showed agenesis of the renal papilla but normal development of the cortex and remaining medulla. Taken together, these results suggest that Esrrg is required for early branching events of the ureteric duct that occur prior to the onset of nephrogenesis. These findings confirm ESRRG as a strong candidate gene for CAKUT.

  6. Essential Structural and Functional Roles of the Cmr4 Subunit in RNA Cleavage by the Cmr CRISPR-Cas Complex

    Directory of Open Access Journals (Sweden)

    Nancy F. Ramia

    2014-12-01

    Full Text Available The Cmr complex is the multisubunit effector complex of the type III-B clustered regularly interspaced short palindromic repeats (CRISPR-Cas immune system. The Cmr complex recognizes a target RNA through base pairing with the integral CRISPR RNA (crRNA and cleaves the target at multiple regularly spaced locations within the complementary region. To understand the molecular basis of the function of this complex, we have assembled information from electron microscopic and X-ray crystallographic structural studies and mutagenesis of a complete Pyrococcus furiosus Cmr complex. Our findings reveal that four helically packed Cmr4 subunits, which make up the backbone of the Cmr complex, act as a platform to support crRNA binding and target RNA cleavage. Interestingly, we found a hook-like structural feature associated with Cmr4 that is likely the site of target RNA binding and cleavage. Our results also elucidate analogies in the mechanisms of crRNA and target molecule binding by the distinct Cmr type III-A and Cascade type I-E complexes.

  7. Synergistic Function of E2F7 and E2F8 is Essential for Cell Survival and Embryonic Development

    Science.gov (United States)

    Li, Jing; Ran, Cong; Li, Edward; Gordon, Faye; Comstock, Grant; Siddiqui, Hasan; Cleghorn, Whitney; Chen, Hui-zi; Kornacker, Karl; Pandit, Shusil K.; Khanizadeh, Mehrbod; Weinstein, Michael; Leone, Gustavo; de Bruin, Alain

    2008-01-01

    Summary The novel E2f7 and E2f8 family members are thought to function as transcriptional repressors important for the control of cell proliferation. Here we have analyzed the consequences of inactivating E2f7 and E2f8 in mice and show that their individual loss had no significant effect on development. Their combined ablation, however, resulted in massive apoptosis and dilation of blood vessels, culminating in lethality by embryonic day E11.5. A deficiency in E2f7 and E2f8 led to an increase in E2f1 and p53, as well as in many stress-related genes. Homo- and hetero-dimers of E2F7 and E2F8 were found on target promoters, including E2f1. Importantly, loss of either E2f1 or p53 suppressed the massive apoptosis in double mutant embryos. These results identify E2F7 and E2F8 as a unique repressive arm of the E2F transcriptional network that is critical for embryonic development and control of the E2F1-p53 apoptotic axis. PMID:18194653

  8. Docosahexaenoic acid (DHA, an essential fatty acid for the proper functioning of neuronal cells: their role in mood disorders

    Directory of Open Access Journals (Sweden)

    2009-06-01

    Full Text Available The brain and the nervous system are tissues with high contents of two polyunsaturated fatty acids: arachidonic acid (20:4, omega-6, AA and docosahexaenoic acid (22:6, omega-3, DHA. Despite their abundance in these tissues, AA and DHA cannot be re-synthesized in mammals. However, the concentration of these fatty acids can be modulated by dietary intake. AA and DHA must be provided by the diet as such (preformed or through the respective omega-6 and omega-3 precursors from vegetable origin. Linoleic acid, the precursor of AA is very abundant in the western diet and therefore the formation of AA from linoleic acid is not restrictive. On the other hand, alpha linolenic acid, the precursor of DHA is less available in our diet and preformed DHA is highly restrictive in some populations. During the last period of gestation and during the early post natal period, neurodevelopment occurs exceptionally quickly, and significant amounts of omega-6 and omega-3 polyunsaturated fatty acids, especially DHA, are critical to allow neurite outgrowth and the proper brain and retina development and function. In this review various functions of DHA in the nervous system, its metabolism into phospholipids, and its involvement in different neurological and mood disorders, such as Alzheimer’s disease, depression, and others are revised.

    El cerebro y el sistema nervioso son tejidos con un alto contenido de dos ácidos grasos poliinsaturados: el ácido araquidónico (20:4, omega-6, AA y el ácido docosahexaenoico (22:6, omega-3, DHA. A pesar de la abundancia de estos ácidos grasos en dichos tejidos los mamíferos no los pueden sintetizar de novo. Sin embargo, la concentración de estos ácidos grasos puede ser modificada por la dieta. El AA y el DHA pueden ser aportados por la dieta como tales (preformados o a partir de los respectivos precursores de origen vegetal. El ácido linoleico, precursor del AA es muy abundante en la dieta occidental, por lo cual la

  9. Functional and structural insights revealed by molecular dynamics simulations of an essential RNA editing ligase in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Rommie E Amaro

    2007-11-01

    Full Text Available RNA editing ligase 1 (TbREL1 is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei, the parasite responsible for the devastating tropical disease African sleeping sickness. The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes, and no close human homolog is known to exist. In addition, the high-resolution crystal structure revealed several unique features of the active site, making this enzyme a promising target for structure-based drug design. In this work, two 20 ns atomistic molecular dynamics (MD simulations are employed to investigate the dynamics of TbREL1, both with and without the ATP substrate present. The flexibility of the active site, dynamics of conserved residues and crystallized water molecules, and the interactions between TbREL1 and the ATP substrate are investigated and discussed in the context of TbREL1's function. Differences in local and global motion upon ATP binding suggest that two peripheral loops, unique to the trypanosomes, may be involved in interdomain signaling events. Notably, a significant structural rearrangement of the enzyme's active site occurs during the apo simulations, opening an additional cavity adjacent to the ATP binding site that could be exploited in the development of effective inhibitors directed against this protozoan parasite. Finally, ensemble averaged electrostatics calculations over the MD simulations reveal a novel putative RNA binding site, a discovery that has previously eluded scientists. Ultimately, we use the insights gained through the MD simulations to make several predictions and recommendations, which we anticipate will help direct future experimental studies and structure-based drug discovery efforts against this vital enzyme.

  10. Essential SQLAlchemy

    CERN Document Server

    Copeland, Rick

    2008-01-01

    Essential SQLAlchemy introduces a high-level open-source code library that makes it easier for Python programmers to access relational databases such as Oracle, DB2, MySQL, PostgreSQL, and SQLite. SQLAlchemy has become increasingly popular since its release, but it still lacks good offline documentation. This practical book fills the gap, and because a developer wrote it, you get an objective look at SQLAlchemy's tools rather than an advocate's description of all the "cool" features. SQLAlchemy includes both a database server-independent SQL expression language and an object-relational mappe

  11. Linux Essentials

    CERN Document Server

    Smith, Roderick W

    2012-01-01

    A unique, full-color introduction to Linux fundamentals Serving as a low-cost, secure alternative to expensive operating systems, Linux is a UNIX-based, open source operating system. Full-color and concise, this beginner's guide takes a learning-by-doing approach to understanding the essentials of Linux. Each chapter begins by clearly identifying what you will learn in the chapter, followed by a straightforward discussion of concepts that leads you right into hands-on tutorials. Chapters conclude with additional exercises and review questions, allowing you to reinforce and measure your underst

  12. Prezi essentials

    CERN Document Server

    Sinclair, Domi

    2014-01-01

    If you want to learn Prezi, and specifically design within Prezi, this is the book for you. Perhaps you already know a bit about Prezi but have never used it, or perhaps you have used Prezi before but want to learn how to incorporate your own custom design elements. In either case, this book will get you up and running quickly. It would be helpful to have a bit of familiarity with basic design concepts and the use of Prezi, but prior experience is not essential.

  13. Human Adenovirus Core Protein V Is Targeted by the Host SUMOylation Machinery To Limit Essential Viral Functions.

    Science.gov (United States)

    Freudenberger, Nora; Meyer, Tina; Groitl, Peter; Dobner, Thomas; Schreiner, Sabrina

    2018-02-15

    concept needs expansion as the functions are more diverse. We showed that capsid protein VI regulates the antiviral response by modulation of the transcription factor Daxx during infection. Moreover, core protein VII interacts with SPOC1 restriction factor, which is beneficial for efficient viral gene expression. Here, we were able to show that core protein V also represents a novel substrate of the host SUMOylation machinery and contains several conserved SCMs; mutation of these consensus motifs reduced SUMOylation of the protein. Unexpectedly, we observed that introducing these mutations into HAdV promotes adenoviral replication. In conclusion, we offer novel insights into adenovirus core proteins and provide evidence that SUMOylation of HAdV factors regulates replication efficiency. Copyright © 2018 American Society for Microbiology.

  14. Smokers making a quit attempt using e-cigarettes with or without nicotine or prescription nicotine replacement therapy: Impact on cardiovascular function (ISME-NRT - a study protocol

    Directory of Open Access Journals (Sweden)

    Markos Klonizakis

    2017-04-01

    Full Text Available Abstract Background The estimated number of cigarette smokers in the world is 1.3 billion, expected to rise to 1.7 billion by 2025, with 10 million smokers living in the U.K. Smoking is the leading, preventable death-cause worldwide, being responsible for almost 650,000 deaths in the E.U. annually. A combination of pharmacological interventions, including nicotine replacement therapy, bupropion and varenicline, and behavioural support is the most effective approach to smoking cessation. However, even the best methods have high relapse rates of approximately 75% within 6 months. Electronic (or “e-“ cigarettes use battery power to disperse a solution that usually contains propylene glycol or glycerine, water, flavouring and nicotine. E-cigarettes have become the most popular smoking cessation aid in England, however, information on their effects on cardiovascular function is limited and contradictory. As e-cigarettes are not solely nicotine-based products, existing research exploring the effects of nicotine on the cardio-vasculature provides only limited information, while their extensive uptake urges the need of evidence to inform the general public, smokers and policy-makers. Methods This is a pragmatic, 3-group, randomised, assessor-blinded, single-centre trial exploring the cardiovascular physiological effects of the use of e-cigarettes (nicotine-free and nicotine-inclusive, assessed separately combined with behavioural support as a smoking cessation method in comparison to the combination of NRT and behavioural support. The primary outcome will be macro-vascular function, determined by a Flow Mediated Dilatation ultrasound assessment, 6 months following participants’ “quit date”. Discussion Participants will be assessed at baseline, 3 days following their self-determined “quit date”, at intervention end (3 months and 6 months following their “quite date”. Findings are expected to give an indication of the cardiovascular

  15. Smokers making a quit attempt using e-cigarettes with or without nicotine or prescription nicotine replacement therapy: Impact on cardiovascular function (ISME-NRT) - a study protocol.

    Science.gov (United States)

    Klonizakis, Markos; Crank, Helen; Gumber, Anil; Brose, Leonie S

    2017-04-04

    The estimated number of cigarette smokers in the world is 1.3 billion, expected to rise to 1.7 billion by 2025, with 10 million smokers living in the U.K. Smoking is the leading, preventable death-cause worldwide, being responsible for almost 650,000 deaths in the E.U. annually. A combination of pharmacological interventions, including nicotine replacement therapy, bupropion and varenicline, and behavioural support is the most effective approach to smoking cessation. However, even the best methods have high relapse rates of approximately 75% within 6 months. Electronic (or "e-") cigarettes use battery power to disperse a solution that usually contains propylene glycol or glycerine, water, flavouring and nicotine. E-cigarettes have become the most popular smoking cessation aid in England, however, information on their effects on cardiovascular function is limited and contradictory. As e-cigarettes are not solely nicotine-based products, existing research exploring the effects of nicotine on the cardio-vasculature provides only limited information, while their extensive uptake urges the need of evidence to inform the general public, smokers and policy-makers. This is a pragmatic, 3-group, randomised, assessor-blinded, single-centre trial exploring the cardiovascular physiological effects of the use of e-cigarettes (nicotine-free and nicotine-inclusive, assessed separately) combined with behavioural support as a smoking cessation method in comparison to the combination of NRT and behavioural support. The primary outcome will be macro-vascular function, determined by a Flow Mediated Dilatation ultrasound assessment, 6 months following participants' "quit date". Participants will be assessed at baseline, 3 days following their self-determined "quit date", at intervention end (3 months) and 6 months following their "quite date". Findings are expected to give an indication of the cardiovascular effects of e-cigarettes both in the short- and in the medium-term period

  16. Acupuncture Decreases Blood Pressure Related to Hypothalamus Functional Connectivity with Frontal Lobe, Cerebellum, and Insula: A Study of Instantaneous and Short-Term Acupuncture Treatment in Essential Hypertension

    Directory of Open Access Journals (Sweden)

    Yu Zheng

    2016-01-01

    Full Text Available The therapeutic effects of acupuncture in decreasing blood pressure are ambiguous and underlying acupuncture in hypertension treatment has not been investigated. Our objective was to observe the change of quality of life and compare the differences in brain functional connectivity by investigating instantaneous and short-term acupuncture treatment in essential hypertension patients. A total of 30 patients were randomly divided into the LR3 group and sham acupoint group. Subjects received resting-state fMRI among preacupuncture, postinstantaneous, and short-term acupuncture treatment in two groups. Hypothalamus was selected as the seed point to analyze the changes in connectivity. We found three kinds of results: (1 There was statistical difference in systolic blood pressure in LR3 group after the short-term treatment and before acupuncture. (2 Compared with sham acupoint, acupuncture at LR3 instantaneous effects in the functional connectivity with seed points was more concentrated in the frontal lobe. (3 Compared with instantaneous effects, acupuncture LR3 short-term effects in the functional connectivity with seed points had more regions in frontal lobe, cerebellum, and insula. These brain areas constituted a neural network structure with specific functions that could explain the mechanism of therapy in hypertension patients by LR3 acupoint.

  17. Tracking Time-Varying Coefficient-Functions

    DEFF Research Database (Denmark)

    Nielsen, Henrik Aalborg; Nielsen, Torben Skov; Joensen, Alfred K.

    1999-01-01

    A conditional parametric ARX-model is an ARX-model in which the parameters re replaced by smooth functions of an, possibly multivariate, externalinput signal. These functions are called coefficient functions is suggested. Essentially, in its most simple form, this method is a combination of recur...

  18. Lipid Replacement Therapy Functional Food Formulation with NT Factor for Reducing Weight, Girth, Body Mass, Appetite and Fatigue While Improving Blood Lipid Profiles

    Directory of Open Access Journals (Sweden)

    Rita R. Ellithorpe

    2012-01-01

    Full Text Available Background: Lipid Replacement Therapy using NT Factor® plus kidney bean alpha-amylase inhibitor (Healthy Curb® was used in a two month weight loss clinical trial to reduce weight and improve fatigue without changing easting or exercise patterns and without use of drugs, stimulants or herbs. Objectives: To determine the effects of an all-natural functional food, NT Factor® plus alpha-amylase inhibitor (Healthy Curb®, on weight loss, body girth, body mass and index, basal metabolic rate, appetite, carvings for sweets and fatigue as well as blood lipid profiles during a 2-month open label clinical trial without food restrictions or increases in physical activity.Methods: Thirty subjects (Mean Age = 56.8 ± 1.8; 24 females and 6 males used the functional food containing NT Factor® (500 mg and alpha-amylase inhibitor (500 mg 30 min before each meal in tablet form. Participants were told to eat and exercise normally. Weight, waist and hip measurements were taken weekly. Appetite and sweet cravings were assessed weekly by standard methods. Fatigue was determined using the Piper Fatigue Scale. Blood samples were taken prior to and at the end of the trial for lipid and chemical analyses. Results: Sixty-three percent of the participants lost an average of 6.11 ± 0.28 pounds (2.77 ± 0.12 Kg (p<0.001 along with average reductions of 2.51 ± 0.05 inches (6.4 ± 0.13 cm (p<0.0001 and 1.5 ± 0.04 inches (3.8 ± 0.10 cm (p<0.0001 from waist and hip circumferences, respectively. The entire Functional Foods in Health and Disease 2012, 2(1:11-24 group lost an average of 3.63 ± 0.13 pounds (1.65 ± 0.11 Kg (p<0.001 with average reductions of 1.59 ± 0.03 inches (4.04 ± 0.06 cm (p<0.0001 and 1.13 ± 0.02 inch (2.87 ± 0.05 cm (p<0.0001 from waist and hip circumferences, respectively. Weight loss and body measurement decreases were gradual, consistent and significant, along with reductions in body mass index (BMI and basal metabolic rate (BMR measurements

  19. Oxidative phosphorylation is essential for felid sperm function, but is substantially lower in cheetah (Acinonyx jubatus) compared to domestic cat (Felis catus) ejaculate.

    Science.gov (United States)

    Terrell, Kimberly A; Wildt, David E; Anthony, Nicola M; Bavister, Barry D; Leibo, S P; Penfold, Linda M; Marker, Laurie L; Crosier, Adrienne E

    2011-09-01

    Compared with the normospermic domestic cat, sperm metabolic function is compromised in the teratospermic cat and cheetah, but the pathway(s) involved in this deficiency are unknown. Glycolysis is essential for sperm motility, yet it appears to function normally in spermatozoa of either species regardless of structural morphology. We conducted a comparative study to further understand the mechanisms of energy production in felid spermatozoa, with the hypothesis that oxidative phosphorylation is required for normal sperm function and is impaired in teratospermic ejaculates. Electroejaculates from both species were stained with MitoTracker to quantify mitochondrial membrane potential (MMP) or were incubated to assess changes in sperm function (motility, acrosomal integrity, and lactate production) after mitochondrial inhibition with myxothiazol. Sperm midpiece dimensions also were quantified. Sperm mitochondrial fluorescence (directly proportional to MMP) was ~95% lower in the cheetah compared with the normospermic and teratospermic cat, despite the cheetah having a 10% longer midpiece. In both species, MMP was increased 5-fold in spermatozoa with retained cytoplasm compared with structurally normal cells. Inhibition of oxidative phosphorylation impaired sperm function in both species, but a 100-fold higher inhibitor concentration was required in the cat compared with the cheetah. Collectively, findings revealed that oxidative phosphorylation was required for sperm function in the domestic cat and cheetah. This pathway of energy production appeared markedly less active in the cheetah, indicating a species-specific vulnerability to mitochondrial dysfunction. The unexpected, cross-species linkage between retained cytoplasmic droplets and elevated MMP may reflect increased concentrations of metabolic enzymes or substrates in these structures.

  20. Essential astrophysics

    CERN Document Server

    Lang, Kenneth R

    2013-01-01

    Essential Astrophysics is a book to learn or teach from, as well as a fundamental reference volume for anyone interested in astronomy and astrophysics. It presents astrophysics from basic principles without requiring any previous study of astronomy or astrophysics. It serves as a comprehensive introductory text, which takes the student through the field of astrophysics in lecture-sized chapters of basic physical principles applied to the cosmos. This one-semester overview will be enjoyed by undergraduate students with an interest in the physical sciences, such as astronomy, chemistry, engineering or physics, as well as by any curious student interested in learning about our celestial science. The mathematics required for understanding the text is on the level of simple algebra, for that is all that is needed to describe the fundamental principles. The text is of sufficient breadth and depth to prepare the interested student for more advanced specialized courses in the future. Astronomical examples are provide...

  1. Non-essential genes form the hubs of genome scale protein function and environmental gene expression networks in Salmonella enterica serovar Typhimurium

    DEFF Research Database (Denmark)

    Rosenkrantz, Jesper T.; Aarts, Henk; Abee, Tjakko

    2013-01-01

    Background: Salmonella Typhimurium is an important pathogen of human and animals. It shows a broad growth range and survives in harsh conditions. The aim of this study was to analyze transcriptional responses to a number of growth and stress conditions as well as the relationship of metabolic...... genes under a number of growth and stress conditions were used to construct a bipartite network connecting culture conditions and significantly regulated genes (transcriptional network). Also, a genome scale network was constructed for strain LT2. The latter connected genes with metabolic pathways...... pathways and/or cell functions at the genome-scale-level by network analysis, and further to explore whether highly connected genes ( hubs) in these networks were essential for growth, stress adaptation and virulence. Results: De novo generated as well as published transcriptional data for 425 selected...

  2. Essential ITIL processes and functions

    CERN Document Server

    , AXELOS

    2012-01-01

    A short introductory overview to ITIL and ITIL processes. It can be used as an entry point, giving insight into ITIL and guiding the reader to specific topics within the ITIL core guidance publications to help them find out more. It can also be used in its own right to provide basic information about the ITIL framework and its processes.

  3. The Essential Function for Serum Response Factor in T-Cell Development Reflects Its Specific Coupling to Extracellular Signal-Regulated Kinase Signaling ▿ †

    Science.gov (United States)

    Mylona, Anastasia; Nicolas, Robert; Maurice, Diane; Sargent, Mathew; Tuil, David; Daegelen, Dominique; Treisman, Richard; Costello, Patrick

    2011-01-01

    Serum response factor (SRF) recruits members of two families of signal-regulated coactivators, the extracellular signal-regulated kinase (ERK)-regulated ternary complex factors (TCFs) and the actin-regulated myocardin-related transcription factors (MRTFs), to its target genes through its DNA-binding domain. Whether coactivator association is required for SRF function in vivo and whether particular SRF functions reflect specific coupling to one or the other signal pathway have remained largely unexplored. We show that SRF is essential for thymocyte positive selection and thymic Treg and NK T-cell development but dispensable for early thymocyte development and negative selection. Expression of wild-type SRF, or mutants lacking the N-terminal phosphorylation sites or C-terminal transcriptional activation domain, restores positive selection in SRF null thymocytes. In contrast, SRF.V194E, which cannot recruit TCF or MRTF family members, is inactive, although it is recruited to target genes. Fusion of a TCF C-terminal activation domain to SRF.V194E effectively restores ERK-dependent single-positive (SP) thymocyte development. The resulting SP thymocytes exhibit normal surface marker expression and proliferation following T-cell receptor cross-linking. Thus, ERK signaling through the TCF pathway to SRF is necessary and sufficient for SRF function in thymocyte positive selection. PMID:21098124

  4. Multifunctional G-rich and RRM-containing domains of TbRGG2 perform separate yet essential functions in trypanosome RNA editing.

    Science.gov (United States)

    Foda, Bardees M; Downey, Kurtis M; Fisk, John C; Read, Laurie K

    2012-09-01

    Efficient editing of Trypanosoma brucei mitochondrial RNAs involves the actions of multiple accessory factors. T. brucei RGG2 (TbRGG2) is an essential protein crucial for initiation and 3'-to-5' progression of editing. TbRGG2 comprises an N-terminal G-rich region containing GWG and RG repeats and a C-terminal RNA recognition motif (RRM)-containing domain. Here, we perform in vitro and in vivo separation-of-function studies to interrogate the mechanism of TbRGG2 action in RNA editing. TbRGG2 preferentially binds preedited mRNA in vitro with high affinity attributable to its G-rich region. RNA-annealing and -melting activities are separable, carried out primarily by the G-rich and RRM domains, respectively. In vivo, the G-rich domain partially complements TbRGG2 knockdown, but the RRM domain is also required. Notably, TbRGG2's RNA-melting activity is dispensable for RNA editing in vivo. Interactions between TbRGG2 and MRB1 complex proteins are mediated by both G-rich and RRM-containing domains, depending on the binding partner. Overall, our results are consistent with a model in which the high-affinity RNA binding and RNA-annealing activities of the G-rich domain are essential for RNA editing in vivo. The RRM domain may have key functions involving interactions with the MRB1 complex and/or regulation of the activities of the G-rich domain.

  5. Replacing a Missing Tooth

    Science.gov (United States)

    ... there are two options for replacement: First, a removable partial denture may be used to replace the missing tooth. ... appearance look and feel more natural than a removable partial denture. However, it does require grinding down the support ...

  6. Ankle replacement - discharge

    Science.gov (United States)

    ... total - discharge; Total ankle arthroplasty - discharge; Endoprosthetic ankle replacement - discharge; Osteoarthritis - ankle ... You had an ankle replacement. Your surgeon removed and reshaped ... an artificial ankle joint. You received pain medicine and were ...

  7. Artificial Disc Replacement

    Science.gov (United States)

    ... Spondylolisthesis BLOG FIND A SPECIALIST Treatments Artificial Disc Replacement (ADR) Patient Education Committee Jamie Baisden The disc ... Disc An artificial disc (also called a disc replacement, disc prosthesis or spine arthroplasty device) is a ...

  8. Elbow replacement - discharge

    Science.gov (United States)

    Total elbow arthroplasty - discharge; Endoprosthetic elbow replacement - discharge ... Pain is normal after elbow replacement surgery. It should get better over time. Your doctor will give you a prescription for pain medicine. Get it filled when ...

  9. Partial knee replacement - slideshow

    Science.gov (United States)

    ... medlineplus.gov/ency/presentations/100225.htm Partial knee replacement - series—Normal anatomy To use the sharing features ... M. Editorial team. Related MedlinePlus Health Topics Knee Replacement A.D.A.M., Inc. is accredited by ...

  10. Hip joint replacement - slideshow

    Science.gov (United States)

    ... medlineplus.gov/ency/presentations/100006.htm Hip joint replacement - series—Normal anatomy To use the sharing features ... M. Editorial team. Related MedlinePlus Health Topics Hip Replacement A.D.A.M., Inc. is accredited by ...

  11. Kidney Replacement Therapy

    Science.gov (United States)

    ... Size: A A A Listen En Español Kidney Replacement Therapy Diabetes sometimes damages kidneys so badly that ... Dialysis Dialysis, the more common form of kidney-replacement therapy, is a way of cleaning the blood ...

  12. Knee joint replacement - slideshow

    Science.gov (United States)

    ... medlineplus.gov/ency/presentations/100088.htm Knee joint replacement - series—Normal anatomy To use the sharing features ... M. Editorial team. Related MedlinePlus Health Topics Knee Replacement A.D.A.M., Inc. is accredited by ...

  13. Hip replacement - precautions

    Science.gov (United States)

    ... page, please enable JavaScript. After you have hip replacement surgery, you will need to be careful how ... to Expect at Home After you have hip replacement surgery, you will need to be careful how ...

  14. Hip replacement - discharge

    Science.gov (United States)

    ... discharge; Total hip replacement - discharge; Hip hemiarthroplasty - discharge; Osteoarthritis - hip replacement discharge ... such as downhill skiing or contact sports like football and soccer. But you should be able to ...

  15. Non-essential genes form the hubs of genome scale protein function and environmental gene expression networks in Salmonella enterica serovar Typhimurium.

    Science.gov (United States)

    Rosenkrantz, Jesper T; Aarts, Henk; Abee, Tjakko; Rolfe, Matthew D; Knudsen, Gitte M; Nielsen, Maj-Britt; Thomsen, Line E; Zwietering, Marcel H; Olsen, John E; Pin, Carmen

    2013-12-17

    Salmonella Typhimurium is an important pathogen of human and animals. It shows a broad growth range and survives in harsh conditions. The aim of this study was to analyze transcriptional responses to a number of growth and stress conditions as well as the relationship of metabolic pathways and/or cell functions at the genome-scale-level by network analysis, and further to explore whether highly connected genes (hubs) in these networks were essential for growth, stress adaptation and virulence. De novo generated as well as published transcriptional data for 425 selected genes under a number of growth and stress conditions were used to construct a bipartite network connecting culture conditions and significantly regulated genes (transcriptional network). Also, a genome scale network was constructed for strain LT2. The latter connected genes with metabolic pathways and cellular functions. Both networks were shown to belong to the family of scale-free networks characterized by the presence of highly connected nodes or hubs which are genes whose transcription is regulated when responding to many of the assayed culture conditions or genes encoding products involved in a high number of metabolic pathways and cell functions.The five genes with most connections in the transcriptional network (wraB, ygaU, uspA, cbpA and osmC) and in the genome scale network (ychN, siiF (STM4262), yajD, ybeB and dcoC) were selected for mutations, however mutagenesis of ygaU and ybeB proved unsuccessful. No difference between mutants and the wild type strain was observed during growth at unfavorable temperatures, pH values, NaCl concentrations and in the presence of H2O2. Eight mutants were evaluated for virulence in C57/BL6 mice and none differed from the wild type strain. Notably, however, deviations of phenotypes with respect to the wild type were observed when combinations of these genes were deleted. Network analysis revealed the presence of hubs in both transcriptional and functional

  16. Capital Equipment Replacement Decisions

    OpenAIRE

    Batterham, Robert L.; Fraser, K.I.

    1995-01-01

    This paper reviews the literature on the optimal replacement of capital equipment, especially farm machinery. It also considers the influence of taxation and capital rationing on replacement decisions. It concludes that special taxation provisions such as accelerated depreciation and investment allowances are unlikely to greatly influence farmers' capital equipment replacement decisions in Australia.

  17. Receptor complementation and mutagenesis reveal SR-BI as an essential HCV entry factor and functionally imply its intra- and extra-cellular domains.

    Directory of Open Access Journals (Sweden)

    Marlène Dreux

    2009-02-01

    Full Text Available HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI, a major receptor of high-density lipoprotein (HDL, the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection.

  18. Dental ontogeny and replacement in Pliosauridae.

    Science.gov (United States)

    Sassoon, Judyth; Foffa, Davide; Marek, Ryan

    2015-11-01

    Dental morphology and patterns of tooth replacement in representatives of the clade Pliosauridae (Reptilia, Sauropterygia) are evaluated in detail. The jaws of one basal (Thalassiodracon hawkinsii) and two derived species (Pliosaurus carpenteri, Pliosaurus kevani) were visualized by μCT scans, and the ontogenetic patterns, or 'movement paths', of replacement teeth could be mapped. Other specimens (Peloneustes philarchus and Pliosaurus westbuyensis) with well-preserved jaws containing functional and replacement teeth in situ were also examined directly, and waves of tooth replacement could be inferred from the degree of in situ tooth development and the fusion between functional and replacement alveoli. The analysis revealed symmetrical tooth eruption over the medial axis throughout the length of the jaw in the basal pliosaurid Thalassiodracon. By contrast, symmetrical tooth eruption patterns occur only along the anterior sections of the jaws of derived pliosaurids. In Pliosaurus, replacement schedules differ in the anterior and posterior portions of the jaws and appear to correlate with differences in tooth morphology and symmetrical replacement. The anterior teeth exhibit longer replacement cycle periods and symmetrical replacement, while shorter cycle periods and asymmetry are seen posteriorly. A longer period suggests slower replacement and is characteristic of large, specialized caniniform teeth in the longer snouted Late Jurassic taxa. Smaller posterior teeth have a shorter period and therefore a faster replacement cycle. The transition from long to short replacement period over the length of the jaw is thought to account for the loss of symmetry. This differentiation could relate to differential tooth function and a type of heterodonty. We therefore propose a new model of pliosaurid tooth replacement patterns and present it in a phylogenetic context.

  19. Replacement of Poly(vinyl pyrrolidone) by Thiols: A Systematic Study of Ag Nanocube Functionalization by Surface-Enhanced Raman Scattering

    OpenAIRE

    Moran, Christine H.; Rycenga, Matthew; Zhang, Qiang; Xia, Younan

    2011-01-01

    In this work, we used surface-enhanced Raman scattering (SERS) to monitor the replacement of poly(vinyl pyrrolidone) (PVP) on Ag nanocubes by cysteamine, thiol-terminated PEG, and benzenedithiol. PVP is widely used as a colloidal stabilizer and capping agent to control the shape of Ag (as well as many other noble metals) nanocrystals during synthesis, and to stabilize the final colloidal suspension. However, the surface chemistry of Ag nanocrystals often needs to be tailored for specific appl...

  20. Replacement of Poly(vinyl pyrrolidone) by Thiols: A Systematic Study of Ag Nanocube Functionalization by Surface-Enhanced Raman Scattering.

    Science.gov (United States)

    Moran, Christine H; Rycenga, Matthew; Zhang, Qiang; Xia, Younan

    2011-11-10

    In this work, we used surface-enhanced Raman scattering (SERS) to monitor the replacement of poly(vinyl pyrrolidone) (PVP) on Ag nanocubes by cysteamine, thiol-terminated PEG, and benzenedithiol. PVP is widely used as a colloidal stabilizer and capping agent to control the shape of Ag (as well as many other noble metals) nanocrystals during synthesis, and to stabilize the final colloidal suspension. However, the surface chemistry of Ag nanocrystals often needs to be tailored for specific applications, so the PVP coating must be removed and/or replaced by other ligands. By monitoring the signature peak from the carbonyl groups of PVP, we show, for the first time, that the PVP adsorbed on the surface of Ag nanocubes was completely replaced by the thiol molecules at room temperature over the course of a few hours. We observed the same trend no matter if the Ag nanocubes were suspended in an aqueous solution of the thiol or supported on a silicon substrate and then immersed in the thiol solution.

  1. Optimal replacement policy for safety-related multi-component multi-state systems

    International Nuclear Information System (INIS)

    Xu Ming; Chen Tao; Yang Xianhui

    2012-01-01

    This paper investigates replacement scheduling for non-repairable safety-related systems (SRS) with multiple components and states. The aim is to determine the cost-minimizing time for replacing SRS while meeting the required safety. Traditionally, such scheduling decisions are made without considering the interaction between the SRS and the production system under protection, the interaction being essential to formulate the expected cost to be minimized. In this paper, the SRS is represented by a non-homogeneous continuous time Markov model, and its state distribution is evaluated with the aid of the universal generating function. Moreover, a structure function of SRS with recursive property is developed to evaluate the state distribution efficiently. These methods form the basis to derive an explicit expression of the expected system cost per unit time, and to determine the optimal time to replace the SRS. The proposed methodology is demonstrated through an illustrative example.

  2. Essentials of anterior cruciate ligament rupture management.

    Science.gov (United States)

    Klinge, Stephen A; Sawyer, Gregory A; Hulstyn, Michael J

    2013-05-01

    Anterior cruciate ligament (ACL) rupture is a common knee injury and an understanding of current medical knowledge regarding its management is essential. Accurate and prompt diagnosis requires an awareness of injury mechanisms and risk factors, common symptoms and physical/radiologic findings. Early mobilization and physical therapy improves outcomes regardless of treatment modality. Many older patients regain sufficient stability and function after non-operative rehabilitation. Early ACL reconstruction is appropriate for younger patients and those who engage in activities requiring frequent pivoting and rapid direction changes. ACL surgery involves reconstruction of the torn ligament tissue with various replacement graft options, each with advantages and disadvantages. The guidance of a knowledgeable and experienced therapist is required throughout an intensive and prolonged rehabilitation course. Generally excellent outcomes and low complication rates are expected, but treatment does not prevent late osteoarthritis.

  3. Content and chemical composition of Hyptis marrubioides essential oil in function of seasons - doi: 10.4025/actasciagron.v32i3.3415

    OpenAIRE

    Botrel, Priscila Pereira; UFLA; Pinto, José Eduardo Brasil Pereira; UFLA; Ferraz, Vany; UFMG; Bertolucci, Suzan Kelly Vilela; UFLA; Figueiredo, Felipe Campos; Campus-Pesquisa

    2010-01-01

    Essential oils are odorous principles stored in special plant cells. The essential oil in the Hyptis genus is traditionally used as an anesthetic, antispasmodic, anti-inflammatory, and can induce abortion in high doses. The purpose of this work was to evaluate the influence of seasons in essential oil content and chemical composition of species H. marrubioides. A completely randomized complete design was used with four treatments (winter, spring, summer and autumn) and six replications, tota...

  4. Arabidopsis lipocalins AtCHL and AtTIL have distinct but overlapping functions essential for lipid protection and seed longevity.

    Science.gov (United States)

    Boca, Simona; Koestler, Fleur; Ksas, Brigitte; Chevalier, Anne; Leymarie, Juliette; Fekete, Agnes; Mueller, Martin J; Havaux, Michel

    2014-02-01

    Lipocalins are a group of multifunctional proteins, recognized as carriers of small lipophilic molecules, which have been characterized in bacteria and animals. Two true lipocalins have been recently identified in plants, the temperature-induced lipocalin (TIL) and the chloroplastic lipocalin (CHL), the expression of which is induced by various abiotic stresses. Each lipocalin appeared to be specialized in the responses to specific stress conditions in Arabidopsis thaliana, with AtTIL and AtCHL playing a protective role against heat and high light, respectively. The double mutant AtCHL KO × AtTIL KO deficient in both lipocalins was more sensitive to temperature, drought and light stresses than the single mutants, exhibiting intense lipid peroxidation. AtCHL deficiency dramatically enhanced the photosensitivity of mutants (vte1, npq1) affected in lipid protection mechanisms (tocopherols, zeaxanthin), confirming the role of lipocalins in the prevention of lipid peroxidation. Seeds of the AtCHL KO × AtTIL KO double mutant were very sensitive to natural and artificial ageing, and again this phenomenon was associated with the oxidation of polyunsaturated lipids. The presented results show that the Arabidopsis lipocalins AtTIL and AtCHL have overlapping functions in lipid protection which are essential for stress resistance and survival. © 2013 John Wiley & Sons Ltd.

  5. T-bet expression by Foxp3+ T regulatory cells is not essential for their suppressive function in CNS autoimmune disease or colitis

    Directory of Open Access Journals (Sweden)

    Rhoanne C McPherson

    2015-02-01

    Full Text Available Accumulation of T regulatory (Treg cells within the central nervous system (CNS during experimental autoimmune encephalomyelitis (EAE is essential for the resolution of disease. CNS Treg cells have been shown to uniformly express the Th1-associated molecules T-bet and CXCR3. Here we report that the expression of T-bet is not required for the function of these Treg within the CNS. Using mice that lacked T-bet expression specifically within the Treg compartment, we demonstrate that there was no deficit in Treg recruitment into the CNS during EAE and no difference in the resolution of disease compared to control mice. T-bet deficiency did not impact on the in vitro suppressive capacity of Treg. Transfer of T-bet-deficient Treg was able to suppress clinical signs of either EAE, or colitis. These observations demonstrate that, although Treg can acquire characteristics associated with pathogenic Teff cells, this process is not necessarily required for their suppressive capacity and the resolution of autoimmune inflammation.

  6. HuD and the Survival Motor Neuron Protein Interact in Motoneurons and Are Essential for Motoneuron Development, Function, and mRNA Regulation.

    Science.gov (United States)

    Hao le, Thi; Duy, Phan Q; An, Min; Talbot, Jared; Iyer, Chitra C; Wolman, Marc; Beattie, Christine E

    2017-11-29

    Motoneurons establish a critical link between the CNS and muscles. If motoneurons do not develop correctly, they cannot form the required connections, resulting in movement defects or paralysis. Compromised development can also lead to degeneration because the motoneuron is not set up to function properly. Little is known, however, regarding the mechanisms that control vertebrate motoneuron development, particularly the later stages of axon branch and dendrite formation. The motoneuron disease spinal muscular atrophy (SMA) is caused by low levels of the survival motor neuron (SMN) protein leading to defects in vertebrate motoneuron development and synapse formation. Here we show using zebrafish as a model system that SMN interacts with the RNA binding protein (RBP) HuD in motoneurons in vivo during formation of axonal branches and dendrites. To determine the function of HuD in motoneurons, we generated zebrafish HuD mutants and found that they exhibited decreased motor axon branches, dramatically fewer dendrites, and movement defects. These same phenotypes are present in animals expressing low levels of SMN, indicating that both proteins function in motoneuron development. HuD binds and transports mRNAs and one of its target mRNAs, Gap43 , is involved in axonal outgrowth. We found that Gap43 was decreased in both HuD and SMN mutants. Importantly, transgenic expression of HuD in motoneurons of SMN mutants rescued the motoneuron defects, the movement defects, and Gap43 mRNA levels. These data support that the interaction between SMN and HuD is critical for motoneuron development and point to a role for RBPs in SMA. SIGNIFICANCE STATEMENT In zebrafish models of the motoneuron disease spinal muscular atrophy (SMA), motor axons fail to form the normal extent of axonal branches and dendrites leading to decreased motor function. SMA is caused by low levels of the survival motor neuron (SMN) protein. We show in motoneurons in vivo that SMN interacts with the RNA binding

  7. Pretherapeutic Functional Imaging Allows Prediction of Head Tremor Arrest After Thalamotomy for Essential Tremor: The Role of Altered Interconnectivity Between Thalamolimbic and Supplementary Motor Circuits.

    Science.gov (United States)

    Tuleasca, Constantin; Régis, Jean; Najdenovska, Elena; Witjas, Tatiana; Girard, Nadine; Champoudry, Jérôme; Faouzi, Mohamed; Thiran, Jean-Philippe; Cuadra, Meritxell Bach; Levivier, Marc; Van De Ville, Dimitri

    2018-04-01

    To correlate pretherapeutic resting-state functional magnetic resonance imaging (rs-fMRI) measures with pretherapeutic head tremor presence and/or further improvement 1 year after stereotactic radiosurgical thalamotomy (SRS-T) for essential tremor (ET). We prospectively collected head tremor scores (range, 0-3) and rs-fMRI data for a cohort of 17 consecutive ET patients in pretherapeutic and 1 year after SRS-T states. We additionally acquired rs-fMRI data for a healthy control (HC) group (n = 12). Group-level independent component analysis (n = 17 for pretherapeutic rs-fMRI) was applied to decompose neuroimaging data into 20 large-scale brain networks using a standard approach. Through spatial regression, we projected 1 year after SRS-T and HC rs-fMRI time points, on the same 20 brain networks. Pretherapeutic interconnectivity (IC) strength between the network including bilateral thalamus and limbic system with left supplementary motor area predicted head tremor improvement at 1 year after SRS-T (family-wise corrected P < 0.001, cluster size K c  = 146). For the statistically significant cluster, IC strength was strongest in HCs (mean, 4.6; median, 3.8) compared with pre- (mean, 0.1; median, 0.2) or posttherapeutic (mean, -0.2; median, 0.09) states. Baseline measures of IC between bilateral thalamus and limbic system with left supplementary motor area may predict head tremor arrest after thalamotomy. However, procedures such as SRS-T, for this particular clinical feature, do not align patients to HCs in terms of functional brain connectivity. We postulate that supplementary motor area is modulating head tremor appearance, by abnormal connectivity with the thalamolimbic system. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. The Arginine/Lysine-Rich Element within the DNA-Binding Domain Is Essential for Nuclear Localization and Function of the Intracellular Pathogen Resistance 1.

    Science.gov (United States)

    Yao, Kezhen; Wu, Yongyan; Chen, Qi; Zhang, Zihan; Chen, Xin; Zhang, Yong

    2016-01-01

    The mouse intracellular pathogen resistance 1 (Ipr1) gene plays important roles in mediating host immunity and previous work showed that it enhances macrophage apoptosis upon mycobacterium infection. However, to date, little is known about the regulation pattern of Ipr1 action. Recent studies have investigated the protein-coding genes and microRNAs regulated by Ipr1 in mouse macrophages, but the structure and the functional motif of the Ipr1 protein have yet to be explored. In this study, we analyzed the domains and functional motif of the Ipr1 protein. The resulting data reveal that Ipr1 protein forms a homodimer and that the Sp100-like domain mediates the targeting of Ipr1 protein to nuclear dots (NDs). Moreover, we found that an Ipr1 mutant lacking the classic nuclear localization signal (cNLS) also translocated into the nuclei, suggesting that the cNLS is not the only factor that directs Ipr1 nuclear localization. Additionally, mechanistic studies revealed that an arginine/lysine-rich element within the DNA-binding domain (SAND domain) is critical for Ipr1 binding to the importin protein receptor NPI-1, demonstrating that this element plays an essential role in mediating the nuclear localization of Ipr1 protein. Furthermore, our results show that this arginine/lysine-rich element contributes to the transcriptional regulation and apoptotic activity of Ipr1. These findings highlight the structural foundations of Ipr1 action and provide new insights into the mechanism of Ipr1-mediated resistance to mycobacterium.

  9. Identification and characterization of a novel serine protease, VvpS, that contains two functional domains and is essential for autolysis of Vibrio vulnificus.

    Science.gov (United States)

    Lim, Moon Sub; Kim, Jeong-A; Lim, Jong Gyu; Kim, Byoung Sik; Jeong, Kwang Cheol; Lee, Kyu-Ho; Choi, Sang Ho

    2011-08-01

    Little is known about the molecular mechanism for autolysis of Gram-negative bacteria. In the present study, we identified the vvpS gene encoding a serine protease, VvpS, from Vibrio vulnificus, a Gram-negative food-borne pathogen. The amino acid sequence predicted that VvpS consists of two functional domains, an N-terminal protease catalytic domain (PCD) and a C-terminal carbohydrate binding domain (CBD). A null mutation of vvpS significantly enhanced viability during stationary phase, as measured by enumerating CFU and differentially staining viable cells. The vvpS mutant reduced the release of cytoplasmic β-galactosidase and high-molecular-weight extracellular chromosomal DNA into the culture supernatants, indicating that VvpS contributes to the autolysis of V. vulnificus during stationary phase. VvpS is secreted via a type II secretion system (T2SS), and it exerts its effects on autolysis through intracellular accumulation during stationary phase. Consistent with this, a disruption of the T2SS accelerated intracellular accumulation of VvpS and thereby the autolysis of V. vulnificus. VvpS also showed peptidoglycan-hydrolyzing activity, indicating that the autolysis of V. vulnificus is attributed to the self-digestion of the cell wall by VvpS. The functions of the VvpS domains were assessed by C-terminal deletion analysis and demonstrated that the PCD indeed possesses a proteolytic activity and that the CBD is required for hydrolyzing peptidoglycan effectively. Finally, the vvpS mutant exhibited reduced virulence in the infection of mice. In conclusion, VvpS is a serine protease with a modular structure and plays an essential role in the autolysis and pathogenesis of V. vulnificus.

  10. Identification and Characterization of a Novel Serine Protease, VvpS, That Contains Two Functional Domains and Is Essential for Autolysis of Vibrio vulnificus ▿

    Science.gov (United States)

    Lim, Moon Sub; Kim, Jeong-A; Lim, Jong Gyu; Kim, Byoung Sik; Jeong, Kwang Cheol; Lee, Kyu-Ho; Choi, Sang Ho

    2011-01-01

    Little is known about the molecular mechanism for autolysis of Gram-negative bacteria. In the present study, we identified the vvpS gene encoding a serine protease, VvpS, from Vibrio vulnificus, a Gram-negative food-borne pathogen. The amino acid sequence predicted that VvpS consists of two functional domains, an N-terminal protease catalytic domain (PCD) and a C-terminal carbohydrate binding domain (CBD). A null mutation of vvpS significantly enhanced viability during stationary phase, as measured by enumerating CFU and differentially staining viable cells. The vvpS mutant reduced the release of cytoplasmic β-galactosidase and high-molecular-weight extracellular chromosomal DNA into the culture supernatants, indicating that VvpS contributes to the autolysis of V. vulnificus during stationary phase. VvpS is secreted via a type II secretion system (T2SS), and it exerts its effects on autolysis through intracellular accumulation during stationary phase. Consistent with this, a disruption of the T2SS accelerated intracellular accumulation of VvpS and thereby the autolysis of V. vulnificus. VvpS also showed peptidoglycan-hydrolyzing activity, indicating that the autolysis of V. vulnificus is attributed to the self-digestion of the cell wall by VvpS. The functions of the VvpS domains were assessed by C-terminal deletion analysis and demonstrated that the PCD indeed possesses a proteolytic activity and that the CBD is required for hydrolyzing peptidoglycan effectively. Finally, the vvpS mutant exhibited reduced virulence in the infection of mice. In conclusion, VvpS is a serine protease with a modular structure and plays an essential role in the autolysis and pathogenesis of V. vulnificus. PMID:21642466

  11. Inhaled essential oil from Chamaecyparis obtuse ameliorates the impairments of cognitive function induced by injection of β-amyloid in rats.

    Science.gov (United States)

    Bae, Donghyuck; Seol, Heejin; Yoon, Ho-Geun; Na, Ju-Ryun; Oh, Kyonyeo; Choi, Chul Yung; Lee, Dong-wook; Jun, Woojin; Youl Lee, Kwang; Lee, Jeongmin; Hwang, Kwontack; Lee, Yoo-Hyun; Kim, Sunoh

    2012-07-01

    Chamaecyparis obtusa Sieb. & Zucc., Endlicher (Cupressaceae) forest bathing or aromatherapy has been shown in various studies to have biological functions such as anticancer, antiallergies, antiinflammatory, and antioxidant activity. However, no reports exist on the pharmacological or biological activities of the essential oil of C. obtusa (EOCO) or its effects on central nervous system. The aggregation and formation of β-amyloid peptides (Aβ) into fibrils are central events in the pathogenesis of Alzheimer's disease (AD), and overproduction and aggregation of Aβ into oligomers have been known to trigger neurotoxicity. In this study, we investigated the effects of inhaled EOCO on cognitive function and neuronal apoptosis in rats intrahippocampally injected with Aβ. To model AD, 4 μg of aggregated Aβ was injected into the hippocampus. To test the effects of EOCO, behavioral performance in the Morris water maze was tested 4 days after injection. After behavioral testing, brain sections were prepared for TTC staining and TUNEL assay. Inhaled EOCO protected spatial learning and memory from the impairments induced by Aβ(1-40) injection. In addition, the behavioral deficits accompanying Aβ(1-40)-induced AD were attenuated by inhalation of EOCO. Furthermore, acetylcholinesterase (AChE) activity and neuronal apoptosis were significantly inhibited in rats treated with Aβ(1-40) and EOCO compared to rats treated only with Aβ(1-40). EOCO suppressed both AD-related neuronal cell apoptosis and AD-related dysfunction of the memory system. Thus, the results of this study support EOCO as a candidate drug for the treatment of AD.

  12. Prioritization methodology for chemical replacement

    Science.gov (United States)

    Cruit, Wendy; Goldberg, Ben; Schutzenhofer, Scott

    1995-01-01

    Since United States of America federal legislation has required ozone depleting chemicals (class 1 & 2) to be banned from production, The National Aeronautics and Space Administration (NASA) and industry have been required to find other chemicals and methods to replace these target chemicals. This project was initiated as a development of a prioritization methodology suitable for assessing and ranking existing processes for replacement 'urgency.' The methodology was produced in the form of a workbook (NASA Technical Paper 3421). The final workbook contains two tools, one for evaluation and one for prioritization. The two tools are interconnected in that they were developed from one central theme - chemical replacement due to imposed laws and regulations. This workbook provides matrices, detailed explanations of how to use them, and a detailed methodology for prioritization of replacement technology. The main objective is to provide a GUIDELINE to help direct the research for replacement technology. The approach for prioritization called for a system which would result in a numerical rating for the chemicals and processes being assessed. A Quality Function Deployment (QFD) technique was used in order to determine numerical values which would correspond to the concerns raised and their respective importance to the process. This workbook defines the approach and the application of the QFD matrix. This technique: (1) provides a standard database for technology that can be easily reviewed, and (2) provides a standard format for information when requesting resources for further research for chemical replacement technology. Originally, this workbook was to be used for Class 1 and Class 2 chemicals, but it was specifically designed to be flexible enough to be used for any chemical used in a process (if the chemical and/or process needs to be replaced). The methodology consists of comparison matrices (and the smaller comparison components) which allow replacement technology

  13. Aeronautical Information System Replacement -

    Data.gov (United States)

    Department of Transportation — Aeronautical Information System Replacement is a web-enabled, automation means for the collection and distribution of Service B messages, weather information, flight...

  14. Options for Heart Valve Replacement

    Science.gov (United States)

    ... are the most commonly replaced valves. Pulmonary and tricuspid valve replacements are fairly uncommon in adults. Replacing a ... Problems and Causes • Risks, Signs and Symptoms • Accurate Diagnosis • Treatment Options ... Repair Valve Replacement - Ross Procedure - Newer Surgery Options - ...

  15. IPv6 Essentials

    CERN Document Server

    Hagen, Silvia

    2006-01-01

    IPv6 Essentials, Second Edition provides a succinct, in-depth tour of all the new features and functions in IPv6. It guides you through everything you need to know to get started, including how to configure IPv6 on hosts and routers and which applications currently support IPv6. Aimed at system and network administrators, engineers, network designers, and IT managers, this book will help you understand, plan for, design, and integrate IPv6 into your current IPv4 infrastructure

  16. Radiation Source Replacement Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, Jeffrey W.; Moran, Traci L.; Bond, Leonard J.

    2010-12-01

    This report summarizes a Radiation Source Replacement Workshop in Houston Texas on October 27-28, 2010, which provided a forum for industry and researchers to exchange information and to discuss the issues relating to replacement of AmBe, and potentially other isotope sources used in well logging.

  17. Effects of 3-week total meal replacement vs. typical food-based diet on human brain functional magnetic resonance imaging food-cue reactivity and functional connectivity in people with obesity.

    Science.gov (United States)

    Kahathuduwa, Chanaka Nadeeshan; Davis, Tyler; O'Boyle, Michael; Boyd, Lori Ann; Chin, Shao-Hua; Paniukov, Dmitrii; Binks, Martin

    2018-01-01

    Calorie restriction via total meal replacement (TMR) results in greater reduction of food cravings compared to reduced-calorie typical diet (TD). Direct evidence of the impact of these interventions on human brain fMRI food-cue reactivity (fMRI-FCR) and functional connectivity is absent. We examined the effects of a 3-week 1120 kcal/d TMR intervention as compared to an iso-caloric TD intervention using an fMRI-FCR paradigm. Thirty-two male and female subjects with obesity (19-60 years; 30-39.9 kg/m 2 ) participated in a randomized two-group repeated measures dietary intervention study consisting of 1120 kcal/d from either 1) TMR (shakes), 2) TD (portion control). Pre-intervention and following the 3-week diet fMRI-FCR, functional connectivity, food cravings (Food Craving Inventory) and weight were considered. Compared to TD, TMR showed increased fMRI-FCR of the bilateral dorsolateral prefrontal (dlPFC), orbitofrontal, anterior cingulate, primary motor and left insular cortices and bilateral nucleus accumbens regions in the post-intervention state relative to the pre-intervention state. Compared to TD, TMR was also associated with negative modulation of fMRI-FCR of the nucleus accumbens, orbitofrontal cortex and amygdala by dlPFC. Reduced body weight (4.87 kg, P < 0.001), body fat (2.19 kg, P = 0.004) and overall food cravings (0.41, P = 0.047) were seen in the TMR group. In the TD group reduced body weight (2.37 kg, P = 0.004) and body fat (1.64 kg, P = 0.002) were noted. Weight loss was significantly greater in TMR versus TD (2.50 kg, P = 0.007). Greater weight loss and reduced cravings, coupled with stronger activations and potential negative modulation of the food reward related regions by the dlPFC during exposure to visual food cues is consistent with increased executive control in TMR vs. TD. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. The role of pain and functional impairment in the decision to recommend total joint replacement in hip and knee osteoarthritis: an international cross-sectional study of 1909 patients. Report of the OARSI-OMERACT Task Force on total joint replacement

    DEFF Research Database (Denmark)

    Gossec, L; Paternotte, S; Maillefert, J F

    2011-01-01

    : In all, 1909 patients were included (1130 knee/779 hip OA). Mean age was 66.4 [standard deviation (SD) 10.9] years, 58.1% were women; 628/1130 (55.6%) knee OA and 574/779 (73.7%) hip OA patients were recommended for TJR. Although patients recommended for TJR (yes vs no) had worse symptom levels [pain, 55......OBJECTIVE: To assess the pain and functional disability levels corresponding to an indication for total joint replacement (TJR) in hip and knee osteoarthritis (OA). METHODS: Design: International cross-sectional study in 10 countries. Patients: Consecutive outpatients with definite hip or knee OA...... attending an orthopaedic outpatient clinic. Gold standard measure for recommendation for TJR: Surgeon's decision that TJR is justified. Outcome measures: Pain (ICOAP: intermittent and constant osteoarthritis pain, 0-100) and functional impairment (HOOS-PS/KOOS-PS: Hip/Knee injury and Osteoarthritis Outcome...

  19. Long-term enzyme replacement therapy is associated with reduced proteinuria and preserved proximal tubular function in women with Fabry disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Birn, Henrik; Bibby, Bo M

    2014-01-01

    BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficiency of α-galactosidase A (α-Gal A) causes intracellular accumulations of globotriaosylceramide (GL-3) and related glycosphingolipids in all organs, including the kidney, often leading...... to end-stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant α-Gal A reduces cellular GL-3 deposits in podocytes...... dysfunction in women with Fabry disease treated with ERT. METHODS: A retrospective, single centre, cohort study evaluated the long-term association between ERT, albuminuria and eGFR in 13 women with Fabry disease and mild renal involvement. In particular, we analysed the changes in the proteinuric profile...

  20. A comparison of psychological functioning in couples undergoing frozen-thawed embryo replacement in various stages of treatment using the Mean Affect Adjective Check List (MAACL).

    Science.gov (United States)

    Ismail, W A; Menezes, M Q; Martin, C W; Thong, K J

    2004-09-01

    The objectives were to identify the stage(s) of frozen embryo replacement cycle where the couples are most vulnerable to psychological dysfunction. Assessment was performed by using the Mean Affect Adjective Check-List (MAACL). Thirty couples completed the MAACL questionnaire at the following stages: (a) pretreatment (visit 1), (b) before embryo transfer (visit 2), and (c) before pregnancy test (visit 3). Each partner had to complete a separate questionnaire set. For both partners, the depression score for visit 3 was significantly higher and the sensation seeking and positive affect scores were significantly lower than the corresponding scores for earlier visits. Anxiety scores were similar for all visits. For men, the hostility scores were significantly higher between visits 1 and 2 while in women the same was reported between visits 3 and 2. Psychological counselling should be targeted at couples especially after embryo transfer. MAACL is a useful method for measuring psychological dysfunction in these couples.

  1. Calcium, essential for health

    Science.gov (United States)

    Martínez de Victoria, Emilio

    2016-07-12

    Calcium (Ca) is the most abundant mineral element in our body. It accounts for about 2% of body weight. The functions of calcium are: a) functions skeletal and b) regulatory functions. Bone consists of a protein matrix that mineralizes mainly with calcium (the most abundant), phosphate and magnesium, for it is essential an adequate dietary intake of Ca, phosphorus and vitamin D. The ionic Ca (Ca2+) is essential to maintain and / or perform different specialized functions of, virtually, all body cells cellular. Because of its important functions Ca2+ must be closely regulated, keeping plasma concentrations within narrow ranges. For this reason there is an accurate response against hypocalcemia or hypercalcemia in which the parathormone, calcitriol, calcitonin and vitamin K are involved. Ca intakes in the Spanish population are low in a significant percentage of the older adult’s population, especially in women. The main source of Ca in the diet is milk and milk derivatives. Green leafy vegetables, fruits and legumes can be important sources of Ca in a Mediterranean dietary pattern. The bioavailability of dietary Ca depends on physiological and dietary factors. Physiological include age, physiological status (gestation and lactation) Ca and vitamin D status and disease. Several studies relate Ca intake in the diet and various diseases, such as osteoporosis, cancer, cardiovascular disease and obesity.

  2. An assessment of the impact of behavioural cognitions on function in patients partaking in a trial of early home-based progressive resistance training after total hip replacement surgery.

    Science.gov (United States)

    Okoro, T; Morrison, V; Maddison, P; Lemmey, A B; Andrew, J G

    2013-01-01

    Control cognitions have been directly related to positive engagement with rehabilitation regimes. The impact of such cognitions on recovery following surgery is not well understood. To assess whether perceived control cognitions predict function 9-12 months following total hip replacement (THR). Prospective cohort study performed as part of a randomised controlled trial. Behavioural cognitions (BC) (recovery locus of control (RLOC); perceived external behavioural control (PEBC))) and subjective functional outcome measures (Oxford hip score (OHS) and a reduced version of the Western Ontario and McMasters University Osteoarthritis Function scale (rWOMAC PF)) were administered pre-operatively and up to 12 months post-operatively to 50 patients randomised to home-based progressive resistance training (N = 26) or standard rehabilitation (N = 24), post-THR. Regression analysis investigated variance in functional scores. Group randomisation had no effect on BC. RLOC and OHS (6 months) correlated significantly with 12-month OHS, with 6-month OHS predicting 62.3% of the variance in 12-month OHS. 12-month rWOMAC PF was determined by each of its three previous assessments (pre-operative 8.8%, 6 weeks 17.8% and 6 months 67.3%). Variance in functional gain at 12 months (OHS and rWOMAC PF) was explained by pre-operative OHS and rWOMAC PF (63.7% and 63.8%, respectively). BC had no impact on functional outcome in this population. Subjectively assessed function at 12 months, as well as the levels of functional gain over time, was best explained by the patients' earlier functional status. Implications for Rehabilitation It is important to assess psychological factors such as poor pre-operative mental health and pain catastrophising in patients undergoing joint replacement surgery as these factors have an adverse effect on subjective patient outcomes. Pre-operative behavioural cognitions appear to have no impact on subjective functional outcome at 12 months post-THR. The pre

  3. Replacement of the JRR-3 computer system

    International Nuclear Information System (INIS)

    Kato, Tomoaki; Kobayashi, Kenichi; Suwa, Masayuki; Mineshima, Hiromi; Sato, Mitsugu

    2000-01-01

    The JRR-3 computer system contributes to stable operation of JRR-3 since 1990. But now about 10 years have passed since it was designed and some problems have occurred. Under these situations, we should replace the old computer system for safe and stable operation. In this replacement, the system is improved as regards man-machine interface and efficiency about maintenance. The new system consists of three functions, which are 'the function of management for operation information' (renewal function), 'the function of management for facility information' (new function) and the function of management for information publication' (new function). By this replacement, New JRR-3 computer system can contribute to safe and stable operation. (author)

  4. d-myo-Inositol-3-Phosphate Affects Phosphatidylinositol-Mediated Endomembrane Function in Arabidopsis and Is Essential for Auxin-Regulated Embryogenesis[W][OA

    Science.gov (United States)

    Luo, Yu; Qin, Genji; Zhang, Jun; Liang, Yuan; Song, Yingqi; Zhao, Meiping; Tsuge, Tomohiko; Aoyama, Takashi; Liu, Jingjing; Gu, Hongya; Qu, Li-Jia

    2011-01-01

    In animal cells, myo-inositol is an important regulatory molecule in several physiological and biochemical processes, including signal transduction and membrane biogenesis. However, the fundamental biological functions of myo-inositol are still far from clear in plants. Here, we report the genetic characterization of three Arabidopsis thaliana genes encoding d-myo-inositol-3-phosphate synthase (MIPS), which catalyzes the rate-limiting step in de novo synthesis of myo-inositol. Each of the three MIPS genes rescued the yeast ino1 mutant, which is defective in yeast MIPS gene INO1, and they had different dynamic expression patterns during Arabidopsis embryo development. Although single mips mutants showed no obvious phenotypes, the mips1 mips2 double mutant and the mips1 mips2 mips3 triple mutant were embryo lethal, whereas the mips1 mips3 and mips1 mips2+/− double mutants had abnormal embryos. The mips phenotypes resembled those of auxin mutants. Indeed, the double and triple mips mutants displayed abnormal expression patterns of DR5:green fluorescent protein, an auxin-responsive fusion protein, and they had altered PIN1 subcellular localization. Also, membrane trafficking was affected in mips1 mips3. Interestingly, overexpression of PHOSPHATIDYLINOSITOL SYNTHASE2, which converts myo-inositol to membrane phosphatidylinositol (PtdIns), largely rescued the cotyledon and endomembrane defects in mips1 mips3. We conclude that myo-inositol serves as the main substrate for synthesizing PtdIns and phosphatidylinositides, which are essential for endomembrane structure and trafficking and thus for auxin-regulated embryogenesis. PMID:21505066

  5. 17β-Estradiol-induced interaction of estrogen receptor α and human atrial essential myosin light chain modulates cardiac contractile function.

    Science.gov (United States)

    Duft, Karolin; Schanz, Miriam; Pham, Hang; Abdelwahab, Ahmed; Schriever, Cindy; Kararigas, Georgios; Dworatzek, Elke; Davidson, Mercy M; Regitz-Zagrosek, Vera; Morano, Ingo; Mahmoodzadeh, Shokoufeh

    2017-01-01

    Chronic increased workload of the human heart causes ventricular hypertrophy, re-expression of the atrial essential myosin light chain (hALC-1), and improved contractile function. Although hALC-1 is an important positive inotropic regulator of the human heart, little is known about its regulation. Therefore, we investigated the role of the sex hormone 17β-estradiol (E2) on hALC-1 gene expression, the underlying molecular mechanisms, and the impact of this regulatory process on cardiac contractile function. We showed that E2 attenuated hALC-1 expression in human atrial tissues of both sexes and in human ventricular AC16 cells. E2 induced the nuclear translocation of estrogen receptor alpha (ERα) and hALC-1 in AC16 cells, where they cooperatively regulate the transcriptional activity of hALC-1 gene promoter. E2-activated ERα required the estrogen response element (ERE) motif within the hALC-1 gene promoter to reduce its transcriptional activity (vehicle: 15.55 ± 4.80 vs. E2: 6.51 ± 3.69; ~2 fold). This inhibitory effect was potentiated in the presence of hALC-1 (vehicle: 11.13 ± 3.66 vs. E2: 2.18 ± 1.10; ~5 fold), and thus, hALC-1 acts as a co-repressor of ERα-mediated transcription. Yeast two-hybrid screening of a human heart cDNA library revealed that ERα interacts physically with hALC-1 in the presence of E2. This interaction was confirmed by Co-Immunoprecipitation and immunofluorescence in human atrium. As a further novel effect, we showed that chronic E2-treatment of adult mouse cardiomyocytes overexpressing hALC-1 resulted in reduced cell-shortening amplitude and twitching kinetics of these cells independent of Ca 2+ activation levels. Together, our data showed that the expression of hALC-1 gene is, at least partly, regulated by E2/ERα, while hALC-1 acts as a co-repressor. The inotropic effect of hALC-1 overexpression in cardiomyocytes can be significantly repressed by E2.

  6. Human Health Safety Evaluation of Halon Replacement Candidates

    National Research Council Canada - National Science Library

    Dodd, D. E; Jepson, G. W; Macko, Jr, J. A

    2000-01-01

    .... The services within the Department of Defense (DoD) are directed to determine and evaluate suitable halon replacement candidates that will optimize performance of mission-essential equipment and operations...

  7. Could wind replace nuclear?

    International Nuclear Information System (INIS)

    2017-01-01

    This article aims at assessing the situation produced by a total replacement of nuclear energy by wind energy, while facing consumption demand at any moment, notably in December. The authors indicate the evolution of the French energy mix during December 2016, and the evolution of the rate between wind energy production and the sum of nuclear and wind energy production during the same month, and then give briefly some elements regarding necessary investments in wind energy to wholly replace nuclear energy. According to them, such a replacement would be ruinous

  8. Age replacement models: A summary with new perspectives and methods

    International Nuclear Information System (INIS)

    Zhao, Xufeng; Al-Khalifa, Khalifa N.; Magid Hamouda, Abdel; Nakagawa, Toshio

    2017-01-01

    Age replacement models are fundamental to maintenance theory. This paper summarizes our new perspectives and hods in age replacement models: First, we optimize the expected cost rate for a required availability level and vice versa. Second, an asymptotic model with simple calculation is proposed by using the cumulative hazard function skillfully. Third, we challenge the established theory such that preventive replacement should be non-random and only corrective replacement should be made for the unit with exponential failure. Fourth, three replacement policies with random working cycles are discussed, which are called overtime replacement, replacement first, and replacement last, respectively. Fifth, the policies of replacement first and last are formulated with general models. Sixth, age replacement is modified for the situation when the economical life cycle of the unit is a random variable with probability distribution. Finally, models of a parallel system with constant and random number of units are taken into considerations. The models of expected cost rates are obtained and optimal replacement times to minimize them are discussed analytically and computed numerically. Further studies and potential applications are also indicated at the end of discussions of the above models. - Highlights: • Optimization of cost rate for availability level is discussed and vice versa. • Asymptotic and random replacement models are discussed. • Overtime replacement, replacement first and replacement last are surveyed. • Replacement policy with random life cycle is given. • A parallel system with random number of units is modeled.

  9. An abstract machine model of dynamic module replacement

    OpenAIRE

    Walton, Chris; Kırlı, Dilsun; Gilmore, Stephen

    2000-01-01

    In this paper we define an abstract machine model for the mλ typed intermediate language. This abstract machine is used to give a formal description of the operation of run-time module replacement for the programming language Dynamic ML. The essential technical device which we employ for module replacement is a modification of two-space copying garbage collection. We show how the operation of module replacement could be applied to other garbage-collected languages such as Java.

  10. Speckle tracking echocardiography derived 2-dimensional myocardial strain predicts left ventricular function and mass regression in aortic stenosis patients undergoing aortic valve replacement.

    Science.gov (United States)

    Staron, Adam; Bansal, Manish; Kalakoti, Piyush; Nakabo, Ayumi; Gasior, Zbigniew; Pysz, Piotr; Wita, Krystian; Jasinski, Marek; Sengupta, Partho P

    2013-04-01

    Regression of left ventricular (LV) mass in severe aortic stenosis (AS) following aortic valve replacement (AVR) reduces the potential risk of sudden death and congestive heart failure associated with LV hypertrophy. We investigated whether abnormalities of resting LV deformation in severe AS can predict the lack of regression of LV mass following AVR. Two-dimensional speckle tracking echocardiography (STE) was performed in a total of 100 subjects including 60 consecutive patients with severe AS having normal LV ejection fraction (EF > 50 %) and 40 controls. STE was performed preoperatively and at 4 months following AVR, including longitudinal strain assessed from the apical 4-chamber and 2-chamber views and the circumferential and rotational mechanics measured from the apical short axis view. In comparison with controls, the patients with AS showed a significantly lower LV longitudinal (p regression (>10 %) following AVR. In conclusion, STE can quantify the burden of myocardial dysfunction in patients with severe AS despite the presence of normal LV ejection fraction. Furthermore, resting abnormalities in circumferential strain at LV apex is related with a hemodynamic milieu associated with the lack of LV mass regression during short-term follow up after AVR.

  11. Partial knee replacement

    Science.gov (United States)

    ... candidate for partial knee replacement and what the success rate is for your condition. Alternative Names Unicompartmental ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  12. Tool Inventory and Replacement

    Science.gov (United States)

    Bear, W. Forrest

    1976-01-01

    Vocational agriculture teachers are encouraged to evaluate curriculum offerings, the new trends in business and industry, and develop a master tool purchase and replacement plan over a 3- to 5-year period. (HD)

  13. Slab replacement maturity guidelines.

    Science.gov (United States)

    2014-04-01

    This study investigated the use of maturity method to determine early age strength of concrete in slab : replacement application. Specific objectives were (1) to evaluate effects of various factors on the compressive : maturity-strength relationship ...

  14. The replacement research reactor

    International Nuclear Information System (INIS)

    Cameron, R.

    1999-01-01

    As a consequences of the government decision in September 1997. ANSTO established a replacement research reactor project to manage the procurement of the replacement reactor through the necessary approval, tendering and contract management stages This paper provides an update of the status of the project including the completion of the Environmental Impact Statement. Prequalification and Public Works Committee processes. The aims of the project, management organisation, reactor type and expected capabilities are also described

  15. Antenna Controller Replacement Software

    Science.gov (United States)

    Chao, Roger Y.; Morgan, Scott C.; Strain, Martha M.; Rockwell, Stephen T.; Shimizu, Kenneth J.; Tehrani, Barzia J.; Kwok, Jaclyn H.; Tuazon-Wong, Michelle; Valtier, Henry; Nalbandi, Reza; hide

    2010-01-01

    The Antenna Controller Replacement (ACR) software accurately points and monitors the Deep Space Network (DSN) 70-m and 34-m high-efficiency (HEF) ground-based antennas that are used to track primarily spacecraft and, periodically, celestial targets. To track a spacecraft, or other targets, the antenna must be accurately pointed at the spacecraft, which can be very far away with very weak signals. ACR s conical scanning capability collects the signal in a circular pattern around the target, calculates the location of the strongest signal, and adjusts the antenna pointing to point directly at the spacecraft. A real-time, closed-loop servo control algorithm performed every 0.02 second allows accurate positioning of the antenna in order to track these distant spacecraft. Additionally, this advanced servo control algorithm provides better antenna pointing performance in windy conditions. The ACR software provides high-level commands that provide a very easy user interface for the DSN operator. The operator only needs to enter two commands to start the antenna and subreflector, and Master Equatorial tracking. The most accurate antenna pointing is accomplished by aligning the antenna to the Master Equatorial, which because of its small size and sheltered location, has the most stable pointing. The antenna has hundreds of digital and analog monitor points. The ACR software provides compact displays to summarize the status of the antenna, subreflector, and the Master Equatorial. The ACR software has two major functions. First, it performs all of the steps required to accurately point the antenna (and subreflector and Master Equatorial) at the spacecraft (or celestial target). This involves controlling the antenna/ subreflector/Master-Equatorial hardware, initiating and monitoring the correct sequence of operations, calculating the position of the spacecraft relative to the antenna, executing the real-time servo control algorithm to maintain the correct position, and

  16. Physical interaction and functional coupling between ACDP4 and the intracellular ion chaperone COX11, an implication of the role of ACDP4 in essential metal ion transport and homeostasis

    Directory of Open Access Journals (Sweden)

    Gu Jianguo

    2005-04-01

    Full Text Available Abstract Divalent metal ions such as copper, manganese, and cobalt are essential for cell development, differentiation, function and survival. These essential metal ions are delivered into intracellular domains as cofactors for enzymes involved in neuropeptide and neurotransmitter synthesis, superoxide metabolism, and other biological functions in a target specific fashion. Altering the homeostasis of these essential metal ions is known to connect to a number of human diseases including Alzheimer disease, amyotrophic lateral sclerosis, and pain. It remains unclear how these essential metal ions are delivered to intracellular targets in mammalian cells. Here we report that rat spinal cord dorsal horn neurons express ACDP4, a member of Ancient Conserved Domain Protein family. By screening a pretransformed human fetal brain cDNA library in a yeast two-hybrid system, we have identified that ACDP4 specifically interacts with COX11, an intracellular metal ion chaperone. Ectopic expression of ACDP4 in HEK293 cells resulted in enhanced toxicity to metal ions including copper, manganese, and cobalt. The metal ion toxicity became more pronounced when ACDP4 and COX11 were co-expressed ectopically in HEK293 cells, suggesting a functional coupling between them. Our results indicate a role of ACDP4 in metal ion homeostasis and toxicity. This is the first report revealing a functional aspect of this ancient conserved domain protein family. We propose that ACDP is a family of transporter protein or chaperone proteins for delivering essential metal ions in different mammalian tissues. The expression of ACDP4 on spinal cord dorsal horn neurons may have implications in sensory neuron functions under physiological and pathological conditions.

  17. Effects of partial replacement of dietary starch from barley or corn with lactose on ruminal function, short-chain fatty acid absorption, nitrogen utilization, and production performance of dairy cows.

    Science.gov (United States)

    Chibisa, G E; Gorka, P; Penner, G B; Berthiaume, R; Mutsvangwa, T

    2015-04-01

    In cows fed diets based on corn-alfalfa silage, replacing starch with sugar improves milk production. Although the rate of ruminal fermentation of sugar is more rapid than that of starch, evidence has been found that feeding sugar as a partial replacement for starch does not negatively affect ruminal pH despite increasing diet fermentability. The mechanism(s) for this desirable response are unknown. Our objective was to determine the effects of replacing barley or corn starch with lactose (as dried whey permeate; DWP) on ruminal function, short-chain fatty acid (SCFA) absorption, and nitrogen (N) utilization in dairy cows. Eight lactating cows were used in a replicated 4 × 4 Latin square design with 28-d periods and source of starch (barley vs. corn) and level of DWP (0 vs. 6%, DM basis) as treatment factors. Four cows in 1 Latin square were ruminally cannulated for the measurement of ruminal function, SCFA absorption, and N utilization. Dry matter intake and milk and milk component yields did not differ with diet. The dietary addition of DWP tended to increase ruminal butyrate concentration (13.6 vs. 12.2 mmol/L), and increased the Cl(-)-competitive absorption rates for acetate and propionate. There was no sugar effect on minimum ruminal pH, and the duration and area when ruminal pH was below 5.8. Minimum ruminal pH tended to be lower in cows fed barley compared with those fed corn (5.47 vs. 5.61). The duration when ruminal pH was below pH 5.8 tended to be shorter (186 vs. 235 min/d), whereas the area (pH × min/d) that pH was below 5.8 was smaller (47 vs. 111) on the corn than barley diets. Cows fed the high- compared with the low-sugar diet had lower ruminal NH3-N concentration. Feeding the high-sugar diet tended to increase apparent total-tract digestibility of dry matter and organic matters and increased apparent total-tract digestibility of fat. Apparent total-tract digestibility of N tended to be greater in cows fed barley compared with those fed corn

  18. Linker 2 of the eukaryotic pre-ribosomal processing factor Mrd1p is an essential interdomain functionally coupled to upstream RNA Binding Domain 2 (RBD2)

    OpenAIRE

    Lackmann, Fredrik; Belikov, Sergey; Wieslander, Lars

    2017-01-01

    Ribosome synthesis is an essential process in all cells. In Sacharomyces cerevisiae, the precursor rRNA, 35S pre-rRNA, is folded and assembled into a 90S pre-ribosomal complex. The 40S ribosomal subunit is processed from the pre-ribosomal complex. This requires concerted action of small nucleolar RNAs, such as U3 snoRNA, and a large number of trans-acting factors. Mrd1p, one of the essential small ribosomal subunit synthesis factors is required for cleavage of the 35S pre-rRNA to generate 18S...

  19. MooTools essentials

    CERN Document Server

    Newton, Aaron

    2008-01-01

    Mootools is a light, modular JavaScript framework that makes adding Ajax, animations, and interactive elements to your site a breeze. But it's more than fancy effects and shortcuts; Mootools enhances the JavaScript language and makes writing clean, object oriented code almost pleasant. Unlocking the power of Mootools, and therefore JavaScript, isn't that hard, but knowing where to start can be. Mootools Essentials aims to help you accomplish that task with the following: * Illustrations of nearly every class and function in the library * Real world examples of how to use them * Written by Moot

  20. Arteriovenous renal replacement therapy in end-stage left-sided heart failure patients has a detrimental effect on patients with impaired right ventricular function.

    Science.gov (United States)

    Repasos, Evangelos; Kaldara, Elisabeth; Pantsios, Christos; Kapelios, Chris; Nana, Emmeleia; Vernadakis, Spiridon; Melexopoulou, Christina; Malliaras, Konstantinos; Boletis, John; Nanas, John N

    Chronic intermittent renal replacement therapy(RRT) is an alternate method of decongestion for patients presenting with diuretic-resistant, end-stage heart failure(HF) and cardiorenal syndrome. The optimal method of vascular access has not been confirmed. This study investigated the 6-month outcomes of patients with end-stage HF after the creation of arteriovenous communications (AVC) compared with other means of RRT. We treated 40 patients with chronic, intermittent, ambulatory RRT, of whom 15 (37.5%; Group A) underwent creation of AVC, and 25 (62.5%; Group B) received intraperitoneal (n=6) or internal jugular catheters (n=19) with the goal of achieving body weight stabilization and relief from congestion. The characteristics of the two groups were similar. According to Cox regression analysis, the 6-month rate of death or re-hospitalization for HF was significantly higher in Group A (73%) than in Group B (44%); hazard ratio (HR): 2.58; 95% confidence interval (CI) 1.2-6.2; P=0.02. Over a 6-month follow-up, the cumulative survival was significantly shorter (P=0.03) in Group A (13.8±10 weeks) than in Group B (20.7±7 weeks). In the 15 patients who received AVC, the only independent predictor of adverse outcome at 6 months was serum total bilirubin concentration (HR 2.5; 95% CI 1.1-5.7, p=0.02), whereas in the 25 patients who underwent other means of RRT, pulmonary vascular resistance (PVR) was identified as a risk factor for hospitalization or death at 1-year follow-up (HR 1.26; 95% CI 1.1-1.57, p=0.04). In patients with end-stage HF, the creation of AVC for intermittent RRT was followed by a significant increase in morbidity and mortality in comparison to the safe and effective placement of permanent central venous catheters. Patients with elevated PVR seem to comprise a group at high risk for adverse outcomes after central catheter insertion. Copyright © 2016 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.

  1. The influence of preoperative determinants on quality of life, functioning and pain after total knee and hip replacement: a pooled analysis of Dutch cohorts.

    Science.gov (United States)

    Hofstede, Stefanie N; Gademan, Maaike G J; Stijnen, Theo; Nelissen, Rob G H H; Marang-van de Mheen, Perla J

    2018-03-02

    Previous research has identified preoperative determinants that predict health related quality of life (HRQoL), functioning and pain after total knee or hip arthroplasty (TKA/THA), but these differed between studies and had opposite directions. This may be due to lack of power and not adjusting for confounders. The present study aims to identify the preoperative determinants that influence health related quality of life (HRQoL), functioning and pain after total knee or hip arthroplasty (TKA/THA). We pooled individual patient from 20 cohorts with OA patients data (n = 1783 TKA and n = 2400 THA) in the Netherlands. We examined the influence of age, gender, BMI and preoperative values of HRQoL, functioning and pain on postoperative status and total improvement. Linear mixed models were used to estimate the effect of each preoperative variable on a particular outcome for each cohort separately. These effects were pooled across cohorts using a random effects model. For each increase in preoperative point in HRQoL, the postoperative HRQoL increased by 0.51 points in TKA and 0.37 points in THA (SF-36 scale). Similarly, each point increase in preoperative functioning, resulted in a higher postoperative functioning of 0.31 (TKA) and 0.21 (THA) points (KOOS/HOOS-ADL scale). For pain this was 0.18 (TKA) and 0.15 (THA) points higher (KOOS/HOOS-pain scale) (higher means less pain). Even though patients with better preoperative values achieved better postoperative outcomes, their improvement was smaller. Women and patients with a higher BMI had more pain after a TKA and THA. Higher age and higher BMI was associated with lower postoperative HRQoL and functioning and more pain after a THA. Patients with a better preoperative health status have better outcomes, but less improvement. Even though the independent effects may seem small, combined results of preoperative variables may result in larger effects on postoperative outcomes.

  2. Xenopus Xp54 and human RCK/p54 helicases functionally replace yeast Dhh1p in brome mosaic virus RNA replication.

    Science.gov (United States)

    Alves-Rodrigues, Isabel; Mas, Antonio; Díez, Juana

    2007-04-01

    By using a Brome mosaic virus (BMV)-Saccharomyces cerevisiae system, we previously showed that the cellular Lsm1p-7p/Pat1p/Dhh1p decapping-activator complex functions in BMV RNA translation and replication. As a first approach in investigating whether the corresponding human homologues play a similar role, we expressed human Lsm1p (hLsm1p) and RCK/p54 in yeast. Expression of RCK/p54 but not hLsm1p restored the defect in BMV RNA translation and replication observed in the dhh1Delta and lsm1Delta strains, respectively. This functional conservation, together with the common replication strategies of positive-stranded RNA viruses, suggests that RCK/p54 may also play a role in the replication of positive-stranded RNA viruses that infect humans.

  3. Functional Feed Assessment on Litopenaeus vannamei Using 100% Fish Meal Replacement by Soybean Meal, High Levels of Complex Carbohydrates and Bacillus Probiotic Strains

    Directory of Open Access Journals (Sweden)

    Rosalia Contreras

    2011-06-01

    Full Text Available Functional feed supplemented with alternative-economic nutrient sources (protein, carbohydrates, lipids and probiotics are being considered in shrimp/fish aquaculture production systems as an option to increase yield and profits and to reduce water pollution. In this study the probiotic potential to formulate functional feeds have been evaluated using four dietary treatments: Treatment 1 (B + Bs; Bacillus subtilis potential probiotic strain was supplemented to a soybeanmeal (SBM—carbohydrates (CHO basal feed. Treatment 2 (B + Bm; Bacillus megaterium potential probiotic strain was supplemented to the same SBM-CHO basal feed. In Treatment 3 (B; SBM-CHO basal feed was not supplemented with probiotic strains. Treatment 4 (C; fishmeal commercial feed (FM was utilized as positive control. Feeding trials evaluated the survival, growth, and food conversion ratio and stress tolerance of juvenile Litopenaeus vannamei (Boone Pacific white shrimp. Best overall shrimp performance was observed for animals fed with Treatment 1 (B+Bs; additionally, stress tolerance and hemolymph metabolites also showed the best performance in this treatment. SBM-CHO basal feed not supplemented with probiotic strains (B presented smaller growth and lower feed conversion ratio (FCR. Shrimps fed with the fishmeal commercial feed (C presented the lowest stress tolerance to high ammonia and low oxygen levels. Specifically selected B. subtilis strains are recommended to formulate functional and economical feeds containing high levels of vegetable; protein and carbohydrates as main dietary sources in L. vannamei cultures.

  4. Functional feed assessment on Litopenaeus vannamei using 100% fish meal replacement by soybean meal, high levels of complex carbohydrates and Bacillus probiotic strains.

    Science.gov (United States)

    Olmos, Jorge; Ochoa, Leonel; Paniagua-Michel, Jesus; Contreras, Rosalia

    2011-01-01

    Functional feed supplemented with alternative-economic nutrient sources (protein, carbohydrates, lipids) and probiotics are being considered in shrimp/fish aquaculture production systems as an option to increase yield and profits and to reduce water pollution. In this study the probiotic potential to formulate functional feeds have been evaluated using four dietary treatments: Treatment 1 (B + Bs); Bacillus subtilis potential probiotic strain was supplemented to a soybeanmeal (SBM)-carbohydrates (CHO) basal feed. Treatment 2 (B + Bm); Bacillus megaterium potential probiotic strain was supplemented to the same SBM-CHO basal feed. In Treatment 3 (B); SBM-CHO basal feed was not supplemented with probiotic strains. Treatment 4 (C); fishmeal commercial feed (FM) was utilized as positive control. Feeding trials evaluated the survival, growth, and food conversion ratio and stress tolerance of juvenile Litopenaeus vannamei (Boone) Pacific white shrimp. Best overall shrimp performance was observed for animals fed with Treatment 1 (B+Bs); additionally, stress tolerance and hemolymph metabolites also showed the best performance in this treatment. SBM-CHO basal feed not supplemented with probiotic strains (B) presented smaller growth and lower feed conversion ratio (FCR). Shrimps fed with the fishmeal commercial feed (C) presented the lowest stress tolerance to high ammonia and low oxygen levels. Specifically selected B. subtilis strains are recommended to formulate functional and economical feeds containing high levels of vegetable; protein and carbohydrates as main dietary sources in L. vannamei cultures.

  5. The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement.

    Directory of Open Access Journals (Sweden)

    Filomena Monica Cavaliere

    Full Text Available The lack of BTK in X-linked agammaglobulinemia (XLA patients does not affect monocytes and polymorphonuclear cells (PMN phenotype and functions. In this study, we show that XLA patients had an increased frequency of the intermediate monocytes subset and that BTK-deficient monocytes and PMN had a normal expression of receptors involved in the activation and cellular responses. We demonstrate that BTK is not required for migration, phagocytosis and the production of reactive oxygen species (ROS following engagement of FC gamma receptors (FcγR. XLA monocytes and PMN showed an efficient calcium (Ca2+-independent activation of oxidative burst, suggesting that oxidative burst is less dependent by Ca2+ mobilization. The phagocytosis was functional and it remained unaltered also after Ca2+ chelation, confirming the independence of phagocytosis on Ca2+ mobilization. Intravenous immunoglobulin (IVIg infusion exerted an anti-inflammatory effect by reducing the frequency of pro-inflammatory monocytes. In monocytes, the IVIg reduce the oxidative burst and phagocytosis even if these functions remained efficient.

  6. The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement.

    Science.gov (United States)

    Cavaliere, Filomena Monica; Prezzo, Alessandro; Bilotta, Caterina; Iacobini, Metello; Quinti, Isabella

    2017-01-01

    The lack of BTK in X-linked agammaglobulinemia (XLA) patients does not affect monocytes and polymorphonuclear cells (PMN) phenotype and functions. In this study, we show that XLA patients had an increased frequency of the intermediate monocytes subset and that BTK-deficient monocytes and PMN had a normal expression of receptors involved in the activation and cellular responses. We demonstrate that BTK is not required for migration, phagocytosis and the production of reactive oxygen species (ROS) following engagement of FC gamma receptors (FcγR). XLA monocytes and PMN showed an efficient calcium (Ca2+)-independent activation of oxidative burst, suggesting that oxidative burst is less dependent by Ca2+ mobilization. The phagocytosis was functional and it remained unaltered also after Ca2+ chelation, confirming the independence of phagocytosis on Ca2+ mobilization. Intravenous immunoglobulin (IVIg) infusion exerted an anti-inflammatory effect by reducing the frequency of pro-inflammatory monocytes. In monocytes, the IVIg reduce the oxidative burst and phagocytosis even if these functions remained efficient.

  7. BWR control blade replacement strategies

    International Nuclear Information System (INIS)

    Kennard, M.W.; Harbottle, J.E.

    2000-01-01

    The reactivity control elements in a BWR, the control blades, perform three significant functions: provide shutdown margin during normal and accident operating conditions; provide overall core reactivity control; and provide axial power shaping control. As such, the blades are exposed to the core's neutron flux, resulting in irradiation of blade structural and absorber materials. Since the absorber depletes with time (if B 4 C is used, it also swells) and the structural components undergo various degradation mechanisms (e.g., embrittlement, corrosion), the blades have limits on their operational lifetimes. Consequently, BWR utilities have implemented strategies that aim to maximize blade lifetimes while balancing operational costs, such as extending a refuelling outage to shuffle high exposure blades. This paper examines the blade replacement strategies used by BWR utilities operating in US, Europe and Asia by assembling information related to: the utility's specific blade replacement strategy; the impact the newer blade designs and changes in core operating mode were having on those strategies; the mechanical and nuclear limits that determined those strategies; the methods employed to ensure that lifetime limits were not exceeded during operation; and blade designs used (current and replacement blades). (author)

  8. The caudal septum replacement graft.

    Science.gov (United States)

    Foda, Hossam M T

    2008-01-01

    To describe a technique for reconstructing the lost tip support in cases involving caudal septal and premaxillary deficiencies. The study included 120 patients with aesthetic and functional nasal problems resulting from the loss of caudal septal and premaxillary support. An external rhinoplasty approach was performed to reconstruct the lost support using a cartilaginous caudal septum replacement graft and premaxillary augmentation with Mersilene mesh. The majority of cases (75%) involved revisions in patients who had previously undergone 1 or more nasal surgical procedures. A caudal septum replacement graft was combined with premaxillary augmentation in 93 patients (77.5%). The mean follow-up period was 3 years (range, 1-12 years). The technique succeeded in correcting the external nasal deformities in all patients and resulted in a significant improvement in breathing in 74 patients (86%) with preoperative nasal obstruction. There were no cases of infection, displacement, or extrusion. The caudal septum replacement graft proved to be very effective in restoring the lost tip support in patients with caudal septal deficiency. Combining the graft with premaxillary augmentation using Mersilene mesh helped increase support and stability over long-term follow-up.

  9. Equipment Replacement Decision Making: Opportunities and Challenges

    OpenAIRE

    Fan, Wei (David); Gemar, Mason D.; Machemehl, Randy

    2012-01-01

    The primary function of equipment managers is to replace the right equipment at the right time and at the lowest overall cost. In this paper, the opportunities and challenges associated with equipment replacement optimization (ERO) are discussed in detail. First, a comprehensive review of the state-of-the art and state-of-the practice literature for the ERO problem is conducted. Second, a dynamic programming (DP) based optimization solution methodology is presented to solve the ERO problem. T...

  10. Product Platform Replacements

    DEFF Research Database (Denmark)

    Sköld, Martin; Karlsson, Christer

    2012-01-01

    . To shed light on this unexplored and growing managerial concern, the purpose of this explorative study is to identify operational challenges to management when product platforms are replaced. Design/methodology/approach – The study uses a longitudinal field-study approach. Two companies, Gamma and Omega......Purpose – It is argued in this article that too little is known about product platforms and how to deal with them from a manager's point of view. Specifically, little information exists regarding when old established platforms are replaced by new generations in R&D and production environments...... distinguishing between platform replacement “height” and “width”. Seven groups of managerial measures for dealing with the issues are recommended. Originality/value – The study aims to contribute to the existing literature by taking a managers' perspective of product platform development. Its specific...

  11. [Advances in targeted replacement genome editing in plants].

    Science.gov (United States)

    Wang, Honglin; Zhang, Congsheng; Liu, Changlin; Xie, Chuanxiao

    2017-10-25

    Targeted replacement genome editing refers to DNA modification and engineering technology that could induce and achieve mutations of targeted gene replacement or knockin at a target gene or DNA region. In this review, the principles, implementation methods, factors that influence efficiency and accuracy, and applications of gene replacement editing were summarized and discussed. It provides the reference for gene functional characterization and genetic improvements through gene replacement strategies in higher plant especially crops.

  12. Nickel-Catalyzed C–O Bond-Cleaving Alkylation of Esters: Direct Replacement of the Ester Moiety by Functionalized Alkyl Chains

    KAUST Repository

    Liu, Xiangqian

    2017-06-07

    Two efficient protocols for the nickel-catalyzed aryl–alkyl cross-coupling reactions using esters as coupling components have been established. The methods enable the selective oxidative addition of nickel to acyl C–O and aryl C–O bonds and allow the aryl–alkyl cross-coupling via decarbonylative bond cleavage or through cleavage of a C–O bond with high efficiency and good functional group compatibility. The protocols allow the streamlined, unconventional utilization of widespread ester groups and their precursors, carboxylic acids and phenols, in synthetic organic chemistry.

  13. Cervical intervertebral disc replacement.

    Science.gov (United States)

    Cason, Garrick W; Herkowitz, Harry N

    2013-02-06

    Symptomatic adjacent-level disease after cervical fusion has led to the development and testing of several disc-replacement prostheses. Randomized controlled trials of cervical disc replacement (CDR) compared with anterior cervical discectomy and fusion (ACDF) have demonstrated at least equivalent clinical results for CDR with similar or lower complication rates. Biomechanical, kinematic, and radiographic studies of CDR reveal that the surgical level and adjacent vertebral level motion and center of rotation more closely mimic the native state. Lower intradiscal pressures adjacent to CDR may help decrease the incidence of adjacent spinal-level disease, but long-term follow-up is necessary to evaluate this theory.

  14. Percutaneous pulmonary valve replacement using completely tissue-engineered off-the-shelf heart valves: six-month in vivo functionality and matrix remodelling in sheep.

    Science.gov (United States)

    Schmitt, Boris; Spriestersbach, Hendrik; O H-Icí, Darach; Radtke, Torben; Bartosch, Marco; Peters, Heiner; Sigler, Matthias; Frese, Laura; Dijkman, Petra E; Baaijens, Frank P T; Hoerstrup, Simon P; Berger, Felix

    2016-05-17

    The objective was to implant a stented decellularised tissue-engineered heart valve (sdTEHV) percutaneously in an animal model, to assess its in vivo functionality and to examine the repopulation and remodelling of the valvular matrix by the recipient's autologous cells. Prototypes of sdTEHV were cultured in vitro, decellularised and percutaneously implanted into the pulmonary position in 15 sheep. Functionality was assessed monthly by intracardiac echocardiography (ICE). Valves were explanted after eight, 16 or 24 weeks and analysed macroscopically, histologically and by electron microscopy. Implantation was successful in all animals. Valves showed normal pressure gradients throughout the study. Due to a suboptimal design with small coaptation area, stent ovality led to immediate regurgitation which continuously increased during follow-up. Analyses revealed complete endothelialisation and rapid cellular repopulation and remodelling of the entire matrix. Valves were free from endocarditis, calcification and graft rejection. sdTEHV can be safely implanted percutaneously. The fast autologous recellularisation and the extensive matrix remodelling demonstrate the valve's potential as a next-generation percutaneous prosthesis with the capacity for tissue self-maintenance and longevity. Regurgitation may be prevented by valve design optimisation.

  15. Can photovoltaic replace nuclear?

    International Nuclear Information System (INIS)

    2017-01-01

    As the French law on energy transition for a green growth predicts that one third of nuclear energy production is to be replaced by renewable energies (wind and solar) by 2025, and while the ADEME proposes a 100 per cent renewable scenario for 2050, this paper proposes a brief analysis of the replacement of nuclear energy by solar photovoltaic energy. It presents and discusses some characteristics of photovoltaic production: production level during a typical day for each month (a noticeable lower production in December), evolution of monthly production during a year, evolution of the rate between nuclear and photovoltaic production. A cost assessment is then proposed for energy storage and for energy production, and a minimum cost of replacement of nuclear by photovoltaic is assessed. The seasonal effect is outlined, as well as the latitude effect. Finally, the authors outline the huge cost of such a replacement, and consider that public support to new photovoltaic installations without an at least daily storage mean should be cancelled

  16. Thyroid hormone replacement therapy

    NARCIS (Netherlands)

    Wiersinga, W. M.

    2001-01-01

    Thyroid hormone replacement has been used for more than 100 years in the treatment of hypothyroidism, and there is no doubt about its overall efficacy. Desiccated thyroid contains both thyroxine (T(4)) and triiodothyronine (T(3)); serum T(3) frequently rises to supranormal values in the absorption

  17. Joint replacement in Zambia

    African Journals Online (AJOL)

    MJZ

    Objective: This paper presents the short-term findings from a joint replacement register started at the Zambian-Italian Orthopaedic Hospital (ZIOH) in Lusaka and compares the variables entered in this register with those captured in the Malawian. National Joint Register for purposes of synchronizing these in the near future ...

  18. Replacing Recipe Realism

    OpenAIRE

    Saatsi, J

    2017-01-01

    Many realist writings exemplify the spirit of ‘recipe realism’. Here I characterise recipe realism, challenge it, and propose replacing it with ‘exemplar realism’. This alternative understanding of realism is more piecemeal, robust, and better in tune with scientists’ own attitude towards their best theories, and thus to be preferred.

  19. Optimal composition of fluid-replacement beverages.

    Science.gov (United States)

    Baker, Lindsay B; Jeukendrup, Asker E

    2014-04-01

    The objective of this article is to provide a review of the fundamental aspects of body fluid balance and the physiological consequences of water imbalances, as well as discuss considerations for the optimal composition of a fluid replacement beverage across a broad range of applications. Early pioneering research involving fluid replacement in persons suffering from diarrheal disease and in military, occupational, and athlete populations incurring exercise- and/or heat-induced sweat losses has provided much of the insight regarding basic principles on beverage palatability, voluntary fluid intake, fluid absorption, and fluid retention. We review this work and also discuss more recent advances in the understanding of fluid replacement as it applies to various populations (military, athletes, occupational, men, women, children, and older adults) and situations (pathophysiological factors, spaceflight, bed rest, long plane flights, heat stress, altitude/cold exposure, and recreational exercise). We discuss how beverage carbohydrate and electrolytes impact fluid replacement. We also discuss nutrients and compounds that are often included in fluid-replacement beverages to augment physiological functions unrelated to hydration, such as the provision of energy. The optimal composition of a fluid-replacement beverage depends upon the source of the fluid loss, whether from sweat, urine, respiration, or diarrhea/vomiting. It is also apparent that the optimal fluid-replacement beverage is one that is customized according to specific physiological needs, environmental conditions, desired benefits, and individual characteristics and taste preferences.

  20. A replaceable liposomal aptamer for the ultrasensitive and rapid detection of biotin

    Science.gov (United States)

    Sung, Tzu-Cheng; Chen, Wen-Yih; Shah, Pramod; Chen, Chien-Sheng

    2016-02-01

    Biotin is an essential vitamin which plays an important role for maintaining normal physiological function. A rapid, sensitive, and simple method is necessary to monitor the biotin level. Here, we reported a replacement assay for the detection of biotin using a replaceable liposomal aptamer. Replacement assay is a competitive assay where a sample analyte replaces the labeled competitor of analyte out of its biorecognition element on a surface. It is user friendly and time-saving because of washing free. We used aptamer as a competitor, not a biorecognition element as tradition. To label aptamers, we used cholesterol-conjugated aptamers to tag signal-amplifying-liposomes. Without the need of conjugation procedure, aptamers can be easily incorporated into the surface of dye-encapsulating liposomes. Two aptamers as competitors of biotin, ST-21 and ST-21M with different affinities to streptavidin, were studied in parallel for the detection of biotin using replacement assays. ST-21 and ST-21M aptamers reached to limits of detection of 1.32 pg/80 μl and 0.47 pg/80 μl, respectively. The dynamic ranges of our assays using ST-21 and ST-21M aptamers were seven and four orders of magnitude, respectively. This assay can be completed in 20 minutes without washing steps. These results were overall better than previous reported assays.

  1. Androgen replacement therapy improves function in male rat muscles independently of hypertrophy and activation of the Akt/mTOR pathway.

    Science.gov (United States)

    Hourdé, C; Jagerschmidt, C; Clément-Lacroix, P; Vignaud, A; Ammann, P; Butler-Browne, G S; Ferry, A

    2009-04-01

    We analysed the effect of physiological doses of androgens following orchidectomy on skeletal muscle and bone of male rats, as well as the relationships between muscle performance, hypertrophy and the Akt/mammalian target of rapamycin (mTOR) signalling pathway involved in the control of anabolic and catabolic muscle metabolism. We studied the soleus muscle and tibia from intact rats (SHAM), orchidectomized rats treated for 3 months with vehicle (ORX), nandrolone decanoate (NAN) or dihydrotestosterone (DHT). Orchidectomy had very little effect on the soleus muscle. However, maximal force production by soleus muscle (+69%) and fatigue resistance (+35%) in NAN rats were both increased when compared with ORX rats. In contrast, DHT treatment did not improve muscle function. The relative number of muscle fibres expressing slow myosin heavy chain and citrate synthase activity were not different in NAN and ORX rats. Moreover, NAN and DHT treatments did not modify muscle weights and cross-sectional area of muscle fibres. Furthermore, phosphorylation levels of downstream targets of the Akt/mTOR signalling pathway, Akt, ribosomal protein S6 and eukaryotic initiation factor 4E-binding protein 1 were similar in muscles of NAN, DHT and ORX rats. In addition, trabecular tibia from NAN and DHT rats displayed higher bone mineral density and bone volume when compared with ORX rats. Only in NAN rats was this associated with increased bone resistance to fracture. Physiological doses of androgens are beneficial to muscle performance in orchidectomized rats without relationship to muscle and fibre hypertrophy and activation of the Akt/mTOR signalling pathway. Taken together our data clearly indicate that the activity of androgens on muscle and bone could participate in the global improvement of musculoskeletal status in the context of androgen deprivation induced by ageing.

  2. The effect of inhalation ofCitrus sinensisflowers andMentha spicataleave essential oils on lung function and exercise performance: a quasi-experimental uncontrolled before-and-after study.

    Science.gov (United States)

    Jaradat, Nidal Amin; Al Zabadi, Hamzeh; Rahhal, Belal; Hussein, Azmi Mahmoud Ali; Mahmoud, Jamal Shaker; Mansour, Basel; Khasati, Ahmad Ibrahim; Issa, Abdelkhaleq

    Recently, there has been an increased interest in the effects of essential oils on athletic performances and other physiological effects. This study aimed to assess the effects of Citrus sinensis flower and Mentha spicata leaves essential oils inhalation in two different groups of athlete male students on their exercise performance and lung function. Twenty physical education students volunteered to participate in the study. The subjects were randomly assigned into two groups: Mentha spicata and Citrus sinensis (ten participants each). One group was nebulized by Citrus sinensis flower oil and the other by Mentha spicata leaves oil in a concentration of (0.02 ml/kg of body mass) which was mixed with 2 ml of normal saline for 5 min before a 1500 m running tests. Lung function tests were measured using a spirometer for each student pre and post nebulization giving the same running distance pre and post oils inhalation. A lung function tests showed an improvement on the lung status for the students after inhaling of the oils. Interestingly, there was a significant increase in Forced Expiratory Volume in the first second and Forced Vital Capacity after inhalation for the both oils. Moreover significant reductions in the means of the running time were observed among these two groups. The normal spirometry results were 50 %, while after inhalation with M. spicata oil the ratio were 60 %. Our findings support the effectiveness of M. spicata and C. sinensis essential oils on the exercise performance and respiratory function parameters. However, our conclusion and generalisability of our results should be interpreted with caution due to small sample size and lack of control groups, randomization or masking. We recommend further investigations to explain the mechanism of actions for these two essential oils on exercise performance and respiratory parameters. ISRCTN10133422, Registered: May 3, 2016.

  3. Improved estimates of coordinate error for molecular replacement

    International Nuclear Information System (INIS)

    Oeffner, Robert D.; Bunkóczi, Gábor; McCoy, Airlie J.; Read, Randy J.

    2013-01-01

    A function for estimating the effective root-mean-square deviation in coordinates between two proteins has been developed that depends on both the sequence identity and the size of the protein and is optimized for use with molecular replacement in Phaser. A top peak translation-function Z-score of over 8 is found to be a reliable metric of when molecular replacement has succeeded. The estimate of the root-mean-square deviation (r.m.s.d.) in coordinates between the model and the target is an essential parameter for calibrating likelihood functions for molecular replacement (MR). Good estimates of the r.m.s.d. lead to good estimates of the variance term in the likelihood functions, which increases signal to noise and hence success rates in the MR search. Phaser has hitherto used an estimate of the r.m.s.d. that only depends on the sequence identity between the model and target and which was not optimized for the MR likelihood functions. Variance-refinement functionality was added to Phaser to enable determination of the effective r.m.s.d. that optimized the log-likelihood gain (LLG) for a correct MR solution. Variance refinement was subsequently performed on a database of over 21 000 MR problems that sampled a range of sequence identities, protein sizes and protein fold classes. Success was monitored using the translation-function Z-score (TFZ), where a TFZ of 8 or over for the top peak was found to be a reliable indicator that MR had succeeded for these cases with one molecule in the asymmetric unit. Good estimates of the r.m.s.d. are correlated with the sequence identity and the protein size. A new estimate of the r.m.s.d. that uses these two parameters in a function optimized to fit the mean of the refined variance is implemented in Phaser and improves MR outcomes. Perturbing the initial estimate of the r.m.s.d. from the mean of the distribution in steps of standard deviations of the distribution further increases MR success rates

  4. Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha is essential for human pancreatic beta cell function

    DEFF Research Database (Denmark)

    Hansen, Sara K; Párrizas, Marcelina; Jensen, Maria L

    2002-01-01

    , and consequently in reduced HNF-1alpha-dependent activation. These findings provide genetic evidence that HNF-1alpha serves as an upstream regulator of HNF-4alpha and interacts directly with the P2 promoter in human pancreatic cells. Furthermore, they indicate that this regulation is essential to maintain normal...... in human islets and exocrine cells is primarily mediated by the P2 promoter. Furthermore, we describe a G --> A mutation in a conserved nucleotide position of the HNF-1alpha binding site of the P2 promoter, which cosegregates with MODY. The mutation results in decreased affinity for HNF-1alpha...

  5. Principles of human joint replacement design and clinical application

    CERN Document Server

    Buechel, Frederick F

    2015-01-01

    This book is written for the users and designers of joint replacements. In its second extended edition it conveys to the reader the knowledge accumulated by the authors during their forty year effort on the development of replacement devices for the lower limb for the purpose of aiding the reader in their design and evaluation of joint replacement devices. The early chapters describe the engineering, scientific and medical principles needed for replacement joint evaluation. One must understand the nature and performance of the materials involved and their characteristics in vivo, i.e. the response of the body to implant materials. It is also essential to understand the response of the implants to applied loading and motion, particularly in the hostile physiological environment. A chapter describes the design methodology now required for joint replacement in the USA and EU countries. The remaining chapters provide a history of joint replacement, an evaluation of earlier and current devices and sample case hist...

  6. Principles of Human Joint Replacement Design and Clinical Application

    CERN Document Server

    Buechel, Frederick F

    2012-01-01

    Drs. Buechel, an orthopaedic surgeon, and Pappas, a professor of Mechanical Engineering, are the designers of several successful joint replacement systems. The most well-known of these is the pioneering LCS knee replacement. They have written this book for the users and designers of joint replacements. It is an attempt to convey to the reader the knowledge accumulated by the authors during their thirty five year effort on the development of replacement devices for the lower limb for the purpose of aiding the reader in their design and evaluation of joint replacement devices. The early chapters describe the engineering, scientific and medical principles needed for replacement joint evaluation. One must understand the nature and performance of the materials involved and their characteristics in vivo, i.e. the response of the body to implant materials. It is also essential to understand the response of the implants to applied loading and motion, particularly in the hostile physiological environment. A chapter de...

  7. Neuroimaging essentials in essential tremor: a systematic review.

    Science.gov (United States)

    Sharifi, Sarvi; Nederveen, Aart J; Booij, Jan; van Rootselaar, Anne-Fleur

    2014-01-01

    Essential tremor is regarded to be a disease of the central nervous system. Neuroimaging is a rapidly growing field with potential benefits to both diagnostics and research. The exact role of imaging techniques with respect to essential tremor in research and clinical practice is not clear. A systematic review of the different imaging techniques in essential tremor is lacking in the literature. We performed a systematic literature search combining the terms essential tremor and familial tremor with the following keywords: imaging, mri, vbm, dwi, fmri, pet and spect, both in abbreviated form as well as in full form. We summarize and discuss the quality and the external validity of each study and place the results in the context of existing knowledge regarding the pathophysiology of essential tremor. A total of 48 neuroimaging studies met our search criteria, roughly divided into 19 structural and 29 functional and metabolic studies. The quality of the studies varied, especially concerning inclusion criteria. Functional imaging studies indicated cerebellar hyperactivity during rest and during tremor. The studies also pointed to the involvement of the thalamus, the inferior olive and the red nucleus. Structural studies showed less consistent results. Neuroimaging techniques in essential tremor give insight into the pathophysiology of essential tremor indicating the involvement of the cerebellum as the most consistent finding. GABAergic dysfunction might be a major premise in the pathophysiological hypotheses. Inconsistencies between studies can be partly explained by the inclusion of heterogeneous patient groups. Improvement of scientific research requires more stringent inclusion criteria and application of advanced analysis techniques. Also, the use of multimodal neuroimaging techniques is a promising development in movement disorders research. Currently, the role of imaging techniques in essential tremor in daily clinical practice is limited.

  8. Planning for Sustainable Access to Technology: An Essential ...

    African Journals Online (AJOL)

    After they were used for a large number of procedures, it was clear that replacement instruments would be needed. The clinic manager requested replacements but was informed by the procurement officer that MVA was not included on the “essential equipment” list and, thus, additional authorisation would be necessary.

  9. ANTIMICROBIAL ACTIVITY OF THE ESSENTIAL OIL OF Myrtus ...

    African Journals Online (AJOL)

    2015-02-05

    Feb 5, 2015 ... a tendency to replace synthetic antimicrobials with natural alternative agents [1]. Plant based products are among the alternative agents examined in order to replace conventional antibiotics. Accordingly, extensive researches have been carried out in order to evaluate the antimicrobial effect of the essential ...

  10. On total disc replacement.

    Science.gov (United States)

    Berg, Svante

    2011-02-01

    Low back pain consumes a large part of the community's resources dedicated to health care and sick leave. Back disorders also negatively affect the individual leading to pain suffering, decreased quality-of-life and disability. Chronic low back pain (CLBP) due to degenerative disc disease (DDD) is today often treated with fusion when conservative treatment has failed and symptoms are severe. This treatment is as successful as arthroplasty is for hip arthritis in restoring the patient's quality of life and reducing disability. Even so, there are some problems with this treatment, one of these being recurrent CLBP from an adjacent segment (ASD) after primarily successful surgery. This has led to the development of alternative surgical treatments and devices that maintain or restore mobility, in order to reduce the risk for ASD. Of these new devices, the most frequently used are the disc prostheses used in Total Disc Replacement (TDR). This thesis is based on four studies comparing total disc replacement with posterior fusion. The studies are all based on a material of 152 patients with DDD in one or two segments, aged 20-55 years that were randomly treated with either posterior fusion or TDR. The first study concerned clinical outcome and complications. Follow-up was 100% at both one and two years. It revealed that both treatment groups had a clear benefit from treatment and that patients with TDR were better in almost all outcome scores at one-year follow-up. Fusion patients continued to improve during the second year. At two-year follow-up there was a remaining difference in favour of TDR for back pain. 73% in the TDR group and 63% in the fusion group were much better or totally pain-free (n.s.), while twice as many patients in the TDR group were totally pain free (30%) compared to the fusion group (15%). Time of surgery and total time in hospital were shorter in the TDR group. There was no difference in complications and reoperations, except that seventeen of the

  11. Urban chaos and replacement dynamics in nature and society

    Science.gov (United States)

    Chen, Yanguang

    2014-11-01

    Replacements resulting from competition are ubiquitous phenomena in both nature and society. The evolution of a self-organized system is always a physical process substituting one type of components for another type of components. A logistic model of replacement dynamics has been proposed in terms of technical innovation and urbanization, but it fails to arouse widespread attention in the academia. This paper is devoted to laying the foundations of general replacement principle by using analogy and induction. The empirical base of this study is urban replacement, including urbanization and urban growth. The sigmoid functions can be employed to model various processes of replacement. Many mathematical methods such as allometric scaling and head/tail breaks can be applied to analyzing the processes and patterns of replacement. Among varied sigmoid functions, the logistic function is the basic and the simplest model of replacement dynamics. A new finding is that replacement can be associated with chaos in a nonlinear system, e.g., urban chaos is just a part of replacement dynamics. The aim of developing replacement theory is at understanding complex interaction and conversion. This theory provides a new way of looking at urbanization, technological innovation and diffusion, Volterra-Lotka’s predator-prey interaction, man-land relation, and dynastic changes resulting from peasant uprising, and all that. Especially, the periodic oscillations and chaos of replacement dynamics can be used to explain and predict the catastrophic occurrences in the physical and human systems.

  12. Essential real analysis

    CERN Document Server

    Field, Michael

    2017-01-01

    This book provides a rigorous introduction to the techniques and results of real analysis, metric spaces and multivariate differentiation, suitable for undergraduate courses. Starting from the very foundations of analysis, it offers a complete first course in real analysis, including topics rarely found in such detail in an undergraduate textbook such as the construction of non-analytic smooth functions, applications of the Euler-Maclaurin formula to estimates, and fractal geometry.  Drawing on the author’s extensive teaching and research experience, the exposition is guided by carefully chosen examples and counter-examples, with the emphasis placed on the key ideas underlying the theory. Much of the content is informed by its applicability: Fourier analysis is developed to the point where it can be rigorously applied to partial differential equations or computation, and the theory of metric spaces includes applications to ordinary differential equations and fractals. Essential Real Analysis will appeal t...

  13. Genetics of essential hypertension.

    Science.gov (United States)

    Mein, Charles A; Caulfield, Mark J; Dobson, Richard J; Munroe, Patricia B

    2004-04-01

    Essential hypertension affects 1 billion people worldwide and its genetic basis is well established. For this review we surveyed the literature on the genetics of hypertension during the past 18 months and we now report the highlights. There has been publication of the two largest genome scans for blood pressure and new loci including significant linkage to chromosome 6q have been reported. The molecular basis of Gordon's syndrome has been partially unravelled with a dual function for WNK4 in ion transport regulation being discovered. There has also been progress in narrowing rodent quantitative trait loci using congenic approaches and several linkage peaks have now been demonstrated to have more than one loci. We also report some of the initial findings from pharmacogenetic studies.

  14. Aortic valve replacement

    DEFF Research Database (Denmark)

    Kapetanakis, Emmanouil I; Athanasiou, Thanos; Mestres, Carlos A

    2008-01-01

    BACKGROUND AND AIMS OF THE STUDY: Prompted by anecdotal evidence and observations by surgeons, an investigation was undertaken into the potential differences in implanted aortic valve prosthesis sizes, during aortic valve replacement (AVR) procedures, between northern and southern European...... assigned to the 'small' aortic size subset. Effective orifice area indices were calculated for all patients to assess the geographic distribution of patient-prosthesis mismatch. Univariable and multivariable logistic regression analyses adjusting for possible confounding variables were performed. RESULTS...

  15. The replacement research reactor

    International Nuclear Information System (INIS)

    Cameron, R.; Horlock, K.

    2001-01-01

    The contract for the design, construction and commissioning of the Replacement Research Reactor was signed in July 2000. This was followed by the completion of the detailed design and an application for a construction licence was made in May 2001. This paper will describe the main elements of the design and their relation to the proposed applications of the reactor. The future stages in the project leading to full operation are also described

  16. Osteoblast and osteoclast behaviors in the turnover of attachment bones during medaka tooth replacement.

    Science.gov (United States)

    Mantoku, Akiko; Chatani, Masahiro; Aono, Kazushi; Inohaya, Keiji; Kudo, Akira

    2016-01-15

    Tooth replacement in polyphyodont is a well-organized system for maintenance of homeostasis of teeth, containing the dynamic structural change in skeletal tissues such as the attachment bone, which is the supporting element of teeth. Histological analyses have revealed the character of tooth replacement, however, the cellular mechanism of how skeletal tissues are modified during tooth replacement is largely unknown. Here, we showed the important role of osteoblasts for controlling osteoclasts to modify the attachment bone during tooth replacement in medaka pharyngeal teeth, coupled with an osterix-DsRed/TRAP-GFP transgenic line to visualize osteoblasts and osteoclasts. In the turnover of the row of attachment bones, these bones were resorbed at the posterior side where most developed functional teeth were located, and generated at the anterior side where teeth were newly erupted, which caused continuous tooth replacement. In the cellular analysis, osteoclasts and osteoblasts were located at attachment bones separately, since mature osteoclasts were localized at the resorbing side and osteoblasts gathered at the generating side. To demonstrate the role of osteoclasts in tooth replacement, we established medaka made deficient in c-fms-a by TALEN. c-fms-a deficient medaka showed hyperplasia of attachment bones along with reduced bone resorption accompanied by a low number of TRAP-positive osteoclasts, indicating an important role of osteoclasts in the turnover of attachment bones. Furthermore, nitroreductase-mediated osteoblast-specific ablation induced disappearance of osteoclasts, indicating that osteoblasts were essential for maintenance of osteoclasts for the proper turnover. Taken together, our results suggested that the medaka attachment bone provides the model to understand the cellular mechanism for tooth replacement, and that osteoblasts act in the coordination of bone morphology by supporting osteoclasts. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. DNase I Hypersensitive Site II of the Human Growth Hormone Locus Control Region Mediates an Essential and Distinct Long-range Enhancer Function*

    Science.gov (United States)

    Fleetwood, Margaret R.; Ho, Yugong; Cooke, Nancy E.; Liebhaber, Stephen A.

    2012-01-01

    Locus control regions (LCRs) comprise sets of DNA elements capable of establishing autonomous chromatin domains that support robust and physiologically appropriate expression of target genes, often working over extensive distances. Human growth hormone (hGH-N) expression in the pituitary is under the regulation of a well characterized LCR containing four DNase I hypersensitive sites (HSs). The two pituitary-specific HS, HSI and HSII, are located 14.5 and 15.5 kb 5′ to the hGH-N promoter. HSI is essential for activation of hGH-N during pituitary development and for sustaining robust activity in the adult. To determine whether the closely linked HSII has a role in hGH-N expression, it was deleted from a previously validated hGH/P1 transgene. Analysis of three independent hGH/P1(ΔHSII) transgenic mouse lines revealed that this deletion had no adverse effect on the formation of HSI, yet resulted in a substantial loss (70%) in hGH-N mRNA expression. This loss of expression was accompanied by a corresponding reduction in recruitment of the pituitary-specific transcription factor Pit-1 to the hGH-N promoter and a selective decrease in promoter occupancy of the elongation-linked isoform of RNA polymerase II. Sufficiency of HSI and HSII in LCR activity was explored by establishing two additional sets of mouse transgenic lines in which DNA segments containing these HS were positioned within the λ phage genome. In this “neutral” DNA context, HSII was required for the recruitment of HAT activity. These data establish HSII as a nonredundant component of the hGH LCR essential for establishment of robust levels of hGH-N gene expression. PMID:22669946

  18. DNase I hypersensitive site II of the human growth hormone locus control region mediates an essential and distinct long-range enhancer function.

    Science.gov (United States)

    Fleetwood, Margaret R; Ho, Yugong; Cooke, Nancy E; Liebhaber, Stephen A

    2012-07-20

    Locus control regions (LCRs) comprise sets of DNA elements capable of establishing autonomous chromatin domains that support robust and physiologically appropriate expression of target genes, often working over extensive distances. Human growth hormone (hGH-N) expression in the pituitary is under the regulation of a well characterized LCR containing four DNase I hypersensitive sites (HSs). The two pituitary-specific HS, HSI and HSII, are located 14.5 and 15.5 kb 5' to the hGH-N promoter. HSI is essential for activation of hGH-N during pituitary development and for sustaining robust activity in the adult. To determine whether the closely linked HSII has a role in hGH-N expression, it was deleted from a previously validated hGH/P1 transgene. Analysis of three independent hGH/P1(ΔHSII) transgenic mouse lines revealed that this deletion had no adverse effect on the formation of HSI, yet resulted in a substantial loss (70%) in hGH-N mRNA expression. This loss of expression was accompanied by a corresponding reduction in recruitment of the pituitary-specific transcription factor Pit-1 to the hGH-N promoter and a selective decrease in promoter occupancy of the elongation-linked isoform of RNA polymerase II. Sufficiency of HSI and HSII in LCR activity was explored by establishing two additional sets of mouse transgenic lines in which DNA segments containing these HS were positioned within the λ phage genome. In this "neutral" DNA context, HSII was required for the recruitment of HAT activity. These data establish HSII as a nonredundant component of the hGH LCR essential for establishment of robust levels of hGH-N gene expression.

  19. Effects of a face-to-face self-management program on knowledge, self-care practice and kidney function in patients with chronic kidney disease before the renal replacement therapy.

    Science.gov (United States)

    Choi, Eun Sung; Lee, Jia

    2012-12-01

    The purpose of this study was to examine the effects of a face-to-face self-management educational program on knowledge, self-care practice and kidney function in patients with chronic kidney disease (CKD) before kidney replacement therapy. This study employed a nonequivalent control group, non-synchronized design. Data were collected from 61 patients with CKD visiting an outpatient department of nephrology in a university hospital in Seoul, South Korea. The experimental group (n=31) took the pre-test, then after 3 weeks, face-to-face education and individualized consultation (1st intervention), after a week of self-practice, the 1st post-test, followed by re-enforcement education and consultation (2nd intervention), and 4 weeks later, the 2nd post-test. The control group (n=30) took the pre-test and post-tests at 4 and 8 weeks. Scores for knowledge of CKD and self-care practice over time improved significantly in the experimental group compared to the control group. Kidney function did not improve significantly in the experimental group. Health care providers can identify various and individualized needs, and provide effective education and consultation through face to face self-management for patients with chronic irreversible illnesses. Nurses can coordinate for these program by designing and providing systematic and effective education.

  20. Redundant function of REV-ERBalpha and beta and non-essential role for Bmal1 cycling in transcriptional regulation of intracellular circadian rhythms.

    Directory of Open Access Journals (Sweden)

    Andrew C Liu

    2008-02-01

    Full Text Available The mammalian circadian clockwork is composed of a core PER/CRY feedback loop and additional interlocking loops. In particular, the ROR/REV/Bmal1 loop, consisting of ROR activators and REV-ERB repressors that regulate Bmal1 expression, is thought to "stabilize" core clock function. However, due to functional redundancy and pleiotropic effects of gene deletions, the role of the ROR/REV/Bmal1 loop has not been accurately defined. In this study, we examined cell-autonomous circadian oscillations using combined gene knockout and RNA interference and demonstrated that REV-ERBalpha and beta are functionally redundant and are required for rhythmic Bmal1 expression. In contrast, the RORs contribute to Bmal1 amplitude but are dispensable for Bmal1 rhythm. We provide direct in vivo genetic evidence that the REV-ERBs also participate in combinatorial regulation of Cry1 and Rorc expression, leading to their phase-delay relative to Rev-erbalpha. Thus, the REV-ERBs play a more prominent role than the RORs in the basic clock mechanism. The cellular genetic approach permitted testing of the robustness of the intracellular core clock function. We showed that cells deficient in both REV-ERBalpha and beta function, or those expressing constitutive BMAL1, were still able to generate and maintain normal Per2 rhythmicity. Our findings thus underscore the resilience of the intracellular clock mechanism and provide important insights into the transcriptional topologies underlying the circadian clock. Since REV-ERB function and Bmal1 mRNA/protein cycling are not necessary for basic clock function, we propose that the major role of the ROR/REV/Bmal1 loop and its constituents is to control rhythmic transcription of clock output genes.

  1. Annual report for Ion Replacement Program

    Energy Technology Data Exchange (ETDEWEB)

    Tomczuk, Z.; Willit, J.L.; Fischer, A.K.

    1993-07-01

    Ion replacement electrorefining is an innovative electrochemical approach to purifying and separating metals. This approach overcomes the shortcomings of conventional electrorefining and has the potential for processing a wider range of metals and metal halide salts. Salt waste is also minimized with this approach. The key element of ion replacement electrorefining is the ion replacement electrode. This electrode allows a decoupling of the electrotransport process into two separate steps, anodic dissolution and cathodic deposition. Three key accomplishments described in this report that demonstrate the feasibility of ion replacement electrorefining are: (1) we have identified a suitable sodium/{beta}{double_prime}-alumina/molten salt electrolyte system that functions reproducibly at 723 K, (2) we have oxidized and deposited dysprosium, lanthanum, uranium, and titanium by using a sodium ion replacement electrode. In several experiments, an actual separation of dysprosium and lanthanum was observed, and (3) we have identified a metal alloy, Li{sub x}Sb, as an alternative ion replacement electrode. The next stage in the program is the design, construction, and testing of a laboratory-scale electrorefiner. Follow-on development with funding from industrial and federal sponsors is being pursued.

  2. The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation

    DEFF Research Database (Denmark)

    Becker-Heck, Anita; Zohn, Irene E; Okabe, Noriko

    2011-01-01

    Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with the abnormal function of motile cilia. Approximately half of individuals with PCD also have alterations in the left-right org...

  3. The N-terminal domain of APJ, a CNS-based coreceptor for HIV-1, is essential for its receptor function and coreceptor activity

    International Nuclear Information System (INIS)

    Zhou Naiming; Zhang Xiaoling; Fan Xuejun; Argyris, Elias; Fang Jianhua; Acheampong, Edward; DuBois, Garrett C.; Pomerantz, Roger J.

    2003-01-01

    The human APJ, a G protein-coupled seven-transmembrane receptor, has been found to be dramatically expressed in the human central nervous system (CNS) and also to serve as a coreceptor for the entry of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV). Studies with animal models suggested that APJ and its natural ligand, apelin, play an important role in the central control of body fluid homeostasis, and in regulation of blood pressure and cardiac contractility. In this study, we characterize the structural and functional determinants of the N-terminal domain of APJ in interactions with its natural ligand and HIV-1 envelope glycoprotein. We demonstrate that the second 10 residues of the N-terminal domain of APJ are critical for association with apelin, while the first 20 amino acids play an important role in supporting cell-cell fusion mediated by HIV-1 gp120. With site-directed mutagenesis, we have identified that the negatively charged amino acid residues Glu20 and Asp23 are involved in receptor and coreceptor functions, but residues Tyr10 and Tyr11 substantially contribute to coreceptor function for both T-tropic (CXCR4) and dual-tropic (CXCR4 and CCR5) HIV-1 isolates. Thus, this study provides potentially important information for further characterizing APJ-apelin functions in vitro and in vivo and designing small molecules for treatment of HIV-1 infection in the CNS

  4. Essential gains and health after upper-limb tetraplegia surgery identified by the International classification of functioning, disability and health (ICF).

    Science.gov (United States)

    Bunketorp-Käll, L; Reinholdt, C; Fridén, J; Wangdell, J

    2017-09-01

    A questionnaire-based survey. To describe functional gains and health following upper-limb tetraplegia surgery using the International Classification of Functioning, Disability and Health (ICF) as a reference and to explore interconnections across different dimensions of functioning and health. A specialized center for advanced reconstruction of extremities at Sahlgrenska University Hospital, Gothenburg, Sweden. Fifty-seven individuals who participated in a satisfaction survey were included in the present study. Besides questions concerned with the respondents' satisfaction with different aspects of surgery, the measures included perceived overall health status (EQ-VAS) and achieved grip strength. Univariate analyses were used to explore interconnections between measures. The gains could be subcategorized and linked to the ICF domains 'mobility', 'self-care', 'communication', 'domestic life', and 'community, social and civic life', with 'handling objects' and 'maneuvering a wheelchair' as the most frequently reported gains. The mean EQ-VAS score was 67±22. No significant correlation was shown between grip strength and activity gains, nor between grip strength and perceived overall health. The degree of satisfaction was, however, associated with self-reported overall health among participants. The functional gains achieved after tetraplegia surgery could be applied to the ICF constructs' body functions/structures and activity with possible implications on participation. The overall health perception was relatively high and could be linked to the degree of satisfaction among participants. Muscle strength is not necessarily transferable to activity performance. This emphasizes the importance of addressing factors other than strength in the post-surgical rehabilitation and assessments.

  5. An evolutionarily conserved arginine is essential for Tre1 G protein-coupled receptor function during germ cell migration in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Angela R Kamps

    Full Text Available BACKGROUND: G protein-coupled receptors (GPCRs play central roles in mediating cellular responses to environmental signals leading to changes in cell physiology and behaviors, including cell migration. Numerous clinical pathologies including metastasis, an invasive form of cell migration, have been linked to abnormal GPCR signaling. While the structures of some GPCRs have been defined, the in vivo roles of conserved amino acid residues and their relationships to receptor function are not fully understood. Trapped in endoderm 1 (Tre1 is an orphan receptor of the rhodopsin class that is necessary for primordial germ cell migration in Drosophila melanogaster embryos. In this study, we employ molecular genetic approaches to identify residues in Tre1 that are critical to its functions in germ cell migration. METHODOLOGY/PRINCIPAL FINDINGS: First, we show that the previously reported scattershot mutation is an allele of tre1. The scattershot allele results in an in-frame deletion of 8 amino acids at the junction of the third transmembrane domain and the second intracellular loop of Tre1 that dramatically impairs the function of this GPCR in germ cell migration. To further refine the molecular basis for this phenotype, we assayed the effects of single amino acid substitutions in transgenic animals and determined that the arginine within the evolutionarily conserved E/N/DRY motif is critical for receptor function in mediating germ cell migration within an intact developing embryo. CONCLUSIONS/SIGNIFICANCE: These structure-function studies of GPCR signaling in native contexts will inform future studies into the basic biology of this large and clinically important family of receptors.

  6. REPLACEMENT OF FRENCH CARDS

    CERN Multimedia

    Human Resources Division

    2001-01-01

    The French Ministry of Foreign Affairs has informed the Organization that it is shortly to replace all diplomatic cards, special cards and employment permits ('attestations de fonctions') now held by members of the personnel and their families. Between 2 July and 31 December 2001, these cards are to be replaced by secure, computerized equivalents. A 'personnel office' stamped photocopy of the old cards may continue to be used until 31 December 2001. For the purposes of the handover, members of the personnel must go personally to the cards office (33/1-015), between 8:30 and 12:30, in order to fill a 'fiche individuelle' form (in black ink only), which has to be personally signed by themselves and another separately signed by members of their family, taking the following documents for themselves and members of their families already in possession of a French card : A recent identity photograph in 4.5 cm x 3.5 cm format (signed on the back) The French card in their possession an A4 photocopy of the same Fre...

  7. Total disc replacement.

    Science.gov (United States)

    Vital, J-M; Boissière, L

    2014-02-01

    Total disc replacement (TDR) (partial disc replacement will not be described) has been used in the lumbar spine since the 1980s, and more recently in the cervical spine. Although the biomechanical concepts are the same and both are inserted through an anterior approach, lumbar TDR is conventionally indicated for chronic low back pain, whereas cervical TDR is used for soft discal hernia resulting in cervicobrachial neuralgia. The insertion technique must be rigorous, with precise centering in the disc space, taking account of vascular anatomy, which is more complex in the lumbar region, particularly proximally to L5-S1. All of the numerous studies, including prospective randomized comparative trials, have demonstrated non-inferiority to fusion, or even short-term superiority regarding speed of improvement. The main implant-related complication is bridging heterotopic ossification with resulting loss of range of motion and increased rates of adjacent segment degeneration, although with an incidence lower than after arthrodesis. A sufficiently long follow-up, which has not yet been reached, will be necessary to establish definitively an advantage for TDR, particularly in the cervical spine. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. Cadmium plating replacements

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, M.J.; Groshart, E.C.

    1995-03-01

    The Boeing Company has been searching for replacements to cadmium plate. Two alloy plating systems seem close to meeting the needs of a cadmium replacement. The two alloys, zinc-nickel and tin-zinc are from alloy plating baths; both baths are neutral pH. The alloys meet the requirements for salt fog corrosion resistance, and both alloys excel as a paint base. Currently, tests are being performed on standard fasteners to compare zinc-nickel and tin-zinc on threaded hardware where cadmium is heavily used. The Hydrogen embrittlement propensity of the zinc-nickel bath has been tested, and just beginning for the tin-zinc bath. Another area of interest is the electrical properties on aluminum for tin-zinc and will be discussed. The zinc-nickel alloy plating bath is in production in Boeing Commercial Airplane Group for non-critical low strength steels. The outlook is promising that these two coatings will help The Boeing Company significantly reduce its dependence on cadmium plating.

  9. Power Plant Replacement Study

    Energy Technology Data Exchange (ETDEWEB)

    Reed, Gary

    2010-09-30

    This report represents the final report for the Eastern Illinois University power plant replacement study. It contains all related documentation from consideration of possible solutions to the final recommended option. Included are the economic justifications associated with the chosen solution along with application for environmental permitting for the selected project for construction. This final report will summarize the results of execution of an EPC (energy performance contract) investment grade audit (IGA) which lead to an energy services agreement (ESA). The project includes scope of work to design and install energy conservation measures which are guaranteed by the contractor to be self-funding over its twenty year contract duration. The cost recovery is derived from systems performance improvements leading to energy savings. The prime focus of this EPC effort is to provide a replacement solution for Eastern Illinois University’s aging and failing circa 1925 central steam production plant. Twenty-three ECMs were considered viable whose net impact will provide sufficient savings to successfully support the overall project objectives.

  10. REPLACEMENT OF FRENCH CARDS

    CERN Document Server

    HR/SOC

    2001-01-01

    The French Ministry of Foreign Affairs has informed the Organization that it is shortly to replace all diplomatic cards, special cards and employment permits ('attestations de fonctions') now held by members of the personnel and their families. Between 2 July and 31 December 2001, these cards are to be replaced by secure, computerized equivalents. The old cards may continue to be used until 31 December 2001. For the purposes of the handover, members of the personnel must go personally to the cards office (33/1-015), in order to fill in a 'fiche individuelle' form, taking the following documents for themselves and members of their families already in possession of a French card : A recent identity photograph in 4.5 cm x 3.5 cm format. The French card in their possession. An A4 photocopy of the same French card, certified by the cards office as being a true copy. Those members of the personnel whose cards (and/or cards belonging to members of their families) are shortly due to expire, or have recently done...

  11. REPLACEMENT OF FRENCH CARDS

    CERN Document Server

    Human Resources Division; Cards.Service@cern.ch

    2001-01-01

    The French Ministry of Foreign Affairs is currently replacing all diplomatic cards, special cards and employment permits («attestations de fonctions») held by members of the personnel and their families. These cards are replaced by secure, computerized equivalents. The old cards may no longer be used after 31 December 2001. For the purposes of the handover, members of the personnel must go personally to the cards office (33/1-015) between 8h30 and 12h30, in order to fill in a «fiche individuelle» form, taking the following documents for themselves and members of their families already in possession of a French card : A recent identity photograph in 4.5 cm x 3.5 cm format, the French card in their possession, an A4 photocopy of the same French card, certified by the cards office as being a true copy. Those members of the personnel whose cards (and/or cards belonging to members of their families) are shortly due to expire, or have recently done so, are also requested...

  12. REPLACEMENT OF FRENCH CARDS

    CERN Multimedia

    Human Resources Division

    2001-01-01

    The French Ministry of Foreign Affairs has informed the Organization that it is shortly to replace all diplomatic cards, special cards and employment permits ('attestations de fonctions') now held by members of the personnel and their families. Between 2 July and 31 December 2001, these cards are to be replaced by secure, computerized equivalents. The old cards may continue to be used until 31 December 2001. For the purposes of the handover, members of the personnel are asked to go to the cards office (33/1-015), taking the following documents for themselves and members of their families already in possession of a French card : A recent identity photograph in 4.5 cm x 3.5 cm format, The French card in their possession, an A4 photocopy of the same French card, certified by the cards office as being a true copy. Those members of the personnel whose cards (and/or cards belonging to members of their families) are shortly due to expire, or have recently done so, are also requested to take these items to the c...

  13. The Replacement Operation for CCP Programs

    NARCIS (Netherlands)

    Bertolino, Marco; Etalle, Sandro; Palamidessi, Catuscia

    1999-01-01

    The Replacement is a very powerful transformation operation which - both within the functional paradigm as well as within the logic programming one - can micic the most common transformation operations such as unfold, fold, switching, distribution. Because of this flexibility , it can be incorrect

  14. The Replacement Operation for CCP Programs

    NARCIS (Netherlands)

    Bertolino, Marco; Bossi, Annalisa; Etalle, Sandro; Palamidessi, Catuscia

    2000-01-01

    The Replacement is a very powerful transformation operation which - both within the functional paradigm as well as within the logic programming one - can micic the most common transformation operations such as unfold, fold, switching, distribution. Because of this flexibility , it can be incorrect

  15. Joint Replacement (Finger and Wrist Joints)

    Science.gov (United States)

    ... wrist joints can all be replaced (Figure 1). Artificial joints in the hand may help: Reduce joint pain Restore or maintain joint motion Improve the look and alignment of the joint(s) Improve overall hand function Causes In a normal joint, bones have a smooth surface made of a substance ...

  16. Platelet-derived growth factor B retention is essential for development of normal structure and function of conduit vessels and capillaries

    DEFF Research Database (Denmark)

    Nyström, Henrik C.; Lindblom, Per; Wickman, Anna

    2006-01-01

    : Passive and active properties of conduit vessels were studied using myograph techniques and histological examination. Capillary structure and function was studied using measurements of capillary density in skeletal muscle and by assessing aerobic physical performance in a treadmill setup. Cardiac function...... was assessed using echocardiography. RESULTS: Myograph experiments revealed an increased diameter and stiffness of the aorta in RetKO. Histological examination showed increased media collagen content and a decreased number of aortic wall layers, however with a similar number of vascular smooth muscle cells....... This outward eutrophic remodelling of the aorta was accompanied by endothelial dysfunction. RetKO showed decreased capillary density in skeletal muscle and signs of a defective delivery of capillary oxygen to skeletal muscle, as shown by a decreased physical performance. In RetKO mice, echocardiography...

  17. Direct repeat sequences are essential for function of the cis-acting locus of transfer (clt) of Streptomyces phaeochromogenes plasmid pJV1.

    Science.gov (United States)

    Franco, Bernardo; González-Cerón, Gabriela; Servín-González, Luis

    2003-11-01

    The functionality of direct and inverted repeat sequences inside the cis acting locus of transfer (clt) of the Streptomyces plasmid pJV1 was determined by testing the effect of different deletions on plasmid transfer. The results show that the single most important element for pJV1 clt function is a series of evenly spaced 9 bp long direct repeats which match the consensus CCGCACA(C/G)(C/G), since their deletion caused a dramatic reduction in plasmid transfer. The presence of these repeats in the absence of any other clt sequences allowed plasmid transfer to occur at a frequency that was at least two orders of magnitude higher than that obtained in the complete absence of clt. A database search revealed regions with a similar organization, and in the same position, in Streptomyces plasmids pSN22 and pSLS, which have transfer proteins homologous to those of pJV1.

  18. Knee joint replacement prosthesis (image)

    Science.gov (United States)

    A prosthesis is a device designed to replace a missing part of the body, or to make a part of the body work better. The metal prosthetic device in knee joint replacement surgery replaces cartilage and bone which is damaged from disease or aging.

  19. Essential Function for PDLIM2 in Cell Polarization in Three-Dimensional Cultures by Feedback Regulation of the β1-Integrin–RhoA Signaling Axis

    Directory of Open Access Journals (Sweden)

    Ravi Kiran Deevi

    2014-05-01

    Full Text Available PDLIM2 is a cytoskeletal and nuclear PDZ-LIM domain protein that regulates the stability of Nuclear Factor kappa-B (NFκB and other transcription factors, and is required for polarized cell migration. PDLIM2 expression is suppressed by methylation in different cancers, but is strongly expressed in invasive breast cancer cells that have undergone an Epithelial Mesenchymal Transition (EMT. PDLIM2 is also expressed in non-transformed breast myoepithelial MCF10A cells and here we asked whether it is important for maintaining the polarized, epithelial phenotype of these cells. Suppression of PDLIM2 in MCF10A cells was sufficient to disrupt cell polarization and acini formation with increased proliferation and reduced apoptosis in the luminal space compared to control acini with hollow lumina. Spheroids with suppressed PDLIM2 exhibited increased expression of cell-cell and cell-matrix adhesion proteins including beta 1 (β1 integrin. Interestingly, levels of the Insulin-like growth factor 1 receptor (IGF-1 R and Receptor of activated protein kinase C 1 (RACK1, which scaffolds IGF-1R to β1 integrin, were also increased, indicating a transformed phenotype. Focal Adhesion Kinase (FAK and cofilin phosphorylation, and RhoA Guanosine Triphosphatase (GTPase activity were all enhanced in these spheroids compared to control acini. Importantly, inhibition of either FAK or Rho Kinase (ROCK was sufficient to rescue the polarity defect. We conclude that PDLIM2 expression is essential for feedback regulation of the β1-integrin-RhoA signalling axis and integration of cellular microenvironment signals with gene expression to control the polarity of breast epithelial acini structures. This is a mechanism by which PDLIM2 could mediate tumour suppression in breast epithelium.

  20. Functional morphology of pituitary -thyroid and -adrenocortical axes in middle-aged male rats treated with Vitex agnus castus essential oil.

    Science.gov (United States)

    Šošić-Jurjević, Branka; Ajdžanović, Vladimir; Filipović, Branko; Trifunović, Svetlana; Jarić, Ivana; Ristić, Nataša; Milošević, Verica

    2016-09-01

    We previously reported that Vitex agnus-castus L. essential oil (VACEO), when administered to middle-aged males, exerts a bone-protective effect, induces silencing of locomotor activities and decreases pituitary prolactin immunopositivity. To further assess the putative endocrine effects of VACEO, we examined the pituitary-thyroid and -adrenocortical axes in our model. Sixteen-month-old Wistar rats were subcutaneously administered 60mg/kg of VACEO dissolved in sterile olive oil, while the control group received the same amount of vehicle alone for three weeks. Pituitaries, thyroids and adrenals were analyzed by qualitative and quantitative histological approaches. Concentration of thyroid stimulating hormone (TSH), total thyroxine and triiodothyronine (TH), adrenocorticotrophic hormone (ACTH), corticosterone in serum and in adrenal tissue were measured. In VACEO-treated rats, the relative volume density of pituitary thyrotrophs increased (p<0.001), while intensity of cytoplasmic TSHβ immunostaining decreased (p<0.001), consistent with elevated TSH in serum (p<0.01). The thyroid tissue was characterized by a micro-follicular structure, increased relative volume of follicular epithelium (p<0.05), decreased volume of luminal colloid (p<0.001) and increased basolateral expression of sodium-iodide symporter-immunopositivity (p<0.05). Serum TH also increased (p<0.01). The relative volume density of pituitary corticotrophs decreased (p<0.05), compatible with decline in circulating ACTH (p<0.05). Neither tissue nor serum corticosterone levels were affected by VACEO treatment. In conclusion, the observed changes in TSH and ACTH strongly indicate central endocrine effects of prolonged VACEO treatment. In this respect, production of ACTH decreased without impact on corticosterone production. Increase in serum concentration of both TH and TSH are not compatible with a negative feedback loop and suggest a major change in set-point regulation of the hypothalamic

  1. Essential amino acid enriched high-protein enteral nutrition modulates insulin-like growth factor-1 system function in a rat model of trauma-hemorrhagic shock.

    Directory of Open Access Journals (Sweden)

    Xianfeng Xia

    Full Text Available Nutrition support for critically ill patients supplemented with additional modular protein may promote skeletal muscle protein anabolism in addition to counteracting acute nitrogen loss. The present study was designed to investigate whether the essential amino acid (EAA enriched high-protein enteral nutrition (EN modulates the insulin-like growth factor-1 (IGF-1 system and activates the mammalian target of rapamycin (mTOR anabolic signaling pathway in a trauma-hemorrhagic shock (T-HS rat model.Male Sprague-Dawley rats (n = 90, 278.18 ± 0.94 g were randomly assigned to 5 groups: (1 normal control, (2 pair-fed, (3 T-HS, (4 T-HS and standard EN, and (5 T-HS and EAA enriched high-protein EN. Six animals from each group were harvested on days 2, 4, and 6 for serum, gastrocnemius, soleus, and extensor digitorum longus sample collection. T-HS significantly reduced muscle mass. Nutrition support maintained muscle mass, especially the EAA enriched high-protein EN. Meanwhile, a pronounced derangement in IGF-1-IGFBPs axis as well as impaired mTOR transduction was observed in the T-HS group. Compared with animals receiving standard EN, those receiving EAA enriched high-protein EN presented 18% higher serum free IGF-1 levels following 3 days of nutrition support and 22% higher after 5 days. These changes were consistent with the concomitant elevation in serum insulin and reduction in corticosterone levels. In addition, phosphorylations of downstream anabolic signaling effectors - including protein kinase B, mTOR, and ribosomal protein S6 kinase1 - increased significantly in rats receiving EAA enriched high-protein EN.Our findings firstly demonstrate the beneficial effect of EAA enriched high-protein EN on the metabolic modulation of skeletal muscle protein anabolism by regulating the IGF-1 system and downstream anabolic signaling transduction.

  2. Provider perspectives on essential functions for care management in the collaborative treatment of hypertension: the P.A.R.T.N.E.R. framework.

    Science.gov (United States)

    Hussain, Tanvir; Allen, Allyssa; Halbert, Jennifer; Anderson, Cheryl A M; Boonyasai, Romsai Tony; Cooper, Lisa A

    2015-04-01

    Care management has become a widespread strategy for improving chronic illness care. However, primary care provider (PCP) participation in programs has been poor. Because the success of care management relies on provider engagement, understanding provider perspectives is necessary. Our goal was to identify care management functions most valuable to PCPs in hypertension treatment. Six focus groups were conducted to discuss current challenges in hypertension care and identify specific functions of care management that would improve care. The study included 39 PCPs (participation rate: 83 %) representing six clinics, two of which care for large African American populations and four that are in underserved locations, in the greater Baltimore metropolitan area. This was a qualitative analysis of focus groups, using grounded theory and iterative coding. Providers desired achieving blood pressure control more rapidly. Collaborating with care managers who obtain ongoing patient data would allow treatment plans to be tailored to the changing life conditions of patients. The P.A.R.T.N.E.R. framework summarizes the care management functions that providers reported were necessary for effective collaboration: Partner with patients, providers, and the community; Arrange follow-up care; Resolve barriers to adherence; Track treatment response and progress; Navigate the health care system with patients; Educate patients & Engage patients in self-management; Relay information between patients and/or provider(s). The P.A.R.T.N.E.R. framework is the first to offer a checklist of care management functions that may promote successful collaboration with PCPs. Future research should examine the validity of this framework in various settings and for diverse patient populations affected by chronic diseases.

  3. Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary Gland Development and Function during Lactation.

    Science.gov (United States)

    Lee, Sooyeon; Hennigar, Stephen R; Alam, Samina; Nishida, Keigo; Kelleher, Shannon L

    2015-05-22

    The zinc transporter ZnT2 (SLC30A2) imports zinc into vesicles in secreting mammary epithelial cells (MECs) and is critical for zinc efflux into milk during lactation. Recent studies show that ZnT2 also imports zinc into mitochondria and is expressed in the non-lactating mammary gland and non-secreting MECs, highlighting the importance of ZnT2 in general mammary gland biology. In this study we used nulliparous and lactating ZnT2-null mice and characterized the consequences on mammary gland development, function during lactation, and milk composition. We found that ZnT2 was primarily expressed in MECs and to a limited extent in macrophages in the nulliparous mammary gland and loss of ZnT2 impaired mammary expansion during development. Secondly, we found that lactating ZnT2-null mice had substantial defects in mammary gland architecture and MEC function during secretion, including fewer, condensed and disorganized alveoli, impaired Stat5 activation, and unpolarized MECs. Loss of ZnT2 led to reduced milk volume and milk containing less protein, fat, and lactose compared with wild-type littermates, implicating ZnT2 in the regulation of mammary differentiation and optimal milk production during lactation. Together, these results demonstrate that ZnT2-mediated zinc transport is critical for mammary gland function, suggesting that defects in ZnT2 not only reduce milk zinc concentration but may compromise breast health and increase the risk for lactation insufficiency in lactating women. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. In-vitro inhibition of IFNγ+ iTreg mediated by monoclonal antibodies against cell surface determinants essential for iTreg function

    Directory of Open Access Journals (Sweden)

    Daniel Volker

    2012-08-01

    Full Text Available Abstract Background IFNγ-producing CD4+CD25+Foxp3+ PBL represent a subtype of iTreg that are associated with good long-term graft outcome in renal transplant recipients and suppress alloresponses in-vitro. To study the mechanism of immunosuppression, we attempted to block cell surface receptors and thereby inhibited the function of this iTreg subset in-vitro using monoclonal antibodies and recombinant proteins. Methods PBL of healthy control individuals were stimulated polyclonally in-vitro in the presence of monoclonal antibodies or recombinant proteins against/of CD178, CD152, CD279, CD28, CD95, and HLA-DR. Induction of IFNγ+ iTreg and proliferation of effector cells was determined using four-color fluorescence flow cytometry. Blockade of iTreg function was analyzed using polyclonally stimulated co-cultures with separated CD4+CD25+CD127-IFNγ+ PBL. Results High monoclonal antibody concentrations inhibited the induction of CD4+CD25+Foxp3+IFNγ+ PBL (anti-CD152, anti-CD279, anti-CD95: p +CD25+CD127-IFNγ+ PBL (anti-CD178, anti-CD152, anti-CD279, anti-CD95: p +CD25+Foxp3+IFNγ+ PBL (rCD152 and rCD95: p +CD25+CD127-IFNγ+ PBL showed lower cell proliferation than co-cultures with CD4+CD25+CD127-IFNγ- PBL (p +CD25+CD127-IFNγ- PBL-containing co-cultures in the presence of monoclonal antibody (anti-CD28, anti-CD152, anti-CD279: p +CD25+CD127-IFNγ+ PBL (with the exception anti-CD28 monoclonal antibody: p +CD25+CD127-IFNγ- PBL but do not efficiently block suppressive iTreg function in co-cultures with CD4+CD25+CD127-IFNγ+ PBL. Conclusions CD178, CD152, CD279, CD28, CD95, and HLA-DR determinants are important for induction and suppressive function of IFNγ+ iTreg.

  5. 23 CFR 661.19 - When is a bridge eligible for replacement?

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false When is a bridge eligible for replacement? 661.19... replacement? To be eligible for replacement, the bridge must be considered structurally deficient or functionally obsolete and must be in accordance with 23 CFR part 650.409(a) for bridge replacement. After an...

  6. The echocardiography of replacement heart valves

    Directory of Open Access Journals (Sweden)

    John B Chambers

    2016-10-01

    Full Text Available This is a practical description of how replacement valves are assessed using echocardiography. Normal transthoracic appearances including normal variants are described. The problem of differentiating normal function, patient–prosthesis mismatch and pathological obstruction in aortic replacement valves with high gradients is discussed. Obstruction and abnormal regurgitation is described for valves in the aortic, mitral and right-sided positions and when to use echocardiography in suspected infective endocarditis. The roles of transoesophageal and stress echocardiography are described and finally when other imaging techniques may be useful.

  7. The echocardiography of replacement heart valves.

    Science.gov (United States)

    Chambers, John B

    2016-09-01

    This is a practical description of how replacement valves are assessed using echocardiography. Normal transthoracic appearances including normal variants are described. The problem of differentiating normal function, patient-prosthesis mismatch and pathological obstruction in aortic replacement valves with high gradients is discussed. Obstruction and abnormal regurgitation is described for valves in the aortic, mitral and right-sided positions and when to use echocardiography in suspected infective endocarditis. The roles of transoesophageal and stress echocardiography are described and finally when other imaging techniques may be useful. © 2016 The authors.

  8. Signaling triggered by Thy-1 interaction with ß3 integrin on astrocytes is an essential step towards unraveling neuronal Thy-1 function

    Directory of Open Access Journals (Sweden)

    ANA MARIA AVALOS

    2002-01-01

    Full Text Available Thy-1 is an abundant neuronal glycoprotein in mammals. Despite such prevalence, Thy-1 function remains largely obscure in the absence of a defined ligand. Recently described evidence that Thy-1 interacts with ß3 integrin on astrocytes will be discussed. Thy-1 binding to ß3 integrin triggers tyrosine phosphorylation of focal adhesion proteins in astrocytes, thereby promoting focal adhesion formation, cell attachment and spreading. Thy-1 has been reported to modulate neurite outgrowth by triggering a cellular response in neurons. However, our data indicate that Thy-1 can also initiate signaling events that promote adhesion of adjacent astrocytes to the underlying surface. Preliminary results suggest that morphological changes observed in the actin cytoskeleton of astrocytes as a consequence of Thy-1 binding is mediated by small GTPases from the Rho family. Our findings argue that Thy-1 functions in a bimodal fashion, as a receptor on neuronal cells and as a ligand for ß3 integrin receptor on astrocytes. Since Thy-1 is implicated in the inhibition of neurite outgrowth, signaling events in astrocytes are likely to play an important role in this process

  9. Planar polarity pathway and Nance-Horan syndrome-like 1b have essential cell-autonomous functions in neuronal migration.

    Science.gov (United States)

    Walsh, Gregory S; Grant, Paul K; Morgan, John A; Moens, Cecilia B

    2011-07-01

    Components of the planar cell polarity (PCP) pathway are required for the caudal tangential migration of facial branchiomotor (FBM) neurons, but how PCP signaling regulates this migration is not understood. In a forward genetic screen, we identified a new gene, nhsl1b, required for FBM neuron migration. nhsl1b encodes a WAVE-homology domain-containing protein related to human Nance-Horan syndrome (NHS) protein and Drosophila GUK-holder (Gukh), which have been shown to interact with components of the WAVE regulatory complex that controls cytoskeletal dynamics and with the polarity protein Scribble, respectively. Nhsl1b localizes to FBM neuron membrane protrusions and interacts physically and genetically with Scrib to control FBM neuron migration. Using chimeric analysis, we show that FBM neurons have two modes of migration: one involving interactions between the neurons and their planar-polarized environment, and an alternative, collective mode involving interactions between the neurons themselves. We demonstrate that the first mode of migration requires the cell-autonomous functions of Nhsl1b and the PCP components Scrib and Vangl2 in addition to the non-autonomous functions of Scrib and Vangl2, which serve to polarize the epithelial cells in the environment of the migrating neurons. These results define a role for Nhsl1b as a neuronal effector of PCP signaling and indicate that proper FBM neuron migration is directly controlled by PCP signaling between the epithelium and the migrating neurons.

  10. The BEACH Domain Protein SPIRRIG Is Essential for Arabidopsis Salt Stress Tolerance and Functions as a Regulator of Transcript Stabilization and Localization.

    Directory of Open Access Journals (Sweden)

    Alexandra Steffens

    2015-07-01

    Full Text Available Members of the highly conserved class of BEACH domain containing proteins (BDCPs have been established as broad facilitators of protein-protein interactions and membrane dynamics in the context of human diseases like albinism, bleeding diathesis, impaired cellular immunity, cancer predisposition, and neurological dysfunctions. Also, the Arabidopsis thaliana BDCP SPIRRIG (SPI is important for membrane integrity, as spi mutants exhibit split vacuoles. In this work, we report a novel molecular function of the BDCP SPI in ribonucleoprotein particle formation. We show that SPI interacts with the P-body core component DECAPPING PROTEIN 1 (DCP1, associates to mRNA processing bodies (P-bodies, and regulates their assembly upon salt stress. The finding that spi mutants exhibit salt hypersensitivity suggests that the local function of SPI at P-bodies is of biological relevance. Transcriptome-wide analysis revealed qualitative differences in the salt stress-regulated transcriptional response of Col-0 and spi. We show that SPI regulates the salt stress-dependent post-transcriptional stabilization, cytoplasmic agglomeration, and localization to P-bodies of a subset of salt stress-regulated mRNAs. Finally, we show that the PH-BEACH domains of SPI and its human homolog FAN (Factor Associated with Neutral sphingomyelinase activation interact with DCP1 isoforms from plants, mammals, and yeast, suggesting the evolutionary conservation of an association of BDCPs and P-bodies.

  11. Influence of a Laser-Lok Surface on Immediate Functional Loading of Implants in Single-Tooth Replacement: Three-Year Results of a Prospective Randomized Clinical Study on Soft Tissue Response and Esthetics.

    Science.gov (United States)

    Guarnieri, Renzo; Grande, Maurizio; Ippoliti, Stefano; Iorio-Siciliano, Vincenzo; Riccitiello, Francesco; Farronato, Davide

    2015-01-01

    The purpose of the present prospective randomized study was to evaluate the influence of Laser-Lok microtextured surface on soft tissue peri-implant parameters and esthetics around immediate, functionally loaded implants for single-tooth replacement in the esthetic zone. This study included 77 patients divided into two groups based on different implants used: the control group had BioHorizons tapered internal non-Laser-Lok-type implants (NLL; n = 39) and the test group had BioHorizons tapered internal Laser-Lok-type implants (LL; n = 39). Outcome measures were survival, radiographic marginal bone-level changes, soft tissue parameters, and esthetics. One implant was lost in the test group and one in the control group, for a total survival rate of 96.1% after 3 years. Radiographically, mean crestal bone loss ± standard deviation was 0.59 ± 0.27 mm in the LL group compared with 1.17 ± 0.31 mm in the NLL group. A mean gain in papilla level of 0.41 ± 0.34 mm and 0.17 ± 0.36 mm was observed in the LL and the NLL groups, respectively, while the level of the midfacial peri-implant mucosa remained stable in both groups with no statistically significant differences (0.08 ± 0.42 mm for the LL group vs 0.06 ± 0.36 mm for the NLL group). The mean probing depth values in the LL and NLL groups were 0.58 ± 0.2 mm and 1.89 ± 0.3 mm, respectively. Within the limitations of this study, it was demonstrated that the clinical and esthetic outcome of immediate functional loading was more favorable for LL implants than for NLL implants.

  12. Iron replacement therapy

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Coskun, Mehmet; Weiss, Günter

    2016-01-01

    PURPOSE OF REVIEW: Approximately, one-third of the world's population suffers from anemia, and at least half of these cases are because of iron deficiency. With the introduction of new intravenous iron preparations over the last decade, uncertainty has arisen when these compounds should...... be administered and under which circumstances oral therapy is still an appropriate and effective treatment. RECENT FINDINGS: Numerous guidelines are available, but none go into detail about therapeutic start and end points or how iron-deficiency anemia should be best treated depending on the underlying cause...... of iron deficiency or in regard to concomitant underlying or additional diseases. SUMMARY: The study points to major issues to be considered in revisions of future guidelines for the true optimal iron replacement therapy, including how to assess the need for treatment, when to start and when to stop...

  13. Total ankle joint replacement.

    Science.gov (United States)

    2016-02-01

    Ankle arthritis results in a stiff and painful ankle and can be a major cause of disability. For people with end-stage ankle arthritis, arthrodesis (ankle fusion) is effective at reducing pain in the shorter term, but results in a fixed joint, and over time the loss of mobility places stress on other joints in the foot that may lead to arthritis, pain and dysfunction. Another option is to perform a total ankle joint replacement, with the aim of giving the patient a mobile and pain-free ankle. In this article we review the efficacy of this procedure, including how it compares to ankle arthrodesis, and consider the indications and complications. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  14. Electric circuits essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electric Circuits I includes units, notation, resistive circuits, experimental laws, transient circuits, network theorems, techniques of circuit analysis, sinusoidal analysis, polyph

  15. Business statistics I essentials

    CERN Document Server

    Clark, Louise

    2014-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Business Statistics I includes descriptive statistics, introduction to probability, probability distributions, sampling and sampling distributions, interval estimation, and hypothesis t

  16. Heat transfer II essentials

    CERN Document Server

    REA, The Editors of

    1988-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Heat Transfer II reviews correlations for forced convection, free convection, heat exchangers, radiation heat transfer, and boiling and condensation.

  17. Statistics I essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Statistics I covers include frequency distributions, numerical methods of describing data, measures of variability, parameters of distributions, probability theory, and distributions.

  18. Computer science I essentials

    CERN Document Server

    Raus, Randall

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Computer Science I includes fundamental computer concepts, number representations, Boolean algebra, switching circuits, and computer architecture.

  19. Modern algebra essentials

    CERN Document Server

    Lutfiyya, Lutfi A

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Modern Algebra includes set theory, operations, relations, basic properties of the integers, group theory, and ring theory.

  20. Differential equations I essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Differential Equations I covers first- and second-order equations, series solutions, higher-order linear equations, and the Laplace transform.

  1. Algebra & trigonometry II essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Algebra & Trigonometry II includes logarithms, sequences and series, permutations, combinations and probability, vectors, matrices, determinants and systems of equations, mathematica

  2. Transport phenomena II essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Transport Phenomena II covers forced convention, temperature distribution, free convection, diffusitivity and the mechanism of mass transfer, convective mass transfer, concentration

  3. Numerical analysis II essentials

    CERN Document Server

    REA, The Editors of; Staff of Research Education Association

    1989-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Numerical Analysis II covers simultaneous linear systems and matrix methods, differential equations, Fourier transformations, partial differential equations, and Monte Carlo methods.

  4. Efficient four fragment cloning for the construction of vectors for targeted gene replacement in filamentous fungi

    Directory of Open Access Journals (Sweden)

    Kristensen Matilde B

    2008-08-01

    Full Text Available Abstract Background The rapid increase in whole genome fungal sequence information allows large scale functional analyses of target genes. Efficient transformation methods to obtain site-directed gene replacement, targeted over-expression by promoter replacement, in-frame epitope tagging or fusion of coding sequences with fluorescent markers such as GFP are essential for this process. Construction of vectors for these experiments depends on the directional cloning of two homologous recombination sequences on each side of a selection marker gene. Results Here, we present a USER Friendly cloning based technique that allows single step cloning of the two required homologous recombination sequences into different sites of a recipient vector. The advantages are: A simple experimental design, free choice of target sequence, few procedures and user convenience. The vectors are intented for Agrobacterium tumefaciens and protoplast based transformation technologies. The system has been tested by the construction of vectors for targeted replacement of 17 genes and overexpression of 12 genes in Fusarium graminearum. The results show that four fragment vectors can be constructed in a single cloning step with an average efficiency of 84% for gene replacement and 80% for targeted overexpression. Conclusion The new vectors designed for USER Friendly cloning provided a fast reliable method to construct vectors for targeted gene manipulations in fungi.

  5. Functional transforming growth factor-β receptor type II expression by CD4+ T cells in Peyer's patches is essential for oral tolerance induction.

    Directory of Open Access Journals (Sweden)

    Rebekah S Gilbert

    Full Text Available Our previous studies have shown that Peyer's patches (PPs play a key role in the induction of oral tolerance. Therefore, we hypothesized that PPs are an important site for Transforming Growth Factor (TGF-β signaling and sought to prove that this tissue is of importance in oral tolerance induction. We found that expression of TGF-β type II receptor (TGFβRII by CD4(+ T cells increases and persists in the PPs of normal C57BL/6 mice after either high- or low-dose feeding of OVA when compared to mesenteric lymph nodes (MLNs and spleen. Approximately one-third of these TGFβRII(+ CD4(+ T cells express the transcription factor Foxp3. Interestingly, the number of TGFβRII(+ CD4(+ T cells in PPs decreased when OVA-fed mice were orally challenged with OVA plus native cholera toxin (CT. In contrast, numbers of TGFβRII(+ CD4(+ T cells were increased in the intestinal lamina propria (iLP of these challenged mice. Further, these PP CD4(+ TGFβRII(+ T cells upregulated Foxp3 within 2 hours after OVA plus CT challenge. Mice fed PBS and challenged with OVA plus CT did not reveal any changes in TGFβRII expression by CD4(+ T cells. In order to test the functional property of TGFβRII in the induction of oral tolerance, CD4dnTGFβRII transgenic mice, in which TGFβRII signaling is abrogated from all CD4(+ T cells, were employed. Importantly, these mice could not develop oral tolerance to OVA. Our studies show a critical, dose-independent, role for TGFβRII expression and function by CD4(+ T cells in the gut-associated lymphoid tissues, further underlining the vital role of PPs in oral tolerance.

  6. Systematic deletion analyses of the fla genes in the flagella operon identify several genes essential for proper assembly and function of flagella in the archaeon, Methanococcus maripaludis.

    Science.gov (United States)

    Chaban, Bonnie; Ng, Sandy Y M; Kanbe, Masaomi; Saltzman, Ilana; Nimmo, Graeme; Aizawa, Shin-Ichi; Jarrell, Ken F

    2007-11-01

    The archaeal flagellum is a unique motility apparatus in the prokaryotic domain, distinct from the bacterial flagellum. Most of the currently recognized archaeal flagella-associated genes fall into a single fla operon that contains the genes for the flagellin proteins (two or more genes designated as flaA or flaB), some variation of a set of conserved proteins of unknown function (flaC, flaD, flaE, flaF, flaG and flaH), an ATPase (flaI) and a membrane protein (flaJ). In addition, the flaD gene has been demonstrated to encode two proteins: a full-length gene product and a truncated product derived from an alternate, internal start site. A systematic deletion approach was taken using the methanogen Methanococcus maripaludis to investigate the requirement and a possible role for these proposed flagella-associated genes. Markerless in-frame deletion strains were created for most of the genes in the M. maripaludis fla operon. In addition, a strain lacking the truncated FlaD protein [FlaD M(191)I] was also created. DNA sequencing and Southern blot analysis confirmed each mutant strain, and the integrity of the remaining operon was confirmed by immunoblot. With the exception of the DeltaFlaB3 and FlaD M(191)I strains, all mutants were non-motile by light microscopy and non-flagellated by electron microscopy. A detailed examination of the DeltaFlaB3 mutant flagella revealed that these structures had no hook region, while the FlaD M(191)I strain appeared identical to wild type. Each deletion strain was complemented, and motility and flagellation was restored. Collectively, these results demonstrate for first time that these fla operon genes are directly involved and critically required for proper archaeal flagella assembly and function.

  7. Phaser.MRage: automated molecular replacement

    International Nuclear Information System (INIS)

    Bunkóczi, Gábor; Echols, Nathaniel; McCoy, Airlie J.; Oeffner, Robert D.; Adams, Paul D.; Read, Randy J.

    2013-01-01

    The functionality of the molecular-replacement pipeline phaser.MRage is introduced and illustrated with examples. Phaser.MRage is a molecular-replacement automation framework that implements a full model-generation workflow and provides several layers of model exploration to the user. It is designed to handle a large number of models and can distribute calculations efficiently onto parallel hardware. In addition, phaser.MRage can identify correct solutions and use this information to accelerate the search. Firstly, it can quickly score all alternative models of a component once a correct solution has been found. Secondly, it can perform extensive analysis of identified solutions to find protein assemblies and can employ assembled models for subsequent searches. Thirdly, it is able to use a priori assembly information (derived from, for example, homologues) to speculatively place and score molecules, thereby customizing the search procedure to a certain class of protein molecule (for example, antibodies) and incorporating additional biological information into molecular replacement

  8. Efectos de la terapia de reemplazo hormonal sobre la función autonómica en mujeres postmenopáusicas Effects of estrogen replacement therapy on autonomic function of post-menopausal women

    Directory of Open Access Journals (Sweden)

    Juan C Guzmán

    2007-02-01

    para mejorar los síntomas de la menopausia durante un tiempo corto, principalmente en mujeres postmenopáusicas jóvenes no hipertensas.Background: estrogen deficit during menopause may be related to cardiac autonomic function imbalance, reducing the cardiovagal reflex response that could potentially increase cardiovascular risk. The physiological mechanisms that lead to this alteration in postmenopausal women remain unclear. In this article, the effect of hormonal replacement therapy on autonomic function in women submitted to hysterectomy is discussed. Methods: Fifty women with a previous hysterectomy and amenorrhea for 1 year prior to surgery were enrolled in a prospective randomized crossover double-blind placebo controlled trial. Either oral estrogen replacement therapy (ERT conjugated estrogens 0.625 mg once a day or placebo, were randomly administered in a crossover design during 12 weeks with a 2 week washout period. Cardiovagal autonomic function was assessed by conventional techniques and through venous occlusion plethysmography in order to evaluate vascular autonomic function calculating forearm blood flow (FBF and peripheral vascular resistance (PVR at baseline, and during head-up tilt (HUT and a non-hypotensive stimuli (-10mmHg lower-body negative pressure (LBNP. Results: No differences were found in cardiovagal autonomic function comparing ERT vs. placebo at baseline resting conditions, nor during HUT and LBNP. A significant difference was identified in supine FBF [1.9(0.5 vs. 1.5(0.5, p=0.02] as well as in PVR [53.5(18.2 vs. 68.6(34, p=0.02] comparing ERT vs. placebo interventions. Conclusions: Short term ERT did not improve cardiovascular autonomic reflex responses in postmenopausal women, but increased vascular relaxation primarily by reducing peripheral vascular resistance. Hormone replacement therapy can be used under adequate supervision in order to improve menopausal symptoms during a short period of time, mainly in young non-hypertensive post

  9. Essential Control of the Function of the Striatopallidal Neuron by Pre-coupled Complexes of Adenosine A2A-Dopamine D2 Receptor Heterotetramers and Adenylyl Cyclase

    Directory of Open Access Journals (Sweden)

    Sergi Ferré

    2018-04-01

    Full Text Available The central adenosine system and adenosine receptors play a fundamental role in the modulation of dopaminergic neurotransmission. This is mostly achieved by the strategic co-localization of different adenosine and dopamine receptor subtypes in the two populations of striatal efferent neurons, striatonigral and striatopallidal, that give rise to the direct and indirect striatal efferent pathways, respectively. With optogenetic techniques it has been possible to dissect a differential role of the direct and indirect pathways in mediating “Go” responses upon exposure to reward-related stimuli and “NoGo” responses upon exposure to non-rewarded or aversive-related stimuli, respectively, which depends on their different connecting output structures and their differential expression of dopamine and adenosine receptor subtypes. The striatopallidal neuron selectively expresses dopamine D2 receptors (D2R and adenosine A2A receptors (A2AR, and numerous experiments using multiple genetic and pharmacological in vitro, in situ and in vivo approaches, demonstrate they can form A2AR-D2R heteromers. It was initially assumed that different pharmacological interactions between dopamine and adenosine receptor ligands indicated the existence of different subpopulations of A2AR and D2R in the striatopallidal neuron. However, as elaborated in the present essay, most evidence now indicates that all interactions can be explained with a predominant population of striatal A2AR-D2R heteromers forming complexes with adenylyl cyclase subtype 5 (AC5. The A2AR-D2R heteromer has a tetrameric structure, with two homodimers, which allows not only multiple allosteric interactions between different orthosteric ligands, agonists, and antagonists, but also the canonical Gs-Gi antagonistic interaction at the level of AC5. We present a model of the function of the A2AR-D2R heterotetramer-AC5 complex, which acts as an integrative device of adenosine and dopamine signals that

  10. LARP1 functions as a molecular switch for mTORC1-mediated translation of an essential class of mRNAs.

    Science.gov (United States)

    Hong, Sungki; Freeberg, Mallory A; Han, Ting; Kamath, Avani; Yao, Yao; Fukuda, Tomoko; Suzuki, Tsukasa; Kim, John K; Inoki, Ken

    2017-06-26

    The RNA binding protein, LARP1, has been proposed to function downstream of mTORC1 to regulate the translation of 5'TOP mRNAs such as those encoding ribosome proteins (RP). However, the roles of LARP1 in the translation of 5'TOP mRNAs are controversial and its regulatory roles in mTORC1-mediated translation remain unclear. Here we show that LARP1 is a direct substrate of mTORC1 and Akt/S6K1. Deep sequencing of LARP1-bound mRNAs reveal that non-phosphorylated LARP1 interacts with both 5' and 3'UTRs of RP mRNAs and inhibits their translation. Importantly, phosphorylation of LARP1 by mTORC1 and Akt/S6K1 dissociates it from 5'UTRs and relieves its inhibitory activity on RP mRNA translation. Concomitantly, phosphorylated LARP1 scaffolds mTORC1 on the 3'UTRs of translationally-competent RP mRNAs to facilitate mTORC1-dependent induction of translation initiation. Thus, in response to cellular mTOR activity, LARP1 serves as a phosphorylation-sensitive molecular switch for turning off or on RP mRNA translation and subsequent ribosome biogenesis.

  11. Replacing carbohydrate during a glucose challenge with the egg white portion or whole eggs protects against postprandial impairments in vascular endothelial function in prediabetic men by limiting increases in glycaemia and lipid peroxidation.

    Science.gov (United States)

    McDonald, Joshua D; Chitchumroonchokchai, Chureeporn; Li, Jinhui; Mah, Eunice; Labyk, Allison N; Reverri, Elizabeth J; Ballard, Kevin D; Volek, Jeff S; Bruno, Richard S

    2018-02-01

    Eggs attenuate postprandial hyperglycaemia (PPH), which transiently impairs vascular endothelial function (VEF). We hypothesised that co-ingestion of a glucose challenge with egg-based meals would protect against glucose-induced impairments in VEF by attenuating PPH and oxidative stress. A randomised, cross-over study was conducted in prediabetic men (n 20) who ingested isoenegertic meals (1674 kJ (400 kcal)) containing 100 g glucose (GLU), or 75 g glucose with 1·5 whole eggs (EGG), seven egg whites (WHITE) or two egg yolks (YOLK). At 30 min intervals for 3 h, brachial artery flow-mediated dilation (FMD), plasma glucose, insulin, cholecystokinin (CCK), lipids (total, LDL- and HDL-cholesterol; TAG), F2-isoprostanes normalised to arachidonic acid (F2-IsoPs/AA), and methylglyoxal were assessed. In GLU, FMD decreased at 30-60 min and returned to baseline levels by 90 min. GLU-mediated decreases in FMD were attenuated at 30-60 min in EGG and WHITE. Compared with GLU, FMDAUC was higher in EGG and WHITE only. Relative to baseline, glucose increased at 30-120 min in GLU and YOLK but only at 30-90 min in EGG and WHITE. GlucoseAUC and insulinAUC were also lower in EGG and WHITE only. However, CCKAUC was higher in EGG and WHITE compared with GLU. Compared with GLU, F2-IsoPs/AAAUC was lower in EGG and WHITE but unaffected by YOLK. Postprandial lipids and methylglyoxal did not differ between treatments. Thus, replacing a portion of a glucose challenge with whole eggs or egg whites, but not yolks, limits postprandial impairments in VEF by attenuating increases in glycaemia and lipid peroxidation.

  12. COMO: a program for combined molecular replacement.

    Science.gov (United States)

    Jogl, G; Tao, X; Xu, Y; Tong, L

    2001-08-01

    The combined molecular-replacement protocol uses a limited six-dimensional search to solve a structure by the molecular-replacement method, with the sampling of the rotational degrees of freedom guided by the rotation function. This protocol therefore automatically combines the information on the rotational and translational parameters of the search model. The combined molecular-replacement protocol has been implemented in a new computer program, COMO. The calculation of the Patterson correlation translation function has been optimized to improve its speed performance. A packing check is implemented that automatically removes impossible solutions and thereby increases the signal in the calculation. A family of atomic models can be used as the search model; the program will automatically select the model that gives the best result. The command interface is well organized and requires the definition of only a few critical parameters by the user. In addition, a graphical user interface has been constructed for the program. The program has been used to solve several difficult molecular-replacement problems. A case is presented where the program automatically determined the orientation and position of five copies of a search model in a high-symmetry space group.

  13. Solid-State Thyratron Replacement. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Roth, Ian [Diversified Technologies, Inc., Bedford, MA

    2017-12-12

    Under this SBIR, DTI developed a solid-state switch as an alternative to legacy thyratron equipment. Our Phase II objective was to make a solid-state thyratron replacement that would provide equivalent or better performance, much higher reliability (at least a 20 year lifetime, compared to a thyratron’s two-year lifetime) and would sell for ~3x the cost of a thyratron, or less than $40k. We were successful in building a solid-state switch which could reliably function as a thyratron replacement. The unit was designed to directly replace the thyratrons currently being used at SLAC’s Linac Coherent Light Source (LCLS), and was built in a tank that was small enough to fit into the existing thyratron cabinet, providing a true form-fit-function replacement path. We tested the switch at the full operating specifications: 48 kV, 6.3 kA, and 1 µs risetime. We also demonstrated a peak-to-peak pulse jitter of 1.5 ns, which is five times shorter than is typical for thyratrons. This lower jitter would improve the performance of the LCLS beam. The predicted reliability is more than 80 years, which is 40 times greater than a thyratron.

  14. Semantic Factors Predict the Rate of Lexical Replacement of Content Words

    OpenAIRE

    Vejdemo, Susanne; H?rberg, Thomas

    2016-01-01

    The rate of lexical replacement estimates the diachronic stability of word forms on the basis of how frequently a proto-language word is replaced or retained in its daughter languages. Lexical replacement rate has been shown to be highly related to word class and word frequency. In this paper, we argue that content words and function words behave differently with respect to lexical replacement rate, and we show that semantic factors predict the lexical replacement rate of content words. For t...

  15. Joint replacement in Zambia: A review of Hip & Knee Replacement ...

    African Journals Online (AJOL)

    Background: Incidence of major joint replacement surgery is on the rise in Africa but this trend has not been matched by proper audits in the form of National Joint Registries. Objective: This paper presents the short-term findings from a joint replacement register started at the Zambian-Italian Orthopaedic Hospital (ZIOH) in ...

  16. CALiPER Exploratory Study Retail Replacement Lamps – 2011

    Energy Technology Data Exchange (ETDEWEB)

    None

    2012-04-02

    In 2010, CALiPER conducted a study on LED replacement lamps found in retail stores. The results were less than satisfactory, and many products were classified as being unlikely to meet consumer expectations. In November 2011, CALiPER purchased a new sample of products for a follow-up study, with the intent of characterizing the progress of this essential market segment.

  17. Electronics I essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electronics I covers fundamentals of semiconductor devices, junction diodes, bipolar junction transistors, power supplies, multitransistor circuits, small signals, low-frequency anal

  18. Electronics II essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electronics II covers operational amplifiers, feedback and frequency compensation of OP amps, multivibrators, logic gates and families, Boolean algebra, registers, counters, arithmet

  19. Boolean algebra essentials

    CERN Document Server

    Solomon, Alan D

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Boolean Algebra includes set theory, sentential calculus, fundamental ideas of Boolean algebras, lattices, rings and Boolean algebras, the structure of a Boolean algebra, and Boolean

  20. Group theory I essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Group Theory I includes sets and mapping, groupoids and semi-groups, groups, isomorphisms and homomorphisms, cyclic groups, the Sylow theorems, and finite p-groups.