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1

East African megadroughts between 135 and 75 thousand years ago and bearing on early-modern human origins  

PubMed Central

The environmental backdrop to the evolution and spread of early Homo sapiens in East Africa is known mainly from isolated outcrops and distant marine sediment cores. Here we present results from new scientific drill cores from Lake Malawi, the first long and continuous, high-fidelity records of tropical climate change from the continent itself. Our record shows periods of severe aridity between 135 and 75 thousand years (kyr) ago, when the lake's water volume was reduced by at least 95%. Surprisingly, these intervals of pronounced tropical African aridity in the early late-Pleistocene were much more severe than the Last Glacial Maximum (LGM), the period previously recognized as one of the most arid of the Quaternary. From these cores and from records from Lakes Tanganyika (East Africa) and Bosumtwi (West Africa), we document a major rise in water levels and a shift to more humid conditions over much of tropical Africa after ?70 kyr ago. This transition to wetter, more stable conditions coincides with diminished orbital eccentricity, and a reduction in precession-dominated climatic extremes. The observed climate mode switch to decreased environmental variability is consistent with terrestrial and marine records from in and around tropical Africa, but our records provide evidence for dramatically wetter conditions after 70 kyr ago. Such climate change may have stimulated the expansion and migrations of early modern human populations.

Scholz, Christopher A.; Johnson, Thomas C.; Cohen, Andrew S.; King, John W.; Peck, John A.; Overpeck, Jonathan T.; Talbot, Michael R.; Brown, Erik T.; Kalindekafe, Leonard; Amoako, Philip Y. O.; Lyons, Robert P.; Shanahan, Timothy M.; Castaneda, Isla S.; Heil, Clifford W.; Forman, Steven L.; McHargue, Lanny R.; Beuning, Kristina R.; Gomez, Jeanette; Pierson, James

2007-01-01

2

Early modern human diversity suggests subdivided population structure and a complex out-of-Africa scenario  

Microsoft Academic Search

The interpretation of genetic evidence regarding modern human origins depends, among other things, on assessments of the structure and the variation of ancient populations. Because we lack genetic data from the time when the first anatomically modern humans appeared, between 200,000 and 60,000 years ago, instead we exploit the phenotype of neurocranial geometry to compare the variation in early modern

Philipp Gunz; Fred L. Bookstein; Philipp Mitteroecker; Andrea Stadlmayr; Horst Seidler; Gerhard W. Weber

2009-01-01

3

European early modern humans and the fate of the Neandertals  

PubMed Central

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.

Trinkaus, Erik

2007-01-01

4

European early modern humans and the fate of the Neandertals  

Microsoft Academic Search

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

Erik Trinkaus

2007-01-01

5

Experimental Evidence Concerning Spear Use in Neandertals and Early Modern Humans  

Microsoft Academic Search

Can a bimanual activity such as thrusting a spear during hunting produce bilateral asymmetries in the strength of the upper limbs? This question is important to arguments about the predatory capabilities of Neandertals and early modern humans. To address this question, we determined the magnitude and direction of reaction forces on the upper limbs during thrusting spear use. We collected

Daniel Schmitt; Steven E. Churchill; William L. Hylander

2003-01-01

6

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

Microsoft Academic Search

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

Wesley A. Niewoehner

2001-01-01

7

Early modern humans from the Pe?tera Muierii, Baia de Fier, Romania  

PubMed Central

The early modern human remains from the Pe?tera Muierii, Romania have been directly dated to ?30,000 radiocarbon years before present (?30 ka 14C BP) (?35 ka cal BP) (“calendrical” age; based on CalPal 2005) and augment a small sample of securely dated, European, pre-28 ka 14C BP (?32.5 ka cal BP) modern human remains. The Muierii fossils exhibit a suite of derived modern human features, including reduced maxillae with pronounced canine fossae, a narrow nasal aperture, small superciliary arches, an arched parietal curve, zygomatic arch above the auditory porous, laterally bulbous mastoid processes, narrow mandibular corpus, reduced anterior dentition, ventral-to-bisulcate scapular axillary border, and planoconcave tibial and fibular diaphyseal surfaces. However, these traits co-occur with contextually archaic and/or Neandertal features, including a moderately low frontal arc, a large occipital bun, a high coronoid process and asymmetrical mandibular notch, a more medial mandibular notch crest to condylar position, and a narrow scapular glenoid fossa. As with other European early modern humans, the mosaic of modern human and archaic/Neandertal features, relative to their potential Middle Paleolithic ancestral populations, indicates considerable Neandertal/modern human admixture. Moreover, the narrow scapular glenoid fossa suggests habitual movements at variance with the associated projectile technology. The reproductive and scapulohumeral functional inferences emphasize the subtle natures of behavioral contrasts between Neandertals and these early modern Europeans.

Soficaru, Andrei; Dobos, Adrian; Trinkaus, Erik

2006-01-01

8

The Ob?azowa 1 early modern human pollical phalanx and Late Pleistocene distal thumb proportions.  

PubMed

The human distal thumb phalanx from the earlier Upper Paleolithic of Ob?azowa 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

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

2014-02-01

9

DNA analysis of an early modern human from Tianyuan Cave, China.  

PubMed

Hominins with morphology similar to present-day humans appear in the fossil record across Eurasia between 40,000 and 50,000 y ago. The genetic relationships between these early modern humans and present-day human populations have not been established. We have extracted DNA from a 40,000-y-old anatomically modern human from Tianyuan Cave outside Beijing, China. Using a highly scalable hybridization enrichment strategy, we determined the DNA sequences of the mitochondrial genome, the entire nonrepetitive portion of chromosome 21 (?30 Mbp), and over 3,000 polymorphic sites across the nuclear genome of this individual. The nuclear DNA sequences determined from this early modern human reveal that the Tianyuan individual derived from a population that was ancestral to many present-day Asians and Native Americans but postdated the divergence of Asians from Europeans. They also show that this individual carried proportions of DNA variants derived from archaic humans similar to present-day people in mainland Asia. PMID:23341637

Fu, Qiaomei; Meyer, Matthias; Gao, Xing; Stenzel, Udo; Burbano, Hernán A; Kelso, Janet; Pääbo, Svante

2013-02-01

10

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

PubMed Central

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.

Richards, Michael P.; Trinkaus, Erik

2009-01-01

11

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

PubMed

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

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

2014-04-01

12

Desert speleothems reveal climatic window for African exodus of early modern humans  

NASA Astrophysics Data System (ADS)

One of the first movements of early modern humans out of Africa occurred 130-100 thousand years ago (ka), when they migrated northward to the Levant region. The climatic conditions that accompanied this migration are still under debate. Using high-precision multicollector-inductively coupled plasma-mass spectrometry (MC-ICP-MS) U-Th methods, we dated carbonate cave deposits (speleothems) from the central and southern Negev Desert of Israel, located at the northeastern margin of the Saharan-Arabian Desert. Speleothems grow only when rainwater enters the unsaturated zone, and this study reveals that a major cluster of wet episodes (the last recorded in the area) occurred between 140 and 110 ka. This episodic wet period coincided with increased monsoonal precipitation in the southern parts of the Saharan-Arabian Desert. The disappearance at this time of the desert barrier between central Africa and the Levant, and particularly in the Sinai-Negev land bridge between Africa and Asia, would have created a climatic “window” for early modern human dispersion to the Levant.

Vaks, Anton; Bar-Matthews, Miryam; Ayalon, Avner; Matthews, Alan; Halicz, Ludwik; Frumkin, Amos

2007-09-01

13

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

PubMed

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

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; Boric, Dusan; 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

2012-08-21

14

Late Neandertals and Early Modern Humans in Europe, Population Dynamics and Paleobiology  

Microsoft Academic Search

\\u000a On the sesquicentennial of the discovery at the Kleine Feldhofer Grotte, it is appropriate to reassess the nature of the biological\\u000a transition between late Neandertals and the earliest modern humans in Europe. An assessment of the latter sample shows a predominantly\\u000a modern human morphological pattern, but the persistent and varied presence of distinctive Neandertal features and\\/or archaic\\u000a traits lost or

Erik Trinkaus

15

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)

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.

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

2008-12-01

16

Early modern experimentation on live animals.  

PubMed

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

Bertoloni Meli, Domenico

2013-01-01

17

A critique of the evidence for scavenging by Neandertals and early modern humans: new data from Kobeh Cave (Zagros Mountains, Iran) and Die Kelders Cave 1 Layer 10 (South Africa)  

Microsoft Academic Search

The primary mode of faunal exploitation by Neandertals and early modern humans remains a debated topic. Binford (1981, 1984, 1985, 1988) has argued for an obligate scavenging mode, Stiner (1991a, 1991b, 1991c, 1993, 1994) for a more opportunistic scavenging mode, while other researchers (Chase, 1986, 1988, 1989; Klein, 1989, 1994, 1995; Klein & Cruz-Uribe, 1996) deny the importance of scavenging

Curtis W. Marean

1998-01-01

18

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

PubMed Central

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.

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

2011-01-01

19

The Bab al Mandab vs the Nile-Levant: An Appraisal of the Two Dispersal Routes for Early Modern Humans Out of Africa  

Microsoft Academic Search

There is a growing convergence of paleontological, archaeological and genetic evidence for the African origin of modern humans and their successive dispersals. However, there is disagreement about the route or routes taken by early humans during their migration out of Africa. This article examines the Middle Paleolithic\\/Middle Stone Age archaeological evidence from the Horn of Africa, the Nile Valley\\/eastern Sahara,

Amanuel Beyin

2006-01-01

20

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

Microsoft Academic Search

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

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

2008-01-01

21

Non-metric variation in recent humans as a model for understanding Neanderthal-early modern human differences: just how “unique” are Neanderthal unique traits?  

Microsoft Academic Search

Using living humans as an extant referent, this paper examines the probability that the frequency differences in Neanderthal\\u000a “unique” non-metric traits observed between Neanderthals and Upper Paleolithic modern humans could be sampled from two major\\u000a populations of the same species. Neanderthal-like features occur in very low frequencies in living humans, if present at all.\\u000a Rather, other features distinguish major human

J. C. M. AHERN

22

Bolatu's pharmacy theriac in early modern China.  

PubMed

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

Nappi, Carla

2009-01-01

23

Early Modern India and World History.  

ERIC Educational Resources Information Center

Characterizes the early modern period in world history (roughly 1500-1800) as one marked by worldwide processes of change unprecedented in scope and intensity. Argues that the society of the Indian subcontinent shared directly in the massive processes of change that influenced societies throughout the world. (MJP)

Richards, John F.

1997-01-01

24

The Medieval and Early Modern Data Bank.  

ERIC Educational Resources Information Center

Illustrates the use of computer data banks in history by examining the Medieval and Early Modern Data Bank (MEMDB) located at Rutgers University. States the database contains an expanding collection of historical monetary and price/wage data. Includes instructions, examples of search strategies, and an annotated bibliography. (CFR)

Touwen, L. Jeroen

1992-01-01

25

Wallerstein, World Systems Analysis, and Early Modern European History.  

ERIC Educational Resources Information Center

Surveys evaluations of Immanuel Wallerstein's "The Modern World-System" by specialists in early modern history and examines Wallerstein's influence on early modern historiography. Concludes by considering some attempts to synthesize world-systems analysis with other approaches. (LS)

DuPlessis, Robert S.

1988-01-01

26

Attending to Early Modern Women: Gender, Culture, and Change  

NSDL National Science Digital Library

This Web site provides annotated links to high quality academic resources useful for the study of women in early modern Europe and the Americas. Specific focus is on periods between the sixteenth and eighteenth centuries; however, links also include some medieval and nineteenth century resources. Selected by members of the Arts and Humanities Team of the University of Maryland Libraries, materials range from bibliographic databases to full-text resources, images, and sound recordings. Viewers may search the database by keyword or browse by title, subject, reference type, time period, language, or geographic area. Although most of the resource links are free, some require a license for access.

2001-01-01

27

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

PubMed

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

Keiser, George R

2003-07-01

28

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

ERIC Educational Resources Information Center

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…

Naylor, Amanda

2013-01-01

29

Cioclovina (Romania): affinities of an early modern European  

Microsoft Academic Search

The current modern human origins debate centers on the possibility and degree of admixture between indigenous archaic humans and modern human populations migrating out of Africa into Europe and Asia in the Late Pleistocene. Evidence for such admixture must be sought in the earliest fossil record of modern humans outside Africa, as it is those populations that would have encountered,

Katerina Harvati; Philipp Gunz; Dan Grigorescu

2007-01-01

30

Becoming Human: Paleoanthropology, Evolution, and Human Origins  

NSDL National Science Digital Library

A project involving Arizona State University's Institute for Human Origins (founded and directed by Donald C. Johanson, best-known for his discovery of "Lucy"), documentary filmmaker Lenora C. Johanson, and Terra Incognita, this site is designed to teach a general audience about human evolution and the search for early hominid life in the field. The key feature of the site is an extensive (and very professional) flash-driven, online documentary which includes a number of pop-up sub-exhibits that provide additional information and resources on various topics. Other sections of the site include News & Views, which offers recent paleo news stories and expert views, and Resources, which includes a glossary, related sites, and media references. A Learning Center with activities and lesson plans is scheduled to be added this summer. This site, probably the best online documentary seen by this reviewer, should appeal to anyone with an interest in human origins and is highly recommended.

2001-01-01

31

Food for healing: Convalescent cookery in the early modern era.  

PubMed

Despite major theoretical shifts in early modern nutritional theory, from humoralism to chemical and mechanical systems, the form and structure of convalescent cookery remained remarkably constant throughout the era and to a large extent even down to the present. In medical texts, cookbooks and in the popular imagination convalescent food generally mirrored food for infants, being soft and bland, based on dairy and grains, as well as foods considered highly nutritious yet easy to digest like concentrated broths. This article traces the development of ideas about convalescent food and how little they change over time. PMID:22520181

Albala, Ken

2012-06-01

32

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

PubMed

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

Yale, Elizabeth

2011-06-01

33

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

PubMed

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, Kor?ula, 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 DrŽi?, 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 DrŽi? (1508-1567) as the exemplars of English and Croatian Renaissance literature. PMID:23094840

Atalic, Bruno

2012-01-01

34

Metaphors and images of cancer in early modern Europe.  

PubMed

Drawing on learned medical writing about cancer and on nonmedical texts that used cancer as a metaphor for hateful cultural, social, religious, or political phenomena that warranted drastic measures, this article traces the metaphors and images that framed the perception and experience of cancer in the early modern period. It finds that cancer was closely associated with notions of impurity and a visible destruction of the body's surface and was diagnosed primarily in women, as breast and uterine cancer. Putrid, corrosive cancerous humor was thought not only to accumulate and eat its way into the surrounding flesh but also to spread, like the seeds of a plant, "infecting" the whole body. This infectious quality, the putrid secretions, and the often horrendous smell emanating from cancer victims raised fears, in turn, of contagion and were taken to justify a separation of cancer patients from the rest of society. PMID:24769802

Stolberg, Michael

2014-01-01

35

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

ERIC Educational Resources Information Center

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…

Damsen, Silver

2009-01-01

36

Pe?tera cu Oase 2 and the cranial morphology of early modern Europeans  

PubMed Central

Between 2003 and 2005, the Pe?tera 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.

Rougier, Helene; Milota, Stefan; Rodrigo, Ricardo; Gherase, Mircea; Sarcina, Laurentiu; Moldovan, Oana; Zilhao, Joao; Constantin, Silviu; Franciscus, Robert G.; Zollikofer, Christoph P. E.; Ponce de Leon, Marcia; Trinkaus, Erik

2007-01-01

37

Modern human origins: progress and prospects.  

PubMed Central

The question of the mode of origin of modern humans (Homo sapiens) has dominated palaeoanthropological debate over the last decade. This review discusses the main models proposed to explain modern human origins, and examines relevant fossil evidence from Eurasia, Africa and Australasia. Archaeological and genetic data are also discussed, as well as problems with the concept of 'modernity' itself. It is concluded that a recent African origin can be supported for H. sapiens, morphologically, behaviourally and genetically, but that more evidence will be needed, both from Africa and elsewhere, before an absolute African origin for our species and its behavioural characteristics can be established and explained.

Stringer, Chris

2002-01-01

38

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

PubMed

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 Medicin

Boehm, Laetitia

2008-01-01

39

An anthropometric history of early-modern France  

Microsoft Academic Search

The height of the French male population of the Ancien R gime is estimated, on the basis of military records, to have been about 162 cm in the seventeenth century. This extremely short stature implies that the crisis of the 17th century had an immense impact on the human organism itself. The improvement in climatic conditions at the turn of

John Komlos

2003-01-01

40

An anthropometric history of early-modern France  

Microsoft Academic Search

The height of the French male population of the Ancien Régime is estimated, on the basis of military records, to have been about 162 cm in the seventeenth century. This extremely short stature implies that 'the crisis of the 17th century' had an immense impact on the human organism itself. The improvement in climatic conditions at the turn of the

JOHN KOMLOS; MICHEL HAU; NICOLAS BOURGUINAT

2003-01-01

41

Identifying the seasonal origins of human campylobacteriosis  

PubMed Central

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.

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

42

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

ERIC Educational Resources Information Center

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…

Cady, Christina J.

2010-01-01

43

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

ERIC Educational Resources Information Center

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…

Rutz, Andreas

2012-01-01

44

Repression and Change in the Sexual Life of Young People in Medieval and Early Modern Times  

ERIC Educational Resources Information Center

French demographic historians have not taken sufficient notice of the hypothesis that sexual repression intensified throughout the early modern period and they have too readily assumed that it was demolished by their statistical data. It is therefore useful to explain what makes the hypothesis plausible. (Author)

Flandrin, J. L.

1977-01-01

45

'Abhorreas pinguedinem': Fat and obesity in early modern medicine (c. 1500-1750).  

PubMed

Contrary to a widely held belief, the medicalization of obesity is not a recent development. Obesity was extensively discussed in leading early modern medical textbooks, as well as in dozens of seventeenth- and eighteenth-century dissertations. Drawing upon ancient and medieval writings, these works discussed the negative impact of obesity upon health and linked it with premature death. Obesity was particularly associated with apoplexy, paralysis, asthma and putrid fevers, and a range of therapeutic options was proposed. This paper offers a first survey of the medical understanding of the causes, effects and treatment of obesity in the early modern period. It examines the driving forces behind the physicians' interest and traces the apparently rather limited response to their claims among the general public. Comparing early modern accounts of obesity with the views and stereotypes prevailing today, it notes the impact of changing medical, moral and aesthetic considerations and identifies, among other things, a shift in the early modern period from concepts of pathological compression to images of the obese body as lax and boundless. PMID:22520186

Stolberg, Michael

2012-06-01

46

States, Republics, and Empires: The American Founding in Early Modern Perspective.  

ERIC Educational Resources Information Center

Views the founding of the United States by analyzing key terms in its language in contexts provided by the history of early modern political discourse. Focuses on the transformation of the words "federative" and "federal." Concludes by examining the presidency as the monarchical component of an imperial republic. (Author/LS)

Pocock, J. G. A.

1987-01-01

47

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

PubMed

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

Jütte, Daniel

2012-12-01

48

Passions, acting and face in early modern characters: an alternative view on the avatar.  

PubMed

While the emergence of the Internet and mobile telephone has allegedly changed our concept of self and emotions, the fundamental idea of a character seems to remain unchanged since literary characters came into 'stock' in the early modern imagination. Focusing on the early modern literary sphere, this commentary examines how the contemporary avatar stems from the early modern concept of character. Taking some examples from the writings of Thomas Overbury, Ben Jonson and Shakespeare amongst others, it investigates the concept of character and the self in the literary, legal, and medical discourses. It then analyses the practical application of characters in the theatrical spheres. Following these findings, the study examines the dramatic texts and argues the importance of face in the character creation and apprehension, finding a curious correlation to the indispensable use of avatars on the Internet. The research thus indicates that the concept of characters is not only fundamental to the contemporary virtual life but also equally vital to the early modern literary experience, offering an alternative view to Simon Evans's paper that examines the continuities of selves in the virtual and the physical worlds, as well as in the present and the past. PMID:23054608

Shimizu, Akihiko

2012-12-01

49

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

ERIC Educational Resources Information Center

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…

Cormack, Lesley B.

2006-01-01

50

"False Fonde Bookes, Ballades and Rimes": An Aspect of Informal Education in Early Modern England.  

ERIC Educational Resources Information Center

Explains the negative response of those in authority to early modern English literature which informally educated the population through "false fonde bookes, ballades, and rimes." This negative response, based on both moral and political grounds, came from clerics who saw such books as detrimental to the social structure of society. (BSR)

Charlton, Kenneth

1987-01-01

51

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

ERIC Educational Resources Information Center

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…

Chamberland, Celeste

2013-01-01

52

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

ERIC Educational Resources Information Center

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…

Bruter, Annie

2012-01-01

53

Between Charity and Education: Orphans and Orphanages in Early Modern Times  

ERIC Educational Resources Information Center

In early modern times orphans have been children who could not expect sufficient support from their family because of lack of at least one parent, in most cases the father. This article will clarify of whom we are talking if we talk about orphans and what have been the conditions of living in a society which was organised by a high variety of…

Jacobi, Juliane

2009-01-01

54

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

ERIC Educational Resources Information Center

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…

Maffioli, Cesare S.

2013-01-01

55

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

PubMed

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

Kahn, Didier

2011-03-01

56

Assembly of the human origin recognition complex.  

PubMed

The six-subunit origin recognition complex (ORC) was originally identified in the yeast Saccharomyces cerevisiae. Yeast ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors, such as Cdc6 and the Mcm proteins. Human homologues of all six ORC subunits have been identified by sequence similarity to their yeast counterparts, but little is known about the biochemical characteristics of human ORC (HsORC). We have extracted HsORC from HeLa cell chromatin and probed its subunit composition using specific antibodies. The endogenous HsORC, identified in these experiments, contained homologues of Orc1-Orc5 but lacked a putative homologue of Orc6. By expressing HsORC subunits in insect cells using the baculovirus system, we were able to identify a complex containing all six subunits. To explore the subunit-subunit interactions that are required for the assembly of HsORC, we carried out extensive co-immunoprecipitation experiments with recombinant ORC subunits expressed in different combinations. These studies revealed the following binary interactions: HsOrc2-HsOrc3, HsOrc2-HsOrc4, HsOrc3-HsOrc4, HsOrc2-HsOrc6, and HsOrc3-HsOrc6. HsOrc5 did not form stable binary complexes with any other HsORC subunit but interacted with sub-complexes containing any two of subunits HsOrc2, HsOrc3, or HsOrc4. Complex formation by HsOrc1 required the presence of HsOrc2, HsOrc3, HsOrc4, and HsOrc5 subunits. These results suggest that the subunits HsOrc2, HsOrc3, and HsOrc4 form a core upon which the ordered assembly of HsOrc5 and HsOrc1 takes place. The characterization of HsORC should facilitate the identification of human origins of DNA replication. PMID:11323433

Vashee, S; Simancek, P; Challberg, M D; Kelly, T J

2001-07-13

57

Demonic possession and mental disorder in medieval and early modern Europe.  

PubMed

Western European belief in demonic possession as a cause of mental disorder has been traced through the medieval and early modern periods. Generally it appears that the range of disorders attributed to demonic possession has gradually narrowed. In any period, however, there seem to have been marked individual and cultural differences in outlook; some of these differences are still evident today in the survival of belief in demonic possession in pentecostal sects. PMID:3554292

Kemp, S; Williams, K

1987-02-01

58

The 'spiteful' origins of human cooperation.  

PubMed

We analyse generosity, second-party ('spiteful') punishment (2PP), and third-party ('altruistic') punishment (3PP) in a cross-cultural experimental economics project. We show that smaller societies are less generous in the Dictator Game but no less prone to 2PP in the Ultimatum Game. We might assume people everywhere would be more willing to punish someone who hurt them directly (2PP) than someone who hurt an anonymous third person (3PP). While this is true of small societies, people in large societies are actually more likely to engage in 3PP than 2PP. Strong reciprocity, including generous offers and 3PP, exists mostly in large, complex societies that face numerous challenging collective action problems. We argue that 'spiteful' 2PP, motivated by the basic emotion of anger, is more universal than 3PP and sufficient to explain the origins of human cooperation. PMID:21159680

Marlowe, Frank W; Berbesque, J Colette; Barrett, Clark; Bolyanatz, Alexander; Gurven, Michael; Tracer, David

2011-07-22

59

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

PubMed Central

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.

Leong, Elaine

2013-01-01

60

[Genetics and the origin of human races].  

PubMed

In the last decades, the concept of human races was considered scientifically unfounded as it was not confirmed by genetic evidence. None of the racial classifications, which strongly differ in the number of races and their composition, reflects actual genetic similarity and genealogy of human populations inferred from variability of classical markers and DNA regions. Moreover, intercontinental ("interracial") variability was shown to be far lower than that within populations: the former constitutes 7 to 10% and the latter, about 85% of the total genetic variation. It is believed that the low level of differentiation of regional population groups contradicts their race status and suggests a recent origin of humans from one ancestral population. The results of studies of various genetic systems are in agreement with last conclusion rejecting the hypothesis of regional continuity. According to this hypothesis, the populations of continents regarded as large races have developed during long evolution from local types of archaic humans, in particular, Neanderthals. Phenotypic similarity of different, sometimes unrelated, populations united into one "race" is explained by strong selection since race-diagnostic traits characterize body surface and thus are directly subjected to the influence of environmental (primarily climatic) factors. It has been recently established that variability of the most important of these traits, body and hair pigmentation, is largely controlled by one locus (MC1R), which accounts for its high evolutionary lability. Other traits used for race identification are also likely to be labile and controlled by major genes. However, the fact that the currently existing race classifications are groundless does not mean that such classifications are impossible in principle. Commonly used argumentation (races do not exist because populations are not genetically separated) does not hold water. A polytypic species is characterized by genetic continuity of allopatric populations rather than the presence of narrow genetic boundaries between them. Borderlines between races are usually conventional and arbitrary. As to intergroup variation in humans, it is indeed low but comparable with that in some other species. There are no obstacles to the development of genetic systematics of human races. PMID:11642102

Tetushkin, E Ia

2001-08-01

61

The origin recognition complex in human diseases.  

PubMed

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

Shen, Zhen

2013-01-01

62

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

PubMed

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

Roos, Anna Marie

2008-12-01

63

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

PubMed

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

Kraye, Jill

2012-01-01

64

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

PubMed

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

Karababa, Eminegül

2012-01-01

65

Genetic and Fossil Evidence for the Origin of Modern Humans.  

ERIC Educational Resources Information Center

Discusses how genetic data on present human population relationships and data from the Pleistocene fossil hominid record are being used to compare two contrasting models for the origin of modern humans. (TW)

Stringer, C. B.; Andrews, P.

1988-01-01

66

Origins of Modern Humans: Multiregional or Out of Africa  

NSDL National Science Digital Library

The issue-focused, peer-reviewed article presents the two theories about the origin of modern humans: 1) they arose in one place -- Africa and and 2) pre-modern humans migrated from Africa to become modern humans in other parts of the world. Most evidence points to the first theory because: fossils of modern-like humans are found in Africa, stone tools and other artifacts support African origin, and DNA studies suggest a founding population in Africa.

Donald Johanson (Arizona State University;)

2001-05-01

67

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

PubMed

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

Freller, T

1997-01-01

68

Origin and diversity of human retroviruses.  

PubMed

Simian immunodeficiency viruses, simian T?cell lymphotropic viruses, and simian foamy viruses from nonhuman primates have crossed the species barrier to humans at several time points, leading to the HIV and human T lymphotropic virus epidemic and to sporadic cases of human infections with simian foamy viruses, respectively. Efficient infection and spread in humans differs between simian foamy virus, simian lymphotropic virus, and simian immunodeficiency virus, 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 only spread to some extent in West Africa, and similarly as for HIV?1, the nine HIV?2 groups have also a different epidemic history. Four types of human T lymphotropic virus, type 1 to 4, have been described in humans and for three of them simian counterparts (simian T lymphotropic virus?1, ?2, ?3) have been identified in multiple nonhuman primate species. The majority of human infections are with human T lymphotropic virus?1, which is present throughout the world as clusters of high endemicity. Humans are susceptible to a wide variety of simian foamy viruses and seem to acquire these viruses more readily than simian immunodeficiency viruses or simian T lymphotropic viruses, but neither signs of disease in humans nor human?to?human transmission of simian foamy virus have 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 human T lymphotropic virus?1 and ?3 variants, as well as simian foamy virus infections in humans in Central Africa, show that our knowledge of genetic diversity and cross?species transmissions of simian retroviruses is still incomplete. PMID:24584106

Peeters, Martine; D'Arc, Mirela; Delaporte, Eric

2014-01-01

69

On the origin of modern humans in China  

Microsoft Academic Search

The Multiregional Evolution Hypothesis (MEH) and the Recent Out of Africa Hypothesis (ROAH) are two main hypotheses bearing on the origin of modern humans. In China, there are many common morphological features among Pleistocene human fossil skulls. These features and the morphological mosaic between Homo sapiens erectus and Homo sapiens sapiens of China indicate the continuity of human evolution in

Xinzhi Wu

2004-01-01

70

Making expert knowledge through the image: connections between antiquarian and early modern scientific illustration.  

PubMed

This essay examines drawings of antiquities in the context of the history of early modern scientific illustration. The role of illustrations in the establishment of archaeology as a discipline is assessed, and the emergence of a graphic style for representing artifacts is shown to be closely connected to the development of scientific illustration in the seventeenth and early eighteenth centuries. The essay argues that the production of conventionalized drawings of antiquities during this period represents a fundamental shift in the approach to ancient material culture, signifying the recognition of objects as evidence. As has been demonstrated in other scientific fields, the creation of a visual system for recording objects was central to the acceptance of artifacts as "data" that could be organized into groups, classified as types, and analyzed to gain knowledge of the past. PMID:24855872

Moser, Stephanie

2014-03-01

71

Marital violence in a martial town: husbands and wives in early modern Portsmouth, 1653-1781.  

PubMed

Sessions papers from early modern Portsmouth survive from 1653 on and are nearly continuous for eighty-five years, that is, from 1696 to 1781. They include 356 cases of wife beating in addition to 7,658 other assaults; as such, the town's records allow for a comparison of the violent behavior of individual wife beaters both inside and outside of their marriages. These comparisons suggest that assaults on wives were more severe than assaults on strangers and acquaintances: not only were many wives assaulted on several occasions before lodging a complaint, the attacks themselves often resulted in greater injury, reflecting (1) a greater tendency to use potentially lethal weapons and (2) a differential in strength between most husbands and wives. The motives of individual wife beaters are less clear; what can be said with certainty is that wife beatings, like assaults in general, tended to rise whenever soldiers were demobilized and men were either unemployed or underemployed. PMID:12751490

Warner, Jessica; Lunny, Allyson

2003-04-01

72

The English Galileo: Thomas Harriot and the Force of Shared Knowledge in Early Modern Mechanics  

NASA Astrophysics Data System (ADS)

I discuss the work of the English mathematician and philosopher Thomas Harriot (1560 1621), analyzing especially his work on projectile motion, and comparing it to that of his contemporary Galileo Galilei (1564 1642). I argue that although their work on projectile motion was carried out independently and displays both similarities and differences, it shows that they focused on common challenging objects of study that embodied what I term “points of contact” between preclassical and classical mechanics. I also argue that their shared knowledge defined the space of possible solutions to the problem of projectile motion, although the inferential pathways they followed through their shared knowledge proceeded in exactly opposite directions. I conclude that their work suggests that the lines of development in early modern mechanics converged in such a way that the long-term development of science was largely unaffected by the peculiarities in an individual scientist’s work.

Schemmel, Matthias

2006-12-01

73

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

PubMed Central

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.

McHugh, Tim

2012-01-01

74

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

PubMed

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

Chang, Ku-ming

2011-06-01

75

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

PubMed

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

Seitz, Jonathan

2009-01-01

76

On the origin of the human treponematoses  

PubMed Central

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.

Hackett, C. J.

1963-01-01

77

Understanding Human Trafficking Origin: A Cross-Country Empirical Analysis  

Microsoft Academic Search

Feminist work on global human trafficking has highlighted the conceptual difficulty of differentiating between trafficking and migration. This contribution uses a cross-country United Nations Office on Crime and Drugs dataset on human trafficking from 2006 to empirically evaluate the socioeconomic characteristics of high-trafficking origin countries and compare them with patterns that have emerged in the literature on migration. In particular,

Smriti Rao; Christina Presenti

2012-01-01

78

Origins of the Human Genome Project  

SciTech Connect

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.

Cook-Deegan, Robert

1993-07-01

79

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

PubMed

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

Kahn, Didier

2010-11-01

80

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

PubMed

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

Atalic, Bruno

2012-09-01

81

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

PubMed

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

Crowther, Kathleen M; Barker, Peter

2013-09-01

82

The early modern kidney--nephrology in and about the nineteenth century. Part 1.  

PubMed

The 19th century was a period of momentous scientific discoveries, technological achievements, and societal changes. A beneficiary of these revolutionary upheavals was medical empiricism that supplanted the rationalism of the past giving rise to early modern scientific medicine. Continued reliance on sensory data now magnified by technical advances generated new medical information that could be quantified with increasing precision, verified by repeated experimentation, and validated by statistical analysis. The institutionalization and integration of these methodologies into medical education were a defining step that assured their progress and perpetuation. Major advances were made in the nosography of diseases of the kidney, notably that of the diagnosis of progressive kidney disease from the presence of albuminuria by Richard Bright (1789-1858); and of renal structure and function, notably the demonstration of the continuity of the glomerular capsule with the tubular basement membrane by William Bowman (1816-1892), and the arguments for hemodynamic physical forces mediated glomerular filtration by Carl Ludwig (1816-1895) and for active tubular transport by Rudolf Heidenhain (1834-1897). Improvements in microscopy and tissue processing were instrumental in describing the cellular ultrastructure of the glomerulus and tubular segments, but their integrated function remained to be elucidated. The kidney continued to be considered a tubular secretory organ and its pathology attributed to injury of the interstitium (interstitial nephritis) or tubules (parenchymatous nephritis). PMID:23278189

Eknoyan, Garabed

2013-01-01

83

Trapping DNA Replication Origins from the Human Genome  

PubMed Central

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.

Eki, Toshihiko; Murakami, Yasufumi; Hanaoka, Fumio

2013-01-01

84

A human DNA replication origin: localization and transcriptional characterization  

Microsoft Academic Search

A single-copy 13.7 kb human DNA region (L30E) located on Ch. 19 p13.3 contains an origin of DNA replication in myeloid HL-60\\u000a cells. The origin was localized, by means of quantitative PCR within approximately 3000 bp, in a highly transcribed region\\u000a containing at least two closely spaced genes with the same polarity of transcription, one encoding lamin B2 and the

Giuseppe Biamonti; Giovanni Perini I; Florian Weighardt; Silvano Riva; Mauro Giacca; Paolo Norio; Lorena Zentilin; Silvia Diviacco; Daniela Dimitrova; Arturo Falaschi

1992-01-01

85

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

PubMed

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

Hiruta, Genshiro

2003-01-01

86

The origin and distribution of human lice in the world.  

PubMed

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

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

2014-04-01

87

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

PubMed

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

Brock, W H

2011-11-01

88

Body proportions in Late Pleistocene Europe and modern human origins  

Microsoft Academic Search

Body proportions covary with climate, apparently as the result of climatic selection. Ontogenetic 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

Trenton W. Holliday

1997-01-01

89

'Very Sore Nights and Days': The Child's Experience of Illness in Early Modern England, c.1580-1720  

PubMed Central

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.

NEWTON, HANNAH

2011-01-01

90

Functional interactions of DNA topoisomerases with a human replication origin  

PubMed Central

The human DNA replication origin, located in the lamin B2 gene, interacts with the DNA topoisomerases I and II in a cell cycle-modulated manner. The topoisomerases interact in vivo and in vitro with precise bonds ahead of the start sites of bidirectional replication, within the pre-replicative complex region; topoisomerase I is bound in M, early G1 and G1/S border and topoisomerase II in M and the middle of G1. The Orc2 protein competes for the same sites of the origin bound by either topoisomerase in different moments of the cell cycle; furthermore, it interacts on the DNA with topoisomerase II during the assembly of the pre-replicative complex and with DNA-bound topoisomerase I at the G1/S border. Inhibition of topoisomerase I activity abolishes origin firing. Thus, the two topoisomerases are closely associated with the replicative complexes, and DNA topology plays an essential functional role in origin activation.

Abdurashidova, Gulnara; Radulescu, Sorina; Sandoval, Oscar; Zahariev, Sotir; Danailov, Miltcho B; Demidovich, Alexander; Santamaria, Laura; Biamonti, Giuseppe; Riva, Silvano; Falaschi, Arturo

2007-01-01

91

African origin of human-specific polymorphic Alu insertions  

SciTech Connect

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.

Batzer, M.A.; Alegria-Hartman, M. (Lawrence Livermore National Lab., CA (United States)); Stoneking, M. (Pennsylvania State Univ., University Park, PA (United States)); Bazan, H.; Kass, D.H.; Shaikh, T.H.; Scheer, W.D. (Louisiana State Univ. Medical Center, New Orleans, LA (United States)); Novick, G.E.; Herrera, R.J. (Florida International Univ., Miami, FL (United States)); Ioannou, P.A. (Cyprus Institute of Neurology and Genetics, Nicosia (Cyprus)) (and others)

1994-12-06

92

Subcortical origins of human and monkey neocortical interneurons.  

PubMed

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

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

93

University of Southampton: Centre for the Archaeology of Human Origins  

NSDL National Science Digital Library

Hosted by the University of Southampton, this website presents the Centre for the Archaeology of Human Origins (CAHO). The CAHO website contains information about research projects, publications, and staff. The Research section links to basic information about research projects in the UK, Africa, and Europe. Publication lists, background information, and contacts are provided for CAHO academic staff and research students. The site also contains sections for News & Events, and related Links.

94

Timing the origin of human malarias: the lemur puzzle  

PubMed Central

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.

2011-01-01

95

Origin of the human malaria parasite Plasmodium falciparum in gorillas  

PubMed Central

Plasmodium falciparum is the most prevalent and lethal of the malaria parasites infecting humans, yet the origin and evolutionary history of this important pathogen remain controversial. Here, we developed a novel polymerase chain reaction based single genome amplification strategy to identify and characterize Plasmodium spp. DNA sequences in fecal samples of wild-living apes. Among nearly 3,000 specimens collected from field sites throughout central Africa, we found Plasmodium infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus). Ape plasmodial infections were highly prevalent, widely distributed, and almost always comprised of mixed parasite species. Analysis of more than 1,100 mitochondrial, apicoplast and nuclear gene sequences from chimpanzees and gorillas revealed that 99% grouped within one of six host-specific lineages representing distinct Plasmodium species within the subgenus Laverania. One of these from western gorillas was comprised of parasites that were nearly identical to P. falciparum. In phylogenetic analyses of full-length mitochondrial sequences, human P. falciparum formed a monophyletic lineage within the gorilla parasite radiation. These findings indicate that P. falciparum is of gorilla and not of chimpanzee, bonobo or ancient human origin.

Liu, Weimin; Li, Yingying; Learn, Gerald H.; Rudicell, Rebecca S.; Robertson, Joel D.; Keele, Brandon F.; Ndjango, Jean-Bosco N.; Sanz, Crickette M.; Morgan, David B.; Locatelli, Sabrina; Gonder, Mary K.; Kranzusch, Philip J.; Walsh, Peter D.; Delaporte, Eric; Mpoudi-Ngole, Eitel; Georgiev, Alexander V.; Muller, Martin N.; Shaw, George M.; Peeters, Martine; Sharp, Paul M.; Rayner, Julian C.; Hahn, Beatrice H.

2010-01-01

96

Modern human origins: continuity, replacement, and masticatory robusticity in Australasia.  

PubMed

Morphological evidence for a Multiregional (MR) model of human origins is suggested by a series of "linking traits" seen in the crania of late Javanese Homo erectus from Ngandong and anatomically modern Australian crania. A few studies that consider the genetic, structural, or functional aspects of these regional traits suggest their appearance is heavily influenced not by shared phylogeny but by a common "strong" masticatory pattern. Using dental occlusal areas, external mandibular metrics, internal biomechanical properties of the mandibular corpus measured from CT scans, and nonmetric traits associated with the attachment of masticatory muscles, we test the hypothesis that Australians exhibit evidence of a "strong" masticatory pattern. We use a mixed-sex comparative human sample (n = 415) that includes precontact Alaskans from Point Hope and the Aleutian Islands, Californians, Peruvians, an urban forensic sample, and the late Pleistocene Afalou-Taforalt sample. In comparison with recent humans known to exhibit such patterns, Australian mandibles show none of the expected changes related to producing and dissipating heavy occlusal loads. This is true regardless of whether external or internal mandibular dimensions are considered, albeit Australians show large occlusal areas and relatively large section modulus indices. Thus, a prime functional argument proposed for the origin of some Australian regional features is not supported by these data. PMID:20934739

Antón, Susan C; Carter-Menn, Hannah; DeLeon, Valerie B

2011-01-01

97

Human Salmonella clinical isolates distinct from those of animal origin.  

PubMed

The global trend toward intensive livestock production has led to significant public health risks and industry-associated losses due to an increased incidence of disease and contamination of livestock-derived food products. A potential factor contributing to these health concerns is the prospect that selective pressure within a particular host may give rise to bacterial strain variants that exhibit enhanced fitness in the present host relative to that in the parental host from which the strain was derived. Here, we assessed 184 Salmonella enterica human and animal clinical isolates for their virulence capacities in mice and for the presence of the Salmonella virulence plasmid encoding the SpvB actin cytotoxin required for systemic survival and Pef fimbriae, implicated in adherence to the murine intestinal epithelium. All (21 of 21) serovar Typhimurium clinical isolates derived from animals were virulent in mice, whereas many (16 of 41) serovar Typhimurium isolates derived from human salmonellosis patients lacked this capacity. Additionally, many (10 of 29) serovar Typhimurium isolates derived from gastroenteritis patients did not possess the Salmonella virulence plasmid, in contrast to all animal and human bacteremia isolates tested. Lastly, among serovar Typhimurium isolates that harbored the Salmonella virulence plasmid, 6 of 31 derived from human salmonellosis patients were avirulent in mice, which is in contrast to the virulent phenotype exhibited by all the animal isolates examined. These studies suggest that Salmonella isolates derived from human salmonellosis patients are distinct from those of animal origin. The characterization of these bacterial strain variants may provide insight into their relative pathogenicities as well as into the development of treatment and prophylactic strategies for salmonellosis. PMID:18245251

Heithoff, Douglas M; Shimp, William R; Lau, Patrick W; Badie, Golnaz; Enioutina, Elena Y; Daynes, Raymond A; Byrne, Barbara A; House, John K; Mahan, Michael J

2008-03-01

98

Fine mapping of a replication origin of human DNA.  

PubMed Central

A highly sensitive procedure was developed for the identification of the origin of bidirectional DNA synthesis in single-copy replicons of mammalian cells. The method, which does not require cell synchronization or permeabilization, entails the absolute quantification, by a competitive PCR procedure in newly synthesized DNA samples, of the abundance of neighboring DNA fragments distributed along a given genomic region. This procedure was utilized for mapping the start site of DNA replication in a 13.7-kb region of human chromosome 19 coding for lamin B2, which is replicated immediately after the onset of S phase in HL-60 cells. Within this region, DNA replication initiates in a 474-bp area corresponding to the 3' noncoding end of the lamin B2 gene and the nontranscribed spacer between this gene and the 5' end of another highly transcribed one. This localization was obtained both in aphidicolin-synchronized and in exponentially growing HL-60 cells. Images

Giacca, M; Zentilin, L; Norio, P; Diviacco, S; Dimitrova, D; Contreas, G; Biamonti, G; Perini, G; Weighardt, F; Riva, S

1994-01-01

99

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

ERIC Educational Resources Information Center

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,"…

Isaacson, Emily Ruth

2013-01-01

100

Can Chimpanzee Biology Highlight Human Origin and Evolution?  

PubMed Central

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.

Roffman, Itai; Nevo, Eviatar

2010-01-01

101

Short faces, big tongues: developmental origin of the human chin.  

PubMed

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--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

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

2013-01-01

102

Genome-wide studies highlight indirect links between human replication origins and gene regulation  

Microsoft Academic Search

To get insights into the regulation of replication initiation, we systematically mapped replication origins along 1% of the human genome in HeLa cells. We identified 283 origins, 10 times more than previously known. Origin density is strongly correlated with genomic landscapes, with clusters of closely spaced origins in GC-rich regions and no origins in large GC-poor regions. Origin sequences are

Jean-Charles Cadoret; Françoise Meisch; Vahideh Hassan-Zadeh; Isabelle Luyten; Claire Guillet; Laurent Duret; Hadi Quesneville; Marie-Noëlle Prioleau

2008-01-01

103

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

PubMed

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

Jalobeanu, Dana

2012-01-01

104

Least effort and the origins of scaling in human language  

PubMed Central

The emergence of a complex language is one of the fundamental events of human evolution, and several remarkable features suggest the presence of fundamental principles of organization. These principles seem to be common to all languages. The best known is the so-called Zipf's law, which states that the frequency of a word decays as a (universal) power law of its rank. The possible origins of this law have been controversial, and its meaningfulness is still an open question. In this article, the early hypothesis of Zipf of a principle of least effort for explaining the law is shown to be sound. Simultaneous minimization in the effort of both hearer and speaker is formalized with a simple optimization process operating on a binary matrix of signal–object associations. Zipf's law is found in the transition between referentially useless systems and indexical reference systems. Our finding strongly suggests that Zipf's law is a hallmark of symbolic reference and not a meaningless feature. The implications for the evolution of language are discussed. We explain how language evolution can take advantage of a communicative phase transition.

Cancho, Ramon Ferrer i; Sole, Ricard V.

2003-01-01

105

Anne E. C. McCants - Goods at Pawn: The Overlapping Worlds of Material Possessions and Family Finance in Early Modern Amsterdam - Social Science History 31:2  

Microsoft Academic Search

The pawnshop was a critical component of urban credit networks in early modern Europe, serving as a source of ready cash in an era before there was widespread access to deposit banking and formal consumer loans. This article examines the use of the pawnshop, among other financial strategies, such as shop credit and loans between kin and neighbors, by a

Anne E. C. McCants

2007-01-01

106

Genome-wide studies highlight indirect links between human replication origins and gene regulation  

PubMed Central

To get insights into the regulation of replication initiation, we systematically mapped replication origins along 1% of the human genome in HeLa cells. We identified 283 origins, 10 times more than previously known. Origin density is strongly correlated with genomic landscapes, with clusters of closely spaced origins in GC-rich regions and no origins in large GC-poor regions. Origin sequences are evolutionarily conserved, and half of them map within or near CpG islands. Most of the origins overlap transcriptional regulatory elements, providing further evidence of a connection with gene regulation. Moreover, we identify c-JUN and c-FOS as important regulators of origin selection. Half of the identified replication initiation sites do not have an open chromatin configuration, showing the absence of a direct link with gene regulation. Replication timing analyses coupled with our origin mapping suggest that a relatively strict origin-timing program regulates the replication of the human genome.

Cadoret, Jean-Charles; Meisch, Francoise; Hassan-Zadeh, Vahideh; Luyten, Isabelle; Guillet, Claire; Duret, Laurent; Quesneville, Hadi; Prioleau, Marie-Noelle

2008-01-01

107

The origin of bursts and heavy tails in human dynamics  

Microsoft Academic Search

The dynamics of many social, technological and economic phenomena are driven by individual human actions, turning the quantitative understanding of human behavior into a central question of modern science. Current models of human dynamics, used from risk assessment to communications, assume that human actions are randomly distributed in time and thus well approximated by Poisson processes (1, 2, 3). In

Albert-Laszlo Barabasi

2005-01-01

108

Geometric variation of the frontal squama in the genus homo: frontal bulging and the origin of modern human morphology.  

PubMed

The majority of studies of frontal bone morphology in paleoanthropology have analyzed the frontal squama and the browridge as a single unit, mixing information from different functional elements. Taking into account that the bulging of the frontal bone is often described as a species-specific trait of Homo sapiens, in this article we analyze variation in the midsagittal profile of the genus Homo, focusing on the frontal squama alone, using landmark-based superimpositions and principal components analysis. Our results demonstrate that anatomically modern humans are definitely separated from extinct human taxa on the basis of frontal bulging. However, there is minor overlap among these groups, indicating that it is necessary to exercise caution when using this trait alone to make taxonomic inferences on individual specimens. Early modern humans do not show differences with recent modern humans, and "transitional" individuals such as Jebel Irhoud 1, Maba, and Florisbad, show modern-like frontal squama morphology. The bulging of the frontal squama in modern humans may represent a structural consequence of more general cranial changes, or it could be a response to changes in the morphology of the underlying prefrontal brain elements. A subtle difference between Neandertals and the Afro-European Middle Pleistocene Homo sample is associated with flattening at bregma in the former group, a result that merits further investigation. PMID:23292748

Bruner, Emiliano; Athreya, Sheela; de la Cuétara, José Manuel; Marks, Tarah

2013-02-01

109

Recombination of Influenza A Viruses of Human and Animal Origin  

Microsoft Academic Search

Simultaneous infection of the allantoic sac of the chick embryo with influenza A\\/equine 1\\/56 and any of three recombinants derived from human influenza viruses produced stable hybrids with antigens from each parent strain. These hybrids contain the hemagglutinin protein of the equine virus and the neuraminidase of the human strains. The experiments demonstrate genetic homology of human and equine influenza

Edwin D. Kilbourne

1968-01-01

110

Activation of a human chromosomal replication origin by protein tethering  

PubMed Central

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.

Chen, Xiaomi; Liu, Guoqi; Leffak, Michael

2013-01-01

111

Genomic signatures of diet-related shifts during human origins  

PubMed Central

There are numerous anthropological analyses concerning the importance of diet during human evolution. Diet is thought to have had a profound influence on the human phenotype, and dietary differences have been hypothesized to contribute to the dramatic morphological changes seen in modern humans as compared with non-human primates. Here, we attempt to integrate the results of new genomic studies within this well-developed anthropological context. We then review the current evidence for adaptation related to diet, both at the level of sequence changes and gene expression. Finally, we propose some ways in which new technologies can help identify specific genomic adaptations that have resulted in metabolic and morphological differences between humans and non-human primates.

Babbitt, Courtney C.; Warner, Lisa R.; Fedrigo, Olivier; Wall, Christine E.; Wray, Gregory A.

2011-01-01

112

Socio-cultural factors in dental diseases in the Medieval and early Modern Age of northern Spain.  

PubMed

The aim of this study is to present, discuss and compare the results of pathological conditions in teeth from skeletal remains found in the northern part of the Iberian Peninsula (Spain) in four Medieval cemeteries (late 15th century) and three cemeteries from the Modern Age (late 18th century). The final objective was to evaluate the impact of socioeconomic and cultural changes that took place during the early Modern Age in Spain, on oral health. Dental caries and antemortem tooth loss were considered as indicators of dental disease. A significant increase of both dental caries and antemortem tooth loss occurred in Modern Age individuals when compared to Medieval values, as reported for other regions. Increased trade with other continents may explain this deterioration of dental health, as food exchanges (mainly with America) contributed to diet changes for the overall population, including higher carbohydrate consumption (introduction of potatoes) at the expense of other vegetables. A sex-specific increase of dental disease with age, and a significantly higher prevalence of carious lesions in Modern Age females than in males, were also found. These changes can be explained by women having had limited access to dental care after the Middle-Modern Age transition, as a consequence of socio-cultural and political changes. In these changes, an increasing influence of the Catholic Church in Spanish society has to be noted, as it can contribute to the explanation of the unequal dental health of men and women. Women were socially excluded from dental care by regulations inspired by religious precepts. PMID:22265008

Lopez, Belen; Pardiñas, Antonio F; Garcia-Vazquez, Eva; Dopico, Eduardo

2012-02-01

113

Human social origins: Oh please, tell us another story  

Microsoft Academic Search

This paper aims at a rigorous comparison between accounts of the origins and evolution of society. Since the paper is a collaboration between a sociologist and a primatologist. the list of accounts includes political philosophers and social theorists as well as modern sociobiologists and anthopologists. In order to make the comparison possible, a ques- tionnaire was devised which clearly spells

B. Latour; S STRUM

1986-01-01

114

Origins of the Human Pointing Gesture: A Training Study  

ERIC Educational Resources Information Center

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…

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

2012-01-01

115

Warfare, Economic Performance And The Struggle For World Hegemony In The Early Modern Period: Guns Versus Butter In Eighteenth-Century Britain And Spain  

Microsoft Academic Search

Testing the existence of budgetary trade-offs in eighteenth-century Britain and Spain can contribute to resolve the debate on the economic impact of warfare and its relationships with the military potential of nations and the struggle for world supremacy during the early modern period. We have constructed several empirical models to search for trade-offs in order to show which country had

José Jurado-Sánchez; Miguel Jerez-Méndez

2011-01-01

116

Warfare, Economic Performance And The Struggle For World Hegemony In The Early Modern Period: Guns Versus Butter In Eighteenth-Century Britain And Spain  

Microsoft Academic Search

Testing the existence of budgetary trade-offs in eighteenth-century Britain and Spain can contribute to resolve the debate on the economic impact of warfare and its relationships with the military potential of nations and the struggle for world supremacy during the early modern period. We have constructed several empirical models to search for trade-offs in order to show which country had

José Jurado-Sánchez; Miguel Jerez-Méndez

2012-01-01

117

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

PubMed Central

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.

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

2006-01-01

118

Neandertal DNA Sequences and the Origin of Modern Humans  

Microsoft Academic Search

DNA was extracted from the Neandertal-type specimen found in 1856 in western Germany. By sequencing clones from short overlapping PCR products, a hitherto unknown mitochondrial (mt) DNA sequence was determined. Multiple controls indicate that this sequence is endogenous to the fossil. Sequence comparisons with human mtDNA sequences, as well as phylogenetic analyses, show that the Neandertal sequence falls outside the

Matthias Krings; Anne Stone; Ralf W. Schmitz; Heike Krainitzki; Mark Stoneking; Svante Pääbo

1997-01-01

119

Electrostatic origin of in vitro aggregation of human ?-crystallin.  

PubMed

The proteins ?-, ?-, and ?-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 ?-crystallin and ?-crystallin. We find that ?-crystallin spontaneously aggregates into finite-sized clusters in phosphate buffer solutions. There are two distinct populations of unaggregated and aggregated ?-crystallins in these solutions. On the other hand, ?-crystallin molecules are not aggregated into large clusters in solutions of ?-crystallin alone. When ?-crystallin and ?-crystallin are mixed in phosphate buffer solutions, we demonstrate that the clusters of ?-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 ?-crystallin under our in vitro conditions arises from non-covalent electrostatic interactions. In addition, we show that aggregation of ?-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 ?-crystallin when maintained under reducing conditions suggests that oxidation does not contribute to the aggregation in dilute solutions. PMID:24089726

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

2013-09-28

120

The human socio-cognitive niche and its evolutionary origins  

PubMed Central

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.

Whiten, Andrew; Erdal, David

2012-01-01

121

The First Humans: A Summary Perspective on the Origin and Early Evolution of the Genus Homo  

Microsoft Academic Search

Origin, adaptation and diversity are eternal themes in human evolution. These issues are equally timeless with respect to\\u000a our own lineage. Human paleontologists continue to grapple with questions surrounding the origin and early evolution of our\\u000a own genus. How do we identify the earliest members the genus Homo? How many species of Homo were there in the Pliocene and Pleistocene,

Frederick E. Grine; John G. Fleagle

122

Mitochondrial DNA and the origin of humans, Douglas WallaceSite: DNA Interactive (www.dnai.org)  

NSDL National Science Digital Library

Interviewee: Douglas Wallace DNAi Location:Applications>Human origins>migrations>Videos Mitochondrial DNA research pioneer Douglas Wallace speaks about mitochondrial DNA and theories of human evolution.

2008-10-06

123

Identification of a Binding Region for Human Origin Recognition Complex Proteins 1 and 2 That Coincides with an Origin of DNA Replication  

Microsoft Academic Search

We investigated the binding regions of components of the origin recognition complex (ORC) in the human genome. For this purpose, we performed chromatin immunoprecipitation assays with antibodies against human Orc1 and Orc2 proteins. We identified a binding region for human Orc proteins 1 and 2 in a <1-kbp segment between two divergently transcribed human genes. The region is characterized by

Eva-Maria Ladenburger; Christian Keller; Rolf Knippers

2002-01-01

124

The origin of remarkable resilience of human tooth enamel  

NASA Astrophysics Data System (ADS)

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.

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

2013-12-01

125

The fossil trade: paying a price for human origins.  

PubMed

Fossils have been traded for centuries. Over the past two hundred years the market has developed into an organized enterprise, with fossils serving multiple functions as objects of scientific study, collectors' items, and investments. Finding fossils, digging them up or purchasing them, transporting, studying, and conserving them, and putting them on display was and still is expensive. Since the early nineteenth century, funding bodies, academic institutions and museums, philanthropists, dealers, collectors, amateurs, and professional paleontologists have constituted elaborate networks driven by collaboration, necessity, ambition, accolades, and capital to generate knowledge and produce geological artifacts, increasing our understanding of the natural world, advancing careers and institutions, and contributing to personal fortunes. The emergence of paleoanthropology as a scientific discipline around 1900 generated a scientific focus on the human story that was easy to sell. The scarcity of ancient human remains made it close to impossible for a commercial market to evolve, yet finding them required serious funding. Elaborate schemes for financing expeditions and excavations went hand in hand with individual aspirations, patronage, philanthropy, networks, and alliance building, as concession rights and access to sponsors were objects of regular political intrigues and often bitter disputes. PMID:22908426

Kjoergaard, Peter C

2012-06-01

126

A cancer stem cell origin for human endometrial carcinoma?  

PubMed

Endometrial cancer (EC) is the most common gynaecological malignancy affecting women in the western world. Cancer stem cells (CSCs) are defined as a subset of tumour cells with the capacity to self-renew and give rise to the differentiated cells that comprise the bulk of the tumour. Given that a rare population of epithelial stem/progenitor cells has been identified in human endometrium, it is possible that these cells or their progeny may be the source of the putative CSCs that may initiate and maintain EC. Studies have shown that some cells within EC have the capacity to initiate clones that undergo self-renewing cell division and form tumours in vivo that can be serially passaged, demonstrating self-renewal, proliferation and differentiation abilities of the potential EC stem cells (ECSCs). These potential ECSCs may be located within the tumour cell population expressing CD133 and/or within the side population. With the discovery of markers for ECSCs, it is hoped that ECSCs can be isolated and characterised, and that their role in the development of human EC will be further investigated. This knowledge opens the way for the development of new treatment modalities that target the CSCs, but spares normal endometrial stem/progenitor cells and other cells. Such treatments will be particularly useful for early-stage and pre-menopausal EC candidates where the uterus may be conserved, and for late-stage cases where hysterectomy is not curative and current treatments target the bulk tumour cells rather than CSCs. PMID:20089663

Hubbard, Sonya A; Gargett, Caroline E

2010-07-01

127

Human origins family treeSite: DNA Interactive (www.dnai.org)  

NSDL National Science Digital Library

DNAi Location:Applications>Human origins>our family tree Meet the extended family Until the late 1900s, many researchers believed that humans evolved from an apelike ancestor through a linear series of stages. There are now many different theories about the relationships between species. It appears that we may just be one of the twigs on a vast family tree.

2009-04-10

128

Clonal origin of human erythro-eosinophilic colonies in culture.  

PubMed

We have observed the presence of erythropoietic bursts containing eosinophils and their precursors in methylcellulose culture of human peripheral blood and marrow nucleated cells in the presence of erythropoietin and medium conditioned by phytohemagglutinin-stimulated leukocytes (PHA-LCM). It was possible to identify these bursts (colonies) in situ in methylcellulose culture on the basis of their unique red and black colors. Transmission electron microscopy revealed that the constituent erythroid and eosinophilic cells lay intermixed with each other, and through close intercellular connections formed compact colonies and bursts consisting of several sub-colonies. Differential counts of individual erythro-eosinophil colonies (EEo colonies) revealed only a small percentage of blast cells in most of the colonies. Replating experiments of single EEo colonies yielded only eosinophilic colonies and clusters and erythroid colonies. The clonal nature of the EEo colonies was documented by analysis of Y-chromatin-positive cells in individual EEo colonies derived from cocultures of male and female peripheral blood mononuclear cells. Comparison of conditioned media indicated that PHA-LCM is the best stimulator for EEo colonies. These studies suggest that the differentiation capabilities of the progenitors for EEo colonies are restricted to erythroid and eosinophilic differentiation. PMID:7059681

Nakahata, T; Spicer, S S; Ogawa, M

1982-04-01

129

On the origins of suboptimality in human probabilistic inference.  

PubMed

Humans have been shown to combine noisy sensory information with previous experience (priors), in qualitative and sometimes quantitative agreement with the statistically-optimal predictions of Bayesian integration. However, when the prior distribution becomes more complex than a simple Gaussian, such as skewed or bimodal, training takes much longer and performance appears suboptimal. It is unclear whether such suboptimality arises from an imprecise internal representation of the complex prior, or from additional constraints in performing probabilistic computations on complex distributions, even when accurately represented. Here we probe the sources of suboptimality in probabilistic inference using a novel estimation task in which subjects are exposed to an explicitly provided distribution, thereby removing the need to remember the prior. Subjects had to estimate the location of a target given a noisy cue and a visual representation of the prior probability density over locations, which changed on each trial. Different classes of priors were examined (Gaussian, unimodal, bimodal). Subjects' performance was in qualitative agreement with the predictions of Bayesian Decision Theory although generally suboptimal. The degree of suboptimality was modulated by statistical features of the priors but was largely independent of the class of the prior and level of noise in the cue, suggesting that suboptimality in dealing with complex statistical features, such as bimodality, may be due to a problem of acquiring the priors rather than computing with them. We performed a factorial model comparison across a large set of Bayesian observer models to identify additional sources of noise and suboptimality. Our analysis rejects several models of stochastic behavior, including probability matching and sample-averaging strategies. Instead we show that subjects' response variability was mainly driven by a combination of a noisy estimation of the parameters of the priors, and by variability in the decision process, which we represent as a noisy or stochastic posterior. PMID:24945142

Acerbi, Luigi; Vijayakumar, Sethu; Wolpert, Daniel M

2014-06-01

130

On the Origins of Suboptimality in Human Probabilistic Inference  

PubMed Central

Humans have been shown to combine noisy sensory information with previous experience (priors), in qualitative and sometimes quantitative agreement with the statistically-optimal predictions of Bayesian integration. However, when the prior distribution becomes more complex than a simple Gaussian, such as skewed or bimodal, training takes much longer and performance appears suboptimal. It is unclear whether such suboptimality arises from an imprecise internal representation of the complex prior, or from additional constraints in performing probabilistic computations on complex distributions, even when accurately represented. Here we probe the sources of suboptimality in probabilistic inference using a novel estimation task in which subjects are exposed to an explicitly provided distribution, thereby removing the need to remember the prior. Subjects had to estimate the location of a target given a noisy cue and a visual representation of the prior probability density over locations, which changed on each trial. Different classes of priors were examined (Gaussian, unimodal, bimodal). Subjects' performance was in qualitative agreement with the predictions of Bayesian Decision Theory although generally suboptimal. The degree of suboptimality was modulated by statistical features of the priors but was largely independent of the class of the prior and level of noise in the cue, suggesting that suboptimality in dealing with complex statistical features, such as bimodality, may be due to a problem of acquiring the priors rather than computing with them. We performed a factorial model comparison across a large set of Bayesian observer models to identify additional sources of noise and suboptimality. Our analysis rejects several models of stochastic behavior, including probability matching and sample-averaging strategies. Instead we show that subjects' response variability was mainly driven by a combination of a noisy estimation of the parameters of the priors, and by variability in the decision process, which we represent as a noisy or stochastic posterior.

Acerbi, Luigi; Vijayakumar, Sethu; Wolpert, Daniel M.

2014-01-01

131

Spatial Dynamics of Human-Origin H1 Influenza A Virus in North American Swine  

Microsoft Academic Search

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

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

2011-01-01

132

Embryonic origins of human vascular smooth muscle cells: implications for in vitro modeling and clinical application.  

PubMed

Vascular smooth muscle cells (SMCs) arise from multiple origins during development, raising the possibility that differences in embryological origins between SMCs could contribute to site-specific localization of vascular diseases. In this review, we first examine the developmental pathways and embryological origins of vascular SMCs and then discuss in vitro strategies for deriving SMCs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We then review in detail the potential for vascular disease modeling using iPSC-derived SMCs and consider the pathological implications of heterogeneous embryonic origins. Finally, we touch upon the role of human ESC-derived SMCs in therapeutic revascularization and the challenges remaining before regenerative medicine using ESC- or iPSC-derived cells comes of age. PMID:24442477

Sinha, Sanjay; Iyer, Dharini; Granata, Alessandra

2014-06-01

133

The contribution of dormant origins to genome stability: From cell biology to human genetics  

PubMed Central

The ability of a eukaryotic cell to precisely and accurately replicate its DNA is crucial to maintain genome stability. Here we describe our current understanding of the process by which origins are licensed for DNA replication and review recent work suggesting that fork stalling has exerted a strong selective pressure on the positioning of licensed origins. In light of this, we discuss the complex and disparate phenotypes observed in mouse models and humans patients that arise due to defects in replication licensing proteins.

Alver, Robert C.; Chadha, Gaganmeet Singh; Blow, J. Julian

2014-01-01

134

Presence of drug resistance in intestinal lactobacilli of dairy and human origin in Turkey  

Microsoft Academic Search

The prevalence of different resistance genes was investigated in lactobacilli of human and dairy origin by PCR. The presence of erm, van, tet, and cat-TC genes were determined in 16 raw milk, 15 cream, 10 yogurt, 50 hand-made cheese, and 20 industrially produced white-cheese samples of dairy origin and 16 mouth, 32 fecal, and 36 vaginal samples from different subjects

Osman Çataloluk; Bulent Gogebakan

2004-01-01

135

Origin and evolution of a placental-specific microRNA family in the human genome  

Microsoft Academic Search

BACKGROUND: MicroRNAs (miRNAs) are a class of short regulatory RNAs encoded in the genome of DNA viruses, some single cell organisms, plants and animals. With the rapid development of technology, more and more miRNAs are being discovered. However, the origin and evolution of most miRNAs remain obscure. Here we report the origin and evolution dynamics of a human miRNA family.

Zhidong Yuan; Xiao Sun; Dongke Jiang; Yan Ding; Zhiyuan Lu; Lejun Gong; Hongde Liu; Jianming Xie

2010-01-01

136

Presence of drug resistance in intestinal lactobacilli of dairy and human origin in Turkey.  

PubMed

The prevalence of different resistance genes was investigated in lactobacilli of human and dairy origin by PCR. The presence of erm, van, tet, and cat-TC genes were determined in 16 raw milk, 15 cream, 10 yogurt, 50 hand-made cheese, and 20 industrially produced white-cheese samples of dairy origin and 16 mouth, 32 fecal, and 36 vaginal samples from different subjects of human origin. Lactobacilli of dairy and human origin were found to carry only erm(B) and tet(M) genes. The majority of the isolates, Lactobacillus crispatus (61), Lactobacillus gasseri (49), Lactobacillus plantarum (80) studied were found to harbor either erm(B) or tet(M) gene or both. No resistant lactobacilli was found in raw-milk and cream samples. All the human fecal samples and the majority of vaginal (29 of 36) and mouth (10 of 14) samples were found to carry the resistance genes. While a third of the hand-made cheeses carried resistant lactobacilli only one industrially produced cheese was found to carry resistant lactobacilli. Furthermore, the genes were found in the non-starter species, Lactobacillus acidophilus and Lb. plantarum, indicating that industrially produced cheeses in this respect could be considered more favorable. These results indicate that drug resistance seems to be very common in Turkey. Even though the number of dairy samples harboring the resistance genes (17 of 111) is smaller in regards to human samples, 10% of them were still found to carry the resistance genes as well. The presence of the resistance genes in majority of the samples of human origin and in minority of the samples of dairy origin indicates that drug resistance may be acquired in the intestinal tract during passage and spread to dairy products by the hands of workers during production. PMID:15212784

Cataloluk, Osman; Gogebakan, Bulent

2004-07-01

137

The conditional returns to origin-country human capital among Turkish and Moroccan immigrants in Belgium.  

PubMed

This study extends the analysis of the economic returns to pre-migration human capital by examining the role of the receiving context, co-ethnic residential concentration, and post-migration investments in human capital. It uses large-scale survey data on Turkish and Moroccan immigrants in Belgium. The analysis demonstrates that regarding employment, Moroccan immigrants, that is, those originating from former French colonies receive larger returns to their origin-country education and work experience in French- vs. Dutch-speaking regions. Other than the positive interaction effect between co-ethnic residential concentration and work experience on employment, there is little evidence that co-ethnic concentration increases the returns to origin-country human capital. Speaking the host-country language facilitates economic returns to origin-country work experience. Conversely, immigrants who acquire host-country credentials and work experience receive lower returns to origin-country education and experience, suggesting that, at least among low-skilled immigrants, pre- and post-migration human capital substitute rather than complement each other. PMID:24767595

Kanas, Agnieszka; van Tubergen, Frank

2014-07-01

138

Discrimination between Bifidobacterium species from human and animal origin by PCR-restriction fragment length polymorphism.  

PubMed

Bifidobacteria are normal intestinal flora in humans and animals. The genus Bifidobacterium includes 31 species of significant host specificity. Taking into account their properties, we proposed to use bifidobacteria as fecal contamination indicators. PCR-restriction fragment length polymorphism on the 16S rDNA gene was used to distinguish the different Bifidobacterium species. Sixty-four strains belonging to 13 different species were differentiated from animal or human origin using one or two restriction enzymes. Moreover, the primers used were specifics of the Bifidobacterium genus. Therefore, this method made it possible to determine both the presence of bifidobacteria in a sample and its origin of contamination. PMID:15222566

Delcenserie, V; Bechoux, N; Léonard, T; China, B; Daube, G

2004-06-01

139

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

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…

Zachlod, Michelle, Ed.

140

Human memory B cells originate from three distinct germinal center-dependent and -independent maturation pathways  

PubMed Central

Multiple distinct memory B-cell subsets have been identified in humans, but it remains unclear how their phenotypic diversity corresponds to the type of responses from which they originate. Especially, the contribution of germinal center-independent responses in humans remains controversial. We defined 6 memory B-cell subsets based on their antigen-experienced phenotype and differential expression of CD27 and IgH isotypes. Molecular characterization of their replication history, Ig somatic hypermutation, and class-switch profiles demonstrated their origin from 3 different pathways. CD27?IgG+ and CD27+IgM+ B cells are derived from primary germinal center reactions, and CD27+IgA+ and CD27+IgG+ B cells are from consecutive germinal center responses (pathway 1). In contrast, natural effector and CD27?IgA+ memory B cells have limited proliferation and are also present in CD40L-deficient patients, reflecting a germinal center-independent origin. Natural effector cells at least in part originate from systemic responses in the splenic marginal zone (pathway 2). CD27?IgA+ cells share low replication history and dominant Ig? and IgA2 use with gut lamina propria IgA+ B cells, suggesting their common origin from local germinal center-independent responses (pathway 3). Our findings shed light on human germinal center-dependent and -independent B-cell memory formation and provide new opportunities to study these processes in immunologic diseases.

Berkowska, Magdalena A.; Driessen, Gertjan J. A.; Bikos, Vasilis; Grosserichter-Wagener, Christina; Stamatopoulos, Kostas; Cerutti, Andrea; He, Bing; Biermann, Katharina; Lange, Johan F.; van der Burg, Mirjam; van Dongen, Jacques J. M.

2011-01-01

141

IS Sag1 in streptococcal strains of human and animal origin  

Microsoft Academic Search

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

Carmen Franken; Claudia Brandt; Gerd Bröker; Barbara Spellerberg

2004-01-01

142

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

PubMed Central

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”.

De Preester, Helena; Tsakiris, Manos

2014-01-01

143

A General Theory Concerning the Prenatal Origins of Cerebral Lateralization in Humans  

Microsoft Academic Search

The origins of cerebral lateralization in humans are traced to the asymmetric prenatal development of the ear and labyrinth. Aural lateralization is hypothesized to result from an asymmetry in craniofacial development, whereas vestibular dominance is traced to the position of the fetus during the final trimester. A right-ear sensitivity advantage may contribute to a left-hemispheric advantage in speech perception and

Fred H. Previc

1991-01-01

144

Origins of XMRV deciphered, undermining claims for a role in human disease  

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.

145

Identification and functional analysis of a human homologue of the monkey replication origin ors8.  

PubMed

We previously isolated from African green monkey (CV-1) cells a replication origin, ors8, that is active at the onset of S-phase. Here, its homologous sequence (hors8, accession number: DQ230978) was amplified from human cells, using the monkey-ors8-specific primers. Sequence alignment between the monkey and the human fragment revealed a 92% identity. Nascent DNA abundance analysis, involving quantification by real-time PCR, indicated that hors8 is an active replication origin, as the abundance of nascent DNA from a genomic region containing it was 97-fold higher relative to a non-origin region in the same locus. Furthermore, the data showed that the hors8 fragment is capable of supporting the episomal replication of its plasmid, when cloned into pBlueScript (pBS), as assayed by the DpnI resistance assay after transfection of HeLa cells. A quantitative chromatin immunoprecipitation (ChIP) assay, using antibodies against Ku, Orc2, and Cdc6, showed that these DNA replication initiator proteins were associated in vivo with the human ors8 (hors8). Finally, nascent DNA abundance experiments from human cells synchronized at different phases of the cell cycle revealed that hors8 is a late-firing origin of DNA replication, having the highest activity 8 h after release from late G(1). PMID:16823771

Callejo, Mario; Sibani, Sahar; Di Paola, Domenic; Price, Gerald G; Zannis-Hadjopoulos, Maria

2006-12-15

146

The Conflict of Pre-Paradigm Schools in Modern Human Origins Research  

Microsoft Academic Search

The debate on the origins of modern humans is one of the oldest and most controversial in the field of palaeoanthropology. In the 1860s the debate was established in the evolutionary context and, as a conflict between two major schools and various sub-schools, it has continued up until the present day. The opposing schools were and still are, at best,

Goran Strkalj

2000-01-01

147

On the reliability of recent tests of the Out of Africa hypothesis for modern human origins  

Microsoft Academic Search

In this paper we critique two recent studies that have been claimed to disprove the Out of Africa hypothesis for modern human origins (Hawks et al., 2000; Wolpoff et al., 2001). We show that the test prediction employed by Hawks et al. (2000) and Wolpff et al. (2001) is not relevant to many versions of the Out of Africa hypothesis,

GUNTER BRAUER; Mark Collard; Chris Stringer

2004-01-01

148

Pharmacology of an original and selective nonpeptide antagonist ligand for the human tachykinin NK 2 receptor  

Microsoft Academic Search

The pharmacological outline of a novel and original antagonist at the human tachykinin NK2 receptor is presented, namely MEN13510 (N-N?-bis-[2-(1H-indol-3-yl)-ethyl]-N,N?-bis-(3-thiomorpholin-4-yl-propyl)-phthalamide). MEN13510 retained nanomolar affinity for the human tachykinin NK2 receptor (Ki 6.4 nM), and micromolar affinity for the human tachykinin NK1 and NK3 receptors. A competitive antagonism is indicated by the Schild analysis (pKB 7.8, slope ?0.94) of concentration–response curves

Stefania Meini; Claudio Catalani; Francesca Bellucci; Paola Cucchi; Sandro Giuliani; Sabrina Zappitelli; Luigi Rotondaro; Franco Pasqui; Antonio Guidi; Maria Altamura; Alessandro Giolitti; Carlo Alberto Maggi

2005-01-01

149

Directed differentiation of embryonic origin-specific vascular smooth muscle subtypes from human pluripotent stem cells.  

PubMed

Vascular smooth muscle cells (SMCs) arise from diverse developmental origins. Regional distribution of vascular diseases may, in part, be attributed to this inherent heterogeneity in SMC lineage. Therefore, systems for generating human SMC subtypes of distinct embryonic origins would represent useful platforms for studying the influence of SMC lineage on the spatial specificity of vascular disease. Here we describe how human pluripotent stem cells can be differentiated into distinct populations of SMC subtypes under chemically defined conditions. The initial stage (days 0-5 or 0-7) begins with the induction of three intermediate lineages: neuroectoderm, lateral plate mesoderm and paraxial mesoderm. Subsequently, these precursor lineages are differentiated into contractile SMCs (days 5-19+). At key stages, the emergence of lineage-specific markers confirms recapitulation of embryonic developmental pathways and generation of functionally distinct SMC subtypes. The ability to derive an unlimited supply of human SMCs will accelerate applications in regenerative medicine and disease modeling. PMID:24675733

Cheung, Christine; Bernardo, Andreia S; Pedersen, Roger A; Sinha, Sanjay

2014-04-01

150

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

PubMed Central

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 40 years 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.

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

151

A monkey's tale: The origin of Plasmodium vivax as a human malaria parasite  

PubMed Central

The high prevalence of Duffy negativity (lack of the Duffy blood group antigen) among human populations in sub-Saharan Africa has been used to argue that Plasmodium vivax originated on that continent. Here, we investigate the phylogenetic relationships among 10 species of Plasmodium that infect primates by using three genes, two nuclear (?-tubulin and cell division cycle 2) and a gene from the plastid genome (the elongation factor Tu). We find compelling evidence that P. vivax is derived from a species that inhabited macaques in Southeast Asia. Specifically, those phylogenies that include P. vivax as an ancient lineage from which all of the macaque parasites could originate are significantly less likely to explain the data. We estimate the time to the most recent common ancestor at four neutral gene loci from Asian and South American isolates (a minimum sample of seven isolates per locus). Our analysis estimates that the extant populations of P. vivax originated between 45,680 and 81,607 years ago. The phylogeny and the estimated time frame for the origination of current P. vivax populations are consistent with an “out of Asia” origin for P. vivax as hominoid parasite. The current debate regarding how the Duffy negative trait became fixed in Africa needs to be revisited, taking into account not only human genetic data but also the genetic diversity observed in the extant P. vivax populations and the phylogeny of the genus Plasmodium.

Escalante, Ananias A.; Cornejo, Omar E.; Freeland, Denise E.; Poe, Amanda C.; Durrego, Ester; Collins, William E.; Lal, Altaf A.

2005-01-01

152

The contribution of dormant origins to genome stability: From cell biology to human genetics.  

PubMed

The ability of a eukaryotic cell to precisely and accurately replicate its DNA is crucial to maintain genome stability. Here we describe our current understanding of the process by which origins are licensed for DNA replication and review recent work suggesting that fork stalling has exerted a strong selective pressure on the positioning of licensed origins. In light of this, we discuss the complex and disparate phenotypes observed in mouse models and humans patients that arise due to defects in replication licensing proteins. PMID:24767947

Alver, Robert C; Chadha, Gaganmeet Singh; Blow, J Julian

2014-07-01

153

DNA Replication Timing Data Corroborate In Silico Human Replication Origin Predictions  

NASA Astrophysics Data System (ADS)

We develop a wavelet-based multiscale pattern recognition methodology to disentangle the replication- from the transcription-associated compositional strand asymmetries observed in the human genome. Comparing replication skew profiles to recent high-resolution replication timing data reveals that most of the putative replication origins that border the so-identified replication domains are replicated earlier than their surroundings whereas the central regions replicate late in the S phase. We discuss the implications of this first experimental confirmation of these replication origin predictions that are likely to be early replicating and active in most tissues.

Audit, B.; Nicolay, S.; Huvet, M.; Touchon, M.; D'Aubenton-Carafa, Y.; Thermes, C.; Arneodo, A.

2007-12-01

154

The Evolutionary Origin of Human Subtelomeric Homologies--or Where the Ends Begin  

PubMed Central

The subtelomeric regions of human chromosomes are comprised of sequence homologies shared between distinct subsets of chromosomes. In the course of developing a set of unique human telomere clones, we identified many clones containing such shared homologies, characterized by the presence of cross-hybridization signals on one or more telomeres in a fluorescence in situ hybridization (FISH) assay. We studied the evolutionary origin of seven subtelomeric clones by performing comparative FISH analysis on a primate panel that included great apes and Old World monkeys. All clones tested showed a single hybridization site in Old World monkeys that corresponded to one of the orthologous human sites, thus indicating the ancestral origin. The timing of the duplication events varied among the subtelomeric regions, from ?5 to ?25 million years ago. To examine the origin of and mechanism for one of these subtelomeric duplications, we compared the sequence derived from human 2q13—an ancestral fusion site of two great ape telomeric regions—with its paralogous subtelomeric sequences at 9p and 22q. These paralogous regions share large continuous homologies and contain three genes: RABL2B, forkhead box D4, and COBW-like. Our results provide further evidence for subtelomeric-mediated genomic duplication and demonstrate that these segmental duplications are most likely the result of ancestral unbalanced translocations that have been fixed in the genome during recent primate evolution.

Martin, Christa Lese; Wong, Andrew; Gross, Alyssa; Chung, June; Fantes, Judy A.; Ledbetter, David H.

2002-01-01

155

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

PubMed Central

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.

2013-01-01

156

Late Pleistocene Human Skull from Hofmeyr, South Africa, and Modern Human Origins  

Microsoft Academic Search

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

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

2007-01-01

157

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

PubMed

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-1 beta 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

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

2008-08-01

158

Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans  

Microsoft Academic Search

BACKGROUND On April 15 and April 17, 2009, novel swine-origin influenza A (H1N1) virus (S-OIV) was identified in specimens obtained from two epidemiologically unlinked patients in the United States. The same strain of the virus was identified in Mexico, Canada, and elsewhere. We describe 642 confirmed cases of human S-OIV infection identi- fied from the rapidly evolving U.S. outbreak. METHODS

Seema Jain; Lyn Finelli; Michael W. Shaw; Stephen Lindstrom; Rebecca J. Garten; Larisa V. Gubareva; Xiyan Xu; Carolyn B. Bridges; Timothy M. Uyeki

2009-01-01

159

Domesticated animals and human infectious diseases of zoonotic origins: Domestication time matters.  

PubMed

The rate of emergence for emerging infectious diseases has increased dramatically over the last century, and research findings have implicated wildlife as an importance source of novel pathogens. However, the role played by domestic animals as amplifiers of pathogens emerging from the wild could also be significant, influencing the human infectious disease transmission cycle. The impact of domestic hosts on human disease emergence should therefore be ascertained. Here, using three independent datasets we showed positive relationships between the time since domestication of the major domesticated mammals and the total number of parasites or infectious diseases they shared with humans. We used network analysis, to better visualize the overall interactions between humans and domestic animals (and amongst animals) and estimate which hosts are potential sources of parasites/pathogens for humans (and for all other hosts) by investigating the network architecture. We used centrality, a measure of the connection amongst each host species (humans and domestic animals) in the network, through the sharing of parasites/pathogens, where a central host (i.e. high value of centrality) is the one that is infected by many parasites/pathogens that infect many other hosts in the network. We showed that domesticated hosts that were associated a long time ago with humans are also the central ones in the network and those that favor parasites/pathogens transmission not only to humans but also to all other domesticated animals. These results urge further investigation of the diversity and origin of the infectious diseases of domesticated animals in their domestication centres and the dispersal routes associated with human activities. Such work may help us to better understand how domesticated animals have bridged the epidemiological gap between humans and wildlife. PMID:24642136

Morand, Serge; McIntyre, K Marie; Baylis, Matthew

2014-06-01

160

Comparative analysis of the genomes of intestinal spirochetes of human and animal origin.  

PubMed Central

The aim of the present work was to compare the genomes of 21 strains of intestinal spirochetes, which were isolated from patients suffering intestinal disorders, with those of Treponema hyodysenteriae (strain P18), the known etiological agent of swine dysentery (bloody scours), and of a nonpathogenic strain (M1) of Treponema innocens. The percent guanine-plus-cytosine value of the 23 DNAs was found to be 25.5 to 30.1, as determined by a double-labeling procedure based on nick-translation by DNA polymerase I. The genome size of two spirochetal strains, of human and porcine origin, was found to be similar (4 x 10(6) base pairs) and close to that of the reference bacterium Escherichia coli (4.2 x 10(6) base pairs). Restriction analysis showed the presence of two modified bases in spirochetal DNA. Methyladenine was present in the GATC sequence of DNA from 15 spirochetes of human origin, and methylcytosine was present in several sequences occurring in all strains. The DNA of T. hyodysenteriae displayed a 30 to 100% homology with respect to that of 21 spirochetes from humans, thus suggesting the occurrence of a genetic heterogeneity in the latter group. These data indicate that the intestinal spirochetes analyzed in the present work are related; hence there is a possibility of domestic animals being reservoirs of microorganisms pathogenic for humans. A classification of intestinal treponemes into subgroups has been proposed on the basis of restriction analysis and hybridization experiments. Images

Coene, M; Agliano, A M; Paques, A T; Cattani, P; Dettori, G; Sanna, A; Cocito, C

1989-01-01

161

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

PubMed

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

Beyin, Amanuel

2011-01-01

162

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

PubMed Central

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.

Beyin, Amanuel

2011-01-01

163

The idea of human prehistory: the natural sciences, the human sciences, and the problem of human origins in Victorian Britain.  

PubMed

The idea of human prehistory was a provocative and profoundly influential new notion that took shape gradually during the nineteenth century. While archaeology played an important role in providing the evidence for this idea many other sciences such as geology, paleontology, ethnology, and physical anthropology all made critical contributions to discussions about human prehistory. Many works have explored the history of prehistoric archaeology but this paper examines the conceptual content of the idea of "human prehistory" as it developed in the British scientific community. Both the natural and the human sciences contributed to what was in fact a complex collection of individual elements that together constituted the prevailing idea of human prehistory, although there were other competing conceptions of human prehistory endorsed by various scientists and critics of the new view of early human history. PMID:23272597

Goodrum, Matthew R

2012-01-01

164

Hunter-gatherer genomic diversity suggests a southern African origin for modern humans  

PubMed Central

Africa is inferred to be the continent of origin for all modern human populations, but the details of human prehistory and evolution in Africa remain largely obscure owing to the complex histories of hundreds of distinct populations. We present data for more than 580,000 SNPs for several hunter-gatherer populations: the Hadza and Sandawe of Tanzania, and the ?Khomani Bushmen of South Africa, including speakers of the nearly extinct N|u language. We find that African hunter-gatherer populations today remain highly differentiated, encompassing major components of variation that are not found in other African populations. Hunter-gatherer populations also tend to have the lowest levels of genome-wide linkage disequilibrium among 27 African populations. We analyzed geographic patterns of linkage disequilibrium and population differentiation, as measured by FST, in Africa. The observed patterns are consistent with an origin of modern humans in southern Africa rather than eastern Africa, as is generally assumed. Additionally, genetic variation in African hunter-gatherer populations has been significantly affected by interaction with farmers and herders over the past 5,000 y, through both severe population bottlenecks and sex-biased migration. However, African hunter-gatherer populations continue to maintain the highest levels of genetic diversity in the world.

Henn, Brenna M.; Gignoux, Christopher R.; Jobin, Matthew; Granka, Julie M.; Macpherson, J. M.; Kidd, Jeffrey M.; Rodriguez-Botigue, Laura; Ramachandran, Sohini; Hon, Lawrence; Brisbin, Abra; Lin, Alice A.; Underhill, Peter A.; Comas, David; Kidd, Kenneth K.; Norman, Paul J.; Parham, Peter; Bustamante, Carlos D.; Mountain, Joanna L.; Feldman, Marcus W.

2011-01-01

165

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

PubMed

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

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

1985-09-01

166

Early-Modern "Speech" Marks  

ERIC Educational Resources Information Center

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…

Blackburn, Nick

2011-01-01

167

Origin and primary dispersal of the Mycobacterium tuberculosis Beijing genotype: Clues from human phylogeography  

PubMed Central

We suggest that the evolution of the population structure of microbial pathogens is influenced by that of modern humans. Consequently, the timing of hallmark changes in bacterial genomes within the last 100,000 yr may be attempted by comparison with relevant human migrations. Here, we used a lineage within Mycobacterium tuberculosis, a Beijing genotype, as a model and compared its phylogeography with human demography and Y chromosome-based phylogeography. We hypothesize that two key events shaped the early history of the Beijing genotype: (1) its Upper Palaeolithic origin in the Homo sapiens sapiens K-M9 cluster in Central Asia, and (2) primary Neolithic dispersal of the secondary Beijing NTF::IS6110 lineage by Proto-Sino-Tibetan farmers within east Asia (human O-M214/M122 haplogroup). The independent introductions of the Beijing strains from east Asia to northern Eurasia and South Africa were likely historically recent, whereas their differential dissemination within these areas has been influenced by demographic and climatic factors.

Mokrousov, Igor; Ly, Ho Minh; Otten, Tatiana; Lan, Nguyen Ngoc; Vyshnevskyi, Boris; Hoffner, Sven; Narvskaya, Olga

2005-01-01

168

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

PubMed

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

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

169

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

PubMed Central

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.

Elhaik, Eran; Tatarinova, Tatiana; Chebotarev, Dmitri; Piras, Ignazio S.; Maria Calo, 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.; Gomez, Rocio; Fujita, Ricardo; Santos, Fabricio 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

170

Interactions of USF and Ku antigen with a human DNA region containing a replication origin.  

PubMed Central

By means of a combination of ion-exchange and sequence-specific affinity chromatography techniques, we have purified to homogeneity two protein complexes binding in a human DNA region (B48) previously recognized to contain a DNA replication origin. The DNA sequence used for the protein purification (B48 binding site) contains a binding site for basic-helix-loop-helix DNA binding proteins. The first complex is composed of two polypeptides of 42- and 44-kDa; its size, heat stability, and target DNA sequence suggest that it corresponds to transcription factor USF; furthermore, the 42-kDa polypeptide is recognized by antibodies raised against 43-kDa-USF. The second complex is represented by equimolar amounts of two proteins of 72 and 87 kDa; microsequencing of the two species indicated that they correspond to the human Ku antigen. In analogy with Ku, they produce a regular pattern of footprints without an apparent sequence-specificity, and their binding can be competed by unspecific DNA provided that it contains free ends. The potential role of B48 binding site and of these cognate proteins in origin activation is discussed. Images

Toth, E C; Marusic, L; Ochem, A; Patthy, A; Pongor, S; Giacca, M; Falaschi, A

1993-01-01

171

A View of Modern Human Origins from Y Chromosome Microsatellite Variation  

PubMed Central

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 (??)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.

Seielstad, Mark; Bekele, Endashaw; Ibrahim, Muntaser; Toure, Amadou; Traore, Mamadou

1999-01-01

172

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

PubMed

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

Seielstad, M; Bekele, E; Ibrahim, M; Touré, A; Traoré, M

1999-06-01

173

Pinnacle Point Cave 13B (Western Cape Province, South Africa) in context: The Cape Floral kingdom, shellfish, and modern human origins.  

PubMed

Genetic and anatomical evidence suggests that Homo sapiens arose in Africa between 200 and 100ka, and recent evidence suggests that complex cognition may have appeared between ~164 and 75ka. This evidence directs our focus to Marine Isotope Stage (MIS) 6, when from 195-123ka the world was in a fluctuating but predominantly glacial stage, when much of Africa was cooler and drier, and when dated archaeological sites are rare. Previously we have shown that humans had expanded their diet to include marine resources by ~164ka (±12ka) at Pinnacle Point Cave 13B (PP13B) on the south coast of South Africa, perhaps as a response to these harsh environmental conditions. The associated material culture documents an early use and modification of pigment, likely for symbolic behavior, as well as the production of bladelet stone tool technology, and there is now intriguing evidence for heat treatment of lithics. PP13B also includes a later sequence of MIS 5 occupations that document an adaptation that increasingly focuses on coastal resources. A model is developed that suggests that the combined richness of the Cape Floral Region on the south coast of Africa, with its high diversity and density of geophyte plants and the rich coastal ecosystems of the associated Agulhas Current, combined to provide a stable set of carbohydrate and protein resources for early modern humans along the southern coast of South Africa during this crucial but environmentally harsh phase in the evolution of modern humans. Humans structured their mobility around the use of coastal resources and geophyte abundance and focused their occupation at the intersection of the geophyte rich Cape flora and coastline. The evidence for human occupation relative to the distance to the coastline over time at PP13B is consistent with this model. PMID:20934095

Marean, Curtis W

2010-01-01

174

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

PubMed Central

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.

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

175

The origins of genetic variation between individual human oocytes and embryos: implications for infertility.  

PubMed

Human fertility is low in comparison with that seen in other well-studied mammals. The main reason for this state of affairs seems to be the frequent occurrence and persistence of chromosomal errors in the human conceptus. Evidence obtained over the past two decades shows that the exceptionally high incidence of chromosomal anomalies seen in human preimplantation embryos is the result of errors that may occur at various stages during gamete and embryo formation. In rare cases, an error may exist or arise in the premeiotic germ cells; much more commonly it may arise during the first or second meiotic division in the male or female. Highly efficient cell cycle checkpoints in the male ensure that the incidence of aneuploidy in mature sperm is low compared to that in the oocyte. Most 3-day-old embryos created by IVF are chromosomal mosaics, and this persists to a lesser degree to the blastocyst stage on day 5. While aneuploidy of meiotic origin is a major factor affecting the fertility of older women, embryos from most younger women will have predominantly post-zygotic mitotic errors. Couples experiencing RIF are particularly likely to produce highly abnormal (chaotic) embryos by post-zygotic mechanisms. PMID:24164188

Delhanty, Joy D A

2013-12-01

176

Pharmacology of an original and selective nonpeptide antagonist ligand for the human tachykinin NK2 receptor.  

PubMed

The pharmacological outline of a novel and original antagonist at the human tachykinin NK2 receptor is presented, namely MEN13510 (N-N'-bis-[2-(1H-indol-3-yl)-ethyl]-N,N'-bis-(3-thiomorpholin-4-yl-propyl)-phthalamide). MEN13510 retained nanomolar affinity for the human tachykinin NK2 receptor (Ki 6.4 nM), and micromolar affinity for the human tachykinin NK1 and NK3 receptors. A competitive antagonism is indicated by the Schild analysis (pK(B) 7.8, slope -0.94) of concentration-response curves of NKA induced inositolphosphates accumulation in Chinese hamster ovary (CHO) cells expressing the human NK2 receptor in the presence of MEN13510 (30-300 nM concentration range). The MEN13510 interaction with the human NK2 receptor was evaluated by means of heterologous inhibition binding experiments, by using agonist and antagonist radioligands ([125I]NKA, [3H]nepadutant, [3H]saredutant) at a series of mutant receptors having single aminoacidic substitutions of residues located in transmembrane (TM) segments 3, 4, 5, 6, and 7. MEN13510 affinity was not affected by the mutations in TM 3 and 4 (Q109A, F112A, T171A, C167G), and it was reduced by 10-fold at the I202F mutant, but not at the Y206A (TM4). Amongst the investigated mutants bearing the mutated residues in TM6 (F270A, Y266F, W263A) only F270A decreased the MEN13510 affinity by 7-fold. Even mutations in TM7 did reduce MEN13510 affinity by 32-fold (Y289T, but not Y289F) and 13-fold (F293A). Studied mutations represent the human tachykinin NK2 receptor discriminants involved in the binding of previously reported peptidic and nonpeptidic antagonists, against which results obtained with MEN13510 are compared. Results indicate that the binding site of this antagonist is, at least in part, overlapping to that described for NKA or saredutant. Finally we show that MEN13510 retains nanomolar affinity for the recently discovered splice variant of the human tachykinin NK2 receptor, namely beta isoform, as it has been described for the nonpeptide antagonist saredutant. PMID:15925360

Meini, Stefania; Catalani, Claudio; Bellucci, Francesca; Cucchi, Paola; Giuliani, Sandro; Zappitelli, Sabrina; Rotondaro, Luigi; Pasqui, Franco; Guidi, Antonio; Altamura, Maria; Giolitti, Alessandro; Maggi, Carlo Alberto

2005-06-01

177

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

PubMed

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

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

178

Spatial Dynamics of Human-Origin H1 Influenza A Virus in North American Swine  

PubMed Central

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.

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

2011-01-01

179

Localization of proteins bound to a replication origin of human DNA along the cell cycle.  

PubMed

The proteins bound in vivo at the human lamin B2 DNA replication origin and their precise sites of binding were investigated along the cell cycle utilizing two novel procedures based on immunoprecipitation following UV irradiation with a pulsed laser light source. In G(1), the pre-replicative complex contains CDC6, MCM3, ORC1 and ORC2 proteins; of these, the post-replicative complex in S phase contains only ORC2; in M phase none of them are bound. The precise nucleotide of binding was identified for the two ORC and the CDC6 proteins near the start sites for leading-strand synthesis; the transition from the pre- to the post-replicative complex is accompanied by a 17 bp displacement of the ORC2 protein towards the start site. PMID:12912926

Abdurashidova, Gulnara; Danailov, Miltcho B; Ochem, Alexander; Triolo, Gianluca; Djeliova, Vera; Radulescu, Sorina; Vindigni, Alessandro; Riva, Silvano; Falaschi, Arturo

2003-08-15

180

Localization of proteins bound to a replication origin of human DNA along the cell cycle  

PubMed Central

The proteins bound in vivo at the human lamin B2 DNA replication origin and their precise sites of binding were investigated along the cell cycle utilizing two novel procedures based on immunoprecipitation following UV irradiation with a pulsed laser light source. In G1, the pre-replicative complex contains CDC6, MCM3, ORC1 and ORC2 proteins; of these, the post-replicative complex in S phase contains only ORC2; in M phase none of them are bound. The precise nucleotide of binding was identified for the two ORC and the CDC6 proteins near the start sites for leading-strand synthesis; the transition from the pre- to the post-replicative complex is accompanied by a 17 bp displacement of the ORC2 protein towards the start site.

Abdurashidova, Gulnara; Danailov, Miltcho B.; Ochem, Alexander; Triolo, Gianluca; Djeliova, Vera; Radulescu, Sorina; Vindigni, Alessandro; Riva, Silvano; Falaschi, Arturo

2003-01-01

181

Cortical dynamics of human scalp EEG origins in a visually guided motor execution.  

PubMed

The EEG mu rhythm is often used as an index of activation in the sensorimotor cortex. However, the blur caused by volume conduction makes it difficult to identify the exact origin of the EEG rhythm in the brain using only the human scalp EEG. In this study, simultaneous fMRI and EEG measurements were performed during a visually guided motor execution task in order to investigate whether the mu rhythm in the scalp EEG is an indication of the activity in the sensorimotor cortex. In addition, a new method was proposed for reconstruction of the cortical EEG activity through the fusion of fMRI and EEG data. A suppression of mu rhythm appeared around the lateral central electrode sites, just above the sensorimotor cortex, in association with the activity in that region. During a visually guided motor execution task, the alpha rhythms at the occipital electrode sites and the alpha rhythm at the central electrode sites also showed a correlation with the fMRI signal in the occipital and the supplementary motor cortices, respectively. This method allows the investigation of the scalp EEG origin with the spatial precision of fMRI, while retaining dynamic properties of the cortex with the temporal precision of EEG. PMID:22659479

Mizuhara, Hiroaki

2012-09-01

182

Polyacrylamide Gel Identification of Bacterial L-Forms and Mycoplasma Species of Human Origin  

PubMed Central

Polyacrylamide gel electrophoretic patterns of acidified phenol extracts prepared from whole cells can be used for the identification of bacterial L-forms and Mycoplasma species of human origin. Ten human Mycoplasma serotypes and eight L-forms belonging to five different genera were studied. The gel patterns were sufficiently distinct and reproducible that it was possible not only to identify L-forms at the genus level (group with streptococci) and different Mycoplasma serotypes but also to differentiate between the two of them. The parentage of L-forms of Streptobacillus moniliformis L1, Listeria monocytogenes, Streptococcus MG, and Staphylococcus aureus Smith strain was established by relating their gel patterns directly to parent bacteria. It was found that an L-form designated S. moniliformis An (ATCC 14220) was actually an L-form of Proteus. In addition, it was shown electrophoretically that no relationship existed between the Streptococcus MG L-form and M. pneumoniae. The applicability of this method as a diagnostic and taxonomic tool for the differentiation of L-forms and mycoplasmas is discussed. Images

Theodore, Theodore S.; Tully, Joseph G.; Cole, Roger M.

1971-01-01

183

A Single-Nucleotide Polymorphism of Human Neuropeptide S Gene Originated from Europe Shows Decreased Bioactivity  

PubMed Central

Using accumulating SNP (Single-Nucleotide Polymorphism) data, we performed a genome-wide search for polypeptide hormone ligands showing changes in the mature regions to elucidate genotype/phenotype diversity among various human populations. Neuropeptide S (NPS), a brain peptide hormone highly conserved in vertebrates, has diverse physiological effects on anxiety, fear, hyperactivity, food intake, and sleeping time through its cognate receptor-NPSR. Here, we report a SNP rs4751440 (L6-NPS) causing non-synonymous substitution on the 6th position (V to L) of the NPS mature peptide region. L6-NPS has a higher allele frequency in Europeans than other populations and probably originated from European ancestors ?25,000 yrs ago based on haplotype analysis and Approximate Bayesian Computation. Functional analyses indicate that L6-NPS exhibits a significant lower bioactivity than the wild type NPS, with ?20-fold higher EC50 values in the stimulation of NPSR. Additional evolutionary and mutagenesis studies further demonstrate the importance of the valine residue in the 6th position for NPS functions. Given the known physiological roles of NPS receptor in inflammatory bowel diseases, asthma pathogenesis, macrophage immune responses, and brain functions, our study provides the basis to elucidate NPS evolution and signaling diversity among human populations.

Hsueh, Aaron J. W.

2013-01-01

184

Human Herpes Viruses Are Associated with Classic Fever of Unknown Origin (FUO) in Beijing Patients  

PubMed Central

Background Few reports have examined the viral aetiology of fever of unknown origin (FUO). Objective This study determined the prevalence of human herpes virus (HHV) DNA in blood of Chinese patients with classic FUO using the polymerase chain reaction (PCR) and explored the possible role of HHV. Study design Blood samples were collected from 186 patients (151 children, 35 adults) with classic FUO and 143 normal individuals in Beijing during the years 2009–2012. The HHV DNA, including Herpes simplex virus (HSV)-1/2, Varicella zoster virus (VZV), Cytomegalovirus (CMV), Epstein–Barr virus (EBV), and Human herpes virus (HHV)-6 and -7, was detected by multiplex PCR. The epidemiological and clinical features were also analysed. Results HHV DNA was detected in 63 (33.9%) of the FUO patients, and the prevalence of EBV and HHV-6 was significantly higher than in the normal cohort. HHV co-infection was also frequent (10.2%) in the patients with FUO. The majority of patients with HHV infection present with a fever only. Our data also revealed that EBV infection was associated with hepatitis and abnormal blood indices, HHV-6 was associated with a cough, and HHV-7 was associated with hepatitis. Conclusions HHVs are associated with Chinese patients (especially for children) with classic FUO. Our study adds perspective to the aetiological and clinical characteristics of classic FUO in beijing patients.

Zhou, Weimin; Tan, Xinyi; Li, Yamin; Tan, Wenjie

2014-01-01

185

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

PubMed Central

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.

Moya-Sola, Salvador; Alba, David M.; Almecija, Sergio; Casanovas-Vilar, Isaac; Kohler, Meike; De Esteban-Trivigno, Soledad; Robles, Josep M.; Galindo, Jordi; Fortuny, Josep

2009-01-01

186

Assembly of the Human Origin Recognition Complex Occurs through Independent Nuclear Localization of Its Components*  

PubMed Central

Initiation of eukaryotic genome duplication begins when a six-subunit origin recognition complex (ORC) binds to DNA. However, the mechanism by which this occurs in vivo and the roles played by individual subunits appear to differ significantly among organisms. Previous studies identified a soluble human ORC(2–5) complex in the nucleus, an ORC(1–5) complex bound to chromatin, and an Orc6 protein that binds weakly, if at all, to other ORC subunits. Here we show that stable ORC(1–6) complexes also can be purified from human cell extracts and that Orc6 and Orc1 each contain a single nuclear localization signal that is essential for nuclear localization but not for ORC assembly. The Orc6 nuclear localization signal, which is essential for Orc6 function, is facilitated by phosphorylation at its cyclin-dependent kinase consensus site and by association with Kpna6/1, nuclear transport proteins that did not co-purify with other ORC subunits. These and other results support a model in which Orc6, Orc1, and ORC(2–5) are transported independently to the nucleus where they can either assemble into ORC(1–6) or function individually.

Ghosh, Soma; Vassilev, Alex P.; Zhang, Junmei; Zhao, Yingming; DePamphilis, Melvin L.

2011-01-01

187

Re-evaluation of in vitro radiosensitivity of human fibroblasts of different genetic origins.  

PubMed

A statistical analysis of the radiosensitivity of 204 different survival curves of nontransformed human fibroblast cell strains of different genetic origins was made using three criteria: the multi-target one-hit model (characterized by parameters n and D0), the surviving fraction for a 2 Gy dose (S2) and the mean inactivation dose (D). D is found to be the best parameter for characterization of anomalous radiosensitivity linked to a genetic disorder and for discrimination between groups of cell strains of differing radiosensitivity. Its use allows the description of a range of 'normal' radiosensitivity for control fibroblasts and the classification of the various genetic disorders as a function of their mean radiosensitivity expressed in terms of D. Nine groups of cell strains appear to exhibit radiosensitivity which differs significantly from that of the controls: seven groups are hypersensitive (ataxia-telangiectasia homozygotes and heterozygotes, Cockayne's syndrome, Gardner's syndrome, 5-oxoprolinuria homozygotes and heterozygotes, Fanconi's anaemia) and two groups are more radioresistant (fibroblasts from retinoblastoma patients and from individuals with chromosome 13 anomalies). Since the coupled parameter n and D0 failed to discriminate between the radiosensitivity of the different genetic groups, we recommend the use of D to make an intercomparison of intrinsic radiosensitivity of nontransformed human fibroblasts. PMID:3488286

Deschavanne, P J; Debieu, D; Fertil, B; Malaise, E P

1986-08-01

188

Excitation-emission matrices measurements of human cutaneous lesions: tool for fluorescence origin  

NASA Astrophysics Data System (ADS)

The light induced fluorescence (LIF) technique has the potential of providing real-time diagnosis of malignant and premalignant skin tissue; however, human skin is a multilayered and inhomogeneous organ with different optical properties that complicate the analysis of cutaneous fluorescence spectra. In spite of the difficulties related to the detection and analysis of fluorescent data from skin lesions, this technique is among the most widely applied techniques in laboratorial and pre-clinical investigations for early skin neoplasia diagnosis. The important point is to evaluate all sources of intrinsic fluorescence and find any significant alterations distinguishing the normal skin from a cancerous state of the tissue; this would make the autofluorescence signal obtained useful for the development of a non-invasive diagnostic tool for the dermatological practice. Our investigations presented here were based on ex vivo point-by-point measurements of excitation-emission matrices (EEM) from excised tumor lesions and the surrounding skin taken during the daily clinical practice of Queen Jiovanna- ISUL University Hospital, Sofia, the local Ethical Committee's approval having already been obtained. The fluorescence emission was measured between 300 nm and 800 nm using excitation in the 280-440 nm spectral range. In the process of excitation-emission matrices (EEM) measurements we could establish the origin of the autofluorescence and the compounds related by assigning the excitation and emission maxima obtained during the experiments. The EEM were compared for normal human skin, basal cell carcinoma, squamous cell carcinoma, benign nevi and malignant melanoma lesions to obtain information for the most common skin malignancies and their precursors. The main spectral features and the applicability of the technique of autofluorescent spectroscopy of human skin in general as an initial diagnostic tool are discussed as well.

Zhelyazkova, A.; Borisova, E.; Angelova, L.; Pavlova, E.; Keremedchiev, M.

2013-11-01

189

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  

Microsoft Academic Search

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,

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

2009-01-01

190

Human cranial diversity and evidence for an ancient lineage of modern humans  

Microsoft Academic Search

This study examines the genetic affinities of various modern human groupings using a multivariate analysis of morphometric data. Phylogenetic relationships among these groupings are also explored using neighbor-joining analysis of the metric data. Results indicate that the terminal Pleistocene\\/early Holocene fossils from Australasia exhibit a close genetic affinity with early modern humans from the Levant. Furthermore, recent human populations and

Michael A. Schillaci

2008-01-01

191

An early and enduring advanced technology originating 71,000 years ago in South Africa.  

PubMed

There is consensus that the modern human lineage appeared in Africa before 100,000 years ago. But there is debate as to when cultural and cognitive characteristics typical of modern humans first appeared, and the role that these had in the expansion of modern humans out of Africa. Scientists rely on symbolically specific proxies, such as artistic expression, to document the origins of complex cognition. Advanced technologies with elaborate chains of production are also proxies, as these often demand high-fidelity transmission and thus language. Some argue that advanced technologies in Africa appear and disappear and thus do not indicate complex cognition exclusive to early modern humans in Africa. The origins of composite tools and advanced projectile weapons figure prominently in modern human evolution research, and the latter have been argued to have been in the exclusive possession of modern humans. Here we describe a previously unrecognized advanced stone tool technology from Pinnacle Point Site 5-6 on the south coast of South Africa, originating approximately 71,000 years ago. This technology is dominated by the production of small bladelets (microliths) primarily from heat-treated stone. There is agreement that microlithic technology was used to create composite tool components as part of advanced projectile weapons. Microliths were common worldwide by the mid-Holocene epoch, but have a patchy pattern of first appearance that is rarely earlier than 40,000 years ago, and were thought to appear briefly between 65,000 and 60,000 years ago in South Africa and then disappear. Our research extends this record to ~71,000 years, shows that microlithic technology originated early in South Africa, evolved over a vast time span (~11,000 years), and was typically coupled to complex heat treatment that persisted for nearly 100,000 years. Advanced technologies in Africa were early and enduring; a small sample of excavated sites in Africa is the best explanation for any perceived 'flickering' pattern. PMID:23135405

Brown, Kyle S; Marean, Curtis W; Jacobs, Zenobia; Schoville, Benjamin J; Oestmo, Simen; Fisher, Erich C; Bernatchez, Jocelyn; Karkanas, Panagiotis; Matthews, Thalassa

2012-11-22

192

Recognition of nonpeptide antigens by human V?9V?2 T cells requires contact with cells of human origin  

PubMed Central

It is becoming apparent that ?? T cells form an important part of the adaptive immune response. However, the ligands recognized by ?? T cell receptors (TCRs) and the exact biological function of the cells that express this receptor remain unclear. Numerous studies have shown that the dominant human peripheral blood subset of ?? T cells, which express a V?9V?2 TCR, can activate in response to low molecular weight nonpeptidic molecules. Some of these components have been purified from bacteria or parasites. We examined the activation of polyclonal ?? T cell lines, clones with V?9V?2 and V?9V?1 TCRs, and ?? T cells directly ex vivo in response to multiple phosphate, alkylamine and aminobisphosphonate (nBP) antigens and purified protein derivative from Mycobacterium tuberculosis (PPD). V?9V?2 T cells were able to respond to multiple small organic molecules of highly variable structure whereas cells expressing a similar V?9 chain paired with a V?1 chain failed to recognize these antigens. Thus, the TCR ? chain appears to make an important contribution to the recognition of these antigens. The kinetics of responses to alkylphosphate and alkylamine antigens differ from those of responses to the nBP pamidronate. These different classes of antigen are believed to have differed mechanisms of action. Such differences explain why nBPs can be pulsed onto antigen presenting cells (APCs) and still retain their ability to activate ?? T cells while alkylphosphate and alkylamine antigens cannot. We also demonstrate that a substantial proportion of the cells that produce IFN? directly ex vivo in response to PPD are ?? T cells and that ?? T cell activation requires contact with cells of human origin.

GREEN, A E; LISSINA, A; HUTCHINSON, S L; HEWITT, R E; TEMPLE, B; JAMES, D; BOULTER, J M; PRICE, D A; SEWELL, A K

2004-01-01

193

A Novel Family of Human Leukocyte Antigen Class II Receptors May Have Its Origin in Archaic Human Species*  

PubMed Central

HLA class II ? and ? chains form receptors for antigen presentation to CD4+ T cells. Numerous pairings of class II ? and ? subunits from the wide range of haplotypes and isotypes may form, but most of these combinations, in particular those produced by isotype mixing, yielded mismatched dimers. It is unclear how selection of functional receptors is achieved. At the atomic level, it is not known which interactions of class II residues regulate selection of matched ?? heterodimers and the evolutionary origin of matched isotype mixed dimer formation. In this study we investigated assembly of isotype-mixed HLA class II ? and ? heterodimers. Assembly and carbohydrate maturation of various HLA-class II isotype-mixed ? and ? subunits was dependent on the groove binding section of the invariant chain (Ii). By mutation of polymorphic DP? sequences, we identified two motifs, Lys-69 and GGPM-(84–87), that are engaged in Ii-dependent assembly of DP? with DR?. We identified five members of a family of DP? chains containing Lys-69 and GGPM 84–87, which assemble with DR?. The Lys/GGPM motif is present in the DP? sequence of the Neanderthal genome, and this ancient sequence is related to the human allele DPB1*0401. By site-directed mutagenesis, we inspected Neanderthal amino acid residues that differ from the DPB1*0401 allele and aimed to determine whether matched heterodimers are formed by assembly of DP? mutants with DR?. Because the *0401 allele is rare in the sub-Saharan population but frequent in the European population, it may have arisen in modern humans by admixture with Neanderthals in Europe.

Temme, Sebastian; Zacharias, Martin; Neumann, Jurgen; Wohlfromm, Sebastian; Konig, Angelika; Temme, Nadine; Springer, Sebastian; Trowsdale, John; Koch, Norbert

2014-01-01

194

Microchip electrophoresis of Alu elements for gender determination and inference of human ethnic origin.  

PubMed

We performed a series of multi-locus PCRs followed by the rapid and efficient microchip electrophoretic sorting of Alu products with LIF detection. Five polymorphic human-specific Alu insertions (RC5, A1, PV92, TPA and ACE) were used for inference of human ethnicity and two monomorphic Alu insertions for sex typing, one fixed on the X chromosome (AluSTXa) and the other on the Y chromosome (AluSTYa). These markers were used to generate unique DNA profiles for five different DNA samples. The PCR-based assays used primers that flank the insertion point to determine genotypes based on the presence or absence of the Alu element. A1, RC5, PV92, TPA and ACE were used for ethnicity determinations and have two alleles, each indicating the presence (+) or absence (-) of the Alu element on the paired chromosomes, which results in three genotypes (+/+, +/- or -/-). RC5 and A1 did not show ethnic heterogeneity resulting in a homozygous (-/-) genotype, which correctly inferred that DNA samples originating from a Caucasian male and an Asian male were not of African ancestry. The results from the five Alu markers indicated that these Alu loci could assist in identifying the individual's ethnicity using microchip electrophoresis in under 15 min of separation time. Using microchip electrophoresis and mixed genotype ratios, male DNA-to-female DNA of 1:9, corresponding to a ratio of Y-to-X chromosomes of 1:19, was also detected for both AluSTXa and AluSTYa to provide gender identification without requiring separation of female from male cells prior to the assay. PMID:20309932

Njoroge, Samuel K; Witek, Ma?gorzata A; Hupert, Mateusz L; Soper, Steven A

2010-03-01

195

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

PubMed

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

Gavrilets, Sergey

2012-06-19

196

Human origins and the transition from promiscuity to pair-bonding  

PubMed Central

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.

Gavrilets, Sergey

2012-01-01

197

Modification of mipafox-induced inhibition of neuropathy target esterase in neuroblastoma cells of human origin.  

PubMed

A neuroblastoma cell line of human origin was used as an in vitro model system to examine early effects on inhibition of neuropathy target esterase (NTE, also known as neurotoxic esterase) in the presence of agents belonging to classes of chemicals previously demonstrated to modify organophosphorus-induced delayed neuropathy in hens. For this study, differentiated SY-5Y cells were treated for up to 10 min with mipafox, an organophosphorus compound, and NTE inhibition was determined when cells exposed to mipafox were also exposed to the carbamate, aldicarb, and to the calcium channel blocker, verapamil. Cells were exposed to aldicarb or verapamil 5 min before, at the same time, or 2 min after mipafox. Less NTE inhibition was observed when either aldicarb or verapamil was included in the incubation of SY-5Y cells with mipafox. Effects of aldicarb and verapamil on NTE inhibition in differentiated SY-5Y cells were similar to effects in chicken brain homogenates. These results indicate that NTE inhibition can be detected in neuroblastoma cells, that these cells respond in a manner similar to chicken brain, and that mipafox-induced inhibition of NTE can be decreased in the presence of aldicarb or verapamil. PMID:8337699

Nostrandt, A C; Ehrich, M

1993-07-01

198

A human origin type II strain of Toxoplasma gondii causing severe encephalitis in mice.  

PubMed

Despite its capacity for sexual reproduction and global distribution, Toxoplasma gondii has a highly clonal structure, with the majority of isolates belonging to three distinct clonal types. Congenital toxoplasmosis has been associated with type I and type II strains. We here present the first characterization of a T. gondii strain (BGD1) from South-East Europe, isolated from the umbilical blood of a 24-week-old fetus in Serbia. Genotyping, performed by PCR-RFLP using a set of nested PCR markers (5'SAG2, 3'SAG2, BTUB, SAG3, and GRA6), showed that the BGD1 strain possessed a type II genotype. The cytokine patterns in Swiss-Webster mice inoculated with brain cysts of BGD1 and the prototype type II ME49 strain were similar until 180 days post-infection, with highly elevated IFN-gamma, IL-12 and IL-10 by d7 and decreasing thereafter. While both strains induced pneumonia and hepatitis in acute infection (d14), chronic infection (d56) was characterized, in addition to hepatitis, by severe meningoencephalitis, associated with numerous brain cysts. Thus, the BGD1 strain of T. gondii has type II genotypic and immunologic characteristics, but unlike other type II strains of human origin, induces severe encephalitis, making it an alternative to the sheep-derived ME49 strain for experimental models of infection. PMID:16797199

Djurkovi?-Djakovi?, Olgica; Klun, Ivana; Khan, Asis; Nikoli?, Aleksandra; Knezevi?-Usaj, Slavica; Bobi?, Branko; Sibley, L David

2006-07-01

199

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

PubMed Central

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.

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

2013-01-01

200

An Epistemological Approach to French Syllabi on Human Origins during the 19th and 20th Centuries  

ERIC Educational Resources Information Center

This study focuses on how human origins were taught in the French Natural Sciences syllabuses of the 19th and 20th centuries. We evaluate the interval between the publication of scientific concepts and their emergence in syllabuses, i.e., didactic transposition delay (DTD), to determine how long it took for scientific findings pertaining to our…

Quessada, Marie-Pierre; Clement, Pierre

2007-01-01

201

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

PubMed

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

Chaplin, Joyce E

2012-01-01

202

Human origin recognition complex binds preferentially to G-quadruplex-preferable RNA and single-stranded DNA.  

PubMed

Origin recognition complex (ORC), consisting of six subunits ORC1-6, is known to bind to replication origins and function in the initiation of DNA replication in eukaryotic cells. In contrast to the fact that Saccharomyces cerevisiae ORC recognizes the replication origin in a sequence-specific manner, metazoan ORC has not exhibited strict sequence-specificity for DNA binding. Here we report that human ORC binds preferentially to G-quadruplex (G4)-preferable G-rich RNA or single-stranded DNA (ssDNA). We mapped the G-rich RNA-binding domain in the ORC1 subunit, in a region adjacent to its ATPase domain. This domain itself has an ability to preferentially recognize G4-preferable sequences of ssDNA. Furthermore, we found, by structure modeling, that the G-rich RNA-binding domain is similar to the N-terminal portion of AdoMet_MTase domain of mammalian DNA methyltransferase 1. Therefore, in contrast with the binding to double-stranded DNA, human ORC has an apparent sequence preference with respect to its RNA/ssDNA binding. Interestingly, this specificity coincides with the common signature present in most of the human replication origins. We expect that our findings provide new insights into the regulations of function and chromatin binding of metazoan ORCs. PMID:24003239

Hoshina, Shoko; Yura, Kei; Teranishi, Honami; Kiyasu, Noriko; Tominaga, Ayumi; Kadoma, Haruka; Nakatsuka, Ayaka; Kunichika, Tomoko; Obuse, Chikashi; Waga, Shou

2013-10-18

203

Draft Genome Sequence of Lactobacillus fermentum Lf1, an Indian Isolate of Human Gut Origin  

PubMed Central

Lactobacillus fermentum is a normal inhabitant of the human gastrointestinal tract. Here, we report the draft genome sequence of an Indian isolate of the probiotic strain L. fermentum Lf1, isolated from the human gut.

Sharma, Vineet K.; Mallapa, Rashmi H.; Batish, Virender K.

2013-01-01

204

Enterococcus faecalis of human and poultry origin share virulence genes supporting the zoonotic potential of E. faecalis.  

PubMed

Enterococcus faecalis is a major cause of nosocomial infections in humans and has been linked to severe extra-intestinal infections in poultry. A zoonotic potential has been suggested and the aim of the present study was to investigate similarities in virulence gene profiles of E. faecalis originating from infections in humans and poultry respectively. A total of 106 isolates of E. faecalis [26 human clinical isolates, 60 poultry clinical isolates (including two small-colony variants (SCVs) and 20 poultry cloacal isolates] were investigated for presence of seven virulence-associated genes: ace, asa1, cylA, efaA, EF0591, esp and gelE. For each gene, the PCR-amplification product was sequenced from one isolate in each group to explore intragenic variations between genes of human and poultry origin. Haemolytic and protease activities were assessed and isolates were assigned a sequence type (ST). Three of the seven genes investigated (ace, efaA and gelE) were present in all isolates. The asa1 was detected in 63/80 and 13/26 isolates of poultry and human origin respectively. For cylA, the numbers were 46/80 and 14/26 respectively. Among poultry isolates, esp and EF0591 were the least frequently observed genes (1/80 and 20/80 respectively); the prevalences among human isolates were 1/26 and 18/26 respectively. A high degree of similarity between genes in human and poultry isolates were confirmed by sequencing of amplification products. None of the cylA-positive isolates demonstrated haemolytic activity, while the phenotypic expression of gelatinase varied. The ST16 was the only ST shared by human and poultry isolates. The SCV isolates did not show a unique virulence profile or phylogeny. In conclusion, regardless of the distinct phylogenetic background of most E. faecalis isolates of human and poultry origin, we found major similarities in virulence gene profile and gene sequences in isolates from the two sources, supporting the zoonotic risk associated with this organism. PMID:22122842

Olsen, R H; Schønheyder, H C; Christensen, H; Bisgaard, M

2012-06-01

205

Relationship Between Human Physiological Parameters And Geomagnetic Variations Of Solar Origin  

NASA Astrophysics Data System (ADS)

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.

Dimitrova, S.

206

Evidence for sequential and increasing activation of replication origins along replication timing gradients in the human genome.  

PubMed

Genome-wide replication timing studies have suggested that mammalian chromosomes consist of megabase-scale domains of coordinated origin firing separated by large originless transition regions. Here, we report a quantitative genome-wide analysis of DNA replication kinetics in several human cell types that contradicts this view. DNA combing in HeLa cells sorted into four temporal compartments of S phase shows that replication origins are spaced at 40 kb intervals and fire as small clusters whose synchrony increases during S phase and that replication fork velocity (mean 0.7 kb/min, maximum 2.0 kb/min) remains constant and narrowly distributed through S phase. However, multi-scale analysis of a genome-wide replication timing profile shows a broad distribution of replication timing gradients with practically no regions larger than 100 kb replicating at less than 2 kb/min. Therefore, HeLa cells lack large regions of unidirectional fork progression. Temporal transition regions are replicated by sequential activation of origins at a rate that increases during S phase and replication timing gradients are set by the delay and the spacing between successive origin firings rather than by the velocity of single forks. Activation of internal origins in a specific temporal transition region is directly demonstrated by DNA combing of the IGH locus in HeLa cells. Analysis of published origin maps in HeLa cells and published replication timing and DNA combing data in several other cell types corroborate these findings, with the interesting exception of embryonic stem cells where regions of unidirectional fork progression seem more abundant. These results can be explained if origins fire independently of each other but under the control of long-range chromatin structure, or if replication forks progressing from early origins stimulate initiation in nearby unreplicated DNA. These findings shed a new light on the replication timing program of mammalian genomes and provide a general model for their replication kinetics. PMID:22219720

Guilbaud, Guillaume; Rappailles, Aurélien; Baker, Antoine; Chen, Chun-Long; Arneodo, Alain; Goldar, Arach; d'Aubenton-Carafa, Yves; Thermes, Claude; Audit, Benjamin; Hyrien, Olivier

2011-12-01

207

Cytology and time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon  

Microsoft Academic Search

Summary The fine structure, synaptic relationships, distribution and time of origin of interstitial neurons situated within the white matter subjacent to the visual, somatosensory and motor cortices were studied in the human and monkey telencephalon. The analysis was carried out on Nissl-stained serial sections, rapid Golgi impregnations, by acetylcholinesterase (AChE) histochemistry, electron microscopy and [3H]thymidine ([3H]TdR) autoradiography. Interstitial neurons have

Ivica Kostovic; Pasko Rakic

1980-01-01

208

Early Origin for Human-Like Precision Grasping: A Comparative Study of Pollical Distal Phalanges in Fossil Hominins  

PubMed Central

Background The morphology of human pollical distal phalanges (PDP) closely reflects the adaptation of human hands for refined precision grip with pad-to-pad contact. The presence of these precision grip-related traits in the PDP of fossil hominins has been related to human-like hand proportions (i.e. short hands with a long thumb) enabling the thumb and finger pads to contact. Although this has been traditionally linked to the appearance of stone tool-making, the alternative hypothesis of an earlier origin—related to the freeing of the hands thanks to the advent of terrestrial bipedalism—is also possible given the human-like intrinsic hand proportion found in australopiths. Methodology/Principal Findings We perform morphofunctional and morphometric (bivariate and multivariate) analyses of most available hominin pollical distal phalanges, including Orrorin, Australopithecus, Paranthropous and fossil Homo, in order to investigate their morphological affinities. Our results indicate that the thumb morphology of the early biped Orrorin is more human-like than that of australopiths, in spite of its ancient chronology (ca. 6 Ma). Moreover, Orrorin already displays typical human-like features related to precision grasping. Conclusions These results reinforce previous hypotheses relating the origin of refined manipulation of natural objects–not stone tool-making–with the relaxation of locomotor selection pressures on the forelimbs. This suggests that human hand length proportions are largely plesiomorphic, in the sense that they more closely resemble the relatively short-handed Miocene apes than the elongated hand pattern of extant hominoids. With the advent of terrestrial bipedalism, these hand proportions may have been co-opted by early hominins for enhanced manipulative capabilities that, in turn, would have been later co-opted for stone tool-making in the genus Homo, more encephalized than the previous australopiths. This hypothesis remains may be further tested by the finding of more complete hands of unequivocally biped early hominins.

Almecija, Sergio; Moya-Sola, Salvador; Alba, David M.

2010-01-01

209

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...

210

Differential Expression of Matrix Metalloproteases in Human Fibroblasts with Different Origins  

PubMed Central

Fibroblasts are widely distributed cells and are responsible for the deposition of extracellular matrix (ECM) components but also secrete ECM-degrading matrix metalloproteases. A finely balanced equilibrium between deposition and degradation of ECM is essential for structural integrity of tissues. In the past, fibroblasts have typically been understood as a uniform cell population with comparable functions regardless of their origin. Here, we determined growth curves of fibroblasts derived from heart, skin, and lung and clearly show the lowest proliferation rate for cardiac fibroblasts. Furthermore, we examined basal expression levels of collagen and different MMPs in these three types of fibroblasts and compared these concerning their site of origin. Interestingly, we found major differences in basal mRNA expression especially for MMP1 and MMP3. Moreover, we treated fibroblasts with TNF-? and observed different alterations under these proinflammatory conditions. In conclusion, fibroblasts show different properties in proliferation and MMP expression regarding their originated tissue.

Lindner, Diana; Zietsch, Christin; Becher, P. Moritz; Schulze, Karsten; Schultheiss, Heinz-Peter; Tschope, Carsten; Westermann, Dirk

2012-01-01

211

Differential expression of matrix metalloproteases in human fibroblasts with different origins.  

PubMed

Fibroblasts are widely distributed cells and are responsible for the deposition of extracellular matrix (ECM) components but also secrete ECM-degrading matrix metalloproteases. A finely balanced equilibrium between deposition and degradation of ECM is essential for structural integrity of tissues. In the past, fibroblasts have typically been understood as a uniform cell population with comparable functions regardless of their origin. Here, we determined growth curves of fibroblasts derived from heart, skin, and lung and clearly show the lowest proliferation rate for cardiac fibroblasts. Furthermore, we examined basal expression levels of collagen and different MMPs in these three types of fibroblasts and compared these concerning their site of origin. Interestingly, we found major differences in basal mRNA expression especially for MMP1 and MMP3. Moreover, we treated fibroblasts with TNF-? and observed different alterations under these proinflammatory conditions. In conclusion, fibroblasts show different properties in proliferation and MMP expression regarding their originated tissue. PMID:22500233

Lindner, Diana; Zietsch, Christin; Becher, P Moritz; Schulze, Karsten; Schultheiss, Heinz-Peter; Tschöpe, Carsten; Westermann, Dirk

2012-01-01

212

Cumulative impacts of human activities on urban garden soils: origin and accumulation of metals.  

PubMed

The concentration of heavy metals and soil properties in fifty urban garden soils of Szeged (SE Hungary) were determined to evaluate the cumulative impacts of urbanization and cultivation on these soils. Using two enrichment factors (EFs) (based on reference horizon; Ti as reference element) and multivariate statistical analysis (PCA), the origin of the studied elements was defined. According to statistical coincidence of EFs confirmed by t-test, anthropogenic enrichment of Cu (EF = 4), Zn (EF = 2.7) and Pb (EF = 2.5) was significant in topsoils. Moreover, PCA also revealed the geogenic origin of Ni, Co, Cr and As and differentiated two groups of the anthropogenic metals [Pb, Zn] [Cu]. Spatial distribution of the metals visualized by GIS reflected the traffic origin of Pb; while based on ANOVA, the anthropogenic source of Cu is relevant (mainly pesticides) and there is a statistically significant difference in its concentration depending on land use. PMID:23500047

Szolnoki, Zs; Farsang, A; Puskás, I

2013-06-01

213

Complex origins of breadfruit (Artocarpus altilis, Moraceae): implications for human migrations in Oceania  

Microsoft Academic Search

Breadfruit (Artocarpus altilis, Moraceae), a traditional starch crop in Oceania, has enjoyed legendary status ever since its role in the infamous mutiny aboard the H.M.S. Bounty in 1789, yet its origins remain unclear. Breadfruit's closest relatives are A. camansi and A. mariannensis. DNA fingerprinting data (AFLP, amplified fragment length polymorphisms) from over 200 breadfruit cultivars, 30 A. camansi, and 24

NYREE J. C. ZEREGA; DIANE RAGONE; TIMOTHY J. MOTLEY

2004-01-01

214

Biofilm formation by Mycobacterium avium isolates originating from humans, swine and birds  

Microsoft Academic Search

BACKGROUND: Mycobacterium avium includes the subspecies avium, silvaticum, paratuberculosis and hominissuis, and M. avium subspecies has been isolated from various environments all over the world including from biofilms in water distribution systems. The aim of this study was to examine isolates of M. avium subsp. avium and M. avium subsp. hominissuis of different origin for biofilm formation and to look

Tone Bjordal Johansen; Angelika Agdestein; Ingrid Olsen; Sigrun Fredsvold Nilsen; Gudmund Holstad; Berit Djønne

2009-01-01

215

Archaic human genomics.  

PubMed

For much of the 20th century, the predominant view of human evolutionary history was derived from the fossil record. Homo erectus was seen arising in Africa from an earlier member of the genus and then spreading throughout the Old World and into the Oceania. A regional continuity model of anagenetic change from H. erectus via various intermediate archaic species into the modern humans in each of the regions inhabited by H. erectus was labeled the multiregional model of human evolution (MRE). A contrasting model positing a single origin, in Africa, of anatomically modern H. sapiens with some populations later migrating out of Africa and replacing the local archaic populations throughout the world with complete replacement became known as the recent African origin (RAO) model. Proponents of both models used different interpretations of the fossil record to bolster their views for decades. In the 1980s, molecular genetic techniques began providing evidence from modern human variation that allowed not only the different models of modern human origins to be tested but also the exploration demographic history and the types of selection that different regions of the genome and even specific traits had undergone. The majority of researchers interpreted these data as strongly supporting the RAO model, especially analyses of mitochondrial DNA (mtDNA). Extrapolating backward from modern patterns of variation and using various calibration points and substitution rates, a consensus arose that saw modern humans evolving from an African population around 200,000 years ago. Much later, around 50,000 years ago, a subset of this population migrated out of Africa replacing Neanderthals in Europe and western Asia as well as archaics in eastern Asia and Oceania. mtDNA sequences from more than two-dozen Neanderthals and early modern humans re-enforced this consensus. In 2010, however, the complete draft genomes of Neanderthals and of heretofore unknown hominins from Siberia, called Denisovans, demonstrated gene flow between these archaic human species and modern Eurasians but not sub-Saharan Africans. Although the levels of gene flow may be very limited, this unexpected finding does not fit well with either the RAO model or MRE model. More thorough sampling of modern human diversity, additional fossil discoveries, and the sequencing of additional hominin fossils are necessary to throw light onto our origins and our history. PMID:23124308

Disotell, Todd R

2012-01-01

216

Structure of the NS1 Protein N-Terminal Origin Recognition/Nickase Domain from the Emerging Human Bocavirus  

PubMed Central

Human bocavirus is a newly identified, globally prevalent, parvovirus that is associated with respiratory infection in infants and young children. Parvoviruses encode a large nonstructural protein 1 (NS1) that is essential for replication of the viral single-stranded DNA genome and DNA packaging and may play versatile roles in virus-host interactions. Here, we report the structure of the human bocavirus NS1 N-terminal domain, the first for any autonomous parvovirus. The structure shows an overall fold that is canonical to the histidine-hydrophobic-histidine superfamily of nucleases, which integrates two distinct DNA-binding sites: (i) a positively charged region mediated by a surface hairpin (residues 190 to 198) that is responsible for recognition of the viral origin of replication of the double-stranded DNA nature and (ii) the nickase active site that binds to the single-stranded DNA substrate for site-specific cleavage. The structure reveals an acidic-residue-rich subdomain that is present in bocavirus NS1 proteins but not in the NS1 orthologs in erythrovirus or dependovirus, which may mediate bocavirus-specific interaction with DNA or potential host factors. These results provide insights into recognition of the origin of replication and nicking of DNA during bocavirus genome replication. Mapping of variable amino acid residues of NS1s from four human bocavirus species onto the structure shows a scattered pattern, but the origin recognition site and the nuclease active site are invariable, suggesting potential targets for antivirals against this clade of highly diverse human viruses.

Tewary, Sunil Kumar; Shen, Weiran; Qiu, Jianming

2013-01-01

217

Identification of DNA of human origin based on amplification of human-specific mitochondrial cytochrome b region  

Microsoft Academic Search

Species-specific differences in a non-polymorphic region of the mitochondrial cytochrome b gene appear to be large enough to allow human-specific amplification of forensic DNA samples. We therefore developed a PCR-based method using newly designed primers to amplify a 157-bp portion of the human mitochondrial cytochrome b gene. The forward and reverse primers were designed to hybridize to regions of the

Hirokazu Matsuda; Yasuhisa Seo; Eiji Kakizaki; Shuji Kozawa; Eri Muraoka; Nobuhiro Yukawa

2005-01-01

218

Bone Marrow Stem Cell Origin of Human Breast Cancer Using Transgenic Mouse Models.  

National Technical Information Service (NTIS)

There is emerging evidence that transformed stem cells may be the source of human cancers. We felt that transgenic mouse models were ideally suited to examine this question and proposed to conduct marrow transplant experiments to test whether marrow stem ...

S. H. Barsky

2008-01-01

219

Origin and evolution of candidate mental retardation genes on the human X chromosome (MRX)  

Microsoft Academic Search

BACKGROUND: The human X chromosome has a biased gene content. One group of genes that is over-represented on the human X are those expressed in the brain, explaining the large number of sex-linked mental retardation (MRX) syndromes. RESULTS: To determine if MRX genes were recruited to the X, or whether their brain-specific functions were acquired after relocation to the mammalian

Margaret L Delbridge; Daniel A McMillan; Ruth J Doherty; Janine E Deakin; Jennifer A Marshall Graves

2008-01-01

220

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

PubMed

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

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

221

Uterine Vasculature Remodeling in Human Pregnancy Involves Functional Macrochimerism by Endothelial Colony Forming Cells of Fetal Origin  

PubMed Central

The potency of adult-derived circulating progenitor endothelial colony forming cells (ECFCs) is drastically surpassed by their fetal counterparts. Human pregnancy is associated with robust intensification of blood flow and vascular expansion in the uterus, crucial for placental perfusion and fetal supply. Here, we investigate whether fetal ECFCs transmigrate to maternal bloodstream and home to locations of maternal vasculogenesis, primarily the pregnant uterus. In the first instance, endothelial-like cells, originating from mouse fetuses expressing paternal eGFP, were identified within uterine endothelia. Subsequently, LacZ or enhanced green fluorescent protein (eGFP)-labeled human fetal ECFCs, transplanted into immunodeficient (NOD/SCID) fetuses on D15.5 pregnancy, showed similar integration into the mouse uterus by term. Mature endothelial controls (human umbilical vein endothelial cells), similarly introduced, were unequivocally absent. In humans, SRY was detected in 6 of 12 myometrial microvessels obtained from women delivering male babies. The copy number was calculated at 175 [IQR 149–471] fetal cells per millimeter square endothelium, constituting 12.5% of maternal vessel lumina. Cross-sections of similar human vessels, hybridized for Y-chromosome, positively identified endothelial-associated fetal cells. It appears that through ECFC donation, fetuses assist maternal uterine vascular expansion in pregnancy, potentiating placental perfusion and consequently their own fetal supply. In addition to fetal growth, this cellular mechanism holds implications for materno-fetal immune interactions and long-term maternal vascular health.

Sipos, Peter I; Rens, Willem; Schlecht, HElene; Fan, Xiaohu; Wareing, Mark; Hayward, Christina; Hubel, Carl A; Bourque, Stephane; Baker, Philip N; Davidge, Sandra T; Sibley, Colin P; Crocker, Ian P

2013-01-01

222

Heterogeneity among Virulence and Antimicrobial Resistance Gene Profiles of Extraintestinal Escherichia coli Isolates of Animal and Human Origin  

PubMed Central

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.

Maynard, Christine; Bekal, Sadjia; Sanschagrin, Francois; Levesque, Roger C.; Brousseau, Roland; Masson, Luke; Lariviere, Serge; Harel, Josee

2004-01-01

223

Induced chirality upon crocetin binding to human serum albumin: origin and nature  

Microsoft Academic Search

Binding to human serum albumin (HSA) of the natural, achiral carotenoid crocetin, having hypocholesterolemic and antitumour effects, was investigated in detail by circular dichroism (CD) and absorption spectroscopy. It has been shown that in the visible absorption region the crocetin–HSA complex exhibits a well-defined induced circular dichroic spectrum with two major bands of opposite sign, proving excitonic interaction between carotenoids

Ferenc Zsila; Zsolt Bikádi; Miklós Simonyi

2001-01-01

224

Improved Analyses of Human mtDNA Sequences Support a Recent African Origin for Homo sapiens  

Microsoft Academic Search

New quantitative methods are applied to the 135 human mitochondrial sequences from the Vigilant et al. data set. General problems in analyzing large numbers of short sequences are discussed, and an improved strategy is suggested. A key feature is to focus not on individual trees but on the general \\

David Penny; Mike Steel; Peter J. Waddell; Michael D. Hendy

1995-01-01

225

Dendritic Cell Ontogeny: A Human Dendritic Cell Lineage of Myeloid Origin  

Microsoft Academic Search

Dendritic cells (DC) have been thought to represent a family of closely related cells with similar functions and developmental pathways. The best-characterized precursors are the epidermal Langerhans cells, which migrate to lymphoid organs and become activated DC in response to inflammatory stimuli. Here, we demonstrate that a large subset of DC in the T cell-dependent areas of human lymphoid organs

Johanna Olweus; Andrew Bitmansour; Roger Warnke; Peter A. Thompson; Jose Carballido; Louis J. Picker; Fridtjof Lund-Johansen

1997-01-01

226

Prenatal Origins of Human Intrapulmonary Arteries Formation and Smooth Muscle Maturation  

Microsoft Academic Search

Recent studies on the morphogenesis of the pulmonary arter- ies have focused on nonhuman species such as the chick and the mouse. Using immunohistochemical techniques, we have studied 16 lungs from human embryos and fetuses from 28 d of gestation to newborn, using serial sections stained with a panel of antibodies specific for endothelium, smooth muscle, and extracellular matrix proteins.

Susan M. Hall; Alison A. Hislop; Christine M. Pierce; Sheila G. Haworth

227

Recently Recovered Kenyapithecus Mandible and Its Implications for Great Ape and Human Origins  

Microsoft Academic Search

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

Monte L. McCrossin; Brenda R. Benefit

1993-01-01

228

At last: classification of human mammary cells elucidates breast cancer origins.  

PubMed

Current breast cancer classification systems are based on molecular evaluation of tumor receptor status and do not account for distinct morphological phenotypes. In other types of cancer, taxonomy based on normal cell phenotypes has been extremely useful for diagnosis and treatment strategies. In this issue of the JCI, Santagata and colleagues developed a breast cancer classification scheme based on characterization of healthy mammary cells. Reclassification of breast cancer cells and breast cancer tissue microarrays with this system correlated with prognosis better than the standard receptor status designation. This scheme provides a major advance toward our understanding of the origin of the cells in the breast and breast cancers. PMID:24463442

Cardiff, Robert D; Borowsky, Alexander D

2014-02-01

229

Circular Epstein-Barr virus genomes of reduced size in a human lymphoid cell line of infectious mononucleosis origin.  

PubMed Central

Circular Epstein-Barr virus (EBV) DNA molecules have been purified and characterized from a human lymphoid cell line derived from a case of heterophile antibody-positive, blood transfusion-induced infectious mononucleosis, 883L. The circular EBV DNA in three cell lines obtained by transformation of human umbilical cord blood leukocytes with a strain of EBV originally derived from 883L was also studied. As estimated from sedimentation velocity data and electron microscopy, the circular EBV DNA molecules are 10 to 15% smaller than either the circular EBV DNA previously found intracellularly in several other types of EBV-transformed cells or the linear EBV DNA present extracellularly in virus particles. In addition, the EBV-transformed cord blood cell lines studied here differed from other EBV-transformed cells in that integrated virus DNA sequences could not be detected. Images

Adams, A; Bjursell, G; Kaschka-Dierich, C; Lindahl, T

1977-01-01

230

Successful experimental infections of a human volunteer and Mongolian gerbils with Giardia of animal origin.  

PubMed

A human volunteer and Mongolian gerbils were shown to be susceptible to infection with Giardia from a Gambian giant pouched rat. The course of infection and the pattern of cyst excretion, as well as the number of cysts in gerbils which were given the same inocula of Giardia, differed from the course of infection in humans. The latent period in gerbils was longer and the gerbils continually excreted numerous cysts, whereas excretion of cysts, in smaller numbers, by the volunteer was intermittent. Moderate clinical symptoms were noted in the volunteer, and the infection was confirmed by the development of anti-Giardia antibodies. The study demonstrated the zoonotic character of giardiasis and has important implications for the epidemiology of Giardia. PMID:7974691

Majewska, A C

1994-01-01

231

An Ancient Evolutionary Origin of Genes Associated with Human Genetic Diseases  

PubMed Central

Several thousand genes in the human genome have been linked to a heritable genetic disease. The majority of these appear to be nonessential genes (i.e., are not embryonically lethal when inactivated), and one could therefore speculate that they are late additions in the evolutionary lineage toward humans. Contrary to this expectation, we find that they are in fact significantly overrepresented among the genes that have emerged during the early evolution of the metazoa. Using a phylostratigraphic approach, we have studied the evolutionary emergence of such genes at 19 phylogenetic levels. The majority of disease genes was already present in the eukaryotic ancestor, and the second largest number has arisen around the time of evolution of multicellularity. Conversely, genes specific to the mammalian lineage are highly underrepresented. Hence, genes involved in genetic diseases are not simply a random subset of all genes in the genome but are biased toward ancient genes.

Domazet-Loso, Tomislav

2008-01-01

232

Origin of the koilocyte in condylomata of the human cervix: ultrastructural study.  

PubMed

Twelve biopsies from condylomatous lesions of the human cervix were examined by transmission electron microscopy in order to study koilocytotic cells. The ultrastructure of koilocytes, revealed mainly cytoplasmic changes in the perinuclear area. These changes first appeared in cells of the intermediate layers and extended to the surface of the epithelium. The cells involved showed small perinuclear areas, with a fine granular material, which appeared as a lysis of the cytoplasmic matrix, forming microvacuolelike structures that gradually enlarged and fused together, ending with the formation of a large clear zone (koliocytosis). Binucleation and polylobulation were constant features. Intranuclear virus particles were often associated with koilocytes. Tubules and large bundles or single filamentous structures were also observed in koilocytes detected in smears and biopsies. This study provides further evidence that the koilocytes is the result of a process characterized by cellular changes due to cytopathogenic effect of the human papillomavirus. PMID:6945004

Casas-Cordero, M; Morin, C; Roy, M; Fortier, M; Meisels, A

1981-01-01

233

Evidence Supporting a Zoonotic Origin of Human Coronavirus Strain NL63  

PubMed Central

The relationship between bats and coronaviruses (CoVs) has received considerable attention since the severe acute respiratory syndrome (SARS)-like CoV was identified in the Chinese horseshoe bat (Rhinolophidae) in 2005. Since then, several bats throughout the world have been shown to shed CoV sequences, and presumably CoVs, in the feces; however, no bat CoVs have been isolated from nature. Moreover, there are very few bat cell lines or reagents available for investigating CoV replication in bat cells or for isolating bat CoVs adapted to specific bat species. Here, we show by molecular clock analysis that alphacoronavirus (?-CoV) sequences derived from the North American tricolored bat (Perimyotis subflavus) are predicted to share common ancestry with human CoV (HCoV)-NL63, with the most recent common ancestor between these viruses occurring approximately 563 to 822 years ago. Further, we developed immortalized bat cell lines from the lungs of this bat species to determine if these cells were capable of supporting infection with HCoVs. While SARS-CoV, mouse-adapted SARS-CoV (MA15), and chimeric SARS-CoVs bearing the spike genes of early human strains replicated inefficiently, HCoV-NL63 replicated for multiple passages in the immortalized lung cells from this bat species. These observations support the hypothesis that human CoVs are capable of establishing zoonotic-reverse zoonotic transmission cycles that may allow some CoVs to readily circulate and exchange genetic material between strains found in bats and other mammals, including humans.

Huynh, Jeremy; Li, Shimena; Yount, Boyd; Smith, Alexander; Sturges, Leslie; Olsen, John C.; Nagel, Juliet; Johnson, Joshua B.; Agnihothram, Sudhakar; Gates, J. Edward; Frieman, Matthew B.; Baric, Ralph S.

2012-01-01

234

Recent African Origin of Modern Humans Revealed by Complete Sequences of Hominoid Mitochondrial DNAs  

Microsoft Academic Search

We analyzed the complete mitochondrial DNA (mtDNA) sequences of three humans (African, European, and Japanese), three African apes (common and pygmy chimpanzees, and gorilla), and one orangutan in an attempt to estimate most accurately the substitution rates and divergence times of hominoid mtDNAs. Nonsynonymous substitutions and substitutions in RNA genes have accumulated with an approximately clock-like regularity. From these substitutions

Satoshi Horai; Kenji Hayasaka; Rumi Kondo; Kazuo Tsugane; Naoyuki Takahata

1995-01-01

235

Stem Cell Origin of Death-from-Cancer Phenotypes of Human Prostate and Breast Cancers  

Microsoft Academic Search

In clinical terms, all human cancers diagnosed in individuals can be divided in two major categories: malignant tumors that\\u000a will be cured with the existing cancer therapies and tumors that have therapy-resistant phenotypes and will return after initial\\u000a treatment as incurable metastatic disease. These tumors manifesting clinically lethal death-from-cancer phenotypes represent\\u000a the most formidable challenge of experimental, translational, and clinical

Gennadi V. Glinsky

2007-01-01

236

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

Microsoft Academic Search

\\u000a Researchers from the cognitive and spatial sciences are studying text descriptions of movement patterns in order to examine\\u000a how humans communicate and understand spatial information. In particular, route directions offer a rich source of information\\u000a on how cognitive systems conceptualize movement patterns by segmenting them into meaningful parts. Route directions are composed\\u000a using a plethora of cognitive spatial organization principles:

Xiao Zhang; Prasenjit Mitra; Alexander Klippel; Alan M. MacEachren

2010-01-01

237

A new Late Miocene great ape from Kenya and its implications for the origins of African great apes and humans  

PubMed Central

Extant African great apes and humans are thought to have diverged from each other in the Late Miocene. However, few hominoid fossils are known from Africa during this period. Here we describe a new genus of great ape (Nakalipithecus nakayamai gen. et sp. nov.) recently discovered from the early Late Miocene of Nakali, Kenya. The new genus resembles Ouranopithecus macedoniensis (9.6–8.7 Ma, Greece) in size and some features but retains less specialized characters, such as less inflated cusps and better-developed cingula on cheek teeth, and it was recovered from a slightly older age (9.9–9.8 Ma). Although the affinity of Ouranopithecus to the extant African apes and humans has often been inferred, the former is known only from southeastern Europe. The discovery of N. nakayamai in East Africa, therefore, provides new evidence on the origins of African great apes and humans. N. nakayamai could be close to the last common ancestor of the extant African apes and humans. In addition, the associated primate fauna from Nakali shows that hominoids and other non-cercopithecoid catarrhines retained higher diversity into the early Late Miocene in East Africa than previously recognized.

Kunimatsu, Yutaka; Nakatsukasa, Masato; Sawada, Yoshihiro; Sakai, Tetsuya; Hyodo, Masayuki; Hyodo, Hironobu; Itaya, Tetsumaru; Nakaya, Hideo; Saegusa, Haruo; Mazurier, Arnaud; Saneyoshi, Mototaka; Tsujikawa, Hiroshi; Yamamoto, Ayumi; Mbua, Emma

2007-01-01

238

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

PubMed Central

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.

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

2013-01-01

239

Studies on the origin of human amniotic fluid cells by immunofluorescent staining of keratin filaments.  

PubMed

Cultivated cells obtained by amniocentesis for antenatal diagnosis were examined for the presence of keratin filaments by immunofluorescent staining techniques. In primary cultures, cells in fibroblast type colonies do not possess keratin filaments whereas cells in epithelial type colonies show positive staining of keratin fibres. The majority of cells in amniotic fluid type colonies also stain positively with antikeratin antibody. After the primary cells have been subcultured, most of them appear fibroblastic yet stain positively with antikeratin antibody. The patterns formed by these stained fibres resemble those seen in primary cultures of amniotic fluid type cells. These results indicate that the amniotic fluid type cells (which predominate in primary cultures) and the majority of cells in subcultures (routinely used for antenatal diagnosis of genetic metabolic disorders) are epithelial in origin. PMID:6185680

Chen, W W

1982-12-01

240

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

PubMed Central

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.

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

241

CD34-negative mesenchymal stem-like cells may act as the cellular origin of human aortic valve calcification.  

PubMed

Although various osteogenic inducers contribute to the calcification of human aortic valve interstitial cells, the cellular origin of calcification remains unclear. We immunohistochemically investigated the cellular origin of valve calcification using enzymatically isolated cells from both calcified and non-calcified human aortic valve specimens. CD73-, 90-, and 105-positive and CD45-negative mesenchymal stem-like cells (MSLCs) were isolated from both types of valve specimens using fluorescence-activated cell sorting. MSLCs were further sorted into CD34-negative and -positive cells. Compared with CD34-positive cells, CD34-negative MSLCs were significantly more sensitive to high inorganic phosphate (3.2 mM), calcifying easily in response. Furthermore, immunohistochemical staining showed that significantly higher numbers (~7-9-fold) of CD34-negative compared with CD34-positive MSLCs were localized in calcified aortic valve specimens obtained from calcified aortic stenosis patients. These results suggest that CD34-negative MSLCs are responsible for calcification of the aortic valve. PMID:24120498

Nomura, Anan; Seya, Kazuhiko; Yu, Zaiqiang; Daitoku, Kazuyuki; Motomura, Shigeru; Murakami, Manabu; Fukuda, Ikuo; Furukawa, Ken-Ichi

2013-11-01

242

Y chromosome evidence of earliest modern human settlement in East Asia and multiple origins of Tibetan and Japanese populations  

PubMed Central

Background The phylogeography of the Y chromosome in Asia previously suggested that modern humans of African origin initially settled in mainland southern East Asia, and about 25,000–30,000 years ago, migrated northward, spreading throughout East Asia. However, the fragmented distribution of one East Asian specific Y chromosome lineage (D-M174), which is found at high frequencies only in Tibet, Japan and the Andaman Islands, is inconsistent with this scenario. Results In this study, we collected more than 5,000 male samples from 73 East Asian populations and reconstructed the phylogeography of the D-M174 lineage. Our results suggest that D-M174 represents an extremely ancient lineage of modern humans in East Asia, and a deep divergence was observed between northern and southern populations. Conclusion We proposed that D-M174 has a southern origin and its northward expansion occurred about 60,000 years ago, predating the northward migration of other major East Asian lineages. The Neolithic expansion of Han culture and the last glacial maximum are likely the key factors leading to the current relic distribution of D-M174 in East Asia. The Tibetan and Japanese populations are the admixture of two ancient populations represented by two major East Asian specific Y chromosome lineages, the O and D haplogroups.

Shi, Hong; Zhong, Hua; Peng, Yi; Dong, Yong-Li; Qi, Xue-Bin; Zhang, Feng; Liu, Lu-Fang; Tan, Si-Jie; Ma, Runlin Z; Xiao, Chun-Jie; Wells, R Spencer; Jin, Li; Su, Bing

2008-01-01

243

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

PubMed Central

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.

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

2006-01-01

244

ON THE ORIGIN OF THE HUMAN TREPONEMATOSES (PINTA, YAWS, ENDEMIC SYPHILIS AND VENEREAL SYPHILIS).  

PubMed

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

HACKETT, C J

1963-01-01

245

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

PubMed Central

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 cm2) 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.

Du, Peng; Cheng, Leo K.; Egbuji, John U.; Lammers, Wim J. E. P.; Windsor, John A.; Pullan, Andrew J.

2010-01-01

246

Independent origin of functional MHC class II genes in humans and New World monkeys.  

PubMed

In previous studies, major histocompatibility complex (MHC) class II DP, DQ, and DR families of genes were characterized in different primate species mostly on the basis of their second exon sequences. Resemblances were found between Old World monkey (OWM) and New World monkey (NWM) genes and were interpreted as being the result of transspecies evolution. Subsequent analysis of intron sequences of catarrhine and platyrrhine DRB genes, however, revealed that the amplifiable genes were not, in fact, orthologous. To test other DRB genes and other families of the class II region Southern blot hybridizations were carried out with tamarin genomic DNA using probes specific for the third exons of the tamarin DQA, DQB, DPB, and DRB genes. The hybridizing bands were extracted from the gel and the third exons of the genes were amplified by PCR, cloned, and sequenced. With two exceptions, all NWM class II genes were found to group separately from the human sequences. Only the sequences of one nonfunctional DQB locus appeared to be more closely related to human genes than to other platyrrhine DQB genes. In the DRB family one gene was found that grouped with sheep and strepsirhine DRB sequences and might represent an old gene lineage. To extend the sequences to the second exon, long PCRs were performed on tamarin genomic DNA. This approach was successful for five of the ten third exon sequences. From these data, we conclude that at least the functional MHC class II genes have expanded independently in catarrhines and platyrrhines. PMID:11165710

Kriener, K; O'hUigin, C; Klein, J

2001-01-01

247

Characterization of human tracheal epithelial cells transformed by an origin-defective simian virus 40.  

PubMed Central

To facilitate understanding of the mechanisms underlying pulmonary diseases, including lung cancer and cystic fibrosis, we have transformed and characterized cultures of human tracheal epithelial cells. Cells were transfected by calcium phosphate precipitation with a plasmid containing a replication-defective simian virus 40 (SV40) genome. Colonies of cells with enhanced growth potential were isolated and analyzed for transformation- and epithelial-specific characteristics. Precrisis cells were observed to express the SV40 large tumor antigen, produce cytokeratins, have microvilli, and form tight junctions. After crisis, cells continued to express the SV40 large tumor antigen as well as epithelial-specific cytokeratins and to display the apical membrane microvilli. Apical membrane Cl channels were opened in postcrisis cells exposed to 50 microM forskolin. These channels showed electrical properties similar to those observed in primary cultures. The postcrisis cells have been in culture for greater than 250 generations and are potentially "immortal." In addition to providing a useful in vitro model for the study of ion transport by human airway epithelial cells, the cells can be used to examine stages of neoplastic progression. Images

Gruenert, D C; Basbaum, C B; Welsh, M J; Li, M; Finkbeiner, W E; Nadel, J A

1988-01-01

248

Cytotoxic evaluation of cubic boron nitride in human origin cultured cells.  

PubMed

The aim of this study was to evaluate the cytotoxicity of cubic boron nitride (cBN), a component of surgical cutting tools. The small quantities of cBN that typically remain on implants as a result of the manufacturing process may act as abrasives, injuring tissues surrounding the implant. To determine how cBN affects cells, we treated human neuroblastoma cells (NB-1) and human articular chondrocytes (nHAC-kn) with different concentrations of cBN powder and assessed cell growth and cell survival using the methyl-thiazol-tetrazolium (MTT) assay and a fluorescence probe assay. We also assessed the effects of tungsten carbide (WC) and cobalt (Co), two common components of joint implants, on cell growth and cell survival. Both cBN and WC moderately inhibited NB-1 and nHAC-kn cell growth. However, cBN and WC did not affect cell survival, even at high concentrations (40 microg/ml). By contrast, Co affected cell survival, inducing cell death in both cell types at increasing concentrations. These results suggest that cBN may be less toxic than WC alloys containing Co. PMID:16890396

Koga, Kenjiro; Kaji, Akira; Hirosaki, Kenichi; Hata, Yukako; Ogura, Tsutomu; Fujishita, Osamu; Shintani, Kazuhiro

2006-12-01

249

The Origin and Evolution of Variable Number Tandem Repeat of CLEC4M Gene in the Global Human Population  

PubMed Central

CLEC4M is a C-type lectin gene serving as cell adhesion receptor and pathogen recognition receptor. It recognizes several pathogens of important public health concern. In particular, a highly polymorphic variable number tandem repeat (VNTR) at the neck-region of CLEC4M had been associated with genetic predisposition to some infectious diseases. To gain insight into the origin and evolution of this VNTR in CLEC4M, we studied 21 Africans, 20 Middle Easterns, 35 Europeans, 38 Asians, 13 Oceania, and 18 Americans (a total of 290 chromosomes) from the (Human Genome Diversity Panel) HGDP-CEPH panel; these samples covered most of alleles of this VNTR locus present in human populations. We identified a limited number of haplotypes among the basic repeat subunits that is 69 base pairs in length. Only 8 haplotypes were found. Their sequence identities were determined in the 290 chromosomes. VNTR alleles of different repeat length (from 4 to 9 repeats) were analyzed for composition and orientation of these subunits. Our results showed that the subunit configuration of the same repeat number of VNTR locus from different populations were, in fact, virtually identical. It implies that most of the VNTR alleles existed before dispersion of modern humans outside Africa. Further analyses indicate that the present diversity profile of this locus in worldwide populations is generated from the effect of migration of different tribes and neutral evolution. Our findings do not support the hypothesis that the origin of the VNTR alleles were arisen by independent (separate) mutation events and caused by differential allele advantage and natural selection as suggested by previous report based on SNP data.

Wang, Hua-Wei; Tang, Nelson Leung-Sang; Zhang, Ya-Ping

2012-01-01

250

Function and structure in early modern muscular mechanics. Four episodes and a dialogue between Stensen and Borelli on two chief muscular systems.  

PubMed

The dispute on the movement of skeletal muscles in 1667 between Giovanni Alfonso Borelli, who maintained the ancient movement caused by inflation theory, and Niels Stensen (Nicolaus Steno), who proposed the first recorded theory of fibre contraction, had far reaching implications for understanding the relation between muscle morphology and function. A dialogue is reconstructed from citations from the two authors' main works. They had a similar dispute on the movement of the heart along the lines of the debate in the 1630s between William Harvey favouring contraction and René Descartes favouring swelling. Evidence is provided for the delayed general acceptance of fibre contraction in both heart and skeletal muscles. It is shown that the inflation interpretation of muscular mechanics elaborated by Borelli, Johann Bernoulli, his son Daniel, and by others, was maintained from ancient authors and Descartes in part due to a conceptual block resulting from the mechanical philosophy that denied any force of attraction in nature. The alternative theory, that of fibre contraction, was thought of as self-motion, which violated an accepted mechanical principle and therefore was rejected. In the mid-18th century, Albrecht von Haller recorded no microscopic structures in support of inflation. He adopted the view that contraction in fibres of muscles is generated through an 'irritability'. Research on this entity has taken place ever since with a clear preponderance of studies on single fibre properties and subcellular structures. Haller did not, however, refer to the original contribution of Stensen on fibre contraction. Haller even rejected Stensen's functional architecture of skeletal muscle. This structure, now called the unipennate, or semipennate, actuator, was overlooked and had to await confirmation by anatomical rediscovery and pragmatic demonstration through successful applications in computer models of muscular contraction in the 1980s. PMID:9522899

Kardel, T

1997-01-01

251

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

SciTech Connect

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.

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

2012-03-09

252

Origins of power-law degree distribution in the heterogeneity of human activity in social networks  

PubMed Central

The probability distribution of number of ties of an individual in a social network follows a scale-free power-law. However, how this distribution arises has not been conclusively demonstrated in direct analyses of people's actions in social networks. Here, we perform a causal inference analysis and find an underlying cause for this phenomenon. Our analysis indicates that heavy-tailed degree distribution is causally determined by similarly skewed distribution of human activity. Specifically, the degree of an individual is entirely random - following a “maximum entropy attachment” model - except for its mean value which depends deterministically on the volume of the users' activity. This relation cannot be explained by interactive models, like preferential attachment, since the observed actions are not likely to be caused by interactions with other people.

Muchnik, Lev; Pei, Sen; Parra, Lucas C.; Reis, Saulo D. S.; Andrade Jr, Jose S.; Havlin, Shlomo; Makse, Hernan A.

2013-01-01

253

Origin, diversity, and maturation of human antiviral antibodies analyzed by high-throughput sequencing.  

PubMed

Our understanding of how antibodies are generated and function could help develop effective vaccines and antibody-based therapeutics against viruses such as HIV-1, SARS coronavirus (SARS CoV), and Hendra and Nipah viruses (henipaviruses). Although broadly neutralizing antibodies (bnAbs) against the HIV-1 were observed in patients, elicitation of such bnAbs remains a major challenge when compared to other viral targets. We previously hypothesized that HIV-1 could have evolved a strategy to evade the immune system due to absent or very weak binding of germline antibodies to the conserved epitopes that may not be sufficient to initiate and/or maintain an effective immune response. To further explore our hypothesis, we used the 454 sequence analysis of a large naïve library of human IgM antibodies which had been used for selecting antibodies against SARS CoV receptor-binding domain (RBD), and soluble G proteins (sG) of henipaviruses. We found that the human IgM repertoires from the 454 sequencing have diverse germline usages, recombination patterns, junction diversity, and a lower extent of somatic mutation. In this study, we identified antibody maturation intermediates that are related to bnAbs against the HIV-1 and other viruses as observed in normal individuals, and compared their genetic diversity and somatic mutation level along with available structural and functional data. Further computational analysis will provide framework for understanding the underlying genetic and molecular determinants related to maturation pathways of antiviral bnAbs that could be useful for applying novel approaches to the design of effective vaccine immunogens and antibody-based therapeutics. PMID:22876240

Prabakaran, Ponraj; Zhu, Zhongyu; Chen, Weizao; Gong, Rui; Feng, Yang; Streaker, Emily; Dimitrov, Dimiter S

2012-01-01

254

Early Origins of Adult Disease: Approaches for Investigating the Programmable Epigenome in Humans, Nonhuman Primates, and Rodents  

PubMed Central

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.

Ganu, Radhika S.; Harris, R. Alan; Collins, Kiara; Aagaard, Kjersti M.

2012-01-01

255

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

PubMed Central

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.

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

256

A cell of origin gene signature indicates human bladder cancer has distinct cellular progenitors.  

PubMed

There are two distinct forms of urothelial (bladder) cancer: muscle-invasive (MI) and nonmuscle invasive (NMI) disease. Since it is currently believed that bladder cancer arises by transformation of urothelial cells of the basal layer, bladder cancer stem cells (CSCs) have been isolated based on expression markers found in such cells. However, these CSCs have only been identified in MI tumors raising the intriguing hypothesis that NMI tumor progenitors do not arise from the basal compartment. To test this hypothesis, we carried out genome-wide expression profiling of laser capture microdissected basal and umbrella cells, the two most histologically distinct cell types in normal urothelium and developed a cell of origin (COO) gene signature that distinguishes these. The COO signature was a better predictor of stage and survival than other bladder, generic, or breast CSC signatures and bladder cell differentiation markers in multiple patient cohorts. To assess whether NMI and MI tumors arise from a distinct progenitor cell (DPC) or common progenitor cell, we developed a novel statistical framework that predicts COO score as a function of known genetic alterations (TP53, HRAS, KDM6A, and FGFR3) that drive either MI or NMI bladder cancer and compared this to the observed COO score of the tumor. Analysis of 874 patients in five cohorts established the DPC model as the best fit to the available data. This observation supports distinct progenitor cells in NMI and MI tumors and provides a paradigm shift in our understanding of bladder cancer biology that has significant diagnostic and therapeutic implications. PMID:24357085

Dancik, Garrett M; Owens, Charles R; Iczkowski, Kenneth A; Theodorescu, Dan

2014-04-01

257

Human exposure to endotoxins and fecal indicators originating from water features.  

PubMed

Exposure to contaminated aerosols and water originating from water features may pose public health risks. Endotoxins in air and water and fecal bacteria in water of water features were measured as markers for exposure to microbial cell debris and enteric pathogens, respectively. Information was collected about wind direction, wind force, distance to the water feature, the height of the water feature and the tangibility of water spray. The mean concentration of endotoxins in air nearby and in water of 31 water features was 10 endotoxin units (EU)/m(3) (Geometric Mean (GM), range 0-85.5 EU/m(3) air) and 773 EU/mL (GM, range 9-18,170 EU/mL water), respectively. Such mean concentrations may be associated with respiratory health effects. The water quality of 26 of 88 water features was poor when compared to requirements for recreational water in the Bathing Water Directive 2006/7/EC. Concentrations greater than 1000 colony forming units (cfu) Escherichia coli per 100 mL and greater than 400 cfu intestinal enterococci per 100 mL increase the probability of acquiring gastrointestinal health complaints. Regression analyses showed that the endotoxin concentration in air was significantly influenced by the concentration of endotoxin in water, the distance to the water feature and the tangibility of water spray. Exposure to air and water near water features was shown to lead to exposure to endotoxins and fecal bacteria. The potential health risks resulting from such exposure to water features may be estimated by a quantitative microbial risk assessment (QMRA), however, such QMRA would require quantitative data on pathogen concentrations, exposure volumes and dose-response relationships. The present study provides estimates for aerosolisation ratios that can be used as input for QMRA to quantify exposure and to determine infection risks from exposure to water features. PMID:24231029

de Man, H; Heederik, D D J; Leenen, E J T M; de Roda Husman, A M; Spithoven, J J G; van Knapen, F

2014-03-15

258

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

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…

Groen, Janet; Hyland-Russell, Tara

2012-01-01

259

In vitro inhibition of Escherichia coli O157:H7 by bifidobacterial strains of human origin.  

PubMed

The ability of bifidobacteria isolated from infant feces to inhibit enterohemorrhagic Escherichia coli serotype O157:H7 in vitro and reduce its adhesion to human enterocyte-like Caco-2 cells was evaluated in comparison to American Type Culture Collection bifidobacterial reference strains. Five Bifidobacterium isolates from infant feces were identified and characterized by morphology, fructose-6-phosphate phosphoketolase (F6PPK) assay, polymerase chain reaction using bifidobacterial 16S rDNA specific primers, carbohydrate fermentation patterns, resistance to lysozyme, acid, bile and hydrogen peroxide as well as their ability to inhibit E. coli O157:H7 using the agar spot technique. Infant isolates showed greater resistance to bile, acid, lysozyme and more antimicrobial activity against E. coli O157:H7 than ATCC strains. Two infant isolates identified as B. bifidum RBL 71 and B. bifidum RBL 460 showed good adhesion and significant potential for reducing adhesion of E. coli O157:H7 to Caco-2 cells. This effect was dependent on bifidobacterial cell concentration. These results show that bifidobacteria isolated from infants may be useful for improving probiotic formulae with respect to protection against E. coli O157:H7 infection. PMID:15033269

Gagnon, Mélanie; Kheadr, Ehab E; Le Blay, Gwenaëlle; Fliss, Ismaïl

2004-04-01

260

Origin, Possible Function and Fate of "Follicular Cells" in the Anterior Lobe of the Human Pituitary  

PubMed Central

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

Horvath, E.; Kovacs, K.; Penz, G.; Ezrin, C.

1974-01-01

261

[Immunophysiological mechanism of origin and maintenance of tumor growth in humans].  

PubMed

A new concept of malignant tumor growth is presented. In consists in the fact that the tumor cells in the body occur in specific immune tolerance. As s result, they form around the center of regeneration, which consists of activated towards the regeneration cells of the immune system, which support the formation and growth of the tumor. In the early stages of differentiation, precancerous cells are not able to attract immune cells and form the focus of regeneration, so the majority of them die. At the outbreak of chronic inflammation, which contains a high percentage of regeneration of activated immune cells, the conditions exists for the formation of a focus of regeneration and, hence, growth and activation of precancerous cells and their transformation into high-grade malignant cells. This concept defines new approaches to treatment. For effective cancer therapy is necessary to neutralize the regenerator chamber in the tumor tissue. The effectiveness of the regeneration of damaged human tissues can be achieved through regenerator chamber similar to that created in the malignant tissue, and the introduction of a stem cell. PMID:20803946

Lebedev, K A; Poniakina, I D

2010-01-01

262

Giardia duodenalis sub-Assemblage of animal and human origin in horses.  

PubMed

In order to evaluate infection occurrence and the potential zoonotic role of horse isolates of Giardia duodenalis, 431 individual fecal samples were genetically characterized by PCR tests -coupled sequencing and phylogenetic analysis. Thirty-seven (8.6%) animals resulted infected by different Assemblage. The presence of sub-Assemblage was assessed by characterizing the ?-giardin gene for 16 of the 37 positive horses. Ten isolates showed 99.6% to 100% homology with the sub-Assemblage described as B1-2 and B1-6, three Assemblage A showed 99.8% homology with sub-Assemblage A1, while one Assemblage E displayed 98.8% homology with sub-Assemblage E3. Furthermore, one isolate characterized as Assemblage A showed 99.6% homology with the sub-Assemblage B1-2 and one characterized as E was 100% identical with sub-Assemblage B1-6. These results demonstrate the presence of both animal and human sub-Assemblage of G. duodenalis in horses from Italy. Epidemiological and sanitary implications are discussed. PMID:22771626

Traversa, Donato; Otranto, Domenico; Milillo, Piermarino; Latrofa, Maria Stefania; Giangaspero, Annunziata; Di Cesare, Angela; Paoletti, Barbara

2012-12-01

263

Mouse and human homologues of the yeast origin of replication recognition complex subunit ORC2 and chromosomal localization of the cognate human gene ORC2L  

SciTech Connect

ORC2 is a subunit of the origin recognition complex in yeast and has been implicated in the initiation of DNA replication and transcriptional silencing. We have isolated mouse and human cDNA clones encoding proteins with 47.9 and 46.3% similarity, respectively, to yeast ORC2. This degree of similarity and the alignment of sequences suggest that these clones may represent a mammalian ORC2 homologue. The existence of such a homologue would, in turn, suggest the existence of a mammalian origin recognition complex, similar to that found in yeast. Although Northern blot analysis of various adult mouse tissues found the highest levels of expression of ORC2-like (ORC2L) RNA in testes, strong signals did not always correspond to tissues in which high levels of DNA replication would be expected. This finding may reflect functional roles of ORC2L distinct from those that it may play in DNA replication. Analyses of somatic cell hybrid DNA and fluorescence in situ hybridization were employed to map the human ORC2L gene to chromosome 2q33. 14 refs., 2 figs.

Takahara, Kazuhiko; Bong, M.; Brevard, R. [Univ. of Wisconsin, Madison, WI (United States)] [and others] [Univ. of Wisconsin, Madison, WI (United States); and others

1996-01-01

264

Genome-Wide and Paternal Diversity Reveal a Recent Origin of Human Populations in North Africa  

PubMed Central

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.

Martinez-Cruz, Begona; Zalloua, Pierre; Benammar Elgaaied, Amel; Comas, David

2013-01-01

265

Human adult stem cells from diverse origins: an overview from multiparametric immunophenotyping to clinical applications.  

PubMed

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

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

266

Relationship between human physiological parameters and geomagnetic variations of solar origin  

NASA Astrophysics Data System (ADS)

Results presented concern influence of increased geomagnetic activity on some human physiological parameters. The blood pressure and heart rate of 86 volunteers were measured on working days in autumn 2001 (01/10 09/11) and in spring 2002 (08/04 28/05). These periods were chosen because of maximal expected geomagnetic activity. Altogether 2799 recordings were obtained and analysed. Questionnaire information about subjective psycho-physiological complaints was also gathered. MANOVA was employed to check the significance of the influence of three factors on the physiological parameters under consideration. The 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 of the group examined reached 9%. 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 and the highest sensitivity was revealed for the hypertensive females.

Dimitrova, S.

267

A Novel Human-Infection-Derived Bacterium Provides Insights into the Evolutionary Origins of Mutualistic Insect-Bacterial Symbioses  

PubMed Central

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.

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

268

Human T-lymphotropic virus type 1 in coastal natives of British Columbia: phylogenetic affinities and possible origins.  

PubMed Central

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.

Picard, F J; Coulthart, M B; Oger, J; King, E E; Kim, S; Arp, J; Rice, G P; Dekaban, G A

1995-01-01

269

Transcriptional activation of the human papillomavirus type 5 and 16 long control region in cells from cutaneous and mucosal origin  

PubMed Central

Human papillomavirus type-16 (HPV-16) infects mucosal epithelium and is the most common type found in cervical cancer. HPV-5 infects cornified epithelium and is the most common type found on normal skin and belongs to the types frequently associated with skin cancers of Epidermodysplasia verruciformis patients. One factor by which this anatomical tropism could be determined is the regulation of HPV gene expression in the host cell. The HPV long control region (LCR) contains cis-responsive elements that regulate HPV transcription and the epithelial tropism of HPV is determined by epithelial specific constitutive enhancers in the LCR. Since HPV-16 and other types infecting the mucosa differ in host cell from HPV types infecting skin, it has been hypothesized that it is the combination of ubiquitous transcription factors working in concert in the host cell that determines the cell-type-specific expression. To study if HPV tropism could be determined by differences in transcriptional regulation we have cloned the transcriptional regulating region, LCR, from HPV-16 and HPV-5 and studied the activation of a reporter gene in cell lines with different origin. To analyse promoter activity we transfected the plasmids into four different cell lines; HaCaT, C33A, NIKS and W12E and the efficiency of HPV-5 and HPV-16 LCR in the different cell lines was compared. In HaCaT cells, with a skin origin, the HPV-5 LCR was two-fold more efficient in transcriptional activation compared to the HPV-16 LCR. In cervical W12E cells the HPV-16 LCR was almost 2-fold more effective in activating transcription compared to the HPV-5 LCR. The ability to initiate transcription in the other cell lines was independent on cell origin and HPV-type.

Mistry, Nitesh; Simonsson, Monika; Evander, Magnus

2007-01-01

270

Molecular and pathogenic characterization of Salmonella enterica serovar Bovismorbificans strains of animal, environmental, food, and human origin in Hungary.  

PubMed

In this study, we characterized 110 strains of Salmonella enterica serovar Bovismorbificans contaminating environment, animals, food of animal origin, and human, to assess their significance along the food chain in Hungary. Additionally, five strains from Germany were tested for comparative purposes. Characterization involved antibiotic susceptibility testing, class 1 integron detection by polymerase chain reaction, plasmid profiling, virulotyping (using virulence gene-specific polymerase chain reactions), and pulsed-field gel electrophoresis. Pathogenic potential of selected strains was tested in orally infected 1-day-old specific pathogen-free chicks. Eighty-two percent of the strains were susceptible to the 16 antibiotics tested, and none of them had class 1 integron. A multidrug-resistant human isolate harbored a bla(SHV5)-type extended-spectrum beta-lactamase gene, first reported in this serotype. All the strains possessed avrA, ssaQ, mgtC, spi4, and sopB genes indicating the presence of Salmonella pathogenicity islands 1-5, respectively, missed the phage-related genes sopE and gipA, but retained the phage-related gene sodC1. An approximately 90 kb large plasmid was characteristic to 80% of the strains, all of which carried the spvC gene. In vivo colonization testing of four selected strains in 1-day-old chicks resulted in significantly reduced liver and spleen colonization ability as compared with the Salmonella Enteritidis control strain, whereas their caecal colonization ability differed less from that of Salmonella Enteritidis. Pulsed-field gel electrophoresis data revealed the dominance of two pulsotypes (C2 and C5) without any specific temporal, geographical, and/or source-related linkages. The results show that Salmonella Bovismorbificans studied here are less invasive than Salmonella Enteritidis, but they may colonize and persist in several animal species and successfully contaminate meat products of different animal origin in Hungary. PMID:20001326

Nógrády, Noémi; Imre, Ariel; Kostyák, Agnes; Tóth, Akos; Nagy, Béla

2010-05-01

271

Aberrant firing of replication origins potentially explains intragenic nonrecurrent rearrangements within genes, including the human DMD gene  

PubMed Central

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.

Ankala, Arunkanth; Kohn, Jordan N.; Hegde, Anisha; Meka, Arjun; Ephrem, Chin Lip Hon; Askree, Syed H.; Bhide, Shruti; Hegde, Madhuri R.

2012-01-01

272

iPS Cells Reprogrammed From Human Mesenchymal-Like Stem/Progenitor Cells of Dental Tissue Origin  

PubMed Central

Generation of induced pluripotent stem (iPS) cells holds a great promise for regenerative medicine and other aspects of clinical applications. Many types of cells have been successfully reprogrammed into iPS cells in the mouse system; however, reprogramming human cells have been more difficult. To date, human dermal fibroblasts are the most accessible and feasible cell source for iPS generation. Dental tissues derived from ectomesenchyme harbor mesenchymal-like stem/progenitor cells and some of the tissues have been treated as biomedical wastes, for example, exfoliated primary teeth and extracted third molars. We asked whether stem/progenitor cells from discarded dental tissues can be reprogrammed into iPS cells. The 4 factors Lin28/Nanog/Oct4/Sox2 or c-Myc/Klf4/Oct4/Sox2 carried by viral vectors were used to reprogram 3 different dental stem/progenitor cells: stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), and dental pulp stem cells (DPSCs). We showed that all 3 can be reprogrammed into iPS cells and appeared to be at a higher rate than fibroblasts. They exhibited a morphology indistinguishable from human embryonic stem (hES) cells in cultures and expressed hES cell markers SSEA-4, TRA-1-60, TRA-1-80, TRA-2-49, Nanog, Oct4, and Sox2. They formed embryoid bodies in vitro and teratomas in vivo containing tissues of all 3 germ layers. We conclude that cells of ectomesenchymal origin serve as an excellent alternative source for generating iPS cells.

2010-01-01

273

Early Modern Language Programs in Hungary.  

ERIC Educational Resources Information Center

Provides insight into the teaching of modern languages to young learners in Hungary. Demonstrates how different the educational context is from the United States and how the Prussian educational tradition still influences today's processes. Also discussed are language teachers, resources of early language programs, young learners' attitudes and…

Nikolov, Marianne

2000-01-01

274

Worlds and Systems in Early Modern Europe  

NASA Astrophysics Data System (ADS)

The structure, formation and evolution of the Universe were some of the main topics in the scientific debates during the 17th and 18th centuries in Europe. They involved novel ideas on the cosmos, which concerned aspects that were not considered before so emphatically, and which were fundamental for the future development of astronomy. This paper presents a brief account of several milestones within the gradual definition of pre-galactic systems: the historical role of the tradition of the plurality of worlds, the significance of Descartes, and the introduction of the Milky Way and nebulae in the discourses around the cosmic structure.

Ayala, L.

2013-04-01

275

Early Modern Language Learning: Conditions of Success.  

ERIC Educational Resources Information Center

A language education specialist who has studied elementary school second language programs, primarily in France but also in other European countries, outlines the factors he has found contributing to program success and makes recommendations for further development of second language education in Europe. Seven conditions for effective programs of…

Girard, Denis

276

The origin, evolution, and functional impact of short insertion-deletion variants identified in 179 human genomes  

PubMed Central

Short insertions and deletions (indels) are the second most abundant form of human genetic variation, but our understanding of their origins and functional effects lags behind that of other types of variants. Using population-scale sequencing, we have identified a high-quality set of 1.6 million indels from 179 individuals representing three diverse human populations. We show that rates of indel mutagenesis are highly heterogeneous, with 43%–48% of indels occurring in 4.03% of the genome, whereas in the remaining 96% their prevalence is 16 times lower than SNPs. Polymerase slippage can explain upwards of three-fourths of all indels, with the remainder being mostly simple deletions in complex sequence. However, insertions do occur and are significantly associated with pseudo-palindromic sequence features compatible with the fork stalling and template switching (FoSTeS) mechanism more commonly associated with large structural variations. We introduce a quantitative model of polymerase slippage, which enables us to identify indel-hypermutagenic protein-coding genes, some of which are associated with recurrent mutations leading to disease. Accounting for mutational rate heterogeneity due to sequence context, we find that indels across functional sequence are generally subject to stronger purifying selection than SNPs. We find that indel length modulates selection strength, and that indels affecting multiple functionally constrained nucleotides undergo stronger purifying selection. We further find that indels are enriched in associations with gene expression and find evidence for a contribution of nonsense-mediated decay. Finally, we show that indels can be integrated in existing genome-wide association studies (GWAS); although we do not find direct evidence that potentially causal protein-coding indels are enriched with associations to known disease-associated SNPs, our findings suggest that the causal variant underlying some of these associations may be indels.

Montgomery, Stephen B.; Goode, David L.; Kvikstad, Erika; Albers, Cornelis A.; Zhang, Zhengdong D.; Mu, Xinmeng Jasmine; Ananda, Guruprasad; Howie, Bryan; Karczewski, Konrad J.; Smith, Kevin S.; Anaya, Vanessa; Richardson, Rhea; Davis, Joe; MacArthur, Daniel G.; Sidow, Arend; Duret, Laurent; Gerstein, Mark; Makova, Kateryna D.; Marchini, Jonathan; McVean, Gil; Lunter, Gerton

2013-01-01

277

Adhesion of Human and Animal Escherichia coli Strains in Association with Their Virulence-Associated Genes and Phylogenetic Origins  

PubMed Central

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.

Frommel, Ulrike; Lehmann, Werner; Rodiger, Stefan; Bohm, Alexander; Nitschke, Jorg; Weinreich, Jorg; Gross, Julia; Roggenbuck, Dirk; Zinke, Olaf; Ansorge, Hermann; Vogel, Steffen; Klemm, Per; Wex, Thomas; Schroder, Christian; Wieler, Lothar H.

2013-01-01

278

The Early Aurignacian human remains from La Quina-Aval (France).  

PubMed

There is a dearth of diagnostic human remains securely associated with the Early Aurignacian of western Europe, despite the presence of similarly aged early modern human remains from further east. One small and fragmentary sample of such remains consists of the two partial immature mandibles plus teeth from the Early Aurignacian of La Quina-Aval, Charente, France. The La Quina-Aval 4 mandible exhibits a prominent anterior symphyseal tuber symphyseos on a vertical symphysis and a narrow anterior dental arcade, both features of early modern humans. The dental remains from La Quina-Aval 1 to 4 (a dm(1), 2 dm(2), a P(4) and a P(4)) are unexceptional in size and present occlusal configurations that combine early modern human features with a few retained ancestral ones. Securely dated to ~33 ka (14)C BP (~38 ka cal BP), these remains serve to confirm the association of early modern humans with the Early Aurignacian in western Europe. PMID:22459765

Verna, Christine; Dujardin, Véronique; Trinkaus, Erik

2012-05-01

279

A Lactobacillus acidophilus Strain of Human Gastrointestinal Microbiota Origin Elicits Killing of Enterovirulent Salmonella enterica Serovar Typhimurium by Triggering Lethal Bacterial Membrane Damage  

Microsoft Academic Search

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)

Marie-Helene Coconnier-Polter; Vanessa Lievin-Le Moal; Alain L. Servin

2005-01-01

280

"The city of Hepar": rituals, gastronomy, and politics at the origins of the modern names for the liver.  

PubMed

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

Riva, Michele Augusto; Riva, Enrica; Spicci, Mauro; Strazzabosco, Mario; Giovannini, Marcello; Cesana, Giancarlo

2011-11-01

281

Genome-wide mapping of human DNA-replication origins: Levels of transcription at ORC1 sites regulate origin selection and replication timing  

PubMed Central

We report the genome-wide mapping of ORC1 binding sites in mammals, by chromatin immunoprecipitation and parallel sequencing (ChIP-seq). ORC1 binding sites in HeLa cells were validated as active DNA replication origins (ORIs) using Repli-seq, a method that allows identification of ORI-containing regions by parallel sequencing of temporally ordered replicating DNA. ORC1 sites were universally associated with transcription start sites (TSSs) of coding or noncoding RNAs (ncRNAs). Transcription levels at the ORC1 sites directly correlated with replication timing, suggesting the existence of two classes of ORIs: those associated with moderate/high transcription levels (?1 RNA copy/cell), firing in early S and mapping to the TSSs of coding RNAs; and those associated with low transcription levels (<1 RNA copy/cell), firing throughout the entire S and mapping to TSSs of ncRNAs. These findings are compatible with a scenario whereby TSS expression levels influence the efficiency of ORC1 recruitment at G1 and the probability of firing during S.

Dellino, Gaetano Ivan; Cittaro, Davide; Piccioni, Rossana; Luzi, Lucilla; Banfi, Stefania; Segalla, Simona; Cesaroni, Matteo; Mendoza-Maldonado, Ramiro; Giacca, Mauro; Pelicci, Pier Giuseppe

2013-01-01

282

Karyotype and ultrastructure of a colony stimulating factor (CSF) producing cell line (5637) originated from a carcinoma of the human urinary bladder  

Microsoft Academic Search

The cell line 5637 which originated from a human urinary bladder carcinoma is known to produce GM-CSF and Multi-CSF ectopically. Determination of cell surface antigens defined by monoclonal antibodies was recently reported [6]. Here we report on the ultrastructure and karyology of this CSF secreting cell line. At the ultrastructural level the monolayer in vitro culture and the solid tumors

K.-H. Pflüger; H.-D. Probeck; G. Adler; D. Stach-Machado; H. Kapmeyer; K. Havemann

1986-01-01

283

[Screening and identification of 36 new STR loci in human Y chromosome].  

PubMed

133 candidate Y-STR loci were selected from NCBI STS database or by bioinformatics analysis in human Y-chromosome sequence, and were screened among 48 DNA samples around the world. Forty-one Y-STRs with high allelic frequency were validated, 36 of which were first reported. Two hundred haplotypes of the 41 STRs were identified among 200 randomly sampled male individuals in Shanghai, indicating 100% inter-individual discrimination. By network analysis of haplotypes of the 41 STRs among nine Jiang-surname male individuals with no consanguinity within 5 generations from a Jiang-surname individual gathering at Jiangshan, Zhejiang Province, and 7 Jiang-surname male individuals from the random shanghai population, 6 Jiang-surname individuals from Jiangshan were close with only 2-4 STR locus difference. These 41 Y-STR loci provide enough information by which individuals from each other with different early modern family origin can be effectively distinguished. This will promote studies on identification of non-lineal relationship in forensics, ancestry location of oversea Chinese, the surname origin and evolution, origin and migration of modern humans and many other studies of Contemporary Anthropology. PMID:23208138

Peng, Dong-Bo; Jiang, Zheng-Wen; Sun, Si-Ping; Li, Cai-Hua; Lu, Da-Ru

2012-11-01

284

The Myth of a Feminist Humanism: Thomas Salter's "The Mirrhor of Modestie".  

ERIC Educational Resources Information Center

A late sixteenth century work articulates one of the most conservative of Early Modern positions on women's education. It is found to contradict the commonly-held idea that a feminist humanism encouraging women to enter the sphere of arts and letters persisted in this period. (MSE)

Holm, Janis Butler

1985-01-01

285

Genomic Study of Replication Initiation in Human Chromosomes Reveals the Influence of Transcription Regulation and Chromatin Structure on Origin Selection  

PubMed Central

DNA replication in metazoans initiates from multiple chromosomal loci called origins. Currently, there are two methods to purify origin-centered nascent strands: lambda exonuclease digestion and anti-bromodeoxyuridine immunoprecipitation. Because both methods have unique strengths and limitations, we purified nascent strands by both methods, hybridized them independently to tiling arrays (1% genome) and compared the data to have an accurate view of genome-wide origin distribution. By this criterion, we identified 150 new origins that were reproducible across the methods. Examination of a subset of these origins by chromatin immunoprecipitation against origin recognition complex (ORC) subunits 2 and 3 showed 93% of initiation peaks to localize at/within 1 kb of ORC binding sites. Correlation of origins with functional elements of the genome revealed origin activity to be significantly enriched around transcription start sites (TSSs). Consistent with proximity to TSSs, we found a third of initiation events to occur at or near the RNA polymerase II binding sites. Interestingly, ?50% of the early origin activity was localized within 5 kb of transcription regulatory factor binding region clusters. The chromatin signatures around the origins were enriched in H3K4-(di- and tri)-methylation and H3 acetylation modifications on histones. Affinity of origins for open chromatin was also reiterated by their proximity to DNAse I-hypersensitive sites. Replication initiation peaks were AT rich, and >50% of the origins mapped to evolutionarily conserved regions of the genome. In summary, these findings indicate that replication initiation is influenced by transcription initiation and regulation as well as chromatin structure.

Karnani, Neerja; Taylor, Christopher M.; Malhotra, Ankit

2010-01-01

286

Bubble-seq analysis of the human genome reveals distinct chromatin-mediated mechanisms for regulating early- and late-firing origins  

PubMed Central

We have devised a method for isolating virtually pure and comprehensive libraries of restriction fragments that contained replication initiation sites (bubbles) in vivo. We have now sequenced and mapped the bubble-containing fragments from GM06990, a near-normal EBV-transformed lymphoblastoid cell line, and have compared origin distributions with a comprehensive replication timing study recently published for this cell line. We find that early-firing origins, which represent ?32% of all origins, overwhelmingly represent zones, associate only marginally with active transcription units, are localized within large domains of open chromatin, and are significantly associated with DNase I hypersensitivity. Origin “density” falls from early- to mid-S-phase, but rises again in late S-phase to levels only 17% lower than in early S-phase. Unexpectedly, late origin density calculated on the 1-Mb scale increases as a function of increasing chromatin compaction. Furthermore, the median efficiency of origins in late-replicating, heterochromatic domains is only 25% lower than in early-replicating euchromatic loci. Thus, the activation of early- and late-firing origins must be regulated by quintessentially different mechanisms. The aggregate data can be unified into a model in which initiation site selection is driven almost entirely by epigenetic factors that fashion both the long-range and local chromatin environments, with underlying DNA sequence and local transcriptional activity playing only minor roles. Importantly, the comprehensive origin map we have prepared for GM06990 overlaps moderately well with origin maps recently reported for the genomes of four different human cell lines based on the distributions of small nascent strands.

Mesner, Larry D.; Valsakumar, Veena; Cieslik, Marcin; Pickin, Rebecca; Hamlin, Joyce L.; Bekiranov, Stefan

2013-01-01

287

Comparison of Variable-Number Tandem-Repeat Markers typing and IS1245 Restriction Fragment Length Polymorphism fingerprinting of Mycobacterium avium subsp. hominissuis from human and porcine origins  

PubMed Central

Background Animal mycobacterioses are regarded as a potential zoonotic risk and cause economical losses world wide. M. avium subsp. hominissuis is a slow-growing subspecies found in mycobacterial infected humans and pigs and therefore rapid and discriminatory typing methods are needed for epidemiological studies. The genetic similarity of M. avium subsp. hominissuis from human and porcine origins using two different typing methods have not been studied earlier. The objective of this study was to compare the IS1245 RFLP pattern and MIRU-VNTR typing to study the genetic relatedness of M. avium strains isolated from slaughter pigs and humans in Finland with regard to public health aspects. Methods A novel PCR-based genotyping method, variable number tandem repeat (VNTR) typing of eight mycobacterial interspersed repetitive units (MIRUs), was evaluated for its ability to characterize Finnish Mycobacterium avium subsp. hominissuis strains isolated from pigs (n = 16) and humans (n = 13) and the results were compared with those obtained by the conventional IS1245 RFLP method. Results The MIRU-VNTR results showed a discriminatory index (DI) of 0,92 and the IS1245 RFLP resulted in DI 0,98. The combined DI for both methods was 0,98. The MIRU-VNTR test has the advantages of being simple, reproducible, non-subjective, which makes it suitable for large-scale screening of M. avium strains. Conclusions Both typing methods demonstrated a high degree of similarity between the strains of human and porcine origin. The parallel application of the methods adds epidemiological value to the comparison of the strains and their origins. The present approach and results support the hypothesis that there is a common source of M. avium subsp. hominissuis infection for pigs and humans or alternatively one species may be the infective source to the other.

2010-01-01

288

Chromatin Association of Human Origin Recognition Complex, Cdc6, and Minichromosome Maintenance Proteins during the Cell Cycle: Assembly of Prereplication Complexes in Late Mitosis  

Microsoft Academic Search

Evidence obtained from studies with yeast and Xenopus indicate that the initiation of DNA replication is a multistep process. The origin recognition complex (ORC), Cdc6p, and minichromosome maintenance (MCM) proteins are required for establishing prereplication complexes, upon which initiation is triggered by the activation of cyclin-dependent kinases and the Dbf4p-dependent kinase Cdc7p. The identification of human homologues of these replication

JUAN MENDEZ; BRUCE STILLMAN

2000-01-01

289

Genetically Matched Human iPS Cells Reveal that Propensity for Cartilage and Bone Differentiation Differs with Clones, not Cell Type of Origin  

PubMed Central

Background For regenerative therapy using induced pluripotent stem cell (iPSC) technology, cell type of origin to be reprogrammed should be chosen based on accessibility and reprogramming efficiency. Some studies report that iPSCs exhibited a preference for differentiation into their original cell lineages, while others did not. Therefore, the type of cell which is most appropriate as a source for iPSCs needs to be clarified. Methodology/Principal Findings Genetically matched human iPSCs from different origins were generated using bone marrow stromal cells (BMSCs) and dermal fibroblasts (DFs) of the same donor, and global gene expression profile, DNA methylation status, and differentiation properties into the chondrogenic and osteogenic lineage of each clone were analyzed. Although genome-wide profiling of DNA methylation suggested tissue memory in iPSCs, genes expressed differentially in BMSCs and DFs were equally silenced in our bona fide iPSCs. After cell-autonomous and induced differentiation, each iPSC clone exhibited various differentiation properties, which did not correlate with cell-of-origin. Conclusions/Significance The reprogramming process may remove the difference between DFs and BMSCs at least for chondrogenic and osteogenic differentiation. Qualified and genetically matched human iPSC clone sets established in this study are valuable resources for further basic study of clonal differences.

Nasu, Akira; Ikeya, Makoto; Yamamoto, Takuya; Watanabe, Akira; Jin, Yonghui; Matsumoto, Yoshihisa; Hayakawa, Kazuo; Amano, Naoki; Sato, Shingo; Osafune, Kenji; Aoyama, Tomoki; Nakamura, Takashi; Kato, Tomohisa; Toguchida, Junya

2013-01-01

290

Human antibodies recognizing the envelope glycoprotein of the baboon endogenous virus BaEV are of heterophil origin  

Microsoft Academic Search

Human sera were previously shown to possess antibodies capable of recognizing purified retrovirus envelope glycoproteins. In an extension of earlier studies we investigated sera from various groups of patients for an immune reaction against purified glycoprotein of the baboon endogenous virus BaEV. Reproducible demonstrations of oncovirus-like particles in human teratocarcinomas focused our main interest on sera from patients with testicular

Dorothee Wernicke; Reinhard Kurth

1981-01-01

291

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...

292

Differences in biofilm formation and virulence factors between clinical and fecal enterococcal isolates of human and animal origin.  

PubMed

The present study investigated the possible correlation between carriage of the virulence genes esp and fsrb, production of hemolysin and gelatinase and biofilm formation in human vs. animal enterococcal isolates. A collection of 219 enterococcal isolates recovered from clinical and fecal surveillance samples of hospitalized patients and 132 isolates from animal feces were studied. Isolates were tested for hemolysin and gelatinase phenotypically and for quantitative biofilm production by a microtitre method. Genes esp and fsrb were detected by PCR. Human Enterococcus faecium and Enterococcus faecalis isolates from both surveillance and clinical samples produced biofilm significantly more often than animal isolates (P < 0.0001 for both species). The quantity of biofilm did not differ significantly between human and animal isolates, while was significantly higher in esp-positive compared with esp-negative human E. faecium isolates (P < 0.0001). The frequency of esp gene carriage was significantly higher in human compared with animal E. faecium and E. faecalis isolates (P < 0.0001). The gene fsrb was detected significantly more often in animal than human E. faecium isolates (P 0.004). Hemolysin production was significantly more common in human clinical compared with animal E. faecalis isolates (P < 0.0001). Similar proportions of animal and human E. faecalis produced gelatinase, which was significantly correlated with the presence of fsrb gene (P < 0.0001) in both human clinical and animal E. faecalis isolates. The hemolysin trait did not exhibit any correlation with the presence of esp and fsrb genes, but appeared to be linked with enhanced quantity of biofilm production in both human clinical and animal E. faecalis isolates. Production of gelatinase was associated with the proportion and the degree of biofilm production mainly in animal E. faecalis isolates. PMID:22445820

Tsikrikonis, Giorgos; Maniatis, Antonios N; Labrou, Maria; Ntokou, Eleni; Michail, Giorgos; Daponte, Alexandros; Stathopoulos, Constantinos; Tsakris, Athanassios; Pournaras, Spyros

2012-06-01

293

Evolution of Substrate Specificity in the Rok Superfamily and the Origin of Allosteric Regulation in Human Pancreatic Glucokinase  

Microsoft Academic Search

Sugar kinases are enzymes known to catalyze the phosphorylation of different sugar substrates. The sugar kinases encompassed by the ROK (repressor, open reading frame, kinase) superfamily offer a unique opportunity to explore the evolutionary origins of enzyme specificity. We probed evolutionary events that occur during the optimization of glucokinase activity in two members of the ROK superfamily, Alsk and NanK,

Mioara Larion

2009-01-01

294

Comparative organization and the origin of noncoding regulatory RNA genes from X-chromosome inactivation center of human and mouse  

Microsoft Academic Search

After the radiation of primates and rodents, the evolution of X-chromosome inactivation centers in human and mouse (XIC\\/Xic)\\u000a followed two different directions. Human XIC followed the pathway towards transposon accumulation (the repeat proportion in\\u000a the center constitutes 72%), especially LINEs, which prevail in the center. On the contrary, mouse Xic eliminated long repeats\\u000a and accumulated species-specific SINEs (the repeat proportion

N. N. Kolesnikov; E. A. Elisaphenko

2010-01-01

295

Localization and origin of cardiac CD117-positive cells: identification of a population of epicardially-derived cells in adult human heart.  

PubMed

During heart morphogenesis, epicardial cells undergo epithelial-mesenchymal transition giving origin to a population of epicardially derived cells that play a crucial role in the development of most cardiac cell lineages. Considering the hypothesis that epithelial-mesenchymal transition of epicardial mesothelium can generate cardiac primitive cells in the adult heart, we have examined in vivo and in vitro the epicardium and subepicardium of normal human adult hearts and of pathological hearts from patients with chronic ischemic heart failure for the presence of CD117-positive cells with epithelial and mesenchymal markers expression. The number of CD117-positive cells increased significantly in the subepicardium of pathological hearts and sloped down towards myocardium, remaining still elevated with respect to normal hearts. While cells with typical epithelial proteins expression formed an intact layer on the surface of the normal hearts, CD117-positive cells were localized mainly in the subepicardium and expressed mesenchymal markers in the pathological hearts. Epithelial-mesenchymal transition, induced in vitro by several growth factors known to accumulate in the ischemic myocardium, gave origin to epicardially-derived cells with CD117 expression. These data support the hypothesis of epicardial origin of cardiac primitive cells in the adult human heart. PMID:21072993

Di Meglio, Franca; Castaldo, Clotilde; Nurzynska, Daria; Miraglia, Rita; Romano, Veronica; Russolillo, Veronica; Giuseppina, Langella; Vosa, Carlo; Montagnani, Stefania

2010-01-01

296

Ethnic divergence and linkage disequilibrium of novel SNPs in the human NLI-IF gene: evidence of human origin and lack of association with tuberculosis susceptibility  

Microsoft Academic Search

Sequence variation in the human genome has been used as a tool in studying human diseases and the evolutionary history of\\u000a man. A human inherited predisposition to tuberculosis has been suggested and studied; however, genetic mechanisms are still\\u000a ambiguous. In the present study, we scanned the regulatory and coding region of Nuclear LIM Interactor-Interacting Factor\\u000a gene (NLI-IF), which is physically

Xin Ma; John Wright; Shujun Dou; Paul Olsen; Larry Teeter; Gerald Adams; Edward Graviss

2002-01-01

297

Novel avian-origin influenza A (H7N9) virus attaches to epithelium in both upper and lower respiratory tract of humans.  

PubMed

Influenza A viruses from animal reservoirs have the capacity to adapt to humans and cause influenza pandemics. The occurrence of an influenza pandemic requires efficient virus transmission among humans, which is associated with virus attachment to the upper respiratory tract. Pandemic severity depends on virus ability to cause pneumonia, which is associated with virus attachment to the lower respiratory tract. Recently, a novel avian-origin H7N9 influenza A virus with unknown pandemic potential emerged in humans. We determined the pattern of attachment of two genetically engineered viruses containing the hemagglutinin of either influenza virus A/Shanghai/1/13 or A/Anhui/1/13 to formalin-fixed human respiratory tract tissues using histochemical analysis. Our results show that the emerging H7N9 virus attached moderately or abundantly to both upper and lower respiratory tract, a pattern not seen before for avian influenza A viruses. With the caveat that virus attachment is only the first step in the virus replication cycle, these results suggest that the emerging H7N9 virus has the potential both to transmit efficiently among humans and to cause severe pneumonia. PMID:24029490

van Riel, Debby; Leijten, Lonneke M E; de Graaf, Miranda; Siegers, Jurre Y; Short, Kirsty R; Spronken, Monique I J; Schrauwen, Eefje J A; Fouchier, Ron A M; Osterhaus, Albert D M E; Kuiken, Thijs

2013-10-01

298

Alphaherpesvirus origin-binding protein homolog encoded by human herpesvirus 6B, a betaherpesvirus, binds to nucleotide sequences that are similar to ori regions of alphaherpesviruses.  

PubMed Central

We previously identified a human herpesvirus 6B (HHV-6B) homolog of the alphaherpesvirus origin-binding protein (OBP), exemplified by the herpes simplex virus type 1 UL9 gene product. This finding is of particular interest because HHV-6B is otherwise more closely related to members of the betaherpesvirus subfamily. The prototypic betaherpesvirus, human cytomegalovirus, does not encode an obvious OBP homolog and contains a more complex origin of replication than do alphaherpesviruses. Thus, analysis of the function of the HHV-6B OBP homolog is essential for understanding the mechanism of HHV-6B DNA replication initiation. The HHV-6B OBP homolog, OBPH6B, was expressed in vitro by coupled transcription and translation and in insect cells by infection with recombinant baculoviruses. The expressed protein bound to two DNA sequences located upstream of the HHV-6B major DNA-binding protein gene homolog, within a region that was predicted to serve as an origin of replication on the basis of its sequence properties. The binding sites lie within 23-bp segments and are similar to OBP-binding sites of herpes simplex virus type 1. The two OBPH6B-binding sequences are separated by an AT-rich region and have an imperfect dyad symmetry as do the alphaherpesvirus origin regions. We identified OBPH6B transcripts by reverse transcription PCR in HHV-6B-infected Molt-3 cells. These results suggest that OBPH6B functions in a manner analogous to the alphaherpesvirus OBP and that initiation of HHV-6B DNA replication may resemble that of alphaherpesviruses. Images

Inoue, N; Dambaugh, T R; Rapp, J C; Pellett, P E

1994-01-01

299

Experimental transmission of an autosomal dominant spongiform encephalopathy: does the infectious agent originate in the human genome?  

PubMed Central

Marmosets inoculated intracerebrally with brain tissue from a woman with Gerstmann-Straussler syndrome (an autosomal dominant dementia associated with spongiform change and amyloid deposition) developed an encephalopathy indistinguishable from that seen in marmosets inoculated with brain tissue from a typical case of Creutzfeldt-Jakob disease. As in Huntington's disease, in the pedigree of the patient with Gerstmann-Straussler syndrome women who subsequently developed the illness had increased fecundity. The pathogen in human transmissible dementia may arise from a sequence (which itself sometimes confers a selective advantage) located within the human genome.

Baker, H F; Ridley, R M; Crow, T J

1985-01-01

300

Origin and patterns of the Upper Paleolithic industries in the Korean Peninsula and movement of modern humans in East Asia  

Microsoft Academic Search

Assemblages classified as ‘Upper Paleolithic’ in the Korean peninsula are diverse in their composition, including not only some blade industries but also conventional ones continued from earlier Paleolithic periods. This has often been explained as the result of an indigenous development. However, the ‘heterogenic’ character of Upper Paleolithic industries is the result of the continuing influx of modern human populations

Kidong Bae

2010-01-01

301

The impossible coincidence. A single-species model for the origins of modern human behavior in Europe  

Microsoft Academic Search

Few topics in palaeoanthropology have generated more recent debate than the nature and causes of the remarkable transformation in human behavioral patterns that marked the transition from the Middle to the Upper Paleolithic in Europe.1-11 Those of us who have argued for an effective technological and cultural \\

Paul Mellars

2005-01-01

302

Comparison of Glycopeptide-Resistant Enterococcus faecium Isolates and Glycopeptide Resistance Genes of Human and Animal Origins  

PubMed Central

One hundred thirty-two glycopeptide-resistant Enterococcus faecium (GREF) isolates from different hospitals and pig and poultry farms in Belgium were compared on the basis of (i) their antibiotic susceptibilities, (ii) their SmaI pulsed-field gel electrophoresis (PFGE) patterns, and (iii) the organization of their Tn1546 or related elements in order to detect possible phenotypic and genotypic relationships among both groups of isolates. Human and animal vanA-positive GREF isolates were found to have similar susceptibility patterns; they remained susceptible to gentamicin and were, in general, susceptible to ampicillin. PFGE demonstrated a very high degree of genomic heterogeneity in both groups of isolates. However, indistinguishable isolates were found within different farms or hospitals, and in two instances, epidemiologically unrelated pig and human isolates showed indistinguishable PFGE patterns. In total, eight different transposon types were identified, and all were related to the prototype transposon Tn1546. The two predominant types, Tn1546 and type 2 transposons, which differed at three band positions, were present in both human and animal isolates. Type 2 transposons were significantly associated with pig isolates. The other types were seldom detected. These data suggest a possible exchange of glycopeptide resistance markers between animals and humans.

Descheemaeker, Patrick R. M.; Chapelle, Sabine; Devriese, Luc A.; Butaye, Patrick; Vandamme, Peter; Goossens, Herman

1999-01-01

303

Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants.  

PubMed

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

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

304

Characterization of a Shiga Toxin 2e-Converting Bacteriophage from an Escherichia coli Strain of Human Origin  

Microsoft Academic Search

An infectious Shiga toxin (Stx) 2e-converting bacteriophage (fP27) was isolated from Stx2e-producing Escherichia coli ONT:H2 isolate 2771\\/97 originating from a patient with diarrhea. The phage could be transduced to E. coli laboratory strain DH5a, and we could show that lysogens were able to produce biologically active toxin in a recA-dependent manner. By DNA sequence analysis of a 6,388-bp HindIII restriction

MAITE MUNIESA; JURGEN RECKTENWALD; MARTINA BIELASZEWSKA; HELGE KARCH; HERBERT SCHMIDT

2000-01-01

305

Evolutionary Genetics of Human Enterovirus 71: Origin, Population Dynamics, Natural Selection, and Seasonal Periodicity of the VP1 Gene? †  

PubMed Central

Human enterovirus 71 (EV-71) is one of the major etiologic causes of hand, foot, and mouth disease (HFMD) among young children worldwide, with fatal instances of neurological complications becoming increasingly common. Global VP1 capsid sequences (n = 628) sampled over 4 decades were collected and subjected to comprehensive evolutionary analysis using a suite of phylogenetic and population genetic methods. We estimated that the common ancestor of human EV-71 likely emerged around 1941 (95% confidence interval [CI], 1929 to 1952), subsequently diverging into three genogroups: B, C, and the now extinct genogroup A. Genealogical analysis revealed that diverse lineages of genogroup B and C (subgenogroups B1 to B5 and C1 to C5) have each circulated cryptically in the human population for up to 5 years before causing large HFMD outbreaks, indicating the quiescent persistence of EV-71 in human populations. Estimated phylogenies showed a complex pattern of spatial structure within well-sampled subgenogroups, suggesting endemicity with occasional lineage migration among locations, such that past HFMD epidemics are unlikely to be linked to continuous transmission of a single strain of virus. In addition, rises in genetic diversity are correlated with the onset of epidemics, driven in part by the emergence of novel EV-71 subgenogroups. Using subgenogroup C1 as a model, we observe temporal strain replacement through time, and we investigate the evidence for positive selection at VP1 immunogenic sites. We discuss the consequences of the evolutionary dynamics of EV-71 for vaccine design and compare its phylodynamic behavior with that of influenza virus.

Tee, Kok Keng; Lam, Tommy Tsan-Yuk; Chan, Yoke Fun; Bible, Jon M.; Kamarulzaman, Adeeba; Tong, C. Y. William; Takebe, Yutaka; Pybus, Oliver G.

2010-01-01

306

Interaction of the Retinoblastoma Protein with Orc1 and Its Recruitment to Human Origins of DNA Replication  

Microsoft Academic Search

BackgroundThe retinoblastoma protein (Rb) is a crucial regulator of cell cycle progression by binding with E2F transcription factor and repressing the expression of a variety of genes required for the G1-S phase transition.Methodology\\/Principal FindingsHere we show that Rb and E2F1 directly participate in the control of initiation of DNA replication in human HeLa, U2OS and T98G cells by specifically binding

Ramiro Mendoza-Maldonado; Roberta Paolinelli; Laura Galbiati; Sara Giadrossi; Mauro Giacca; Mary Bryk

2010-01-01

307

Origins of prostaglandin E2: involvements of cyclooxygenase (COX)-1 and COX-2 in human and rat systems.  

PubMed

Prostaglandin (PG) E2 is a major cyclooxygenase (COX) product at inflammatory sites where it contributes to local increases in blood flow, edema formation, and pain sensitization. Using rats in vivo and rat and human blood in vitro, we have examined the roles of COX-1 and COX-2 in the production of PGE2. In anesthetized rats treated with bacterial lipopolysaccharide (LPS) to induce the expression of COX-2, the marked increase in PGE2 production that followed bolus intravenous injection of arachidonic acid (3 mg x kg(-1)) was strongly inhibited by diclofenac but largely unaffected by the COX-2-selective inhibitor DFP (5,5- dimethyl-3-(2-propoxy)-4-methanesulfonylphenyl)-2(5H)-furanone). In rat blood in vitro, aspirin strongly inhibited the production of PGE2 that followed either acute exposure to calcium ionophore, A23187 (calcimycin) (50 microM, 15 min), or incubation with LPS for 18 h. In contrast, human whole blood only produced significant levels of PGE2 when incubated with LPS. Rat leukocytes expressed COX-2 and produced PGE2 when exposed to LPS but not when acutely stimulated with A23187. Rat platelets, but not human platelets, also produced significant amounts of PGE2 when acutely stimulated with A23187. These data show that when exposed to an inflammatory stimulus, rat whole blood produces increased levels of PGE2 through induction of COX-2 in blood leukocytes. Rat blood, unlike human blood, may also produce copious amounts of PGE2 via the actions of COX-1 enzyme constitutively present in platelets. These data may well explain why in rats COX-2-selective inhibitors have been reported not to produce the full anti-inflammatory effects associated with standard nonsteroid anti-inflammatory drugs. PMID:12438520

Giuliano, Francesco; Warner, Timothy D

2002-12-01

308

Antigenic and Genetic Characteristics of Swine-Origin 2009 A(H1N1) Influenza Viruses Circulating in Humans  

Microsoft Academic Search

Since its identification in April 2009, an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Its low genetic diversity

Rebecca J. Garten; C. Todd Davis; Colin A. Russell; Bo Shu; Stephen Lindstrom; Amanda Balish; Wendy M. Sessions; Xiyan Xu; Eugene Skepner; Varough Deyde; Margaret Okomo-Adhiambo; Larisa Gubareva; John Barnes; Catherine B. Smith; Shannon L. Emery; Michael J. Hillman; Pierre Rivailler; James Smagala; Miranda de Graaf; David F. Burke; Ron A. M. Fouchier; Claudia Pappas; Celia M. Alpuche-Aranda; Hugo López-Gatell; Hiram Olivera; Irma López; Christopher A. Myers; Dennis Faix; Patrick J. Blair; Cindy Yu; Kimberly M. Keene; P. David Dotson; David Boxrud; Anthony R. Sambol; Syed H. Abid; Kirsten St. George; Tammy Bannerman; Amanda L. Moore; David J. Stringer; Patricia Blevins; Gail J. Demmler-Harrison; Michele Ginsberg; Paula Kriner; Steve Waterman; Sandra Smole; Hugo F. Guevara; Edward A. Belongia; Patricia A. Clark; Sara T. Beatrice; Ruben Donis; Jacqueline Katz; Lyn Finelli; Carolyn B. Bridges; Michael Shaw; Daniel B. Jernigan; Timothy M. Uyeki; Derek J. Smith; Alexander I. Klimov; Nancy J. Cox

2009-01-01

309

The origin of the indigenous grasslands of southeastern South Island in relation to pre-human woody ecosystems  

Microsoft Academic Search

Immediately before human settlement, dense tall podocarp-angiosperm forest dominated the moist Southland and southern coastal Otago districts. Open, discontinuous podocarp-angiosperm forest bordered the central Otago dry interior, extending along the north Otago coast. Grassland was mostly patchy within these woody ecosystems, occurring on limited areas of droughty or low-nutrient soils and wetlands, or temporarily after infrequent fire or other disturbance.

M. S. McGlone

2001-01-01

310

Expression of host resistance to Salmonella typhi and Salmonella typhimurium: bacterial survival within macrophages of murine and human origin.  

PubMed

Cell-association of various strains of Salmonella typhi and Salmonella typhimurium with different populations of macrophages was studied. Macrophages were infected, exposed to gentamicin, washed, and counts of viable bacteria protected from gentamicin killing were made. J774A.1 cells, a continuous macrophage-like cell line, were the most permissive, all strains tested achieving similar high recoveries. Virulent S. typhimurium 779C-Sms, but not avirulent S. typhimurium 779C-SmD, survived well in mouse peritoneal macrophages and human monocyte-derived macrophages. Virulent S. typhi Ty2 were killed by mouse peritoneal macrophages, but were able to survive within human monocyte-derived macrophages. Viable counts of clinical isolates of S. typhi within the human monocyte-derived phagocytes were lower as compared with those of S. typhi Ty2. Phagocytosis of opsonized and non-opsonized virulent S. typhi Ty2 and S. typhimurium 779C-SmS by mouse peritoneal macrophages failed to trigger their respiratory burst as assessed by the intracellular reduction of nitroblue tetrazolium dye (NBT). These experiments support the view that the intracellular survival of Salmonella is in part host dependent and specific in nature. They also suggest that virulence influences the survival and intracellular multiplication of Salmonella within macrophages, and that their ultimate fate within macrophages may not be related to oxygen-dependent mechanisms. PMID:2190062

Vladoianu, I R; Chang, H R; Pechère, J C

1990-02-01

311

Expression of the human amylase genes: Recent origin of a salivary amylase promoter from an actin pseudogene  

SciTech Connect

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.

Samuelson, L.C.; Gumucio, D.L.; Meisler, M.H. (Univ. of Michigan, Ann Arbor (USA)); Wiebauer, K. (Friedrich Miescher Institut, Basel (Switzerland))

1988-09-12

312

Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis.  

PubMed

Evidence obtained from studies with yeast and Xenopus indicate that the initiation of DNA replication is a multistep process. The origin recognition complex (ORC), Cdc6p, and minichromosome maintenance (MCM) proteins are required for establishing prereplication complexes, upon which initiation is triggered by the activation of cyclin-dependent kinases and the Dbf4p-dependent kinase Cdc7p. The identification of human homologues of these replication proteins allows investigation of S-phase regulation in mammalian cells. Using centrifugal elutriation of several human cell lines, we demonstrate that whereas human Orc2 (hOrc2p) and hMcm proteins are present throughout the cell cycle, hCdc6p levels vary, being very low in early G(1) and accumulating until cells enter mitosis. hCdc6p can be polyubiquitinated in vivo, and it is stabilized by proteasome inhibitors. Similar to the case for hOrc2p, a significant fraction of hCdc6p is present on chromatin throughout the cell cycle, whereas hMcm proteins alternate between soluble and chromatin-bound forms. Loading of hMcm proteins onto chromatin occurs in late mitosis concomitant with the destruction of cyclin B, indicating that the mitotic kinase activity inhibits prereplication complex formation in human cells. PMID:11046155

Méndez, J; Stillman, B

2000-11-01

313

A glimpse into the early origins of medieval anatomy through the oldest conserved human dissection (Western Europe, 13th c. A.D.)  

PubMed Central

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.

Huynh-Charlier, Isabelle; Poupon, Joel; Lancelot, Eloise; Campos, Paula F.; Favier, Dominique; Jeannel, Gael-Francois; Bonati, Maurizio Rippa; de la Grandmaison, Geoffroy Lorin; Herve, Christian

2013-01-01

314

[Immunomodulators of microbial origin enhance cytotoxicity of human mononuclear leukocytes and reduce metastatic progression of Lewis lung carcinoma in mice].  

PubMed

Effect of immunomodulators for microbial origin on innate immunity and antitumor system was continued to study. Immunomodificator Immunovac VP-4, purified staphylococcal toxoid and glucosaminyl muramyl dipeptide (GMDP) equally enhanced cytotoxicity of mononuclear leukocytes of peripheral blood of healthy donors. Index of cytotoxicity was 2.78, 2.77 and 2.70 respectively. Reduced metastatic progression of Lewis lung carcinoma in mice was observed after Immunovac VP-4 and GMDP administration. Effectiveness was seen when preparations administered according to schedules including their administration before implantation of the tumor. If preparations were administered number of metastases reduced in 4.4-5.6 times and size of metastases reduced in 7-10 times. Interplay between antitumor activity of studied immunomodulators and cytotoxic activity of NK-cells, which are base effectors of antitumor immune response, are discussed. PMID:17163136

Akhmatova, N K; Semenova, I B; Donenko, F V; Kiselevski?, M V; Kurbatova, E A; Egorova, N B

2006-01-01

315

Evidence that the negative BOLD response is neuronal in origin: A simultaneous EEG-BOLD-CBF study in humans.  

PubMed

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 10s 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 8-13Hz 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

Mullinger, K J; Mayhew, S D; Bagshaw, A P; Bowtell, R; Francis, S T

2014-07-01

316

Human de novo papillary renal-cell carcinomas in a kidney graft: evidence of recipient origin with adenoma-carcinoma sequence.  

PubMed

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

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

317

Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of human imprinting and suggests a germline methylation-independent mechanism of establishment.  

PubMed

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

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

318

Characteristics of Mesenchymal Stem Cells Originating from the Bilateral Inferior Turbinate in Humans with Nasal Septal Deviation  

PubMed Central

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.

Choi, Jin; Lee, Dong Chang; Oh, Jeong Hoon; Kim, Sung Won; Kim, Jin Bae

2014-01-01

319

Topography of Gng2- and NetrinG2-Expression Suggests an Insular Origin of the Human Claustrum  

PubMed Central

The claustrum has been described in the forebrain of all mammals studied so far. It has been suggested that the claustrum plays a role in the integration of multisensory information: however, its detailed structure and function remain enigmatic. The human claustrum is a thin, irregular, sheet of grey matter located between the inner surface of the insular cortex and the outer surface of the putamen. Recently, the G-protein gamma2 subunit (Gng2) was proposed as a specific claustrum marker in the rat, and used to better delineate its anatomical boundaries and connections. Additional claustral markers proposed in mammals include Netrin-G2 in the monkey and latexin in the cat. Here we report the expression and distribution of Gng2 and Netrin-G2 in human post-mortem samples of the claustrum and adjacent structures. Gng2 immunoreactivity was detected in the neuropil of the claustrum and of the insular cortex but not in the putamen. A faint labelling was present also in the external and extreme capsules. Double-labelling experiments indicate that Gng2 is also expressed in glial cells. Netrin-G2 labelling was seen in neuronal cell bodies throughout the claustrum and the insular cortex but not in the medially adjacent putamen. No latexin immunoreactive element was detected in the claustrum or adjacent structures. Our results confirm that both the Gng2 and the Netrin-G2 proteins show an affinity to the claustrum and related formations also in the human brain. The presence of Gng2 and Netrin-G2 immunoreactive elements in the insular cortex, but not in the putamen, suggests a possible common ontogeny of the claustrum and insula.

Pirone, Andrea; Cozzi, Bruno; Edelstein, Larry; Peruffo, Antonella; Lenzi, Carla; Quilici, Francesca; Antonini, Rita; Castagna, Maura

2012-01-01

320

Origins of the High Catalytic Activity of Human Alcohol Dehydrogenase 4 Studied with Horse Liver A317C Alcohol Dehydrogenase  

PubMed Central

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 ? 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.

Herdendorf, Timothy J.; Plapp, Bryce V.

2011-01-01

321

Expression of PAX 3 alternatively spliced transcripts and identification of two new isoforms in human tumors of neural crest origin.  

PubMed

The developmental gene PAX 3 is expressed in the early embryo in developing muscle and elements of the nervous system, including the brain. Since no one has investigated the expression of the isoforms of PAX 3 in the neuroectodermal tumors melanoma and small cell lung cancer (SCLC), we have carried out a comprehensive screening for the expression of the isoforms PAX 3a-e using RT-PCR in human melanoma cell lines, primary human ocular and secondary cutaneous melanomas. We have identified 2 new isoforms of PAX 3, g and h, which we have isolated, cloned and sequenced. Sets of primers for each isoform were designed and their specificity was confirmed by sequence analysis of the products. The isoforms PAX 3a-e were detected in all human cutaneous melanoma cell lines (8/8), but only PAX 3c (1/2) and PAX 3d (2/2) in ocular melanoma cell lines. The same PAX 3 isoforms were detected in more than 80% of human cutaneous melanomas: PAX 3a and b (15/17), PAX 3c (14/17), PAX 3d (16/17) and PAX 3e (15/17). In contrast the results for 7 SCLC cell lines were PAX 3a (0/7), PAX 3b (1/7), PAX 3c (3/7), PAX 3d (6/7), PAX 3e (2/7); 8/8 cutaneous melanoma cell lines and 8/8 ocular melanoma tissues, together with 14/17 cutaneous melanoma tissues screened, expressed the new isoform PAX 3g. All 8 cutaneous melanoma cell lines expressed PAX 3h, but it was not detectable in any of the tumor tissues (0/20). Neither of the 2 ocular melanoma cell lines expressed the 2 new isoforms. Comparison of the different amplicon staining intensities on a gel suggests that PAX 3c and PAX 3d are the predominant transcripts expressed, with relatively low expression of PAX 3e and PAX 3h. We propose that these and the 2 new isoforms we have discovered may be important in oncogenesis and differential diagnosis of melanomas or SCLC. PMID:14639621

Parker, Craig J; Shawcross, Susan G; Li, Honggui; Wang, Qui-Yu; Herrington, C Simon; Kumar, Shant; MacKie, Rhona M; Prime, Wendy; Rennie, Ian G; Sisley, Karen; Kumar, Patricia

2004-01-10

322

Cumulative cultural evolution in the laboratory: An experimental approach to the origins of structure in human language  

PubMed Central

We introduce an experimental paradigm for studying the cumulative cultural evolution of language. In doing so we provide the first experimental validation for the idea that cultural transmission can lead to the appearance of design without a designer. Our experiments involve the iterated learning of artificial languages by human participants. We show that languages transmitted culturally evolve in such a way as to maximize their own transmissibility: over time, the languages in our experiments become easier to learn and increasingly structured. Furthermore, this structure emerges purely as a consequence of the transmission of language over generations, without any intentional design on the part of individual language learners. Previous computational and mathematical models suggest that iterated learning provides an explanation for the structure of human language and link particular aspects of linguistic structure with particular constraints acting on language during its transmission. The experimental work presented here shows that the predictions of these models, and models of cultural evolution more generally, can be tested in the laboratory.

Kirby, Simon; Cornish, Hannah; Smith, Kenny

2008-01-01

323

Immunoregulatory properties and LP-pattern of human ovarian carcinoma ascites and pleural effusions of nonmalignant origin.  

PubMed

The immunoregulatory activity of ascitic fluids obtained from patients with ovarian carcinoma, and pleural effusions collected from patients with various nonmalignant diseases, was tested. The following assays were performed: in vivo, PFC-response of mouse splenocytes to SRBC; in vitro, antibody-dependent cellular cytotoxicity (ADCC), and phagocytic activity of human peripheral blood mononuclear cells (PBMoC). The migration ability of mouse splenocytes in the presence of ascitic fluids was also evaluated. Parallelly, lipid (triglyceride and cholesterol) and lipoprotein (high-density/HDL/, low-density/LDL/, and very-low-density/VLDL/) content in ascites and pleural effusions, were determined. Both types of fluids suppressed the PFC-response and inhibited phagocytosis of 51Cr-labeled sheep erythrocytes by PBMoC, but augmented ADCC of PBMoC against sheep erythrocytes. An elevation of VLDL and a decrease of HDL and LDL in ascitic fluids and pleural effusions, as compared to normal human sera, were found. There were similar changes in the cholesterol content of these lipoprotein fractions, i.e., an increase of VLDL- and a decrease of HDL- and LDL-cholesterol. PMID:6612101

Marotti, T; Gabrilovac, J; Salzer, B; Krusi?, J

1983-01-01

324

Thermodynamic origins of protein folding, allostery, and capsid formation in the human hepatitis B virus core protein  

PubMed Central

HBc, the capsid-forming “core protein” of human hepatitis B virus (HBV), is a multidomain, ?-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, ?-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.

Alexander, Crispin G.; Jurgens, Maike C.; Shepherd, Dale A.; Freund, Stefan M. V.; Ashcroft, Alison E.; Ferguson, Neil

2013-01-01

325

Neanderthal Origin of the Haplotypes Carrying the Functional Variant Val92Met in the MC1R in Modern Humans.  

PubMed

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

Ding, Qiliang; Hu, Ya; Xu, Shuhua; Wang, Chuan-Chao; Li, Hui; Zhang, Ruyue; Yan, Shi; Wang, Jiucun; Jin, Li

2014-08-01

326

Shiga toxin glycosphingolipid receptor expression and toxin susceptibility of human pancreatic ductal adenocarcinomas of differing origin and differentiation.  

PubMed

Shiga toxins (Stxs) are composed of an enzymatically active A subunit (StxA) and a pentameric B subunit (StxB) that preferentially binds to the glycosphingolipid (GSL) globo\\xadtriaosylceramide (Gb3Cer/CD77) and to a reduced extent to globotetraosylceramide (Gb4Cer). The identification of Gb3Cer as a tumor-associated GSL in human pancreatic cancer prompted us to investigate the expression of Gb3Cer and Gb4Cer in 15 human pancreatic ductal adenocarcinoma cell lines derived from primary tumors and liver, ascites, and lymph node metastases. Thin-layer chromatography overlay assays revealed the occurrence of Gb3Cer in all and of Gb4Cer in the majority of cell lines, which largely correlated with transcriptional expression analysis of Gb3Cer and Gb4Cer synthases. Prominent Gb3Cer and Gb4Cer lipoform heterogeneity was based on ceramides carrying predominantly C16:0 and C24:0/C24:1 fatty acids. Stx2-mediated cell injury ranged from extremely high sensitivity (CD(50) of 0.94 pg/ml) to high refractiveness (CD(50) of 5.8 ?g/ml) and to virtual resistance portrayed by non-determinable CD(50) values even at the highest Stx2 concentration (10 ?g/ml) applied. Importantly, Stx2-mediated cytotoxicity did not correlate with Gb3Cer expression (the preferential Stx receptor), suggesting that the GSL receptor content does not primarily determine cell sensitivity and that other, yet to be delineated, cellular factors might influence the responsiveness of cancer cells. PMID:22944681

Storck, Wiebke; Meisen, Iris; Gianmoena, Kathrin; Pläger, Ina; Kouzel, Ivan U; Bielaszewska, Martina; Haier, Jörg; Mormann, Michael; Humpf, Hans-Ulrich; Karch, Helge; Müthing, Johannes

2012-08-01

327

Expression of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) in human urinary bladder transitional cell carcinoma.  

PubMed

The objective of this study was to evaluate the expression pattern of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) and its clinical significance in human bladder cancer (BC). We detected PBK/TOPK mRNA overexpression in BC and human normal testis tissues using RT-PCR. Using qRT-PCR revealed a higher expression of PBK/TOPK in BC tissues than their adjacent noncancerous tissues (ANCTs) (p<0.0001). Cytoplasmic expression of PBK/TOPK protein was found to be positive in 64.6% (42 of 65) BC patients. Expression of PBK/TOPK protein was found to be significantly higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC) (86.1% vs. 37.9%, p<0.001). The immunohistochemical (IHC) expression of PBK/TOPK was found to be significantly (p<0.001) associated with the stage of disease. Study findings suggest that the PBK/TOPK mRNA/protein expression is specific to human BC and might be used as a novel target for development of cancer immunotherapy and diagnostic biomarker. PMID:24629784

Singh, P K; Srivastava, Anupam K; Dalela, D; Rath, S K; Goel, M M; Bhatt, M L B

2014-06-01

328

Validation of an original incubator set-up for the exposure of human astrocyte cells to X-band microwaves in a GTEM-chamber.  

PubMed

A current concern about the biological effects of electromagnetic fields (EMF) is increasing with the wide spread use of X-band microwaves (MW, 8-10 GHz range). Gigahertz transverse electromagnetic (GTEM) field flat transmission lines are currently being used for experimental exposure of biological samples to high frequency EMF. Experiments carried out on human cells in culture require optimal growing temperature conditions, i.e. 37 °C, 5% CO2 in a humidified atmosphere. The aim of our work has been: i) to built up an original incubator set-up, the so called GTEM-incubator, for exposure of human cells in culture to MW inside a GTEM-chamber, under optimal growing physical conditions; ii) to make the validation of the GTEM-incubator by growing cell samples inside the non-energized GTEM-chamber (test sample) comparing the results with the ones obtained from cell samples grown inside a standard incubator (control samples). The features for comparison were: cell morphology, expression and distribution of cytoskeleton proteins, genotoxicity, viability and cell cycle progression. Any variation in any of the studied parameters would allow for detecting any possible failure or misconception in our GTEM-incubator working test. The results obtained in control and test incubators showed non-significant differences in the development of both cell populations for any of the studied parameters. Thereby our GTEM-incubator is considered valid for our purposes of human cell exposures to X-band MW. PMID:21751150

Pérez-Bruzón, R N; Del Moral, A; Pérez-Castejón, C; Llorente, M; Vera, A; Azanza, M J

2011-09-01

329

Identification of Novel Human Dipeptidyl Peptidase-IV Inhibitors of Natural Origin (Part II): In Silico Prediction in Antidiabetic Extracts  

PubMed Central

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.

Guasch, Laura; Sala, Esther; Ojeda, Maria Jose; Valls, Cristina; Blade, Cinta; Mulero, Miquel; Blay, Mayte; Ardevol, Anna; Garcia-Vallve, Santiago; Pujadas, Gerard

2012-01-01

330

Identification of Novel Human Dipeptidyl Peptidase-IV Inhibitors of Natural Origin (Part I): Virtual Screening and Activity Assays  

PubMed Central

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.

Guasch, Laura; Ojeda, Maria Jose; Gonzalez-Abuin, Noemi; Sala, Esther; Cereto-Massague, Adria; Mulero, Miquel; Valls, Cristina; Pinent, Montserrat; Ardevol, Anna; Garcia-Vallve, Santiago; Pujadas, Gerard

2012-01-01

331

Evidence for the evolutionary origin of human chromosome 21 from comparative gene mapping in the cow and mouse  

SciTech Connect

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.

Threadgill, D.S.; Womack, J.E. (Texas A and M Univ., College Station (United States)); Kraus, J.P. (Univ. of Colorado Health Sciences Center, Denver (United States)); Krawetz, S.A. (Wayne State Univ., Detroit, MI (United States))

1991-01-01

332

Malaria Parasite Sequences from Chimpanzee Support the Co-Speciation Hypothesis for the Origin of Virulent Human Malaria (Plasmodium falciparum)  

PubMed Central

Phylogenetic analyses of the mitochondrial cytochrome b (cytb), apicoplast caseinolytic protease C (clpC), and 18S rRNA sequences of Plasmodium isolates from chimpanzees along with those of the virulent human malaria parasite P. falciparum showed that the common chimpanzee (Pan troglodytes) malaria parasites, assigned by Rich et al. (2009; Proc. Natl. Acad. Sci. USA 106, 14902–14907) to P. reichenowi, constitute a paraphyletic assemblage. The assumption that P. falciparum diverged from P. reichenowi as recently as 5,000–50,000 years ago would require a rate of synonymous substitution/site/year in cytb and clpC on the order of 10?5–10?6, several orders of magnitude higher than any known from eukaryotic organelle genomes, and would imply an unrealistically recent timing of the most recent common ancestor of P. falciparum mitochondrial genomes. The available data are thus most consistent with the hypothesis that P. reichenowi (in the strict sense) and P. falciparum co-speciated with their hosts about 5–7 million years ago.

Hughes, Austin L.; Verra, Federica

2010-01-01

333

Structural Origins for the Loss of Catalytic Activities of Bifunctional Human LTA4H Revealed through Molecular Dynamics Simulations  

PubMed Central

Human leukotriene A4 hydrolase (hLTA4H), which is the final and rate-limiting enzyme of arachidonic acid pathway, converts the unstable epoxide LTA4 to a proinflammatory lipid mediator LTB4 through its hydrolase function. The LTA4H is a bi-functional enzyme that also exhibits aminopeptidase activity with a preference over arginyl tripeptides. Various mutations including E271Q, R563A, and K565A have completely or partially abolished both the functions of this enzyme. The crystal structures with these mutations have not shown any structural changes to address the loss of functions. Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in catalytic functions. The observed protein-ligand hydrogen bonds and distances between the important catalytic components have correlated well with the experimental results. This study also confirms based on the structural observation that E271 is very important for both the functions as it holds the catalytic metal ion at its location for the catalysis and it also acts as N-terminal recognition residue during peptide binding. The comparison of binding modes of substrates revealed the structural changes explaining the importance of R563 and K565 residues and the required alignment of substrate at the active site. The results of this study provide valuable information to be utilized in designing potent hLTA4H inhibitors as anti-inflammatory agents.

Thangapandian, Sundarapandian; John, Shalini; Lazar, Prettina; Choi, Sun; Lee, Keun Woo

2012-01-01

334

Compartmentalized Human Immunodeficiency Virus Type 1 Originates from Long-Lived Cells in Some Subjects with HIV-1-Associated Dementia  

PubMed Central

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1–associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1–associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t1/2 mean?=?2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t1/2 range?=?9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W.; Swanstrom, Ronald

2009-01-01

335

Influence of Oxygen Tension on Dopaminergic Differentiation of Human Fetal Stem Cells of Midbrain and Forebrain Origin  

PubMed Central

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 ?-tubulin III and GFAP expression in both cultures. Up-regulation of ?-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.

Krabbe, Christina; Bak, Sara Thornby; Jensen, Pia; von Linstow, Christian; Martinez Serrano, Alberto; Hansen, Claus; Meyer, Morten

2014-01-01

336

KRAS2 Mutations in Human Pancreatic Acinar-Ductal Metaplastic Lesions are Limited to those with PanIN: Implications for the Human Pancreatic Cancer Cell of Origin  

PubMed Central

Background Pancreatic intraepithelial neoplasia (PanIN) is a precursor to invasive ductal adenocarcinoma of the pancreas. Observations made in genetically engineered mouse models suggest that the acinar/centroacinar compartment can give rise to ductal neoplasia. In order to integrate findings in mice and men, we examined human acinar cells, acinar-ductal metaplasia (ADM) lesions and PanINs for KRAS2 gene mutations. Methods Surgically resected pancreata were screened for foci of ADM with or without an associated PanIN lesion. Stromal cells, acinar cells, ADMs, and PanINs, were separately isolated using laser capture microdissection. KRAS2 status was analyzed using genomic DNA isolated from the microdissected tissue. Results Twelve of these 31 foci of ADM occurred in isolation, while 19 were in the same lobules as a PanIN lesion. All 31 microdissected foci of acinar cells were KRAS2 gene wild-type, as were all 12 isolated ADM lesions lacking an associated PanIN. KRAS2 gene mutations were present in 14 of 19 (74%) PanIN lesions, and in 12 of the 19 (63%) foci of ADM associated with these PanINs. All ADM lesions with a KRAS2 gene mutation harbored the identical KRAS2 gene mutation found in their associated PanIN lesions. Conclusions Ductal neoplasms of the human pancreas, as defined by KRAS2 gene mutations, do not appear to arise from acinar cells. Isolated AMD lesions are genetically distinct from those associated with PanINs, and the latter may represent retrograde extension of the neoplastic PanIN cells, or less likely are PanIN precursor lesions.

Shi, Chanjuan; Hong, Seung-Mo; Lim, Phillip; Kamiyama, Hirohiko; Khan, Mehtab; Anders, Robert A.; Goggins, Michael; Hruban, Ralph H.

2009-01-01

337

Use of an autonomous parvovirus vector for selective transfer of a foreign gene into transformed human cells of different tissue origins and its expression therein.  

PubMed Central

In this work, we report the transduction of a chloramphenicol acetyltransferase (CAT) reporter gene into a variety of normal and transformed human cells of various tissue origins. The vector used was MVM/P38cat, a recombinant of the prototype strain of the autonomous parvovirus minute virus of mice (MVMp). The CAT gene was inserted into the capsid-encoding region of the infectious molecular clone of MVMp genome, under the control of the MVM P38 promoter. When used to transfect permissive cells, the MVM/P38cat DNA was efficiently replicated and expressed the foreign CAT gene at high levels. By cotransfecting with a helper plasmid expressing the capsid proteins, it was possible to produce mixed virus stocks containing MVM/P38cat infectious particles and variable amounts of recombinant MVM. MVM/P38cat viral particles were successfully used to transfer the CAT gene and to express it in a variety of human cells. Both viral DNA replication and P38-driven CAT expression were achieved in fibroblasts, epithelial cells, T lymphocytes, and macrophages in a transformation-dependent way, but with an efficiency depending on the cell type. In transformed B lymphocytes, however, the vector was not replicated, nor did it express the CAT gene. Images

Dupont, F; Tenenbaum, L; Guo, L P; Spegelaere, P; Zeicher, M; Rommelaere, J

1994-01-01

338

Genetic and molecular characterization of the human osteosarcoma 3AB-OS cancer stem cell line: a possible model for studying osteosarcoma origin and stemness.  

PubMed

Finding new treatments targeting cancer stem cells (CSCs) within a tumor seems to be critical to halt cancer and improve patient survival. Osteosarcoma is an aggressive tumor affecting adolescents, for which there is no second-line chemotherapy. Uncovering new molecular mechanisms underlying the development of osteosarcoma and origin of CSCs is crucial to identify new possible therapeutic strategies. Here, we aimed to characterize genetically and molecularly the human osteosarcoma 3AB-OS CSC line, previously selected from MG63 cells and which proved to have both in vitro and in vivo features of CSCs. Classic cytogenetic studies demonstrated that 3AB-OS cells have hypertriploid karyotype with 71-82 chromosomes. By comparing 3AB-OS CSCs to the parental cells, array CGH, Affymetrix microarray, and TaqMan® Human MicroRNA array analyses identified 49 copy number variations (CNV), 3,512 dysregulated genes and 189 differentially expressed miRNAs. Some of the chromosomal abnormalities and mRNA/miRNA expression profiles appeared to be congruent with those reported in human osteosarcomas. Bioinformatic analyses selected 196 genes and 46 anticorrelated miRNAs involved in carcinogenesis and stemness. For the first time, a predictive network is also described for two miRNA family (let-7/98 and miR-29a,b,c) and their anticorrelated mRNAs (MSTN, CCND2, Lin28B, MEST, HMGA2, and GHR), which may represent new biomarkers for osteosarcoma and may pave the way for the identification of new potential therapeutic targets. PMID:23129384

Di Fiore, Riccardo; Fanale, Daniele; Drago-Ferrante, Rosa; Chiaradonna, Ferdinando; Giuliano, Michela; De Blasio, Anna; Amodeo, Valeria; Corsini, Lidia R; Bazan, Viviana; Tesoriere, Giovanni; Vento, Renza; Russo, Antonio

2013-06-01

339

NOVA: Origins  

NSDL National Science Digital Library

At NOVA's Origins website, users can "journey back to the beginning of everything: the universe, Earth, and life itself." The web site offers a series of interactive modules where visitors can decide if life exists on other planets in the Milky Way, view where scientists are making large discoveries of life's origins, and much more. Users can find fascinating articles addressing life on Mars, the necessity of water for life, and the role galaxies play in our existence. Educators should soon be able to find a Teacher's Guide for the PBS television program airing in September.

340

Modern Humans Did Not Admix with Neanderthals during Their Range Expansion into Europe  

Microsoft Academic Search

The process by which the Neanderthals were replaced by modern humans between 42,000 and 30,000 before present is still intriguing. Although no Neanderthal mitochondrial DNA (mtDNA) lineage is found to date among several thousands of Europeans and in seven early modern Europeans, interbreeding rates as high as 25% could not be excluded between the two subspecies. In this study, we

Mathias Currat; Laurent Excoffier

2004-01-01

341

Patterns of Ancestral Human Diversity: An Analysis of Alu-Insertion and Restriction-Site Polymorphisms  

PubMed Central

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.

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

342

DNA Replication of Human Papillomavirus Type 31 Is Modulated by Elements of the Upstream Regulatory Region That Lie 5? of the Minimal Origin  

PubMed Central

The viral replication factors E1 and E2 of papillomaviruses are necessary and sufficient to replicate plasmids containing the minimal origin of DNA replication in transient assays. Under physiological conditions, the upstream regulatory region (URR) governs expression of the early viral genes. To determine the effect of URR elements on E1 and E2 expression specifically, and on the regulation of DNA replication during the various phases of the viral life cycle, we carried out a systematic replication study with entire genomes of human papillomavirus type 31 (HPV31), a high-risk oncogenic type. We constructed a series of URR deletions, spacer replacements, and point mutations to analyze the role of the keratinocyte enhancer (KE) element, the auxiliary enhancer (AE) domain, and the L1-proximal end of the URR (5?-URR domain) in DNA replication during establishment, maintenance, and vegetative viral DNA amplification. Using transient and stable replication assays, we demonstrate that the KE and AE are necessary for efficient E1 and E2 gene expression and that the KE can also directly modulate viral replication. KE-mediated activation of replication is dependent on the position and orientation of the element. Mutation of either one of the four Ap1 sites, the single Sp1 site, or the binding site for the uncharacterized footprint factor 1 reduced replication efficiency through decreased expression of E1 and E2. Furthermore, the 5?-URR domain and the Oct1 DNA binding site are dispensable for viral replication, since such HPV31 mutants are able to replicate efficiently in a transient assay, maintain a stable copy number over several cell generations, and amplify viral DNA under vegetative conditions. Interestingly, deletion of the 5?-URR domain leads to increased transient and stable replication levels. These findings suggest that elements in the HPV31 URR outside the minimal origin modulate viral replication through both direct and indirect mechanisms.

Hubert, Walter G.; Kanaya, Taro; Laimins, Laimonis A.

1999-01-01

343

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

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.

Brunk, U.T. (Linkoeping Univ. (Sweden))

1989-01-01

344

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

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.

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

345

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.  

PubMed

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. PMID:2486159

Brunk, U T

1989-01-01

346

Synchronous Chorusing and Human Origins  

Microsoft Academic Search

Evenly paced time marking in measured music allows us to predict where the next beat is going to fall. This makes musical pulse a cardinal device for coordinating the behavior of several individuals in a joint, coherent, synchronized performance. Such behavioral synchrony to a regular beat on the part of many individuals is rare among higher animals and raises the

Björn Merker

347

Parental Effect of DNA (Cytosine-5) Methyltransferase 1 on Grandparental-Origin-Dependent Transmission Ratio Distortion in Mouse Crosses and Human Families  

PubMed Central

Transmission ratio distortion (TRD) is a deviation from the expected Mendelian 1:1 ratio of alleles transmitted from parents to offspring and may arise by different mechanisms. Earlier we described a grandparental-origin-dependent sex-of-offspring-specific TRD of maternal chromosome 12 alleles closely linked to an imprinted region and hypothesized that it resulted from imprint resetting errors in the maternal germline. Here, we report that the genotype of the parents for loss-of-function mutations in the Dnmt1 gene influences the transmission of grandparental chromosome 12 alleles. More specifically, maternal Dnmt1 mutations restore Mendelian transmission ratios of chromosome 12 alleles. Transmission of maternal alleles depends upon the presence of the Dnmt1 mutation in the mother rather than upon the Dnmt1 genotype of the offspring. Paternal transmission mirrors the maternal one: live-born offspring of wild-type fathers display 1:1 transmission ratios, whereas offspring of heterozygous Dnmt1 mutant fathers tend to inherit grandpaternal alleles. Analysis of allelic transmission in the homologous region of human chromosome 14q32 detected preferential transmission of alleles from the paternal grandfather to grandsons. Thus, parental Dnmt1 is a modifier of transmission of alleles at an unlinked chromosomal region and perhaps has a role in the genesis of TRD.

Yang, Lanjian; Andrade, Moises Freitas; Labialle, Stephane; Moussette, Sanny; Geneau, Genevieve; Sinnett, Donna; Belisle, Alexandre; Greenwood, Celia M. T.; Naumova, Anna K.

2008-01-01

348

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

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.

Christodoulou, I.; Kolisis, F. N.; Papaevangeliou, D.; Zoumpourlis, V.

2013-01-01

349

Return of the metabolic trajectory to the original area after human bone marrow mesenchymal stem cell transplantation for the treatment of fulminant hepatic failure.  

PubMed

Our recent study first demonstrated that human bone marrow mesenchymal stem cell (hBMSC) transplantation could prevent death from fulminant hepatic failure (FHF) in pigs. To further clarify the metabolic mechanism of hBMSC transplantation in FHF, the plasma collected from FHF pigs that received transplantation of hBMSCs was examined using metabolic analysis to identify the key molecular markers that regulate recovery. The results showed that obvious metabolic disturbance occurred during FHF, whereas the hBMSC transplantation group showed less severe liver injury. The metabolic trajectory returns to its original state at week 3 following the hBMSC transplantation. In total, the concentration of 26 metabolites, including conjugated bile acids, phosphatidylcholines, lysophosphatidylcholines, fatty acids, amino acid and sphingomyelin, are significantly different between the FHF group and the hBMSC transplantation group. Moreover, the time course of changes in the metabolites corresponded with that of the biochemical and histological analyses. Real-time PCR further confirmed that the gene expression of phospholipase A1, lecithin-cholesterol acyltransferase and lysophosphatidylcholine acyltransferase 1 decreased significantly, whereas that of phospholipase A2 remained stable, which explains the decrease of the phosphatidylcholines and lysophosphatidylcholines. These novel results have revealed a metabolic mechanism for the hBMSC transplantation in FHF, which could lead to the future development of treatment strategies for stem cell therapies. PMID:22582960

Li, Jun; Xin, Jiaojiao; Hao, Shaorui; Zhang, Liyuan; Jiang, Longyan; Chen, Deying; Xie, Qing; Xu, Wei; Cao, Hongcui; Li, Lanjuan

2012-06-01

350

[Elimination from the digestive tract of a "gnotoxenic" child of a "Lactobacillus casei" strain, isolated from a commercial preparation: antagonistic effect of an "Escherichia coli" strain of human origin, demonstrated in "gnotoxenic" mice (author's transl)].  

PubMed

A strain of Lactobacillus casei from a pharmaceutical preparation became established in the digestive tract of an axenic child. It was eliminated by the first bacteria occurring after inoculation of the child's digestive tract with a human flora, before the child was taken out of the isolator. Using "gnotoxenic" mice, we found that the elimination of L. casei was due to a bactericidal effect of the Escherichia coli of human origin, within the digestive tract. PMID:828463

Hudault, S; Ducluzeau, R; Dubos, F; Raibaud, P; Ghnassia, J C; Griscelli, C

1976-07-01

351

Prevalence and characterization of Salmonella infantis isolates originating from different points of the broiler chicken-human food chain in Hungary.  

PubMed

During the 10-month study period Salmonella contamination of broiler houses and the flocks reared in three farms (A, B and C), the slaughter houses where the flocks were slaughtered, as well as the carcass and retail raw meat products originating from them was investigated. In the broiler farm A five consecutive flocks, in the B and C farms one flock was sampled. Environmental samples were taken prior to the introductions. Environmental, drinking water, feed and faecal samples were collected regularly using standard methods. Before and during processing of the flocks, environmental and carcass samples were taken at the abattoirs. Salmonella contamination of the carcass, retail meat, as well as stool samples of farm and abattoir workers and from human illnesses registered in the same period and region were also examined. Isolation, sero-, phage- and antibiotic resistance typing, class 1 integron and plasmid profiling of the strains were performed; their genetic relationship was assessed by PFGE. Although the broiler house and the faecal samples of the 5 flocks of the farm A were negative for Salmonella, S. infantis was isolated from 20-100% of the abattoir carcass samples. The retail raw meat samples were 0-100% S. infantis positive. The environmental samples of farm B were Salmonella negative, but the examined flock was contaminated: S. infantis was identified from 43% of the faecal samples. This serotype was identified in 100% of the carcass and retail raw meat samples. From environmental samples taken before the arrival of the 1-day-old chicks in the broiler house C, S. infantis was cultured. S. infantis prevalence in the faecal samples was 35% and all the carcass and retail raw meat samples were S. infantis contaminated. Altogether 164 S. infantis strains were isolated out of which 145 were further characterized. The vast majority (142/145) of the strains belonged to phage types 217 and 213. All but one were characterized by the nalidixic acid-streptomycin-sulphonamide-tetracycline resistances, had an 885 bp class 1 integron and a large plasmid of > 168 kb in size. The strains showed > or = 88.7% genetic similarity. The results obtained shows that the same multi-drug resistant S. infantis clone was spread from the examined broiler farms contaminating the slaughter and the retail meat and appeared in the human illnesses of the examined region that was earlier detected as the dominant clone characteristic of the broiler and human population of the whole country. PMID:18707787

Nógrády, N; Kardos, G; Bistyák, A; Turcsányi, I; Mészáros, J; Galántai, Zs; Juhász, A; Samu, P; Kaszanyitzky, J E; Pászti, J; Kiss, I

2008-09-30

352

Back to the Origin  

PubMed Central

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.

Evertts, Adam G.

2012-01-01

353

Extraintestinal pathogenic Escherichia coli O1:K1:H7/NM from human and avian origin: detection of clonal groups B2 ST95 and D ST59 with different host distribution  

PubMed Central

Background Extraintestinal pathogenic Escherichia coli (ExPEC) strains of serotype O1:K1:H7/NM are frequently implicated in neonatal meningitis, urinary tract infections and septicemia in humans. They are also commonly isolated from colibacillosis in poultry. Studies to determine the similarities of ExPEC from different origins have indicated that avian strains potentially have zoonotic properties. Results A total of 59 ExPEC O1:K1:H7/NM isolates (21 from avian colibacillosis, 15 from human meningitis, and 23 from human urinary tract infection and septicemia) originated from four countries were characterized by phylogenetic PCR grouping, Multilocus Sequence Typing (MLST), Pulsed Field Gel Electrophoresis (PFGE) and genotyping based on several genes known for their association with ExPEC or avian pathogenic Escherichia coli (APEC) virulence. APEC and human ExPEC isolates differed significantly in their assignments to phylogenetic groups, being phylogroup B2 more prevalent among APEC than among human ExPEC (95% vs. 53%, P = 0.001), whereas phylogroup D was almost exclusively associated with human ExPEC (47% vs. 5%, P = 0.0000). Seven virulence genes showed significant differences, being fimAvMT78 and sat genes linked to human isolates, while papGII, tsh, iron, cvaC and iss were significantly associated to APEC. By MLST, 39 of 40 ExPEC belonging to phylogroup B2, and 17 of 19 belonging to phylogroup D exhibited the Sequence Types (STs) ST95 and ST59, respectively. Additionally, two novel STs (ST1013 and ST1006) were established. Considering strains sharing the same ST, phylogenetic group, virulence genotype and PFGE cluster to belong to the same subclone, five subclones were detected; one of those grouped six strains of human and animal origin from two countries. Conclusion Present results reveal that the clonal group B2 O1:K1:H7/NM ST95, detected in strains of animal and human origin, recovered from different dates and geographic sources, provides evidence that some APEC isolates may act as potential pathogens for humans and, consequently, poultry as a foodborne source, suggesting no host specificity for this type of isolates. A novel and important finding has been the detection of the clonal group D O1:K1:H7/NM ST59 almost exclusively in humans, carrying pathogenic genes linked to the phylogenetic group D. This finding would suggest D O1:K1:H7/NM ST59 as a host specific pathotype for humans.

2009-01-01

354

The Origin of Homo  

Microsoft Academic Search

Despite a steady increase in the number and diversity of African Middle Pliocene hominin fossils, paleoanthropolo-gists are\\u000a not now substantially closer to understanding the temporal, geographical or ecological contexts of the origin of the Homo clade than was the case in 1964, when Louis Leakey, Phillip Tobias and John Napier introduced Homo habilis as the earliest species of the human

William H. Kimbel

355

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

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.

Torres, Montserrat; Gonzalez, Cristina; del Romero, Jorge; Viciana, Pompeyo; Ocampo, Antonio; Rodriguez-Fortunez, Patricia; Masia, Mar; Blanco, Jose Ramon; Portilla, Joaquin; Rodriguez, Carmen; Hernandez-Novoa, Beatriz; del Amo, Julia

2013-01-01

356

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

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

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

357

Late Pleistocene adult mortality patterns and modern human establishment  

PubMed Central

The establishment of modern humans in the Late Pleistocene, subsequent to their emergence in eastern Africa, is likely to have involved substantial population increases, during their initial dispersal across southern Asia and their subsequent expansions throughout Africa and into more northern Eurasia. An assessment of younger (20–40 y) versus older (>40 y) adult mortality distributions for late archaic humans (principally Neandertals) and two samples of early modern humans (Middle Paleolithic and earlier Upper Paleolithic) provides little difference across the samples. All three Late Pleistocene samples have a dearth of older individuals compared with Holocene ethnographic/historical samples. They also lack older adults compared with Holocene paleodemographic profiles that have been critiqued for having too few older individuals for subsistence, social, and demographic viability. Although biased, probably through a combination of preservation, age assessment, and especially Pleistocene mobility requirements, these adult mortality distributions suggest low life expectancy and demographic instability across these Late Pleistocene human groups. They indicate only subtle and paleontologically invisible changes in human paleodemographics with the establishment of modern humans; they provide no support for a life history advantage among early modern humans.

Trinkaus, Erik

2011-01-01

358

Late Pleistocene adult mortality patterns and modern human establishment.  

PubMed

The establishment of modern humans in the Late Pleistocene, subsequent to their emergence in eastern Africa, is likely to have involved substantial population increases, during their initial dispersal across southern Asia and their subsequent expansions throughout Africa and into more northern Eurasia. An assessment of younger (20-40 y) versus older (>40 y) adult mortality distributions for late archaic humans (principally Neandertals) and two samples of early modern humans (Middle Paleolithic and earlier Upper Paleolithic) provides little difference across the samples. All three Late Pleistocene samples have a dearth of older individuals compared with Holocene ethnographic/historical samples. They also lack older adults compared with Holocene paleodemographic profiles that have been critiqued for having too few older individuals for subsistence, social, and demographic viability. Although biased, probably through a combination of preservation, age assessment, and especially Pleistocene mobility requirements, these adult mortality distributions suggest low life expectancy and demographic instability across these Late Pleistocene human groups. They indicate only subtle and paleontologically invisible changes in human paleodemographics with the establishment of modern humans; they provide no support for a life history advantage among early modern humans. PMID:21220336

Trinkaus, Erik

2011-01-25

359

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

Nine staphylococcal strains of human and animal origin with a lincomycin-resistant/erythromycin-susceptible phenotype and carrying vga genes were characterised to determine the genetic elements involved in the dissemination of these uncommon resistance genes. These strains were typed by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) and/or spa typing. Antimicrobial susceptibility was studied by disk diffusion and agar dilution methods. Presence of the genes lnu(A), lnu(B), vga(A), vga(A)v, vga(B), vga(C), vga(E), lsa(B) and cfr was studied by PCR. Transformation experiments were carried out in all strains, and the plasmid or chromosomal gene location was determined by Southern blot analysis. Genetic environments of the vga genes were analysed by PCR mapping or inverse PCR and sequencing. Five meticillin-resistant Staphylococcus aureus (MRSA) ST398 strains and three Staphylococcus epidermidis strains harboured the gene vga(A), and one MRSA-ST8 strain contained the gene vga(A)v. One MRSA-ST398 strain, which also contained the gene lnu(A), showed the highest minimum inhibitory concentration (MIC) to lincomycin. The vga(A)v-positive strain presented lower MIC values than the vga(A)-positive strains. Presence of the pVGA plasmid was confirmed in two MRSA-ST398 strains. Four novel vga(A)-carrying plasmids were detected: pUR2355 (in two MRSA and one meticillin-susceptible S. epidermidis); pUR4128 (one MRSA); pUR3036 [one meticillin-resistant S. epidermidis (MRSE)]; and pUR3937 (one MRSE). The plasmid pUR4128 was very similar to pUR2355. Plasmids pUR3036 and pUR3937 were related and were very similar to plasmid pSE-12228-06. The gene vga(A)v was located in a transposon analogous to Tn5406. Therefore, four novel vga(A)-carrying plasmids and a variant of Tn5406 were identified in this study. PMID:22901706

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

360

Poetry or pathology? Jesuit hypochondria in early modern Naples.  

PubMed

In their didactic poems on fishing and chocolate, both published in 1689, two Neapolitan Jesuits digressed to record and lament a devastating 'plague' of 'hypochondria'. The poetic plagues of Niccolò Giannettasio and Tommaso Strozzi have literary precedents in Lucretius, Vergil, and Fracastoro, but it will be argued that they also have a real, contemporary significance. Hypochondria was considered to be a serious (and epidemic) illness in the seventeenth century, with symptoms ranging from depression to delusions. Not only did our Jesuit poets claim to have suffered from it, but so did prominent members of the 'Accademia degl'Investiganti', a scientific society in Naples that was at odds with both the religious and medical establishments. PMID:18173170

Haskell, Yasmin

2007-01-01

361

Astronomical exegesis. An early modern Jewish interpretation of the heavens  

NASA Astrophysics Data System (ADS)

Contents: David Gans (1541-1613) and the cosmological systems. Reasons for the multiplicity of cosmologies. Social goals. Rhetorical convention. Theological influences. The influence of traditional study practices.

Efron, Noah J.; Fisch, Menachem

362

Shutt up: bubonic plague and quarantine in early modern England.  

PubMed

The outbreak of bubonic plague that struck London and Westminster in 1636 provoked the usual frenzied response to epidemics, including popular flight and government-mandated quarantine. The government asserted that plague control measures were acts of public health for the benefit of all. However, contrary to this government narrative of disease prevention there was a popular account that portrayed quarantine and isolation as personal punishment rather than prudent policy. In examining the 1636 outbreak on the parish as well as the individual level, reasons for this inconsistency between official and unofficial perspectives emerge. Quarantine and its effects were not classless, and its implementation was not always strictly in the name of public health. Government application of quarantine was remarkably effective, but it could never be uncontroversial both because of circumstances and because of misuse. The flight of the wealthiest from London and Westminster left only the more socially vulnerable to be quarantined. Though plague policy was financially sensitive to the poorest, it was costly to the middling sort. Another cause of controversy was the government's use of quarantine as a punishment to control individuals found breaking other laws. Though not widely publicized, popular narratives continually included grievances about the cruelty and inequity of quarantine and the militaristic nature of its implementation. Despite these objections, quarantine remained a staple of the government response to plague outbreaks throughout the seventeenth century. PMID:22611587

Newman, Kira L S

2012-01-01

363

Introduction: experimenting with animals in the early modern era.  

PubMed

The aim of this special issue is to address issues surrounding the use of live animals in experimental procedures in the pre-modern era, with a special emphasis on the technical, anatomical, and philosophical sides. Such use raises philosophical, scientific, and ethical questions about the nature of life, the reliability of the knowledge acquired, and animal suffering. PMID:23011046

Guerrini, Anita; Meli, Domenico Bertoloni

2013-01-01

364

Chemical and mechanical theories of digestion in early modern medicine.  

PubMed

The aim of this paper is to survey the iatrochemists' and iatromechanists' explanations of digestion, from the sixteenth to the early decades of the eighteenth century. The iatrochemists substituted the Galenic thermal digestion with a series of chemical processes, the same as those produced in the laboratory. Jean Baptiste van Helmont marked a turning point in the chemical understanding of digestion, indicating the acid ferment in the stomach as the digestive agent. In the wake of van Helmont, an increasing number of physicians rejected the traditional Galenic theory of digestion, turning to the chemical reactions taking place in the ventricles. The iatrochemists saw nutrition as the outcome of the separation of an active invisible substance, i.e., spirits, from a thick inert covering. The emergence of the mechanical physiology, with its emphasis on the shape, size and motion of parts, did not bring about a decline of the chemical investigations of digestion. Descartes ruled out chemistry in the study of physiology, while a number of physiologists-notably in England-adopted a compromise between iatrochemical and mechanical theories. In the second half of the seventeenth century, the view of acid as an agent of gastric digestion became popular among physiologists. Late in the century, the acid-alkali doctrine spurred further investigations on digestion and nutrition. PMID:22520182

Clericuzio, Antonio

2012-06-01

365

Gender and the Social Order in Early Modern England.  

ERIC Educational Resources Information Center

The place of the family and the relationship between gender and social order in England between 1560 and 1725 are examined. The fear of disorder so prevalent in England in the late 16th and early 17th centuries was caused by the doubling of the population and extremely poor economic conditions. In the attempt to enforce order, the analogy between…

Amussen, Susan Dwyer

366

Medical Examination and Poor Relief in Early Modern Germany  

PubMed Central

Summary This article investigates the role of the medical examination in municipal poor relief programmes between 1570 and 1620. Documents from the city of Nördlingen, a community of approximately 10,000 people in 1600, suggest that municipal facilities addressed a range of serious illnesses for a wide spectrum of the population. Practitioners were influenced by their Galenic medical milieu but ultimately focused on a range of practical resource questions rather than the diagnosis of an individual's disease.

Hammond, Mitchell Lewis

2011-01-01

367

Mutational Profiling of Kinases in Human Tumours of Pancreatic Origin Identifies Candidate Cancer Genes in Ductal and Ampulla of Vater Carcinomas  

Microsoft Academic Search

BackgroundProtein kinases are key regulators of cellular processes (such as proliferation, apoptosis and invasion) that are often deregulated in human cancers. Accordingly, kinase genes have been the first to be systematically analyzed in human tumors leading to the discovery that many oncogenes correspond to mutated kinases. In most cases the genetic alterations translate in constitutively active kinase proteins, which are

Vincenzo Corbo; Rossana Ritelli; Stefano Barbi; Niccola Funel; Daniela Campani; Alberto Bardelli; Aldo Scarpa; Hana Algül

2010-01-01

368

Psychrobacter isolates of human origin, other than Psychrobacter phenylpyruvicus, are predominantly Psychrobacter faecalis and Psychrobacter pulmonis, with emended description of P. faecalis.  

PubMed

Human Psychrobacter isolates, other than Psychrobacter phenylpyruvicus, are predominantly designated Psychrobacter immobilis. Phenotypic and genotypic testing of Psychrobacter isolates that have been deposited in different culture collections as P. immobilis indicates that most of these human isolates belong to the species Psychrobacter faecalis and Psychrobacter pulmonis. PMID:21551328

Deschaght, Pieter; Janssens, Michèle; Vaneechoutte, Mario; Wauters, Georges

2012-03-01

369

The Origins of Options  

PubMed Central

Most research on decision making has focused on how human or animal decision makers choose between two or more options, posed in advance by the researchers. The mechanisms by which options are generated for most decisions, however, are not well understood. Models of sequential search have examined the trade-off between continued exploration and choosing one’s current best option, but still cannot explain the processes by which new options are generated. We argue that understanding the origins of options is a crucial but untapped area for decision making research. We explore a number of factors which influence the generation of options, which fall broadly into two categories: psycho-biological and socio-cultural. The former category includes factors such as perceptual biases and associative memory networks. The latter category relies on the incredible human capacity for culture and social learning, which doubtless shape not only our choices but the options available for choice. Our intention is to start a discussion that brings us closer toward understanding the origins of options.

Smaldino, Paul E.; Richerson, Peter J.

2012-01-01

370

First Case of Pulmonary Disease Caused by a Mycobacterium avium Complex Strain of Presumed Veterinary Origin in an Adult Human Patient  

PubMed Central

We report the first case of pulmonary disease caused by a strain of Mycobacterium avium complex of presumed veterinary origin in an elderly patient. All serial isolates were identified by multilocus sequence analysis based on rpoB, hsp65, and 16S rRNA fragments. Disease persisted despite macrolide-based combination antibiotic therapy.

Kim, Su-Young; Shin, Sung Jae; Lee, Nam Yong

2013-01-01

371

First case of pulmonary disease caused by a Mycobacterium avium complex strain of presumed veterinary origin in an adult human patient.  

PubMed

We report the first case of pulmonary disease caused by a strain of Mycobacterium avium complex of presumed veterinary origin in an elderly patient. All serial isolates were identified by multilocus sequence analysis based on rpoB, hsp65, and 16S rRNA fragments. Disease persisted despite macrolide-based combination antibiotic therapy. PMID:23554206

Kim, Su-Young; Shin, Sung Jae; Lee, Nam Yong; Koh, Won-Jung

2013-06-01

372

Multilocus sequence typing, pulsed-field gel electrophoresis, and fla short variable region typing of clonal complexes of Campylobacter jejuni strains of human, bovine, and poultry origins in Luxembourg.  

PubMed

Campylobacter jejuni is the most common cause of bacterial gastroenteritis in Luxembourg, with a marked seasonal peak during summer. The majority of these infections are thought to be sporadic, and the relative contribution of potential sources and reservoirs is still poorly understood. We monitored human cases from June to September 2006 (n = 124) by molecular characterization of isolates with the aim of rapidly detecting temporally related cases. In addition, isolates from poultry meat (n = 36) and cattle cecal contents (n = 48) were genotyped for comparison and identification of common clusters between veterinary and human C. jejuni populations. A total of 208 isolates were typed by sequencing the fla short variable region, macrorestriction analysis resolved by pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). We observed a high diversity of human strains during a given summer season. Poultry and human isolates had a higher diversity of sequence types than isolates of bovine origin, for which clonal complexes CC21 (41.6%) and CC61 (18.7%) were predominant. CC21 was also the most common complex found among human isolates (21.8%). The substantial concordance between PFGE and MLST results for this last group of strains suggests that they are clonally related. Our study indicates that while poultry remains an important source, cattle could be an underestimated reservoir of human C. jejuni cases. Transmission mechanisms of cattle-specific strains warrant further investigation. PMID:18931296

Ragimbeau, Catherine; Schneider, François; Losch, Serge; Even, Jos; Mossong, Joël

2008-12-01

373

Whole-Genome Analysis of a Rare Human Korean G3P[9] Rotavirus Strain Suggests a Complex Evolutionary Origin Potentially Involving Reassortment Events between Feline and Bovine Rotaviruses  

PubMed Central

A rare human rotavirus, G3P[9] strain RVA/Human-tc/KOR/CAU12-2-51/2013/G3P[9], was isolated from the stool of a 9-year-old female hospitalized with acute watery diarrhea in August 2012 in South Korea using a cell culture system, and its genome was analyzed. The complete genomic constellation of the CAU12-2-51 strain revealed a novel genotype constellation for human rotavirus, G3-P[9]-I2-R2-C2-M2-A3-N2-T3-E3-H3. Phylogenetic analysis revealed that the CAU12-2-51 strain originated from feline- and bovine-like reassortment strains. The genes encoding VP4, VP7, NSP1, NSP3, NSP4, and NSP5 were related to human/feline-like and feline rotavirus strains, whereas the remaining five genes encoding VP1, VP2, VP3, VP6, and NSP2 were related to the human/bovine-like and bovine rotavirus strains. This novel strain was identified for the first time, providing evidence of feline/bovine-to-human transmission of rotavirus. The data presented herein provide information regarding rotavirus diversity and evolution.

Jeong, Sunyoung; Than, Van Thai; Lim, Inseok; Kim, Wonyong

2014-01-01

374

Investigation of the Causes of Breast Cancer at the Cellular Level: Isolation of In Vivo Binding Sites of the Human Origin Recognition Complex.  

National Technical Information Service (NTIS)

We study the process of DNA replication in proliferating human cells. Our efforts are directed to the identification and characterization of proteins that promote DNA replication ('initiators') as well as the DNA sequences recognized by them ('replicators...

J. Mendez B. Stillman

2002-01-01

375

Evolution of influenza A virus PB2 genes: implications for evolution of the ribonucleoprotein complex and origin of human influenza A virus.  

PubMed Central

Phylogenetic analysis of 20 influenza A virus PB2 genes showed that PB2 genes have evolved into the following four major lineages: (i) equine/Prague/56 (EQPR56); (ii and iii) two distinct avian PB2 lineages, one containing FPV/34 and H13 gull virus strains and the other containing North American avian and recent equine strains; and (iv) human virus strains joined with classic swine virus strains (i.e., H1N1 swine virus strains related to swine/Iowa/15/30). The human virus lineage showed the greatest divergence from its root relative to other lineages. The estimated nucleotide evolutionary rate for the human PB2 lineage was 1.82 x 10(-3) changes per nucleotide per year, which is within the range of published estimates for NP and NS genes of human influenza A viruses. At the amino acid level, PB2s of human viruses have accumulated 34 amino acid changes over the past 55 years. In contrast, the avian PB2 lineages showed much less evolution, e.g., recent avian PB2s showed as few as three amino acid changes relative to the avian root. The completion of evolutionary analyses of the PB1, PB2, PA and NP genes of the ribonucleoprotein (RNP) complex permits comparison of evolutionary pathways. Different patterns of evolution among the RNP genes indicate that the genes of the complex are not coevolving as a unit. Evolution of the PB1 and PB2 genes is less correlated with host-specific factors, and their proteins appear to be evolving more slowly than NP and PA. This suggests that protein functional constraints are limiting the evolutionary divergence of PB1 and PB2 genes. The parallel host-specific evolutionary pathways of the NP and PA genes suggest that these proteins are coevolving in response to host-specific factors. PB2s of human influenza A viruses share a common ancestor with classic swine virus PB2s, and the pattern of evolution suggests that the ancestor was an avian virus PB2. This same pattern of evolution appears in the other genes of the RNP complex. Antigenic studies of HA and NA proteins and sequence comparisons of NS and M genes also suggest a close ancestry for these genes in human and classic swine viruses. From our review of the evolutionary patterns of influenza A virus genes, we propose the following hypothesis: the common ancestor to current strains of human and classic swine influenza viruses predated the 1918 human pandemic virus and was recently derived from the avian host reservoir.

Gorman, O T; Donis, R O; Kawaoka, Y; Webster, R G

1990-01-01

376

The first modern human dispersals across Africa.  

PubMed

The emergence of more refined chronologies for climate change and archaeology in prehistoric Africa, and for the evolution of human mitochondrial DNA (mtDNA), now make it feasible to test more sophisticated models of early modern human dispersals suggested by mtDNA distributions. Here we have generated 42 novel whole-mtDNA genomes belonging to haplogroup L0, the most divergent clade in the maternal line of descent, and analysed them alongside the growing database of African lineages belonging to L0's sister clade, L1'6. We propose that the last common ancestor of modern human mtDNAs (carried by "mitochondrial Eve") possibly arose in central Africa ~180 ka, at a time of low population size. By ~130 ka two distinct groups of anatomically modern humans co-existed in Africa: broadly, the ancestors of many modern-day Khoe and San populations in the south and a second central/eastern African group that includes the ancestors of most extant worldwide populations. Early modern human dispersals correlate with climate changes, particularly the tropical African "megadroughts" of MIS 5 (marine isotope stage 5, 135-75 ka) which paradoxically may have facilitated expansions in central and eastern Africa, ultimately triggering the dispersal out of Africa of people carrying haplogroup L3 ~60 ka. Two south to east migrations are discernible within haplogroup LO. One, between 120 and 75 ka, represents the first unambiguous long-range modern human dispersal detected by mtDNA and might have allowed the dispersal of several markers of modernity. A second one, within the last 20 ka signalled by L0d, may have been responsible for the spread of southern click-consonant languages to eastern Africa, contrary to the view that these eastern examples constitute relicts of an ancient, much wider distribution. PMID:24236171

Rito, Teresa; Richards, Martin B; Fernandes, Verónica; Alshamali, Farida; Cerny, Viktor; Pereira, Luísa; Soares, Pedro

2013-01-01

377

The First Modern Human Dispersals across Africa  

PubMed Central

The emergence of more refined chronologies for climate change and archaeology in prehistoric Africa, and for the evolution of human mitochondrial DNA (mtDNA), now make it feasible to test more sophisticated models of early modern human dispersals suggested by mtDNA distributions. Here we have generated 42 novel whole-mtDNA genomes belonging to haplogroup L0, the most divergent clade in the maternal line of descent, and analysed them alongside the growing database of African lineages belonging to L0’s sister clade, L1’6. We propose that the last common ancestor of modern human mtDNAs (carried by “mitochondrial Eve”) possibly arose in central Africa ~180 ka, at a time of low population size. By ~130 ka two distinct groups of anatomically modern humans co-existed in Africa: broadly, the ancestors of many modern-day Khoe and San populations in the south and a second central/eastern African group that includes the ancestors of most extant worldwide populations. Early modern human dispersals correlate with climate changes, particularly the tropical African “megadroughts” of MIS 5 (marine isotope stage 5, 135–75 ka) which paradoxically may have facilitated expansions in central and eastern Africa, ultimately triggering the dispersal out of Africa of people carrying haplogroup L3 ~60 ka. Two south to east migrations are discernible within haplogroup LO. One, between 120 and 75 ka, represents the first unambiguous long-range modern human dispersal detected by mtDNA and might have allowed the dispersal of several markers of modernity. A second one, within the last 20 ka signalled by L0d, may have been responsible for the spread of southern click-consonant languages to eastern Africa, contrary to the view that these eastern examples constitute relicts of an ancient, much wider distribution.

Rito, Teresa; Richards, Martin B.; Fernandes, Veronica; Alshamali, Farida; Cerny, Viktor

2013-01-01

378

Peat Bog Archives: from human history, vegetation change and Holocene climate, to atmospheric dusts and trace elements of natural and anthropogenic origin  

Microsoft Academic Search

For at least two centuries, peat has been recognized as an excellent archive of environmental change. William Rennie (1807), for example, interpreted stratigraphic changes in Scottish bogs not only in terms of natural changes in paleoclimate, but was also able to identify environmental changes induced by humans, namely deforestation and the hydrological impacts which result from such activities. The use

William Shotyk

2010-01-01

379

Distribution of Class 1 Integrons with IS26-Mediated Deletions in Their 3'-Conserved Segments in Escherichia coli of Human and Animal Origin  

Microsoft Academic Search

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

Fay E. Dawes; Alexander Kuzevski; Karl A. Bettelheim; Michael A. Hornitzky; Steven P. Djordjevic; Mark J. Walker; Christophe Herman

2010-01-01

380

Intracellular locations of replication proteins and the origin of replication during chromosome duplication in the slowly growing human pathogen Helicobacter pylori.  

PubMed

We followed the position of the replication complex in the pathogenic bacterium Helicobacter pylori using antibodies raised against the single-stranded DNA binding protein (HpSSB) and the replicative helicase (HpDnaB). The position of the replication origin, oriC, was also localized in growing cells by fluorescence in situ hybridization (FISH) with fluorescence-labeled DNA sequences adjacent to the origin. The replisome assembled at oriC near one of the cell poles, and the two forks moved together toward the cell center as replication progressed in the growing cell. Termination and resolution of the forks occurred near midcell, on one side of the septal membrane. The duplicated copies of oriC did not separate until late in elongation, when the daughter chromosomes segregated into bilobed nucleoids, suggesting sister chromatid cohesion at or near the oriC region. Components of the replication machinery, viz., HpDnaB and HpDnaG (DNA primase), were found associated with the cell membrane. A model for the assembly and location of the H. pylori replication machinery during chromosomal duplication is presented. PMID:24363345

Sharma, Atul; Kamran, Mohammad; Verma, Vijay; Dasgupta, Santanu; Dhar, Suman Kumar

2014-03-01

381

Human Infections Attributable to the d-Tartrate-Fermenting Variant of Salmonella enterica Serovar Paratyphi B in Germany Originate in Reptiles and, on Rare Occasions, Poultry  

PubMed Central

In this study, the population structure, incidence, and potential sources of human infection caused by the d-tartrate-fermenting variant of Salmonella enterica serovar Paratyphi B [S. Paratyphi B (dT+)] was investigated. In Germany, the serovar is frequently isolated from broilers. Therefore, a selection of 108 epidemiologically unrelated S. enterica serovar Paratyphi B (dT+) strains isolated in Germany between 2002 and 2010 especially from humans, poultry/poultry meat, and reptiles was investigated by phenotypic and genotypic methods. Strains isolated from poultry and products thereof were strongly associated with multilocus sequence type ST28 and showed antimicrobial multiresistance profiles. Pulsed-field gel electrophoresis XbaI profiles were highly homogeneous, with only a few minor XbaI profile variants. All strains isolated from reptiles, except one, were strongly associated with ST88, another distantly related type. Most of the strains were susceptible to antimicrobial agents, and XbaI profiles were heterogeneous. Strains isolated from humans yielded seven sequence types (STs) clustering in three distantly related lineages. The first lineage, comprising five STs, represented mainly strains belonging to ST43 and ST149. The other two lineages were represented only by one ST each, ST28 and ST88. The relatedness of strains based on the pathogenicity gene repertoire (102 markers tested) was mostly in agreement with the multilocus sequence type. Because ST28 was frequently isolated from poultry but rarely in humans over the 9-year period investigated, overall, this study indicates that in Germany S. enterica serovar Paratyphi B (dT+) poses a health risk preferentially by contact with reptiles and, to a less extent, by exposure to poultry or poultry meat.

Toboldt, Anne; Tietze, Erhard; Helmuth, Reiner; Fruth, Angelika; Junker, Ernst

2012-01-01

382

Human Granulocyte-Macrophage Colony-Stimulating Factor is a Growth Factor Active on a Variety of Cell Types of Nonhemopoietic Origin  

Microsoft Academic Search

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a member of a family of glycoprotein hormones that stimulate the proliferation and differentiation of hemopoietic cells in vitro and in vivo. We now report that human GM-CSF can also stimulate the proliferation of two osteogenic sarcoma cell lines, a breast carcinoma cell line, a simian virus 40-transformed marrow stromal cell line, and normal marrow

Shoukat Dedhar; Louis Gaboury; Paula Galloway; Connie Eaves

1988-01-01

383

qnrD, a Novel Gene Conferring Transferable Quinolone Resistance in Salmonella enterica Serovar Kentucky and Bovismorbificans Strains of Human Origin  

Microsoft Academic Search

In a previous study, four Salmonella isolates from humans in the Henan province of China showed reduced susceptibility to ciprofloxacin (MIC, 0.125 to 0.25 g\\/ml) but were susceptible to nalidixic acid (MIC, 4 to 8 g\\/ml). All isolates were negative for known qnr genes (A, B, and S), aac(6)Ib-cr, and mutations in gyrA and parC. Plasmid DNA was extracted from

L. M. Cavaco; H. Hasman; S. Xia; F. M. Aarestrup

2009-01-01

384

Diversity of Listeria monocytogenes isolates of human and food origin studied by serotyping, automated ribotyping and pulsed-field gel electrophoresis.  

PubMed

Automated ribotyping, pulsed-field gel electrophoresis (PFGE) and serotyping were evaluated for the epidemiological study of isolates of Listeria monocytogenes collected in Finland in 1997-1999 from human blood (n = 116) and the food industry (n = 72). The isolates divided into six serotypes, 23 EcoRI ribotypes, 54 AscI PFGE types, and 57 final subtypes if all results were combined. The discrimination index of ribotyping was lower (0.873) than that of PFGE (0.946). Two final subtypes dominated among human isolates, and identical subtypes were also found among food industry isolates. All PFGE types were serotype-specific, whereas two ribotypes included isolates of two serotypes. Isolates of serotype 3a, involved in an outbreak in Finland in 1999, matched one of these ribotypes, which also included some food industry isolates of serotype 1/2a. Ribotyping with EcoRI would not have been sufficient to define the outbreak in Finland caused by serotype 3a isolates. Although ribotyping is applicable as the first method in outbreak situations, human and food isolates with identical ribotypes should be investigated further by PFGE. PMID:15191386

Lukinmaa, S; Aarnisalo, K; Suihko, M-L; Siitonen, A

2004-06-01

385

A human Na+/H+ antiporter sharing evolutionary origins with bacterial NhaA may be a candidate gene for essential hypertension  

PubMed Central

Phylogenetic analysis of the cation/proton antiporter superfamily has uncovered a previously unknown clade of genes in metazoan genomes, including two previously uncharacterized human isoforms, NHA1 and NHA2, found in tandem on human chromosome 4. The NHA (sodium hydrogen antiporter) family members share significant sequence similarity with Escherichia coli NhaA, including a conserved double aspartate motif in predicted transmembrane 5. We show that HsNHA2 (Homo sapiens NHA2) resides on the plasma membrane and, in polarized MDCK cells, localizes to the apical domain. Analysis of mouse tissues indicates that NHA2 is ubiquitous. When expressed in the yeast Saccharomyces cerevisiae lacking endogenous cation/proton antiporters and pumps, HsNHA2 can confer tolerance to Li+ and Na+ ions but not to K+. HsNHA2 transformants accumulated less Li+ than the salt-sensitive host; however, mutagenic replacement of the conserved aspartates abolished all observed phenotypes. Functional complementation by HsNHA2 was insensitive to amiloride, a characteristic inhibitor of plasma membrane sodium hydrogen exchanger isoforms, but was inhibited by phloretin. These are hallmarks of sodium–lithium countertransport activity, a highly heritable trait correlating with hypertension. Our findings raise the possibility that NHA genes may contribute to sodium–lithium countertransport activity and salt homeostasis in humans.

Xiang, Minghui; Feng, Mingye; Muend, Sabina; Rao, Rajini

2007-01-01

386

The Evolutionary Origin of Man Can Be Traced in the Layers of Defunct Ancestral Alpha Satellites Flanking the Active Centromeres of Human Chromosomes  

PubMed Central

Alpha satellite domains that currently function as centromeres of human chromosomes are flanked by layers of older alpha satellite, thought to contain dead centromeres of primate progenitors, which lost their function and the ability to homogenize satellite repeats, upon appearance of a new centromere. Using cladistic analysis of alpha satellite monomers, we elucidated complete layer patterns on chromosomes 8, 17, and X and related them to each other and to primate alpha satellites. We show that discrete and chronologically ordered alpha satellite layers are partially symmetrical around an active centromere and their succession is partially shared in non-homologous chromosomes. The layer structure forms a visual representation of the human evolutionary lineage with layers corresponding to ancestors of living primates and to entirely fossil taxa. Surprisingly, phylogenetic comparisons suggest that alpha satellite arrays went through periods of unusual hypermutability after they became “dead” centromeres. The layer structure supports a model of centromere evolution where new variants of a satellite repeat expanded periodically in the genome by rounds of inter-chromosomal transfer/amplification. Each wave of expansion covered all or many chromosomes and corresponded to a new primate taxon. Complete elucidation of the alpha satellite phylogenetic record would give a unique opportunity to number and locate the positions of major extinct taxa in relation to human ancestors shared with extant primates. If applicable to other satellites in non-primate taxa, analysis of centromeric layers could become an invaluable tool for phylogenetic studies.

Shepelev, Valery A.; Alexandrov, Alexander A.; Yurov, Yuri B.; Alexandrov, Ivan A.

2009-01-01

387

Cytological Studies of Human Meiosis: Sex-Specific Differences in Recombination Originate at, or Prior to, Establishment of Double-Strand Breaks  

PubMed Central

Meiotic recombination is sexually dimorphic in most mammalian species, including humans, but the basis for the male:female differences remains unclear. In the present study, we used cytological methodology to directly compare recombination levels between human males and females, and to examine possible sex-specific differences in upstream events of double-strand break (DSB) formation and synaptic initiation. Specifically, we utilized the DNA mismatch repair protein MLH1 as a marker of recombination events, the RecA homologue RAD51 as a surrogate for DSBs, and the synaptonemal complex proteins SYCP3 and/or SYCP1 to examine synapsis between homologs. Consistent with linkage studies, genome-wide recombination levels were higher in females than in males, and the placement of exchanges varied between the sexes. Subsequent analyses of DSBs and synaptic initiation sites indicated similar male:female differences, providing strong evidence that sex-specific differences in recombination rates are established at or before the formation of meiotic DSBs. We then asked whether these differences might be linked to variation in the organization of the meiotic axis and/or axis-associated DNA and, indeed, we observed striking male:female differences in synaptonemal complex (SC) length and DNA loop size. Taken together, our observations suggest that sex specific differences in recombination in humans may derive from chromatin differences established prior to the onset of the recombination pathway.

Gruhn, Jennifer R.; Rubio, Carmen; Broman, Karl W.; Hunt, Patricia A.; Hassold, Terry

2013-01-01

388

Multiple ethnic origins of mitochondrial DNA lineages for the population of Mauritius.  

PubMed

This article reports on the first genetic assessment of the contemporary Mauritian population. Small island nodes such as Mauritius played a critical role in historic globalization processes and revealing high-resolution details of labour sourcing is crucial in order to better understand early-modern diaspora events. Mauritius is a particularly interesting case given detailed historic accounts attesting to European (Dutch, French and British), African and Asian points of origin. Ninety-seven samples were analysed for mitochondrial DNA to begin unravelling the complex dynamics of the island's modern population. In corroboration with general demographic information, the majority of maternal lineages were derived from South Asia (58.76%), with Malagasy (16.60%), East/Southeast Asian (11.34%) and Sub-Saharan African (10.21%) also making significant contributions. This study pinpoints specific regional origins for the South Asian genetic contribution, showing a greater influence on the contemporary population from northern and southeast India. Moreover, the analysis of lineages related to the slave trade demonstrated that Madagascar and East Asia were the main centres of origin, with less influence from West Africa. PMID:24676463

Fregel, Rosa; Seetah, Krish; Betancor, Eva; Suárez, Nicolás M; ?aval, Diego; Caval, Saša; Janoo, Anwar; Pestano, Jose

2014-01-01

389

Multiple Ethnic Origins of Mitochondrial DNA Lineages for the Population of Mauritius  

PubMed Central

This article reports on the first genetic assessment of the contemporary Mauritian population. Small island nodes such as Mauritius played a critical role in historic globalization processes and revealing high-resolution details of labour sourcing is crucial in order to better understand early-modern diaspora events. Mauritius is a particularly interesting case given detailed historic accounts attesting to European (Dutch, French and British), African and Asian points of origin. Ninety-seven samples were analysed for mitochondrial DNA to begin unravelling the complex dynamics of the island's modern population. In corroboration with general demographic information, the majority of maternal lineages were derived from South Asia (58.76%), with Malagasy (16.60%), East/Southeast Asian (11.34%) and Sub-Saharan African (10.21%) also making significant contributions. This study pinpoints specific regional origins for the South Asian genetic contribution, showing a greater influence on the contemporary population from northern and southeast India. Moreover, the analysis of lineages related to the slave trade demonstrated that Madagascar and East Asia were the main centres of origin, with less influence from West Africa.

Betancor, Eva; Suarez, Nicolas M.; Calaon, Diego; Caval, Sasa; Janoo, Anwar; Pestano, Jose

2014-01-01

390

Estimating the distribution of probable age-at-death from dental remains of immature human fossils.  

PubMed

In two historic longitudinal growth studies, Moorrees et al. (Am J Phys Anthropol 21 (1963) 99-108; J Dent Res 42 (1963) 1490-1502) presented the "mean attainment age" for stages of tooth development for 10 permanent tooth types and three deciduous tooth types. These findings were presented graphically to assess the rate of tooth formation in living children and to age immature skeletal remains. Despite being widely cited, these graphical data are difficult to implement because there are no accompanying numerical values for the parameters underlying the growth data. This analysis generates numerical parameters from the data reported by Moorrees et al. by digitizing 358 points from these tooth formation graphs using DataThief III, version 1.5. Following the original methods, the digitized points for each age transition were conception-corrected and converted to the logarithmic scale to determine a median attainment age for each dental formation stage. These values are subsequently used to estimate age-at-death distributions for immature individuals using a single tooth or multiple teeth, including estimates for 41 immature early modern humans and 25 immature Neandertals. Within-tooth variance is calculated for each age estimate based on a single tooth, and a between-tooth component of variance is calculated for age estimates based on two or more teeth to account for the increase in precision that comes from using additional teeth. Finally, we calculate the relative probability of observing a particular dental formation sequence given known-age reference information and demonstrate its value in estimating age for immature fossil specimens. PMID:22190291

Shackelford, Laura L; Stinespring Harris, Ashley E; Konigsberg, Lyle W

2012-02-01

391

NASA's Origins Program  

NSDL National Science Digital Library

Since time immemorial, humans have asked such fundamental questions as "Are we alone" and "Where did we come from?". Taking on some of those fundamental questions through the use of scientific inquiry is the Origins program, operated under the auspices of NASA. As an introductory essay on the program authored by Alan Dresser on the site suggests: "The eruptive growth of 20th century astronomy has brought us an appreciation of how vast, old, and unearthly the universe is, and has left humanity struggling with a sense of our own significance consistent with the reality of who and what we are." With that rather awe-inspiring thought in mind, visitors will want to comb through the many insightful sections of the site, including those that provide answers (or at least what we know so far) to such questions as "Is there life on planets outside the solar system?" Additionally, visitors can read about NASA's different missions and learn about the new technologies under development that will allow voyages of discovery into space to continue these explorations over the coming decades.

2008-01-11

392

Simultaneous Detection of Human Mitochondrial DNA and Nuclear-Inserted Mitochondrial-origin Sequences (NumtS) using Forensic mtDNA Amplification Strategies and Pyrosequencing Technology.  

PubMed

Next-generation sequencing technologies enable the identification of minor mitochondrial DNA variants with higher sensitivity than Sanger methods, allowing for enhanced identification of minor variants. In this study, mixtures of human mtDNA control region amplicons were subjected to pyrosequencing to determine the detection threshold of the Roche GS Junior(®) instrument (Roche Applied Science, Indianapolis, IN). In addition to expected variants, a set of reproducible variants was consistently found in reads from one particular amplicon. A BLASTn search of the variant sequence revealed identity to a segment of a 611-bp nuclear insertion of the mitochondrial control region (NumtS) spanning the primer-binding sites of this amplicon (Nature 1995;378:489). Primers (Hum Genet 2012;131:757; Hum Biol 1996;68:847) flanking the insertion were used to confirm the presence or absence of the NumtS in buccal DNA extracts from twenty donors. These results further our understanding of human mtDNA variation and are expected to have a positive impact on the interpretation of mtDNA profiles using deep-sequencing methods in casework. PMID:24738853

Bintz, Brittania J; Dixon, Groves B; Wilson, Mark R

2014-07-01

393

Humans and Ferrets with Prior H1N1 Influenza Virus Infections Do Not Exhibit Evidence of Original Antigenic Sin after Infection or Vaccination with the 2009 Pandemic H1N1 Influenza Virus.  

PubMed

The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus. PMID:24648486

O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J; Subbarao, Kanta

2014-05-01

394

The presence and origin of autoantibodies against ?4 and ?7 nicotinic acetylcholine receptors in the human blood: possible relevance to Alzheimer's pathology.  

PubMed

Alzheimer's disease (AD) is characterized by a loss of ?4?2 and ?7 nicotinic acetylcholine receptors (nAChRs) in the brain and severe memory impairments. Previously, we found that antibodies elicited against extracellular domain of ?7 nAChR subunit decreased the number of ?7 nAChRs in the brains of mice and impaired episodic memory. Here we show that antibodies capable to bind ?7(1-208) are present in the blood of both healthy humans and AD patients. In healthy individuals, their capacity to compete with [(125)-I]-?-bungarotoxin for the binding to ?7(1-208) increased with age. The level of such antibodies was significantly elevated in children with severe form of obstructive bronchitis and in mice injected with Lewis lung carcinoma cells expressing both ?4?2 and ?7 nAChRs. Elevated antibody levels were accompanied with decreased surface nAChRs on the blood lymphocytes of children and of mice immunized with ?7(1-208). Among AD patients, the level of ?7 nAChR-specific antibodies was significantly larger in people 62.5 ± 1.5 years old with moderate or severe AD stages (15.2 ± 1.3 MMSE scores) compared to those of 76 ± 1.5 years old with the mild (22.7 ± 0.1 MMSE scores) AD stage. We concluded that ?7(1-208) nAChR-specific antibodies found in the human blood are formed as a result of common infections accompanied with the destruction of respiratory epithelium. Elevated blood plasma levels of ?7(1-208) nAChR-specific antibodies are characteristic for the early-onset AD and, therefore, are suggested as one of the risk factors for the development of this form of the disease. PMID:21593571

Koval, Lyudmyla; Lykhmus, Olena; Kalashnyk, Olena; Bachinskaya, Nataliya; Kravtsova, Ganna; Soldatkina, Mariya; Zouridakis, Marios; Stergiou, Christos; Tzartos, Socrates; Tsetlin, Victor; Komisarenko, Sergiy; Skok, Maryna

2011-01-01

395

Bioenergetics in human evolution and disease: implications for the origins of biological complexity and the missing genetic variation of common diseases  

PubMed Central

Two major inconsistencies exist in the current neo-Darwinian evolutionary theory that random chromosomal mutations acted on by natural selection generate new species. First, natural selection does not require the evolution of ever increasing complexity, yet this is the hallmark of biology. Second, human chromosomal DNA sequence variation is predominantly either neutral or deleterious and is insufficient to provide the variation required for speciation or for predilection to common diseases. Complexity is explained by the continuous flow of energy through the biosphere that drives the accumulation of nucleic acids and information. Information then encodes complex forms. In animals, energy flow is primarily mediated by mitochondria whose maternally inherited mitochondrial DNA (mtDNA) codes for key genes for energy metabolism. In mammals, the mtDNA has a very high mutation rate, but the deleterious mutations are removed by an ovarian selection system. Hence, new mutations that subtly alter energy metabolism are continuously introduced into the species, permitting adaptation to regional differences in energy environments. Therefore, the most phenotypically significant gene variants arise in the mtDNA, are regional, and permit animals to occupy peripheral energy environments where rarer nuclear DNA (nDNA) variants can accumulate, leading to speciation. The neutralist–selectionist debate is then a consequence of mammals having two different evolutionary strategies: a fast mtDNA strategy for intra-specific radiation and a slow nDNA strategy for speciation. Furthermore, the missing genetic variation for common human diseases is primarily mtDNA variation plus regional nDNA variants, both of which have been missed by large, inter-population association studies.

Wallace, Douglas C.

2013-01-01

396

Evidence for the origin of the unoccupied oestrogen receptor in nuclei of a human breast-cancer cell line (MCF-7)  

PubMed Central

The origin of the unoccupied nuclear oestrogen receptor (Rn) was studied. Three working hypotheses were investigated. (a) Rn is a dissociation product of the oestrogen occupied nuclear receptor (ERn). (b) ERn is only partially occupied, so that additional binding may occur at 0°C (the temperature at which oestradiol saturates unoccupied sites). (c) Rn is derived from the penetration of unoccupied cytoplasmic receptor (Rc) into the nucleus. The MCF-7 cell line was used as a model in the present investigation. The amount of unoccupied receptors was measured by saturation with 7.5nm-[3H]oestradiol at 0°C, whereas the occupied receptors were measured by exchange at 30°C. The cells at preconfluency were exposed to a medium fortified with 10nm-[3H]oestradiol for 1h, washed and cultured up to 5 days in fresh growth medium. The distribution of oestradiol receptors was determined before exposure and during the following 5 days. After 1h exposure only ERn was found in the nuclear fraction. Thereafter ERn declined continuously so that on day 5 it approached 15% of its value measured 1h after exposure. Although after 3 days about 80% of ERn disappeared no Rn appeared, which contradicts hypotheses (a) and (b). On day 4 Rn and Rc appeared simultaneously. The appearance of Rn and Rc was not prevented by culturing the cells in an oestrogen-free medium, supporting hypothesis (c). Exposure of cells to increasing concentration of [3H]oestradiol (0.1–10nm) for 1h resulted in a parallel increase in ERn without increasing the amount of unoccupied binding sites, which contradicts hypothesis (b). The present study supports the hypothesis (c), i.e., Rc may also penetrate the nucleus without binding to oestradiol.

Geier