Science.gov

Sample records for leone age-dependent haplotype

  1. Is extinction age dependent?

    USGS Publications Warehouse

    Doran, N.A.; Arnold, A.J.; Parker, W.C.; Huffer, F.W.

    2006-01-01

    Age-dependent extinction is an observation with important biological implications. Van Valen's Red Queen hypothesis triggered three decades of research testing its primary implication: that age is independent of extinction. In contrast to this, later studies with species-level data have indicated the possible presence of age dependence. Since the formulation of the Red Queen hypothesis, more powerful tests of survivorship models have been developed. This is the first report of the application of the Cox Proportional Hazards model to paleontological data. Planktonic foraminiferal morphospecies allow the taxonomic and precise stratigraphic resolution necessary for the Cox model. As a whole, planktonic foraminiferal morphospecies clearly show age-dependent extinction. In particular, the effect is attributable to the presence of shorter-ranged species (range < 4 myr) following extinction events. These shorter-ranged species also possess tests with unique morphological architecture. The morphological differences are probably epiphenomena of underlying developmental and heterochronic processes of shorter-ranged species that survived various extinction events. Extinction survivors carry developmental and morphological characteristics into postextinction recovery times, and this sets them apart from species populations established independently of extinction events. Copyright ?? 2006, SEPM (Society for Sedimentary Geology).

  2. Haplotyping algorithms

    SciTech Connect

    Sobel, E.; Lange, K.; O`Connell, J.R.

    1996-12-31

    Haplotyping is the logical process of inferring gene flow in a pedigree based on phenotyping results at a small number of genetic loci. This paper formalizes the haplotyping problem and suggests four algorithms for haplotype reconstruction. These algorithms range from exhaustive enumeration of all haplotype vectors to combinatorial optimization by simulated annealing. Application of the algorithms to published genetic analyses shows that manual haplotyping is often erroneous. Haplotyping is employed in screening pedigrees for phenotyping errors and in positional cloning of disease genes from conserved haplotypes in population isolates. 26 refs., 6 figs., 3 tabs.

  3. Country Profiles, Sierra Leone.

    ERIC Educational Resources Information Center

    Dow, Thomas E., Jr.

    A profile of Sierra Leone is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population (size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, migration,…

  4. Detecting local haplotype sharing and haplotype association

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel haplotype association method is presented, and its power is demonstrated. Relying on a statistical model for linkage disequilibrium (LD), the method first infers ancestral haplotypes and their loadings at each marker for each individual. The loadings are then used to quantify local haplotype...

  5. Fighting Ebola in Sierra Leone.

    PubMed

    Clavagnier, Isabelle

    2015-01-01

    Sophie and Pierre have enrolled in the operational team of a humanitarian organisation for two months, in order to help contain the Ebola epidemic. They landed in Freetown, the capital of Sierra Leone, only yesterday. PMID:26146002

  6. Detecting local haplotype sharing and haplotype association.

    PubMed

    Xu, Hanli; Guan, Yongtao

    2014-07-01

    A novel haplotype association method is presented, and its power is demonstrated. Relying on a statistical model for linkage disequilibrium (LD), the method first infers ancestral haplotypes and their loadings at each marker for each individual. The loadings are then used to quantify local haplotype sharing between individuals at each marker. A statistical model was developed to link the local haplotype sharing and phenotypes to test for association. We devised a novel method to fit the LD model, reducing the complexity from putatively quadratic to linear (in the number of ancestral haplotypes). Therefore, the LD model can be fitted to all study samples simultaneously, and, consequently, our method is applicable to big data sets. Compared to existing haplotype association methods, our method integrated out phase uncertainty, avoided arbitrariness in specifying haplotypes, and had the same number of tests as the single-SNP analysis. We applied our method to data from the Wellcome Trust Case Control Consortium and discovered eight novel associations between seven gene regions and five disease phenotypes. Among these, GRIK4, which encodes a protein that belongs to the glutamate-gated ionic channel family, is strongly associated with both coronary artery disease and rheumatoid arthritis. A software package implementing methods described in this article is freely available at http://www.haplotype.org. PMID:24812308

  7. Mitochondrial DNA genetic diversity among four ethnic groups in Sierra Leone.

    PubMed

    Jackson, Bruce A; Wilson, Jamie Lee; Kirbah, Salwa; Sidney, Sheree S; Rosenberger, Joshua; Bassie, Larry; Alie, Joe A D; McLean, David C; Garvey, W Timothy; Ely, Bert

    2005-09-01

    Although there are numerous ethnic groups in Sierra Leone, the Mende and Temne together account for approximately 60% of the total population. To see if genetic differences could be observed among ethnic groups in Sierra Leone, the nucleotide sequence of the hypervariable 1 (HV1) region of mitochondrial DNA (mtDNA) was determined from samples of the two major ethnic groups, the Mende (n=59) and Temne (n=121), and of two minor ethnic groups, the Loko (n=29) and Limba (n=67). Among these 276 HV1 sequences, 164 individual haplotypes were observed. An analysis of molecular variance indicated that the distribution of these haplotypes within the Limba sample was significantly different from that of the other ethnic groups. No significant genetic variation was seen between the Mende, Temne, and Loko. These results indicate that distinguishing genetic differences can be observed among ethnic groups residing in historically close proximity to one another. Furthermore, we observed some mitochondrial DNA haplotypes that are common among the Sierra Leone ethnic groups but that have not been observed in other published studies of West African ethnic groups. Therefore, we may have evidence for mtDNA lineages that are unique to this region of West Africa. PMID:15761855

  8. SEECAL: Program to calculate age-dependent

    SciTech Connect

    Cristy, M.; Eckerman, K.F.

    1993-12-01

    This report describes the computer program SEECAL, which calculates specific effective energies (SEE) to specified target regions for ages newborn, 1 y, 5 y, 10 y, 15 y, a 70-kg adult male, and a 58-kg adult female. The dosimetric methodology is that of the International Commission on Radiological Protection (ICRP) and is generally consistent with the schema of the Medical Internal Radiation Dose committee of the US Society of Nuclear Medicine. Computation of SEEs is necessary in the computation of equivalent dose rate in a target region, for occupational or public exposure to radionuclides taken into the body. Program SEECAL replaces the program SEE that was previously used by the Dosimetry Research Group at Oak Ridge National Laboratory. The program SEE was used in the dosimetric calculations for occupational exposures for ICRP Publication 30 and is limited to adults. SEECAL was used to generate age-dependent SEEs for ICRP Publication 56, Part 1. SEECAL is also incorporated into DCAL, a radiation dose and risk calculational system being developed for the Environmental Protection Agency. Electronic copies of the program and data files and this report are available from the Radiation Shielding Information Center at Oak Ridge National Laboratory.

  9. Age-dependent decay in the landscape

    SciTech Connect

    Winitzki, Sergei

    2008-03-15

    The picture of the 'multiverse' arising in diverse cosmological scenarios involves transitions between metastable vacuum states. It was pointed out by Krauss and Dent that the transition rates decrease at very late times, leading to a dependence of the transition probability between vacua on the age of each vacuum region. I investigate the implications of this non-Markovian, age-dependent decay on the global structure of the spacetime in landscape scenarios. I show that the fractal dimension of the eternally inflating domain is precisely equal to 3, instead of being slightly below 3, which is the case in scenarios with purely Markovian, age-independent decay. I develop a complete description of a non-Markovian landscape in terms of a nonlocal master equation. Using this description I demonstrate by an explicit calculation that, under some technical assumptions about the landscape, the probabilistic predictions of our position in the landscape are essentially unchanged, regardless of the measure used to extract these predictions. I briefly discuss the physical plausibility of realizing non-Markovian vacuum decay in cosmology in view of the possible decoherence of the metastable quantum state.

  10. Human serum metabolic profiles are age dependent.

    PubMed

    Yu, Zhonghao; Zhai, Guangju; Singmann, Paula; He, Ying; Xu, Tao; Prehn, Cornelia; Römisch-Margl, Werner; Lattka, Eva; Gieger, Christian; Soranzo, Nicole; Heinrich, Joachim; Standl, Marie; Thiering, Elisabeth; Mittelstraß, Kirstin; Wichmann, Heinz-Erich; Peters, Annette; Suhre, Karsten; Li, Yixue; Adamski, Jerzy; Spector, Tim D; Illig, Thomas; Wang-Sattler, Rui

    2012-12-01

    Understanding the complexity of aging is of utmost importance. This can now be addressed by the novel and powerful approach of metabolomics. However, to date, only a few metabolic studies based on large samples are available. Here, we provide novel and specific information on age-related metabolite concentration changes in human homeostasis. We report results from two population-based studies: the KORA F4 study from Germany as a discovery cohort, with 1038 female and 1124 male participants (32-81 years), and the TwinsUK study as replication, with 724 female participants. Targeted metabolomics of fasting serum samples quantified 131 metabolites by FIA-MS/MS. Among these, 71/34 metabolites were significantly associated with age in women/men (BMI adjusted). We further identified a set of 13 independent metabolites in women (with P values ranging from 4.6 × 10(-04) to 7.8 × 10(-42) , α(corr) = 0.004). Eleven of these 13 metabolites were replicated in the TwinsUK study, including seven metabolite concentrations that increased with age (C0, C10:1, C12:1, C18:1, SM C16:1, SM C18:1, and PC aa C28:1), while histidine decreased. These results indicate that metabolic profiles are age dependent and might reflect different aging processes, such as incomplete mitochondrial fatty acid oxidation. The use of metabolomics will increase our understanding of aging networks and may lead to discoveries that help enhance healthy aging. PMID:22834969

  11. Susu Language Manual: Sierra Leone.

    ERIC Educational Resources Information Center

    Peace Corps, Freetown (Sierra Leone).

    A teacher's guide for Susu is designed for Peace Corps volunteer language instruction and geared to the daily language needs of volunteers in Sierra Leone. It contains a section on Susu phonology and 28 lessons on these topics: situation-specific greetings, basic greetings, introducing a friend, the market, travel and getting directions, visiting…

  12. English Teaching Profile: Sierra Leone.

    ERIC Educational Resources Information Center

    British Council, London (England). English Language and Literature Div.

    The role and status of English in Sierra Leone are examined, with attention directed to: (1) English within the education system, (2) teachers of English, (3) materials support; (4) educational administration for English teaching, (5) development and planning, (6) British support for the teaching of English, and (7) commercial opportunities.…

  13. Sierra Leone Temne Language Manual.

    ERIC Educational Resources Information Center

    Peace Corps, Washington, DC.

    A language guide to Temne is designed for Peace Corps volunteers serving in Sierra Leone. It contains introductory sections about the Temnes and Temne phonology and orthography, teacher notes on the use of the manual, and 12 lessons. Each lesson consists of a dialogue or narrative, notes on classroom presentation, vocabulary and useful phrases,…

  14. English Teaching Profile: Sierra Leone.

    ERIC Educational Resources Information Center

    British Council, London (England). English Language and Literature Div.

    This review of the status of English language instruction in Sierra Leone provides an overview of the role of English in the society in general and outlines the status of English use and instruction in the educational system at all levels (preprimary, elementary, secondary, higher, vocational, adult, and teacher education). Topics covered are: the…

  15. My Great Migration from Sierra Leone

    ERIC Educational Resources Information Center

    Harvard Educational Review, 2011

    2011-01-01

    This article presents the author's personal narrative as an immigrant from Sierra Leone who has undergone so many challenges in life and ended up turning all these obstacles into opportunities. In this article, the author describes his life growing up in Sierra Leone, his first experience of the horrors of war, his life as a student, and his dream…

  16. Paederus dermatitis in Sierra Leone.

    PubMed

    Qadir, Syed Nurul Rasool; Raza, Naeem; Rahman, Simeen Ber

    2006-01-01

    Paederus dermatitis, a type of irritant contact dermatitis attributed to a Staphylinid beetle, is prevalent in most parts of the world. We studied 50 cases of Paederus dermatitis at the United Nations Hospital at Koidu Sierra Leone (West Africa), over a period of 6 months from Oct 2003 to Mar 2004. The objectives of the study were to determine clinical patterns of dermatitis and its response to topical steroids, with and without antibiotics. Patients with a definite history of contact with the insect were included in the study. Amongst these, 14 of the more severe cases were treated with oral prednisolone or intralesional triamcinolone acetonide. The remainder of the 36 patients were divided in two equal groups A and B. Patients in Group A were treated with topical diflucortolone valerate 0.001 percent and oral cetirizine hydrochloride; patients in group B were given oral ciprofloxacin in addition. In 50 patients studied, 43 (86%) were males and 7 (14%) were females. The neck was the most common site involved followed by face. Healing time ranged from 14 to 28 days and lesions in all the patients healed with residual dyschromia. Healing time was shorter in Group B patients in comparison with those in Group A. Paederus dermatitis in Sierra Leone is a relatively severe form of this dermatitis. The better response to a combination of topical steroids and oral antibiotics may indicate concurrent bacterial infection. PMID:17459295

  17. Quantifying Age-dependent Extinction from Species Phylogenies.

    PubMed

    Alexander, Helen K; Lambert, Amaury; Stadler, Tanja

    2016-01-01

    Several ecological factors that could play into species extinction are expected to correlate with species age, i.e., time elapsed since the species arose by speciation. To date, however, statistical tools to incorporate species age into likelihood-based phylogenetic inference have been lacking. We present here a computational framework to quantify age-dependent extinction through maximum likelihood parameter estimation based on phylogenetic trees, assuming species lifetimes are gamma distributed. Testing on simulated trees shows that neglecting age dependence can lead to biased estimates of key macroevolutionary parameters. We then apply this method to two real data sets, namely a complete phylogeny of birds (class Aves) and a clade of self-compatible and -incompatible nightshades (Solanaceae), gaining initial insights into the extent to which age-dependent extinction may help explain macroevolutionary patterns. Our methods have been added to the R package TreePar. PMID:26405218

  18. AGE-DEPENDENT CHANGES IN ACTIVITY OF MALLARD PLASMA CHOLINESTERASES

    EPA Science Inventory

    Plasma acetylcholinesterase (AChE) and butrylcholinesterase (BChE) activity was measured repeatedly in 27 mallard (Anas platyrhynchos) ducklings between 7 and 85 days of age to determine age-dependent changes in enzyme activity. Plasma AChE, BChe, and total cholinesterase (ChE) a...

  19. Leon Knopoff (1926-2011)

    NASA Astrophysics Data System (ADS)

    Davis, Paul; Jackson, David; Gilbert, Freeman

    2011-06-01

    Leon Knopoff died at his home in Sherman Oaks, Calif., on 20 January 2011 at the age of 85. A man of wide-ranging talents, he had the rare distinction of being simultaneously a professor of physics, a professor of geophysics, and a research musicologist at the University of California, Los Angeles (UCLA). As an undergraduate he studied electrical engineering and obtained his Ph.D. in physics and mathematics at the California Institute of Technology (Caltech) in 1949. He was recruited to the Institute of Geophysics (now the Institute of Geophysics and Planetary Physics) at UCLA in 1950 by Louis Slichter, where he became a professor of geophysics in 1957 and of geophysics and physics in 1961. He became a research musicologist in the UCLA Institute of Ethnomusicology soon after it was formed in 1960. Other appointments included faculty positions at Miami University in Ohio (1948-1950) and Caltech (1962-1963) and visiting appointments at Cambridge, Karlsruhe, Harvard, Santiago, Trieste, and Venice.

  20. Age-dependent protection quantities for external photon irradiation.

    PubMed

    Chou, D P; Wang, J N; Chen, I J

    2001-01-01

    The age-dependent conversion coefficients of the protection quantities, the equivalent dose and the effective dose defined by the International Commission on Radiological Protection (ICRP), are obtained. A Monte Carlo computer code and the age-dependent hermaphrodite mathematical phantoms of six age groups: newborn, 1, 5, 10, 15 years old and adult are used for the evaluation. Twenty-three photon source energies from 10 keV to 10 MeV and six kinds of irradiation geometries: AP, PA, RLAT, LLAT, ROT, and ISO are chosen in the calculation. The evaluated conversion coefficients for the adult are compared with those in ICRP Publication 74 with good agreement. The conversion coefficients of the equivalent dose and the effective dose increase while the age of the phantom decreases, but with some exceptions for the AP irradiation geometry under certain conditions. PMID:11605795

  1. A SIRS epidemic model with infection-age dependence

    NASA Astrophysics Data System (ADS)

    Zhang, Zhonghua; Peng, Jigen

    2007-07-01

    Based on J. Mena-Lorca and H.W. Hethcote's epidemic model, a SIRS epidemic model with infection-age-dependent infectivity and general nonlinear contact rate is formulated. Under general conditions, the unique existence of its global positive solutions is obtained. Moreover, under more general assumptions than the existing, the existence and asymptotical stability of its equilibria are discussed. In the end, the condition on the stability of endemic equilibrium is verified by a special model.

  2. Age-dependent diet choice in an avian top predator.

    PubMed

    Rutz, Christian; Whittingham, Mark J; Newton, Ian

    2006-03-01

    Age-dependent breeding performance is arguably one of the best-documented phenomena in ornithology. The existence of age-related trends has major implications for life-history theory, but the proximate reasons for these patterns remain poorly understood. It has been proposed that poor breeding performance of young individuals might reflect lack of foraging skills. We investigated this possibility in a medium-sized, powerful raptor-the northern goshawk Accipiter gentilis. Male goshawks are responsible for providing their females and their offspring with food. We hypothesized that young males may generally show poor breeding performance or even delay breeding, because they lack the experience to hunt efficiently-especially, their principal avian prey, the feral pigeon Columba livia. Our study exploited a rare 'natural experiment', the expansion phase of an urban population, where intraspecific interference was negligible and many young males bred successfully. This enabled us to examine the improvement of foraging skills in a larger sample of young individuals, and in more controlled conditions than usually possible. Using data from individually identified male breeders, we show that, consistent with our hypothesis, the proportion of pigeons in the diet increased significantly with male age, for at least the first three years of life. Other studies have shown a parallel increase in productivity, and a positive effect of a pigeon-rich diet on brood size and nestling condition, stressing the potential fitness relevance of this prey species for goshawks. Our results suggest a causal link between patterns of age-dependence in foraging ecology and reproductive performance. Furthermore, our study is, to our knowledge, the first demonstration that prey choice of breeders, which might reflect individual hunting skills, is age-dependent in a raptor. PMID:16537129

  3. Anomalous scaling in an age-dependent branching model.

    PubMed

    Keller-Schmidt, Stephanie; Tuğrul, Murat; Eguíluz, Víctor M; Hernández-García, Emilio; Klemm, Konstantin

    2015-02-01

    We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ(-α). Depending on the exponent α, the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α=1) tree depth grows as (logn)(2). This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point. PMID:25768548

  4. Anomalous scaling in an age-dependent branching model

    NASA Astrophysics Data System (ADS)

    Keller-Schmidt, Stephanie; Tuǧrul, Murat; Eguíluz, Víctor M.; Hernández-García, Emilio; Klemm, Konstantin

    2015-02-01

    We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ-α. Depending on the exponent α , the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α =1 ) tree depth grows as (logn) 2. This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point.

  5. Particularizing Universal Education in Postcolonial Sierra Leone

    ERIC Educational Resources Information Center

    Pai, Grace

    2013-01-01

    This paper presents a vertical case study of the history of universalizing education in postcolonial Sierra Leone from the early 1950s to 1990 to highlight how there has never been a universal conception of universal education. In order to unite a nation behind a universal ideal of schooling, education needed to be adapted to different…

  6. Leon Foucault: His Life, Times and Achievements

    ERIC Educational Resources Information Center

    Aczel, Amir D.

    2004-01-01

    Leon Foucault's dramatic demonstration of the rotation of the Earth using a freely-rotating pendulum in 1850 shocked the world of science. Scientists were stunned that such a simple proof of our planet's rotation had to wait so long to be developed. Foucault's public demonstration, which was repeated at many locations around the world, put an end…

  7. Age-dependent social learning in a lizard

    PubMed Central

    Noble, Daniel W. A.; Byrne, Richard W.; Whiting, Martin J.

    2014-01-01

    Evidence of social learning, whereby the actions of an animal facilitate the acquisition of new information by another, is taxonomically biased towards mammals, especially primates, and birds. However, social learning need not be limited to group-living animals because species with less interaction can still benefit from learning about potential predators, food sources, rivals and mates. We trained male skinks (Eulamprus quoyii), a mostly solitary lizard from eastern Australia, in a two-step foraging task. Lizards belonging to ‘young’ and ‘old’ age classes were presented with a novel instrumental task (displacing a lid) and an association task (reward under blue lid). We did not find evidence for age-dependent learning of the instrumental task; however, young males in the presence of a demonstrator learnt the association task faster than young males without a demonstrator, whereas old males in both treatments had similar success rates. We present the first evidence of age-dependent social learning in a lizard and suggest that the use of social information for learning may be more widespread than previously believed. PMID:25009244

  8. Role of Mitochondrial Complex IV in Age-Dependent Obesity.

    PubMed

    Soro-Arnaiz, Ines; Li, Qilong Oscar Yang; Torres-Capelli, Mar; Meléndez-Rodríguez, Florinda; Veiga, Sónia; Veys, Koen; Sebastian, David; Elorza, Ainara; Tello, Daniel; Hernansanz-Agustín, Pablo; Cogliati, Sara; Moreno-Navarrete, Jose Maria; Balsa, Eduardo; Fuertes, Esther; Romanos, Eduardo; Martínez-Ruiz, Antonio; Enriquez, Jose Antonio; Fernandez-Real, Jose Manuel; Zorzano, Antonio; De Bock, Katrien; Aragonés, Julián

    2016-09-13

    Aging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5b silencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5B gene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion. PMID:27626667

  9. Age-dependent protection quantities for external neutron irradiation.

    PubMed

    Chou, D P; Wang, J N; Chen, I J; Chang, B J

    2003-01-01

    Based on the recommendations issued by the International Commission on Radiological Protection (ICRP), equivalent doses and effective doses for different ages are obtained for external neutron sources. The calculations at 28 neutron energies from 1 x 10(-9) MeV to 20 MeV are carried out for six irradiation geometries: AP, PA, RLAT, LLAT, ROT and ISO. An age-dependent anthropomorphic mathematical phantom series of six age groups: newborn, 1, 5, 10, 15 years old and adult is used with the Monte Carlo computer code MCNP for the dose evaluations. The results for adults are compared with those in ICRP Publication 74 and are in good agreement. At low energies the effective doses increase as the phantom age increases, but at high energics they decrease with increasing age for the AP, PA, ROT and ISO irradiation geometries. In the whole energy region the effective doses decrease as the phantom age increases for the RLAT and LLAT irradiation geometries. The age-dependent equivalent doses behave similarly to the effective doses, with some exceptions caused by the influence of the organ position. PMID:12862238

  10. Haplotyping Problem, A Clustering Approach

    SciTech Connect

    Eslahchi, Changiz; Sadeghi, Mehdi; Pezeshk, Hamid; Kargar, Mehdi; Poormohammadi, Hadi

    2007-09-06

    Construction of two haplotypes from a set of Single Nucleotide Polymorphism (SNP) fragments is called haplotype reconstruction problem. One of the most popular computational model for this problem is Minimum Error Correction (MEC). Since MEC is an NP-hard problem, here we propose a novel heuristic algorithm based on clustering analysis in data mining for haplotype reconstruction problem. Based on hamming distance and similarity between two fragments, our iterative algorithm produces two clusters of fragments; then, in each iteration, the algorithm assigns a fragment to one of the clusters. Our results suggest that the algorithm has less reconstruction error rate in comparison with other algorithms.

  11. Obituary: Leon Van Speybroeck, 1935-2002

    NASA Astrophysics Data System (ADS)

    Gorenstein, Paul; Tananbaum, Harvey Dale

    2003-12-01

    Leon Van Speybroeck, a master designer of X-ray telescope mirrors and the telescope scientist for the Chandra X-ray Observatory, died in Newton, Massachusetts, on 25 December 2002, shortly after learning that he had metastatic melanoma. Leon was born on 27 August 1935 in Wichita, Kansas. His father, Paul, was Assistant Treasurer and head of the accounting department at Beech Aircraft, and his mother, Anna Florence (Utley), was a homemaker. Both parents died in 1996. Leon's younger sister, Saundra, is a nurse and his younger brother, John, is a surgeon. Leon received a BS in 1957 and a PhD in 1965, both in physics, from MIT. His PhD thesis, ``Elastic Electron-Deuteron Scattering at High Momentum Transfer," was carried out under the supervision of Henry Kendall and Jerome Friedman. Leon spent two more years at MIT as a research associate. In 1967, he was hired by American Science and Engineering (AS&E) in Cambridge, Massachusetts, and joined the X-ray astronomy group led by Riccardo Giacconi, who received the 2002 Nobel Prize in Physics for contributions to astrophysics that led to the discovery of cosmic X-ray sources. Leon soon became involved in the design and construction of high-resolution, grazing-incidence X-ray telescopes, starting with the Apollo Telescope Mount flown on NASA's Skylab from 1973 to 1974. A series of high-resolution X-ray images of the solar corona led to dramatic changes in ideas about the solar corona, with new emphasis on magnetic dynamo processes. When the Smithsonian Astrophysical Observatory and the Harvard College Observatory morphed into the Harvard-Smithsonian Center for Astrophysics (CfA) in 1973, Leon, with Giacconi and other senior X-ray astronomers from AS&E, joined the CfA and formed the high-energy astrophysics division. Leon guided the design and development of the X-ray mirrors on NASA's Einstein Observatory, which was flown from 1978 to 1981 as the first cosmic X-ray observatory with an imaging telescope. Along the way, he

  12. Peripheral Surgical Wounding and Age-Dependent Neuroinflammation in Mice

    PubMed Central

    Wang, Hui; Culley, Deborah J.; Marcantonio, Edward R.; Crosby, Gregory; Tanzi, Rudolph E.; Zhang, Yiying; Xie, Zhongcong

    2014-01-01

    Post-operative cognitive dysfunction is associated with morbidity and mortality. However, its neuropathogenesis remains largely to be determined. Neuroinflammation and accumulation of β-amyloid (Aβ) have been reported to contribute to cognitive dysfunction in humans and cognitive impairment in animals. Our recent studies have established a pre-clinical model in mice, and have found that the peripheral surgical wounding without the influence of general anesthesia induces an age-dependent Aβ accumulation and cognitive impairment in mice. We therefore set out to assess the effects of peripheral surgical wounding, in the absence of general anesthesia, on neuroinflammation in mice with different ages. Abdominal surgery under local anesthesia was established in 9 and 18 month-old mice. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Iba1 positive cells (the marker of microglia activation), CD33, and cognitive function in mice were determined. The peripheral surgical wounding increased the levels of TNF-α, IL-6, and Iba1 positive cells in the hippocampus of both 9 and 18 month-old mice, and age potentiated these effects. The peripheral surgical wounding increased the levels of CD33 in the hippocampus of 18, but not 9, month-old mice. Finally, anti-inflammatory drug ibuprofen ameliorated the peripheral surgical wounding-induced cognitive impairment in 18 month-old mice. These data suggested that the peripheral surgical wounding could induce an age-dependent neuroinflammation and elevation of CD33 levels in the hippocampus of mice, which could lead to cognitive impairment in aged mice. Pending further studies, anti-inflammatory therapies may reduce the risk of postoperative cognitive dysfunction in elderly patients. PMID:24796537

  13. Age-dependent forest carbon sink: Estimation via inverse modeling

    NASA Astrophysics Data System (ADS)

    Zhou, Tao; Shi, Peijun; Jia, Gensuo; Dai, Yongjiu; Zhao, Xiang; Shangguan, Wei; Du, Ling; Wu, Hao; Luo, Yiqi

    2015-12-01

    Forests have been recognized to sequester a substantial amount of carbon (C) from the atmosphere. However, considerable uncertainty remains regarding the magnitude and time course of the C sink. Revealing the intrinsic relationship between forest age and C sink is crucial for reducing uncertainties in prediction of forest C sink potential. In this study, we developed a stepwise data assimilation approach to combine a process-based Terrestrial ECOsystem Regional model, observations from multiple sources, and stochastic sampling to inversely estimate carbon cycle parameters including carbon sink at different forest ages for evergreen needle-leaved forests in China. The new approach is effective to estimate age-dependent parameter of maximal light-use efficiency (R2 = 0.99) and, accordingly, can quantify a relationship between forest age and the vegetation and soil C sinks. The estimated ecosystem C sink increases rapidly with age, peaks at 0.451 kg C m-2 yr-1 at age 22 years (ranging from 0.421 to 0.465 kg C m-2 yr-1), and gradually decreases thereafter. The dynamic patterns of C sinks in vegetation and soil are significantly different. C sink in vegetation first increases rapidly with age and then decreases. C sink in soil, however, increases continuously with age; it acts as a C source when the age is less than 20 years, after which it acts as a sink. For the evergreen needle-leaved forest, the highest C sink efficiency (i.e., C sink per unit net primary productivity) is approximately 60%, with age between 11 and 43 years. Overall, the inverse estimation of carbon cycle parameters can make reasonable estimates of age-dependent C sequestration in forests.

  14. Calorie Restriction Suppresses Age-Dependent Hippocampal Transcriptional Signatures

    PubMed Central

    Schafer, Marissa J.; Dolgalev, Igor; Alldred, Melissa J.; Heguy, Adriana; Ginsberg, Stephen D.

    2015-01-01

    Calorie restriction (CR) enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan. However, the mosaic of molecular changes responsible for CR benefits remains unclear, particularly in brain regions susceptible to deterioration during aging. We examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimer’s disease (AD). Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses age-dependent signatures of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger-adult (5 months, 2.5 months of feeding) and older-adult (15 months, 12.5 months of feeding) timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa protein 1b (Hspa1b) and heat shock 70 kDa protein 5 (Hspa5), protein disulfide isomerase family A member 4 (Pdia4) and protein disulfide isomerase family A member 6 (Pdia6), and calreticulin (Calr). Expression levels of putative neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated by CR in adulthood, although the global CR-specific expression profiles at younger and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within the hippocampal CA1 sector. PMID:26221964

  15. War and deforestation in Sierra Leone

    NASA Astrophysics Data System (ADS)

    Burgess, Robin; Miguel, Edward; Stanton, Charlotte

    2015-09-01

    The impact of armed conflict on the environment is of major public policy importance. We use a geographically disaggregated dataset of civil war violence together with satellite imagery of land cover to test whether war facilitated or prevented forest loss in Sierra Leone. The conflict data set allows us to establish where rebel groups were stationed and where battles and attacks occurred. The satellite data enables to us to monitor the change in forest cover (total, primary, and secondary) in all of Sierra Leone’s 151 chiefdoms, between 1990 (prior to the war) and 2000 (just prior to its end). The results suggest that conflict in Sierra Leone acted as a brake on local deforestation: conflict-ridden areas experienced significantly less forest loss relative to their more conflict-free counterparts.

  16. Leon X-1, the First Chandra Source

    NASA Technical Reports Server (NTRS)

    Weisskopf, Martin C.; Aldcroft, Tom; Cameron, Robert A.; Gandhi, Poshak; Foellmi, Cedric; Elsner, Ronald F.; Patel, Sandeep K.; ODell, Stephen L.

    2004-01-01

    Here we present an analysis of the first photons detected with the Chandra X-ray Observatory and an identification of the brightest source in the field which we named Leon X-1 to honor the momentous contributions of the Chandra Telescope Scientist, Leon Van Speybroeck. The observation took place immediately following the opening of the last door protecting the X-ray telescope. We discuss the unusual operational conditions as the first extra-terrestrial X-ray photons reflected from the telescope onto the ACIS camera. One bright source was a p parent to the team at the control center and the small collection of photons that appeared on the monitor were sufficient to indicate that the telescope had survived the launch and was approximately in focus, even prior to any checks and subsequent adjustments.

  17. 6. SOUTHEAST ABUTMENT AT CALVERT STREET, SHOWING LEON HERMANT ALLEGORICAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. SOUTHEAST ABUTMENT AT CALVERT STREET, SHOWING LEON HERMANT ALLEGORICAL RELIEF OF TRANSPORTATION BY AUTOMOBILE - Calvert Street Bridge, Spanning Rock Creek & Potomac Parkway, Washington, District of Columbia, DC

  18. Obituary: Leon Van Speybroeck, 1935-2002

    NASA Astrophysics Data System (ADS)

    Gorenstein, Paul; Tananbaum, Harvey Dale

    2003-12-01

    Leon Van Speybroeck, a master designer of X-ray telescope mirrors and the telescope scientist for the Chandra X-ray Observatory, died in Newton, Massachusetts, on 25 December 2002, shortly after learning that he had metastatic melanoma. Leon was born on 27 August 1935 in Wichita, Kansas. His father, Paul, was Assistant Treasurer and head of the accounting department at Beech Aircraft, and his mother, Anna Florence (Utley), was a homemaker. Both parents died in 1996. Leon's younger sister, Saundra, is a nurse and his younger brother, John, is a surgeon. Leon received a BS in 1957 and a PhD in 1965, both in physics, from MIT. His PhD thesis, ``Elastic Electron-Deuteron Scattering at High Momentum Transfer," was carried out under the supervision of Henry Kendall and Jerome Friedman. Leon spent two more years at MIT as a research associate. In 1967, he was hired by American Science and Engineering (AS&E) in Cambridge, Massachusetts, and joined the X-ray astronomy group led by Riccardo Giacconi, who received the 2002 Nobel Prize in Physics for contributions to astrophysics that led to the discovery of cosmic X-ray sources. Leon soon became involved in the design and construction of high-resolution, grazing-incidence X-ray telescopes, starting with the Apollo Telescope Mount flown on NASA's Skylab from 1973 to 1974. A series of high-resolution X-ray images of the solar corona led to dramatic changes in ideas about the solar corona, with new emphasis on magnetic dynamo processes. When the Smithsonian Astrophysical Observatory and the Harvard College Observatory morphed into the Harvard-Smithsonian Center for Astrophysics (CfA) in 1973, Leon, with Giacconi and other senior X-ray astronomers from AS&E, joined the CfA and formed the high-energy astrophysics division. Leon guided the design and development of the X-ray mirrors on NASA's Einstein Observatory, which was flown from 1978 to 1981 as the first cosmic X-ray observatory with an imaging telescope. Along the way, he

  19. Implementing an Ebola Vaccine Study - Sierra Leone.

    PubMed

    Widdowson, Marc-Alain; Schrag, Stephanie J; Carter, Rosalind J; Carr, Wendy; Legardy-Williams, Jennifer; Gibson, Laura; Lisk, Durodami R; Jalloh, Mohamed I; Bash-Taqi, Donald A; Kargbo, Samuel A Sheku; Idriss, Ayesha; Deen, Gibrilla F; Russell, James B W; McDonald, Wendi; Albert, Alison P; Basket, Michelle; Callis, Amy; Carter, Victoria M; Ogunsanya, Kelli R Clifton; Gee, Julianne; Pinner, Robert; Mahon, Barbara E; Goldstein, Susan T; Seward, Jane F; Samai, Mohamed; Schuchat, Anne

    2016-01-01

    In October 2014, the College of Medicine and Allied Health Sciences of the University of Sierra Leone, the Sierra Leone Ministry of Health and Sanitation, and CDC joined the global effort to accelerate assessment and availability of candidate Ebola vaccines and began planning for the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE). STRIVE was an individually randomized controlled phase II/III trial to evaluate efficacy, immunogenicity, and safety of the recombinant vesicular stomatitis virus Ebola vaccine (rVSV-ZEBOV). The study population was health care and frontline workers in select chiefdoms of the five most affected districts in Sierra Leone. Participants were randomized to receive a single intramuscular dose of rVSV-ZEBOV at enrollment or to receive a single intramuscular dose 18-24 weeks after enrollment. All participants were followed up monthly until 6 months after vaccination. Two substudies separately assessed detailed reactogenicity over 1 month and immunogenicity over 12 months. During the 5 months before the trial, STRIVE and partners built a research platform in Sierra Leone comprising participant follow-up sites, cold chain, reliable power supply, and vaccination clinics and hired and trained at least 350 national staff. Wide-ranging community outreach, informational sessions, and messaging were conducted before and during the trial to ensure full communication to the population of the study area regarding procedures and current knowledge about the trial vaccine. During April 9-August 15, 2015, STRIVE enrolled 8,673 participants, of whom 453 and 539 were also enrolled in the safety and immunogenicity substudies, respectively. As of April 28, 2016, no Ebola cases and no vaccine-related serious adverse events, which by regulatory definition include death, life-threatening illness, hospitalization or prolongation of hospitalization, or permanent disability, were reported in the study population. Although STRIVE will not produce an

  20. Age dependence of natural uranium and thorium concentrations in bone.

    PubMed

    Larivière, Dominic; Packer, Ana Paula; Marro, Leonora; Li, Chunsheng; Chen, Jing; Cornett, R Jack

    2007-02-01

    The age dependence of the natural concentration of uranium and thorium in the skeleton was investigated using human vertebrae bone collected from two Canadian locations (Winnipeg, Manitoba, and Regina, Saskatchewan). The concentration of both radioelements in digested ashed bone samples was determined using sector-field inductively coupled plasma mass spectrometry. The geometric means for uranium level in bones showed a significant statistical difference between the two locations studied. Similarly for thorium, a statistical difference was observed, although this difference was considered marginal. The thorium concentration differed only marginally with respect to age group, indicating that its behavior in the body could be age-independent. Conversely, the uranium level in bones was found to change for the age groups tested, an indication of age-specific deposition. The age profile for uranium was comparable to the calcium turn-over rate, indicating that uranium deposition is probably, in part, dictated by this metabolic process, showing the role of present uptake into the uranium concentration in bones for populations exposed to significant uranium intake. PMID:17220713

  1. Demographic drivers of age-dependent sexual selection.

    PubMed

    Martin, A M; Festa-Bianchet, M; Coltman, D W; Pelletier, F

    2016-07-01

    Sexual selection has a critical role in evolution, and it is fundamental to identify what ecological factors drive its variation. Disentangling the ecological correlates of sexual selection over the long term, however, is challenging and has rarely been done in nature. We sought to assess how demographic changes influenced the intensity, direction and form of sexual selection and whether selective pressures varied with age. We tested whether breeder sex ratio, number of competitors and age structure influenced selection differentials on horn length of wild bighorn rams (Ovis canadensis) of different age classes on Ram Mountain, Alberta. We used 21 years of data including a detailed pedigree, demographic parameters and repeated morphological measurements. Sexual selection on horn length of males of all ages was directional and positive. Selection intensity increased with the number of competitors, reflecting male-male encounter rate during the rut, but was independent of breeder sex ratio or age structure. This result can also be linked to changes in population size because the number of competitors was highly correlated to total number of sheep. This demographic effect likely arises from age-dependent mating tactics. Males aged 2-4 years are weakly competitive and experienced stronger sexual selection as they accounted for a greater proportion of all males. Selection experienced by mature males appeared independent of demography. Our study provides a rare description of the demographic determinants of sexual selection in nature. PMID:27090379

  2. A comprehensive approach to age-dependent dosimetric modeling

    SciTech Connect

    Leggett, R.W.; Cristy, M.; Eckerman, K.F.

    1986-01-01

    In the absence of age-specific biokinetic models, current retention models of the International Commission on Radiological Protection (ICRP) frequently are used as a point of departure for evaluation of exposures to the general population. These models were designed and intended for estimation of long-term integrated doses to the adult worker. Their format and empirical basis preclude incorporation of much valuable physiological information and physiologically reasonable assumptions that could be used in characterizing the age-specific behavior of radioelements in humans. In this paper we discuss a comprehensive approach to age-dependent dosimetric modeling in which consideration is given not only to changes with age in masses and relative geometries of body organs and tissues but also to best available physiological and radiobiological information relating to the age-specific biobehavior of radionuclides. This approach is useful in obtaining more accurate estimates of long-term dose commitments as a function of age at intake, but it may be particularly valuable in establishing more accurate estimates of dose rate as a function of age. Age-specific dose rates are needed for a proper analysis of the potential effects on estimates or risk of elevated dose rates per unit intake in certain stages of life, elevated response per unit dose received during some stages of life, and age-specific non-radiogenic competing risks.

  3. Age dependency of cerebral oxygenation assessed with near infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Colier, Willy N.; van Haaren, Nicole J.; van de Ven, Marjo J.; Folgering, Hans T.; Oeseburg, Berend

    1997-04-01

    Near-IR spectroscopy (NIRS) is an optical technique that provides information on cerebral tissue oxygenation and hemodynamics on a continuous, direct, and noninvasive basis. It is used to determine cerebral blood volume (CBV) and cerebrovascular CO2 reactivity during normoxic hyper- and hypocapnia in a group of 28 healthy volunteers aged 20 to 83 years. The main focus is on to the age dependency of the measured variables. The influence of changes in minute ventilation during normocapnia on the cerebral oxygenation was also studied. The mean CBV in age was, for 20 to 30 years, 2.14 +/- 0.51 ml/100 g of brain tissue; for 45 to 50 years, 1.92 +/- 0.40 ml/100 g; and for 70 to 83 years, 1.47 +/- 0.55 ml/100 g. The CBV showed a significant decease with advancing age. No influence was found for a change in minute ventilation on cerebral oxygenation. During hypercapnia cerebral blood flow (CBF) significantly increased in al age groups, with a factor of 1.31 +/- 0.17 kPa-1, 1.64 +/- 1.39 kPa-1, and 2.4 +/- 1.7 kPa-1, respectively, for the three age groups. The difference in change among the age groups was not statistically significant. The trend seen was an increased change in CBF with advancing age. During hypocapnia, the CBF significantly decreased in all age groups, with a factor of 0.89 +/- 0.08 kPa-1, 0.89 +/- 0.04 kPa-1, and 0.85 +/- 0.11 kPa-1, respectively. There was no significant difference among the age groups.

  4. Age-Dependent Male Mating Investment in Drosophila pseudoobscura

    PubMed Central

    Dhole, Sumit; Pfennig, Karin S.

    2014-01-01

    Male mating investment can strongly influence fitness gained from a mating. Yet, male mating investment often changes with age. Life history theory predicts that mating investment should increase with age, and males should become less discriminatory about their mate as they age. Understanding age-dependent changes in male behavior and their effects on fitness is important for understanding how selection acts in age-structured populations. Although the independent effects of male or female age have been studied in many species, how these interact to influence male mating investment and fitness is less well understood. We mated Drosophila pseudoobscura males of five different age classes (4-, 8-, 11-, 15-, 19-day old) to either young (4-day) or old (11-day) females, and measured copulation duration and early post-mating fecundity. Along with their independent effects, we found a strong interaction between the effects of male and female ages on male mating investment and fitness from individual matings. Male mating investment increased with male age, but this increase was more prominent in matings with young females. Male D. pseudoobscura made smaller investments when mating with old females. The level of such discrimination based on female age, however, also changed with male age. Intermediate aged males were most discriminatory, while the youngest and the oldest males did not discriminate between females of different ages. We also found that larger male mating investments resulted in higher fitness payoffs. Our results show that male and female ages interact to form a complex pattern of age-specific male mating investment and fitness. PMID:24586373

  5. Indigenous Knowledge and Library Work in Sierra Leone

    ERIC Educational Resources Information Center

    Kargbo, John Abdul

    2006-01-01

    Indigenous knowledge is vital information that is sadly diminishing at an alarming rate in Sierra Leone. There is, therefore, an urgent need to collect it before much of it is completely lost. This article explores the concept of indigenous knowledge and indigenous knowledge systems with a particular focus on Sierra Leone. Definitions and…

  6. Age Dependent Absolute Plate and Plume Motion Modeling

    NASA Astrophysics Data System (ADS)

    Heaton, D. E.; Koppers, A. A. P.

    2015-12-01

    construct rapidly and represent a time period close to the inception age of the seamount, thus by proxy also the hotspot location. Here we present a new age dependent plate motion model that tests the 'fixed' and 'moving' hotspot hypotheses.

  7. Age-dependent morphological and compositional variations on Ceres

    NASA Astrophysics Data System (ADS)

    Jaumann, Ralf

    2016-04-01

    Extended smooth plains cover the interior of a number of craters on Ceres. Smooth plains appear on different topographic levels associated with pits and flow-like features that overrun crater rims. The material forming these plains also ponds in depressions and smaller craters and cover the pre-existing surface creating distinct geological boundaries. Ikapati crater shows smooth plains on different topographic levels associated with pits and flow-like features that overrun crater rims. The material forming these plains, ponds in depressions and smaller craters and cover the pre-existing surface creating a distinct geological boundary. The interior of Occator also exhibits extended plains of ponded material, multiple flows originating from the center overwhelming the mass wasting deposits from the rim, dome-like features, vents cracks and fissures. Furthermore, crater densities on Occator's floor are lower than those on the ejecta blanket indicating a post-impact formation age of the flows. The flows to the northeast appear to originate from the central region and move slightly uphill. This indicates either a feeding zone that pushes the flows forward by supplying low-viscosity material or a depression of the crater center, possibly after discharging a subsurface reservoir. The plains and flows as well as some areas surrounding the craters appear spectrally blue. Both plains and flow material are characterized in camera and spectrometer visible spectra by a slightly negative slope with a gradual drop off up to 10% in reflectance from 0.5μm to 1μm. Although the spectral variations in the visible are subtle, they are clearly expressed in the color ratio composite. The crater densities of 20 locations across the surface of Ceres with different spectral behavior were analyzed in order to investigate the age dependence of spectral surface features. The results indicate that bluish material is mainly associated with the youngest impact craters on Ceres (< 0.5 Ga) while

  8. Treatment of neuropathic pain in Sierra Leone.

    PubMed

    Lacoux, Phillipe; Ford, Nathan

    2002-07-01

    During Sierra Leone's violent decade-long war, the warring parties used amputation, especially of arms, as a means of terror. In a camp for amputees in the capital city Freetown, Médecins Sans Frontières established a clinic and a treatment programme for neuropathic pain. Insecurity and cultural and language barriers have complicated this work, but medical and humanitarian benefits have been demonstrated. Pain services are virtually non-existent in less-developed countries. There have recently been no major treatment advances for neuropathic or phantom pain; however, the general body of knowledge about amputation pain can be increased by observations from these difficult settings. PMID:12849488

  9. Undiagnosed Acute Viral Febrile Illnesses, Sierra Leone

    PubMed Central

    Rossi, Cynthia A.; Khan, Sheik H.; Goba, Augustine; Fair, Joseph N.

    2014-01-01

    Sierra Leone in West Africa is in a Lassa fever–hyperendemic region that also includes Guinea and Liberia. Each year, suspected Lassa fever cases result in submission of ≈500–700 samples to the Kenema Government Hospital Lassa Diagnostic Laboratory in eastern Sierra Leone. Generally only 30%–40% of samples tested are positive for Lassa virus (LASV) antigen and/or LASV-specific IgM; thus, 60%–70% of these patients have acute diseases of unknown origin. To investigate what other arthropod-borne and hemorrhagic fever viral diseases might cause serious illness in this region and mimic Lassa fever, we tested patient serum samples that were negative for malaria parasites and LASV. Using IgM-capture ELISAs, we evaluated samples for antibodies to arthropod-borne and other hemorrhagic fever viruses. Approximately 25% of LASV-negative patients had IgM to dengue, West Nile, yellow fever, Rift Valley fever, chikungunya, Ebola, and Marburg viruses but not to Crimean-Congo hemorrhagic fever virus. PMID:24959946

  10. Detecting structure of haplotypes and local ancestry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We present a two-layer hidden Markov model to detect the structure of haplotypes for unrelated individuals. This allows us to model two scales of linkage disequilibrium (one within a group of haplotypes and one between groups), thereby taking advantage of rich haplotype information to infer local an...

  11. HaplotypeCN: copy number haplotype inference with Hidden Markov Model and localized haplotype clustering.

    PubMed

    Lin, Yen-Jen; Chen, Yu-Tin; Hsu, Shu-Ni; Peng, Chien-Hua; Tang, Chuan-Yi; Yen, Tzu-Chen; Hsieh, Wen-Ping

    2014-01-01

    Copy number variation (CNV) has been reported to be associated with disease and various cancers. Hence, identifying the accurate position and the type of CNV is currently a critical issue. There are many tools targeting on detecting CNV regions, constructing haplotype phases on CNV regions, or estimating the numerical copy numbers. However, none of them can do all of the three tasks at the same time. This paper presents a method based on Hidden Markov Model to detect parent specific copy number change on both chromosomes with signals from SNP arrays. A haplotype tree is constructed with dynamic branch merging to model the transition of the copy number status of the two alleles assessed at each SNP locus. The emission models are constructed for the genotypes formed with the two haplotypes. The proposed method can provide the segmentation points of the CNV regions as well as the haplotype phasing for the allelic status on each chromosome. The estimated copy numbers are provided as fractional numbers, which can accommodate the somatic mutation in cancer specimens that usually consist of heterogeneous cell populations. The algorithm is evaluated on simulated data and the previously published regions of CNV of the 270 HapMap individuals. The results were compared with five popular methods: PennCNV, genoCN, COKGEN, QuantiSNP and cnvHap. The application on oral cancer samples demonstrates how the proposed method can facilitate clinical association studies. The proposed algorithm exhibits comparable sensitivity of the CNV regions to the best algorithm in our genome-wide study and demonstrates the highest detection rate in SNP dense regions. In addition, we provide better haplotype phasing accuracy than similar approaches. The clinical association carried out with our fractional estimate of copy numbers in the cancer samples provides better detection power than that with integer copy number states. PMID:24849202

  12. TUMOR HAPLOTYPE ASSEMBLY ALGORITHMS FOR CANCER GENOMICS

    PubMed Central

    AGUIAR, DEREK; WONG, WENDY S.W.; ISTRAIL, SORIN

    2014-01-01

    The growing availability of inexpensive high-throughput sequence data is enabling researchers to sequence tumor populations within a single individual at high coverage. But, cancer genome sequence evolution and mutational phenomena like driver mutations and gene fusions are difficult to investigate without first reconstructing tumor haplotype sequences. Haplotype assembly of single individual tumor populations is an exceedingly difficult task complicated by tumor haplotype heterogeneity, tumor or normal cell sequence contamination, polyploidy, and complex patterns of variation. While computational and experimental haplotype phasing of diploid genomes has seen much progress in recent years, haplotype assembly in cancer genomes remains uncharted territory. In this work, we describe HapCompass-Tumor a computational modeling and algorithmic framework for haplotype assembly of copy number variable cancer genomes containing haplotypes at different frequencies and complex variation. We extend our polyploid haplotype assembly model and present novel algorithms for (1) complex variations, including copy number changes, as varying numbers of disjoint paths in an associated graph, (2) variable haplotype frequencies and contamination, and (3) computation of tumor haplotypes using simple cycles of the compass graph which constrain the space of haplotype assembly solutions. The model and algorithm are implemented in the software package HapCompass-Tumor which is available for download from http://www.brown.edu/Research/Istrail_Lab/. PMID:24297529

  13. Projected Treatment Capacity Needs in Sierra Leone

    PubMed Central

    White, Richard A; MacDonald, Emily; de Blasio, Birgitte Freiesleben; Nygård, Karin; Vold, Line; Røttingen, John-Arne

    2015-01-01

    Background: The ongoing outbreak of Ebola Virus Disease in West Africa requires immediate and sustained input from the international community in order to curb transmission. The CDC has produced a model that indicates that to end the outbreak by pushing the reproductive number below one, 25% of the patients must be placed in an Ebola Treatment Unit (ETC) and 45% must be isolated in community settings in which risk of disease transmission is reduced and safe burials are provided. In order to provide firmer targets for the international response in Sierra Leone, we estimated the national and international personnel and treatment capacity that may be required to reach these percentages. Methods: We developed a compartmental SEIR model that was fitted to WHO data and local data allowing the reproductive number to change every 8 weeks to forecast the progression of the EVD epidemic in Sierra Leone. We used the previously estimated 2.5x correction factor estimated by the CDC to correct for underreporting. Number of personnel required to provide treatment for the predicted number of cases was estimated using UNMEER and UN OCHA requests for resources required to meet the CDC target of 70% isolation. Results: As of today (2014-12-04), we estimate that there are 810 (95% CI=646 to 973) EVD active cases in treatment, with an additional 3751 (95% CI=2778 to 4723) EVD cases unreported and untreated. To reach the CDC targets today, we need 1140 (95% CI=894 to 1387) cases in ETCs and 2052 (95% CI=1608 to 2496) at home or in a community setting with a reduced risk for disease transmission. In 28 days (2015-01-01), we will need 1309 (95% CI=804 to 1814) EVD cases in ETCs and 2356 (95% CI=1447 to 3266) EVD cases at reduced risk of transmission. If the current transmission rate is not reduced, up to 3183 personnel in total will be required in 56 days (2015-01-29) to operate ETCs according to our model. Conclusions: The current outbreak will require massive input from the

  14. Initiatives for Sustainable Community Development in Sierra Leone.

    ERIC Educational Resources Information Center

    Kamara, John M.; Kargbo, Stephen B.

    1999-01-01

    In Sierra Leone, two church-sponsored programs are focused on sustainable development. The Wesleyan Development Education and Awareness Programme trains people to initiate community projects. Women's Loan Scheme encourages development of small-scale enterprises. (SK)

  15. Haplotype studies in Wilson disease

    SciTech Connect

    Thomas, G.R.; Bull, P.C.; Roberts, E.A.; Cox, D.W.; Walshe, J.M. )

    1994-01-01

    In 51 families with Wilson disease, the authors have studied DNA haplotypes of dinucleotide repeat polymorphisms (CA repeats) in the 13q14.3 region, to examine these markers for association with the Wilson disease gene (WND). In addition to a marker (D13S133) described elsewhere, the authors have developed three new highly polymorphic markers (D13S314, D13S315, and D13S316) close to the WND locus. The authors have examined the distribution of marker alleles at the loci studied and have found that D13S314, D13S133, and D13S316 each show nonrandom distribution on chromosomes carrying the WND mutation. The authors have studied haplotypes of these three markers and have found that there are highly significant differences between WND and normal haplotypes in northern European families. These findings have important implications for mutation detection and molecular diagnosis in families with Wilson disease. 25 refs., 2 figs., 5 tabs.

  16. Fatal parathion poisoning in Sierra Leone

    PubMed Central

    Etzel, R. A.; Forthal, D. N.; Hill, R. H.; Demby, A.

    1987-01-01

    In May and June 1986, 49 persons in Sierra Leone were acutely poisoned by the organothiophosphate insecticide, parathion. Fourteen people died. Illness occurred in three episodes at two different locations that were 44 km apart. A study of 21 cases and 22 household controls was undertaken to explore which factors were associated with the development of the symptoms. Cases were more likely than controls to have eaten bread in the 4 hours before becoming ill (odds ratio, 12.7; 95% confidence interval, 2.4-83.8). Scrapings of residue from the floor of the truck that had brought the wheat flour from the mill to the general store where the baker purchased it were positive for parathion, suggesting that the flour had been contaminated during transport. Pesticide poisoning is a common problem in the developing world, and public health measures such as restricting the use of parathion may help to prevent fatal poisonings. PMID:3501344

  17. Towards an Analytical Age-Dependent Model of Contrast Sensitivity Functions for an Ageing Society

    PubMed Central

    Joulan, Karine; Brémond, Roland

    2015-01-01

    The Contrast Sensitivity Function (CSF) describes how the visibility of a grating depends on the stimulus spatial frequency. Many published CSF data have demonstrated that contrast sensitivity declines with age. However, an age-dependent analytical model of the CSF is not available to date. In this paper, we propose such an analytical CSF model based on visual mechanisms, taking into account the age factor. To this end, we have extended an existing model from Barten (1999), taking into account the dependencies of this model's optical and physiological parameters on age. Age-dependent models of the cones and ganglion cells densities, the optical and neural MTF, and optical and neural noise are proposed, based on published data. The proposed age-dependent CSF is finally tested against available experimental data, with fair results. Such an age-dependent model may be beneficial when designing real-time age-dependent image coding and display applications. PMID:26078994

  18. Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan.

    PubMed

    Chen, Shuang; Brunskill, Eric W; Potter, S Steven; Dexheimer, Phillip J; Salomonis, Nathan; Aronow, Bruce J; Hong, Christian I; Zhang, Tongli; Kopan, Raphael

    2015-10-12

    During fetal development, nephrons of the metanephric kidney form from a mesenchymal progenitor population that differentiates en masse before or shortly after birth. We explored intrinsic and extrinsic mechanisms controlling progenitor lifespan in a transplantation assay that allowed us to compare engraftment of old and young progenitors into the same young niche. The progenitors displayed an age-dependent decrease in proliferation and concomitant increase in niche exit rates. Single-cell transcriptome profiling revealed progressive age-dependent changes, with heterogeneity increasing in older populations. Age-dependent elevation in mTor and reduction in Fgf20 could contribute to increased exit rates. Importantly, 30% of old progenitors remained in the niche for up to 1 week post engraftment, a net gain of 50% to their lifespan, but only if surrounded by young neighbors. We provide evidence in support of a model in which intrinsic age-dependent changes affect inter-progenitor interactions that drive cessation of nephrogenesis. PMID:26460946

  19. Post-Ebola Syndrome, Sierra Leone

    PubMed Central

    Sesay, Foday R.; Massaquoi, Thomas A.; Idriss, Baimba R.; Sahr, Foday; Semple, Malcolm G.

    2016-01-01

    Thousands of persons have survived Ebola virus disease. Almost all survivors describe symptoms that persist or develop after hospital discharge. A cross-sectional survey of the symptoms of all survivors from the Ebola treatment unit (ETU) at 34th Regimental Military Hospital, Freetown, Sierra Leone (MH34), was conducted after discharge at their initial follow-up appointment within 3 weeks after their second negative PCR result. From its opening on December 1, 2014, through March 31, 2015, the MH34 ETU treated 84 persons (8–70 years of age) with PCR-confirmed Ebola virus disease, of whom 44 survived. Survivors reported musculoskeletal pain (70%), headache (48%), and ocular problems (14%). Those who reported headache had had lower admission cycle threshold Ebola PCR than did those who did not (p<0.03). This complete survivor cohort from 1 ETU enables analysis of the proportion of symptoms of post-Ebola syndrome. The Ebola epidemic is waning, but the effects of the disease will remain. PMID:26983037

  20. Post-Ebola Syndrome, Sierra Leone.

    PubMed

    Scott, Janet T; Sesay, Foday R; Massaquoi, Thomas A; Idriss, Baimba R; Sahr, Foday; Semple, Malcolm G

    2016-04-01

    Thousands of persons have survived Ebola virus disease. Almost all survivors describe symptoms that persist or develop after hospital discharge. A cross-sectional survey of the symptoms of all survivors from the Ebola treatment unit (ETU) at 34th Regimental Military Hospital, Freetown, Sierra Leone (MH34), was conducted after discharge at their initial follow-up appointment within 3 weeks after their second negative PCR result. From its opening on December 1, 2014, through March 31, 2015, the MH34 ETU treated 84 persons (8-70 years of age) with PCR-confirmed Ebola virus disease, of whom 44 survived. Survivors reported musculoskeletal pain (70%), headache (48%), and ocular problems (14%). Those who reported headache had had lower admission cycle threshold Ebola PCR than did those who did not (p<0.03). This complete survivor cohort from 1 ETU enables analysis of the proportion of symptoms of post-Ebola syndrome. The Ebola epidemic is waning, but the effects of the disease will remain. PMID:26983037

  1. Filling in missing genotypes using haplotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Unknown genotypes can be made known (imputed) from observed genotypes at the same or nearby loci of relatives using pedigree haplotyping, or from matching allele patterns (regardless of pedigree) using population haplotyping. Fortran program findhap.f90 was designed to combine population and pedigre...

  2. Ebola Surveillance - Guinea, Liberia, and Sierra Leone.

    PubMed

    McNamara, Lucy A; Schafer, Ilana J; Nolen, Leisha D; Gorina, Yelena; Redd, John T; Lo, Terrence; Ervin, Elizabeth; Henao, Olga; Dahl, Benjamin A; Morgan, Oliver; Hersey, Sara; Knust, Barbara

    2016-01-01

    Developing a surveillance system during a public health emergency is always challenging but is especially so in countries with limited public health infrastructure. Surveillance for Ebola virus disease (Ebola) in the West African countries heavily affected by Ebola (Guinea, Liberia, and Sierra Leone) faced numerous impediments, including insufficient numbers of trained staff, community reticence to report cases and contacts, limited information technology resources, limited telephone and Internet service, and overwhelming numbers of infected persons. Through the work of CDC and numerous partners, including the countries' ministries of health, the World Health Organization, and other government and nongovernment organizations, functional Ebola surveillance was established and maintained in these countries. CDC staff were heavily involved in implementing case-based surveillance systems, sustaining case surveillance and contact tracing, and interpreting surveillance data. In addition to helping the ministries of health and other partners understand and manage the epidemic, CDC's activities strengthened epidemiologic and data management capacity to improve routine surveillance in the countries affected, even after the Ebola epidemic ended, and enhanced local capacity to respond quickly to future public health emergencies. However, the many obstacles overcome during development of these Ebola surveillance systems highlight the need to have strong public health, surveillance, and information technology infrastructure in place before a public health emergency occurs. Intense, long-term focus on strengthening public health surveillance systems in developing countries, as described in the Global Health Security Agenda, is needed.The activities summarized in this report would not have been possible without collaboration with many U.S and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). PMID:27389614

  3. Haplotypes and mutations in Wilson disease

    SciTech Connect

    Thomas, G.R.; Roberts, E.A.; Cox, D.W.

    1995-06-01

    Wilson disease is a disorder of copper transport, resulting in neurological and hepatic damage due to copper toxicity. We have recently identified >20 mutations in the copper-transporting ATPase defective in this disease. Given the difficulties of searching for mutations in a gene spanning >80 kb of genomic DNA, haplotype data are important as a guide to mutation detection. Here we examine the haplotypes associated with specific mutations. We have extended previous studies of DNA haplotypes of dinucleotide-repeat polymorphisms (CA repeats) in the Wilson disease region to include an additional marker, in 58 families. These haplotypes, combining three markers (D13S314, D12S316, and D13S301), are usually specific for each different mutation, even though highly polymorphic CA repeat markers have been used. Haplotypes, as well as their accompanying mutations, differ between populations. In the patients whom we have studied, the haplotype data indicate that as many as 20 mutations may still be unidentified. The use of the haplotypes that we have identified provides an important guide for the identification of known mutations and can facilitate future mutation searches. 15 refs., 1 fig., 2 tabs.

  4. Modelling Anopheles gambiae s.s. Population Dynamics with Temperature- and Age-Dependent Survival.

    PubMed

    Christiansen-Jucht, Céline; Erguler, Kamil; Shek, Chee Yan; Basáñez, María-Gloria; Parham, Paul E

    2015-06-01

    Climate change and global warming are emerging as important threats to human health, particularly through the potential increase in vector- and water-borne diseases. Environmental variables are known to affect substantially the population dynamics and abundance of the poikilothermic vectors of disease, but the exact extent of this sensitivity is not well established. Focusing on malaria and its main vector in Africa, Anopheles gambiae sensu stricto, we present a set of novel mathematical models of climate-driven mosquito population dynamics motivated by experimental data suggesting that in An. gambiae, mortality is temperature and age dependent. We compared the performance of these models to that of a "standard" model ignoring age dependence. We used a longitudinal dataset of vector abundance over 36 months in sub-Saharan Africa for comparison between models that incorporate age dependence and one that does not, and observe that age-dependent models consistently fitted the data better than the reference model. This highlights that including age dependence in the vector component of mosquito-borne disease models may be important to predict more reliably disease transmission dynamics. Further data and studies are needed to enable improved fitting, leading to more accurate and informative model predictions for the An. gambiae malaria vector as well as for other disease vectors. PMID:26030468

  5. Modelling Anopheles gambiae s.s. Population Dynamics with Temperature- and Age-Dependent Survival

    PubMed Central

    Christiansen-Jucht, Céline; Erguler, Kamil; Shek, Chee Yan; Basáñez, María-Gloria; Parham, Paul E.

    2015-01-01

    Climate change and global warming are emerging as important threats to human health, particularly through the potential increase in vector- and water-borne diseases. Environmental variables are known to affect substantially the population dynamics and abundance of the poikilothermic vectors of disease, but the exact extent of this sensitivity is not well established. Focusing on malaria and its main vector in Africa, Anopheles gambiae sensu stricto, we present a set of novel mathematical models of climate-driven mosquito population dynamics motivated by experimental data suggesting that in An. gambiae, mortality is temperature and age dependent. We compared the performance of these models to that of a “standard” model ignoring age dependence. We used a longitudinal dataset of vector abundance over 36 months in sub-Saharan Africa for comparison between models that incorporate age dependence and one that does not, and observe that age-dependent models consistently fitted the data better than the reference model. This highlights that including age dependence in the vector component of mosquito-borne disease models may be important to predict more reliably disease transmission dynamics. Further data and studies are needed to enable improved fitting, leading to more accurate and informative model predictions for the An. gambiae malaria vector as well as for other disease vectors. PMID:26030468

  6. Sickle cell disorder, beta-globin gene cluster haplotypes and alpha-thalassemia in neonates and adults from Guadeloupe.

    PubMed

    Kéclard, L; Romana, M; Lavocat, E; Saint-Martin, C; Berchel, C; Mérault, G

    1997-05-01

    We have studied haplotype of beta(S) chromosome and alpha-globin gene status in 534 patients (255 adults and 279 children of whom 159 neonates) from Guadeloupe with various sickle cell-related conditions, namely SS (n = 298), SC (n = 170), S-beta-thal (n = 56), and other rare forms (n = 10). Haplotype data on beta(S) chromosomes confirm our previous observation that Benin type is the most prevalent (75%) beta(S) chromosome in Guadeloupe, in disagreement with the historical records. Comparison of the frequency of distribution of various beta(S) haplotypes between neonates and adults on the one hand and between SS and SC cases on the other shows that the current beta(S) haplotype distribution in this island is not distorted by haplotype-related differential survival. We also show that the frequency of alpha-thalassemia (-3.7 kb) in Guadeloupe is one of the highest recorded in this region involved in Atlantic slave trade and also failed to reveal any age-dependent increase in frequency. We conclude that the African component of Guadeloupe is distinct from that of Brazil and Cuba but is close to that of Jamaica. PMID:9136913

  7. Alternative haplotype construction methods for genomic evaluation.

    PubMed

    Jónás, Dávid; Ducrocq, Vincent; Fouilloux, Marie-Noëlle; Croiseau, Pascal

    2016-06-01

    Genomic evaluation methods today use single nucleotide polymorphism (SNP) as genomic markers to trace quantitative trait loci (QTL). Today most genomic prediction procedures use biallelic SNP markers. However, SNP can be combined into short, multiallelic haplotypes that can improve genomic prediction due to higher linkage disequilibrium between the haplotypes and the linked QTL. The aim of this study was to develop a method to identify the haplotypes, which can be expected to be superior in genomic evaluation, as compared with either SNP or other haplotypes of the same size. We first identified the SNP (termed as QTL-SNP) from the bovine 50K SNP chip that had the largest effect on the analyzed trait. It was assumed that these SNP were not the causative mutations and they merely indicated the approximate location of the QTL. Haplotypes of 3, 4, or 5 SNP were selected from short genomic windows surrounding these markers to capture the effect of the QTL. Two methods described in this paper aim at selecting the most optimal haplotype for genomic evaluation. They assumed that if an allele has a high frequency, its allele effect can be accurately predicted. These methods were tested in a classical validation study using a dairy cattle population of 2,235 bulls with genotypes from the bovine 50K SNP chip and daughter yield deviations (DYD) on 5 dairy cattle production traits. Combining the SNP into haplotypes was beneficial with all tested haplotypes, leading to an average increase of 2% in terms of correlations between DYD and genomic breeding value estimates compared with the analysis when the same SNP were used individually. Compared with haplotypes built by merging the QTL-SNP with its flanking SNP, the haplotypes selected with the proposed criteria carried less under- and over-represented alleles: the proportion of alleles with frequencies <1 or >40% decreased, on average, by 17.4 and 43.4%, respectively. The correlations between DYD and genomic breeding value

  8. Age-dependence of lipid parameters in the general population and vegetarians.

    PubMed

    Richter, V; Rassoul, F; Hentschel, B; Kothe, K; Krobara, M; Unger, R; Purschwitz, K; Rotzsch, W; Thiery, J; Muradian, K

    2004-06-01

    Age-dependent changes of lipid metabolism may arise both as a result of mechanisms of biological ageing and factors influencing age-dependent changes. To study possible influences of nutrition and life-style of vegetarians on age-dependence of lipid parameters, subjects of general population were compared with vegetarians. In the frame of population-based lipid screening projects in the city of Leipzig/Germany (Lipid Study Leipzig, LSL) 10 550 subjects (3,816 men and 6,734 women, age 18-99 years) of general population were compared with 417 vegetarians (vegans, lacto-vegetarians, lacto-ovo-vegetarians, 148 men and 269 women, age 18-93 years). Most of the vegetarians included in the study were members of the German Society of Vegetarians. The study program included capillary blood cholesterol measurements and the determination of high-density lipoprotein (HDL)-cholesterol, the measurement of other cardiovascular risk factors and the evaluation of dietary and life-style factors. Evaluation of cardiovascular risk profile within LSL was connected with individual consultation. The mean total cholesterol and non-HDL-cholesterol level and the total: HDL-cholesterol ratio showed the expected age-dependence, with maximum values within the decade 60-70 years. Vegetarians showed lower total and non-HDL-cholesterol levels in comparison with the general population. Furthermore, the age-dependent increase of these parameters is less pronounced under the conditions of vegetarian nutrition and life-style. Especially in young adulthood a significant difference is observed. Thus, the results of the present study reveal the role of nutritional and life-style factors that determine the lipid profile on a population basis and suggest that the known age-dependent rise of the level of atherogenic plasma lipoproteins is partly preventable. PMID:15224241

  9. Phylogenetic Analysis of West Nile Virus, Nuevo Leon State, Mexico

    PubMed Central

    Blitvich, Bradley J.; Fernández-Salas, Ildefonso; Contreras-Cordero, Juan F.; Loroño-Pino, María A.; Marlenee, Nicole L.; Díaz, Francisco J.; González-Rojas, José I.; Obregón-Martínez, Nelson; Chiu-García, Jorge A.; Black, William C.

    2004-01-01

    West Nile virus RNA was detected in brain tissue from a horse that died in June 2003 in Nuevo Leon State, Mexico. Nucleotide sequencing and phylogenetic analysis of the premembrane and envelope genes showed that the virus was most closely related to West Nile virus isolates collected in Texas in 2002. PMID:15324558

  10. Life in Sierra Leone, West Africa. A Teaching Unit.

    ERIC Educational Resources Information Center

    Corby, Richard A.

    This unit is designed for students in grades 6-12. The unit provides an introduction to Sierra Leone and the continent of Africa through basic concepts and a conceptual framework for learning. The unit is divided into 17 activities. Activities include: (1) "Stereotypes and Myths about African and Africans"; (2) "The Manding Name Game"; (3) "Common…

  11. Leon Cooper's Perspective on Teaching Science: An Interview Study

    ERIC Educational Resources Information Center

    Niaz, Mansoor; Klassen, Stephen; McMillan, Barbara; Metz, Don

    2010-01-01

    The authors of this paper portray the perspective of Professor Leon Cooper, a theoretical physicist, Nobel laureate, active researcher, and physics textbook author, on teaching science and on the nature of science (NOS). The views presented emerged from an interview prepared by the authors and responded to in writing by Professor Cooper. Based on…

  12. School Libraries in Sierra Leone's Educational System: Quo Vadis?

    ERIC Educational Resources Information Center

    Kargbo, John A.

    2003-01-01

    Examines the role of school libraries in Sierra Leone's (Africa) educational system and the problems affecting their development. Discusses the need for materials to support teaching activities; sociological factors; teachers' and students' information needs; current trends and changes; rural areas with no school libraries; and lack of standards,…

  13. School-Based Peace Building in Sierra Leone

    ERIC Educational Resources Information Center

    Bretherton, Diane; Weston, Jane; Zbar, Vic

    2005-01-01

    This article describes the development of a peace education project, including the Peace Education Kit, in schools in Sierra Leone. The program, initiated by the World Bank, has involved working partnerships between local and international agencies and provides a case study of how schools can work with the community to contribute to a national…

  14. A New Agenda for Adult Education in Sierra Leone.

    ERIC Educational Resources Information Center

    Skelt, Joanna

    2003-01-01

    After years of conflict, Sierra Leone has critical educational development needs including trauma healing and conflict resolution, rebuilding of the educational infrastructure, and citizenship and capacity building. Citizenship education in this context must be redefined as developing individual agency and encouraging active participation. (SK)

  15. Library Education and the Practitioner: The Sierra Leone Experience.

    ERIC Educational Resources Information Center

    Kargbo, John Abdul

    1999-01-01

    Examines the past and current educational trends of librarianship in Sierra Leone. Discuses courses offered in the current library school; economic and political issues affecting higher education; the need for full-time faculty; general versus specialized practitioner needs; attitudes of faculty toward working librarians; and professional…

  16. Why High School Must Go: An Interview with Leon Botstein

    ERIC Educational Resources Information Center

    Epstein, Robert

    2007-01-01

    This article presents an interview with Leon Botstein, longtime president of Bard College, as well as music director and conductor of the American and Jerusalem symphony orchestras. Botstein talks about his book entitled "Jefferson's Children: Education and the Promise of American Culture" and his views about teens and high schools in America.…

  17. Measuring the impact of Ebola control measures in Sierra Leone

    PubMed Central

    Kucharski, Adam J.; Camacho, Anton; Flasche, Stefan; Glover, Rebecca E.; Edmunds, W. John; Funk, Sebastian

    2015-01-01

    Between September 2014 and February 2015, the number of Ebola virus disease (EVD) cases reported in Sierra Leone declined in many districts. During this period, a major international response was put in place, with thousands of treatment beds introduced alongside other infection control measures. However, assessing the impact of the response is challenging, as several factors could have influenced the decline in infections, including behavior changes and other community interventions. We developed a mathematical model of EVD transmission, and measured how transmission changed over time in the 12 districts of Sierra Leone with sustained transmission between June 2014 and February 2015. We used the model to estimate how many cases were averted as a result of the introduction of additional treatment beds in each area. Examining epidemic dynamics at the district level, we estimated that 56,600 (95% credible interval: 48,300–84,500) Ebola cases (both reported and unreported) were averted in Sierra Leone up to February 2, 2015 as a direct result of additional treatment beds being introduced. We also found that if beds had been introduced 1 month earlier, a further 12,500 cases could have been averted. Our results suggest the unprecedented local and international response led to a substantial decline in EVD transmission during 2014–2015. In particular, the introduction of beds had a direct impact on reducing EVD cases in Sierra Leone, although the effect varied considerably between districts. PMID:26460023

  18. Power in Practice: Trade Union Education in Sierra Leone

    ERIC Educational Resources Information Center

    Stirling, John

    2013-01-01

    This article presents an analysis of the development of a trade union education program in Sierra Leone in the geo-historical context of British colonialism. It places the argument in relation to the contradictory trends of trade unionism more generally and alongside their antagonistic cooperation with capitalism. It discusses the limits and…

  19. Home Alone: Children as Caretakers in Leon, Nicaragua

    ERIC Educational Resources Information Center

    Dahlblom, Kjerstin; Herrara, Andres Rodriguez; Pena, Rodolfo; Dahlgren, Lars

    2009-01-01

    This article seeks to explore and understand the life situations of sibling caretakers in poor areas in Leon, Nicaragua. The every day lives for caretakers were studied through observations and interviews with children, informants and parents. The children themselves were satisfied and proud to be trusted as caretakers and felt useful in…

  20. Reemergence of chikungunya virus in Bo, Sierra Leone.

    PubMed

    Ansumana, Rashid; Jacobsen, Kathryn H; Leski, Tomasz A; Covington, Andrea L; Bangura, Umaru; Hodges, Mary H; Lin, Baochuan; Bockarie, Alfred S; Lamin, Joseph M; Bockarie, Moses J; Stenger, David A

    2013-07-01

    We diagnosed 400 possible IgM-positive cases of chikungunya virus in Bo, Sierra Leone, during July 2012-January 2013 by using lateral flow immunoassays. Cases detected likely represent only a small fraction of total cases. Further laboratory testing is required to confirm this outbreak and characterize the virus. PMID:23764023

  1. Reemergence of Chikungunya Virus in Bo, Sierra Leone

    PubMed Central

    Ansumana, Rashid; Leski, Tomasz A.; Covington, Andrea L.; Bangura, Umaru; Hodges, Mary H.; Lin, Baochuan; Bockarie, Alfred S.; Lamin, Joseph M.; Bockarie, Moses J.; Stenger, David A.

    2013-01-01

    We diagnosed 400 possible IgM-positive cases of chikungunya virus in Bo, Sierra Leone, during July 2012–January 2013 by using lateral flow immunoassays. Cases detected likely represent only a small fraction of total cases. Further laboratory testing is required to confirm this outbreak and characterize the virus. PMID:23764023

  2. Land Lab Experiences in Sierra Leone and Illinois

    ERIC Educational Resources Information Center

    Swanson, Burton E.; Tucker, Sonny W.

    1978-01-01

    The agricultural education curriculum at Njala University College, University of Sierra Leone, is stressing practical farm experience programs on school land for students preparing to teach agriculture. In Illinois also the "land laboratories" concept appears to be effective in providing practical agricultural training. (MF)

  3. The Science Curriculum and the Secondary Student in Sierra Leone.

    ERIC Educational Resources Information Center

    Sawyerr, Ebun S.

    1985-01-01

    Describes the new primary and secondary-level science curriculum in Sierra Leone as well as new teacher roles and instructional approaches. Indicates that curricular changes in this country should address needs related to job opportunities, the environment, and citizenship. Results of 1972-80 secondary-level biology, chemistry, and physics…

  4. Finding Uncertainties that Cause the Age Dependence of Dose Limits to Be Immature

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.

    2007-01-01

    Space radiation permissible exposure limits (PEL) are intended to set acceptable levels of cancer risks, and avoid any clinical significant non-cancer effects. The 1989 recommendation of the National Council of Radiation Protection and Measurements (NCRP) recommended a strong age dependence of dose limits that departed drastically from the then mature 1970 dose limits recommendations from the National Academy of Science, which were independent of age. In 2000, the NCRP recommended revised limits that showed a similar trend of risk with age to the 1989 report. In this model, the cancer risk per Sv varies by more than 2-fold for ages between 30- and 50-yr. Therefore for galactic cosmic rays exposure, astronaut age has a larger influence on risk then radiation shielding mass or material composition, vehicle propulsion method, or position in the solar cycle. For considering the control of mission costs and resources, the possibility of using astronaut age as a trade variable in mission design could be considered. However, the uncertainties in describing the age dependence on risk have not been fully explored. We discuss biological factors that influence the age dependence of radiation risks, including susceptibility, expression and latency, and radiation quality. These factors depend not only on the individual s age, but also their genetic sensitivity and interaction with other environmental factors. Epidemiological data is limited in describing the age dependence on risk. The 2005, BEIR VII report recommends an age dependence for cancer risk attributable solely to the life-table disagreeing strongly with the NCRP model. However, BEIR VII also noted the limited power of human data for concomitantly describing both age and age after exposure dependences of cancer risks. Many experimental studies have shown that high LET radiation (e.g., high charge and energy (HZE) nuclei and neutrons) display reduced latency compared to low LET radiation, suggesting distinct biological

  5. Lassa Fever in Post-Conflict Sierra Leone

    PubMed Central

    Hartnett, Jessica N.; Levy, Danielle C.; Yenni, Rachael E.; Moses, Lina M.; Fullah, Mohammed; Momoh, Mambo; Fonnie, Mbalu; Fonnie, Richard; Kanneh, Lansana; Koroma, Veronica J.; Kargbo, Kandeh; Ottomassathien, Darin; Muncy, Ivana J.; Jones, Abigail B.; Illick, Megan M.; Kulakosky, Peter C.; Haislip, Allyson M.; Bishop, Christopher M.; Elliot, Deborah H.; Brown, Bethany L.; Zhu, Hu; Hastie, Kathryn M.; Andersen, Kristian G.; Gire, Stephen K.; Tabrizi, Shervin; Tariyal, Ridhi; Stremlau, Mathew; Matschiner, Alex; Sampey, Darryl B.; Spence, Jennifer S.; Cross, Robert W.; Geisbert, Joan B.; Folarin, Onikepe A.; Happi, Christian T.; Pitts, Kelly R.; Geske, F. Jon; Geisbert, Thomas W.; Saphire, Erica Ollmann; Robinson, James E.; Wilson, Russell B.; Sabeti, Pardis C.; Henderson, Lee A.; Khan, S. Humarr; Bausch, Daniel G.; Branco, Luis M.; Garry, Robert F.

    2014-01-01

    Background Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Methodology/Principal Findings Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Conclusions/Significance Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to

  6. Probabilistic Multilocus Haplotype Reconstruction in Outcrossing Tetraploids.

    PubMed

    Zheng, Chaozhi; Voorrips, Roeland E; Jansen, Johannes; Hackett, Christine A; Ho, Julie; Bink, Marco C A M

    2016-05-01

    For both plant (e.g., potato) and animal (e.g., salmon) species, unveiling the genetic architecture of complex traits is key to the genetic improvement of polyploids in agriculture. F1 progenies of a biparental cross are often used for quantitative trait loci (QTL) mapping in outcrossing polyploids, where haplotype reconstruction by identifying the parental origins of marker alleles is necessary. In this paper, we build a novel and integrated statistical framework for multilocus haplotype reconstruction in a full-sib tetraploid family from biallelic marker dosage data collected from single-nucleotide polymorphism (SNP) arrays or next-generation sequencing technology given a genetic linkage map. Compared to diploids, in tetraploids, additional complexity needs to be addressed, including double reduction and possible preferential pairing of chromosomes. We divide haplotype reconstruction into two stages: parental linkage phasing for reconstructing the most probable parental haplotypes and ancestral inference for probabilistically reconstructing the offspring haplotypes conditional on the reconstructed parental haplotypes. The simulation studies and the application to real data from potato show that the parental linkage phasing is robust to, and that the subsequent ancestral inference is accurate for, complex chromosome pairing behaviors during meiosis, various marker segregation types, erroneous genetic maps except for long-range disturbances of marker ordering, various amounts of offspring dosage errors (up to ∼20%), and various fractions of missing data in parents and offspring dosages. PMID:26920758

  7. AGE-DEPENDENT DIFFERENCES IN THE SUSCEPTIBILITY OF RATS TO DELTAMETHRIN

    EPA Science Inventory

    Separate groups of weanling and adult rats were exposed to both behaviorally-active and lethal doses of deltamethrin to examine age-dependent toxicity of a pyrethroid over a wide dose range. he acoustic startle response (ASR) was selected for comparison at low doses since it is a...

  8. Molecular Correlates of Age-Dependent Seizures in an Inherited Neonatal-Infantile Epilepsy

    ERIC Educational Resources Information Center

    Liao, Yunxiang; Deprez, Liesbet; Maljevic, Snezana; Pitsch, Julika; Claes, Lieve; Hristova, Dimitrina; Jordanova, Albena; Ala-Mello, Sirpa; Bellan-Koch, Astrid; Blazevic, Dragica; Schubert, Simone; Thomas, Evan A.; Petrou, Steven; Becker, Albert J.; De Jonghe, Peter; Lerche, Holger

    2010-01-01

    Many idiopathic epilepsy syndromes have a characteristic age dependence, the underlying molecular mechanisms of which are largely unknown. Here we propose a mechanism that can explain that epileptic spells in benign familial neonatal-infantile seizures occur almost exclusively during the first days to months of life. Benign familial…

  9. Age-dependent seizures of absence epilepsy and sleep spindles dynamics in WAG/Rij rats

    NASA Astrophysics Data System (ADS)

    Grubov, Vadim V.; Sitnikova, Evgenia Y.; Pavlov, Alexey N.; Khramova, Marina V.; Koronovskii, Alexey A.; Hramov, Alexander E.

    2015-03-01

    In the given paper, a relation between time-frequency characteristics of sleep spindles and the age-dependent epileptic activity in WAG/Rij rats is discussed. Analysis of sleep spindles based on the continuous wavelet transform is performed for rats of different ages. It is shown that the epileptic activity affects the time-frequency intrinsic dynamics of sleep spindles.

  10. Age-dependent changes in the neural substrates of empathy in autism spectrum disorder.

    PubMed

    Schulte-Rüther, Martin; Greimel, Ellen; Piefke, Martina; Kamp-Becker, Inge; Remschmidt, Helmut; Fink, Gereon R; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2014-08-01

    In typical development, empathic abilities continue to refine during adolescence and early adulthood. Children and adolescents with autism spectrum disorders (ASD) show deficits in empathy, whereas adults with ASD may have developed compensatory strategies. We aimed at comparing developmental trajectories in the neural mechanisms underlying empathy in individuals with ASD and typically developing control (TDC) subjects. Using an explicit empathizing paradigm and functional magnetic resonance imaging, 27 participants with ASD and 27 TDC aged 12-31 years were investigated. Participants were asked to empathize with emotional faces and to either infer the face's emotional state (other-task) or to judge their own emotional response (self-task). Differential age-dependent changes were evident during the self-task in the right dorsolateral prefrontal cortex, right medial prefrontal cortex, right inferior parietal cortex, right anterior insula and occipital cortex. Age-dependent decreases in neural activation in TDC were paralleled by either increasing or unchanged age-dependent activation in ASD. These data suggest ASD-associated deviations in the developmental trajectories of self-related processing during empathizing. In TDC, age-dependent modulations of brain areas may reflect the 'fine-tuning' of cortical networks by reduction of task-unspecific brain activity. Increased age-related activation in individuals with ASD may indicate the development of compensatory mechanisms. PMID:23784073

  11. AGE DEPENDENT MODEL OF PCB IN A LAKE MICHIGAN FOOD CHAIN

    EPA Science Inventory

    An age-dependent food chain model that considers species bioenergetics and toxicant exposure through water and food was developed. It was successfully applied to PCB contamination in the Lake Michigan lake trout food chain represented by phytoplankton, Mysis, alewife, and lake tr...

  12. Paradise Lost: Age-Dependent Mortality of American Communes, 1609-1965

    ERIC Educational Resources Information Center

    Kitts, James A.

    2009-01-01

    Theorists agree that the risk of folding changes as organizations age, but there is little consensus as to the general form or generative processes of age-dependent mortality. This article investigates four such processes (maturation, senescence, legitimation and obsolescence), which have been taken as competing accounts. Using two analytical…

  13. Age-dependent modulation of the somatosensory network upon eye closure.

    PubMed

    Brodoehl, Stefan; Klingner, Carsten; Witte, Otto W

    2016-02-01

    Eye closure even in complete darkness can improve somatosensory perception by switching the brain to a uni-sensory processing mode. This causes an increased information flow between the thalamus and the somatosensory cortex while decreasing modulation by the visual cortex. Previous work suggests that these modulations are age-dependent and that the benefit in somatosensory performance due to eye closing diminishes with age. The cause of this age-dependency and to what extent somatosensory processing is involved remains unclear. Therefore, we intended to characterize the underlying age-dependent modifications in the interaction and connectivity of different sensory networks caused by eye closure. We performed functional MR-imaging with tactile stimulation of the right hand under the conditions of opened and closed eyes in healthy young and elderly participants. Conditional Granger causality analysis was performed to assess the somatosensory and visual networks, including the thalamus. Independent of age, eye closure improved the information transfer from the thalamus to and within the somatosensory cortex. However, beyond that, we found an age-dependent recruitment strategy. Whereas young participants were characterized by an optimized information flow within the relays of the somatosensory network, elderly participants revealed a stronger modulatory influence of the visual network upon the somatosensory cortex. Our results demonstrate that the modulation of the somatosensory and visual networks by eye closure diminishes with age and that the dominance of the visual system is more pronounced in the aging brain. PMID:26546882

  14. Ontogenetic changes in genetic variances of age-dependent plasticity along a latitudinal gradient.

    PubMed

    Nilsson-Örtman, V; Rogell, B; Stoks, R; Johansson, F

    2015-10-01

    The expression of phenotypic plasticity may differ among life stages of the same organism. Age-dependent plasticity can be important for adaptation to heterogeneous environments, but this has only recently been recognized. Whether age-dependent plasticity is a common outcome of local adaptation and whether populations harbor genetic variation in this respect remains largely unknown. To answer these questions, we estimated levels of additive genetic variation in age-dependent plasticity in six species of damselflies sampled from 18 populations along a latitudinal gradient spanning 3600 km. We reared full sib larvae at three temperatures and estimated genetic variances in the height and slope of thermal reaction norms of body size at three points in time during ontogeny using random regression. Our data show that most populations harbor genetic variation in growth rate (reaction norm height) in all ontogenetic stages, but only some populations and ontogenetic stages were found to harbor genetic variation in thermal plasticity (reaction norm slope). Genetic variances in reaction norm height differed among species, while genetic variances in reaction norm slope differed among populations. The slope of the ontogenetic trend in genetic variances of both reaction norm height and slope increased with latitude. We propose that differences in genetic variances reflect temporal and spatial variation in the strength and direction of natural selection on growth trajectories and age-dependent plasticity. Selection on age-dependent plasticity may depend on the interaction between temperature seasonality and time constraints associated with variation in life history traits such as generation length. PMID:25649500

  15. Age-dependent cognitive impairment in a Drosophila Fragile X model and its pharmacological rescue

    PubMed Central

    Choi, Catherine H.; Schoenfeld, Brian P.; Liebelt, David A.; Ferreiro, David; Ferrick, Neal J.; Hinchey, Paul; Kollaros, Maria; Rudominer, Rebecca L.; Terlizzi, Allison M.; Koenigsberg, Eric; Wang, Yan; Sumida, Ai; Nguyen, Hanh T.; Bell, Aaron J.; McDonald, Thomas V.

    2010-01-01

    Fragile X syndrome afflicts 1 in 2,500 individuals and is the leading heritable cause of mental retardation worldwide. The overriding clinical manifestation of this disease is mild to severe cognitive impairment. Age-dependent cognitive decline has been identified in Fragile X patients, although it has not been fully characterized nor examined in animal models. A Drosophila model of this disease has been shown to display phenotypes bearing similarity to Fragile X symptoms. Most notably, we previously identified naive courtship and memory deficits in young adults with this model that appear to be due to enhanced metabotropic glutamate receptor (mGluR) signaling. Herein we have examined age-related cognitive decline in the Drosophila Fragile X model and found an age-dependent loss of learning during training. We demonstrate that treatment with mGluR antagonists or lithium can prevent this age-dependent cognitive impairment. We also show that treatment with mGluR antagonists or lithium during development alone displays differential efficacy in its ability to rescue naive courtship, learning during training and memory in aged flies. Furthermore, we show that continuous treatment during aging effectively rescues all of these phenotypes. These results indicate that the Drosophila model recapitulates the age-dependent cognitive decline observed in humans. This places Fragile X in a category with several other diseases that result in age-dependent cognitive decline. This demonstrates a role for the Drosophila Fragile X Mental Retardation Protein (dFMR1) in neuronal physiology with regard to cognition during the aging process. Our results indicate that misregulation of mGluR activity may be causative of this age onset decline and strengthens the possibility that mGluR antagonists and lithium may be potential pharmacologic compounds for counteracting several Fragile X symptoms. PMID:20039205

  16. Response to the Ebola crisis in Sierra Leone.

    PubMed

    Davies, Beauty Chiedza; Bowley, Douglas; Roper, Katrina

    2015-02-27

    The Ebola outbreak in 2014 marked the first time that an epidemic of this viral haemorrhagic fever had occurred in West Africa. From its origin in Guinea, the outbreak rapidly increased to become a humanitarian crisis affecting all aspects of life in the three countries worst affected: Guinea, Sierra Leone and Liberia. Improving understanding of Ebola virus disease among the general population and instigating the behavioural changes required to help break the epidemic were central to the public health response. This article explores some of the misconceptions about Ebola as it spread into Sierra Leonean communities, and the social mobilisation response of the government of Sierra Leone. It is a reflective account of conversations with Sierra Leonean nationals during a military deployment at the International Security Advisory Team headquarters medical treatment facility in Freetown. PMID:25711592

  17. Sequence Variability and Geographic Distribution of Lassa Virus, Sierra Leone

    PubMed Central

    Stockelman, Michael G.; Moses, Lina M.; Park, Matthew; Stenger, David A.; Ansumana, Rashid; Bausch, Daniel G.; Lin, Baochuan

    2015-01-01

    Lassa virus (LASV) is endemic to parts of West Africa and causes highly fatal hemorrhagic fever. The multimammate rat (Mastomys natalensis) is the only known reservoir of LASV. Most human infections result from zoonotic transmission. The very diverse LASV genome has 4 major lineages associated with different geographic locations. We used reverse transcription PCR and resequencing microarrays to detect LASV in 41 of 214 samples from rodents captured at 8 locations in Sierra Leone. Phylogenetic analysis of partial sequences of nucleoprotein (NP), glycoprotein precursor (GPC), and polymerase (L) genes showed 5 separate clades within lineage IV of LASV in this country. The sequence diversity was higher than previously observed; mean diversity was 7.01% for nucleoprotein gene at the nucleotide level. These results may have major implications for designing diagnostic tests and therapeutic agents for LASV infections in Sierra Leone. PMID:25811712

  18. Home birth and hospital birth trends in Bo, Sierra Leone.

    PubMed

    Jacobsen, Kathryn H; Abdirahman, Hafsa A; Ansumana, Rashid; Bockarie, Alfred S; Bangura, Umaru; Jimmy, David Henry; Malanoski, Anthony P; Sundufu, Abu James; Stenger, David A

    2012-06-01

    As of April 2010, all maternity care at government healthcare facilities in Sierra Leone is provided at no cost to patients. In late 2010, we conducted a community health census of 18 sections of the city of Bo (selected via randomized cluster sampling from 68 total sections). Among the 3421 women with a history of pregnancy who participated in the study, older women most often reported having a history of both home and hospital deliveries, while younger women showed a preference for hospital births. The proportion of lastborn children delivered at a healthcare facility increased from 71.8% of offspring 10-14 years old to 81.1% of those one to nine years old and 87.3% of infants born after April 2010. These findings suggest that the new maternal healthcare initiative has accelerated an existing trend toward a preference for healthcare facility births, at least in some urban parts of Sierra Leone. PMID:22375565

  19. Health complications of female genital mutilation in Sierra Leone

    PubMed Central

    Bjälkander, Owolabi; Bangura, Laurel; Leigh, Bailah; Berggren, Vanja; Bergström, Staffan; Almroth, Lars

    2012-01-01

    Sierra Leone has one of the highest rates of female genital mutilation (FGM) in the world, and yet little is known about the health consequences of the practice. Purpose To explore whether and what kind of FGM-related health complications girls and women in Sierra Leone experience, and to elucidate their health care-seeking behaviors. Patients and methods A feasibility study was conducted to test and refine questionnaires and methods used for this study. Thereafter, a cross-section of girls and women (n = 258) attending antenatal care and Well Women Clinics in Bo Town, Bo District, in the southern region and in Makeni Town, Bombali District, in the northern region of Sierra Leone were randomly selected. Participants answered interview-administrated pretested structured questionnaires with open- ended-questions, administrated by trained female personnel. Results All respondents had undergone FGM, most between 10 and 14 years of age. Complications were reported by 218 respondents (84.5%), the most common ones being excessive bleeding, delay in or incomplete healing, and tenderness. Fever was significantly more often reported by girls who had undergone FGM before 10 years of age compared with those who had undergone the procedure later. Out of those who reported complications, 187 (85.8%) sought treatment, with 89 of them visiting a traditional healer, 75 a Sowei (traditional circumciser), and 16 a health professional. Conclusion The high prevalence rate of FGM and the proportion of medical complications show that FGM is a matter for public health concern in Sierra Leone. Girls who undergo FGM before 10 years of age seem to be more vulnerable to serious complications than those who are older at the time of FGM. It is important that health care personnel are aware of, and look for possible complications from FGM, and encourage girls and women to seek medical care for their problems. PMID:22870046

  20. Methodology for stormwater runoff investigation, urban Leon County, Florida

    USGS Publications Warehouse

    Franklin, M.A.

    1982-01-01

    The U.S. Geological Survey in cooperation with Leon County is currently (1981) developing a lumped-parameter, rainfall-runoff model for the urban area of the county. Flood information from 16 sites is being collected and will be analyzed to define hydrologic relations useful for estimating magnitude and frequency of discharges in urban areas. This report summarizes methods of collection, processing, and analysis of rainfall-runoff data from the drainage basins that will be used in the model.

  1. Age dependence of metals in hair in a selected US population

    SciTech Connect

    Paschal, D.C.; DiPietro, E.S.; Phillips, D.L.; Gunter, E.W. )

    1989-02-01

    Concentrations of 28 metals were determined in hair samples from 199 children (age {le} years) and 322 adults (age 13-73) years. Levels of calcium, barium, magnesium, zinc, and strontium all show a similar age-dependent increase up to about 12-14 years; levels of aluminum show a decrease with age. Relationships of elemental concentrations with age were examined by using correlation, linear regression, t tests, and discriminant analysis. Statistically significant differences in mean concentration values between children and adults were shown for these metals. Discriminant analysis gave about 95% accuracy in classifying a test data set into the categories of children and adults. A hypothesis suggested by the data is that there is an age-dependent excretion in hair of alkali metals during skeletal growth and development. The observed decrease in aluminum is largely unexplained at this time.

  2. Influence of nootropic drugs on the age-dependent potassium-coupling of transmitter release.

    PubMed

    Wustmann, C; Blaschke, M; Rudolph, E; Fischer, H D; Schmidt, J

    1990-01-01

    The potassium-induced dopamine release from rat striatum slices shows an age-dependent decline comparable to observations after hypoxia. Pretreatment of aged animals with antihypoxically active nootropic drugs for three weeks results in an improvement of the impaired transmitter release. Simultaneously the slope of the stimulus-release relation is increased and an age-related 50% decrease of the high affinity Ca(++)-ATPase activity (brain P2 fraction) is partially compensated. Like the antihypoxic effect, the effectiveness of nootropic drugs regarding age-dependent changes of neuronal functions probably will consist, above all, in vascular influences of the microcirculation, repair of phospholipids damaged by free radical triggered peroxidation and improvement of stimulus-release coupling. PMID:2149265

  3. Age dependence of the concentrations of harmful substances in Baltic herring (Clupea harengus)

    SciTech Connect

    Perttila, M.; Tervo, V.; Parmanne, R.

    1982-01-01

    The age dependence of Zn, Cu, Pb, Cd, Hg, CH/sub 3/-Hg, DDT, DDD, DDE, HCH, HCB and the PCBs have been studied in Baltic herring of 1 to 6 years of age. Lead, cadmium, mercury and the organochlorine concentrations increase significantly with age. In the case of the DDTs and the PCBs, the variations can be attributed almost totally to the combined effect of age and variations in the lipid percentage.

  4. Optimal Control of Markov Processes with Age-Dependent Transition Rates

    SciTech Connect

    Ghosh, Mrinal K. Saha, Subhamay

    2012-10-15

    We study optimal control of Markov processes with age-dependent transition rates. The control policy is chosen continuously over time based on the state of the process and its age. We study infinite horizon discounted cost and infinite horizon average cost problems. Our approach is via the construction of an equivalent semi-Markov decision process. We characterise the value function and optimal controls for both discounted and average cost cases.

  5. Age-Dependent Pancreatic Gene Regulation Reveals Mechanisms Governing Human β Cell Function.

    PubMed

    Arda, H Efsun; Li, Lingyu; Tsai, Jennifer; Torre, Eduardo A; Rosli, Yenny; Peiris, Heshan; Spitale, Robert C; Dai, Chunhua; Gu, Xueying; Qu, Kun; Wang, Pei; Wang, Jing; Grompe, Markus; Scharfmann, Raphael; Snyder, Michael S; Bottino, Rita; Powers, Alvin C; Chang, Howard Y; Kim, Seung K

    2016-05-10

    Intensive efforts are focused on identifying regulators of human pancreatic islet cell growth and maturation to accelerate development of therapies for diabetes. After birth, islet cell growth and function are dynamically regulated; however, establishing these age-dependent changes in humans has been challenging. Here, we describe a multimodal strategy for isolating pancreatic endocrine and exocrine cells from children and adults to identify age-dependent gene expression and chromatin changes on a genomic scale. These profiles revealed distinct proliferative and functional states of islet α cells or β cells and histone modifications underlying age-dependent gene expression changes. Expression of SIX2 and SIX3, transcription factors without prior known functions in the pancreas and linked to fasting hyperglycemia risk, increased with age specifically in human islet β cells. SIX2 and SIX3 were sufficient to enhance insulin content or secretion in immature β cells. Our work provides a unique resource to study human-specific regulators of islet cell maturation and function. PMID:27133132

  6. Age-dependent tissue-specific exposure of cell phone users

    NASA Astrophysics Data System (ADS)

    Christ, Andreas; Gosselin, Marie-Christine; Christopoulou, Maria; Kühn, Sven; Kuster, Niels

    2010-04-01

    The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.

  7. RTEMS SMP and MTAPI for Efficient Multi-Core Space Applications on LEON3/LEON4 Processors

    NASA Astrophysics Data System (ADS)

    Cederman, Daniel; Hellstrom, Daniel; Sherrill, Joel; Bloom, Gedare; Patte, Mathieu; Zulianello, Marco

    2015-09-01

    This paper presents the final result of an European Space Agency (ESA) activity aimed at improving the software support for LEON processors used in SMP configurations. One of the benefits of using a multicore system in a SMP configuration is that in many instances it is possible to better utilize the available processing resources by load balancing between cores. This however comes with the cost of having to synchronize operations between cores, leading to increased complexity. While in an AMP system one can use multiple instances of operating systems that are only uni-processor capable, a SMP system requires the operating system to be written to support multicore systems. In this activity we have improved and extended the SMP support of the RTEMS real-time operating system and ensured that it fully supports the multicore capable LEON processors. The targeted hardware in the activity has been the GR712RC, a dual-core core LEON3FT processor, and the functional prototype of ESA's Next Generation Multiprocessor (NGMP), a quad core LEON4 processor. The final version of the NGMP is now available as a product under the name GR740. An implementation of the Multicore Task Management API (MTAPI) has been developed as part of this activity to aid in the parallelization of applications for RTEMS SMP. It allows for simplified development of parallel applications using the task-based programming model. An existing space application, the Gaia Video Processing Unit, has been ported to RTEMS SMP using the MTAPI implementation to demonstrate the feasibility and usefulness of multicore processors for space payload software. The activity is funded by ESA under contract 4000108560/13/NL/JK. Gedare Bloom is supported in part by NSF CNS-0934725.

  8. An Arabidopsis haplotype map takes root

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Laying the foundation for an A. thaliana haplotype map, Clark et al.1 conducted a thorough array resequencing of 20 diverse A. thaliana genomes at single-base resolution. This provided a powerful catalog of genetic diversity, with more than 1 million SNPs and hypervariable regions (50-bp to >10-kb d...

  9. Applications of haplotypes in dairy farm management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Haplotypes from genomic tests are now available for almost 100,000 dairy cows and heifers in the U.S.. Genomic EBV values are accelerating the rate of genetic improvement in dairy cattle, but genomic information also is useful for making improved decisions on the farm. Mate selection strategies have...

  10. Dissecting risk haplotypes in sporadic Alzheimer's disease.

    PubMed

    Soldner, Frank; Jaenisch, Rudolf

    2015-04-01

    Understanding how genetic risk variants contribute to complex diseases is crucial for predicting disease susceptibility and developing patient-tailored therapies. In this issue of Cell Stem Cell, Young et al. (2015) dissect the function of common non-coding risk haplotypes in the SORL1 locus in the pathogenesis of sporadic Alzheimer's disease using patient-derived induced pluripotent stem cells. PMID:25842969

  11. Evaluating the Feasibility of Fitting Haplotype Effects as Random: Variance Component Estimation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fitting haplotypes as random effects in association studies may prevent overestimation of haplotypic effects with low frequencies. The objective was to determine whether haplotypic variance could be accurately estimated. Using simulation, haplotypic effects were deterministically assigned to eithe...

  12. Non-Governmental Organizations in Africa: The Leonenet Street Children Project in Sierra Leone

    ERIC Educational Resources Information Center

    Hinton, Samuel

    2005-01-01

    The purpose of this paper is to provide snapshots of observations, interventions, and processes in the day to day working of a child charity in Sierra Leone. There were 114 local and 49 overseas funded Non Governmental Organizations (NGOs) in Sierra Leone in 2002. The Leonenet Street Children Project was founded in 1996 by the membership of the…

  13. Assessment of Anemia Knowledge, Attitudes and Behaviors among Pregnant Women in Sierra Leone

    ERIC Educational Resources Information Center

    M'Cormack, Fredanna A. D.; Drolet, Judy C.

    2012-01-01

    Introduction: Iron deficiency anemia prevalence of pregnant Sierra Leone women currently is reported to be 59.7%. Anemia is considered to be a direct cause of 3-7% of maternal deaths and an indirect cause of 20-40% of maternal deaths. This study explores knowledge, attitudes, and behaviors of urban pregnant Sierra Leone women regarding anemia.…

  14. Curriculum Diversification Re-examined--A Case Study of Sierra Leone.

    ERIC Educational Resources Information Center

    Wright, Cream A. H.

    This paper deals with a case study of secondary curriculum diversification as a vocationalization strategy in Sierra Leone. It explores diversification issues from four crucial standpoints that are distinct but highly interrelated. First, diversification is dealt with as a policy that was adopted and actively pursued by Sierra Leone for over a…

  15. The role of heat shock protein 70 in mediating age-dependent mortality in sepsis.

    PubMed

    McConnell, Kevin W; Fox, Amy C; Clark, Andrew T; Chang, Nai-Yuan Nicholas; Dominguez, Jessica A; Farris, Alton B; Buchman, Timothy G; Hunt, Clayton R; Coopersmith, Craig M

    2011-03-15

    Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6- to 12-wk-old) and aged (16- to 17-mo-old) HSP70(-/-) and wild-type (WT) mice to determine whether HSP70 modulated outcome in an age-dependent fashion. Young HSP70(-/-) and WT mice subjected to cecal ligation and puncture, Pseudomonas aeruginosa pneumonia, or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70(-/-) mice than aged WT mice subjected to cecal ligation and puncture (p = 0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared with WT mice, aged septic HSP70(-/-) mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70(-/-) mice had increased systemic levels of TNF-α, IL-6, IL-10, and IL-1β compared with WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged, but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation. PMID:21296977

  16. The role of HSP70 in mediating age-dependent mortality in sepsis

    PubMed Central

    McConnell, Kevin W.; Fox, Amy C.; Clark, Andrew T.; Chang, Nai-Yuan Nicholas; Dominguez, Jessica A.; Farris, Alton B.; Buchman, Timothy G.; Hunt, Clayton R.; Coopersmith, Craig M.

    2011-01-01

    Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6–12week old) and aged (16–17 month old) HSP70−/− and wild type (WT) mice to determine if HSP70 modulated outcome in an age-dependent fashion. Young HSP70−/− and WT mice subjected to cecal ligation and puncture (CLP), Pseudomonas aeruginosa pneumonia or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70−/− mice than aged WT mice subjected to CLP (p=0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared to WT mice, aged septic HSP70−/− mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70−/−mice had increased systemic levels of TNF-α, IL-6, IL-10 and IL-1β compared to WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation. PMID:21296977

  17. Age-Dependent Neuroimmune Modulation of IGF-1R in the Traumatic Mice

    PubMed Central

    2012-01-01

    Background Age-dependent neuroimmune modulation following traumatic stress is accompanied by discordant upregulation of Fyn signaling in the frontal cortex, but the mechanistic details of the potential cellular behavior regarding IGF-1R/Fyn have not been established. Methods Trans-synaptic IGF-1R signaling during the traumatic stress was comparably examined in wild type, Fyn (−/−) and MOR (−/−) mice. Techniques included primary neuron culture, in vitro kinase activity, immunoprecipitation, Western Blot, sucrose discontinuous centrifugation. Besides that, [3 H] incorporation was used to assay lymphocyte proliferation and NK cell activity. Results We demonstrate robust upregulation of synaptic Fyn activity following traumatic stress, with higher amplitude in 2-month mice than that in 1-year counterpart. We also established that the increased Fyn signaling is accompanied by its molecular connection with IGF-1R within the synaptic zone. Detained analysis using Fyn (−/−) and MOR (−/−) mice reveal that IGF-1R/Fyn signaling is governed to a large extent by mu opioid receptor (MOR), and with age-dependent manner; these signaling cascades played a central role in the modulation of lymphocyte proliferation and NK cell activity. Conclusions Our data argued for a pivotal role of synaptic IGF-1R/Fyn signaling controlled by MOR downstream signaling cascades were crucial for the age-dependent neuroimmune modulation following traumatic stress. The result here might present a new quality of synaptic cellular communication governing the stress like events and have significant potential for the development of therapeutic approaches designed to minimize the heightened vulnerability during aging. PMID:22640633

  18. Mutant Alpha-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain

    PubMed Central

    Yang, Weili; Wang, Guohao; Wang, Chuan-En; Guo, Xiangyu; Yin, Peng; Gao, Jinquan; Tu, Zhuchi; Wang, Zhengbo; Wu, Jing; Hu, Xintian; Li, Shihua

    2015-01-01

    Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2–3, 7–8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD. PMID:26019347

  19. Age-dependent loss of the C-terminal amino acid from alpha crystallin

    NASA Technical Reports Server (NTRS)

    Emmons, T.; Takemoto, L.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    Antiserum made against the C-terminal region of alpha-A crystallin was used to monitor the purification of a tryptic peptide containing the C-terminus of the molecule from fetal versus adult bovine lenses. Mass spectral analysis of the peptide preparations obtained from these lenses demonstrated the presence of a peptide (T20) containing an intact C-terminus from fetal lenses and the presence of an additional peptide (T20') from older lenses that contained a cleaved C-terminal serine. These results demonstrate an age-dependent processing of alpha-A crystallin in the bovine lens, resulting in removal of the C-terminal amino acid residue.

  20. Haplotype reconstruction and estimation of haplotype frequencies from nuclear families with only one parent available.

    PubMed

    Ding, Xiangdong; Zhang, Qin; Flury, Christine; Simianer, Henner

    2006-01-01

    Recent literature has suggested that haplotype inference through close relatives, especially from nuclear families can be an alternative strategy in determining the linkage phase. In this paper, haplotype reconstruction and estimation of haplotype frequencies via expectation maximization (EM) algorithm including nuclear families with only one parent available is proposed. Parent and his (her) child are treated as parent-child pair with one shared haplotype. This reduces the number of potential haplotype pairs for both parent and child separately, resulting in a higher accuracy of the estimation. In a series of simulations, the comparisons of PHASE, GENEHUNTER, EM-based approach for complete nuclear families and our approach are carried out. In all situations, EM-based approach for trio data is comparable but slightly worse error rate than PHASE, our approach is slightly better and much faster than PHASE for incomplete trios, the performance of GENEHUNTER is very bad in simple nuclear family settings and dramatically decreased with the number of markers being increased. On the other hand, the comparison result of different sampling designs demonstrates that sampling trios is the most efficient design to estimate haplotype frequencies in populations under same genotyping cost. PMID:16954697

  1. Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

    PubMed Central

    Zinnanti, William J.; Lazovic, Jelena; Housman, Cathy; LaNoue, Kathryn; O’Callaghan, James P.; Simpson, Ian; Woontner, Michael; Goodman, Stephen I.; Connor, James R.; Jacobs, Russell E.; Cheng, Keith C.

    2007-01-01

    Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I. PMID:17932566

  2. Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle

    NASA Technical Reports Server (NTRS)

    Adams, Gregory R.; Baldwin, Kenneth M.

    1995-01-01

    This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid (creatine depletion juvenile (CDJ) group). Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens (normal diet adult and creatine depletion adult (CDA) groups). After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC ditribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC tranitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of the animals to be used.

  3. Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I.

    PubMed

    Zinnanti, William J; Lazovic, Jelena; Housman, Cathy; LaNoue, Kathryn; O'Callaghan, James P; Simpson, Ian; Woontner, Michael; Goodman, Stephen I; Connor, James R; Jacobs, Russell E; Cheng, Keith C

    2007-11-01

    Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I. PMID:17932566

  4. Probiotic Mixture KF Attenuates Age-Dependent Memory Deficit and Lipidemia in Fischer 344 Rats.

    PubMed

    Jeong, Jin-Ju; Kim, Kyung-Ah; Ahn, Young-Tae; Sim, Jae-Hun; Woo, Jae-Yeon; Huh, Chul-Sung; Kim, Dong-Hyun

    2015-09-01

    To investigate the memory-enhancing effect of lactic acid bacteria, we selected the probiotic mixture KF, which consisted of Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 (1 × 10(11) CFU/g of each strain), and investigated its antilipidemic and memoryenhancing effects in aged Fischer 344 rats. KF (1 × 10(10) CFU/rat/day), which was administered orally once a day (6 days per week) for 8 weeks, significantly inhibited age-dependent increases of blood triglyceride and reductions of HDL cholesterol (p < 0.05). KF restored agereduced spontaneous alternation in the Y-maze task to 94.4% of that seen in young rats (p < 0.05). KF treatment slightly, but not significantly, shortened the escape latency daily for 4 days. Oral administration of KF restored age-suppressed doublecortin and brain-derived neurotrophic factor expression in aged rats. Orally administered KF suppressed the expression of p16, p53, and cyclooxygenase-2, the phosphorylation of Akt and mTOR, and the activation of NF-κB in the hippocampus of the brain. These findings suggest that KF may ameliorate age-dependent memory deficit and lipidemia by inhibiting NF-κB activation. PMID:25975611

  5. Experimental febrile seizures induce age-dependent structural plasticity and improve memory in mice.

    PubMed

    Tao, K; Ichikawa, J; Matsuki, N; Ikegaya, Y; Koyama, R

    2016-03-24

    Population-based studies have demonstrated that children with a history of febrile seizure (FS) perform better than age-matched controls at hippocampus-dependent memory tasks. Here, we report that FSs induce two distinct structural reorganizations in the hippocampus and bidirectionally modify future learning abilities in an age-dependent manner. Compared with age-matched controls, adult mice that had experienced experimental FSs induced by hyperthermia (HT) on postnatal day 14 (P14-HT) performed better in a cognitive task that requires dentate granule cells (DGCs). The enhanced memory performance correlated with an FS-induced persistent increase in the density of large mossy fiber terminals (LMTs) of the DGCs. The memory enhancement was not observed in mice that had experienced HT-induced seizures at P11 which exhibited abnormally located DGCs in addition to the increased LMT density. The ectopic DGCs of the P11-HT mice were abolished by the diuretic bumetanide, and this pharmacological treatment unveiled the masked memory enhancement. Thus, this work provides a novel basis for age-dependent structural plasticity in which FSs influence future brain function. PMID:26794590

  6. Age dependence of the chemical composition of stars in globular clusters

    NASA Astrophysics Data System (ADS)

    Kipper, T.

    An overview of recent investigations of the age dependence of the chemical composition of stars in globular clusters is presented. Attention is given to two contradictory hypotheses on the issue of cluster age and metallicity. According to Carney (1980), there is a metallicity-age dependence. According to Gratton (1985), all globular clusters are the same age - approximately 16 x 10 exp 9 years old. The metallicity of the most metal-abundant clusters is discussed. The Fe/H metallicity of the object 47 Tuc is determined to range from -1.1 to -0.4. The chemical homogeneity of clusters is examined. Spectral investigations of NGC 6752 stars from the main sequence up to the upper part of the giants' branch did not show Fe/H dispersion. The study by Cohen (1980) of the relative distribution of heavy elements in clusters of different metallicity show that in spite of the significant difference in Fe/H (up to 2.0 dex) the relative abundances are quite similar.

  7. Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent.

    PubMed

    Podlasek, Carol A; Ghosh, Rudrani; Onur Cakir, Omer; Bond, Christopher; McKenna, Kevin E; McVary, Kevin T

    2013-11-01

    Benign prostatic hyperplasia (BPH) is a serious health concern and is an underlying cause of lower urinary tract symptoms (LUTS) in many men. In affected men, LUTS/BPH is believed to result from benign proliferation of the prostate resulting in bladder outlet obstruction. Postnatal growth of the prostate is controlled via growth factor and endocrine mechanisms. However, little attention had been given to the function of the autonomic nervous system in prostate growth and differentiation. Nerve growth factor (NGF) is a prostatic mitogen that has a trophic role in autonomic sensory end organ interaction. In this study, we examine how the autonomic nervous system influences prostate growth as a function of age by quantifying NGF in the rat ventral prostate (VP) after pelvic ganglionectomy. Unilateral pelvic ganglionectomy was performed on postnatal days 30 (P30), 60 and 120 Sprague-Dawley rats in comparison to sham controls (n=39). Semiquantitative RT-PCR, Western blotting and immunohistochemical analysis for NGF were performed on denervated, intact (contralateral side) and sham control VP 7 days after surgery. Ngf RNA expression was significantly increased in the denervated and intact hyperplastic VP. Western blotting showed age-dependent increases in NGF protein at P60 in the contralateral intact VP. NGF was localized in the nerves, basal cells and columnar epithelium of the prostatic ducts. Denervation causes age-dependent increases in NGF in the VP, which is a potential mechanism by which the autonomic nervous system may regulate prostate growth and lead to BPH/LUTS. PMID:23872662

  8. REDOX RESPONSIVE TRANSCRIPTION FACTOR1 is involved in age-dependent and systemic stress signaling

    PubMed Central

    Matsuo, Mitsuhiro; Oelmüller, Ralf

    2015-01-01

    REDOX RESPONSIVE TRANSCRIPTION FACTOR1 (RRTF1) regulates redox homeostasis under stress, however the mechanism is mainly unknown. In a recent publication, we analyzed rrtf1 knockout (ko) and RRTF1 overexpressor lines of Arabidopsis thaliana and showed that RRTF1 plays a crucial role in reactive oxygen species (ROS) production. Ko line produces less and overexpressor lines constitutively high levels of ROS under stress, and the amount of ROS increases with increase in stress and the RRTF1 level in the plant. The transcription factor also activates systemic ROS signaling under stress.1 In this report, we show that RRTF1 exerts different roles in young and old leaves. While RRTF1 enhances defense responses to high light (HL) stress in young leaves, it induces senescence and chlorosis in older leaves. These findings suggest that RRTF1 and/or RRTF1-mediated ROS signaling induce stress responses in an age-dependent manner, and the age-dependent alteration in the RRTF1 function might be important for plants' acclimation to the stress environment. PMID:26479402

  9. REMEDIATION OF LEON WATER FLOOD, BUTLER COUNTY, KANSAS

    SciTech Connect

    M.L. Korphage; Kelly Kindscher; Bruce G. Langhus

    2001-11-26

    The Leon Water Flood site has undergone one season of soil amendments and growth of specialized plants meant to colonize and accelerate the remediation of the salt-impacted site. The researchers characterized the impacted soil as to chemistry, added soil amendments, and planted several species of seedlings, and seeded the scarred areas. After the first growing season, the surface soil was again characterized and groundcover was also characterized. While plant growth was quite meager across the area, soil chemistry did improve over most of the two scars.

  10. Fighting Ebola in Sierra Leone: a view from the frontline.

    PubMed

    Owens, Stephen; Leyland, Thomas

    2016-03-01

    The largest and most complex Ebola epidemic in history is believed to have started with the infection of a 2-year-old boy in South-eastern Guinea in late 2013. Within a year, thousands of children and their families had contracted the virus, many had died and many more were orphaned. We reflect on our experiences of volunteering at the Kerry Town Ebola Treatment Centre in Sierra Leone between January and February 2015, where we were deployed to care for just a few of these children as part of the Save The Children team. PMID:26507816

  11. The Wilson disease gene: Haplotypes and mutations

    SciTech Connect

    Thomas, G.R.; Roberts, E.A.; Cox, D.W.; Walshe, J.M.

    1994-09-01

    Wilson disease (WND) is an autosomal recessive defect of copper transport. The gene involved in WND, located on chromosome 13, has recently been shown to be a putative copper transporting P-type ATPase, designated ATP7B. The gene is highly similar to ATP7A, located on the X chromosome, which is defective in Menkes disease, another disorder of copper transport. We have available for study WND families from Canada (34 families), the United Kingdom (32 families), Japan (4 families), Iceland (3 families) and Hong Kong (2 families). We have utilized four highly polymorphic CA repeat markers (D13S296, D13S301, D13S314 and D13S316) surrounding the ATP7B locus to construct haplotypes in these families. Analysis indicates that there are many unique WND haplotypes not present on normal chromosomes and that there may be a large number of different WND mutations. We have screened the WND patients for mutations in the ATP7B gene. Fifty six patients, representing all of the identified haplotypes, have been screened using single strand conformational polymorphism (SSCP), followed by selective sequencing. To date, 19 mutations and 12 polymorphisms have been identified. All of the changes are nucleotide substitutions or small insertions/deletions and there is no evidence for larger deletions as seen in the similar gene on the X chromosome, ATP7A. Haplotypes of close markers and the ability to detect some of the mutations present in the gene allow for more reliable molecular diagnosis of presymptomatic sibs of WND patients. A reassessment of individuals previously diagnosed in the presymptomatic phase is now required, as we have have identified some heterozygotes who are biochemically indistinguishable from affected homozygotes. The identification of specific mutations will soon allow direct diagnosis of WND patients with a high level of certainty.

  12. Haplotypes of angiotensinogen in essential hypertension.

    PubMed Central

    Jeunemaitre, X; Inoue, I; Williams, C; Charru, A; Tichet, J; Powers, M; Sharma, A M; Gimenez-Roqueplo, A P; Hata, A; Corvol, P; Lalouel, J M

    1997-01-01

    The M235T polymorphism of the angiotensinogen gene (AGT) has been associated with essential and pregnancy-induced hypertension. Generation of haplotypes can help to resolve whether the T235 allele itself predisposes to the development of hypertension or acts as a marker of an unknown causal molecular variant. We identified 10 diallelic polymorphisms at the AGT locus and genotyped both a series of 477 probands of hypertensive families and 364 controls, all French Caucasians, as well as a series of 92 hypertensives and 122 controls from Japan. Despite a large ethnic difference in gene frequency, a significant association of T235 with hypertension was observed both in Cancasians (.46 vs. .38, P = .004) and in Japanese (.91 vs. .76, P = .002). In both groups, the G-->A substitution located at position -6 upstream of the initial transcription site occurred at the same frequency and in complete linkage disequilibrium with the T235 allele. No other polymorphism was found to be consistently associated with hypertension. Five informative haplotypes subdividing the T235 allele were generated. Whereas two of them were associated with hypertension in Caucasians, none of these two haplotypes (H3 and H4) reached statistical significance in Japanese. The analysis of the AGT-GT repeat revealed marked linkage disequilibriums between each of the diallelic polymorphisms and some (GT)n alleles, with similar patterns in the two populations. The strong disequilibrium between M235 and (GT)16 explained the increased frequency of that particular allele in French controls compared with hypertensives (.42 vs. .36, P < .01). The haplotype combining the M235T and G-6A polymorphisms appears as the ancestral allele of the human AGT gene and as the one associated with hypertension. PMID:9199566

  13. Water quality associated public health risk in Bo, Sierra Leone.

    PubMed

    Jimmy, David H; Sundufu, Abu J; Malanoski, Anthony P; Jacobsen, Kathryn H; Ansumana, Rashid; Leski, Tomasz A; Bangura, Umaru; Bockarie, Alfred S; Tejan, Edries; Lin, Baochuan; Stenger, David A

    2013-01-01

    Human health depends on reliable access to safe drinking water, but in many developing countries only a limited number of wells and boreholes are available. Many of these water resources are contaminated with biological or chemical pollutants. The goal of this study was to examine water access and quality in urban Bo, Sierra Leone. A health census and community mapping project in one neighborhood in Bo identified the 36 water sources used by the community. A water sample was taken from each water source and tested for a variety of microbiological and physicochemical substances. Only 38.9% of the water sources met World Health Organization (WHO) microbial safety requirements based on fecal coliform levels. Physiochemical analysis indicated that the majority (91.7%) of the water sources met the requirements set by the WHO. In combination, 25% of these water resources met safe drinking water criteria. No variables associated with wells were statistically significant predictors of contamination. This study indicated that fecal contamination is the greatest health risk associated with drinking water. There is a need to raise hygiene awareness and implement inexpensive methods to reduce fecal contamination and improve drinking water safety in Bo, Sierra Leone. PMID:22350346

  14. An age-dependent model to analyse the evolutionary stability of bacterial quorum sensing.

    PubMed

    Mund, A; Kuttler, C; Pérez-Velázquez, J; Hense, B A

    2016-09-21

    Bacterial communication is enabled through the collective release and sensing of signalling molecules in a process called quorum sensing. Cooperative processes can easily be destabilized by the appearance of cheaters, who contribute little or nothing at all to the production of common goods. This especially applies for planktonic cultures. In this study, we analyse the dynamics of bacterial quorum sensing and its evolutionary stability under two levels of cooperation, namely signal and enzyme production. The model accounts for mutation rates and switches between planktonic and biofilm state of growth. We present a mathematical approach to model these dynamics using age-dependent colony models. We explore the conditions under which cooperation is stable and find that spatial structuring can lead to long-term scenarios such as coexistence or bistability, depending on the non-linear combination of different parameters like death rates and production costs. PMID:26796220

  15. Age-dependent T cell tolerance and autoimmunity to myelin basic protein.

    PubMed

    Huseby, E S; Sather, B; Huseby, P G; Goverman, J

    2001-04-01

    Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, is induced by activating a subset of myelin basic protein (MBP)-specific T cells that have escaped tolerance induction. Here, we define the tolerance mechanisms that eliminate the majority of MBP-specific T cells from the periphery. We show that MBP-specific T cells undergo central tolerance mediated by bone marrow-derived antigen-presenting cells presenting exogenously derived MBP epitopes. The efficiency of tolerance is age dependent, reflecting the developmentally regulated expression of MBP. Dependence of tolerance on the amount of MBP expressed in vivo results in an age window of susceptibility to EAE in mice that peaks during puberty. These results suggest that factors regulating expression of self-antigens in vivo can influence susceptibility to autoimmunity. PMID:11336692

  16. Age-dependent changes in cat masseter nerve: an electrophysiological and morphological study.

    PubMed

    Chase, M H; Engelhardt, J K; Adinolfi, A M; Chirwa, S S

    1992-07-24

    The present study was undertaken to determine the manner in which aging affects the function and structure of the masseter nerve in old cats. Electrophysiological data demonstrated a significant decrease in the conduction velocity of the action potential in old cats compared with that observed in adult cats. Light microscopic analyses revealed an age-dependent decrease in axon diameter. Electron microscopic observations of the masseter nerve in the aged cats revealed a disruption of the myelin sheaths and a pronounced increase in collagen fibers in the endoneurium and perineurium. These morphological changes are discussed and then related to the decrease in conduction velocity which was observed in the electrophysiological portion of this study. PMID:1521161

  17. Age-dependent accumulation of (137)Cs by pike Esox lucius in the Yenisei River.

    PubMed

    Zotina, T A; Trofimova, E A; Dementyev, D V; Bolsunovsky, A Ya

    2016-05-01

    Age-dependent accumulation of (137)Cs in the muscles and bodies of the pike Esox lucius (aged two to seven years) inhabiting a section of the Yenisei River polluted with artificial radionuclides has been studied. The content of (137)Cs in muscles varied from 0.5 to 7.0 Bq/kg of fresh weight. The maximum content of the radionuclide has been found in juveniles. The content of (137)Cs in pike muscles and body decreased considerably with age. The high content of (137)Cs in the muscles of juveniles is probably a consequence of their higher intensity of feeding as compared to older individuals, which is due to the intense growth of juveniles. PMID:27411826

  18. Age-dependent changes in T cell homeostasis and SIV load in sooty mangabeys.

    PubMed

    Chakrabarti, L A; Lewin, S R; Zhang, L; Gettie, A; Luckay, A; Martin, L N; Skulsky, E; Ho, D D; Cheng-Mayer, C; Marx, P A

    2000-08-01

    Sooty mangabeys (Cercocebus atys) showed age-dependent changes in T cell regeneration. Younger animals had a high percentage of CD4+ CD45RA + T cells and a high concentration of T cell receptor excisional circles (TRECs) in peripheral blood, which indicated active thymopoiesis. In contrast, older animals had an increased T cell turnover, which suggested that most T cell production occurred in the periphery. In addition, the number of peripheral CD4+ T cells naturally decreased with age. Non-pathogenic SIVsm infection did not significantly change the T cell proliferation rate or the TREC concentration, though it did cause a moderate loss of peripheral CD4 + T cells. The viral load correlated negatively with age, which could be accounted for by the reduced availability of CD4 + target cells in older mangabeys. Thus, the number of susceptible target cells may be a limiting factor in natural SIV infection. PMID:11085578

  19. Age-Dependent Susceptibility of Chromosome Cohesion to Premature Separase Activation in Mouse Oocytes1

    PubMed Central

    Chiang, Teresa; Schultz, Richard M.; Lampson, Michael A.

    2011-01-01

    ABSTRACT A hypothesis to explain the maternal age-dependent increase in formation of aneuploid eggs is deterioration of chromosome cohesion. Although several lines of evidence are consistent with this hypothesis, whether cohesion is actually reduced in naturally aged oocytes has not been directly tested by any experimental perturbation. To directly target cohesion, we increased the activity of separase, the protease that cleaves the meiotic cohesin REC8, in oocytes. We show that cohesion is more susceptible to premature separase activation in old oocytes than in young oocytes, demonstrating that cohesion is significantly reduced. Furthermore, cohesion is protected by two independent mechanisms that inhibit separase, securin and an inhibitory phosphorylation of separase by CDK1; both mechanisms must be disrupted to prematurely activate separase. With the continual loss of cohesins from chromosomes that occurs throughout the natural reproductive lifespan, tight regulation of separase in oocytes may be particularly important to maintain cohesion and prevent aneuploidy. PMID:21865557

  20. Cadmium affects the episodic luteinizing hormone secretion in male rats: possible age-dependent effects.

    PubMed

    Lafuente, A; Márquez, N; Piquero, S; Esquifino, A I

    1999-01-11

    Cadmium affects luteinizing hormone (LH) secretion through unknown mechanisms. The present study was undertaken to assess whether chronic exposure to low concentrations of cadmium may affect the episodic secretion of LH and if these effects are age-dependent. Male rats were given cadmium at a dose of 50 ppm in the drinking water, from day 30 to 60 or from day 60 to 90 of life. Age-matched rats with access to cadmium-free water were used as controls. At the end of the treatment, blood samples were collected every 7 min for 3 h, from 10:30 to 13.30 in conscious, freely moving rats. In control animals, mean serum LH levels and pulse duration increased with age (P < or = 0.001), and pulse frequency and the relative amplitude of LH pulses decreased (P < or = 0.001). Cadmium administration, from day 30 to 60 of life, decreased the pulse frequency and mean half-life of the hormone (P < or = 0.05, P < or = 0.01, respectively). However, no changes in any other parameters studied were observed as compared to the control group. When cadmium was administered from day 60 to 90, mean serum LH levels and the duration of LH pulses decreased (P < or = 0.05), whereas the pulse frequency increased (P < or = 0.05). The absolute and relative amplitude of the LH peaks and the mean half-life of the hormone were not changed after cadmium administration from day 60 to 90. These results indicate that low doses of cadmium change the pulsatile secretion of LH in male rats and that the effect of cadmium on episodic LH release was age-dependent. PMID:10048746

  1. Age-Dependent Effects of Haptoglobin Deletion in Neurobehavioral and Anatomical Outcomes Following Traumatic Brain Injury

    PubMed Central

    Glushakov, Alexander V.; Arias, Rodrigo A.; Tolosano, Emanuela; Doré, Sylvain

    2016-01-01

    Cerebral hemorrhages are common features of traumatic brain injury (TBI) and their presence is associated with chronic disabilities. Recent clinical and experimental evidence suggests that haptoglobin (Hp), an endogenous hemoglobin-binding protein most abundant in blood plasma, is involved in the intrinsic molecular defensive mechanism, though its role in TBI is poorly understood. The aim of this study was to investigate the effects of Hp deletion on the anatomical and behavioral outcomes in the controlled cortical impact model using wildtype (WT) C57BL/6 mice and genetically modified mice lacking the Hp gene (Hp−∕−) in two age cohorts [2–4 mo-old (young adult) and 7–8 mo-old (older adult)]. The data obtained suggest age-dependent significant effects on behavioral and anatomical TBI outcomes and recovery from injury. Moreover, in the adult cohort, neurological deficits in Hp−∕− mice at 24 h were significantly improved compared to WT, whereas there were no significant differences in brain pathology between these genotypes. In contrast, in the older adult cohort, Hp−∕− mice had significantly larger lesion volumes compared to WT, but neurological deficits were not significantly different. Immunohistochemistry for ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) revealed significant differences in microglial and astrocytic reactivity between Hp−∕− and WT in selected brain regions of the adult but not the older adult-aged cohort. In conclusion, the data obtained in the study provide clarification on the age-dependent aspects of the intrinsic defensive mechanisms involving Hp that might be involved in complex pathways differentially affecting acute brain trauma outcomes. PMID:27486583

  2. Age-dependent speciation can explain the shape of empirical phylogenies.

    PubMed

    Hagen, Oskar; Hartmann, Klaas; Steel, Mike; Stadler, Tanja

    2015-05-01

    Tens of thousands of phylogenetic trees, describing the evolutionary relationships between hundreds of thousands of taxa, are readily obtainable from various databases. From such trees, inferences can be made about the underlying macroevolutionary processes, yet remarkably these processes are still poorly understood. Simple and widely used evolutionary null models are problematic: Empirical trees show very different imbalance between the sizes of the daughter clades of ancestral taxa compared to what models predict. Obtaining a simple evolutionary model that is both biologically plausible and produces the imbalance seen in empirical trees is a challenging problem, to which none of the existing models provide a satisfying answer. Here we propose a simple, biologically plausible macroevolutionary model in which the rate of speciation decreases with species age, whereas extinction rates can vary quite generally. We show that this model provides a remarkable fit to the thousands of trees stored in the online database TreeBase. The biological motivation for the identified age-dependent speciation process may be that recently evolved taxa often colonize new regions or niches and may initially experience little competition. These new taxa are thus more likely to give rise to further new taxa than a taxon that has remained largely unchanged and is, therefore, well adapted to its niche. We show that age-dependent speciation may also be the result of different within-species populations following the same laws of lineage splitting to produce new species. As the fit of our model to the tree database shows, this simple biological motivation provides an explanation for a long standing problem in macroevolution. PMID:25575504

  3. Estrogen Effects on Vascular Inflammation are Age-Dependent: Role of Estrogen Receptors

    PubMed Central

    Kapadia, Akash; Chen, Yiu-Fai; Szalai, Alexander J.; Oparil, Suzanne; Hage, Fadi G.

    2014-01-01

    Objective 17β-Estradiol (E2) offers cardiovascular protection in young female animals and postmenopausal women. In contrast, randomized trials of menopausal hormones carried out in older women have shown harm or no cardiovascular benefit. We hypothesize that E2 effects on vascular inflammation are age-dependent. Approach and Results Young (10-wk) and aged (52-wk) female C57BL/6 mice were used as source for primary cultures of bone marrow-derived macrophages (BMMs) and vascular smooth muscle cells (VSMCs). E2 pre-treatment of cells derived from young mice attenuated C-reactive protein (CRP)-induced expression of inflammatory mediators. In contrast, E2 pre-treatment of cells from aged mice did not alter (BMMs) or paradoxically exaggerated (VSMCs) inflammatory mediator response to CRP. Using E2 receptor (ER)-knockout mice, we demonstrated that E2 regulates inflammatory response to CRP in BMMs via ERα and in VSMCs via ERβ. BMMs derived from aged (vs. young) mice expressed significantly less ERα mRNA and protein. A selective ligand of the novel ER GPR30 reproduced the E2 effects in BMMs and VSMCs. Unlike in young mice, E2 did not reduce neointima formation in ligated carotid arteries of aged CRP transgenic mice. Conclusions E2 attenuates inflammatory response to CRP in BMMs and VSMCs derived from young but not aged mice and reduces neointima formation in injured carotid arteries of young but not aged CRP transgenic mice. ERα expression in BMMs is greatly diminished with aging. These data suggest that vasoprotective effects of E2 are age-dependent and may explain the vasotoxic effects of E2 seen in clinical trials of postmenopausal women. PMID:24876352

  4. Pharmacological and genetic reversal of age dependent cognitive deficits due to decreased presenilin function

    PubMed Central

    McBride, Sean M. J.; Choi, Catherine H.; Schoenfeld, Brian P.; Bell, Aaron J.; Liebelt, David A.; Ferreiro, David; Choi, Richard J.; Hinchey, Paul; Kollaros, Maria; Terlizzi, Allison M.; Ferrick, Neal J.; Koenigsberg, Eric; Rudominer, Rebecca L.; Sumida, Ai; Chiorean, Stephanie; Siwicki, Kathleen K.; Nguyen, Hanh T.; Fortini, Mark E.; McDonald, Thomas V.; Jongens, Thomas A.

    2010-01-01

    Alzheimer's disease is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are due to mutations in a single copy of the Presenilin (PS) and Amyloid Precursor Protein (APP) genes. The dominant inheritance pattern of FAD indicates that it may be due to gain or change of function mutations. Studies of FAD-linked forms of presenilin in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of DmGluRA, the inositol trisphosphate receptor (InsP3R) or IPPase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP3R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced. PMID:20631179

  5. The probiotic mixture IRT5 ameliorates age-dependent colitis in rats.

    PubMed

    Jeong, Jin-Ju; Woo, Jae-Yeon; Ahn, Young-Tae; Shim, Jae-Hun; Huh, Chul-Sung; Im, Sin-Heog; Han, Myung Joo; Kim, Dong-Hyun

    2015-06-01

    To investigate the anti-inflammatory effect of probiotics, we orally administered IRT5 (1×10(9)CFU/rat) for 8 weeks to aged (16 months-old) Fischer 344 rats, and measured parameters of colitis. The expression levels of the inflammatory markers' inducible NO synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were higher in the colons of normal aged rats (18 months-old) than in the colons of normal young rats (6 months-old). Treatment with IRT5 suppressed the age-associated increased expression of iNOS, COX2, TNF-α, and IL-1β, and activation of NF-κB and mitogen-activated protein kinases. In a similar manner, the expression of tight junction proteins in the colon of normal aged rats was suppressed more potently than in normal young rats, and treatment of aged rats with IRT5 decreased the age-dependent suppression of tight junction proteins ZO-1, occludin, and claudin-1. Treatment with IRT5 suppressed age-associated increases in expressions of senescence markers p16 and p53 in the colon of aged rats, but increased age-suppressed expression of SIRT1. However, treatment with IRT5 inhibited age-associated increased myeloperoxidase activity in the colon. In addition, treatment with IRT5 lowered the levels of LPS in intestinal fluid and blood of aged rats, as well as the reduced concentrations of reactive oxygen species, malondialdehyde, and C-reactive protein in the blood. These findings suggest that IRT5 treatment may suppress age-dependent colitis by inhibiting gut microbiota LPS production. PMID:25907245

  6. Is the metabolism of 25-hydroxyvitamin D3 age-dependent in dairy cows?

    PubMed

    Wilkens, Mirja R; Cohrs, Imke; Lifschitz, Adrian L; Fraser, David R; Olszewski, Katharina; Schröder, Bernd; Breves, Gerhard

    2013-07-01

    It has recently been demonstrated that prepartum administered 25-hydroxyvitamin D3 (25-OHD3) is a promising candidate to assist the maintenance of peripartal calcium homeostasis in dairy cows. Since the incidence of peripartal hypocalcemia and the reported beneficial effects of the treatment are both associated with the lactation number, we investigated pharmacokinetic aspects of 25-OHD3 related to the age of dairy cows. The daily oral administration of 3mg 25-OHD3 in rapeseed oil as well as a treatment with 4 and 6mg included in the feed during the last eight to ten days of gestation resulted in linear dosage- and age-dependent increases in plasma 25-OHD3. After parturition the administration was stopped and blood samples were taken to calculate the plasma half-life. Irrespective of the supplemented dosage, cows starting the 2nd lactation showed a significantly longer plasma half-life of 25-OHD3 than cows starting the 3rd or higher lactation. Age-dependent differences in the increase of plasma 25-OHD3 could already be found before parturition when calcium homeostasis was not yet significantly challenged. Additionally, no correlations between plasma half-life of 25-OHD3 and 1,25-dihydroxyvitamin D3, PTH or the bone resorption marker CrossLaps were observed after parturition. Thus we conclude that the influence of the lactation number on the pharmacokinetics of 25-OHD3 is related directly to the age of the cows. This article is part of a Special Issue entitled 'Vitamin D Workshop'. PMID:23220546

  7. Assigning linkage haplotypes from parent and progeny genotypes

    SciTech Connect

    Nejati-Javaremi, A.; Smith, C.

    1996-04-01

    Given the genotypes of parents and progeny, their haplotypes over several or many linked loci can be easily assigned by listing the allele type at each locus along the haplotype known to be from each parent. Only a small number (5-10) of progeny per family is usually needed to assign the parental and progeny haplotypes. Any gaps left in the haplotypes may be filled in from the assigned haplotypes of relatives. The process is facilitated by having multiple alleles at the loci and by using more linked loci in the haplotype and with more progeny from the mating. Crossover haplotypes in the progeny can be identified by their being unique or uncommon, and the crossover point can often be detected if the locus linkage map order is known. The haplotyping method applies to outbreeding populations in plants, animals, and man, as well as to traditional experimental crosses of inbred lines. The method also applies to half-sib families, whether the genotype of the mates are known or unknown. The haplotyping procedure is already used in linkage analysis but does not seem to have been published. It should be useful in teaching and in genetic applications of haplotypes. 15 refs., 5 tabs.

  8. An improved preprocessing algorithm for haplotype inference by pure parsimony.

    PubMed

    Choi, Mun-Ho; Kang, Seung-Ho; Lim, Hyeong-Seok

    2014-08-01

    The identification of haplotypes, which encode SNPs in a single chromosome, makes it possible to perform a haplotype-based association test with disease. Given a set of genotypes from a population, the process of recovering the haplotypes, which explain the genotypes, is called haplotype inference (HI). We propose an improved preprocessing method for solving the haplotype inference by pure parsimony (HIPP), which excludes a large amount of redundant haplotypes by detecting some groups of haplotypes that are dispensable for optimal solutions. The method uses only inclusion relations between groups of haplotypes but dramatically reduces the number of candidate haplotypes; therefore, it causes the computational time and memory reduction of real HIPP solvers. The proposed method can be easily coupled with a wide range of optimization methods which consider a set of candidate haplotypes explicitly. For the simulated and well-known benchmark datasets, the experimental results show that our method coupled with a classical exact HIPP solver run much faster than the state-of-the-art solver and can solve a large number of instances that were so far unaffordable in a reasonable time. PMID:25152045

  9. Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina.

    PubMed

    Henning, Yoshiyuki; Szafranski, Karol

    2016-01-01

    The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4) are crucial for retinal development and function, and increasing evidence points at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise regulation of retinal TH supply is required for proper retinal function, but knowledge on these mechanisms is still fragmentary. Several transmembrane transporters have been described as key regulators of TH availability in target tissues of which the monocarboxylate transporter 8 (MCT8), a high affinity transporter for T4 and T3, plays an essential role in the central nervous system. Moreover, in the embryonic chicken retina, MCT8 is highly expressed, but the postnatal availability of MCT8 in the mammalian retina was not reported to date. In the present study, spatiotemporal retinal MCT8 availability was examined in mice of different age. For this purpose, we quantified expression levels of Mct8 via Real-Time Reverse-Transcriptase PCR in mouse eyecups (C57BL/6) of juvenile and adult age groups. Additionally, age-dependent MCT8 protein levels were quantified via Western blotting and localized via immunofluorescence confocal microscopy. While no difference in Mct8 expression levels could be detected between age groups, MCT8 protein levels in juvenile animals were about two times higher than in adult animals based on Western blot analyses. Immunohistochemical analyses showed that MCT8 immunoreactivity in the eyecup was restricted to the retina and the retinal pigment epithelium. In juvenile mice, MCT8 was broadly observed along the apical membrane of the retinal pigment epithelium, tightly surrounding photoreceptor outer segments. Distinct immunopositive staining was also detected in the inner nuclear layer and the ganglion cell layer. However, in adult specimens, immunoreactivity visibly declined in all layers, which was in line with Western blot analyses. Since MCT8 was abundantly present in juvenile and about twofold lower in

  10. Age-dependent chloride channel expression in skeletal muscle fibres of normal and HSALR myotonic mice

    PubMed Central

    DiFranco, Marino; Yu, Carl; Quiñonez, Marbella; Vergara, Julio L

    2013-01-01

    We combine electrophysiological and optical techniques to investigate the role that the expression of chloride channels (ClC-1) plays on the age-dependent electrical properties of mammalian muscle fibres. To this end, we comparatively evaluate the magnitude and voltage dependence of chloride currents (ICl), as well as the resting resistance, in fibres isolated from control and human skeletal actin (HSA)LR mice (a model of myotonic dystrophy) of various ages. In control mice, the maximal peak chloride current ([peak-ICl]max) increases from −583 ± 126 to −956 ± 260 μA cm−2 (mean ± SD) between 3 and 6 weeks old. Instead, in 3-week-old HSALR mice, ICl are significantly smaller (−153 ± 33 μA cm−2) than in control mice, but after a long period of ∼14 weeks they reach statistically comparable values. Thus, the severe ClC-1 channelopathy in young HSALR animals is slowly reversed with aging. Frequency histograms of the maximal chloride conductance (gCl,max) in fibres of young HSALR animals are narrow and centred in low values; alternatively, those from older animals show broad distributions, centred at larger gCl,max values, compatible with mosaic expressions of ClC-1 channels. In fibres of both animal strains, optical data confirm the age-dependent increase in gCl, and additionally suggest that ClC-1 channels are evenly distributed between the sarcolemma and transverse tubular system membranes. Although gCl is significantly depressed in fibres of young HSALR mice, the resting membrane resistance (Rm) at −90 mV is only slightly larger than in control mice due to upregulation of a Rb-sensitive resting conductance (gK,IR). In adult animals, differences in Rm are negligible between fibres of both strains, and the contributions of gCl and gK,IR are less altered in HSALR animals. We surmise that while hyperexcitability in young HSALR mice can be readily explained on the basis of reduced gCl, myotonia in adult HSALR animals may be explained on the basis of a

  11. Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina

    PubMed Central

    Henning, Yoshiyuki; Szafranski, Karol

    2016-01-01

    The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4) are crucial for retinal development and function, and increasing evidence points at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise regulation of retinal TH supply is required for proper retinal function, but knowledge on these mechanisms is still fragmentary. Several transmembrane transporters have been described as key regulators of TH availability in target tissues of which the monocarboxylate transporter 8 (MCT8), a high affinity transporter for T4 and T3, plays an essential role in the central nervous system. Moreover, in the embryonic chicken retina, MCT8 is highly expressed, but the postnatal availability of MCT8 in the mammalian retina was not reported to date. In the present study, spatiotemporal retinal MCT8 availability was examined in mice of different age. For this purpose, we quantified expression levels of Mct8 via Real-Time Reverse-Transcriptase PCR in mouse eyecups (C57BL/6) of juvenile and adult age groups. Additionally, age-dependent MCT8 protein levels were quantified via Western blotting and localized via immunofluorescence confocal microscopy. While no difference in Mct8 expression levels could be detected between age groups, MCT8 protein levels in juvenile animals were about two times higher than in adult animals based on Western blot analyses. Immunohistochemical analyses showed that MCT8 immunoreactivity in the eyecup was restricted to the retina and the retinal pigment epithelium. In juvenile mice, MCT8 was broadly observed along the apical membrane of the retinal pigment epithelium, tightly surrounding photoreceptor outer segments. Distinct immunopositive staining was also detected in the inner nuclear layer and the ganglion cell layer. However, in adult specimens, immunoreactivity visibly declined in all layers, which was in line with Western blot analyses. Since MCT8 was abundantly present in juvenile and about twofold lower in

  12. First record of Tenuipalpus uvae De Leon, 1962 (Acari: Tenuipalpidae) in Brazil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This is the first record of Tenuipalpus uvae De Leon (Tenuipalpidae) in Brazil. Specimens were collected from Spondias mombin L. (Anacardiaceae) in the states of Amapa (Northern Brazil) and Pernambuco (northeast)....

  13. Notes from The Field: Ebola Virus Disease Cluster - Northern Sierra Leone, January 2016.

    PubMed

    Alpren, Charles; Sloan, Michelle; Boegler, Karen A; Martin, Daniel W; Ervin, Elizabeth; Washburn, Faith; Rickert, Regan; Singh, Tushar; Redd, John T

    2016-01-01

    On January 14, 2016, the Sierra Leone Ministry of Health and Sanitation was notified that a buccal swab collected on January 12 from a deceased female aged 22 years (patient A) in Tonkolili District had tested positive for Ebola virus by reverse transcription-polymerase chain reaction (RT-PCR). The most recent case of Ebola virus disease (Ebola) in Sierra Leone had been reported 4 months earlier on September 13, 2015 (1), and the World Health Organization had declared the end of Ebola virus transmission in Sierra Leone on November 7, 2015 (2). The Government of Sierra Leone launched a response to prevent further transmission of Ebola virus by identifying contacts of the decedent and monitoring them for Ebola signs and symptoms, ensuring timely treatment for anyone with Ebola, and conducting an epidemiologic investigation to identify the source of infection. PMID:27388584

  14. Ebola response in Sierra Leone: The impact on children.

    PubMed

    Fitzgerald, Felicity; Awonuga, Waheed; Shah, Tejshri; Youkee, Daniel

    2016-07-01

    The West African Ebola virus disease (EVD) outbreak is the largest ever seen, with over 28,000 cases and 11,300 deaths since early 2014. The magnitude of the outbreak has tested fragile governmental health systems and non-governmental organizations (NGOs) to their limit. Here we discuss the outbreak in the Western Area of Sierra Leone, the shape of the local response and the impact the response had on caring for children suspected of having contracted EVD. Challenges encountered in providing clinical care to children whilst working in the "Red Zone" where risk of EVD is considered to be highest, wearing full personal protective equipment are detailed. Suggestions and recommendations both for further research and for operational improvement in the future are made, with particular reference as to how a response could be more child-focused. PMID:27177732

  15. Haplotype kinship for three populations of the Goettingen minipig

    PubMed Central

    Flury, Christine; Weigend, Steffen; Ding, Xiangdong; Täubert, Helge; Simianer, Henner

    2007-01-01

    To overcome limitations of diversity measures applied to livestock breeds marker based estimations of kinship within and between populations were proposed. This concept was extended from the single locus consideration to chromosomal segments of a given length in Morgan. Algorithms for the derivation of haplotype kinship were suggested and the behaviour of marker based haplotype kinship was investigated theoretically. In the present study the results of the first practical application of this concept are presented. Full sib pairs of three sub-populations of the Goettingen minipig were genotyped for six chromosome segments. After haplotype reconstruction the haplotypes were compared and mean haplotype kinships were estimated within and between populations. Based on haplotype kinships a distance measure is proposed which is approximatively linear with the number of generations since fission. The haplotype kinship distances, the respective standard errors and the pedigree-based expected values are presented and are shown to reflect the true population history better than distances based on single-locus kinships. However the marker estimated haplotype kinship reveals variable among segments. This leads to high standard errors of the respective distances. Possible reasons for this phenomenon are discussed and a pedigree-based approach to correct for identical haplotypes which are not identical by descent is proposed. PMID:17306199

  16. Genomic evolution in domestic cattle: ancestral haplotypes and healthy beef.

    PubMed

    Williamson, Joseph F; Steele, Edward J; Lester, Susan; Kalai, Oscar; Millman, John A; Wolrige, Lindsay; Bayard, Dominic; McLure, Craig; Dawkins, Roger L

    2011-05-01

    We have identified numerous Ancestral Haplotypes encoding a 14-Mb region of Bota C19. Three are frequent in Simmental, Angus and Wagyu and have been conserved since common progenitor populations. Others are more relevant to the differences between these 3 breeds including fat content and distribution in muscle. SREBF1 and Growth Hormone, which have been implicated in the production of healthy beef, are included within these haplotypes. However, we conclude that alleles at these 2 loci are less important than other sequences within the haplotypes. Identification of breeds and hybrids is improved by using haplotypes rather than individual alleles. PMID:21338665

  17. Bayesian Modeling of Haplotype Effects in Multiparent Populations

    PubMed Central

    Zhang, Zhaojun; Wang, Wei; Valdar, William

    2014-01-01

    A general Bayesian model, Diploffect, is described for estimating the effects of founder haplotypes at quantitative trait loci (QTL) detected in multiparental genetic populations; such populations include the Collaborative Cross (CC), Heterogeneous Socks (HS), and many others for which local genetic variation is well described by an underlying, usually probabilistically inferred, haplotype mosaic. Our aim is to provide a framework for coherent estimation of haplotype and diplotype (haplotype pair) effects that takes into account the following: uncertainty in haplotype composition for each individual; uncertainty arising from small sample sizes and infrequently observed haplotype combinations; possible effects of dominance (for noninbred subjects); genetic background; and that provides a means to incorporate data that may be incomplete or has a hierarchical structure. Using the results of a probabilistic haplotype reconstruction as prior information, we obtain posterior distributions at the QTL for both haplotype effects and haplotype composition. Two alternative computational approaches are supplied: a Markov chain Monte Carlo sampler and a procedure based on importance sampling of integrated nested Laplace approximations. Using simulations of QTL in the incipient CC (pre-CC) and Northport HS populations, we compare the accuracy of Diploffect, approximations to it, and more commonly used approaches based on Haley–Knott regression, describing trade-offs between these methods. We also estimate effects for three QTL previously identified in those populations, obtaining posterior intervals that describe how the phenotype might be affected by diplotype substitutions at the modeled locus. PMID:25236455

  18. When does maternal age-dependent trisomy 21 arise relative to meiosis?

    SciTech Connect

    Chang-Jiang Zheng; Byers, B.

    1996-07-01

    Polymorphic DNA markers have recently been used to estimate the fraction of trisomy 21 (Down syndrome) cases that may be attributable to postzygotic nondisjunction - indicative of a loss in the fidelity of the first few cell divisions after fertilization. In these studies, a postzygotic nondisjunction is defined as a case in which two chromosomes of the trisomic set are homozygous for all informative markers (i.e., for those markers that were heterozygous in their parent of origin). These studies estimate that the postzygotic mutation mechanism accounts for 4.5% (11/238) and 3.5% (9/255) of their cases, respectively, but their estimates may actually be conservative, since all noninformative haplotypes (frequency not reported) are arbitrarily attributed to meiosis II-type nondisjunction. Nevertheless, even the conservative estimates would, if confirmed, constitute a new and nonnegligible source of chromosomal segregation errors leading to trisomy. These studies` conclusions are supported by the observation that the 20 reported {open_quotes}postzygotic{close_quotes} cases (5 paternal and 15 maternal) appear to be less dependent on maternal age (mean maternal age 28.4 years) than maternal meiosis I-type failures (mean maternal age 31.2 years). However, given the limited sample size involved, one should be cautious in positing the absence of a maternal age effect. 5 refs., 1 fig.

  19. Knowledge of breast cancer in women in Sierra Leone.

    PubMed

    Shepherd, J H E E; McInerney, P A

    2006-08-01

    Breast cancer has been described as one of the life-threatening diseases affecting women and is a major problem in women's health issues. The unrecorded number of cases of breast lumps and breast cancer observed in women in Sierra Leone prompted the researcher to organize a "Breast Week" during which 1,200 women were educated on breast cancer and the importance of breast health. This research is a follow up of the "Breast Week" which was organized in Freetown, Sierra Leone The specific objective of this study was to assess whether the knowledge and teachings given to the women who participated in this project was fully understood. A sample size of 120 women (10%) who participated in the "Breast Week" was obtained through systematic sampling. A quantitative approach was adopted and a structured interview schedule guided the data collection process. The data were processed through use of SPSS and Microsoft Excel. Texts from open ended questions were categorized and frequency counts were applied to the data. It was found that the majority (96.6%) of the women had some knowledge of breast cancer. They linked breast cancer to the signs and symptoms associated with it and were able to describe the disease as one that kills women if not promptly detected and/or treated appropriately. Findings indicate that the majority of the women are aware of the dangers of the disease and had knowledge of someone who had died of breast cancer (59.2%). An assessment of the effectiveness of knowledge on breast cancer showed that these women could identify breast cancer as a disease that affects women and may cause death if not detected on time. PMID:17131611

  20. Aetiology of uveitis in Sierra Leone, west Africa.

    PubMed Central

    Ronday, M J; Stilma, J S; Barbe, R F; McElroy, W J; Luyendijk, L; Kolk, A H; Bakker, M; Kijlstra, A; Rothova, A

    1996-01-01

    BACKGROUND: In 1992, non-onchocercal uveitis caused 9% of blindness, 8% of visual impairment, and 11% of uniocular blindness among patients visiting an eye hospital in Sierra Leone, west Africa. The aim of this study was to determine the aetiology of uveitis in this population. METHODS: General and ophthalmic examination complemented by serum and aqueous humour analyses for various infectious agents was performed for 93 uveitis patients and compared with serum (n = 100) and aqueous humour (n = 9) analysis of endemic controls. RESULTS: At the initial examination, 45 patients (48%) proved to be severely visually handicapped. After clinical and laboratory analyses, an aetiological diagnosis was established for 49 patients (52%). Toxoplasma gondii was the most important cause of uveitis (40/93; 43%). Anti-toxoplasma IgM antibodies were detected in serum samples of seven of 93 patients (8%) compared with one of 100 controls (1%, p < 0.05). At least six patients (15%) with ocular toxoplasmosis had acquired the disease postnatally. Antibodies against Treponema pallidum were detected in 18 of 92 patients (20%) and in 21 controls (21%). Other causes of uveitis were varicella zoster virus (one patient), herpes simplex virus (two patients), and HLA-B27 positive acute anterior uveitis with ankylosing spondylitis (one patient), while one patient had presumed HTLV-I uveitis. CONCLUSIONS: In a hospital population in Sierra Leone, west Africa, uveitis was associated with severe visual handicap and infectious diseases. Toxoplasmosis proved to be the most important cause of the uveitis. Although the distribution of congenital versus acquired toxoplasmosis in this population could not be determined, the results indicate an important role of postnatally acquired disease. The results further suggested minor roles for HIV, tuberculosis, toxocariasis, and sarcoidosis as causes of uveitis in this population. PMID:8976721

  1. A comparison of egocentric and allocentric age-dependent spatial learning in the beagle dog.

    PubMed

    Christie, Lori-Ann; Studzinski, Christa M; Araujo, Joseph A; Leung, Cleo S K; Ikeda-Douglas, Candace J; Head, Elizabeth; Cotman, Carl W; Milgram, Norton W

    2005-03-01

    Spatial discriminations can be performed using either egocentric information based on body position or allocentric information based on the position of landmarks in the environment. Beagle dogs ranging from 2 to 16 years of age were tested for their ability to learn a novel egocentric spatial discrimination task that used two identical blocks paired in three possible spatial positions (i.e. left, center and right). Dogs were rewarded for responding to an object furthest to either their left or right side. Therefore, when the center location was used, it was correct on half of the trials and incorrect on the other half. Upon successful acquisition of the task, the reward contingencies were reversed, and the dogs were rewarded for responding to the opposite side. A subset of dogs was also tested on an allocentric spatial discrimination task, landmark discrimination. Egocentric spatial reversal learning and allocentric discrimination learning both showed a significant age-dependent decline, while initial egocentric learning appeared to be age-insensitive. Intra-subject correlation analyses revealed a significant relationship between egocentric reversal learning and allocentric learning. However, the correlation only accounted for a small proportion of the variance, suggesting that although there might be some common mechanism underlying acquisition of the two tasks, additional unique neural substrates were involved depending on whether allocentric or egocentric spatial information processing was required. PMID:15795044

  2. Age-dependent responses to chemosensory cues mediating kin recognition in dogs (Canis familiaris)

    PubMed

    Mekosh-Rosenbaum, V; Carr, W J; Goodwin, J L; Thomas, P L; D'Ver, A; Wysocki, C J

    1994-03-01

    During individually administered 5-min tests conducted in a neutral cage, four age groups (n = 10 males and 10 females per group) of purebred beagles reacted to bedding from their home cage vs. bedding from another litter of the same age. The 20-24-day-old males and females preferred (p < 0.05) home cage bedding over strange cage bedding. Those aged 31-36 days or 66-72 days showed no reliable preference for either type of bedding. Among pups aged 52-56 days, the males preferred (p < 0.05) strange cage bedding, but the females showed no reliable preference. Chemosensory cues are sufficient as mediators of kin recognition in beagles, but their reactions to such cues vary with age-dependent factors, some stemming from changes in the strength of the mother-litter bond. The dogs providing the two types of bedding lived in the same room and on the same diet. Therefore, kin recognition could not have been mediated by different chemosensory cues produced by variations in these environmental factors. PMID:8190767

  3. Cognitive experience and its effect on age-dependent cognitive decline in beagle dogs.

    PubMed

    Milgram, Norton W

    2003-11-01

    Test-sophisticated beagle dogs show marked age sensitivity in a size discrimination learning task, with old and senior dogs performing significantly more poorly than young dogs. By contrast, age differences in learning were not seen in dogs naive with respect to neuropsychological test experience. These results indicate that old animals benefit less from prior cognitive experience than young animals, which is an example of an age-dependent loss in plasticity. This finding also suggests that behaviorally experienced animals are a more useful model of human cognitive aging than behaviorally naïve animals. We also looked at the effect of a program of behavioral enrichment in aged dogs. One year of enrichment did not lead to significant differences, but after 2 years the behaviorally enriched group performed significantly better than the control group. The effect after 2 years indicates that a prolonged program of cognitive enrichment can serve as an effective intervention in aged dogs. These findings demonstrate that cognitive abilities in aged animals can be modified by providing behavioral experience, indicating that cognitive abilities remain moderately plastic, even in very old animals. PMID:14584821

  4. Age-Dependent Decline of Endogenous Pain Control: Exploring the Effect of Expectation and Depression

    PubMed Central

    Grashorn, Wiebke; Sprenger, Christian; Forkmann, Katarina; Wrobel, Nathalie; Bingel, Ulrike

    2013-01-01

    Although chronic pain affects all age ranges, it is particularly common in the elderly. One potential explanation for the high prevalence of chronic pain in the older population is impaired functioning of the descending pain inhibitory system which can be studied in humans using conditioned pain modulation (CPM) paradigms. In this study we investigated (i) the influence of age on CPM and (ii) the role of expectations, depression and gender as potential modulating variables of an age-related change in CPM. 64 healthy volunteers of three different age groups (young = 20–40 years, middle-aged = 41–60 years, old = 61–80 years) were studied using a classical CPM paradigm that combined moderate heat pain stimuli to the right forearm as test stimuli (TS) and immersion of the contralateral foot into ice water as the conditioning stimulus (CS). The CPM response showed an age-dependent decline with strong CPM responses in young adults but no significant CPM responses in middle-aged and older adults. These age-related changes in CPM responses could not be explained by expectations of pain relief or depression. Furthermore, changes in CPM responses did not differ between men and women. Our results strongly support the notion of a genuine deterioration of descending pain inhibitory mechanisms with age. PMID:24086595

  5. Age-dependent homeostatic plasticity of GABAergic signaling in developing retinal networks.

    PubMed

    Hennig, Matthias H; Grady, John; van Coppenhagen, James; Sernagor, Evelyne

    2011-08-24

    Developing retinal ganglion cells fire in correlated spontaneous bursts, resulting in propagating waves with robust spatiotemporal features preserved across development and species. Here we investigate the effects of homeostatic adaptation on the circuits controlling retinal waves. Mouse retinal waves were recorded in vitro for up to 35 h with a multielectrode array in presence of the GABA(A) antagonist bicuculline, allowing us to obtain a precise, time-resolved characterization of homeostatic effects in this preparation. Experiments were performed at P4-P6, when GABA(A) signaling is depolarizing in ganglion cells, and at P7-P10, when GABA(A) signaling is hyperpolarizing. At all ages, bicuculline initially increased the wave sizes and other activity metrics. At P5-P6, wave sizes decreased toward control levels within a few hours while firing remained strong, but this ability to compensate disappeared entirely from P7 onwards. This demonstrates that homeostatic control of spontaneous retinal activity maintains specific network dynamic properties in an age-dependent manner, and suggests that the underlying mechanism is linked to GABA(A) signaling. PMID:21865458

  6. Consideration of age-dependent radium retention in people on the basis of the beagle model

    SciTech Connect

    Parks, N.J.; Keane, A.T.

    1981-01-01

    This paper examines in humans the proposition emanating from studies in beagles that long-term retention of radium varies in proportion to the calcium addition rate at the time of intake. Because data on the calcium addition rate in younger humans were fragmentary, human calcium-addition rates were scaled from those in beagles, the relative calcium accretion rates in the two species at equivalent stages of skeletal growth providing the scaling factor. The variation of radium retention with age was determined by fitting a modified power function to data on the retention of radium from about 30 to 15,000 days following a series of therapeutic injections of /sup 226/Ra in humans ranging in age from 18 to 63 yr. The fractional retention R at t days following a single injection of /sup 226/Ra was described by R = (1 + t/d)/sup -0/ /sup 44/. The age-dependent time constant d in the retention function was found to be proportional to the calcium addition rate at the time of injection in subjects receiving < 200 ..mu..g /sup 226/Ra.

  7. Steroidogenic Factor 1 in the Ventromedial Nucleus of the Hypothalamus Regulates Age-Dependent Obesity.

    PubMed

    Kinyua, Ann W; Yang, Dong Joo; Chang, Inik; Kim, Ki Woo

    2016-01-01

    The ventromedial nucleus of the hypothalamus (VMH) is important for the regulation of whole body energy homeostasis and lesions in the VMH are reported to result in massive weight gain. The nuclear receptor steroidogenic factor 1 (SF-1) is a known VMH marker as it is exclusively expressed in the VMH region of the brain. SF-1 plays a critical role not only in the development of VMH but also in its physiological functions. In this study, we generated prenatal VMH-specific SF-1 KO mice and investigated age-dependent energy homeostasis regulation by SF-1. Deletion of SF-1 in the VMH resulted in dysregulated insulin and leptin homeostasis and late onset obesity due to increased food intake under normal chow and high fat diet conditions. In addition, SF-1 ablation was accompanied by a marked reduction in energy expenditure and physical activity and this effect was significantly pronounced in the aged mice. Taken together, our data indicates that SF-1 is a key component in the VMH-mediated regulation of energy homeostasis and implies that SF-1 plays a protective role against metabolic stressors including aging and high fat diet. PMID:27598259

  8. Age-Dependent Demethylation of Sod2 Promoter in the Mouse Femoral Artery

    PubMed Central

    Nguyen, Albert; Leblond, François; Mamarbachi, Maya; Geoffroy, Steve; Thorin, Eric

    2016-01-01

    We studied the age-dependent regulation of the expression of the antioxidant enzyme manganese superoxide dismutase (MnSOD encoded by Sod2) through promoter methylation. C57Bl/6 mice were either (i) sedentary (SED), (ii) treated with the antioxidant catechin (CAT), or (iii) voluntarily exercised (EX) from weaning (1-month old; mo) to 9 mo. Then, all mice aged sedentarily and were untreated until 12 mo. Sod2 promoter methylation was similar in all groups in 9 mo but decreased (p < 0.05) in 12 mo SED mice only, which was associated with an increased (p < 0.05) transcriptional activity in vitro. At all ages, femoral artery endothelial function was maintained; this was due to an increased (p < 0.05) contribution of eNOS-derived NO in 12 mo SED mice only. CAT and EX prevented these changes in age-related endothelial function. Thus, a ROS-dependent epigenetic positive regulation of Sod2 gene expression likely represents a defense mechanism prolonging eNOS function in aging mouse femoral arteries. PMID:26989455

  9. Age-dependent decline in dental pulp regeneration after pulpectomy in dogs.

    PubMed

    Iohara, Koichiro; Murakami, Masashi; Nakata, Kazuhiko; Nakashima, Misako

    2014-04-01

    The age-associated decline in the regenerative abilities of mesenchymal stem cells (MSCs) may be due to age-related changes in reduction in number, intrinsic properties of MSCs and extrinsic factors of the extracellular environment (the stem cell niche). The effect of age on the efficacy of MSC transplantation on regeneration, however, has not been clearly demonstrated due to variable methods of isolation of MSCs and variations in stem cell populations. In this study, dental pulp stem cell (DPSC) subsets were isolated from young and aged dog teeth based on their migratory response to granulocyte-colony stimulating factor (G-CSF) (MDPSCs). In order to study the age-associated changes, their biological properties and stability were compared and the regenerative potential was examined in a pulpectomized tooth model in aged dogs. MDPSCs from aged dogs were efficiently enriched in stem cells, expressing trophic factors with high proliferation, migration and anti-apoptotic effects as in MDPSCs from young dogs. However, pulp regeneration was retarded 120 days after autologous transplantation of aged MDPSCs. We further demonstrated that isolated periodontal ligament stem cells (PDLSCs) from aged dogs, representative of migrating stem cells from outside of the tooth compartment to regenerate pulp tissue, had lower proliferation, migration and anti-apoptotic abilities. These results therefore provide a better understanding of the mechanisms involved in the age-dependent decline in pulp regeneration, which are attributed to a decrease in the regenerative potential of resident stem cells. PMID:24468330

  10. Spatial and Age-Dependent Hair Cell Generation in the Postnatal Mammalian Utricle.

    PubMed

    Gao, Zhen; Kelly, Michael C; Yu, Dehong; Wu, Hao; Lin, Xi; Chi, Fang-Lu; Chen, Ping

    2016-04-01

    Loss of vestibular hair cells is a common cause of balance disorders. Current treatment options for bilateral vestibular dysfunction are limited. During development, atonal homolog 1 (Atoh1) is sufficient and necessary for the formation of hair cells and provides a promising gene target to induce hair cell generation in the mammals. In this study, we used a transgenic mouse line to test the age and cell type specificity of hair cell induction in the postnatal utricle in mice. We found that forced Atoh1 expression in vivo can induce hair cell formation in the utricle from postnatal days 1 to 21, while the efficacy of hair cell induction is progressively reduced as the animals become older. In the utricle, the induction of hair cells occurs both within the sensory region and in cells in the transitional epithelium next to the sensory region. Within the sensory epithelium, the central region, known as the striola, is most subjective to the induction of hair cell formation. Furthermore, forced Atoh1 expression can promote proliferation in an age-dependent manner that mirrors the progressively reduced efficacy of hair cell induction in the postnatal utricle. These results suggest that targeting both cell proliferation and Atoh1 in the utricle striolar region may be explored to induce hair cell regeneration in mammals. The study also demonstrates the usefulness of the animal model that provides an in vivo Atoh1 induction model for vestibular regeneration studies. PMID:25666161

  11. Large-Scale Age-Dependent Skewed Sex Ratio in a Sexually Dimorphic Avian Scavenger

    PubMed Central

    Lambertucci, Sergio A.; Carrete, Martina; Donázar, José Antonio; Hiraldo, Fernando

    2012-01-01

    Age-dependent skewed sex ratios have been observed in bird populations, with adult males generally outnumbering females. This trend is mainly driven by higher female mortality, sometimes associated with anthropogenic factors. Despite the large amount of work on bird sex ratios, research examining the spatial stability of adult sex ratios is extremely scarce. The Andean condor (Vultur gryphus) is the only bird of prey with strong sexual dimorphism favouring males (males are 30% heavier than females). By examining data from most of its South-American range, we show that while the juvenile sex ratio is balanced, or even female-skewed, the sex ratio becomes increasing male-skewed with age, with adult males outnumbering females by >20%, and, in some cases by four times more. This result is consistent across regions and independent of the nature of field data. Reasons for this are unknown but it can be hypothesized that the progressive disappearance of females may be associated with mortality caused by anthropogenic factors. This idea is supported by the asymmetric habitat use by the two sexes, with females scavenging in more humanized areas. Whatever the cause, male-skewed adult sex ratios imply that populations of this endangered scavenger face higher risks of extinction than previously believed. PMID:23029488

  12. Age-Dependent Defects of Regulatory B Cells in Wiskott-Aldrich Syndrome Gene Knockout Mice

    PubMed Central

    Yokoyama, Tadafumi; Yoshizaki, Ayumi; Simon, Karen L.; Kirby, Martha R.; Anderson, Stacie M.; Candotti, Fabio

    2015-01-01

    The Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by recurrent infections, thrombocytopenia, eczema, and high incidence of malignancy and autoimmunity. The cellular mechanisms underlying autoimmune complications in WAS have been extensively studied; however, they remain incompletely defined. We investigated the characteristics of IL-10-producing CD19+CD1dhighCD5+ B cells (CD1dhighCD5+ Breg) obtained from Was gene knockout (WKO) mice and found that their numbers were significantly lower in these mice compared to wild type (WT) controls. Moreover, we found a significant age-dependent reduction of the percentage of IL-10-expressing cells in WKO CD1dhighCD5+ Breg cells as compared to age-matched WT control mice. CD1dhighCD5+ Breg cells from older WKO mice did not suppress the in vitro production of inflammatory cytokines from activated CD4+ T cells. Interestingly, CD1dhighCD5+ Breg cells from older WKO mice displayed a basal activated phenotype which may prevent normal cellular responses, among which is the expression of IL-10. These defects may contribute to the susceptibility to autoimmunity with age in patients with WAS. PMID:26448644

  13. Reproductive and socioeconomic determinants of child survival: confounded, interactive, and age-dependent effects.

    PubMed

    Kost, K; Amin, S

    1992-01-01

    Studies of infant and child mortality have evolved to distinguish between two sets of explanatory variables-factors related to reproductive or maternal characteristics and socioeconomic factors, generally described as characteristics of the family or household. Almost all multivariate analyses include variables from each of these two sets, but there has been little consideration of the relationship between them. We examine how these two sets of variables jointly affect mortality. We test first for confounded effects by examining socioeconomic effects while excluding and then including reproductive variables in nested multivariate models. Next, we look for age-dependent effects among the explanatory variables and find that reproductive and socioeconomic factors affect mortality at differing ages of children. Finally, we examine interactive effects of the two sets of variables. We conclude that the higher mortality observed among the low status groups is not a result of greater concentration of poor reproductive patterns in those groups. Instead, higher status groups probably have more resources available for combating the negative effects of the same high-risk reproductive patterns. PMID:1514117

  14. Accommodating volume-constant age-dependent optical (AVOCADO) model of the crystalline GRIN lens

    PubMed Central

    Sheil, Conor J.; Goncharov, Alexander V.

    2016-01-01

    The purpose of this manuscript is to introduce a new age-dependent model of the human lens with two GRIN power distributions (axial and radial) that allow decoupling of its refractive power and axial optical path length. The aspect ratio of the lens core can be held constant under accommodation, as well as the lens volume by varying the asphericity of the lens external surfaces. The spherical aberration calculated by exact raytracing is shown to be in line with experimental data. The proposed model is compared to previous GRIN models from the literature, and it is concluded that the features of the new model will be useful for GRIN reconstruction in future experimental studies; in particular, studies of the accommodation-dependent properties of the ageing human eye. A proposed logarithmic model of the lens core enables decoupling of three fundamental optical characteristics of the lens, namely axial optical path length, optical power and third-order spherical aberration, without changing the external shape of the lens. Conversely, the near-surface GRIN structure conforms to the external shape of the lens, which is necessary for accommodation modelling. PMID:27231637

  15. Accommodating volume-constant age-dependent optical (AVOCADO) model of the crystalline GRIN lens.

    PubMed

    Sheil, Conor J; Goncharov, Alexander V

    2016-05-01

    The purpose of this manuscript is to introduce a new age-dependent model of the human lens with two GRIN power distributions (axial and radial) that allow decoupling of its refractive power and axial optical path length. The aspect ratio of the lens core can be held constant under accommodation, as well as the lens volume by varying the asphericity of the lens external surfaces. The spherical aberration calculated by exact raytracing is shown to be in line with experimental data. The proposed model is compared to previous GRIN models from the literature, and it is concluded that the features of the new model will be useful for GRIN reconstruction in future experimental studies; in particular, studies of the accommodation-dependent properties of the ageing human eye. A proposed logarithmic model of the lens core enables decoupling of three fundamental optical characteristics of the lens, namely axial optical path length, optical power and third-order spherical aberration, without changing the external shape of the lens. Conversely, the near-surface GRIN structure conforms to the external shape of the lens, which is necessary for accommodation modelling. PMID:27231637

  16. LINC00507 Is Specifically Expressed in the Primate Cortex and Has Age-Dependent Expression Patterns.

    PubMed

    Mills, James D; Ward, Melanie; Chen, Bei Jun; Iyer, Anand M; Aronica, Eleonora; Janitz, Michael

    2016-08-01

    Over the past decade, there has been an increase in the appreciation of the role of non-coding RNA in the development of organism phenotype. It is possible to divide the non-coding elements of the transcriptome into three categories: short non-coding RNAs, circular RNAs and long non-coding RNAs. Long non-coding RNAs are those transcripts that are greater than 200 nts in length and lack any significant open reading frames that produce proteins greater then 100 amino acids. Long intervening non-coding RNAs (lincRNAs) are a subclass of long non-coding RNAs. In contrast to protein coding RNAs, lincRNAs are expressed in a more tissue- and species-specific manner. In particular, many lincRNAs are only conserved amongst higher primates. This coupled with the propensity of many lincRNAs to be expressed in the brain, suggests that they are in fact one of the major drivers of organism complexity. We analysed 39 lincRNAs that are expressed in the frontal cortex and identified LINC00507 as being expressed in a cortex-specific manner in non-human primates and humans. The expression patterns of LINC00507 appear to be age-dependent, suggesting it may be involved in brain development of higher primates. Moreover, the analysis of LINC00507 potential to bind ribosomes revealed that this previously identified non-coding transcript may harbour a micropeptide. PMID:27059230

  17. Microscale Mechanism of Age Dependent Wetting Properties of Prickly Pear Cacti (Opuntia).

    PubMed

    Rykaczewski, Konrad; Jordan, Jacob S; Linder, Rubin; Woods, Erik T; Sun, Xiaoda; Kemme, Nicholas; Manning, Kenneth C; Cherry, Brian R; Yarger, Jeffery L; Majure, Lucas C

    2016-09-13

    Cacti thrive in xeric environments through specialized water storage and collection tactics such as a shallow, widespread root system that maximizes rainwater absorption and spines adapted for fog droplet collection. However, in many cacti, the epidermis, not the spines, dominates the exterior surface area. Yet, little attention has been dedicated to studying interactions of the cactus epidermis with water drops. Surprisingly, the epidermis of plants in the genus Opuntia, also known as prickly pear cacti, has water-repelling characteristics. In this work, we report that surface properties of cladodes of 25 taxa of Opuntia grown in an arid Sonoran climate switch from water-repelling to superwetting under water impact over the span of a single season. We show that the old cladode surfaces are not superhydrophilic, but have nearly vanishing receding contact angle. We study water drop interactions with, as well as nano/microscale topology and chemistry of, the new and old cladodes of two Opuntia species and use this information to uncover the microscopic mechanism underlying this phenomenon. We demonstrate that composition of extracted wax and its contact angle do not change significantly with time. Instead, we show that the reported age dependent wetting behavior primarily stems from pinning of the receding contact line along multilayer surface microcracks in the epicuticular wax that expose the underlying highly hydrophilic layers. PMID:27537082

  18. Effect of pulsed electromagnetic fields on proteoglycan biosynthesis of articular cartilage is age dependent

    PubMed Central

    Bobacz, K; Graninger, W B; Amoyo, L; Smolen, J S

    2006-01-01

    Objective To investigate the effects of a pulsed electromagnetic field (EMF) on articular cartilage matrix biosynthesis with regard to age and cartilage damage using a matrix depleted cartilage explant model. Methods Cartilage explants were obtained from metacarpophalangeal joints of calves and adult cows. After depletion of the extracellular matrix by trypsin digestion, samples were maintained in serum‐free basal medium with and without the addition of interleukin 1β (IL1β). Half the samples were subjected to an EMF for 24 minutes daily; the other half were left untreated. Undigested and untreated explants served as negative controls. After 7 days, biosynthesis of matrix macromolecules was assessed by [35S]sulphate incorporation and values were normalised to hydroxyproline content. Results The EMF increased matrix macromolecule synthesis in undigested, untreated explants (p<0.009). In matrix depleted samples the EMF had no stimulatory effect on proteoglycan biosynthesis. IL1β significantly decreased the de novo synthesis of matrix macromolecules (p<0.00004) in young and adult samples, but an EMF partly counteracted this inhibitory effect in cartilage samples from young, but not old animals. Conclusion EMF promoted matrix macromolecule biosynthesis in intact tissue explants but had no stimulatory effect on damaged articular cartilage. The supressive effects of IL1β were partially counteracted by EMF exposure, exclusively in cartilage derived from young animals. An EMF has age dependent chondroprotective but not structure modifying properties when cartilage integrity is compromised. PMID:16769781

  19. Age-Dependent Susceptibility to Enteropathogenic Escherichia coli (EPEC) Infection in Mice.

    PubMed

    Dupont, Aline; Sommer, Felix; Zhang, Kaiyi; Repnik, Urska; Basic, Marijana; Bleich, André; Kühnel, Mark; Bäckhed, Fredrik; Litvak, Yael; Fulde, Marcus; Rosenshine, Ilan; Hornef, Mathias W

    2016-05-01

    Enteropathogenic Escherichia coli (EPEC) represents a major causative agent of infant diarrhea associated with significant morbidity and mortality in developing countries. Although studied extensively in vitro, the investigation of the host-pathogen interaction in vivo has been hampered by the lack of a suitable small animal model. Using RT-PCR and global transcriptome analysis, high throughput 16S rDNA sequencing as well as immunofluorescence and electron microscopy, we characterize the EPEC-host interaction following oral challenge of newborn mice. Spontaneous colonization of the small intestine and colon of neonate mice that lasted until weaning was observed. Intimate attachment to the epithelial plasma membrane and microcolony formation were visualized only in the presence of a functional bundle forming pili (BFP) and type III secretion system (T3SS). Similarly, a T3SS-dependent EPEC-induced innate immune response, mediated via MyD88, TLR5 and TLR9 led to the induction of a distinct set of genes in infected intestinal epithelial cells. Infection-induced alterations of the microbiota composition remained restricted to the postnatal period. Although EPEC colonized the adult intestine in the absence of a competing microbiota, no microcolonies were observed at the small intestinal epithelium. Here, we introduce the first suitable mouse infection model and describe an age-dependent, virulence factor-dependent attachment of EPEC to enterocytes in vivo. PMID:27159323

  20. Age-Dependent Susceptibility to Enteropathogenic Escherichia coli (EPEC) Infection in Mice

    PubMed Central

    Dupont, Aline; Sommer, Felix; Zhang, Kaiyi; Repnik, Urska; Basic, Marijana; Bleich, André; Kühnel, Mark; Bäckhed, Fredrik; Litvak, Yael; Fulde, Marcus; Rosenshine, Ilan; Hornef, Mathias W.

    2016-01-01

    Enteropathogenic Escherichia coli (EPEC) represents a major causative agent of infant diarrhea associated with significant morbidity and mortality in developing countries. Although studied extensively in vitro, the investigation of the host-pathogen interaction in vivo has been hampered by the lack of a suitable small animal model. Using RT-PCR and global transcriptome analysis, high throughput 16S rDNA sequencing as well as immunofluorescence and electron microscopy, we characterize the EPEC-host interaction following oral challenge of newborn mice. Spontaneous colonization of the small intestine and colon of neonate mice that lasted until weaning was observed. Intimate attachment to the epithelial plasma membrane and microcolony formation were visualized only in the presence of a functional bundle forming pili (BFP) and type III secretion system (T3SS). Similarly, a T3SS-dependent EPEC-induced innate immune response, mediated via MyD88, TLR5 and TLR9 led to the induction of a distinct set of genes in infected intestinal epithelial cells. Infection-induced alterations of the microbiota composition remained restricted to the postnatal period. Although EPEC colonized the adult intestine in the absence of a competing microbiota, no microcolonies were observed at the small intestinal epithelium. Here, we introduce the first suitable mouse infection model and describe an age-dependent, virulence factor-dependent attachment of EPEC to enterocytes in vivo. PMID:27159323

  1. αβγ-Synuclein triple knockout mice reveal age-dependent neuronal dysfunction

    PubMed Central

    Greten-Harrison, Becket; Polydoro, Manuela; Morimoto-Tomita, Megumi; Diao, Ling; Williams, Andrew M.; Nie, Esther H.; Makani, Sachin; Tian, Ning; Castillo, Pablo E.; Buchman, Vladimir L.; Chandra, Sreeganga S.

    2010-01-01

    Synucleins are a vertebrate-specific family of abundant neuronal proteins. They comprise three closely related members, α-, β-, and γ-synuclein. α-Synuclein has been the focus of intense attention since mutations in it were identified as a cause for familial Parkinson's disease. Despite their disease relevance, the normal physiological function of synucleins has remained elusive. To address this, we generated and characterized αβγ-synuclein knockout mice, which lack all members of this protein family. Deletion of synucleins causes alterations in synaptic structure and transmission, age-dependent neuronal dysfunction, as well as diminished survival. Abrogation of synuclein expression decreased excitatory synapse size by ∼30% both in vivo and in vitro, revealing that synucleins are important determinants of presynaptic terminal size. Young synuclein null mice show improved basic transmission, whereas older mice show a pronounced decrement. The late onset phenotypes in synuclein null mice were not due to a loss of synapses or neurons but rather reflect specific changes in synaptic protein composition and axonal structure. Our results demonstrate that synucleins contribute importantly to the long-term operation of the nervous system and that alterations in their physiological function could contribute to the development of Parkinson's disease. PMID:20974939

  2. Consideration of age-dependent radium retention in people on the basis of the beagle model.

    PubMed

    Parks, N J; Keane, A T

    1983-01-01

    This paper examines in humans the proposition emanating from studies in beagles that initial retention of radium varies in proportion to the calcium addition rate at the time of intake. Human calcium addition rates were scaled from those in beagles, the relative calcium accretion rates in the two species at equivalent stages of skeletal growth providing the scaling factor. The variation of radium retention with age was determined by fitting a modified power function to data on the retention of radium from about 30 to 15000 days following a series of therapeutic injections of 226Ra in humans ranging in age from 18 to 63 yr. The fractional retention R at t days following a single injection of 226Ra was described by R = (1 + t/d)-0.44. The age-dependent parameter d in the retention function was found to be proportional to the calcium addition rate at the time of injection in subjects receiving less than 200 micrograms 226Ra. PMID:6862890

  3. Metallothionein modulation in relation to cadmium bioaccumulation and age-dependent sensitivity of Chironomus riparius larvae.

    PubMed

    Toušová, Zuzana; Kuta, Jan; Hynek, David; Adam, Vojtěch; Kizek, René; Bláha, Luděk; Hilscherová, Klára

    2016-06-01

    The goal of this study was to contribute to understanding of the mechanisms behind sensitivity differences between early and late instar larvae of Chironomus riparius and to address the influence of the differences in standard testing approaches on the toxicity evaluation. A 10-day contact sediment toxicity test was carried out to assess sensitivity to cadmium exposure in relation to different age and laboratory culture line origin of test organisms. Chironomid larvae of early (OECD 218 method) and late instar (US-EPA600/R-99/064 method) differed substantially in sensitivity of traditional endpoints (OECD: LOEC 50 and 10 μg Cd/g dry weight (dw); US-EPA: LOEC > 1000 and 100 μg Cd/g dw for survival and growth, respectively). Bioaccumulated cadmium and metallothioneins (MTs) concentrations were analyzed to investigate the role of MTs in reduced sensitivity to cadmium in late instar larvae. Metallothioneins were induced after treatment to greater Cd concentrations, but their levels in relation to cadmium body burdens did not fully explain low sensitivity of late instars to cadmium, which indicates some other effective way of detoxification in late instars. This study brings new information related to the role of MTs in age-dependent toxicant sensitivity and discusses the implications of divergence in data generated by chironomid sediment toxicity tests by standardized methods using different instars. PMID:26957427

  4. Age-dependent neonatal intracerebral hemorrhage in plasminogen activator inhibitor 1 knockout mice.

    PubMed

    Leroux, Philippe; Omouendze, Priscilla L; Roy, Vincent; Dourmap, Nathalie; Gonzalez, Bruno J; Brasse-Lagnel, Carole; Carmeliet, Peter; Leroux-Nicollet, Isabelle; Marret, Stéphane

    2014-05-01

    Intracerebral-intraventricular hemorrhages (ICH/IVH) in very preterm neonates are responsible for high mortality and subsequent disabilities. In humans, tissue plasminogen activator (t-PA) initiates fibrinolysis and activates endoluminal-endothelial receptors; dysfunction of the t-PA inhibitor (PAI-1) results in recurrent hemorrhages. We used PAI-1 knockout (PAI-1) mice to examine the role of t-PA in age-dependent intracranial hemorrhages as a possible model of preterm ICH/IVH. Intracortical injection of 2 μL of phosphate-buffered saline produced a small traumatic injury and a high rate of hemorrhage in PAI-1 pups at postnatal day 3 (P3) or P5, whereas it had no effect in wild-type neonates. This resulted in white matter and cortical lesions, ventricle enlargement, hyperlocomotion, and altered cortical levels of serotonin and dopamine in the adult PAI mice. N-methyl-D-aspartate receptor blockers, plasmin- and matrix metalloproteinases inhibitors reduced hemorrhage and tissue lesions. In contrast to P3 to P5, no significant hemorrhages were induced in P10 PAI-1 pups and there were no behavioral or neurochemical alterations in adulthood. These data suggest that microvascular immaturity up to P5 in mice is a determinant factor required for t-PA-dependent vascular rupture. Neonatal PAI-1 mice could be a useful ICH/IVH model for studying the ontogenic window of vascular immaturity and vascular protection against later neurodisabilities. PMID:24709679

  5. Age-dependence of free radical-induced oxidative damage in ischemic-reperfused rat heart.

    PubMed

    Nagy, K; Takács, I E; Pankucsi, C

    1996-01-01

    Oxygen free radical-induced oxidative damage is involved in both aging and ischemia-reperfusion. The purpose of this study was to determine the aging-induced oxidative alterations in rat heart as well as the age-dependence of heart injury following ischemia-reperfusion. A comparative study was performed on young and old ischemic-reperfused rat hearts. Protein oxidation and the ascorbyl radical level in heart tissue were determined in order to characterize the oxidative stress. Comparing the control conditions, old hearts have 31% more oxidized proteins as measured by protein carbonyl content, and 18% lower ascorbyl radical level as determined by ESR, than young ones. The extent of increase of protein oxidation and ascorbyl free radical depletion induced by ischemia-reperfusion is less pronounced in the old hearts (7 and 8% respectively), as compared to the young ones (55 and 21% respectively). Pre-treatment with a free radical scavenger, such as centrophenoxine, diminished the ischemia-reperfusion injury in both young and old rat hearts. PMID:15374178

  6. Age-dependent Homeostatic Plasticity of GABAergic Signaling in Developing Retinal Networks

    PubMed Central

    Hennig, Matthias H.; Grady, John; van Coppenhagen, James; Sernagor, Evelyne

    2013-01-01

    Developing retinal ganglion cells fire in correlated spontaneous bursts, resulting in propagating waves with robust spatiotemporal features preserved across development and species. Here we investigate the effects of homeostatic adaptation on the circuits controlling retinal waves. Mouse retinal waves were recorded in vitro for up to 35 h with a multielectrode array in presence of the GABAA antagonist bicuculline, allowing us to obtain a precise, time-resolved characterization of homeostatic effects in this preparation. Experiments were performed at P4–P6, when GABAA signaling is depolarizing in ganglion cells, and at P7–P10, when GABAA signaling is hyperpolarizing. At all ages, bicuculline initially increased the wave sizes and other activity metrics. At P5–P6, wave sizes decreased toward control levels within a few hours while firing remained strong, but this ability to compensate disappeared entirely from P7 onwards. This demonstrates that homeostatic control of spontaneous retinal activity maintains specific network dynamic properties in an age-dependent manner, and suggests that the underlying mechanism is linked to GABAA signaling. PMID:21865458

  7. Age-dependent association of serum prolactin with glycaemia and insulin sensitivity in humans.

    PubMed

    Wagner, R; Heni, M; Linder, K; Ketterer, C; Peter, A; Böhm, A; Hatziagelaki, E; Stefan, N; Staiger, H; Häring, H-U; Fritsche, A

    2014-02-01

    The dopamine agonist bromocriptine has been approved for the treatment of type 2 diabetes in the United States. Bromocriptine inhibits prolactin secretion, and patients with hyperprolactinaemia display impaired insulin sensitivity. We therefore hypothesized that low prolactin levels are associated with lower glycaemia and higher insulin sensitivity in healthy subjects. Prolactin levels were determined from fasting serum in participants without diabetes from the cross-sectional Tübingen family study for type 2 diabetes (m/f = 562/1,121, age = 40 ± 13 years, BMI = 30 ± 9 kg/m(2)). A 75 g oral glucose tolerance test was performed, and the area under the glucose curve (AUC(0-120)Glucose) and insulin sensitivity index were calculated. A subgroup (n = 494) underwent hyperinsulinaemic-euglycaemic clamp tests. Prolactin associated positively with insulin sensitivity (p = 0.001, adjusted for gender, age, and BMI). Age strongly interacted (p < 0.0001) with the effect of prolactin on insulin sensitivity, inverting the positive relationship to a negative one in younger participants. Glycated haemoglobin (HbA1c) and AUC(0-120)Glucose correlated negatively with prolactin, and an interaction with age was found as well. Higher prolactin levels are associated with improved insulin sensitivity and lower glucose in individuals without diabetes. This relationship turns to its opposite in younger persons. As prolactin is a proxy for the dopaminergic tone in the central nervous system, these associations may indicate an age-dependent influence of the brain on peripheral insulin sensitivity. PMID:23836327

  8. Age-dependent modulation of vascular niches for haematopoietic stem cells.

    PubMed

    Kusumbe, Anjali P; Ramasamy, Saravana K; Itkin, Tomer; Mäe, Maarja Andaloussi; Langen, Urs H; Betsholtz, Christer; Lapidot, Tsvee; Adams, Ralf H

    2016-04-21

    Blood vessels define local microenvironments in the skeletal system, play crucial roles in osteogenesis and provide niches for haematopoietic stem cells. The properties of niche-forming vessels and their changes in the ageing organism remain incompletely understood. Here we show that Notch signalling in endothelial cells leads to the expansion of haematopoietic stem cell niches in bone, which involves increases in CD31-positive capillaries and platelet-derived growth factor receptor-β (PDGFRβ)-positive perivascular cells, arteriole formation and elevated levels of cellular stem cell factor. Although endothelial hypoxia-inducible factor signalling promotes some of these changes, it fails to enhance vascular niche function because of a lack of arterialization and expansion of PDGFRβ-positive cells. In ageing mice, niche-forming vessels in the skeletal system are strongly reduced but can be restored by activation of endothelial Notch signalling. These findings indicate that vascular niches for haematopoietic stem cells are part of complex, age-dependent microenvironments involving multiple cell populations and vessel subtypes. PMID:27074508

  9. Age-Dependent Changes of the Temporal Order--Causes and Treatment.

    PubMed

    Gubin, Denis G; Weinert, Dietmar; Bolotnova, Tatyana V

    2016-01-01

    This review summarizes current knowledge on deteriorations in temporal order with advanced age. Changes of the overt rhythms will be described but also their putative causes and possible treatments of the disturbances. In aging animals and humans, all rhythm characteristics change. The most prominent changes are a decrease of circadian amplitude, leading to an extra-circadian dissemination (ECD), and a diminished ability to synchronize with the periodic environment. ECD is a shift from circadian to ultradian and infradian frequencies, accompanied by the loss of day-to-day phase stability. Responsiveness to photic and non-photic cues is decreased. As a consequence, both internal and external temporal order are disturbed not only under steady-state conditions but and even more markedly after changes in the periodic environment or following stressful events. Many of the changes seem to occur within the suprachiasmatic nucleus (SCN), the central circadian pacemaker, itself. The number of functioning neurons decreases with advancing age as does the coupling between them. Accordingly, the SCN generates a weaker and less stable circadian signal, insufficient to entrain peripheral oscillators properly or to regulate body functions rhythmically. However, age-dependent disturbances in peripheral organs must also be considered. These changes may occur at different ages, thus causing further internal desynchronization. Several possibilities exist with regard to treating circadian disruptions or at least minimizing their consequences for health and fitness and preventing sleep disturbances. Benefits of bright light, melatonin and other chronobiotics, physical activity, social contacts and regular feeding schedules in preserving the temporal order of aged organisms are discussed. PMID:26632427

  10. Aging-dependent changes in rat heart mitochondrial glutaredoxins--Implications for redox regulation.

    PubMed

    Gao, Xing-Huang; Qanungo, Suparna; Pai, Harish V; Starke, David W; Steller, Kelly M; Fujioka, Hisashi; Lesnefsky, Edward J; Kerner, Janos; Rosca, Mariana G; Hoppel, Charles L; Mieyal, John J

    2013-01-01

    Clinical and animal studies have documented that hearts of the elderly are more susceptible to ischemia/reperfusion damage compared to young adults. Recently we found that aging-dependent increase in susceptibility of cardiomyocytes to apoptosis was attributable to decrease in cytosolic glutaredoxin 1 (Grx1) and concomitant decrease in NF-κB-mediated expression of anti-apoptotic proteins. Besides primary localization in the cytosol, Grx1 also exists in the mitochondrial intermembrane space (IMS). In contrast, Grx2 is confined to the mitochondrial matrix. Here we report that Grx1 is decreased by 50-60% in the IMS, but Grx2 is increased by 1.4-2.6 fold in the matrix of heart mitochondria from elderly rats. Determination of in situ activities of the Grx isozymes from both subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria revealed that Grx1 was fully active in the IMS. However, Grx2 was mostly in an inactive form in the matrix, consistent with reversible sequestration of the active-site cysteines of two Grx2 molecules in complex with an iron-sulfur cluster. Our quantitative evaluations of the active/inactive ratio for Grx2 suggest that levels of dimeric Grx2 complex with iron-sulfur clusters are increased in SSM and IFM in the hearts of elderly rats. We found that the inactive Grx2 can be fully reactivated by sodium dithionite or exogenous superoxide production mediated by xanthine oxidase. However, treatment with rotenone, which generates intramitochondrial superoxide through inhibition of mitochondrial respiratory chain Complex I, did not lead to Grx2 activation. These findings suggest that insufficient ROS accumulates in the vicinity of dimeric Grx2 to activate it in situ. PMID:25126518

  11. Age-dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice.

    PubMed

    Xu, Heping; Chen, Mei; Manivannan, Ayyakkannu; Lois, Noemi; Forrester, John V

    2008-01-01

    Fundus autofluorescence (AF) imaging by confocal scanning laser ophthalmoscopy has been widely used by ophthalmologists in the diagnosis/monitoring of various retinal disorders. It is believed that fundus AF is derived from lipofuscin in retinal pigment epithelial (RPE) cells; however, direct clinicopathological correlation has not been possible in humans. We examined fundus AF by confocal scanning laser ophthalmoscopy and confocal microscopy in normal C57BL/6 mice of different ages. Increasingly strong AF signals were observed with age in the neuroretina and subretinal/RPE layer by confocal scanning laser ophthalmoscopy. Unlike fundus AF detected in normal human subjects, mouse fundus AF appeared as discrete foci distributed throughout the retina. Most of the AF signals in the neuroretina were distributed around retinal vessels. Confocal microscopy of retinal and choroid/RPE flat mounts demonstrated that most of the AF signals were derived from Iba-1+ perivascular and subretinal microglia. An age-dependent accumulation of Iba-1+ microglia at the subretinal space was observed. Lipofuscin granules were detected in large numbers in subretinal microglia by electron microscopy. The number of AF+ microglia and the amount of AF granules/cell increased with age. AF granules/lipofuscin were also observed in RPE cells in mice older than 12 months, but the number of AF+ RPE cells was very low (1.48 mm(-2) and 5.02 mm(-2) for 12 and 24 months, respectively) compared to the number of AF+ microglial cells (20.63 mm(-2) and 76.36 mm(-2) for 6 and 24 months, respectively). The fluorescence emission fingerprints of AF granules in subretinal microglia were the same as those in RPE cells. Our observation suggests that perivascular and subretinal microglia are the main cells producing lipofuscin in normal aged mouse retina and are responsible for in vivo fundus AF. Microglia may play an important role in retinal aging and age-related retinal diseases. PMID:17988243

  12. Tissue- and age-dependent expression of the bovine DEFB103 gene and protein.

    PubMed

    Mirabzadeh-Ardakani, Ali; Solie, Jay; Gonzalez-Cano, Patricia; Schmutz, Sheila M; Griebel, Philip J

    2016-02-01

    Beta-defensin 103 (DEFB103) shares little homology with 8 other members of the bovine beta-defensin family and in other species DEFB103 protein has diverse functions, including antimicrobial activity, a chemoattractant for dendritic cells, enhancing epithelial wound repair and regulating hair colour. Expression of the bovine DEFB103 gene was surveyed in 27 tissues and transcript was most abundant in tissues with stratified squamous epithelium. Oral cavity epithelial tissues and nictitating membrane consistently expressed high levels of DEFB103 gene transcript. An age-dependent decrease (P < 0.05) in DEFB103 gene expression was only observed for buccal epithelium when comparing healthy 10- to 14-day-old and 10- to 12-month-old calves. A bovine herpesvirus-1 respiratory infection did, however, significantly (P < 0.05) up-regulate DEFB103 gene expression in the buccal epithelium of 6- to 8-month-old calves. Finally, DEFB103 transcript was low in lymph nodes draining the skin and at the limit of detection in other internal organs such as lung, intestine and kidney. Affinity-purified rabbit antisera to bovine DEFB103 was used to identify cells expressing DEFB103 protein within tissues with stratified squamous epitheliums. DEFB103 protein was most abundant in basal epithelial cells and was present in these cells prior to birth. Beta-defensins have been identified as regulators of dendritic cell (DC) chemokine responses and we observed a close association between DCs and epithelial cells expressing DEFB103 in both the fetus and newborn calf. In conclusion, bovine DEFB103 gene expression is most abundant in stratified squamous epithelium with DEFB103 protein localised to basal epithelial cells. These observations are consistent with proposed roles for DEFB103 in DC recruitment and repair of stratified squamous epithelium. PMID:26299200

  13. Age-dependent expression of the erythropoietin gene in rat liver and kidneys.

    PubMed Central

    Eckardt, K U; Ratcliffe, P J; Tan, C C; Bauer, C; Kurtz, A

    1992-01-01

    Using RNAse protection, we have made quantitative measurements of erythropoietin (EPO) mRNA in liver and kidneys of developing rats (days 1-54), to determine the relative contribution of both organs to the total EPO mRNA, to monitor changes which occur with development, and to compare the hypoxia-induced accumulation of EPO mRNA with the changes in serum EPO concentrations. To determine whether developmental and organ-specific responsiveness is related to the type of hypoxic stimulus, normobaric hypoxia was compared with exposure to carbon monoxide (functional anemia). Under both stimuli EPO mRNA concentration in liver was maximal on day 7 and declined during development. In contrast, EPO mRNA concentration in kidney increased during development from day 1 when it was 30-65% the hepatic concentration to day 54 when it was 12-fold higher than in liver. When organ weight was considered the liver was found to contain the majority of EPO mRNA in the first three to four weeks of life, and although, in stimulated animals, the hepatic proportion declined from 85-91% on day 1, it remained approximately 33% at day 54 and was similar for the two types of stimuli. When normalized for body weight the sum of renal and hepatic EPO mRNA in animals of a particular age was related linearly to serum hormone concentrations. However, the slope of this regression increased progressively with development, suggesting age-dependent alterations in translational efficiency or EPO metabolism. Images PMID:1541670

  14. Age-dependent uncoupling of mitochondria from Ca2+ release units in skeletal muscle

    PubMed Central

    Ainbinder, Alina; Michelucci, Antonio; Kern, Helmut; Dirksen, Robert T.; Boncompagni, Simona; Protasi, Feliciano

    2015-01-01

    Calcium release units (CRUs) and mitochondria control myoplasmic [Ca2+] levels and ATP production in muscle, respectively. We recently reported that these two organelles are structurally connected by tethers, which promote proximity and proper Ca2+ signaling. Here we show that disposition, ultrastructure, and density of CRUs and mitochondria and their reciprocal association are compromised in muscle from aged mice. Specifically, the density of CRUs and mitochondria is decreased in muscle fibers from aged (>24 months) vs. adult (3-12 months), with an increased percentage of mitochondria being damaged and misplaced from their normal triadic position. A significant reduction in tether (13.8±0.4 vs. 5.5±0.3 tethers/100μm2) and CRU-mitochondrial pair density (37.4±0.8 vs. 27.0±0.7 pairs/100μm2) was also observed in aged mice. In addition, myoplasmic Ca2+ transient (1.68±0.08 vs 1.37±0.03) and mitochondrial Ca2+ uptake (9.6±0.050 vs 6.58±0.54) during repetitive high frequency tetanic stimulation were significantly decreased. Finally oxidative stress, assessed from levels of 3-nitrotyrosine (3-NT), Cu/Zn superoxide-dismutase (SOD1) and Mn superoxide dismutase (SOD2) expression, were significantly increased in aged mice. The reduced association between CRUs and mitochondria with aging may contribute to impaired cross-talk between the two organelles, possibly resulting in reduced efficiency in activity-dependent ATP production and, thus, to age-dependent decline of skeletal muscle performance. PMID:26485763

  15. Ankyrin-B metabolic syndrome combines age-dependent adiposity with pancreatic β cell insufficiency

    PubMed Central

    Lorenzo, Damaris N.; Healy, Jane A.; Hostettler, Janell; Davis, Jonathan; Yang, Jiayu; Wang, Chao; Hohmeier, Hans Ewald; Zhang, Mingjie; Bennett, Vann

    2015-01-01

    Rare functional variants of ankyrin-B have been implicated in human disease, including hereditary cardiac arrhythmia and type 2 diabetes (T2D). Here, we developed murine models to evaluate the metabolic consequences of these alterations in vivo. Specifically, we generated knockin mice that express either the human ankyrin-B variant R1788W, which is present in 0.3% of North Americans of mixed European descent and is associated with T2D, or L1622I, which is present in 7.5% of African Americans. Young AnkbR1788W/R1788W mice displayed primary pancreatic β cell insufficiency that was characterized by reduced insulin secretion in response to muscarinic agonists, combined with increased peripheral glucose uptake and concomitantly increased plasma membrane localization of glucose transporter 4 (GLUT4) in skeletal muscle and adipocytes. In contrast, older AnkbR1788W/R1788W and AnkbL1622I/L1622I mice developed increased adiposity, a phenotype that was reproduced in cultured adipocytes, and insulin resistance. GLUT4 trafficking was altered in animals expressing mutant forms of ankyrin-B, and we propose that increased cell surface expression of GLUT4 in skeletal muscle and fatty tissue of AnkbR1788W/R1788W mice leads to the observed age-dependent adiposity. Together, our data suggest that ankyrin-B deficiency results in a metabolic syndrome that combines primary pancreatic β cell insufficiency with peripheral insulin resistance and is directly relevant to the nearly one million North Americans bearing the R1788W ankyrin-B variant. PMID:26168218

  16. Age-dependence of sensorimotor and cerebral electroencephalographic asymmetry in rats subjected to unilateral cerebrovascular stroke

    PubMed Central

    2013-01-01

    Background The human population mostly affected by stroke is more than 65 years old. This study was designed to meet the recommendation that models of cerebral ischemia in aged animals are more relevant to the clinical setting than young animal models. Until now the majority of the pre-clinical studies examining age effects on stroke outcomes have used rats of old age. Considering the increasing incidence of stroke among younger than old human population, new translational approaches in animal models are needed to match the rejuvenation of stroke. A better knowledge of alterations in stroke outcomes in middle-aged rats has important preventive and management implications providing clues for future investigations on effects of various neuroprotective and neurorestorative drugs against cerebrovascular accidents that may occur before late senescence. Methods We evaluated the impact of transient focal ischemia, induced by intracerebral unilateral infusion of endothelin-1 (Et-1) near the middle cerebral artery of conscious rats, on volume of brain damage and asymmetry in behavioral and electroencephalographic (EEG) output measures in middle-aged (11–12 month-old) rats. Results We did not find any age-dependent difference in the volume of ischemic brain damage three days after Et-1 infusion. However, age was an important determinant of neurological and EEG outcomes after stroke. Middle-aged ischemic rats had more impaired somatosensory functions of the contralateral part of the body than young ischemic rats and thus, had greater left-right reflex/sensorimotor asymmetry. Interhemispheric EEG asymmetry was more evident in middle-aged than in young ischemic rats, and this could tentatively explain the behavioral asymmetry. Conclusions With a multiparametric approach, we have validated the endothelin model of ischemia in middle-aged rats. The results provide clues for future studies on mechanisms underlying plasticity after brain damage and motivate investigations of

  17. Age-Dependent Kinetics and Metabolism of Dichloroacetate: Possible Relevance to Toxicity

    PubMed Central

    Shroads, Albert L.; Guo, Xu; Dixit, Vaishali; Liu, Hui-Ping; James, Margaret O.; Stacpoole, Peter W.

    2008-01-01

    Dichloroacetate (DCA) is an investigational drug for certain metabolic diseases. It is biotransformed principally by the ζ-1 family isoform of glutathione transferase (GSTz1), also known as maleylacetoacetate isomerase (MAAI), which catalyzes the penultimate step in tyrosine catabolism. DCA causes a reversible peripheral neuropathy in several species, including humans. However, recent clinical trials indicate that adults are considerably more susceptible to this adverse effect than children. We evaluated the kinetics and biotransformation of DCA and its effects on tyrosine metabolism in nine patients treated for 6 months with 25 mg/kg/day and in rats treated for 5 days with 50 mg/kg/day. We also measured the activity and expression of hepatic GSTz1/MAAI. Chronic administration of DCA causes a striking age-dependent decrease in its plasma clearance and an increase in its plasma half-life in patients and rats. Urinary excretion of unchanged DCA in rats increases with age, whereas oxalate, an end product of DCA metabolism, shows the opposite trend. Low concentrations of monochloroacetate (MCA), which is known to be neurotoxic, increase as a function of age in the urine of dosed rats. MCA was detectable in plasma only of older animals. Hepatic GSTz1/MAAI-specific activity was inhibited equally by DCA treatment among all age groups, whereas plasma and urinary levels of maleylacetone, a natural substrate for this enzyme, increased with age. We conclude that age is an important variable in the in vivo metabolism and elimination of DCA and that it may account, in part, for the neurotoxicity of this compound in humans and other species. PMID:18096758

  18. Elevated systolic blood pressure in male GH transgenic mice is age dependent.

    PubMed

    Jara, Adam; Benner, Chance M; Sim, Don; Liu, Xingbo; List, Edward O; Householder, Lara A; Berryman, Darlene E; Kopchick, John J

    2014-03-01

    Acromegaly is associated with an increased incidence of cardiovascular disease. Transgenic mice expressing bovine GH (bGH) gene have previously been used to examine the effects of chronic GH stimulation on cardiovascular function. Results concerning systolic blood pressure (SBP) in bGH mice are conflicting. We hypothesized that these discrepancies may be the result of the various ages of the mice used in previous studies. In the current study, SBP was assessed monthly in male bGH mice from 3-12 months of age. Factors known to alter blood pressure were assessed during this time and included: levels of brain natriuretic peptide (BNP) and glucose homeostasis markers, and renal levels of angiotensin-converting enzyme 2 and endothelial nitric oxide synthase. Beginning at 6 months of age bGH had increased SBP compared with wild-type controls, which remained elevated through 12 months of age. Despite having increased blood pressure and cardiac BNP mRNA, bGH mice had decreased circulating levels of BNP. Additionally, bGH mice had an age-dependent decline in insulin levels. For example, they were hyperinsulinemic at 3 months, but by 11 months of age were hypoinsulinemic relative to wild-type controls. This decrease in insulin was accompanied by improved glucose tolerance at 11 months. Finally, both angiotensin-converting enzyme 2 and endothelial nitric oxide synthase expression were severely depressed in kidneys of 11-month-old bGH mice. These results indicate that elevated SBP in bGH mice is dependent on age, independent of insulin resistance, and related to alterations in both the natriuretic peptide and renin-angiotensin systems. PMID:24424040

  19. Fmr1 deficiency promotes age-dependent alterations in the cortical synaptic proteome

    PubMed Central

    Tang, Bin; Wang, Tingting; Wan, Huida; Han, Li; Qin, Xiaoyan; Zhang, Yaoyang; Wang, Jian; Yu, Chunlei; Berton, Fulvia; Francesconi, Walter; Yates, John R.; Vanderklish, Peter W.; Liao, Lujian

    2015-01-01

    Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder characterized by severe intellectual disability and other symptoms including autism. Although caused by the silencing of a single gene, Fmr1 (fragile X mental retardation 1), the complexity of FXS pathogenesis is amplified because the encoded protein, FMRP, regulates the activity-dependent translation of numerous mRNAs. Although the mRNAs that associate with FMRP have been extensively studied, little is known regarding the proteins whose expression levels are altered, directly or indirectly, by loss of FMRP during brain development. Here we systematically measured protein expression in neocortical synaptic fractions from Fmr1 knockout (KO) and wild-type (WT) mice at both adolescent and adult stages. Although hundreds of proteins are up-regulated in the absence of FMRP in young mice, this up-regulation is largely diminished in adulthood. Up-regulated proteins included previously unidentified as well as known targets involved in synapse formation and function and brain development and others linked to intellectual disability and autism. Comparison with putative FMRP target mRNAs and autism susceptibility genes revealed substantial overlap, consistent with the idea that the autism endophenotype of FXS is due to a “multiple hit” effect of FMRP loss, particularly within the PSD95 interactome. Through studies of de novo protein synthesis in primary cortical neurons from KO and WT mice, we found that neurons lacking FMRP produce nascent proteins at higher rates, many of which are synaptic proteins and encoded by FMRP target mRNAs. Our results provide a greatly expanded view of protein changes in FXS and identify age-dependent effects of FMRP in shaping the neuronal proteome. PMID:26307763

  20. Age-dependent variation of the Gradient Index profile in human crystalline lenses

    PubMed Central

    de Castro, A.; Siedlecki, D.; Borja, David; Uhlhorn, Stephen; Parel, Jean-Marie; Manns, Fabrice; Marcos, S.

    2011-01-01

    Purpose To reconstruct the gradient index (GRIN) profile of human crystalline lenses ex-vivo using Optical Coherence Tomography (OCT) imaging with an optimization technique and to study the dependence of the GRIN profile with age. Methods Cross-sectional images of nine isolated human crystalline lenses with ages ranging from 6 to 72 (post mortem time 1 to 4 days) were obtained using a custom-made OCT system. Lenses were extracted from whole cadaver globes and placed in a measurement chamber filled with preservation medium (DMEM). Lenses were imaged with the anterior surface up and then flipped over and imaged again, to obtain posterior lens surface profiles both undistorted and distorted by the refraction through the anterior crystalline lens and GRIN. The GRIN distribution of the lens was described with three variables by means of power function, with variables being the nucleus and surface index, and a power coefficient that describes the decay of the refractive index from the nucleus to the surface. An optimization method was used to search for the parameters that produced the best match of the distorted posterior surface. Results The distorted surface was simulated with accuracy around the resolution of the OCT system (under 15 µm). The reconstructed refractive index values ranged from 1.356 to 1.388 for the surface, and from 1.396 to 1.434 for the nucleus. The power coefficient ranged between 3 and 18. The power coefficient increased significantly with age, at a rate of 0.24 per year. Conclusion Optical Coherence Tomography allowed optical, non-invasive measurement of the 2-D gradient index profile of the isolated human crystalline lens ex vivo. The age-dependent variation of the changes is consistent with previous data using magnetic resonance imaging, and the progressive formation of a refractive index plateau. PMID:22865954

  1. Leptin is involved in age-dependent changes in response to systemic inflammation in the rat.

    PubMed

    Koenig, Sandy; Luheshi, Giamal N; Wenz, Tina; Gerstberger, Rüdiger; Roth, Joachim; Rummel, Christoph

    2014-02-01

    Obesity contributes to a state of subclinical peripheral and central inflammation and is often associated with aging. Here we investigated the source and contribution of adipose tissue derived cytokines and the cytokine-like hormone leptin to age-related changes in lipopolysaccharide (LPS)-induced brain-controlled sickness-responses. Old (24 months) and young (2 months) rats were challenged with LPS or saline alone or in combination with a neutralizing leptin antiserum (LAS) or control serum. Changes in the sickness-response were monitored by biotelemetry. Additionally, ex vivo fat-explants from young and old rats were stimulated with LPS or saline and culture medium collected and analyzed by cytokine-specific bioassays/ELISAs. We found enhanced duration/degree of the sickness-symptoms, including delayed but prolonged fever in old rats. This response was accompanied by increased plasma-levels of interleukin (IL)-6 and IL-1ra and exaggerated expression of inflammatory markers in brain and liver analyzed by RT-PCR including inhibitor κBα, microsomal prostaglandin synthase and cyclooxygenase 2 (brain). Moreover, for the first time, we were able to show prolonged elevated plasma leptin-levels in LPS-treated old animals. Treatment with LAS in young rats tended to attenuate the early- and in old rats the prolonged febrile response. Fat-explants exhibited unchanged IL-6 but reduced IL-1ra and tumor necrosis factor (TNF)-α release from adipose tissue of aged compared to young animals. In addition, we found increased expression of the endogenous immune regulator microRNA146a in aged animals suggesting a role for these mediators in counteracting brain inflammation. Overall, our results indicate a role of adipose tissue and leptin in “aging-related-inflammation” and age-dependent modifications of febrile-responses. PMID:24513873

  2. G-CSF enhances resolution of Staphylococcus aureus wound infection in an age-dependent manner.

    PubMed

    Brubaker, Aleah L; Kovacs, Elizabeth J

    2013-10-01

    This study tested the hypothesis that heightened bacterial colonization and delayed wound closure in aged mice could be attenuated by granulocyte colony-stimulating factor (G-CSF) treatment. Previously, we reported that aged mice had elevated bacterial levels, protracted wound closure, and reduced wound neutrophil accumulation after Staphylococcus aureus wound infection relative to young mice. In aseptic wound models, G-CSF treatment improved wound closure in aged mice to rates observed in young mice. Given these data, our objective was to determine if G-CSF could restore age-associated differences in wound bacterial burden and closure by increasing wound neutrophil recruitment. Young (3- to 4-month) and aged (18- to 20-month) BALB/c mice received three dorsal subcutaneous injections of G-CSF (250 ng/50 μL per injection) or saline control (50 μL per injection) 30 min after wound infection. Mice were killed at days 3 and 7 after wound infection, and bacterial colonization, wound size, wound leukocyte accumulation, and peripheral blood were evaluated. At days 3 and 7 after wound infection, bacterial colonization was significantly reduced in G-CSF-treated aged mice to levels observed in saline-treated young animals. Wound size was reduced in G-CSF-treated aged animals, with no effect on wound size in G-CSF-treated young mice. Local G-CSF treatment significantly enhanced neutrophil wound accumulation in aged mice, whereas there was no G-CSF-induced change in young mice. These data demonstrate that G-CSF enhances bacterial clearance and wound closure in an age-dependent manner. Moreover, G-CSF may be of therapeutic potential in the setting of postoperative wound infection or chronic nonhealing wounds in elderly patients. PMID:23856924

  3. Age-dependent variation of the gradient index profile in human crystalline lenses

    NASA Astrophysics Data System (ADS)

    de Castro, Alberto; Siedlecki, Damian; Borja, David; Uhlhorn, Stephen; Parel, Jean-Marie; Manns, Fabrice; Marcos, Susana

    2011-11-01

    An investigation was carried out with the aim of reconstructing the gradient index (GRIN) profile of human crystalline lenses ex-vivo using optical coherence tomography (OCT) imaging with an optimization technique and to study the dependence of the GRIN profile with age. Cross-sectional images of nine isolated human crystalline lenses with ages ranging from 6 to 72 (post-mortem time 1 to 4 days) were obtained using a custom-made OCT system. Lenses were extracted from whole cadaver globes and placed in a measurement chamber filled with preservation medium (DMEM). Lenses were imaged with the anterior surface up and then flipped over and imaged again, to obtain posterior lens surface profiles both undistorted and distorted by the refraction through the anterior crystalline lens and GRIN. The GRIN distribution of the lens was described with three variables by means of power function, with variables being the nucleus and surface index, and a power coefficient that describes the decay of the refractive index from the nucleus to the surface. An optimization method was used to search for the parameters that produced the best match of the distorted posterior surface. The distorted surface was simulated with accuracy around the resolution of the OCT system (under 15 µm). The reconstructed refractive index values ranged from 1.356 to 1.388 for the surface, and from 1.396 to 1.434 for the nucleus. The power coefficient ranged between 3 and 18. The power coefficient increased significantly with age, at a rate of 0.24 per year. Optical coherence tomography allowed optical, non-invasive measurement of the 2D gradient index profile of the isolated human crystalline lens ex vivo. The age-dependent variation of the changes is consistent with previous data using magnetic resonance imaging, and the progressive formation of a refractive index plateau.

  4. Is Growth Differentiation Factor 11 a Realistic Therapeutic for Aging-Dependent Muscle Defects?

    PubMed

    Harper, Shavonn C; Brack, Andrew; MacDonnell, Scott; Franti, Michael; Olwin, Bradley B; Bailey, Beth A; Rudnicki, Michael A; Houser, Steven R

    2016-04-01

    This "Controversies in Cardiovascular Research" article evaluates the evidence for and against the hypothesis that the circulating blood level of growth differentiation factor 11 (GDF11) decreases in old age and that restoring normal GDF11 levels in old animals rejuvenates their skeletal muscle and reverses pathological cardiac hypertrophy and cardiac dysfunction. Studies supporting the original GDF11 hypothesis in skeletal and cardiac muscle have not been validated by several independent groups. These new studies have either found no effects of restoring normal GDF11 levels on cardiac structure and function or have shown that increasing GDF11 or its closely related family member growth differentiation factor 8 actually impairs skeletal muscle repair in old animals. One possible explanation for what seems to be mutually exclusive findings is that the original reagent used to measure GDF11 levels also detected many other molecules so that age-dependent changes in GDF11 are still not well known. The more important issue is whether increasing blood [GDF11] repairs old skeletal muscle and reverses age-related cardiac pathologies. There are substantial new and existing data showing that GDF8/11 can exacerbate rather than rejuvenate skeletal muscle injury in old animals. There is also new evidence disputing the idea that there is pathological hypertrophy in old C57bl6 mice and that GDF11 therapy can reverse cardiac pathologies. Finally, high [GDF11] causes reductions in body and heart weight in both young and old animals, suggestive of a cachexia effect. Our conclusion is that elevating blood levels of GDF11 in the aged might cause more harm than good. PMID:27034276

  5. Bayesian quantitative trait locus mapping using inferred haplotypes.

    PubMed

    Durrant, Caroline; Mott, Richard

    2010-03-01

    We describe a fast hierarchical Bayesian method for mapping quantitative trait loci by haplotype-based association, applicable when haplotypes are not observed directly but are inferred from multiple marker genotypes. The method avoids the use of a Monte Carlo Markov chain by employing priors for which the likelihood factorizes completely. It is parameterized by a single hyperparameter, the fraction of variance explained by the quantitative trait locus, compared to the frequentist fixed-effects model, which requires a parameter for the phenotypic effect of each combination of haplotypes; nevertheless it still provides estimates of haplotype effects. We use simulation to show that the method matches the power of the frequentist regression model and, when the haplotypes are inferred, exceeds it for small QTL effect sizes. The Bayesian estimates of the haplotype effects are more accurate than the frequentist estimates, for both known and inferred haplotypes, which indicates that this advantage is independent of the effect of uncertainty in haplotype inference and will hold in comparison with frequentist methods in general. We apply the method to data from a panel of recombinant inbred lines of Arabidopsis thaliana, descended from 19 inbred founders. PMID:20048050

  6. Factors affecting the power of haplotype markers in association studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An important, unresolved question in genome-wide association studies is whether there are predictable differences in power between single-SNP and haplotype markers. In this study, we use coalescent simulations to compare power for single-SNP and haplotype markers under a number of different models ...

  7. Use of haplotypes to predict selection limits and Mendelian sampling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Limits to selection and Mendelian sampling terms can be calculated using haplotypes, which are sums of individual additive effects on a chromosome. Haplotypes were imputed for 43,385 actual markers of 3,765 Jerseys using the Fortran program findhap.f90, which combines population and pedigree haploty...

  8. iXora1: exact haplotype inferencing and trait association

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: We address the task of extracting accurate haplotypes from genotype data of individuals of large F1 populations for mapping studies. While methods for inferring parental haplotype assignments on large F1 populations exist in theory, these approaches do not work in practice at high levels...

  9. Reconstruction of N-acetyltransferase 2 haplotypes using PHASE.

    PubMed

    Golka, Klaus; Blaszkewicz, Meinolf; Samimi, Mirabutaleb; Bolt, Hermann M; Selinski, Silvia

    2008-04-01

    The genotyping of N-acetyltransferase 2 (NAT2) by PCR/RFLP methods yields in a considerable percentage ambiguous results. To resolve this methodical problem a statistical approach was applied. PHASE v2.1.1, a statistical program for haplotype reconstruction was used to estimate haplotype pairs from NAT2 genotyping data, obtained by the analysis of seven single nucleotide polymorphisms relevant for Caucasians. In 1,011 out of 2,921 (35%) subjects the haplotype pairs were clearcut by the PCR/RFLP data only. For the majority of the data the applied method resulted in a multiplicity (2-4) of possible haplotype pairs. Haplotype reconstruction using PHASE v2.1.1 cleared this ambiguity in all cases but one, where an alternative haplotype pair was considered with a probability of 0.029. The estimation of the NAT2 haplotype is important because the assignment of the NAT2 alleles *12A, *12B, *12C or *13 to the rapid or slow NAT2 genotype has been discussed controversially. A clear assignment is indispensable in surveys of human bladder cancer caused by aromatic amine exposures. In conclusion, PHASE v2.1.1 software allowed an unambiguous haplotype reconstruction in 2,920 of 2,921 cases (>99.9%). PMID:17879084

  10. Restriction digestion method for haplotyping the potato psyllid, Bactericera cockerelli

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A restriction digestion method has been developed for haplotyping the potato psyllid, Bactericera cockerelli Sulc., an economically important pest of solanaceous crops. This method differentiates the four known potato psyllid haplotypes by utilizing restriction enzyme digestion of a portion of the ...

  11. Mathematical properties and bounds on haplotyping populations by pure parsimony.

    PubMed

    Wang, I-Lin; Chang, Chia-Yuan

    2011-06-01

    Although the haplotype data can be used to analyze the function of DNA, due to the significant efforts required in collecting the haplotype data, usually the genotype data is collected and then the population haplotype inference (PHI) problem is solved to infer haplotype data from genotype data for a population. This paper investigates the PHI problem based on the pure parsimony criterion (HIPP), which seeks the minimum number of distinct haplotypes to infer a given genotype data. We analyze the mathematical structure and properties for the HIPP problem, propose techniques to reduce the given genotype data into an equivalent one of much smaller size, and analyze the relations of genotype data using a compatible graph. Based on the mathematical properties in the compatible graph, we propose a maximal clique heuristic to obtain an upper bound, and a new polynomial-sized integer linear programming formulation to obtain a lower bound for the HIPP problem. PMID:21354185

  12. Haplotype map of sickle cell anemia in Tunisia.

    PubMed

    Moumni, Imen; Ben Mustapha, Maha; Sassi, Sarra; Zorai, Amine; Ben Mansour, Ikbel; Douzi, Kais; Chouachi, Dorra; Mellouli, Fethi; Bejaoui, Mohamed; Abbes, Salem

    2014-01-01

    β-Globin haplotypes are important to establish the ethnic origin and predict the clinical development of sickle cell disease patients (SCD). To determine the chromosomal background of β (S) Tunisian sickle cell patients, in this first study in Tunisia, we have explored four polymorphic regions of β-globin cluster on chromosome 11. It is the 5' region of β-LCR-HS2 site, the intervening sequence II (IVSII) region of two fetal ((G)γ and (A)γ) genes and the 5' region of β-globin gene. The results reveal a high molecular diversity of a microsatellite configuration describing the sequences haplotypes. The linkage disequilibrium analysis showed various haplotype combinations giving 22 "extended haplotypes". These results confirm the utility of the β-globin haplotypes for population studies and contribute to knowledge of the Tunisian gene pool, as well as establishing the role of genetic markers in physiopathology of SCD. PMID:25197158

  13. Chromosomal Haplotypes by Genetic Phasing of Human Families

    PubMed Central

    Roach, Jared C.; Glusman, Gustavo; Hubley, Robert; Montsaroff, Stephen Z.; Holloway, Alisha K.; Mauldin, Denise E.; Srivastava, Deepak; Garg, Vidu; Pollard, Katherine S.; Galas, David J.; Hood, Leroy; Smit, Arian F.A.

    2011-01-01

    Assignment of alleles to haplotypes for nearly all the variants on all chromosomes can be performed by genetic analysis of a nuclear family with three or more children. Whole-genome sequence data enable deterministic phasing of nearly all sequenced alleles by permitting assignment of recombinations to precise chromosomal positions and specific meioses. We demonstrate this process of genetic phasing on two families each with four children. We generate haplotypes for all of the children and their parents; these haplotypes span all genotyped positions, including rare variants. Misassignments of phase between variants (switch errors) are nearly absent. Our algorithm can also produce multimegabase haplotypes for nuclear families with just two children and can handle families with missing individuals. We implement our algorithm in a suite of software scripts (Haploscribe). Haplotypes and family genome sequences will become increasingly important for personalized medicine and for fundamental biology. PMID:21855840

  14. A haplotype map of the human genome

    PubMed Central

    2007-01-01

    Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution. PMID:16255080

  15. General Framework for Meta-Analysis of Haplotype Association Tests.

    PubMed

    Wang, Shuai; Zhao, Jing Hua; An, Ping; Guo, Xiuqing; Jensen, Richard A; Marten, Jonathan; Huffman, Jennifer E; Meidtner, Karina; Boeing, Heiner; Campbell, Archie; Rice, Kenneth M; Scott, Robert A; Yao, Jie; Schulze, Matthias B; Wareham, Nicholas J; Borecki, Ingrid B; Province, Michael A; Rotter, Jerome I; Hayward, Caroline; Goodarzi, Mark O; Meigs, James B; Dupuis, Josée

    2016-04-01

    For complex traits, most associated single nucleotide variants (SNV) discovered to date have a small effect, and detection of association is only possible with large sample sizes. Because of patient confidentiality concerns, it is often not possible to pool genetic data from multiple cohorts, and meta-analysis has emerged as the method of choice to combine results from multiple studies. Many meta-analysis methods are available for single SNV analyses. As new approaches allow the capture of low frequency and rare genetic variation, it is of interest to jointly consider multiple variants to improve power. However, for the analysis of haplotypes formed by multiple SNVs, meta-analysis remains a challenge, because different haplotypes may be observed across studies. We propose a two-stage meta-analysis approach to combine haplotype analysis results. In the first stage, each cohort estimate haplotype effect sizes in a regression framework, accounting for relatedness among observations if appropriate. For the second stage, we use a multivariate generalized least square meta-analysis approach to combine haplotype effect estimates from multiple cohorts. Haplotype-specific association tests and a global test of independence between haplotypes and traits are obtained within our framework. We demonstrate through simulation studies that we control the type-I error rate, and our approach is more powerful than inverse variance weighted meta-analysis of single SNV analysis when haplotype effects are present. We replicate a published haplotype association between fasting glucose-associated locus (G6PC2) and fasting glucose in seven studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and we provide more precise haplotype effect estimates. PMID:27027517

  16. Identity of the mtDNA haplotype(s) of Phytophthora infestans in historical specimens from the Irish potato famine.

    PubMed

    May, Kimberley Jane; Ristaino, Jean Beagle

    2004-05-01

    The mtDNA haplotypes of the plant pathogen Phytophthora infestans present in dried potato and tomato leaves from herbarium specimens collected during the Irish potato famine and later in the 19th and early 20th century were identified. A 100 bp fragment of ribosomal DNA (rDNA) specific for P. infestans was amplified from 90% of the specimens (n = 186), confirming infection by P. infestans. Primers were designed that distinguish the extant mtDNA haplotypes. 86% percent of the herbarium specimens from historic epidemics were infected with the Ia mtDNA haplotype. Two mid-20th century potato leaves from Ecuador (1967) and Bolivia (1944) were infected with the Ib mtDNA haplotype of the pathogen. Both the Ia and IIb haplotypes were found in specimens collected in Nicaragua in the 1950s. The data suggest that the Ia haplotype of P. infestans was responsible for the historic epidemics during the 19th century in the UK, Europe, and the USA. The Ib mtDNA haplotype of the pathogen was dispersed later in the early 20th century from Bolivia and Ecuador. Multiple haplotypes were present outside Mexico in the 1940s-60s, indicating that pathogen diversity was greater than previously believed. PMID:15229999

  17. Age-dependent enhancement of inhibitory synaptic transmission in CA1 pyramidal neurons via GluR5 kainate receptors.

    PubMed

    Xu, Changqing; Cui, Changhai; Alkon, Daniel L

    2009-08-01

    Changes in hippocampal synaptic networks during aging may contribute to age-dependent compromise of cognitive functions such as learning and memory. Previous studies have demonstrated that GABAergic synaptic transmission exhibits age-dependent changes. To better understand such age-dependent changes of GABAergic synaptic inhibition, we performed whole-cell recordings from pyramidal cells in the CA1 area of acute hippocampal slices on aged (24-26 months old) and young (2-4 months old) Brown-Norway rats. We found that the frequency and amplitude of spontaneous inhibitory postsynaptic current (IPSCs) were significantly increased in aged rats, but the frequency and amplitude of mIPSCs were decreased. Furthermore, the regulation of GABAergic synaptic transmission by GluR5 containing kainate receptors was enhanced in aged rats, which was revealed by using LY382884 (a GluR5 kainate receptor antagonist) and ATPA (a GluR5 kainate receptor agonist). Moreover, we demonstrated that vesicular glutamate transporters are involved in the kainate receptor dependent regulation of sIPSCs. Taken together, these results suggest that GABAergic synaptic transmission is potentiated in aged rats, and GluR5 containing kainate receptors regulate the inhibitory synaptic transmission through endogenous glutamate. These alterations of GABAergic input with aging could contribute to age-dependent cognitive decline. PMID:19123252

  18. Loss of prion protein leads to age-dependent behavioral abnormalities and changes in cytoskeletal protein expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cellular prion protein (PrPC) is a multifunctional protein, whose exact physiological role remains elusive. Since previous studies indicated a neuroprotective function of PrPC, we investigated whether Prnp knockout mice(Prnp0/0)display age-dependent behavioral abnormalities. Matched sets of Prnp0/0 ...

  19. Age-dependent dichotomous effect of superoxide dismutase Ala16Val polymorphism on oxidized LDL levels

    PubMed Central

    Kanoni, Stavroula; Panagiotakos, Demosthenes B.; Louizou, Eirini; Grigoriou, Efi; Chrysohoou, Christina; Pitsavos, Christos; Stefanadis, Christodoulos

    2008-01-01

    We investigated the association between superoxide dismutase (SOD) Ala16Val polymorphism and the levels of oxidized LDL lipoprotein-C (ox-LDL-C) in two age-different Greek cohorts. Four hundred fifteen middle-aged (n = 147 females: 43.2 ± 13 years, n = 268 males: 43.3 ± 14 years) Caucasian Greek subjects consisted the middle aged cohort. One hundred seventy five elderly (n = 88 females: 79.9 ± 4 years; n = 87 males: 80.6 ± 4 years) were selected from the elderly cohort. Genotype data were obtained for all of them. Multiple linear regression analysis, stratified by gender and adjusted for age, smoking habits and body mass index as covariates, showed higher ox-LDL-C levels for the middle aged men with the Val/Val genotype, compared to the other allele (Ala/Ala and Ala/Val) carriers (65.9 ± 25.7 vs. 55.7 ± 20.5 mg/dl; standardized β coefficient = 0.192, P = 0.012). On the contrary, elderly women with the Val/Val genotype occurred with lower ox-LDL-C levels compared to the Ala/Ala or Ala/Val genotype (74.2 ± 22.1 vs. 86.5 ± 26.6 mg/dl; standardized β coefficient = -0.269, P = 0.015). The same trend was also recorded in elderly men, however without reaching statistical significance (standardized β coefficient = -0.187, P = 0.077). Moreover, elderly men and women with the Ala/Ala or Ala/Val genotype presented higher triglycerides levels compared to Val/Val (women: 145.2 ± 68.7 vs. 114.3 ± 34.3 mg/dl, P = 0.027; men: 147.8 ± 72.4 vs. 103.7 ± 38.0 mg/dl, P = 0.002). Additionally, middle aged men with the Val/Val genotype had higher HDL-C levels compared to the Ala allele carriers. The results suggest that SOD Ala16Val polymorphism is an age-dependent modulator of ox-LDL-C levels in middle-aged men and elderly women. PMID:18305395

  20. Enteric fever in a British soldier from Sierra Leone.

    PubMed

    Osborne, Lucy G; Brown, M; Bailey, M S

    2016-06-01

    Enteric fever (typhoid and paratyphoid) remains a threat to British troops overseas and causes significant morbidity and mortality. We report the case of a soldier who developed typhoid despite appropriate vaccination and field hygiene measures, which began 23 days after returning from a deployment in Sierra Leone. The incubation period was longer than average, symptoms started 2 days after stopping doxycycline for malaria chemoprophylaxis and initial blood cultures were negative. The Salmonella enterica serovar Typhi eventually isolated was resistant to amoxicillin, co-amoxiclav, co-trimoxazole and nalidixic acid and had reduced susceptibility to ciprofloxacin. He was successfully treated with ceftriaxone followed by azithromycin, but 1 month later he remained fatigued and unable to work. The clinical and laboratory features of enteric fever are non-specific and the diagnosis should be considered in troops returning from an endemic area with a febrile illness. Multiple blood cultures and referral to a specialist unit may be required. PMID:26243802

  1. Leon Cooper's Perspective on Teaching Science: An Interview Study

    NASA Astrophysics Data System (ADS)

    Niaz, Mansoor; Klassen, Stephen; McMillan, Barbara; Metz, Don

    2010-01-01

    The authors of this paper portray the perspective of Professor Leon Cooper, a theoretical physicist, Nobel laureate, active researcher, and physics textbook author, on teaching science and on the nature of science (NOS). The views presented emerged from an interview prepared by the authors and responded to in writing by Professor Cooper. Based on the gathered data and the subsequent interpretation of it, the authors identified several educational implications and drew the following conclusions: (a) science should be taught within an historical perspective; (b) textbook authors generally have an empiricist epistemology which makes their presentation of science difficult to understand; (c) an historical perspective inevitably involves comparing, contrasting, and scrutinizing different historical accounts of the same events; (d) varying interpretations of observations do not undermine the objective nature of science; (e) new ideas in physics comprise an imposed vision of the world, and these ideas are then slowly accepted by the scientific community; (f) the current view in any science is almost always a mixture of data, hypotheses, theoretical ideas, and conjectures; (g) since experiments are difficult to perform and understand, scientists rely on their presuppositions to guide the integration of data, theory, and conjectures; (h) inconsistencies in the construction of theories can facilitate new theoretical ideas; and (i) case studies based on various experiments show that scientists use intuition which is guided by facts, conjectures, and speculations.

  2. Leon Van Speybroeck Wins Astrophysics Bruno Rossi Prize

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Leon Van Speybroeck of the Harvard-Smithsonian Center for Astrophysics in Cambridge Massachusetts was awarded the 2002 Bruno Rossi Prize of the High-Energy Astrophysics Division of the American Astronomy Society. The Rossi Prize is an arnual recognition of significant contributions in high-energy astrophysics in honor of the Massachusetts Institute of Technology's late Professor Bruno Rossi, an authority on cosmic ray physics and a pioneer in the field of x-ray astronomy. Van Speybroeck, who led the effort to design and make the x-ray mirrors for NASA's premier Chandra X-Ray Observatory, was recognized for a career of stellar achievements in designing precision x-ray optics. As Telescope Scientist for Chandra, he has worked for more than 20 years with a team that includes scientists and engineers from the Harvard-Smithsonian, NASA's Marshall Space Flight Center, TRW, Inc., Huhes-Danbury (now B.F. Goodrich Aerospace), Optical Coating Laboratories, Inc., and Eastman-Kodak on all aspects of the x-ray mirror assembly that is the heart of the observatory.

  3. Electrocardiographic parameters in the clinically healthy Zamorano-leones donkey.

    PubMed

    Escudero, Andrés; González, José R; Benedito, José L; Prieto, Felipe R; Ayala, Ignacio

    2009-12-01

    Limited information exists regarding electrocardiographic parameters in clinically healthy donkeys. The study was carried out in 75 healthy adult animals (40 females and 35 males) using the Einthoven standard II and base-apex leads. The P wave showed usually a bifid shape deflection. The QRS complex of the donkeys appeared in several forms: QR and R were the most frequent in limb lead II, and QS and QR in the base-apex lead. Most T waves presented a simple negative configuration in lead II and biphasic shape in the base-apex one. Mean heart rate value was 52 beats per minute. The direction of the QRS vector in lead II had a mean value of 91.4 degrees. We observed a lack of detected arrhythmias. Statistically significant differences were observed between sexes for several parameters. The electrocardiogram of Zamorano-leones donkey differs in several duration, amplitude and morphologic parameters from that of several breeds of horses and donkeys. This fact justifies obtaining values for a specific breed against which to compare values for the same breed. PMID:19433331

  4. AAS Publishing News: An Interview with Leon Golub

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    In the lead-up to next weeks 2016 Solar Physics Division (SPD) meeting, we wanted to introduce you to Leon Golub, our new Lead Editor for the Sun and the Heliosphere corridor.Leon is a Senior Astrophysicist in the High Energy Division at the Harvard-Smithsonian Center for Astrophysics. He specializes in studies of solar and stellar magnetic activity, and he has built numerous rocket and satellite instruments to study the Sun and its dynamic behavior.* * * * *Tell me about your field of research and some of your current projects.Ive been working primarily on understanding the dynamics of the solar corona, especially using new types of instrumentation that can provide challenges to our theoretical understanding.Image of the Apollo Telescope Mount on Skylab. [NASA]Why did you choose this field?Shortly after graduating from MIT in experimental high energy physics I found a position with a group that was preparing to launch an X-ray telescope on Skylab as part of the cluster of solar instruments called the Apollo Telescope Mount. I have stayed with that field and related ones ever since.What do you consider to be some of the biggest open questions in solar and heliospheric research today?There are so many major questions that its difficult to just settle on a few. The heliosphere is defined by the extent of the influence of the Sun on the interstellar medium. It is an exciting time in that area of study, because we now have the ability to make impressive new observations that allow us to test our understanding of that outer boundary.Within those limits, the Sun has a major influence on solar system objects via its gravitational pull, its light and heat, and the magnetized plasma and high energy particles that it emits in all directions. We are making major discoveries related to how the Sun has influenced the formation and evolution of the planets, including our own planet.The source of all this influence is, of course, the Sun itself, and we are working to understand

  5. Mating patterns of female Leon Springs pupfish Cyprinodon bovinus.

    PubMed

    Leiser, J K; Gagliardi-Seeley, J L; Wisenden, B D; Itzkowitz, M

    2015-09-01

    In a field study of Leon Springs pupfish Cyprinodon bovinus, two questions about female promiscuity were investigated. First, were females selective in the males with whom they spawned or were they unselective, spawning randomly among males? Second, how promiscuous were the females, i.e. with how many males did they spawn? If simply spawning with many males maximized a female's reproductive success, then females might be expected to spawn randomly with as many males as possible. Alternatively, if females were selective but engaged in multiple mating, they would limit their spawning to preferred males. In the only wild population of this endangered fish, breeding males defend closely associated territories in the shallow margins of a single desert pool. No territories were observed elsewhere in the pool. Therefore, all territorial males were present simultaneously and females could survey all of them, depositing any number of eggs with one, a few or many males. Rather than spawning randomly, females surveyed many males first, visited relatively few males and ultimately spawned with a small fraction of those available males. With increasing numbers of spawns, however, females increased the number of different mates with whom they spawned. Thus, females showed a bet-hedging tactic of having a narrow mate preference while also laying eggs in the territories of other males, possibly to reduce egg predation and to avoid inbreeding. PMID:26289774

  6. Human dopamine transporter gene: differential regulation of 18-kb haplotypes

    PubMed Central

    Zhao, Ying; Xiong, Nian; Liu, Yang; Zhou, Yanhong; Li, Nuomin; Qing, Hong; Lin, Zhicheng

    2013-01-01

    Aim Since previous functional studies of short haplotypes and polymorphic sites of SLC6A3 have shown variant-dependent and drug-sensitive promoter activity, this study aimed to understand whether a large SLC6A3 regulatory region, containing these small haplotypes and polymorphic sites, can display haplotype-dependent promoter activity in a drug-sensitive and pathway-related manner. Materials & methods By creating and using a single copy number luciferase-reporter vector, we examined regulation of two different SLC6A3 haplotypes (A and B) of the 5′ 18-kb promoter and two known downstream regulatory variable number tandem repeats by 17 drugs in four different cellular models. Results The two regulatory haplotypes displayed up to 3.2-fold difference in promoter activity. The regulations were drug selective (37.5% of the drugs showed effects), and both haplotype and cell type dependent. Pathway analysis revealed at least 13 main signaling hubs targeting SLC6A3, including histone deacetylation, AKT, PKC and CK2 α-chains. Conclusion SLC6A3 may be regulated via either its promoter or the variable number tandem repeats independently by specific signaling pathways and in a haplotype-dependent manner. Furthermore, we have developed the first pathway map for SLC6A3 regulation. These findings provide a framework for understanding complex and variant-dependent regulations of SLC6A3. PMID:24024899

  7. A spatial haplotype copying model with applications to genotype imputation.

    PubMed

    Yang, Wen-Yun; Hormozdiari, Farhad; Eskin, Eleazar; Pasaniuc, Bogdan

    2015-05-01

    Ever since its introduction, the haplotype copy model has proven to be one of the most successful approaches for modeling genetic variation in human populations, with applications ranging from ancestry inference to genotype phasing and imputation. Motivated by coalescent theory, this approach assumes that any chromosome (haplotype) can be modeled as a mosaic of segments copied from a set of chromosomes sampled from the same population. At the core of the model is the assumption that any chromosome from the sample is equally likely to contribute a priori to the copying process. Motivated by recent works that model genetic variation in a geographic continuum, we propose a new spatial-aware haplotype copy model that jointly models geography and the haplotype copying process. We extend hidden Markov models of haplotype diversity such that at any given location, haplotypes that are closest in the genetic-geographic continuum map are a priori more likely to contribute to the copying process than distant ones. Through simulations starting from the 1000 Genomes data, we show that our model achieves superior accuracy in genotype imputation over the standard spatial-unaware haplotype copy model. In addition, we show the utility of our model in selecting a small personalized reference panel for imputation that leads to both improved accuracy as well as to a lower computational runtime than the standard approach. Finally, we show our proposed model can be used to localize individuals on the genetic-geographical map on the basis of their genotype data. PMID:25526526

  8. General Framework for Meta‐Analysis of Haplotype Association Tests

    PubMed Central

    Wang, Shuai; Zhao, Jing Hua; An, Ping; Guo, Xiuqing; Jensen, Richard A.; Marten, Jonathan; Huffman, Jennifer E.; Meidtner, Karina; Boeing, Heiner; Campbell, Archie; Rice, Kenneth M.; Scott, Robert A.; Yao, Jie; Schulze, Matthias B.; Wareham, Nicholas J.; Borecki, Ingrid B.; Province, Michael A.; Rotter, Jerome I.; Hayward, Caroline; Goodarzi, Mark O.; Meigs, James B.

    2016-01-01

    ABSTRACT For complex traits, most associated single nucleotide variants (SNV) discovered to date have a small effect, and detection of association is only possible with large sample sizes. Because of patient confidentiality concerns, it is often not possible to pool genetic data from multiple cohorts, and meta‐analysis has emerged as the method of choice to combine results from multiple studies. Many meta‐analysis methods are available for single SNV analyses. As new approaches allow the capture of low frequency and rare genetic variation, it is of interest to jointly consider multiple variants to improve power. However, for the analysis of haplotypes formed by multiple SNVs, meta‐analysis remains a challenge, because different haplotypes may be observed across studies. We propose a two‐stage meta‐analysis approach to combine haplotype analysis results. In the first stage, each cohort estimate haplotype effect sizes in a regression framework, accounting for relatedness among observations if appropriate. For the second stage, we use a multivariate generalized least square meta‐analysis approach to combine haplotype effect estimates from multiple cohorts. Haplotype‐specific association tests and a global test of independence between haplotypes and traits are obtained within our framework. We demonstrate through simulation studies that we control the type‐I error rate, and our approach is more powerful than inverse variance weighted meta‐analysis of single SNV analysis when haplotype effects are present. We replicate a published haplotype association between fasting glucose‐associated locus (G6PC2) and fasting glucose in seven studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and we provide more precise haplotype effect estimates. PMID:27027517

  9. "Extended" A1, B8, DR3 haplotype shows remarkable linkage disequilibrium but is similar to nonextended haplotypes in terms of diabetes risk.

    PubMed

    Ide, Akane; Babu, Sunanda R; Robles, David T; Wang, Tianbao; Erlich, Henry A; Bugawan, Teodorica L; Rewers, Marian; Fain, Pamela R; Eisenbarth, George S

    2005-06-01

    To evaluate potential differential diabetes risk of DR3 haplotypes we have evaluated class I alleles as well as two microsatellites previously associated with differential risk associated with DR3 haplotypes. We found that over one-third of patient DR3 chromosomes consisted of an extended DR3 haplotype, from DQ2 to D6S2223 (DQ2, DR3, D6S273-143, MIC-A5.1, HLA-B8, HLA-Cw7, HLA-A1, and D6S2223-177) with an identical extended haplotype in controls. The extended haplotype was present more frequently (35.1% of autoimmune-associated DR3 haplotypes, 39.4% of control DR3 haplotypes) than other haplotypes (no other haplotype >5% of DR3 haplotypes) and remarkably conserved, but it was not transmitted from parents to affected children more frequently than nonconserved DR3-bearing haplotypes. This suggests that if all alleles are truly identical for the major A1, B8, DR3 haplotype (between A1 and DR3), with different alleles on nonconserved haplotypes without differential diabetes risk, then in this region of the genome DR3-DQ2 may be the primary polymorphisms of common haplotypes contributing to diabetes risk. PMID:15919812

  10. Molecular Characterization of the First Ebola Virus Isolated in Italy, from a Health Care Worker Repatriated from Sierra Leone

    PubMed Central

    Castilletti, Concetta; Carletti, Fabrizio; Gruber, Cesare E. M.; Bordi, Licia; Lalle, Eleonora; Quartu, Serena; Meschi, Silvia; Lapa, Daniele; Colavita, Francesca; Chiappini, Roberta; Mazzarelli, Antonio; Marsella, Patrizia; Petrosillo, Nicola; Nicastri, Emanuele; Chillemi, Giovanni; Valentini, Alessio; Desideri, Alessandro; Di Caro, Antonino; Ippolito, Giuseppe

    2015-01-01

    Here, we report the complete genome sequence of an Ebola virus (EBOV) isolated from a health worker repatriated from Sierra Leone to Italy in November 2014. The sequence, clustering in clade 3 of the Sierra Leone sequences, was analyzed with respect to mutations possibly affecting diagnostic and therapeutic targets as well as virulence. PMID:26089420

  11. The Effect of Single-Nucleotide Polymorphism Marker Selection on Patterns of Haplotype Blocks and Haplotype Frequency Estimates

    PubMed Central

    Nothnagel, Michael; Rohde, Klaus

    2005-01-01

    The definition of haplotype blocks of single-nucleotide polymorphisms (SNPs) has been proposed so that the haplotypes can be used as markers in association studies and to efficiently describe human genetic variation. The International Haplotype Map (HapMap) project to construct a comprehensive catalog of haplotypic variation in humans is underway. However, a number of factors have already been shown to influence the definition of blocks, including the population studied and the sample SNP density. Here, we examine the effect that marker selection has on the definition of blocks and the pattern of haplotypes by using comparable but complementary SNP sets and a number of block definition methods in various genomic regions and populations that were provided by the Encyclopedia of DNA Elements (ENCODE) project. We find that the chosen SNP set has a profound effect on the block-covered sequence and block borders, even at high marker densities. Our results question the very concept of discrete haplotype blocks and the possibility of generalizing block findings from the HapMap project. We comparatively apply the block-free tagging-SNP approach and discuss both the haplotype approach and the tagging-SNP approach as means to efficiently catalog genetic variation. PMID:16380910

  12. Evaluation of the Leon3 soft-core processor within a Xilinx radiation-hardened field-programmable gate array.

    SciTech Connect

    Learn, Mark Walter

    2012-01-01

    The purpose of this document is to summarize the work done to evaluate the performance of the Leon3 soft-core processor in a radiation environment while instantiated in a radiation-hardened static random-access memory based field-programmable gate array. This evaluation will look at the differences between two soft-core processors: the open-source Leon3 core and the fault-tolerant Leon3 core. Radiation testing of these two cores was conducted at the Texas A&M University Cyclotron facility and Lawrence Berkeley National Laboratory. The results of these tests are included within the report along with designs intended to improve the mitigation of the open-source Leon3. The test setup used for evaluating both versions of the Leon3 is also included within this document.

  13. The senescence-accelerated mouse (SAM): a higher oxidative stress and age-dependent degenerative diseases model.

    PubMed

    Chiba, Yoichi; Shimada, Atsuyoshi; Kumagai, Naoko; Yoshikawa, Keisuke; Ishii, Sanae; Furukawa, Ayako; Takei, Shiro; Sakura, Masaaki; Kawamura, Noriko; Hosokawa, Masanori

    2009-04-01

    The SAM strain of mice is actually a group of related inbred strains consisting of a series of SAMP (accelerated senescence-prone) and SAMR (accelerated senescence-resistant) strains. Compared with the SAMR strains, the SAMP strains show a more accelerated senescence process, a shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to human geriatric disorders. The higher oxidative stress status observed in SAMP mice is partly caused by mitochondrial dysfunction, and may be a cause of this senescence acceleration and age-dependent alterations in cell structure and function. Based on our recent observations, we discuss a possible mechanism for mitochondrial dysfunction resulting in the excessive production of reactive oxygen species, and a role for the hyperoxidative stress status in neurodegeneration in SAMP mice. These SAM strains can serve as a useful tool to understand the cellular mechanisms of age-dependent degeneration, and to develop clinical interventions. PMID:18688709

  14. Mitochondrial haplotype analysis for differentiation of isolates of Phytophthora cinnamomi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While Phytophthora cinnamomi is heterothallic, there are few instances of successful crossing in laboratory experiments and analysis of field populations indicates a clonally reproducing population. In the absence of sexual recombination the ability to monitor mitochondrial haplotypes may provide a...

  15. Y-chromosome STR haplotypes in males from Greenland.

    PubMed

    Hallenberg, Charlotte; Tomas, Carmen; Simonsen, Bo; Morling, Niels

    2009-09-01

    A total of 272 males from Greenland were typed for 11 Y-chromosome STRs DYS19, DYS385a/b, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439 with the PowerPlex Y System (Promega). A total of 146 different haplotypes were observed and the haplotype diversity was 0.9887. The number of haplotypes seen once was 108 and the most common haplotype was observed in 12 males. A significant F(ST) value was observed (F(ST)=0.012, P<0.00001) when comparing the population of 15 locations in Greenland assigned to 7 groups. The significance could mainly be attributed to the subpopulation of males from Tasiilaq (East of Greenland). The R(ST) value was not statistically significant (R(ST)=0.016, P=0.15). PMID:19647703

  16. Association of a bovine prion gene haplotype with atypical BSE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Atypical bovine spongiform encephalopathies (BSEs) are recently recognized prion diseases of cattle. Atypical BSEs are rare; approximately 30 cases have been identified worldwide. We tested prion gene (PRNP) haplotypes for an association with atypical BSE. Methodology/Principal Findin...

  17. De novo assembly of a haplotype-resolved human genome.

    PubMed

    Cao, Hongzhi; Wu, Honglong; Luo, Ruibang; Huang, Shujia; Sun, Yuhui; Tong, Xin; Xie, Yinlong; Liu, Binghang; Yang, Hailong; Zheng, Hancheng; Li, Jian; Li, Bo; Wang, Yu; Yang, Fang; Sun, Peng; Liu, Siyang; Gao, Peng; Huang, Haodong; Sun, Jing; Chen, Dan; He, Guangzhu; Huang, Weihua; Huang, Zheng; Li, Yue; Tellier, Laurent C A M; Liu, Xiao; Feng, Qiang; Xu, Xun; Zhang, Xiuqing; Bolund, Lars; Krogh, Anders; Kristiansen, Karsten; Drmanac, Radoje; Drmanac, Snezana; Nielsen, Rasmus; Li, Songgang; Wang, Jian; Yang, Huanming; Li, Yingrui; Wong, Gane Ka-Shu; Wang, Jun

    2015-06-01

    The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-genome shotgun strategies, based solely on next-generation sequencing and hierarchical assembly methods. We applied our sequencing method to the genome of an Asian individual and generated a 5.15-Gb assembled genome with a haplotype N50 of 484 kb. Our analysis identified previously undetected indels and 7.49 Mb of novel coding sequences that could not be aligned to the human reference genome, which include at least six predicted genes. This haplotype-resolved genome represents the most complete de novo human genome assembly to date. Application of our approach to identify individual haplotype differences should aid in translating genotypes to phenotypes for the development of personalized medicine. PMID:26006006

  18. Haplotype hitchhiking promotes trait coselection in Brassica napus.

    PubMed

    Qian, Lunwen; Qian, Wei; Snowdon, Rod J

    2016-07-01

    Local haplotype patterns surrounding densely spaced DNA markers with significant trait associations can reveal information on selective sweeps and genome diversity associated with important crop traits. Relationships between haplotype and phenotype diversity, coupled with analysis of gene content in conserved haplotype blocks, can provide insight into coselection for nonrelated traits. We performed genome-wide analysis of haplotypes associated with the important physiological and agronomic traits leaf chlorophyll and seed glucosinolate content, respectively, in the major oilseed crop species Brassica napus. A locus on chromosome A01 showed opposite effects on leaf chlorophyll content and seed glucosinolate content, attributed to strong linkage disequilibrium (LD) between orthologues of the chlorophyll biosynthesis genes EARLY LIGHT-INDUCED PROTEIN and CHLOROPHYLL SYNTHASE, and the glucosinolate synthesis gene ATP SULFURYLASE 1. Another conserved haplotype block, on chromosome A02, contained a number of chlorophyll-related genes in LD with orthologues of the key glucosinolate biosynthesis genes METHYLTHIOALKYMALATE SYNTHASE-LIKE 1 and 3. Multigene haplogroups were found to have a significantly greater contribution to variation for chlorophyll content than haplotypes for any single gene, suggesting positive effects of additive locus accumulation. Detailed reanalysis of population substructure revealed a clade of ten related accessions exhibiting high leaf chlorophyll and low seed glucosinolate content. These accessions each carried one of the above-mentioned haplotypes from A01 or A02, generally in combination with further chlorophyll-associated haplotypes from chromosomes A05 and/or C05. The phenotypic rather than pleiotropic correlations between leaf chlorophyll content index and seed GSL suggest that LD may have led to inadvertent coselection for these two traits. PMID:26800855

  19. Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development

    PubMed Central

    Beheshti, Afshin; Wage, Justin; McDonald, J. Tyson; Lamont, Clare; Peluso, Michael; Hahnfeldt, Philip; Hlatky, Lynn

    2015-01-01

    The concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3ε, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease. PMID:26497558

  20. Microsurgeons do better--tactile training might prevent the age-dependent decline of the sensibility of the hand.

    PubMed

    Schmauss, Daniel; Megerle, Kai; Weinzierl, Andrea; Agua, Kariem; Cerny, Michael; Schmauss, Verena; Lohmeyer, Joern A; Machens, Hans-Guenther; Erne, Holger

    2015-12-01

    Recent data demonstrate that the normal sensibility of the hand seems to be age-dependent with the best values in the third decade and a consecutive deterioration afterwards. However, it is not clear if long-term tactile training might prevent this age-dependent decline. We evaluated sensibility of the hand in 125 surgeons aged between 26 and 75 years who perform microsurgical operations, thereby undergoing regular tactile training. We examined sensibility of the radial digital nerve of the index finger (N3) and the ulnar digital nerve of the small finger (N10) using static and moving two-point discrimination (2PD) tests and compared the results to 154 age-matched individuals without specific long-term tactile training. We found significantly lower static and moving 2PD values for the sixth, seventh, and eighth decade of life in the microsurgery group compared to the control group (p < 0.05). This study demonstrates that long-term tactile training might prevent the known age-dependent decline of the sensibility of the hand. PMID:26306813

  1. MHC Class II haplotypes of Colombian Amerindian tribes

    PubMed Central

    Yunis, Juan J.; Yunis, Edmond J.; Yunis, Emilio

    2013-01-01

    We analyzed 1041 individuals belonging to 17 Amerindian tribes of Colombia, Chimila, Bari and Tunebo (Chibcha linguistic family), Embera, Waunana (Choco linguistic family), Puinave and Nukak (Maku-Puinave linguistic families), Cubeo, Guanano, Tucano, Desano and Piratapuyo (Tukano linguistic family), Guahibo and Guayabero (Guayabero Linguistic Family), Curripaco and Piapoco (Arawak linguistic family) and Yucpa (Karib linguistic family). for MHC class II haplotypes (HLA-DRB1, DQA1, DQB1). Approximately 90% of the MHC class II haplotypes found among these tribes are haplotypes frequently encountered in other Amerindian tribes. Nonetheless, striking differences were observed among Chibcha and non-Chibcha speaking tribes. The DRB1*04:04, DRB1*04:11, DRB1*09:01 carrying haplotypes were frequently found among non-Chibcha speaking tribes, while the DRB1*04:07 haplotype showed significant frequencies among Chibcha speaking tribes, and only marginal frequencies among non-Chibcha speaking tribes. Our results suggest that the differences in MHC class II haplotype frequency found among Chibcha and non-Chibcha speaking tribes could be due to genetic differentiation in Mesoamerica of the ancestral Amerindian population into Chibcha and non-Chibcha speaking populations before they entered into South America. PMID:23885196

  2. [Analysis of mitochondrial DNA haplotypes in yakut population].

    PubMed

    Fedorova, S A; Bermisheva, M A; Villems, R; Maksimova, N R; Khusnutdinova, E K

    2003-01-01

    To study the mitochondrial gene pool structure in Yakuts, polymorphism of mtDNA hypervariable segment I (16,024-16,390) was analyzed in 191 people sampled from the indigenous population of the Sakha Republic. In total, 67 haplotypes of 14 haplogroups were detected. Most (91.6%) haplotypes belonged to haplogroups A, B, C, D, F, G, M*, and Y, which are specific for East Eurasian ethnic groups; 8.4% haplotypes represented Caucasian haplogroups H, HV1, J, T, U, and W. A high frequency of mtDNA types belonging to Asian supercluster M was peculiar for Yakuts: mtDNA types belonging to haplogroup C, D, or G and undifferentiated mtDNA types of haplogroup M (M*) accounted for 81% of all haplotypes. The highest diversity was observed for haplogroups C and D, which comprised respectively 22 (44%) and 18 (30%) haplotypes. Yakuts showed the lowest genetic diversity (H = 0.964) among all Turkic ethnic groups. Phylogenetic analysis testified to a common genetic substrate of Yakuts, Mongols, and Central Asian (Kazakh, Kyrgyz, Uigur) populations. Yakuts proved to share 21 (55.5%) mtDNA haplogroups with the Central Asian ethnic groups and Mongols. Comparisons with modern paleo-Asian populations (Chukcha, Itelmen, Koryaks) revealed three (8.9%) haplotypes common for Yakuts and Koryaks. The results of mtDNA analysis disagree with the hypothesis of an appreciable paleo-Asian contribution to the modern Yakut gene pool. PMID:12942638

  3. Haplotype Reconstruction in Large Pedigrees with Many Untyped Individuals

    NASA Astrophysics Data System (ADS)

    Li, Xin; Li, Jing

    Haplotypes, as they specify the linkage patterns between dispersed genetic variations, provide important information for understanding the genetics of human traits. However haplotypes are not directly available from current genotyping platforms, and hence there are extensive investigations of computational methods to recover such information. Two major computational challenges arising in current family-based disease studies are large family sizes and many ungenotyped family members. Traditional haplotyping methods can neither handle large families nor families with missing members. In this paper, we propose a method which addresses these issues by integrating multiple novel techniques. The method consists of three major components: pairwise identical-bydescent (IBD) inference, global IBD reconstruction and haplotype restoring. By reconstructing the global IBD of a family from pairwise IBD and then restoring the haplotypes based on the inferred IBD, this method can scale to large pedigrees, and more importantly it can handle families with missing members. Compared with existing methods, this method demonstrates much higher power to recover haplotype information, especially in families with many untyped individuals.

  4. Polymorphic DNA haplotypes at the LDL receptor locus.

    PubMed Central

    Leitersdorf, E; Chakravarti, A; Hobbs, H H

    1989-01-01

    Mutations in the low-density lipoprotein (LDL) receptor gene result in the autosomal dominant disorder familial hypercholesterolemia (FH). Many different LDL receptor mutations have been identified and characterized, demonstrating a high degree of allelic heterogeneity at this locus. The ability to identify mutant LDL receptor genes for prenatal diagnosis of homozygous FH or to study the role of the LDL receptor gene in polygenic hypercholesterolemia requires the use of closely linked RFLPs. In the present study we used 10 different RFLPs, including three newly described polymorphisms, to construct 123 independent haplotypes from 20 Caucasian American pedigrees. Our sample contained 31 different haplotypes varying in frequency from 0.8% to 29.3%; the five most common haplotypes account for 67.5% of the sample. The heterozygosity and PIC of each site were determined, and these values disclosed that eight of the RFLPs were substantially polymorphic. Linkage-disequilibrium analysis of the haplotype data revealed strong nonrandom associations among all 10 RFLPs, especially among those sites clustered in the 3' region of the gene. Evolutionary analysis suggests the occurrence of both mutational and recombinational events in the generation of the observed haplotypes. A strategy for haplotype analysis of the LDL receptor gene in individuals of Caucasian American descent is presented. Images Figure 2 Figure 3 PMID:2563635

  5. iXora: exact haplotype inferencing and trait association

    PubMed Central

    2013-01-01

    Background We address the task of extracting accurate haplotypes from genotype data of individuals of large F1 populations for mapping studies. While methods for inferring parental haplotype assignments on large F1 populations exist in theory, these approaches do not work in practice at high levels of accuracy. Results We have designed iXora (Identifying crossovers and recombining alleles), a robust method for extracting reliable haplotypes of a mapping population, as well as parental haplotypes, that runs in linear time. Each allele in the progeny is assigned not just to a parent, but more precisely to a haplotype inherited from the parent. iXora shows an improvement of at least 15% in accuracy over similar systems in literature. Furthermore, iXora provides an easy-to-use, comprehensive environment for association studies and hypothesis checking in populations of related individuals. Conclusions iXora provides detailed resolution in parental inheritance, along with the capability of handling very large populations, which allows for accurate haplotype extraction and trait association. iXora is available for non-commercial use from http://researcher.ibm.com/project/3430. PMID:23742238

  6. Association of a Bovine Prion Gene Haplotype with Atypical BSE

    PubMed Central

    Clawson, Michael L.; Richt, Juergen A.; Baron, Thierry; Biacabe, Anne-Gaëlle; Czub, Stefanie; Heaton, Michael P.; Smith, Timothy P. L.; Laegreid, William W.

    2008-01-01

    Background Atypical bovine spongiform encephalopathies (BSEs) are recently recognized prion diseases of cattle. Atypical BSEs are rare; approximately 30 cases have been identified worldwide. We tested prion gene (PRNP) haplotypes for an association with atypical BSE. Methodology/Principle Findings Haplotype tagging polymorphisms that characterize PRNP haplotypes from the promoter region through the three prime untranslated region of exon 3 (25.2 kb) were used to determine PRNP haplotypes of six available atypical BSE cases from Canada, France and the United States. One or two copies of a distinct PRNP haplotype were identified in five of the six cases (p = 1.3×10−4, two-tailed Fisher's exact test; CI95% 0.263–0.901, difference between proportions). The haplotype spans a portion of PRNP that includes part of intron 2, the entire coding region of exon 3 and part of the three prime untranslated region of exon 3 (13 kb). Conclusions/Significance This result suggests that a genetic determinant in or near PRNP may influence susceptibility of cattle to atypical BSE. PMID:18350166

  7. Evolution of haplotypes at the DRD2 locus

    SciTech Connect

    Castiglione, C.M.; Deinard, A.S.; Speed, W.C.

    1995-12-01

    We present here the first evolutionary perspective on haplotypes at DRD2, the locus for the dopamine D{sub 2} receptor. The dopamine D{sub 2} receptor plays a critical role in the functioning of many neural circuits in the human brain. If functionally relevant variation at the DRD2 locus exists, understanding the evolution of haplotypes on the basis of polymorphic sites encompassing the gene should provide a powerful framework for identifying that variation. Three DRD2 polymorphisms (TaqI {open_quotes}A{close_quotes} and {open_quotes}B{close_quotes} RFLPs and the (CA){sub n} short tandem repeat polymorphism) encompassing the coding sequences have been studied in 15 populations; these markers are polymorphic in all the populations studied, and they display strong and significant linkage disequilibria with each other. The common haplotypes for the two TaqI RFLPs are separately derived from the ancestral haplotype but predate the spread of modern humans around the world. The knowledge of how the various haplotypes have evolved, the allele frequencies of the haplotypes in human populations, and the physical relationships of the polymorphisms to each other and to the functional parts of the gene should now allow proper design and interpretation of association studies. 48 refs., 2 figs., 6 tabs.

  8. Whole-genome haplotyping by dilution, amplification, and sequencing

    PubMed Central

    Kaper, Fiona; Swamy, Sajani; Klotzle, Brandy; Munchel, Sarah; Cottrell, Joseph; Bibikova, Marina; Chuang, Han-Yu; Kruglyak, Semyon; Ronaghi, Mostafa; Eberle, Michael A.; Fan, Jian-Bing

    2013-01-01

    Standard whole-genome genotyping technologies are unable to determine haplotypes. Here we describe a method for rapid and cost-effective long-range haplotyping. Genomic DNA is diluted and distributed into multiple aliquots such that each aliquot receives a fraction of a haploid copy. The DNA template in each aliquot is amplified by multiple displacement amplification, converted into barcoded sequencing libraries using Nextera technology, and sequenced in multiplexed pools. To assess the performance of our method, we combined two male genomic DNA samples at equal ratios, resulting in a sample with diploid X chromosomes with known haplotypes. Pools of the multiplexed sequencing libraries were subjected to targeted pull-down of a 1-Mb contiguous region of the X-chromosome Duchenne muscular dystrophy gene. We were able to phase the Duchenne muscular dystrophy region into two contiguous haplotype blocks with a mean length of 494 kb. The haplotypes showed 99% agreement with the consensus base calls made by sequencing the individual DNAs. We subsequently used the strategy to haplotype two human genomes. Standard genomic sequencing to identify all heterozygous SNPs in the sample was combined with dilution-amplification–based sequencing data to resolve the phase of identified heterozygous SNPs. Using this procedure, we were able to phase >95% of the heterozygous SNPs from the diploid sequence data. The N50 for a Yoruba male DNA was 702 kb whereas the N50 for a European female DNA was 358 kb. Therefore, the strategy described here is suitable for haplotyping of a set of targeted regions as well as of the entire genome. PMID:23509297

  9. Whole-genome haplotyping by dilution, amplification, and sequencing.

    PubMed

    Kaper, Fiona; Swamy, Sajani; Klotzle, Brandy; Munchel, Sarah; Cottrell, Joseph; Bibikova, Marina; Chuang, Han-Yu; Kruglyak, Semyon; Ronaghi, Mostafa; Eberle, Michael A; Fan, Jian-Bing

    2013-04-01

    Standard whole-genome genotyping technologies are unable to determine haplotypes. Here we describe a method for rapid and cost-effective long-range haplotyping. Genomic DNA is diluted and distributed into multiple aliquots such that each aliquot receives a fraction of a haploid copy. The DNA template in each aliquot is amplified by multiple displacement amplification, converted into barcoded sequencing libraries using Nextera technology, and sequenced in multiplexed pools. To assess the performance of our method, we combined two male genomic DNA samples at equal ratios, resulting in a sample with diploid X chromosomes with known haplotypes. Pools of the multiplexed sequencing libraries were subjected to targeted pull-down of a 1-Mb contiguous region of the X-chromosome Duchenne muscular dystrophy gene. We were able to phase the Duchenne muscular dystrophy region into two contiguous haplotype blocks with a mean length of 494 kb. The haplotypes showed 99% agreement with the consensus base calls made by sequencing the individual DNAs. We subsequently used the strategy to haplotype two human genomes. Standard genomic sequencing to identify all heterozygous SNPs in the sample was combined with dilution-amplification-based sequencing data to resolve the phase of identified heterozygous SNPs. Using this procedure, we were able to phase >95% of the heterozygous SNPs from the diploid sequence data. The N50 for a Yoruba male DNA was 702 kb whereas the N50 for a European female DNA was 358 kb. Therefore, the strategy described here is suitable for haplotyping of a set of targeted regions as well as of the entire genome. PMID:23509297

  10. Croatian national reference Y-STR haplotype database.

    PubMed

    Mršić, Gordan; Gršković, Branka; Vrdoljak, Andro; Popović, Maja; Valpotić, Ivica; Anđelinović, Šimun; Stenzl, Vlastimil; Ehler, Edvard; Urban, Ludvik; Lacković, Gordana; Underhill, Peter; Primorac, Dragan

    2012-07-01

    A reference Y-chromosome short tandem repeat (STR) haplotype database is needed for Y-STR match interpretation as well as for national and regional characterization of populations. The aim of this study was to create a comprehensive Y-STR haplotype database of the Croatian contemporary population and to analyze substructure between the five Croatian regions. We carried out a statistical analysis of the data from previously performed genetic analyses collected during routine forensic work by the Forensic Science Centre "Ivan Vučetić". A total of 1,100 unrelated men from eastern, western, northern, southern and central Croatia were selected for the purpose of this study. Y-STRs were typed using the AmpFISTR Yfiler PCR amplification kit. Analysis of molecular variance calculated with the Y chromosome haplotype reference database online analysis tool included 16 population samples with 20,247 haplotypes. A total of 947 haplotypes were recorded, 848 of which were unique (89.5%). Haplotype diversity was 0.998, with the most frequent haplotype found in 9 of 1,100 men (0.82%). Locus diversity varied from 0.266 for DYS392 to 0.868 for DYS385. Discrimination capacity was 86.1%. Our results suggested high level of similarity among regional subpopulations within Croatia, except for mildly different southern Croatia. Relative resemblance was found with Bosnia and Herzegovina and Serbia. Whit Atheys' Haplogroup Predictor was used to estimate the frequencies of Y-chromosome haplogroups. I2a, R1a, E1b1b and R1b haplogroups were most frequent in all Croatian regions. These results are important in forensics and contribute to the population genetics and genetic background of the contemporary Croatian population. PMID:22391654

  11. Dimensional Anxiety Mediates Linkage of GABRA2 Haplotypes With Alcoholism

    PubMed Central

    Enoch, Mary-Anne; Schwartz, Lori; Albaugh, Bernard; Virkkunen, Matti; Goldman, David

    2015-01-01

    The GABAAα2 receptor gene (GABRA2) modulates anxiety and stress response. Three recent association studies implicate GABRA2 in alcoholism, however in these papers both common, opposite-configuration haplotypes in the region distal to intron3 predict risk. We have now replicated the GABRA2 association with alcoholism in 331 Plains Indian men and women and 461 Finnish Caucasian men. Using a dimensional measure of anxiety, harm avoidance (HA), we also found that the association with alcoholism is mediated, or moderated, by anxiety. Nine SNPs were genotyped revealing two haplotype blocks. Within the previously implicated block 2 region, we identified the two common, opposite-configuration risk haplotypes, A and B. Their frequencies differed markedly in Finns and Plains Indians. In both populations, most block 2 SNPs were significantly associated with alcoholism. The associations were due to increased frequencies of both homozygotes in alcoholics, indicating the possibility of alcoholic subtypes with opposite genotypes. Congruently, there was no significant haplotype association. Using HA as an indicator variable for anxiety, we found haplotype linkage to alcoholism with high and low dimensional anxiety, and to HA itself, in both populations. High HA alcoholics had the highest frequency of the more abundant haplotype (A in Finns, B in Plains Indians); low HA alcoholics had the highest frequency of the less abundant haplotype (B in Finns, A in Plains Indians) (Finns: P α0.007, OR α2.1, Plains Indians: P α0.040, OR α1.9). Non-alcoholics had intermediate frequencies. Our results suggest that within the distal GABRA2 region is a functional locus or loci that may differ between populations but that alters risk for alcoholism via the mediating action of anxiety. PMID:16874763

  12. Dimensional anxiety mediates linkage of GABRA2 haplotypes with alcoholism.

    PubMed

    Enoch, Mary-Anne; Schwartz, Lori; Albaugh, Bernard; Virkkunen, Matti; Goldman, David

    2006-09-01

    The GABAAalpha2 receptor gene (GABRA2) modulates anxiety and stress response. Three recent association studies implicate GABRA2 in alcoholism, however in these papers both common, opposite-configuration haplotypes in the region distal to intron3 predict risk. We have now replicated the GABRA2 association with alcoholism in 331 Plains Indian men and women and 461 Finnish Caucasian men. Using a dimensional measure of anxiety, harm avoidance (HA), we also found that the association with alcoholism is mediated, or moderated, by anxiety. Nine SNPs were genotyped revealing two haplotype blocks. Within the previously implicated block 2 region, we identified the two common, opposite-configuration risk haplotypes, A and B. Their frequencies differed markedly in Finns and Plains Indians. In both populations, most block 2 SNPs were significantly associated with alcoholism. The associations were due to increased frequencies of both homozygotes in alcoholics, indicating the possibility of alcoholic subtypes with opposite genotypes. Congruently, there was no significant haplotype association. Using HA as an indicator variable for anxiety, we found haplotype linkage to alcoholism with high and low dimensional anxiety, and to HA itself, in both populations. High HA alcoholics had the highest frequency of the more abundant haplotype (A in Finns, B in Plains Indians); low HA alcoholics had the highest frequency of the less abundant haplotype (B in Finns, A in Plains Indians) (Finns: P = 0.007, OR = 2.1, Plains Indians: P = 0.040, OR = 1.9). Non-alcoholics had intermediate frequencies. Our results suggest that within the distal GABRA2 region is a functional locus or loci that may differ between populations but that alters risk for alcoholism via the mediating action of anxiety. PMID:16874763

  13. Sierra Leone's Former Child Soldiers: A Follow-Up Study of Psychosocial Adjustment and Community Reintegration

    ERIC Educational Resources Information Center

    Betancourt, Theresa Stichick; Borisova, Ivelina Ivanova; Williams, Timothy Philip; Brennan, Robert T.; Whitfield, Theodore H.; de la Soudiere, Marie; Williamson, John; Gilman, Stephen E.

    2010-01-01

    This is the first prospective study to investigate psychosocial adjustment in male and female former child soldiers (ages 10-18; n = 156, 12% female). The study began in Sierra Leone in 2002 and was designed to examine both risk and protective factors in psychosocial adjustment. Over the 2-year period of follow-up, youth who had wounded or killed…

  14. "Farming Miners" or "Mining Farmers"?: Diamond Mining and Rural Development in Post-Conflict Sierra Leone

    ERIC Educational Resources Information Center

    Maconachie, Roy; Binns, Tony

    2007-01-01

    Sierra Leone is currently emerging from a brutal civil war that lasted most of the 1990s, and now has the dubious distinction of being ranked among the world's poorest countries. As thousands of displaced people move back to their villages, a large proportion of the predominantly farm-based rural population are growing food crops for the first…

  15. Assessment of the severity of Ebola virus disease in Sierra Leone in 2014-2015.

    PubMed

    Wong, J Y; Zhang, W; Kargbo, D; Haque, U; Hu, W; Wu, P; Kamara, A; Chen, Y; Kargbo, B; Glass, G E; Yang, R; Cowling, B J; Liu, C

    2016-05-01

    The current Ebola virus disease (EVD) epidemic in West Africa is unprecedented in scale, and Sierra Leone is the most severely affected country. The case fatality risk (CFR) and hospitalization fatality risk (HFR) were used to characterize the severity of infections in confirmed and probable EVD cases in Sierra Leone. Proportional hazards regression models were used to investigate factors associated with the risk of death in EVD cases. In total, there were 17 318 EVD cases reported in Sierra Leone from 23 May 2014 to 31 January 2015. Of the probable and confirmed EVD cases with a reported final outcome, a total of 2536 deaths and 886 recoveries were reported. CFR and HFR estimates were 74·2% [95% credibility interval (CrI) 72·6-75·5] and 68·9% (95% CrI 66·2-71·6), respectively. Risks of death were higher in the youngest (0-4 years) and oldest (⩾60 years) age groups, and in the calendar month of October 2014. Sex and occupational status did not significantly affect the mortality of EVD. The CFR and HFR estimates of EVD were very high in Sierra Leone. PMID:27029911

  16. Empowering Women through Education: Evidence from Sierra Leone. NBER Working Paper No. 18016

    ERIC Educational Resources Information Center

    Mocan, Naci H.; Cannonier, Colin

    2012-01-01

    We use data from Sierra Leone where a substantial education program provided increased access to education for primary-school age children but did not benefit children who were older. We exploit the variation in access to the program generated by date of birth and the variation in resources between various districts of the country. We find that…

  17. The Great War and Remembrance in Jose Leon Machado's "Memoria das Estrelas sem Brilho"

    ERIC Educational Resources Information Center

    Azevedo, Milton M.

    2011-01-01

    This article analyzes Jose Leon Machado's novel, "Memoria das Estrelas sem Brilho," as a multilayered historical novel in which a war story provides a background for comments on aspects of early twentieth-century Portuguese society, such as male bonding, religion, sexual mores, and social stratification. (Contains 11 notes.)

  18. Socio-Ecological Factors Affecting Pregnant Women's Anemia Status in Freetown, Sierra Leone

    ERIC Educational Resources Information Center

    M'Cormack, Fredanna; Drolet, Judy

    2012-01-01

    Background: Sierra Leone has high maternal mortality. Socio-ecological factors are considered contributing factors to this high mortality. Anemia is considered to be a direct cause of 4% of maternal deaths and an indirect cause of 20-40% of maternal deaths. Purpose: The current study explores socio-ecological contributing factors to the anemia…

  19. Training for Innovation: Capacity-Building in Agricultural Research in Post-War Sierra Leone

    ERIC Educational Resources Information Center

    Gboku, Matthew L. S.; Bebeley, Jenneh F.

    2016-01-01

    This paper examines how the Sierra Leone Agricultural Research Institute (SLARI) used training and development to build capacity for innovation in agricultural research following the country's civil war which ended in 2002. The Institute's training for innovation addressed different agricultural product value chains (APVCs) within the framework of…

  20. School Persistence in the Wake of War: Wartime Experiences, Reintegration Supports, and Dropout in Sierra Leone

    ERIC Educational Resources Information Center

    Zuilkowski, Stephanie Simmons; Betancourt, Theresa S.

    2014-01-01

    This article examines the relationship of wartime experience and reintegration supports to students' risk of school dropout. It draws on longitudinal, mixed-methods data collected among children and youth in Sierra Leone from 2002 through 2008. The study finds that family financial support and perceived social support are positively…

  1. Reconstruction versus Transformation: Post-War Education and the Struggle for Gender Equity in Sierra Leone

    ERIC Educational Resources Information Center

    Maclure, Richard; Denov, Myriam

    2009-01-01

    In post-war contexts, education is widely regarded as essential not only for civic reconciliation, but also as a key force for gender equity. In Sierra Leone, however, despite enhanced educational opportunities for girls, much of the emphasis on post-war educational reconstruction is unlikely to rectify gender inequities that remain entrenched…

  2. Linking Research, Extension and Farmers: The Case of Mangrove Swamp Rice Cultivation in Sierra Leone.

    ERIC Educational Resources Information Center

    Zinnah, Moses Moroe

    1994-01-01

    Interviews with 124 rice farmers in Sierra Leone revealed that farmers and extension staff have minimal participation and input in testing of new cultivation technologies. The top-down research approach has limited contact among researchers, extension staff, and farmers and affected the utility and application of research. (SK)

  3. Conservation Effects Assessment Project research in the Leon River and Riesel watersheds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2003, the Leon River basin was selected as a Benchmark watershed for the USDA Conservation Effects Project (CEAP) to complement the historical USDA-ARS experimental watersheds near Riesel, TX. In both watersheds the major water quality concerns are excessive nutrient and bacteria concentrations ...

  4. Educating Africans for Inferiority under British Rule: Bo School in Sierra Leone.

    ERIC Educational Resources Information Center

    Corby, Richard A.

    1990-01-01

    Sierra Leone's Bo School was established in 1906 by British colonial officials to educate chiefs' sons for subordinate positions. Nevertheless, the school contributed to creation of the postindependence ruling class. Enrollment, curriculum, student life, responsibilities of British and African teachers, and alumni networks are examined. Contains…

  5. Towards An Improved Curriculum for Agricultural Education at the Secondary School Level in Sierra Leone

    ERIC Educational Resources Information Center

    Conteh, Kaimasa M.

    1974-01-01

    Agricultural education is a recent addition to secondary curriculum in Sierra Leone. The author lists (1) justification for teaching it, (2) the Government's educational goals, (3) program planning steps needed, (4) tentative curriculum objectives, (5) central concepts to be transmitted to students, (6) guidelines on content organization, (7)…

  6. Bender-Gestalt Performance of Sierra Leone, West African Children from Four Sub-Cultures.

    ERIC Educational Resources Information Center

    Karr, Sharon K.

    1982-01-01

    The quality of the Bender-Gestalt performance of normal class-six children in four Sierra Leone subcultures with varying degrees of modernization showed the quality of the reproductions of the most modern subcultures to be significantly higher. The interaction of gender and the parallel to adult divisions of labor are discussed. (Author/CM)

  7. Rediscovering how Rural People Learn: An Initiative at the University of Sierra Leone.

    ERIC Educational Resources Information Center

    Haque, Farhana

    1987-01-01

    Reports on an on-going study of traditional education in Sierra Leone using examples of traditional crafts. Notes that traditional education is not cut off from life; involves the whole family; is practical and situational, interdisciplinary and multi-methodological; and is geared to the student's interests, talents, and learning patterns. (DHP)

  8. The Development of Education in Sierra Leone 1974/75-1975/76. Report (Part II).

    ERIC Educational Resources Information Center

    Ministry of Education (Sierra Leone).

    The report on educational development in Sierra Leone describes plans and policies set by the Ministry of Education to quicken the pace of social and economic development. In line with its objectives of eliminating illiteracy and providing primary education to every child of school age, the government has allocated a high proportion of the…

  9. Illiteracy, Colonial Legacy and Education: The Case of Modern Sierra Leone.

    ERIC Educational Resources Information Center

    Banya, Kingsley

    1993-01-01

    As a legacy of British colonial rule, Sierra Leone's education system gives half of its budget to higher education, heavily benefits the upper and middle classes and serves the poor and rural populations badly. The illiteracy rate is 85%. Policy recommendations are outlined for resource allocation and major restructuring of the education system.…

  10. Quality in an Integrated Rural Development Program: The Sierra Leone Experience.

    ERIC Educational Resources Information Center

    Banya, Kingsley

    1995-01-01

    A study investigated the quality of teaching in a rural development project in Sierra Leone, based on teacher knowledge of subject matter and beliefs about teaching and classroom management. Focus was on the preservice training of teachers and the attitudes they brought to teaching, rather than on classroom dynamics. Subjects were 100 teacher…

  11. Adult Learning Principles for the Improvement of Agricultural Extension in Sierra Leone.

    ERIC Educational Resources Information Center

    Ebun-Cole, W. A.

    1992-01-01

    Basic adult education principles should be applied in the change agent-farmer relationship in extension education in Sierra Leone. They include active learners, lifelong learning, teacher knowledge as nonabsolute, and the farming community as the center of problem generation. (SK)

  12. Youth Reintegration Training and Education for Peace (YRTEP) Program: Sierra Leone, 2000-2001. Impact Evaluation.

    ERIC Educational Resources Information Center

    Fauth, Gloria; Daniels, Bonnie

    Management Systems International (MSI), with funding from United States Agency for International Development Office of Transition Initiatives (USAID/OTI) and in coordination with other partners, is implementing a program in Sierra Leone entitled "Youth Reintegration Training and Education for Peace" (YRTEP). The object is to provide non-formal…

  13. Prevalence of Autism Spectrum Disorders in Guanajuato, Mexico: The Leon Survey

    ERIC Educational Resources Information Center

    Fombonne, Eric; Marcin, Carlos; Manero, Ana Cecilia; Bruno, Ruth; Diaz, Christian; Villalobos, Michele; Ramsay, Katrina; Nealy, Benjamin

    2016-01-01

    There are no epidemiological data on autism for Mexico. This study was conducted to generate a first estimate of ASD prevalence in Mexico. We surveyed children age eight in Leon (Guanajuato). The sample was stratified in two strata: (1) children having special education and medical records (SEMR; N = 432) and (2) children attending regular schools…

  14. The effects of epilepsy on child education in Sierra Leone.

    PubMed

    Ali, Desta B; Tomek, Michal; Lisk, Durodami R

    2014-08-01

    Epilepsy is associated with a significant burden of false beliefs and social stigma in the setting of Sub-Saharan Africa. To assess the impacts of epilepsy on child education in Sierra Leone (SL), we carried out a cross-sectional descriptive study examining its effects on school attendance, participation in physical activities, and social acceptance among classmates. We also assessed the knowledge, beliefs, and attitudes regarding epilepsy of both the children's caregivers and teachers. The data were collected at various epilepsy clinics and schools in Freetown, SL. A total of 50 patients were interviewed and questionnaires administered to their caregivers and teachers, making a total of 150 respondents. Fifty-one percent of the children were absent from school for >5 days per month. Ninety percent did not participate in games and sports, with the commonest reason being fear of occurrence of seizures. Thirty-six percent claimed having experienced negative attitude from their classmates. Regarding the caregivers, 48% believed that epilepsy was a medical illness, while 34% considered it a demonic manifestation. Forty-eight percent were apprehensive about sending their children to school, with 83% of these caregivers stating fear of seizures and potential injuries. Only 8% of the caregivers did not prevent their children from taking part in any physical activity at school. Regarding the teachers, 16% believed that epilepsy was a demonic manifestation, and 10% thought that it was contagious. Fourteen percent did not think that children with epilepsy should go to school, and 80% would prevent children with epilepsy from participating in games and sports. When faced with a child having a seizure, 48% would hold the child down, 12% would place a hard object in the child's mouth, and 12% would avoid any physical contact. In total, 20% of the children ceased attending school permanently; daily occurrence of seizures (p<0.05), negative attitude of classmates (p<0.001), and

  15. Fertility differentials in rural Sierra Leone: demographic and socioeconomic effects.

    PubMed

    Bailey, M; Serow, W J

    1991-01-01

    Multiple regression analysis with an ordinary least squares model was used to examine the demographic and socioeconomic determinants of fertility in rural Sierra Leone among a sample of 2000 women aged 15-49 years and 680 husbands in 1979. Size of place of current residence was of particular interest. The primary sampling unit (PSU) was proportionately sampled and systematically included chiefdoms for the Dasse, Kamajei, Kori, and Kowa in Moyamba District. Villages and towns were also sampled in the 3-stage probability sample. A wide selection of variables were collected; 11 variables were used in the analysis: children ever born as the dependent variable; husband's tribal affiliation, his religion, and size of place of current residence as background variables; educational levels of the respondent and her husband, reported annual household income, and wife's occupation; and age at marriage, infant and child mortality, and desired family size. The age structure was similar and small sample sizes for place limit the use of age grouping. Specification of each variable is given. The results reveal that in the full equation with all 11 variables, only size of place of residence is statistically significant (p = .10) and positively affecting fertility. Only opportunity cost to the wife (women working in nonagricultural jobs and educational attainment) negatively influences fertility as expected. Income effects are insignificant and in the wrong direction. Demographic influences are in the expected direction. In the analysis by size of place (small, 0-499; intermediate, 500-1999; and large, 2000), variance is demonstrated in the importance of explanatory variables. Background variables have coefficients hovering around 0. Opportunity cost (nonagricultural employment) is strong,and significantly negative only in large places. Household's infant and child mortality is significant and positive in all places. Desired family size is similar (positive and significant), but a

  16. Leaf age dependent changes in within-canopy variation in leaf functional traits: a meta-analysis.

    PubMed

    Niinemets, Ülo

    2016-05-01

    Within-canopy variation in leaf structural and photosynthetic characteristics is a major means by which whole canopy photosynthesis is maximized at given total canopy nitrogen. As key acclimatory modifications, leaf nitrogen content (N A) and photosynthetic capacity (A A) per unit area increase with increasing light availability in the canopy and these increases are associated with increases in leaf dry mass per unit area (M A) and/or nitrogen content per dry mass and/or allocation. However, leaf functional characteristics change with increasing leaf age during leaf development and aging, but the importance of these alterations for within-canopy trait gradients is unknown. I conducted a meta-analysis based on 71 canopies that were sampled at different time periods or, in evergreens, included measurements for different-aged leaves to understand how within-canopy variations in leaf traits (trait plasticity) depend on leaf age. The analysis demonstrated that in evergreen woody species, M A and N A plasticity decreased with increasing leaf age, but the change in A A plasticity was less suggesting a certain re-acclimation of A A to altered light. In deciduous woody species, M A and N A gradients in flush-type species increased during leaf development and were almost invariable through the rest of the season, while in continuously leaf-forming species, the trait gradients increased constantly with increasing leaf age. In forbs, N A plasticity increased, while in grasses, N A plasticity decreased with increasing leaf age, reflecting life form differences in age-dependent changes in light availability and in nitrogen resorption for growth of generative organs. Although more work is needed to improve the coverage of age-dependent plasticity changes in some plant life forms, I argue that the age-dependent variation in trait plasticity uncovered in this study is large enough to warrant incorporation in simulations of canopy photosynthesis through the growing period. PMID

  17. Predicting plasticity: acute context-dependent changes to vocal performance predict long-term age-dependent changes.

    PubMed

    James, Logan S; Sakata, Jon T

    2015-10-01

    Understanding the factors that predict and guide variation in behavioral change can lend insight into mechanisms of motor plasticity and individual differences in behavior. The performance of adult birdsong changes with age in a manner that is similar to rapid context-dependent changes to song. To reveal mechanisms of vocal plasticity, we analyzed the degree to which variation in the direction and magnitude of age-dependent changes to Bengalese finch song could be predicted by variation in context-dependent changes. Using a repeated-measures design, we found that variation in age-dependent changes to the timing, sequencing, and structure of vocal elements ("syllables") was significantly predicted by variation in context-dependent changes. In particular, the degree to which the duration of intersyllable gaps, syllable sequencing at branch points, and fundamental frequency of syllables within spontaneous [undirected (UD)] songs changed over time was correlated with the degree to which these features changed from UD song to female-directed (FD) song in young-adult finches (FDyoung). As such, the structure of some temporal features of UD songs converged over time onto the structure of FDyoung songs. This convergence suggested that the FDyoung song could serve as a stable target for vocal motor plasticity. Consequently, we analyzed the stability of FD song and found that the temporal structure of FD song changed significantly over time in a manner similar to UD song. Because FD song is considered a state of heightened performance, these data suggest that age-dependent changes could reflect practice-related improvements in vocal motor performance. PMID:26311186

  18. Accumulation of hyporesponsive, calcium extruding memory T cells as a key feature of age-dependent immune dysfunction.

    PubMed

    Miller, R A

    1991-03-01

    In this review I propose a hypothesis with a number of testable predictions: that the age-dependent decline in T lymphocyte function is largely the result of the accumulation of memory T lymphocytes with over-active plasma membrane calcium pumps. This idea is consistent with much, though not all, of the currently available data. I will start by presenting the evidence that suggested and most clearly supports this idea, then discuss apparently contrary data (some of it still difficult to reconcile with the model), and lastly consider the implications of the model for our understanding of late life development of the T cell immune system. PMID:2001603

  19. Mitochondrial Haplotype Influences Mycelial Growth of Agaricus bisporus Heterokaryons

    PubMed Central

    De La Bastide, P. Y.; Sonnenberg, A.; Van Griensven, L.; Anderson, J. B.; Horgen, P. A.

    1997-01-01

    We evaluated the influence of mitochondrial haplotype on growth of the common button mushroom Agaricus bisporus. Ten pairs of heterokaryon strains, each pair having the same nuclear genome but different mitochondrial genomes, were produced by controlled crosses among a group of homokaryons of both wild and commercial origins. Seven genetically distinct mitochondrial DNA (mtDNA) haplotypes were evaluated in different nuclear backgrounds. The growth of heterokaryon pairs differing only in their mtDNA haplotypes was compared by measuring mycelial radial growth rate on solid complete yeast medium (CYM) and compost extract medium and by measuring mycelial dry weight accumulation in liquid CYM. All A. bisporus strains were incubated at temperatures similar to those utilized in commercial production facilities (18, 22, and 26(deg)C). Statistically significant differences were detected in 8 of the 10 heterokaryon pairs evaluated for one or two of the three growth parameters measured. Some heterokaryon pairs showed differences in a single growth parameter at all three temperatures of incubation, suggesting a temperature-independent difference. Others showed differences at only a single temperature, suggesting a temperature-dependent difference. The influence of some mtDNA haplotypes on growth was dependent on the nuclear genetic background. Our results show that mtDNA haplotype can influence growth of A. bisporus heterokaryons in some nuclear backgrounds. These observations demonstrate the importance of including a number of mitochondrial genotypes and evaluating different nuclear-mitochondrial combinations of A. bisporus in strain improvement programs. PMID:16535683

  20. In Vivo Characterization of Human APOA5 Haplotypes

    SciTech Connect

    Ahituv, Nadav; Akiyama, Jennifer; Chapman-Helleboid, Audrey; Fruchart, Jamila; Pennacchio, Len A.

    2006-10-01

    Increased plasma triglycerides concentrations are an independent risk factor for cardiovascular disease. Numerous studies support a reproducible genetic association between two minor haplotypes in the human apolipoprotein A5 gene (APOA5) and increased plasma triglyceride concentrations. We thus sought to investigate the effect of these minor haplotypes (APOA5*2 and APOA5*3) on ApoAV plasma levels through the precise insertion of single-copy intact APOA5 haplotypes at a targeted location in the mouse genome. While we found no difference in the amount of human plasma ApoAV in mice containing the common APOA5*1 and minor APOA5*2 haplotype, the introduction of the single APOA5*3 defining allele (19W) resulted in 3-fold lower ApoAV plasma levels consistent with existing genetic association studies. These results indicate that S19W polymorphism is likely to be functional and explain the strong association of this variant with plasma triglycerides supporting the value of sensitive in vivo assays to define the functional nature of human haplotypes.

  1. HLA Haplotypes and Genotypes Frequencies in Brazilian Chronic Periodontitis Patients

    PubMed Central

    Sippert, Emília Ângela; Silva, Cléverson de Oliveira e; Ayo, Christiane Maria; Marques, Silvia Barbosa Dutra; Visentainer, Jeane Eliete Laguila; Sell, Ana Maria

    2015-01-01

    Human leukocyte antigens (HLA) have a pivotal role in immune response and may be involved in antigen recognition of periodontal pathogens. However, the associations of HLA with chronic periodontitis (CP) have not been previously studied in the Brazilian population. In an attempt to clarify the issue of genetic predisposition to CP, we examined the distribution of HLA alleles, genotypes, and haplotypes in patients from Southern Brazil. One hundred and eight CP patients and 151 healthy and unrelated controls with age-, gender-, and ethnicity-matched were HLA investigated by polymerase chain reaction with sequence specific oligonucleotides. To exclude smoking as a predisposing factor, statistical analyses were performed in the total sample and in nonsmoking individuals. The significant results showed a positive association of the A∗02/HLA-B∗40 haplotype with CP (total samples: 4.2% versus 0%, Pc = 0.03; nonsmokers: 4.3% versus 0%, Pc = 0.23) and a lower frequency of HLA-B∗15/HLA-DRB1∗11 haplotype in CP compared to controls (total samples: 0.0% versus 4.3%, Pc = 0.04; nonsmokers: 0 versus 5.1%, Pc = 1.0). In conclusion, the HLA-A∗02/B∗40 haplotype may contribute to the development of CP, while HLA-B∗15/DRB1∗11 haplotype might indicate resistance to disease among Brazilians. PMID:26339134

  2. Maximum parsimony xor haplotyping by sparse dictionary selection

    PubMed Central

    2013-01-01

    Background Xor-genotype is a cost-effective alternative to the genotype sequence of an individual. Recent methods developed for haplotype inference have aimed at finding the solution based on xor-genotype data. Given the xor-genotypes of a group of unrelated individuals, it is possible to infer the haplotype pairs for each individual with the aid of a small number of regular genotypes. Results We propose a framework of maximum parsimony inference of haplotypes based on the search of a sparse dictionary, and we present a greedy method that can effectively infer the haplotype pairs given a set of xor-genotypes augmented by a small number of regular genotypes. We test the performance of the proposed approach on synthetic data sets with different number of individuals and SNPs, and compare the performances with the state-of-the-art xor-haplotyping methods PPXH and XOR-HAPLOGEN. Conclusions Experimental results show good inference qualities for the proposed method under all circumstances, especially on large data sets. Results on a real database, CFTR, also demonstrate significantly better performance. The proposed algorithm is also capable of finding accurate solutions with missing data and/or typing errors. PMID:24059285

  3. High diversity of alpha-globin haplotypes in a Senegalese population, including many previously unreported variants.

    PubMed Central

    Martinson, J J; Excoffier, L; Swinburn, C; Boyce, A J; Harding, R M; Langaney, A; Clegg, J B

    1995-01-01

    RFLP haplotypes at the alpha-globin gene complex have been examined in 190 individuals from the Niokolo Mandenka population of Senegal: haplotypes were assigned unambiguously for 210 chromosomes. The Mandenka share with other African populations a sample size-independent haplotype diversity that is much greater than that in any non-African population: the number of haplotypes observed in the Mandenka is typically twice that seen in the non-African populations sampled to date. Of these haplotypes, 17.3% had not been observed in any previous surveys, and a further 19.1% have previously been reported only in African populations. The haplotype distribution shows clear differences between African and non-African peoples, but this is on the basis of population-specific haplotypes combined with haplotypes common to all. The relationship of the newly reported haplotypes to those previously recorded suggests that several mutation processes, particularly recombination as homologous exchange or gene conversion, have been involved in their production. A computer program based on the expectation-maximization (EM) algorithm was used to obtain maximum-likelihood estimates of haplotype frequencies for the entire data set: good concordance between the unambiguous and EM-derived sets was seen for the overall haplotype frequencies. Some of the low-frequency haplotypes reported by the estimation algorithm differ greatly, in structure, from those haplotypes known to be present in human populations, and they may not represent haplotypes actually present in the sample. PMID:7485171

  4. Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats.

    PubMed

    Babenko, Nataliya A; Garkavenko, Vladimir V; Storozhenko, Galina V; Timofiychuk, Olga A

    2016-04-01

    Old age-associated pathologies usually coincide with altered sphingolipid metabolism. In the present article, the role of acid sphingomyelinase (ASMase) in the age-dependent changes of sphingomyelin (SM) and ceramide contents in the tissues has been investigated by means of ASMase inhibitors, imipramine and zoledronic acid. It has been determined that ceramide content and ceramide/SM ratio increased, while SM level decreased in the heart, liver, blood serum and skeletal muscles of 24-month old rats in contrast to 3-month old animals. Injections of imipramine or zoledronic acid to 24-month old rats resulted in significant downregulation of ASMase in the liver and skeletal and heart muscles. The both inhibitors decreased the ceramide content and ceramide/SM ratio and increased the SM content in all tissues studied, except the heart, of old rats to the levels close to those observed in the young animals. Long-term treatment of rats by inhibitors, which have different mechanisms of action on ASMase, exerts the similar, but not equal effects on enzyme activity and SM turnover. In summary, the data above strongly suggest that the age-dependent up-regulation of ASMase plays an important role in the modulation of ceramide and SM contents in rat tissues and that imipramine and zoledronic acid are useful tools for SM turnover manipulation at old age. PMID:26830134

  5. A higher oxidative status accelerates senescence and aggravates age-dependent disorders in SAMP strains of mice.

    PubMed

    Hosokawa, Masanori

    2002-11-01

    The SAM strain of mice is actually a group of related inbred strains consisting of series of SAMP (accelerated senescence-prone, short-lived) and SAMR (accelerated senescence-resistant, longer-lived) strains. Comparing with the SAMR strains, the SAMP strains of mice show a more accelerated senescence process, shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to several geriatric disorders observed in humans, including senile osteoporosis, degenerative joint disease, age-related deficits in learning and memory, olfactory bulb and forebrain atrophy, presbycusis and retinal atrophy, senile amyloidosis, immunosenescence, senile lungs, and diffuse medial thickening of the aorta. The higher oxidative stress observed in the SAMP strains of mice are partly caused by mitochondrial dysfunction, and may be one cause of the senescence acceleration and age-dependent alterations in cell structure and function, including neuronal cell degeneration. This senescence acceleration is also observed during senescence/crisis in cultures of isolated fibroblast-like cells from SAMP strains of mice, and was associated with a hyperoxidative status. These observations suggest that the SAM strains are useful tools in the attempt to understand the mechanisms of age-dependent degeneration of cells and tissues, and their aggravation, and to develop clinical interventions. PMID:12470893

  6. Altered connexin 43 expression underlies age-dependent decrease of regulatory T cell suppressor function in nonobese diabetic mice.

    PubMed

    Kuczma, Michal; Wang, Cong-Yi; Ignatowicz, Leszek; Gourdie, Robert; Kraj, Piotr

    2015-06-01

    Type 1 diabetes is one of the most extensively studied autoimmune diseases, but the cellular and molecular mechanisms leading to T cell-mediated destruction of insulin-producing β cells are still not well understood. In this study, we show that regulatory T cells (T(regs)) in NOD mice undergo age-dependent loss of suppressor functions exacerbated by the decreased ability of activated effector T cells to upregulate Foxp3 and generate T(regs) in the peripheral organs. This age-dependent loss is associated with reduced intercellular communication mediated by gap junctions, which is caused by impaired upregulation and decreased expression of connexin 43. Regulatory functions can be corrected, even in T cells isolated from aged, diabetic mice, by a synergistic activity of retinoic acid, TGF-β, and IL-2, which enhance connexin 43 and Foxp3 expression in T(regs) and restore the ability of conventional CD4(+) T cells to upregulate Foxp3 and generate peripherally derived T(regs). Moreover, we demonstrate that suppression mediated by T(regs) from diabetic mice is enhanced by a novel reagent, which facilitates gap junction aggregation. In summary, our report identifies gap junction-mediated intercellular communication as an important component of the T(reg) suppression mechanism compromised in NOD mice and suggests how T(reg) mediated immune regulation can be improved. PMID:25911751

  7. Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons

    PubMed Central

    Cho, Kyoung-in; Yi, Haiqing; Yeh, Andrew; Tserentsoodol, Nomingerel; Cuadrado, Lori; Searle, Kelly; Hao, Ying; Ferreira, Paulo A.

    2008-01-01

    Prolonged light exposure is a determinant factor in inducing neurodegeneration of photoreceptors by apoptosis. Yet, the molecular bases of the pathways and components triggering this cell death event are elusive. Here, we reveal a prominent age-dependent increase in the susceptibility of photoreceptor neurons to undergo apoptosis under light in a mouse model. This is accompanied by light-induced subcellular changes of photoreceptors, such as dilation of the disks at the tip of the outer segments, prominent vesiculation of nascent disks, and autophagy of mitochondria into large multilamellar bodies. Notably, haploinsufficiency of Ran-binding protein-2 (RanBP2) suppresses apoptosis and most facets of membrane dysgenesis observed with age upon light-elicited stress. RanBP2 haploinsufficiency promotes decreased levels of free fatty acids in the retina independent of light exposure and turns the mice refractory to weight gain on a high-fat diet, whereas light promotes an increase in hydrogen peroxide regardless of the genotype. These studies demonstrate the presence of age-dependent and RanBP2-mediated pathways modulating membrane biogenesis of the outer segments and light-elicited neurodegeneration of photoreceptors. Furthermore, the findings support a mechanism whereby the RanBP2-dependent production of free fatty acids, metabolites thereof or the modulation of a cofactor dependent on any of these, promote apoptosis of photoreceptors in concert with the light-stimulated production of reactive oxygen species. PMID:18949001

  8. Age-dependent impairment of cognitive and synaptic function in the htau mouse model of tau pathology

    PubMed Central

    Polydoro, Manuela; Acker, Christopher M.; Duff, Karen; Castillo, Pablo E.; Davies, Peter

    2009-01-01

    A hallmark feature of Alzheimer’s disease pathology is the presence of neurofibrillary tangles (NFTs), which are intracellular aggregates of conformationally abnormal and hyperphosphorylated tau. The presence of NFTs in the forebrain is associated with impairments of cognitive function, supporting a central role for tau in dementia. The significance of the accumulation of NFTs for neuronal and cognitive function is still obscure. It is possible that NFTs disrupt synaptic transmission and plasticity, leading to memory deficits and cognitive malfunction. To elucidate the relationship between the development of tau pathology and synaptic and cognitive functions, we performed behavioral tests and electrophysiological experiments in the htau mouse. Here we report age-dependent cognitive and physiological impairments in htau mice which preceded neurodegeneration. 12-month-old htau mice with moderate tau pathology, but not 4-month-old mice with early stage tau pathology, presented cognitive deficits in an object recognition memory task in which the visual recognition memory of a novel object was disrupted. Moreover, only 12-month-old htau mice exhibit spatial memory deficits, as indicated by the impaired performance in the Morris water maze. In addition, we report that basal synaptic transmission and induction of long-term potentiation with high frequency stimulation, but not theta burst stimulation, is perturbed in hippocampal CA1 region of old but not young htau mice. Our results suggest that tau pathology may underlie an age-dependent learning impairment through disruption of synaptic function. PMID:19710325

  9. Age-dependent impairment of cognitive and synaptic function in the htau mouse model of tau pathology.

    PubMed

    Polydoro, Manuela; Acker, Christopher M; Duff, Karen; Castillo, Pablo E; Davies, Peter

    2009-08-26

    A hallmark feature of Alzheimer's disease pathology is the presence of neurofibrillary tangles (NFTs), which are intracellular aggregates of conformationally abnormal and hyperphosphorylated tau. The presence of NFTs in the forebrain is associated with impairments of cognitive function, supporting a central role for tau in dementia. The significance of the accumulation of NFTs for neuronal and cognitive function is still obscure. It is possible that NFTs disrupt synaptic transmission and plasticity, leading to memory deficits and cognitive malfunction. To elucidate the relationship between the development of tau pathology and synaptic and cognitive functions, we performed behavioral tests and electrophysiological experiments in the htau mouse. Here we report age-dependent cognitive and physiological impairments in htau mice that preceded neurodegeneration. Twelve-month-old htau mice with moderate tau pathology, but not 4-month-old mice with early-stage tau pathology, presented cognitive deficits in an object recognition memory task in which the visual recognition memory of a novel object was disrupted. Moreover, only 12-month-old htau mice exhibit spatial memory deficits, as indicated by the impaired performance in the Morris water maze. In addition, we report that basal synaptic transmission and induction of long-term potentiation with high-frequency stimulation, but not theta burst stimulation, is perturbed in hippocampal CA1 region of old but not young htau mice. Our results suggest that tau pathology may underlie an age-dependent learning impairment through disruption of synaptic function. PMID:19710325

  10. Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection

    PubMed Central

    Richner, Justin M.; Gmyrek, Grzegorz B.; Govero, Jennifer; Tu, Yizheng; van der Windt, Gerritje J. W.; Metcalf, Talibah U.; Haddad, Elias K.; Textor, Johannes; Miller, Mark J.; Diamond, Michael S.

    2015-01-01

    Impaired immune responses in the elderly lead to reduced vaccine efficacy and increased susceptibility to viral infections. Although several groups have documented age-dependent defects in adaptive immune priming, the deficits that occur prior to antigen encounter remain largely unexplored. Herein, we identify novel mechanisms for compromised adaptive immunity that occurs with aging in the context of infection with West Nile virus (WNV), an encephalitic flavivirus that preferentially causes disease in the elderly. An impaired IgM and IgG response and enhanced vulnerability to WNV infection during aging was linked to delayed germinal center formation in the draining lymph node (DLN). Adoptive transfer studies and two-photon intravital microscopy revealed a decreased trafficking capacity of donor naïve CD4+ T cells from old mice, which manifested as impaired T cell diapedesis at high endothelial venules and reduced cell motility within DLN prior to antigen encounter. Furthermore, leukocyte accumulation in the DLN within the first few days of WNV infection or antigen-adjuvant administration was diminished more generally in old mice and associated with a second aging-related defect in local cytokine and chemokine production. Thus, age-dependent cell-intrinsic and environmental defects in the DLN result in delayed immune cell recruitment and antigen recognition. These deficits compromise priming of early adaptive immune responses and likely contribute to the susceptibility of old animals to acute WNV infection. PMID:26204259

  11. Caspase-6 activity in the CA1 region of the hippocampus induces age-dependent memory impairment

    PubMed Central

    LeBlanc, A C; Ramcharitar, J; Afonso, V; Hamel, E; Bennett, D A; Pakavathkumar, P; Albrecht, S

    2014-01-01

    Active Caspase-6 is abundant in the neuropil threads, neuritic plaques and neurofibrillary tangles of Alzheimer disease brains. However, its contribution to the pathophysiology of Alzheimer disease is unclear. Here, we show that higher levels of Caspase-6 activity in the CA1 region of aged human hippocampi correlate with lower cognitive performance. To determine whether Caspase-6 activity, in the absence of plaques and tangles, is sufficient to cause memory deficits, we generated a transgenic knock-in mouse that expresses a self-activated form of human Caspase-6 in the CA1. This Caspase-6 mouse develops age-dependent spatial and episodic memory impairment. Caspase-6 induces neuronal degeneration and inflammation. We conclude that Caspase-6 activation in mouse CA1 neurons is sufficient to induce neuronal degeneration and age-dependent memory impairment. These results indicate that Caspase-6 activity in CA1 could be responsible for the lower cognitive performance of aged humans. Consequently, preventing or inhibiting Caspase-6 activity in the aged may provide an efficient novel therapeutic approach against Alzheimer disease. PMID:24413155

  12. Loss of FHL1 induces an age-dependent skeletal muscle myopathy associated with myofibrillar and intermyofibrillar disorganization in mice

    PubMed Central

    Domenighetti, Andrea A.; Chu, Pao-Hsien; Wu, Tongbin; Sheikh, Farah; Gokhin, David S.; Guo, Ling T.; Cui, Ziyou; Peter, Angela K.; Christodoulou, Danos C.; Parfenov, Michael G.; Gorham, Joshua M.; Li, Daniel Y.; Banerjee, Indroneal; Lai, Xianyin; Witzmann, Frank A.; Seidman, Christine E.; Seidman, Jonathan G.; Gomes, Aldrin V.; Shelton, G. Diane; Lieber, Richard L.; Chen, Ju

    2014-01-01

    Recent human genetic studies have provided evidences that sporadic or inherited missense mutations in four-and-a-half LIM domain protein 1 (FHL1), resulting in alterations in FHL1 protein expression, are associated with rare congenital myopathies, including reducing body myopathy and Emery–Dreifuss muscular dystrophy. However, it remains to be clarified whether mutations in FHL1 cause skeletal muscle remodeling owing to gain- or loss of FHL1 function. In this study, we used FHL1-null mice lacking global FHL1 expression to evaluate loss-of-function effects on skeletal muscle homeostasis. Histological and functional analyses of soleus, tibialis anterior and sternohyoideus muscles demonstrated that FHL1-null mice develop an age-dependent myopathy associated with myofibrillar and intermyofibrillar (mitochondrial and sarcoplasmic reticulum) disorganization, impaired muscle oxidative capacity and increased autophagic activity. A longitudinal study established decreased survival rates in FHL1-null mice, associated with age-dependent impairment of muscle contractile function and a significantly lower exercise capacity. Analysis of primary myoblasts isolated from FHL1-null muscles demonstrated early muscle fiber differentiation and maturation defects, which could be rescued by re-expression of the FHL1A isoform, highlighting that FHL1A is necessary for proper muscle fiber differentiation and maturation in vitro. Overall, our data show that loss of FHL1 function leads to myopathy in vivo and suggest that loss of function of FHL1 may be one of the mechanisms underlying muscle dystrophy in patients with FHL1 mutations. PMID:23975679

  13. Age-dependent gait abnormalities in mice lacking the Rnf170 gene linked to human autosomal-dominant sensory ataxia.

    PubMed

    Kim, Youngsoo; Kim, Seong Hun; Kim, Kook Hwan; Chae, Sujin; Kim, Chanki; Kim, Jeongjin; Shin, Hee-Sup; Lee, Myung-Shik; Kim, Daesoo

    2015-12-20

    Really interesting new gene (RING) finger protein 170 (RNF170) is an E3 ubiquitin ligase known to mediate ubiquitination-dependent degradation of type-I inositol 1,4,5-trisphosphate receptors (ITPR1). It has recently been demonstrated that a point mutation of RNF170 gene is linked with autosomal-dominant sensory ataxia (ADSA), which is characterized by an age-dependent increase of walking abnormalities, a rare genetic disorder reported in only two families. Although this mutant allele is known to be dominant, the functional identity thereof has not been clearly established. Here, we generated mice lacking Rnf170 (Rnf170(-/-)) to evaluate the effect of its loss of function in vivo. Remarkably, Rnf170(-/-) mice began to develop gait abnormalities in old age (12 months) in the form of asynchronous stepping between diagonal limb pairs with a fixed step sequence during locomotion, while age-matched wild-type mice showed stable gait patterns using several step sequence repertoires. As reported in ADSA patients, they also showed a reduced sensitivity for proprioception and thermal nociception. Protein blot analysis revealed that the amount of Itpr1 protein was significantly elevated in the cerebellum and spinal cord but intact in the cerebral cortex in Rnf170(-/-) mice. These results suggest that the loss of Rnf170 gene function mediates ADSA-associated phenotypes and this gives insights on the cure of patients with ADSA and other age-dependent walking abnormalities. PMID:26433933

  14. Haplotyping the human leukocyte antigen system from single chromosomes

    PubMed Central

    Murphy, Nicholas M.; Burton, Matthew; Powell, David R.; Rossello, Fernando J.; Cooper, Don; Chopra, Abha; Hsieh, Ming Je; Sayer, David C.; Gordon, Lavinia; Pertile, Mark D; Tait, Brian D.; Irving, Helen R.; Pouton, Colin W.

    2016-01-01

    We describe a method for determining the parental HLA haplotypes of a single individual without recourse to conventional segregation genetics. Blood samples were cultured to identify and sort chromosome 6 by bivariate flow cytometry. Single chromosome 6 amplification products were confirmed with a single nucleotide polymorphism (SNP) array and verified by deep sequencing to enable assignment of both alleles at the HLA loci, defining the two haplotypes. This study exemplifies a rapid and efficient method of haplotyping that can be applied to any chromosome pair, or indeed all chromosome pairs, using a single sorting operation. The method represents a cost-effective approach to complete phasing of SNPs, which will facilitate a deeper understanding of the links between SNPs, gene regulation and protein function. PMID:27461731

  15. Chloroquine-Resistant Haplotype Plasmodium falciparum Parasites, Haiti

    PubMed Central

    Londono, Berlin L.; Eisele, Thomas P.; Keating, Joseph; Bennett, Adam; Chattopadhyay, Chandon; Heyliger, Gaetan; Mack, Brian; Rawson, Ian; Vely, Jean-Francois; Désinor, Olbeg

    2009-01-01

    Plasmodium falciparum parasites have been endemic to Haiti for >40 years without evidence of chloroquine (CQ) resistance. In 2006 and 2007, we obtained blood smears for rapid diagnostic tests (RDTs) and filter paper blots of blood from 821 persons by passive and active case detection. P. falciparum infections diagnosed for 79 persons by blood smear or RDT were confirmed by PCR for the small subunit rRNA gene of P. falciparum. Amplification of the P. falciparum CQ resistance transporter (pfcrt) gene yielded 10 samples with amplicons resistant to cleavage by ApoI. A total of 5 of 9 samples had threonine at position 76 of pfcrt, which is consistent with CQ resistance (haplotypes at positions 72–76 were CVIET [n = 4] and CVMNT [n = 1]); 4 had only the wild-type haplotype associated with CQ susceptibility (CVMNK). These results indicate that CQ-resistant haplotype P. falciparum malaria parasites are present in Haiti. PMID:19402959

  16. Haplotyping the human leukocyte antigen system from single chromosomes.

    PubMed

    Murphy, Nicholas M; Burton, Matthew; Powell, David R; Rossello, Fernando J; Cooper, Don; Chopra, Abha; Hsieh, Ming Je; Sayer, David C; Gordon, Lavinia; Pertile, Mark D; Tait, Brian D; Irving, Helen R; Pouton, Colin W

    2016-01-01

    We describe a method for determining the parental HLA haplotypes of a single individual without recourse to conventional segregation genetics. Blood samples were cultured to identify and sort chromosome 6 by bivariate flow cytometry. Single chromosome 6 amplification products were confirmed with a single nucleotide polymorphism (SNP) array and verified by deep sequencing to enable assignment of both alleles at the HLA loci, defining the two haplotypes. This study exemplifies a rapid and efficient method of haplotyping that can be applied to any chromosome pair, or indeed all chromosome pairs, using a single sorting operation. The method represents a cost-effective approach to complete phasing of SNPs, which will facilitate a deeper understanding of the links between SNPs, gene regulation and protein function. PMID:27461731

  17. Rule-based induction method for haplotype comparison and identification of candidate disease loci

    PubMed Central

    2012-01-01

    There is a need for methods that are able to identify rare variants that cause low or moderate penetrance disease susceptibility. To answer this need, we introduce a rule-based haplotype comparison method, Haplous, which identifies haplotypes within multiple samples from phased genotype data and compares them within and between sample groups. We demonstrate that Haplous is able to accurately identify haplotypes that are identical by descent, exclude common haplotypes in the studied population and select rare haplotypes from the data. Our analysis of three families with multiple individuals affected by lymphoma identified several interesting haplotypes shared by distantly related patients. PMID:22429919

  18. Age-dependent Characteristics in Women with Breast Cancer: Mastectomy and Reconstructive Trends at an Urban Academic Institution.

    PubMed

    Rodby, Katherine A; Robinson, Emilie; Danielson, Kirstie K; Quinn, Karina P; Antony, Anuja K

    2016-03-01

    Breast reconstruction is an important aspect of treatment after breast cancer. Postmastectomy reconstruction bears a significant impact on a woman's postsurgical confidence, sexuality, and overall well-being. Previous studies have inferred that women under age 40 years have unique characteristics that distinguish them from an older cohort. Identifying age-dependent trends will assist with counseling women on mastectomy and reconstruction. To identify age-dependent trends, 100 consecutive women were sampled from a prospectively maintained breast reconstruction database at an urban academic institution from June 2010 through June 2013. Women were placed into two cohorts <40 and ≥40 as well cohorts by decade (20s, 30s, 40s, 50s, and 60s). Statistical trends were reported as odds of risk per year of increasing age using logistic regression; linear regression, χ(2), and Fischer's exact were used to compare <40 and ≥40 and split cohorts for comparison. Comorbidities, tumor staging, oncologic treatment including chemotherapy and radiation, disease characteristics and genetics, and mastectomy, reconstructive and symmetry procedures were evaluated. Statistical analysis was performed using SAS software. In 100 patients of the sample study cohort, 151 reconstructions were performed. Increasing age was associated with one or more comorbidities [odds ratio (OR) = 1.07, P = 0.005], whereas younger age was associated with metastatic disease (OR = 0.88, P = 0.006), chemotherapy (OR = 0.94, P = 0.01), and radiation (OR = 0.94, P = 0.006); split cohorts demonstrated similar trends (P < 0.005). Mastectomy and reconstructive characteristics associated with younger age included bilateral mastectomy (OR = 0.94, P = 0.004), tissue expander (versus autologous flap) (OR = 0.94, P = 0.009), extra high implant type (OR = 0.94, P = 0.049), whereas increasing use of autologous flaps and contralateral mastopexy symmetry procedures (OR = 1.09, P = 0.02) were associated with an aging cohort

  19. Detecting disease-predisposing variants: The haplotype method

    SciTech Connect

    Valdes, A.M.; Thomson, G.

    1997-03-01

    For many HLA-associated diseases, multiple alleles - and, in some cases, multiple loci - have been suggested as the causative agents. The haplotype method for identifying disease-predisposing amino acids in a genetic region is a stratification analysis. We show that, for each haplotype combination containing all the amino acid sites involved in the disease process, the relative frequencies of amino acid variants at sites not involved in disease but in linkage disequilibrium with the disease-predisposing sites are expected to be the same in patients and controls. The haplotype method is robust to mode of inheritance and penetrance of the disease and can be used to determine unequivocally whether all amino acid sites involved in the disease have not been identified. Using a resampling technique, we developed a statistical test that takes account of the nonindependence of the sites sampled. Further, when multiple sites in the genetic region are involved in disease, the test statistic gives a closer fit to the null expectation when some - compared with none - of the true predisposing factors are included in the haplotype analysis. Although the haplotype method cannot distinguish between very highly correlated sites in one population, ethnic comparisons may help identify the true predisposing factors. The haplotype method was applied to insulin-dependent diabetes mellitus (IDDM) HLA class II DQA1-DQB1 data from Caucasian, African, and Japanese populations. Our results indicate that the combination DQA1 No. 52 (Arg predisposing) DQB1 No. 57 (Asp protective), which has been proposed as an important IDDM agent, does not include all the predisposing elements. With rheumatoid arthritis HLA class H DRB1 data, the results were consistent with the shared-epitope hypothesis. 35 refs., 2 figs., 6 tabs.

  20. Prion gene haplotypes of U.S. cattle

    PubMed Central

    Clawson, Michael L; Heaton, Michael P; Keele, John W; Smith, Timothy PL; Harhay, Gregory P; Laegreid, William W

    2006-01-01

    Background Bovine spongiform encephalopathy (BSE) is a fatal neurological disorder characterized by abnormal deposits of a protease-resistant isoform of the prion protein. Characterizing linkage disequilibrium (LD) and haplotype networks within the bovine prion gene (PRNP) is important for 1) testing rare or common PRNP variation for an association with BSE and 2) interpreting any association of PRNP alleles with BSE susceptibility. The objective of this study was to identify polymorphisms and haplotypes within PRNP from the promoter region through the 3'UTR in a diverse sample of U.S. cattle genomes. Results A 25.2-kb genomic region containing PRNP was sequenced from 192 diverse U.S. beef and dairy cattle. Sequence analyses identified 388 total polymorphisms, of which 287 have not previously been reported. The polymorphism alleles define PRNP by regions of high and low LD. High LD is present between alleles in the promoter region through exon 2 (6.7 kb). PRNP alleles within the majority of intron 2, the entire coding sequence and the untranslated region of exon 3 are in low LD (18.0 kb). Two haplotype networks, one representing the region of high LD and the other the region of low LD yielded nineteen different combinations that represent haplotypes spanning PRNP. The haplotype combinations are tagged by 19 polymorphisms (htSNPS) which characterize variation within and across PRNP. Conclusion The number of polymorphisms in the prion gene region of U.S. cattle is nearly four times greater than previously described. These polymorphisms define PRNP haplotypes that may influence BSE susceptibility in cattle. PMID:17092337

  1. On the Estimation of Parameters and the Evaluation of a Mathematical Model: A Reply to Pascual-Leone

    ERIC Educational Resources Information Center

    Trabasso, Tom

    1978-01-01

    A reply to a rejoinder in which Pascual-Leone defended his quantitative model of children's information processing capacity. Trabasso focuses on empirical evidence in presenting his reply to this rejoinder. (BD)

  2. Defects of Lipid Synthesis Are Linked to the Age-Dependent Demyelination Caused by Lamin B1 Overexpression

    PubMed Central

    Rolyan, Harshvardhan; Tyurina, Yulia Y.; Hernandez, Marylens; Amoscato, Andrew A.; Sparvero, Louis J.; Nmezi, Bruce C.; Lu, Yue; Estécio, Marcos R. H.; Lin, Kevin; Chen, Junda; He, Rong-Rong; Gong, Pin; Rigatti, Lora H.; Dupree, Jeffrey; Bayır, Hülya; Kagan, Valerian E.; Casaccia, Patrizia

    2015-01-01

    Lamin B1 is a component of the nuclear lamina and plays a critical role in maintaining nuclear architecture, regulating gene expression and modulating chromatin positioning. We have previously shown that LMNB1 gene duplications cause autosomal dominant leukodystrophy (ADLD), a fatal adult onset demyelinating disease. The mechanisms by which increased LMNB1 levels cause ADLD are unclear. To address this, we used a transgenic mouse model where Lamin B1 overexpression is targeted to oligodendrocytes. These mice showed severe vacuolar degeneration of the spinal cord white matter together with marked astrogliosis, microglial infiltration, and secondary axonal damage. Oligodendrocytes in the transgenic mice revealed alterations in histone modifications favoring a transcriptionally repressed state. Chromatin changes were accompanied by reduced expression of genes involved in lipid synthesis pathways, many of which are known to play important roles in myelin regulation and are preferentially expressed in oligodendrocytes. Decreased lipogenic gene expression resulted in a significant reduction in multiple classes of lipids involved in myelin formation. Many of these gene expression changes and lipid alterations were observed even before the onset of the phenotype, suggesting a causal role. Our findings establish, for the first time, a link between LMNB1 and lipid synthesis in oligodendrocytes, and provide a mechanistic framework to explain the age dependence and white matter involvement of the disease phenotype. These results have implications for disease pathogenesis and may also shed light on the regulation of lipid synthesis pathways in myelin maintenance and turnover. SIGNIFICANCE STATEMENT Autosomal dominant leukodystrophy (ADLD) is fatal neurological disorder caused by increased levels of the nuclear protein, Lamin B1. The disease is characterized by an age-dependent loss of myelin, the fatty sheath that covers nerve fibers. We have studied a mouse model where Lamin B

  3. Strain- and Age-dependent Hippocampal Neuron Sodium Currents Correlate with Epilepsy Severity in Dravet Syndrome Mice

    PubMed Central

    Mistry, Akshitkumar M.; Thompson, Christopher H.; Miller, Alison R.; Vanoye, Carlos G.; George, Alfred L.; Kearney, Jennifer A.

    2014-01-01

    Heterozygous loss-of-function SCN1A mutations cause Dravet syndrome, an epileptic encephalopathy of infancy that exhibits variable clinical severity. We utilized a heterozygous Scn1a knockout (Scn1a+/−) mouse model of Dravet syndrome to investigate the basis for phenotype variability. These animals exhibit strain-dependent seizure severity and survival. Scn1a+/− mice on strain 129S6/SvEvTac (129.Scn1a+/−) have no overt phenotype and normal survival compared with Scn1a+/− mice bred to C57BL/6J (F1.Scn1a+/−) that have severe epilepsy and premature lethality. We tested the hypothesis that strain differences in sodium current (INa) density in hippocampal neurons contribute to these divergent phenotypes. Whole-cell voltage-clamp recording was performed on acutely-dissociated hippocampal neurons from postnatal day 21–24 (P21–24) 129.Scn1a+/− or F1.Scn1a+/− mice and wild-type littermates. INa density was lower in GABAergic interneurons from F1.Scn1a+/− mice compared to wild-type littermates, while on the 129 strain there was no difference in GABAergic interneuron INa between 129.Scn1a+/− mice and wild-type littermate controls. By contrast, INa density was elevated in pyramidal neurons from both 129.Scn1a+/− and F1.Scn1a+/− mice, and was correlated with more frequent spontaneous action potential firing in these neurons, as well as more sustained firing in F1.Scn1a+/− neurons. We also observed age-dependent differences in pyramidal neuron INa density between wild-type and Scn1a+/− animals. We conclude that preserved INa density in GABAergic interneurons contributes to the milder phenotype of 129.Scn1a+/− mice. Furthermore, elevated INa density in excitatory pyramidal neurons at P21–24 correlates with age-dependent onset of lethality in F1.Scn1a+/− mice. Our findings illustrate differences in hippocampal neurons that may underlie strain- and age-dependent phenotype severity in a Dravet syndrome mouse model, and emphasize a contribution of

  4. Glucocorticoid receptor gene haplotype structure and steroid therapy outcome in IBD patients

    PubMed Central

    Mwinyi, Jessica; Wenger, Christa; Eloranta, Jyrki J; Kullak-Ublick, Gerd A

    2010-01-01

    AIM: To study whether the glucocorticoid receptor (GR/NR3C1) gene haplotypes influence the steroid therapy outcome in inflammatory bowel disease (IBD). METHODS: We sequenced all coding exons and flanking intronic sequences of the NR3C1 gene in 181 IBD patients, determined the single nucleotide polymorphisms, and predicted the NR3C1 haplotypes. Furthermore, we investigated whether certain NR3C1 haplotypes are significantly associated with steroid therapy outcomes. RESULTS: We detected 13 NR3C1 variants, which led to the formation of 17 different haplotypes with a certainty of > 95% in 173 individuals. The three most commonly occurring haplotypes were included in the association analysis of the influence of haplotype on steroid therapy outcome or IBD activity. None of the NR3C1 haplotypes showed statistically significant association with glucocorticoid therapy success. CONCLUSION: NR3C1 haplotypes are not related to steroid therapy outcome. PMID:20712049

  5. Age-dependent changes in lipid peroxide levels in peripheral organs, but not in brain, in senescence-accelerated mice.

    PubMed

    Matsugo, S; Kitagawa, T; Minami, S; Esashi, Y; Oomura, Y; Tokumaru, S; Kojo, S; Matsushima, K; Sasaki, K

    2000-01-01

    The tissue concentration of lipid peroxides was determined in the brain, heart, liver, lung and kidney of accelerated senescence-prone (SAMP-8) and -resistant (SAMR-1) mice at 3, 6 and 9 months of age by a method involving chemical derivatization and high performance liquid chromatography. The level of lipid peroxides in the brain did not show an age-dependent change, but at each age the brain level of lipid peroxides was significantly higher in SAMP-8 than in SAMR-1. In contrast, the lipid peroxide levels in the peripheral organs showed increases with aging in both strains, and they were significantly higher in SAMP-8 than in SAMR-1 at both 3 and 6 months of age (except at 3 months of age in the kidney). These results suggest that increased oxidative stress in the brain and peripheral organs is a cause of the senescence-related degeneration and impairments seen in SAMP-8. PMID:10643812

  6. TIEG1-null tenocytes display age-dependent differences in their gene expression, adhesion, spreading and proliferation properties

    SciTech Connect

    Haddad, Oualid; Gumez, Laurie; Hawse, John R.; Subramaniam, Malayannan; Spelsberg, Thomas C.; Bensamoun, Sabine F.

    2011-07-15

    The remodeling of extracellular matrix is a crucial mechanism in tendon development and the proliferation of fibroblasts is a key factor in this process. The purpose of this study was to further elucidate the role of TIEG1 in mediating important tenocyte properties throughout the aging process. Wildtype and TIEG1 knockout tenocytes adhesion, spreading and proliferation were characterized on different substrates (fibronectin, collagen type I, gelatin and laminin) and the expression levels of various genes known to be involved with tendon development were analyzed by RT-PCR. The experiments revealed age-dependent and substrate-dependent properties for both wildtype and TIEG1 knockout tenocytes. Taken together, our results indicate an important role for TIEG1 in regulating tenocytes adhesion, spreading, and proliferation throughout the aging process. Understanding the basic mechanisms of TIEG1 in tenocytes may provide valuable information for treating multiple tendon disorders.

  7. Evidence for an Age-Dependent Decline in Axon Regeneration in the Adult Mammalian Central Nervous System.

    PubMed

    Geoffroy, Cédric G; Hilton, Brett J; Tetzlaff, Wolfram; Zheng, Binhai

    2016-04-12

    How aging impacts axon regeneration after CNS injury is not known. We assessed the impact of age on axon regeneration induced by Pten deletion in corticospinal and rubrospinal neurons, two neuronal populations with distinct innate regenerative abilities. As in young mice, Pten deletion in older mice remains effective in preventing axotomy-induced decline in neuron-intrinsic growth state, as assessed by mTOR activity, neuronal soma size, and axonal growth proximal to a spinal cord injury. However, axonal regeneration distal to injury is greatly diminished, accompanied by increased expression of astroglial and inflammatory markers at the injury site. Thus, the mammalian CNS undergoes an age-dependent decline in axon regeneration, as revealed when neuron-intrinsic growth state is elevated. These results have important implications for developing strategies to promote axonal repair after CNS injuries or diseases, which increasingly affect middle-aged to aging populations. PMID:27050519

  8. Age-dependent susceptibilities of Bulinus truncatus snails to an aqueous extract of Pulicaria crispa (Forssk.) Oliv. (Asteraceae) leaves.

    PubMed

    Ali, Elnour A; Bushara, Hamid O; Ali, Faisal S; Hussein, Mansour F

    2009-05-01

    This study was carried out to investigate the potential use of the herb Pulicaria crispa in the biological control of different developmental stages of Bulinus truncatus, a major snail intermediate host of urinary schistosomiasis. Age-dependent susceptibilities of mature adult snails, immature snails, juveniles, and one-day old egg masses to aqueous extracts of Pulicaria crispa leaves collected from Khartoum (Sudan) and Riyadh (Saudi Arabia) was determined and compared. The results show the juvenile snails are the most susceptible, followed in descending order by one-day old egg masses, immature snails, and mature adult snails. The P. crispa sample collected from Riyadh was significantly more potent against B. truncatus than that collected from Khartoum, as indicated by the least (LC50) and (LC90) values for all B. truncatus ages. PMID:19842431

  9. Genetics of chloroquine-resistant malaria: a haplotypic view

    PubMed Central

    Awasthi, Gauri; Das, Aparup

    2013-01-01

    The development and rapid spread of chloroquine resistance (CQR) in Plasmodium falciparum have triggered the identification of several genetic target(s) in the P. falciparum genome. In particular, mutations in the Pfcrt gene, specifically, K76T and mutations in three other amino acids in the region adjoining K76 (residues 72, 74, 75 and 76), are considered to be highly related to CQR. These various mutations form several different haplotypes and Pfcrt gene polymorphisms and the global distribution of the different CQR- Pfcrt haplotypes in endemic and non-endemic regions of P. falciparum malaria have been the subject of extensive study. Despite the fact that the Pfcrt gene is considered to be the primary CQR gene in P. falciparum , several studies have suggested that this may not be the case. Furthermore, there is a poor correlation between the evolutionary implications of the Pfcrt haplotypes and the inferred migration of CQR P. falciparum based on CQR epidemiological surveillance data. The present paper aims to clarify the existing knowledge on the genetic basis of the different CQR- Pfcrt haplotypes that are prevalent in worldwide populations based on the published literature and to analyse the data to generate hypotheses on the genetics and evolution of CQR malaria. PMID:24402147

  10. Fast Sampling-Based Whole-Genome Haplotype Block Recognition.

    PubMed

    Taliun, Daniel; Gamper, Johann; Leser, Ulf; Pattaro, Cristian

    2016-01-01

    Scaling linkage disequilibrium (LD) based haplotype block recognition to the entire human genome has always been a challenge. The best-known algorithm has quadratic runtime complexity and, even when sophisticated search space pruning is applied, still requires several days of computations. Here, we propose a novel sampling-based algorithm, called S-MIG (++), where the main idea is to estimate the area that most likely contains all haplotype blocks by sampling a very small number of SNP pairs. A subsequent refinement step computes the exact blocks by considering only the SNP pairs within the estimated area. This approach significantly reduces the number of computed LD statistics, making the recognition of haplotype blocks very fast. We theoretically and empirically prove that the area containing all haplotype blocks can be estimated with a very high degree of certainty. Through experiments on the 243,080 SNPs on chromosome 20 from the 1,000 Genomes Project, we compared our previous algorithm MIG (++) with the new S-MIG (++) and observed a runtime reduction from 2.8 weeks to 34.8 hours. In a parallelized version of the S-MIG (++) algorithm using 32 parallel processes, the runtime was further reduced to 5.1 hours. PMID:27045830

  11. Better ILP-Based Approaches to Haplotype Assembly.

    PubMed

    Chen, Zhi-Zhong; Deng, Fei; Shen, Chao; Wang, Yiji; Wang, Lusheng

    2016-07-01

    Haplotype assembly is to directly construct the haplotypes of an individual from sequence fragments (reads) of the individual. Although a number of programs have been designed for computing optimal or heuristic solutions to the haplotype assembly problem, computing an optimal solution may take days or even months while computing a heuristic solution usually requires a trade-off between speed and accuracy. This article refines a previously known integer linear programming-based (ILP-based) approach to the haplotype assembly problem in twofolds. First, the read-matrices of some datasets (such as NA12878) come with a quality for each base in the reads. We here propose to utilize the qualities in the ILP-based approach. Secondly, we propose to use the ILP-based approach to improve the output of any heuristic program for the problem. Experiments with both real and simulated datasets show that the qualities of read-matrices help us find more accurate solutions without significant loss of speed. Moreover, our experimental results show that the proposed hybrid approach improves the output of ReFHap (the current leading heuristic) significantly (say, by almost 25% of the QAN50 score) without significant loss of speed, and can even find optimal solutions in much shorter time than the original ILP-based approach. Our program is available upon request to the authors. PMID:27347882

  12. Nomenclature of mitochondrial DNA haplotypes for Oncorhynchus mykiss

    USGS Publications Warehouse

    Graziano, Sara L.; Brown, K.H.; Nielsen, Jennifer L.

    2005-01-01

    Congruence of genetic data is critical for comparative and collaborative studies on natural fish populations. A comprehensive list of reported mitochrondrial DNA haplotypes for Oncorhynchus mykiss generated using the S-Phe/P2 primer set is presented as a resource for future investigations of this species.

  13. Ashkenazi levites' "Y modal haplotype" (LMH)-- an artificially created phenomenon?

    PubMed

    Zoossmann-Diskin, A

    2006-01-01

    The article on the Y chromosomes of Ashkenazi Levites (Behar et al., 2003. Am. J. Hum. Genet. 73, 768-779) is the fourth in a series on the Y chromosomes of the three Jewish male castes: Cohanim (priests), Levites (priests' helpers) and Israelites (lay people). It became apparent that there is a problem with omission of samples when the second article "Origins of Old Testament priests" (Thomas et al., 1998. Nature 394, 138-140) was published. In the fourth article a remarkable 55% of the Ashkenazi Levite samples from the earlier 1998 study are not included. This causes the "Levite modal haplotype" to double its frequency from 21% of the Ashkenazi Levite sample in 1998 to 42% of the Ashkenazi Levite sample in 2003. The authors offer three main explanations: (1) The studies are independent using different sample sets.(2) Typing errors and poor quality exclude samples from future studies.(3) Correction of typing errors means that some samples are classified under different haplotypes. The explanations offered to the problem of omitting samples from subsequent studies after their haplotypes or partial haplotypes are known, are not convincing. Consequently their sample sets cannot be considered random and non-biased. At the least, these laboratories have bad practices of sample handling and many typing errors, which are enough to invalidate their studies. PMID:16427053

  14. Reporting of haplotypes with recessive effects on fertility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic discovery of five haplotypes with recessive effects on fertility requires new automated tracking methods for QTL causing embryo loss in breeding programs. Most of the losses are early in gestation. Approximate locations of the five QTL were refined using crossovers detected within the pedigr...

  15. Nomenclature of mitochondrial DNA haplotypes for Oncorhynchus mykiss

    USGS Publications Warehouse

    Graziano, S.L.; Brown, K.H.; Nielsen, J.L.

    2005-01-01

    Congruence of genetic data is critical for comparative and collaborative studies on natural fish populations. A comprehensive list of reported mitochrondrial DNA haplotypes for Oncorhynchus mykiss generated using the S-Phe/P2 primer set is presented as a resource for future investigations of this species. ?? Copyright by the American Fisheries Society 2005.

  16. Polymorphisms and haplotype structure of bovine PRND (doppel) and PRNT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE) is a fatal neurological disorder characterized by abnormal deposits of a protease-resistant isoform of the prion protein. In previous studies, we have characterized linkage disequilibrium (LD) and haplotype networks within the bovine prion gene (PRNP). Other ...

  17. Haplotypes of 'Candidatus Liberibacter solanacearum' suggest long-standing separation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three haplotypes of the recently discovered bacterium species “Candidatus Liberibacter solanacearum” are described and related to geographic ranges. The first two are associated with Zebra Chip/Psyllid Yellows of potatoes and other solanaceous plants, vectored by the tomato/potato psyllid Bacterice...

  18. Age-dependent effects of severe traumatic brain injury on cerebral dopaminergic activity in newborn and juvenile pigs.

    PubMed

    Walter, Bernd; Brust, Peter; Füchtner, Frank; Müller, Marco; Hinz, Rainer; Kuwabara, Hiroto; Fritz, Harald; Zwiener, Ulrich; Bauer, Reinhard

    2004-08-01

    There is evidence that the dopaminergic system is sensitive to traumatic brain injury (TBI). However, the age-dependency of this sensitivity has not been studied together with brain oxidative metabolism. We postulate that the acute effects of severe TBI on brain dopamine turnover are age-dependent. Therefore 18F-labelled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with Positron-Emission-Tomography (PET) was used to estimate the activity of the aromatic amino acid decarboxylase (AADC) in the brain of 11 newborn piglets (7-10 days old) and nine juvenile pigs (6-7 weeks old). Six newborn and five juvenile animals were subjected to a severe fluid-percussion (FP) induced TBI. The remaining animals were used as sham operated untreated control groups. Simultaneously, the regional cerebral blood flow (CBF) was measured with colored microspheres and the cerebral metabolic rates of oxygen and glucose were determined. At 1 h after FP-TBI, [18F]FDOPA was infused and PET scanning was performed for 2 h. At 2 h after FP-TBI administration, a second series of measurements of physiological values including CBF and brain oxidative metabolism data had been obtained. Severe FP-TBI elicited a marked increase in the rate constant for fluorodopamine production (k3FDOPA) in all brain regions of newborn piglets studied by between 97% (mesencephalon) and 143% (frontal cortex) (p < 0.05). In contrast, brain hemodynamics and cerebral oxidative metabolism remained unaltered after TBI. Furthermore, the permeability-surface area product of FDOPA (PSFDOPA) was unchanged. In addition, regional blood flow differences between corresponding ipsi- and contralateral brain regions did not occur after TBI. Thus, it is suggested that severe FP-TBI induces an upregulation of AADC activity of newborn piglets that is not related to alterations in brain oxidative metabolism. PMID:15319007

  19. An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

    SciTech Connect

    Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

    2007-08-01

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometrically scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.

  20. Cell cycle age dependence for radiation-induced G/sub 2/ arrest: evidence for time-dependent repair

    SciTech Connect

    Rowley, R.

    1985-09-01

    Exponentially growing eucaryotic cells, irradiated in interphase, are delayed in progression to mitosis chiefly by arrest in G/sub 2/. The sensitivity of Chinese hamster ovary cells to G/sub 2/ arrest induction by X rays increases through the cell cycle, up to the X-ray transition point (TP) in G/sub 2/. This age response can be explained by cell cycle age-dependent changes in susceptibility of the target(s) for G/sub 2/ arrest and/or by changes in capability for postirradiation recovery from G/sub 2/ arrest damage. Discrimination between sensitivity changes and repair phenomena is possible only if the level of G/sub 2/ arrest-causing damage sustained by a cell at the time of irradiation and the level ultimately expressed as arrest can be determined. The ability of caffeine to ameliorate radiation-induced G/sub 2/ arrest, while inhibiting repair of G/sub 2/ arrest-causing damage makes such an analysis possible. In the presence of caffeine, progression of irradiated cells was relatively unperturbed, but on caffeine removal, G/sub 2/ arrest was expressed. The duration of G/sub 2/ arrest was independent of the length of the prior caffeine exposure. This finding indicates that the target for G/sub 2/ arrest induction is present throughout the cell cycle and that the level of G/sub 2/ arrest damage incurred is initially constant for all cell cycle phases. The data are consistent with the existence of a time-dependent recovery mechanism to explain the age dependence for radiation induction of G/sub 2/ arrest.

  1. Age-Dependent Decline in Mouse Lung Regeneration with Loss of Lung Fibroblast Clonogenicity and Increased Myofibroblastic Differentiation

    PubMed Central

    Paxson, Julia A.; Gruntman, Alisha; Parkin, Christopher D.; Mazan, Melissa R.; Davis, Airiel; Ingenito, Edward P.; Hoffman, Andrew M.

    2011-01-01

    While aging leads to a reduction in the capacity for regeneration after pneumonectomy (PNX) in most mammals, this biological phenomenon has not been characterized over the lifetime of mice. We measured the age-specific (3, 9, 24 month) effects of PNX on physiology, morphometry, cell proliferation and apoptosis, global gene expression, and lung fibroblast phenotype and clonogenicity in female C57BL6 mice. The data show that only 3 month old mice were fully capable of restoring lung volumes by day 7 and total alveolar surface area by 21 days. By 9 months, the rate of regeneration was slower (with incomplete regeneration by 21 days), and by 24 months there was no regrowth 21 days post-PNX. The early decline in regeneration rate was not associated with changes in alveolar epithelial cell type II (AECII) proliferation or apoptosis rate. However, significant apoptosis and lack of cell proliferation was evident after PNX in both total cells and AECII cells in 24 mo mice. Analysis of gene expression at several time points (1, 3 and 7 days) post-PNX in 9 versus 3 month mice was consistent with a myofibroblast signature (increased Tnc, Lox1, Col3A1, Eln and Tnfrsf12a) and more alpha smooth muscle actin (αSMA) positive myofibroblasts were present after PNX in 9 month than 3 month mice. Isolated lung fibroblasts showed a significant age-dependent loss of clonogenicity. Moreover, lung fibroblasts isolated from 9 and 17 month mice exhibited higher αSMA, Col3A1, Fn1 and S100A expression, and lower expression of the survival gene Mdk consistent with terminal differentiation. These data show that concomitant loss of clonogenicity and progressive myofibroblastic differentiation contributes to the age-dependent decline in the rate of lung regeneration. PMID:21912590

  2. Simulated Microgravity Exerts an Age-Dependent Effect on the Differentiation of Cardiovascular Progenitors Isolated from the Human Heart.

    PubMed

    Fuentes, Tania I; Appleby, Nancy; Raya, Michael; Bailey, Leonard; Hasaniya, Nahidh; Stodieck, Louis; Kearns-Jonker, Mary

    2015-01-01

    Microgravity has a profound effect on cardiovascular function, however, little is known about the impact of microgravity on progenitors that reside within the heart. We investigated the effect of simulated microgravity exposure on progenitors isolated from the neonatal and adult human heart by quantifying changes in functional parameters, gene expression and protein levels after 6-7 days of 2D clinorotation. Utilization of neonatal and adult cardiovascular progenitors in ground-based studies has provided novel insight into how microgravity may affect cells differently depending on age. Simulated microgravity exposure did not impact AKT or ERK phosphorylation levels and did not influence cell migration, but elevated transcripts for paracrine factors were identified in neonatal and adult cardiovascular progenitors. Age-dependent responses surfaced when comparing the impact of microgravity on differentiation. Endothelial cell tube formation was unchanged or increased in progenitors from adults whereas neonatal cardiovascular progenitors showed a decline in tube formation (p<0.05). Von Willebrand Factor, an endothelial differentiation marker, and MLC2v and Troponin T, markers for cardiomyogenic differentiation, were elevated in expression in adult progenitors after simulated microgravity. DNA repair genes and telomerase reverse transcriptase which are highly expressed in early stem cells were increased in expression in neonatal but not adult cardiac progenitors after growth under simulated microgravity conditions. Neonatal cardiac progenitors demonstrated higher levels of MESP1, OCT4, and brachyury, markers for early stem cells. MicroRNA profiling was used to further investigate the impact of simulated microgravity on cardiovascular progenitors. Fifteen microRNAs were significantly altered in expression, including microRNAs-99a and 100 (which play a critical role in cell dedifferentiation). These microRNAs were unchanged in adult cardiac progenitors. The effect of

  3. GABRB2 Haplotype Association with Heroin Dependence in Chinese Population

    PubMed Central

    Kim, Yung Su; Yang, Mei; Mat, Wai-Kin; Tsang, Shui-Ying; Su, Zhonghua; Jiang, Xianfei; Ng, Siu-Kin; Liu, Siyu; Hu, Taobo; Pun, Frank; Liao, Yanhui; Tang, Jinsong; Chen, Xiaogang; Hao, Wei; Xue, Hong

    2015-01-01

    Substance dependence is a frequently observed comorbid disorder in schizophrenia, but little is known about genetic factors possibly shared between the two psychotic disorders. GABRB2, a schizophrenia candidate gene coding for GABAA receptor β2 subunit, is examined for possible association with heroin dependence in Han Chinese population. Four single nucleotide polymorphisms (SNPs) in GABRB2, namely rs6556547 (S1), rs1816071 (S3), rs18016072 (S5), and rs187269 (S29), previously associated with schizophrenia, were examined for their association with heroin dependence. Two additional SNPs, rs10051667 (S31) and rs967771 (S32), previously associated with alcohol dependence and bipolar disorder respectively, were also analyzed. The six SNPs were genotyped by direct sequencing of PCR amplicons of target regions for 564 heroin dependent individuals and 498 controls of Han Chinese origin. Interestingly, it was found that recombination between the haplotypes of all-derived-allele (H1; OR = 1.00) and all-ancestral-allele (H2; OR = 0.74) at S5-S29 junction generated two recombinants H3 (OR = 8.51) and H4 (OR = 5.58), both conferring high susceptibility to heroin dependence. Additional recombination between H2 and H3 haplotypes at S1-S3 junction resulted in a risk-conferring haplotype H5 (OR = 1.94x109). In contrast, recombination between H1 and H2 haplotypes at S3-S5 junction rescued the risk-conferring effect of recombination at S5-S29 junction, giving rise to the protective haplotype H6 (OR = 0.68). Risk-conferring effects of S1-S3 and S5-S29 crossovers and protective effects of S3-S5 crossover were seen in both pure heroin dependent and multiple substance dependence subgroups. In conclusion, significant association was found with haplotypes of the S1-S29 segment in GABRB2 for heroin dependence in Han Chinese population. Local recombination was an important determining factor for switching haplotypes between risk-conferring and protective statuses. The present study

  4. Comprehensive Yet Scalable Health Information Systems for Low Resource Settings: A Collaborative Effort in Sierra Leone

    PubMed Central

    Braa, Jørn; Kanter, Andrew S.; Lesh, Neal; Crichton, Ryan; Jolliffe, Bob; Sæbø, Johan; Kossi, Edem; Seebregts, Christopher J.

    2010-01-01

    We address the problem of how to integrate health information systems in low-income African countries in which technical infrastructure and human resources vary wildly within countries. We describe a set of tools to meet the needs of different service areas including managing aggregate indicators, patient level record systems, and mobile tools for community outreach. We present the case of Sierra Leone and use this case to motivate and illustrate an architecture that allows us to provide services at each level of the health system (national, regional, facility and community) and provide different configurations of the tools as appropriate for the individual area. Finally, we present a, collaborative implementation of this approach in Sierra Leone. PMID:21347003

  5. Female genital mutilation in Sierra Leone: who are the decision makers?

    PubMed

    Bjälkander, Owolabi; Leigh, Bailah; Harman, Grace; Bergström, Staffan; Almroth, Lars

    2012-12-01

    The objectives of this study were to identify decision makers for FGM and determine whether medicalization takes place in Sierra Leone. Structured interviews were conducted with 310 randomly selected girls between 10 and 20 years in Bombali and Port Loko Districts in Northern Sierra Leone. The average age of the girls in this sample was 14 years, 61% had undergone FGM at an average age of 7.7 years (range 1-18). Generally, decisions to perform FGM were made by women, but father was mentioned as the one who decided by 28% of the respondents. The traditional excisors (Soweis) performed 80% of all operations, health professionals 13%, and traditional birth attendants 6%. Men may play a more important role in the decision making process in relation to FGM than previously known. Authorities and health professionals' associations need to consider how to prevent further medicalization of the practice. PMID:23444549

  6. Areas Contributing Recharge to Wells in the Tafuna-Leone Plain, Tutuila, American Samoa

    USGS Publications Warehouse

    Izuka, Scot K.; Perreault, Jeff A.; Presley, Todd K.

    2007-01-01

    To address the concerns about the potential for contamination of drinking-water wells in the Tafuna-Leone Plain, Tutuila, American Samoa, a numerical ground-water flow model was developed and used to delineate areas contributing recharge to the wells (ACRWs). Surveys and analyses were conducted to obtain or compile certain essential hydrogeologic information needed for the model, such as groundwater production statistics, ground-water levels under current production, and an assessment of the distribution of groundwater recharge. The ground-water surveys indicate that total production from all wells in the Tafuna-Leone Plain between 1985 and 2005 averaged 6.1 Mgal/d and showed a gradual increase. A synoptic survey indicates that current water levels in the Tafuna-Leone Plain are highest near its inland boundary, decrease toward the coast, and are slightly depressed in high-production well fields. Ground-water levels showed little effect from the increased production because hydraulic conductivites are high and withdrawal is small relative to recharge. Analysis of ground-water recharge using a soil water-budget analysis indicates that the Tafuna-Leone Plain and adjacent areas receive about 280 Mgal/d of water from rainfall, of which 24 percent runs off to the ocean, 26 percent is removed by evapotranspiration, and 50 percent goes to ground-water recharge. Ground-water recharge per unit area is generally higher at the mountain crests than at the coast, but the highest recharge per unit area is in the mountain-front recharge zone at the juncture between the Tafuna-Leone Plain and the adjacent mountains. Surface water from the mountains also contributes to ground-water recharge in the eastern Tafuna-Leone Plain, in a process analogous to mountain-front recharge described in arid areas. Analysis of stream-gage data indicates that in the mountains of Tutuila, ground water discharges and contributes substantially to the total flow of the streams. In contrast, multiple

  7. Inferring Selection Intensity and Allele Age from Multilocus Haplotype Structure

    PubMed Central

    Chen, Hua; Slatkin, Montgomery

    2013-01-01

    It is a challenging task to infer selection intensity and allele age from population genetic data. Here we present a method that can efficiently estimate selection intensity and allele age from the multilocus haplotype structure in the vicinity of a segregating mutant under positive selection. We use a structured-coalescent approach to model the effect of directional selection on the gene genealogies of neutral markers linked to the selected mutant. The frequency trajectory of the selected allele follows the Wright-Fisher model. Given the position of the selected mutant, we propose a simplified multilocus haplotype model that can efficiently model the dynamics of the ancestral haplotypes under the joint influence of selection and recombination. This model approximates the ancestral genealogies of the sample, which reduces the number of states from an exponential function of the number of single-nucleotide polymorphism loci to a quadratic function. That allows parameter inference from data covering DNA regions as large as several hundred kilo-bases. Importance sampling algorithms are adopted to evaluate the probability of a sample by exploring the space of both allele frequency trajectories of the selected mutation and gene genealogies of the linked sites. We demonstrate by simulation that the method can accurately estimate selection intensity for moderate and strong positive selection. We apply the method to a data set of the G6PD gene in an African population and obtain an estimate of 0.0456 (95% confidence interval 0.0144−0.0769) for the selection intensity. The proposed method is novel in jointly modeling the multilocus haplotype pattern caused by recombination and mutation, allowing the analysis of haplotype data in recombining regions. Moreover, the method is applicable to data from populations under exponential growth and a variety of other demographic histories. PMID:23797107

  8. An approach to mapping haplotype-specific recombination sites in human MHC class III

    SciTech Connect

    Levo, A.; Westman, P.; Partanen, J.

    1996-12-31

    Studies of the major histocompatibility complex (MHC) in mouse indicate that the recombination sites are not randomly distributed and their occurrence is haplotype-dependent. No data concerning haplotype-specific recombination sites in human are available due to the low number of informative families. To investigate haplotype-specific recombination sites in human MHC, we describe an approach based on identification of recombinant haplotypes derived from one conserved haplotype at the population level. The recombination sites were mapped by comparing polymorphic markers between the recombinant and assumed original haplotypes. We tested this approach on the extended haplotype HLA A3; B47; Bf{sup *}F; C4A{sup *}1; C4B{sup *}Q0; DR7, which is most suitable for this analysis. First, it carries a number of rare markers, and second, the haplotype, albeit rare in the general population, is frequent in patients with 21-hydroxylase (21OH) defect. We observed recombinants derived from this haplotype in patients with 21OH defect. All these haplotypes had the centromeric part (from Bf to DR) identical to the original haplotype, but they differed in HLA A and B. We therefore assumed that they underwent recombinations in the segment that separates the Bf and HLA B genes. Polymorphic markers indicated that all break points mapped to two segments near the TNF locus. This approach makes possible the mapping of preferential recombination sites in different haplotypes. 20 refs., 1 fig., 1 tab.

  9. Cluster of Ebola Virus Disease Linked to a Single Funeral - Moyamba District, Sierra Leone, 2014.

    PubMed

    Curran, Kathryn G; Gibson, James J; Marke, Dennis; Caulker, Victor; Bomeh, John; Redd, John T; Bunga, Sudhir; Brunkard, Joan; Kilmarx, Peter H

    2016-03-01

    As of February 17, 2016, a total of 14,122 cases (62% confirmed) of Ebola Virus Disease (Ebola) and 3,955 Ebola-related deaths had been reported in Sierra Leone since the epidemic in West Africa began in 2014. A key focus of the Ebola response in Sierra Leone was the promotion and implementation of safe, dignified burials to prevent Ebola transmission by limiting contact with potentially infectious corpses. Traditional funeral practices pose a substantial risk for Ebola transmission through contact with infected bodies, body fluids, contaminated clothing, and other personal items at a time when viral load is high; however, the role of funeral practices in the Sierra Leone epidemic and ongoing Ebola transmission has not been fully characterized. In September 2014, a sudden increase in the number of reported Ebola cases occurred in Moyamba, a rural and previously low-incidence district with a population of approximately 260,000. The Sierra Leone Ministry of Health and Sanitation and CDC investigated and implemented public health interventions to control this cluster of Ebola cases, including community engagement, active surveillance, and close follow-up of contacts. A retrospective analysis of cases that occurred during July 11-October 31, 2014, revealed that 28 persons with confirmed Ebola had attended the funeral of a prominent pharmacist during September 5-7, 2014. Among the 28 attendees with Ebola, 21 (75%) reported touching the man's corpse, and 16 (57%) reported having direct contact with the pharmacist before he died. Immediate, safe, dignified burials by trained teams with appropriate protective equipment are critical to interrupt transmission and control Ebola during times of active community transmission; these measures remain important during the current response phase. PMID:26938950

  10. Porting LEON3FT/GRLIB to 4th Generation Flash-Based Devices

    NASA Astrophysics Data System (ADS)

    Andersson, Jan; Habinc, Sandi; Prinetto, Paolo; Trotta, Pascal

    2015-09-01

    Cobham Gaisler develops the LEON3FT SPARC V8 fault-tolerant microprocessor that is available both as IP cores part of an IP library (GRLIB) that allows users to design their own custom system-on-chip (SoC) designs, and also as part of ready-made designs and devices. Cobham Gaisler has recently added support for Microsemi IGLOO2, and experimental support for Microsemi radiation-tolerant RTG4, devices to GRLIB.

  11. Natural law Judaism? The genesis of bioethics in Hans Jonas, Leo Strauss, and Leon Kass.

    PubMed

    Vogel, Lawrence

    2006-01-01

    Leon Kass is much misunderstood. He is not simply a Republican ideologue who tailored his ideas to break out of the ivory tower and into the halls of power. Nor does he look simply to use human nature as a moral guide. When the full range of his writings is considered and set in the tradition of his teachers, Hans Jonas and Leo Strauss, what emerges is a natural law position colored by religious revelation. PMID:16776021

  12. Transmission dynamics of Ebola virus disease and intervention effectiveness in Sierra Leone

    PubMed Central

    Fang, Li-Qun; Yang, Yang; Jiang, Jia-Fu; Yao, Hong-Wu; Kargbo, David; Li, Xin-Lou; Jiang, Bao-Gui; Kargbo, Brima; Tong, Yi-Gang; Wang, Ya-Wei; Liu, Kun; Kamara, Abdul; Dafae, Foday; Kanu, Alex; Jiang, Rui-Ruo; Sun, Ye; Sun, Ruo-Xi; Chen, Wan-Jun; Ma, Mai-Juan; Dean, Natalie E.; Thomas, Harold; Longini, Ira M.; Halloran, M. Elizabeth; Cao, Wu-Chun

    2016-01-01

    Sierra Leone is the most severely affected country by an unprecedented outbreak of Ebola virus disease (EVD) in West Africa. Although successfully contained, the transmission dynamics of EVD and the impact of interventions in the country remain unclear. We established a database of confirmed and suspected EVD cases from May 2014 to September 2015 in Sierra Leone and mapped the spatiotemporal distribution of cases at the chiefdom level. A Poisson transmission model revealed that the transmissibility at the chiefdom level, estimated as the average number of secondary infections caused by a patient per week, was reduced by 43% [95% confidence interval (CI): 30%, 52%] after October 2014, when the strategic plan of the United Nations Mission for Emergency Ebola Response was initiated, and by 65% (95% CI: 57%, 71%) after the end of December 2014, when 100% case isolation and safe burials were essentially achieved, both compared with before October 2014. Population density, proximity to Ebola treatment centers, cropland coverage, and atmospheric temperature were associated with EVD transmission. The household secondary attack rate (SAR) was estimated to be 0.059 (95% CI: 0.050, 0.070) for the overall outbreak. The household SAR was reduced by 82%, from 0.093 to 0.017, after the nationwide campaign to achieve 100% case isolation and safe burials had been conducted. This study provides a complete overview of the transmission dynamics of the 2014−2015 EVD outbreak in Sierra Leone at both chiefdom and household levels. The interventions implemented in Sierra Leone seem effective in containing the epidemic, particularly in interrupting household transmission. PMID:27035948

  13. Transmission dynamics of Ebola virus disease and intervention effectiveness in Sierra Leone.

    PubMed

    Fang, Li-Qun; Yang, Yang; Jiang, Jia-Fu; Yao, Hong-Wu; Kargbo, David; Li, Xin-Lou; Jiang, Bao-Gui; Kargbo, Brima; Tong, Yi-Gang; Wang, Ya-Wei; Liu, Kun; Kamara, Abdul; Dafae, Foday; Kanu, Alex; Jiang, Rui-Ruo; Sun, Ye; Sun, Ruo-Xi; Chen, Wan-Jun; Ma, Mai-Juan; Dean, Natalie E; Thomas, Harold; Longini, Ira M; Halloran, M Elizabeth; Cao, Wu-Chun

    2016-04-19

    Sierra Leone is the most severely affected country by an unprecedented outbreak of Ebola virus disease (EVD) in West Africa. Although successfully contained, the transmission dynamics of EVD and the impact of interventions in the country remain unclear. We established a database of confirmed and suspected EVD cases from May 2014 to September 2015 in Sierra Leone and mapped the spatiotemporal distribution of cases at the chiefdom level. A Poisson transmission model revealed that the transmissibility at the chiefdom level, estimated as the average number of secondary infections caused by a patient per week, was reduced by 43% [95% confidence interval (CI): 30%, 52%] after October 2014, when the strategic plan of the United Nations Mission for Emergency Ebola Response was initiated, and by 65% (95% CI: 57%, 71%) after the end of December 2014, when 100% case isolation and safe burials were essentially achieved, both compared with before October 2014. Population density, proximity to Ebola treatment centers, cropland coverage, and atmospheric temperature were associated with EVD transmission. The household secondary attack rate (SAR) was estimated to be 0.059 (95% CI: 0.050, 0.070) for the overall outbreak. The household SAR was reduced by 82%, from 0.093 to 0.017, after the nationwide campaign to achieve 100% case isolation and safe burials had been conducted. This study provides a complete overview of the transmission dynamics of the 2014-2015 EVD outbreak in Sierra Leone at both chiefdom and household levels. The interventions implemented in Sierra Leone seem effective in containing the epidemic, particularly in interrupting household transmission. PMID:27035948

  14. Chinese military medical teams in the Ebola outbreak of Sierra Leone.

    PubMed

    Lu, Yinying; Rong, G; Yu, S P; Sun, Z; Duan, X; Dong, Z; Xia, H; Zhan, N; Jin, C; Ji, J; Duan, H

    2016-06-01

    The 2014-2015 Ebola virus disease (EVD) epidemic in West Africa was the largest in history. The three most affected countries, Guinea, Liberia and Sierra Leone, have faced enormous challenges in controlling transmission and providing clinical care for patients with EVD. The Chinese government, in response to the requests of the WHO and the governments of the affected countries, responded rapidly by deploying Chinese military medical teams (CMMTs) to the areas struck by the deadly epidemic. A total of three CMMTs, comprising 115 military medical professionals, were rotationally deployed to Freetown, Sierra Leone to assist with infection prevention and control, clinical care and health promotion and training. Between 1 October 2014 and 22 March 2015, the CMMTs in Sierra Leone admitted and treated a total of 773 suspected and 285 confirmed EVD cases. Among the 285 confirmed cases, 146 (51.2%) patients survived after treatment. In addition, the CMMTs maintained the record of zero infections among healthcare workers and zero cross-infections between quarantined patients. In this manuscript, we aim to give an overview of the mission, and share our best practices experience on predeployment preparedness, EVD holding and treatment centre building and EVD case management. PMID:26744190

  15. Analysis of water-surface profiles in Leon County and the city of Tallahassee, Florida

    USGS Publications Warehouse

    Franklin, M.A.; Orr, R.A.

    1987-01-01

    Water surface profiles for the 10-, 25-, 50-, and 100-yr recurrence interval floods for most of the streams that drain developing areas of Leon County and the city of Tallahassee are presented. The principal streams studied are in the Lake Munson, Lake Lafayette, and Lake Jackson basins Peak discharges were computed from regression equations based on information gained from 15 streamflow stations in the area. Standard step-backwater procedures were used to determine the water-surface elevations for the streams. The flood elevations were generally higher than those in the Flood Insurance Studies for Tallahassee (1976) and Leon County (1982). The primary reason for the higher profiles is that peak discharges used in this report are larger than those used previously, largely due to changes in land use. The flood profiles for Bradford Brook, North Branch Gum Creek, and West Branch Gum Creek generally match those in the Leon County Flood Insurance Studies. Channel improvements in some areas would lower the flood elevation in that area, but would probably increase flooding downstream. (Lantz-PTT)

  16. Learning from the challenges of Ebola Virus Disease contact tracers in Sierra Leone, February, 2015

    PubMed Central

    Ilesanmi, Olayinka Stephen

    2015-01-01

    Introduction Sierra Leone was in the process of strengthening tracing of Ebola Virus Disease (EVD) contact with training of contact tracers, continuous mentoring and monitoring, supervision and continuous support. This was through various national and international organizations. This study aimed at identifying the challenges of contact tracers with a view of improving contact tracing activities in Tonkolili District, Sierra Leone. Methods In-depth interview was conducted among contact tracers who were actively involved in contact tracing within the 4 weeks preceding the interview. In-depth interview guide was used to interview the contact tracers. Questions were asked about the state of EVD outbreak, challenges of contact tracing, ways to improving contact tracers activities and ways to ensure community participation and follow up action. Results A total of 12 Contact tracers were interviewed. Most of the contact tracers saw the lifting of ban by the Government on movement as a delay to stopping the outbreak. Some of them were being threatened by their communities and insulted. Some communities with EVD cases felt it was no longer in Sierra Leone and that the contact tracers were the ones infecting the people with Ebola. More than 80% of the participants indicated that retraining of contact tracers and re-orientation of community members would help in putting a stop to the outbreak. Conclusion All participants indicated interest in improving their activities and performance. They suggested that more social mobilization is needed to ensure the cooperation of their communities. PMID:26740849

  17. Chinese military medical teams in the Ebola outbreak of Sierra Leone

    PubMed Central

    Lu, Yinying; Rong, G; Yu, S P; Sun, Z; Duan, X; Dong, Z; Xia, H; Zhan, N; Jin, C; Ji, J; Duan, H

    2016-01-01

    The 2014–2015 Ebola virus disease (EVD) epidemic in West Africa was the largest in history. The three most affected countries, Guinea, Liberia and Sierra Leone, have faced enormous challenges in controlling transmission and providing clinical care for patients with EVD. The Chinese government, in response to the requests of the WHO and the governments of the affected countries, responded rapidly by deploying Chinese military medical teams (CMMTs) to the areas struck by the deadly epidemic. A total of three CMMTs, comprising 115 military medical professionals, were rotationally deployed to Freetown, Sierra Leone to assist with infection prevention and control, clinical care and health promotion and training. Between 1 October 2014 and 22 March 2015, the CMMTs in Sierra Leone admitted and treated a total of 773 suspected and 285 confirmed EVD cases. Among the 285 confirmed cases, 146 (51.2%) patients survived after treatment. In addition, the CMMTs maintained the record of zero infections among healthcare workers and zero cross-infections between quarantined patients. In this manuscript, we aim to give an overview of the mission, and share our best practices experience on predeployment preparedness, EVD holding and treatment centre building and EVD case management. PMID:26744190

  18. How Have Self-Incompatibility Haplotypes Diversified? Generation of New Haplotypes during the Evolution of Self-Incompatibility from Self-Compatibility.

    PubMed

    Sakai, Satoki

    2016-08-01

    I developed a gametophytic self-incompatibility (SI) model to study the conditions leading to diversification in SI haplotypes. In the model, the SI system is assumed to be incomplete, and the pollen expressing a given specificity is not fully rejected by the pistils expressing the same specificity. I also assumed that mutations can occur that enhance the rejection of pollen by pistils with the same haplotype variant and reduce rejection by pistils with other variants in the same haplotype. I found that if such mutations occur, the new haplotypes (mutant variants) can stably coexist with the ancestral haplotype in which the mutant arose. This is because pollen bearing the new haplotype is most strongly rejected by pistils bearing the same new haplotype among the pistils in the population; hence, negative frequency-dependent selection prevents their fixation. I also performed simulations and found that the nearly complete SI system evolves from completely self-compatible populations and that SI haplotypes can increase to about 40-50 within a few thousand generations. On the basis of my findings, I propose that diversification of SI haplotypes occurred during the evolution of SI from self-compatibility. PMID:27420782

  19. Age-dependent pharmacokinetic and pharmacodynamic response in preweanling rats following oral exposure to the organophosphorus insecticide chlorpyrifos

    SciTech Connect

    Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.

    2006-03-01

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to CPF-oxon and 3,5,6-trichloro-2-pyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. The pharmacokinetics of CPF, TCP, and the extent of blood (plasma/RBC), and brain ChE inhibition in rats were determined on postnatal days (PND) -5, -12, and -17 following oral gavage administration of 1 and 10 mg CPF/kg of body weight. For all neonatal ages the blood TCP exceeded the CPF concentration, and within each age group there was no evidence of non-linear kinetics over the dose range evaluated. Younger animals demonstrated a greater sensitivity to ChE inhibition as evident by the dose- and age-dependent inhibition of plasma, RBC, and brain ChE. Of particular importance was the observation that even in rats as young as PND-5, the CYP450 metabolic capacity was adequate to metabolize CPF to both TCP and CPF-oxon based on the detection of TCP in blood and extensive ChE inhibition (biomarker of CPF-oxon) at all ages. In addition, the increase in the blood TCP concentration ({approx}3-fold) in PND-17 rats relative to the response in the younger animals, and the higher blood concentrations of CPF in neonatal rats (1.7 to 7.5-fold) relative to adults was consistent with an increase in CYP450 metabolic capacity with age. This is the first reported study that evaluated both the pharmacokinetics of the parent pesticide, the major metabolite and the extent of ChE inhibition dynamics in the same animals as a function of neonatal age. The results suggest that in the neonatal rat, CPF was rapidly absorbed and metabolized, and the extent of metabolism was age-dependent.

  20. Introduced and Native Haplotypes of Echinococcus multilocularis in Wildlife in Saskatchewan, Canada.

    PubMed

    Gesy, Karen M; Jenkins, Emily J

    2015-07-01

    Recent detection of a European-type haplotype of the cestode Echinococcus multilocularis in a newly enzootic region in British Columbia prompted efforts to determine if this haplotype was present elsewhere in wildlife in western Canada. In coyote (Canis latrans) definitive hosts in an urban region in central Saskatchewan (SK), we found a single haplotype of E. multilocularis that was most similar to a haplotype currently established in the core of this parasite's distribution in Europe and to the European-type haplotype found in coyotes and a dog (Canis lupus familiaris) in British Columbia. We found six haplotypes of E. multilocularis from deer mouse (Peromyscus maniculatus) intermediate hosts in southwestern SK that were closely related to, and one haplotype indistinguishable from, a haplotype previously reported in the adjacent north-central US. This is a higher level of diversity than has previously been recognized for this parasite, which suggests that the population native to central North America is well established, rather than a recent introduction from the Arctic. These findings, in combination with recent cases of alveolar hydatid cysts in dogs in Canada, raise concerns that European haplotypes of E. multilocularis may be increasing in distribution within wildlife in Canada. European haplotypes may pose greater risks to veterinary and human health than native haplotypes long established in central North America. PMID:26020284

  1. Integrative analysis of haplotype-resolved epigenomes across human tissues.

    PubMed

    Leung, Danny; Jung, Inkyung; Rajagopal, Nisha; Schmitt, Anthony; Selvaraj, Siddarth; Lee, Ah Young; Yen, Chia-An; Lin, Shin; Lin, Yiing; Qiu, Yunjiang; Xie, Wei; Yue, Feng; Hariharan, Manoj; Ray, Pradipta; Kuan, Samantha; Edsall, Lee; Yang, Hongbo; Chi, Neil C; Zhang, Michael Q; Ecker, Joseph R; Ren, Bing

    2015-02-19

    Allelic differences between the two homologous chromosomes can affect the propensity of inheritance in humans; however, the extent of such differences in the human genome has yet to be fully explored. Here we delineate allelic chromatin modifications and transcriptomes among a broad set of human tissues, enabled by a chromosome-spanning haplotype reconstruction strategy. The resulting large collection of haplotype-resolved epigenomic maps reveals extensive allelic biases in both chromatin state and transcription, which show considerable variation across tissues and between individuals, and allow us to investigate cis-regulatory relationships between genes and their control sequences. Analyses of histone modification maps also uncover intriguing characteristics of cis-regulatory elements and tissue-restricted activities of repetitive elements. The rich data sets described here will enhance our understanding of the mechanisms by which cis-regulatory elements control gene expression programs. PMID:25693566

  2. Integrative analysis of haplotype-resolved epigenomes across human tissues

    PubMed Central

    Schmitt, Anthony; Selvaraj, Siddarth; Lee, Ah Young; Yen, Chia-An; Lin, Shin; Lin, Yiing; Qiu, Yunjiang; Xie, Wei; Yue, Feng; Hariharan, Manoj; Ray, Pradipta; Kuan, Samantha; Edsall, Lee; Yang, Hongbo; Chi, Neil C.; Zhang, Michael Q.; Ecker, Joseph R.; Ren, Bing

    2015-01-01

    Allelic differences between the two homologous chromosomes can affect the propensity of inheritance in humans; however, the extent of such differences in the human genome has yet to be fully explored. Here, for the first time, we delineate allelic chromatin modifications and transcriptomes amongst a broad set of human tissues, enabled by a chromosome-spanning haplotype reconstruction strategy1. The resulting masses of haplotype-resolved epigenomic maps reveal extensive allelic biases in both chromatin state and transcription, which show considerable variation across tissues and between individuals, and allow us to investigate cis-regulatory relationships between genes and their control sequences. Analyses of histone modification maps also uncover intriguing characteristics of cis-regulatory elements and tissue-restricted activities of repetitive elements. The rich datasets described here will enhance our understanding of the mechanisms of how cis-regulatory elements control gene expression programs. PMID:25693566

  3. RCAN1 overexpression promotes age-dependent mitochondrial dysregulation related to neurodegeneration in Alzheimer’s disease

    PubMed Central

    Wong, Helen; Levenga, Josien; Cain, Peter; Rothermel, Beverly; Klann, Eric

    2016-01-01

    Aging is the largest risk factor for Alzheimer’s disease (AD). Patients with Down syndrome (DS) develop symptoms consistent with early-onset AD, suggesting that overexpression of chromosome 21 genes such as Regulator of Calcineurin 1 (RCAN1) plays a role in AD pathogenesis. RCAN1 levels are increased in the brain of DS and AD patients but also in the human brain with normal aging. RCAN1 has been implicated in several neuronal functions, but whether its increased expression is correlative or causal in the aging-related progression of AD remains elusive. We show that brain-specific overexpression of the human RCAN1.1S isoform in mice promotes early age-dependent memory and synaptic plasticity deficits, tau pathology, and dysregulation of dynamin-related protein 1 (DRP1) activity associated with mitochondrial dysfunction and oxidative stress, reproducing key AD features. Based on these findings, we propose that chronic RCAN1 overexpression during aging alters DRP1-mediated mitochondrial fission and thus acts to promote AD-related progressive neurodegeneration. PMID:26497675

  4. Slow age-dependent decline of doublecortin expression and BrdU labeling in the forebrain from lesser hedgehog tenrecs.

    PubMed

    Alpár, Alán; Künzle, Heinz; Gärtner, Ulrich; Popkova, Yulia; Bauer, Ute; Grosche, Jens; Reichenbach, Andreas; Härtig, Wolfgang

    2010-05-12

    In addition to synaptic remodeling, formation of new neurons is increasingly acknowledged as an important cue for plastic changes in the central nervous system. Whereas all vertebrates retain a moderate neuroproliferative capacity, phylogenetically younger mammals become dramatically impaired in this potential during aging. The present study shows that the lesser hedgehog tenrec, an insectivore with a low encephalization index, preserves its neurogenic potential surprisingly well during aging. This was shown by quantitative analysis of 5-bromo-2'-deoxyuridine (BrdU) immunolabeling in the olfactory bulb, paleo-, archi-, and neocortices from 2- to 7-year-old animals. In addition to these newly born cells, a large number of previously formed immature neurons are present throughout adulthood as shown by doublecortin (DCX) immunostaining in various forebrain regions including archicortex, paleocortex, nucleus accumbens, and amygdala. Several ventricle-associated cells in olfactory bulb and hippocampus were double-labeled by BrdU and DCX immunoreactivity. However, most DCX cells in the paleocortex can be considered as persisting immature neurons that obviously do not enter a differentiation program since double fluorescence labeling does not reveal their co-occurrence with numerous neuronal markers, whereas only a small portion coexpresses the pan-neuronal marker HuC/D. Finally, the present study reveals tenrecs as suitable laboratory animals to study age-dependent brain alterations (e.g., of neurogenesis) or slow degenerative processes, particularly due to the at least doubled longevity of tenrecs in comparison to mice and rats. PMID:20298680

  5. Age-Dependent Morphologic Alterations in the Outer Retinal and Choroidal Thicknesses Using Swept Source Optical Coherence Tomography

    PubMed Central

    2016-01-01

    Purpose To evaluate the age-dependent morphologic alterations in the outer retina and choroid at the macula using swept-source optical coherence tomography (OCT). Methods Thirty eyes (30 normal subjects; average age, 49 years) were examined; five (age range, third-eighth decades of life) had refractive errors of ±2 diopters or less and no fundus abnormalities. An Early Treatment Diabetic Retinopathy Study (ETDRS) map of the outer retinal and choroidal thickness was constructed using swept-source OCT. The outer retinal and choroidal segmentation lines were drawn automatically, partially manually, within 6 millimeters of the macula. Results The mean outer retinal and choroidal thicknesses in the 6-millimeter-diameter circle were 145±13 and 236±68 microns, respectively. The choroidal thickness and age were negatively (r = -0.66, P<0.01) correlated; the outer retinal thickness and age were not correlated (r = -0.16, P = 0.39). The outer retinal and choroidal thicknesses in the ETDRS map were not correlated (r = -0.13, P = 0.49) within 1 millimeter but correlated (r = 0.32, P<0.01) within 6 millimeters. Conclusions The choroid thins with aging. The outer retina remains stable. Outer retina and choroid are correlated in the entire macula except for the center. ETDRS map can be useful for evaluation of the morphologic relationship between the outer retina and choroid. PMID:27467879

  6. Conversion coefficients for age-dependent ORNL phantoms from 137Cs in soil as a source of external exposure

    NASA Astrophysics Data System (ADS)

    Krstic, D.; Nikezic, D.

    2007-09-01

    Dose conversion coefficients for different organs of age-dependent ORNL phantoms, due to the 137Cs in soil have been calculated using the MCNP-4B code. A cylindrical source at a depth of 20 cm was subdivided into 10 smaller cylinders, each of height 2 cm. Any one of these smaller cylinders could be considered as a source of photons with the energies of 661.6 keV. The ORNL phantoms stand exactly above the center of the cylinders. MCNP-4B energy deposition tally (F6) in MeV/g per one emitted photon was used to calculate absorbed doses in organs of phantoms. Then, conversion of units was made to obtain absorbed dose in fGy (femto-Gray) per Bq s kg -1. Absorbed doses in all major organs and the remainder, defined in reports ICRP60 and 74, were calculated as a function of the 137Cs source depth. Conversion coefficients decrease as the phantom age increases.

  7. Rapamycin activates autophagy in Hutchinson-Gilford progeria syndrome: implications for normal aging and age-dependent neurodegenerative disorders.

    PubMed

    Graziotto, John J; Cao, Kan; Collins, Francis S; Krainc, Dimitri

    2012-01-01

    While rapamycin has been in use for years in transplant patients as an antirejection drug, more recently it has shown promise in treating diseases of aging, such as neurodegenerative disorders and atherosclerosis. We recently reported that rapamycin reverses the cellular phenotype of fibroblasts from children with the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). We found that the causative aberrant protein, progerin, was cleared through autophagic mechanisms when the cells were treated with rapamycin, suggesting a new potential treatment for HGPS. Recent evidence shows that progerin is also present in aged tissues of healthy individuals, suggesting that progerin may contribute to physiological aging. While it is intriguing to speculate that rapamycin may affect normal aging in humans, as it does in lower organisms, it will be important to identify safer analogues of rapamycin for chronic treatments in humans in order to minimize toxicity. In addition to its role in HGPS and normal aging, we discuss the potential of rapamycin for the treatment of age-dependent neurodegenerative diseases. PMID:22170152

  8. Expression of A152T human tau causes age-dependent neuronal dysfunction and loss in transgenic mice.

    PubMed

    Maeda, Sumihiro; Djukic, Biljana; Taneja, Praveen; Yu, Gui-Qiu; Lo, Iris; Davis, Allyson; Craft, Ryan; Guo, Weikun; Wang, Xin; Kim, Daniel; Ponnusamy, Ravikumar; Gill, T Michael; Masliah, Eliezer; Mucke, Lennart

    2016-04-01

    A152T-variant human tau (hTau-A152T) increases risk for tauopathies, including Alzheimer's disease. Comparing mice with regulatable expression of hTau-A152T or wild-type hTau (hTau-WT), we find age-dependent neuronal loss, cognitive impairments, and spontaneous nonconvulsive epileptiform activity primarily in hTau-A152T mice. However, overexpression of either hTau species enhances neuronal responses to electrical stimulation of synaptic inputs and to an epileptogenic chemical. hTau-A152T mice have higher hTau protein/mRNA ratios in brain, suggesting that A152T increases production or decreases clearance of hTau protein. Despite their functional abnormalities, aging hTau-A152T mice show no evidence for accumulation of insoluble tau aggregates, suggesting that their dysfunctions are caused by soluble tau. In human amyloid precursor protein (hAPP) transgenic mice, co-expression of hTau-A152T enhances risk of early death and epileptic activity, suggesting copathogenic interactions between hTau-A152T and amyloid-β peptides or other hAPP metabolites. Thus, the A152T substitution may augment risk for neurodegenerative diseases by increasing hTau protein levels, promoting network hyperexcitability, and synergizing with the adverse effects of other pathogenic factors. PMID:26931567

  9. Cerebrospinal Fluid Extracellular Vesicles Undergo Age Dependent Declines and Contain Known and Novel Non-coding RNAs

    PubMed Central

    Tietje, Ashlee; Maron, Kourtney N.; Wei, Yanzhang; Feliciano, David M.

    2014-01-01

    Brain development requires precise orchestration of cellular events through the coordinate exchange of information between distally located cells. One mechanism by which intercellular communication is achieved is through the transfer of extracellular vesicles (EVs). Exosomes are EVs that carry lipids, nucleic acids, and proteins and are detectable in most biological fluids including cerebrospinal fluid (CSF). Here we report that CSF EV concentrations undergo age dependent fluctuations. We characterized EV RNA content by next generation small RNA sequencing and miRNA microarray analysis and identified a temporal shift in CSF EV content. CSF EVs encapsulated miRNAs that contain a conserved hnRNPA2/B1 recognition sequence. We found that hnRNPA2/B1-containing EVs were produced by choroid plexus epithelial cells and that hnRNPA2/B1 containing EVs decreased with age. These results provide insight into EV exchange of miRNAs within the central nervous system and a framework to understand how changes in EVs may have an important impact on brain development. PMID:25420022

  10. Survival Prediction Score: A Simple but Age-Dependent Method Predicting Prognosis in Patients Undergoing Palliative Radiotherapy

    PubMed Central

    Dalhaug, Astrid; Pawinski, Adam; Haukland, Ellinor

    2014-01-01

    Purpose. Validation of a Canadian three-tiered prognostic model (survival prediction score, SPS) in Norwegian cancer patients referred for palliative radiotherapy (PRT), and evaluation of age-dependent performance of the model. Patients and Methods. We analyzed all 579 PRT courses administered at a dedicated PRT facility between 20.06.07 and 31.12.2009. SPS was assigned as originally described, That is, by taking into consideration three variables: primary cancer type, site of metastases, and performance status. Results. Patients with poor prognosis (non-breast cancer, metastases other than bone, and Karnofsky performance status (KPS) ≤ 60) had median survival of 13 weeks. Those with intermediate prognosis (two of these parameters) survived for a median of 29 weeks, and patients with good prognosis for a median of 114 weeks, P < 0.001. While this model performed well in patients who were 60 years or older, it was less satisfactory in younger patients (no significant difference between the good and intermediate prognosis groups). Conclusion. SPS should mainly be used to predict survival of elderly cancer patients. However, even in this group accuracy is limited because the good prognosis group contained patients with short survival, while the poor prognosis group contained long-term survivors. Thus, improved models should be developed. PMID:25006508

  11. Apolipoprotein E4 Causes Age-Dependent Disruption of Slow Gamma Oscillations during Hippocampal Sharp-Wave Ripples.

    PubMed

    Gillespie, Anna K; Jones, Emily A; Lin, Yuan-Hung; Karlsson, Mattias P; Kay, Kenneth; Yoon, Seo Yeon; Tong, Leslie M; Nova, Philip; Carr, Jessie S; Frank, Loren M; Huang, Yadong

    2016-05-18

    Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer's disease (AD), but the mechanism by which it causes cognitive decline is unclear. In knockin (KI) mice, human apoE4 causes age-dependent learning and memory impairments and degeneration of GABAergic interneurons in the hippocampal dentate gyrus. Here we report two functional apoE4-KI phenotypes involving sharp-wave ripples (SWRs), hippocampal network events critical for memory processes. Aged apoE4-KI mice had fewer SWRs than apoE3-KI mice and significantly reduced slow gamma activity during SWRs. Elimination of apoE4 in GABAergic interneurons, which prevents learning and memory impairments, rescued SWR-associated slow gamma activity but not SWR abundance in aged mice. SWR abundance was reduced similarly in young and aged apoE4-KI mice; however, the full SWR-associated slow gamma deficit emerged only in aged apoE4-KI mice. These results suggest that progressive decline of interneuron-enabled slow gamma activity during SWRs critically contributes to apoE4-mediated learning and memory impairments. VIDEO ABSTRACT. PMID:27161522

  12. [Age-dependent changes of morphometric and histochemical characteristics of neurocytes in different ganglia of albino rats].

    PubMed

    Rumiantseva, T A

    2004-01-01

    The aim of this study was to obtain the normative data on the age-dependent transformation of morphometric and histochemical characteristics of neurocytes in different ganglia in albino rats. Cell cross-sectional area, activities of cholinesterase (demonstrated with thioacetic acid method) monoamine oxidase (demonstrated with Glenner method) were measured in neurocytes of stellate, spinal, trigeminal and gastric ganglia in rats aged 2 to 360 days. Measurements were made with the help of "Bioscan" videoanalyzer. Informational analysis was used for the evaluation of the degree of maturation of neurocyte systems. General features, age- and organ-related peculiarities of morphometric and enzyme-histochemical characteristics were established for neurocytes of different ganglia, as well as a heterochronism of their definitive state attainment. The time of stabilization for neurocytes of stellate and I thoracic spinal ganglia was the age of 60 days, for those of trigeminal ganglion and intramural gastric ganglia -90 and 120 days, respectively. By this time, neurocyte systems turned from a determined state into a probabilistic-determined one, this transformation being considered as a population stabilization. PMID:15359692

  13. Cerebrospinal fluid extracellular vesicles undergo age dependent declines and contain known and novel non-coding RNAs.

    PubMed

    Tietje, Ashlee; Maron, Kourtney N; Wei, Yanzhang; Feliciano, David M

    2014-01-01

    Brain development requires precise orchestration of cellular events through the coordinate exchange of information between distally located cells. One mechanism by which intercellular communication is achieved is through the transfer of extracellular vesicles (EVs). Exosomes are EVs that carry lipids, nucleic acids, and proteins and are detectable in most biological fluids including cerebrospinal fluid (CSF). Here we report that CSF EV concentrations undergo age dependent fluctuations. We characterized EV RNA content by next generation small RNA sequencing and miRNA microarray analysis and identified a temporal shift in CSF EV content. CSF EVs encapsulated miRNAs that contain a conserved hnRNPA2/B1 recognition sequence. We found that hnRNPA2/B1-containing EVs were produced by choroid plexus epithelial cells and that hnRNPA2/B1 containing EVs decreased with age. These results provide insight into EV exchange of miRNAs within the central nervous system and a framework to understand how changes in EVs may have an important impact on brain development. PMID:25420022

  14. Age-dependent change of HMGB1 and DNA double-strand break accumulation in mouse brain

    SciTech Connect

    Enokido, Yasushi; Yoshitake, Ayaka; Ito, Hikaru; Okazawa, Hitoshi

    2008-11-07

    HMGB1 is an evolutionarily conserved non-histone chromatin-associated protein with key roles in maintenance of nuclear homeostasis; however, the function of HMGB1 in the brain remains largely unknown. Recently, we found that the reduction of nuclear HMGB1 protein level in the nucleus associates with DNA double-strand break (DDSB)-mediated neuronal damage in Huntington's disease [M.L. Qi, K. Tagawa, Y. Enokido, N. Yoshimura, Y. Wada, K. Watase, S. Ishiura, I. Kanazawa, J. Botas, M. Saitoe, E.E. Wanker, H. Okazawa, Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases, Nat. Cell Biol. 9 (2007) 402-414]. In this study, we analyze the region- and cell type-specific changes of HMGB1 and DDSB accumulation during the aging of mouse brain. HMGB1 is localized in the nuclei of neurons and astrocytes, and the protein level changes in various brain regions age-dependently. HMGB1 reduces in neurons, whereas it increases in astrocytes during aging. In contrast, DDSB remarkably accumulates in neurons, but it does not change significantly in astrocytes during aging. These results indicate that HMGB1 expression during aging is differentially regulated between neurons and astrocytes, and suggest that the reduction of nuclear HMGB1 might be causative for DDSB in neurons of the aged brain.

  15. Life-history differences in age-dependent expressions of multiple ornaments and behaviors in a lekking bird.

    PubMed

    Kervinen, Matti; Lebigre, Christophe; Alatalo, Rauno V; Siitari, Heli; Soulsbury, Carl D

    2015-01-01

    Age is a major factor explaining variation in life-history traits among individuals with typical patterns of increasing trait values early in life, maximum trait expression, and senescence. However, age-dependent variation in the expressions of sexually selected traits has received less attention, although such variation underpins differences in male competitive abilities and female preference, which are central to sexual selection. In contrast to previous studies focusing on single traits, we used repeated measures of seven sexually selected morphological and behavioral traits in male black grouse (Tetrao tetrix) to quantify the effects of age and life span on their expressions and quantified this variation in relation to male reproductive effort. Trait expression increased with age, but long-lived males had a slower increase and delayed maxima in trait values compared with short-lived males. There was evidence of terminal investment (increasing trait values during the last breeding season) in some traits and senescence in all traits. These trait dynamics were largely explained by the timing of male peak lekking effort. This study shows that fully understanding the variation in sexually selected traits and fitness benefits associated with sexual selection requires accounting for the complex interaction among individual age, life span, and the timing of individuals' investment in reproduction. PMID:25560550

  16. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

    PubMed Central

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-01-01

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

  17. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment.

    PubMed

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-01-01

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

  18. An MCMC algorithm for haplotype assembly from whole-genome sequence data

    PubMed Central

    Bansal, Vikas; Halpern, Aaron L.; Axelrod, Nelson; Bafna, Vineet

    2008-01-01

    In comparison to genotypes, knowledge about haplotypes (the combination of alleles present on a single chromosome) is much more useful for whole-genome association studies and for making inferences about human evolutionary history. Haplotypes are typically inferred from population genotype data using computational methods. Whole-genome sequence data represent a promising resource for constructing haplotypes spanning hundreds of kilobases for an individual. In this article, we propose a Markov chain Monte Carlo (MCMC) algorithm, HASH (haplotype assembly for single human), for assembling haplotypes from sequenced DNA fragments that have been mapped to a reference genome assembly. The transitions of the Markov chain are generated using min-cut computations on graphs derived from the sequenced fragments. We have applied our method to infer haplotypes using whole-genome shotgun sequence data from a recently sequenced human individual. The high sequence coverage and presence of mate pairs result in fairly long haplotypes (N50 length ∼ 350 kb). Based on comparison of the sequenced fragments against the individual haplotypes, we demonstrate that the haplotypes for this individual inferred using HASH are significantly more accurate than the haplotypes estimated using a previously proposed greedy heuristic and a simple MCMC method. Using haplotypes from the HapMap project, we estimate the switch error rate of the haplotypes inferred using HASH to be quite low, ∼1.1%. Our Markov chain Monte Carlo algorithm represents a general framework for haplotype assembly that can be applied to sequence data generated by other sequencing technologies. The code implementing the methods and the phased individual haplotypes can be downloaded from http://www.cse.ucsd.edu/users/vibansal/HASH/. PMID:18676820

  19. Haplotype inference from unphased SNP data in heterozygous polyploids based on SAT

    PubMed Central

    Neigenfind, Jost; Gyetvai, Gabor; Basekow, Rico; Diehl, Svenja; Achenbach, Ute; Gebhardt, Christiane; Selbig, Joachim; Kersten, Birgit

    2008-01-01

    Background Haplotype inference based on unphased SNP markers is an important task in population genetics. Although there are different approaches to the inference of haplotypes in diploid species, the existing software is not suitable for inferring haplotypes from unphased SNP data in polyploid species, such as the cultivated potato (Solanum tuberosum). Potato species are tetraploid and highly heterozygous. Results Here we present the software SATlotyper which is able to handle polyploid and polyallelic data. SATlo-typer uses the Boolean satisfiability problem to formulate Haplotype Inference by Pure Parsimony. The software excludes existing haplotype inferences, thus allowing for calculation of alternative inferences. As it is not known which of the multiple haplotype inferences are best supported by the given unphased data set, we use a bootstrapping procedure that allows for scoring of alternative inferences. Finally, by means of the bootstrapping scores, it is possible to optimise the phased genotypes belonging to a given haplotype inference. The program is evaluated with simulated and experimental SNP data generated for heterozygous tetraploid populations of potato. We show that, instead of taking the first haplotype inference reported by the program, we can significantly improve the quality of the final result by applying additional methods that include scoring of the alternative haplotype inferences and genotype optimisation. For a sub-population of nineteen individuals, the predicted results computed by SATlotyper were directly compared with results obtained by experimental haplotype inference via sequencing of cloned amplicons. Prediction and experiment gave similar results regarding the inferred haplotypes and phased genotypes. Conclusion Our results suggest that Haplotype Inference by Pure Parsimony can be solved efficiently by the SAT approach, even for data sets of unphased SNP from heterozygous polyploids. SATlotyper is freeware and is distributed as

  20. Phenotypic and genetic effects of recessive haplotypes on yield, longevity, and fertility.

    PubMed

    Cole, J B; Null, D J; VanRaden, P M

    2016-09-01

    Phenotypes from the August 2015 US national genetic evaluation were used to compute phenotypic effects of 18 recessive haplotypes in Ayrshire (n=1), Brown Swiss (n=5), Holstein (n=10), and Jersey (n=2) cattle on milk, fat, and protein yields, somatic cell score (SCS), single-trait productive life (PL), daughter pregnancy rate (DPR), heifer conception rate (HCR), and cow conception rate (CCR). The haplotypes evaluated were Ayrshire haplotype 1, Brown Swiss haplotypes 1 and 2, spinal dysmyelination, spinal muscular atrophy, Weaver Syndrome, brachyspina, Holstein cholesterol deficiency, Holstein haplotypes 1 to 5, bovine leukocyte adhesion deficiency, complex vertebral malformation, mulefoot (syndactyly), and Jersey haplotypes 1 and 2. When causal variants are unknown and tests are based only on single nucleotide polymorphism haplotypes, it can sometimes be difficult to accurately determine carrier status. For example, 2 Holstein haplotypes for cholesterol deficiency have the same single nucleotide polymorphism genotype, but only one of them carries the causative mutation. Genotyped daughters of carrier bulls included in the analysis ranged from 8 for Weaver Syndrome to 17,869 for Holstein haplotype 3. Lactation records preadjusted for nongenetic factors and direct genomic values (DGV) were used to estimate phenotypic and genetic effects of recessive haplotypes, respectively. We found no phenotypic or genetic differences between carriers and noncarriers of Ayrshire or Brown Swiss defects. Several associations were noted for Holstein haplotypes, including fat and HCR for Holstein haplotype 0 carriers; milk, protein, SCS, PL, and fertility for Holstein haplotype 1; protein, PL, CCR, and HCR for Holstein haplotype 2; milk, protein, and fertility for Holstein haplotype 4; and protein yield and DPR for Holstein haplotype 5. There were no differences among bovine leukocyte adhesion deficiency carriers, but complex vertebral malformation affected fat yield and mulefoot

  1. Heterotic Haplotype Capture: precision breeding for hybrid performance.

    PubMed

    Snowdon, Rod J; Abbadi, Amine; Kox, Tobias; Schmutzer, Thomas; Leckband, Gunhild

    2015-07-01

    The need to improve hybrid performance, abiotic stress tolerance, and disease resistance without compromising seed quality makes the targeted capture of untapped diversity a major objective for crop breeders. Here we introduce the concept of Heterotic Haplotype Capture (HHC), in which genome sequence imputation is used to trace novel heterozygous chromosome blocks contributing to hybrid performance in large, structured populations of interrelated F1 hybrids containing interesting new diversity for breeding. PMID:26027461

  2. Extended HLA-D region haplotype associated with celiac disease

    SciTech Connect

    Howell, M.D.; Smith, J.R.; Austin, R.K.; Kelleher, D.; Nepom, G.T.; Volk, B.; Kagnoff, M.F.

    1988-01-01

    Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. The authors previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II ..beta..-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. They now report the isolation of this ..beta..-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP ..beta..-chain. This celiac disease-associated HLA-DP ..beta..-chain gene was flanked by HLA-DP ..cap alpha..-chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DP..cap alpha..-chain genes of celiac disease patients also were studied by RFLP analysis. Celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP ..cap alpha..- and ..beta..-chain gene RFLPs. Within the celiac-disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion.

  3. MHC haplotype involvement in avian resistance to an ectoparasite.

    PubMed

    Owen, Jeb P; Delany, Mary E; Mullens, Bradley A

    2008-10-01

    Research on immune function in evolutionary ecology has frequently focused on avian ectoparasites (e.g., mites and lice). However, host immunogenetics involved with bird resistance to ectoparasites has not been determined. The critical role of the major histocompatibility complex (MHC) in adaptive immunity and high genetic variation found within the MHC make this gene complex useful for exploring the immunogenetic basis for bird resistance to ectoparasites. The objective of this study was to determine if the avian MHC influenced resistance to a blood-feeding ectoparasite. Four congenic lines of chickens, differing only at the MHC, were comparatively infested with a cosmopolitan ectoparasite of birds-northern fowl mite (NFM)-which is also a serious pest species of poultry. Mite infestations were monitored over time and mite densities (weekly and maximum) were compared among lines. Chickens with the MHC haplotype B21 were relatively resistant to NFM, compared with birds in the B15 congenic line (P < 0.02). To test for similar effects in an outbred genetic background, a separate experiment was performed with 107 commercial chickens (white leghorn, W-36 strain) infested with NFM. Hens were genotyped using a MHC microsatellite marker (LEI0258) and associations between MHC haplotype and NFM density were tested. The highest peak NFM populations occurred more often on hens with the B15 haplotype versus the B21 haplotype (P = 0.012), which supported the results of the congenic study. These data indicate the avian MHC influences ectoparasite resistance, which is relevant to disease ecology and avian-ectoparasite interaction. PMID:18626638

  4. References for Haplotype Imputation in the Big Data Era

    PubMed Central

    Li, Wenzhi; Xu, Wei; Li, Qiling; Ma, Li; Song, Qing

    2016-01-01

    Imputation is a powerful in silico approach to fill in those missing values in the big datasets. This process requires a reference panel, which is a collection of big data from which the missing information can be extracted and imputed. Haplotype imputation requires ethnicity-matched references; a mismatched reference panel will significantly reduce the quality of imputation. However, currently existing big datasets cover only a small number of ethnicities, there is a lack of ethnicity-matched references for many ethnic populations in the world, which has hampered the data imputation of haplotypes and its downstream applications. To solve this issue, several approaches have been proposed and explored, including the mixed reference panel, the internal reference panel and genotype-converted reference panel. This review article provides the information and comparison between these approaches. Increasing evidence showed that not just one or two genetic elements dictate the gene activity and functions; instead, cis-interactions of multiple elements dictate gene activity. Cis-interactions require the interacting elements to be on the same chromosome molecule, therefore, haplotype analysis is essential for the investigation of cis-interactions among multiple genetic variants at different loci, and appears to be especially important for studying the common diseases. It will be valuable in a wide spectrum of applications from academic research, to clinical diagnosis, prevention, treatment, and pharmaceutical industry. PMID:27274952

  5. Complete MHC haplotype sequencing for common disease gene mapping.

    PubMed

    Stewart, C Andrew; Horton, Roger; Allcock, Richard J N; Ashurst, Jennifer L; Atrazhev, Alexey M; Coggill, Penny; Dunham, Ian; Forbes, Simon; Halls, Karen; Howson, Joanna M M; Humphray, Sean J; Hunt, Sarah; Mungall, Andrew J; Osoegawa, Kazutoyo; Palmer, Sophie; Roberts, Anne N; Rogers, Jane; Sims, Sarah; Wang, Yu; Wilming, Laurens G; Elliott, John F; de Jong, Pieter J; Sawcer, Stephen; Todd, John A; Trowsdale, John; Beck, Stephan

    2004-06-01

    The future systematic mapping of variants that confer susceptibility to common diseases requires the construction of a fully informative polymorphism map. Ideally, every base pair of the genome would be sequenced in many individuals. Here, we report 4.75 Mb of contiguous sequence for each of two common haplotypes of the major histocompatibility complex (MHC), to which susceptibility to >100 diseases has been mapped. The autoimmune disease-associated-haplotypes HLA-A3-B7-Cw7-DR15 and HLA-A1-B8-Cw7-DR3 were sequenced in their entirety through a bacterial artificial chromosome (BAC) cloning strategy using the consanguineous cell lines PGF and COX, respectively. The two sequences were annotated to encompass all described splice variants of expressed genes. We defined the complete variation content of the two haplotypes, revealing >18,000 variations between them. Average SNP densities ranged from less than one SNP per kilobase to >60. Acquisition of complete and accurate sequence data over polymorphic regions such as the MHC from large-insert cloned DNA provides a definitive resource for the construction of informative genetic maps, and avoids the limitation of chromosome regions that are refractory to PCR amplification. PMID:15140828

  6. Reflections on ancestral haplotypes: medical genomics, evolution, and human individuality.

    PubMed

    Steele, Edward J

    2014-01-01

    The major histocompatibility complex (MHC), once labelled the "sphinx of immunology" by Jan Klein, provides powerful challenges to evolutionary thinking. This essay highlights the main discoveries that established the block ancestral haplotype structure of the MHC and the wider genome, focusing on the work by the Perth (Australia) group, led by Roger Dawkins, and the Boston group, led by Chester Alper and Edmond Yunis. Their achievements have been overlooked in the rush to sequence the first and subsequent drafts of the human genome. In Caucasoids, where most of the detailed work has been done, about 70% of all known allelic MHC diversity can be accounted for by 30 or so ancestral haplotypes (AHs), or conserved sequences of many mega-bases, and their recombinants. The block haplotype structure of the genome, as shown for the MHC (and other genetic regions), is a story that needs to be understood in its own right, particularly given the promotion of the "HapMap" project and single nucleotide polymorphism (SNP) linkage disequilibrium (LD) analysis, which has been wrongly touted as the only way to pinpoint those genes that are important in genetic disorders or other desired (qualitative) characteristics. PMID:25544323

  7. Mitochondrial Haplotypes Influence Metabolic Traits in Porcine Transmitochondrial Cybrids

    PubMed Central

    Yu, Guanghui; Xiang, Hai; Tian, Jianhui; Yin, Jingdong; Pinkert, Carl A.; Li, Qiuyan; Zhao, Xingbo

    2015-01-01

    In farm animals, mitochondrial DNA mutations exist widely across breeds and individuals. In order to identify differences among mtDNA haplotypes, two porcine transmitochondrial cybrids were generated by fusion of a Lantang pig cell line devoid of mitochondrial DNA with enucleated cytoplasm from either a Large White pig or a Xiang pig harboring potentially divergent mitochondrial haplotypes. These cybrid cells were subjected to mitochondrial genome sequencing, copy number detecting and analysis of biochemical traits including succinate dehydrogenase (SDH) activity, ATP content and susceptibility to reactive oxygen species (ROS). The Lantang and Xiang mitochondrial genomes were highly homologous with only 18 polymorphic sites, and differed radically from the Large White with 201 and 198 mutations respectively. The Large White and Xiang cybrids exhibited similar mtDNA copy numbers and different values among biochemical traits, generated greater ROS production (P < 0.05) and less SDH activity (P < 0.05) and a lesser ATP content (P < 0.05). The results show that functional differences exist between cybrid cells which differ in mitochondrial genomic background. In conclusion, transmitochondrial cybrids provide the first direct evidence on pig biochemical traits linking different mitochondrial genome haplotypes. PMID:26285652

  8. Intrahaplotypic Variants Differentiate Complex Linkage Disequilibrium within Human MHC Haplotypes

    PubMed Central

    Lam, Tze Hau; Tay, Matthew Zirui; Wang, Bei; Xiao, Ziwei; Ren, Ee Chee

    2015-01-01

    Distinct regions of long-range genetic fixation in the human MHC region, known as conserved extended haplotypes (CEHs), possess unique genomic characteristics and are strongly associated with numerous diseases. While CEHs appear to be homogeneous by SNP analysis, the nature of fine variations within their genomic structure is unknown. Using multiple, MHC-homozygous cell lines, we demonstrate extensive sequence conservation in two common Asian MHC haplotypes: A33-B58-DR3 and A2-B46-DR9. However, characterization of phase-resolved MHC haplotypes revealed unique intra-CEH patterns of variation and uncovered 127 single nucleotide variants (SNVs) which are missing from public databases. We further show that the strong linkage disequilibrium structure within the human MHC that typically confounds precise identification of genetic features can be resolved using intra-CEH variants, as evidenced by rs3129063 and rs448489, which affect expression of ZFP57, a gene important in methylation and epigenetic regulation. This study demonstrates an improved strategy that can be used towards genetic dissection of diseases. PMID:26593880

  9. Mapping MHC haplotype effects in unrelated donor hematopoietic cell transplantation

    PubMed Central

    Malkki, Mari; Horowitz, Mary M.; Spellman, Stephen R.; Haagenson, Michael D.; Wang, Tao

    2013-01-01

    Life-threatening risks associated with HLA-mismatched unrelated donor hematopoietic cell transplantation limit its general application for the treatment of blood diseases. The increased risks might be explained by undetected genetic variation within the highly polymorphic major histocompatibility complex (MHC) region. We retrospectively assessed each of 1108 MHC region single nucleotide polymorphisms (SNPs) in 2628 patients and their HLA-mismatched unrelated donors to determine whether SNPs are associated with the risk of mortality, disease-free survival, transplant-related mortality, relapse, and acute and chronic graft-versus-host disease (GVHD). Multivariate analysis adjusted for HLA mismatching and nongenetic variables associated with each clinical end point. Twelve SNPs were identified as transplantation determinants. SNP-associated risks were conferred by either patient or donor SNP genotype or by patient-donor SNP mismatching. Risks after transplantation increased with increasing numbers of unfavorable SNPs. SNPs that influenced acute GVHD were independent of those that affected risk of chronic GVHD and relapse. HLA haplotypes differed with respect to haplotype content of (un)favorable SNPs. Outcome after HLA-mismatched unrelated donor transplantation is influenced by MHC region variation that is undetected with conventional HLA typing. Knowledge of the SNP content of HLA haplotypes provides a means to estimate risks prior to transplantation and to lower complications through judicious selection of donors with favorable MHC genetics. PMID:23305741

  10. RAPID ASSIGNMENT OF SWINE LEUKOCYTE ANTIGEN (SLA) HAPLOTYPES IN PEDIGREED HERDS USING A POLYMERASE CHAIN REACTION BASED ASSAY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We present a simple assay to determine the SLA haplotypes of animals within two experimental herds of MHC defined miniature pigs. The Yucatan Miniature Pigs have four founder haplotypes (w, x, y, z) and one recombinant haplotype (q). The NIH Miniature Pigs have three founder haplotypes (a, c, d) an...

  11. The Children's War: Towards Peace in Sierra Leone. A Field Report Assessing the Protection and Assistance Needs of Sierra Leonean Children and Adolescents.

    ERIC Educational Resources Information Center

    Sommers, Marc

    Based on a 3-week field visit to Sierra Leone and Guinea, this report investigates why children (ages 0-17) have become key figures in Sierra Leone's civil war, and explores the problems that war has caused them. The report describes significant new effects of violence on three groups of Sierra Leonean children, very few of whom have received any…

  12. Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling

    PubMed Central

    Yang, Wei; Burkhardt, Britta; Fischer, Luise; Beirow, Maja; Bork, Nadja; Wönne, Eva C.; Wagner, Cornelia; Husen, Bettina; Zeilinger, Katrin; Liu, Liegang; Nussler, Andreas K.

    2015-01-01

    Aging is characterized by a progressive decrease of cellular functions, because cells gradually lose their capacity to respond to injury. Increased oxidative stress is considered to be one of the major contributors to age-related changes in all organs including the liver. Our study has focused on elucidating whether important antioxidative enzymes, the mTOR pathway, and MAPKs exhibit age-dependent changes in the liver of rats during aging. We found an age-dependent increase of GSH in the cytosol and mitochondria. The aged liver showed an increased SOD enzyme activity, while the CAT enzyme activity decreased. HO-1 and NOS-2 gene expression was lower in adult rats, but up-regulated in aged rats. Western blot analysis revealed that SOD1, SOD2, GPx, GR, γ-GCL, and GSS were age-dependent up-regulated, while CAT remained constant. We also demonstrated that the phosphorylation of Akt, JNK, p38, and TSC2Ser1254 decreased while ERK1/2 and TSC2Thr1462 increased age-dependently. Furthermore, our data show that the mTOR pathway seems to be activated in livers of aged rats, and hence stimulating cell proliferation/regeneration, as confirmed by an age-dependent increase of PCNA and p-eIF4ESer209 protein expression. Our data may help to explain the fact that liver cells only proliferate in cases of necessity, like injury and damage. In summary, we have demonstrated that, age-dependent changes of the antioxidant system and stress-related signaling pathways occur in the livers of rats, which may help to better understand organ aging. PMID:27004051

  13. Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis.

    PubMed

    Martí, Joaquín; Santa-Cruz, María C; Hervás, José P; Bayer, Shirley A; Villegas, Sandra

    2016-01-01

    Ataxias are neurological disorders associated with the degeneration of Purkinje cells (PCs). Homozygous weaver mice (wv/wv) have been proposed as a model for hereditary cerebellar ataxia because they present motor abnormalities and PC loss. To ascertain the physiopathology of the weaver condition, the development of the cerebellar cortex lobes was examined at postnatal day (P): P8, P20 and P90. Three approaches were used: 1) quantitative determination of several cerebellar features; 2) qualitative evaluation of the developmental changes occurring in the cortical lobes; and 3) autoradiographic analyses of PC generation and placement. Our results revealed a reduction in the size of the wv/wv cerebellum as a whole, confirming previous results. However, as distinguished from these reports, we observed that quantified parameters contribute differently to the abnormal growth of the wv/wv cerebellar lobes. Qualitative analysis showed anomalies in wv/wv cerebellar cytoarchitecture, depending on the age and lobe analyzed. Such abnormalities included the presence of the external granular layer after P20 and, at P90, ectopic cells located in the molecular layer following several placement patterns. Finally, we obtained autoradiographic evidence that wild-type and wv/wv PCs presented similar neurogenetic timetables, as reported. However, the innovative character of this current work lies in the fact that the neurogenetic gradients of wv/wv PCs were not modified from P8 to P90. A tendency for the accumulation of late-formed PCs in the anterior and posterior lobes was found, whereas early-generated PCs were concentrated in the central and inferior lobes. These data suggested that wv/wv PCs may migrate properly to their final destinations. The extrapolation of our results to patients affected with cerebellar ataxias suggests that all cerebellar cortex lobes are affected with several age-dependent alterations in cytoarchitectonics. We also propose that PC loss may be regionally

  14. Age-dependent biochemical dysfunction in skeletal muscle of triple-transgenic mouse model of Alzheimer`s disease.

    PubMed

    Monteiro-Cardoso, Vera F; Castro, Marisa; Oliveira, M M; Moreira, Paula I; Peixoto, Francisco; Videira, Romeu A

    2015-01-01

    The emergence of Alzheimer`s disease as a systemic pathology shifted the research paradigm toward a better understanding of the molecular basis of the disease considering the pathophysiological changes in both brain and peripheral tissues. In the present study, we evaluated the impact of disease progression on physiological relevant features of skeletal muscle obtained from 3, 6 and 12 month-old 3xTg-AD mice, a model of Alzheimer`s disease, and respective agematched nonTg mice. Our results showed that skeletal muscle functionality is already affected in 3-month-old 3xTg-AD mice as evidenced by deficient acetylcholinesterase and catalase activities as well as by alterations in fatty acid composition of mitochondrial membranes. Additionally, an age-dependent accumulation of amyloid-β1-40 peptide occurred in skeletal muscle of 3xTg-AD mice, an effect that preceded bioenergetics mitochondrial dysfunction, which was only detected at 12 months of age, characterized by decreased respiratory control ratio and ADP/O index and by an impairment of complex I activity. HPLC-MS/MS analyses revealed significant changes in phospholipid composition of skeletal muscle tissues from 3xTg-AD mice with 12 months of age when compared with age-matched nonTg mice. Increased levels of lyso-phosphatidylcholine associated with a decrease of phosphatidylcholine molecular species containing arachidonic acid were detected in 3xTg-AD mice, indicating an enhancement of phospholipase A2 activity and skeletal muscle inflammation. Additionally, a decrease of phosphatidylethanolamine plasmalogens content and an increase in phosphatidylinositol levels was observed in 3xTg-AD mice when compared with age-matched nonTg mice. Altogether, these observations suggest that the skeletal muscle of 3xTg-AD mice are more prone to oxidative and inflammatory events. PMID:25654504

  15. NbCSPR underlies age-dependent immune responses to bacterial cold shock protein in Nicotiana benthamiana.

    PubMed

    Saur, Isabel M L; Kadota, Yasuhiro; Sklenar, Jan; Holton, Nicholas J; Smakowska, Elwira; Belkhadir, Youssef; Zipfel, Cyril; Rathjen, John P

    2016-03-22

    Plants use receptor kinases (RKs) and receptor-like proteins (RLPs) as pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs) that are typical of whole classes of microbes. After ligand perception, many leucine-rich repeat (LRR)-containing PRRs interact with the LRR-RK BRI1-ASSOCIATED KINASE 1 (BAK1). BAK1 is thus expected to interact with unknown PRRs. Here, we used BAK1 as molecular bait to identify a previously unknown LRR-RLP required for the recognition of the csp22 peptide derived from bacterial cold shock protein. We established a method to identify proteins that interact with BAK1 only after csp22 treatment. BAK1 was expressed transiently in Nicotiana benthamiana and immunopurified after treatment with csp22. BAK1-associated proteins were identified by mass spectrometry. We identified several proteins including known BAK1 interactors and a previously uncharacterized LRR-RLP that we termed RECEPTOR-LIKE PROTEIN REQUIRED FOR CSP22 RESPONSIVENESS (NbCSPR). This RLP associates with BAK1 upon csp22 treatment, and NbCSPR-silenced plants are impaired in csp22-induced defense responses. NbCSPR confers resistance to bacteria in an age-dependent and flagellin-induced manner. As such, it limits bacterial growth and Agrobacterium-mediated transformation of flowering N. benthamiana plants. Transgenic expression of NbCSPR into Arabidopsis thaliana conferred responsiveness to csp22 and antibacterial resistance. Our method may be used to identify LRR-type RKs and RLPs required for PAMP perception/responsiveness, even when the active purified PAMP has not been defined. PMID:26944079

  16. Novel age-dependent learning deficits in a mouse model of Alzheimer’s disease: implications for translational research

    PubMed Central

    Montgomery, K. S.; Simmons, R. K.; Edwards, G.; Nicolle, M. M.; Gluck, M. A.; Myers, C. E.; Bizon, J. L.

    2015-01-01

    Computational modeling predicts that the hippocampus plays an important role in the ability to apply previously learned information to novel problems and situations (referred to as the ability to generalize information or simply as ‘transfer learning’). These predictions have been tested in humans using a computer-based task on which individuals with hippocampal damage are able to learn a series of complex discriminations with two stimulus features (shape and color), but are impaired in their ability to transfer this information to newly configured problems in which one of the features is altered. This deficit occurs despite the fact that the feature predictive of the reward (the relevant information) is not changed. The goal of the current study was to develop a mouse analog of transfer learning and to determine if this new task was sensitive to pathological changes in a mouse model of AD. We describe a task in which mice were able to learn a series of concurrent discriminations that contained two stimulus features (odor and digging media) and could transfer this learned information to new problems in which the irrelevant feature in each discrimination pair was altered. Moreover, we report age-dependent deficits specific to transfer learning in APP+PS1 mice relative to nontransgenic littermates. The robust impairment in transfer learning may be more sensitive to AD-like pathology than traditional cognitive assessments in that no deficits were observed in the APP+PS1 mice on the widely used Morris water maze task. These data describe a novel and sensitive paradigm to evaluate mnemonic decline in AD mouse models that has unique translational advantages over standard species-specific cognitive assessments (e.g. water maze for rodent and delayed paragraph recall for humans). PMID:19720431

  17. Age-Dependent Biochemical Dysfunction in Skeletal Muscle of Triple-Transgenic Mouse Model of Alzheimer`s Disease

    PubMed Central

    Monteiro-Cardoso, Vera F.; Castro, Marisa; Oliveira, M.M.; Moreira, Paula I.; Peixoto, Francisco; A.Videira, Romeu

    2015-01-01

    The emergence of Alzheimer`s disease as a systemic pathology shifted the research paradigm toward a better understanding of the molecular basis of the disease considering the pathophysiological changes in both brain and peripheral tissues. In the present study, we evaluated the impact of disease progression on physiological relevant features of skeletal muscle obtained from 3, 6 and 12 month-old 3xTg-AD mice, a model of Alzheimer`s disease, and respective agematched nonTg mice. Our results showed that skeletal muscle functionality is already affected in 3-month-old 3xTg-AD mice as evidenced by deficient acetylcholinesterase and catalase activities as well as by alterations in fatty acid composition of mitochondrial membranes. Additionally, an age-dependent accumulation of amyloid-β1-40 peptide occurred in skeletal muscle of 3xTg-AD mice, an effect that preceded bioenergetics mitochondrial dysfunction, which was only detected at 12 months of age, characterized by decreased respiratory control ratio and ADP/O index and by an impairment of complex I activity. HPLC-MS/MS analyses revealed significant changes in phospholipid composition of skeletal muscle tissues from 3xTg-AD mice with 12 months of age when compared with age-matched nonTg mice. Increased levels of lyso-phosphatidylcholine associated with a decrease of phosphatidylcholine molecular species containing arachidonic acid were detected in 3xTg-AD mice, indicating an enhancement of phospholipase A2 activity and skeletal muscle inflammation. Additionally, a decrease of phosphatidylethanolamine plasmalogens content and an increase in phosphatidylinositol levels was observed in 3xTg-AD mice when compared with age-matched nonTg mice. Altogether, these observations suggest that the skeletal muscle of 3xTg-AD mice are more prone to oxidative and inflammatory events. PMID:25654504

  18. Age-Dependent Resistance to Excitotoxicity in Htt CAG140 Mice and the Effect of Strain Background

    PubMed Central

    Strong, Melissa K.; Southwell, Amber L.; Yonan, Jennifer M.; Hayden, Michael R.; MacGregor, Grant R.; Thompson, Leslie M.; Steward, Oswald

    2013-01-01

    Mouse strain background can influence vulnerability to excitotoxic neuronal cell death and potentially modulate phenotypes in transgenic mouse models of human disease. Evidence supports a contribution of excitotoxicity to the selective death of medium spiny neurons in Huntington’s disease (HD). Here, we assess whether strain differences in excitotoxic vulnerability influence striatal cell death in a knock-in mouse model of HD. Previous studies that evaluated resistance to excitotoxic lesions in several mouse models of HD had variable outcomes. In the present study, we directly compare one model on two different background strains to test the contribution of strain to excitotoxicity-mediated neurodegeneration. Mice of the FVB/N strain, which are highly vulnerable to excitotoxicity, become extremely resistant to quinolinic acid-induced striatal neurodegeneration with age, when carrying a huntingtin (Htt) allele expressing a HD transgene (CAG140). The resistance is much greater than the age-dependent resistance that has been previously reported in YAC128 mice. By 12 months of age, both heterozygous and homozygous FVB.CAG140 mice displayed virtually complete resistance to quinolinic acid-induced striatal neurodegeneration. A similar resistance develops in CAG140 mice on a C57BL/6N background although the effect size is smaller because C57BL/6N mice are already resistant due to genetic background. In a direct comparison with the YAC128 mice, FVB.CAG140 mice have greater resistance. FVB.CAG140 mice are also resistant to neurodegeneration following kainic acid-induced status epilepticus suggesting the existence of a common cellular mechanism that provides protection against multiple types of excitotoxic insult. These findings establish FVB.CAG140 mice as a useful model to investigate the cellular and molecular mechanisms that confer neuroprotection against excitotoxicity. PMID:23833693

  19. Age-dependent survival of island vs. mainland populations of two avian scavengers: delving into migration costs.

    PubMed

    Sanz-Aguilar, Ana; De Pablo, Félix; Donázar, José Antonio

    2015-10-01

    Large terrestrial long-lived birds (including raptors) are typically sedentary on islands, even when they are migratory on the mainland. Density-dependent variation in the age at first breeding has been described as responsible for the long-term persistence of long-lived bird populations on islands. However, sedentary island populations may also benefit from higher survival rates derived from the absence of migration costs, especially for young individuals. Thus, sedentary island populations can mimic a natural experiment to study migration costs. We estimated the age-dependent survival of two sedentary raptors on the island of Menorca (Egyptian vultures Neophron percnopterus and red kites Milvus milvus) and compared these estimates with those reported for other migratory and sedentary populations. In Menorca, Egyptian vultures, but not red kites, showed low levels of human-related mortality resulting in extremely high survival probabilities, probably due to different diet choices and behavioral patterns. Juvenile Egyptian vultures and red kites in the studied population had lower survival probabilities than adults. This difference, however, was smaller than those reported for mainland migrant populations, which showed a lower juvenile survival rate. In fact, between-population comparisons suggested that survival of the young in migrant populations may be triggered by mortality factors in wintering areas. In contrast, adult survival may respond to mortality factors in breeding areas. Our results suggest that raptor species that become sedentary on islands may benefit from higher pre-breeder survival prospects in comparison with their mainland migrant counterparts. This fact, in combination with an earlier age at first reproduction, may facilitate their persistence. PMID:26013875

  20. Age-dependent uncoupling of mitochondria from Ca2⁺ release units in skeletal muscle.

    PubMed

    Pietrangelo, Laura; D'Incecco, Alessandra; Ainbinder, Alina; Michelucci, Antonio; Kern, Helmut; Dirksen, Robert T; Boncompagni, Simona; Protasi, Feliciano

    2015-11-01

    Calcium release units (CRUs) and mitochondria control myoplasmic [Ca2+] levels and ATP production in muscle, respectively. We recently reported that these two organelles are structurally connected by tethers, which promote proximity and proper Ca2+ signaling.Here we show that disposition, ultrastructure, and density of CRUs and mitochondria and their reciprocal association are compromised in muscle from aged mice. Specifically, the density of CRUs and mitochondria is decreased in muscle fibers from aged (>24 months) vs. adult (3-12 months), with an increased percentage of mitochondria being damaged and misplaced from their normal triadic position. A significant reduction in tether (13.8 ± 0.4 vs. 5.5 ± 0.3 tethers/100 µm2) and CRU-mitochondrial pair density (37.4 ± 0.8 vs. 27.0 ± 0.7 pairs/100 µm2) was also observed in aged mice. In addition, myoplasmic Ca2+ transient (1.68 ± 0.08 vs 1.37 ± 0.03) and mitochondrial Ca2+ uptake (9.6 ± 0.050 vs 6.58 ± 0.54) during repetitive high frequency tetanic stimulation were significantly decreased. Finally oxidative stress, assessed from levels of 3-nitrotyrosine (3-NT), Cu/Zn superoxide-dismutase (SOD1) and Mn superoxide dismutase (SOD2) expression, were significantly increased in aged mice. The reduced association between CRUs and mitochondria with aging may contribute to impaired cross-talk between the two organelles, possibly resulting in reduced efficiency in activity-dependent ATP production and, thus, to age-dependent decline of skeletal muscle performance. PMID:26485763

  1. Age Dependency of GLI Reference Values Compared with Paediatric Lung Function Data in Two German Studies (GINIplus and LUNOKID)

    PubMed Central

    Hüls, Anke; Krämer, Ursula; Gappa, Monika; Müller-Brandes, Christine; Schikowski, Tamara; von Berg, Andrea; Hoffmann, Barbara; Schuster, Antje; Wisbauer, Matthias; Flexeder, Claudia; Heinrich, Joachim; Schulz, Holger; Berdel, Dietrich

    2016-01-01

    A hallmark of the newly published GLI (Global Lungs Initiative) spirometric reference values is their "all-age" (3-95yr) predictive power, accomplished by incorporating non-linear age dependencies into modelling parameters. This modelling strategy is especially promising for the age range of puberty; however, the performance of GLI-values for adolescents is currently unknown. We calculated GLI-based z-scores for children/adolescents without apparent respiratory diseases from two different German studies, LUNOKID (N = 1943, 4–19 years) and GINIplus (N = 1042, 15 years) and determined the goodness of fit for specific age groups. We defined fit sufficient if the absolute mean of z-scores was <0.5. For children (<10yr) the mean GLI-based z-scores for FEV1 and FVC reached a good fit with mean z-scores for FEV1 between -0.11 and 0.01 and mean z-scores for FVC between 0.01 and 0.16, but larger deviations were observed in adolescents, especially boys (mean z-score -0.58 for FEV1 and -0.57 for FVC in GINIplus). The fit for FEV1/FVC was sufficient. GLI reference values provided reasonable estimates for the individuals enrolled in our studies, which span the age range of lung growth and development. However, we found that GLI-predictions overestimated lung volumes, especially those for German adolescent boys, which may, left unrecognised, lead to erroneous diagnosis of lung disease. Caution should be taken when applying these reference values to epidemiologic studies. PMID:27438002

  2. Haplotypes of the steroid 21-hydroxylase gene region encoding mild steroid 21-hydroxylase deficiency.

    PubMed Central

    Haglund-Stengler, B; Martin Ritzén, E; Gustafsson, J; Luthman, H

    1991-01-01

    Haplotypes of the complement 4 (C4) and steroid 21-hydroxylase [21-OHase; steroid hydrogen-donor: oxygen oxidoreductase (21-hydroxylating), EC 1.14.99.10] repeated gene complex were studied in nine families with at least one member affected with a mild form of 21-OHase deficiency. DNA probes from different parts of the repeated C4/21-OHase unit were used to follow the segregation of hybridization patterns in the families. Ten structurally distinct haplotypes of the C4/21-OHase gene region were identified, and the encoded phenotype was assigned to 34 of the 36 C4/21-OHase haplotypes. Four structurally different haplotypes with three C4/21-OHase repeat units were found. Eight of the nine haplotypes found with triplications of the C4/21-OHase repeat unit encoded the mild form of 21-OHase deficiency, whereas one particular triplicated haplotype encoded a severe form of the disease. In one case the mild form of 21-OHase deficiency was encoded by a haplotype with a single C4/21-OHase repeat unit. Mild 21-OHase deficiency was predicted in a patient by the presence of a triplicated haplotype. The finding of deranged 21-OHase genes on all triplicated C4/21-OHase haplotypes indicate that most of these common haplotypes carry mutated 21-OHase genes, and thus may cause functional polymorphism of general importance in the population. PMID:1924294

  3. Genomic evaluation of HLA-DR3+ haplotypes associated with type 1 diabetes.

    PubMed

    Kumar, Neeraj; Kaur, Gurvinder; Tandon, Nikhil; Kanga, Uma; Mehra, Narinder K

    2013-04-01

    We have defined three sets of HLA-DR3(+) haplotypes that provide maximum risk of type 1 disease development in Indians: (1) a diverse array of B8-DR3 haplotypes, (2) A33-B58-DR3 haplotype, and (3) A2-B50-DR3 occurring most predominantly in this population. Further analysis has revealed extensive diversity in B8-DR3 haplotypes, particularly at the HLA-A locus, in contrast to the single fixed HLA-A1-B8-DR3 haplotype (generally referred to as AH8.1) reported in Caucasians. However, the classical AH8.1 haplotype was rare and differed from the Caucasian counterpart at multiple loci. In our study, HLA-A26-B8-DR3 (AH8.2) was the most common B8-DR3 haplotype constituting >50% of the total B8-DR3 haplotypes. Further, A2-B8-DR3 contributed the maximum risk (RR = 48.7) of type 1 diabetes, followed by A2-B50-DR3 (RR = 9.4), A33-B58-DR3 (RR = 6.6), A24-B8-DR3 (RR = 4.5), and A26-B8-DR3 (RR = 4.2). Despite several differences, the disease-associated haplotypes in Indian and Caucasian populations share a frozen DR3-DQ2 block, suggesting a common ancestor from which multiple haplotypes evolved independently. PMID:23387390

  4. Genealogical analysis of cystic fibrosis families and chromosome 7q RFLP haplotypes in the Hutterite Brethren.

    PubMed Central

    Fujiwara, T M; Morgan, K; Schwartz, R H; Doherty, R A; Miller, S R; Klinger, K; Stanislovitis, P; Stuart, N; Watkins, P C

    1989-01-01

    In the 100-year period 1880-1980 the Hutterite population increased from about 442 to 23,000 individuals in North America. There are three endogamous subdivisions in this Caucasian genetic isolate. A total of 11 cystic fibrosis (CF) families from Canada and the United States were investigated, including at least two families from each of the three subdivisions, the Dariusleut, Lehrerleut, and Schmiedeleut. A study of RFLPs for the loci D7S8, D7S23, MET, and D7S18 (also called D7S16) in the region of the CF gene in 10 families shows considerable genetic variability. There were three different extended CF gene-region haplotypes on CF chromosomes (CF haplotypes), and there were 13 different extended CF gene-region haplotypes on normal chromosomes (normal haplotypes). The three CF haplotypes have different D7S23 and MET haplotypes. Parents who have the same CF haplotype are, on the average, more closely related than parents who have different haplotypes, but only within the same subdivision. A marriage node graph of 11 families illustrates the complexity of Hutterite genealogies. The frequency distribution of CF haplotypes in the Hutterite sample differs notably from those of larger agglomerates of family data from collaborative studies, with respect to D7S8, MET haplotypes, and D7S23 haplotypes. We propose that there were at least three CF carriers among the founders of the Hutterite population and that copies of a particular CF haplotype in current individuals are identical by descent. The alternative that one or more genetically distinguishable CF haplotypes resulted from recombination since the founding of the population is considered to be less likely. PMID:2563632

  5. The Impact of the West Africa Ebola Outbreak on Obstetric Health Care in Sierra Leone

    PubMed Central

    Brolin Ribacke, Kim J.; van Duinen, Alex J.; Nordenstedt, Helena; Höijer, Jonas; Molnes, Ragnhild; Froseth, Torunn Wigum; Koroma, AP; Darj, Elisabeth; Bolkan, Håkon Angel; Ekström, AnnaMia

    2016-01-01

    Background As Sierra Leone celebrates the end of the Ebola Virus Disease (EVD) outbreak, we can begin to fully grasp its impact on already weak health systems. The EVD outbreak in West Africa forced many hospitals to close down or reduce their activity, either to prevent nosocomial transmission or because of staff shortages. The aim of this study is to assess the potential impact of EVD on nationwide access to obstetric care in Sierra Leone. Methods and Findings Community health officers collected weekly data between January 2014—May 2015 on in-hospital deliveries and caesarean sections (C-sections) from all open facilities (public, private for-profit and private non-profit sectors) offering emergency obstetrics in Sierra Leone. This was compared to official data of EVD cases per district. Logistic and Poisson regression analyses were used to compute risk and rate estimates. Nationwide, the number of in-hospital deliveries and C-sections decreased by over 20% during the EVD outbreak. The decline occurred early on in the EVD outbreak and was mainly attributable to the closing of private not-for-profit hospitals rather than government facilities. Due to difficulties in collecting data in the midst of an epidemic, limitations of this study include some missing data points. Conclusions Both the number of in-hospital deliveries and C-sections substantially declined shortly after the onset of the EVD outbreak. Since access to emergency obstetric care, like C-sections, is associated with decreased maternal mortality, many women are likely to have died due to the reduced access to appropriate care during childbirth. Future research on indirect health effects of health system breakdown should ideally be nationwide and continue also into the recovery phase. It is also important to understand the mechanisms behind the deterioration so that important health services can be reestablished. PMID:26910462

  6. The free health care initiative: how has it affected health workers in Sierra Leone?

    PubMed Central

    Witter, Sophie; Wurie, Haja; Bertone, Maria Paola

    2016-01-01

    There is an acknowledged gap in the literature on the impact of fee exemption policies on health staff, and, conversely, the implications of staffing for fee exemption. This article draws from five research tools used to analyse changing health worker policies and incentives in post-war Sierra Leone to document the effects of the Free Health Care Initiative (FHCI) of 2010 on health workers. Data were collected through document review (57 documents fully reviewed, published and grey); key informant interviews (23 with government, donors, NGO staff and consultants); analysis of human resource data held by the MoHS; in-depth interviews with health workers (23 doctors, nurses, mid-wives and community health officers); and a health worker survey (312 participants, including all main cadres). The article traces the HR reforms which were triggered by the FHCI and evidence of their effects, which include substantial increases in number and pay (particularly for higher cadres), as well as a reported reduction in absenteeism and attrition, and an increase (at least for some areas, where data is available) in outputs per health worker. The findings highlight how a flagship policy, combined with high profile support and financial and technical resources, can galvanize systemic changes. In this regard, the story of Sierra Leone differs from many countries introducing fee exemptions, where fee exemption has been a stand-alone programme, unconnected to wider health system reforms. The challenge will be sustaining the momentum and the attention to delivering results as the FHCI ceases to be an initiative and becomes just ‘business as normal’. The health system in Sierra Leone was fragile and conflict-affected prior to the FHCI and still faces significant challenges, both in human resources for health and more widely, as vividly evidenced by the current Ebola crisis. PMID:25797469

  7. The free health care initiative: how has it affected health workers in Sierra Leone?

    PubMed

    Witter, Sophie; Wurie, Haja; Bertone, Maria Paola

    2016-02-01

    There is an acknowledged gap in the literature on the impact of fee exemption policies on health staff, and, conversely, the implications of staffing for fee exemption. This article draws from five research tools used to analyse changing health worker policies and incentives in post-war Sierra Leone to document the effects of the Free Health Care Initiative (FHCI) of 2010 on health workers.Data were collected through document review (57 documents fully reviewed, published and grey); key informant interviews (23 with government, donors, NGO staff and consultants); analysis of human resource data held by the MoHS; in-depth interviews with health workers (23 doctors, nurses, mid-wives and community health officers); and a health worker survey (312 participants, including all main cadres). The article traces the HR reforms which were triggered by the FHCI and evidence of their effects, which include substantial increases in number and pay (particularly for higher cadres), as well as a reported reduction in absenteeism and attrition, and an increase (at least for some areas, where data is available) in outputs per health worker. The findings highlight how a flagship policy, combined with high profile support and financial and technical resources, can galvanize systemic changes. In this regard, the story of Sierra Leone differs from many countries introducing fee exemptions, where fee exemption has been a stand-alone programme, unconnected to wider health system reforms. The challenge will be sustaining the momentum and the attention to delivering results as the FHCI ceases to be an initiative and becomes just 'business as normal'. The health system in Sierra Leone was fragile and conflict-affected prior to the FHCI and still faces significant challenges, both in human resources for health and more widely, as vividly evidenced by the current Ebola crisis. PMID:25797469

  8. Tertiary carbonate-dissolution cycles on the Sierra Leone Rise, eastern equatorial Atlantic Ocean

    USGS Publications Warehouse

    Dean, W.E.; Gardner, J.V.; Cepek, P.

    1981-01-01

    Most of the Tertiary section on Sierra Leone Rise off northwest Africa consists of chalk, marl, and limestone that show cyclic alterations of clay-rich and clay-poor beds about 20-60 cm thick. On the basis of biostratigraphic accumulation rates, the cycles in Oligocene and Miocene chalk have periods which average about 44,000 years, and those in Eocene siliceous limestone have periods of 4000-27,000 years. Several sections were sampled in detail to further define the cycles in terms of content of CaCO3, clay minerals, and relative abundances of calcareous nannofossils. Extending information gained by analyses of Pleistocene cores from the continental margin of northwest Africa to the Tertiary cycles on Sierra Leone Rise, both dilution by noncarbonate material and dissolution of CaCO3 could have contributed to the observed relative variations in clay and CaCO3. However, dissolution of CaCO3 as the main cause of the carbonate-clay cycles on the Sierra Leone Rise, rather than dilution by clay, is suggested by the large amount of change (several thousand percent) in terrigenous influx required to produce the observed variations in amount of clay and by the marked increase in abundance of dissolution-resistant discoasters relative to more easily dissolved coccoliths in low-carbonate parts of cycles. The main cause of dissolution of CaCO3 was shoaling of the carbonate compensation depth (CCD) during the early Neogene and climatically induced fluctuations in the thickness of Antarctic Bottom Water. ?? 1981.

  9. An estimate of hernia prevalence in Sierra Leone from a nationwide community survey

    PubMed Central

    Patel, Hiten D; Groen, Reinou S; Kamara, Thaim B; Samai, Mohamed; Farahzad, Mina M; Cassidy, Laura D; Kushner, Adam L; Wren, Sherry M

    2016-01-01

    Purpose A large number of unrepaired inguinal hernias is expected in sub-Saharan Africa where late presentation often results in incarceration, strangulation, or giant scrotal hernias. However, no representative population-based data is available to quantify the prevalence of hernias. We present data on groin masses in Sierra Leone to estimate prevalence, barriers to care, and associated disability. Methods A cluster randomized, cross-sectional household survey of 75 clusters of 25 households with 2 respondents each was designed to calculate the prevalence of and disability caused by groin hernias in Sierra Leone using a verbal head-to-toe examination. Barriers to hernia repairs were assessed by asking participants the main reason for delay in surgical care. Results Information was obtained from 3645 respondents in 1843 households, of which 1669 (46%) were male and included in the study. In total, 117 males or 7.01% (95% CI 5.64-8.38) reported a soft or reducible swelling likely representing a hernia with four men having two masses. Of the 93.2% who indicated the need for health care, only 22.2% underwent a procedure, citing limited funds (59.0%) as the major barrier to care. On disability assessment, 20.2% were not able to work secondary to the groin swelling. Conclusions The results indicate groin masses represent a major burden for the male population in Sierra Leone. Improving access to surgical care for adult patients with hernias and early intervention for children will be vital to address the burden of disease and prevent complications or limitations of daily activity. PMID:24241327

  10. Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone.

    PubMed

    Tong, Yi-Gang; Shi, Wei-Feng; Liu, Di; Qian, Jun; Liang, Long; Bo, Xiao-Chen; Liu, Jun; Ren, Hong-Guang; Fan, Hang; Ni, Ming; Sun, Yang; Jin, Yuan; Teng, Yue; Li, Zhen; Kargbo, David; Dafae, Foday; Kanu, Alex; Chen, Cheng-Chao; Lan, Zhi-Heng; Jiang, Hui; Luo, Yang; Lu, Hui-Jun; Zhang, Xiao-Guang; Yang, Fan; Hu, Yi; Cao, Yu-Xi; Deng, Yong-Qiang; Su, Hao-Xiang; Sun, Yu; Liu, Wen-Sen; Wang, Zhuang; Wang, Cheng-Yu; Bu, Zhao-Yang; Guo, Zhen-Dong; Zhang, Liu-Bo; Nie, Wei-Min; Bai, Chang-Qing; Sun, Chun-Hua; An, Xiao-Ping; Xu, Pei-Song; Zhang, Xiang-Li-Lan; Huang, Yong; Mi, Zhi-Qiang; Yu, Dong; Yao, Hong-Wu; Feng, Yong; Xia, Zhi-Ping; Zheng, Xue-Xing; Yang, Song-Tao; Lu, Bing; Jiang, Jia-Fu; Kargbo, Brima; He, Fu-Chu; Gao, George F; Cao, Wu-Chun

    2015-08-01

    A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 × 10(-3) substitutions per site per year (95% highest posterior density interval, 1.04 × 10(-3) to 1.41 × 10(-3) substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics. PMID:25970247

  11. Rapid assessment of Ebola infection prevention and control needs--six districts, Sierra Leone, October 2014.

    PubMed

    Pathmanathan, Ishani; O'Connor, Katherine A; Adams, Monica L; Rao, Carol Y; Kilmarx, Peter H; Park, Benjamin J; Mermin, Jonathan; Kargbo, Brima; Wurie, Alie H; Clarke, Kevin R

    2014-12-12

    As of October 31, 2014, the Sierra Leone Ministry of Health and Sanitation had reported 3,854 laboratory-confirmed cases of Ebola virus disease (Ebola) since the outbreak began in May 2014; 199 (5.2%) of these cases were among health care workers. Ebola infection prevention and control (IPC) measures are essential to interrupt Ebola virus transmission and protect the health workforce, a population that is disproportionately affected by Ebola because of its increased risk of exposure yet is essential to patient care required for outbreak control and maintenance of the country's health system at large. To rapidly identify existing IPC resources and high priority outbreak response needs, an assessment by CDC Ebola Response Team members was conducted in six of the 14 districts in Sierra Leone, consisting of health facility observations and structured interviews with key informants in facilities and government district health management offices. Health system gaps were identified in all six districts, including shortages or absence of trained health care staff, personal protective equipment (PPE), safe patient transport, and standardized IPC protocols. Based on rapid assessment findings and key stakeholder input, priority IPC actions were recommended. Progress has since been made in developing standard operating procedures, increasing laboratory and Ebola treatment capacity and training the health workforce. However, further system strengthening is needed. In particular, a successful Ebola outbreak response in Sierra Leone will require an increase in coordinated and comprehensive district-level IPC support to prevent ongoing Ebola virus transmission in household, patient transport, and health facility settings. PMID:25503922

  12. Technical efficiency of peripheral health units in Pujehun district of Sierra Leone: a DEA application

    PubMed Central

    Renner, Ade; Kirigia, Joses M; Zere, Eyob A; Barry, Saidou P; Kirigia, Doris G; Kamara, Clifford; Muthuri, Lenity HK

    2005-01-01

    Background The Data Envelopment Analysis (DEA) method has been fruitfully used in many countries in Asia, Europe and North America to shed light on the efficiency of health facilities and programmes. There is, however, a dearth of such studies in countries in sub-Saharan Africa. Since hospitals and health centres are important instruments in the efforts to scale up pro-poor cost-effective interventions aimed at achieving the United Nations Millennium Development Goals, decision-makers need to ensure that these health facilities provide efficient services. The objective of this study was to measure the technical efficiency (TE) and scale efficiency (SE) of a sample of public peripheral health units (PHUs) in Sierra Leone. Methods This study applied the Data Envelopment Analysis approach to investigate the TE and SE among a sample of 37 PHUs in Sierra Leone. Results Twenty-two (59%) of the 37 health units analysed were found to be technically inefficient, with an average score of 63% (standard deviation = 18%). On the other hand, 24 (65%) health units were found to be scale inefficient, with an average scale efficiency score of 72% (standard deviation = 17%). Conclusion It is concluded that with the existing high levels of pure technical and scale inefficiency, scaling up of interventions to achieve both global and regional targets such as the MDG and Abuja health targets becomes far-fetched. In a country with per capita expenditure on health of about US$7, and with only 30% of its population having access to health services, it is demonstrated that efficiency savings can significantly augment the government's initiatives to cater for the unmet health care needs of the population. Therefore, we strongly recommend that Sierra Leone and all other countries in the Region should institutionalise health facility efficiency monitoring at the Ministry of Health headquarter (MoH/HQ) and at each health district headquarter. PMID:16354299

  13. Clinical Illness and Outcomes in Patients with Ebola in Sierra Leone

    PubMed Central

    Schieffelin, J.S.; Shaffer, J.G.; Goba, A.; Gbakie, M.; Gire, S.K.; Colubri, A.; Sealfon, R.S.G.; Kanneh, L.; Moigboi, A.; Momoh, M.; Fullah, M.; Moses, L.M.; Brown, B.L.; Andersen, K.G.; Winnicki, S.; Schaffner, S.F.; Park, D.J.; Yozwiak, N.L.; Jiang, P.-P.; Kargbo, D.; Jalloh, S.; Fonnie, M.; Sinnah, V.; French, I.; Kovoma, A.; Kamara, F.K.; Tucker, V.; Konuwa, E.; Sellu, J.; Mustapha, I.; Foday, M.; Yillah, M.; Kanneh, F.; Saffa, S.; Massally, J.L.B.; Boisen, M.L.; Branco, L.M.; Vandi, M.A.; Grant, D.S.; Happi, C.; Gevao, S.M.; Fletcher, T.E.; Fowler, R.A.; Bausch, D.G.; Sabeti, P.C.; Khan, S.H.; Garry, R.F.

    2014-01-01

    BACKGROUND Limited clinical and laboratory data are available on patients with Ebola virus disease (EVD). The Kenema Government Hospital in Sierra Leone, which had an existing infrastructure for research regarding viral hemorrhagic fever, has received and cared for patients with EVD since the beginning of the outbreak in Sierra Leone in May 2014. METHODS We reviewed available epidemiologic, clinical, and laboratory records of patients in whom EVD was diagnosed between May 25 and June 18, 2014. We used quantitative reverse-transcriptase–polymerase-chain-reaction assays to assess the load of Ebola virus (EBOV, Zaire species) in a subgroup of patients. RESULTS Of 106 patients in whom EVD was diagnosed, 87 had a known outcome, and 44 had detailed clinical information available. The incubation period was estimated to be 6 to 12 days, and the case fatality rate was 74%. Common findings at presentation included fever (in 89% of the patients), headache (in 80%), weakness (in 66%), dizziness (in 60%), diarrhea (in 51%), abdominal pain (in 40%), and vomiting (in 34%). Clinical and laboratory factors at presentation that were associated with a fatal outcome included fever, weakness, dizziness, diarrhea, and elevated levels of blood urea nitrogen, aspartate aminotransferase, and creatinine. Exploratory analyses indicated that patients under the age of 21 years had a lower case fatality rate than those over the age of 45 years (57% vs. 94%, P = 0.03), and patients presenting with fewer than 100,000 EBOV copies per milliliter had a lower case fatality rate than those with 10 million EBOV copies per milliliter or more (33% vs. 94%, P = 0.003). Bleeding occurred in only 1 patient. CONCLUSIONS The incubation period and case fatality rate among patients with EVD in Sierra Leone are similar to those observed elsewhere in the 2014 outbreak and in previous outbreaks. Although bleeding was an infrequent finding, diarrhea and other gastrointestinal manifestations were common. (Funded

  14. Uranium series isotopes concentration in sediments at San Marcos and Luis L. Leon reservoirs, Chihuahua, Mexico

    SciTech Connect

    Méndez-García, C.; Montero-Cabrera, M. E.; Renteria-Villalobos, M.; García-Tenorio, R.

    2008-01-01

    Spatial and temporal distribution of the radioisotopes concentrations were determined in sediments near the surface and core samples extracted from two reservoirs located in an arid region close to Chihuahua City, Mexico. At San Marcos reservoir one core was studied, while from Luis L. Leon reservoir one core from the entrance and another one close to the wall were investigated. ²³²Th-series, ²³⁸U-series, ⁴⁰K and ¹³⁷Cs activity concentrations (AC, Bq kg⁻¹) were determined by gamma spectrometry with a high purity Ge detector. ²³⁸U and ²³⁴U ACs were obtained by liquid scintillation and alpha spectrometry with a surface barrier detector. Dating of core sediments was performed applying CRS method to ²¹⁰Pb activities. Results were verified by ¹³⁷Cs AC. Resulting activity concentrations were compared among corresponding surface and core sediments. High ²³⁸U-series AC values were found in sediments from San Marcos reservoir, because this site is located close to the Victorino uranium deposit. Low AC values found in Luis L. Leon reservoir suggest that the uranium present in the source of the Sacramento – Chuviscar Rivers is not transported up to the Conchos River. Activity ratios (AR) ²³⁴U/²³⁸U and ²³⁸U/²²⁶Ra in sediments have values between 0.9–1.2, showing a behavior close to radioactive equilibrium in the entire basin. ²³²Th/²³⁸U, ²²⁸Ra/²²⁶Ra ARs are witnesses of the different geological origin of sediments from San Marcos and Luis L. Leon reservoirs.

  15. Uranium series isotopes concentration in sediments at San Marcos and Luis L. Leon reservoirs, Chihuahua, Mexico

    NASA Astrophysics Data System (ADS)

    Méndez-García, C.; Renteria-Villalobos, M.; García-Tenorio, R.; Montero-Cabrera, M. E.

    2014-07-01

    Spatial and temporal distribution of the radioisotopes concentrations were determined in sediments near the surface and core samples extracted from two reservoirs located in an arid region close to Chihuahua City, Mexico. At San Marcos reservoir one core was studied, while from Luis L. Leon reservoir one core from the entrance and another one close to the wall were investigated. 232Th-series, 238U-series, 40K and 137Cs activity concentrations (AC, Bq kg-1) were determined by gamma spectrometry with a high purity Ge detector. 238U and 234U ACs were obtained by liquid scintillation and alpha spectrometry with a surface barrier detector. Dating of core sediments was performed applying CRS method to 210Pb activities. Results were verified by 137Cs AC. Resulting activity concentrations were compared among corresponding surface and core sediments. High 238U-series AC values were found in sediments from San Marcos reservoir, because this site is located close to the Victorino uranium deposit. Low AC values found in Luis L. Leon reservoir suggest that the uranium present in the source of the Sacramento - Chuviscar Rivers is not transported up to the Conchos River. Activity ratios (AR) 234U/overflow="scroll">238U and 238U/overflow="scroll">226Ra in sediments have values between 0.9-1.2, showing a behavior close to radioactive equilibrium in the entire basin. 232Th/overflow="scroll">238U, 228Ra/overflow="scroll">226Ra ARs are witnesses of the different geological origin of sediments from San Marcos and Luis L. Leon reservoirs.

  16. Characterization of the dengue outbreak in Nuevo Leon state, Mexico, 2010.

    PubMed

    Leduc-Galindo, D; Gloria-Herrera, U; Rincón-Herrera, U; Ramos-Jiménez, J; Garcia-Luna, S; Arellanos-Soto, D; Mendoza-Tavera, N; Tavitas-Aguilar, I; Garcia-Garcia, E; Galindo-Galindo, E; Villarreal-Perez, J; Fernandez-Salas, I; Santiago, G A; Muñoz-Jordan, J; Rivas-Estilla, A M

    2015-04-01

    We studied serotypes circulating dengue virus (DENV) cases, entomological Breteau index, rain-fall index and epidemiology of groups affected during the 2010 outbreak in Nuevo Leon, Mexico. From 2,271 positive cases, 94% were dengue classic and 6% dengue hemorrhagic fever; DENV1 was mainly isolated (99%) (Central-American lineage of American-African-genotype). We found correlation between two environmental phenomena (Increment of rainfall and vector-indexes) (p ≤ 0.05) with epidemiological, clinical and risk of DENV-1 ongoing transmission. PMID:25573274

  17. Exponential prototype structures for (2+1)-dimensional Boiti-Leon-Pempinelli systems in mathematical physics

    NASA Astrophysics Data System (ADS)

    Baskonus, Haci Mehmet; Bulut, Hasan

    2016-04-01

    In this study, a new method called improved Bernoulli sub-equation function method has been proposed. This method is based on the Bernoulli sub-ODE method. After we mention the general properties of proposed method, we apply this algorithm to the (2 + 1)-dimensional Boiti-Leon-Pempinelli equation system. This gives us some new prototype solutions such as exponential and rational function solutions. Then, we have plotted two- and three-dimensional surfaces of analytical solutions. Finally, we have submitted a comprehensive conclusion.

  18. Review: Leon N. Cooper’s Science and Human Experience: Values, Culture, and the Mind

    PubMed Central

    Lynch, Gary S.

    2015-01-01

    Why are we reviewing a book written by someone who shared in the 1972 Nobel Prize in Physics for work on superconductivity? Because shortly after winning the prize, Leon N. Cooper transitioned into brain research—specifically, the biological basis of memory. He became director of the Brown University Institute for Brain and Neural Systems, whose interdisciplinary program allowed him to integrate research on the brain, physics, and even philosophy. His new book tackles a diverse spectrum of topics and questions, including these: Does science have limits? Where does order come from? Can we understand consciousness? PMID:27358665

  19. The Ebola virus disease outbreak and the mineral sectors of Guinea, Liberia, and Sierra Leone

    USGS Publications Warehouse

    Bermúdez-Lugo, Omayra; Menzie, William D.

    2015-01-01

    In response to the uncertainty surrounding the status of mineral projects in Guinea, Liberia, and Sierra Leone, the National Minerals Information Center compiled information on the distribution of mines, mineral facilities, and mineral projects under development in the three countries. This fact sheet provides information on the role that the mineral sector plays in their respective economies, on the operating status of mining projects through yearend 2014, and on the coordinated actions by mining companies to support governments and international relief organizations in their efforts to contain the EVD outbreak.

  20. Review: Leon N. Cooper's Science and Human Experience: Values, Culture, and the Mind.

    PubMed

    Lynch, Gary S

    2015-01-01

    Why are we reviewing a book written by someone who shared in the 1972 Nobel Prize in Physics for work on superconductivity? Because shortly after winning the prize, Leon N. Cooper transitioned into brain research-specifically, the biological basis of memory. He became director of the Brown University Institute for Brain and Neural Systems, whose interdisciplinary program allowed him to integrate research on the brain, physics, and even philosophy. His new book tackles a diverse spectrum of topics and questions, including these: Does science have limits? Where does order come from? Can we understand consciousness? PMID:27358665

  1. Parameters of deep melts in the Sierra-Leone region, Central Atlantic (data on melt inclusions)

    NASA Astrophysics Data System (ADS)

    Simonov, V. A.; Glazyrin, Yu. E.; Kovyazin, S. V.

    2003-04-01

    Samples, collected during 22 cruise of R/V "Academician Nikolaj Strakhov" in the Sierra Leone F.Z. Region, Central Atlantic (Peyve et al., 2000) were investigated. The features of geology and volcanism of this region were reviewed in the last publications (Peyve et al., 2003; Skolotnev et al., 2003). In the present report the results of melt inclusions study in olivines and in plagioclases from basalts are given. The experiments with inclusions were carried out according published procedure (Simonov, 1993; Sobolev, Danyushevsky, 1994). The compositions of inclusions were established using a "Camebax-micro" electron microprobe. Contents of trace, rare earth elements and water in inclusions were determined on ionic microprobe IMS-4f on procedure published in the work (Sobolev, 1996). The analysis of melt inclusions in olivines from basalts has shown, that the magmas of the Mid-Atlantic Ridge (MAR) Rift Zone in the Sierra-Leone Region have sufficiently high temperatures of crystallization -- 1275--1340^oC. Comparison of homogenization temperatures with liquidus temperatures calculated according PETROLOG (Danyushevsky, 2001) show, that the most of data agree with limits of used thermometers. The presence of such temperature characteristics testifies that the inclusions characterize parameters of deep melts. Primary magmas in this region, according estimation on procedure (Schilling et al., 1995), were formed at parameters of mantle melting near 1340--1370^oC and 50--60 km (Simonov et al., 2001). Comparison with data on trace and rare earth elements in melt inclusions in olivines from rocks 9^o N MAR (Sobolev, 1997) demonstrates, that on an interrelation La/Sm--Zr/Y inclusions in olivines from Sierra-Leone Region are close to data on normal melts formed during melting of mantle with formation about 5% of melt. On a character of distribution of trace and rare earth elements melts in the Sierra-Leone Region are closer to magmas from north segments of MAR (8^o N), than

  2. SELENIUM and arsenic concentrations in platinum group minerals of placer origin from Borneo and Sierra Leone

    NASA Astrophysics Data System (ADS)

    Hattori, K. H.; Johanson, B.; Cabri, L. J.

    2003-04-01

    Laurite grains were examined from the type locality, Pontijn River, Tanah Laur, Borneo and from South Tambanio River, S.E. Borneo, and erlichmanite grains from Sierra Leone. The Borneo samples are associated with ophiolite (Alpine-type) ultramafic rocks and the Sierra Leone samples with the layered Freetown Igneous Complex. Laurite grains from Borneo are sub-rounded to spherical with pits and show conchoidal fractures. They contain rare inclusions of an exsolved chalcopyrite+ bornite+ pentlandite mixture. On the other hand, the erlichmanite grains from Sierra Leone are euhedral with minor smooth edges and contain abundant rounded inclusions of exsolved sulphides;(chalcopyrite +bornite) and (chalcopyrite+ pentlandite+ pyrrhotite). All grains examined are solid solutions of Ru and Os with minor to moderate Ir and Rh (mostly less than 1wt percent, and rarely over 5 wt percent). Arsenic contents vary from 0.4 to 1.3 wt percent and Se from 40 to 620 ppm and the two are correlated. Grains with less Se contain greater amounts of As; [As] = -55 x [Se]+ 16,000 (ppm). The evidence supports their presence at the S site, but the huge departure from 1:1 correlation is not understood. The laurite grains from Borneo are relatively homogeneous, showing rare zoning of Ru and Os. Ratios of S/Se show a narrow spread from 1600 to 2400, which are in the range for sulphides from the shallow, sub-arc mantle (Hattori et al., 2002). The data support their formation in the mantle and subsequent erosion after the obduction of the host ultramafic rocks. The laurite-erlichmanite from Sierra Leone show complicated internal zoning of Ru and Os, as shown pictorially previously (Hattori et al., 1991). The contents of Se and As systematically vary with Ru and Os. The Ru-rich parts (close to laurite composition) are enriched in Se and depleted in As. Furthermore; chalcopyrite inclusions contain even higher Se and lower As than the host laurite/erlichmanite. They show a narrow spread from 1650 to

  3. Allelic and haplotypic diversity at the rp1 rust resistance locus of maize.

    PubMed Central

    Smith, Shavannor M; Pryor, Anthony J; Hulbert, Scot H

    2004-01-01

    The maize Rp1 rust resistance locus is a complex consisting of a family of closely related resistance genes. The number of Rp1 paralogs in different maize lines (haplotypes) varied from a single gene in some stocks of the inbred A188 to >50 genes in haplotypes carrying the Rp1-A and Rp1-H specificities. The sequences of paralogs in unrelated haplotypes differ, indicating that the genetic diversity of Rp1-related genes is extremely broad in maize. Two unrelated haplotypes with five or nine paralogs had identical resistance phenotypes (Rp1-D) encoded in genes that differed by three nucleotides resulting in a single amino acid substitution. Genes in some haplotypes are more similar to each other than to any of the genes in other haplotypes indicating that they are evolving in a concerted fashion. PMID:15342531

  4. Haplotyping germline and cancer genomes with high-throughput linked-read sequencing.

    PubMed

    Zheng, Grace X Y; Lau, Billy T; Schnall-Levin, Michael; Jarosz, Mirna; Bell, John M; Hindson, Christopher M; Kyriazopoulou-Panagiotopoulou, Sofia; Masquelier, Donald A; Merrill, Landon; Terry, Jessica M; Mudivarti, Patrice A; Wyatt, Paul W; Bharadwaj, Rajiv; Makarewicz, Anthony J; Li, Yuan; Belgrader, Phillip; Price, Andrew D; Lowe, Adam J; Marks, Patrick; Vurens, Gerard M; Hardenbol, Paul; Montesclaros, Luz; Luo, Melissa; Greenfield, Lawrence; Wong, Alexander; Birch, David E; Short, Steven W; Bjornson, Keith P; Patel, Pranav; Hopmans, Erik S; Wood, Christina; Kaur, Sukhvinder; Lockwood, Glenn K; Stafford, David; Delaney, Joshua P; Wu, Indira; Ordonez, Heather S; Grimes, Susan M; Greer, Stephanie; Lee, Josephine Y; Belhocine, Kamila; Giorda, Kristina M; Heaton, William H; McDermott, Geoffrey P; Bent, Zachary W; Meschi, Francesca; Kondov, Nikola O; Wilson, Ryan; Bernate, Jorge A; Gauby, Shawn; Kindwall, Alex; Bermejo, Clara; Fehr, Adrian N; Chan, Adrian; Saxonov, Serge; Ness, Kevin D; Hindson, Benjamin J; Ji, Hanlee P

    2016-03-01

    Haplotyping of human chromosomes is a prerequisite for cataloguing the full repertoire of genetic variation. We present a microfluidics-based, linked-read sequencing technology that can phase and haplotype germline and cancer genomes using nanograms of input DNA. This high-throughput platform prepares barcoded libraries for short-read sequencing and computationally reconstructs long-range haplotype and structural variant information. We generate haplotype blocks in a nuclear trio that are concordant with expected inheritance patterns and phase a set of structural variants. We also resolve the structure of the EML4-ALK gene fusion in the NCI-H2228 cancer cell line using phased exome sequencing. Finally, we assign genetic aberrations to specific megabase-scale haplotypes generated from whole-genome sequencing of a primary colorectal adenocarcinoma. This approach resolves haplotype information using up to 100 times less genomic DNA than some methods and enables the accurate detection of structural variants. PMID:26829319

  5. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis

    PubMed Central

    van der Heijden, Roel A.; Bijzet, Johan; Meijers, Wouter C.; Yakala, Gopala K.; Kleemann, Robert; Nguyen, Tri Q.; de Boer, Rudolf A.; Schalkwijk, Casper G.; Hazenberg, Bouke P. C.; Tietge, Uwe J. F.; Heeringa, Peter

    2015-01-01

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process. PMID:26563579

  6. Age-dependent changes in the sphingolipid composition of CD4+ T cell membranes and immune synapses implicate glucosylceramides in age-related T cell dysfunction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sphingolipid (SL4) composition can influence the biophysical properties of cell membranes. Additionally, specific SL modulate signaling pathways involved in proliferation, senescence, and apoptosis. We investigated age-dependent changes in the SL composition of CD4+ T cells, and the impact of these ...

  7. Optimization of forest age-dependent light-use efficiency and its implications on climate-vegetation interactions in china

    NASA Astrophysics Data System (ADS)

    Li, Z.; Zhou, T.

    2015-04-01

    Forest's net primary productivity (NPP) is a key index in studying interactions of climate and vegetation, and accurate prediction of NPP is essential to understand the forests' response to climate change. The magnitude and trends of forest NPP not only depend on climate factors (e.g., temperature and precipitation), but also on the succession stages (i.e., forest stand age). Although forest stand age plays a significant role on NPP, it is usually ignored by remote sensing-based models. In this study, we used remote sensing data and meteorological data to estimate forest NPP in China based on CASA model, and then employed field observations to inversely estimate the parameter of maximum light-use efficiency (ɛmax) of forests in different stand ages. We further developed functions to describe the relationship between maximum light-use efficiency (ɛmax) and forest stand age, and estimated forest age-dependent NPP based on these functions. The results showed that ɛmax has changed according to forest types and the forest stand age. For deciduous broadleaf forest, the average ɛmax of young, middle-aged and mature forest are 0.68, 0.65 and 0.60 gC MJ-1. For evergreen broadleaf forest, the average ɛmax of young, middle-aged and mature forests are 1.05, 1.01 and 0.99 gC MJ-1. For evergreen needleleaf forest, the average ɛmax of young, middle-aged and mature forests are 0.72, 0.57 and 0.52 gC MJ-1.The NPP of young and middle-aged forests were underestimated based on a constant ɛmax. Young forests and middle-aged forests had higher ɛmax, and they were more sensitive to trends and fluctuations of climate change, so they led to greater annual fluctuations of NPP. These findings confirm the importance of considering forest stand age to the estimation of NPP and they are significant to study the response of forests to climate change.

  8. Evidence for an age-dependent influence of environmental variations on a long-lived seabird's life-history traits.

    PubMed

    Pardo, Deborah; Barbraud, Christophe; Authier, Matthieu; Weimerskirch, Henri

    2013-01-01

    Theoretical and empirical studies have highlighted the effects of age on several life-history traits in wild populations. There is also increasing evidence for environmental effects on their demographic traits. However, quantifying how individuals differentially respond to environmental variations according to their age remains a challenge in ecology. In a population of Black-browed Albatrosses monitored during 43 years, we analyzed how life-history traits varied according to age, and whether individuals of different ages responded in different ways to environmental conditions. To do so, we: (1) examined how age affected seven life-history traits, (2) investigated differences in temporal variance of demographic traits between age classes, and (3) tested for age-dependent effects of climate and fisheries covariates on demographic traits. Overall, there was a tendency for traits to improve during the first years of life (5-10 years), to peak and remain stable at middle age (10-30 years), and decline at old ages. At young ages, survival and reproductive parameters increased, except offspring body condition at fledging, suggesting that younger parents had already acquired good foraging capacities. However, they suffered from inexperience in breeding as suggested by their higher breeding failures during incubation. There was evidence for reproductive and actuarial senescence. In particular, breeding success and offspring body condition declined abruptly, suggesting altered foraging capacities of old individuals. Middle-aged individuals had the lowest temporal variance of demographic traits. Although this is predicted by the theory of environmental canalization, it could also results from a higher susceptibility of young and old birds due to their respective inexperience and senescence. The highest temporal variances were found in old individuals. Survival was significantly influenced by sea surface temperatures in the foraging zone of this albatross population during

  9. Aerobic exercise training induces skeletal muscle hypertrophy and age-dependent adaptations in myofiber function in young and older men

    PubMed Central

    Konopka, Adam R.; Undem, Miranda K.; Hinkley, James M.; Minchev, Kiril; Kaminsky, Leonard A.; Trappe, Todd A.; Trappe, Scott

    2012-01-01

    To examine potential age-specific adaptations in skeletal muscle size and myofiber contractile physiology in response to aerobic exercise, seven young (YM; 20 ± 1 yr) and six older men (OM; 74 ± 3 yr) performed 12 wk of cycle ergometer training. Muscle biopsies were obtained from the vastus lateralis to determine size and contractile properties of isolated slow [myosin heavy chain (MHC) I] and fast (MHC IIa) myofibers, MHC composition, and muscle protein concentration. Aerobic capacity was higher (P < 0.05) after training in both YM (16 ± 2%) and OM (13 ± 3%). Quadriceps muscle volume, determined via MRI, was 5 ± 1 and 6 ± 1% greater (P < 0.05) after training for YM and OM, respectively, which was associated with an increase in MHC I myofiber cross-sectional area (CSA), independent of age. MHC I peak power was higher (P < 0.05) after training for both YM and OM, while MHC IIa peak power was increased (P < 0.05) with training in OM only. MHC I and MHC IIa myofiber peak and normalized (peak force/CSA) force were preserved with training in OM, while MHC I peak force/CSA and MHC IIa peak force were lower (P < 0.05) after training in YM. The age-dependent adaptations in myofiber function were not due to changes in protein content, as total muscle protein and myofibrillar protein concentration were unchanged (P > 0.05) with training. Training reduced (P < 0.05) the proportion of MHC IIx isoform, independent of age, whereas no other changes in MHC composition were observed. These data suggest relative improvements in muscle size and aerobic capacity are similar between YM and OM, while adaptations in myofiber contractile function showed a general improvement in OM. Training-related increases in MHC I and MHC IIa peak power reveal that skeletal muscle of OM is responsive to aerobic exercise training and further support the use of aerobic exercise for improving cardiovascular and skeletal muscle health in older individuals. PMID:22984247

  10. Simultaneous age-dependent and age-independent sexual selection in the lekking black grouse (Lyrurus tetrix).

    PubMed

    Kervinen, Matti; Lebigre, Christophe; Soulsbury, Carl D

    2016-05-01

    Individuals' reproductive success is often strongly associated with their age, with typical patterns of early-life reproductive improvement and late-life senescence. These age-related patterns are due to the inherent trade-offs between life-history traits competing for a limited amount of resources available to the organisms. In males, such trade-offs are exacerbated by the resource requirements associated with the expression of costly sexual traits, leading to dynamic changes in trait expression throughout their life span. Due to the age dependency of male phenotypes, the relationship between the expression of male traits and mating success can also vary with male age. Hence, using longitudinal data in a lekking species with strong sexual selection - the black grouse Lyrurus tetrix - we quantified the effects of age, life span and age of first lek attendance (AFL) on male annual mating success (AMS) to separate the effects of within-individual improvement and senescence on AMS from selective (dis)appearance of certain phenotypes. Then, we used male AMS to quantify univariate and multivariate sexual selection gradients on male morphological and behavioural traits with and without accounting for age and age-related effects of other traits. Male AMS increased with age, and there was no significant reproductive senescence. Most males never copulated, and of the ones that did, the majority had only one successful year. Life span was unrelated to AMS, but early AFL tended to lead to higher AMS at ages 1-3. AMS was related to most morphological and behavioural traits when male age was ignored. Accounting for age and age-specific trait effects (i.e. the interaction between a trait and age) reduced the magnitude of the selection gradients and revealed that behavioural traits are under consistent sexual selection, while sexual selection on morphological traits is stronger in old males. Therefore, sexual selection in black grouse operates primarily on male behaviour and

  11. Phenotypic and genetic characterization of a novel phenotype in pigs characterized by juvenile hairlessness and age dependent emphysema

    PubMed Central

    Bruun, Camilla S; Jørgensen, Claus B; Bay, Lene; Cirera, Susanna; Jensen, Henrik E; Leifsson, Páll S; Nielsen, Jens; Christensen, Knud; Fredholm, Merete

    2008-01-01

    Background A pig phenotype characterized by juvenile hairlessness, thin skin and age dependent lung emphysema has been discovered in a Danish pig herd. The trait shows autosomal co-dominant inheritance with all three genotypes distinguishable. Since the phenotype shows resemblance to the integrin β6 -/- knockout phenotype seen in mice, the two genes encoding the two subunits of integrin αvβ6, i.e. ITGB6 and ITGAV, were considered candidate genes for this trait. Results The mutated pig phenotype is characterized by hairlessness until puberty, thin skin with few hair follicles and absence of musculi arrectores pili, and at puberty or later localized areas of emphysema are seen in the lungs. Comparative mapping predicted that the porcine ITGB6 andITGAV orthologs map to SSC15. In an experimental family (n = 113), showing segregation of the trait, the candidate region was confirmed by linkage analysis with four microsatellite markers. Mapping of the porcine ITGB6 and ITGAV in the IMpRH radiation hybrid panel confirmed the comparative mapping information. Sequencing of the ITGB6 and ITGAV coding sequences from affected and normal pigs revealed no evidence of a causative mutation, but alternative splicing of the ITGB6 pre-mRNA was detected. For both ITGB6 and ITGAV quantitative PCR revealed no significant difference in the expression levels in normal and affected animals. In a western blot, ITGB6 was detected in lung protein samples of all three genotypes. This result was supported by flow cytometric analyses which showed comparable reactions of kidney cells from affected and normal pigs with an integrin αvβ6 monoclonal antibody. Also, immunohistochemical staining of lung tissue with an integrin β6 antibody showed immunoreaction in both normal and affected pigs. Conclusion A phenotype resembling the integrin β6 -/- knockout phenotype seen in mice has been characterized in the pig. The candidate region on SSC15 has been confirmed by linkage analysis but molecular

  12. Age-dependent variation in mating success of sterile male Mediterranean fruit flies (Diptera: Tephritidae): implications for sterile insect technique.

    PubMed

    Shelly, Todd E; Edu, James; Pahio, Elaine

    2007-08-01

    The sterile insect technique (SIT) is widely used in integrated programs against the Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae). Unfortunately, the mass-rearing procedures inherent to the SIT often lead to a reduction in the mating ability of the released males. To counter this deficiency, SIT programs rely upon the production and release of large numbers of sterile males to achieve high overflooding (sterile:wild male) ratios. To ensure a high release volume, emergence facilities release adult males at a young age (2 d old in some cases). The primary objective of this study was to describe age-dependent variation in the mating propensity and competitiveness of sterile males of C. capitata. Males that were 2 or 3 d old had lower mating propensity than males that were > or =4 d old, and 3-d-old males had lower mating competitiveness than males that were > or =4 d old. Given these results, we measured the effect of a longer holding period on male mortality in storage boxes. With delayed food placement, males held in storage boxes for 4 d after emergence showed no higher mortality than males held for only 2 d (the standard interval). Using large field enclosures, we compared the levels of egg sterility attained via releases of 2- versus 4-d-old sterile males at two overflooding ratios (5:1 and 100:1). At the lower ratio, the proportion of unhatched eggs observed for trials involving 2-d-old sterile males was not, on average, significantly higher than that observed for matings between wild flies (33 versus 25%, respectively), whereas the level of egg sterility observed for releases of 4 d old sterile males was 62%. At the 100:1 overflooding ratio, the proportion of unhatched eggs associated with the 2-d-old sterile males was 58%, a level not significantly different from that induced by 4-d-old sterile males at the 5:1 ratio and significantly lower than the level (79%) observed for 4-d-old sterile males at 100:1 overflooding ratio

  13. Age-dependent impacts of peatland restoration on the net ecosystem CO2 exchange of blanket bogs in Northern Scotland

    NASA Astrophysics Data System (ADS)

    Hambley, Graham; Hill, Timothy; Saunders, Matthew; Arn Teh, Yit

    2015-04-01

    The Flow Country of Northern Scotland is the largest area of contiguous blanket bog in the UK covering an area in excess of 400 km2. This region is the single largest peat and soil C repository in the UK, and plays a key role in mediating regional atmospheric exchanges of greenhouse gases (GHGs) such as carbon dioxide (CO2), methane (CH4) and water vapour (H2O). However, these peatlands were subject to significant afforestation in the 1980s, where large areas of blanket bog were drained and planted with Sitka spruce (Picea sitchensis) and Lodgepole Pine (Pinus contorta), resulting in modifications to micro-topographic features, vegetation composition and soil properties such as bulk density and water holding capacity, all of which are known to influence the production and emission of key GHGs. Since the late 1990s restoration work has been undertaken to remove forest plantations and to restore the peatland areas by raising the water table, predominantly by drain and furrow blocking, in order to encourage the recolonisation of Sphagnum species. Here we report findings from an eddy covariance study of CO2 and H2O exchange from an unmanaged peatland and a chronosequence of restored peatland sites, which were felled in 1998 and 2004. Located within the Forsinard Flows National Nature Reserve in Northern Scotland, these sites are being studied to better understand the key drivers of carbon dynamics in these ecosystems and also assess the age-dependent impacts of peatland restoration on the net CO2 sink strength. Preliminary data show rates of CO2 uptake increased with time since restoration, with peak assimilation rates of -9.9 and -14.4 micro mol CO2 m-2 s-1 measured at the 10 and 16 year old restoration sites, respectively. Carbon losses through ecosystem respiration followed a similar pattern. The data collected to date indicates that while peatland restoration is actively increasing CO2 uptake at each of the sites, more long-term observational data is required to

  14. Age-dependent inhalation doses to members of the public from indoor short-lived radon progeny.

    PubMed

    Brudecki, K; Li, W B; Meisenberg, O; Tschiersch, J; Hoeschen, C; Oeh, U

    2014-08-01

    The main contribution of radiation dose to the human lungs from natural exposure originates from short-lived radon progeny. In the present work, the inhalation doses from indoor short-lived radon progeny, i.e., (218)Po, (214)Pb, (214)Bi, and (214)Po, to different age groups of members of the public were calculated. In the calculations, the age-dependent systemic biokinetic models of polonium, bismuth, and lead published by the International Commission on Radiological Protection (ICRP) were adopted. In addition, the ICRP human respiratory tract and gastrointestinal tract models were applied to determine the deposition fractions in different regions of the lungs during inhalation and exhalation, and the absorption fractions of radon progeny in the alimentary tract. Based on the calculated contribution of each progeny to equivalent dose and effective dose, the dose conversion factor was estimated, taking into account the unattached fraction of aerosols, attached aerosols in the nucleation, accumulation and coarse modes, and the potential alpha energy concentration fraction in indoor air. It turned out that for each progeny, the equivalent doses to extrathoracic airways and the lungs are greater than those to other organs. The contribution of (214)Po to effective dose is much smaller compared to that of the other short-lived radon progeny and can thus be neglected in the dose assessment. In fact, 90 % of the effective dose from short-lived radon progeny arises from (214)Pb and (214)Bi, while the rest is from (218)Po. The dose conversion factors obtained in the present study are 17 and 18 mSv per working level month (WLM) for adult female and male, respectively. This compares to values ranging from 6 to 20 mSv WLM(-1) calculated by other investigators. The dose coefficients of each radon progeny calculated in the present study can be used to estimate the radiation doses for the population, especially for small children and women, in specific regions of the world

  15. Influence of major histocompatibility haplotype on autoimmune disease varies in different inbred families of chickens.

    PubMed Central

    Bacon, L D; Rose, N R

    1979-01-01

    Three partially inbred substrains of Obese strain chickens were studied for the spontaneous development of autoimmune thyroiditis. The influence of the major histocompatibility complex (B haplotype) was marked in one, less marked but still significant in a second, and barely detectable and transient in a third substrain. These differences in the effect of B haplotype may be due to the overriding action of genes other than those within the B haplotype. PMID:286327

  16. Y-chromosomal STR haplotypes in Central Thai population.

    PubMed

    Siriboonpiputtana, T; Jomsawat, U; Rinthachai, T; Thanakitgosate, J; Shotivaranon, J; Limsuwanachot, N; Polyorat, P; Rerkamnuaychoke, B

    2010-04-01

    12 Y-STR loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS438, DYS439 and DYS437) were typed with PowerPlex Y System (Promega, USA) in a total sample of 501 unrelated males from the central part of Thailand. Allele frequencies and gene diversity for each Y-STR locus were determined. Haplotype diversity from the combined 12 Y-STR loci was 0.9996. The present results can be used as Thai ethnic genetic information resources in routine forensic analysis. PMID:20215020

  17. Analysis of the uncertainties associated with the age-dependent thyroid doses and risk of thyroid cancer due to exposure to {sup 131}I

    SciTech Connect

    Hoffman, F.O.; Apostoaei, A.I.; Nair, S.K.

    1996-06-01

    Effects on the thyroid gland due to exposure to {sup 131}I are currently of interest for ongoing retrospective studies of historical releases in Oak Ridge, Tennessee, and Hanford, Washington. Most of the work to date has been limited to dose estimation. This work focuses on estimating both dose and risk of thyroid cancer to an exposed individual. The age-dependent thyroid dose is calculated using a standard metabolic model for iodine. Updated information on thyroid mass from measurements using modem ultrasound techniques was used. The age-dependent risk is calculated using a linear excess relative risk model. An analysis of uncertainties in dose and risk estimates was performed for an individual in a population characterized by the mass of thyroid, by the iodine metabolic parameters, by the background incidence of thyroid cancer and by the excess relative risk per Gy of absorbed dose. The uncertainty analysis was performed using Monte-Carlo simulation, by considering the age-dependent parameters as random functions. The correlation between the metabolic age-dependent parameters was considered explicitly. Special attention is given to a modifying factor that accounts for the effectiveness of {sup 131}I in inducing thyroid cancer as compared to gamma irradiation, for which most of the excess risk factors are derived. This factor is based on review of recent literature and on informal interviews with outside experts, and thus, the expressed uncertainty is subjective in nature. The paper summarizes the age-dependent dose conversion factors (Sv Bq{sup -1}) and slope factors (risk Bq{sup -1}) as well as the uncertainty associated with them. An analysis that identifies the parameters of dominant importance by their contributions to the overall uncertainty is also included.

  18. The age dependence of T2 relaxation times of N-acetyl aspartate, creatine and choline in the human brain at 3 and 4T.

    PubMed

    Jiru, F; Skoch, A; Wagnerova, D; Dezortova, M; Viskova, J; Profant, O; Syka, J; Hajek, M

    2016-03-01

    Knowledge of the T2 age dependence is of importance for MRS clinical studies involving subject groups with a wide age range. A number of studies have focused on the age dependence of T2 values in the human brain, with rather conflicting results. The aim of this study was to analyze the age dependence of T2 values of N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho) in the human brain using data acquired at 3T and 4T and to assess the influence of the macromolecule (MM) baseline handling on the obtained results. Two distinct groups of young and elderly controls have been measured at 3T (TE = 30-540 ms, 9 young and 11 elderly subjects) and 4T (TE = 10-180 ms, 18 young and 14 elderly subjects) using single-voxel spectroscopy. In addition, MM spectra were measured from two subjects using the inversion-recovery technique at 4T. All spectra were processed with LCModel using basis sets with different MM signals (measured or simulated) and also with MM signals included for a different TE range. Individual estimated T2 values were statistically analyzed using the R programming language for the age dependence of T2 values as well as the influence of the MM baseline handling. A significant decrease of T2 values of NAA and Cr in elderly subjects compared with young subjects was confirmed. The same trend was observed for Cho. Significantly higher T2 values calculated using the measured MM baseline for all studied metabolites at 4T were observed for both young and elderly subjects. To conclude, while the handling of MM and lipid signals may have a significant effect on estimated T2 values, we confirmed the age dependence of T2 values of NAA and Cr and the same trend for Cho in the human brain. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26752593

  19. Ehapp2: Estimate haplotype frequencies from pooled sequencing data with prior database information.

    PubMed

    Cao, Chang-Chang; Sun, Xiao

    2016-08-01

    To reduce the cost of large-scale re-sequencing, multiple individuals are pooled together and sequenced called pooled sequencing. Pooled sequencing could provide a cost-effective alternative to sequencing individuals separately. To facilitate the application of pooled sequencing in haplotype-based diseases association analysis, the critical procedure is to accurately estimate haplotype frequencies from pooled samples. Here we present Ehapp2 for estimating haplotype frequencies from pooled sequencing data by utilizing a database which provides prior information of known haplotypes. We first translate the problem of estimating frequency for each haplotype into finding a sparse solution for a system of linear equations, where the NNREG algorithm is employed to achieve the solution. Simulation experiments reveal that Ehapp2 is robust to sequencing errors and able to estimate the frequencies of haplotypes with less than 3% average relative difference for pooled sequencing of mixture of real Drosophila haplotypes with 50× total coverage even when the sequencing error rate is as high as 0.05. Owing to the strategy that proportions for local haplotypes spanning multiple SNPs are accurately calculated first, Ehapp2 retains excellent estimation for recombinant haplotypes resulting from chromosomal crossover. Comparisons with present methods reveal that Ehapp2 is state-of-the-art for many sequencing study designs and more suitable for current massive parallel sequencing. PMID:27216711

  20. Y-STR haplotypes of Native American populations from the Brazilian Amazon region.

    PubMed

    Palha, Teresinha Jesus Brabo Ferreira; Rodrigues, Elzemar Martins Ribeiro; dos Santos, Sidney Emanuel Batista

    2010-10-01

    The allele and haplotype frequencies of nine Y-STRs (DYS19, DYS389 I, DYS389 II, DYS390, DYS391, DYS392, DYS393, DYS385 I/II) were determined in a sample of six native tribes from the Brazilian Amazon (Tiriyó, Awa-Guajá, Waiãpi, Urubu-Kaapor, Zoé and Parakanã). Forty-eight different haplotypes were identified, 28 of which unique. Five haplotypes are very frequent and were shared by over 10 individuals. The estimated haplotype diversity (0.9114) was very low compared to other geographic groups, including Africans, Europeans and Asians. PMID:20457062

  1. Native and European haplotypes of Phragmites Australis (common reed) in the central Platte River, Nebraska

    USGS Publications Warehouse

    Larson, D.L.; Galatowitsch, S.M.; Larson, J.L.

    2011-01-01

    Phragmites australis (common reed) is known to have occurred along the Platte River historically, but recent rapid increases in both distribution and density have begun to impact habitat for migrating sandhill cranes and nesting piping plovers and least terns. Invasiveness in Phragmites has been associated with the incursion of a European genotype (haplotype M) in other areas; determining the genotype of Phragmites along the central Platte River has implications for proper management of the river system. In 2008 we sampled Phragmites patches along the central Platte River from Lexington to Chapman, NE, stratified by bridge segments, to determine the current distribution of haplotype E (native) and haplotype M genotypes. In addition, we did a retrospective analysis of historical Phragmites collections from the central Platte watershed (1902-2006) at the Bessey Herbarium. Fresh tissue from the 2008 survey and dried tissue from the herbarium specimens were classified as haplotype M or E using the restriction fragment length polymorphism procedure. The European haplotype was predominant in the 2008 samples: only 14 Phragmites shoots were identified as native haplotype E; 224 were non-native haplotype M. The retrospective analysis revealed primarily native haplotype individuals. Only collections made in Lancaster County, near Lincoln, NE, were haplotype M, and the earliest of these was collected in 1973. ?? 2011 Copyright by the Center for Great Plains Studies, University of Nebraska-Lincoln.

  2. Transmission network of the 2014-2015 Ebola epidemic in Sierra Leone.

    PubMed

    Yang, Wan; Zhang, Wenyi; Kargbo, David; Yang, Ruifu; Chen, Yong; Chen, Zeliang; Kamara, Abdul; Kargbo, Brima; Kandula, Sasikiran; Karspeck, Alicia; Liu, Chao; Shaman, Jeffrey

    2015-11-01

    Understanding the growth and spatial expansion of (re)emerging infectious disease outbreaks, such as Ebola and avian influenza, is critical for the effective planning of control measures; however, such efforts are often compromised by data insufficiencies and observational errors. Here, we develop a spatial-temporal inference methodology using a modified network model in conjunction with the ensemble adjustment Kalman filter, a Bayesian inference method equipped to handle observational errors. The combined method is capable of revealing the spatial-temporal progression of infectious disease, while requiring only limited, readily compiled data. We use this method to reconstruct the transmission network of the 2014-2015 Ebola epidemic in Sierra Leone and identify source and sink regions. Our inference suggests that, in Sierra Leone, transmission within the network introduced Ebola to neighbouring districts and initiated self-sustaining local epidemics; two of the more populous and connected districts, Kenema and Port Loko, facilitated two independent transmission pathways. Epidemic intensity differed by district, was highly correlated with population size (r = 0.76, p = 0.0015) and a critical window of opportunity for containing local Ebola epidemics at the source (ca one month) existed. This novel methodology can be used to help identify and contain the spatial expansion of future (re)emerging infectious disease outbreaks. PMID:26559683

  3. Habitat Preferences of Butterflies in the Bumbuna Forest, Northern Sierra Leone

    PubMed Central

    Sundufu, Abu James; Dumbuya, Rashida

    2008-01-01

    The habitat preferences of the butterfly fauna were studied in the Bumbuna Forest Reserve in northern Sierra Leone. The intact forest reserve and a secondary forest regrowth, disturbed as a result of slash-and-burn agriculture, were compared to savanna habitats. Of the 290 specimens collected, 195 butterfly species were included, of which significant proportion were Nymphalidae. Of the 147 forest species, 111 (75.5%) showed preferences for the forest habitats, while 70 (47.6%) and 34 (23.1%) preferred disturbed and savannah habitats, respectively. Numerically, a comparable proportion of savannah species were recorded in the 18 disturbed (73.9%) and 16 savannah habitats (63.2%). Accumulated species richness and diversity indices were lower in the disturbed habitats compared to the forest reserve, but lowest in the savanna habitats. However, a large proportion of forest species, especially those with either a more restricted geographic range or species for which no information on geographic distribution was available, were exclusively captured in the forest patches. The survey indicated the presence of a rich butterfly fauna, which should be systematically collected for further research and study in order to build a good taxonomic database for Sierra Leone. PMID:20302525

  4. Technical efficiency of primary health units in Kailahun and Kenema districts of Sierra Leone

    PubMed Central

    2011-01-01

    Background The objectives of the study reported in this paper were to (i) estimate the technical efficiency of samples of community health centres (CHCs), community health posts (CHPs) and maternal and child health posts (MCHPs) in Kailahun and Kenema districts of Sierra Leone, (ii) estimate the output increases needed to make inefficient MCHPs, CHCs and CHPs efficient, and (iii) explore strategies for increasing technical efficiency of these institutions. Methods This study applies the data envelopment analysis (DEA) approach to analyse technical efficiency of random samples of 36 MCHPs, 22 CHCs and 21 CHPs using input and output data for 2008. Results The findings indicate that 77.8% of the MCHPs, 59.1% of the CHCs and 66.7% of the CHPs were variable returns to scale technically inefficient. The average variable returns to scale technical efficiency was 68.2% (SD = 27.2) among the MCHPs, 69.2% (SD = 33.2) among the CHCs and 59% (SD = 34.7) among the CHPs. Conclusion This study reveals significant technical inefficiencies in the use of health system resources among peripheral health units in Kailahun and Kenema districts of Sierra Leone. There is need to strengthen national and district health information systems to routinely track the quantities and prices of resources injected into the health care systems and health service outcomes (indicators of coverage, quality and health status) to facilitate regular efficiency analyses. PMID:21569339

  5. Assessing biodiversity in Nuevo Leon, Mexico: Are nature reserves the answer?

    USGS Publications Warehouse

    Cantu, C.; Wright, R.G.; Scott, J.M.; Strand, Espen

    2004-01-01

    The Mexican state of Nuevo Leon, located in the northeastern portion of the country, currently has 26 state and three federal nature reserves covering approximately 4.5% of its land area. These reserves were established for a variety of reasons not necessarily related to conservation purposes. In 2000 in response to a growing concern about the lack of organized conservation reserve planning to protect the important biological and physical features of Mexico, the Mexican Commission for Knowledge and Use of Biodiversity proposed 12 new terrestrial reserves for Nuevo Leon. The new reserves, if established, would increase the proportion of protected lands in the state to almost 24% of the state's land area. We compiled a Geographic Information System (GIS) analysis using digital thematic maps of physical and ecological features to examine how well the existing and proposed reserves incorporated the major biological and physical features of the state. The existing reserves are located primarily in regions with elevations > 1,000-1,500 m, on less productive soils, and are dominated by pine and oak forest cover types. As a result, the state's dominant biotic region - low elevation coastal plain with xeric scrub vegetation - is disproportionately under represented in the current reserve system. The new reserves would expand the protection of biophysical resources throughout the state. However, the inclusion of important resources in the low elevation coastal lands would still be limited.

  6. Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone

    PubMed Central

    Park, Daniel J.; Dudas, Gytis; Wohl, Shirlee; Goba, Augustine; Whitmer, Shannon L.M.; Andersen, Kristian G.; Sealfon, Rachel S.; Ladner, Jason T.; Kugelman, Jeffrey R.; Matranga, Christian B.; Winnicki, Sarah M.; Qu, James; Gire, Stephen K.; Gladden-Young, Adrianne; Jalloh, Simbirie; Nosamiefan, Dolo; Yozwiak, Nathan L.; Moses, Lina M.; Jiang, Pan-Pan; Lin, Aaron E.; Schaffner, Stephen F.; Bird, Brian; Towner, Jonathan; Mamoh, Mambu; Gbakie, Michael; Kanneh, Lansana; Kargbo, David; Massally, James L.B.; Kamara, Fatima K.; Konuwa, Edwin; Sellu, Josephine; Jalloh, Abdul A.; Mustapha, Ibrahim; Foday, Momoh; Yillah, Mohamed; Erickson, Bobbie R.; Sealy, Tara; Blau, Dianna; Paddock, Christopher; Brault, Aaron; Amman, Brian; Basile, Jane; Bearden, Scott; Belser, Jessica; Bergeron, Eric; Campbell, Shelley; Chakrabarti, Ayan; Dodd, Kimberly; Flint, Mike; Gibbons, Aridth; Goodman, Christin; Klena, John; McMullan, Laura; Morgan, Laura; Russell, Brandy; Salzer, Johanna; Sanchez, Angela; Wang, David; Jungreis, Irwin; Tomkins-Tinch, Christopher; Kislyuk, Andrey; Lin, Michael F.; Chapman, Sinead; MacInnis, Bronwyn; Matthews, Ashley; Bochicchio, James; Hensley, Lisa E.; Kuhn, Jens H.; Nusbaum, Chad; Schieffelin, John S.; Birren, Bruce W.; Forget, Marc; Nichol, Stuart T.; Palacios, Gustavo F.; Ndiaye, Daouda; Happi, Christian; Gevao, Sahr M.; Vandi, Mohamed A.; Kargbo, Brima; Holmes, Edward C.; Bedford, Trevor; Gnirke, Andreas; Ströher, Ute; Rambaut, Andrew; Garry, Robert F.; Sabeti, Pardis C.

    2015-01-01

    Summary The 2013–2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission. PMID:26091036

  7. Inference and forecast of the current west african ebola outbreak in Guinea, sierra leone and liberia.

    PubMed

    Shaman, Jeffrey; Yang, Wan; Kandula, Sasikiran

    2014-01-01

    The current West African Ebola outbreak poses an unprecedented public health challenge for the world at large. The response of the global community to the epidemic, including deployment of nurses, doctors, epidemiologists, beds, supplies and security, is shaped by our understanding of the spatial-temporal extent and progression of the disease. Ongoing evaluation of the epidemiological characteristics and future course of the Ebola outbreak is needed to stay abreast of any changes to its transmission dynamics, as well as the success or failure of intervention efforts. Here we use observations, dynamic modeling and Bayesian inference to generate simulations and weekly forecasts of the outbreaks in Guinea, Liberia and Sierra Leone. Estimates of key epidemiological characteristics over time indicate continued epidemic growth in West Africa, though there is some evidence of slowing growth in Liberia. 6-week forecasts over successive weeks corroborate these findings; forecasts projecting no future change in intervention efficacy have been more accurate for Guinea and Sierra Leone, but have overestimated incidence and mortality for Liberia. PMID:25642378

  8. Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone.

    PubMed

    Park, Daniel J; Dudas, Gytis; Wohl, Shirlee; Goba, Augustine; Whitmer, Shannon L M; Andersen, Kristian G; Sealfon, Rachel S; Ladner, Jason T; Kugelman, Jeffrey R; Matranga, Christian B; Winnicki, Sarah M; Qu, James; Gire, Stephen K; Gladden-Young, Adrianne; Jalloh, Simbirie; Nosamiefan, Dolo; Yozwiak, Nathan L; Moses, Lina M; Jiang, Pan-Pan; Lin, Aaron E; Schaffner, Stephen F; Bird, Brian; Towner, Jonathan; Mamoh, Mambu; Gbakie, Michael; Kanneh, Lansana; Kargbo, David; Massally, James L B; Kamara, Fatima K; Konuwa, Edwin; Sellu, Josephine; Jalloh, Abdul A; Mustapha, Ibrahim; Foday, Momoh; Yillah, Mohamed; Erickson, Bobbie R; Sealy, Tara; Blau, Dianna; Paddock, Christopher; Brault, Aaron; Amman, Brian; Basile, Jane; Bearden, Scott; Belser, Jessica; Bergeron, Eric; Campbell, Shelley; Chakrabarti, Ayan; Dodd, Kimberly; Flint, Mike; Gibbons, Aridth; Goodman, Christin; Klena, John; McMullan, Laura; Morgan, Laura; Russell, Brandy; Salzer, Johanna; Sanchez, Angela; Wang, David; Jungreis, Irwin; Tomkins-Tinch, Christopher; Kislyuk, Andrey; Lin, Michael F; Chapman, Sinead; MacInnis, Bronwyn; Matthews, Ashley; Bochicchio, James; Hensley, Lisa E; Kuhn, Jens H; Nusbaum, Chad; Schieffelin, John S; Birren, Bruce W; Forget, Marc; Nichol, Stuart T; Palacios, Gustavo F; Ndiaye, Daouda; Happi, Christian; Gevao, Sahr M; Vandi, Mohamed A; Kargbo, Brima; Holmes, Edward C; Bedford, Trevor; Gnirke, Andreas; Ströher, Ute; Rambaut, Andrew; Garry, Robert F; Sabeti, Pardis C

    2015-06-18

    The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission. PMID:26091036

  9. Habitat preferences of butterflies in the Bumbuna Forest, Northern Sierra Leone.

    PubMed

    Sundufu, Abu James; Dumbuya, Rashida

    2008-01-01

    The habitat preferences of the butterfly fauna were studied in the Bumbuna Forest Reserve in northern Sierra Leone. The intact forest reserve and a secondary forest regrowth, disturbed as a result of slash-and-burn agriculture, were compared to savanna habitats. Of the 290 specimens collected, 195 butterfly species were included, of which significant proportion were Nymphalidae. Of the 147 forest species, 111 (75.5%) showed preferences for the forest habitats, while 70 (47.6%) and 34 (23.1%) preferred disturbed and savannah habitats, respectively. Numerically, a comparable proportion of savannah species were recorded in the 18 disturbed (73.9%) and 16 savannah habitats (63.2%). Accumulated species richness and diversity indices were lower in the disturbed habitats compared to the forest reserve, but lowest in the savanna habitats. However, a large proportion of forest species, especially those with either a more restricted geographic range or species for which no information on geographic distribution was available, were exclusively captured in the forest patches. The survey indicated the presence of a rich butterfly fauna, which should be systematically collected for further research and study in order to build a good taxonomic database for Sierra Leone. PMID:20302525

  10. Mining and environmental change in Sierra Leone, West Africa: a remote sensing and hydrogeomorphological study.

    PubMed

    Akiwumi, Fenda A; Butler, David R

    2008-07-01

    This paper evaluates the environmental changes in southwestern Sierra Leone, West Africa from rutile (titanium dioxide) between 1967 and 1995. Mining in peripheral parts of the world economy is a consequence of larger global economic interests. Historically, long-distance trade and export production of minerals and other natural resources primarily for the benefit of core countries are responsible for transforming the natural environment and landscapes of peripheral sectors of the world economy. Tracking environmental change in developing countries such as Sierra Leone is challenging because of financial and infrastructural constraints on the use of ground methods of evaluation and monitoring. Remote sensing data are invaluable in assessing the human dimensions of Land Use and Land Cover Change (LULCC) with implications for political ecology. Using available multi-date infrared Landsat images supplemented with field hydrological and biophysical data, we monitored the rapid temporal and spatial dynamic characteristic of mining areas in the study area with a focus on physical changes to the landscape. Reservoir construction for mining has caused flooding of alluvial lowlands, deforestation, and the creation of tailings and stockpiles over mined-out portions of the lease. Although the study was conducted at a local scale, it represents the broad, regional, past-to-present manner by which global economic interests exploit natural resources and impact the environment in distant places. PMID:17882524

  11. Factors Underlying Ebola Virus Infection Among Health Workers, Kenema, Sierra Leone, 2014–2015

    PubMed Central

    Senga, Mikiko; Pringle, Kimberly; Ramsay, Andrew; Brett-Major, David M.; Fowler, Robert A.; French, Issa; Vandi, Mohamed; Sellu, Josephine; Pratt, Christian; Saidu, Josephine; Shindo, Nahoko; Bausch, Daniel G.

    2016-01-01

    Background. Ebola virus disease (EVD) in health workers (HWs) has been a major challenge during the 2014–2015 outbreak. We examined factors associated with Ebola virus exposure and mortality in HWs in Kenema District, Sierra Leone. Methods. We analyzed data from the Sierra Leone National Viral Hemorrhagic Fever Database, contact tracing records, Kenema Government Hospital (KGH) staff and Ebola Treatment Unit (ETU) rosters, and burial logs. Results. From May 2014 through January 2015, 600 cases of EVD originated in Kenema District, including 92 (15%) HWs, 66 (72%) of whom worked at KGH. Among KGH medical staff and international volunteers, 18 of 62 (29%) who worked in the ETU developed EVD, compared with 48 of 83 (58%) who worked elsewhere in the hospital. Thirteen percent of HWs with EVD reported contact with EVD patients, while 27% reported contact with other infected HWs. The number of HW EVD cases at KGH declined roughly 1 month after implementation of a new triage system at KGH and the opening of a second ETU within the district. The case fatality ratio for HWs and non-HWs with EVD was 69% and 74%, respectively. Conclusions. The cluster of HW EVD cases in Kenema District is one of the largest ever reported. Most HWs with EVD had potential virus exposure both inside and outside of hospitals. Prevention measures for HWs must address a spectrum of infection risks in both formal and informal care settings as well as in the community. PMID:27193749

  12. Learning Styles and Attitudes toward Online Education in Four Universities in the State of Nuevo Leon, Mexico

    ERIC Educational Resources Information Center

    Martinez de Monarrez, Patricia; Korniejczuk, Victor

    2013-01-01

    The purpose of this research was to find the relation-ship between the predominant learning styles among university online students and their attitude toward online education. Data were collected from 385 students enrolled in undergraduate and graduate programs from four universities in the state of Nuevo Leon, Mexico. Significant effects of…

  13. An Examination of Primary School Attendance and Completion among Secondary School Age Adolescents in Post-Conflict Sierra Leone

    ERIC Educational Resources Information Center

    Moyi, Peter

    2013-01-01

    Sierra Leone was ravaged by a civil war between 1991 and 2002. Since the end of the war, it has witnessed an unprecedented increase in school enrollments. Although school enrollment has increased, the number of school age children who are out of school remains high. The focus of international agencies is on children of primary school age, yet a…

  14. Food Deserts in Leon County, FL: Disparate Distribution of Supplemental Nutrition Assistance Program-Accepting Stores by Neighborhood Characteristics

    ERIC Educational Resources Information Center

    Rigby, Samantha; Leone, Angela F.; Kim, Hwahwan; Betterley, Connie; Johnson, Mary Ann; Kurtz, Hilda; Lee, Jung Sun

    2012-01-01

    Objective: Examine whether neighborhood characteristics of racial composition, income, and rurality were related to distribution of Supplemental Nutrition Assistance Program (SNAP)-accepting stores in Leon County, Florida. Design: Cross-sectional; neighborhood and food store data collected in 2008. Setting and Participants: Forty-eight census…

  15. Rural-Urban Migration in Sierra Leone: Determinants and Policy Implications. African Rural Economy Paper No. 13.

    ERIC Educational Resources Information Center

    Byerlee, Derek; And Others

    Study objectives were to: increase the understanding of rural to urban migration processes in Africa and Sierra Leone; develop and test a theoretical schema and survey methodology for migration research; and evaluate the effects of policy on migration. The migration survey was conducted in rural areas, urban areas, and again in the rural areas…

  16. Lymphedema in a 7-year-old boy infected with Wuchereria bancrofti in Sierra Leone: a case report.

    PubMed

    Dome, Mackenzie; Ansumana, Rashid; Covington, Andrea L; Rebollo, Maria P; Sesay, Santigie; Jacobsen, Kathryn H; de Souza, Dziedzom K; Koudou, Benjamin G; Michael, Edwin; Bockarie, Moses J

    2014-06-01

    We present a case of congenital lymphedema in a 7-year-old boy in Sierra Leone with active filarial infection and penile edema. The genital edema with onset at 6 months of age may have been due to a congenital abnormality in lymphatic drainage. Other possible causes of childhood lymphedema, including Milroy's disease, are discussed. PMID:24561072

  17. Mother Tongue Education and Transitional Literacy in Sierra Leone: Prospects and Challenges in the 21st Century.

    ERIC Educational Resources Information Center

    Kamanda, Mohamed Combo

    2002-01-01

    Discusses the historical perspective relating to current problems facing mother tongue instruction in Sierra Leone and examines post-independence policies to highlight the institutional bases of mother tongue education and to consider causes of inertia and negative attitudes towards it since independence. (Author/VWL)

  18. Environmental Scan on Education in Sierra Leone with Particular Reference to Open and Distance Learning and Information and Communication Technologies

    ERIC Educational Resources Information Center

    Alghali, A.M.; Turay, Edward D.A.; Thompson, Ekundayo J.D.; Kandeh, Joseph B.A.

    2005-01-01

    The Sierra Leone National Education Master Plan 1997-2006 deals with all aspects of the formal and non-formal sectors of the education system, providing support for basic education, education for the physically challenged, disadvantaged and gifted learners, women and girls' education, technical/vocational and science education, tertiary education,…

  19. The Fear of Poisoning and the Management of Urban Social Relations among the Professional Group in Freetown, Sierra Leone.

    ERIC Educational Resources Information Center

    Harrell-Bond, B. E.

    1978-01-01

    Social relationships among professionals in Sierra Leone are marked by competition and tension. An examination of food symbolism, patterns of food sharing, and attitudes toward the safety of accepted proffered food and drink provides a means of looking at how the professionals structure and manage their social relations. (Author/EB)

  20. Molecular Signature of the Ebola Virus Associated with the Fishermen Community Outbreak in Aberdeen, Sierra Leone, in February 2015

    PubMed Central

    Gruber, Cesare E. M.; Carletti, Fabrizio; Meschi, Silvia; Castilletti, Concetta; Vairo, Francesco; Biava, Mirella; Minosse, Claudia; Strada, Gino; Portella, Gina; Miccio, Rossella; Minardi, Valeria; Rolla, Luca; Kamara, Abdul; Chillemi, Giovanni; Desideri, Alessandro; Di Caro, Antonino; Ippolito, Giuseppe

    2015-01-01

    We report the complete genome sequence of Ebola virus from a health worker linked to a cluster of cases occurring in the fishing community of Aberdeen, Sierra Leone (February 2015), which were characterized by unusually severe presentation. The sequence, clustering in the SL subclade 3.2.4, harbors mutations potentially relevant for pathogenesis. PMID:26404609

  1. Examining Internet Usage Demographic Differences and the Relationship between Internet Usage and Business Outcomes in Sierra Leone

    ERIC Educational Resources Information Center

    Kamara, Mohamed K.

    2013-01-01

    This study utilized the unified theory of acceptance and use of technology (UTAUT) to determine Internet users' perceptions and behavioral intentions to accept Wi-Fi technology deployment in Sierra Leone. The study sought to investigate (a) the Internet usage rates before and after Wi-Fi adaption in Freetown; (b) differences in Internet usage…

  2. Use of the FilmArray System for Detection of Zaire ebolavirus in a Small Hospital in Bo, Sierra Leone

    PubMed Central

    Ansumana, Rashid; Taitt, Chris R.; Lamin, Joseph M.; Bangura, Umaru; Lahai, Joseph; Mbayo, George; Kanneh, Mohamed B.; Bawo, Ben; Bockarie, Alfred S.; Scullion, Matt; Phillips, Cynthia L.; Horner, Cynthia P.; Jacobsen, Kathryn H.; Stenger, David A.

    2015-01-01

    Laboratories associated with small hospitals often have limited expertise, personnel, and equipment to rapidly identify rare and emerging infectious diseases. We describe the successful use of the FilmArray system for rapid detection of Ebola virus directly from clinical samples in 6 out of 83 tested subjects in a small health care center in Sierra Leone. PMID:25972415

  3. Use of the FilmArray System for Detection of Zaire ebolavirus in a Small Hospital in Bo, Sierra Leone.

    PubMed

    Leski, Tomasz A; Ansumana, Rashid; Taitt, Chris R; Lamin, Joseph M; Bangura, Umaru; Lahai, Joseph; Mbayo, George; Kanneh, Mohamed B; Bawo, Ben; Bockarie, Alfred S; Scullion, Matt; Phillips, Cynthia L; Horner, Cynthia P; Jacobsen, Kathryn H; Stenger, David A

    2015-07-01

    Laboratories associated with small hospitals often have limited expertise, personnel, and equipment to rapidly identify rare and emerging infectious diseases. We describe the successful use of the FilmArray system for rapid detection of Ebola virus directly from clinical samples in 6 out of 83 tested subjects in a small health care center in Sierra Leone. PMID:25972415

  4. A Comprehensive Vocational Education Program for Career Development in Leon County. Final Report. Volume 1. Program Performance Report.

    ERIC Educational Resources Information Center

    Leon County Schools, Tallahassee, FL.

    The document presents an account of project activities that evolved around the development and implementation of career education in Leon County School District, Florida. The purpose of the project was to begin effecting needed educational changes at the K-14 level by developing a comprehensive career education program designed to increase student…

  5. Haplotypes and Sequence Variation in the Ovine Adiponectin Gene (ADIPOQ)

    PubMed Central

    An, Qing-Ming; Zhou, Hui-Tong; Hu, Jiang; Luo, Yu-Zhu; Hickford, Jon G. H.

    2015-01-01

    The adiponectin gene (ADIPOQ) plays an important role in energy homeostasis. In this study five separate regions (regions 1 to 5) of ovine ADIPOQ were analysed using PCR-SSCP. Four different PCR-SSCP patterns (A1-D1, A2-D2) were detected in region-1 and region-2, respectively, with seven and six SNPs being revealed. In region-3, three different patterns (A3-C3) and three SNPs were observed. Two patterns (A4-B4, A5-B5) and two and one SNPs were observed in region-4 and region-5, respectively. In total, nineteen SNPs were detected, with five of them in the coding region and two (c.46T/C and c.515G/A) putatively resulting in amino acid changes (p.Tyr16His and p.Lys172Arg). In region-1, -2 and -3 of 316 sheep from eight New Zealand breeds, variants A1, A2 and A3 were the most common, although variant frequencies differed in the eight breeds. Across region-1 and region-3, nine haplotypes were identified and haplotypes A1-A3, A1-C3, B1-A3 and B1-C3 were most common. These results indicate that the ADIPOQ gene is polymorphic and suggest that further analysis is required to see if the variation in the gene is associated with animal production traits. PMID:26610572

  6. A haplotype framework for cystic fibrosis mutations in Iran.

    PubMed

    Elahi, Elahe; Khodadad, Ahmad; Kupershmidt, Ilya; Ghasemi, Fereshteh; Alinasab, Babak; Naghizadeh, Ramin; Eason, Robert G; Amini, Mahshid; Esmaili, Mehran; Esmaeili Dooki, Mohammad R; Sanati, Mohammad H; Davis, Ronald W; Ronaghi, Mostafa; Thorstenson, Yvonne R

    2006-02-01

    This is the first comprehensive profile of cystic fibrosis transmembrane conductance regulator (CFTR) mutations and their corresponding haplotypes in the Iranian population. All of the 27 CFTR exons of 60 unrelated Iranian CF patients were sequenced to identify disease-causing mutations. Eleven core haplotypes of CFTR were identified by genotyping six high-frequency simple nucleotide polymorphisms. The carrier frequency of 2.5 in 100 (1 in 40) was estimated from the frequency of heterozygous patients and suggests that contrary to popular belief, cystic fibrosis may be a common, under-diagnosed disease in Iran. A heterogeneous mutation spectrum was observed at the CFTR locus in 60 cystic fibrosis (CF) patients from Iran. Twenty putative disease-causing mutations were identified on 64 (53%) of the 120 chromosomes. The five most common Iranian mutations together represented 37% of the expected mutated alleles. The most frequent mutation, DeltaF508 (p.F508del), represented only 16% of the expected mutated alleles. The next most frequent mutations were c.1677del2 (p.515fs) at 7.5%, c.4041C>G (p.N1303K) at 5.6%, c.2183AA>G (p.684fs) at 5%, and c.3661A>T (p.K1177X) at 2.5%. Three of the five most frequent Iranian mutations are not included in a commonly used panel of CF mutations, underscoring the importance of identifying geographic-specific mutations in this population. PMID:16436643

  7. A Haplotype Framework for Cystic Fibrosis Mutations in Iran

    PubMed Central

    Elahi, Elahe; Khodadad, Ahmad; Kupershmidt, Ilya; Ghasemi, Fereshteh; Alinasab, Babak; Naghizadeh, Ramin; Eason, Robert G.; Amini, Mahshid; Esmaili, Mehran; Esmaeili Dooki, Mohammad R.; Sanati, Mohammad H.; Davis, Ronald W.; Ronaghi, Mostafa; Thorstenson, Yvonne R.

    2006-01-01

    This is the first comprehensive profile of cystic fibrosis transmembrane conductance regulator (CFTR) mutations and their corresponding haplotypes in the Iranian population. All of the 27 CFTR exons of 60 unrelated Iranian CF patients were sequenced to identify disease-causing mutations. Eleven core haplotypes of CFTR were identified by genotyping six high-frequency simple nucleotide polymorphisms. The carrier frequency of 2.5 in 100 (1 in 40) was estimated from the frequency of heterozygous patients and suggests that contrary to popular belief, cystic fibrosis may be a common, under-diagnosed disease in Iran. A heterogeneous mutation spectrum was observed at the CFTR locus in 60 cystic fibrosis (CF) patients from Iran. Twenty putative disease-causing mutations were identified on 64 (53%) of the 120 chromosomes. The five most common Iranian mutations together represented 37% of the expected mutated alleles. The most frequent mutation, ΔF508 (p.F508del), represented only 16% of the expected mutated alleles. The next most frequent mutations were c.1677del2 (p.515fs) at 7.5%, c.4041C>G (p.N1303K) at 5.6%, c.2183AA>G (p.684fs) at 5%, and c.3661A>T (p.K1177X) at 2.5%. Three of the five most frequent Iranian mutations are not included in a commonly used panel of CF mutations, underscoring the importance of identifying geographic-specific mutations in this population. PMID:16436643

  8. Mitochondrial haplotypes associated with biomarkers for Alzheimer's disease.

    PubMed

    Ridge, Perry G; Koop, Andre; Maxwell, Taylor J; Bailey, Matthew H; Swerdlow, Russell H; Kauwe, John S K; Honea, Robyn A

    2013-01-01

    Various studies have suggested that the mitochondrial genome plays a role in late-onset Alzheimer's disease, although results are mixed. We used an endophenotype-based approach to further characterize mitochondrial genetic variation and its relationship to risk markers for Alzheimer's disease. We analyzed longitudinal data from non-demented, mild cognitive impairment, and late-onset Alzheimer's disease participants in the Alzheimer's Disease Neuroimaging Initiative with genetic, brain imaging, and behavioral data. We assessed the relationship of structural MRI and cognitive biomarkers with mitochondrial genome variation using TreeScanning, a haplotype-based approach that concentrates statistical power by analyzing evolutionarily meaningful groups (or clades) of haplotypes together for association with a phenotype. Four clades were associated with three different endophenotypes: whole brain volume, percent change in temporal pole thickness, and left hippocampal atrophy over two years. This is the first study of its kind to identify mitochondrial variation associated with brain imaging endophenotypes of Alzheimer's disease. Our results provide additional evidence that the mitochondrial genome plays a role in risk for Alzheimer's disease. PMID:24040196

  9. HLA Type Inference via Haplotypes Identical by Descent

    NASA Astrophysics Data System (ADS)

    Setty, Manu N.; Gusev, Alexander; Pe'Er, Itsik

    The Human Leukocyte Antigen (HLA) genes play a major role in adaptive immune response and are used to differentiate self antigens from non self ones. HLA genes are hyper variable with nearly every locus harboring over a dozen alleles. This variation plays an important role in susceptibility to multiple autoimmune diseases and needs to be matched on for organ transplantation. Unfortunately, HLA typing by serological methods is time consuming and expensive compared to high throughput Single Nucleotide Polymorphism (SNP) data. We present a new computational method to infer per-locus HLA types using shared segments Identical By Descent (IBD), inferred from SNP genotype data. IBD information is modeled as graph where shared haplotypes are explored among clusters of individuals with known and unknown HLA types to identify the latter. We analyze performance of the method in a previously typed subset of the HapMap population, achieving accuracy of 96% in HLA-A, 94% in HLA-B, 95% in HLA-C, 77% in HLA-DR1, 93% in HLA-DQA1 and 90% in HLA-DQB1 genes. We compare our method to a tag SNP based approach and demonstrate higher sensitivity and specificity. Our method demonstrates the power of using shared haplotype segments for large-scale imputation at the HLA locus.

  10. Chronic inflammatory state in sickle cell anemia patients is associated with HBB(*)S haplotype.

    PubMed

    Bandeira, Izabel C J; Rocha, Lillianne B S; Barbosa, Maritza C; Elias, Darcielle B D; Querioz, José A N; Freitas, Max Vitor Carioca; Gonçalves, Romélia P

    2014-02-01

    The chronic inflammatory state in sickle cell anemia (SCA) is associated with several factors such as the following: endothelial damage; increased production of reactive oxygen species; hemolysis; increased expression of adhesion molecules by leukocytes, erythrocytes, and platelets; and increased production of proinflammatory cytokines. Genetic characteristics affecting the clinical severity of SCA include variations in the hemoglobin F (HbF) level, coexistence of alpha-thalassemia, and the haplotype associated with the HbS gene. The different haplotypes of SCA are Bantu, Benin, Senegal, Cameroon, and Arab-Indian. These haplotypes are associated with ethnic groups and also based on the geographical origin. Studies have shown that the Bantu haplotype is associated with higher incidence of clinical complications than the other haplotypes and is therefore considered to have the worst prognosis. This study aimed to evaluate the profile of the proinflammatory cytokines interleukin-6, tumor necrosis factor-α, and interleukin-17 in patients with SCA and also to assess the haplotypes associated with beta globin cluster S (HBB(*)S). We analyzed a total of 62 patients who had SCA and had been treated with hydroxyurea; they had received a dose ranging between 15 and 25 (20.0±0.6)mg/kg/day for 6-60 (18±3.4)months; their data were compared with those for 30 normal individuals. The presence of HbS was detected and the haplotypes of the beta S gene cluster were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our study demonstrated that SCA patients have increased inflammatory profile when compared to the healthy individuals. Further, analysis of the association between the haplotypes and inflammatory profile showed that the levels of IL-6 and TNF-α were greater in subjects with the Bantu/Bantu haplotype than in subjects with the Benin/Benin haplotype. The Bantu/Benin haplotype individuals had lower levels of cytokines than those with

  11. Kullback-Leibler divergence for detection of rare haplotype common disease association.

    PubMed

    Lin, Shili

    2015-11-01

    Rare haplotypes may tag rare causal variants of common diseases; hence, detection of such rare haplotypes may also contribute to our understanding of complex disease etiology. Because rare haplotypes frequently result from common single-nucleotide polymorphisms (SNPs), focusing on rare haplotypes is much more economical compared with using rare single-nucleotide variants (SNVs) from sequencing, as SNPs are available and 'free' from already amassed genome-wide studies. Further, associated haplotypes may shed light on the underlying disease causal mechanism, a feat unmatched by SNV-based collapsing methods. In recent years, data mining approaches have been adapted to detect rare haplotype association. However, as they rely on an assumed underlying disease model and require the specification of a null haplotype, results can be erroneous if such assumptions are violated. In this paper, we present a haplotype association method based on Kullback-Leibler divergence (hapKL) for case-control samples. The idea is to compare haplotype frequencies for the cases versus the controls by computing symmetrical divergence measures. An important property of such measures is that both the frequencies and logarithms of the frequencies contribute in parallel, thus balancing the contributions from rare and common, and accommodating both deleterious and protective, haplotypes. A simulation study under various scenarios shows that hapKL has well-controlled type I error rates and good power compared with existing data mining methods. Application of hapKL to age-related macular degeneration (AMD) shows a strong association of the complement factor H (CFH) gene with AMD, identifying several individual rare haplotypes with strong signals. PMID:25735482

  12. Involvement of Prx3, a Drosophila ortholog of the thiol-dependent peroxidase PRDX3, in age-dependent oxidative stress resistance.

    PubMed

    Kayashima, Yasunari; Yamakawa-Kobayashi, Kimiko

    2012-01-01

    Peroxiredoxins (Prxs) are a family of multifunctional antioxidant thioredoxin-dependent peroxidases. We used Drosophila melanogaster to examine the function of Prx3, the Drosophila homolog of human PRDX3. The oxidative stress response in adult Drosophila is age-dependent. RNAiinduced Prx3 knockdown in adult flies did not change their phenotype in normal conditions, but they had a shorter survival than the Prx3(+) controls in the presence of H2O2. The expression levels of the Prx3 were reduced by aging. These results suggest that Prx3 plays an important role in the oxidative stress response and is involved in the age-dependent competence of the oxidative stress response. PMID:23124252

  13. Performance of single nucleotide polymorphisms versus haplotypes for genome-wide association analysis in barley

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genome-wide association studies (GWAS) may benefit from using haplotype information for making marker-phenotype associations. Several rationales for grouping single nucleotide polymorphisms (SNPs) into haplotype blocks exist, but any advantage may depend on the genetic architecture of traits, patter...

  14. Use of Haplotypes to Estimate Mendelian Sampling Effects and Selection Limits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Limits to selection and Mendelian sampling terms can be calculated using haplotypes, by summing the individual additive effects on each chromosome. Haplotypes were imputed for 43,382 single nucleotide polymorphisms (SNP) in 1,455 Brown Swiss, 40,351 Holstein, and 4,064 Jersey bulls and cows using th...

  15. First Report of Haplotype I-b of Phytophthora infestans in central Mexico

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Central Mexico is considered a center of genetic diversity for P. infestans based on a range of genotypic and phenotypic characteristics. Surprisingly, while mtDNA haplotypes I-a, II-a and II-b have been reported from central Mexico, haplotype I-b has not been found in central Mexico. Therefore a mo...

  16. Brazilian Angiostrongylus cantonensis haplotypes, ac8 and ac9, have two different biological and morphological profiles

    PubMed Central

    Monte, Tainá CC; Gentile, Rosana; Garcia, Juberlan; Mota, Ester; Santos, Jeannie N; Maldonado, Arnaldo

    2014-01-01

    Angiostrongylus cantonensis is the etiologic agent of eosinophilic meningoencephalitis in humans. Cases have been recorded in many parts of the world, including Brazil. The aim of this study was to compare the differences in the biology and morphology of two different Brazilian haplotypes of A. : ac8 and ac9. A significantly larger number of L1 larvae eliminated in the faeces of rodents at the beginning of the patent period was observed for ac9 haplotype and compared to the total of L1 larvae eliminated, there was a significant difference between the two haplotypes. The ac9 haplotype showed a significant difference in the proportion of female and male specimens (0.6:1), but the same was not observed for ac8 (1.2:1). The morphometric analysis showed that male and female specimens isolated from ac8 haplotype were significantly larger with respect to body length, oesophagus length, spicule length (male) and distance from the anus to the rear end (female) compared to specimens from ac9. The morphological analysis by light microscopy showed little variation in the level of bifurcations at the lateral rays in the right lobe of the copulatory bursa between the two haplotypes. The biological, morphological and morphometric variations observed between the two haplotypes agree with the observed variation at the molecular level using the cytochrome oxidase subunit I marker and reinforce the possible influence of geographical isolation on the development of these haplotypes. PMID:25591110

  17. Evolutionary relationship between human major histocompatibility complex HLA-DR haplotypes

    SciTech Connect

    Svensson, A.C.; Setterblad, N.; Pihlgren, U.; Rask, L.; Andersson, G.

    1996-09-01

    HLA-DR haplotypes of the human major histocompatibility complex are organized in five different groups. They can be identified based on the serological specificity expressed by the polymorphic DRB1 locus and by the presence of a characteristic set of DRB genes. The nucleotide sequences of introns 4 and 5 of the two DRB genes (DRB1*01 and DRB6*01) from a DR1 haplotype and the three DRB genes (DRB1*15, DRB6*15, and DRB5*15), from a DR51 haplotype were determined. This study identified endogenous retroviral long terminal repeat elements (ERV9 LTR) located at identical positions in intron 5 of the DRB1 genes in both the DR1 and DR51 haplotypes. Phylogenetic analyses revealed a close evolutionary relationship between these two haplotypes. The DRB5 gene, unique for the DR51 haplotype, may have been lost by a recent gene deletion event creating the DR1 haplotype. A model for the evolution of the human DR haplotypes involving separate duplication and contraction events is presented. 55 refs., 5 figs., 2 tabs.

  18. Clarifying haplotype ambiguity of NAT2 in multi-national cohorts.

    PubMed

    Selinski, Silvia; Blaszkewicz, Meinolf; Agundez, Jose A G; Martinez, Carmen; Garcia-Martin, Elena; Hengstler, Jan G; Golka, Klaus

    2013-01-01

    N-Acetyltransferase 2 (NAT2) is the key enzyme in aromatic amine metabolism. NAT2 genotyping requires a subsequent determination of the haplotype pairs (formerly: alleles) to derive the acetylation status. The chromosomal phase of the single nucleotide polymorphisms (SNPs) is unclear for about 2/3 of the genotypes. We investigated NAT2 genotypes of 1,234 bladder cancer cases and 2,207 controls from Germany, Hungary, Pakistan and Venezuela plus 696 further German cancer cases. We reconstructed NAT2 haplotypes using PHASE v2.1.1. We analysed if the variability of the NAT2 haplotypes affected the haplotype reconstruction. Furthermore, we compared population haplotype frequencies in three Caucasian control cohorts (German, Hungarian, Spanish), in Pakistanis and Venezuelans and the impact on bladder cancer. We conclude that a common haplotype reconstruction is feasible, enhances precision and reliability. Hungarian controls showed the largest intra-ethnic variability whereas the Pakistanis showed a haplotype distribution typical for Caucasians. The main differences could be observed for the slow haplotypes *5B, *6A and *7B. The association of slow NAT2 genotypes with bladder cancer risk was most prominent in the Venezuelan study group. PMID:23277078

  19. Frequency-based haplotype reconstruction from deep sequencing data of bacterial populations

    PubMed Central

    Pulido-Tamayo, Sergio; Sánchez-Rodríguez, Aminael; Swings, Toon; Van den Bergh, Bram; Dubey, Akanksha; Steenackers, Hans; Michiels, Jan; Fostier, Jan; Marchal, Kathleen

    2015-01-01

    Clonal populations accumulate mutations over time, resulting in different haplotypes. Deep sequencing of such a population in principle provides information to reconstruct these haplotypes and the frequency at which the haplotypes occur. However, this reconstruction is technically not trivial, especially not in clonal systems with a relatively low mutation frequency. The low number of segregating sites in those systems adds ambiguity to the haplotype phasing and thus obviates the reconstruction of genome-wide haplotypes based on sequence overlap information. Therefore, we present EVORhA, a haplotype reconstruction method that complements phasing information in the non-empty read overlap with the frequency estimations of inferred local haplotypes. As was shown with simulated data, as soon as read lengths and/or mutation rates become restrictive for state-of-the-art methods, the use of this additional frequency information allows EVORhA to still reliably reconstruct genome-wide haplotypes. On real data, we show the applicability of the method in reconstructing the population composition of evolved bacterial populations and in decomposing mixed bacterial infections from clinical samples. PMID:25990729

  20. The influence of interleukin 7 receptor α chain haplotypes on outcome after allogeneic hematopoietic cell transplantation

    PubMed Central

    Broux, Bieke; Shamim, Zaiba; Wang, Tao; Spellman, Stephen; Haagenson, Michael; Stinissen, Piet; Ryder, Lars Peter; Müller, Klaus; Hellings, Niels

    2014-01-01

    Summary We investigated the influence of IL-7 receptor α chain (IL-7Rα) gene haplotypes in donors on the outcome of haematopoietic cell transplantation (HCT). Unlike the association between single donor SNPs and HCT outcome found previously, only trends towards association were found here, due to “dilution” of SNPs into haplotypes. PMID:25352021

  1. Distribution of beta-globin haplotypes among the tribes of southern Gujarat, India.

    PubMed

    Aggarwal, Aastha; Khurana, Priyanka; Mitra, Siuli; Raicha, Bhavesh; Saraswathy, K N; Italia, Yazdi M; Kshatriya, Gautam K

    2013-06-01

    The present study was carried out in Indo-European speaking tribal population groups of southern Gujarat (India) to elucidate the allelic and haplotypic content of β-globin system in individuals with HbAA genotypes. 6 neutral restriction sites of the β-globin system were analysed and various statistical parameters were estimated to draw meaningful interpretations. All the 6 sites were found to be polymorphic and most were in Hardy-Weinberg Equilibrium in the studied group. Haplotypes were constructed using two different combinations of the 6 restriction sites analysed. Analysis of the 5 sites revealed a set of three predominant haplotypes, '+----', '-++-+' and '-+-++'; and haplotypes '+--', '++-' and '+++' were found to be the most frequent when the 3 sites were used to construct the haplotypes. Haplotypic heterozygosity levels (>83%) observed in the present study group were comparable to those observed in African and Afro-American populations and greater than other world populations. All the ancestral haplotypes, +-----, -++-+, -+-++ and ----+ were found in the study group. The distribution pattern of various haplotypes was consistent with the global pattern. The paucity of comparable data from other Indian populations restricted one from making interpretations about the study group's relationships with other Indian populations but the results were indicative of older population histories or experience of gene flow by the study group and their affinities with populations of southern India. PMID:23500448

  2. Improving burial practices and cemetery management during an Ebola virus disease epidemic - Sierra Leone, 2014.

    PubMed

    Nielsen, Carrie F; Kidd, Sarah; Sillah, Ansumana R M; Davis, Edward; Mermin, Jonathan; Kilmarx, Peter H

    2015-01-16

    As of January 3, 2015, Ebola virus disease (Ebola) has killed more than 2,500 persons in Sierra Leone since the epidemic began there in May 2014. Ebola virus is transmitted principally by direct physical contact with an infected person or their body fluids during the later stages of illness or after death. Contact with the bodies and fluids of persons who have died of Ebola is especially common in West Africa, where family and community members often touch and wash the body of the deceased in preparation for funerals. These cultural practices have been a route of Ebola transmission. In September 2014, CDC, in collaboration with the Sierra Leone Ministry of Health and Sanitation (MOH), assessed burial practices, cemetery management, and adherence to practices recommended to reduce the risk for Ebola virus transmission. The assessment was conducted by directly observing burials and cemetery operations in three high-incidence districts. In addition, a community assessment was conducted to assess the acceptability to the population of safe, nontraditional burial practices and cemetery management intended to reduce the risk for Ebola virus transmission. This report summarizes the results of these assessments, which found that 1) there were not enough burial teams to manage the number of reported deaths, 2) Ebola surveillance, swab collection, and burial team responses to a dead body alert were not coordinated, 3) systematic procedures for testing and reporting of Ebola laboratory results for dead bodies were lacking, 4) cemetery space and management were inadequate, and 5) safe burial practices, as initially implemented, were not well accepted by communities. These findings were used to inform the development of a national standard operating procedure (SOP) for safe, dignified medical burials, released on October 1. A second, national-level, assessment was conducted during October 10-15 to assess burial team practices and training and resource needs for SOP

  3. Y chromosome probe p49a detects complex PvuII haplotypes and many new TaqI haplotypes in southern African populations.

    PubMed Central

    Spurdle, A; Jenkins, T

    1992-01-01

    Y-specific 49a/TaqI haplotypes were determined for 831 individuals drawn from 21 different southern African populations. A total of 31 new haplotypes were observed, some of which contained new alleles or allelic variants. Duplication, in addition to CpG mutation, is implicated in the generation of certain allelic variants. Cluster analysis of genetic distances between the populations, calculated using the 49a/TaqI haplotype frequencies, revealed a basic split between African and non-African populations. Hybrid groups cluster with the caucasoid groups, indicating that male gene flow has occurred from the latter into the former. Clustering of the negroid and Khoisan groups is not what might have been expected from the known linguistic affinities. It is suggested that the 49a/TaqI haplotype analysis of these populations is not sufficiently sensitive to distinguish between many of the populations. The Y-specific 49a/PvuII polymorphism was studied in 127 individuals from southern African populations, and 17 polymorphic fragments ranging in size from 3.6 kb to greater than 48 kb were identified. A total of 53 PvuII haplotypes were observed, corresponding to only 30 TaqI haplotypes. There appears to be poor correlation between the two polymorphisms. Images Figure 2 Figure 4 PMID:1729883

  4. Musical aptitude is associated with AVPR1A-haplotypes.

    PubMed

    Ukkola, Liisa T; Onkamo, Päivi; Raijas, Pirre; Karma, Kai; Järvelä, Irma

    2009-01-01

    Artistic creativity forms the basis of music culture and music industry. Composing, improvising and arranging music are complex creative functions of the human brain, which biological value remains unknown. We hypothesized that practicing music is social communication that needs musical aptitude and even creativity in music. In order to understand the neurobiological basis of music in human evolution and communication we analyzed polymorphisms of the arginine vasopressin receptor 1A (AVPR1A), serotonin transporter (SLC6A4), catecol-O-methyltranferase (COMT), dopamin receptor D2 (DRD2) and tyrosine hydroxylase 1 (TPH1), genes associated with social bonding and cognitive functions in 19 Finnish families (n = 343 members) with professional musicians and/or active amateurs. All family members were tested for musical aptitude using the auditory structuring ability test (Karma Music test; KMT) and Carl Seashores tests for pitch (SP) and for time (ST). Data on creativity in music (composing, improvising and/or arranging music) was surveyed using a web-based questionnaire. Here we show for the first time that creative functions in music have a strong genetic component (h(2) = .84; composing h(2) = .40; arranging h(2) = .46; improvising h(2) = .62) in Finnish multigenerational families. We also show that high music test scores are significantly associated with creative functions in music (p<.0001). We discovered an overall haplotype association with AVPR1A gene (markers RS1 and RS3) and KMT (p = 0.0008; corrected p = 0.00002), SP (p = 0.0261; corrected p = 0.0072) and combined music test scores (COMB) (p = 0.0056; corrected p = 0.0006). AVPR1A haplotype AVR+RS1 further suggested a positive association with ST (p = 0.0038; corrected p = 0.00184) and COMB (p = 0.0083; corrected p = 0.0040) using haplotype-based association test HBAT. The results suggest that the neurobiology of music perception and production is likely to be related to the pathways affecting intrinsic

  5. Musical Aptitude Is Associated with AVPR1A-Haplotypes

    PubMed Central

    Ukkola, Liisa T.; Onkamo, Päivi; Raijas, Pirre; Karma, Kai; Järvelä, Irma

    2009-01-01

    Artistic creativity forms the basis of music culture and music industry. Composing, improvising and arranging music are complex creative functions of the human brain, which biological value remains unknown. We hypothesized that practicing music is social communication that needs musical aptitude and even creativity in music. In order to understand the neurobiological basis of music in human evolution and communication we analyzed polymorphisms of the arginine vasopressin receptor 1A (AVPR1A), serotonin transporter (SLC6A4), catecol-O-methyltranferase (COMT), dopamin receptor D2 (DRD2) and tyrosine hydroxylase 1 (TPH1), genes associated with social bonding and cognitive functions in 19 Finnish families (n = 343 members) with professional musicians and/or active amateurs. All family members were tested for musical aptitude using the auditory structuring ability test (Karma Music test; KMT) and Carl Seashores tests for pitch (SP) and for time (ST). Data on creativity in music (composing, improvising and/or arranging music) was surveyed using a web-based questionnaire. Here we show for the first time that creative functions in music have a strong genetic component (h2 = .84; composing h2 = .40; arranging h2 = .46; improvising h2 = .62) in Finnish multigenerational families. We also show that high music test scores are significantly associated with creative functions in music (p<.0001). We discovered an overall haplotype association with AVPR1A gene (markers RS1 and RS3) and KMT (p = 0.0008; corrected p = 0.00002), SP (p = 0.0261; corrected p = 0.0072) and combined music test scores (COMB) (p = 0.0056; corrected p = 0.0006). AVPR1A haplotype AVR+RS1 further suggested a positive association with ST (p = 0.0038; corrected p = 0.00184) and COMB (p = 0.0083; corrected p = 0.0040) using haplotype-based association test HBAT. The results suggest that the neurobiology of music perception and production is likely to be

  6. Melatonin membrane receptor (MT1R) expression and nitro-oxidative stress in testis of golden hamster, Mesocricetus auratus: An age-dependent study.

    PubMed

    Mukherjee, Arun; Haldar, Chandana

    2015-09-01

    Age-dependent decline in melatonin level induces nitro-oxidative stress that compromises physiological homeostasis including reproduction. However, less information exist regarding the age-dependent variation in local melatonin (lMel) concentration and MT1R expression in testis and its interaction with testicular steroidogenesis and nitro-oxidative stress in golden hamster, Mesocricetus auratus. Therefore, we evaluated lMel level along with MT1R expression and its possible interaction with steroidogenesis and nitro-oxidative stress in testes of young (6weeks), adult (15weeks) and old (2years) aged hamsters. Further, we injected the old hamsters with melatonin to address whether age-related decline in lMel and MT1R is responsible for the reduction in testicular steroidogenesis and antioxidant status. Increased expression of steroidogenic markers suggests increased testicular steroidogenesis in adult hamsters that declined in old hamsters. An age-dependent elevation in the level of NOX, TBARS, corticosterone and the expression of iNOS and GR with a concomitant decrease in enzyme activities for SOD, CAT, GSH-PX indicate increased nitro-oxidative stress in testes. Data suggest that reproductive senescence in male hamsters might be a consequence of declined lMel concentration with MT1R expression inducing nitro-oxidative stress resulting in diminished testicular steroidogenesis. However, administration of Mel in old-aged hamsters significantly increased steroidogenesis and antioxidant status without a significant variation in lMel concentration and MT1R expression in testes. Therefore, decreased lMel and MT1R might not be the causative factor underlying the age-associated decrease in antioxidant defence and steroidogenesis in testes. In conclusion, Mel induced amelioration of testicular oxidative insult and elevation of steroidogenic activity suggests a potential role of increased nitro-oxidative stress underlying the age-dependent decrease in steroidogenesis. PMID

  7. A haplotypic approach to founder-origin probabilities and outbred QTL analysis.

    PubMed

    Reyes-Valdès, M Humberto; Williams, Claire G

    2002-12-01

    Founder-origin probability methods are used to trace specific chromosomal segments in individual offspring. A haplotypic method was developed for calculating founder-origin probabilities in three-generation outbred pedigrees suited to quantitative trait locus (QTL) analysis. Estimators for expected founder-origin proportions were derived for a linkage group segment, an entire linkage group and a complete haplotype. If the founders are truly outbred, the haplotypic method gives a close approximation when compared with the Haley et al. (1994) method that simultaneously uses all marker information for QTL analysis, and it is less computationally demanding. The chief limitation of the haplotypic method is that some information in two-allele intercross marker-type configurations is ignored. Informativeness of marker arrays is discussed in the framework of founder-origin probabilities and proportions. The haplotypic method can be extended to more complex pedigrees with additional generations. PMID:12688662

  8. Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel.

    PubMed

    Delaneau, Olivier; Marchini, Jonathan

    2014-01-01

    A major use of the 1000 Genomes Project (1000 GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000 GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. PMID:25653097

  9. Accurate whole genome sequencing and haplotyping from10-20 human cells

    PubMed Central

    Peters, Brock A.; Kermani, Bahram G.; Sparks, Andrew B.; Alferov, Oleg; Hong, Peter; Alexeev, Andrei; Jiang, Yuan; Dahl, Fredrik; Tang, Y. Tom; Haas, Juergen; Robasky, Kimberly; Zaranek, Alexander Wait; Lee, Je-Hyuk; Ball, Madeleine Price; Peterson, Joseph E.; Perazich, Helena; Yeung, George; Liu, Jia; Chen, Linsu; Kennemer, Michael I.; Pothuraju, Kaliprasad; Konvicka, Karel; Tsoupko-Sitnikov, Mike; Pant, Krishna P.; Ebert, Jessica C.; Nilsen, Geoffrey B.; Baccash, Jonathan; Halpern, Aaron L.; Church, George M.; Drmanac, Radoje

    2012-01-01

    Recent advances in whole genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, Long Fragment Read (LFR) technology, similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ~100 pg of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants (SNVs) were assembled into long haplotype contigs. Removal of false positive SNVs not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10 Mb. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications. PMID:22785314

  10. Organelle DNA haplotypes reflect crop-use characteristics and geographic origins of Cannabis sativa.

    PubMed

    Gilmore, Simon; Peakall, Rod; Robertson, James

    2007-10-25

    Comparative sequencing of cannabis individuals across 12 chloroplast and mitochondrial DNA loci revealed 7 polymorphic sites, including 5 length variable regions and 2 single nucleotide polymorphisms. Simple PCR assays were developed to assay these polymorphisms, and organelle DNA haplotypes were obtained for 188 cannabis individuals from 76 separate populations, including drug-type, fibre-type and wild populations. The haplotype data were analysed using parsimony, UPGMA and neighbour joining methods. Three haplotype groups were recovered by each analysis method, and these groups are suggestive of the crop-use characteristics and geographical origin of the populations, although not strictly diagnostic. We discuss the relationship between our haplotype data and taxonomic opinions of cannabis, and the implications of organelle DNA haplotyping to forensic investigations of cannabis. PMID:17293071

  11. Vaccination against rubella: Analysis of the temporal evolution of the age-dependent force of infection and the effects of different contact patterns

    NASA Astrophysics Data System (ADS)

    Amaku, M.; Coutinho, F. A.; Azevedo, R. S.; Burattini, M. N.; Lopez, L. F.; Massad, E.

    2003-05-01

    In this paper, we analyze the temporal evolution of the age-dependent force of infection and incidence of rubella, after the introduction of a very specific vaccination program in a previously nonvaccinated population where rubella was in endemic steady state. We deduce an integral equation for the age-dependent force of infection, which depends on a number of parameters that can be estimated from the force of infection in a steady state prior to the vaccination program. We present the results of our simulations, which are compared with observed data. We also examine the influence of contact patterns among members of a community on the age-dependent intensity of transmission of rubella and on the results of vaccination strategies. As an example of the theory proposed, we calculate the effects of vaccination strategies for four communities from Caieiras (Brazil), Huixquilucan (Mexico), Finland, and the United Kingdom. The results for each community differ considerably according to the distinct intensity and pattern of transmission in the absence of vaccination. We conclude that this simple vaccination program is not very efficient (very slow) in the goal of eradicating the disease. This gives support to a mixed strategy, proposed by Massad et al., accepted and implemented by the government of the State of São Paulo, Brazil.

  12. Dynein Dysfunction Reproduces Age-Dependent Retromer Deficiency: Concomitant Disruption of Retrograde Trafficking Is Required for Alteration in β-Amyloid Precursor Protein Metabolism.

    PubMed

    Kimura, Nobuyuki; Samura, Eriko; Suzuki, Keiko; Okabayashi, Sachi; Shimozawa, Nobuhiro; Yasutomi, Yasuhiro

    2016-07-01

    It is widely accepted that β-amyloid (Aβ) protein plays a pivotal role in Alzheimer disease pathogenesis, and accumulating evidence suggests that endocytic dysfunction is involved in Aβ pathology. Retromer, a conserved multisubunit complex, mediates the retrograde transport of numerous kinds of cargo from endosomes to the trans-Golgi network. Several studies have found that retromer deficiency enhances Aβ pathology both in vitro and in vivo. Cytoplasmic dynein, a microtubule-based motor protein, mediates minus-end-directed vesicle transport via interactions with dynactin, another microtubule-associated protein that also interacts with retromer. Aging attenuates the dynein-dynactin interaction, and dynein dysfunction reproduces age-dependent endocytic disturbance, resulting in the intracellular accumulation of beta-amyloid precursor protein (APP) and its β-cleavage products, including Aβ. Here, we report that aging itself affects retromer trafficking in cynomolgus monkey brains. In addition, dynein dysfunction reproduces this type of age-dependent retromer deficiency (ie, the endosomal accumulation of retromer-related proteins and APP. Moreover, we found that knockdown of Rab7, Rab9, or Rab11 did not alter endogenous APP metabolism, such as that observed in aged monkey brains and in dynein-depleted cells. These findings suggest that dynein dysfunction can cause retromer deficiency and that concomitant disruption of retrograde trafficking may be the key factor underlying age-dependent Aβ pathology. PMID:27179390

  13. Interleukin-10 Haplotype May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer

    PubMed Central

    Wu, Tzu-Chin; Wang, Lee; Chien, Wen-Pin; Cheng, Ya-Wen; Chen, Chih-Yi; Shieh, Shwn-Huey; Lee, Huei

    2012-01-01

    IL-10 is associated with tumor malignancy via immune escape. We hypothesized that IL-10 haplotypes categorized by IL-10 promoter polymorphisms at –1082A>G, –819C>T, and –592C>A might influence IL-10 expression and give rise to non-small cell lung cancer (NSCLC) patients with poor outcomes and relapse. We collected adjacent normal tissues from 385 NSCLC patients to determine IL-10 haplotypes by direct sequencing and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Of the 385 tumors, 241 were available to evaluate IL-10 mRNA expression levels by real-time RT-PCR. The influence of IL-10 haplotypes on overall survival (OS) and relapse free survival (RFS) were determined by Kaplan-Meier and multivariate Cox regression analysis. The results showed that IL-10 mRNA levels were significantly higher in tumors with the non-ATA haplotype than with the ATA haplotype (P = 0.004). Patients with the non-ATA haplotype had shorter OS and RFS periods than did patients with the ATA haplotype. This may be associated with the observation that the number of tumor-infiltrating lymphocytes was decreased in the tumors with higher levels of IL-10. Consistently, T cells from the peripheral blood of the patients with non-ATA haplotype were more susceptible to apoptosis and less cytotoxic to tumor cells, compared to those from the patients with ATA haplotype. The results suggest that IL-10 can promote tumor malignancy via promoting T cell apoptosis and tumor cell survival, and IL-10 haplotype evaluated by PCR-RFLP or direct sequencing may be used to predict survival and relapse in resected NSCLC, helping clinicians to make appropriate decisions on treatment of the patients. PMID:22848356

  14. Association of Nrf2 Polymorphism Haplotypes with Acute Lung Injury Phenotypes in Inbred Strains of Mice

    PubMed Central

    Jedlicka, Anne E.; Gladwell, Wesley; Marzec, Jacqui; McCaw, Zackary R.; Bienstock, Rachelle J.; Kleeberger, Steven R.

    2015-01-01

    Abstract Aims: Nrf2 is a master transcription factor for antioxidant response element (ARE)-mediated cytoprotective gene induction. A protective role for pulmonary Nrf2 was determined in model oxidative disorders, including hyperoxia-induced acute lung injury (ALI). To obtain additional insights into the function and genetic regulation of Nrf2, we assessed functional single nucleotide polymorphisms (SNPs) of Nrf2 in inbred mouse strains and tested whether sequence variation is associated with hyperoxia susceptibility. Results: Nrf2 SNPs were compiled from publicly available databases and by re-sequencing DNA from inbred strains. Hierarchical clustering of Nrf2 SNPs categorized the strains into three major haplotypes. Hyperoxia susceptibility was greater in haplotypes 2 and 3 strains than in haplotype 1 strains. A promoter SNP −103 T/C adding an Sp1 binding site in haplotype 2 diminished promoter activation basally and under hyperoxia. Haplotype 3 mice bearing nonsynonymous coding SNPs located in (1862 A/T, His543Gln) and adjacent to (1417 T/C, Thr395Ile) the Neh1 domain showed suppressed nuclear transactivation of pulmonary Nrf2 relative to other strains, and overexpression of haplotype 3 Nrf2 showed lower ARE responsiveness than overexpression of haplotype 1 Nrf2 in airway cells. Importantly, we found a significant correlation of Nrf2 haplotypes and hyperoxic lung injury phenotypes. Innovation and Conclusion: The results indicate significant influence of Nrf2 polymorphisms and haplotypes on gene function and hyperoxia susceptibility. Our findings further support Nrf2 as a genetic determinant in ALI pathogenesis and provide useful tools for investigators who use mouse strains classified by Nrf2 haplotypes to elucidate the role for Nrf2 in oxidative disorders. Antioxid. Redox Signal. 22, 325–338. PMID:25268541

  15. Towards Making a LEON3 Multicore Compatible with Probabilistic Timing Analysis

    NASA Astrophysics Data System (ADS)

    Hernandez, Carles; Abella, Jaume; Cazorla, Francisco J.; Andersson, Jan; Gianarro, Andrea

    2015-09-01

    Timing analysis must be performed for safetycritical real-time tasks to estimate their Worst-Case Execution Time (WCET). The advent of multicores and cache hierarchies challenges the use of traditional measurement-based timing analysis (MBTA), which is current practice in industry. To tackle this issue a new family of timing analysis techniques based on probabilistic analysis has recently arised. Among those, Measurement-Based Probabilistic Timing Analysis (MBPTA) is the most promising approach, but imposes some constraints on the hardware design. In this paper we analyze the case of a LEON3 multicore processor, identify those features that need to be modified to attain MBPTA compliance and show the first steps towards achieving it. Our preliminary results show that (i) low WCET estimates can be derived, (ii) industrial practice based on measurements can be kept, and (iii) average performance is only slightly harmed w.r.t. non-MBPTA-compliant hardware designs.

  16. Generalized symmetries of an 𝓝 = 1 supersymmetric Boiti-Leon-Manna-Pempinelli system

    NASA Astrophysics Data System (ADS)

    Wang, Jian-Yong; Tang, Xiao-Yan; Liang, Zu-Feng; Lou, Sen-Yue

    2015-05-01

    The formal series symmetry approach (FSSA), a quite powerful and straightforward method to establish infinitely many generalized symmetries of classical integrable systems, has been successfully extended in the supersymmetric framework to explore series of infinitely many generalized symmetries for supersymmetric systems. Taking the 𝒩 = 1 supersymmetric Boiti-Leon-Manna-Pempinelli system as a concrete example, it is shown that the application of the extended FSSA to this supersymmetric system leads to a set of infinitely many generalized symmetries with an arbitrary function f (t). Some interesting special cases of symmetry algebras are presented, including a limit case f (t) = 1 related to the commutativity of higher order generalized symmetries. Project supported by the National Natural Science Foundation of China (Grant Nos. 11275123, 11175092, 11475052, and 11435005), the Shanghai Knowledge Service Platform for Trustworthy Internet of Things, China (Grant No. ZF1213), and the Talent Fund and K CWong Magna Fund in Ningbo University, China.

  17. Cosmogenic helium and volatile-rich fluid in Sierra Leone alluvial diamonds

    NASA Technical Reports Server (NTRS)

    Mcconville, P.; Reynolds, J. H.

    1989-01-01

    Noble gas measurements were carried out on two identical splits of a finely powdered harshly acid-washed sample derived from fragments of a single alluvial diamond from Sierra Leone, with essentially identical results obtained for both splits. Isotopic ratios for Ar, Kr, and Xe were found to be atmospheric. Their elemental abundances were high relative to published data, owing to the effect of shock implantation in the crushing step, as was verified in a supplementary experiment. No Ne was detected above the blank level. The He-3 was exceptionally abundant, while He-4 was exceptionally depleted, possibly due to the acid wash. The He-3/He-4 ratio was anomalously high at an R/Ra value of 246 + or - 16. The results support the hypothesis that the He-3 excess in diamonds is cosmogenic.

  18. Gender differences in support for the discontinuation of female genital cutting in Sierra Leone.

    PubMed

    Sagna, Marguerite L

    2014-06-01

    Despite decades of policies, interventions and legislation, many girls and women are being subjected to female genital cutting (FGC) across the African continent. Because FGC has profound implications for women's wellbeing and reproductive health rights, an examination of behavioural changes toward the practice is imperative to reinforce strategies directed at eradicating it. Using a nationally representative survey, this study examines support for discontinuation of FGC and its associated predictors among both women and men in Sierra Leone. Findings reveal gender differences in attitudes toward the elimination of the practice across most of the socioeconomic predictors. Interestingly, beliefs about and perceived benefits of FGC emerge as important determinants of the support for the elimination of FGC, both genders considered. The findings highlight the importance of achieving gender equality and women's empowerment, and the necessity for a more contextualised approach to FGC eradication. PMID:24735172

  19. Prevalence of Autism Spectrum Disorders in Guanajuato, Mexico: The Leon survey.

    PubMed

    Fombonne, Eric; Marcin, Carlos; Manero, Ana Cecilia; Bruno, Ruth; Diaz, Christian; Villalobos, Michele; Ramsay, Katrina; Nealy, Benjamin

    2016-05-01

    There are no epidemiological data on autism for Mexico. This study was conducted to generate a first estimate of ASD prevalence in Mexico. We surveyed children age eight in Leon (Guanajuato). The sample was stratified in two strata: (1) children having special education and medical records (SEMR; N = 432) and (2) children attending regular schools (GSS; N = 11,684). GSS children were screened with the SRS and those with the highest scores were invited to a diagnostic evaluation. The final sample comprised 36 children (80.6 % male) who had confirmed ASD. A third had intellectual disability, 25 % were non-verbal, 69 % had co-occurring behavioral problems. The prevalence overall was 0.87 % (95 % CI 0.62, 1.1 %). This survey provides an estimate for ASD prevalence in Mexico that is consistent with recent studies. PMID:26797939

  20. Sierra Leone's Former Child Soldiers: A Follow-up Study of Psychosocial Adjustment and Community Reintegration

    PubMed Central

    Betancourt, Theresa Stichick; Borisova, Ivelina Ivanova; Williams, Timothy Philip; Brennan, Robert T.; Whitfield, T. Hatch; de la Soudiere, Marie; Williamson, John; Gilman, Stephen E.

    2009-01-01

    This is the first prospective study to investigate psychosocial adjustment in male and female former child soldiers (n=156, 12% female). The study began in Sierra Leone in 2002 and was designed to examine both risk and protective factors in psychosocial adjustment. Over the two-year period of follow up, youth who had wounded or killed others during the war demonstrated increases in hostility. Youth who survived rape had higher levels of anxiety and hostility, but also demonstrated greater confidence and prosocial attitudes at follow up. Of the potential protective resources examined, improved community acceptance was associated with reduced depression at follow up and improved confidence and prosocial attitudes regardless of levels of violence exposure. Retention in school was also associated with greater prosocial attitudes. PMID:20636683

  1. Stratified Sampling of Neighborhood Sections for Population Estimation: A Case Study of Bo City, Sierra Leone

    PubMed Central

    Hillson, Roger; Alejandre, Joel D.; Jacobsen, Kathryn H.; Ansumana, Rashid; Bockarie, Alfred S.; Bangura, Umaru; Lamin, Joseph M.; Stenger, David A.

    2015-01-01

    There is a need for better estimators of population size in places that have undergone rapid growth and where collection of census data is difficult. We explored simulated estimates of urban population based on survey data from Bo, Sierra Leone, using two approaches: (1) stratified sampling from across 20 neighborhoods and (2) stratified single-stage cluster sampling of only four randomly-sampled neighborhoods. The stratification variables evaluated were (a) occupants per individual residence, (b) occupants per neighborhood, and (c) residential structures per neighborhood. For method (1), stratification variable (a) yielded the most accurate re-estimate of the current total population. Stratification variable (c), which can be estimated from aerial photography and zoning type verification, and variable (b), which could be ascertained by surveying a limited number of households, increased the accuracy of method (2). Small household-level surveys with appropriate sampling methods can yield reasonably accurate estimations of urban populations. PMID:26177479

  2. Stratified Sampling of Neighborhood Sections for Population Estimation: A Case Study of Bo City, Sierra Leone.

    PubMed

    Hillson, Roger; Alejandre, Joel D; Jacobsen, Kathryn H; Ansumana, Rashid; Bockarie, Alfred S; Bangura, Umaru; Lamin, Joseph M; Stenger, David A

    2015-01-01

    There is a need for better estimators of population size in places that have undergone rapid growth and where collection of census data is difficult. We explored simulated estimates of urban population based on survey data from Bo, Sierra Leone, using two approaches: (1) stratified sampling from across 20 neighborhoods and (2) stratified single-stage cluster sampling of only four randomly-sampled neighborhoods. The stratification variables evaluated were (a) occupants per individual residence, (b) occupants per neighborhood, and (c) residential structures per neighborhood. For method (1), stratification variable (a) yielded the most accurate re-estimate of the current total population. Stratification variable (c), which can be estimated from aerial photography and zoning type verification, and variable (b), which could be ascertained by surveying a limited number of households, increased the accuracy of method (2). Small household-level surveys with appropriate sampling methods can yield reasonably accurate estimations of urban populations. PMID:26177479

  3. Strategic environmental assessment of hydrological and irrigation plans in Castilla y Leon, Spain

    SciTech Connect

    Hedo, D.; Bina, O. )

    1999-05-01

    The study illustrates how strategic environmental assessment (SEA) can promote sustainable development plans. It defines and applies an SEA methodology to two draft plans: the hydrological plan for the Duero basin in Spain and the irrigation plan for the region of Castilla y Leon. Although prepared by national and regional authorities, respectively, both draft plans refer to the management and use of water as a resource for economic development and refer roughly to the same area. The SEA addresses the environmental, economic, and social impacts of the combined draft plans, using relevant indicators and objectives. The analysis shows that the proposals would lead to high financial costs and significant negative impacts on the environment for each job created; it develops and assesses a number of alternatives that would address these impacts. The results are used to define SEA procedures for the new Structural Funds period (2000--2006) and will provide a useful lesson for plans at all levels of government within Spain.

  4. Cosmogenic helium and volatile-rich fluid in Sierra leone alluvial diamonds

    SciTech Connect

    McConville, P.; Reynolds, J.H. )

    1989-09-01

    Pursuant to the discovery elsewhere of cosmogenic {sup 10}Be in alluvial diamond fragments from Zaire, noble gas measurements were made on two identical splits of a finely powdered, harshly acid-washed sample derived from selected (for clarity) fragments of a single alluvial diamond from Sierra Leone (sample LJA {yields} L4 and L5). Essentially identical results were obtained for both splits. Isotopic ratios for Ar, Kr, and Xe were atmospheric and their elemental abundances were high relative to published data, owing to shock implantation in the crushing as verified in a supplementary experiment. No neon was detected above blank level. {sup 3}He was exceptionally abundant, {sup 4}He exceptionally depleted, possibly from the acid wash, and the ratio {sup 3}He/{sup 4}He almost unprecedentedly high at an R/R{sub a} value of 246 {plus minus} 16. The results support the hypothesis that excess {sup 3}He in diamonds is cosmogenic, although a cosmic-ray exposure of 5, 35, or (impossibly) 152 Ma for cyclic gardening of the sample to a maximum depth of 0, 4.6 m, or 20 m, respectively, is required. Troublesome for the cosmogenic hypothesis is a sample from very deep in the Finsch mine, South Africa, found by Zadnik et al (1987) to have an R/R{sub a} value of 1,000. This paper includes histograms of noble gas data published prior to mid-1988 for diamonds of known provenance. The Sierra Leone diamond studied in the supplementary experiment belongs to a distinct population of {sup 40*}Ar-rich diamonds consisting mostly of cubic diamonds for Zaire.

  5. Context matters: Community characteristics and mental health among war-affected youth in Sierra Leone

    PubMed Central

    Betancourt, Theresa S.; McBain, Ryan; Newnham, Elizabeth A.; Brennan, Robert T.

    2013-01-01

    Background Worldwide, over one billion children and adolescents live in war-affected settings. At present, only limited research has investigated linkages between disrupted social ecology and adverse mental health outcomes among war-affected youth. In this study, we examine three community-level characteristics—social disorder and collective efficacy within the community, as reported by caregivers, and perceived stigma as reported by youth—in relation to externalizing behaviors and internalizing symptoms among male and female former child soldiers in post-conflict Sierra Leone. Methods 243 former child soldiers (30% female, mean age at baseline: 16.6 years) and their primary caregivers participated in interviews in 2004 and 2008, as part of a larger prospective cohort study of war-affected youth in Sierra Leone. Two-point growth models were estimated to examine the relationship between community-level characteristics and externalizing and internalizing outcomes across the time points. Results Both social disorder within the community, reported by caregivers, and perceived stigma, reported by youth, positively co-varied with youths’ externalizing and internalizing scores—indicating that higher levels of each at baseline and follow-up were associated with higher levels of mental health problems at both time points (p<0.05). The relationship between collective efficacy and mental health outcomes was non-significant (p>0.05). Conclusions This study offers a rare glimpse into the role that the post-conflict social context plays in shaping mental health among former child soldiers. Results indicate that both social disorder and perceived stigma within the community demonstrate an important relationship to externalizing and internalizing problems among adolescent ex-combatants. Moreover, these relationships persisted over a four-year period of follow up. These results underscore the importance of the post-conflict social environment and the need to develop post

  6. Ebola Virus Disease Complications as Experienced by Survivors in Sierra Leone

    PubMed Central

    Tiffany, Amanda; Vetter, Pauline; Mattia, John; Dayer, Julie-Anne; Bartsch, Maria; Kasztura, Miriam; Sterk, Esther; Tijerino, Ana Maria; Kaiser, Laurent; Ciglenecki, Iza

    2016-01-01

    Background. Thousands of people have survived Ebola virus disease (EVD) during the ongoing outbreak. However, data about the frequency and risk factors of long-term post-EVD complications remain scarce. We describe the clinical characteristics of EVD survivors followed in a survivor clinic in Freetown, Sierra Leone. Methods. A survivor clinic opened within an Ebola treatment center compound in Freetown, Sierra Leone. At each visit, clinical and psychological assessments were conducted and free treatment was offered. Survivors were referred to a partner's hospitals if their condition could not be managed in the clinic. We used routinely collected data from the clinic to describe long-term complications of EVD and their risk factors. Results. A total of 1001 medical consultations for 166 patients were performed between 3 February and 21 June 2015. The most frequent complaints and diagnoses were arthralgia (n = 129 [77.7%]), fatigue (n = 116 [69.8%]), abdominal pain (n = 90 [54.2%]), headache (n = 87 [52.4%]), anemia (n = 83 [50%]), skin disorders (n = 81 [48.8%]), back pain (n = 54 [32.5%]), and alopecia (n = 53 [31.9%]). Ocular complications were diagnosed in 94 survivors (56.7%); uveitis was the most common (n = 57 [34%]). Survivors were 10 times more likely to develop uveitis post-EVD if they presented with red/injected eyes during the acute phase of their illness. Conclusions. Post-EVD complications among our patients were similar to those described previously and were detected early following the acute phase of disease. Follow-up of survivors should begin immediately after discharge to address sequelae as they arise and reduce the potential for development of long-term disabilities such as blindness. PMID:27001797

  7. Three Potato Centromeres Are Associated with Distinct Haplotypes with or Without Megabase-Sized Satellite Repeat Arrays

    PubMed Central

    Wang, Linsheng; Zeng, Zixian; Zhang, Wenli; Jiang, Jiming

    2014-01-01

    We report discoveries of different haplotypes associated with the centromeres of three potato chromosomes, including haplotypes composed of long arrays of satellite repeats and haplotypes lacking the same repeats. These results are in favor of the hypothesis that satellite repeat-based centromeres may originate from neocentromeres that lack repeats. PMID:24318533

  8. ACC interleukin-10 gene promoter haplotype as a breast cancer risk factor predictor among Jordanian females

    PubMed Central

    Atoum, Manar Fayiz

    2016-01-01

    Introduction Interleukin-10 (IL-10) is a multifactorial cytokine with a complex biological role in breast cancer. The aims of this study were to investigate any association between IL-10 gene promoter polymorphisms, 1082A>/G, −819T>C, and −592A>C, or haplotypes and breast cancer risk among Jordanian women and to evaluate any association between the most common haplotype with clinicopathological features of breast cancer. Patients and methods A total of 202 breast cancer patients and 210 age-matched healthy control subjects were genotyped for −1082A/G, −819T/C, and −592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reaction-restriction fragment length polymorphism. Study patients and control subjects were recruited from Prince Hamzah Hospital, Amman, Jordan (2012–2013). Ethical approval and signed consent forms were signed by all participants. DNA was extracted, and polymerase chain reaction fragments were amplified and restriction digested by MnII, MaeIII, and RsaI. Results This study showed no statistically significant difference between −1082A/G, −819T/C, and −592A/C IL-10 genotypes or alleles among breast cancer patients or controls. Four different haplotypes ATA, ACC, GTA, and ACA within the IL-10 promoter gene were determined among both breast cancer and control groups. The most frequent haplotype was ACC among breast cancer patients and controls (41.6% and 40.7%, respectively). No statistical differences in these haplotypes among breast cancer patients or controls were determined. Analysis of the most common ACC haplotype showed statistical difference in positive estrogen receptor (P=0.022), positive progesterone receptor (P=0.004), cancer grade (P=0.0001), and cancer stage (P=0.009) among the ACC haplotype compared to non-ACC haplotype. Conclusion To our knowledge, this is the first report studying the association of IL-10 haplotype with breast cancer risk events among Jordanian females. The

  9. Diversity of Extended HLA-DRB1 Haplotypes in the Finnish Population

    PubMed Central

    Wennerström, Annika; Vlachopoulou, Efthymia; Lahtela, L. Elisa; Paakkanen, Riitta; Eronen, Katja T.; Seppänen, Mikko; Lokki, Marja-Liisa

    2013-01-01

    The Major Histocompatibility Complex (MHC, 6p21) codes for traditional HLA and other host response related genes. The polymorphic HLA-DRB1 gene in MHC Class II has been associated with several complex diseases. In this study we focus on MHC haplotype structures in the Finnish population. We explore the variability of extended HLA-DRB1 haplotypes in relation to the other traditional HLA genes and a selected group of MHC class III genes. A total of 150 healthy Finnish individuals were included in the study. Subjects were genotyped for HLA alleles (HLA-A, -B, -DRB1, -DQB1, and -DPB1). The polymorphism of TNF, LTA, C4, BTNL2 and HLA-DRA genes was studied with 74 SNPs (single nucleotide polymorphism). The C4A and C4B gene copy numbers and a 2-bp silencing insertion at exon 29 in C4A gene were analysed with quantitative genomic realtime-PCR. The allele frequencies for each locus were calculated and haplotypes were constructed using both the traditional HLA alleles and SNP blocks. The most frequent Finnish A∼B∼DR -haplotype, uncommon in elsewhere in Europe, was A*03∼B*35∼DRB1*01∶01. The second most common haplotype was a common European ancestral haplotype AH 8.1 (A*01∼B*08∼DRB1*03∶01). Extended haplotypes containing HLA-B, TNF block, C4 and HLA-DPB1 strongly increased the number of HLA-DRB1 haplotypes showing variability in the extended HLA-DRB1 haplotype structures. On the contrary, BTNL2 block and HLA-DQB1 were more conserved showing linkage with the HLA-DRB1 alleles. We show that the use of HLA-DRB1 haplotypes rather than single HLA-DRB1 alleles is advantageous when studying the polymorphisms and LD patters of the MHC region. For disease association studies the HLA-DRB1 haplotypes with various MHC markers allows us to cluster haplotypes with functionally important gene variants such as C4 deficiency and cytokines TNF and LTA, and provides hypotheses for further assessment. Our study corroborates the importance of studying population-specific MHC

  10. Diversity of extended HLA-DRB1 haplotypes in the Finnish population.

    PubMed

    Wennerström, Annika; Vlachopoulou, Efthymia; Lahtela, L Elisa; Paakkanen, Riitta; Eronen, Katja T; Seppänen, Mikko; Lokki, Marja-Liisa

    2013-01-01

    The Major Histocompatibility Complex (MHC, 6p21) codes for traditional HLA and other host response related genes. The polymorphic HLA-DRB1 gene in MHC Class II has been associated with several complex diseases. In this study we focus on MHC haplotype structures in the Finnish population. We explore the variability of extended HLA-DRB1 haplotypes in relation to the other traditional HLA genes and a selected group of MHC class III genes. A total of 150 healthy Finnish individuals were included in the study. Subjects were genotyped for HLA alleles (HLA-A, -B, -DRB1, -DQB1, and -DPB1). The polymorphism of TNF, LTA, C4, BTNL2 and HLA-DRA genes was studied with 74 SNPs (single nucleotide polymorphism). The C4A and C4B gene copy numbers and a 2-bp silencing insertion at exon 29 in C4A gene were analysed with quantitative genomic realtime-PCR. The allele frequencies for each locus were calculated and haplotypes were constructed using both the traditional HLA alleles and SNP blocks. The most frequent Finnish A∼B∼DR -haplotype, uncommon in elsewhere in Europe, was A*03∼B*35∼DRB1*01∶01. The second most common haplotype was a common European ancestral haplotype AH 8.1 (A*01∼B*08∼DRB1*03∶01). Extended haplotypes containing HLA-B, TNF block, C4 and HLA-DPB1 strongly increased the number of HLA-DRB1 haplotypes showing variability in the extended HLA-DRB1 haplotype structures. On the contrary, BTNL2 block and HLA-DQB1 were more conserved showing linkage with the HLA-DRB1 alleles. We show that the use of HLA-DRB1 haplotypes rather than single HLA-DRB1 alleles is advantageous when studying the polymorphisms and LD patters of the MHC region. For disease association studies the HLA-DRB1 haplotypes with various MHC markers allows us to cluster haplotypes with functionally important gene variants such as C4 deficiency and cytokines TNF and LTA, and provides hypotheses for further assessment. Our study corroborates the importance of studying population-specific MHC

  11. Analysis of Swine Leukocyte Antigen Haplotypes in Yucatan Miniature Pigs Used as Biomedical Model Animal.

    PubMed

    Choi, Nu-Ri; Seo, Dong-Won; Choi, Ki-Myung; Ko, Na-Young; Kim, Ji-Ho; Kim, Hyun-Il; Jung, Woo-Young; Lee, Jun-Heon

    2016-03-01

    The porcine major histocompatibility complex (MHC) is called swine leukocyte antigen (SLA), which controls immune responses and transplantation reactions. The SLA is mapped on pig chromosome 7 (SSC7) near the centromere. In this study, 3 class I (SLA-1, SLA-3, and SLA-2) and 3 class II (DRB1, DQB1, and DQA) genes were used for investigation of SLA haplotypes in Yucatan miniature pigs in Korea. This pig breed is a well-known model organism for biomedical research worldwide. The current study indicated that Korean Yucatan pig population had 3 Class I haplotypes (Lr-4.0, Lr-6.0, and Lr-25.0) and 3 class II haplotypes (Lr-0.5, Lr-0.7, and Lr-0.25). The combinations of SLA class I and II haplotype together, 2 homozygous (Lr-4.5/4.5 and Lr-6.7/6.7) and 3 heterozygous (Lr-4.5/6.7, Lr-4.5/25.25, and Lr-6.7/25.25) haplotypes were identified, including previously unidentified new heterozygous haplotypes (Lr-4.5/4.7). In addition, a new SLA allele typing method using Agilent 2100 bioanalyzer was developed that permitted more rapid identification of SLA haplotypes. These results will facilitate the breeding of SLA homozygous Yucatan pigs and will expedite the possible use of these pigs for the biomedical research, especially xenotransplantation research. PMID:26950861

  12. KIR haplotypes are associated with late-onset type 1 diabetes in European–American families

    PubMed Central

    Traherne, J A; Jiang, W; Valdes, A M; Hollenbach, J A; Jayaraman, J; Lane, J A; Johnson, C; Trowsdale, J; Noble, J A

    2016-01-01

    Classical human leukocyte antigens (HLA) genes confer the strongest, but not the only, genetic susceptibility to type 1 diabetes. Killer cell immunoglobulin-like receptors (KIR), on natural killer (NK) cells, bind ligands including class I HLA. We examined presence or absence, with copy number, of KIR loci in 1698 individuals, from 339 multiplex type 1 diabetes families, from the Human Biological Data Interchange, previously genotyped for HLA. Combining family data with KIR copy number information allowed assignment of haplotypes using identity by descent. This is the first disease study to use KIR copy number typing and unambiguously define haplotypes by gene transmission. KIR A1 haplotypes were positively associated with T1D in the subset of patients without the high T1D risk HLA genotype, DR3/DR4 (odds ratio=1.29, P=0.0096). The data point to a role for KIR in type 1 diabetes risk in late-onset patients. In the top quartile (age of onset>14), KIR A2 haplotype was overtransmitted (63.4%, odds ratio=1.73, P=0.024) and KIR B haplotypes were undertransmitted (41.1%, odds ratio=0.70, P=0.0052) to patients. The data suggest that inhibitory ‘A' haplotypes are predisposing and stimulatory ‘B' haplotypes confer protection in both DR3/DR4-negative and late-onset patient groups. PMID:26492518

  13. Massively parallel haplotyping on microscopic beads for the high-throughput phase analysis of single molecules.

    PubMed

    Boulanger, Jérôme; Muresan, Leila; Tiemann-Boege, Irene

    2012-01-01

    In spite of the many advances in haplotyping methods, it is still very difficult to characterize rare haplotypes in tissues and different environmental samples or to accurately assess the haplotype diversity in large mixtures. This would require a haplotyping method capable of analyzing the phase of single molecules with an unprecedented throughput. Here we describe such a haplotyping method capable of analyzing in parallel hundreds of thousands single molecules in one experiment. In this method, multiple PCR reactions amplify different polymorphic regions of a single DNA molecule on a magnetic bead compartmentalized in an emulsion drop. The allelic states of the amplified polymorphisms are identified with fluorescently labeled probes that are then decoded from images taken of the arrayed beads by a microscope. This method can evaluate the phase of up to 3 polymorphisms separated by up to 5 kilobases in hundreds of thousands single molecules. We tested the sensitivity of the method by measuring the number of mutant haplotypes synthesized by four different commercially available enzymes: Phusion, Platinum Taq, Titanium Taq, and Phire. The digital nature of the method makes it highly sensitive to detecting haplotype ratios of less than 1:10,000. We also accurately quantified chimera formation during the exponential phase of PCR by different DNA polymerases. PMID:22558329

  14. An Extensive Analysis of Y-Chromosomal Microsatellite Haplotypes in Globally Dispersed Human Populations

    PubMed Central

    Kayser, Manfred; Krawczak, Michael; Excoffier, Laurent; Dieltjes, Patrick; Corach, Daniel; Pascali, Vincente; Gehrig, Christian; Bernini, Luigi F.; Jespersen, Jørgen; Bakker, Egbert; Roewer, Lutz; de Knijff, Peter

    2001-01-01

    The genetic variance at seven Y-chromosomal microsatellite loci (or short tandem repeats [STRs]) was studied among 986 male individuals from 20 globally dispersed human populations. A total of 598 different haplotypes were observed, of which 437 (73.1%) were each found in a single male only. Population-specific haplotype-diversity values were .86–.99. Analyses of haplotype diversity and population-specific haplotypes revealed marked population-structure differences between more-isolated indigenous populations (e.g., Central African Pygmies or Greenland Inuit) and more-admixed populations (e.g., Europeans or Surinamese). Furthermore, male individuals from isolated indigenous populations shared haplotypes mainly with male individuals from their own population. By analysis of molecular variance, we found that 76.8% of the total genetic variance present among these male individuals could be attributed to genetic differences between male individuals who were members of the same population. Haplotype sharing between populations, ΦST statistics, and phylogenetic analysis identified close genetic affinities among European populations and among New Guinean populations. Our data illustrate that Y-chromosomal STR haplotypes are an ideal tool for the study of the genetic affinities between groups of male subjects and for detection of population structure. PMID:11254455

  15. Analysis of Swine Leukocyte Antigen Haplotypes in Yucatan Miniature Pigs Used as Biomedical Model Animal

    PubMed Central

    Choi, Nu-Ri; Seo, Dong-Won; Choi, Ki-Myung; Ko, Na-Young; Kim, Ji-Ho; Kim, Hyun-Il; Jung, Woo-Young; Lee, Jun-Heon

    2016-01-01

    The porcine major histocompatibility complex (MHC) is called swine leukocyte antigen (SLA), which controls immune responses and transplantation reactions. The SLA is mapped on pig chromosome 7 (SSC7) near the centromere. In this study, 3 class I (SLA-1, SLA-3, and SLA-2) and 3 class II (DRB1, DQB1, and DQA) genes were used for investigation of SLA haplotypes in Yucatan miniature pigs in Korea. This pig breed is a well-known model organism for biomedical research worldwide. The current study indicated that Korean Yucatan pig population had 3 Class I haplotypes (Lr-4.0, Lr-6.0, and Lr-25.0) and 3 class II haplotypes (Lr-0.5, Lr-0.7, and Lr-0.25). The combinations of SLA class I and II haplotype together, 2 homozygous (Lr-4.5/4.5 and Lr-6.7/6.7) and 3 heterozygous (Lr-4.5/6.7, Lr-4.5/25.25, and Lr-6.7/25.25) haplotypes were identified, including previously unidentified new heterozygous haplotypes (Lr-4.5/4.7). In addition, a new SLA allele typing method using Agilent 2100 bioanalyzer was developed that permitted more rapid identification of SLA haplotypes. These results will facilitate the breeding of SLA homozygous Yucatan pigs and will expedite the possible use of these pigs for the biomedical research, especially xenotransplantation research. PMID:26950861

  16. Identification and genetic effect of haplotype in the bovine BMP7 gene.

    PubMed

    Huang, Yong-Zhen; Wang, Xin-Lei; He, Hua; Lan, Xian-Yong; Lei, Chu-Zhao; Zhang, Chun-Lei; Chen, Hong

    2013-12-15

    Bone morphogenetic proteins (BMPs) are peptide growth factors belonging to the transforming growth factor-beta (TGF-β) superfamily, and some members of the BMP family support white adipocyte differentiation. In this study, we focused on the BMP7 which singularly promotes the differentiation of brown preadipocytes. Haplotypes involving 5 single nucleotide polymorphism (SNP) sites in the bovine BMP7 gene were identified and their effect on body weight was analyzed. 16 haplotypes and 18 combined haplotypes were revealed and the linkage disequilibrium was assessed in the cattle population with 602 individuals representing three main cattle breeds from China. The results showed that haplotypes 3, 10 and 14 were predominant and accounted for 75.64%, 69.85%, and 83.36% in Nanyang, Qinchuan and Jiaxian cattle breeds, respectively. The statistical analyses indicated that the SNP 1, 4, and 5 are associated with the body weight, body length, and heart girth at 12 and 24 months in Nanyang cattle population (P<0.05), whereas there is no significant association between their 16 haplotypes and 18 combined haplotypes. Our results provide evidence that some SNPs and haplotypes in BMP7 are associated with growth traits, and may be utilized as a genetic marker in marker-assisted selection for beef cattle breeding programs. PMID:23500594

  17. Practical interpretation of CYP2D6 haplotypes: Comparison and integration of automated and expert calling.

    PubMed

    Ruaño, Gualberto; Kocherla, Mohan; Graydon, James S; Holford, Theodore R; Makowski, Gregory S; Goethe, John W

    2016-05-01

    We describe a population genetic approach to compare samples interpreted with expert calling (EC) versus automated calling (AC) for CYP2D6 haplotyping. The analysis represents 4812 haplotype calls based on signal data generated by the Luminex xMap analyzers from 2406 patients referred to a high-complexity molecular diagnostics laboratory for CYP450 testing. DNA was extracted from buccal swabs. We compared the results of expert calls (EC) and automated calls (AC) with regard to haplotype number and frequency. The ratio of EC to AC was 1:3. Haplotype frequencies from EC and AC samples were convergent across haplotypes, and their distribution was not statistically different between the groups. Most duplications required EC, as only expansions with homozygous or hemizygous haplotypes could be automatedly called. High-complexity laboratories can offer equivalent interpretation to automated calling for non-expanded CYP2D6 loci, and superior interpretation for duplications. We have validated scientific expert calling specified by scoring rules as standard operating procedure integrated with an automated calling algorithm. The integration of EC with AC is a practical strategy for CYP2D6 clinical haplotyping. PMID:26908082

  18. The effect of MAPT haplotype on neocortical Lewy body pathology in Parkinson disease.

    PubMed

    Robakis, Daphne; Cortes, Etty; Clark, Lorraine N; Vonsattel, Jean Paul G; Virmani, Tuhin; Alcalay, Roy N; Crary, John F; Levy, Oren A

    2016-06-01

    The H1 haplotype of the microtubule-associated protein tau gene (MAPT) is associated with an increased risk of Parkinson disease (PD) compared with the H2 haplotype, but its effect on Lewy body (LB) formation is unclear. In this study, we compared the MAPT haplotype frequency between pathologically confirmed PD patients (n = 71) and controls (n = 52). We analyzed Braak LB stage, Braak neurofibrillary tangle (NFT) stage, and CERAD amyloid score by haplotype. We further tested the association between MAPT haplotype and semi-quantitative counts of LBs, NFTs, and neuritic plaques (NPs) in multiple neocortical regions. Consistent with previous reports, PD cases had an increased likelihood of carrying an H1/H1 genotype compared to controls (OR = 5.72, 95 % CI 1.80-18.21, p = 0.003). Braak LB, Braak NFT and CERAD scores did not differ by haplotype. However, H1/H1 carriers had higher LB counts in parietal cortex (p = 0.02) and in overall neocortical LBs (p = 0.03) compared to non-H1/H1 cases. Our analyses suggest that PD patients homozygous for the H1 haplotype have a higher burden of neocortical LB pathology. PMID:27098667

  19. Predicting childhood effortful control from interactions between early parenting quality and children's dopamine transporter gene haplotypes.

    PubMed

    Li, Yi; Sulik, Michael J; Eisenberg, Nancy; Spinrad, Tracy L; Lemery-Chalfant, Kathryn; Stover, Daryn A; Verrelli, Brian C

    2016-02-01

    Children's observed effortful control (EC) at 30, 42, and 54 months (n = 145) was predicted from the interaction between mothers' observed parenting with their 30-month-olds and three variants of the solute carrier family C6, member 3 (SLC6A3) dopamine transporter gene (single nucleotide polymorphisms in intron8 and intron13, and a 40 base pair variable number tandem repeat [VNTR] in the 3'-untranslated region [UTR]), as well as haplotypes of these variants. Significant moderating effects were found. Children without the intron8-A/intron13-G, intron8-A/3'-UTR VNTR-10, or intron13-G/3'-UTR VNTR-10 haplotypes (i.e., haplotypes associated with the reduced SLC6A3 gene expression and thus lower dopamine functioning) appeared to demonstrate altered levels of EC as a function of maternal parenting quality, whereas children with these haplotypes demonstrated a similar EC level regardless of the parenting quality. Children with these haplotypes demonstrated a trade-off, such that they showed higher EC, relative to their counterparts without these haplotypes, when exposed to less supportive maternal parenting. The findings revealed a diathesis-stress pattern and suggested that different SLC6A3 haplotypes, but not single variants, might represent different levels of young children's sensitivity/responsivity to early parenting. PMID:25924976

  20. A TNF region haplotype offers protection from typhoid fever in Vietnamese patients

    PubMed Central

    2009-01-01

    The genomic region surrounding the TNF locus on human chromosome 6 has previously been associated with typhoid fever in Vietnam. We used a haplotypic approach to understand this association further. Eighty single nucleotide polymorphisms (SNPs) spanning a 150 kb region were genotyped in 95 Vietnamese individuals (typhoid case/mother/father trios). A subset of data from 33 SNPs with a minor allele frequency of >4.3% was used to construct haplotypes. Fifteen SNPs, which tagged the 42 constructed haplotypes were selected. The haplotype tagging SNPs (T1-T15) were genotyped in 380 confirmed typhoid cases and 380 Vietnamese ethnically matched controls. Allelic frequencies of seven SNPs (T1, T2, T3, T5, T6, T7, T8) were significantly different between typhoid cases and controls. Logistic regression results support the hypothesis that there is just one signal associated with disease at this locus. Haplotype-based analysis of the tag SNPs provided positive evidence of association with typhoid (posterior probability 0.821). The analysis highlighted a low-risk cluster of haplotypes that each carry the minor allele of T1 or T7, but not both, and otherwise carry the combination of alleles *12122*1111 at T1-T11, further supporting the one associated signal hypothesis. Finally, individuals that carry the typhoid fever protective haplotype *12122*1111 also produce a relatively low TNF-α response to LPS. PMID:17503085