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Sample records for early-modern human origins

  1. Ancient gene flow from early modern humans into Eastern Neanderthals.

    PubMed

    Kuhlwilm, Martin; Gronau, Ilan; Hubisz, Melissa J; de Filippo, Cesare; Prado-Martinez, Javier; Kircher, Martin; Fu, Qiaomei; Burbano, Hernán A; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Rudan, Pavao; Brajkovic, Dejana; Kucan, Željko; Gušic, Ivan; Marques-Bonet, Tomas; Andrés, Aida M; Viola, Bence; Pääbo, Svante; Meyer, Matthias; Siepel, Adam; Castellano, Sergi

    2016-02-25

    It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000-65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought. PMID:26886800

  2. European early modern humans and the fate of the Neandertals

    PubMed Central

    Trinkaus, Erik

    2007-01-01

    A consideration of the morphological aspects of the earliest modern humans in Europe (more than ≈33,000 B.P.) and the subsequent Gravettian human remains indicates that they possess an anatomical pattern congruent with the autapomorphic (derived) morphology of the earliest (Middle Paleolithic) African modern humans. However, they exhibit a variable suite of features that are either distinctive Neandertal traits and/or plesiomorphic (ancestral) aspects that had been lost among the African Middle Paleolithic modern humans. These features include aspects of neurocranial shape, basicranial external morphology, mandibular ramal and symphyseal form, dental morphology and size, and anteroposterior dental proportions, as well as aspects of the clavicles, scapulae, metacarpals, and appendicular proportions. The ubiquitous and variable presence of these morphological features in the European earlier modern human samples can only be parsimoniously explained as a product of modest levels of assimilation of Neandertals into early modern human populations as the latter dispersed across Europe. This interpretation is in agreement with current analyses of recent and past human molecular data. PMID:17452632

  3. European early modern humans and the fate of the Neandertals.

    PubMed

    Trinkaus, Erik

    2007-05-01

    A consideration of the morphological aspects of the earliest modern humans in Europe (more than approximately 33,000 B.P.) and the subsequent Gravettian human remains indicates that they possess an anatomical pattern congruent with the autapomorphic (derived) morphology of the earliest (Middle Paleolithic) African modern humans. However, they exhibit a variable suite of features that are either distinctive Neandertal traits and/or plesiomorphic (ancestral) aspects that had been lost among the African Middle Paleolithic modern humans. These features include aspects of neurocranial shape, basicranial external morphology, mandibular ramal and symphyseal form, dental morphology and size, and anteroposterior dental proportions, as well as aspects of the clavicles, scapulae, metacarpals, and appendicular proportions. The ubiquitous and variable presence of these morphological features in the European earlier modern human samples can only be parsimoniously explained as a product of modest levels of assimilation of Neandertals into early modern human populations as the latter dispersed across Europe. This interpretation is in agreement with current analyses of recent and past human molecular data. PMID:17452632

  4. Stable isotope dietary analysis of the Tianyuan 1 early modern human

    PubMed Central

    Hu, Yaowu; Shang, Hong; Tong, Haowen; Nehlich, Olaf; Liu, Wu; Zhao, Chaohong; Yu, Jincheng; Wang, Changsui; Trinkaus, Erik; Richards, Michael P.

    2009-01-01

    We report here on the isotopic analysis of the diet of one of the oldest modern humans found in Eurasia, the Tianyuan 1 early modern human dating to ≈40,000 calendar years ago from Tianyuan Cave (Tianyuandong) in the Zhoukoudian region of China. Carbon and nitrogen isotope analysis of the human and associated faunal remains indicate a diet high in animal protein, and the high nitrogen isotope values suggest the consumption of freshwater fish. To confirm this inference, we measured the sulfur isotope values of terrestrial and freshwater animals around the Zhoukoudian area and of the Tianyuan 1 human, which also support the interpretation of a substantial portion of the diet from freshwater fish. This analysis provides the direct evidence for the consumption of aquatic resources by early modern humans in China and has implications for early modern human subsistence and demography. PMID:19581579

  5. Fire as an engineering tool of early modern humans.

    PubMed

    Brown, Kyle S; Marean, Curtis W; Herries, Andy I R; Jacobs, Zenobia; Tribolo, Chantal; Braun, David; Roberts, David L; Meyer, Michael C; Bernatchez, Jocelyn

    2009-08-14

    The controlled use of fire was a breakthrough adaptation in human evolution. It first provided heat and light and later allowed the physical properties of materials to be manipulated for the production of ceramics and metals. The analysis of tools at multiple sites shows that the source stone materials were systematically manipulated with fire to improve their flaking properties. Heat treatment predominates among silcrete tools at approximately 72 thousand years ago (ka) and appears as early as 164 ka at Pinnacle Point, on the south coast of South Africa. Heat treatment demands a sophisticated knowledge of fire and an elevated cognitive ability and appears at roughly the same time as widespread evidence for symbolic behavior. PMID:19679810

  6. Early modern humans and morphological variation in Southeast Asia: fossil evidence from Tam Pa Ling, Laos.

    PubMed

    Demeter, Fabrice; Shackelford, Laura; Westaway, Kira; Duringer, Philippe; Bacon, Anne-Marie; Ponche, Jean-Luc; Wu, Xiujie; Sayavongkhamdy, Thongsa; Zhao, Jian-Xin; Barnes, Lani; Boyon, Marc; Sichanthongtip, Phonephanh; Sénégas, Frank; Karpoff, Anne-Marie; Patole-Edoumba, Elise; Coppens, Yves; Braga, José

    2015-01-01

    Little is known about the timing of modern human emergence and occupation in Eastern Eurasia. However a rapid migration out of Africa into Southeast Asia by at least 60 ka is supported by archaeological, paleogenetic and paleoanthropological data. Recent discoveries in Laos, a modern human cranium (TPL1) from Tam Pa Ling's cave, provided the first evidence for the presence of early modern humans in mainland Southeast Asia by 63-46 ka. In the current study, a complete human mandible representing a second individual, TPL 2, is described using discrete traits and geometric morphometrics with an emphasis on determining its population affinity. The TPL2 mandible has a chin and other discrete traits consistent with early modern humans, but it retains a robust lateral corpus and internal corporal morphology typical of archaic humans across the Old World. The mosaic morphology of TPL2 and the fully modern human morphology of TPL1 suggest that a large range of morphological variation was present in early modern human populations residing in the eastern Eurasia by MIS 3. PMID:25849125

  7. Early Modern Humans and Morphological Variation in Southeast Asia: Fossil Evidence from Tam Pa Ling, Laos

    PubMed Central

    Demeter, Fabrice; Shackelford, Laura; Westaway, Kira; Duringer, Philippe; Bacon, Anne-Marie; Ponche, Jean-Luc; Wu, Xiujie; Sayavongkhamdy, Thongsa; Zhao, Jian-Xin; Barnes, Lani; Boyon, Marc; Sichanthongtip, Phonephanh; Sénégas, Frank; Karpoff, Anne-Marie; Patole-Edoumba, Elise; Coppens, Yves; Braga, José

    2015-01-01

    Little is known about the timing of modern human emergence and occupation in Eastern Eurasia. However a rapid migration out of Africa into Southeast Asia by at least 60 ka is supported by archaeological, paleogenetic and paleoanthropological data. Recent discoveries in Laos, a modern human cranium (TPL1) from Tam Pa Ling‘s cave, provided the first evidence for the presence of early modern humans in mainland Southeast Asia by 63-46 ka. In the current study, a complete human mandible representing a second individual, TPL 2, is described using discrete traits and geometric morphometrics with an emphasis on determining its population affinity. The TPL2 mandible has a chin and other discrete traits consistent with early modern humans, but it retains a robust lateral corpus and internal corporal morphology typical of archaic humans across the Old World. The mosaic morphology of TPL2 and the fully modern human morphology of TPL1 suggest that a large range of morphological variation was present in early modern human populations residing in the eastern Eurasia by MIS 3. PMID:25849125

  8. Isotopic evidence for the diets of European Neanderthals and early modern humans

    PubMed Central

    Richards, Michael P.; Trinkaus, Erik

    2009-01-01

    We report here on the direct isotopic evidence for Neanderthal and early modern human diets in Europe. Isotopic methods indicate the sources of dietary protein over many years of life, and show that Neanderthals had a similar diet through time (≈120,000 to ≈37,000 cal BP) and in different regions of Europe. The isotopic evidence indicates that in all cases Neanderthals were top-level carnivores and obtained all, or most, of their dietary protein from large herbivores. In contrast, early modern humans (≈40,000 to ≈27,000 cal BP) exhibited a wider range of isotopic values, and a number of individuals had evidence for the consumption of aquatic (marine and freshwater) resources. This pattern includes Oase 1, the oldest directly dated modern human in Europe (≈40,000 cal BP) with the highest nitrogen isotope value of all of the humans studied, likely because of freshwater fish consumption. As Oase 1 was close in time to the last Neanderthals, these data may indicate a significant dietary shift associated with the changing population dynamics of modern human emergence in Europe. PMID:19706482

  9. Plant foods and the dietary ecology of Neanderthals and early modern humans.

    PubMed

    Henry, Amanda G; Brooks, Alison S; Piperno, Dolores R

    2014-04-01

    One of the most important challenges in anthropology is understanding the disappearance of Neanderthals. Previous research suggests that Neanderthals had a narrower diet than early modern humans, in part because they lacked various social and technological advances that lead to greater dietary variety, such as a sexual division of labor and the use of complex projectile weapons. The wider diet of early modern humans would have provided more calories and nutrients, increasing fertility, decreasing mortality and supporting large population sizes, allowing them to out-compete Neanderthals. However, this model for Neanderthal dietary behavior is based on analysis of animal remains, stable isotopes, and other methods that provide evidence only of animal food in the diet. This model does not take into account the potential role of plant food. Here we present results from the first broad comparison of plant foods in the diets of Neanderthals and early modern humans from several populations in Europe, the Near East, and Africa. Our data comes from the analysis of plant microremains (starch grains and phytoliths) in dental calculus and on stone tools. Our results suggest that both species consumed a similarly wide array of plant foods, including foods that are often considered low-ranked, like underground storage organs and grass seeds. Plants were consumed across the entire range of individuals and sites we examined, and none of the expected predictors of variation (species, geographic region, or associated stone tool technology) had a strong influence on the number of plant species consumed. Our data suggest that Neanderthal dietary ecology was more complex than previously thought. This implies that the relationship between Neanderthal technology, social behavior, and food acquisition strategies must be better explored. PMID:24612646

  10. Volcanic ash layers illuminate the resilience of Neanderthals and early modern humans to natural hazards

    PubMed Central

    Lowe, John; Barton, Nick; Blockley, Simon; Ramsey, Christopher Bronk; Cullen, Victoria L.; Davies, William; Gamble, Clive; Grant, Katharine; Hardiman, Mark; Housley, Rupert; Lane, Christine S.; Lee, Sharen; Lewis, Mark; MacLeod, Alison; Menzies, Martin; Müller, Wolfgang; Pollard, Mark; Price, Catherine; Roberts, Andrew P.; Rohling, Eelco J.; Satow, Chris; Smith, Victoria C.; Stringer, Chris B.; Tomlinson, Emma L.; White, Dustin; Albert, Paul; Arienzo, Ilenia; Barker, Graeme; Borić, Dušan; Carandente, Antonio; Civetta, Lucia; Ferrier, Catherine; Guadelli, Jean-Luc; Karkanas, Panagiotis; Koumouzelis, Margarita; Müller, Ulrich C.; Orsi, Giovanni; Pross, Jörg; Rosi, Mauro; Shalamanov-Korobar, Ljiljiana; Sirakov, Nikolay; Tzedakis, Polychronis C.

    2012-01-01

    Marked changes in human dispersal and development during the Middle to Upper Paleolithic transition have been attributed to massive volcanic eruption and/or severe climatic deterioration. We test this concept using records of volcanic ash layers of the Campanian Ignimbrite eruption dated to ca. 40,000 y ago (40 ka B.P.). The distribution of the Campanian Ignimbrite has been enhanced by the discovery of cryptotephra deposits (volcanic ash layers that are not visible to the naked eye) in archaeological cave sequences. They enable us to synchronize archaeological and paleoclimatic records through the period of transition from Neanderthal to the earliest anatomically modern human populations in Europe. Our results confirm that the combined effects of a major volcanic eruption and severe climatic cooling failed to have lasting impacts on Neanderthals or early modern humans in Europe. We infer that modern humans proved a greater competitive threat to indigenous populations than natural disasters. PMID:22826222

  11. Behavioral inferences from the Skhul/Qafzeh early modern human hand remains

    PubMed Central

    Niewoehner, Wesley A.

    2001-01-01

    Two groups of humans are found in the Near East ≈100,000 years ago, the late archaic Neanderthals and the early modern Skhul/Qafzeh humans. Observations that Neanderthals were more heavily muscled, had stronger upper-limb bones, and possessed unusual shapes and orientations of some upper-limb joint complexes relative to the Skhul/Qafzeh hominids, have led some researchers to conclude that significant between-group upper-limb-related behavioral differences must have been present, despite the association of the two groups with similar Middle Paleolithic archeological complexes. A three-dimensional morphometric analysis of the hand remains of the Skhul/Qafzeh hominids, Neanderthals, early and late Upper Paleolithic humans, and Holocene humans supports the dichotomy. The Skhul/Qafzeh carpometacarpal remains do not have any unique morphologies relative to the other fossil samples remains examined. However, in the functionally significant metacarpal 1 and 3 bases they resemble Upper Paleolithic humans, not Neanderthals. Furthermore, the Skhul/Qafzeh sample differs significantly from the Neanderthals in many other aspects of hand functional anatomy. Given the correlations between changes in tool technologies and functional adaptations seen in the hands of Upper Paleolithic humans, it is concluded that the Skhul/Qafzeh hand remains were adapted to Upper Paleolithic-like manipulative repertoires. These results support the inference of significant behavioral differences between Neanderthals and the Skhul/Qafzeh hominids and indicate that a significant shift in human manipulative behaviors was associated with the earliest stages of the emergence of modern humans. PMID:11248017

  12. The Obłazowa 1 early modern human pollical phalanx and Late Pleistocene distal thumb proportions.

    PubMed

    Trinkaus, E; Haduch, E; Valde-Nowak, P W; Wojtal, P

    2014-02-01

    The human distal thumb phalanx from the earlier Upper Paleolithic of Obłazowa Cave, southern Poland, exhibits features of its palmar surface that align it morphologically principally with early modern humans. These aspects include the configurations of the proximal palmar fossa, the flexor pollicis longus tendon insertion, the proximal margin of the palmar apical tuft, and especially its low ulnar deviation angle. If it is assumed that it possessed the pollical phalangeal length proportions of an early modern human, it would exhibit modest base and tuft breadths. However, given Late Pleistocene archaic-modern contrasts in relative pollical phalanx lengths, the isolated nature of the phalanx prevents secure assessment of its radioulnar interphalangeal articular and apicaltuft hypertrophy. Similar constraints apply to the assessment of other Pleistocene Homo pollical phalanges. PMID:24616929

  13. Thermoluminescence dating of Neanderthal and early modern humans in the Near East.

    PubMed

    Valladas, H; Valladas, G; Bar-Yosef, O; Vandermeersch, B

    1991-01-01

    Archaeological excavations in Europe provide no evidence for the first modern humans pre-dating Neanderthal man. In the Near East, however, a quite different sequence seems to have pertained. Thermoluminescence dating indicates that at some sites the modern humans were settled some 30,000 years before the Neanderthals. This raises the possibility of two lines of descent from a common ancestor. PMID:1720086

  14. An early modern human from Romania with a recent Neanderthal ancestor.

    PubMed

    Fu, Qiaomei; Hajdinjak, Mateja; Moldovan, Oana Teodora; Constantin, Silviu; Mallick, Swapan; Skoglund, Pontus; Patterson, Nick; Rohland, Nadin; Lazaridis, Iosif; Nickel, Birgit; Viola, Bence; Prüfer, Kay; Meyer, Matthias; Kelso, Janet; Reich, David; Pääbo, Svante

    2015-08-13

    Neanderthals are thought to have disappeared in Europe approximately 39,000-41,000 years ago but they have contributed 1-3% of the DNA of present-day people in Eurasia. Here we analyse DNA from a 37,000-42,000-year-old modern human from Peştera cu Oase, Romania. Although the specimen contains small amounts of human DNA, we use an enrichment strategy to isolate sites that are informative about its relationship to Neanderthals and present-day humans. We find that on the order of 6-9% of the genome of the Oase individual is derived from Neanderthals, more than any other modern human sequenced to date. Three chromosomal segments of Neanderthal ancestry are over 50 centimorgans in size, indicating that this individual had a Neanderthal ancestor as recently as four to six generations back. However, the Oase individual does not share more alleles with later Europeans than with East Asians, suggesting that the Oase population did not contribute substantially to later humans in Europe. PMID:26098372

  15. An early modern human from Romania with a recent Neanderthal ancestor

    PubMed Central

    Fu, Qiaomei; Hajdinjak, Mateja; Moldovan, Oana Teodora; Constantin, Silviu; Mallick, Swapan; Skoglund, Pontus; Patterson, Nick; Rohland, Nadin; Lazaridis, Iosif; Nickel, Birgit; Viola, Bence; Prüfer, Kay; Meyer, Matthias; Kelso, Janet; Reich, David; Pääbo, Svante

    2015-01-01

    Neanderthals are thought to have disappeared in Europe ~39,000–41,000 years ago but they have contributed one to three percent of the DNA of present-day people in Eurasia1. Here, we analyze DNA from a 37,000–42,000-year-old2 modern human from Peştera cu Oase, Romania. Although the specimen contains small amounts of human DNA, we use an enrichment strategy to isolate sites that are informative about its relationship to Neanderthals and present-day humans. We find that on the order of six to nine percent of the genome of the Oase individual is derived from Neanderthals, more than any other modern human sequenced to date. Three chromosomal segments of Neanderthal ancestry are over 50 centimorgans in size, indicating that this individual had a Neanderthal ancestor as recently as four to six generations back. However, the Oase individual does not share more alleles with later Europeans than with East Asians, suggesting that the Oase population did not contribute substantially to later humans in Europe. PMID:26098372

  16. Radiocarbon dating of interstratified Neanderthal and early modern human occupations at the Chatelperronian type-site.

    PubMed

    Gravina, Brad; Mellars, Paul; Ramsey, Christopher Bronk

    2005-11-01

    The question of the coexistence and potential interaction between the last Neanderthal and the earliest intrusive populations of anatomically modern humans in Europe has recently emerged as a topic of lively debate in the archaeological and anthropological literature. Here we report the results of radiocarbon accelerator dating for what has been reported as an interstratified sequence of late Neanderthal and early anatomically modern occupations at the French type-site of the Chatelperronian, the Grotte des Fées de Châtelperron, in east-central France. The radiocarbon measurements seem to provide the earliest secure dates for the presence of Aurignacian technology--and from this, we infer the presence of anatomically modern human populations--in France. PMID:16136079

  17. A humid corridor across the Sahara for the migration of early modern humans out of Africa 120,000 years ago.

    PubMed

    Osborne, Anne H; Vance, Derek; Rohling, Eelco J; Barton, Nick; Rogerson, Mike; Fello, Nuri

    2008-10-28

    It is widely accepted that modern humans originated in sub-Saharan Africa approximately 150-200 thousand years ago (ka), but their route of dispersal across the currently hyperarid Sahara remains controversial. Given that the first modern humans north of the Sahara are found in the Levant approximately 120-90 ka, northward dispersal likely occurred during a humid episode in the Sahara within Marine Isotope Stage (MIS) 5e (130-117 ka). The obvious dispersal route, the Nile, may be ruled out by notable differences between archaeological finds in the Nile Valley and the Levant at the critical time. Further west, space-born radar images reveal networks of-now buried-fossil river channels that extend across the desert to the Mediterranean coast, which represent alternative dispersal corridors. These corridors would explain scattered findings at desert oases of Middle Stone Age Aterian lithic industries with bifacial and tanged points that can be linked with industries further to the east and as far north as the Mediterranean coast. Here we present geochemical data that demonstrate that water in these fossil systems derived from the south during wet episodes in general, and penetrated all of the way to the Mediterranean during MIS 5e in particular. This proves the existence of an uninterrupted freshwater corridor across a currently hyperarid region of the Sahara at a key time for early modern human migrations to the north and out of Africa. PMID:18936490

  18. A humid corridor across the Sahara for the migration of early modern humans out of Africa 120,000 years ago

    PubMed Central

    Osborne, Anne H.; Vance, Derek; Rohling, Eelco J.; Barton, Nick; Rogerson, Mike; Fello, Nuri

    2008-01-01

    It is widely accepted that modern humans originated in sub-Saharan Africa ≈150–200 thousand years ago (ka), but their route of dispersal across the currently hyperarid Sahara remains controversial. Given that the first modern humans north of the Sahara are found in the Levant ≈120–90 ka, northward dispersal likely occurred during a humid episode in the Sahara within Marine Isotope Stage (MIS) 5e (130–117 ka). The obvious dispersal route, the Nile, may be ruled out by notable differences between archaeological finds in the Nile Valley and the Levant at the critical time. Further west, space-born radar images reveal networks of—now buried—fossil river channels that extend across the desert to the Mediterranean coast, which represent alternative dispersal corridors. These corridors would explain scattered findings at desert oases of Middle Stone Age Aterian lithic industries with bifacial and tanged points that can be linked with industries further to the east and as far north as the Mediterranean coast. Here we present geochemical data that demonstrate that water in these fossil systems derived from the south during wet episodes in general, and penetrated all of the way to the Mediterranean during MIS 5e in particular. This proves the existence of an uninterrupted freshwater corridor across a currently hyperarid region of the Sahara at a key time for early modern human migrations to the north and out of Africa. PMID:18936490

  19. A humid corridor across the Sahara for the migration "Out of Africa" of early modern humans 120,000 years ago

    NASA Astrophysics Data System (ADS)

    Osborne, A. H.; Vance, D.; Rohling, E. J.; Barton, N.; Rogerson, M.; Fello, N.

    2008-12-01

    The climatic history of the Sahara in the Quaternary is likely to have been a key control on the history of human migrations out of Africa. For example, it is widely accepted that modern humans originated in sub- Saharan Africa around 150-200 thousand years ago (ka), but their route of dispersal across the currently hyper-arid Sahara remains controversial. Given that the first modern humans north of the Sahara are found in the Levant around 120-90 ka, northward dispersal likely occurred during the humid episode in the Sahara within Marine Isotope Stage (MIS) 5e (130-117 ka). The obvious dispersal route, the Nile, may be ruled out by notable differences between archaeological finds in the Nile Valley and the Levant at the critical time. Further west, space-born radar images reveal networks of - now buried - fossil river channels that extend across the desert to the Mediterranean coast, which represent alternative dispersal corridors. This would explain scattered findings at desert oases of Middle Stone Age (MSA) Aterian lithic industries with bifacial and tanged points that can be linked with industries further to the east and as far north as the Mediterranean coast. We have previously used neodymium and oxygen isotope data to suggest that there was enhanced Nile outflow to the Levantine Sea during Saharan humid periods in Stage 5e and the Holocene1. Here, however, we present further geochemical data which suggest that the freshwater signal from Africa was much stronger further west in the Ionian Sea. Furthermore, analyses of shell samples retrieved from the Libyan fossil river channels traces the geochemical signature found in the Ionian Sea to the Tibesti Mountains in the southern Sahara. These data demonstrate that water in the fossil river systems of the Sahara derived from the south during wet episodes in general, and penetrated all the way to the Mediterranean during MIS 5e in particular, confirming the existence of an uninterrupted freshwater corridor across a currently hyperarid region of the Sahara at a key time for early modern human migrations to the north and out of Africa. 1Scrivner, A.E. et al. (2004) Geology 32, 565-568.

  20. Preterit Loss in Early Modern Nuremberg

    ERIC Educational Resources Information Center

    Bagwell, Angela Catania

    2013-01-01

    This study investigates "Prateritumschwund," one of the most salient developments in the Upper German dialect area during the Early Modern period. Drawing on a wide range of text types originating in Nuremberg and its surrounding areas from the 13th to the 17th centuries, this study tests various hypotheses put forward as alleged causes…

  1. Early modern experimentation on live animals.

    PubMed

    Bertoloni Meli, Domenico

    2013-01-01

    Starting from the works by Aselli (De lactibus sive lacteis venis, 1627) on the milky veins and Harvey (1628, translated in 1993) on the motion of the heart and the circulation of the blood, the practice of vivisection witnessed a resurgence in the early modern period. I discuss some of the most notable cases in the century spanning from Aselli's work to the investigations of fluid pressure in plants and animals by Stephen Hales (Vegetable Staticks, 1727). Key figures in my study include Johannes Walaeus, Jean Pecquet, Marcello Malpighi, Reinier de Graaf, Richard Lower, Anton Nuck, and Anton de Heide. Although vivisection dates from antiquity, early modern experimenters expanded the range of practices and epistemic motivations associated with it, displaying considerable technical skills and methodological awareness about the problems associated with the animals being alive and the issue of generalizing results to humans. Many practitioners expressed great discomfort at the suffering of the animals; however, many remained convinced that their investigations were not only indispensable from an epistemic standpoint but also had potential medical applications. Early modern vivisection experiments were both extensive and sophisticated and cannot be ignored in the literature of early modern experimentation or of experimentation on living organisms across time. PMID:22684270

  2. Implications of Nubian-Like Core Reduction Systems in Southern Africa for the Identification of Early Modern Human Dispersals

    PubMed Central

    Phillips, Natasha

    2015-01-01

    Lithic technologies have been used to trace dispersals of early human populations within and beyond Africa. Convergence in lithic systems has the potential to confound such interpretations, implying connections between unrelated groups. Due to their reductive nature, stone artefacts are unusually prone to this chance appearance of similar forms in unrelated populations. Here we present data from the South African Middle Stone Age sites Uitpanskraal 7 and Mertenhof suggesting that Nubian core reduction systems associated with Late Pleistocene populations in North Africa and potentially with early human migrations out of Africa in MIS 5 also occur in southern Africa during early MIS 3 and with no clear connection to the North African occurrence. The timing and spatial distribution of their appearance in southern and northern Africa implies technological convergence, rather than diffusion or dispersal. While lithic technologies can be a critical guide to human population flux, their utility in tracing early human dispersals at large spatial and temporal scales with stone artefact types remains questionable. PMID:26125972

  3. Digit ratios predict polygyny in early apes, Ardipithecus, Neanderthals and early modern humans but not in Australopithecus

    PubMed Central

    Nelson, Emma; Rolian, Campbell; Cashmore, Lisa; Shultz, Susanne

    2011-01-01

    Social behaviour of fossil hominoid species is notoriously difficult to predict owing to difficulties in estimating body size dimorphism from fragmentary remains and, in hominins, low canine size dimorphism. Recent studies have shown that the second-to-fourth digit ratio (2D : 4D), a putative biomarker for prenatal androgen effects (PAEs), covaries with intra-sexual competition and social systems across haplorrhines; non-pair-bonded polygynous taxa have significantly lower 2D : 4D ratios (high PAE) than pair-bonded monogamous species. Here, we use proximal phalanx ratios of extant and fossil specimens to reconstruct the social systems of extinct hominoids. Pierolapithecus catalaunicus, Hispanopithecus laietanus and Ardipithecus ramidus have ratios consistent with polygynous extant species, whereas the ratio of Australopithecus afarensis is consistent with monogamous extant species. The early anatomically modern human Qafzeh 9 and Neanderthals have lower digit ratios than most contemporary human populations, indicating increased androgenization and possibly higher incidence of polygyny. Although speculative owing to small sample sizes, these results suggest that digit ratios represent a supplementary approach for elucidating the social systems of fossil hominins. PMID:21047863

  4. Digit ratios predict polygyny in early apes, Ardipithecus, Neanderthals and early modern humans but not in Australopithecus.

    PubMed

    Nelson, Emma; Rolian, Campbell; Cashmore, Lisa; Shultz, Susanne

    2011-05-22

    Social behaviour of fossil hominoid species is notoriously difficult to predict owing to difficulties in estimating body size dimorphism from fragmentary remains and, in hominins, low canine size dimorphism. Recent studies have shown that the second-to-fourth digit ratio (2D : 4D), a putative biomarker for prenatal androgen effects (PAEs), covaries with intra-sexual competition and social systems across haplorrhines; non-pair-bonded polygynous taxa have significantly lower 2D : 4D ratios (high PAE) than pair-bonded monogamous species. Here, we use proximal phalanx ratios of extant and fossil specimens to reconstruct the social systems of extinct hominoids. Pierolapithecus catalaunicus, Hispanopithecus laietanus and Ardipithecus ramidus have ratios consistent with polygynous extant species, whereas the ratio of Australopithecus afarensis is consistent with monogamous extant species. The early anatomically modern human Qafzeh 9 and Neanderthals have lower digit ratios than most contemporary human populations, indicating increased androgenization and possibly higher incidence of polygyny. Although speculative owing to small sample sizes, these results suggest that digit ratios represent a supplementary approach for elucidating the social systems of fossil hominins. PMID:21047863

  5. Dental wear patterns in early modern humans from Skhul and Qafzeh: A response to Sarig and Tillier.

    PubMed

    Fiorenza, Luca; Kullmer, Ottmar

    2015-10-01

    The use of teeth as tools for manipulating objects and simple food-processing methods was common among prehistoric and modern hunter-gatherer human populations. Paramasticatory uses of teeth frequently produce enamel chipping and distinctive types of dental wear that can readily be related to specific tool functions. In particular, the presence of unusual occlusal wear areas (named para-facets) on maxillary teeth of prehistoric, historic and modern hunter-gatherers has been associated with cultural habits involving extensive use of teeth (Fiorenza et al., 2011; Fiorenza and Kullmer, 2013). However, Sarig and Tillier (2014) believe that this wear had been caused by pathological occlusal relationships rather than by the use of teeth as tools. In this contribution, we show how occlusal contacts are created and how it is possible to distinguish between masticatory and non-masticatory wear facets by using an innovative digital approach called Occlusal Fingerprint Analysis. Statistical results from the analysis of comparative modern samples clearly demonstrate that described para-facets in Skhul and Qafzeh could not have been produced by dental occlusal anomalies such as malocclusions and crossbites. Moreover, dental pathologies in prehistoric humans were extremely rare. Only with the adoption of the modern lifestyle between 18th and 19th centuries, did the emergence of malocclusions become significantly more common. Because more than 50% of the Skhul and Qafzeh individuals analysed in our study are characterised by this distinctive type of wear, it is highly unlikely that their para-facets occurred as a result of dental pathologies. PMID:26048367

  6. Distal tephras of the eastern Lake Victoria basin, equatorial East Africa: correlations, chronology and a context for early modern humans

    NASA Astrophysics Data System (ADS)

    Blegen, Nick; Tryon, Christian A.; Faith, J. Tyler; Peppe, Daniel J.; Beverly, Emily J.; Li, Bo; Jacobs, Zenobia

    2015-08-01

    The tephrostratigraphic framework for Pliocene and Early Pleistocene paleoanthropological sites in East Africa has been well established through nearly 50 years of research, but a similarly comprehensive framework is lacking for the Middle and particularly the Late Pleistocene. We provide the first detailed regional record of Late Pleistocene tephra deposits associated with artifacts or fossils from the Lake Victoria basin of western Kenya. Correlations of Late Pleistocene distal tephra deposits from the Wasiriya beds on Rusinga Island, the Waware beds on Mfangano Island and deposits near Karungu, mainland Kenya, are based on field stratigraphy coupled with 916 electron microprobe analyses of eleven major and minor element oxides from 50 samples. At least eight distinct distal tephra deposits are distinguished, four of which are found at multiple localities spanning >60 km over an approximately north to south transect. New optically stimulated luminescence dates help to constrain the Late Pleistocene depositional ages of these deposits. Our correlation and characterization of volcaniclastic deposits expand and refine the current stratigraphy of the eastern Lake Victoria basin. This provides the basis for relating fossil- and artifact-bearing sediments and a framework for ongoing geological, archaeological and paleontological studies of Late Pleistocene East Africa, a crucial time period for human evolution and dispersal within and out of Africa.

  7. Casebooks in Early Modern England:

    PubMed Central

    Kassell, Lauren

    2014-01-01

    summary Casebooks are the richest sources that we have for encounters between early modern medical practitioners and their patients. This article compares astrological and medical records across two centuries, focused on England, and charts developments in the ways in which practitioners kept records and reflected on their practices. Astrologers had a long history of working from particular moments, stellar configurations, and events to general rules. These practices required systematic notation. Physicians increasingly modeled themselves on Hippocrates, recording details of cases as the basis for reasoned expositions of the histories of disease. Medical records, as other scholars have demonstrated, shaped the production of medical knowledge. Instead, this article focuses on the nature of casebooks as artifacts of the medical encounter. It establishes that casebooks were serial records of practice, akin to diaries, testimonials, and registers; identifies extant English casebooks and the practices that led to their production and preservation; and concludes that the processes of writing, ordering, and preserving medical records are as important for understanding the medical encounter as the records themselves. PMID:25557513

  8. The Corporeality of Learning: Confucian Education in Early Modern Japan

    ERIC Educational Resources Information Center

    Tsujimoto, Masashi

    2016-01-01

    The intellectual foundation of early modern Japan was provided by Confucianism--a system of knowledge set forth in Chinese classical writings. In order to gain access to this knowledge, the Japanese applied reading markers to modify the original Chinese to fit the peculiarities of Japanese grammar and pronunciation. Confucian education started by…

  9. The Corporeality of Learning: Confucian Education in Early Modern Japan

    ERIC Educational Resources Information Center

    Tsujimoto, Masashi

    2016-01-01

    The intellectual foundation of early modern Japan was provided by Confucianism--a system of knowledge set forth in Chinese classical writings. In order to gain access to this knowledge, the Japanese applied reading markers to modify the original Chinese to fit the peculiarities of Japanese grammar and pronunciation. Confucian education started by

  10. Early modern human settlement of Europe north of the Alps occurred 43,500 years ago in a cold steppe-type environment.

    PubMed

    Nigst, Philip R; Haesaerts, Paul; Damblon, Freddy; Frank-Fellner, Christa; Mallol, Carolina; Viola, Bence; Götzinger, Michael; Niven, Laura; Trnka, Gerhard; Hublin, Jean-Jacques

    2014-10-01

    The first settlement of Europe by modern humans is thought to have occurred between 50,000 and 40,000 calendar years ago (cal B.P.). In Europe, modern human remains of this time period are scarce and often are not associated with archaeology or originate from old excavations with no contextual information. Hence, the behavior of the first modern humans in Europe is still unknown. Aurignacian assemblages--demonstrably made by modern humans--are commonly used as proxies for the presence of fully behaviorally and anatomically modern humans. The site of Willendorf II (Austria) is well known for its Early Upper Paleolithic horizons, which are among the oldest in Europe. However, their age and attribution to the Aurignacian remain an issue of debate. Here, we show that archaeological horizon 3 (AH 3) consists of faunal remains and Early Aurignacian lithic artifacts. By using stratigraphic, paleoenvironmental, and chronological data, AH 3 is ascribed to the onset of Greenland Interstadial 11, around 43,500 cal B.P., and thus is older than any other Aurignacian assemblage. Furthermore, the AH 3 assemblage overlaps with the latest directly radiocarbon-dated Neanderthal remains, suggesting that Neanderthal and modern human presence overlapped in Europe for some millennia, possibly at rather close geographical range. Most importantly, for the first time to our knowledge, we have a high-resolution environmental context for an Early Aurignacian site in Central Europe, demonstrating an early appearance of behaviorally modern humans in a medium-cold steppe-type environment with some boreal trees along valleys around 43,500 cal B.P. PMID:25246543

  11. Early modern human settlement of Europe north of the Alps occurred 43,500 years ago in a cold steppe-type environment

    PubMed Central

    Nigst, Philip R.; Haesaerts, Paul; Damblon, Freddy; Frank-Fellner, Christa; Mallol, Carolina; Viola, Bence; Götzinger, Michael; Niven, Laura; Trnka, Gerhard; Hublin, Jean-Jacques

    2014-01-01

    The first settlement of Europe by modern humans is thought to have occurred between 50,000 and 40,000 calendar years ago (cal B.P.). In Europe, modern human remains of this time period are scarce and often are not associated with archaeology or originate from old excavations with no contextual information. Hence, the behavior of the first modern humans in Europe is still unknown. Aurignacian assemblages—demonstrably made by modern humans—are commonly used as proxies for the presence of fully behaviorally and anatomically modern humans. The site of Willendorf II (Austria) is well known for its Early Upper Paleolithic horizons, which are among the oldest in Europe. However, their age and attribution to the Aurignacian remain an issue of debate. Here, we show that archaeological horizon 3 (AH 3) consists of faunal remains and Early Aurignacian lithic artifacts. By using stratigraphic, paleoenvironmental, and chronological data, AH 3 is ascribed to the onset of Greenland Interstadial 11, around 43,500 cal B.P., and thus is older than any other Aurignacian assemblage. Furthermore, the AH 3 assemblage overlaps with the latest directly radiocarbon-dated Neanderthal remains, suggesting that Neanderthal and modern human presence overlapped in Europe for some millennia, possibly at rather close geographical range. Most importantly, for the first time to our knowledge, we have a high-resolution environmental context for an Early Aurignacian site in Central Europe, demonstrating an early appearance of behaviorally modern humans in a medium-cold steppe-type environment with some boreal trees along valleys around 43,500 cal B.P. PMID:25246543

  12. Bolatu's pharmacy theriac in early modern China.

    PubMed

    Nappi, Carla

    2009-01-01

    In early modem China, natural history and medicine were shifting along with the boundaries of the empire. Naturalists struggled to cope with a pharmacy's worth of new and unfamiliar substances, texts, and terms, as plants, animals, and the drugs made from them travelled into China across land and sea. One crucial aspect of this phenomenon was the early modern exchange between Islamic and Chinese medicine. The history of theriac illustrates the importance of the recipe for the naturalization of foreign objects in early modem Chinese medicine. Theriac was a widely sought-after and hotly debated product in early modern European pharmacology and arrived into the Chinese medical canon via Arabic and Persian texts. The dialogue between language and material objects was critical to the Silk Road drug trade, and transliteration was ultimately a crucial technology used to translate drugs and texts about them in the early modern world. PMID:20509359

  13. Genetic evidence and the modern human origins debate.

    PubMed

    Relethford, J H

    2008-06-01

    A continued debate in anthropology concerns the evolutionary origin of 'anatomically modern humans' (Homo sapiens sapiens). Different models have been proposed to examine the related questions of (1) where and when anatomically modern humans first appeared and (2) the genetic and evolutionary relationship between modern humans and earlier human populations. Genetic data have been increasingly used to address these questions. Genetic data on living human populations have been used to reconstruct the evolutionary history of the human species by considering how global patterns of human variation could be produced given different evolutionary scenarios. Of particular interest are gene trees that reconstruct the time and place of the most recent common ancestor of humanity for a given haplotype and the analysis of regional differences in genetic diversity. Ancient DNA has also allowed a direct assessment of genetic variation in European Neandertals. Together with the fossil record, genetic data provide insight into the origin of modern humans. The evidence points to an African origin of modern humans dating back to 200,000 years followed by later expansions of moderns out of Africa across the Old World. What is less clear is what happened when these early modern humans met preexisting 'archaic human' populations outside of Africa. At present, it is difficult to distinguish between a model of total genetic replacement and a model that includes some degree of genetic mixture. PMID:18322457

  14. Being Mad in Early Modern England

    PubMed Central

    Dimitrijevic, Aleksandar

    2015-01-01

    It has become almost a rule that the birth of scientific psychiatry and what we today term clinical psychology took place in the short period between the last decade of the XVIII century and the 1820s. Everything that happened before that period—every description, diagnosis, and therapy—has been considered “pre-scientific,” outdated, in a way worthless. In this paper, however, I am providing the argument that, first, the roots of contemporary psychiatry reach at least to England of the early modern period, and that, second, it may still turn out that in the field of mental health care historical continuities are more numerous and persistent than discontinuities. Thus, I briefly review the most important surviving documents about the treatment of mental disorders in England of Elizabethan and Jacobian period, organizing the argument around the well-known markers: diagnostics and etiology, therapy, organization of the asylum, the public image of the mentally ill. PMID:26635656

  15. Being Mad in Early Modern England.

    PubMed

    Dimitrijevic, Aleksandar

    2015-01-01

    It has become almost a rule that the birth of scientific psychiatry and what we today term clinical psychology took place in the short period between the last decade of the XVIII century and the 1820s. Everything that happened before that period-every description, diagnosis, and therapy-has been considered "pre-scientific," outdated, in a way worthless. In this paper, however, I am providing the argument that, first, the roots of contemporary psychiatry reach at least to England of the early modern period, and that, second, it may still turn out that in the field of mental health care historical continuities are more numerous and persistent than discontinuities. Thus, I briefly review the most important surviving documents about the treatment of mental disorders in England of Elizabethan and Jacobian period, organizing the argument around the well-known markers: diagnostics and etiology, therapy, organization of the asylum, the public image of the mentally ill. PMID:26635656

  16. Trading Zones in Early Modern Europe.

    PubMed

    Long, Pamela O

    2015-12-01

    This essay adopts the concept of trading zones first developed for the history of science by Peter Galison and redefines it for the early modern period. The term "trading zones" is used to mean arenas in which substantive and reciprocal communication occurred between individuals who were artisanally trained and learned (university-trained) individuals. Such trading zones proliferated in the sixteenth century. They tended to arise in certain kinds of places and not in others, but their existence must be determined empirically. The author's work on trading zones differs from the ideas of Edgar Zilsel, who emphasized the influence of artisans on the scientific revolution. In contrast, in this essay, the mutual influence of artisans and the learned on each other is stressed, and translation is used as a modality that was important to communication within trading zones. PMID:27024940

  17. Medieval and early modern theories of mental illness.

    PubMed

    Neugebauer, R

    1979-04-01

    Historians of medieval and early modern psychiatry have utilized limited source materials in their research. They have focused on printed works, particularly formal treatises by celebrated authors, and neglected manuscript collections. The resulting histories depict early European psychiatric thought as dominated by demonology. Examination of the archives of an early English legal incompetency jurisdiction flatly contradicts this picture. Starting in the 13th century, the English government conducted mental status examinations of psychiatrically disabled individuals, using commonsense, naturalistic criteria of impairment; private, supervised guardians were appointed for such persons. Furthermore, etiological theories entertained by royal officials and laymen relied on physiological and psychological notions of psychiatric illness. These findings raise serious questions about conventional accounts of this period and underline the need for more research using original manuscripts. PMID:371576

  18. Ancient humans and the origin of modern humans.

    PubMed

    Kelso, Janet; Prüfer, Kay

    2014-12-01

    Recent advances in sequencing technologies and molecular methods have facilitated the sequencing of DNA from ancient human remains which has, in turn, provided unprecedented insight into human history. Within the past 4 years the genomes of Neandertals and Denisovans, as well as the genomes of at least two early modern humans, have been sequenced. These sequences showed that there have been several episodes of admixture between modern and archaic groups; including admixture from Neandertals into modern human populations outside of Africa, and admixture from Denisovans into modern human populations in Oceania. Recent results indicate that some of these introgressed regions may have been advantageous for modern humans as they expanded into new regions outside of Africa. PMID:25286439

  19. Two medieval plague treatises and their afterlife in early modern England.

    PubMed

    Keiser, George R

    2003-07-01

    This study of an adaptation of the popular John of Burgundy plague treatise by Thomas Moulton, a Dominican friar, ca. 1475, and a translation of the so-called Canutus plague treatise by Thomas Paynell, printed 1534, shows how the medieval traditions they represent were carried forward, well into the sixteenth century, and also subjected to change in light of religious, moral, and medical concerns of early modern England. The former had a long life in print, ca. 1530-1580, whereas Paynell's translation exists in one printed version. Moulton's adaptation differs from its original and from the Canutus treatise in putting great emphasis on the idea that onsets of plague were acts of divine retribution for human sinfulness. In this respect, Moulton reshaped the tradition of the medieval plague treatise and anticipated the religious and social construction of plague that would take shape in the first half of the sixteenth century. Its long history in print indicates that Moulton's treatise expressed the spirit of that construction and probably influenced the construction as well. The contrasting histories of the two treatises attest not only to the dramatic change brought about by religious and social forces in the sixteenth century, but to a growing recognition of the value of the printing press for disseminating medical information-in forms that served social and ideological ends. PMID:12938716

  20. Bat origin of human coronaviruses.

    PubMed

    Hu, Ben; Ge, Xingyi; Wang, Lin-Fa; Shi, Zhengli

    2015-01-01

    Bats have been recognized as the natural reservoirs of a large variety of viruses. Special attention has been paid to bat coronaviruses as the two emerging coronaviruses which have caused unexpected human disease outbreaks in the 21st century, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), are suggested to be originated from bats. Various species of horseshoe bats in China have been found to harbor genetically diverse SARS-like coronaviruses. Some strains are highly similar to SARS-CoV even in the spike protein and are able to use the same receptor as SARS-CoV for cell entry. On the other hand, diverse coronaviruses phylogenetically related to MERS-CoV have been discovered worldwide in a wide range of bat species, some of which can be classified to the same coronavirus species as MERS-CoV. Coronaviruses genetically related to human coronavirus 229E and NL63 have been detected in bats as well. Moreover, intermediate hosts are believed to play an important role in the transmission and emergence of these coronaviruses from bats to humans. Understanding the bat origin of human coronaviruses is helpful for the prediction and prevention of another pandemic emergence in the future. PMID:26689940

  1. "Old Poems Have Heart": Teenage Students Reading Early Modern Poetry

    ERIC Educational Resources Information Center

    Naylor, Amanda

    2013-01-01

    The proposals for the revised National Curriculum in English suggest limiting the pre-twentieth century poetry that GCSE pupils read to "representative Romantic poetry" (Department for Education [DFE], 2013, p. 4). This paper argues that poetry of the early modern period is challenging and enriching study for adolescent pupils and that…

  2. Evidence for a (15)N positive excursion in terrestrial foodwebs at the Middle to Upper Palaeolithic transition in south-western France: Implications for early modern human palaeodiet and palaeoenvironment.

    PubMed

    Bocherens, Hervé; Drucker, Dorothée G; Madelaine, Stéphane

    2014-04-01

    The Middle to Upper Palaeolithic transition around 35,000 years ago coincides with the replacement of Neanderthals by anatomically modern humans in Europe. Several hypotheses have been suggested to explain this replacement, one of them being the ability of anatomically modern humans to broaden their dietary spectrum beyond the large ungulate prey that Neanderthals consumed exclusively. This scenario is notably based on higher nitrogen-15 amounts in early Upper Palaeolithic anatomically modern human bone collagen compared with late Neanderthals. In this paper, we document a clear increase of nitrogen-15 in bone collagen of terrestrial herbivores during the early Aurignacian associated with anatomically modern humans compared with the stratigraphically older Châtelperronian and late Mousterian fauna associated with Neanderthals. Carnivores such as wolves also exhibit a significant increase in nitrogen-15, which is similar to that documented for early anatomically modern humans compared with Neanderthals in Europe. A shift in nitrogen-15 at the base of the terrestrial foodweb is responsible for such a pattern, with a preserved foodweb structure before and after the Middle to Upper Palaeolithic transition in south-western France. Such an isotopic shift in the terrestrial ecosystem may be due to an increase in aridity during the time of deposition of the early Aurignacian layers. If it occurred across Europe, such a shift in nitrogen-15 in terrestrial foodwebs would be enough to explain the observed isotopic trend between late Neanderthals and early anatomically modern humans, without any significant change in the diet composition at the Middle to Upper Palaeolithic transition. PMID:24630359

  3. Human origins: Out of Africa

    PubMed Central

    Tattersall, Ian

    2009-01-01

    Our species, Homo sapiens, is highly autapomorphic (uniquely derived) among hominids in the structure of its skull and postcranial skeleton. It is also sharply distinguished from other organisms by its unique symbolic mode of cognition. The fossil and archaeological records combine to show fairly clearly that our physical and cognitive attributes both first appeared in Africa, but at different times. Essentially modern bony conformation was established in that continent by the 200–150 Ka range (a dating in good agreement with dates for the origin of H. sapiens derived from modern molecular diversity). The event concerned was apparently short-term because it is essentially unanticipated in the fossil record. In contrast, the first convincing stirrings of symbolic behavior are not currently detectable until (possibly well) after 100 Ka. The radical reorganization of gene expression that underwrote the distinctive physical appearance of H. sapiens was probably also responsible for the neural substrate that permits symbolic cognition. This exaptively acquired potential lay unexploited until it was “discovered” via a cultural stimulus, plausibly the invention of language. Modern humans appear to have definitively exited Africa to populate the rest of the globe only after both their physical and cognitive peculiarities had been acquired within that continent. PMID:19805256

  4. Marginalia, commonplaces, and correspondence: scribal exchange in early modern science.

    PubMed

    Yale, Elizabeth

    2011-06-01

    In recent years, historians of science have increasingly turned their attention to the "print culture" of early modern science. These studies have revealed that printing, as both a technology and a social and economic system, structured the forms and meanings of natural knowledge. Yet in early modern Europe, naturalists, including John Aubrey, John Evelyn, and John Ray, whose work is discussed in this paper, often shared and read scientific texts in manuscript either before or in lieu of printing. Scribal exchange, exemplified in the circulation of writings like commonplace books, marginalia, manuscript treatises, and correspondence, was the primary means by which communities of naturalists constructed scientific knowledge. Print and manuscript were necessary partners. Manuscript fostered close collaboration, and could be circulated relatively cheaply; but, unlike print, it could not reliably secure priority or survival for posterity. Naturalists approached scribal and print communication strategically, choosing the medium that best suited their goals at any given moment. As a result, print and scribal modes of disseminating information, constructing natural knowledge, and organizing communities developed in tandem. Practices typically associated with print culture manifested themselves in scribal texts and exchanges, and vice versa. "Print culture" cannot be hived off from "scribal culture." Rather, in their daily jottings and exchanges, naturalists inhabited, and produced, one common culture of communication. PMID:21486658

  5. Assembling the dodo in early modern natural history.

    PubMed

    Lawrence, Natalie

    2015-09-01

    This paper explores the assimilation of the flightless dodo into early modern natural history. The dodo was first described by Dutch sailors landing on Mauritius in 1598, and became extinct in the 1680s or 1690s. Despite this brief period of encounter, the bird was a popular subject in natural-history works and a range of other genres. The dodo will be used here as a counterexample to the historical narratives of taxonomic crisis and abrupt shifts in natural history caused by exotic creatures coming to Europe. Though this bird had a bizarre form, early modern naturalists integrated the dodo and other flightless birds through several levels of conceptual categorization, including the geographical, morphological and symbolic. Naturalists such as Charles L'Ecluse produced a set of typical descriptive tropes that helped make up the European dodo. These long-lived images were used for a variety of symbolic purposes, demonstrated by the depiction of the Dutch East India enterprise in Willem Piso's 1658 publication. The case of the dodo shows that, far from there being a dramatic shift away from emblematics in the seventeenth century, the implicit symbolic roles attributed to exotic beasts by naturalists constructing them from scant information and specimens remained integral to natural history. PMID:26256311

  6. Renaissance plays as a useful source for the comparison between English and Croatian early modern medicine.

    PubMed

    Atalic, Bruno

    2012-01-01

    This paper evaluates the differences between English and Croatian views of early modern medicine through the respective Renaissance plays. As Renaissance made no particular distinction between arts and sciences, plays of that time provide a very common source of medical narrative. During Renaissance both languages produced high literary achievements, which makes them exemplars among their Germanic and Slavic counterparts, and justifies this comparison, regardless of their significant differences. One should bear in mind that while England was a unified kingdom, with London as the major cultural centre, Croatia's division among the neighbouring powers produced several prominent cultural centres such as Zadar, Šibenik, Split, Hvar, Korčula, and the most important one, Dubrovnik. One should also bear in mind that the golden age of Croatian Renaissance plays had finished as early as 1567 with the death of Marin DrŽić, before it even started in England with the foundation of the first permanent theatrical companies in 1576. Along these lines, this paper compares their early modern attitudes toward medicine in general and men and women practitioners in particular. In this respect, it evaluates the influences of the origin, patronage, and religion of their authors. Special attention is given to William Shakespeare (1564-1616) and Marin DrŽić (1508-1567) as the exemplars of English and Croatian Renaissance literature. PMID:23094840

  7. Assessing an early modern Fenland population: Whittlesey (Cambridgeshire).

    PubMed

    Falvey, Heather

    2014-01-01

    Improvement writers argued that drainage would bring prosperity and population growth to fenland communities; locals counter-argued that their communities were already thriving. The detailed surviving records from early modern Whittlesey, in the Isle of Ely, are analysed here to test the accuracy of these opposing claims. Using the returns of the 1523 Lay Subsidy, the 1563 ecclesiastical census, the Lady Day 1674 Hearth Tax records and the 1676 Compton Census, together with bishops' transcripts and probate inventories, this article finds that although the population did indeed increase after drainage, the pre-drainage population was also increasing. The Michaelmas 1664 Hearth Tax records are analysed to uncover something of the character of the inhabitants and the 1674 Lady Day returns are then used to test the relative wealth of the community compared with that of sub-regions throughout England identified by Tom Arkell. Finally, there is a discussion of Whittlesey's housing stock. PMID:25080616

  8. The fourfold Democritus on the stage of early modern science.

    PubMed

    Lüthy, C

    2000-09-01

    The renewed success of ancient atomism in the seventeenth century has baffled historians not only because of the lack of empirical evidence in its favor but also because of the exotic heterogeneity of the models that were proposed under its name. This essay argues that one of the more intriguing reasons for the motley appearance of early modern atomism is that Democritus, with whose name this doctrine was most commonly associated, was a figure of similar incoherence. There existed in fact no fewer than four quite different Democriti of Abdera and as many literary traditions: the atomist, the "laughing philosopher," the moralizing anatomist, and the alchemist. Around the year 1600 the doctrines of these literary figures, three of whom had no tangible connection with atomism, began to merge into further hybrid personae, some of whom possessed notable scientific potential. This essay offers the story of how these Democriti contributed to the rise of incompatible "atomisms." PMID:11143784

  9. Wombs, Worms and Wolves: Constructing Cancer in Early Modern England

    PubMed Central

    Skuse, Alanna

    2014-01-01

    This essay examines medical and popular attitudes to cancer in the early modern period, c.1580–1720. Cancer, it is argued, was understood as a cruel and usually incurable disease, diagnosable by a well-defined set of symptoms understood to correspond to its etymological root, karkinos (the crab). It was primarily understood as produced by an imbalance of the humours, with women being particularly vulnerable. However, such explanations proved inadequate to make sense of the condition's malignancy, and medical writers frequently constructed cancer as quasi-sentient, zoomorphising the disease as an eating worm or wolf. In turn, these constructions materially influenced medical practice, in which practitioners swung between anxiety over ‘aggravating’ the disease and an adversarial approach which fostered the use of radical and dangerous ‘cures’ including caustics and surgery. PMID:25352720

  10. Human embryos in the original position?

    PubMed

    DiSilvestro, Russell

    2005-06-01

    Two different discussions in John Rawls' A Theory of Justice lead naturally to a rather conservative position on the moral status of the human embryo. When discussing paternalism, he claims that the parties in the original position would seek to protect themselves in case they end up as incapacitated or undeveloped human beings when the veil of ignorance is lifted. Since human embryos are examples of such beings, the parties in the original position would seek to protect themselves from their embryonic stages onward. When discussing the basis of equality, Rawls claims that the parties in the original position would guarantee basic rights for all those with the capacity to take part in this original position. To guarantee the basic rights of infants and young children, he goes on to interpret this capacity as a "potentiality that is ordinarily realized in due course." Since human embryos have this potentiality, they too should have basic rights. PMID:16036460

  11. Demons, nature, or God? Witchcraft accusations and the French disease in early modern Venice.

    PubMed

    McGough, Laura J

    2006-01-01

    In early modern Venice, establishing the cause of a disease was critical to determining the appropriate cure: natural remedies for natural illnesses, spiritual solutions for supernatural or demonic ones. One common ailment was the French disease (syphilis), widely distributed throughout Venice's neighborhoods and social hierarchy, and evenly distributed between men and women. The disease was widely regarded as curable by the mid-sixteenth century, and cases that did not respond to natural remedies presented problems of interpretation to physicians and laypeople. Witchcraft was one possible explanation; using expert testimony from physicians, however, the Holy Office ruled out witchcraft as a cause of incurable cases and reinforced perceptions that the disease was of natural origin. Incurable cases were explained as the result of immoral behavior, thereby reinforcing the associated stigma. This article uses archival material from Venice's Inquisition records from 1580 to 1650, as well as mortality data. PMID:16809862

  12. Casebooks in early modern England: medicine, astrology, and written records.

    PubMed

    Kassell, Lauren

    2014-01-01

    Casebooks are the richest sources that we have for encounters between early modern medical practitioners and their patients. This article compares astrological and medical records across two centuries, focused on England, and charts developments in the ways in which practitioners kept records and reflected on their practices. Astrologers had a long history of working from particular moments, stellar configurations, and events to general rules. These practices required systematic notation. Physicians increasingly modeled themselves on Hippocrates, recording details of cases as the basis for reasoned expositions of the histories of disease. Medical records, as other scholars have demonstrated, shaped the production of medical knowledge. Instead, this article focuses on the nature of casebooks as artifacts of the medical encounter. It establishes that casebooks were serial records of practice, akin to diaries, testimonials, and registers; identifies extant English casebooks and the practices that led to their production and preservation; and concludes that the processes of writing, ordering, and preserving medical records are as important for understanding the medical encounter as the records themselves. PMID:25557513

  13. Erotic Love and the Development of Proto-Capitalist Ideology in Early Modern Comedy

    ERIC Educational Resources Information Center

    Damsen, Silver

    2009-01-01

    My dissertation, "Erotic Love and the Development of Proto-Capitalist Ideology in Early Modern Comedy" demonstrates how increased crown authority, and an expanded market combine with the mixed agency of the romantic comedy daughter to further encourage early modern economic growth. The triumph of rebelling daughter over blocking father has

  14. Erotic Love and the Development of Proto-Capitalist Ideology in Early Modern Comedy

    ERIC Educational Resources Information Center

    Damsen, Silver

    2009-01-01

    My dissertation, "Erotic Love and the Development of Proto-Capitalist Ideology in Early Modern Comedy" demonstrates how increased crown authority, and an expanded market combine with the mixed agency of the romantic comedy daughter to further encourage early modern economic growth. The triumph of rebelling daughter over blocking father has…

  15. Identifying the seasonal origins of human campylobacteriosis

    PubMed Central

    STRACHAN, N. J. C.; ROTARIU, O.; SMITH-PALMER, A.; COWDEN, J.; SHEPPARD, S. K.; O’BRIEN, S. J.; MAIDEN, M. C. J.; MACRAE, M.; BESSELL, P. R.; MATTHEWS, L.; REID, S. W. J.; INNOCENT, G. T.; OGDEN, I. D.; FORBES, K. J.

    2014-01-01

    SUMMARY Human campylobacteriosis exhibits a distinctive seasonality in temperate regions. This paper aims to identify the origins of this seasonality. Clinical isolates [typed by multi-locus sequence typing (MLST)] and epidemiological data were collected from Scotland. Young rural children were found to have an increased burden of disease in the late spring due to strains of non-chicken origin (e.g. ruminant and wild bird strains from environmental sources). In contrast the adult population had an extended summer peak associated with chicken strains. Travel abroad and UK mainland travel were associated with up to 17% and 18% of cases, respectively. International strains were associated with chicken, had a higher diversity than indigenous strains and a different spectrum of MLST types representative of these countries. Integrating empirical epidemiology and molecular subtyping can successfully elucidate the seasonal components of human campylobacteriosis. The findings will enable public health officials to focus strategies to reduce the disease burden. PMID:22989449

  16. Peştera cu Oase 2 and the cranial morphology of early modern Europeans

    PubMed Central

    Rougier, Hélène; Milota, Ştefan; Rodrigo, Ricardo; Gherase, Mircea; Sarcinǎ, Laurenţiu; Moldovan, Oana; Zilhão, João; Constantin, Silviu; Franciscus, Robert G.; Zollikofer, Christoph P. E.; Ponce de León, Marcia; Trinkaus, Erik

    2007-01-01

    Between 2003 and 2005, the Peştera cu Oase, Romania yielded a largely complete early modern human cranium, Oase 2, scattered on the surface of a Late Pleistocene hydraulically displaced bone bed containing principally the remains of Ursus spelaeus. Multiple lines of evidence indicate an age of ≈40.5 thousand calendar years before the present (≈35 ka 14C B.P.). Morphological comparison of the adolescent Oase 2 cranium to relevant Late Pleistocene human samples documents a suite of derived modern human and/or non-Neandertal features, including absence of a supraorbital torus, subrectangular orbits, prominent canine fossae, narrow nasal aperture, level nasal floor, angled and anteriorly oriented zygomatic bones, a high neurocranium with prominent parietal bosses and marked sagittal parietal curvature, superiorly positioned temporal zygomatic root, vertical auditory porous, laterally bulbous mastoid processes, superiorly positioned posterior semicircular canal, absence of a nuchal torus and a suprainiac fossa, and a small occipital bun. However, these features are associated with an exceptionally flat frontal arc, a moderately large juxtamastoid eminence, extremely large molars that become progressively larger distally, complex occlusal morphology of the upper third molar, and relatively anteriorly positioned zygomatic arches. Moreover, the featureless occipital region and small mastoid process are at variance with the large facial skeleton and dentition. This unusual mosaic in Oase 2, some of which is paralleled in the Oase 1 mandible, indicates both complex population dynamics as modern humans dispersed into Europe and significant ongoing human evolution once modern humans were established within Europe. PMID:17227863

  17. Origins of human cooperation and morality.

    PubMed

    Tomasello, Michael; Vaish, Amrisha

    2013-01-01

    From an evolutionary perspective, morality is a form of cooperation. Cooperation requires individuals either to suppress their own self-interest or to equate it with that of others. We review recent research on the origins of human morality, both phylogenetic (research with apes) and ontogenetic (research with children). For both time frames we propose a two-step sequence: first a second-personal morality in which individuals are sympathetic or fair to particular others, and second an agent-neutral morality in which individuals follow and enforce group-wide social norms. Human morality arose evolutionarily as a set of skills and motives for cooperating with others, and the ontogeny of these skills and motives unfolds in part naturally and in part as a result of sociocultural contexts and interactions. PMID:22804772

  18. Curiosity, forbidden knowledge, and the reformation of natural philosophy in early modern England.

    PubMed

    Harrison, P

    2001-06-01

    From the patristic period to the beginning of the seventeenth century curiosity was regarded as an intellectual vice. Curious individuals were considered to be proud and "puffed up," and the objects of their investigations were deemed illicit, dispute engendering, unknowable, or useless. Seventeenth-century projects for the advancement of learning had to distance themselves from curiosity and its dubious fruits or, alternatively, enhance the moral status of the curious sensibility. Francis Bacon's proposals for the instauration of knowledge were an integral part of a process by which curiosity underwent a remarkable transformation from vice to virtue over the course of the seventeenth century. The changing fortunes of this human propensity highlight the morally charged nature of early modern debates over the status of natural philosophy and the particular virtues required of its practitioners. The rehabilitation of curiosity was a crucial element in the objectification of scientific knowledge and led to a gradual shift of focus away from the moral qualities of investigators and the propriety of particular objects of knowledge to specific procedures and methods. PMID:11590893

  19. Cranial vault trauma and selective mortality in medieval to early modern Denmark

    PubMed Central

    Boldsen, Jesper L.; Milner, George R.; Weise, Svenja

    2015-01-01

    To date, no estimates of the long-term effect of cranial vault fractures on the risk of dying have been generated from historical or prehistoric skeletons. Excess mortality provides a perspective on the efficacy of modern treatment, as well as the human cost of cranial injuries largely related to interpersonal violence in past populations. Three medieval to early modern Danish skeletal samples are used to estimate the effect of selective mortality on males with cranial vault injuries who survived long enough for bones to heal. The risk of dying for these men was 6.2 times higher than it was for their uninjured counterparts, estimated through a simulation study based on skeletal observations. That is about twice the increased risk of dying experienced by modern people with traumatic brain injuries. The mortality data indicate the initial trauma was probably often accompanied by brain injury. Although the latter cannot be directly observed in skeletal remains, it can be inferred through the relative risks of dying. The ability to identify the effects of selective mortality in this skeletal sample indicates it must be taken into account in paleopathological research. The problem is analogous to extrapolating from death register data to modern communities, so epidemiological studies based on mortality data have the same inherent possibility of biases as analyses of ancient skeletons. PMID:25624493

  20. Cranial vault trauma and selective mortality in medieval to early modern Denmark.

    PubMed

    Boldsen, Jesper L; Milner, George R; Weise, Svenja

    2015-02-10

    To date, no estimates of the long-term effect of cranial vault fractures on the risk of dying have been generated from historical or prehistoric skeletons. Excess mortality provides a perspective on the efficacy of modern treatment, as well as the human cost of cranial injuries largely related to interpersonal violence in past populations. Three medieval to early modern Danish skeletal samples are used to estimate the effect of selective mortality on males with cranial vault injuries who survived long enough for bones to heal. The risk of dying for these men was 6.2 times higher than it was for their uninjured counterparts, estimated through a simulation study based on skeletal observations. That is about twice the increased risk of dying experienced by modern people with traumatic brain injuries. The mortality data indicate the initial trauma was probably often accompanied by brain injury. Although the latter cannot be directly observed in skeletal remains, it can be inferred through the relative risks of dying. The ability to identify the effects of selective mortality in this skeletal sample indicates it must be taken into account in paleopathological research. The problem is analogous to extrapolating from death register data to modern communities, so epidemiological studies based on mortality data have the same inherent possibility of biases as analyses of ancient skeletons. PMID:25624493

  1. Primate origins, human origins, and the end of higher taxa.

    PubMed

    Cartmill, Matt

    2012-11-01

    When people learn that I study human evolution and we start talking about it, they sometimes ask me, "How long ago did the first humans live?" My answer is usually another question: "What do you mean by 'humans'?" That response seems as baffling and wrong-headed to them as their question seems to me, and it usually takes us a while to straighten things out. © 2012 Wiley Periodicals, Inc. PMID:23280918

  2. Origin and differentiation of human mitochondrial DNA.

    PubMed Central

    Excoffier, L; Langaney, A

    1989-01-01

    A recent study of mitochondrial DNA (mtDNA) polymorphism has generated much debate about modern human origins by proposing the existence of an "African Eve" living 200,000 years ago somewhere in Africa. In an attempt to synthesize information concerning human mtDNA genetic polymorphism, all available data on mtDNA RFLP have been gathered. A phylogeny of the mtDNA types found in 10 populations reveals that all types could have issued from a single common ancestral type. The distribution of shared types between continental groups indicates that caucasoid populations could be the closest to an ancestral population from which all other continental groups would have diverged. A partial phylogeny of the types found in five other populations also demonstrates that the myth of an African Eden was based on an incorrect "genealogical tree" of mtDNA types. Two measures of molecular diversity have been computed on all samples on the basis of mtDNA type frequencies, on one hand, and on the basis of the number of polymorphic sites in the samples, on the other. A large discrepancy is found between the two measures except in African populations; this suggests the existence of some differential selective mechanisms. The lapse of time necessary for creating the observed molecular diversity from an ancestral monomorphic population has been calculated and is found generally greater in Oriental and caucasoid populations. Implications concerning human mtDNA evolution are discussed. PMID:2562823

  3. The role of western Asia in modern human origins.

    PubMed

    Bar-Yosef, O

    1992-08-29

    Western Asia provides the best collection of human skeletal remains relevant to the two basic models for the emergence of modern humans, namely the 'rapid replacement' and the 'regional continuity' models. Regardless of the taxonomies of particular hominids, their chronology is of crucial importance. Thermoluminescence (TL) and electron spin resonance (ESR) dates demonstrate that the Acheulo-Yabrudian and Mousterian entities and their associated fossils (Zuttiyeh, Tabun, Skhul, Qafzeh, Kebara, Shanidar, Amud) span the late Middle and Upper Pleistocene period. These new dates initiated major chronological revisions and renewed discussion of the cultural-archaeological implications. One of the most important conclusions is that the Middle to Upper Palaeolithic transition (or Revolution) 45-40 ka ago has nothing to do with the appearance of anatomically early modern humans in western Asia, which occurred some 100 ka ago or more. The Levant, the coastal region of the eastern Mediterranean, was both a corridor for movement of humans and animals as well as a refugium during climatically harsh periods. The mixture of morphological characteristics among the available Middle Palaeolithic human fossils is interpreted as reflecting the presence of immigrant and local populations. Archaeologically observable behavioural changes are taken as hints to the pre-adaptations of the Middle to Upper Palaeolithic revolution. The archaeological record of western Asia can contribute significantly to explaining the Middle to Upper Palaeolithic revolution. This region was the core area where the 'Neolithic Revolution' took place. The shift to systematic cultivation and the domestication of animals occurred within a short time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1357694

  4. Understanding the origins of human cancer

    SciTech Connect

    Alexandrov, L. B.

    2015-12-04

    All cancers originate from a single cell that starts to behave abnormally, to divide uncontrollably, and, eventually, to invade adjacent tissues (1). The aberrant behavior of this single cell is due to somatic mutations—changes in the genomic DNA produced by the activity of different mutational processes (1). These various mutational processes include exposure to exogenous or endogenous mutagens, abnormal DNA editing, the incomplete fidelity of DNA polymerases, and failure of DNA repair mechanisms (2). Early studies that sequenced TP53, the most commonly mutated gene in human cancer, provided evidence that mutational processes leave distinct imprints of somatic mutations on the genome of a cancer cell (3). For example, C:G>A:T transversions predominate in smoking-associated lung cancer, whereas C:G>T:A transitions occurring mainly at dipyrimidines and CC:GG>TT:AA double-nucleotide substitutions are common in ultraviolet light–associated skin cancers. Moreover, these patterns of mutations matched the ones induced experimentally by tobacco mutagens and ultraviolet light, respectively, the major, known, exogenous carcinogenic influences in these cancer types, and demonstrated that examining patterns of mutations in cancer genomes can yield information about the mutational processes that cause human cancer (4).

  5. Understanding the origins of human cancer

    DOE PAGESBeta

    Alexandrov, L. B.

    2015-12-04

    All cancers originate from a single cell that starts to behave abnormally, to divide uncontrollably, and, eventually, to invade adjacent tissues (1). The aberrant behavior of this single cell is due to somatic mutations—changes in the genomic DNA produced by the activity of different mutational processes (1). These various mutational processes include exposure to exogenous or endogenous mutagens, abnormal DNA editing, the incomplete fidelity of DNA polymerases, and failure of DNA repair mechanisms (2). Early studies that sequenced TP53, the most commonly mutated gene in human cancer, provided evidence that mutational processes leave distinct imprints of somatic mutations on themore » genome of a cancer cell (3). For example, C:G>A:T transversions predominate in smoking-associated lung cancer, whereas C:G>T:A transitions occurring mainly at dipyrimidines and CC:GG>TT:AA double-nucleotide substitutions are common in ultraviolet light–associated skin cancers. Moreover, these patterns of mutations matched the ones induced experimentally by tobacco mutagens and ultraviolet light, respectively, the major, known, exogenous carcinogenic influences in these cancer types, and demonstrated that examining patterns of mutations in cancer genomes can yield information about the mutational processes that cause human cancer (4).« less

  6. The origin recognition complex in human diseases

    PubMed Central

    Shen, Zhen

    2013-01-01

    ORC (origin recognition complex) serves as the initiator for the assembly of the pre-RC (pre-replication complex) and the subsequent DNA replication. Together with many of its non-replication functions, ORC is a pivotal regulator of various cellular processes. Notably, a number of reports connect ORC to numerous human diseases, including MGS (Meier–Gorlin syndrome), EBV (Epstein–Barr virus)-infected diseases, American trypanosomiasis and African trypanosomiasis. However, much of the underlying molecular mechanism remains unclear. In those genetic diseases, mutations in ORC alter its function and lead to the dysregulated phenotypes; whereas in some pathogen-induced symptoms, host ORC and archaeal-like ORC are exploited by these organisms to maintain their own genomes. In this review, I provide detailed examples of ORC-related human diseases, and summarize the current findings on how ORC is involved and/or dysregulated. I further discuss how these discoveries can be generalized as model systems, which can then be applied to elucidating other related diseases and revealing potential targets for developing effective therapies. PMID:23662735

  7. Early Modern ET, Reflexive Telescopics, and Their Relevance Today

    NASA Astrophysics Data System (ADS)

    Danielson, Dennis

    The period from the discovery of Tycho's New Star in 1572 to Galileo's "geometrization of astronomical space" in 1610 (and the years following) saw the disintegration of the boundary between the sublunary and superlunary spheres—between the "lower storey" and "upper storey" of the Aristotelian Universe. This establishment of a strong physical affinity between the universe "up there" and the earthly realm "down here" was also complemented by the rise of Copernicanism: for once the Earth was seen as a planet, the other planets could readily be imagined as other Earths. This analogy suggested not only physical but also biological affinities and supported the plausibility of humans' capacity to travel to the Moon and beyond. Robert Burton—given the demise of Aristotle's physics—declared in 1621 that "If the heavens be penetrable … it were not amiss in this aerial progress to make wings and fly up." John Wilkins and Francis Godwin in the 1630s actively imagined creatures in the Moon and human journeys thither. The epic poet John Milton in 1667 hinted that "every star [is] perhaps a world / Of destined habitation." Moreover, space travel was no one-way street: Thomas Traherne in the 1670s imagined a dweller among the stars visiting Earth and remarking on what must be the condition of its inhabitants. In these and other ways, seventeenth-century writers offered serious and impressive speculation about extraterrestrial life and its possible perceptions of Earth. Such speculations remain pertinent to astrobiological theory today. What Hans Blumenberg in the 1970s called "reflexive telescopics"—the examination of Earth from an imagined extraterrestrial viewpoint—is an important counterpart to the search for life "out there." It serves as a reminder of the obvious but profound premise that Earth is part of the cosmos. At a popular level we often continue to speak of "outer space" as if the old "two-storey" picture of the universe still had some residual legitimacy. However, if Galileo, Wilkins, and other devotees of the New Astronomy were right about Earth's being a full participant in "the dance of the stars," then "outer" is a merely relative and parochial term, not a scientific or qualitative one. And it is no trivial claim to assert that the search for intelligent life in the universe has already identified its first specimens.

  8. [Longlived examples. Function and formal principles of historical exempla of old age in the early-modern dietetic literature].

    PubMed

    Schäfer, Daniel

    2003-01-01

    Since antiquity, the exemplum can be proven in numerous types of texts, as it fulfills a notable didactic and rhetorical function: On the one hand it serves to a deductive illustration of common doctrines; on the other it is until the Enlightenment the scientific basis of cognition: in the view of medieval artistotelists, of who FRANCIS BACON was (in a special sense) one of the last champions, the exemplum takes on an inductive function: the sensual perception of the exampla generates the understanding of the universal, as the exemplum always refers to the exemplar, to the original form. Regarding the eminent deductive/inductive significance of the exempla, it is not surprising that they are an essential factor in dietetic literature. Whereas such exemples were very rare in the general literature on health care written by physicians and in specific papers of old-age assistance, they formed an integral part of texts composed for a large public by medical laymen such as (Ps.-) ROGER BACON, MARSILIO FICINO, ALVISE CORNARO or FRANCIS BACON. In these studies, the issue of a natural limit of human life was discussed intensively. In this context the "historical" sources were of high importance, even if, from a todays point of view, their use was completely non-historical. Often their crude instrumentalization and new interpretations can only be understood in the scholarly context of the time: E.g. in debates of specialists with outsiders or when serving as argument for physiological theories and therapeutical regimes. Not until late Renaissance, the historical exemple was replaced by the individual experience. It is striking that most of all historical exemples found in dietetic papers were positive. This humanistic and Christian ideal concept of old age, which completely contradicts the medical reality, had obviously a stronger fascination on the authors of early modern times than the inductive function of negative exempla (which are very important for a rational reasoning). Besides the scientific exemple, it is the idealizing one which, in the dietetic texts, gradually assumes the moral function of not discouraging the often aged readers, but of encouraging them to a constructive way of living. PMID:15641198

  9. [Academy idea and Curiositas as leitmotif of the early modern Leopoldina].

    PubMed

    Boehm, Laetitia

    2008-01-01

    Founded in 1652, the Academia Naturae Curiosorum fiercely defended this name, which it wished to bear. On the occasion of the founder's 400th birthday, this article will try to examine the objectives of the concept of academia and the understanding of curiositas in its historical context, with a focus on the early history of the academy up to its receipt of imperial privilege in 1687/88. This is done in four chapters (I-IV). The memorial occasion suggests a preliminary note on our contemporary situation: I. The Jubilee Triangle--Berlin (Berlin academies), Halle-Wittenberg (university), Schweinfurt-Halle (Leopoldina)--considering the fate of the different historical models of scholarly organizations before and after the political turnaround (die "Wende") in 1989/90. The main questions about the 17th century orient themselves around the founding documents, the imperial status of the foundational city, as well as the Bausch family's places of study, educational travels, and library.--II. The Imperially Privileged Leopoldina--"Academy" or "Society"? This question's point of departure is the incipient engagement--the year after J. L. Bausch died (1665)--of G. W. Leibniz, who had likewise earned his doctorate at the University of Altdorf. He was engaged for his state-based vision of society that considered scholarly critique of hitherto extant academies, including the curiosité of the Collegium Medicorum. The summing up of the naturae-curiosi's pursuit of imperial privilege emphasizes the denominational controversy, which pitted the imperial counsellors against the societal Nomen preferred by Vienna. The attempt to interpret both sides of the argument deals on the one hand with the semantic expansion to universities of the concept of academia, inspired by humanism and the reception of Roman law; this expansion also affected the imperial reservation rights (exemplary references to legal argumentation from the work on imperial publicity by Ch. Besold). On the other hand, it deals with aspects of privilege law, regarding the development of new kinds of higher learning institutions and university politics in the imperial city in the confessional era ("Semi-Universities"/"Academies" Strassburg, Nuremberg-Altdorf). This is followed by a thematic balancing.--Chapter III. Curiositas as an Early Modern Leitmotif of Natural Science Academies refers first to the multivalent popular usage of the fashionable and borrowed German word "Kuriosität" [curiosity] during the Enlightenment, then inquires about the word's original definitions in ancient and medieval scholarly traditions. In the age of humanist source study and expeditions into "new worlds", the concept of curiositas as an (ethically ambivalent) "desire for knowledge" was revitalized; this is exemplified by two types of sources: the report of the Orient and Brazil explorer André Thevet and the literarily virulent figure (around 1600) of knowledge-thirsty Faust. A reexamination of the academy's foundational documents, in conjunction with the peregrinatio academica of Schweinfurt doctors to Italy, confirms the old question, now newly posed, about the methodological and programmatic signal of the curiositas device. The self-reflection of the naturae-curiosi and their focus on observational development and natural-historical classifications in the area of "materia medica" show--besides other advances in scholarship in the early 17th century--clear correlation with the "phenomenology of modern thought" that is so often discussed today. However, there must be an evolutionary and innovative differentiation from what would later be called "natural science" disciplines (like biology, zoology, mineralogy, chemistry), as opposed to an all-inclusively defined "scientific revolution", which pertains to astronomical and mathematical ways of thinking, as well as new insights in the physical-instrumental field.--Chapter IV. The Urban Medical Profession Between Scholarly Medicine and Practice applies to the life of the academy's founders as urban physici with supervisional functions determined by their classification into the profession's historical three-part organization of medical personell, and into the forms of "public" health care; here, upper German imperial cities had been influenced by Italian city-states concerning trade relations and printing. Exemplary emphasis is given to developments in Nuremberg (Collegium Medicum and Collegium Pharmaceuticum 1632, medicinal organization 1652) in consideration of the professional circumstances of doctors and pharmacists. Thanks to their educational travels through Italy or The Netherlands, the Bausch's, both father and sons, were able to gain important experience for their future professional practice. These included impressions not only of the academic movement, but also of the networks of museum-like cabinets, anatomical theaters and botanical gardens associated with universities and pharmacies. A concluding look touches on the status of doctors and pharmacists--two traditionally separate healing professions that were nonetheless jointly responsible for the health of their patients--in the religious horizon of the confessional era. PMID:20617610

  10. A Step towards Clerical Preferment: Secondary School Teachers' Careers in Early Modern Sweden

    ERIC Educational Resources Information Center

    Lindmark, Daniel

    2004-01-01

    This article investigates the function served by embarking on a teaching career in the Latin school system for recruitment to the clergy in early modern Sweden. The study is restricted to the eighty-nine teachers serving at Pitea Grammar School in Northern Sweden in the period from 1650 to 1849. The investigation pays considerable attention to the…

  11. Alchemical poetry in medieval and early modern Europe: a preliminary survey and synthesis. Part II - Synthesis.

    PubMed

    Kahn, Didier

    2011-03-01

    This article provides a preliminary description of medieval and early modern alchemical poetry composed in Latin and in the principal vernacular languages of western Europe. It aims to distinguish the various genres in which this poetry flourished, and to identify the most representative aspects of each cultural epoch by considering the medieval and early modern periods in turn. Such a distinction (always somewhat artificial) between two broad historical periods may be justified by the appearance of new cultural phenomena that profoundly modified the character of early modern alchemical poetry: the ever-increasing importance of the prisca theologia, the alchemical interpretation of ancient mythology, and the rise of neo-Latin humanist poetry. Although early modern alchemy was marked by the appearance of new doctrines (notably the alchemical spiritus mundi and Paracelsianism), alchemical poetry was only superficially modified by criteria of a scientific nature, which therefore appear to be of lesser importance. This study falls into two parts. Part I provides a descriptive survey of extant poetry, and in Part II the results of the survey are analysed in order to highlight such distinctive features as the function of alchemical poetry, the influence of the book market on its evolution, its doctrinal content, and the question of whether any theory of alchemical poetry ever emerged. Part II is accompanied by an index of the authors and works cited in both parts. PMID:21797075

  12. A Step towards Clerical Preferment: Secondary School Teachers' Careers in Early Modern Sweden

    ERIC Educational Resources Information Center

    Lindmark, Daniel

    2004-01-01

    This article investigates the function served by embarking on a teaching career in the Latin school system for recruitment to the clergy in early modern Sweden. The study is restricted to the eighty-nine teachers serving at Pitea Grammar School in Northern Sweden in the period from 1650 to 1849. The investigation pays considerable attention to the

  13. The Rhetoric of Bonds, Alliances, and Identities: Interrogating Social Networks in Early Modern English Drama

    ERIC Educational Resources Information Center

    Cady, Christina J.

    2010-01-01

    The household and family have received considerable interest in studies of early modern English drama, but less attention has been paid to how writers represent intimate affective bonds on the stage. Emotion is intangible; yet many writers convincingly convey the intensity of emotional bonds through rhetoric. Rhetoric is a mainstay in…

  14. Elementary Education and the Practices of Literacy in Catholic Girls' Schools in Early Modern Germany

    ERIC Educational Resources Information Center

    Rutz, Andreas

    2012-01-01

    Girls' schools in the early modern era were largely run by nuns and can therefore be distinguished as Catholic institutions of learning. These schools flourished in the Catholic parts of Europe since the turn of the seventeenth century. Despite their focus on religious education, elementary skills such as reading, writing and sometimes arithmetic…

  15. Elementary Education and the Practices of Literacy in Catholic Girls' Schools in Early Modern Germany

    ERIC Educational Resources Information Center

    Rutz, Andreas

    2012-01-01

    Girls' schools in the early modern era were largely run by nuns and can therefore be distinguished as Catholic institutions of learning. These schools flourished in the Catholic parts of Europe since the turn of the seventeenth century. Despite their focus on religious education, elementary skills such as reading, writing and sometimes arithmetic

  16. Teaching the Past in the Early Modern Era: Two Different Ways to Make Use of History

    ERIC Educational Resources Information Center

    Bruter, Annie

    2012-01-01

    Were teachers, of the early modern era not longing for the present? Most colleges of that time did not offer a history course. Still, they did teach a lot about the past since the teaching consisted in the reading of the works of ancient writers. This is because ancient science and literature were considered much more advanced than the science and…

  17. From Apprentice to Master: Social Disciplining and Surgical Education in Early Modern London, 1570-1640

    ERIC Educational Resources Information Center

    Chamberland, Celeste

    2013-01-01

    Due to its ascendancy as the administrative and commercial center of early modern England, London experienced sustained growth in the latter half of the sixteenth century, as waves of rural immigrants sought to enhance their material conditions by tapping into the city's bustling occupational and civic networks. The resultant crowded urban

  18. Teaching Petrarchan and Anti-Petrarchan Discourses in Early Modern English Lyrics

    ERIC Educational Resources Information Center

    Ribes, Purificación

    2012-01-01

    The aim of the present article is to help students realize that Petrarchism has been an influential source of inspiration for Early Modern English lyrics. Its topics and conventions have lent themselves to a wide variety of appropriations which the present selection of texts for analysis tries to illustrate. A few telling examples from Spenser,…

  19. School Jailhouse: Discipline, Space and the Materiality of School Morale in Early-Modern Sweden

    ERIC Educational Resources Information Center

    Norlin, Björn

    2016-01-01

    This paper uses a specific phenomenon of early-modern education in Sweden, the school jail, as a point of departure for a broader analysis of educational policy in the areas of discipline and moral instruction. The paper demonstrates how the jail evolved as a part of a wider network of objects, pedagogical technologies and social routines in this…

  20. The Commerce of Utility: Teaching Mathematical Geography in Early Modern England

    ERIC Educational Resources Information Center

    Cormack, Lesley B.

    2006-01-01

    The teaching and learning of geographical and mathematical knowledge in early modern England was a complex interaction among scholars, practitioners, merchants, and gentry. Each group had different values and goals associated with geographical knowledge and therefore different educational venues and different topics to be investigated. This paper…

  1. A Fruitful Exchange/Conflict: Engineers and Mathematicians in Early Modern Italy

    ERIC Educational Resources Information Center

    Maffioli, Cesare S.

    2013-01-01

    Exchanges of learning and controversies between engineers and mathematicians were important factors in the development of early modern science. This theme is discussed by focusing, first, on architectural and mathematical dynamism in mid 16th-century Milan. While some engineers-architects referred to Euclid and Vitruvius for improving their…

  2. From Apprentice to Master: Social Disciplining and Surgical Education in Early Modern London, 1570-1640

    ERIC Educational Resources Information Center

    Chamberland, Celeste

    2013-01-01

    Due to its ascendancy as the administrative and commercial center of early modern England, London experienced sustained growth in the latter half of the sixteenth century, as waves of rural immigrants sought to enhance their material conditions by tapping into the city's bustling occupational and civic networks. The resultant crowded urban…

  3. A Fruitful Exchange/Conflict: Engineers and Mathematicians in Early Modern Italy

    ERIC Educational Resources Information Center

    Maffioli, Cesare S.

    2013-01-01

    Exchanges of learning and controversies between engineers and mathematicians were important factors in the development of early modern science. This theme is discussed by focusing, first, on architectural and mathematical dynamism in mid 16th-century Milan. While some engineers-architects referred to Euclid and Vitruvius for improving their

  4. Trading secrets: Jews and the early modern quest for clandestine knowledge.

    PubMed

    Jütte, Daniel

    2012-12-01

    This essay explores the significance and function of secrecy and secret sciences in Jewish-Christian relations and in Jewish culture in the early modern period. It shows how the trade in clandestine knowledge and the practice of secret sciences became a complex, sometimes hazardous space for contact between Jews and Christians. By examining this trade, the essay clarifies the role of secrecy in the early modern marketplace of knowledge. The attribution of secretiveness to Jews was a widespread topos in early modern European thought. However, relatively little is known about the implications of such beliefs in science or in daily life. The essay pays special attention to the fact that trade in secret knowledge frequently offered Jews a path to the center of power, especially at court. Furthermore, it becomes clear that the practice of secret sciences, the trade in clandestine knowledge, and a mercantile agenda were often inextricably interwoven. Special attention is paid to the Italian-Jewish alchemist, engineer, and entrepreneur Abramo Colorni (ca. 1544-1599), whose career illustrates the opportunities provided by the marketplace of secrets at that time. Much scholarly (and less scholarly) attention has been devoted to whether and what Jews "contributed" to what is commonly called the "Scientific Revolution." This essay argues that the question is misdirected and that, instead, we should pay more attention to the distinctive opportunities offered by the early modern economy of secrecy. PMID:23488236

  5. The origin and diversity of human retroviruses

    PubMed Central

    Peeters, Martine; DArc, Mirela; Delaporte, Eric

    2014-01-01

    Simian immunodeficiency viruses (SIV), T-cell lymphotrophic viruses (STLV), and foamy viruses (SFV) from non-human primates (NHP) have crossed the species barrier to humans at several occasions, leading to the HIV and HTLV epidemic and to sporadic cases of human infections with simian foamy viruses, respectively. Efficient infection and spread in humans differs between SFV, STLV and SIV, but seems also to differ among the different viruses from the same simian lineage, as illustrated by the different spread of HIV-1 M, N O, P or for the different HIV-2 groups. Among the four HIV-1 groups, only HIV-1 group M has spread worldwide and the actual diversity within HIV-1 M (subtypes, Circulating Recombinants) is the result of subsequent evolution and spread in the human population. HIV-2 did only spread to some extent in West Africa, and similarly as for HIV-1, the nine HIV-2 groups have also a different epidemic spread. Four types of HTLV, type 1 to 4, have been described in humans and for 3 of them simian counterparts (STLV-1, STLV-2, STLV-3) have been identified in multiple NHP species. The majority of human infections are with HTLV-1 which is present throughout the world as clusters of high endemicity. Humans are susceptible to a wide variety of SFVs and seem to acquire these viruses more readily than SIVs or STLVs but no signs of disease in humans nor human-to-human transmission of SFV has been documented yet. The current HIV-1 M epidemic illustrates the impact of a single cross-species transmission. The recent discovery of HIV-1 P, HIV-2 I, new HTLV-1 and HTLV-3 variants as well as SFV infections in humans in Central Africa, show that our knowledge of genetic diversity and cross-species transmissions of simian retroviruses are still incomplete. PMID:24584106

  6. Nero and the last stalk of Silphion: collecting extinct nature in early modern Europe.

    PubMed

    Keller, Vera

    2014-01-01

    Many studies of early modern natural history focus upon observational, empirical techniques. Early moderns also contended with entities which could no longer be observed because they no longer existed. Although it is often assumed that extinction only emerged as a concept in the eighteenth century, the concept of natural loss appeared, often unproblematically, in areas outside natural philosophy. A survey of discussions of the extinct plant silphion across Europe in the sixteenth and seventeenth centuries shows that the possibility of natural loss was well aired. Paper technologies for collecting extinct nature ran parallel to investigations of newly found nature, and thus can place the latter in a new light. Although ideas of natural mutability often drew on ideas of historical or political change rather than philosophical concepts of natural constancy, techniques developed for extinct nature, such as the list of lost things, remained influential for the research agendas of naturalists. PMID:25581992

  7. Juan Ruiz De Alarcón: Impairment as Empowerment in Early Modern Spain

    ERIC Educational Resources Information Center

    Clark, Gloria Bodtorf

    2016-01-01

    Juan Ruiz de Alarcón, a seventeenth-century writer and native of New Spain, so excelled at the craft of writing "comedias" that he is recognized as one of the great writers of early modern Spain. In his personal life Ruiz de Alarcón struggled with a significant bodily impairment, a large hump on both his back and front, which made him…

  8. Collecting Knowledge for the Family: Recipes, Gender and Practical Knowledge in the Early Modern English Household

    PubMed Central

    Leong, Elaine

    2013-01-01

    When Mary Cholmeley married Henry Fairfax in 1627, she carried to her new home in Yorkshire a leather-bound notebook filled with medical recipes. Over the next few decades, Mary and Henry, their children and various members of the Fairfax and Cholmeley families continually entered new medical and culinary information into this ‘treasury for health.’ Consequently, as it stands now, the manuscript can be read both as a repository of household medical knowledge and as a family archive. Focusing on two Fairfax ‘family books,’ this essay traces on the process through which early modern recipe books were created. In particular, it explores the role of the family collective in compiling books of knowledge. In contrast to past studies where household recipe books have largely been described as the products of exclusively female endeavors, I argue that the majority of early modern recipe collections were created by family collectives and that the members of these collectives worked in collaboration across spatial, geographical and temporal boundaries. This new reading of recipe books as testaments of the interests and needs of particular families encourages renewed examination of the role played by gender in the transmission and production of knowledge in early modern households. PMID:23926360

  9. Collecting Knowledge for the Family: Recipes, Gender and Practical Knowledge in the Early Modern English Household.

    PubMed

    Leong, Elaine

    2013-05-01

    When Mary Cholmeley married Henry Fairfax in 1627, she carried to her new home in Yorkshire a leather-bound notebook filled with medical recipes. Over the next few decades, Mary and Henry, their children and various members of the Fairfax and Cholmeley families continually entered new medical and culinary information into this 'treasury for health.' Consequently, as it stands now, the manuscript can be read both as a repository of household medical knowledge and as a family archive. Focusing on two Fairfax 'family books,' this essay traces on the process through which early modern recipe books were created. In particular, it explores the role of the family collective in compiling books of knowledge. In contrast to past studies where household recipe books have largely been described as the products of exclusively female endeavors, I argue that the majority of early modern recipe collections were created by family collectives and that the members of these collectives worked in collaboration across spatial, geographical and temporal boundaries. This new reading of recipe books as testaments of the interests and needs of particular families encourages renewed examination of the role played by gender in the transmission and production of knowledge in early modern households. PMID:23926360

  10. Human Behaviour and the Origin of Man

    ERIC Educational Resources Information Center

    Raleigh, M. J.; Washburn, S. L.

    1973-01-01

    The study of origin and evolution of man gives new perspective for understanding his behavior. Physical behaviors such as walking and throwing are results of biological evolution which has not kept pace with sociocultural evolution. Irrational decisions by man in social, cultural, and political fields are results of this brain activity. (PS)

  11. Origins of the human genome project

    SciTech Connect

    Watson, J.D.; Cook-Deegan, R.M. )

    1991-01-01

    The Human Genome Project has become a reality. Several genome projects are now in full stride around the world, and more are likely to form in the next several years. The purpose of genome projects is to assemble data on the structure of DNA in human chromosomes and those of other organisms. A second goal is to develop new technologies to perform mapping and sequencing. There have been impressive technical advances in the past 5 years. We are on the verge of beginning pilot projects to test several approaches to sequencing long stretches of DNA, using both automation and manual methods. Ordered sets of yeast artificial chromosome and cosmid clones have been assembled to span more than 2 million base pairs of several human chromosomes, and a region of 10 million base pairs has been assembled for Caenorhabditis elegans.

  12. Synergistes Group Organisms of Human Origin

    PubMed Central

    Horz, Hans-Peter; Citron, Diane M.; Warren, Yumi A.; Goldstein, Ellie J. C.; Conrads, Georg

    2006-01-01

    The bacterial division Synergistes represents a poorly characterized phylotype of which only a few isolates have been cultured, primarily from natural environments. Recent detection of Synergistes-like sequence types in periodontal pockets and caries lesions of humans prompted us to search the R. M. Alden culture collection (Santa Monica, Calif.) for biochemically unidentifiable, slow-growing, obligately anaerobic gram-negative bacilli. Here we report on five clinical isolates cultured from peritoneal fluid and two isolates from soft-tissue infections that together constitute three separate evolutionary lineages within the phylogenetic radiation of the division Synergistes. One of these clusters was formed by the peritoneal isolates and had an 85% similarity to Synergistes jonesii, the first described Synergistes species, which was isolated from the rumen of a goat. The isolates from soft-tissue infections, on the other hand, formed two distinct lineages moderately related to each other with a similarity of approximately 78%. In addition, by using a newly designed 16S rRNA gene-based PCR assay with intended target specificity for Synergistes, we found that the dominant phylotype from a fecal sample was nearly identical to that of the strains obtained from peritonitis. Conversely, sequence types detected in periodontal pockets formed a separate cluster that shared a similarity of only 80% with the soft-tissue isolates. These findings suggest a high diversity of medically important Synergistes clades that apparently are unique to individual ecological niches in the human body. In conclusion, we now have available the first characterized human isolates of the division Synergistes which are colonizing, and probably infecting, several sites in the human body. PMID:16891512

  13. On the origin of the human treponematoses

    PubMed Central

    Hackett, C. J.

    1963-01-01

    A close relationship between the four human treponematoses is suggested by their clinical and epidemiological characteristics and by such limited knowledge of the treponemes as there is at present. No treponeme of this group (except for that of the rabbit) is known other than in man, but the human treponemes probably arose long ago from an animal infection. The long period of infectiousness of pinta suggests that it may have been the earliest human treponematosis. It may have been spread throughout the world by about 15 000 B.C., being subsequently isolated in the Americas when the Bering Strait was flooded. About 10 000 B.C. in the Afro-Asian land mass environmental conditions might have favoured treponeme mutants leading to yaws; from these, about 7000 B.C., endemic syphilis perhaps developed, to give rise to venereal syphilis about 3000 B.C. in south-west Asia as big cities developed there. Towards the end of the fifteenth century A.D. a further mutation may have resulted in a more severe venereal syphilis in Europe which, with European exploration and geographical expansion, was subsequently carried throughout the then treponemally uncommitted world. These suggestions find some tentative support in climatic changes which might have influenced the selection of those treponemes which still survive in humid or arid climates. Venereal transmission would presumably remove the treponeme from the direct influence of climate. The author makes a plea for further investigation of many aspects of this subject while this is still possible. PMID:14043755

  14. "None Must Meddle Betueene Man and Wife": assessing family and the fluidity of public and private in early modern Scotland.

    PubMed

    Nugent, Janay

    2010-01-01

    The physical and ideological boundaries between public and private in early modern Scotland were constantly contested, resulting in a shifting reality of what was public and private. This fluidity has been recognized by historians, but how, when, and why the shifting took place is not as clear. The moral church courts (Kirk Sessions) of Reformation Scotland allow a unique opportunity to begin to understand the largely elusive boundaries between public and private in the early modern era. PMID:20715315

  15. All that glitters: fool's gold in the early-modern era.

    PubMed

    Roos, Anna Marie

    2008-12-01

    Natural philosophers of the early-modern period perceived fool's gold or iron pyrites as a substance required for the formation of metals, and chemists such as Johann Glauber speculated the vitriol produced from pyrites was the source of the legendary philosopher's stone. The sulphurous exhalations of fool's gold were also thought by members of the early Royal Society to be the basis of a variety of meteorological, geological and medical effects, including the production of thunder, lightning, earthquakes and volcanoes, fossilisation and petrifaction, as well as the principal cause of bladder and gallstones. PMID:19019438

  16. (See symbol in text) in early modern discussions of the passions: Stoicism, Christianity and natural history.

    PubMed

    Kraye, Jill

    2012-01-01

    This paper examines the reception of the Stoic theory of the passions in the early modern period, highlighting various differences between the way notions such as (see symbol in text) (complete freedom from passions) and(see symbol in text) (pre-passions) were handled and interpreted by Continental and English authors. Both groups were concerned about the compatibility of Stoicism with Christianity, but came to opposing conclusions; and while the Continental scholars drew primarily on ancient philosophical texts, the English ones relied, in addition, on experience and observation, developing a natural history of the passions. PMID:22702173

  17. 'To[o] much eating stifles the child': fat bodies and reproduction in early modern England .

    PubMed

    Toulalan, Sarah

    2014-02-01

    This article examines associations between fat bodies and reproductive dysfunction that were prevalent in medical, midwifery and other literature in early modern England. In a period when fertility and successful reproduction were regarded as hugely important for social, economic and political stability such associations further contributed to negative attitudes towards fat bodies that were fuelled by connection with the vices of sloth and gluttony. Fat bodies were categorized as inherently, constitutionally, less sexual and reproductively successful. Consequently they were perceived as unhealthy and unfit for their primary purpose once they had reached sexual maturity: marriage and the production of children. PMID:25960608

  18. Investigating early modern Ottoman consumer culture in the light of Bursa probate inventories.

    PubMed

    Karababa, Eminegül

    2012-01-01

    This study investigates the development of early modern Ottoman consumer culture. In particular, the democratization of consumption, which is a significant indicator of the development of western consumer cultures, is examined in relation to Ottoman society. Sixteenth- and seventeenth-century probate inventories of the town of Bursa combined with literary and official sources are used in order to identify democratization of consumption and the macro conditions shaping this development. Findings demonstrate that commercialization, international trade, urbanization which created a fluid social structure, and the ability of the state to negotiate with guilds were possible contextual specificities which encouraged the democratization of consumption in the Bursa context. PMID:22329064

  19. Animals inside. Anatomy, interiority and virtue in the early modern Dutch Republic.

    PubMed

    Knoeff, Rina

    2008-01-01

    People in the early modern period frequently gave accounts of little animals (such as worms, flies, slugs and even dogs) living and breeding inside their bodies. This article investigates descriptions of "animals inside" in the works of Dutch anatomist Frederik Ruysch. It links the occurrence of such animals to the fear of pile worms endangering Dutch dikes and houses, and thereby the safety of society. The animals embodied pain and discomfort and were often associated with immorality and sexuality. As powerful symbols of interior corruption, they served as tangible reminders of the corruption of individuals as well as of the nation. PMID:18664011

  20. [Mental interiority in the early-modern age. The "Cartesian theater"].

    PubMed

    Gillot, Pascale

    2010-01-01

    This paper looks into the notion of mental interiority in the early-modern age and, more specifically, into the Cartesian conception of the mind as an "inner theater". The main claim emphasizes a close connexion at work between the representative theory of the mind, associated with internalism, on the one hand, and a "neuropsychological" view on the other hand. Cartesian mentalism, in so far as it is based upon a disjunction between representation and resemblance, can therefore not be separated from the general project, already at work in the Dioptrique, of an intra-cerebral localization of the mental. PMID:20533801

  1. Origins of the Human Genome Project

    SciTech Connect

    Cook-Deegan, Robert

    1993-07-01

    The human genome project was borne of technology, grew into a science bureaucracy in the US and throughout the world, and is now being transformed into a hybrid academic and commercial enterprise. The next phase of the project promises to veer more sharply toward commercial application, harnessing both the technical prowess of molecular biology and the rapidly growing body of knowledge about DNA structure to the pursuit of practical benefits. Faith that the systematic analysis of DNA structure will prove to be a powerful research tool underlies the rationale behind the genome project. The notion that most genetic information is embedded in the sequence of CNA base pairs comprising chromosomes is a central tenet. A rough analogy is to liken an organism's genetic code to computer code. The coal of the genome project, in this parlance, is to identify and catalog 75,000 or more files (genes) in the software that directs construction of a self-modifying and self-replicating system -- a living organism.

  2. Origins of the Human Genome Project

    DOE R&D Accomplishments Database

    Cook-Deegan, Robert (Affiliation: Institute of Medicine, National Academy of Sciences)

    1993-07-01

    The human genome project was borne of technology, grew into a science bureaucracy in the United States and throughout the world, and is now being transformed into a hybrid academic and commercial enterprise. The next phase of the project promises to veer more sharply toward commercial application, harnessing both the technical prowess of molecular biology and the rapidly growing body of knowledge about DNA structure to the pursuit of practical benefits. Faith that the systematic analysis of DNA structure will prove to be a powerful research tool underlies the rationale behind the genome project. The notion that most genetic information is embedded in the sequence of CNA base pairs comprising chromosomes is a central tenet. A rough analogy is to liken an organism's genetic code to computer code. The coal of the genome project, in this parlance, is to identify and catalog 75,000 or more files (genes) in the software that directs construction of a self-modifying and self-replicating system -- a living organism.

  3. ["Lingue di seripi", "serpents' tongues" and "glossopetrae". Highlights from the history of popular "cult" medicine in early modern times].

    PubMed

    Freller, T

    1997-01-01

    In the 16th, 17th and 18th century "Glossopetrae", popularly known as "Lingue di Serpi", found on the Mediterranean island of Malta, were extensively used for medical purposes as antidotes. These fossil teeth, including specimens of the "Carcharodon Megalodon" (an extinct variant of the great white shark), were ground to powder or used as amulet pendants and "credence" and exported to pharmacies and shops in various cities of Europe. In antiquity, authors like Plinius or Solinus, excluding any religious connotations, had regarded "Glossopetrae" as objects "fallen from heaven on dark moonless nights". However, from the beginning of the 16th century the miraculous antidotic power of the specimens found at Malta was very strongly connected with the Pauline cult there. This cult owed ist origin to the excerpt of the shipwreck of the Apostle of the Gentiles on this island, as recorded in the New Testament. As in so many cases found in medieval and early modern medicine and pharmacy, the renown, collection, distribution and use of the antidote "Glossopetrae" or "Lingue di Serpi" was never limited to its real chemical and pharmaceutical properties. In the period of enlightenment and secular thinking mythic medicine as "Glossopetrae" had lost ist "magical" power. Consequently, with beginning of the late 18th century also the Maltese "Glossopetrae" featured in literature merely as exotic objects of curiosity or symbols of an age bound to medical superstition. PMID:9333999

  4. ‘Herbals she peruseth’: reading medicine in early modern England

    PubMed Central

    Leong, Elaine

    2014-01-01

    In 1631, Richard Brathwaite penned a conduct manual for ‘English Gentlewomen’. In Brathwaite's mind, the ideal English gentlewoman was not only chaste, modest and honourable but also an avid reader. In fact, Brathwaite specifically recommends English gentlewomen to first peruse herbals and then to deepen their medical knowledge via conference. Centred on the manuscript notebooks of two late seventeenth-century women, Margaret Boscawen (d. 1688) and Elizabeth Freke (1642–1714), this article explores women and ‘medical reading’ in early modern England. It first demonstrates that whilst both women consulted herbals by contemporary authors such as John Gerard and Nicholas Culpeper, their modes of reading could not be more different. Where Freke ruminated, digested and abstracted from Gerard's large tome, Boscawen made practical lists from Culpeper's The English Physitian. Secondly, the article shows that both supplemented their herbal reading with a range of other vernacular medical texts including printed medical recipe books, contemporary pharmacopoeia and surgical handbooks. Early modern English women's medical reading, I argue, was nuanced, sophisticated and diverse. Furthermore, I contend that well-informed readers like Boscawen and Freke made smart medical consumers and formidable negotiators in their medical encounters. PMID:25821333

  5. The early Upper Paleolithic human skeleton from the Abrigo do Lagar Velho (Portugal) and modern human emergence in Iberia

    PubMed Central

    Duarte, Cidália; Maurício, João; Pettitt, Paul B.; Souto, Pedro; Trinkaus, Erik; van der Plicht, Hans; Zilhão, João

    1999-01-01

    The discovery of an early Upper Paleolithic human burial at the Abrigo do Lagar Velho, Portugal, has provided evidence of early modern humans from southern Iberia. The remains, the largely complete skeleton of a ≈4-year-old child buried with pierced shell and red ochre, is dated to ca. 24,500 years B.P. The cranium, mandible, dentition, and postcrania present a mosaic of European early modern human and Neandertal features. The temporal bone has an intermediate-sized juxtamastoid eminence. The mandibular mentum osseum and the dental size and proportions, supported by mandibular ramal features, radial tuberosity orientation, and diaphyseal curvature, as well as the pubic proportions align the skeleton with early modern humans. Body proportions, reflected in femorotibial lengths and diaphyseal robusticity plus tibial condylar displacement, as well as mandibular symphyseal retreat and thoracohumeral muscle insertions, align the skeleton with the Neandertals. This morphological mosaic indicates admixture between regional Neandertals and early modern humans dispersing into southern Iberia. It establishes the complexities of the Late Pleistocene emergence of modern humans and refutes strict replacement models of modern human origins. PMID:10377462

  6. The early Upper Paleolithic human skeleton from the Abrigo do Lagar Velho (Portugal) and modern human emergence in Iberia.

    PubMed

    Duarte, C; Maurício, J; Pettitt, P B; Souto, P; Trinkaus, E; van der Plicht, H; Zilhão, J

    1999-06-22

    The discovery of an early Upper Paleolithic human burial at the Abrigo do Lagar Velho, Portugal, has provided evidence of early modern humans from southern Iberia. The remains, the largely complete skeleton of a approximately 4-year-old child buried with pierced shell and red ochre, is dated to ca. 24,500 years B.P. The cranium, mandible, dentition, and postcrania present a mosaic of European early modern human and Neandertal features. The temporal bone has an intermediate-sized juxtamastoid eminence. The mandibular mentum osseum and the dental size and proportions, supported by mandibular ramal features, radial tuberosity orientation, and diaphyseal curvature, as well as the pubic proportions align the skeleton with early modern humans. Body proportions, reflected in femorotibial lengths and diaphyseal robusticity plus tibial condylar displacement, as well as mandibular symphyseal retreat and thoracohumeral muscle insertions, align the skeleton with the Neandertals. This morphological mosaic indicates admixture between regional Neandertals and early modern humans dispersing into southern Iberia. It establishes the complexities of the Late Pleistocene emergence of modern humans and refutes strict replacement models of modern human origins. PMID:10377462

  7. Approaches to the History of Patients: From the Ancient World to Early Modern Europe.

    PubMed

    Stolberg, Michael

    2016-01-01

    This chapter looks from an early modernist's perspective at some of the major questions and methodological issues that writing the history of patients in the ancient world shares with similar work on Patientengeschichte in medieval and early modern Europe. It addresses, in particular, the problem of finding adequate sources that give access to the patients' experience of illness and medicine and highlights the potential as well as the limitations of using physicians' case histories for that purpose. It discusses the doctor-patient relationship as it emerges from these sources, and the impact of the patient's point of view on learned medical theory and practice. In conclusion, it pleads for a cautious and nuanced approach to the controversial issue of retrospective diagnosis, recommending that historians consistently ask in which contexts and in what way the application of modern diagnostic labels to pre-modern accounts of illness can truly contribute to a better historical understanding rather than distort it. PMID:26946692

  8. Expanding women's rural medical work in early modern Brittany: the Daughters of the Holy Spirit.

    PubMed

    McHugh, Tim

    2012-07-01

    During the eighteenth century, orders of nursing sisters took on an expanded role in the rural areas of Brittany. This article explores the impact of religious change on the medical activities of these women. While limits were placed on the medical practice of unlicensed individuals, areas of new opportunity for nuns as charitable practitioners were created by devout nobles throughout the eighteenth century. These nuns provided comprehensive care for the sick poor on their patrons' estates, acting not only as nurses, but also in lieu of physicians, surgeons, and apothecaries. This article argues that the medical knowledge and expertise of these sisters from the nursing orders were highly valued by the elites of early modern Brittany. PMID:21724643

  9. Alchemy as studies of life and matter: reconsidering the place of vitalism in early modern chemistry.

    PubMed

    Chang, Ku-ming

    2011-06-01

    Early modern alchemy studied both matter and life, much like today's life sciences. What material life is and how it comes about intrigued alchemists. Many found the answer by assuming a vital principle that served as the source and cause of life. Recent literature has presented important cases in which vitalist formulations incorporated corpuscular or mechanical elements that were characteristic of the New Science and other cases in which vitalist thinking influenced important figures of the Scientific Revolution. Not merely speculative, vitalist ideas also motivated chymical practice. The unity of life science and material science that is found in many formulations of Renaissance alchemy disintegrated in Georg Ernst Stahl's version of post-Cartesian vitalism. PMID:21874692

  10. Expanding Women's Rural Medical Work in Early Modern Brittany: The Daughters of the Holy Spirit

    PubMed Central

    McHugh, Tim

    2012-01-01

    During the eighteenth century, orders of nursing sisters took on an expanded role in the rural areas of Brittany. This article explores the impact of religious change on the medical activities of these women. While limits were placed on the medical practice of unlicensed individuals, areas of new opportunity for nuns as charitable practitioners were created by devout nobles throughout the eighteenth century. These nuns provided comprehensive care for the sick poor on their patrons' estates, acting not only as nurses, but also in lieu of physicians, surgeons, and apothecaries. This article argues that the medical knowledge and expertise of these sisters from the nursing orders were highly valued by the elites of early modern Brittany. PMID:21724643

  11. The origin and distribution of human lice in the world.

    PubMed

    Boutellis, Amina; Abi-Rached, Laurent; Raoult, Didier

    2014-04-01

    Two genera of lice parasitize humans: Pthirus and Pediculus. The latter is of significant public health importance and comprises two ecotypes: the body louse and the head louse. These ecotypes are morphologically and genetically notably similar; the body louse is responsible for three infectious diseases: Louse-borne epidemic typhus, relapsing fever, and trench fever. Mitochondrial DNA studies have shown that there are three obviously divergent clades of head lice (A, B and C), and only one clade of body lice is shared with head lice (clade A). Each clade has a unique geographic distribution. Lice have been parasitizing humans for millions of years and likely dispersed throughout the World with the human migrations out of Africa, so they can be good markers for studying human evolution. Here, we present an overview of the origin of human lice and their role in vector pathogenic bacteria that caused epidemics, and we review the association between lice clades and human migrations. PMID:24524985

  12. Origins of XMRV deciphered, undermining claims for role in humans

    Cancer.gov

    Delineation of the origin of the retrovirus known as XMRV from the genomes of laboratory mice indicates that the virus is unlikely to be responsible for either prostate cancer or chronic fatigue syndrome in humans, as has been widely published. The virus arose because of genetic recombination of two mouse viruses.

  13. "The Root is Hidden and the Material Uncertain": the challenges of prosecuting witchcraft in early modern Venice.

    PubMed

    Seitz, Jonathan

    2009-01-01

    The rich archival records of the Holy Office of the Inquisition in Venice have yielded much information about early modern society and culture. The transcripts of witchcraft trials held before the Inquisition reveal the complexities of early modern conceptions of natural and supernatural. The tribunal found itself entirely unable to convict individuals charged with performing harmful magic, or maleficio, as different worldviews clashed in the courtroom. Physicians, exorcists, and inquisitors all had different approaches to distinguishing natural phenomena from supernatural, and without a consensus guilty verdicts could not be obtained. PMID:19618523

  14. The evolutionary origin of human hyper-cooperation.

    PubMed

    Burkart, J M; Allon, O; Amici, F; Fichtel, C; Finkenwirth, C; Heschl, A; Huber, J; Isler, K; Kosonen, Z K; Martins, E; Meulman, E J; Richiger, R; Rueth, K; Spillmann, B; Wiesendanger, S; van Schaik, C P

    2014-01-01

    Proactive, that is, unsolicited, prosociality is a key component of our hyper-cooperation, which in turn has enabled the emergence of various uniquely human traits, including complex cognition, morality and cumulative culture and technology. However, the evolutionary foundation of the human prosocial sentiment remains poorly understood, largely because primate data from numerous, often incommensurable testing paradigms do not provide an adequate basis for formal tests of the various functional hypotheses. We therefore present the results of standardized prosociality experiments in 24 groups of 15 primate species, including humans. Extensive allomaternal care is by far the best predictor of interspecific variation in proactive prosociality. Proactive prosocial motivations therefore systematically arise whenever selection favours the evolution of cooperative breeding. Because the human data fit this general primate pattern, the adoption of cooperative breeding by our hominin ancestors also provides the most parsimonious explanation for the origin of human hyper-cooperation. PMID:25158760

  15. African origin of human-specific polymorphic Alu insertions

    SciTech Connect

    Batzer, M.A.; Alegria-Hartman, M. ); Stoneking, M. ); Bazan, H.; Kass, D.H.; Shaikh, T.H.; Scheer, W.D. ); Novick, G.E.; Herrera, R.J. ); Ioannou, P.A. )

    1994-12-06

    Alu elements are a family of interspersed repeats that have mobilized throughout primate genomes by retroposition from a few [open quotes]master[close quotes] genes. Among the 500,000 Alu elements in the human genome are members of the human-specific subfamily that are not fixed in the human species. Four such polymorphic human-specific Alu insertions were analyzed by a rapid, PCR-based assay. These four polymorphic Alu insertions were shown to be absent from the genomes of a number of nonhuman primates, consistent with their arising as human genetic polymorphisms sometime after the human/African ape divergence. Analysis of 664 unrelated individuals from 16 population groups from around the world revealed substantial levels of variation within population groups and significant genetic differentiation among groups. No significant associations were found among the four loci, consistent with their location on different chromosomes. A maximum-likelihood tree of population relationships showed four major groupings consisting of Africa, Europe, Asia/Americas, and Australia/New Guinea, which is concordant with similar trees based on other loci. A particularly useful feature of the polymorphic Alu insertions is that the ancestral state is known to be the absence of the Alu element, and the presence of the Alu element at a particular chromosomal site reflects a single, unique event in human evolution. A hypothetical ancestral group can then be included in the tree analysis, with the frequency of each insertion set to zero. The ancestral group connected to the maximum-likelihood tree within the African branch, which suggests an African origin of these polymorphic Alu insertions. These data are concordant with other diverse data sets, which lends further support to the recent African origin hypothesis for modern humans. Polymorphic Alu insertions represent a source of genetic variation for studying human population structure and evolution. 45 refs., 2 figs., 1 tab.

  16. Trapping DNA Replication Origins from the Human Genome

    PubMed Central

    Eki, Toshihiko; Murakami, Yasufumi; Hanaoka, Fumio

    2013-01-01

    Synthesis of chromosomal DNA is initiated from multiple origins of replication in higher eukaryotes; however, little is known about these origins’ structures. We isolated the origin-derived nascent DNAs from a human repair-deficient cell line by blocking the replication forks near the origins using two different origin-trapping methods (i.e., UV- or chemical crosslinker-treatment and cell synchronization in early S phase using DNA replication inhibitors). Single-stranded DNAs (of 0.5–3 kb) that accumulated after such treatments were labeled with bromodeoxyuridine (BrdU). BrdU-labeled DNA was immunopurified after fractionation by alkaline sucrose density gradient centrifugation and cloned by complementary-strand synthesis and PCR amplification. Competitive PCR revealed an increased abundance of DNA derived from known replication origins (c-myc and lamin B2 genes) in the nascent DNA fractions from the UV-treated or crosslinked cells. Nucleotide sequences of 85 and 208 kb were obtained from the two libraries (I and II) prepared from the UV-treated log-phase cells and early S phase arrested cells, respectively. The libraries differed from each other in their G+C composition and replication-related motif contents, suggesting that differences existed between the origin fragments isolated by the two different origin-trapping methods. The replication activities for seven out of 12 putative origin loci from the early-S phase cells were shown by competitive PCR. We mapped 117 (library I) and 172 (library II) putative origin loci to the human genome; approximately 60% and 50% of these loci were assigned to the G-band and intragenic regions, respectively. Analyses of the flanking sequences of the mapped loci suggested that the putative origin loci tended to associate with genes (including conserved sites) and DNase I hypersensitive sites; however, poor correlations were found between such loci and the CpG islands, transcription start sites, and K27-acetylated histone H3 peaks. PMID:24705160

  17. Alchemical poetry in medieval and early modern Europe: a preliminary survey and synthesis. Part I--Preliminary survey.

    PubMed

    Kahn, Didier

    2010-11-01

    This article provides a preliminary description of medieval and early modern alchemical poetry composed in Latin and in the principal vernacular languages of western Europe. It aims to distinguish the various genres in which this poetry flourished, and to identify the most representative aspects of each cultural epoch by considering the medieval and early modern periods in turn. Such a distinction (always somewhat artificial) between two broad historical periods may be justified by the appearance of new cultural phenomena that profoundly modified the character of early modern alchemical poetry: the ever-increasing importance of the prisca theologia, the alchemical interpretation of ancient mythology, and the rise of neo-Latin humanist poetry. Although early modern alchemy was marked by the appearance of new doctrines (notably the alchemical spiritus mundi and Paracelsianism), alchemical poetry was only superficially modified by criteria of a scientific nature, which therefore appear to be of lesser importance. This study falls into two parts. Part I provides a descriptive survey of extant poetry, and in Part II the results of the survey are analysed in order to highlight such distinctive features as the function of alchemical poetry, the influence of the book market on its evolution, its doctrinal content, and the question of whether any theory of alchemical poetry ever emerged. Part II is accompanied by an index of the authors and works cited in both parts. PMID:21465995

  18. Origin of the styloglossus muscle in the human fetus

    PubMed Central

    Mrida-Velasco, J R; Rodrguez-Vazquez, J F; de la Cuadra Blanco, C; Snchez-Montesinos, I; Mrida-Velasco, J A

    2006-01-01

    The origin of the styloglossus muscle was histologically studied bilaterally in nine human fetuses (18 sides). In all cases, the muscle originated in Reichert's cartilage, which gives rise to the temporal styloid process. We identified three types of variation: type A, an accessory muscle fascicle originating from the mandibular angle, found in 7 cases (12 sides); type B, where the styloglossus muscle was attached to the mandibular angle by fibrous tracts, found in three cases (4 sides); and type C, where an accessory muscle fascicle arose from the fibrous tract connecting Reichert's cartilage to the mandibular angle; found in one case. In all cases (2 sides), the styloglossus muscle was innervated by the hypoglossal nerve. Relationships between the styloglossus muscle and vasculonervous elements of the prestyloid and retrostyloid spaces were analysed. PMID:16637887

  19. Subcortical origins of human and monkey neocortical interneurons.

    PubMed

    Ma, Tong; Wang, Congmin; Wang, Lei; Zhou, Xing; Tian, Miao; Zhang, Qiangqiang; Zhang, Yue; Li, Jiwen; Liu, Zhidong; Cai, Yuqun; Liu, Fang; You, Yan; Chen, Chao; Campbell, Kenneth; Song, Hongjun; Ma, Lan; Rubenstein, John L; Yang, Zhengang

    2013-11-01

    Cortical GABAergic inhibitory interneurons have crucial roles in the development and function of the cerebral cortex. In rodents, nearly all neocortical interneurons are generated from the subcortical ganglionic eminences. In humans and nonhuman primates, however, the developmental origin of neocortical GABAergic interneurons remains unclear. Here we show that the expression patterns of several key transcription factors in the developing primate telencephalon are very similar to those in rodents, delineating the three main subcortical progenitor domains (the medial, lateral and caudal ganglionic eminences) and the interneurons tangentially migrating from them. On the basis of the continuity of Sox6, COUP-TFII and Sp8 transcription factor expression and evidence from cell migration and cell fate analyses, we propose that the majority of primate neocortical GABAergic interneurons originate from ganglionic eminences of the ventral telencephalon. Our findings reveal that the mammalian neocortex shares basic rules for interneuron development, substantially reshaping our understanding of the origin and classification of primate neocortical interneurons. PMID:24097041

  20. Differences and similarities in the regulation of medical practice between early modern Vienna and Osijek.

    PubMed

    Atalic, Bruno

    2012-09-01

    This paper evaluates the regulation of medical practice from the sixteenth to the eighteenth centuries in two Habsburg cities, Vienna and Osijek, in the light of the spread of medical knowledge and practice from the centre to the periphery of the Habsburg Monarchy. Although both cities were part of the Habsburg Monarchy for much of the early modern period, there were more differences than similarities between them. This may be explained by appealing to a variety of factors, including geographical position, population structure, religion, government type, and professional organisations, all of which contributed to making medical practice very different in the two cities. The divergence occurred in spite of a central agenda for ensuring uniformity of medical practice throughout the Habsburg Monarchy. Although the legislation governing medical practice was the same in both cities, it was more strictly implemented in Vienna than in Osijek. In consequence, Osijek was the setting for some unique patterns of medical practice not to be found in the Habsburg capital. PMID:22580020

  1. Training the intelligent eye: understanding illustrations in early modern astronomy texts.

    PubMed

    Crowther, Kathleen M; Barker, Peter

    2013-09-01

    Throughout the early modern period, the most widely read astronomical textbooks were Johannes de Sacrobosco's De sphaera and the Theorica planetarum, ultimately in the new form introduced by Georg Peurbach. This essay argues that the images in these texts were intended to develop an "intelligent eye." Students were trained to transform representations of specific heavenly phenomena into moving mental images of the structure of the cosmos. Only by learning the techniques of mental visualization and manipulation could the student "see" in the mind's eye the structure and motions of the cosmos. While anyone could look up at the heavens, only those who had acquired the intelligent eye could comprehend the divinely created order of the universe. Further, the essay demonstrates that the visual program of the Sphaera and Theorica texts played a significant and hitherto unrecognized role in later scientific work. Copernicus, Galileo, and Kepler all utilized the same types of images in their own texts to explicate their ideas about the cosmos. PMID:24341260

  2. Effects of student ontological position on cognition of human origins

    NASA Astrophysics Data System (ADS)

    Ervin, Jeremy Alan

    In this study, the narratives from a hermeneutical dialectic cycle of three high school students were analyzed to understand the influences of ontological position on the learning of human origins. The interpretation of the narratives provides the reader an opportunity to consider the learning process from the perspective of worldview and conceptual change theories. Questions guiding this research include: Within a context of a worldview, what is the range of ontological positions among a high school AP biology class? To what extent does ontological position influence the learning of scientific concepts about human origins? If a student's ontological position is contradictory to scientific explanation of human origins, how will learning strategies and motivations change? All consenting students in an AP biology class were interviewed in order to select three students who represented three different ontological positions of a worldview: No Supernatural, Supernatural Without Impact, or Supernatural Impact. The issue of worldview is addressed at length in this work. Consenting students had completed the graduation requirements in biology, but were taking an additional biology course in preparation for college. Enrollment in an AP biology course was assumed to indicate that the selected students have an understanding of the concept of human origins at a comprehensive level, but not necessarily at an apprehension level, both being needed for conceptual change. Examination of the narratives reveals that students may alternate between two ontological positions in order to account for inconsistencies within a situation. This relativity enables the range of ontological positions to vary depending on concepts being considered. Not all Supernatural Impact positions conflict with biological understanding of human origins due to the ability of some to create a dichotomy between religion and school. Any comprehended concepts within this dichotomy lead to plagiaristic knowledge rather than conceptual change. When conflicts occur, students employ alternate learning strategies for comprehension, but not apprehension, which result in plagiaristic knowledge. These findings suggest that teachers consider the ontological positions of student worldviews because of the potential influence on knowledge construction and conceptual change, especially about topics involving the theory of evolution.

  3. Histological determination of the human origin of bone fragments.

    PubMed

    Cattaneo, Cristina; Porta, David; Gibelli, Daniele; Gamba, Corrado

    2009-05-01

    A frequently encountered task in the forensic scenario is verification of the human origin of severely degraded fragments of bone. In these cases histological methods which consider osteon size and morphology can prove to be useful. The authors in the present study verify the applicability of published algorithms to flat and subadult bones from human, dog, cat, cow, rabbit, sheep, pig, chicken, quail, and turkey samples. Metric analysis was performed on 2031 Haversian canals. Analyses carried out on human samples confirmed a success rate of around 70% on long adult bones; however the percentage of wrong answers was particularly high in the case of newborns and older subadults as well as on flat bones in general. Results therefore suggest that such regression equations should be limited only to bone fragments from long adult bones. PMID:19298464

  4. Timing the origin of human malarias: the lemur puzzle

    PubMed Central

    2011-01-01

    Background Timing the origin of human malarias has been a focus of great interest. Previous studies on the mitochondrial genome concluded that Plasmodium in primates, including those parasitic to humans, radiated relatively recently during a process where host switches were common. Those investigations, however, assumed constant rate of evolution and tightly bound (fixed) calibration points based on host fossils or host distribution. We investigate the effect of such assumptions using different molecular dating methods. We include parasites from Lemuroidea since their distribution provides an external validation to time estimates allowing us to disregard scenarios that cannot explain their introduction in Madagascar. Results We reject the assumption that the Plasmodium mitochondrial genome, as a unit or each gene separately, evolves at a constant rate. Our analyses show that Lemuroidea parasites are a monophyletic group that shares a common ancestor with all Catarrhini malarias except those related to P. falciparum. However, we found no evidence that this group of parasites branched with their hosts early in the evolution of primates. We applied relaxed clock methods and different calibrations points to explore the origin of primate malarias including those found in African apes. We showed that previous studies likely underestimated the origin of malarial parasites in primates. Conclusions The use of fossils from the host as absolute calibration and the assumption of a strict clock likely underestimate time when performing molecular dating analyses on malarial parasites. Indeed, by exploring different calibration points, we found that the time for the radiation of primate parasites may have taken place in the Eocene, a time consistent with the radiation of African anthropoids. The radiation of the four human parasite lineages was part of such events. The time frame estimated in this investigation, together with our phylogenetic analyses, made plausible a scenario where gorillas and humans acquired malaria from a Pan lineage. PMID:21992100

  5. Virtual assessment of the endocranial morphology of the early modern European fossil calvaria from cioclovina, romania.

    PubMed

    Kranioti, Elena F; Holloway, Ralph; Senck, Sascha; Ciprut, Tudor; Grigorescu, Dan; Harvati, Katerina

    2011-07-01

    Endocasts provide evidence on size and shape characteristics, blood supply trajectories, and neurological features of the brain, allowing comparative analyses of fossil hominins crucial to our understanding of human brain evolution. Here, we assess the morphological features of the virtual endocast of the Cioclovina Upper Paleolithic calvarium, one of the earliest reliably dated European modern human fossils. Our study was conducted on a computed tomography (CT) scan of the original specimen. The endocranial profile was approximated via a semiautomatic segmentation of the CT data. Virtual reconstructions of the endocast were used for assessing the morphological features of the endocranium and for the estimation of the endocranial volume. Cioclovina exhibits a clockwise torque with a small anterior extension of the left frontal lobe over the right one and a protrusion of the right occipital lobe over the left, most likely due to the superior sagittal sinus coursing over the occipital pole. There is an obvious right predominance of the posterior drainage system. Interestingly, the area of the frontal sinus is occupied by dense bony tissue with small air cells corresponding probably to a natural bony loss in the diploë and to vascular spaces. An estimated endocranial volume of 1498.53 cc was calculated. The convolutional details of the third inferior frontal gyrus (Broca's caps) are indistinguishable from those found in modern Homo sapiens, and the left occipital lobe appears wider than the right, a possible correlate of right-handedness. Our metric analysis of endocranial measurements also aligns Cioclovina with modern humans. PMID:21634023

  6. African origin of human-specific polymorphic Alu insertions.

    PubMed Central

    Batzer, M A; Stoneking, M; Alegria-Hartman, M; Bazan, H; Kass, D H; Shaikh, T H; Novick, G E; Ioannou, P A; Scheer, W D; Herrera, R J

    1994-01-01

    Alu elements are a family of interspersed repeats that have mobilized throughout primate genomes by retroposition from a few "master" genes. Among the 500,000 Alu elements in the human genome are members of the human-specific subfamily that are not fixed in the human species; that is, not all chromosomes carry an Alu element at a particular locus. Four such polymorphic human-specific Alu insertions were analyzed by a rapid, PCR-based assay that uses primers that flank the insertion point to determine genotypes based on the presence or absence of the Alu element. These four polymorphic Alu insertions were shown to be absent from the genomes of a number of nonhuman primates, consistent with their arising as human genetic polymorphisms sometime after the human/African ape divergence. Analysis of 664 unrelated individuals from 16 population groups from around the world revealed substantial levels of variation within population groups and significant genetic differentiation among groups. No significant associations were found among the four loci, consistent with their location on different chromosomes. A maximum-likelihood tree of population relationships showed four major groupings consisting of Africa, Europe, Asia/Americas, and Australia/New Guinea, which is concordant with similar trees based on other loci. A particularly useful feature of the polymorphic Alu insertions is that the ancestral state is known to be the absence of the Alu element, and the presence of the Alu element at a particular chromosomal site reflects a single, unique event in human evolution. A hypothetical ancestral group can then be included in the tree analysis, with the frequency of each insertion set to zero. The ancestral group connected to the maximum-likelihood tree within the African branch, which suggests an African origin of these polymorphic Alu insertions. These data are concordant with other diverse data sets, which lends further support to the recent African origin hypothesis for modern humans. Polymorphic Alu insertions represent a source of genetic variation for studying human population structure and evolution. Images PMID:7991620

  7. [Criminal responsibility and confinement of the insane from antiquity to early modern Japan].

    PubMed

    Hiruta, Genshiro

    2003-01-01

    ANTIQUITY: The third Japanese legal code, Youro Ritsuryo, was compiled in 718. The code classified the insane people as severely handicapped, exempted them from taxes and reduced their punishments when they committed a crime. MEDIEVAL: We cannot find any description on criminal responsibility of the insane in the legal documents of this age. EARLY MODERN: In 1742, the Tokugawa government enacted a criminal code named Osadamegaki-hyakkajyo, which contained a clause on the criminal responsibility of the people suffering from insanity or alcoholism. In principle, even if the criminal who committed homicide had been insane, he or she was sentenced to death. However, when the criminal had been obviously insane and the master or relatives of the victim appealed for mercy the judge could spare his/her life. The case of killing under the influence of simple alcohol intoxication was considered to be fully responsible. However, the case of pathological intoxication was treated in the same way as the case of insanity. There was a strict rule for confinement of the insane. When people thought that confinement was inevitable, a petition for confinement was submitted to the court under the joint signature of the family, the members of goningumi (a mutual responsibility unit), and the head of the town or village. In big cities like Edo (now Tokyo), a medical certificate of a doctor was attached to the petition. After receiving the petition, the court dispatched officials to inspect the case. When the court could confirm the necessity of confinement, they gave the permission and sealed the lock of a private cell where the insane was confined. People had to appeal to the court again when they wanted to free the insane from the cell. PMID:12708014

  8. Exploring early modern chemistry: the first twenty-five years of the Society for the Study of Alchemy & Early Modern Chemistry 1935-1960.

    PubMed

    Brock, W H

    2011-11-01

    The article uses the recently deposited archives of the Society for the History of Alchemy and Chemistry to explore the ideas, motives and disagreements of its founders and officers between 1935 and 1960. The origin of the title Ambix for the society's journal is also explained. An appendix identifies the initial membership of the society. PMID:22397154

  9. ISSag1 in streptococcal strains of human and animal origin.

    PubMed

    Franken, Carmen; Brandt, Claudia; Brker, Gerd; Spellerberg, Barbara

    2004-10-01

    The chromosomal region of Streptococcus agalactiae harboring the C5a peptidase and the lmb genes displays the structure of a composite transposon. Its presence in a streptococcal strain is associated with the origin of this strain from a human host. In S. agalactiae it is flanked by two copies of the insertion element ISSag2, and the nucleotide sequence for a third IS element (ISSag1) can be found in this region. Based on amino acid sequence similarity of the deduced transposase ISSag1 belongs to the IS3 family. It is 1251 bp long and flanked by 37 bp imperfect inverted repeats. Horizontal gene transfer among different bacterial species is facilitated by mobile genetic elements. To investigate if ISSag1 homologues are also present in other streptococcal species, various species of pyogenic streptococci from animal and human origin were analyzed by Southern blot hybridization and PCR. Among the different streptococcal species, multiple copies of an ISSag1 homologue could only be detected in S. dysgalactiae subsp. dysgalactiae strains of animal origin. All of the S. agalactiae strains harbored only a single copy, that was always found in strains with the scpB-lmb composite transposon. A single copy of an ISSag1 homologue could also be detected in some of the S. pyogenes and S. dysgalactiae subsp. equisimilis strains. Nucleotide sequencing of the IS element in S. dysgalactiae subsp. dysgalactiae strains revealed several different variants. One of the variants showed the features of a regular IS3 element. The other two variants that were observed displayed a 500-bp deletion and a mosaic structure composed of ISSag1 and ISSag2 homologues. This mosaic structure suggests that recombination and horizontal gene transfer events in S. dysgalactiae strains of bovine origin could have played a role in the assembly of the scpB-lmb composite transposon structure. PMID:15532982

  10. Phenotypic differentiation of bifidobacteria of human and animal origins.

    PubMed

    Gavini, F; Pourcher, A M; Neut, C; Monget, D; Romond, C; Oger, C; Izard, D

    1991-10-01

    The phenotypes of 153 strains belonging or related to the genus Bifidobacterium were studied. These organisms included 38 collection strains and 115 wild strains (41 strains of human origin, 56 strains of animal origin, and 18 strains obtained from rivers or sewage). Our phenotypic analysis revealed seven main groups that were subdivided into 20 subgroups. Seven subgroups contained no type or collection strain. Among the human strains, the type strains of Bifidobacterium pseudocatenulatum and B. catenulatum fell into group I, which contained the type strains of B. adolescentis (subgroup Ib), B. dentium (subgroup Ic), and B. angulatum (ungrouped). The type strain of B. breve belonged to subgroup IIIa1, and the type strains of B. infantis and B. longum fell into subgroup IIIb1. Group VII comprised only wild strains that were isolated from human infant feces. Among the animal strains, group II consisted mainly of bifidobacteria that were isolated from pig feces and contained the type strains of B. suis (subgroup IIb), B. thermophilum (subgroup IIf), B. choerinum, and B. boum (ungrouped). Wild strains belonging to group V were isolated from pig, calf, cow, and chicken feces; this included the type strains of B. animalis (subgroup Va), B. magnum (subgroup Vb), B. pseudolongum, and B. globosum (subgroup Vc). The strains of human origin (groups I, III, and VII) were well separated from the animal strains (groups II, IV, and V). It was not surprising that the wild strains isolated from surface water or sewage were distributed in the animal groups as well as the human groups. Thus, bifidobacteria can be considered to be successful indicators of human or animal fecal pollution when they are correctly classified. The acidification patterns were not adequate to differentiate Bifidobacterium species, as determined previously by Mitsuoka (Bifidobacteria Microflora 3:11-28, 1984) and Scardovi (p. 1418-1434, in P. H. A. Sneath, N. S. Mair, M. E. Sharpe, and J. G. Holt, ed., Bergey's Manual of Systematic Bacteriology, vol. 2, 1986). However, enzymatic tests furnished new taxonomic criteria for the genus. PMID:1742200

  11. The motor origins of human and avian song structure

    PubMed Central

    Tierney, Adam T.; Russo, Frank A.; Patel, Aniruddh D.

    2011-01-01

    Human song exhibits great structural diversity, yet certain aspects of melodic shape (how pitch is patterned over time) are widespread. These include a predominance of arch-shaped and descending melodic contours in musical phrases, a tendency for phrase-final notes to be relatively long, and a bias toward small pitch movements between adjacent notes in a melody [Huron D (2006) Sweet Anticipation: Music and the Psychology of Expectation (MIT Press, Cambridge, MA)]. What is the origin of these features? We hypothesize that they stem from motor constraints on song production (i.e., the energetic efficiency of their underlying motor actions) rather than being innately specified. One prediction of this hypothesis is that any animals subject to similar motor constraints on song will exhibit similar melodic shapes, no matter how distantly related those animals are to humans. Conversely, animals who do not share similar motor constraints on song will not exhibit convergent melodic shapes. Birds provide an ideal case for testing these predictions, because their peripheral mechanisms of song production have both notable similarities and differences from human vocal mechanisms [Riede T, Goller F (2010) Brain Lang 115:69–80]. We use these similarities and differences to make specific predictions about shared and distinct features of human and avian song structure and find that these predictions are confirmed by empirical analysis of diverse human and avian song samples. PMID:21876156

  12. Middle cranial fossa anatomy and the origin of modern humans.

    PubMed

    Bastir, Markus; Rosas, Antonio; Lieberman, Daniel E; O'Higgins, Paul

    2008-02-01

    Anatomically, modern humans differ from archaic forms in possessing a globular neurocranium and a retracted face and in cognitive functions, many of which are associated with the temporal lobes. The middle cranial fossa (MCF) interacts during growth and development with the temporal lobes, the midface, and the mandible. It has been proposed that evolutionary transformations of the MCF (perhaps from modification of the temporal lobes) can have substantial influences on craniofacial morphology. Here, we use three-dimensional (3D) geometric morphometrics and computer reconstructions of computed tomography-scanned fossil hominids, fossil and recent modern humans and chimpanzees to address this issue further. Mean comparisons and permutation analyses of scaled 3D basicranial landmarks confirm that the MCF of Homo sapiens is highly significantly different (P < 0.001) from H. neanderthalensis, H. heidelbergensis, and Pan troglodytes. Modern humans have a unique configuration with relatively more anterolateral projection of the MCF pole relative to the optic chiasm and the foramen rotundum. These findings are discussed in the context of evolutionary changes in craniofacial morphology and the origins of modern human autapomorphies. In particular, the findings of this study point to variations in the temporal lobe, which, through effects on the MCF and face, are central to the evolution of modern human facial form. PMID:18213701

  13. Immunohistochemical analyses point to epidermal origin of human Merkel cells.

    PubMed

    Tilling, Thomas; Wladykowski, Ewa; Failla, Antonio Virgilio; Houdek, Pia; Brandner, Johanna M; Moll, Ingrid

    2014-04-01

    Merkel cells, the neurosecretory cells of skin, are essential for light-touch responses and may probably fulfill additional functions. Whether these cells derive from an epidermal or a neural lineage has been a matter of dispute for a long time. In mice, recent studies have clearly demonstrated an epidermal origin of Merkel cells. Given the differences in Merkel cell distribution between human and murine skin, it is, however, unclear whether the same holds true for human Merkel cells. We therefore attempted to gain insight into the human Merkel cell lineage by co-immunodetection of the Merkel cell marker protein cytokeratin 20 (CK20) with various proteins known to be expressed either in epidermal or in neural stem cells of the skin. Neither Sox10 nor Pax3, both established markers of the neural crest lineage, exhibited any cell co-labeling with CK20. By contrast, β1 integrin, known to be enriched in epidermal stem cells, was found in nearly 70 % of interfollicular epidermal and 25 % of follicular Merkel cells. Moreover, LRIG1, also enriched in epidermal stem cells, displayed significant co-immunolabeling with CK20 as well (approximately 20 % in the interfollicular epidermis and 7 % in the hair follicle, respectively). Further epidermal markers were detected in sporadic Merkel cells. Cells co-expressing CK20 with epidermal markers may represent a transitory state between stem cells and differentiated cells. β1 integrin is probably also synthesized by a large subset of mature Merkel cells. Summarizing, our data suggest that human Merkel cells may originate from epidermal rather than neural progenitors. PMID:24292845

  14. Human origins and evolution: Cold Spring Harbor, deja vu.

    PubMed

    White, T D

    2009-01-01

    The Cold Spring Harbor Symposia of the 1950s were key to integrating human evolutionary studies into biology. That integration provided a solid foundation for systematic and functional interpretations of an expanding base of fossil and molecular evidence during the latter half of the 20th century. Today, the paleontological record of human evolution amassed during the last 150 years illuminates the human clade on life's tree. However, the rise of Hennegian parsimony cladistics and punctuationalism during the end of the last century witnessed the partial abandonment of classificatory conventions cemented by Mayr, Simpson, Dobzhansky, and others at Cold Spring Harbor. This has led to an artificial, postmillennial amplification of apparent species diversity in the hominid clade. Work on a stratigraphically thick and temporally deep sedimentary sequence in the Middle Awash study area of Ethiopia's Afar Depression reveals an assembly order of hominid anatomies and behaviors that was impossible for Darwin to discern. Large parts of that record appear to reflect phyletic evolution, consistent with the lessons and expectations of Cold Spring Harbor in 1950. Molecular biology cannot reveal the assembly sequences or contexts of human origins and evolution without reference to adequate geological, geochronological, paleobiological, and archaeological records. Today's consilience of these disparate data sets would have impressed Charles Darwin. PMID:19776166

  15. Evolutionary Origins of Human Herpes Simplex Viruses 1 and 2

    PubMed Central

    Wertheim, Joel O.; Smith, Martin D.; Smith, Davey M.; Scheffler, Konrad; Kosakovsky Pond, Sergei L.

    2014-01-01

    Herpesviruses have been infecting and codiverging with their vertebrate hosts for hundreds of millions of years. The primate simplex viruses exemplify this pattern of virus–host codivergence, at a minimum, as far back as the most recent common ancestor of New World monkeys, Old World monkeys, and apes. Humans are the only primate species known to be infected with two distinct herpes simplex viruses: HSV-1 and HSV-2. Human herpes simplex viruses are ubiquitous, with over two-thirds of the human population infected by at least one virus. Here, we investigated whether the additional human simplex virus is the result of ancient viral lineage duplication or cross-species transmission. We found that standard phylogenetic models of nucleotide substitution are inadequate for distinguishing among these competing hypotheses; the extent of synonymous substitutions causes a substantial underestimation of the lengths of some of the branches in the phylogeny, consistent with observations in other viruses (e.g., avian influenza, Ebola, and coronaviruses). To more accurately estimate ancient viral divergence times, we applied a branch-site random effects likelihood model of molecular evolution that allows the strength of natural selection to vary across both the viral phylogeny and the gene alignment. This selection-informed model favored a scenario in which HSV-1 is the result of ancient codivergence and HSV-2 arose from a cross-species transmission event from the ancestor of modern chimpanzees to an extinct Homo precursor of modern humans, around 1.6 Ma. These results provide a new framework for understanding human herpes simplex virus evolution and demonstrate the importance of using selection-informed models of sequence evolution when investigating viral origin hypotheses. PMID:24916030

  16. Evolutionary origins of human herpes simplex viruses 1 and 2.

    PubMed

    Wertheim, Joel O; Smith, Martin D; Smith, Davey M; Scheffler, Konrad; Kosakovsky Pond, Sergei L

    2014-09-01

    Herpesviruses have been infecting and codiverging with their vertebrate hosts for hundreds of millions of years. The primate simplex viruses exemplify this pattern of virus-host codivergence, at a minimum, as far back as the most recent common ancestor of New World monkeys, Old World monkeys, and apes. Humans are the only primate species known to be infected with two distinct herpes simplex viruses: HSV-1 and HSV-2. Human herpes simplex viruses are ubiquitous, with over two-thirds of the human population infected by at least one virus. Here, we investigated whether the additional human simplex virus is the result of ancient viral lineage duplication or cross-species transmission. We found that standard phylogenetic models of nucleotide substitution are inadequate for distinguishing among these competing hypotheses; the extent of synonymous substitutions causes a substantial underestimation of the lengths of some of the branches in the phylogeny, consistent with observations in other viruses (e.g., avian influenza, Ebola, and coronaviruses). To more accurately estimate ancient viral divergence times, we applied a branch-site random effects likelihood model of molecular evolution that allows the strength of natural selection to vary across both the viral phylogeny and the gene alignment. This selection-informed model favored a scenario in which HSV-1 is the result of ancient codivergence and HSV-2 arose from a cross-species transmission event from the ancestor of modern chimpanzees to an extinct Homo precursor of modern humans, around 1.6 Ma. These results provide a new framework for understanding human herpes simplex virus evolution and demonstrate the importance of using selection-informed models of sequence evolution when investigating viral origin hypotheses. PMID:24916030

  17. Body proportions in Late Pleistocene Europe and modern human origins.

    PubMed

    Holliday, T W

    1997-05-01

    Body proportions covary with climate, apparently as the result of climatic selection. Ontogenic research and migrant studies have demonstrated that body proportions are largely genetically controlled and are under low selective rates; thus studies of body form can provide evidence for evolutionarily short-term dispersals and/or gene flow. Following these observations, competing models of modern human origins yield different predictions concerning body proportion shifts in Late Pleistocene Europe. Replacement predicts that the earliest modern Europeans will possess "tropical" body proportions (assuming Africa is the center of origin), while Regional Continuity permits only minor shifts in body shape, due to climatic change and/or improved cultural buffering. This study tests these predictions via analyses of osteometric data reflective of trunk height and breadth, limb proportions and relative body mass for samples of Early Upper Paleolithic (EUP), Late Upper Paleolithic (LUP) and Mesolithic (MES) humans and 13 recent African and European populations. Results reveal a clear tendency for the EUP sample to cluster with recent Africans, while LUP and MES samples cluster with recent Europeans. These results refute the hypothesis of local continuity in Europe, and are consistent with an interpretation of elevated gene flow (and population dispersal?) from Africa, followed by subsequent climatic adaptation to colder conditions. These data do not, however, preclude the possibility of some (albeit small) contribution of genes from Neandertals to succeeding populations, as is postulated in Bräuer's "Afro-European Sapiens" model. PMID:9169992

  18. The origin of human multi-modal communication

    PubMed Central

    Levinson, Stephen C.; Holler, Judith

    2014-01-01

    One reason for the apparent gulf between animal and human communication systems is that the focus has been on the presence or the absence of language as a complex expressive system built on speech. But language normally occurs embedded within an interactional exchange of multi-modal signals. If this larger perspective takes central focus, then it becomes apparent that human communication has a layered structure, where the layers may be plausibly assigned different phylogenetic and evolutionary origins—especially in the light of recent thoughts on the emergence of voluntary breathing and spoken language. This perspective helps us to appreciate the different roles that the different modalities play in human communication, as well as how they function as one integrated system despite their different roles and origins. It also offers possibilities for reconciling the ‘gesture-first hypothesis’ with that of gesture and speech having evolved together, hand in hand—or hand in mouth, rather—as one system. PMID:25092670

  19. Reexamining human origins in light of Ardipithecus ramidus.

    PubMed

    Lovejoy, C Owen

    2009-10-01

    Referential models based on extant African apes have dominated reconstructions of early human evolution since Darwin's time. These models visualize fundamental human behaviors as intensifications of behaviors observed in living chimpanzees and/or gorillas (for instance, upright feeding, male dominance displays, tool use, culture, hunting, and warfare). Ardipithecus essentially falsifies such models, because extant apes are highly derived relative to our last common ancestors. Moreover, uniquely derived hominid characters, especially those of locomotion and canine reduction, appear to have emerged shortly after the hominid/chimpanzee divergence. Hence, Ardipithecus provides a new window through which to view our clade's earliest evolution and its ecological context. Early hominids and extant apes are remarkably divergent in many cardinal characters. We can no longer rely on homologies with African apes for accounts of our origins and must turn instead to general evolutionary theory. A proposed adaptive suite for the emergence of Ardipithecus from the last common ancestor that we shared with chimpanzees accounts for these principal ape/human differences, as well as the marked demographic success and cognitive efflorescence of later Plio-Pleistocene hominids. PMID:19810200

  20. The digital origin of human language--a synthesis.

    PubMed

    Noll, Hans

    2003-05-01

    The fact that all languages known are digital poses the question of their origin. The answer developed here treats language as the interface of information theory and molecular development by showing previously unrecognized isomorphisms between the analog and digital features of language and life at the molecular level. Human language is a special case of signal transduction and hence is subject to the coding aspects of Shannon's theorems and the analog aspects of pattern recognition, each represented by genotype and phenotype. Digital language acquisition is late in evolution and postnatal development and requires a neural reorganization by a mechanism of somatic network programming in response to the environment. Such a mechanism would solve the Chomsky conundrum of how children can learn any language without knowing rules of grammar too numerous to be encoded genotypically. PMID:12717819

  1. Influenza A Viruses of Human Origin in Swine, Brazil.

    PubMed

    Nelson, Martha I; Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis

    2015-08-01

    The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil's swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009-2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance. PMID:26196759

  2. Influenza A Viruses of Human Origin in Swine, Brazil

    PubMed Central

    Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis

    2015-01-01

    The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil’s swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009–2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance. PMID:26196759

  3. Human origin of Bacteroides fragilis bacteriophages present in the environment.

    PubMed Central

    Tartera, C; Lucena, F; Jofre, J

    1989-01-01

    Bacteroides fragilis HSP40 phages have been detected in waters with various levels of fecal contamination of human origin. The average numbers of B. fragilis phages present in sewage water reached 5.3 x 10(3) per 100 ml of water. We found a number 1,000 times lower in a river contaminated with domestic sewage only, in which the levels of fecal coliforms and fecal streptococci were 10,000 times lower than those found in raw sewage. In addition, B. fragilis phages were not found in significant numbers in slaughterhouse wastewaters. They were not present in fecal-polluted waters containing fecal contamination from wildlife only. Although the number of B. fragilis phages present in contaminated waters was lower than the number of coliphages, their presence indicated human fecal contamination. It is also shown that Bacteroides phages are only able to multiply under anaerobic conditions in the presence of nutrients, and they cannot multiply in natural waters and sediments. PMID:2604407

  4. Origins of De Novo Genes in Human and Chimpanzee.

    PubMed

    Ruiz-Orera, Jorge; Hernandez-Rodriguez, Jessica; Chiva, Cristina; Sabidó, Eduard; Kondova, Ivanela; Bontrop, Ronald; Marqués-Bonet, Tomàs; Albà, M Mar

    2015-12-01

    The birth of new genes is an important motor of evolutionary innovation. Whereas many new genes arise by gene duplication, others originate at genomic regions that did not contain any genes or gene copies. Some of these newly expressed genes may acquire coding or non-coding functions and be preserved by natural selection. However, it is yet unclear which is the prevalence and underlying mechanisms of de novo gene emergence. In order to obtain a comprehensive view of this process, we have performed in-depth sequencing of the transcriptomes of four mammalian species--human, chimpanzee, macaque, and mouse--and subsequently compared the assembled transcripts and the corresponding syntenic genomic regions. This has resulted in the identification of over five thousand new multiexonic transcriptional events in human and/or chimpanzee that are not observed in the rest of species. Using comparative genomics, we show that the expression of these transcripts is associated with the gain of regulatory motifs upstream of the transcription start site (TSS) and of U1 snRNP sites downstream of the TSS. In general, these transcripts show little evidence of purifying selection, suggesting that many of them are not functional. However, we find signatures of selection in a subset of de novo genes which have evidence of protein translation. Taken together, the data support a model in which frequently-occurring new transcriptional events in the genome provide the raw material for the evolution of new proteins. PMID:26720152

  5. Can chimpanzee biology highlight human origin and evolution?

    PubMed

    Roffman, Itai; Nevo, Eviatar

    2010-07-01

    The closest living relatives of humans are their chimpanzee/bonobo (Pan) sister species, members of the same subfamily "Homininae". This classification is supported by over 50 years of research in the fields of chimpanzee cultural diversity, language competency, genomics, anatomy, high cognition, psychology, society, self-consciousness and relation to others, tool use/production, as well as Homo level emotions, symbolic competency, memory recollection, complex multifaceted problem-solving capabilities, and interspecies communication. Language competence and symbolism can be continuously bridged from chimpanzee to man. Emotions, intercommunity aggression, body language, gestures, facial expressions, and vocalization of intonations seem to parallel between the sister taxa Homo and Pan. The shared suite of traits between Pan and Homo genus demonstrated in this article integrates old and new information on human-chimpanzee evolution, bilateral informational and cross-cultural exchange, promoting the urgent need for Pan cultures in the wild to be protected, as they are part of the cultural heritage of mankind. Also, we suggest that bonobos, Pan paniscus, based on shared traits with Australopithecus, need to be included in Australopithecine's subgenus, and may even represent living-fossil Australopithecines. Unfolding bonobo and chimpanzee biology highlights our common genetic and cultural evolutionary origins. PMID:23908781

  6. Origins of De Novo Genes in Human and Chimpanzee

    PubMed Central

    Ruiz-Orera, Jorge; Hernandez-Rodriguez, Jessica; Chiva, Cristina; Sabidó, Eduard; Kondova, Ivanela; Bontrop, Ronald; Marqués-Bonet, Tomàs; Albà, M.Mar

    2015-01-01

    The birth of new genes is an important motor of evolutionary innovation. Whereas many new genes arise by gene duplication, others originate at genomic regions that did not contain any genes or gene copies. Some of these newly expressed genes may acquire coding or non-coding functions and be preserved by natural selection. However, it is yet unclear which is the prevalence and underlying mechanisms of de novo gene emergence. In order to obtain a comprehensive view of this process, we have performed in-depth sequencing of the transcriptomes of four mammalian species—human, chimpanzee, macaque, and mouse—and subsequently compared the assembled transcripts and the corresponding syntenic genomic regions. This has resulted in the identification of over five thousand new multiexonic transcriptional events in human and/or chimpanzee that are not observed in the rest of species. Using comparative genomics, we show that the expression of these transcripts is associated with the gain of regulatory motifs upstream of the transcription start site (TSS) and of U1 snRNP sites downstream of the TSS. In general, these transcripts show little evidence of purifying selection, suggesting that many of them are not functional. However, we find signatures of selection in a subset of de novo genes which have evidence of protein translation. Taken together, the data support a model in which frequently-occurring new transcriptional events in the genome provide the raw material for the evolution of new proteins. PMID:26720152

  7. Short Faces, Big Tongues: Developmental Origin of the Human Chin

    PubMed Central

    Coquerelle, Michael; Prados-Frutos, Juan Carlos; Rojo, Rosa; Mitteroecker, Philipp; Bastir, Markus

    2013-01-01

    During the course of human evolution, the retraction of the face underneath the braincase, and closer to the cervical column, has reduced the horizontal dimension of the vocal tract. By contrast, the relative size of the tongue has not been reduced, implying a rearrangement of the space at the back of the vocal tract to allow breathing and swallowing. This may have left a morphological signature such as a chin (mental prominence) that can potentially be interpreted in Homo. Long considered an autopomorphic trait of Homo sapiens, various extinct hominins show different forms of mental prominence. These features may be the evolutionary by-product of equivalent developmental constraints correlated with an enlarged tongue. In order to investigate developmental mechanisms related to this hypothesis, we compare modern 34 human infants against 8 chimpanzee fetuses, whom development of the mandibular symphysis passes through similar stages. The study sets out to test that the shared ontogenetic shape changes of the symphysis observed in both species are driven by the same factor – the space restriction at the back of the vocal tract and the associated arrangement of the tongue and hyoid bone. We apply geometric morphometric methods to extensive three-dimensional anatomical landmarks and semilandmarks configuration, capturing the geometry of the cervico-craniofacial complex including the hyoid bone, tongue muscle and the mandible. We demonstrate that in both species, the forward displacement of the mental region derives from the arrangement of the tongue and hyoid bone, in order to cope with the relative horizontal narrowing of the oral cavity. Because humans and chimpanzees share this pattern of developmental integration, the different forms of mental prominence seen in some extinct hominids likely originate from equivalent ontogenetic constraints. Variations in this process could account for similar morphologies. PMID:24260566

  8. Original antigenic sin with human bocaviruses 1-4.

    PubMed

    Li, Xuemeng; Kantola, Kalle; Hedman, Lea; Arku, Benedict; Hedman, Klaus; Sderlund-Venermo, Maria

    2015-10-01

    Human bocavirus (HBoV) 1 is a widespread parvovirus causing acute respiratory disease in young children. In contrast, HBoV2 occurs in the gastrointestinal tract and is potentially associated with gastroenteritis, whilst HBoV3 and -4 infections are less frequent and have not yet been linked with human disease. Due to HBoV1 DNA persistence in the nasopharynx, serology has been advocated as a better alternative for diagnosing acute infections. In constitutionally healthy children, we previously noted that pre-existing HBoV2 immunity in a subsequent HBoV1 infection typically resulted in low or non-existent HBoV1-specific antibody responses. A phenomenon describing such immunological events among related viruses has been known since the 1950s as 'original antigenic sin' (OAS). The aim of this study was to characterize this putative OAS phenomenon in a more controlled setting. Follow-up sera of 10 rabbit pairs, inoculated twice with HBoV1-4 virus-like particles (VLPs) or control antigens, in various combinations, were analysed with HBoV1-4 IgG enzyme immunoassays with and without depletion of heterotypic HBoV antibodies. There were no significant IgG boosts after the second inoculation in either the heterologously or the homologously HBoV-inoculated rabbits, but a clear increase in cross-reactivity was seen with time. We could, however, distinguish a distinct OAS pattern from plain cross-reactivity: half of the heterologously inoculated rabbits showed IgG patterns representative of the OAS hypothesis, in line with our prior results with naturally infected children. HBoVs are the first parvoviruses to show the possible existence of OAS. Our findings provide new information on HBoV1-4 immunity and emphasize the complexity of human bocavirus diagnosis. PMID:26224569

  9. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

    PubMed Central

    Fukusumi, Hayato; Shofuda, Tomoko; Bamba, Yohei; Yamamoto, Atsuyo; Kanematsu, Daisuke; Handa, Yukako; Okita, Keisuke; Nakamura, Masaya; Yamanaka, Shinya; Okano, Hideyuki; Kanemura, Yonehiro

    2016-01-01

    Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes. PMID:27212953

  10. ‘To[o] much eating stifles the child’: fat bodies and reproduction in early modern England†

    PubMed Central

    Toulalan, Sarah

    2013-01-01

    Abstract This article examines associations between fat bodies and reproductive dysfunction that were prevalent in medical, midwifery and other literature in early modern England. In a period when fertility and successful reproduction were regarded as hugely important for social, economic and political stability such associations further contributed to negative attitudes towards fat bodies that were fuelled by connection with the vices of sloth and gluttony. Fat bodies were categorized as inherently, constitutionally, less sexual and reproductively successful. Consequently they were perceived as unhealthy and unfit for their primary purpose once they had reached sexual maturity: marriage and the production of children. PMID:25960608

  11. Tracing sexual identities in "old age": gender and seniority in advice literature of the early-modern and modern periods.

    PubMed

    van Tilburg, Marja

    2009-10-01

    Thus far, historians have interpreted representations of elderly women with reference to women's roles or to women's positions in society. This article proposes a different approach toward gender: to relate representations of the aged to the sexual identities of both men and women. This article analyzes representations of old age in conduct books of the early-modern period and the nineteenth century. By drawing a comparison, the eighteenth-century change of "identity regime" in European culture is brought to the fore. The article points to the influence of sexual identities on the representations of senior persons in advice literature both in Dutch and translated into Dutch. PMID:19999638

  12. Testing modern human out-of-Africa dispersal models and implications for modern human origins.

    PubMed

    Reyes-Centeno, Hugo; Hubbe, Mark; Hanihara, Tsunehiko; Stringer, Chris; Harvati, Katerina

    2015-10-01

    The modern human expansion process out of Africa has important implications for understanding the genetic and phenotypic structure of extant populations. While intensely debated, the primary hypotheses focus on either a single dispersal or multiple dispersals out of the continent. Here, we use the human fossil record from Africa and the Levant, as well as an exceptionally large dataset of Holocene human crania sampled from Asia, to model ancestor-descendant relationships along hypothetical dispersal routes. We test the spatial and temporal predictions of competing out-of-Africa models by assessing the correlation of geographical distances between populations and measures of population differentiation derived from quantitative cranial phenotype data. Our results support a model in which extant Australo-Melanesians are descendants of an initial dispersal out of Africa by early anatomically modern humans, while all other populations are descendants of a later migration wave. Our results have implications for understanding the complexity of modern human origins and diversity. PMID:26164107

  13. Analysis of the origin of predictability in human communications

    NASA Astrophysics Data System (ADS)

    Zhang, Lin; Liu, Yani; Wu, Ye; Xiao, Jinghua

    2014-01-01

    Human behaviors in daily life can be traced by their communications via electronic devices. E-mails, short messages and cell-phone calls can be used to investigate the predictability of communication partners’ patterns, because these three are the most representative and common behaviors in daily communications. In this paper, we show that all the three manners have apparent predictability in partners’ patterns, and moreover, the short message users’ sequences have the highest predictability among the three. We also reveal that people with fewer communication partners have higher predictability. Finally, we investigate the origin of predictability, which comes from two aspects: one is the intrinsic pattern in the partners sequence, that is, people have the preference of communicating with a fixed partner after another fixed one. The other aspect is the burst, which is communicating with the same partner several times in a row. The high burst in short message communication pattern is one of the main reasons for its high predictability, the intrinsic pattern in e-mail partners sequence is the main reason for its predictability, and the predictability of cell-phone call partners sequence comes from both aspects.

  14. Can Chimpanzee Biology Highlight Human Origin and Evolution?

    PubMed Central

    Roffman, Itai; Nevo, Eviatar

    2010-01-01

    The closest living relatives of humans are their chimpanzee/bonobo (Pan) sister species, members of the same subfamily “Homininae”. This classification is supported by over 50 years of research in the fields of chimpanzee cultural diversity, language competency, genomics, anatomy, high cognition, psychology, society, self-consciousness and relation to others, tool use/production, as well as Homo level emotions, symbolic competency, memory recollection, complex multifaceted problem-solving capabilities, and interspecies communication. Language competence and symbolism can be continuously bridged from chimpanzee to man. Emotions, intercommunity aggression, body language, gestures, facial expressions, and vocalization of intonations seem to parallel between the sister taxa Homo and Pan. The shared suite of traits between Pan and Homo genus demonstrated in this article integrates old and new information on human–chimpanzee evolution, bilateral informational and cross-cultural exchange, promoting the urgent need for Pan cultures in the wild to be protected, as they are part of the cultural heritage of mankind. Also, we suggest that bonobos, Pan paniscus, based on shared traits with Australopithecus, need to be included in Australopithecine’s subgenus, and may even represent living-fossil Australopithecines. Unfolding bonobo and chimpanzee biology highlights our common genetic and cultural evolutionary origins. PMID:23908781

  15. Children’s Physic: Medical Perceptions and Treatment of Sick Children in Early Modern England, c. 1580–1720

    PubMed Central

    Newton, Hannah

    2015-01-01

    Summary Historians of medicine, childhood and paediatrics have often assumed that early modern doctors neither treated children, nor adapted their medicines to suit the peculiar temperaments of the young. Through an examination of medical textbooks and doctors’ casebooks, this article refutes these assumptions. It argues that medical authors and practising doctors regularly treated children, and were careful to tailor their remedies to complement the distinctive constitutions of children. Thus, this article proposes that a concept of ‘children’s physic’ existed in early modern England. This term refers to the notion that children were physiologically distinct, requiring special medical care. Children’s physic was rooted in the ancient traditions of Hippocratic and Galenic medicine: it was the child’s humoral make-up that underpinned all medical ideas about children’s bodies, minds, diseases and treatments. Children abounded in the humour blood, which made them humid and weak, and in need of medicines of a particularly gentle nature. PMID:26306061

  16. Historical DNA reveals the demographic history of Atlantic cod (Gadus morhua) in medieval and early modern Iceland

    PubMed Central

    Ólafsdóttir, Guðbjörg Ásta; Westfall, Kristen M.; Edvardsson, Ragnar; Pálsson, Snæbjörn

    2014-01-01

    Atlantic cod (Gadus morhua) vertebrae from archaeological sites were used to study the history of the Icelandic Atlantic cod population in the time period of 1500–1990. Specifically, we used coalescence modelling to estimate population size and fluctuations from the sequence diversity at the cytochrome b (cytb) and Pantophysin I (PanI) loci. The models are consistent with an expanding population during the warm medieval period, large historical effective population size (NE), a marked bottleneck event at 1400–1500 and a decrease in NE in early modern times. The model results are corroborated by the reduction of haplotype and nucleotide variation over time and pairwise population distance as a significant portion of nucleotide variation partitioned across the 1550 time mark. The mean age of the historical fished stock is high in medieval times with a truncation in age in early modern times. The population size crash coincides with a period of known cooling in the North Atlantic, and we conclude that the collapse may be related to climate or climate-induced ecosystem change. PMID:24403343

  17. AFRICAN GENETIC DIVERSITY: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

    PubMed Central

    Campbell, Michael C.; Tishkoff, Sarah A.

    2010-01-01

    Comparative studies of ethnically diverse human populations, particularly in Africa, are important for reconstructing human evolutionary history and for understanding the genetic basis of phenotypic adaptation and complex disease. African populations are characterized by greater levels of genetic diversity, extensive population substructure, and less linkage disequilibrium (LD) among loci compared to non-African populations. Africans also possess a number of genetic adaptations that have evolved in response to diverse climates and diets, as well as exposure to infectious disease. This review summarizes patterns and the evolutionary origins of genetic diversity present in African populations, as well as their implications for the mapping of complex traits, including disease susceptibility. PMID:18593304

  18. ‘A Wonderfull Monster Borne in Germany’: Hairy Girls in Medieval and Early Modern German Book, Court and Performance Culture*

    PubMed Central

    Katritzky, MA

    2014-01-01

    Human hirsuteness, or pathological hair growth, can be symptomatic of various conditions, including genetic mutation or inheritance, and some cancers and hormonal disturbances. Modern investigations into hirsuteness were initiated by nineteenth-century German physicians. Most early modern European cases of hypertrichosis (genetically determined all-over body and facial hair) involve German-speaking parentage or patronage, and are documented in German print culture. Through the Wild Man tradition, modern historians routinely link early modern reception of historical hypertrichosis cases to issues of ethnicity without, however, recognising early modern awareness of links between temporary hirsuteness and the pathological nexus of starvation and anorexia. Here, four cases of hirsute females are reconsidered with reference to this medical perspective, and to texts and images uncovered by my current research at the Herzog August Library and German archives. One concerns an Italian girl taken to Prague in 1355 by the Holy Roman Empress, Anna von Schweidnitz. Another focuses on Madeleine and Antonietta Gonzalez, daughters of the ‘Wild Man’ of Tenerife, documented at German courts in the 1580s. The third and fourth cases consider the medieval bearded Sankt Kümmernis (also known as St Wilgefortis or St Uncumber), and the seventeenth-century Bavarian fairground performer Barbara Urslerin. Krankhafter menschlicher Hirsutismus kann aufgrund unterschiedlicher Ursachen auftreten, zu denen u.a. genetische Veränderungen und Vererbung, verschiedene Krebserkrankungen und hormonelle Störungen gehören. Die moderne Hirsutismus-Forschung ist im 19. Jh. von deutschen Forschern initiiert worden. Die meisten europäischen frühneuzeitlichen Erscheinungen von Hypertrichose (dem genetisch bedingten Haarwuchs am gesamten Körper und im Gesicht) gehen auf deutschsprachige Eltern oder Förderer zurück und sind in Deutschland in den Druck gelangt. Bei Untersuchungen des Motivs des Wilden Mannes zieht die aktuelle geschichtswissenschaftliche Forschung in der Regel Verbindungslinien zwischen der frühneuzeitlichen Wahrnehmung von Hypertrichose-Fällen und Fragen der Ethnizität, ohne jedoch zu beachten, dass in der Frühen Neuzeit die Verbindung zwischen temporärem Hirsutismus und der krankhaften Verknüpfung von Unterernährung und Anorexie bekannt war. Im vorliegenden Beitrag werden vier Fälle von an Hirsutismus erkrankten Frauen neu analysiert, unter Einbezug dieser medizinischen Perspektive und unter Beachtung von Texten und Abbildungen, die meine jüngsten Forschungen in der Herzog August Bibliothek und an deutschen Archiven ans Licht gefördert haben. Die hier betrachteten Fälle betreffen ein italienisches Mädchen, das 1355 von Anna von Schweidnitz, Kaiserin des Hl. Römischen Reichs, nach Prag gebracht wurde; Madeleine und Antonietta Gonzalez, die Töchter des ‘Wilden Manns’ von Teneriffa, die in den 1580er Jahren an deutschen Höfen bezeugt sind; die bärtige Sankt Kümmernis (Wilgefortis), und die bayerische Jahrmarktkünstlerin Barbara Urslerin. PMID:25598545

  19. Romanticism, the Avant-Garde, and the Early Modern Innovators in Arts Education.

    ERIC Educational Resources Information Center

    Leeds, Jo Alice

    1985-01-01

    The contributions of major avant-garde innovators, e.g., Cizek, Jaques-Dalcroze, Laban, Lowenfeld, Orff, Kodaly, and Mearns, who worked to establish the creative process as an important means of human education are discussed. (RM)

  20. Origins.

    ERIC Educational Resources Information Center

    Online-Offline, 1999

    1999-01-01

    Provides an annotated list of resources dealing with the theme of origins of life, the universe, and traditions. Includes Web sites, videos, books, audio materials, and magazines with appropriate grade levels and/or subject disciplines indicated; professional resources; and learning activities. (LRW)

  1. Activation of a human chromosomal replication origin by protein tethering

    PubMed Central

    Chen, Xiaomi; Liu, Guoqi; Leffak, Michael

    2013-01-01

    The specification of mammalian chromosomal replication origins is incompletely understood. To analyze the assembly and activation of prereplicative complexes (pre-RCs), we tested the effects of tethered binding of chromatin acetyltransferases and replication proteins on chromosomal c-myc origin deletion mutants containing a GAL4-binding cassette. GAL4DBD (DNA binding domain) fusions with Orc2, Cdt1, E2F1 or HBO1 coordinated the recruitment of the Mcm7 helicase subunit, the DNA unwinding element (DUE)-binding protein DUE-B and the minichromosome maintenance (MCM) helicase activator Cdc45 to the replicator, and restored origin activity. In contrast, replication protein binding and origin activity were not stimulated by fusion protein binding in the absence of flanking c-myc DNA. Substitution of the GAL4-binding site for the c-myc replicator DUE allowed Orc2 and Mcm7 binding, but eliminated origin activity, indicating that the DUE is essential for pre-RC activation. Additionally, tethering of DUE-B was not sufficient to recruit Cdc45 or activate pre-RCs formed in the absence of a DUE. These results show directly in a chromosomal background that chromatin acetylation, Orc2 or Cdt1 suffice to recruit all downstream replication initiation activities to a prospective origin, and that chromosomal origin activity requires singular DNA sequences. PMID:23658226

  2. Origins.

    PubMed

    Weinberg, S

    1985-10-01

    The farthest of the galaxies that can be seen through the large ground-based telescopes of modern astronomy, such as those on La Palma in the Canary Islands, are so far away that they appear as they did close to the time of the origin of the universe, perhaps some 10 billion years ago. Much has been learned, and much has still to be learned, about the young universe from optical and radio telescopes, but these instruments cannot be used to look directly at the universe in its first few hundred thousand years. Instead, they are used to search the relatively recent past for relics of much earlier times. Together with experiments planned for the next generation of elementary particle accelerators, astronomical observations should continue to extend what is known about the universe backward in time to the Big Bang and may eventually help to reveal the origins of the physical laws that govern the universe. PMID:17817144

  3. [Some features of the relationship between Lullism and pseudo-Lullism in the early modern times].

    PubMed

    López Pérez, Miguel

    2002-01-01

    In this work, the author presents, following a chronologic sequence, some aspects of Llull's image that became controversial during the 16th century, especially the discussion about the idea of Llull as alchemist, which developed around the 16th century. To this end, the author analyses the origin and development of the polemic since the 14th century, including the "official" positions. At the same time, the two positions (Llull the achemist and Llull the philosopher) are related to similar occurrences outside the Iberian Peninsular, especially in France and Italy. PMID:12678049

  4. Step-Dame Study's Purpose: Early Modern Literature and Critical Thinking

    ERIC Educational Resources Information Center

    Isaacson, Emily Ruth

    2013-01-01

    Given what seems a constant barrage of criticism aimed at the academy from politicians and the public--and the great concern for buzz words like accountability and transparency--it has become fairly routine to see a defense of the humanities in opinion pieces in "Inside Higher Education," "The Chronicle of Higher Education," "The New York Times,"…

  5. ‘Nature Concocts & Expels’: The Agents and Processes of Recovery from Disease in Early Modern England

    PubMed Central

    Newton, Hannah

    2015-01-01

    The ‘golden saying’ in early modern medicine was ‘Nature is the healer of disease’. This article uncovers the meaning and significance of this forgotten axiom by investigating perceptions of the agents and physiological processes of recovery from illness in England, c.1580–1720. Drawing on sources such as medical texts and diaries, it shows that doctors and laypeople attributed recovery to three agents—God, Nature and the practitioner. While scholars are familiar with the roles of providence and medicine, the vital agency of Nature has been overlooked. In theory, the agents operated in a hierarchy: Nature was ‘God's instrument’, and the physician, ‘Nature's servant’; but in practice the power balance was more ambivalent. Nature was depicted both as a housewife who cooked and cleaned the humours, and as a warrior who defeated the disease. Through exploring these complex dynamics, the article sheds fresh light on concepts of gender, disease and bodies. PMID:26217069

  6. Origins and early development of human body knowledge.

    PubMed

    Slaughter, Virginia; Heron, Michelle

    2004-01-01

    As a knowable object, the human body is highly complex. Evidence from several converging lines of research, including psychological studies, neuroimaging and clinical neuropsychology, indicates that human body knowledge is widely distributed in the adult brain, and is instantiated in at least three partially independent levels of representation. Sensorimotor body knowledge is responsible for on-line control and movement of one's own body and may also contribute to the perception of others' moving bodies; visuo-spatial body knowledge specifies detailed structural descriptions of the spatial attributes of the human body; and lexical-semantic body knowledge contains language-based knowledge about the human body. In the first chapter of this Monograph, we outline the evidence for these three hypothesized levels of human body knowledge, then review relevant literature on infants' and young children's human body knowledge in terms of the three-level framework. In Chapters II and III, we report two complimentary series of studies that specifically investigate the emergence of visuo-spatial body knowledge in infancy. Our technique is to compare infants'responses to typical and scrambled human bodies, in order to evaluate when and how infants acquire knowledge about the canonical spatial layout of the human body. Data from a series of visual habituation studies indicate that infants first discriminate scrambled from typical human body picture sat 15 to 18 months of age. Data from object examination studies similarly indicate that infants are sensitive to violations of three-dimensional human body stimuli starting at 15-18 months of age. The overall pattern of data supports several conclusions about the early development of human body knowledge: (a) detailed visuo-spatial knowledge about the human body is first evident in the second year of life, (b) visuo-spatial knowledge of human faces and human bodies are at least partially independent in infancy and (c) infants' initial visuo-spatial human body representations appear to be highly schematic, becoming more detailed and specific with development. In the final chapter, we explore these conclusions and discuss how levels of body knowledge may interact in early development. PMID:15317497

  7. The Origins of Human Interaction. The Van Zelst Lecture in Communication.

    ERIC Educational Resources Information Center

    Cappella, Joseph N.

    In the field of communication studies the preeminent forms of explanation of human behavior have been the social and psychological, but biological origins may be as important to understanding human communication as are social origins. Communication research suggests a biological basis for certain patterns of adult interaction. Although these…

  8. [The Significance of Terminology for the Idea of a Historical Period--Considerations on Frühe Neuzeit/Early Modern].

    PubMed

    Nipperdey, Justus

    2015-06-01

    The Significance of Terminology for the Idea of a Historical Period - Considerations on Frühe Neuzeit/Early Modern. This article focuses on the relationship between the names given to historical periods and the attributed substance of that period. It argues that the possibility of a neutralisation in terms of substantive meaning depends on the terminology used to delineate a historical period. Considering the example of 'early modern history' the article sketches the usage of that term in twentieth century historiography. While it is clear that the concept cannot escape the inherent teleology of modernity succeeding pre-modern ages, the analysis shows that historians have used 'early modern' in surprisingly divers ways trying to overcome the semantic meaning of the term itself. PMID:26140628

  9. Recent origin of low trabecular bone density in modern humans.

    PubMed

    Chirchir, Habiba; Kivell, Tracy L; Ruff, Christopher B; Hublin, Jean-Jacques; Carlson, Kristian J; Zipfel, Bernhard; Richmond, Brian G

    2015-01-13

    Humans are unique, compared with our closest living relatives (chimpanzees) and early fossil hominins, in having an enlarged body size and lower limb joint surfaces in combination with a relatively gracile skeleton (i.e., lower bone mass for our body size). Some analyses have observed that in at least a few anatomical regions modern humans today appear to have relatively low trabecular density, but little is known about how that density varies throughout the human skeleton and across species or how and when the present trabecular patterns emerged over the course of human evolution. Here, we test the hypotheses that (i) recent modern humans have low trabecular density throughout the upper and lower limbs compared with other primate taxa and (ii) the reduction in trabecular density first occurred in early Homo erectus, consistent with the shift toward a modern human locomotor anatomy, or more recently in concert with diaphyseal gracilization in Holocene humans. We used peripheral quantitative CT and microtomography to measure trabecular bone of limb epiphyses (long bone articular ends) in modern humans and chimpanzees and in fossil hominins attributed to Australopithecus africanus, Paranthropus robustus/early Homo from Swartkrans, Homo neanderthalensis, and early Homo sapiens. Results show that only recent modern humans have low trabecular density throughout the limb joints. Extinct hominins, including pre-Holocene Homo sapiens, retain the high levels seen in nonhuman primates. Thus, the low trabecular density of the recent modern human skeleton evolved late in our evolutionary history, potentially resulting from increased sedentism and reliance on technological and cultural innovations. PMID:25535354

  10. Recent origin of low trabecular bone density in modern humans

    PubMed Central

    Chirchir, Habiba; Kivell, Tracy L.; Ruff, Christopher B.; Hublin, Jean-Jacques; Carlson, Kristian J.; Zipfel, Bernhard; Richmond, Brian G.

    2015-01-01

    Humans are unique, compared with our closest living relatives (chimpanzees) and early fossil hominins, in having an enlarged body size and lower limb joint surfaces in combination with a relatively gracile skeleton (i.e., lower bone mass for our body size). Some analyses have observed that in at least a few anatomical regions modern humans today appear to have relatively low trabecular density, but little is known about how that density varies throughout the human skeleton and across species or how and when the present trabecular patterns emerged over the course of human evolution. Here, we test the hypotheses that (i) recent modern humans have low trabecular density throughout the upper and lower limbs compared with other primate taxa and (ii) the reduction in trabecular density first occurred in early Homo erectus, consistent with the shift toward a modern human locomotor anatomy, or more recently in concert with diaphyseal gracilization in Holocene humans. We used peripheral quantitative CT and microtomography to measure trabecular bone of limb epiphyses (long bone articular ends) in modern humans and chimpanzees and in fossil hominins attributed to Australopithecus africanus, Paranthropus robustus/early Homo from Swartkrans, Homo neanderthalensis, and early Homo sapiens. Results show that only recent modern humans have low trabecular density throughout the limb joints. Extinct hominins, including pre-Holocene Homo sapiens, retain the high levels seen in nonhuman primates. Thus, the low trabecular density of the recent modern human skeleton evolved late in our evolutionary history, potentially resulting from increased sedentism and reliance on technological and cultural innovations. PMID:25535354

  11. Origins of the Human Pointing Gesture: A Training Study

    ERIC Educational Resources Information Center

    Matthews, Danielle; Behne, Tanya; Lieven, Elena; Tomasello, Michael

    2012-01-01

    Despite its importance in the development of children's skills of social cognition and communication, very little is known about the ontogenetic origins of the pointing gesture. We report a training study in which mothers gave children one month of extra daily experience with pointing as compared with a control group who had extra experience with…

  12. Origins of the Human Pointing Gesture: A Training Study

    ERIC Educational Resources Information Center

    Matthews, Danielle; Behne, Tanya; Lieven, Elena; Tomasello, Michael

    2012-01-01

    Despite its importance in the development of children's skills of social cognition and communication, very little is known about the ontogenetic origins of the pointing gesture. We report a training study in which mothers gave children one month of extra daily experience with pointing as compared with a control group who had extra experience with

  13. Francis Bacon's natural history and the Senecan natural histories of early modern Europe.

    PubMed

    Jalobeanu, Dana

    2012-01-01

    At various stages in his career, Francis Bacon claimed to have reformed and changed traditional natural history in such a way that his new "natural and experimental history" was unlike any of its ancient or humanist predecessors. Surprisingly, such claims have gone largely unquestioned in Baconian scholarship. Contextual readings of Bacon's natural history have compared it, so far, only with Plinian or humanist natural history. This paper investigates a different form of natural history, very popular among Bacon's contemporaries, but yet unexplored by contemporary students of Bacon's works. I have provisionally called this form of natural history'Senecan' natural history, partly because it took shape in the Neo-Stoic revival of the sixteenth-century, partly because it originates in a particular cosmographical reading of Seneca's Naturales quaestiones. I discuss in this paper two examples of Senecan natural history: the encyclopedic and cosmographical projects of Pierre de la Primaudaye (1546-1619) and Samuel Purchas (1577-1626). I highlight a number of similarities between these two projects and Francis Bacon's natural history, and argue that Senecan natural history forms an important aspect in the historical and philosophical background that needs to be taken into consideration if we want to understand the extent to which Bacon's project to reform natural history can be said to be new. PMID:22702172

  14. Out of Africa: modern human origins special feature: the origin of Neandertals.

    PubMed

    Hublin, J J

    2009-09-22

    Western Eurasia yielded a rich Middle (MP) and Late Pleistocene (LP) fossil record documenting the evolution of the Neandertals that can be analyzed in light of recently acquired paleogenetical data, an abundance of archeological evidence, and a well-known environmental context. Their origin likely relates to an episode of recolonization of Western Eurasia by hominins of African origin carrying the Acheulean technology into Europe around 600 ka. An enhancement of both glacial and interglacial phases may have played a crucial role in this event, as well as in the subsequent evolutionary history of the Western Eurasian populations. In addition to climatic adaptations and an increase in encephalization, genetic drift seems to have played a major role in their evolution. To date, a clear speciation event is not documented, and the most likely scenario for the fixation of Neandertal characteristics seems to be an accretion of features along the second half of the MP. Although a separation time for the African and Eurasian populations is difficult to determine, it certainly predates OIS 11 as phenotypic Neandertal features are documented as far back as and possibly before this time. It is proposed to use the term "Homo rhodesiensis" to designate the large-brained hominins ancestral to H. sapiens in Africa and at the root of the Neandertals in Europe, and to use the term "Homo neanderthalensis" to designate all of the specimens carrying derived metrical or non-metrical features used in the definition of the LP Neandertals. PMID:19805257

  15. DNA Replication Origin Interference Increases the Spacing between Initiation Events in Human Cells

    PubMed Central

    Lebofsky, Ronald; Heilig, Roland; Sonnleitner, Max; Weissenbach, Jean

    2006-01-01

    Mammalian DNA replication origins localize to sites that range from base pairs to tens of kilobases. A regular distribution of initiations in individual cell cycles suggests that only a limited number of these numerous potential start sites are converted into activated origins. Origin interference can silence redundant origins; however, it is currently unknown whether interference participates in spacing functional human initiation events. By using a novel hybridization strategy, genomic Morse code, on single combed DNA molecules from primary keratinocytes, we report the initiation sites present on 1.5 Mb of human chromosome 14q11.2. We confirm that initiation zones are widespread in human cells, map to intergenic regions, and contain sequence motifs found at other mammalian initiation zones. Origins used per cell cycle are less abundant than the potential sites of initiation, and their limited use increases the spacing between initiation events. Between-zone interference decreases in proportion to the distance from the active origin, whereas within-zone interference is 100% efficient. These results identify a hierarchical organization of origin activity in human cells. Functional origins govern the probability that nearby origins will fire in the context of multiple potential start sites of DNA replication, and this is mediated by origin interference. PMID:17005913

  16. DNA replication origin interference increases the spacing between initiation events in human cells.

    PubMed

    Lebofsky, Ronald; Heilig, Roland; Sonnleitner, Max; Weissenbach, Jean; Bensimon, Aaron

    2006-12-01

    Mammalian DNA replication origins localize to sites that range from base pairs to tens of kilobases. A regular distribution of initiations in individual cell cycles suggests that only a limited number of these numerous potential start sites are converted into activated origins. Origin interference can silence redundant origins; however, it is currently unknown whether interference participates in spacing functional human initiation events. By using a novel hybridization strategy, genomic Morse code, on single combed DNA molecules from primary keratinocytes, we report the initiation sites present on 1.5 Mb of human chromosome 14q11.2. We confirm that initiation zones are widespread in human cells, map to intergenic regions, and contain sequence motifs found at other mammalian initiation zones. Origins used per cell cycle are less abundant than the potential sites of initiation, and their limited use increases the spacing between initiation events. Between-zone interference decreases in proportion to the distance from the active origin, whereas within-zone interference is 100% efficient. These results identify a hierarchical organization of origin activity in human cells. Functional origins govern the probability that nearby origins will fire in the context of multiple potential start sites of DNA replication, and this is mediated by origin interference. PMID:17005913

  17. The diverse origins of the human gene pool.

    PubMed

    Pääbo, Svante

    2015-06-01

    Analyses of the genomes of Neanderthals and Denisovans, the closest evolutionary relatives of present-day humans, suggest that our ancestors were part of a web of now-extinct populations linked by limited, but intermittent or sometimes perhaps even persistent, gene flow. PMID:25982166

  18. Spatial dynamics of human-origin H1 influenza A v irus in North American swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The emergence and rapid global spread of the swine-origin H1N1/09 pandemic influenza A virus in humans underscores the importance of swine populations as reservoirs for genetically diverse influenza viruses with the potential to infect humans. However, despite their significance for animal and human...

  19. The human socio-cognitive niche and its evolutionary origins

    PubMed Central

    Whiten, Andrew; Erdal, David

    2012-01-01

    Hominin evolution took a remarkable pathway, as the foraging strategy extended to large mammalian prey already hunted by a guild of specialist carnivores. How was this possible for a moderately sized ape lacking the formidable anatomical adaptations of these competing ‘professional hunters’? The long-standing answer that this was achieved through the elaboration of a new ‘cognitive niche’ reliant on intelligence and technology is compelling, yet insufficient. Here we present evidence from a diversity of sources supporting the hypothesis that a fuller answer lies in the evolution of a new socio-cognitive niche, the principal components of which include forms of cooperation, egalitarianism, mindreading (also known as ‘theory of mind’), language and cultural transmission, that go far beyond the most comparable phenomena in other primates. This cognitive and behavioural complex allows a human hunter–gatherer band to function as a unique and highly competitive predatory organism. Each of these core components of the socio-cognitive niche is distinctive to humans, but primate research has increasingly identified related capacities that permit inferences about significant ancestral cognitive foundations to the five pillars of the human social cognitive niche listed earlier. The principal focus of the present study was to review and integrate this range of recent comparative discoveries. PMID:22734055

  20. The human socio-cognitive niche and its evolutionary origins.

    PubMed

    Whiten, Andrew; Erdal, David

    2012-08-01

    Hominin evolution took a remarkable pathway, as the foraging strategy extended to large mammalian prey already hunted by a guild of specialist carnivores. How was this possible for a moderately sized ape lacking the formidable anatomical adaptations of these competing 'professional hunters'? The long-standing answer that this was achieved through the elaboration of a new 'cognitive niche' reliant on intelligence and technology is compelling, yet insufficient. Here we present evidence from a diversity of sources supporting the hypothesis that a fuller answer lies in the evolution of a new socio-cognitive niche, the principal components of which include forms of cooperation, egalitarianism, mindreading (also known as 'theory of mind'), language and cultural transmission, that go far beyond the most comparable phenomena in other primates. This cognitive and behavioural complex allows a human hunter-gatherer band to function as a unique and highly competitive predatory organism. Each of these core components of the socio-cognitive niche is distinctive to humans, but primate research has increasingly identified related capacities that permit inferences about significant ancestral cognitive foundations to the five pillars of the human social cognitive niche listed earlier. The principal focus of the present study was to review and integrate this range of recent comparative discoveries. PMID:22734055

  1. The origin of remarkable resilience of human tooth enamel

    NASA Astrophysics Data System (ADS)

    Zhao, Xiaoli; O'Brien, Simona; Shaw, Jeremy; Abbott, Paul; Munroe, Paul; Habibi, Daryoush; Xie, Zonghan

    2013-12-01

    The mechanical properties of human tooth enamel depend not only on test locations but also on the indentation depth. However, it remains uncertain what roles the depth-dependant properties play in mechanical performance of enamel. Here we reveal that a change in the mechanical properties of enamel, in particular its strength, with increasing indentation depth promotes inelastic deformation in material. In doing so, the severity and extent of stress concentration is reduced. Furthermore, we observed that following unloading, self-recovery occurs in enamel. These findings improve our understanding of the underlying mechanisms responsible for the remarkable resilience of enamel.

  2. Thinking with the saint: the miracle of Saint Januarius of Naples and science in early modern Europe.

    PubMed

    de Ceglia, Francesco Paolo

    2014-01-01

    The aim of this paper is to reconstruct the way in which early modem science questioned and indirectly influenced (while being in its turn influenced by) the conceptualization of the liquefaction of the blood of Saint Januarius, a phenomenon that has been taking place at regular intervals in Naples since the late Middle Ages. In the seventeenth century, a debate arose that divided Europe between supporters of a theory of divine intervention and believers in the occult properties of the blood. These two theoretical options reflected two different perspectives on the relationship between the natural and the supernatural. While in the seventeenth century, the emphasis was placed on the predictable periodicity of the miraculous event of liquefaction as a manifestation of God in his role as a divine regulator, in the eighteenth century the event came to be described as capricious and unpredictable, in an attempt to differentiate miracles from the workings of nature, which were deemed to be normative. The miracle of the blood of Saint Januarius thus provides a window through which we can catch a glimpse of how the natural order was perceived in early modern Europe at a time when the Continent was culturally fragmented into north and south, Protestantism and Catholicism, learned and ignorant. PMID:25080643

  3. Origins of the human pointing gesture: a training study.

    PubMed

    Matthews, Danielle; Behne, Tanya; Lieven, Elena; Tomasello, Michael

    2012-11-01

    Despite its importance in the development of children's skills of social cognition and communication, very little is known about the ontogenetic origins of the pointing gesture. We report a training study in which mothers gave children one month of extra daily experience with pointing as compared with a control group who had extra experience with musical activities. One hundred and two infants of 9, 10, or 11 months of age were seen at the beginning, middle, and end of this one-month period and tested for declarative pointing and gaze following. Infants'ability to point with the index finger at the end of the study was not affected by the training but was instead predicted by infants' prior ability to follow the gaze direction of an adult. The frequency with which infants pointed indexically was also affected by infant gaze following ability and, in addition, by maternal pointing frequency in free play, but not by training. In contrast, infants' ability to monitor their partner's gaze when pointing, and the frequency with which they did so, was affected by both training and maternal pointing frequency in free play. These results suggest that prior social cognitive advances, rather than adult socialization of pointing per se, determine the developmental onset of indexical pointing, but socialization processes such as imitation and adult shaping subsequently affect both infants' ability to monitor their interlocutor's gaze while they point and how frequently infants choose to point. PMID:23106736

  4. Ape parasite origins of human malaria virulence genes

    PubMed Central

    Larremore, Daniel B.; Sundararaman, Sesh A.; Liu, Weimin; Proto, William R.; Clauset, Aaron; Loy, Dorothy E.; Speede, Sheri; Plenderleith, Lindsey J.; Sharp, Paul M.; Hahn, Beatrice H.; Rayner, Julian C.; Buckee, Caroline O.

    2015-01-01

    Antigens encoded by the var gene family are major virulence factors of the human malaria parasite Plasmodium falciparum, exhibiting enormous intra- and interstrain diversity. Here we use network analysis to show that var architecture and mosaicism are conserved at multiple levels across the Laverania subgenus, based on var-like sequences from eight single-species and three multi-species Plasmodium infections of wild-living or sanctuary African apes. Using select whole-genome amplification, we also find evidence of multi-domain var structure and synteny in Plasmodium gaboni, one of the ape Laverania species most distantly related to P. falciparum, as well as a new class of Duffy-binding-like domains. These findings indicate that the modular genetic architecture and sequence diversity underlying var-mediated host-parasite interactions evolved before the radiation of the Laverania subgenus, long before the emergence of P. falciparum. PMID:26456841

  5. Ape parasite origins of human malaria virulence genes.

    PubMed

    Larremore, Daniel B; Sundararaman, Sesh A; Liu, Weimin; Proto, William R; Clauset, Aaron; Loy, Dorothy E; Speede, Sheri; Plenderleith, Lindsey J; Sharp, Paul M; Hahn, Beatrice H; Rayner, Julian C; Buckee, Caroline O

    2015-01-01

    Antigens encoded by the var gene family are major virulence factors of the human malaria parasite Plasmodium falciparum, exhibiting enormous intra- and interstrain diversity. Here we use network analysis to show that var architecture and mosaicism are conserved at multiple levels across the Laverania subgenus, based on var-like sequences from eight single-species and three multi-species Plasmodium infections of wild-living or sanctuary African apes. Using select whole-genome amplification, we also find evidence of multi-domain var structure and synteny in Plasmodium gaboni, one of the ape Laverania species most distantly related to P. falciparum, as well as a new class of Duffy-binding-like domains. These findings indicate that the modular genetic architecture and sequence diversity underlying var-mediated host-parasite interactions evolved before the radiation of the Laverania subgenus, long before the emergence of P. falciparum. PMID:26456841

  6. Environmental extremes: origins, consequences and amelioration in humans.

    PubMed

    Tipton, M J

    2016-01-01

    Professor Sir George Lindor Brown (1903-1971) is known for his pioneering research into cholinergic neuromuscular transmission. However, during World War II he worked in hyperbaric physiology, and his research into underwater physiology greatly improved the safety of divers. It is perhaps fitting, therefore, that this review, which accompanies the Physiological Society's G. L. Brown Prize Lecture for 2015, explores the impact and mitigation of the environmental stresses which, to varying extents, have shaped our past, threaten our present and inform our future. From a whole-body, integrative perspective, this review examines our current understanding of microgravity, hypo- and hyperbaria, heat, cold air and cold water as both individual and combined stresses. Consideration is given to ways of mitigating the threat posed by environmental extremes, including the differing extents to which humans can demonstrate adaptation to them. Finally, recommendations for further study are suggested that might result in both direct and indirect insights. PMID:26391095

  7. Human physiological reaction to geomagnetic disturbances of solar origin

    NASA Astrophysics Data System (ADS)

    Dimitrova, Sv.; Stoilova, I.

    2002-12-01

    During the last two decades publications about the influence of geomagnetic activity on human health increase but there are not still strong evidences for this relationship. We performed measurements and observations of 86 working volunteers during the period of autumn and spring equinox. We examined systolic, diastolic blood pressure and pulse rate. We also collected data for some personal health condition complaints. Four-way analyses of variance (MANOVA method) were employed and the influence of factors geomagnetic activity level, sequence of the days of measurements with respect to the increased geomagnetic activity, medicaments and sex was investigated. We also performed three-way analyses of variance and investigated influence of atmospheric pressure, medicaments and sex on the physiological parameters under consideration. Our investigations indicate that most of the persons examined irrespectively to their health status could be sensitive to the geomagnetic changes, which influence directly self-confidence and working ability.

  8. Mutational Heterogeneity in Human Cancers: Origin and Consequences

    PubMed Central

    Salk, Jesse J.; Fox, Edward J.; Loeb, Lawrence A.

    2012-01-01

    Cancer recapitulates Darwinian evolution. Mutations acquired during life that provide cells with a growth or survival advantage will preferentially multiply to form a tumor. As a result of The Cancer Genome Atlas project we have now gathered detailed information on the nucleotide sequence changes in a number of human cancers. The sources of mutations in cancer are diverse and the complexity of those found to be clonally present in tumors has increasingly made it difficult to identify key rate-limiting genes for tumor growth that might serve as potential targets for directed therapies. The impact of DNA sequencing on future cancer research and personalized therapy is likely to be profound and merits critical evaluation. PMID:19743960

  9. Coevolution between human's anticancer activities and functional foods from crop origin center in the world.

    PubMed

    Zeng, Ya-Wen; Du, Juan; Pu, Xiao-Ying; Yang, Jia-Zhen; Yang, Tao; Yang, Shu-Ming; Yang, Xiao-Meng

    2015-01-01

    Cancer is the leading cause of death around the world. Anticancer activities from many functional food sources have been reported in years, but correlation between cancer prevalence and types of food with anticancer activities from crop origin center in the world as well as food source with human migration are unclear. Hunger from food shortage is the cause of early human evolution from Africa to Asia and later into Eurasia. The richest functional foods are found in crop origin centers, housing about 70% in the world populations. Crop origin centers have lower cancer incidence and mortality in the world, especially Central Asia, Middle East, Southwest China, India and Ethiopia. Asia and Africa with the richest anticancer crops is not only the most important evolution base of humans and origin center of anticancer functional crop, but also is the lowest mortality and incidence of cancers in the world. Cancer prevention of early human migrations was associated with functional foods from crop origin centers, especially Asia with four centers and one subcenter of crop origin, accounting for 58% of the world population. These results reveal that coevolution between human's anticancer activities associated with functional foods for crop origin centers, especially in Asia and Africa. PMID:25824728

  10. Immunocompetent cells in uterine cervical lesions of human papillomavirus origin.

    PubMed

    Syrjänen, K J

    1983-01-01

    To elucidate the local immunological reactions operative in the human papillomavirus (HPV)-induced lesions of the uterine cervix, a total of 150 cervical biopsies containing a dysplastic or a neoplastic change with (CO, 97 cases) or without (NCO, 53 cases) a coexistent HPV lesion (a flat, an inverted or a papillomatous condyloma) were subjected to ANAE (acid alpha-naphthyl acetate esterase) staining of the immunocompetent cells; B and T lymphocytes, mononuclear phagocytes (MPS cells). In addition, HPV antigens were demonstrated by an indirect immunoperoxidase-PAP method. Age of the patients did not influence the proportions of B, T and MPS cells. Degree of epithelial atypia was inversely related to proportion of B cells in NCO but not in CO series, and directly related to proportions of T cells in CO series, the latter T cell increase being most probably ascribable to the appearance of suppressor T cells. Unlike in the different types of skin warts (caused by divergent HPV types), the type of the cervical condyloma did not affect the proportions of B, T and MPS cells, suggesting a common HPV type as a causative agent of the latter. MPS and T cells were more numerous in HPV-positive condylomas than in HPV-negative ones, supporting the concept that cell-mediated immune mechanisms recognize the surface antigens of the virus-transformed cells coded by the viral genome in the host cell nuclei (HPV+). The findings are discussed in terms of the immune mechanisms involved in rejection of HPV lesions in general, and those of the uterine cervix especially. The full significance of these mechanisms can only be understood when adequate follow-up data of the lesions are at hand. PMID:6317528

  11. Three days in October of 1630: detailed examination of mortality during an early modern plague epidemic in Venice.

    PubMed

    Ell, S R

    1989-01-01

    The epidemiology of medieval and early modern European plague remains highly controversial. It now seems likely that the epidemiology was not uniform throughout either the geographic or temporal boundaries of the plague in Western Europe. The Venetian plague of 1630 was extensively documented; day-by-day records were kept, and each mortality in the city was recorded in a set format. The days 23-25 October 1630, representing a period when mortality was beginning to increase sharply, are examined. In all, 1,163 deaths were recorded. They show a large preponderance of women; a mean age of 28, but a majority of cases clumped between ages 0 and 25 years; and an unequal sex ratio among children. Further, there was an identifiable smallpox epidemic raging simultaneously with plague, and more than one-quarter of all the deaths in this period of high mortality were clearly due to nonplague causes. Deaths due to wounds and associated with violence were prominent in one parish, which suggests that in times of plague the breakdown in the normal machinery of government, in everyday patterns of life, and possibly of mental well being resulted in an even more exaggerated death toll. These factors--violence, accidents, and other epidemics--have never been so definitively tied to a European plague epidemic. In addition, there are hints that plague has a marked proclivity to kill pregnant women--their deaths far outnumber those anticipated--and that plague was very localized at a given moment within Venice itself, even during times of peak mortality. PMID:2644686

  12. ‘Very Sore Nights and Days’: The Child’s Experience of Illness in Early Modern England, c.1580–1720

    PubMed Central

    NEWTON, HANNAH

    2011-01-01

    Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife. PMID:21461308

  13. Circles of Confidence in Correspondence: Modeling Confidentiality and Secrecy in Knowledge Exchange Networks of Letters and Drawings in the Early Modern Period.

    PubMed

    van den Heuvel, Charles; Weingart, Scott B; Spelt, Nils; Nellen, Henk

    2016-01-01

    Science in the early modern world depended on openness in scholarly communication. On the other hand, a web of commercial, political, and religious conflicts required broad measures of secrecy and confidentiality; similar measures were integral to scholarly rivalries and plagiarism. This paper analyzes confidentiality and secrecy in intellectual and technological knowledge exchange via letters and drawings. We argue that existing approaches to understanding knowledge exchange in early modern Europe--which focus on the Republic of Letters as a unified entity of corresponding scholars--can be improved upon by analyzing multilayered networks of communication. We describe a data model to analyze circles of confidence and cultures of secrecy in intellectual and technological knowledge exchanges. Finally, we discuss the outcomes of a first experiment focusing on the question of how personal and professional/official relationships interact with confidentiality and secrecy, based on a case study of the correspondence of Hugo Grotius. PMID:27071301

  14. Human microRNAs originated from two periods at accelerated rates in mammalian evolution.

    PubMed

    Iwama, Hisakazu; Kato, Kiyohito; Imachi, Hitomi; Murao, Koji; Masaki, Tsutomu

    2013-03-01

    MicroRNAs (miRNAs) are short, noncoding RNAs that modulate genes posttranscriptionally. Frequent gains and losses of miRNA genes have been reported to occur during evolution. However, little is known systematically about the periods of evolutionary origin of the present miRNA gene repertoire of an extant mammalian species. Thus, in this study, we estimated the evolutionary periods during which each of 1,433 present human miRNA genes originated within 15 periods, from human to platypus-human common ancestral branch and a class "conserved beyond theria," primarily using multiple genome alignments of 38 species, plus the pairwise genome alignments of five species. The results showed two peak periods in which the human miRNA genes originated at significantly accelerated rates. The most accelerated rate appeared in the period of the initial phase of hominoid lineage, and the second appeared shortly before Laurasiatherian divergence. Approximately 53% of the present human miRNA genes have originated within the simian lineage to human. In particular, approximately 28% originated within the hominoid lineage. The early phase of placental mammal radiation comprises approximately 28%, while no more than 15% of human miRNAs have been conserved beyond placental mammals. We also clearly showed a general trend, in which the miRNA expression level decreases as the miRNA becomes younger. Intriguingly, amid this decreasing trend of expression, we found one significant rise in the expression level that corresponded to the initial phase of the hominoid lineage, suggesting that increased functional acquisitions of miRNAs originated at this particular period. PMID:23171859

  15. Human MicroRNAs Originated from Two Periods at Accelerated Rates in Mammalian Evolution

    PubMed Central

    Iwama, Hisakazu; Kato, Kiyohito; Imachi, Hitomi; Murao, Koji; Masaki, Tsutomu

    2013-01-01

    MicroRNAs (miRNAs) are short, noncoding RNAs that modulate genes posttranscriptionally. Frequent gains and losses of miRNA genes have been reported to occur during evolution. However, little is known systematically about the periods of evolutionary origin of the present miRNA gene repertoire of an extant mammalian species. Thus, in this study, we estimated the evolutionary periods during which each of 1,433 present human miRNA genes originated within 15 periods, from human to platypus–human common ancestral branch and a class “conserved beyond theria,” primarily using multiple genome alignments of 38 species, plus the pairwise genome alignments of five species. The results showed two peak periods in which the human miRNA genes originated at significantly accelerated rates. The most accelerated rate appeared in the period of the initial phase of hominoid lineage, and the second appeared shortly before Laurasiatherian divergence. Approximately 53% of the present human miRNA genes have originated within the simian lineage to human. In particular, approximately 28% originated within the hominoid lineage. The early phase of placental mammal radiation comprises approximately 28%, while no more than 15% of human miRNAs have been conserved beyond placental mammals. We also clearly showed a general trend, in which the miRNA expression level decreases as the miRNA becomes younger. Intriguingly, amid this decreasing trend of expression, we found one significant rise in the expression level that corresponded to the initial phase of the hominoid lineage, suggesting that increased functional acquisitions of miRNAs originated at this particular period. PMID:23171859

  16. In Vivo Liver Regeneration Potential of Human Induced Pluripotent Stem Cells from Diverse Origins

    PubMed Central

    Liu, Hua; Kim, Yonghak; Sharkis, Saul; Marchionni, Luigi; Jang, Yoon-Young

    2012-01-01

    Human induced pluripotent stem cells (iPSCs) are a potential source of hepatocytes for liver transplantation to treat end-stage liver disease. In vitro differentiation of human iPSCs into hepatic cells has been achieved using a multistage differentiation protocol, but whether these cells are functional and capable of engrafting and regenerating diseased liver tissue is not clear. We show that human iPSC-derived hepatic cells at various differentiation stages can engraft the liver in a mouse transplantation model. Using the same differentiation and transplantation protocols, we also assessed the ability of human iPSCs derived from each of the three developmental germ layer tissues (that is, ectoderm, mesoderm, and endoderm) to regenerate mouse liver. These iPSC lines, with similar but distinct global DNA methylation patterns, differentiated into multistage hepatic cells with an efficiency similar to that of human embryonic stem cells. Human hepatic cells at various differentiation stages derived from iPSC lines of different origins successfully repopulated the liver tissue of mice with liver cirrhosis. They also secreted human-specific liver proteins into mouse blood at concentrations comparable to that of proteins secreted by human primary hepatocytes. Our results demonstrate the engraftment and liver regenerative capabilities of human iPSC-derived multistage hepatic cells in vivo and suggest that human iPSCs of distinct origins and regardless of their parental epigenetic memory can efficiently differentiate along the hepatic lineage. PMID:21562231

  17. Mitochondrial DNA sequences in ancient Australians: Implications for modern human origins

    PubMed Central

    Adcock, Gregory J.; Dennis, Elizabeth S.; Easteal, Simon; Huttley, Gavin A.; Jermiin, Lars S.; Peacock, W. James; Thorne, Alan

    2001-01-01

    DNA from ancient human remains provides perspectives on the origin of our species and the relationship between molecular and morphological variation. We report analysis of mtDNA from the remains of 10 ancient Australians. These include the morphologically gracile Lake Mungo 3 [≈60 thousand years (ka) before present] and three other gracile individuals from Holocene deposits at Willandra Lakes (<10 ka), all within the skeletal range of living Australians, and six Pleistocene/early Holocene individuals (15 to <8 ka) from Kow Swamp with robust morphologies outside the skeletal range of contemporary indigenous Australians. Lake Mungo 3 is the oldest (Pleistocene) “anatomically modern” human from whom DNA has been recovered. His mtDNA belonged to a lineage that only survives as a segment inserted into chromosome 11 of the nuclear genome, which is now widespread among human populations. This lineage probably diverged before the most recent common ancestor of contemporary human mitochondrial genomes. This timing of divergence implies that the deepest known mtDNA lineage from an anatomically modern human occurred in Australia; analysis restricted to living humans places the deepest branches in East Africa. The other ancient Australian individuals we examined have mtDNA sequences descended from the most recent common ancestor of living humans. Our results indicate that anatomically modern humans were present in Australia before the complete fixation of the mtDNA lineage now found in all living people. Sequences from additional ancient humans may further challenge current concepts of modern human origins. PMID:11209053

  18. [Human origin and evolution. A review of advances in paleoanthropology, comparative genetics, and evolutionary psychology].

    PubMed

    Markov, A V

    2009-01-01

    In his main work, "On the origin of species", Darwin has refrained from discusion of the origin of man; be only mentioned that his theory would "throw light" on this problem. This famous Darwin's phrase turned out to be one of the most succesful scientific predictions. In the present paper some of the most important recent adavnces in paleoanthroplogy, comparative genetics and evolutionary psychology are reviewed. These three disciplines currently contribute most to our knowledge of anthropogenesis. The review demonstrates that Darwin's ideas not only "threw light" on human origin and evolution; they provided a comprehensive framework for a great variety of studies concerning different aspects of anthropogenesis. PMID:19891409

  19. Specific and cross-reacting antigens of Staphylococcus aureus of human and canine origins.

    PubMed Central

    Live, I

    1985-01-01

    Biotype -specificity of Staphylococcus aureus of human and canine origins has been found to be associated with thermolabile agglutinogens represented in S. aureus strains 17 and 61218, respectively. Both strains also have exhibited a common thermostable antigen. On that basis, absorbed antisera have been developed for the differentiation of S. aureus of the two biotypes. In the present study, still another thermostable agglutinogen was established, shared by strain 17 and some S. aureus strains of canine origin, as represented by S. aureus strain 887. These findings led to modification and enhanced specificity of the serological method of distinguishing S. aureus of the human biotype from S. aureus of the canine biotype. PMID:2578480

  20. Introductions and Evolution of Human-Origin Seasonal Influenza A Viruses in Multinational Swine Populations

    PubMed Central

    Wentworth, David E.; Culhane, Marie R.; Vincent, Amy L.; Viboud, Cecile; LaPointe, Matthew P.; Lin, Xudong; Holmes, Edward C.; Detmer, Susan E.

    2014-01-01

    ABSTRACT The capacity of influenza A viruses to cross species barriers presents a continual threat to human and animal health. Knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. We sequenced the genomes of 141 influenza viruses collected from North American swine during 2002 to 2011 and identified a swine virus that possessed all eight genome segments of human seasonal A/H3N2 virus origin. A molecular clock analysis indicates that this virus—A/sw/Saskatchewan/02903/2009(H3N2)—has likely circulated undetected in swine for at least 7 years. For historical context, we performed a comprehensive phylogenetic analysis of an additional 1,404 whole-genome sequences from swine influenza A viruses collected globally during 1931 to 2013. Human-to-swine transmission occurred frequently over this time period, with 20 discrete introductions of human seasonal influenza A viruses showing sustained onward transmission in swine for at least 1 year since 1965. Notably, human-origin hemagglutinin (H1 and H3) and neuraminidase (particularly N2) segments were detected in swine at a much higher rate than the six internal gene segments, suggesting an association between the acquisition of swine-origin internal genes via reassortment and the adaptation of human influenza viruses to new swine hosts. Further understanding of the fitness constraints on the adaptation of human viruses to swine, and vice versa, at a genomic level is central to understanding the complex multihost ecology of influenza and the disease threats that swine and humans pose to each other. IMPORTANCE The swine origin of the 2009 A/H1N1 pandemic virus underscored the importance of understanding how influenza A virus evolves in these animals hosts. While the importance of reassortment in generating genetically diverse influenza viruses in swine is well documented, the role of human-to-swine transmission has not been as intensively studied. Through a large-scale sequencing effort, we identified a novel influenza virus of wholly human origin that has been circulating undetected in swine for at least 7 years. In addition, we demonstrate that human-to-swine transmission has occurred frequently on a global scale over the past decades but that there is little persistence of human virus internal gene segments in swine. PMID:24965467

  1. The Role of Transposable Elements in the Origin and Evolution of MicroRNAs in Human

    PubMed Central

    Qin, Sheng; Jin, Ping; Zhou, Xue; Chen, Liming; Ma, Fei

    2015-01-01

    MicroRNAs (miRNAs) are crucial regulators of gene expression at the post-transcriptional level in eukaryotes via targeting gene 3'-untranslated regions. Transposable elements (TEs) are considered as natural origins of some miRNAs. However, what miRNAs are and how these miRNAs originate and evolve from TEs remain unclear. We identified 409 TE-derived miRNAs (386 overlapped with TEs and 23 un-overlapped with TEs) which are derived from TEs in human. This indicates that the TEs play important roles in origin of miRNAs in human. In addition, we found that the proportions of miRNAs derived from TEs (MDTEs) in human are more than other vertebrates especially non-mammal vertebrates. Furthermore, we classified MDTEs into three types and found that TE head or tail sequences along with adjacent genomic sequences contribute to generation of human miRNAs. Our current study will improve the understanding of origin and evolution of human miRNAs. PMID:26115450

  2. Human origin for livestock-associated methicillin-resistant Staphylococcus aureus.

    PubMed

    Fitzgerald, J Ross

    2012-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of human morbidity and mortality worldwide. The emergence in the last decade of a livestock-associated MRSA (LA-MRSA) clone which also has the capacity to cause zoonotic infections in humans has raised important questions regarding its origin and its potential to cause human epidemics. An important study by L. B. Price et al. [mBio 3(1):e00305-11, 2012] provides evidence for a human ancestral origin for LA-MRSA, raising concerns about agricultural practices that may have contributed to its emergence and expansion. The study highlights the potential for comparative whole-genome sequencing of closely related strains to provide valuable insights into the evolutionary history of bacterial pathogens. PMID:22511352

  3. Can ends justify the means? Digging deep for human fusion genes of prokaryotic origin.

    PubMed

    Yiting, Yu; Chaturvedi, Iti; Meow, Liew Kim; Kangueane, Pandjassarame; Sakharkar, Meena Kishore

    2004-09-01

    Gene fusion has been described as an important evolutionary phenomenon. This report focuses on identifying, analyzing, and tabulating human fusion proteins of prokaryotic origin. These fusion proteins are found to mimic operons, simulate protein-protein interfaces in prokaryotes, exhibiting multiple functions and alternative splicing in humans. The accredited biological functions for each of these proteins is made available as a database at http://sege.ntu.edu.sg/wester/fusion/ PMID:15353329

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

    PubMed

    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. PMID:25697304

  5. Sensitivity to Differences in the Motor Origin of Drawings: From Human to Robot

    PubMed Central

    De Preester, Helena; Tsakiris, Manos

    2014-01-01

    This study explores the idea that an observer is sensitive to differences in the static traces of drawings that are due to differences in motor origin. In particular, our aim was to test if an observer is able to discriminate between drawings made by a robot and by a human in the case where the drawings contain salient kinematic cues for discrimination and in the case where the drawings only contain more subtle kinematic cues. We hypothesized that participants would be able to correctly attribute the drawing to a human or a robot origin when salient kinematic cues are present. In addition, our study shows that observers are also able to detect the producer behind the drawings in the absence of these salient kinematic cues. The design was such that in the absence of salient kinematic cues, the drawings are visually very similar, i.e. only differing in subtle kinematic differences. Observers thus had to rely on these subtle kinematic differences in the line trajectories between drawings. However, not only motor origin (human versus robot) but also motor style (natural versus mechanic) plays a role in attributing a drawing to the correct producer, because participants scored less high when the human hand draws in a relatively mechanical way. Overall, this study suggests that observers are sensitive to subtle kinematic differences between visually similar marks in drawings that have a different motor origin. We offer some possible interpretations inspired by the idea of “motor resonance”. PMID:25014198

  6. Rural origin, age, and endoparasite fecal prevalence in dogs surrendered to the Regina Humane Society, 2013

    PubMed Central

    Schurer, Janna M.; Hamblin, Brie; Davenport, Laura; Wagner, Brent; Jenkins, Emily J.

    2014-01-01

    We report the results of fecal parasite surveillance in dogs surrendered to the Regina Humane Society, Saskatchewan, Canada, between May and November 2013. Overall, 23% of 231 dogs were infected with at least 1 intestinal parasite. Endoparasite infection was positively associated with rural origin (P = 0.002) and age (< 12 months; P < 0.001). PMID:25477549

  7. A sequence of tests of minute human blood stains for human origin identification and ABO blood grouping.

    PubMed

    Tokiwa, K

    1986-01-01

    A series of examinations is presented for human origin identification and ABO blood grouping of doubtful minute human blood stains. A blood-stained thread (0.5 cm in length) was first tested to identify human origin by microprecipitation method and then the ABO blood type was determined by both a modified absorption-elution test and a modified mixed agglutination. In the continuous tests, the maximum limits of positive reactions of the microprecipitation method, the modified absorption-elution test, and the modified mixed agglutination were 1:640, 1:160, and 1:2,560 diluted blood, respectively. A and B agglutinogens were more sensitively determined than H agglutinogen. Hemagglutinogens of blood stains on cotton threads were more easily detected than those of polyester ones. PMID:3825313

  8. Identification of the in vivo and in vitro origin of transcription in human rDNA.

    PubMed Central

    Miesfeld, R; Arnheim, N

    1982-01-01

    A Hela cell /-100 extract primed with a purified human rDNA containing clone, has been shown to be capable of initiating specific alpha-amanitin-resistant RNA transcripts. By using a number of truncated templates, the site of RNA polymerase I initiation in vitro has been identified. The origin of transcription in vitro and in vivo was further defined by S1-mapping studies with total Hela cell RNA or RNA isolated from the in vitro transcription reaction. The initiation site was found to be the same. The nucleotide sequence of an 848 bp region around the initiation site, has also been determined. A perfect 15 bp homology has been found to exist between human and mouse rDNA very close to the origin of transcription, although little homology exists elsewhere. Sequences homologous to the origin of transcription region were not found repeated within a 12 kb non-transcribed spacer segment upstream from it. Images PMID:6287426

  9. Dating the origin and dispersal of Human Papillomavirus type 16 on the basis of ancestral human migrations.

    PubMed

    Zehender, Gianguglielmo; Frati, Elena Rosanna; Martinelli, Marianna; Bianchi, Silvia; Amendola, Antonella; Ebranati, Erika; Ciccozzi, Massimo; Galli, Massimo; Lai, Alessia; Tanzi, Elisabetta

    2016-04-01

    A major limitation when reconstructing the origin and evolution of HPV-16 is the lack of reliable substitution rate estimates for the viral genes. On the basis of the hypothesis of human HPV-16 co-divergence, we estimated a mean evolutionary rate of 1.47×10(-7) (95% HPD=0.64-2.47×10(-7)) subs/site/year for the viral LCR region. The results of a Bayesian phylogeographical analysis suggest that the currently circulating HPV-16 most probably originated in Africa about 110 thousand years ago (Kya), before giving rise to four known geographical lineages: the Asian/European lineage, which most probably originated in Asia a mean 38Kya, and the Asian/American and two African lineages, which probably respectively originated about 33 and 27Kya. These data closely reflect current hypotheses concerning modern human expansion based on studies of mitochondrial DNA phylogeny. The correlation between ancient human migration and the present HPV phylogeny may be explained by the co-existence of modes of transmission other than sexual transmission. PMID:26827632

  10. Livestock Origin for a Human Pandemic Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus

    PubMed Central

    Spoor, Laura E.; McAdam, Paul R.; Weinert, Lucy A.; Rambaut, Andrew; Hasman, Henrik; Aarestrup, Frank M.; Kearns, Angela M.; Larsen, Anders R.; Skov, Robert L.; Fitzgerald, J. Ross

    2013-01-01

    ABSTRACT The importance of livestock as a source of bacterial pathogens with the potential for epidemic spread in human populations is unclear. In recent years, there has been a global increase in community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections of healthy humans, but an understanding of the different evolutionary origins of CA-MRSA clones and the basis for their recent expansion is lacking. Here, using a high-resolution phylogenetic approach, we report the discovery of two emergent clones of human epidemic CA-MRSA which resulted from independent livestock-to-human host jumps by the major bovine S.aureus complex, CC97. Of note, one of the new clones was isolated from human infections on four continents, demonstrating its global dissemination since the host jump occurred over 40years ago. The emergence of both human S.aureus clones coincided with the independent acquisition of mobile genetic elements encoding antimicrobial resistance and human-specific mediators of immune evasion, consistent with an important role for these genetic events in the capacity to survive and transmit among human populations. In conclusion, we provide evidence that livestock represent a reservoir for the emergence of new human-pathogenic S.aureus clones with the capacity for pandemic spread. These findings have major public health implications highlighting the importance of surveillance for early identification of emergent clones and improved transmission control measures at the human-livestock interface. PMID:23943757

  11. Sinanthropus in Britain: human origins and international science, 1920-1939.

    PubMed

    Manias, Chris

    2015-06-01

    The Peking Man fossils discovered at Zhoukoudian in north-east China in the 1920s and 1930s were some of the most extensive palaeoanthropological finds of the twentieth century. This article examines their publicization and discussion in Britain, where they were engaged with by some of the world's leading authorities in human evolution, and a media and public highly interested in human-origins research. This international link - simultaneously promoted by scientists in China and in Britain itself - reflected wider debates on international networks; the role of science in the modern world; and changing definitions of race, progress and human nature. This article illustrates how human-origins research was an important means of binding these areas together and presenting scientific work as simultaneously authoritative and credible, but also evoking mystery and adventurousness. Examining this illustrates important features of contemporary views of both science and human development, showing not only the complexities of contemporary regard for the international and public dynamics of scientific research, but wider concerns over human nature, which oscillated between optimistic notions of unity and progress and pessimistic ones of essential differences and misdirected development. PMID:25921683

  12. Phylogenetic inference of the porcine Rotavirus A origin of the human G1 VP7 gene.

    PubMed

    Do, Loan Phuong; Nakagomi, Toyoko; Otaki, Hiroki; Agbemabiese, Chantal Ama; Nakagomi, Osamu; Tsunemitsu, Hiroshi

    2016-06-01

    Rotavirus A (RVA) is an important cause of acute gastroenteritis in children worldwide. The most common VP7 genotype of human RVA is G1, but G1 is rarely detected in porcine strains. To understand the evolutionary relationships between human and porcine G1 VP7 genes, we sequenced the VP7 genes of three Japanese G1 porcine strains; the first two (PRV2, S80B) were isolated in 1980 and the third (Kyusyu-14) was isolated in 2001. Then, we performed phylogenetic and in-silico structural analyses. All three VP7 sequences clustered into lineage VI, and the mean nucleotide sequence identity between any pair of porcine G1 VP7 sequences belonging to lineage VI was 91.9%. In contrast, the mean nucleotide sequence identity between any pair of human G1 VP7 sequences belonging to lineages I-V was 95.5%. While the mean nucleotide sequence identity between any pair of porcine lineage VI strain and human lineage I-V strain was 85.4%, the VP7 genes of PRV2 and a rare porcine-like human G1P[6] strain (AU19) were 98% identical, strengthening the porcine RVA origin of AU19. The phylogenetic tree suggests that human G1 VP7 genes originated from porcine G1 VP7 genes. The time of their most recent common ancestor was estimated to be 1948, and human and porcine RVA strains evolved along independent pathways. In-silico structural analyses identified 7 amino acid residues within the known neutralisation epitopes that show differences in electric charges and shape between different porcine and human G1 strains. When compared with much divergent porcine G1 VP7 lineages, monophyletic, less divergent human G1 VP7 lineages support the hypothesis that all human G1 VP7 genes included in this study originated from a rare event of a porcine RVA transmitting to humans that was followed by successful adaptation to the human host. By contrast, AU19 represents interspecies transmission that terminated in dead-end infection. PMID:26961591

  13. Late Pleistocene human skull from Hofmeyr, South Africa, and modern human origins.

    PubMed

    Grine, F E; Bailey, R M; Harvati, K; Nathan, R P; Morris, A G; Henderson, G M; Ribot, I; Pike, A W G

    2007-01-12

    The lack of Late Pleistocene human fossils from sub-Saharan Africa has limited paleontological testing of competing models of recent human evolution. We have dated a skull from Hofmeyr, South Africa, to 36.2 +/- 3.3 thousand years ago through a combination of optically stimulated luminescence and uranium-series dating methods. The skull is morphologically modern overall but displays some archaic features. Its strongest morphometric affinities are with Upper Paleolithic (UP) Eurasians rather than recent, geographically proximate people. The Hofmeyr cranium is consistent with the hypothesis that UP Eurasians descended from a population that emigrated from sub-Saharan Africa in the Late Pleistocene. PMID:17218524

  14. The evolutionary origins of obstructed labor: bipedalism, encephalization, and the human obstetric dilemma.

    PubMed

    Wittman, Anna Blackburn; Wall, L Lewis

    2007-11-01

    Obstructed labor is a common complication of human childbirth. In parts of the world where access to emergency obstetric services is limited, obstructed labor is a major cause of maternal mortality. Women who survive the ordeal of prolonged obstructed labor often end up suffering from an obstetric vesicovaginal fistula or another serious birth injury that leaves them crippled for life. Compared with the other higher primates (chimpanzees, bonobos, gorillas, and orangutans), these problems are uniquely human. This article reviews the evolutionary origins of the human obstetric dilemma with special reference to the changes imposed on pelvic architecture by the assumption of upright, bipedal posture and locomotion. The subsequent development of progressively increasing brain size (encephalization) in hominins led to the present human obstetrical conundrum: how to balance the evolutionary advantage of bigger babies with larger brains against the presence of a narrow pelvis that is difficult for a fetus to traverse during labor. PMID:17925047

  15. The origin of representational drawing: a comparison of human children and chimpanzees.

    PubMed

    Saito, Aya; Hayashi, Misato; Takeshita, Hideko; Matsuzawa, Tetsuro

    2014-01-01

    To examine the evolutional origin of representational drawing, two experiments directly compared the drawing behavior of human children and chimpanzees. The first experiment observed free drawing after model presentation, using imitation task. From longitudinal observation of humans (N = 32, 11-31 months), the developmental process of drawing until the emergence of shape imitation was clarified. Adult chimpanzees showed the ability to trace a model, which was difficult for humans who had just started imitation. The second experiment, free drawing on incomplete facial stimuli, revealed the remarkable difference between two species. Humans (N = 57, 6-38 months) tend to complete the missing parts even with immature motor control, whereas chimpanzees never completed the missing parts and instead marked the existing parts or traced the outlines. Cognitive characteristics may affect the emergence of representational drawings. PMID:25376268

  16. Accelerated protein evolution and origins of human-specific features: Foxp2 as an example.

    PubMed Central

    Zhang, Jianzhi; Webb, David M; Podlaha, Ondrej

    2002-01-01

    Genes responsible for human-specific phenotypes may have been under altered selective pressures in human evolution and thus exhibit changes in substitution rate and pattern at the protein sequence level. Using comparative analysis of human, chimpanzee, and mouse protein sequences, we identified two genes (PRM2 and FOXP2) with significantly enhanced evolutionary rates in the hominid lineage. PRM2 is a histone-like protein essential to spermatogenesis and was previously reported to be a likely target of sexual selection in humans and chimpanzees. FOXP2 is a transcription factor involved in speech and language development. Human FOXP2 experienced a >60-fold increase in substitution rate and incorporated two fixed amino acid changes in a broadly defined transcription suppression domain. A survey of a diverse group of placental mammals reveals the uniqueness of the human FOXP2 sequence and a population genetic analysis indicates possible adaptive selection behind the accelerated evolution. Taken together, our results suggest an important role that FOXP2 may have played in the origin of human speech and demonstrate a strategy for identifying candidate genes underlying the emergences of human-specific features. PMID:12524352

  17. SIV infection of rhesus macaques of Chinese origin: a suitable model for HIV infection in humans.

    PubMed

    Zhou, Yu; Bao, Rong; Haigwood, Nancy L; Persidsky, Yuri; Ho, Wen-zhe

    2013-01-01

    Simian immunodeficiency virus (SIV) infection of Indian-origin rhesus macaques (RM) has been widely used as a well-established nonhuman primate (NHP) model for HIV/AIDS research. However, there have been a growing number of studies using Chinese RM to evaluate immunopathogenesis of SIV infection. In this paper, we have for the first time reviewed and discussed the major publications related to SIV or SHIV infection of Chinese RM in the past decades. We have compared the differences in the pathogenesis of SIV infection between Chinese RM and Indian RM with regard to viral infection, immunological response, and host genetic background. Given AIDS is a disease that affects humans of diverse origins, it is of importance to study animals with different geographical background. Therefore, to examine and compare results obtained from RM models of Indian and Chinese origins should lead to further validation and improvement of these animal models for HIV/AIDS research. PMID:23947613

  18. [Human infection due to Bertiella sp (cestode: Anoplocephalidae) in a man originating from Yemen in Algeria].

    PubMed

    Achir, I; Zaït, H; Hamrioui, B

    2008-04-01

    Bertiella is a frequent parasite in animals, particularly in nonhuman primates. The infestation occurs in man by accidental ingestion of the intermediate host, an acarus containing the cysticercoid larva of Bertiella studeri or Bertiella mucronata. The diagnosis is based on the morphology of the gravid proglottis and eggs with pyriform embryo which is characteristic of the Anoplocephalinae. Human infection is asymptomatic or can induce minor non specific digestive disturbances and the niclosamide is effective in one single dose. The authors report the first case of human bertiellosis in Algeria in a student originating from Yemen. PMID:18543702

  19. Models and realities in modern human origins: the African fossil evidence.

    PubMed

    Smith, F H

    1992-08-29

    The recent application of such chronometric techniques as electron spin resonance (ESR), thermoluminescence (TL), and uranium series dating has had a significant impact on perceptions of modern human origins. Claims for the presence of anatomically modern humans in Africa prior to 100 ka and for the transition leading to modern Africans at an even earlier date have been made, partly based on results of these techniques. However, a careful examination of the pertinent record shows that these claims are not unequivocally supported by the available fossil and chronological evidence. PMID:1357699

  20. Emergence of Antimicrobial-Resistant Escherichia coli of Animal Origin Spreading in Humans.

    PubMed

    Skurnik, David; Clermont, Olivier; Guillard, Thomas; Launay, Adrien; Danilchanka, Olga; Pons, Stéphanie; Diancourt, Laure; Lebreton, François; Kadlec, Kristina; Roux, Damien; Jiang, Deming; Dion, Sara; Aschard, Hugues; Denamur, Maurice; Cywes-Bentley, Colette; Schwarz, Stefan; Tenaillon, Olivier; Andremont, Antoine; Picard, Bertrand; Mekalanos, John; Brisse, Sylvain; Denamur, Erick

    2016-04-01

    In the context of the great concern about the impact of human activities on the environment, we studied 403 commensal Escherichia coli/Escherichia clade strains isolated from several animal and human populations that have variable contacts to one another. Multilocus sequence typing (MLST) showed a decrease of diversity 1) in strains isolated from animals that had an increasing contact with humans and 2) in all strains that had increased antimicrobial resistance. A specific B1 phylogroup clonal complex (CC87, Institut Pasteur schema nomenclature) of animal origin was identified and characterized as being responsible for the increased antimicrobial resistance prevalence observed in strains from the environments with a high human-mediated antimicrobial pressure. CC87 strains have a high capacity of acquiring and disseminating resistance genes with specific metabolic and genetic determinants as demonstrated by high-throughput sequencing and phenotyping. They are good mouse gut colonizers but are not virulent. Our data confirm the predominant role of human activities in the emergence of antimicrobial resistance in the environmental bacterial strains and unveil a particular E. coli clonal complex of animal origin capable of spreading antimicrobial resistance to other members of microbial communities. PMID:26613786

  1. Phylogenetic Origin of Human Chromosomes 7, 16, and 19 and their Homologs in Placental Mammals

    PubMed Central

    Richard, Florence; Lombard, Martine; Dutrillaux, Bernard

    2000-01-01

    The origin of human chromosomes (HSA) 7, 16, and 19 was studied by comparing data obtained from chromosome banding, chromosome painting, and gene mapping in species belonging to 11 orders of placental mammals (Eutherians). This allowed us to propose the reconstruction of their presumed ancestral forms. The HSA7 homologs were composed of two parts, the largest forming an acrocentric. The smallest formed one arm of a small submetacentric; the other arm was composed of sequences homologous to the short arm of HSA16 (HSA16p). The sequences homologous to the long arm of HSA16 (HSA16q) were associated with sequences homologous to the long arm of HSA19 (HSA19q) and formed another submetacentric. From their origin, these chromosomes underwent the following rearrangements to give rise to current human chromosomes: centromeric fission of the two submetacentrics in ancestors of all primates (∼80 million years ago); fusion of the HSA19p and HSA19q sequences, originating the current HSA19, in ancestors of all simians (∼55 million years ago); fusions of the HSA16p and HSA16q sequences, originating the current HSA16 and the two components of HSA7 before the separation of Cercopithecoids and Hominoids (∼35 million years ago); and finally, pericentric and paracentric inversions of the homologs to HSA7 after the divergence of orangutan and gorilla, respectively. Thus, compared with HSA16 and HSA19, HSA7 is a fairly recent chromosome shared by man and chimpanzee only. PMID:10810086

  2. Histological determination of the human origin from dry bone: a cautionary note for subadults.

    PubMed

    Caccia, Giulia; Magli, Francesca; Tagi, Veronica Maria; Porta, Davide Guido Ampelio; Cummaudo, Marco; Márquez-Grant, Nicholas; Cattaneo, Cristina

    2016-01-01

    Anthropologists are frequently required to confirm or exclude the human origin of skeletal remains; DNA and protein radioimmunoassays are useful in confirming the human origin of bone fragments but are not always successful. Histology may be the solution, but the young subadult structure could create misinterpretation. Histological tests were conducted on femur and skull of 31 human subjects. Each sample was observed focusing on presence or absence of fibrous bone, lamellar bone, radial lamellar bone, plexiform bone, reticular pattern, osteon banding, Haversian bone, primary osteons, secondary osteon and osteon fragments. Samples were divided into five age classes; 1 (<1 year), 2 (1-5 years), 3 (6-10 years), 4 (11-15 years) and 5 (16-20 years). Regarding femurs, class 1 presented the following: 87.5% fibrous bone, 37.5% plexiform bone, 12.5% reticular pattern and 12.5% lamellar bone radially oriented. Class 2 showed 37.5% of fibrous bone, 12.5% of reticular pattern and 37.5% of osteon banding. In the higher age classes, the classical human structures, lamellar bone and osteons were frequently visible, except for one case of reticular pattern, generally considered a distinctive non-human structure. The situation appeared different for the skull, where there was a lack of similar information, both in human and non-human. An analysis of the percentage of lamellar bone and osteons was conducted on femur and skull fragments. A trend of increase of primary osteon number and a decrease of the lamellar bone area has been detected in the femur. The present study has therefore shed some light on further pitfalls in species determination of subadult bone. PMID:26563342

  3. The origin of intermittent exhalation (A! Ha! Ha!) peculiar to human laugh.

    PubMed

    Sumitsuji, N

    2000-01-01

    Since Darwin (1872), the origin of the laugh with an intermittent exhalation "A! Ha! Ha!" which is peculiar to human, has been a great question. The author found out that this laugh is caused by the three sets of emotion. Firstly, light surprise or discovery. The ability to estimate "light" is absolutely important, because the amount of the first exhalation "A!" caused by the stimulation is decided by the amount of "surprise" felt by the subject. The ability to estimate the amount of "surprise" to be "light", makes the partial exhalation "A!". Secondly, consciousness of this harmlessness or delight, and thirdly, the following expectation of some safe circumstances. The author proved this theory by electromyography (EMG), photoplethysmography and galvanic skin reaction (GSR). The similarity between the facial EMG distribution pattern of "the beginning of laugh" and "the light surprise" was proved by electromyography about many facial muscles, with special fine electrode which did not disturb any natural facial expression of the subjects. Plethysmography and GSR proved light sympathetic tension and following relaxation when laughing. The author also suggests relationships between human laugh and human history such as the origin of clothing, language, and use of fire, which are specific in human. PMID:10938997

  4. The Renaissance. Grade 7 Model Lesson for Standard 7.8. World History and Geography: Medieval and Early Modern Times. California History-Social Science Course Models.

    ERIC Educational Resources Information Center

    Zachlod, Michelle, Ed.

    California State Standard 7.8 is delineated in the following manner: "Students analyze the origins, accomplishments, and diffusion of the Renaissance," in terms of the way in which the revival of classical learning and the arts affected a new interest in humanism; the importance of Florence in the early stages of the Renaissance and the growth of…

  5. The Renaissance. Grade 7 Model Lesson for Standard 7.8. World History and Geography: Medieval and Early Modern Times. California History-Social Science Course Models.

    ERIC Educational Resources Information Center

    Zachlod, Michelle, Ed.

    California State Standard 7.8 is delineated in the following manner: "Students analyze the origins, accomplishments, and diffusion of the Renaissance," in terms of the way in which the revival of classical learning and the arts affected a new interest in humanism; the importance of Florence in the early stages of the Renaissance and the growth of

  6. Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin

    PubMed Central

    Dorn, Isabel; Klich, Katharina; Arauzo-Bravo, Marcos J.; Radstaak, Martina; Santourlidis, Simeon; Ghanjati, Foued; Radke, Teja F.; Psathaki, Olympia E.; Hargus, Gunnar; Kramer, Jan; Einhaus, Martin; Kim, Jeong Beom; Kögler, Gesine; Wernet, Peter; Schöler, Hans R.; Schlenke, Peter; Zaehres, Holm

    2015-01-01

    Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34+ hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34+ hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34+ hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34+ cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential. PMID:25326431

  7. The human genome retains relics of its prokaryotic ancestry: human genes of archaebacterial and eubacterial origin exhibit remarkable differences.

    PubMed

    Alvarez-Ponce, David; McInerney, James O

    2011-01-01

    Eukaryotes are generally thought to stem from a fusion event involving an archaebacterium and a eubacterium. As a result of this event, contemporaneous eukaryotic genomes are chimeras of genes inherited from both endosymbiotic partners. These two coexisting gene repertoires have been shown to differ in a number of ways in yeast. Here we combine genomic and functional data in order to determine if and how human genes that have been inherited from both prokaryotic ancestors remain distinguishable. We show that, despite being fewer in number, human genes of archaebacterial origin are more highly and broadly expressed across tissues, are more likely to have lethal mouse orthologs, tend to be involved in informational processes, are more selectively constrained, and encode shorter and more central proteins in the protein-protein interaction network than eubacterium-like genes. Furthermore, consistent with endosymbiotic theory, we show that proteins tend to interact with those encoded by genes of the same ancestry. Most interestingly from a human health perspective, archaebacterial genes are less likely to be involved in heritable human disease. Taken together, these results show that more than 2 billion years after eukaryogenesis, the human genome retains at least two somewhat distinct communities of genes. PMID:21795752

  8. Characterization of Temperate Phages Infecting Clostridium difficile Isolates of Human and Animal Origins

    PubMed Central

    Sekulovic, Ognjen; Garneau, Julian R.; Néron, Audrey

    2014-01-01

    Clostridium difficile is a Gram-positive pathogen infecting humans and animals. Recent studies suggest that animals could represent potential reservoirs of C. difficile that could then transfer to humans. Temperate phages contribute to the evolution of most bacteria, for example, by promoting the transduction of virulence, fitness, and antibiotic resistance genes. In C. difficile, little is known about their role, mainly because suitable propagating hosts and conditions are lacking. Here we report the isolation, propagation, and preliminary characterization of nine temperate phages from animal and human C. difficile isolates. Prophages were induced by UV light from 58 C. difficile isolates of animal and human origins. Using soft agar overlays with 27 different C. difficile test strains, we isolated and further propagated nine temperate phages: two from horse isolates (ϕCD481-1 and ϕCD481-2), three from dog isolates (ϕCD505, ϕCD506, and ϕCD508), and four from human isolates (ϕCD24-2, ϕCD111, ϕCD146, and ϕCD526). Two phages are members of the Siphoviridae family (ϕCD111 and ϕCD146), while the others are Myoviridae phages. Pulsed-field gel electrophoresis and restriction enzyme analyses showed that all of the phages had unique double-stranded DNA genomes of 30 to 60 kb. Phages induced from human C. difficile isolates, especially the members of the Siphoviridae family, had a broader host range than phages from animal C. difficile isolates. Nevertheless, most of the phages could infect both human and animal strains. Phage transduction of antibiotic resistance was recently reported in C. difficile. Our findings therefore call for further investigation of the potential risk of transduction between animal and human C. difficile isolates. PMID:24532062

  9. Characterization of temperate phages infecting Clostridium difficile isolates of human and animal origins.

    PubMed

    Sekulovic, Ognjen; Garneau, Julian R; Néron, Audrey; Fortier, Louis-Charles

    2014-04-01

    Clostridium difficile is a Gram-positive pathogen infecting humans and animals. Recent studies suggest that animals could represent potential reservoirs of C. difficile that could then transfer to humans. Temperate phages contribute to the evolution of most bacteria, for example, by promoting the transduction of virulence, fitness, and antibiotic resistance genes. In C. difficile, little is known about their role, mainly because suitable propagating hosts and conditions are lacking. Here we report the isolation, propagation, and preliminary characterization of nine temperate phages from animal and human C. difficile isolates. Prophages were induced by UV light from 58 C. difficile isolates of animal and human origins. Using soft agar overlays with 27 different C. difficile test strains, we isolated and further propagated nine temperate phages: two from horse isolates (ΦCD481-1 and ΦCD481-2), three from dog isolates (ΦCD505, ΦCD506, and ΦCD508), and four from human isolates (ΦCD24-2, ΦCD111, ΦCD146, and ΦCD526). Two phages are members of the Siphoviridae family (ΦCD111 and ΦCD146), while the others are Myoviridae phages. Pulsed-field gel electrophoresis and restriction enzyme analyses showed that all of the phages had unique double-stranded DNA genomes of 30 to 60 kb. Phages induced from human C. difficile isolates, especially the members of the Siphoviridae family, had a broader host range than phages from animal C. difficile isolates. Nevertheless, most of the phages could infect both human and animal strains. Phage transduction of antibiotic resistance was recently reported in C. difficile. Our findings therefore call for further investigation of the potential risk of transduction between animal and human C. difficile isolates. PMID:24532062

  10. Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception.

    PubMed

    Kang, Kyeongjin; Pulver, Stefan R; Panzano, Vincent C; Chang, Elaine C; Griffith, Leslie C; Theobald, Douglas L; Garrity, Paul A

    2010-03-25

    Chemical nociception, the detection of tissue-damaging chemicals, is important for animal survival and causes human pain and inflammation, but its evolutionary origins are largely unknown. Reactive electrophiles are a class of noxious compounds humans find pungent and irritating, such as allyl isothiocyanate (in wasabi) and acrolein (in cigarette smoke). Diverse animals, from insects to humans, find reactive electrophiles aversive, but whether this reflects conservation of an ancient sensory modality has been unclear. Here we identify the molecular basis of reactive electrophile detection in flies. We demonstrate that Drosophila TRPA1 (Transient receptor potential A1), the Drosophila melanogaster orthologue of the human irritant sensor, acts in gustatory chemosensors to inhibit reactive electrophile ingestion. We show that fly and mosquito TRPA1 orthologues are molecular sensors of electrophiles, using a mechanism conserved with vertebrate TRPA1s. Phylogenetic analyses indicate that invertebrate and vertebrate TRPA1s share a common ancestor that possessed critical characteristics required for electrophile detection. These findings support emergence of TRPA1-based electrophile detection in a common bilaterian ancestor, with widespread conservation throughout vertebrate and invertebrate evolution. Such conservation contrasts with the evolutionary divergence of canonical olfactory and gustatory receptors and may relate to electrophile toxicity. We propose that human pain perception relies on an ancient chemical sensor conserved across approximately 500 million years of animal evolution. PMID:20237474

  11. Prevalence of a human retrovirus in native Japanese: evidence for a possible ancient origin.

    PubMed

    Ishida, T; Yamamoto, K; Omoto, K; Iwanaga, M; Osato, T; Hinuma, Y

    1985-09-01

    The origin of a human retrovirus (ATLV or HTLV-I) is, at present, unknown although carriers of the virus have been found in Japan, the Caribbean basin and Africa. By means of a sero-epidemiological study, the Ainu people of Hokkaido, located in the northernmost island of Japan, were shown to have antibody to the virus in high frequency. Since the Ainu are regarded as descendants of the pre-agriculture native population of northern Japan, this finding appears to indicate that the retrovirus was already present in the aboriginal Japanese of prehistoric times. PMID:2997332

  12. Virulence properties of Campylobacter jejuni isolates of poultry and human origin.

    PubMed

    Van Deun, Kim; Haesebrouck, Freddy; Heyndrickx, Marc; Favoreel, Herman; Dewulf, Jeroen; Ceelen, Liesbeth; Dumez, Linn; Messens, Winy; Leleu, Saskia; Van Immerseel, Filip; Ducatelle, Richard; Pasmans, Frank

    2007-10-01

    Campylobacter jejuni is one of the leading causes of food-borne gastroenteritis. Because of the high prevalence of C. jejuni in poultry, poultry meat is considered a major source of C. jejuni infections for humans. However, it is not known whether all poultry-associated C. jejuni strains are capable of causing disease in humans. Four different virulence properties of C. jejuni strains were compared between 20 poultry isolates and 24 human isolates. Strains were chosen based on their PFGE pattern to represent a heterogeneous population. The isolates were compared for their ability to invade and induce interleukin-8 (IL-8) production in T84 cells, their production of functional cytolethal distending toxin (CDT) using HEp-2 cells, and their sodium deoxycholate resistance. All four virulence factors were present among strains of human and poultry origin, with strong differences observed among strains. For invasion and IL-8 induction, no difference was observed between the two populations. However, on average, human isolates arrested more HEp-2 cells in their cell cycle than did the poultry isolates (P=0.041), suggesting higher CDT production by the former. The ability to survive 16 000 mug sodium deoxycholate ml(-1) was significantly more pronounced (P=0.006) among human isolates than poultry isolates, although all strains possessed the cmeABC operon. These data suggest that all four virulence properties are widespread among C. jejuni isolates, but that a higher degree of bile-salt resistance and more pronounced CDT production are associated with strains causing enteritis in humans. PMID:17893162

  13. Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos.

    PubMed

    McCoy, Rajiv C; Demko, Zachary; Ryan, Allison; Banjevic, Milena; Hill, Matthew; Sigurjonsson, Styrmir; Rabinowitz, Matthew; Fraser, Hunter B; Petrov, Dmitri A

    2015-04-10

    Aneuploidy, the inheritance of an atypical chromosome complement, is common in early human development and is the primary cause of pregnancy loss. By screening day-3 embryos during in vitro fertilization cycles, we identified an association between aneuploidy of putative mitotic origin and linked genetic variants on chromosome 4 of maternal genomes. This associated region contains a candidate gene, Polo-like kinase 4 (PLK4), that plays a well-characterized role in centriole duplication and has the ability to alter mitotic fidelity upon minor dysregulation. Mothers with the high-risk genotypes contributed fewer embryos for testing at day 5, suggesting that their embryos are less likely to survive to blastocyst formation. The associated region coincides with a signature of a selective sweep in ancient humans, suggesting that the causal variant was either the target of selection or hitchhiked to substantial frequency. PMID:25859044

  14. Uptake, accumulation, and egress of erythromycin by tissue culture cells of human origin.

    PubMed Central

    Martin, J R; Johnson, P; Miller, M F

    1985-01-01

    The ability of erythromycin A base to penetrate and accumulate in tissue culture cells of human origin was investigated. The antibiotic was highly concentrated by early passage cells of normal bronchus, kidney, liver, lung, and skin and by cancer cells derived from breast, liver, and lung. Intracellular levels 4 to 12 times that of the extracellular milieu were obtained in both early-passage and transformed cells. The total quantity of erythromycin accumulated depended on the extracellular concentration of antibiotic, but the cellular/extracellular ratios were, for the most part, independent of the initial extracellular drug concentration. In all cell types tested, the accumulated antibiotic rapidly egressed when cells were incubated in antibiotic-free medium. Bioactivity assays demonstrated that the expelled drug was unmetabolized, fully active antibiotic. The concentration of erythromycin by a variety of human cell types probably accounts, in part, for the effectiveness of the antibiotic against intracellular parasites such as Legionella and Chlamydia spp. PMID:3994346

  15. [Healing Dental and Oral Problems by Remedies of Animal and of Human Origin].

    PubMed

    Kaán, Miklós

    2015-01-01

    Use of matierials of animal or human origin in dentistry (and generally in medicine) these days is regarded as an unusal way of intervention. However in earlier times, different tissues, parts, products and organs of animals were frequently used in healing. Some of these methods were rooted in magical thinking. As analogical treatments--based on similarity or analogy--e.g. powder of horn or teeth of pike was used for the treatment of decayed teeth and different worms, maggots, veenies were applied against "toothworm". By difficult eruption of primary teeth bone marrow or brain mixed with cockridge-blood and goatmilk was a widely used medicine. Butter and honey were able to help the growing of teeth, as well. Parts of frog (fe: flippers) were also components of curing materials. Egg as the symbol of life was often an ingredient of medicaments. For the treatment of inflamed gum different animal materials were used, like chin and teeth of wolf, pike, crayfish, milk, honey, human saliva etc. Animal or human stools, mucks (containing enzymes) did one's bit in healing of oral and dental illnesses and were applied as fomentation or swathing. Placing a leech on the inflamed face was a common procedure in the past even as the use of earwax in lipnook. In our days tissues, parts or products of animals (or human beings) usually never allowed to get into contact with the body of patients. It's a much safer routine, at the same time however a precious traditional knowledge vanishes forever. PMID:26875294

  16. Automatic Extraction of Destinations, Origins and Route Parts from Human Generated Route Directions

    NASA Astrophysics Data System (ADS)

    Zhang, Xiao; Mitra, Prasenjit; Klippel, Alexander; Maceachren, Alan

    Researchers from the cognitive and spatial sciences are studying text descriptions of movement patterns in order to examine how humans communicate and understand spatial information. In particular, route directions offer a rich source of information on how cognitive systems conceptualize movement patterns by segmenting them into meaningful parts. Route directions are composed using a plethora of cognitive spatial organization principles: changing levels of granularity, hierarchical organization, incorporation of cognitively and perceptually salient elements, and so forth. Identifying such information in text documents automatically is crucial for enabling machine-understanding of human spatial language. The benefits are: a) creating opportunities for large-scale studies of human linguistic behavior; b) extracting and georeferencing salient entities (landmarks) that are used by human route direction providers; c) developing methods to translate route directions to sketches and maps; and d) enabling queries on large corpora of crawled/analyzed movement data. In this paper, we introduce our approach and implementations that bring us closer to the goal of automatically processing linguistic route directions. We report on research directed at one part of the larger problem, that is, extracting the three most critical parts of route directions and movement patterns in general: origin, destination, and route parts. We use machine-learning based algorithms to extract these parts of routes, including, for example, destination names and types. We prove the effectiveness of our approach in several experiments using hand-tagged corpora.

  17. Geographic population structure analysis of worldwide human populations infers their biogeographical origins.

    PubMed

    Elhaik, Eran; Tatarinova, Tatiana; Chebotarev, Dmitri; Piras, Ignazio S; Maria Calò, Carla; De Montis, Antonella; Atzori, Manuela; Marini, Monica; Tofanelli, Sergio; Francalacci, Paolo; Pagani, Luca; Tyler-Smith, Chris; Xue, Yali; Cucca, Francesco; Schurr, Theodore G; Gaieski, Jill B; Melendez, Carlalynne; Vilar, Miguel G; Owings, Amanda C; Gómez, Rocío; Fujita, Ricardo; Santos, Fabrício R; Comas, David; Balanovsky, Oleg; Balanovska, Elena; Zalloua, Pierre; Soodyall, Himla; Pitchappan, Ramasamy; Ganeshprasad, Arunkumar; Hammer, Michael; Matisoo-Smith, Lisa; Wells, R Spencer

    2014-01-01

    The search for a method that utilizes biological information to predict humans' place of origin has occupied scientists for millennia. Over the past four decades, scientists have employed genetic data in an effort to achieve this goal but with limited success. While biogeographical algorithms using next-generation sequencing data have achieved an accuracy of 700 km in Europe, they were inaccurate elsewhere. Here we describe the Geographic Population Structure (GPS) algorithm and demonstrate its accuracy with three data sets using 40,000-130,000 SNPs. GPS placed 83% of worldwide individuals in their country of origin. Applied to over 200 Sardinians villagers, GPS placed a quarter of them in their villages and most of the rest within 50 km of their villages. GPS's accuracy and power to infer the biogeography of worldwide individuals down to their country or, in some cases, village, of origin, underscores the promise of admixture-based methods for biogeography and has ramifications for genetic ancestry testing. PMID:24781250

  18. A view of modern human origins from Y chromosome microsatellite variation.

    PubMed

    Seielstad, M; Bekele, E; Ibrahim, M; Tour, A; Traor, M

    1999-06-01

    The idea that all modern humans share a recent (within the last 150, 000 years) African origin has been proposed and supported on the basis of three observations. Most genetic loci examined to date have (1) shown greater diversity in African populations than in others, (2) placed the first branch between African and all non-African populations in phylogenetic trees, and (3) indicated recent dates for either the molecular coalescence (with the exception of some autosomal and X-chromosomal loci) or for the time of separation between African and non-African populations. We analyze variation at 10 Y chromosome microsatellite loci that were typed in 506 males representing 49 populations and every inhabited continent and find significantly greater Y chromosome diversity in Africa than elsewhere, find the first branch in phylogenetic trees of the continental populations to fall between African and all non-African populations, and date this branching with the (deltamu)2 distance measure to 5800-17,400 or 12,800-36,800 years BP depending on the mutation rate used. The magnitude of the excess Y chromosome diversity in African populations appears to result from a greater antiquity of African populations rather than a greater long-term effective population size. These observations are most consistent with a recent African origin for all modern humans. PMID:10400923

  19. The Ribagorda sand gully (east-central Spain): Sediment yield and human-induced origin

    NASA Astrophysics Data System (ADS)

    Martín-Moreno, C.; Fidalgo Hijano, C.; Martín Duque, J. F.; González Martín, J. A.; Zapico Alonso, I.; Laronne, J. B.

    2014-11-01

    Gullies are developed under different climatic conditions and lithologies; however, those formed on sands have been scarcely described. This paper reports the study of the Ribagorda sand gully, 2.57 ha in area (east-central Spain). The main objectives were to characterize and quantify its geomorphic dynamics and to trace its origin. We described the landforms of the gully and measured the surface strength of the sand. We monitored, for six years, the filling of the storage areas of three check dams built downstream from the gully, and related it with rainfall characteristics. We also described the nature of the sediments trapped by the dams and estimated the amount of sediment eroded since the gully formation. Finally, we consulted historical records and maps to determine past land uses and transformations that may have affected the origin of the gully. The study shows a high diversity of landforms, denoting active processes, consistent with a measured mean annual sediment yield of 114 Mg ha- 1 yr- 1. A statistically significant relationship exists between the mass of sediment (Mg) and: 1) the total rainfall (mm) (P = 0.0007) or 2) the analysed rainfall intensities. Among five identified facies in the sedimentary wedge, the sandy ones are predominant. The total amount of sediment eroded by the Ribagorda gully since its origin was 962,800 Mg. The results are unequivocal signs of an intense geomorphic activity within the gully, with an alluvial-fan type deposition in the dams. We interpret that the Ribagorda gully was initiated by deforestation after the 13th century, when forests began to be intensively logged, and before the 18th century, when the gully was first indirectly described in print. The age, origin, evolution and dynamics of this gully indicate that this landscape is currently evolving towards a new steady state, after human disturbances over centuries. Given the gully evolution and local extent, we suggest that no correction measures are needed for its management.

  20. Open chromatin encoded in DNA sequence is the signature of ‘master’ replication origins in human cells

    PubMed Central

    Audit, Benjamin; Zaghloul, Lamia; Vaillant, Cédric; Chevereau, Guillaume; d'Aubenton-Carafa, Yves; Thermes, Claude; Arneodo, Alain

    2009-01-01

    For years, progress in elucidating the mechanisms underlying replication initiation and its coupling to transcriptional activities and to local chromatin structure has been hampered by the small number (approximately 30) of well-established origins in the human genome and more generally in mammalian genomes. Recent in silico studies of compositional strand asymmetries revealed a high level of organization of human genes around 1000 putative replication origins. Here, by comparing with recently experimentally identified replication origins, we provide further support that these putative origins are active in vivo. We show that regions ∼300-kb wide surrounding most of these putative replication origins that replicate early in the S phase are hypersensitive to DNase I cleavage, hypomethylated and present a significant enrichment in genomic energy barriers that impair nucleosome formation (nucleosome-free regions). This suggests that these putative replication origins are specified by an open chromatin structure favored by the DNA sequence. We discuss how this distinctive attribute makes these origins, further qualified as ‘master’ replication origins, priviledged loci for future research to decipher the human spatio-temporal replication program. Finally, we argue that these ‘master’ origins are likely to play a key role in genome dynamics during evolution and in pathological situations. PMID:19671527

  1. Competence and the Evolutionary Origins of Status and Power in Humans.

    PubMed

    Chapais, Bernard

    2015-06-01

    In this paper I propose an evolutionary model of human status that expands upon an earlier model proposed by Henrich and Gil-White Evolution and Human Behavior, 22,165-196 (2001). According to their model, there are two systems of status attainment in humans-"two ways to the top": the dominance route, which involves physical intimidation, a psychology of fear and hubristic pride, and provides coercive power, and the prestige route, which involves skills and knowledge (competence), a psychology of attraction to experts and authentic pride, and translates mainly into influence. The two systems would have evolved in response to different selective pressures, with attraction to experts serving a social learning function and coinciding with the evolution of cumulative culture. In this paper I argue that (1) the only one way to the top is competence because dominance itself involves competence and confers prestige, so there is no such thing as pure dominance status; (2) dominance in primates has two components: a competitive one involving physical coercion and a cooperative one involving competence-based attraction to high-ranking individuals (proto-prestige); (3) competence grants the same general type of power (dependence-based) in humans and other primates; (4) the attractiveness of high rank in primates is homologous with the admiration of experts in humans; (5) upon the evolution of cumulative culture, the attractiveness of high rank was co-opted to generate status differentials in a vast number of culturally generated domains of activity. I also discuss, in this perspective, the origins of hubristic pride, authentic pride, and nonauthoritarian leadership. PMID:25947621

  2. [The unicorn and the pharmacists. Early modern views on the presumed anti-toxic effects of unicorn horn].

    PubMed

    Gerritsen, W P

    2007-01-01

    Around 1600, the age-old belief in the anti-toxic effect of unicorn horn began to be called into question. This is evidenced by the views of two well-known French pharmaceutic authorities whose publications are discussed in this paper: the surgeon Ambroise Paré (1510-1590), court physician to four French kings, and the Montpellier pharmacist Laurent Catelan (1568-1647), who owned a famous cabinet de curiosités. Although Paré had to accept, however reluctantly, the existence of the unicorn (since it is mentioned in the Bible), he vehemently denied the supposed medicinal effect of unicorn products. He defended his position by an appeal to ancient and contemporary authorities, by rational argumentation, and by experiment. Paré's arguments failed to convince Catelan, who adhered to an alternative, so-called spagyric, medical theory of neoplatonic inspiration, as propagated by Paracelsus and Ficino. Catelan remained convinced of the efficacity of unicorn horn, which in his view could drain the human body from any poisonous substance. The medical establishment being reluctant to give up a rewarding source of income,'unicorn' remained much in demand as a prescription. PMID:20681192

  3. Spatial dynamics of human-origin H1 influenza A virus in North American swine.

    PubMed

    Nelson, Martha I; Lemey, Philippe; Tan, Yi; Vincent, Amy; Lam, Tommy Tsan-Yuk; Detmer, Susan; Viboud, Cécile; Suchard, Marc A; Rambaut, Andrew; Holmes, Edward C; Gramer, Marie

    2011-06-01

    The emergence and rapid global spread of the swine-origin H1N1/09 pandemic influenza A virus in humans underscores the importance of swine populations as reservoirs for genetically diverse influenza viruses with the potential to infect humans. However, despite their significance for animal and human health, relatively little is known about the phylogeography of swine influenza viruses in the United States. This study utilizes an expansive data set of hemagglutinin (HA1) sequences (n = 1516) from swine influenza viruses collected in North America during the period 2003-2010. With these data we investigate the spatial dissemination of a novel influenza virus of the H1 subtype that was introduced into the North American swine population via two separate human-to-swine transmission events around 2003. Bayesian phylogeographic analysis reveals that the spatial dissemination of this influenza virus in the US swine population follows long-distance swine movements from the Southern US to the Midwest, a corn-rich commercial center that imports millions of swine annually. Hence, multiple genetically diverse influenza viruses are introduced and co-circulate in the Midwest, providing the opportunity for genomic reassortment. Overall, the Midwest serves primarily as an ecological sink for swine influenza in the US, with sources of virus genetic diversity instead located in the Southeast (mainly North Carolina) and South-central (mainly Oklahoma) regions. Understanding the importance of long-distance pig transportation in the evolution and spatial dissemination of the influenza virus in swine may inform future strategies for the surveillance and control of influenza, and perhaps other swine pathogens. PMID:21695237

  4. Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells.

    PubMed

    Kliszczak, Maciej; Sedlackova, Hana; Pitchai, Ganesha P; Streicher, Werner W; Krejci, Lumir; Hickson, Ian D

    2015-12-01

    DNA replication is a highly coordinated process that is initiated at multiple replication origins in eukaryotes. These origins are bound by the origin recognition complex (ORC), which subsequently recruits the Mcm2-7 replicative helicase in a Cdt1/Cdc6-dependent manner. In budding yeast, two essential replication factors, Sld2 and Mcm10, are then important for the activation of replication origins. In humans, the putative Sld2 homolog, RECQ4, interacts with MCM10. Here, we have identified two mutants of human RECQ4 that are deficient in binding to MCM10. We show that these RECQ4 variants are able to complement the lethality of an avian cell RECQ4 deletion mutant, indicating that the essential function of RECQ4 in vertebrates is unlikely to require binding to MCM10. Nevertheless, we show that the RECQ4-MCM10 interaction is important for efficient replication origin firing. PMID:26588054

  5. Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells

    PubMed Central

    Kliszczak, Maciej; Sedlackova, Hana; Pitchai, Ganesha P.; Streicher, Werner W.; Krejci, Lumir; Hickson, Ian D.

    2015-01-01

    DNA replication is a highly coordinated process that is initiated at multiple replication origins in eukaryotes. These origins are bound by the origin recognition complex (ORC), which subsequently recruits the Mcm2-7 replicative helicase in a Cdt1/Cdc6-dependent manner. In budding yeast, two essential replication factors, Sld2 and Mcm10, are then important for the activation of replication origins. In humans, the putative Sld2 homolog, RECQ4, interacts with MCM10. Here, we have identified two mutants of human RECQ4 that are deficient in binding to MCM10. We show that these RECQ4 variants are able to complement the lethality of an avian cell RECQ4 deletion mutant, indicating that the essential function of RECQ4 in vertebrates is unlikely to require binding to MCM10. Nevertheless, we show that the RECQ4-MCM10 interaction is important for efficient replication origin firing. PMID:26588054

  6. Upper Pleistocene Human Dispersals out of Africa: A Review of the Current State of the Debate

    PubMed Central

    Beyin, Amanuel

    2011-01-01

    Although there is a general consensus on African origin of early modern humans, there is disagreement about how and when they dispersed to Eurasia. This paper reviews genetic and Middle Stone Age/Middle Paleolithic archaeological literature from northeast Africa, Arabia, and the Levant to assess the timing and geographic backgrounds of Upper Pleistocene human colonization of Eurasia. At the center of the discussion lies the question of whether eastern Africa alone was the source of Upper Pleistocene human dispersals into Eurasia or were there other loci of human expansions outside of Africa? The reviewed literature hints at two modes of early modern human colonization of Eurasia in the Upper Pleistocene: (i) from multiple Homo sapiens source populations that had entered Arabia, South Asia, and the Levant prior to and soon after the onset of the Last Interglacial (MIS-5), (ii) from a rapid dispersal out of East Africa via the Southern Route (across the Red Sea basin), dating to ~74–60 kya. PMID:21716744

  7. The origin and dispersion of human parasitic diseases in the old world (Africa, Europe and Madagascar).

    PubMed

    Nozais, Jean-Pierre

    2003-01-01

    The ancestors of present-day man (Homo sapiens sapiens) appeared in East Africa some three and a half million years ago (Australopithecs), and then migrated to Europe, Asia, and later to the Americas, thus beginning the differentiation process. The passage from nomadic to sedentary life took place in the Middle East in around 8000 BC. Wars, spontaneous migrations and forced migrations (slave trade) led to enormous mixtures of populations in Europe and Africa and favoured the spread of numerous parasitic diseases with specific strains according to geographic area. The three human plasmodia (Plasmodium falciparum, P. vivax, and P. malariae) were imported from Africa into the Mediterranean region with the first human migrations, but it was the Neolithic revolution (sedentarisation, irrigation, population increase) which brought about actual foci for malaria. The reservoir for Leishmania infantum and L. donovani--the dog--has been domesticated for thousands of years. Wild rodents as reservoirs of L. major have also long been in contact with man and probably were imported from tropical Africa across the Sahara. L. tropica, by contrast, followed the migrations of man, its only reservoir. L. infantum and L. donovani spread with man and his dogs from West Africa. Likewise, for thousands of years, the dog has played an important role in the spread and the endemic character of hydatidosis through sheep (in Europe and North Africa) and dromadary (in the Sahara and North Africa). Schistosoma haematobium and S. mansoni have existed since prehistoric times in populations living in or passing through the Sahara. These populations then transported them to countries of Northern Africa where the specific, intermediary hosts were already present. Madagascar was inhabited by populations of Indonesian origin who imported lymphatic filariosis across the Indian Ocean (possibly of African origin since the Indonesian sailors had spent time on the African coast before reaching Madagascar). Migrants coming from Africa and Arabia brought with them the two African forms of bilharziosis: S. haematobium and S. mansoni. PMID:12687757

  8. Parental origin effects in human trisomy for chromosome 14q: implications for genomic imprinting.

    PubMed Central

    Georgiades, P; Chierakul, C; Ferguson-Smith, A C

    1998-01-01

    Parental origin specific congenital anomalies have been noted in patients with uniparental disomy of the long arm of human chromosome 14 (UPD14). This suggests the presence of imprinted genes, consistent with observations of imprinting in the region of syntenic homology in the mouse. It is not known whether the distinct defects reported for paternal and maternal UPD14 are the result of biallelic expression or absence of expression of imprinted genes. Furthermore, identification of the genes responsible would be facilitated by a higher resolution map of the imprinted region(s) involved. Subjects with partial trisomy for chromosome 14 (Ts14) have been reported and hence also have an alteration in the dosage of their parental chromosomes. In this study, we have carried out genotype-phenotype correlations considering the parental origin of the extra chromosome in previously reported cases of maternal and paternal partial Ts14. The analysis has provided evidence of a correlation between distal maternal Ts14 and anomalies including low birth weight, short philtrum, and small hands. The clinical features found in the maternal and paternal trisomies are compared with those associated with maternal and paternal UPD14 and their significance is discussed in relation to genomic imprinting on chromosome 14. PMID:9783704

  9. Novel swine-origin influenza A virus in humans: another pandemic knocking at the door.

    PubMed

    Michaelis, Martin; Doerr, Hans Wilhem; Cinatl, Jindrich

    2009-08-01

    Influenza A viruses represent a continuous pandemic threat. In April 2009, a novel influenza A virus, the so-called swine-origin influenza A (H1N1) virus (S-OIV), was identified in Mexico. Although S-OIV originates from triple-reassortant swine influenza A (H1) that has been circulating in North American pig herds since the end of the 1990s, S-OIV is readily transmitted between humans but is not epidemic in pigs. After its discovery, S-OIV rapidly spread throughout the world within few weeks. In this review, we sum up the current situation and put it into the context of the current state of knowledge of influenza and influenza pandemics. Some indications suggest that a pandemic may be mild but even "mild" pandemics can result in millions of deaths. However, no reasonable forecasts how this pandemic may develop can be made at this time. Despite stockpiling by many countries and WHO, antiviral drugs will be limited in case of pandemic and resistances may emerge. Effective vaccines are regarded to be crucial for the control of influenza pandemics. However, production capacities are restricted and development/production of a S-OIV vaccine will interfere with manufacturing of seasonal influenza vaccines. The authors are convinced that S-OIV should be taken seriously as pandemic threat and underestimation of the menace by S-OIV to be by far more dangerous than its overestimation. PMID:19543913

  10. Identification of the Common Origins of Osteoclasts, Macrophages, and Dendritic Cells in Human Hematopoiesis

    PubMed Central

    Xiao, Yanling; Zijl, Sebastiaan; Wang, Liqin; de Groot, Daniel C.; van Tol, Maarten J.; Lankester, Arjan C.; Borst, Jannie

    2015-01-01

    Summary Osteoclasts (OCs) originate from the myeloid cell lineage, but the successive steps in their lineage commitment are ill-defined, especially in humans. To clarify OC origin, we sorted cell populations from pediatric bone marrow (BM) by flow cytometry and assessed their differentiation potential in vitro. Within the CD11b−CD34+c-KIT+ BM cell population, OC-differentiation potential was restricted to FLT3+ cells and enriched in an IL3 receptor (R)αhigh subset that constituted less than 0.5% of total BM. These IL3Rαhigh cells also generated macrophages (MΦs) and dendritic cells (DCs) but lacked granulocyte (GR)-differentiation potential, as demonstrated at the clonal level. The IL3Rαlow subset was re-defined as common progenitor of GR, MΦ, OC, and DC (GMODP) and gave rise to the IL3Rαhigh subset that was identified as common progenitor of MΦ, OC, and DC (MODP). Unbiased transcriptome analysis of CD11b−CD34+c-KIT+FLT3+ IL3Rαlow and IL3Rαhigh subsets corroborated our definitions of the GMODP and MODP and their developmental relationship. PMID:26004632

  11. Identification of the Common Origins of Osteoclasts, Macrophages, and Dendritic Cells in Human Hematopoiesis.

    PubMed

    Xiao, Yanling; Zijl, Sebastiaan; Wang, Liqin; de Groot, Daniel C; van Tol, Maarten J; Lankester, Arjan C; Borst, Jannie

    2015-06-01

    Osteoclasts (OCs) originate from the myeloid cell lineage, but the successive steps in their lineage commitment are ill-defined, especially in humans. To clarify OC origin, we sorted cell populations from pediatric bone marrow (BM) by flow cytometry and assessed their differentiation potential in vitro. Within the CD11b(-)CD34(+)c-KIT(+) BM cell population, OC-differentiation potential was restricted to FLT3(+) cells and enriched in an IL3 receptor (R)?(high) subset that constituted less than 0.5% of total BM. These IL3R?(high) cells also generated macrophages (M?s) and dendritic cells (DCs) but lacked granulocyte (GR)-differentiation potential, as demonstrated at the clonal level. The IL3R?(low) subset was re-defined as common progenitor of GR, M?, OC, and DC (GMODP) and gave rise to the IL3R?(high) subset that was identified as common progenitor of M?, OC, and DC (MODP). Unbiased transcriptome analysis of CD11b(-)CD34(+)c-KIT(+)FLT3(+) IL3R?(low) and IL3R?(high) subsets corroborated our definitions of the GMODP and MODP and their developmental relationship. PMID:26004632

  12. Massive parallel IGHV gene sequencing reveals a germinal center pathway in origins of human multiple myeloma

    PubMed Central

    Bryant, Dean; Seckinger, Anja; Hose, Dirk; Zojer, Niklas; Sahota, Surinder S.

    2015-01-01

    Human multiple myeloma (MM) is characterized by accumulation of malignant terminally differentiated plasma cells (PCs) in the bone marrow (BM), raising the question when during maturation neoplastic transformation begins. Immunoglobulin IGHV genes carry imprints of clonal tumor history, delineating somatic hypermutation (SHM) events that generally occur in the germinal center (GC). Here, we examine MM-derived IGHV genes using massive parallel deep sequencing, comparing them with profiles in normal BM PCs. In 4/4 presentation IgG MM, monoclonal tumor-derived IGHV sequences revealed significant evidence for intraclonal variation (ICV) in mutation patterns. IGHV sequences of 2/2 normal PC IgG populations revealed dominant oligoclonal expansions, each expansion also displaying mutational ICV. Clonal expansions in MM and in normal BM PCs reveal common IGHV features. In such MM, the data fit a model of tumor origins in which neoplastic transformation is initiated in a GC B-cell committed to terminal differentiation but still targeted by on-going SHM. Strikingly, the data parallel IGHV clonal sequences in some monoclonal gammopathy of undetermined significance (MGUS) known to display on-going SHM imprints. Since MGUS generally precedes MM, these data suggest origins of MGUS and MM with IGHV gene mutational ICV from the same GC B-cell, arising via a distinctive pathway. PMID:25929340

  13. Origins and evolutionary genomics of the novel swine-origin influenza A (H1N1) virus in humans--past and present perspectives.

    PubMed

    Mamun, M M A; Huda, A K M N

    2011-04-01

    Swine influenza viruses cause annual epidemics and occasional pandemics claiming the lives of millions from the early history up to the present days. This virus has drawn on a bag of evolutionary tricks to survive in one or another form in both humans and pigs with novel gene constellations through the periodic importation or exportation of viral genes. A prime example is emergence of pandemic novel swine-origin influenza A (H1N1) virus (S-OIV) in 2009 that have transmitted to and spread among humans, resulting in outbreaks internationally. The phylogenetic analysis of sequences of all genes of the S-OIV, showed that its genome contained six gene segments that were similar to ones previously found in triple-reassortant swine influenza viruses circulating in pigs in North America. The genes encoding neuraminidase and M protein were most closely related to those in influenza A viruses circulating in swine populations in Eurasia. This unique genetic combination of influenza virus gene segments leading to the emergence of novel S-OIV that had not been seen before in the world. Here, it has been used evolutionary analysis to estimate the timescale of the origins and the early development of the S-OIV epidemic. This paper shows that it was derived from several viruses circulating in swine and makes a briefly review over the origins and evolutionary genomics of current S-OIV in humans with historical perspectives with a view to exhibition of evolutionary relationship between past and present origins of swine influenza viruses. PMID:21467795

  14. Stone tool analysis and human origins research: some advice from Uncle Screwtape.

    PubMed

    Shea, John J

    2011-01-01

    The production of purposefully fractured stone tools with functional, sharp cutting edges is a uniquely derived hominin adaptation. In the long history of life on earth, only hominins have adopted this remarkably expedient and broadly effective technological strategy. In the paleontological record, flaked stone tools are irrefutable proof that hominins were present at a particular place and time. Flaked stone tools are found in contexts ranging from the Arctic to equatorial rainforests and on every continent except Antarctica. Paleolithic stone tools show complex patterns of variability, suggesting that they have been subject to the variable selective pressures that have shaped so many other aspects of hominin behavior and morphology. There is every reason to expect that insights gained from studying stone tools should provide vital and important information about the course of human evolution. And yet, one senses that archeological analyses of Paleolithic stone tools are not making as much of a contribution as they could to the major issues in human origins research. PMID:22034103

  15. Sulfur volatiles of microbial origin are key contributors to human-sensed truffle aroma.

    PubMed

    Splivallo, Richard; Ebeler, Susan E

    2015-03-01

    Truffles are symbiotic fungi in high demand for the aroma of their fruiting bodies which are colonized by a diverse microbial flora. Specific sulfur containing volatiles (thiophene derivatives) characteristic of the white truffle Tuber borchii were recently shown to be derived from the bacterial community inhabiting truffle fruiting bodies. Our aim here was to investigate whether thiophene derivatives contributed to the human-sensed aroma of T. borchii. Furthermore, we questioned whether the concentration of thiophene volatiles was affected by freezing or whether it differed in truffles from distinct geographical origins. Gas chromatography-olfactometry (GC-O) analysis revealed that thiophene derivatives were major contributors to the aroma of T. borchii. Of four thiophene derivatives detected in this study, 3-methyl-4,5-dihydrothiophene was the most important one in terms of its contribution to the overall aroma. The relative concentration of thiophene derivatives was unaffected by freezing; however, it differed in samples collected in distinct geographical locations (Italy versus New Zealand). The causes of this variability might be differences in storage conditions and/or in bacterial community composition of the fruiting bodies; however, further work is needed to confirm these hypotheses. Overall, our results demonstrate that thiophene derivatives are major contributors to the human-sensed aroma of T. borchii. PMID:25573471

  16. Many private mutations originate from the first few divisions of a human colorectal adenoma.

    PubMed

    Kang, Haeyoun; Salomon, Matthew P; Sottoriva, Andrea; Zhao, Junsong; Toy, Morgan; Press, Michael F; Curtis, Christina; Marjoram, Paul; Siegmund, Kimberly; Shibata, Darryl

    2015-11-01

    Intratumoural mutational heterogeneity (ITH) or the presence of different private mutations in different parts of the same tumour is commonly observed in human tumours. The mechanisms generating such ITH are uncertain. Here we find that ITH can be remarkably well structured by measuring point mutations, chromosome copy numbers, and DNA passenger methylation from opposite sides and individual glands of a 6 cm human colorectal adenoma. ITH was present between tumour sides and individual glands, but the private mutations were side-specific and subdivided the adenoma into two major subclones. Furthermore, ITH disappeared within individual glands because the glands were clonal populations composed of cells with identical mutant genotypes. Despite mutation clonality, the glands were relatively old, diverse populations when their individual cells were compared for passenger methylation and by FISH. These observations can be organized into an expanding star-like ancestral tree with co-clonal expansion, where many private mutations and multiple related clones arise during the first few divisions. As a consequence, most detectable mutational ITH in the final tumour originates from the first few divisions. Much of the early history of a tumour, especially the first few divisions, may be embedded within the detectable ITH of tumour genomes. PMID:26119426

  17. A unique Middle Miocene European hominoid and the origins of the great ape and human clade

    PubMed Central

    Moyà-Solà, Salvador; Alba, David M.; Almécija, Sergio; Casanovas-Vilar, Isaac; Köhler, Meike; De Esteban-Trivigno, Soledad; Robles, Josep M.; Galindo, Jordi; Fortuny, Josep

    2009-01-01

    The great ape and human clade (Primates: Hominidae) currently includes orangutans, gorillas, chimpanzees, bonobos, and humans. When, where, and from which taxon hominids evolved are among the most exciting questions yet to be resolved. Within the Afropithecidae, the Kenyapithecinae (Kenyapithecini + Equatorini) have been proposed as the sister taxon of hominids, but thus far the fragmentary and scarce Middle Miocene fossil record has hampered testing this hypothesis. Here we describe a male partial face with mandible of a previously undescribed fossil hominid, Anoiapithecus brevirostris gen. et sp. nov., from the Middle Miocene (11.9 Ma) of Spain, which enables testing this hypothesis. Morphological and geometric morphometrics analyses of this material show a unique facial pattern for hominoids. This taxon combines autapomorphic features—such as a strongly reduced facial prognathism—with kenyapithecine (more specifically, kenyapithecin) and hominid synapomorphies. This combination supports a sister-group relationship between kenyapithecins (Griphopithecus + Kenyapithecus) and hominids. The presence of both groups in Eurasia during the Middle Miocene and the retention in kenyapithecins of a primitive hominoid postcranial body plan support a Eurasian origin of the Hominidae. Alternatively, the two extant hominid clades (Homininae and Ponginae) might have independently evolved in Africa and Eurasia from an ancestral, Middle Miocene stock, so that the supposed crown-hominid synapomorphies might be homoplastic. PMID:19487676

  18. Can glycans unveil the origin of glycoprotein hormones? - human chorionic gonadotrophin as an example -.

    PubMed

    Ramírez-Llanelis, R; Llop, E; Ventura, R; Segura, J; Gutiérrez-Gallego, R

    2008-07-01

    Doping with (glyco)protein hormones represent an extremely challenging, analytical problem as nearly all are constitutively present at low concentrations that fluctuate according to circadian or alternative periodical, or external stimuli. Thus the mere concentration in a biological sample is only resolutive when this surpasses extreme values. As the vast majority of these molecules are produced by recombinant DNA technology it is believed that the exogenous molecules could bear the signature of the host cell. In particular, these could comprise structural differences originated from co or post-translational differences. In this study we have employed both proteomics and glycomics strategies to compare recombinant and urinary human chorionic gonadotrophin in order to evaluate this hypothesis. As anticipated the recombinant hormone could be shown to contain N-glycolyl neuraminic acid, a sialic acid that cannot be produced by humans. Furthermore, differences were observed in the overall glycosylation, in particular the presence of abundant hybrid-type glycans that were much less pronounced in the recombinant species. These differences were determined to occur predominantly in the alpha-subunit for which antidoping strategies focussed on these elements could be used for both chorionic gonadotrophin and lutrophin as they share the same alpha-subunit. PMID:18563855

  19. Probiotic and cultural characteristic of strain Lactobacillus gasseri 4/13 of human origin

    PubMed Central

    Baltova, Kalinka; Dimitrov, Zhechko

    2014-01-01

    Lactobacillus gasseri within the Lactobacillus acidophilus group is a major species in the human microflora. The potential probiotic properties of a L. gasseri strain of human origin were evaluated. Out of 17 studied L. gasseri strains, L. gasseri 4/13 showed the highest immunomodulatory effect (induction of interferon gamma measured by sandwich enzyme-linked immunosorbent assay) in Balb/c mouse splenocytes in vitro and the highest rate of adhesion to Caco-2 human epithelial cells. The strain also reduced the concentration of cholesterol in the growth medium by 65% as compared with the initial concentration (measured spectrophotometrically). These probiotic properties indicate that L. gasseri 4/13 could prove an attractive concentrated adjunct monoculture in the production of new functional foods. To obtain a freeze-dried bacterial concentrate from L. gasseri 4/13, the influence of different culture media, temperatures and pH values on the accumulation of cell biomass was studied. Yoghurt samples were produced using a classical fermentation technology. Freeze-dried concentrated monoculture of L. gasseri 4/13 with over 1 × 1010 CFU/g viable cells was added as an adjunct culture together with a starter. The viable L. gasseri 4/13 cells remained above the critical value of 106 CFU/g during storage at 5 °C for the entire 20-day period. Organoleptic tests did not reveal any adverse change in the product taste and aroma of yoghurt samples at the 20th day. In conclusion, L. gasseri 4/13 was selected as having suitable probiotic and cultural characteristics for production of fermented milk products with high nutritional and biological value. PMID:26692783

  20. The origin, global distribution, and functional impact of the human 8p23 inversion polymorphism

    PubMed Central

    Salm, Maximilian P.A.; Horswell, Stuart D.; Hutchison, Claire E.; Speedy, Helen E.; Yang, Xia; Liang, Liming; Schadt, Eric E.; Cookson, William O.; Wierzbicki, Anthony S.; Naoumova, Rossi P.; Shoulders, Carol C.

    2012-01-01

    Genomic inversions are an increasingly recognized source of genetic variation. However, a lack of reliable high-throughput genotyping assays for these structures has precluded a full understanding of an inversion's phylogenetic, phenotypic, and population genetic properties. We characterize these properties for one of the largest polymorphic inversions in man (the ∼4.5-Mb 8p23.1 inversion), a structure that encompasses numerous signals of natural selection and disease association. We developed and validated a flexible bioinformatics tool that utilizes SNP data to enable accurate, high-throughput genotyping of the 8p23.1 inversion. This tool was applied retrospectively to diverse genome-wide data sets, revealing significant population stratification that largely follows a clinal “serial founder effect” distribution model. Phylogenetic analyses establish the inversion's ancestral origin within the Homo lineage, indicating that 8p23.1 inversion has occurred independently in the Pan lineage. The human inversion breakpoint was localized to an inverted pair of human endogenous retrovirus elements within the large, flanking low-copy repeats; experimental validation of this breakpoint confirmed these elements as the likely intermediary substrates that sponsored inversion formation. In five data sets, mRNA levels of disease-associated genes were robustly associated with inversion genotype. Moreover, a haplotype associated with systemic lupus erythematosus was restricted to the derived inversion state. We conclude that the 8p23.1 inversion is an evolutionarily dynamic structure that can now be accommodated into the understanding of human genetic and phenotypic diversity. PMID:22399572

  1. The origin, global distribution, and functional impact of the human 8p23 inversion polymorphism.

    PubMed

    Salm, Maximilian P A; Horswell, Stuart D; Hutchison, Claire E; Speedy, Helen E; Yang, Xia; Liang, Liming; Schadt, Eric E; Cookson, William O; Wierzbicki, Anthony S; Naoumova, Rossi P; Shoulders, Carol C

    2012-06-01

    Genomic inversions are an increasingly recognized source of genetic variation. However, a lack of reliable high-throughput genotyping assays for these structures has precluded a full understanding of an inversion's phylogenetic, phenotypic, and population genetic properties. We characterize these properties for one of the largest polymorphic inversions in man (the ?4.5-Mb 8p23.1 inversion), a structure that encompasses numerous signals of natural selection and disease association. We developed and validated a flexible bioinformatics tool that utilizes SNP data to enable accurate, high-throughput genotyping of the 8p23.1 inversion. This tool was applied retrospectively to diverse genome-wide data sets, revealing significant population stratification that largely follows a clinal "serial founder effect" distribution model. Phylogenetic analyses establish the inversion's ancestral origin within the Homo lineage, indicating that 8p23.1 inversion has occurred independently in the Pan lineage. The human inversion breakpoint was localized to an inverted pair of human endogenous retrovirus elements within the large, flanking low-copy repeats; experimental validation of this breakpoint confirmed these elements as the likely intermediary substrates that sponsored inversion formation. In five data sets, mRNA levels of disease-associated genes were robustly associated with inversion genotype. Moreover, a haplotype associated with systemic lupus erythematosus was restricted to the derived inversion state. We conclude that the 8p23.1 inversion is an evolutionarily dynamic structure that can now be accommodated into the understanding of human genetic and phenotypic diversity. PMID:22399572

  2. Origin of germ cells and formation of new primary follicles in adult human ovaries

    PubMed Central

    Bukovsky, Antonin; Caudle, Michael R; Svetlikova, Marta; Upadhyaya, Nirmala B

    2004-01-01

    Recent reports indicate that functional mouse oocytes and sperm can be derived in vitro from somatic cell lines. We hypothesize that in adult human ovaries, mesenchymal cells in the tunica albuginea (TA) are bipotent progenitors with a commitment for both primitive granulosa and germ cells. We investigated ovaries of twelve adult women (mean age 32.8 ± 4.1 SD, range 27–38 years) by single, double, and triple color immunohistochemistry. We show that cytokeratin (CK)+ mesenchymal cells in ovarian TA differentiate into surface epithelium (SE) cells by a mesenchymal-epithelial transition. Segments of SE directly associated with ovarian cortex are overgrown by TA, forming solid epithelial cords, which fragment into small (20 micron) epithelial nests descending into the lower ovarian cortex, before assembling with zona pellucida (ZP)+ oocytes. Germ cells can originate from SE cells which cover the TA. Small (10 micron) germ-like cells showing PS1 meiotically expressed oocyte carbohydrate protein are derived from SE cells via asymmetric division. They show nuclear MAPK immunoexpression, subsequently divide symmetrically, and enter adjacent cortical vessels. During vascular transport, the putative germ cells increase to oocyte size, and are picked-up by epithelial nests associated with the vessels. During follicle formation, extensions of granulosa cells enter the oocyte cytoplasm, forming a single paranuclear CK+ Balbiani body supplying all the mitochondria of the oocyte. In the ovarian medulla, occasional vessels show an accumulation of ZP+ oocytes (25–30 microns) or their remnants, suggesting that some oocytes degenerate. In contrast to males, adult human female gonads do not preserve germline type stem cells. This study expands our previous observations on the formation of germ cells in adult human ovaries. Differentiation of primitive granulosa and germ cells from the bipotent mesenchymal cell precursors of TA in adult human ovaries represents a most sophisticated adaptive mechanism created during the evolution of female reproduction. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. An essential mission of such follicular turnover might be elimination of spontaneous or environmentally induced genetic alterations of oocytes in resting primary follicles. PMID:15115550

  3. Origin of germ cells and formation of new primary follicles in adult human ovaries.

    PubMed

    Bukovsky, Antonin; Caudle, Michael R; Svetlikova, Marta; Upadhyaya, Nirmala B

    2004-04-28

    Recent reports indicate that functional mouse oocytes and sperm can be derived in vitro from somatic cell lines. We hypothesize that in adult human ovaries, mesenchymal cells in the tunica albuginea (TA) are bipotent progenitors with a commitment for both primitive granulosa and germ cells. We investigated ovaries of twelve adult women (mean age 32.8 +/- 4.1 SD, range 27-38 years) by single, double, and triple color immunohistochemistry. We show that cytokeratin (CK)+ mesenchymal cells in ovarian TA differentiate into surface epithelium (SE) cells by a mesenchymal-epithelial transition. Segments of SE directly associated with ovarian cortex are overgrown by TA, forming solid epithelial cords, which fragment into small (20 micron) epithelial nests descending into the lower ovarian cortex, before assembling with zona pellucida (ZP)+ oocytes. Germ cells can originate from SE cells which cover the TA. Small (10 micron) germ-like cells showing PS1 meiotically expressed oocyte carbohydrate protein are derived from SE cells via asymmetric division. They show nuclear MAPK immunoexpression, subsequently divide symmetrically, and enter adjacent cortical vessels. During vascular transport, the putative germ cells increase to oocyte size, and are picked-up by epithelial nests associated with the vessels. During follicle formation, extensions of granulosa cells enter the oocyte cytoplasm, forming a single paranuclear CK+ Balbiani body supplying all the mitochondria of the oocyte. In the ovarian medulla, occasional vessels show an accumulation of ZP+ oocytes (25-30 microns) or their remnants, suggesting that some oocytes degenerate. In contrast to males, adult human female gonads do not preserve germline type stem cells. This study expands our previous observations on the formation of germ cells in adult human ovaries. Differentiation of primitive granulosa and germ cells from the bipotent mesenchymal cell precursors of TA in adult human ovaries represents a most sophisticated adaptive mechanism created during the evolution of female reproduction. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. An essential mission of such follicular turnover might be elimination of spontaneous or environmentally induced genetic alterations of oocytes in resting primary follicles. PMID:15115550

  4. The origin of novel avian influenza A (H7N9) and mutation dynamics for its human-to-human transmissible capacity.

    PubMed

    Peng, Jin; Yang, Hao; Jiang, Hua; Lin, Yi-xiao; Lu, Charles Damien; Xu, Ya-wei; Zeng, Jun

    2014-01-01

    In February 2013, H7N9 (A/H7N9/2013_China), a novel avian influenza virus, broke out in eastern China and caused human death. It is a global priority to discover its origin and the point in time at which it will become transmittable between humans. We present here an interdisciplinary method to track the origin of H7N9 virus in China and to establish an evolutionary dynamics model for its human-to-human transmission via mutations. After comparing influenza viruses from China since 1983, we established an A/H7N9/2013_China virus evolutionary phylogenetic tree and found that the human instances of virus infection were of avian origin and clustered into an independent line. Comparing hemagglutinin (HA) and neuraminidase (NA) gene sequences of A/H7N9/2013_China viruses with all human-to-human, avian, and swine influenza viruses in China in the past 30 years, we found that A/H7N9/2013_China viruses originated from Baer's Pochard H7N1 virus of Hu Nan Province 2010 (HA gene, EPI: 370846, similarity with H7N9 is 95.5%) and duck influenza viruses of Nanchang city 2000 (NA gene, EPI: 387555, similarity with H7N9 is 97%) through genetic re-assortment. HA and NA gene sequence comparison indicated that A/H7N9/2013_China virus was not similar to human-to-human transmittable influenza viruses. To simulate the evolution dynamics required for human-to-human transmission mutations of H7N9 virus, we employed the Markov model. The result of this calculation indicated that the virus would acquire properties for human-to-human transmission in 11.3 years (95% confidence interval (CI): 11.2-11.3, HA gene). PMID:24671138

  5. Human vs. animal outbreaks of the 2009 swine-origin H1N1 influenza A epidemic.

    PubMed

    Scotch, Matthew; Brownstein, John S; Vegso, Sally; Galusha, Deron; Rabinowitz, Peter

    2011-09-01

    The majority of emerging infectious diseases are zoonotic in origin, including recently emerging influenza viruses such as the 2009 swine-origin H1N1 influenza A epidemic. The epidemic that year affected both human and animal populations as it spread globally. In fact, before the end of 2009, 14 different countries reported H1N1 infected swine. In order to better understand the zoonotic nature of the epidemic and the relationship between human and animal disease surveillance data streams, we compared 2009 reports of H1N1 infection to define the temporal relationship between reported cases in animals and humans. Generally, human cases preceded animal cases at a country-level, supporting the potential of H1N1 infection to be a "reverse zoonosis", and the value of integrating human and animal disease report data. PMID:21912985

  6. The Inquiring Eye: Early Modernism.

    ERIC Educational Resources Information Center

    Wisotzki, Paula

    This teaching guide introduces students to early 20th century European and American art. Through critically viewing and discussing art images and participating in related activities, students are encouraged to explore the historical and cultural context within which the art was created. This guide includes background information and an overview…

  7. Early-Modern "Speech" Marks

    ERIC Educational Resources Information Center

    Blackburn, Nick

    2011-01-01

    This essay presents a revised history of the punctuation mark ["], drawn from the earliest communities who made it their own. By situating the development of ["] in its historical context, from first uses of the diple [diple] by the Greek scholar Aristarchus, it explains how it was the general applications which persisted into the sixteenth…

  8. Tracing the origins of Mycobacterium bovis tuberculosis in humans in the USA to cattle in Mexico using spoligotyping☆

    PubMed Central

    Rodwell, Timothy C.; Kapasi, Anokhi J.; Moore, Marisa; Milian-Suazo, Feliciano; Harris, Beth; Guerrero, L.P.; Moser, Kathleen; Strathdee, Steffanie A.; Garfein, Richard S.

    2010-01-01

    Objectives To compare genotypes of Mycobacterium bovis strains from humans in Southern California with genotypes of M. bovis strains in cattle in Mexico and the USA to explore the possible origins of human infections. Methods We conducted a descriptive analysis of M. bovis genotypes from a binational population of humans and cattle using spacer oligonucleotide typing (spoligotyping). Results One hundred six human M. bovis spoligotypes were compared to spoligotypes from 496 Mexican cattle and 219 US cattle. Twelve spoligotype patterns were identified among human cases and 126 spoligotype patterns were detected in cattle. Over 91% (97/106) of the human M. bovis isolates had spoligotypes that were identical to those found in Mexican cattle. Four human cases had spoligotypes that matched both cattle born in Mexico and in the USA. Nine human cases had spoligotypes that did not match cattle born in Mexico or the USA. Conclusions Our data indicate that the population of M. bovis strains causing human TB disease in Southern California is closely related to the M. bovis strain population found in Mexican cattle and supports existing epidemiological evidence that human M. bovis disease in San Diego likely originated from Mexican cattle. PMID:20399697

  9. The Social Origins of Sustained Attention in One-Year-Old Human Infants.

    PubMed

    Yu, Chen; Smith, Linda B

    2016-05-01

    The ability to sustain attention is a major achievement in human development and is generally believed to be the developmental product of increasing self-regulatory and endogenous (i.e., internal, top-down, voluntary) control over one's attention and cognitive systems [1-5]. Because sustained attention in late infancy is predictive of future development, and because early deficits in sustained attention are markers for later diagnoses of attentional disorders [6], sustained attention is often viewed as a constitutional and individual property of the infant [6-9]. However, humans are social animals; developmental pathways for seemingly non-social competencies evolved within the social group and therefore may be dependent on social experience [10-13]. Here, we show that social context matters for the duration of sustained attention episodes in one-year-old infants during toy play. Using head-mounted eye tracking to record moment-by-moment gaze data from both parents and infants, we found that when the social partner (parent) visually attended to the object to which infant attention was directed, infants, after the parent's look, extended their duration of visual attention to the object. Looks to the same object by two social partners is a well-studied phenomenon known as joint attention, which has been shown to be critical to early learning and to the development of social skills [14, 15]. The present findings implicate joint attention in the development of the child's own sustained attention and thus challenge the current understanding of the origins of individual differences in sustained attention, providing a new and potentially malleable developmental pathway to the self-regulation of attention. PMID:27133869

  10. Human origins and the transition from promiscuity to pair-bonding

    PubMed Central

    Gavrilets, Sergey

    2012-01-01

    A crucial step in recent theories of human origins is the emergence of strong pair-bonding between males and females accompanied by a dramatic reduction in the male-to-male conflict over mating and an increased investment in offspring. How such a transition from promiscuity to pair-bonding could be achieved is puzzling. Many species would, indeed, be much better off evolutionarily if the effort spent on male competition over mating was redirected to increasing female fertility or survivorship of offspring. Males, however, are locked in a “social dilemma,” where shifting one’s effort from “appropriation” to “production” would give an advantage to free-riding competitors and therefore, should not happen. Here, I first consider simple models for four prominent scenarios of the human transition to pair-bonding: communal care, mate guarding, food for mating, and mate provisioning. I show that the transition is not feasible under biologically relevant conditions in any of these models. Then, I show that the transition can happen if one accounts for male heterogeneity, assortative pair formation, and evolution of female choice and faithfulness. This process is started when low-ranked males begin using an alternative strategy of female provisioning. At the end, except for the top-ranked individuals, males invest exclusively in provisioning females who have evolved very high fidelity to their mates. My results point to the crucial importance of female choice and emphasize the need for incorporating between-individual variation in theoretical and empirical studies of social dilemmas and behaviors. PMID:22645330

  11. Meiotic Nondisjunction: Insights into the Origin and Significance of Aneuploidy in Human Spermatozoa.

    PubMed

    Ioannou, Dimitrios; Tempest, Helen G

    2015-01-01

    Chromosome aneuploidy refers to changes in the chromosome complement of a genome and can include gain or loss of genetic material. The human genome is delicately balanced, and for the most part perturbations in the chromosome complement are often incompatible with embryonic development. The importance and clinical relevance of paternally derived aneuploidy is often overshadowed by the large maternal contribution; as a result, the paternal contribution to pregnancy loss due to chromosome aneuploidy is rarely considered within the clinic. However, there is increasing evidence to suggest that certain men have significantly higher levels of sperm aneuploidy, which is mirrored by an increase in aneuploidy within their embryos and offspring. Therefore, the paternal contribution to aneuploidy at least for some individuals may have greater clinical significance than is currently perceived. Thus, the main focus of this chapter is to provide insights into the origin and clinical relevance of paternally derived aneuploidy. Furthermore, this section will review the general mechanisms through which aneuploidy arises during spermatogenesis and how numerical (whole chromosome) and structural chromosome aberrations (cytogenetically visible or submicroscopic) may lead to clinically relevant aneuploidy potentially resulting in pregnancy loss, congenital malformations, and cognitive impairment. PMID:26178843

  12. Human T helper type 1 dichotomy: origin, phenotype and biological activities

    PubMed Central

    Annunziato, Francesco; Cosmi, Lorenzo; Liotta, Francesco; Maggi, Enrico; Romagnani, Sergio

    2015-01-01

    The great variety of pathogens present in the environment has obliged the immune system to evolve different mechanisms for tailored and maximally protective responses. Initially, two major types of CD4+ T helper (Th) effector cells were identified, and named as type 1 (Th1) and type 2 (Th2) cells because of the different cytokines they produce. More recently, a third type of CD4+ Th effectors has been identified and named as Th17 cells. Th17 cells, however, have been found to exhibit high plasticity because they rapidly shift into the Th1 phenotype in the inflammatory sites. Therefore, in these sites there is usually a dichotomous mixture of classic and non-classic (Th17-derived) Th1 cells. In humans, non-classic Th1 cells express CD161, as well as the retinoic acid orphan receptor C, interleukin-17 receptor E (IL-17RE), IL-1RI, CCR6, and IL-4-induced gene 1 and Tob-1, which are all virtually absent from classic Th1 cells. The possibility to distinguish between these two cell subsets may allow the opportunity to better establish their respective pathogenic role in different chronic inflammatory disorders. In this review, we discuss the different origin, the distinctive phenotypic features and the major biological activities of classic and non-classic Th1 cells. PMID:25284714

  13. Social Origins of Rhythm? Synchrony and Temporal Regularity in Human Vocalization

    PubMed Central

    Bowling, Daniel L.; Herbst, Christian T.; Fitch, W. Tecumseh

    2013-01-01

    Humans have a capacity to perceive and synchronize with rhythms. This is unusual in that only a minority of other species exhibit similar behavior. Study of synchronizing species (particularly anurans and insects) suggests that simultaneous signal production by different individuals may play a critical role in the development of regular temporal signaling. Accordingly, we investigated the link between simultaneous signal production and temporal regularity in our own species. Specifically, we asked whether inter-individual synchronization of a behavior that is typically irregular in time, speech, could lead to evenly-paced or “isochronous” temporal patterns. Participants read nonsense phrases aloud with and without partners, and we found that synchronous reading resulted in greater regularity of durational intervals between words. Comparison of same-gender pairings showed that males and females were able to synchronize their temporal speech patterns with equal skill. These results demonstrate that the shared goal of synchronization can lead to the development of temporal regularity in vocalizations, suggesting that the origins of musical rhythm may lie in cooperative social interaction rather than in sexual selection. PMID:24312214

  14. A Revised Root for the Human Y Chromosomal Phylogenetic Tree: The Origin of Patrilineal Diversity in Africa

    PubMed Central

    Cruciani, Fulvio; Trombetta, Beniamino; Massaia, Andrea; Destro-Bisol, Giovanni; Sellitto, Daniele; Scozzari, Rosaria

    2011-01-01

    To shed light on the structure of the basal backbone of the human Y chromosome phylogeny, we sequenced about 200 kb of the male-specific region of the human Y chromosome (MSY) from each of seven Y chromosomes belonging to clades A1, A2, A3, and BT. We detected 146 biallelic variant sites through this analysis. We used these variants to construct a patrilineal tree, without taking into account any previously reported information regarding the phylogenetic relationships among the seven Y chromosomes here analyzed. There are several key changes at the basal nodes as compared with the most recent reference Y chromosome tree. A different position of the root was determined, with important implications for the origin of human Y chromosome diversity. An estimate of 142 KY was obtained for the coalescence time of the revised MSY tree, which is earlier than that obtained in previous studies and easier to reconcile with plausible scenarios of modern human origin. The number of deep branchings leading to African-specific clades has doubled, further strengthening the MSY-based evidence for a modern human origin in the African continent. An analysis of 2204 African DNA samples showed that the deepest clades of the revised MSY phylogeny are currently found in central and northwest Africa, opening new perspectives on early human presence in the continent. PMID:21601174

  15. ['Charitable brothers' in charge of hospitals in early modern times: The hospital in Linz/Austria and its patients up to c. 1780].

    PubMed

    Watzka, Carlos

    2008-01-01

    The article deals with the history of the Hospital of the Brothers of St. John of God (in German: "Barmherzige Brüder"; official name "Ordo Hospitalarius Sancti Joannis a Deo") in the capital of Upper Austria, Linz, from its founding in 1757 to c. 1780. Primarily, the organisational development and the patients of the institute are discussed. The order's hospital already functioned as a medical hospital for the treatment of acute diseases: It was oriented towards the reestablishment of health of its inmates during short time and offered treatment by a staff of learned medical experts, among them academically trained physicians. The accommodation of the patients yet took place in a largely undifferentiated manner, as most of them were situated in a large common hall. This was obviously a consequence of the comparatively little capacity of the organisation, too, which sustained about 12 beds in the beginning, and about 20 around 1780. Nonetheless, the number of patients treated there summed up to nearly 1% of the entire male population of Upper Austria even during the first decade of its existence. In early modern time, only men were admitted to this hospital, the average age of them being only ca. 30 years. As far as social status is concerned, most of them (according to a representative sample out of the admissions of 1757-1767) were handicraftsmen (more than two thirds), labourers and servants. Thus, the organisation was obviously destined to broad social strata, but by no way displays itself as a poorhouse. Average annual mortality was 10 to 13%, which is comparable to that of other hospitals of the order in 18th century Austria. Most of the admitted persons suffered from "fever" or inner diseases and were dismissed as healed already after some weeks of stay. PMID:19830956

  16. Out of Africa and into an ice age: on the role of global climate change in the late Pleistocene migration of early modern humans out of Africa.

    PubMed

    Carto, Shannon L; Weaver, Andrew J; Hetherington, Renée; Lam, Yin; Wiebe, Edward C

    2009-02-01

    The results from two climate model simulations are used to explore the relationship between North Atlantic sea surface temperatures and the development of African aridity around 100,000 years ago. Through the use of illustrative simulations with an Earth System Climate Model, it is shown that freshwater fluxes associated with ice sheet surges into the North Atlantic, known as Heinrich events, lead to the southward shift of the intertropical convergence zone over Africa. This, combined with the overall increased aridity in the cooler mean climate, leads to substantial changes in simulated African vegetation cover, particularly in the Sahel. We suggest that Heinrich events, which occurred episodically throughout the last glacial cycle, led to abrupt changes in climate that may have rendered large parts of North, East, and West Africa unsuitable for hominin occupation, thus compelling early Homo sapiens to migrate out of Africa. PMID:19019409

  17. Trends in antimicrobial resistance phenotypes in non-typhoid Salmonellae from human and poultry origins in France.

    PubMed

    Cailhol, J; Lailler, R; Bouvet, P; La Vieille, S; Gauchard, F; Sanders, P; Brisabois, A

    2006-02-01

    A total of 1873 strains from human origin and 4283 strains from non-human origin of Salmonella enterica serotypes Typhimurium, Enteritidis, Heidelberg, Hadar and Virchow, collected over three years 1993, 1997 and 2000, were examined in order to determine the rate of antimicrobial resistance to 12 antimicrobial drugs. The objective of the study was to describe and to compare the evolution of the main resistance types in human and non-human isolates, focusing on the poultry sector. The evolution and the rates of antimicrobial resistances for the five serotypes, with the exception of Virchow, were almost comparable in strains isolated from human and non-human sources over the period studied. The most striking result concerning single resistance was the spectacular increase of the resistance frequency to nalidixic acid for the strains belonging to serotypes Hadar and Virchow, especially in the poultry food sector (14% in 1993 vs. 72% in 2000 for Salmonella Virchow, 4% in 1993 vs. 70% in 2000 for Salmonella Hadar) and also in human isolates (24% in 1997 vs. 48% in 2000 for S. Virchow, 31% in 1997 vs. 78% in 2000 for S. Hadar). In addition to the classical resistance to ampicillin, streptomycin, sulphonamide, chloramphenicol and tetracycline (ASSuCT resistance type), which stabilized between 1997 and 2000, the emergence of a new resistance type was observed. PMID:16409665

  18. Believe it or not: Moving non-biological stimuli believed to have human origin can be represented as human movement.

    PubMed

    Gowen, E; Bolton, E; Poliakoff, E

    2016-01-01

    Does our brain treat non-biological movements (e.g. moving abstract shapes or robots) in the same way as human movements? The current work tested whether the movement of a non-biological rectangular object, believed to be based on a human action is represented within the observer's motor system. A novel visuomotor priming task was designed to pit true imitative compatibility, due to human action representation against more general stimulus response compatibility that has confounded previous belief experiments. Stimulus response compatibility effects were found for the object. However, imitative compatibility was found when participants repeated the object task with the belief that the object was based on a human finger movement, and when they performed the task viewing a real human hand. These results provide the first demonstration that non-biological stimuli can be represented as a human movement if they are believed to have human agency and have implications for interactions with technology and robots. PMID:26550801

  19. Relationship Between Human Physiological Parameters And Geomagnetic Variations Of Solar Origin

    NASA Astrophysics Data System (ADS)

    Dimitrova, S.

    This study attempts to assess the influence of increased geomagnetic activity on some human physiological parameters. The blood pressure, heart rate and general well-being of 86 volunteers were measured (the latter by means of a standardized questionnaire) on work days in autumn 2001 (01/10 to 09/11) and in spring 2002 (08/04 to 28/05). These periods were chosen because of maximal expected geomagnetic activity. Altogether, 2799 recordings were obtained and analysed. MANOVA was employed to check the significance of the influence of three factors on the physiological parameters under consideration. The three factors were the following: 1) planetary geomagnetic activity level estimated by Ap-index and divided into five levels; 2) gender - males and females; 3) blood pressure degree - persons in the group examined were divided into hypotensive, normotensive and hypertensive. Post hoc analysis was performed to elicit the significance of differences in the factors' levels. The average arterial blood pressure of the group was found to increase significantly with the increase of geomagnetic activity level. The average increment of systolic and diastolic blood pressure reached 9%, which deserves attention from a medical point of view. This effect was present irrespectively of gender. Results obtained suppose that hypertensive persons have the highest sensitivity and the hypotensive persons have the lowest sensitivity of the arterial blood pressure to increase of geomagnetic activity. The results did not show significant changes in the heart rate. The percentage of the persons who reported subjective psycho-physiological complaints was also found to increase significantly with the geomagnetic activity increase. During severe geomagnetic storms 30% of the persons examined reported subjective complaints and the highest sensitivity was revealed for the hypertensive females. The results obtained add further evidence that blood pressure seems to be affected by geomagnetic variations of solar origin. The examinations and analyses performed show that space weather prediction may be utilized for the purpose of pharmacological and regime measures to limit the adverse physiological reactions to geomagnetic storms.

  20. Origin & Evolution of the Grand Forks Human Nutrition Research Center, 1970-90

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the early 1960s William E Cornatzer, MD, PhD, suggested the need for increased USDA research concerning human nutrition, and creation of the Grand Forks Human Nutrition Laboratory (Grand Forks Human Nutrition Research Center). He shared ideas with Senator Milton R. Young of North Dakota, who requ...

  1. Human Genetic Ancestral Composition Correlates with the Origin of Mycobacterium leprae Strains in a Leprosy Endemic Population

    PubMed Central

    Cardona-Castro, Nora; Cortés, Edwin; Beltrán, Camilo; Romero, Marcela; Badel-Mogollón, Jaime E.; Bedoya, Gabriel

    2015-01-01

    Recent reports have suggested that leprosy originated in Africa, extended to Asia and Europe, and arrived in the Americas during European colonization and the African slave trade. Due to colonization, the contemporary Colombian population is an admixture of Native-American, European and African ancestries. Because microorganisms are known to accompany humans during migrations, patterns of human migration can be traced by examining genomic changes in associated microbes. The current study analyzed 118 leprosy cases and 116 unrelated controls from two Colombian regions endemic for leprosy (Atlantic and Andean) in order to determine possible associations of leprosy with patient ancestral background (determined using 36 ancestry informative markers), Mycobacterium leprae genotype and/or patient geographical origin. We found significant differences between ancestral genetic composition. European components were predominant in Andean populations. In contrast, African components were higher in the Atlantic region. M. leprae genotypes were then analyzed for cluster associations and compared with the ancestral composition of leprosy patients. Two M. leprae principal clusters were found: haplotypes C54 and T45. Haplotype C54 associated with African origin and was more frequent in patients from the Atlantic region with a high African component. In contrast, haplotype T45 associated with European origin and was more frequent in Andean patients with a higher European component. These results suggest that the human and M. leprae genomes have co-existed since the African and European origins of the disease, with leprosy ultimately arriving in Colombia during colonization. Distinct M. leprae strains followed European and African settlement in the country and can be detected in contemporary Colombian populations. PMID:26360617

  2. Human Genetic Ancestral Composition Correlates with the Origin of Mycobacterium leprae Strains in a Leprosy Endemic Population.

    PubMed

    Cardona-Castro, Nora; Cortés, Edwin; Beltrán, Camilo; Romero, Marcela; Badel-Mogollón, Jaime E; Bedoya, Gabriel

    2015-01-01

    Recent reports have suggested that leprosy originated in Africa, extended to Asia and Europe, and arrived in the Americas during European colonization and the African slave trade. Due to colonization, the contemporary Colombian population is an admixture of Native-American, European and African ancestries. Because microorganisms are known to accompany humans during migrations, patterns of human migration can be traced by examining genomic changes in associated microbes. The current study analyzed 118 leprosy cases and 116 unrelated controls from two Colombian regions endemic for leprosy (Atlantic and Andean) in order to determine possible associations of leprosy with patient ancestral background (determined using 36 ancestry informative markers), Mycobacterium leprae genotype and/or patient geographical origin. We found significant differences between ancestral genetic composition. European components were predominant in Andean populations. In contrast, African components were higher in the Atlantic region. M. leprae genotypes were then analyzed for cluster associations and compared with the ancestral composition of leprosy patients. Two M. leprae principal clusters were found: haplotypes C54 and T45. Haplotype C54 associated with African origin and was more frequent in patients from the Atlantic region with a high African component. In contrast, haplotype T45 associated with European origin and was more frequent in Andean patients with a higher European component. These results suggest that the human and M. leprae genomes have co-existed since the African and European origins of the disease, with leprosy ultimately arriving in Colombia during colonization. Distinct M. leprae strains followed European and African settlement in the country and can be detected in contemporary Colombian populations. PMID:26360617

  3. Human interleukin 17–producing cells originate from a CD161+CD4+ T cell precursor

    PubMed Central

    Cosmi, Lorenzo; De Palma, Raffaele; Santarlasci, Veronica; Maggi, Laura; Capone, Manuela; Frosali, Francesca; Rodolico, Gabriella; Querci, Valentina; Abbate, Gianfranco; Angeli, Roberta; Berrino, Liberato; Fambrini, Massimiliano; Caproni, Marzia; Tonelli, Francesco; Lazzeri, Elena; Parronchi, Paola; Liotta, Francesco; Maggi, Enrico; Romagnani, Sergio; Annunziato, Francesco

    2008-01-01

    We demonstrate that CD161 is a highly up-regulated gene in human interleukin (IL) 17 T helper cell (Th17) clones and that all IL-17–producing cells are contained in the CD161+ fraction of CD4+ T cells present in the circulation or in inflamed tissues, although they are not CD1-restricted natural killer T cells. More importantly, we show that all IL-17–producing cells originate from CD161+ naive CD4+ T cells of umbilical cord blood, as well as of the postnatal thymus, in response to the combined activity of IL-1β and IL-23. These findings implicate CD161 as a novel surface marker for human Th17 cells and demonstrate the exclusive origin of these cells from a CD161+CD4+ T cell progenitor. PMID:18663128

  4. Genetic relatedness between Japanese and European isolates of Clostridium difficile originating from piglets and their risk associated with human health

    PubMed Central

    Usui, Masaru; Nanbu, Yukie; Oka, Kentaro; Takahashi, Motomichi; Inamatsu, Takashi; Asai, Tetsuo; Kamiya, Shigeru; Tamura, Yutaka

    2014-01-01

    Clostridium difficile colonization in pig intestine has been a public health concern. We analyzed C. difficile prevalence among piglets in Japan to clarify their origin and extent of the associated risk by using molecular and microbiological methods for both swine and human clinical isolates and foreign isolates. C. difficile was isolated from 120 neonatal piglet fecal samples. Toxin gene profile, antimicrobial susceptibilities, PCR ribotype, and multiple-locus variable-number tandem-repeat analysis (MLVA) type of swine isolates were determined and compared with those of human clinical and foreign isolates. One-hundred C. difficile strains were isolated from 69 (57.5%) samples, and 61 isolates (61%) were toxin gene-positive. Some isolates were resistant to antimicrobials, contributing to antibiotic-associated diarrhea by C. difficile. These results suggest that C. difficile, prevalent among Japanese pigs, is a potential risk for antibiotic-associated diarrhea. Furthermore, PCR ribotype 078 (12 isolates), which has been linked to multiple outbreaks worldwide, was the third-most frequently isolated of the 14 PCR ribotypes identified. Moreover, MLVA revealed that all 12 PCR ribotype 078 isolates were genetically related to European PCR ribotype 078 strains found in both humans and pigs. To date, in Japan, many breeding pigs have been imported from European countries. The genetic relatedness of C. difficile isolates of Japanese swine origin to those of European origin suggests that they were introduced into Japan via imported pigs. PMID:25339943

  5. Genetic relatedness between Japanese and European isolates of Clostridium difficile originating from piglets and their risk associated with human health.

    PubMed

    Usui, Masaru; Nanbu, Yukie; Oka, Kentaro; Takahashi, Motomichi; Inamatsu, Takashi; Asai, Tetsuo; Kamiya, Shigeru; Tamura, Yutaka

    2014-01-01

    Clostridium difficile colonization in pig intestine has been a public health concern. We analyzed C. difficile prevalence among piglets in Japan to clarify their origin and extent of the associated risk by using molecular and microbiological methods for both swine and human clinical isolates and foreign isolates. C. difficile was isolated from 120 neonatal piglet fecal samples. Toxin gene profile, antimicrobial susceptibilities, PCR ribotype, and multiple-locus variable-number tandem-repeat analysis (MLVA) type of swine isolates were determined and compared with those of human clinical and foreign isolates. One-hundred C. difficile strains were isolated from 69 (57.5%) samples, and 61 isolates (61%) were toxin gene-positive. Some isolates were resistant to antimicrobials, contributing to antibiotic-associated diarrhea by C. difficile. These results suggest that C. difficile, prevalent among Japanese pigs, is a potential risk for antibiotic-associated diarrhea. Furthermore, PCR ribotype 078 (12 isolates), which has been linked to multiple outbreaks worldwide, was the third-most frequently isolated of the 14 PCR ribotypes identified. Moreover, MLVA revealed that all 12 PCR ribotype 078 isolates were genetically related to European PCR ribotype 078 strains found in both humans and pigs. To date, in Japan, many breeding pigs have been imported from European countries. The genetic relatedness of C. difficile isolates of Japanese swine origin to those of European origin suggests that they were introduced into Japan via imported pigs. PMID:25339943

  6. ANIMAL PATHOGENS THAT MAY CAUSE HUMAN DISEASE THAT ORIGINATE FROM FARM OPERATIONS

    EPA Science Inventory

    The recent increase in concentrated animal feeding operations in the United States has caused renewed concern regarding the infectious diseases that may be passed from farm animals to humans via the environment. It is also known that more than 20 recent epidemics among humans cou...

  7. Introductions and evolution of human-origin seasonal influenza A viruses in multinational swine populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The capacity of influenza A viruses to cross species barriers presents a continual threat to human and animal health. Knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. We sequenced the genomes of 141 influen...

  8. Origin of human chromosome 2: An ancestral telomere-telomere fusion

    SciTech Connect

    Ijdo, J.W.; Baldini, A.; Ward, D.C.; Reeders, S.T.; Wells, R.A. )

    1991-10-15

    The authors identified two allelic genomic cosmids from human chromosome 2, c8.1 and c29B, each containing two inverted arrays of the vertebrate telomeric repeat in a head-to-head arrangement, 5{prime}(TTAGGG){sub n}-(CCCTAA){sub m}3{prime}. Sequences flanking this telomeric repeat are characteristic of present-day human pretelomeres. BAL-31 nuclease experiments with yeast artificial chromosome clones of human telomeres and fluorescence in situ hybridization reveal that sequences flanking these inverted repeats hybridize both to band 2q13 and to different, but overlapping, subsets of human chromosome ends. They conclude that the locus cloned in cosmids c8.1 and c29B is the relic of an ancient telomere-telomere fusion and marks the point at which two ancestral ape chromosomes fused to give rise to human chromosome 2.

  9. The relationship between the human state and external perturbations of atmospheric, geomagnetic and solar origin

    NASA Astrophysics Data System (ADS)

    Gavryuseva, E.; Kroussanova, N.

    2002-12-01

    The relationship between the state of human body and the external factors such as the different phenomena of solar activity, geomagnetic perturbations and local atmospheric characteristics is studied. The monitoring of blood pressure and electro-conductivity of human body in acupuncture points for a group fo 28 people over the period of 1.5 year has been performed daily from February 2001 to August 2002 in Capodimonte Observatory in Naples, Italy. The modified Voll method of electropuncture diagnostics was used. The strong correlation between the human body state and meteo conditions is found and the probable correlation with geomagnetic perturbations is discussed.

  10. Origin of human bipedalism as an adaptation for locomotion on flexible branches.

    PubMed

    Thorpe, S K S; Holder, R L; Crompton, R H

    2007-06-01

    Human bipedalism is commonly thought to have evolved from a quadrupedal terrestrial precursor, yet some recent paleontological evidence suggests that adaptations for bipedalism arose in an arboreal context. However, the adaptive benefit of arboreal bipedalism has been unknown. Here we show that it allows the most arboreal great ape, the orangutan, to access supports too flexible to be negotiated otherwise. Orangutans react to branch flexibility like humans running on springy tracks, by increasing knee and hip extension, whereas all other primatesdothe reverse. Human bipedalism is thus less an innovation than an exploitation of a locomotor behavior retained from the common great ape ancestor. PMID:17540902

  11. Voice Modulation: A Window into the Origins of Human Vocal Control?

    PubMed

    Pisanski, Katarzyna; Cartei, Valentina; McGettigan, Carolyn; Raine, Jordan; Reby, David

    2016-04-01

    An unresolved issue in comparative approaches to speech evolution is the apparent absence of an intermediate vocal communication system between human speech and the less flexible vocal repertoires of other primates. We argue that humans' ability to modulate nonverbal vocal features evolutionarily linked to expression of body size and sex (fundamental and formant frequencies) provides a largely overlooked window into the nature of this intermediate system. Recent behavioral and neural evidence indicates that humans' vocal control abilities, commonly assumed to subserve speech, extend to these nonverbal dimensions. This capacity appears in continuity with context-dependent frequency modulations recently identified in other mammals, including primates, and may represent a living relic of early vocal control abilities that led to articulated human speech. PMID:26857619

  12. Tracking the evolutionary origins of dog-human cooperation: the “Canine Cooperation Hypothesis”

    PubMed Central

    Range, Friederike; Virányi, Zsófia

    2015-01-01

    At present, beyond the fact that dogs can be easier socialized with humans than wolves, we know little about the motivational and cognitive effects of domestication. Despite this, it has been suggested that during domestication dogs have become socially more tolerant and attentive than wolves. These two characteristics are crucial for cooperation, and it has been argued that these changes allowed dogs to successfully live and work with humans. However, these domestication hypotheses have been put forward mainly based on dog-wolf differences reported in regard to their interactions with humans. Thus, it is possible that these differences reflect only an improved capability of dogs to accept humans as social partners instead of an increase of their general tolerance, attentiveness and cooperativeness. At the Wolf Science Center, in order to detangle these two explanations, we raise and keep dogs and wolves similarly socializing them with conspecifics and humans and then test them in interactions not just with humans but also conspecifics. When investigating attentiveness toward human and conspecific partners using different paradigms, we found that the wolves were at least as attentive as the dogs to their social partners and their actions. Based on these findings and the social ecology of wolves, we propose the Canine Cooperation Hypothesis suggesting that wolves are characterized with high social attentiveness and tolerance and are highly cooperative. This is in contrast with the implications of most domestication hypotheses about wolves. We argue, however, that these characteristics of wolves likely provided a good basis for the evolution of dog-human cooperation. PMID:25642203

  13. Tracking the evolutionary origins of dog-human cooperation: the "Canine Cooperation Hypothesis".

    PubMed

    Range, Friederike; Virányi, Zsófia

    2014-01-01

    At present, beyond the fact that dogs can be easier socialized with humans than wolves, we know little about the motivational and cognitive effects of domestication. Despite this, it has been suggested that during domestication dogs have become socially more tolerant and attentive than wolves. These two characteristics are crucial for cooperation, and it has been argued that these changes allowed dogs to successfully live and work with humans. However, these domestication hypotheses have been put forward mainly based on dog-wolf differences reported in regard to their interactions with humans. Thus, it is possible that these differences reflect only an improved capability of dogs to accept humans as social partners instead of an increase of their general tolerance, attentiveness and cooperativeness. At the Wolf Science Center, in order to detangle these two explanations, we raise and keep dogs and wolves similarly socializing them with conspecifics and humans and then test them in interactions not just with humans but also conspecifics. When investigating attentiveness toward human and conspecific partners using different paradigms, we found that the wolves were at least as attentive as the dogs to their social partners and their actions. Based on these findings and the social ecology of wolves, we propose the Canine Cooperation Hypothesis suggesting that wolves are characterized with high social attentiveness and tolerance and are highly cooperative. This is in contrast with the implications of most domestication hypotheses about wolves. We argue, however, that these characteristics of wolves likely provided a good basis for the evolution of dog-human cooperation. PMID:25642203

  14. A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans

    PubMed Central

    Chua, Kaw Bing; Crameri, Gary; Hyatt, Alex; Yu, Meng; Tompang, Mohd Rosli; Rosli, Juliana; McEachern, Jennifer; Crameri, Sandra; Kumarasamy, Verasingam; Eaton, Bryan T.; Wang, Lin-Fa

    2007-01-01

    Respiratory infections constitute the most widespread human infectious disease, and a substantial proportion of them are caused by unknown etiological agents. Reoviruses (respiratory enteric orphan viruses) were first isolated from humans in the early 1950s and so named because they were not associated with any known disease. Here, we report a previously unknown reovirus (named “Melaka virus”) isolated from a 39-year-old male patient in Melaka, Malaysia, who was suffering from high fever and acute respiratory disease at the time of virus isolation. Two of his family members developed similar symptoms ≈1 week later and had serological evidence of infection with the same virus. Epidemiological tracing revealed that the family was exposed to a bat in the house ≈1 week before the onset of the father's clinical symptoms. Genome sequence analysis indicated a close genetic relationship between Melaka virus and Pulau virus, a reovirus isolated in 1999 from fruit bats in Tioman Island, Malaysia. Screening of sera collected from human volunteers on the island revealed that 14 of 109 (13%) were positive for both Pulau and Melaka viruses. This is the first report of an orthoreovirus in association with acute human respiratory diseases. Melaka virus is serologically not related to the different types of mammalian reoviruses that were known to infect humans asymptomatically. These data indicate that bat-borne reoviruses can be transmitted to and cause clinical diseases in humans. PMID:17592121

  15. Genetic analysis and antigenic characterization of swine origin influenza viruses isolated from humans in the United States, 1990-2010.

    PubMed

    Shu, Bo; Garten, Rebecca; Emery, Shannon; Balish, Amanda; Cooper, Lynn; Sessions, Wendy; Deyde, Varough; Smith, Catherine; Berman, LaShondra; Klimov, Alexander; Lindstrom, Stephen; Xu, Xiyan

    2012-01-01

    Swine influenza viruses (SIV) have been recognized as important pathogens for pigs and occasional human infections with swine origin influenza viruses (SOIV) have been reported. Between 1990 and 2010, a total of twenty seven human cases of SOIV infections have been identified in the United States. Six viruses isolated from 1990 to 1995 were recognized as classical SOIV (cSOIV) A(H1N1). After 1998, twenty-one SOIV recovered from human cases were characterized as triple reassortant (tr_SOIV) inheriting genes from classical swine, avian and human influenza viruses. Of those twenty-one tr_SOIV, thirteen were of A(H1N1), one of A(H1N2), and seven of A(H3N2) subtype. SOIV characterized were antigenically and genetically closely related to the subtypes of influenza viruses circulating in pigs but distinct from contemporary influenza viruses circulating in humans. The diversity of subtypes and genetic lineages in SOIV cases highlights the importance of continued surveillance at the animal-human interface. PMID:22078166

  16. Earthsickness: circumnavigation and the terrestrial human body, 1520-1800.

    PubMed

    Chaplin, Joyce E

    2012-01-01

    From their distinctive experience of going around the world, maritime circumnavigators concluded that their characteristic disease, sea scurvy, must result from their being away from land too long, much longer than any other sailors. They offered their scorbutic bodies as proof that humans were terrestrial creatures, physically suited to the earthly parts of a terraqueous globe. That arresting claim is at odds with the current literature on the cultural implications of European expansion, which has emphasized early modern colonists' and travelers' fear of alien places, and has concluded that they had a small and restricted geographic imagination that fell short of the planetary consciousness associated with the nineteenth and twentieth centuries. But circumnavigators did conceive of themselves as actors on a planetary scale, as creatures adapted to all of the land on Earth, not just their places of origin. PMID:23263345

  17. Geographic population structure analysis of worldwide human populations infers their biogeographical origins

    PubMed Central

    Elhaik, Eran; Tatarinova, Tatiana; Chebotarev, Dmitri; Piras, Ignazio S.; Maria Calò, Carla; De Montis, Antonella; Atzori, Manuela; Marini, Monica; Tofanelli, Sergio; Francalacci, Paolo; Pagani, Luca; Tyler-Smith, Chris; Xue, Yali; Cucca, Francesco; Schurr, Theodore G.; Gaieski, Jill B.; Melendez, Carlalynne; Vilar, Miguel G.; Owings, Amanda C.; Gómez, Rocío; Fujita, Ricardo; Santos, Fabrício R.; Comas, David; Balanovsky, Oleg; Balanovska, Elena; Zalloua, Pierre; Soodyall, Himla; Pitchappan, Ramasamy; GaneshPrasad, ArunKumar; Hammer, Michael; Matisoo-Smith, Lisa; Wells, R. Spencer; Acosta, Oscar; Adhikarla, Syama; Adler, Christina J.; Bertranpetit, Jaume; Clarke, Andrew C.; Cooper, Alan; Der Sarkissian, Clio S. I.; Haak, Wolfgang; Haber, Marc; Jin, Li; Kaplan, Matthew E.; Li, Hui; Li, Shilin; Martínez-Cruz, Begoña; Merchant, Nirav C.; Mitchell, John R.; Parida, Laxmi; Platt, Daniel E.; Quintana-Murci, Lluis; Renfrew, Colin; Lacerda, Daniela R.; Royyuru, Ajay K.; Sandoval, Jose Raul; Santhakumari, Arun Varatharajan; Soria Hernanz, David F.; Swamikrishnan, Pandikumar; Ziegle, Janet S.

    2014-01-01

    The search for a method that utilizes biological information to predict humans’ place of origin has occupied scientists for millennia. Over the past four decades, scientists have employed genetic data in an effort to achieve this goal but with limited success. While biogeographical algorithms using next-generation sequencing data have achieved an accuracy of 700 km in Europe, they were inaccurate elsewhere. Here we describe the Geographic Population Structure (GPS) algorithm and demonstrate its accuracy with three data sets using 40,000–130,000 SNPs. GPS placed 83% of worldwide individuals in their country of origin. Applied to over 200 Sardinians villagers, GPS placed a quarter of them in their villages and most of the rest within 50 km of their villages. GPS’s accuracy and power to infer the biogeography of worldwide individuals down to their country or, in some cases, village, of origin, underscores the promise of admixture-based methods for biogeography and has ramifications for genetic ancestry testing. PMID:24781250

  18. Understanding human original actions directed at real-world goals: the role of the lateral prefrontal cortex.

    PubMed

    Sitnikova, Tatiana; Rosen, Bruce R; Lord, Louis-David; West, W Caroline

    2014-12-01

    Adaptive, original actions, which can succeed in multiple contextual situations, require understanding of what is relevant to a goal. Recognizing what is relevant may also help in predicting kinematics of observed, original actions. During action observation, comparisons between sensory input and expected action kinematics have been argued critical to accurate goal inference. Experimental studies with laboratory tasks, both in humans and nonhuman primates, demonstrated that the lateral prefrontal cortex (LPFC) can learn, hierarchically organize, and use goal-relevant information. To determine whether this LPFC capacity is generalizable to real-world cognition, we recorded functional magnetic resonance imaging (fMRI) data in the human brain during comprehension of original and usual object-directed actions embedded in video-depictions of real-life behaviors. We hypothesized that LPFC will contribute to forming goal-relevant representations necessary for kinematic predictions of original actions. Additionally, resting-state fMRI was employed to examine functional connectivity between the brain regions delineated in the video fMRI experiment. According to behavioral data, original videos could be understood by identifying elements relevant to real-life goals at different levels of abstraction. Patterns of enhanced activity in four regions in the left LPFC, evoked by original, relative to usual, video scenes, were consistent with previous neuroimaging findings on representing abstract and concrete stimuli dimensions relevant to laboratory goals. In the anterior left LPFC, the activity increased selectively when representations of broad classes of objects and actions, which could achieve the perceived overall behavioral goal, were likely to bias kinematic predictions of original actions. In contrast, in the more posterior regions, the activity increased even when concrete properties of the target object were more likely to bias the kinematic prediction. Functional connectivity was observed between contiguous regions along the rostro-caudal LPFC axis, but not between the regions that were not immediately adjacent. These findings generalize the representational hierarchy account of LPFC function to diverse core principles that can govern both production and comprehension of flexible real-life behavior. PMID:25224997

  19. Understanding Human Original Actions Directed at Real-World Goals: The Role of the Lateral Prefrontal Cortex

    PubMed Central

    Sitnikova, Tatiana; Rosen, Bruce R.; Lord, Louis-David; West, W. Caroline

    2014-01-01

    Adaptive, original actions, which can succeed in multiple contextual situations, require understanding of what is relevant to a goal. Recognizing what is relevant may also help in predicting kinematics of observed, original actions. During action observation, comparisons between sensory input and expected action kinematics have been argued critical to accurate goal inference. Experimental studies with laboratory tasks, both in humans and nonhuman primates, demonstrated that the lateral prefrontal cortex (LPFC) can learn, hierarchically organize, and use goal-relevant information. To determine whether this LPFC capacity is generalizable to real-world cognition, we recorded functional magnetic resonance imaging (fMRI) data in the human brain during comprehension of original and usual object-directed actions embedded in video-depictions of real-life behaviors. We hypothesized that LPFC will contribute to forming goal-relevant representations necessary for kinematic predictions of original actions. Additionally, resting-state fMRI was employed to examine functional connectivity between the brain regions delineated in the video fMRI experiment. According to behavioral data, original videos could be understood by identifying elements relevant to real-life goals at different levels of abstraction. Patterns of enhanced activity in four regions in the left LPFC, evoked by original, relative to usual, video scenes, were consistent with previous neuroimaging findings on representing abstract and concrete stimuli dimensions relevant to laboratory goals. In the anterior left LPFC, the activity increased selectively when representations of broad classes of objects and actions, which could achieve the perceived overall behavioral goal, were likely to bias kinematic predictions of original actions. In contrast, in the more posterior regions, the activity increased even when concrete properties of the target object were more likely to bias the kinematic prediction. Functional connectivity was observed between contiguous regions along the rostro-caudal LPFC axis, but not between the regions that were not immediately adjacent. These findings generalize the representational hierarchy account of LPFC function to diverse core principles that can govern both production and comprehension of flexible real-life behavior. PMID:25224997

  20. Embryo Form Project: An original technique for the three-dimensional reconstruction of human embryo morphology.

    PubMed

    Labrousse, M; Micard, E; Tonnelet, R; Cendre, R; Delmas, V; Naidich, T; Braun, M

    2015-12-01

    Our current knowledge on the developmental stages of human embryogenesis has derived from limited numbers of classical studies. Computer technology now permits accurate 3D reconstruction of embryo morphology from serial histological sections. We present a successful technique that uses either fresh or preserved serial histological sections to generate highly detailed 3D image reconstructions of very small human embryos. We present the data we obtained from the reconstruction in virtual space of previously sectioned 15 and 22.5mm embryos. Their morphologies were studied using a DICOM viewer which permitted the analysis of any specific structure in any required orientation. To our knowledge, this is the first time human embryos have been reconstructed in this way. We believe that this reconstruction technique could improve our knowledge on embryo morphogenesis, especially if coupled to the study of genes involved in embryonic development. It may also prove to be a useful pedagogical tool. PMID:26219247

  1. An enhanced role and expanded developmental origins for gamma-aminobutyric acidergic interneurons in the human cerebral cortex.

    PubMed

    Clowry, Gavin J

    2015-10-01

    Human beings have considerably expanded cognitive abilities compared with all other species and they also have a relatively larger cerebral cortex compared with their body size. But is a bigger brain the only reason for higher cognition or have other features evolved in parallel? Humans have more and different types of GABAergic interneurons, found in different places, than our model species. Studies are beginning to show differences in function. Is this expanded repertoire of functional types matched by an evolution of their developmental origins? Recent studies support the idea that generation of interneurons in the ventral telencephalon may be more complicated in primates, which have evolved a large and complex outer subventricular zone in the ganglionic eminences. In addition, proportionally more interneurons appear to be produced in the caudal ganglionic eminence, the majority of which populate the superficial layers of the cortex. Whether or not the cortical proliferative zones are a source of interneurogenesis, and to what extent and of what significance, is a contentious issue. As there is growing evidence that conditions such as autism, schizophrenia and congenital epilepsy may have developmental origins in the failure of interneuron production and migration, it is important we understand fully the similarities and differences between human development and our animal models. PMID:24839870

  2. Novel avian-origin human influenza A(H7N9) can be transmitted between ferrets via respiratory droplets.

    PubMed

    Xu, Lili; Bao, Linlin; Deng, Wei; Dong, Libo; Zhu, Hua; Chen, Ting; Lv, Qi; Li, Fengdi; Yuan, Jing; Xiang, Zhiguang; Gao, Kai; Xu, Yanfeng; Huang, Lan; Li, Yanhong; Liu, Jiangning; Yao, Yanfeng; Yu, Pin; Li, Xiyan; Huang, Weijuan; Zhao, Xiang; Lan, Yu; Guo, Junfeng; Yong, Weidong; Wei, Qiang; Chen, Honglin; Zhang, Lianfeng; Qin, Chuan

    2014-02-15

    The outbreak of human infections caused by novel avian-origin influenza A(H7N9) in China since March 2013 underscores the need to better understand the pathogenicity and transmissibility of these viruses in mammals. In a ferret model, the pathogenicity of influenza A(H7N9) was found to be less than that of an influenza A(H5N1) strain but comparable to that of 2009 pandemic influenza A(H1N1), based on the clinical signs, mortality, virus dissemination, and results of histopathologic analyses. Influenza A(H7N9) could replicate in the upper and lower respiratory tract, the heart, the liver, and the olfactory bulb. It is worth noting that influenza A(H7N9) exhibited a low level of transmission between ferrets via respiratory droplets. There were 4 mutations in the virus isolated from the contact ferret: D678Y in the gene encoding PB2, R157K in the gene encoding hemagglutinin (H3 numbering), I109T in the gene encoding nucleoprotein, and T10I in the gene encoding neuraminidase. These data emphasized that avian-origin influenza A(H7N9) can be transmitted between mammals, highlighting its potential for human-to-human transmissibility. PMID:23990570

  3. Replicon typing of plasmids carrying blaCTX-M-1 in Enterobacteriaceae of animal, environmental and human origin

    PubMed Central

    Zurfluh, Katrin; Jakobi, Gianna; Stephan, Roger; Hächler, Herbert; Nüesch-Inderbinen, Magdalena

    2014-01-01

    Objectives: The aim of this work was to determine the plasmid replicon profiles of a collection of blaCTX-M-1-positive enterobacterial strains. The isolates originated from chicken in the production pyramid, healthy food-producing animals at slaughter (chicken, calves, and pigs), chicken retail meat, environmental isolates originating from water bodies, and isolates from humans. A selection of IncI and IncN plasmids were characterized by multilocus sequence typing in order to determine their epidemiological relatedness. Methods: Transconjugants of 74 blaCTX-M-1-positive isolates were analyzed by PCR-based replicon typing and by PCR-based plasmid multilocus sequence typing. Results: The incompatibility groups detected among the blaCTX-M-1-harboring plasmids included IncI1, IncN, IncHI1B, IncF, IncFIIS, IncFIB, and IncB/O, with plasmid lineage IncI1/ST3 predominating in isolates from chicken and from humans. Lineage IncN/ST1 was detected mainly in isolates from pigs. For the first time, blaCTX-M-1 genes encoded on IncHI1 plasmids were detected in isolates from cattle and from water bodies. Conclusions: This study identifies plasmid lineages that are contributing to the dissemination of blaCTX-M-1 genes in the food chain, the environment, and humans. PMID:25400623

  4. Diverse Genetic Markers Concordantly Identify Bovine Origin Escherichia coli O157 Genotypes Underrepresented in Human Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic markers previously reported to occur at significantly different frequencies in isolates of Escherichia coli O157:H7 obtained from cattle and from clinically affected humans are congruent and delineate at least five groups. Isolates in three of these groups consistently carry one or more mark...

  5. Porcine-Origin Gentamicin-Resistant Enterococcus faecalis in Humans, Denmark

    PubMed Central

    Schønheyder, Henrik C.; Lester, Camilla H.; Olsen, Stefan S.; Porsbo, Lone J.; Garcia-Migura, Lourdes; Jensen, Lars B.; Bisgaard, Magne; Hammerum, Anette M.

    2010-01-01

    During 2001–2002, high-level gentamicin-resistant (HLGR) Enterococcus faecalis isolates were detected in 2 patients in Denmark who had infective endocarditis and in pigs and pork. Our results demonstrate that these isolates belong to the same clonal group, which suggests that pigs are a source of HLGR E. faecalis infection in humans. PMID:20350387

  6. Genetic absolute dating based on microsatellites and the origin of modern humans.

    PubMed Central

    Goldstein, D B; Ruiz Linares, A; Cavalli-Sforza, L L; Feldman, M W

    1995-01-01

    We introduce a new genetic distance for microsatellite loci, incorporating features of the stepwise mutation model, and test its performance on microsatellite polymorphisms in humans, chimpanzees, and gorillas. We find that it performs well in determining the relations among the primates, but less well than other distance measures (not based on the stepwise mutation model) in determining the relations among closely related human populations. However, the deepest split in the human phylogeny seems to be accurately reconstructed by the new distance and separates African and non-African populations. The new distance is independent of population size and therefore allows direct estimation of divergence times if the mutation rate is known. Based on 30 microsatellite polymorphisms and a recently reported average mutation rate of 5.6 x 10(-4) at 15 dinucleotide microsatellites, we estimate that the deepest split in the human phylogeny occurred about 156,000 years ago. Unlike most previous estimates, ours requires no external calibration of the rate of molecular evolution. We can use such calibrations, however, to test our estimate. PMID:7624310

  7. Production of orally applicable new drug or drug combinations from natural origin capsaicinoids for human medical therapy.

    PubMed

    Mózsik, Gyula; Past, Tibor; Dömötör, András; Kuzma, Mónika; Perjési, Pál

    2010-01-01

    It is well known that the capsaicin stimulates (in small doses) or impairs (in high doses) the capsaicin-sensitive afferent nerves and the final effects of capsaicin depend on its applied doses. The effects of capsaicin were analyzed on the gastrointestinal mucosal protection and injury in animal experiments and in human beings (from 1980 up to now). From 2005 to 2008 an interdisciplinary group (21 researchers) participated in the production of orally applicable drug or drug combinations from capsaicin for human medical therapy of patients suffering from cardiovascular, degenerative joint and locomotor diseases, who received in their treatments non-steroidal anti-inflammatory compounds (NSAIDs). Our studies were based on the results of the NSAIDs-induced gastrointestinal side effects could be detected by application of small doses of capsaicin. Because natural (plant origin) capsaicin is chemically does not represent a uniform entity and used in the international research, consequently the authors met a lot of unpredictable scientific problems during the time of production of new capsaicin containing (alone or in combinations) drug before receiving official permissions from the different national and international authorities to start the classical human clinical pharmacological studies. This paper summarizes the different steps from the basic physiological and pharmacological notes (in animals), plant cultivation, chemistry of substance(s), animal (general and germinative) acute and chronic toxicology, human actions, basic clinical pharmacology of natural capsaicin (capsaicinoids) to introduce and to develop a new drug (or drug combinations) in the human medical therapy. PMID:20166996

  8. Genetic origin, admixture, and asymmetry in maternal and paternal human lineages in Cuba

    PubMed Central

    2008-01-01

    Background Before the arrival of Europeans to Cuba, the island was inhabited by two Native American groups, the Tainos and the Ciboneys. Most of the present archaeological, linguistic and ancient DNA evidence indicates a South American origin for these populations. In colonial times, Cuban Native American people were replaced by European settlers and slaves from Africa. It is still unknown however, to what extent their genetic pool intermingled with and was 'diluted' by the arrival of newcomers. In order to investigate the demographic processes that gave rise to the current Cuban population, we analyzed the hypervariable region I (HVS-I) and five single nucleotide polymorphisms (SNPs) in the mitochondrial DNA (mtDNA) coding region in 245 individuals, and 40 Y-chromosome SNPs in 132 male individuals. Results The Native American contribution to present-day Cubans accounted for 33% of the maternal lineages, whereas Africa and Eurasia contributed 45% and 22% of the lineages, respectively. This Native American substrate in Cuba cannot be traced back to a single origin within the American continent, as previously suggested by ancient DNA analyses. Strikingly, no Native American lineages were found for the Y-chromosome, for which the Eurasian and African contributions were around 80% and 20%, respectively. Conclusion While the ancestral Native American substrate is still appreciable in the maternal lineages, the extensive process of population admixture in Cuba has left no trace of the paternal Native American lineages, mirroring the strong sexual bias in the admixture processes taking place during colonial times. PMID:18644108

  9. The Origin of Human Milk Bacteria: Is There a Bacterial Entero-Mammary Pathway during Late Pregnancy and Lactation?1234

    PubMed Central

    Rodrguez, Juan M.

    2014-01-01

    Human milk is a source of bacteria to the infant gut; however, the origin of milk bacteria, as well as their impact on neonatal gut microbiota establishment, remains largely unknown. In the past years, results provided by different research groups suggest that certain bacteria from the maternal gastrointestinal tract could translocate through a mechanism involving mononuclear immune cells, migrate to the mammary glands via an endogenous cellular route (the bacterial entero-mammary pathway), and subsequently colonize the gastrointestinal tract of the breast-fed neonate. If such findings are confirmed in the future, we could exert a positive influence on infant health by modulating the maternal gut microbiota. PMID:25398740

  10. What Is the Origin of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Clonal Complex 398 Isolates from Humans without Livestock Contact? An Epidemiological and Genetic Analysis

    PubMed Central

    van Wamel, W. J. B.; Snijders, S. V.; Willems, R. J.; van Duijkeren, E.; Broens, E. M.; Wagenaar, J. A.; Lindsay, J. A.; Vos, M. C.

    2015-01-01

    Fifteen percent of all methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) human carriers detected in The Netherlands had not been in direct contact with pigs or veal calves. To ensure low MRSA prevalence, it is important to investigate the likely origin of this MRSA of unknown origin (MUO). Recently, it was shown that CC398 strains originating from humans and animals differ in the presence of specific mobile genetic elements (MGEs). We hypothesized that determining these specific MGEs in MUO isolates and comparing them with a set of CC398 isolates of various known origin might provide clues to their origin. MUO CC398 isolates were compared to MRSA CC398 isolates obtained from humans with known risk factors, a MRSA CC398 outbreak isolate, livestock associated (LA) MRSA CC398 isolates from pigs, horses, chickens, and veal calves, and five methicillin-susceptible Staphylococcus aureus (MSSA) CC398 isolates of known human origin. All strains were spa typed, and the presence or absence of, scn, chp, φ3 int, φ6 int, φ7 int, rep7, rep27, and cadDX was determined by PCRs. The MRSA CC398 in humans, MUO, or MRSA of known origin (MKO) resembled MRSA CC398 as found in pigs and not MSSA CC398 as found in humans. The distinct human MSSA CC398 spa type, t571, was not present among our MRSA CC398 strains; MRSA CC398 was tetracycline resistant and carried no φ3 bacteriophage with scn and chp. We showed by simple PCR means that human MUO CC398 carriers carried MRSA from livestock origin, suggestive of indirect transmission. Although the exact transmission route remains unknown, direct human-to-human transmission remains a possibility as well. PMID:25809975

  11. What Is the Origin of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Clonal Complex 398 Isolates from Humans without Livestock Contact? An Epidemiological and Genetic Analysis.

    PubMed

    Lekkerkerk, W S N; van Wamel, W J B; Snijders, S V; Willems, R J; van Duijkeren, E; Broens, E M; Wagenaar, J A; Lindsay, J A; Vos, M C

    2015-06-01

    Fifteen percent of all methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) human carriers detected in The Netherlands had not been in direct contact with pigs or veal calves. To ensure low MRSA prevalence, it is important to investigate the likely origin of this MRSA of unknown origin (MUO). Recently, it was shown that CC398 strains originating from humans and animals differ in the presence of specific mobile genetic elements (MGEs). We hypothesized that determining these specific MGEs in MUO isolates and comparing them with a set of CC398 isolates of various known origin might provide clues to their origin. MUO CC398 isolates were compared to MRSA CC398 isolates obtained from humans with known risk factors, a MRSA CC398 outbreak isolate, livestock associated (LA) MRSA CC398 isolates from pigs, horses, chickens, and veal calves, and five methicillin-susceptible Staphylococcus aureus (MSSA) CC398 isolates of known human origin. All strains were spa typed, and the presence or absence of, scn, chp, φ3 int, φ6 int, φ7 int, rep7, rep27, and cadDX was determined by PCRs. The MRSA CC398 in humans, MUO, or MRSA of known origin (MKO) resembled MRSA CC398 as found in pigs and not MSSA CC398 as found in humans. The distinct human MSSA CC398 spa type, t571, was not present among our MRSA CC398 strains; MRSA CC398 was tetracycline resistant and carried no φ3 bacteriophage with scn and chp. We showed by simple PCR means that human MUO CC398 carriers carried MRSA from livestock origin, suggestive of indirect transmission. Although the exact transmission route remains unknown, direct human-to-human transmission remains a possibility as well. PMID:25809975

  12. Population genomics reveals the origin and asexual evolution of human infective trypanosomes.

    PubMed

    Weir, William; Capewell, Paul; Foth, Bernardo; Clucas, Caroline; Pountain, Andrew; Steketee, Pieter; Veitch, Nicola; Koffi, Mathurin; De Meeûs, Thierry; Kaboré, Jacques; Camara, Mamadou; Cooper, Anneli; Tait, Andy; Jamonneau, Vincent; Bucheton, Bruno; Berriman, Matt; MacLeod, Annette

    2016-01-01

    Evolutionary theory predicts that the lack of recombination and chromosomal re-assortment in strictly asexual organisms results in homologous chromosomes irreversibly accumulating mutations and thus evolving independently of each other, a phenomenon termed the Meselson effect. We apply a population genomics approach to examine this effect in an important human pathogen, Trypanosoma brucei gambiense. We determine that T.b. gambiense is evolving strictly asexually and is derived from a single progenitor, which emerged within the last 10,000 years. We demonstrate the Meselson effect for the first time at the genome-wide level in any organism and show large regions of loss of heterozygosity, which we hypothesise to be a short-term compensatory mechanism for counteracting deleterious mutations. Our study sheds new light on the genomic and evolutionary consequences of strict asexuality, which this pathogen uses as it exploits a new biological niche, the human population. PMID:26809473

  13. In vitro selection criteria for probiotic bacteria of human origin: correlation with in vivo findings.

    PubMed

    Dunne, C; O'Mahony, L; Murphy, L; Thornton, G; Morrissey, D; O'Halloran, S; Feeney, M; Flynn, S; Fitzgerald, G; Daly, C; Kiely, B; O'Sullivan, G C; Shanahan, F; Collins, J K

    2001-02-01

    The enteric flora comprises approximately 95% of the total number of cells in the human body and can elicit immune responses while protecting against microbial pathogens. However, the resident bacterial flora of the gastrointestinal tract may also be implicated in the pathogenesis of diseases such as inflammatory bowel disease (ulcerative colitis and Crohn disease). The objectives of the Probiotic Research Group based at University College Cork were to isolate and identify lactic acid bacteria exhibiting beneficial probiotic traits, such as bile tolerance in the absence of deconjugation activity, acid resistance, adherence to host epithelial tissue, and in vitro antagonism of pathogenic microorganisms or those suspected of promoting inflammation. To isolate potentially effective probiotic bacteria, we screened the microbial population adhering to surgically resected segments of the gastrointestinal tract (the environment in which they may subsequently be reintroduced and required to function). In total, 1500 bacterial strains from resected human terminal ilea were assessed. From among these organisms, Lactobacillus salivarius subsp. salivarius strain UCC118 was selected for further study. In mouse feeding trials, milk-borne L. salivarius strain UCC118 could successfully colonize the murine gastrointestinal tract. A human feeding study conducted in 80 healthy volunteers showed that yogurt can be used as a vehicle for delivery of strain UCC118 to the human gastrointestinal tract with considerable efficacy in influencing gut flora and colonization. In summary, we developed criteria for in vitro selection of probiotic bacteria that may reflect certain in vivo effects on the host such as modulation of gastrointestinal tract microflora. PMID:11157346

  14. Human motor unit recordings: origins and insight into the integrated motor system.

    PubMed

    Duchateau, Jacques; Enoka, Roger M

    2011-08-29

    Soon after Edward Liddell [1895-1981] and Charles Sherrington [1857-1952] introduced the concept of a motor unit in 1925 and the necessary technology was developed, the recording of single motor unit activity became feasible in humans. It was quickly discovered by Edgar Adrian [1889-1977] and Detlev Bronk [1897-1975] that the force exerted by muscle during voluntary contractions was the result of the concurrent recruitment of motor units and modulation of the rate at which they discharged action potentials. Subsequent studies found that the relation between discharge frequency and motor unit force was characterized by a sigmoidal function. Based on observations on experimental animals, Elwood Henneman [1915-1996] proposed a "size principle" in 1957 and most studies in humans focussed on validating this concept during various types of muscle contractions. By the end of the 20th C, the experimental evidence indicated that the recruitment order of human motor units was determined primarily by motoneuron size and that the occasional changes in recruitment order were not an intended strategy of the central nervous system. Fundamental knowledge on the function of Sherrington's "common final pathway" was expanded with observations on motor unit rotation, minimal and maximal discharge rates, discharge variability, and self-sustained firing. Despite the great amount of work on characterizing motor unit activity during the first century of inquiry, however, many basic questions remain unanswered and these limit the extent to which findings on humans and experimental animals can be integrated and generalized to all movements. PMID:21762884

  15. The origin of human chromosome 2 analyzed by comparative chromosome mapping with a DNA microlibrary.

    PubMed

    Wienberg, J; Jauch, A; Lüdecke, H J; Senger, G; Horsthemke, B; Claussen, U; Cremer, T; Arnold, N; Lengauer, C

    1994-09-01

    Fluorescence in situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescence in situ hybridization and comparative mapping of the chromosomes of human, great apes (Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus) and Old World monkeys (Macaca fuscata and Cercopithecus aethiops). Inversions were found in the pericentric region of the primate chromosome 2p homologs in great apes, and the hybridization pattern demonstrates the known phylogenetically derived telomere fusion in the line that leads to human chromosome 2. The hybridization of the 2q microlibrary to chromosomes of Old World monkeys gave a different pattern from that in the gorilla and the orang-utan, but a pattern similar to that of chimpanzees. This suggests convergence of chromosomal rearrangements in different phylogenetic lines. PMID:7981945

  16. Electrostatic origin of in vitro aggregation of human γ-crystallin.

    PubMed

    Mohr, Benjamin G; Dobson, Cassidy M; Garman, Scott C; Muthukumar, Murugappan

    2013-09-28

    The proteins α-, β-, and γ-crystallins are the major components of the lens in the human eye. Using dynamic light scattering method, we have performed in vitro investigations of protein-protein interactions in dilute solutions of human γ-crystallin and α-crystallin. We find that γ-crystallin spontaneously aggregates into finite-sized clusters in phosphate buffer solutions. There are two distinct populations of unaggregated and aggregated γ-crystallins in these solutions. On the other hand, α-crystallin molecules are not aggregated into large clusters in solutions of α-crystallin alone. When α-crystallin and γ-crystallin are mixed in phosphate buffer solutions, we demonstrate that the clusters of γ-crystallin are prevented. By further investigating the roles of temperature, protein concentration, pH, salt concentration, and a reducing agent, we show that the aggregation of γ-crystallin under our in vitro conditions arises from non-covalent electrostatic interactions. In addition, we show that aggregation of γ-crystallin occurs under the dilute in vitro conditions even in the absence of oxidizing agents that can induce disulfide cross-links, long considered to be responsible for human cataracts. Aggregation of γ-crystallin when maintained under reducing conditions suggests that oxidation does not contribute to the aggregation in dilute solutions. PMID:24089726

  17. Campylobacter jejuni strains of human and chicken origin are invasive in chickens after oral challenge.

    PubMed

    Knudsen, Katrine Nørrelund; Bang, Dang Duong; Andresen, Lars Ole; Madsen, Mogens

    2006-03-01

    The aim of the study was to evaluate the colonizing ability and the invasive capacity of selected Campylobacter jejuni strains of importance for the epidemiology of C jejuni in Danish broiler chickens. Four C. jejuni strains were selected for experimental colonization studies in day-old and 14-day-old chickens hatched from specific pathogen free (SPF) eggs. Of the four C. jejuni strains tested, three were Penner heat-stable serotype 2, flaA type 1/1, the most common type found among broilers and human cases in Denmark. The fourth strain was Penner heat-stable serotype 19, which has been shown to be associated with the Guillain Barré Syndrome (GBS) in humans. The minimum dose for establishing colonization in the day-old chickens was approximately 2 cfu, whereas two- to threefold higher doses were required for establishing colonization in the 14-day-old chickens. Two of the C. jejuni strains were shown to be invasive in orally challenged chickens as well as in three different human epithelial cell lines. PMID:16617974

  18. Unraveling the origin of exponential law in intra-urban human mobility

    PubMed Central

    Liang, Xiao; Zhao, Jichang; Dong, Li; Xu, Ke

    2013-01-01

    The vast majority of travel takes place within cities. Recently, new data has become available which allows for the discovery of urban mobility patterns which differ from established results about long distance travel. Specifically, the latest evidence increasingly points to exponential trip length distributions, contrary to the scaling laws observed on larger scales. In this paper, in order to explore the origin of the exponential law, we propose a new model which can predict individual flows in urban areas better. Based on the model, we explain the exponential law of intra-urban mobility as a result of the exponential decrease in average population density in urban areas. Indeed, both empirical and analytical results indicate that the trip length and the population density share the same exponential decaying rate. PMID:24136012

  19. Human brucellosis among pyrexia of unknown origin cases and occupationally exposed individuals in Goa Region, India

    PubMed Central

    Pathak, Ajay D.; Dubal, Zunjar B.; Doijad, Swapnil; Raorane, Abhay; Rodrigues, Savio; Naik, Rajeshwar; Naik-Gaonkar, Shraddha; Kalorey, Dewanand R.; Kurkure, Nitin V.; Naik, Rajesh; Barbuddhe, Sukhadeo B.

    2014-01-01

    Background Brucellosis is a widespread zoonotic infection. This disease is endemic in many parts of Asia, including India. Brucellosis is a major cause of pyrexia of unknown origin (PUO). Persons exposed to infected animals or contaminated animal products are at high risk. Seropositivity among animal handlers, veterinarians and dairy workers has been documented in India. Thus, the present study was aimed to determine prevalence of brucellosis among PUO cases and occupationally exposed individuals. Methods In this study, serum samples (n=282) from cases of pyrexia of unknown origin (PUO) (n=243), and occupationally exposed individuals (n=39) were collected and tested for brucellosis by Rose Bengal plate test (RBPT), serum agglutination test (SAT), indirect ELISA, IgG and IgM ELISA. Blood culture for isolation of Brucella was performed for 10 serologically positive patients using BACTEC 9050 automated blood culture system. Biochemical tests and PCR techniques were used for confirmation of the isolates. Results Of the samples tested, 4.25%, 3.54%, 6.02% and 4.96% samples were positive by RBPT, SAT, indirect ELISA and IgG ELISA, respectively. None of the sample was positive for IgM ELISA. Of the 10 blood samples cultured bacteriologically, one Brucella isolate was recovered. The isolate was confirmed as Brucella abortus. Amplification of the bcsp31 and IS711 genes was also observed. Conclusion Seropositivity for brucellosis was observed among PUO cases, animal handlers and dairy workers in Goa, India. The serological tests showed variable results. One Brucella isolate was obtained by performing blood culture. Confirmation of the case was done rapidly using molecular tools. General awareness about clinical symptoms should be increased which will improve proper diagnosis within short time frame. PMID:24762925

  20. Phylogenetic evolution of swine-origin human influenza virus: a pandemic H1N1 2009.

    PubMed

    Kowalczyk, A; Markowska-Daniel, I

    2010-01-01

    The knowledge of the genome constellation in pandemic influenza A virus H1N1 2009 from different countries and different hosts is valuable for monitoring and understanding of the evolution and migration of these strains. The complete genome sequences of selected worldwide distributed influenza A viruses are publicly available and there have been few longitudinal genome studies of human, avian and swine influenza A viruses. All possible to download SIV sequences of influenza A viruses available at GISAID Platform (Global Initiative on Sharing Avian Influenza Data) were analyzed firstly through the web servers of the Influenza Virus Resource in NCBI. Phylogenetic study of circulating human pandemic H1N1 virus indicated that the new variant possesses a distinctive evolutionary trait. There is no one way the pandemic H1N1 have acquired new genes from other distinguishable viruses circulating recently in local human, pig or domestic poultry populations from various geographic regions. The extensive genetic diversity among whole segments present in pandemic H1N1 genome suggests that multiple introduction of virus have taken place during the period 1999-2009. The initial interspecies transmission could have occurred in the long-range past and after it the reassortants steps lead to three lineages: classical SIV prevalent in the North America, avian-like SIV in Europe and avian-like related SIV in Asia. This analysis contributes to the evidence that pigs are not the only hosts playing the role of "mixing vessel", as it was suggested for many years. PMID:21033564

  1. Origin and propagation of human gastric slow-wave activity defined by high-resolution mapping.

    PubMed

    O'Grady, Gregory; Du, Peng; Cheng, Leo K; Egbuji, John U; Lammers, Wim J E P; Windsor, John A; Pullan, Andrew J

    2010-09-01

    Slow waves coordinate gastric motility, and abnormal slow-wave activity is thought to contribute to motility disorders. The current understanding of normal human gastric slow-wave activity is based on extrapolation from data derived from sparse electrode recordings and is therefore potentially incomplete. This study employed high-resolution (HR) mapping to reevaluate human gastric slow-wave activity. HR mapping was performed in 12 patients with normal stomachs undergoing upper abdominal surgery, using flexible printed circuit board (PCB) arrays (interelectrode distance 7.6 mm). Up to six PCBs (192 electrodes; 93 cm(2)) were used simultaneously. Slow-wave activity was characterized by spatiotemporal mapping, and regional frequencies, amplitudes, and velocities were defined and compared. Slow-wave activity in the pacemaker region (mid to upper corpus, greater curvature) was of greater amplitude (mean 0.57 mV) and higher velocity (8.0 mm/s) than the corpus (0.25 mV, 3.0 mm/s) (P < 0.001) and displayed isotropic propagation. A marked transition to higher amplitude and velocity activity occurred in the antrum (0.52 mV, 5.9 mm/s) (P < 0.001). Multiple (3-4) wavefronts were found to propagate simultaneously in the organoaxial direction. Frequencies were consistent between regions (2.83 +/- 0.35 cycles per min). HR mapping has provided a more complete understanding of normal human gastric slow-wave activity. The pacemaker region is associated with high-amplitude, high-velocity activity, and multiple wavefronts propagate simultaneously. These data provide a baseline for future HR mapping studies in disease states and will inform noninvasive diagnostic strategies. PMID:20595620

  2. Serial Propagation of the Microsporidian Enterocytozoon bieneusi of Human Origin in Immunocompromised Rodents

    PubMed Central

    Feng, Xiaochuan; Akiyoshi, Donna E.; Sheoran, Abhineet; Singh, Inderpal; Hanawalt, Joel; Zhang, Quanshun; Widmer, Giovanni; Tzipori, Saul

    2006-01-01

    Enterocytozoon bieneusi, a microsporidian, is clinically one of the most significant opportunistic causes of diarrhea and wasting associated with profound human immunodeficiencies. The lack of an animal model for E. bieneusi hinders serious investigations and limits the availability of spores to individuals with severe human immunodeficiency virus/AIDS disease who are infected with E. bieneusi. The development of procedures for purification and concentration of spores from stools of infected humans has led to the production of immune reagents and provided a source of spores to conduct research, including attempts to develop and serially propagate E. bieneusi in rodent models. We have evaluated and successfully infected six different immunodeficient and/or immunosuppressed rodent models and have demonstrated persistent infections lasting at least 18 weeks in SCID mice and in nude rats. To enhance the intensity and duration of infection in these two models, animals were given anti-gamma interferon monoclonal antibody injections at regular intervals. Of the six models evaluated, nude rats and gerbils immunosuppressed with dexamethasone excreted the highest number of spores and for longer time periods. Four different E. bieneusi isolates were equally infectious, and one of them was serially propagated in nude rats six times over a period of 10 months. Typically, rats challenged orally with 104 spores yielded 2 × 107 to 6.3 × 107 spores per single fecal sample when the level of spores was measured 2 weeks later. Rodent models and a nonhuman source of fresh spores will considerably enhance future investigations on this important opportunistic pathogen, including the screening and evaluation of urgently needed chemotherapeutic agents. PMID:16861628

  3. The origins of polarimetric image contrast between healthy and cancerous human colon tissue

    NASA Astrophysics Data System (ADS)

    Novikova, T.; Pierangelo, A.; Manhas, S.; Benali, A.; Validire, P.; Gayet, B.; De Martino, A.

    2013-06-01

    Experimentally measured spectral Mueller matrix images of ex vivo human colon tissue revealed the contrast enhancement between healthy and cancerous zones of colon specimen compared to unpolarized intensity images. Cancer development starts with abnormal changes which being not yet visible macroscopically may alter the polarization of reflected light. We have shown with experiments and modeling that light scattering by small (sub wavelength) scatterers and light absorption (mainly due to blood hemoglobin) are the key factors for observed polarimetric image contrast. These findings can pave the way for the alternative optical technique for the monitoring and early detection of cancer.

  4. Quantification of Human and Animal Viruses to Differentiate the Origin of the Fecal Contamination Present in Environmental Samples

    PubMed Central

    Bofill-Mas, Sílvia; Rusiñol, Marta; Fernandez-Cassi, Xavier; Carratalà, Anna; Hundesa, Ayalkibet

    2013-01-01

    Many different viruses are excreted by humans and animals and are frequently detected in fecal contaminated waters causing public health concerns. Classical bacterial indicator such as E. coli and enterococci could fail to predict the risk for waterborne pathogens such as viruses. Moreover, the presence and levels of bacterial indicators do not always correlate with the presence and concentration of viruses, especially when these indicators are present in low concentrations. Our research group has proposed new viral indicators and methodologies for determining the presence of fecal pollution in environmental samples as well as for tracing the origin of this fecal contamination (microbial source tracking). In this paper, we examine to what extent have these indicators been applied by the scientific community. Recently, quantitative assays for quantification of poultry and ovine viruses have also been described. Overall, quantification by qPCR of human adenoviruses and human polyomavirus JC, porcine adenoviruses, bovine polyomaviruses, chicken/turkey parvoviruses, and ovine polyomaviruses is suggested as a toolbox for the identification of human, porcine, bovine, poultry, and ovine fecal pollution in environmental samples. PMID:23762826

  5. Defined Conditions for the Isolation and Expansion of Basal Prostate Progenitor Cells of Mouse and Human Origin

    PubMed Central

    Höfner, Thomas; Eisen, Christian; Klein, Corinna; Rigo-Watermeier, Teresa; Goeppinger, Stephan M.; Jauch, Anna; Schoell, Brigitte; Vogel, Vanessa; Noll, Elisa; Weichert, Wilko; Baccelli, Irène; Schillert, Anja; Wagner, Steve; Pahernik, Sascha; Sprick, Martin R.; Trumpp, Andreas

    2015-01-01

    Summary Methods to isolate and culture primary prostate epithelial stem/progenitor cells (PESCs) have proven difficult and ineffective. Here, we present a method to grow and expand both murine and human basal PESCs long term in serum- and feeder-free conditions. The method enriches for adherent mouse basal PESCs with a Lin−SCA-1+CD49f+TROP2high phenotype. Progesterone and sodium selenite are additionally required for the growth of human Lin−CD49f+TROP2high PESCs. The gene-expression profiles of expanded basal PESCs show similarities to ESCs, and NF-kB function is critical for epithelial differentiation of sphere-cultured PESCs. When transplanted in combination with urogenital sinus mesenchyme, expanded mouse and human PESCs generate ectopic prostatic tubules, demonstrating their stem cell activity in vivo. This novel method will facilitate the molecular, genomic, and functional characterization of normal and pathologic prostate glands of mouse and human origin. PMID:25702639

  6. An ancestry informative marker set for determining continental origin: validation and extension using human genome diversity panels

    PubMed Central

    Nassir, Rami; Kosoy, Roman; Tian, Chao; White, Phoebe A; Butler, Lesley M; Silva, Gabriel; Kittles, Rick; Alarcon-Riquelme, Marta E; Gregersen, Peter K; Belmont, John W; De La Vega, Francisco M; Seldin, Michael F

    2009-01-01

    Background Case-control genetic studies of complex human diseases can be confounded by population stratification. This issue can be addressed using panels of ancestry informative markers (AIMs) that can provide substantial population substructure information. Previously, we described a panel of 128 SNP AIMs that were designed as a tool for ascertaining the origins of subjects from Europe, Sub-Saharan Africa, Americas, and East Asia. Results In this study, genotypes from Human Genome Diversity Panel populations were used to further evaluate a 93 SNP AIM panel, a subset of the 128 AIMS set, for distinguishing continental origins. Using both model-based and relatively model-independent methods, we here confirm the ability of this AIM set to distinguish diverse population groups that were not previously evaluated. This study included multiple population groups from Oceana, South Asia, East Asia, Sub-Saharan Africa, North and South America, and Europe. In addition, the 93 AIM set provides population substructure information that can, for example, distinguish Arab and Ashkenazi from Northern European population groups and Pygmy from other Sub-Saharan African population groups. Conclusion These data provide additional support for using the 93 AIM set to efficiently identify continental subject groups for genetic studies, to identify study population outliers, and to control for admixture in association studies. PMID:19630973

  7. Generation of induced pluripotent stem cells from human mesenchymal stem cells of parotid gland origin

    PubMed Central

    Yan, Xing; Xu, Nuo; Meng, Cen; Wang, Bianhong; Yuan, Jinghong; Wang, Caiyun; Li, Yang

    2016-01-01

    The technology to reprogram human somatic cells to pluripotent state allows the generation of patient-specific induced pluripotent stem cells (iPSCs) and holds a great promise for regenerative medicine and autologous transplantation. Here we, for the first time, identified mesenchymal stem cells isolated from parotid gland (hPMSCs) as a suitable candidate for iPSC production. In the present study, hPMSCs were isolated from parotid gland specimens in patients with squamous cell carcinoma of the oral cavity. The mesenchymal stem cell properties of cultured hPMSCs were confirmed by expression of surface markers and induced differentiation into osteogenic, chondrogenic and adipogenic cell lineages. hPMSCs were then reprogrammed to pluripotent cells by episomal vector-mediated transduction of reprogramming factors (OCT3/4, SOX2, KLF4, c-MYC, LIN28 and TP53 shRNA). The resulting hPMSC-iPSCs showed similar characteristics as human embryonic stem cells (ESCs) with regard to morphology, pluripotent markers, global gene expression, and methylation status of pluripotent cell-specific genes OCT4 and NANOG. These hPMSC-iPSCs were able to differentiate into cells of all three germ layers both in vitro and in vivo. Our results indicate that hPMSCs could be an alternative cell source for generation of iPSCs and have the potential to be used in cell-based regenerative medicine. PMID:27158336

  8. Recently recovered Kenyapithecus mandible and its implications for great ape and human origins.

    PubMed Central

    McCrossin, M L; Benefit, B R

    1993-01-01

    We report here a Kenyapithecus africanus juvenile mandible recovered from middle Miocene (ca. 14-16 million years) deposits of Maboko Island (Lake Victoria), Kenya. Symphyseal and dental attributes of the mandible distinguish K. africanus, a species widely regarded as the earliest known member of the great ape and human clade, from other Miocene large-bodied hominoids. The Maboko Island mandible exhibits a markedly proclined symphyseal axis, massive inferior transverse torus, mesiodistally narrow, high-crowned, and strongly procumbent lateral incisor, and molars with cingula restricted to the median buccal cleft. Although the presence of some of these conditions in Kenyapithecus was suggested earlier, the fragmentary and ill-preserved nature of previously known specimens led certain authorities to doubt their validity. Our assessment of mandibular and dental morphology indicates that K. africanus diverged after Proconsul and Griphopithecus but prior to the last common ancestor of Sivapithecus, extant great apes, and humans. The robustly constructed mandibular symphysis and anterior dentition suggest that incisal biting played as important a role as thick molar enamel in the dietary adaptations of K. africanus. Images Fig. 1 Fig. 2 PMID:8446615

  9. Homeotic Evolution in the Mammalia: Diversification of Therian Axial Seriation and the Morphogenetic Basis of Human Origins

    PubMed Central

    Filler, Aaron G.

    2007-01-01

    Background Despite the rising interest in homeotic genes, little has been known about the course and pattern of evolution of homeotic traits across the mammalian radiation. An array of emerging and diversifying homeotic gradients revealed by this study appear to generate new body plans and drive evolution at a large scale. Methodology/Principal Findings This study identifies and evaluates a set of homeotic gradients across 250 extant and fossil mammalian species and their antecedents over a period of 220 million years. These traits are generally expressed as co-linear gradients along the body axis rather than as distinct segmental identities. Relative position or occurrence sequence vary independently and are subject to polarity reversal and mirroring. Five major gradient modification sets are identified: (1)–quantitative changes of primary segmental identity pattern that appeared at the origin of the tetrapods ; (2)–frame shift relation of costal and vertebral identity which diversifies from the time of amniote origins; (3)–duplication, mirroring, splitting and diversification of the neomorphic laminar process first commencing at the dawn of mammals; (4)–emergence of homologically variable lumbar lateral processes upon commencement of the radiation of therian mammals and ; (5)–inflexions and transpositions of the relative position of the horizontal septum of the body and the neuraxis at the emergence of various orders of therian mammals. Convergent functional changes under homeotic control include laminar articular engagement with septo-neural transposition and ventrally arrayed lumbar transverse process support systems. Conclusion/Significance Clusters of homeotic transformations mark the emergence point of mammals in the Triassic and the radiation of therians in the Cretaceous. A cluster of homeotic changes in the Miocene hominoid Morotopithecus that are still seen in humans supports establishment of a new “hominiform” clade and suggests a homeotic origin for the human upright body plan. PMID:17925867

  10. A spring and wooded habitat at FLK Zinj and their relevance to origins of human behavior

    NASA Astrophysics Data System (ADS)

    Ashley, Gail M.; Barboni, Doris; Dominguez-Rodrigo, Manuel; Bunn, Henry T.; Mabulla, Audax Z. P.; Diez-Martin, Fernando; Barba, Rebeca; Baquedano, Enrique

    2010-11-01

    The 1959 discovery of the hominin fossil Zinjanthropus boisei brought the world's attention to the rich records at Olduvai Gorge, Tanzania. Subsequent excavations of archaeological level 22 (FLK Zinj) Bed I uncovered remains of Homo habilis and a high-density collection of fossils and Oldowan stone tools. The occurrence of this unusual collection of bones and tools at this specific location has been controversial for decades. We present paleoecological data that provide new insights into the origin of FLK Zinj. Our recent excavations 200 m north of the site uncovered a 0.5-m-thick tufa mound draped by Tuff IC, in the same stratigraphic horizon as level 22. Stable isotope analyses indicate that the carbonates were deposited by a freshwater spring. Phytolith analysis of the waxy clay under Tuff IC revealed abundant woody dicotyledon and palm phytoliths, indicating that the site was wooded to densely wooded. The time equivalency and close physical proximity of the two environments indicate the two are related. This study has provided the first documented evidence of springs in Bed I and these data have important implications for the interpretation of hominin behavior in meat acquisition and the ongoing debate on scavenging versus hunting.

  11. N-3 Polyunsaturated Fatty Acids of Marine Origin and Multifocality in Human Breast Cancer

    PubMed Central

    Ouldamer, Lobna; Goupille, Caroline; Vildé, Anne; Arbion, Flavie; Body, Gilles; Chevalier, Stephan; Cottier, Jean Philippe; Bougnoux, Philippe

    2016-01-01

    Objective The microenvironment of breast epithelial tissue may contribute to the clinical expression of breast cancer. Breast epithelial tissue, whether healthy or tumoral, is directly in contact with fat cells, which in turn could influence tumor multifocality. In this pilot study we investigated whether the fatty acid composition of breast adipose tissue differed according to breast cancer focality. Methods Twenty-three consecutive women presenting with non-metastatic breast cancer underwent breast-imaging procedures including Magnetic Resonance Imaging prior to treatment. Breast adipose tissue specimens were collected during breast surgery. We established a biochemical profile of adipose tissue fatty acids by gas chromatography. We assessed whether there were differences according to breast cancer focality. Results We found that decreased levels in breast adipose tissue of docosahexaenoic and eicosapentaenoic acids, the two main polyunsaturated n-3 fatty acids of marine origin, were associated with multifocality. Discussion These differences in lipid content may contribute to mechanisms through which peritumoral adipose tissue fuels breast cancer multifocality. PMID:26812254

  12. Genetics and biology of human ovarian teratomas. I. Cytogenetic analysis and mechanism of origin.

    PubMed

    Surti, U; Hoffner, L; Chakravarti, A; Ferrell, R E

    1990-10-01

    One hundred and two benign, mature ovarian teratomas and two immature, malignant teratomas were karyotyped and scored for centromeric heteromorphisms as part of an ongoing project to determine the chromosomal karyotype and the genetic origin of ovarian teratomas and to assess their utility for gene-centromere mapping. Karyotypic analysis of the benign cases revealed 95 46,XX teratomas and 7 chromosomally abnormal teratomas (47,XXX, 47,XX,+8 [two cases], 47,XX,+15, 48,XX,+7,+12 91,XXXX,-13 [mosaic], 47,XX,-15,+21,+mar). Our study reports on the first cases of tetraploidy and structural rearrangement in benign ovarian teratomas. The two immature cases had modal chromosome numbers of 78 and 49. Centromeric heteromorphisms that were heterozygous in the host were homozygous in 65.2% (n = 58) of the benign teratomas and heterozygous in the remaining 34.8% (n = 31). Chromosome 13 heteromorphisms were the most informative, with 72.7% heterozygosity in hosts. The cytogenetic data indicate that 65% of teratomas are derived from a single germ cell after meiosis I and failure of meiosis II (type II) or endoreduplication of a mature ovum (type III); 35% arise by failure of meiosis I (type I) or mitotic division of premeiotic germ cells (type IV). PMID:2220805

  13. Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer.

    PubMed

    Ju, Young Seok; Alexandrov, Ludmil B; Gerstung, Moritz; Martincorena, Inigo; Nik-Zainal, Serena; Ramakrishna, Manasa; Davies, Helen R; Papaemmanuil, Elli; Gundem, Gunes; Shlien, Adam; Bolli, Niccolo; Behjati, Sam; Tarpey, Patrick S; Nangalia, Jyoti; Massie, Charles E; Butler, Adam P; Teague, Jon W; Vassiliou, George S; Green, Anthony R; Du, Ming-Qing; Unnikrishnan, Ashwin; Pimanda, John E; Teh, Bin Tean; Munshi, Nikhil; Greaves, Mel; Vyas, Paresh; El-Naggar, Adel K; Santarius, Tom; Collins, V Peter; Grundy, Richard; Taylor, Jack A; Hayes, D Neil; Malkin, David; Foster, Christopher S; Warren, Anne Y; Whitaker, Hayley C; Brewer, Daniel; Eeles, Rosalind; Cooper, Colin; Neal, David; Visakorpi, Tapio; Isaacs, William B; Bova, G Steven; Flanagan, Adrienne M; Futreal, P Andrew; Lynch, Andy G; Chinnery, Patrick F; McDermott, Ultan; Stratton, Michael R; Campbell, Peter J

    2014-01-01

    Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C > T and A > G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. A number of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria and is fundamentally linked to mtDNA replication. PMID:25271376

  14. On the multiscale origins of fracture resistance in human bone and its biological degradation

    SciTech Connect

    Zimmermann, Elizabeth A.; Barth, Holly D.; Ritchie, Robert O.

    2012-03-09

    Akin to other mineralized tissues, human cortical bone can resist deformation and fracture due to the nature of its hierarchical structure, which spans the molecular to macroscopic length-scales. Deformation at the smallest scales, mainly through the composite action of the mineral and collagen, contributes to bone?s strength or intrinsic fracture resistance, while crack-tip shielding mechanisms active on the microstructural scale contribute to the extrinsic fracture resistance once cracking begins. The efficiency with which these structural features can resist fracture at both small and large length-scales becomes severely degraded with such factors as aging, irradiation and disease. Indeed aging and irradiation can cause changes to the cross-link profile at fibrillar length-scales as well as changes at the three orders of magnitude larger scale of the osteonal structures, both of which combine to inhibit the bone's overall resistance to the initiation and growth of cracks.

  15. Anti-DNA autoantibody-producing hybridomas of normal human lymphoid cell origin.

    PubMed Central

    Cairns, E; Block, J; Bell, D A

    1984-01-01

    Fusion of human myeloma cell line GM 4672 and tonsillar lymphoid cells from a normal donor resulted in 13 primary hybridomas, which produced IgM anti-single-stranded DNA (ssDNA) antibodies, as determined in enzyme-linked immunosorbent assay. Nine of these primary hybridomas have been cloned and a total of 34 clones were obtained. Supernatants of these cloned hybridomas were tested for binding to ssDNA, native DNA, RNA, low molecular weight supernatant DNA, polydeoxyguanylate-polydeoxycitidylate, polydeoxyadenylate-thymidylate sodium salt, and cardiolipin. Supernatants from all clones but one showed polyspecificity when reacting with the antigens tested. That the clones were true hybridomas rather than transformed lymphoid cells was evidence by IgM anti-DNA antibody secretion, karyotype analysis, and HLA typing. These studies imply that immunoglobulin genes encoding for anti-DNA autoantibodies with a spectrum of nucleic acid specificities similar to systemic lupus erythematosus, exist among normal B lymphocytes. PMID:6470143

  16. Revising the embryonic origin of thyroid C cells in mice and humans

    PubMed Central

    Johansson, Ellen; Andersson, Louise; Örnros, Jessica; Carlsson, Therese; Ingeson-Carlsson, Camilla; Liang, Shawn; Dahlberg, Jakob; Jansson, Svante; Parrillo, Luca; Zoppoli, Pietro; Barila, Guillermo O.; Altschuler, Daniel L.; Padula, Daniela; Lickert, Heiko; Fagman, Henrik; Nilsson, Mikael

    2015-01-01

    Current understanding infers a neural crest origin of thyroid C cells, the major source of calcitonin in mammals and ancestors to neuroendocrine thyroid tumors. The concept is primarily based on investigations in quail–chick chimeras involving fate mapping of neural crest cells to the ultimobranchial glands that regulate Ca2+ homeostasis in birds, reptiles, amphibians and fishes, but whether mammalian C cell development involves a homologous ontogenetic trajectory has not been experimentally verified. With lineage tracing, we now provide direct evidence that Sox17+ anterior endoderm is the only source of differentiated C cells and their progenitors in mice. Like many gut endoderm derivatives, embryonic C cells were found to coexpress pioneer factors forkhead box (Fox) a1 and Foxa2 before neuroendocrine differentiation takes place. In the ultimobranchial body epithelium emerging from pharyngeal pouch endoderm in early organogenesis, differential Foxa1/Foxa2 expression distinguished two spatially separated pools of C cell precursors with different growth properties. A similar expression pattern was recapitulated in medullary thyroid carcinoma cells in vivo, consistent with a growth-promoting role of Foxa1. In contrast to embryonic precursor cells, C cell-derived tumor cells invading the stromal compartment downregulated Foxa2, foregoing epithelial-to-mesenchymal transition designated by loss of E-cadherin; both Foxa2 and E-cadherin were re-expressed at metastatic sites. These findings revise mammalian C cell ontogeny, expand the neuroendocrine repertoire of endoderm and redefine the boundaries of neural crest diversification. The data further underpin distinct functions of Foxa1 and Foxa2 in both embryonic and tumor development. PMID:26395490

  17. On the Origins of Signal Variance in FMRI of the Human Midbrain at High Field

    PubMed Central

    Barry, Robert L.; Coaster, Mariam; Rogers, Baxter P.; Newton, Allen T.; Moore, Jay; Anderson, Adam W.; Zald, David H.; Gore, John C.

    2013-01-01

    Functional Magnetic Resonance Imaging (fMRI) in the midbrain at 7 Tesla suffers from unexpectedly low temporal signal to noise ratio (TSNR) compared to other brain regions. Various methodologies were used in this study to quantitatively identify causes of the noise and signal differences in midbrain fMRI data. The influence of physiological noise sources was examined using RETROICOR, phase regression analysis, and power spectral analyses of contributions in the respiratory and cardiac frequency ranges. The impact of between-shot phase shifts in 3-D multi-shot sequences was tested using a one-dimensional (1-D) phase navigator approach. Additionally, the effects of shared noise influences between regions that were temporally, but not functionally, correlated with the midbrain (adjacent white matter and anterior cerebellum) were investigated via analyses with regressors of ‘no interest’. These attempts to reduce noise did not improve the overall TSNR in the midbrain. In addition, the steady state signal and noise were measured in the midbrain and the visual cortex for resting state data. We observed comparable steady state signals from both the midbrain and the cortex. However, the noise was 2–3 times higher in the midbrain relative to the cortex, confirming that the low TSNR in the midbrain was not due to low signal but rather a result of large signal variance. These temporal variations did not behave as known physiological or other noise sources, and were not mitigated by conventional strategies. Upon further investigation, resting state functional connectivity analysis in the midbrain showed strong intrinsic fluctuations between homologous midbrain regions. These data suggest that the low TSNR in the midbrain may originate from larger signal fluctuations arising from functional connectivity compared to cortex, rather than simply reflecting physiological noise. PMID:23658643

  18. Revising the embryonic origin of thyroid C cells in mice and humans.

    PubMed

    Johansson, Ellen; Andersson, Louise; Örnros, Jessica; Carlsson, Therese; Ingeson-Carlsson, Camilla; Liang, Shawn; Dahlberg, Jakob; Jansson, Svante; Parrillo, Luca; Zoppoli, Pietro; Barila, Guillermo O; Altschuler, Daniel L; Padula, Daniela; Lickert, Heiko; Fagman, Henrik; Nilsson, Mikael

    2015-10-15

    Current understanding infers a neural crest origin of thyroid C cells, the major source of calcitonin in mammals and ancestors to neuroendocrine thyroid tumors. The concept is primarily based on investigations in quail-chick chimeras involving fate mapping of neural crest cells to the ultimobranchial glands that regulate Ca(2+) homeostasis in birds, reptiles, amphibians and fishes, but whether mammalian C cell development involves a homologous ontogenetic trajectory has not been experimentally verified. With lineage tracing, we now provide direct evidence that Sox17+ anterior endoderm is the only source of differentiated C cells and their progenitors in mice. Like many gut endoderm derivatives, embryonic C cells were found to coexpress pioneer factors forkhead box (Fox) a1 and Foxa2 before neuroendocrine differentiation takes place. In the ultimobranchial body epithelium emerging from pharyngeal pouch endoderm in early organogenesis, differential Foxa1/Foxa2 expression distinguished two spatially separated pools of C cell precursors with different growth properties. A similar expression pattern was recapitulated in medullary thyroid carcinoma cells in vivo, consistent with a growth-promoting role of Foxa1. In contrast to embryonic precursor cells, C cell-derived tumor cells invading the stromal compartment downregulated Foxa2, foregoing epithelial-to-mesenchymal transition designated by loss of E-cadherin; both Foxa2 and E-cadherin were re-expressed at metastatic sites. These findings revise mammalian C cell ontogeny, expand the neuroendocrine repertoire of endoderm and redefine the boundaries of neural crest diversification. The data further underpin distinct functions of Foxa1 and Foxa2 in both embryonic and tumor development. PMID:26395490

  19. Cervical cancer epidemiology in foreign women in Northern Italy: role of human papillomavirus prevalence in country of origin.

    PubMed

    Di Felice, Enza; Caroli, Stefania; Paterlini, Luisa; Campari, Cinzia; Prandi, Sonia; Giorgi Rossi, Paolo

    2015-05-01

    This study compares the incidence and treatments of cervical neoplasia in foreigners from high migration countries and Italians in the Reggio Emilia province (Northern Italy) in 2002-2009. Standardized incidence ratios (SIRs) and 95% confidence intervals (95% CI) for cervical intraepithelial neoplasia grade 3 (CIN3) and cancer were calculated for foreigners versus Italian women; foreigners were also classified according to the prevalence of human papillomavirus (HPV) in their country of origin. The proportion of hysterectomies is presented as an indicator of inappropriate surgery in CIN3 and microinvasive cancers. A higher risk was observed in women from high human papillomavirus prevalence countries (HHPVC) both for cancer and for CIN3 (SIR=4.1, 95% CI=2.2-6.9; SIR=2.0, 95% CI 1.7-2.5, respectively), whereas in those from low human papillomavirus prevalence countries (LHPVC), no difference for cancer and a lower risk for CIN3 were observed (SIR=1.0, 95% CI 0.2-2.2; SIR=0.6, 95% CI 0.4-0.8, respectively). A lower CIN3/cancer ratio was found in women from HHPVC (2.6) and in women from LHPVC (3.6) than in Italians (7.4). The percentage of hysterectomies for CIN3 or microinvasive cancers was 3.4 in foreigners and 4.7 in Italians. A higher risk of cervical cancer was found in women from HHPVC compared with Italians and women from LHPVC, suggesting a role of HPV prevalence in the country of origin in the excess risk. The CIN3/cancer ratio was lower for both women from HHPVC and women from LHPVC, also suggesting a role of low screening uptake for cervical cancer incidence in immigrants. PMID:25714783

  20. Peptoniphilus mikwangii sp. nov., isolated from a clinical specimen of human origin.

    PubMed

    Cho, Eugene; Park, Soon-Nang; Shin, Yeseul; Lim, Yun Kyong; Paek, Jayoung; Kim, Hak Kyun; Hwang, Cheol Ho; Jo, Eojin; Jin, Dongchun; Chang, Young-Hyo; Kook, Joong-Ki

    2015-02-01

    A novel Gram-positive, anaerobic, and coccus-shaped bacterium, designated as strain ChDC B134(T), was isolated from a human postoperative infectious lesion in the right maxilla between the lateral incisor and canine and was characterized by polyphasic taxonomic analysis. 16S rRNA gene sequence analysis revealed that the strain ChDC B134(T) belonged to the genus Peptoniphilus, as it showed sequence similarities to Peptoniphilus indolicus KCTC 15023(T) (94.0 %) and Peptoniphilus asaccharolyticus KCTC 3321(T) (93.8 %). The prevalent fatty acids of of strain ChDC B134(T) were C16:0 (20.3 %), C18:1 cis 9 (34.3 %), and C18:0 (13.2 %). The DNA G+C content was 30.9 mol%. The cell wall diamino acid was D-ornithine, which is a property shared by other reference type strains of the genus Peptoniphilus. Based on the results of phenotypic, chemotaxonomic, and phylogenetic analysis, strain ChDC B134(T) (=KCOM 1628(T) = KCTC 15227(T) = JCM 30223(T)) should be classified as the type strain of a novel species of genus Peptoniphilus, for which the name Peptoniphilus mikwangii sp. nov. is proposed. PMID:25319028

  1. Origins and functional impact of copy number variation in the human genome.

    PubMed

    Conrad, Donald F; Pinto, Dalila; Redon, Richard; Feuk, Lars; Gokcumen, Omer; Zhang, Yujun; Aerts, Jan; Andrews, T Daniel; Barnes, Chris; Campbell, Peter; Fitzgerald, Tomas; Hu, Min; Ihm, Chun Hwa; Kristiansson, Kati; Macarthur, Daniel G; Macdonald, Jeffrey R; Onyiah, Ifejinelo; Pang, Andy Wing Chun; Robson, Sam; Stirrups, Kathy; Valsesia, Armand; Walter, Klaudia; Wei, John; Tyler-Smith, Chris; Carter, Nigel P; Lee, Charles; Scherer, Stephen W; Hurles, Matthew E

    2010-04-01

    Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs. PMID:19812545

  2. Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes.

    PubMed

    Maher, Geoffrey J; McGowan, Simon J; Giannoulatou, Eleni; Verrill, Clare; Goriely, Anne; Wilkie, Andrew O M

    2016-03-01

    De novo point mutations arise predominantly in the male germline and increase in frequency with age, but it has not previously been possible to locate specific, identifiable mutations directly within the seminiferous tubules of human testes. Using microdissection of tubules exhibiting altered expression of the spermatogonial markers MAGEA4, FGFR3, and phospho-AKT, whole genome amplification, and DNA sequencing, we establish an in situ strategy for discovery and analysis of pathogenic de novo mutations. In 14 testes from men aged 39-90 y, we identified 11 distinct gain-of-function mutations in five genes (fibroblast growth factor receptors FGFR2 and FGFR3, tyrosine phosphatase PTPN11, and RAS oncogene homologs HRAS and KRAS) from 16 of 22 tubules analyzed; all mutations have known associations with severe diseases, ranging from congenital or perinatal lethal disorders to somatically acquired cancers. These results support proposed selfish selection of spermatogonial mutations affecting growth factor receptor-RAS signaling, highlight its prevalence in older men, and enable direct visualization of the microscopic anatomy of elongated mutant clones. PMID:26858415

  3. Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes

    PubMed Central

    Maher, Geoffrey J.; McGowan, Simon J.; Giannoulatou, Eleni; Verrill, Clare; Goriely, Anne; Wilkie, Andrew O. M.

    2016-01-01

    De novo point mutations arise predominantly in the male germline and increase in frequency with age, but it has not previously been possible to locate specific, identifiable mutations directly within the seminiferous tubules of human testes. Using microdissection of tubules exhibiting altered expression of the spermatogonial markers MAGEA4, FGFR3, and phospho-AKT, whole genome amplification, and DNA sequencing, we establish an in situ strategy for discovery and analysis of pathogenic de novo mutations. In 14 testes from men aged 39–90 y, we identified 11 distinct gain-of-function mutations in five genes (fibroblast growth factor receptors FGFR2 and FGFR3, tyrosine phosphatase PTPN11, and RAS oncogene homologs HRAS and KRAS) from 16 of 22 tubules analyzed; all mutations have known associations with severe diseases, ranging from congenital or perinatal lethal disorders to somatically acquired cancers. These results support proposed selfish selection of spermatogonial mutations affecting growth factor receptor-RAS signaling, highlight its prevalence in older men, and enable direct visualization of the microscopic anatomy of elongated mutant clones. PMID:26858415

  4. African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era

    PubMed Central

    Kasembeli, Alex N; Duarte, Raquel; Ramsay, Michèle; Naicker, Saraladevi

    2015-01-01

    Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era. PMID:25949944

  5. Origin, Possible Function and Fate of Follicular Cells in the Anterior Lobe of the Human Pituitary

    PubMed Central

    Horvath, E.; Kovacs, K.; Penz, G.; Ezrin, C.

    1974-01-01

    In human anterior pituitaries, follicular structures were found to develop by transformation of various types of glandular cells around foci of ruptured granulated cells undergoing destruction. In phase I, junctional complexes between granulated cells, as well as microvilli at the luminal surfaces of cell membranes, are formed. In phase II, degranulation and dedifferentiation of cytoplasm dominate the picture. Phase III follicular cells are practically devoid of secretory granules and other ultrastructural features characteristic of granulated cells. The participation of cell types in follicle formation does not appear to be limited. The follicular content in phase I-II is clearly recognizable as cellular debris from adenohypophysiocytes. These findings indicate that neither follicles nor junctional complexes are necessarily permanent structures of the anterior pituitary. It can be assumed that substances escaping from ruptured granulated cells may induce the formation of junctional complexes between adjacent cells. ImagesFig 5Fig 6Fig 7Fig 8Fig 9Fig 1Fig 2Fig 10Fig 3Fig 4 PMID:4447128

  6. Origins and functional impact of copy number variation in the human genome

    PubMed Central

    Conrad, Donald F.; Pinto, Dalila; Redon, Richard; Feuk, Lars; Gokcumen, Omer; Zhang, Yujun; Aerts, Jan; Andrews, T. Daniel; Barnes, Chris; Campbell, Peter; Fitzgerald, Tomas; Hu, Min; Ihm, Chun Hwa; Kristiansson, Kati; MacArthur, Daniel G.; MacDonald, Jeffrey R.; Onyiah, Ifejinelo; Pang, Andy Wing Chun; Robson, Sam; Stirrups, Kathy; Valsesia, Armand; Walter, Klaudia; Wei, John; Tyler-Smith, Chris; Carter, Nigel P.; Lee, Charles; Scherer, Stephen W.; Hurles, Matthew E.

    2012-01-01

    Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs. PMID:19812545

  7. Aberrant Phenotype in Human Endothelial Cells of Diabetic Origin: Implications for Saphenous Vein Graft Failure?

    PubMed Central

    Roberts, Anna C.; Gohil, Jai; Hudson, Laura; Connolly, Kyle; Warburton, Philip; Suman, Rakesh; O'Toole, Peter; O'Regan, David J.; Turner, Neil A.; Riches, Kirsten; Porter, Karen E.

    2015-01-01

    Type 2 diabetes (T2DM) confers increased risk of endothelial dysfunction, coronary heart disease, and vulnerability to vein graft failure after bypass grafting, despite glycaemic control. This study explored the concept that endothelial cells (EC) cultured from T2DM and nondiabetic (ND) patients are phenotypically and functionally distinct. Cultured human saphenous vein- (SV-) EC were compared between T2DM and ND patients in parallel. Proliferation, migration, and in vitro angiogenesis assays were performed; western blotting was used to quantify phosphorylation of Akt, ERK, and eNOS. The ability of diabetic stimuli (hyperglycaemia, TNF-α, and palmitate) to modulate angiogenic potential of ND-EC was also explored. T2DM-EC displayed reduced migration (~30%) and angiogenesis (~40%) compared with ND-EC and a modest, nonsignificant trend to reduced proliferation. Significant inhibition of Akt and eNOS, but not ERK phosphorylation, was observed in T2DM cells. Hyperglycaemia did not modify ND-EC function, but TNF-α and palmitate significantly reduced angiogenic capacity (by 27% and 43%, resp.), effects mimicked by Akt inhibition. Aberrancies of EC function may help to explain the increased risk of SV graft failure in T2DM patients. This study highlights the importance of other potentially contributing factors in addition to hyperglycaemia that may inflict injury and long-term dysfunction to the homeostatic capacity of the endothelium. PMID:25950006

  8. Exploring the Molecular Origins of Protein Dynamics in the Active Site of Human Carbonic Anhydrase II

    PubMed Central

    Hill, Sarah E.; Bandaria, Jigar N.; Fox, Michelle; Vanderah, Elizabeth; Kohen, Amnon; Cheatum, Christopher M.

    2009-01-01

    We present three-pulse vibrational echo measurements of azide ion bound to the active site Zn of human carbonic anhydrase II (HCA II) and of two separate active-site mutants Thr199 → Ala (T199A) and Leu198 → Phe (L198F). Because structural motions of the protein active site influence the frequency of bound ligands, the differences in the time scales of the frequency-frequency correlation functions (FFCFs) obtained from global fits to each set of data allow us to make inferences about the time scales of the active site dynamics of HCA II. Surprisingly, the deletion of a potential electrostatic interaction in T199A results in very little change in the FFCF, but the insertion of the bulky phenylalanine ring in L198F causes much faster dynamics. We conclude that the fast, sub-picosecond time scale in the correlation function is attributable to hydrogen bond dynamics, and the slow, apparently static contribution is due to the conformational flexibility of Zn-bound azide in the active site. PMID:19637848

  9. Early origins of adult disease: approaches for investigating the programmable epigenome in humans, nonhuman primates, and rodents.

    PubMed

    Ganu, Radhika S; Harris, R Alan; Collins, Kiara; Aagaard, Kjersti M

    2012-01-01

    According to the developmental origins of health and disease hypothesis, in utero experiences reprogram an individual for immediate adaptation to gestational perturbations, with the sequelae of later-in-life risk of metabolic disease. An altered gestational milieu with resultant adult metabolic disease has been observed in instances of both in utero constraint (e.g., from famine or uteroplacental insufficiency) and overt caloric abundance (e.g., from a maternal high-fat, caloric-dense diet). The commonality of the adult metabolic phenotype begs the question of how diverse in utero experiences (i.e., reprogramming events) converge on common metabolic pathways and how the memory of these events is maintained across the lifespan. We and others have investigated the molecular mechanisms underlying fetal programming and observed that epigenetic modifications to the fetal and placental epigenome accompany these reprogramming events. Based on several lines of emerging data in human and nonhuman primates, it is now felt that modified epigenetic signature--and the histone code in particular--underlies alterations in postnatal gene expression and metabolic pathways central to accurate functioning and maintenance of health. Because of the tissue lineage specificity of many of these modifications, nonhuman primates serve as an apt model system for the capacity to recapitulate human gene expression and regulation during development. This review summarizes recent epigenetic advances using rodent and primate (both human and nonhuman) models during in utero development and contributing to adult diseases later in life. PMID:23744969

  10. Original 2-(3-Alkoxy-1H-pyrazol-1-yl)azines Inhibitors of Human Dihydroorotate Dehydrogenase (DHODH).

    PubMed

    Lucas-Hourani, Marianne; Munier-Lehmann, Hélène; El Mazouni, Farah; Malmquist, Nicholas A; Harpon, Jane; Coutant, Eloi P; Guillou, Sandrine; Helynck, Olivier; Noel, Anne; Scherf, Artur; Phillips, Margaret A; Tangy, Frédéric; Vidalain, Pierre-Olivier; Janin, Yves L

    2015-07-23

    Following our discovery of human dihydroorotate dehydrogenase (DHODH) inhibition by 2-(3-alkoxy-1H-pyrazol-1-yl)pyrimidine derivatives as well as 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-methylpyridine, we describe here the syntheses and evaluation of an array of azine-bearing analogues. As in our previous report, the structure-activity study of this series of human DHODH inhibitors was based on a phenotypic assay measuring measles virus replication. Among other inhibitors, this round of syntheses and biological evaluation iteration led to the highly active 5-cyclopropyl-2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-3-fluoropyridine. Inhibition of DHODH by this compound was confirmed in an array of in vitro assays, including enzymatic tests and cell-based assays for viral replication and cellular growth. This molecule was found to be more active than the known inhibitors of DHODH, brequinar and teriflunomide, thus opening perspectives for its use as a tool or for the design of an original series of immunosuppressive agent. Moreover, because other series of inhibitors of human DHODH have been found to also affect Plasmodium falciparum DHODH, all the compounds were assayed for their effect on P. falciparum growth. However, the modest in vitro inhibition solely observed for two compounds did not correlate with their inhibition of P. falciparum DHODH. PMID:26079043

  11. Early Origins of Adult Disease: Approaches for Investigating the Programmable Epigenome in Humans, Nonhuman Primates, and Rodents

    PubMed Central

    Ganu, Radhika S.; Harris, R. Alan; Collins, Kiara; Aagaard, Kjersti M.

    2012-01-01

    According to the developmental origins of health and disease hypothesis, in utero experiences reprogram an individual for immediate adaptation to gestational perturbations, with the sequelae of later-in-life risk of metabolic disease. An altered gestational milieu with resultant adult metabolic disease has been observed in instances of both in utero constraint (e.g., from famine or uteroplacental insufficiency) and overt caloric abundance (e.g., from a maternal high-fat, caloric-dense diet). The commonality of the adult metabolic phenotype begs the question of how diverse in utero experiences (i.e., reprogramming events) converge on common metabolic pathways and how the memory of these events is maintained across the lifespan. We and others have investigated the molecular mechanisms underlying fetal programming and observed that epigenetic modifications to the fetal and placental epigenome accompany these reprogramming events. Based on several lines of emerging data in human and nonhuman primates, it is now felt that modified epigenetic signature—and the histone code in particular—underlies alterations in postnatal gene expression and metabolic pathways central to accurate functioning and maintenance of health. Because of the tissue lineage specificity of many of these modifications, nonhuman primates serve as an apt model system for the capacity to recapitulate human gene expression and regulation during development. This review summarizes recent epigenetic advances using rodent and primate (both human and nonhuman) models during in utero development and contributing to adult diseases later in life. PMID:23744969

  12. Timing of human preimplantation embryonic development is confounded by embryo origin

    PubMed Central

    Kirkegaard, K.; Sundvall, L.; Erlandsen, M.; Hindkjær, J.J.; Knudsen, U.B.; Ingerslev, H.J.

    2016-01-01

    STUDY QUESTION To what extent do patient- and treatment-related factors explain the variation in morphokinetic parameters proposed as embryo viability markers? SUMMARY ANSWER Up to 31% of the observed variation in timing of embryo development can be explained by embryo origin, but no single factor elicits a systematic influence. WHAT IS KNOWN ALREADY Several studies report that culture conditions, patient characteristics and treatment influence timing of embryo development, which have promoted the perception that each clinic must develop individual models. Most of the studies have, however, treated embryos from one patient as independent observations, and only very few studies that evaluate the influence from patient- and treatment-related factors on timing of development or time-lapse parameters as predictors of viability have controlled for confounding, which implies a high risk of overestimating the statistical significance of potential correlations. STUDY DESIGN, SIZE, DURATION Infertile patients were prospectively recruited to a cohort study at a hospital fertility clinic from February 2011 to May 2013. Patients aged <38 years without endometriosis were eligible if ≥8 oocytes were retrieved. Patients were included only once. All embryos were monitored for 6 days in a time-lapse incubator. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 1507 embryos from 243 patients were included. The influence of fertilization method, BMI, maternal age, FSH dose and number of previous cycles on timing of t2-t5, duration of the 2- and 3-cell stage, and development of a blastocoel (tEB) and full blastocoel (tFB) was tested in multivariate, multilevel linear regression analysis. Predictive parameters for live birth were tested in a logistic regression analysis for 223 single transferred blastocysts, where time-lapse parameters were investigated along with patient and embryo characteristics. MAIN RESULTS AND THE ROLE OF CHANCE Moderate intra-class correlation coefficients (0.16–0.31) were observed for all parameters except duration of the 3-cell stage, which demonstrates that embryos from one patient elicit clustering at a patient level. No single patient- and treatment-related factor was found to systematically influence the timing from cleavage to blastocyst stage, which indicates that no individual patient-related factor can be identified that separately explains the clustering throughout the entire developmental stages. The blastocyst parameters were more affected by patient-related factors than cleavage stage parameters, as tEB occurred significantly later with older age (0.29 h/year (95% confidence interval: CI 0.03; 0.56)), while both tEB and tFB occurred significantly later with increasing dose of FSH (tEB: 0.12 h/100 IU FSH (95% CI 0.01;0.24); tFB 0.14 h/100 IU FSH (95% CI 0.03;0.27)) and with more previous attempts (tEB: 1.2 h/attempt (95% CI 0.01;2.5); tFB 1.4 h/attempt (0.10;2.7)). Fertilization method affected timing of the first division, with ICSI embryos cleaving significantly faster than IVF embryos (−3.6% (95% CI −6.4; −0.77)), whereas no difference was found in the subsequent divisions. The univariable regression analysis identified female age, cumulative FSH dose, degree of blastocyst expansion, score of the inner cell mass and timing of full blastocyst formation as predictors of live birth. The timing of full blastocyst formation (tFB) did not remain significant when adjusting for age, number of previous cycles and cumulative FSH dose, which were the parameters shown to influence tFB in the mixed regression model. LIMITATIONS, REASONS FOR CAUTION Only good prognosis patients were enrolled, so these results may not be generalized to all infertile women. Not all patient-related factors were investigated. WIDER IMPLICATIONS OF THE FINDINGS Our findings underline the importance of treating embryos as dependent observations and suggest a high risk of patient-based confounding in retrospective studies. The impact of confounders and the embryo origin needs to be addressed in order to apply appropriate statistical models in observational studies. Furthermore, this observation emphasizes the need for RCTs for evaluating use of time-lapse parameters for embryo selection. STUDY FUNDING/COMPETING INTERESTS Funding for the cohort study was provided by the Lippert Foundation, the Toyota Foundation, the Aase og Einar Danielsen foundation and NordicInfu Care research grant. Research at the Fertility Clinic, Aarhus University Hospital is supported by an unrestricted grant from MSD and Ferring. K.K. is funded by a grant from the Danish Council for Independent Research Medical Sciences. The authors declare no competing interest. PMID:26637491

  13. Genome-Wide and Paternal Diversity Reveal a Recent Origin of Human Populations in North Africa

    PubMed Central

    Martínez-Cruz, Begoña; Zalloua, Pierre; Benammar Elgaaied, Amel; Comas, David

    2013-01-01

    The geostrategic location of North Africa as a crossroad between three continents and as a stepping-stone outside Africa has evoked anthropological and genetic interest in this region. Numerous studies have described the genetic landscape of the human population in North Africa employing paternal, maternal, and biparental molecular markers. However, information from these markers which have different inheritance patterns has been mostly assessed independently, resulting in an incomplete description of the region. In this study, we analyze uniparental and genome-wide markers examining similarities or contrasts in the results and consequently provide a comprehensive description of the evolutionary history of North Africa populations. Our results show that both males and females in North Africa underwent a similar admixture history with slight differences in the proportions of admixture components. Consequently, genome-wide diversity show similar patterns with admixture tests suggesting North Africans are a mixture of ancestral populations related to current Africans and Eurasians with more affinity towards the out-of-Africa populations than to sub-Saharan Africans. We estimate from the paternal lineages that most North Africans emerged ∼15,000 years ago during the last glacial warming and that population splits started after the desiccation of the Sahara. Although most North Africans share a common admixture history, the Tunisian Berbers show long periods of genetic isolation and appear to have diverged from surrounding populations without subsequent mixture. On the other hand, continuous gene flow from the Middle East made Egyptians genetically closer to Eurasians than to other North Africans. We show that genetic diversity of today's North Africans mostly captures patterns from migrations post Last Glacial Maximum and therefore may be insufficient to inform on the initial population of the region during the Middle Paleolithic period. PMID:24312208

  14. Morphometric Study of Nasal Bone and Piriform Aperture in Human Dry Skull of Indian Origin

    PubMed Central

    Dixit, Aparna; Rani, Mamta

    2016-01-01

    Introduction Nasal bone and piriform aperture shows racial and geographical differences because of variable climate. The aim of this study was to evaluate the dimensions (maximal width and length), the size and the shape of the piriform aperture (PA) and their sexual dimorphism in North Indian adult. Materials and Methods In this observational study, dimension of piriform aperture and nasal bone were measured using digital vernier caliper after assessing landmarks around the piriform aperture on the norma frontalis in Frankfurt plane in 40 skull of Indian orgin. Results The mean width of the piriform aperture was 24.9±1.59 mm in males and 22.77±1.57 mm in females, the mean length was 29.57±3.28mm in females and 31.16±3.58mm in males. The difference between males and females was significant, and our data correlates well with the previously data acquired from humans skulls. Most of North Indian skulls have platyrhine type of piriform aperture (triangular to oval shape with pyriform aperture index of 0.79). Mean length and width of nasal bone were 17.58±2.47mm and 12.1±0.97mm respectively without sexual. Conclusion Shape and size analysis of the piriform aperture and nasal bone showed the existence of a significant sexual dimorphism. These results encourage us to go further with functional and imaging correlations. This study will also be helpful in forensic research and anthropology. PMID:26894050

  15. Human adult stem cells from diverse origins: an overview from multiparametric immunophenotyping to clinical applications.

    PubMed

    Sousa, Bruna R; Parreira, Ricardo C; Fonseca, Emerson A; Amaya, Maria J; Tonelli, Fernanda M P; Lacerda, Samyra M S N; Lalwani, Pritesh; Santos, Anderson K; Gomes, Katia N; Ulrich, Henning; Kihara, Alexandre H; Resende, Rodrigo R

    2014-01-01

    Stem cells are known for their capacity to self-renew and differentiate into at least one specialized cell type. Mesenchymal stem cells (MSCs) were isolated initially from bone marrow but are now known to exist in all vascularized organ or tissue in adults. MSCs are particularly relevant for therapy due to their simplicity of isolation and cultivation. The International Society for Cellular Therapy (ISCT) has proposed a set of standards to define hMSCs for laboratory investigations and preclinical studies: adherence to plastic in standard culture conditions; in vitro differentiation into osteoblasts, adipocytes, and chondroblasts; specific surface antigen expression in which ≥95% of the cells express the antigens recognized by CD105, CD73, and CD90, with the same cells lacking (≤2% positive) the antigens CD45, CD34, CD14 or CD11b, CD79a or CD19, and HLA-DR. In this review we will take an historical overview of how umbilical cord blood, bone marrow, adipose-derived, placental and amniotic fluid, and menstrual blood stem cells, the major sources of human MSC, can be obtained, identified and how they are being used in clinical trials to cure and treat a very broad range of conditions, including heart, hepatic, and neurodegenerative diseases. An overview of protocols for differentiation into hepatocytes, cardiomyocytes, neuronal, adipose, chondrocytes, and osteoblast cells are highlighted. We also discuss a new source of stem cells, induced pluripotent stem cells (iPS cells) and some pathways, which are common to MSCs in maintaining their pluripotent state. PMID:24700575

  16. Heterogeneity among Virulence and Antimicrobial Resistance Gene Profiles of Extraintestinal Escherichia coli Isolates of Animal and Human Origin

    PubMed Central

    Maynard, Christine; Bekal, Sadjia; Sanschagrin, Franois; Levesque, Roger C.; Brousseau, Roland; Masson, Luke; Larivire, Serge; Harel, Jose

    2004-01-01

    Extraintestinal pathogenic Escherichia coli (ExPEC) isolates collected from different infected animals and from human patients with extraintestinal infections in 2001 were characterized for their phenotypic and genotypic antimicrobial resistance profiles, genotypes, and key virulence factors. Among the 10 antimicrobial agents tested, resistance to ampicillin, tetracycline, and sulfonamides was most frequent. Multiresistant strains were found in both the animal and the human groups of isolates. Resistance gene distribution was assessed by colony hybridization. Similar antibiotic resistance patterns could be observed in the animal and the human isolates. Although some resistance genes, such as blaTEM, sulI, and sulII, were equally represented in the animal and human ExPEC isolates, differences in the distributions of tetracycline [tet(D)], chloramphenicol (catI, catIII, and floR), and trimethoprim (dhfrI, dhfrV, dhfrVII, and dhfrXIII) resistance genes were observed between the animal and the human isolates. Approximately one-third of the ExPEC isolates possessed a class 1 integron. The four major different variable regions of the class 1 integron contained aminoglycoside (aadA1, aadA2, aadA5, and aadA6) and/or trimethoprim (dhfrIb, dhfrXII, and dhfrXVII) resistance genes. The ExPEC strains belonged to different phylogenetic groups, depending on their host origin. Strains isolated from animal tissues belonged to either a commensal group (group A or B1) or a virulent group (group B2 or D), while the majority of the human isolates belonged to a virulent group (group B2 or D). Although the limited number of isolates evaluated in the present study prevents firm epidemiological conclusions from being made, on a more global scale, these data demonstrate that extraintestinal isolates of E. coli can possess relatively distinct intra- and intergroup resistance gene profiles, with animal isolates presenting a more heterogeneous group than human isolates. PMID:15583263

  17. Human Papillomavirus and Cystic Node Metastasis in Oropharyngeal Cancer and Cancer of Unknown Primary Origin

    PubMed Central

    Yasui, Toshimichi; Morii, Eiichi; Yamamoto, Yoshifumi; Yoshii, Tadashi; Takenaka, Yukinori; Nakahara, Susumu; Todo, Takeshi; Inohara, Hidenori

    2014-01-01

    The clinical significance of human papillomavirus (HPV) in neck node metastasis from cancer of unknown primary (CUP) is not well established. We aimed to address the relationship of HPV status between node metastasis and the primary tumor, and also the relevance of HPV status regarding radiographically detected cystic node metastasis in head and neck squamous cell carcinoma (HNSCC) and CUP. HPV DNA was examined in 68 matched pairs of node metastasis and primary tumor, and in node metastasis from 27 CUPs. In surgically treated CUPs, p16 was examined immunohistochemically. When tonsillectomy proved occult tonsillar cancer in CUP, HPV DNA and p16 were also examined in the occult primary. Cystic node metastasis on contrast-enhanced computed tomography scans was correlated with the primary site and HPV status in another series of 255 HNSCCs and CUPs with known HPV status. Node metastasis was HPV-positive in 19/37 (51%) oropharyngeal SCCs (OPSCCs) and 10/27 (37%) CUPs, but not in non-OPSCCs. Fluid was collected from cystic node metastasis using fine needle aspiration in two OPSCCs and one CUP, and all fluid collections were HPV-positive. HPV status, including the presence of HPV DNA, genotype, and physical status, as well as the expression pattern of p16 were consistent between node metastasis and primary or occult primary tumor. Occult tonsillar cancer was found more frequently in p16-positive CUP than in p16-negative CUP (odds ratio (OR), 39.0; 95% confidence interval (CI), 1.4–377.8; P = 0.02). Radiographically, cystic node metastasis was specific to OPSCC and CUP, and was associated with HPV positivity relative to necrotic or solid node metastasis (OR, 6.2; 95% CI, 1.2–45.7; P = 0.03). In conclusion, HPV status remains unchanged after metastasis. The occult primary of HPV-positive CUP is most probably localized in the oropharynx. HPV status determined from fine needle aspirates facilitates the diagnosis of cystic node metastasis. PMID:24752007

  18. Novel isolation strategy to deliver pure fetal-origin and maternal-origin mesenchymal stem cell (MSC) populations from human term placenta.

    PubMed

    Patel, J; Shafiee, A; Wang, W; Fisk, N M; Khosrotehrani, K

    2014-11-01

    The placenta is an abundant source of mesenchymal stem/stromal cells (MSC). Although presumed of translationally-advantageous fetal origin, the literature instead suggests a high incidence of either contaminating or pure maternal MSC. Despite definitional criteria that MSC are CD34-, increasing evidence suggests that fetal MSC may be CD34 positive in vivo. We flow sorted term placental digests based on CD34+ expression and exploited differential culture media to isolate separately pure fetal and maternal MSC populations. This method has considerable translational implications, in particular to clinical trials underway with "placental" MSC of uncertain or decidual origin. PMID:25239220

  19. A Novel Human-Infection-Derived Bacterium Provides Insights into the Evolutionary Origins of Mutualistic Insect–Bacterial Symbioses

    PubMed Central

    Clayton, Adam L.; Oakeson, Kelly F.; Gutin, Maria; Pontes, Arthur; Dunn, Diane M.; von Niederhausern, Andrew C.; Weiss, Robert B.; Fisher, Mark; Dale, Colin

    2012-01-01

    Despite extensive study, little is known about the origins of the mutualistic bacterial endosymbionts that inhabit approximately 10% of the world's insects. In this study, we characterized a novel opportunistic human pathogen, designated “strain HS,” and found that it is a close relative of the insect endosymbiont Sodalis glossinidius. Our results indicate that ancestral relatives of strain HS have served as progenitors for the independent descent of Sodalis-allied endosymbionts found in several insect hosts. Comparative analyses indicate that the gene inventories of the insect endosymbionts were independently derived from a common ancestral template through a combination of irreversible degenerative changes. Our results provide compelling support for the notion that mutualists evolve from pathogenic progenitors. They also elucidate the role of degenerative evolutionary processes in shaping the gene inventories of symbiotic bacteria at a very early stage in these mutualistic associations. PMID:23166503

  20. Relationships between hair growth rate and morphological parameters of human straight hair: a same law above ethnical origins?

    PubMed

    Baque, C Saint Olive; Zhou, J; Gu, W; Collaudin, C; Kravtchenko, S; Kempf, J Y; Saint-Léger, D

    2012-04-01

    After measurement of individual growth rates, natural hair fibres from Asian and Caucasian subjects were analysed using scanning electron microscopy. In total, more than 1000 hairs were analysed. Measurements of diameter, medulla and interscale distance (average distance between two successive cuticle scales) show these parameters strongly correlated with hair growth rate. A thicker hair fibre corresponds to a faster growth rate, a shorter interscale distance and greater probability to have a medulla, and vice versa, a thin hair fibre shows slower growth rate, a larger interscale distance and a lower probability to have a medulla. Very interestingly, this finding appears to be unrelated to the ethnic origin of the subjects, suggesting a common characteristic of human hair, at least for the straight or semi-straight hair studied. From a practical viewpoint, this finding clearly suggests an alternative method for measuring hair growth rates, by measuring the interscale distance, which appears easier than using common laboratory equipments. PMID:21951315

  1. Let's Start at the Very Beginning: The Impact of Program Origins and Negotiated Community-University Partnerships on Canadian Radical Humanities Programs

    ERIC Educational Resources Information Center

    Groen, Janet; Hyland-Russell, Tara

    2012-01-01

    This article examines the community-university partnerships and the planning process of three Canadian Radical Humanities programs: programs that offer university entry-level humanities to adult learners on the margins of society. Examining these three iterations has revealed the significance of program origins, particularly the introduction of…

  2. Evolution of Shiga toxin-producing Escherichia coli O157: eight major lineages of human and cattle origin strain signature genotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cattle are a major reservoir for Shiga toxin-producing Escherichia coli O157 (STEC O157) and harbor genetic subtypes that do not all associate with human disease. STEC O157 evolved from an E. coli O55:H7 progenitor, however, depauperate nucleotide polymorphism discovery from cattle and human origin...

  3. Phylogenetic Classification of Escherichia coli O157:H7 Isolates of Human and Bovine Origin Using a Novel Set of Nucleotide Polymorphisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background Cattle are a reservoir of Shiga toxin-producing Escherichia coli O157:H7 (STEC O157), and are known to harbor subtypes not typically found in clinically-ill humans. Consequently, nucleotide polymorphisms previously discovered via isolates originating from human outbreaks may be restricte...

  4. Phylogenetic Classification of Escherichia coli O157:H7 Strains of Human and Bovine Origin Using a Novel Set of Nucleotide Polymorphisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background Cattle are a reservoir of Shiga toxin-producing Escherichia coli O157:H7 (STEC O157), and are known to harbor subtypes not typically found in clinically-ill humans. Consequently, nucleotide polymorphisms previously discovered via isolates originating from human outbreaks may be restricte...

  5. Immortalization of human WI38 cells is associated with differential activation of the c-myc origins.

    PubMed

    Tao, L; Dong, Z; Zannis-Hadjopoulos, M; Price, G B

    2001-01-01

    To study the possible relationships between origin activities and cellular processes leading to malignancy, we used an isogenic system of human embryo lung fibroblast cells WI38 and a SV40-transformed variant, WI38 VA13 2RA (WI38(SV40)). We found that the activities of all initiation sites at the c-myc locus were approximately two-fold as high in WI38(SV40) cells as in WI38 cells. Thus, higher initiation frequency of origins at certain loci is induced with cell immortalization, one of the steps in the multi-step process leading to malignancy. We measured the activities of the four c-myc promoters P0, P1, P2, and P3 with nuclear runon assay in the two cell lines in order to detect potential individual promoter changes that may be also associated with immortalization by SV40 virus. The results show that the activities of the promoters P0, P1, and P3 did not significantly change, but the activity of the major promoter P2 in WI38(SV40) cells was about 7.5- to 8.0-fold as high as that in WI38 cells. The increased activity of promoter P2, although approximately 600 bp downstream of one of the major DNA replication initiation sites, had no preferential influence on the major sites of origin activity. Since the distribution of nascent strand abundance was not significantly altered, binding of transcription factors does not seem to facilitate the assembly of pre-replication complex (pre-RC) or otherwise preferentially alter the activities of the DNA replication proteins at this major initiation site. PMID:11500928

  6. Aberrant firing of replication origins potentially explains intragenic nonrecurrent rearrangements within genes, including the human DMD gene

    PubMed Central

    Ankala, Arunkanth; Kohn, Jordan N.; Hegde, Anisha; Meka, Arjun; Ephrem, Chin Lip Hon; Askree, Syed H.; Bhide, Shruti; Hegde, Madhuri R.

    2012-01-01

    Non-allelic homologous recombination (NAHR), non-homologous end joining (NHEJ), and microhomology-mediated replication-dependent recombination (MMRDR) have all been put forward as mechanisms to explain DNA rearrangements associated with genomic disorders. However, many nonrecurrent rearrangements in humans remain unexplained. To further investigate the mutation mechanisms of these copy number variations (CNVs), we performed breakpoint mapping analysis for 62 clinical cases with intragenic deletions in the human DMD gene (50 cases) and other known disease-causing genes (one PCCB, one IVD, one DBT, three PAH, one STK11, one HEXB, three DBT, one HRPT1, and one EMD cases). While repetitive elements were found in only four individual cases, three involving DMD and one HEXB gene, microhomologies (2–10 bp) were observed at breakpoint junctions in 56% and insertions ranging from 1 to 48 bp were seen in 16 of the total 62 cases. Among these insertions, we observed evidence for tandem repetitions of short segments (5–20 bp) of reference sequence proximal to the breakpoints in six individual DMD cases (six repeats in one, four repeats in three, two repeats in one, and one repeat in one case), strongly indicating attempts by the replication machinery to surpass the stalled replication fork. We provide evidence of a novel template slippage event during replication rescue. With a deeper insight into the complex process of replication and its rescue during origin failure, brought forward by recent studies, we propose a hypothesis based on aberrant firing of replication origins to explain intragenic nonrecurrent rearrangements within genes, including the DMD gene. PMID:22090376

  7. Determination of gallium originated from a gallium-based anticancer drug in human urine using ICP-MS.

    PubMed

    Filatova, Darya G; Seregina, Irina F; Foteeva, Lidia S; Pukhov, Vladimir V; Timerbaev, Andrei R; Bolshov, Mikhail A

    2011-05-01

    Urine analysis gives an insight into the excretion of the administered drug which is related to its reactivity and toxicity. In this work, the capability of inductively coupled plasma mass spectrometry (ICP-MS) to measure ultratrace metal levels was utilized for rapid assaying of gallium originating from the novel gallium anticancer drug, tris(8-quinolinolato)gallium(III) (GaQ(3)), in human urine. Sample dilution with 1% (v/v) HNO(3) as the only required pre-treatment was shown to prevent contamination of the sample introduction system and to reduce polyatomic interferences from sample components. The origin of the blank signal at masses of gallium isotopes, 71 and 69, was investigated using high-resolution ICP-MS and attributed, respectively, to the formation of (36)Ar(35)Cl(+) and (40)Ar(31)P(+) ions and, tentatively, to a triplet of doubly charged ions of Ba, La, and Ce. The accuracy and precision performance was tested by evaluating a set of parameters for analytical method validation. The developed assay has been applied for the determination of gallium in urine samples spiked with GaQ(3). The achieved recoveries (95-102%) and quantification limit of 0.2 μg L(-1) emphasize the practical applicability of the presented analytical approach to monitor renal elimination of GaQ(3) at all dose levels in clinical trials that are currently in progress. PMID:21359996

  8. A crypto-Dravidian origin for the nontribal communities of South India based on human leukocyte antigen class I diversity.

    PubMed

    Thomas, R; Nair, S B; Banerjee, M

    2006-09-01

    The Dravidian communities are considered to be the original inhabitants of India, now restricted to South India. The southern most state, Kerala, is socio-culturally stratified into Hindus, Muslims and Christians on the basis of religion. The origin of these religious communities in Kerala is considered to be unique in comparison with that in other parts of the country. These communities were later influenced by the hierarchical caste structure established by the Hindu Brahmins. In the present study, we compared six nontribal (Namboothiri, Nair, Ezhava, Pulaya, Malabar Muslim and Syrian Christian) communities belonging to the major religious groups in Kerala (Hindu, Muslim and Christian) based on the human leukocyte antigen (HLA)-A, -B and -C diversity. Our aim was to understand the genomic substructuring associated with the changing social scenario in various caste and religious groups and compare it with the Dravidian tribal and other world populations. The present study reveals that the HLA diversity of the Dravidian communities is very distinct from that in the other world populations. It is obvious that the nontribal communities of Kerala display a greater Dravidian influence, but traces of genetic admixture with the Mediterranean, western European, central Asian and East Asian populations can be observed. This characterizes the crypto-Dravidian features of the nontribal communities of Kerala. Demic diffusion of the local progressive communities with the migrant communities may have given rise to crypto-Dravidian features among the nontribal communities of Kerala. PMID:16948643

  9. Biosecurity interceptions of an invasive lizard: origin of stowaways and human-assisted spread within New Zealand

    PubMed Central

    Chapple, David G; Whitaker, Anthony H; Chapple, Stephanie N J; Miller, Kimberly A; Thompson, Michael B

    2013-01-01

    Globalization, and the resultant movement of animals beyond their native range, creates challenges for biosecurity agencies. Limited records of unintentional introductions inhibit our understanding of the trade pathways, transport vectors and mechanisms through which hitchhiker organisms are spread as stowaways. Here, we adopt a phylogeographic approach to determine the source and human-mediated dispersal pathways of New Zealand's only invasive lizard, the delicate skink (Lampropholis delicata), intercepted by biosecurity agencies in New Zealand. Biosecurity agencies correctly predicted the source region of 77% of stowaways, which were usually solitary adults, arriving via air or sea pathways during the cooler months, evading initial border checks and alive when detected. New arrivals from Australia comprised 16% of detections originating from the region between Brisbane and Sydney. Our analyses indicate human-mediated dispersal has driven the post-border spread of L. delicata within New Zealand. Propagule pressure was substantially greater for L. delicata compared with the noninvasive, congeneric Lampropholis guichenoti. Our results highlight the transport pathways, spread mechanisms, and stowaway characteristics of Lampropholis lizards entering New Zealand, which could enhance current biosecurity protocols and prevent the establishment of additional lizard species. PMID:23467589

  10. Epidemiology, phylogeny, and evolution of emerging enteric Picobirnaviruses of animal origin and their relationship to human strains.

    PubMed

    Malik, Yashpal S; Kumar, Naveen; Sharma, Kuldeep; Dhama, Kuldeep; Shabbir, Muhammad Zubair; Ganesh, Balasubramanian; Kobayashi, Nobumichi; Banyai, Krisztian

    2014-01-01

    Picobirnavirus (PBV) which has been included in the list of viruses causing enteric infection in animals is highly versatile because of its broad host range and genetic diversity. PBVs are among the most recent and emerging small, nonenveloped viruses with a bisegmented double-stranded RNA genome, classified under a new family "Picobirnaviridae." PBVs have also been detected from respiratory tract of pigs, but needs further close investigation for their inhabitant behavior. Though, accretion of genomic data of PBVs from different mammalian species resolved some of the ambiguity, quite a few questions and hypotheses regarding pathogenesis, persistence location, and evolution of PBVs remain unreciprocated. Evolutionary analysis reveals association of PBVs with partitiviruses especially fungi partitiviruses. Although, PBVs may have an ambiguous clinical implication, they do pose a potential public health concern in humans and control of PBVs mainly relies on nonvaccinal approach. Based upon the published data, from 1988 to date, generated from animal PBVs across the globe, this review provides information and discussion with respect to genetic analysis as well as evolution of PBVs of animal origin in relation to human strains. PMID:25136620

  11. Biosecurity interceptions of an invasive lizard: origin of stowaways and human-assisted spread within New Zealand.

    PubMed

    Chapple, David G; Whitaker, Anthony H; Chapple, Stephanie N J; Miller, Kimberly A; Thompson, Michael B

    2013-02-01

    Globalization, and the resultant movement of animals beyond their native range, creates challenges for biosecurity agencies. Limited records of unintentional introductions inhibit our understanding of the trade pathways, transport vectors and mechanisms through which hitchhiker organisms are spread as stowaways. Here, we adopt a phylogeographic approach to determine the source and human-mediated dispersal pathways of New Zealand's only invasive lizard, the delicate skink (Lampropholis delicata), intercepted by biosecurity agencies in New Zealand. Biosecurity agencies correctly predicted the source region of 77% of stowaways, which were usually solitary adults, arriving via air or sea pathways during the cooler months, evading initial border checks and alive when detected. New arrivals from Australia comprised 16% of detections originating from the region between Brisbane and Sydney. Our analyses indicate human-mediated dispersal has driven the post-border spread of L. delicata within New Zealand. Propagule pressure was substantially greater for L. delicata compared with the noninvasive, congeneric Lampropholis guichenoti. Our results highlight the transport pathways, spread mechanisms, and stowaway characteristics of Lampropholis lizards entering New Zealand, which could enhance current biosecurity protocols and prevent the establishment of additional lizard species. PMID:23467589

  12. Identification of the origin of adrenergic and cholinergic nerve fibers within the superior hypogastric plexus of the human fetus

    PubMed Central

    Zaitouna, Mazen; Alsaid, Bayan; Diallo, Djibril; Benoit, Gérard; Bessede, Thomas

    2013-01-01

    Nerve fibers contributing to the superior hypogastric plexus (SHP) and the hypogastric nerves (HN) are currently considered to comprise an adrenergic part of the autonomic nervous system located between vertebrae (T1 and L2), with cholinergic aspects originating from the second to fourth sacral spinal segments (S2, S3 and S4). The aim of this study was to identify the origin and the nature of the nerve fibers within the SHP and the HN, especially the cholinergic fibers, using computer-assisted anatomic dissection (CAAD). Serial histological sections were performed at the level of the lumbar spine and pelvis in five human fetuses between 14 and 30 weeks of gestation. Sections were treated with histological staining [hematoxylin-eosin (HE) and Masson's trichrome (TriM)] and with immunohistochemical methods to detect nerve fibers (anti-S100), adrenergic fibers (anti-TH), cholinergic fibers (anti-VAChT) and nitrergic fibers (anti-nNOS). The sections were then digitalized using a high-resolution scanner and the 3D images were reconstructed using winsurf software. These experiments revealed the coexistence of adrenergic and cholinergic fibers within the SHP and the HNs. One-third of these cholinergic fibers were nitrergic fibers [anti-VACHT (+)/anti-NOS (+)] and potentially pro-erectile, while the others were non-nitrergic [anti-VACHT (+)/anti-NOS (−)]. We found these cholinergic fibers arose from the lumbar nerve roots. This study described the nature of the SHP nerve fibers which gives a better understanding of the urinary and sexual dysfunctions after surgical injuries. PMID:23668336

  13. Eukaryotic origins.

    PubMed

    Lake, James A

    2015-09-26

    The origin of the eukaryotes is a fundamental scientific question that for over 30 years has generated a spirited debate between the competing Archaea (or three domains) tree and the eocyte tree. As eukaryotes ourselves, humans have a personal interest in our origins. Eukaryotes contain their defining organelle, the nucleus, after which they are named. They have a complex evolutionary history, over time acquiring multiple organelles, including mitochondria, chloroplasts, smooth and rough endoplasmic reticula, and other organelles all of which may hint at their origins. It is the evolutionary history of the nucleus and their other organelles that have intrigued molecular evolutionists, myself included, for the past 30 years and which continues to hold our interest as increasingly compelling evidence favours the eocyte tree. As with any orthodoxy, it takes time to embrace new concepts and techniques. PMID:26323753

  14. Eukaryotic origins

    PubMed Central

    Lake, James A.

    2015-01-01

    The origin of the eukaryotes is a fundamental scientific question that for over 30 years has generated a spirited debate between the competing Archaea (or three domains) tree and the eocyte tree. As eukaryotes ourselves, humans have a personal interest in our origins. Eukaryotes contain their defining organelle, the nucleus, after which they are named. They have a complex evolutionary history, over time acquiring multiple organelles, including mitochondria, chloroplasts, smooth and rough endoplasmic reticula, and other organelles all of which may hint at their origins. It is the evolutionary history of the nucleus and their other organelles that have intrigued molecular evolutionists, myself included, for the past 30 years and which continues to hold our interest as increasingly compelling evidence favours the eocyte tree. As with any orthodoxy, it takes time to embrace new concepts and techniques. PMID:26323753

  15. Adhesion of Human and Animal Escherichia coli Strains in Association with Their Virulence-Associated Genes and Phylogenetic Origins

    PubMed Central

    Frömmel, Ulrike; Lehmann, Werner; Rödiger, Stefan; Böhm, Alexander; Nitschke, Jörg; Weinreich, Jörg; Groß, Julia; Roggenbuck, Dirk; Zinke, Olaf; Ansorge, Hermann; Vogel, Steffen; Klemm, Per; Wex, Thomas; Schröder, Christian; Wieler, Lothar H.

    2013-01-01

    Intestinal colonization is influenced by the ability of the bacterium to inhabit a niche, which is based on the expression of colonization factors. Escherichia coli carries a broad range of virulence-associated genes (VAGs) which contribute to intestinal (inVAGs) and extraintestinal (exVAGs) infection. Moreover, initial evidence indicates that inVAGs and exVAGs support intestinal colonization. We developed new screening tools to genotypically and phenotypically characterize E. coli isolates originating in humans, domestic pigs, and 17 wild mammal and avian species. We analyzed 317 isolates for the occurrence of 44 VAGs using a novel multiplex PCR microbead assay (MPMA) and for adhesion to four epithelial cell lines using a new adhesion assay. We correlated data for the definition of new adhesion genes. inVAGs were identified only sporadically, particularly in roe deer (Capreolus capreolus) and the European hedgehog ( Erinaceus europaeus). The prevalence of exVAGs depended on isolation from a specific host. Human uropathogenic E. coli isolates carried exVAGs with the highest prevalence, followed by badger (Meles meles) and roe deer isolates. Adhesion was found to be very diverse. Adhesion was specific to cells, host, and tissue, though it was also unspecific. Occurrence of the following VAGs was associated with a higher rate of adhesion to one or more cell lines: afa-dra, daaD, tsh, vat, ibeA, fyuA, mat, sfa-foc, malX, pic, irp2, and papC. In summary, we established new screening methods which enabled us to characterize large numbers of E. coli isolates. We defined reservoirs for potential pathogenic E. coli. We also identified a very broad range of colonization strategies and defined potential new adhesion genes. PMID:23872574

  16. Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human population.

    PubMed

    Greenbaum, Jason A; Kotturi, Maya F; Kim, Yohan; Oseroff, Carla; Vaughan, Kerrie; Salimi, Nima; Vita, Randi; Ponomarenko, Julia; Scheuermann, Richard H; Sette, Alessandro; Peters, Bjoern

    2009-12-01

    A major concern about the ongoing swine-origin H1N1 influenza virus (S-OIV) outbreak is that the virus may be so different from seasonal H1N1 that little immune protection exists in the human population. In this study, we examined the molecular basis for pre-existing immunity against S-OIV, namely the recognition of viral immune epitopes by T cells or B cells/antibodies that have been previously primed by circulating influenza strains. Using data from the Immune Epitope Database, we found that only 31% (8/26) of B-cell epitopes present in recently circulating H1N1 strains are conserved in the S-OIV, with only 17% (1/6) conserved in the hemagglutinin (HA) and neuraminidase (NA) surface proteins. In contrast, 69% (54/78) of the epitopes recognized by CD8(+) T cells are completely invariant. We further demonstrate experimentally that some memory T-cell immunity against S-OIV is present in the adult population and that such memory is of similar magnitude as the pre-existing memory against seasonal H1N1 influenza. Because protection from infection is antibody mediated, a new vaccine based on the specific S-OIV HA and NA proteins is likely to be required to prevent infection. However, T cells are known to blunt disease severity. Therefore, the conservation of a large fraction of T-cell epitopes suggests that the severity of an S-OIV infection, as far as it is determined by susceptibility of the virus to immune attack, would not differ much from that of seasonal flu. These results are consistent with reports about disease incidence, severity, and mortality rates associated with human S-OIV. PMID:19918065

  17. Expression and regulation of the neural cell adhesion molecule L1 on human cells of myelomonocytic and lymphoid origin.

    PubMed

    Pancook, J D; Reisfeld, R A; Varki, N; Vitiello, A; Fox, R I; Montgomery, A M

    1997-05-01

    The neural cell adhesion molecule L1 has been implicated in a variety of neurologic processes, including neuritogenesis and cerebellar cell migration. Here we propose an expanded role for this cell adhesion molecule in the human immune system based on its expression on cells of myelomonocytic and lymphoid origin. Freshly isolated circulating monocytes had minimal L1 expression; however, activation of these effector cells by IFN-gamma, or as a result of density gradient isolation, resulted in a significant induction of L1 expression. Constitutive L1 expression was further evident on myelomonocytic cell lines but was absent on mature tissue macrophages. In further studies, positive selection with a L1-specific Ab enriched both B cells and dendritic precursor cells from peripheral blood. Significantly, L1 expression was not detected on mature dendritic cells but could be induced by treatment with LPS, PHA, and TNF-alpha. Immunohistochemical analysis further demonstrated significant L1 expression on follicular dendritic cells and on endothelial cells associated with the arterioles and red pulp of normal spleen. Based on these observations and known functions of L1, we propose that this cell adhesion molecule may contribute to cell-cell adhesion events associated with the effector function or extravasation of these immune effector cells. In support of the latter, we present evidence that L1 can be recognized by endothelial cells via the integrin alpha(v)beta3. PMID:9127006

  18. Human T-lymphotropic virus type 1 in coastal natives of British Columbia: phylogenetic affinities and possible origins.

    PubMed Central

    Picard, F J; Coulthart, M B; Oger, J; King, E E; Kim, S; Arp, J; Rice, G P; Dekaban, G A

    1995-01-01

    Human T-lymphotropic virus type 1 (HTLV-1) infection has been discovered recently in people of Amerindian descent living in coastal areas of British Columbia, Canada. DNA sequencing combined with phylogenetic analysis and restriction fragment length polymorphism (RFLP) typing of HTLV-1 strains recovered from these British Columbia Indians (BCI) was conducted. Sequence-based phylogenetic trees distributed the BCI isolates among the Japanese subcluster (subcluster B) and the geographically widely distributed subcluster (subcluster A) of the large HTLV-1 cosmopolitan cluster. Long terminal repeat (LTR) RFLP typing revealed three distinct, equally frequent LTR cleavage patterns, two of which were of previously recognized Japanese and widely dispersed cosmopolitan types. A third, new cleavage pattern was detected which may have arisen by recombination between two other HTLV-1 genotypes. Our results suggest multiple origins for HTLV-1 in BCI, which are equally consistent with (i) a cluster of recent sporadic infections, (ii) ancient endemic vertical transmission through Amerindian lineages, or (iii) both. PMID:7474147

  19. HPLC analysis of the novel antidepressant duloxetine in human plasma after an original solid-phase extraction procedure.

    PubMed

    Mercolini, Laura; Mandrioli, Roberto; Cazzolla, Roberto; Amore, Mario; Raggi, Maria Augusta

    2007-09-01

    Duloxetine is the most recent serotonin and norepinephrine reuptake inhibitor (SNRI) drug introduced for the therapy of depression. Thus, it is evident that there is a need for having on hand new reliable analytical methods for the determination of duloxetine plasma levels in depressed patients. The present paper deals with the development of a rapid and sensitive high-performance liquid chromatographic method for duloxetine analysis in human plasma. The assays were carried out using a C8 reversed-phase column and a mobile phase composed of 60% aqueous phosphate buffer containing triethylamine at pH 3.0 and 40% acetonitrile. The UV detector was set at 230 nm and loxapine was used as the internal standard. An original pre-treatment of plasma samples was developed, based on solid-phase extraction (SPE) with mixed-mode reversed phase-strong cation exchange cartridges (30 mg, 1 mL). The extraction yields values were higher than 90%. Linearity was found in the 2-200 ng mL(-1) duloxetine concentration range; the limit of quantitation was 2.0 ng mL(-1) and the limit of detection was 0.7 ng mL(-1). The method was applied to plasma samples from depressed patients undergoing therapy with duloxetine. Precision data and accuracy results were satisfactory and no interference from other drugs was found. Thus, the method seems to be suitable for the therapeutic drug monitoring of duloxetine in depressed patients' plasma. PMID:17572161

  20. Osteogenic Potential of Human Oral-Periosteal Cells (PCs) Isolated From Different Oral Origin: An In Vitro Study.

    PubMed

    Ceccarelli, Gabriele; Graziano, Antonio; Benedetti, Laura; Imbriani, Marcello; Romano, Federica; Ferrarotti, Francesco; Aimetti, Mario; Cusella de Angelis, Gabriella M

    2016-03-01

    The periosteum is a specialized connective tissue containing multipotent stem cells capable of bone formation. In this study, we aimed at demonstrating that human oral periosteal cells derived from three different oral sites (upper vestibule, lower vestibule, and hard palate) represent an innovative cell source for maxillo-facial tissue engineering applications in terms of accessibility and self-commitment towards osteogenic lineage. Periosteal cells (PCs) were isolated from patients with different ages (20-30 yy, 40-50 yy, 50-60 yy); we then analyzed the in vitro proliferation capacity and the bone self-commitment of cell clones culturing them without any osteogenic supplement to support their differentiation. We found that oral PCs, independently of their origin and age of patients, are mesenchymal stem cells with stem cell characteristics (clonogenical and proliferative activity) and that, even in absence of any osteogenic induction, they undertake the osteoblast lineage after 45 days of culture. These results suggest that oral periosteal cells could replace mesenchymal cells from bone marrow in oral tissue-engineering applications. PMID:26206324

  1. U.S. Human Immunodeficiency Virus Type 1 Epidemic: Date of Origin, Population History, and Characterization of Early Strains

    PubMed Central

    Robbins, Kenneth E.; Lemey, Philippe; Pybus, Oliver G.; Jaffe, Harold W.; Youngpairoj, Ae S.; Brown, Teresa M.; Salemi, Marco; Vandamme, Anne-Mieke; Kalish, Marcia L.

    2003-01-01

    Human immunodeficiency virus (HIV) type 1 subtype B sequences (whole envelope and the p17 region of gag) were obtained from peripheral blood mononuclear cell samples collected in 1981 from seven HIV-infected U.S. individuals and in 1982 from one infected Canadian resident. Phylogenetic and nucleotide distance analyses were performed by using database sequences representing North American strains collected from 1978 to 1995. The estimated phylogeny was starlike, with early strains represented on different lineages. When sequences were grouped by years of collection, nucleotide distance comparisons demonstrated an increase in diversity over time and indicated that contemporary strains are more closely related to early epidemic strains than to each other. Using a recently developed likelihood ratio reduction procedure, the date of origin of the U.S. epidemic was estimated to be 1968 1.4 years. A coalescent approach was also used to estimate the population history of the U.S. subtype B epidemic. Our analyses provide new information that implies an exponential growth rate from the beginning of the U.S. HIV epidemic. The dating results suggest a U.S. introduction date (or date of divergence from the most recent common ancestor) that precedes the date of the earliest known AIDS cases in the late 1970s. Furthermore, the estimated epidemic growth curve shows a period of exponential growth that preceded most of the early documented cases and also indicates a leveling of prevalence rates in the recent past. PMID:12743293

  2. A modern human humerus from the early aurignacian of Vogelherdhöhle (Stetten, Germany).

    PubMed

    Churchill, S E; Smith, F H

    2000-06-01

    Implicit in much of the discussion of the cultural and population biological dynamics of modern human origins in Europe is the assumption that the Aurignacian, from its very start, was made by fully modern humans. The veracity of this assumption has been challenged in recent years by the association of Neandertal skeletal remains with a possibly Aurignacian assemblage at Vindija Cave (Croatia) and the association of Neandertals with distinctly Upper Paleolithic (but non-Aurignacian) assemblages at Arcy-sur-Cure and St. C¿esaire (France). Ideally we need human fossil material that can be confidently assigned to the early Aurignacian to resolve this issue, yet in reality there is a paucity of well-provenanced human fossils from early Upper Paleolithic contexts. One specimen, a right humerus from the site of Vogelherd (Germany), has been argued, based on its size, robusticity, and muscularity, to possibly represent a Neandertal in an Aurignacian context. The morphological affinities of the Vogelherd humerus were explored by univariate and multivariate comparisons of humeral epiphyseal and diaphyseal shape and strength measures relative to humeri of Neandertals and Early Upper Paleolithic (later Aurignacian and Gravettian) modern humans. On the basis of diaphyseal cross-sectional geometry, deltoid tuberosity morphology, and distal epiphyseal morphology, the specimen falls clearly and consistently with European early modern humans and not with Neandertals. Along with the other Vogelherd human remains, the Vogelherd humerus represents an unequivocal association between the Aurignacian and modern human morphology in Europe. PMID:10813706

  3. A Set of Novel Monoclonal Antibodies Against Swine-Origin Pandemic H1N1 Differentiate Swine H1N1 and Human Seasonal H1N1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In April 2009, a novel H1N1 influenza virus (S-OIV) emerged in North America and caused the first influenza pandemic of the 21st century. The new pandemic strain is a triple reassortant influenza virus of swine origin containing genes from avian, swine and human influenza viruses. It is genetically ...

  4. Glycan analysis of Fonsecaea monophora from clinical and environmental origins reveals different structural profile and human antigenic response

    PubMed Central

    Burjack, Juliana R.; Santana-Filho, Arquimedes P.; Ruthes, Andrea C.; Riter, Daniel S.; Vicente, Vania A.; Alvarenga, Larissa M.; Sassaki, Guilherme L.

    2014-01-01

    Dematiaceous fungi constitute a large and heterogeneous group, characterized by having a dark pigment, the dihydroxynaftalen melanin—DHN, inside their cell walls. In nature they are found mainly as soil microbiota or decomposing organic matter, and are spread in tropical and subtropical regions. The fungus Fonsecaea monophora causes chromoblastomycosis in humans, and possesses essential mechanisms that may enhance pathogenicity, proliferation and dissemination inside the host. Glycoconjugates confer important properties to these pathogenic microorganisms. In this work, structural characterization of glycan structures present in two different strains of F. monophora MMHC82 and FE5p4, from clinical and environmental origins, respectively, was performed. Each one were grown on Minimal Medium (MM) and Czapeck-Dox (CD) medium, and the water soluble cell wall glycoconjugates and exopolysaccharides (EPS) were evaluated by NMR, methylation and principal component analysis (PCA). By combining the methylation and 2D NMR analyses, it was possible to visualize the glycosidic profiles of the complex carbohydrate mixtures. Significant differences were observed in β-D-Galf-(1→5) and (1→6) linkages, α- and β-D-Glcp-(1→3), (1→4), and (1→6) units, as well as in α-D-Manp. PCA from 1H-NMR data showed that MMHC82 from CD medium showed a higher variation in the cell wall carbohydrates, mainly related to O-2 substituted β-D-Galf (δ 106.0/5.23 and δ 105.3/5.23) units. In order to investigate the antigenic response of the glycoconjugates, these were screened against serum from chromoblastomycosis patients. The antigen which contained the cell wall of MMHC82 grown in MM had β-D-Manp units that promoted higher antigenic response. The distribution of these fungal species in nature and the knowledge of how cell wall polysaccharides and glycoconjugates structure vary, may contribute to the better understanding and the elucidation of the pathology caused by this fungus. PMID:25401093

  5. Evolution of influenza A virus nucleoprotein genes: implications for the origins of H1N1 human and classical swine viruses.

    PubMed Central

    Gorman, O T; Bean, W J; Kawaoka, Y; Donatelli, I; Guo, Y J; Webster, R G

    1991-01-01

    A phylogenetic analysis of 52 published and 37 new nucleoprotein (NP) gene sequences addressed the evolution and origin of human and swine influenza A viruses. H1N1 human and classical swine viruses (i.e., those related to Swine/Iowa/15/30) share a single common ancestor, which was estimated to have occurred in 1912 to 1913. From this common ancestor, human and classical swine virus NP genes have evolved at similar rates that are higher than in avian virus NP genes (3.31 to 3.41 versus 1.90 nucleotide changes per year). At the protein level, human virus NPs have evolved twice as fast as classical swine virus NPs (0.66 versus 0.34 amino acid change per year). Despite evidence of frequent interspecies transmission of human and classical swine viruses, our analysis indicates that these viruses have evolved independently since well before the first isolates in the early 1930s. Although our analysis cannot reveal the original host, the ancestor virus was avianlike, showing only five amino acid differences from the root of the avian virus NP lineage. The common pattern of relationship and origin for the NP and other genes of H1N1 human and classical swine viruses suggests that the common ancestor was an avian virus and not a reassortant derived from previous human or swine influenza A viruses. The new avianlike H1N1 swine viruses in Europe may provide a model for the evolution of newly introduced avian viruses into the swine host reservoir. The NPs of these viruses are evolving more rapidly than those of human or classical swine viruses (4.50 nucleotide changes and 0.74 amino acid change per year), and when these rates are applied to pre-1930s human and classical swine virus NPs, the predicted date of a common ancestor is 1918 rather than 1912 to 1913. Thus, our NP phylogeny is consistent with historical records and the proposal that a short time before 1918, a new H1N1 avianlike virus entered human or swine hosts (O. T. Gorman, R. O. Donis, Y. Kawaoka, and R. G. Webster, J. Virol. 64:4893-4902, 1990). This virus provided the ancestors of all known human influenza A virus genes, except for HA, NA, and PB1, which have since been reassorted from avian viruses. We propose that during 1918 a virulent strain of this new avianlike virus caused a severe human influenza pandemic and that the pandemic virus was introduced into North American swine populations, constituting the origin of classical swine virus. PMID:2041090

  6. Human Origins: Problems in the Interpretation of New Evidence. Third Edition. AAAS Study Guides on Contemporary Problems.

    ERIC Educational Resources Information Center

    Almquist, Alan J.; Cronin, John E.

    This Chautauqua-type short course in human evolution is divided into two parts: The Biochemical Evidence for Human Evolution, and the Fossil Evidence for Human Evolution. The first part covers the comparison of macromolecular differences between species. This includes comparison of DNA base-ratios and amino acid substitution in enzymes and other…

  7. Time and Place of Human Origins, the African Eve Hypothesis Examined through Modelling: Can High Schools Contribute?

    ERIC Educational Resources Information Center

    Oxnard, Charles

    1994-01-01

    Studies of mitochondrial DNA imply that modern humans arose in Africa 150,000 years ago and spread throughout the world, replacing all prior human groups. But many paleontologists see continuity in human fossils on each continent and over a much longer time. Modeling may help test these alternatives. (Author/MKR)

  8. RecQL4 is required for the association of Mcm10 and Ctf4 with replication origins in human cells

    PubMed Central

    Im, Jun-Sub; Park, Soon-Young; Cho, Won-Ho; Bae, Sung-Ho; Hurwitz, Jerard; Lee, Joon-Kyu

    2015-01-01

    Though RecQL4 was shown to be essential for the initiation of DNA replication in mammalian cells, its role in initiation is poorly understood. Here, we show that RecQL4 is required for the origin binding of Mcm10 and Ctf4, and their physical interactions and association with replication origins are controlled by the concerted action of both CDK and DDK activities. Although RecQL4-dependent binding of Mcm10 and Ctf4 to chromatin can occur in the absence of pre-replicative complex, their association with replication origins requires the presence of the pre-replicative complex and CDK and DDK activities. Their association with replication origins and physical interactions are also targets of the DNA damage checkpoint pathways which prevent initiation of DNA replication at replication origins. Taken together, the RecQL4-dependent association of Mcm10 and Ctf4 with replication origins appears to be the first important step controlled by S phase promoting kinases and checkpoint pathways for the initiation of DNA replication in human cells. PMID:25602958

  9. Differentiation between Streptococcus gallolyticus Strains of Human Clinical and Veterinary Origins and Streptococcus bovis Strains from the Intestinal Tracts of Ruminants

    PubMed Central

    Devriese, Luc A.; Vandamme, Peter; Pot, Bruno; Vanrobaeys, Mia; Kersters, Karel; Haesebrouck, Freddy

    1998-01-01

    Strains formerly identified as Streptococcus bovis were allotted to two groups by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of whole-cell proteins. Strains from humans with infections, mostly patients with endocarditis, and strains from pigeons with septicemia clustered with the recently described species Streptococcus gallolyticus. The original S. bovis type strain and strains exclusively from ruminants formed the second cluster. The findings indicate that S. gallolyticus is more likely to be involved in human and animal infections than S. bovis. Growth characteristics and several biochemical reactions were found to be useful in the differentiation of S. gallolyticus from S. bovis. PMID:9817865

  10. First Ancient Mitochondrial Human Genome from a Prepastoralist Southern African

    PubMed Central

    Smith, Andrew B.; Hayes, Vanessa M.

    2014-01-01

    The oldest contemporary human mitochondrial lineages arose in Africa. The earliest divergent extant maternal offshoot, namely haplogroup L0d, is represented by click-speaking forager peoples of southern Africa. Broadly defined as Khoesan, contemporary Khoesan are today largely restricted to the semidesert regions of Namibia and Botswana, whereas archeological, historical, and genetic evidence promotes a once broader southerly dispersal of click-speaking peoples including southward migrating pastoralists and indigenous marine-foragers. No genetic data have been recovered from the indigenous peoples that once sustained life along the southern coastal waters of Africa prepastoral arrival. In this study we generate a complete mitochondrial genome from a 2,330-year-old male skeleton, confirmed through osteological and archeological analysis as practicing a marine-based forager existence. The ancient mtDNA represents a new L0d2c lineage (L0d2c1c) that is today, unlike its Khoe-language based sister-clades (L0d2c1a and L0d2c1b) most closely related to contemporary indigenous San-speakers (specifically Ju). Providing the first genomic evidence that prepastoral Southern African marine foragers carried the earliest diverged maternal modern human lineages, this study emphasizes the significance of Southern African archeological remains in defining early modern human origins. PMID:25212860

  11. First ancient mitochondrial human genome from a prepastoralist southern African.

    PubMed

    Morris, Alan G; Heinze, Anja; Chan, Eva K F; Smith, Andrew B; Hayes, Vanessa M

    2014-10-01

    The oldest contemporary human mitochondrial lineages arose in Africa. The earliest divergent extant maternal offshoot, namely haplogroup L0d, is represented by click-speaking forager peoples of southern Africa. Broadly defined as Khoesan, contemporary Khoesan are today largely restricted to the semidesert regions of Namibia and Botswana, whereas archeological, historical, and genetic evidence promotes a once broader southerly dispersal of click-speaking peoples including southward migrating pastoralists and indigenous marine-foragers. No genetic data have been recovered from the indigenous peoples that once sustained life along the southern coastal waters of Africa prepastoral arrival. In this study we generate a complete mitochondrial genome from a 2,330-year-old male skeleton, confirmed through osteological and archeological analysis as practicing a marine-based forager existence. The ancient mtDNA represents a new L0d2c lineage (L0d2c1c) that is today, unlike its Khoe-language based sister-clades (L0d2c1a and L0d2c1b) most closely related to contemporary indigenous San-speakers (specifically Ju). Providing the first genomic evidence that prepastoral Southern African marine foragers carried the earliest diverged maternal modern human lineages, this study emphasizes the significance of Southern African archeological remains in defining early modern human origins. PMID:25212860

  12. c-ETS transcription factors play an essential role in the licensing of human MCM4 origin of replication.

    PubMed

    Sidhu, Kaveri; Kumar, Vijay

    2015-11-01

    In metazoans, DNA replication is a highly regulated and ordered process that occurs during the S phase of cell cycle. It begins with the licensing of origins of replication usually found in close proximity of actively transcribing genes owing perhaps to a profound influence of transcription factors on the epigenetic signatures and architecture of chromatin. Here we show that ETS transcription factors are novel regulators of MCM4 origin, whose binding sites are localized between two divergently transcribing MCM4 and PRKDC genes. c-ETS1 and c-ETS2 were recruited to the MCM4 origin respectively during the S and G1 phases of cell cycle. c-ETS2 binding was facilitated by an active chromatin distinguished by acetylated histone H3 orchestrated by histone acetyl transferase GCN5 and followed by HBO1 mediated histone H4 acetylation. Interestingly, c-ETS2 overexpression led to increased BrdU incorporation in the S phase cells while its down-regulation by RNA interference compromised the loading of pre-replicative complex at the origin. Conversely, the recruitment of c-ETS1 at the origin coincided with histone H3 methylation signature characteristic of closed chromatin conformation. As expected, enforced expression of c-ETS1 severely compromised DNA replication whereas its down-regulation enhanced DNA replication as evident from increased BrdU incorporation. Thus, c-ETS transcription factors appear to be key regulators of MCM4 origin where c-ETS2 seems to promote DNA replication whereas c-ETS1 functions as a negative regulator. PMID:26365772

  13. CROSS-SPECIES TRANSMISSION OF GIARDIA: INOCULATION OF BEAVERS AND MUSKRATS WITH CYSTS OF HUMAN, BEAVER, MOUSE, AND MUSKRAT ORIGIN

    EPA Science Inventory

    Giardia cysts isolated from humans, beavers, mice and muskrats were tested in cross-species transmission experiments for their ability to infect either beavers or muskrats. iardia cysts, derived from multiple symptomatic human donors and used for inoculation of beavers ormuskrats...

  14. "The city of Hepar": rituals, gastronomy, and politics at the origins of the modern names for the liver.

    PubMed

    Riva, Michele Augusto; Riva, Enrica; Spicci, Mauro; Strazzabosco, Mario; Giovannini, Marcello; Cesana, Giancarlo

    2011-11-01

    Medical etymology sometimes provides unexpected information about health concepts and medical practice in different times and cultures. We conducted an etymological analysis of the terms used to indicate "liver" in Germanic and Romance languages. The Greek word "hèpar" was originally connected to the concept of "pleasure", showing that in antiquity the liver was considered to be the seat of soul and human feelings. In Romance languages, the Latin term "ficatum" was linked to the ancient practice of fattening geese with figs (ficus in Latin) to make their livers more delicious. This relationship between the liver, fat, and carbohydrates seems to indicate that ancient gourmets had clear knowledge of the nutritional mechanisms underlying "fatty liver" in animals. On the other hand, the Germanic term "lifere" was initially connected to "life", underscoring the relation of the liver to health and existence. In the Early Modern Age, the liver became a recurring image in political reflection, especially within the Elizabethan tradition of the body politic, where the king was frequently described as the "liver" of his country. Finally, the liver was used to indicate courage, or the lack of it: some modern French and English idiomatic expressions derive from the ancient belief that people who had no blood in their liver ("lily-livered") would thus be cowards or betrayers. PMID:21718666

  15. “The city of Hepar”: Rituals, gastronomy, and politics at the origins of the modern names for the liver

    PubMed Central

    Riva, Michele Augusto; Riva, Enrica; Spicci, Mauro; Strazzabosco, Mario; Giovannini, Marcello; Cesana, Giancarlo

    2013-01-01

    Summary Medical etymology sometimes provides unexpected information about health concepts and medical practice in different times and cultures. We conducted an etymological analysis of the terms used to indicate “liver” in Germanic and Romance languages. The Greek word “hèpar” was originally connected to the concept of “pleasure”, showing that in antiquity the liver was considered to be the seat of soul and human feelings. In Romance languages, the Latin term “ficatum” was linked to the ancient practice of fattening geese with figs (ficus in Latin) to make their livers more delicious. This relationship between the liver, fat, and carbohydrates seems to indicate that ancient gourmets had clear knowledge of the nutritional mechanisms underlying “fatty liver” in animals. On the other hand, the Germanic term “lifere” was initially connected to “life”, underscoring the relation of the liver to health and existence. In the Early Modern Age, the liver became a recurring image in political reflection, especially within the Elizabethan tradition of the body politic, where the king was frequently described as the “liver” of his country. Finally, the liver was used to indicate courage, or the lack of it: some modern French and English idiomatic expressions derive from the ancient belief that people who had no blood in their liver (“lily-livered”) would thus be cowards or betrayers. PMID:21718666

  16. Two E2 binding sites alone are sufficient to function as the minimal origin of replication of human papillomavirus type 18 DNA.

    PubMed

    Sverdrup, F; Khan, S A

    1995-02-01

    Replication of papillomaviruses requires an origin of replication and two virus-encoded proteins, E1 and E2. Using a transient replication assay for human papillomavirus type 18 (HPV-18) DNA, we have found that two adjacent sequences present within the origin of replication can independently support replication. The first, a 77-bp region, contains one E2 binding site (E2BS) and a 16-bp inverted repeat element that probably corresponds to the E1 binding site (E1BS). The other, an 81-bp region, includes two E2BS but lacks the putative E1BS. A synthetic 33-bp oligonucleotide containing two high-affinity E2BS was also found to function as an origin of replication. Replication of all these plasmids was absolutely dependent on the presence of the HPV-18 E1 and E2 proteins. The HPV-1a E1 and E2 proteins were also found to support replication of a plasmid containing the complete HPV-18 origin but failed to replicate a plasmid containing two E2BS alone. Our results suggest that the E2 protein can target E1 to the origin through the formation of an E1-E2 complex which is likely to be involved the initiation of replication. PMID:7815514

  17. The human oncoprotein MDM2 induces replication stress eliciting early intra-S-phase checkpoint response and inhibition of DNA replication origin firing.

    PubMed

    Frum, Rebecca A; Singh, Shilpa; Vaughan, Catherine; Mukhopadhyay, Nitai D; Grossman, Steven R; Windle, Brad; Deb, Sumitra; Deb, Swati Palit

    2014-01-01

    Conventional paradigm ascribes the cell proliferative function of the human oncoprotein mouse double minute2 (MDM2) primarily to its ability to degrade p53. Here we report that in the absence of p53, MDM2 induces replication stress eliciting an early S-phase checkpoint response to inhibit further firing of DNA replication origins. Partially synchronized lung cells cultured from p53-/-:MDM2 transgenic mice enter S phase and induce S-phase checkpoint response earlier than lung cells from p53-/- mice and inhibit firing of DNA replication origins. MDM2 activates chk1 phosphorylation, elevates mixed lineage lymphoma histone methyl transferase levels and promotes checkpoint-dependent tri-methylation of histone H3 at lysine 4, known to prevent firing of late replication origins at the early S phase. In the absence of p53, a condition that disables inhibition of cyclin A expression by MDM2, MDM2 increases expression of cyclin D2 and A and hastens S-phase entry of cells. Consistently, inhibition of cyclin-dependent kinases, known to activate DNA replication origins during firing, inhibits MDM2-mediated induction of chk1 phosphorylation indicating the requirement of this activity in MDM2-mediated chk1 phosphorylation. Our data reveal a novel pathway, defended by the intra-S-phase checkpoint, by which MDM2 induces unscheduled origin firing and accelerates S-phase entry of cells in the absence of p53. PMID:24163099

  18. Characterization of Staphylococcus aureus from Humans and a Comparison with İsolates of Animal Origin, in North Dakota, United States.

    PubMed

    Velasco, Valeria; Buyukcangaz, Esra; Sherwood, Julie S; Stepan, Ryan M; Koslofsky, Ryan J; Logue, Catherine M

    2015-01-01

    Different clones of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus have been found in humans as well as in animals and retail meat. However, more information about the genetic characteristics and similarities between strains is needed. The aim of this study was to identify and characterize Staphylococcus aureus from humans, and to compare their characteristics with isolates of animal origin. A total of 550 nasal swabs were taken from healthy humans, and S. aureus was isolated and identified. Positive S. aureus isolates were subjected to molecular typing and susceptibility testing. In addition, 108 MRSA isolates recovered from clinical patients in the state of North Dakota and 133 S. aureus isolates from animals and meat previously analyzed were included. The nasal carriage of S. aureus in healthy people was 7.6% and, in general, clones were genetically diverse. None of the S. aureus strains obtained from healthy people were mecA- or PVL-positive. A total of 105 (97.2%) MRSA isolates from clinical cases harbored the mecA gene and 11 (10.2%) isolated from blood stream infections harbored the PVL gene. The most common resistance profile among S. aureus from healthy people was penicillin, and from clinical cases were erythromycin-penicillin-ciprofloxacin. The rate of multidrug resistance (MDR) was 70% in humans. Most of the S. aureus harboring mecA and PVL genes were identified as ST5 and ST8, and exhibited MDR. However, S. aureus isolates of animal origin used for comparison exhibited a lower rate of MDR. The most common resistance profiles in isolates of animal origin were penicillin-tetracycline and penicillin-tetracycline-erythromycin, in animals and raw meat, respectively. The ST5 was also found in animals and meat, with ST9 and ST398 being the major clones. The genetic similarity between clones from humans and meat suggests the risk of spread of S. aureus in the food chain. PMID:26484768

  19. Characterization of Staphylococcus aureus from Humans and a Comparison with İsolates of Animal Origin, in North Dakota, United States

    PubMed Central

    Velasco, Valeria; Buyukcangaz, Esra; Sherwood, Julie S.; Stepan, Ryan M.; Koslofsky, Ryan J.; Logue, Catherine M.

    2015-01-01

    Different clones of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus have been found in humans as well as in animals and retail meat. However, more information about the genetic characteristics and similarities between strains is needed. The aim of this study was to identify and characterize Staphylococcus aureus from humans, and to compare their characteristics with isolates of animal origin. A total of 550 nasal swabs were taken from healthy humans, and S. aureus was isolated and identified. Positive S. aureus isolates were subjected to molecular typing and susceptibility testing. In addition, 108 MRSA isolates recovered from clinical patients in the state of North Dakota and 133 S. aureus isolates from animals and meat previously analyzed were included. The nasal carriage of S. aureus in healthy people was 7.6% and, in general, clones were genetically diverse. None of the S. aureus strains obtained from healthy people were mecA- or PVL-positive. A total of 105 (97.2%) MRSA isolates from clinical cases harbored the mecA gene and 11 (10.2%) isolated from blood stream infections harbored the PVL gene. The most common resistance profile among S. aureus from healthy people was penicillin, and from clinical cases were erythromycin-penicillin-ciprofloxacin. The rate of multidrug resistance (MDR) was 70% in humans. Most of the S. aureus harboring mecA and PVL genes were identified as ST5 and ST8, and exhibited MDR. However, S. aureus isolates of animal origin used for comparison exhibited a lower rate of MDR. The most common resistance profiles in isolates of animal origin were penicillin-tetracycline and penicillin-tetracycline-erythromycin, in animals and raw meat, respectively. The ST5 was also found in animals and meat, with ST9 and ST398 being the major clones. The genetic similarity between clones from humans and meat suggests the risk of spread of S. aureus in the food chain. PMID:26484768

  20. Risk Factors for Human Salmonellosis Originating from Pigs, Cattle, Broiler Chickens and Egg Laying Hens: A Combined Case-Control and Source Attribution Analysis

    PubMed Central

    Mughini-Gras, Lapo; Enserink, Remko; Friesema, Ingrid; Heck, Max; van Duynhoven, Yvonne; van Pelt, Wilfrid

    2014-01-01

    Several case-control studies have investigated risk factors for human salmonellosis while others have used Salmonella subtyping to attribute human infections to different food and animal reservoirs. This study combined case-control and source attribution data into a single analysis to explore risk factors at the point of exposure for human salmonellosis originating from four putative food-producing animal reservoirs (pigs, cattle, broilers and layers/eggs) in the Netherlands. We confirmed that most human cases (∼90%) were attributable to layers/eggs and pigs. Layers/eggs and broilers were the most likely reservoirs of salmonellosis in adults, in urban areas, and in spring/summer, whereas pigs and cattle were the most likely reservoirs of salmonellosis in children, in rural areas, and in autumn/winter. Several reservoir-specific risk factors were identified. Not using a chopping board for raw meat only and consuming raw/undercooked meat were risk factors for infection with salmonellas originating from pigs, cattle and broilers. Consuming raw/undercooked eggs and by-products were risk factors for layer/egg-associated salmonellosis. Using antibiotics was a risk factor for pig- and cattle-associated salmonellosis and using proton-pump inhibitors for salmonellosis attributable to any reservoir. Pig- and cattle-associated infections were also linked to direct contact with animals and environmental exposure (e.g. playing in sandboxes). Eating fish, meat in pastry, and several non-meat foods (fruit, vegetables and pasteurized dairy products) were protective factors. Consuming pork and occupational exposure to animals and/or raw meats were protective against layer/egg-associated salmonellosis. We concluded that individuals acquiring salmonellosis from different reservoirs have different associated risk factors, suggesting that salmonellas may infect humans through various transmission pathways depending on their original reservoirs. The outcome of classical case-control studies can be enhanced by incorporating source attribution data and vice versa. PMID:24503703

  1. Human BK Polyomavirus Plasmid pBKV (34-2) (Dunlop) Contains Mutations Not Found in the Originally Published Sequences

    PubMed Central

    Henriksen, Stian; Mittelholzer, Christian; Gosert, Rainer; Hirsch, Hans H.

    2015-01-01

    The plasmid pBKV (34-2) (ATCC 45025) contains the entire BK polyomavirus Dunlop genome. Sequencing revealed 12 point mutations compared to the GenBank sequence, but only 4 point mutations compared to the published sequence. The origin of these differences is unknown, but may impact virological as well as diagnostic research and development. PMID:25814590

  2. Human Bertiella studeri (family Anoplocephalidae) infection of probable Southeast Asian origin in Mauritian children and an adult.

    PubMed

    Bhagwant, S

    2004-02-01

    Morphologic studies on preserved and recently collected Bertiella specimens obtained from Mauritian children and an adult indicate that human infection is caused by Bertiella studeri instead of B. mucronata. This cestode might have been accidentally introduced onto the island of Mauritius from the Southeast Asia along with monkeys in the 17th century. We present information that will help identify B. studeri and provide a correct diagnosis. The case reports indicate gastrointestinal disturbances in human bertiellosis. Human infection with Bertiella studeri is reported for the first time in a Mauritian adult. PMID:14993637

  3. The origins of human gene mapping. With particular reference to the contributions of J. B. S. Haldane.

    PubMed

    Dronamraju, K R

    1987-11-01

    Methods in human gene mapping, including those developed by Bell and Haldane, Morton, and the more recent ones using somatic cell fusion, restriction fragment length polymorphism (RFLP), and multipoint linkage, are briefly reviewed. PMID:3328738

  4. Genome Sequence of a Circulating Human-Like Swine-Origin Influenza A Virus H3N2 Strain.

    PubMed

    Li, Xinsheng; Wang, Junya; Chen, Hong-Ying; Yan, Ruoqian; Du, Xiangdang

    2013-01-01

    The full-genome sequence of A/swine/Henan/1/2010, a strain of influenza A virus isolated in central China, was determined. Phylogenetic analyses show that its eight genomic segments are human-like, and some of its segments have appeared in swine H1N2, swine H1N1, and human H1N2 influenza viruses. PMID:24233586

  5. Evaluation of the efficacy of 100% Type-I collagen membrane of bovine origin in the treatment of human gingival recession: A clinical study

    PubMed Central

    Soni, Nitin; Sikri, Poonam; Kapoor, Daljit; Soni, Bhavita Wadhwa; Jain, Rachna

    2014-01-01

    Background: Various treatment modalities have been devised for gingival recession, which is one of the most common signs of periodontal disease. The present study evaluates the efficacy of bioresorbable 100% type I collagen membrane of bovine origin in the treatment of human gingival recession. Materials and Methods: Twenty cases of Miller's class I or class II localized gingival recession defects on the facial surface were treated with 100% type I collagen membrane of bovine origin in conjunction with coronally positioned flap. Pre-operative and post-operative assessments were performed with respect to probing pocket depth, clinical attachment level and clinical recession at 12, 24 and 36 weeks. The data thus collected were analyzed statistically. Results: Statistically significant improvement based on Student's t test was found in all the three clinical parameters. Conclusion: Bioresorbable 100% type I collagen membrane of bovine origin has given inspiring results in the treatment of human gingival recession defects, thereby justifying the use of this material wherever indicated. PMID:25565742

  6. Differential Induction of Type I and Type III Interferons by Swine and Human Origin H1N1 Influenza A Viruses in Porcine Airway Epithelial Cells

    PubMed Central

    Krishna, Venkatramana D.; Roach, Erin; Zaidman, Nathan A.; Panoskaltsis-Mortari, Angela; Rotschafer, Jessica H.; O’Grady, Scott M.; Cheeran, Maxim C-J.

    2015-01-01

    Interferons (IFNs) have been shown to inhibit influenza A virus (IAV) replication and play an essential role in controlling viral infection. Here we studied the kinetics and magnitude of induction of type I and type III IFN transcripts by primary porcine airway epithelial cells (pAECs) in response to swine and human origin IAV. We observed that swine influenza viruses (SIV) replicate more efficiently than the human pandemic influenza A/California/2009 (pH1N1 CA/09) in pAECs. Interestingly, we also found significant difference in kinetics of IFN-β, IFN-λ1 and IFN-λ3 gene expression by these viruses. While there was delay of up to 12 hours post infection (h p.i.) in induction of IFN genes in pAECs infected with swine IAV A/Sw/Illinois/2008 (H1N1 IL/08), human pH1N1 CA/09 rapidly induced IFN-β, IFN-λ1 and IFN-λ3 gene expression as early as 4 h p.i. However, the magnitude of IFN-β and IFN-λ3 induction at 24 h p.i. was not significantly different between the viral strains tested. Additionally, we found that swine H1N1 IL/08 was less sensitive to dsRNA induced antiviral response compared to human pH1N1 CA/09. Our data suggest that the human and swine IAVs differ in their ability to induce and respond to type I and type III interferons in swine cells. Swine origin IAV may have adapted to the pig host by subverting innate antiviral responses to viral infection. PMID:26384331

  7. Differential Induction of Type I and Type III Interferons by Swine and Human Origin H1N1 Influenza A Viruses in Porcine Airway Epithelial Cells.

    PubMed

    Krishna, Venkatramana D; Roach, Erin; Zaidman, Nathan A; Panoskaltsis-Mortari, Angela; Rotschafer, Jessica H; O'Grady, Scott M; Cheeran, Maxim C-J

    2015-01-01

    Interferons (IFNs) have been shown to inhibit influenza A virus (IAV) replication and play an essential role in controlling viral infection. Here we studied the kinetics and magnitude of induction of type I and type III IFN transcripts by primary porcine airway epithelial cells (pAECs) in response to swine and human origin IAV. We observed that swine influenza viruses (SIV) replicate more efficiently than the human pandemic influenza A/California/2009 (pH1N1 CA/09) in pAECs. Interestingly, we also found significant difference in kinetics of IFN-β, IFN-λ1 and IFN-λ3 gene expression by these viruses. While there was delay of up to 12 hours post infection (h p.i.) in induction of IFN genes in pAECs infected with swine IAV A/Sw/Illinois/2008 (H1N1 IL/08), human pH1N1 CA/09 rapidly induced IFN-β, IFN-λ1 and IFN-λ3 gene expression as early as 4 h p.i. However, the magnitude of IFN-β and IFN-λ3 induction at 24 h p.i. was not significantly different between the viral strains tested. Additionally, we found that swine H1N1 IL/08 was less sensitive to dsRNA induced antiviral response compared to human pH1N1 CA/09. Our data suggest that the human and swine IAVs differ in their ability to induce and respond to type I and type III interferons in swine cells. Swine origin IAV may have adapted to the pig host by subverting innate antiviral responses to viral infection. PMID:26384331

  8. Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants.

    PubMed

    Fu, Wenqing; O'Connor, Timothy D; Jun, Goo; Kang, Hyun Min; Abecasis, Goncalo; Leal, Suzanne M; Gabriel, Stacey; Rieder, Mark J; Altshuler, David; Shendure, Jay; Nickerson, Deborah A; Bamshad, Michael J; Akey, Joshua M

    2013-01-10

    Establishing the age of each mutation segregating in contemporary human populations is important to fully understand our evolutionary history and will help to facilitate the development of new approaches for disease-gene discovery. Large-scale surveys of human genetic variation have reported signatures of recent explosive population growth, notable for an excess of rare genetic variants, suggesting that many mutations arose recently. To more quantitatively assess the distribution of mutation ages, we resequenced 15,336 genes in 6,515 individuals of European American and African American ancestry and inferred the age of 1,146,401 autosomal single nucleotide variants (SNVs). We estimate that approximately 73% of all protein-coding SNVs and approximately 86% of SNVs predicted to be deleterious arose in the past 5,000-10,000 years. The average age of deleterious SNVs varied significantly across molecular pathways, and disease genes contained a significantly higher proportion of recently arisen deleterious SNVs than other genes. Furthermore, European Americans had an excess of deleterious variants in essential and Mendelian disease genes compared to African Americans, consistent with weaker purifying selection due to the Out-of-Africa dispersal. Our results better delimit the historical details of human protein-coding variation, show the profound effect of recent human history on the burden of deleterious SNVs segregating in contemporary populations, and provide important practical information that can be used to prioritize variants in disease-gene discovery. PMID:23201682

  9. Suitability of human and mammalian cells of different origin for the assessment of genotoxicity of metal and polymeric engineered nanoparticles.

    PubMed

    Cowie, Hilary; Magdolenova, Zuzana; Saunders, Margaret; Drlickova, Martina; Correia Carreira, Sara; Halamoda Kenzaoi, Blanka; Gombau, Lourdes; Guadagnini, Rina; Lorenzo, Yolanda; Walker, Laura; Fjellsbø, Lise Marie; Huk, Anna; Rinna, Alessandra; Tran, Lang; Volkovova, Katarina; Boland, Sonja; Juillerat-Jeanneret, Lucienne; Marano, Francelyne; Collins, Andrew R; Dusinska, Maria

    2015-05-01

    Nanogenotoxicity is a crucial endpoint in safety testing of nanomaterials as it addresses potential mutagenicity, which has implications for risks of both genetic disease and carcinogenesis. Within the NanoTEST project, we investigated the genotoxic potential of well-characterised nanoparticles (NPs): titanium dioxide (TiO2) NPs of nominal size 20 nm, iron oxide (8 nm) both uncoated (U-Fe3O4) and oleic acid coated (OC-Fe3O4), rhodamine-labelled amorphous silica 25 (Fl-25 SiO2) and 50 nm (Fl-50 SiO) and polylactic glycolic acid polyethylene oxide polymeric NPs - as well as Endorem® as a negative control for detection of strand breaks and oxidised DNA lesions with the alkaline comet assay. Using primary cells and cell lines derived from blood (human lymphocytes and lymphoblastoid TK6 cells), vascular/central nervous system (human endothelial human cerebral endothelial cells), liver (rat hepatocytes and Kupffer cells), kidney (monkey Cos-1 and human HEK293 cells), lung (human bronchial 16HBE14o cells) and placenta (human BeWo b30), we were interested in which in vitro cell model is sufficient to detect positive (genotoxic) and negative (non-genotoxic) responses. All in vitro studies were harmonized, i.e. NPs from the same batch, and identical dispersion protocols (for TiO2 NPs, two dispersions were used), exposure time, concentration range, culture conditions and time-courses were used. The results from the statistical evaluation show that OC-Fe3O4 and TiO2 NPs are genotoxic in the experimental conditions used. When all NPs were included in the analysis, no differences were seen among cell lines - demonstrating the usefulness of the assay in all cells to identify genotoxic and non-genotoxic NPs. The TK6 cells, human lymphocytes, BeWo b30 and kidney cells seem to be the most reliable for detecting a dose-response. PMID:25923348

  10. Genetics and biology of human ovarian teratomas. III. Cytogenetics and origins of malignant ovarian germ cell tumors.

    PubMed

    Hoffner, L; Shen-Schwarz, S; Deka, R; Chakravarti, A; Surti, U

    1992-08-01

    This report presents cytogenetic data on three cases of malignant ovarian germ cell tumors. All were diagnosed as malignant teratoma; case 1 with yolk sac elements; case 2 with elements of endodermal sinus tumor, embryonal carcinoma, and choriocarcinoma; and case 3 with yolk sac elements and embryonal carcinoma. Metaphase cells from each tumor, and normal tissue from the host, were karyotyped and scored for centromeric heteromorphisms in an attempt to determine the mechanism of origin. The karyotypes were 79,XXX,+1,+3,-6,+8,+12,+14,-15,+17, +20,+21,+22;49,XX,+8,+12,+22; and 48,XX,+3,+14, respectively. The analysis of centromeric heteromorphisms and DNA fingerprints of host and teratoma using the M13 probe revealed that one case originated from a germ cell before the first meiotic division. Normal host tissue was not available in case 2, but several centromeric markers were heterozygous in the tumor, indicating either meiosis I error or complete failure of germ cell meiosis. In the third case the centromeric heteromorphisms that were heterozygous in the host appeared to be homozygous for certain chromosomes and heterozygous for others in the tumor. These results suggest that germ cell teratomas could arise by the fusion of two ova. PMID:1521236

  11. Molecular identification by RNA-RNA hybridization of a human rotavirus that is closely related to rotaviruses of feline and canine origin.

    PubMed Central

    Nakagomi, O; Ohshima, A; Aboudy, Y; Shif, I; Mochizuki, M; Nakagomi, T; Gotlieb-Stematsky, T

    1990-01-01

    With a few exceptions subgroup I group A human rotavirus strains have short RNA patterns, whereas most animal rotavirus strains belong to subgroup I and have long RNA patterns. Thus, new isolates of subgroup I human rotaviruses with long RNA patterns are considered to have a high likelihood of being animal rotaviruses. A group of human rotaviruses represented by the AU-1 strain has recently been shown to be genetically related to a feline rotavirus (FRV-1) isolated in Japan. A human rotavirus, strain Ro1845, which is similar to the AU-1 strain in its subgroup (I), serotype (3), and electropherotype (long), was compared with various human and animal strains by RNA-RNA hybridization to determine its genogroup, a term proposed to classify rotaviruses based on their gene homology. The Ro1845 strain did not show a significant level of homology with AU-1, FRV-1, or other human strains, indicating that the Ro1845 strain is different in its genogroup not only from the AU-1 strain but also from other human strains. However, the Ro1845 strain showed a high degree of homology with another feline rotavirus (Cat97) isolated previously in Australia, suggesting that the Ro1845 strain might originate from a feline rotavirus that is genetically distinct from the Japanese FRV-1 strain. Furthermore, the Ro1845 strain as well as the Cat97 strain were related genetically to the canine rotavirus RS15 strain. Taken together, these results indicate that at least two genogroups are present in feline rotaviruses, one resembling the AU-1 strain and the other resembling the Ro1845 strain as well as canine rotaviruses. Images PMID:2166076

  12. Practical identification of human originated Lactobacillus species by amplified ribosomal DNA restriction analysis (ARDRA) for probiotic use.

    PubMed

    Öztürk, Mehmet; Meterelliyöz, Merve

    2015-08-01

    Probiotics are gaining popularity and increasing the importance of their accurate speciation. Lactobacillus species are commonly used as probiotic strains mostly of clinical importance. Present knowledge indicates that at least 14 Lactobacillus species are associated with the human intestinal tract. Currently, researchers are interested in developing efficient techniques for screening and selecting probiotics bacteria, but unfortunately most of these methods are time-consuming, labor-intensive and costly. The aim of this study is to develop reliable, rapid and accurate method to identify 14 references Lactobacillus species that could have been found in the human alimentary tract by 16S ribosomal DNA restriction analysis. In this study, to develop an effective method for the genotype-based identification of the reference Lactobacillus species, 1.5 kb of 16S rRNA nucleotide sequences of 14 Lactobacillus were collected from the Gene Bank aligned, in silico restricted and analyzed in respect to their 16S-rRNA restriction fragment polymorphism. In silico restriction profiles of 16S-rRNA indicated that FspBI, HinfI and DraI restriction enzymes (RE) are convenient for differentiation of 14 Lactobacillus species in human intestinal tract except Lb. casei and Lb. paracasei. The patterns of our experimental findings obtained from 16S PCR-ARDRA completely confirmed our in silico patterns. The present work demonstrated that 16S PCR-ARDRA method with FspBI, HinfI and DraI RE is a rapid, accurate and reliable method for the identification of Lactobacillus species from human alimentary tract, especially during the identification of large numbers of isolates and any laboratory equipped with a thermo cycler for probiotic use. PMID:25860079

  13. Widespread detection of human- and ruminant-origin Bacteroidales markers in subtidal waters of the Salish Sea in Washington State.

    PubMed

    Oyafuso, Zack S; Baxter, Anne E; Hall, Jason E; Naman, Sean M; Greene, Correigh M; Rhodes, Linda D

    2015-09-01

    Rising populations around coastal systems are increasing the threats to marine water quality. To assess anthropogenic fecal influence, subtidal waters were examined monthly for human- and ruminant-sourced Bacteroidales markers at 80 sites across six oceanographic basins of the Salish Sea (Washington State) from April through October, 2011. In the basins containing cities with individual populations>190,000, >50% of sites were positive for the human marker, while in the basins with high densities of dairy and cattle operations, ∼30% of sites were positive for the ruminant marker. Marker prevalence was elevated in spring (April and May) and fall (October) and reduced during summer (June through September), corresponding with seasonal precipitation. By logistic regression, the odds of human marker detection increased with percentage of adjacent catchment impervious surface, dissolved nitrate concentration, and abundance of low nucleic acid bacteria, but decreased with salinity and chlorophyll fluorescence. The odds of ruminant marker detection increased with dissolved ammonium concentration, mean flow rate for the nearest river, and adjacent shoreline length. These relationships are consistent with terrestrial to marine water flow as a transport mechanism. Thus, Bacteroidales markers traditionally used for identifying nearby sources can be used for assessing anthropogenic fecal inputs to regional marine ecosystems. PMID:26322768

  14. Sensitivity to the visual field origin of natural image patches in human low-level visual cortex

    PubMed Central

    2015-01-01

    Asymmetries in the response to visual patterns in the upper and lower visual fields (above and below the centre of gaze) have been associated with ecological factors relating to the structure of typical visual environments. Here, we investigated whether the content of the upper and lower visual field representations in low-level regions of human visual cortex are specialised for visual patterns that arise from the upper and lower visual fields in natural images. We presented image patches, drawn from above or below the centre of gaze of an observer navigating a natural environment, to either the upper or lower visual fields of human participants (n = 7) while we used functional magnetic resonance imaging (fMRI) to measure the magnitude of evoked activity in the visual areas V1, V2, and V3. We found a significant interaction between the presentation location (upper or lower visual field) and the image patch source location (above or below fixation); the responses to lower visual field presentation were significantly greater for image patches sourced from below than above fixation, while the responses in the upper visual field were not significantly different for image patches sourced from above and below fixation. This finding demonstrates an association between the representation of the lower visual field in human visual cortex and the structure of the visual input that is likely to be encountered below the centre of gaze. PMID:26131378

  15. Expression of the human amylase genes: Recent origin of a salivary amylase promoter from an actin pseudogene

    SciTech Connect

    Samuelson, L.C.; Gumucio, D.L.; Meisler, M.H. ); Wiebauer, K. )

    1988-09-12

    The human genes encoding salivary amylase (AMY1) and pancreatic amylase (AMY2) are nearly identical in structure and sequence. The authors have used ribonuclease protection studies to identify the functional gene copies in this multigene family. Riboprobes derived from each gene were hybridized to RNA from human pancreas, parotid and liver. The sizes of the protected fragments demonstrated that both pancreatic genes are expressed in pancreas. One of the pancreatic genes, AMY2B, is also transcribed at a low level in liver, but not from the promoter used in pancreas. AMY1 transcripts were detected in parotid, but not in pancreas or liver. Unexpected fragments protected by liver RNA led to the discovery that the 5{prime} regions of the five human amylase genes contain a processed {gamma}-actin pseudogene. The promoter and start site for transcription of AMY1 are recently derived from the 3{prime} untranslated region of {gamma}-actin. In addition, insertion of an endogenous retrovirus has interrupted the {gamma}-actin pseudogene in four of the five amylase genes.

  16. Risk potentials for humans of original and remediated PAH-contaminated soils: application of biomarkers of effect.

    PubMed

    Roos, Peter H; Tschirbs, Sebastian; Pfeifer, Frank; Welge, Peter; Hack, Alfons; Wilhelm, Michael; Bolt, Hermann M

    2004-12-15

    Contaminated soils represent a potential health risk for the human population. Risk assessment for humans requires specific methods, which must reflect the peculiarities of human behaviour, physiology and biochemistry with respect to contaminant uptake and processing. Biomarkers of effect or exposure have become an appropriate tool. Organic pollutants influence the expression profile of cytochromes P450 (CYP), and CYP1A1 has been shown to be a suitable biomarker for polycyclic aromatic hydrocarbons (PAH). The latter are widely distributed in soils and constitute an important soil contamination. Upon intake of PAH-contaminated soils, CYP1A1 is induced in various organs of rats and minipigs. Increased CYP1A1-levels in lung, kidney and spleen, after oral soil intake, indicate that contaminants escape the primary duodenal and hepatic metabolism and reach further organs. Dose-response relationships reveal that induction effects are to be expected in children based on known exposure conditions. Generally, CYP1A1-induction does not correlate with results of toxicity tests with lower organisms, performed with the same soils. The organic carbon content is largely responsible for this discrepancy. It severely affects the toxicity of soil bound PAH for microorganisms, but obviously affects the mobilization efficiency for PAH in the gastro-intestinal tract of mammals to a minor extent. Soil remediation by different methods may result in a significant reduction of the PAH content and of toxicity. Ingestion of remediated soils by rats shows, however, that the induction potential for CYP1A1 is only slightly decreased after remediation. This means that the major inducing components resist biological remediation or soil washing and remain in the soil. Because data obtained with experimental animals form the guiding principle for in vitro tests to be developed, the suitability of the animal model used for extrapolations to humans has to be proven. Upon soil ingestion, minipigs show a tissue-specific response pattern, which substantially differs from that of rats, which are widely used as animal models. It is not known which response pattern resembles that of man. In summary, cytochromes P450, in particular CYP1A1, are suitable biomarkers to assess the bioavailability of soil bound contaminants and their effects on mammalian species. There are, however, a number of questions to be answered in order to develop an in vitro test for human risk assessment. This concerns, for example, the identification of the suitable animal model, the identification of biomarkers for other contaminants and concepts to transpose the in vivo data to in vitro technologies or to mathematical modelling. PMID:15464628

  17. Evidence that the negative BOLD response is neuronal in origin: a simultaneous EEG-BOLD-CBF study in humans.

    PubMed

    Mullinger, K J; Mayhew, S D; Bagshaw, A P; Bowtell, R; Francis, S T

    2014-07-01

    Unambiguous interpretation of changes in the BOLD signal is challenging because of the complex neurovascular coupling that translates changes in neuronal activity into the subsequent haemodynamic response. In particular, the neurophysiological origin of the negative BOLD response (NBR) remains incompletely understood. Here, we simultaneously recorded BOLD, EEG and cerebral blood flow (CBF) responses to 10 s blocks of unilateral median nerve stimulation (MNS) in order to interrogate the NBR. Both negative BOLD and negative CBF responses to MNS were observed in the same region of the ipsilateral primary sensorimotor cortex (S1/M1) and calculations showed that MNS induced a decrease in the cerebral metabolic rate of oxygen consumption (CMRO2) in this NBR region. The ∆CMRO2/∆CBF coupling ratio (n) was found to be significantly larger in this ipsilateral S1/M1 region (n=0.91±0.04, M=10.45%) than in the contralateral S1/M1 (n=0.65±0.03, M=10.45%) region that exhibited a positive BOLD response (PBR) and positive CBF response, and a consequent increase in CMRO2 during MNS. The fMRI response amplitude in ipsilateral S1/M1 was negatively correlated with both the power of the 8-13 Hz EEG mu oscillation and somatosensory evoked potential amplitude. Blocks in which the largest magnitude of negative BOLD and CBF responses occurred therefore showed greatest mu power, an electrophysiological index of cortical inhibition, and largest somatosensory evoked potentials. Taken together, our results suggest that a neuronal mechanism underlies the NBR, but that the NBR may originate from a different neurovascular coupling mechanism to the PBR, suggesting that caution should be taken in assuming the NBR simply represents the neurophysiological inverse of the PBR. PMID:24632092

  18. Characteristics of Mesenchymal Stem Cells Originating from the Bilateral Inferior Turbinate in Humans with Nasal Septal Deviation

    PubMed Central

    Choi, Jin; Lee, Dong Chang; Oh, Jeong Hoon; Kim, Sung Won; Kim, Jin Bae

    2014-01-01

    Background and objectives Nasal septal deviation (NSD) is often associated with overgrowth of the unilateral inferior turbinate. In vivo and in vitro studies indicate that human mesenchymal stem cells (MSCs) are able to differentiate into multiple cell types, including osteoblasts. We tested the hypothesis that turbinate size affects human turbinate-derived MSC (hTMSCs) quantity, proliferation, and differentiation into osteogenic lineages, and that hypertrophic turbinates may predispose to NSD on the contralateral side. Subjects and Methods The hypertrophic and contralateral inferior turbinate tissues used in our study were obtained and cultured from the tissue discarded from 10 patients who underwent septoplasty and partial turbinectomy. After isolating the hTMSCs from both turbinates, the cells were enumerated using an automated cell counter. The expression of surface markers for MSCs over four passages was assessed by fluorescent-activated cell sorting analysis (FACS), and cell proliferation was assessed using a cell counting kit (CCK)-8 according to turbinate size. In addition, osteogenic differentiation of hTMSCs was identified using alkaline phosphatase (ALP) and alizarin red S staining, after which osteoblastic gene expression was evaluated. Results There was no significant difference in the number of hTMSCs. FACS analysis revealed that the hTMSCs were negative for CD14, CD19, CD34, and HLA-DR, and positive for CD29, CD73, and CD90, representing a characteristic MSC phenotype, with no significant difference between the two groups. The cellular proliferation and osteogenic differentiation potential of the hTMSCs were also not significantly different between the two groups. Conclusions We conclude that turbinate size does not affect the characterization, proliferation, and osteogenic differentiation potential of hTMSCs in vitro test, and therefore should not affect the clinical decision of whether to use autologous or allogenic hTMSCs. However, more experiments are required to definitively state the relationship of hTMSCs with turbinate size or the process NSD in humans. PMID:24926874

  19. Apolipoprotein E Variation at the Sequence Haplotype Level: Implications for the Origin and Maintenance of a Major Human Polymorphism

    PubMed Central

    Fullerton, Stephanie M.; Clark, Andrew G.; Weiss, Kenneth M.; Nickerson, Deborah A.; Taylor, Scott L.; Stengrd, Jari H.; Salomaa, Veikko; Vartiainen, Erkki; Perola, Markus; Boerwinkle, Eric; Sing, Charles F.

    2000-01-01

    Three common protein isoforms of apolipoprotein E (apoE), encoded by the ?2, ?3, and ?4 alleles of the APOE gene, differ in their association with cardiovascular and Alzheimer's disease risk. To gain a better understanding of the genetic variation underlying this important polymorphism, we identified sequence haplotype variation in 5.5 kb of genomic DNA encompassing the whole of the APOE locus and adjoining flanking regions in 96 individuals from four populations: blacks from Jackson, MS (n=48 chromosomes), Mayans from Campeche, Mexico (n=48), Finns from North Karelia, Finland (n=48), and non-Hispanic whites from Rochester, MN (n=48). In the region sequenced, 23 sites varied (21 single nucleotide polymorphisms, or SNPs, 1 diallelic indel, and 1 multiallelic indel). The 22 diallelic sites defined 31 distinct haplotypes in the sample. The estimate of nucleotide diversity (site-specific heterozygosity) for the locus was 0.00050.0003. Sequence analysis of the chimpanzee APOE gene showed that it was most closely related to human ?4-type haplotypes, differing from the human consensus sequence at 67 synonymous (54 substitutions and 13 indels) and 9 nonsynonymous fixed positions. The evolutionary history of allelic divergence within humans was inferred from the pattern of haplotype relationships. This analysis suggests that haplotypes defining the ?3 and ?2 alleles are derived from the ancestral ?4s and that the ?3 group of haplotypes have increased in frequency, relative to ?4s, in the past 200,000 years. Substantial heterogeneity exists within all three classes of sequence haplotypes, and there are important interpopulation differences in the sequence variation underlying the protein isoforms that may be relevant to interpreting conflicting reports of phenotypic associations with variation in the common protein isoforms. PMID:10986041

  20. Origins of the High Catalytic Activity of Human Alcohol Dehydrogenase 4 Studied with Horse Liver A317C Alcohol Dehydrogenase

    PubMed Central

    Herdendorf, Timothy J.; Plapp, Bryce V.

    2011-01-01

    The turnover numbers and other kinetic constants for human alcohol dehydrogenase (ADH) 4 (“stomach” isoenzyme) are substantially larger (10–100-fold) than those for human class I and horse liver alcohol dehydrogenases. Comparison of the primary amino acid sequences (69% identity) and tertiary structures of these enzymes led to the suggestion that residue 317, which makes a hydrogen bond with the nicotinamide amide nitrogen of the coenzyme, may account for these differences. Ala-317 in the class I enzymes is substituted with Cys in human ADH4, and locally different conformations of the peptide backbones could affect coenzyme binding. This hypothesis was tested by making the A317C substitution in horse liver ADH1E and comparisons to the wild-type ADH1E. The steady-state kinetic constants for the oxidation of benzyl alcohol and the reduction of benzaldehyde catalyzed by the A317C enzyme were very similar (up to about 2-fold differences) to those for the wild-type enzyme. Transient kinetics showed that the rate constants for binding of NAD+ and NADH were also similar. Transient reaction data were fitted to the full ordered bi bi mechanism and showed that the rate constants for hydride transfer decreased by about 2.8-fold with the A317C substitution. The structure of A317C ADH1E complexed with NAD+ and 2,3,4,5,6-pentafluorobenzyl alcohol at 1.2 Ǻ resolution is essentially identical to the structure of the wild-type enzyme, except near residue 317 where the additional sulfhydryl group displaces a water molecule that is present in the wild-type enzyme. ADH is adaptable and can tolerate internal substitutions, but the protein dynamics apparently are affected, as reflected in rates of hydride transfer. The A317C substitution is not solely responsible for the larger kinetic constants in human ADH4; thus, the differences in catalytic activity must arise from one or more of the other hundred substitutions in the enzyme. PMID:21184752

  1. A glimpse into the early origins of medieval anatomy through the oldest conserved human dissection (Western Europe, 13th c. A.D.)

    PubMed Central

    Huynh-Charlier, Isabelle; Poupon, Joël; Lancelot, Eloïse; Campos, Paula F.; Favier, Dominique; Jeannel, Gaël-François; Bonati, Maurizio Rippa; de la Grandmaison, Geoffroy Lorin; Hervé, Christian

    2013-01-01

    Introduction Medieval autopsy practice is very poorly known in Western Europe, due to a lack of both descriptive medico-surgical texts and conserved dissected human remains. This period is currently considered the dark ages according to a common belief of systematic opposition of Christian religious authorities to the opening of human cadavers. Material and methods The identification in a private collection of an autopsied human individual dated from the 13th century A.D. is an opportunity for better knowledge of such practice in this chrono-cultural context, i.e. the early origins of occidental dissections. A complete forensic anthropological procedure was carried out, completed by radiological and elemental analyses. Results The complete procedure of this body opening and internal organs exploration is explained, and compared with historical data about forensic and anatomical autopsies from this period. During the analysis, a red substance filling all arterial cavities, made of mercury sulfide (cinnabar) mixed with vegetal oil (oleic and palmitic acids) was identified; it was presumably used to highlight vascularization by coloring in red such vessels, and help in the preservation of the body. Conclusions Of particular interest for the description of early medical and anatomical knowledge, this “human preparation” is the oldest known yet, and is particularly important for the fields of history of medicine, surgery and anatomical practice. PMID:24904674

  2. Human de novo papillary renal-cell carcinomas in a kidney graft: evidence of recipient origin with adenoma-carcinoma sequence.

    PubMed

    Verine, J; Varna, M; Ratajczak, P; El-Bouchtaoui, M; Leboeuf, C; Plassa, L-F; Soliman, H; Sandid, W; Abboud, I; Bousquet, G; Verneuil, L; Peraldi, M-N; Mongiat-Artus, P; Janin, A

    2013-04-01

    Papillary renal-cell carcinoma (pRCC) is unusual for its occurrence in kidneys with chronic dysfunction, for its frequent multifocality and for its common association with papillary adenoma, a benign renal lesion morphologically indistinguishable from pRCC. Concomitant development of papillary adenoma and pRCC in five transplanted kidneys, where donor and recipient characteristics are well established, provided a unique opportunity for molecular studies of de novo pRCC carcinogenesis. We aimed to study this tumor type to determine whether or not the different papillary tumors have the same origin, and whether or not papillary adenomas are precursor lesions of pRCC. We performed XY-FISH in sex-mismatched kidney transplants, and polymorphic microsatellite DNA and high-resolution melting of mitochondrial DNA analyzes in all five patients on laser-microdissected tumor cells, then compared these molecular profiles to donor and recipient profiles. This study (i) identified the recipient origin of de novo papillary adenomas and pRCCs in a kidney transplant, (ii) demonstrated an identical origin for precursor cells of papillary adenomas and pRCCs and (iii) showed additional genetic alterations in pRCCs compared to papillary adenomas. This molecular approach of papillary tumors developed in transplanted kidney identified successive steps in carcinogenesis of human de novo papillary renal-cell carcinoma. PMID:23425311

  3. Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of human imprinting and suggests a germline methylation-independent mechanism of establishment

    PubMed Central

    Court, Franck; Tayama, Chiharu; Romanelli, Valeria; Martin-Trujillo, Alex; Iglesias-Platas, Isabel; Okamura, Kohji; Sugahara, Naoko; Simón, Carlos; Moore, Harry; Harness, Julie V.; Keirstead, Hans; Sanchez-Mut, Jose Vicente; Kaneki, Eisuke; Lapunzina, Pablo; Soejima, Hidenobu; Wake, Norio; Esteller, Manel; Ogata, Tsutomu; Hata, Kenichiro; Nakabayashi, Kazuhiko; Monk, David

    2014-01-01

    Differential methylation between the two alleles of a gene has been observed in imprinted regions, where the methylation of one allele occurs on a parent-of-origin basis, the inactive X-chromosome in females, and at those loci whose methylation is driven by genetic variants. We have extensively characterized imprinted methylation in a substantial range of normal human tissues, reciprocal genome-wide uniparental disomies, and hydatidiform moles, using a combination of whole-genome bisulfite sequencing and high-density methylation microarrays. This approach allowed us to define methylation profiles at known imprinted domains at base-pair resolution, as well as to identify 21 novel loci harboring parent-of-origin methylation, 15 of which are restricted to the placenta. We observe that the extent of imprinted differentially methylated regions (DMRs) is extremely similar between tissues, with the exception of the placenta. This extra-embryonic tissue often adopts a different methylation profile compared to somatic tissues. Further, we profiled all imprinted DMRs in sperm and embryonic stem cells derived from parthenogenetically activated oocytes, individual blastomeres, and blastocysts, in order to identify primary DMRs and reveal the extent of reprogramming during preimplantation development. Intriguingly, we find that in contrast to ubiquitous imprints, the majority of placenta-specific imprinted DMRs are unmethylated in sperm and all human embryonic stem cells. Therefore, placental-specific imprinting provides evidence for an inheritable epigenetic state that is independent of DNA methylation and the existence of a novel imprinting mechanism at these loci. PMID:24402520

  4. Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk

    PubMed Central

    Alsaweed, Mohammed; Lai, Ching Tat; Hartmann, Peter E.; Geddes, Donna T.; Kakulas, Foteini

    2016-01-01

    Human milk (HM) contains regulatory biomolecules including miRNAs, the origin and functional significance of which are still undetermined. We used TaqMan OpenArrays to profile 681 mature miRNAs in HM cells and fat, and compared them with maternal peripheral blood mononuclear cells (PBMCs) and plasma, and bovine and soy infant formulae. HM cells and PBMCs (292 and 345 miRNAs, respectively) had higher miRNA content than HM fat and plasma (242 and 219 miRNAs, respectively) (p < 0.05). A strong association in miRNA profiles was found between HM cells and fat, whilst PBMCs and plasma were distinctly different to HM, displaying marked inter-individual variation. Considering the dominance of epithelial cells in mature milk of healthy women, these results suggest that HM miRNAs primarily originate from the mammary epithelium, whilst the maternal circulation may have a smaller contribution. Our findings demonstrate that unlike infant formulae, which contained very few human miRNA, HM is a rich source of lactation-specific miRNA, which could be used as biomarkers of the performance and health status of the lactating mammary gland. Given the recently identified stability, uptake and functionality of food- and milk-derived miRNA in vivo, HM miRNA are likely to contribute to infant protection and development. PMID:26854194

  5. Distribution of Class 1 Integrons with IS26-Mediated Deletions in Their 3′-Conserved Segments in Escherichia coli of Human and Animal Origin

    PubMed Central

    Dawes, Fay E.; Kuzevski, Alexander; Bettelheim, Karl A.; Hornitzky, Michael A.; Djordjevic, Steven P.; Walker, Mark J.

    2010-01-01

    Class 1 integrons play a role in the emergence of multi-resistant bacteria by facilitating the recruitment of gene cassettes encoding antibiotic resistance genes. 512 E. coli strains sourced from humans (n = 202), animals (n = 304) and the environment (n = 6) were screened for the presence of the intI1 gene. In 31/79 integron positive E. coli strains, the gene cassette regions could not be PCR amplified using standard primers. DNA sequence analysis of 6 serologically diverse strains revealed atypical integrons harboured the dfrA5 cassette gene and only 24 bp of the integron 3′-conserved segment (CS) remained, due to the insertion of IS26. PCR targeting intI1 and IS26 followed by restriction fragment length polymorphism (RFLP) analysis identified the integron-dfrA5-IS26 element in 27 E. coli strains of bovine origin and 4 strains of human origin. Southern hybridization and transformation studies revealed the integron-dfrA5-IS26 gene arrangement was either chromosomally located or plasmid borne. Plasmid location in 4/9 E. coli strains and PCR linkage of Tn21 transposition genes with the intI1 gene in 20/31 strains, suggests this element is readily disseminated by horizontal transfer. PMID:20856797

  6. Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk.

    PubMed

    Alsaweed, Mohammed; Lai, Ching Tat; Hartmann, Peter E; Geddes, Donna T; Kakulas, Foteini

    2016-01-01

    Human milk (HM) contains regulatory biomolecules including miRNAs, the origin and functional significance of which are still undetermined. We used TaqMan OpenArrays to profile 681 mature miRNAs in HM cells and fat, and compared them with maternal peripheral blood mononuclear cells (PBMCs) and plasma, and bovine and soy infant formulae. HM cells and PBMCs (292 and 345 miRNAs, respectively) had higher miRNA content than HM fat and plasma (242 and 219 miRNAs, respectively) (p?originate from the mammary epithelium, whilst the maternal circulation may have a smaller contribution. Our findings demonstrate that unlike infant formulae, which contained very few human miRNA, HM is a rich source of lactation-specific miRNA, which could be used as biomarkers of the performance and health status of the lactating mammary gland. Given the recently identified stability, uptake and functionality of food- and milk-derived miRNA in vivo, HM miRNA are likely to contribute to infant protection and development. PMID:26854194

  7. Do human extraintestinal Escherichia coli infections resistant to expanded-spectrum cephalosporins originate from food-producing animals? A systematic review.

    PubMed

    Lazarus, Benjamin; Paterson, David L; Mollinger, Joanne L; Rogers, Benjamin A

    2015-02-01

    To find out whether food-producing animals (FPAs) are a source of extraintestinal expanded-spectrum cephalosporin-resistant Escherichia coli (ESCR-EC) infections in humans, Medline, Embase, and the Cochrane Database of Systematic Reviews were systematically reviewed. Thirty-four original, peer-reviewed publications were identified for inclusion. Six molecular epidemiology studies supported the transfer of resistance via whole bacterium transmission (WBT), which was best characterized among poultry in the Netherlands. Thirteen molecular epidemiology studies supported transmission of resistance via mobile genetic elements, which demonstrated greater diversity of geography and host FPA. Seventeen molecular epidemiology studies did not support WBT and two did not support mobile genetic element-mediated transmission. Four observational epidemiology studies were consistent with zoonotic transmission. Overall, there is evidence that a proportion of human extraintestinal ESCR-EC infections originate from FPAs. Poultry, in particular, is probably a source, but the quantitative and geographical extent of the problem is unclear and requires further investigation. PMID:25301206

  8. Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of human imprinting and suggests a germline methylation-independent mechanism of establishment.

    PubMed

    Court, Franck; Tayama, Chiharu; Romanelli, Valeria; Martin-Trujillo, Alex; Iglesias-Platas, Isabel; Okamura, Kohji; Sugahara, Naoko; Simón, Carlos; Moore, Harry; Harness, Julie V; Keirstead, Hans; Sanchez-Mut, Jose Vicente; Kaneki, Eisuke; Lapunzina, Pablo; Soejima, Hidenobu; Wake, Norio; Esteller, Manel; Ogata, Tsutomu; Hata, Kenichiro; Nakabayashi, Kazuhiko; Monk, David

    2014-04-01

    Differential methylation between the two alleles of a gene has been observed in imprinted regions, where the methylation of one allele occurs on a parent-of-origin basis, the inactive X-chromosome in females, and at those loci whose methylation is driven by genetic variants. We have extensively characterized imprinted methylation in a substantial range of normal human tissues, reciprocal genome-wide uniparental disomies, and hydatidiform moles, using a combination of whole-genome bisulfite sequencing and high-density methylation microarrays. This approach allowed us to define methylation profiles at known imprinted domains at base-pair resolution, as well as to identify 21 novel loci harboring parent-of-origin methylation, 15 of which are restricted to the placenta. We observe that the extent of imprinted differentially methylated regions (DMRs) is extremely similar between tissues, with the exception of the placenta. This extra-embryonic tissue often adopts a different methylation profile compared to somatic tissues. Further, we profiled all imprinted DMRs in sperm and embryonic stem cells derived from parthenogenetically activated oocytes, individual blastomeres, and blastocysts, in order to identify primary DMRs and reveal the extent of reprogramming during preimplantation development. Intriguingly, we find that in contrast to ubiquitous imprints, the majority of placenta-specific imprinted DMRs are unmethylated in sperm and all human embryonic stem cells. Therefore, placental-specific imprinting provides evidence for an inheritable epigenetic state that is independent of DNA methylation and the existence of a novel imprinting mechanism at these loci. PMID:24402520

  9. Effects of a Ceramic Biomaterial on Immune Modulatory Properties and Differentiation Potential of Human Mesenchymal Stromal Cells of Different Origin

    PubMed Central

    Bassi, Giulio; Guilloton, Fabien; Menard, Cedric; Di Trapani, Mariano; Deschaseaux, Frederic; Sensebé, Luc; Schrezenmeier, Hubert; Giordano, Rosaria; Bourin, Philippe; Dominici, Massimo

    2015-01-01

    The aim of this study was to assess the immune modulatory properties of human mesenchymal stromal cells obtained from bone marrow (BM-MSCs), fat (ASCs), and cord blood (CB-MSCs) in the presence of a hydroxyapatite and tricalcium-phosphate (HA/TCP) biomaterial as a scaffold for MSC delivery. In resting conditions, a short-term culture with HA/TCP did not modulate the anti-apoptotic and suppressive features of the various MSC types toward T, B, and NK cells; in addition, when primed with inflammatory cytokines, MSCs similarly increased their suppressive capacities in the presence or absence of HA/TCP. The long-term culture of BM-MSCs with HA/TCP induced an osteoblast-like phenotype with upregulation of OSTERIX and OSTEOCALCIN, similar to what was obtained with dexamethasone and, to a higher extent, with bone morphogenetic protein 4 (BMP-4) treatment. MSC-derived osteoblasts did not trigger immune cell activation, but were less efficient than undifferentiated MSCs in inhibiting stimulated T and NK cells. Interestingly, their suppressive machinery included not only the activation of indoleamine-2,3 dioxygenase (IDO), which plays a central role in T-cell inhibition, but also cyclooxygenase-2 (COX-2) that was not significantly involved in the immune modulatory effect of human undifferentiated MSCs. Since COX-2 is significantly involved in bone healing, its induction by HA/TCP could also contribute to the therapeutic activity of MSCs for bone tissue engineering. PMID:25322665

  10. Effects of a ceramic biomaterial on immune modulatory properties and differentiation potential of human mesenchymal stromal cells of different origin.

    PubMed

    Bassi, Giulio; Guilloton, Fabien; Menard, Cedric; Di Trapani, Mariano; Deschaseaux, Frederic; Sensebé, Luc; Schrezenmeier, Hubert; Giordano, Rosaria; Bourin, Philippe; Dominici, Massimo; Tarte, Karin; Krampera, Mauro

    2015-02-01

    The aim of this study was to assess the immune modulatory properties of human mesenchymal stromal cells obtained from bone marrow (BM-MSCs), fat (ASCs), and cord blood (CB-MSCs) in the presence of a hydroxyapatite and tricalcium-phosphate (HA/TCP) biomaterial as a scaffold for MSC delivery. In resting conditions, a short-term culture with HA/TCP did not modulate the anti-apoptotic and suppressive features of the various MSC types toward T, B, and NK cells; in addition, when primed with inflammatory cytokines, MSCs similarly increased their suppressive capacities in the presence or absence of HA/TCP. The long-term culture of BM-MSCs with HA/TCP induced an osteoblast-like phenotype with upregulation of OSTERIX and OSTEOCALCIN, similar to what was obtained with dexamethasone and, to a higher extent, with bone morphogenetic protein 4 (BMP-4) treatment. MSC-derived osteoblasts did not trigger immune cell activation, but were less efficient than undifferentiated MSCs in inhibiting stimulated T and NK cells. Interestingly, their suppressive machinery included not only the activation of indoleamine-2,3 dioxygenase (IDO), which plays a central role in T-cell inhibition, but also cyclooxygenase-2 (COX-2) that was not significantly involved in the immune modulatory effect of human undifferentiated MSCs. Since COX-2 is significantly involved in bone healing, its induction by HA/TCP could also contribute to the therapeutic activity of MSCs for bone tissue engineering. PMID:25322665

  11. Thermodynamic origins of protein folding, allostery, and capsid formation in the human hepatitis B virus core protein.

    PubMed

    Alexander, Crispin G; Jürgens, Maike C; Shepherd, Dale A; Freund, Stefan M V; Ashcroft, Alison E; Ferguson, Neil

    2013-07-23

    HBc, the capsid-forming "core protein" of human hepatitis B virus (HBV), is a multidomain, α-helical homodimer that aggressively forms human HBV capsids. Structural plasticity has been proposed to be important to the myriad functions HBc mediates during viral replication. Here, we report detailed thermodynamic analyses of the folding of the dimeric HBc protomer under conditions that prevented capsid formation. Central to our success was the use of ion mobility spectrometry-mass spectrometry and microscale thermophoresis, which allowed folding mechanisms to be characterized using just micrograms of protein. HBc folds in a three-state transition with a stable, dimeric, α-helical intermediate. Extensive protein engineering showed thermodynamic linkage between different structural domains. Unusual effects associated with mutating some residues suggest structural strain, arising from frustrated contacts, is present in the native dimer. We found evidence of structural gatekeepers that, when mutated, alleviated native strain and prevented (or significantly attenuated) capsid formation by tuning the population of alternative native conformations. This strain is likely an evolved feature that helps HBc access the different structures associated with its diverse essential functions. The subtle balance between native and strained contacts may provide the means to tune conformational properties of HBc by molecular interactions or mutations, thereby conferring allosteric regulation of structure and function. The ability to trap HBc conformers thermodynamically by mutation, and thereby ablate HBV capsid formation, provides proof of principle for designing antivirals that elicit similar effects. PMID:23824290

  12. Evaluation of the pathogenic potential, antimicrobial susceptibility, and genomic relations of Yersinia enterocolitica strains from food and human origin.

    PubMed

    Lucero-Estrada, Cecilia S M; Soria, José Miguel; Favier, Gabriela Isabel; Escudero, María Esther

    2015-11-01

    Yersinia enterocolitica is a food-borne pathogen that causes gastroenteritis with occasional postinfection sequels. This study was aimed to determinate the pathogenic potential, antimicrobial susceptibility, and genomic relationships of Y. enterocolitica strains of different bioserotypes (B/O) isolated from foods and human samples in San Luis, Argentina. Strains obtained by culture were bioserotyped and characterized by phenotypic and genotypic virulence markers, antimicrobial susceptibility, and pulsed-field gel electrophoresis (PFGE). Yersinia enterocolitica was detected in 9.2% of 380 samples, with a distribution of 10.6% (30/284) for food products and 5.2% (5/96) for human samples. Regarding the pathogenic potential, B1A strains of different serotypes were virF(-) ail(-), of which 72.0% (13/18) were ystB(+) with virulence-related phenotypic characteristics. Among B2/O:9 isolates, 75.0% (9/12) exhibited the genotype virF(+) ail(+) ystB(-) along with phenotypic traits associated with virulence; the same genotype was observed in 80.0% (4/5) of B3/O:3 and B3/O:5 strains. By PFGE, it was possible to separate Y. enterocolitica biotypes into 4 clonal groups (A to D) with 23 genomic types, generating a discriminatory index of 0.96. All isolates were susceptible to antimicrobials used for clinical treatment. This study highlights the presence of pathogenic bioserotypes and the high genomic diversity of the Y. enterocolitica strains isolated in our region. PMID:26370735

  13. Neanderthal origin of the haplotypes carrying the functional variant Val92Met in the MC1R in modern humans.

    PubMed

    Ding, Qiliang; Hu, Ya; Xu, Shuhua; Wang, Chuan-Chao; Li, Hui; Zhang, Ruyue; Yan, Shi; Wang, Jiucun; Jin, Li

    2014-08-01

    Skin color is one of the most visible and important phenotypes of modern humans. Melanocyte-stimulating hormone and its receptor played an important role in regulating skin color. In this article, we present evidence of Neanderthal introgression encompassing the melanocyte-stimulating hormone receptor gene MC1R. The haplotypes from Neanderthal introgression diverged with the Altai Neanderthal 103.3 ka, which postdates the anatomically modern human-Neanderthal divergence. We further discovered that all of the putative Neanderthal introgressive haplotypes carry the Val92Met variant, a loss-of-function variant in MC1R that is associated with multiple dermatological traits including skin color and photoaging. Frequency of this Neanderthal introgression is low in Europeans (∼5%), moderate in continental East Asians (∼30%), and high in Taiwanese aborigines (60-70%). As the putative Neanderthal introgressive haplotypes carry a loss-of-function variant that could alter the function of MC1R and is associated with multiple traits related to skin color, we speculate that the Neanderthal introgression may have played an important role in the local adaptation of Eurasians to sunlight intensity. PMID:24916031

  14. Analysis of oxygen metabolism implies a neural origin for the negative BOLD response in human visual cortex.

    PubMed

    Pasley, Brian N; Inglis, Ben A; Freeman, Ralph D

    2007-06-01

    The sustained negative blood oxygenation level-dependent (BOLD) response in functional MRI is observed universally, but its interpretation is controversial. The origin of the negative response is of fundamental importance because it could provide a measurement of neural deactivation. However, a substantial component of the negative response may be due to a non-neural hemodynamic artifact. To distinguish these possibilities, we have measured evoked BOLD, cerebral blood flow (CBF), and oxygen metabolism responses to a fixed visual stimulus from two different baseline conditions. One is a normal resting baseline, and the other is a lower baseline induced by a sustained negative response. For both baseline conditions, CBF and oxygen metabolism responses reach the same peak amplitude. Consequently, evoked responses from the negative baseline are larger than those from the resting baseline. The larger metabolic response from negative baseline presumably reflects a greater neural response that is required to reach the same peak amplitude as that from resting baseline. Furthermore, the ratio of CBF to oxygen metabolism remains approximately the same from both baseline states (approximately 2:1). This tight coupling between hemodynamic and metabolic components implies that the magnitude of any hemodynamic artifact is inconsequential. We conclude that the negative response is a functionally significant index of neural deactivation in early visual cortex. PMID:17113313

  15. Origin and Expansion of the Yunnan Shoot Borer, Tomicus yunnanensis (Coleoptera: Scolytinae): A Mixture of Historical Natural Expansion and Contemporary Human-Mediated Relocation

    PubMed Central

    Ma, Xue-yu; Chen, Jin-min; Li, Qing-qing; Ye, Hui

    2014-01-01

    The Yunnan shoot borer, Tomicus yunnanensis, is a recently-discovered, aggressive pest of the Yunnan pine stands in southwestern China. Despite many bionomics studies and massive controlling efforts, research on its population genetics is extremely limited. The present study, aimed at investigating the origin and dispersal of this important forestry pest, analyzed the population genetic structure and demographic history using a mitochondrial cox1 gene fragment. Our results showed that T. yunnanensis most likely originated from the Central-Yunnan Altiplano, and the divergence time analysis placed the origin approximately 0.72 million-years ago. Host separation and specialization might have caused the speciation of T. yunnanensis. Genetic structure analyses identified two population groups, with six populations near the origin area forming one group and the remaining six populations from western and eastern Yunnan and southwestern Sichuan comprising the other. Divergence time analysis placed the split of the two groups at approximately 0.60 million-years ago, and haplotype phylogenetic tree, network, as well as migration rate suggested that populations of the latter group were established via a small number of individuals from the former one. Migration analysis also showed a certain degree of recent expansion from southwestern Sichuan to eastern Yunnan. Our findings implied that T. yunnanensis underwent both historical expansion and recent dispersal. The historical expansion may relate to the oscillation of regional climate due to glacial and interglacial periods in the Pleistocene, while human-mediated transportation of pine-wood material might have assisted the relocation and establishment of this pest in novel habitats. PMID:25372458

  16. The Hominin Sites and Paleolakes Drilling Project (HSPDP): Understanding the paleoenvironmental and paleoclimatic context of human origins through continental drilling

    NASA Astrophysics Data System (ADS)

    Cohen, Andrew S.; Campisano, Christopher; Asrat, Asfawossen; Arrowsmith, Ramon; Deino, Alan; Feibel, Craig; Hill, Andrew; Kingston, John; Lamb, Henry; Lowenstein, Tim; Olago, Daniel; Bernhart Owen, R.; Renaut, Robin; Schabitz, Frank; Trauth, Martin

    2015-04-01

    The influence of climate and environmental history on human evolution is an existential question that continues to be hotly debated, in part because of the paucity of high resolution records collected in close proximity to the key fossil and archaeological evidence. To address this issue and transform the scientific debate, the HSPDP was developed to collect lacustrine sediment drill cores from basins in Kenya and Ethiopia that collectively encompass critical time intervals and locations for Plio-Quaternary human evolution in East Africa. After a 17 month campaign, drilling was completed in November, 2014, with over 1750m of core collected from 11 boreholes from five areas (1930m total drilling length, avg. 91% recovery). The sites, from oldest to youngest, include 1) N. Awash, Ethiopia (~3.5-2.9Ma core interval); 2) Baringo-Tugen Hills, Kenya (~3.3-2.5Ma); 3) West Turkana, Kenya (~1.9-1.4Ma); L. Magadi, Kenya (0.8-0Ma) and the Chew Bahir Basin, Ethiopia (~0.5-0Ma). Initial core description (ICD) and sampling for geochronology, geochemistry and paleoecology studies had been completed by mid2014, with the two remaining sites (Magadi and Chew Bahir) scheduled for ICD work in early 2015. Whereas the primary scientific targets were the lacustrine deposits from the hominin-bearing basin depocenters, many intervals of paleosols (representative of low lake stands and probable arid periods) were also encountered in drill cores. Preliminary analyses of drill core sedimentology and geochemistry show both long-term lake level changes and cyclic variability in lake levels, both of which may be indicative of climatic forcing events of interest to paleoanthropologists. Authors of this abstract also include the entire HSPDP field team.

  17. Strong Components of Epigenetic Memory in Cultured Human Fibroblasts Related to Site of Origin and Donor Age.

    PubMed

    Ivanov, Nikolay A; Tao, Ran; Chenoweth, Joshua G; Brandtjen, Anna; Mighdoll, Michelle I; Genova, John D; McKay, Ronald D; Jia, Yankai; Weinberger, Daniel R; Kleinman, Joel E; Hyde, Thomas M; Jaffe, Andrew E

    2016-02-01

    Differentiating pluripotent cells from fibroblast progenitors is a potentially transformative tool in personalized medicine. We previously identified relatively greater success culturing dura-derived fibroblasts than scalp-derived fibroblasts from postmortem tissue. We hypothesized that these differences in culture success were related to epigenetic differences between the cultured fibroblasts by sampling location, and therefore generated genome-wide DNA methylation and transcriptome data on 11 intrinsically matched pairs of dural and scalp fibroblasts from donors across the lifespan (infant to 85 years). While these cultured fibroblasts were several generations removed from the primary tissue and morphologically indistinguishable, we found widespread epigenetic differences by sampling location at the single CpG (N = 101,989), region (N = 697), "block" (N = 243), and global spatial scales suggesting a strong epigenetic memory of original fibroblast location. Furthermore, many of these epigenetic differences manifested in the transcriptome, particularly at the region-level. We further identified 7,265 CpGs and 11 regions showing significant epigenetic memory related to the age of the donor, as well as an overall increased epigenetic variability, preferentially in scalp-derived fibroblasts-83% of loci were more variable in scalp, hypothesized to result from cumulative exposure to environmental stimuli in the primary tissue. By integrating publicly available DNA methylation datasets on individual cell populations in blood and brain, we identified significantly increased inter-individual variability in our scalp- and other skin-derived fibroblasts on a similar scale as epigenetic differences between different lineages of blood cells. Lastly, these epigenetic differences did not appear to be driven by somatic mutation-while we identified 64 probable de-novo variants across the 11 subjects, there was no association between mutation burden and age of the donor (p = 0.71). These results depict a strong component of epigenetic memory in cell culture from primary tissue, even after several generations of daughter cells, related to cell state and donor age. PMID:26913521

  18. Strong Components of Epigenetic Memory in Cultured Human Fibroblasts Related to Site of Origin and Donor Age

    PubMed Central

    Ivanov, Nikolay A.; Tao, Ran; Chenoweth, Joshua G.; Brandtjen, Anna; Mighdoll, Michelle I.; Genova, John D.; McKay, Ronald D.; Jia, Yankai; Weinberger, Daniel R.; Kleinman, Joel E.; Hyde, Thomas M.; Jaffe, Andrew E.

    2016-01-01

    Differentiating pluripotent cells from fibroblast progenitors is a potentially transformative tool in personalized medicine. We previously identified relatively greater success culturing dura-derived fibroblasts than scalp-derived fibroblasts from postmortem tissue. We hypothesized that these differences in culture success were related to epigenetic differences between the cultured fibroblasts by sampling location, and therefore generated genome-wide DNA methylation and transcriptome data on 11 intrinsically matched pairs of dural and scalp fibroblasts from donors across the lifespan (infant to 85 years). While these cultured fibroblasts were several generations removed from the primary tissue and morphologically indistinguishable, we found widespread epigenetic differences by sampling location at the single CpG (N = 101,989), region (N = 697), “block” (N = 243), and global spatial scales suggesting a strong epigenetic memory of original fibroblast location. Furthermore, many of these epigenetic differences manifested in the transcriptome, particularly at the region-level. We further identified 7,265 CpGs and 11 regions showing significant epigenetic memory related to the age of the donor, as well as an overall increased epigenetic variability, preferentially in scalp-derived fibroblasts—83% of loci were more variable in scalp, hypothesized to result from cumulative exposure to environmental stimuli in the primary tissue. By integrating publicly available DNA methylation datasets on individual cell populations in blood and brain, we identified significantly increased inter-individual variability in our scalp- and other skin-derived fibroblasts on a similar scale as epigenetic differences between different lineages of blood cells. Lastly, these epigenetic differences did not appear to be driven by somatic mutation—while we identified 64 probable de-novo variants across the 11 subjects, there was no association between mutation burden and age of the donor (p = 0.71). These results depict a strong component of epigenetic memory in cell culture from primary tissue, even after several generations of daughter cells, related to cell state and donor age. PMID:26913521

  19. Identification of Novel Human Dipeptidyl Peptidase-IV Inhibitors of Natural Origin (Part II): In Silico Prediction in Antidiabetic Extracts

    PubMed Central

    Guasch, Laura; Sala, Esther; Ojeda, María José; Valls, Cristina; Bladé, Cinta; Mulero, Miquel; Blay, Mayte; Ardévol, Anna; Garcia-Vallvé, Santiago; Pujadas, Gerard

    2012-01-01

    Background Natural extracts play an important role in traditional medicines for the treatment of diabetes mellitus and are also an essential resource for new drug discovery. Dipeptidyl peptidase IV (DPP-IV) inhibitors are potential candidates for the treatment of type 2 diabetes mellitus, and the effectiveness of certain antidiabetic extracts of natural origin could be, at least partially, explained by the inhibition of DPP-IV. Methodology/Principal Findings Using an initial set of 29,779 natural products that are annotated with their natural source and an experimentally validated virtual screening procedure previously developed in our lab (Guasch et al.; 2012) [1], we have predicted 12 potential DPP-IV inhibitors from 12 different plant extracts that are known to have antidiabetic activity. Seven of these molecules are identical or similar to molecules with described antidiabetic activity (although their role as DPP-IV inhibitors has not been suggested as an explanation for their bioactivity). Therefore, it is plausible that these 12 molecules could be responsible, at least in part, for the antidiabetic activity of these extracts through their inhibitory effect on DPP-IV. In addition, we also identified as potential DPP-IV inhibitors 6 molecules from 6 different plants with no described antidiabetic activity but that share the same genus as plants with known antidiabetic properties. Moreover, none of the 18 molecules that we predicted as DPP-IV inhibitors exhibits chemical similarity with a group of 2,342 known DPP-IV inhibitors. Conclusions/Significance Our study identified 18 potential DPP-IV inhibitors in 18 different plant extracts (12 of these plants have known antidiabetic properties, whereas, for the remaining 6, antidiabetic activity has been reported for other plant species from the same genus). Moreover, none of the 18 molecules exhibits chemical similarity with a large group of known DPP-IV inhibitors. PMID:23028712

  20. Human microRNA-24 modulates highly pathogenic avian-origin H5N1 influenza A virus infection in A549 cells by targeting secretory pathway furin.

    PubMed

    Loveday, Emma-Kate; Diederich, Sandra; Pasick, John; Jean, François

    2015-01-01

    A common critical cellular event that many human enveloped viruses share is the requirement for proteolytic cleavage of the viral glycoprotein by furin in the host secretory pathway. For example, the furin-dependent proteolytic activation of highly pathogenic (HP) influenza A (infA) H5 and H7 haemagglutinin precursor (HA0) subtypes is critical for yielding fusion-competent infectious virions. In this study, we hypothesized that viral hijacking of the furin pathway by HP infA viruses to permit cleavage of HA0 could represent a novel molecular mechanism controlling the dynamic production of fusion-competent infectious virus particles during the viral life cycle. We explored the biological role of a newly identified furin-directed human microRNA, miR-24, in this process as a potential post-transcriptional regulator of the furin-mediated activation of HA0 and production of fusion-competent virions in the host secretory pathway. We report that miR-24 and furin are differentially expressed in human A549 cells infected with HP avian-origin infA H5N1. Using miR-24 mimics, we demonstrated a robust decrease in both furin mRNA levels and intracellular furin activity in A549 cells. Importantly, pretreatment of A549 cells with miR-24 mimicked these results: a robust decrease of H5N1 infectious virions and a complete block of H5N1 virus spread that was not observed in A549 cells infected with low-pathogenicity swine-origin infA H1N1 virus. Our results suggest that viral-specific downregulation of furin-directed microRNAs such as miR-24 during the life cycle of HP infA viruses may represent a novel regulatory mechanism that governs furin-mediated proteolytic activation of HA0 glycoproteins and production of infectious virions. PMID:25234642

  1. Identification of Novel Human Dipeptidyl Peptidase-IV Inhibitors of Natural Origin (Part I): Virtual Screening and Activity Assays

    PubMed Central

    Guasch, Laura; Ojeda, Maria José; González-Abuín, Noemí; Sala, Esther; Cereto-Massagué, Adrià; Mulero, Miquel; Valls, Cristina; Pinent, Montserrat; Ardévol, Anna; Garcia-Vallvé, Santiago; Pujadas, Gerard

    2012-01-01

    Background There has been great interest in determining whether natural products show biological activity toward protein targets of pharmacological relevance. One target of particular interest is DPP-IV whose most important substrates are incretins that, among other beneficial effects, stimulates insulin biosynthesis and secretion. Incretins have very short half-lives because of their rapid degradation by DPP-IV and, therefore, inhibiting this enzyme improves glucose homeostasis. As a result, DPP-IV inhibitors are of considerable interest to the pharmaceutical industry. The main goals of this study were (a) to develop a virtual screening process to identify potential DPP-IV inhibitors of natural origin; (b) to evaluate the reliability of our virtual-screening protocol by experimentally testing the in vitro activity of selected natural-product hits; and (c) to use the most active hit for predicting derivatives with higher binding affinities for the DPP-IV binding site. Methodology/Principal Findings We predicted that 446 out of the 89,165 molecules present in the natural products subset of the ZINC database would inhibit DPP-IV with good ADMET properties. Notably, when these 446 molecules were merged with 2,342 known DPP-IV inhibitors and the resulting set was classified into 50 clusters according to chemical similarity, there were 12 clusters that contained only natural products for which no DPP-IV inhibitory activity has been previously reported. Nine molecules from 7 of these 12 clusters were then selected for in vitro activity testing and 7 out of the 9 molecules were shown to inhibit DPP-IV (where the remaining two molecules could not be solubilized, preventing the evaluation of their DPP-IV inhibitory activity). Then, the hit with the highest activity was used as a lead compound in the prediction of more potent derivatives. Conclusions/Significance We have demonstrated that our virtual-screening protocol was successful in identifying novel lead compounds for developing more potent DPP-IV inhibitors. PMID:22984596

  2. Evidence for the evolutionary origin of human chromosome 21 from comparative gene mapping in the cow and mouse

    SciTech Connect

    Threadgill, D.S.; Womack, J.E. ); Kraus, J.P. ); Krawetz, S.A. )

    1991-01-01

    To determine the extent of conservation between bovine syntenic group U10, human chromosome 21 (HSA 21), and mouse chromosome 16(MMU 16), 11 genes were physically mapped by segregation analysis in a bovine-hamster hybrid somatic cell panel. The genes chosen for study span MMU 16 and represent virtually the entire q arm of HSA 21. Because the somatostatin gene (SST), an HSA 3/MMU 16 locus, was previously shown to be in U10, the transferrin gene (TF), an HSA 3/MMU 9 marker, was also mapped to determine whether U10 contains any HSA 3 genes not represented on MMU 16. With the exception of the protamine gene PRM1 (HSA 16/MMU 16), all of the genes studies were syntenic on bovine U10. Thus, all homologous loci from HSA 21 that have been studied in the cow are on a single chromosome. The bovine homolog of HSA 21 also carries several HSA 3 genes, two of which have homologous loci on MMU 16. The syntenic association of genes from the q arm of HSA 3 with HSAS 21 genes in two mammalian species, the mouse and the cow, indicates that HSA 21 may have evolved from a larger ancestral mammalian chromosome that contained genes now residing on HSA 3. Additionally, the syntenic association of TF with SST in the cow permits the prediction that the rhodopsin gene (RHO) is proximal to TF on HSA 3q.

  3. Evolutionary Ecology of Human Papillomavirus: Trade-offs, Coexistence, and Origins of High-Risk and Low-Risk Types

    PubMed Central

    Gatenby, Robert A.; Giuliano, Anna R.; Brown, Joel S.

    2012-01-01

    Background. We address the ecological and evolutionary dynamics of human papillomavirus (HPV) that lead to the dichotomy between high-risk (HR) and low-risk (LR) types. We hypothesize that HPV faces an evolutionary tradeoff between persistence and per-contact transmission probability. High virion production enhances transmissibility but also provokes an immune response leading to clearance and limited persistence. Alternatively, low virion production increases persistence at the cost of diminished transmission probability per sexual contact. We propose that LR HPV types use the former strategy and that HR types use the latter. Sexual behaviors in a host population determine the success of each strategy. Methods. We develop an evolutionary model of HPV epidemiology, which includes host sexual behavior, and we find evolutionarily stable strategies of HPV. Results. A slow turnover of sexual partners favors HR HPV, whereas high frequency of partner turnover selects for LR. When both sexual behaviors exist as subcultures in a population, disruptive selection can result in the coevolution and ecological coexistence of both HR and LR HPV types. Conclusions. Our results indicate that the elimination of HR HPV through vaccines may alter the evolutionary trajectory of the remaining types and promote evolution of new HR HPV types. PMID:22090448

  4. Detection of Intracellular Gene Expression in Live Cells of Murine, Human and Porcine Origin Using Fluorescence-labeled Nanoparticles

    PubMed Central

    Dreßen, Martina; Adamczyk, Klaudia; Deutsch, Marcus-André; Ulrich, Hanna; Schiemann, Matthias; Lange, Rüdiger; Krane, Markus

    2015-01-01

    The reprogramming of somatic cells to induced pluripotent stem cells (iPS) has successfully been performed in different mammalian species including mouse, rat, human, pig and others. The verification of iPS clones mainly relies on the detection of the endogenous expression of different pluripotency genes. These genes mostly represent transcription factors which are located in the cell nucleus. Traditionally, the proof of their endogenous expression is supplied by immunohistochemical staining after fixation of the cells. This approach requires replicate cultures of each clone at this early stage to preserve validated clones for further experiments. The present protocol describes an approach with gene-specific nanoparticles which allows the evaluation of intracellular gene expression directly in live cells by fluorescence. The nanoparticles consist of a central gold particle coupled to a capture strand carrying a sequence complementary to the target mRNA as well as a quenched reporter strand. These nanoparticles are actively endocytosed and the target mRNA displaces the reporter strand which then start to fluoresce. Therefore, specific target gene expression can be detected directly under the microscope. In addition, the emitted fluorescence allows the identification, isolation and enrichment of cells expressing a specific gene by flow cytometry. This method can be applied directly to live cells in culture without any manipulation of the target cells. PMID:26650934

  5. The view from down under: a test of the multiregional hypothesis of modern human origins using the basicranial evidence from Australasia.

    PubMed

    Durband, Arthur C

    2007-09-01

    Proponents of the Multiregional Hypothesis of modern human origins have consistently stated that Australasia provides one of the most compelling examples of regional continuity in the human fossil record. According to these workers, features found in the earliest Homo erectus fossils from Sangiran, Central Java, can be traced through more advanced hominids from Ngandong and are found in fossil and recent Australian Aborigines. In order to test the hypothesis that a close evolutionary relationship exists amongst the fossils from Australasia, this study will examine the cranial base. This region of the skull is considered to be evolutionarily conservative and has relatively good representation and preservation throughout much of the Australasian record. The results of this project highlight a number of features on the cranial base in the Ngandong sample that appear to be unique not only within the region, but in the human fossil sample as a whole. Several of these features, such as the morphology of the foramen ovale, the location of the squamotympanic fissure in the roof of the temporomandibular fossa, and the extreme expression of the postcondyloid tuberosities have been pointed out by workers such as Weidenreich and Jacob in their surveys of this material. The presence of these characters in the Ngandong population, and their apparent lack of expression outside of this group, provides strong evidence of discontinuity in the Australasian fossil record. PMID:18041369

  6. Cosmic ray variations of solar origin in relation to human physiological state during the December 2006 solar extreme events

    NASA Astrophysics Data System (ADS)

    Papailiou, M.; Mavromichalaki, H.; Vassilaki, A.; Kelesidis, K. M.; Mertzanos, G. A.; Petropoulos, B.

    2009-02-01

    There is an increasing amount of evidence linking biological effects to solar and geomagnetic disturbances. A series of studies is published referring to the changes in human physiological responses at different levels of geomagnetic activity. In this study, the possible relation between the daily variations of cosmic ray intensity, measured by the Neutron Monitor at the Cosmic Ray Station of the University of Athens (http://cosray.phys.uoa.gr) and the average daily and hourly heart rate variations of persons, with no symptoms or hospital admission, monitored by Holter electrocardiogram, is considered. This work refers to a group of persons admitted to the cardiological clinic of the KAT Hospital in Athens during the time period from 4th to 24th December 2006 that is characterized by extreme solar and geomagnetic activity. A series of Forbush decreases started on 6th December and lasted until the end of the month and a great solar proton event causing a Ground Level Enhancement (GLE) of the cosmic ray intensity on 13th December occurred. A sudden decrease of the cosmic ray intensity on 15th December, when a geomagnetic storm was registered, was also recorded in Athens Neutron Monitor station (cut-off rigidity 8.53 GV) with amplitude of 4%. It is noticed that during geomagnetically quiet days the heart rate and the cosmic ray intensity variations are positively correlated. When intense cosmic ray variations, like Forbush decreases and relativistic proton events produced by strong solar phenomena occur, cosmic ray intensity and heart rate get minimum values and their variations, also, coincide. During these events the correlation coefficient of these two parameters changes and follows the behavior of the cosmic ray intensity variations. This is only a small part of an extended investigation, which has begun using data from the year 2002 and is still in progress.

  7. Influence of Oxygen Tension on Dopaminergic Differentiation of Human Fetal Stem Cells of Midbrain and Forebrain Origin

    PubMed Central

    Krabbe, Christina; Bak, Sara Thornby; Jensen, Pia; von Linstow, Christian; Martínez Serrano, Alberto; Hansen, Claus; Meyer, Morten

    2014-01-01

    Neural stem cells (NSCs) constitute a promising source of cells for transplantation in Parkinson's disease (PD), but protocols for controlled dopaminergic differentiation are not yet available. Here we investigated the influence of oxygen on dopaminergic differentiation of human fetal NSCs derived from the midbrain and forebrain. Cells were differentiated for 10 days in vitro at low, physiological (3%) versus high, atmospheric (20%) oxygen tension. Low oxygen resulted in upregulation of vascular endothelial growth factor and increased the proportion of tyrosine hydroxylase-immunoreactive (TH-ir) cells in both types of cultures (midbrain: 9.1±0.5 and 17.1±0.4 (P<0.001); forebrain: 1.9±0.4 and 3.9±0.6 (P<0.01) percent of total cells). Regardless of oxygen levels, the content of TH-ir cells with mature neuronal morphologies was higher for midbrain as compared to forebrain cultures. Proliferative Ki67-ir cells were found in both types of cultures, but the relative proportion of these cells was significantly higher for forebrain NSCs cultured at low, as compared to high, oxygen tension. No such difference was detected for midbrain-derived cells. Western blot analysis revealed that low oxygen enhanced β-tubulin III and GFAP expression in both cultures. Up-regulation of β-tubulin III was most pronounced for midbrain cells, whereas GFAP expression was higher in forebrain as compared to midbrain cells. NSCs from both brain regions displayed less cell death when cultured at low oxygen tension. Following mictrotransplantation into mouse striatal slice cultures predifferentiated midbrain NSCs were found to proliferate and differentiate into substantial numbers of TH-ir neurons with mature neuronal morphologies, particularly at low oxygen. In contrast, predifferentiated forebrain NSCs microtransplanted using identical conditions displayed little proliferation and contained few TH-ir cells, all of which had an immature appearance. Our data may reflect differences in dopaminergic differentiation capacity and region-specific requirements of NSCs, with the dopamine-depleted striatum cultured at low oxygen offering an attractive micro-environment for midbrain NSCs. PMID:24788190

  8. Catarrhine phylogeny: noncoding DNA evidence for a diphyletic origin of the mangabeys and for a human-chimpanzee clade.

    PubMed

    Page, S L; Goodman, M

    2001-01-01

    Maximum-parsimony and maximum-likelihood analyses of two of the serum albumin gene's intron sequences from 24 catarrhines (17 cercopithecid and 7 hominid) and 3 platyrrhines (an outgroup to the catarrhines) yielded results on catarrhine phylogeny that are congruent with those obtained with noncoding sequences of the gamma(1)-gamma(2) globin gene genomic region, using only those flanking and intergenic gamma sequences that in their history were not involved in gene conversion. A data set that combined in a tandem alignment these two sets of noncoding DNA orthologues from the two unlinked nuclear genomic loci yielded the following confirmatory results both on the course of cladistic branchings (the divisions in a cladistic classification of higher ranking taxa into subordinate taxa) and on the ages of the taxa (each taxon representing a clade). The cercopithecid branch of catarrhines, at approximately 14 Ma (mega annum) divided into Colobini (the leaf-eating Old World monkeys) and Cercopithecini (the cheek-pouched Old World monkeys). At approximately 10-9 Ma, Colobini divided into an African clade, Colobina, and an Asian clade, Presbytina; similarly at this time level, Cercopithecini divided into Cercopithecina (the guenons, patas, and green monkeys) and Papionina. At approximately 7 Ma, Papionina divided into Macaca, Cercocebus, and Papio. At approximately 5 Ma, Cercocebus divided subgenerically into C. (Cercocebus) for terrestrial mangabeys and C. (Mandrillus) for drills and mandrills, while at approximately 4 Ma Papio divided subgenerically into P. (Locophocebus) for arboreal mangabeys, P. (Theropithecus) for gelada baboons, and P. (Papio) for hamadryas baboons. In turn, the hominid branch of catarrhines at approximately 18 Ma divided into Hylobatini (gibbons and siamangs) and Hominini; at approximately 14 Ma, Hominini divided into Pongina (orangutans) and Hominina; at approximately 7 Ma, Hominina divided into Gorilla and Homo; and at approximately 6-5 Ma, Homo divided subgenerically into H. (Homo) for humans and H. (Pan) for common and bonobo chimpanzees. Rates of noncoding DNA evolution were assessed using a data set of noncoding gamma sequence orthologues that represented 18 catarrhines, 16 platyrrhines, 3 non-anthropoid primates (2 tarsiers and 1 strepsirhine), and rabbit (as outgroup to the primates). Results obtained with this data set revealed a faster rate of nucleotide substitutions in the early primate lineage to the anthropoid (platyrrhine/catarrhine) ancestor than from that ancestor to the present. Rates were slower in catarrhines than in platyrrhines, slower in the cheek-pouched than in the leaf-eating cercopithecids, and slower yet in the hominids. On relating these results to data on brain sizes and life spans, it was suggested that life-history strategies that favor intelligence and longer life spans also select for decreases in de novo mutation rates. PMID:11161738

  9. [The origin and quality of water for human consumption: the health of the population residing in the Matanza-Riachuelo river basin area in Greater Buenos Aires].

    PubMed

    Monteverde, Malena; Cipponeri, Marcos; Angelaccio, Carlos; Gianuzzi, Leda

    2013-04-01

    The aim of this study is to analyze the origin and quality of water used for consumption in a sample of households in Matanza-Riachuelo river basin area in Greater Buenos Aires, Argentina. The results of drinking water by source indicated that 9% of water samples from the public water system, 45% of bottled water samples and 80% of well water samples were not safe for drinking due to excess content of coliforms, Escherichia coli or nitrates. Individuals living in households where well water is the main source of drinking water have a 55% higher chance of suffering a water-borne disease; in the cases of diarrheas, the probability is 87% higher and in the case of dermatitis, 160% higher. The water for human consumption in this region should be provided by centralized sources that assure control over the quality of the water. PMID:23680749

  10. A new algorithm to diagnose atrial ectopic origin from multi lead ECG systems--insights from 3D virtual human atria and torso.

    PubMed

    Alday, Erick A Perez; Colman, Michael A; Langley, Philip; Butters, Timothy D; Higham, Jonathan; Workman, Antony J; Hancox, Jules C; Zhang, Henggui

    2015-01-01

    Rapid atrial arrhythmias such as atrial fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose the early onset of AF in a cost-effective manner. The complex and rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atrial activation using the standard 12-lead ECG alone. Compared to conventional 12-lead ECG, more detailed ECG lead configurations may provide further information about spatio-temporal dynamics of the body surface potential (BSP) during atrial excitation. We apply a recently developed 3D human atrial model to simulate electrical activity during normal sinus rhythm and ectopic pacing. The atrial model is placed into a newly developed torso model which considers the presence of the lungs, liver and spinal cord. A boundary element method is used to compute the BSP resulting from atrial excitation. Elements of the torso mesh corresponding to the locations of the placement of the electrodes in the standard 12-lead and a more detailed 64-lead ECG configuration were selected. The ectopic focal activity was simulated at various origins across all the different regions of the atria. Simulated BSP maps during normal atrial excitation (i.e. sinoatrial node excitation) were compared to those observed experimentally (obtained from the 64-lead ECG system), showing a strong agreement between the evolution in time of the simulated and experimental data in the P-wave morphology of the ECG and dipole evolution. An algorithm to obtain the location of the stimulus from a 64-lead ECG system was developed. The algorithm presented had a success rate of 93%, meaning that it correctly identified the origin of atrial focus in 75/80 simulations, and involved a general approach relevant to any multi-lead ECG system. This represents a significant improvement over previously developed algorithms. PMID:25611350

  11. A New Algorithm to Diagnose Atrial Ectopic Origin from Multi Lead ECG Systems - Insights from 3D Virtual Human Atria and Torso

    PubMed Central

    Alday, Erick A. Perez; Colman, Michael A.; Langley, Philip; Butters, Timothy D.; Higham, Jonathan; Workman, Antony J.; Hancox, Jules C.; Zhang, Henggui

    2015-01-01

    Rapid atrial arrhythmias such as atrial fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose the early onset of AF in a cost-effective manner. The complex and rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atrial activation using the standard 12-lead ECG alone. Compared to conventional 12-lead ECG, more detailed ECG lead configurations may provide further information about spatio-temporal dynamics of the body surface potential (BSP) during atrial excitation. We apply a recently developed 3D human atrial model to simulate electrical activity during normal sinus rhythm and ectopic pacing. The atrial model is placed into a newly developed torso model which considers the presence of the lungs, liver and spinal cord. A boundary element method is used to compute the BSP resulting from atrial excitation. Elements of the torso mesh corresponding to the locations of the placement of the electrodes in the standard 12-lead and a more detailed 64-lead ECG configuration were selected. The ectopic focal activity was simulated at various origins across all the different regions of the atria. Simulated BSP maps during normal atrial excitation (i.e. sinoatrial node excitation) were compared to those observed experimentally (obtained from the 64-lead ECG system), showing a strong agreement between the evolution in time of the simulated and experimental data in the P-wave morphology of the ECG and dipole evolution. An algorithm to obtain the location of the stimulus from a 64-lead ECG system was developed. The algorithm presented had a success rate of 93%, meaning that it correctly identified the origin of atrial focus in 75/80 simulations, and involved a general approach relevant to any multi-lead ECG system. This represents a significant improvement over previously developed algorithms. PMID:25611350

  12. DNA methylation patterns in human tissues of uniparental origin using a zinc-Finger gene (ZNF127) from the Angelman/Prader-Willi region

    SciTech Connect

    Mowery-Rushton, P.A.; Surti, U.; Locker, J.

    1996-01-11

    In order to further our understanding of the epigenetic modification of DNA and its role in imprinting, we examined DNA methylation patterns of human tissues of uniparental origin. We used complete hydatidiform moles (CHM), which are totally androgenetic conceptions, to examine the paternal methylation pattern in the absence of a maternal contribution and we used ovarian teratomas to represent the maternal counterpart. We carried out an analysis of DNA methylation of a gene which has been shown to contain sites which are differentially methylated in a parent-specific fashion. The gene, ZNF127, is located on chromosome 15q11-q13 in the region associated with Prader-Willi and Angelman syndromes. The parent-of-origin DNA methylation has been postulated to reflect the presence of an imprint and recent studies have confirmed that ZNF127 is differentially expressed only from the paternal chromosome. We identified a unique pattern of hyper- and hypomethylated sites in androgenetic conceptions which was nearly identical to the paternal pattern found in sperm. This may represent the paternal germ-line methylation imprint. We also studied partial hydatidiform moles, non-molar triploid conceptions, normal chorionic villi, and somatic tissue. These all demonstrated a modified DNA methylation pattern characteristic of normal chorionic villi with only limited findings of the imprint. Our results suggest that human androgenetic conceptions may provide an excellent model to analyze epigenetic DNA modifications, such as methylation, in imprinted genes. The paternal allele-specific methylation imprint will also be useful clinically to confirm the androgenetic nature of suspected molar conceptions in which parental blood samples may not be available. 55 refs., 3 figs.

  13. Origin and prevalence of human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) among indigenous populations in the Americas.

    PubMed

    Paiva, Arthur; Casseb, Jorge

    2015-01-01

    Human T-lymphotropic virus type 1 (HTLV-1) is found in indigenous peoples of the Pacific Islands and the Americas, whereas type 2 (HTLV-2) is widely distributed among the indigenous peoples of the Americas, where it appears to be more prevalent than HTLV-1, and in some tribes of Central Africa. HTLV-2 is considered ancestral in the Americas and is transmitted to the general population and injection drug users from the indigenous population. In the Americas, HTLV-1 has more than one origin, being brought by immigrants in the Paleolithic period through the Bering Strait, through slave trade during the colonial period, and through Japanese immigration from the early 20th century, whereas HTLV-2 was only brought by immigrants through the Bering Strait. The endemicity of HTLV-2 among the indigenous people of Brazil makes the Brazilian Amazon the largest endemic area in the world for its occurrence. A review of HTLV-1 in all Brazilian tribes supports the African origin of HTLV-1 in Brazil. The risk of hyperendemicity in these epidemiologically closed populations and transmission to other populations reinforces the importance of public health interventions for HTLV control, including the recognition of the infection among reportable diseases and events. PMID:25651320

  14. ORIGIN AND PREVALENCE OF HUMAN T-LYMPHOTROPIC VIRUS TYPE 1 (HTLV-1) AND TYPE 2 (HTLV-2) AMONG INDIGENOUS POPULATIONS IN THE AMERICAS

    PubMed Central

    Paiva, Arthur; Casseb, Jorge

    2015-01-01

    Human T-lymphotropic virus type 1 (HTLV-1) is found in indigenous peoples of the Pacific Islands and the Americas, whereas type 2 (HTLV-2) is widely distributed among the indigenous peoples of the Americas, where it appears to be more prevalent than HTLV-1, and in some tribes of Central Africa. HTLV-2 is considered ancestral in the Americas and is transmitted to the general population and injection drug users from the indigenous population. In the Americas, HTLV-1 has more than one origin, being brought by immigrants in the Paleolithic period through the Bering Strait, through slave trade during the colonial period, and through Japanese immigration from the early 20th century, whereas HTLV-2 was only brought by immigrants through the Bering Strait. The endemicity of HTLV-2 among the indigenous people of Brazil makes the Brazilian Amazon the largest endemic area in the world for its occurrence. A review of HTLV-1 in all Brazilian tribes supports the African origin of HTLV-1 in Brazil. The risk of hyperendemicity in these epidemiologically closed populations and transmission to other populations reinforces the importance of public health interventions for HTLV control, including the recognition of the infection among reportable diseases and events. PMID:25651320

  15. Original Misunderstanding

    ERIC Educational Resources Information Center

    Holtzman, Alexander

    2009-01-01

    Humorist Josh Billings quipped, "About the most originality that any writer can hope to achieve honestly is to steal with good judgment." Billings was harsh in his view of originality, but his critique reveals a tension faced by students every time they write a history paper. Research is the essence of any history paper. Especially in high school,…

  16. A Lactobacillus acidophilus strain of human gastrointestinal microbiota origin elicits killing of enterovirulent Salmonella enterica Serovar Typhimurium by triggering lethal bacterial membrane damage.

    PubMed

    Coconnier-Polter, Marie-Hélène; Liévin-Le Moal, Vanessa; Servin, Alain L

    2005-10-01

    The human gastrointestinal microbiota produces antagonistic activities against gastrointestinal bacterial pathogens. We undertook a study to investigate the mechanism(s) by which a Lactobacillus acidophilus strain of human microbiota origin antagonizes the gram-negative enteroinvasive pathogen Salmonella enterica serovar Typhimurium. We showed that the cell-free culture supernatant of L. acidophilus strain LB (LB-CFCS) induced the following effects in S. enterica SL1344: (i) a decrease in intracellular ATP that paralleled bacterial death, (ii) the release of lipopolysaccharide, (iii) permeabilization of the bacterial membrane, and (iv) an increase in the sensitivity of Salmonella to the lytic action of sodium dodecyl sulfate. Finally, we showed using two mutant strains of Salmonella, PhoP MS7953s and PmrA JKS1170, that the two-component regulatory systems PhoP-PhoQ and PmrA-PmrB that regulate the mechanisms of resistance to antibacterial agents in Salmonella did not influence the anti-Salmonella effect of LB-CFCS. PMID:16204528

  17. Orc1 Binding to Mitotic Chromosomes Precedes Spatial Patterning during G1 Phase and Assembly of the Origin Recognition Complex in Human Cells.

    PubMed

    Kara, Nihan; Hossain, Manzar; Prasanth, Supriya G; Stillman, Bruce

    2015-05-01

    Replication of eukaryotic chromosomes occurs once every cell division cycle in normal cells and is a tightly controlled process that ensures complete genome duplication. The origin recognition complex (ORC) plays a key role during the initiation of DNA replication. In human cells, the level of Orc1, the largest subunit of ORC, is regulated during the cell division cycle, and thus ORC is a dynamic complex. Upon S phase entry, Orc1 is ubiquitinated and targeted for destruction, with subsequent dissociation of ORC from chromosomes. Time lapse and live cell images of human cells expressing fluorescently tagged Orc1 show that Orc1 re-localizes to condensing chromatin during early mitosis and then displays different nuclear localization patterns at different times during G1 phase, remaining associated with late replicating regions of the genome in late G1 phase. The initial binding of Orc1 to mitotic chromosomes requires C-terminal amino acid sequences that are similar to mitotic chromosome-binding sequences in the transcriptional pioneer protein FOXA1. Depletion of Orc1 causes concomitant loss of the mini-chromosome maintenance (Mcm2-7) helicase proteins on chromatin. The data suggest that Orc1 acts as a nucleating center for ORC assembly and then pre-replication complex assembly by binding to mitotic chromosomes, followed by gradual removal from chromatin during the G1 phase. PMID:25784553

  18. Landmarks in the Evolution of (t)-RNAs from the Origin of Life up to Their Present Role in Human Cognition

    PubMed Central

    Balke, Darko; Kuss, Andreas; Müller, Sabine

    2015-01-01

    How could modern life have evolved? The answer to that question still remains unclear. However, evidence is growing that, since the origin of life, RNA could have played an important role throughout evolution, right up to the development of complex organisms and even highly sophisticated features such as human cognition. RNA mediated RNA-aminoacylation can be seen as a first landmark on the path from the RNA world to modern DNA- and protein-based life. Likewise, the generation of the RNA modifications that can be found in various RNA species today may already have started in the RNA world, where such modifications most likely entailed functional advantages. This association of modification patterns with functional features was apparently maintained throughout the further course of evolution, and particularly tRNAs can now be seen as paradigms for the developing interdependence between structure, modification and function. It is in this spirit that this review highlights important stepping stones of the development of (t)RNAs and their modifications (including aminoacylation) from the ancient RNA world up until their present role in the development and maintenance of human cognition. The latter can be seen as a high point of evolution at its present stage, and the susceptibility of cognitive features to even small alterations in the proper structure and functioning of tRNAs underscores the evolutionary relevance of this RNA species. PMID:26703740

  19. Human Mesenchymal Stem Cells of Diverse Origins Support Persistent Infection with Kaposi’s Sarcoma-Associated Herpesvirus and Manifest Distinct Angiogenic, Invasive, and Transforming Phenotypes

    PubMed Central

    Lee, Myung-Shin; Yuan, Hongfeng; Jeon, Hyungtaek; Zhu, Ying; Yoo, Seungmin; Shi, Songtao; Krueger, Brian; Renne, Rolf; Lu, Chun; Jung, Jae U.

    2016-01-01

    ABSTRACT Kaposi’s sarcoma (KS), a highly angiogenic and invasive tumor often involving different organ sites, including the oral cavity, is caused by infection with Kaposi’s sarcoma-associated herpesvirus (KSHV). Diverse cell markers have been identified on KS tumor cells, but their origin remains an enigma. We previously showed that KSHV could efficiently infect, transform, and reprogram rat primary mesenchymal stem cells (MSCs) into KS-like tumor cells. In this study, we showed that human primary MSCs derived from diverse organs, including bone marrow (MSCbm), adipose tissue (MSCa), dental pulp, gingiva tissue (GMSC), and exfoliated deciduous teeth, were permissive to KSHV infection. We successfully established long-term cultures of KSHV-infected MSCa, MSCbm, and GMSC (LTC-KMSCs). While LTC-KMSCs had lower proliferation rates than the uninfected cells, they expressed mixtures of KS markers and displayed differential angiogenic, invasive, and transforming phenotypes. Genetic analysis identified KSHV-derived microRNAs that mediated KSHV-induced angiogenic activity by activating the AKT pathway. These results indicated that human MSCs could be the KSHV target cells in vivo and established valid models for delineating the mechanism of KSHV infection, replication, and malignant transformation in biologically relevant cell types. PMID:26814175

  20. Landmarks in the Evolution of (t)-RNAs from the Origin of Life up to Their Present Role in Human Cognition.

    PubMed

    Balke, Darko; Kuss, Andreas; Müller, Sabine

    2015-01-01

    How could modern life have evolved? The answer to that question still remains unclear. However, evidence is growing that, since the origin of life, RNA could have played an important role throughout evolution, right up to the development of complex organisms and even highly sophisticated features such as human cognition. RNA mediated RNA-aminoacylation can be seen as a first landmark on the path from the RNA world to modern DNA- and protein-based life. Likewise, the generation of the RNA modifications that can be found in various RNA species today may already have started in the RNA world, where such modifications most likely entailed functional advantages. This association of modification patterns with functional features was apparently maintained throughout the further course of evolution, and particularly tRNAs can now be seen as paradigms for the developing interdependence between structure, modification and function. It is in this spirit that this review highlights important stepping stones of the development of (t)RNAs and their modifications (including aminoacylation) from the ancient RNA world up until their present role in the development and maintenance of human cognition. The latter can be seen as a high point of evolution at its present stage, and the susceptibility of cognitive features to even small alterations in the proper structure and functioning of tRNAs underscores the evolutionary relevance of this RNA species. PMID:26703740

  1. Analysis of the expression of the 4F2 surface antigen in normal and neoplastic fibroblastic human cells of embryonic and adult origin.

    PubMed

    Azzarone, B; Malpièce, Y; Zaech, P; Moretta, L; Fauci, A; Suarez, H

    1985-08-01

    4F2 monoclonal antibody recognizes a 120-kD glycoprotein on the surface of human spread fibroblastic cells of embryonic and neoplastic origin, but it does not bind to normal spread adult fibroblasts. Flow cytometric analysis reveals that human adult fibroblasts become 4F2-positive when they are analyzed as round-shaped cells; this means that, in normal adult cells, 4F2 antigen behaves as a cryptic molecule. Thus, the basic difference between embryonic, neoplastic and normal adult cells consists in a different organization in the architecture of the cell membrane, since in embryonic and neoplastic cells there is a continuous expression of the 4F2 antigen independently of the cell shape and cell cycle phase. Quantitative flow cytometry shows that the mean surface density (MSD) of the 4F2 antigen 1, does not vary as a function of the cell cycle; 2, is inversely related to cell size and "metabolic time". This suggests that at the plateau phase the surface organization of G1 resting cells changes as a function of the number of days spent in culture; and 3, sarcoma and SV40-transformed cells show significantly increased MSD levels of the 4F2 antigen in comparison with normal cells of similar size. Electrophoretic analysis under reducing conditions confirms the quantitative differences in the expression of the 4F2 antigen described with the cell sorter. It also reveals, in a way different from that previously found with lymphoid cells, the coexistence of two molecules (85 and 73 kD) in the heavy chain regions. The 73 kD is, however, much more strongly expressed in the fibrosarcoma than in the embryonic cells. Finally, it shows that 4F2 antigen is a very useful tool for studying the organization and the structure of the cell membrane of human fibroblasts and can provide new insights to understand better the developmental and transformation processes. PMID:4029274

  2. The Origin of Malignant Malaria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasmodium falciparum is the causative agent of malignant malaria, which is among the most severe human infectious diseases. Despite its overwhelming significance to human health, the parasite’s origins remain unclear. The favored origin hypothesis holds that P. falciparum and its closest known rel...

  3. On the origin of lipofuscin; the iron content of residual bodies, and the relation of these organelles to the lysosomal vacuome. A study on cultured human glial cells

    SciTech Connect

    Brunk, U.T. )

    1989-01-01

    Cultured human glial cells constitute a suitable model system for the study of lipofuscinogenesis in vitro. These cells, although not post-mitotic, can be kept for several months in stable monolayers due to their display of very pronounced density-dependent inhibition of cell growth. Residual bodies, or lipofuscin pigment granules, accumulate over time in this pseudo post-mitotic cell system. I. In early dense cultures, exposed to purified rat liver mitochondriae, it was possible to follow the uptake of mitochondriae and their degradation, which was found to be incomplete and result in the formation of numerous residual bodies containing lipofuscin-type material. It was concluded that incomplete degradation of mitochondriae may be an important origin of lipofuscin. II. Dense, older cultures exposed to electron dense marker particles (colloidal thorium dioxide) accumulated these markers within endosomes, and later in secondary lysosomes of various types, including residual bodies. It was concluded that residual bodies constitute an integral part of the lysosomal vacuome system. III. Phase III glial cells were cultured on formvar-coated gold EM-grids and studied by whole cell transmission electron microscopy using TEM and STEM techniques in combination with energy dispersive X-ray microanalysis. It was found that residual bodies contained iron. This fact was taken as a further indication that lipofuscin has its origin in autophagocytosed mitochondriae and ER-material rich in metallo-enzymes. Due to their high concentration of iron, residual bodies may constitute unstable structures within the cells. Since iron is a well known catalyst of various peroxidative processes, the surrounding lysosomal membrane might be damaged, e.g. by oxidative stress, with risk for leakage of degradative lysosomal enzymes into the cell sap.

  4. Remodeling of the Human Papillomavirus Type 11 Replication Origin into Discrete Nucleoprotein Particles and Looped Structures by the E2 Protein

    PubMed Central

    Sim, Jeonggu; Ozgur, Sezgin; Lin, Biing Yuan; Yu, Jei-Hwa; Broker, Thomas R.; Chow, Louise T.; Griffith, Jack

    2009-01-01

    The human papillomavirus (HPV) origin (ori) of DNA replication shares a common theme with many DNA control elements in having multiple binding sites for one or more proteins spaced over several hundred base pairs. The HPV type-11 ori spans 103 bp and contains three palindromic binding sites (E2BS-2, E2BS-3, and E2BS-4) for the dimeric E2 origin binding protein. These sites are separated by 64 bp and 3 bp. E2BS-1 is located 288 bp upstream of E2BS-2 and is not required for efficient transient or cell-free replication. In this study, electron microscopy was used to visualize complexes of HPV-11 ori DNA bound by purified E2 protein. DNA containing only E2BS-2 showed a single E2 dimer bound. DNA containing E2BS-3 and E2BS-4 showed two side-by-side E2 dimers, while DNA containing E2BS-2, E2BS-3, and E2BS-4 exhibited a large disk/ring-shaped protein particle bound indicating that the DNA had been remodeled into a discrete complex, likely containing an E2 hexamer. With all four binding sites present, up to 27% of the DNA molecules were arranged into loops by E2, the majority of which spanned E2BS-1 and one of the other three sites. Studies of the dependence of looping on salt, ATP, and DTT using full length E2 and an E2 protein containing only the carboxyl-terminal DNA binding and protein dimerization domain suggest that looping is dependent on the N terminal domain as well as factors which may affect the manner in which E2 scans DNA for binding sites. The role of these structures in the modeling and regulation of the HPV-11 ori is discussed. PMID:18067922

  5. Isolation of Cancer Stem Like Cells from Human Adenosquamous Carcinoma of the Lung Supports a Monoclonal Origin from a Multipotential Tissue Stem Cell

    PubMed Central

    Mather, Jennie P.; Roberts, Penelope E.; Pan, Zhuangyu; Chen, Francine; Hooley, Jeffrey; Young, Peter; Xu, Xiaolin; Smith, Douglas H.; Easton, Ann; Li, Panjing; Bonvini, Ezio; Koenig, Scott; Moore, Paul A.

    2013-01-01

    There is increasing evidence that many solid tumors are hierarchically organized with the bulk tumor cells having limited replication potential, but are sustained by a stem-like cell that perpetuates the tumor. These cancer stem cells have been hypothesized to originate from transformation of adult tissue stem cells, or through re-acquisition of stem-like properties by progenitor cells. Adenosquamous carcinoma (ASC) is an aggressive type of lung cancer that contains a mixture of cells with squamous (cytokeratin 5+) and adenocarcinoma (cytokeratin 7+) phenotypes. The origin of these mixtures is unclear as squamous carcinomas are thought to arise from basal cells in the upper respiratory tract while adenocarcinomas are believed to form from stem cells in the bronchial alveolar junction. We have isolated and characterized cancer stem-like populations from ASC through application of selective defined culture medium initially used to grow human lung stem cells. Homogeneous cells selected from ASC tumor specimens were stably expanded in vitro. Primary xenografts and metastatic lesions derived from these cells in NSG mice fully recapitulate both the adenocarcinoma and squamous features of the patient tumor. Interestingly, while the CSLC all co-expressed cytokeratins 5 and 7, most xenograft cells expressed either one, or neither, with <10% remaining double positive. We also demonstrated the potential of the CSLC to differentiate to multi-lineage structures with branching lung morphology expressing bronchial, alveolar and neuroendocrine markers in vitro. Taken together the properties of these ASC-derived CSLC suggests that ASC may arise from a primitive lung stem cell distinct from the bronchial-alveolar or basal stem cells. PMID:24324581

  6. The heterosexual human immunodeficiency virus type 1 epidemic in Thailand is caused by an intersubtype (A/E) recombinant of African origin.

    PubMed Central

    Gao, F; Robertson, D L; Morrison, S G; Hui, H; Craig, S; Decker, J; Fultz, P N; Girard, M; Shaw, G M; Hahn, B H; Sharp, P M

    1996-01-01

    Since 1989, human immunodeficiency virus type 1 (HIV-1) has spread explosively through the heterosexual population in Thailand. This epidemic is caused primarily by viruses classified as "subtype E", which, on the basis of limited sequence comparisons, appear to represent hybrids of subtypes A (gag) and E (env). However, the true evolutionary origins of "subtype E" viruses are still obscure since no complete genomes have been analyzed, and only one full-length subtype A sequence has been available for phylogenetic comparison. In this study, we determined full-length proviral sequences for "subtype E" viruses from Thailand (93TH253) and the Central African Republic (90CR402) and for a subtype A virus from Uganda (92UG037). We also sequenced the long terminal repeat (LTR) regions from 16 virus strains representing clades A, C, E, F, and G. Detailed phylogenetic analyses of these sequences indicated that "subtype E" viruses do indeed represent A/E recombinants with multiple points of crossover along their genomes. The extracellular portion of env, parts of vif and vpr, as well as most of the LTR are of subtype E origin, whereas the remainder of the genome is of subtype A origin. The possibility that the discordant phylogenetic positions of "subtype E" viruses in gag- and env-derived trees are the result of unusual rates or patterns of evolution was also considered but was ruled out on the basis of two lines of evidence: (i) phylogenetic trees constructed for synonymous and nonsynonymous substitutions yielded the same discordant branching orders for "subtype E" gag and env gene sequences, thus excluding selection-driven evolution, and (ii) multiple crossovers in the viral genome are most consistent with the copy choice model of recombination and have been observed in other documented examples of HIV-1 intersubtype recombination. Thai and CAR "subtype E" viruses exhibited the same pattern of A/E mosaicism, indicating that the recombination event occurred in Africa prior to the spread of virus to Asia. Finally, all "subtype E" viruses were found to contain a distinctive two-nucleotide bulge in their transactivation response (TAR) elements. This feature was present only in viruses which also contained a subtype A 5' pol region (i.e., subtype A viruses or A/D and A/E recombinants), raising the possibility of a functional linkage between the TAR region and the polymerase. The implications of epidemic spread of a recombinant HIV-1 strain to viral natural history and vaccine development are discussed. PMID:8794346

  7. A point mutation in the polymerase protein PB2 allows a reassortant H9N2 influenza isolate of wild-bird origin to replicate in human cells.

    PubMed

    Hussein, Islam T M; Ma, Eric J; Hill, Nichola J; Meixell, Brandt W; Lindberg, Mark; Albrecht, Randy A; Bahl, Justin; Runstadler, Jonathan A

    2016-07-01

    H9N2 influenza A viruses are on the list of potentially pandemic subtypes. Therefore, it is important to understand how genomic reassortment and genetic polymorphisms affect phenotypes of H9N2 viruses circulating in the wild bird reservoir. A comparative genetic analysis of North American H9N2 isolates of wild bird origin identified a naturally occurring reassortant virus containing gene segments derived from both North American and Eurasian lineage ancestors. The PB2 segment of this virus encodes 10 amino acid changes that distinguish it from other H9 strains circulating in North America. G590S, one of the 10 amino acid substitutions observed, was present in ~12% of H9 viruses worldwide. This mutation combined with R591 has been reported as a marker of pathogenicity for human pandemic 2009 H1N1 viruses. Screening by polymerase reporter assay of all the natural polymorphisms at these two positions identified G590/K591 and S590/K591 as the most active, with the highest polymerase activity recorded for the SK polymorphism. Rescued viruses containing these two polymorphic combinations replicated more efficiently in MDCK cells and they were the only ones tested that were capable of establishing productive infection in NHBE cells. A global analysis of all PB2 sequences identified the K591 signature in six viral HA/NA subtypes isolated from several hosts in seven geographic locations. Interestingly, introducing the K591 mutation into the PB2 of a human-adapted H3N2 virus did not affect its polymerase activity. Our findings demonstrate that a single point mutation in the PB2 of a low pathogenic H9N2 isolate could have a significant effect on viral phenotype and increase its propensity to infect mammals. However, this effect is not universal, warranting caution in interpreting point mutations without considering protein sequence context. PMID:27101787

  8. Colonization pattern of C. jejuni isolates of human and avian origin and differences in the induction of immune responses in chicken.

    PubMed

    Pielsticker, Colin; Glünder, Gerhard; Aung, Ye' Htut; Rautenschlein, Silke

    2016-01-01

    Campylobacter jejuni (C. jejuni) is the most frequently reported bacterial food-borne pathogen. Poultry is regarded to be the main reservoir for human campylobacteriosis. By some authors C. jejuni is considered as a commensal of the chicken gut, but clinical signs may be observed indicating host-pathogen interaction. Little is known about C. jejuni strain dependent differences in stimulation of the immune response in chicken. Therefore we investigated the colonization pattern as well as humoral and cell-mediated immune parameters in three-week old specific pathogen-free (SPF) layer-type (LT) chicken after inoculation with different human and avian derived C. jejuni isolates between three and 21dpi. In a subsequent experiment we investigated earlier time points and additionally compared commercial broilers with SPF-LT chicken to identify possible differences after inoculation of selected C. jejuni strains from prior experiments. No clinical symptoms were observed during the experiments. The colonization pattern did not correlate with the strain origin or magnitude of circulating C. jejuni specific antibodies. Only minor changes were observed in caecal T cell populations after C. jejuni inoculation compared to non-inoculated controls. Interestingly the mRNA expression of IL-6 and IFN-gamma was down regulated at some time points after inoculation suggesting a possible immunomodulatory effect of some C. jejuni strains in the gut. Furthermore, broilers were colonized to a higher extend and the local immune cell response was different compared to the SPF -LT birds indicating an influence of genotype on C. jejuni colonization pattern. Overall, our study demonstrates that the outcome of C. jejuni infection in chicken is influenced by genotype and partially by the C. jejuni isolate, leading to differences in the early immune response and thereafter the control of colonization and infection. PMID:26827832

  9. Requirement of T-lymphokine-activated killer cell-originated protein kinase for TRAIL resistance of human HeLa cervical cancer cells

    SciTech Connect

    Kwon, Hyeok-Ran; Lee, Ki Won; Dong, Zigang; Lee, Kyung Bok; Oh, Sang-Muk

    2010-01-01

    T-lymphokine-activated killer cell-originated protein kinase (TOPK) appears to be highly expressed in various cancer cells and to play an important role in maintaining proliferation of cancer cells. However, the underlying mechanism by which TOPK regulates growth of cancer cells remains elusive. Here we report that upregulated endogenous TOPK augments resistance of cancer cells to apoptosis induced by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). Stable knocking down of TOPK markedly increased TRAIL-mediated apoptosis of human HeLa cervical cancer cells, as compared with control cells. Caspase 8 or caspase 3 activities in response to TRAIL were greatly incremented in TOPK-depleted cells. Ablation of TOPK negatively regulated TRAIL-mediated NF-{kappa}B activity. Furthermore, expression of NF-{kappa}B-dependent genes, FLICE-inhibitory protein (FLIP), inhibitor of apoptosis protein 1 (c-IAP1), or X-linked inhibitor of apoptosis protein (XIAP) was reduced in TOPK-depleted cells. Collectively, these findings demonstrated that TOPK contributed to TRAIL resistance of cancer cells via NF-{kappa}B activity, suggesting that TOPK might be a potential molecular target for successful cancer therapy using TRAIL.

  10. Slipping through the Cracks: The Taxonomic Impediment Conceals the Origin and Dispersal of Haminoea japonica, an Invasive Species with Impacts to Human Health

    PubMed Central

    Hanson, Dieta; Cooke, Samantha; Hirano, Yayoi; Malaquias, Manuel A. E.; Crocetta, Fabio; Valdés, Ángel

    2013-01-01

    Haminoea japonica is a species of opisthobranch sea slug native to Japan and Korea. Non-native populations have spread unnoticed for decades due to difficulties in the taxonomy of Haminoea species. Haminoea japonica is associated with a schistosome parasite in San Francisco Bay, thus further spread could have consequence to human health and economies. Anecdotal evidence suggests that H. japonica has displaced native species of Haminoea in North America and Europe, becoming locally dominant in estuaries and coastal lagoons. In this paper we study the population genetics of native and non-native populations of H. japonica based on mt-DNA data including newly discovered populations in Italy and France. The conclusions of this study further corroborate a Northeastern Japan origin for the non-native populations and suggest possible independent introductions into North America and Europe. Additionally, the data obtained revealed possible secondary introductions within Japan. Although non-native populations have experienced severe genetic bottlenecks they have colonized different regions with a broad range of water temperatures and other environmental conditions. The environmental tolerance of this species, along with its ability to become dominant in invaded areas and its association with a schistosome parasite, suggest H. japonica could be a dangerous invasive species. PMID:24098588

  11. Comparative Evaluation of Human Mesenchymal Stem Cells of Fetal (Wharton's Jelly) and Adult (Adipose Tissue) Origin during Prolonged In Vitro Expansion: Considerations for Cytotherapy

    PubMed Central

    Christodoulou, I.; Kolisis, F. N.; Papaevangeliou, D.; Zoumpourlis, V.

    2013-01-01

    Mesenchymal stem cells (MSCs) are somatic cells with a dual capacity for self-renewal and differentiation, and diverse therapeutic applicability, both experimentally and in the clinic. These cells can be isolated from various human tissues that may differ anatomically or developmentally with relative ease. Heterogeneity due to biological origin or in vitro manipulation is, nevertheless, considerable and may equate to differences in qualitative and quantitative characteristics which can prove crucial for successful therapeutic use. With this in mind, in the present study we have evaluated the proliferation kinetics and phenotypic characteristics of MSCs derived from two abundant sources, that is, fetal umbilical cord matrix (Wharton's jelly) and adult adipose tissue (termed WJSC and ADSC, resp.) during prolonged in vitro expansion, a process necessary for obtaining cell numbers sufficient for clinical application. Our results show that WJSC are derived with relatively high efficiency and bear a substantially increased proliferation capacity whilst largely sustaining the expression of typical immunophenotypic markers, whereas ADSC exhibit a reduced proliferation potential showing typical signs of senescence at an early stage. By combining kinetic with phenotypic data we identify culture thresholds up to which both cell types maintain their stem properties, and we discuss the practical implications of their differences. PMID:23533440

  12. Ubiquitous human ‘master’ origins of replication are encoded in the DNA sequence via a local enrichment in nucleosome excluding energy barriers

    NASA Astrophysics Data System (ADS)

    Drillon, Guénola; Audit, Benjamin; Argoul, Françoise; Arneodo, Alain

    2015-02-01

    As the elementary building block of eukaryotic chromatin, the nucleosome is at the heart of the compromise between the necessity of compacting DNA in the cell nucleus and the required accessibility to regulatory proteins. The recent availability of genome-wide experimental maps of nucleosome positions for many different organisms and cell types has provided an unprecedented opportunity to elucidate to what extent the DNA sequence conditions the primary structure of chromatin and in turn participates in the chromatin-mediated regulation of nuclear functions, such as gene expression and DNA replication. In this study, we use in vivo and in vitro genome-wide nucleosome occupancy data together with the set of nucleosome-free regions (NFRs) predicted by a physical model of nucleosome formation based on sequence-dependent bending properties of the DNA double-helix, to investigate the role of intrinsic nucleosome occupancy in the regulation of the replication spatio-temporal programme in human. We focus our analysis on the so-called replication U/N-domains that were shown to cover about half of the human genome in the germline (skew-N domains) as well as in embryonic stem cells, somatic and HeLa cells (mean replication timing U-domains). The ‘master’ origins of replication (MaOris) that border these megabase-sized U/N-domains were found to be specified by a few hundred kb wide regions that are hyper-sensitive to DNase I cleavage, hypomethylated, and enriched in epigenetic marks involved in transcription regulation, the hallmarks of localized open chromatin structures. Here we show that replication U/N-domain borders that are conserved in all considered cell lines have an environment highly enriched in nucleosome-excluding-energy barriers, suggesting that these ubiquitous MaOris have been selected during evolution. In contrast, MaOris that are cell-type-specific are mainly regulated epigenetically and are no longer favoured by a local abundance of intrinsic NFRs encoded in the DNA sequence. At the smaller few hundred bp scale of gene promoters, CpG-rich promoters of housekeeping genes found nearby ubiquitous MaOris as well as CpG-poor promoters of tissue-specific genes found nearby cell-type-specific MaOris, both correspond to in vivo NFRs that are not coded as nucleosome-excluding-energy barriers. Whereas the former promoters are likely to correspond to high occupancy transcription factor binding regions, the latter are an illustration that gene regulation in human is typically cell-type-specific.

  13. Ubiquitous human 'master' origins of replication are encoded in the DNA sequence via a local enrichment in nucleosome excluding energy barriers.

    PubMed

    Drillon, Guénola; Audit, Benjamin; Argoul, Françoise; Arneodo, Alain

    2015-02-18

    As the elementary building block of eukaryotic chromatin, the nucleosome is at the heart of the compromise between the necessity of compacting DNA in the cell nucleus and the required accessibility to regulatory proteins. The recent availability of genome-wide experimental maps of nucleosome positions for many different organisms and cell types has provided an unprecedented opportunity to elucidate to what extent the DNA sequence conditions the primary structure of chromatin and in turn participates in the chromatin-mediated regulation of nuclear functions, such as gene expression and DNA replication. In this study, we use in vivo and in vitro genome-wide nucleosome occupancy data together with the set of nucleosome-free regions (NFRs) predicted by a physical model of nucleosome formation based on sequence-dependent bending properties of the DNA double-helix, to investigate the role of intrinsic nucleosome occupancy in the regulation of the replication spatio-temporal programme in human. We focus our analysis on the so-called replication U/N-domains that were shown to cover about half of the human genome in the germline (skew-N domains) as well as in embryonic stem cells, somatic and HeLa cells (mean replication timing U-domains). The 'master' origins of replication (MaOris) that border these megabase-sized U/N-domains were found to be specified by a few hundred kb wide regions that are hyper-sensitive to DNase I cleavage, hypomethylated, and enriched in epigenetic marks involved in transcription regulation, the hallmarks of localized open chromatin structures. Here we show that replication U/N-domain borders that are conserved in all considered cell lines have an environment highly enriched in nucleosome-excluding-energy barriers, suggesting that these ubiquitous MaOris have been selected during evolution. In contrast, MaOris that are cell-type-specific are mainly regulated epigenetically and are no longer favoured by a local abundance of intrinsic NFRs encoded in the DNA sequence. At the smaller few hundred bp scale of gene promoters, CpG-rich promoters of housekeeping genes found nearby ubiquitous MaOris as well as CpG-poor promoters of tissue-specific genes found nearby cell-type-specific MaOris, both correspond to in vivo NFRs that are not coded as nucleosome-excluding-energy barriers. Whereas the former promoters are likely to correspond to high occupancy transcription factor binding regions, the latter are an illustration that gene regulation in human is typically cell-type-specific. PMID:25563930

  14. Original Version

    Cancer.gov

    The EPEC-O (Education in Palliative and End-of-Life Care for Oncology) Self-Study Original Version is a free comprehensive multimedia curricula for health professionals caring for persons with cancer and their families. The curricula is available as an online Self-Study Section and as a CD-ROM you can order.

  15. Internalization of exogenous human immunodeficiency virus-1 protein, Tat, by KG-1 oligodendroglioma cells followed by stimulation of DNA replication initiated at the JC virus origin.

    PubMed

    Daniel, Dianne C; Kinoshita, Yayoi; Khan, M Aamir; Del Valle, Luis; Khalili, Kamel; Rappaport, Jay; Johnson, Edward M

    2004-12-01

    JC virus (JCV) is the etiological agent of an opportunistic brain infection, progressive multifocal leukoencephalopathy (PML), in AIDS. PML is fatal in approximately 4% of HIV-infected individuals, and although the overall incidence has fallen due to highly aggressive antiretroviral therapy (HAART), this percent has remained steady. It has been shown that the Tat protein of human immunodeficiency virus-1 (HIV-1) interacts in cells with cellular protein Puralpha. This interaction can stimulate transcription of both HIV-1 and JCV genes. HIV-1, however, infects primarily microglia and astrocytes in the brain, whereas JCV infects primarily oligodendrocytes. Although HIV-1 has been shown capable of infecting oligodendrocytes in vitro (Albright et al., 1996), no instance of viral coinfection of such cells with JCV has been reported. Tat is known to be secreted from cells in which it is made. Here we ask whether such exogenous Tat can influence JCV replication in oligodendrocytes. We find that glial cells infected with either HIV-1 or JCV are in proximity at the outer edge of PML lesions. Exogenous Tat is avidly incorporated into cultured KG-1 oligodendroglioma cells over a 72-h period and is colocalized with endogenous Puralpha both nuclear and juxtanuclear. At concentrations in the medium well below the pM range, Tat stimulates several-fold the replication in vivo of DNA initiated at the JCV origin. These results define a pathway by which a protein made by HIV-1 can directly affect the course of infection by another disease-causing virus. PMID:15684713

  16. Anal Human Papillomavirus Genotype Distribution in HIV-Infected Men Who Have Sex with Men by Geographical Origin, Age, and Cytological Status in a Spanish Cohort

    PubMed Central

    Torres, Montserrat; González, Cristina; del Romero, Jorge; Viciana, Pompeyo; Ocampo, Antonio; Rodríguez-Fortúnez, Patricia; Masiá, Mar; Blanco, José Ramón; Portilla, Joaquín; Rodríguez, Carmen; Hernández-Novoa, Beatriz; del Amo, Julia

    2013-01-01

    Knowledge of human papillomavirus (HPV) type distribution in populations at risk for anal cancer is needed. Here, we describe the anal HPV genotype distribution in a large Spanish cohort (Cohort of the Spanish HIV Research Network HPV [CoRIS-HPV]) of HIV-positive men who have sex with men (MSM) according to geographical origin, age, and cytological status. A cross-sectional analysis of baseline data from 1,439 HIV-infected MSM (2007 to 2012) was performed. Anal HPV genotyping was performed using the Linear Array HPV genotyping test. Descriptive analyses of subject characteristics, prevalences, and 95% confidence intervals (CI) were performed. The global prevalences of HPV, high-risk HPV (HR-HPV), and low-risk HPV (LR-HPV) types were 95.8%, 83.0%, and 72.7%, respectively. Among the HR-HPV types, HPV16 was the most common, followed by HPV59, -39, -51, -18, and -52. The prevalence of multiple HR-HPV infections was 58.5%. There were no differences in the crude analyses between Spanish and Latin-American MSM for most HPV types, and a peak in prevalence for most HPV types was seen in patients in their late thirties. Globally and by specific HPV groups, men with abnormal anal cytologies had a higher prevalence of infection than those with normal cytologies. This study has the largest number of HIV-positive MSM with HPV genotype data analyzed according to cytological status as far as we know. The information gained from this study can help with the design of anal cancer prevention strategies in HIV-positive patients. PMID:23966501

  17. Anal human papillomavirus genotype distribution in HIV-infected men who have sex with men by geographical origin, age, and cytological status in a Spanish cohort.

    PubMed

    Torres, Montserrat; González, Cristina; del Romero, Jorge; Viciana, Pompeyo; Ocampo, Antonio; Rodríguez-Fortúnez, Patricia; Masiá, Mar; Blanco, José Ramón; Portilla, Joaquín; Rodríguez, Carmen; Hernández-Novoa, Beatriz; del Amo, Julia; Ortiz, Marta

    2013-11-01

    Knowledge of human papillomavirus (HPV) type distribution in populations at risk for anal cancer is needed. Here, we describe the anal HPV genotype distribution in a large Spanish cohort (Cohort of the Spanish HIV Research Network HPV [CoRIS-HPV]) of HIV-positive men who have sex with men (MSM) according to geographical origin, age, and cytological status. A cross-sectional analysis of baseline data from 1,439 HIV-infected MSM (2007 to 2012) was performed. Anal HPV genotyping was performed using the Linear Array HPV genotyping test. Descriptive analyses of subject characteristics, prevalences, and 95% confidence intervals (CI) were performed. The global prevalences of HPV, high-risk HPV (HR-HPV), and low-risk HPV (LR-HPV) types were 95.8%, 83.0%, and 72.7%, respectively. Among the HR-HPV types, HPV16 was the most common, followed by HPV59, -39, -51, -18, and -52. The prevalence of multiple HR-HPV infections was 58.5%. There were no differences in the crude analyses between Spanish and Latin-American MSM for most HPV types, and a peak in prevalence for most HPV types was seen in patients in their late thirties. Globally and by specific HPV groups, men with abnormal anal cytologies had a higher prevalence of infection than those with normal cytologies. This study has the largest number of HIV-positive MSM with HPV genotype data analyzed according to cytological status as far as we know. The information gained from this study can help with the design of anal cancer prevention strategies in HIV-positive patients. PMID:23966501

  18. Remodeling of the human papillomavirus type 11 replication origin into discrete nucleoprotein particles and looped structures by the E2 protein.

    PubMed

    Sim, Jeonggu; Ozgur, Sezgin; Lin, Biing Yuan; Yu, Jei-Hwa; Broker, Thomas R; Chow, Louise T; Griffith, Jack

    2008-01-25

    The human papillomavirus (HPV) DNA replication origin (ori) shares a common theme with many DNA control elements in having multiple binding sites for one or more proteins spaced over several hundreds of base pairs. The HPV type 11 ori spans 103 bp and contains three palindromic E2 binding sites (E2BS-2, E2BS-3, and E2BS-4) for the dimeric E2 ori binding protein. These sites are separated by 64 and 3 bp. E2BS-1 is located 288 bp upstream of E2BS-2 and is not required for efficient transient or cell-free replication. In this study, electron microscopy was used to visualize complexes of HPV-11 DNA ori bound by purified E2 protein. DNA containing only E2BS-2 showed a single E2 dimer bound. DNA containing E2BS-3 and E2BS-4 showed two side-by-side E2 dimers, while DNA containing E2BS-2, E2BS-3, and E2BS-4 exhibited a large disk/ring-shaped protein particle bound, indicating that the DNA had been remodeled into a discrete complex, likely containing an E2 hexamer. With all four binding sites present, up to 27% of the DNA molecules were arranged into loops by E2, the majority of which spanned E2BS-1 and one of the other three sites. Studies on the dependence of looping on salt, ATP, and DTT using full-length E2 and an E2 protein containing only the carboxyl-terminal DNA binding and protein dimerization domain suggest that looping is dependent on the N-terminal domain and factors that may affect the manner in which E2 scans DNA for binding sites. The role of these structures in the modeling and regulation of the HPV-11 ori is discussed. PMID:18067922

  19. African Origin of Human T-Lymphotropic Virus Type 2 (HTLV-2) Supported by a Potential New HTLV-2d Subtype in Congolese Bambuti Efe Pygmies

    PubMed Central

    Vandamme, Anne-Mieke; Salemi, Marco; Van Brussel, Marianne; Liu, Hsin-Fu; Van Laethem, Kristel; Van Ranst, Marc; Michels, Ludovic; Desmyter, Jan; Goubau, Patrick

    1998-01-01

    We identified a potential new subtype within human T-cell lymphotropic virus type 2 (HTLV-2), HTLV-2d, present in members of an isolated Efe Bambuti Pygmy tribe. Two of 23 Efe Pygmies were HTLV-2 seropositive, with HTLV-2 Western blot and enzyme-linked immunosorbent assay reactivities. From one of them the entire genome of the HTLV-2 strain Efe2 could be amplified and sequenced. In all gene regions analyzed, this strain was the most divergent HTLV-2 strain, differing by 2.4% (tax/rex) to 10.7% (long terminal repeat) from both subtypes HTLV-2a and HTLV-2b, yet major functional elements are conserved. The similarity between the HTLV-2 Efe2 Gag and Env proteins and the corresponding HTLV-2a and -2b proteins is consistent with the observed serological reactivity. In the proximal pX region, one of the two alternative splice acceptor sites is abolished in HTLV-2 Efe2. Another interesting feature of this potential new subtype is that it has a Tax protein of 344 amino acids (aa), which is intermediate in length between the HTLV-2a Tax protein (331 aa) and the HTLV-2b and -2c Tax proteins (356 aa) and similar to the simian T-cell lymphotropic virus type 2 (STLV-2) PP1664 Tax protein. Together these two findings suggest a different phenotype for the HTLV-2 Efe2 strain. Phylogenetic analyses confirmed that the Pygmy Efe2 strain potentially belonged to a new and quite divergent subtype, HTLV-2d. When the STLV-2 bonobo viruses PP1664 and PanP were used as an outgroup, it was clear that the Pygmy HTLV-2 Efe2 strain had the longest independent evolution and that HTLV-2 evolution is consistent with an African origin. PMID:9557723

  20. Expression Pattern of Alternative Splicing Variants of Human Telomerase Reverse Transcriptase (hTERT) in Cancer Cell Lines Was not Associated with the Origin of the Cells

    PubMed Central

    Khosravi- Maharlooei, Mohsen; Jaberipour, Mansooreh; Hosseini Tashnizi, Ahmad; Attar, Armin; Amirmoezi, Fatemeh; Habibagahi, Mojtaba

    2015-01-01

    Telomerase and systems controlling their activity have been of great attention. There are controversies regarding the role of the alternative splicing forms of the human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase. Therefore, the correlation between telomerase enzyme activity, the abundance of alternatively spliced variants of hTERT and doubling time of a series of cancer cell lines originated from hematopoietic, breast, colorectal, neural, ovarian, lung, kidney, bladder, prostate and head and neck cancers were investigated. Expression levels of four different variants of hTERT (the full length, α-deletion, β-deletion and α/β-deletion) were quantitatively measured by real time PCR. Telomerase activity was determined by the telomerase repeat amplification protocol (TRAP) while doubling time of the cells measured by plotting growth curves. Results showed high diversity in the relative proportions of hTERT transcripts while the majority of the cells expressed the full length variant as the main transcript. Telomerase activity could not be detected in all cells. Relative assessment of hTERT expression showed greater expression of the α-deleted variant in the telomerase negative cells (P= 0.04). Those cells possessed the α/β-deleted variant to a smaller extent when compared to the cells with telomerase activity. Greater association between full length spliced variant and β-variant expression was observed in cells presenting telomerase activity (P= 0.0007, r= 0.74). High degrees of variation among the studied cells regarding the pattern of hTERT expression were present. In spite that, the regulatory roles of hTERT on telomerase activity is still a potential to be utilized as targets for cancer therapies. PMID:26261800

  1. Patterns of Ancestral Human Diversity: An Analysis of Alu-Insertion and Restriction-Site Polymorphisms

    PubMed Central

    Watkins, W. S.; Ricker, C. E.; Bamshad, M. J.; Carroll, M. L.; Nguyen, S. V.; Batzer, M. A.; Harpending, H. C.; Rogers, A. R.; Jorde, L. B.

    2001-01-01

    We have analyzed 35 widely distributed, polymorphic Alu loci in 715 individuals from 31 world populations. The average frequency of Alu insertions (the derived state) is lowest in Africa (.42) but is higher and similar in India (.55), Europe (.56), and Asia (.57). A comparison with 30 restriction-site polymorphisms (RSPs) for which the ancestral state has been determined shows that the frequency of derived RSP alleles is also lower in Africa (.35) than it is in Asia (.45) and in Europe (.46). Neighbor-joining networks based on Alu insertions or RSPs are rooted in Africa and show African populations as separate from other populations, with high statistical support. Correlations between genetic distances based on Alu and nuclear RSPs, short tandem-repeat polymorphisms, and mtDNA, in the same individuals, are high and significant. For the 35 loci, Alu gene diversity and the diversity attributable to population subdivision is highest in Africa but is lower and similar in Europe and Asia. The distribution of ancestral alleles is consistent with an origin of early modern human populations in sub-Saharan Africa, the isolation and preservation of ancestral alleles within Africa, and an expansion out of Africa into Eurasia. This expansion is characterized by increasing frequencies of Alu inserts and by derived RSP alleles with reduced genetic diversity in non-African populations. PMID:11179020

  2. Back to the Origin

    PubMed Central

    Evertts, Adam G.

    2012-01-01

    In bacteria, replication is a carefully orchestrated event that unfolds the same way for each bacterium and each cell division. The process of DNA replication in bacteria optimizes cell growth and coordinates high levels of simultaneous replication and transcription. In metazoans, the organization of replication is more enigmatic. The lack of a specific sequence that defines origins of replication has, until recently, severely limited our ability to define the organizing principles of DNA replication. This question is of particular importance as emerging data suggest that replication stress is an important contributor to inherited genetic damage and the genomic instability in tumors. We consider here the replication program in several different organisms including recent genome-wide analyses of replication origins in humans. We review recent studies on the role of cytosine methylation in replication origins, the role of transcriptional looping and gene gating in DNA replication, and the role of chromatin’s 3-dimensional structure in DNA replication. We use these new findings to consider several questions surrounding DNA replication in metazoans: How are origins selected? What is the relationship between replication and transcription? How do checkpoints inhibit origin firing? Why are there early and late firing origins? We then discuss whether oncogenes promote cancer through a role in DNA replication and whether errors in DNA replication are important contributors to the genomic alterations and gene fusion events observed in cancer. We conclude with some important areas for future experimentation. PMID:23634256

  3. Identification of novel vga(A)-carrying plasmids and a Tn5406-like transposon in meticillin-resistant Staphylococcus aureus and Staphylococcus epidermidis of human and animal origin.

    PubMed

    Lozano, Carmen; Aspiroz, Carmen; Rezusta, Antonio; Gómez-Sanz, Elena; Simon, Carmen; Gómez, Paula; Ortega, Carmelo; Revillo, Maria José; Zarazaga, Myriam; Torres, Carmen

    2012-10-01

    Nine staphylococcal strains of human and animal