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Sample records for identify human remains

  1. [PALEOPATHOLOGY OF HUMAN REMAINS].

    Science.gov (United States)

    Minozzi, Simona; Fornaciari, Gino

    2015-01-01

    Many diseases induce alterations in the human skeleton, leaving traces of their presence in ancient remains. Paleopathological examination of human remains not only allows the study of the history and evolution of the disease, but also the reconstruction of health conditions in the past populations. This paper describes the most interesting diseases observed in skeletal samples from the Roman Imperial Age necropoles found in urban and suburban areas of Rome during archaeological excavations in the last decades. The diseases observed were grouped into the following categories: articular diseases, traumas, infections, metabolic or nutritional diseases, congenital diseases and tumours, and some examples are reported for each group. Although extensive epidemiological investigation in ancient skeletal records is impossible, the palaeopathological study allowed to highlight the spread of numerous illnesses, many of which can be related to the life and health conditions of the Roman population.

  2. An investigation by LA-ICP-MS of possum tooth enamel as a model for identifying childhood geographical locations of historical and archaeological human remains from New Zealand

    International Nuclear Information System (INIS)

    Cameron, N.E.; Balks, M.; Littler, R.; Manley-Harris, M.; Te Awekotuku, N.

    2012-01-01

    LA-ICP-MS (laser ablation-inductively coupled plasma-mass spectrometry) has been used to analyse enamel from the teeth of brushtail possum (Trichosurus vulpecula) in order to model a method for identifying the childhood geographical origin of human remains within New Zealand. The model application of the method is promising for establishing locations of historical and archaeological human remains, including preserved heads, upoko tuhi. (author). 30 refs., 5 figs., 6 tabs.

  3. Kadav Moun PSA (:60) (Human Remains)

    Centers for Disease Control (CDC) Podcasts

    2010-02-18

    This is an important public health announcement about safety precautions for those handling human remains. Language: Haitian Creole.  Created: 2/18/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 2/18/2010.

  4. The Human Remains from HMS Pandora

    Directory of Open Access Journals (Sweden)

    D.P. Steptoe

    2002-04-01

    Full Text Available In 1977 the wreck of HMS Pandora (the ship that was sent to re-capture the Bounty mutineers was discovered off the north coast of Queensland. Since 1983, the Queensland Museum Maritime Archaeology section has carried out systematic excavation of the wreck. During the years 1986 and 1995-1998, more than 200 human bone and bone fragments were recovered. Osteological investigation revealed that this material represented three males. Their ages were estimated at approximately 17 +/-2 years, 22 +/-3 years and 28 +/-4 years, with statures of 168 +/-4cm, 167 +/-4cm, and 166cm +/-3cm respectively. All three individuals were probably Caucasian, although precise determination of ethnicity was not possible. In addition to poor dental hygiene, signs of chronic diseases suggestive of rickets and syphilis were observed. Evidence of spina bifida was seen on one of the skeletons, as were other skeletal anomalies. Various taphonomic processes affecting the remains were also observed and described. Compact bone was observed under the scanning electron microscope and found to be structurally coherent. Profiles of the three skeletons were compared with historical information about the 35 men lost with the ship, but no precise identification could be made. The investigation did not reveal the cause of death. Further research, such as DNA analysis, is being carried out at the time of publication.

  5. Human bovine tuberculosis - remains in the differential.

    LENUS (Irish Health Repository)

    Bilal, Shaukat

    2010-11-01

    Mycobacterium bovis is a pathogen of cattle. The unpasteurized milk of affected cattle is a source of infection in humans. Despite the screening of cattle and the pasteurization of milk, M bovis has not been eradicated. A high index of clinical suspicion is needed in symptomatic patients with a history of possible exposure. At risk groups include animal workers, farmers, meat packers, vets and zoo keepers. Humans are usually infected by the aerosol route. We present two cases of human bovine tuberculosis. One was a presumptive case and the second was a confirmed case. Both responded well to antituberculous therapy. In the confirmed case, there was evidence of transmission to the partner living in the same house. Rifampicin prophylaxis was given to the exposed case. The M. bovis from the confirmed case was isoniazid resistant, in addition to having the well known resistance to pyrazinamide. Isoniazid resistance has been described before in those who are immunocompromised. We describe it in an immunocompetent patient.

  6. Recovery of human remains after shark attack.

    Science.gov (United States)

    Byard, Roger W; James, Ross A; Heath, Karen J

    2006-09-01

    Two cases of fatal shark attack are reported where the only tissues recovered were fragments of lung. Case 1: An 18-year-old male who was in the sea behind a boat was observed by friends to be taken by a great white shark (Carcharodon carcharias). The shark dragged him under the water and then, with a second shark, dismembered the body. Witnesses noted a large amount of blood and unrecognizable body parts coming to the surface. The only tissues recovered despite an intensive beach and sea search were 2 fragments of lung. Case 2: A 19-year-old male was attacked by a great white shark while diving. A witness saw the shark swim away with the victim's body in its mouth. Again, despite intensive beach and sea searches, the only tissue recovered was a single piece of lung, along with pieces of wetsuit and diving equipment. These cases indicate that the only tissue to escape being consumed or lost in fatal shark attacks, where there is a significant attack with dismemberment and disruption of the integrity of the body, may be lung. The buoyancy of aerated pulmonary tissue ensures that it rises quickly to the surface, where it may be recovered by searchers soon after the attack. Aeration of the lung would be in keeping with death from trauma rather than from drowning and may be a useful marker in unwitnessed deaths to separate ante- from postmortem injury, using only relatively small amounts of tissues. Early organ recovery enhances the identification of human tissues as the extent of morphologic alterations by putrefactive processes and sea scavengers will have been minimized. DNA testing is also possible on such recovered fragments, enabling confirmation of the identity of the victim.

  7. Postmortem Scavenging of Human Remains by Domestic Cats

    Directory of Open Access Journals (Sweden)

    Ananya Suntirukpong, M.D.

    2017-11-01

    Full Text Available Objective: Crime scene investigators, forensic medicine doctors and pathologists, and forensic anthropologists frequently encounter postmortem scavenging of human remains by household pets. Case presentation: The authors present a case report of a partially skeletonized adult male found dead after more than three months in his apartment in Thailand. The body was in an advanced stage of decomposition with nearly complete skeletonization of the head, neck, hands, and feet. The presence of maggots and necrophagous (flesh eating beetles on the body confirmed that insects had consumed much of the soft tissues. Examination of the hand and foot bones revealed canine tooth puncture marks. Evidence of chewing indicated that one or more of the decedent’s three house cats had fed on the body after death. Recognizing and identifying carnivore and rodent activity on the soft flesh and bones of human remains is important in interpreting and reconstructing postmortem damage. Thorough analysis may help explain why skeletal elements are missing, damaged, or out of anatomical position. Conclusion: This report presents a multi-disciplinary approach combining forensic anthropology and forensic medicine in examining and interpreting human remains.

  8. Palmar, Patellar, and Pedal Human Remains from Pavlov

    Czech Academy of Sciences Publication Activity Database

    Trinkaus, E.; Wojtal, P.; Wilczyński, J.; Sázelová, Sandra; Svoboda, Jiří

    2017-01-01

    Roč. 2017, June (2017), s. 73-101 ISSN 1545-0031 Institutional support: RVO:68081758 Keywords : Gravettian * human remains * isolated bones * anatomically modern humans * Upper Paleolithic Subject RIV: AC - Archeology, Anthropology, Ethnology OBOR OECD: Archaeology http://paleoanthro.org/media/journal/content/PA20170073.pdf

  9. Forensic considerations when dealing with incinerated human dental remains.

    Science.gov (United States)

    Reesu, Gowri Vijay; Augustine, Jeyaseelan; Urs, Aadithya B

    2015-01-01

    Establishing the human dental identification process relies upon sufficient post-mortem data being recovered to allow for a meaningful comparison with ante-mortem records of the deceased person. Teeth are the most indestructible components of the human body and are structurally unique in their composition. They possess the highest resistance to most environmental effects like fire, desiccation, decomposition and prolonged immersion. In most natural as well as man-made disasters, teeth may provide the only means of positive identification of an otherwise unrecognizable body. It is imperative that dental evidence should not be destroyed through erroneous handling until appropriate radiographs, photographs, or impressions can be fabricated. Proper methods of physical stabilization of incinerated human dental remains should be followed. The maintenance of integrity of extremely fragile structures is crucial to the successful confirmation of identity. In such situations, the forensic dentist must stabilise these teeth before the fragile remains are transported to the mortuary to ensure preservation of possibly vital identification evidence. Thus, while dealing with any incinerated dental remains, a systematic approach must be followed through each stage of evaluation of incinerated dental remains to prevent the loss of potential dental evidence. This paper presents a composite review of various studies on incinerated human dental remains and discusses their impact on the process of human identification and suggests a step by step approach. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  10. Direct dating of Early Upper Palaeolithic human remains from Mladec.

    Science.gov (United States)

    Wild, Eva M; Teschler-Nicola, Maria; Kutschera, Walter; Steier, Peter; Trinkaus, Erik; Wanek, Wolfgang

    2005-05-19

    The human fossil assemblage from the Mladec Caves in Moravia (Czech Republic) has been considered to derive from a middle or later phase of the Central European Aurignacian period on the basis of archaeological remains (a few stone artefacts and organic items such as bone points, awls, perforated teeth), despite questions of association between the human fossils and the archaeological materials and concerning the chronological implications of the limited archaeological remains. The morphological variability in the human assemblage, the presence of apparently archaic features in some specimens, and the assumed early date of the remains have made this fossil assemblage pivotal in assessments of modern human emergence within Europe. We present here the first successful direct accelerator mass spectrometry radiocarbon dating of five representative human fossils from the site. We selected sample materials from teeth and from one bone for 14C dating. The four tooth samples yielded uncalibrated ages of approximately 31,000 14C years before present, and the bone sample (an ulna) provided an uncertain more-recent age. These data are sufficient to confirm that the Mladec human assemblage is the oldest cranial, dental and postcranial assemblage of early modern humans in Europe and is therefore central to discussions of modern human emergence in the northwestern Old World and the fate of the Neanderthals.

  11. 76 FR 14057 - Notice of Inventory Completion: University of Wyoming, Anthropology Department, Human Remains...

    Science.gov (United States)

    2011-03-15

    ...: University of Wyoming, Anthropology Department, Human Remains Repository, Laramie, WY AGENCY: National Park... Anthropology Department, Human Remains Repository, Laramie, WY. The human remains and associated funerary... the human remains was made by University of Wyoming, Anthropology Department, Human Remains Repository...

  12. Differential Decomposition Among Pig, Rabbit, and Human Remains.

    Science.gov (United States)

    Dautartas, Angela; Kenyhercz, Michael W; Vidoli, Giovanna M; Meadows Jantz, Lee; Mundorff, Amy; Steadman, Dawnie Wolfe

    2018-03-30

    While nonhuman animal remains are often utilized in forensic research to develop methods to estimate the postmortem interval, systematic studies that directly validate animals as proxies for human decomposition are lacking. The current project compared decomposition rates among pigs, rabbits, and humans at the University of Tennessee's Anthropology Research Facility across three seasonal trials that spanned nearly 2 years. The Total Body Score (TBS) method was applied to quantify decomposition changes and calculate the postmortem interval (PMI) in accumulated degree days (ADD). Decomposition trajectories were analyzed by comparing the estimated and actual ADD for each seasonal trial and by fuzzy cluster analysis. The cluster analysis demonstrated that the rabbits formed one group while pigs and humans, although more similar to each other than either to rabbits, still showed important differences in decomposition patterns. The decomposition trends show that neither nonhuman model captured the pattern, rate, and variability of human decomposition. © 2018 American Academy of Forensic Sciences.

  13. A method for defleshing human remains using household bleach.

    Science.gov (United States)

    Mann, Robert W; Berryman, Hugh E

    2012-03-01

    Medical examiners and forensic anthropologists are often faced with the difficult task of removing soft tissue from the human skeleton without damaging the bones, teeth and, in some cases, cartilage. While there are a number of acceptable methods that can be used to remove soft tissue including macerating in water, simmering or boiling, soaking in ammonia, removing with scissors, knife, scalpel or stiff brush, and dermestid beetles, each has its drawback in time, safety, or potential to damage bone. This technical report using the chest plate of a stabbing victim presents a safe and effective alternative method for removing soft tissue from human remains, in particular the chest plate, following autopsy, without damaging or separating the ribs, sternum, and costal cartilage. This method can be used to reveal subtle blunt force trauma to bone, slicing and stabbing injuries, and other forms of trauma obscured by overlying soft tissue. Despite the published cautionary notes, when done properly household bleach (3-6% sodium hypochlorite) is a quick, safe, and effective method for examining cartilage and exposing skeletal trauma by removing soft tissue from human skeletal remains. 2011 American Academy of Forensic Sciences. Published 2011. This article is a U.S. Government work and is in the public domain in the U.S.A.

  14. Duplex Alu Screening for Degraded DNA of Skeletal Human Remains

    Directory of Open Access Journals (Sweden)

    Fabian Haß

    2017-10-01

    Full Text Available The human-specific Alu elements, belonging to the class of Short INterspersed Elements (SINEs, have been shown to be a powerful tool for population genetic studies. An earlier study in this department showed that it was possible to analyze Alu presence/absence in 3000-year-old skeletal human remains from the Bronze Age Lichtenstein cave in Lower Saxony, Germany. We developed duplex Alu screening PCRs with flanking primers for two Alu elements, each combined with a single internal Alu primer. By adding an internal primer, the approximately 400–500 bp presence signals of Alu elements can be detected within a range of less than 200 bp. Thus, our PCR approach is suited for highly fragmented ancient DNA samples, whereas NGS analyses frequently are unable to handle repetitive elements. With this analysis system, we examined remains of 12 individuals from the Lichtenstein cave with different degrees of DNA degradation. The duplex PCRs showed fully informative amplification results for all of the chosen Alu loci in eight of the 12 samples. Our analysis system showed that Alu presence/absence analysis is possible in samples with different degrees of DNA degradation and it reduces the amount of valuable skeletal material needed by a factor of four, as compared with a singleplex approach.

  15. Fossil human remains from Bolomor Cave (Valencia, Spain).

    Science.gov (United States)

    Arsuaga, Juan Luis; Fernández Peris, Josep; Gracia-Téllez, Ana; Quam, Rolf; Carretero, José Miguel; Barciela González, Virginia; Blasco, Ruth; Cuartero, Felipe; Sañudo, Pablo

    2012-05-01

    Systematic excavations carried out since 1989 at Bolomor Cave have led to the recovery of four Pleistocene human fossil remains, consisting of a fibular fragment, two isolated teeth, and a nearly complete adult parietal bone. All of these specimens date to the late Middle and early Late Pleistocene (MIS 7-5e). The fibular fragment shows thick cortical bone, an archaic feature found in non-modern (i.e. non-Homo sapiens) members of the genus Homo. Among the dental remains, the lack of a midtrigonid crest in the M(1) represents a departure from the morphology reported for the majority of Neandertal specimens, while the large dimensions and pronounced shoveling of the marginal ridges in the C(1) are similar to other European Middle and late Pleistocene fossils. The parietal bone is very thick, with dimensions that generally fall above Neandertal fossils and resemble more closely the Middle Pleistocene Atapuerca (SH) adult specimens. Based on the presence of archaic features, all the fossils from Bolomor are attributed to the Neandertal evolutionary lineage. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Mummified remains from the Archaeological Museum in Zagreb, Croatia - Reviewing peculiarities and limitations of human and non-human radiological identification and analysis in mummified remains.

    Science.gov (United States)

    Petaros, Anja; Janković, Ivor; Cavalli, Fabio; Ivanac, Gordana; Brkljačić, Boris; Čavka, Mislav

    2015-10-01

    Forensic protocols and medico-legal techniques are increasingly being employed in investigations of museological material. The final findings of such investigations may reveal interesting facts on historical figures, customs and habits, as well as provide meaningful data for forensic use. Herein we present a case review where forensic experts were requested to identify taxonomic affinities, stage of preservation and provide skeletal analysis of mummified non-human archaeological remains, and verify whether two mummified hands are human or not. The manuscript offers a short review on the process and particularities of radiological species identification, the impact of post-mortem changes in the analysis and imaging of mummified remains as well as the macroscopical interpretation of trauma, pathology and authenticity in mummified remains, which can all turn useful when dealing with forensic cases. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  17. Ethical Issues Surrounding the Use of Modern Human Remains for Research in South Africa.

    Science.gov (United States)

    Briers, N; Dempers, J J

    2017-02-01

    Chapter 8 of the South African National Health Act 61 of 2003 (NHA) that deals with the donation of human tissue was promulgated in 2012. The new Act is perceived to impose restrictions on low-risk research involving human remains. This study aimed to identify the issues raised by a research ethics committee (REC) when reviewing protocols where human remains are used as data source. REC minutes from 2009 to 2014 were reviewed, and issues raised by the committee were categorized. In total, 127 protocols submitted to the committee over 6 years involved human remains. Queries relating to science (22.2%) and administration (18.9%) were the most common, whereas queries relating to legal issues constituted only 10.2%. Ethical issues centered on informed consent regarding sensitive topics such as HIV, DNA, and deceased children. The change in legislation did not change the number or type of legal issues identified by the REC.

  18. 76 FR 14058 - Notice of Inventory Completion: University of Wyoming, Anthropology Department, Human Remains...

    Science.gov (United States)

    2011-03-15

    ...: University of Wyoming, Anthropology Department, Human Remains Repository, Laramie, WY AGENCY: National Park... in the possession and control of the University of Wyoming Anthropology Department, Human Remains... made by University of Wyoming, Anthropology Department, Human Remains Repository, professional staff in...

  19. The treatment of human remains | Satyapal | South African Journal ...

    African Journals Online (AJOL)

    South African Journal of Bioethics and Law ... surrounding Body Worlds' innovator, copycat competitor exhibitions, human rights violations and the legal vacuum within which anatomical specimens are permitted to cross international boarders are explored. ... Boundaries will be pushed only as far as society condones it.

  20. 75 FR 5108 - Notice of Inventory Completion: University of Wyoming, Anthropology Department, Human Remains...

    Science.gov (United States)

    2010-02-01

    ... Wyoming, Anthropology Department, Human Remains Repository, Laramie, WY AGENCY: National Park Service... funerary objects in the possession and control of the University of Wyoming, Anthropology Department, Human... of Wyoming, Anthropology Department, Human Remains Repository professional staff in consultation with...

  1. Identification of human remains from the Second World War mass graves uncovered in Bosnia and Herzegovina.

    Science.gov (United States)

    Marjanović, Damir; Hadžić Metjahić, Negra; Čakar, Jasmina; Džehverović, Mirela; Dogan, Serkan; Ferić, Elma; Džijan, Snježana; Škaro, Vedrana; Projić, Petar; Madžar, Tomislav; Rod, Eduard; Primorac, Dragan

    2015-06-01

    To present the results obtained in the identification of human remains from World War II found in two mass graves in Ljubuški, Bosnia and Herzegovina. Samples from 10 skeletal remains were collected. Teeth and femoral fragments were collected from 9 skeletons and only a femoral fragment from 1 skeleton. DNA was isolated from bone and teeth samples using an optimized phenol/chloroform DNA extraction procedure. All samples required a pre-extraction decalcification with EDTA and additional post-extraction DNA purification using filter columns. Additionally, DNA from 12 reference samples (buccal swabs from potential living relatives) was extracted using the Qiagen DNA extraction method. QuantifilerTM Human DNA Quantification Kit was used for DNA quantification. PowerPlex ESI kit was used to simultaneously amplify 15 autosomal short tandem repeat (STR) loci, and PowerPlex Y23 was used to amplify 23 Y chromosomal STR loci. Matching probabilities were estimated using a standard statistical approach. A total of 10 samples were processed, 9 teeth and 1 femoral fragment. Nine of 10 samples were profiled using autosomal STR loci, which resulted in useful DNA profiles for 9 skeletal remains. A comparison of established victims' profiles against a reference sample database yielded 6 positive identifications. DNA analysis may efficiently contribute to the identification of remains even seven decades after the end of the World War II. The significant percentage of positively identified remains (60%), even when the number of the examined possible living relatives was relatively small (only 12), proved the importance of cooperation with the members of the local community, who helped to identify the closest missing persons' relatives and collect referent samples from them.

  2. The clandestine multiple graves in Malaysia: The first mass identification operation of human skeletal remains.

    Science.gov (United States)

    Mohd Noor, Mohd Suhani; Khoo, Lay See; Zamaliana Alias, Wan Zafirah; Hasmi, Ahmad Hafizam; Ibrahim, Mohamad Azaini; Mahmood, Mohd Shah

    2017-09-01

    The first ever mass identification operation of skeletal remains conducted for the clandestine graves in Malaysia consisted of 165 individuals unearthed from 28 human trafficking transit camps located in Wang Kelian, along the Thai-Malaysia border. A DVI response was triggered in which expert teams comprising of pathologists, anthropologists, odontologists, radiologists and DNA experts were gathered at the identified operation centre. The Department of Forensic Medicine, Hospital Sultanah Bahiyah, Alor Star, Kedah, located approximately 75km away from Wang Kelian, was temporarily converted into a victim identification centre (VIC) as it is the nearest available forensic facility to the mass grave site. The mortuary operation was conducted over a period of 3 months from June to September 2015, and was divided into two phases; phase 1 involving the postmortem examination of the remains of 116 suspected individuals and for phase 2 the remains of 49 suspected individuals. The fact that the graves were of unknown individuals afforded the mass identification operation a sufficient duration of 2 weeks as preparatory phase enabling procedurals and daily victim identification workflow to be established, and the setting up of a temporary body storage for the designated mortuary. The temporary body storage has proven to be a significant factor in enabling the successful conclusion of the VIC operation to the final phase of temporary controlled burials. Recognition from two international observers, Mr. Andréas Patiño Umaña, from the International Committee of Red Cross (ICRC) and Prof. Noel Woodford from Victoria Institute of Forensic Medicine (VIFM) had proven the mortuary operation was in compliance to the international quality and standards. The overall victim identification and mortuary operation identified a number of significant challenges, in particular the management of commingled human remains as well as the compilation of postmortem data in the absence of

  3. "SINCE I MUST PLEASE THOSE BELOW": HUMAN SKELETAL REMAINS RESEARCH AND THE LAW.

    Science.gov (United States)

    Holland, Thomas D

    2015-01-01

    The ethics of non-invasive scientific research on human skeletal remains are poorly articulated and lack a single, definitive analogue in western law. Laws governing invasive research on human fleshed remains, as well as bio-ethical principles established for research on living subjects, provide effective models for the establishment of ethical guidelines for non-invasive research on human skeletal remains. Specifically, non-invasive analysis of human remains is permissible provided that the analysis and collection of resulting data (1) are accomplished with respect for the dignity of the individual, (2) do not violate the last-known desire of the deceased, (3) do not adversely impact the right of the next of kin to perform a ceremonious and decent disposal of the remains, and (4) do not unduly or maliciously violate the privacy interests of the next of kin.

  4. New paleoradiological investigations of ancient human remains from North West Lombardy archaeological excavations

    International Nuclear Information System (INIS)

    Licata, Marta; Borgo, Melania; Armocida, Giuseppe; Nicosia, Luca; Ferioli, Elena

    2016-01-01

    Since its birth in 1895, radiology has been used to study ancient mummies. The purpose of this article is to present paleoradiological investigations conducted on several medieval human remains in Varese province. Anthropological (generic identification) and paleopathological analyses were carried out with the support of diagnostic imaging (X-ray and CT scans). Human remains were discovered during excavations of medieval archaeological sites in northwest Lombardy. Classical physical anthropological methods were used for the macroscopic identification of the human remains. X-ray and CT scans were performed on the same scanner (16-layer Hitachi Eclos 16 X-ray equipment). Radiological analysis permitted investigating (1) the sex, (2) age of death, (3) type of trauma, (4) therapeutic interventions and (5) osteomas in ancient human remains. In particular, X-ray and CT examinations showed dimorphic facial traits on the mummified skull, and the same radiological approaches allowed determining the age at death from a mummified lower limb. CT analyses allow investigating different types of traumatic lesions in skulls and postcranial skeleton portions and reconstructing the gait and functional outcomes of a fractured femur. Moreover, one case of possible Gardner's syndrome (GS) was postulated from observing multiple osteomas in an ancient skull. Among the medical tests available to the clinician, radiology is the most appropriate first-line procedure for a diagnostic approach to ancient human remains because it can be performed without causing any significant damage to the specimen. (orig.)

  5. New paleoradiological investigations of ancient human remains from North West Lombardy archaeological excavations

    Energy Technology Data Exchange (ETDEWEB)

    Licata, Marta; Borgo, Melania; Armocida, Giuseppe; Nicosia, Luca; Ferioli, Elena [University of Insubria (Varese), Department of Biotechnology and Life Sciences, Varese (Italy)

    2016-03-15

    Since its birth in 1895, radiology has been used to study ancient mummies. The purpose of this article is to present paleoradiological investigations conducted on several medieval human remains in Varese province. Anthropological (generic identification) and paleopathological analyses were carried out with the support of diagnostic imaging (X-ray and CT scans). Human remains were discovered during excavations of medieval archaeological sites in northwest Lombardy. Classical physical anthropological methods were used for the macroscopic identification of the human remains. X-ray and CT scans were performed on the same scanner (16-layer Hitachi Eclos 16 X-ray equipment). Radiological analysis permitted investigating (1) the sex, (2) age of death, (3) type of trauma, (4) therapeutic interventions and (5) osteomas in ancient human remains. In particular, X-ray and CT examinations showed dimorphic facial traits on the mummified skull, and the same radiological approaches allowed determining the age at death from a mummified lower limb. CT analyses allow investigating different types of traumatic lesions in skulls and postcranial skeleton portions and reconstructing the gait and functional outcomes of a fractured femur. Moreover, one case of possible Gardner's syndrome (GS) was postulated from observing multiple osteomas in an ancient skull. Among the medical tests available to the clinician, radiology is the most appropriate first-line procedure for a diagnostic approach to ancient human remains because it can be performed without causing any significant damage to the specimen. (orig.)

  6. Decontamination and management of human remains following incidents of hazardous chemical release.

    Science.gov (United States)

    Hauschild, Veronique D; Watson, Annetta; Bock, Robert

    2012-01-01

    To provide specific guidance and resources for systematic and orderly decontamination of human remains resulting from a chemical terrorist attack or accidental chemical release. A detailed review and health-based decision criteria protocol is summarized. Protocol basis and logic are derived from analyses of compound-specific toxicological data and chemical/physical characteristics. Guidance is suitable for civilian or military settings where human remains potentially contaminated with hazardous chemicals may be present, such as sites of transportation accidents, terrorist operations, or medical examiner processing points. Guidance is developed from data-characterizing controlled experiments with laboratory animals, fabrics, and materiel. Logic and specific procedures for decontamination and management of remains, protection of mortuary affairs personnel, and decision criteria to determine when remains are sufficiently decontaminated are presented. Established procedures as well as existing materiel and available equipment for decontamination and verification provide reasonable means to mitigate chemical hazards from chemically exposed remains. Unique scenarios such as those involving supralethal concentrations of certain liquid chemical warfare agents may prove difficult to decontaminate but can be resolved in a timely manner by application of the characterized systematic approaches. Decision criteria and protocols to "clear" decontaminated remains for transport and processing are also provided. Once appropriate decontamination and verification have been accomplished, normal procedures for management of remains and release can be followed.

  7. Evolutionary anthropology and genes: investigating the genetics of human evolution from excavated skeletal remains.

    Science.gov (United States)

    Anastasiou, Evilena; Mitchell, Piers D

    2013-10-01

    The development of molecular tools for the extraction, analysis and interpretation of DNA from the remains of ancient organisms (paleogenetics) has revolutionised a range of disciplines as diverse as the fields of human evolution, bioarchaeology, epidemiology, microbiology, taxonomy and population genetics. The paper draws attention to some of the challenges associated with the extraction and interpretation of ancient DNA from archaeological material, and then reviews the influence of paleogenetics on the field of human evolution. It discusses the main contributions of molecular studies to reconstructing the evolutionary and phylogenetic relationships between extinct hominins (human ancestors) and anatomically modern humans. It also explores the evidence for evolutionary changes in the genetic structure of anatomically modern humans in recent millennia. This breadth of research has led to discoveries that would never have been possible using traditional approaches to human evolution. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. 43 CFR 10.11 - Disposition of culturally unidentifiable human remains.

    Science.gov (United States)

    2010-10-01

    ... AMERICAN GRAVES PROTECTION AND REPATRIATION REGULATIONS Human Remains, Funerary Objects, Sacred Objects, or... religious leaders of all Indian tribes and Native Hawaiian organizations: (i) From whose tribal lands, at... objects; (ii) The names and appropriate methods to contact any traditional religious leaders who should be...

  9. Stratigraphy and chronology of the WLH 50 human remains, Willandra Lakes World Heritage Area, Australia.

    Science.gov (United States)

    Grün, Rainer; Spooner, Nigel; Magee, John; Thorne, Alan; Simpson, John; Yan, Ge; Mortimer, Graham

    2011-05-01

    We present a detailed description of the geological setting of the burial site of the WLH 50 human remains along with attempts to constrain the age of this important human fossil. Freshwater shells collected at the surface of Unit 3, which is most closely associated with the human remains, and a carbonate sample that encrusted the human bone were analysed. Gamma spectrometry was carried out on the WLH 50 calvaria and TIMS U-series analysis on a small post-cranial bone fragment. OSL dating was applied to a sample from Unit 3 at a level from which the WLH 50 remains may have eroded, as well as from the underlying sediments. Considering the geochemistry of the samples analysed, as well as the possibility of reworking or burial from younger layers, the age of the WLH 50 remains lies between 12.2 ± 1.8 and 32.8 ± 4.6 ka (2-σ errors). Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Occurrence of oriental flies associated with indoor and outdoor human remains in the tropical climate of north Malaysia.

    Science.gov (United States)

    Kumara, T K; Disney, R H L; Abu Hassan, A; Flores, Micah; Hwa, Tan Siew; Mohamed, Zulqarnain; CheSalmah, M R; Bhupinder, S

    2012-06-01

    Flies attracted to human remains during death investigations were surveyed in north Peninsular Malaysia. Six families, eight genera, and 16 species were identified from human remains, with the greatest fly diversity occurring on remains recovered indoors. The total relative frequency of species was led by Chrysomya megacephala (Fabricius, 1794) (46%), followed by Chrysomya rufifacies (Macquart, 1842) (22%), Sarcophaga (Liopygia) ruficornis (Fabricius, 1974) (5%), Sarcophaga spp. (4%), Synthesiomyia nudiseta Wulp, 1883 (6%), Megaselia spp. (3%), Megaselia scalaris (Loew, 1866), (2%), Megaselia spiracularis Schmitz, 1938 (2%), and Chrysomya villeneuvi Patton, 1922 (2%). Hemipyrellia tagaliana (Bigot, 1877), Desmometopa sp., Megaselia curtineura (Brues, 1909), Hemipyrellia ligurriens Wiedemann 1830, Ophyra sp., Sarcophaga princeps Wiedemann 1830, Piophila casei (Linnaeus, 1758), and unidentified pupae each represented 1%, respectively. © 2012 The Society for Vector Ecology.

  11. Indoors forensic entomology: colonization of human remains in closed environments by specific species of sarcosaprophagous flies.

    Science.gov (United States)

    Pohjoismäki, Jaakko L O; Karhunen, Pekka J; Goebeler, Sirkka; Saukko, Pekka; Sääksjärvi, Ilari E

    2010-06-15

    Fly species that are commonly recovered on human corpses concealed in houses or other dwellings are often dependent on human created environments and might have special features in their biology that allow them to colonize indoor cadavers. In this study we describe nine typical cases involving forensically relevant flies on human remains found indoors in southern Finland. Eggs, larvae and puparia were reared to adult stage and determined to species. Of the five species found the most common were Lucilia sericata Meigen, Calliphora vicina Robineau-Desvoidy and Protophormia terraenovae Robineau-Desvoidy. The flesh fly Sarcophaga caerulescens Zetterstedt is reported for the first time to colonize human cadavers inside houses and a COI gene sequence based DNA barcode is provided for it to help facilitate identification in the future. Fly biology, colonization speed and the significance of indoors forensic entomological evidence are discussed. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  12. An unusual discovery of human remains from the medieval church of Grevenmacher (Luxembourg).

    Science.gov (United States)

    Trautmann, Bernd; Bis-Worch, Christiane

    2017-12-01

    The occurrence of burned human remains on a Christian burial ground is very rare in medieval Europe. Therefore, the discovery of a complex consisting of commingled burned and unburned human bones within the church of Grevenmacher (Luxembourg) is from special interest for anthropological as well as archaeological research. In the current paper we present methods for a comprehensive analysis for such an exceptional case connected with the question if this bone accumulation represents a form of funerary custom or if other factors lead to its composition. Thereof, two possible scenarios for the occurrence of this unusual composition were created and discussed.

  13. The Insta-Dead: The rhetoric of the human remains trade on Instagram

    Directory of Open Access Journals (Sweden)

    Damien Huffer

    2017-07-01

    Full Text Available There is a thriving trade, and collector community, around human remains that is facilitated by posts on new social media such as Instagram, Facebook, Etsy, and, until recently, eBay. In this article, we examine several thousand Instagram posts and perform some initial text analysis on the language and rhetoric of these posts to understand something about the function of this community, what they value and how they trade, buy, and sell, human remains. Our results indicate a well-connected network of collectors and dealers both specialist and generalist, with a surprisingly wide-reaching impact on the 'enthusiasts' who, through their rhetoric, support the activities of this collecting community, in the face of legal and ethical issues generated by its existence.

  14. Enhanced Contaminated Human Remains Pouch: initial development and preliminary performance assessments

    Energy Technology Data Exchange (ETDEWEB)

    Iseli, A.M.; Kwen, H.D.; Ul-Alam, M.; Balasubramanian, M.; Rajagopalan, S.

    2011-11-07

    The objective is to produce a proof of concept prototype Enhanced Contaminated Human Remains Pouch (ECHRP) with self-decontamination capability to provide increased protection to emergency response personnel. The key objective was to decrease the concentration of toxic chemicals through the use of an absorbent and reactive nanocellulose liner. Additionally, nanomaterials with biocidal properties were developed and tested as a 'stand-alone' treatment. The setting was a private company research laboratory. The main outcome measures were production of a functional prototype. A functional prototype capable of mitigating the threats due to sulfur mustard, Soman, and a large variety of liquid and vapor toxic industrial chemicals was produced. Stand-alone biocidal treatment efficacy was validated. The ECHRP provides superior protection from both chemical and biological hazards to various emergency response personnel and human remains handlers.

  15. Inimluud Mihkli kiriku võlvidelt / Human remains on the vaulted ceiling of Mihkli Church

    Directory of Open Access Journals (Sweden)

    Martin Malve

    2012-01-01

    Full Text Available Altogether 4029 human bones or their fragments from the C 13th–18th were gathered and analysed from soil on the vaults of Mihkli (St Michael’s Church in western Estonia during the rescue works in 2011 (photo 1. Ribs and vertebrae formed the majority of bones, but wholly preserved long bones and other larger bones, as well as, hand and foot bones that are quite typical among mixed human remains were almost absent in this case. Therefore, it can be concluded that during the earthworks larger bones were taken from the soil. The minimum number of adults was determined by the ribs of the right side. Only the ribs with preserved heads (figure 1 were used in calculations. The rib fragments indicate approximately 60 adults among the assorted bones. Judging by the radius, there were at least 16 children among the bone assemblage. Scarceness of children in the Mihkli church can be the result of poor preservation, smallness and fragility of their bones, but the possibility that subadult (child and juvenile burials were fewer in the destroyed part of the churchyard cannot be ruled out.Pathological analysis of the osteological material ascertained several diseases and traumas, the most common pathologies being connected to ageing, for example, wearing of joints (Osteoarthrosis. Various diseases related to degeneration of the spine were present – spondylosis, spondyloarthrosis and osteochondrosis. Compression fractures (fractura compressiva and Schmorl´s nodes (nodi Schmorl indicated strenuous physical activity and/or traumas. Dental diseases included caries (photo 2, alveolar reduction, hypoplasia and tooth abscesses. Several upper and lower jaws showed traces of ante mortem lost teeth (photo 3. In one case a canine of the right mandible of an adult man (age 45 + years had formed but had not erupted (photo 4.Various healed fractures of ribs and limb bones formed the bulk of traumas detected on the bones. Three right ribs had fractures in a stage of

  16. Beneath the surface of water. Hydraulic structures and human skeletal remains in Ancient Italy

    Directory of Open Access Journals (Sweden)

    Vera Zanoni

    2013-12-01

    Full Text Available Recent findings from the area of Modena, in Northern Italy, have revitalized the debate on the association between human skeletal remains and artificial hydraulic structures. In this paper, our intention is to assemble the relevant archaeological and anthropological data on the matter in order to establish whether these findings are exceptional and isolated or indicate instead a structured and specific cultural behaviour which persists through time.

  17. A code of ethics for evidence-based research with ancient human remains.

    Science.gov (United States)

    Kreissl Lonfat, Bettina M; Kaufmann, Ina Maria; Rühli, Frank

    2015-06-01

    As clinical research constantly advances and the concept of evolution becomes a strong and influential part of basic medical research, the absence of a discourse that deals with the use of ancient human remains in evidence-based research is becoming unbearable. While topics such as exhibition and excavation of human remains are established ethical fields of discourse, when faced with instrumentalization of ancient human remains for research (i.e., ancient DNA extractions for disease marker analyses) the answers from traditional ethics or even more practical fields of bio-ethics or more specific biomedical ethics are rare to non-existent. The Centre for Evolutionary Medicine at the University of Zurich solved their needs for discursive action through the writing of a self-given code of ethics which was written in dialogue with the researchers at the Institute and was published online in Sept. 2011: http://evolutionäremedizin.ch/coe/. The philosophico-ethical basis for this a code of conduct and ethics and the methods are published in this article. © 2015 Wiley Periodicals, Inc.

  18. Human Remains from the Pleistocene-Holocene Transition of Southwest China Suggest a Complex Evolutionary History for East Asians

    Science.gov (United States)

    Curnoe, Darren; Xueping, Ji; Herries, Andy I. R.; Kanning, Bai; Taçon, Paul S. C.; Zhende, Bao; Fink, David; Yunsheng, Zhu; Hellstrom, John; Yun, Luo; Cassis, Gerasimos; Bing, Su; Wroe, Stephen; Shi, Hong; Parr, William C. H.; Shengmin, Huang; Rogers, Natalie

    2012-01-01

    Background Later Pleistocene human evolution in East Asia remains poorly understood owing to a scarcity of well described, reliably classified and accurately dated fossils. Southwest China has been identified from genetic research as a hotspot of human diversity, containing ancient mtDNA and Y-DNA lineages, and has yielded a number of human remains thought to derive from Pleistocene deposits. We have prepared, reconstructed, described and dated a new partial skull from a consolidated sediment block collected in 1979 from the site of Longlin Cave (Guangxi Province). We also undertook new excavations at Maludong (Yunnan Province) to clarify the stratigraphy and dating of a large sample of mostly undescribed human remains from the site. Methodology/Principal Findings We undertook a detailed comparison of cranial, including a virtual endocast for the Maludong calotte, mandibular and dental remains from these two localities. Both samples probably derive from the same population, exhibiting an unusual mixture of modern human traits, characters probably plesiomorphic for later Homo, and some unusual features. We dated charcoal with AMS radiocarbon dating and speleothem with the Uranium-series technique and the results show both samples to be from the Pleistocene-Holocene transition: ∼14.3-11.5 ka. Conclusions/Significance Our analysis suggests two plausible explanations for the morphology sampled at Longlin Cave and Maludong. First, it may represent a late-surviving archaic population, perhaps paralleling the situation seen in North Africa as indicated by remains from Dar-es-Soltane and Temara, and maybe also in southern China at Zhirendong. Alternatively, East Asia may have been colonised during multiple waves during the Pleistocene, with the Longlin-Maludong morphology possibly reflecting deep population substructure in Africa prior to modern humans dispersing into Eurasia. PMID:22431968

  19. Comparison of decomposition rates between autopsied and non-autopsied human remains.

    Science.gov (United States)

    Bates, Lennon N; Wescott, Daniel J

    2016-04-01

    Penetrating trauma has been cited as a significant factor in the rate of decomposition. Therefore, penetrating trauma may have an effect on estimations of time-since-death in medicolegal investigations and on research examining decomposition rates and processes when autopsied human bodies are used. The goal of this study was to determine if there are differences in the rate of decomposition between autopsied and non-autopsied human remains in the same environment. The purpose is to shed light on how large incisions, such as those from a thorocoabdominal autopsy, effect time-since-death estimations and research on the rate of decomposition that use both autopsied and non-autopsied human remains. In this study, 59 non-autopsied and 24 autopsied bodies were studied. The number of accumulated degree days required to reach each decomposition stage was then compared between autopsied and non-autopsied remains. Additionally, both types of bodies were examined for seasonal differences in decomposition rates. As temperature affects the rate of decomposition, this study also compared the internal body temperatures of autopsied and non-autopsied remains to see if differences between the two may be leading to differential decomposition. For this portion of this study, eight non-autopsied and five autopsied bodies were investigated. Internal temperature was collected once a day for two weeks. The results showed that differences in the decomposition rate between autopsied and non-autopsied remains was not statistically significant, though the average ADD needed to reach each stage of decomposition was slightly lower for autopsied bodies than non-autopsied bodies. There was also no significant difference between autopsied and non-autopsied bodies in the rate of decomposition by season or in internal temperature. Therefore, this study suggests that it is unnecessary to separate autopsied and non-autopsied remains when studying gross stages of human decomposition in Central Texas

  20. Skeletal Indicators of Shark Feeding on Human Remains: Evidence from Florida Forensic Anthropology Cases.

    Science.gov (United States)

    Stock, Michala K; Winburn, Allysha P; Burgess, George H

    2017-11-01

    This research examines a series of six Florida forensic anthropology cases that exhibit taphonomic evidence of marine deposition and shark-feeding activities. In each case, we analyzed patterns of trauma/damage on the skeletal remains (e.g., sharp-force bone gouges and punctures) and possible mechanisms by which they were inflicted during shark predation/scavenging. In some cases, shark teeth were embedded in the remains; in the absence of this evidence, we measured interdental distance from defects in the bone to estimate shark body length, as well as to draw inferences about the potential species responsible. We discuss similarities and differences among the cases and make comparisons to literature documenting diagnostic shark-inflicted damage to human remains from nearby regions. We find that the majority of cases potentially involve bull or tiger sharks scavenging the remains of previously deceased, adult male individuals. This scavenging results in a distinctive taphonomic signature including incised gouges in cortical bone. © 2017 American Academy of Forensic Sciences.

  1. Repair of human DNA in molecules that replicate or remain unreplicated following ultraviolet irradiation

    International Nuclear Information System (INIS)

    Waters, R.

    1980-01-01

    The extent of DNA replication, the incidence of uv induced pyrimidine dimers and the repair replication observed after their excision was monitored in human fibroblasts uv irradiated with single or split uv doses. The excision repair processes were measured in molecules that remained unreplicated or in those that replicated after the latter uv irradiation. Less DNA replication was observed after a split as opposed to single uv irradiation. Furthermore, a split dose did not modify the excision parameters measured after a single irradiation, regardless of whether the DNA had replicated or not

  2. Human cultural and related remains from Me Aure Cave (site WMD007), Moindou, New Caledonia

    International Nuclear Information System (INIS)

    Grant-Mackie, J.A.; Sand, C.; Valentin, F.; Fitzgerald, B.M.; Richer de Forges, B.

    2013-01-01

    In 1995 a small cave near Me Aure (site WMD007) on the west coast of New Caledonia, about 120 km northwest of Noumea, was excavated and found to contain mainly owl and human midden deposits. Some of the contents have already been documented and the present paper completes the study by reporting the human-related materials, including human bone fragments, pottery sherds, bones of four rodent species, and marine mollusc and crab remains. Each of these material classes are reported separately by the authors responsible for their analysis, and the results and interpretations based on each line of evidence are compared and contrasted. The human bone and pottery data suggest a temporally constrained deposit (2750-2350 BP) that has experienced stratigraphic disturbance. This result raises doubt about the un-mixed nature of the deposit emphasized in earlier publications and it urges instead the conclusion that the Me Aure stratigraphy consists mostly of a redeposited set of horizons. If this conclusion is correct, interpretations already published relying on a fixed chronology, especially about vegetation change and avifauna depletion or early aroid introduction will need to be reconsidered. The site constitutes the first in New Caledonia for which a cave deposit has now been fully analysed. (author). 36 refs., 11 figs., 9 tabs.

  3. Multiscale, multispectral and multitemporal satellite data to identify archaeological remains in the archaeological area of Tiwanaku (Bolivia)

    Science.gov (United States)

    Masini, Nicola; Lasaponara, Rosa

    2015-04-01

    The aim of this paper is to investigate the cultural landscape of the archaeological area of Tiwanaku (Bolivia) using multiscale, multispectral and multitemporal satellite data. Geospatial analysis techniques were applied to the satellite data sets in order to enhance and map traces of past human activities and perform a spatial characterization of environmental and cultural patterns. In particular, in the Tiwanaku area, the approach based on local indicators of spatial autocorrelation (LISA) applied to ASTER data allowed us to identify traces of a possible ancient hydrographic network with a clear spatial relation with the well-known moat surrounding the core of the monumental area. The same approach applied to QuickBird data, allowed us to identify numerous traces of archaeological interest, in Mollo Kontu mound, less investigated than the monumental area. Some of these traces were in perfect accordance with the results of independent studies, other were completely unknown. As a whole, the detected features, composing a geometric pattern with roughly North-South orientation, closely match those of the other residential contexts at Tiwanaku. These new insights, captured from multitemporal ASTER and QuickBird data processing, suggested new questions on the ancient landscape and provided important information for planning future field surveys and archaeogeophyical investigations. Reference [1] Lasaponara R., Masini N. 2014. Beyond modern landscape features: New insights in thearchaeological area of Tiwanaku in Bolivia from satellite data. International Journal of Applied Earth Observation and Geoinformation, 26, 464-471, http://dx.doi.org/10.1016/j.jag.2013.09.00. [2] Tapete D., Cigna F., Masini N., Lasaponara R. 2013. Prospection and monitoring of the archaeological heritage of Nasca, Peru, with ENVISAT ASAR, Archaeological Prospection, 20, 133-147, doi: 10.1002/arp.1449. [3] Lasaponara R, N Masini, 2012 Satellite Remote Sensing, A New Tool for Archaeology (Series

  4. Micromorphological Aspects of Forensic Geopedology: can vivianite be a marker of human remains permanence in soil?

    Science.gov (United States)

    Ern, Stephania Irmgard Elena; Trombino, Luca; Cattaneo, Cristina

    2010-05-01

    The number of death cases of forensic interest grows up every year. When decomposed or skeletal remains come out from the soil, the bones become of anthropological competence and the scene of crime become of soil specialists competence. The present study concerns real cases of buried/hidden remains in clandestine graves which have been studied in order to prove the permanence in soil even if the soil particles have been washed away or the body is no more buried. One hypothesis has been taken in account, related to the evidences of vivianite crystallization on the bones. The vivianite is an iron hydrate phosphate (Fe3(PO4)2·8(H2O)) that usually forms in anoxic, reducing and rich in organic matter conditions. In these conditions the iron in the soil is in reduced form (Fe2+) and associates with the phosphorous, present in the environment, as attested in archaeological contexts. Going back to the cases of buried/hidden remains, it is possible to state that the soil can be source of iron, while the bones can supply phosphorous and the decomposition process induces the anoxic/reducing conditions in the burial area. In this light, the presence of vivianite crystallizations on the bones could be a method to discriminate burial (i.e. permanence in soil) even if the remains are found in a different context than a clandestine grave. Analyses have been performed using petrographic microscope and scanning electron microscope microanalysis (SEM-EDS) on bones, and point out the presence of vivianite crystallizations on the bones. This evidence, thanks to the significance of vivianite in the archaeological context, can be regarded as a marker of the permanence of the human remains into the soil, like a ‘buried evidence' testimonial; on the contrary the absence of vivianite is not indicative of a ‘non buried status'. Further studies and new experiments are in progress in order to clarify the pathways of vivianite crystallization on different skeletal districts, in different

  5. Review of human osseal remains from XVI-XVIII centuries cemetery of Zatveretsky Posad (Tver, Russia

    Directory of Open Access Journals (Sweden)

    Andrei V. Zinoviev

    2010-06-01

    Full Text Available Human osseal remains from the cemetery of Zatveretsky Posad at the historical Russian city of Tver revealed the data on its population in XVI-XVIII centuries. Obtained data generally agreed with the material from other contemporaneous necropoles of the city. Domination of male burials and underrepresentation of younger individuals are accompanied by the signs of poor oral hygiene. Caries has not only often destroyed majority of molars in males and females by the age of 45-50 years, but affected teeth of teenagers and even younger individuals. The heavily developed dental calculus is one of the signs of insufficient oral hygiene in adults. Possible kinship between buried is manifested by similar genetically determined cranial anomalies.

  6. An Update on the Hazards and Risks of Forensic Anthropology, Part I: Human Remains.

    Science.gov (United States)

    Roberts, Lindsey G; Dabbs, Gretchen R; Spencer, Jessica R

    2016-01-01

    This work reviews the hazards and risks of practicing forensic anthropology in North America, with a focus on pathogens encountered through contact with unpreserved human remains. Since the publication of Galloway and Snodgrass' seminal paper concerning the hazards of forensic anthropology, research has provided new information about known pathogen hazards, and regulating authorities have updated recommendations for the recognition and treatment of several infections. Additionally, forensic anthropology has gained popularity, exposing an increased number of students and practitioners to these hazards. Current data suggest many occupational exposures to blood or body fluids go unreported, especially among students, highlighting the need for this discussion. For each pathogen and associated disease, this work addresses important history, reviews routes of exposure, provides an overview of symptoms and treatments, lists decontamination procedures, and presents data on postmortem viability. Personal protection and laboratory guidelines should be established and enforced in conjunction with the consideration of these data. © 2015 American Academy of Forensic Sciences.

  7. Cerebral water and ion balance remains stable when humans are exposed to acute hypoxic exercise

    DEFF Research Database (Denmark)

    Avnstorp, Magnus B; Rasmussen, Peter; Brassard, Patrice

    2015-01-01

    both circumstances. No cerebral net exchange of Na(+) or K(+) was evident. Likewise, no significant net-exchange of water over the brain was demonstrated and the arterial and jugular venous hemoglobin concentrations were similar. CONCLUSION: Challenging exercise in hypoxia for 30 min affected muscle......Avnstorp, Magnus B., Peter Rasmussen, Patrice Brassard, Thomas Seifert, Morten Overgaard, Peter Krustrup, Niels H. Secher, and Nikolai B. Nordsborg. Cerebral water and ion balance remains stable when humans are exposed to acute hypoxic exercise. High Alt Med Biol 16:000-000, 2015.-Background...... intense exercise is carried out in hypoxia and monitored the influence of muscle metabolism for changes in arterial variables. METHODS: On two separate days, in random order, 30 min cycling exercise was performed in either hypoxia (10% O2) or normoxia at an intensity that was exhaustive in the hypoxic...

  8. First record of Talaromyces udagawae in soil related to decomposing human remains in Argentina.

    Science.gov (United States)

    Tranchida, María C; Centeno, Néstor D; Stenglein, Sebastián A; Cabello, Marta N

    2016-01-01

    The morphologic features of Talaromyces udagawae Stolk and Samson are here described and illustrated. This teleomorphic Ascomycota fungus was isolated from soil obtained in Buenos Aires province (Argentina) from beneath a human cadaver in an advanced state of decomposition. After washing and serial dilution of the soil along with moist-chamber techniques for fungal cultivation, T. udagawae formed very restricted colonies of bright yellow color on different growth media with 8-ascospored asci. The ascospores were ellipsoidal and ornamented. The anamorphic state was not observed. Molecular-genetic techniques identified the species. The present record is the first of the species in Argentina, pointing it as a tool to identify soils where cadaver decomposition occurs. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Dental erosion in archaeological human remains: A critical review of literature and proposal of a differential diagnosis protocol.

    Science.gov (United States)

    Coupal, Isabelle; Sołtysiak, Arkadiusz

    2017-12-01

    Although studies of dental wear on archaeological human remains have largely focused on mechanical wear (attrition and abrasion) in the past, chemical wear (erosion) is being increasingly identified as a separate form of wear. This paper aims to review the current state of research and to develop a protocol that may be universally used by biorchaeologists to specifically identify dental erosion. A critical review of literature has been done in order to highlight the issues related to diagnosis of dental erosion in archaeological human remains. The bodies of work based on the analysis of both modern and archaeological dentitions raise their separate problems. In addition to a need to re-evaluate symptoms of dental erosion, notably dentin 'cupping', it is apparent that no specific protocol is adapted from medical to archaeological sciences. Authors rather rely on tooth wear indices and photographs of modern clinical cases for diagnosis. Furthermore, the diagenetic chemical alternation has rarely been considered as a bias. Here we suggest a three-step protocol: the primary method is the microscopic identification of dental erosion by SEM, followed by the exclusion of taphonomic aetiology on surrounding bone and soil pH analysis. Archaeologists should also explore possible causative agents of wear using archaeological and historic knowledge about the population being analyzed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. DNA Identification of Commingled Human Remains from the Cemetery Relocated by Flooding in Central Bosnia and Herzegovina.

    Science.gov (United States)

    Čakar, Jasmina; Pilav, Amela; Džehverović, Mirela; Ahatović, Anesa; Haverić, Sanin; Ramić, Jasmin; Marjanović, Damir

    2018-01-01

    The floods in Bosnia and Herzegovina in May 2014 caused landslides all over the country. In the small village of Šerići, near the town of Zenica, a landslide destroyed the local cemetery, relocated graves, and commingled skeletal remains. As the use of other physical methods of identification (facial recognition, fingerprint analysis, dental analysis, etc.) was not possible, DNA analysis was applied. DNA was isolated from 20 skeletal remains (bone and tooth samples) and six reference samples (blood from living relatives) and amplified using PowerPlex ® Fusion and PowerPlex ® Y23 kits. DNA profiles were generated for all reference samples and 17 skeletal remains. A statistical analysis (calculation of paternity, maternity, and sibling indexes and matching probabilities) resulted in 10 positive identifications. In this study, 5 individuals were identified based on one reference sample. This has once again demonstrated the significance of DNA analysis in resolving the most complicated cases, such as the identification of commingled human skeletal remains. © 2017 American Academy of Forensic Sciences.

  11. Metabolites of cannabidiol identified in human urine.

    Science.gov (United States)

    Harvey, D J; Mechoulam, R

    1990-03-01

    1. Urine from a dystonic patient treated with cannabidiol (CBD) was examined by g.l.c.-mass spectrometry for CBD metabolites. Metabolites were identified as their trimethylsilyl (TMS), [2H9]TMS, and methyl ester/TMS derivatives and as the TMS derivatives of the product of lithium aluminium deuteride reduction. 2. Thirty-three metabolites were identified in addition to unmetabolized CBD, and a further four metabolites were partially characterized. 3. The major metabolic route was hydroxylation and oxidation at C-7 followed by further hydroxylation in the pentyl and propenyl groups to give 1"-, 2"-, 3"-, 4"- and 10-hydroxy derivatives of CBD-7-oic acid. Other metabolites, mainly acids, were formed by beta-oxidation and related biotransformations from the pentyl side-chain and these were also hydroxylated at C-6 or C-7. The major oxidized metabolite was CBD-7-oic acid containing a hydroxyethyl side-chain. 4. Two 8,9-dihydroxy compounds, presumably derived from the corresponding epoxide were identified. 5. Also present were several cyclized cannabinoids including delta-6- and delta-1-tetrahydrocannabinol and cannabinol. 6. This is the first metabolic study of CBD in humans; most observed metabolic routes were typical of those found for CBD and related cannabinoids in other species.

  12. Ancient genomics in India: Clarifying the maternal origins of 160-year-old human remains

    Directory of Open Access Journals (Sweden)

    Esha Bandyopadhyay

    2017-10-01

    Full Text Available Sequencing DNA from archaeological remains has opened up new possibilities for furthering our understanding of the origins and evolutionary history of modern humans [1]. However, most ancient DNA (aDNA studies, thus far, have focused on ancient samples obtained from permafrozen and temperate regions, where preservation conditions are better suited for long-term DNA survival. Consequently, this has left a void in aDNA research in tropical regions such as South Asia. The primary aims of the present study were to (a test the feasibility of extracting DNA from historical samples (~160 years old from northern India, and (b correlate obtained mitochondrial DNA (mtDNA signatures with geographical origins of the individuals, as reported in historical records. A total of 30 molars were subjected to DNA extractions and Illumina indexed library preparation. All laboratory work was performed following strict aDNA standards in the clean laboratory at the Centre for Cellular and Molecular Biology, Hyderabad. Complete mtDNA genomes were targeted from all 30 samples following the DNA hybridization method outlined in Maricic et al., 2010 [2]. Captured libraries were sequenced on the Illumina HiSeq 2500 platform (100 bp paired-end mode at MedGenome Inc., Bangalore. Obtained sequences were trimmed for residual adapters using AdapterRemoval and mapped to the revised Cambridge Reference Sequence (rCRS using BWA. HaploGrep2 [3] was used to assign mtDNA haplogroups to each sample. We successfully obtained endogenous mtDNA sequences from all 30 samples, as confirmed by typical aDNA damage (cytosine deamination on the ends of DNA molecules. Coverage and depth of sequencing were in the range of 91-99.5% and 6X-371X, respectively. To ascertain the maternal origins of the individuals, mtDNA haplogroups of our samples were compared to a database compiled from published mtDNA sequences from modern South Asian individuals. Based on this, we were able to confirm northern

  13. Physical activity according to sex in the argar culture. An approach based on the human remains

    Directory of Open Access Journals (Sweden)

    Jiménez-Brobeil, Silvia A.

    2004-12-01

    Full Text Available A collection of human remains, from the Argaric Culture sites, was studied to broaden knowledge about the physical activity carried out by those populations. Three types of activity markers were analyzed: osteoarthritis, musculoskeletal stress markers and traumatisms. The obtained results coincide with the environment and terrain in which the archaeological sites were found, demonstrating a remarkable difference between sexes. Although it is impossible to determine the profession of the studied individuals, it can be affirmed that the men would perform activities that required muscular strength, walking through rugged and steeped terrain in which they risked suffering further trauma. The women, however, carried out activities centred around the domestic environment.

    Se estudian restos humanos procedentes de yacimientos de la Cultura de El Argar con el objetivo de ampliar el conocimiento sobre la actividad física llevada a cabo por los individuos. Se analizan tres tipos de marcadores: la artrosis, los marcadores de estrés músculo-esquelético y los traumatismos. Los resultados obtenidos son coincidentes con el entorno y los terrenos en los que se ubicaron los asentamientos argáricos y señalan una clara diferencia entre sexos. Aunque es imposible determinar la “profesión” de los individuos, sí se puede afirmar que los varones realizarían actividades que requerían fuerza muscular, caminar por terrenos duros y escarpados y en las que había riesgo de sufrir traumatismos. Las mujeres, sin embargo, llevarían a cabo actividades centradas en el entorno doméstico.

  14. Identifying barriers to remaining physically active after rehabilitation: differences in perception between physical therapists and older adult patients.

    Science.gov (United States)

    Zalewski, Kathryn; Alt, Carlynn; Arvinen-Barrow, Monna

    2014-06-01

    Cross-sectional study. To describe readiness for change and barriers to physical activity in older adults and to contrast perceptions of physical therapists and patients using the Barriers to Being Active Quiz. Regular physical activity is vital to recovery after discharge from physical therapy. Physical therapists are positioned to support change in physical activity habits for those transitioning to home care. Understanding of readiness for change and barriers to physical activity could optimize recovery. Thirteen physical therapists enrolled in the study and invited patients who met the inclusion criteria to enroll (79 patients enrolled). The physical therapists provided the ICD-9 code, the physical therapist diagnosis, and completed the Barriers to Being Active Quiz as they perceived their patients would. The enrolled patients provided demographics and filled out the Satisfaction With Life Scale, the stages-of-change scale for physical activity, and the Barriers to Being Active Quiz. Patients were predominantly in the early stages of readiness for change. Both patients and physical therapists identified lack of willpower as the primary barrier to physical activity. Patients identified lack of willpower and social influence as critical barriers more often than physical therapists, whereas physical therapists identified fear of injury and lack of time more often than their patients did. Differences between physical therapists and their patients were noted for fear of injury (z = 2.66, P = .008) and lack of time (z = 3.46, P = .001). The stage of change for physical activity impacted perception of social influence (χ2 = 9.64, Pbarriers to physical activity may allow physical therapists to better tailor intervention strategies to impact physical activity behavior change.

  15. Biomolecular identification of ancient Mycobacterium tuberculosis complex DNA in human remains from Britain and continental Europe.

    Science.gov (United States)

    Müller, Romy; Roberts, Charlotte A; Brown, Terence A

    2014-02-01

    Tuberculosis is known to have afflicted humans throughout history and re-emerged towards the end of the 20th century, to an extent that it was declared a global emergency in 1993. The aim of this study was to apply a rigorous analytical regime to the detection of Mycobacterium tuberculosis complex (MTBC) DNA in 77 bone and tooth samples from 70 individuals from Britain and continental Europe, spanning the 1st-19th centuries AD. We performed the work in dedicated ancient DNA facilities designed to prevent all types of modern contamination, we checked the authenticity of all products obtained by the polymerase chain reaction, and we based our conclusions on up to four replicate experiments for each sample, some carried out in an independent laboratory. We identified 12 samples that, according to our strict criteria, gave definite evidence for the presence of MTBC DNA, and another 22 that we classified as "probable" or "possible." None of the definite samples came from vertebrae displaying lesions associated with TB. Instead, eight were from ribs displaying visceral new bone formation, one was a tooth from a skeleton with rib lesions, one was taken from a skeleton with endocranial lesions, one from an individual with lesions to the sacrum and sacroiliac joint and the last was from an individual with no lesions indicative of TB or possible TB. Our results add to information on the past temporal and geographical distribution of TB and affirm the suitability of ribs for studying ancient TB. Copyright © 2013 Wiley Periodicals, Inc.

  16. Cells in human postmortem brain tissue slices remain alive for several weeks in culture

    NARCIS (Netherlands)

    Verwer, Ronald W. H.; Hermens, Wim T. J. M. C.; Dijkhuizen, PaulaA; ter Brake, Olivier; Baker, Robert E.; Salehi, Ahmad; Sluiter, Arja A.; Kok, Marloes J. M.; Muller, Linda J.; Verhaagen, Joost; Swaab, Dick F.

    2002-01-01

    Animal models for human neurological and psychiatric diseases only partially mimic the underlying pathogenic processes. Therefore, we investigated the potential use of cultured postmortem brain tissue from adult neurological patients and controls. The present study shows that human brain tissue

  17. New records of forensic entomofauna in legally buried and exhumed human infants remains in Buenos Aires, Argentina.

    Science.gov (United States)

    Mariani, Roxana; García-Mancuso, Rocío; Varela, Graciela L; Kierbel, Ivana

    2017-11-01

    The study of carrion fauna associated with buried human corpses from a forensic perspective could provide useful information in criminal investigations. Insects and other arthropods remains sampled of 44 legally exhumed infant skeletons from La Plata (Buenos Aires, Argentina). They were identified at different taxonomic levels depending on the state of preservation. The specific diversity, abundance and frequency were analyzed and each taxon was assigned to the hypothetical colonization sequence: burial colonization, post-exhumation contamination at cemetery deposit or soil fauna. The phorid Dohrniphora sp. is mentioned for the first time in Argentina as carrion fauna of underground colonization, and the assemblage of Dohrniphora sp., Megaselia scalaris and Hydrotaea aenescens is proposed as indicator of buried cadavers. These findings provide new useful data to be applied in forensic entomology research. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  18. Below the Callus Surface: Applying Paleohistological Techniques to Understand the Biology of Bone Healing in Skeletonized Human Remains.

    Science.gov (United States)

    Assis, Sandra; Keenleyside, Anne

    2016-01-01

    Bone trauma is a common occurrence in human skeletal remains. Macroscopic and imaging scrutiny is the approach most currently used to analyze and describe trauma. Nevertheless, this line of inquiry may not be sufficient to accurately identify the type of traumatic lesion and the associated degree of bone healing. To test the usefulness of histology in the examination of bone healing biology, we used an integrative approach that combines gross inspection and microscopy. Six bone samples belonging to 5 adult individuals with signs of bone trauma were collected from the Human Identified Skeletal Collection from the Museu Bocage (Lisbon, Portugal). Previous to sampling, the lesions were described according to their location, morphology, and healing status. After sampling, the bone specimens were prepared for plane light and polarized light analysis. The histological analysis was pivotal: (1) to differentiate between types of traumatic lesions; (2) to ascertain the posttraumatic interval, and (3) to diagnose other associated pathological conditions. The outer surface of a bone lesion may not give a complete picture of the biology of the tissue's response. Accordingly, microscopic analysis is essential to differentiate, characterize, and classify trauma signs. © 2016 S. Karger AG, Basel.

  19. The characterization of Helicobacter pylori DNA associated with ancient human remains recovered from a Canadian glacier.

    Directory of Open Access Journals (Sweden)

    Treena Swanston

    2011-02-01

    Full Text Available Helicobacter pylori is a gram-negative bacterium that colonizes the stomach of nearly half of the world's population. Genotypic characterization of H. pylori strains involves the analysis of virulence-associated genes, such as vacA, which has multiple alleles. Previous phylogenetic analyses have revealed a connection between modern H. pylori strains and the movement of ancient human populations. In this study, H. pylori DNA was amplified from the stomach tissue of the Kwäday Dän Ts'ìnchi individual. This ancient individual was recovered from the Samuel Glacier in Tatshenshini-Alsek Park, British Columbia, Canada on the traditional territory of the Champagne and Aishihik First Nations and radiocarbon dated to a timeframe of approximately AD 1670 to 1850. This is the first ancient H. pylori strain to be characterized with vacA sequence data. The Tatshenshini H. pylori strain has a potential hybrid vacA m2a/m1d middle (m region allele and a vacA s2 signal (s region allele. A vacA s2 allele is more commonly identified with Western strains, and this suggests that European strains were present in northwestern Canada during the ancient individual's time. Phylogenetic analysis indicated that the vacA m1d region of the ancient strain clusters with previously published novel Native American strains that are closely related to Asian strains. This indicates a past connection between the Kwäday Dän Ts'ìnchi individual and the ancestors who arrived in the New World thousands of years ago.

  20. Report: EPA Prepared to Implement Strategic Human Capital Management Activities But Challenges Remain

    Science.gov (United States)

    Report #2004-P-00024, September 20, 2004. EPA’s headquarters and regional offices are prepared to implement strategic human capital management activities, but an alignment of office-level activities to the Agency’s Strategy for Human Capital is lacking.

  1. Low calorie sweeteners: Evidence remains lacking for effects on human gut function.

    Science.gov (United States)

    Bryant, Charlotte; Mclaughlin, John

    2016-10-01

    The importance of nutrient induced gut-brain signalling in the regulation of human food intake has become an increasing focus of research. Much of the caloric excess consumed comes from dietary sugars, but our knowledge about the mechanisms mediating the physiological and appetitive effects of sweet tastants in the human gut and gut-brain axis is far from complete. The comparative effects of natural sugars vs low calorie sweeteners are also poorly understood. Research in animal and cellular models has suggested a key functional role in gut endocrine cells for the sweet taste receptors previously well described in oral taste. However human studies to date have very consistently failed to show that activation of the sweet taste receptor by low calorie sweeteners placed in the human gut fails to replicate any of the effects on gastric motility, gut hormones or appetitive responses evoked by caloric sugars. Copyright © 2016. Published by Elsevier Inc.

  2. 76 FR 58037 - Notice of Inventory Completion for Native American Human Remains and Associated Funerary Objects...

    Science.gov (United States)

    2011-09-19

    ... Mexico; and Pueblo of Zia, New Mexico. History and Description of the Remains Upon preparation for... Historical Society (History Colorado), Denver, CO; Correction AGENCY: National Park Service, Interior. ACTION...-10909, February 20, 2001). The Colorado Historical Society (History Colorado) completed an inventory of...

  3. Assessing various Infrared (IR) microscopic imaging techniques for post-mortem interval evaluation of human skeletal remains

    Science.gov (United States)

    Roider, Clemens; Ritsch-Marte, Monika; Pemberger, Nadin; Cemper-Kiesslich, Jan; Hatzer-Grubwieser, Petra; Parson, Walther; Pallua, Johannes Dominikus

    2017-01-01

    Due to the influence of many environmental processes, a precise determination of the post-mortem interval (PMI) of skeletal remains is known to be very complicated. Although methods for the investigation of the PMI exist, there still remains much room for improvement. In this study the applicability of infrared (IR) microscopic imaging techniques such as reflection-, ATR- and Raman- microscopic imaging for the estimation of the PMI of human skeletal remains was tested. PMI specific features were identified and visualized by overlaying IR imaging data with morphological tissue structures obtained using light microscopy to differentiate between forensic and archaeological bone samples. ATR and reflection spectra revealed that a more prominent peak at 1042 cm-1 (an indicator for bone mineralization) was observable in archeological bone material when compared with forensic samples. Moreover, in the case of the archaeological bone material, a reduction in the levels of phospholipids, proteins, nucleic acid sugars, complex carbohydrates as well as amorphous or fully hydrated sugars was detectable at (reciprocal wavelengths/energies) between 3000 cm-1 to 2800 cm-1. Raman spectra illustrated a similar picture with less ν2PO43−at 450 cm-1 and ν4PO43− from 590 cm-1 to 584 cm-1, amide III at 1272 cm-1 and protein CH2 deformation at 1446 cm-1 in archeological bone material/samples/sources. A semi-quantitative determination of various distributions of biomolecules by chemi-maps of reflection- and ATR- methods revealed that there were less carbohydrates and complex carbohydrates as well as amorphous or fully hydrated sugars in archaeological samples compared with forensic bone samples. Raman- microscopic imaging data showed a reduction in B-type carbonate and protein α-helices after a PMI of 3 years. The calculated mineral content ratio and the organic to mineral ratio displayed that the mineral content ratio increases, while the organic to mineral ratio decreases with

  4. Assessing various Infrared (IR microscopic imaging techniques for post-mortem interval evaluation of human skeletal remains.

    Directory of Open Access Journals (Sweden)

    Claudia Woess

    Full Text Available Due to the influence of many environmental processes, a precise determination of the post-mortem interval (PMI of skeletal remains is known to be very complicated. Although methods for the investigation of the PMI exist, there still remains much room for improvement. In this study the applicability of infrared (IR microscopic imaging techniques such as reflection-, ATR- and Raman- microscopic imaging for the estimation of the PMI of human skeletal remains was tested. PMI specific features were identified and visualized by overlaying IR imaging data with morphological tissue structures obtained using light microscopy to differentiate between forensic and archaeological bone samples. ATR and reflection spectra revealed that a more prominent peak at 1042 cm-1 (an indicator for bone mineralization was observable in archeological bone material when compared with forensic samples. Moreover, in the case of the archaeological bone material, a reduction in the levels of phospholipids, proteins, nucleic acid sugars, complex carbohydrates as well as amorphous or fully hydrated sugars was detectable at (reciprocal wavelengths/energies between 3000 cm-1 to 2800 cm-1. Raman spectra illustrated a similar picture with less ν2PO43-at 450 cm-1 and ν4PO43- from 590 cm-1 to 584 cm-1, amide III at 1272 cm-1 and protein CH2 deformation at 1446 cm-1 in archeological bone material/samples/sources. A semi-quantitative determination of various distributions of biomolecules by chemi-maps of reflection- and ATR- methods revealed that there were less carbohydrates and complex carbohydrates as well as amorphous or fully hydrated sugars in archaeological samples compared with forensic bone samples. Raman- microscopic imaging data showed a reduction in B-type carbonate and protein α-helices after a PMI of 3 years. The calculated mineral content ratio and the organic to mineral ratio displayed that the mineral content ratio increases, while the organic to mineral ratio

  5. Assessing various Infrared (IR) microscopic imaging techniques for post-mortem interval evaluation of human skeletal remains.

    Science.gov (United States)

    Woess, Claudia; Unterberger, Seraphin Hubert; Roider, Clemens; Ritsch-Marte, Monika; Pemberger, Nadin; Cemper-Kiesslich, Jan; Hatzer-Grubwieser, Petra; Parson, Walther; Pallua, Johannes Dominikus

    2017-01-01

    Due to the influence of many environmental processes, a precise determination of the post-mortem interval (PMI) of skeletal remains is known to be very complicated. Although methods for the investigation of the PMI exist, there still remains much room for improvement. In this study the applicability of infrared (IR) microscopic imaging techniques such as reflection-, ATR- and Raman- microscopic imaging for the estimation of the PMI of human skeletal remains was tested. PMI specific features were identified and visualized by overlaying IR imaging data with morphological tissue structures obtained using light microscopy to differentiate between forensic and archaeological bone samples. ATR and reflection spectra revealed that a more prominent peak at 1042 cm-1 (an indicator for bone mineralization) was observable in archeological bone material when compared with forensic samples. Moreover, in the case of the archaeological bone material, a reduction in the levels of phospholipids, proteins, nucleic acid sugars, complex carbohydrates as well as amorphous or fully hydrated sugars was detectable at (reciprocal wavelengths/energies) between 3000 cm-1 to 2800 cm-1. Raman spectra illustrated a similar picture with less ν2PO43-at 450 cm-1 and ν4PO43- from 590 cm-1 to 584 cm-1, amide III at 1272 cm-1 and protein CH2 deformation at 1446 cm-1 in archeological bone material/samples/sources. A semi-quantitative determination of various distributions of biomolecules by chemi-maps of reflection- and ATR- methods revealed that there were less carbohydrates and complex carbohydrates as well as amorphous or fully hydrated sugars in archaeological samples compared with forensic bone samples. Raman- microscopic imaging data showed a reduction in B-type carbonate and protein α-helices after a PMI of 3 years. The calculated mineral content ratio and the organic to mineral ratio displayed that the mineral content ratio increases, while the organic to mineral ratio decreases with time

  6. Bona fide colour: DNA prediction of human eye and hair colour from ancient and contemporary skeletal remains

    NARCIS (Netherlands)

    J. Draus-Barini (Jolanta); S. Walsh (Susan); E. Pośpiech (Ewelina); T. Kupiec (Tomasz); H. Głab (Henryk); W. Branicki (Wojciech); M.H. Kayser (Manfred)

    2013-01-01

    textabstractBackground: DNA analysis of ancient skeletal remains is invaluable in evolutionary biology for exploring the history of species, including humans. Contemporary human bones and teeth, however, are relevant in forensic DNA analyses that deal with the identification of perpetrators, missing

  7. Measuring human remains in the field: Grid technique, total station, or MicroScribe?

    Czech Academy of Sciences Publication Activity Database

    Sládek, Vladimír; Galeta, P.; Sosna, D.

    2012-01-01

    Roč. 221, 1-3 (2012), s. 16-22 ISSN 0379-0738 Institutional support: RVO:68081766 Keywords : Excavation * Field anthropology * Human skeleton * Measuring error Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 2.307, year: 2012

  8. Semen quality remains stable during 96 weeks of untreated human immunodeficiency virus-1 infection

    NARCIS (Netherlands)

    van Leeuwen, Elisabeth; Wit, Ferdinand W.; Prins, Jan M.; Reiss, Peter; van der Veen, Fulco; Repping, Sjoerd

    2008-01-01

    OBJECTIVE: To evaluate semen parameters during the natural course of asymptomatic human immunodeficiency virus-1 (HIV-1) infection. DESIGN: A longitudinal cohort study. SETTING: HIV outpatient clinic of the Academic Medical Center in Amsterdam, the Netherlands. PATIENT(S): 55 men infected with

  9. Not in wilderness: African vulture strongholds remain in areas with high human density

    Science.gov (United States)

    Granadeiro, José Pedro; Monteiro, Hamilton; Nuno, Ana; Lecoq, Miguel; Cardoso, Paulo; Regalla, Aissa; Catry, Paulo

    2018-01-01

    Vultures constitute an important functional group in many ecosystems, providing crucial ecosystem services both in natural and humanized environments. These scavengers are facing massive declines worldwide, but in several African countries virtually nothing is known on populations’ status and threats, hampering the development of adequate conservation strategies. In Guinea-Bissau, globally important populations of Hooded Necrosyrtes monachus and African white-backed vultures Gyps africanus were recently reported. Using the country as a study area, we aim to characterize human-vulture interactions in West Africa applying a multidisciplinary approach. We assessed the status and distribution of vulture populations using data from 1711 km of roadside transects, examined predictors of their distribution, and produced a nationwide population estimate for the Hooded Vulture, using an innovative method based on the relationship between the size of human population in settlements and vulture numbers. We conducted 47 stakeholder interviews to assess perceived roles played by vultures, and to investigate potential anthropogenic threats. Hooded vultures were strongly associated with high human population densities, whereas no relation was found between African white-backed and Rüppell’s vultures and any of the tested predictors, which included cattle density, precipitation and Normalized Difference Vegetation Index, among others. We estimate a national population of 43347 Hooded vultures, the largest population reported in the species range. Respondents were generally aware of the services provided by vultures, especially waste and carcass removal, including in urban areas. Hunting for witchcraft and traditional medicine was the most frequently recognised threat, while poisoning was ranked as having the highest impact. We hypothesise that poisoning-related mortality may be affecting African white-backed and Rüppell’s vultures’ distribution and explain their scarcity

  10. Effects of hydrated lime and quicklime on the decay of buried human remains using pig cadavers as human body analogues.

    Science.gov (United States)

    Schotsmans, Eline M J; Denton, John; Dekeirsschieter, Jessica; Ivaneanu, Tatiana; Leentjes, Sarah; Janaway, Rob C; Wilson, Andrew S

    2012-04-10

    Recent casework in Belgium involving the search for human remains buried with lime, demonstrated the need for more detailed understanding of the effect of different types of lime on cadaver decomposition and its micro-environment. Six pigs (Sus scrofa) were used as body analogues in field experiments. They were buried without lime, with hydrated lime (Ca(OH)(2)) and with quicklime (CaO) in shallow graves in sandy loam soil in Belgium and recovered after 6 months of burial. Observations from these field recoveries informed additional laboratory experiments that were undertaken at the University of Bradford, UK. The combined results of these studies demonstrate that despite conflicting evidence in the literature, hydrated lime and quicklime both delay the decay of the carcass during the first 6 months. This study has implications for the investigation of clandestine burials and for a better understanding of archaeological plaster burials. Knowledge of the effects of lime on decomposition processes also has bearing on practices involving burial of animal carcasses and potentially the management of mass graves and mass disasters by humanitarian organisations and DVI teams. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  11. Guidance on the Use of Historic Human Remains Detection Dogs for Locating Unmarked Cemeteries

    Science.gov (United States)

    2015-12-01

    needed to trigger a higher- quality alert. Therefore, the handler’s experience with their dog and their ability to communicate effectively with the... dogs are trained to locate graves where decomposition had once occurred or where human bones are scattered on the surface. Person- al communications ...the dog team surveys, the alerts result from a series of communications be- tween the dog and the handler. Each dog has their own way of working the

  12. Investigations on human and animal remains from a medieval shaft well in Ayasuluk/Ephesos (Turkey).

    Science.gov (United States)

    Kanz, Fabian; Pfeiffer-Taş, Şule; Forstenpointner, Gerhard; Galik, Alfred; Weissengruber, Gerald; Grossschmidt, Karl; Risser, Daniele U

    2014-01-01

    In course of the archaeological survey of Ayasuluk/Ephesos region (Turkey), a shaft well situated at the area of an extensive medieval bathing complex was excavated. In the stratum corresponding to the reign Mehmed II the well-preserved skeletons of two humans, an equine and a canine were recovered. Anthropological analysis of the human skeletons indentified two males aged 22 (± 3) and 36 (± 5) years. The skeleton of the younger individual showed signs of various antemortal conditions, including a well-healed fraction of right arc of the fifth lumbar vertebra, and a marked asymmetry of the shoulder joints. The older individual exhibited significant peri/postmortem injuries at the elbows, with evident signs of peeling and external burning. Also, the few elements of the cranium recovered showed also indications of burning. Archaeozoological characterization of the complete skeletons of the equine and canine established evidence of well cared-for animals of high value. The time of disposal of this group coincides with uprising of the formerly ruling Aydnoullar clan against the Ottomans in power. The human individuals recovered from the well may have been members of Aydnoullar tribe or men in service of the latter, suffering severe torture and/or mutilation for siding with the rebels after defeat.

  13. The initial changes of fat deposits during the decomposition of human and pig remains.

    Science.gov (United States)

    Notter, Stephanie J; Stuart, Barbara H; Rowe, Rebecca; Langlois, Neil

    2009-01-01

    The early stages of adipocere formation in both pig and human adipose tissue in aqueous environments have been investigated. The aims were to determine the short-term changes occurring to fat deposits during decomposition and to ascertain the suitability of pigs as models for human decomposition. Subcutaneous adipose tissue from both species after immersion in distilled water for up to six months was compared using Fourier transform infrared spectroscopy, gas chromatography-mass spectrometry and inductively coupled plasma-mass spectrometry. Changes associated with decomposition were observed, but no adipocere was formed during the initial month of decomposition for either tissue type. Early-stage adipocere formation in pig samples during later months was detected. The variable time courses for adipose tissue decomposition were attributed to differences in the distribution of total fatty acids between species. Variations in the amount of sodium, potassium, calcium, and magnesium were also detected between species. The study shows that differences in total fatty acid composition between species need to be considered when interpreting results from experimental decomposition studies using pigs as human body analogs.

  14. Brief communication: a proposed osteological method for the estimation of pubertal stage in human skeletal remains.

    Science.gov (United States)

    Shapland, Fiona; Lewis, Mary E

    2013-06-01

    Puberty forms an important threshold between childhood and adulthood, but this subject has received little attention in bioarchaeology. The new application of clinical methods to assess pubertal stage in adolescent skeletal remains is explored, concentrating on the development of the mandibular canine, hamate, hand phalanges, iliac crest and distal radius. Initial results from the medieval cemetery of St. Peter's Church, Barton-upon-Humber, England suggest that application of these methods may provide insights into aspects of adolescent development. This analysis indicates that adolescents from this medieval site were entering the pubertal growth spurt at a similar age to their modern counterparts, but that the later stages of pubertal maturation were being significantly delayed, perhaps due to environmental stress. Continued testing and refinement of these methods on living adolescents is still necessary to improve our understanding of their significance and accuracy in predicting pubertal stages. Copyright © 2013 Wiley Periodicals, Inc.

  15. Bioarchaeological Analysis of the Human Skeletal Remains from the Late Mediaeval Cemetery of Koprivno, Southern Croatia

    Directory of Open Access Journals (Sweden)

    Mario Novak

    2011-06-01

    Full Text Available The paper presents the results of bioarchaeological analysis of the late mediaeval (13th-14th century skeletal sample from Koprivno, southern Croatia. Skeletal remains of 21 individuals (eight males, nine females, and four subadults were examined for the possible presence of dental pathologies (caries and alveolar bone diseases, subadult stress indicators (cribra orbitalia and dental enamel hypoplasia, degenerative osteoarthritis of the vertebrae and major joints, Schmorl’s nodes on vertebrae, periostitis, and bone trauma. The analysed sample is characterised by high frequency of alveolar bone disease, most probably as a result of somewhat longer average life span (around 41 years and very poor oral hygiene, while the data concerning dental caries indicate mixed diet evenly based on meat and cereals. High frequencies of cribra orbitalia, dental enamel hypoplasia and periostitis suggest frequent episodes of physiological stress (hunger, epidemics of infectious diseases which is in accordance with historical data. Distribution and prevalence of cranial traumas strongly suggest a relatively high degree of interpersonal violence in the analysed community.

  16. Does the centre of mass remain stable during complex human postural equilibrium tasks in weightlessness?

    Science.gov (United States)

    Stapley, Paul; Pozzo, Thierry

    In normal gravity conditions the execution of voluntary movement involves the displacement of body segments as well as the maintenance of a stable reference value for equilibrium control. It has been suggested that centre of mass (CM) projection within the supporting base (BS) is the stabilised reference for voluntary action, and is conserved in weightlessness. The purpose of this study was to determine if the CM is stabilised during whole body reaching movements executed in weightlessness. The reaching task was conducted by two cosmonauts aboard the Russian orbital station MIR, during the Franco-Russian mission ALTAIR, 1993. Movements of reflective markers were recorded using a videocamera, successive images being reconstructed by computer every 40ms. The position of the CM, ankle joint torques and shank and thigh angles were computed for each subject pre- in- and post-flight using a 7-link mathematical model. Results showed that both cosmonauts adopted a backward leaning posture prior to reaching movements. Inflight, the CM was displaced throughout values in the horizontal axis three times those of pre-flight measures. In addition, ankle dorsi flexor torques inflight increased to values double those of pre- and post-flight tests. This study concluded that CM displacements do not remain stable during complex postural equilibrium tasks executed in weightlessness. Furthermore, in the absence of gravity, subjects changed their strategy for producing ankle torque during spaceflight from a forward to a backward leaning posture.

  17. A foetal tile from an archaeological site: anthropological investigation of human remains recovered in a medieval cemetery in Northern Italy.

    Science.gov (United States)

    Licata, Marta; Rossetti, Chiara; Tosi, Adelaide; Badino, Paola

    2018-06-01

    The recovery of foetal remains is very sporadic in archaeology, especially due the scarce degree of bone mineralisation. This paper presents the singular archaeological discovery of a foetal tile preserving the bone remains, object of our anthropological examination. The foetal tile was discovered during an archaeological excavation in a medieval site (Northern Italy). The tile was analysed by CT scan and later, human remains were anthropologically examined. The archaeological investigation revealed a special ritual destined to foetuses while forensic anthropological analysis allowed estimating the gestational age near to 21-24 weeks.

  18. Non-Metric Dental Traits in Human Skeletal Remains from Transcaucasian Populations: Phylogenetic and Diachronic Evidence

    Directory of Open Access Journals (Sweden)

    Khudaverdyan Anahit Yu.

    2014-07-01

    Full Text Available The aim of the study is the assessment of biological distance between populations from Transcaucasia on the basis of the frequency of dental morphological traits. It is well known that these traits are characterised by a high inter-population differentiation, low sexual dimorphism, and their recording is loaded by relatively small intra and inter observer error. The dental morphological traits are successfully used in the description and explanation of the microevolutionary and ethnogenetic processes. This paper presents the results of the odontological differentiation of human populations from Transcaucasia. The comparative analysis was carried out on the basis of 12 groups. From the obtained results, we can draw the following conclusions: The populations of Armenian Highland and Georgia can be differentiated as far as the frequency of dental morphological traits are concerned. They also do not exhibit similar intragroup variability. Biocultural diversity of ancient Transcaucasian populations has not been studied extensively; therefore, delineating some of the patterns of phenotypic variation may be useful for understanding their ongoing evolution.

  19. Analysis of suspected trace human remains from an indoor concrete surface.

    Science.gov (United States)

    Zimmermann, Carolyn M; Laskay, Unige A; Jackson, Glen P

    2008-11-01

    This paper describes the sequence of analyses used to determine the nature of a stain located on the floor of room in the former Athens Mental Health and Retardation Hospital in Athens, OH. The location of the stain was reported to be the position in which a decomposing body was discovered on January 11, 1979. The current stain is found to contain strong evidence for both natural decomposition products and deliberate adulteration. Microscopic analyses, solubility tests, FTIR, ICP-OES, pyrolysis-MS, and derivatization GC-MS were consistent in determining the removable parts of the stain to be composed mostly of calcium and sodium salts of free fatty acids, such as palmitic acid, consistent with previous descriptions of adipocere. The free fatty acids could have been formed via known bacterial degradation pathways or via saponification through the basic environment caused through contact with the concrete. To our knowledge, adipocere formation on an exposed indoor environment has not been described before. The stain and concrete also show signs of being chemically modified with an acidic reagent, such as Blu-Lite--a phosphoric acid-based cleaner that was a commonly used cleaner in the building from the time of discovery to the present day. The chemical etching appears to have been restricted to an area resembling the shape of a human body, which is consistent with deliberate adulteration of the appearance of the stain.

  20. 78 FR 64436 - Disposition of Unclaimed Human Remains and Other Cultural Items Discovered on Federal Lands After...

    Science.gov (United States)

    2013-10-29

    .... The oral comments were transcribed and all comments retained. Results of the comments and... that human remains and funerary objects would be subject to a common understanding of respect for the... misunderstandings when either is not well understood. Tribal representatives stated there should be no time limits...

  1. Human mobility on the Brazilian coast: an analysis of strontium isotopes in archaeological human remains from Forte Marechal Luz Sambaqui

    Directory of Open Access Journals (Sweden)

    Murilo Q. R Bastos

    2011-06-01

    Full Text Available This study investigated strontium isotopes in the dental enamel of 32 human skeletons from Forte Marechal Luz sambaqui (shellmound, Santa Catarina, Brazil, aiming at identifying local and non-local individuals. The archeological site presents pot sherds in the uppermost archeological layers. Dental enamel was also examined from specimens of terrestrial fauna (87Sr/86Sr = 0. 71046 to 0. 71273 and marine fauna (87Sr/86Sr = 0. 70917. The 87Sr/86Sr isotope ratio for individuals classified as locals ranged from 0. 70905 to 0. 71064 and was closer to the isotope ratio of the seawater than to the ratio of the terrestrial fauna, indicating a strong influence of marine strontium on the inhabitants of this sambaqui. The results indicate the existence of three non-local individuals (87Sr/86Sr = 0. 70761 to 0. 70835, buried in both the level without pottery and the layer with pottery, possibly originated from the Santa Catarina Plateau, close to the municipality of Lages, or from the Curitiba Plateau. The occurrence of a slight difference between the isotope ratios of local individuals buried in the archeological layer without pottery, when compared to those in the layer with pottery, suggests a possible change in dietary patterns between these two moments in the site's occupationO presente estudo investigou isótopos de estrôncio em esmalte dentário de 32 remanescentes humanos do sambaqui do Forte Marechal Luz, Santa Catarina, Brasil, com o objetivo de identificar indivíduos locais e não-locais. O sítio arqueológico apresenta fragmentos de cerâmica em suas camadas arqueológicas mais recentes. Além das amostras humanas, foram analisadas amostras de esmalte dentário de espécimes de fauna terrestre (87Sr/86Sr = 0,71046 a 0,71273 e fauna marinha (87Sr/86Sr = 0,70917. A razão 87Sr/86Sr dos indivíduos classificados como locais variou de 0,70905 a 0,71064, sendo próxima a razão de estrôncio existente nos oceanos e distante da razão obtida para a

  2. Role of stable isotope analyses in reconstructing past life-histories and the provenancing human skeletal remains: a review

    Directory of Open Access Journals (Sweden)

    Sehrawat Jagmahender Singh

    2017-09-01

    Full Text Available This article reviews the present scenario of use of stable isotopes (mainly δ13C, δ15N, δ18O, 87Sr to trace past life behaviours like breast feeding and weaning practices, the geographic origin, migration history, paleodiet and subsistence patterns of past populations from the chemical signatures of isotopes imprinted in human skeletal remains. This approach is based on the state that food-web isotopic signatures are seen in the human bones and teeth and such signatures can change parallely with a variety of biogeochemical processes. By measuring δ13C and δ15N isotopic values of subadult tissues of different ages, the level of breast milk ingestion at particular ages and the components of the complementary foods can be assessed. Strontium and oxygen isotopic analyses have been used for determining the geographic origins and reconstructing the way of life of past populations as these isotopes can map the isotopic outline of the area from where the person acquired water and food during initial lifetime. The isotopic values of strontium and oxygen values are considered specific to geographical areas and serve as reliable chemical signatures of migration history of past human populations (local or non-local to the site. Previous isotopic studies show that the subsistence patterns of the past human populations underwent extensive changes from nomadic to complete agricultural dependence strategies. The carbon and nitrogen isotopic values of local fauna of any archaeological site can be used to elucidate the prominence of freshwater resources in the diet of the past human populations found near the site. More extensive research covering isotopic descriptions of various prehistoric, historic and modern populations is needed to explore the role of stable isotope analysis for provenancing human skeletal remains and assessing human migration patterns/routes, geographic origins, paleodiet and subsistence practices of past populations.

  3. A Retrospective Review of Forensic Odontology Reports Written by the Joint POW/MIA Accounting Command Central Identification Laboratory for Remains Identified from the Korean War.

    Science.gov (United States)

    Shiroma, Calvin Y

    2016-01-01

    As of August 2014, the Joint POW/MIA Accounting Command has identified the remains of 1980 previously unknown U.S. service members; 280 were from the Korean War. To determine the accuracy and completeness of the available antemortem (AM) dental records, a review of the AM/postmortem (AM/PM) dental record comparisons from 233 Forensic Odontology Reports written in support of remains identified from the Korean War was performed. Seventy-two AM/PM comparisons resulted in exact dental chartings while 161 contained discrepancies which were explainable. Explainable discrepancies include undocumented treatment (103), incorrectly charted third molars as missing (82), differing opinions of specific molars present/missing (20), and erroneous treatment documentation and/or misidentification of teeth present/missing (22, other than molars). Reassessment has revealed varying levels of completeness for our available AM dental records, the need to thoroughly review our computerized comparisons, adjust our comparisons to include molar pattern variations/third molars, and updating our database comparison program. Published 2015. This article is a U.S. Government work and is in the public domain in the U.S.A.

  4. [Human remains in museums: research, preservation and communication. The experience of Turin University Museum of Anthropology and Etnography].

    Science.gov (United States)

    Boano, Rosa; Grilletto, Renato; Rabino Massa, Emma

    2013-01-01

    The creation of large scientific collections has been an important development for anthropological and paleopathological research. Indeed the biological collections are irreplaceable reference systems for the biological reconstruction of past population. They also assume the important role of anthropological archives and, in the global description of man, permit the integration of historical data with those from bio-anthropolgical research. Thinking about the role of mummies and bones as scientific resources, best practice of preservation of ancient specimens should be of high priority for institution and researchers. By way of example, the authors mention their experience regarding ancient human remains preserved in the Museum of Anthropology and Ethnography at the University of Turin.

  5. Middle pleistocene human remains from Tourville-la-Rivière (Normandy, France and their archaeological context.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Faivre

    Full Text Available Despite numerous sites of great antiquity having been excavated since the end of the 19th century, Middle Pleistocene human fossils are still extremely rare in northwestern Europe. Apart from the two partial crania from Biache-Saint-Vaast in northern France, all known human fossils from this period have been found from ten sites in either Germany or England. Here we report the discovery of three long bones from the same left upper limb discovered at the open-air site of Tourville-la-Rivière in the Seine Valley of northern France. New U-series and combined US-ESR dating on animal teeth produced an age range for the site of 183 to 236 ka. In combination with paleoecological indicators, they indicate an age toward the end of MIS 7. The human remains from Tourville-la-Rivière are attributable to the Neandertal lineage based on morphological and metric analyses. An abnormal crest on the left humerus represents a deltoid muscle enthesis. Micro- and or macro-traumas connected to repetitive movements similar to those documented for professional throwing athletes could be origin of abnormality.

  6. Palaeopathology and genes: investigating the genetics of infectious diseases in excavated human skeletal remains and mummies from past populations.

    Science.gov (United States)

    Anastasiou, Evilena; Mitchell, Piers D

    2013-10-01

    The aim of this paper is to review the use of genetics in palaeomicrobiology, and to highlight the importance of understanding past diseases. Palaeomicrobiology is the study of disease pathogens in skeletal and mummified remains from archaeological contexts. It has revolutionarised our understanding of health in the past by enabling a deeper knowledge of the origins and evolution of many diseases that have shaped us as a species. Bacterial diseases explored include tuberculosis, leprosy, bubonic plague, typhoid, syphilis, endemic and epidemic typhus, trench fever, and Helicobacter pylori. Viral diseases discussed include influenza, hepatitis B, human papilloma virus (HPV), human T-cell lymphotrophic virus (HTLV-1) and human immunodeficiency virus (HIV). Parasitic diseases investigated include malaria, leishmaniasis, Chagas' disease, roundworm, whipworm, pinworm, Chinese liver fluke, fleas and lice. Through a better understanding of disease origins and their evolution, we can place into context how many infectious diseases are changing over time, and so help us estimate how they may change in the future. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Short-term effects of hydrated lime and quicklime on the decay of human remains using pig cadavers as human body analogues: Laboratory experiments.

    Science.gov (United States)

    Schotsmans, Eline M J; Denton, John; Fletcher, Jonathan N; Janaway, Robert C; Wilson, Andrew S

    2014-05-01

    Contradictions and misconceptions regarding the effect of lime on the decay of human remains have demonstrated the need for more research into the effect of different types of lime on cadaver decomposition. This study follows previous research by the authors who have investigated the effect of lime on the decomposition of human remains in burial environments. A further three pig carcasses (Sus scrofa), used as human body analogues, were observed and monitored for 78 days without lime, with hydrated lime (Ca(OH)2) and with quicklime (CaO) in the taphonomy laboratory at the University of Bradford. The results showed that in the early stages of decay, the unlimed and hydrated lime cadavers follow a similar pattern of changes. In contrast, the application of quicklime instigated an initial acceleration of decay. Microbial investigation demonstrated that the presence of lime does not eliminate all aerobic bacteria. The experiment also suggested that lime functions as a sink, buffering the carbon dioxide evolution. This study complements the field observations. It has implications for the investigation of time since death of limed remains. Knowledge of the effects of lime on decomposition processes is of interest to forensic pathologists, archaeologists, humanitarian organisations and those concerned with disposal of animal carcasses or human remains in mass disasters. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. The Tedeschi collection: A collection of documented and undocumented human skeletal remains at the Museum of Anthropology, Padua University (Italy).

    Science.gov (United States)

    Carrara, Nicola; Scaggion, Cinzia; Holland, Emily

    2018-04-01

    Documented and undocumented skeletal collections offer unique windows into life in the past and are integral for research in biological anthropology. The objective of this article is to describe the documented and undocumented collections curated by the Museum of Anthropology at Padua University (Italy) to demonstrate their potential for research and encourage researchers to consider them for future projects. The collection was established by Prof. Enrico Tedeschi at the beginning of 20th century, and dates to the late 19th and early 20th century. The collection consists primarily of individuals excavated from cemeteries, ossarios, or unclaimed individuals donated by hospitals or other institutions. Both documented and undocumented human skeletal remains are included in the collection, totalling 1,580 individuals. Associated documented information including age at death, date of death, sex, occupation, and cause of death is available in different combinations for 293 individuals of varying completeness (188 crania only, 93 crania and postcranial, 12 postcranial only). Origin and chronological period are known for the remaining 1,287 individuals. Overall, this little studied collection could be particularly useful for researchers interested in craniometrics, dentition, and 19th and 20th century health and demography in Italy. The documented skeletons will be especially useful for forensic anthropological research. © 2018 Wiley Periodicals, Inc.

  9. Ñuagapua (Chaco, Bolivia): Evidence for the latest occurrence of megafauna in association with human remains in South America

    Science.gov (United States)

    Coltorti, Mauro; Della Fazia, Jacopo; Paredes Rios, Freddy; Tito, Giuseppe

    2012-02-01

    Quebrada (stream) Ñuagapua, which is located in the Bolivian Chaco in the Andean foothill generates an alluvial fan many kilometres in length. Three major lithostratigraphic units characterise the sedimentary sequence in this region. The lower and upper parts are formed from predominantly sandy sediments that demonstrate rapid growth of the alluvial fan, associated with an intense erosion of barren slopes. The intermediate unit consists of forest soil that seals deep channels containing bones together with a forest association. The remains of a wooden plank, dated 140 yr BP, were found at the top of this soil, which laterally contains charcoals, ash layers and large charred trunks, sometimes in growth positions. Roots localised in this layer also sustain a number of very large still living trees. These findings are evidence of a recent phase of alluvial fan sedimentation resulting from slope erosion activated by forest clearing. The Chaco has been intensively settled for agricultural and pastoral purposes since the 18th century. The lower unit contains a hearth, scattered burnt bones, flint flakes and ceramic artefacts. Radiometric dating indicates a middle Holocene human occupation, between ca. 7.79 and 6.65 ka cal yr BP. We suggest that the sedimentary unit is associated with intense soil erosion processes triggered by early Neolithic deforestation. A sandy layer of the lower unit, slightly above the archaeological remains, contains transported bones of megafaunal elements that apparently represent the South American latest occurrence of some extinct taxa. The mammal association is highly heterogeneous, containing species living in aquatic, forest, prairie and savannah environments from a very specific layer that represents the almost simultaneous burial of animals killed slightly up-valley. This anomalous association is probably the result of human impact as opening the forest favoured the introduction of open environment fauna that had previously survived on

  10. Identifying Requirements for Effective Human-Automation Teamwork

    Energy Technology Data Exchange (ETDEWEB)

    Jeffrey C. Joe; John O' Hara; Heather D. Medema; Johanna H. Oxstrand

    2014-06-01

    Previous studies have shown that poorly designed human-automation collaboration, such as poorly designed communication protocols, often leads to problems for the human operators, such as: lack of vigilance, complacency, and loss of skills. These problems often lead to suboptimal system performance. To address this situation, a considerable amount of research has been conducted to improve human-automation collaboration and to make automation function better as a “team player.” Much of this research is based on an understanding of what it means to be a good team player from the perspective of a human team. However, the research is often based on a simplified view of human teams and teamwork. In this study, we sought to better understand the capabilities and limitations of automation from the standpoint of human teams. We first examined human teams to identify the principles for effective teamwork. We next reviewed the research on integrating automation agents and human agents into mixed agent teams to identify the limitations of automation agents to conform to teamwork principles. This research resulted in insights that can lead to more effective human-automation collaboration by enabling a more realistic set of requirements to be developed based on the strengths and limitations of all agents.

  11. Human Development in Romania: A Comparative Approach to Identifying Shortcomings

    Directory of Open Access Journals (Sweden)

    Robert STEFAN

    2017-12-01

    Full Text Available Following the research carried out by the economist Mahbub ul Haq, derived from the studies of Amartya Sen on human capabilities, in 1990, the United Nations Development Programme (UNDP published its first Human Development Report. It introduced the notion that development of a country is not merely equal to economic growth, but has the ultimate purpose of enriching human life by expanding people’s choices. Thus, Human Development seeks to reveal the fundamental role of human life: that of reaching its full potential. Even after 28 years since the fall of communism, the political environment in Romania continues to be unsopportive of proper development. This study seeks to identify the shortcomings of the primary dimensions of Human Development in Romania and hopefully make a firm and rhetorical call to action.

  12. Proteogenomic Analysis Identifies a Novel Human SHANK3 Isoform

    Directory of Open Access Journals (Sweden)

    Fahad Benthani

    2015-05-01

    Full Text Available Mutations of the SHANK3 gene have been associated with autism spectrum disorder. Individuals harboring different SHANK3 mutations display considerable heterogeneity in their cognitive impairment, likely due to the high SHANK3 transcriptional diversity. In this study, we report a novel interaction between the Mutated in colorectal cancer (MCC protein and a newly identified SHANK3 protein isoform in human colon cancer cells and mouse brain tissue. Hence, our proteogenomic analysis identifies a new human long isoform of the key synaptic protein SHANK3 that was not predicted by the human reference genome. Taken together, our findings describe a potential new role for MCC in neurons, a new human SHANK3 long isoform and, importantly, highlight the use of proteomic data towards the re-annotation of GC-rich genomic regions.

  13. Long-term effects of hydrated lime and quicklime on the decay of human remains using pig cadavers as human body analogues: Field experiments.

    Science.gov (United States)

    Schotsmans, Eline M J; Fletcher, Jonathan N; Denton, John; Janaway, Robert C; Wilson, Andrew S

    2014-05-01

    An increased number of police enquiries involving human remains buried with lime have demonstrated the need for more research into the effect of different types of lime on cadaver decomposition and its micro-environment. This study follows previous studies by the authors who have investigated the effects of lime on the decay of human remains in laboratory conditions and 6 months of field experiments. Six pig carcasses (Sus scrofa), used as human body analogues, were buried without lime with hydrated lime (Ca(OH)2) and quicklime (CaO) in shallow graves in sandy-loam soil in Belgium and recovered after 17 and 42 months of burial. Analysis of the soil, lime and carcasses included entomology, pH, moisture content, microbial activity, histology and lime carbonation. The results of this study demonstrate that despite conflicting evidence in the literature, the extent of decomposition is slowed down by burial with both hydrated lime and quicklime. The more advanced the decay process, the more similar the degree of liquefaction between the limed and unlimed remains. The end result for each mode of burial will ultimately result in skeletonisation. This study has implications for the investigation of clandestine burials, for a better understanding of archaeological plaster burials and potentially for the interpretation of mass graves and management of mass disasters by humanitarian organisation and DVI teams. Copyright © 2014. Published by Elsevier Ireland Ltd.

  14. Pilot study to establish a nasal tip prediction method from unknown human skeletal remains for facial reconstruction and skull photo superimposition as applied to a Japanese male populations.

    Science.gov (United States)

    Utsuno, Hajime; Kageyama, Toru; Uchida, Keiichi; Kibayashi, Kazuhiko; Sakurada, Koichi; Uemura, Koichi

    2016-02-01

    Skull-photo superimposition is a technique used to identify the relationship between the skull and a photograph of a target person: and facial reconstruction reproduces antemortem facial features from an unknown human skull, or identifies the facial features of unknown human skeletal remains. These techniques are based on soft tissue thickness and the relationships between soft tissue and the skull, i.e., the position of the ear and external acoustic meatus, pupil and orbit, nose and nasal aperture, and lips and teeth. However, the ear and nose region are relatively difficult to identify because of their structure, as the soft tissues of these regions are lined with cartilage. We attempted to establish a more accurate method to determine the position of the nasal tip from the skull. We measured the height of the maxilla and mid-lower facial region in 55 Japanese men and generated a regression equation from the collected data. We obtained a result that was 2.0±0.99mm (mean±SD) distant from the true nasal tip, when applied to a validation set consisting of another 12 Japanese men. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  15. The human vascular endothelial cell line HUV-EC-C harbors the integrated HHV-6B genome which remains stable in long term culture.

    Science.gov (United States)

    Shioda, Setsuko; Kasai, Fumio; Ozawa, Midori; Hirayama, Noriko; Satoh, Motonobu; Kameoka, Yousuke; Watanabe, Ken; Shimizu, Norio; Tang, Huamin; Mori, Yasuko; Kohara, Arihiro

    2018-02-01

    Human herpes virus 6 (HHV-6) is a common human pathogen that is most often detected in hematopoietic cells. Although human cells harboring chromosomally integrated HHV-6 can be generated in vitro, the availability of such cell lines originating from in vivo tissues is limited. In this study, chromosomally integrated HHV-6B has been identified in a human vascular endothelial cell line, HUV-EC-C (IFO50271), derived from normal umbilical cord tissue. Sequence analysis revealed that the viral genome was similar to the HHV-6B HST strain. FISH analysis using a HHV-6 DNA probe showed one signal in each cell, detected at the distal end of the long arm of chromosome 9. This was consistent with a digital PCR assay, validating one copy of the viral DNA. Because exposure of HUV-EC-C to chemicals did not cause viral reactivation, long term cell culture of HUV-EC-C was carried out to assess the stability of viral integration. The growth rate was altered depending on passage numbers, and morphology also changed during culture. SNP microarray profiles showed some differences between low and high passages, implying that the HUV-EC-C genome had changed during culture. However, no detectable change was observed in chromosome 9, where HHV-6B integration and the viral copy number remained unchanged. Our results suggest that integrated HHV-6B is stable in HUV-EC-C despite genome instability.

  16. T-category remains an important prognostic factor for oropharyngeal carcinoma in the era of human papillomavirus.

    Science.gov (United States)

    Mackenzie, P; Pryor, D; Burmeister, E; Foote, M; Panizza, B; Burmeister, B; Porceddu, S

    2014-10-01

    To determine prognostic factors for locoregional relapse (LRR), distant relapse and all-cause death in a contemporary cohort of locoregionally advanced oropharyngeal squamous cell carcinoma (OSCC) treated with definitive chemoradiotherapy or radiotherapy alone. OSCC patients treated with definitive radiotherapy between 2005 and 2010 were identified from a prospective head and neck database. Patient age, gender, smoking history, human papillomavirus (HPV) status, T- and N-category, lowest involved nodal level and gross tumour volume of the primary (GTV-p) and nodal (GTV-n) disease were analysed in relation to LRR, distant relapse and death by way of univariate and multivariate analysis. In total, 130 patients were identified, 88 HPV positive, with a median follow-up of 42 months. On multivariate analysis HPV status was a significant predictor of LRR (hazard ratio 0.15; 95% confidence interval 0.05-0.51) and death (hazard ratio 0.29; 95% confidence interval 0.14-0.59) but not distant relapse (hazard ratio 0.53, 95% confidence interval 0.22-1.27). Increasing T-category was associated with a higher risk of LRR (hazard ratio 1.80 for T3/4 versus T1/2; 95% confidence interval 1.08-2.99), death (hazard ratio 1.37, 95% confidence interval 1.06-1.77) and distant relapse (hazard ratio 1.35; 95% confidence interval 1.00-1.83). Increasing GTV-p was associated with increased risk of distant relapse and death. N3 disease and low neck nodes were significant for LRR, distant relapse and death on univariate analysis only. Tumour HPV status was the strongest predictor of LRR and death. T-category is more predictive of distant relapse and may provide additional prognostic value for LRR and death when accounting for HPV status. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  17. Neuroendocrine cells during human prostate development: does neuroendocrine cell density remain constant during fetal as well as postnatal life?

    NARCIS (Netherlands)

    Xue, Y.; van der Laak, J.; Smedts, F.; Schoots, C.; Verhofstad, A.; de la Rosette, J.; Schalken, J.

    2000-01-01

    Knowledge concerning differentiation of neuroendocrine (NE) cells during development of the human prostate is rather fragmentary. Using immunohistochemistry combined with a morphometric method, we investigated the distribution and density of NE cells in the developing human prostate, with special

  18. Human strongyloidiasis: identifying knowledge gaps, with emphasis on environmental control

    Directory of Open Access Journals (Sweden)

    Taylor MJ

    2014-08-01

    Full Text Available Michael J Taylor, Tara A Garrard, Francis J O'Donahoo, Kirstin E Ross Health and Environment, School of the Environment, Flinders University, Adelaide, SA, Australia Abstract: Strongyloides is a human parasitic nematode that is poorly understood outside a clinical context. This article identifies gaps within the literature, with particular emphasis on gaps that are hindering environmental control of Strongyloides. The prevalence and distribution of Strongyloides is unclear. An estimate of 100–370 million people infected worldwide has been proposed; however, inaccuracy of diagnosis, unreliability of prevalence mapping, and the fact that strongyloidiasis remains a neglected disease suggest that the higher figure of more than 300 million cases is likely to be a more accurate estimate. The complexity of Strongyloides life cycle means that laboratory cultures cannot be maintained outside of a host. This currently limits the range of laboratory-based research, which is vital to controlling Strongyloides through environmental alteration or treatment. Successful clinical treatment with antihelminthic drugs has meant that controlling Strongyloides through environmental control, rather than clinical intervention, has been largely overlooked. These control measures may encompass alteration of the soil environment through physical means, such as desiccation or removal of nutrients, or through chemical or biological agents. Repeated antihelminthic treatment of individuals with recurrent strongyloidiasis has not been observed to result in the selection of resistant strains; however, this has not been explicitly demonstrated, and relying on such assumptions in the long-term may prove to be shortsighted. It is ultimately naive to assume that continued administration of antihelminthics will be without any negative long-term effects. In Australia, strongyloidiasis primarily affects Indigenous communities, including communities from arid central Australia. This

  19. Semi-automated knowledge discovery: identifying and profiling human trafficking

    Science.gov (United States)

    Poelmans, Jonas; Elzinga, Paul; Ignatov, Dmitry I.; Kuznetsov, Sergei O.

    2012-11-01

    We propose an iterative and human-centred knowledge discovery methodology based on formal concept analysis. The proposed approach recognizes the important role of the domain expert in mining real-world enterprise applications and makes use of specific domain knowledge, including human intelligence and domain-specific constraints. Our approach was empirically validated at the Amsterdam-Amstelland police to identify suspects and victims of human trafficking in 266,157 suspicious activity reports. Based on guidelines of the Attorney Generals of the Netherlands, we first defined multiple early warning indicators that were used to index the police reports. Using concept lattices, we revealed numerous unknown human trafficking and loverboy suspects. In-depth investigation by the police resulted in a confirmation of their involvement in illegal activities resulting in actual arrestments been made. Our human-centred approach was embedded into operational policing practice and is now successfully used on a daily basis to cope with the vastly growing amount of unstructured information.

  20. Collection and identification of human remains volatiles by non-contact, dynamic airflow sampling and SPME-GC/MS using various sorbent materials.

    Science.gov (United States)

    DeGreeff, Lauryn E; Furton, Kenneth G

    2011-09-01

    Human remains detection canines are used in locating deceased humans in diverse scenarios and environments based on odor produced during the decay process of the human body. It has been established that human remains detection canines are capable of locating human remains specifically, as opposed to living humans or animal remains, thus suggesting a difference in odor between the different sources. This work explores the collection and determination of such odors using a dynamic headspace concentration device. The airflow rate and three sorbent materials-Dukal cotton gauze, Johnson & Johnson cotton-blend gauze, and polyester material-used for odor collection were evaluated using standard compounds. It was determined that higher airflow rates and openly woven material, e.g., Dukal cotton gauze, yielded significantly less total volatile compounds due to compound breakthrough through the sorbent material. Collection from polymer- and cellulose-based materials demonstrated that the molecular backbone of the material is a factor in compound collection as well. Volatiles, including cyclic and straight-chain hydrocarbons, organic acids, sulfides, aldehydes, ketones, and alcohols, were collected from a population of 27 deceased bodies from two collection locations. The common compounds between the subjects were compared and the odor profiles were determined. These odor profiles were compared with those of animal remains and living human subjects collected in the same manner. Principal component analysis showed that the odor profiles of the three sample types were distinct.

  1. The Sommersdorf mummies-An interdisciplinary investigation on human remains from a 17th-19th century aristocratic crypt in southern Germany.

    Science.gov (United States)

    Alterauge, Amelie; Kellinghaus, Manuel; Jackowski, Christian; Shved, Natallia; Rühli, Frank; Maixner, Frank; Zink, Albert; Rosendahl, Wilfried; Lösch, Sandra

    2017-01-01

    Sommersdorf Castle (Bavaria, Germany) is a medieval castle complex which has been inhabited by the aristocratic family von Crailsheim. The deceased were entombed in a crypt located in the parapets underneath the castle's church, resulting in mummification of the bodies. Based on the family chronicle and oral history, identities have been ascribed to the mummies. The aim of the study is therefore to test the accuracy of the historical records in comparison to archaeological, anthropological and genetic data. Today, the crypt houses eleven wooden coffins from the 17th to 19th century AD. In ten of these, mummified and scattered human remains were found. Archive records were studied in order to identify names, ancestry, titles, occupation, date of birth and death, and place of interment of the individuals. The coffins were visually inspected and dated by typo-chronology, and the mummified and scattered skeletal remains were subjected to a physical anthropological examination. In total, the crypt contains the remains of a minimum number of nine individuals, among them three adult males, five adult females and one infant. A detailed scientific examination, including prior conservation, ancient DNA analyses, and computed tomography (CT), was performed on five mummies. By means of the CT data age at death, sex, body height, pathologies, and anatomical variants were investigated. CT analysis further showed that the bodies were naturally mummified. Mitochondrial DNA analyses revealed that the tested individuals are not maternally related. In addition, health, living conditions and circumstances of death of the entombed individuals could be highlighted. Being confronted with the strengths, weaknesses and limitations of each methodological approach, probable identification was achieved in two cases.

  2. The Sommersdorf mummies—An interdisciplinary investigation on human remains from a 17th-19th century aristocratic crypt in southern Germany

    Science.gov (United States)

    Kellinghaus, Manuel; Jackowski, Christian; Shved, Natallia; Rühli, Frank; Maixner, Frank; Zink, Albert; Rosendahl, Wilfried; Lösch, Sandra

    2017-01-01

    Sommersdorf Castle (Bavaria, Germany) is a medieval castle complex which has been inhabited by the aristocratic family von Crailsheim. The deceased were entombed in a crypt located in the parapets underneath the castle’s church, resulting in mummification of the bodies. Based on the family chronicle and oral history, identities have been ascribed to the mummies. The aim of the study is therefore to test the accuracy of the historical records in comparison to archaeological, anthropological and genetic data. Today, the crypt houses eleven wooden coffins from the 17th to 19th century AD. In ten of these, mummified and scattered human remains were found. Archive records were studied in order to identify names, ancestry, titles, occupation, date of birth and death, and place of interment of the individuals. The coffins were visually inspected and dated by typo-chronology, and the mummified and scattered skeletal remains were subjected to a physical anthropological examination. In total, the crypt contains the remains of a minimum number of nine individuals, among them three adult males, five adult females and one infant. A detailed scientific examination, including prior conservation, ancient DNA analyses, and computed tomography (CT), was performed on five mummies. By means of the CT data age at death, sex, body height, pathologies, and anatomical variants were investigated. CT analysis further showed that the bodies were naturally mummified. Mitochondrial DNA analyses revealed that the tested individuals are not maternally related. In addition, health, living conditions and circumstances of death of the entombed individuals could be highlighted. Being confronted with the strengths, weaknesses and limitations of each methodological approach, probable identification was achieved in two cases. PMID:28859116

  3. Global Proteome Analysis Identifies Active Immunoproteasome Subunits in Human Platelets*

    Science.gov (United States)

    Klockenbusch, Cordula; Walsh, Geraldine M.; Brown, Lyda M.; Hoffman, Michael D.; Ignatchenko, Vladimir; Kislinger, Thomas; Kast, Juergen

    2014-01-01

    The discovery of new functions for platelets, particularly in inflammation and immunity, has expanded the role of these anucleate cell fragments beyond their primary hemostatic function. Here, four in-depth human platelet proteomic data sets were generated to explore potential new functions for platelets based on their protein content and this led to the identification of 2559 high confidence proteins. During a more detailed analysis, consistently high expression of the proteasome was discovered, and the composition and function of this complex, whose role in platelets has not been thoroughly investigated, was examined. Data set mining resulted in identification of nearly all members of the 26S proteasome in one or more data sets, except the β5 subunit. However, β5i, a component of the immunoproteasome, was identified. Biochemical analyses confirmed the presence of all catalytically active subunits of the standard 20S proteasome and immunoproteasome in human platelets, including β5, which was predominantly found in its precursor form. It was demonstrated that these components were assembled into the proteasome complex and that standard proteasome as well as immunoproteasome subunits were constitutively active in platelets. These findings suggest potential new roles for platelets in the immune system. For example, the immunoproteasome may be involved in major histocompatibility complex I (MHC I) peptide generation, as the MHC I machinery was also identified in our data sets. PMID:25146974

  4. Global proteome analysis identifies active immunoproteasome subunits in human platelets.

    Science.gov (United States)

    Klockenbusch, Cordula; Walsh, Geraldine M; Brown, Lyda M; Hoffman, Michael D; Ignatchenko, Vladimir; Kislinger, Thomas; Kast, Juergen

    2014-12-01

    The discovery of new functions for platelets, particularly in inflammation and immunity, has expanded the role of these anucleate cell fragments beyond their primary hemostatic function. Here, four in-depth human platelet proteomic data sets were generated to explore potential new functions for platelets based on their protein content and this led to the identification of 2559 high confidence proteins. During a more detailed analysis, consistently high expression of the proteasome was discovered, and the composition and function of this complex, whose role in platelets has not been thoroughly investigated, was examined. Data set mining resulted in identification of nearly all members of the 26S proteasome in one or more data sets, except the β5 subunit. However, β5i, a component of the immunoproteasome, was identified. Biochemical analyses confirmed the presence of all catalytically active subunits of the standard 20S proteasome and immunoproteasome in human platelets, including β5, which was predominantly found in its precursor form. It was demonstrated that these components were assembled into the proteasome complex and that standard proteasome as well as immunoproteasome subunits were constitutively active in platelets. These findings suggest potential new roles for platelets in the immune system. For example, the immunoproteasome may be involved in major histocompatibility complex I (MHC I) peptide generation, as the MHC I machinery was also identified in our data sets. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Identifying and annotating human bifunctional RNAs reveals their versatile functions.

    Science.gov (United States)

    Chen, Geng; Yang, Juan; Chen, Jiwei; Song, Yunjie; Cao, Ruifang; Shi, Tieliu; Shi, Leming

    2016-10-01

    Bifunctional RNAs that possess both protein-coding and noncoding functional properties were less explored and poorly understood. Here we systematically explored the characteristics and functions of such human bifunctional RNAs by integrating tandem mass spectrometry and RNA-seq data. We first constructed a pipeline to identify and annotate bifunctional RNAs, leading to the characterization of 132 high-confidence bifunctional RNAs. Our analyses indicate that bifunctional RNAs may be involved in human embryonic development and can be functional in diverse tissues. Moreover, bifunctional RNAs could interact with multiple miRNAs and RNA-binding proteins to exert their corresponding roles. Bifunctional RNAs may also function as competing endogenous RNAs to regulate the expression of many genes by competing for common targeting miRNAs. Finally, somatic mutations of diverse carcinomas may generate harmful effect on corresponding bifunctional RNAs. Collectively, our study not only provides the pipeline for identifying and annotating bifunctional RNAs but also reveals their important gene-regulatory functions.

  6. The human vascular endothelial cell line HUV-EC-C harbors the integrated HHV-6B genome which remains stable in long term culture

    OpenAIRE

    Shioda, Setsuko; Kasai, Fumio; Ozawa, Midori; Hirayama, Noriko; Satoh, Motonobu; Kameoka, Yousuke; Watanabe, Ken; Shimizu, Norio; Tang, Huamin; Mori, Yasuko; Kohara, Arihiro

    2017-01-01

    Human herpes virus 6 (HHV-6) is a common human pathogen that is most often detected in hematopoietic cells. Although human cells harboring chromosomally integrated HHV-6 can be generated in vitro, the availability of such cell lines originating from in vivo tissues is limited. In this study, chromosomally integrated HHV-6B has been identified in a human vascular endothelial cell line, HUV-EC-C (IFO50271), derived from normal umbilical cord tissue. Sequence analysis revealed that the viral gen...

  7. Identifying Human Factors Issues in Aircraft Maintenance Operations

    Science.gov (United States)

    Veinott, Elizabeth S.; Kanki, Barbara G.; Shafto, Michael G. (Technical Monitor)

    1995-01-01

    Maintenance operations incidents submitted to the Aviation Safety Reporting System (ASRS) between 1986-1992 were systematically analyzed in order to identify issues relevant to human factors and crew coordination. This exploratory analysis involved 95 ASRS reports which represented a wide range of maintenance incidents. The reports were coded and analyzed according to the type of error (e.g, wrong part, procedural error, non-procedural error), contributing factors (e.g., individual, within-team, cross-team, procedure, tools), result of the error (e.g., aircraft damage or not) as well as the operational impact (e.g., aircraft flown to destination, air return, delay at gate). The main findings indicate that procedural errors were most common (48.4%) and that individual and team actions contributed to the errors in more than 50% of the cases. As for operational results, most errors were either corrected after landing at the destination (51.6%) or required the flight crew to stop enroute (29.5%). Interactions among these variables are also discussed. This analysis is a first step toward developing a taxonomy of crew coordination problems in maintenance. By understanding what variables are important and how they are interrelated, we may develop intervention strategies that are better tailored to the human factor issues involved.

  8. Retrieving chronological age from dental remains of early fossil hominins to reconstruct human growth in the past.

    Science.gov (United States)

    Dean, M Christopher

    2010-10-27

    A chronology of dental development in Pan troglodytes is arguably the best available model with which to compare and contrast reconstructed dental chronologies of the earliest fossil hominins. Establishing a time scale for growth is a requirement for being able to make further comparative observations about timing and rate during both dento-skeletal growth and brain growth. The absolute timing of anterior tooth crown and root formation appears not to reflect the period of somatic growth. In contrast, the molar dentition best reflects changes to the total growth period. Earlier initiation of molar mineralization, shorter crown formation times, less root length formed at gingival emergence into functional occlusion are cumulatively expressed as earlier ages at molar eruption. Things that are similar in modern humans and Pan, such as the total length of time taken to form individual teeth, raise expectations that these would also have been the same in fossil hominins. The best evidence there is from the youngest fossil hominin specimens suggests a close resemblance to the model for Pan but also hints that Gorilla may be a better developmental model for some. A mosaic of great ape-like features currently best describes the timing of early hominin dental development.

  9. Three-dimensional Invasion of Human Glioblastoma Cells Remains Unchanged by X-ray and Carbon Ion Irradiation In Vitro

    Energy Technology Data Exchange (ETDEWEB)

    Eke, Iris; Storch, Katja; Kaestner, Ina; Vehlow, Anne [OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany); Faethe, Christina; Mueller-Klieser, Wolfgang [Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz (Germany); Taucher-Scholz, Gisela [Department of Biophysics, GSI Helmholtz Center for Heavy Ion Research, Darmstadt (Germany); Temme, Achim; Schackert, Gabriele [Section of Experimental Neurosurgery/Tumor Immunology, Department of Neurosurgery, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden (Germany); Cordes, Nils, E-mail: Nils.Cordes@Oncoray.de [OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany); Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany)

    2012-11-15

    Purpose: Cell invasion represents one of the major determinants that treatment has failed for patients suffering from glioblastoma. Contrary findings have been reported for cell migration upon exposure to ionizing radiation. Here, the migration and invasion capability of glioblastoma cells on and in collagen type I were evaluated upon irradiation with X-rays or carbon ions. Methods and Materials: Migration on and invasion in collagen type I were evaluated in four established human glioblastoma cell lines exposed to either X-rays or carbon ions. Furthermore, clonogenic radiation survival, proliferation (5-bromo-2-deoxyuridine positivity), DNA double-strand breaks ({gamma}H2AX/53BP1-positive foci), and expression of invasion-relevant proteins (eg, {beta}1 integrin, FAK, MMP2, and MMP9) were explored. Migration and invasion assays for primary glioblastoma cells also were carried out with X-ray irradiation. Results: Neither X-ray nor carbon ion irradiation affected glioblastoma cell migration and invasion, a finding similarly observed in primary glioblastoma cells. Intriguingly, irradiated cells migrated unhampered, despite DNA double-strand breaks and reduced proliferation. Clonogenic radiation survival was increased when cells had contact with extracellular matrix. Specific inhibition of the {beta}1 integrin or proliferation-associated signaling molecules revealed a critical function of JNK, PI3K, and p38 MAPK in glioblastoma cell invasion. Conclusions: These findings indicate that X-rays and carbon ion irradiation effectively reduce proliferation and clonogenic survival without modifying the migration and invasion ability of glioblastoma cells in a collagen type I environment. Addition of targeted agents against members of the MAPK and PI3K signaling axis to conventional chemoradiation therapy seems potentially useful to optimize glioblastoma therapy.

  10. Differences between biological and chronological age-at-death in human skeletal remains: A change of perspective.

    Science.gov (United States)

    Couoh, Lourdes R

    2017-08-01

    This analysis seeks to determine whether differences between real and estimated chronological age (CA) with biological age (BA) in skeletal individuals reflect variability in aging. A total of 87 individuals of two samples, ranging from 20 to 94 years old, were analyzed. One, partially documented, belongs to a Mexican skeletal collection dating to the 20th century; the other is an assemblage of prehispanic individuals from different archaeological sites. In all specimens, the tooth annulation method (TCA) was applied to estimate CA, while-excluding individuals older than 80 years-auricular surface (AS) and pubic symphysis (PS) methods were used to estimate BA. Statistical analyses were conducted to identify correlations and significance of the differences between CA vs. TCA, CA vs. AS/PS, TCA vs. AS/PS. Sex of individuals was assessed for its influence in aging. The use of TCA to estimate CA was successful for most individuals. A strong correlation was found between CA vs. TCA, CA vs. AS/PS, TCA vs. AS/PS and their differences were significant but variation in these were found when assessed by separate age groups. Sex did not influence such differences. TCA can be used to estimate CA and its differences with BA, being less than 10 years, are similar to those found in living populations. Differences between CA and BA are due to intra-population variability, which could be the consequence of individual differences in aging. More research is needed to have confidence that under- and overestimations of BA are indicators of aging variability at the level of the individual. © 2017 Wiley Periodicals, Inc.

  11. Human remains from the Moravian Gravettian. Morphology and taphonomy of additional elements from Dolní Vĕstonice II and Pavlov I

    Czech Academy of Sciences Publication Activity Database

    Trinkaus, E.; Svoboda, Jiří; Wojtal, P.; Nývltová Fišáková, Miriam; Wilczyński, J.

    2010-01-01

    Roč. 20, č. 6 (2010), s. 645-669 ISSN 1047-482X Institutional research plan: CEZ:AV0Z80010507 Keywords : Dolní Věstonice * Pavlov * Gravettian * human remains * morphology Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 0.802, year: 2010

  12. Individual human scent as a forensic identifier using mantrailing.

    Science.gov (United States)

    Woidtke, Leif; Dreßler, Jan; Babian, Carsten

    2018-01-01

    Specially trained dogs have long been used by law enforcement agencies to help in criminal investigations and in searching for missing persons. Still, it is unclear which components of human scent released into the environment contribute to successful searches of individuals. In this study, saliva and axillary sweat samples were taken from a total of 190 people. Additionally, DNA was extracted from whole blood of seven different people and used as an odour sample as well. Overall 675 tests (trails) were performed during a period of 18 months. The ability to track individuals with the odour samples mentioned above was examined with seven dogs, four of which were specially-trained dogs (mantrailer) from the Saxony Police. Results indicated that specially-trained police dogs can track a person with an average success rate of 82% and correctly identify the absence of an odour track with an average success rate of 97% under various conditions. Private rescue dogs were less successful with an average success rate of 65% and 75% respectively. These data suggest that the potential error rate of a well-trained handler team is low and can be a useful tool for law enforcement personnel. Saliva, as a reference odour source, was found to be particularly suitable for the search. The results of the study suggest that the components contained in axillary sweat, saliva and DNA extracted from whole blood are sufficient, serving as a key stimulus for individualized searches. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Human-automation collaboration in manufacturing: identifying key implementation factors

    OpenAIRE

    Charalambous, George; Fletcher, Sarah; Webb, Philip

    2013-01-01

    Human-automation collaboration refers to the concept of human operators and intelligent automation working together interactively within the same workspace without conventional physical separation. This concept has commanded significant attention in manufacturing because of the potential applications, such as the installation of large sub-assemblies. However, the key human factors relevant to human-automation collaboration have not yet been fully investigated. To maximise effective implement...

  14. Chronology of the Grotte du Renne (France) and implications for the context of ornaments and human remains within the Châtelperronian.

    Science.gov (United States)

    Higham, Thomas; Jacobi, Roger; Julien, Michèle; David, Francine; Basell, Laura; Wood, Rachel; Davies, William; Ramsey, Christopher Bronk

    2010-11-23

    There is extensive debate concerning the cognitive and behavioral adaptation of Neanderthals, especially in the period when the earliest anatomically modern humans dispersed into Western Europe, around 35,000-40,000 B.P. The site of the Grotte du Renne (at Arcy-sur-Cure) is of great importance because it provides the most persuasive evidence for behavioral complexity among Neanderthals. A range of ornaments and tools usually associated with modern human industries, such as the Aurignacian, were excavated from three of the Châtelperronian levels at the site, along with Neanderthal fossil remains (mainly teeth). This extremely rare occurrence has been taken to suggest that Neanderthals were the creators of these items. Whether Neanderthals independently achieved this level of behavioral complexity and whether this was culturally transmitted or mimicked via incoming modern humans has been contentious. At the heart of this discussion lies an assumption regarding the integrity of the excavated remains. One means of testing this is by radiocarbon dating; however, until recently, our ability to generate both accurate and precise results for this period has been compromised. A series of 31 accelerator mass spectrometry ultrafiltered dates on bones, antlers, artifacts, and teeth from six key archaeological levels shows an unexpected degree of variation. This suggests that some mixing of material may have occurred, which implies a more complex depositional history at the site and makes it difficult to be confident about the association of artifacts with human remains in the Châtelperronian levels.

  15. An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing

    Science.gov (United States)

    Orabona, Guilherme; Morgan, Thomas; Haataja, Ritva; Hallman, Mikko; Puttonen, Hilkka; Menon, Ramkumar; Kuczynski, Edward; Norwitz, Errol; Snegovskikh, Victoria; Palotie, Aarno; Fellman, Vineta; DeFranco, Emily A.; Chaudhari, Bimal P.; McGregor, Tracy L.; McElroy, Jude J.; Oetjens, Matthew T.; Teramo, Kari; Borecki, Ingrid; Fay, Justin; Muglia, Louis

    2011-01-01

    Coordination of fetal maturation with birth timing is essential for mammalian reproduction. In humans, preterm birth is a disorder of profound global health significance. The signals initiating parturition in humans have remained elusive, due to divergence in physiological mechanisms between humans and model organisms typically studied. Because of relatively large human head size and narrow birth canal cross-sectional area compared to other primates, we hypothesized that genes involved in parturition would display accelerated evolution along the human and/or higher primate phylogenetic lineages to decrease the length of gestation and promote delivery of a smaller fetus that transits the birth canal more readily. Further, we tested whether current variation in such accelerated genes contributes to preterm birth risk. Evidence from allometric scaling of gestational age suggests human gestation has been shortened relative to other primates. Consistent with our hypothesis, many genes involved in reproduction show human acceleration in their coding or adjacent noncoding regions. We screened >8,400 SNPs in 150 human accelerated genes in 165 Finnish preterm and 163 control mothers for association with preterm birth. In this cohort, the most significant association was in FSHR, and 8 of the 10 most significant SNPs were in this gene. Further evidence for association of a linkage disequilibrium block of SNPs in FSHR, rs11686474, rs11680730, rs12473870, and rs1247381 was found in African Americans. By considering human acceleration, we identified a novel gene that may be associated with preterm birth, FSHR. We anticipate other human accelerated genes will similarly be associated with preterm birth risk and elucidate essential pathways for human parturition. PMID:21533219

  16. Paleohistology and the study of human remains: past, present and future approaches / La paleohistologia y el estudio de restos humanos: aproximaciones pasadas presentes y futuras

    Directory of Open Access Journals (Sweden)

    Sandra Assis

    2015-12-01

    Full Text Available The invention of the microscope revolutionized the course of human knowledge. This instrument changed the face of science and of previous beliefs, expanded the horizons of knowledge, and challenged philosophical and scientific thought, especially in the field of natural sciences and medicine. In the domain of bioarchaeology, the introduction of histological techniques was important; not only to identify body tissues and to diagnose diseases in mummified remains, but also to understand bone and teeth microstructure, and associated patterns of response to environmental constraints. In this paper a critical review of the major contributions of histology to the growing body of knowledge in paleopathology and bioarchaeology will be presented, focusing on the current multiple applications of microscopy, its limitations, and its future challenges. KEY WORDS microscopy; dry bone remains; multiple approaches   La invención del microscopio ha revolucionado el curso del conocimiento humano. Este instrumento cambió la “cara” de la ciencia y de las creencias anteriores, amplió los horizontes del conocimiento y retó al pensamiento filosófico y científico, especialmente en el campo de las ciencias naturales y la medicina. En el dominio de la bioarqueología, la introducción de técnicas histológicas fue determinante, no sólo para identificar los tejidos del cuerpo y diagnosticar enfermedades en restos momificados, sino también para comprender la microestructura y dinámica de los huesos y los dientes, y los patrones asociados de respuesta a las restricciones ambientales. En este trabajo se presenta una revisión crítica de las principales contribuciones de la histología al creciente cuerpo de conocimientos de la paleopatología y la bioarqueología, con énfasis en las actuales aplicaciones de la microscopía, sus limitaciones y los desafíos para el futuro. PALABRAS CLAVE microscopía, restos humanos, múltiples enfoques

  17. Integrated DNA and fingerprint analyses in the identification of 60-year-old mummified human remains discovered in an Alaskan glacier.

    Science.gov (United States)

    Loreille, Odile M; Parr, Ryan L; McGregor, Kevin A; Fitzpatrick, Colleen M; Lyon, Chriss; Yang, Dongya Y; Speller, Camilla F; Grimm, Michael R; Grimm, Michael J; Irwin, Jodi A; Robinson, Edward M

    2010-05-01

    This report describes the identification of a merchant mariner who perished in 1948 when Northwest Airlines Flight 4422, a DC-4 carrying 24 seamen and six crew members crashed into Mount Sanford, Alaska. Fifty-one years later, a human forearm and hand were found close by the wreckage of the plane, prompting identification efforts using DNA and fingerprints. There were significant challenges to both the fingerprint and DNA analyses. The hand was badly desiccated, making fingerprint friction-ridge detail almost invisible and the remains had been embalmed upon discovery, making DNA amplification difficult. We present the results of an interdisciplinary approach that successfully addressed these challenges and ultimately led to the identification of the remains. These efforts relied on efficient fingerprint rejuvenation and imaging techniques that improved print resolution, as well as new DNA extraction techniques optimized for aggressively embalmed remains.

  18. External auditory exostoses in the Xuchang and Xujiayao human remains: Patterns and implications among eastern Eurasian Middle and Late Pleistocene crania.

    Science.gov (United States)

    Trinkaus, Erik; Wu, Xiu-Jie

    2017-01-01

    In the context of Middle and Late Pleistocene eastern Eurasian human crania, the external auditory exostoses (EAE) of the late archaic Xuchang 1 and 2 and the Xujiayao 15 early Late Pleistocene human temporal bones are described. Xujiayao 15 has small EAE (Grade 1), Xuchang 1 presents bilateral medium EAE (Grade 2), and Xuchang 2 exhibits bilaterally large EAE (Grade 3), especially on the right side. These cranial remains join the other eastern Eurasian later Pleistocene humans in providing frequencies of 61% (N = 18) and 58% (N = 12) respectively for archaic and early modern human samples. These values are near the upper limits of recent human frequencies, and they imply frequent aquatic exposure among these Pleistocene humans. In addition, the medial extents of the Xuchang 1 and 2 EAE would have impinged on their tympanic membranes, and the large EAE of Xuchang 2 would have resulted in cerumen impaction. Both effects would have produced conductive hearing loss, a serious impairment in a Pleistocene foraging context.

  19. Interaction Profiling Identifies the Human Nuclear Exosome Targeting Complex

    DEFF Research Database (Denmark)

    Lubas, Michal Szymon; Christensen, Marianne Skovgaard; Kristiansen, Maiken Søndergaard

    2011-01-01

    from nucleoli, and consistently NEXT is specifically required for the exosomal degradation of promoter upstream transcripts (PROMPTs). We also detect putative homolog TRAMP subunits hTRF4-2 (Trf4p) and ZCCHC7 (Air2p) in hRRP6 and hMTR4 precipitates. However, at least ZCCHC7 function is restricted...... to nucleoli. Our results suggest that human nuclear exosome degradation pathways comprise modules of spatially organized cofactors that diverge from the yeast model....

  20. Digging up the recent Spanish memory: genetic identification of human remains from mass graves of the Spanish Civil War and posterior dictatorship.

    Science.gov (United States)

    Baeta, Miriam; Núñez, Carolina; Cardoso, Sergio; Palencia-Madrid, Leire; Herrasti, Lourdes; Etxeberria, Francisco; de Pancorbo, Marian M

    2015-11-01

    The Spanish Civil War (1936-1939) and posterior dictatorship (until 1970s) stands as one of the major conflicts in the recent history of Spain. It led to nearly two hundred thousand men and women executed or murdered extra-judicially or after dubious legal procedures. Nowadays, most of them remain unidentified or even buried in irretraceable mass graves across Spain. Here, we present the genetic identification of human remains found in 26 mass graves located in Northern Spain. A total of 252 post-mortem remains were analyzed and compared to 186 relatives, allowing the identification of 87 victims. Overall, a significant success of DNA profiling was reached, since informative profiles (≥ 12 STRs and/or mitochondrial DNA profile) were obtained in 85.71% of the remains. This high performance in DNA profiling from challenging samples demonstrated the efficacy of DNA extraction and amplification methods used herein, given that only around 14.29% of the samples did not provide an informative genetic profile for the analysis performed, probably due to the presence of degraded and/or limited DNA in these remains. However, this study shows a partial identification success rate, which is clearly a consequence of the lack of both appropriate family members for genetic comparisons and accurate information about the victims' location. Hence, further perseverance in the exhumation of other intact graves as well as in the search of more alleged relatives is crucial in order to facilitate and increase the number of genetic identifications. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Human group C rotaviruses identified in Kenya | Mwenda | East ...

    African Journals Online (AJOL)

    Subjects and Methods:Faecal samples were collected from 119 infants and young children with diarrhoea and were analysed by commercial ELISA and polyacrylamide gel electrophoresis (SDS-PAGE) to identify possible non-group A rotaviruses. Extraction of any potential rrotavirus double-stranded RNA from faeces amd ...

  2. Elimination of remaining undifferentiated induced pluripotent stem cells in the process of human cardiac cell sheet fabrication using a methionine-free culture condition.

    Science.gov (United States)

    Matsuura, Katsuhisa; Kodama, Fumiko; Sugiyama, Kasumi; Shimizu, Tatsuya; Hagiwara, Nobuhisa; Okano, Teruo

    2015-03-01

    Cardiac tissue engineering is a promising method for regenerative medicine. Although we have developed human cardiac cell sheets by integration of cell sheet-based tissue engineering and scalable bioreactor culture, the risk of contamination by induced pluripotent stem (iPS) cells in cardiac cell sheets remains unresolved. In the present study, we established a novel culture method to fabricate human cardiac cell sheets with a decreased risk of iPS cell contamination while maintaining viabilities of iPS cell-derived cells, including cardiomyocytes and fibroblasts, using a methionine-free culture condition. When cultured in the methionine-free condition, human iPS cells did not survive without feeder cells and could not proliferate or form colonies on feeder cells or in coculture with cells for cardiac cell sheet fabrication. When iPS cell-derived cells after the cardiac differentiation were transiently cultured in the methionine-free condition, gene expression of OCT3/4 and NANOG was downregulated significantly compared with that in the standard culture condition. Furthermore, in fabricated cardiac cell sheets, spontaneous and synchronous beating was observed in the whole area while maintaining or upregulating the expression of various cardiac and extracellular matrix genes. These findings suggest that human iPS cells are methionine dependent and a methionine-free culture condition for cardiac cell sheet fabrication might reduce the risk of iPS cell contamination.

  3. Forensically Important Blow Flies Chrysomya pinguis, C. villeneuvi, and Lucilia porphyrina (Diptera: Calliphoridae) in a Case of Human Remains in Thailand

    Science.gov (United States)

    Monum, Tawatchai; Sukontason, Kabkaew L.; Sribanditmongkol, Pongruk; Sukontason, Kom; Samerjai, Chutharat; Limsopatham, Kwankamol; Suwannayod, Suttida; Klong-klaew, Tunwadee; Wannasan, Anchalee

    2017-01-01

    This is the first study to report Chrysomya pinguis (Walker) and Lucilia porphyrina (Walker) (Diptera: Calliphoridae) as forensically important blow fly species from human cadavers in Thailand, in addition to Chrysomya villeneuvi (Patton) already known in Thailand. In 2016, a fully decomposed body of an unknown adult male was discovered in a high mountainous forest during winter in Chiang Mai province. The remains were infested heavily with thousands of blow fly larvae feeding simultaneously on them. Morphological identification of adults reared from the larvae, and molecular analysis based on sequencing of 1,247 bp partial mitochondrial cytochrome c oxidase subunit 1 gene (CO1) of the larvae and puparia, confirmed the above mentioned 3 species. The approving forensic fly evidence by molecular approach was described for the first time in Thailand. Moreover, neighbor-joining phylogenetic analysis of the CO1 was performed to compare the relatedness of the species, thereby affirming the accuracy of identification. As species of entomofauna varies among cases in different geographic and climatic circumstances, C. pinguis and L. porphyrina were added to the list of Thai forensic entomology caseworks, including colonizers of human remains in open, high mountainous areas during winter. Further research should focus on these 3 species, for which no developmental data are currently available. PMID:28285509

  4. Human genetics as a tool to identify progranulin regulators.

    Science.gov (United States)

    Nicholson, Alexandra M; Finch, NiCole A; Rademakers, Rosa

    2011-11-01

    Frontotemporal lobar degeneration (FTLD) is a common neurodegenerative disorder that predominantly affects individuals under the age of 65. It is known that the most common pathological subtype is FTLD with TAR DNA-binding protein 43 inclusions (FTLD-TDP). FTLD has a strong genetic component with about 50% of cases having a positive family history. Mutations identified in the progranulin gene (GRN) have been shown to cause FTLD-TDP as a result of progranulin haploinsufficiency. These findings suggest a progranulin-dependent mechanism in this pathological FTLD subtype. Thus, identifying regulators of progranulin levels is essential for new therapies and treatments for FTLD and related disorders. In this review, we discuss the role of genetic studies in identifying progranulin regulators, beginning with the discovery of pathogenic GRN mutations and additional GRN risk variants. We also cover more recent genetic advances, including the detection of variants in the transmembrane protein 106 B gene that increase FTLD-TDP risk presumably by modulating progranulin levels and the identification of a potential progranulin receptor, sortilin. This review highlights the importance of genetic studies in the context of FTLD and further emphasizes the need for future genetic and cell biology research to continue the effort in finding a cure for progranulin-related diseases.

  5. Comparative genetics: synergizing human and NOD mouse studies for identifying genetic causation of type 1 diabetes.

    Science.gov (United States)

    Driver, John P; Chen, Yi-Guang; Mathews, Clayton E

    2012-01-01

    Although once widely anticipated to unlock how human type 1 diabetes (T1D) develops, extensive study of the nonobese diabetic (NOD) mouse has failed to yield effective treatments for patients with the disease. This has led many to question the usefulness of this animal model. While criticism about the differences between NOD and human T1D is legitimate, in many cases disease in both species results from perturbations modulated by the same genes or different genes that function within the same biological pathways. Like in humans, unusual polymorphisms within an MHC class II molecule contributes the most T1D risk in NOD mice. This insight supports the validity of this model and suggests the NOD has been improperly utilized to study how to cure or prevent disease in patients. Indeed, clinical trials are far from administering T1D therapeutics to humans at the same concentration ranges and pathological states that inhibit disease in NOD mice. Until these obstacles are overcome it is premature to label the NOD mouse a poor surrogate to test agents that cure or prevent T1D. An additional criticism of the NOD mouse is the past difficulty in identifying genes underlying T1D using conventional mapping studies. However, most of the few diabetogenic alleles identified to date appear relevant to the human disorder. This suggests that rather than abandoning genetic studies in NOD mice, future efforts should focus on improving the efficiency with which diabetes susceptibility genes are detected. The current review highlights why the NOD mouse remains a relevant and valuable tool to understand the genes and their interactions that promote autoimmune diabetes and therapeutics that inhibit this disease. It also describes a new range of technologies that will likely transform how the NOD mouse is used to uncover the genetic causes of T1D for years to come.

  6. Interaction of Proteins Identified in Human Thyroid Cells

    Science.gov (United States)

    Pietsch, Jessica; Riwaldt, Stefan; Bauer, Johann; Sickmann, Albert; Weber, Gerhard; Grosse, Jirka; Infanger, Manfred; Eilles, Christoph; Grimm, Daniela

    2013-01-01

    Influence of gravity forces on the regulation of protein expression by healthy and malignant thyroid cells was studied with the aim to identify protein interactions. Western blot analyses of a limited number of proteins suggested a time-dependent regulation of protein expression by simulated microgravity. After applying free flow isoelectric focusing and mass spectrometry to search for differently expressed proteins by thyroid cells exposed to simulated microgravity for three days, a considerable number of candidates for gravi-sensitive proteins were detected. In order to show how proteins sensitive to microgravity could directly influence other proteins, we investigated all polypeptide chains identified with Mascot scores above 100, looking for groups of interacting proteins. Hence, UniProtKB entry numbers of all detected proteins were entered into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and processed. The program indicated that we had detected various groups of interacting proteins in each of the three cell lines studied. The major groups of interacting proteins play a role in pathways of carbohydrate and protein metabolism, regulation of cell growth and cell membrane structuring. Analyzing these groups, networks of interaction could be established which show how a punctual influence of simulated microgravity may propagate via various members of interaction chains. PMID:23303277

  7. Interaction of Proteins Identified in Human Thyroid Cells

    Directory of Open Access Journals (Sweden)

    Jessica Pietsch

    2013-01-01

    Full Text Available Influence of gravity forces on the regulation of protein expression by healthy and malignant thyroid cells was studied with the aim to identify protein interactions. Western blot analyses of a limited number of proteins suggested a time-dependent regulation of protein expression by simulated microgravity. After applying free flow isoelectric focusing and mass spectrometry to search for differently expressed proteins by thyroid cells exposed to simulated microgravity for three days, a considerable number of candidates for gravi-sensitive proteins were detected. In order to show how proteins sensitive to microgravity could directly influence other proteins, we investigated all polypeptide chains identified with Mascot scores above 100, looking for groups of interacting proteins. Hence, UniProtKB entry numbers of all detected proteins were entered into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING and processed. The program indicated that we had detected various groups of interacting proteins in each of the three cell lines studied. The major groups of interacting proteins play a role in pathways of carbohydrate and protein metabolism, regulation of cell growth and cell membrane structuring. Analyzing these groups, networks of interaction could be established which show how a punctual influence of simulated microgravity may propagate via various members of interaction chains.

  8. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    Science.gov (United States)

    Adams, Hieab HH; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura ME; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher RK; Cuellar-Partida, Gabriel; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David CM; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Olde Loohuis, Loes M; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein MJ; Van Eijk, Kristel R; Van Erp, Theo GM; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco JC; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald HH; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, WT; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda WJH; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Valdés Hernández, Maria C; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic JA; Van Duijn, Cornelia M; Van Haren, Neeltje EM; Van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton JM; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth. PMID:27694991

  9. Human-mediated extirpation of the unique Chatham Islands sea lion and implications for the conservation management of remaining New Zealand sea lion populations.

    Science.gov (United States)

    Rawlence, Nicolas J; Collins, Catherine J; Anderson, Christian N K; Maxwell, Justin J; Smith, Ian W G; Robertson, Bruce C; Knapp, Michael; Horsburgh, Katherine Ann; Stanton, Jo-Ann L; Scofield, R Paul; Tennyson, Alan J D; Matisoo-Smith, Elizabeth A; Waters, Jonathan M

    2016-08-01

    While terrestrial megafaunal extinctions have been well characterized worldwide, our understanding of declines in marine megafauna remains limited. Here, we use ancient DNA analyses of prehistoric (extinct within 200 years due to overhunting, paralleling the extirpation of a similarly large endemic mainland population. Whole mitogenomic analyses confirm substantial intraspecific diversity among prehistoric lineages. Demographic models suggest that even low harvest rates would likely have driven rapid extinction of these lineages. This study indicates that surviving Phocarctos populations are remnants of a once diverse and widespread sea lion assemblage, highlighting dramatic human impacts on endemic marine biodiversity. Our findings also suggest that Phocarctos bycatch in commercial fisheries may contribute to the ongoing population decline. © 2016 John Wiley & Sons Ltd.

  10. NKp46 identifies an NKT cell subset susceptible to leukemic transformation in mouse and human

    Science.gov (United States)

    Yu, Jianhua; Mitsui, Takeki; Wei, Min; Mao, Hsiaoyin; Butchar, Jonathan P.; Shah, Mithun Vinod; Zhang, Jianying; Mishra, Anjali; Alvarez-Breckenridge, Christopher; Liu, Xingluo; Liu, Shujun; Yokohama, Akihiko; Trotta, Rossana; Marcucci, Guido; Benson, Don M.; Loughran, Thomas P.; Tridandapani, Susheela; Caligiuri, Michael A.

    2011-01-01

    IL-15 may have a role in the development of T cell large granular lymphocyte (T-LGL) or NKT leukemias. However, the mechanisms of action and the identity of the cell subset that undergoes leukemic transformation remain elusive. Here we show that in both mice and humans, NKp46 expression marks a minute population of WT NKT cells with higher activity and potency to become leukemic. Virtually 100% of T-LGL leukemias in IL-15 transgenic mice expressed NKp46, as did a majority of human T-LGL leukemias. The minute NKp46+ NKT population, but not the NKp46– NKT population, was selectively expanded by overexpression of endogenous IL-15. Importantly, IL-15 transgenic NKp46– NKT cells did not become NKp46+ in vivo, suggesting that NKp46+ T-LGL leukemia cells were the malignant counterpart of the minute WT NKp46+ NKT population. Mechanistically, NKp46+ NKT cells possessed higher responsiveness to IL-15 in vitro and in vivo compared with that of their NKp46– NKT counterparts. Furthermore, interruption of IL-15 signaling using a neutralizing antibody could prevent LGL leukemia in IL-15 transgenic mice. Collectively, our data demonstrate that NKp46 identifies a functionally distinct NKT subset in mice and humans that appears to be directly susceptible to leukemic transformation when IL-15 is overexpressed. Thus, IL-15 signaling and NKp46 may be useful targets in the treatment of patients with T-LGL or NKT leukemia. PMID:21364281

  11. Direct U-series analysis of the Lezetxiki humerus reveals a Middle Pleistocene age for human remains in the Basque Country (northern Iberia).

    Science.gov (United States)

    de-la-Rúa, Concepción; Altuna, Jesús; Hervella, Monserrat; Kinsley, Leslie; Grün, Rainer

    2016-04-01

    In 1964, a human humerus was found in a sedimentary deposit in Lezetxiki Cave (Basque Country, northern Iberia). The first studies on the stratigraphy, associated mammal faunal remains and lithic implements placed the deposits containing the humerus into the Riss glacial stage. Direct chronometric evidence has so far been missing, and the previous chronostratigraphic framework and faunal dating gave inconsistent results. Here we report laser ablation U-series analyses on the humerus yielding a minimum age of 164 ± 9 ka, corresponding to MIS 6. This is the only direct dating analysis of the Lezetxiki humerus and confirms a Middle Pleistocene age for this hominin fossil. Morphometric analyses suggest that the Lezetxiki humerus has close affinities to other Middle Pleistocene archaic hominins, such as those from La Sima de los Huesos at Atapuerca. This emphasizes the significance of the Lezetxiki fossil within the populations that predate the Neanderthals in south-western Europe. It is thus an important key fossil for the understanding of human evolution in Europe during the Middle Pleistocene, a time period when a great morphological diversity is observed but whose phylogenetic meaning is not yet fully understood. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    OpenAIRE

    Adams, Hieab HH; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Renter��a, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivi��res, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjus...

  13. Precise isotope ratio and multielement determination in prehistoric and historic human skeletal remains by HR-ICPMS - a novel application to shed light onto anthropological and archaeological questions

    International Nuclear Information System (INIS)

    Watkins, M.

    2000-12-01

    The primary aim of the presented work was the analytical setup for fast (including high sample throughput for statistical evaluation), precise and accurate measurement of strontium isotope ratios using HR-ICPMS (high-resolution inductively coupled plasma mass spectrometry) and their application to ancient human skeletal remains from different localities for the reconstruction of migration processes. Soils and plants are in isotopic equilibrium with local source rock and show therefore the same isotopic ratios for strontium (87Sr/86Sr). Dietary strontium incorporation varies for different body materials (teeth, muscle, bone, etc.) and repository periods depend on the different strontium turnover rates. Accordingly, strontium isotope analysis can provide important data for studying human or animal migration and mobility. An important issue will be addressed: the problem of strontium isotope ratio measurement reliability and the problem of post-mortem alterations. Thus a basic part of this interdisciplinary project is dealing with the systematic evaluation of diagenetic changes of the microstructure in human bone samples - including sample uptake and preparation. Different invasive histological techniques will be applied for further clarification. Newly developed chemical methods give us the opportunity to obtain details on ancient population mobility also in skeletal series of extreme fragmentary character, which usually restricts the macro-morphological approach. Since it is evident that strontium in teeth is only incorporated during childhood whereas strontium uptake in bones is constant, an intra-individual comparison of bone and teeth samples will answer the question whether teeth are indeed 'archives of the childhood'. The introduction of an analytical system allowing online matrix separation by High Performance Ion Chromatography (HPIC) and subsequent measurement of strontium isotope ratios by means of HR-ICPMS is presented, optimized and established as method

  14. Precise Isotope ratio and multielement determination in prehistoric and historic human skeletal remains by HR-ICPMS - a novel application to shed light onto anthropological and archaeological questions

    International Nuclear Information System (INIS)

    Watkins, M.

    2000-12-01

    The primary aim of the presented work was the analytical setup for fast (including high sample throughput for statistical evaluation), precise and accurate measurement of strontium isotope ratios using HR-ICPMS (high-resolution inductively coupled plasma mass spectrometry) and their application to ancient human skeletal remains from different localities for the reconstruction of migration processes. Soils and plants are in isotopic equilibrium with local source rock and show therefore the same isotopic ratios for strontium (87Sr/86Sr). Dietary strontium incorporation varies for different body materials (teeth, muscle, bone, etc.) and repository periods depend on the different strontium turnover rates. Accordingly, strontium isotope analysis can provide important data for studying human or animal migration and mobility. An important issue will be addressed: the problem of strontium isotope ratio measurement reliability and the problem of post-mortem alterations. Thus a basic part of this interdisciplinary project is dealing with the systematic evaluation of diagenetic changes of the microstructure in human bone samples - including sample uptake and preparation. Different invasive histological techniques will be applied for further clarification. Newly developed chemical methods give us the opportunity to obtain details on ancient population mobility also in skeletal series of extreme fragmentary character, which usually restricts the macro-morphological approach. Since it is evident that strontium in teeth is only incorporated during childhood whereas strontium uptake in bones is constant, an intra-individual comparison of bone and teeth samples will answer the question whether teeth are indeed 'archives of the childhood'. The introduction of an analytical system allowing online matrix separation by High Performance Ion Chromatography (HPIC) and subsequent measurement of strontium isotope ratios by means of HR-ICPMS is presented, optimized and established as method

  15. Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells.

    Science.gov (United States)

    Wang, Rui; Kozhaya, Lina; Mercer, Frances; Khaitan, Alka; Fujii, Hodaka; Unutmaz, Derya

    2009-08-11

    The molecules that define human regulatory T cells (Tregs) phenotypically and functionally remain to be fully characterized. We recently showed that activated human Tregs express mRNA for a transmembrane protein called glycoprotein A repetitions predominant (GARP, or LRRC32). Here, using a GARP-specific mAb, we demonstrate that expression of GARP on activated Tregs correlates with their suppressive capacity. However, GARP was not induced on T cells activated in the presence of TGFbeta, which expressed high levels of FOXP3 and lacked suppressive function. Ectopic expression of FOXP3 in conventional T cells was also insufficient for induction of GARP expression in most donors. Functionally, silencing GARP in Tregs only moderately attenuated their suppressive activity. CD25+ T cells sorted for high GARP expression displayed more potent suppressive activity compared with CD25+GARP- cells. Remarkably, CD25+GARP- T cells expanded in culture contained 3-5 fold higher IL-17-secreting cells compared with either CD25+GARP+ or CD25-GARP- cells, suggesting that high GARP expression can potentially discriminate Tregs from those that have switched to Th17 lineage. We also determined whether GARP expression correlates with FOXP3-expressing T cells in human immunodeficiency virus (HIV) -infected subjects. A subset of HIV+ individuals with high percentages of FOXP3+ T cells did not show proportionate increase in GARP+ T cells. This finding suggests that higher FOXP3 levels observed in these HIV+ individuals is possibly due to immune activation rather than to an increase in Tregs. Our findings highlight the significance of GARP both in dissecting duality of Treg/Th17 cell differentiation and as a marker to identify bona fide Tregs during diseases with chronic immune activation.

  16. Anthropological and palaeopathological analysis of the human remains from three "Tombs of the Nobles" of the necropolis of Thebes-west, upper Egypt.

    Science.gov (United States)

    Nerlich, A; Zink, A; Hagedorn, H G; Szeimies, U; Weyss, C

    2000-12-01

    During several recent excavation campaigns at the necropolis of Sheikh-Abd-el-Gurna, Thebes-West, Upper Egypt, we investigated the human remains of three "Tombs of the Nobles" totalling at least 273 individuals. The investigation covered the human material (skeletons and mummy residues) from the tombs TT-84, TT-85 and TT-95. These tombs had been built in the New Kingdom (approx. 1500-1000 B.C.) and used until the Late period (up to 330 BC). All samples were analyzed macroscopically, isolated findings were further investigated by endoscopic and radiological techniques. The at least 273 individuals covered an age range from newborns to senile individuals with a main age of death between 20 and 40 years of age. The rate of infants and subadults was at 20.2% of all individuals and there was a slight male predominance comprising 54.5% of the adults. In this population a fairly high rate of pathological lesions was seen. Thus, dental conditions generally were poor with a high degree of dental abrasion, an also high rate of carious dental lesions (affecting between 13.8% and 27.7% of the yaws) and consequently a significant number of dental abscesses (mean 15.9%). Residues of trauma were observed in a considerable number of individuals ranging between 12.3% and 22.6% depending on the burial place (mean 15.8%). Inflammatory bone reactions (except the dental abscesses) were present to variable extent, in some locations ranging up to 6.8% of the cases (mean 5.1%). In addition, we noted several cases showing cribra orbitalia (mean 29.2%) and porotic hyperostosis (15.4% of cases), mild to severe osteopenia (7.5%) and in several cases subperiosteal new bone formation suggestive of chronic vitamin D-deficiency ("scurvy") (9.5%). The data support the notion of a significant impairment of living conditions in a high number of individuals. The rates of osteoarthrotic joint alterations were considerably variable depending on the burial places (between 1.9% and 18.5%) providing

  17. Genome-wide analysis identifies 12 loci influencing human reproductive behavior

    DEFF Research Database (Denmark)

    Barban, Nicola; Jansen, Rick; de Vlaming, Ronald

    2016-01-01

    The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the under......The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified...

  18. Genome wide association study identifies KCNMA1 contributing to human obesity

    DEFF Research Database (Denmark)

    Jiao, Hong; Arner, Peter; Hoffstedt, Johan

    2011-01-01

    Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population....... Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity....

  19. Genome-wide analysis identifies 12 loci influencing human reproductive behavior

    NARCIS (Netherlands)

    Barban, Nicola; Jansen, Rick; de Vlaming, Ronald; Vaez, Ahmad; Mandemakers, Jornt J; Tropf, Felix C; Shen, Xia; Wilson, James F; Chasman, Daniel I; Nolte, Ilja M; Tragante, Vinicius; van der Laan, Sander W; Perry, John R B; Kong, Augustine; Ahluwalia, Tarunveer S; Albrecht, Eva; Yerges-Armstrong, Laura; Atzmon, Gil; Auro, Kirsi; Ayers, Kristin; Bakshi, Andrew; Ben-Avraham, Danny; Berger, Klaus; Bergman, Aviv; Bertram, Lars; Bielak, Lawrence F; Bjornsdottir, Gyda; Bonder, Marc Jan; Broer, Linda; Bui, Minh; Barbieri, Caterina; Cavadino, Alana; Chavarro, Jorge E; Turman, Constance; Concas, Maria Pina; Cordell, Heather J; Davies, Gail; Eibich, Peter; Eriksson, Nicholas; Esko, Tõnu; Eriksson, Joel; Falahi, Fahimeh; Felix, Janine F; Fontana, Mark Alan; Franke, Lude; Gandin, Ilaria; Gaskins, Audrey J; Gieger, Christian; Gunderson, Erica P; Guo, Xiuqing; Hayward, Caroline; He, Chunyan; Hofer, Edith; Huang, Hongyan; Joshi, Peter K; Kanoni, Stavroula; Karlsson, Robert; Kiechl, Stefan; Kifley, Annette; Kluttig, Alexander; Kraft, Peter; Lagou, Vasiliki; Lecoeur, Cecile; Lahti, Jari; Li-Gao, Ruifang; Lind, Penelope A; Liu, Tian; Makalic, Enes; Mamasoula, Crysovalanto; Matteson, Lindsay; Mbarek, Hamdi; McArdle, Patrick F; McMahon, George; Meddens, S Fleur W; Mihailov, Evelin; Miller, Mike; Missmer, Stacey A; Monnereau, Claire; van der Most, Peter J; Myhre, Ronny; Nalls, Mike A; Nutile, Teresa; Kalafati, Ioanna Panagiota; Porcu, Eleonora; Prokopenko, Inga; Rajan, Kumar B; Rich-Edwards, Janet; Rietveld, Cornelius A; Robino, Antonietta; Rose, Lynda M; Rueedi, Rico; Ryan, Kathleen A; Saba, Yasaman; Schmidt, Daniel; Smith, Jennifer A; Stolk, Lisette; Streeten, Elizabeth; Tönjes, Anke; Thorleifsson, Gudmar; Ulivi, Sheila; Wedenoja, Juho; Wellmann, Juergen; Willeit, Peter; Yao, Jie; Yengo, Loic; Zhao, Jing Hua; Zhao, Wei; Zhernakova, Daria V; Amin, Najaf; Andrews, Howard; Balkau, Beverley; Barzilai, Nir; Bergmann, Sven; Biino, Ginevra; Bisgaard, Hans; Bønnelykke, Klaus; Boomsma, Dorret I; Buring, Julie E; Campbell, Harry; Cappellani, Stefania; Ciullo, Marina; Cox, Simon R; Cucca, Francesco; Toniolo, Daniela; Davey-Smith, George; Deary, Ian J; Dedoussis, George; Deloukas, Panos; van Duijn, Cornelia M; de Geus, Eco J C; Eriksson, Johan G; Evans, Denis A; Faul, Jessica D; Sala, Cinzia Felicita; Froguel, Philippe; Gasparini, Paolo; Girotto, Giorgia; Grabe, Hans-Jörgen; Greiser, Karin Halina; Groenen, Patrick J F; de Haan, Hugoline G; Haerting, Johannes; Harris, Tamara B; Heath, Andrew C; Heikkilä, Kauko; Hofman, Albert; Homuth, Georg; Holliday, Elizabeth G; Hopper, John; Hyppönen, Elina; Jacobsson, Bo; Jaddoe, Vincent W V; Johannesson, Magnus; Jugessur, Astanand; Kähönen, Mika; Kajantie, Eero; Kardia, Sharon L R; Keavney, Bernard; Kolcic, Ivana; Koponen, Päivikki; Kovacs, Peter; Kronenberg, Florian; Kutalik, Zoltan; La Bianca, Martina; Lachance, Genevieve; Iacono, William G; Lai, Sandra; Lehtimäki, Terho; Liewald, David C; Lindgren, Cecilia M; Liu, Yongmei; Luben, Robert; Lucht, Michael; Luoto, Riitta; Magnus, Per; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; McQuillan, Ruth; Medland, Sarah E; Meisinger, Christa; Mellström, Dan; Metspalu, Andres; Traglia, Michela; Milani, Lili; Mitchell, Paul; Montgomery, Grant W; Mook-Kanamori, Dennis; de Mutsert, Renée; Nohr, Ellen A; Ohlsson, Claes; Olsen, Jørn; Ong, Ken K; Paternoster, Lavinia; Pattie, Alison; Penninx, Brenda W J H; Perola, Markus; Peyser, Patricia A; Pirastu, Mario; Polasek, Ozren; Power, Chris; Kaprio, Jaakko; Raffel, Leslie J; Räikkönen, Katri; Raitakari, Olli; Ridker, Paul M; Ring, Susan M; Roll, Kathryn; Rudan, Igor; Ruggiero, Daniela; Rujescu, Dan; Salomaa, Veikko; Schlessinger, David; Schmidt, Helena; Schmidt, Reinhold; Schupf, Nicole; Smit, Johannes; Sorice, Rossella; Spector, Tim D; Starr, John M; Stöckl, Doris; Strauch, Konstantin; Stumvoll, Michael; Swertz, Morris A; Thorsteinsdottir, Unnur; Thurik, A Roy; Timpson, Nicholas J; Tung, Joyce Y; Uitterlinden, André G; Vaccargiu, Simona; Viikari, Jorma; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Vuckovic, Dragana; Waage, Johannes; Wagner, Gert G; Wang, Jie Jin; Wareham, Nicholas J; Weir, David R; Willemsen, Gonneke; Willeit, Johann; Wright, Alan F; Zondervan, Krina T; Stefansson, Kari; Krueger, Robert F; Lee, James J; Benjamin, Daniel J; Cesarini, David; Koellinger, Philipp D; den Hoed, Marcel; Snieder, Harold; Mills, Melinda C

    2016-01-01

    The genetic architecture of human reproductive behavior age at first birth (AFB) and number of children ever born (NEB) has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the

  20. Genome-wide analysis identifies 12 loci influencing human reproductive behavior

    NARCIS (Netherlands)

    Barban, Nicola; Jansen, Rick; De Vlaming, Ronald; Vaez, Ahmad; Mandemakers, Jornt J.; Tropf, Felix C.; Shen, Xia; Wilson, James F.; Chasman, Daniel I.; Nolte, Ilja M.; Tragante, Vinicius; Van Der Laan, Sander W.; Perry, John R B; Kong, Augustine; Ahluwalia, Tarunveer S.; Albrecht, Eva; Yerges-Armstrong, Laura; Atzmon, Gil; Auro, Kirsi; Ayers, Kristin; Bakshi, Andrew; Ben-Avraham, Danny; Berger, Klaus; Bergman, Aviv; Bertram, Lars; Bielak, Lawrence F.; Bjornsdottir, Gyda; Bonder, Marc Jan; Broer, Linda; Bui, Minh; Barbieri, Caterina; Cavadino, Alana; Chavarro, Jorge E.; Turman, Constance; Concas, Maria Pina; Cordell, Heather J.; Davies, Gail; Eibich, Peter; Eriksson, Nicholas; Esko, Tõnu; Eriksson, Joel; Falahi, Fahimeh; Felix, Janine F.; Fontana, Mark Alan; Franke, Lude; Gandin, Ilaria; Gaskins, Audrey J.; Gieger, Christian; Gunderson, Erica P.; Guo, Xiuqing; Hayward, Caroline; He, Chunyan; Hofer, Edith; Huang, Hongyan; Joshi, Peter K.; Kanoni, Stavroula; Karlsson, Robert; Kiechl, Stefan; Kifley, Annette; Kluttig, Alexander; Kraft, Peter; Lagou, Vasiliki; Lecoeur, Cecile; Lahti, Jari; Li-Gao, Ruifang; Lind, Penelope A.; Liu, Tian; Makalic, Enes; Mamasoula, Crysovalanto; Matteson, Lindsay; Mbarek, Hamdi; McArdle, Patrick F.; McMahon, George; Meddens, S. Fleur W; Mihailov, Evelin; Miller, Mike; Missmer, Stacey A.; Monnereau, Claire; Van Der Most, Peter J.; Myhre, Ronny; Nalls, Mike A.; Nutile, Teresa; Kalafati, Ioanna Panagiota; Porcu, Eleonora; Prokopenko, Inga; Rajan, Kumar B.; Rich-Edwards, Janet; Rietveld, Cornelius A.; Robino, Antonietta; Rose, Lynda M.; Rueedi, Rico; Ryan, Kathleen A.; Saba, Yasaman; Schmidt, Daniel; Smith, Jennifer A.; Stolk, Lisette; Streeten, Elizabeth; Tönjes, Anke; Thorleifsson, Gudmar; Ulivi, Sheila; Wedenoja, Juho; Wellmann, Juergen; Willeit, Peter; Yao, Jie; Yengo, Loic; Zhao, Jing Hua; Zhao, Wei; Zhernakova, Daria V.; Amin, Najaf; Andrews, Howard; Balkau, Beverley; Barzilai, Nir; Bergmann, Sven; Biino, Ginevra; Bisgaard, Hans; Bønnelykke, Klaus; Boomsma, Dorret I.; Buring, Julie E.; Campbell, Harry; Cappellani, Stefania; Ciullo, Marina; Cox, Simon R.; Cucca, Francesco; Toniolo, Daniela; Davey-Smith, George; Deary, Ian J.; Dedoussis, George; Deloukas, Panos; Van Duijn, Cornelia M.; De Geus, Eco J C; Eriksson, Johan G.; Evans, Denis A.; Faul, Jessica D.; Sala, Cinzia Felicita; Froguel, Philippe; Gasparini, Paolo; Girotto, Giorgia; Grabe, Hans Jörgen; Greiser, Karin Halina; Groenen, Patrick J F; De Haan, Hugoline G.; Haerting, Johannes; Harris, Tamara B.; Heath, Andrew C.; Heikkilä, Kauko; Hofman, Albert; Homuth, Georg; Holliday, Elizabeth G.; Hopper, John; Hyppönen, Elina; Jacobsson, Bo; Jaddoe, Vincent W V; Johannesson, Magnus; Jugessur, Astanand; Kähönen, Mika; Kajantie, Eero; Kardia, Sharon L R; Keavney, Bernard; Kolcic, Ivana; Koponen, Päivikki; Kovacs, Peter; Kronenberg, Florian; Kutalik, Zoltan; La Bianca, Martina; Lachance, Genevieve; Iacono, William G.; Lai, Sandra; Lehtimäki, Terho; Liewald, David C.; Lindgren, Cecilia M.; Liu, Yongmei; Luben, Robert; Lucht, Michael; Luoto, Riitta; Magnus, Per; Magnusson, Patrikke; Martin, Nicholas G.; McGue, Matt; McQuillan, Ruth; Medland, Sarah E.; Meisinger, Christa; Mellström, Dan; Metspalu, Andres; Traglia, Michela; Milani, Lili; Mitchell, Paul; Montgomery, Grant W.; Mook-Kanamori, Dennis; De Mutsert, Renée; Nohr, Ellen A.; Ohlsson, Claes; Olsen, Jørn; Ong, Ken K.; Paternoster, Lavinia; Pattie, Alison; Penninx, Brenda W J H; Perola, Markus; Peyser, Patricia A.; Pirastu, Mario; Polasek, Ozren; Power, Chris; Kaprio, Jaakko; Raffel, Leslie J.; Räikkönen, Katri; Raitakari, Olli; Ridker, Paul M.; Ring, Susan M.; Roll, Kathryn; Rudan, Igor; Ruggiero, Daniela; Rujescu, Dan; Salomaa, Veikko; Schlessinger, David; Schmidt, Helena; Schmidt, Reinhold; Schupf, Nicole; Smit, Johannes; Sorice, Rossella; Spector, Tim D.; Starr, John M.; Stöckl, Doris; Strauch, Konstantin; Stumvoll, Michael; Swertz, Morris A.; Thorsteinsdottir, Unnur; Roy Thurik, A.; Timpson, Nicholas J.; Tung, Joyce Y.; Uitterlinden, André G.; Vaccargiu, Simona; Viikari, Jorma; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Vuckovic, Dragana; Waage, Johannes; Wagner, Gert G.; Wang, Jie Jin; Wareham, Nicholas J.; Weir, David R.; Willemsen, Gonneke; Willeit, Johann; Wright, Alan F.; Zondervan, Krina T.; Stefansson, Kari; Krueger, Robert F.; Lee, James J.; Benjamin, Daniel J.; Cesarini, David; Koellinger, Philipp D.; Den Hoed, Marcel; Snieder, Harold; Mills, Melinda C.

    2016-01-01

    The genetic architecture of human reproductive behavior - age at first birth (AFB) and number of children ever born (NEB) - has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the

  1. Genome-wide analysis identifies 12 loci influencing human reproductive behavior

    NARCIS (Netherlands)

    Barban, Nicola; Jansen, Rick; Vlaming, de Ronald; Vaez, Ahmad; Mandemakers, Jornt J.; Tropf, Felix C.; Shen, Xia; Wilson, James F.; Chasman, Daniel I.; Nolte, Ilja M.; Tragante, Vinicius; Laan, van der Sander W.; Perry, John R.B.; Kong, Augustine; Ahluwalia, Tarunveer S.; Albrecht, Eva; Yerges-Armstrong, Laura; Atzmon, Gil; Auro, Kirsi; Ayers, Kristin; Bakshi, Andrew; Ben-Avraham, Danny; Berger, Klaus; Bergman, Aviv; Bertram, Lars; Bielak, Lawrence F.; Bjornsdottir, Gyda; Bonder, Marc Jan; Broer, Linda; Bui, Minh; Barbieri, Caterina; Cavadino, Alana; Chavarro, Jorge E.; Turman, Constance; Concas, Maria Pina; Cordell, Heather J.; Davies, Gail; Eibich, Peter; Eriksson, Nicholas; Esko, Tõnu; Eriksson, Joel; Falahi, Fahimeh; Felix, Janine F.; Fontana, Mark Alan; Franke, Lude; Gandin, Ilaria; Gaskins, Audrey J.; Gieger, Christian; Gunderson, Erica P.; Guo, Xiuqing; Hayward, Caroline; He, Chunyan; Hofer, Edith; Huang, Hongyan; Joshi, Peter K.; Kanoni, Stavroula; Karlsson, Robert; Kiechl, Stefan; Kifley, Annette; Kluttig, Alexander; Kraft, Peter; Lagou, Vasiliki; Lecoeur, Cecile; Lahti, Jari; Li-Gao, Ruifang; Lind, Penelope A.; Liu, Tian; Makalic, Enes; Mamasoula, Crysovalanto; Matteson, Lindsay; Mbarek, Hamdi; McArdle, Patrick F.; McMahon, George; Meddens, S.F.W.; Mihailov, Evelin; Miller, Mike; Missmer, Stacey A.; Monnereau, Claire; Most, van der Peter J.; Myhre, Ronny; Nalls, Mike A.; Nutile, Teresa; Kalafati, Ioanna Panagiota; Porcu, Eleonora; Prokopenko, Inga; Rajan, Kumar B.; Rich-Edwards, Janet; Rietveld, Cornelius A.; Robino, Antonietta; Rose, Lynda M.; Rueedi, Rico; Ryan, Kathleen A.; Saba, Yasaman; Schmidt, Daniel; Smith, Jennifer A.; Stolk, Lisette; Streeten, Elizabeth; Tönjes, Anke; Thorleifsson, Gudmar; Ulivi, Sheila; Wedenoja, Juho; Wellmann, Juergen; Willeit, Peter; Yao, Jie; Yengo, Loic; Zhao, Jing Hua; Zhao, Wei; Zhernakova, Daria V.; Amin, Najaf; Andrews, Howard; Balkau, Beverley; Barzilai, Nir; Bergmann, Sven; Biino, Ginevra; Bisgaard, Hans; Bønnelykke, Klaus; Boomsma, Dorret I.; Buring, Julie E.; Campbell, Harry; Cappellani, Stefania; Ciullo, Marina; Cox, Simon R.; Cucca, Francesco; Toniolo, Daniela; Davey-Smith, George; Deary, Ian J.; Dedoussis, George; Deloukas, Panos; Duijn, van Cornelia M.; Geus, de Eco J.C.; Eriksson, Johan G.; Evans, Denis A.; Faul, Jessica D.; Sala, Cinzia Felicita; Froguel, Philippe; Gasparini, Paolo; Girotto, Giorgia; Grabe, Hans-Jörgen; Greiser, Karin Halina; Groenen, Patrick J.F.; Haan, de Hugoline G.; Haerting, Johannes; Harris, Tamara B.; Heath, Andrew C.; Heikkilä, Kauko; Hofman, Albert; Homuth, Georg; Holliday, Elizabeth G.; Hopper, John; Hyppönen, Elina; Jacobsson, Bo; Jaddoe, Vincent W.V.; Johannesson, Magnus; Jugessur, Astanand; Kähönen, Mika; Kajantie, Eero; Kardia, Sharon L.R.; Keavney, Bernard; Kolcic, Ivana; Koponen, Päivikki; Kovacs, Peter; Kronenberg, Florian; Kutalik, Zoltan; Bianca, la Martina; Lachance, Genevieve; Iacono, William G.; Lai, Sandra; Lehtimäki, Terho; Liewald, David C.; Lindgren, Cecilia M.; Liu, Yongmei; Luben, Robert; Lucht, Michael; Luoto, Riitta; Magnus, Per; Magnusson, Patrik K.E.; Martin, Nicholas G.; McGue, Matt; McQuillan, Ruth; Medland, Sarah E.; Meisinger, Christa; Mellström, Dan; Metspalu, Andres; Traglia, Michela; Milani, Lili; Mitchell, Paul; Montgomery, Grant W.; Mook-Kanamori, Dennis; Mutsert, de Renée; Nohr, Ellen A.; Ohlsson, Claes; Olsen, Jørn; Ong, Ken K.; Paternoster, Lavinia; Pattie, Alison; Penninx, Brenda W.J.H.; Perola, Markus; Peyser, Patricia A.; Pirastu, Mario; Polasek, Ozren; Power, Chris; Kaprio, Jaakko; Raffel, Leslie J.; Räikkönen, Katri; Raitakari, Olli; Ridker, Paul M.; Ring, Susan M.; Roll, Kathryn; Rudan, Igor; Ruggiero, Daniela; Rujescu, Dan; Salomaa, Veikko; Schlessinger, David; Schmidt, Helena; Schmidt, Reinhold; Schupf, Nicole; Smit, Johannes; Sorice, Rossella; Spector, Tim D.; Starr, John M.; Stöckl, Doris; Strauch, Konstantin; Stumvoll, Michael; Swertz, Morris A.; Thorsteinsdottir, Unnur; Thurik, A.R.; Timpson, Nicholas J.; Tung, Joyce Y.; Uitterlinden, André G.; Vaccargiu, Simona; Viikari, Jorma; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Vuckovic, Dragana; Waage, Johannes; Wagner, Gert G.; Wang, Jie Jin; Wareham, Nicholas J.; Weir, David R.; Willemsen, Gonneke; Willeit, Johann; Wright, Alan F.; Zondervan, Krina T.; Stefansson, Kari; Krueger, Robert F.; Lee, James J.; Benjamin, Daniel J.; Cesarini, David; Koellinger, Philipp D.; Hoed, den Marcel; Snieder, Harold; Mills, Melinda C.

    2016-01-01

    The genetic architecture of human reproductive behavior—age at first birth (AFB) and number of children ever born (NEB)—has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the

  2. Identifying and managing conflicts between forest conservation and other human interests in Europe

    NARCIS (Netherlands)

    Niemela, J.; Young, J.; Alard, D.; Askasibar, M.; Henle, K.; Johnson, R.; Kurttila, M.; Larsson, T.B.; Matouch, S.; Nowicki, P.L.; Paiva, R.Q.; Portoghesi, L.; Smulders, M.J.M.; Stevenson, A.; Tartes, U.; Watt, A.

    2005-01-01

    In this paper, circumstances where various human activities and interests clash with the conservation of forest biodiversity are examined, with particular focus on the drivers behind the conflicts. After identifying past and current human-related threats potentially leading to conflicts in forests,

  3. A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets

    DEFF Research Database (Denmark)

    Taneera, Jalal; Lang, Stefan; Sharma, Amitabh

    2012-01-01

    Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors. Using 48 genes located near T2D risk variants, we identified ...

  4. Establishing a minimum postmortem interval of human remains in an advanced state of skeletonization using the growth rate of bryophytes and plant roots.

    Science.gov (United States)

    Cardoso, H F V; Santos, A; Dias, R; Garcia, C; Pinto, M; Sérgio, C; Magalhães, T

    2010-09-01

    This paper illustrates the usefulness and efficiency of botanical evidence in establishing a minimum postmortem interval (PMI). The case under analysis refers to the remains of an adult male in an advanced state of skeletonization recovered from a wooded area in northern Portugal. The skeleton showed several taphonomical changes, which included the presence of green algae, bryophytes, and growing shrub roots in, around, and through the remains. By determining the age of both the bryophytes and shrub roots, it was concluded that the minimum amount of time elapsed since death was 3 years, to which several months or a few years have to be added to account for the complete decomposition of the remains. The disappearance of the presumptive individual had occurred 6 years before and is fully consistent with the estimate of the PMI. This report illustrates a novel use of bryophytes in a forensic setting.

  5. Using reporter gene assays to identify cis regulatory differences between humans and chimpanzees.

    Science.gov (United States)

    Chabot, Adrien; Shrit, Ralla A; Blekhman, Ran; Gilad, Yoav

    2007-08-01

    Most phenotypic differences between human and chimpanzee are likely to result from differences in gene regulation, rather than changes to protein-coding regions. To date, however, only a handful of human-chimpanzee nucleotide differences leading to changes in gene regulation have been identified. To hone in on differences in regulatory elements between human and chimpanzee, we focused on 10 genes that were previously found to be differentially expressed between the two species. We then designed reporter gene assays for the putative human and chimpanzee promoters of the 10 genes. Of seven promoters that we found to be active in human liver cell lines, human and chimpanzee promoters had significantly different activity in four cases, three of which recapitulated the gene expression difference seen in the microarray experiment. For these three genes, we were therefore able to demonstrate that a change in cis influences expression differences between humans and chimpanzees. Moreover, using site-directed mutagenesis on one construct, the promoter for the DDA3 gene, we were able to identify three nucleotides that together lead to a cis regulatory difference between the species. High-throughput application of this approach can provide a map of regulatory element differences between humans and our close evolutionary relatives.

  6. More on contamination: the use of asymmetric molecular behavior to identify authentic ancient human DNA

    DEFF Research Database (Denmark)

    Malmström, Helena; Svensson, Emma M; Gilbert, M Thomas P

    2007-01-01

    concerning the authenticity of such data. Although several methods have been developed to the purpose of authenticating ancient DNA (aDNA) results, while they are useful in faunal research, most of the methods have proven complicated to apply to ancient human DNA. Here, we investigate in detail...... the reliability of one of the proposed criteria, that of appropriate molecular behavior. Using real-time polymerase chain reaction (PCR) and pyrosequencing, we have quantified the relative levels of authentic aDNA and contaminant human DNA sequences recovered from archaeological dog and cattle remains. In doing...

  7. Objective Model Selection for Identifying the Human Feedforward Response in Manual Control

    OpenAIRE

    Drop, F.M.; Pool, D.M.; van Paassen, M.M.; Mulder, M.; Bülthoff, Heinrich H.

    2017-01-01

    Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification proce...

  8. Identifying pathogenicity of human variants via paralog-based yeast complementation.

    Directory of Open Access Journals (Sweden)

    Fan Yang

    2017-05-01

    Full Text Available To better understand the health implications of personal genomes, we now face a largely unmet challenge to identify functional variants within disease-associated genes. Functional variants can be identified by trans-species complementation, e.g., by failure to rescue a yeast strain bearing a mutation in an orthologous human gene. Although orthologous complementation assays are powerful predictors of pathogenic variation, they are available for only a few percent of human disease genes. Here we systematically examine the question of whether complementation assays based on paralogy relationships can expand the number of human disease genes with functional variant detection assays. We tested over 1,000 paralogous human-yeast gene pairs for complementation, yielding 34 complementation relationships, of which 33 (97% were novel. We found that paralog-based assays identified disease variants with success on par with that of orthology-based assays. Combining all homology-based assay results, we found that complementation can often identify pathogenic variants outside the homologous sequence region, presumably because of global effects on protein folding or stability. Within our search space, paralogy-based complementation more than doubled the number of human disease genes with a yeast-based complementation assay for disease variation.

  9. Proteomic profiling of human plasma exosomes identifies PPARγ as an exosome-associated protein

    International Nuclear Information System (INIS)

    Looze, Christopher; Yui, David; Leung, Lester; Ingham, Matthew; Kaler, Maryann; Yao, Xianglan; Wu, Wells W.; Shen Rongfong; Daniels, Mathew P.; Levine, Stewart J.

    2009-01-01

    Exosomes are nanovesicles that are released from cells as a mechanism of cell-free intercellular communication. Only a limited number of proteins have been identified from the plasma exosome proteome. Here, we developed a multi-step fractionation scheme incorporating gel exclusion chromatography, rate zonal centrifugation through continuous sucrose gradients, and high-speed centrifugation to purify exosomes from human plasma. Exosome-associated proteins were separated by SDS-PAGE and 66 proteins were identified by LC-MS/MS, which included both cellular and extracellular proteins. Furthermore, we identified and characterized peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor that regulates adipocyte differentiation and proliferation, as well as immune and inflammatory cell functions, as a novel component of plasma-derived exosomes. Given the important role of exosomes as intercellular messengers, the discovery of PPARγ as a component of human plasma exosomes identifies a potential new pathway for the paracrine transfer of nuclear receptors.

  10. Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis

    Science.gov (United States)

    Swindell, William R.; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P.; Voorhees, John J.; Elder, James T.; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P.; DiGiovanni, John; Pittelkow, Mark R.; Ward, Nicole L.; Gudjonsson, Johann E.

    2011-01-01

    Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. PMID:21483750

  11. Learning to Identify Local Flora with Human Feedback (Author’s Manuscript)

    Science.gov (United States)

    2014-06-23

    cally tag images with species names of flora or fauna to sup- port content-based retrieval [10]. Detecting and identifying species could help to infer...Learning to Identify Local Flora with Human Feedback Stefan Lee and David Crandall School of Informatics and Computing Indiana University {steflee...applications that use consumer pho- tos to track the distribution of natural phenomena [8]. But flora identification is a very difficult problem, both

  12. Filling the gap. Human cranial remains from Gombore II (Melka Kunture, Ethiopia; ca. 850 ka) and the origin of Homo heidelbergensis.

    Science.gov (United States)

    Profico, Antonio; Di Vincenzo, Fabio; Gagliardi, Lorenza; Piperno, Marcello; Manzi, Giorgio

    2016-06-20

    African archaic humans dated to around 1,0 Ma share morphological affinities with Homo ergaster and appear distinct in cranio-dental morphology from those of the Middle Pleistocene that are referred to Homo heidelbergensis. This observation suggests a taxonomic and phylogenetic discontinuity in Africa that ranges across the Matuyama/Brunhes reversal (780 ka). Yet, the fossil record between roughly 900 and 600 ka is notoriously poor. In this context, the Early Stone Age site of Gombore II, in the Melka Kunture formation (Upper Awash, Ethiopia), provides a privileged case-study. In the Acheulean layer of Gombore II, somewhat more recent than 875 ±10 ka, two large cranial fragments were discovered in 1973 and 1975 respectively: a partial left parietal (Melka Kunture 1) and a right portion of the frontal bone (Melka Kunture 2), which probably belonged to the same cranium. We present here the first detailed description and computer-assisted reconstruction of the morphology of the cranial vault pertaining to these fossil fragments. Our analysis suggest that the human fossil specimen from Gombore II fills a phenetic gap between Homo ergaster and Homo heidelbergensis. This appears in agreement with the chronology of such a partial cranial vault, which therefore represents at present one of the best available candidates (if any) for the origin of Homo heidelbergensis in Africa.

  13. Metastasis-related plasma membrane proteins of human breast cancer cells identified by comparative quantitative mass spectrometry

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Lund, Rikke; Hansen, Helle V

    2009-01-01

    The spread of cancer cells from a primary tumor to form metastasis at distant sites is a complex multi-step process. The cancer cell proteins, and plasma membrane proteins in particular, involved in this process are poorly defined and a study of the very early events of the metastatic process using...... clinical samples or in vitro assays is not feasible. We have used a unique model system consisting of two isogenic human breast cancer cell lines that are equally tumorigenic in mice, but while one gives rise to metastasis, the other disseminates single cells that remain dormant at distant organs. Membrane...... purification and comparative quantitative LC-MS/MS proteomic analysis identified 13 membrane proteins that were expressed at higher levels and 3 that were under-expressed in the metastatic compared to the non-metastatic cell line from a total of 1919 identified protein entries. Among the proteins were ecto-5...

  14. A COUP-TFII Human Embryonic Stem Cell Reporter Line to Identify and Select Atrial Cardiomyocytes

    NARCIS (Netherlands)

    Schwach, Verena; Verkerk, Arie O.; Mol, Mervyn; Monshouwer-Kloots, Jantine J.; Devalla, Harsha D.; Orlova, Valeria V.; Anastassiadis, Konstantinos; Mummery, Christine L.; Davis, Richard P.; Passier, Robert

    2017-01-01

    Reporter cell lines have already proven valuable in identifying, tracking, and purifying cardiac subtypes and progenitors during differentiation of human pluripotent stem cells (hPSCs). We previously showed that chick ovalbumin upstream promoter transcription factor II (COUP-TFII) is highly enriched

  15. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Boomsma, Wouter Krogh; Nielsen, Sofie Vincents; Lindorff-Larsen, Kresten

    2016-01-01

    conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology...

  16. The Human Genome Project and Eugenics: Identifying the Impact on Individuals with Mental Retardation.

    Science.gov (United States)

    Kuna, Jason

    2001-01-01

    This article explores the impact of the mapping work of the Human Genome Project on individuals with mental retardation and the negative effects of genetic testing. The potential to identify disabilities and the concept of eugenics are discussed, along with ethical issues surrounding potential genetic therapies. (Contains references.) (CR)

  17. New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes

    DEFF Research Database (Denmark)

    Parker, Brian John; Moltke, Ida; Roth, Adam

    2011-01-01

    a comparative method, EvoFam, for genome-wide identification of families of regulatory RNA structures, based on primary sequence and secondary structure similarity. We apply EvoFam to a 41-way genomic vertebrate alignment. Genome-wide, we identify 220 human, high-confidence families outside protein...

  18. Identifying Victims of Human Trafficking at Hotspots by Focusing on People Smuggled to Europe

    Directory of Open Access Journals (Sweden)

    Matilde Ventrella

    2017-06-01

    Full Text Available Research has shown that smuggling of migrants is associated with human trafficking. Hence, victims of human trafficking amongst smuggled migrants should be identified by EU Member States at hotspots established by the European Commission, to overcome the migrant and refugee crisis. Identified victims should be given a visa and a programme of protection to escape their traffickers. In order to achieve these objectives, research suggests that EU law on migrant smuggling should be amended and the Temporary Protection Directive should be applied to smuggled persons when there is an indication that they may be victims of human trafficking. This approach should be adopted by the EASO in cooperation with police forces investigating smuggling and trafficking at hotspots.

  19. Genome-wide analysis identifies 12 loci influencing human reproductive behavior

    Science.gov (United States)

    Barban, Nicola; Jansen, Rick; de Vlaming, Ronald; Vaez, Ahmad; Mandemakers, Jornt J.; Tropf, Felix C.; Shen, Xia; Wilson, James F.; Chasman, Daniel I.; Nolte, Ilja M.; Tragante, Vinicius; van der Laan, Sander W.; Perry, John R. B.; Kong, Augustine; Ahluwalia, Tarunveer; Albrecht, Eva; Yerges-Armstrong, Laura; Atzmon, Gil; Auro, Kirsi; Ayers, Kristin; Bakshi, Andrew; Ben-Avraham, Danny; Berger, Klaus; Bergman, Aviv; Bertram, Lars; Bielak, Lawrence F.; Bjornsdottir, Gyda; Bonder, Marc Jan; Broer, Linda; Bui, Minh; Barbieri, Caterina; Cavadino, Alana; Chavarro, Jorge E; Turman, Constance; Concas, Maria Pina; Cordell, Heather J.; Davies, Gail; Eibich, Peter; Eriksson, Nicholas; Esko, Tõnu; Eriksson, Joel; Falahi, Fahimeh; Felix, Janine F.; Fontana, Mark Alan; Franke, Lude; Gandin, Ilaria; Gaskins, Audrey J.; Gieger, Christian; Gunderson, Erica P.; Guo, Xiuqing; Hayward, Caroline; He, Chunyan; Hofer, Edith; Huang, Hongyan; Joshi, Peter K.; Kanoni, Stavroula; Karlsson, Robert; Kiechl, Stefan; Kifley, Annette; Kluttig, Alexander; Kraft, Peter; Lagou, Vasiliki; Lecoeur, Cecile; Lahti, Jari; Li-Gao, Ruifang; Lind, Penelope A.; Liu, Tian; Makalic, Enes; Mamasoula, Crysovalanto; Matteson, Lindsay; Mbarek, Hamdi; McArdle, Patrick F.; McMahon, George; Meddens, S. Fleur W.; Mihailov, Evelin; Miller, Mike; Missmer, Stacey A.; Monnereau, Claire; van der Most, Peter J.; Myhre, Ronny; Nalls, Mike A.; Nutile, Teresa; Panagiota, Kalafati Ioanna; Porcu, Eleonora; Prokopenko, Inga; Rajan, Kumar B.; Rich-Edwards, Janet; Rietveld, Cornelius A.; Robino, Antonietta; Rose, Lynda M.; Rueedi, Rico; Ryan, Kathy; Saba, Yasaman; Schmidt, Daniel; Smith, Jennifer A.; Stolk, Lisette; Streeten, Elizabeth; Tonjes, Anke; Thorleifsson, Gudmar; Ulivi, Sheila; Wedenoja, Juho; Wellmann, Juergen; Willeit, Peter; Yao, Jie; Yengo, Loic; Zhao, Jing Hua; Zhao, Wei; Zhernakova, Daria V.; Amin, Najaf; Andrews, Howard; Balkau, Beverley; Barzilai, Nir; Bergmann, Sven; Biino, Ginevra; Bisgaard, Hans; Bønnelykke, Klaus; Boomsma, Dorret I.; Buring, Julie E.; Campbell, Harry; Cappellani, Stefania; Ciullo, Marina; Cox, Simon R.; Cucca, Francesco; Daniela, Toniolo; Davey-Smith, George; Deary, Ian J.; Dedoussis, George; Deloukas, Panos; van Duijn, Cornelia M.; de Geus, Eco JC.; Eriksson, Johan G.; Evans, Denis A.; Faul, Jessica D.; Felicita, Sala Cinzia; Froguel, Philippe; Gasparini, Paolo; Girotto, Giorgia; Grabe, Hans-Jörgen; Greiser, Karin Halina; Groenen, Patrick J.F.; de Haan, Hugoline G.; Haerting, Johannes; Harris, Tamara B.; Heath, Andrew C.; Heikkilä, Kauko; Hofman, Albert; Homuth, Georg; Holliday, Elizabeth G; Hopper, John; Hypponen, Elina; Jacobsson, Bo; Jaddoe, Vincent W. V.; Johannesson, Magnus; Jugessur, Astanand; Kähönen, Mika; Kajantie, Eero; Kardia, Sharon L.R.; Keavney, Bernard; Kolcic, Ivana; Koponen, Päivikki; Kovacs, Peter; Kronenberg, Florian; Kutalik, Zoltan; La Bianca, Martina; Lachance, Genevieve; Iacono, William; Lai, Sandra; Lehtimäki, Terho; Liewald, David C; Lindgren, Cecilia; Liu, Yongmei; Luben, Robert; Lucht, Michael; Luoto, Riitta; Magnus, Per; Magnusson, Patrik K.E.; Martin, Nicholas G.; McGue, Matt; McQuillan, Ruth; Medland, Sarah E.; Meisinger, Christa; Mellström, Dan; Metspalu, Andres; Michela, Traglia; Milani, Lili; Mitchell, Paul; Montgomery, Grant W.; Mook-Kanamori, Dennis; de Mutsert, Renée; Nohr, Ellen A; Ohlsson, Claes; Olsen, Jørn; Ong, Ken K.; Paternoster, Lavinia; Pattie, Alison; Penninx, Brenda WJH; Perola, Markus; Peyser, Patricia A.; Pirastu, Mario; Polasek, Ozren; Power, Chris; Kaprio, Jaakko; Raffel, Leslie J.; Räikkönen, Katri; Raitakari, Olli; Ridker, Paul M.; Ring, Susan M.; Roll, Kathryn; Rudan, Igor; Ruggiero, Daniela; Rujescu, Dan; Salomaa, Veikko; Schlessinger, David; Schmidt, Helena; Schmidt, Reinhold; Schupf, Nicole; Smit, Johannes; Sorice, Rossella; Spector, Tim D.; Starr, John M.; Stöckl, Doris; Strauch, Konstantin; Stumvoll, Michael; Swertz, Morris A.; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tönjes, Anke; Tung, Joyce Y.; Uitterlinden, André G.; Vaccargiu, Simona; Viikari, Jorma; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Vuckovic, Dragana; Waage, Johannes; Wagner, Gert G.; Wang, Jie Jin; Wareham, Nicholas J.; Weir, David R.; Willemsen, Gonneke; Willeit, Johann; Wright, Alan F.; Zondervan, Krina T.; Stefansson, Kari; Krueger, Robert F.; Lee, James J.; Benjamin, Daniel J.; Cesarini, David; Koellinger, Philipp D.; den Hoed, Marcel; Snieder, Harold; Mills, Melinda C.

    2017-01-01

    The genetic architecture of human reproductive behavior – age at first birth (AFB) and number of children ever born (NEB) – has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified and the underlying mechanisms of AFB and NEB are poorly understood. We report the largest genome-wide association study to date of both sexes including 251,151 individuals for AFB and 343,072 for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study, and four additional loci in a gene-based effort. These loci harbor genes that are likely to play a role – either directly or by affecting non-local gene expression – in human reproduction and infertility, thereby increasing our understanding of these complex traits. PMID:27798627

  20. III TALLER DE DISCUSIÓN SOBRE RESTITUCIÓN DE RESTOS HUMANOS DE INTERÉS ARQUEOLÓGICO Y BIOANTROPOLÓGICO / III Discussion Workshop on the Return of Human Remains of Archaeological and Bioanthropological Interest

    Directory of Open Access Journals (Sweden)

    María Luz Endere

    2014-11-01

    Full Text Available En este trabajo se presentan los resultados del III Taller de Discusión sobre Restitución de Restos Humanos de Interés Arqueológico llevado a cabo en Junio de 2013 en la ciudad de Olavarría.   Palabras Clave: restos humanos de origen arqueológico, restitución, etica, práctica profesional   Abstract This paper presents the results of the III Discussion Workshop to discuss human remains restitution of archaeological interest, held in June 2013 in the city of Olavarria.   Keywords: human remains from archaeological contexts, restitution, ethics, professional practice.

  1. The fate of human remains in a maritime context and feasibility for forensic humanitarian action to assist in their recovery and identification.

    Science.gov (United States)

    Ellingham, Sarah Theresa Dorothea; Perich, Pierre; Tidball-Binz, Morris

    2017-10-01

    The number of annual maritime fatalities reported in the Mediterranean has more than doubled in the last two years, a phenomenon closely linked to the increase of migrants attempting to reach Europe via the Mediterranean. The majority of victims reportedly never gets recovered, which in part relates to the fact that the mechanisms and interaction of factors affecting marine taphonomy are still largely not understood. These factors include intrinsic factors such as whether the individual was alive or dead at the time of submergence, the individual's stature and clothing, as well as extrinsic factors such including ambient temperature, currents, water depth, salinity and oxygen levels. This paper provides a compilation of the current literature on factors influencing marine taphonomy, recovery and identification procedures for submerged remains, and discusses the implications for the retrieval and identification of maritime mass fatalities as part of the humanitarian response, specifically humanitarian forensic action, to the consequences of the current migration phenomenon. Copyright © 2017. Published by Elsevier B.V.

  2. A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

    Directory of Open Access Journals (Sweden)

    David G Ashbrook

    2015-07-01

    Full Text Available Bipolar disorder (BD is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium’s bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis.We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1 and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG and TNR influence intercellular signaling in the striatum.

  3. Motor function declines over time in human immunodeficiency virus and is associated with cerebrovascular disease, while HIV-associated neurocognitive disorder remains stable.

    Science.gov (United States)

    M Elicer, Isabel; Byrd, Desiree; Clark, Uraina S; Morgello, Susan; Robinson-Papp, Jessica

    2018-04-25

    HIV-associated neurocognitive disorders (HAND) remain prevalent in the combined antiretroviral therapy (CART) era, especially the milder forms. Despite these milder phenotypes, we have shown that motor abnormalities persist and have quantified them with the HIV Dementia Motor Scale (HDMS). Our objectives were to replicate, in an independent sample, our prior findings that the HDMS is associated with cognitive impairment in HIV, while adding consideration of age-associated comorbidities such as cerebrovascular disease, and to examine the longitudinal trajectories of cognitive and motor dysfunction. We included all participants enrolled in the Manhattan HIV Brain Bank (MHBB) from January 2007 to May 2017 who had complete baseline data (N = 164). MHBB participants undergo standardized longitudinal assessments including documentation of comorbidities and medications, blood work, the HDMS, and neurocognitive testing. We found that motor dysfunction, cognitive impairment, and cerebrovascular disease were significantly associated with each other at baseline. Cerebrovascular disease independently predicted cognitive impairment in a multivariable model. Longitudinal analysis in a subset of 78 participants with ≥ 4 years of follow-up showed a stable cognition but declining motor function. We conclude that the HDMS is a valid measurement of motor dysfunction in HIV-infected patients and is associated with cognitive impairment and the presence of cerebrovascular disease. Cognitive impairment is mild and stable in CART-treated HIV; however, motor function declines over time, which may be related to the accrual of comorbidities such as cerebrovascular disease. Further research should examine the mechanisms underlying motor dysfunction in HIV and its clinical impact.

  4. Identifying human disease genes through cross-species gene mapping of evolutionary conserved processes.

    Directory of Open Access Journals (Sweden)

    Martin Poot

    2011-05-01

    Full Text Available Understanding complex networks that modulate development in humans is hampered by genetic and phenotypic heterogeneity within and between populations. Here we present a method that exploits natural variation in highly diverse mouse genetic reference panels in which genetic and environmental factors can be tightly controlled. The aim of our study is to test a cross-species genetic mapping strategy, which compares data of gene mapping in human patients with functional data obtained by QTL mapping in recombinant inbred mouse strains in order to prioritize human disease candidate genes.We exploit evolutionary conservation of developmental phenotypes to discover gene variants that influence brain development in humans. We studied corpus callosum volume in a recombinant inbred mouse panel (C57BL/6J×DBA/2J, BXD strains using high-field strength MRI technology. We aligned mouse mapping results for this neuro-anatomical phenotype with genetic data from patients with abnormal corpus callosum (ACC development.From the 61 syndromes which involve an ACC, 51 human candidate genes have been identified. Through interval mapping, we identified a single significant QTL on mouse chromosome 7 for corpus callosum volume with a QTL peak located between 25.5 and 26.7 Mb. Comparing the genes in this mouse QTL region with those associated with human syndromes (involving ACC and those covered by copy number variations (CNV yielded a single overlap, namely HNRPU in humans and Hnrpul1 in mice. Further analysis of corpus callosum volume in BXD strains revealed that the corpus callosum was significantly larger in BXD mice with a B genotype at the Hnrpul1 locus than in BXD mice with a D genotype at Hnrpul1 (F = 22.48, p<9.87*10(-5.This approach that exploits highly diverse mouse strains provides an efficient and effective translational bridge to study the etiology of human developmental disorders, such as autism and schizophrenia.

  5. Geographically Modified PageRank Algorithms: Identifying the Spatial Concentration of Human Movement in a Geospatial Network.

    Science.gov (United States)

    Chin, Wei-Chien-Benny; Wen, Tzai-Hung

    2015-01-01

    A network approach, which simplifies geographic settings as a form of nodes and links, emphasizes the connectivity and relationships of spatial features. Topological networks of spatial features are used to explore geographical connectivity and structures. The PageRank algorithm, a network metric, is often used to help identify important locations where people or automobiles concentrate in the geographical literature. However, geographic considerations, including proximity and location attractiveness, are ignored in most network metrics. The objective of the present study is to propose two geographically modified PageRank algorithms-Distance-Decay PageRank (DDPR) and Geographical PageRank (GPR)-that incorporate geographic considerations into PageRank algorithms to identify the spatial concentration of human movement in a geospatial network. Our findings indicate that in both intercity and within-city settings the proposed algorithms more effectively capture the spatial locations where people reside than traditional commonly-used network metrics. In comparing location attractiveness and distance decay, we conclude that the concentration of human movement is largely determined by the distance decay. This implies that geographic proximity remains a key factor in human mobility.

  6. Geographically Modified PageRank Algorithms: Identifying the Spatial Concentration of Human Movement in a Geospatial Network.

    Directory of Open Access Journals (Sweden)

    Wei-Chien-Benny Chin

    Full Text Available A network approach, which simplifies geographic settings as a form of nodes and links, emphasizes the connectivity and relationships of spatial features. Topological networks of spatial features are used to explore geographical connectivity and structures. The PageRank algorithm, a network metric, is often used to help identify important locations where people or automobiles concentrate in the geographical literature. However, geographic considerations, including proximity and location attractiveness, are ignored in most network metrics. The objective of the present study is to propose two geographically modified PageRank algorithms-Distance-Decay PageRank (DDPR and Geographical PageRank (GPR-that incorporate geographic considerations into PageRank algorithms to identify the spatial concentration of human movement in a geospatial network. Our findings indicate that in both intercity and within-city settings the proposed algorithms more effectively capture the spatial locations where people reside than traditional commonly-used network metrics. In comparing location attractiveness and distance decay, we conclude that the concentration of human movement is largely determined by the distance decay. This implies that geographic proximity remains a key factor in human mobility.

  7. Eliminating mother-to-child transmission of the human immunodeficiency virus in sub-Saharan Africa: The journey so far and what remains to be done.

    Science.gov (United States)

    Adetokunboh, Olatunji O; Oluwasanu, Mojisola

    2016-01-01

    This review was carried out to provide a comprehensive overview of efforts toward elimination of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) with respect to progress, challenges, and recommendations in 21 sub-Saharan African priority countries. We reviewed literature published from 2011 to April 2015 using 3 databases; PubMed, Scopus, and Web of Science, as well as the 2014 Global Plan Progress Report. A total of 39 studies were included. Between 2009 and 2013, there was a 43% reduction in new HIV infections, the final MTCT rate was reduced from 28% to 18%, and antiretroviral therapy (ART) coverage increased from 11% to 24%. Challenges included poor adherence to antiretroviral therapy, poor linkage between mother-child pairs and post-natal healthcare services low early infant diagnosis coverage, low pediatric ART coverage, and high unmet needs for contraceptive services. Future recommendations include identification of key barriers, health system strengthening, strengthening community involvement, and international collaboration. There has been significant progress toward eliminating MTCT of HIV, but more effort is still needed. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  8. Objective Model Selection for Identifying the Human Feedforward Response in Manual Control.

    Science.gov (United States)

    Drop, Frank M; Pool, Daan M; van Paassen, Marinus Rene M; Mulder, Max; Bulthoff, Heinrich H

    2018-01-01

    Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification procedure is presented that aims at an objective model selection for identifying the human feedforward response, using linear time-invariant autoregressive with exogenous input models. A new model selection criterion is proposed to decide on the model order (number of parameters) and the presence of feedforward in addition to feedback. For a range of typical control tasks, it is shown by means of Monte Carlo computer simulations that the classical Bayesian information criterion (BIC) leads to selecting models that contain a feedforward path from data generated by a pure feedback model: "false-positive" feedforward detection. To eliminate these false-positives, the modified BIC includes an additional penalty on model complexity. The appropriate weighting is found through computer simulations with a hypothesized HC model prior to performing a tracking experiment. Experimental human-in-the-loop data will be considered in future work. With appropriate weighting, the method correctly identifies the HC dynamics in a wide range of control tasks, without false-positive results.

  9. Identifying community thresholds for lotic benthic diatoms in response to human disturbance.

    Science.gov (United States)

    Tang, Tao; Tang, Ting; Tan, Lu; Gu, Yuan; Jiang, Wanxiang; Cai, Qinghua

    2017-06-23

    Although human disturbance indirectly influences lotic assemblages through modifying physical and chemical conditions, identifying thresholds of human disturbance would provide direct evidence for preventing anthropogenic degradation of biological conditions. In the present study, we used data obtained from tributaries of the Three Gorges Reservoir in China to detect effects of human disturbance on streams and to identify disturbance thresholds for benthic diatoms. Diatom species composition was significantly affected by three in-stream stressors including TP, TN and pH. Diatoms were also influenced by watershed % farmland and natural environmental variables. Considering three in-stream stressors, TP was positively influenced by % farmland and % impervious surface area (ISA). In contrast, TN and pH were principally affected by natural environmental variables. Among measured natural environmental variables, average annual air temperature, average annual precipitation, and topsoil % CaCO 3 , % gravel, and total exchangeable bases had significant effects on study streams. When effects of natural variables were accounted for, substantial compositional changes in diatoms occurred when farmland or ISA land use exceeded 25% or 0.3%, respectively. Our study demonstrated the rationale for identifying thresholds of human disturbance for lotic assemblages and addressed the importance of accounting for effects of natural factors for accurate disturbance thresholds.

  10. Luminol testing in detecting modern human skeletal remains: a test on different types of bone tissue and a caveat for PMI interpretation.

    Science.gov (United States)

    Caudullo, Giorgio; Caruso, Valentina; Cappella, Annalisa; Sguazza, Emanuela; Mazzarelli, Debora; Amadasi, Alberto; Cattaneo, Cristina

    2017-01-01

    When forensic pathologists and anthropologists have to deal with the evaluation of the post-mortem interval (PMI) in skeletal remains, luminol testing is frequently performed as a preliminary screening method. However, the repeatability of this test on the same bone, as well as comparative studies on different bones of the same individual, has never been performed. Therefore, with the aim of investigating the influence that different types of bones may exert on the response to the luminol test, the present study analysed three different skeletal elements (femoral diaphysis, vertebra and cranial vault), gathered from ten recent exhumed skeletons (all with a 20-year PMI). The analysis was performed twice on the same bone after 2 months: the analysis at time 0 concerned the whole bone, whereas the second concerned only a part of the same bone taken during the first test (which already had been broken). The overall results showed different responses, depending on the type of bone and on the integrity of the samples. Negative results at the first analysis (6.6% out of the total of samples) are consistent with what is reported in the literature, whilst at the second analysis, the increase of about 20% of false-negative results highlights that the luminol test ought to be performed with caution in case of broken bones or elements which are taphonomically altered. Results have thus proven that the exposition to environmental agents might result in haemoglobin (Hb) loss, as detected even after only 2 months. The study also focused on the crucial issue of the type of bone subjected to testing, remarking the suitability of the femoral diaphysis (100% of positive responses at the first analysis vs only 18% of false-negative results at the second test, corresponding to 5% of total false-negative results) as opposed to other bone elements that showed a low yield. In particular, the cranial vault gave poor results, with 40% of discrepancy between results from the two analyses

  11. Molecular docking and NMR binding studies to identify novel inhibitors of human phosphomevalonate kinase

    Energy Technology Data Exchange (ETDEWEB)

    Boonsri, Pornthip [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States); Department of Chemistry, NANOTEC Center of Nanotechnology, National Nanotechnology Center, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Neumann, Terrence S.; Olson, Andrew L.; Cai, Sheng [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States); Herdendorf, Timothy J.; Miziorko, Henry M. [Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Hannongbua, Supa [Department of Chemistry, NANOTEC Center of Nanotechnology, National Nanotechnology Center, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Sem, Daniel S., E-mail: daniel.sem@cuw.edu [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Natural and synthetic inhibitors of human phosphomevalonate kinase identified. Black-Right-Pointing-Pointer Virtual screening yielded a hit rate of 15%, with inhibitor K{sub d}'s of 10-60 {mu}M. Black-Right-Pointing-Pointer NMR studies indicate significant protein conformational changes upon binding. -- Abstract: Phosphomevalonate kinase (PMK) phosphorylates mevalonate-5-phosphate (M5P) in the mevalonate pathway, which is the sole source of isoprenoids and steroids in humans. We have identified new PMK inhibitors with virtual screening, using autodock. Promising hits were verified and their affinity measured using NMR-based {sup 1}H-{sup 15}N heteronuclear single quantum coherence (HSQC) chemical shift perturbation and fluorescence titrations. Chemical shift changes were monitored, plotted, and fitted to obtain dissociation constants (K{sub d}). Tight binding compounds with K{sub d}'s ranging from 6-60 {mu}M were identified. These compounds tended to have significant polarity and negative charge, similar to the natural substrates (M5P and ATP). HSQC cross peak changes suggest that binding induces a global conformational change, such as domain closure. Compounds identified in this study serve as chemical genetic probes of human PMK, to explore pharmacology of the mevalonate pathway, as well as starting points for further drug development.

  12. Identifying Human Trafficking Victims on a Psychiatry Inpatient Service: a Case Series.

    Science.gov (United States)

    Nguyen, Phuong T; Lamkin, Joanna; Coverdale, John H; Scott, Samuel; Li, Karen; Gordon, Mollie R

    2018-06-01

    Human trafficking is a serious and prevalent human rights violation that closely intersects with mental health. Limited empirical attention has been paid to the presentations and identification of trafficking victims in psychiatric settings. The primary goal of this paper is to describe the varied presentations of trafficking victims on an urban inpatient psychiatric unit. A literature review was conducted to identify relevant empirical articles to inform our examination of cases. Adult inpatient cases meeting criteria for known or possible human trafficking were systematically identified and illustrative cases were described. Six cases were identified including one male and five females. Two had been labor trafficked and four were suspected or confirmed to have been sex trafficked. The cases demonstrated a tremendous diversity of demographic and psychiatric identifying factors. These cases indicate the importance of routinely screening for trafficking victims in inpatient psychiatry settings. Identification of cases is a requisite step in providing informed and evidence-based treatments and enabling the secondary prevention of re-exploitation. Additional research is warranted given the limited current empirical research on this topic area.

  13. Does correlated color temperature affect the ability of humans to identify veins?

    DEFF Research Database (Denmark)

    Argyraki, Aikaterini; Clemmensen, Line Katrine Harder; Petersen, Paul Michael

    2016-01-01

    In the present study we provide empirical evidence and demonstrate statistically that white illumination settings can affect the human ability to identify veins in the inner hand vasculature. A special light-emitting diode lamp with high color rendering index (CRI 84–95) was developed and the eff......In the present study we provide empirical evidence and demonstrate statistically that white illumination settings can affect the human ability to identify veins in the inner hand vasculature. A special light-emitting diode lamp with high color rendering index (CRI 84–95) was developed...... and the effect of correlated color temperature was evaluated, in the range between 2600 and 5700 K at an illuminance of 40 9 lx on the ability of adult humans to identify veins. It is shown that the ability to identify veins can, on average, be increased up to 24% when white illumination settings that do...... not resemble incandescent light are applied. The illuminance reported together with the effect of white illumination settings on direct visual perception of biosamples are relevant for clinical investigations during the night. © 2015 Optical Society of America...

  14. Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

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    Neil Arvin Bretaña

    Full Text Available Viruses infect humans and progress inside the body leading to various diseases and complications. The phosphorylation of viral proteins catalyzed by host kinases plays crucial regulatory roles in enhancing replication and inhibition of normal host-cell functions. Due to its biological importance, there is a desire to identify the protein phosphorylation sites on human viruses. However, the use of mass spectrometry-based experiments is proven to be expensive and labor-intensive. Furthermore, previous studies which have identified phosphorylation sites in human viruses do not include the investigation of the responsible kinases. Thus, we are motivated to propose a new method to identify protein phosphorylation sites with its kinase substrate specificity on human viruses. The experimentally verified phosphorylation data were extracted from virPTM--a database containing 301 experimentally verified phosphorylation data on 104 human kinase-phosphorylated virus proteins. In an attempt to investigate kinase substrate specificities in viral protein phosphorylation sites, maximal dependence decomposition (MDD is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. The experimental human phosphorylation sites are collected from Phospho.ELM, grouped according to its kinase annotation, and compared with the virus MDD clusters. This investigation identifies human kinases such as CK2, PKB, CDK, and MAPK as potential kinases for catalyzing virus protein substrates as confirmed by published literature. Profile hidden Markov model is then applied to learn a predictive model for each subgroup. A five-fold cross validation evaluation on the MDD-clustered HMMs yields an average accuracy of 84.93% for Serine, and 78.05% for Threonine. Furthermore, an independent testing data collected from UniProtKB and Phospho.ELM is used to make a comparison of predictive performance on three popular kinase

  15. Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

    Science.gov (United States)

    Bretaña, Neil Arvin; Lu, Cheng-Tsung; Chiang, Chiu-Yun; Su, Min-Gang; Huang, Kai-Yao; Lee, Tzong-Yi; Weng, Shun-Long

    2012-01-01

    Viruses infect humans and progress inside the body leading to various diseases and complications. The phosphorylation of viral proteins catalyzed by host kinases plays crucial regulatory roles in enhancing replication and inhibition of normal host-cell functions. Due to its biological importance, there is a desire to identify the protein phosphorylation sites on human viruses. However, the use of mass spectrometry-based experiments is proven to be expensive and labor-intensive. Furthermore, previous studies which have identified phosphorylation sites in human viruses do not include the investigation of the responsible kinases. Thus, we are motivated to propose a new method to identify protein phosphorylation sites with its kinase substrate specificity on human viruses. The experimentally verified phosphorylation data were extracted from virPTM--a database containing 301 experimentally verified phosphorylation data on 104 human kinase-phosphorylated virus proteins. In an attempt to investigate kinase substrate specificities in viral protein phosphorylation sites, maximal dependence decomposition (MDD) is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. The experimental human phosphorylation sites are collected from Phospho.ELM, grouped according to its kinase annotation, and compared with the virus MDD clusters. This investigation identifies human kinases such as CK2, PKB, CDK, and MAPK as potential kinases for catalyzing virus protein substrates as confirmed by published literature. Profile hidden Markov model is then applied to learn a predictive model for each subgroup. A five-fold cross validation evaluation on the MDD-clustered HMMs yields an average accuracy of 84.93% for Serine, and 78.05% for Threonine. Furthermore, an independent testing data collected from UniProtKB and Phospho.ELM is used to make a comparison of predictive performance on three popular kinase-specific phosphorylation site

  16. One Health approach to identify research needs in bovine and human babesioses: workshop report

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    McElwain Terry F

    2010-04-01

    Full Text Available Abstract Background Babesia are emerging health threats to humans and animals in the United States. A collaborative effort of multiple disciplines to attain optimal health for people, animals and our environment, otherwise known as the One Health concept, was taken during a research workshop held in April 2009 to identify gaps in scientific knowledge regarding babesioses. The impetus for this analysis was the increased risk for outbreaks of bovine babesiosis, also known as Texas cattle fever, associated with the re-infestation of the U.S. by cattle fever ticks. Results The involvement of wildlife in the ecology of cattle fever ticks jeopardizes the ability of state and federal agencies to keep the national herd free of Texas cattle fever. Similarly, there has been a progressive increase in the number of cases of human babesiosis over the past 25 years due to an increase in the white-tailed deer population. Human babesiosis due to cattle-associated Babesia divergens and Babesia divergens-like organisms have begun to appear in residents of the United States. Research needs for human and bovine babesioses were identified and are presented herein. Conclusions The translation of this research is expected to provide veterinary and public health systems with the tools to mitigate the impact of bovine and human babesioses. However, economic, political, and social commitments are urgently required, including increased national funding for animal and human Babesia research, to prevent the re-establishment of cattle fever ticks and the increasing problem of human babesiosis in the United States.

  17. Data sharing platforms for de-identified data from human clinical trials.

    Science.gov (United States)

    Huser, Vojtech; Shmueli-Blumberg, Dikla

    2018-04-01

    Data sharing of de-identified individual participant data is being adopted by an increasing number of sponsors of human clinical trials. In addition to standardizing data syntax for shared trial data, semantic integration of various data elements is the focus of several initiatives that define research common data elements. This perspective article, in the first part, compares several data sharing platforms for de-identified clinical research data in terms of their size, policies and supported features. In the second part, we use a case study approach to describe in greater detail one data sharing platform (Data Share from National Institute of Drug Abuse). We present data on the past use of the platform, data formats offered, data de-identification approaches and its use of research common data elements. We conclude with a summary of current and expected future trends that facilitate secondary research use of data from completed human clinical trials.

  18. Human body as a set of biometric features identified by means of optoelectronics

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    Podbielska, Halina; Bauer, Joanna

    2005-09-01

    Human body posses many unique, singular features that are impossible to copy or forge. Nowadays, to establish and to ensure the public security requires specially designed devices and systems. Biometrics is a field of science and technology, exploiting human body characteristics for people recognition. It identifies the most characteristic and unique ones in order to design and construct systems capable to recognize people. In this paper some overview is given, presenting the achievements in biometrics. The verification and identification process is explained, along with the way of evaluation of biometric recognition systems. The most frequently human biometrics used in practice are shortly presented, including fingerprints, facial imaging (including thermal characteristic), hand geometry and iris patterns.

  19. HindIII identifies a two allele DNA polymorphism of the human cannabinoid receptor gene (CNR)

    Energy Technology Data Exchange (ETDEWEB)

    Caenazzo, L.; Hoehe, M.R.; Hsieh, W.T.; Berrettini, W.H.; Bonner, T.I.; Gershon, E.S. (National Inst. of Health, Bethesda, MD (United States))

    1991-09-11

    HCNR p5, a 0.9 kb BamHI/EcoRI fragment from the human cannabinoid receptor gene inserted into pUC19, was used as probe. The fragment is located in an intron approximately 14 kb 5{prime} of the initiation codon. This fragment is a clean single copy sequence by genomic blotting. Hybridization of human genomic DNA digested with HindIII identified a two allele RFLP with bands at 5.5 (A1) and 3.3 kb (A2). The human cannabinoid receptor gene has been genetically mapped in CEPH reference pedigrees to the centromeric/q region of chromosome 6. In situ hybridization localizes it to 6q14-q15. Codominant segregation has been observed in 26 informative two- and three-generation CEPH pedigrees and in 14 medium-sized disease families.

  20. Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.

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    Sun Hee Ahn

    Full Text Available Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host's inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection and was validated in outbred mice (AUC>0.97. A S. aureus classifier derived from a cohort of 94 human subjects distinguished S. aureus blood stream infection (BSI from healthy subjects (AUC 0.99 and E. coli BSI (AUC 0.84. Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84. Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.92, respectively. The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.

  1. SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development

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    Rhys J.P. Skelton

    2014-07-01

    Full Text Available The study of human cardiogenesis would benefit from a detailed cell lineage fate map akin to that established for the haematopoietic lineages. Here we sought to define cell lineage relationships based on the expression of NKX2-5 and the cell surface markers VCAM1, SIRPA and CD34 during human cardiovascular development. Expression of NKX2-5GFP was used to identify cardiac progenitors and cardiomyocytes generated during the differentiation of NKX2-5GFP/w human embryonic stem cells (hESCs. Cardiovascular cell lineages sub-fractionated on the basis of SIRPA, VCAM1 and CD34 expression were assayed for differentiation potential and gene expression. The NKX2-5posCD34pos population gave rise to endothelial cells that rapidly lost NKX2-5 expression in culture. Conversely, NKX2-5 expression was maintained in myocardial committed cells, which progressed from being NKX2-5posSIRPApos to NKX2-5posSIRPAposVCAM1pos. Up-regulation of VCAM1 was accompanied by the expression of myofilament markers and reduced clonal capacity, implying a restriction of cell fate potential. Combinatorial expression of NKX2-5, SIRPA, VCAM1 and CD34 can be used to define discrete stages of cardiovascular cell lineage differentiation. These markers identify specific stages of cardiomyocyte and endothelial lineage commitment and, thus provide a scaffold for establishing a fate map of early human cardiogenesis.

  2. Identifying Human Phenotype Terms by Combining Machine Learning and Validation Rules

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    Manuel Lobo

    2017-01-01

    Full Text Available Named-Entity Recognition is commonly used to identify biological entities such as proteins, genes, and chemical compounds found in scientific articles. The Human Phenotype Ontology (HPO is an ontology that provides a standardized vocabulary for phenotypic abnormalities found in human diseases. This article presents the Identifying Human Phenotypes (IHP system, tuned to recognize HPO entities in unstructured text. IHP uses Stanford CoreNLP for text processing and applies Conditional Random Fields trained with a rich feature set, which includes linguistic, orthographic, morphologic, lexical, and context features created for the machine learning-based classifier. However, the main novelty of IHP is its validation step based on a set of carefully crafted manual rules, such as the negative connotation analysis, that combined with a dictionary can filter incorrectly identified entities, find missed entities, and combine adjacent entities. The performance of IHP was evaluated using the recently published HPO Gold Standardized Corpora (GSC, where the system Bio-LarK CR obtained the best F-measure of 0.56. IHP achieved an F-measure of 0.65 on the GSC. Due to inconsistencies found in the GSC, an extended version of the GSC was created, adding 881 entities and modifying 4 entities. IHP achieved an F-measure of 0.863 on the new GSC.

  3. Identifying blood biomarkers and physiological processes that distinguish humans with superior performance under psychological stress.

    Directory of Open Access Journals (Sweden)

    Amanda M Cooksey

    2009-12-01

    Full Text Available Attrition of students from aviation training is a serious financial and operational concern for the U.S. Navy. Each late stage navy aviator training failure costs the taxpayer over $1,000,000 and ultimately results in decreased operational readiness of the fleet. Currently, potential aviators are selected based on the Aviation Selection Test Battery (ASTB, which is a series of multiple-choice tests that evaluate basic and aviation-related knowledge and ability. However, the ASTB does not evaluate a person's response to stress. This is important because operating sophisticated aircraft demands exceptional performance and causes high psychological stress. Some people are more resistant to this type of stress, and consequently better able to cope with the demands of naval aviation, than others.Although many psychological studies have examined psychological stress resistance none have taken advantage of the human genome sequence. Here we use high-throughput -omic biology methods and a novel statistical data normalization method to identify plasma proteins associated with human performance under psychological stress. We identified proteins involved in four basic physiological processes: innate immunity, cardiac function, coagulation and plasma lipid physiology.The proteins identified here further elucidate the physiological response to psychological stress and suggest a hypothesis that stress-susceptible pilots may be more prone to shock. This work also provides potential biomarkers for screening humans for capability of superior performance under stress.

  4. Human Trafficking in Ethiopia: A Scoping Review to Identify Gaps in Service Delivery, Research, and Policy.

    Science.gov (United States)

    Beck, Dana C; Choi, Kristen R; Munro-Kramer, Michelle L; Lori, Jody R

    2017-12-01

    The purpose of this review is to integrate evidence on human trafficking in Ethiopia and identify gaps and recommendations for service delivery, research and training, and policy. A scoping literature review approach was used to systematically search nursing, medical, psychological, law, and international databases and synthesize information on a complex, understudied topic. The search yielded 826 articles, and 39 met the predetermined criteria for inclusion in the review. Trafficking in Ethiopia has occurred internally and externally in the form of adult and child labor and sex trafficking. There were also some reports of organ trafficking and other closely related human rights violations, such as child marriage, child soldiering, and exploitative intercountry adoption. Risk factors for trafficking included push factors (poverty, political instability, economic problems, and gender discrimination) and pull factors (demand for cheap labor). Trafficking was associated with poor health and economic outcomes for victims. Key recommendations for service delivery, research and training, and policy are identified, including establishing comprehensive services for survivor rehabilitation and reintegration, conducting quantitative health outcomes research, and reforming policy around migration and trafficking. Implementing the recommendations identified by this review will allow policy makers, researchers, and practitioners to take meaningful steps toward confronting human trafficking in Ethiopia.

  5. Identifying domestic and international sex-trafficking victims during human service provision.

    Science.gov (United States)

    Macy, Rebecca J; Graham, Laurie M

    2012-04-01

    Children, youth, and adults of both genders are sex trafficked into and throughout the United States every day. Regrettably, little attention has been given to how human service providers might identify the sex-trafficking victims they are likely to encounter. To address this knowledge gap, the authors review 20 documents with the aim of detecting and synthesizing service identification recommendations in the scientific literature, government reports, and documents produced by organizations working with sex-trafficking victims. The review shows consensus regarding identification recommendations, including (a) trafficking indicators, (b) victim interaction strategies, (c) immediate response strategies, and (d) child-specific information. The review also shows consensus regarding screening questions that are important for service providers to use in identifying sex-trafficking victims. These questions relate to the victims' safety, employment, living environment, and travel and immigration status in addition to specific questions used with children and youth. The review results offer human service providers a preliminary set of screening strategies and questions that can be used to identify sex-trafficking victims in the context of human services. Building on the review findings, the authors offer policy and research recommendations.

  6. Nodule worm infection in humans and wild primates in Uganda: cryptic species in a newly identified region of human transmission.

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    Ria R Ghai

    Full Text Available Soil-transmitted helminths (STHs are a major health concern in tropical and sub-tropical countries. Oesophagostomum infection is considered endemic to West Africa but has also been identified in Uganda, East Africa, among primates (including humans. However, the taxonomy and ecology of Oesophagostomum in Uganda have not been studied, except for in chimpanzees (Pan troglodytes, which are infected by both O. bifurcum and O. stephanostomum.We studied Oesophagostomum in Uganda in a community of non-human primates that live in close proximity to humans. Prevalence estimates based on microscopy were lower than those based on polymerase chain reaction (PCR, indicating greater sensitivity of PCR. Prevalence varied among host species, with humans and red colobus (Procolobus rufomitratus infected at lowest prevalence (25% and 41% by PCR, respectively, and chimpanzees, olive baboons (Papio anubis, and l'hoest monkeys (Cercopithecus lhoesti infected at highest prevalence (100% by PCR in all three species. Phylogenetic regression showed that primates travelling further and in smaller groups are at greatest risk of infection. Molecular phylogenetic analyses revealed three cryptic clades of Oesophagostomum that were not distinguishable based on morphological characteristics of their eggs. Of these, the clade with the greatest host range had not previously been described genetically. This novel clade infects humans, as well as five other species of primates.Multiple cryptic forms of Oesophagostomum circulate in the people and primates of western Uganda, and parasite clades differ in host range and cross-species transmission potential. Our results expand knowledge about human Oesophagostomum infection beyond the West African countries of Togo and Ghana, where the parasite is a known public health concern. Oesophagostomum infection in humans may be common throughout Sub-Saharan Africa, and the transmission of this neglected STH among primates, including zoonotic

  7. A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs.

    Science.gov (United States)

    Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F; Lecuit, Marc

    2016-05-12

    Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents.

  8. Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer

    Science.gov (United States)

    Duffy, Supipi; Fam, Hok Khim; Wang, Yi Kan; Styles, Erin B.; Kim, Jung-Hyun; Ang, J. Sidney; Singh, Tejomayee; Larionov, Vladimir; Shah, Sohrab P.; Andrews, Brenda; Boerkoel, Cornelius F.; Hieter, Philip

    2016-01-01

    Somatic copy number amplification and gene overexpression are common features of many cancers. To determine the role of gene overexpression on chromosome instability (CIN), we performed genome-wide screens in the budding yeast for yeast genes that cause CIN when overexpressed, a phenotype we refer to as dosage CIN (dCIN), and identified 245 dCIN genes. This catalog of genes reveals human orthologs known to be recurrently overexpressed and/or amplified in tumors. We show that two genes, TDP1, a tyrosyl-DNA-phosphdiesterase, and TAF12, an RNA polymerase II TATA-box binding factor, cause CIN when overexpressed in human cells. Rhabdomyosarcoma lines with elevated human Tdp1 levels also exhibit CIN that can be partially rescued by siRNA-mediated knockdown of TDP1. Overexpression of dCIN genes represents a genetic vulnerability that could be leveraged for selective killing of cancer cells through targeting of an unlinked synthetic dosage lethal (SDL) partner. Using SDL screens in yeast, we identified a set of genes that when deleted specifically kill cells with high levels of Tdp1. One gene was the histone deacetylase RPD3, for which there are known inhibitors. Both HT1080 cells overexpressing hTDP1 and rhabdomyosarcoma cells with elevated levels of hTdp1 were more sensitive to histone deacetylase inhibitors valproic acid (VPA) and trichostatin A (TSA), recapitulating the SDL interaction in human cells and suggesting VPA and TSA as potential therapeutic agents for tumors with elevated levels of hTdp1. The catalog of dCIN genes presented here provides a candidate list to identify genes that cause CIN when overexpressed in cancer, which can then be leveraged through SDL to selectively target tumors. PMID:27551064

  9. An Exploration of Human Well-Being Bundles as Identifiers of Ecosystem Service Use Patterns.

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    Maike Hamann

    Full Text Available We take a social-ecological systems perspective to investigate the linkages between ecosystem services and human well-being in South Africa. A recent paper identified different types of social-ecological systems in the country, based on distinct bundles of ecosystem service use. These system types were found to represent increasingly weak direct feedbacks between nature and people, from rural "green-loop" communities to urban "red-loop" societies. Here we construct human well-being bundles and explore whether the well-being bundles can be used to identify the same social-ecological system types that were identified using bundles of ecosystem service use. Based on national census data, we found three distinct well-being bundle types that are mainly characterized by differences in income, unemployment and property ownership. The distribution of these well-being bundles approximates the distribution of ecosystem service use bundles to a substantial degree: High levels of income and education generally coincided with areas characterised by low levels of direct ecosystem service use (or red-loop systems, while the majority of low well-being areas coincided with medium and high levels of direct ecosystem service use (or transition and green-loop systems. However, our results indicate that transformations from green-loop to red-loop systems do not always entail an immediate improvement in well-being, which we suggest may be due to a time lag between changes in the different system components. Using human well-being bundles as an indicator of social-ecological dynamics may be useful in other contexts since it is based on socio-economic data commonly collected by governments, and provides important insights into the connections between ecosystem services and human well-being at policy-relevant sub-national scales.

  10. An Exploration of Human Well-Being Bundles as Identifiers of Ecosystem Service Use Patterns.

    Science.gov (United States)

    Hamann, Maike; Biggs, Reinette; Reyers, Belinda

    2016-01-01

    We take a social-ecological systems perspective to investigate the linkages between ecosystem services and human well-being in South Africa. A recent paper identified different types of social-ecological systems in the country, based on distinct bundles of ecosystem service use. These system types were found to represent increasingly weak direct feedbacks between nature and people, from rural "green-loop" communities to urban "red-loop" societies. Here we construct human well-being bundles and explore whether the well-being bundles can be used to identify the same social-ecological system types that were identified using bundles of ecosystem service use. Based on national census data, we found three distinct well-being bundle types that are mainly characterized by differences in income, unemployment and property ownership. The distribution of these well-being bundles approximates the distribution of ecosystem service use bundles to a substantial degree: High levels of income and education generally coincided with areas characterised by low levels of direct ecosystem service use (or red-loop systems), while the majority of low well-being areas coincided with medium and high levels of direct ecosystem service use (or transition and green-loop systems). However, our results indicate that transformations from green-loop to red-loop systems do not always entail an immediate improvement in well-being, which we suggest may be due to a time lag between changes in the different system components. Using human well-being bundles as an indicator of social-ecological dynamics may be useful in other contexts since it is based on socio-economic data commonly collected by governments, and provides important insights into the connections between ecosystem services and human well-being at policy-relevant sub-national scales.

  11. Apolipoprotein A5: A newly identified gene impacting plasmatriglyceride levels in humans and mice

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Rubin, Edward M.

    2002-09-15

    Apolipoprotein A5 (APOA5) is a newly described member of theapolipoprotein gene family whose initial discovery arose from comparativesequence analysis of the mammalian APOA1/C3/A4 gene cluster. Functionalstudies in mice indicated that alteration in the level of APOA5significantly impacted plasma triglyceride concentrations. Miceover-expressing human APOA5 displayed significantly reducedtriglycerides, while mice lacking apoA5 had a large increase in thislipid parameter. Studies in humans have also suggested an important rolefor APOA5 in determining plasma triglyceride concentrations. In theseexperiments, polymorphisms in the human gene were found to define severalcommon haplotypes that were associated with significant changes intriglyceride concentrations in multiple populations. Several separateclinical studies have provided consistent and strong support for theeffect with 24 percent of Caucasians, 35 percent of African-Americans and53 percent of Hispanics carrying APOA5 haplotypes associated withincreased plasma triglyceride levels. In summary, APOA5 represents anewly discovered gene involved in triglyceride metabolism in both humansand mice whose mechanism of action remains to be deciphered.

  12. Identifying environmental risk factors and mapping the risk of human West Nile virus in South Dakota.

    Science.gov (United States)

    Hess, A.; Davis, J. K.; Wimberly, M. C.

    2017-12-01

    Human West Nile virus (WNV) first arrived in the USA in 1999 and has since then spread across the country. Today, the highest incidence rates are found in the state of South Dakota. The disease occurrence depends on the complex interaction between the mosquito vector, the bird host and the dead-end human host. Understanding the spatial domain of this interaction and being able to identify disease transmission hotspots is crucial for effective disease prevention and mosquito control. In this study we use geospatial environmental information to understand what drives the spatial distribution of cases of human West Nile virus in South Dakota and to map relative infection risk across the state. To map the risk of human West Nile virus in South Dakota, we used geocoded human case data from the years 2004-2016. Satellite data from the Landsat ETM+ and MODIS for the years 2003 to 2016 were used to characterize environmental patterns. From these datasets we calculated indices, such as the normalized differenced vegetation index (NDVI) and the normalized differenced water index (NDWI). In addition, datasets such as the National Land Data Assimilation System (NLDAS), National Land Cover Dataset (NLCD), National Wetland inventory (NWI), National Elevation Dataset (NED) and Soil Survey Geographic Database (SSURGO) were utilized. Environmental variables were summarized for a buffer zone around the case and control points. We used a boosted regression tree model to identify the most important variables describing the risk of WNV infection. We generated a risk map by applying this model across the entire state. We found that the highest relative risk is present in the James River valley in northeastern South Dakota. Factors that were identified as influencing the transmission risk include inter-annual variability of vegetation cover, water availability and temperature. Land covers such as grasslands, low developed areas and wetlands were also found to be good predictors for human

  13. Using a Delphi Method to Identify Human Factors Contributing to Nursing Errors.

    Science.gov (United States)

    Roth, Cheryl; Brewer, Melanie; Wieck, K Lynn

    2017-07-01

    The purpose of this study was to identify human factors associated with nursing errors. Using a Delphi technique, this study used feedback from a panel of nurse experts (n = 25) on an initial qualitative survey questionnaire followed by summarizing the results with feedback and confirmation. Synthesized factors regarding causes of errors were incorporated into a quantitative Likert-type scale, and the original expert panel participants were queried a second time to validate responses. The list identified 24 items as most common causes of nursing errors, including swamping and errors made by others that nurses are expected to recognize and fix. The responses provided a consensus top 10 errors list based on means with heavy workload and fatigue at the top of the list. The use of the Delphi survey established consensus and developed a platform upon which future study of nursing errors can evolve as a link to future solutions. This list of human factors in nursing errors should serve to stimulate dialogue among nurses about how to prevent errors and improve outcomes. Human and system failures have been the subject of an abundance of research, yet nursing errors continue to occur. © 2016 Wiley Periodicals, Inc.

  14. Pilot Critical Incident Reports as a Means to Identify Human Factors of Remotely Piloted Aircraft

    Science.gov (United States)

    Hobbs, Alan; Cardoza, Colleen; Null, Cynthia

    2016-01-01

    It has been estimated that aviation accidents are typically preceded by numerous minor incidents arising from the same causal factors that ultimately produced the accident. Accident databases provide in-depth information on a relatively small number of occurrences, however incident databases have the potential to provide insights into the human factors of Remotely Piloted Aircraft System (RPAS) operations based on a larger volume of less-detailed reports. Currently, there is a lack of incident data dealing with the human factors of unmanned aircraft systems. An exploratory study is being conducted to examine the feasibility of collecting voluntary critical incident reports from RPAS pilots. Twenty-three experienced RPAS pilots volunteered to participate in focus groups in which they described critical incidents from their own experience. Participants were asked to recall (1) incidents that revealed a system flaw, or (2) highlighted a case where the human operator contributed to system resilience or mission success. Participants were asked to only report incidents that could be included in a public document. During each focus group session, a note taker produced a de-identified written record of the incident narratives. At the end of the session, participants reviewed each written incident report, and made edits and corrections as necessary. The incidents were later analyzed to identify contributing factors, with a focus on design issues that either hindered or assisted the pilot during the events. A total of 90 incidents were reported. Human factor issues included the impact of reduced sensory cues, traffic separation in the absence of an out-the-window view, control latencies, vigilance during monotonous and ultra-long endurance flights, control station design considerations, transfer of control between control stations, the management of lost link procedures, and decision-making during emergencies. Pilots participated willingly and enthusiastically in the study

  15. New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes.

    Science.gov (United States)

    Parker, Brian J; Moltke, Ida; Roth, Adam; Washietl, Stefan; Wen, Jiayu; Kellis, Manolis; Breaker, Ronald; Pedersen, Jakob Skou

    2011-11-01

    Regulatory RNA structures are often members of families with multiple paralogous instances across the genome. Family members share functional and structural properties, which allow them to be studied as a whole, facilitating both bioinformatic and experimental characterization. We have developed a comparative method, EvoFam, for genome-wide identification of families of regulatory RNA structures, based on primary sequence and secondary structure similarity. We apply EvoFam to a 41-way genomic vertebrate alignment. Genome-wide, we identify 220 human, high-confidence families outside protein-coding regions comprising 725 individual structures, including 48 families with known structural RNA elements. Known families identified include both noncoding RNAs, e.g., miRNAs and the recently identified MALAT1/MEN β lincRNA family; and cis-regulatory structures, e.g., iron-responsive elements. We also identify tens of new families supported by strong evolutionary evidence and other statistical evidence, such as GO term enrichments. For some of these, detailed analysis has led to the formulation of specific functional hypotheses. Examples include two hypothesized auto-regulatory feedback mechanisms: one involving six long hairpins in the 3'-UTR of MAT2A, a key metabolic gene that produces the primary human methyl donor S-adenosylmethionine; the other involving a tRNA-like structure in the intron of the tRNA maturation gene POP1. We experimentally validate the predicted MAT2A structures. Finally, we identify potential new regulatory networks, including large families of short hairpins enriched in immunity-related genes, e.g., TNF, FOS, and CTLA4, which include known transcript destabilizing elements. Our findings exemplify the diversity of post-transcriptional regulation and provide a resource for further characterization of new regulatory mechanisms and families of noncoding RNAs.

  16. High-Dimensional Phenotyping Identifies Age-Emergent Cells in Human Mammary Epithelia

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    Fanny A. Pelissier Vatter

    2018-04-01

    Full Text Available Summary: Aging is associated with tissue-level changes in cellular composition that are correlated with increased susceptibility to disease. Aging human mammary tissue shows skewed progenitor cell potency, resulting in diminished tumor-suppressive cell types and the accumulation of defective epithelial progenitors. Quantitative characterization of these age-emergent human cell subpopulations is lacking, impeding our understanding of the relationship between age and cancer susceptibility. We conducted single-cell resolution proteomic phenotyping of healthy breast epithelia from 57 women, aged 16–91 years, using mass cytometry. Remarkable heterogeneity was quantified within the two mammary epithelial lineages. Population partitioning identified a subset of aberrant basal-like luminal cells that accumulate with age and originate from age-altered progenitors. Quantification of age-emergent phenotypes enabled robust classification of breast tissues by age in healthy women. This high-resolution mapping highlighted specific epithelial subpopulations that change with age in a manner consistent with increased susceptibility to breast cancer. : Vatter et al. find that single-cell mass cytometry of human mammary epithelial cells from 57 women, from 16 to 91 years old, depicts an in-depth phenotyping of aging mammary epithelia. Subpopulations of altered luminal and progenitor cells that accumulate with age may be at increased risk for oncogenic transformation. Keywords: human mammary epithelia, aging, mass cytometry, single-cell analysis, heterogeneity, breast cancer

  17. The use of human factors methods to identify and mitigate safety issues in radiation therapy

    International Nuclear Information System (INIS)

    Chan, Alvita J.; Islam, Mohammad K.; Rosewall, Tara; Jaffray, David A.; Easty, Anthony C.; Cafazzo, Joseph A.

    2010-01-01

    Background and purpose: New radiation therapy technologies can enhance the quality of treatment and reduce error. However, the treatment process has become more complex, and radiation dose is not always delivered as intended. Using human factors methods, a radiotherapy treatment delivery process was evaluated, and a redesign was undertaken to determine the effect on system safety. Material and methods: An ethnographic field study and workflow analysis was conducted to identify human factors issues of the treatment delivery process. To address specific issues, components of the user interface were redesigned through a user-centered approach. Sixteen radiation therapy students were then used to experimentally evaluate the redesigned system through a usability test to determine the effectiveness in mitigating use errors. Results: According to findings from the usability test, the redesigned system successfully reduced the error rates of two common errors (p < .04 and p < .01). It also improved the mean task completion time by 5.5% (p < .02) and achieved a higher level of user satisfaction. Conclusions: These findings demonstrated the importance and benefits of applying human factors methods in the design of radiation therapy systems. Many other opportunities still exist to improve patient safety in this area using human factors methods.

  18. Using molecular tools to identify the geographical origin of a case of human brucellosis.

    Science.gov (United States)

    Muchowski, J K; Koylass, M S; Dainty, A C; Stack, J A; Perrett, L; Whatmore, A M; Perrier, C; Chircop, S; Demicoli, N; Gatt, A B; Caruana, P A; Gopaul, K K

    2015-10-01

    Although Malta is historically linked with the zoonosis brucellosis, there had not been a case of the disease in either the human or livestock population for several years. However, in July 2013 a case of human brucellosis was identified on the island. To determine whether this recent case originated in Malta, four isolates from this case were subjected to molecular analysis. Molecular profiles generated using multilocus sequence analysis and multilocus variable number tandem repeat for the recent human case isolates and 11 Brucella melitensis strains of known Maltese origin were compared with others held on in-house and global databases. While the 11 isolates of Maltese origin formed a distinct cluster, the recent human isolation was not associated with these strains but instead clustered with isolates originating from the Horn of Africa. These data was congruent with epidemiological trace-back showed that the individual had travelled to Malta from Eritrea. This work highlights the potential of using molecular typing data to aid in epidemiological trace-back of Brucella isolations and assist in monitoring of the effectiveness of brucellosis control schemes.

  19. What's the risk? Identifying potential human pathogens within grey-headed flying foxes faeces.

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    Rebekah Henry

    Full Text Available Pteropus poliocephalus (grey-headed flying foxes are recognised vectors for a range of potentially fatal human pathogens. However, to date research has primarily focused on viral disease carriage, overlooking bacterial pathogens, which also represent a significant human disease risk. The current study applied 16S rRNA amplicon sequencing, community analysis and a multi-tiered database OTU picking approach to identify faecal-derived zoonotic bacteria within two colonies of P. poliocephalus from Victoria, Australia. Our data show that sequences associated with Enterobacteriaceae (62.8% ± 24.7%, Pasteurellaceae (19.9% ± 25.7% and Moraxellaceae (9.4% ± 11.8% dominate flying fox faeces. Further colony specific differences in bacterial faecal colonisation patterns were also identified. In total, 34 potential pathogens, representing 15 genera, were identified. However, species level definition was only possible for Clostridium perfringens, which likely represents a low infectious risk due to the low proportion observed within the faeces and high infectious dose required for transmission. In contrast, sequences associated with other pathogenic species clusters such as Haemophilus haemolyticus-H. influenzae and Salmonella bongori-S. enterica, were present at high proportions in the faeces, and due to their relatively low infectious doses and modes of transmissions, represent a greater potential human disease risk. These analyses of the microbial community composition of Pteropus poliocephalus have significantly advanced our understanding of the potential bacterial disease risk associated with flying foxes and should direct future epidemiological and quantitative microbial risk assessments to further define the health risks presented by these animals.

  20. On the Use of Biomineral Oxygen Isotope Data to Identify Human Migrants in the Archaeological Record: Intra-Sample Variation, Statistical Methods and Geographical Considerations.

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    Emma Lightfoot

    Full Text Available Oxygen isotope analysis of archaeological skeletal remains is an increasingly popular tool to study past human migrations. It is based on the assumption that human body chemistry preserves the δ18O of precipitation in such a way as to be a useful technique for identifying migrants and, potentially, their homelands. In this study, the first such global survey, we draw on published human tooth enamel and bone bioapatite data to explore the validity of using oxygen isotope analyses to identify migrants in the archaeological record. We use human δ18O results to show that there are large variations in human oxygen isotope values within a population sample. This may relate to physiological factors influencing the preservation of the primary isotope signal, or due to human activities (such as brewing, boiling, stewing, differential access to water sources and so on causing variation in ingested water and food isotope values. We compare the number of outliers identified using various statistical methods. We determine that the most appropriate method for identifying migrants is dependent on the data but is likely to be the IQR or median absolute deviation from the median under most archaeological circumstances. Finally, through a spatial assessment of the dataset, we show that the degree of overlap in human isotope values from different locations across Europe is such that identifying individuals' homelands on the basis of oxygen isotope analysis alone is not possible for the regions analysed to date. Oxygen isotope analysis is a valid method for identifying first-generation migrants from an archaeological site when used appropriately, however it is difficult to identify migrants using statistical methods for a sample size of less than c. 25 individuals. In the absence of local previous analyses, each sample should be treated as an individual dataset and statistical techniques can be used to identify migrants, but in most cases pinpointing a specific

  1. Strong memory in time series of human magnetoencephalograms can identify photosensitive epilepsy

    International Nuclear Information System (INIS)

    Yulmetyev, R. M.; Yulmetyeva, D. G.; Haenggi, P.; Shimojo, S.; Bhattacharya, J.

    2007-01-01

    To discuss the salient role of statistical memory effects in human brain functioning, we have analyzed a set of stochastic memory quantifiers that reflects the dynamical characteristics of neuromagnetic responses of magnetoencephalographic signals to a flickering stimulus of different color combinations from a group of control subjects, and compared them with those for a patient with photosensitive epilepsy. We have discovered that the emergence of strong memory and the accompanying transition to a regular and robust regime of chaotic behavior of signals in separate areas for a patient most likely identifies the regions where the protective mechanism against the occurrence of photosensitive epilepsy is located

  2. Comprehensive metabolomics identified lipid peroxidation as a prominent feature in human plasma of patients with coronary heart diseases

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    Jianhong Lu

    2017-08-01

    Full Text Available Coronary heart disease (CHD is a complex human disease associated with inflammation and oxidative stress. The underlying mechanisms and diagnostic biomarkers for the different types of CHD remain poorly defined. Metabolomics has been increasingly recognized as an enabling technique with the potential to identify key metabolomic features in an attempt to understand the pathophysiology and differentiate different stages of CHD. We performed comprehensive metabolomic analysis in human plasma from 28 human subjects with stable angina (SA, myocardial infarction (MI, and healthy control (HC. Subsequent analysis demonstrated a uniquely altered metabolic profile in these CHD: a total of 18, 37 and 36 differential metabolites were identified to distinguish SA from HC, MI from SA, and MI from HC groups respectively. Among these metabolites, glycerophospholipid (GPL metabolism emerged as the most significantly disturbed pathway. Next, we used a targeted metabolomic approach to systematically analyze GPL, oxidized phospholipid (oxPL, and downstream metabolites derived from polyunsaturated fatty acids (PUFAs, such as arachidonic acid and linoleic acid. Surprisingly, lipids associated with lipid peroxidation (LPO pathways including oxidized PL and isoprostanes, isomers of prostaglandins, were significantly elevated in plasma of MI patients comparing to HC and SA, consistent with the notion that oxidative stress-induced LPO is a prominent feature in CHD. Our studies using the state-of-the-art metabolomics help to understand the underlying biological mechanisms involved in the pathogenesis of CHD; LPO metabolites may serve as potential biomarkers to differentiation MI from SA and HC. Keywords: Metabolomics, Lipid peroxidation, Lipidomics, Myocardial infarction, Isoprostanes, Coronary heart disease (CHD

  3. Phosphoproteomic Analysis Identifies Signaling Pathways Regulated by Curcumin in Human Colon Cancer Cells.

    Science.gov (United States)

    Sato, Tatsuhiro; Higuchi, Yutaka; Shibagaki, Yoshio; Hattori, Seisuke

    2017-09-01

    Curcumin, a major polyphenol of the spice turmeric, acts as a potent chemopreventive and chemotherapeutic agent in several cancer types, including colon cancer. Although various proteins have been shown to be affected by curcumin, how curcumin exerts its anticancer activity is not fully understood. Phosphoproteomic analyses were performed using SW480 and SW620 human colon cancer cells to identify curcumin-affected signaling pathways. Curcumin inhibited the growth of the two cell lines in a dose-dependent manner. Thirty-nine curcumin-regulated phosphoproteins were identified, five of which are involved in cancer signaling pathways. Detailed analyses revealed that the mTORC1 and p53 signaling pathways are main targets of curcumin. Our results provide insight into the molecular mechanisms of the anticancer activities of curcumin and future molecular targets for its clinical application. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Individually identifiable body odors are produced by the gorilla and discriminated by humans.

    Science.gov (United States)

    Hepper, Peter G; Wells, Deborah L

    2010-05-01

    Many species produce odor cues that enable them to be identified individually, as well as providing other socially relevant information. Study of the role of odor cues in the social behavior of great apes is noticeable by its absence. Olfaction has been viewed as having little role in guiding behavior in these species. This study examined whether Western lowland gorillas produce an individually identifiable odor. Odor samples were obtained by placing cloths in the gorilla's den. A delayed matching to sample task was used with human participants (n = 100) to see if they were able to correctly match a target odor sample to a choice of either: 2 odors (the target sample and another, Experiment 1) and 6 odors (the target sample and 5 others, Experiment 2). Participants were correctly able to identify the target odor when given either 2 or 6 matches. Subjects made fewest errors when matching the odor of the silverback, whereas matching the odors of the young gorillas produced most errors. The results indicate that gorillas do produce individually identifiable body odors and introduce the possibility that odor cues may play a role in gorilla social behavior.

  5. Identifying the gaps: Armenian health care legislation and human rights in patient care protections.

    Science.gov (United States)

    Zopunyan, Violeta; Krmoyan, Suren; Quinn, Ryan

    2013-12-12

    Since the collapse of the Soviet Union, the Republic of Armenia has undergone an extensive legislative overhaul. Although a number of developments have aimed to improve the quality and accessibility of Armenia's health care system, a host of factors has prevented the country from fully introducing measures to ensure respect for human rights in patient care. In particular, inadequate health care financing continues to oblige patients to make both formal and informal payments to obtain basic medical care and services. More generally, a lack of oversight and monitoring mechanisms has obstructed the implementation of Armenia's commitments to human rights in several international agreements. Within the framework of a broader project on promoting human rights in patient care, research was carried out to examine Armenia’s health care legislation with the aim of identifying gaps in comparison with international and regional standards. This research was designed using the 14 rights enshrined in the European Charter on Patient Rights as guiding principles, along with domestic legal acts relevant to the rights of health care providers. The gaps analysis revealed numerous problems with Armenian legislation governing the relationships between stakeholders in health care service delivery. It also identified several practical inconsistencies with the international legal instruments ratified by the Armenian government. These legislative shortcomings are illustrated by highlighting key health-related rights violations experienced by patients and their health care providers, and by indicating opportunities for improved rights protections. A full list of human rights relevant to patient care and recommendations for promoting them in the Armenian context is provided in Tables 1 and 2. A number of initiatives must be undertaken in order to promote the full spectrum of human rights in patient care in Armenia. This section highlights certain recommendations flowing from the findings of

  6. Identifying recombinants in human and primate immunodeficiency virus sequence alignments using quartet scanning

    Directory of Open Access Journals (Sweden)

    Martin Darren P

    2009-04-01

    Full Text Available Abstract Background Recombination has a profound impact on the evolution of viruses, but characterizing recombination patterns in molecular sequences remains a challenging endeavor. Despite its importance in molecular evolutionary studies, identifying the sequences that exhibit such patterns has received comparatively less attention in the recombination detection framework. Here, we extend a quartet-mapping based recombination detection method to enable identification of recombinant sequences without prior specifications of either query and reference sequences. Through simulations we evaluate different recombinant identification statistics and significance tests. We compare the quartet approach with triplet-based methods that employ additional heuristic tests to identify parental and recombinant sequences. Results Analysis of phylogenetic simulations reveal that identifying the descendents of relatively old recombination events is a challenging task for all methods available, and that quartet scanning performs relatively well compared to the triplet based methods. The use of quartet scanning is further demonstrated by analyzing both well-established and putative HIV-1 recombinant strains. In agreement with recent findings, we provide evidence that the presumed circulating recombinant CRF02_AG is a 'pure' lineage, whereas the presumed parental lineage subtype G has a recombinant origin. We also demonstrate HIV-1 intrasubtype recombination, confirm the hybrid origin of SIV in chimpanzees and further disentangle the recombinant history of SIV lineages in a primate immunodeficiency virus data set. Conclusion Quartet scanning makes a valuable addition to triplet-based methods for identifying recombinant sequences without prior specifications of either query and reference sequences. The new method is available in the VisRD v.3.0 package http://www.cmp.uea.ac.uk/~vlm/visrd.

  7. Novel mitochondria-targeted heat-soluble proteins identified in the anhydrobiotic Tardigrade improve osmotic tolerance of human cells.

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    Sae Tanaka

    Full Text Available Tardigrades are able to tolerate almost complete dehydration through transition to a metabolically inactive state, called "anhydrobiosis". Late Embryogenesis Abundant (LEA proteins are heat-soluble proteins involved in the desiccation tolerance of many anhydrobiotic organisms. Tardigrades, Ramazzottius varieornatus, however, express predominantly tardigrade-unique heat-soluble proteins: CAHS (Cytoplasmic Abundant Heat Soluble and SAHS (Secretory Abundant Heat Soluble proteins, which are secreted or localized in most intracellular compartments, except the mitochondria. Although mitochondrial integrity is crucial to ensure cellular survival, protective molecules for mitochondria have remained elusive. Here, we identified two novel mitochondrial heat-soluble proteins, RvLEAM and MAHS (Mitochondrial Abundant Heat Soluble, as potent mitochondrial protectants from Ramazzottius varieornatus. RvLEAM is a group3 LEA protein and immunohistochemistry confirmed its mitochondrial localization in tardigrade cells. MAHS-green fluorescent protein fusion protein localized in human mitochondria and was heat-soluble in vitro, though no sequence similarity with other known proteins was found, and one region was conserved among tardigrades. Furthermore, we demonstrated that RvLEAM protein as well as MAHS protein improved the hyperosmotic tolerance of human cells. The findings of the present study revealed that tardigrade mitochondria contain at least two types of heat-soluble proteins that might have protective roles in water-deficient environments.

  8. Investigating Salmonella Eko from Various Sources in Nigeria by Whole Genome Sequencing to Identify the Source of Human Infections.

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    Pimlapas Leekitcharoenphon

    Full Text Available Twenty-six Salmonella enterica serovar Eko isolated from various sources in Nigeria were investigated by whole genome sequencing to identify the source of human infections. Diversity among the isolates was observed and camel and cattle were identified as the primary reservoirs and the most likely source of the human infections.

  9. Alternative splicing events identified in human embryonic stem cells and neural progenitors.

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    Gene W Yeo

    2007-10-01

    Full Text Available Human embryonic stem cells (hESCs and neural progenitor (NP cells are excellent models for recapitulating early neuronal development in vitro, and are key to establishing strategies for the treatment of degenerative disorders. While much effort had been undertaken to analyze transcriptional and epigenetic differences during the transition of hESC to NP, very little work has been performed to understand post-transcriptional changes during neuronal differentiation. Alternative RNA splicing (AS, a major form of post-transcriptional gene regulation, is important in mammalian development and neuronal function. Human ESC, hESC-derived NP, and human central nervous system stem cells were compared using Affymetrix exon arrays. We introduced an outlier detection approach, REAP (Regression-based Exon Array Protocol, to identify 1,737 internal exons that are predicted to undergo AS in NP compared to hESC. Experimental validation of REAP-predicted AS events indicated a threshold-dependent sensitivity ranging from 56% to 69%, at a specificity of 77% to 96%. REAP predictions significantly overlapped sets of alternative events identified using expressed sequence tags and evolutionarily conserved AS events. Our results also reveal that focusing on differentially expressed genes between hESC and NP will overlook 14% of potential AS genes. In addition, we found that REAP predictions are enriched in genes encoding serine/threonine kinase and helicase activities. An example is a REAP-predicted alternative exon in the SLK (serine/threonine kinase 2 gene that is differentially included in hESC, but skipped in NP as well as in other differentiated tissues. Lastly, comparative sequence analysis revealed conserved intronic cis-regulatory elements such as the FOX1/2 binding site GCAUG as being proximal to candidate AS exons, suggesting that FOX1/2 may participate in the regulation of AS in NP and hESC. In summary, a new methodology for exon array analysis was introduced

  10. Identifying colon cancer risk modules with better classification performance based on human signaling network.

    Science.gov (United States)

    Qu, Xiaoli; Xie, Ruiqiang; Chen, Lina; Feng, Chenchen; Zhou, Yanyan; Li, Wan; Huang, Hao; Jia, Xu; Lv, Junjie; He, Yuehan; Du, Youwen; Li, Weiguo; Shi, Yuchen; He, Weiming

    2014-10-01

    Identifying differences between normal and tumor samples from a modular perspective may help to improve our understanding of the mechanisms responsible for colon cancer. Many cancer studies have shown that signaling transduction and biological pathways are disturbed in disease states, and expression profiles can distinguish variations in diseases. In this study, we integrated a weighted human signaling network and gene expression profiles to select risk modules associated with tumor conditions. Risk modules as classification features by our method had a better classification performance than other methods, and one risk module for colon cancer had a good classification performance for distinguishing between normal/tumor samples and between tumor stages. All genes in the module were annotated to the biological process of positive regulation of cell proliferation, and were highly associated with colon cancer. These results suggested that these genes might be the potential risk genes for colon cancer. Copyright © 2013. Published by Elsevier Inc.

  11. A molecular systems approach to modelling human skin pigmentation: identifying underlying pathways and critical components.

    Science.gov (United States)

    Raghunath, Arathi; Sambarey, Awanti; Sharma, Neha; Mahadevan, Usha; Chandra, Nagasuma

    2015-04-29

    Ultraviolet radiations (UV) serve as an environmental stress for human skin, and result in melanogenesis, with the pigment melanin having protective effects against UV induced damage. This involves a dynamic and complex regulation of various biological processes that results in the expression of melanin in the outer most layers of the epidermis, where it can exert its protective effect. A comprehensive understanding of the underlying cross talk among different signalling molecules and cell types is only possible through a systems perspective. Increasing incidences of both melanoma and non-melanoma skin cancers necessitate the need to better comprehend UV mediated effects on skin pigmentation at a systems level, so as to ultimately evolve knowledge-based strategies for efficient protection and prevention of skin diseases. A network model for UV-mediated skin pigmentation in the epidermis was constructed and subjected to shortest path analysis. Virtual knock-outs were carried out to identify essential signalling components. We describe a network model for UV-mediated skin pigmentation in the epidermis. The model consists of 265 components (nodes) and 429 directed interactions among them, capturing the manner in which one component influences the other and channels information. Through shortest path analysis, we identify novel signalling pathways relevant to pigmentation. Virtual knock-outs or perturbations of specific nodes in the network have led to the identification of alternate modes of signalling as well as enabled determining essential nodes in the process. The model presented provides a comprehensive picture of UV mediated signalling manifesting in human skin pigmentation. A systems perspective helps provide a holistic purview of interconnections and complexity in the processes leading to pigmentation. The model described here is extensive yet amenable to expansion as new data is gathered. Through this study, we provide a list of important proteins essential

  12. Using citizen science data to identify the sensitivity of species to human land use.

    Science.gov (United States)

    Todd, Brian D; Rose, Jonathan P; Price, Steven J; Dorcas, Michael E

    2016-12-01

    Conservation practitioners must contend with an increasing array of threats that affect biodiversity. Citizen scientists can provide timely and expansive information for addressing these threats across large scales, but their data may contain sampling biases. We used randomization procedures to account for possible sampling biases in opportunistically reported citizen science data to identify species' sensitivities to human land use. We analyzed 21,044 records of 143 native reptile and amphibian species reported to the Carolina Herp Atlas from North Carolina and South Carolina between 1 January 1990 and 12 July 2014. Sensitive species significantly associated with natural landscapes were 3.4 times more likely to be legally protected or treated as of conservation concern by state resource agencies than less sensitive species significantly associated with human-dominated landscapes. Many of the species significantly associated with natural landscapes occurred primarily in habitats that had been nearly eradicated or otherwise altered in the Carolinas, including isolated wetlands, longleaf pine savannas, and Appalachian forests. Rare species with few reports were more likely to be associated with natural landscapes and 3.2 times more likely to be legally protected or treated as of conservation concern than species with at least 20 reported occurrences. Our results suggest that opportunistically reported citizen science data can be used to identify sensitive species and that species currently restricted primarily to natural landscapes are likely at greatest risk of decline from future losses of natural habitat. Our approach demonstrates the usefulness of citizen science data in prioritizing conservation and in helping practitioners address species declines and extinctions at large extents. © 2016 Society for Conservation Biology.

  13. Novel association strategy with copy number variation for identifying new risk Loci of human diseases.

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    Xianfeng Chen

    2010-08-01

    Full Text Available Copy number variations (CNV are important causal genetic variations for human disease; however, the lack of a statistical model has impeded the systematic testing of CNVs associated with disease in large-scale cohort.Here, we developed a novel integrated strategy to test CNV-association in genome-wide case-control studies. We converted the single-nucleotide polymorphism (SNP signal to copy number states using a well-trained hidden Markov model. We mapped the susceptible CNV-loci through SNP site-specific testing to cope with the physiological complexity of CNVs. We also ensured the credibility of the associated CNVs through further window-based CNV-pattern clustering. Genome-wide data with seven diseases were used to test our strategy and, in total, we identified 36 new susceptible loci that are associated with CNVs for the seven diseases: 5 with bipolar disorder, 4 with coronary artery disease, 1 with Crohn's disease, 7 with hypertension, 9 with rheumatoid arthritis, 7 with type 1 diabetes and 3 with type 2 diabetes. Fifteen of these identified loci were validated through genotype-association and physiological function from previous studies, which provide further confidence for our results. Notably, the genes associated with bipolar disorder converged in the phosphoinositide/calcium signaling, a well-known affected pathway in bipolar disorder, which further supports that CNVs have impact on bipolar disorder.Our results demonstrated the effectiveness and robustness of our CNV-association analysis and provided an alternative avenue for discovering new associated loci of human diseases.

  14. Immunochip analysis identifies association of the RAD50/IL13 region with human longevity.

    Science.gov (United States)

    Flachsbart, Friederike; Ellinghaus, David; Gentschew, Liljana; Heinsen, Femke-Anouska; Caliebe, Amke; Christiansen, Lene; Nygaard, Marianne; Christensen, Kaare; Blanché, Hélène; Deleuze, Jean-François; Derbois, Céline; Galan, Pilar; Büning, Carsten; Brand, Stephan; Peters, Anette; Strauch, Konstantin; Müller-Nurasyid, Martina; Hoffmann, Per; Nöthen, Markus M; Lieb, Wolfgang; Franke, Andre; Schreiber, Stefan; Nebel, Almut

    2016-06-01

    Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long-lived individuals (LLI) and 8919 younger controls. First, we performed a large-scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune-associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip-wide significant signal (PI mmunochip  = 7.01 × 10(-9) ) for the SNP rs2075650 in the TOMM40/APOE region, which has been previously described in the context of human longevity. To identify novel susceptibility loci, we selected 15 markers with PI mmunochip  association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant in a meta-analysis of the combined French and Danish data after adjusting for multiple testing. In a meta-analysis of all three samples, rs2706372 reached a P-value of PI mmunochip+Repl  = 5.42 × 10(-7) (OR = 1.20; 95% CI = 1.12-1.28). SNP rs2706372 is located in the extended RAD50/IL13 region. RAD50 seems a plausible longevity candidate due to its involvement in DNA repair and inflammation. Further studies are needed to identify the functional variant(s) that predispose(s) to a long and healthy life. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  15. Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology.

    Science.gov (United States)

    Levy, Daniel; Neuhausen, Susan L; Hunt, Steven C; Kimura, Masayuki; Hwang, Shih-Jen; Chen, Wei; Bis, Joshua C; Fitzpatrick, Annette L; Smith, Erin; Johnson, Andrew D; Gardner, Jeffrey P; Srinivasan, Sathanur R; Schork, Nicholas; Rotter, Jerome I; Herbig, Utz; Psaty, Bruce M; Sastrasinh, Malinee; Murray, Sarah S; Vasan, Ramachandran S; Province, Michael A; Glazer, Nicole L; Lu, Xiaobin; Cao, Xiaojian; Kronmal, Richard; Mangino, Massimo; Soranzo, Nicole; Spector, Tim D; Berenson, Gerald S; Aviv, Abraham

    2010-05-18

    Telomeres are engaged in a host of cellular functions, and their length is regulated by multiple genes. Telomere shortening, in the course of somatic cell replication, ultimately leads to replicative senescence. In humans, rare mutations in genes that regulate telomere length have been identified in monogenic diseases such as dyskeratosis congenita and idiopathic pulmonary fibrosis, which are associated with shortened leukocyte telomere length (LTL) and increased risk for aplastic anemia. Shortened LTL is observed in a host of aging-related complex genetic diseases and is associated with diminished survival in the elderly. We report results of a genome-wide association study of LTL in a consortium of four observational studies (n = 3,417 participants with LTL and genome-wide genotyping). SNPs in the regions of the oligonucleotide/oligosaccharide-binding folds containing one gene (OBFC1; rs4387287; P = 3.9 x 10(-9)) and chemokine (C-X-C motif) receptor 4 gene (CXCR4; rs4452212; P = 2.9 x 10(-8)) were associated with LTL at a genome-wide significance level (P a gene associated with LTL (P = 1.1 x 10(-5)). The identification of OBFC1 through genome-wide association as a locus for interindividual variation in LTL in the general population advances the understanding of telomere biology in humans and may provide insights into aging-related disorders linked to altered LTL dynamics.

  16. Fourier transform infrared microspectroscopy identifies early lineage commitment in differentiating human embryonic stem cells.

    Science.gov (United States)

    Heraud, Philip; Ng, Elizabeth S; Caine, Sally; Yu, Qing C; Hirst, Claire; Mayberry, Robyn; Bruce, Amanda; Wood, Bayden R; McNaughton, Don; Stanley, Edouard G; Elefanty, Andrew G

    2010-03-01

    Human ESCs (hESCs) are a valuable tool for the study of early human development and represent a source of normal differentiated cells for pharmaceutical and biotechnology applications and ultimately for cell replacement therapies. For all applications, it will be necessary to develop assays to validate the efficacy of hESC differentiation. We explored the capacity for FTIR spectroscopy, a technique that rapidly characterises cellular macromolecular composition, to discriminate mesendoderm or ectoderm committed cells from undifferentiated hESCs. Distinct infrared spectroscopic "signatures" readily distinguished hESCs from these early differentiated progeny, with bioinformatic models able to correctly classify over 97% of spectra. These data identify a role for FTIR spectroscopy as a new modality to complement conventional analyses of hESCs and their derivatives. FTIR spectroscopy has the potential to provide low-cost, automatable measurements for the quality control of stem and differentiated cells to be used in industry and regenerative medicine. Crown Copyright 2009. Published by Elsevier B.V. All rights reserved.

  17. Use of RUNX2 Expression to Identify Osteogenic Progenitor Cells Derived from Human Embryonic Stem Cells

    Science.gov (United States)

    Zou, Li; Kidwai, Fahad K.; Kopher, Ross A.; Motl, Jason; Kellum, Cory A.; Westendorf, Jennifer J.; Kaufman, Dan S.

    2015-01-01

    Summary We generated a RUNX2-yellow fluorescent protein (YFP) reporter system to study osteogenic development from human embryonic stem cells (hESCs). Our studies demonstrate the fidelity of YFP expression with expression of RUNX2 and other osteogenic genes in hESC-derived osteoprogenitor cells, as well as the osteogenic specificity of YFP signal. In vitro studies confirm that the hESC-derived YFP+ cells have similar osteogenic phenotypes to osteoprogenitor cells generated from bone-marrow mesenchymal stem cells. In vivo studies demonstrate the hESC-derived YFP+ cells can repair a calvarial defect in immunodeficient mice. Using the engineered hESCs, we monitored the osteogenic development and explored the roles of osteogenic supplements BMP2 and FGF9 in osteogenic differentiation of these hESCs in vitro. Taken together, this reporter system provides a novel system to monitor the osteogenic differentiation of hESCs and becomes useful to identify soluble agents and cell signaling pathways that mediate early stages of human bone development. PMID:25680477

  18. Use of RUNX2 Expression to Identify Osteogenic Progenitor Cells Derived from Human Embryonic Stem Cells

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    Li Zou

    2015-02-01

    Full Text Available We generated a RUNX2-yellow fluorescent protein (YFP reporter system to study osteogenic development from human embryonic stem cells (hESCs. Our studies demonstrate the fidelity of YFP expression with expression of RUNX2 and other osteogenic genes in hESC-derived osteoprogenitor cells, as well as the osteogenic specificity of YFP signal. In vitro studies confirm that the hESC-derived YFP+ cells have similar osteogenic phenotypes to osteoprogenitor cells generated from bone-marrow mesenchymal stem cells. In vivo studies demonstrate the hESC-derived YFP+ cells can repair a calvarial defect in immunodeficient mice. Using the engineered hESCs, we monitored the osteogenic development and explored the roles of osteogenic supplements BMP2 and FGF9 in osteogenic differentiation of these hESCs in vitro. Taken together, this reporter system provides a novel system to monitor the osteogenic differentiation of hESCs and becomes useful to identify soluble agents and cell signaling pathways that mediate early stages of human bone development.

  19. High throughput Screening to Identify Natural Human Monoamine Oxidase B Inhibitors

    Science.gov (United States)

    Mazzio, E; Deiab, S; Park, K; Soliman, KFA

    2012-01-01

    Age-related increase in monoamine oxidase B (MAO-B) may contribute to CNS neurodegenerative diseases. Moreover, MAO-B inhibitors are used in the treatment of idiopathic Parkinson disease as preliminary monotherapy or adjunct therapy with L-dopa. To date, meager natural sources of MAO-B inhibitors have been identified, and the relative strength, potency and rank of many plants relative to standard drugs such as Selegiline (L-deprenyl, Eldepryl) are not known. In this work, we developed and utilized a high throughput enzyme microarray format to screen and evaluate 905 natural product extracts (0.025–.7 mg/ml) to inhibit human MAO-B derived from BTI-TN-5B1-4 cells infected with recombinant baculovirus. The protein sequence of purified enzyme was confirmed using 1D gel electrophoresis-matrix assisted laser desorption ionization-time-of-flight-tandem mass spectroscopy, and enzyme activity was confirmed by [1] substrate conversion (3-mM benzylamine) to H202 and [2] benzaldehyde. Of the 905 natural extracts tested, the lowest IC50s [Comfrey, Bringraj, Skullcap, Kava-kava, Wild Indigo, Gentian and Green Tea. In conclusion, the data reflect relative potency information by rank of commonly used herbs and plants that contain human MAO-B inhibitory properties in their natural form. PMID:22887993

  20. Altered endoribonuclease activity of apurinic/apyrimidinic endonuclease 1 variants identified in the human population.

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    Wan Cheol Kim

    Full Text Available Apurinic/apyrimidinic endonuclease 1 (APE1 is the major mammalian enzyme in the DNA base excision repair pathway and cleaves the DNA phosphodiester backbone immediately 5' to abasic sites. APE1 also has 3'-5' DNA exonuclease and 3' DNA phosphodiesterase activities, and regulates transcription factor DNA binding through its redox regulatory function. The human APE1 has recently been shown to endonucleolytically cleave single-stranded regions of RNA. Towards understanding the biological significance of the endoribonuclease activity of APE1, we examined eight different amino acid substitution variants of APE1 previously identified in the human population. Our study shows that six APE1 variants, D148E, Q51H, I64V, G241R, R237A, and G306A, exhibit a 76-85% reduction in endoribonuclease activity against a specific coding region of the c-myc RNA, yet fully retain the ability to cleave apurinic/apyrimidinic DNA. We found that two APE1 variants, L104R and E126D, exhibit a unique RNase inhibitor-resistant endoribonuclease activity, where the proteins cleave c-myc RNA 3' of specific single-stranded guanosine residues. Expression of L104R and E126D APE1 variants in bacterial Origami cells leads to a 60-80% reduction in colony formation and a 1.5-fold increase in cell doubling time, whereas the other variants, which exhibit diminished endoribonuclease activity, had no effect. These data indicate that two human APE1 variants exhibit a unique endoribonuclease activity, which correlates with their ability to induce cytotoxicity or slow down growth in bacterial cells and supports the notion of their biological functionality.

  1. Red Assembly: the work remains

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    Leslie Witz

    Full Text Available This issue of Kronos is dedicated to Terry Flynn, assistant curator at the Ann Bryant Art Gallery, who was instrumental in the successful installing of 'Red Assembly' there in 2015. Friend, colleague, artist and inspiration. Hamba Kahle. The work that emerged from the encounter with Red, an art installation by Simon Gush and his collaborators, in the workshop 'Red Assembly', held in East London in August 2015, is assembled here in Kronos, the journal of southern African histories based at the University of the Western Cape, and previously in parallax, the cultural studies journal based at the University of Leeds published in May 2016. What is presented there and here is not simply more work, work that follows, or even additional works. Rather, it is the work that arises as a response to a question that structured our entire project: does Red, now also installed in these two journals, have the potential to call the discourse of history into question? This article responds to this question through several pairings: theft - gift; copy - rights; time - history; kronos - chronos. Here we identify a reversal in this installation of the gift into the commodity, and another with regard to conventional historical narratives which privilege the search for sources and origins. A difference between (the historian's search for origination and (the artist's originality becomes visible in a conversation between and over the historic and the artistic that does not simply try to rescue History by means of the work of art. It is in this sense that we invite the displacements, detours, and paths made possible through Simon Gush's Red, the 'Red Assembly' workshop and the work/gift of installation and parallaxing. To gesture beyond 'histories' is the provocation to which art is neither cause nor effect. Thinking with the work of art, that is, grasping thought in the working of art, has extended the sense of history's limit and the way the limit of history is

  2. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

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    Wouter Boomsma

    2016-02-01

    Full Text Available The ubiquitin-proteasome system targets misfolded proteins for degradation. Since the accumulation of such proteins is potentially harmful for the cell, their prompt removal is important. E3 ubiquitin-protein ligases mediate substrate ubiquitination by bringing together the substrate with an E2 ubiquitin-conjugating enzyme, which transfers ubiquitin to the substrate. For misfolded proteins, substrate recognition is generally delegated to molecular chaperones that subsequently interact with specific E3 ligases. An important exception is San1, a yeast E3 ligase. San1 harbors extensive regions of intrinsic disorder, which provide both conformational flexibility and sites for direct recognition of misfolded targets of vastly different conformations. So far, no mammalian ortholog of San1 is known, nor is it clear whether other E3 ligases utilize disordered regions for substrate recognition. Here, we conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology of their ordered regions, and did not capture the unique disorder patterns that encode the functional mechanism of San1. However, by searching specifically for key features of the San1 sequence, such as long regions of intrinsic disorder embedded with short stretches predicted to be suitable for substrate interaction, we identified several E3 ligases with these characteristics. Our initial analysis revealed that another remarkable trait of San1 is shared with several candidate E3 ligases: long stretches of complete lysine suppression, which in San1 limits auto-ubiquitination. We encode these characteristic features into a San1 similarity-score, and present a set of proteins that are plausible candidates as San1 counterparts in humans. In conclusion, our work

  3. Pathway Interaction Network Analysis Identifies Dysregulated Pathways in Human Monocytes Infected by Listeria monocytogenes

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    Wufeng Fan

    2017-01-01

    Full Text Available In our study, we aimed to extract dysregulated pathways in human monocytes infected by Listeria monocytogenes (LM based on pathway interaction network (PIN which presented the functional dependency between pathways. After genes were aligned to the pathways, principal component analysis (PCA was used to calculate the pathway activity for each pathway, followed by detecting seed pathway. A PIN was constructed based on gene expression profile, protein-protein interactions (PPIs, and cellular pathways. Identifying dysregulated pathways from the PIN was performed relying on seed pathway and classification accuracy. To evaluate whether the PIN method was feasible or not, we compared the introduced method with standard network centrality measures. The pathway of RNA polymerase II pretranscription events was selected as the seed pathway. Taking this seed pathway as start, one pathway set (9 dysregulated pathways with AUC score of 1.00 was identified. Among the 5 hub pathways obtained using standard network centrality measures, 4 pathways were the common ones between the two methods. RNA polymerase II transcription and DNA replication owned a higher number of pathway genes and DEGs. These dysregulated pathways work together to influence the progression of LM infection, and they will be available as biomarkers to diagnose LM infection.

  4. An integrative -omics approach to identify functional sub-networks in human colorectal cancer.

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    Rod K Nibbe

    2010-01-01

    Full Text Available Emerging evidence indicates that gene products implicated in human cancers often cluster together in "hot spots" in protein-protein interaction (PPI networks. Additionally, small sub-networks within PPI networks that demonstrate synergistic differential expression with respect to tumorigenic phenotypes were recently shown to be more accurate classifiers of disease progression when compared to single targets identified by traditional approaches. However, many of these studies rely exclusively on mRNA expression data, a useful but limited measure of cellular activity. Proteomic profiling experiments provide information at the post-translational level, yet they generally screen only a limited fraction of the proteome. Here, we demonstrate that integration of these complementary data sources with a "proteomics-first" approach can enhance the discovery of candidate sub-networks in cancer that are well-suited for mechanistic validation in disease. We propose that small changes in the mRNA expression of multiple genes in the neighborhood of a protein-hub can be synergistically associated with significant changes in the activity of that protein and its network neighbors. Further, we hypothesize that proteomic targets with significant fold change between phenotype and control may be used to "seed" a search for small PPI sub-networks that are functionally associated with these targets. To test this hypothesis, we select proteomic targets having significant expression changes in human colorectal cancer (CRC from two independent 2-D gel-based screens. Then, we use random walk based models of network crosstalk and develop novel reference models to identify sub-networks that are statistically significant in terms of their functional association with these proteomic targets. Subsequently, using an information-theoretic measure, we evaluate synergistic changes in the activity of identified sub-networks based on genome-wide screens of mRNA expression in CRC

  5. Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis

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    Sadlier Denise M

    2007-02-01

    Full Text Available Abstract Background Osteoporosis, a disease of decreased bone mineral density represents a significant and growing burden in the western world. Aging population structure and therapeutic use of glucocorticoids have contributed in no small way to the increase in the incidence of this disease. Despite substantial investigative efforts over the last number of years the exact molecular mechanism underpinning the initiation and progression of osteoporosis remain to be elucidated. This has meant that no significant advances in therapeutic strategies have emerged, with joint replacement surgery being the mainstay of treatment. Methods In this study we have used an integrated genomics profiling and computational biology based strategy to identify the key osteoblast genes and gene clusters whose expression is altered in response to dexamethasone exposure. Primary human osteoblasts were exposed to dexamethasone in vitro and microarray based transcriptome profiling completed. Results These studies identified approximately 500 osteoblast genes whose expression was altered. Functional characterization of the transcriptome identified developmental networks as being reactivated with 106 development associated genes found to be differentially regulated. Pathway reconstruction revealed coordinate alteration of members of the WNT signaling pathway, including frizzled-2, frizzled-7, DKK1 and WNT5B, whose differential expression in this setting was confirmed by real time PCR. Conclusion The WNT pathway is a key regulator of skeletogenesis as well as differentiation of bone cells. Reactivation of this pathway may lead to altered osteoblast activity resulting in decreased bone mineral density, the pathological hallmark of osteoporosis. The data herein lend weight to the hypothesis that alterations in developmental pathways drive the initiation and progression of osteoporosis.

  6. Human immune responses to H. pylori HLA Class II epitopes identified by immunoinformatic methods.

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    Songhua Zhang

    Full Text Available H. pylori persists in the human stomach over decades and promotes several adverse clinical sequelae including gastritis, peptic ulcers and gastric cancer that are linked to the induction and subsequent evasion of chronic gastric inflammation. Emerging evidence indicates that H. pylori infection may also protect against asthma and some other immune-mediated conditions through regulatory T cell effects outside the stomach. To characterize the complexity of the CD4+ T cell response generated during H. pylori infection, computational methods were previously used to generate a panel of 90 predicted epitopes conserved among H. pylori genomes that broadly cover HLA Class II diversity for maximum population coverage. Here, these sequences were tested individually for their ability to induce in vitro responses in peripheral blood mononuclear cells by interferon-γ ELISpot assay. The average number of spot-forming cells/million PBMCs was significantly elevated in H. pylori-infected subjects over uninfected persons. Ten of the 90 peptides stimulated IFN-γ secretion in the H. pylori-infected group only, whereas two out of the 90 peptides elicited a detectable IFN-γ response in the H. pylori-uninfected subjects but no response in the H. pylori-infected group. Cytokine ELISA measurements performed using in vitro PBMC culture supernatants demonstrated significantly higher levels of TNF-α, IL-2, IL-4, IL-6, IL-10, and TGF-β1 in the H. pylori-infected subjects, whereas IL-17A expression was not related to the subjects H. pylori-infection status. Our results indicate that the human T cell responses to these 90 peptides are generally increased in actively H. pylori-infected, compared with H. pylori-naïve, subjects. This information will improve understanding of the complex immune response to H. pylori, aiding rational epitope-driven vaccine design as well as helping identify other H. pylori epitopes with potentially immunoregulatory effects.

  7. Gene expression profiling identifies HOXB4 as a direct downstream target of GATA-2 in human CD34+ hematopoietic cells.

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    Tohru Fujiwara

    Full Text Available Aplastic anemia is characterized by a reduced hematopoietic stem cell number. Although GATA-2 expression was reported to be decreased in CD34-positive cells in aplastic anemia, many questions remain regarding the intrinsic characteristics of hematopoietic stem cells in this disease. In this study, we identified HOXB4 as a downstream target of GATA-2 based on expression profiling with human cord blood-derived CD34-positive cells infected with control or GATA-2 lentiviral shRNA. To confirm the functional link between GATA-2 and HOXB4, we conducted GATA-2 gain-of-function and loss-of-function experiments, and HOXB4 promoter analysis, including luciferase assay, in vitro DNA binding analysis and quantitative ChIP analysis, using K562 and CD34-positive cells. The analyses suggested that GATA-2 directly regulates HOXB4 expression through the GATA sequence in the promoter region. Furthermore, we assessed GATA-2 and HOXB4 expression in CD34-positive cells from patients with aplastic anemia (n = 10 and idiopathic thrombocytopenic purpura (n = 13, and demonstrated that the expression levels of HOXB4 and GATA-2 were correlated in these populations (r = 0.6573, p<0.01. Our results suggested that GATA-2 directly regulates HOXB4 expression in hematopoietic stem cells, which may play an important role in the development and/or progression of aplastic anemia.

  8. Multiple binding modes of ibuprofen in human serum albumin identified by absolute binding free energy calculations

    KAUST Repository

    Evoli, Stefania

    2016-11-10

    Human serum albumin possesses multiple binding sites and transports a wide range of ligands that include the anti-inflammatory drug ibuprofen. A complete map of the binding sites of ibuprofen in albumin is difficult to obtain in traditional experiments, because of the structural adaptability of this protein in accommodating small ligands. In this work, we provide a set of predictions covering the geometry, affinity of binding and protonation state for the pharmaceutically most active form (S-isomer) of ibuprofen to albumin, by using absolute binding free energy calculations in combination with classical molecular dynamics (MD) simulations and molecular docking. The most favorable binding modes correctly reproduce several experimentally identified binding locations, which include the two Sudlow\\'s drug sites (DS2 and DS1) and the fatty acid binding sites 6 and 2 (FA6 and FA2). Previously unknown details of the binding conformations were revealed for some of them, and formerly undetected binding modes were found in other protein sites. The calculated binding affinities exhibit trends which seem to agree with the available experimental data, and drastically degrade when the ligand is modeled in a protonated (neutral) state, indicating that ibuprofen associates with albumin preferentially in its charged form. These findings provide a detailed description of the binding of ibuprofen, help to explain a wide range of results reported in the literature in the last decades, and demonstrate the possibility of using simulation methods to predict ligand binding to albumin.

  9. Anxiolytic-Like Actions of Fatty Acids Identified in Human Amniotic Fluid

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    Rosa Isela García-Ríos

    2013-01-01

    Full Text Available Eight fatty acids (C12–C18 were previously identified in human amniotic fluid, colostrum, and milk in similar proportions but different amounts. Amniotic fluid is well known to be the natural environment for development in mammals. Interestingly, amniotic fluid and an artificial mixture of fatty acids contained in amniotic fluid produce similar anxiolytic-like actions in Wistar rats. We explored whether the lowest amount of fatty acids contained in amniotic fluid with respect to colostrum and milk produces such anxiolytic-like effects. Although a trend toward a dose-response effect was observed, only an amount of fatty acids that was similar to amniotic fluid fully mimicked the effect of diazepam (2 mg/kg, i.p. in the defensive burying test, an action devoid of effects on locomotor activity and motor coordination. Our results confirm that the amount of fatty acids contained in amniotic fluid is sufficient to produce anxiolytic-like effects, suggesting similar actions during intrauterine development.

  10. Resolving anatomical and functional structure in human brain organization: identifying mesoscale organization in weighted network representations.

    Science.gov (United States)

    Lohse, Christian; Bassett, Danielle S; Lim, Kelvin O; Carlson, Jean M

    2014-10-01

    Human brain anatomy and function display a combination of modular and hierarchical organization, suggesting the importance of both cohesive structures and variable resolutions in the facilitation of healthy cognitive processes. However, tools to simultaneously probe these features of brain architecture require further development. We propose and apply a set of methods to extract cohesive structures in network representations of brain connectivity using multi-resolution techniques. We employ a combination of soft thresholding, windowed thresholding, and resolution in community detection, that enable us to identify and isolate structures associated with different weights. One such mesoscale structure is bipartivity, which quantifies the extent to which the brain is divided into two partitions with high connectivity between partitions and low connectivity within partitions. A second, complementary mesoscale structure is modularity, which quantifies the extent to which the brain is divided into multiple communities with strong connectivity within each community and weak connectivity between communities. Our methods lead to multi-resolution curves of these network diagnostics over a range of spatial, geometric, and structural scales. For statistical comparison, we contrast our results with those obtained for several benchmark null models. Our work demonstrates that multi-resolution diagnostic curves capture complex organizational profiles in weighted graphs. We apply these methods to the identification of resolution-specific characteristics of healthy weighted graph architecture and altered connectivity profiles in psychiatric disease.

  11. Role of Anthropometric Dimensions of Human Body in Identifying Temperament in Traditional Persian Medicine

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    A Vahedi

    2016-07-01

    Full Text Available BACKGROUND AND OBJECTIVE: From the viewpoint of Traditional Persian Medicine (TPM, temperament of each person influences his physical and physiological properties such as body dimensions. The aim of this study is to review the reasons behind the diversity of human anthropometric measurements and their status in identifying temperament of people. METHODS: In this descriptive study, we searched online databases such as Sid.ir, PubMed, Scopus, Magiran.com and Google Scholar for Persian key words such as "Anthropometry", "ergonomics" and "temperament" and their English equivalent. Authentic TPM books such as "The Canon of Medicine" by Avicenna, "Complete Book of the Medical Art" by al-Majusi, "al-Mansouri fi al-Tibb" (The book on medicine dedicated to al-Mansur by Zakariya al-Razi, " Kholasa't ol Hikma" (summary of wisdom by Aghili Khorasani, “Zakhireh kharazmshahi”(The treasure of Kharazm Shah by Ismail Jurjani and "Bahr al-jawahir" (sea jewels were also studied. FINDINGS: Results of the study demonstrated that there is a direct relationship between weight gain, BMI and dimensions of soft tissue which are primarily signs of obesity and fat gain and cardiovascular diseases and diabetes. Since increase in the aforementioned indices can be a sign of coldness and wetness of temperament, one can argue that people with cold and wet temperament are more susceptible to such diseases. In references of TPM, temperament is mentioned as an agent that changes body dimensions and among the indices that identify temperament, "shape of organs" and "physique" is related to anatomic dimensions of body and obesity and thinness condition, receptively. Magnitude of chest and other organs is a sign of hotness; thinness is a sign of dryness; dominance of muscle tissue is a sign of hotness and wetness and dominance of adipose tissue is a sign of coldness and wetness of temperament. CONCLUSION: According to the results of the present study, variety of anthropometric

  12. Integration of mouse and human genome-wide association data identifies KCNIP4 as an asthma gene

    NARCIS (Netherlands)

    Himes, Blanca E.; Sheppard, Keith; Berndt, Annerose; Leme, Adriana S.; Myers, Rachel A.; Gignoux, Christopher R.; Levin, Albert M.; Gauderman, W. James; Yang, James J.; Mathias, Rasika A.; Romieu, Isabelle; Torgerson, Dara G.; Roth, Lindsey A.; Huntsman, Scott; Eng, Celeste; Klanderman, Barbara; Ziniti, John; Senter-Sylvia, Jody; Szefler, Stanley J.; Lemanske, Robert F.; Zeiger, Robert S.; Strunk, Robert C.; Martinez, Fernando D.; Boushey, Homer; Chinchilli, Vernon M.; Israel, Elliot; Mauger, David; Koppelman, Gerard H.; Postma, Dirkje S.; Nieuwenhuis, Maartje A. E.; Vonk, Judith M.; Lima, John J.; Irvin, Charles G.; Peters, Stephen P.; Kubo, Michiaki; Tamari, Mayumi; Nakamura, Yusuke; Litonjua, Augusto A.; Tantisira, Kelan G.; Raby, Benjamin A.; Bleecker, Eugene R.; Meyers, Deborah A.; London, Stephanie J.; Barnes, Kathleen C.; Gilliland, Frank D.; Williams, L. Keoki; Burchard, Esteban G.; Nicolae, Dan L.; Ober, Carole; DeMeo, Dawn L.; Silverman, Edwin K.; Paigen, Beverly; Churchill, Gary; Shapiro, Steve D.; Weiss, Scott

    2013-01-01

    Asthma is a common chronic respiratory disease characterized by airway hyperresponsiveness (AHR). The genetics of asthma have been widely studied in mouse and human, and homologous genomic regions have been associated with mouse AHR and human asthma-related phenotypes. Our goal was to identify

  13. SMART POINT CLOUD: DEFINITION AND REMAINING CHALLENGES

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    F. Poux

    2016-10-01

    Full Text Available Dealing with coloured point cloud acquired from terrestrial laser scanner, this paper identifies remaining challenges for a new data structure: the smart point cloud. This concept arises with the statement that massive and discretized spatial information from active remote sensing technology is often underused due to data mining limitations. The generalisation of point cloud data associated with the heterogeneity and temporality of such datasets is the main issue regarding structure, segmentation, classification, and interaction for an immediate understanding. We propose to use both point cloud properties and human knowledge through machine learning to rapidly extract pertinent information, using user-centered information (smart data rather than raw data. A review of feature detection, machine learning frameworks and database systems indexed both for mining queries and data visualisation is studied. Based on existing approaches, we propose a new 3-block flexible framework around device expertise, analytic expertise and domain base reflexion. This contribution serves as the first step for the realisation of a comprehensive smart point cloud data structure.

  14. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    NARCIS (Netherlands)

    Adams, Hieab H H; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura M E; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; Braber, Anouk Den; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco J C; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Pol, Hilleke E Hulshoff; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, W T; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic J A; Van Duijn, Cornelia M; Van Haren, Neeltje E M; Van T Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton J M; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously

  15. Investigating Salmonella Eko from Various Sources in Nigeria by Whole Genome Sequencing to Identify the Source of Human Infections

    DEFF Research Database (Denmark)

    Leekitcharoenphon, Pimlapas; Raufu, Ibrahim; Thorup Nielsen, Mette

    2016-01-01

    Twenty-six Salmonella enterica serovar Eko isolated from various sources in Nigeria were investigated by whole genome sequencing to identify the source of human infections. Diversity among the isolates was observed and camel and cattle were identified as the primary reservoirs and the most likely...

  16. Analysis of arsenic and mercury content in human remains of the 16th and 17th centuries from Moscow Kremlin necropolises by neutron activation analysis at the IREN facility and the IBR-2 reactor FLNP JINR

    Science.gov (United States)

    Panova, T. D.; Dmitriev, A. Yu.; Borzakov, S. B.; Hramco, C.

    2018-01-01

    A neutron activation analysis (NAA) of three samples of human remains of the 16th and 17th centuries from the necropolises of the Moscow Kremlin has been carried out at FLNP JINR. The samples were irradiated at two facilities: the IREN source of resonance neutrons and the IBR-2 reactor. Spectra of the induced activity of the irradiated samples were measured by using the automatic measurement system developed at the Frank Laboratory of Neutron Physics (FLNP) of the Joint Institute for Nuclear Research (JINR). This system consists of a high-purity germanium detector with spectrometric electronics, a sample changer, and control software. Mass fraction of arsenic, mercury, and some other elements were calculated using two NAA methods—relative and absolute. The obtained values confirm the fact of acute mercury poisoning of Anastasia Romanovna, the first wife of Tsar Ivan Vasil'evich the Terrible, the first Russian Tsarina (died in 1560). High levels of mercury were detected in the bone remains of Tsarevich Ivan Ivanovich (died in 1581), the son of Tsar Ivan the Terrible, and Prince Mikhail Vasil'evich Skopin-Shuiskii (died in 1610). The results provide an opportunity to introduce into scientific circulation the exact values of mass fraction of mercury, arsenic, and other elements in the samples taken from the burials of the Russian historical figures of the second half of 16th-early 17th century.

  17. Qualitative and quantitative analysis of arsenic and mercury in human remains of the XVI-XVII centuries from the Moscow Kremlin necropolises by neutron activation analysis at the IREN facility and the IBR-2 reactor of FLNP, JINR

    International Nuclear Information System (INIS)

    Panova, T.D.; Dmitriev, A.Yu.; Borzakov, S.B.; Khramko, K.

    2017-01-01

    The neutron activation analysis (NAA) of three samples of human remains of the XVI-XVII centuries from the necropolises of the Moscow Kremlin has been carried out at FLNP JINR. The samples were irradiated at two facilities: at the IREN source of resonance neutrons and at the IBR-2 reactor. Spectra of induced activity of the irradiated samples were measured by using the automatic measurement system developed at FLNP JINR. This system consists of a high-purity germanium detector with spectrometric electronics, a sample changer, and a control software. Mass fractions of arsenic, mercury and other elements were calculated by relative and absolute NAA methods. The obtained values confirmed the fact of an acute mercury poisoning of the first wife of Tsar Ivan Vasilievich the Terrible - Tsarina Anastasia Romanovna. Increased mercury content was detected in the bone remains of the son of Tsar Ivan the Terrible, Tsarevich Ivan Ivanovich, and Prince M. V. Skopin-Shuisky. The obtained results allow us to introduce into scientific circulation the exact values of mass fraction of mercury, arsenic and some other elements in the samples from the graves of Russian historical figures of the second half of XVI - early XVII centuries. [ru

  18. Identifying Functional Requirements for Flexible Airspace Management Concept Using Human-In-The-Loop Simulations

    Science.gov (United States)

    Lee, Paul U.; Bender, Kim; Pagan, Danielle

    2011-01-01

    Flexible Airspace Management (FAM) is a mid- term Next Generation Air Transportation System (NextGen) concept that allows dynamic changes to airspace configurations to meet the changes in the traffic demand. A series of human-in-the-loop (HITL) studies have identified procedures and decision support requirements needed to implement FAM. This paper outlines a suggested FAM procedure and associated decision support functionality based on these HITL studies. A description of both the tools used to support the HITLs and the planned NextGen technologies available in the mid-term are presented and compared. The mid-term implementation of several NextGen capabilities, specifically, upgrades to the Traffic Management Unit (TMU), the initial release of an en route automation system, the deployment of a digital data communication system, a more flexible voice communications network, and the introduction of a tool envisioned to manage and coordinate networked ground systems can support the implementation of the FAM concept. Because of the variability in the overall deployment schedule of the mid-term NextGen capabilities, the dependency of the individual NextGen capabilities are examined to determine their impact on a mid-term implementation of FAM. A cursory review of the different technologies suggests that new functionality slated for the new en route automation system is a critical enabling technology for FAM, as well as the functionality to manage and coordinate networked ground systems. Upgrades to the TMU are less critical but important nonetheless for FAM to be fully realized. Flexible voice communications network and digital data communication system could allow more flexible FAM operations but they are not as essential.

  19. Detecting new microRNAs in human osteoarthritic chondrocytes identifies miR-3085 as a human, chondrocyte-selective, microRNA

    OpenAIRE

    Crowe, N.; Swingler, T.E.; Le, L.T.T.; Barter, M.J.; Wheeler, G.; Pais, H.; Donell, S.T.; Young, D.A.; Dalmay, T.; Clark, I.M.

    2016-01-01

    Summary Objective To use deep sequencing to identify novel microRNAs (miRNAs) in human osteoarthritic cartilage which have a functional role in chondrocyte phenotype or function. Design A small RNA library was prepared from human osteoarthritic primary chondrocytes using in-house adaptors and analysed by Illumina sequencing. Novel candidate miRNAs were validated by northern blot and qRT-PCR. Expression was measured in cartilage models. Targets of novel candidates were identified by microarray...

  20. COMPETITIVE METAGENOMIC DNA HYBRIDIZATION IDENTIFIES HOST-SPECIFIC GENETIC MARKERS IN HUMAN FECAL MICROBIAL COMMUNITIES

    Science.gov (United States)

    Although recent technological advances in DNA sequencing and computational biology now allow scientists to compare entire microbial genomes, the use of these approaches to discern key genomic differences between natural microbial communities remains prohibitively expensive for mo...

  1. Using a Functional Architecture to Identify Human-Automation Trust Needs and Design Requirements

    Science.gov (United States)

    2016-12-01

    example, Parasuraman cites a study performed by Muir (1988) on the use of an automated aid to control a simulated beverage manufacturing plant (1997, 236...human trust are developed from a literature review covering theory and empirical studies that have investigated the importance of human trust in...The factors that affect human trust are developed from a literature review covering theory and empirical studies that have investigated the

  2. NEW METHODOLOGY FOR IDENTIFYING POTENTIAL HUMAN BIOMARKERS BY COLLECTION AND CONCENTRATION OF EXHALED BREATH CONDENSATE

    Science.gov (United States)

    In many studies of human exposure, the measurement of pollutant chemicals in the environment (air, water, food, soil, etc.) is being supplemented by their additional measurement in biological media such as human breath, blood, and urine. This allows an unambiguous confirmation...

  3. Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations.

    Science.gov (United States)

    Philippeos, Christina; Telerman, Stephanie B; Oulès, Bénédicte; Pisco, Angela O; Shaw, Tanya J; Elgueta, Raul; Lombardi, Giovanna; Driskell, Ryan R; Soldin, Mark; Lynch, Magnus D; Watt, Fiona M

    2018-04-01

    Previous studies have shown that mouse dermis is composed of functionally distinct fibroblast lineages. To explore the extent of fibroblast heterogeneity in human skin, we used a combination of comparative spatial transcriptional profiling of human and mouse dermis and single-cell transcriptional profiling of human dermal fibroblasts. We show that there are at least four distinct fibroblast populations in adult human skin, not all of which are spatially segregated. We define markers permitting their isolation and show that although marker expression is lost in culture, different fibroblast subpopulations retain distinct functionality in terms of Wnt signaling, responsiveness to IFN-γ, and ability to support human epidermal reconstitution when introduced into decellularized dermis. These findings suggest that ex vivo expansion or in vivo ablation of specific fibroblast subpopulations may have therapeutic applications in wound healing and diseases characterized by excessive fibrosis. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Why Agricultural Educators Remain in the Classroom

    Science.gov (United States)

    Crutchfield, Nina; Ritz, Rudy; Burris, Scott

    2013-01-01

    The purpose of this study was to identify and describe factors that are related to agricultural educator career retention and to explore the relationships between work engagement, work-life balance, occupational commitment, and personal and career factors as related to the decision to remain in the teaching profession. The target population for…

  5. Fish remains and humankind: part two

    Directory of Open Access Journals (Sweden)

    Andrew K G Jones

    1998-07-01

    Full Text Available The significance of aquatic resources to past human groups is not adequately reflected in the published literature - a deficiency which is gradually being acknowledged by the archaeological community world-wide. The publication of the following three papers goes some way to redress this problem. Originally presented at an International Council of Archaeozoology (ICAZ Fish Remains Working Group meeting in York, U.K. in 1987, these papers offer clear evidence of the range of interest in ancient fish remains across the world. Further papers from the York meeting were published in Internet Archaeology 3 in 1997.

  6. Identifying areas of high risk of human exposure to coccidioidomycosis in Texas using serology data from dogs.

    Science.gov (United States)

    Gautam, R; Srinath, I; Clavijo, A; Szonyi, B; Bani-Yaghoub, M; Park, S; Ivanek, R

    2013-03-01

    Coccidioidomycosis or Valley Fever (VF) is an emerging soil-borne fungal zoonosis affecting humans and animals. Most non-human cases of VF are found in dogs, which we hypothesize may serve as sentinels for estimating the human exposure risk. The objective of this study is to use the spatial and temporal distribution and clusters of dogs seropositive for VF to define the geographic area in Texas where VF is endemic, and thus presents a higher risk of exposure to humans. The included specimens were seropositive dogs tested at a major diagnostic laboratory between 1999 and 2009. Data were aggregated by zip code and smoothed by empirical Bayesian estimation to develop an isopleth map of VF seropositive rates using kriging. Clusters of seropositive dogs were identified using the spatial scan test. Both the isopleth map and the scan test identified an area with a high rate of VF-seropositive dogs in the western and southwestern parts of Texas (relative risk = 31). This location overlapped an area that was previously identified as a potential endemic region based on human surveys. Together, these data suggest that dogs may serve as sentinels for estimating the risk of human exposure to VF. © 2012 Blackwell Verlag GmbH.

  7. Identifying Spatial Units of Human Occupation in the Brazilian Amazon Using Landsat and CBERS Multi-Resolution Imagery

    OpenAIRE

    Dal’Asta, Ana Paula; Brigatti, Newton; Amaral, Silvana; Escada, Maria Isabel Sobral; Monteiro, Antonio Miguel Vieira

    2012-01-01

    Every spatial unit of human occupation is part of a network structuring an extensive process of urbanization in the Amazon territory. Multi-resolution remote sensing data were used to identify and map human presence and activities in the Sustainable Forest District of Cuiabá-Santarém highway (BR-163), west of Pará, Brazil. The limits of spatial units of human occupation were mapped based on digital classification of Landsat-TM5 (Thematic Mapper 5) image (30m spatial resolution). High-spatial-...

  8. Changes in dietary practices and social organization during the pivotal late iron age period in Norway (AD 550-1030): isotope analyses of Merovingian and Viking Age human remains.

    Science.gov (United States)

    Naumann, Elise; Price, T Douglas; Richards, Michael P

    2014-11-01

    Human remains representing 33 individuals buried along the coast in northern Norway were analyzed for diet composition using collagen stable carbon and nitrogen isotope analysis. Where possible, both teeth and bone were included to investigate whether there were dietary changes from childhood to adulthood. A general shift was documented from the Merovingian Age 550-800 AD to the Viking Age AD 800-1050 (VA), with a heavier reliance on marine diet in the VA. Dietary life history data show that 15 individuals changed their diets through life with 11 of these having consumed more marine foods in the later years of life. In combination with (87) Sr/(86) Sr data, it is argued that at least six individuals possibly originated from inland areas and then moved to the coastal region where they were eventually interred. The trend is considered in relation to the increasing expansion of the marine fishing industry at this time, and it is suggested that results from isotope analyses reflect the expanding production and export of stockfish in this region. © 2014 Wiley Periodicals, Inc.

  9. Unique features of a global human ectoparasite identified through sequencing of the bed bug genome.

    Science.gov (United States)

    Benoit, Joshua B; Adelman, Zach N; Reinhardt, Klaus; Dolan, Amanda; Poelchau, Monica; Jennings, Emily C; Szuter, Elise M; Hagan, Richard W; Gujar, Hemant; Shukla, Jayendra Nath; Zhu, Fang; Mohan, M; Nelson, David R; Rosendale, Andrew J; Derst, Christian; Resnik, Valentina; Wernig, Sebastian; Menegazzi, Pamela; Wegener, Christian; Peschel, Nicolai; Hendershot, Jacob M; Blenau, Wolfgang; Predel, Reinhard; Johnston, Paul R; Ioannidis, Panagiotis; Waterhouse, Robert M; Nauen, Ralf; Schorn, Corinna; Ott, Mark-Christoph; Maiwald, Frank; Johnston, J Spencer; Gondhalekar, Ameya D; Scharf, Michael E; Peterson, Brittany F; Raje, Kapil R; Hottel, Benjamin A; Armisén, David; Crumière, Antonin Jean Johan; Refki, Peter Nagui; Santos, Maria Emilia; Sghaier, Essia; Viala, Sèverine; Khila, Abderrahman; Ahn, Seung-Joon; Childers, Christopher; Lee, Chien-Yueh; Lin, Han; Hughes, Daniel S T; Duncan, Elizabeth J; Murali, Shwetha C; Qu, Jiaxin; Dugan, Shannon; Lee, Sandra L; Chao, Hsu; Dinh, Huyen; Han, Yi; Doddapaneni, Harshavardhan; Worley, Kim C; Muzny, Donna M; Wheeler, David; Panfilio, Kristen A; Vargas Jentzsch, Iris M; Vargo, Edward L; Booth, Warren; Friedrich, Markus; Weirauch, Matthew T; Anderson, Michelle A E; Jones, Jeffery W; Mittapalli, Omprakash; Zhao, Chaoyang; Zhou, Jing-Jiang; Evans, Jay D; Attardo, Geoffrey M; Robertson, Hugh M; Zdobnov, Evgeny M; Ribeiro, Jose M C; Gibbs, Richard A; Werren, John H; Palli, Subba R; Schal, Coby; Richards, Stephen

    2016-02-02

    The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host-symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human-bed bug and symbiont-bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.

  10. And the Dead Remain Behind

    Directory of Open Access Journals (Sweden)

    Peter Read

    2013-08-01

    Full Text Available In most cultures the dead and their living relatives are held in a dialogic relationship. The dead have made it clear, while living, what they expect from their descendants. The living, for their part, wish to honour the tombs of their ancestors; at the least, to keep the graves of the recent dead from disrepair. Despite the strictures, the living can fail their responsibilities, for example, by migration to foreign countries. The peripatetic Chinese are one of the few cultures able to overcome the dilemma of the wanderer or the exile. With the help of a priest, an Australian Chinese migrant may summon the soul of an ancestor from an Asian grave to a Melbourne temple, where the spirit, though removed from its earthly vessel, will rest and remain at peace. Amongst cultures in which such practices are not culturally appropriate, to fail to honour the family dead can be exquisitely painful. Violence is the cause of most failure.

  11. Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data

    OpenAIRE

    REN, ZHONGLU; WANG, WENHUI; LI, JINMING

    2015-01-01

    Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristi...

  12. Identifying the Learning Styles and Instructional Tool Preferences of Beginning Food Science and Human Nutrition Majors

    Science.gov (United States)

    Bohn, D. M.; Rasmussen, C. N.; Schmidt, S. J.

    2004-01-01

    Learning styles vary among individuals, and understanding which instructional tools certain learning styles prefer can be utilized to enhance student learning. Students in the introductory Food Science and Human Nutrition course (FSHN 101), taught at the Univ. of Illinois at Urbana-Champaign, were asked to complete Gregorc's Learning Style…

  13. Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species

    Science.gov (United States)

    Semple, Bridgette D.; Blomgren, Klas; Gimlin, Kayleen; Ferriero, Donna M.; Noble-Haeusslein, Linda J.

    2013-01-01

    Hypoxic-ischemic and traumatic brain injuries are leading causes of long-term mortality and disability in infants and children. Although several preclinical models using rodents of different ages have been developed, species differences in the timing of key brain maturation events can render comparisons of vulnerability and regenerative capacities difficult to interpret. Traditional models of developmental brain injury have utilized rodents at postnatal day 7–10 as being roughly equivalent to a term human infant, based historically on the measurement of post-mortem brain weights during the 1970s. Here we will examine fundamental brain development processes that occur in both rodents and humans, to delineate a comparable time course of postnatal brain development across species. We consider the timing of neurogenesis, synaptogenesis, gliogenesis, oligodendrocyte maturation and age-dependent behaviors that coincide with developmentally regulated molecular and biochemical changes. In general, while the time scale is considerably different, the sequence of key events in brain maturation is largely consistent between humans and rodents. Further, there are distinct parallels in regional vulnerability as well as functional consequences in response to brain injuries. With a focus on developmental hypoxicischemic encephalopathy and traumatic brain injury, this review offers guidelines for researchers when considering the most appropriate rodent age for the developmental stage or process of interest to approximate human brain development. PMID:23583307

  14. Mining Human Biomonitoring Data to Identify Prevalent Chemical Mixtures (SOT abstract)

    Science.gov (United States)

    Through food, water, air, and consumer products, humans are exposed to tens of thousands of environmental chemicals, and most of these have not been evaluated to determine their potential toxicities. In recent years, high-throughput screening (HTS) methods have been developed tha...

  15. Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage

    Czech Academy of Sciences Publication Activity Database

    Amps, K.; Andrews, P.W.; Anyfantis, G.; Armstrong, L.; Avery, S.; Baharvand, H.; Baker, J.; Baker, D.; Munoz, M. N.; Beil, S.; Benvenisty, N.; Ben-Yosef, D.; Biancotti, J. C.; Bosman, A.; Brena, R. M.; Brison, D.; Caisander, G.; Camarasa, M. V.; Chen, J. M.; Chiao, E.; Choi, Y. M.; Choo, E.; Collins, D.; Colman, A.; Crook, J. M.; Daley, G. Q.; Dalton, A.; De Sousa, P. A.; Denning, C.; Downie, J.; Dvořák, P.; Hampl, Aleš

    2011-01-01

    Roč. 29, č. 12 (2011), s. 1132-1144 ISSN 1087-0156 Institutional research plan: CEZ:AV0Z50390703 Keywords : comparative genomic hybridization * copy number variation * human es cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 23.268, year: 2011

  16. Recurrent chimeric RNAs enriched in human prostate cancer identified by deep sequencing

    Science.gov (United States)

    Kannan, Kalpana; Wang, Liguo; Wang, Jianghua; Ittmann, Michael M.; Li, Wei; Yen, Laising

    2011-01-01

    Transcription-induced chimeric RNAs, possessing sequences from different genes, are expected to increase the proteomic diversity through chimeric proteins or altered regulation. Despite their importance, few studies have focused on chimeric RNAs especially regarding their presence/roles in human cancers. By deep sequencing the transcriptome of 20 human prostate cancer and 10 matched benign prostate tissues, we obtained 1.3 billion sequence reads, which led to the identification of 2,369 chimeric RNA candidates. Chimeric RNAs occurred in significantly higher frequency in cancer than in matched benign samples. Experimental investigation of a selected 46 set led to the confirmation of 32 chimeric RNAs, of which 27 were highly recurrent and previously undescribed in prostate cancer. Importantly, a subset of these chimeras was present in prostate cancer cell lines, but not detectable in primary human prostate epithelium cells, implying their associations with cancer. These chimeras contain discernable 5′ and 3′ splice sites at the RNA junction, indicating that their formation is mediated by splicing. Their presence is also largely independent of the expression of parental genes, suggesting that other factors are involved in their production and regulation. One chimera, TMEM79-SMG5, is highly differentially expressed in human cancer samples and therefore a potential biomarker. The prevalence of chimeric RNAs may allow the limited number of human genes to encode a substantially larger number of RNAs and proteins, forming an additional layer of cellular complexity. Together, our results suggest that chimeric RNAs are widespread, and increased chimeric RNA events could represent a unique class of molecular alteration in cancer. PMID:21571633

  17. PUTATIVE CREATINE KINASE M-ISOFORM IN HUMAN SPERM IS IDENTIFIED AS THE 70-KILODALTON HEAT SHOCK PROTEIN HSPA2

    Science.gov (United States)

    THE PUTATIVE CREATINE KINASE M-ISOFORM IN HUMAN SPERM IS IDENTIFIED AS THE 70 kDa HEAT SHOCK PROTEIN HSPA2* Gabor Huszar1, Kathryn Stone2, David Dix3 and Lynne Vigue11The Sperm Physiology Laboratory, Department of Obstetrics and Gynecology, 2 W.M. Keck Foundatio...

  18. Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Philip W. Brownjohn

    2017-04-01

    Full Text Available Summary: Human stem cell models have the potential to provide platforms for phenotypic screens to identify candidate treatments and cellular pathways involved in the pathogenesis of neurodegenerative disorders. Amyloid precursor protein (APP processing and the accumulation of APP-derived amyloid β (Aβ peptides are key processes in Alzheimer's disease (AD. We designed a phenotypic small-molecule screen to identify modulators of APP processing in trisomy 21/Down syndrome neurons, a complex genetic model of AD. We identified the avermectins, commonly used as anthelmintics, as compounds that increase the relative production of short Aβ peptides at the expense of longer, potentially more toxic peptides. Further studies demonstrated that this effect is not due to an interaction with the core γ-secretase responsible for Aβ production. This study demonstrates the feasibility of phenotypic drug screening in human stem cell models of Alzheimer-type dementia, and points to possibilities for indirectly modulating APP processing, independently of γ-secretase modulation. : In this article, Livesey and colleagues perform a phenotypic drug screen in a human stem cell model of Alzheimer's disease. The anthelminthic avermectins are identified as a family of compounds that increase the production of short Aβ peptides over longer more toxic Aβ forms. The effect is analogous to existing γ-secretase modulators, but is independent of the core γ-secretase complex. Keywords: neural stem cells, Alzheimer's disease, phenotypic screening, iPSCs, human neurons, dementia, Down syndrome, amyloid beta, ivermectin, selamectin

  19. Green business will remain green

    International Nuclear Information System (INIS)

    Marcan, P.

    2008-01-01

    It all started with two words. Climate change. The carbon dioxide trading scheme, which was the politicians' idea on solving the number one global problem, followed. Four years ago, when the project was begun, there was no data for project initiation. Quotas for polluters mainly from energy production and other energy demanding industries were distributed based on spreadsheets, maximum output and expected future development of economies. Slovak companies have had a chance to profit from these arrangements since 2005. Many of them took advantage of the situation and turned the excessive quotas into an extraordinary profit which often reached hundreds of million Sk. The fact that the price of free quotas offered for sale dropped basically to 0 in 2006 only proved that the initial distribution was too generous. And the market reacted to the first official measurements of emissions. Slovak companies also contributed to this development. However, when planning the maximum emission volumes for 2008-2012 period, in spite of the fact that actual data were available, their expectations were not realistic. A glance at the figures in the proposal of the Ministry of Environment is sufficient to realize that there will be no major change in the future. And so for many Slovak companies business with a green future will remain green for the next five years. The state decided to give to selected companies even more free space as far as emissions are concerned. The most privileged companies can expect quotas increased by tens of percent. (author)

  20. Unique features of a global human ectoparasite identified through sequencing of the bed bug genome

    Science.gov (United States)

    Benoit, Joshua B.; Adelman, Zach N.; Reinhardt, Klaus; Dolan, Amanda; Poelchau, Monica; Jennings, Emily C.; Szuter, Elise M.; Hagan, Richard W.; Gujar, Hemant; Shukla, Jayendra Nath; Zhu, Fang; Mohan, M.; Nelson, David R.; Rosendale, Andrew J.; Derst, Christian; Resnik, Valentina; Wernig, Sebastian; Menegazzi, Pamela; Wegener, Christian; Peschel, Nicolai; Hendershot, Jacob M.; Blenau, Wolfgang; Predel, Reinhard; Johnston, Paul R.; Ioannidis, Panagiotis; Waterhouse, Robert M.; Nauen, Ralf; Schorn, Corinna; Ott, Mark-Christoph; Maiwald, Frank; Johnston, J. Spencer; Gondhalekar, Ameya D.; Scharf, Michael E.; Peterson, Brittany F.; Raje, Kapil R.; Hottel, Benjamin A.; Armisén, David; Crumière, Antonin Jean Johan; Refki, Peter Nagui; Santos, Maria Emilia; Sghaier, Essia; Viala, Sèverine; Khila, Abderrahman; Ahn, Seung-Joon; Childers, Christopher; Lee, Chien-Yueh; Lin, Han; Hughes, Daniel S. T.; Duncan, Elizabeth J.; Murali, Shwetha C.; Qu, Jiaxin; Dugan, Shannon; Lee, Sandra L.; Chao, Hsu; Dinh, Huyen; Han, Yi; Doddapaneni, Harshavardhan; Worley, Kim C.; Muzny, Donna M.; Wheeler, David; Panfilio, Kristen A.; Vargas Jentzsch, Iris M.; Vargo, Edward L.; Booth, Warren; Friedrich, Markus; Weirauch, Matthew T.; Anderson, Michelle A. E.; Jones, Jeffery W.; Mittapalli, Omprakash; Zhao, Chaoyang; Zhou, Jing-Jiang; Evans, Jay D.; Attardo, Geoffrey M.; Robertson, Hugh M.; Zdobnov, Evgeny M.; Ribeiro, Jose M. C.; Gibbs, Richard A.; Werren, John H.; Palli, Subba R.; Schal, Coby; Richards, Stephen

    2016-01-01

    The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite. PMID:26836814

  1. Human sewage identified as likely source of white pox disease of the threatened Caribbean elkhorn coral, Acropora palmata.

    Science.gov (United States)

    Sutherland, Kathryn Patterson; Porter, James W; Turner, Jeffrey W; Thomas, Brian J; Looney, Erin E; Luna, Trevor P; Meyers, Meredith K; Futch, J Carrie; Lipp, Erin K

    2010-05-01

    Caribbean elkhorn coral, Acropora palmata, has been decimated in recent years, resulting in the listing of this species as threatened under the United States Endangered Species Act. A major contributing factor in the decline of this iconic species is white pox disease. In 2002, we identified the faecal enterobacterium, Serratia marcescens, as an etiological agent for white pox. During outbreaks in 2003 a unique strain of S. marcescens was identified in both human sewage and white pox lesions. This strain (PDR60) was also identified from corallivorious snails (Coralliophila abbreviata), reef water, and two non-acroporid coral species, Siderastrea siderea and Solenastrea bournoni. Identification of PDR60 in sewage, diseased Acropora palmata and other reef invertebrates within a discrete time frame suggests a causal link between white pox and sewage contamination on reefs and supports the conclusion that humans are a likely source of this disease.

  2. An integrative analysis of reprogramming in human isogenic system identified a clone selection criterion.

    Science.gov (United States)

    Shutova, Maria V; Surdina, Anastasia V; Ischenko, Dmitry S; Naumov, Vladimir A; Bogomazova, Alexandra N; Vassina, Ekaterina M; Alekseev, Dmitry G; Lagarkova, Maria A; Kiselev, Sergey L

    2016-01-01

    The pluripotency of newly developed human induced pluripotent stem cells (iPSCs) is usually characterized by physiological parameters; i.e., by their ability to maintain the undifferentiated state and to differentiate into derivatives of the 3 germ layers. Nevertheless, a molecular comparison of physiologically normal iPSCs to the "gold standard" of pluripotency, embryonic stem cells (ESCs), often reveals a set of genes with different expression and/or methylation patterns in iPSCs and ESCs. To evaluate the contribution of the reprogramming process, parental cell type, and fortuity in the signature of human iPSCs, we developed a complete isogenic reprogramming system. We performed a genome-wide comparison of the transcriptome and the methylome of human isogenic ESCs, 3 types of ESC-derived somatic cells (fibroblasts, retinal pigment epithelium and neural cells), and 3 pairs of iPSC lines derived from these somatic cells. Our analysis revealed a high input of stochasticity in the iPSC signature that does not retain specific traces of the parental cell type and reprogramming process. We showed that 5 iPSC clones are sufficient to find with 95% confidence at least one iPSC clone indistinguishable from their hypothetical isogenic ESC line. Additionally, on the basis of a small set of genes that are characteristic of all iPSC lines and isogenic ESCs, we formulated an approach of "the best iPSC line" selection and confirmed it on an independent dataset.

  3. Identifying potential risk situations for humans when removing horses from groups

    DEFF Research Database (Denmark)

    Hartmann, Elke; Søndergaard, Eva; Keeling, Linda J.

    2012-01-01

    Removing a horse from its social group may be considered risky, both for the handler and the horse, because other horses can interfere in the catching process. The main aim of this study was to identify where and when these risk situations occur while removing a horse from its group. A potential...

  4. Identifying serotonergic mechanisms underlying the corticolimbic response to threat in humans

    DEFF Research Database (Denmark)

    Fisher, Patrick M; Hariri, Ahmad R

    2013-01-01

    . Integrating these methodological approaches offers novel opportunities to identify mechanisms through which serotonin signalling contributes to differences in brain function and behaviour, which in turn can illuminate factors that confer risk for illness and inform the development of more effective treatment...

  5. An Internet-Accessible DNA Sequence Database for Identifying Fusaria from Human and Animal Infections

    Science.gov (United States)

    Because less than one-third of clinically relevant fusaria can be accurately identified to species level using phenotypic data (i.e., morphological species recognition), we constructed a three-locus DNA sequence database to facilitate molecular identification of the 69 Fusarium species associated wi...

  6. Generalising human demonstration data by identifying affordance symmetries in object interaction trajectories

    CSIR Research Space (South Africa)

    Claassens, J

    2011-09-01

    Full Text Available presents a formal description of a set of these symmetries, which are termed affordance symmetries, and a method to identify them in multiple demonstration recordings. The approach is robust to arbitrary motion before and after the symmetry artifact...

  7. Identifying cytotoxic T cell epitopes from genomic and proteomic information: "The human MHC project."

    DEFF Research Database (Denmark)

    Lauemøller, S L; Kesmir, C; Corbet, S L

    2000-01-01

    discrimination, even at the peptide level. It is not surprising that peptides are key targets of the immune system. It follows that proteomes can be translated into immunogens once it is known how the immune system generates and handles peptides. Recent advances have identified many of the basic principles...

  8. Identifying novel genes for atherosclerosis through mouse-human comparative genetics

    NARCIS (Netherlands)

    Wang, XS; Ishimori, N; Korstanje, R; Rollins, J; Paigen, B

    Susceptibility to atherosclerosis is determined by both environmental and genetic factors. Its genetic determinants have been studied by use of quantitative- trait - locus ( QTL) analysis. So far, 21 atherosclerosis QTLs have been identified in the mouse: 7 in a high- fat - diet model only, 9 in a

  9. Silicon photonics: some remaining challenges

    Science.gov (United States)

    Reed, G. T.; Topley, R.; Khokhar, A. Z.; Thompson, D. J.; Stanković, S.; Reynolds, S.; Chen, X.; Soper, N.; Mitchell, C. J.; Hu, Y.; Shen, L.; Martinez-Jimenez, G.; Healy, N.; Mailis, S.; Peacock, A. C.; Nedeljkovic, M.; Gardes, F. Y.; Soler Penades, J.; Alonso-Ramos, C.; Ortega-Monux, A.; Wanguemert-Perez, G.; Molina-Fernandez, I.; Cheben, P.; Mashanovich, G. Z.

    2016-03-01

    This paper discusses some of the remaining challenges for silicon photonics, and how we at Southampton University have approached some of them. Despite phenomenal advances in the field of Silicon Photonics, there are a number of areas that still require development. For short to medium reach applications, there is a need to improve the power consumption of photonic circuits such that inter-chip, and perhaps intra-chip applications are viable. This means that yet smaller devices are required as well as thermally stable devices, and multiple wavelength channels. In turn this demands smaller, more efficient modulators, athermal circuits, and improved wavelength division multiplexers. The debate continues as to whether on-chip lasers are necessary for all applications, but an efficient low cost laser would benefit many applications. Multi-layer photonics offers the possibility of increasing the complexity and effectiveness of a given area of chip real estate, but it is a demanding challenge. Low cost packaging (in particular, passive alignment of fibre to waveguide), and effective wafer scale testing strategies, are also essential for mass market applications. Whilst solutions to these challenges would enhance most applications, a derivative technology is emerging, that of Mid Infra-Red (MIR) silicon photonics. This field will build on existing developments, but will require key enhancements to facilitate functionality at longer wavelengths. In common with mainstream silicon photonics, significant developments have been made, but there is still much left to do. Here we summarise some of our recent work towards wafer scale testing, passive alignment, multiplexing, and MIR silicon photonics technology.

  10. Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

    International Nuclear Information System (INIS)

    Klopfleisch, Robert; Lenze, Dido; Hummel, Michael; Gruber, Achim D

    2010-01-01

    Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a

  11. Structure modeling of all identified G protein-coupled receptors in the human genome.

    Science.gov (United States)

    Zhang, Yang; Devries, Mark E; Skolnick, Jeffrey

    2006-02-01

    G protein-coupled receptors (GPCRs), encoded by about 5% of human genes, comprise the largest family of integral membrane proteins and act as cell surface receptors responsible for the transduction of endogenous signal into a cellular response. Although tertiary structural information is crucial for function annotation and drug design, there are few experimentally determined GPCR structures. To address this issue, we employ the recently developed threading assembly refinement (TASSER) method to generate structure predictions for all 907 putative GPCRs in the human genome. Unlike traditional homology modeling approaches, TASSER modeling does not require solved homologous template structures; moreover, it often refines the structures closer to native. These features are essential for the comprehensive modeling of all human GPCRs when close homologous templates are absent. Based on a benchmarked confidence score, approximately 820 predicted models should have the correct folds. The majority of GPCR models share the characteristic seven-transmembrane helix topology, but 45 ORFs are predicted to have different structures. This is due to GPCR fragments that are predominantly from extracellular or intracellular domains as well as database annotation errors. Our preliminary validation includes the automated modeling of bovine rhodopsin, the only solved GPCR in the Protein Data Bank. With homologous templates excluded, the final model built by TASSER has a global C(alpha) root-mean-squared deviation from native of 4.6 angstroms, with a root-mean-squared deviation in the transmembrane helix region of 2.1 angstroms. Models of several representative GPCRs are compared with mutagenesis and affinity labeling data, and consistent agreement is demonstrated. Structure clustering of the predicted models shows that GPCRs with similar structures tend to belong to a similar functional class even when their sequences are diverse. These results demonstrate the usefulness and robustness

  12. Structure modeling of all identified G protein-coupled receptors in the human genome.

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    2006-02-01

    Full Text Available G protein-coupled receptors (GPCRs, encoded by about 5% of human genes, comprise the largest family of integral membrane proteins and act as cell surface receptors responsible for the transduction of endogenous signal into a cellular response. Although tertiary structural information is crucial for function annotation and drug design, there are few experimentally determined GPCR structures. To address this issue, we employ the recently developed threading assembly refinement (TASSER method to generate structure predictions for all 907 putative GPCRs in the human genome. Unlike traditional homology modeling approaches, TASSER modeling does not require solved homologous template structures; moreover, it often refines the structures closer to native. These features are essential for the comprehensive modeling of all human GPCRs when close homologous templates are absent. Based on a benchmarked confidence score, approximately 820 predicted models should have the correct folds. The majority of GPCR models share the characteristic seven-transmembrane helix topology, but 45 ORFs are predicted to have different structures. This is due to GPCR fragments that are predominantly from extracellular or intracellular domains as well as database annotation errors. Our preliminary validation includes the automated modeling of bovine rhodopsin, the only solved GPCR in the Protein Data Bank. With homologous templates excluded, the final model built by TASSER has a global C(alpha root-mean-squared deviation from native of 4.6 angstroms, with a root-mean-squared deviation in the transmembrane helix region of 2.1 angstroms. Models of several representative GPCRs are compared with mutagenesis and affinity labeling data, and consistent agreement is demonstrated. Structure clustering of the predicted models shows that GPCRs with similar structures tend to belong to a similar functional class even when their sequences are diverse. These results demonstrate the usefulness

  13. Identifying keystone species in the human gut microbiome from metagenomic timeseries using sparse linear regression.

    Directory of Open Access Journals (Sweden)

    Charles K Fisher

    Full Text Available Human associated microbial communities exert tremendous influence over human health and disease. With modern metagenomic sequencing methods it is now possible to follow the relative abundance of microbes in a community over time. These microbial communities exhibit rich ecological dynamics and an important goal of microbial ecology is to infer the ecological interactions between species directly from sequence data. Any algorithm for inferring ecological interactions must overcome three major obstacles: 1 a correlation between the abundances of two species does not imply that those species are interacting, 2 the sum constraint on the relative abundances obtained from metagenomic studies makes it difficult to infer the parameters in timeseries models, and 3 errors due to experimental uncertainty, or mis-assignment of sequencing reads into operational taxonomic units, bias inferences of species interactions due to a statistical problem called "errors-in-variables". Here we introduce an approach, Learning Interactions from MIcrobial Time Series (LIMITS, that overcomes these obstacles. LIMITS uses sparse linear regression with boostrap aggregation to infer a discrete-time Lotka-Volterra model for microbial dynamics. We tested LIMITS on synthetic data and showed that it could reliably infer the topology of the inter-species ecological interactions. We then used LIMITS to characterize the species interactions in the gut microbiomes of two individuals and found that the interaction networks varied significantly between individuals. Furthermore, we found that the interaction networks of the two individuals are dominated by distinct "keystone species", Bacteroides fragilis and Bacteroided stercosis, that have a disproportionate influence on the structure of the gut microbiome even though they are only found in moderate abundance. Based on our results, we hypothesize that the abundances of certain keystone species may be responsible for individuality in

  14. A biotin enrichment strategy identifies novel carbonylated amino acids in proteins from human plasma

    DEFF Research Database (Denmark)

    Havelund, Jesper F; Wojdyla, Katarzyna; Davies, Michael J

    2017-01-01

    Protein carbonylation is an irreversible protein oxidation correlated with oxidative stress, various diseases and ageing. Here we describe a peptide-centric approach for identification and characterisation of up to 14 different types of carbonylated amino acids in proteins. The modified residues...... in vitro metal ion-catalysed oxidation. Furthermore, we assigned 133 carbonylated sites in 36 proteins in native human plasma protein samples. The optimised workflow enabled detection of 10 hitherto undetected types of carbonylated amino acids in proteins: aldehyde and ketone modifications of leucine...

  15. Identifying anti-growth factors for human cancer cell lines through genome-scale metabolic modeling

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Asplund, Anna

    2015-01-01

    Human cancer cell lines are used as important model systems to study molecular mechanisms associated with tumor growth, hereunder how genomic and biological heterogeneity found in primary tumors affect cellular phenotypes. We reconstructed Genome scale metabolic models (GEMs) for eleven cell lines...... based on RNA-Seq data and validated the functionality of these models with data from metabolite profiling. We used cell line-specific GEMs to analyze the differences in the metabolism of cancer cell lines, and to explore the heterogeneous expression of the metabolic subsystems. Furthermore, we predicted...... for inhibition of cell growth may provide leads for the development of efficient cancer treatment strategies....

  16. Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.

    Science.gov (United States)

    Zanotto-Filho, Alfeu; Dashnamoorthy, Ravi; Loranc, Eva; de Souza, Luis H T; Moreira, José C F; Suresh, Uthra; Chen, Yidong; Bishop, Alexander J R

    2016-01-01

    Alkylating agents are a key component of cancer chemotherapy. Several cellular mechanisms are known to be important for its survival, particularly DNA repair and xenobiotic detoxification, yet genomic screens indicate that additional cellular components may be involved. Elucidating these components has value in either identifying key processes that can be modulated to improve chemotherapeutic efficacy or may be altered in some cancers to confer chemoresistance. We therefore set out to reevaluate our prior Drosophila RNAi screening data by comparison to gene expression arrays in order to determine if we could identify any novel processes in alkylation damage survival. We noted a consistent conservation of alkylation survival pathways across platforms and species when the analysis was conducted on a pathway/process level rather than at an individual gene level. Better results were obtained when combining gene lists from two datasets (RNAi screen plus microarray) prior to analysis. In addition to previously identified DNA damage responses (p53 signaling and Nucleotide Excision Repair), DNA-mRNA-protein metabolism (transcription/translation) and proteasome machinery, we also noted a highly conserved cross-species requirement for NRF2, glutathione (GSH)-mediated drug detoxification and Endoplasmic Reticulum stress (ER stress)/Unfolded Protein Responses (UPR) in cells exposed to alkylation. The requirement for GSH, NRF2 and UPR in alkylation survival was validated by metabolomics, protein studies and functional cell assays. From this we conclude that RNAi/gene expression fusion is a valid strategy to rapidly identify key processes that may be extendable to other contexts beyond damage survival.

  17. Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.

    Directory of Open Access Journals (Sweden)

    Alfeu Zanotto-Filho

    Full Text Available Alkylating agents are a key component of cancer chemotherapy. Several cellular mechanisms are known to be important for its survival, particularly DNA repair and xenobiotic detoxification, yet genomic screens indicate that additional cellular components may be involved. Elucidating these components has value in either identifying key processes that can be modulated to improve chemotherapeutic efficacy or may be altered in some cancers to confer chemoresistance. We therefore set out to reevaluate our prior Drosophila RNAi screening data by comparison to gene expression arrays in order to determine if we could identify any novel processes in alkylation damage survival. We noted a consistent conservation of alkylation survival pathways across platforms and species when the analysis was conducted on a pathway/process level rather than at an individual gene level. Better results were obtained when combining gene lists from two datasets (RNAi screen plus microarray prior to analysis. In addition to previously identified DNA damage responses (p53 signaling and Nucleotide Excision Repair, DNA-mRNA-protein metabolism (transcription/translation and proteasome machinery, we also noted a highly conserved cross-species requirement for NRF2, glutathione (GSH-mediated drug detoxification and Endoplasmic Reticulum stress (ER stress/Unfolded Protein Responses (UPR in cells exposed to alkylation. The requirement for GSH, NRF2 and UPR in alkylation survival was validated by metabolomics, protein studies and functional cell assays. From this we conclude that RNAi/gene expression fusion is a valid strategy to rapidly identify key processes that may be extendable to other contexts beyond damage survival.

  18. Identifying candidate agents for lung adenocarcinoma by walking the human interactome

    Directory of Open Access Journals (Sweden)

    Sun Y

    2016-09-01

    Full Text Available Yajiao Sun,1 Ranran Zhang,2 Zhe Jiang,1 Rongyao Xia,1 Jingwen Zhang,1 Jing Liu,1 Fuhui Chen1 1Department of Respiratory, The Second Affiliated Hospital of Harbin Medical University, 2Department of Respiratory, Harbin First Hospital, Harbin, People’s Republic of China Abstract: Despite recent advances in therapeutic strategies for lung cancer, mortality is still increasing. Therefore, there is an urgent need to identify effective novel drugs. In the present study, we implement drug repositioning for lung adenocarcinoma (LUAD by a bioinformatics method followed by experimental validation. We first identified differentially expressed genes between LUAD tissues and nontumor tissues from RNA sequencing data obtained from The Cancer Genome Atlas database. Then, candidate small molecular drugs were ranked according to the effect of their targets on differentially expressed genes of LUAD by a random walk with restart algorithm in protein–protein interaction networks. Our method identified some potentially novel agents for LUAD besides those that had been previously reported (eg, hesperidin. Finally, we experimentally verified that atracurium, one of the potential agents, could induce A549 cells death in non-small-cell lung cancer-derived A549 cells by an MTT assay, acridine orange and ethidium bromide staining, and electron microscopy. Furthermore, Western blot assays demonstrated that atracurium upregulated the proapoptotic Bad and Bax proteins, downregulated the antiapoptotic p-Bad and Bcl-2 proteins, and enhanced caspase-3 activity. It could also reduce the expression of p53 and p21Cip1/Waf1 in A549 cells. In brief, the candidate agents identified by our approach may provide greater insights into improving the therapeutic status of LUAD. Keywords: lung adenocarcinoma, drug repositioning, bioinformatics, protein–protein interaction network, atracurium

  19. Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods

    DEFF Research Database (Denmark)

    Jakobsen, Lis; Vanselow, Katja; Skogs, Marie

    2011-01-01

    by identifying a novel set of five proteins preferentially associated with mother or daughter centrioles, comprising genes implicated in cell polarity. Pulsed labelling demonstrates a remarkable variation in the stability of centrosomal protein complexes. These spatiotemporal proteomics data provide leads......Centrosomes in animal cells are dynamic organelles with a proteinaceous matrix of pericentriolar material assembled around a pair of centrioles. They organize the microtubule cytoskeleton and the mitotic spindle apparatus. Mature centrioles are essential for biogenesis of primary cilia that mediate...

  20. Gene expression profile identifies potential biomarkers for human intervertebral disc degeneration.

    Science.gov (United States)

    Guo, Wei; Zhang, Bin; Li, Yan; Duan, Hui-Quan; Sun, Chao; Xu, Yun-Qiang; Feng, Shi-Qing

    2017-12-01

    The present study aimed to reveal the potential genes associated with the pathogenesis of intervertebral disc degeneration (IDD) by analyzing microarray data using bioinformatics. Gene expression profiles of two regions of the intervertebral disc were compared between patients with IDD and controls. GSE70362 containing two groups of gene expression profiles, 16 nucleus pulposus (NP) samples from patients with IDD and 8 from controls, and 16 annulus fibrosus (AF) samples from patients with IDD and 8 from controls, was downloaded from the Gene Expression Omnibus database. A total of 93 and 114 differentially expressed genes (DEGs) were identified in NP and AF samples, respectively, using a limma software package for the R programming environment. Gene Ontology (GO) function enrichment analysis was performed to identify the associated biological functions of DEGs in IDD, which indicated that the DEGs may be involved in various processes, including cell adhesion, biological adhesion and extracellular matrix organization. Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated that the identified DEGs were potentially involved in focal adhesion and the p53 signaling pathway. Further analysis revealed that there were 35 common DEGs observed between the two regions (NP and AF), which may be further regulated by 6 clusters of microRNAs (miRNAs) retrieved with WebGestalt. The genes in the DEG‑miRNA regulatory network were annotated using GO function and KEGG pathway enrichment analysis, among which extracellular matrix organization was the most significant disrupted biological process and focal adhesion was the most significant dysregulated pathway. In addition, the result of protein‑protein interaction network modules demonstrated the involvement of inflammatory cytokine interferon signaling in IDD. These findings may not only advance the understanding of the pathogenesis of IDD, but also identify novel potential

  1. High-density polymer microarrays: identifying synthetic polymers that control human embryonic stem cell growth.

    Science.gov (United States)

    Hansen, Anne; Mjoseng, Heidi K; Zhang, Rong; Kalloudis, Michail; Koutsos, Vasileios; de Sousa, Paul A; Bradley, Mark

    2014-06-01

    The fabrication of high-density polymer microarray is described, allowing the simultaneous and efficient evaluation of more than 7000 different polymers in a single-cellular-based screen. These high-density polymer arrays are applied in the search for synthetic substrates for hESCs culture. Up-scaling of the identified hit polymers enables long-term cellular cultivation and promoted successful stem-cell maintenance. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Therapeutic molecules for multiple human diseases identified from pigeon pea (Cajanus cajan L. Millsp. through GC–MS and molecular docking

    Directory of Open Access Journals (Sweden)

    Deepu Mathew

    2017-12-01

    Full Text Available Molecular mechanism behind the therapeutic potential of pigeon pea over the human diseases such as rheumatoid arthritis, breast cancer, type II diabetes, malaria, measles and sickle cell disease were revealed through docking of GC–MS identified phyto-compound ligands with candidate disease proteins. Of the 242 ligands, three dimensional structures of 47 compounds had to be drawn using ChemSketch and the remaining structures were retrieved from PubChem and docked with the active sites of candidate proteins. The molecules identified through docking were further subjected to ADMET analysis and promising drug candidates were identified for each disease. This paper presents a precise account of the chemoprofile of pigeon pea leaves, stems and seeds, interaction of these molecules with target proteins and suggests 26 highly potential molecules which are drug candidates for multiple human diseases. Pigeon pea seeds are especially proven as invaluable source for therapeutic molecules. Keywords: Breast cancer, Drug discovery, Herbal medicine, In silico, Malaria, Measles, Phyto-compounds, Rheumatoid arthritis, Sickle cell disease, Type II diabetes

  3. Domain-restricted mutation analysis to identify novel driver events in human cancer

    Directory of Open Access Journals (Sweden)

    Sanket Desai

    2017-10-01

    Full Text Available Analysis of mutational spectra across various cancer types has given valuable insights into tumorigenesis. Different approaches have been used to identify novel drivers from the set of somatic mutations, including the methods which use sequence conservation, geometric localization and pathway information. Recent computational methods suggest use of protein domain information for analysis and understanding of the functional consequence of non-synonymous mutations. Similarly, evidence suggests recurrence at specific position in proteins is robust indicators of its functional impact. Building on this, we performed a systematic analysis of TCGA exome derived somatic mutations across 6089 PFAM domains and significantly mutated domains were identified using randomization approach. Multiple alignment of individual domain allowed us to prioritize for conserved residues mutated at analogous positions across different proteins in a statistically disciplined manner. In addition to the known frequently mutated genes, this analysis independently identifies low frequency Meprin and TRAF-Homology (MATH domain in Speckle Type BTB/POZ (SPOP protein, in prostate adenocarcinoma. Results from this analysis will help generate hypotheses about the downstream molecular mechanism resulting in cancer phenotypes.

  4. Identifying indicators of illegal behaviour: carnivore killing in human-managed landscapes.

    Science.gov (United States)

    St John, Freya A V; Keane, Aidan M; Edwards-Jones, Gareth; Jones, Lauren; Yarnell, Richard W; Jones, Julia P G

    2012-02-22

    Managing natural resources often depends on influencing people's behaviour, however effectively targeting interventions to discourage environmentally harmful behaviours is challenging because those involved may be unwilling to identify themselves. Non-sensitive indicators of sensitive behaviours are therefore needed. Previous studies have investigated people's attitudes, assuming attitudes reflect behaviour. There has also been interest in using people's estimates of the proportion of their peers involved in sensitive behaviours to identify those involved, since people tend to assume that others behave like themselves. However, there has been little attempt to test the potential of such indicators. We use the randomized response technique (RRT), designed for investigating sensitive behaviours, to estimate the proportion of farmers in north-eastern South Africa killing carnivores, and use a modified logistic regression model to explore relationships between our best estimates of true behaviour (from RRT) and our proposed non-sensitive indicators (including farmers' attitudes, and estimates of peer-behaviour). Farmers' attitudes towards carnivores, question sensitivity and estimates of peers' behaviour, predict the likelihood of farmers killing carnivores. Attitude and estimates of peer-behaviour are useful indicators of involvement in illicit behaviours and may be used to identify groups of people to engage in interventions aimed at changing behaviour.

  5. Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data.

    Science.gov (United States)

    Ren, Zhonglu; Wang, Wenhui; Li, Jinming

    2016-02-01

    Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristics of each subtype. Clustering analysis and discriminant analysis were utilized to discover the subtypes in two different molecular levels on 153 colon cancer samples from The Cancer Genome Atlas (TCGA) Data Portal. At gene expression level, we identified two major subtypes, ECL1 (expression cluster 1) and ECL2 (expression cluster 2) and a list of signature genes. Due to the heterogeneity of colon cancer, the subtype ECL1 can be further subdivided into three nested subclasses, and HOTAIR were found upregulated in subclass 2. At DNA methylation level, we uncovered three major subtypes, MCL1 (methylation cluster 1), MCL2 (methylation cluster 2) and MCL3 (methylation cluster 3). We found only three subtypes of CpG island methylator phenotype (CIMP) in colon cancer instead of the four subtypes in the previous reports, and we found no sufficient evidence to subdivide MCL3 into two distinct subgroups.

  6. Cross-comparison of the genome sequences from human, chimpanzee, Neanderthal and a Denisovan hominin identifies novel potentially compensated mutations

    Directory of Open Access Journals (Sweden)

    Zhang Guojie

    2011-07-01

    Full Text Available Abstract The recent publication of the draft genome sequences of the Neanderthal and a ~50,000-year-old archaic hominin from Denisova Cave in southern Siberia has ushered in a new age in molecular archaeology. We previously cross-compared the human, chimpanzee and Neanderthal genome sequences with respect to a set of disease-causing/disease-associated missense and regulatory mutations (Human Gene Mutation Database and succeeded in identifying genetic variants which, although apparently pathogenic in humans, may represent a 'compensated' wild-type state in at least one of the other two species. Here, in an attempt to identify further 'potentially compensated mutations' (PCMs of interest, we have compared our dataset of disease-causing/disease-associated mutations with their corresponding nucleotide positions in the Denisovan hominin, Neanderthal and chimpanzee genomes. Of the 15 human putatively disease-causing mutations that were found to be compensated in chimpanzee, Denisovan or Neanderthal, only a solitary F5 variant (Val1736Met was specific to the Denisovan. In humans, this missense mutation is associated with activated protein C resistance and an increased risk of thromboembolism and recurrent miscarriage. It is unclear at this juncture whether this variant was indeed a PCM in the Denisovan or whether it could instead have been associated with disease in this ancient hominin.

  7. Genome-wide association study identifies candidate genes for male fertility traits in humans.

    Science.gov (United States)

    Kosova, Gülüm; Scott, Nicole M; Niederberger, Craig; Prins, Gail S; Ober, Carole

    2012-06-08

    Despite the fact that hundreds of genes are known to affect fertility in animal models, relatively little is known about genes that influence natural fertility in humans. To broadly survey genes contributing to variation in male fertility, we conducted a genome-wide association study (GWAS) of two fertility traits (family size and birth rate) in 269 married men who are members of a founder population of European descent that proscribes contraception and has large family sizes. Associations between ∼250,000 autosomal SNPs and the fertility traits were examined. A total of 41 SNPs with p ≤ 1 × 10(-4) for either trait were taken forward to a validation study of 123 ethnically diverse men from Chicago who had previously undergone semen analyses. Nine (22%) of the SNPs associated with reduced fertility in the GWAS were also associated with one or more of the ten measures of reduced sperm quantity and/or function, yielding 27 associations with p values LRRC32, which encodes a latent transforming growth factor β (TGF-β) receptor on regulatory T cells. We suggest that mutations in these genes that are more severe may account for some of the unexplained infertility (or subfertility) in the general population. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. Human-Chromatin-Related Protein Interactions Identify a Demethylase Complex Required for Chromosome Segregation

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    Edyta Marcon

    2014-07-01

    Full Text Available Chromatin regulation is driven by multicomponent protein complexes, which form functional modules. Deciphering the components of these modules and their interactions is central to understanding the molecular pathways these proteins are regulating, their functions, and their relation to both normal development and disease. We describe the use of affinity purifications of tagged human proteins coupled with mass spectrometry to generate a protein-protein interaction map encompassing known and predicted chromatin-related proteins. On the basis of 1,394 successful purifications of 293 proteins, we report a high-confidence (85% precision network involving 11,464 protein-protein interactions among 1,738 different human proteins, grouped into 164 often overlapping protein complexes with a particular focus on the family of JmjC-containing lysine demethylases, their partners, and their roles in chromatin remodeling. We show that RCCD1 is a partner of histone H3K36 demethylase KDM8 and demonstrate that both are important for cell-cycle-regulated transcriptional repression in centromeric regions and accurate mitotic division.

  9. Epistasis between dopamine regulating genes identifies a nonlinear response of the human hippocampus during memory tasks.

    Science.gov (United States)

    Bertolino, Alessandro; Di Giorgio, Annabella; Blasi, Giuseppe; Sambataro, Fabio; Caforio, Grazia; Sinibaldi, Lorenzo; Latorre, Valeria; Rampino, Antonio; Taurisano, Paolo; Fazio, Leonardo; Romano, Raffaella; Douzgou, Sofia; Popolizio, Teresa; Kolachana, Bhaskar; Nardini, Marcello; Weinberger, Daniel R; Dallapiccola, Bruno

    2008-08-01

    Dopamine modulation of neuronal activity in prefrontal cortex maps to an inverted U-curve. Dopamine is also an important factor in regulation of hippocampal mediated memory processing. Here, we investigated the effect of genetic variation of dopamine inactivation via catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) on hippocampal activity in healthy humans during different memory conditions. Using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in 82 subjects matched for a series of demographic and genetic variables, we studied the effect of the COMT valine (Val)(158)methionine (Met) and the DAT 3' variable number tandem repeat (VNTR) polymorphisms on function of the hippocampus during encoding of recognition memory and during working memory. Our results consistently demonstrated a double dissociation so that DAT 9-repeat carrier alleles modulated activity in the hippocampus in the exact opposite direction of DAT 10/10-repeat alleles based on COMT Val(158)Met genotype during different memory conditions. Similar results were evident in ventrolateral and dorsolateral prefrontal cortex. These findings suggest that genetically determined dopamine signaling during memory processing maps to a nonlinear relationship also in the hippocampus. Our data also demonstrate in human brain epistasis of two genes implicated in dopamine signaling on brain activity during different memory conditions.

  10. A Western diet ecological module identified from the 'humanized' mouse microbiota predicts diet in adults and formula feeding in children.

    Science.gov (United States)

    Siddharth, Jay; Holway, Nicholas; Parkinson, Scott J

    2013-01-01

    The interplay between diet and the microbiota has been implicated in the growing frequency of chronic diseases associated with the Western lifestyle. However, the complexity and variability of microbial ecology in humans and preclinical models has hampered identification of the molecular mechanisms underlying the association of the microbiota in this context. We sought to address two key questions. Can the microbial ecology of preclinical models predict human populations? And can we identify underlying principles that surpass the plasticity of microbial ecology in humans? To do this, we focused our study on diet; perhaps the most influential factor determining the composition of the gut microbiota. Beginning with a study in 'humanized' mice we identified an interactive module of 9 genera allied with Western diet intake. This module was applied to a controlled dietary study in humans. The abundance of the Western ecological module correctly predicted the dietary intake of 19/21 top and 21/21 of the bottom quartile samples inclusive of all 5 Western and 'low-fat' diet subjects, respectively. In 98 volunteers the abundance of the Western module correlated appropriately with dietary intake of saturated fatty acids, fat-soluble vitamins and fiber. Furthermore, it correlated with the geographical location and dietary habits of healthy adults from the Western, developing and third world. The module was also coupled to dietary intake in children (and piglets) correlating with formula (vs breast) feeding and associated with a precipitous development of the ecological module in young children. Our study provides a conceptual platform to translate microbial ecology from preclinical models to humans and identifies an ecological network module underlying the association of the gut microbiota with Western dietary habits.

  11. A Western diet ecological module identified from the 'humanized' mouse microbiota predicts diet in adults and formula feeding in children.

    Directory of Open Access Journals (Sweden)

    Jay Siddharth

    Full Text Available The interplay between diet and the microbiota has been implicated in the growing frequency of chronic diseases associated with the Western lifestyle. However, the complexity and variability of microbial ecology in humans and preclinical models has hampered identification of the molecular mechanisms underlying the association of the microbiota in this context. We sought to address two key questions. Can the microbial ecology of preclinical models predict human populations? And can we identify underlying principles that surpass the plasticity of microbial ecology in humans? To do this, we focused our study on diet; perhaps the most influential factor determining the composition of the gut microbiota. Beginning with a study in 'humanized' mice we identified an interactive module of 9 genera allied with Western diet intake. This module was applied to a controlled dietary study in humans. The abundance of the Western ecological module correctly predicted the dietary intake of 19/21 top and 21/21 of the bottom quartile samples inclusive of all 5 Western and 'low-fat' diet subjects, respectively. In 98 volunteers the abundance of the Western module correlated appropriately with dietary intake of saturated fatty acids, fat-soluble vitamins and fiber. Furthermore, it correlated with the geographical location and dietary habits of healthy adults from the Western, developing and third world. The module was also coupled to dietary intake in children (and piglets correlating with formula (vs breast feeding and associated with a precipitous development of the ecological module in young children. Our study provides a conceptual platform to translate microbial ecology from preclinical models to humans and identifies an ecological network module underlying the association of the gut microbiota with Western dietary habits.

  12. Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity.

    Science.gov (United States)

    Montoliu, Ivan; Scherer, Max; Beguelin, Fiona; DaSilva, Laeticia; Mari, Daniela; Salvioli, Stefano; Martin, Francois-Pierre J; Capri, Miriam; Bucci, Laura; Ostan, Rita; Garagnani, Paolo; Monti, Daniela; Biagi, Elena; Brigidi, Patrizia; Kussmann, Martin; Rezzi, Serge; Franceschi, Claudio; Collino, Sebastiano

    2014-01-01

    As centenarians well represent the model of healthy aging, there are many important implications in revealing the underlying molecular mechanisms behind such successful aging. By combining NMR metabonomics and shot-gun lipidomics in serum we analyzed metabolome and lipidome composition of a group of centenarians with respect to elderly individuals. Specifically, NMR metabonomics profiling of serum revealed that centenarians are characterized by a metabolic phenotype distinct from that of elderly subjects, in particular regarding amino acids and lipid species. Shot- gun lipidomics approach displays unique changes in lipids biosynthesis in centenarians, with 41 differently abundant lipid species with respect to elderly subjects. These findings reveal phospho/sphingolipids as putative markers and biological modulators of healthy aging, in humans. Considering the particular actions of these metabolites, these data are suggestive of a better counteractive antioxidant capacity and a well-developed membrane lipid remodelling process in the healthy aging phenotype.

  13. Preservation Analysis of Macrophage Gene Coexpression Between Human and Mouse Identifies PARK2 as a Genetically Controlled Master Regulator of Oxidative Phosphorylation in Humans

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    Veronica Codoni

    2016-10-01

    Full Text Available Macrophages are key players involved in numerous pathophysiological pathways and an in-depth characterization of their gene regulatory networks can help in better understanding how their dysfunction may impact on human diseases. We here conducted a cross-species network analysis of macrophage gene expression data between human and mouse to identify conserved networks across both species, and assessed whether such networks could reveal new disease-associated regulatory mechanisms. From a sample of 684 individuals processed for genome-wide macrophage gene expression profiling, we identified 27 groups of coexpressed genes (modules. Six modules were found preserved (P < 10−4 in macrophages from 86 mice of the Hybrid Mouse Diversity Panel. One of these modules was significantly [false discovery rate (FDR = 8.9 × 10−11] enriched for genes belonging to the oxidative phosphorylation (OXPHOS pathway. This pathway was also found significantly (FDR < 10−4 enriched in susceptibility genes for Alzheimer, Parkinson, and Huntington diseases. We further conducted an expression quantitative trait loci analysis to identify SNP that could regulate macrophage OXPHOS gene expression in humans. This analysis identified the PARK2 rs192804963 as a trans-acting variant influencing (minimal P-value = 4.3 × 10−8 the expression of most OXPHOS genes in humans. Further experimental work demonstrated that PARK2 knockdown expression was associated with increased OXPHOS gene expression in THP1 human macrophages. This work provided strong new evidence that PARK2 participates to the regulatory networks associated with oxidative phosphorylation and suggested that PARK2 genetic variations could act as a trans regulator of OXPHOS gene macrophage expression in humans.

  14. Secondary uses and the governance of de-identified data: Lessons from the human genome diversity panel

    Directory of Open Access Journals (Sweden)

    Lee Sandra S-J

    2011-09-01

    Full Text Available Abstract Background Recent changes to regulatory guidance in the US and Europe have complicated oversight of secondary research by rendering most uses of de-identified data exempt from human subjects oversight. To identify the implications of such guidelines for harms to participants and communities, this paper explores the secondary uses of one de-identified DNA sample collection with limited oversight: the Human Genome Diversity Project (HGDP-Centre d'Etude du Polymorphisme Humain, Fondation Jean Dausset (CEPH Human Genome Diversity Panel. Methods Using a combination of keyword and cited reference search, we identified English-language scientific articles published between 2002 and 2009 that reported analysis of HGDP Diversity Panel samples and/or data. We then reviewed each article to identify the specific research use to which the samples and/or data was applied. Secondary uses were categorized according to the type and kind of research supported by the collection. Results A wide variety of secondary uses were identified from 148 peer-reviewed articles. While the vast majority of these uses were consistent with the original intent of the collection, a minority of published reports described research whose primary findings could be regarded as controversial, objectionable, or potentially stigmatizing in their interpretation. Conclusions We conclude that potential risks to participants and communities cannot be wholly eliminated by anonymization of individual data and suggest that explicit review of proposed secondary uses, by a Data Access Committee or similar internal oversight body with suitable stakeholder representation, should be a required component of the trustworthy governance of any repository of data or specimens.

  15. Perturbation-expression analysis identifies RUNX1 as a regulator of human mammary stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Ethan S Sokol

    2015-04-01

    Full Text Available The search for genes that regulate stem cell self-renewal and differentiation has been hindered by a paucity of markers that uniquely label stem cells and early progenitors. To circumvent this difficulty we have developed a method that identifies cell-state regulators without requiring any markers of differentiation, termed Perturbation-Expression Analysis of Cell States (PEACS. We have applied this marker-free approach to screen for transcription factors that regulate mammary stem cell differentiation in a 3D model of tissue morphogenesis and identified RUNX1 as a stem cell regulator. Inhibition of RUNX1 expanded bipotent stem cells and blocked their differentiation into ductal and lobular tissue rudiments. Reactivation of RUNX1 allowed exit from the bipotent state and subsequent differentiation and mammary morphogenesis. Collectively, our findings show that RUNX1 is required for mammary stem cells to exit a bipotent state, and provide a new method for discovering cell-state regulators when markers are not available.

  16. DNA typing of ancient parasite eggs from environmental samples identifies human and animal worm infections in Viking-age settlement.

    Science.gov (United States)

    Søe, Martin Jensen; Nejsum, Peter; Fredensborg, Brian Lund; Kapel, Christian Moliin Outzen

    2015-02-01

    Ancient parasite eggs were recovered from environmental samples collected at a Viking-age settlement in Viborg, Denmark, dated 1018-1030 A.D. Morphological examination identified Ascaris sp., Trichuris sp., and Fasciola sp. eggs, but size and shape did not allow species identification. By carefully selecting genetic markers, PCR amplification and sequencing of ancient DNA (aDNA) isolates resulted in identification of: the human whipworm, Trichuris trichiura , using SSUrRNA sequence homology; Ascaris sp. with 100% homology to cox1 haplotype 07; and Fasciola hepatica using ITS1 sequence homology. The identification of T. trichiura eggs indicates that human fecal material is present and, hence, that the Ascaris sp. haplotype 07 was most likely a human variant in Viking-age Denmark. The location of the F. hepatica finding suggests that sheep or cattle are the most likely hosts. Further, we sequenced the Ascaris sp. 18S rRNA gene in recent isolates from humans and pigs of global distribution and show that this is not a suited marker for species-specific identification. Finally, we discuss ancient parasitism in Denmark and the implementation of aDNA analysis methods in paleoparasitological studies. We argue that when employing species-specific identification, soil samples offer excellent opportunities for studies of human parasite infections and of human and animal interactions of the past.

  17. Recombinant yeast screen for new inhibitors of human acetyl-CoA carboxylase 2 identifies potential drugs to treat obesity

    Science.gov (United States)

    Marjanovic, Jasmina; Chalupska, Dominika; Patenode, Caroline; Coster, Adam; Arnold, Evan; Ye, Alice; Anesi, George; Lu, Ying; Okun, Ilya; Tkachenko, Sergey; Haselkorn, Robert; Gornicki, Piotr

    2010-01-01

    Acetyl-CoA carboxylase (ACC) is a key enzyme of fatty acid metabolism with multiple isozymes often expressed in different eukaryotic cellular compartments. ACC-made malonyl-CoA serves as a precursor for fatty acids; it also regulates fatty acid oxidation and feeding behavior in animals. ACC provides an important target for new drugs to treat human diseases. We have developed an inexpensive nonradioactive high-throughput screening system to identify new ACC inhibitors. The screen uses yeast gene-replacement strains depending for growth on cloned human ACC1 and ACC2. In “proof of concept” experiments, growth of such strains was inhibited by compounds known to target human ACCs. The screen is sensitive and robust. Medium-size chemical libraries yielded new specific inhibitors of human ACC2. The target of the best of these inhibitors was confirmed with in vitro enzymatic assays. This compound is a new drug chemotype inhibiting human ACC2 with 2.8 μM IC50 and having no effect on human ACC1 at 100 μM. PMID:20439761

  18. Clinically Detectable Dental Identifiers Observed in Intra-oral Photographs and Extra-oral Radiographs, Validated for Human Identification Purposes.

    Science.gov (United States)

    Angelakopoulos, Nikolaos; Franco, Ademir; Willems, Guy; Fieuws, Steffen; Thevissen, Patrick

    2017-07-01

    Screening the prevalence and pattern of dental identifiers contributes toward the process of human identification. This research investigated the uniqueness of clinical dental identifiers in photographs and radiographs. Panoramic and lateral cephalometric radiographs and five intra-oral photographs of 1727 subjects were used. In a target set, two observers examined different subjects. In a subset, both observers examined the same subjects (source set). The distance between source and target subjects was quantified for each identifier. The percentage of subjects in the target set being at least as close as the correct subject was assessed. The number of molars (34.6%), missing teeth (42%), and displaced teeth (59.9%) were the most unique identifiers in photographs and panoramic and lateral cephalometric radiographs, respectively. The pattern of rotated teeth (14.9%) was the most unique in photographs, while displaced teeth was in panoramic (37.6%) and lateral cephalometric (54.8%) radiographs. Morphological identifiers were the most unique, highlighting their importance for human identifications. © 2016 American Academy of Forensic Sciences.

  19. High Aldehyde Dehydrogenase Activity Identifies a Subset of Human Mesenchymal Stromal Cells with Vascular Regenerative Potential.

    Science.gov (United States)

    Sherman, Stephen E; Kuljanin, Miljan; Cooper, Tyler T; Putman, David M; Lajoie, Gilles A; Hess, David A

    2017-06-01

    During culture expansion, multipotent mesenchymal stromal cells (MSCs) differentially express aldehyde dehydrogenase (ALDH), an intracellular detoxification enzyme that protects long-lived cells against oxidative stress. Thus, MSC selection based on ALDH-activity may be used to reduce heterogeneity and distinguish MSC subsets with improved regenerative potency. After expansion of human bone marrow-derived MSCs, cell progeny was purified based on low versus high ALDH-activity (ALDH hi ) by fluorescence-activated cell sorting, and each subset was compared for multipotent stromal and provascular regenerative functions. Both ALDH l ° and ALDH hi MSC subsets demonstrated similar expression of stromal cell (>95% CD73 + , CD90 + , CD105 + ) and pericyte (>95% CD146 + ) surface markers and showed multipotent differentiation into bone, cartilage, and adipose cells in vitro. Conditioned media (CDM) generated by ALDH hi MSCs demonstrated a potent proliferative and prosurvival effect on human microvascular endothelial cells (HMVECs) under serum-free conditions and augmented HMVEC tube-forming capacity in growth factor-reduced matrices. After subcutaneous transplantation within directed in vivo angiogenesis assay implants into immunodeficient mice, ALDH hi MSC or CDM produced by ALDH hi MSC significantly augmented murine vascular cell recruitment and perfused vessel infiltration compared with ALDH l ° MSC. Although both subsets demonstrated strikingly similar mRNA expression patterns, quantitative proteomic analyses performed on subset-specific CDM revealed the ALDH hi MSC subset uniquely secreted multiple proangiogenic cytokines (vascular endothelial growth factor beta, platelet derived growth factor alpha, and angiogenin) and actively produced multiple factors with chemoattractant (transforming growth factor-β, C-X-C motif chemokine ligand 1, 2, and 3 (GRO), C-C motif chemokine ligand 5 (RANTES), monocyte chemotactic protein 1 (MCP-1), interleukin [IL]-6, IL-8) and matrix

  20. Chemicals identified in human biological media: a data base. Third annual report, October 1981

    Energy Technology Data Exchange (ETDEWEB)

    Cone, M.V.; Baldauf, M.F.; Martin, F.M. (comps.)

    1981-12-01

    Data from almost 1600 of the 3800 body-burden documents collected to date have been entered in the data base as of October 1981. The emphasis on including recent literature and significant research documents has resulted in a chronological mix of articles from 1974 to the present. When body-burden articles are identified, data are extracted and entered in the data base by chemical and tissue/body fluid. Each data entry comprises a single record (or line entry) and is assigned a record number. If a particular document deals with more than one chemical and/or tissue, there will be multiple records for that document. For example, a study of 5 chemicals in each of 3 tissues has 15 different records (or 15 line entries) in the data base with 15 record numbers. Record numbers are assigned consecutively throughout the entire data base and appear in the upper left corner of the first column for each record.

  1. Polymorphic microsatellites in the human bloodfluke, Schistosoma japonicum, identified using a genomic resource

    Directory of Open Access Journals (Sweden)

    Spear Robert

    2011-02-01

    Full Text Available Abstract Re-emergence of schistosomiasis in regions of China where control programs have ceased requires development of molecular-genetic tools to track gene flow and assess genetic diversity of Schistosoma populations. We identified many microsatellite loci in the draft genome of Schistosoma japonicum using defined search criteria and selected a subset for further analysis. From an initial panel of 50 loci, 20 new microsatellites were selected for eventual optimization and application to a panel of worms from endemic areas. All but one of the selected microsatellites contain simple tri-nucleotide repeats. Moderate to high levels of polymorphism were detected. Numbers of alleles ranged from 6 to 14 and observed heterozygosity was always >0.6. The loci reported here will facilitate high resolution population-genetic studies on schistosomes in re-emergent foci.

  2. Genome scan identifies a locus affecting gamma-globin expression in human beta-cluster YAC transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Lin, S.D.; Cooper, P.; Fung, J.; Weier, H.U.G.; Rubin, E.M.

    2000-03-01

    Genetic factors affecting post-natal g-globin expression - a major modifier of the severity of both b-thalassemia and sickle cell anemia, have been difficult to study. This is especially so in mice, an organism lacking a globin gene with an expression pattern equivalent to that of human g-globin. To model the human b-cluster in mice, with the goal of screening for loci affecting human g-globin expression in vivo, we introduced a human b-globin cluster YAC transgene into the genome of FVB mice . The b-cluster contained a Greek hereditary persistence of fetal hemoglobin (HPFH) g allele resulting in postnatal expression of human g-globin in transgenic mice. The level of human g-globin for various F1 hybrids derived from crosses between the FVB transgenics and other inbred mouse strains was assessed. The g-globin level of the C3HeB/FVB transgenic mice was noted to be significantly elevated. To map genes affecting postnatal g-globin expression, a 20 centiMorgan (cM) genome scan of a C3HeB/F VB transgenics [prime] FVB backcross was performed, followed by high-resolution marker analysis of promising loci. From this analysis we mapped a locus within a 2.2 cM interval of mouse chromosome 1 at a LOD score of 4.2 that contributes 10.4% of variation in g-globin expression level. Combining transgenic modeling of the human b-globin gene cluster with quantitative trait analysis, we have identified and mapped a murine locus that impacts on human g-globin expression in vivo.

  3. Integration of ATAC-seq and RNA-seq identifies human alpha cell and beta cell signature genes

    Directory of Open Access Journals (Sweden)

    Amanda M. Ackermann

    2016-03-01

    Conclusions: We have determined the genetic landscape of human α- and β-cells based on chromatin accessibility and transcript levels, which allowed for detection of novel α- and β-cell signature genes not previously known to be expressed in islets. Using fine-mapping of open chromatin, we have identified thousands of potential cis-regulatory elements that operate in an endocrine cell type-specific fashion.

  4. DNA typing of ancient parasite eggs from environmental samples identifies human and animal worm infections in Viking-age settlement

    DEFF Research Database (Denmark)

    Søe, Martin Jensen; Fredensborg, Brian Lund; Nejsum, Peter

    Human worm infections have, to a large extent, been eradicated in countries with high sanitary standards by preventing the fecal-oral transmission of infective eggs. It is possible to study parasite infections among past populations by retrieving and analyzing parasite eggs using paleoparasitolog......-age. Further, eggs of the Liver Fluke (Fasciola hepatica), whose primary hosts are cows and sheep, are identified indicating that grazing animals were kept in close proximity of the settlement....

  5. Integration of mouse and human genome-wide association data identifies KCNIP4 as an asthma gene.

    Directory of Open Access Journals (Sweden)

    Blanca E Himes

    Full Text Available Asthma is a common chronic respiratory disease characterized by airway hyperresponsiveness (AHR. The genetics of asthma have been widely studied in mouse and human, and homologous genomic regions have been associated with mouse AHR and human asthma-related phenotypes. Our goal was to identify asthma-related genes by integrating AHR associations in mouse with human genome-wide association study (GWAS data. We used Efficient Mixed Model Association (EMMA analysis to conduct a GWAS of baseline AHR measures from males and females of 31 mouse strains. Genes near or containing SNPs with EMMA p-values <0.001 were selected for further study in human GWAS. The results of the previously reported EVE consortium asthma GWAS meta-analysis consisting of 12,958 diverse North American subjects from 9 study centers were used to select a subset of homologous genes with evidence of association with asthma in humans. Following validation attempts in three human asthma GWAS (i.e., Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG and two human AHR GWAS (i.e., SHARP, DAG, the Kv channel interacting protein 4 (KCNIP4 gene was identified as nominally associated with both asthma and AHR at a gene- and SNP-level. In EVE, the smallest KCNIP4 association was at rs6833065 (P-value 2.9e-04, while the strongest associations for Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG were 1.5e-03, 1.0e-03, 3.1e-03 at rs7664617, rs4697177, rs4696975, respectively. At a SNP level, the strongest association across all asthma GWAS was at rs4697177 (P-value 1.1e-04. The smallest P-values for association with AHR were 2.3e-03 at rs11947661 in SHARP and 2.1e-03 at rs402802 in DAG. Functional studies are required to validate the potential involvement of KCNIP4 in modulating asthma susceptibility and/or AHR. Our results suggest that a useful approach to identify genes associated with human asthma is to leverage mouse AHR association data.

  6. Random small interfering RNA library screen identifies siRNAs that induce human erythroleukemia cell differentiation.

    Science.gov (United States)

    Fan, Cuiqing; Xiong, Yuan; Zhu, Ning; Lu, Yabin; Zhang, Jiewen; Wang, Song; Liang, Zicai; Shen, Yan; Chen, Meihong

    2011-03-01

    Cancers are characterized by poor differentiation. Differentiation therapy is a strategy to alleviate malignant phenotypes by inducing cancer cell differentiation. Here we carried out a combinatorial high-throughput screen with a random siRNA library on human erythroleukemia K-562 cell differentiation. Two siRNAs screened from the library were validated to be able to induce erythroid differentiation to varying degrees, determined by CD235 and globin up-regulation, GATA-2 down-regulation, and cell growth inhibition. The screen we performed here is the first trial of screening cancer differentiation-inducing agents from a random siRNA library, demonstrating that a random siRNA library can be considered as a new resource in efforts to seek new therapeutic agents for cancers. As a random siRNA library has a broad coverage for the entire genome, including known/unknown genes and protein coding/non-coding sequences, screening using a random siRNA library can be expected to greatly augment the repertoire of therapeutic siRNAs for cancers.

  7. Immunochip analysis identifies association of the RAD50/IL13 region with human longevity

    DEFF Research Database (Denmark)

    Flachsbart, Friederike; Ellinghaus, David; Gentschew, Liljana

    2016-01-01

    Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long-lived individuals (LLI) and 8919 younger controls....... First, we performed a large-scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune-associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip...... (1257 LLI, mean age 102.4 years; 1811 controls, mean age 49.1 years) and Denmark (493 LLI, mean age 96.2 years; 740 controls, mean age 63.1 years). The association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant...

  8. Whole genome analysis of selected human and animal rotaviruses identified in Uganda from 2012 to 2014 reveals complex genome reassortment events between human, bovine, caprine and porcine strains.

    Science.gov (United States)

    Bwogi, Josephine; Jere, Khuzwayo C; Karamagi, Charles; Byarugaba, Denis K; Namuwulya, Prossy; Baliraine, Frederick N; Desselberger, Ulrich; Iturriza-Gomara, Miren

    2017-01-01

    Rotaviruses of species A (RVA) are a common cause of diarrhoea in children and the young of various other mammals and birds worldwide. To investigate possible interspecies transmission of RVAs, whole genomes of 18 human and 6 domestic animal RVA strains identified in Uganda between 2012 and 2014 were sequenced using the Illumina HiSeq platform. The backbone of the human RVA strains had either a Wa- or a DS-1-like genetic constellation. One human strain was a Wa-like mono-reassortant containing a DS-1-like VP2 gene of possible animal origin. All eleven genes of one bovine RVA strain were closely related to those of human RVAs. One caprine strain had a mixed genotype backbone, suggesting that it emerged from multiple reassortment events involving different host species. The porcine RVA strains had mixed genotype backbones with possible multiple reassortant events with strains of human and bovine origin.Overall, whole genome characterisation of rotaviruses found in domestic animals in Uganda strongly suggested the presence of human-to animal RVA transmission, with concomitant circulation of multi-reassortant strains potentially derived from complex interspecies transmission events. However, whole genome data from the human RVA strains causing moderate and severe diarrhoea in under-fives in Uganda indicated that they were primarily transmitted from person-to-person.

  9. A RARE CASE OF IDENTIFICATION AND PRESERVATION OF HUMAN REMAINS. 240\tUn raro caso de identificación y preservación de restos humanos

    Directory of Open Access Journals (Sweden)

    Horacio E Solla

    2016-03-01

    black child that formed an unique soft tissue casting and to describe anthropological techniques used to identify the remains. The anthropological analysis indicated that she was black racial affinity, between 10-12-year old and was about150 cmof stature. Based on preliminary evidence that the victim might be Jane Doe, a victim of possible rape and murder, a digital superimposition was made using one victim's photograph and the unknown skull. This examination revealed that the skull corresponded consistently with the individual in the photograph. Results were supported by a DNA analysis. Therefore, forensic anthropology techniques can be successfully used in medico-legal investigations. 

  10. The transcriptional profiling of human in vivo-generated plasma cells identifies selective imbalances in monoclonal gammopathies.

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    Luis M Valor

    Full Text Available Plasma cells (PC represent the heterogeneous final stage of the B cells (BC differentiation process. To characterize the transition of BC into PC, transcriptomes from human naïve BC were compared to those of three functionally-different subsets of human in vivo-generated PC: i tonsil PC, mainly consisting of early PC; ii PC released to the blood after a potent booster-immunization (mostly cycling plasmablasts; and, iii bone marrow CD138+ PC that represent highly mature PC and include the long-lived PC compartment. This transcriptional transition involves subsets of genes related to key processes for PC maturation: the already known protein processing, apoptosis and homeostasis, and of new discovery including histones, macromolecule assembly, zinc-finger transcription factors and neuromodulation. This human PC signature is partially reproduced in vitro and is conserved in mouse. Moreover, the present study identifies genes that define PC subtypes (e.g., proliferation-associated genes for circulating PC and transcriptional-related genes for tonsil and bone marrow PC and proposes some putative transcriptional regulators of the human PC signatures (e.g., OCT/POU, XBP1/CREB, E2F, among others. Finally, we also identified a restricted imbalance of the present PC transcriptional program in monoclonal gammopathies that correlated with PC malignancy.

  11. Metabolomics Identifies Multiple Candidate Biomarkers to Diagnose and Stage Human African Trypanosomiasis.

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    Isabel M Vincent

    2016-12-01

    Full Text Available Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF. Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture. Here we use metabolomics to probe samples of CSF, plasma and urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different disease stages. Urine samples provided no robust markers indicative of infection or stage of infection due to inherent variability in urine concentrations. Biomarkers in CSF were able to distinguish patients at stage 1 or advanced stage 2 with absolute specificity. Eleven metabolites clearly distinguished the stage in most patients and two of these (neopterin and 5-hydroxytryptophan showed 100% specificity and sensitivity between our stage 1 and advanced stage 2 samples. Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible link to the eponymous symptoms of "sleeping sickness". Plasma also yielded several biomarkers clearly indicative of the presence (87% sensitivity and 95% specificity and stage of disease (92% sensitivity and 81% specificity. A logistic regression model including these metabolites showed clear separation of patients being either at stage 1 or advanced stage 2 or indeed diseased (both stages versus control.

  12. Pluripotent cell models of fanconi anemia identify the early pathological defect in human hemoangiogenic progenitors.

    Science.gov (United States)

    Suzuki, Naoya M; Niwa, Akira; Yabe, Miharu; Hira, Asuka; Okada, Chihiro; Amano, Naoki; Watanabe, Akira; Watanabe, Ken-Ichiro; Heike, Toshio; Takata, Minoru; Nakahata, Tatsutoshi; Saito, Megumu K

    2015-04-01

    Fanconi anemia (FA) is a disorder of genomic instability characterized by progressive bone marrow failure (BMF), developmental abnormalities, and an increased susceptibility to cancer. Although various consequences in hematopoietic stem/progenitor cells have been attributed to FA-BMF, the quest to identify the initial pathological event is still ongoing. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts of six patients with FA and FANCA mutations. An improved reprogramming method yielded iPSC-like colonies from all patients, and iPSC clones were propagated from two patients. Quantitative evaluation of the differentiation ability demonstrated that the differentiation propensity toward the hematopoietic and endothelial lineages is already defective in early hemoangiogenic progenitors. The expression levels of critical transcription factors were significantly downregulated in these progenitors. These data indicate that the hematopoietic consequences in FA patients originate from the early hematopoietic stage and highlight the potential usefulness of iPSC technology for elucidating the pathogenesis of FA-BMF. ©AlphaMed Press.

  13. A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure.

    Science.gov (United States)

    Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

    2016-05-17

    Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

  14. A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure

    Science.gov (United States)

    Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

    2016-05-01

    Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

  15. Transcriptome profiling of whole blood cells identifies PLEK2 and C1QB in human melanoma.

    Directory of Open Access Journals (Sweden)

    Yuchun Luo

    Full Text Available Developing analytical methodologies to identify biomarkers in easily accessible body fluids is highly valuable for the early diagnosis and management of cancer patients. Peripheral whole blood is a "nucleic acid-rich" and "inflammatory cell-rich" information reservoir and represents systemic processes altered by the presence of cancer cells.We conducted transcriptome profiling of whole blood cells from melanoma patients. To overcome challenges associated with blood-based transcriptome analysis, we used a PAXgene™ tube and NuGEN Ovation™ globin reduction system. The combined use of these systems in microarray resulted in the identification of 78 unique genes differentially expressed in the blood of melanoma patients. Of these, 68 genes were further analyzed by quantitative reverse transcriptase PCR using blood samples from 45 newly diagnosed melanoma patients (stage I to IV and 50 healthy control individuals. Thirty-nine genes were verified to be differentially expressed in blood samples from melanoma patients. A stepwise logit analysis selected eighteen 2-gene signatures that distinguish melanoma from healthy controls. Of these, a 2-gene signature consisting of PLEK2 and C1QB led to the best result that correctly classified 93.3% melanoma patients and 90% healthy controls. Both genes were upregulated in blood samples of melanoma patients from all stages. Further analysis using blood fractionation showed that CD45(- and CD45(+ populations were responsible for the altered expression levels of PLEK2 and C1QB, respectively.The current study provides the first analysis of whole blood-based transcriptome biomarkers for malignant melanoma. The expression of PLEK2, the strongest gene to classify melanoma patients, in CD45(- subsets illustrates the importance of analyzing whole blood cells for biomarker studies. The study suggests that transcriptome profiling of blood cells could be used for both early detection of melanoma and monitoring of patients

  16. Identifying black swans in NextGen: predicting human performance in off-nominal conditions.

    Science.gov (United States)

    Wickens, Christopher D; Hooey, Becky L; Gore, Brian F; Sebok, Angelia; Koenicke, Corey S

    2009-10-01

    The objective is to validate a computational model of visual attention against empirical data--derived from a meta-analysis--of pilots' failure to notice safety-critical unexpected events. Many aircraft accidents have resulted, in part, because of failure to notice nonsalient unexpected events outside of foveal vision, illustrating the phenomenon of change blindness. A model of visual noticing, N-SEEV (noticing-salience, expectancy, effort, and value), was developed to predict these failures. First, 25 studies that reported objective data on miss rate for unexpected events in high-fidelity cockpit simulations were identified, and their miss rate data pooled across five variables (phase of flight, event expectancy, event location, presence of a head-up display, and presence of a highway-in-the-sky display). Second, the parameters of the N-SEEV model were tailored to mimic these dichotomies. The N-SEEV model output predicted variance in the obtained miss rate (r = .73). The individual miss rates of all six dichotomous conditions were predicted within 14%, and four of these were predicted within 7%. The N-SEEV model, developed on the basis of an independent data set, was able to successfully predict variance in this safety-critical measure of pilot response to abnormal circumstances, as collected from the literature. As new technology and procedures are envisioned for the future airspace, it is important to predict if these may compromise safety in terms of pilots' failing to notice unexpected events. Computational models such as N-SEEV support cost-effective means of making such predictions.

  17. Combination of Multiple Spectral Libraries Improves the Current Search Methods Used to Identify Missing Proteins in the Chromosome-Centric Human Proteome Project.

    Science.gov (United States)

    Cho, Jin-Young; Lee, Hyoung-Joo; Jeong, Seul-Ki; Kim, Kwang-Youl; Kwon, Kyung-Hoon; Yoo, Jong Shin; Omenn, Gilbert S; Baker, Mark S; Hancock, William S; Paik, Young-Ki

    2015-12-04

    Approximately 2.9 billion long base-pair human reference genome sequences are known to encode some 20 000 representative proteins. However, 3000 proteins, that is, ~15% of all proteins, have no or very weak proteomic evidence and are still missing. Missing proteins may be present in rare samples in very low abundance or be only temporarily expressed, causing problems in their detection and protein profiling. In particular, some technical limitations cause missing proteins to remain unassigned. For example, current mass spectrometry techniques have high limits and error rates for the detection of complex biological samples. An insufficient proteome coverage in a reference sequence database and spectral library also raises major issues. Thus, the development of a better strategy that results in greater sensitivity and accuracy in the search for missing proteins is necessary. To this end, we used a new strategy, which combines a reference spectral library search and a simulated spectral library search, to identify missing proteins. We built the human iRefSPL, which contains the original human reference spectral library and additional peptide sequence-spectrum match entries from other species. We also constructed the human simSPL, which contains the simulated spectra of 173 907 human tryptic peptides determined by MassAnalyzer (version 2.3.1). To prove the enhanced analytical performance of the combination of the human iRefSPL and simSPL methods for the identification of missing proteins, we attempted to reanalyze the placental tissue data set (PXD000754). The data from each experiment were analyzed using PeptideProphet, and the results were combined using iProphet. For the quality control, we applied the class-specific false-discovery rate filtering method. All of the results were filtered at a false-discovery rate of libraries, iRefSPL and simSPL, were designed to ensure no overlap of the proteome coverage. They were shown to be complementary to spectral library

  18. Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker.

    Science.gov (United States)

    Ray, Partha; Rialon-Guevara, Kristy L; Veras, Emanuela; Sullenger, Bruce A; White, Rebekah R

    2012-05-01

    Most cases of pancreatic cancer are not diagnosed until they are no longer curable with surgery. Therefore, it is critical to develop a sensitive, preferably noninvasive, method for detecting the disease at an earlier stage. In order to identify biomarkers for pancreatic cancer, we devised an in vitro positive/negative selection strategy to identify RNA ligands (aptamers) that could detect structural differences between the secretomes of pancreatic cancer and non-cancerous cells. Using this molecular recognition approach, we identified an aptamer (M9-5) that differentially bound conditioned media from cancerous and non-cancerous human pancreatic cell lines. This aptamer further discriminated between the sera of pancreatic cancer patients and healthy volunteers with high sensitivity and specificity. We utilized biochemical purification methods and mass-spectrometric analysis to identify the M9-5 target as cyclophilin B (CypB). This molecular recognition-based strategy simultaneously identified CypB as a serum biomarker and generated a new reagent to recognize it in body fluids. Moreover, this approach should be generalizable to other diseases and complementary to traditional approaches that focus on differences in expression level between samples. Finally, we suggest that the aptamer we identified has the potential to serve as a tool for the early detection of pancreatic cancer.

  19. NCR1 Expression Identifies Canine Natural Killer Cell Subsets with Phenotypic Similarity to Human Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Jennifer Ann Foltz

    2016-11-01

    Full Text Available Canines spontaneously develop many cancers similar to humans - including osteosarcoma, leukemia, and lymphoma - offering the opportunity to study immune therapies in a genetically heterogeneous and immunocompetent environment. However, a lack of antibodies recognizing canine NK cell markers has resulted in suboptimal characterization and unknown purity of NK cell products, hindering the development of canine models of NK cell adoptive immunotherapy. To this end, we generated a novel antibody to canine NCR1 (NKp46, the putative species-wide marker of NK cells, enabling purification of NK cells for further characterization. We demonstrate that CD3-/NKp46+ cells in healthy and osteosarcoma-bearing canines have phenotypic similarity to human CD3-/NKp46+ NK cells, expressing mRNA for CD16 and the natural cytotoxicity receptors NKp30, NKp44, and NKp80. Functionally, we demonstrate with the calcein release assay that canine CD3-/NKp46+ cells kill canine tumor cell lines without prior sensitization and secrete IFN-γ, TNF-α, IL-8, IL-10, and GM-CSF as measured by Luminex. Like human NK cells, CD3-/NKp46+ cells expand rapidly on feeder cells expressing 4-1BBL and membrane-bound IL-21 (median= 20,283-fold in 21 days. Further, we identify a minor Null population (CD3-/CD21-/CD14-/NKp46- with reduced cytotoxicity against osteosarcoma cells, but similar cytokine secretion as CD3-/NKp46+ cells. Null cells in canines and humans have reduced expression of NKG2D, NKp44, and CD16 compared to NKp46+ NK cells, and can be induced to express NKp46 with further expansion on feeder cells. In conclusion, we have identified and characterized canine NK cells, including an NKp46- subset of canine and human NK cells, using a novel anti-canine NKp46 antibody, and report robust ex vivo expansion of canine NK cells sufficient for adoptive immunotherapy.

  20. A synthetic interaction screen identifies factors selectively required for proliferation and TERT transcription in p53-deficient human cancer cells.

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    Li Xie

    Full Text Available Numerous genetic and epigenetic alterations render cancer cells selectively dependent on specific genes and regulatory pathways, and represent potential vulnerabilities that can be therapeutically exploited. Here we describe an RNA interference (RNAi-based synthetic interaction screen to identify genes preferentially required for proliferation of p53-deficient (p53- human cancer cells. We find that compared to p53-competent (p53+ human cancer cell lines, diverse p53- human cancer cell lines are preferentially sensitive to loss of the transcription factor ETV1 and the DNA damage kinase ATR. In p53- cells, RNAi-mediated knockdown of ETV1 or ATR results in decreased expression of the telomerase catalytic subunit TERT leading to growth arrest, which can be reversed by ectopic TERT expression. Chromatin immunoprecipitation analysis reveals that ETV1 binds to a region downstream of the TERT transcriptional start-site in p53- but not p53+ cells. We find that the role of ATR is to phosphorylate and thereby stabilize ETV1. Our collective results identify a regulatory pathway involving ETV1, ATR, and TERT that is preferentially important for proliferation of diverse p53- cancer cells.

  1. Neanderthal infant and adult infracranial remains from Marillac (Charente, France).

    Science.gov (United States)

    Dolores Garralda, María; Maureille, Bruno; Vandermeersch, Bernard

    2014-09-01

    At the site of Marillac, near the Ligonne River in Marillac-le-Franc (Charente, France), a remarkable stratigraphic sequence has yielded a wealth of archaeological information, palaeoenvironmental data, as well as faunal and human remains. Marillac must have been a sinkhole used by Neanderthal groups as a hunting camp during MIS 4 (TL date 57,600 ± 4,600BP), where Quina Mousterian lithics and fragmented bones of reindeer predominate. This article describes three infracranial skeleton fragments. Two of them are from adults and consist of the incomplete shafts of a right radius (Marillac 24) and a left fibula (Marillac 26). The third fragment is the diaphysis of the right femur of an immature individual (Marillac 25), the size and shape of which resembles those from Teshik-Tash and could be assigned to a child of a similar age. The three fossils have been compared with the remains of other Neanderthals or anatomically Modern Humans (AMH). Furthermore, the comparison of the infantile femora, Marillac 25 and Teshik-Tash, with the remains of several European children from the early Middle Ages clearly demonstrates the robustness and rounded shape of both Neanderthal diaphyses. Evidence of peri-mortem manipulations have been identified on all three bones, with spiral fractures, percussion pits and, in the case of the radius and femur, unquestionable cutmarks made with flint implements, probably during defleshing. Traces of periostosis appear on the fibula fragment and on the immature femoral diaphysis, although their aetiology remains unknown. Copyright © 2014 Wiley Periodicals, Inc.

  2. A panel of microsatellites to individually identify leopards and its application to leopard monitoring in human dominated landscapes

    Directory of Open Access Journals (Sweden)

    Selvaraj Velu

    2009-12-01

    Full Text Available Abstract Background Leopards are the most widely distributed of the large cats, ranging from Africa to the Russian Far East. Because of habitat fragmentation, high human population densities and the inherent adaptability of this species, they now occupy landscapes close to human settlements. As a result, they are the most common species involved in human wildlife conflict in India, necessitating their monitoring. However, their elusive nature makes such monitoring difficult. Recent advances in DNA methods along with non-invasive sampling techniques can be used to monitor populations and individuals across large landscapes including human dominated ones. In this paper, we describe a DNA-based method for leopard individual identification where we used fecal DNA samples to obtain genetic material. Further, we apply our methods to non-invasive samples collected in a human-dominated landscape to estimate the minimum number of leopards in this human-leopard conflict area in Western India. Results In this study, 25 of the 29 tested cross-specific microsatellite markers showed positive amplification in 37 wild-caught leopards. These loci revealed varied levels of polymorphism (four-12 alleles and heterozygosity (0.05-0.79. Combining data on amplification success (including non-invasive samples and locus specific polymorphisms, we showed that eight loci provide a sibling probability of identity of 0.0005, suggesting that this panel can be used to discriminate individuals in the wild. When this microsatellite panel was applied to fecal samples collected from a human-dominated landscape, we identified 7 individuals, with a sibling probability of identity of 0.001. Amplification success of field collected scats was up to 72%, and genotype error ranged from 0-7.4%. Conclusion Our results demonstrated that the selected panel of eight microsatellite loci can conclusively identify leopards from various kinds of biological samples. Our methods can be used to

  3. Identifying Potential Areas of Human Zika Infection in the City of Los Angeles, California by Use of Remote Sensing Imagery

    Science.gov (United States)

    Lee, J.

    2017-12-01

    As of April 2017, California is the third most prevalent state on the United States for Zika Infection and Southern California has an ever growing population of Aedes mosquitos. Zika is a disease which poses a significant risk to humans and other mammals due to its effects on pregnancy. This emerging disease is highly contagious due to its spread of infection primarily by Aedes aegypti mosquitos. Aedes mosquitos are able to breed in small rain collecting containers which allow the species to persevere in urban and semi urban environments. We hope to identify potential areas with risk of human infection within Los Angeles and its surrounding areas. This study integrates remote sensing, GIS, statistical, and environmental techniques to study favorable habitats for this particular species of mosquitos and their larvae. The study of the geographic and landscape factors which promote the larvae development allow for the disease spread to be analyzed and modeled. There are several goals in the development of this study. These include the coordination of statistical data with local epidemiology departments, identify workflows to improve efficiency, create models which can be utilized for disease prevention, and identify geographic risk factors for the spread of Zika.

  4. MRI of Mouse Models for Gliomas Shows Similarities to Humans and Can Be Used to Identify Mice for Preclinical Trials

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    Jason A. Koutcher

    2002-01-01

    Full Text Available Magnetic resonance imaging (MRI has been utilized for screening and detecting brain tumors in mice based upon their imaging characteristics appearance and their pattern of enhancement. Imaging of these tumors reveals many similarities to those observed in humans with identical pathology. Specifically, high-grade murine gliomas have histologic characteristics of glioblastoma multiforme (GBM with contrast enhancement after intravenous administration of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA, implying disruption of the blood-brain barrier in these tumors. In contrast, low-grade murine oligodendrogliomas do not reveal contrast enhancement, similar to human tumors. MRI can be used to identify mice with brain neoplasms as inclusion criteria in preclinical trials.

  5. New STLV-3 strains and a divergent SIVmus strain identified in non-human primate bushmeat in Gabon

    Directory of Open Access Journals (Sweden)

    Liégeois Florian

    2012-03-01

    Full Text Available Abstract Background Human retroviral infections such as Human Immunodeficiency Virus (HIV or Human T-cell Lymphotropic Virus (HTLV are the result of simian zoonotic transmissions through handling and butchering of Non-Human Primates (NHP or by close contact with pet animals. Recent studies on retroviral infections in NHP bushmeat allowed for the identification of numerous Simian Immunodeficiency Viruses (SIV and Simian T-cell Lymphotropic Viruses (STLV to which humans are exposed. Nevertheless, today, data on simian retroviruses at the primate/hunter interface remain scarce. We conducted a pilot study on 63 blood and/or tissues samples derived from NHP bushmeat seized by the competent authorities in different locations across the country. Results SIV and STLV were detected by antibodies to HIV and HTLV antigens, and PCRs were performed on samples with an HIV or/and HTLV-like or indeterminate profile. Fourteen percent of the samples cross-reacted with HIV antigens and 44% with HTLV antigens. We reported STLV-1 infections in five of the seven species tested. STLV-3 infections, including a new STLV-3 subtype, STLV-1 and -3 co-infections, and triple SIV, STLV-1, STLV-3 infections were observed in red-capped mangabeys (C.torquatus. We confirmed SIV infections by PCR and sequence analyses in mandrills, red-capped mangabeys and showed that mustached monkeys in Gabon are infected with a new SIV strain basal to the SIVgsn/mus/mon lineage that did not fall into the previously described SIVmus lineages reported from the corresponding species in Cameroon. The same monkey (subspecies can thus be carrier of, at least, three distinct SIVs. Overall, the minimal prevalence observed for both STLV and SIV natural infections were 26.9% and 11.1% respectively. Conclusions Overall, these data, obtained from a restricted sampling, highlight the need for further studies on simian retroviruses in sub-Saharan Africa to better understand their evolutionary history and to

  6. Mining the Human Complexome Database Identifies RBM14 as an XPO1-Associated Protein Involved in HIV-1 Rev Function

    OpenAIRE

    Budhiraja, Sona; Liu, Hongbing; Couturier, Jacob; Malovannaya, Anna; Qin, Jun; Lewis, Dorothy E.; Rice, Andrew P.

    2015-01-01

    By recruiting the host protein XPO1 (CRM1), the HIV-1 Rev protein mediates the nuclear export of incompletely spliced viral transcripts. We mined data from the recently described human nuclear complexome to identify a host protein, RBM14, which associates with XPO1 and Rev and is involved in Rev function. Using a Rev-dependent p24 reporter plasmid, we found that RBM14 depletion decreased Rev activity and Rev-mediated enhancement of the cytoplasmic levels of unspliced viral transcripts. RBM14 ...

  7. DNA typing of ancient parasite eggs from environmental samples identifies human and animal worm infections in viking-age settlement

    DEFF Research Database (Denmark)

    Søe, Martin Jensen; Nejsum, Peter; Fredensborg, Brian Lund

    2015-01-01

    Ancient parasite eggs were recovered from environmental samples collected at a Viking-age settlement in Viborg, Denmark, dated 1018-1030 A.D. Morphological examination identified Ascaris sp., Trichuris sp., and Fasciola sp. eggs, but size and shape did not allow species identification. By carefully...... selecting genetic markers, PCR amplification and sequencing of ancient DNA (aDNA) isolates resulted in identification of: the human whipworm, Trichuris trichiura, using SSUrRNA sequence homology; Ascaris sp. with 100% homology to cox1 haplotype 07; and Fasciola hepatica using ITS1 sequence homology...

  8. A human reliability analysis (HRA) method for identifying and assessing the error of commission (EOC) from a diagnosis failure

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Whan; Jung, Won Dea; Park, Jin Yun; Kang, Dae Il

    2005-01-01

    The study deals with a method for systematically identifying and assessing the EOC events that might be caused from a diagnosis failure or misdiagnosis of the expected events in accident scenarios of nuclear power plants. The method for EOC identification and assessment consists of three steps: analysis of the potential for a diagnosis failure (or misdiagnosis), identification of the EOC events from the diagnosis failure, quantitative assessment of the identified EOC events. As a tool for analysing a diagnosis failure, the MisDiagnosis Tree Analysis (MDTA) technique is proposed with the taxonomy of misdiagnosis causes. Also, the guidance on the identification of EOC events and the classification system and data are given for quantitiative assessment. As an applicaton of the proposed method, the EOCs identification and assessment for Younggwang 3 and 4 plants and their impact on the plant risk were performed. As the result, six events or event sequences were considered for diagnosis failures and about 20 new Human Failure Events (HFEs) involving EOCs were identified. According to the assessment of the risk impact of the identified HFEs, they increase the CDF by 11.4 % of the current CDF value, which corresponds to 10.2 % of the new CDF. The small loss of coolant accident (SLOCA) turned out to be a major contributor to the increase of CDF resulting in 9.2 % increaseof the current CDF.

  9. A robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Je-Hyuk Lee

    2009-11-01

    Full Text Available Normal variation in gene expression due to regulatory polymorphisms is often masked by biological and experimental noise. In addition, some regulatory polymorphisms may become apparent only in specific tissues. We derived human induced pluripotent stem (iPS cells from adult skin primary fibroblasts and attempted to detect tissue-specific cis-regulatory variants using in vitro cell differentiation. We used padlock probes and high-throughput sequencing for digital RNA allelotyping and measured allele-specific gene expression in primary fibroblasts, lymphoblastoid cells, iPS cells, and their differentiated derivatives. We show that allele-specific expression is both cell type and genotype-dependent, but the majority of detectable allele-specific expression loci remains consistent despite large changes in the cell type or the experimental condition following iPS reprogramming, except on the X-chromosome. We show that our approach to mapping cis-regulatory variants reduces in vitro experimental noise and reveals additional tissue-specific variants using skin-derived human iPS cells.

  10. Transcriptional profiling of human monocytes identifies the inhibitory receptor CD300a as regulator of transendothelial migration.

    Directory of Open Access Journals (Sweden)

    Sharang Ghavampour

    Full Text Available Local inflammatory responses are characterized by the recruitment of circulating leukocytes from the blood to sites of inflammation, a process requiring the directed migration of leukocytes across the vessel wall and hence a penetration of the endothelial lining. To identify underlying signalling events and novel factors involved in these processes we screened for genes differentially expressed in human monocytes following their adhesion to and passage through an endothelial monolayer. Functional annotation clustering of the genes identified revealed an overrepresentation of those associated with inflammation/immune response, in particular early monocyte to macrophage differentiation. Among the gene products so far not implicated in monocyte transendothelial migration was the inhibitory immune receptor CD300a. CD300a mRNA and protein levels were upregulated following transmigration and engagement of the receptor by anti-CD300a antibodies markedly reduced monocyte transendothelial migration. In contrast, siRNA mediated downregulation of CD300a in human monocytes increased their rate of migration. CD300a colocalized and cosedimented with actin filaments and, when activated, caused F-actin cytoskeleton alterations. Thus, monocyte transendothelial migration is accompanied by an elevation of CD300a which serves an inhibitory function possibly required for termination of the actual transmigration.

  11. Diagnostic Accuracy of Periapical Radiography and Cone-beam Computed Tomography in Identifying Root Canal Configuration of Human Premolars.

    Science.gov (United States)

    Sousa, Thiago Oliveira; Haiter-Neto, Francisco; Nascimento, Eduarda Helena Leandro; Peroni, Leonardo Vieira; Freitas, Deborah Queiroz; Hassan, Bassam

    2017-07-01

    The aim of this study was to assess the diagnostic accuracy of periapical radiography (PR) and cone-beam computed tomographic (CBCT) imaging in the detection of the root canal configuration (RCC) of human premolars. PR and CBCT imaging of 114 extracted human premolars were evaluated by 2 oral radiologists. RCC was recorded according to Vertucci's classification. Micro-computed tomographic imaging served as the gold standard to determine RCC. Accuracy, sensitivity, specificity, and predictive values were calculated. The Friedman test compared both PR and CBCT imaging with the gold standard. CBCT imaging showed higher values for all diagnostic tests compared with PR. Accuracy was 0.55 and 0.89 for PR and CBCT imaging, respectively. There was no difference between CBCT imaging and the gold standard, whereas PR differed from both CBCT and micro-computed tomographic imaging (P < .0001). CBCT imaging was more accurate than PR for evaluating different types of RCC individually. Canal configuration types III, VII, and "other" were poorly identified on CBCT imaging with a detection accuracy of 50%, 0%, and 43%, respectively. With PR, all canal configurations except type I were poorly visible. PR presented low performance in the detection of RCC in premolars, whereas CBCT imaging showed no difference compared with the gold standard. Canals with complex configurations were less identifiable using both imaging methods, especially PR. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  12. Integration of ATAC-seq and RNA-seq identifies human alpha cell and beta cell signature genes.

    Science.gov (United States)

    Ackermann, Amanda M; Wang, Zhiping; Schug, Jonathan; Naji, Ali; Kaestner, Klaus H

    2016-03-01

    Although glucagon-secreting α-cells and insulin-secreting β-cells have opposing functions in regulating plasma glucose levels, the two cell types share a common developmental origin and exhibit overlapping transcriptomes and epigenomes. Notably, destruction of β-cells can stimulate repopulation via transdifferentiation of α-cells, at least in mice, suggesting plasticity between these cell fates. Furthermore, dysfunction of both α- and β-cells contributes to the pathophysiology of type 1 and type 2 diabetes, and β-cell de-differentiation has been proposed to contribute to type 2 diabetes. Our objective was to delineate the molecular properties that maintain islet cell type specification yet allow for cellular plasticity. We hypothesized that correlating cell type-specific transcriptomes with an atlas of open chromatin will identify novel genes and transcriptional regulatory elements such as enhancers involved in α- and β-cell specification and plasticity. We sorted human α- and β-cells and performed the "Assay for Transposase-Accessible Chromatin with high throughput sequencing" (ATAC-seq) and mRNA-seq, followed by integrative analysis to identify cell type-selective gene regulatory regions. We identified numerous transcripts with either α-cell- or β-cell-selective expression and discovered the cell type-selective open chromatin regions that correlate with these gene activation patterns. We confirmed cell type-selective expression on the protein level for two of the top hits from our screen. The "group specific protein" (GC; or vitamin D binding protein) was restricted to α-cells, while CHODL (chondrolectin) immunoreactivity was only present in β-cells. Furthermore, α-cell- and β-cell-selective ATAC-seq peaks were identified to overlap with known binding sites for islet transcription factors, as well as with single nucleotide polymorphisms (SNPs) previously identified as risk loci for type 2 diabetes. We have determined the genetic landscape of

  13. Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

    Directory of Open Access Journals (Sweden)

    Hongzhe Li

    2014-12-01

    Full Text Available Human bone marrow (BM contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs, which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show that low/negative expression of CD140a (PDGFR-α on lin−/CD45−/CD271+ BM cells identified a cell population with very high MSC activity, measured as fibroblastic colony-forming unit frequency and typical in vitro and in vivo stroma formation and differentiation capacities. Furthermore, these cells exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin−/CD45−/CD271+/CD140alow/− cells effectively mediated the ex vivo expansion of transplantable CD34+ hematopoietic stem cells. Taken together, these data indicate that CD140a is a key negative selection marker for adult human BM-MSCs, which enables to prospectively isolate a close to pure population of candidate human adult stroma stem/progenitor cells with potent hematopoiesis-supporting capacity.

  14. Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity

    International Nuclear Information System (INIS)

    Axon, Andrew; May, Felicity E.B.; Gaughan, Luke E.; Williams, Faith M.; Blain, Peter G.; Wright, Matthew C.

    2012-01-01

    Primary biliary cirrhosis (PBC) is a cholestatic liver disease of unknown cause that occurs most frequently in post-menopausal women. Since the female sex hormone oestrogen can be cholestatic, we hypothesised that PBC may be triggered in part by chronic exposure to xenoestrogens (which may be more active on a background of low endogenous oestrogen levels seen in post-menopausal women). A reporter gene construct employing a synthetic oestrogen response element predicted to specifically interact with oestrogen receptors (ER) was constructed. Co-transfection of this reporter into an ER null cell line with a variety of nuclear receptor expression constructs indicated that the reporter gene was trans-activated by ERα and ERβ, but not by the androgen, thyroid, progesterone, glucocorticoid or vitamin D receptors. Chemicals linked to PBC were then screened for xenoestrogen activity in the human ERα-positive MCF-7 breast cancer cell line. Using this assay, the coal-derived food and cosmetic colourings – sunset yellow and tartrazine – were identified as novel human ERα activators, activating the human ER with an EC 50% concentration of 220 and 160 nM, respectively.

  15. Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity.

    Science.gov (United States)

    Axon, Andrew; May, Felicity E B; Gaughan, Luke E; Williams, Faith M; Blain, Peter G; Wright, Matthew C

    2012-08-16

    Primary biliary cirrhosis (PBC) is a cholestatic liver disease of unknown cause that occurs most frequently in post-menopausal women. Since the female sex hormone oestrogen can be cholestatic, we hypothesised that PBC may be triggered in part by chronic exposure to xenoestrogens (which may be more active on a background of low endogenous oestrogen levels seen in post-menopausal women). A reporter gene construct employing a synthetic oestrogen response element predicted to specifically interact with oestrogen receptors (ER) was constructed. Co-transfection of this reporter into an ER null cell line with a variety of nuclear receptor expression constructs indicated that the reporter gene was trans-activated by ERα and ERβ, but not by the androgen, thyroid, progesterone, glucocorticoid or vitamin D receptors. Chemicals linked to PBC were then screened for xenoestrogen activity in the human ERα-positive MCF-7 breast cancer cell line. Using this assay, the coal-derived food and cosmetic colourings--sunset yellow and tartrazine--were identified as novel human ERα activators, activating the human ER with an EC(50%) concentration of 220 and 160 nM, respectively. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis.

    Science.gov (United States)

    Yang, Fan; Wang, Jiebiao; Pierce, Brandon L; Chen, Lin S

    2017-11-01

    The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes ( cis -eQTLs). More research is needed to identify effects of genetic variation on distant genes ( trans -eQTLs) and understand their biological mechanisms. One common trans -eQTLs mechanism is "mediation" by a local ( cis ) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are " cis -mediators" of trans -eQTLs, including those " cis -hubs" involved in regulation of many trans -genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans -eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis -mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis -hubs and trans -eQTL regulation across tissue types. © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

  17. Identifying Spatial Units of Human Occupation in the Brazilian Amazon Using Landsat and CBERS Multi-Resolution Imagery

    Directory of Open Access Journals (Sweden)

    Maria Isabel Sobral Escada

    2012-01-01

    Full Text Available Every spatial unit of human occupation is part of a network structuring an extensive process of urbanization in the Amazon territory. Multi-resolution remote sensing data were used to identify and map human presence and activities in the Sustainable Forest District of Cuiabá-Santarém highway (BR-163, west of Pará, Brazil. The limits of spatial units of human occupation were mapped based on digital classification of Landsat-TM5 (Thematic Mapper 5 image (30m spatial resolution. High-spatial-resolution CBERS-HRC (China-Brazil Earth Resources Satellite-High-Resolution Camera images (5 m merged with CBERS-CCD (Charge Coupled Device images (20 m were used to map spatial arrangements inside each populated unit, describing intra-urban characteristics. Fieldwork data validated and refined the classification maps that supported the categorization of the units. A total of 133 spatial units were individualized, comprising population centers as municipal seats, villages and communities, and units of human activities, such as sawmills, farmhouses, landing strips, etc. From the high-resolution analysis, 32 population centers were grouped in four categories, described according to their level of urbanization and spatial organization as: structured, recent, established and dependent on connectivity. This multi-resolution approach provided spatial information about the urbanization process and organization of the territory. It may be extended into other areas or be further used to devise a monitoring system, contributing to the discussion of public policy priorities for sustainable development in the Amazon.

  18. Elevated osteopontin and thrombospondin expression identifies malignant human breast carcinoma but is not indicative of metastatic status

    International Nuclear Information System (INIS)

    Wang-Rodriguez, Jessica; Urquidi, Virginia; Rivard, Amber; Goodison, Steve

    2003-01-01

    Our previous characterization of a human breast tumor metastasis model identified several candidate metastasis genes. The expression of osteopontin (OPN) correlated with the metastatic phenotype, whereas thrombospondin-1 (TSP-1) and tyrosinase-related protein-1 (TYRP-1) correlated with the nonmetastatic phenotype of independent MDA-MB-435 cell lines implanted orthotopically into athymic mice. The aim of the present study was to examine the cellular distribution of these molecules in human breast tissue and to determine whether the relative expression level of these three genes is associated with human breast tumor metastasis. Sixty-eight fresh, frozen specimens including 31 primary infiltrating ductal carcinomas, 22 nodal metastases, 10 fibroadenomas, and five normal breast tissues were evaluated for OPN expression, TSP-1 expression and TYRP-1 expression. Immunohistochemistry was performed to monitor the cellular distribution and to qualitatively assess expression. Quantitative analysis was achieved by enrichment of breast epithelial cells using laser-capture microdissection and subsequent real-time, quantitative PCR. The epithelial components of the breast tissue were the source of OPN and TSP-1 expression, whereas TYRP-1 was present in both the epithelial and stromal components. Both OPN and TSP-1 expression were significantly higher in malignant epithelial sources over normal and benign epithelial sources, but no difference in expression levels was evident between primary tumors with or without metastases, nor between primary and metastatic carcinomas. Elevated expression of OPN and TSP-1 may play a role in the pathogenesis of breast cancer. The multiplex analysis of these molecules may enhance our ability to diagnose and/or prognosticate human breast malignancy

  19. Who’s Who at the Border? A rights-based approach to identifying human trafficking at international borders

    Directory of Open Access Journals (Sweden)

    Marika McAdam

    2013-09-01

    Full Text Available International borders are widely touted as bastions in the fight against trafficking in persons. This article acknowledges the important role border officials play in preventing human trafficking, but calls for expectations to be tempered by deference to the conceptual complexity of cross-border trafficking and the migration processes involved. The fact that many trafficked victims begin their journeys as irregular or smuggled migrants highlights the challenge posed to border officials in identifying trafficked persons among the people they encounter. Indicators of trafficking generally relate to the exploitation phase, leaving border officials with little guidance as to how persons vulnerable to trafficking can be accurately identified before any exploitation has occurred. Ultimately, this paper advocates a pragmatic rights-based approach in designating anti-trafficking functions to border officials. A rights-based approach to border control acknowledges the core work of border officials as being to uphold border integrity, while ensuring that their performance of this role does not jeopardise the rights of those they intercept nor result in missed opportunities for specialists to identify trafficked persons and other vulnerable people among them.

  20. Validation of case-finding algorithms derived from administrative data for identifying adults living with human immunodeficiency virus infection.

    Directory of Open Access Journals (Sweden)

    Tony Antoniou

    Full Text Available OBJECTIVE: We sought to validate a case-finding algorithm for human immunodeficiency virus (HIV infection using administrative health databases in Ontario, Canada. METHODS: We constructed 48 case-finding algorithms using combinations of physician billing claims, hospital and emergency room separations and prescription drug claims. We determined the test characteristics of each algorithm over various time frames for identifying HIV infection, using data abstracted from the charts of 2,040 randomly selected patients receiving care at two medical practices in Toronto, Ontario as the reference standard. RESULTS: With the exception of algorithms using only a single physician claim, the specificity of all algorithms exceeded 99%. An algorithm consisting of three physician claims over a three year period had a sensitivity and specificity of 96.2% (95% CI 95.2%-97.9% and 99.6% (95% CI 99.1%-99.8%, respectively. Application of the algorithm to the province of Ontario identified 12,179 HIV-infected patients in care for the period spanning April 1, 2007 to March 31, 2009. CONCLUSIONS: Case-finding algorithms generated from administrative data can accurately identify adults living with HIV. A relatively simple "3 claims in 3 years" definition can be used for assembling a population-based cohort and facilitating future research examining trends in health service use and outcomes among HIV-infected adults in Ontario.

  1. Shotgun microbial profiling of fossil remains

    DEFF Research Database (Denmark)

    Der Sarkissian, Clio; Ermini, Luca; Jónsson, Hákon

    2014-01-01

    the specimen of interest, but instead reflect environmental organisms that colonized the specimen after death. Here, we characterize the microbial diversity recovered from seven c. 200- to 13 000-year-old horse bones collected from northern Siberia. We use a robust, taxonomy-based assignment approach...... to identify the microorganisms present in ancient DNA extracts and quantify their relative abundance. Our results suggest that molecular preservation niches exist within ancient samples that can potentially be used to characterize the environments from which the remains are recovered. In addition, microbial...... community profiling of the seven specimens revealed site-specific environmental signatures. These microbial communities appear to comprise mainly organisms that colonized the fossils recently. Our approach significantly extends the amount of useful data that can be recovered from ancient specimens using...

  2. Transcriptional profiling of human liver identifies sex-biased genes associated with polygenic dyslipidemia and coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Yijing Zhang

    Full Text Available Sex-differences in human liver gene expression were characterized on a genome-wide scale using a large liver sample collection, allowing for detection of small expression differences with high statistical power. 1,249 sex-biased genes were identified, 70% showing higher expression in females. Chromosomal bias was apparent, with female-biased genes enriched on chrX and male-biased genes enriched on chrY and chr19, where 11 male-biased zinc-finger KRAB-repressor domain genes are distributed in six clusters. Top biological functions and diseases significantly enriched in sex-biased genes include transcription, chromatin organization and modification, sexual reproduction, lipid metabolism and cardiovascular disease. Notably, sex-biased genes are enriched at loci associated with polygenic dyslipidemia and coronary artery disease in genome-wide association studies. Moreover, of the 8 sex-biased genes at these loci, 4 have been directly linked to monogenic disorders of lipid metabolism and show an expression profile in females (elevated expression of ABCA1, APOA5 and LDLR; reduced expression of LIPC that is consistent with the lower female risk of coronary artery disease. Female-biased expression was also observed for CYP7A1, which is activated by drugs used to treat hypercholesterolemia. Several sex-biased drug-metabolizing enzyme genes were identified, including members of the CYP, UGT, GPX and ALDH families. Half of 879 mouse orthologs, including many genes of lipid metabolism and homeostasis, show growth hormone-regulated sex-biased expression in mouse liver, suggesting growth hormone might play a similar regulatory role in human liver. Finally, the evolutionary rate of protein coding regions for human-mouse orthologs, revealed by dN/dS ratio, is significantly higher for genes showing the same sex-bias in both species than for non-sex-biased genes. These findings establish that human hepatic sex differences are widespread and affect diverse cell

  3. Expression and functional assessment of candidate type 2 diabetes susceptibility genes identify four new genes contributing to human insulin secretion

    Directory of Open Access Journals (Sweden)

    Fatou K. Ndiaye

    2017-06-01

    Full Text Available Objectives: Genome-wide association studies (GWAS have identified >100 loci independently contributing to type 2 diabetes (T2D risk. However, translational implications for precision medicine and for the development of novel treatments have been disappointing, due to poor knowledge of how these loci impact T2D pathophysiology. Here, we aimed to measure the expression of genes located nearby T2D associated signals and to assess their effect on insulin secretion from pancreatic beta cells. Methods: The expression of 104 candidate T2D susceptibility genes was measured in a human multi-tissue panel, through PCR-free expression assay. The effects of the knockdown of beta-cell enriched genes were next investigated on insulin secretion from the human EndoC-βH1 beta-cell line. Finally, we performed RNA-sequencing (RNA-seq so as to assess the pathways affected by the knockdown of the new genes impacting insulin secretion from EndoC-βH1, and we analyzed the expression of the new genes in mouse models with altered pancreatic beta-cell function. Results: We found that the candidate T2D susceptibility genes' expression is significantly enriched in pancreatic beta cells obtained by laser capture microdissection or sorted by flow cytometry and in EndoC-βH1 cells, but not in insulin sensitive tissues. Furthermore, the knockdown of seven T2D-susceptibility genes (CDKN2A, GCK, HNF4A, KCNK16, SLC30A8, TBC1D4, and TCF19 with already known expression and/or function in beta cells changed insulin secretion, supporting our functional approach. We showed first evidence for a role in insulin secretion of four candidate T2D-susceptibility genes (PRC1, SRR, ZFAND3, and ZFAND6 with no previous knowledge of presence and function in beta cells. RNA-seq in EndoC-βH1 cells with decreased expression of PRC1, SRR, ZFAND6, or ZFAND3 identified specific gene networks related to T2D pathophysiology. Finally, a positive correlation between the expression of Ins2 and the

  4. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    International Nuclear Information System (INIS)

    Kleinstreuer, N.C.; Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R.; Weir-Hauptman, A.M.; Palmer, J.A.; Knudsen, T.B.; Dix, D.J.; Donley, E.L.R.; Cezar, G.G.

    2011-01-01

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox® model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: ► We tested 11 environmental compounds in a hESC metabolomics platform. ► Significant changes in secreted small molecule metabolites were observed. ► Perturbed mass features map to pathways critical for normal development and pregnancy. ► Arginine, proline, nicotinate, nicotinamide and glutathione pathways were affected.

  5. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Kleinstreuer, N.C., E-mail: kleinstreuer.nicole@epa.gov [NCCT, US EPA, RTP, NC 27711 (United States); Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Weir-Hauptman, A.M. [Covance, Inc., Madison, WI 53704 (United States); Palmer, J.A. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Knudsen, T.B.; Dix, D.J. [NCCT, US EPA, RTP, NC 27711 (United States); Donley, E.L.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Cezar, G.G. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); University of Wisconsin-Madison, Madison, WI 53706 (United States)

    2011-11-15

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast Trade-Mark-Sign chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox Registered-Sign model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: Black-Right-Pointing-Pointer We tested 11 environmental compounds in a hESC metabolomics platform. Black-Right-Pointing-Pointer Significant changes in secreted small molecule metabolites were observed. Black-Right-Pointing-Pointer Perturbed mass features map to pathways critical for normal

  6. Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

    DEFF Research Database (Denmark)

    Li, Hongzhe; Ghazanfari, Roshanak; Zacharaki, Dimitra

    2014-01-01

    Human bone marrow (BM) contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs), which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show...... exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin(-)/CD45(-)/CD271(+)/CD140a(low/-) cells effectively mediated the ex vivo expansion of transplantable CD34(+) hematopoietic stem cells. Taken together, these data indicate that CD140a is a key...... that low/negative expression of CD140a (PDGFR-α) on lin(-)/CD45(-)/CD271(+) BM cells identified a cell population with very high MSC activity, measured as fibroblastic colony-forming unit frequency and typical in vitro and in vivo stroma formation and differentiation capacities. Furthermore, these cells...

  7. Functional requirements for the man-vehicle systems research facility. [identifying and correcting human errors during flight simulation

    Science.gov (United States)

    Clement, W. F.; Allen, R. W.; Heffley, R. K.; Jewell, W. F.; Jex, H. R.; Mcruer, D. T.; Schulman, T. M.; Stapleford, R. L.

    1980-01-01

    The NASA Ames Research Center proposed a man-vehicle systems research facility to support flight simulation studies which are needed for identifying and correcting the sources of human error associated with current and future air carrier operations. The organization of research facility is reviewed and functional requirements and related priorities for the facility are recommended based on a review of potentially critical operational scenarios. Requirements are included for the experimenter's simulation control and data acquisition functions, as well as for the visual field, motion, sound, computation, crew station, and intercommunications subsystems. The related issues of functional fidelity and level of simulation are addressed, and specific criteria for quantitative assessment of various aspects of fidelity are offered. Recommendations for facility integration, checkout, and staffing are included.

  8. Small molecule inhibitors of the LEDGF site of human immunodeficiency virus integrase identified by fragment screening and structure based design.

    Directory of Open Access Journals (Sweden)

    Thomas S Peat

    Full Text Available A fragment-based screen against human immunodeficiency virus type 1 (HIV integrase led to a number of compounds that bound to the lens epithelium derived growth factor (LEDGF binding site of the integrase catalytic core domain. We determined the crystallographic structures of complexes of the HIV integrase catalytic core domain for 10 of these compounds and quantitated the binding by surface plasmon resonance. We demonstrate that the compounds inhibit the interaction of LEDGF with HIV integrase in a proximity AlphaScreen assay, an assay for the LEDGF enhancement of HIV integrase strand transfer and in a cell based assay. The compounds identified represent a potential framework for the development of a new series of HIV integrase inhibitors that do not bind to the catalytic site of the enzyme.

  9. RNA-seq methods for identifying differentially expressed gene in human pancreatic islet cells treated with pro-inflammatory cytokines.

    Science.gov (United States)

    Li, Bo; Bi, Chang Long; Lang, Ning; Li, Yu Ze; Xu, Chao; Zhang, Ying Qi; Zhai, Ai Xia; Cheng, Zhi Feng

    2014-01-01

    Type 1 diabetes is a chronic autoimmune disease in which pancreatic beta cells are killed by the infiltrating immune cells as well as the cytokines released by these cells. Many studies indicate that inflammatory mediators have an essential role in this disease. In the present study, we profiled the transcriptome in human islets of langerhans under control conditions or following exposure to the pro-inflammatory cytokines based on the RNA sequencing dataset downloaded from SRA database. After filtered the low-quality ones, the RNA readers was aligned to human genome hg19 by TopHat and then assembled by Cufflinks. The expression value of each transcript was calculated and consequently differentially expressed genes were screened out. Finally, a total of 63 differentially expressed genes were identified including 60 up-regulated and three down-regulated genes. GBP5 and CXCL9 stood out as the top two most up-regulated genes in cytokines treated samples with the log2 fold change of 12.208 and 10.901, respectively. Meanwhile, PTF1A and REG3G were identified as the top two most down-regulated genes with the log2 fold change of -3.759 and -3.606, respectively. Of note, we also found 262 lncRNAs (long non-coding RNA), 177 of which were inferred as novel lncRNAs. Further in-depth follow-up analysis of the transcriptional regulation reported in this study may shed light on the specific function of these lncRNA.

  10. Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Hedi ePeterson

    2013-10-01

    Full Text Available Pluripotency in human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs is regulated by three transcription factors - OCT3/4, SOX2 and NANOG. To fully exploit the therapeutic potential of these cells it is essential to have a good mechanistic understanding of the maintenance of self-renewal and pluripotency. In this study, we demonstrate a powerful systems biology approach in which we first expand literature-based network encompassing the core regulators of pluripotency by assessing the behaviour of genes targeted by perturbation experiments. We focused our attention on highly regulated genes encoding cell surface and secreted proteins as these can be more easily manipulated by the use of inhibitors or recombinant proteins. Qualitative modeling based on combining boolean networks and in silico perturbation experiments were employed to identify novel pluripotency-regulating genes. We validated Interleukin-11 (IL-11 and demonstrate that this cytokine is a novel pluripotency-associated factor capable of supporting self-renewal in the absence of exogenously added bFGF in culture. To date, the various protocols for hESCs maintenance require supplementation with bFGF to activate the Activin/Nodal branch of the TGFβ signaling pathway. Additional evidence supporting our findings is that IL-11 belongs to the same protein family as LIF, which is known to be necessary for maintaining pluripotency in mouse but not in human ESCs. These cytokines operate through the same gp130 receptor which interacts with Janus kinases. Our finding might explain why mESCs are in a more naïve cell state compared to hESCs and how to convert primed hESCs back to the naïve state. Taken together, our integrative modeling approach has identified novel genes as putative candidates to be incorporated into the expansion of the current gene regulatory network responsible for inducing and maintaining pluripotency.

  11. Harmful Algal Bloom-Associated Illnesses in Humans and Dogs Identified Through a Pilot Surveillance System - New York, 2015.

    Science.gov (United States)

    Figgatt, Mary; Hyde, James; Dziewulski, David; Wiegert, Eric; Kishbaugh, Scott; Zelin, Grant; Wilson, Lloyd

    2017-11-03

    Cyanobacteria, also known as blue-green algae, are photosynthetic, aquatic organisms found in fresh, brackish, and marine water around the world (1). Rapid proliferation and accumulation of potentially toxin-producing cyanobacteria characterize one type of harmful algal bloom (HAB). HABs have the potential to cause illness in humans and animals (2,3); however, the epidemiology of these illnesses has not been well characterized. Statewide in 2015, a total of 139 HABs were identified in New York, 97 (70%) of which were confirmed through laboratory analysis; 77 independent beach closures were ordered at 37 beaches on 20 different bodies of water. To better characterize HAB-associated illnesses, during June-September 2015, the New York State Department of Health (NYSDOH) implemented a pilot surveillance system in 16 New York counties. Activities included the collection of data from environmental HAB reports, illness reports, poison control centers, and syndromic surveillance, and increased outreach to the public, health care providers, and veterinarians. During June-September, 51 HAB-associated illnesses were reported, including 35 that met the CDC case definitions*; 32 of the cases occurred in humans and three in dogs. In previous years, New York never had more than 10 HAB-associated illnesses reported statewide. The pilot surveillance results from 16 counties during a 4-month period suggest that HAB-associated illnesses might be more common than previously reported.

  12. A Cost Benefit Analysis Approach to Identify Improvements in Merchant Navy Deck Officers’ HELM (Human Element Leadership and Management Training

    Directory of Open Access Journals (Sweden)

    Farhan Saeed

    2016-12-01

    Full Text Available A review of maritime accidents conducted over the last decade confirms that human error is the main contributing factor in these incidents. Well-developed Non-Technical Skills (NTS can reduce the effects of human error. NTS include both interpersonal and cognitive skills such as situation awareness, teamwork, decision-making, leadership, managerial skills, communication and language skills. In a crisis situation good NTS allow a deck officer to recognise the problem quickly, take action to manage the situation, and utilise the available team members safely and effectively. This paper identifies the importance of NTS training for merchant navy deck officers. It also highlights room for improvement in the existing HELM training. Research has shown that at present the structure of HELM training is not very effective. The other safety critical domains’ efforts into NTS developments are investigated and examples of best practice are adapted into the maritime domain’s NTS training. Suggestions are given for improvements to the HELM course based on proven successful methods in other safety critical domains (aviation and anaesthesia. A subsequent Cost Benefit Analysis for improving deck officers’ NTS is also carried out through the use of Bayesian Networks and Decision Tree Modelling.

  13. A radiolabeled antiglobulin assay to identify human cervical mucus immunoglobulin (Ig) A and IgG antisperm antibodies

    International Nuclear Information System (INIS)

    Haas, G.G. Jr.; D'Cruz, O.J.

    1989-01-01

    Antisperm immunoglobulin (Ig) A and IgG antibodies in human cervical mucus (CM) were identified by a radiolabeled antiglobulin assay. Cervical mucus samples from fertile and infertile women were exposed to a 1:3,200 dilution of 2-mercaptoethanol (2-ME), and 5 micrograms of the solubilized CM protein were assayed for the presence of IgA and IgG antisperm and anti-Candida activity by the radiolabeled antiglobulin assay. Purified human secretory IgA and IgG exposed to 2-ME retained the molecular integrity and functional activity of the untreated antibody molecules. CM aliquots collected after high-performance liquid chromatography (HPLC) fractionation were assessed for antisperm antibody activity; antisperm antibody activity was retained in the appropriate IgA or IgG CM fractions. The incidence of CM antisperm antibodies was minimally affected when the radiolabeled antiglobulin assay was performed with a motile sperm population. Approximately 70% of the CM IgA antisperm antibodies were of the IgA1 subclass; CM IgG was primarily of the IgG4 subclass. When Candida antigen was substituted for sperm in the radiolabeled antiglobulin assay, the CM antisperm antibodies were found to be exclusively sperm-specific. These data indicate that the radiolabeled antiglobulin assay using 2-ME to extract CM antibodies is a specific method for the assay of antisperm antibodies in CM

  14. Transcriptome analysis of Neisseria meningitidis in human whole blood and mutagenesis studies identify virulence factors involved in blood survival.

    Directory of Open Access Journals (Sweden)

    Hebert Echenique-Rivera

    2011-05-01

    Full Text Available During infection Neisseria meningitidis (Nm encounters multiple environments within the host, which makes rapid adaptation a crucial factor for meningococcal survival. Despite the importance of invasion into the bloodstream in the meningococcal disease process, little is known about how Nm adapts to permit survival and growth in blood. To address this, we performed a time-course transcriptome analysis using an ex vivo model of human whole blood infection. We observed that Nm alters the expression of ≈30% of ORFs of the genome and major dynamic changes were observed in the expression of transcriptional regulators, transport and binding proteins, energy metabolism, and surface-exposed virulence factors. In particular, we found that the gene encoding the regulator Fur, as well as all genes encoding iron uptake systems, were significantly up-regulated. Analysis of regulated genes encoding for surface-exposed proteins involved in Nm pathogenesis allowed us to better understand mechanisms used to circumvent host defenses. During blood infection, Nm activates genes encoding for the factor H binding proteins, fHbp and NspA, genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as several less characterized surface-exposed proteins that might have a role in blood survival. Through mutagenesis studies of a subset of up-regulated genes we were able to identify new proteins important for survival in human blood and also to identify additional roles of previously known virulence factors in aiding survival in blood. Nm mutant strains lacking the genes encoding the hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate permease LctP were sensitive to killing by human blood. This increased knowledge of how Nm responds to adaptation in blood could also be helpful to develop diagnostic and therapeutic strategies to control the devastating

  15. Epigenetic Library Screen Identifies Abexinostat as Novel Regulator of Adipocytic and Osteoblastic Differentiation of Human Skeletal (Mesenchymal) Stem Cells

    Science.gov (United States)

    Ali, Dalia; Hamam, Rimi; Alfayez, Musaed; Kassem, Moustapha; Aldahmash, Abdullah

    2016-01-01

    The epigenetic mechanisms promoting lineage-specific commitment of human skeletal (mesenchymal or stromal) stem cells (hMSCs) into adipocytes or osteoblasts are still not fully understood. Herein, we performed an epigenetic library functional screen and identified several novel compounds, including abexinostat, which promoted adipocytic and osteoblastic differentiation of hMSCs. Using gene expression microarrays, chromatin immunoprecipitation for H3K9Ac combined with high-throughput DNA sequencing (ChIP-seq), and bioinformatics, we identified several key genes involved in regulating stem cell proliferation and differentiation that were targeted by abexinostat. Concordantly, ChIP-quantitative polymerase chain reaction revealed marked increase in H3K9Ac epigenetic mark on the promoter region of AdipoQ, FABP4, PPARγ, KLF15, CEBPA, SP7, and ALPL in abexinostat-treated hMSCs. Pharmacological inhibition of focal adhesion kinase (PF-573228) or insulin-like growth factor-1R/insulin receptor (NVP-AEW51) signaling exhibited significant inhibition of abexinostat-mediated adipocytic differentiation, whereas inhibition of WNT (XAV939) or transforming growth factor-β (SB505124) signaling abrogated abexinostat-mediated osteogenic differentiation of hMSCs. Our findings provide insight into the understanding of the relationship between the epigenetic effect of histone deacetylase inhibitors, transcription factors, and differentiation pathways governing adipocyte and osteoblast differentiation. Manipulating such pathways allows a novel use for epigenetic compounds in hMSC-based therapies and tissue engineering. Significance This unbiased epigenetic library functional screen identified several novel compounds, including abexinostat, that promoted adipocytic and osteoblastic differentiation of human skeletal (mesenchymal or stromal) stem cells (hMSCs). These data provide new insight into the understanding of the relationship between the epigenetic effect of histone deacetylase

  16. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    International Nuclear Information System (INIS)

    Fischer, L.; Deppert, W.R.; Pfeifer, D.; Stanzel, S.; Weimer, M.; Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P.; Schaefer, W.R.

    2012-01-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  17. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, L.; Deppert, W.R. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Pfeifer, D. [Department of Hematology and Oncology, University Hospital Freiburg (Germany); Stanzel, S.; Weimer, M. [Department of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Schaefer, W.R., E-mail: wolfgang.schaefer@uniklinik-freiburg.de [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)

    2012-05-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  18. Identifying and Measuring the Lifelong Human Capital of “Unskilled” Migrants in the Mexico-US Migratory Circuit

    Directory of Open Access Journals (Sweden)

    Jacqueline Hagan

    2014-05-01

    Full Text Available Most human capital and migration studies classify migrants with limited formal education as “unskilled,” despite substantial skills developed through job and life experiences.  Drawing on a binational multi-stage research project that involved interviews with 320 Mexican migrants and return migrants in North Carolina and Guanajuato, Mexico, we identify the lifelong human capital they acquired and transferred throughout their careers and discover that these include not only basic education and English, but also technical and social skills and competences acquired informally on and off the job throughout the course of one’s life.  We further find that the learning and transfer of skills is a lifelong, gendered process, reflecting the different social contexts and jobs in which men and women learn. In this paper we document several mobility pathways associated with the acquisition and transfer of skills across the migratory circuit, including reskilling, occupational mobility, job jumping, and entrepreneurship.Our study has broad implications for the migration policies of both the US and Mexico.  US immigration policy confers preference to “skilled” immigrants who rank high on traditional human capital characteristics, such as education levels and other formal credentials, but limits the entry of “unskilled” migrants, a categorization that ignores the substantial informal skills they bring to US labor markets.  Instead of focusing only on the continued expansion of immigration policy preferences for narrowly defined skilled migrants, the US government needs to consider more carefully what we mean by skilled workers and design fairer and more effective immigration policies that match their abilities to the specific needs of US industry and thereby recognize the economic contributions of all migrants within a lifelong human capital framework. Mexico can also learn from our findings. Between 2005 and 2010 an estimated 1.4 million

  19. Small molecule screening with laser cytometry can be used to identify pro-survival molecules in human embryonic stem cells.

    Science.gov (United States)

    Sherman, Sean P; Pyle, April D

    2013-01-01

    Differentiated cells from human embryonic stem cells (hESCs) provide an unlimited source of cells for use in regenerative medicine. The recent derivation of human induced pluripotent cells (hiPSCs) provides a potential supply of pluripotent cells that avoid immune rejection and could provide patient-tailored therapy. In addition, the use of pluripotent cells for drug screening could enable routine toxicity testing and evaluation of underlying disease mechanisms. However, prior to establishment of patient specific cells for cell therapy it is important to understand the basic regulation of cell fate decisions in hESCs. One critical issue that hinders the use of these cells is the fact that hESCs survive poorly upon dissociation, which limits genetic manipulation because of poor cloning efficiency of individual hESCs, and hampers production of large-scale culture of hESCs. To address the problems associated with poor growth in culture and our lack of understanding of what regulates hESC signaling, we successfully developed a screening platform that allows for large scale screening for small molecules that regulate survival. In this work we developed the first large scale platform for hESC screening using laser scanning cytometry and were able to validate this platform by identifying the pro-survival molecule HA-1077. These small molecules provide targets for both improving our basic understanding of hESC survival as well as a tool to improve our ability to expand and genetically manipulate hESCs for use in regenerative applications.

  20. Small molecule screening with laser cytometry can be used to identify pro-survival molecules in human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Sean P Sherman

    Full Text Available Differentiated cells from human embryonic stem cells (hESCs provide an unlimited source of cells for use in regenerative medicine. The recent derivation of human induced pluripotent cells (hiPSCs provides a potential supply of pluripotent cells that avoid immune rejection and could provide patient-tailored therapy. In addition, the use of pluripotent cells for drug screening could enable routine toxicity testing and evaluation of underlying disease mechanisms. However, prior to establishment of patient specific cells for cell therapy it is important to understand the basic regulation of cell fate decisions in hESCs. One critical issue that hinders the use of these cells is the fact that hESCs survive poorly upon dissociation, which limits genetic manipulation because of poor cloning efficiency of individual hESCs, and hampers production of large-scale culture of hESCs. To address the problems associated with poor growth in culture and our lack of understanding of what regulates hESC signaling, we successfully developed a screening platform that allows for large scale screening for small molecules that regulate survival. In this work we developed the first large scale platform for hESC screening using laser scanning cytometry and were able to validate this platform by identifying the pro-survival molecule HA-1077. These small molecules provide targets for both improving our basic understanding of hESC survival as well as a tool to improve our ability to expand and genetically manipulate hESCs for use in regenerative applications.

  1. Immunochip analysis identifies novel susceptibility loci in the human leukocyte antigen region for acquired thrombotic thrombocytopenic purpura.

    Science.gov (United States)

    Mancini, I; Ricaño-Ponce, I; Pappalardo, E; Cairo, A; Gorski, M M; Casoli, G; Ferrari, B; Alberti, M; Mikovic, D; Noris, M; Wijmenga, C; Peyvandi, F

    2016-12-01

    Essentials Genetic predisposition to acquired thrombotic thrombocytopenic purpura (aTTP) is mainly unknown. Genetic risk factors for aTTP were studied by Immunochip analysis and replication study. Human leukocyte antigen (HLA) variant rs6903608 conferred a 2.5-fold higher risk of developing aTTP. rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in aTTP. Click to hear Dr Cataland's presentation on acquired thrombotic thrombocytopenic purpura SUMMARY: Background Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor-cleaving protease ADAMTS-13. Similarly to what has been found for other autoimmune disorders, there is evidence of a genetic contribution, including the association of the human leukocyte antigen (HLA) class II complex with disease risk. Objective To identify novel genetic risk factors in acquired TTP. Patients/Methods We undertook a case-control genetic association study in 190 European-origin TTP patients and 1255 Italian healthy controls by using the Illumina Immunochip. Replication analysis in 88 Italian cases and 456 controls was performed with single-nucleotide polymorphism (SNP) TaqMan assays. Results and conclusion We identified one common variant (rs6903608) located within the HLA class II locus that was independently associated with acquired TTP at genome-wide significance and conferred a 2.6-fold increased risk of developing a TTP episode (95% confidence interval [CI] 2.02-3.27, P = 1.64 × 10 -14 ). We also found five non-HLA variants mapping to chromosomes 2, 6, 8 and X that were suggestively associated with the disease: rs9490550, rs115265285, rs5927472, rs7823314, and rs1334768 (nominal P-values ranging from 1.59 × 10 -5 to 7.60 × 10 -5 ). Replication analysis confirmed the association of HLA variant rs6903608 with acquired TTP (pooled P = 3.95 × 10 -19 ). Imputation of classic

  2. Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver.

    Science.gov (United States)

    Papageorgiou, Ioannis; Freytsis, Marina; Court, Michael H

    2016-10-01

    Acetaminophen is the leading cause of acute liver failure (ALF) in many countries including the United States. Hepatic glucuronidation by UDP-glucuronosyltransferase (UGT) 1A subfamily enzymes is the major route of acetaminophen elimination. Reduced glucuronidation may predispose some individuals to acetaminophen-induced ALF, but mechanisms underlying reduced glucuronidation are poorly understood. We hypothesized that specific microRNAs (miRNAs) may reduce UGT1A activity by direct effects on the UGT1A 3'-UTR shared by all UGT1A enzyme transcripts, or by indirect effects on transcription factors regulating UGT1A expression. We performed an unbiased miRNA whole transcriptome association analysis using a bank of human livers with known acetaminophen glucuronidation activities. Of 754 miRNAs evaluated, 9 miRNAs were identified that were significantly overexpressed (p2-fold) in livers with low acetaminophen glucuronidation activities compared with those with high activities. miR-375 showed the highest difference (>10-fold), and was chosen for further mechanistic validation. We demonstrated using in silico analysis and luciferase reporter assays that miR-375 has a unique functional binding site in the 3'-UTR of the aryl hydrocarbon receptor (AhR) gene. Furthermore overexpression of miR-375 in LS180 cells demonstrated significant repression of endogenous AhR protein (by 40%) and mRNA (by 10%), as well as enzyme activity and/or mRNA of AhR regulated enzymes including UGT1A1, UGT1A6, and CYP1A2, without affecting UGT2B7, which is not regulated by AhR. Thus miR-375 is identified as a novel repressor of UGT1A-mediated hepatic acetaminophen glucuronidation through reduced AhR expression, which could predispose some individuals to increased risk for acetaminophen-induced ALF. Published by Elsevier Inc.

  3. Temporal Profiling and Pulsed SILAC Labeling Identify Novel Secreted Proteins During Ex Vivo Osteoblast Differentiation of Human Stromal Stem Cells*

    Science.gov (United States)

    Kristensen, Lars P.; Chen, Li; Nielsen, Maria Overbeck; Qanie, Diyako W.; Kratchmarova, Irina; Kassem, Moustapha; Andersen, Jens S.

    2012-01-01

    It is well established that bone forming cells (osteoblasts) secrete proteins with autocrine, paracrine, and endocrine function. However, the identity and functional role for the majority of these secreted and differentially expressed proteins during the osteoblast (OB) differentiation process, is not fully established. To address these questions, we quantified the temporal dynamics of the human stromal (mesenchymal, skeletal) stem cell (hMSC) secretome during ex vivo OB differentiation using stable isotope labeling by amino acids in cell culture (SILAC). In addition, we employed pulsed SILAC labeling to distinguish genuine secreted proteins from intracellular contaminants. We identified 466 potentially secreted proteins that were quantified at 5 time-points during 14-days ex vivo OB differentiation including 41 proteins known to be involved in OB functions. Among these, 315 proteins exhibited more than 2-fold up or down-regulation. The pulsed SILAC method revealed a strong correlation between the fraction of isotope labeling and the subset of proteins known to be secreted and involved in OB differentiation. We verified SILAC data using qRT-PCR analysis of 9 identified potential novel regulators of OB differentiation. Furthermore, we studied the biological effects of one of these proteins, the hormone stanniocalcin 2 (STC2) and demonstrated its autocrine effects in enhancing osteoblastic differentiation of hMSC. In conclusion, combining complete and pulsed SILAC labeling facilitated the identification of novel factors produced by hMSC with potential role in OB differentiation. Our study demonstrates that the secretome of osteoblastic cells is more complex than previously reported and supports the emerging evidence that osteoblastic cells secrete proteins with endocrine functions and regulate cellular processes beyond bone formation. PMID:22801418

  4. Transcriptome profiling to identify ATRA-responsive genes in human iPSC-derived endoderm for high-throughput point of departure analysis (SOT Annual Meeting)

    Science.gov (United States)

    Toxicological tipping points occur at chemical concentrations that overwhelm a cell’s adaptive response leading to permanent effects. We focused on retinoid signaling in differentiating endoderm to identify developmental pathways for tipping point analysis. Human induced pluripot...

  5. Genomic and transcriptome profiling identified both human and HBV genetic variations and their interactions in Chinese hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Hua Dong

    2015-12-01

    Full Text Available Interaction between HBV and host genome integrations in hepatocellular carcinoma (HCC development is a complex process and the mechanism is still unclear. Here we described in details the quality controls and data mining of aCGH and transcriptome sequencing data on 50 HCC samples from the Chinese patients, published by Dong et al. (2015 (GEO#: GSE65486. In additional to the HBV-MLL4 integration discovered, we also investigated the genetic aberrations of HBV and host genes as well as their genetic interactions. We reported human genome copy number changes and frequent transcriptome variations (e.g. TP53, CTNNB1 mutation, especially MLL family mutations in this cohort of the patients. For HBV genotype C, we identified a novel linkage disequilibrium region covering HBV replication regulatory elements, including basal core promoter, DR1, epsilon and poly-A regions, which is associated with HBV core antigen over-expression and almost exclusive to HBV-MLL4 integration.

  6. Metabolomic approach to human brain spectroscopy identifies associations between clinical features and the frontal lobe metabolome in multiple sclerosis

    Science.gov (United States)

    Vingara, Lisa K.; Yu, Hui Jing; Wagshul, Mark E.; Serafin, Dana; Christodoulou, Christopher; Pelczer, István; Krupp, Lauren B.; Maletić-Savatić, Mirjana

    2013-01-01

    Proton magnetic resonance spectroscopy (1H-MRS) is capable of noninvasively detecting metabolic changes that occur in the brain tissue in vivo. Its clinical utility has been limited so far, however, by analytic methods that focus on independently evaluated metabolites and require prior knowledge about which metabolites to examine. Here, we applied advanced computational methodologies from the field of metabolomics, specifically partial least squares discriminant analysis and orthogonal partial least squares, to in vivo 1H-MRS from frontal lobe white matter of 27 patients with relapsing–remitting multiple sclerosis (RRMS) and 14 healthy controls. We chose RRMS, a chronic demyelinating disorder of the central nervous system, because its complex pathology and variable disease course make the need for reliable biomarkers of disease progression more pressing. We show that in vivo MRS data, when analyzed by multivariate statistical methods, can provide reliable, distinct profiles of MRS-detectable metabolites in different patient populations. Specifically, we find that brain tissue in RRMS patients deviates significantly in its metabolic profile from that of healthy controls, even though it appears normal by standard MRI techniques. We also identify, using statistical means, the metabolic signatures of certain clinical features common in RRMS, such as disability score, cognitive impairments, and response to stress. This approach to human in vivo MRS data should promote understanding of the specific metabolic changes accompanying disease pathogenesis, and could provide biomarkers of disease progression that would be useful in clinical trials. PMID:23751863

  7. Bridging the gap between sample collection and laboratory analysis: using dried blood spots to identify human exposure to chemical agents

    Science.gov (United States)

    Hamelin, Elizabeth I.; Blake, Thomas A.; Perez, Jonas W.; Crow, Brian S.; Shaner, Rebecca L.; Coleman, Rebecca M.; Johnson, Rudolph C.

    2016-05-01

    Public health response to large scale chemical emergencies presents logistical challenges for sample collection, transport, and analysis. Diagnostic methods used to identify and determine exposure to chemical warfare agents, toxins, and poisons traditionally involve blood collection by phlebotomists, cold transport of biomedical samples, and costly sample preparation techniques. Use of dried blood spots, which consist of dried blood on an FDA-approved substrate, can increase analyte stability, decrease infection hazard for those handling samples, greatly reduce the cost of shipping/storing samples by removing the need for refrigeration and cold chain transportation, and be self-prepared by potentially exposed individuals using a simple finger prick and blood spot compatible paper. Our laboratory has developed clinical assays to detect human exposures to nerve agents through the analysis of specific protein adducts and metabolites, for which a simple extraction from a dried blood spot is sufficient for removing matrix interferents and attaining sensitivities on par with traditional sampling methods. The use of dried blood spots can bridge the gap between the laboratory and the field allowing for large scale sample collection with minimal impact on hospital resources while maintaining sensitivity, specificity, traceability, and quality requirements for both clinical and forensic applications.

  8. Molecular analysis of expansion, differentiation, and growth factor treatment of human chondrocytes identifies differentiation markers and growth-related genes.

    Science.gov (United States)

    Benz, Karin; Breit, Stephen; Lukoschek, Martin; Mau, Hans; Richter, Wiltrud

    2002-04-26

    This study is intended to optimise expansion and differentiation of cultured human chondrocytes by growth factor application and to identify molecular markers to monitor their differentiation state. We dissected the molecular consequences of matrix release, monolayer, and 3D-alginate culture, growth factor optimised expansion, and re-differentiation protocols by gene expression analysis. Among 19 common cartilage molecules assessed by cDNA array, six proved best to monitor differentiation. Instant down-regulation at release of cells from the matrix was strongest for COL 2A1, fibromodulin, and PRELP while LUM, CHI3L1, and CHI3L2 were expansion-related. Both gene sets reflected the physiologic effects of the most potent growth-inducing (PDGF-BB) and proteoglycan-inducing (BMP-4) factors. Only CRTAC1 expression correlated with 2D/3D switches while the molecular phenotype of native chondrocytes was not restored. The markers and optimised protocols we suggest can help to improve cell therapy of cartilage defects and chondrocyte differentiation from stem cell sources.

  9. Genome characterization of Turkey Rotavirus G strains from the United States identifies potential recombination events with human Rotavirus B strains.

    Science.gov (United States)

    Chen, Fangzhou; Knutson, Todd P; Porter, Robert E; Ciarlet, Max; Mor, Sunil Kumar; Marthaler, Douglas G

    2017-12-01

    Rotavirus G (RVG) strains have been detected in a variety of avian species, but RVG genomes have been published from only a single pigeon and two chicken strains. Two turkey RVG strains were identified and characterized, one in a hatchery with no reported health issues and the other in a hatchery with high embryo/poult mortality. The two turkey RVG strains shared only an 85.3 % nucleotide sequence identity in the VP7 gene while the other genes possessed high nucleotide identity among them (96.3-99.9 %). Low nucleotide percentage identities (31.6-87.3 %) occurred among the pigeon and chicken RVG strains. Interestingly, potential recombination events were detected between our RVG strains and a human RVB strain, in the VP6 and NSP3 segments. The epidemiology of RVG in avian flocks and the pathogenicity of the two different RVG strains should be further investigated to understand the ecology and impact of RVG in commercial poultry flocks.

  10. A Method to Identify and Isolate Pluripotent Human Stem Cells and Mouse Epiblast Stem Cells Using Lipid Body-Associated Retinyl Ester Fluorescence

    OpenAIRE

    Thangaselvam Muthusamy; Odity Mukherjee; Radhika Menon; Megha Prakash Bangalore; Mitradas M. Panicker

    2014-01-01

    Summary We describe the use of a characteristic blue fluorescence to identify and isolate pluripotent human embryonic stem cells and human-induced pluripotent stem cells. The blue fluorescence emission (450–500 nm) is readily observed by fluorescence microscopy and correlates with the expression of pluripotency markers (OCT4, SOX2, and NANOG). It allows easy identification and isolation of undifferentiated human pluripotent stem cells, high-throughput fluorescence sorting and subsequent propa...

  11. Transcriptomic profiling of curcumin-treated human breast stem cells identifies a role for stearoyl-coa desaturase in breast cancer prevention.

    Science.gov (United States)

    Colacino, Justin A; McDermott, Sean P; Sartor, Maureen A; Wicha, Max S; Rozek, Laura S

    2016-07-01

    Curcumin is a potential agent for both the prevention and treatment of cancers. Curcumin treatment alone, or in combination with piperine, limits breast stem cell self-renewal, while remaining non-toxic to normal differentiated cells. We paired fluorescence-activated cell sorting with RNA sequencing to characterize the genome-wide changes induced specifically in normal breast stem cells following treatment with these compounds. We generated genome-wide maps of the transcriptional changes that occur in epithelial-like (ALDH+) and mesenchymal-like (ALDH-/CD44+/CD24-) normal breast stem/progenitor cells following treatment with curcumin and piperine. We show that curcumin targets both stem cell populations by down-regulating expression of breast stem cell genes including ALDH1A3, CD49f, PROM1, and TP63. We also identified novel genes and pathways targeted by curcumin, including downregulation of SCD. Transient siRNA knockdown of SCD in MCF10A cells significantly inhibited mammosphere formation and the mean proportion of CD44+/CD24- cells, suggesting that SCD is a regulator of breast stemness and a target of curcumin in breast stem cells. These findings extend previous reports of curcumin targeting stem cells, here in two phenotypically distinct stem/progenitor populations isolated from normal human breast tissue. We identified novel mechanisms by which curcumin and piperine target breast stem cell self-renewal, such as by targeting lipid metabolism, providing a mechanistic link between curcumin treatment and stem cell self-renewal. These results elucidate the mechanisms by which curcumin may act as a cancer-preventive compound and provide novel targets for cancer prevention and treatment.

  12. What remains of the Arrow oil?

    International Nuclear Information System (INIS)

    Sergy, G.; Owens, E.

    1993-01-01

    In February 1970, the tanker Arrow became grounded 6.5 km off the north shore of Chedabucto Bay, Nova Scotia, and nearly 72,000 bbl of Bunker C fuel oil were released from the vessel during its subsequent breakup and sinking. The oil was washed ashore in various degrees over an estimated 305 km of the bay's 604-km shoreline, of which only 48 km were cleaned. In addition, the tanker Kurdistan broke in two in pack ice in March 1979 in the Cabot Strait area, spilling ca 54,000 bbl of Bunker C, some of which was later found at 16 locations along the northeast and east shorelines of Chedabucto Bay. In summer 1992, a systematic ground survey of the bay's shorelines was conducted using Environment Canada Shoreline Cleanup Assessment Team (SCAT) procedures. Standard observations were made of oil distribution and width, thickness, and character of the oil residues in 419 coastal segments. Results from the survey are summarized. Oil was found to be present on 13.3 km of the shoreline, with heavy oiling restricted to 1.3 km primarily in the areas of Black Duck Cove and Lennox Passage. Some of this residual oil was identified as coming from the Arrow. Natural weathering processes account for removal of most of the spilled oil from the bay. Oil remaining on the shore was found in areas outside of the zone of physical wave action, in areas of nearshore mixing where fine sediments are not present to weather the oil through biophysical processes, or in crusts formed by oil weathered on the surface. The systematic description of oiled shorelines using the SCAT methodology proved very successful, even for such an old spill. 6 refs

  13. A Genome Wide Association Study (GWAS) from a global cohort identifies common variants in FSHB and SMAD3 driving spontaneous human dizygotic twinning

    NARCIS (Netherlands)

    Aagaard, K.; Mbarek, H.; Steinberg, S.; Nyholt, D.R.; Gordon, S.D.; Miller, M.B.; McRae, A.F.; Hottenga, J.J.; Day, F.R.; Hinds, D.A.; Willemsen, G.; Geus, E.J.C. de; Davies, G.E.; Martin, H.C.; Lambalk, C.B.; Penninx, B.W.J.H.; Jansen, R.; McAloney, K.; Vink, J.M.; Kaprio, J.; Plomin, R.; Spector, T.D.; Magnusson, P.K.E.; Boomsma, D.I.

    2016-01-01

    Objective: Although dizygotic (DZ) twins occur once every 70 live births and has long been suspected to be familial, the genetic loci driving human twinning have not yet been identified. Based on our recent success in identifying "twin genes" in the marmoset primate (which exclusively gestates twins

  14. Identifying the role of human-induced land-use change while assessing drought effects on groundwater recharge

    Science.gov (United States)

    Verbeiren, Boud; Weerasinghe, Imeshi; Vanderhaegen, Sven; Canters, Frank; Uljee, Inge; Engelen, Guy; Jacquemin, Ingrid; Tychon, Bernard; Vangelis, Harris; Tsakiris, George; Batelaan, Okke; Huysmans, Marijke

    2015-04-01

    Drought is mainly regarded as a purely natural phenomenon, driven by the natural variation in precipitation or rather the lack of precipitation. Nowadays many river catchments are, however, altered by human activities having direct effects on the catchment landscape and hydrological response. In case of the occurrence of drought events in those catchments it becomes more complex to determine the effects of drought. To what extent is the hydrological response a direct result of the natural phenomenon and what is the role of the human factor? In this study we focus on the effects of droughts on groundwater recharge. Reliable estimation of groundwater recharge in space and time is of utmost importance for sustainable management of groundwater resources. Groundwater recharge forms the main source for replenishing aquifers. The main factors influencing groundwater recharge are the soil and topographic characteristics, land use and climate. While the first two influencing factors are relatively static, the latter two are (highly) dynamic. Differentiating between the contributions of each of these influencing factors to groundwater recharge is a challenging but important task. On the one hand, the occurrence of meteorological drought events is likely to cause direct, potentially deteriorating, effects on groundwater recharge. On the other hand, this is also the case for on-going land-use dynamics such as extensive urbanisation. The presented methodology aims at distinguishing in space and time between climate (drought-related) and land-use (human-induced) effects, enabling to assess the effects of drought on groundwater recharge. The physically-based water balance model WetSpass is used to calculate groundwater recharge in a distributed way (space and time) for the Dijle-Demer catchments in Belgium. The key issue is to determine land-use dynamics in a consistent way. A land-use timeseries is build based on four base maps. Via a change trajectory analysis the consistency

  15. Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy.

    Science.gov (United States)

    Morales, Eva; Vilahur, Nadia; Salas, Lucas A; Motta, Valeria; Fernandez, Mariana F; Murcia, Mario; Llop, Sabrina; Tardon, Adonina; Fernandez-Tardon, Guillermo; Santa-Marina, Loreto; Gallastegui, Mara; Bollati, Valentina; Estivill, Xavier; Olea, Nicolas; Sunyer, Jordi; Bustamante, Mariona

    2016-10-01

    We conducted an epigenome-wide association study (EWAS) of DNA methylation in placenta in relation to maternal tobacco smoking during pregnancy and examined whether smoking-induced changes lead to low birthweight. DNA methylation in placenta was measured using the Illumina HumanMethylation450 BeadChip in 179 participants from the INfancia y Medio Ambiente (INMA) birth cohort. Methylation levels across 431 311 CpGs were tested for differential methylation between smokers and non-smokers in pregnancy. We took forward three top-ranking loci for further validation and replication by bisulfite pyrosequencing using data of 248 additional participants of the INMA cohort. We examined the association of methylation at smoking-associated loci with birthweight by applying a mediation analysis and a two-sample Mendelian randomization approach. Fifty CpGs were differentially methylated in placenta between smokers and non-smokers during pregnancy [false discovery rate (FDR) < 0.05]. We validated and replicated differential methylation at three top-ranking loci: cg27402634 located between LINC00086 and LEKR1, a gene previously related to birthweight in genome-wide association studies; cg20340720 (WBP1L); and cg25585967 and cg12294026 (TRIO). Dose-response relationships with maternal urine cotinine concentration during pregnancy were confirmed. Differential methylation at cg27402634 explained up to 36% of the lower birthweight in the offspring of smokers (Sobel P-value < 0.05). A two-sample Mendelian randomization analysis provided evidence that decreases in methylation levels at cg27402634 lead to decreases in birthweight. We identified novel loci differentially methylated in placenta in relation to maternal smoking during pregnancy. Adverse effects of maternal smoking on birthweight of the offspring may be mediated by alterations in the placental methylome. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International

  16. Omics analysis of human bone to identify genes and molecular networks regulating skeletal remodeling in health and disease.

    Science.gov (United States)

    Reppe, Sjur; Datta, Harish K; Gautvik, Kaare M

    2017-08-01

    The skeleton is a metabolically active organ throughout life where specific bone cell activity and paracrine/endocrine factors regulate its morphogenesis and remodeling. In recent years, an increasing number of reports have used multi-omics technologies to characterize subsets of bone biological molecular networks. The skeleton is affected by primary and secondary disease, lifestyle and many drugs. Therefore, to obtain relevant and reliable data from well characterized patient and control cohorts are vital. Here we provide a brief overview of omics studies performed on human bone, of which our own studies performed on trans-iliacal bone biopsies from postmenopausal women with osteoporosis (OP) and healthy controls are among the first and largest. Most other studies have been performed on smaller groups of patients, undergoing hip replacement for osteoarthritis (OA) or fracture, and without healthy controls. The major findings emerging from the combined studies are: 1. Unstressed and stressed bone show profoundly different gene expression reflecting differences in bone turnover and remodeling and 2. Omics analyses comparing healthy/OP and control/OA cohorts reveal characteristic changes in transcriptomics, epigenomics (DNA methylation), proteomics and metabolomics. These studies, together with genome-wide association studies, in vitro observations and transgenic animal models have identified a number of genes and gene products that act via Wnt and other signaling systems and are highly associated to bone density and fracture. Future challenge is to understand the functional interactions between bone-related molecular networks and their significance in OP and OA pathogenesis, and also how the genomic architecture is affected in health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Ethnicity and policy concerning the treatment of human remains

    OpenAIRE

    Tamagno, Liliana Ester

    2015-01-01

    El objetivo de este artículo es proyectar reflexiones del campo de la Antropología Social a la discusión sobre el tratamiento de restos humanos de interés arqueológico y bioantropológico. Las mismas son el resultado de una investigación de larga duración fundada en la observación de la dinámica sociocultural actual de los pueblos indígenas, sus presencias, sus demandas, sus saberes, sus utopías. Y, al mismo tiempo, realizada en diálogo con la teoría propia de dicho campo y con los aportes de ...

  18. Returning Home: The Interstate Transportation of Human Remains.

    Science.gov (United States)

    Rowles, Graham D.; Comeaux, Malcolm L.

    1987-01-01

    Many people who die in the United States are transported across state boundaries for burial. Analysis of data from death certificates in 1983 demonstrated 17.1 percent of Arizonans who died were shipped out of state, predominantly back to their state of birth or to their most recent previous residence. (Author/KS)

  19. Human remains found in two wells: a forensic entomology perspective.

    Science.gov (United States)

    Magni, Paola A; Borrini, Matteo; Dadour, Ian R

    2013-09-01

    When estimating the time since death or manner of death, the identification and the pathological evaluations of a body are generally impeded by post mortem changes. Research and case studies help experts to achieve a more accurate diagnosis, but at present there is scant literature covering topics concerning forensic science and decompositional processes in aquatic environments. The two case studies presented each involve a decomposed body found in a unique aquatic environment; namely wells containing ground water. In Case 1 an entomologist attended the scene and in Case 2 an entomologist was only involved after 20 months when it was decided that the insect evidence collected at the second autopsy may be useful in determining a time frame. The first case highlights the problems associated with body retrieval from aquatic environments as the body was removed it dismembered. Fortunately, the well was able to be drained, so much of the insect evidence was retrieved. In the second case the body was found dismembered but the entomological evidence was overlooked and lost. During the second autopsy insects were found, collected, and sent to an entomologist to help clarify the post mortem interval.

  20. Probabilistic analysis showing that a combination of bacteroides and methanobrevibacter source tracking markers is effective for identifying waters contaminated by human fecal pollution

    Science.gov (United States)

    Johnston, Christopher; Byappanahalli, Muruleedhara N.; Gibson, Jacqueline MacDonald; Ufnar, Jennifer A.; Whitman, Richard L.; Stewart, Jill R.

    2013-01-01

    Microbial source tracking assays to identify sources of waterborne contamination typically target genetic markers of host-specific microorganisms. However, no bacterial marker has been shown to be 100% host-specific, and cross-reactivity has been noted in studies evaluating known source samples. Using 485 challenge samples from 20 different human and animal fecal sources, this study evaluated microbial source tracking markers including the Bacteroides HF183 16S rRNA, M. smithii nifH, and Enterococcus esp gene targets that have been proposed as potential indicators of human fecal contamination. Bayes' Theorem was used to calculate the conditional probability that these markers or a combination of markers can correctly identify human sources of fecal pollution. All three human-associated markers were detected in 100% of the sewage samples analyzed. Bacteroides HF183 was the most effective marker for determining whether contamination was specifically from a human source, and greater than 98% certainty that contamination was from a human source was shown when both Bacteroides HF183 and M. smithii nifH markers were present. A high degree of certainty was attained even in cases where the prior probability of human fecal contamination was as low as 8.5%. The combination of Bacteroides HF183 and M. smithii nifH source tracking markers can help identify surface waters impacted by human fecal contamination, information useful for prioritizing restoration activities or assessing health risks from exposure to contaminated waters.

  1. Quality Improvement to Demonstrate the Lack of Reliability of the Human Papillomavirus mRNA Assay to Identify Women With Latent Human Papillomavirus Infections.

    Science.gov (United States)

    Cotton, Sarah; Brown, Robert E; Nugent, Elizabeth K; Robazetti, Sonia C; Berens, Pamela D; Smith, Judith A

    2018-04-01

    To assess the consistency between human papillomavirus (HPV) mRNA testing in women with a history of previous HPV infections diagnosed by HPV DNA assay and the potential effects on follow-up HPV screening. This was a quality improvement study that used data from a pathology laboratory software database reviewed from November 2014 to June 2016 to identify female patients aged 30 years or older with greater than one HPV-positive result, including one or more HPV mRNA assay results and one or more documented HPV DNA assay results for comparison. Previous correlative cytology and colposcopic histopathology were also documented. American College of Obstetricians and Gynecologists' cervical cancer screening guidelines were used to compare potential differences in follow-up recommendations. Four hundred twenty-five charts for female patients 30 years of age or older were identified with one or more prior high-risk HPV infections by DNA assay. There was a 69.3% difference in HPV mRNA results compared with previous HPV DNA-positive results. There was a potential change in follow-up for 71.7% of patients with one prior high-risk-HPV-positive result and 60.0% of patients with two or more prior high-risk HPV-positive results. There were 231 colposcopy reports evaluated in this study. Of these, 62 (26.8%) were abnormal colposcopy reports, including 45 low-grade squamous intraepithelial lesions, 15 high-grade squamous intraepithelial lesions, and two cancers. Twenty-five (40.3%) abnormal colposcopy findings were in patients with a history of at least than two prior HPV DNA-positive results and a report of currently being HPV-negative with the mRNA assay. The HPV mRNA assays are less sensitive for detection of latent HPV infections compared with HPV DNA assays. Based on these data and the potential change in follow-up care, the HPV mRNA assay should not be used for a primary screening tool for cervical cancer. Many pathology laboratories have shifted to using the HPV mRNA assay

  2. Fetal antigen 2: an amniotic protein identified as the aminopropeptide of the alpha 1 chain of human procollagen type I

    DEFF Research Database (Denmark)

    Teisner, B; Rasmussen, H B; Højrup, P

    1992-01-01

    -PAGE analysis gave an M(r) = 27 kDa under reducing and non-reducing conditions for both forms, whereas the exact M(r) determined by mass spectrometry was 14,343 +/- 3 Da. FA2 was N-terminally blocked and after tryptic digestion the amino acid composition and sequences of the peptides showed identity...... with the aminopropeptide of the alpha 1 chain of human procollagen type I as determined by nucleotide sequences. After oxidative procedures normally employed for radio-iodination (iodogen and chloramine-T), FA2 lost its immunoreactivity. An antigen which cross-reacted with polyclonal rabbit anti-human FA2 was demonstrated...... to that of FA2 in human skin. FA2 is a circulating form of the aminopropeptide of the alpha 1 chain of procollagen type I, and this is the first description of its isolation and structural characterization in humans. Udgivelsesdato: 1992-Dec...

  3. Gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for carbon black nanoparticle exposure.

    Science.gov (United States)

    Bourdon, Julie A; Williams, Andrew; Kuo, Byron; Moffat, Ivy; White, Paul A; Halappanavar, Sabina; Vogel, Ulla; Wallin, Håkan; Yauk, Carole L

    2013-01-07

    New approaches are urgently needed to evaluate potential hazards posed by exposure to nanomaterials. Gene expression profiling provides information on potential modes of action and human relevance, and tools have recently become available for pathway-based quantitative risk assessment. The objective of this study was to use toxicogenomics in the context of human health risk assessment. We explore the utility of toxicogenomics in risk assessment, using published gene expression data from C57BL/6 mice exposed to 18, 54 and 162 μg Printex 90 carbon black nanoparticles (CBNP). Analysis of CBNP-perturbed pathways, networks and transcription factors revealed concomitant changes in predicted phenotypes (e.g., pulmonary inflammation and genotoxicity), that correlated with dose and time. Benchmark doses (BMDs) for apical endpoints were comparable to minimum BMDs for relevant pathway-specific expression changes. Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. Very similar fibrotic pathways were perturbed in CBNP-exposed mice and human fibrosis disease models. Our synthesis demonstrates how toxicogenomic profiles may be used in human health risk assessment of nanoparticles and constitutes an important step forward in the ultimate recognition of toxicogenomic endpoints in human health risk. As our knowledge of molecular pathways, dose-response characteristics and relevance to human disease continues to grow, we anticipate that toxicogenomics will become increasingly useful in assessing chemical toxicities and in human health risk assessment. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

  4. Juveniles' Motivations for Remaining in Prostitution

    Science.gov (United States)

    Hwang, Shu-Ling; Bedford, Olwen

    2004-01-01

    Qualitative data from in-depth interviews were collected in 1990-1991, 1992, and 2000 with 49 prostituted juveniles remanded to two rehabilitation centers in Taiwan. These data are analyzed to explore Taiwanese prostituted juveniles' feelings about themselves and their work, their motivations for remaining in prostitution, and their difficulties…

  5. The Annuity Puzzle Remains a Puzzle

    NARCIS (Netherlands)

    Peijnenburg, J.M.J.; Werker, Bas; Nijman, Theo

    We examine incomplete annuity menus and background risk as possible drivers of divergence from full annuitization. Contrary to what is often suggested in the literature, we find that full annuitization remains optimal if saving is possible after retirement. This holds irrespective of whether real or

  6. Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.

    Science.gov (United States)

    Hitomi, Yuki; Tokunaga, Katsushi

    2017-01-01

    Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

  7. ERIC-PCR fingerprinting-based community DNA hybridization to pinpoint genome-specific fragments as molecular markers to identify and track populations common to healthy human guts.

    Science.gov (United States)

    Wei, Guifang; Pan, Li; Du, Huimin; Chen, Junyi; Zhao, Liping

    2004-10-01

    Bacterial populations common to healthy human guts may play important roles in human health. A new strategy for discovering genomic sequences as markers for these bacteria was developed using Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR fingerprinting. Structural features within microbial communities are compared with ERIC-PCR followed by DNA hybridization to identify genomic fragments shared by samples from healthy human individuals. ERIC-PCR profiles of fecal samples from 12 diseased or healthy human and piglet subjects demonstrated stable, unique banding patterns for each individual tested. Sequence homology of DNA fragments in bands of identical size was examined between samples by hybridization under high stringency conditions with DIG-labeled ERIC-PCR products derived from the fecal sample of one healthy child. Comparative analysis of the hybridization profiles with the original agarose fingerprints identified three predominant bands as signatures for populations associated with healthy human guts with sizes of 500, 800 and 1000 bp. Clone library profiling of the three bands produced 17 genome fragments, three of which showed high similarity only with regions of the Bacteroides thetaiotaomicron genome, while the remainder were orphan sequences. Association of these sequences with healthy guts was validated by sequence-selective PCR experiments, which showed that a single fragment was present in all 32 healthy humans and 13 healthy piglets tested. Two fragments were present in the healthy human group and in 18 children with non-infectious diarrhea but not in eight children with infectious diarrhea. Genome fragments identified with this novel strategy may be used as genome-specific markers for dynamic monitoring and sequence-guided isolation of functionally important bacterial populations in complex communities such as human gut microflora.

  8. Novel anti-c-Mpl monoclonal antibodies identified multiple differentially glycosylated human c-Mpl proteins in megakaryocytic cells but not in human solid tumors.

    Science.gov (United States)

    Zhan, Jinghui; Felder, Barbara; Ellison, Aaron R; Winters, Aaron; Salimi-Moosavi, Hossein; Scully, Sheila; Turk, James R; Wei, Ping

    2013-06-01

    Thrombopoietin and its cognate receptor, c-Mpl, are the primary molecular regulators of megakaryocytopoiesis and platelet production. To date the pattern of c-Mpl expression in human solid tumors and the distribution and biochemical properties of c-Mpl proteins in hematopoietic tissues are largely unknown. We have recently developed highly specific mouse monoclonal antibodies (MAb) against human c-Mpl. In this study we used these antibodies to demonstrate the presence of full-length and truncated human c-Mpl proteins in various megakaryocytic cell types, and their absence in over 100 solid tumor cell lines and in the 12 most common primary human tumor types. Quantitative assays showed a cell context-dependent distribution of full-length and truncated c-Mpl proteins. All forms of human c-Mpl protein were found to be modified with extensive N-linked glycosylation but different degrees of sialylation and O-linked glycosylation. Of note, different variants of full-length c-Mpl protein exhibiting differential glycosylation were expressed in erythromegakaryocytic leukemic cell lines and in platelets from healthy human donors. This work provides a comprehensive analysis of human c-Mpl mRNA and protein expression on normal and malignant hematopoietic and non-hematopoietic cells and demonstrates the multiple applications of several novel anti-c-Mpl antibodies.

  9. Proteomic analysis identifies mitochondrial metabolic enzymes as major discriminators between different stages of the failing human myocardium

    DEFF Research Database (Denmark)

    Urbonavicius, Sigitas; Wiggers, Henrik; Bøtker, Hans Erik

    2009-01-01

    Our aim was to identify patterns in differentially regulated proteins associated with the progression of chronic heart failure. We specifically studied proteomics in chronic reversibly (RDM) and irreversibly dysfunctional myocardium (IRDM), as well as end-stage failing myocardium (ESFM).......Our aim was to identify patterns in differentially regulated proteins associated with the progression of chronic heart failure. We specifically studied proteomics in chronic reversibly (RDM) and irreversibly dysfunctional myocardium (IRDM), as well as end-stage failing myocardium (ESFM)....

  10. Identifying Effective Enzyme Activity Targets for Recombinant Class I and Class II Collagenase for Successful Human Islet Isolation

    OpenAIRE

    Balamurugan, Appakalai N.; Green, Michael L.; Breite, Andrew G.; Loganathan, Gopalakrishnan; Wilhelm, Joshua J.; Tweed, Benjamin; Vargova, Lenka; Lockridge, Amber; Kuriti, Manikya; Hughes, Michael G.; Williams, Stuart K.; Hering, Bernhard J.; Dwulet, Francis E.; McCarthy, Robert C.

    2015-01-01

    Isolation following a good manufacturing practice-compliant, human islet product requires development of a robust islet isolation procedure where effective limits of key reagents are known. The enzymes used for islet isolation are critical but little is known about the doses of class I and class II collagenase required for successful islet isolation.

  11. COMPARABLE MEASURES OF COGNITIVE FUNCTION IN HUMAN INFANTS AND LABORATORY ANIMALS TO IDENTIFY ENVIRONMENTAL HEALTH RISKS TO CHILDREN

    Science.gov (United States)

    The importance of including neurodevelopmental end points in environmental studies is clear. A validated measure of cognitive function in human infants that also has a homologous or parallel test in laboratory animal studies will provide a valuable approach for large-scale studie...

  12. HOMOLOGOUS MEASURES OF COGNITIVE FUNCTION IN HUMAN INFANTS AND LABORATORY ANIMALS TO IDENTIFY ENVIRONMENTAL HEALTH RISKS TO CHILDREN

    Science.gov (United States)

    The importance of including neurodevelopmental endpoints in environmental studies is clear. A validated measure of cognitive fucntion in human infants that also has a parallel test in laboratory animal studies will provide a valuable approach for largescale studies. Such a ho...

  13. Meta-Analysis on Blood Transcriptomic Studies Identifies Consistently Co-Expressed PPI Modules as Robust Markers of Human Ageing

    NARCIS (Netherlands)

    van den Akker, E.B.; Passtoors, W.M.; Jansen, R.; van Zwet, E.W.; Goeman, J.J.; Hulsman, M.; Emilsson, V.; Perola, M.; Willemsen, G.; Penninx, B.W.J.H.; Heijmans, B.T.; Maier, A.B.; Boomsma, D.I.; Kok, J.N.; Slagboom, P.E.; Reinders, M.J.T.; Beekman, M.

    2014-01-01

    Summary: The bodily decline that occurs with advancing age strongly impacts on the prospects for future health and life expectancy. Despite the profound role of age in disease etiology, knowledge about the molecular mechanisms driving the process of aging in humans is limited. Here, we used an

  14. A Human Error Analysis Procedure for Identifying Potential Error Modes and Influencing Factors for Test and Maintenance Activities

    International Nuclear Information System (INIS)

    Kim, Jae Whan; Park, Jin Kyun

    2010-01-01

    Periodic or non-periodic test and maintenance (T and M) activities in large, complex systems such as nuclear power plants (NPPs) are essential for sustaining stable and safe operation of the systems. On the other hand, it also has been raised that human erroneous actions that might occur during T and M activities has the possibility of incurring unplanned reactor trips (RTs) or power derate, making safety-related systems unavailable, or making the reliability of components degraded. Contribution of human errors during normal and abnormal activities of NPPs to the unplanned RTs is known to be about 20% of the total events. This paper introduces a procedure for predictively analyzing human error potentials when maintenance personnel perform T and M tasks based on a work procedure or their work plan. This procedure helps plant maintenance team prepare for plausible human errors. The procedure to be introduced is focusing on the recurrent error forms (or modes) in execution-based errors such as wrong object, omission, too little, and wrong action

  15. Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene

    NARCIS (Netherlands)

    Kayser, Manfred; Liu, Fan; Janssens, A. Cecile J. W.; Rivadeneira, Fernando; Lao, Oscar; van Duijn, Kate; Vermeulen, Mark; Arp, Pascal; Jhamai, Mila M.; van Ijcken, Wilfred F. J.; den Dunnen, Johan T.; Heath, Simon; Zelenika, Diana; Despriet, Dominiek D. G.; Klaver, Caroline C. W.; Vingerling, Johannes R.; de Jong, Paulus T. V. M.; Hofman, Albert; Aulchenko, Yurii S.; Uitterlinden, Andre G.; Oostra, Ben A.; van Duijn, Cornelia M.

    2008-01-01

    Human iris color was one of the first traits for which Mendelian segregation was established. To date, the genetics of iris color is still not fully understood and is of interest, particularly in view of forensic applications. In three independent genome-wide association (GWA) studies of a total of

  16. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    Science.gov (United States)

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultur...

  17. Phosphoproteomics identified Endofin, DCBLD2, and KIAA0582 as novel tyrosine phosphorylation targets of EGF signaling and Iressa in human cancer cells

    DEFF Research Database (Denmark)

    Chen, Yunhao; Low, Teck-Yew; Choong, Lee-Yee

    2007-01-01

    With the completion of the human genome project, analysis of enriched phosphotyrosyl proteins from epidermal growth factor (EGF)-induced phosphotyrosine proteome permits the identification of novel downstream substrates of the EGF receptor (EGFR). Using cICAT-based LC-MS/MS method, we identified...

  18. Spatially conserved regulatory elements identified within human and mouse Cd247 gene using high-throughput sequencing data from the ENCODE project

    DEFF Research Database (Denmark)

    Pundhir, Sachin; Hannibal, Tine Dahlbæk; Bang-Berthelsen, Claus Heiner

    2014-01-01

    . In this study, we have utilized the wealth of high-throughput sequencing data produced during the Encyclopedia of DNA Elements (ENCODE) project to identify spatially conserved regulatory elements within the Cd247 gene from human and mouse. We show the presence of two transcription factor binding sites...

  19. Explosives remain preferred methods for platform abandonment

    International Nuclear Information System (INIS)

    Pulsipher, A.; Daniel, W. IV; Kiesler, J.E.; Mackey, V. III

    1996-01-01

    Economics and safety concerns indicate that methods involving explosives remain the most practical and cost-effective means for abandoning oil and gas structures in the Gulf of Mexico. A decade has passed since 51 dead sea turtles, many endangered Kemp's Ridleys, washed ashore on the Texas coast shortly after explosives helped remove several offshore platforms. Although no relationship between the explosions and the dead turtles was ever established, in response to widespread public concern, the US Minerals Management Service (MMS) and National Marine Fisheries Service (NMFS) implemented regulations limiting the size and timing of explosive charges. Also, more importantly, they required that operators pay for observers to survey waters surrounding platforms scheduled for removal for 48 hr before any detonations. If observers spot sea turtles or marine mammals within the danger zone, the platform abandonment is delayed until the turtles leave or are removed. However, concern about the effects of explosives on marine life remains

  20. Combined radiographic and anthropological approaches to victim identification of partially decomposed or skeletal remains

    International Nuclear Information System (INIS)

    Leo, C.; O'Connor, J.E.; McNulty, J.P.

    2013-01-01

    Victim identification is the priority in any scenario involving the discovery of single or multiple human remains for both humanitarian and legal reasons. Such remains may be incomplete and in various stages of decomposition. In such scenarios radiography contributes to both primary and secondary methods of identification; the comparison of ante-mortem dental radiographs to post-mortem findings is a primary identification method whereas the analysis of post-mortem skeletal radiographs to help create a biological profile and identify other individuating features is a secondary method of identification. This review will introduce and explore aspects of victim identification with a focus on the anthropological and radiography-based virtual anthropology approaches to establishing a biological profile, identifying other individuating factors and ultimately restoring an individual's identity. It will highlight the potential contribution that radiography, and radiographers, can make to the identification process and contribute to increasing awareness amongst radiographers of the value of their professional role in such investigations

  1. Mass spectrometry profiling of oxysterols in human sperm identifies 25-hydroxycholesterol as a marker of sperm function

    Directory of Open Access Journals (Sweden)

    Chiara Zerbinati

    2017-04-01

    Full Text Available Cholesterol is a main lipid component of sperm cell that is essential for sperm membrane fluidity, capacitation, and acrosomal reaction. Recent data obtained in bovine sperm showed that sperm capacitation is associated to the formation of oxysterols, oxidized products of cholesterol. The aim of this study was to profile oxysterol content in human semen, and to investigate their potential role in sperm pathophysiology. Among the 12 oxysterols analyzed, 25-hydroxycholesterol (25-HC resulted the most represented in normozoospermic samples, and its concentration positively correlated with spermatozoa number. We detected Cholesterol 25-hydroxylase, the enzyme responsible for 25-HC production, in human spermatozoa at the level of the neck and the post acrosomal area. Upon incubation with spermatozoa, 25-HC induced calcium and cholesterol transients in connection with the acrosomal reaction. Our results support a role for 25-HC in sperm function.

  2. Partial digestion with restriction enzymes of ultraviolet-irradiated human genomic DNA: a method for identifying restriction site polymorphisms

    International Nuclear Information System (INIS)

    Nobile, C.; Romeo, G.

    1988-01-01

    A method for partial digestion of total human DNA with restriction enzymes has been developed on the basis of a principle already utilized by P.A. Whittaker and E. Southern for the analysis of phage lambda recombinants. Total human DNA irradiated with uv light of 254 nm is partially digested by restriction enzymes that recognize sequences containing adjacent thymidines because of TT dimer formation. The products resulting from partial digestion of specific genomic regions are detected in Southern blots by genomic-unique DNA probes with high reproducibility. This procedure is rapid and simple to perform because the same conditions of uv irradiation are used for different enzymes and probes. It is shown that restriction site polymorphisms occurring in the genomic regions analyzed are recognized by the allelic partial digest patterns they determine

  3. Survey of innate immune responses to Burkholderia pseudomallei in human blood identifies a central role for lipopolysaccharide.

    Directory of Open Access Journals (Sweden)

    Narisara Chantratita

    Full Text Available B. pseudomallei is a gram-negative bacterium that causes the tropical infection melioidosis. In northeast Thailand, mortality from melioidosis approaches 40%. As exemplified by the lipopolysaccharide-Toll-like receptor 4 interaction, innate immune responses to invading bacteria are precipitated by activation of host pathogen recognition receptors by pathogen associated molecular patterns. Human melioidosis is characterized by up-regulation of pathogen recognition receptors and pro-inflammatory cytokine release. In contrast to many gram-negative pathogens, however, the lipopolysaccharide of B. pseudomallei is considered only weakly inflammatory. We conducted a study in 300 healthy Thai subjects to investigate the ex vivo human blood response to various bacterial pathogen associated molecular patterns, including lipopolysaccharide from several bacteria, and to two heat-killed B. pseudomallei isolates. We measured cytokine levels after stimulation of fresh whole blood with a panel of stimuli. We found that age, sex, and white blood cell count modulate the innate immune response to B. pseudomallei. We further observed that, in comparison to other stimuli, the innate immune response to B. pseudomallei is most highly correlated with the response to lipopolysaccharide. The magnitude of cytokine responses induced by B. pseudomallei lipopolysaccharide was significantly greater than those induced by lipopolysaccharide from Escherichia coli and comparable to many responses induced by lipopolysaccharide from Salmonella minnesota despite lower amounts of lipid A in the B. pseudomallei lipopolysaccharide preparation. In human monocytes stimulated with B. pseudomallei, addition of polymyxin B or a TLR4/MD-2 neutralizing antibody inhibited the majority of TNF-α production. Challenging existing views, our data indicate that the innate immune response to B. pseudomallei in human blood is largely driven by lipopolysaccharide, and that the response to B

  4. Comparative two-dimensional gel analysis and microsequencing identifies gelsolin as one of the most prominent downregulated markers of transformed human fibroblast and epithelial cells

    DEFF Research Database (Denmark)

    Vandekerckhove, J; Bauw, G; Vancompernolle, K

    1990-01-01

    A systematic comparison of the protein synthesis patterns of cultured normal and transformed human fibroblasts and epithelial cells, using two-dimensional gel protein analysis combined with computerized imaging and data acquisition, identified a 90-kD protein (SSP 5714) as one of the most striking...... downregulated markers typical of the transformed state. Using the information stored in the comprehensive human cellular protein database, we found this protein strongly expressed in several fetal tissues and one of them, epidermis, served as a source for preparative two-dimensional gel electrophoresis. Partial...... and by coelectrophoresis with purified human gelsolin. These results suggest that an important regulatory protein of the microfilament system may play a role in defining the phenotype of transformed human fibroblast and epithelial cells in culture. Udgivelsesdato: 1990-Jul...

  5. Comparative two-dimensional gel analysis and microsequencing identifies gelsolin as one of the most prominent downregulated markers of transformed human fibroblast and epithelial cells

    DEFF Research Database (Denmark)

    Vandekerckhove, J; Bauw, G; Vancompernolle, K

    1990-01-01

    downregulated markers typical of the transformed state. Using the information stored in the comprehensive human cellular protein database, we found this protein strongly expressed in several fetal tissues and one of them, epidermis, served as a source for preparative two-dimensional gel electrophoresis. Partial......A systematic comparison of the protein synthesis patterns of cultured normal and transformed human fibroblasts and epithelial cells, using two-dimensional gel protein analysis combined with computerized imaging and data acquisition, identified a 90-kD protein (SSP 5714) as one of the most striking...... and by coelectrophoresis with purified human gelsolin. These results suggest that an important regulatory protein of the microfilament system may play a role in defining the phenotype of transformed human fibroblast and epithelial cells in culture. Udgivelsesdato: 1990-Jul...

  6. Native human autoantibodies targeting GIPC1 identify differential expression in malignant tumors of the breast and ovary

    International Nuclear Information System (INIS)

    Yavelsky, Victoria; Chan, Gerald; Kalantarov, Gavreel; Trakht, Ilya; Lobel, Leslie; Rohkin, Sarit; Shaco-Levy, Ruthy; Tzikinovsky, Alina; Amir, Tamar; Kohn, Hila; Delgado, Berta; Rabinovich, Alex; Piura, Benjamin

    2008-01-01

    We have been studying the native humoral immune response to cancer and have isolated a library of fully human autoantibodies to a variety of malignancies. We previously described the isolation and characterization of two fully human monoclonal antibodies, 27.F7 and 27.B1, from breast cancer patients that target the protein known as GIPC1, an accessory PDZ-domain binding protein involved in regulation of G-protein signaling. Human monoclonal antibodies, 27.F7 and 27.B1, to GIPC1 demonstrate specific binding to malignant breast cancer tissue with no reactivity with normal breast tissue. The current study employs cELISA, flow cytometry, Western blot analysis as well as immunocytochemistry, and immunohistochemistry. Data is analyzed statistically with the Fisher one-tail and two-tail tests for two independent samples. By screening several other cancer cell lines with 27.F7 and 27.B1 we found consistently strong staining of other human cancer cell lines including SKOV-3 (an ovarian cancer cell line). To further clarify the association of GIPC1 with breast and ovarian cancer we carefully studied 27.F7 and 27.B1 using immunocytochemical and immunohistochemical techniques. An immunohistochemical study of normal ovarian tissue, benign, borderline and malignant ovarian serous tumors, and different types of breast cancer revealed high expression of GIPC1 protein in neoplastic cells. Interestingly, antibodies 27.F7 and 27.B1 demonstrate differential staining of borderline ovarian tumors. Examination of different types of breast cancer demonstrates that the level of GIPC1 expression depends on tumor invasiveness and displays a higher expression than in benign tumors. The present pilot study demonstrates that the GIPC1 protein is overexpressed in ovarian and breast cancer, which may provide an important diagnostic and prognostic marker and will constitute the basis for further study of the role that this protein plays in malignant diseases. In addition, this study suggests that

  7. Comparative proteomics as a tool for identifying specific alterations within interferon response pathways in human glioblastoma multiforme cells

    DEFF Research Database (Denmark)

    Tarasova, Irina A; Tereshkova, Alesya V; Lobas, Anna A

    2018-01-01

    An acquisition of increased sensitivity of cancer cells to viruses is a common outcome of malignant progression that justifies the development of oncolytic viruses as anticancer therapeutics. Studying molecular changes that underlie the sensitivity to viruses would help to identify cases where on...

  8. Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants

    DEFF Research Database (Denmark)

    Li, Yingrui; Vinckenbosch, Nicolas; Tian, Geng

    2010-01-01

    data, we derived the allele frequency spectrum of cSNPs with a minor allele frequency greater than 0.02. We identified a 1.8-fold excess of deleterious, non-syonomyous cSNPs over synonymous cSNPs in the low-frequency range (minor allele frequencies between 2% and 5%). This excess was more pronounced...

  9. Quality Issues Identified During the Evaluation of Biosimilars by the European Medicines Agency's Committee for Medicinal Products for Human Use.

    Science.gov (United States)

    Cilia, Mark; Ruiz, Sol; Richardson, Peter; Salmonson, Tomas; Serracino-Inglott, Anthony; Wirth, Francesca; Borg, John Joseph

    2018-02-01

    The aim of this study was to identify trends in deficiencies raised during the EU evaluation of the quality part of dossiers for marketing authorisation applications of biosimilar medicinal products. All adopted day 120 list of questions on the quality module of 22 marketing authorisation applications for biosimilars submitted to the European Medicines Agency and concluded by the end of October 2015 was analysed. Frequencies of common deficiencies identified were calculated and summarised descriptions included. Frequencies and trends on quality deficiencies were recorded and presented for 22 biosimilar applications. Thirty-two 'major objections' for 9 products were identified from 14 marketing authorisation applications with 15 raised for drug substance and 17 for drug product. In addition, 547 'other concerns' for drug substance and 495 for drug product were also adopted. The frequencies and trends of the identified deficiencies together with their impact were discussed from a regulatory perspective and how these impact key manufacturing processes and key materials used in the production of biosimilars. This study provides an insight to the regulatory challenges prospective companies need to consider when developing biosimilars; it also helps elucidate common pitfalls in the development and production of biosimilars and in the submission of dossiers for their marketing authorisations. The results are expected to be of interest to pharmaceutical companies but also to regulators to obtain consistent information on medicinal products based on transparent rules safeguarding the necessary pharmaceutical quality of medicinal products.

  10. Identifying Effective Enzyme Activity Targets for Recombinant Class I and Class II Collagenase for Successful Human Islet Isolation.

    Science.gov (United States)

    Balamurugan, Appakalai N; Green, Michael L; Breite, Andrew G; Loganathan, Gopalakrishnan; Wilhelm, Joshua J; Tweed, Benjamin; Vargova, Lenka; Lockridge, Amber; Kuriti, Manikya; Hughes, Michael G; Williams, Stuart K; Hering, Bernhard J; Dwulet, Francis E; McCarthy, Robert C

    2016-01-01

    Isolation following a good manufacturing practice-compliant, human islet product requires development of a robust islet isolation procedure where effective limits of key reagents are known. The enzymes used for islet isolation are critical but little is known about the doses of class I and class II collagenase required for successful islet isolation. We used a factorial approach to evaluate the effect of high and low target activities of recombinant class I (rC1) and class II (rC2) collagenase on human islet yield. Consequently, 4 different enzyme formulations with divergent C1:C2 collagenase mass ratios were assessed, each supplemented with the same dose of neutral protease. Both split pancreas and whole pancreas models were used to test enzyme targets (n = 20). Islet yield/g pancreas was compared with historical enzymes (n = 42). Varying the Wunsch (rC2) and collagen degradation activity (CDA, rC1) target dose, and consequently the C1:C2 mass ratio, had no significant effect on tissue digestion. Digestions using higher doses of Wunsch and CDA resulted in comparable islet yields to those obtained with 60% and 50% of those activities, respectively. Factorial analysis revealed no significant main effect of Wunsch activity or CDA for any parameter measured. Aggregate results from 4 different collagenase formulations gave 44% higher islet yield (>5000 islet equivalents/g) in the body/tail of the pancreas (n = 12) when compared with those from the same segment using a standard natural collagenase/protease mixture (n = 6). Additionally, islet yields greater than 5000 islet equivalents/g pancreas were also obtained in whole human pancreas. A broader C1:C2 ratio can be used for human islet isolation than has been used in the past. Recombinant collagenase is an effective replacement for the natural enzyme and we have determined that high islet yield can be obtained even with low doses of rC1:rC2, which is beneficial for the survival of islets.

  11. Identifying and Overcoming Barriers to Effective Consideration of Human and Organisational Factors in Event Analysis and Root Cause Analysis. Workshop Proceedings, September 21-22, 2009, Paris, France

    International Nuclear Information System (INIS)

    2011-01-01

    Nuclear licensees must have effective processes for learning from operating experience in order to manage safety, secure continuous improvement and defend against the potential for repeat events. These processes include root cause analysis (RCA) to identify the underlying causes of events and mechanisms to learn from these analyses and to implement improvements. Correctly identifying and correcting the causes of events will allow lessons to be learned and shared with others in the industry. The treatment of Human and Organisational Factors (HOF) in RCA is of special interest to WGHOF. It is estimated that approximately 60-80% of events in the nuclear industry can be attributed to human and organisational factors. Although the importance of correctly identifying the HOF causes is understood, there is still a tendency for the analysis to focus solely on the technical issues of the event. The history of prominent events across the major hazards sector shows that HOF lessons often fail to be learned. A NEA/CSNI special experts meeting entitled 'Identification of Barriers to Analyzing and Identifying Human and Organisational Factors in Root Cause Analysis' was held at the NEA Headquarters in Paris, France on September 21-22, 2009. A total of 17 participants from 10 countries representing licensee organisations, regulators, international organisations and an independent consultant attended the meeting. The meeting was structured to allow for small group discussions during which a number of themes were explored, followed by plenary discussion. There were also four papers presented which complemented the discussion themes. As set out in the objectives of this work, the participants identified barriers to the effective treatment of HOF in RCA and recommendations to mitigate the effects of these barriers. Many of the barriers and recommendations identified relate to the RCA process in general, not specifically to the treatment of HOF in the RCA process. This is logical, for

  12. Decomposition Technique for Remaining Useful Life Prediction

    Science.gov (United States)

    Saha, Bhaskar (Inventor); Goebel, Kai F. (Inventor); Saxena, Abhinav (Inventor); Celaya, Jose R. (Inventor)

    2014-01-01

    The prognostic tool disclosed here decomposes the problem of estimating the remaining useful life (RUL) of a component or sub-system into two separate regression problems: the feature-to-damage mapping and the operational conditions-to-damage-rate mapping. These maps are initially generated in off-line mode. One or more regression algorithms are used to generate each of these maps from measurements (and features derived from these), operational conditions, and ground truth information. This decomposition technique allows for the explicit quantification and management of different sources of uncertainty present in the process. Next, the maps are used in an on-line mode where run-time data (sensor measurements and operational conditions) are used in conjunction with the maps generated in off-line mode to estimate both current damage state as well as future damage accumulation. Remaining life is computed by subtracting the instance when the extrapolated damage reaches the failure threshold from the instance when the prediction is made.

  13. Industry remains stuck in a transitional mode

    International Nuclear Information System (INIS)

    Garb, F.A.

    1991-01-01

    The near future for industry remains foggy for several obvious reasons. The shake-up of the Soviet Union and how the pieces will reform remains unclear. How successful efforts are to privatize government oil company operations around the world has yet to be determined. A long sought peace in the Middle East seems to be inching closer, but will this continue? If it does continue, what impact will it have on world energy policy? Will American companies, which are now transferring their attention to foreign E and P, also maintain an interest in domestic activities? Is the U.S. economy really on the upswing? We are told that the worst of the recession is over, but try telling this to thousands of workers in the oil patch who are being released monthly by the big players in domestic operations. This paper reports that 1992 should be a better year than 1991, if measured in opportunity. There are more exploration and acquisition options available, both domestically and internationally, than there have been in years. Probably more opportunities exist than there are players-certainly more than can be funded with current financial resources

  14. An Efficient Stepwise Statistical Test to Identify Multiple Linked Human Genetic Variants Associated with Specific Phenotypic Traits.

    Directory of Open Access Journals (Sweden)

    Iksoo Huh

    Full Text Available Recent advances in genotyping methodologies have allowed genome-wide association studies (GWAS to accurately identify genetic variants that associate with common or pathological complex traits. Although most GWAS have focused on associations with single genetic variants, joint identification of multiple genetic variants, and how they interact, is essential for understanding the genetic architecture of complex phenotypic traits. Here, we propose an efficient stepwise method based on the Cochran-Mantel-Haenszel test (for stratified categorical data to identify causal joint multiple genetic variants in GWAS. This method combines the CMH statistic with a stepwise procedure to detect multiple genetic variants associated with specific categorical traits, using a series of associated I × J contingency tables and a null hypothesis of no phenotype association. Through a new stratification scheme based on the sum of minor allele count criteria, we make the method more feasible for GWAS data having sample sizes of several thousands. We also examine the properties of the proposed stepwise method via simulation studies, and show that the stepwise CMH test performs better than other existing methods (e.g., logistic regression and detection of associations by Markov blanket for identifying multiple genetic variants. Finally, we apply the proposed approach to two genomic sequencing datasets to detect linked genetic variants associated with bipolar disorder and obesity, respectively.

  15. Signature pathways identified from gene expression profiles in the human uterine cervix before and after spontaneous term parturition

    Science.gov (United States)

    HASSAN, Sonia S.; ROMERO, Roberto; TARCA, Adi L.; DRAGHICI, Sorin; PINELES, Beth; BUGRIM, Andrej; KHALEK, Nahla; CAMACHO, Natalia; MITTAL, Pooja; YOON, Bo Hyun; ESPINOZA, Jimmy; KIM, Chong Jai; SOROKIN, Yoram; MALONE, John

    2008-01-01

    Objective This study aimed to discover ‘signature pathways’ characterizing biological processes based on genes differentially expressed in the uterine cervix before and after spontaneous labor. Study Design The cervical transcriptome was previously characterized from biopsies taken before and after term labor. Pathway analysis was used to study the differentially expressed genes based on two gene-to-pathway annotation databases (KEGG and Metacore™). Over-represented and highly impacted pathways and connectivity nodes were identified. Results Fifty-two pathways in the Metacore™ database were significantly enriched in differentially expressed genes. Three of the top 5 pathways were known to be involved in cervical remodeling.Two novel pathways were: plasmin signaling and plasminogen activator urokinase (PLAU) signaling. The same analysis in the KEGG database identified 4 significant pathways, of which impact analysis confirmed. Multiple nodes providing connectivity within the plasmin and PLAU signaling pathways were identified.. Conclusions Three strategies for pathway analysis were consistent in their identification of novel, unexpected as well as expected networks, suggesting that this approach is both valid and effective for the elucidation of biological mechanisms involved in cervical dilation and remodeling. PMID:17826407

  16. Identifying a Human Right to Access Sustainable Energy Services in International Human Rights Law (SDG 7)? (LRN Law and Sustainability Conference)

    NARCIS (Netherlands)

    Hesselman, Marlies

    2017-01-01

    This paper assessed whether a right to sustainable energy services access can be found in international human rights law, possibly in support of achieving UN Sustainable Development Goal 7. According to SDG 7.1, States are expected to strive for the implementation of "universal access to modern,

  17. Human health and the water environment: using the DPSEEA framework to identify the driving forces of disease.

    Science.gov (United States)

    Gentry-Shields, Jennifer; Bartram, Jamie

    2014-01-15

    There is a growing awareness of global forces that threaten human health via the water environment. A better understanding of the dynamic between human health and the water environment would enable prediction of the significant driving forces and effective strategies for coping with or preventing them. This report details the use of the Driving Force-Pressure-State-Exposure-Effect-Action (DPSEEA) framework to explore the linkage between water-related diseases and their significant driving forces. The DPSEEA frameworks indicate that a select group of driving forces, including population growth, agriculture, infrastructure (dams and irrigation), and climate change, is at the root cause of key global disease burdens. Construction of the DPSEEA frameworks also allows for the evaluation of public health interventions. Sanitation was found to be a widely applicable and effective intervention, targeting the driver/pressure linkage of most of the water-related diseases examined. Ultimately, the DPSEEA frameworks offer a platform for constituents in both the health and environmental fields to collaborate and commit to a common goal targeting the same driving forces. © 2013.

  18. Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers.

    Science.gov (United States)

    Laíns, Inês; Kelly, Rachel S; Miller, John B; Silva, Rufino; Vavvas, Demetrios G; Kim, Ivana K; Murta, Joaquim N; Lasky-Su, Jessica; Miller, Joan W; Husain, Deeba

    2018-02-01

    To characterize the plasma metabolomic profile of patients with age-related macular degeneration (AMD) using mass spectrometry (MS). Cross-sectional observational study. We prospectively recruited participants with a diagnosis of AMD and a control group (>50 years of age) without any vitreoretinal disease. All participants underwent color fundus photography, used for AMD diagnosis and staging, according to the Age-Related Eye Disease Study classification scheme. Fasting blood samples were collected and plasma was analyzed by Metabolon, Inc. (Durham, NC), using ultrahigh-performance liquid chromatography (UPLC) and high-resolution MS. Metabolon's hardware and software were used to identify peaks and control quality. Principal component analysis and multivariate regression were performed to assess differences in the metabolomic profiles of AMD patients versus controls, while controlling for potential confounders. For biological interpretation, pathway enrichment analysis of significant metabolites was performed using MetaboAnalyst. The primary outcome measures were levels of plasma metabolites in participants with AMD compared with controls and among different AMD severity stages. We included 90 participants with AMD (30 with early AMD, 30 with intermediate AMD, and 30 with late AMD) and 30 controls. Using UPLC and MS, 878 biochemicals were identified. Multivariate logistic regression identified 87 metabolites with levels that differed significantly between AMD patients and controls. Most of these metabolites (82.8%; n = 72), including the most significant metabolites, belonged to the lipid pathways. Analysis of variance revealed that of the 87 metabolites, 48 (55.2%) also were significantly different across the different stages of AMD. A significant enrichment of the glycerophospholipids pathway was identified (P = 4.7 × 10 -9 ) among these metabolites. Participants with AMD have altered plasma metabolomic profiles compared with controls. Our data suggest

  19. New Neanderthal remains from Mani peninsula, Southern Greece: the Kalamakia Middle Paleolithic cave site.

    Science.gov (United States)

    Harvati, Katerina; Darlas, Andreas; Bailey, Shara E; Rein, Thomas R; El Zaatari, Sireen; Fiorenza, Luca; Kullmer, Ottmar; Psathi, Eleni

    2013-06-01

    The Kalamakia cave, a Middle Paleolithic site on the western coast of the Mani peninsula, Greece, was excavated in 1993-2006 by an interdisciplinary team from the Ephoreia of Paleoanthropology and Speleology (Greek Ministry of Culture) and the Muséum national d'Histoire naturelle (Paris). The site is dated to between ca. 100,000 and >39,000 years BP (Before Present) and has yielded Mousterian lithics, a rich fauna, and human remains from several layers. The latter include 10 isolated teeth, a cranial fragment and three postcranial elements. The remains represent at least eight individuals, two of them subadults, and show both carnivore and anthropogenic modifications. They can be identified as Neanderthal on the basis of diagnostic morphology on most specimens. A diet similar to that of Neanderthals from mixed habitat is suggested by our analysis of dental wear (occlusal fingerprint analysis) and microwear (occlusal texture microwear analysis), in agreement with the faunal and palynological analyses of the site. These new fossils significantly expand the Neanderthal sample known from Greece. Together with the human specimens from Lakonis and Apidima, the Kalamakia human remains add to the growing evidence of a strong Neanderthal presence in the Mani region during the Late Pleistocene. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Temporal Profiling and Pulsed SILAC Labeling Identify Novel Secreted Proteins during ex vivo Osteoblast Differentiation of Human Stromal Stem Cells

    DEFF Research Database (Denmark)

    Kristensen, Lars P; Chen, Li; Nielsen, Maria Overbeck

    2012-01-01

    , is not fully established. To address these questions, we quantified the temporal dynamics of the human stromal (mesenchymal, skeletal) stem cell (hMSC) secretome during ex vivo OB differentiation using stable isotope labeling by amino acids in cell culture (SILAC). In addition, we employed pulsed SILAC...... the identification of novel factors produced by hMSC with potential role in OB differentiation. Our study demonstrates that the secretome of osteoblastic cells is more complex than previously reported and supports the emerging evidence that osteoblastic cells secrete proteins with endocrine functions and regulate...... regulators of OB differentiation. Furthermore, we studied the biological effects of one of these proteins, the hormone stanniocalcin 2 (STC2) and demonstrated its autocrine effects in enhancing osteoblastic differentiation of hMSC. In conclusion, combining complete and pulsed SILAC labeling facilitated...

  1. Some remaining problems in HCDA analysis

    International Nuclear Information System (INIS)

    Chang, Y.W.

    1981-01-01

    The safety assessment and licensing of liquid-metal fast breeder reactors (LMFBRs) requires an analysis on the capability of the reactor primary system to sustain the consequences of a hypothetical core-disruptive accident (HCDA). Although computational methods and computer programs developed for HCDA analyses can predict reasonably well the response of the primary containment system, and follow up the phenomena of HCDA from the start of excursion to the time of dynamic equilibrium in the system, there remain areas in the HCDA analysis that merit further analytical and experimental studies. These are the analysis of fluid impact on reactor cover, three-dimensional analysis, the treatment of the perforated plates, material properties under high strain rates and under high temperatures, the treatment of multifield flows, and the treatment of prestressed concrete reactor vessels. The purpose of this paper is to discuss the structural mechanics of HCDA analysis in these areas where improvements are needed

  2. Political, energy events will remain interwoven

    International Nuclear Information System (INIS)

    Jones, D.P.

    1991-01-01

    This paper reports that it is possible to discuss the significance of political and energy events separately, but, in truth, they are intricately interwoven. Furthermore, there are those who will argue that since the two are inseparable, the future is not predictable; so why bother in the endeavor. It is possible that the central point of the exercise may have been missed-yes, the future is unpredictable exclamation point However, the objective of prediction is secondary. The objective of understanding the dynamic forces of change is primary exclamation point With this view of recent history, it is perhaps appropriate to pause and think about the future of the petroleum industry. The future as shaped by political, energy, economic, environmental and technological forces will direct our lives and markets during this decade. Most importantly, what will be the direction that successful businesses take to remain competitive in a global environment? These are interesting issues worthy of provocative thoughts and innovative ideas

  3. Nuclear remains an economic and ecologic asset

    International Nuclear Information System (INIS)

    Le Ngoc, Boris

    2015-01-01

    The author herein outlines the several benefits of nuclear energy and nuclear industry for France. He first outlines that France possesses 97 per cent of de-carbonated electricity thanks to nuclear energy (77 pc) and renewable energies (20 pc, mainly hydraulic), and that renewable energies must be developed in the building and transport sectors to be able to get rid of the environmentally and financially costly fossil energies. He outlines that reactor maintenance and the nuclear fuel cycle industry are fields of technological leadership for the French nuclear industry which is, after motor industry and aircraft industry, the third industrial sector in France. He indicates that nuclear electricity is to remain the most competitive one, and that nuclear energy and renewable energies must not be opposed to it but considered as complementary in the struggle against climate change, i.e. to reduce greenhouse gas emissions and to get rid of the prevalence of fossil energies

  4. Population cycles: generalities, exceptions and remaining mysteries

    Science.gov (United States)

    2018-01-01

    Population cycles are one of nature's great mysteries. For almost a hundred years, innumerable studies have probed the causes of cyclic dynamics in snowshoe hares, voles and lemmings, forest Lepidoptera and grouse. Even though cyclic species have very different life histories, similarities in mechanisms related to their dynamics are apparent. In addition to high reproductive rates and density-related mortality from predators, pathogens or parasitoids, other characteristics include transgenerational reduced reproduction and dispersal with increasing-peak densities, and genetic similarity among populations. Experiments to stop cyclic dynamics and comparisons of cyclic and noncyclic populations provide some understanding but both reproduction and mortality must be considered. What determines variation in amplitude and periodicity of population outbreaks remains a mystery. PMID:29563267

  5. Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence.

    Science.gov (United States)

    Sniekers, Suzanne; Stringer, Sven; Watanabe, Kyoko; Jansen, Philip R; Coleman, Jonathan R I; Krapohl, Eva; Taskesen, Erdogan; Hammerschlag, Anke R; Okbay, Aysu; Zabaneh, Delilah; Amin, Najaf; Breen, Gerome; Cesarini, David; Chabris, Christopher F; Iacono, William G; Ikram, M Arfan; Johannesson, Magnus; Koellinger, Philipp; Lee, James J; Magnusson, Patrik K E; McGue, Matt; Miller, Mike B; Ollier, William E R; Payton, Antony; Pendleton, Neil; Plomin, Robert; Rietveld, Cornelius A; Tiemeier, Henning; van Duijn, Cornelia M; Posthuma, Danielle

    2017-07-01

    Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (r g = 0.89, LD score regression P = 5.4 × 10 -29 ). These findings provide new insight into the genetic architecture of intelligence.

  6. Molecular typing and characterization of a new serotype of human enterovirus (EV-B111) identified in China.

    Science.gov (United States)

    Zhang, Yong; Hong, Mei; Sun, Qiang; Zhu, Shuangli; Tsewang; Li, Xiaolei; Yan, Dongmei; Wang, Dongyan; Xu, Wenbo

    2014-04-01

    Molecular methods, based on sequencing the region encoding the complete VP1 or P1 protein, have enabled the rapid identification of new enterovirus serotypes. In the present study, the complete genome of a newly discovered enterovirus serotype, strain Q0011/XZ/CHN/2000 (hereafter referred to as Q0011), was sequenced and analyzed. The virus, isolated from a stool sample from a patient with acute flaccid paralysis in the Tibet region of China in 2000, was characterized by amplicon sequencing and comparison to a GenBank database of enterovirus nucleotide sequences. The nucleotide sequence encoding the complete VP1 capsid protein is most closely related to the sequences of viruses within the species enterovirus B (EV-B), but is less than 72.1% identical to the homologous sequences of the recognized human enterovirus serotypes, with the greatest homology to EV-B101 and echovirus 32. Moreover, the deduced amino acid sequence of the complete VP1 region is less than 84.7% identical to those of the recognized serotypes, suggesting that the strain is a new serotype of enterovirus within EV-B. The virus was characterized as a new enterovirus type, named EV-B111, by the Picornaviridae Study Group of the International Committee on Taxonomy of Viruses. Low positive rate and titer of neutralizing antibody against EV-B111 were found in the Tibet region of China. Nearly 50% of children ≤5 years had no neutralizing antibody against EV-B111. So the extent of transmission and the exposure of the population to this new EV are very limited. This is the first identification of a new serotype of human enterovirus in China, and strain Q0011 was designated the prototype strain of EV-B111. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Identifying selected regions from heterozygosity and divergence using a light-coverage genomic dataset from two human populations.

    Directory of Open Access Journals (Sweden)

    Taras K Oleksyk

    2008-03-01

    Full Text Available When a selective sweep occurs in the chromosomal region around a target gene in two populations that have recently separated, it produces three dramatic genomic consequences: 1 decreased multi-locus heterozygosity in the region; 2 elevated or diminished genetic divergence (F(ST of multiple polymorphic variants adjacent to the selected locus between the divergent populations, due to the alternative fixation of alleles; and 3 a consequent regional increase in the variance of F(ST (S(2F(ST for the same clustered variants, due to the increased alternative fixation of alleles in the loci surrounding the selection target. In the first part of our study, to search for potential targets of directional selection, we developed and validated a resampling-based computational approach; we then scanned an array of 31 different-sized moving windows of SNP variants (5-65 SNPs across the human genome in a set of European and African American population samples with 183,997 SNP loci after correcting for the recombination rate variation. The analysis revealed 180 regions of recent selection with very strong evidence in either population or both. In the second part of our study, we compared the newly discovered putative regions to those sites previously postulated in the literature, using methods based on inspecting patterns of linkage disequilibrium, population divergence and other methodologies. The newly found regions were cross-validated with those found in nine other studies that have searched for selection signals. Our study was replicated especially well in those regions confirmed by three or more studies. These validated regions were independently verified, using a combination of different methods and different databases in other studies, and should include fewer false positives. The main strength of our analysis method compared to others is that it does not require dense genotyping and therefore can be used with data from population-based genome SNP scans

  8. Does hypertension remain after kidney transplantation?

    Directory of Open Access Journals (Sweden)

    Gholamreza Pourmand

    2015-05-01

    Full Text Available Hypertension is a common complication of kidney transplantation with the prevalence of 80%. Studies in adults have shown a high prevalence of hypertension (HTN in the first three months of transplantation while this rate is reduced to 50- 60% at the end of the first year. HTN remains as a major risk factor for cardiovascular diseases, lower graft survival rates and poor function of transplanted kidney in adults and children. In this retrospective study, medical records of 400 kidney transplantation patients of Sina Hospital were evaluated. Patients were followed monthly for the 1st year, every two months in the 2nd year and every three months after that. In this study 244 (61% patients were male. Mean ± SD age of recipients was 39.3 ± 13.8 years. In most patients (40.8% the cause of end-stage renal disease (ESRD was unknown followed by HTN (26.3%. A total of 166 (41.5% patients had been hypertensive before transplantation and 234 (58.5% had normal blood pressure. Among these 234 individuals, 94 (40.2% developed post-transplantation HTN. On the other hand, among 166 pre-transplant hypertensive patients, 86 patients (56.8% remained hypertensive after transplantation. Totally 180 (45% patients had post-transplantation HTN and 220 patients (55% didn't develop HTN. Based on the findings, the incidence of post-transplantation hypertension is high, and kidney transplantation does not lead to remission of hypertension. On the other hand, hypertension is one of the main causes of ESRD. Thus, early screening of hypertension can prevent kidney damage and reduce further problems in renal transplant recipients.

  9. Kinome expression profiling of human neuroblastoma tumors identifies potential drug targets for ultra high-risk patients.

    Science.gov (United States)

    Russo, Roberta; Cimmino, Flora; Pezone, Lucia; Manna, Francesco; Avitabile, Marianna; Langella, Concetta; Koster, Jan; Casale, Fiorina; Raia, Maddalena; Viola, Giampietro; Fischer, Matthias; Iolascon, Achille; Capasso, Mario

    2017-10-01

    Neuroblastoma (NBL) accounts for >7% of malignancies in patients younger than 15 years. Low- and intermediate-risk patients exhibit excellent or good prognosis after treatment, whereas for high-risk (HR) patients, the estimated 5-year survival rates is still <40%. The ability to stratify HR patients that will not respond to standard treatment strategies is critical for informed treatment decisions. In this study, we have generated a specific kinome gene signature, named Kinome-27, which is able to identify a subset of HR-NBL tumors, named ultra-HR NBL, with highly aggressive clinical behavior that not adequately respond to standard treatments. We have demonstrated that NBL cell lines expressing the same kinome signature of ultra-HR tumors (ultra-HR-like cell lines) may be selectively targeted by the use of two drugs [suberoylanilide hydroxamic acid (SAHA) and Radicicol], and that the synergic combination of these drugs is able to block the ultra-HR-like cells in G2/M phase of cell cycle. The use of our signature in clinical practice will allow identifying patients with negative outcome, which would benefit from new and more personalized treatments. Preclinical in vivo studies are needed to consolidate the SAHA and Radicicol treatment in ultra-HR NBL patients. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. A proteomic study to identify soya allergens--the human response to transgenic versus non-transgenic soya samples.

    Science.gov (United States)

    Batista, Rita; Martins, Isabel; Jeno, Paul; Ricardo, Cândido Pinto; Oliveira, Maria Margarida

    2007-01-01

    In spite of being among the main foods responsible for allergic reactions worldwide, soybean (Glycine max)-derived products continue to be increasingly widespread in a variety of food products due to their well-documented health benefits. Soybean also continues to be one of the elected target crops for genetic modification. The aim of this study was to characterize the soya proteome and, specifically, IgE-reactive proteins as well as to compare the IgE response in soya-allergic individuals to genetically modified Roundup Ready soya versus its non-transgenic control. We performed two-dimensional gel electrophoresis of protein extracts from a 5% genetically modified Roundup Ready flour sample and its non-transgenic control followed by Western blotting with plasma from 5 soya-sensitive individuals. We used peptide tandem mass spectrometry to identify soya proteins (55 protein matches), specifically IgE-binding ones, and to evaluate differences between transgenic and non-transgenic samples. We identified 2 new potential soybean allergens--one is maturation associated and seems to be part of the late embryogenesis abundant proteins group and the other is a cysteine proteinase inhibitor. None of the individuals tested reacted differentially to the transgenic versus non-transgenic samples under study. Soybean endogenous allergen expression does not seem to be altered after genetic modification. Proteomics should be considered a powerful tool for functional characterization of plants and for food safety assessment. Copyright (c) 2007 S. Karger AG, Basel.

  11. Lariat sequencing in a unicellular yeast identifies regulated alternative splicing of exons that are evolutionarily conserved with humans.

    Science.gov (United States)

    Awan, Ali R; Manfredo, Amanda; Pleiss, Jeffrey A

    2013-07-30

    Alternative splicing is a potent regulator of gene expression that vastly increases proteomic diversity in multicellular eukaryotes and is associated with organismal complexity. Although alternative splicing is widespread in vertebrates, little is known about the evolutionary origins of this process, in part because of the absence of phylogenetically conserved events that cross major eukaryotic clades. Here we describe a lariat-sequencing approach, which offers high sensitivity for detecting splicing events, and its application to the unicellular fungus, Schizosaccharomyces pombe, an organism that shares many of the hallmarks of alternative splicing in mammalian systems but for which no previous examples of exon-skipping had been demonstrated. Over 200 previously unannotated splicing events were identified, including examples of regulated alternative splicing. Remarkably, an evolutionary analysis of four of the exons identified here as subject to skipping in S. pombe reveals high sequence conservation and perfect length conservation with their homologs in scores of plants, animals, and fungi. Moreover, alternative splicing of two of these exons have been documented in multiple vertebrate organisms, making these the first demonstrations of identical alternative-splicing patterns in species that are separated by over 1 billion y of evolution.

  12. TRIM28 and β-actin identified via nanobody-based reverse proteomics approach as possible human glioblastoma biomarkers.

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    Ivana Jovčevska

    Full Text Available Malignant gliomas are among the rarest brain tumours, and they have the worst prognosis. Grade IV astrocytoma, known as glioblastoma multiforme (GBM, is a highly lethal disease where the standard therapies of surgery, followed by radiation and chemotherapy, cannot significantly prolong the life expectancy of the patients. Tumour recurrence shows more aggressive form compared to the primary tumour, and results in patient survival from 12 to 15 months only. Although still controversial, the cancer stem cell hypothesis postulates that cancer stem cells are responsible for early relapse of the disease after surgical intervention due to their high resistance to therapy. Alternative strategies for GBM therapy are thus urgently needed. Nanobodies are single-domain antigen-binding fragments of heavy-chain antibodies, and together with classical antibodies, they are part of the camelid immune system. Nanobodies are small and stable, and they share a high degree of sequence identity to the human heavy chain variable domain, and these characteristics offer them advantages over classical antibodies or antibody fragments. We first immunised an alpaca with a human GBM stem-like cell line prepared from primary GBM cultures. Next, a nanobody library was constructed in a phage-display vector. Using nanobody phage-display technology, we selected specific GBM stem-like cell binders through a number of affinity selections, using whole cell protein extracts and membrane protein-enriched extracts from eight different GBM patients, and membrane protein-enriched extracts from two established GBM stem-like cell lines (NCH644 and NCH421K cells. After the enrichment, periplasmic extract ELISA was used to screen for specific clones. These nanobody clones were recloned into the pHEN6 vector, expressed in Escherichia coli WK6, and purified using immobilised metal affinity chromatography and size-exclusion chromatography. Specific nanobody:antigen pairs were obtained and mass

  13. TRIM28 and β-actin identified via nanobody-based reverse proteomics approach as possible human glioblastoma biomarkers.

    Science.gov (United States)

    Jovčevska, Ivana; Zupanec, Neja; Kočevar, Nina; Cesselli, Daniela; Podergajs, Neža; Stokin, Clara Limbaeck; Myers, Michael P; Muyldermans, Serge; Ghassabeh, Gholamreza Hassanzadeh; Motaln, Helena; Ruaro, Maria Elisabetta; Bourkoula, Evgenia; Turnšek, Tamara Lah; Komel, Radovan

    2014-01-01

    Malignant gliomas are among the rarest brain tumours, and they have the worst prognosis. Grade IV astrocytoma, known as glioblastoma multiforme (GBM), is a highly lethal disease where the standard therapies of surgery, followed by radiation and chemotherapy, cannot significantly prolong the life expectancy of the patients. Tumour recurrence shows more aggressive form compared to the primary tumour, and results in patient survival from 12 to 15 months only. Although still controversial, the cancer stem cell hypothesis postulates that cancer stem cells are responsible for early relapse of the disease after surgical intervention due to their high resistance to therapy. Alternative strategies for GBM therapy are thus urgently needed. Nanobodies are single-domain antigen-binding fragments of heavy-chain antibodies, and together with classical antibodies, they are part of the camelid immune system. Nanobodies are small and stable, and they share a high degree of sequence identity to the human heavy chain variable domain, and these characteristics offer them advantages over classical antibodies or antibody fragments. We first immunised an alpaca with a human GBM stem-like cell line prepared from primary GBM cultures. Next, a nanobody library was constructed in a phage-display vector. Using nanobody phage-display technology, we selected specific GBM stem-like cell binders through a number of affinity selections, using whole cell protein extracts and membrane protein-enriched extracts from eight different GBM patients, and membrane protein-enriched extracts from two established GBM stem-like cell lines (NCH644 and NCH421K cells). After the enrichment, periplasmic extract ELISA was used to screen for specific clones. These nanobody clones were recloned into the pHEN6 vector, expressed in Escherichia coli WK6, and purified using immobilised metal affinity chromatography and size-exclusion chromatography. Specific nanobody:antigen pairs were obtained and mass spectrometry

  14. Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Jersie-Christensen, Rosa R; Lyon, David

    2016-01-01

    BACKGROUND: The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients...... with periodontitis and dental caries to healthy individuals. METHODS: Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. The proteins in the saliva samples were subjected to denaturing buffer and digested enzymatically...... and inflammatory markers in periodontitis and dental caries compared to healthy controls. Bacterial proteome profiles and functional annotation were very similar in health and disease. CONCLUSIONS: Overexpression of proteins related to the complement system and inflammation seems to correlate with oral disease...

  15. Combining Phage and Yeast Cell Surface Antibody Display to Identify Novel Cell Type-Selective Internalizing Human Monoclonal Antibodies.

    Science.gov (United States)

    Bidlingmaier, Scott; Su, Yang; Liu, Bin

    2015-01-01

    Using phage antibody display, large libraries can be generated and screened to identify monoclonal antibodies with affinity for target antigens. However, while library size and diversity is an advantage of the phage display method, there is limited ability to quantitatively enrich for specific binding properties such as affinity. One way of overcoming this limitation is to combine the scale of phage display selections with the flexibility and quantitativeness of FACS-based yeast surface display selections. In this chapter we describe protocols for generating yeast surface antibody display libraries using phage antibody display selection outputs as starting material and FACS-based enrichment of target antigen-binding clones from these libraries. These methods should be widely applicable for the identification of monoclonal antibodies with specific binding properties.

  16. Massively parallel signature sequencing and bioinformatics analysis identifies up-regulation of TGFBI and SOX4 in human glioblastoma.

    Directory of Open Access Journals (Sweden)

    Biaoyang Lin

    Full Text Available BACKGROUND: A comprehensive network-based understanding of molecular pathways abnormally altered in glioblastoma multiforme (GBM is essential for developing effective therapeutic approaches for this deadly disease. METHODOLOGY/PRINCIPAL FINDINGS: Applying a next generation sequencing technology, massively parallel signature sequencing (MPSS, we identified a total of 4535 genes that are differentially expressed between normal brain and GBM tissue. The expression changes of three up-regulated genes, CHI3L1, CHI3L2, and FOXM1, and two down-regulated genes, neurogranin and L1CAM, were confirmed by quantitative PCR. Pathway analysis revealed that TGF- beta pathway related genes were significantly up-regulated in GBM tumor samples. An integrative pathway analysis of the TGF beta signaling network identified two alternative TGF-beta signaling pathways mediated by SOX4 (sex determining region Y-box 4 and TGFBI (Transforming growth factor beta induced. Quantitative RT-PCR and immunohistochemistry staining demonstrated that SOX4 and TGFBI expression is elevated in GBM tissues compared with normal brain tissues at both the RNA and protein levels. In vitro functional studies confirmed that TGFBI and SOX4 expression is increased by TGF-beta stimulation and decreased by a specific inhibitor of TGF-beta receptor 1 kinase. CONCLUSIONS/SIGNIFICANCE: Our MPSS database for GBM and normal brain tissues provides a useful resource for the scientific community. The identification of non-SMAD mediated TGF-beta signaling pathways acting through SOX4 and TGFBI (GENE ID:7045 in GBM indicates that these alternative pathways should be considered, in addition to the canonical SMAD mediated pathway, in the development of new therapeutic strategies targeting TGF-beta signaling in GBM. Finally, the construction of an extended TGF-beta signaling network with overlaid gene expression changes between GBM and normal brain extends our understanding of the biology of GBM.

  17. Disease-associated mutations identify a novel region in human STING necessary for the control of type I interferon signaling.

    Science.gov (United States)

    Melki, Isabelle; Rose, Yoann; Uggenti, Carolina; Van Eyck, Lien; Frémond, Marie-Louise; Kitabayashi, Naoki; Rice, Gillian I; Jenkinson, Emma M; Boulai, Anaïs; Jeremiah, Nadia; Gattorno, Marco; Volpi, Sefano; Sacco, Olivero; Terheggen-Lagro, Suzanne W J; Tiddens, Harm A W M; Meyts, Isabelle; Morren, Marie-Anne; De Haes, Petra; Wouters, Carine; Legius, Eric; Corveleyn, Anniek; Rieux-Laucat, Frederic; Bodemer, Christine; Callebaut, Isabelle; Rodero, Mathieu P; Crow, Yanick J

    2017-08-01

    Gain-of-function mutations in transmembrane protein 173 (TMEM173) encoding stimulator of interferon genes (STING) underlie a recently described type I interferonopathy called STING-associated vasculopathy with onset in infancy (SAVI). We sought to define the molecular and cellular pathology relating to 3 individuals variably exhibiting the core features of the SAVI phenotype including systemic inflammation, destructive skin lesions, and interstitial lung disease. Genetic analysis, conformational studies, in vitro assays and ex vivo flow-cytometry were performed. Molecular and in vitro data demonstrate that the pathology in these patients is due to amino acid substitutions at positions 206, 281, and 284 of the human STING protein. These mutations confer cGAMP-independent constitutive activation of type I interferon signaling through TBK1 (TANK-binding kinase), independent from the alternative STING pathway triggered by membrane fusion of enveloped RNA viruses. This constitutive activation was abrogated by ex vivo treatment with the janus kinase 1/2 inhibitor ruxolitinib. Structural analysis indicates that the 3 disease-associated mutations at positions 206, 281, and 284 of the STING protein define a novel cluster of amino acids with functional importance in the regulation of type I interferon signaling. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. A multi-sample based method for identifying common CNVs in normal human genomic structure using high-resolution aCGH data.

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    Chihyun Park

    Full Text Available BACKGROUND: It is difficult to identify copy number variations (CNV in normal human genomic data due to noise and non-linear relationships between different genomic regions and signal intensity. A high-resolution array comparative genomic hybridization (aCGH containing 42 million probes, which is very large compared to previous arrays, was recently published. Most existing CNV detection algorithms do not work well because of noise associated with the large amount of input data and because most of the current methods were not designed to analyze normal human samples. Normal human genome analysis often requires a joint approach across multiple samples. However, the majority of existing methods can only identify CNVs from a single sample. METHODOLOGY AND PRINCIPAL FINDINGS: We developed a multi-sample-based genomic variations detector (MGVD that uses segmentation to identify common breakpoints across multiple samples and a k-means-based clustering strategy. Unlike previous methods, MGVD simultaneously considers multiple samples with different genomic intensities and identifies CNVs and CNV zones (CNVZs; CNVZ is a more precise measure of the location of a genomic variant than the CNV region (CNVR. CONCLUSIONS AND SIGNIFICANCE: We designed a specialized algorithm to detect common CNVs from extremely high-resolution multi-sample aCGH data. MGVD showed high sensitivity and a low false discovery rate for a simulated data set, and outperformed most current methods when real, high-resolution HapMap datasets were analyzed. MGVD also had the fastest runtime compared to the other algorithms evaluated when actual, high-resolution aCGH data were analyzed. The CNVZs identified by MGVD can be used in association studies for revealing relationships between phenotypes and genomic aberrations. Our algorithm was developed with standard C++ and is available in Linux and MS Windows format in the STL library. It is freely available at: http://embio.yonsei.ac.kr/~Park/mgvd.php.

  19. Human Leptospirosis Infection in Fiji: An Eco-epidemiological Approach to Identifying Risk Factors and Environmental Drivers for Transmission.

    Science.gov (United States)

    Lau, Colleen L; Watson, Conall H; Lowry, John H; David, Michael C; Craig, Scott B; Wynwood, Sarah J; Kama, Mike; Nilles, Eric J

    2016-01-01

    Leptospirosis is an important zoonotic disease in the Pacific Islands. In Fiji, two successive cyclones and severe flooding in 2012 resulted in outbreaks with 576 reported cases and 7% case-fatality. We conducted a cross-sectional seroprevalence study and used an eco-epidemiological approach to characterize risk factors and drivers for human leptospirosis infection in Fiji, and aimed to provide an evidence base for improving the effectiveness of public health mitigation and intervention strategies. Antibodies indicative of previous or recent infection were found in 19.4% of 2152 participants (81 communities on the 3 main islands). Questionnaires and geographic information systems data were used to assess variables related to demographics, individual behaviour, contact with animals, socioeconomics, living conditions, land use, and the natural environment. On multivariable logistic regression analysis, variables associated with the presence of Leptospira antibodies included male gender (OR 1.55), iTaukei ethnicity (OR 3.51), living in villages (OR 1.64), lack of treated water at home (OR 1.52), working outdoors (1.64), living in rural areas (OR 1.43), high poverty rate (OR 1.74), living Fiji are complex and multifactorial, with environmental factors playing crucial roles. With global climate change, severe weather events and flooding are expected to intensify in the South Pacific. Population growth could also lead to more intensive livestock farming; and urbanization in developing countries is often associated with urban and peri-urban slums where diseases of poverty proliferate. Climate change, flooding, population growth, urbanization, poverty and agricultural intensification are important drivers of zoonotic disease transmission; these factors may independently, or potentially synergistically, lead to enhanced leptospirosis transmission in Fiji and other similar settings.

  20. Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.

    Directory of Open Access Journals (Sweden)

    Jonathan Göke

    2011-12-01

    Full Text Available Transcription factors are proteins that regulate gene expression by binding to cis-regulatory sequences such as promoters and enhancers. In embryonic stem (ES cells, binding of the transcription factors OCT4, SOX2 and NANOG is essential to maintain the capacity of the cells to differentiate into any cell type of the developing embryo. It is known that transcription factors interact to regulate gene expression. In this study we show that combinatorial binding is strongly associated with co-localization of the transcriptional co-activator Mediator, H3K27ac and increased expression of nearby genes in embryonic stem cells. We observe that the same loci bound by Oct4, Nanog and Sox2 in ES cells frequently drive expression in early embryonic development. Comparison of mouse and human ES cells shows that less than 5% of individual binding events for OCT4, SOX2 and NANOG are shared between species. In contrast, about 15% of combinatorial binding events and even between 53% and 63% of combinatorial binding events at enhancers active in early development are conserved. Our analysis suggests that the combination of OCT4, SOX2 and NANOG binding is critical for transcription in ES cells and likely plays an important role for embryogenesis by binding at conserved early developmental enhancers. Our data suggests that the fast evolutionary rewiring of regulatory networks mainly affects individual binding events, whereas "gene regulatory hotspots" which are bound by multiple factors and active in multiple tissues throughout early development are under stronger evolutionary constraints.

  1. Plasma membrane proteomics of human breast cancer cell lines identifies potential targets for breast cancer diagnosis and treatment.

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    Yvonne S Ziegler

    Full Text Available The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease.

  2. Using Watershed Models and Human Behavioral Analyses to identify Management Options to Reduce Lake Erie's Harmful Algal Blooms

    Science.gov (United States)

    Martin, J.; Wilson, R. S.; Aloysius, N.; Kalcic, M. M.; Roe, B.; Howard, G.; Irwin, E.; Zhang, W.; Liu, H.

    2017-12-01

    In early 2016, the United States and Canada formally agreed to reduce phosphorus inputs to Lake Erie by 40% to reduce the severity of annual Harmful Algal Blooms (HABs). These blooms have become more severe, with record events occurring in 2011 and 2015, and have compromised public safety, shut down drinking water supplies, and negatively impacted the economy of the western Lake Erie basin. Now, a key question is what management options should be pursued to reach the 40% reduction. This presentation will highlight interdisciplinary research to compare the amount and types of practices needed for this reduction to the current and projected levels of adoption. Multiple models of the Maumee watershed identified management plans and adoption rates needed to reach the reduction targets. For example, one successful scenario estimated necessary adoption rates of 50% for subsurface application of fertilizer on row crops, 58% for cover crops, and 78% for buffer strips. Current adoption is below these levels, but future projections based on farmer surveys shows these levels are possible. This information was then used to guide another round of watershed modeling analysis to evaluate scenarios that represented more realistic scenarios based on potential levels of management adoption. In general, these results show that accelerated adoption of management plans is needed compared to past adoption rates, and that some of these greater adoption levels are possible based on likely adoption rates. Increasing the perceived efficacy of the practices is one method that will support greater voluntary rates of adoption.

  3. Ghost Remains After Black Hole Eruption

    Science.gov (United States)

    2009-05-01

    NASA's Chandra X-ray Observatory has found a cosmic "ghost" lurking around a distant supermassive black hole. This is the first detection of such a high-energy apparition, and scientists think it is evidence of a huge eruption produced by the black hole. This discovery presents astronomers with a valuable opportunity to observe phenomena that occurred when the Universe was very young. The X-ray ghost, so-called because a diffuse X-ray source has remained after other radiation from the outburst has died away, is in the Chandra Deep Field-North, one of the deepest X-ray images ever taken. The source, a.k.a. HDF 130, is over 10 billion light years away and existed at a time 3 billion years after the Big Bang, when galaxies and black holes were forming at a high rate. "We'd seen this fuzzy object a few years ago, but didn't realize until now that we were seeing a ghost", said Andy Fabian of the Cambridge University in the United Kingdom. "It's not out there to haunt us, rather it's telling us something - in this case what was happening in this galaxy billions of year ago." Fabian and colleagues think the X-ray glow from HDF 130 is evidence for a powerful outburst from its central black hole in the form of jets of energetic particles traveling at almost the speed of light. When the eruption was ongoing, it produced prodigious amounts of radio and X-radiation, but after several million years, the radio signal faded from view as the electrons radiated away their energy. HDF 130 Chandra X-ray Image of HDF 130 However, less energetic electrons can still produce X-rays by interacting with the pervasive sea of photons remaining from the Big Bang - the cosmic background radiation. Collisions between these electrons and the background photons can impart enough energy to the photons to boost them into the X-ray energy band. This process produces an extended X-ray source that lasts for another 30 million years or so. "This ghost tells us about the black hole's eruption long after

  4. E6 and E7 Gene Polymorphisms in Human Papillomavirus Types-58 and 33 Identified in Southwest China.

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    Zuyi Chen

    Full Text Available Cancer of the cervix is associated with infection by certain types of human papillomavirus (HPV. The gene variants differ in immune responses and oncogenic potential. The E6 and E7 proteins encoded by high-risk HPV play a key role in cellular transformation. HPV-33 and HPV-58 types are highly prevalent among Chinese women. To study the gene intratypic variations, polymorphisms and positive selections of HPV-33 and HPV-58 E6/E7 in southwest China, HPV-33 (E6, E7: n = 216 and HPV-58 (E6, E7: n = 405 E6 and E7 genes were sequenced and compared to others submitted to GenBank. Phylogenetic trees were constructed by Maximum-likelihood and the Kimura 2-parameters methods by MEGA 6 (Molecular Evolutionary Genetics Analysis version 6.0. The diversity of secondary structure was analyzed by PSIPred software. The selection pressures acting on the E6/E7 genes were estimated by PAML 4.8 (Phylogenetic Analyses by Maximun Likelihood version4.8 software. The positive sites of HPV-33 and HPV-58 E6/E7 were contrasted by ClustalX 2.1. Among 216 HPV-33 E6 sequences, 8 single nucleotide mutations were observed with 6/8 non-synonymous and 2/8 synonymous mutations. The 216 HPV-33 E7 sequences showed 3 single nucleotide mutations that were non-synonymous. The 405 HPV-58 E6 sequences revealed 8 single nucleotide mutations with 4/8 non-synonymous and 4/8 synonymous mutations. Among 405 HPV-58 E7 sequences, 13 single nucleotide mutations were observed with 10/13 non-synonymous mutations and 3/13 synonymous mutations. The selective pressure analysis showed that all HPV-33 and 4/6 HPV-58 E6/E7 major non-synonymous mutations were sites of positive selection. All variations were observed in sites belonging to major histocompatibility complex and/or B-cell predicted epitopes. K93N and R145 (I/N were observed in both HPV-33 and HPV-58 E6.

  5. A Sequence in the loop domain of hepatitis C virus E2 protein identified in silico as crucial for the selective binding to human CD81.

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    Chun-Chun Chang

    Full Text Available Hepatitis C virus (HCV is a species-specific pathogenic virus that infects only humans and chimpanzees. Previous studies have indicated that interactions between the HCV E2 protein and CD81 on host cells are required for HCV infection. To determine the crucial factors for species-specific interactions at the molecular level, this study employed in silico molecular docking involving molecular dynamic simulations of the binding of HCV E2 onto human and rat CD81s. In vitro experiments including surface plasmon resonance measurements and cellular binding assays were applied for simple validations of the in silico results. The in silico studies identified two binding regions on the HCV E2 loop domain, namely E2-site1 and E2-site2, as being crucial for the interactions with CD81s, with the E2-site2 as the determinant factor for human-specific binding. Free energy calculations indicated that the E2/CD81 binding process might follow a two-step model involving (i the electrostatic interaction-driven initial binding of human-specific E2-site2, followed by (ii changes in the E2 orientation to facilitate the hydrophobic and van der Waals interaction-driven binding of E2-site1. The sequence of the human-specific, stronger-binding E2-site2 could serve as a candidate template for the future development of HCV-inhibiting peptide drugs.

  6. 16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment.

    Science.gov (United States)

    Guerrero-Preston, Rafael; Godoy-Vitorino, Filipa; Jedlicka, Anne; Rodríguez-Hilario, Arnold; González, Herminio; Bondy, Jessica; Lawson, Fahcina; Folawiyo, Oluwasina; Michailidi, Christina; Dziedzic, Amanda; Thangavel, Rajagowthamee; Hadar, Tal; Noordhuis, Maartje G; Westra, William; Koch, Wayne; Sidransky, David

    2016-08-09

    Systemic inflammatory events and localized disease, mediated by the microbiome, may be measured in saliva as head and neck squamous cell carcinoma (HNSCC) diagnostic and prognostic biomonitors. We used a 16S rRNA V3-V5 marker gene approach to compare the saliva microbiome in DNA isolated from Oropharyngeal (OPSCC), Oral Cavity Squamous Cell Carcinoma (OCSCC) patients and normal epithelium controls, to characterize the HNSCC saliva microbiota and examine their abundance before and after surgical resection.The analyses identified a predominance of Firmicutes, Proteobacteria and Bacteroidetes, with less frequent presence of Actinobacteria and Fusobacteria before surgery. At lower taxonomic levels, the most abundant genera were Streptococcus, Prevotella, Haemophilus, Lactobacillus and Veillonella, with lower numbers of Citrobacter and Neisseraceae genus Kingella. HNSCC patients had a significant loss in richness and diversity of microbiota species (p<0.05) compared to the controls. Overall, the Operational Taxonomic Units network shows that the relative abundance of OTU's within genus Streptococcus, Dialister, and Veillonella can be used to discriminate tumor from control samples (p<0.05). Tumor samples lost Neisseria, Aggregatibacter (Proteobacteria), Haemophillus (Firmicutes) and Leptotrichia (Fusobacteria). Paired taxa within family Enterobacteriaceae, together with genus Oribacterium, distinguish OCSCC samples from OPSCC and normal samples (p<0.05). Similarly, only HPV positive samples have an abundance of genus Gemellaceae and Leuconostoc (p<0.05). Longitudinal analyses of samples taken before and after surgery, revealed a reduction in the alpha diversity measure after surgery, together with an increase of this measure in patients that recurred (p<0.05). These results suggest that microbiota may be used as HNSCC diagnostic and prognostic biomonitors.

  7. Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate.

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    Zena T Wolf

    2015-03-01

    Full Text Available Cleft lip with or without cleft palate (CL/P is the most commonly occurring craniofacial birth defect. We provide insight into the genetic etiology of this birth defect by performing genome-wide association studies in two species: dogs and humans. In the dog, a genome-wide association study of 7 CL/P cases and 112 controls from the Nova Scotia Duck Tolling Retriever (NSDTR breed identified a significantly associated region on canine chromosome 27 (unadjusted p=1.1 x 10(-13; adjusted p= 2.2 x 10(-3. Further analysis in NSDTR families and additional full sibling cases identified a 1.44 Mb homozygous haplotype (chromosome 27: 9.29 - 10.73 Mb segregating with a more complex phenotype of cleft lip, cleft palate, and syndactyly (CLPS in 13 cases. Whole-genome sequencing of 3 CLPS cases and 4 controls at 15X coverage led to the discovery of a frameshift mutation within ADAMTS20 (c.1360_1361delAA (p.Lys453Ilefs*3, which segregated concordant with the phenotype. In a parallel study in humans, a family-based association analysis (DFAM of 125 CL/P cases, 420 unaffected relatives, and 392 controls from a Guatemalan cohort, identified a suggestive association (rs10785430; p =2.67 x 10-6 with the same gene, ADAMTS20. Sequencing of cases from the Guatemalan cohort was unable to identify a causative mutation within the coding region of ADAMTS20, but four coding variants were found in additional cases of CL/P. In summary, this study provides genetic evidence for a role of ADAMTS20 in CL/P development in dogs and as a candidate gene for CL/P development in humans.

  8. Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate.

    Science.gov (United States)

    Wolf, Zena T; Brand, Harrison A; Shaffer, John R; Leslie, Elizabeth J; Arzi, Boaz; Willet, Cali E; Cox, Timothy C; McHenry, Toby; Narayan, Nicole; Feingold, Eleanor; Wang, Xioajing; Sliskovic, Saundra; Karmi, Nili; Safra, Noa; Sanchez, Carla; Deleyiannis, Frederic W B; Murray, Jeffrey C; Wade, Claire M; Marazita, Mary L; Bannasch, Danika L

    2015-03-01

    Cleft lip with or without cleft palate (CL/P) is the most commonly occurring craniofacial birth defect. We provide insight into the genetic etiology of this birth defect by performing genome-wide association studies in two species: dogs and humans. In the dog, a genome-wide association study of 7 CL/P cases and 112 controls from the Nova Scotia Duck Tolling Retriever (NSDTR) breed identified a significantly associated region on canine chromosome 27 (unadjusted p=1.1 x 10(-13); adjusted p= 2.2 x 10(-3)). Further analysis in NSDTR families and additional full sibling cases identified a 1.44 Mb homozygous haplotype (chromosome 27: 9.29 - 10.73 Mb) segregating with a more complex phenotype of cleft lip, cleft palate, and syndactyly (CLPS) in 13 cases. Whole-genome sequencing of 3 CLPS cases and 4 controls at 15X coverage led to the discovery of a frameshift mutation within ADAMTS20 (c.1360_1361delAA (p.Lys453Ilefs*3)), which segregated concordant with the phenotype. In a parallel study in humans, a family-based association analysis (DFAM) of 125 CL/P cases, 420 unaffected relatives, and 392 controls from a Guatemalan cohort, identified a suggestive association (rs10785430; p =2.67 x 10-6) with the same gene, ADAMTS20. Sequencing of cases from the Guatemalan cohort was unable to identify a causative mutation within the coding region of ADAMTS20, but four coding variants were found in additional cases of CL/P. In summary, this study provides genetic evidence for a role of ADAMTS20 in CL/P development in dogs and as a candidate gene for CL/P development in humans.

  9. CD147 (Basigin/Emmprin) identifies FoxP3+CD45RO+CTLA4+-activated human regulatory T cells.

    Science.gov (United States)

    Solstad, Therese; Bains, Simer Jit; Landskron, Johannes; Aandahl, Einar Martin; Thiede, Bernd; Taskén, Kjetil; Torgersen, Knut Martin

    2011-11-10

    Human CD4(+)FoxP3(+) T cells are functionally and phenotypically heterogeneous providing plasticity to immune activation and regulation. To better understand the functional dynamics within this subset, we first used a combined strategy of subcellular fractionation and proteomics to describe differences at the protein level between highly purified human CD4(+)CD25(+) and CD4(+)CD25(-) T-cell populations. This identified a set of membrane proteins highly expressed on the cell surface of human regulatory T cells (Tregs), including CD71, CD95, CD147, and CD148. CD147 (Basigin or Emmprin) divided CD4(+)CD25(+) cells into distinct subsets. Furthermore, CD147, CD25, FoxP3, and in particular CTLA-4 expression correlated. Phenotypical and functional analyses suggested that CD147 marks the switch between resting (CD45RA(+)) and activated (CD45RO(+)) subsets within the FoxP3(+) T-cell population. Sorting of regulatory T cells into CD147(-) and CD147(+) populations demonstrated that CD147 identifies an activated and highly suppressive CD45RO(+) Treg subset. When analyzing CD4(+) T cells for their cytokine producing potential, CD147 levels grouped the FoxP3(+) subset into 3 categories with different ability to produce IL-2, TNF-α, IFN-γ, and IL-17. Together, this suggests that CD147 is a direct marker for activated Tregs within the CD4(+)FoxP3(+) subset and may provide means to manipulate cells important for immune homeostasis.

  10. Remaining Calm in the Midst of Chaos

    International Nuclear Information System (INIS)

    Sullivan, Robin S.; Ryan, Grant W.; Young, Jonathan

    2004-01-01

    At the DOE Hanford site in Washington State, Fluor Hanford, Inc is in the process of developing and, procuring systems to remove and disposition sludge from the 100 Area K Basins. The K Basins were used to store spent fuel from the operating reactors at the Hanford Site. The sludge is a by-product from th corrosion of the fuel and fuel storage canisters. The sludge removal project is very dynamic involving two basins, K East and K West, and has an ambitious schedule for removal and subsequent Basin D and D. The challenge for the safety basis development for this project is how to integrate the analysis with the project schedule and still provide the required project design, development, and regulatory (10CFR830) support. During the development of new project/systems, safety analysis activities are used throughout the design phase to assist in identifying design/safety issues before the design is complete. Control allocation and identification processes assist procurement of equipment during the development phase and a PDSA is required to support the decision to proceed with construction/installation. For the K Basins project, all the safety basis development activities need to be done in the context of new and existing facilities/equipment and an existing safety basis for the K Basins. When schedules are demanding and design, procurement, and safety documentation activities must be completed in parallel, it creates complex issues for maintaining the safety basis current. In addition, developing a safety basis that will cover the lifecycle of the facility creates issues when using it to support the necessary short term decisions at the same time as long term planning. Therefore, it was necessary to develop a safety basis strategy to deal with this situation. This paper discusses the strategy developed to deal with the complexity and project schedule issues and the methods for safety analysis development and documentation being used to assist in maintaining some

  11. Identification of Tenrec ecaudatus, a Wild Mammal Introduced to Mayotte Island, as a Reservoir of the Newly Identified Human Pathogenic Leptospira mayottensis.

    Science.gov (United States)

    Lagadec, Erwan; Gomard, Yann; Le Minter, Gildas; Cordonin, Colette; Cardinale, Eric; Ramasindrazana, Beza; Dietrich, Muriel; Goodman, Steven M; Tortosa, Pablo; Dellagi, Koussay

    2016-08-01

    Leptospirosis is a bacterial zoonosis of major concern on tropical islands. Human populations on western Indian Ocean islands are strongly affected by the disease although each archipelago shows contrasting epidemiology. For instance, Mayotte, part of the Comoros Archipelago, differs from the other neighbouring islands by a high diversity of Leptospira species infecting humans that includes Leptospira mayottensis, a species thought to be unique to this island. Using bacterial culture, molecular detection and typing, the present study explored the wild and domestic local mammalian fauna for renal carriage of leptospires and addressed the genetic relationships of the infecting strains with local isolates obtained from acute human cases and with Leptospira strains hosted by mammal species endemic to nearby Madagascar. Tenrec (Tenrec ecaudatus, Family Tenrecidae), a terrestrial mammal introduced from Madagascar, is identified as a reservoir of L. mayottensis. All isolated L. mayottensis sequence types form a monophyletic clade that includes Leptospira strains infecting humans and tenrecs on Mayotte, as well as two other Malagasy endemic tenrecid species of the genus Microgale. The lower diversity of L. mayottensis in tenrecs from Mayotte, compared to that occurring in Madagascar, suggests that L. mayottensis has indeed a Malagasy origin. This study also showed that introduced rats (Rattus rattus) and dogs are probably the main reservoirs of Leptospira borgpetersenii and Leptospira kirschneri, both bacteria being prevalent in local clinical cases. Data emphasize the epidemiological link between the two neighbouring islands and the role of introduced small mammals in shaping the local epidemiology of leptospirosis.

  12. Identification of Tenrec ecaudatus, a Wild Mammal Introduced to Mayotte Island, as a Reservoir of the Newly Identified Human Pathogenic Leptospira mayottensis.

    Directory of Open Access Journals (Sweden)

    Erwan Lagadec

    2016-08-01

    Full Text Available Leptospirosis is a bacterial zoonosis of major concern on tropical islands. Human populations on western Indian Ocean islands are strongly affected by the disease although each archipelago shows contrasting epidemiology. For instance, Mayotte, part of the Comoros Archipelago, differs from the other neighbouring islands by a high diversity of Leptospira species infecting humans that includes Leptospira mayottensis, a species thought to be unique to this island. Using bacterial culture, molecular detection and typing, the present study explored the wild and domestic local mammalian fauna for renal carriage of leptospires and addressed the genetic relationships of the infecting strains with local isolates obtained from acute human cases and with Leptospira strains hosted by mammal species endemic to nearby Madagascar. Tenrec (Tenrec ecaudatus, Family Tenrecidae, a terrestrial mammal introduced from Madagascar, is identified as a reservoir of L. mayottensis. All isolated L. mayottensis sequence types form a monophyletic clade that includes Leptospira strains infecting humans and tenrecs on Mayotte, as well as two other Malagasy endemic tenrecid species of the genus Microgale. The lower diversity of L. mayottensis in tenrecs from Mayotte, compared to that occurring in Madagascar, suggests that L. mayottensis has indeed a Malagasy origin. This study also showed that introduced rats (Rattus rattus and dogs are probably the main reservoirs of Leptospira borgpetersenii and Leptospira kirschneri, both bacteria being prevalent in local clinical cases. Data emphasize the epidemiological link between the two neighbouring islands and the role of introduced small mammals in shaping the local epidemiology of leptospirosis.

  13. CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells.

    Directory of Open Access Journals (Sweden)

    Rouzbeh Taghizadeh

    2010-12-01

    Full Text Available A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+.We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone.The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.

  14. Development of Human Breast Milk Microbiota-Associated Mice as a Method to Identify Breast Milk Bacteria Capable of Colonizing Gut.

    Science.gov (United States)

    Wang, Xiaoxin; Lu, Huifang; Feng, Zhou; Cao, Jie; Fang, Chao; Xu, Xianming; Zhao, Liping; Shen, Jian

    2017-01-01

    Human breast milk is recognized as one of multiple important sources of commensal bacteria for infant gut. Previous studies searched for the bacterial strains shared between breast milk and infant feces by isolating bacteria and performing strain-level bacterial genotyping, but only limited number of milk bacteria were identified to colonize infant gut, including bacteria from Bifidobacterium , Staphylococcus , Lactobacillus , and Escherichia / Shigella . Here, to identify the breast milk bacteria capable of colonizing gut without the interference of bacteria of origins other than the milk or the necessity to analyze infant feces, normal chow-fed germ-free mice were orally inoculated with the breast milk collected from a mother 2 days after vaginal delivery. According to 16S rRNA gene-based denaturant gradient gel electrophoresis and Illumina sequencing, bacteria at >1% abundance in the milk inoculum were only Streptococcus (56.0%) and Staphylococcus (37.4%), but in the feces of recipient mice were Streptococcus (80.3 ± 2.3%), Corynebacterium (10.0 ± 2.6 %), Staphylococcus (7.6 ± 1.6%), and Propionibacterium (2.1 ± 0.5%) that were previously shown as dominant bacterial genera in the meconium of C-section-delivered human babies; the abundance of anaerobic gut-associated bacteria, Faecalibacterium , Prevotella , Roseburia , Ruminococcus , and Bacteroides , was 0.01-1% in the milk inoculum and 0.003-0.01% in mouse feces; the abundance of Bifidobacterium spp. was below the detection limit of Illumina sequencing in the milk but at 0.003-0.01% in mouse feces. The human breast milk microbiota-associated mouse model may be used to identify additional breast milk bacteria that potentially colonize infant gut.

  15. Encephalitozoon cuniculi in Raw Cow's Milk Remains Infectious After Pasteurization.

    Science.gov (United States)

    Kváč, Martin; Tomanová, Vendula; Samková, Eva; Koubová, Jana; Kotková, Michaela; Hlásková, Lenka; McEvoy, John; Sak, Bohumil

    2016-02-01

    This study describes the prevalence of Encephalitozoon cuniculi in raw cow's milk and evaluates the effect of different milk pasteurization treatments on E. cuniculi infectivity for severe combined immunodeficient (SCID) mice. Using a nested polymerase chain reaction approach, 1 of 50 milking cows was found to repeatedly shed E. cuniculi in its feces and milk. Under experimental conditions, E. cuniculi spores in milk remained infective for SCID mice following pasteurization treatments at 72 °C for 15 s or 85 °C for 5 s. Based on these findings, pasteurized cow's milk should be considered a potential source of E. cuniculi infection in humans.

  16. Oxyntomodulin Identified as a Marker of Type 2 Diabetes and Gastric Bypass Surgery by Mass-spectrometry Based Profiling of Human Plasma

    DEFF Research Database (Denmark)

    Wewer Albrechtsen, Nicolai J; Hornburg, Daniel; Albrechtsen, Reidar

    2016-01-01

    applicability of this platform by studying a hitherto neglected glucose- and appetite-regulating gut hormone, namely, oxyntomodulin. Our results show that the secretion of oxyntomodulin in patients with type 2 diabetes is significantly impaired, and that its level is increased by more than 10-fold after gastric......, oxyntomodulin may participate with GLP-1 in the regulation of glucose metabolism and appetite in humans. In conclusion, this mass spectrometry-based platform is a powerful resource for identifying and characterizing metabolically active low-abundance peptides....

  17. Proteome analysis identifies L1CAM/CD171 and DPP4/CD26 as novel markers of human skin mast cells.

    Science.gov (United States)

    Gschwandtner, M; Paulitschke, V; Mildner, M; Brunner, P M; Hacker, S; Eisenwort, G; Sperr, W R; Valent, P; Gerner, C; Tschachler, E

    2017-01-01

    The function of skin mast cells has been well documented in IgE-mediated allergic reactions, whereas other mast cell functions are poorly defined. This study aimed at identifying novel mast cell proteins by proteome analysis of primary human skin mast cells. The proteome of skin mast cells was compared to other cell types and analyzed using bioinformatics. The expression and function of two proteins hitherto not described in skin mast cells was investigated in isolated mast cells as well as in mast cells in situ. Within the mast cell proteome, we identified 49 highly expressed proteins previously not described in mast cells; 21 of these proteins were found to be selectively expressed in mast cells. Two proteins, the neural cell adhesion molecule L1 and dipeptidyl peptidase 4, were further studied. L1 was found to be highly expressed in mast cells in normal, psoriasis, and mastocytosis skin. Dipeptidyl peptidase 4 was found to be expressed in mast cells in normal, psoriasis, and mastocytosis skin as well as in bone marrow mast cells in patients with systemic mastocytosis. In normal skin, mast cells were identified as a major source of dipeptidyl peptidase 4 and we also found that skin mast cells and fibroblasts secrete an active form of this enzyme. In a systematic proteomics approach we identified two novel mast cell proteins potentially relevant to skin homeostasis: neural cell adhesion molecule L1 and dipeptidyl peptidase 4. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Orthogonal typing methods identify genetic diversity among Belgian Campylobacter jejuni strains isolated over a decade from poultry and cases of sporadic human illness.

    Science.gov (United States)

    Elhadidy, Mohamed; Arguello, Hector; Álvarez-Ordóñez, Avelino; Miller, William G; Duarte, Alexandra; Martiny, Delphine; Hallin, Marie; Vandenberg, Olivier; Dierick, Kate