Science.gov

Sample records for early human ancestors

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

    PubMed Central

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

    2015-01-01

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

  2. Diet and the evolution of the earliest human ancestors.

    PubMed

    Teaford, M F; Ungar, P S

    2000-12-01

    Over the past decade, discussions of the evolution of the earliest human ancestors have focused on the locomotion of the australopithecines. Recent discoveries in a broad range of disciplines have raised important questions about the influence of ecological factors in early human evolution. Here we trace the cranial and dental traits of the early australopithecines through time, to show that between 4.4 million and 2.3 million years ago, the dietary capabilities of the earliest hominids changed dramatically, leaving them well suited for life in a variety of habitats and able to cope with significant changes in resource availability associated with long-term and short-term climatic fluctuations.

  3. Virtual ancestor reconstruction: Revealing the ancestor of modern humans and Neandertals.

    PubMed

    Mounier, Aurélien; Mirazón Lahr, Marta

    2016-02-01

    The timing and geographic origin of the common ancestor of modern humans and Neandertals remain controversial. A poor Pleistocene hominin fossil record and the evolutionary complexities introduced by dispersals and regionalisation of lineages have fuelled taxonomic uncertainty, while new ancient genomic data have raised completely new questions. Here, we use maximum likelihood and 3D geometric morphometric methods to predict possible morphologies of the last common ancestor of modern humans and Neandertals from a simplified, fully resolved phylogeny. We describe the fully rendered 3D shapes of the predicted ancestors of humans and Neandertals, and assess their similarity to individual fossils or populations of fossils of Pleistocene age. Our results support models of an Afro-European ancestral population in the Middle Pleistocene (Homo heidelbergensis sensu lato) and further predict an African origin for this ancestral population. PMID:26852813

  4. Diet and the evolution of the earliest human ancestors.

    PubMed

    Teaford, M F; Ungar, P S

    2000-12-01

    Over the past decade, discussions of the evolution of the earliest human ancestors have focused on the locomotion of the australopithecines. Recent discoveries in a broad range of disciplines have raised important questions about the influence of ecological factors in early human evolution. Here we trace the cranial and dental traits of the early australopithecines through time, to show that between 4.4 million and 2.3 million years ago, the dietary capabilities of the earliest hominids changed dramatically, leaving them well suited for life in a variety of habitats and able to cope with significant changes in resource availability associated with long-term and short-term climatic fluctuations. PMID:11095758

  5. Stride lengths, speed and energy costs in walking of Australopithecus afarensis: using evolutionary robotics to predict locomotion of early human ancestors.

    PubMed

    Sellers, William I; Cain, Gemma M; Wang, Weijie; Crompton, Robin H

    2005-12-22

    This paper uses techniques from evolutionary robotics to predict the most energy-efficient upright walking gait for the early human relative Australopithecus afarensis, based on the proportions of the 3.2 million year old AL 288-1 'Lucy' skeleton, and matches predictions against the nearly contemporaneous (3.5-3.6 million year old) Laetoli fossil footprint trails. The technique creates gaits de novo and uses genetic algorithm optimization to search for the most efficient patterns of simulated muscular contraction at a variety of speeds. The model was first verified by predicting gaits for living human subjects, and comparing costs, stride lengths and speeds to experimentally determined values for the same subjects. Subsequent simulations for A. afarensis yield estimates of the range of walking speeds from 0.6 to 1.3 m s-1 at a cost of 7.0 J kg-1 m-1 for the lowest speeds, falling to 5.8 J kg-1 m-1 at 1.0 m s-1, and rising to 6.2 J kg-1 m-1 at the maximum speed achieved. Speeds previously estimated for the makers of the Laetoli footprint trails (0.56 or 0.64 m s-1 for Trail 1, 0.72 or 0.75 m s-1 for Trail 2/3) may have been underestimated, substantially so for Trail 2/3, with true values in excess of 0.7 and 1.0 m s-1, respectively. The predictions conflict with suggestions that A. afarensis used a 'shuffling' gait, indicating rather that the species was a fully competent biped.

  6. Evolution of life history and behavior in Hominidae: towards phylogenetic reconstruction of the chimpanzee-human last common ancestor.

    PubMed

    Duda, Pavel; Zrzavý, Jan

    2013-10-01

    The origin of the fundamental behavioral differences between humans and our closest living relatives is one of the central issues of evolutionary anthropology. The prominent, chimpanzee-based referential model of early hominin behavior has recently been challenged on the basis of broad multispecies comparisons and newly discovered fossil evidence. Here, we argue that while behavioral data on extant great apes are extremely relevant for reconstruction of ancestral behaviors, these behaviors should be reconstructed trait by trait using formal phylogenetic methods. Using the widely accepted hominoid phylogenetic tree, we perform a series of character optimization analyses using 65 selected life-history and behavioral characters for all extant hominid species. This analysis allows us to reconstruct the character states of the last common ancestors of Hominoidea, Hominidae, and the chimpanzee-human last common ancestor. Our analyses demonstrate that many fundamental behavioral and life-history attributes of hominids (including humans) are evidently ancient and likely inherited from the common ancestor of all hominids. However, numerous behaviors present in extant great apes represent their own terminal autapomorphies (both uniquely derived and homoplastic). Any evolutionary model that uses a single extant species to explain behavioral evolution of early hominins is therefore of limited use. In contrast, phylogenetic reconstruction of ancestral states is able to provide a detailed suite of behavioral, ecological and life-history characters for each hypothetical ancestor. The living great apes therefore play an important role for the confident identification of the traits found in the chimpanzee-human last common ancestor, some of which are likely to represent behaviors of the fossil hominins.

  7. Inbreeding, Pedigree Size, and the Most Recent Common Ancestor of Humanity

    PubMed Central

    Lachance, Joseph

    2009-01-01

    How many generations ago did the common ancestor of all present-day individuals live, and how does inbreeding affect this estimate? The number of ancestors within family trees determines the timing of the most recent common ancestor of humanity. However, mating is often non-random and inbreeding is ubiquitous in natural populations. Rates of pedigree growth are found for multiple types of inbreeding. This data is then combined with models of global population structure to estimate biparental coalescence times. When pedigrees for regular systems of mating are constructed, the growth rates of inbred populations contain Fibonacci n-step constants. The timing of the most recent common ancestor depends on global population structure, the mean rate of pedigree growth, mean fitness, and current population size. Inbreeding reduces the number of ancestors in a pedigree, pushing back global common ancestry times. These results are consistent with the remarkable findings of previous studies: all humanity shares common ancestry in the recent past. PMID:19679139

  8. Scapular shape of extant hominoids and the African ape/modern human last common ancestor.

    PubMed

    Green, David J; Spiewak, Ted A; Seitelman, Brielle; Gunz, Philipp

    2016-05-01

    Newly discovered early hominin fossil scapulae have bolstered investigations of scapular shape, which have long been used to interpret behavioral variation among primates. However, unexpected similarities between Pongo and Homo - particularly in scapular spine orientation - have raised questions about the functional utility of scapular morphology and its phylogenetic context in the hominin lineage. Not surprisingly, significant disagreement surrounds disparate morphological reconstructions of the modern human/African ape last common ancestor (LCA). Our study utilizes geometric morphometric (GM) approaches - two employing homologous, anatomical landmarks and a "spine-free" alternative using 98 sliding semilandmarks along the boundary of the subscapular fossa. The landmark-based "wireframe" GM analysis principally sorted groups by spine orientation: Homo and Pongo were similar to one another with more transversely-oriented spines as compared to Hylobates and the African apes. In contrast, Homo and Gorilla clustered together in our semilandmark analysis with superoinferiorly broad blades. Pan scapulae were similar, but had more mediolaterally compressed blades and laterally-positioned superior angles. Hylobates was superoinferiorly narrow, yet obliquely expanded relative to the vertebral border. Pongo scapulae were unique among hominoids in being nearly as broad as they were long. Previously documented 'convergence' of Homo and Pongo scapulae appears to be principally driven by similarities in spine orientation, rather than overall blade shape. Therefore, we contend that it is more parsimonious to reconstruct the African ape/Homo LCA scapula as being Gorilla-like, especially in light of similar characterizations of certain fossil hominin scapulae. Accordingly, the evolution of Pan (highly oblique spine and laterally-situated superior angle) and Homo (transversely-oriented spine) scapular morphology would have involved relatively minor shifts from this ancestral

  9. Scapular shape of extant hominoids and the African ape/modern human last common ancestor.

    PubMed

    Green, David J; Spiewak, Ted A; Seitelman, Brielle; Gunz, Philipp

    2016-05-01

    Newly discovered early hominin fossil scapulae have bolstered investigations of scapular shape, which have long been used to interpret behavioral variation among primates. However, unexpected similarities between Pongo and Homo - particularly in scapular spine orientation - have raised questions about the functional utility of scapular morphology and its phylogenetic context in the hominin lineage. Not surprisingly, significant disagreement surrounds disparate morphological reconstructions of the modern human/African ape last common ancestor (LCA). Our study utilizes geometric morphometric (GM) approaches - two employing homologous, anatomical landmarks and a "spine-free" alternative using 98 sliding semilandmarks along the boundary of the subscapular fossa. The landmark-based "wireframe" GM analysis principally sorted groups by spine orientation: Homo and Pongo were similar to one another with more transversely-oriented spines as compared to Hylobates and the African apes. In contrast, Homo and Gorilla clustered together in our semilandmark analysis with superoinferiorly broad blades. Pan scapulae were similar, but had more mediolaterally compressed blades and laterally-positioned superior angles. Hylobates was superoinferiorly narrow, yet obliquely expanded relative to the vertebral border. Pongo scapulae were unique among hominoids in being nearly as broad as they were long. Previously documented 'convergence' of Homo and Pongo scapulae appears to be principally driven by similarities in spine orientation, rather than overall blade shape. Therefore, we contend that it is more parsimonious to reconstruct the African ape/Homo LCA scapula as being Gorilla-like, especially in light of similar characterizations of certain fossil hominin scapulae. Accordingly, the evolution of Pan (highly oblique spine and laterally-situated superior angle) and Homo (transversely-oriented spine) scapular morphology would have involved relatively minor shifts from this ancestral

  10. Fossil hominin shoulders support an African ape-like last common ancestor of humans and chimpanzees

    PubMed Central

    Young, Nathan M.; Capellini, Terence D.; Roach, Neil T.; Alemseged, Zeresenay

    2015-01-01

    Reconstructing the behavioral shifts that drove hominin evolution requires knowledge of the timing, magnitude, and direction of anatomical changes over the past ∼6–7 million years. These reconstructions depend on assumptions regarding the morphotype of the Homo–Pan last common ancestor (LCA). However, there is little consensus for the LCA, with proposed models ranging from African ape to orangutan or generalized Miocene ape-like. The ancestral state of the shoulder is of particular interest because it is functionally associated with important behavioral shifts in hominins, such as reduced arboreality, high-speed throwing, and tool use. However, previous morphometric analyses of both living and fossil taxa have yielded contradictory results. Here, we generated a 3D morphospace of ape and human scapular shape to plot evolutionary trajectories, predict ancestral morphologies, and directly test alternative evolutionary hypotheses using the hominin fossil evidence. We show that the most parsimonious model for the evolution of hominin shoulder shape starts with an African ape-like ancestral state. We propose that the shoulder evolved gradually along a single morphocline, achieving modern human-like configuration and function within the genus Homo. These data are consistent with a slow, progressive loss of arboreality and increased tool use throughout human evolution. PMID:26351685

  11. No known hominin species matches the expected dental morphology of the last common ancestor of Neanderthals and modern humans

    PubMed Central

    Gómez-Robles, Aida; Bermúdez de Castro, José María; Arsuaga, Juan-Luis; Carbonell, Eudald; Polly, P. David

    2013-01-01

    A central problem in paleoanthropology is the identity of the last common ancestor of Neanderthals and modern humans ([N-MH]LCA). Recently developed analytical techniques now allow this problem to be addressed using a probabilistic morphological framework. This study provides a quantitative reconstruction of the expected dental morphology of the [N-MH]LCA and an assessment of whether known fossil species are compatible with this ancestral position. We show that no known fossil species is a suitable candidate for being the [N-MH]LCA and that all late Early and Middle Pleistocene taxa from Europe have Neanderthal dental affinities, pointing to the existence of a European clade originated around 1 Ma. These results are incongruent with younger molecular divergence estimates and suggest at least one of the following must be true: (i) European fossils and the [N-MH]LCA selectively retained primitive dental traits; (ii) molecular estimates of the divergence between Neanderthals and modern humans are underestimated; or (iii) phenotypic divergence and speciation between both species were decoupled such that phenotypic differentiation, at least in dental morphology, predated speciation. PMID:24145426

  12. The facial skeleton of the chimpanzee-human last common ancestor

    PubMed Central

    Cobb, Samuel N

    2008-01-01

    This review uses the current morphological evidence to evaluate the facial morphology of the hypothetical last common ancestor (LCA) of the chimpanzee/bonobo (panin) and human (hominin) lineages. Some of the problems involved in reconstructing ancestral morphologies so close to the formation of a lineage are discussed. These include the prevalence of homoplasy and poor phylogenetic resolution due to a lack of defining derived features. Consequently the list of hypothetical features expected in the face of the LCA is very limited beyond its hypothesized similarity to extant Pan. It is not possible to determine with any confidence whether the facial morphology of any of the current candidate LCA taxa (Ardipithecus kadabba, Ardipithecus ramidus, Orrorin tugenensis and Sahelanthropus tchadensis) is representative of the LCA, or a stem hominin, or a stem panin or, in some cases, a hominid predating the emergence of the hominin lineage. The major evolutionary trends in the hominin lineage subsequent to the LCA are discussed in relation to the dental arcade and dentition, subnasal morphology and the size, position and prognathism of the facial skeleton. PMID:18380866

  13. The facial skeleton of the chimpanzee-human last common ancestor.

    PubMed

    Cobb, Samuel N

    2008-04-01

    This review uses the current morphological evidence to evaluate the facial morphology of the hypothetical last common ancestor (LCA) of the chimpanzee/bonobo (panin) and human (hominin) lineages. Some of the problems involved in reconstructing ancestral morphologies so close to the formation of a lineage are discussed. These include the prevalence of homoplasy and poor phylogenetic resolution due to a lack of defining derived features. Consequently the list of hypothetical features expected in the face of the LCA is very limited beyond its hypothesized similarity to extant Pan. It is not possible to determine with any confidence whether the facial morphology of any of the current candidate LCA taxa (Ardipithecus kadabba, Ardipithecus ramidus, Orrorin tugenensis and Sahelanthropus tchadensis) is representative of the LCA, or a stem hominin, or a stem panin or, in some cases, a hominid predating the emergence of the hominin lineage. The major evolutionary trends in the hominin lineage subsequent to the LCA are discussed in relation to the dental arcade and dentition, subnasal morphology and the size, position and prognathism of the facial skeleton.

  14. The universal ancestor

    NASA Technical Reports Server (NTRS)

    Woese, C.

    1998-01-01

    A genetic annealing model for the universal ancestor of all extant life is presented; the name of the model derives from its resemblance to physical annealing. The scenario pictured starts when "genetic temperatures" were very high, cellular entities (progenotes) were very simple, and information processing systems were inaccurate. Initially, both mutation rate and lateral gene transfer levels were elevated. The latter was pandemic and pervasive to the extent that it, not vertical inheritance, defined the evolutionary dynamic. As increasingly complex and precise biological structures and processes evolved, both the mutation rate and the scope and level of lateral gene transfer, i.e., evolutionary temperature, dropped, and the evolutionary dynamic gradually became that characteristic of modern cells. The various subsystems of the cell "crystallized," i.e., became refractory to lateral gene transfer, at different stages of "cooling," with the translation apparatus probably crystallizing first. Organismal lineages, and so organisms as we know them, did not exist at these early stages. The universal phylogenetic tree, therefore, is not an organismal tree at its base but gradually becomes one as its peripheral branchings emerge. The universal ancestor is not a discrete entity. It is, rather, a diverse community of cells that survives and evolves as a biological unit. This communal ancestor has a physical history but not a genealogical one. Over time, this ancestor refined into a smaller number of increasingly complex cell types with the ancestors of the three primary groupings of organisms arising as a result.

  15. Phylogenomic Analyses Indicate that Early Fungi Evolved Digesting Cell Walls of Algal Ancestors of Land Plants.

    PubMed

    Chang, Ying; Wang, Sishuo; Sekimoto, Satoshi; Aerts, Andrea L; Choi, Cindy; Clum, Alicia; LaButti, Kurt M; Lindquist, Erika A; Yee Ngan, Chew; Ohm, Robin A; Salamov, Asaf A; Grigoriev, Igor V; Spatafora, Joseph W; Berbee, Mary L

    2015-05-14

    As decomposers, fungi are key players in recycling plant material in global carbon cycles. We hypothesized that genomes of early diverging fungi may have inherited pectinases from an ancestral species that had been able to extract nutrients from pectin-containing land plants and their algal allies (Streptophytes). We aimed to infer, based on pectinase gene expansions and on the organismal phylogeny, the geological timing of the plant-fungus association. We analyzed 40 fungal genomes, three of which, including Gonapodya prolifera, were sequenced for this study. In the organismal phylogeny from 136 housekeeping loci, Rozella diverged first from all other fungi. Gonapodya prolifera was included among the flagellated, predominantly aquatic fungal species in Chytridiomycota. Sister to Chytridiomycota were the predominantly terrestrial fungi including zygomycota I and zygomycota II, along with the ascomycetes and basidiomycetes that comprise Dikarya. The Gonapodya genome has 27 genes representing five of the seven classes of pectin-specific enzymes known from fungi. Most of these share a common ancestry with pectinases from Dikarya. Indicating functional and sequence similarity, Gonapodya, like many Dikarya, can use pectin as a carbon source for growth in pure culture. Shared pectinases of Dikarya and Gonapodya provide evidence that even ancient aquatic fungi had adapted to extract nutrients from the plants in the green lineage. This implies that 750 million years, the estimated maximum age of origin of the pectin-containing streptophytes represents a maximum age for the divergence of Chytridiomycota from the lineage including Dikarya.

  16. Hairless mutation: a driving force of humanization from a human–ape common ancestor by enforcing upright walking while holding a baby with both hands

    PubMed Central

    Sutou, Shizuyo

    2012-01-01

    Three major characteristics distinguish humans from other primates: bipedality, practical nakedness, and the family as a social unit. A hairless mutation introduced into the chimpanzee/human last common ancestor (CLCA) 6 million years ago (Mya) diverged hairless human and hairy chimpanzee lineages. All primates except humans can carry their babies without using their hands. A hairless mother would be forced to stand and walk upright. Her activities would be markedly limited. The male partner would have to collect food and carry it to her by hand to keep her and their baby from starving; irresponsible and selfish males could not have left their offspring. The mother would have sexually accepted her partner at any time as a reward for food. Sexual relations irrespective of estrus cycles might have strengthened the pair bond. Molecular and paleontological dating indicates that CLCA existed 6 Mya, and early hominin fossils show that they were bipeds, indicating that humanization from CLCA occurred rapidly. A single mutation in animals with scalp hair is known to induce hairless phenotype (ectodermal dysplasia). Bipedalism and hairlessness are disadvantageous traits; only those who could survive trials and tribulations in cooperation with family members must have been able to evolve as humans. PMID:22404045

  17. Strong Selective Sweeps on the X Chromosome in the Human-Chimpanzee Ancestor Explain Its Low Divergence.

    PubMed

    Dutheil, Julien Y; Munch, Kasper; Nam, Kiwoong; Mailund, Thomas; Schierup, Mikkel H

    2015-08-01

    The human and chimpanzee X chromosomes are less divergent than expected based on autosomal divergence. We study incomplete lineage sorting patterns between humans, chimpanzees and gorillas to show that this low divergence can be entirely explained by megabase-sized regions comprising one-third of the X chromosome, where polymorphism in the human-chimpanzee ancestral species was severely reduced. We show that background selection can explain at most 10% of this reduction of diversity in the ancestor. Instead, we show that several strong selective sweeps in the ancestral species can explain it. We also report evidence of population specific sweeps in extant humans that overlap the regions of low diversity in the ancestral species. These regions further correspond to chromosomal sections shown to be devoid of Neanderthal introgression into modern humans. This suggests that the same X-linked regions that undergo selective sweeps are among the first to form reproductive barriers between diverging species. We hypothesize that meiotic drive is the underlying mechanism causing these two observations. PMID:26274919

  18. Strong Selective Sweeps on the X Chromosome in the Human-Chimpanzee Ancestor Explain Its Low Divergence

    PubMed Central

    Dutheil, Julien Y.; Munch, Kasper; Nam, Kiwoong; Mailund, Thomas; Schierup, Mikkel H.

    2015-01-01

    The human and chimpanzee X chromosomes are less divergent than expected based on autosomal divergence. We study incomplete lineage sorting patterns between humans, chimpanzees and gorillas to show that this low divergence can be entirely explained by megabase-sized regions comprising one-third of the X chromosome, where polymorphism in the human-chimpanzee ancestral species was severely reduced. We show that background selection can explain at most 10% of this reduction of diversity in the ancestor. Instead, we show that several strong selective sweeps in the ancestral species can explain it. We also report evidence of population specific sweeps in extant humans that overlap the regions of low diversity in the ancestral species. These regions further correspond to chromosomal sections shown to be devoid of Neanderthal introgression into modern humans. This suggests that the same X-linked regions that undergo selective sweeps are among the first to form reproductive barriers between diverging species. We hypothesize that meiotic drive is the underlying mechanism causing these two observations. PMID:26274919

  19. Human Diversity and the Genealogy of Languages: Noah as the Founding Ancestor of the Chinese

    ERIC Educational Resources Information Center

    Hutton, Christopher

    2008-01-01

    The characteristics which were held to define the Chinese language within the Western intellectual tradition placed it for a time at the centre in discussions of the genealogy of mankind. The dominant premodern paradigm for the explanation of human linguistic diversity was Biblical exegesis, as discussed and elaborated within the framework of…

  20. Ancient horizontal transfers of retrotransposons between birds and ancestors of human pathogenic nematodes.

    PubMed

    Suh, Alexander; Witt, Christopher C; Menger, Juliana; Sadanandan, Keren R; Podsiadlowski, Lars; Gerth, Michael; Weigert, Anne; McGuire, Jimmy A; Mudge, Joann; Edwards, Scott V; Rheindt, Frank E

    2016-01-01

    Parasite host switches may trigger disease emergence, but prehistoric host ranges are often unknowable. Lymphatic filariasis and loiasis are major human diseases caused by the insect-borne filarial nematodes Brugia, Wuchereria and Loa. Here we show that the genomes of these nematodes and seven tropical bird lineages exclusively share a novel retrotransposon, AviRTE, resulting from horizontal transfer (HT). AviRTE subfamilies exhibit 83-99% nucleotide identity between genomes, and their phylogenetic distribution, paleobiogeography and invasion times suggest that HTs involved filarial nematodes. The HTs between bird and nematode genomes took place in two pantropical waves, >25-22 million years ago (Myr ago) involving the Brugia/Wuchereria lineage and >20-17 Myr ago involving the Loa lineage. Contrary to the expectation from the mammal-dominated host range of filarial nematodes, we hypothesize that these major human pathogens may have independently evolved from bird endoparasites that formerly infected the global breadth of avian biodiversity. PMID:27097561

  1. Ancient horizontal transfers of retrotransposons between birds and ancestors of human pathogenic nematodes

    PubMed Central

    Suh, Alexander; Witt, Christopher C.; Menger, Juliana; Sadanandan, Keren R.; Podsiadlowski, Lars; Gerth, Michael; Weigert, Anne; McGuire, Jimmy A.; Mudge, Joann; Edwards, Scott V.; Rheindt, Frank E.

    2016-01-01

    Parasite host switches may trigger disease emergence, but prehistoric host ranges are often unknowable. Lymphatic filariasis and loiasis are major human diseases caused by the insect-borne filarial nematodes Brugia, Wuchereria and Loa. Here we show that the genomes of these nematodes and seven tropical bird lineages exclusively share a novel retrotransposon, AviRTE, resulting from horizontal transfer (HT). AviRTE subfamilies exhibit 83–99% nucleotide identity between genomes, and their phylogenetic distribution, paleobiogeography and invasion times suggest that HTs involved filarial nematodes. The HTs between bird and nematode genomes took place in two pantropical waves, >25–22 million years ago (Myr ago) involving the Brugia/Wuchereria lineage and >20–17 Myr ago involving the Loa lineage. Contrary to the expectation from the mammal-dominated host range of filarial nematodes, we hypothesize that these major human pathogens may have independently evolved from bird endoparasites that formerly infected the global breadth of avian biodiversity. PMID:27097561

  2. Ancient horizontal transfers of retrotransposons between birds and ancestors of human pathogenic nematodes.

    PubMed

    Suh, Alexander; Witt, Christopher C; Menger, Juliana; Sadanandan, Keren R; Podsiadlowski, Lars; Gerth, Michael; Weigert, Anne; McGuire, Jimmy A; Mudge, Joann; Edwards, Scott V; Rheindt, Frank E

    2016-04-21

    Parasite host switches may trigger disease emergence, but prehistoric host ranges are often unknowable. Lymphatic filariasis and loiasis are major human diseases caused by the insect-borne filarial nematodes Brugia, Wuchereria and Loa. Here we show that the genomes of these nematodes and seven tropical bird lineages exclusively share a novel retrotransposon, AviRTE, resulting from horizontal transfer (HT). AviRTE subfamilies exhibit 83-99% nucleotide identity between genomes, and their phylogenetic distribution, paleobiogeography and invasion times suggest that HTs involved filarial nematodes. The HTs between bird and nematode genomes took place in two pantropical waves, >25-22 million years ago (Myr ago) involving the Brugia/Wuchereria lineage and >20-17 Myr ago involving the Loa lineage. Contrary to the expectation from the mammal-dominated host range of filarial nematodes, we hypothesize that these major human pathogens may have independently evolved from bird endoparasites that formerly infected the global breadth of avian biodiversity.

  3. Ancient wolf genome reveals an early divergence of domestic dog ancestors and admixture into high-latitude breeds.

    PubMed

    Skoglund, Pontus; Ersmark, Erik; Palkopoulou, Eleftheria; Dalén, Love

    2015-06-01

    The origin of domestic dogs is poorly understood [1-15], with suggested evidence of dog-like features in fossils that predate the Last Glacial Maximum [6, 9, 10, 14, 16] conflicting with genetic estimates of a more recent divergence between dogs and worldwide wolf populations [13, 15, 17-19]. Here, we present a draft genome sequence from a 35,000-year-old wolf from the Taimyr Peninsula in northern Siberia. We find that this individual belonged to a population that diverged from the common ancestor of present-day wolves and dogs very close in time to the appearance of the domestic dog lineage. We use the directly dated ancient wolf genome to recalibrate the molecular timescale of wolves and dogs and find that the mutation rate is substantially slower than assumed by most previous studies, suggesting that the ancestors of dogs were separated from present-day wolves before the Last Glacial Maximum. We also find evidence of introgression from the archaic Taimyr wolf lineage into present-day dog breeds from northeast Siberia and Greenland, contributing between 1.4% and 27.3% of their ancestry. This demonstrates that the ancestry of present-day dogs is derived from multiple regional wolf populations. PMID:26004765

  4. Ancient wolf genome reveals an early divergence of domestic dog ancestors and admixture into high-latitude breeds.

    PubMed

    Skoglund, Pontus; Ersmark, Erik; Palkopoulou, Eleftheria; Dalén, Love

    2015-06-01

    The origin of domestic dogs is poorly understood [1-15], with suggested evidence of dog-like features in fossils that predate the Last Glacial Maximum [6, 9, 10, 14, 16] conflicting with genetic estimates of a more recent divergence between dogs and worldwide wolf populations [13, 15, 17-19]. Here, we present a draft genome sequence from a 35,000-year-old wolf from the Taimyr Peninsula in northern Siberia. We find that this individual belonged to a population that diverged from the common ancestor of present-day wolves and dogs very close in time to the appearance of the domestic dog lineage. We use the directly dated ancient wolf genome to recalibrate the molecular timescale of wolves and dogs and find that the mutation rate is substantially slower than assumed by most previous studies, suggesting that the ancestors of dogs were separated from present-day wolves before the Last Glacial Maximum. We also find evidence of introgression from the archaic Taimyr wolf lineage into present-day dog breeds from northeast Siberia and Greenland, contributing between 1.4% and 27.3% of their ancestry. This demonstrates that the ancestry of present-day dogs is derived from multiple regional wolf populations.

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

    PubMed

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

    2016-02-25

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

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

    PubMed

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

    2016-02-25

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

  7. Independent evolution of knuckle-walking in African apes shows that humans did not evolve from a knuckle-walking ancestor.

    PubMed

    Kivell, Tracy L; Schmitt, Daniel

    2009-08-25

    Despite decades of debate, it remains unclear whether human bipedalism evolved from a terrestrial knuckle-walking ancestor or from a more generalized, arboreal ape ancestor. Proponents of the knuckle-walking hypothesis focused on the wrist and hand to find morphological evidence of this behavior in the human fossil record. These studies, however, have not examined variation or development of purported knuckle-walking features in apes or other primates, data that are critical to resolution of this long-standing debate. Here we present novel data on the frequency and development of putative knuckle-walking features of the wrist in apes and monkeys. We use these data to test the hypothesis that all knuckle-walking apes share similar anatomical features and that these features can be used to reliably infer locomotor behavior in our extinct ancestors. Contrary to previous expectations, features long-assumed to indicate knuckle-walking behavior are not found in all African apes, show different developmental patterns across species, and are found in nonknuckle-walking primates as well. However, variation among African ape wrist morphology can be clearly explained if we accept the likely independent evolution of 2 fundamentally different biomechanical modes of knuckle-walking: an extended wrist posture in an arboreal environment (Pan) versus a neutral, columnar hand posture in a terrestrial environment (Gorilla). The presence of purported knuckle-walking features in the hominin wrist can thus be viewed as evidence of arboreality, not terrestriality, and provide evidence that human bipedalism evolved from a more arboreal ancestor occupying the ecological niche common to all living apes.

  8. The effective population sizes of the anthropoid ancestors of the human-chimpanzee lineage provide insights on the historical biogeography of the great apes.

    PubMed

    Schrago, Carlos G

    2014-01-01

    The recent development of methods that apply coalescent theory to phylogenetic problems has enabled the study of the population-level phenomena that drove the diversification of anthropoid primates. Effective population size, Ne, is one of the main parameters that constitute the theoretical underpinning of these new analytical approaches. For this reason, the ancestral N(e) of selected primate lineages has been thoroughly investigated. However, for some of these lineages, the estimates of ancestral N(e) reported in several studies present significant variation. This is the case for the common ancestor of humans and chimpanzees. Moreover, several ancestral anthropoid lineages have been ignored in the studies conducted so far. Because N(e) is fundamental to understand historic species demography, it is a crucial component of a complete description of the historical scenario of primate evolution. It also provides information that is helpful for differentiating between competing biogeographical hypotheses. In this study, the effective population sizes of the anthropoid ancestors of the human-chimp lineage are inferred using data sets of coding and noncoding sequences. A general pattern of a serial decline of population sizes is found between the ancestral lineage of Anthropoidea and that of Homo and Pan. When the theoretical distribution of gene trees was derived from the parametric estimates obtained, it closely corresponded to the empirical frequency of inferred gene trees along the genome. The most abrupt decrease of N(e) was found between the ancestors of all great apes and those of the African great apes alone. This suggests the occurrence of a genetic bottleneck during the evolution of Homininae, which corroborates the origin of African apes from a Eurasian ancestor.

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

    PubMed Central

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

    2016-01-01

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

  10. Non-Darwinian estimation: My ancestors, my genes' ancestors

    PubMed Central

    Weiss, Kenneth M.; Long, Jeffrey C.

    2009-01-01

    There is widespread interest in characterizing the organization of human genetic variation around the world from a population perspective. Related to this are attempts to describe the pattern of genetic variation in the human species generally, including “recreational” genomics, the genome-based estimation of the ancestry of individuals. These approaches rest on subtle concepts of variation, time, and ancestry that are perhaps not widely appreciated. They share the idea that there are, or were, discrete panmictic human populations such that every person is either a member of such a population or is an admixed descendant of them. Ancestry fraction estimation is biased by assumptions about past and present human population structure, as when we trace ancestry to hypothetical unmixed ancestral populations, or assign an individual's ancestry to continental populations that are indistinguishable from classical “races.” Attempts to identify even individuals' local subpopulations are less precise than most (geneticists included) expect, because that is usually based on a small portion of a person's ancestry, relative to the much larger pool of comparably related ancestors. It is easier to show that two people have some relationship than to show who or where the actual ancestor was. There is an important distinction between individuals' demographic ancestry and the ancestry of their genes. Despite superficial appearances, these interpretations of genetic data are often based on typological rather than Darwinian thinking, raising important issues about the questions that are actually being asked. PMID:19411595

  11. The deuterostome ancestor.

    PubMed

    Gerhart, John

    2006-12-01

    Hemichordates, the phylum of bilateral animals closest to chordates, can illuminate the evolutionary origins of various chordate traits to determine whether these were already present in a shared ancestor (the deuterostome ancestor) or were evolved within the chordate line. We find that an anteroposterior map of gene expression domains, representing 42 genes of neural patterning, is closely similar in hemichordates and chordates, though it is restricted to the neural ectoderm in chordates whereas in hemichordates, which have a diffuse nervous system, it encircles the whole body. This map allows an accurate alignment of the anterioposterior axes of members of the two groups. We propose that this map dates back at least to the deuterostome ancestor. The map of dorsoventral expression domains, organized along a Bmp-Chordin developmental axis, is also similar in the two groups in terms of many gene expression domains and for the placement of the gill slits, heart, and post-anal tail. The two groups, however, differ in two major respects along this axis. The nervous system and epidermis are not segregated into distinct territories in hemichordates, as they are in chordates, and furthermore, the mouth is on the Chordin side in hemichordates but the Bmp side in chordates. The dorsoventral dimension has undergone extensive modification in the chordate line, including centralization of the nervous system, segregation of epidermis, derivation of the notochord, perhaps from the gut midline, and relocation of the mouth. Based on the shared domain maps, speculations can be made for the remodeling of the body axis in the chordate line.

  12. The galaxy ancestor problem

    NASA Astrophysics Data System (ADS)

    Disney, M. J.; Lang, R. H.

    2012-11-01

    The Hubble Space Telescope (HST) findsgalaxies whose Tolman dimming exceeds 10 mag. Could evolution alone explain these as our ancestor galaxies or could they be representatives of quite a different dynasty whose descendants are no longer prominent today? We explore the latter hypothesis and argue that surface brightness selection effects naturally bring into focus quite different dynasties from different redshifts. Thus, the HST z = 7 galaxies could be examples of galaxies whose descendants are both too small and too choked with dust to be recognizable in our neighbourhood easily today. Conversely, the ancestors of the Milky Way and its obvious neighbours would have completely sunk below the sky at z > 1.2, unless they were more luminous in the past, although their diffused light could account for the missing re-ionization flux. This Succeeding Prominent Dynasties Hypothesis (SPDH) fits the existing observations both naturally and well even without evolution, including the bizarre distributions of galaxy surface brightness found in deep fields, the angular size ˜(1 + z)-1 law, 'downsizing' which turns out to be an 'illusion' in the sense that it does not imply evolution, 'infant mortality', that is, the discrepancy between stars born and stars seen, the existence of 'red nuggets', and finally the recently discovered and unexpected excess of quasar absorption line damped Lyα systems at high redshift. If galaxies were not significantly brighter in the past and the SPDH were true, then a large proportion of galaxies could remain sunk from sight, possibly at all redshifts, and these sunken galaxies could supply the missing re-ionization flux. We show that fishing these sunken galaxies out of the sky by their optical emissions alone is practically impossible, even when they are nearby. More ingenious methods are needed to detect them. It follows that disentangling galaxy evolution through studying ever higher redshift galaxies may be a forlorn hope because one could

  13. Ontogeny of the maxilla in Neanderthals and their ancestors.

    PubMed

    Lacruz, Rodrigo S; Bromage, Timothy G; O'Higgins, Paul; Arsuaga, Juan-Luis; Stringer, Chris; Godinho, Ricardo Miguel; Warshaw, Johanna; Martínez, Ignacio; Gracia-Tellez, Ana; de Castro, José María Bermúdez; Carbonell, Eudald

    2015-01-01

    Neanderthals had large and projecting (prognathic) faces similar to those of their putative ancestors from Sima de los Huesos (SH) and different from the retracted modern human face. When such differences arose during development and the morphogenetic modifications involved are unknown. We show that maxillary growth remodelling (bone formation and resorption) of the Devil's Tower (Gibraltar 2) and La Quina 18 Neanderthals and four SH hominins, all sub-adults, show extensive bone deposition, whereas in modern humans extensive osteoclastic bone resorption is found in the same regions. This morphogenetic difference is evident by ∼5 years of age. Modern human faces are distinct from those of the Neanderthal and SH fossils in part because their postnatal growth processes differ markedly. The growth remodelling identified in these fossil hominins is shared with Australopithecus and early Homo but not with modern humans suggesting that the modern human face is developmentally derived. PMID:26639346

  14. Ontogeny of the maxilla in Neanderthals and their ancestors

    PubMed Central

    Lacruz, Rodrigo S.; Bromage, Timothy G.; O'Higgins, Paul; Arsuaga, Juan-Luis; Stringer, Chris; Godinho, Ricardo Miguel; Warshaw, Johanna; Martínez, Ignacio; Gracia-Tellez, Ana; de Castro, José María Bermúdez; Carbonell, Eudald

    2015-01-01

    Neanderthals had large and projecting (prognathic) faces similar to those of their putative ancestors from Sima de los Huesos (SH) and different from the retracted modern human face. When such differences arose during development and the morphogenetic modifications involved are unknown. We show that maxillary growth remodelling (bone formation and resorption) of the Devil's Tower (Gibraltar 2) and La Quina 18 Neanderthals and four SH hominins, all sub-adults, show extensive bone deposition, whereas in modern humans extensive osteoclastic bone resorption is found in the same regions. This morphogenetic difference is evident by ∼5 years of age. Modern human faces are distinct from those of the Neanderthal and SH fossils in part because their postnatal growth processes differ markedly. The growth remodelling identified in these fossil hominins is shared with Australopithecus and early Homo but not with modern humans suggesting that the modern human face is developmentally derived. PMID:26639346

  15. Origin of Clothing Lice Indicates Early Clothing Use by Anatomically Modern Humans in Africa

    PubMed Central

    Toups, Melissa A.; Kitchen, Andrew; Light, Jessica E.; Reed, David L.

    2011-01-01

    Clothing use is an important modern behavior that contributed to the successful expansion of humans into higher latitudes and cold climates. Previous research suggests that clothing use originated anywhere between 40,000 and 3 Ma, though there is little direct archaeological, fossil, or genetic evidence to support more specific estimates. Since clothing lice evolved from head louse ancestors once humans adopted clothing, dating the emergence of clothing lice may provide more specific estimates of the origin of clothing use. Here, we use a Bayesian coalescent modeling approach to estimate that clothing lice diverged from head louse ancestors at least by 83,000 and possibly as early as 170,000 years ago. Our analysis suggests that the use of clothing likely originated with anatomically modern humans in Africa and reinforces a broad trend of modern human developments in Africa during the Middle to Late Pleistocene. PMID:20823373

  16. Early depictions of the human anterior nasal septum.

    PubMed

    Pirsig, Wolfgang; Sokiranski, Roman

    2006-06-01

    In the literature, remarks on the depiction of the anterior nasal septum in prehistoric times cannot be found. Studying works of art from some archaeological sites of Asia, Asia Minor, Near East, Egypt, and Southeastern Europe the anatomical depiction of the columella and the nostrils in human figures are shown. These figures or heads, partly appearing as masks, were made of ivory, stone, marble, terracotta, steatite, reeds and clay, or of burned limestone. Faces and figures sculpted in the time between the Upper Palaeolithic (30,000 - 25,000 BC) and the Early Bronze Age (3,300 - 2,400 BC) are presented as examples of our ancestors' outstanding skill to create works of art with an astonishing ability to observe anatomical details. The tendency to create a human nose in a natural manner can already be recognized in the figurines of the Upper Palaeolithic.

  17. What did our ancestors eat?

    PubMed

    Garn, S M; Leonard, W R

    1989-11-01

    Over the millennia various hominoids and hominids have subsisted on very different dietaries, depending on climate, hunting proficiency, food-processing technology, and available foods. The Australopithecines were not browsers and fruit-eaters with very high intakes of vitamin C; rather they were scavengers of kills made by other animals. The hominids who followed did include some cold-climate hunters of large game, but the amount of animal protein decreased with the advent of grain-gathering and decreased further with the introduction of cereal agriculture, with a concomitant decrease in body size. From what we know about food adequacy, preparation, and storage, the notion that the postulated "primitive" diet was generally adequate, safe, and prudent can be rejected. Over evolutionary time, many of our ancestors ate poorly, especially during climate extremes, and they were often at risk for vitamin deficiencies, food-borne diseases, and neurotoxins. Until the advent of modern processing technologies, dirt, grit, and fiber constituted a large part of most early diets. PMID:2689923

  18. Aping our ancestors

    NASA Astrophysics Data System (ADS)

    Ennos, Roland

    2014-08-01

    Roland Ennos argues that the abilities of the great apes to cope in the dangerous mechanical environment of the forest canopy are part of the human species' intellectual inheritance and are intimately connected with our abilities as physicists.

  19. Supermassive black hole ancestors

    NASA Astrophysics Data System (ADS)

    Petri, A.; Ferrara, A.; Salvaterra, R.

    2012-05-01

    In the attempt to alleviate the difficulties created by their early formation, we study a model in which supermassive black holes (SMBHs) can grow by the combined action of gas accretion on heavy seeds and mergers of both heavy ? and light ? seeds. The former results from the direct collapse of gas in ? K, H2-free haloes; the latter are the end product of a standard H2-based star formation process. The H2-free condition is attained by exposing haloes to a strong (J21≳ 103) Lyman-Werner ultraviolet (UV) background produced by both accreting BHs and stars, thus establishing a self-regulated growth regime. We find that this condition is met already at z˜ 18 in the highly biased regions in which quasars are born. The key parameter allowing the formation of SMBHs by z= 6-7 is the fraction of haloes that can form heavy seeds: the minimum requirement is that fheavy≳ 0.001; SMBH as large as 2 × 1010 M⊙ can be obtained when fheavy approaches unity. Independently of fheavy, the model produces a high-z stellar bulge-BH mass relation which is steeper than the local one, implying that SMBHs formed before their bulge was in place. The formation of heavy seeds, allowed by the Lyman-Werner radiative feedback in the quasar-forming environment, is crucial to achieve a fast growth of the SMBH by merger events in the early phases of its evolution, i.e. z≳ 7. The UV photon production is largely dominated by stars in galaxies, i.e. BH accretion radiation is subdominant. Interestingly, we find that the final mass of light BHs and of the SMBH in the quasar is roughly equal by z= 6; by the same time, only 19 per cent of the initial baryon content has been converted into stars. The SMBH growth is dominated at all epochs z > 7.2 by mergers (exceeding accretion by a factor of 2-50); at later times, accretion becomes by far the most important growth channel. We finally discuss possible shortcomings of the model.

  20. The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson's disease and originates from a common ancestor

    PubMed Central

    Goldwurm, S; Fonzo, A; Simons, E; Rohe, C; Zini, M; Canesi, M; Tesei, S; Zecchinelli, A; Antonini, A; Mariani, C; Meucci, N; Sacilotto, G; Sironi, F; Salani, G; Ferreira, J; Chien, H; Fabrizio, E; Vanacore, N; Libera, A; Stocchi, F; Diroma, C; Lamberti, P; Sampaio, C; Meco, G; Barbosa, E; Bertoli-Avella, A; Breedveld, G; Oostra, B; Pezzoli, G; Bonifati, V

    2005-01-01

    Background: Mutations in the gene Leucine-Rich Repeat Kinase 2 (LRRK2) were recently identified as the cause of PARK8 linked autosomal dominant Parkinson's disease. Objective: To study recurrent LRRK2 mutations in a large sample of patients from Italy, including early (<50 years) and late onset familial and sporadic Parkinson's disease. Results: Among 629 probands, 13 (2.1%) were heterozygous carriers of the G2019S mutation. The mutation frequency was higher among familial (5.1%, 9/177) than among sporadic probands (0.9%, 4/452) (p<0.002), and highest among probands with one affected parent (8.7%, 6/69) (p<0.001). There was no difference in the frequency of the G2019S mutation in probands with early v late onset disease. Among 600 probands, one heterozygous R1441C but no R1441G or Y1699C mutations were detected. None of the four mutations was found in Italian controls. Haplotype analysis in families from five countries suggested that the G2019S mutation originated from a single ancient founder. The G2019S mutation was associated with the classical Parkinson's disease phenotype and a broad range of onset age (34 to 73 years). Conclusions: G2019S is the most common genetic determinant of Parkinson's disease identified so far. It is especially frequent among cases with familial Parkinson's disease of both early and late onset, but less common among sporadic cases. These findings have important implications for diagnosis and genetic counselling in Parkinson's disease. PMID:16272257

  1. Ancestors of modern plant crops.

    PubMed

    Salse, Jérôme

    2016-04-01

    Recent accumulation of plant genomic resources offers the opportunity to compare modern genomes and model their evolutionary history from their reconstructed Most Recent Common Ancestors (MRCAs) that can be used as a guide to unveil the forces driving the evolutionary success of angiosperms and ultimately to perform applied translational research from models to crops. This article reviews the current state of art of recent structural comparative genomics studies through ancestral genome reconstruction, that is, the field of in silico paleogenomics.

  2. The evolutionary history of the hominin hand since the last common ancestor of Pan and Homo.

    PubMed

    Tocheri, Matthew W; Orr, Caley M; Jacofsky, Marc C; Marzke, Mary W

    2008-04-01

    Molecular evidence indicates that the last common ancestor of the genus Pan and the hominin clade existed between 8 and 4 million years ago (Ma). The current fossil record indicates the Pan-Homo last common ancestor existed at least 5 Ma and most likely between 6 and 7 Ma. Together, the molecular and fossil evidence has important consequences for interpreting the evolutionary history of the hand within the tribe Hominini (hominins). Firstly, parsimony supports the hypothesis that the hand of the last common ancestor most likely resembled that of an extant great ape overall (Pan, Gorilla, and Pongo), and that of an African ape in particular. Second, it provides a context for interpreting the derived changes to the hand that have evolved in various hominins. For example, the Australopithecus afarensis hand is likely derived in comparison with that of the Pan-Homo last common ancestor in having shorter fingers relative to thumb length and more proximo-distally oriented joints between its capitate, second metacarpal, and trapezium. This evidence suggests that these derived features evolved prior to the intensification of stone tool-related hominin behaviors beginning around 2.5 Ma. However, a majority of primitive features most likely present in the Pan-Homo last common ancestor are retained in the hands of Australopithecus, Paranthropus/early Homo, and Homo floresiensis. This evidence suggests that further derived changes to the hands of other hominins such as modern humans and Neandertals did not evolve until after 2.5 Ma and possibly even later than 1.5 Ma, which is currently the earliest evidence of Acheulian technology. The derived hands of modern humans and Neandertals may indicate a morphological commitment to tool-related manipulative behaviors beyond that observed in other hominins, including those (e.g. H. floresiensis) which may be descended from earlier tool-making species. PMID:18380869

  3. Transcriptome Encyclopedia of Early Human Development.

    PubMed

    Sahakyan, Anna; Plath, Kathrin

    2016-05-01

    Our understanding of human pre-implantation development is limited by the availability of human embryos and cannot completely rely on mouse studies. Petropoulos et al. now provide an extensive transcriptome analysis of a large number of human pre-implantation embryos at single-cell resolution, revealing previously unrecognized features unique to early human development.

  4. The last common bilaterian ancestor

    NASA Technical Reports Server (NTRS)

    Erwin, Douglas H.; Davidson, Eric H.

    2002-01-01

    Many regulatory genes appear to be utilized in at least superficially similar ways in the development of particular body parts in Drosophila and in chordates. These similarities have been widely interpreted as functional homologies, producing the conventional view of the last common protostome-deuterostome ancestor (PDA) as a complex organism that possessed some of the same body parts as modern bilaterians. Here we discuss an alternative view, in which the last common PDA had a less complex body plan than is frequently conceived. This reconstruction alters expectations for Neoproterozoic fossil remains that could illustrate the pathways of bilaterian evolution.

  5. The Evolution of Brains from Early Mammals to Humans.

    PubMed

    Kaas, Jon H

    2013-01-01

    The large size and complex organization of the human brain makes it unique among primate brains. In particular, the neocortex constitutes about 80% of the brain, and this cortex is subdivided into a large number of functionally specialized regions, the cortical areas. Such a brain mediates accomplishments and abilities unmatched by any other species. How did such a brain evolve? Answers come from comparative studies of the brains of present-day mammals and other vertebrates in conjunction with information about brain sizes and shapes from the fossil record, studies of brain development, and principles derived from studies of scaling and optimal design. Early mammals were small, with small brains, an emphasis on olfaction, and little neocortex. Neocortex was transformed from the single layer of output pyramidal neurons of the dorsal cortex of earlier ancestors to the six layers of all present-day mammals. This small cap of neocortex was divided into 20-25 cortical areas, including primary and some of the secondary sensory areas that characterize neocortex in nearly all mammals today. Early placental mammals had a corpus callosum connecting the neocortex of the two hemispheres, a primary motor area, M1, and perhaps one or more premotor areas. One line of evolution, Euarchontoglires, led to present-day primates, tree shrews, flying lemurs, rodents and rabbits. Early primates evolved from small-brained, nocturnal, insect-eating mammals with an expanded region of temporal visual cortex. These early nocturnal primates were adapted to the fine branch niche of the tropical rainforest by having an even more expanded visual system that mediated visually guided reaching and grasping of insects, small vertebrates, and fruits. Neocortex was greatly expanded, and included an array of cortical areas that characterize neocortex of all living primates. Specializations of the visual system included new visual areas that contributed to a dorsal stream of visuomotor processing in a

  6. The Evolution of Brains from Early Mammals to Humans

    PubMed Central

    Kaas, Jon H.

    2012-01-01

    The large size and complex organization of the human brain makes it unique among primate brains. In particular, the neocortex constitutes about 80% of the brain, and this cortex is subdivided into a large number of functionally specialized regions, the cortical areas. Such a brain mediates accomplishments and abilities unmatched by any other species. How did such a brain evolve? Answers come from comparative studies of the brains of present-day mammals and other vertebrates in conjunction with information about brain sizes and shapes from the fossil record, studies of brain development, and principles derived from studies of scaling and optimal design. Early mammals were small, with small brains, an emphasis on olfaction, and little neocortex. Neocortex was transformed from the single layer of output pyramidal neurons of the dorsal cortex of earlier ancestors to the six layers of all present-day mammals. This small cap of neocortex was divided into 20–25 cortical areas, including primary and some of the secondary sensory areas that characterize neocortex in nearly all mammals today. Early placental mammals had a corpus callosum connecting the neocortex of the two hemispheres, a primary motor area, M1, and perhaps one or more premotor areas. One line of evolution, Euarchontoglires, led to present-day primates, tree shrews, flying lemurs, rodents and rabbits. Early primates evolved from small-brained, nocturnal, insect-eating mammals with an expanded region of temporal visual cortex. These early nocturnal primates were adapted to the fine branch niche of the tropical rainforest by having an even more expanded visual system that mediated visually guided reaching and grasping of insects, small vertebrates, and fruits. Neocortex was greatly expanded, and included an array of cortical areas that characterize neocortex of all living primates. Specializations of the visual system included new visual areas that contributed to a dorsal stream of visuomotor processing in a

  7. Spatial Localization of Recent Ancestors for Admixed Individuals

    PubMed Central

    Yang, Wen-Yun; Platt, Alexander; Chiang, Charleston Wen-Kai; Eskin, Eleazar; Novembre, John; Pasaniuc, Bogdan

    2014-01-01

    Ancestry analysis from genetic data plays a critical role in studies of human disease and evolution. Recent work has introduced explicit models for the geographic distribution of genetic variation and has shown that such explicit models yield superior accuracy in ancestry inference over nonmodel-based methods. Here we extend such work to introduce a method that models admixture between ancestors from multiple sources across a geographic continuum. We devise efficient algorithms based on hidden Markov models to localize on a map the recent ancestors (e.g., grandparents) of admixed individuals, joint with assigning ancestry at each locus in the genome. We validate our methods by using empirical data from individuals with mixed European ancestry from the Population Reference Sample study and show that our approach is able to localize their recent ancestors within an average of 470 km of the reported locations of their grandparents. Furthermore, simulations from real Population Reference Sample genotype data show that our method attains high accuracy in localizing recent ancestors of admixed individuals in Europe (an average of 550 km from their true location for localization of two ancestries in Europe, four generations ago). We explore the limits of ancestry localization under our approach and find that performance decreases as the number of distinct ancestries and generations since admixture increases. Finally, we build a map of expected localization accuracy across admixed individuals according to the location of origin within Europe of their ancestors. PMID:25371484

  8. Magnetochronology of early humans in China

    NASA Astrophysics Data System (ADS)

    Deng, C.; Zhu, R.; Pan, Y.

    2009-12-01

    China is a key area for probing into human occupation in the Old World after the initial expansion of early humans out of Africa. Chronology of Chinese Paleolithic/hominin sites in different paleoclimatic and paleoenvironmental settings is paramount for understanding early human migration and adaptation. In recent years, we conducted detailed magnetostratigraphic investigations on the Nihewan Basin in temperate northern China and the Yuanmou Basin in subtropical southern China, both of which contained abundant sites of early humans and mammalian faunas. The age of the sedimentary sequence of the eastern Nihewan Basin can be magnetostratigraphically constrained to an interval from late Pliocene to late Pleistocene. The basal age of the Nihewan Formation in the eastern basin is constrained just prior to the Gauss-Matuyama geomagnetic reversal, that is, between ~2.6 Ma and ~3.0 Ma. The fluvio-lacustrine sequences in this basin were deposited from the late Gauss chron into the late Brunhes chron, and are capped by the last interglacial soil and the last glacial loess , or by the late Pleistocene or Holocene loess sediments. As a result, the Nihewan faunas (sensu lato) can be placed between the Matuyama-Brunhes geomagnetic reversal and the onset of the Olduvai subchron (0.78-1.95 Ma), and a robust chronological sequence of early human colonization in this basin has been established: Maliang (0.8 Ma), Huojiadi (1.0 Ma), Donggutuo and Cenjiawan (1.1 Ma), Feiliang (1.2 Ma), Banshan (1.32 Ma), Xiaochangliang and Xiantai (1.36 Ma), MJG-I (1.55 Ma), MJG-II (1.64 Ma), and MJG-III (1.66 Ma). The age of the sedimentary sequence of the Yuanmou Basin can be magnetostratigraphically constrained to an interval from early Pliocene to Pleistocene. The basal age of this basin sedimentary sequence is constrained just prior to the onset of the Sidufjall subchron, that is, ~4.9 Ma. Accumulation of the Yuanmou sequence was terminated during the Matuyama chron bracketed by the Olduvai and

  9. The Hunt for Dwarf Galaxies' Ancestors

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Dwarf galaxies are typically very faint, and are therefore hard to find. Given that, what are our chances of finding their distant ancestors, located billions of light-years away? A recent study aims to find out.Ancient CounterpartsDwarf galaxies are a hot topic right now, especially as we discover more and more of them nearby. Besides being great places to investigate a variety of astrophysical processes, local group dwarf galaxies are also representative of the most common type of galaxy in the universe. For many of these dwarf galaxies, their low masses and typically old stellar populations suggest that most of their stars were formed early in the universes history, and further star formation was suppressed when the universe was reionized at redshifts of z ~ 610. If this is true, most dwarf galaxies are essentially fossils: theyve evolved little since that point.To test this theory, wed like to find counterparts to our local group dwarf galaxies at these higher redshifts of z = 6 or 7. But dwarf galaxies, since they dont exhibit lots of active star formation, have very low surface brightnesses making them very difficult to detect. What are the chances that current or future telescope sensitivities will allow us to detect these? Thats the question Anna Patej and Abraham Loeb, two theorists at Harvard University, have addressed in a recent study.Entering a New RegimeThe surface brightness vs. size for 73 local dwarf galaxies scaled back to redshifts of z=6 (top) and z=7 (bottom). So far weve been able to observe high-redshift galaxies within the boxed region of the parameter space. JWST will open the shaded region of the parameter space, which includes some of the dwarf galaxies. [Patej Loeb 2015]Starting from observational data for 87 Local-Group dwarf galaxies, Patej and Loeb used a stellar population synthesis code to evolve the galaxies backward in time to redshifts of z = 6 and 7. Next, they narrowed this sample to only those dwarfs for which most star

  10. Magnetostratigraphic dating of early humans in China

    NASA Astrophysics Data System (ADS)

    Zhu, Rixiang; An, Zhisheng; Potts, Richard; Hoffman, Kenneth A.

    2003-06-01

    China is a key area for research into human occupation in the Old World after the initial expansion of early humans out of Africa. Reliable age determinations are pivotal for assessing the patterns of human evolution and dispersal in this region. This paper reviews magnetostratigraphic studies of some early Pleistocene strata bearing hominin remains and/or artifact stone tools from northern to southern China. The quality and reliability of the paleomagnetic dates are also evaluated. New magnetostratigraphic results for the Xihoudu Paleolithic site in north-central China are also presented. Among the few hominin or Paleolithic sites in China from the early Pleistocene, five have been well investigated. Three of these are in northern China at Xiaochangliang, Donggutuo and Gongwangling; the remaining two in southern China at Longgupo and Yuanmou. Considerable progress has been made during the past three decades towards paleomagnetically dating these sites. Indeed, the age estimates at Xiaochangliang and Gongwangling have been widely accepted. Magnetostratigraphic consensus about the age of the Donggutuo site has also been reached. However, the age determination for the two sites in southern China is still contested. The integration of rock-magnetic stratigraphy with magnetic polarity stratigraphy has resulted in a determined age of 1.36 Ma for a stone tool-containing layer of lacustrine sediments at the Xiaochangliang site in the Nihewan Basin. Lithostratigraphic constraints have significantly contributed to determining the age of Lantian Homo erectus at Gongwangling, which occurred in a loess-paleosol sequence of the southern Loess Plateau. Its age, paleomagnetically derived, is about 1.15 Ma. These two paleomagnetic ages suggest an expansion and flourishing of human groups from northern to north-central China during the early Pleistocene. This suggestion has been reinforced by our new magnetostratigraphic age estimate of about 1.27 Ma for the Xihoudu site as will be

  11. The Five Ancestors--Book 1: Tiger

    ERIC Educational Resources Information Center

    Stone, Jeff

    2004-01-01

    Losing a job is an awfully low point--until it turns into the opportunity to pursue writing full time, and a book like "The Five Ancestors: Tiger" results. Jeff Stone looks back to his own experience as a young reader and taps that experience to help frame his own writing. An intriguing snapshot of his new book follows.

  12. Apparatus Named after Our Academic Ancestors, III

    ERIC Educational Resources Information Center

    Greenslade, Thomas B., Jr.

    2014-01-01

    My academic ancestors in physics have called on me once more to tell you about the apparatus that they devised, and that many of you have used in your demonstrations and labs. This article is about apparatus named after François Arago, Heinrich Helmholtz, Leon Foucault, and James Watt.

  13. Apparatus Named After Our Academic Ancestors, III

    NASA Astrophysics Data System (ADS)

    Greenslade, Thomas B.

    2014-09-01

    My academic ancestors in physics have called on me once more to tell you about the apparatus that they devised, and that many of you have used in your demonstrations and labs. This article is about apparatus named after François Arago, Heinrich Helmholtz, Leon Foucault, and James Watt.

  14. Gazing Back: Communing with Our Ancestors

    ERIC Educational Resources Information Center

    Osorio, Jonathan Kay Kamakawiwo'ole

    2004-01-01

    This article is a poignant commentary on the connection of the Native Hawaiian people with the past, the present, and the future. In this article, the author positions himself within the histories of his people. He talks about putting faces to his ancestors by linking them with the people of his day, and he talks about reconstructing the…

  15. Skeletal variation among early Holocene North American humans: implications for origins and diversity in the Americas.

    PubMed

    Auerbach, Benjamin M

    2012-12-01

    The movement of humans into the Americas remains a major topic of debate among scientific disciplines. Central to this discussion is ascertaining the timing and migratory routes of the earliest colonizers, in addition to understanding their ancestry. Molecular studies have recently argued that the colonizing population was isolated from other Asian populations for an extended period before proceeding to colonize the Americas. This research has suggested that Beringia was the location of this "incubation," though archaeological and skeletal data have not yet supported this hypothesis. This study employs the remains of the five most complete North American male early Holocene skeletons to examine patterns of human morphology at the earliest observable time period. Stature, body mass, body breadth, and limb proportions are examined in the context of male skeletal samples representing the range of morphological variation in North America in the last two millennia of the Holocene. These are also compared with a global sample. Results indicate that early Holocene males have variable postcranial morphologies, but all share the common trait of wide bodies. This trait, which is retained in more recent indigenous North American groups, is associated with adaptations to cold climates. Peoples from the Americas exhibit wider bodies than other populations sampled globally. This pattern suggests the common ancestral population of all of these indigenous American groups had reduced morphological variation in this trait. Furthermore, this provides support for a single, possibly high latitude location for the genetic isolation of ancestors of the human colonizers of the Americas.

  16. Redeeming the lost voice of the ancestors.

    PubMed

    Troudart, Michal

    2012-09-01

    The Holocaust of the Jews in World War II involved not only the murder of 6 million Jews but also the traumatic destruction and wipe-out of whole communities, with their rich culture and tradition which had existed for centuries. In places where no one survived, it was almost impossible to reconstruct the collective memory of those communities. The voice of the ancestors was lost. As a daughter of Holocaust survivors, I have always felt the strong presence of the loss, not only of the murdered family members but also of the ancient colourful world of Eastern European Jews. I have always felt compelled to link back to that lost world. In the past three years, my journey to the pre-war past has become more intense. This article describes the double role of my journey: it is both an attempt to reconstruct, redeem and preserve the memory of the lost ancestors, and a personal journey to the echoes of my ancestors' voices within my soul.

  17. Mitochondrial lineage M1 traces an early human backflow to Africa

    PubMed Central

    González, Ana M; Larruga, José M; Abu-Amero, Khaled K; Shi, Yufei; Pestano, José; Cabrera, Vicente M

    2007-01-01

    Background The out of Africa hypothesis has gained generalized consensus. However, many specific questions remain unsettled. To know whether the two M and N macrohaplogroups that colonized Eurasia were already present in Africa before the exit is puzzling. It has been proposed that the east African clade M1 supports a single origin of haplogroup M in Africa. To test the validity of that hypothesis, the phylogeographic analysis of 13 complete mitochondrial DNA (mtDNA) sequences and 261 partial sequences belonging to haplogroup M1 was carried out. Results The coalescence age of the African haplogroup M1 is younger than those for other M Asiatic clades. In contradiction to the hypothesis of an eastern Africa origin for modern human expansions out of Africa, the most ancestral M1 lineages have been found in Northwest Africa and in the Near East, instead of in East Africa. The M1 geographic distribution and the relative ages of its different subclades clearly correlate with those of haplogroup U6, for which an Eurasian ancestor has been demonstrated. Conclusion This study provides evidence that M1, or its ancestor, had an Asiatic origin. The earliest M1 expansion into Africa occurred in northwestern instead of eastern areas; this early spread reached the Iberian Peninsula even affecting the Basques. The majority of the M1a lineages found outside and inside Africa had a more recent eastern Africa origin. Both western and eastern M1 lineages participated in the Neolithic colonization of the Sahara. The striking parallelism between subclade ages and geographic distribution of M1 and its North African U6 counterpart strongly reinforces this scenario. Finally, a relevant fraction of M1a lineages present today in the European Continent and nearby islands possibly had a Jewish instead of the commonly proposed Arab/Berber maternal ascendance. PMID:17620140

  18. Punctuated emergences of genetic and phenotypic innovations in eumetazoan, bilaterian, euteleostome, and hominidae ancestors.

    PubMed

    Wenger, Yvan; Galliot, Brigitte

    2013-01-01

    Phenotypic traits derive from the selective recruitment of genetic materials over macroevolutionary times, and protein-coding genes constitute an essential component of these materials. We took advantage of the recent production of genomic scale data from sponges and cnidarians, sister groups from eumetazoans and bilaterians, respectively, to date the emergence of human proteins and to infer the timing of acquisition of novel traits through metazoan evolution. Comparing the proteomes of 23 eukaryotes, we find that 33% human proteins have an ortholog in nonmetazoan species. This premetazoan proteome associates with 43% of all annotated human biological processes. Subsequently, four major waves of innovations can be inferred in the last common ancestors of eumetazoans, bilaterians, euteleostomi (bony vertebrates), and hominidae, largely specific to each epoch, whereas early branching deuterostome and chordate phyla show very few innovations. Interestingly, groups of proteins that act together in their modern human functions often originated concomitantly, although the corresponding human phenotypes frequently emerged later. For example, the three cnidarians Acropora, Nematostella, and Hydra express a highly similar protein inventory, and their protein innovations can be affiliated either to traits shared by all eumetazoans (gut differentiation, neurogenesis); or to bilaterian traits present in only some cnidarians (eyes, striated muscle); or to traits not identified yet in this phylum (mesodermal layer, endocrine glands). The variable correspondence between phenotypes predicted from protein enrichments and observed phenotypes suggests that a parallel mechanism repeatedly produce similar phenotypes, thanks to novel regulatory events that independently tie preexisting conserved genetic modules.

  19. Punctuated Emergences of Genetic and Phenotypic Innovations in Eumetazoan, Bilaterian, Euteleostome, and Hominidae Ancestors

    PubMed Central

    Wenger, Yvan; Galliot, Brigitte

    2013-01-01

    Phenotypic traits derive from the selective recruitment of genetic materials over macroevolutionary times, and protein-coding genes constitute an essential component of these materials. We took advantage of the recent production of genomic scale data from sponges and cnidarians, sister groups from eumetazoans and bilaterians, respectively, to date the emergence of human proteins and to infer the timing of acquisition of novel traits through metazoan evolution. Comparing the proteomes of 23 eukaryotes, we find that 33% human proteins have an ortholog in nonmetazoan species. This premetazoan proteome associates with 43% of all annotated human biological processes. Subsequently, four major waves of innovations can be inferred in the last common ancestors of eumetazoans, bilaterians, euteleostomi (bony vertebrates), and hominidae, largely specific to each epoch, whereas early branching deuterostome and chordate phyla show very few innovations. Interestingly, groups of proteins that act together in their modern human functions often originated concomitantly, although the corresponding human phenotypes frequently emerged later. For example, the three cnidarians Acropora, Nematostella, and Hydra express a highly similar protein inventory, and their protein innovations can be affiliated either to traits shared by all eumetazoans (gut differentiation, neurogenesis); or to bilaterian traits present in only some cnidarians (eyes, striated muscle); or to traits not identified yet in this phylum (mesodermal layer, endocrine glands). The variable correspondence between phenotypes predicted from protein enrichments and observed phenotypes suggests that a parallel mechanism repeatedly produce similar phenotypes, thanks to novel regulatory events that independently tie preexisting conserved genetic modules. PMID:24065732

  20. Technical comment on "The placental mammal ancestor and the post-K-Pg radiation of placentals".

    PubMed

    Springer, Mark S; Meredith, Robert W; Teeling, Emma C; Murphy, William J

    2013-08-01

    O'Leary et al. (Research Article, 8 February 2013, p. 662) examined mammalian relationships and divergence times and concluded that a single placental ancestor crossed the Cretaceous-Paleogene (K-Pg) boundary. This conclusion relies on phylogenetic analyses that fail to discriminate between homology and homoplasy and further implies virus-like rates of nucleotide substitution in early Paleocene placentals. PMID:23929967

  1. Teleoperation support for early human planetary missions.

    PubMed

    Genta, Giancarlo; Perino, Maria Antonietta

    2005-12-01

    A renewed interest in human exploration is flourishing among all the major spacefaring nations. In fact, in the complex scene of planned future space activities, the development of a Moon base and the human exploration of Mars might have the potential to renew the enthusiasm in expanding the human presence beyond the boundaries of Earth. Various initiatives have been undertaken to define scenarios and identify the required infrastructures and related technology innovations. The typical proposed approach follows a multistep strategy, starting with a series of precursor robotic missions to acquire further knowledge of the planet and to select the best potential landing sites, and evolving toward more demanding missions for the development of a surface infrastructure necessary to sustain human presence. The technologies involved in such a demanding enterprise range from typical space technologies, like transportation and propulsion, automation and robotics, rendezvous and docking, entry/reentry, aero-braking, navigation, and deep space communications, to human-specific issues like physiology, psychology, behavioral aspects, and nutritional science for long-duration exposure, that go beyond the traditional boundaries of space activities. Among the required elements to support planetary exploration, both for the precursor robotic missions and to sustain human exploration, rovers and trucks play a key role. A robust level of autonomy will need to be secured to perform preplanned operations, particularly for the surface infrastructure development, and a teleoperated support, either from Earth or from a local base, will enhance the in situ field exploration capability.

  2. Continuity or discontinuity in the European Early Pleistocene human settlement: the Atapuerca evidence

    NASA Astrophysics Data System (ADS)

    Bermúdez de Castro, José María; Martinón-Torres, María; Blasco, Ruth; Rosell, Jordi; Carbonell, Eudald

    2013-09-01

    The nature, timing, pattern, favourable circumstances and impediments of the human occupation of the European continent during the Early Pleistocene are hot topics in Quaternary studies. In particular, the problem of the (dis) continuity of the settlement of Europe in this period is an important matter of discussion, which has been approached in the last decade from different points of view. The Gran Dolina (TD) and Sima del Elefante (TE) cave sites in the Sierra de Atapuerca, (Spain) include large and quasi-continuous stratigraphic sequences that stretch back from at least 1.2 million years ago (Ma) to the Matuyama/Brunhes boundary. The archaeological and paleontological record from these sites can help to test different hypotheses about the character of the human settlement in this region and period. Furthermore, the TD6 level has yielded a large collection of human fossil remains attributed to Homo antecessor. According to different geochronological methods, as well as to paleomagnetic and biostratigraphical analyses, these hominins belong to an age range of 0.96-0.80 Ma. Unfortunately, the finding in 2007 of some human fossil remains in the TE9 level, dated to about 1.22 Ma, was not enough to conclude whether H. antecessor had deep roots in the European Early Pleistocene. A set of derived features of H. antecessor shared with both the Neanderthal lineage and modern humans suggests that this species is related, and not far, from the most recent common ancestor (MRCA) of Homo neanderthalensis and Homo sapiens. If we assume that there was a lineal biological relationship between the TE9 and TD6 hominins, we should reconsider many of the conclusions achieved in previous paleontological and genetic studies. In addition, we would be obliged to build a highly complicated paleogeographical scenario for the origin of the MRCA. Although continuity in the settlement of Europe during the entire late Early Pleistocene is not discarded (e.g. in refuge areas), it seems that

  3. Young Children's Enactments of Human Rights in Early Childhood Education

    ERIC Educational Resources Information Center

    Quennerstedt, Ann

    2016-01-01

    This paper explores ways in which human rights become part of and affect young children's everyday practices in early childhood education and, more particularly, how very young children enact human rights in the preschool setting. The study is conducted in a Swedish preschool through observations of the everyday practices of a group of children…

  4. The existence and abundance of ghost ancestors in biparental populations.

    PubMed

    Gravel, Simon; Steel, Mike

    2015-05-01

    In a randomly-mating biparental population of size N there are, with high probability, individuals who are genealogical ancestors of every extant individual within approximately log2(N) generations into the past. We use this result of J. Chang to prove a curious corollary under standard models of recombination: there exist, with high probability, individuals within a constant multiple of log2(N) generations into the past who are simultaneously (i) genealogical ancestors of each of the individuals at the present, and (ii) genetic ancestors to none of the individuals at the present. Such ancestral individuals-ancestors of everyone today that left no genetic trace-represent 'ghost' ancestors in a strong sense. In this short note, we use simple analytical argument and simulations to estimate how many such individuals exist in finite Wright-Fisher populations. PMID:25703300

  5. Neurochemical changes within human early blind occipital cortex.

    PubMed

    Weaver, K E; Richards, T L; Saenz, M; Petropoulos, H; Fine, I

    2013-11-12

    Early blindness results in occipital cortex neurons responding to a wide range of auditory and tactile stimuli. These changes in tuning properties are accompanied by an extensive reorganization of the occipital cortex that includes alterations in anatomical structure, neurochemical and metabolic pathways. Although it has been established in animal models that neurochemical pathways are heavily affected by early visual deprivation, the effects of blindness on these pathways in humans is still not well characterized. Here, using (1)H magnetic resonance spectroscopy in nine early blind and normally sighted subjects, we find that early blindness is associated with higher levels of creatine, choline and myo-Inositol and indications of lower levels of GABA within the occipital cortex. These results suggest that the cross-modal responses associated with early blindness may, at least in part, be driven by changes within occipital biochemical pathways.

  6. The physiology and habitat of the last universal common ancestor.

    PubMed

    Weiss, Madeline C; Sousa, Filipa L; Mrnjavac, Natalia; Neukirchen, Sinje; Roettger, Mayo; Nelson-Sathi, Shijulal; Martin, William F

    2016-01-01

    The concept of a last universal common ancestor of all cells (LUCA, or the progenote) is central to the study of early evolution and life's origin, yet information about how and where LUCA lived is lacking. We investigated all clusters and phylogenetic trees for 6.1 million protein coding genes from sequenced prokaryotic genomes in order to reconstruct the microbial ecology of LUCA. Among 286,514 protein clusters, we identified 355 protein families (∼0.1%) that trace to LUCA by phylogenetic criteria. Because these proteins are not universally distributed, they can shed light on LUCA's physiology. Their functions, properties and prosthetic groups depict LUCA as anaerobic, CO2-fixing, H2-dependent with a Wood-Ljungdahl pathway, N2-fixing and thermophilic. LUCA's biochemistry was replete with FeS clusters and radical reaction mechanisms. Its cofactors reveal dependence upon transition metals, flavins, S-adenosyl methionine, coenzyme A, ferredoxin, molybdopterin, corrins and selenium. Its genetic code required nucleoside modifications and S-adenosyl methionine-dependent methylations. The 355 phylogenies identify clostridia and methanogens, whose modern lifestyles resemble that of LUCA, as basal among their respective domains. LUCA inhabited a geochemically active environment rich in H2, CO2 and iron. The data support the theory of an autotrophic origin of life involving the Wood-Ljungdahl pathway in a hydrothermal setting. PMID:27562259

  7. Algal ancestor of land plants was preadapted for symbiosis.

    PubMed

    Delaux, Pierre-Marc; Radhakrishnan, Guru V; Jayaraman, Dhileepkumar; Cheema, Jitender; Malbreil, Mathilde; Volkening, Jeremy D; Sekimoto, Hiroyuki; Nishiyama, Tomoaki; Melkonian, Michael; Pokorny, Lisa; Rothfels, Carl J; Sederoff, Heike Winter; Stevenson, Dennis W; Surek, Barbara; Zhang, Yong; Sussman, Michael R; Dunand, Christophe; Morris, Richard J; Roux, Christophe; Wong, Gane Ka-Shu; Oldroyd, Giles E D; Ané, Jean-Michel

    2015-10-27

    Colonization of land by plants was a major transition on Earth, but the developmental and genetic innovations required for this transition remain unknown. Physiological studies and the fossil record strongly suggest that the ability of the first land plants to form symbiotic associations with beneficial fungi was one of these critical innovations. In angiosperms, genes required for the perception and transduction of diffusible fungal signals for root colonization and for nutrient exchange have been characterized. However, the origin of these genes and their potential correlation with land colonization remain elusive. A comprehensive phylogenetic analysis of 259 transcriptomes and 10 green algal and basal land plant genomes, coupled with the characterization of the evolutionary path leading to the appearance of a key regulator, a calcium- and calmodulin-dependent protein kinase, showed that the symbiotic signaling pathway predated the first land plants. In contrast, downstream genes required for root colonization and their specific expression pattern probably appeared subsequent to the colonization of land. We conclude that the most recent common ancestor of extant land plants and green algae was preadapted for symbiotic associations. Subsequent improvement of this precursor stage in early land plants through rounds of gene duplication led to the acquisition of additional pathways and the ability to form a fully functional arbuscular mycorrhizal symbiosis. PMID:26438870

  8. Mexican papita viroid: putative ancestor of crop viroids.

    PubMed Central

    Martínez-Soriano, J P; Galindo-Alonso, J; Maroon, C J; Yucel, I; Smith, D R; Diener, T O

    1996-01-01

    The potato spindle tuber disease was first observed early in the 20th century in the northeastern United States and shown, in 1971, to be incited by a viroid, potato spindle tuber viroid (PSTVd). No wild-plant PSTVd reservoirs have been identified; thus, the initial source of PSTVd infecting potatoes has remained a mystery. Several variants of a novel viroid, designated Mexican papita viroid (MPVd), have now been isolated from Solanum cardiophyllum Lindl. (papita güera, cimantli) plants growing wild in the Mexican state of Aguascalientes. MPVd's nucleotide sequence is most closely related to those of the tomato planta macho viroid (TPMVd) and PSTVd. From TPMVd, MPVd may be distinguished on the basis of biological properties, such as replication and symptom formation in certain differential hosts. Phylogenetic and ecological data indicate that MPVd and certain viroids now affecting crop plants, such as TPMVd, PSTVd, and possibly others, have a common ancestor. We hypothesize that commercial potatoes grown in the United States have become viroid-infected by chance transfer of MPVd or a similar viroid from endemically infected wild solanaceous plants imported from Mexico as germplasm, conceivably from plants known to have been introduced from Mexico to the United States late in the 19th century in efforts to identify genetic resistance to the potato late blight fungus, Phytophthora infestans. Images Fig. 1 PMID:8790341

  9. Algal ancestor of land plants was preadapted for symbiosis

    PubMed Central

    Delaux, Pierre-Marc; Radhakrishnan, Guru V.; Jayaraman, Dhileepkumar; Cheema, Jitender; Malbreil, Mathilde; Volkening, Jeremy D.; Sekimoto, Hiroyuki; Nishiyama, Tomoaki; Melkonian, Michael; Pokorny, Lisa; Rothfels, Carl J.; Sederoff, Heike Winter; Stevenson, Dennis W.; Surek, Barbara; Zhang, Yong; Sussman, Michael R.; Dunand, Christophe; Morris, Richard J.; Roux, Christophe; Wong, Gane Ka-Shu; Oldroyd, Giles E. D.; Ané, Jean-Michel

    2015-01-01

    Colonization of land by plants was a major transition on Earth, but the developmental and genetic innovations required for this transition remain unknown. Physiological studies and the fossil record strongly suggest that the ability of the first land plants to form symbiotic associations with beneficial fungi was one of these critical innovations. In angiosperms, genes required for the perception and transduction of diffusible fungal signals for root colonization and for nutrient exchange have been characterized. However, the origin of these genes and their potential correlation with land colonization remain elusive. A comprehensive phylogenetic analysis of 259 transcriptomes and 10 green algal and basal land plant genomes, coupled with the characterization of the evolutionary path leading to the appearance of a key regulator, a calcium- and calmodulin-dependent protein kinase, showed that the symbiotic signaling pathway predated the first land plants. In contrast, downstream genes required for root colonization and their specific expression pattern probably appeared subsequent to the colonization of land. We conclude that the most recent common ancestor of extant land plants and green algae was preadapted for symbiotic associations. Subsequent improvement of this precursor stage in early land plants through rounds of gene duplication led to the acquisition of additional pathways and the ability to form a fully functional arbuscular mycorrhizal symbiosis. PMID:26438870

  10. Algal ancestor of land plants was preadapted for symbiosis.

    PubMed

    Delaux, Pierre-Marc; Radhakrishnan, Guru V; Jayaraman, Dhileepkumar; Cheema, Jitender; Malbreil, Mathilde; Volkening, Jeremy D; Sekimoto, Hiroyuki; Nishiyama, Tomoaki; Melkonian, Michael; Pokorny, Lisa; Rothfels, Carl J; Sederoff, Heike Winter; Stevenson, Dennis W; Surek, Barbara; Zhang, Yong; Sussman, Michael R; Dunand, Christophe; Morris, Richard J; Roux, Christophe; Wong, Gane Ka-Shu; Oldroyd, Giles E D; Ané, Jean-Michel

    2015-10-27

    Colonization of land by plants was a major transition on Earth, but the developmental and genetic innovations required for this transition remain unknown. Physiological studies and the fossil record strongly suggest that the ability of the first land plants to form symbiotic associations with beneficial fungi was one of these critical innovations. In angiosperms, genes required for the perception and transduction of diffusible fungal signals for root colonization and for nutrient exchange have been characterized. However, the origin of these genes and their potential correlation with land colonization remain elusive. A comprehensive phylogenetic analysis of 259 transcriptomes and 10 green algal and basal land plant genomes, coupled with the characterization of the evolutionary path leading to the appearance of a key regulator, a calcium- and calmodulin-dependent protein kinase, showed that the symbiotic signaling pathway predated the first land plants. In contrast, downstream genes required for root colonization and their specific expression pattern probably appeared subsequent to the colonization of land. We conclude that the most recent common ancestor of extant land plants and green algae was preadapted for symbiotic associations. Subsequent improvement of this precursor stage in early land plants through rounds of gene duplication led to the acquisition of additional pathways and the ability to form a fully functional arbuscular mycorrhizal symbiosis.

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

    PubMed

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

    2005-05-19

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

  12. Locomotion and posture from the common hominoid ancestor to fully modern hominins, with special reference to the last common panin/hominin ancestor.

    PubMed

    Crompton, R H; Vereecke, E E; Thorpe, S K S

    2008-04-01

    Based on our knowledge of locomotor biomechanics and ecology we predict the locomotion and posture of the last common ancestors of (a) great and lesser apes and their close fossil relatives (hominoids); (b) chimpanzees, bonobos and modern humans (hominines); and (c) modern humans and their fossil relatives (hominins). We evaluate our propositions against the fossil record in the context of a broader review of evolution of the locomotor system from the earliest hominoids of modern aspect (crown hominoids) to early modern Homo sapiens. While some early East African stem hominoids were pronograde, it appears that the adaptations which best characterize the crown hominoids are orthogrady and an ability to abduct the arm above the shoulder - rather than, as is often thought, manual suspension sensu stricto. At 7-9 Ma (not much earlier than the likely 4-8 Ma divergence date for panins and hominins, see Bradley, 2008) there were crown hominoids in southern Europe which were adapted to moving in an orthograde posture, supported primarily on the hindlimb, in an arboreal, and possibly for Oreopithecus, a terrestrial context. By 7 Ma, Sahelanthropus provides evidence of a Central African hominin, panin or possibly gorilline adapted to orthogrady, and both orthogrady and habitually highly extended postures of the hip are evident in the arboreal East African protohominin Orrorin at 6 Ma. If the traditional idea that hominins passed through a terrestrial 'knuckle-walking' phase is correct, not only does it have to be explained how a quadrupedal gait typified by flexed postures of the hindlimb could have preadapted the body for the hominin acquisition of straight-legged erect bipedality, but we would have to accept a transition from stem-hominoid pronogrady to crown hominoid orthogrady, back again to pronogrady in the African apes and then back to orthogrady in hominins. Hand-assisted arboreal bipedality, which is part of a continuum of orthograde behaviours, is used by modern

  13. Locomotion and posture from the common hominoid ancestor to fully modern hominins, with special reference to the last common panin/hominin ancestor

    PubMed Central

    Crompton, R H; Vereecke, E E; Thorpe, S K S

    2008-01-01

    Based on our knowledge of locomotor biomechanics and ecology we predict the locomotion and posture of the last common ancestors of (a) great and lesser apes and their close fossil relatives (hominoids); (b) chimpanzees, bonobos and modern humans (hominines); and (c) modern humans and their fossil relatives (hominins). We evaluate our propositions against the fossil record in the context of a broader review of evolution of the locomotor system from the earliest hominoids of modern aspect (crown hominoids) to early modern Homo sapiens. While some early East African stem hominoids were pronograde, it appears that the adaptations which best characterize the crown hominoids are orthogrady and an ability to abduct the arm above the shoulder – rather than, as is often thought, manual suspension sensu stricto. At 7–9 Ma (not much earlier than the likely 4–8 Ma divergence date for panins and hominins, see Bradley, 2008) there were crown hominoids in southern Europe which were adapted to moving in an orthograde posture, supported primarily on the hindlimb, in an arboreal, and possibly for Oreopithecus, a terrestrial context. By 7 Ma, Sahelanthropus provides evidence of a Central African hominin, panin or possibly gorilline adapted to orthogrady, and both orthogrady and habitually highly extended postures of the hip are evident in the arboreal East African protohominin Orrorin at 6 Ma. If the traditional idea that hominins passed through a terrestrial ‘knuckle-walking’ phase is correct, not only does it have to be explained how a quadrupedal gait typified by flexed postures of the hindlimb could have preadapted the body for the hominin acquisition of straight-legged erect bipedality, but we would have to accept a transition from stem-hominoid pronogrady to crown hominoid orthogrady, back again to pronogrady in the African apes and then back to orthogrady in hominins. Hand-assisted arboreal bipedality, which is part of a continuum of orthograde behaviours, is used by

  14. Population Dynamics of Early Human Migration in Britain

    PubMed Central

    Vahia, Mayank N.; Ladiwala, Uma; Mahathe, Pavan; Mathur, Deepak

    2016-01-01

    Background Early human migration is largely determined by geography and human needs. These are both deterministic parameters when small populations move into unoccupied areas where conflicts and large group dynamics are not important. The early period of human migration into the British Isles provides such a laboratory which, because of its relative geographical isolation, may allow some insights into the complex dynamics of early human migration and interaction. Method and Results We developed a simulation code based on human affinity to habitable land, as defined by availability of water sources, altitude, and flatness of land, in choosing the path of migration. Movement of people on the British island over the prehistoric period from their initial entry points was simulated on the basis of data from the megalithic period. Topographical and hydro-shed data from satellite databases was used to define habitability, based on distance from water bodies, flatness of the terrain, and altitude above sea level. We simulated population movement based on assumptions of affinity for more habitable places, with the rate of movement tempered by existing populations. We compared results of our computer simulations with genetic data and show that our simulation can predict fairly accurately the points of contacts between different migratory paths. Such comparison also provides more detailed information about the path of peoples’ movement over ~2000 years before the present era. Conclusions We demonstrate an accurate method to simulate prehistoric movements of people based upon current topographical satellite data. Our findings are validated by recently-available genetic data. Our method may prove useful in determining early human population dynamics even when no genetic information is available. PMID:27148959

  15. Early development of synchrony in cortical activations in the human

    PubMed Central

    Koolen, N.; Dereymaeker, A.; Räsänen, O.; Jansen, K.; Vervisch, J.; Matic, V.; Naulaers, G.; De Vos, M.; Van Huffel, S.; Vanhatalo, S.

    2016-01-01

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. PMID:26876605

  16. Telomerase Activity is Downregulated Early During Human Brain Development

    PubMed Central

    Ishaq, Abbas; Hanson, Peter S.; Morris, Christopher M.; Saretzki, Gabriele

    2016-01-01

    Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6–19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw. PMID:27322326

  17. Indigenous Ways--Fruits of Our Ancestors

    ERIC Educational Resources Information Center

    Cohn, Itamar

    2011-01-01

    In this paper the human-nature relationship is recognized as a major field of interest and a platform of ideas linked with it is explored. A "new" source to inform an alternative paradigm for outdoor education is proposed; it is millennia old, has roots all over the globe and is a living, breathing, and evolving tradition--indigenous ways. While…

  18. Ancestor embryos: embryonic gametes and genetic parenthood.

    PubMed

    Watt, Helen

    2014-11-01

    The proposal for reproducing human generations in vitro raises the question to what extent parenthood is possible in embryos and to what extent human rights and interests are dependent on conscious awareness. This paper argues that the interest in not being made a parent non-consensually for the benefit of others persists throughout the lifespan of the individual human organism. We do not become genetic parents by learning that we are parents; rather, we discover (or fail to discover) an existing genetic relationship between our offspring and ourselves. The claim to genetic parenthood of an embryo used for reproduction in vitro is, if anything, clearer than the claim of the adult for whom gametes are derived via ips cells, in that an embryo's cells, unlike an adult's somatic cells, are already functionally geared to producing gametes (among other types of cell). An embryo used to make gametes that are used in reproduction is immediately and non-consensually made a genetic parent and to that extent is wronged whether or not the parent embryo survives-as some could survive-the harvesting of cells. All human individuals carry objective interests in benefits appropriate to the kind of being they are; these include the stake in not being made a parent without one's consent, whether posthumously or otherwise.

  19. Origins and early development of human body knowledge.

    PubMed

    Slaughter, Virginia; Heron, Michelle

    2004-01-01

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

  20. Origins and early development of human body knowledge.

    PubMed

    Slaughter, Virginia; Heron, Michelle

    2004-01-01

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

  1. The DNA methylation landscape of human early embryos.

    PubMed

    Guo, Hongshan; Zhu, Ping; Yan, Liying; Li, Rong; Hu, Boqiang; Lian, Ying; Yan, Jie; Ren, Xiulian; Lin, Shengli; Li, Junsheng; Jin, Xiaohu; Shi, Xiaodan; Liu, Ping; Wang, Xiaoye; Wang, Wei; Wei, Yuan; Li, Xianlong; Guo, Fan; Wu, Xinglong; Fan, Xiaoying; Yong, Jun; Wen, Lu; Xie, Sunney X; Tang, Fuchou; Qiao, Jie

    2014-07-31

    DNA methylation is a crucial element in the epigenetic regulation of mammalian embryonic development. However, its dynamic patterns have not been analysed at the genome scale in human pre-implantation embryos due to technical difficulties and the scarcity of required materials. Here we systematically profile the methylome of human early embryos from the zygotic stage through to post-implantation by reduced representation bisulphite sequencing and whole-genome bisulphite sequencing. We show that the major wave of genome-wide demethylation is complete at the 2-cell stage, contrary to previous observations in mice. Moreover, the demethylation of the paternal genome is much faster than that of the maternal genome, and by the end of the zygotic stage the genome-wide methylation level in male pronuclei is already lower than that in female pronuclei. The inverse correlation between promoter methylation and gene expression gradually strengthens during early embryonic development, reaching its peak at the post-implantation stage. Furthermore, we show that active genes, with the trimethylation of histone H3 at lysine 4 (H3K4me3) mark at the promoter regions in pluripotent human embryonic stem cells, are essentially devoid of DNA methylation in both mature gametes and throughout pre-implantation development. Finally, we also show that long interspersed nuclear elements or short interspersed nuclear elements that are evolutionarily young are demethylated to a milder extent compared to older elements in the same family and have higher abundance of transcripts, indicating that early embryos tend to retain higher residual methylation at the evolutionarily younger and more active transposable elements. Our work provides insights into the critical features of the methylome of human early embryos, as well as its functional relation to the regulation of gene expression and the repression of transposable elements.

  2. Proposed Ancestors of Phage Nucleic Acid Packaging Motors (and Cells)

    PubMed Central

    Serwer, Philip

    2011-01-01

    I present a hypothesis that begins with the proposal that abiotic ancestors of phage RNA and DNA packaging systems (and cells) include mobile shells with an internal, molecule-transporting cavity. The foundations of this hypothesis include the conjecture that current nucleic acid packaging systems have imprints from abiotic ancestors. The abiotic shells (1) initially imbibe and later also bind and transport organic molecules, thereby providing a means for producing molecular interactions that are links in the chain of events that produces ancestors to the first molecules that are both information carrying and enzymatically active, and (2) are subsequently scaffolds on which proteins assemble to form ancestors common to both shells of viral capsids and cell membranes. Emergence of cells occurs via aggregation and merger of shells and internal contents. The hypothesis continues by using proposed imprints of abiotic and biotic ancestors to deduce an ancestral thermal ratchet-based DNA packaging motor that subsequently evolves to integrate a DNA packaging ATPase that provides a power stroke. PMID:21994778

  3. Evidence in hand: recent discoveries and the early evolution of human manual manipulation.

    PubMed

    Kivell, Tracy L

    2015-11-19

    For several decades, it was largely assumed that stone tool use and production were abilities limited to the genus Homo. However, growing palaeontological and archaeological evidence, comparative extant primate studies, as well as results from methodological advancements in biomechanics and morphological analyses, have been gradually accumulating and now provide strong support for more advanced manual manipulative abilities and tool-related behaviours in pre-Homo hominins than has been traditionally recognized. Here, I review the fossil evidence related to early hominin dexterity, including the recent discoveries of relatively complete early hominin hand skeletons, and new methodologies that are providing a more holistic interpretation of hand function, and insight into how our early ancestors may have balanced the functional requirements of both arboreal locomotion and tool-related behaviours.

  4. Early stress and human behavioral development: emerging evolutionary perspectives.

    PubMed

    Del Giudice, M

    2014-08-01

    Stress experienced early in life exerts a powerful, lasting influence on development. Converging empirical findings show that stressful experiences become deeply embedded in the child's neurobiology, with an astonishing range of long-term effects on cognition, emotion, and behavior. In contrast with the prevailing view that such effects are the maladaptive outcomes of 'toxic' stress, adaptive models regard them as manifestations of evolved developmental plasticity. In this paper, I offer a brief introduction to adaptive models of early stress and human behavioral development, with emphasis on recent theoretical contributions and emerging concepts in the field. I begin by contrasting dysregulation models of early stress with their adaptive counterparts; I then introduce life history theory as a unifying framework, and review recent work on predictive adaptive responses (PARs) in human life history development. In particular, I discuss the distinction between forecasting the future state of the environment (external prediction) and forecasting the future state of the organism (internal prediction). Next, I present the adaptive calibration model, an integrative model of individual differences in stress responsivity based on life history concepts. I conclude by examining how maternal-fetal conflict may shape the physiology of prenatal stress and its adaptive and maladaptive effects on postnatal development. In total, I aim to show how theoretical work from evolutionary biology is reshaping the way we think about the role of stress in human development, and provide researchers with an up-to-date conceptual map of this fascinating and rapidly evolving field.

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

    PubMed Central

    Trinkaus, Erik

    2007-01-01

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

  6. Cortisol levels and very early pregnancy loss in humans

    PubMed Central

    Nepomnaschy, Pablo A.; Welch, Kathleen B.; McConnell, Daniel S.; Low, Bobbi S.; Strassmann, Beverly I.; England, Barry G.

    2006-01-01

    Maternal stress is commonly cited as an important risk factor for spontaneous abortion. For humans, however, there is little physiological evidence linking miscarriage to stress. This lack of evidence may be attributable to a paucity of research on maternal stress during the earliest gestational stages. Most human studies have focused on “clinical” pregnancy (>6 weeks after the last menstrual period). The majority of miscarriages, however, occur earlier, within the first 3 weeks after conception (≈5 weeks after the last menstrual period). Studies focused on clinical pregnancy thus miss the most critical period for pregnancy continuance. We examined the association between miscarriage and levels of maternal urinary cortisol during the first 3 weeks after conception. Pregnancies characterized by increased maternal cortisol during this period (within participant analyses) were more likely to result in spontaneous abortion (P < 0.05). This evidence links increased levels in this stress marker with a higher risk of early pregnancy loss in humans. PMID:16495411

  7. Phylogeny: a non-hyperthermophilic ancestor for bacteria.

    PubMed

    Brochier, Céline; Philippe, Hervé

    2002-05-16

    The first phyla that emerge in the tree of life based on ribosomal RNA (rRNA) sequences are hyperthermophilic, which led to the hypothesis that the universal ancestor, and possibly the original living organism, was hyperthermophilic. Here we reanalyse the bacterial phylogeny based on rRNA using a more reliable approach, and find that hyperthermophilic bacteria (such as Aquificales and Thermotogales) do not emerge first, suggesting that the Bacteria had a non-hyperthermophilic ancestor. It seems that Planctomycetales, a phylum with numerous peculiarities, could be the first emerging bacterial group.

  8. Identification and expression of a human cytomegalovirus early glycoprotein.

    PubMed Central

    Chang, C P; Vesole, D H; Nelson, J; Oldstone, M B; Stinski, M F

    1989-01-01

    A human cytomegalovirus early gene which possesses three temporally regulated promoters is located in the large unique component of the viral genome between 0.054 and 0.064 map units (C.-P. Chang, C.L. Malone, and M.F. Stinski, J. Virol. 63:281-290, 1989). This gene contains a major open reading frame (ORF) located 233 bases downstream of the cap site of an early unspliced RNA. The major ORF predicts a polypeptide of 17 kilodaltons (kDa) which contains a glycoproteinlike signal and anchor domains as well as potential N-glycosylation sites. Antisera were prepared against synthetic peptides derived from amino acid sequences within the major ORF. The antisera detected a viral glycoprotein of 48 kDa in infected cells and recognized the in vitro-translated 17-kDa protein early-gene product. The viral glycoprotein, designated gp48, was modified by N-linked glycans and possibly O-linked glycans. The synthesis of gp48 occurred in the absence of viral DNA replication but accumulated to the highest levels at late times after infection. Since gp48 was found in the virion, it is considered an early structural glycoprotein. Images PMID:2545908

  9. Diversity of the Human Skin Microbiome Early in Life

    PubMed Central

    Capone, Kimberly A; Dowd, Scot E; Stamatas, Georgios N; Nikolovski, Janeta

    2011-01-01

    Within days after birth, rapid surface colonization of infant skin coincides with significant functional changes. Gradual maturation of skin function, structure, and composition continues throughout the first years of life. Recent reports have revealed topographical and temporal variations in the adult skin microbiome. Here we address the question of how the human skin microbiome develops early in life. We show that the composition of cutaneous microbial communities evolves over the first year of life, showing increasing diversity with age. Although early colonization is dominated by Staphylococci, their significant decline contributes to increased population evenness by the end of the first year. Similar to what has been shown in adults, the composition of infant skin microflora appears to be site specific. In contrast to adults, we find that Firmicutes predominate on infant skin. Timely and proper establishment of healthy skin microbiome during this early period might have a pivotal role in denying access to potentially infectious microbes and could affect microbiome composition and stability extending into adulthood. Bacterial communities contribute to the establishment of cutaneous homeostasis and modulate inflammatory responses. Early microbial colonization is therefore expected to critically affect the development of the skin immune function. PMID:21697884

  10. Ecosystem variability and early human habitats in eastern Africa

    PubMed Central

    Magill, Clayton R.; Ashley, Gail M.; Freeman, Katherine H.

    2013-01-01

    The role of savannas during the course of early human evolution has been debated for nearly a century, in part because of difficulties in characterizing local ecosystems from fossil and sediment records. Here, we present high-resolution lipid biomarker and isotopic signatures for organic matter preserved in lake sediments at Olduvai Gorge during a key juncture in human evolution about 2.0 Ma—the emergence and dispersal of Homo erectus (sensu lato). Using published data for modern plants and soils, we construct a framework for ecological interpretations of stable carbon-isotope compositions (expressed as δ13C values) of lipid biomarkers from ancient plants. Within this framework, δ13C values for sedimentary leaf lipids and total organic carbon from Olduvai Gorge indicate recurrent ecosystem variations, where open C4 grasslands abruptly transitioned to closed C3 forests within several hundreds to thousands of years. Carbon-isotopic signatures correlate most strongly with Earth’s orbital geometry (precession), and tropical sea-surface temperatures are significant secondary predictors in partial regression analyses. The scale and pace of repeated ecosystem variations at Olduvai Gorge contrast with long-held views of directional or stepwise aridification and grassland expansion in eastern Africa during the early Pleistocene and provide a local perspective on environmental hypotheses of human evolution. PMID:23267092

  11. Ecosystem variability and early human habitats in eastern Africa.

    PubMed

    Magill, Clayton R; Ashley, Gail M; Freeman, Katherine H

    2013-01-22

    The role of savannas during the course of early human evolution has been debated for nearly a century, in part because of difficulties in characterizing local ecosystems from fossil and sediment records. Here, we present high-resolution lipid biomarker and isotopic signatures for organic matter preserved in lake sediments at Olduvai Gorge during a key juncture in human evolution about 2.0 Ma--the emergence and dispersal of Homo erectus (sensu lato). Using published data for modern plants and soils, we construct a framework for ecological interpretations of stable carbon-isotope compositions (expressed as δ(13)C values) of lipid biomarkers from ancient plants. Within this framework, δ(13)C values for sedimentary leaf lipids and total organic carbon from Olduvai Gorge indicate recurrent ecosystem variations, where open C(4) grasslands abruptly transitioned to closed C(3) forests within several hundreds to thousands of years. Carbon-isotopic signatures correlate most strongly with Earth's orbital geometry (precession), and tropical sea-surface temperatures are significant secondary predictors in partial regression analyses. The scale and pace of repeated ecosystem variations at Olduvai Gorge contrast with long-held views of directional or stepwise aridification and grassland expansion in eastern Africa during the early Pleistocene and provide a local perspective on environmental hypotheses of human evolution.

  12. The Human Microbiome. Early Life Determinant of Health Outcomes

    PubMed Central

    2014-01-01

    The development of new technologies to isolate and identify microbial genomes has markedly increased our understanding of the role of microbiomes in health and disease. The idea, first proposed as part of the hygiene hypothesis, that environmental microbes influence the developmental trajectories of the immune system in early life, has now been considerably extended and refined. The abundant microbiota present in mucosal surfaces, especially the gut, is actively selected by the host through complex receptor systems that respond differentially depending on the molecular patterns presented to mucosal cells. Germ-free mice are more likely to develop allergic airway inflammation and show alterations in normal motor control and anxiety. These effects can be reversed by neonatal microbial recolonization but remain unchanged if recolonization occurs in adults. What emerges from these recent studies is the discovery of a complex, major early environmental determinant of lifetime human phenotypes. To change the natural course of asthma, obesity, and other chronic inflammatory conditions, active manipulation of the extensive bacterial, phage, and fungal metagenomes present in mucosal surfaces may be required, specifically during the developing years. Domesticating the human microbiome and adapting it to our health needs may be a challenge akin to, but far more complex than, the one faced by humanity when a few dozen species of plants and animals were domesticated during the transition between hunter-gatherer and sedentary societies after the end of the Pleistocene era. PMID:24437411

  13. An early history of human breast cancer: West meets East

    PubMed Central

    Yan, Shou-He

    2013-01-01

    Cancer has been increasingly recognized as a global issue. This is especially true in countries like China, where cancer incidence has increased likely because of changes in environment and lifestyle. However, cancer is not a modern disease; early cases have been recorded in ancient medical books in the West and in China. Here, we provide a brief history of cancer, focusing on cancer of the breast, and review the etymology of ai, the Chinese character for cancer. Notable findings from both Western and Chinese traditional medicine are presented to give an overview of the most important, early contributors to our evolving understanding of human breast cancer. We also discuss the earliest historical documents to record patients with breast cancer. PMID:23958056

  14. Early indices of deviance detection in humans and animal models.

    PubMed

    Grimm, Sabine; Escera, Carles; Nelken, Israel

    2016-04-01

    Detecting unexpected stimuli in the environment is a critical function of the auditory system. Responses to unexpected "deviant" sounds are enhanced compared to responses to expected stimuli. At the human scalp, deviance detection is reflected in the mismatch negativity (MMN) and in an enhancement of the middle-latency response (MLR). Single neurons often respond more strongly to a stimulus when rare than when common, a phenomenon termed stimulus-specific adaptation (SSA). Here we compare stimulus-specific adaptation with scalp-recorded deviance-related responses. We conclude that early markers of deviance detection in the time range of the MLR could be a direct correlate of cortical SSA. Both occur at an early level of cortical activation, both are robust findings with low-probability stimuli, and both show properties of genuine deviance detection. Their causal relation with the later scalp-recorded MMN is a key question in this field.

  15. An early modern human from Tianyuan Cave, Zhoukoudian, China

    PubMed Central

    Shang, Hong; Tong, Haowen; Zhang, Shuangquan; Chen, Fuyou; Trinkaus, Erik

    2007-01-01

    Thirty-four elements of an early modern human (EMH) were found in Tianyuan Cave, Zhoukoudian, China in 2003. Dated to 42,000–39,000 calendrical years before present by using direct accelerator mass spectrometry radiocarbon, the Tianyuan 1 skeleton is among the oldest directly dated EMHs in eastern Eurasia. Morphological comparison shows Tianyuan 1 to have a series of derived modern human characteristics, including a projecting tuber symphyseos, a high anterior symphyseal angle, a broad scapular glenoid fossa, a reduced hamulus, a gluteal buttress, and a pilaster on the femora. Other features of Tianyuan 1 that are more common among EMHs are its modest humeral pectoralis major tuberosities, anteriorly rotated radial tuberosity, reduced radial curvature, and modest talar trochlea. It also lacks several mandibular features common among western Eurasian late archaic humans, including mandibular foramen bridging, mandibular notch asymmetry, and a large superior medial pterygoid tubercle. However, Tianyuan 1 exhibits several late archaic human features, such as its anterior to posterior dental proportions, a large hamulus length, and a broad and rounded distal phalangeal tuberosity. This morphological pattern implies that a simple spread of modern humans from Africa is unlikely. PMID:17416672

  16. Water, plants, and early human habitats in eastern Africa

    PubMed Central

    Magill, Clayton R.; Ashley, Gail M.; Freeman, Katherine H.

    2013-01-01

    Water and its influence on plants likely exerted strong adaptive pressures in human evolution. Understanding relationships among water, plants, and early humans is limited both by incomplete terrestrial records of environmental change and by indirect proxy data for water availability. Here we present a continuous record of stable hydrogen-isotope compositions (expressed as δD values) for lipid biomarkers preserved in lake sediments from an early Pleistocene archaeological site in eastern Africa—Olduvai Gorge. We convert sedimentary leaf- and algal-lipid δD values into estimates for ancient source-water δD values by accounting for biochemical, physiological, and environmental influences on isotopic fractionation via published water–lipid enrichment factors for living plants, algae, and recent sediments. Reconstructed precipitation and lake-water δD values, respectively, are consistent with modern isotopic hydrology and reveal that dramatic fluctuations in water availability accompanied ecosystem changes. Drier conditions, indicated by less negative δD values, occur in association with stable carbon-isotopic evidence for open, C4-dominated grassland ecosystems. Wetter conditions, indicated by lower δD values, are associated with expanded woody cover across the ancient landscape. Estimates for ancient precipitation amounts, based on reconstructed precipitation δD values, range between approximately 250 and 700 mm·y−1 and are consistent with modern precipitation data for eastern Africa. We conclude that freshwater availability exerted a substantial influence on eastern African ecosystems and, by extension, was central to early human proliferation during periods of rapid climate change. PMID:23267102

  17. Water, plants, and early human habitats in eastern Africa.

    PubMed

    Magill, Clayton R; Ashley, Gail M; Freeman, Katherine H

    2013-01-22

    Water and its influence on plants likely exerted strong adaptive pressures in human evolution. Understanding relationships among water, plants, and early humans is limited both by incomplete terrestrial records of environmental change and by indirect proxy data for water availability. Here we present a continuous record of stable hydrogen-isotope compositions (expressed as δD values) for lipid biomarkers preserved in lake sediments from an early Pleistocene archaeological site in eastern Africa--Olduvai Gorge. We convert sedimentary leaf- and algal-lipid δD values into estimates for ancient source-water δD values by accounting for biochemical, physiological, and environmental influences on isotopic fractionation via published water-lipid enrichment factors for living plants, algae, and recent sediments. Reconstructed precipitation and lake-water δD values, respectively, are consistent with modern isotopic hydrology and reveal that dramatic fluctuations in water availability accompanied ecosystem changes. Drier conditions, indicated by less negative δD values, occur in association with stable carbon-isotopic evidence for open, C(4)-dominated grassland ecosystems. Wetter conditions, indicated by lower δD values, are associated with expanded woody cover across the ancient landscape. Estimates for ancient precipitation amounts, based on reconstructed precipitation δD values, range between approximately 250 and 700 mm · y(-1) and are consistent with modern precipitation data for eastern Africa. We conclude that freshwater availability exerted a substantial influence on eastern African ecosystems and, by extension, was central to early human proliferation during periods of rapid climate change.

  18. A unique chromatin signature uncovers early developmental enhancers in humans.

    PubMed

    Rada-Iglesias, Alvaro; Bajpai, Ruchi; Swigut, Tomek; Brugmann, Samantha A; Flynn, Ryan A; Wysocka, Joanna

    2011-02-10

    Cell-fate transitions involve the integration of genomic information encoded by regulatory elements, such as enhancers, with the cellular environment. However, identification of genomic sequences that control human embryonic development represents a formidable challenge. Here we show that in human embryonic stem cells (hESCs), unique chromatin signatures identify two distinct classes of genomic elements, both of which are marked by the presence of chromatin regulators p300 and BRG1, monomethylation of histone H3 at lysine 4 (H3K4me1), and low nucleosomal density. In addition, elements of the first class are distinguished by the acetylation of histone H3 at lysine 27 (H3K27ac), overlap with previously characterized hESC enhancers, and are located proximally to genes expressed in hESCs and the epiblast. In contrast, elements of the second class, which we term 'poised enhancers', are distinguished by the absence of H3K27ac, enrichment of histone H3 lysine 27 trimethylation (H3K27me3), and are linked to genes inactive in hESCs and instead are involved in orchestrating early steps in embryogenesis, such as gastrulation, mesoderm formation and neurulation. Consistent with the poised identity, during differentiation of hESCs to neuroepithelium, a neuroectoderm-specific subset of poised enhancers acquires a chromatin signature associated with active enhancers. When assayed in zebrafish embryos, poised enhancers are able to direct cell-type and stage-specific expression characteristic of their proximal developmental gene, even in the absence of sequence conservation in the fish genome. Our data demonstrate that early developmental enhancers are epigenetically pre-marked in hESCs and indicate an unappreciated role of H3K27me3 at distal regulatory elements. Moreover, the wealth of new regulatory sequences identified here provides an invaluable resource for studies and isolation of transient, rare cell populations representing early stages of human embryogenesis.

  19. Phylogenomic reconstruction indicates mitochondrial ancestor was an energy parasite.

    PubMed

    Wang, Zhang; Wu, Martin

    2014-01-01

    Reconstruction of mitochondrial ancestor has great impact on our understanding of the origin of mitochondria. Previous studies have largely focused on reconstructing the last common ancestor of all contemporary mitochondria (proto-mitochondria), but not on the more informative pre-mitochondria (the last common ancestor of mitochondria and their alphaproteobacterial sister clade). Using a phylogenomic approach and leveraging on the increased taxonomic sampling of alphaproteobacterial and eukaryotic genomes, we reconstructed the metabolisms of both proto-mitochondria and pre-mitochondria. Our reconstruction depicts a more streamlined proto-mitochondrion than these predicted by previous studies, and revealed several novel insights into the mitochondria-derived eukaryotic metabolisms including the lipid metabolism. Most strikingly, pre-mitochondrion was predicted to possess a plastid/parasite type of ATP/ADP translocase that imports ATP from the host, which posits pre-mitochondrion as an energy parasite that directly contrasts with the current role of mitochondria as the cell's energy producer. In addition, pre-mitochondrion was predicted to encode a large number of flagellar genes and several cytochrome oxidases functioning under low oxygen level, strongly supporting the previous finding that the mitochondrial ancestor was likely motile and capable of oxidative phosphorylation under microoxic condition.

  20. The great divides: Ardipithecus ramidus reveals the postcrania of our last common ancestors with African apes.

    PubMed

    Lovejoy, C Owen; Suwa, Gen; Simpson, Scott W; Matternes, Jay H; White, Tim D

    2009-10-01

    Genomic comparisons have established the chimpanzee and bonobo as our closest living relatives. However, the intricacies of gene regulation and expression caution against the use of these extant apes in deducing the anatomical structure of the last common ancestor that we shared with them. Evidence for this structure must therefore be sought from the fossil record. Until now, that record has provided few relevant data because available fossils were too recent or too incomplete. Evidence from Ardipithecus ramidus now suggests that the last common ancestor lacked the hand, foot, pelvic, vertebral, and limb structures and proportions specialized for suspension, vertical climbing, and knuckle-walking among extant African apes. If this hypothesis is correct, each extant African ape genus must have independently acquired these specializations from more generalized ancestors who still practiced careful arboreal climbing and bridging. African apes and hominids acquired advanced orthogrady in parallel. Hominoid spinal invagination is an embryogenetic mechanism that reoriented the shoulder girdle more laterally. It was unaccompanied by substantial lumbar spine abbreviation, an adaptation restricted to vertical climbing and/or suspension. The specialized locomotor anatomies and behaviors of chimpanzees and gorillas therefore constitute poor models for the origin and evolution of human bipedality.

  1. On the tool use behavior of the bonobo-chimpanzee last common ancestor, and the origins of hominine stone tool use.

    PubMed

    Haslam, Michael

    2014-10-01

    The last common ancestor (LCA) shared by chimpanzees (Pan troglodytes) and bonobos (P. paniscus) was an Early Pleistocene African ape, which, based on the behavior of modern chimpanzees, may be assumed to be a tool-using animal. However, the character of tool use in the Pan lineage prior to the 20th century is largely unknown. Here, I use available data on wild bonobo tool use and emerging molecular estimates of demography during Pan evolution to hypothesise the plausible tool use behavior of the bonobo-chimpanzee LCA (or "Pancestor") at the start of the Pleistocene, over 2 million years ago. This method indicates that the common ancestor of living Pan apes likely used plant tools for probing, sponging, and display, but it did not use stone tools. Instead, stone tool use appears to have been independently invented by Western African chimpanzees (P. t. verus) during the Middle Pleistocene in the region of modern Liberia-Ivory Coast-Guinea, possibly as recently as 200,000-150,000 years ago. If this is the case, then the LCA of humans and chimpanzees likely also did not use stone tools, and this trait probably first emerged among hominins in Pliocene East Africa. This review also suggests that the consistently higher population sizes of Central African chimpanzees (P. t. troglodytes) over the past million years may have contributed to the increased complexity of wild tool use seen in this sub-species today.

  2. Facilitated early cortical processing of nude human bodies.

    PubMed

    Alho, Jussi; Salminen, Nelli; Sams, Mikko; Hietanen, Jari K; Nummenmaa, Lauri

    2015-07-01

    Functional brain imaging has identified specialized neural systems supporting human body perception. Responses to nude vs. clothed bodies within this system are amplified. However, it remains unresolved whether nude and clothed bodies are processed by same cerebral networks or whether processing of nude bodies recruits additional affective and arousal processing areas. We recorded simultaneous MEG and EEG while participants viewed photographs of clothed and nude bodies. Global field power revealed a peak ∼145ms after stimulus onset to both clothed and nude bodies, and ∼205ms exclusively to nude bodies. Nude-body-sensitive responses were centered first (100-200ms) in the extrastriate and fusiform body areas, and subsequently (200-300ms) in affective-motivational areas including insula and anterior cingulate cortex. We conclude that visibility of sexual features facilitates early cortical processing of human bodies, the purpose of which is presumably to trigger sexual behavior and ultimately ensure reproduction.

  3. Late Pleistocene climate drivers of early human migration

    NASA Astrophysics Data System (ADS)

    Timmermann, Axel; Friedrich, Tobias

    2016-10-01

    On the basis of fossil and archaeological data it has been hypothesized that the exodus of Homo sapiens out of Africa and into Eurasia between ~50–120 thousand years ago occurred in several orbitally paced migration episodes. Crossing vegetated pluvial corridors from northeastern Africa into the Arabian Peninsula and the Levant and expanding further into Eurasia, Australia and the Americas, early H. sapiens experienced massive time-varying climate and sea level conditions on a variety of timescales. Hitherto it has remained difficult to quantify the effect of glacial- and millennial-scale climate variability on early human dispersal and evolution. Here we present results from a numerical human dispersal model, which is forced by spatiotemporal estimates of climate and sea level changes over the past 125 thousand years. The model simulates the overall dispersal of H. sapiens in close agreement with archaeological and fossil data and features prominent glacial migration waves across the Arabian Peninsula and the Levant region around 106–94, 89–73, 59–47 and 45–29 thousand years ago. The findings document that orbital-scale global climate swings played a key role in shaping Late Pleistocene global population distributions, whereas millennial-scale abrupt climate changes, associated with Dansgaard–Oeschger events, had a more limited regional effect.

  4. Microcalcifications in Early Intimal Lesions of Atherosclerotic Human Coronary Arteries

    PubMed Central

    Roijers, Ruben B.; Debernardi, Nicola; Cleutjens, Jack P.M.; Schurgers, Leon J.; Mutsaers, Peter H.A.; van der Vusse, Ger J.

    2011-01-01

    Although calcium (Ca) precipitation may play a pathogenic role in atherosclerosis, information on temporal patterns of microcalcifications in human coronary arteries, their relation to expression of calcification-regulating proteins, and colocalization with iron (Fe) and zinc (Zn) is scarce. Human coronary arteries were analyzed post mortem with a proton microprobe for element concentrations and stained (immuno)histochemically for morphological and calcification-regulating proteins. Microcalcifications were occasionally observed in preatheroma type I atherosclerotic intimal lesions. Their abundance increased in type II, III, and IV lesions. Moreover, their appearance preceded increased expression of calcification-regulating proteins, such as osteocalcin and bone morphogenetic protein-2. In contrast, their presence coincided with increased expression of uncarboxylated matrix Gla protein (MGP), whereas the content of carboxylated MGP was increased in type III and IV lesions, indicating delayed posttranslational conversion of biologically inactive into active MGP. Ca/phosphorus ratios of the microcalcifications varied from 1.6 to 3.0, including amorphous Ca phosphates. Approximately 75% of microcalcifications colocalized with the accumulation of Fe and Zn. We conclude that Ca microprecipitation occurs in the early stages of atherosclerosis, inferring a pathogenic role in the sequel of events, resulting in overt atherosclerotic lesions. Microcalcifications may be caused by local events triggering the precipitation of Ca rather than by increased expression of calcification-regulating proteins. The high degree of colocalization with Fe and Zn suggests a mutual relationship between these trace elements and early deposition of Ca salts. PMID:21531376

  5. Early Human Evolution in the Western Palaearctic: Ecological Scenarios

    NASA Astrophysics Data System (ADS)

    Carrión, José S.; Rose, James; Stringer, Chris

    2011-06-01

    This review presents the themes of a special issue dealing with environmental scenarios of human evolution during the Early Pleistocene (2.6-0.78 Ma; MIS 103-MIS 19) and early Middle Pleistocene (0.78-0.47 Ma; MIS 19-base of MIS 12) within the western Palaearctic. This period is one of dramatic changes in the climates and the distribution of Palaearctic biota. These changes have played their role in generating adaptive and phyletic patterns within the human ancestry, involving several species such as Homo habilis, "Homo georgicus", Homo erectus, Homo antecessor and Homo heidelbergensis. In the archaeological record, these species include the Oldowan (Mode 1) and Acheulian (Mode 2) lithic technologies. Taphonomic considerations of palaeoecological research in hominin-bearing sites are provided and evaluated. Syntheses are provided for north Africa, western Asia, the Mediterranean Basin, Britain, and continental Europe. Palaeoenvironmental reconstructions based on multidisciplinary data are given for Ain Boucherit, Ain Hanech and El-Kherba in Algeria, Dmanisi in Georgia, Atapuerca, Cueva Negra, and the Orce Basin in Spain, Monte Poggiolo and Pirro Nord in Italy, Pont-de-Lavaud in France, and Mauer in Germany. The state of the art with the Out of Africa 1 dispersal model is reviewed. A source-sink dynamics model for Palaeolithic Europe is described to explain the morphological disparity of H. heidelbergensis (we will sometimes use the informal name "Heidelbergs") and early Neanderthals. Other aspects debated here are the selective value of habitat mosaics including reconstructions based on mammal and avian databases, and the role of geological instability combined with topographic complexity. This review is completed by addressing the question of whether the appearance of evolutionary trends within hominins is concentrated in regions of highest worldwide biological diversity (biodiversity hotspots). It is concluded that the keys for the activation of evolutionary

  6. Carbon cycle and climate commitments from early human interference

    NASA Astrophysics Data System (ADS)

    Zickfeld, K.; Solomon, S.

    2015-12-01

    According to the early anthropogenic hypothesis proposed by Ruddiman (2003), human influence on Earth's climate began several thousand years before the beginning of the industrial era. Agriculture and deforestation starting around 8000 years before present (BP) and slowly increasing over the Holocene, would have led to an increase in atmospheric methane (CH4) and carbon dioxide (CO2) concentration, preventing a natural cooling of Earth's climate. Here, the emphasis is not on testing Ruddiman's hypothesis, but rather on exploring the carbon cycle and climate commitment from potential early CH4 and CO2 emissions. In contrast to modern greenhouse gas emissions, early emissions occurred over millennia, allowing the climate system to come to near-equilibrium with the applied forcing. We perform two transient Holocene simulations with an Earth system model of intermediate complexity - the University of Victoria Earth System Climate Model (UVic ESCM). The first simulation is a standard transient Holocene simulation, forced with reconstructed changes in CO2 and CH4 concentrations and orbital and volcanic forcing. The second simulation is forced with CO2 and CH4 concentrations corrected for the net anthropogenic contribution postulated by Ruddiman (2007), with other forcings evolving as in the standard simulation. The difference in diagnosed emissions between the two simulations allows us to determine the anthropogenic emissions. After year 1850, anthropogenic CO2 and CH4 emissions are set to zero and the simulations continued for several hundred years. In this paper, we analyze the carbon cycle and climate response to the applied forcings, and quantify the resulting (post 1850) commitment from early anthropogenic interference.

  7. Deciding Termination for Ancestor Match- Bounded String Rewriting Systems

    NASA Technical Reports Server (NTRS)

    Geser, Alfons; Hofbauer, Dieter; Waldmann, Johannes

    2005-01-01

    Termination of a string rewriting system can be characterized by termination on suitable recursively defined languages. This kind of termination criteria has been criticized for its lack of automation. In an earlier paper we have shown how to construct an automated termination criterion if the recursion is aligned with the rewrite relation. We have demonstrated the technique with Dershowitz's forward closure criterion. In this paper we show that a different approach is suitable when the recursion is aligned with the inverse of the rewrite relation. We apply this idea to Kurth's ancestor graphs and obtain ancestor match-bounded string rewriting systems. Termination is shown to be decidable for this class. The resulting method improves upon those based on match-boundedness or inverse match-boundedness.

  8. A primitive fish close to the common ancestor of tetrapods and lungfish.

    PubMed

    Zhu, Min; Yu, Xiaobo

    2002-08-15

    The relationship of the three living groups of sarcopterygians or lobe-finned fish (tetrapods, lungfish and coelacanths) has been a matter of debate. Although opinions still differ, most recent phylogenies suggest that tetrapods are more closely related to lungfish than to coelacanths. However, no previously known fossil taxon exhibits a concrete character combination approximating the condition expected in the last common ancestor of tetrapods and lungfish -- and it is still poorly understood how early sarcopterygians diverged into the tetrapod lineage (Tetrapodomorpha) and the lungfish lineage (Dipnomorpha). Here we describe a fossil sarcopterygian fish, Styloichthys changae gen. et sp. nov., that possesses an eyestalk and which exhibits the character combination expected in a stem group close to the last common ancestor of tetrapods and lungfish. Styloichthys from the Lower Devonian of China bridges the morphological gap between stem-group sarcopterygians (Psarolepis and Achoania) and basal tetrapodomorphs/basal dipnomorphs. It provides information that will help in the study of the relationship of early sarcopterygians, and which will also help to resolve the tetrapod-lungfish divergence into a documented sequence of character acquisition.

  9. Early lunar resource utilization - A key to human exploration

    NASA Astrophysics Data System (ADS)

    Joosten, B. K.; Guerra, Lisa A.

    1993-09-01

    Lunar exploration attempts have suffered from high projected costs of spaceflight hardware development and production. A method of reducing these costs is proposed: the utilization of propellant produced on the moon at program inception. This technique permits down-sizing of the required transportation systems and should enable lunar missions using a single STS-derived launch vehicle. The technical feasibility of this concept has been validated by preliminary space transportation and surface system design efforts. The required technologies emphasize electric surface vehicles, automation and robotics, and reliable chemical processing. Cost assessments were performed and compared to estimates based on a lunar exploration scheme to evaluate the effectiveness of this strategy. Results indicate that early production and utilization of lunar propellant leads to lower hardware development costs, lower cost uncertainties, and a reduction in human transportation costs of approximately fifty percent.

  10. Metabolic gene profile in early human fetal heart development.

    PubMed

    Iruretagoyena, J I; Davis, W; Bird, C; Olsen, J; Radue, R; Teo Broman, A; Kendziorski, C; Splinter BonDurant, S; Golos, T; Bird, I; Shah, D

    2014-07-01

    The primitive cardiac tube starts beating 6-8 weeks post fertilization in the developing embryo. In order to describe normal cardiac development during late first and early second trimester in human fetuses this study used microarray and pathways analysis and created a corresponding 'normal' database. Fourteen fetal hearts from human fetuses between 10 and 18 weeks of gestational age (GA) were prospectively collected at the time of elective termination of pregnancy. RNA from recovered tissues was used for transcriptome analysis with Affymetrix 1.0 ST microarray chip. From the amassed data we investigated differences in cardiac development within the 10-18 GA period dividing the sample by GA in three groups: 10-12 (H1), 13-15 (H2) and 16-18 (H3) weeks. A fold change of 2 or above adjusted for a false discovery rate of 5% was used as initial cutoff to determine differential gene expression for individual genes. Test for enrichment to identify functional groups was carried out using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Array analysis correctly identified the cardiac specific genes, and transcripts reported to be differentially expressed were confirmed by qRT-PCR. Single transcript and Ontology analysis showed first trimester heart expression of myosin-related genes to be up-regulated >5-fold compared with second trimester heart. In contrast the second trimester hearts showed further gestation-related increases in many genes involved in energy production and cardiac remodeling. In conclusion, fetal heart development during the first trimester was dominated by heart-specific genes coding for myocardial development and differentiation. During the second trimester, transcripts related to energy generation and cardiomyocyte communication for contractile coordination/proliferation were more dominant. Transcripts related to fatty acid metabolism can be seen as early as 10 weeks and clearly increase as the heart matures. Retinol

  11. Early maturation of the linguistic dorsal pathway in human infants.

    PubMed

    Leroy, François; Glasel, Hervé; Dubois, Jessica; Hertz-Pannier, Lucie; Thirion, Bertrand; Mangin, Jean-François; Dehaene-Lambertz, Ghislaine

    2011-01-26

    Human infants, unlike even closely related primates, exhibit a remarkable capacity for language learning. Yet how the underlying anatomical network matures remains largely unknown. The classical view is that of a largely immature brain comprising only a few islands of maturity in primary cortices. This view has favored a description of learning based on bottom-up algorithms and has tended to discard the role of frontal regions, which were assumed to be barely functional early on. Here, using an index based on the normalized T2-weighted magnetic resonance signal, we have quantified maturation within the linguistic network in fourteen 1- to 4-month-old infants. Our results show first that the ventral superior temporal sulcus (STS), and not the inferior frontal area, is the less mature perisylvian region. A significant difference of maturation in the STS favoring the right side is an early testimony of the distinctive left-right development of this structure observed during the whole life. Second, asymmetries of maturation in Broca's area were correlated with asymmetries in the posterior STS and in the parietal segment of the arcuate fasciculus, suggesting that an efficient frontotemporal dorsal pathway might provide infants with a phonological loop circuitry much earlier than expected. PMID:21273434

  12. mRNAs from human adenovirus 2 early region 4.

    PubMed Central

    Virtanen, A; Gilardi, P; Näslund, A; LeMoullec, J M; Pettersson, U; Perricaudet, M

    1984-01-01

    The molecular structure of the mRNAs from early region 4 of human adenovirus 2 has been studied by Northern blot analysis, S1 nuclease analysis, and sequence analysis of cDNA clones. The results make it possible to identify four different splice donor sites and six different splice acceptor sites. The structure of 12 different mRNAs can be deduced from the analysis. The mRNAs have identical 5' and 3' ends and are thus likely to be processed from a common mRNA precursor by differential splicing. The different mRNA species are formed by the removal of one to three introns, and they all carry a short 5' leader segment. The introns appear to serve two functions; they either place a 5' leader segment in juxtaposition with an open reading frame or fuse two open translational reading frames. The early region 4 mRNAs can encode at least seven unique polypeptides. Images PMID:6088804

  13. Early Trypanosoma cruzi Infection Reprograms Human Epithelial Cells

    PubMed Central

    Chiribao, María Laura; Libisch, Gabriela; Parodi-Talice, Adriana; Robello, Carlos

    2014-01-01

    Trypanosoma cruzi, the causative agent of Chagas disease, has the peculiarity, when compared with other intracellular parasites, that it is able to invade almost any type of cell. This property makes Chagas a complex parasitic disease in terms of prophylaxis and therapeutics. The identification of key host cellular factors that play a role in the T. cruzi invasion is important for the understanding of disease pathogenesis. In Chagas disease, most of the focus is on the response of macrophages and cardiomyocytes, since they are responsible for host defenses and cardiac lesions, respectively. In the present work, we studied the early response to infection of T. cruzi in human epithelial cells, which constitute the first barrier for establishment of infection. These studies identified up to 1700 significantly altered genes regulated by the immediate infection. The global analysis indicates that cells are literally reprogrammed by T. cruzi, which affects cellular stress responses (neutrophil chemotaxis, DNA damage response), a great number of transcription factors (including the majority of NFκB family members), and host metabolism (cholesterol, fatty acids, and phospholipids). These results raise the possibility that early host cell reprogramming is exploited by the parasite to establish the initial infection and posterior systemic dissemination. PMID:24812617

  14. Early immune responses accompanying human asymptomatic Ebola infections

    PubMed Central

    Leroy, E M; Baize, S; Debre, P; Lansoud-Soukate, J; Mavoungou, E

    2001-01-01

    In a recent study we identified certain asymptomatic individuals infected by Ebola virus (EBOV) who mounted specific IgG and early and strong inflammatory responses. Here, we further characterized the primary immune response to EBOV during the course of asymptomatic infection in humans. Inflammatory responses occurred in temporal association with anti-inflammatory phase composed by soluble antagonist IL-1RA, circulating TNF receptors, IL-10 and cortisol. At the end of the inflammatory process, mRNA expression of T-cell cytokines (IL-2 and IL-4) and activation markers (CD28, CD40L and CTLA4) was up-regulated, strongly suggesting T-cell activation. This T-cell activation was followed by EBOV-specific IgG responses (mainly IgG3 ang IgG1), and by marked and sustained up-regulation of IFNγ, FasL and perforin mRNA expression, suggesting activation of cytotoxic cells. The terminal down-regulation of these latter markers coincided with the release of the apoptotic marker 41/7 NMP in blood and with the disappearance of viral RNA from PBMC, suggesting that infected cells are eliminated by cytotoxic mechanisms. Finally, RT-PCR analysis of TCR-Vβ repertoire usage showed that TCR-Vβ12 mRNA was never expressed during the infection. Taken together, these findings improve our understanding about immune response during human asymptomatic Ebola infection, and throw new light on protection against Ebola virus. PMID:11472407

  15. Degradation phase of apoptosis during the early stages of human metanephros development.

    PubMed

    Wagner, Filip; Erdösová, Bela; Kylarová, Dana

    2004-12-01

    Apoptosis as a vital process is necessary for human intrauterine development. Not only the induction and course of apoptosis, but engulfment of the apoptotic cells (bodies) were the centre of our interest. Macrophages were detected in the early stages of human intrauterine development and the role of macrophages in the clearance of apoptotic cells in the early stages of human metanephros development was confirmed.

  16. Buds from the tree of life: linking compartmentalized prokaryotes and eukaryotes by a non-hyperthermophile common ancestor and implications for understanding Archaean microbial communities

    NASA Astrophysics Data System (ADS)

    Fuerst, John A.; Nisbet, Euan G.

    2004-07-01

    The origin of the first nucleated eukaryote and the nature of the last common ancestor of the three domains of life are major questions in the evolutionary biology of cellular life on Earth, the solutions to which may be linked. Planctomycetes are unusual compartmentalized bacteria that include a membrane-bounded nucleoid. The possibility that they constitute a very deep branch of the domain Bacteria suggests a model for the evolution of the three domains of life from a last common ancestor that was a mesophile or moderate thermophile with a compartmentalized eukaryote-like cell plan. Planctomycetes and some members of the domain Archaea may have retained cell compartmentalization present in an original eukaryote-like last common ancestor of the three domains of life. The implications of this model for possible habitats of the early evolution of domains of cellular life and for interpretation of geological evidence relating to those habitats and the early emergence of life are examined here.

  17. Life cycle evolution: was the eumetazoan ancestor a holopelagic, planktotrophic gastraea?

    PubMed Central

    2013-01-01

    Background Two theories for the origin of animal life cycles with planktotrophic larvae are now discussed seriously: The terminal addition theory proposes a holopelagic, planktotrophic gastraea as the ancestor of the eumetazoans with addition of benthic adult stages and retention of the planktotrophic stages as larvae, i.e. the ancestral life cycles were indirect. The intercalation theory now proposes a benthic, deposit-feeding gastraea as the bilaterian ancestor with a direct development, and with planktotrophic larvae evolving independently in numerous lineages through specializations of juveniles. Results Information from the fossil record, from mapping of developmental types onto known phylogenies, from occurrence of apical organs, and from genetics gives no direct information about the ancestral eumetazoan life cycle; however, there are plenty of examples of evolution from an indirect development to direct development, and no unequivocal example of evolution in the opposite direction. Analyses of scenarios for the two types of evolution are highly informative. The evolution of the indirect spiralian life cycle with a trochophora larva from a planktotrophic gastraea is explained by the trochophora theory as a continuous series of ancestors, where each evolutionary step had an adaptational advantage. The loss of ciliated larvae in the ecdysozoans is associated with the loss of outer ciliated epithelia. A scenario for the intercalation theory shows the origin of the planktotrophic larvae of the spiralians through a series of specializations of the general ciliation of the juvenile. The early steps associated with the enhancement of swimming seem probable, but the following steps which should lead to the complicated downstream-collecting ciliary system are without any advantage, or even seem disadvantageous, until the whole structure is functional. None of the theories account for the origin of the ancestral deuterostome (ambulacrarian) life cycle. Conclusions All

  18. Phylogenetic reconstruction of parental-care systems in the ancestors of birds.

    PubMed Central

    Tullberg, Birgitta S; Ah-King, Malin; Temrin, Hans

    2002-01-01

    Due to the controversy surrounding incipient avian parental care, ancestral parental care systems were reconstructed in a phylogeny including major extant amniote lineages. Using two different resolutions for the basal avian branches, transitions between the states no care, female care, biparental care and male care were inferred for the most basal branches of the tree. Uniparental female care was inferred for the lineage to birds and crocodiles. Using a phylogeny where ratites and tinamous branch off early and an ordered character-state assumption, a transition to biparental care was inferred for the ancestor of birds. This ancestor could be any organism along the lineage leading from the crocodile-bird split up to modern birds, not necessarily the original bird. We discuss the support for alternative avian phylogenies and the homology in parental care between crocodiles and birds. We suggest that the phylogenetic pattern should be used as a starting point for a more detailed analysis of parental care systems in birds and their relatives. PMID:11958694

  19. Resting state functional connectivity in early blind humans

    PubMed Central

    Burton, Harold; Snyder, Abraham Z.; Raichle, Marcus E.

    2014-01-01

    Task-based neuroimaging studies in early blind humans (EB) have demonstrated heightened visual cortex responses to non-visual paradigms. Several prior functional connectivity studies in EB have shown altered connections consistent with these task-based results. But these studies generally did not consider behavioral adaptations to lifelong blindness typically observed in EB. Enhanced cognitive abilities shown in EB include greater serial recall and attention to memory. Here, we address the question of the extent to which brain intrinsic activity in EB reflects such adaptations. We performed a resting-state functional magnetic resonance imaging study contrasting 14 EB with 14 age/gender matched normally sighted controls (NS). A principal finding was markedly greater functional connectivity in EB between visual cortex and regions typically associated with memory and cognitive control of attention. In contrast, correlations between visual cortex and non-deprived sensory cortices were significantly lower in EB. Thus, the available data, including that obtained in prior task-based and resting state fMRI studies, as well as the present results, indicate that visual cortex in EB becomes more heavily incorporated into functional systems instantiating episodic recall and attention to non-visual events. Moreover, EB appear to show a reduction in interactions between visual and non-deprived sensory cortices, possibly reflecting suppression of inter-sensory distracting activity. PMID:24778608

  20. Archaeal ancestors of eukaryotes: not so elusive any more.

    PubMed

    Koonin, Eugene V

    2015-01-01

    The origin of eukaryotes is one of the hardest problems in evolutionary biology and sometimes raises the ominous specter of irreducible complexity. Reconstruction of the gene repertoire of the last eukaryotic common ancestor (LECA) has revealed a highly complex organism with a variety of advanced features but no detectable evolutionary intermediates to explain their origin. Recently, however, genome analysis of diverse archaea led to the discovery of apparent ancestral versions of several signature eukaryotic systems, such as the actin cytoskeleton and the ubiquitin network, that are scattered among archaea. These findings inspired the hypothesis that the archaeal ancestor of eukaryotes was an unusually complex form with an elaborate intracellular organization. The latest striking discovery made by deep metagenomic sequencing vindicates this hypothesis by showing that in phylogenetic trees eukaryotes fall within a newly identified archaeal group, the Lokiarchaeota, which combine several eukaryotic signatures previously identified in different archaea. The discovery of complex archaea that are the closest living relatives of eukaryotes is most compatible with the symbiogenetic scenario for eukaryogenesis.

  1. Hybrid origin of the Pliocene ancestor of wild goats.

    PubMed

    Ropiquet, Anne; Hassanin, Alexandre

    2006-11-01

    Recent theories on speciation suggest that interspecific hybridization is an important mechanism for explaining adaptive radiation. According to this view, hybridization can promote the rapid transfer of adaptations between different species; the hybrid population thus invades new habitats and diversifies into a variety of new species. Although hybridization is well accepted as a fairly common mechanism for diversification in plants, its role in the evolution of animals is more controversial, because reduced fitness would typically condemn animal hybrids to an evolutionary dead-end. Here, we examine DNA sequences of four mitochondrial and four nuclear genes selected for resolving phylogenetic relationships between goats, sheep, and their allies. Our analyses provide evidence of strong discordance for the position of Capra between mitochondrial and nuclear phylogenies. We suggest that the common ancestor of wild goats arose from interspecific hybridization, and that the mitochondrial genome of a species better adapted to life at high altitudes was transferred via this route into the common ancestor of Capra. We propose that the acquisition of more efficient mitochondria has conferred a selective advantage on goats, allowing their rapid adaptive radiation during the Plio-Pleistocene epoch. Our study therefore agrees with theories that predict an important role for interspecific hybridization in the evolution and diversification of animal species. PMID:16837213

  2. Early Human Occupation on the Northeast Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Rhode, D.; Madsen, D.; Brantingham, P.; Perrault, C.

    2010-12-01

    The Tibetan Plateau presents great challenges for human occupation: low oxygen, high ultraviolet radiation, harsh seasonal climate, low overall biological productivity. How and when early humans were able to cope physiologically, genetically, and behaviorally with these extremes is important for understanding the history of human adaptive flexibility. Our investigations of prehistoric human settlement on the northeast Tibetan Plateau focus on (a) establishing well-dated evidence for occupation of altitudes >3000 m, (b) the environmental context of high altitude adaptation, and (c) relations of hunting and pastoralism to lower-altitude agrarian systems. We observe two major prehistoric settlement patterns in the Qinghai Lake area. The earliest, ~15,000-7500 yr old, consists of small isolated firehearths with sparse associated stone tools and wild mammal remains (1). Numerous hearths often occur in the same localities, indicating repeated short-duration occupations by small hunting parties. A second pattern, ~9000-4000 yr old, was established during the Holocene climatic optimum. These sites represent prolonged seasonal residential occupation, containing dark anthropogenic midden, hearth and pit constructions, abundant stone tools, occasional ceramics, and abundant diverse faunal remains (including medium-large mammals but lacking domestic sheep/yak)(2). These Plateau-margin base camps allowed greater intensity of use of the high Plateau. Residential occupation was strongly influenced by nearby lower-altitude farming communities; development of the socioeconomic landscape along the Yellow River likely played at least as great a role in Plateau occupation patterns as did Holocene environmental changes. Holocene vegetation changes in the NE Tibetan Plateau have been attributed to climate (3) or anthropogenic modification (4). Our results document changes in shrub/tree presence from ~12,000-4000 BP, similar to pollen records, that likely reflect climate rather than

  3. Origin and Evolution of Water Oxidation before the Last Common Ancestor of the Cyanobacteria.

    PubMed

    Cardona, Tanai; Murray, James W; Rutherford, A William

    2015-05-01

    Photosystem II, the water oxidizing enzyme, altered the course of evolution by filling the atmosphere with oxygen. Here, we reconstruct the origin and evolution of water oxidation at an unprecedented level of detail by studying the phylogeny of all D1 subunits, the main protein coordinating the water oxidizing cluster (Mn4CaO5) of Photosystem II. We show that D1 exists in several forms making well-defined clades, some of which could have evolved before the origin of water oxidation and presenting many atypical characteristics. The most ancient form is found in the genome of Gloeobacter kilaueensis JS-1 and this has a C-terminus with a higher sequence identity to D2 than to any other D1. Two other groups of early evolving D1 correspond to those expressed under prolonged far-red illumination and in darkness. These atypical D1 forms are characterized by a dramatically different Mn4CaO5 binding site and a Photosystem II containing such a site may assemble an unconventional metal cluster. The first D1 forms with a full set of ligands to the Mn4CaO5 cluster are grouped with D1 proteins expressed only under low oxygen concentrations and the latest evolving form is the dominant type of D1 found in all cyanobacteria and plastids. In addition, we show that the plastid ancestor had a D1 more similar to those in early branching Synechococcus. We suggest each one of these forms of D1 originated from transitional forms at different stages toward the innovation and optimization of water oxidation before the last common ancestor of all known cyanobacteria.

  4. A rock-inhabiting ancestor for mutualistic and pathogen-rich fungal lineages

    PubMed Central

    Gueidan, C.; Villaseñor, C. R.; de Hoog, G. S.; Gorbushina, A. A.; Untereiner, W. A.; Lutzoni, F.

    2008-01-01

    Rock surfaces are unique terrestrial habitats in which rapid changes in the intensity of radiation, temperature, water supply and nutrient availability challenge the survival of microbes. A specialised, but diverse group of free-living, melanised fungi are amongst the persistent settlers of bare rocks. Multigene phylogenetic analyses were used to study relationships of ascomycetes from a variety of substrates, with a dataset including a broad sampling of rock dwellers from different geographical locations. Rock-inhabiting fungi appear particularly diverse in the early diverging lineages of the orders Chaetothyriales and Verrucariales. Although these orders share a most recent common ancestor, their lifestyles are strikingly different. Verrucariales are mostly lichen-forming fungi, while Chaetothyriales, by contrast, are best known as opportunistic pathogens of vertebrates (e.g. Cladophialophora bantiana and Exophiala dermatitidis, both agents of fatal brain infections) and saprophytes. The rock-dwelling habit is shown here to be key to the evolution of these two ecologically disparate orders. The most recent common ancestor of Verrucariales and Chaetothyriales is reconstructed as a non-lichenised rock-inhabitant. Ancestral state reconstructions suggest Verrucariales as one of the independent ascomycetes group where lichenisation has evolved on a hostile rock surface that might have favored this shift to a symbiotic lifestyle. Rock-inhabiting fungi are also ancestral to opportunistic pathogens, as they are found in the early diverging lineages of Chaetothyriales. In Chaetothyriales and Verrucariales, specific morphological and physiological traits (here referred to as extremotolerance) evolved in response to stresses in extreme conditions prevailing on rock surfaces. These factors facilitated colonisation of various substrates including the brains of vertebrates by opportunistic fungal pathogens, as well as helped establishment of a stable lichen symbiosis. PMID

  5. Origin and Evolution of Water Oxidation before the Last Common Ancestor of the Cyanobacteria

    PubMed Central

    Cardona, Tanai; Murray, James W.; Rutherford, A. William

    2015-01-01

    Photosystem II, the water oxidizing enzyme, altered the course of evolution by filling the atmosphere with oxygen. Here, we reconstruct the origin and evolution of water oxidation at an unprecedented level of detail by studying the phylogeny of all D1 subunits, the main protein coordinating the water oxidizing cluster (Mn4CaO5) of Photosystem II. We show that D1 exists in several forms making well-defined clades, some of which could have evolved before the origin of water oxidation and presenting many atypical characteristics. The most ancient form is found in the genome of Gloeobacter kilaueensis JS-1 and this has a C-terminus with a higher sequence identity to D2 than to any other D1. Two other groups of early evolving D1 correspond to those expressed under prolonged far-red illumination and in darkness. These atypical D1 forms are characterized by a dramatically different Mn4CaO5 binding site and a Photosystem II containing such a site may assemble an unconventional metal cluster. The first D1 forms with a full set of ligands to the Mn4CaO5 cluster are grouped with D1 proteins expressed only under low oxygen concentrations and the latest evolving form is the dominant type of D1 found in all cyanobacteria and plastids. In addition, we show that the plastid ancestor had a D1 more similar to those in early branching Synechococcus. We suggest each one of these forms of D1 originated from transitional forms at different stages toward the innovation and optimization of water oxidation before the last common ancestor of all known cyanobacteria. PMID:25657330

  6. Early Holocene human remains from the Argentinean Pampas: additional evidence for distinctive cranial morphology of early South Americans.

    PubMed

    Pucciarelli, Héctor M; Perez, S Ivan; Politis, Gustavo G

    2010-10-01

    The cranial morphology of Early Holocene American human samples is characterized by a long and narrow cranial vault, whereas more recent samples exhibit a shorter and wider cranial vault. Two hypotheses have been proposed to account for the morphological differences between early and late-American samples: (a) the migratory hypothesis that suggests that the morphological variation between early and late American samples was the result of a variable number of migratory waves; and (b) the local diversification hypothesis, that is, the morphological differences between early and late American samples were mainly generated by local, random (genetic drift), and nonrandom factors (selection and phenotypic plasticity). We present the first craniometric study of three early skulls from the Argentinean Pampas, dated ∼8,000 cal. years BP (Arroyo Seco 2, Chocorí, and La Tigra), and one associated with mega-faunal remains (Fontezuelas skull). In addition, we studied several Late Holocene samples. We show that the skulls from the Argentinean Pampas are morphologically similar to other Early Holocene American skulls (i.e., Lagoa Santa from Brazil, Tequendama, Checua, and Aguazuque from Colombia, Lauricocha from Peru, and early Mexicans) that exhibit long and narrow cranial vaults. These samples differ from the Late Holocene American samples that exhibit a shorter and wider cranial vault. Our results underscore the important differences in cranial morphology between early and late-American samples. However, we emphasize the need for further studies to discuss alternative hypotheses regarding such differences. PMID:20623674

  7. Palaeogenomics in cereals: modeling of ancestors for modern species improvement.

    PubMed

    Salse, Jérôme; Feuillet, Catherine

    2011-03-01

    During the last decade, technological improvements led to the development of large sets of plant genomic resources permitting the emergence of high-resolution comparative genomic studies. Synteny-based identification of seven shared duplications in cereals led to the modeling of a common ancestral genome structure of 33.6 Mb structured in five protochromosomes containing 9138 protogenes and provided new insights into the evolution of cereal genomes from their extinct ancestors. Recent palaeogenomic data indicate that whole genome duplications were a driving force in the evolutionary success of cereals over the last 50 to 70 millions years. Finally, detailed synteny and duplication relationships led to an improved representation of cereal genomes in concentric circles, thus providing a new reference tool for improved gene annotation and cross-genome markers development.

  8. Palaeogenomics of plants: synteny-based modelling of extinct ancestors.

    PubMed

    Abrouk, Michael; Murat, Florent; Pont, Caroline; Messing, Joachim; Jackson, Scott; Faraut, Thomas; Tannier, Eric; Plomion, Christophe; Cooke, Richard; Feuillet, Catherine; Salse, Jérôme

    2010-09-01

    In the past ten years, international initiatives have led to the development of large sets of genomic resources that allow comparative genomic studies between plant genomes at a high level of resolution. Comparison of map-based genomic sequences revealed shared intra-genomic duplications, providing new insights into the evolution of flowering plant genomes from common ancestors. Plant genomes can be presented as concentric circles, providing a new reference for plant chromosome evolutionary relationships and an efficient tool for gene annotation and cross-genome markers development. Recent palaeogenomic data demonstrate that whole-genome duplications have provided a motor for the evolutionary success of flowering plants over the last 50-70 million years.

  9. Will man wish to prevail? Some fundamental choices facing humanity early in the Third Millennium

    SciTech Connect

    Wood, L.L.

    1994-10-01

    With the subtle but occasionally vital exception of vaccination-induced immunity to many of the major infectious diseases, no human today is other than virtually identical biologically to those who greeted the dawn of the Second Millennium, nearly 1000 years ago. Culturally, however, we of the West are quite highly evolved from our ancestors of a millennium ago, primarily due to the advent of means for communicating with ever smaller latencies and ever higher bandwidths over ever greater distances in space and time: printed documents have been supplemented in succession by telephony, radio, video and, just now, the first personal communications sets. Also, within a fraction of a human lifetime from the present moment, the first prosthesis for the human brain has appeared and just very recently has become quite ubiquitous: digital computing systems. We are hardly members of the same species, culturally speaking; people of 1000 years ago would be truly and utterly lost in our communications-intensive civilization, and even a highly educated person from those times would swear that a personal computer equipped with a wireless communications module was as at least a familiar, if not a golem. Conversely, a computer-using person from our own times somehow translated back to 1000 A.D. would likely find the profound isolation and the ``informational slowness`` of life then to be acutely intolerable, certainly to a far greater extent than would a citizen of the High Middle Ages translated back to Augustus Caesar`s Rome.

  10. Investing in early human development: timing and economic efficiency.

    PubMed

    Doyle, Orla; Harmon, Colm P; Heckman, James J; Tremblay, Richard E

    2009-03-01

    Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the "antenatal investment hypothesis". We conclude by discussing a suite of new European interventions that will inform this optimal timing debate.

  11. Aberrant Time to Most Recent Common Ancestor as a Signature of Natural Selection.

    PubMed

    Hunter-Zinck, Haley; Clark, Andrew G

    2015-10-01

    Natural selection inference methods often target one mode of selection of a particular age and strength. However, detecting multiple modes simultaneously, or with atypical representations, would be advantageous for understanding a population's evolutionary history. We have developed an anomaly detection algorithm using distributions of pairwise time to most recent common ancestor (TMRCA) to simultaneously detect multiple modes of natural selection in whole-genome sequences. As natural selection distorts local genealogies in distinct ways, the method uses pairwise TMRCA distributions, which approximate genealogies at a nonrecombining locus, to detect distortions without targeting a specific mode of selection. We evaluate the performance of our method, TSel, for both positive and balancing selection over different time-scales and selection strengths and compare TSel's performance with that of other methods. We then apply TSel to the Complete Genomics diversity panel, a set of human whole-genome sequences, and recover loci previously inferred to be under positive or balancing selection.

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

    PubMed Central

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

    1999-01-01

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

  13. Inhibition of human placental progesterone and estrogen synthesis in early human gestation by aminoglutethimide in vivo.

    PubMed

    Rabe, T; Mösch, R; Franke, C; Nobakht, N; Runnebaum, B

    1983-03-01

    The inhibitory effect of d,l-aminoglutethimide (AG) on the synthesis of progesterone and estradiol in early human pregnancy (8th-12th week of gestation) was investigated in volunteers; control group (n = 11), AG group [1000 mg AG orally at test begin (n = 6)]. Venous blood samples were taken at the beginning of the test and 0.5, 1, 2, 4, 8 and 24 h thereafter. In controls, no significant changes in serum progesterone and estradiol could be observed during 24 h. In the AG group, a decrease in progesterone and estradiol could be observed within 1 h after the test began; lowest serum steroid concentrations were reached after 4 h. Relative to the initial values taken as 100%, the greatest decrease in progesterone ranged between 37 and 83%, 62 +/- 15% (means +/- SD)(n = 6); the greatest decrease in estradiol ranged between 32 and 78%, 51 +/- 17% (means +/- SD)(n = 6). Twenty four hours after AG treatment, both steroids reached similar concentrations to those found at test begin. No clinical signs (e.g. uterine bleeding, contractions) for the abortifacient action of AG were observed. In conclusion, a single dose of AG (1000 mg given orally) cannot induce a therapeutic abortion in early pregnancy. In accordance with in vitro studies, the inhibitory effect of AG on placental progesterone formation is due to an inhibition of mitochondrial cholesterol side chain cleavage. The decrease in estradiol is thought to be related to an inhibition of placental aromatase.

  14. Early Differentiation within the Animate Domain: Are Humans Something Special?

    ERIC Educational Resources Information Center

    Pauen, Sabina

    2000-01-01

    Two experiments investigated whether preverbal infants distinguish between humans and mammals. Study 1 found that 7-, 9-, and 11-month-olds distinguished humans from mammals in an object-examination task. Study 2 found that 7-month-olds but not 5-month-olds showed evidence for category discrimination with the 2-dimensional color photos of toy…

  15. Dynamics of thymus organogenesis and colonization in early human development

    PubMed Central

    Farley, Alison M.; Morris, Lucy X.; Vroegindeweij, Eric; Depreter, Marianne L. G.; Vaidya, Harsh; Stenhouse, Frances H.; Tomlinson, Simon R.; Anderson, Richard A.; Cupedo, Tom; Cornelissen, Jan J.; Blackburn, C. Clare

    2013-01-01

    The thymus is the central site of T-cell development and thus is of fundamental importance to the immune system, but little information exists regarding molecular regulation of thymus development in humans. Here we demonstrate, via spatial and temporal expression analyses, that the genetic mechanisms known to regulate mouse thymus organogenesis are conserved in humans. In addition, we provide molecular evidence that the human thymic epithelium derives solely from the third pharyngeal pouch, as in the mouse, in contrast to previous suggestions. Finally, we define the timing of onset of hematopoietic cell colonization and epithelial cell differentiation in the human thymic primordium, showing, unexpectedly, that the first colonizing hematopoietic cells are CD45+CD34int/-. Collectively, our data provide essential information for translation of principles established in the mouse to the human, and are of particular relevance to development of improved strategies for enhancing immune reconstitution in patients. PMID:23571219

  16. Friend or Foe? Early Social Evaluation of Human Interactions

    PubMed Central

    Buon, Marine; Jacob, Pierre; Margules, Sylvie; Brunet, Isabelle; Dutat, Michel; Cabrol, Dominique; Dupoux, Emmanuel

    2014-01-01

    We report evidence that 29-month-old toddlers and 10-month-old preverbal infants discriminate between two agents: a pro-social agent, who performs a positive (comforting) action on a human patient and a negative (harmful) action on an inanimate object, and an anti-social agent, who does the converse. The evidence shows that they prefer the former to the latter even though the agents perform the same bodily movements. Given that humans can cause physical harm to their conspecifics, we discuss this finding in light of the likely adaptive value of the ability to detect harmful human agents. PMID:24586355

  17. Cassava genome from a wild ancestor to cultivated varieties.

    PubMed

    Wang, Wenquan; Feng, Binxiao; Xiao, Jingfa; Xia, Zhiqiang; Zhou, Xincheng; Li, Pinghua; Zhang, Weixiong; Wang, Ying; Møller, Birger Lindberg; Zhang, Peng; Luo, Ming-Cheng; Xiao, Gong; Liu, Jingxing; Yang, Jun; Chen, Songbi; Rabinowicz, Pablo D; Chen, Xin; Zhang, Hong-Bin; Ceballos, Henan; Lou, Qunfeng; Zou, Meiling; Carvalho, Luiz J C B; Zeng, Changying; Xia, Jing; Sun, Shixiang; Fu, Yuhua; Wang, Haiyan; Lu, Cheng; Ruan, Mengbin; Zhou, Shuigeng; Wu, Zhicheng; Liu, Hui; Kannangara, Rubini Maya; Jørgensen, Kirsten; Neale, Rebecca Louise; Bonde, Maya; Heinz, Nanna; Zhu, Wenli; Wang, Shujuan; Zhang, Yang; Pan, Kun; Wen, Mingfu; Ma, Ping-An; Li, Zhengxu; Hu, Meizhen; Liao, Wenbin; Hu, Wenbin; Zhang, Shengkui; Pei, Jinli; Guo, Anping; Guo, Jianchun; Zhang, Jiaming; Zhang, Zhengwen; Ye, Jianqiu; Ou, Wenjun; Ma, Yaqin; Liu, Xinyue; Tallon, Luke J; Galens, Kevin; Ott, Sandra; Huang, Jie; Xue, Jingjing; An, Feifei; Yao, Qingqun; Lu, Xiaojing; Fregene, Martin; López-Lavalle, L Augusto Becerra; Wu, Jiajie; You, Frank M; Chen, Meili; Hu, Songnian; Wu, Guojiang; Zhong, Silin; Ling, Peng; Chen, Yeyuan; Wang, Qinghuang; Liu, Guodao; Liu, Bin; Li, Kaimian; Peng, Ming

    2014-01-01

    Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology. PMID:25300236

  18. Cassava genome from a wild ancestor to cultivated varieties

    PubMed Central

    Wang, Wenquan; Feng, Binxiao; Xiao, Jingfa; Xia, Zhiqiang; Zhou, Xincheng; Li, Pinghua; Zhang, Weixiong; Wang, Ying; Møller, Birger Lindberg; Zhang, Peng; Luo, Ming-Cheng; Xiao, Gong; Liu, Jingxing; Yang, Jun; Chen, Songbi; Rabinowicz, Pablo D.; Chen, Xin; Zhang, Hong-Bin; Ceballos, Henan; Lou, Qunfeng; Zou, Meiling; Carvalho, Luiz J.C.B.; Zeng, Changying; Xia, Jing; Sun, Shixiang; Fu, Yuhua; Wang, Haiyan; Lu, Cheng; Ruan, Mengbin; Zhou, Shuigeng; Wu, Zhicheng; Liu, Hui; Kannangara, Rubini Maya; Jørgensen, Kirsten; Neale, Rebecca Louise; Bonde, Maya; Heinz, Nanna; Zhu, Wenli; Wang, Shujuan; Zhang, Yang; Pan, Kun; Wen, Mingfu; Ma, Ping-An; Li, Zhengxu; Hu, Meizhen; Liao, Wenbin; Hu, Wenbin; Zhang, Shengkui; Pei, Jinli; Guo, Anping; Guo, Jianchun; Zhang, Jiaming; Zhang, Zhengwen; Ye, Jianqiu; Ou, Wenjun; Ma, Yaqin; Liu, Xinyue; Tallon, Luke J.; Galens, Kevin; Ott, Sandra; Huang, Jie; Xue, Jingjing; An, Feifei; Yao, Qingqun; Lu, Xiaojing; Fregene, Martin; López-Lavalle, L. Augusto Becerra; Wu, Jiajie; You, Frank M.; Chen, Meili; Hu, Songnian; Wu, Guojiang; Zhong, Silin; Ling, Peng; Chen, Yeyuan; Wang, Qinghuang; Liu, Guodao; Liu, Bin; Li, Kaimian; Peng, Ming

    2014-01-01

    Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology. PMID:25300236

  19. Fine specificity of cellular immune responses in humans to human cytomegalovirus immediate-early 1 protein.

    PubMed Central

    Alp, N J; Allport, T D; Van Zanten, J; Rodgers, B; Sissons, J G; Borysiewicz, L K

    1991-01-01

    Cell-mediated immunity is important in maintaining the virus-host equilibrium in persistent human cytomegalovirus (HCMV) infection. The HCMV 72-kDa major immediate early 1 protein (IE1) is a target for CD8+ cytotoxic T cells in humans, as is the equivalent 89-kDa protein in mouse. Less is known about responses against this protein by CD4+ T cells, which may be important as direct effector cells or helper cells for antibody and CD8+ responses. Proliferative-T-cell responses to HCMV IE1 were studied in normal seropositive subjects. Peripheral blood mononuclear cells from 85% of seropositive subjects proliferated in response to HCMV from infected fibroblasts, and of these, 73% responded to recombinant baculovirus IE1. Responding cells were predominantly CD3+ CD4+. IE1 antigen preparations, including baculovirus recombinant protein, transfected rat cell nuclei, and synthetic peptides, induced IE1-specific T-cell lines which cross-reacted between the preparations. The fine specificity of these IE1-specific T-cell lines was studied by using overlapping synthetic peptides encompassing the entire sequence of the IE1 protein. The regions of the IE1 molecule recognized were identified and these varied between individuals, possibly reflecting differences in major histocompatibility complex (MHC) class II haplotype. In one subject, the peptide specificities of proliferative and MHC class I-restricted cytotoxic determinants on IE1 were spatially distinct. Thus, no single immunodominant T-cell determinant within HCMV IE1 was identified, suggesting that multiple peptides or a region of the 72-kDa IE1 protein would be required to induce specific T-cell responses in humans. PMID:1714519

  20. Early-season avian deaths from West Nile virus as warnings of human infection

    USGS Publications Warehouse

    Guptill, S.C.; Julian, K.G.; Campbell, G.L.; Price, S.D.; Marfin, A.A.

    2003-01-01

    An analysis of 2001 and 2002 West Nile virus (WNV) surveillance data shows that counties that report WNV-infected dead birds early in the transmission season are more likely to report subsequent WNV disease cases in humans than are counties that do not report early WNV-infected dead birds.

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

    PubMed Central

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

    2009-01-01

    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 human fossils with that in other groups of fossil Homo and recent modern humans. Variation is assessed as the mean-squared Procrustes distance from the group average shape in a representation based on several hundred neurocranial landmarks and semilandmarks. We find that the early modern group has more shape variation than any other group in our sample, which covers 1.8 million years, and that they are morphologically similar to recent modern humans of diverse geographically dispersed populations but not to archaic groups. Of the currently competing models of modern human origins, some are inconsistent with these findings. Rather than a single out-of-Africa dispersal scenario, we suggest that early modern humans were already divided into different populations in Pleistocene Africa, after which there followed a complex migration pattern. Our conclusions bear implications for the inference of ancient human demography from genetic models and emphasize the importance of focusing research on those early modern humans, in particular, in Africa. PMID:19307568

  2. Genomic evidence for large, long-lived ancestors to placental mammals.

    PubMed

    Romiguier, J; Ranwez, V; Douzery, E J P; Galtier, N

    2013-01-01

    It is widely assumed that our mammalian ancestors, which lived in the Cretaceous era, were tiny animals that survived massive asteroid impacts in shelters and evolved into modern forms after dinosaurs went extinct, 65 Ma. The small size of most Mesozoic mammalian fossils essentially supports this view. Paleontology, however, is not conclusive regarding the ancestry of extant mammals, because Cretaceous and Paleocene fossils are not easily linked to modern lineages. Here, we use full-genome data to estimate the longevity and body mass of early placental mammals. Analyzing 36 fully sequenced mammalian genomes, we reconstruct two aspects of the ancestral genome dynamics, namely GC-content evolution and nonsynonymous over synonymous rate ratio. Linking these molecular evolutionary processes to life-history traits in modern species, we estimate that early placental mammals had a life span above 25 years and a body mass above 1 kg. This is similar to current primates, cetartiodactyls, or carnivores, but markedly different from mice or shrews, challenging the dominant view about mammalian origin and evolution. Our results imply that long-lived mammals existed in the Cretaceous era and were the most successful in evolution, opening new perspectives about the conditions for survival to the Cretaceous-Tertiary crisis.

  3. Structure–Function Relationships of Glycoprotein Hormones and Their Subunits’ Ancestors

    PubMed Central

    Cahoreau, Claire; Klett, Danièle; Combarnous, Yves

    2015-01-01

    Glycoprotein hormones (GPHs) are the most complex molecules with hormonal activity. They exist only in vertebrates but the genes encoding their subunits’ ancestors are found in most vertebrate and invertebrate species although their roles are still unknown. In the present report, we review the available structural and functional data concerning GPHs and their subunits’ ancestors. PMID:25767463

  4. The Malthusian parameter of ascents: What prevents the exponential increase of one’s ancestors?

    PubMed Central

    Ohno, Susumu

    1996-01-01

    The reason that the indefinite exponential increase in the number of one’s ancestors does not take place is found in the law of sibling interference, which can be expressed by the following simple equation:\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}\\begin{matrix}{\\mathit{N}}_{{\\mathit{n}}} \\enskip & \\\\ {\\mathit{{\\blacksquare}}} \\enskip & \\\\ {\\mathit{ASZ}} \\enskip & \\end{matrix} {\\mathrm{\\hspace{.167em}{\\times}\\hspace{.167em}2\\hspace{.167em}=\\hspace{.167em}}}{\\mathit{N_{n+1},}}\\end{equation*}\\end{document} where Nn is the number of ancestors in the nth generation, ASZ is the average sibling size of these ancestors, and Nn+1 is the number of ancestors in the next older generation (n + 1). Accordingly, the exponential increase in the number of one’s ancestors is an initial anomaly that occurs while ASZ remains at 1. Once ASZ begins to exceed 1, the rate of increase in the number of ancestors is progressively curtailed, falling further and further behind the exponential increase rate. Eventually, ASZ reaches 2, and at that point, the number of ancestors stops increasing for two generations. These two generations, named AN SA and AN SA + 1, are the most critical in the ancestry, for one’s ancestors at that point come to represent all the progeny-produced adults of the entire ancestral population. Thereafter, the fate of one’s ancestors becomes the fate of the entire population. If the population to which one belongs is a successful, slowly expanding one, the number of ancestors would slowly decline as you move toward the remote past. This is because ABZ would exceed 2. Only when ABZ is less than 2 would the number of ancestors increase beyond the AN SA and AN SA + 1 generations. Since the above is an indication of a failing population on the way to

  5. Human Ecology and Television in Early Childhood Education.

    ERIC Educational Resources Information Center

    Schleicher, Klaus

    A human ecological approach to the study of children's television viewing raises questions that researchers have largely neglected. Does television influence the interaction patterns of socializing agents with children and with one another? Are there long-term, psychological consequences of unintegrated and competing influences from television and…

  6. Intestinal microbiology in early life: specific prebiotics can have similar functionalities as human-milk oligosaccharides.

    PubMed

    Oozeer, Raish; van Limpt, Kees; Ludwig, Thomas; Ben Amor, Kaouther; Martin, Rocio; Wind, Richèle D; Boehm, Günther; Knol, Jan

    2013-08-01

    Human milk is generally accepted as the best nutrition for newborns and has been shown to support the optimal growth and development of infants. On the basis of scientific insights from human-milk research, a specific mixture of nondigestible oligosaccharides has been developed, with the aim to improve the intestinal microbiota in early life. The mixture has been extensively studied and has been shown to be safe and to have potential health benefits that are similar to those of human milk. The specific mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides has been found to affect the development of early microbiota and to increase the Bifidobacterium amounts as observed in human-milk-fed infants. The resulting gut ecophysiology is characterized by high concentrations of lactate, a slightly acidic pH, and specific short-chain fatty acid profiles, which are high in acetate and low in butyrate and propionate. Here, we have summarized the main findings of dietary interventions with these specific oligosaccharides on the gut microbiota in early life. The gut ecophysiology in early life may have consequences for the metabolic, immunologic, and even neurologic development of the child because reports increasingly substantiate the important function of gut microbes in human health. This review highlights major findings in the field of early gut colonization and the potential impact of early nutrition in healthy growth and development.

  7. Early detection of intentional harm in the human amygdala.

    PubMed

    Hesse, Eugenia; Mikulan, Ezequiel; Decety, Jean; Sigman, Mariano; Garcia, María del Carmen; Silva, Walter; Ciraolo, Carlos; Vaucheret, Esteban; Baglivo, Fabricio; Huepe, David; Lopez, Vladimir; Manes, Facundo; Bekinschtein, Tristan A; Ibanez, Agustin

    2016-01-01

    A decisive element of moral cognition is the detection of harm and its assessment as intentional or unintentional. Moral cognition engages brain networks supporting mentalizing, intentionality, empathic concern and evaluation. These networks rely on the amygdala as a critical hub, likely through frontotemporal connections indexing stimulus salience. We assessed inferences about perceived harm using a paradigm validated through functional magnetic resonance imaging, eye-tracking and electroencephalogram recordings. During the task, we measured local field potentials in three patients with depth electrodes (n = 115) placed in the amygdala and in several frontal, temporal, and parietal locations. Direct electrophysiological recordings demonstrate that intentional harm induces early activity in the amygdala (<200 ms), which--in turn--predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classification of events as intentional. Moreover, connectivity analysis showed that intentional harm induced stronger frontotemporal information sharing at early stages. Results support the 'many roads' view of the amygdala and highlight its role in the rapid encoding of intention and salience--critical components of mentalizing and moral evaluation. PMID:26608745

  8. Electrophysiological evidence for an early processing of human voices

    PubMed Central

    Charest, Ian; Pernet, Cyril R; Rousselet, Guillaume A; Quiñones, Ileana; Latinus, Marianne; Fillion-Bilodeau, Sarah; Chartrand, Jean-Pierre; Belin, Pascal

    2009-01-01

    Background Previous electrophysiological studies have identified a "voice specific response" (VSR) peaking around 320 ms after stimulus onset, a latency markedly longer than the 70 ms needed to discriminate living from non-living sound sources and the 150 ms to 200 ms needed for the processing of voice paralinguistic qualities. In the present study, we investigated whether an early electrophysiological difference between voice and non-voice stimuli could be observed. Results ERPs were recorded from 32 healthy volunteers who listened to 200 ms long stimuli from three sound categories - voices, bird songs and environmental sounds - whilst performing a pure-tone detection task. ERP analyses revealed voice/non-voice amplitude differences emerging as early as 164 ms post stimulus onset and peaking around 200 ms on fronto-temporal (positivity) and occipital (negativity) electrodes. Conclusion Our electrophysiological results suggest a rapid brain discrimination of sounds of voice, termed the "fronto-temporal positivity to voices" (FTPV), at latencies comparable to the well-known face-preferential N170. PMID:19843323

  9. No Evidence of Neandertal mtDNA Contribution to Early Modern Humans

    PubMed Central

    2004-01-01

    The retrieval of mitochondrial DNA (mtDNA) sequences from four Neandertal fossils from Germany, Russia, and Croatia has demonstrated that these individuals carried closely related mtDNAs that are not found among current humans. However, these results do not definitively resolve the question of a possible Neandertal contribution to the gene pool of modern humans since such a contribution might have been erased by genetic drift or by the continuous influx of modern human DNA into the Neandertal gene pool. A further concern is that if some Neandertals carried mtDNA sequences similar to contemporaneous humans, such sequences may be erroneously regarded as modern contaminations when retrieved from fossils. Here we address these issues by the analysis of 24 Neandertal and 40 early modern human remains. The biomolecular preservation of four Neandertals and of five early modern humans was good enough to suggest the preservation of DNA. All four Neandertals yielded mtDNA sequences similar to those previously determined from Neandertal individuals, whereas none of the five early modern humans contained such mtDNA sequences. In combination with current mtDNA data, this excludes any large genetic contribution by Neandertals to early modern humans, but does not rule out the possibility of a smaller contribution. PMID:15024415

  10. Bayesian inference of sampled ancestor trees for epidemiology and fossil calibration.

    PubMed

    Gavryushkina, Alexandra; Welch, David; Stadler, Tanja; Drummond, Alexei J

    2014-12-01

    Phylogenetic analyses which include fossils or molecular sequences that are sampled through time require models that allow one sample to be a direct ancestor of another sample. As previously available phylogenetic inference tools assume that all samples are tips, they do not allow for this possibility. We have developed and implemented a Bayesian Markov Chain Monte Carlo (MCMC) algorithm to infer what we call sampled ancestor trees, that is, trees in which sampled individuals can be direct ancestors of other sampled individuals. We use a family of birth-death models where individuals may remain in the tree process after sampling, in particular we extend the birth-death skyline model [Stadler et al., 2013] to sampled ancestor trees. This method allows the detection of sampled ancestors as well as estimation of the probability that an individual will be removed from the process when it is sampled. We show that even if sampled ancestors are not of specific interest in an analysis, failing to account for them leads to significant bias in parameter estimates. We also show that sampled ancestor birth-death models where every sample comes from a different time point are non-identifiable and thus require one parameter to be known in order to infer other parameters. We apply our phylogenetic inference accounting for sampled ancestors to epidemiological data, where the possibility of sampled ancestors enables us to identify individuals that infected other individuals after being sampled and to infer fundamental epidemiological parameters. We also apply the method to infer divergence times and diversification rates when fossils are included along with extant species samples, so that fossilisation events are modelled as a part of the tree branching process. Such modelling has many advantages as argued in the literature. The sampler is available as an open-source BEAST2 package (https://github.com/CompEvol/sampled-ancestors). PMID:25474353

  11. Bayesian Inference of Sampled Ancestor Trees for Epidemiology and Fossil Calibration

    PubMed Central

    Gavryushkina, Alexandra; Welch, David; Stadler, Tanja; Drummond, Alexei J.

    2014-01-01

    Phylogenetic analyses which include fossils or molecular sequences that are sampled through time require models that allow one sample to be a direct ancestor of another sample. As previously available phylogenetic inference tools assume that all samples are tips, they do not allow for this possibility. We have developed and implemented a Bayesian Markov Chain Monte Carlo (MCMC) algorithm to infer what we call sampled ancestor trees, that is, trees in which sampled individuals can be direct ancestors of other sampled individuals. We use a family of birth-death models where individuals may remain in the tree process after sampling, in particular we extend the birth-death skyline model [Stadler et al., 2013] to sampled ancestor trees. This method allows the detection of sampled ancestors as well as estimation of the probability that an individual will be removed from the process when it is sampled. We show that even if sampled ancestors are not of specific interest in an analysis, failing to account for them leads to significant bias in parameter estimates. We also show that sampled ancestor birth-death models where every sample comes from a different time point are non-identifiable and thus require one parameter to be known in order to infer other parameters. We apply our phylogenetic inference accounting for sampled ancestors to epidemiological data, where the possibility of sampled ancestors enables us to identify individuals that infected other individuals after being sampled and to infer fundamental epidemiological parameters. We also apply the method to infer divergence times and diversification rates when fossils are included along with extant species samples, so that fossilisation events are modelled as a part of the tree branching process. Such modelling has many advantages as argued in the literature. The sampler is available as an open-source BEAST2 package (https://github.com/CompEvol/sampled-ancestors). PMID:25474353

  12. Discontinuity of Human Presence at Atapuerca during the Early Middle Pleistocene: A Matter of Ecological Competition?

    PubMed Central

    Rodríguez-Gómez, Guillermo; Mateos, Ana; Martín-González, Jesús Angel; Blasco, Ruth; Rosell, Jordi; Rodríguez, Jesús

    2014-01-01

    Increasing evidence suggests that the European human settlement is older than 1.2 Ma. However, there is a fierce debate about the continuity or discontinuity of the early human settlement of Europe. In particular, evidence of human presence in the interval 0.7−0.5 Ma is scarce in comparison with evidence for the previous and later periods. Here, we present a case study in which the environmental conditions at Sierra de Atapuerca in the early Middle Pleistocene, a period without evidence of human presence, are compared with the conditions in the previous period, for which a relatively intense human occupation is documented. With this objective in mind, the available resources for a human population and the intensity of competition between secondary consumers during the two periods are compared using a mathematical model. The Gran Dolina site TD8 level, dated to 0.7−0.6 Ma, is taken as representative of the period during which Atapuerca was apparently not occupied by humans. Conditions at TD8 are compared with those of the previous period, represented by the TD6-2 level, which has yielded abundant evidence of intense human occupation. The results show that survival opportunities for a hypothetical human population were lower at TD8 than they were at TD6-2. Increased resource competition between secondary consumers arises as a possible explanation for the absence of human occupation at Atapuerca in the early Middle Pleistocene. PMID:25054305

  13. Whence genes in pieces: reconstruction of the exon-intron gene structures of the last eukaryotic common ancestor and other ancestral eukaryotes.

    PubMed

    Koonin, Eugene V; Csuros, Miklos; Rogozin, Igor B

    2013-01-01

    In eukaryotes, protein-coding sequences are interrupted by non-coding sequences known as introns. During mRNA maturation, introns are excised by the spliceosome and the coding regions, exons, are spliced to form the mature coding region. The intron densities widely differ between eukaryotic lineages, from 6 to 7 introns per kb of coding sequence in vertebrates, some invertebrates and green plants, to only a few introns across the entire genome in many unicellular eukaryotes. Evolutionary reconstructions using maximum likelihood methods suggest intron-rich ancestors for each major group of eukaryotes. For the last common ancestor of animals, the highest intron density of all extant and extinct eukaryotes was inferred, at 120-130% of the human intron density. Furthermore, an intron density within 53-74% of the human values was inferred for the last eukaryotic common ancestor. Accordingly, evolution of eukaryotic genes in all lines of descent involved primarily intron loss, with substantial gain only at the bases of several branches including plants and animals. These conclusions have substantial biological implications indicating that the common ancestor of all modern eukaryotes was a complex organism with a gene architecture resembling those in multicellular organisms. Alternative splicing most likely initially appeared as an inevitable result of splicing errors and only later was employed to generate structural and functional diversification of proteins.

  14. Strong gender differences in reproductive success variance, and the times to the most recent common ancestors.

    PubMed

    Favre, Maroussia; Sornette, Didier

    2012-10-01

    The Time to the Most Recent Common Ancestor (TMRCA) based on human mitochondrial DNA (mtDNA) is estimated to be twice that based on the non-recombining part of the Y chromosome (NRY). These TMRCAs have special demographic implications because mtDNA is transmitted only from mother to child, while NRY is passed along from father to son. Therefore, the former locus reflects female history, and the latter, male history. To investigate what caused the two-to-one female-male TMRCA ratio r(F/M)=T(F)/T(M) in humans, we develop a forward-looking agent-based model (ABM) with overlapping generations. Our ABM simulates agents with individual life cycles, including life events such as reaching maturity or menopause. We implemented two main mating systems: polygynandry and polygyny with different degrees in between. In each mating system, the male population can be either homogeneous or heterogeneous. In the latter case, some males are 'alphas' and others are 'betas', which reflects the extent to which they are favored by female mates. A heterogeneous male population implies a competition among males with the purpose of signaling as alpha males. The introduction of a heterogeneous male population is found to reduce by a factor 2 the probability of finding equal female and male TMRCAs and shifts the distribution of r(F/M) to higher values. In order to account for the empirical observation of the factor 2, a high level of heterogeneity in the male population is needed: less than half the males can be alphas and betas can have at most half the fitness of alphas for the TMRCA ratio to depart significantly from 1. In addition, we find that, in the modes that maximize the probability of having 1.5ancestors. We also tested the effect of sex-biased migration and sex-specific death rates and found that these are unlikely to explain alone the sex-biased TMRCA ratio observed in humans. Our results support the view

  15. A theoretical framework for early human studies: uncertainty, intervention ensembles, and boundaries

    PubMed Central

    2012-01-01

    Clinical development of novel therapeutics begins with a coordinated sequence of early phase clinical trials. Such early human studies confront a series of methodological and ethical challenges. In what follows, I propose a theoretical framework for early human studies aimed at informing the negotiation of these challenges. At the outset of clinical development, researchers confront a virtually undifferentiated landscape of uncertainty with respect to three variables: outcomes, their probability of occurrence, and operation dimensions needed to effectuate favorable outcomes. Early human trials transform this uncertain landscape into one where there are grounds for belief about risk and benefit for various combined operation dimensions. To accomplish this, studies set out with two aims. First, they identify a set of operation dimensions that, when combined as a package (intervention ensemble), elicits a reasonable probability of a target outcome. Second, they define the boundaries of dimension values within an intervention ensemble. This latter aim entails exposing at least some volunteers in early studies to treatments that are inactive or excessive. I provide examples that illustrate the way early human studies discover and delimit intervention ensembles, and close by offering some implications of this framework for ethics, methodology, and efficiency in clinical development of new interventions. PMID:22999017

  16. A theoretical framework for early human studies: uncertainty, intervention ensembles, and boundaries.

    PubMed

    Kimmelman, Jonathan

    2012-01-01

    Clinical development of novel therapeutics begins with a coordinated sequence of early phase clinical trials. Such early human studies confront a series of methodological and ethical challenges. In what follows, I propose a theoretical framework for early human studies aimed at informing the negotiation of these challenges. At the outset of clinical development, researchers confront a virtually undifferentiated landscape of uncertainty with respect to three variables: outcomes, their probability of occurrence, and operation dimensions needed to effectuate favorable outcomes. Early human trials transform this uncertain landscape into one where there are grounds for belief about risk and benefit for various combined operation dimensions. To accomplish this, studies set out with two aims. First, they identify a set of operation dimensions that, when combined as a package (intervention ensemble), elicits a reasonable probability of a target outcome. Second, they define the boundaries of dimension values within an intervention ensemble. This latter aim entails exposing at least some volunteers in early studies to treatments that are inactive or excessive. I provide examples that illustrate the way early human studies discover and delimit intervention ensembles, and close by offering some implications of this framework for ethics, methodology, and efficiency in clinical development of new interventions.

  17. Edwin Grant Dexter: an early researcher in human behavioral biometeorology.

    PubMed

    Stewart, Alan E

    2015-06-01

    Edwin Grant Dexter (1868-1938) was one of the first researchers to study empirically the effects of specific weather conditions on human behavior. Dexter (1904) published his findings in a book, Weather influences. The author's purposes in this article were to (1) describe briefly Dexter's professional life and examine the historical contexts and motivations that led Dexter to conduct some of the first empirical behavioral biometeorological studies of the time, (2) describe the methods Dexter used to examine weather-behavior relationships and briefly characterize the results that he reported in Weather influences, and (3) provide a historical analysis of Dexter's work and assess its significance for human behavioral biometeorology. Dexter's Weather influences, while demonstrating an exemplary approach to weather, health, and behavior relationships, came at the end of a long era of such studies, as health, social, and meteorological sciences were turning to different paradigms to advance their fields. For these reasons, Dexter's approach and contributions may not have been fully recognized at the time and are, consequently, worthy of consideration by contemporary biometeorologists.

  18. Edwin Grant Dexter: an early researcher in human behavioral biometeorology

    NASA Astrophysics Data System (ADS)

    Stewart, Alan E.

    2014-09-01

    Edwin Grant Dexter (1868-1938) was one of the first researchers to study empirically the effects of specific weather conditions on human behavior. Dexter (1904) published his findings in a book, Weather influences. The author's purposes in this article were to (1) describe briefly Dexter's professional life and examine the historical contexts and motivations that led Dexter to conduct some of the first empirical behavioral biometeorological studies of the time, (2) describe the methods Dexter used to examine weather-behavior relationships and briefly characterize the results that he reported in Weather influences, and (3) provide a historical analysis of Dexter's work and assess its significance for human behavioral biometeorology. Dexter's Weather influences, while demonstrating an exemplary approach to weather, health, and behavior relationships, came at the end of a long era of such studies, as health, social, and meteorological sciences were turning to different paradigms to advance their fields. For these reasons, Dexter's approach and contributions may not have been fully recognized at the time and are, consequently, worthy of consideration by contemporary biometeorologists.

  19. Edwin Grant Dexter: an early researcher in human behavioral biometeorology

    NASA Astrophysics Data System (ADS)

    Stewart, Alan E.

    2015-06-01

    Edwin Grant Dexter (1868-1938) was one of the first researchers to study empirically the effects of specific weather conditions on human behavior. Dexter (1904) published his findings in a book, Weather influences. The author's purposes in this article were to (1) describe briefly Dexter's professional life and examine the historical contexts and motivations that led Dexter to conduct some of the first empirical behavioral biometeorological studies of the time, (2) describe the methods Dexter used to examine weather-behavior relationships and briefly characterize the results that he reported in Weather influences, and (3) provide a historical analysis of Dexter's work and assess its significance for human behavioral biometeorology. Dexter's Weather influences, while demonstrating an exemplary approach to weather, health, and behavior relationships, came at the end of a long era of such studies, as health, social, and meteorological sciences were turning to different paradigms to advance their fields. For these reasons, Dexter's approach and contributions may not have been fully recognized at the time and are, consequently, worthy of consideration by contemporary biometeorologists.

  20. Early morphological changes in organ cultured human corneal endothelium.

    PubMed

    Sperling, S

    1978-10-01

    Nineteen human cadaver corneas with few damaged endothelial cells were incubated under tissue culture conditions for time periods ranging from five min to 48 h. Morphological alterations of the endothelial cells were studied in whole wet mounts stained by alizarine red-alkohol-trypane blue and by scanning electron microscopy. Joint meetings of three cells are characteristic for normal corneal endothelium. After 15--60 min of incubation, damaged cells were expelled from the coherent cell sheet by expanding neighbouring cells. Joint meetings of 5--8 expanding cells were formed. After 24 h of incubation, joint meetings of four cells were the dominating morphological abnormality. Morphological changes during reduction of the numbers of cells in joint meetings are described.

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

    PubMed Central

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

    2015-01-01

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

  2. In search of the last common ancestor: new findings on wild chimpanzees

    PubMed Central

    McGrew, W. C.

    2010-01-01

    Modelling the behaviour of extinct hominins is essential in order to devise useful hypotheses of our species' evolutionary origins for testing in the palaeontological and archaeological records. One approach is to model the last common ancestor (LCA) of living apes and humans, based on current ethological and ecological knowledge of our closest living relations. Such referential modelling is based on rigorous, ongoing field studies of the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). This paper reviews recent findings from nature, focusing on those with direct implications for hominin evolution, e.g. apes, using elementary technology to access basic resources such as food and water, or sheltering in caves or bathing as thermoregulatory adaptations. I give preference to studies that directly address key issues, such as whether stone artefacts are detectible before the Oldowan, based on the percussive technology of hammer and anvil use by living apes. Detailed comparative studies of chimpanzees living in varied habitats, from rainforest to savannah, reveal that some behavioural patterns are universal (e.g. shelter construction), while others show marked (e.g. extractive foraging) or nuanced (e.g. courtship) cross-populational variation. These findings allow us to distinguish between retained, primitive traits of the LCA versus derived ones in the human lineage. PMID:20855301

  3. Early Preferential Responses to Fear Stimuli in Human Right Dorsal Visual Stream--A Meg Study.

    PubMed

    Meeren, Hanneke K M; Hadjikhani, Nouchine; Ahlfors, Seppo P; Hämäläinen, Matti S; de Gelder, Beatrice

    2016-04-20

    Emotional expressions of others are salient biological stimuli that automatically capture attention and prepare us for action. We investigated the early cortical dynamics of automatic visual discrimination of fearful body expressions by monitoring cortical activity using magnetoencephalography. We show that right parietal cortex distinguishes between fearful and neutral bodies as early as 80-ms after stimulus onset, providing the first evidence for a fast emotion-attention-action link through human dorsal visual stream.

  4. On the origin and evolution of thermophily: reconstruction of functional precambrian enzymes from ancestors of Bacillus.

    PubMed

    Hobbs, Joanne K; Shepherd, Charis; Saul, David J; Demetras, Nicholas J; Haaning, Svend; Monk, Colin R; Daniel, Roy M; Arcus, Vickery L

    2012-02-01

    Thermophily is thought to be a primitive trait, characteristic of early forms of life on Earth, that has been gradually lost over evolutionary time. The genus Bacillus provides an ideal model for studying the evolution of thermophily as it is an ancient taxon and its contemporary species inhabit a range of thermal environments. The thermostability of reconstructed ancestral proteins has been used as a proxy for ancient thermal adaptation. The reconstruction of ancestral "enzymes" has the added advantages of demonstrable activity, which acts as an internal control for accurate inference, and providing insights into the evolution of enzymatic catalysis. Here, we report the reconstruction of the structurally complex core metabolic enzyme LeuB (3-isopropylmalate dehydrogenase, E. C. 1.1.1.85) from the last common ancestor (LCA) of Bacillus using both maximum likelihood (ML) and Bayesian inference. ML LeuB from the LCA of Bacillus shares only 76% sequence identity with its closest contemporary homolog, yet it is fully functional, thermophilic, and exhibits high values for k(cat), k(cat)/K(M), and ΔG(‡) for unfolding. The Bayesian version of this enzyme is also thermophilic but exhibits anomalous catalytic kinetics. We have determined the 3D structure of the ML enzyme and found that it is more closely aligned with LeuB from deeply branching bacteria, such as Thermotoga maritima, than contemporary Bacillus species. To investigate the evolution of thermophily, three descendents of LeuB from the LCA of Bacillus were also reconstructed. They reveal a fluctuating trend in thermal evolution, with a temporal adaptation toward mesophily followed by a more recent return to thermophily. Structural analysis suggests that the determinants of thermophily in LeuB from the LCA of Bacillus and the most recent ancestor are distinct and that thermophily has arisen in this genus at least twice via independent evolutionary paths. Our results add significant fluctuations to the broad

  5. On the origin and evolution of thermophily: reconstruction of functional precambrian enzymes from ancestors of Bacillus.

    PubMed

    Hobbs, Joanne K; Shepherd, Charis; Saul, David J; Demetras, Nicholas J; Haaning, Svend; Monk, Colin R; Daniel, Roy M; Arcus, Vickery L

    2012-02-01

    Thermophily is thought to be a primitive trait, characteristic of early forms of life on Earth, that has been gradually lost over evolutionary time. The genus Bacillus provides an ideal model for studying the evolution of thermophily as it is an ancient taxon and its contemporary species inhabit a range of thermal environments. The thermostability of reconstructed ancestral proteins has been used as a proxy for ancient thermal adaptation. The reconstruction of ancestral "enzymes" has the added advantages of demonstrable activity, which acts as an internal control for accurate inference, and providing insights into the evolution of enzymatic catalysis. Here, we report the reconstruction of the structurally complex core metabolic enzyme LeuB (3-isopropylmalate dehydrogenase, E. C. 1.1.1.85) from the last common ancestor (LCA) of Bacillus using both maximum likelihood (ML) and Bayesian inference. ML LeuB from the LCA of Bacillus shares only 76% sequence identity with its closest contemporary homolog, yet it is fully functional, thermophilic, and exhibits high values for k(cat), k(cat)/K(M), and ΔG(‡) for unfolding. The Bayesian version of this enzyme is also thermophilic but exhibits anomalous catalytic kinetics. We have determined the 3D structure of the ML enzyme and found that it is more closely aligned with LeuB from deeply branching bacteria, such as Thermotoga maritima, than contemporary Bacillus species. To investigate the evolution of thermophily, three descendents of LeuB from the LCA of Bacillus were also reconstructed. They reveal a fluctuating trend in thermal evolution, with a temporal adaptation toward mesophily followed by a more recent return to thermophily. Structural analysis suggests that the determinants of thermophily in LeuB from the LCA of Bacillus and the most recent ancestor are distinct and that thermophily has arisen in this genus at least twice via independent evolutionary paths. Our results add significant fluctuations to the broad

  6. Repolarisation and refractoriness during early ischaemia in humans

    PubMed Central

    Sutton, P; Taggart, P; Opthof, T; Coronel, R; Trimlett, R; Pugsley, W; Kallis, P

    2000-01-01

    OBJECTIVES—To determine whether effective refractory period (ERP) shortens or lengthens in the first minutes of ischaemia in humans, and the relation between ERP changes and action potential duration (APD).
METHODS—ERP and monophasic action potential duration (MAPD) were measured from a single left ventricular epicardial site in 26 patients undergoing coronary artery surgery. Cardiopulmonary bypass was instituted and normothermia maintained. Refractory period was determined by the extrastimulus technique at a basic cycle length of 500 ms, at four times (group 1, 15 patients) or two times (group 2, 11 patients) the preischaemic diastolic threshold. A three minute period of ischaemia was instituted by aortic cross clamping between the input from the pump oxygenator and the heart.
RESULTS—After three minutes of ischaemia, mean (SEM) ERP lengthened from 232 (5) ms (control) to 246 (7) ms (p < 0.005) in group 1, and from 256 (10) ms (control) to 348 (25) ms (p < 0.005) in group 2. In the same time MAPD shortened from 256 (5) ms (control) to 189 (9) ms (p < 0.001) with no difference between groups. Thus postrepolarisation refractoriness developed during ischaemia. Before ischaemia, ERP showed a good correlation with APD (R2 = 0.64) but by one minute of ischaemia the correlation was poor (R2 = 0.29).
CONCLUSIONS—These results show that during the first three minutes of global ischaemia in patients with coronary artery disease: (1) ERP lengthened in response to both a low and a high stimulus strength; and (2) there was a good correlation between ERP and APD before ischaemia, which was lost by one minute as APD decreased and ERP increased. These findings may have important implications in arrhythmogenesis.


Keywords: refractoriness; ischaemia; repolarisation PMID:10995401

  7. Evolution of human brain functions: the functional structure of human consciousness.

    PubMed

    Cloninger, C Robert

    2009-11-01

    The functional structure of self-aware consciousness in human beings is described based on the evolution of human brain functions. Prior work on heritable temperament and character traits is extended to account for the quantum-like and holographic properties (i.e. parts elicit wholes) of self-aware consciousness. Cladistic analysis is used to identify the succession of ancestors leading to human beings. The functional capacities that emerge along this lineage of ancestors are described. The ecological context in which each cladogenesis occurred is described to illustrate the shifting balance of evolution as a complex adaptive system. Comparative neuroanatomy is reviewed to identify the brain structures and networks that emerged coincident with the emergent brain functions. Individual differences in human temperament traits were well developed in the common ancestor shared by reptiles and humans. Neocortical development in mammals proceeded in five major transitions: from early reptiles to early mammals, early primates, simians, early Homo, and modern Homo sapiens. These transitions provide the foundation for human self-awareness related to sexuality, materiality, emotionality, intellectuality, and spirituality, respectively. The functional structure of human self-aware consciousness is concerned with the regulation of five planes of being: sexuality, materiality, emotionality, intellectuality, and spirituality. Each plane elaborates neocortical functions organized around one of the five special senses. The interactions among these five planes gives rise to a 5 x 5 matrix of subplanes, which are functions that coarsely describe the focus of neocortical regulation. Each of these 25 neocortical functions regulates each of five basic motives or drives that can be measured as temperaments or basic emotions related to fear, anger, disgust, surprise, and happiness/sadness. The resulting 5 x 5 x 5 matrix of human characteristics provides a general and testable model of the

  8. Apparatus Named after Our Academic Ancestors--II

    ERIC Educational Resources Information Center

    Greenslade, Thomas B., Jr.

    2011-01-01

    In my previous article on apparatus named after physicists and physics teachers, I discussed five relatively common pieces of apparatus from the 1875-1910 era. Now I will go back to the 18th and early-19th centuries to discuss eponymous apparatus that we are still using in lecture demonstrations. [For Part I, see EJ912907.

  9. Apparatus Named After Our Academic Ancestors — II

    NASA Astrophysics Data System (ADS)

    Greenslade, Thomas B.

    2011-01-01

    In my previous article on apparatus named after physicists and physics teachers, I discussed five relatively common pieces of apparatus from the 1875-1910 era. Now I will go back to the 18th and early-19th centuries to discuss eponymous2 apparatus that we are still using in lecture demonstrations.

  10. High early life mortality in free-ranging dogs is largely influenced by humans

    PubMed Central

    Paul, Manabi; Sen Majumder, Sreejani; Sau, Shubhra; Nandi, Anjan K.; Bhadra, Anindita

    2016-01-01

    Free-ranging dogs are a ubiquitous part of human habitations in many developing countries, leading a life of scavengers dependent on human wastes for survival. The effective management of free-ranging dogs calls for understanding of their population dynamics. Life expectancy at birth and early life mortality are important factors that shape life-histories of mammals. We carried out a five year-long census based study in seven locations of West Bengal, India, to understand the pattern of population growth and factors affecting early life mortality in free-ranging dogs. We observed high rates of mortality, with only ~19% of the 364 pups from 95 observed litters surviving till the reproductive age; 63% of total mortality being human influenced. While living near people increases resource availability for dogs, it also has deep adverse impacts on their population growth, making the dog-human relationship on streets highly complex. PMID:26804633

  11. The ancestor of extant Japanese fancy mice contributed to the mosaic genomes of classical inbred strains.

    PubMed

    Takada, Toyoyuki; Ebata, Toshinobu; Noguchi, Hideki; Keane, Thomas M; Adams, David J; Narita, Takanori; Shin-I, Tadasu; Fujisawa, Hironori; Toyoda, Atsushi; Abe, Kuniya; Obata, Yuichi; Sakaki, Yoshiyuki; Moriwaki, Kazuo; Fujiyama, Asao; Kohara, Yuji; Shiroishi, Toshihiko

    2013-08-01

    Commonly used classical inbred mouse strains have mosaic genomes with sequences from different subspecific origins. Their genomes are derived predominantly from the Western European subspecies Mus musculus domesticus, with the remaining sequences derived mostly from the Japanese subspecies Mus musculus molossinus. However, it remains unknown how this intersubspecific genome introgression occurred during the establishment of classical inbred strains. In this study, we resequenced the genomes of two M. m. molossinus-derived inbred strains, MSM/Ms and JF1/Ms. MSM/Ms originated from Japanese wild mice, and the ancestry of JF1/Ms was originally found in Europe and then transferred to Japan. We compared the characteristics of these sequences to those of the C57BL/6J reference sequence and the recent data sets from the resequencing of 17 inbred strains in the Mouse Genome Project (MGP), and the results unequivocally show that genome introgression from M. m. molossinus into M. m. domesticus provided the primary framework for the mosaic genomes of classical inbred strains. Furthermore, the genomes of C57BL/6J and other classical inbred strains have long consecutive segments with extremely high similarity (>99.998%) to the JF1/Ms strain. In the early 20th century, Japanese waltzing mice with a morphological phenotype resembling that of JF1/Ms mice were often crossed with European fancy mice for early studies of "Mendelism," which suggests that the ancestor of the extant JF1/Ms strain provided the origin of the M. m. molossinus genome in classical inbred strains and largely contributed to its intersubspecific genome diversity.

  12. Global Gene Expression Profiling of Individual Human Oocytes and Embryos Demonstrates Heterogeneity in Early Development

    PubMed Central

    Zeef, Leo; Kimber, Susan J.; Brison, Daniel R.

    2013-01-01

    Early development in humans is characterised by low and variable embryonic viability, reflected in low fecundity and high rates of miscarriage, relative to other mammals. Data from assisted reproduction programmes provides additional evidence that this is largely mediated at the level of embryonic competence and is highly heterogeneous among embryos. Understanding the basis of this heterogeneity has important implications in a number of areas including: the regulation of early human development, disorders of pregnancy, assisted reproduction programmes, the long term health of children which may be programmed in early development, and the molecular basis of pluripotency in human stem cell populations. We have therefore investigated global gene expression profiles using polyAPCR amplification and microarray technology applied to individual human oocytes and 4-cell and blastocyst stage embryos. In order to explore the basis of any variability in detail, each developmental stage is replicated in triplicate. Our data show that although transcript profiles are highly stage-specific, within each stage they are relatively variable. We describe expression of a number of gene families and pathways including apoptosis, cell cycle and amino acid metabolism, which are variably expressed and may be reflective of embryonic developmental competence. Overall, our data suggest that heterogeneity in human embryo developmental competence is reflected in global transcript profiles, and that the vast majority of existing human embryo gene expression data based on pooled oocytes and embryos need to be reinterpreted. PMID:23717564

  13. The dispersed archaeal eukaryome and the complex archaeal ancestor of eukaryotes.

    PubMed

    Koonin, Eugene V; Yutin, Natalya

    2014-04-01

    The ancestral set of eukaryotic genes is a chimera composed of genes of archaeal and bacterial origins thanks to the endosymbiosis event that gave rise to the mitochondria and apparently antedated the last common ancestor of the extant eukaryotes. The proto-mitochondrial endosymbiont is confidently identified as an α-proteobacterium. In contrast, the archaeal ancestor of eukaryotes remains elusive, although evidence is accumulating that it could have belonged to a deep lineage within the TACK (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) superphylum of the Archaea. Recent surveys of archaeal genomes show that the apparent ancestors of several key functional systems of eukaryotes, the components of the archaeal "eukaryome," such as ubiquitin signaling, RNA interference, and actin-based and tubulin-based cytoskeleton structures, are identifiable in different archaeal groups. We suggest that the archaeal ancestor of eukaryotes was a complex form, rooted deeply within the TACK superphylum, that already possessed some quintessential eukaryotic features, in particular, a cytoskeleton, and perhaps was capable of a primitive form of phagocytosis that would facilitate the engulfment of potential symbionts. This putative group of Archaea could have existed for a relatively short time before going extinct or undergoing genome streamlining, resulting in the dispersion of the eukaryome. This scenario might explain the difficulty with the identification of the archaeal ancestor of eukaryotes despite the straightforward detection of apparent ancestors to many signature eukaryotic functional systems.

  14. The Dispersed Archaeal Eukaryome and the Complex Archaeal Ancestor of Eukaryotes

    PubMed Central

    Koonin, Eugene V.; Yutin, Natalya

    2014-01-01

    The ancestral set of eukaryotic genes is a chimera composed of genes of archaeal and bacterial origins thanks to the endosymbiosis event that gave rise to the mitochondria and apparently antedated the last common ancestor of the extant eukaryotes. The proto-mitochondrial endosymbiont is confidently identified as an α-proteobacterium. In contrast, the archaeal ancestor of eukaryotes remains elusive, although evidence is accumulating that it could have belonged to a deep lineage within the TACK (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) superphylum of the Archaea. Recent surveys of archaeal genomes show that the apparent ancestors of several key functional systems of eukaryotes, the components of the archaeal “eukaryome,” such as ubiquitin signaling, RNA interference, and actin-based and tubulin-based cytoskeleton structures, are identifiable in different archaeal groups. We suggest that the archaeal ancestor of eukaryotes was a complex form, rooted deeply within the TACK superphylum, that already possessed some quintessential eukaryotic features, in particular, a cytoskeleton, and perhaps was capable of a primitive form of phagocytosis that would facilitate the engulfment of potential symbionts. This putative group of Archaea could have existed for a relatively short time before going extinct or undergoing genome streamlining, resulting in the dispersion of the eukaryome. This scenario might explain the difficulty with the identification of the archaeal ancestor of eukaryotes despite the straightforward detection of apparent ancestors to many signature eukaryotic functional systems. PMID:24691961

  15. Primary Cortical Folding in the Human Newborn: An Early Marker of Later Functional Development

    ERIC Educational Resources Information Center

    Dubois, J.; Benders, M.; Borradori-Tolsa, C.; Cachia, A.; Lazeyras, F.; Leuchter, R. Ha-Vinh; Sizonenko, S. V.; Warfield, S. K.; Mangin, J. F.; Huppi, P. S.

    2008-01-01

    In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be…

  16. Early Motherhood and Harsh Parenting: The Role of Human, Social, and Cultural Capital

    ERIC Educational Resources Information Center

    Lee, Yookyong

    2009-01-01

    Objective: This study examined the role of maternal human, social, and cultural capital in the relationship between early motherhood and harsh parenting behavior. Methods: This study used data from the Fragile Families and Child Wellbeing (FFCW) Study. Harsh parenting behaviors by mothers who were 19 years or younger at birth of the focal child (n…

  17. Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy.

    PubMed

    Cooke, Gerard M

    2014-01-01

    The first trimester of human fetal life, a period of extremely rapid development of physiological systems, represents the most rapid growth phase in human life. Interference in the establishment of organ systems may result in abnormal development that may be manifest immediately or programmed for later abnormal function. Exposure to environmental chemicals may be affecting development at these early stages, and yet there is limited knowledge of the quantities and identities of the chemicals to which the fetus is exposed during early pregnancy. Clearly, opportunities for assessing fetal chemical exposure directly are extremely limited. Hence, this review describes indirect means of assessing fetal exposure in early pregnancy to chemicals that are considered disrupters of development. Consideration is given to such matrices as maternal hair, fingernails, urine, saliva, sweat, breast milk, amniotic fluid and blood, and fetal matrices such as cord blood, cord tissue, meconium, placenta, and fetal liver. More than 150 articles that presented data from chemical analysis of human maternal and fetal tissues and fluids were reviewed. Priority was given to articles where chemical analysis was conducted in more than one matrix. Where correlations between maternal and fetal matrices were determined, these articles were included and are highlighted, as these may provide the basis for future investigations of early fetal exposure. The determination of fetal chemical exposure, at the time of rapid human growth and development, will greatly assist regulatory agencies in risk assessments and establishment of advisories for risk management concerning environmental chemicals.

  18. HIV epidemiology. The early spread and epidemic ignition of HIV-1 in human populations.

    PubMed

    Faria, Nuno R; Rambaut, Andrew; Suchard, Marc A; Baele, Guy; Bedford, Trevor; Ward, Melissa J; Tatem, Andrew J; Sousa, João D; Arinaminpathy, Nimalan; Pépin, Jacques; Posada, David; Peeters, Martine; Pybus, Oliver G; Lemey, Philippe

    2014-10-01

    Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations.

  19. The early spread and epidemic ignition of HIV-1 in human populations

    PubMed Central

    Faria, Nuno R.; Rambaut, Andrew; Suchard, Marc A.; Baele, Guy; Bedford, Trevor; Ward, Melissa J.; Tatem, Andrew J.; Sousa, João D.; Arinaminpathy, Nimalan; Pépin, Jacques; Posada, David; Peeters, Martine; Pybus, Oliver G.; Lemey, Philippe

    2014-01-01

    Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations. PMID:25278604

  20. The human immediate early gene BRF1 maps to chromosome 14q22-q24

    SciTech Connect

    Maclean, K.N.; Bustin, S.A.; McKay, I.A.; See, C.G.

    1995-11-01

    BRF1 (Butyrate response factor 1) is a member of an immediate early gene family specifying putative nuclear transcription factors. A repeat motif incorporating two Cys and two His is highly conserved between family members identified from yeast, Drosophila, mouse, rat, and human. The chromosome localization of none of the human genes has been determined thus far. Using the polymerase chain reaction on a human-rodent hybrid panel, we have localized BRF1 to chromosome 14. This was confirmed by direct sequencing of the PCR fragment. Using fluorescence in situ hybridization, the chromosome localization of BRF1 was further determined as 14q22-q24. 15 refs., 1 fig.

  1. Early pregnancy factor is an immunosuppressive contaminant of commercial preparations of human chorionic gonadotrophin.

    PubMed Central

    Rolfe, B E; Morton, H; Clarke, F M

    1983-01-01

    Early pregnancy factor (EPF) is a pregnancy associated substance detected in human serum and urine throughout the first and second trimesters of pregnancy. It has also been detected in several commercial preparations of human chorionic gonadotrophin (hCG). The various molecular weight forms of EPF which occur in human pregnancy serum, urine and commercial hCG preparations have been partially characterized and found to be similar to each other but distinct from hCG. Further evidence is presented which suggests that it is EPF rather than hCG which is responsible for the immunosuppressive activity of some crude hCG preparations. PMID:6831771

  2. Synthesis of human adenovirus early RNA species is similar in productive and abortive infections of monkey and human cells.

    PubMed Central

    Anderson, K P; Klessig, D F

    1982-01-01

    Northern (RNA) blot analysis has been used to show that synthesis of early mRNA species is similar in monkey cells productively or abortively infected with human adenovirus. mRNA species from all five major early regions (1A, 1B, 2, 3, 4) are identical in size and comparable in abundance whether isolated from monkey cells infected with adenovirus type 2 or with the host range mutant Ad2hr400 or coinfected with adenovirus type 2 plus simian virus 40. The mRNA species isolated from monkey cells are identical in size to those isolated from human cells. Production of virus-associated RNA is also identical in productive and abortive infections of monkey cells. Synthesis of virus-associated RNA is, however, significantly greater in HeLa cells than in CV1 cells at late times after infection regardless of which virus is used in the infection. Images PMID:6283181

  3. Uptake of Plasmin-PN-1 Complexes in Early Human Atheroma.

    PubMed

    Boukais, Kamel; Bayles, Richard; Borges, Luciano de Figueiredo; Louedec, Liliane; Boulaftali, Yacine; Ho-Tin-Noé, Benoit; Arocas, Véronique; Bouton, Marie-Christine; Michel, Jean-Baptiste

    2016-01-01

    Zymogens are delivered to the arterial wall by radial transmural convection. Plasminogen can be activated within the arterial wall to produce plasmin, which is involved in evolution of the atherosclerotic plaque. Vascular smooth muscle cells (vSMCs) protect the vessels from proteolytic injury due to atherosclerosis development by highly expressing endocytic LDL receptor-related protein-1 (LRP-1), and by producing anti-proteases, such as Protease Nexin-1 (PN-1). PN-1 is able to form covalent complexes with plasmin. We hypothesized that plasmin-PN-1 complexes could be internalized via LRP-1 by vSMCs during the early stages of human atheroma. LRP-1 is also responsible for the capture of aggregated LDL in human atheroma. Plasmin activity and immunohistochemical analyses of early human atheroma showed that the plasminergic system is activated within the arterial wall, where intimal foam cells, including vSMCs and platelets, are the major sites of PN-1 accumulation. Both PN-1 and LRP-1 are overexpressed in early atheroma at both messenger and protein levels. Cell biology studies demonstrated an increased expression of PN-1 and tissue plasminogen activator by vSMCs in response to LDL. Plasmin-PN-1 complexes are internalized via LRP-1 in vSMCs, whereas plasmin alone is not. Tissue PN-1 interacts with plasmin in early human atheroma via two complementary mechanisms: plasmin inhibition and tissue uptake of plasmin-PN-1 complexes via LRP-1 in vSMCs. Despite this potential protective effect, plasminogen activation by vSMCs remains abnormally elevated in the intima in early stages of human atheroma.

  4. Uptake of Plasmin-PN-1 Complexes in Early Human Atheroma

    PubMed Central

    Boukais, Kamel; Bayles, Richard; Borges, Luciano de Figueiredo; Louedec, Liliane; Boulaftali, Yacine; Ho-Tin-Noé, Benoit; Arocas, Véronique; Bouton, Marie-Christine; Michel, Jean-Baptiste

    2016-01-01

    Zymogens are delivered to the arterial wall by radial transmural convection. Plasminogen can be activated within the arterial wall to produce plasmin, which is involved in evolution of the atherosclerotic plaque. Vascular smooth muscle cells (vSMCs) protect the vessels from proteolytic injury due to atherosclerosis development by highly expressing endocytic LDL receptor-related protein-1 (LRP-1), and by producing anti-proteases, such as Protease Nexin-1 (PN-1). PN-1 is able to form covalent complexes with plasmin. We hypothesized that plasmin-PN-1 complexes could be internalized via LRP-1 by vSMCs during the early stages of human atheroma. LRP-1 is also responsible for the capture of aggregated LDL in human atheroma. Plasmin activity and immunohistochemical analyses of early human atheroma showed that the plasminergic system is activated within the arterial wall, where intimal foam cells, including vSMCs and platelets, are the major sites of PN-1 accumulation. Both PN-1 and LRP-1 are overexpressed in early atheroma at both messenger and protein levels. Cell biology studies demonstrated an increased expression of PN-1 and tissue plasminogen activator by vSMCs in response to LDL. Plasmin-PN-1 complexes are internalized via LRP-1 in vSMCs, whereas plasmin alone is not. Tissue PN-1 interacts with plasmin in early human atheroma via two complementary mechanisms: plasmin inhibition and tissue uptake of plasmin-PN-1 complexes via LRP-1 in vSMCs. Despite this potential protective effect, plasminogen activation by vSMCs remains abnormally elevated in the intima in early stages of human atheroma. PMID:27445860

  5. Uptake of Plasmin-PN-1 Complexes in Early Human Atheroma.

    PubMed

    Boukais, Kamel; Bayles, Richard; Borges, Luciano de Figueiredo; Louedec, Liliane; Boulaftali, Yacine; Ho-Tin-Noé, Benoit; Arocas, Véronique; Bouton, Marie-Christine; Michel, Jean-Baptiste

    2016-01-01

    Zymogens are delivered to the arterial wall by radial transmural convection. Plasminogen can be activated within the arterial wall to produce plasmin, which is involved in evolution of the atherosclerotic plaque. Vascular smooth muscle cells (vSMCs) protect the vessels from proteolytic injury due to atherosclerosis development by highly expressing endocytic LDL receptor-related protein-1 (LRP-1), and by producing anti-proteases, such as Protease Nexin-1 (PN-1). PN-1 is able to form covalent complexes with plasmin. We hypothesized that plasmin-PN-1 complexes could be internalized via LRP-1 by vSMCs during the early stages of human atheroma. LRP-1 is also responsible for the capture of aggregated LDL in human atheroma. Plasmin activity and immunohistochemical analyses of early human atheroma showed that the plasminergic system is activated within the arterial wall, where intimal foam cells, including vSMCs and platelets, are the major sites of PN-1 accumulation. Both PN-1 and LRP-1 are overexpressed in early atheroma at both messenger and protein levels. Cell biology studies demonstrated an increased expression of PN-1 and tissue plasminogen activator by vSMCs in response to LDL. Plasmin-PN-1 complexes are internalized via LRP-1 in vSMCs, whereas plasmin alone is not. Tissue PN-1 interacts with plasmin in early human atheroma via two complementary mechanisms: plasmin inhibition and tissue uptake of plasmin-PN-1 complexes via LRP-1 in vSMCs. Despite this potential protective effect, plasminogen activation by vSMCs remains abnormally elevated in the intima in early stages of human atheroma. PMID:27445860

  6. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    SciTech Connect

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-12-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection.

  7. Early Pleistocene third metacarpal from Kenya and the evolution of modern human-like hand morphology.

    PubMed

    Ward, Carol V; Tocheri, Matthew W; Plavcan, J Michael; Brown, Francis H; Manthi, Fredrick Kyalo

    2014-01-01

    Despite discoveries of relatively complete hands from two early hominin species (Ardipithecus ramidus and Australopithecus sediba) and partial hands from another (Australopithecus afarensis), fundamental questions remain about the evolution of human-like hand anatomy and function. These questions are driven by the paucity of hand fossils in the hominin fossil record between 800,000 and 1.8 My old, a time interval well documented for the emergence and subsequent proliferation of Acheulian technology (shaped bifacial stone tools). Modern and Middle to Late Pleistocene humans share a suite of derived features in the thumb, wrist, and radial carpometacarpal joints that is noticeably absent in early hominins. Here we show that one of the most distinctive features of this suite in the Middle Pleistocene to recent human hand, the third metacarpal styloid process, was present ∼1.42 Mya in an East African hominin from Kaitio, West Turkana, Kenya. This fossil thus provides the earliest unambiguous evidence for the evolution of a key shared derived characteristic of modern human and Neandertal hand morphology and suggests that the distinctive complex of radial carpometacarpal joint features in the human hand arose early in the evolution of the genus Homo and probably in Homo erectus sensu lato. PMID:24344276

  8. Early Pleistocene third metacarpal from Kenya and the evolution of modern human-like hand morphology.

    PubMed

    Ward, Carol V; Tocheri, Matthew W; Plavcan, J Michael; Brown, Francis H; Manthi, Fredrick Kyalo

    2014-01-01

    Despite discoveries of relatively complete hands from two early hominin species (Ardipithecus ramidus and Australopithecus sediba) and partial hands from another (Australopithecus afarensis), fundamental questions remain about the evolution of human-like hand anatomy and function. These questions are driven by the paucity of hand fossils in the hominin fossil record between 800,000 and 1.8 My old, a time interval well documented for the emergence and subsequent proliferation of Acheulian technology (shaped bifacial stone tools). Modern and Middle to Late Pleistocene humans share a suite of derived features in the thumb, wrist, and radial carpometacarpal joints that is noticeably absent in early hominins. Here we show that one of the most distinctive features of this suite in the Middle Pleistocene to recent human hand, the third metacarpal styloid process, was present ∼1.42 Mya in an East African hominin from Kaitio, West Turkana, Kenya. This fossil thus provides the earliest unambiguous evidence for the evolution of a key shared derived characteristic of modern human and Neandertal hand morphology and suggests that the distinctive complex of radial carpometacarpal joint features in the human hand arose early in the evolution of the genus Homo and probably in Homo erectus sensu lato.

  9. Early Pleistocene third metacarpal from Kenya and the evolution of modern human-like hand morphology

    PubMed Central

    Ward, Carol V.; Tocheri, Matthew W.; Plavcan, J. Michael; Brown, Francis H.; Manthi, Fredrick Kyalo

    2014-01-01

    Despite discoveries of relatively complete hands from two early hominin species (Ardipithecus ramidus and Australopithecus sediba) and partial hands from another (Australopithecus afarensis), fundamental questions remain about the evolution of human-like hand anatomy and function. These questions are driven by the paucity of hand fossils in the hominin fossil record between 800,000 and 1.8 My old, a time interval well documented for the emergence and subsequent proliferation of Acheulian technology (shaped bifacial stone tools). Modern and Middle to Late Pleistocene humans share a suite of derived features in the thumb, wrist, and radial carpometacarpal joints that is noticeably absent in early hominins. Here we show that one of the most distinctive features of this suite in the Middle Pleistocene to recent human hand, the third metacarpal styloid process, was present ∼1.42 Mya in an East African hominin from Kaitio, West Turkana, Kenya. This fossil thus provides the earliest unambiguous evidence for the evolution of a key shared derived characteristic of modern human and Neandertal hand morphology and suggests that the distinctive complex of radial carpometacarpal joint features in the human hand arose early in the evolution of the genus Homo and probably in Homo erectus sensu lato. PMID:24344276

  10. Human Y chromosome haplogroup R-V88: a paternal genetic record of early mid Holocene trans-Saharan connections and the spread of Chadic languages

    PubMed Central

    Cruciani, Fulvio; Trombetta, Beniamino; Sellitto, Daniele; Massaia, Andrea; Destro-Bisol, Giovanni; Watson, Elizabeth; Beraud Colomb, Eliane; Dugoujon, Jean-Michel; Moral, Pedro; Scozzari, Rosaria

    2010-01-01

    Although human Y chromosomes belonging to haplogroup R1b are quite rare in Africa, being found mainly in Asia and Europe, a group of chromosomes within the paragroup R-P25* are found concentrated in the central-western part of the African continent, where they can be detected at frequencies as high as 95%. Phylogenetic evidence and coalescence time estimates suggest that R-P25* chromosomes (or their phylogenetic ancestor) may have been carried to Africa by an Asia-to-Africa back migration in prehistoric times. Here, we describe six new mutations that define the relationships among the African R-P25* Y chromosomes and between these African chromosomes and earlier reported R-P25 Eurasian sub-lineages. The incorporation of these new mutations into a phylogeny of the R1b haplogroup led to the identification of a new clade (R1b1a or R-V88) encompassing all the African R-P25* and about half of the few European/west Asian R-P25* chromosomes. A worldwide phylogeographic analysis of the R1b haplogroup provided strong support to the Asia-to-Africa back-migration hypothesis. The analysis of the distribution of the R-V88 haplogroup in >1800 males from 69 African populations revealed a striking genetic contiguity between the Chadic-speaking peoples from the central Sahel and several other Afroasiatic-speaking groups from North Africa. The R-V88 coalescence time was estimated at 9200–5600 kya, in the early mid Holocene. We suggest that R-V88 is a paternal genetic record of the proposed mid-Holocene migration of proto-Chadic Afroasiatic speakers through the Central Sahara into the Lake Chad Basin, and geomorphological evidence is consistent with this view. PMID:20051990

  11. Digital Literacy Practices and Pedagogical Moments: Human and Non-Human Intertwining in Early Childhood Education

    ERIC Educational Resources Information Center

    Lafton, Tove

    2015-01-01

    Various forms of digital devices have established themselves as resources within constructions of professional practices in early childhood education. This article is centred on the question of how we might rethink an example of digital practice based on a Foucauldian understanding of discourse and a rhizomatic understanding of digital practice…

  12. IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy

    PubMed Central

    Millar, Neal L.; Akbar, Moeed; Campbell, Abigail L.; Reilly, James H.; Kerr, Shauna C.; McLean, Michael; Frleta-Gilchrist, Marina; Fazzi, Umberto G.; Leach, William J.; Rooney, Brian P.; Crowe, Lindsay A. N.; Murrell, George A. C.; McInnes, Iain B.

    2016-01-01

    Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence of interleukin 17A (IL-17A) expression in early human tendinopathy and thereafter, explored mechanisms whereby IL-17A mediated inflammation and tissue remodeling in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) along with control biopsies were collected from patients undergoing shoulder surgery. Markers of inflammation and IL-17A were quantified by RT-PCR and immunohistochemistry. Human tendon cells were derived from hamstring tendon obtained during ACL reconstruction. In vitro effects of IL-17A upon tenocytes were measured using RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of IL-17A was detected in ‘early tendinopathy’ compared to both matched samples and non-matched control samples (p < 0.01) by RT-PCR and immunostaining. Double immunofluoresence staining revealed IL-17A expression in leukocyte subsets including mast cells, macrophages and T cells. IL-17A treated tenocytes exhibited increased production of proinflammatory cytokines (p < 0.001), altered matrix regulation (p < 0.01) with increased Collagen type III and increased expression of several apoptosis related factors. We propose IL-17A as an inflammatory mediator within the early tendinopathy processes thus providing novel therapeutic approaches in the management of tendon disorders. PMID:27263531

  13. Starch grains on human teeth reveal early broad crop diet in northern Peru

    PubMed Central

    Piperno, Dolores R.; Dillehay, Tom D.

    2008-01-01

    Previous research indicates that the Ñanchoc Valley in northern Peru was an important locus of early and middle Holocene human settlement, and that between 9200 and 5500 14C yr B.P. the valley inhabitants adopted major crop plants such as squash (Cucurbita moschata), peanuts (Arachis sp.), and cotton (Gossypium barbadense). We report here an examination of starch grains preserved in the calculus of human teeth from these sites that provides direct evidence for the early consumption of cultivated squash and peanuts along with two other major food plants not previously detected. Starch from the seeds of Phaseolus and Inga feuillei, the flesh of Cucurbita moschata fruits, and the nuts of Arachis was routinely present on numerous teeth that date to between 8210 and 6970 14C yr B.P. Early plant diets appear to have been diverse and stable through time and were rich in cultivated foods typical of later Andean agriculture. Our data provide early archaeological evidence for Phaseolus beans and I. feuillei, an important tree crop, and indicate that effective food production systems that contributed significant dietary inputs were present in the Ñanchoc region by 8000 14C yr B.P. Starch grain studies of dental remains document plants and edible parts of them not normally preserved in archaeological records and can assume primary roles as direct indicators of ancient human diets and agriculture. PMID:19066222

  14. IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy.

    PubMed

    Millar, Neal L; Akbar, Moeed; Campbell, Abigail L; Reilly, James H; Kerr, Shauna C; McLean, Michael; Frleta-Gilchrist, Marina; Fazzi, Umberto G; Leach, William J; Rooney, Brian P; Crowe, Lindsay A N; Murrell, George A C; McInnes, Iain B

    2016-01-01

    Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence of interleukin 17A (IL-17A) expression in early human tendinopathy and thereafter, explored mechanisms whereby IL-17A mediated inflammation and tissue remodeling in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') along with control biopsies were collected from patients undergoing shoulder surgery. Markers of inflammation and IL-17A were quantified by RT-PCR and immunohistochemistry. Human tendon cells were derived from hamstring tendon obtained during ACL reconstruction. In vitro effects of IL-17A upon tenocytes were measured using RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of IL-17A was detected in 'early tendinopathy' compared to both matched samples and non-matched control samples (p < 0.01) by RT-PCR and immunostaining. Double immunofluoresence staining revealed IL-17A expression in leukocyte subsets including mast cells, macrophages and T cells. IL-17A treated tenocytes exhibited increased production of proinflammatory cytokines (p < 0.001), altered matrix regulation (p < 0.01) with increased Collagen type III and increased expression of several apoptosis related factors. We propose IL-17A as an inflammatory mediator within the early tendinopathy processes thus providing novel therapeutic approaches in the management of tendon disorders. PMID:27263531

  15. A molecular palaeobiological hypothesis for the origin of aplacophoran molluscs and their derivation from chiton-like ancestors

    PubMed Central

    Vinther, Jakob; Sperling, Erik A.; Briggs, Derek E. G.; Peterson, Kevin J.

    2012-01-01

    Aplacophorans have long been argued to be basal molluscs. We present a molecular phylogeny, including the aplacophorans Neomeniomorpha (Solenogastres) and Chaetodermomorpha (Caudofoveata), which recovered instead the clade Aculifera (Aplacophora + Polyplacophora). Our relaxed Bayesian molecular clock estimates an Early Ordovician appearance of the aculiferan crown group consistent with the presence of chiton-like molluscs with seven or eight dorsal shell plates by the Late Cambrian (approx. 501–490 Ma). Molecular, embryological and palaeontological data indicate that aplacophorans, as well as chitons, evolved from a paraphyletic assemblage of chiton-like ancestors. The recovery of cephalopods as a sister group to aculiferans suggests that the plesiomorphic condition in molluscs might be a morphology similar to that found in monoplacophorans. PMID:21976685

  16. A molecular palaeobiological hypothesis for the origin of aplacophoran molluscs and their derivation from chiton-like ancestors.

    PubMed

    Vinther, Jakob; Sperling, Erik A; Briggs, Derek E G; Peterson, Kevin J

    2012-04-01

    Aplacophorans have long been argued to be basal molluscs. We present a molecular phylogeny, including the aplacophorans Neomeniomorpha (Solenogastres) and Chaetodermomorpha (Caudofoveata), which recovered instead the clade Aculifera (Aplacophora + Polyplacophora). Our relaxed Bayesian molecular clock estimates an Early Ordovician appearance of the aculiferan crown group consistent with the presence of chiton-like molluscs with seven or eight dorsal shell plates by the Late Cambrian (approx. 501-490 Ma). Molecular, embryological and palaeontological data indicate that aplacophorans, as well as chitons, evolved from a paraphyletic assemblage of chiton-like ancestors. The recovery of cephalopods as a sister group to aculiferans suggests that the plesiomorphic condition in molluscs might be a morphology similar to that found in monoplacophorans.

  17. A molecular palaeobiological hypothesis for the origin of aplacophoran molluscs and their derivation from chiton-like ancestors.

    PubMed

    Vinther, Jakob; Sperling, Erik A; Briggs, Derek E G; Peterson, Kevin J

    2012-04-01

    Aplacophorans have long been argued to be basal molluscs. We present a molecular phylogeny, including the aplacophorans Neomeniomorpha (Solenogastres) and Chaetodermomorpha (Caudofoveata), which recovered instead the clade Aculifera (Aplacophora + Polyplacophora). Our relaxed Bayesian molecular clock estimates an Early Ordovician appearance of the aculiferan crown group consistent with the presence of chiton-like molluscs with seven or eight dorsal shell plates by the Late Cambrian (approx. 501-490 Ma). Molecular, embryological and palaeontological data indicate that aplacophorans, as well as chitons, evolved from a paraphyletic assemblage of chiton-like ancestors. The recovery of cephalopods as a sister group to aculiferans suggests that the plesiomorphic condition in molluscs might be a morphology similar to that found in monoplacophorans. PMID:21976685

  18. The eukaryotic ancestor had a complex ubiquitin signaling system of archaeal origin.

    PubMed

    Grau-Bové, Xavier; Sebé-Pedrós, Arnau; Ruiz-Trillo, Iñaki

    2015-03-01

    The origin of the eukaryotic cell is one of the most important transitions in the history of life. However, the emergence and early evolution of eukaryotes remains poorly understood. Recent data have shown that the last eukaryotic common ancestor (LECA) was much more complex than previously thought. The LECA already had the genetic machinery encoding the endomembrane apparatus, spliceosome, nuclear pore, and myosin and kinesin cytoskeletal motors. It is unclear, however, when the functional regulation of these cellular components evolved. Here, we address this question by analyzing the origin and evolution of the ubiquitin (Ub) signaling system, one of the most important regulatory layers in eukaryotes. We delineated the evolution of the whole Ub, Small-Ub-related MOdifier (SUMO), and Ub-fold modifier 1 (Ufm1) signaling networks by analyzing representatives from all major eukaryotic, bacterial, and archaeal lineages. We found that the Ub toolkit had a pre-eukaryotic origin and is present in three extant archaeal groups. The pre-eukaryotic Ub toolkit greatly expanded during eukaryogenesis, through massive gene innovation and diversification of protein domain architectures. This resulted in a LECA with essentially all of the Ub-related genes, including the SUMO and Ufm1 Ub-like systems. Ub and SUMO signaling further expanded during eukaryotic evolution, especially labeling and delabeling enzymes responsible for substrate selection. Additionally, we analyzed protein domain architecture evolution and found that multicellular lineages have the most complex Ub systems in terms of domain architectures. Together, we demonstrate that the Ub system predates the origin of eukaryotes and that a burst of innovation during eukaryogenesis led to a LECA with complex posttranslational regulation.

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

    PubMed

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

    2011-05-22

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

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

    PubMed Central

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

    2013-01-01

    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

  1. A Re-Appraisal of the Early Andean Human Remains from Lauricocha in Peru.

    PubMed

    Fehren-Schmitz, Lars; Llamas, Bastien; Lindauer, Susanne; Tomasto-Cagigao, Elsa; Kuzminsky, Susan; Rohland, Nadin; Santos, Fabrício R; Kaulicke, Peter; Valverde, Guido; Richards, Stephen M; Nordenfelt, Susanne; Seidenberg, Verena; Mallick, Swapan; Cooper, Alan; Reich, David; Haak, Wolfgang

    2015-01-01

    The discovery of human remains from the Lauricocha cave in the Central Andean highlands in the 1960's provided the first direct evidence for human presence in the high altitude Andes. The skeletons found at this site were ascribed to the Early to Middle Holocene and represented the oldest known population of Western South America, and thus were used in several studies addressing the early population history of the continent. However, later excavations at Lauricocha led to doubts regarding the antiquity of the site. Here, we provide new dating, craniometric, and genetic evidence for this iconic site. We obtained new radiocarbon dates, generated complete mitochondrial genomes and nuclear SNP data from five individuals, and re-analyzed the human remains of Lauricocha to revise the initial morphological and craniometric analysis conducted in the 1960's. We show that Lauricocha was indeed occupied in the Early to Middle Holocene but the temporal spread of dates we obtained from the human remains show that they do not qualify as a single contemporaneous population. However, the genetic results from five of the individuals fall within the spectrum of genetic diversity observed in pre-Columbian and modern Native Central American populations.

  2. A Re-Appraisal of the Early Andean Human Remains from Lauricocha in Peru

    PubMed Central

    Kuzminsky, Susan; Rohland, Nadin; Santos, Fabrício R.; Kaulicke, Peter; Valverde, Guido; Richards, Stephen M.; Nordenfelt, Susanne; Seidenberg, Verena; Mallick, Swapan; Cooper, Alan; Reich, David; Haak, Wolfgang

    2015-01-01

    The discovery of human remains from the Lauricocha cave in the Central Andean highlands in the 1960’s provided the first direct evidence for human presence in the high altitude Andes. The skeletons found at this site were ascribed to the Early to Middle Holocene and represented the oldest known population of Western South America, and thus were used in several studies addressing the early population history of the continent. However, later excavations at Lauricocha led to doubts regarding the antiquity of the site. Here, we provide new dating, craniometric, and genetic evidence for this iconic site. We obtained new radiocarbon dates, generated complete mitochondrial genomes and nuclear SNP data from five individuals, and re-analyzed the human remains of Lauricocha to revise the initial morphological and craniometric analysis conducted in the 1960’s. We show that Lauricocha was indeed occupied in the Early to Middle Holocene but the temporal spread of dates we obtained from the human remains show that they do not qualify as a single contemporaneous population. However, the genetic results from five of the individuals fall within the spectrum of genetic diversity observed in pre-Columbian and modern Native Central American populations. PMID:26061688

  3. Early and Late Damages in Chromosome 3 of Human Lymphocytes After Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Sunagawa, Mayumi; Mangala, Lingegowda; Zhang, Ye; Kahdim, Munira; Wilson, Bobby; Cucinotta, Francis A.; Wu, Honglu

    2011-01-01

    Tumor formation in humans or animals is a multi-step process. An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. GI is defined as elevated or persistent genetic damages occurring many generations after the cells are exposed. While early studies have demonstrated radiation-induced GI in several cell types as detected in endpoints such as mutation, apoptosis and damages in chromosomes, the dependence of GI on the quality of radiation remains uncertain. To investigate GI in human lymphocytes induced by both low- and high-LET radiation, we initially exposed white blood cells collected from healthy subjects to gamma rays in vitro, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis post irradiation and at several intervals during the culture period. Among a number of biological endpoints planned for the project, the multi-color banding fluorescent in situ hybridization (mBAND) allows identification of inversions that were expected to be stable. We present here early and late chromosome aberrations detected with mBAND in chromosome 3 after gamma exposure. Comparison of chromosome damages in between human lymphocytes and human epithelial cells is also discussed

  4. Size and power required for motion with implication for the evolution of early hominids.

    PubMed

    Wang, W J; Crompton, R H

    2003-09-01

    The fossil record of early hominids (early human ancestors) suggests that their stature and weight had a tendency to increase, but their robusticity (the proportion of radius to length) to decrease. Using a simple musculo-skeletal model, this paper explores possible relationships between size, power required for motion (PRM) and cycle-time, deriving relationships which indicate that PRM per unit of mass and velocity is proportional to robusticity, but inversely proportional to stature. The results derived appear to be in general agreement with published data from physiological experiments. If the material properties of early hominids were similar to those of modern humans and the achievement of minimum PRM was the selective criterion, human stature might tend to increase slightly in human evolution (and, if selective pressures are not removed, might do so in the future but at lower rate). If mobility and stability under loading are the selective criteria, however, human size should not substantially increase in the future.

  5. Molecular paleontology and complexity in the last eukaryotic common ancestor.

    PubMed

    Koumandou, V Lila; Wickstead, Bill; Ginger, Michael L; van der Giezen, Mark; Dacks, Joel B; Field, Mark C

    2013-01-01

    Eukaryogenesis, the origin of the eukaryotic cell, represents one of the fundamental evolutionary transitions in the history of life on earth. This event, which is estimated to have occurred over one billion years ago, remains rather poorly understood. While some well-validated examples of fossil microbial eukaryotes for this time frame have been described, these can provide only basic morphology and the molecular machinery present in these organisms has remained unknown. Complete and partial genomic information has begun to fill this gap, and is being used to trace proteins and cellular traits to their roots and to provide unprecedented levels of resolution of structures, metabolic pathways and capabilities of organisms at these earliest points within the eukaryotic lineage. This is essentially allowing a molecular paleontology. What has emerged from these studies is spectacular cellular complexity prior to expansion of the eukaryotic lineages. Multiple reconstructed cellular systems indicate a very sophisticated biology, which by implication arose following the initial eukaryogenesis event but prior to eukaryotic radiation and provides a challenge in terms of explaining how these early eukaryotes arose and in understanding how they lived. Here, we provide brief overviews of several cellular systems and the major emerging conclusions, together with predictions for subsequent directions in evolution leading to extant taxa. We also consider what these reconstructions suggest about the life styles and capabilities of these earliest eukaryotes and the period of evolution between the radiation of eukaryotes and the eukaryogenesis event itself.

  6. Molecular paleontology and complexity in the last eukaryotic common ancestor

    PubMed Central

    Koumandou, V. Lila; Wickstead, Bill; Ginger, Michael L.; van der Giezen, Mark; Dacks, Joel B.

    2013-01-01

    Eukaryogenesis, the origin of the eukaryotic cell, represents one of the fundamental evolutionary transitions in the history of life on earth. This event, which is estimated to have occurred over one billion years ago, remains rather poorly understood. While some well-validated examples of fossil microbial eukaryotes for this time frame have been described, these can provide only basic morphology and the molecular machinery present in these organisms has remained unknown. Complete and partial genomic information has begun to fill this gap, and is being used to trace proteins and cellular traits to their roots and to provide unprecedented levels of resolution of structures, metabolic pathways and capabilities of organisms at these earliest points within the eukaryotic lineage. This is essentially allowing a molecular paleontology. What has emerged from these studies is spectacular cellular complexity prior to expansion of the eukaryotic lineages. Multiple reconstructed cellular systems indicate a very sophisticated biology, which by implication arose following the initial eukaryogenesis event but prior to eukaryotic radiation and provides a challenge in terms of explaining how these early eukaryotes arose and in understanding how they lived. Here, we provide brief overviews of several cellular systems and the major emerging conclusions, together with predictions for subsequent directions in evolution leading to extant taxa. We also consider what these reconstructions suggest about the life styles and capabilities of these earliest eukaryotes and the period of evolution between the radiation of eukaryotes and the eukaryogenesis event itself. PMID:23895660

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

    PubMed

    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

    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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    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

    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.

  10. [On the road to a new humanity: the reception of psychoanalysis in the early Kinderladen movement].

    PubMed

    Kauders, Anthony D

    2014-01-01

    In the late 1960s a group of students in West Germany founded the so-called Kinderläden (day care centers) in order to experiment with new forms of early childhood education. Members of the early Kinderladen movement in particular pursued a radically utopian approach that, they hoped, would engender new human beings. With the aid of psychoanalytic writings, especially those of Wilhelm Reich, they sought to create subjects that would overcome repressive bourgeois norms and live out their sexuality freely. This reliance on Reich entailed a new interpretation of the "base", as psychoanalytic drive theory supplanted Marxist theory. As such, the early Kinderladen ac- tivists regarded the "basis" of society in biological, psychological, and pedagogic rather than economic terms.

  11. [On the road to a new humanity: the reception of psychoanalysis in the early Kinderladen movement].

    PubMed

    Kauders, Anthony D

    2014-01-01

    In the late 1960s a group of students in West Germany founded the so-called Kinderläden (day care centers) in order to experiment with new forms of early childhood education. Members of the early Kinderladen movement in particular pursued a radically utopian approach that, they hoped, would engender new human beings. With the aid of psychoanalytic writings, especially those of Wilhelm Reich, they sought to create subjects that would overcome repressive bourgeois norms and live out their sexuality freely. This reliance on Reich entailed a new interpretation of the "base", as psychoanalytic drive theory supplanted Marxist theory. As such, the early Kinderladen ac- tivists regarded the "basis" of society in biological, psychological, and pedagogic rather than economic terms. PMID:25872313

  12. Evidence for declines in human population densities during the early Upper Paleolithic in western Europe

    PubMed Central

    Morin, Eugène

    2008-01-01

    In western Europe, the Middle to Upper Paleolithic (M/UP) transition, dated between ≈35,000 and ≈40,000 radiocarbon years, corresponded to a period of major human biological and cultural changes. However, information on human population densities is scarce for that period. New faunal data from the high-resolution record of Saint-Césaire, France, indicate an episode of significant climatic deterioration during the early Upper Paleolithic (EUP), which also was associated with a reduction in mammalian species diversity. High correlations between ethnographic data and mammalian species diversity suggest that this shift decreased human population densities. Reliance on reindeer (Rangifer tarandus), a highly fluctuating resource, would also have promoted declines in human population densities. These data suggest that the EUP represented for humans a period of significant niche contraction in western Europe. In this context, the possibility that a modern human expansion occurred in this region seems low. Instead, it is suggested that population bottlenecks, genetic drift, and gene flow prevailed over human population replacement as mechanisms of evolution in humans during the EUP. PMID:18172204

  13. Transcriptional Factor PU.1 Regulates Decidual C1q Expression in Early Pregnancy in Human.

    PubMed

    Madhukaran, Shanmuga Priyaa; Kishore, Uday; Jamil, Kaiser; Teo, Boon Heng Dennis; Choolani, Mahesh; Lu, Jinhua

    2015-01-01

    C1q is the first recognition subcomponent of the complement classical pathway, which in addition to being synthesized in the liver, is also expressed by macrophages and dendritic cells (DCs). Trophoblast invasion during early placentation results in accumulation of debris that triggers the complement system. Hence, both early and late components of the classical pathway are widely distributed in the placenta and decidua. In addition, C1q has recently been shown to significantly contribute to feto-maternal tolerance, trophoblast migration, and spiral artery remodeling, although the exact mechanism remains unknown. Pregnancy in mice, genetically deficient in C1q, mirrors symptoms similar to that of human preeclampsia. Thus, regulated complement activation has been proposed as an essential requirement for normal successful pregnancy. Little is known about the molecular pathways that regulate C1q expression in pregnancy. PU.1, an Ets-family transcription factor, is required for the development of hematopoietic myeloid lineage immune cells, and its expression is tissue-specific. Recently, PU.1 has been shown to regulate C1q gene expression in DCs and macrophages. Here, we have examined if PU.1 transcription factor regulates decidual C1q expression. We used immune-histochemical analysis, PCR, and immunostaining to localize and study the gene expression of PU.1 transcription factor in early human decidua. PU.1 was highly expressed at gene and protein level in early human decidual cells including trophoblast and stromal cells. Surprisingly, nuclear as well as cytoplasmic PU.1 expression was observed. Decidual cells with predominantly nuclear PU.1 expression had higher C1q expression. It is likely that nuclear and cytoplasmic PU.1 localization has a role to play in early pregnancy via regulating C1q expression in the decidua during implantation.

  14. Expression of immediate early genes after treatment of human astrocytoma cells with radiation and taxol

    SciTech Connect

    Gubits, R.M.; Geard, C.R.; Schiff, P.B.

    1993-10-20

    The promising chemotherapeutic agent, taxol, has been shown to sensitize the G18 line of human astrocytoma cells to ionizing radiation. The present studies were performed to identify specific changes in gene expression associated with this altered sensitivity. The products of immediate early genes, which are induced transiently in cells in response to a variety of treatments, including growth factors, neurotransmitters, and irradiation with UV light or X rays, are thought to initiate a cascade of genetic responses to alterations in cellular environment. The present results demonstrate a dramatic attenuation in one immediate early gene response in association with a treatment that enhances radiosensitivity in a refractory human brain tumor line. 22 refs., 5 figs., 1 tab.

  15. Expression of opsin genes early in ocular development of humans and mice.

    PubMed

    Tarttelin, Emma E; Bellingham, James; Bibb, Lindsay C; Foster, Russell G; Hankins, Mark W; Gregory-Evans, Kevin; Gregory-Evans, Cheryl Y; Wells, Dominic J; Lucas, Robert J

    2003-03-01

    We have compared the onsets of expression of the classical visual opsins with those of the non-rod, non-cone opsins in foetal and post-natal eye tissue from mice and humans. Mouse Rgr-opsin, peropsin, encephalopsin and melanopsin are all expressed in foetal development by E11.5, unlike the murine rod and cone opsins that exhibit post-natal expression, e.g. P1 for ultraviolet cone opsin and P5 for rod opsin. Human non-rod, non-cone opsins are also all expressed early, by 8.6 weeks post-conception. The implications of these observations are discussed with regard to the possible functions of these opsins at early stages of ocular development.

  16. Vertebral numbers and human evolution.

    PubMed

    Williams, Scott A; Middleton, Emily R; Villamil, Catalina I; Shattuck, Milena R

    2016-01-01

    Ever since Tyson (1699), anatomists have noted and compared differences in the regional numbers of vertebrae among humans and other hominoids. Subsequent workers interpreted these differences in phylogenetic, functional, and behavioral frameworks and speculated on the history of vertebral numbers during human evolution. Even in a modern phylogenetic framework and with greatly expanded sample sizes of hominoid species, researchers' conclusions vary drastically, positing that hominins evolved from either a "long-backed" (numerically long lumbar column) or a "short-backed" (numerically short lumbar column) ancestor. We show that these disparate interpretations are due in part to the use of different criteria for what defines a lumbar vertebra, but argue that, regardless of which lumbar definition is used, hominins are similar to their great ape relatives in possessing a short trunk, a rare occurrence in mammals and one that defines the clade Hominoidea. Furthermore, we address the recent claim that the early hominin thoracolumbar configuration is not distinct from that of modern humans and conclude that early hominins show evidence of "cranial shifting," which might explain the anomalous morphology of several early hominin fossils. Finally, we evaluate the competing hypotheses on numbers of vertebrae and argue that the current data support a hominin ancestor with an African ape-like short trunk and lower back.

  17. Early Upper Paleolithic in Eastern Europe and implications for the dispersal of modern humans.

    PubMed

    Anikovich, M V; Sinitsyn, A A; Hoffecker, John F; Holliday, Vance T; Popov, V V; Lisitsyn, S N; Forman, Steven L; Levkovskaya, G M; Pospelova, G A; Kuz'mina, I E; Burova, N D; Goldberg, Paul; Macphail, Richard I; Giaccio, Biagio; Praslov, N D

    2007-01-12

    Radiocarbon and optically stimulated luminescence dating and magnetic stratigraphy indicate Upper Paleolithic occupation-probably representing modern humans-at archaeological sites on the Don River in Russia 45,000 to 42,000 years ago. The oldest levels at Kostenki underlie a volcanic ash horizon identified as the Campanian Ignimbrite Y5 tephra that is dated elsewhere to about 40,000 years ago. The occupation layers contain bone and ivory artifacts, including possible figurative art, and fossil shells imported more than 500 kilometers. Thus, modern humans appeared on the central plain of Eastern Europe as early as anywhere else in northern Eurasia. PMID:17218523

  18. Early Upper Paleolithic in Eastern Europe and implications for the dispersal of modern humans.

    PubMed

    Anikovich, M V; Sinitsyn, A A; Hoffecker, John F; Holliday, Vance T; Popov, V V; Lisitsyn, S N; Forman, Steven L; Levkovskaya, G M; Pospelova, G A; Kuz'mina, I E; Burova, N D; Goldberg, Paul; Macphail, Richard I; Giaccio, Biagio; Praslov, N D

    2007-01-12

    Radiocarbon and optically stimulated luminescence dating and magnetic stratigraphy indicate Upper Paleolithic occupation-probably representing modern humans-at archaeological sites on the Don River in Russia 45,000 to 42,000 years ago. The oldest levels at Kostenki underlie a volcanic ash horizon identified as the Campanian Ignimbrite Y5 tephra that is dated elsewhere to about 40,000 years ago. The occupation layers contain bone and ivory artifacts, including possible figurative art, and fossil shells imported more than 500 kilometers. Thus, modern humans appeared on the central plain of Eastern Europe as early as anywhere else in northern Eurasia.

  19. Sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses

    PubMed Central

    Fang, Shisong; Bai, Tian; Yang, Lei; Wang, Xin; Peng, Bo; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Zhu, Wenfei; Wang, Dayan; Cheng, Jinquan; Shu, Yuelong

    2016-01-01

    Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014. From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected until November 2015. The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city. Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016. Similar viruses were identified in environmental samples collected in the LPMs and the patients. In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study. The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections. Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance. PMID:27485495

  20. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex.

    PubMed

    Self, Matthew W; Peters, Judith C; Possel, Jessy K; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C; Roelfsema, Pieter R

    2016-03-01

    Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex. PMID:27015604

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

    PubMed Central

    Richards, Michael P.; Trinkaus, Erik

    2009-01-01

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

  2. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex

    PubMed Central

    Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C.; Roelfsema, Pieter R.

    2016-01-01

    Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons’ receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex. PMID:27015604

  3. Sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses.

    PubMed

    Fang, Shisong; Bai, Tian; Yang, Lei; Wang, Xin; Peng, Bo; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Zhu, Wenfei; Wang, Dayan; Cheng, Jinquan; Shu, Yuelong

    2016-01-01

    Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014. From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected until November 2015. The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city. Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016. Similar viruses were identified in environmental samples collected in the LPMs and the patients. In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study. The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections. Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance. PMID:27485495

  4. Early humans' egalitarian politics: runaway synergistic competition under an adapted veil of ignorance.

    PubMed

    Harvey, Marc

    2014-09-01

    This paper proposes a model of human uniqueness based on an unusual distinction between two contrasted kinds of political competition and political status: (1) antagonistic competition, in quest of dominance (antagonistic status), a zero-sum, self-limiting game whose stake--who takes what, when, how--summarizes a classical definition of politics (Lasswell 1936), and (2) synergistic competition, in quest of merit (synergistic status), a positive-sum, self-reinforcing game whose stake becomes "who brings what to a team's common good." In this view, Rawls's (1971) famous virtual "veil of ignorance" mainly conceals politics' antagonistic stakes so as to devise the principles of a just, egalitarian society, yet without providing any means to enforce these ideals (Sen 2009). Instead, this paper proposes that human uniqueness flourished under a real "adapted veil of ignorance" concealing the steady inflation of synergistic politics which resulted from early humans' sturdy egalitarianism. This proposition divides into four parts: (1) early humans first stumbled on a purely cultural means to enforce a unique kind of within-team antagonistic equality--dyadic balanced deterrence thanks to handheld weapons (Chapais 2008); (2) this cultural innovation is thus closely tied to humans' darkest side, but it also launched the cumulative evolution of humans' brightest qualities--egalitarian team synergy and solidarity, together with the associated synergistic intelligence, culture, and communications; (3) runaway synergistic competition for differential merit among antagonistically equal obligate teammates is the single politically selective mechanism behind the cumulative evolution of all these brighter qualities, but numerous factors to be clarified here conceal this mighty evolutionary driver; (4) this veil of ignorance persists today, which explains why humans' unique prosocial capacities are still not clearly understood by science. The purpose of this paper is to start lifting

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

    PubMed Central

    Niewoehner, Wesley A.

    2001-01-01

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

  6. Early humans' egalitarian politics: runaway synergistic competition under an adapted veil of ignorance.

    PubMed

    Harvey, Marc

    2014-09-01

    This paper proposes a model of human uniqueness based on an unusual distinction between two contrasted kinds of political competition and political status: (1) antagonistic competition, in quest of dominance (antagonistic status), a zero-sum, self-limiting game whose stake--who takes what, when, how--summarizes a classical definition of politics (Lasswell 1936), and (2) synergistic competition, in quest of merit (synergistic status), a positive-sum, self-reinforcing game whose stake becomes "who brings what to a team's common good." In this view, Rawls's (1971) famous virtual "veil of ignorance" mainly conceals politics' antagonistic stakes so as to devise the principles of a just, egalitarian society, yet without providing any means to enforce these ideals (Sen 2009). Instead, this paper proposes that human uniqueness flourished under a real "adapted veil of ignorance" concealing the steady inflation of synergistic politics which resulted from early humans' sturdy egalitarianism. This proposition divides into four parts: (1) early humans first stumbled on a purely cultural means to enforce a unique kind of within-team antagonistic equality--dyadic balanced deterrence thanks to handheld weapons (Chapais 2008); (2) this cultural innovation is thus closely tied to humans' darkest side, but it also launched the cumulative evolution of humans' brightest qualities--egalitarian team synergy and solidarity, together with the associated synergistic intelligence, culture, and communications; (3) runaway synergistic competition for differential merit among antagonistically equal obligate teammates is the single politically selective mechanism behind the cumulative evolution of all these brighter qualities, but numerous factors to be clarified here conceal this mighty evolutionary driver; (4) this veil of ignorance persists today, which explains why humans' unique prosocial capacities are still not clearly understood by science. The purpose of this paper is to start lifting

  7. Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus.

    PubMed

    Suderman, Matthew; McGowan, Patrick O; Sasaki, Aya; Huang, Tony C T; Hallett, Michael T; Meaney, Michael J; Turecki, Gustavo; Szyf, Moshe

    2012-10-16

    Early life experience is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. However, it is unlikely that such effects completely capture the evolutionarily conserved epigenetic mechanisms of early adaptation to environment. Here we present DNA methylation profiles spanning 6.5 million base pairs centered at the NR3C1 gene in the hippocampus of humans who experienced abuse as children and nonabused controls. We compare these profiles to corresponding DNA methylation profiles in rats that received differential levels of maternal care. The profiles of both species reveal hundreds of DNA methylation differences associated with early life experience distributed across the entire region in nonrandom patterns. For instance, methylation differences tend to cluster by genomic location, forming clusters covering as many as 1 million bases. Even more surprisingly, these differences seem to specifically target regulatory regions such as gene promoters, particularly those of the protocadherin α, β, and γ gene families. Beyond these high-level similarities, more detailed analyses reveal methylation differences likely stemming from the significant biological and environmental differences between species. These results provide support for an analogous cross-species epigenetic regulatory response at the level of the genomic region to early life experience. PMID:23045659

  8. Early Dengue Virus Infection in Human Skin: A Cycle of Inflammation and Infectivity.

    PubMed

    Ivory, Matthew O; Birchall, James C; Piguet, Vincent

    2015-07-01

    Early events during dengue virus (DENV) infection remain poorly understood. In this issue, Schaeffer and colleagues employ ex vivo human skin cells to investigate viral infection. They show that skin-resident immune cells are infected by DENV and that their infectability is increased in the inflammatory skin conditions (especially those in which IL-4 is released) that accompany the mosquito bites transmitting the virus.

  9. Feasibility of terahertz reflectometry for discrimination of human early gastric cancers

    PubMed Central

    Ji, Young Bin; Park, Chan Hyuk; Kim, Hyunki; Kim, Sang-Hoon; Lee, Gyu Min; Noh, Sam Kyu; Jeon, Tae-In; Son, Joo-Hiuk; Huh, Yong-Min; Haam, Seungjoo; Oh, Seung Jae; Lee, Sang Kil; Suh, Jin-Suck

    2015-01-01

    We have investigated the feasibility of THz time-domain reflectometry for the discrimination of human early gastric cancer (EGC) from the normal gastric region. Eight fresh EGC tissues, which were resected by endoscopic submucosal dissection, were studied. Of them, six lesions were well discriminated on THz images and the regions well correlated with tumor regions on pathologically mapped images. Four THz parameters could be suggested for quantitative discrimination of EGCs. PMID:25909023

  10. Human Herpesvirus 6 Latently Infects Early Bone Marrow Progenitors In Vivo

    PubMed Central

    Luppi, Mario; Barozzi, Patrizia; Morris, Christine; Maiorana, Antonio; Garber, Richard; Bonacorsi, Goretta; Donelli, Amedea; Marasca, Roberto; Tabilio, Antonio; Torelli, Giuseppe

    1999-01-01

    We have studied the in vivo tropism of human herpesvirus 6 (HHV-6) for hemopoietic cells in patients with latent HHV-6 infection. Having used a variety of cell purification, molecular, cytogenetic, and immunocytochemical procedures, we report the first evidence that HHV-6 latently infects early bone marrow progenitor cells and that HHV-6 may be transmitted longitudinally to cells which differentiate along the committed pathways. PMID:9847383

  11. Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi

    PubMed Central

    Dykan, Andrey; Rachakonda, Girish; Villalta, Fernando; Mandape, Sammed N.; Lima, Maria F.; Pratap, Siddharth; Nde, Pius N.

    2016-01-01

    The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF-β dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy

  12. Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi.

    PubMed

    Udoko, Aniekanabassi N; Johnson, Candice A; Dykan, Andrey; Rachakonda, Girish; Villalta, Fernando; Mandape, Sammed N; Lima, Maria F; Pratap, Siddharth; Nde, Pius N

    2016-01-01

    The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF-β dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy

  13. Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi.

    PubMed

    Udoko, Aniekanabassi N; Johnson, Candice A; Dykan, Andrey; Rachakonda, Girish; Villalta, Fernando; Mandape, Sammed N; Lima, Maria F; Pratap, Siddharth; Nde, Pius N

    2016-01-01

    The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF-β dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy

  14. Monitoring of human populations for early markers of cadmium toxicity: A review

    SciTech Connect

    Fowler, Bruce A.

    2009-08-01

    Exposure of human populations to cadmium (Cd) from air, food and water may produce effects in organs such as the kidneys, liver, lungs, cardiovascular, immune and reproductive systems. Since Cd has been identified as a human carcinogen, biomarkers for early detection of susceptibility to cancer are of an importance to public health. The ability to document Cd exposure and uptake of this element through biological monitoring is a first step towards understanding its health effects. Interpretation and application of biological monitoring data for predicting human health outcomes require correlation with biological measures of organ system responses to the documented exposure. Essential to this understanding is the detection and linkage of early biological responses toxic effects in target cell populations. Fortunately, advances in cell biology have resulted in the development of pre-clinical biological markers (biomarkers) that demonstrate measurable and characteristic molecular changes in organ systems following chemical exposures that occur prior to the onset of overt clinical disease or development of cancer. Technical advances have rendered a number of these biomarkers practical for monitoring Cd-exposed human populations. Biomarkers will be increasingly important in relation to monitoring effects from the exposure to new Cd-based high technology materials. For example, cadmium-selenium (CdSe), nano-materials made from combinations of these elements have greatly altered cellular uptake characteristics due to particle size. These differences may greatly alter effects at the target cell level and hence risks for organ toxicities from such exposures. The value of validated biomarkers for early detection of systemic Cd-induced effects in humans cannot be underestimated due to the rapid expansion of nano-material technologies. This review will attempt to briefly summarize the applications, to date, of biomarker endpoints for assessing target organ system effects in

  15. Tools to Support Human Factors and Systems Engineering Interactions During Early Analysis

    NASA Technical Reports Server (NTRS)

    Thronesbery, Carroll; Malin, Jane T.; Holden, Kritina; Smith, Danielle Paige

    2006-01-01

    We describe an approach and existing software tool support for effective interactions between human factors engineers and systems engineers in early analysis activities during system acquisition. We examine the tasks performed during this stage, emphasizing those tasks where system engineers and human engineers interact. The Concept of Operations (ConOps) document is an important product during this phase, and particular attention is paid to its influences on subsequent acquisition activities. Understanding this influence helps ConOps authors describe a complete system concept that guides subsequent acquisition activities. We identify commonly used system engineering and human engineering tools and examine how they can support the specific tasks associated with system definition. We identify possible gaps in the support of these tasks, the largest of which appears to be creating the ConOps document itself. Finally, we outline the goals of our future empirical investigations of tools to support system concept definition.

  16. Tools to Support Human Factors and Systems Engineering Interactions During Early Analysis

    NASA Technical Reports Server (NTRS)

    Thronesbery, Carroll; Malin, Jane T.; Holden, Kritina; Smith, Danielle Paige

    2005-01-01

    We describe an approach and existing software tool support for effective interactions between human factors engineers and systems engineers in early analysis activities during system acquisition. We examine the tasks performed during this stage, emphasizing those tasks where system engineers and human engineers interact. The Concept of Operations (ConOps) document is an important product during this phase, and particular attention is paid to its influences on subsequent acquisition activities. Understanding this influence helps ConOps authors describe a complete system concept that guides subsequent acquisition activities. We identify commonly used system engineering and human engineering tools and examine how they can support the specific tasks associated with system definition. We identify possible gaps in the support of these tasks, the largest of which appears to be creating the ConOps document itself. Finally, we outline the goals of our future empirical investigations of tools to support system concept definition.

  17. Metacarpal torsion in apes, humans, and early Australopithecus: implications for manipulatory abilities.

    PubMed

    Drapeau, Michelle S M

    2015-01-01

    Human hands, when compared to that of apes, have a series of adaptations to facilitate manipulation. Numerous studies have shown that Australopithecus afarensis and Au. africanus display some of these adaptations, such as a longer thumb relative to the other fingers, asymmetric heads on the second and fifth metacarpals, and orientation of the second metacarpal joints with the trapezium and capitate away from the sagittal plane, while lacking others such as a very mobile fifth metacarpal, a styloid process on the third, and a flatter metacarpo-trapezium articulation, suggesting some adaptation to manipulation but more limited than in humans. This paper explores variation in metacarpal torsion, a trait said to enhance manipulation, in humans, apes, early australopithecines and specimens from Swartkrans. This study shows that humans are different from large apes in torsion of the third and fourth metacarpals. Humans are also characterized by wedge-shaped bases of the third and fourth metacarpals, making the metacarpal-base row very arched mediolaterally and placing the ulnar-most metacarpals in a position that facilitate opposition to the thumb in power or cradle grips. The third and fourth metacarpals of Au. afarensis are very human-like, suggesting that the medial palm was already well adapted for these kinds of grips in that taxon. Au. africanus present a less clear human-like morphology, suggesting, perhaps, that the medial palm was less suited to human-like manipulation in that taxa than in Au. afarensis. Overall, this study supports previous studies on Au. afarensis and Au. africanus that these taxa had derived hand morphology with some adaptation to human-like power and precision grips and support the hypothesis that dexterous hands largely predated Homo. PMID:26500820

  18. Metacarpal torsion in apes, humans, and early Australopithecus: implications for manipulatory abilities.

    PubMed

    Drapeau, Michelle S M

    2015-01-01

    Human hands, when compared to that of apes, have a series of adaptations to facilitate manipulation. Numerous studies have shown that Australopithecus afarensis and Au. africanus display some of these adaptations, such as a longer thumb relative to the other fingers, asymmetric heads on the second and fifth metacarpals, and orientation of the second metacarpal joints with the trapezium and capitate away from the sagittal plane, while lacking others such as a very mobile fifth metacarpal, a styloid process on the third, and a flatter metacarpo-trapezium articulation, suggesting some adaptation to manipulation but more limited than in humans. This paper explores variation in metacarpal torsion, a trait said to enhance manipulation, in humans, apes, early australopithecines and specimens from Swartkrans. This study shows that humans are different from large apes in torsion of the third and fourth metacarpals. Humans are also characterized by wedge-shaped bases of the third and fourth metacarpals, making the metacarpal-base row very arched mediolaterally and placing the ulnar-most metacarpals in a position that facilitate opposition to the thumb in power or cradle grips. The third and fourth metacarpals of Au. afarensis are very human-like, suggesting that the medial palm was already well adapted for these kinds of grips in that taxon. Au. africanus present a less clear human-like morphology, suggesting, perhaps, that the medial palm was less suited to human-like manipulation in that taxa than in Au. afarensis. Overall, this study supports previous studies on Au. afarensis and Au. africanus that these taxa had derived hand morphology with some adaptation to human-like power and precision grips and support the hypothesis that dexterous hands largely predated Homo.

  19. Metacarpal torsion in apes, humans, and early Australopithecus: implications for manipulatory abilities

    PubMed Central

    2015-01-01

    Human hands, when compared to that of apes, have a series of adaptations to facilitate manipulation. Numerous studies have shown that Australopithecus afarensis and Au. africanus display some of these adaptations, such as a longer thumb relative to the other fingers, asymmetric heads on the second and fifth metacarpals, and orientation of the second metacarpal joints with the trapezium and capitate away from the sagittal plane, while lacking others such as a very mobile fifth metacarpal, a styloid process on the third, and a flatter metacarpo-trapezium articulation, suggesting some adaptation to manipulation but more limited than in humans. This paper explores variation in metacarpal torsion, a trait said to enhance manipulation, in humans, apes, early australopithecines and specimens from Swartkrans. This study shows that humans are different from large apes in torsion of the third and fourth metacarpals. Humans are also characterized by wedge-shaped bases of the third and fourth metacarpals, making the metacarpal-base row very arched mediolaterally and placing the ulnar-most metacarpals in a position that facilitate opposition to the thumb in power or cradle grips. The third and fourth metacarpals of Au. afarensis are very human-like, suggesting that the medial palm was already well adapted for these kinds of grips in that taxon. Au. africanus present a less clear human-like morphology, suggesting, perhaps, that the medial palm was less suited to human-like manipulation in that taxa than in Au. afarensis. Overall, this study supports previous studies on Au. afarensis and Au. africanus that these taxa had derived hand morphology with some adaptation to human-like power and precision grips and support the hypothesis that dexterous hands largely predated Homo. PMID:26500820

  20. The Human Early-Life Exposome (HELIX): Project Rationale and Design

    PubMed Central

    Slama, Rémy; Robinson, Oliver; Chatzi, Leda; Coen, Muireann; van den Hazel, Peter; Thomsen, Cathrine; Wright, John; Athersuch, Toby J.; Avellana, Narcis; Basagaña, Xavier; Brochot, Celine; Bucchini, Luca; Bustamante, Mariona; Carracedo, Angel; Casas, Maribel; Estivill, Xavier; Fairley, Lesley; van Gent, Diana; Gonzalez, Juan R.; Granum, Berit; Gražulevicˇiene˙, Regina; Gutzkow, Kristine B.; Julvez, Jordi; Keun, Hector C.; Kogevinas, Manolis; McEachan, Rosemary R.C.; Meltzer, Helle Margrete; Sabidó, Eduard; Schwarze, Per E.; Siroux, Valérie; Sunyer, Jordi; Want, Elizabeth J.; Zeman, Florence; Nieuwenhuijsen, Mark J.

    2014-01-01

    Background: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure–health effect relationships. The “exposome” concept encompasses the totality of exposures from conception onward, complementing the genome. Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the “early-life exposome.” Here we describe the general design of the project. Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother–child pairs, and biomarkers will be measured in a subset of 1,200 mother–child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure–response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome. Citation: Vrijheid M, Slama R, Robinson O, Chatzi L, Coen M, van den Hazel P

  1. Involvement of human internal globus pallidus in the early modulation of cortical error-related activity.

    PubMed

    Herrojo Ruiz, María; Huebl, Julius; Schönecker, Thomas; Kupsch, Andreas; Yarrow, Kielan; Krauss, Joachim K; Schneider, Gerd-Helge; Kühn, Andrea A

    2014-06-01

    The detection and assessment of errors are a prerequisite to adapt behavior and improve future performance. Error monitoring is afforded by the interplay between cortical and subcortical neural systems. Ample evidence has pointed to a specific cortical error-related evoked potential, the error-related negativity (ERN), during the detection and evaluation of response errors. Recent models of reinforcement learning implicate the basal ganglia (BG) in early error detection following the learning of stimulus-response associations and in the modulation of the cortical ERN. To investigate the influence of the human BG motor output activity on the cortical ERN during response errors, we recorded local field potentials from the sensorimotor area of the internal globus pallidus and scalp electroencephalogram representing activity from the posterior medial frontal cortex in patients with idiopathic dystonia (hands not affected) during a flanker task. In error trials, a specific pallidal error-related potential arose 60 ms prior to the cortical ERN. The error-related changes in pallidal activity-characterized by theta oscillations-were predictive of the cortical error-related activity as assessed by Granger causality analysis. Our findings show an early modulation of error-related activity in the human pallidum, suggesting that pallidal output influences the cortex at an early stage of error detection.

  2. Structural analysis of the major immediate early gene of human cytomegalovirus

    SciTech Connect

    Stenberg, R.M.; Thomsen, D.R.; Stinski, M.F.

    1984-01-01

    The most abundant species of human cytomegalovirus (Towne) immediate early polysome-associated RNA originates from a region of ca. 2.8 kilobases within the XbaI-E DNA fragment. These sequences code for a 1.95-kilobase mRNA and are referred to as immediate early coding region one. The authors have utilized the nuclease mapping technique of Berk and Sharp to examine this gene in detail. Cloned fragments of human cytomegalovirus DNA, either labeled with /sup 32/P in vivo or end labeled in vitro at the 5' or 3' termini, were hybridized to immediate early polysome-associated RNA. The hybrids were treated with single-strand-specific nuclease and subjected to electrophoresis in either neutral or denaturing gels. The major transcript was shown to be spliced molecule containing a 3' terminal exon of 1341 nucleotides. The sequence of the exons as well as the locations of the intro-exon splice junctions were determined. The predicted molecular weight of the polypeptide originating from this region was estimated to be 64,000. The properties of the viral gene and its protein product are discussed.

  3. Markov-chain approach to the distribution of ancestors in species of biparental reproduction.

    PubMed

    Caruso, M; Jarne, C

    2014-08-01

    We studied how to obtain a distribution for the number of ancestors in species of sexual reproduction. Present models concentrate on the estimation of distributions repetitions of ancestors in genealogical trees. It has been shown that it is not possible to reconstruct the genealogical history of each species along all its generations by means of a geometric progression. This analysis demonstrates that it is possible to rebuild the tree of progenitors by modeling the problem with a Markov chain. For each generation, the maximum number of possible ancestors is different. This presents huge problems for the resolution. We found a solution through a dilation of the sample space, although the distribution defined there takes smaller values with respect to the initial problem. In order to correct the distribution for each generation, we introduced the invariance under a gauge (local) group of dilations. These ideas can be used to study the interaction of several processes and provide a new approach on the problem of the common ancestor. In the same direction, this model also provides some elements that can be used to improve models of animal reproduction.

  4. Combining information from ancestors and personal experiences to predict individual differences in developmental trajectories.

    PubMed

    Stamps, Judy A; Krishnan, V V

    2014-11-01

    A persistent question in biology is how information from ancestors combines with personal experiences over the lifetime to affect the developmental trajectories of phenotypic traits. We address this question by modeling individual differences in behavioral developmental trajectories on the basis of two assumptions: (1) differences among individuals in the behavior expressed at birth or hatching are based on information from their ancestors (via genes, epigenes, and prenatal maternal effects), and (2) information from ancestors is combined with information from personal experiences over ontogeny via Bayesian updating. The model predicts relationships between the means and the variability of the behavior expressed by neonates and the subsequent developmental trajectories of their behavior when every individual is reared under the same environmental conditions. Several predictions of the model are supported by data from previous studies of behavioral development, for example, that the temporal stability of personality will increase with age and that the intercepts and slopes of developmental trajectories for boldness will be negatively correlated across individuals or genotypes when subjects are raised in safe environments. We describe how other specific predictions of the model can be used to test the hypothesis that information from ancestors and information from personal experiences are combined via nonadditive, Bayesian-like processes. PMID:25325748

  5. Markov-chain approach to the distribution of ancestors in species of biparental reproduction

    NASA Astrophysics Data System (ADS)

    Caruso, M.; Jarne, C.

    2014-08-01

    We studied how to obtain a distribution for the number of ancestors in species of sexual reproduction. Present models concentrate on the estimation of distributions repetitions of ancestors in genealogical trees. It has been shown that it is not possible to reconstruct the genealogical history of each species along all its generations by means of a geometric progression. This analysis demonstrates that it is possible to rebuild the tree of progenitors by modeling the problem with a Markov chain. For each generation, the maximum number of possible ancestors is different. This presents huge problems for the resolution. We found a solution through a dilation of the sample space, although the distribution defined there takes smaller values with respect to the initial problem. In order to correct the distribution for each generation, we introduced the invariance under a gauge (local) group of dilations. These ideas can be used to study the interaction of several processes and provide a new approach on the problem of the common ancestor. In the same direction, this model also provides some elements that can be used to improve models of animal reproduction.

  6. Integration of Morphological Data into Molecular Phylogenetic Analysis: Toward the Identikit of the Stylasterid Ancestor.

    PubMed

    Puce, Stefania; Pica, Daniela; Schiaparelli, Stefano; Negrisolo, Enrico

    2016-01-01

    Stylasteridae is a hydroid family including 29 worldwide-distributed genera, all provided with a calcareous skeleton. They are abundant in shallow and deep waters and represent an important component of marine communities. In the present paper, we studied the evolution of ten morphological characters, currently used in stylasterid taxonomy, using a phylogenetic approach. Our results indicate that stylasterid morphology is highly plastic and that many events of independent evolution and reversion have occurred. Our analysis also allows sketching a possible identikit of the stylasterid ancestor. It had calcareous skeleton, reticulate-granular coenosteal texture, polyps randomly arranged, gastrostyle, and dactylopore spines, while lacking a gastropore lip and dactylostyles. If the ancestor had single or double/multiple chambered gastropore tube is uncertain. These data suggest that the ancestor was similar to the extant genera Cyclohelia and Stellapora. Our investigation is the first attempt to integrate molecular and morphological information to clarify the stylasterid evolutionary scenario and represents the first step to infer the stylasterid ancestor morphology. PMID:27537333

  7. Analyzing the Rate at Which Languages Lose the Influence of a Common Ancestor

    ERIC Educational Resources Information Center

    Rafferty, Anna N.; Griffiths, Thomas L.; Klein, Dan

    2014-01-01

    Analyzing the rate at which languages change can clarify whether similarities across languages are solely the result of cognitive biases or might be partially due to descent from a common ancestor. To demonstrate this approach, we use a simple model of language evolution to mathematically determine how long it should take for the distribution over…

  8. Genome sequence and annotation of Trichoderma parareesei, the ancestor of the cellulase producer Trichoderma reesei

    DOE PAGES

    Yang, Dongqing; Pomraning, Kyle; Kopchinskiy, Alexey; Karimi, Aghcheh Razieh; Atanasova, Lea; Chenthamara, Komal; Baker, Scott E.; Zhang, Ruifu; Shen, Qirong; Freitag, Michael; et al

    2015-08-13

    The filamentous fungus Trichoderma parareesei is the asexually reproducing ancestor of Trichoderma reesei, the holomorphic industrial producer of cellulase and hemicellulase. Here, we present the genome sequence of the T. parareesei type strain CBS 125925, which contains genes for 9,318 proteins.

  9. The compact Brachypodium genome conserves centromeric regions of a common ancestor with wheat and rice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The evolution of five chromosomes of Brachypodium distachyon from a 12-chromosome ancestor of all grasses by dysploidy raises an interesting question about the fate of redundant centromeres. Three independent but complementary approaches were pursued to study centromeric region homologies among the ...

  10. Integration of Morphological Data into Molecular Phylogenetic Analysis: Toward the Identikit of the Stylasterid Ancestor

    PubMed Central

    Puce, Stefania; Pica, Daniela; Schiaparelli, Stefano; Negrisolo, Enrico

    2016-01-01

    Stylasteridae is a hydroid family including 29 worldwide-distributed genera, all provided with a calcareous skeleton. They are abundant in shallow and deep waters and represent an important component of marine communities. In the present paper, we studied the evolution of ten morphological characters, currently used in stylasterid taxonomy, using a phylogenetic approach. Our results indicate that stylasterid morphology is highly plastic and that many events of independent evolution and reversion have occurred. Our analysis also allows sketching a possible identikit of the stylasterid ancestor. It had calcareous skeleton, reticulate-granular coenosteal texture, polyps randomly arranged, gastrostyle, and dactylopore spines, while lacking a gastropore lip and dactylostyles. If the ancestor had single or double/multiple chambered gastropore tube is uncertain. These data suggest that the ancestor was similar to the extant genera Cyclohelia and Stellapora. Our investigation is the first attempt to integrate molecular and morphological information to clarify the stylasterid evolutionary scenario and represents the first step to infer the stylasterid ancestor morphology. PMID:27537333

  11. Effect of reference population size and available ancestor genotypes on imputation of Mexican Holstein genotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of reference population size and the availability of information from genotyped ancestors on the accuracy of imputation of single nucleotide polymorphisms (SNPs) were investigated for Mexican Holstein cattle. Three scenarios for reference population size were examined: (1) a local popula...

  12. Combining information from ancestors and personal experiences to predict individual differences in developmental trajectories.

    PubMed

    Stamps, Judy A; Krishnan, V V

    2014-11-01

    A persistent question in biology is how information from ancestors combines with personal experiences over the lifetime to affect the developmental trajectories of phenotypic traits. We address this question by modeling individual differences in behavioral developmental trajectories on the basis of two assumptions: (1) differences among individuals in the behavior expressed at birth or hatching are based on information from their ancestors (via genes, epigenes, and prenatal maternal effects), and (2) information from ancestors is combined with information from personal experiences over ontogeny via Bayesian updating. The model predicts relationships between the means and the variability of the behavior expressed by neonates and the subsequent developmental trajectories of their behavior when every individual is reared under the same environmental conditions. Several predictions of the model are supported by data from previous studies of behavioral development, for example, that the temporal stability of personality will increase with age and that the intercepts and slopes of developmental trajectories for boldness will be negatively correlated across individuals or genotypes when subjects are raised in safe environments. We describe how other specific predictions of the model can be used to test the hypothesis that information from ancestors and information from personal experiences are combined via nonadditive, Bayesian-like processes.

  13. Human transgenerational responses to early-life experience: potential impact on development, health and biomedical research.

    PubMed

    Pembrey, Marcus; Saffery, Richard; Bygren, Lars Olov

    2014-09-01

    Mammalian experiments provide clear evidence of male line transgenerational effects on health and development from paternal or ancestral early-life exposures such as diet or stress. The few human observational studies to date suggest (male line) transgenerational effects exist that cannot easily be attributed to cultural and/or genetic inheritance. Here we summarise relevant studies, drawing attention to exposure sensitive periods in early life and sex differences in transmission and offspring outcomes. Thus, variation, or changes, in the parental/ancestral environment may influence phenotypic variation for better or worse in the next generation(s), and so contribute to common, non-communicable disease risk including sex differences. We argue that life-course epidemiology should be reframed to include exposures from previous generations, keeping an open mind as to the mechanisms that transmit this information to offspring. Finally, we discuss animal experiments, including the role of epigenetic inheritance and non-coding RNAs, in terms of what lessons can be learnt for designing and interpreting human studies. This review was developed initially as a position paper by the multidisciplinary Network in Epigenetic Epidemiology to encourage transgenerational research in human cohorts.

  14. Early human use of marine resources and pigment in South Africa during the Middle Pleistocene.

    PubMed

    Marean, Curtis W; Bar-Matthews, Miryam; Bernatchez, Jocelyn; Fisher, Erich; Goldberg, Paul; Herries, Andy I R; Jacobs, Zenobia; Jerardino, Antonieta; Karkanas, Panagiotis; Minichillo, Tom; Nilssen, Peter J; Thompson, Erin; Watts, Ian; Williams, Hope M

    2007-10-18

    Genetic and anatomical evidence suggests that Homo sapiens arose in Africa between 200 and 100 thousand years (kyr) ago, and recent evidence indicates symbolic behaviour may have appeared approximately 135-75 kyr ago. From 195-130 kyr ago, the world was in a fluctuating but predominantly glacial stage (marine isotope stage MIS6); much of Africa was cooler and drier, and dated archaeological sites are rare. Here we show that by approximately 164 kyr ago (+/-12 kyr) at Pinnacle Point (on the south coast of South Africa) humans expanded their diet to include marine resources, perhaps as a response to these harsh environmental conditions. The earliest previous evidence for human use of marine resources and coastal habitats was dated to approximately 125 kyr ago. Coincident with this diet and habitat expansion is an early use and modification of pigment, probably for symbolic behaviour, as well as the production of bladelet stone tool technology, previously dated to post-70 kyr ago. Shellfish may have been crucial to the survival of these early humans as they expanded their home ranges to include coastlines and followed the shifting position of the coast when sea level fluctuated over the length of MIS6. PMID:17943129

  15. From the Cover: Feature Article: Ecosystem variability and early human habitats in eastern Africa

    NASA Astrophysics Data System (ADS)

    Magill, Clayton R.; Ashley, Gail M.; Freeman, Katherine H.

    2013-01-01

    The role of savannas during the course of early human evolution has been debated for nearly a century, in part because of difficulties in characterizing local ecosystems from fossil and sediment records. Here, we present high-resolution lipid biomarker and isotopic signatures for organic matter preserved in lake sediments at Olduvai Gorge during a key juncture in human evolution about 2.0 Ma-the emergence and dispersal of Homo erectus (sensu lato). Using published data for modern plants and soils, we construct a framework for ecological interpretations of stable carbon-isotope compositions (expressed as δ13C values) of lipid biomarkers from ancient plants. Within this framework, δ13C values for sedimentary leaf lipids and total organic carbon from Olduvai Gorge indicate recurrent ecosystem variations, where open C4 grasslands abruptly transitioned to closed C3 forests within several hundreds to thousands of years. Carbon-isotopic signatures correlate most strongly with Earth's orbital geometry (precession), and tropical sea-surface temperatures are significant secondary predictors in partial regression analyses. The scale and pace of repeated ecosystem variations at Olduvai Gorge contrast with long-held views of directional or stepwise aridification and grassland expansion in eastern Africa during the early Pleistocene and provide a local perspective on environmental hypotheses of human evolution.

  16. The human startle reflex and alcohol cue reactivity: effects of early versus late abstinence.

    PubMed

    Saladin, Michael E; Drobes, David J; Coffey, Scott F; Libet, Julian M

    2002-06-01

    This study investigated the human eyeblink startle reflex as a measure of alcohol cue reactivity. Alcohol-dependent participants early (n = 36) and late (n = 34) in abstinence received presentations of alcohol and water cues. Consistent with previous research, greater salivation and higher ratings of urge to drink occurred in response to the alcohol cues. Differential salivary and urge responding to alcohol versus water cues did not vary as a function of abstinence duration. Of special interest was the finding that startle response magnitudes were relatively elevated to alcohol cues, but only in individuals early in abstinence. Affective ratings of alcohol cues suggested that alcohol cues were perceived as aversive. Methodological and theoretical implications of the findings are discussed.

  17. Early ontogeny of the central benzodiazepine receptor in human embryos and fetuses

    SciTech Connect

    Hebebrand, J.; Hofmann, D.; Reichelt, R.; Schnarr, S.; Knapp, M.; Propping, P.; Foedisch, H.J.

    1988-01-01

    The early ontogeny of the central benzodiazepine receptor (BZR) was investigated in human embryos and fetuses between 7 and 26 weeks of gestation. Brain tissue was gained from terminated pregnancies or spontaneous abortions. Binding studies, which were performed with /sup 3/H-flunitrazepam (FNZ), revealed that specific benzodiazepine binding is already detectable at an embryonal age of 7 weeks post conception. Binding at this early stage can be displaced potently by clonazepam and the inverse agonist ..beta..-CCE. Additionally, /sup 3/H-FNZ binding is enhanced by GABA. Thus, benzodiazepine binding is of the central type. Receptor density increases steeply in whole brain between weeks 8 and 11 of gestation. In frontal cortex receptor density increases gradually between weeks 12 and 26 of gestation. No specific fetal disease entity (including trisomy 21) was consistently associated with exceptionally high or low B/sub max/-values.

  18. New Archaeological Evidence for an Early Human Presence at Monte Verde, Chile

    PubMed Central

    Dillehay, Tom D.; Ocampo, Carlos; Saavedra, José; Sawakuchi, Andre Oliveira; Vega, Rodrigo M.; Pino, Mario; Collins, Michael B.; Scott Cummings, Linda; Arregui, Iván; Villagran, Ximena S.; Hartmann, Gelvam A.; Mella, Mauricio; González, Andrea; Dix, George

    2015-01-01

    Questions surrounding the chronology, place, and character of the initial human colonization of the Americas are a long-standing focus of debate. Interdisciplinary debate continues over the timing of entry, the rapidity and direction of dispersion, the variety of human responses to diverse habitats, the criteria for evaluating the validity of early sites, and the differences and similarities between colonization in North and South America. Despite recent advances in our understanding of these issues, archaeology still faces challenges in defining interdisciplinary research problems, assessing the reliability of the data, and applying new interpretative models. As the debates and challenges continue, new studies take place and previous research reexamined. Here we discuss recent exploratory excavation at and interdisciplinary data from the Monte Verde area in Chile to further our understanding of the first peopling of the Americas. New evidence of stone artifacts, faunal remains, and burned areas suggests discrete horizons of ephemeral human activity in a sandur plain setting radiocarbon and luminescence dated between at least ~18,500 and 14,500 cal BP. Based on multiple lines of evidence, including sedimentary proxies and artifact analysis, we present the probable anthropogenic origins and wider implications of this evidence. In a non-glacial cold climate environment of the south-central Andes, which is challenging for human occupation and for the preservation of hunter-gatherer sites, these horizons provide insight into an earlier context of late Pleistocene human behavior in northern Patagonia. PMID:26580202

  19. Defining the Genomic Signature of Totipotency and Pluripotency during Early Human Development

    PubMed Central

    Galan, Amparo; Diaz-Gimeno, Patricia; Poo, Maria Eugenia; Valbuena, Diana; Sanchez, Eva; Ruiz, Veronica; Dopazo, Joaquin; Montaner, David; Conesa, Ana; Simon, Carlos

    2013-01-01

    The genetic mechanisms governing human pre-implantation embryo development and the in vitro counterparts, human embryonic stem cells (hESCs), still remain incomplete. Previous global genome studies demonstrated that totipotent blastomeres from day-3 human embryos and pluripotent inner cell masses (ICMs) from blastocysts, display unique and differing transcriptomes. Nevertheless, comparative gene expression analysis has revealed that no significant differences exist between hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental progression. To understand early human stages evolution, we developed an undifferentiation network signature (UNS) and applied it to a differential gene expression profile between single blastomeres from day-3 embryos, ICMs and hESCs. This allowed us to establish a unique signature composed of highly interconnected genes characteristic of totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro pluripotency (107 genes), and which are also proprietary according to functional analysis. This systems biology approach has led to an improved understanding of the molecular and signaling processes governing human pre-implantation embryo development, as well as enabling us to comprehend how hESCs might adapt to in vitro culture conditions. PMID:23614026

  20. New Archaeological Evidence for an Early Human Presence at Monte Verde, Chile.

    PubMed

    Dillehay, Tom D; Ocampo, Carlos; Saavedra, José; Sawakuchi, Andre Oliveira; Vega, Rodrigo M; Pino, Mario; Collins, Michael B; Scott Cummings, Linda; Arregui, Iván; Villagran, Ximena S; Hartmann, Gelvam A; Mella, Mauricio; González, Andrea; Dix, George

    2015-01-01

    Questions surrounding the chronology, place, and character of the initial human colonization of the Americas are a long-standing focus of debate. Interdisciplinary debate continues over the timing of entry, the rapidity and direction of dispersion, the variety of human responses to diverse habitats, the criteria for evaluating the validity of early sites, and the differences and similarities between colonization in North and South America. Despite recent advances in our understanding of these issues, archaeology still faces challenges in defining interdisciplinary research problems, assessing the reliability of the data, and applying new interpretative models. As the debates and challenges continue, new studies take place and previous research reexamined. Here we discuss recent exploratory excavation at and interdisciplinary data from the Monte Verde area in Chile to further our understanding of the first peopling of the Americas. New evidence of stone artifacts, faunal remains, and burned areas suggests discrete horizons of ephemeral human activity in a sandur plain setting radiocarbon and luminescence dated between at least ~18,500 and 14,500 cal BP. Based on multiple lines of evidence, including sedimentary proxies and artifact analysis, we present the probable anthropogenic origins and wider implications of this evidence. In a non-glacial cold climate environment of the south-central Andes, which is challenging for human occupation and for the preservation of hunter-gatherer sites, these horizons provide insight into an earlier context of late Pleistocene human behavior in northern Patagonia. PMID:26580202

  1. New Archaeological Evidence for an Early Human Presence at Monte Verde, Chile.

    PubMed

    Dillehay, Tom D; Ocampo, Carlos; Saavedra, José; Sawakuchi, Andre Oliveira; Vega, Rodrigo M; Pino, Mario; Collins, Michael B; Scott Cummings, Linda; Arregui, Iván; Villagran, Ximena S; Hartmann, Gelvam A; Mella, Mauricio; González, Andrea; Dix, George

    2015-01-01

    Questions surrounding the chronology, place, and character of the initial human colonization of the Americas are a long-standing focus of debate. Interdisciplinary debate continues over the timing of entry, the rapidity and direction of dispersion, the variety of human responses to diverse habitats, the criteria for evaluating the validity of early sites, and the differences and similarities between colonization in North and South America. Despite recent advances in our understanding of these issues, archaeology still faces challenges in defining interdisciplinary research problems, assessing the reliability of the data, and applying new interpretative models. As the debates and challenges continue, new studies take place and previous research reexamined. Here we discuss recent exploratory excavation at and interdisciplinary data from the Monte Verde area in Chile to further our understanding of the first peopling of the Americas. New evidence of stone artifacts, faunal remains, and burned areas suggests discrete horizons of ephemeral human activity in a sandur plain setting radiocarbon and luminescence dated between at least ~18,500 and 14,500 cal BP. Based on multiple lines of evidence, including sedimentary proxies and artifact analysis, we present the probable anthropogenic origins and wider implications of this evidence. In a non-glacial cold climate environment of the south-central Andes, which is challenging for human occupation and for the preservation of hunter-gatherer sites, these horizons provide insight into an earlier context of late Pleistocene human behavior in northern Patagonia.

  2. Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle.

    PubMed Central

    Shirazi, Y; Pitha, P M

    1992-01-01

    In this study, we have analyzed the effect of human alpha interferon (IFN-alpha) on a single replication cycle of human immunodeficiency virus type 1 (HIV-1) infection in the lymphocytic cell line CEM-174, which is highly sensitive to the antiviral effects of IFN. Pretreatment of cells with 50 to 500 U of recombinant human IFN-alpha per ml resulted in a marked reduction in viral RNA and protein synthesis. The effect of IFN-alpha was dose dependent and was amplified in multiple infection cycles. IFN-induced inhibition of viral protein synthesis could be detected only when cells were treated with IFN-alpha prior to infection or when IFN-alpha was added up to 10 h postinfection, but not if IFN-alpha was added at the later stages of HIV-1 replication cycle or after the HIV-1 infection was already established. Analysis of the integrated HIV-1 provirus showed a marked decrease in the levels of proviral DNA in IFN-treated cells. Thus, in contrast to the previous studies on established HIV-1 infection in T cells, in which the IFN block appeared to be at the posttranslational level, during de novo infection, IFN-alpha interferes with an early step of HIV-1 replication cycle that occurs prior to the integration of the proviral DNA. These results indicate that the early IFN block of HIV-1 replication, which has been previously observed only in primary marcophages, can also be detected in the IFN-sensitive T cells, indicating that the early IFN block is not limited to macrophages. Images PMID:1738192

  3. From the Cover: Feature Article: Water, plants, and early human habitats in eastern Africa

    NASA Astrophysics Data System (ADS)

    Magill, Clayton R.; Ashley, Gail M.; Freeman, Katherine H.

    2013-01-01

    Water and its influence on plants likely exerted strong adaptive pressures in human evolution. Understanding relationships among water, plants, and early humans is limited both by incomplete terrestrial records of environmental change and by indirect proxy data for water availability. Here we present a continuous record of stable hydrogen-isotope compositions (expressed as δD values) for lipid biomarkers preserved in lake sediments from an early Pleistocene archaeological site in eastern Africa-Olduvai Gorge. We convert sedimentary leaf- and algal-lipid δD values into estimates for ancient source-water δD values by accounting for biochemical, physiological, and environmental influences on isotopic fractionation via published water-lipid enrichment factors for living plants, algae, and recent sediments. Reconstructed precipitation and lake-water δD values, respectively, are consistent with modern isotopic hydrology and reveal that dramatic fluctuations in water availability accompanied ecosystem changes. Drier conditions, indicated by less negative δD values, occur in association with stable carbon-isotopic evidence for open, C4-dominated grassland ecosystems. Wetter conditions, indicated by lower δD values, are associated with expanded woody cover across the ancient landscape. Estimates for ancient precipitation amounts, based on reconstructed precipitation δD values, range between approximately 250 and 700 mm.y-1 and are consistent with modern precipitation data for eastern Africa. We conclude that freshwater availability exerted a substantial influence on eastern African ecosystems and, by extension, was central to early human proliferation during periods of rapid climate change.

  4. Early Detection of Human Epileptic Seizures Based on Intracortical Local Field Potentials.

    PubMed

    Park, Yun S; Hochberg, Leigh R; Eskandar, Emad N; Cash, Sydney S; Truccolo, Wilson

    2013-01-01

    The unpredictability of re-occurring seizures dramatically impacts the quality of life and autonomy of people with epilepsy. Reliable early seizure detection could open new therapeutic possibilities and thus substantially improve quality of life and autonomy. Though many seizure detection studies have shown the potential of scalp electroencephalogram (EEG) and intracranial EEG (iEEG) signals, reliable early detection of human seizures remains elusive in practice. Here, we examined the use of intracortical local field potentials (LFPs) recorded from 4×4-mm(2) 96-microelectrode arrays (MEA) for early detection of human epileptic seizures. We adopted a framework consisting of (1) sampling of intracortical LFPs; (2) denoising of LFPs with the Kalman filter; (3) spectral power estimation in specific frequency bands using 1-sec moving time windows; (4) extraction of statistical features, such as the mean, variance, and Fano factor (calculated across channels) of the power in each frequency band; and (5) cost-sensitive support vector machine (SVM) classification of ictal and interictal samples. We tested the framework in one-participant dataset, including 4 seizures and corresponding interictal recordings preceding each seizure. The participant was a 52-year-old woman suffering from complex partial seizures. LFPs were recorded from an MEA implanted in the participant's left middle temporal gyrus. In this participant, spectral power in 0.3-10 Hz, 20-55 Hz, and 125-250 Hz changed significantly between ictal and interictal epochs. The examined seizure detection framework provided an event-wise sensitivity of 100% (4/4) and only one 20-sec-long false positive event in interictal recordings (likely an undetected subclinical event under further visual inspection), and a detection latency of 4.35 ± 2.21 sec (mean ± std) with respect to iEEG-identified seizure onsets. These preliminary results indicate that intracortical MEA recordings may provide key signals to quickly and

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

    PubMed

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

    2014-04-01

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

  6. [Early human transplants: 60th anniversary of the first successful kidney transplants].

    PubMed

    Gentili, Marc E

    2015-11-01

    First kidney transplant attempts begin with the 20th century: improving vascular sutures, understanding the phenomena of rejection or tolerance, then progress in HLA groups enable early success in the second half of the century. Definition of brain death, use of corticosteroids, radiotherapy and prime immunosuppressors promote the development of transplants. Discover of cyclosporine in the 1980s, and legislative developments augur a new era. Many advances are arising: use of stem cells from the donor, enhancement of Maastricht 3 donor or living donation. Finally organ transplantation remains an immense human adventure, but also scientific and ethic.

  7. Early influence of auditory stimuli on upper-limb movements in young human infants: an overview

    PubMed Central

    Ferronato, Priscilla A. M.; Domellöf, Erik; Rönnqvist, Louise

    2014-01-01

    Given that the auditory system is rather well developed at the end of the third trimester of pregnancy, it is likely that couplings between acoustics and motor activity can be integrated as early as at the beginning of postnatal life. The aim of the present mini-review was to summarize and discuss studies on early auditory-motor integration, focusing particularly on upper-limb movements (one of the most crucial means to interact with the environment) in association with auditory stimuli, to develop further understanding of their significance with regard to early infant development. Many studies have investigated the relationship between various infant behaviors (e.g., sucking, visual fixation, head turning) and auditory stimuli, and established that human infants can be observed displaying couplings between action and environmental sensory stimulation already from just after birth, clearly indicating a propensity for intentional behavior. Surprisingly few studies, however, have investigated the associations between upper-limb movements and different auditory stimuli in newborns and young infants, infants born at risk for developmental disorders/delays in particular. Findings from studies of early auditory-motor interaction support that the developing integration of sensory and motor systems is a fundamental part of the process guiding the development of goal-directed action in infancy, of great importance for continued motor, perceptual, and cognitive development. At-risk infants (e.g., those born preterm) may display increasing central auditory processing disorders, negatively affecting early sensory-motor integration, and resulting in long-term consequences on gesturing, language development, and social communication. Consequently, there is a need for more studies on such implications. PMID:25278927

  8. Early developmental exposures shape trade-offs between acquired and innate immunity in humans

    PubMed Central

    Georgiev, Alexander V.; Kuzawa, Christopher W.; McDade, Thomas W.

    2016-01-01

    Background and objectives Life history theory predicts resource allocation trade-offs between competing functions and processes. We test the hypothesis that relative investment towards innate versus acquired immunity in humans is subject to such trade-offs and that three types of early developmental exposures are particularly salient in shaping adult immunophenotype: (i) pathogen exposure, (ii) nutritional resources; and (iii) extrinsic mortality cues. Methodology We quantified one aspect each of innate and acquired immune function, via C-reactive protein and Epstein–Barr virus antibodies, respectively, in a sample of 1248 men and women from the Philippines (ca. 21.5 years old). Early developmental exposures were assessed via long-term data collected prospectively since participants’ birth (1983–4). We calculated a standardized ratio to assess relative bias towards acquired versus innate immune function and examined its relationship to a suite of predictors via multiple regression. Results In partial support of our predictions, some of the measures of higher pathogen exposure, greater availability of nutritional resources, and lower extrinsic mortality cues in early life were associated with a bias toward acquired immunity in both men and women. The immune profile of women, in particular, appeared to be more sensitive to early life pathogen exposures than those of men. Finally, contrary to prediction, women exhibited a greater relative investment toward innate, not acquired, immunity. Conclusions and implications Early environments can exert considerable influence on the development of immunity. They affect trade-offs between innate and acquired immunity, which show adaptive plasticity and may differ in their influence in men and women. PMID:27530543

  9. The first modern human dispersals across Africa.

    PubMed

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

    2013-01-01

    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.

  10. The First Modern Human Dispersals across Africa

    PubMed Central

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

    2013-01-01

    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

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

    PubMed

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

    2005-11-01

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

  12. Early human use of anadromous salmon in North America at 11,500 y ago.

    PubMed

    Halffman, Carrin M; Potter, Ben A; McKinney, Holly J; Finney, Bruce P; Rodrigues, Antonia T; Yang, Dongya Y; Kemp, Brian M

    2015-10-01

    Salmon represented a critical resource for prehistoric foragers along the North Pacific Rim, and continue to be economically and culturally important; however, the origins of salmon exploitation remain unresolved. Here we report 11,500-y-old salmon associated with a cooking hearth and human burials from the Upward Sun River Site, near the modern extreme edge of salmon habitat in central Alaska. This represents the earliest known human use of salmon in North America. Ancient DNA analyses establish the species as Oncorhynchus keta (chum salmon), and stable isotope analyses indicate anadromy, suggesting that salmon runs were established by at least the terminal Pleistocene. The early use of this resource has important implications for Paleoindian land use, economy, and expansions into northwest North America. PMID:26392548

  13. Human radiation studies: Remembering the early years. Oral history of Julie Langham Grilly, February 3, 1995

    SciTech Connect

    1995-09-01

    Julie Langham Grilly was interviewed by representatives of the US DOE Office of Human Radiation Experiments (OHRE) being the widow of Dr. Wright Langham, an investigator of principal interest of the committee. Her extensive experience with research at LANL was also of interest to the committee. Following a brief biographical sketch, Ms. Grilly relates her early postwar experience and her knowledge of Wright Langham`s involvement in animal research at Los Alamos, radiolanthanum tests on monkeys, Eniwetok tissue examinations, research on tritium uptake in humans, plutonium injections, tritium injections, EDTA, and etc. In addition to illuminating her former husband as a researcher and as an individual, she also relates her remembrances of Louis Hempelman, Enrico Fermi, Oppenheimer, Edward Teller, and many others.

  14. Early human use of anadromous salmon in North America at 11,500 y ago.

    PubMed

    Halffman, Carrin M; Potter, Ben A; McKinney, Holly J; Finney, Bruce P; Rodrigues, Antonia T; Yang, Dongya Y; Kemp, Brian M

    2015-10-01

    Salmon represented a critical resource for prehistoric foragers along the North Pacific Rim, and continue to be economically and culturally important; however, the origins of salmon exploitation remain unresolved. Here we report 11,500-y-old salmon associated with a cooking hearth and human burials from the Upward Sun River Site, near the modern extreme edge of salmon habitat in central Alaska. This represents the earliest known human use of salmon in North America. Ancient DNA analyses establish the species as Oncorhynchus keta (chum salmon), and stable isotope analyses indicate anadromy, suggesting that salmon runs were established by at least the terminal Pleistocene. The early use of this resource has important implications for Paleoindian land use, economy, and expansions into northwest North America.

  15. Early human use of anadromous salmon in North America at 11,500 y ago

    PubMed Central

    Halffman, Carrin M.; Potter, Ben A.; McKinney, Holly J.; Finney, Bruce P.; Rodrigues, Antonia T.; Yang, Dongya Y.; Kemp, Brian M.

    2015-01-01

    Salmon represented a critical resource for prehistoric foragers along the North Pacific Rim, and continue to be economically and culturally important; however, the origins of salmon exploitation remain unresolved. Here we report 11,500-y-old salmon associated with a cooking hearth and human burials from the Upward Sun River Site, near the modern extreme edge of salmon habitat in central Alaska. This represents the earliest known human use of salmon in North America. Ancient DNA analyses establish the species as Oncorhynchus keta (chum salmon), and stable isotope analyses indicate anadromy, suggesting that salmon runs were established by at least the terminal Pleistocene. The early use of this resource has important implications for Paleoindian land use, economy, and expansions into northwest North America. PMID:26392548

  16. Preference for language in early infancy: the human language bias is not speech specific.

    PubMed

    Krentz, Ursula C; Corina, David P

    2008-01-01

    Fundamental to infants' acquisition of their native language is an inherent interest in the language spoken around them over non-linguistic environmental sounds. The following studies explored whether the bias for linguistic signals in hearing infants is specific to speech, or reflects a general bias for all human language, spoken and signed. Results indicate that 6-month-old infants prefer an unfamiliar, visual-gestural language (American Sign Language) over non-linguistic pantomime, but 10-month-olds do not. These data provide evidence against a speech-specific bias in early infancy and provide insights into those properties of human languages that may underlie this language-general attentional bias.

  17. Distinct vestibular effects on early and late somatosensory cortical processing in humans.

    PubMed

    Pfeiffer, Christian; van Elk, Michiel; Bernasconi, Fosco; Blanke, Olaf

    2016-01-15

    In non-human primates several brain areas contain neurons that respond to both vestibular and somatosensory stimulation. In humans, vestibular stimulation activates several somatosensory brain regions and improves tactile perception. However, less is known about the spatio-temporal dynamics of such vestibular-somatosensory interactions in the human brain. To address this issue, we recorded high-density electroencephalography during left median nerve electrical stimulation to obtain Somatosensory Evoked Potentials (SEPs). We analyzed SEPs during vestibular activation following sudden decelerations from constant-velocity (90°/s and 60°/s) earth-vertical axis yaw rotations and SEPs during a non-vestibular control period. SEP analysis revealed two distinct temporal effects of vestibular activation: An early effect (28-32ms post-stimulus) characterized by vestibular suppression of SEP response strength that depended on rotation velocity and a later effect (97-112ms post-stimulus) characterized by vestibular modulation of SEP topographical pattern that was rotation velocity-independent. Source estimation localized these vestibular effects, during both time periods, to activation differences in a distributed cortical network including the right postcentral gyrus, right insula, left precuneus, and bilateral secondary somatosensory cortex. These results suggest that vestibular-somatosensory interactions in humans depend on processing in specific time periods in somatosensory and vestibular cortical regions.

  18. Distinct vestibular effects on early and late somatosensory cortical processing in humans.

    PubMed

    Pfeiffer, Christian; van Elk, Michiel; Bernasconi, Fosco; Blanke, Olaf

    2016-01-15

    In non-human primates several brain areas contain neurons that respond to both vestibular and somatosensory stimulation. In humans, vestibular stimulation activates several somatosensory brain regions and improves tactile perception. However, less is known about the spatio-temporal dynamics of such vestibular-somatosensory interactions in the human brain. To address this issue, we recorded high-density electroencephalography during left median nerve electrical stimulation to obtain Somatosensory Evoked Potentials (SEPs). We analyzed SEPs during vestibular activation following sudden decelerations from constant-velocity (90°/s and 60°/s) earth-vertical axis yaw rotations and SEPs during a non-vestibular control period. SEP analysis revealed two distinct temporal effects of vestibular activation: An early effect (28-32ms post-stimulus) characterized by vestibular suppression of SEP response strength that depended on rotation velocity and a later effect (97-112ms post-stimulus) characterized by vestibular modulation of SEP topographical pattern that was rotation velocity-independent. Source estimation localized these vestibular effects, during both time periods, to activation differences in a distributed cortical network including the right postcentral gyrus, right insula, left precuneus, and bilateral secondary somatosensory cortex. These results suggest that vestibular-somatosensory interactions in humans depend on processing in specific time periods in somatosensory and vestibular cortical regions. PMID:26466979

  19. Neural Correlates of Natural Human Echolocation in Early and Late Blind Echolocation Experts

    PubMed Central

    Thaler, Lore; Arnott, Stephen R.; Goodale, Melvyn A.

    2011-01-01

    Background A small number of blind people are adept at echolocating silent objects simply by producing mouth clicks and listening to the returning echoes. Yet the neural architecture underlying this type of aid-free human echolocation has not been investigated. To tackle this question, we recruited echolocation experts, one early- and one late-blind, and measured functional brain activity in each of them while they listened to their own echolocation sounds. Results When we compared brain activity for sounds that contained both clicks and the returning echoes with brain activity for control sounds that did not contain the echoes, but were otherwise acoustically matched, we found activity in calcarine cortex in both individuals. Importantly, for the same comparison, we did not observe a difference in activity in auditory cortex. In the early-blind, but not the late-blind participant, we also found that the calcarine activity was greater for echoes reflected from surfaces located in contralateral space. Finally, in both individuals, we found activation in middle temporal and nearby cortical regions when they listened to echoes reflected from moving targets. Conclusions These findings suggest that processing of click-echoes recruits brain regions typically devoted to vision rather than audition in both early and late blind echolocation experts. PMID:21633496

  20. Changes in Laminin Expression Pattern during Early Differentiation of Human Embryonic Stem Cells.

    PubMed

    Pook, Martin; Teino, Indrek; Kallas, Ade; Maimets, Toivo; Ingerpuu, Sulev; Jaks, Viljar

    2015-01-01

    Laminin isoforms laminin-511 and -521 are expressed by human embryonic stem cells (hESC) and can be used as a growth matrix to culture these cells under pluripotent conditions. However, the expression of these laminins during the induction of hESC differentiation has not been studied in detail. Furthermore, the data regarding the expression pattern of laminin chains in differentiating hESC is scarce. In the current study we aimed to fill this gap and investigated the potential changes in laminin expression during early hESC differentiation induced by retinoic acid (RA). We found that laminin-511 but not -521 accumulates in the committed cells during early steps of hESC differentiation. We also performed a comprehensive analysis of the laminin chain repertoire and found that pluripotent hESC express a more diverse range of laminin chains than shown previously. In particular, we provide the evidence that in addition to α1, α5, β1, β2 and γ1 chains, hESC express α2, α3, β3, γ2 and γ3 chain proteins and mRNA. Additionally, we found that a variant of laminin α3 chain-145 kDa-accumulated in RA-treated hESC showing that these cells produce prevalently specifically modified version of α3 chain in early phase of differentiation. PMID:26378917

  1. Changes in Laminin Expression Pattern during Early Differentiation of Human Embryonic Stem Cells

    PubMed Central

    Pook, Martin; Teino, Indrek; Kallas, Ade; Maimets, Toivo; Ingerpuu, Sulev; Jaks, Viljar

    2015-01-01

    Laminin isoforms laminin-511 and -521 are expressed by human embryonic stem cells (hESC) and can be used as a growth matrix to culture these cells under pluripotent conditions. However, the expression of these laminins during the induction of hESC differentiation has not been studied in detail. Furthermore, the data regarding the expression pattern of laminin chains in differentiating hESC is scarce. In the current study we aimed to fill this gap and investigated the potential changes in laminin expression during early hESC differentiation induced by retinoic acid (RA). We found that laminin-511 but not -521 accumulates in the committed cells during early steps of hESC differentiation. We also performed a comprehensive analysis of the laminin chain repertoire and found that pluripotent hESC express a more diverse range of laminin chains than shown previously. In particular, we provide the evidence that in addition to α1, α5, β1, β2 and γ1 chains, hESC express α2, α3, β3, γ2 and γ3 chain proteins and mRNA. Additionally, we found that a variant of laminin α3 chain—145 kDa—accumulated in RA-treated hESC showing that these cells produce prevalently specifically modified version of α3 chain in early phase of differentiation. PMID:26378917

  2. Reactivation of Epstein-Barr virus during early infection with human immunodeficiency virus.

    PubMed Central

    Rahman, M A; Kingsley, L A; Atchison, R W; Belle, S; Breinig, M C; Ho, M; Rinaldo, C R

    1991-01-01

    Reactivation of Epstein-Barr virus (EBV) in early human immunodeficiency virus (HIV) infection was investigated in 49 homosexual men who seroconverted to HIV (cases) as compared with 49 matched controls who remained seronegative to HIV during a longitudinal study. EBV infection was reactivated in cases 6 months, but not 12 months, prior to HIV seroconversion as compared with controls and remained reactivated during 18 months of follow-up after HIV seroconversion, as shown by increases in immunoglobulin (Ig) G antibody titers to EBV early antigen. Antibody titers to EBV viral capsid antigen did not differ between cases and controls prior to the time of seroconversion to HIV but were significantly increased among cases by the first seropositive study visit and remained elevated during the 18 months after HIV seroconversion. Total serum IgG levels were increased in cases at the visit of seroconversion, and during 18 months of follow-up, but did not correlate with enhanced IgG production specific for EBV antigens. Significant decreases in numbers of CD4+ cells and increases in numbers of CD8+ cells during this early phase of HIV infection were not associated with changes in patterns of EBV antibody responses. Reactivation of EBV beginning 6 months before HIV seroconversion may have implications regarding the role of this herpesvirus in the pathogenesis of HIV. PMID:1650790

  3. Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques.

    PubMed

    Hessell, Ann J; Jaworski, J Pablo; Epson, Erin; Matsuda, Kenta; Pandey, Shilpi; Kahl, Christoph; Reed, Jason; Sutton, William F; Hammond, Katherine B; Cheever, Tracy A; Barnette, Philip T; Legasse, Alfred W; Planer, Shannon; Stanton, Jeffrey J; Pegu, Amarendra; Chen, Xuejun; Wang, Keyun; Siess, Don; Burke, David; Park, Byung S; Axthelm, Michael K; Lewis, Anne; Hirsch, Vanessa M; Graham, Barney S; Mascola, John R; Sacha, Jonah B; Haigwood, Nancy L

    2016-04-01

    Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1-specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIVSF162P3. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8(+) T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs. PMID:26998834

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

    NASA Astrophysics Data System (ADS)

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

    2007-09-01

    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.

  5. Early embryonic failure: Expression and imprinted status of candidate genes on human chromosome 21

    SciTech Connect

    Sherman, L.S.; Bennett, P.R.; Moore, G.E.

    1994-09-01

    Two cases of maternal uniparental (hetero)disomy for human chromosome 21 (mUPD21) have been identified in a systematic search for UPD in 23 cases of early embryonic failure (EEF). Bi-parental origin of the other chromosome pairs was confirmed using specific VNTR probes or dinucleotide repeat analysis. Both maternally and paternally derived isochromosomes 21q have previously been identified in two individuals with normal phenotypes. Full UPD21 has a different mechanism of origin than uniparental isochromosome 21q and its effect on imprinted genes and phenotypic outcome will therefore not necessarily be the same. EEF associated with mUPD21 suggests that developmentally important genes on HSA 21 may be imprinted such that they are only expressed from either the maternally or paternally derived alleles. We have searched for monoallelic expression of candidate genes on HSA 21 in human pregnancy (CBS, IFNAR, COL6A1) using intragenic DNA polymorphisms. These genes were chosen either because their murine homologues lie in imprinted regions or because they are potentially important in embryogenesis. Once imprinted candidate genes have been identified, their methylation status and expression in normal, early embryonic failure and uniparental disomy 21 pregnancies will be studied. At the same time, a larger number of cases of EEF are being examined to further investigate the incidence of UPD21 in this group.

  6. Early Human Activity (pre-332 BC) in Alexandria, Egypt: New findings in Eastern Harbor Cores

    NASA Astrophysics Data System (ADS)

    Stanley, J.; Landau, E. A.

    2005-12-01

    Historians have long postulated that a settlement called Rhakotis was present on Egypt's Mediterranean coast in the area subsequently occupied by the city of Alexandria. To date, however, the precise position of that site has not been located in the immediate area of the city founded by Alexander the Great. Also undefined are the earliest phases of occupation that pre-date Alexandria on Pharos Island and in the harbour area. A geoarchaeological project emphasizing sediment cores in Alexandria's Eastern Harbour now provides evidence of human occupation adjacent to these settings prior to establishment of Greece's great port in 332 BC. A radiocarbon-dated stratigraphic unit, defined as Middle Sand (III) and older than the 4th century BC, includes locally produced ceramics, along with rock fragments of non-local origin, and increased content of sand-sized heavy mineral and organic matter. Together, these date at least to Egypt's Late Dynastic Period (712-332 BC). Moreover, the geographic positions of core sites containing these markers indicate that early habitation occurred both at Pharos Island and on the mainland where the future Alexandria would be built. New findings in cores recovered in this marine environment are adding to knowledge of both natural processes and effects of human activity in early Alexandria.

  7. Synchrotron FTIR microspectroscopy reveals early adipogenic differentiation of human mesenchymal stem cells at single-cell level.

    PubMed

    Liu, Zhixiao; Tang, Yuzhao; Chen, Feng; Liu, Xia; Liu, Zhaojian; Zhong, Jiajia; Hu, Jun; Lü, Junhong

    2016-09-23

    Human mesenchymal stem cells (hMSCs) have been used as an ideal in vitro model to study human adipogenesis. However, little knowledge of the early stage differentiation greatly hinders our understanding on the mechanism of the adipogenesis processes. In this study, synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy was applied to track the global structural and compositional changes of lipids, proteins and nucleic acids inside individual hMSCs along the time course. The multivariate analysis of the SR-FTIR spectra distinguished the dynamic and significant changes of the lipids and nucleic acid at early differentiation stage. Importantly, changes of lipid structure during early days (Day 1-3) of differentiation might serve as a potential biomarker in identifying the state in early differentiation at single cell level. These results proved that SR-FTIR is a powerful tool to study the stem cell fate determination and early lipogenesis events. PMID:27553281

  8. A More-than-Social Movement: The Post-Human Condition of Quality in the Early Years

    ERIC Educational Resources Information Center

    Arndt, Sonja; Tesar, Marek

    2016-01-01

    This article explores quality in early childhood education by de-elevating the importance of the human subject and experience, and heightening instead a focus on and tensions with the post-human. The argument traces the intricate web of "qualities" woven throughout entanglements of subjects, objects and things that constitute what is…

  9. The Early Development of Human Mirror Mechanisms: Evidence from Electromyographic Recordings at 3 and 6 Months

    ERIC Educational Resources Information Center

    Turati, Chiara; Natale, Elena; Bolognini, Nadia; Senna, Irene; Picozzi, Marta; Longhi, Elena; Cassia, Viola Macchi

    2013-01-01

    In primates and adult humans direct understanding of others' action is provided by mirror mechanisms matching action observation and action execution (e.g. Casile, Caggiano & Ferrari, 2011). Despite the growing body of evidence detailing the existence of these mechanisms in the adult human brain, their origins and early development are…

  10. The (Bio)Politicization of Neuroscience in Australian Early Years Policies: Fostering Brain-Resources "as" Human Capital

    ERIC Educational Resources Information Center

    Millei, Zsuzsa; Joronen, Mikko

    2016-01-01

    At the present, human capital theory (HCT) and neuroscience reasoning are dominant frameworks in early childhood education and care (ECEC) worldwide. Popular since the 1960s, HCT has provided an economic understanding of human beings and offered strategies to manage the population with the promise of bringing improvements to nations. Neuroscience…

  11. Human Resources Center: An Innovation in Education; General Job Functions (Unofficial); General Plan for Curriculum Organization; Early Childhood Education.

    ERIC Educational Resources Information Center

    Pontiac City School District, MI.

    The Human Resources Center in Pontiac, Michigan is an educational institution designed to help develop talents and human potential from early childhood through adulthood. The Center offers a new approach to the problems of urban communities through comprehensive planning; education is made to serve a broader role than it has in the past.…

  12. P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating

    PubMed Central

    Inoue, Haruhisa; Higuchi, Makoto; Takao, Keizo; Tsukita, Kayoko; Karatsu, Yoshiko; Iwamoto, Yumiko; Miyakawa, Tsuyoshi; Suhara, Tetsuya; Trojanowski, John Q.; Lee, Virginia M. -Y.; Takahashi, Ryosuke

    2011-01-01

    Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand the relationship between tau pathology and behavioral impairments, we comprehensively assessed behavioral abnormalities in a mouse tauopathy model expressing the human P301S mutant tau protein in the early stage of disease to detect its initial neurological manifestations. Behavioral abnormalities, shown by open field test, elevated plus-maze test, hot plate test, Y-maze test, Barnes maze test, Morris water maze test, and/or contextual fear conditioning test, recapitulated the neurological deficits of human tauopathies with dementia. Furthermore, we discovered that prepulse inhibition (PPI), a marker of sensorimotor gating, was enhanced in these animals concomitantly with initial neuropathological changes in associated brain regions. This finding provides evidence that our tauopathy mouse model displays neurofunctional abnormalities in prodromal stages of disease, since enhancement of PPI is characteristic of amnestic mild cognitive impairment, a transitional stage between normal aging and dementia such as Alzheimer's disease (AD), in contrast with attenuated PPI in AD patients. Therefore, assessment of sensorimotor gating could be used to detect the earliest manifestations of tauopathies exemplified by prodromal AD, in which abnormal tau protein may play critical roles in the onset of neuronal dysfunctions. PMID:21698260

  13. Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells.

    PubMed

    Lin, Shu; Yuan, Zuo-Fei; Han, Yumiao; Marchione, Dylan M; Garcia, Benjamin A

    2016-07-15

    How histone post-translational modifications (PTMs) are inherited through the cell cycle remains poorly understood. Canonical histones are made in the S phase of the cell cycle. Combining mass spectrometry-based technologies and stable isotope labeling by amino acids in cell culture, we question the distribution of multiple histone PTMs on old versus new histones in synchronized human cells. We show that histone PTMs can be grouped into three categories according to their distributions. Most lysine mono-methylation and acetylation PTMs are either symmetrically distributed on old and new histones or are enriched on new histones. In contrast, most di- and tri-methylation PTMs are enriched on old histones, suggesting that the inheritance of different PTMs is regulated distinctly. Intriguingly, old and new histones are distinct in their phosphorylation status during early mitosis in the following three human cell types: HeLa, 293T, and human foreskin fibroblast cells. The mitotic hallmark H3S10ph is predominantly associated with old H3 at early mitosis and becomes symmetric with the progression of mitosis. This same distribution was observed with other mitotic phosphorylation marks, including H3T3/T6ph, H3.1/2S28ph, and H1.4S26ph but not S28/S31ph on the H3 variant H3.3. Although H3S10ph often associates with the neighboring Lys-9 di- or tri-methylations, they are not required for the asymmetric distribution of Ser-10 phosphorylation on the same H3 tail. Inhibition of the kinase Aurora B does not change the distribution despite significant reduction of H3S10ph levels. However, K9me2 abundance on the new H3 is significantly reduced after Aurora B inhibition, suggesting a cross-talk between H3S10ph and H3K9me2. PMID:27226594

  14. Actin phylogeny identifies Mesostigma viride as a flagellate ancestor of the land plants.

    PubMed

    Bhattacharya, D; Weber, K; An, S S; Berning-Koch, W

    1998-11-01

    Green algae and land plants trace their evolutionary history to a unique common ancestor. This "green lineage" is phylogenetically subdivided into two distinct assemblages, the Chlorophyta and the Streptophyta. The Chlorophyta includes the Chlorophyceae, Trebouxiophyceae, Ulvophyceae, and Prasinopohyceae, whereas the Streptophyta includes the Charophyceae plus the bryophytes, ferns, and all other multicellular land plants (Embryophyta). The Prasinophyceae is believed to contain the earliest divergences within the green lineage. Phylogenetic analyses using rDNA sequences identify the prasinophytes as a paraphyletic taxon that diverges at the base of the Chlorophyta. rDNA analyses, however, provide ambiguous results regarding the identity of the flagellate ancestor of the Streptophyta. We have sequenced the actin-encoding cDNAs from Scherffelia dubia (Prasinophyceae), Coleochaete scutata, Spirogyra sp. (Charophyceae), and the single-copy actin gene from Mesostigma viride (Prasinophyceae). Phylogenetic analyses show Mesostigma to be the earliest divergence within the Streptophyta and provide direct evidence for a scaly, biflagellate, unicellular ancestor for this lineage. This result is supported by the existence of two conserved actin-coding region introns (positions 20-3, 152-1), and one intron in the 5'-untranslated region of the actin gene shared by Mesostigma and the embryophytes.

  15. The Common Ancestor of Archaea and Eukarya Was Not an Archaeon

    PubMed Central

    Forterre, Patrick

    2013-01-01

    It is often assumed that eukarya originated from archaea. This view has been recently supported by phylogenetic analyses in which eukarya are nested within archaea. Here, I argue that these analyses are not reliable, and I critically discuss archaeal ancestor scenarios, as well as fusion scenarios for the origin of eukaryotes. Based on recognized evolutionary trends toward reduction in archaea and toward complexity in eukarya, I suggest that their last common ancestor was more complex than modern archaea but simpler than modern eukaryotes (the bug in-between scenario). I propose that the ancestors of archaea (and bacteria) escaped protoeukaryotic predators by invading high temperature biotopes, triggering their reductive evolution toward the “prokaryotic” phenotype (the thermoreduction hypothesis). Intriguingly, whereas archaea and eukarya share many basic features at the molecular level, the archaeal mobilome resembles more the bacterial than the eukaryotic one. I suggest that selection of different parts of the ancestral virosphere at the onset of the three domains played a critical role in shaping their respective biology. Eukarya probably evolved toward complexity with the help of retroviruses and large DNA viruses, whereas similar selection pressure (thermoreduction) could explain why the archaeal and bacterial mobilomes somehow resemble each other. PMID:24348094

  16. Heterokont Predator Develorapax marinus gen. et sp. nov. – A Model of the Ochrophyte Ancestor

    PubMed Central

    Aleoshin, Vladimir V.; Mylnikov, Alexander P.; Mirzaeva, Gulnara S.; Mikhailov, Kirill V.; Karpov, Sergey A.

    2016-01-01

    Heterotrophic lineages of Heterokonta (or stramenopiles), in contrast to a single monophyletic group of autotrophs, Ochrophyta, form several clades that independently branch off the heterokont stem lineage. The nearest neighbors of Ochrophyta in the phylogenetic tree appear to be almost exclusively bacterivorous, whereas the hypothesis of plastid acquisition by the ancestors of the ochrophyte lineage suggests an ability to engulf eukaryotic alga. In line with this hypothesis, the heterotrophic predator at the base of the ochrophyte lineage may be regarded as a model for the ochrophyte ancestor. Here, we present a new genus and species of marine free-living heterotrophic heterokont Develorapax marinus, which falls into an isolated heterokont cluster, along with the marine flagellate Developayella elegans, and is able to engulf eukaryotic cells. Together with environmental sequences D. marinus and D. elegans form a class-level clade Developea nom. nov. represented by species adapted to different environmental conditions and with a wide geographical distribution. The position of Developea among Heterokonta in large-scale phylogenetic tree is discussed. We propose that members of the Developea clade represent a model for transition from bacterivory to a predatory feeding mode by selection for larger prey. Presumably, such transition in the grazing strategy is possible in the presence of bacterial biofilms or aggregates expected in eutrophic environment, and has likely occurred in the ochrophyte ancestor. PMID:27536283

  17. The common ancestor of archaea and eukarya was not an archaeon.

    PubMed

    Forterre, Patrick

    2013-01-01

    It is often assumed that eukarya originated from archaea. This view has been recently supported by phylogenetic analyses in which eukarya are nested within archaea. Here, I argue that these analyses are not reliable, and I critically discuss archaeal ancestor scenarios, as well as fusion scenarios for the origin of eukaryotes. Based on recognized evolutionary trends toward reduction in archaea and toward complexity in eukarya, I suggest that their last common ancestor was more complex than modern archaea but simpler than modern eukaryotes (the bug in-between scenario). I propose that the ancestors of archaea (and bacteria) escaped protoeukaryotic predators by invading high temperature biotopes, triggering their reductive evolution toward the "prokaryotic" phenotype (the thermoreduction hypothesis). Intriguingly, whereas archaea and eukarya share many basic features at the molecular level, the archaeal mobilome resembles more the bacterial than the eukaryotic one. I suggest that selection of different parts of the ancestral virosphere at the onset of the three domains played a critical role in shaping their respective biology. Eukarya probably evolved toward complexity with the help of retroviruses and large DNA viruses, whereas similar selection pressure (thermoreduction) could explain why the archaeal and bacterial mobilomes somehow resemble each other.

  18. Heterokont Predator Develorapax marinus gen. et sp. nov. - A Model of the Ochrophyte Ancestor.

    PubMed

    Aleoshin, Vladimir V; Mylnikov, Alexander P; Mirzaeva, Gulnara S; Mikhailov, Kirill V; Karpov, Sergey A

    2016-01-01

    Heterotrophic lineages of Heterokonta (or stramenopiles), in contrast to a single monophyletic group of autotrophs, Ochrophyta, form several clades that independently branch off the heterokont stem lineage. The nearest neighbors of Ochrophyta in the phylogenetic tree appear to be almost exclusively bacterivorous, whereas the hypothesis of plastid acquisition by the ancestors of the ochrophyte lineage suggests an ability to engulf eukaryotic alga. In line with this hypothesis, the heterotrophic predator at the base of the ochrophyte lineage may be regarded as a model for the ochrophyte ancestor. Here, we present a new genus and species of marine free-living heterotrophic heterokont Develorapax marinus, which falls into an isolated heterokont cluster, along with the marine flagellate Developayella elegans, and is able to engulf eukaryotic cells. Together with environmental sequences D. marinus and D. elegans form a class-level clade Developea nom. nov. represented by species adapted to different environmental conditions and with a wide geographical distribution. The position of Developea among Heterokonta in large-scale phylogenetic tree is discussed. We propose that members of the Developea clade represent a model for transition from bacterivory to a predatory feeding mode by selection for larger prey. Presumably, such transition in the grazing strategy is possible in the presence of bacterial biofilms or aggregates expected in eutrophic environment, and has likely occurred in the ochrophyte ancestor. PMID:27536283

  19. Early afterdepolarizations promote transmural reentry in ischemic human ventricles with reduced repolarization reserve

    PubMed Central

    Dutta, Sara; Mincholé, Ana; Zacur, Ernesto; Quinn, T. Alexander; Taggart, Peter; Rodriguez, Blanca

    2016-01-01

    Aims Acute ischemia is a major cause of sudden arrhythmic death, further promoted by potassium current blockers. Macro-reentry around the ischemic region and early afterdepolarizations (EADs) caused by electrotonic current have been suggested as potential mechanisms in animal and isolated cell studies. However, ventricular and human-specific arrhythmia mechanisms and their modulation by repolarization reserve remain unclear. The goal of this paper is to unravel multiscale mechanisms underlying the modulation of arrhythmic risk by potassium current (IKr) block in human ventricles with acute regional ischemia. Methods and results A human ventricular biophysically-detailed model, with acute regional ischemia is constructed by integrating experimental knowledge on the electrophysiological ionic alterations caused by coronary occlusion. Arrhythmic risk is evaluated by determining the vulnerable window (VW) for reentry following ectopy at the ischemic border zone. Macro-reentry around the ischemic region is the main reentrant mechanism in the ischemic human ventricle with increased repolarization reserve due to the ATP-sensitive potassium current (IK(ATP)) activation. Prolongation of refractoriness by 4% caused by 30% IKr reduction counteracts the establishment of macro-reentry and reduces the VW for reentry (by 23.5%). However, a further decrease in repolarization reserve (50% IKr reduction) is less anti-arrhythmic despite further prolongation of refractoriness. This is due to the establishment of transmural reentry enabled by electrotonically-triggered EADs in the ischemic border zone. EADs are produced by L-type calcium current (ICaL) reactivation due to prolonged low amplitude electrotonic current injected during the repolarization phase. Conclusions Electrotonically-triggered EADs are identified as a potential mechanism facilitating intramural reentry in a regionally-ischemic human ventricles model with reduced repolarization reserve. PMID:26850675

  20. Ghrelin receptors in human gastrointestinal tract during prenatal and early postnatal development.

    PubMed

    Mitrović, Olivera; Čokić, Vladan; Đikić, Dragoslava; Budeč, Mirela; Vignjević, Sanja; Subotički, Tijana; Diklić, Miloš; Ajtić, Rastko

    2014-07-01

    The aim of our study was to investigate the appearance, density and distribution of ghrelin cells and GHS-R1a and GHS-R1b in the human stomach and duodenum during prenatal and early postnatal development. We examined chromogranin-A and ghrelin cells in duodenum, and GHS-R1a and GHS-R1b expression in stomach and duodenum by immunohistochemistry in embryos, fetuses, and infants. Chromogranin-A and ghrelin cells were identified in the duodenum at weeks 10 and 11 of gestation. Ghrelin cells were detected individually or clustered within the base of duodenal crypts and villi during the first trimester, while they were presented separately within the basal and apical parts of crypts and villi during the second and third trimesters. Ghrelin cells were the most numerous during the first (∼11%) and third (∼10%) trimesters of gestation development. GHS-R1a and GHS-R1b were detected at 11 and 16 weeks of gestation, showed the highest level of expression in Brunner's gland and in lower parts of duodenal crypts and villi during the second trimester in antrum, and during the third trimester in corpus and duodenum. Our findings demonstrated for the first time abundant duodenal expression of ghrelin cells and ghrelin receptors during human prenatal development indicating a role of ghrelin in the regulation of growth and differentiation of human gastrointestinal tract.

  1. Early variability in the conceptualisation of "sustainable development and human factors".

    PubMed

    Thatcher, Andrew

    2012-01-01

    The sub-discipline of "sustainable development and human factors" is relatively new, first being used in 2006 with a Technical Committee of the IEA being established only in 2009 and a similar special interest group on "green ergonomics" at the Institute of Ergonomics and Human Factors being established in 2010. In general though, the definitions and practice of "sustainable development" is highly contentious and ambiguous across a range of disciplines. This paper examines the diversity of definitions and approaches to sustainable development and human factors in the early papers in this sub-discipline. An examination of 45 chapters and papers (from 2008 to 2011) reveals a surprising consistency in the definitions used for sustainable development but also a large proportion of the papers where no definitions are given at all. The majority of papers were, however, biased towards an economic capital and social capital emphasis, which is to be expected of work traditionally in the ergonomics paradigm. Further, most papers were theoretical in nature demonstrating a great opportunity for empirical work. The variability in definitions is discussed in relation to the future challenges facing the growth of this emergent sub-discipline and opportunities for further theoretical and empirical work. PMID:22317317

  2. Validation of Early Human Dose Prediction: A Key Metric for Compound Progression in Drug Discovery.

    PubMed

    Page, Ken M

    2016-02-01

    Human dose prediction is increasingly recognized as an important parameter in Drug Discovery. Validation of a method using only in vitro and predicted parameters incorporated into a PK model was undertaken by predicting human dose and free Cmax for a number of marketed drugs and AZ Development compounds. Doses were compared to those most relevant to marketed drugs or to clinically administered doses of AZ compounds normalized either to predicted Cmin or Cmax values. Average (AFE) and absolute average (AAFE) fold-error analysis showed that best predictions were obtained using a QSAR model as the source of Vss, with Fabs set to 1 for acids and 0.5 for all other ion classes; for clearance prediction no binding correction to the well stirred model (WSM) was used for bases, while it was set to Fup/Fup(0.5) for all other ion classes. Using this combination of methods, predicted doses for 45 to 68% of the Cmin- and Cmax-normalized and marketed drug data sets were within 3-fold of the observed values, while 82 to 92% of these data sets were within 10-fold. This method for early human dose prediction is able to rank, identify, and flag risks or optimization opportunities for future development compounds within 10 days of first synthesis. PMID:26696327

  3. Human swine influenza A [H1N1]: practical advice for clinicians early in the pandemic.

    PubMed

    Fitzgerald, Dominic A

    2009-09-01

    The influenza pandemic the world was waiting for may have arrived, but the early indications are that the first wave of human swine influenza A [H1N1], also referred to as H1N1 Mexico 09 or "swine flu", is highly transmissible but of no greater virulence than seasonal influenza to date. The new swine flu H1N1 virus is a mixture of avian, porcine and human influenza RNA. With twenty thousand confirmed cases worldwide and 117 deaths within 7 weeks of the first acknowledgement of a possible pandemic by Mexican and WHO experts, the mortality rate is less than 0.1% and the majority of deaths centred upon the origin of the epidemic in Mexico [83%]. Swine flu is thus far a relatively mild illness seen predominantly in those who are healthy and under 25 years of age, perhaps reflecting protection from previous human influenza exposure in older people. As the virus spreads internationally, border protection issues have surfaced and public health initiatives are being progressively rolled out to minimise the transmission. Vaccines are being developed which will be trialled in the coming months with a likely availability by August 2009, in time for the northern hemisphere autumn and winter. Vigilance without alarm appears to be the recommendation so far.

  4. Early variability in the conceptualisation of "sustainable development and human factors".

    PubMed

    Thatcher, Andrew

    2012-01-01

    The sub-discipline of "sustainable development and human factors" is relatively new, first being used in 2006 with a Technical Committee of the IEA being established only in 2009 and a similar special interest group on "green ergonomics" at the Institute of Ergonomics and Human Factors being established in 2010. In general though, the definitions and practice of "sustainable development" is highly contentious and ambiguous across a range of disciplines. This paper examines the diversity of definitions and approaches to sustainable development and human factors in the early papers in this sub-discipline. An examination of 45 chapters and papers (from 2008 to 2011) reveals a surprising consistency in the definitions used for sustainable development but also a large proportion of the papers where no definitions are given at all. The majority of papers were, however, biased towards an economic capital and social capital emphasis, which is to be expected of work traditionally in the ergonomics paradigm. Further, most papers were theoretical in nature demonstrating a great opportunity for empirical work. The variability in definitions is discussed in relation to the future challenges facing the growth of this emergent sub-discipline and opportunities for further theoretical and empirical work.

  5. Proactive Integration of Planetary Protection Needs Into Early Design Phases of Human Exploration Missions

    NASA Astrophysics Data System (ADS)

    Race, Margaret; Conley, Catharine

    yet been developed. Looking ahead, it is recognized that these planetary protection policies will apply to both governmental and non-governmental entities for the more than 100 countries that are signatories to the Outer SpaceTreaty. Fortunately, planetary protection controls for human missions are supportive of many other important mission needs, such as maximizing closed-loop and recycling capabilities to minimize mass required, minimizing exposure of humans to planetary materials for multiple health reasons, and minimizing contamination of planetary samples and environments during exploration and science activities. Currently, there is progress on a number of fronts in translating the basic COSPAR PP Principles and Implementation Guidelines into information that links with early engineering and process considerations. For example, an IAA Study Group on Planetary Protection and Human Missions is engaging robotic and human mission developers and scientists in exploring detailed technical, engineering and operational approaches by which planetary protection objectives can be accomplished for human missions in synergism with robotic exploration and in view of other constraints. This on-going study aims to highlight important information for the early stages of planning, and identify key research and technology development (R&TD) areas for further consideration and work. Such R&TD challenges provide opportunities for individuals, institutions and agencies of emerging countries to be involved in international exploration efforts. In January 2014, the study group presented an Interim Report to the IAA Heads of Agencies Summit in Washington DC. Subsequently, the group has continued to work on expanding the initial technical recommendations and findings, focusing especially on information useful to mission architects and designers as they integrate PP considerations in their varied plans-- scientific, commercial and otherwise. Already the findings and recommendations

  6. Dynamic expression of calretinin in embryonic and early fetal human cortex

    PubMed Central

    González-Gómez, Miriam; Meyer, Gundela

    2014-01-01

    Calretinin (CR) is one of the earliest neurochemical markers in human corticogenesis. In embryos from Carnegie stages (CS) 17 to 23, calbindin (CB) and CR stain opposite poles of the incipient cortex suggesting early regionalization: CB marks the neuroepithelium of the medial boundary of the cortex with the choroid plexus (cortical hem). By contrast, CR is confined to the subventricular zone (SVZ) of the lateral and caudal ganglionic eminences at the pallial-subpallial boundary (PSB, or antihem), from where CR+/Tbr1- neurons migrate toward piriform cortex and amygdala as a component of the lateral cortical stream. At CS 19, columns of CR+ cells arise in the rostral cortex, and contribute at CS 20 to the “monolayer” of horizontal Tbr1+/CR+ and GAD+ cells in the preplate. At CS 21, the “pioneer cortical plate” appears as a radial aggregation of CR+/Tbr1+ neurons, which cover the entire future neocortex and extend the first corticofugal axons. CR expression in early human corticogenesis is thus not restricted to interneurons, but is also present in the first excitatory projection neurons of the cortex. At CS 21/22, the cortical plate is established following a lateral to medial gradient, when Tbr1+/CR- neurons settle within the pioneer cortical plate, and thus separate superficial and deep pioneer neurons. CR+ pioneer neurons disappear shortly after the formation of the cortical plate. Reelin+ Cajal-Retzius cells begin to express CR around CS21 (7/8 PCW). At CS 21–23, the CR+ SVZ at the PSB is the source of CR+ interneurons migrating into the cortical SVZ. In turn, CB+ interneurons migrate from the subpallium into the intermediate zone following the fibers of the internal capsule. Early CR+ and CB+ interneurons thus have different origins and migratory routes. CR+ cell populations in the embryonic telencephalon take part in a complex sequence of events not analyzed so far in other mammalian species, which may represent a distinctive trait of the initial

  7. Proactive Integration of Planetary Protection Needs Into Early Design Phases of Human Exploration Missions

    NASA Astrophysics Data System (ADS)

    Race, Margaret; Conley, Catharine

    yet been developed. Looking ahead, it is recognized that these planetary protection policies will apply to both governmental and non-governmental entities for the more than 100 countries that are signatories to the Outer SpaceTreaty. Fortunately, planetary protection controls for human missions are supportive of many other important mission needs, such as maximizing closed-loop and recycling capabilities to minimize mass required, minimizing exposure of humans to planetary materials for multiple health reasons, and minimizing contamination of planetary samples and environments during exploration and science activities. Currently, there is progress on a number of fronts in translating the basic COSPAR PP Principles and Implementation Guidelines into information that links with early engineering and process considerations. For example, an IAA Study Group on Planetary Protection and Human Missions is engaging robotic and human mission developers and scientists in exploring detailed technical, engineering and operational approaches by which planetary protection objectives can be accomplished for human missions in synergism with robotic exploration and in view of other constraints. This on-going study aims to highlight important information for the early stages of planning, and identify key research and technology development (R&TD) areas for further consideration and work. Such R&TD challenges provide opportunities for individuals, institutions and agencies of emerging countries to be involved in international exploration efforts. In January 2014, the study group presented an Interim Report to the IAA Heads of Agencies Summit in Washington DC. Subsequently, the group has continued to work on expanding the initial technical recommendations and findings, focusing especially on information useful to mission architects and designers as they integrate PP considerations in their varied plans-- scientific, commercial and otherwise. Already the findings and recommendations

  8. Mitochondria, the Cell Cycle, and the Origin of Sex via a Syncytial Eukaryote Common Ancestor.

    PubMed

    Garg, Sriram G; Martin, William F

    2016-01-01

    Theories for the origin of sex traditionally start with an asexual mitosing cell and add recombination, thereby deriving meiosis from mitosis. Though sex was clearly present in the eukaryote common ancestor, the order of events linking the origin of sex and the origin of mitosis is unknown. Here, we present an evolutionary inference for the origin of sex starting with a bacterial ancestor of mitochondria in the cytosol of its archaeal host. We posit that symbiotic association led to the origin of mitochondria and gene transfer to host's genome, generating a nucleus and a dedicated translational compartment, the eukaryotic cytosol, in which-by virtue of mitochondria-metabolic energy was not limiting. Spontaneous protein aggregation (monomer polymerization) and Adenosine Tri-phosphate (ATP)-dependent macromolecular movement in the cytosol thereby became selectable, giving rise to continuous microtubule-dependent chromosome separation (reduction division). We propose that eukaryotic chromosome division arose in a filamentous, syncytial, multinucleated ancestor, in which nuclei with insufficient chromosome numbers could complement each other through mRNA in the cytosol and generate new chromosome combinations through karyogamy. A syncytial (or coenocytic, a synonym) eukaryote ancestor, or Coeca, would account for the observation that the process of eukaryotic chromosome separation is more conserved than the process of eukaryotic cell division. The first progeny of such a syncytial ancestor were likely equivalent to meiospores, released into the environment by the host's vesicle secretion machinery. The natural ability of archaea (the host) to fuse and recombine brought forth reciprocal recombination among fusing (syngamy and karyogamy) progeny-sex-in an ancestrally meiotic cell cycle, from which the simpler haploid and diploid mitotic cell cycles arose. The origin of eukaryotes was the origin of vertical lineage inheritance, and sex was required to keep vertically

  9. Mitochondria, the Cell Cycle, and the Origin of Sex via a Syncytial Eukaryote Common Ancestor.

    PubMed

    Garg, Sriram G; Martin, William F

    2016-07-02

    Theories for the origin of sex traditionally start with an asexual mitosing cell and add recombination, thereby deriving meiosis from mitosis. Though sex was clearly present in the eukaryote common ancestor, the order of events linking the origin of sex and the origin of mitosis is unknown. Here, we present an evolutionary inference for the origin of sex starting with a bacterial ancestor of mitochondria in the cytosol of its archaeal host. We posit that symbiotic association led to the origin of mitochondria and gene transfer to host's genome, generating a nucleus and a dedicated translational compartment, the eukaryotic cytosol, in which-by virtue of mitochondria-metabolic energy was not limiting. Spontaneous protein aggregation (monomer polymerization) and Adenosine Tri-phosphate (ATP)-dependent macromolecular movement in the cytosol thereby became selectable, giving rise to continuous microtubule-dependent chromosome separation (reduction division). We propose that eukaryotic chromosome division arose in a filamentous, syncytial, multinucleated ancestor, in which nuclei with insufficient chromosome numbers could complement each other through mRNA in the cytosol and generate new chromosome combinations through karyogamy. A syncytial (or coenocytic, a synonym) eukaryote ancestor, or Coeca, would account for the observation that the process of eukaryotic chromosome separation is more conserved than the process of eukaryotic cell division. The first progeny of such a syncytial ancestor were likely equivalent to meiospores, released into the environment by the host's vesicle secretion machinery. The natural ability of archaea (the host) to fuse and recombine brought forth reciprocal recombination among fusing (syngamy and karyogamy) progeny-sex-in an ancestrally meiotic cell cycle, from which the simpler haploid and diploid mitotic cell cycles arose. The origin of eukaryotes was the origin of vertical lineage inheritance, and sex was required to keep vertically

  10. How We Got Here: Evolutionary Changes in Skull Shape in Humans & Their Ancestors

    ERIC Educational Resources Information Center

    Price, Rebecca M.

    2012-01-01

    This activity uses inquiry to investigate how large changes in shape can evolve from small changes in the timing of development. Students measure skull shape in fetal, infant, juvenile, and adult chimpanzees and compare them to adult skulls of "Homo sapiens," "Homo erectus," and "Australopithecus afarensis." They conclude by re-interpreting their…

  11. The Current State of Early Childhood Education Programs: How Early Childhood Center Directors Manage Their Human Resources

    ERIC Educational Resources Information Center

    Arend, Lauren E.

    2010-01-01

    Purpose: Research in the field of early childhood education (ECE) demonstrated the association between skilled directors and high quality programs. Still, most state licensing requirements do not delineate the requisite knowledge or experience necessary to be an effective director. Many ECE directors advance to their position directly from the…

  12. "On the Augmented Cognition Approach to Early Warning Systems- Human System Integration NASA Experiance

    NASA Astrophysics Data System (ADS)

    Achimowicz, Jerzy; Bakowski, Rafal; Mazur, Andrzej

    2014-05-01

    The authors present results related to the implementation of augmented cognition approach to severe weather early warning systems in aviation and aerospace operational environment. The limitations of automation and adaptive approach in severe weather warning systems are discussed. Also the positive impact of HSI (Human System Integration) NASA approach will be shown, in the process of pilot training in minimal weather conditions. The flight safety procedures related to weather conditions will be analyzed and the meteorological general aviation weather support product developed at IMGW will be presented. Special emphasis will be put on the integration of the military and civilian weather radar/lighting detection systems and the impact of space weather on aerospace operations including the use of unmanned RPAS (Remotely Controlled Aircraf Systems). J.Z. Achimowicz is also affiliated with Flight Safety Division of Military Institute of Aviation Medicine, Warsaw, Poland.

  13. The impact of early human data on clinical development: there is time to win.

    PubMed

    Swart, Piet; Lozac'h, Frederic; Simon, Marjorie; van Duijn, Esther; Vaes, Wouter H J

    2016-06-01

    Modern accelerator mass spectrometry (AMS) methods enable the routine application of this technology in drug development. By the administration of a (14)C-labelled microdose or microtrace, pharmacokinetic (PK) data, such as mass balance, metabolite profiling, and absolute bioavailability (AB) data, can be generated easier, faster, and at lower costs. Here, we emphasize the advances and impact of this technology for pharmaceutical companies. The availability of accurate intravenous (iv) PK and human absorption, distribution, metabolism, and excretion (ADME) information, even before or during Phase I trials, can improve the clinical development plan. Moreover, applying the microtrace approach during early clinical development might impact the number of clinical pharmacology and preclinical safety pharmacology studies required, and shorten the overall drug discovery program. PMID:27046542

  14. Moral and humane: patients' libraries in early nineteenth-century American mental hospitals.

    PubMed

    Dunkel, L M

    1983-07-01

    "Moral treatment" designates a period in American psychiatry in the first half of the nineteenth century when retreats and asylums, following the example of the York Retreat in England, began to offer humane care to the mentally ill. Patients had a close and personal relationship with the hospital superintendent or the resident physician; positive behavior was rewarded and patients were expected to exercise self-control. Moral treatment was marked by a well-ordered daily routine in which patients followed a therapeutic regimen of work and leisure activities. Reading was regarded as both therapeutic and recreational, and was highly recommended. For this reason, retreats and asylums maintained book collections and considered library services an important aspect of the patients' therapeutic program. This paper examines patients' library activities in eight early nineteenth-century mental hospitals where moral treatment was practiced. PMID:6354319

  15. Improving human activity recognition and its application in early stroke diagnosis.

    PubMed

    Villar, José R; González, Silvia; Sedano, Javier; Chira, Camelia; Trejo-Gabriel-Galan, Jose M

    2015-06-01

    The development of efficient stroke-detection methods is of significant importance in today's society due to the effects and impact of stroke on health and economy worldwide. This study focuses on Human Activity Recognition (HAR), which is a key component in developing an early stroke-diagnosis tool. An overview of the proposed global approach able to discriminate normal resting from stroke-related paralysis is detailed. The main contributions include an extension of the Genetic Fuzzy Finite State Machine (GFFSM) method and a new hybrid feature selection (FS) algorithm involving Principal Component Analysis (PCA) and a voting scheme putting the cross-validation results together. Experimental results show that the proposed approach is a well-performing HAR tool that can be successfully embedded in devices.

  16. The impact of early human data on clinical development: there is time to win.

    PubMed

    Swart, Piet; Lozac'h, Frederic; Simon, Marjorie; van Duijn, Esther; Vaes, Wouter H J

    2016-06-01

    Modern accelerator mass spectrometry (AMS) methods enable the routine application of this technology in drug development. By the administration of a (14)C-labelled microdose or microtrace, pharmacokinetic (PK) data, such as mass balance, metabolite profiling, and absolute bioavailability (AB) data, can be generated easier, faster, and at lower costs. Here, we emphasize the advances and impact of this technology for pharmaceutical companies. The availability of accurate intravenous (iv) PK and human absorption, distribution, metabolism, and excretion (ADME) information, even before or during Phase I trials, can improve the clinical development plan. Moreover, applying the microtrace approach during early clinical development might impact the number of clinical pharmacology and preclinical safety pharmacology studies required, and shorten the overall drug discovery program.

  17. Woodworking activities by early humans: a plant residue analysis on Acheulian stone tools from Peninj (Tanzania).

    PubMed

    Dominguez- Rodrigo, M; Serrallonga, J; Juan-Tresserras, J; Alcala, L; Luque, L

    2001-04-01

    The emergence of the Acheulian stone tool industry, between 1.7 and 1.5 m.y.a., constitutes one of the earliest evidences of complex behavior in the process of human evolution. The major technological breakthrough with the Acheulian industry was the beginning of the manufacture of bifacially shaped heavy-duty tools. Handaxes made with a predetermined form and a high degree of symmetry are the main characteristic of the Acheulian tradition. The tools are shaped through a long knapping sequence with a remarkable increase in the technical skills of the makers, compared with the older Oldowan tradition, implying a high degree of planning and foresight. Until recently, the function of these early bifacial tools remained unknown. A large number of these artefacts were found at Peninj in Tanzania, and phytolith analyses on handaxes have yielded for the first time unambiguous evidence of their function as woodworking tools.

  18. The scent of disease: human body odor contains an early chemosensory cue of sickness.

    PubMed

    Olsson, Mats J; Lundström, Johan N; Kimball, Bruce A; Gordon, Amy R; Karshikoff, Bianka; Hosseini, Nishteman; Sorjonen, Kimmo; Olgart Höglund, Caroline; Solares, Carmen; Soop, Anne; Axelsson, John; Lekander, Mats

    2014-03-01

    Observational studies have suggested that with time, some diseases result in a characteristic odor emanating from different sources on the body of a sick individual. Evolutionarily, however, it would be more advantageous if the innate immune response were detectable by healthy individuals as a first line of defense against infection by various pathogens, to optimize avoidance of contagion. We activated the innate immune system in healthy individuals by injecting them with endotoxin (lipopolysaccharide). Within just a few hours, endotoxin-exposed individuals had a more aversive body odor relative to when they were exposed to a placebo. Moreover, this effect was statistically mediated by the individuals' level of immune activation. This chemosensory detection of the early innate immune response in humans represents the first experimental evidence that disease smells and supports the notion of a "behavioral immune response" that protects healthy individuals from sick ones by altering patterns of interpersonal contact.

  19. Early events of human T lymphocyte activation are associated with type I protein kinase A activity.

    PubMed Central

    Laxminarayana, D; Berrada, A; Kammer, G M

    1993-01-01

    Human T lymphocytes possess both the type I and II isozymes of protein kinase A (PKA). The type I (PKA-I) isozyme is predominantly associated with the plasma membrane, whereas the type II (PKA-II) isozyme is primarily localized to the cytosol. Because the functions of both PKA-I and PKA-II isozymes in the biochemical events of T lymphocyte activation have not been clearly elucidated, we tested the hypothesis that very early events of normal human T lymphocyte activation are mediated by the PKA-I and/or PKA-II isozyme(s). Fresh normal human T cells and a normal human CD4+ T cell line (GK606) activated with anti-CD3-epsilon and recombinant interleukin 1 alpha (rIL-1 alpha) exhibited a peak six- to sevenfold increase of PKA phosphotransferase activity at 5 min that returned to baseline by 60 min. Similarly, both fresh T cells and the T cell line activated by phorbol myristate acetate and ionomycin demonstrated a peak eightfold increase of PKA activity by 15 min that returned toward baseline by 60 min. Chromatographic separation of the PKA isozymes and quantification of phosphotransferase activities after T cell activation by either agonist pair showed preferential activation of the PKA-I isozyme, resulting in a significant reduction in the ratio of PKA-I to PKA-II isozyme activity from 3.1:1-6.2:1 to 1.1:1-3.2:1. PKA-I isozyme activation resulted in the release of free catalytic (C) subunit, an increase in C subunit phosphotransferase activity, and the phosphorylation of T cell plasma membrane-associated proteins, p14, p17, p20, p21, p38, and p48. However, activation of the PKA-I isozyme did not appear to be required for the transcription of IL-2 mRNA, an event necessary for mitosis. These data indicate that ligand-induced T cell activation is associated with rapid activation of the PKA-I, but not PKA-II, isozyme that results in phosphorylation of plasma membrane-associated proteins. The involvement of the PKA-I isozyme during the very early events of T cell

  20. Single-cell analysis delineates a trajectory toward the human early otic lineage.

    PubMed

    Ealy, Megan; Ellwanger, Daniel C; Kosaric, Nina; Stapper, Andres P; Heller, Stefan

    2016-07-26

    Efficient pluripotent stem cell guidance protocols for the production of human posterior cranial placodes such as the otic placode that gives rise to the inner ear do not exist. Here we use a systematic approach including defined monolayer culture, signaling modulation, and single-cell gene expression analysis to delineate a developmental trajectory for human otic lineage specification in vitro. We found that modulation of bone morphogenetic protein (BMP) and WNT signaling combined with FGF and retinoic acid treatments over the course of 18 days generates cell populations that develop chronological expression of marker genes of non-neural ectoderm, preplacodal ectoderm, and early otic lineage. Gene expression along this differentiation path is distinct from other lineages such as endoderm, mesendoderm, and neural ectoderm. Single-cell analysis exposed the heterogeneity of differentiating cells and allowed discrimination of non-neural ectoderm and otic lineage cells from off-target populations. Pseudotemporal ordering of human embryonic stem cell and induced pluripotent stem cell-derived single-cell gene expression profiles revealed an initially synchronous guidance toward non-neural ectoderm, followed by comparatively asynchronous occurrences of preplacodal and otic marker genes. Positive correlation of marker gene expression between both cell lines and resemblance to mouse embryonic day 10.5 otocyst cells implied reasonable robustness of the guidance protocol. Single-cell trajectory analysis further revealed that otic progenitor cell types are induced in monolayer cultures, but further development appears impeded, likely because of lack of a lineage-stabilizing microenvironment. Our results provide a framework for future exploration of stabilizing microenvironments for efficient differentiation of stem cell-generated human otic cell types. PMID:27402757

  1. Malocclusion in Early Anatomically Modern Human: A Reflection on the Etiology of Modern Dental Misalignment

    PubMed Central

    Sarig, Rachel; Slon, Viviane; Abbas, Janan; May, Hila; Shpack, Nir; Vardimon, Alexander Dan; Hershkovitz, Israel

    2013-01-01

    Malocclusions are common in modern populations. Yet, as the study of occlusion requires an almost intact dentition in both the maxilla and mandible, searching for the ultimate cause of malocclusion is a challenge: relatively little ancient material is available for research on occlusal states. The Qafzeh 9 skull is unique, as its preserved dentition allowed us to investigate the presence and manifestations of malocclusion. The aim of this study was thus to examine the occlusal condition in the Qafzeh 9 specimen in light of modern knowledge regarding the etiology of malocclusion. We revealed a pathologic occlusion in the Qafzeh 9 skull that probably originated in the early developmental stage of the dentition, and was aggravated by forces applied by mastication. When arch continuity is interrupted due to misalignment of teeth as in this case, force transmission is not equal on both sides, causing intra-arch outcomes such as mesialization of the teeth, midline deviation, rotations and the aggravation of crowding. All are evident in the Qafzeh 9 skull: the midline deviates to the left; the incisors rotate mesio-buccally; the left segment is constricted; the left first molar is buccally positioned and the left premolars palatally tilted. The inter-arch evaluation revealed anterior cross bite with functional shift that might affect force transmission and bite force. In conclusion, the findings of the current study suggest that malocclusion of developmental origin was already present in early anatomically modern humans (AMH) (the present case being the oldest known case, dated to ca. 100,000 years); that there is no basis to the notion that early AMH had a better adjustment between teeth and jaw size; and that jaw-teeth size discrepancy could be found in prehistoric populations and is not a recent phenomenon. PMID:24278319

  2. Malocclusion in early anatomically modern human: a reflection on the etiology of modern dental misalignment.

    PubMed

    Sarig, Rachel; Slon, Viviane; Abbas, Janan; May, Hila; Shpack, Nir; Vardimon, Alexander Dan; Hershkovitz, Israel

    2013-01-01

    Malocclusions are common in modern populations. Yet, as the study of occlusion requires an almost intact dentition in both the maxilla and mandible, searching for the ultimate cause of malocclusion is a challenge: relatively little ancient material is available for research on occlusal states. The Qafzeh 9 skull is unique, as its preserved dentition allowed us to investigate the presence and manifestations of malocclusion. The aim of this study was thus to examine the occlusal condition in the Qafzeh 9 specimen in light of modern knowledge regarding the etiology of malocclusion. We revealed a pathologic occlusion in the Qafzeh 9 skull that probably originated in the early developmental stage of the dentition, and was aggravated by forces applied by mastication. When arch continuity is interrupted due to misalignment of teeth as in this case, force transmission is not equal on both sides, causing intra-arch outcomes such as mesialization of the teeth, midline deviation, rotations and the aggravation of crowding. All are evident in the Qafzeh 9 skull: the midline deviates to the left; the incisors rotate mesio-buccally; the left segment is constricted; the left first molar is buccally positioned and the left premolars palatally tilted. The inter-arch evaluation revealed anterior cross bite with functional shift that might affect force transmission and bite force. In conclusion, the findings of the current study suggest that malocclusion of developmental origin was already present in early anatomically modern humans (AMH) (the present case being the oldest known case, dated to ca. 100,000 years); that there is no basis to the notion that early AMH had a better adjustment between teeth and jaw size; and that jaw-teeth size discrepancy could be found in prehistoric populations and is not a recent phenomenon.

  3. The influence of early embryo traits on human embryonic stem cell derivation efficiency.

    PubMed

    O'Leary, Thomas; Heindryckx, Björn; Lierman, Sylvie; Van der Jeught, Margot; Menten, Björn; Deforce, Dieter; Cornelissen, Ria; de Sousa Lopes, Susana Chuva; De Sutter, Petra

    2011-05-01

    Despite its prognostic value in in vitro fertilization, early embryo morphology is not reported on in the derivation of human embryonic stem cell (hESC) lines. Standard hESC derivation does rely on blastocyst development and its efficiency is highly correlated to inner cell mass (ICM) quality. Poor-quality embryos (PQEs) donated for hESC derivation may have a range of cleavage-stage abnormalities that are known to compromise further development. This study was implemented to determine whether specific PQEs traits influence the efficiency of good-quality ICMs to derive new hESC lines. We found that although the types of PQEs investigated were all able to make blastocysts with good-quality ICMs, the ICMs were unequal in their ability to derive hESCs. Good-quality ICMs from embryos with multiple poor-quality traits were unable to generate hESC lines, in contrast to good-quality ICMs from embryos with a single poor-quality trait. In addition, our data suggest a direct correlation between the number of ICM cells present in the blastocyst and its capacity to derive new hESC lines. This study is the first to demonstrate that ICM quality alone is an incomplete indicator of hESC derivation and that application of in vitro fertilization-based early embryo scoring can help predict hESC derivation efficiency. Experiments aiming to quantify, improve upon, or compare hESC derivation efficiency should thus take into consideration early embryo morphology scoring for the comparison of groups with equal developmental competence.

  4. Global Phosphoproteomic Mapping of Early Mitotic Exit in Human Cells Identifies Novel Substrate Dephosphorylation Motifs.

    PubMed

    McCloy, Rachael A; Parker, Benjamin L; Rogers, Samuel; Chaudhuri, Rima; Gayevskiy, Velimir; Hoffman, Nolan J; Ali, Naveid; Watkins, D Neil; Daly, Roger J; James, David E; Lorca, Thierry; Castro, Anna; Burgess, Andrew

    2015-08-01

    Entry into mitosis is driven by the coordinated phosphorylation of thousands of proteins. For the cell to complete mitosis and divide into two identical daughter cells it must regulate dephosphorylation of these proteins in a highly ordered, temporal manner. There is currently a lack of a complete understanding of the phosphorylation changes that occur during the initial stages of mitotic exit in human cells. Therefore, we performed a large unbiased, global analysis to map the very first dephosphorylation events that occur as cells exit mitosis. We identified and quantified the modification of >16,000 phosphosites on >3300 unique proteins during early mitotic exit, providing up to eightfold greater resolution than previous studies. The data have been deposited to the ProteomeXchange with identifier PXD001559. Only a small fraction (∼ 10%) of phosphorylation sites were dephosphorylated during early mitotic exit and these occurred on proteins involved in critical early exit events, including organization of the mitotic spindle, the spindle assembly checkpoint, and reformation of the nuclear envelope. Surprisingly this enrichment was observed across all kinase consensus motifs, indicating that it is independent of the upstream phosphorylating kinase. Therefore, dephosphorylation of these sites is likely determined by the specificity of phosphatase/s rather than the activity of kinase/s. Dephosphorylation was significantly affected by the amino acids at and surrounding the phosphorylation site, with several unique evolutionarily conserved amino acids correlating strongly with phosphorylation status. These data provide a potential mechanism for the specificity of phosphatases, and how they co-ordinate the ordered events of mitotic exit. In summary, our results provide a global overview of the phosphorylation changes that occur during the very first stages of mitotic exit, providing novel mechanistic insight into how phosphatase/s specifically regulate this critical

  5. The cult of amphioxus in German Darwinism; or, our gelatinous ancestors in Naples' blue and balmy bay.

    PubMed

    Hopwood, Nick

    2015-01-01

    Biologists having rediscovered amphioxus, also known as the lancelet or Branchiostoma, it is time to reassess its place in early Darwinist debates over vertebrate origins. While the advent of the ascidian-amphioxus theory and challenges from various competitors have been, documented, this article offers a richer account of the public appeal of amphioxus as a primitive ancestor. The focus is on how the 'German Darwin' Ernst Haeckel persuaded general magazine and newspaper readers to revere this "flesh of our flesh and blood of our blood", and especially on Das neue Laienbrevier des Haeckelismus (The new lay breviary of Haeckelism) by Moritz Reymond with cartoons by Fritz Steub. From the late 1870s these successful little books of verse introduced the Neapolitan discoveries that made the animal's name and satirized Haeckel's rise as high priest of its cult. One song is reproduced and translated here, with a contemporary "imitation" by the Canadian palaeontologist Edward John Chapman, and extracts from others. Predating the American "It's a long way from amphioxus" by decades, these rhymes dramatize neglected 'species politics' of Darwinism and highlight the roles of humour in negotiating evolution.

  6. The cult of amphioxus in German Darwinism; or, our gelatinous ancestors in Naples' blue and balmy bay.

    PubMed

    Hopwood, Nick

    2015-01-01

    Biologists having rediscovered amphioxus, also known as the lancelet or Branchiostoma, it is time to reassess its place in early Darwinist debates over vertebrate origins. While the advent of the ascidian-amphioxus theory and challenges from various competitors have been, documented, this article offers a richer account of the public appeal of amphioxus as a primitive ancestor. The focus is on how the 'German Darwin' Ernst Haeckel persuaded general magazine and newspaper readers to revere this "flesh of our flesh and blood of our blood", and especially on Das neue Laienbrevier des Haeckelismus (The new lay breviary of Haeckelism) by Moritz Reymond with cartoons by Fritz Steub. From the late 1870s these successful little books of verse introduced the Neapolitan discoveries that made the animal's name and satirized Haeckel's rise as high priest of its cult. One song is reproduced and translated here, with a contemporary "imitation" by the Canadian palaeontologist Edward John Chapman, and extracts from others. Predating the American "It's a long way from amphioxus" by decades, these rhymes dramatize neglected 'species politics' of Darwinism and highlight the roles of humour in negotiating evolution. PMID:26013195

  7. Early-stage development of human induced pluripotent stem cell-derived neurons.

    PubMed

    Ohara, Yuki; Koganezawa, Noriko; Yamazaki, Hiroyuki; Roppongi, Reiko T; Sato, Kaoru; Sekino, Yuko; Shirao, Tomoaki

    2015-12-01

    Recent advances in human induced pluripotent stem cells (hiPSCs) offer new possibilities for biomedical research and clinical applications. Differentiated neurons from hiPSCs are expected to be useful for developing novel methods of treatment for various neurological diseases. However, the detailed process of functional maturation of hiPSC-derived neurons (hiPS neurons) remains poorly understood. This study analyzes development of hiPS neurons, focusing specifically on early developmental stages through 48 hr after cell seeding; development was compared with that of primary cultured neurons derived from the rat hippocampus. At 5 hr after cell seeding, neurite formation occurs in a similar manner in both neuronal populations. However, very few neurons with axonal polarization were observed in the hiPS neurons even after 48 hr, indicating that hiPS neurons differentiate more slowly than rat neurons. We further investigated the elongation speed of axons and found that hiPS neuronal axons were slower. In addition, we characterized the growth cones. The localization patterns of skeletal proteins F-actin, microtubule, and drebrin were similar to those of rat neurons, and actin depolymerization by cytochalasin D induced similar changes in cytoskeletal distribution in the growth cones between hiPS neurons and rat neurons. These results indicate that, during the very early developmental stage, hiPS neurons develop comparably to rat hippocampal neurons with regard to axonal differentiation, but the growth of axons is slower.

  8. Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in newborn macaques

    PubMed Central

    Hessell, Ann J.; Jaworski, J. Pablo; Epson, Erin; Matsuda, Kenta; Pandey, Shilpi; Kahl, Christoph; Reed, Jason; Sutton, William F.; Hammond, Katherine B.; Cheever, Tracy A.; Barnette, Philip T.; Legasse, Alfred W.; Planer, Shannon; Stanton, Jeffrey J.; Pegu, Amarendra; Chen, Xuejun; Wang, Keyun; Siess, Don; Burke, David; Park, Byung S.; Axthelm, Michael K.; Lewis, Anne; Hirsch, Vanessa M.; Graham, Barney S.; Mascola, John R.; Sacha, Jonah B.; Haigwood, Nancy L.

    2016-01-01

    Prevention of mother to child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested anti-HIV-1 human neutralizing monoclonal antibodies (NmAb) as post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with SHIVSF162P3. On days 1, 4, 7, and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h following administration. Replicating virus was found in multiple tissues by day 1 in animals without treatment. All NmAb-treated macaques were free of virus in blood and tissues at 6 months post-exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged following CD8+ T cell depletion. These results suggest early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs. PMID:26998834

  9. Early human speciation, brain expansion and dispersal influenced by African climate pulses.

    PubMed

    Shultz, Susanne; Maslin, Mark

    2013-01-01

    Early human evolution is characterised by pulsed speciation and dispersal events that cannot be explained fully by global or continental paleoclimate records. We propose that the collated record of ephemeral East African Rift System (EARS) lakes could be a proxy for the regional paleoclimate conditions experienced by early hominins. Here we show that the presence of these lakes is associated with low levels of dust deposition in both West African and Mediterranean records, but is not associated with long-term global cooling and aridification of East Africa. Hominin expansion and diversification seem to be associated with climate pulses characterized by the precession-forced appearance and disappearance of deep EARS lakes. The most profound period for hominin evolution occurs at about 1.9 Ma; with the highest recorded diversity of hominin species, the appearance of Homo (sensu stricto) and major dispersal events out of East Africa into Eurasia. During this period, ephemeral deep-freshwater lakes appeared along the whole length of the EARS, fundamentally changing the local environment. The relationship between the local environment and hominin brain expansion is less clear. The major step-wise expansion in brain size around 1.9 Ma when Homo appeared was coeval with the occurrence of ephemeral deep lakes. Subsequent incremental increases in brain size are associated with dry periods with few if any lakes. Plio-Pleistocene East African climate pulses as evinced by the paleo-lake records seem, therefore, fundamental to hominin speciation, encephalisation and migration.

  10. Heatwave Early Warning Systems and Adaptation Advice to Reduce Human Health Consequences of Heatwaves

    PubMed Central

    Lowe, Dianne; Ebi, Kristie L.; Forsberg, Bertil

    2011-01-01

    Introduction: With climate change, there has been an increase in the frequency, intensity and duration of heatwave events. In response to the devastating mortality and morbidity of recent heatwave events, many countries have introduced heatwave early warning systems (HEWS). HEWS are designed to reduce the avoidable human health consequences of heatwaves through timely notification of prevention measures to vulnerable populations. Objective: To identify the key characteristics of HEWS in European countries to help inform modification of current, and development of, new systems and plans. Methods: We searched the internet to identify HEWS policy or government documents for 33 European countries and requested information from relevant organizations. We translated the HEWS documents and extracted details on the trigger indicators, thresholds for action, notification strategies, message intermediaries, communication and dissemination strategies, prevention strategies recommended and specified target audiences. Findings and Conclusions: Twelve European countries have HEWS. Although there are many similarities among the HEWS, there also are differences in key characteristics that could inform improvements in heatwave early warning plans. PMID:22408593

  11. Behavior of homologous chromosomes in early meiotic stages of human spermatocytes as revealed by FISH

    SciTech Connect

    Bar-Am, I.; Avivi, L.; Mukame, E.

    1994-09-01

    The process by which homologous chromosomes recognize each other at the beginning of meiosis, prior to synapsis, is poorly understood. To gain a better understanding as to when, where and how a given chromosome approaches its pairing partner, chromosome behavior at early stages of meiosis in human spermatocytes was studied. Using multi-color FISH with centromeric- and telomeric-specific probes, as well as with whole chromosome DNA libraries, it was clearly aligned. Rather, similarly to non-homologous chromosomes, they were well separated from each other. At the commencement of synapsis, during the process of homology search, homologues underwent a drastic conformational change, elongating into strands that approached each other by their telomeres. Just preceding the co-alignment of the homologous centromeres, telomeres changed their interphase random distribution and occupied a confined region of the nuclear periphery. Following synapsis, telomeres spread over the whole nuclear periphery. These dynamics in the telomeres distribution, which are unique to early stages of meiosis, are presumably related to the role that telomeres play in the process of homology search and the commencement of synapsis.

  12. Measurement of the human esophageal cancer in an early stage with Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Maeda, Yasuhiro; Ishigaki, Mika; Taketani, Akinori; Andriana, Bibin B.; Ishihara, Ryu; Sato, Hidetoshi

    2014-02-01

    The esophageal cancer has a tendency to transfer to another part of the body and the surgical operation itself sometimes gives high risk in vital function because many delicate organs exist near the esophagus. So the esophageal cancer is a disease with a high mortality. So, in order to lead a higher survival rate five years after the cancer's treatment, the investigation of the diagnosis methods or techniques of the cancer in an early stage and support the therapy are required. In this study, we performed the ex vivo experiments to obtain the Raman spectra from normal and early-stage tumor (stage-0) human esophageal sample by using Raman spectroscopy. The Raman spectra are collected by the homemade Raman spectrometer with the wavelength of 785 nm and Raman probe with 600-um-diameter. The principal component analysis (PCA) is performed after collection of spectra to recognize which materials changed in normal part and cancerous pert. After that, the linear discriminant analysis (LDA) is performed to predict the tissue type. The result of PCA indicates that the tumor tissue is associated with a decrease in tryptophan concentration. Furthermore, we can predict the tissue type with 80% accuracy by LDA which model is made by tryptophan bands.

  13. Early Human Speciation, Brain Expansion and Dispersal Influenced by African Climate Pulses

    PubMed Central

    Shultz, Susanne; Maslin, Mark

    2013-01-01

    Early human evolution is characterised by pulsed speciation and dispersal events that cannot be explained fully by global or continental paleoclimate records. We propose that the collated record of ephemeral East African Rift System (EARS) lakes could be a proxy for the regional paleoclimate conditions experienced by early hominins. Here we show that the presence of these lakes is associated with low levels of dust deposition in both West African and Mediterranean records, but is not associated with long-term global cooling and aridification of East Africa. Hominin expansion and diversification seem to be associated with climate pulses characterized by the precession-forced appearance and disappearance of deep EARS lakes. The most profound period for hominin evolution occurs at about 1.9 Ma; with the highest recorded diversity of hominin species, the appearance of Homo (sensu stricto) and major dispersal events out of East Africa into Eurasia. During this period, ephemeral deep-freshwater lakes appeared along the whole length of the EARS, fundamentally changing the local environment. The relationship between the local environment and hominin brain expansion is less clear. The major step-wise expansion in brain size around 1.9 Ma when Homo appeared was coeval with the occurrence of ephemeral deep lakes. Subsequent incremental increases in brain size are associated with dry periods with few if any lakes. Plio-Pleistocene East African climate pulses as evinced by the paleo-lake records seem, therefore, fundamental to hominin speciation, encephalisation and migration. PMID:24146922

  14. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

    PubMed Central

    Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

    2016-01-01

    The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032

  15. The spatiotemporal hormonal orchestration of human folliculogenesis, early embryogenesis and blastocyst implantation.

    PubMed

    Atwood, Craig S; Vadakkadath Meethal, Sivan

    2016-07-15

    The early reproductive events starting with folliculogenesis and ending with blastocyst implantation into the uterine endometrium are regulated by a complex interplay among endocrine, paracrine and autocrine factors. This review examines the spatiotemporal integration of these maternal and embryonic signals that are required for successful reproduction. In coordination with hypothalamic-pituitary-gonadal (HPG) hormones, an intraovarian HPG-like axis regulates folliculogenesis, follicular quiescence, ovulation, follicular atresia, and corpus luteal functions. Upon conception and passage of the zygote through the fallopian tube, the contribution of maternal hormones in the form of paracrine secretions from the endosalpinx to embryonic development declines, with autocrine and paracrine signaling becoming increasingly important as instructional signals for the differentiation of the early zygote/morula into a blastocyst. These maternal and embryonic signals include activin and gonadotropin-releasing hormone 1 (GnRH1) that are crucial for the synthesis and secretion of the 'pregnancy' hormone human chorionic gonadotropin (hCG). hCG in turn signals pre-implantation embryonic cell division and sex steroid production required for stem cell differentiation, and subsequent blastulation, gastrulation, cavitation and blastocyst formation. Upon reaching the uterus, blastocyst hatching occurs under the influence of decreased activin signaling, while the attachment and invasion of the trophoblast into the endometrium appears to be driven by a decrease in activin signaling, and by increased GnRH1 and hCG signaling that allows for tissue remodeling and the controlled invasion of the blastocyst into the uterine endometrium. This review demonstrates the importance of integrative endocrine, paracrine, and autocrine signaling for successful human reproduction.

  16. Mitochondrial respiratory control and early defects of oxidative phosphorylation in the failing human heart.

    PubMed

    Lemieux, Hélène; Semsroth, Severin; Antretter, Herwig; Höfer, Daniel; Gnaiger, Erich

    2011-12-01

    Heart failure is a consequence of progressive deterioration of cardiac performance. Little is known about the role of impaired oxidative phosphorylation in the progression of the disease, since previous studies of mitochondrial injuries are restricted to end-stage chronic heart failure. The present study aimed at evaluating the involvement of mitochondrial dysfunction in the development of human heart failure. We measured the control of oxidative phosphorylation with high-resolution respirometry in permeabilized myocardial fibres from donor hearts (controls), and patients with no or mild heart failure but presenting with heart disease, or chronic heart failure due to dilated or ischemic cardiomyopathy. The capacity of the phosphorylation system exerted a strong limitation on oxidative phosphorylation in the human heart, estimated at 121 pmol O(2)s(-1)mg(-1) in the healthy left ventricle. In heart disease, a specific defect of the phosphorylation system, Complex I-linked respiration, and mass-specific fatty acid oxidation were identified. These early defects were also significant in chronic heart failure, where the capacities of the oxidative phosphorylation and electron transfer systems per cardiac tissue mass were decreased with all tested substrate combinations, suggesting a decline of mitochondrial density. Oxidative phosphorylation and electron transfer system capacities were higher in ventricles compared to atria, but the impaired mitochondrial quality was identical in the four cardiac chambers of chronic heart failure patients. Coupling was preserved in heart disease and chronic heart failure, in contrast to the mitochondrial dysfunction observed after prolonged cold storage of cardiac tissue. Mitochondrial defects in the phosphorylation system, Complex I respiration and mass-specific fatty acid oxidation occurred early in the development of heart failure. Targeting these mitochondrial injuries with metabolic therapy may offer a promising approach to delay

  17. The spatiotemporal hormonal orchestration of human folliculogenesis, early embryogenesis and blastocyst implantation.

    PubMed

    Atwood, Craig S; Vadakkadath Meethal, Sivan

    2016-07-15

    The early reproductive events starting with folliculogenesis and ending with blastocyst implantation into the uterine endometrium are regulated by a complex interplay among endocrine, paracrine and autocrine factors. This review examines the spatiotemporal integration of these maternal and embryonic signals that are required for successful reproduction. In coordination with hypothalamic-pituitary-gonadal (HPG) hormones, an intraovarian HPG-like axis regulates folliculogenesis, follicular quiescence, ovulation, follicular atresia, and corpus luteal functions. Upon conception and passage of the zygote through the fallopian tube, the contribution of maternal hormones in the form of paracrine secretions from the endosalpinx to embryonic development declines, with autocrine and paracrine signaling becoming increasingly important as instructional signals for the differentiation of the early zygote/morula into a blastocyst. These maternal and embryonic signals include activin and gonadotropin-releasing hormone 1 (GnRH1) that are crucial for the synthesis and secretion of the 'pregnancy' hormone human chorionic gonadotropin (hCG). hCG in turn signals pre-implantation embryonic cell division and sex steroid production required for stem cell differentiation, and subsequent blastulation, gastrulation, cavitation and blastocyst formation. Upon reaching the uterus, blastocyst hatching occurs under the influence of decreased activin signaling, while the attachment and invasion of the trophoblast into the endometrium appears to be driven by a decrease in activin signaling, and by increased GnRH1 and hCG signaling that allows for tissue remodeling and the controlled invasion of the blastocyst into the uterine endometrium. This review demonstrates the importance of integrative endocrine, paracrine, and autocrine signaling for successful human reproduction. PMID:27045358

  18. Ranging in Human Sonar: Effects of Additional Early Reflections and Exploratory Head Movements

    PubMed Central

    Wallmeier, Ludwig; Wiegrebe, Lutz

    2014-01-01

    Many blind people rely on echoes from self-produced sounds to assess their environment. It has been shown that human subjects can use echolocation for directional localization and orientation in a room, but echo-acoustic distance perception - e.g. to determine one's position in a room - has received little scientific attention, and systematic studies on the influence of additional early reflections and exploratory head movements are lacking. This study investigates echo-acoustic distance discrimination in virtual echo-acoustic space, using the impulse responses of a real corridor. Six blindfolded sighted subjects and a blind echolocation expert had to discriminate between two positions in the virtual corridor, which differed by their distance to the front wall, but not to the lateral walls. To solve this task, participants evaluated echoes that were generated in real time from self-produced vocalizations. Across experimental conditions, we systematically varied the restrictions for head rotations, the subjects' orientation in virtual space and the reference position. Three key results were observed. First, all participants successfully solved the task with discrimination thresholds below 1 m for all reference distances (0.75–4 m). Performance was best for the smallest reference distance of 0.75 m, with thresholds around 20 cm. Second, distance discrimination performance was relatively robust against additional early reflections, compared to other echolocation tasks like directional localization. Third, free head rotations during echolocation can improve distance discrimination performance in complex environmental settings. However, head movements do not necessarily provide a benefit over static echolocation from an optimal single orientation. These results show that accurate distance discrimination through echolocation is possible over a wide range of reference distances and environmental conditions. This is an important functional benefit of human echolocation

  19. Ranging in human sonar: effects of additional early reflections and exploratory head movements.

    PubMed

    Wallmeier, Ludwig; Wiegrebe, Lutz

    2014-01-01

    Many blind people rely on echoes from self-produced sounds to assess their environment. It has been shown that human subjects can use echolocation for directional localization and orientation in a room, but echo-acoustic distance perception--e.g. to determine one's position in a room--has received little scientific attention, and systematic studies on the influence of additional early reflections and exploratory head movements are lacking. This study investigates echo-acoustic distance discrimination in virtual echo-acoustic space, using the impulse responses of a real corridor. Six blindfolded sighted subjects and a blind echolocation expert had to discriminate between two positions in the virtual corridor, which differed by their distance to the front wall, but not to the lateral walls. To solve this task, participants evaluated echoes that were generated in real time from self-produced vocalizations. Across experimental conditions, we systematically varied the restrictions for head rotations, the subjects' orientation in virtual space and the reference position. Three key results were observed. First, all participants successfully solved the task with discrimination thresholds below 1 m for all reference distances (0.75-4 m). Performance was best for the smallest reference distance of 0.75 m, with thresholds around 20 cm. Second, distance discrimination performance was relatively robust against additional early reflections, compared to other echolocation tasks like directional localization. Third, free head rotations during echolocation can improve distance discrimination performance in complex environmental settings. However, head movements do not necessarily provide a benefit over static echolocation from an optimal single orientation. These results show that accurate distance discrimination through echolocation is possible over a wide range of reference distances and environmental conditions. This is an important functional benefit of human echolocation

  20. Effects of adverse early-life events on aggression and anti-social behaviours in animals and humans.

    PubMed

    Haller, J; Harold, G; Sandi, C; Neumann, I D

    2014-10-01

    We review the impact of early adversities on the development of violence and antisocial behaviour in humans, and present three aetiological animal models of escalated rodent aggression, each disentangling the consequences of one particular adverse early-life factor. A review of the human data, as well as those obtained with the animal models of repeated maternal separation, post-weaning social isolation and peripubertal stress, clearly shows that adverse developmental conditions strongly affect aggressive behaviour displayed in adulthood, the emotional responses to social challenges and the neuronal mechanisms activated by conflict. Although similarities between models are evident, important differences were also noted, demonstrating that the behavioural, emotional and neuronal consequences of early adversities are to a large extent dependent on aetiological factors. These findings support recent theories on human aggression, which suggest that particular developmental trajectories lead to specific forms of aggressive behaviour and brain dysfunctions. However, dissecting the roles of particular aetiological factors in humans is difficult because these occur in various combinations; in addition, the neuroscientific tools employed in humans still lack the depth of analysis of those used in animal research. We suggest that the analytical approach of the rodent models presented here may be successfully used to complement human findings and to develop integrative models of the complex relationship between early adversity, brain development and aggressive behaviour.

  1. Putative prethymic T cell precursors within the early human embryonic liver: a molecular and functional analysis

    PubMed Central

    1993-01-01

    Hematopoietic cells present in the liver in early human fetal life were characterized by phenotypic analysis using a broad panel of monoclonal antibodies. Expression of very late antigen 4 and leukocyte function- associated antigen 3 cell adhesion receptors and 4F2 cell activation molecules was found in all fetal liver hematopoietic cells before acquisition of T cell-, B cell-, or myeloid-specific surface markers, and before the time of intrathymic colonization. Molecular studies showed that expression of the interleukin 2 receptor beta (IL-2R beta) also occurred in the embryonic liver at this early ontogenic stage. In contrast, no expression of IL-2R alpha or IL-2 transcripts was found in fetal liver cells, whereas transcription of the IL-4 gene was detected in a small fetal liver cell subset. Putative T cell precursors were identified among the hematopoietic fetal liver cells by the expression of genes encoding the gamma, delta, epsilon, and zeta invariant chains of the CD3-T cell receptor (TCR) complex. However, no transcription of the polymorphic alpha and beta TCR genes was detected. Functional in vitro assays further demonstrated that fetal liver hematopoietic cells from those early embryos were capable of proliferating in response to T cell growth factors, including IL-4 and IL-2. However, whereas IL-4- induced proliferation paralleled the appearance in vitro of CD45+CD7- CD4dull cells expressing the CD14 myeloid antigen, as well as of CD34+ primitive hematopoietic progenitors, differentiation into CD45+CD7+CD8+CD3- immature T cells was observed when using IL-2. Moreover, coculture with thymic epithelial cell monolayers provided additional evidence that early fetal liver hematopoietic cells may include very primitive T cell precursors, which were able to differentiate in vitro into TCR alpha/beta+ mature T cells. Therefore, our results indicate that, after triggering of the T cell-specific maturation program in primitive fetal liver hematopoietic progenitors

  2. Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

    PubMed Central

    Li, Yue; Xie, Changchun; Murphy, Susan K.; Skaar, David; Nye, Monica; Vidal, Adriana C.; Cecil, Kim M.; Dietrich, Kim N.; Puga, Alvaro; Jirtle, Randy L.; Hoyo, Cathrine

    2015-01-01

    Background: Lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. Objectives: The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. Methods: Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study from birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. Results: Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = –0.0014; 95% CI: –0.0023, –0.0005, p = 0.002), stronger in males (β = –0.0024; 95% CI: –0.0038, –0.0009, p = 0.003) than in females (β = –0.0009; 95% CI: –0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = –0.0013; 95% CI: –0.0023, –0.0003, p = 0.01) DMR methylation, but primarily in females, (β = –0.0017; 95% CI: –0.0029, –0.0006, p = 0.005) rather than in males, (β = –0.0004; 95% CI: –0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from

  3. Structural basis for early-onset neurological disorders caused by mutations in human selenocysteine synthase

    PubMed Central

    Puppala, Anupama K.; French, Rachel L.; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Simonović, Miljan

    2016-01-01

    Selenocysteine synthase (SepSecS) catalyzes the terminal reaction of selenocysteine, and is vital for human selenoproteome integrity. Autosomal recessive inheritance of mutations in SepSecS–Ala239Thr, Thr325Ser, Tyr334Cys and Tyr429*–induced severe, early-onset, neurological disorders in distinct human populations. Although harboring different mutant alleles, patients presented remarkably similar phenotypes typified by cerebellar and cerebral atrophy, seizures, irritability, ataxia, and extreme spasticity. However, it has remained unclear how these genetic alterations affected the structure of SepSecS and subsequently elicited the development of a neurological pathology. Herein, our biophysical and structural characterization demonstrates that, with the exception of Tyr429*, pathogenic mutations decrease protein stability and trigger protein misfolding. We propose that the reduced stability and increased propensity towards misfolding are the main causes for the loss of SepSecS activity in afflicted patients, and that these factors contribute to disease progression. We also suggest that misfolding of enzymes regulating protein synthesis should be considered in the diagnosis and study of childhood neurological disorders. PMID:27576344

  4. Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans.

    PubMed

    Evans, Erica K; Tester, Richland; Aslanian, Sharon; Karp, Russell; Sheets, Michael; Labenski, Matthew T; Witowski, Steven R; Lounsbury, Heather; Chaturvedi, Prasoon; Mazdiyasni, Hormoz; Zhu, Zhendong; Nacht, Mariana; Freed, Martin I; Petter, Russell C; Dubrovskiy, Alex; Singh, Juswinder; Westlin, William F

    2013-08-01

    Targeted therapies that suppress B cell receptor (BCR) signaling have emerged as promising agents in autoimmune disease and B cell malignancies. Bruton's tyrosine kinase (Btk) plays a crucial role in B cell development and activation through the BCR signaling pathway and represents a new target for diseases characterized by inappropriate B cell activity. N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (CC-292) is a highly selective, covalent Btk inhibitor and a sensitive and quantitative assay that measures CC-292-Btk engagement has been developed. This translational pharmacodynamic assay has accompanied CC-292 through each step of drug discovery and development. These studies demonstrate the quantity of Btk bound by CC-292 correlates with the efficacy of CC-292 in vitro and in the collagen-induced arthritis model of autoimmune disease. Recently, CC-292 has entered human clinical trials with a trial design that has provided rapid insight into safety, pharmacokinetics, and pharmacodynamics. This first-in-human healthy volunteer trial has demonstrated that a single oral dose of 2 mg/kg CC-292 consistently engaged all circulating Btk protein and provides the basis for rational dose selection in future clinical trials. This targeted covalent drug design approach has enabled the discovery and early clinical development of CC-292 and has provided support for Btk as a valuable drug target for B-cell mediated disorders.

  5. Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI.

    PubMed

    Rubin, E M; Krauss, R M; Spangler, E A; Verstuyft, J G; Clift, S M

    1991-09-19

    Epidemiological surveys have identified a strong inverse relationship between the amount in the plasma of high density lipoproteins (HDL), apolipoprotein AI (ApoA-I), the major protein component of HDL, and the risk for atherosclerosis in humans. It is not known if this relationship arises from a direct antiatherogenic effect of these plasma components or if it is the result of other factors also associated with increases in ApoA-I and HDL levels. Because some strains of mice are susceptible to diet-induced formation of preatherosclerotic fatty streak lesions, and because of available techniques for the genetic manipulation of this organism, the murine system offers a unique setting in which to investigate the process of early atherogenesis. To test the hypothesis that induction of a high plasma concentration of ApoA-I and HDL would inhibit this process, we studied the effects of atherogenic diets on transgenic mice expressing high amounts of human ApoA-I. We report that transgenic mice with high plasma ApoA-I and HDL levels were significantly protected from the development of fatty streak lesions.

  6. Last glacial megafaunal death assemblage and early human occupation at Lake Menindee, southeastern Australia

    NASA Astrophysics Data System (ADS)

    Cupper, Matthew L.; Duncan, Jacqui

    2006-09-01

    The Tedford subfossil locality at Lake Menindee preserves a diverse assemblage of marsupials, monotremes and placental rodents. Of the 38 mammal taxa recorded at the site, almost a third are of extinct megafauna. Some of the bones are articulated or semi-articulated and include almost complete skeletons, indicating that aeolian sediments rapidly buried the animals following death. New optical ages show the site dates to the early part of the last glacial (55,700 ± 1300 yr weighted mean age). This is close to the 51,200-39,800 yr Australia-wide extinction age for megafauna suggested by Roberts et al. [2001, Science 292:1888-1892], but like all previous researchers, we cannot conclusively determine whether humans were implicated in the deaths of the animals. Although an intrusive hearth at the site dating to 45,100 ± 1400 yr ago is the oldest evidence of human occupation of the Darling River, no artifacts were identified in situ within the sub-fossil-bearing unit. Non-anthropogenic causes, such as natural senescence or ecosystem stress due to climatic aridity, probably explain the mortality of the faunal assemblage at Lake Menindee.

  7. Vestibular activation differentially modulates human early visual cortex and V5/MT excitability and response entropy.

    PubMed

    Seemungal, Barry M; Guzman-Lopez, Jessica; Arshad, Qadeer; Schultz, Simon R; Walsh, Vincent; Yousif, Nada

    2013-01-01

    Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC.

  8. Prediction model for aneuploidy in early human embryo development revealed by single-cell analysis

    PubMed Central

    Vera-Rodriguez, Maria; Chavez, Shawn L.; Rubio, Carmen; Pera, Renee A. Reijo; Simon, Carlos

    2015-01-01

    Aneuploidies are prevalent in the human embryo and impair proper development, leading to cell cycle arrest. Recent advances in imaging and molecular and genetic analyses are postulated as promising strategies to unveil the mechanisms involved in aneuploidy generation. Here we combine time-lapse, complete chromosomal assessment and single-cell RT–qPCR to simultaneously obtain information from all cells that compose a human embryo until the approximately eight-cell stage (n=85). Our data indicate that the chromosomal status of aneuploid embryos (n=26), including those that are mosaic (n=3), correlates with significant differences in the duration of the first mitotic phase when compared with euploid embryos (n=28). Moreover, gene expression profiling suggests that a subset of genes is differentially expressed in aneuploid embryos during the first 30 h of development. Thus, we propose that the chromosomal fate of an embryo is likely determined as early as the pronuclear stage and may be predicted by a 12-gene transcriptomic signature. PMID:26151134

  9. Occurring of In Vitro Functional Vasculogenic Pericytes from Human Circulating Early Endothelial Precursor Cell Culture.

    PubMed

    Cantoni, Silvia; Bianchi, Francesca; Galletti, Margherita; Olivi, Elena; Alviano, Francesco; Galiè, Nazzareno; Ventura, Carlo

    2015-01-01

    Pericytes are periendothelial cells of the microcirculation which contribute to tissue homeostasis and hemostasis by regulating microvascular morphogenesis and stability. Because of their multipotential ex vivo differentiation capabilities, pericytes are becoming very interesting in regenerative medicine field. Several studies address this issue by attempting to isolate pericyte/mesenchymal-like cells from peripheral blood; however the origin of these cells and their culture conditions are still debated. Here we showed that early Endothelial Progenitor Cells (EPCs) expressing CD45+/CD146+/CD31+ can be a source of cells with pericyte/mesenchymal phenotype and function, identified as human Progenitor Perivascular Cells (hPPCs). We provided evidence that hPPCs have an immunophenotype consistent with Mesenchymal Stem Cells (MSCs) from human adipose tissue (hASCs) and fetal membranes of term placenta (FM-hMSCs). In addition, hPPCs can be subcultured and exhibit expression of pluripotent genes (OCT-4, KLF-4, and NANOG) as well as a remarkable vasculogenic potential. Our findings could be helpful to develop innovative cell-based therapies for future clinical applications with distinct therapeutic purposes. PMID:26064139

  10. Structural basis for early-onset neurological disorders caused by mutations in human selenocysteine synthase.

    PubMed

    Puppala, Anupama K; French, Rachel L; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Simonović, Miljan

    2016-01-01

    Selenocysteine synthase (SepSecS) catalyzes the terminal reaction of selenocysteine, and is vital for human selenoproteome integrity. Autosomal recessive inheritance of mutations in SepSecS-Ala239Thr, Thr325Ser, Tyr334Cys and Tyr429*-induced severe, early-onset, neurological disorders in distinct human populations. Although harboring different mutant alleles, patients presented remarkably similar phenotypes typified by cerebellar and cerebral atrophy, seizures, irritability, ataxia, and extreme spasticity. However, it has remained unclear how these genetic alterations affected the structure of SepSecS and subsequently elicited the development of a neurological pathology. Herein, our biophysical and structural characterization demonstrates that, with the exception of Tyr429*, pathogenic mutations decrease protein stability and trigger protein misfolding. We propose that the reduced stability and increased propensity towards misfolding are the main causes for the loss of SepSecS activity in afflicted patients, and that these factors contribute to disease progression. We also suggest that misfolding of enzymes regulating protein synthesis should be considered in the diagnosis and study of childhood neurological disorders. PMID:27576344

  11. Occurring of In Vitro Functional Vasculogenic Pericytes from Human Circulating Early Endothelial Precursor Cell Culture

    PubMed Central

    Bianchi, Francesca; Galletti, Margherita; Galiè, Nazzareno; Ventura, Carlo

    2015-01-01

    Pericytes are periendothelial cells of the microcirculation which contribute to tissue homeostasis and hemostasis by regulating microvascular morphogenesis and stability. Because of their multipotential ex vivo differentiation capabilities, pericytes are becoming very interesting in regenerative medicine field. Several studies address this issue by attempting to isolate pericyte/mesenchymal-like cells from peripheral blood; however the origin of these cells and their culture conditions are still debated. Here we showed that early Endothelial Progenitor Cells (EPCs) expressing CD45+/CD146+/CD31+ can be a source of cells with pericyte/mesenchymal phenotype and function, identified as human Progenitor Perivascular Cells (hPPCs). We provided evidence that hPPCs have an immunophenotype consistent with Mesenchymal Stem Cells (MSCs) from human adipose tissue (hASCs) and fetal membranes of term placenta (FM-hMSCs). In addition, hPPCs can be subcultured and exhibit expression of pluripotent genes (OCT-4, KLF-4, and NANOG) as well as a remarkable vasculogenic potential. Our findings could be helpful to develop innovative cell-based therapies for future clinical applications with distinct therapeutic purposes. PMID:26064139

  12. Increases in Human Papillomavirus Detection During Early HIV Infection Among Women in Zimbabwe

    PubMed Central

    Nowak, Rebecca G.; Morrison, Charles S.; Gange, Stephen J.; Kwok, Cynthia; Oliver, Amy E.; Howard, Roslyn; Van Der Pol, Barbara; Salata, Robert A.; Padian, Nancy S.; Chipato, Tsungai; Munjoma, Marshall; Celentano, David D.

    2011-01-01

    Background. Individuals who acquire human immunodeficiency virus (HIV) may experience an immediate disruption of genital tract immunity, altering the ability to mount a local and effective immune response. This study examined the impact of early HIV infection on new detection of human papillomavirus (HPV). Methods. One hundred fifty-five Zimbabwean women with observation periods before and after HIV acquisition and 486 HIV-uninfected women were selected from a cohort study evaluating hormonal contraceptive use and risk of HIV acquisition. Study visits occurred at 3-month intervals. Cervical swab samples available from up to 6 months before, at, and up to 6 months after the visit when HIV was first detected were typed for 37 HPV genotypes or subtypes. Results. We observed ∼5-fold higher odds of multiple (≥2) new HPV detections only after HIV acquisition, relative to HIV-negative women after adjusting for sexual behavior and concurrent genital tract infections. We also observed ∼2.5-fold higher odds of single new HPV detections at visits before and after HIV acquisition, relative to HIV-uninfected women in multivariable models. Conclusions. These findings suggest that HIV infection has an immediate impact on genital tract immunity, as evidenced by the high risk of multiple new HPV detections immediately after HIV acquisition. PMID:21451006

  13. Confined 3D microenvironment regulates early differentiation in human pluripotent stem cells.

    PubMed

    Giobbe, Giovanni G; Zagallo, Monica; Riello, Massimo; Serena, Elena; Masi, Giulia; Barzon, Luisa; Di Camillo, Barbara; Elvassore, Nicola

    2012-12-01

    The therapeutic potential of human pluripotent stem (hPS) cells is threatened, among various problems, by the difficulty to homogenously direct cell differentiation into specific lineages. The transition from hPSC into committed differentiated cells is accompanied by secretome activity, remodeling of extracellular matrix and self-organization into germ layers. In this work, we aimed to investigate how different three-dimensional microenvironments regulate the early differentiation of the three germ layers in human embryonic stem (hES) cells derived embryoid bodies. In particular, a permeable, biocompatible, hydrogel microwell array was specifically designed for recreating a confined niche in which EB secreted molecules accumulate in accordance with hydrogel diffusional cut-off. Fluorescence recovery after photobleaching technique was performed to accurately evaluate hydrogel permeability, mesh size and diffusional cutoff for soluble molecules. Three different culture conditions of EB culture were analyzed: suspension, confinement in microwells of width/depth ratio 1:1 and 1:2. Results show that EBs cultured in microwells are viable and have comparable average size after 8 days culture. Whole genome microarrays show that significative differential gene expression was observed between suspension and confined EBs culture. In particular, EBs culture in microwells promotes the expression of genes involved in pattern specification processes, brain development, ectoderm and endoderm differentiation. On the contrary, suspension EBs express instead genes involved in mesoderm specification and heart development. These results suggest that local accumulation of EBs secreted molecules drives differentiation patterns, as confirmed by immunofluorescence of germ layer markers, in hydrogel confined EB culture from both hES cells and human induced pluripotent stem (hiPS) cells. Our findings highlight an additional potential role of biomaterial in controlling hPSC differentiation

  14. Development and morphogenesis of human wrist joint during embryonic and early fetal period.

    PubMed

    Hita-Contreras, Fidel; Martínez-Amat, Antonio; Ortiz, Raúl; Caba, Octavio; Alvarez, Pablo; Prados, José C; Lomas-Vega, Rafael; Aránega, Antonia; Sánchez-Montesinos, Indalecio; Mérida-Velasco, Juan A

    2012-06-01

    The development of the human wrist joint has been studied widely, with the main focus on carpal chondrogenesis, ligaments and triangular fibrocartilage. However, there are some discrepancies concerning the origin and morphogenetic time-table of these structures, including nerves, muscles and vascular elements. For this study we used serial sections of 57 human embryonic (n = 30) and fetal (n = 27) specimens from O'Rahilly stages 17-23 and 9-14 weeks, respectively. The following phases in carpal morphogenesis have been established: undifferentiated mesenchyme (stage 17), condensated mesenchyme (stages 18 and 19), pre-chondrogenic (stages 19 and 20) and chondrogenic (stages 21 and over). Carpal chondrification and osteogenic processes are similar, starting with capitate and hamate (stage 19) and ending with pisiform (stage 22). In week 14, a vascular bud penetrates into the lunate cartilaginous mold, early sign of the osteogenic process that will be completed after birth. In stage 18, median, ulnar and radial nerves and thenar eminence appear in the hand plate. In stage 21, there are indications of the interosseous muscles, and in stage 22 flexor digitorum superficialis, flexor digitorum profundus and lumbrical muscles, transverse carpal ligament and collateral ligaments emerge. In stage 23, the articular disc, radiocarpal and ulnocarpal ligaments and deep palmar arterial arch become visible. Radiate carpal and interosseous ligaments appear in week 9, and in week 10, dorsal radiocarpal ligament and articular capsule are evident. Finally, synovial membrane is observed in week 13. We have performed a complete analysis of the morphogenesis of the structures of the human wrist joint. Our results present new data on nervous and arterial elements and provide the basis for further investigations on anatomical pathology, comparative morphology and evolutionary anthropology.

  15. Acute Molecular Changes in Synovial Fluid Following Human Knee Injury: Association With Early Clinical Outcomes

    PubMed Central

    Paterson, Erin; Freidin, Andrew; Kenny, Mark; Judge, Andrew; Saklatvala, Jeremy; Williams, Andy; Vincent, Tonia L.

    2016-01-01

    Objective To investigate whether molecules found to be up‐regulated within hours of surgical joint destabilization in the mouse are also elevated in the analogous human setting of acute knee injury, how this molecular response varies between individuals, and whether it is related to patient‐reported outcomes in the 3 months after injury. Methods Seven candidate molecules were analyzed in blood and synovial fluid (SF) from 150 participants with recent structural knee injury at baseline (<8 weeks from injury) and in blood at 14 days and 3 months following baseline. Knee Injury and Osteoarthritis Outcome Score 4 (KOOS4) was obtained at baseline and 3 months. Patient and control samples were compared using Meso Scale Discovery platform assays or enzyme‐linked immunosorbent assay. Results Six of the 7 molecules were significantly elevated in human SF immediately after injury: interleukin‐6 (IL‐6), monocyte chemotactic protein 1, matrix metalloproteinase 3 (MMP‐3), tissue inhibitor of metalloproteinases 1 (TIMP‐1), activin A, and tumor necrosis factor–stimulated gene 6 (TSG‐6). There was low‐to‐moderate correlation with blood measurements. Three of the 6 molecules were significantly associated with baseline KOOS4 (those with higher SF IL‐6, TIMP‐1, or TSG‐6 had lower KOOS4). These 3 molecules, MMP‐3, and activin A were all significantly associated with greater improvement in KOOS4 over 3 months, after adjustment for other relevant factors. Of these, IL‐6 alone significantly accounted for the molecular contribution to baseline KOOS4 and change in KOOS4 over 3 months. Conclusion Our findings validate relevant human biomarkers of tissue injury identified in a mouse model. Analysis of SF rather than blood more accurately reflects this response. The response is associated with patient‐reported outcomes over this early period, with SF IL‐6 acting as a single representative marker. Longitudinal outcomes will determine if these molecules are

  16. Human evolution.

    PubMed

    Wood, B

    1996-12-01

    The common ancestor of modern humans and the great apes is estimated to have lived between 5 and 8 Myrs ago, but the earliest evidence in the human, or hominid, fossil record is Ardipithecus ramidus, from a 4.5 Myr Ethiopian site. This genus was succeeded by Australopithecus, within which four species are presently recognised. All combine a relatively primitive postcranial skeleton, a dentition with expanded chewing teeth and a small brain. The most primitive species in our own genus, Homo habilis and Homo rudolfensis, are little advanced over the australopithecines and with hindsight their inclusion in Homo may not be appropriate. The first species to share a substantial number of features with later Homo is Homo ergaster, or 'early African Homo erectus', which appears in the fossil record around 2.0 Myr. Outside Africa, fossil hominids appear as Homo erectus-like hominids, in mainland Asia and in Indonesia close to 2 Myr ago; the earliest good evidence of 'archaic Homo' in Europe is dated at between 600-700 Kyr before the present. Anatomically modern human, or Homo sapiens, fossils are seen first in the fossil record in Africa around 150 Kyr ago. Taken together with molecular evidence on the extent of DNA variation, this suggests that the transition from 'archaic' to 'modern' Homo may have taken place in Africa. PMID:8976151

  17. Human evolution.

    PubMed

    Wood, B

    1996-12-01

    The common ancestor of modern humans and the great apes is estimated to have lived between 5 and 8 Myrs ago, but the earliest evidence in the human, or hominid, fossil record is Ardipithecus ramidus, from a 4.5 Myr Ethiopian site. This genus was succeeded by Australopithecus, within which four species are presently recognised. All combine a relatively primitive postcranial skeleton, a dentition with expanded chewing teeth and a small brain. The most primitive species in our own genus, Homo habilis and Homo rudolfensis, are little advanced over the australopithecines and with hindsight their inclusion in Homo may not be appropriate. The first species to share a substantial number of features with later Homo is Homo ergaster, or 'early African Homo erectus', which appears in the fossil record around 2.0 Myr. Outside Africa, fossil hominids appear as Homo erectus-like hominids, in mainland Asia and in Indonesia close to 2 Myr ago; the earliest good evidence of 'archaic Homo' in Europe is dated at between 600-700 Kyr before the present. Anatomically modern human, or Homo sapiens, fossils are seen first in the fossil record in Africa around 150 Kyr ago. Taken together with molecular evidence on the extent of DNA variation, this suggests that the transition from 'archaic' to 'modern' Homo may have taken place in Africa.

  18. Comparing salt tolerance of beet cultivars and their halophytic ancestor: consequences of domestication and breeding programmes.

    PubMed

    Rozema, Jelte; Cornelisse, Danny; Zhang, Yuancheng; Li, Hongxiu; Bruning, Bas; Katschnig, Diana; Broekman, Rob; Ji, Bin; van Bodegom, Peter

    2014-12-09

    Salt tolerance of higher plants is determined by a complex set of traits, the timing and rate of evolution of which are largely unknown. We compared the salt tolerance of cultivars of sugar beet and their ancestor, sea beet, in hydroponic studies and evaluated whether traditional domestication and more recent breeding have changed salt tolerance of the cultivars relative to their ancestor. Our comparison of salt tolerance of crop cultivars is based on values of the relative growth rate (RGR) of the entire plant at various salinity levels. We found considerable salt tolerance of the sea beet and slightly, but significantly, reduced salt tolerance of the sugar beet cultivars. This indicates that traditional domestication by selection for morphological traits such as leaf size, beet shape and size, enhanced productivity, sugar content and palatability slightly affected salt tolerance of sugar beet cultivars. Salt tolerance among four sugar beet cultivars, three of which have been claimed to be salt tolerant, did not differ. We analysed the components of RGR to understand the mechanism of salt tolerance at the whole-plant level. The growth rate reduction at higher salinity was linked with reduced leaf area at the whole-plant level (leaf area ratio) and at the individual leaf level (specific leaf area). The leaf weight fraction was not affected by increased salinity. On the other hand, succulence and leaf thickness and the net assimilation per unit of leaf area (unit leaf rate) increased in response to salt treatment, thus partially counteracting reduced capture of light by lower leaf area. This compensatory mechanism may form part of the salt tolerance mechanism of sea beet and the four studied sugar beet cultivars. Together, our results indicate that domestication of the halophytic ancestor sea beet slightly reduced salt tolerance and that breeding for improved salt tolerance of sugar beet cultivars has not been effective.

  19. Comparing salt tolerance of beet cultivars and their halophytic ancestor: consequences of domestication and breeding programmes

    PubMed Central

    Rozema, Jelte; Cornelisse, Danny; Zhang, Yuancheng; Li, Hongxiu; Bruning, Bas; Katschnig, Diana; Broekman, Rob; Ji, Bin; van Bodegom, Peter

    2015-01-01

    Salt tolerance of higher plants is determined by a complex set of traits, the timing and rate of evolution of which are largely unknown. We compared the salt tolerance of cultivars of sugar beet and their ancestor, sea beet, in hydroponic studies and evaluated whether traditional domestication and more recent breeding have changed salt tolerance of the cultivars relative to their ancestor. Our comparison of salt tolerance of crop cultivars is based on values of the relative growth rate (RGR) of the entire plant at various salinity levels. We found considerable salt tolerance of the sea beet and slightly, but significantly, reduced salt tolerance of the sugar beet cultivars. This indicates that traditional domestication by selection for morphological traits such as leaf size, beet shape and size, enhanced productivity, sugar content and palatability slightly affected salt tolerance of sugar beet cultivars. Salt tolerance among four sugar beet cultivars, three of which have been claimed to be salt tolerant, did not differ. We analysed the components of RGR to understand the mechanism of salt tolerance at the whole-plant level. The growth rate reduction at higher salinity was linked with reduced leaf area at the whole-plant level (leaf area ratio) and at the individual leaf level (specific leaf area). The leaf weight fraction was not affected by increased salinity. On the other hand, succulence and leaf thickness and the net assimilation per unit of leaf area (unit leaf rate) increased in response to salt treatment, thus partially counteracting reduced capture of light by lower leaf area. This compensatory mechanism may form part of the salt tolerance mechanism of sea beet and the four studied sugar beet cultivars. Together, our results indicate that domestication of the halophytic ancestor sea beet slightly reduced salt tolerance and that breeding for improved salt tolerance of sugar beet cultivars has not been effective. PMID:25492122

  20. Ancestor-descendant relationships in evolution: origin of the extant pygmy right whale, Caperea marginata.

    PubMed

    Tsai, Cheng-Hsiu; Fordyce, R Ewan

    2015-01-01

    Ancestor-descendant relationships (ADRs), involving descent with modification, are the fundamental concept in evolution, but are usually difficult to recognize. We examined the cladistic relationship between the only reported fossil pygmy right whale, †Miocaperea pulchra, and its sole living relative, the enigmatic pygmy right whale Caperea marginata, the latter represented by both adult and juvenile specimens. †Miocaperea is phylogenetically bracketed between juvenile and adult Caperea marginata in morphologically based analyses, thus suggesting a possible ADR-the first so far identified within baleen whales (Cetacea: Mysticeti). The †Miocaperea-Caperea lineage may show long-term morphological stasis and, in turn, punctuated equilibrium.

  1. Characterization of the Early Steps of Human Parvovirus B19 Infection

    PubMed Central

    Quattrocchi, Silva; Ruprecht, Nico; Bönsch, Claudia; Bieli, Sven; Zürcher, Christoph; Boller, Klaus; Kempf, Christoph

    2012-01-01

    The early steps of human parvovirus B19 (B19V) infection were investigated in UT7/Epo cells. B19V and its receptor globoside (Gb4Cer) associate with lipid rafts, predominantly of the noncaveolar type. Pharmacological disruption of the lipid rafts inhibited infection when the drug was added prior to virus attachment but not after virus uptake. B19V is internalized by clathrin-dependent endocytosis and spreads rapidly throughout the endocytic pathway, reaching the lysosomal compartment within minutes, where a substantial proportion is degraded. B19V did not permeabilize the endocytic vesicles, indicating a mechanism of endosomal escape without apparent membrane damage. Bafilomycin A1 (BafA1) and NH4Cl, which raise endosomal pH, blocked the infection by preventing endosomal escape, resulting in a massive accumulation of capsids in the lysosomes. In contrast, in the presence of chloroquine (CQ), the transfer of incoming viruses from late endosomes to lysosomes was prevented; the viral DNA was not degraded; and the infection was boosted. In contrast to the findings for untreated or BafA1-treated cells, the viral DNA was progressively associated with the nucleus in CQ-treated cells, reaching a plateau by 3 h postinternalization, a time coinciding with the initiation of viral transcription. At this time, more than half of the total intracellular viral DNA was associated with the nucleus; however, the capsids remained extranuclear. Our studies provide the first insight into the early steps of B19V infection and reveal mechanisms involved in virus uptake, endocytic trafficking, and nuclear penetration. PMID:22718826

  2. Early suppression effect in human primary visual cortex during Kanizsa illusion processing: A magnetoencephalographic evidence.

    PubMed

    Chernyshev, Boris V; Pronko, Platon K; Stroganova, Tatiana A

    2016-01-01

    Detection of illusory contours (ICs) such as Kanizsa figures is known to depend primarily upon the lateral occipital complex. Yet there is no universal agreement on the role of the primary visual cortex in this process; some existing evidence hints that an early stage of the visual response in V1 may involve relative suppression to Kanizsa figures compared with controls. Iso-oriented luminance borders, which are responsible for Kanizsa illusion, may evoke surround suppression in V1 and adjacent areas leading to the reduction in the initial response to Kanizsa figures. We attempted to test the existence, as well as to find localization and timing of the early suppression effect produced by Kanizsa figures in adult nonclinical human participants. We used two sizes of visual stimuli (4.5 and 9.0°) in order to probe the effect at two different levels of eccentricity; the stimuli were presented centrally in passive viewing conditions. We recorded magnetoencephalogram, which is more sensitive than electroencephalogram to activity originating from V1 and V2 areas. We restricted our analysis to the medial occipital area and the occipital pole, and to a 40-120 ms time window after the stimulus onset. By applying threshold-free cluster enhancement technique in combination with permutation statistics, we were able to detect the inverted IC effect-a relative suppression of the response to the Kanizsa figures compared with the control stimuli. The current finding is highly compatible with the explanation involving surround suppression evoked by iso-oriented collinear borders. The effect may be related to the principle of sparse coding, according to which V1 suppresses representations of inner parts of collinear assemblies as being informationally redundant. Such a mechanism is likely to be an important preliminary step preceding object contour detection. PMID:27485162

  3. Osteoarchaeological Studies of Human Systemic Stress of Early Urbanization in Late Shang at Anyang, China.

    PubMed

    Zhang, Hua; Merrett, Deborah C; Jing, Zhichun; Tang, Jigen; He, Yuling; Yue, Hongbin; Yue, Zhanwei; Yang, Dongya Y

    2016-01-01

    Through the analysis of human skeletal remains and mortuary practice in Yinxu, this study investigates the impact of early urbanization on the commoners during the Late Shang dynasty (ca. 1250-1046 B.C.). A total of 347 individuals examined in this study represent non-elites who were recovered from two different burial contexts (formally buried in lineage cemeteries and randomly scattered in refuse pits). Frequencies of enamel hypoplasia (childhood stress), cribra orbitalia (childhood stress and frailty) and osteoperiostitis (adult stress) were examined to assess systemic stress exposure. Our results reveal that there was no significant difference in the frequency of enamel hypoplasia between two burial groups and between sexes, suggesting these urban commoners experienced similar stresses during childhood, but significantly elevated levels of cribra orbitalia and osteoperiostitis were observed in the refuse pit female cohort. Theoretically, urbanization would have resulted in increased population density in the urban centre, declining sanitary conditions, and increased risk of resource shortage. Biologically, children would be more vulnerable to such physiological disturbance; as a result, high percentages of enamel hypoplasia (80.9% overall) and cribra orbitalia (30.3% overall) are observed in Yin commoners. Adults continued to suffer from stress, resulting in high frequencies of osteoperiostitis (40.0% total adults); in particular, in the refuse pit females who may also reflect a compound impact of gender inequality. Our data show that the non-elite urban population in the capital city of Late Shang Dynasty had experienced extensive stress exposure due to early urbanization with further social stratification only worsening the situation, and eventually contributing to collapse of the Shang Dynasty. PMID:27050400

  4. Changing nuclear landscape and unique PML structures during early epigenetic transitions of human embryonic stem cells.

    PubMed

    Butler, John T; Hall, Lisa L; Smith, Kelly P; Lawrence, Jeanne B

    2009-07-01

    The complex nuclear structure of somatic cells is important to epigenomic regulation, yet little is known about nuclear organization of human embryonic stem cells (hESC). Here we surveyed several nuclear structures in pluripotent and transitioning hESC. Observations of centromeres, telomeres, SC35 speckles, Cajal Bodies, lamin A/C and emerin, nuclear shape and size demonstrate a very different "nuclear landscape" in hESC. This landscape is remodeled during a brief transitional window, concomitant with or just prior to differentiation onset. Notably, hESC initially contain abundant signal for spliceosome assembly factor, SC35, but lack discrete SC35 domains; these form as cells begin to specialize, likely reflecting cell-type specific genomic organization. Concomitantly, nuclear size increases and shape changes as lamin A/C and emerin incorporate into the lamina. During this brief window, hESC exhibit dramatically different PML-defined structures, which in somatic cells are linked to gene regulation and cancer. Unlike the numerous, spherical somatic PML bodies, hES cells often display approximately 1-3 large PML structures of two morphological types: long linear "rods" or elaborate "rosettes", which lack substantial SUMO-1, Daxx, and Sp100. These occur primarily between Day 0-2 of differentiation and become rare thereafter. PML rods may be "taut" between other structures, such as centromeres, but clearly show some relationship with the lamina, where PML often abuts or fills a "gap" in early lamin A/C staining. Findings demonstrate that pluripotent hES cells have a markedly different overall nuclear architecture, remodeling of which is linked to early epigenomic programming and involves formation of unique PML-defined structures.

  5. Early and delayed reproductive death in human cells exposed to high energy iron-ion beams

    NASA Astrophysics Data System (ADS)

    Bettega, D.; Calzolari, P.; Doneda, L.; Durante, M.; Tallone, L.

    For radiation protection of the astronauts it is important to know both the acute and the late effects of charged particles. Iron is the most abundant high charge and energy (HZE) specie in galactic cosmic radiation. (HZE) ions are considered to be the major contributors to equivalent dose in space, but the Relative Biological Effectiveness of HZE particles has large uncertainties, expecially for late effects. We have determined early and delayed reproductive death in human fibroblast cells (AG1522) exposed to iron ion beams of energies between 0.2 and 1 GeV/n. The cells were irradiated at the HIMAC accelerator in Chiba (0.2 and 0.5 GeV/n) and at the AGS accelerator at the NASA Space Radiation Laboratory in Brookhaven (1 GeV/n). For each beam the dose--effect curves were measured at least twice in the dose range between 0.5 and 2 Gy. 60 Co gamma rays were used as reference radiation. The following results were obtained: 1) the 1 GeV/n beam effectiveness for inactivation of the AG1522 cells is higher than that of any other beam. 2) the progeny of the irradiated cells show the presence of delayed damage in the form of reproductive death for all the beams with the 1 GeV/n being the most effective. 3) the relative biological effectiveness of the iron beams is higher for delayed compared to early reproductive death. A comparison with preliminary results obtained with 970 MeV/n Ti and 490 MeV/n Si ions will be also reported .

  6. Generation of multipotent early lymphoid progenitors from human embryonic stem cells.

    PubMed

    Larbi, Aniya; Mitjavila-Garcia, Maria Teresa; Flamant, Stéphane; Valogne, Yannick; Clay, Denis; Usunier, Benoît; l'Homme, Bruno; Féraud, Olivier; Casal, Ibrahim; Gobbo, Emilie; Divers, Dominique; Chapel, Alain; Turhan, Ali G; Bennaceur-Griscelli, Annelise; Haddad, Rima

    2014-12-15

    During human embryonic stem cell (ESC) hematopoietic differentiation, the description of the initial steps of lymphopoiesis remains elusive. Using a two-step culture procedure, we identified two original populations of ESC-derived hematopoietic progenitor cells (HPCs) with CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) phenotypes. Bulk cultures and limiting dilution assays, culture with MS5 cells in the presence of Notch ligand Delta-like-1 (DL-1), and ex vivo colonization tests using fetal thymic organ cultures showed that although CD34(+)CD45RA(+)CD7(-) HPCs could generate cells of the three lymphoid lineages, their potential was skewed toward the B cell lineages. In contrast, CD34(+)CD45RA(+)CD7(+) HPCs predominantly exhibited a T/natural killer (NK) cell differentiation potential. Furthermore these cells could differentiate equivalently into cells of the granulo-macrophagic lineage and dendritic cells and lacked erythroid potential. Expression profiling of 18 markers by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed that CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) HPCs express genes of the lymphoid specification and that CD34(+)CD45RA(+)CD7(-) cells express B-cell-associated genes, while CD34(+)CD45RA(+)CD7(+) HPCs display a T-cell molecular profile. Altogether, these findings indicate that CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) HPCs correspond to candidate multipotent early lymphoid progenitors polarized toward either the B or T/NK lineage, respectively. This work should improve our understanding of the early steps of lymphopoiesis from pluripotent stem cells and pave the way for the production of lymphocytes for cell-based immunotherapy and lymphoid development studies.

  7. Vasopressin in preeclampsia: a novel very early human pregnancy biomarker and clinically relevant mouse model.

    PubMed

    Santillan, Mark K; Santillan, Donna A; Scroggins, Sabrina M; Min, James Y; Sandgren, Jeremy A; Pearson, Nicole A; Leslie, Kimberly K; Hunter, Stephen K; Zamba, Gideon K D; Gibson-Corley, Katherine N; Grobe, Justin L

    2014-10-01

    Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, body mass index, chronic essential hypertension, twin gestation, diabetes mellitus, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the sixth week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng per hour) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, identify chronic AVP infusion as a novel and clinically relevant model of preeclampsia in mice, and are consistent with a potential causative role for AVP in preeclampsia in humans.

  8. Osteoarchaeological Studies of Human Systemic Stress of Early Urbanization in Late Shang at Anyang, China.

    PubMed

    Zhang, Hua; Merrett, Deborah C; Jing, Zhichun; Tang, Jigen; He, Yuling; Yue, Hongbin; Yue, Zhanwei; Yang, Dongya Y

    2016-01-01

    Through the analysis of human skeletal remains and mortuary practice in Yinxu, this study investigates the impact of early urbanization on the commoners during the Late Shang dynasty (ca. 1250-1046 B.C.). A total of 347 individuals examined in this study represent non-elites who were recovered from two different burial contexts (formally buried in lineage cemeteries and randomly scattered in refuse pits). Frequencies of enamel hypoplasia (childhood stress), cribra orbitalia (childhood stress and frailty) and osteoperiostitis (adult stress) were examined to assess systemic stress exposure. Our results reveal that there was no significant difference in the frequency of enamel hypoplasia between two burial groups and between sexes, suggesting these urban commoners experienced similar stresses during childhood, but significantly elevated levels of cribra orbitalia and osteoperiostitis were observed in the refuse pit female cohort. Theoretically, urbanization would have resulted in increased population density in the urban centre, declining sanitary conditions, and increased risk of resource shortage. Biologically, children would be more vulnerable to such physiological disturbance; as a result, high percentages of enamel hypoplasia (80.9% overall) and cribra orbitalia (30.3% overall) are observed in Yin commoners. Adults continued to suffer from stress, resulting in high frequencies of osteoperiostitis (40.0% total adults); in particular, in the refuse pit females who may also reflect a compound impact of gender inequality. Our data show that the non-elite urban population in the capital city of Late Shang Dynasty had experienced extensive stress exposure due to early urbanization with further social stratification only worsening the situation, and eventually contributing to collapse of the Shang Dynasty.

  9. Early Intervention for Spinal Cord Injury with Human Induced Pluripotent Stem Cells Oligodendrocyte Progenitors

    PubMed Central

    All, Angelo H.; Gharibani, Payam; Gupta, Siddharth; Bazley, Faith A.; Pashai, Nikta; Chou, Bin-Kuan; Shah, Sandeep; Resar, Linda M.; Cheng, Linzhao; Gearhart, John D.; Kerr, Candace L.

    2015-01-01

    Induced pluripotent stem (iPS) cells are at the forefront of research in regenerative medicine and are envisaged as a source for personalized tissue repair and cell replacement therapy. Here, we demonstrate for the first time that oligodendrocyte progenitors (OPs) can be derived from iPS cells generated using either an episomal, non-integrating plasmid approach or standard integrating retroviruses that survive and differentiate into mature oligodendrocytes after early transplantation into the injured spinal cord. The efficiency of OP differentiation in all 3 lines tested ranged from 40% to 60% of total cells, comparable to those derived from human embryonic stem cells. iPS cell lines derived using episomal vectors or retroviruses generated a similar number of early neural progenitors and glial progenitors while the episomal plasmid-derived iPS line generated more OPs expressing late markers O1 and RIP. Moreover, we discovered that iPS-derived OPs (iPS-OPs) engrafted 24 hours following a moderate contusive spinal cord injury (SCI) in rats survived for approximately two months and that more than 70% of the transplanted cells differentiated into mature oligodendrocytes that expressed myelin associated proteins. Transplanted OPs resulted in a significant increase in the number of myelinated axons in animals that received a transplantation 24 h after injury. In addition, nearly a 5-fold reduction in cavity size and reduced glial scarring was seen in iPS-treated groups compared to the control group, which was injected with heat-killed iPS-OPs. Although further investigation is needed to understand the mechanisms involved, these results provide evidence that patient-specific, iPS-derived OPs can survive for three months and improve behavioral assessment (BBB) after acute transplantation into SCI. This is significant as determining the time in which stem cells are injected after SCI may influence their survival and differentiation capacity. PMID:25635918

  10. Osteoarchaeological Studies of Human Systemic Stress of Early Urbanization in Late Shang at Anyang, China

    PubMed Central

    Zhang, Hua; Merrett, Deborah C.; Jing, Zhichun; Tang, Jigen; He, Yuling; Yue, Hongbin; Yue, Zhanwei; Yang, Dongya Y.

    2016-01-01

    Through the analysis of human skeletal remains and mortuary practice in Yinxu, this study investigates the impact of early urbanization on the commoners during the Late Shang dynasty (ca. 1250–1046 B.C.). A total of 347 individuals examined in this study represent non-elites who were recovered from two different burial contexts (formally buried in lineage cemeteries and randomly scattered in refuse pits). Frequencies of enamel hypoplasia (childhood stress), cribra orbitalia (childhood stress and frailty) and osteoperiostitis (adult stress) were examined to assess systemic stress exposure. Our results reveal that there was no significant difference in the frequency of enamel hypoplasia between two burial groups and between sexes, suggesting these urban commoners experienced similar stresses during childhood, but significantly elevated levels of cribra orbitalia and osteoperiostitis were observed in the refuse pit female cohort. Theoretically, urbanization would have resulted in increased population density in the urban centre, declining sanitary conditions, and increased risk of resource shortage. Biologically, children would be more vulnerable to such physiological disturbance; as a result, high percentages of enamel hypoplasia (80.9% overall) and cribra orbitalia (30.3% overall) are observed in Yin commoners. Adults continued to suffer from stress, resulting in high frequencies of osteoperiostitis (40.0% total adults); in particular, in the refuse pit females who may also reflect a compound impact of gender inequality. Our data show that the non-elite urban population in the capital city of Late Shang Dynasty had experienced extensive stress exposure due to early urbanization with further social stratification only worsening the situation, and eventually contributing to collapse of the Shang Dynasty. PMID:27050400

  11. Ibuprofen treatment blunts early translational signaling responses in human skeletal muscle following resistance exercise.

    PubMed

    Markworth, James F; Vella, Luke D; Figueiredo, Vandre C; Cameron-Smith, David

    2014-07-01

    Cyclooxygenase-1 and -2 pathway-derived prostaglandins (PGs) have been implicated in adaptive muscle responses to exercise, but the role of PGs in contraction-induced muscle signaling has not been determined. We investigated the effect of inhibition of cyclooxygenase-1 and -2 activities with the nonsteroidal anti-inflammatory drug ibuprofen on human muscle signaling responses to resistance exercise. Subjects orally ingested 1,200 mg ibuprofen (or placebo control) in three 400-mg doses administered ∼30 min before and ∼6 h and ∼12 h following a bout of unaccustomed resistance exercise (80% one repetition maximum). Muscle biopsies were obtained at rest (preexercise), immediately postexercise (0 h), 3 h postexercise, and at 24 h of recovery. In the placebo (PLA) group, phosphorylation of ERK1/2 (Thr202/Tyr204), ribosomal protein S6 kinase (RSK, Ser380), mitogen-activated kinase 1 (Mnk1, Thr197/202), and p70S6 kinase (p70S6K, Thr421/Ser424) increased at both 0 and 3 h postexercise, with delayed elevation of phospho (p)-p70S6K (Thr389) and p-rpS6 (Ser235/S36 and Ser240/244) at 3 h postexercise. Only p-ERK1/2 (Thr202/Tyr204) remained significantly elevated in the 24-h postexercise biopsy. Ibuprofen treatment prevented sustained elevation of MEK-ERK signaling at 3 h (p-ERK1/2, p-RSK, p-Mnk1, p-p70S6K Thr421/Ser424) and 24 h (p-ERK1/2) postexercise, and this was associated with suppressed phosphorylation of ribosomal protein S6 (Ser235/236 and Ser240/244). Early contraction-induced p-Akt (Ser473) and p-p70S6K (Thr389) were not influenced by ibuprofen, but p-p70S6K (Thr389) remained elevated 24 h postexercise only in those receiving ibuprofen treatment. Early muscle signaling responses to resistance exercise are, in part, ibuprofen sensitive, suggesting that PGs are important signaling molecules during early postexercise recovery.

  12. Metabolomic markers reveal novel pathways of ageing and early development in human populations

    PubMed Central

    Menni, Cristina; Kastenmüller, Gabriella; Petersen, Ann Kristin; Bell, Jordana T; Psatha, Maria; Tsai, Pei-Chien; Gieger, Christian; Schulz, Holger; Erte, Idil; John, Sally; Brosnan, M Julia; Wilson, Scott G; Tsaprouni, Loukia; Lim, Ee Mun; Stuckey, Bronwyn; Deloukas, Panos; Mohney, Robert; Suhre, Karsten; Spector, Tim D; Valdes, Ana M

    2013-01-01

    Background Human ageing is a complex, multifactorial process and early developmental factors affect health outcomes in old age. Methods Metabolomic profiling on fasting blood was carried out in 6055 individuals from the UK. Stepwise regression was performed to identify a panel of independent metabolites which could be used as a surrogate for age. We also investigated the association with birthweight overall and within identical discordant twins and with genome-wide methylation levels. Results We identified a panel of 22 metabolites which combined are strongly correlated with age (R2 = 59%) and with age-related clinical traits independently of age. One particular metabolite, C-glycosyl tryptophan (C-glyTrp), correlated strongly with age (beta = 0.03, SE = 0.001, P = 7.0 × 10−157) and lung function (FEV1 beta = −0.04, SE = 0.008, P = 1.8 × 10−8 adjusted for age and confounders) and was replicated in an independent population (n = 887). C-glyTrp was also associated with bone mineral density (beta = −0.01, SE = 0.002, P = 1.9 × 10−6) and birthweight (beta = −0.06, SE = 0.01, P = 2.5 × 10−9). The difference in C-glyTrp levels explained 9.4% of the variance in the difference in birthweight between monozygotic twins. An epigenome-wide association study in 172 individuals identified three CpG-sites, associated with levels of C-glyTrp (P < 2 × 10−6). We replicated one CpG site in the promoter of the WDR85 gene in an independent sample of 350 individuals (beta = −0.20, SE = 0.04, P = 2.9 × 10−8). WDR85 is a regulator of translation elongation factor 2, essential for protein synthesis in eukaryotes. Conclusions Our data illustrate how metabolomic profiling linked with epigenetic studies can identify some key molecular mechanisms potentially determined in early development that produce long-term physiological changes influencing human health and ageing. PMID:23838602

  13. Role of human cytomegalovirus in the proliferation and invasion of extravillous cytotrophoblasts isolated from early placentae

    PubMed Central

    Liu, Tao; Zheng, Xiaofei; Li, Qin; Chen, Juanjuan; Yin, Zongzhi; Xiao, Juan; Zhang, Dandan; Li, Wei; Qiao, Yuan; Chen, Suhua

    2015-01-01

    Aim: We investigated the role of human cytomegalovirus (HCMV) and its mechanism in extravillous cytotrophoblast (EVT) proliferation and invasion in vitro. Methods: Differential enzymatic digestion combined with gradient centrifugation, was used to isolate primary EVT from human chorionic villi collected from early placentae of healthy pregnant women. HCMV infection was determined by immunofluorescence staining of HCMVpp65 antigen expression. An MTT assay was used to examine the role of HCMV in the proliferation of EVT. Quantitative real-time polymerase chain reaction (qRT-PCR), immunocytochemical staining and Western blots were carried out in a control group (EVT) and a virus group (EVT+HCMV) to examine the expression of major genes and protein in TGF-β/Smad signaling pathways in EVT 48 h after inoculation with HCMV. An in vitro cell invasion assay was performed to analyze the influence of HCMV on EVT invasion. Results: HCMV significantly inhibited the proliferation of EVT 48 h after viral infection (P < 0.05). The expression of TGF-β1, Smad1, Smad2, Smad3, Smad4, and Smad5 genes was significantly increased (P < 0.05), but that of TGF-β2, TGF-β3, TGFβRI, TGFβRII, Smad7, MMP2, and MMP9 was significantly decreased in the virus group 48 h after HCMV infection (P < 0.05). Smad7, MMP-2 and MMP-9 protein levels were significantly decreased and the TGF-β1 protein level was significantly increased in infected EVT (all P < 0.05). Conclusions: HCMV may act on multiple steps of the TGF-β/Smad signaling pathway to impede EVT proliferation and invasion. PMID:26770317

  14. Chimerism in humans after intragenic recombination at the haptoglobin locus during early embryogenesis.

    PubMed

    Asakawa, J; Kodaira, M; Nakamura, N; Satoh, C; Fujita, M

    1999-08-31

    The human haptoglobin (HP) HP*2 allele contains a 1.7-kilobase (kb) intragenic duplication that arose after a unique nonhomologous recombination between the prototype HP*1 alleles. During a genetic screening of 13,000 children of survivors exposed to atomic-bomb radiation and 10,000 children of unexposed persons, two children suspected of carrying de novo mutations at the haptoglobin locus were identified (one in each group). DNA analyses of single-cell-derived colonies of Epstein-Barr virus-transformed B cells revealed that the two children were mosaics comprising HP*2/HP*2 and HP*2/HP*1 cells at a ratio of approximately 3:1. We infer that the latter cells are caused by reversion of one HP*2 allele to HP*1 through an intramolecular homologous recombination between the duplicated segments of the Hp*2 allele that excised one of the segments. Because the mosaicism is substantial (approximately 25%), this recombination must have occurred in early embryogenesis. The frequency of finding these children and the extent of their mosaicisms corresponds to an HP*2 to HP*1 reversion rate of 8 x 10(-6) per cell during development. This leads to the prediction that the HP*1 allele also will be represented, although usually at a very low frequency, in any HP2-2 person. We tested this prediction by using PCR for a single individual and found the HP*1 allele at frequencies of 4 x 10(-6) and 3 x 10(-6) in somatic and sperm cells. The HP*1 allele was detected by PCR in all four other HP2-2 individuals, which supports the regular but rare occurrence somatically of homologous recombination within duplicated regions in humans, in agreement with previous observations in mouse and Drosophila. PMID:10468605

  15. A Study of Early Afterdepolarizations in a Model for Human Ventricular Tissue

    PubMed Central

    Vandersickel, Nele; Kazbanov, Ivan V.; Nuitermans, Anita; Weise, Louis D.; Pandit, Rahul; Panfilov, Alexander V.

    2014-01-01

    Sudden cardiac death is often caused by cardiac arrhythmias. Recently, special attention has been given to a certain arrhythmogenic condition, the long-QT syndrome, which occurs as a result of genetic mutations or drug toxicity. The underlying mechanisms of arrhythmias, caused by the long-QT syndrome, are not fully understood. However, arrhythmias are often connected to special excitations of cardiac cells, called early afterdepolarizations (EADs), which are depolarizations during the repolarizing phase of the action potential. So far, EADs have been studied mainly in isolated cardiac cells. However, the question on how EADs at the single-cell level can result in fibrillation at the tissue level, especially in human cell models, has not been widely studied yet. In this paper, we study wave patterns that result from single-cell EAD dynamics in a mathematical model for human ventricular cardiac tissue. We induce EADs by modeling experimental conditions which have been shown to evoke EADs at a single-cell level: by an increase of L-type Ca currents and a decrease of the delayed rectifier potassium currents. We show that, at the tissue level and depending on these parameters, three types of abnormal wave patterns emerge. We classify them into two types of spiral fibrillation and one type of oscillatory dynamics. Moreover, we find that the emergent wave patterns can be driven by calcium or sodium currents and we find phase waves in the oscillatory excitation regime. From our simulations we predict that arrhythmias caused by EADs can occur during normal wave propagation and do not require tissue heterogeneities. Experimental verification of our results is possible for experiments at the cell-culture level, where EADs can be induced by an increase of the L-type calcium conductance and by the application of I blockers, and the properties of the emergent patterns can be studied by optical mapping of the voltage and calcium. PMID:24427289

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

    PubMed

    Will, Manuel; Mackay, Alex; Phillips, Natasha

    2015-01-01

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

  17. EFFECT OF ARSENICALS ON THE EXPRESSION OF CELL CYCLE PROTEINS AND EARLY SIGNALING EVENTS IN PRIMARY HUMAN KERATINOCYTES.

    EPA Science Inventory

    Effect of Arsenicals on the Expression of Cell Cycle Proteins and Early Signaling Events in Primary Human Keratinocytes.

    Mudipalli, A, Owen R. D. and R. J. Preston, Environmental Carcinogenesis Division, USEPA, RTP, NC 27711.

    Environmental exposure to arsenic is a m...

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

    PubMed Central

    Phillips, Natasha

    2015-01-01

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

  19. Did Viruses Evolve As a Distinct Supergroup from Common Ancestors of Cells?

    PubMed Central

    Harish, Ajith; Abroi, Aare; Gough, Julian; Kurland, Charles

    2016-01-01

    The evolutionary origins of viruses according to marker gene phylogenies, as well as their relationships to the ancestors of host cells remains unclear. In a recent article Nasir and Caetano-Anollés reported that their genome-scale phylogenetic analyses based on genomic composition of protein structural-domains identify an ancient origin of the “viral supergroup” (Nasir et al. 2015. A phylogenomic data-driven exploration of viral origins and evolution. Sci Adv. 1(8):e1500527.). It suggests that viruses and host cells evolved independently from a universal common ancestor. Examination of their data and phylogenetic methods indicates that systematic errors likely affected the results. Reanalysis of the data with additional tests shows that small-genome attraction artifacts distort their phylogenomic analyses, particularly the location of the root of the phylogenetic tree of life that is central to their conclusions. These new results indicate that their suggestion of a distinct ancestry of the viral supergroup is not well supported by the evidence. PMID:27497315

  20. Pseudogenization of the tooth gene enamelysin (MMP20) in the common ancestor of extant baleen whales.

    PubMed

    Meredith, Robert W; Gatesy, John; Cheng, Joyce; Springer, Mark S

    2011-04-01

    Whales in the suborder Mysticeti are filter feeders that use baleen to sift zooplankton and small fish from ocean waters. Adult mysticetes lack teeth, although tooth buds are present in foetal stages. Cladistic analyses suggest that functional teeth were lost in the common ancestor of crown-group Mysticeti. DNA sequences for the tooth-specific genes, ameloblastin (AMBN), enamelin (ENAM) and amelogenin (AMEL), have frameshift mutations and/or stop codons in this taxon, but none of these molecular cavities are shared by all extant mysticetes. Here, we provide the first evidence for pseudogenization of a tooth gene, enamelysin (MMP20), in the common ancestor of living baleen whales. Specifically, pseudogenization resulted from the insertion of a CHR-2 SINE retroposon in exon 2 of MMP20. Genomic and palaeontological data now provide congruent support for the loss of enamel-capped teeth on the common ancestral branch of crown-group mysticetes. The new data for MMP20 also document a polymorphic stop codon in exon 2 of the pygmy sperm whale (Kogia breviceps), which has enamel-less teeth. These results, in conjunction with the evidence for pseudogenization of MMP20 in Hoffmann's two-toed sloth (Choloepus hoffmanni), another enamel-less species, support the hypothesis that the only unique, non-overlapping function of the MMP20 gene is in enamel formation.

  1. Evidence of duplicated Hox genes in the most recent common ancestor of extant scorpions.

    PubMed

    Sharma, Prashant P; Santiago, Marc A; González-Santillán, Edmundo; Monod, Lionel; Wheeler, Ward C

    2015-01-01

    Scorpions (order Scorpiones) are unusual among arthropods, both for the extreme heteronomy of their bauplan and for the high gene family turnover exhibited in their genomes. These phenomena appear to be correlated, as two scorpion species have been shown to possess nearly twice the number of Hox genes present in most arthropods. Segmentally offset anterior expression boundaries of a subset of Hox paralogs have been shown to correspond to transitions in segmental identities in the scorpion posterior tagmata, suggesting that posterior heteronomy in scorpions may have been achieved by neofunctionalization of Hox paralogs. However, both the first scorpion genome sequenced and the developmental genetic data are based on exemplars of Buthidae, one of 19 families of scorpions. It is therefore not known whether Hox paralogy is limited to Buthidae or widespread among scorpions. We surveyed 24 high throughput transcriptomes and the single whole genome available for scorpions, in order to test the prediction that Hox gene duplications are common to the order. We used gene tree parsimony to infer whether the paralogy was consistent with a duplication event in the scorpion common ancestor. Here we show that duplicated Hox genes in non-buthid scorpions occur in six of the ten Hox classes. Gene tree topologies and parsimony-based reconciliation of the gene trees are consistent with a duplication event in the most recent common ancestor of scorpions. These results suggest that a Hox paralogy, and by extension the model of posterior patterning established in a buthid, can be extended to non-Buthidae scorpions.

  2. Did Viruses Evolve As a Distinct Supergroup from Common Ancestors of Cells?

    PubMed

    Harish, Ajith; Abroi, Aare; Gough, Julian; Kurland, Charles

    2016-01-01

    The evolutionary origins of viruses according to marker gene phylogenies, as well as their relationships to the ancestors of host cells remains unclear. In a recent article Nasir and Caetano-Anollés reported that their genome-scale phylogenetic analyses based on genomic composition of protein structural-domains identify an ancient origin of the "viral supergroup" (Nasir et al. 2015. A phylogenomic data-driven exploration of viral origins and evolution. Sci Adv. 1(8):e1500527.). It suggests that viruses and host cells evolved independently from a universal common ancestor. Examination of their data and phylogenetic methods indicates that systematic errors likely affected the results. Reanalysis of the data with additional tests shows that small-genome attraction artifacts distort their phylogenomic analyses, particularly the location of the root of the phylogenetic tree of life that is central to their conclusions. These new results indicate that their suggestion of a distinct ancestry of the viral supergroup is not well supported by the evidence.

  3. Pseudogenization of the tooth gene enamelysin (MMP20) in the common ancestor of extant baleen whales

    PubMed Central

    Meredith, Robert W.; Gatesy, John; Cheng, Joyce; Springer, Mark S.

    2011-01-01

    Whales in the suborder Mysticeti are filter feeders that use baleen to sift zooplankton and small fish from ocean waters. Adult mysticetes lack teeth, although tooth buds are present in foetal stages. Cladistic analyses suggest that functional teeth were lost in the common ancestor of crown-group Mysticeti. DNA sequences for the tooth-specific genes, ameloblastin (AMBN), enamelin (ENAM) and amelogenin (AMEL), have frameshift mutations and/or stop codons in this taxon, but none of these molecular cavities are shared by all extant mysticetes. Here, we provide the first evidence for pseudogenization of a tooth gene, enamelysin (MMP20), in the common ancestor of living baleen whales. Specifically, pseudogenization resulted from the insertion of a CHR-2 SINE retroposon in exon 2 of MMP20. Genomic and palaeontological data now provide congruent support for the loss of enamel-capped teeth on the common ancestral branch of crown-group mysticetes. The new data for MMP20 also document a polymorphic stop codon in exon 2 of the pygmy sperm whale (Kogia breviceps), which has enamel-less teeth. These results, in conjunction with the evidence for pseudogenization of MMP20 in Hoffmann's two-toed sloth (Choloepus hoffmanni), another enamel-less species, support the hypothesis that the only unique, non-overlapping function of the MMP20 gene is in enamel formation. PMID:20861053

  4. Metabolic effects of growth factors and polycyclic aromatic hydrocarbons on cultured human placental cells of early and late gestation

    SciTech Connect

    Guyda, H.J. )

    1991-03-01

    The metabolic effects of epidermal growth factor (EGF), insulin, insulin-like growth factor-I (IGF-I), and IGF-II were determined on human placental cells in monolayer culture obtained from early gestation (less than 20 weeks) and late gestation (38-42 weeks). Parameters studied were uptake of aminoisobutyric acid (AIB), uptake of 3-O-methylglucose and (3H)thymidine incorporation into cell protein. Since benzo(alpha)pyrene (BP) inhibits EGF binding and autophosphorylation in cultured human placental cells, particularly in early gestation, we also studied the effect of benzo(alpha)pyrene and other polycyclic aromatic hydrocarbons (PAHs) on EGF-mediated AIB uptake. The metabolic effects of EGF, insulin, and the IGFs in cultured human placental cells varied with gestational age and the growth factor studied. All three classes of growth factors stimulated AIB uptake in both early and late gestation at concentrations from 10-100 micrograms/L, well within a physiological range. However, insulin stimulation of AIB uptake was maximal at a high concentration in both early and late gestation cells, suggesting an action via type 1 IGF receptors rather than via insulin receptors. EGF stimulated 3-O-methylglucose uptake only in term placental cells. No significant stimulation of (3H)thymidine incorporation by any of the growth factors tested was seen with either early or late gestation cells. The effect of PAHs on AIB uptake by cultured placental cells was variable. BP alone stimulated AIB uptake by both very early and late gestation cells and enhanced EGF-stimulated AIB uptake. alpha-naphthoflavone alone inhibited AIB uptake at all gestational ages and inhibited EGF-stimulated AIB uptake. beta-Naphthoflavone and 3-methylcholanthrene minimally inhibited AIB uptake by early gestation cells and did not modify EGF-stimulated uptake at any gestational period.

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2015-10-01

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

  7. The Human Factors of an Early Space Accident: Flight 3-65 of the X-15

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Statler, Irving C.; Orr, Jeb S.

    2015-01-01

    The X-15 was a critical research vehicle in the early days of space flight. On November 15, 1967, the X-15-3 suffered an in-flight breakup. This 191st flight of the X-15 and the 65th flight of this third configuration was the only fatal accident of the X-15 program. This paper presents an analysis, from a human factors perspective, of the events that led up to the accident. The analysis is based on the information contained in the report of the Air Force-NASA Accident Investigation Board (AIB) dated January, 1968. The AIBs analysis addressed, primarily, the events that occurred subsequent to the pilots taking direct control of the reaction control system. The analysis described here suggests that all of the events that caused the accident occurred well before the moment when the pilot switched to direct control. Consequently, the analyses and conclusions regarding the causal factors of, and the contributing factors to, the loss of Flight 3-65 presented here differ from those of the AIB based on the same evidence. Although the accident occurred in 1967, the results of the presented analysis are still relevant today. We present our analysis and discuss its implications for the safety of space operations.

  8. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin.

    PubMed Central

    Barber, A J; Lieth, E; Khin, S A; Antonetti, D A; Buchanan, A G; Gardner, T W

    1998-01-01

    This study determined whether retinal degeneration during diabetes includes retinal neural cell apoptosis. Image analysis of retinal sections from streptozotocin (STZ) diabetic rats after 7.5 months of STZ diabetes identified 22% and 14% reductions in the thickness of the inner plexiform and inner nuclear layers, respectively (P < 0. 001). The number of surviving ganglion cells was also reduced by 10% compared to controls (P < 0.001). In situ end labeling of DNA terminal dUTP nick end labeling (TUNEL) identified a 10-fold increase in the frequency of retinal apoptosis in whole-mounted rat retinas after 1, 3, 6, and 12 months of diabetes (P < 0.001, P < 0. 001, P < 0.01, and P < 0.01, respectively). Most TUNEL-positive cells were not associated with blood vessels and did not colocalize with the endothelial cell-specific antigen, von Willebrand factor. Insulin implants significantly reduced the number of TUNEL-positive cells (P < 0.05). The number of TUNEL-positive cells was also increased in retinas from humans with diabetes. These data indicate that retinal neural cell death occurs early in diabetes. This is the first quantitative report of an increase in neural cell apoptosis in the retina during diabetes, and indicates that neurodegeneration is an important component of diabetic retinopathy. PMID:9710447

  9. Gene pathway development in human epicardial adipose tissue during early life

    PubMed Central

    Ojha, Shalini; Fainberg, Hernan P.; Wilson, Victoria; Pelella, Giuseppe; Castellanos, Marcos; May, Sean T.; Lotto, Attilio A.; Sacks, Harold; Symonds, Michael E.; Budge, Helen

    2016-01-01

    Studies in rodents and newborn humans demonstrate the influence of brown adipose tissue (BAT) in temperature control and energy balance and a critical role in the regulation of body weight. Here, we obtained samples of epicardial adipose tissue (EAT) from neonates, infants, and children in order to evaluate changes in their transcriptional landscape by applying a systems biology approach. Surprisingly, these analyses revealed that the transition to infancy is a critical stage for changes in the morphology of EAT and is reflected in unique gene expression patterns of a substantial proportion of thermogenic gene transcripts (~10%). Our results also indicated that the pattern of gene expression represents a distinct developmental stage, even after the rebound in abundance of thermogenic genes in later childhood. Using weighted gene coexpression network analyses, we found precise anthropometric-specific correlations with changes in gene expression and the decline of thermogenic capacity within EAT. In addition, these results indicate a sequential order of transcriptional events affecting cellular pathways, which could potentially explain the variation in the amount, or activity, of BAT in adulthood. Together, these results provide a resource to elucidate gene regulatory mechanisms underlying the progressive development of BAT during early life.

  10. In-vivo measurement of intrauterine gases and acid-base values early in human pregnancy.

    PubMed

    Jauniaux, E; Watson, A; Ozturk, O; Quick, D; Burton, G

    1999-11-01

    A new multiparameter sensor that combines electrochemical and fibre-optic technology was used for continuous in-vivo investigation of pH, carbon dioxide partial pressure (PCO(2)), oxygen partial pressure (PO(2)), bicarbonate concentration (HCO(3)(-)), base excess, and oxygen saturation (O(2)Sat) early in human pregnancy. The sensor was inserted into the amniotic cavity and the placental bed of 16 pregnancies at 10-15 weeks gestation, before termination under general anaesthesia. Amniotic fluid and retroplacental blood from the same site were also aspirated and analysed by means of cartridges and a portable blood gas analyser. Eleven series of measurements were obtained. The variation in measurements over the 5 min of monitoring was

  11. The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus

    PubMed Central

    Cohen, Tobias; Schwarz, Toni M.; Vigant, Frederic; Gardner, Thomas J.; Hernandez, Rosmel E.; Lee, Benhur; Tortorella, Domenico

    2016-01-01

    Human cytomegalovirus is a ubiquitous β-herpesvirus that infects many different cell types through an initial binding to cell surface receptors followed by a fusion event at the cell membrane or endocytic vesicle. A recent high-throughput screen to identify compounds that block a step prior to viral gene expression identified podofilox as a potent and nontoxic inhibitor. Time-of-addition studies in combination with quantitative-PCR analysis demonstrated that podofilox limits an early step of virus entry at the cell surface. Podofilox was also able to drastically reduce infection by herpes simplex 1, an α-herpesvirus with a very similar entry process to CMV. Podofilox caused a reduced maximal plateau inhibition of infection by viruses with single step binding processes prior to fusion-like Newcastle disease virus, Sendai virus, and influenza A virus or viruses that enter via endocytosis like vesicular stomatitis virus and a clinical-like strain of CMV. These results indicate that microtubules appear to be participating in the post-binding step of virus entry including the pre- and post-penetration events. Modulation of the plasma membrane is required to promote virus entry for herpesviruses, and that podofilox, unlike colchicine or nocodazole, is able to preferentially target microtubule networks at the plasma membrane. PMID:27783035

  12. Monitoring chicken flock behaviour provides early warning of infection by human pathogen Campylobacter

    PubMed Central

    Colles, Frances M.; Cain, Russell J.; Nickson, Thomas; Smith, Adrian L.; Roberts, Stephen J.; Maiden, Martin C. J.; Lunn, Daniel; Dawkins, Marian Stamp

    2016-01-01

    Campylobacter is the commonest bacterial cause of gastrointestinal infection in humans, and chicken meat is the major source of infection throughout the world. Strict and expensive on-farm biosecurity measures have been largely unsuccessful in controlling infection and are hampered by the time needed to analyse faecal samples, with the result that Campylobacter status is often known only after a flock has been processed. Our data demonstrate an alternative approach that monitors the behaviour of live chickens with cameras and analyses the ‘optical flow’ patterns made by flock movements. Campylobacter-free chicken flocks have higher mean and lower kurtosis of optical flow than those testing positive for Campylobacter by microbiological methods. We show that by monitoring behaviour in this way, flocks likely to become positive can be identified within the first 7–10 days of life, much earlier than conventional on-farm microbiological methods. This early warning has the potential to lead to a more targeted approach to Campylobacter control and also provides new insights into possible sources of infection that could transform the control of this globally important food-borne pathogen. PMID:26740618

  13. Monitoring chicken flock behaviour provides early warning of infection by human pathogen Campylobacter.

    PubMed

    Colles, Frances M; Cain, Russell J; Nickson, Thomas; Smith, Adrian L; Roberts, Stephen J; Maiden, Martin C J; Lunn, Daniel; Dawkins, Marian Stamp

    2016-01-13

    Campylobacter is the commonest bacterial cause of gastrointestinal infection in humans, and chicken meat is the major source of infection throughout the world. Strict and expensive on-farm biosecurity measures have been largely unsuccessful in controlling infection and are hampered by the time needed to analyse faecal samples, with the result that Campylobacter status is often known only after a flock has been processed. Our data demonstrate an alternative approach that monitors the behaviour of live chickens with cameras and analyses the 'optical flow' patterns made by flock movements. Campylobacter-free chicken flocks have higher mean and lower kurtosis of optical flow than those testing positive for Campylobacter by microbiological methods. We show that by monitoring behaviour in this way, flocks likely to become positive can be identified within the first 7-10 days of life, much earlier than conventional on-farm microbiological methods. This early warning has the potential to lead to a more targeted approach to Campylobacter control and also provides new insights into possible sources of infection that could transform the control of this globally important food-borne pathogen.

  14. Monitoring chicken flock behaviour provides early warning of infection by human pathogen Campylobacter.

    PubMed

    Colles, Frances M; Cain, Russell J; Nickson, Thomas; Smith, Adrian L; Roberts, Stephen J; Maiden, Martin C J; Lunn, Daniel; Dawkins, Marian Stamp

    2016-01-13

    Campylobacter is the commonest bacterial cause of gastrointestinal infection in humans, and chicken meat is the major source of infection throughout the world. Strict and expensive on-farm biosecurity measures have been largely unsuccessful in controlling infection and are hampered by the time needed to analyse faecal samples, with the result that Campylobacter status is often known only after a flock has been processed. Our data demonstrate an alternative approach that monitors the behaviour of live chickens with cameras and analyses the 'optical flow' patterns made by flock movements. Campylobacter-free chicken flocks have higher mean and lower kurtosis of optical flow than those testing positive for Campylobacter by microbiological methods. We show that by monitoring behaviour in this way, flocks likely to become positive can be identified within the first 7-10 days of life, much earlier than conventional on-farm microbiological methods. This early warning has the potential to lead to a more targeted approach to Campylobacter control and also provides new insights into possible sources of infection that could transform the control of this globally important food-borne pathogen. PMID:26740618

  15. The Human Factors of an Early Space Accident: Flight 3-65 of the X-15

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Statler, Irving C.; Orr, Jeb S.

    2016-01-01

    The X-15 was a critical research vehicle in the early days of space flight. On November 15, 1967, the X-15-3 suffered an in-flight breakup. This 191st flight of the X-15 and the 65th flight of this third configuration was the only fatal accident of the X-15 program. This paper presents an analysis, from a human factors perspective, of the events that led up to the accident. The analysis is based on the information contained in the report of the Air Force-NASA Accident Investigation Board (AIB) dated January, 1968. The AIBs analysis addressed, primarily, the events that occurred subsequent to the pilot's taking direct control of the reaction control system. The analysis described here suggests that, rather than events following the pilot's switch to direct control, it was the events preceding the switch that led to the accident. Consequently, the analyses and conclusions regarding the causal factors of, and the contributing factors to, the loss of Flight 3-65 presented here differ from those of the AIB based on the same evidence. Although the accident occurred in 1967, the results of the presented analysis are still relevant today. We present our analysis and discuss its implications for the safety of space operations.

  16. Gene pathway development in human epicardial adipose tissue during early life

    PubMed Central

    Ojha, Shalini; Fainberg, Hernan P.; Wilson, Victoria; Pelella, Giuseppe; Castellanos, Marcos; May, Sean T.; Lotto, Attilio A.; Sacks, Harold; Symonds, Michael E.; Budge, Helen

    2016-01-01

    Studies in rodents and newborn humans demonstrate the influence of brown adipose tissue (BAT) in temperature control and energy balance and a critical role in the regulation of body weight. Here, we obtained samples of epicardial adipose tissue (EAT) from neonates, infants, and children in order to evaluate changes in their transcriptional landscape by applying a systems biology approach. Surprisingly, these analyses revealed that the transition to infancy is a critical stage for changes in the morphology of EAT and is reflected in unique gene expression patterns of a substantial proportion of thermogenic gene transcripts (~10%). Our results also indicated that the pattern of gene expression represents a distinct developmental stage, even after the rebound in abundance of thermogenic genes in later childhood. Using weighted gene coexpression network analyses, we found precise anthropometric-specific correlations with changes in gene expression and the decline of thermogenic capacity within EAT. In addition, these results indicate a sequential order of transcriptional events affecting cellular pathways, which could potentially explain the variation in the amount, or activity, of BAT in adulthood. Together, these results provide a resource to elucidate gene regulatory mechanisms underlying the progressive development of BAT during early life. PMID:27699231

  17. Ordinary Variations in Human Maternal Caregiving in Infancy and Biobehavioral Development in Early Childhood: A Follow-up Study

    PubMed Central

    Hane, Amie Ashley; Henderson, Heather A.; Fox, Nathan A.; Reeb-Sutherland, Bethany C.

    2016-01-01

    Rodent models of early caregiving find that pups reared by dams providing low levels of early stimulation subsequently display heightened stress reactivity and social aggression. We examined these effects in humans by investigating the effects of early caregiving on markers of biobehavioral development at ages 2 and 3 years. This study extended the findings reported by Hane and Fox (2006) in which 185 mothers and infants were observed and scored for variations in maternal caregiving behavior (MCB) at age 9 months. Relative to young children who received high quality MCB in infancy, those who received low-quality MCB showed significantly higher socially inhibited behavior with adults, right frontal electroencephalographam (EEG) asymmetry, aggressive play, and maternal reported internalizing behavior problems and anger proneness. These effects were independent of early temperamental reactivity. Results parallel rodent models and demonstrate that ordinary variations in MCB influence stress reactivity and social behavior in young children. (149 words) PMID:20806328

  18. Early Transcriptomic Response to LDL and oxLDL in Human Vascular Smooth Muscle Cells

    PubMed Central

    Damián-Zamacona, Salvador; Toledo-Ibelles, Paola; Ibarra-Abundis, Mabel Z.; Uribe-Figueroa, Laura; Hernández-Lemus, Enrique; Macedo-Alcibia, Karla Paola; Delgado–Coello, Blanca; Mas-Oliva, Jaime; Reyes-Grajeda, Juan Pablo

    2016-01-01

    Background Although nowadays it is well known that the human transcriptome can importantly vary according to external or environmental condition, the reflection of this concept when studying oxidative stress and its direct relationship with gene expression profiling during the process of atherogenesis has not been thoroughly achieved. Objective The ability to analyze genome-wide gene expression through transcriptomics has shown that the genome responds dynamically to diverse stimuli. Here, we describe the transcriptome of human vascular smooth muscle cells (hVSMC) stimulated by native and oxidized low-density lipoprotein (nLDL and oxLDL respectively), with the aim of assessing the early molecular changes that induce a response in this cell type resulting in a transcriptomic transformation. This expression has been demonstrated in atherosclerotic plaques in vivo and in vitro, particularly in the light of the oxidative modification hypothesis of atherosclerosis. Approach and Results Total RNA was isolated with TRIzol reagent (Life Technologies) and quality estimated using an Agilent 2100 bioanalyzer. The transcriptome of hVSMC under different experimental conditions (1,5 and 24 hours for nLDL and oxLDL) was obtained using the GeneChip Human Gene 1.0 ST (Affymetrix) designed to measure gene expression of 28,869 well-annotated genes. A fixed fold-change cut-off corresponding to ± 2 was used to identify genes exhibiting the most significant variation and statistical significance (P< 0.05), and 8 genes validated by qPCR using Taqman probes. Conclusions 10 molecular processes were significantly affected in hVSMC: Apoptosis and cell cycle, extracellular matrix remodeling, DNA repair, cholesterol efflux, cGMP biosynthesis, endocytic mechanisms, calcium homeostasis, redox balance, membrane trafficking and finally, the immune response to inflammation. The evidence we present supporting the hypothesis for the involvement of oxidative modification of several processes and

  19. Human radiation studies: Remembering the early years: Oral history of pathologist Clarence Lushbaugh, M.D., conducted October 5, 1994

    SciTech Connect

    1995-04-01

    This report provides a transcript of an interview with Dr. Clarance Lushbaugh by representatives of the DOE Office of Human Radiation Experiments. Dr. Lushbaugh was chosen for this interview because of his research involving experimental use of irradiation with human beings at Los Alamos and at the Oak Ridge Institute of Nuclear Science (ORINS). After a brief biographical sketch Dr. Lushbaugh and his assistant Mrs. Ann Swipe defend their use of total body irradiation using the LETBI (Low Exposure Total Body Irradiation) and the LETBI (Medium Energy Total Body Irradiator). Dr. Lushbaugh also discusses his earlier experiments involving use of nitrogen mustards in chemotherapy application, his early interest in the LD50 for man, his early impressions of low-level spray radiation as introduced by Heubline, anedotal information for his duties a pathologist for Los Alamos, and his developing interest in establishing safer radiation limits for human exposure.

  20. Short adolescence in early hominids: infantile and adolescent growth of the human femur.

    PubMed

    Tardieu, C

    1998-10-01

    Did the first hominids have a short developmental period similar to that of the great apes or a longer period closer to that of modern humans? Evidence from studies on dental and facial growth favors the first point of view. Additional evidence presented in this report is provided by a morphogenetic analysis of the lower limb. Some morphological modifications undergone by the human femur during infantile and adolescent growth are shown to be excellent markers of different developmental stages. The angular remodelling of the femoral diaphysis, which results in femoral bicondylar angle, is a marker of infancy, while the reshaping of the distal femoral epiphysis is a marker of adolescence. This reshaping of the bony epiphysis consists of the strong projection of the external lip of the femoral trochlea, the increase of the radius of curvature of the external condyle, and the anteroposterior lengthening of the whole epiphysis. The growth spurt in linear dimensions of the femur, characteristic of human adolescence, is shown to be associated with qualitative changes of the distal femoral epiphysis engendered by the late closure of the distal epiphysis. The femur of the first hominids (Australopithecus afarensis) shows only features of infantile growth, whereas characters of both precocious and later growth are typical of later hominids (Homo). The absence of the derived epiphyseal features in Australopithecus would be linked to their early epiphyseal closure and short adolescent growth period; their presence in Homo would have been promoted by their delayed epiphyseal closure and prolonged adolescent growth period. The transition from Australopithecus to Homo appears to have involved a heterochronic process of time hypermorphosis (Gould, [1977], Ontogeny and Phylogeny [Cambridge: Harvard University Press]) in which the size of the femur increases, the epiphysis is modified, and the period of peripubertal growth is prolonged. The shape of the distal epiphyses of KNM

  1. Determinants of motion response anisotropies in human early visual cortex: the role of configuration and eccentricity.

    PubMed

    Maloney, Ryan T; Watson, Tamara L; Clifford, Colin W G

    2014-10-15

    Anisotropies in the cortical representation of various stimulus parameters can reveal the fundamental mechanisms by which sensory properties are analysed and coded by the brain. One example is the preference for motion radial to the point of fixation (i.e. centripetal or centrifugal) exhibited in mammalian visual cortex. In two experiments, this study used functional magnetic resonance imaging (fMRI) to explore the determinants of these radial biases for motion in functionally-defined areas of human early visual cortex, and in particular their dependence upon eccentricity which has been indicated in recent reports. In one experiment, the cortical response to wide-field random dot kinematograms forming 16 different complex motion patterns (including centrifugal, centripetal, rotational and spiral motion) was measured. The response was analysed according to preferred eccentricity within four different eccentricity ranges. Response anisotropies were characterised by enhanced activity for centripetal or centrifugal patterns that changed systematically with eccentricity in visual areas V1-V3 and hV4 (but not V3A/B or V5/MT+). Responses evolved from a preference for centrifugal over centripetal patterns close to the fovea, to a preference for centripetal over centrifugal at the most peripheral region stimulated, in agreement with previous work. These effects were strongest in V2 and V3. In a second experiment, the stimuli were restricted to within narrow annuli either close to the fovea (0.75-1.88°) or further in the periphery (4.82-6.28°), in a way that preserved the local motion information available in the first experiment. In this configuration a preference for radial motion (centripetal or centrifugal) persisted but the dependence upon eccentricity disappeared. Again this was clearest in V2 and V3. A novel interpretation of the dependence upon eccentricity of motion anisotropies in early visual cortex is offered that takes into account the spatiotemporal

  2. From Toumai to Lucy: climate and orographic forcing on Environment and Early Human

    NASA Astrophysics Data System (ADS)

    Ramstein, Gilles; Contoux, Camille; Sepulchre, Pierre; Schuster, Mathieu; Jost, Anne

    2014-05-01

    This abstract will present a summary of several studies we conducted at LSCE to understand through modeling simulations how the climate and topography variations may drive the evolution/migration of Early Humans. Tectonics and orbital forcing are major forcing factors on environment which act at different time scales. African Uplift spans over Millions of years whereas at low latitudes precession cycles will produce drastic hydrologic variations at the pluri millennial time scale. Therefore, in a first step it is necessary to investigate the impact of long term topographic changes on climate and vegetation. The long term forcing of the African uplift has been first tested and investigated through a set of numerical experiments using different heights for the Rift. We pointed out that this issue was the key factor to explain the dryness of the East part of the Rift associated with the disappearance of the forests when the rift was uplifted during the late Pliocene. Prior to this, much more water penetrates from the Indian Ocean over East Africa and forests can sustain. Therefore, this pattern of Dry East of the Rift and Wet west of the Rift is driven by the uplift and consistent with the evolution of vegetation. On the other side, the Mega Lake Chad (MLC) region was not really sensitive to this topographic change but much more to orbital forcing. Two species of early hominids (Australopithecus bahrelghazali, 3,6 Ma, and Sahelanthropus tchadensis, Toumai, 7 Ma) were found in this region, associated with other vertebrate fossil remains, which seem to be associated to the presence of the Mega Lake Chad. It is thus crucial to understand how it is possible to produce and sustain such a large lake (350 000 km2) at these latitudes. Through a second series of simulations, we demonstrated that during the Pliocene, occurrences of such megalake episodes were possible (similarly as during most recent Holocene) and may be sustained during half a precession cycle (10 kyr

  3. Early Pliocene hominids from Gona, Ethiopia.

    PubMed

    Semaw, Sileshi; Simpson, Scott W; Quade, Jay; Renne, Paul R; Butler, Robert F; McIntosh, William C; Levin, Naomi; Dominguez-Rodrigo, Manuel; Rogers, Michael J

    2005-01-20

    Comparative biomolecular studies suggest that the last common ancestor of humans and chimpanzees, our closest living relatives, lived during the Late Miocene-Early Pliocene. Fossil evidence of Late Miocene-Early Pliocene hominid evolution is rare and limited to a few sites in Ethiopia, Kenya and Chad. Here we report new Early Pliocene hominid discoveries and their palaeoenvironmental context from the fossiliferous deposits of As Duma, Gona Western Margin (GWM), Afar, Ethiopia. The hominid dental anatomy (occlusal enamel thickness, absolute and relative size of the first and second lower molar crowns, and premolar crown and radicular anatomy) indicates attribution to Ardipithecus ramidus. The combined radioisotopic and palaeomagnetic data suggest an age of between 4.51 and 4.32 million years for the hominid finds at As Duma. Diverse sources of data (sedimentology, faunal composition, ecomorphological variables and stable carbon isotopic evidence from the palaeosols and fossil tooth enamel) indicate that the Early Pliocene As Duma sediments sample a moderate rainfall woodland and woodland/grassland.

  4. Early Pliocene hominids from Gona, Ethiopia.

    PubMed

    Semaw, Sileshi; Simpson, Scott W; Quade, Jay; Renne, Paul R; Butler, Robert F; McIntosh, William C; Levin, Naomi; Dominguez-Rodrigo, Manuel; Rogers, Michael J

    2005-01-20

    Comparative biomolecular studies suggest that the last common ancestor of humans and chimpanzees, our closest living relatives, lived during the Late Miocene-Early Pliocene. Fossil evidence of Late Miocene-Early Pliocene hominid evolution is rare and limited to a few sites in Ethiopia, Kenya and Chad. Here we report new Early Pliocene hominid discoveries and their palaeoenvironmental context from the fossiliferous deposits of As Duma, Gona Western Margin (GWM), Afar, Ethiopia. The hominid dental anatomy (occlusal enamel thickness, absolute and relative size of the first and second lower molar crowns, and premolar crown and radicular anatomy) indicates attribution to Ardipithecus ramidus. The combined radioisotopic and palaeomagnetic data suggest an age of between 4.51 and 4.32 million years for the hominid finds at As Duma. Diverse sources of data (sedimentology, faunal composition, ecomorphological variables and stable carbon isotopic evidence from the palaeosols and fossil tooth enamel) indicate that the Early Pliocene As Duma sediments sample a moderate rainfall woodland and woodland/grassland. PMID:15662421

  5. Human exposure to early morning Anopheles funestus biting behavior and personal protection provided by long-lasting insecticidal nets.

    PubMed

    Moiroux, Nicolas; Damien, Georgia B; Egrot, Marc; Djenontin, Armel; Chandre, Fabrice; Corbel, Vincent; Killeen, Gerry F; Pennetier, Cédric

    2014-01-01

    A shift towards early morning biting behavior of the major malaria vector Anopheles funestus have been observed in two villages in south Benin following distribution of long-lasting insecticidal nets (LLINs), but the impact of these changes on the personal protection efficacy of LLINs was not evaluated. Data from human and An. funestus behavioral surveys were used to measure the human exposure to An. funestus bites through previously described mathematical models. We estimated the personal protection efficacy provided by LLINs and the proportions of exposure to bite occurring indoors and/or in the early morning. Average personal protection provided by using of LLIN was high (≥80% of the total exposure to bite), but for LLIN users, a large part of remaining exposure occurred outdoors (45.1% in Tokoli-V and 68.7% in Lokohoué) and/or in the early morning (38.5% in Tokoli-V and 69.4% in Lokohoué). This study highlights the crucial role of LLIN use and the possible need to develop new vector control strategies targeting malaria vectors with outdoor and early morning biting behavior. This multidisciplinary approach that supplements entomology with social science and mathematical modeling illustrates just how important it is to assess where and when humans are actually exposed to malaria vectors before vector control program managers, policy-makers and funders conclude what entomological observations imply.

  6. Palaeophylogenomics of the vertebrate ancestor--impact of hidden paralogy on hagfish and lamprey gene phylogeny.

    PubMed

    Kuraku, Shigehiro

    2010-07-01

    In dissecting the transition from invertebrates to vertebrates at the molecular level, whole-genome duplications are recognized as a key event. This gave rise to more copies of genes in jawed vertebrates (gnathostomes), such as the four Hox clusters in the human, compared to the single ancestral cluster in invertebrates. To date, as the most early-branching lineages in vertebrates, cyclostomes (hagfishes and lampreys) have been used for comparative analyses of gene regulations and functions. However, assignment of orthology/paralogy for cyclostomes' genes is not unambiguously demonstrated. Thus, there is a high degree of incongruence in tree topologies between gene families, although whole genome duplications postulate uniform patterns in gene phylogeny. In this review, we demonstrate how expansion of an ancient genome before the cyclostome-gnathostome split, followed by reciprocal gene loss, can cause this incongruence. This is sometimes referred to as 'hidden paralogy'. PMID:21558193

  7. Early-life disease exposure and associations with adult survival, cause of death, and reproductive success in preindustrial humans.

    PubMed

    Hayward, Adam D; Rigby, Francesca L; Lummaa, Virpi

    2016-08-01

    A leading hypothesis proposes that increased human life span since 1850 has resulted from decreased exposure to childhood infections, which has reduced chronic inflammation and later-life mortality rates, particularly from cardiovascular disease, stroke, and cancer. Early-life cohort mortality rate often predicts later-life survival in humans, but such associations could arise from factors other than disease exposure. Additionally, the impact of early-life disease exposure on reproduction remains unknown, and thus previous work ignores a major component of fitness through which selection acts upon life-history strategy. We collected data from seven 18th- and 19th-century Finnish populations experiencing naturally varying mortality and fertility levels. We quantified early-life disease exposure as the detrended child mortality rate from infectious diseases during an individual's first 5 y, controlling for important social factors. We found no support for an association between early-life disease exposure and all-cause mortality risk after age 15 or 50. We also found no link between early-life disease exposure and probability of death specifically from cardiovascular disease, stroke, or cancer. Independent of survival, there was no evidence to support associations between early-life disease exposure and any of several aspects of reproductive performance, including lifetime reproductive success and age at first birth, in either males or females. Our results do not support the prevailing assertion that exposure to infectious diseases in early life has long-lasting associations with later-life all-cause mortality risk or mortality putatively linked to chronic inflammation. Variation in adulthood conditions could therefore be the most likely source of recent increases in adult life span. PMID:27457937

  8. Early-life disease exposure and associations with adult survival, cause of death, and reproductive success in preindustrial humans.

    PubMed

    Hayward, Adam D; Rigby, Francesca L; Lummaa, Virpi

    2016-08-01

    A leading hypothesis proposes that increased human life span since 1850 has resulted from decreased exposure to childhood infections, which has reduced chronic inflammation and later-life mortality rates, particularly from cardiovascular disease, stroke, and cancer. Early-life cohort mortality rate often predicts later-life survival in humans, but such associations could arise from factors other than disease exposure. Additionally, the impact of early-life disease exposure on reproduction remains unknown, and thus previous work ignores a major component of fitness through which selection acts upon life-history strategy. We collected data from seven 18th- and 19th-century Finnish populations experiencing naturally varying mortality and fertility levels. We quantified early-life disease exposure as the detrended child mortality rate from infectious diseases during an individual's first 5 y, controlling for important social factors. We found no support for an association between early-life disease exposure and all-cause mortality risk after age 15 or 50. We also found no link between early-life disease exposure and probability of death specifically from cardiovascular disease, stroke, or cancer. Independent of survival, there was no evidence to support associations between early-life disease exposure and any of several aspects of reproductive performance, including lifetime reproductive success and age at first birth, in either males or females. Our results do not support the prevailing assertion that exposure to infectious diseases in early life has long-lasting associations with later-life all-cause mortality risk or mortality putatively linked to chronic inflammation. Variation in adulthood conditions could therefore be the most likely source of recent increases in adult life span.

  9. Specific interactions between transcription factors and the promoter-regulatory region of the human cytomegalovirus major immediate-early gene

    SciTech Connect

    Ghazal, P.; Lubon, H.; Hennighausen, L. )

    1988-03-01

    Repeat sequence motifs as well as unique sequences between nucleotides {minus}150 and {minus}22 of the human cytomegalovirus immediate-early 1 gene interact in vitro with nuclear proteins. The authors show that a transcriptional element between nucleotides {minus}91 and {minus}65 stimulated promoter activity in vivo and in vitro by binding specific cellular transcription factors. Finally, a common sequence motif, (T)TGG/AC, present in 15 of the determined binding sites suggests a particular class of nuclear factors associated with the immediate-early 1 gene.

  10. Cell-specific activity of the modulator region in the human cytomegalovirus major immediate-early gene

    SciTech Connect

    Lubon, H.K.; Hennighausen, L. ); Ghazal, P.; Reynolds-Kohler, C.; Lockshin, C.; Nelson, J. )

    1989-03-01

    In this paper the authors demonstrate that modular sequences upstream of the enhancer of the major immediate-early promoter of human cytomegalovirus exert a differential effort on the level of transcription in a variety of cells and that this region has the capacity to interact with specific nuclear protein. Depending on the cell type, these modulator sequences increased or decreased transcriptional activation from the IE1 gene promoter-enhancer. The cell lines identified in this report should be useful to study the molecular mechanism of cell-specific transcriptional repression and activation exerted by the major immediate-early promoter upstream region.

  11. Biomolecule-Mineral Interactions in the Geochemical Environment on Early Earth and in the Human Body

    NASA Astrophysics Data System (ADS)

    Sahai, N.

    2011-12-01

    We worked on four projects consistent with the broad goals of the grant to investigate (i) the potential impacts of mineral surface chemistry and particle size on the stability and viability of cell membranes, bacteria and human cells and (ii) the influence of biomolecules on mineral nucleation and growth. The projects are of relevance to the origin and early evolution of life, biomineralization, medical mineralogy, and environmental biogeochemistry. The freedom enabled by the five-year grant to explore high-risk scientific areas, and the resulting high impact outcomes, cannot be overstated. We developed an almost entirely new field of Medical Mineralogyy and extended our concepts and knowledge-base to the potential roles of mineral surfaces in the evolution of protocells and the earliest cells. These exciting connections to medical mineralogy, and to the origin and evolution of life on early Earth are fascinating topics to the general public and even to other scientists, especially when the links to mineralogy and geochemistry are highlighted. In brief, we examined the stability of lipid bilayers representing model protocell membranes comprised of phospholipid bilayers with mineral surfaces. We found that the stability of lipid bilayers depends on mineral surface charge and increases as silica glass ~ quartz < rutile ~ mica < corundum. In a second project, we investigated whether the evolution of bacterial extra-cellular polymeric substances (EPS) may have been driven by nanomineral toxicity. Results showed that EPS does protect against mineral toxicity, and toxicity increases as amorphous SiO2 < β-TiO2 (anatase) < γ-Al2O3. A commonly accepted mechanism for Biomineralization is protein-templated nucleation. We used Molecular Dynamics and Bioinformatics computational chemistry approaches and showed that the random coil structure of a specific peptide promotes formation of an amorphous Ca-PO4 cluster, but not direct templation of hydroxyapatite. The consistency

  12. Structure and transcription of an immediate-early region in the human herpesvirus 6 genome.

    PubMed Central

    Schiewe, U; Neipel, F; Schreiner, D; Fleckenstein, B

    1994-01-01

    The unique segment of the human herpesvirus 6 (HHV-6) genome is essentially collinear to the unique long DNA segment of another betaherpesvirus, the human cytomegalovirus (HCMV). However, the HHV-6 genomic section that is analogous in position to the major immediate-early (IE) locus of HCMV does not exhibit recognizable sequence homologies. The respective HHV-6 region of 5.5 kbp is flanked on one side by 25 to 28 incomplete tandem repeats of 105 to 110 bp that contain, with one exception, a single KpnI restriction site (KpnI repeats). About 250 reiterations of the sequence motif CACATA are located on the other end. We identified two open reading frames of 375 and 2,595 nucleotides, respectively, on one strand. Strand-specific Northern blot analyses with RNA harvested from HHV-6 (strain U1102)-infected HSB-2 cells or cord blood lymphocytes revealed two transcripts of about 3.5 and 4.7 kb in the corresponding orientation. Sequence analyses of the respective cDNA clones and primer extension experiments were used to map the mRNAs. The two transcripts are coterminal and multiply spliced and code for the same putative 104.6-kDa protein, but they are initiated from different promoters. Characterization of smaller cDNA clones and Northern blotting with other strand-specific probes showed that singly spliced mRNAs of 1.0 and 1.5 kb are transcribed from the opposite strand; they could code for a 17.2-kDa polypeptide. Blocking experiments with cycloheximide led to the conclusion that only the 3.5-kb mRNA is synthesized in the absence of protein biosynthesis upon infection with cell-free virus. This identifies a single IE gene of HHV-6 at the genomic position corresponding to the major IE region of HCMV, although the coding content and transcriptional regulation are quite different for these two herpesvirus IE regions. Images PMID:8151768

  13. Immunodetection of histone epitopes correlates with early stages of apoptosis in activated human peripheral T lymphocytes.

    PubMed Central

    Zunino, S. J.; Singh, M. K.; Bass, J.; Picker, L. J.

    1996-01-01

    By coupling intracellular staining with terminal deoxynucleotidyl transferase (TdT)-mediated labeling of internucleosomal DNA strand breaks in a flow cytometric assay, we observed a strong correlation between apoptosis-associated DNA strand breaks and immunoreactivity with the monoclonal antibody (MAb) B-F6 in activated human peripheral blood T lymphocytes (PBTs). Although MAb B-F6 has been reported to be specific for the cytokine interleukin-6, Western blot analysis of activated PBT lysates revealed that the predominant protein band detected by this MAb was 17 kd (p17), distinct from the 23-kd core protein and 26- to 30-kd mature glycosylated forms of interleukin-6. Immunoaffinity isolation and amino-terminal amino acid sequence analysis of p17 revealed identity with the histone H2B, a finding confirmed by Western blot analysis of purified histones and by similar staining of activated PBTs with an unrelated anti-histone MAb. Neither histone staining nor DNA strand breakage was observed in freshly isolated PBTs; however, after T cell activation, histone immunoreactivity appeared to precede the appearance of DNA strand breaks, with both increasing to a maximal level by day 3 after activation. Two-parameter confocal immunofluorescence microscopy of histone and DNA staining confirmed a lack of histone immunoreactivity in viable cells and demonstrated co-localization of histone epitopes with abnormally clumped chromatin in apoptotic cells. These data indicate that alteration of histone epitope accessibility is a marker of early apoptosis and suggest that multiparameter flow cytometric analysis of intracellular epitopes may be a powerful tool in the elucidation of intracellular mechanisms of apoptosis. Images Figure 4 Figure 5 Figure 6 Figure 8 PMID:8702003

  14. NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly of Human Complex I.

    PubMed

    Rhein, Virginie F; Carroll, Joe; Ding, Shujing; Fearnley, Ian M; Walker, John E

    2016-07-01

    Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 45 proteins. One arm lies in the inner membrane, and the other extends about 100 Å into the matrix of the organelle. The extrinsic arm contains binding sites for NADH, the primary electron acceptor FMN, and seven iron-sulfur clusters that form a pathway for electrons linking FMN to the terminal electron acceptor, ubiquinone, which is bound in a tunnel in the region of the junction between the arms. The membrane arm contains four antiporter-like domains, energetically coupled to the quinone site and involved in pumping protons from the matrix into the intermembrane space contributing to the proton motive force. Seven of the subunits, forming the core of the membrane arm, are translated from mitochondrial genes, and the remaining subunits, the products of nuclear genes, are imported from the cytosol. Their assembly is coordinated by at least thirteen extrinsic assembly factor proteins that are not part of the fully assembled complex. They assist in insertion of co-factors and in building up the complex from smaller sub-assemblies. One such factor, NDUFAF5, belongs to the family of seven-β-strand S-adenosylmethionine-dependent methyltransferases. However, similar to another family member, RdmB, it catalyzes the introduction of a hydroxyl group, in the case of NDUFAF5, into Arg-73 in the NDUFS7 subunit of human complex I. This modification occurs early in the pathway of assembly of complex I, before the formation of the juncture between peripheral and membrane arms. PMID:27226634

  15. NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly of Human Complex I.

    PubMed

    Rhein, Virginie F; Carroll, Joe; Ding, Shujing; Fearnley, Ian M; Walker, John E

    2016-07-01

    Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 45 proteins. One arm lies in the inner membrane, and the other extends about 100 Å into the matrix of the organelle. The extrinsic arm contains binding sites for NADH, the primary electron acceptor FMN, and seven iron-sulfur clusters that form a pathway for electrons linking FMN to the terminal electron acceptor, ubiquinone, which is bound in a tunnel in the region of the junction between the arms. The membrane arm contains four antiporter-like domains, energetically coupled to the quinone site and involved in pumping protons from the matrix into the intermembrane space contributing to the proton motive force. Seven of the subunits, forming the core of the membrane arm, are translated from mitochondrial genes, and the remaining subunits, the products of nuclear genes, are imported from the cytosol. Their assembly is coordinated by at least thirteen extrinsic assembly factor proteins that are not part of the fully assembled complex. They assist in insertion of co-factors and in building up the complex from smaller sub-assemblies. One such factor, NDUFAF5, belongs to the family of seven-β-strand S-adenosylmethionine-dependent methyltransferases. However, similar to another family member, RdmB, it catalyzes the introduction of a hydroxyl group, in the case of NDUFAF5, into Arg-73 in the NDUFS7 subunit of human complex I. This modification occurs early in the pathway of assembly of complex I, before the formation of the juncture between peripheral and membrane arms.

  16. Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer.

    PubMed

    Panis, C; Victorino, V J; Herrera, A C S A; Freitas, L F; De Rossi, T; Campos, F C; Simão, A N Colado; Barbosa, D S; Pinge-Filho, P; Cecchini, R; Cecchini, A L

    2012-06-01

    Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1β, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure

  17. NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly of Human Complex I*

    PubMed Central

    Rhein, Virginie F.; Carroll, Joe; Ding, Shujing; Fearnley, Ian M.; Walker, John E.

    2016-01-01

    Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 45 proteins. One arm lies in the inner membrane, and the other extends about 100 Å into the matrix of the organelle. The extrinsic arm contains binding sites for NADH, the primary electron acceptor FMN, and seven iron-sulfur clusters that form a pathway for electrons linking FMN to the terminal electron acceptor, ubiquinone, which is bound in a tunnel in the region of the junction between the arms. The membrane arm contains four antiporter-like domains, energetically coupled to the quinone site and involved in pumping protons from the matrix into the intermembrane space contributing to the proton motive force. Seven of the subunits, forming the core of the membrane arm, are translated from mitochondrial genes, and the remaining subunits, the products of nuclear genes, are imported from the cytosol. Their assembly is coordinated by at least thirteen extrinsic assembly factor proteins that are not part of the fully assembled complex. They assist in insertion of co-factors and in building up the complex from smaller sub-assemblies. One such factor, NDUFAF5, belongs to the family of seven-β-strand S-adenosylmethionine-dependent methyltransferases. However, similar to another family member, RdmB, it catalyzes the introduction of a hydroxyl group, in the case of NDUFAF5, into Arg-73 in the NDUFS7 subunit of human complex I. This modification occurs early in the pathway of assembly of complex I, before the formation of the juncture between peripheral and membrane arms. PMID:27226634

  18. Estimation of left ventricular operating stiffness from Doppler early filling deceleration time in humans

    NASA Technical Reports Server (NTRS)

    Garcia, M. J.; Firstenberg, M. S.; Greenberg, N. L.; Smedira, N.; Rodriguez, L.; Prior, D.; Thomas, J. D.

    2001-01-01

    Shortened early transmitral deceleration times (E(DT)) have been qualitatively associated with increased filling pressure and reduced survival in patients with cardiac disease and increased left ventricular operating stiffness (K(LV)). An equation relating K(LV) quantitatively to E(DT) has previously been described in a canine model but not in humans. During several varying hemodynamic conditions, we studied 18 patients undergoing open-heart surgery. Transesophageal echocardiographic two-dimensional volumes and Doppler flows were combined with high-fidelity left atrial (LA) and left ventricular (LV) pressures to determine K(LV). From digitized Doppler recordings, E(DT) was measured and compared against changes in LV and LA diastolic volumes and pressures. E(DT) (180 +/- 39 ms) was inversely associated with LV end-diastolic pressures (r = -0.56, P = 0.004) and net atrioventricular stiffness (r = -0.55, P = 0.006) but had its strongest association with K(LV) (r = -0.81, P < 0.001). K(LV) was predicted assuming a nonrestrictive orifice (K(nonrest)) from E(DT) as K(nonrest) = (0.07/E(DT))(2) with K(LV) = 1.01 K(nonrest) - 0.02; r = 0.86, P < 0.001, DeltaK (K(nonrest) - K(LV)) = 0.02 +/- 0.06 mm Hg/ml. In adults with cardiac disease, E(DT) provides an accurate estimate of LV operating stiffness and supports its application as a practical noninvasive index in the evaluation of diastolic function.

  19. A proposal of the proteome before the last universal common ancestor (LUCA)

    NASA Astrophysics Data System (ADS)

    de Farias, Sávio Torres; Rêgo, Thais Gaudêncio; José, Marco V.

    2016-01-01

    The search for understanding the biological nature of the last universal common ancestor (LUCA) has been a theoretical challenge and has sparked intense debate in the scientific community. We reconstructed the ancestral sequences of tRNAs in order to test the hypothesis that these molecules originated the first genes. The results showed that the proteome before LUCA may have been composed of basal energy metabolism, namely, compounds with three carbons in the glycolytic pathway, which operated as a distribution centre of substrates for the development of metabolic pathways of nucleotides, lipids and amino acids. Thus, we present a proposal for metabolism in organisms before LUCA that was the initial core for the assembly of further metabolic pathways.

  20. Age of the last common ancestor of extant Plasmodium parasite lineages.

    PubMed

    Hayakawa, Toshiyuki; Tachibana, Shin-Ichiro; Hikosaka, Kenji; Arisue, Nobuko; Matsui, Atsushi; Horii, Toshihiro; Tanabe, Kazuyuki

    2012-07-01

    Parasites of the genus Plasmodium infect all classes of amniotes (mammals, birds and reptiles) and display host specificity in their infections. It is therefore generally believed that Plasmodium parasites co-evolved intimately with their hosts. Here, we report that based on an evolutionary analysis using 22 genes in the nuclear genome, extant lineages of Plasmodium parasites originated roughly in the Oligocene epoch after the emergence of their hosts. This timing on the age of the common ancestor of extant Plasmodium parasites suggest the importance of host switches and lends support to the evolutionary scenario of a "malaria big bang" that was proposed based on the evolutionary analysis using the mitochondrial genome. PMID:22555021

  1. The genome sequences of Arachis duranensis and Arachis ipaensis, the diploid ancestors of cultivated peanut.

    PubMed

    Bertioli, David John; Cannon, Steven B; Froenicke, Lutz; Huang, Guodong; Farmer, Andrew D; Cannon, Ethalinda K S; Liu, Xin; Gao, Dongying; Clevenger, Josh; Dash, Sudhansu; Ren, Longhui; Moretzsohn, Márcio C; Shirasawa, Kenta; Huang, Wei; Vidigal, Bruna; Abernathy, Brian; Chu, Ye; Niederhuth, Chad E; Umale, Pooja; Araújo, Ana Cláudia G; Kozik, Alexander; Kim, Kyung Do; Burow, Mark D; Varshney, Rajeev K; Wang, Xingjun; Zhang, Xinyou; Barkley, Noelle; Guimarães, Patrícia M; Isobe, Sachiko; Guo, Baozhu; Liao, Boshou; Stalker, H Thomas; Schmitz, Robert J; Scheffler, Brian E; Leal-Bertioli, Soraya C M; Xun, Xu; Jackson, Scott A; Michelmore, Richard; Ozias-Akins, Peggy

    2016-04-01

    Cultivated peanut (Arachis hypogaea) is an allotetraploid with closely related subgenomes of a total size of ∼2.7 Gb. This makes the assembly of chromosomal pseudomolecules very challenging. As a foundation to understanding the genome of cultivated peanut, we report the genome sequences of its diploid ancestors (Arachis duranensis and Arachis ipaensis). We show that these genomes are similar to cultivated peanut's A and B subgenomes and use them to identify candidate disease resistance genes, to guide tetraploid transcript assemblies and to detect genetic exchange between cultivated peanut's subgenomes. On the basis of remarkably high DNA identity of the A. ipaensis genome and the B subgenome of cultivated peanut and biogeographic evidence, we conclude that A. ipaensis may be a direct descendant of the same population that contributed the B subgenome to cultivated peanut. PMID:26901068

  2. The genome sequences of Arachis duranensis and Arachis ipaensis, the diploid ancestors of cultivated peanut.

    PubMed

    Bertioli, David John; Cannon, Steven B; Froenicke, Lutz; Huang, Guodong; Farmer, Andrew D; Cannon, Ethalinda K S; Liu, Xin; Gao, Dongying; Clevenger, Josh; Dash, Sudhansu; Ren, Longhui; Moretzsohn, Márcio C; Shirasawa, Kenta; Huang, Wei; Vidigal, Bruna; Abernathy, Brian; Chu, Ye; Niederhuth, Chad E; Umale, Pooja; Araújo, Ana Cláudia G; Kozik, Alexander; Kim, Kyung Do; Burow, Mark D; Varshney, Rajeev K; Wang, Xingjun; Zhang, Xinyou; Barkley, Noelle; Guimarães, Patrícia M; Isobe, Sachiko; Guo, Baozhu; Liao, Boshou; Stalker, H Thomas; Schmitz, Robert J; Scheffler, Brian E; Leal-Bertioli, Soraya C M; Xun, Xu; Jackson, Scott A; Michelmore, Richard; Ozias-Akins, Peggy

    2016-04-01

    Cultivated peanut (Arachis hypogaea) is an allotetraploid with closely related subgenomes of a total size of ∼2.7 Gb. This makes the assembly of chromosomal pseudomolecules very challenging. As a foundation to understanding the genome of cultivated peanut, we report the genome sequences of its diploid ancestors (Arachis duranensis and Arachis ipaensis). We show that these genomes are similar to cultivated peanut's A and B subgenomes and use them to identify candidate disease resistance genes, to guide tetraploid transcript assemblies and to detect genetic exchange between cultivated peanut's subgenomes. On the basis of remarkably high DNA identity of the A. ipaensis genome and the B subgenome of cultivated peanut and biogeographic evidence, we conclude that A. ipaensis may be a direct descendant of the same population that contributed the B subgenome to cultivated peanut.

  3. Evidence of duplicated Hox genes in the most recent common ancestor of extant scorpions.

    PubMed

    Sharma, Prashant P; Santiago, Marc A; González-Santillán, Edmundo; Monod, Lionel; Wheeler, Ward C

    2015-01-01

    Scorpions (order Scorpiones) are unusual among arthropods, both for the extreme heteronomy of their bauplan and for the high gene family turnover exhibited in their genomes. These phenomena appear to be correlated, as two scorpion species have been shown to possess nearly twice the number of Hox genes present in most arthropods. Segmentally offset anterior expression boundaries of a subset of Hox paralogs have been shown to correspond to transitions in segmental identities in the scorpion posterior tagmata, suggesting that posterior heteronomy in scorpions may have been achieved by neofunctionalization of Hox paralogs. However, both the first scorpion genome sequenced and the developmental genetic data are based on exemplars of Buthidae, one of 19 families of scorpions. It is therefore not known whether Hox paralogy is limited to Buthidae or widespread among scorpions. We surveyed 24 high throughput transcriptomes and the single whole genome available for scorpions, in order to test the prediction that Hox gene duplications are common to the order. We used gene tree parsimony to infer whether the paralogy was consistent with a duplication event in the scorpion common ancestor. Here we show that duplicated Hox genes in non-buthid scorpions occur in six of the ten Hox classes. Gene tree topologies and parsimony-based reconciliation of the gene trees are consistent with a duplication event in the most recent common ancestor of scorpions. These results suggest that a Hox paralogy, and by extension the model of posterior patterning established in a buthid, can be extended to non-Buthidae scorpions. PMID:26492826

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

    PubMed Central

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

    2001-01-01

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

  5. The oldest known anthropoid postcranial fossils and the early evolution of higher primates.

    PubMed

    Gebo, D L; Dagosto, M; Beard, K C; Qi, T; Wang, J

    2000-03-16

    The middle Eocene primate family Eosimiidae, which is known from sites in central and eastern China and Myanmar, is central to efforts to reconstruct the origin and early evolution of anthropoid or 'higher' primates (monkeys, apes and humans). Previous knowledge of eosimiid anatomy has been restricted to the dentition and an isolated petrosal bone, and this limited anatomical information has led to conflicting interpretations of early anthropoid phylogeny. Here we describe foot bones of Eosimias from the same middle Eocene sites in China that yield abundant dental remains of this primate. Tarsals of Eosimias show derived anatomical traits that are otherwise restricted to living and fossil anthropoids. These new fossils substantiate the anthropoid status of Eosimias and clarify the phylogenetic position of anthropoids with respect to other major primate clades. Early anthropoids possessed a mosaic of primitive and derived traits in their postcranial skeletons, reflecting their derivation from haplorhine ancestors that retained many prosimian-like features.

  6. Educating Human Nature: "Nature" and "Nurture" in Early Confucian Moral Education

    ERIC Educational Resources Information Center

    Murray, Judson B.

    2012-01-01

    This study examines early Chinese moral education--its curriculum, objectives and the philosophical assumptions underlying them--in its classical Confucian expression. It analyzes early Confucian debates on moral psychology, the Confucian moral curriculum consisting of model emulation, cultural practices and canonical instruction, and the methods…

  7. Early brain development toward shaping of human mind: an integrative psychoneurodevelopmental model in prenatal and perinatal medicine.

    PubMed

    Hruby, Radovan; Maas, Lili M; Fedor-Freybergh, P G

    2013-01-01

    The article introduces an integrative psychoneurodevelopmental model of complex human brain and mind development based on the latest findings in prenatal and perinatal medicine in terms of integrative neuroscience. The human brain development is extraordinarily complex set of events and could be influenced by a lot of factors. It is supported by new insights into the early neuro-ontogenic processes with the help of structural 3D magnetic resonance imaging or diffusion tensor imaging of fetal human brain. Various factors and targets for neural development including birth weight variability, fetal and early-life programming, fetal neurobehavioral states and fetal behavioral responses to various stimuli and others are discussed. Molecular biology reveals increasing sets of genes families as well as transcription and neurotropic factors together with critical epigenetic mechanisms to be deeply employed in the crucial neurodevelopmental events. Another field of critical importance is psychoimmuno-neuroendocrinology. Various effects of glucocorticoids as well as other hormones, prenatal stress and fetal HPA axis modulation are thought to be of special importance for brain development. The early postnatal period is characterized by the next intense shaping of complex competences, induced mainly by the very unique mother - newborn´s interactions and bonding. All these mechanisms serve to shape individual human mind with complex abilities and neurobehavioral strategies. Continuous research elucidating these special competences of human fetus and newborn/child supports integrative neuroscientific approach to involve various scientific disciplines for the next progress in human brain and mind research, and opens new scientific challenges and philosophic attitudes. New findings and approaches in this field could establish new methods in science, in primary prevention and treatment strategies, and markedly contribute to the development of modern integrative and personalized

  8. Heritability and genetic correlations of fear-related behaviour in Red Junglefowl--possible implications for early domestication.

    PubMed

    Agnvall, Beatrix; Jöngren, Markus; Strandberg, Erling; Jensen, Per

    2012-01-01

    Domesticated species differ from their wild ancestors in a number of traits, generally referred to as the domesticated phenotype. Reduced fear of humans is assumed to have been an early prerequisite for the successful domestication of virtually all species. We hypothesized that fear of humans is linked to other domestication related traits. For three generations, we selected Red Junglefowl (ancestors of domestic chickens) solely on the reaction in a standardized Fear of Human-test. In this, the birds were exposed for a gradually approaching human, and their behaviour was continuously scored. This generated three groups of animals, high (H), low (L) and intermediate (I) fearful birds. The birds in each generation were additionally tested in a battery of behaviour tests, measuring aspects of fearfulness, exploration, and sociality. The results demonstrate that the variation in fear response of Red Junglefowl towards humans has a significant genetic component and is genetically correlated to behavioural responses in other contexts, of which some are associated with fearfulness and others with exploration. Hence, selection of Red Junglefowl on low fear for humans can be expected to lead to a correlated change of other behavioural traits over generations. It is therefore likely that domestication may have caused an initial suite of behavioural modifications, even without selection on anything besides tameness. PMID:22536354

  9. Heritability and genetic correlations of fear-related behaviour in Red Junglefowl--possible implications for early domestication.

    PubMed

    Agnvall, Beatrix; Jöngren, Markus; Strandberg, Erling; Jensen, Per

    2012-01-01

    Domesticated species differ from their wild ancestors in a number of traits, generally referred to as the domesticated phenotype. Reduced fear of humans is assumed to have been an early prerequisite for the successful domestication of virtually all species. We hypothesized that fear of humans is linked to other domestication related traits. For three generations, we selected Red Junglefowl (ancestors of domestic chickens) solely on the reaction in a standardized Fear of Human-test. In this, the birds were exposed for a gradually approaching human, and their behaviour was continuously scored. This generated three groups of animals, high (H), low (L) and intermediate (I) fearful birds. The birds in each generation were additionally tested in a battery of behaviour tests, measuring aspects of fearfulness, exploration, and sociality. The results demonstrate that the variation in fear response of Red Junglefowl towards humans has a significant genetic component and is genetically correlated to behavioural responses in other contexts, of which some are associated with fearfulness and others with exploration. Hence, selection of Red Junglefowl on low fear for humans can be expected to lead to a correlated change of other behavioural traits over generations. It is therefore likely that domestication may have caused an initial suite of behavioural modifications, even without selection on anything besides tameness.

  10. Early Impacts of a Human-in-the-Loop Evaluation in a Space Vehicle Mock-up Facility

    NASA Technical Reports Server (NTRS)

    Byrne, Vicky; Vos, Gordon; Whitmore, Mihriban

    2008-01-01

    The development of a new space vehicle, the Orion Crew Exploration Vehicle (CEV), provides Human Factors engineers an excellent opportunity to have an impact early in the design process. This case study highlights a Human-in-the-Loop (HITL) evaluation conducted in a Space Vehicle Mock-Up Facility and will describe the human-centered approach and how the findings are impacting design and operational concepts early in space vehicle design. The focus of this HITL evaluation centered on the activities that astronaut crewmembers would be expected to perform within the functional internal volume of the Crew Module (CM) of the space vehicle. The primary objective was to determine if there are aspects of a baseline vehicle configuration that would limit or prevent the performance of dynamically volume-driving activities (e.g. six crewmembers donning their suits in an evacuation scenario). A second objective was to step through concepts of operations for known systems and evaluate them in integrated scenarios. The functional volume for crewmember activities is closely tied to every aspect of system design (e.g. avionics, safety, stowage, seats, suits, and structural support placement). As this evaluation took place before the Preliminary Design Review of the space vehicle with some designs very early in the development, it was not meant to determine definitely that the crewmembers could complete every activity, but rather to provide inputs that could improve developing designs and concepts of operations definition refinement.

  11. Edaphics, active tectonics and animal movements in the Kenyan Rift - implications for early human evolution and dispersal

    NASA Astrophysics Data System (ADS)

    Kübler, Simon; Owenga, Peter; Rucina, Stephen; King, Geoffrey C. P.

    2014-05-01

    The quality of soils (edaphics) and the associated vegetation strongly controls the health of grazing animals. Until now, this has hardly been appreciated by paleo-anthropologists who only take into account the availability of water and vegetation in landscape reconstruction attempts. A lack of understanding the importance of the edaphics of a region greatly limits interpretations of the relation between our ancestors and animals over the last few million years. If a region lacks vital trace elements then wild grazing and browsing animals will avoid it and go to considerable length and take major risks to seek out better pasture. As a consequence animals must move around the landscape at different times of the year. In complex landscapes, such as tectonically active rifts, hominins can use advanced group behaviour to gain strategic advantage for hunting. Our study in the southern Kenya rift in the Lake Magadi region shows that the edaphics and active rift structures play a key role in present day animal movements as well as the for the location of an early hominin site at Mt. Olorgesailie. We carried out field analysis based on studying the relationship between the geology and soil development as well as the tectonic geomorphology to identify 'good' and 'bad' regions both in terms of edaphics and accessibility for grazing animals. We further sampled different soils that developed on the volcanic bedrock and sediment sources of the region and interviewed the local Maasai shepherds to learn about present-day good and bad grazing sites. At the Olorgesailie site the rift valley floor is covered with flood trachytes; basalts only occur at Mt. Olorgesailie and farther east up the rift flank. The hominin site is located in lacustrine sediments at the southern edge of a playa that extends north and northwest of Mt. Olorgesailie. The lakebeds are now tilted and eroded by motion on two north-south striking faults. The lake was trapped by basalt flows from Mt. Olorgesailie

  12. Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues.

    PubMed

    Thome, Joseph J C; Bickham, Kara L; Ohmura, Yoshiaki; Kubota, Masaru; Matsuoka, Nobuhide; Gordon, Claire; Granot, Tomer; Griesemer, Adam; Lerner, Harvey; Kato, Tomoaki; Farber, Donna L

    2016-01-01

    It is unclear how the immune response in early life becomes appropriately stimulated to provide protection while also avoiding excessive activation as a result of diverse new antigens. T cells are integral to adaptive immunity; mouse studies indicate that tissue localization of T cell subsets is important for both protective immunity and immunoregulation. In humans, however, the early development and function of T cells in tissues remain unexplored. We present here an analysis of lymphoid and mucosal tissue T cells derived from pediatric organ donors in the first two years of life, as compared to adult organ donors, revealing early compartmentalization of T cell differentiation and regulation. Whereas adult tissues contain a predominance of memory T cells, in pediatric blood and tissues the main subset consists of naive recent thymic emigrants, with effector memory T cells (T(EM)) found only in the lungs and small intestine. Additionally, regulatory T (T(reg)) cells comprise a high proportion (30-40%) of CD4(+) T cells in pediatric tissues but are present at much lower frequencies (1-10%) in adult tissues. Pediatric tissue T(reg) cells suppress endogenous T cell activation, and early T cell functionality is confined to the mucosal sites that have the lowest T(reg):T(EM) cell ratios, which suggests control in situ of immune responses in early life. PMID:26657141

  13. Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues.

    PubMed

    Thome, Joseph J C; Bickham, Kara L; Ohmura, Yoshiaki; Kubota, Masaru; Matsuoka, Nobuhide; Gordon, Claire; Granot, Tomer; Griesemer, Adam; Lerner, Harvey; Kato, Tomoaki; Farber, Donna L

    2016-01-01

    It is unclear how the immune response in early life becomes appropriately stimulated to provide protection while also avoiding excessive activation as a result of diverse new antigens. T cells are integral to adaptive immunity; mouse studies indicate that tissue localization of T cell subsets is important for both protective immunity and immunoregulation. In humans, however, the early development and function of T cells in tissues remain unexplored. We present here an analysis of lymphoid and mucosal tissue T cells derived from pediatric organ donors in the first two years of life, as compared to adult organ donors, revealing early compartmentalization of T cell differentiation and regulation. Whereas adult tissues contain a predominance of memory T cells, in pediatric blood and tissues the main subset consists of naive recent thymic emigrants, with effector memory T cells (T(EM)) found only in the lungs and small intestine. Additionally, regulatory T (T(reg)) cells comprise a high proportion (30-40%) of CD4(+) T cells in pediatric tissues but are present at much lower frequencies (1-10%) in adult tissues. Pediatric tissue T(reg) cells suppress endogenous T cell activation, and early T cell functionality is confined to the mucosal sites that have the lowest T(reg):T(EM) cell ratios, which suggests control in situ of immune responses in early life.

  14. Combined Genetic and Genealogic Studies Uncover a Large BAP1 Cancer Syndrome Kindred Tracing Back Nine Generations to a Common Ancestor from the 1700s.

    PubMed

    Carbone, Michele; Flores, Erin G; Emi, Mitsuru; Johnson, Todd A; Tsunoda, Tatsuhiko; Behner, Dusty; Hoffman, Harriet; Hesdorffer, Mary; Nasu, Masaki; Napolitano, Andrea; Powers, Amy; Minaai, Michael; Baumann, Francine; Bryant-Greenwood, Peter; Lauk, Olivia; Kirschner, Michaela B; Weder, Walter; Opitz, Isabelle; Pass, Harvey I; Gaudino, Giovanni; Pastorino, Sandra; Yang, Haining

    2015-12-01

    We recently discovered an inherited cancer syndrome caused by BRCA1-Associated Protein 1 (BAP1) germline mutations, with high incidence of mesothelioma, uveal melanoma and other cancers and very high penetrance by age 55. To identify families with the BAP1 cancer syndrome, we screened patients with family histories of multiple mesotheliomas and melanomas and/or multiple cancers. We identified four families that shared an identical BAP1 mutation: they lived across the US and did not appear to be related. By combining family histories, molecular genetics, and genealogical approaches, we uncovered a BAP1 cancer syndrome kindred of ~80,000 descendants with a core of 106 individuals, whose members descend from a couple born in Germany in the early 1700s who immigrated to North America. Their descendants spread throughout the country with mutation carriers affected by multiple malignancies. Our data show that, once a proband is identified, extended analyses of these kindreds, using genomic and genealogical studies to identify the most recent common ancestor, allow investigators to uncover additional branches of the family that may carry BAP1 mutations. Using this knowledge, we have identified new branches of this family carrying BAP1 mutations. We have also implemented early-detection strategies that help identify cancers at early-stage, when they can be cured (melanomas) or are more susceptible to therapy (MM and other malignancies). PMID:26683624

  15. When Humans Become Animals: Development of the Animal Category in Early Childhood

    ERIC Educational Resources Information Center

    Herrmann, Patricia A.; Medin, Douglas L.; Waxman, Sandra R.

    2012-01-01

    The current study examines 3- and 5-year-olds' representation of the concept we label "animal" and its two nested concepts--"animal"[subscript contrastive] (including only non-human animals) and "animal"[subscript inclusive] (including both humans and non-human animals). Building upon evidence that naming promotes object categorization, we…

  16. Comparative study of MSX-2, DLX-5, and DLX-7 gene expression during early human tooth development.

    PubMed

    Davideau, J L; Demri, P; Hotton, D; Gu, T T; MacDougall, M; Sharpe, P; Forest, N; Berdal, A

    1999-12-01

    Msx and Dlx family transcription factors are key elements of craniofacial development and act in specific combinations with growth factors to control the position and shape of various skeletal structures in mice. In humans, the mutations of MSX and DLX genes are associated with specific syndromes, such as tooth agenesis, craniosynostosis, and tricho-dento-osseous syndrome. To establish some relationships between those reported human syndromes, previous experimental data in mice, and the expression patterns of MSX and DLX homeogenes in the human dentition, we investigated MSX-2, DLX-5, and DLX-7 expression patterns and compared them in orofacial tissues of 7.5- to 9-wk-old human embryos by using in situ hybridization. Our data showed that MSX-2 was strongly expressed in the progenitor cells of human orofacial skeletal structures, including mandible and maxilla bones, Meckel's cartilage, and tooth germs, as shown for DLX-5. DLX-7 expression was restricted to the vestibular lamina and, later on, to the vestibular part of dental epithelium. The comparison of MSX-2, DLX-5, and DLX-7 expression patterns during the early stages of development of different human tooth types showed the existence of spatially ordered sequences of homeogene expression along the vestibular/lingual axis of dental epithelium. The expression of MSX-2 in enamel knot, as well as the coincident expression of MSX-2, DLX-5, and DLX-7 in a restricted vestibular area of dental epithelium, suggests the existence of various organizing centers involved in the control of human tooth morphogenesis.

  17. Changes of MR and DTI appearance in early human brain development

    NASA Astrophysics Data System (ADS)

    Marc, Cassian; Vachet, Clement; Gerig, Guido; Blocher, Joseph; Gilmore, John; Styner, Martin

    2010-03-01

    Understanding myelination in early brain development is of clinical importance, as many neurological disorders have their origin in early cerebral organization and maturation. The goal of this work is to study a large neonate database acquired with standard MR imagery to illuminate effects of early development in MRI. 90 neonates were selected from a study of healthy brain development. Subjects were imaged via MRI postnatally. MR acquisition included high-resolution structural and diffusion tensor images. Unbiased atlases for structural and DTI data were generated and co-registered into a single coordinate frame for voxel-wise comparison of MR and DTI appearance across time. All original datasets were mapped into this frame and structural image data was additionally intensity normalized. In addition, myelinated white matter probabilistic segmentations from our neonate tissue segmentation were mapped into the same space to study how our segmentation results were affected by the changing intensity characteristics in early development Linear regression maps and p-value maps were computed and visualized. The resulting visualization of voxelswise corresponding maps of all MR and DTI properties captures early development information in MR imagery. Surprisingly, we encountered regions of seemingly decreased myelinated WM probability over time even though we expected a confident increase for all of the brain. The intensity changes in the MR images in those regions help explain this counterintuitive result. The regressional results indicate that this is an effect of intensity changes due not solely to myelination processes but also likely brain dehydration processes in early postnatal development.

  18. Reexamining human origins in light of Ardipithecus ramidus.

    PubMed

    Lovejoy, C Owen

    2009-10-01

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

  19. Reexamining human origins in light of Ardipithecus ramidus.

    PubMed

    Lovejoy, C Owen

    2009-10-01

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

  20. The Last Universal Common Ancestor: emergence, constitution and genetic legacy of an elusive forerunner

    PubMed Central

    Glansdorff, Nicolas; Xu, Ying; Labedan, Bernard

    2008-01-01

    Background Since the reclassification of all life forms in three Domains (Archaea, Bacteria, Eukarya), the identity of their alleged forerunner (Last Universal Common Ancestor or LUCA) has been the subject of extensive controversies: progenote or already complex organism, prokaryote or protoeukaryote, thermophile or mesophile, product of a protracted progression from simple replicators to complex cells or born in the cradle of "catalytically closed" entities? We present a critical survey of the topic and suggest a scenario. Results LUCA does not appear to have been a simple, primitive, hyperthermophilic prokaryote but rather a complex community of protoeukaryotes with a RNA genome, adapted to a broad range of moderate temperatures, genetically redundant, morphologically and metabolically diverse. LUCA's genetic redundancy predicts loss of paralogous gene copies in divergent lineages to be a significant source of phylogenetic anomalies, i.e. instances where a protein tree departs from the SSU-rRNA genealogy; consequently, horizontal gene transfer may not have the rampant character assumed by many. Examining membrane lipids suggest LUCA had sn1,2 ester fatty acid lipids from which Archaea emerged from the outset as thermophilic by "thermoreduction," with a new type of membrane, composed of sn2,3 ether isoprenoid lipids; this occurred without major enzymatic reconversion. Bacteria emerged by reductive evolution from LUCA and some lineages further acquired extreme thermophily by convergent evolution. This scenario is compatible with the hypothesis that the RNA to DNA transition resulted from different viral invasions as proposed by Forterre. Beyond the controversy opposing "replication first" to metabolism first", the predictive arguments of theories on "catalytic closure" or "compositional heredity" heavily weigh in favour of LUCA's ancestors having emerged as complex, self-replicating entities from which a genetic code arose under natural selection. Conclusion Life

  1. The late Early Pleistocene human dental remains from Uadi Aalad and Mulhuli-Amo (Buia), Eritrean Danakil: macromorphology and microstructure.

    PubMed

    Zanolli, Clément; Bondioli, Luca; Coppa, Alfredo; Dean, Christopher M; Bayle, Priscilla; Candilio, Francesca; Capuani, Silvia; Dreossi, Diego; Fiore, Ivana; Frayer, David W; Libsekal, Yosief; Mancini, Lucia; Rook, Lorenzo; Medin Tekle, Tsegai; Tuniz, Claudio; Macchiarelli, Roberto

    2014-09-01

    Fieldwork performed during the last 15 years in various Early Pleistocene East African sites has significantly enlarged the fossil record of Homo erectus sensu lato (s.l.). Additional evidence comes from the Danakil Depression of Eritrea, where over 200 late Early to early Middle Pleistocene sites have been identified within a ∼1000 m-thick sedimentary succession outcropping in the Dandiero Rift Basin, near Buia. Along with an adult cranium (UA 31), which displays a blend of H. erectus-like and derived morpho-architectural features and three pelvic remains, two isolated permanent incisors (UA 222 and UA 369) have also been recovered from the 1 Ma (millions of years ago) Homo-bearing outcrop of Uadi Aalad. Since 2010, our surveys have expanded to the nearby (4.7 km) site of Mulhuli-Amo (MA). This is a fossiliferous area that has been preliminarily surveyed because of its exceptional concentration of Acheulean stone tools. So far, the site has yielded 10 human remains, including the unworn crown of a lower permanent molar (MA 93). Using diverse analytical tools (including high resolution μCT and μMRI), we analysed the external and internal macromorphology and microstructure of the three specimens, and whenever possible compared the results with similar evidence from early Homo, H. erectus s.l., H. antecessor, H. heidelbergensis (from North Africa), Neanderthals and modern humans. We also assessed the UA 369 lower incisor from Uadi Aalad for root completion timing and showed that it compares well with data for root apex closure in modern human populations. PMID:24852385

  2. The late Early Pleistocene human dental remains from Uadi Aalad and Mulhuli-Amo (Buia), Eritrean Danakil: macromorphology and microstructure.

    PubMed

    Zanolli, Clément; Bondioli, Luca; Coppa, Alfredo; Dean, Christopher M; Bayle, Priscilla; Candilio, Francesca; Capuani, Silvia; Dreossi, Diego; Fiore, Ivana; Frayer, David W; Libsekal, Yosief; Mancini, Lucia; Rook, Lorenzo; Medin Tekle, Tsegai; Tuniz, Claudio; Macchiarelli, Roberto

    2014-09-01

    Fieldwork performed during the last 15 years in various Early Pleistocene East African sites has significantly enlarged the fossil record of Homo erectus sensu lato (s.l.). Additional evidence comes from the Danakil Depression of Eritrea, where over 200 late Early to early Middle Pleistocene sites have been identified within a ∼1000 m-thick sedimentary succession outcropping in the Dandiero Rift Basin, near Buia. Along with an adult cranium (UA 31), which displays a blend of H. erectus-like and derived morpho-architectural features and three pelvic remains, two isolated permanent incisors (UA 222 and UA 369) have also been recovered from the 1 Ma (millions of years ago) Homo-bearing outcrop of Uadi Aalad. Since 2010, our surveys have expanded to the nearby (4.7 km) site of Mulhuli-Amo (MA). This is a fossiliferous area that has been preliminarily surveyed because of its exceptional concentration of Acheulean stone tools. So far, the site has yielded 10 human remains, including the unworn crown of a lower permanent molar (MA 93). Using diverse analytical tools (including high resolution μCT and μMRI), we analysed the external and internal macromorphology and microstructure of the three specimens, and whenever possible compared the results with similar evidence from early Homo, H. erectus s.l., H. antecessor, H. heidelbergensis (from North Africa), Neanderthals and modern humans. We also assessed the UA 369 lower incisor from Uadi Aalad for root completion timing and showed that it compares well with data for root apex closure in modern human populations.

  3. Single, ancient origin of a plastid metabolite translocator family in Plantae from an endomembrane-derived ancestor.

    PubMed

    Weber, Andreas P M; Linka, Marc; Bhattacharya, Debashish

    2006-03-01

    Phylogenetic analyses show the single origin of a plastid metabolite translocator family in the Plantae from a gene encoding an existing endomembrane-derived protein. Red algal secondary endosymbiosis has spread a translocator gene into the ancestor of the "chromalveolate" protists, where it has diversified into a novel clade of proteins.

  4. Protein Export Marks the Early Phase of Gametocytogenesis of the Human Malaria Parasite Plasmodium falciparum*

    PubMed Central

    Silvestrini, Francesco; Lasonder, Edwin; Olivieri, Anna; Camarda, Grazia; van Schaijk, Ben; Sanchez, Massimo; Younis Younis, Sumera; Sauerwein, Robert; Alano, Pietro

    2010-01-01

    Despite over a century of study of malaria parasites, parts of the Plasmodium falciparum life cycle remain virtually unknown. One of these is the early gametocyte stage, a round shaped cell morphologically similar to an asexual trophozoite in which major cellular transformations ensure subsequent development of the elongated gametocyte. We developed a protocol to obtain for the first time highly purified preparations of early gametocytes using a transgenic line expressing a green fluorescent protein from the onset of gametocytogenesis. We determined the cellular proteome (1427 proteins) of this parasite stage by high accuracy tandem mass spectrometry and newly determined the proteomes of asexual trophozoites and mature gametocytes, identifying altogether 1090 previously undetected parasite proteins. Quantitative label-free comparative proteomics analysis determined enriched protein clusters for the three parasite developmental stages. Gene set enrichment analysis on the 251 proteins enriched in the early gametocyte proteome revealed that proteins putatively exported and involved in erythrocyte remodeling are the most overrepresented protein set in these stages. One-tenth of the early gametocyte-enriched proteome is constituted of putatively exported proteins, here named PfGEXPs (P. falciparum gametocyte-exported proteins). N-terminal processing and N-acetylation at a conserved leucine residue within the Plasmodium export element pentamotif were detected by mass spectrometry for three such proteins in the early but not in the mature gametocyte sample, further supporting a specific role in protein export in early gametocytogenesis. Previous reports and results of our experiments confirm that the three proteins are indeed exported in the erythrocyte cytoplasm. This work indicates that protein export profoundly marks early sexual differentiation in P. falciparum, probably contributing to host cell remodeling in this phase of the life cycle, and that gametocyte

  5. Neurobiological consequences of early stress and childhood maltreatment: are results from human and animal studies comparable?

    PubMed

    Teicher, Martin H; Tomoda, Akemi; Andersen, Susan L

    2006-07-01

    Recent studies have reported an association between exposure to childhood abuse or neglect and alterations in brain structure or function. One limitation of these studies is that they are correlational and do not provide evidence of a cause-effect relationship. Preclinical studies on the effects of exposure to early life stress can demonstrate causality, and can enrich our understanding of the clinical research if we hypothesize that the consequences of early abuse are predominantly mediated through the induction of stress responses. Exposure to early abuse and early stress has each been associated with the emergence of epileptiform electroencephalogram (EEG) abnormalities, alterations in corpus callosum area, and reduced volume or synaptic density of the hippocampus. Further, there is evidence that different brain regions have unique periods when they are maximally sensitive to the effects of early stress. To date, preclinical studies have guided clinical investigations and will continue to provide important insight into studies on molecular mechanisms and gene-environment interactions. PMID:16891580

  6. When humans become animals: Development of the animal category in early childhood.

    PubMed

    Herrmann, Patricia A; Medin, Douglas L; Waxman, Sandra R

    2012-01-01

    The current study examines 3- and 5-year-olds' representation of the concept we label 'animal' and its two nested concepts -animal(contrastive) (including only non-human animals) and animal(inclusive) (including both humans and non-human animals). Building upon evidence that naming promotes object categorization, we introduced a novel noun for two distinct objects, and analyzed children's patterns of extension. In Experiment 1, children heard a novel noun in conjunction with two non-human animals (dog, bird). Here, both 3- and 5-year-olds readily accessed animal(contrastive) and extended the noun systematically to other (previously un-named) non-human animals. In Experiment 2, children heard a novel noun in conjunction with a human and non-human animal. Here, 5-year-olds (but not 3-year-olds) accessed animal(inclusive) and extended the noun systematically to humans and non-human animals. These results underscore the developmental challenge facing young children as they identify the scope of the fundamental biological term 'animal' and its corresponding, nested concept(s).

  7. Membrane heredity and early chloroplast evolution.

    PubMed

    Cavalier-Smith, T

    2000-04-01

    Membrane heredity was central to the unique symbiogenetic origin from cyanobacteria of chloroplasts in the ancestor of Plantae (green plants, red algae, glaucophytes) and to subsequent lateral transfers of plastids to form even more complex photosynthetic chimeras. Each symbiogenesis integrated disparate genomes and several radically different genetic membranes into a more complex cell. The common ancestor of Plantae evolved transit machinery for plastid protein import. In later secondary symbiogeneses, signal sequences were added to target proteins across host perialgal membranes: independently into green algal plastids (euglenoids, chlorarachneans) and red algal plastids (alveolates, chromists). Conservatism and innovation during early plastid diversification are discussed.

  8. Fossils, feet and the evolution of human bipedal locomotion.

    PubMed

    Harcourt-Smith, W E H; Aiello, L C

    2004-05-01

    We review the evolution of human bipedal locomotion with a particular emphasis on the evolution of the foot. We begin in the early twentieth century and focus particularly on hypotheses of an ape-like ancestor for humans and human bipedal locomotion put forward by a succession of Gregory, Keith, Morton and Schultz. We give consideration to Morton's (1935) synthesis of foot evolution, in which he argues that the foot of the common ancestor of modern humans and the African apes would be intermediate between the foot of Pan and Hylobates whereas the foot of a hypothetical early hominin would be intermediate between that of a gorilla and a modern human. From this base rooted in comparative anatomy of living primates we trace changing ideas about the evolution of human bipedalism as increasing amounts of postcranial fossil material were discovered. Attention is given to the work of John Napier and John Robinson who were pioneers in the interpretation of Plio-Pleistocene hominin skeletons in the 1960s. This is the period when the wealth of evidence from the southern African australopithecine sites was beginning to be appreciated and Olduvai Gorge was revealing its first evidence for Homo habilis. In more recent years, the discovery of the Laetoli footprint trail, the AL 288-1 (A. afarensis) skeleton, the wealth of postcranial material from Koobi Fora, the Nariokotome Homo ergaster skeleton, Little Foot (Stw 573) from Sterkfontein in South Africa, and more recently tantalizing material assigned to the new and very early taxa Orrorin tugenensis, Ardipithecus ramidus and Sahelanthropus tchadensis has fuelled debate and speculation. The varying interpretations based on this material, together with changing theoretical insights and analytical approaches, is discussed and assessed in the context of new three-dimensional morphometric analyses of australopithecine and Homo foot bones, suggesting that there may have been greater diversity in human bipedalism in the earlier phases

  9. Fossils, feet and the evolution of human bipedal locomotion.

    PubMed

    Harcourt-Smith, W E H; Aiello, L C

    2004-05-01

    We review the evolution of human bipedal locomotion with a particular emphasis on the evolution of the foot. We begin in the early twentieth century and focus particularly on hypotheses of an ape-like ancestor for humans and human bipedal locomotion put forward by a succession of Gregory, Keith, Morton and Schultz. We give consideration to Morton's (1935) synthesis of foot evolution, in which he argues that the foot of the common ancestor of modern humans and the African apes would be intermediate between the foot of Pan and Hylobates whereas the foot of a hypothetical early hominin would be intermediate between that of a gorilla and a modern human. From this base rooted in comparative anatomy of living primates we trace changing ideas about the evolution of human bipedalism as increasing amounts of postcranial fossil material were discovered. Attention is given to the work of John Napier and John Robinson who were pioneers in the interpretation of Plio-Pleistocene hominin skeletons in the 1960s. This is the period when the wealth of evidence from the southern African australopithecine sites was beginning to be appreciated and Olduvai Gorge was revealing its first evidence for Homo habilis. In more recent years, the discovery of the Laetoli footprint trail, the AL 288-1 (A. afarensis) skeleton, the wealth of postcranial material from Koobi Fora, the Nariokotome Homo ergaster skeleton, Little Foot (Stw 573) from Sterkfontein in South Africa, and more recently tantalizing material assigned to the new and very early taxa Orrorin tugenensis, Ardipithecus ramidus and Sahelanthropus tchadensis has fuelled debate and speculation. The varying interpretations based on this material, together with changing theoretical insights and analytical approaches, is discussed and assessed in the context of new three-dimensional morphometric analyses of australopithecine and Homo foot bones, suggesting that there may have been greater diversity in human bipedalism in the earlier phases

  10. Fossils, feet and the evolution of human bipedal locomotion

    PubMed Central

    Harcourt-Smith, W E H; Aiello, L C

    2004-01-01

    We review the evolution of human bipedal locomotion with a particular emphasis on the evolution of the foot. We begin in the early twentieth century and focus particularly on hypotheses of an ape-like ancestor for humans and human bipedal locomotion put forward by a succession of Gregory, Keith, Morton and Schultz. We give consideration to Morton's (1935) synthesis of foot evolution, in which he argues that the foot of the common ancestor of modern humans and the African apes would be intermediate between the foot of Pan and Hylobates whereas the foot of a hypothetical early hominin would be intermediate between that of a gorilla and a modern human. From this base rooted in comparative anatomy of living primates we trace changing ideas about the evolution of human bipedalism as increasing amounts of postcranial fossil material were discovered. Attention is given to the work of John Napier and John Robinson who were pioneers in the interpretation of Plio-Pleistocene hominin skeletons in the 1960s. This is the period when the wealth of evidence from the southern African australopithecine sites was beginning to be appreciated and Olduvai Gorge was revealing its first evidence for Homo habilis. In more recent years, the discovery of the Laetoli footprint trail, the AL 288-1 (A. afarensis) skeleton, the wealth of postcranial material from Koobi Fora, the Nariokotome Homo ergaster skeleton, Little Foot (Stw 573) from Sterkfontein in South Africa, and more recently tantalizing material assigned to the new and very early taxa Orrorin tugenensis, Ardipithecus ramidus and Sahelanthropus tchadensis has fuelled debate and speculation. The varying interpretations based on this material, together with changing theoretical insights and analytical approaches, is discussed and assessed in the context of new three-dimensional morphometric analyses of australopithecine and Homo foot bones, suggesting that there may have been greater diversity in human bipedalism in the earlier phases

  11. Indian Hedgehog in Synovial Fluid Is a Novel Marker for Early Cartilage Lesions in Human Knee Joint

    PubMed Central

    Zhang, Congming; Wei, Xiaochun; Chen, Chongwei; Cao, Kun; Li, Yongping; Jiao, Qiang; Ding, Juan; Zhou, Jingming; Fleming, Braden C.; Chen, Qian; Shang, Xianwen; Wei, Lei

    2014-01-01

    To determine whether there is a correlation between the concentration of Indian hedgehog (Ihh) in synovial fluid (SF) and the severity of cartilage damage in the human knee joints, the knee cartilages from patients were classified using the Outer-bridge scoring system and graded using the Modified Mankin score. Expression of Ihh in cartilage and SF samples were analyzed with immunohistochemistry (IHC), western blot, and enzyme-linked immunosorbent assay (ELISA). Furthermore, we detected and compared Ihh protein levels in rat and mice cartilages between normal control and surgery-induced osteoarthritis (OA) group by IHC and fluorescence molecular tomography in vivo respectively. Ihh expression was increased 5.2-fold in OA cartilage, 3.1-fold in relative normal OA cartilage, and 1.71-fold in OA SF compared to normal control samples. The concentrations of Ihh in cartilage and SF samples was significantly increased in early-stage OA samples when compared to normal samples (r = 0.556; p < 0.001); however, there were no significant differences between normal samples and late-stage OA samples. Up-regulation of Ihh protein was also an early event in the surgery-induced OA models. Increased Ihh is associated with the severity of OA cartilage damage. Elevated Ihh content in human knee joint synovial fluid correlates with early cartilage lesions. PMID:24786088

  12. Interactions between climate change and human activities during the early to mid-Holocene in the eastern Mediterranean basins

    NASA Astrophysics Data System (ADS)

    Berger, Jean-Francois; Lespez, Laurent; Kuzucuoğlu, Catherine; Glais, Arthur; Hourani, Fuad; Barra, Adrien; Guilaine, Jean

    2016-09-01

    This paper focuses on early Holocene rapid climate change (RCC) records in the Mediterranean zone, which are under-represented in continental archives (9.2 to 8.2 ka events) and on their impact on prehistoric societies. This lack of data handicaps the general interpretation of climate impacts on human societies, which flourished in recent years. Key questions remain about the impact of early Holocene cooling events on the Mediterranean climate, ecosystems and human societies. In this paper, we discuss some examples from river and lake systems from the eastern to central Mediterranean area (central Anatolia, Cyprus, northeastern and northwestern Greece) that illustrate some palaeohydrological and erosion variations that modified the sustainability of the first Neolithic populations in this region. Results allow us to present direct land-sea correlations and to reconstruct regional long-term trends as well as millennial- to centennial-scale climatic changes. In this context, we question the socio-economic and geographical adaptation capacities of these societies (mobility, technology, economic practices, social organisation) during the "early Holocene" interval (11.7 to 8.2 ka), which corresponds partly to the Sapropel 1 deposition in the eastern Mediterranean sea.

  13. The Early Middle Palaeolithic in Britain: archaeology, settlement history and human behaviour

    NASA Astrophysics Data System (ADS)

    White, Mark; Scott, Beccy; Ashton, Nick

    2006-07-01

    A number of archaeological sites dated to MIS 8 and MIS 7 and containing Early Middle Palaeolithic Levalloisian assemblages can now be identified within the British Palaeolithic record. These provide a mixture of high- and low-resolution signatures, which together permit the reconstruction of aspects of early Neanderthal behaviour, settlement history and technological organisation within the British Isles. Much is certainly missing, but it is now possible to begin the task of disentangling the previously conflated Middle Palaeolithic, separating those sites belonging to the Middle Pleistocene from those dating to the last climatic cycle. This paper presents the first attempt to synthesise the data from the Early Middle Palaeolithic and presents some of our preliminary and tentatively held interpretations of what it might mean. Copyright

  14. Polyploids with different origins and ancestors form a single sexual polyploid species.

    PubMed

    Holloway, Alisha K; Cannatella, David C; Gerhardt, H Carl; Hillis, David M

    2006-04-01

    Polyploidization is one of the few mechanisms that can produce instantaneous speciation. Multiple origins of tetraploid lineages from the same two diploid progenitors are common, but here we report the first known instance of a single tetraploid species that originated repeatedly from at least three diploid ancestors. Parallel evolution of advertisement calls in tetraploid lineages of gray tree frogs has allowed these lineages to interbreed, resulting in a single sexually interacting polyploid species despite the separate origins of polyploids from different diploids. Speciation by polyploidization in these frogs has been the source of considerable debate, but the various published hypotheses have assumed that polyploids arose through either autopolyploidy or allopolyploidy of extant diploid species. We utilized molecular markers and advertisement calls to infer the origins of tetraploid gray tree frogs. Previous hypotheses did not sufficiently account for the observed data. Instead, we found that tetraploids originated multiple times from extant diploid gray tree frogs and two other, apparently extinct, lineages of tree frogs. Tetraploid lineages then merged through interbreeding to result in a single species. Thus, polyploid species may have complex origins, especially in systems in which isolating mechanisms (such as advertisement calls) are affected directly through hybridization and polyploidy. PMID:16670990

  15. How Old Is the Most Recent Ancestor of Two Copies of an Allele?

    PubMed Central

    Patterson, Nick J.

    2005-01-01

    An important clue to the evolutionary history of an allele is the structure of the neighboring region of the genome, which we term the genomic background of the allele. Consider two copies of the allele. How similar we expect their genomic background to be is strongly influenced by the age of their most recent common ancestor (MRCA). We apply diffusion theory, first used by Motoo Kimura as a tool for predicting the changes in allele frequencies over time and developed by him in many articles in this journal, to prove a variety of new results on the age of the MRCA under the simplest demographic assumptions. In particular, we show that the expected age of the MRCA of two copies of an allele with population frequency f is just 2Nf generations, where N is the effective population size. Our results are a first step in running exact coalescent simulations, where we also simulate the history of the population frequency of an allele. PMID:15520271

  16. Structural Similarities between Thiamin-Binding Protein and Thiaminase-I Suggest a Common Ancestor

    SciTech Connect

    Soriano, Erika V.; Rajashankar, Kanagalaghatta R.; Hanes, Jeremiah W.; Bale, Shridhar; Begley, Tadhg P.; Ealick, Steven E.

    2008-06-30

    ATP-binding cassette (ABC) transporters are responsible for the transport of a wide variety of water-soluble molecules and ions into prokaryotic cells. In Gram-negative bacteria, periplasmic-binding proteins deliver ions or molecules such as thiamin to the membrane-bound ABC transporter. The gene for the thiamin-binding protein tbpA has been identified in both Escherichia coli and Salmonella typhimurium. Here we report the crystal structure of TbpA from E. coli with bound thiamin monophosphate. The structure was determined at 2.25 {angstrom} resolution using single-wavelength anomalous diffraction experiments, despite the presence of nonmerohedral twinning. The crystal structure shows that TbpA belongs to the group II periplasmic-binding protein family. Equilibrium binding measurements showed similar dissociation constants for thiamin, thiamin monophosphate, and thiamin pyrophosphate. Analysis of the binding site by molecular modeling demonstrated how TbpA binds all three forms of thiamin. A comparison of TbpA and thiaminase-I, a thiamin-degrading enzyme, revealed structural similarity between the two proteins, especially in domain 1, suggesting that the two proteins evolved from a common ancestor.

  17. Structural similarities between thiamin-binding protein and thiaminase-I suggest a common ancestor.

    PubMed

    Soriano, Erika V; Rajashankar, Kanagalaghatta R; Hanes, Jeremiah W; Bale, Shridhar; Begley, Tadhg P; Ealick, Steven E

    2008-02-01

    ATP-binding cassette (ABC) transporters are responsible for the transport of a wide variety of water-soluble molecules and ions into prokaryotic cells. In Gram-negative bacteria, periplasmic-binding proteins deliver ions or molecules such as thiamin to the membrane-bound ABC transporter. The gene for the thiamin-binding protein tbpA has been identified in both Escherichia coli and Salmonella typhimurium. Here we report the crystal structure of TbpA from E. coli with bound thiamin monophosphate. The structure was determined at 2.25 A resolution using single-wavelength anomalous diffraction experiments, despite the presence of nonmerohedral twinning. The crystal structure shows that TbpA belongs to the group II periplasmic-binding protein family. Equilibrium binding measurements showed similar dissociation constants for thiamin, thiamin monophosphate, and thiamin pyrophosphate. Analysis of the binding site by molecular modeling demonstrated how TbpA binds all three forms of thiamin. A comparison of TbpA and thiaminase-I, a thiamin-degrading enzyme, revealed structural similarity between the two proteins, especially in domain 1, suggesting that the two proteins evolved from a common ancestor.

  18. The Time to Most Recent Common Ancestor Does Not (Usually) Approximate the Date of Divergence.

    PubMed

    Pettengill, James B

    2015-01-01

    With the advent of more sophisticated models and increase in computational power, an ever-growing amount of information can be extracted from DNA sequence data. In particular, recent advances have allowed researchers to estimate the date of historical events for a group of interest including time to most recent common ancestor (TMRCA), dates of specific nodes in a phylogeny, and the date of divergence or speciation date. Here I use coalescent simulations and re-analyze an empirical dataset to illustrate the importance of taxon sampling, in particular, on correctly estimating such dates. I show that TMRCA of representatives of a single taxon is often not the same as divergence date due to issues such as incomplete lineage sorting. Of critical importance is when estimating divergence or speciation dates a representative from a different taxonomic lineage must be included in the analysis. Without considering these issues, studies may incorrectly estimate the times at which historical events occurred, which has profound impacts within both research and applied (e.g., those related to public health) settings.

  19. Hybrid apomicts trapped in the ecological niches of their sexual ancestors

    PubMed Central

    Mau, Martin; Lovell, John T.; Corral, José M.; Kiefer, Christiane; Koch, Marcus A.; Aliyu, Olawale M.; Sharbel, Timothy F.

    2015-01-01

    Asexual reproduction is expected to reduce the adaptive potential to novel or changing environmental conditions, restricting or altering the ecological niche of asexual lineages. Asexual lineages of plants and animals are typically polyploid, an attribute that may influence their genetic variation, plasticity, adaptive potential, and niche breadth. The genus Boechera (Brassicaceae) represents an ideal model to test the relative ecological and biogeographic impacts of reproductive mode and ploidy because it is composed of diploid sexual and both diploid and polyploid asexual (i.e., apomictic) lineages. Here, we demonstrate a strong association between a transcriptionally conserved allele and apomictic seed formation. We then use this allele as a proxy apomixis marker in 1,649 accessions to demonstrate that apomixis is likely to be a common feature across the Boechera phylogeny. Phylogeographic analyses of these data demonstrate (i) species-specific niche differentiation in sexuals, (ii) extensive niche conservation between differing reproductive modes of the same species, (iii) ploidy-specific niche differentiation within and among species, and (iv) occasional niche drift between apomicts and their sexual ancestors. We conclude that ploidy is a substantially stronger and more common driver of niche divergence within and across Boechera species although variation in both traits may not necessarily lead to niche evolution on the species scale. PMID:25902513

  20. Ascomatal morphogenesis in Myxotrichum arcticum supports the derivation of the Myxotrichaceae from a discomycetous ancestor.

    PubMed

    Tsuneda, A; Currah, R S

    2004-01-01

    Electron microscopy shows that ascomata of Myxotricum arcticum bear a striking resemblance to discocarps in morphogenesis and in previously overlooked aspects of gross morphology. Although mature ascomata of M. arcticum superficially resemble reticuloperidial cleistothecia common in the Onygenales, the bramble-like aggregation of thick-walled hyphae, previously considered to represent a closed peridium, forms a basket-like apothecium that overarches a distinct hymenium of stipitate, protunicate asci interspersed with paraphyses. There is no evidence of asci developing in chains and at different levels as is characteristic of the centrum of many Eurotiomycetes. Instead, more or less globose, stipitate and evanescent asci arise individually from penultimate cells of croziers and develop almost synchronously across a distinct hymenial layer derived from a richly branched network of crozier-bearing hyphae. After dissolution of the ascus wall, ascospores adhere to a membranous sheath that underlies the hymenium. These observations provide strong support for prior suggestions based on molecular phylogenetic comparisons that the Myxotrichaceae recently are derived from a helotialean ancestor. Observations of conidiogenesis show that the typical Oidiodendron anamorph is accompanied by a second conidiogenous form with ampullae and botryose clusters of blastic conidia. PMID:21148882

  1. Wild mallards have more "goose-like" bills than their ancestors: a case of anthropogenic influence?

    PubMed

    Söderquist, Pär; Norrström, Joanna; Elmberg, Johan; Guillemain, Matthieu; Gunnarsson, Gunnar

    2014-01-01

    Wild populations of the world's most common dabbling duck, the mallard (Anas platyrhynchos), run the risk of genetic introgression by farmed conspecifics released for hunting purposes. We tested whether bill morphology of free-living birds has changed since large-scale releases of farmed mallards started. Three groups of mallards from Sweden, Norway and Finland were compared: historical wild (before large-scale releases started), present-day wild, and present-day farmed. Higher density of bill lamellae was observed in historical wild mallards (only males). Farmed mallards had wider bills than present-day and historical wild ones. Present-day wild and farmed mallards also had higher and shorter bills than historical wild mallards. Present-day mallards thus tend to have more "goose-like" bills (wider, higher, and shorter) than their ancestors. Our study suggests that surviving released mallards affect morphological traits in wild population by introgression. We discuss how such anthropogenic impact may lead to a maladapted and genetically compromised wild mallard population. Our study system has bearing on other taxa where large-scale releases of conspecifics with 'alien genes' may cause a cryptic invasive process that nevertheless has fitness consequences for individual birds. PMID:25514789

  2. Convergent evolution of Hawaiian and Australo-Pacific honeyeaters from distant songbird ancestors.

    PubMed

    Fleischer, Robert C; James, Helen F; Olson, Storrs L

    2008-12-23

    The Hawaiian "honeyeaters," five endemic species of recently extinct, nectar-feeding songbirds in the genera Moho and Chaetoptila, looked and acted like Australasian honeyeaters (Meliphagidae), and no taxonomist since their discovery on James Cook's third voyage has classified them as anything else. We obtained DNA sequences from museum specimens of Moho and Chaetoptila collected in Hawaii 115-158 years ago. Phylogenetic analysis of these sequences supports monophyly of the two Hawaiian genera but, surprisingly, reveals that neither taxon is a meliphagid honeyeater, nor even in the same part of the songbird radiation as meliphagids. Instead, the Hawaiian species are divergent members of a passeridan group that includes deceptively dissimilar families of songbirds (Holarctic waxwings, neotropical silky flycatchers, and palm chats). Here we designate them as a new family, the Mohoidae. A nuclear-DNA rate calibration suggests that mohoids diverged from their closest living ancestor 14-17 mya, coincident with the estimated earliest arrival in Hawaii of a bird-pollinated plant lineage. Convergent evolution, the evolution of similar traits in distantly related taxa because of common selective pressures, is illustrated well by nectar-feeding birds, but the morphological, behavioral, and ecological similarity of the mohoids to the Australasian honeyeaters makes them a particularly striking example of the phenomenon.

  3. Convergent evolution of Hawaiian and Australo-Pacific honeyeaters from distant songbird ancestors.

    PubMed

    Fleischer, Robert C; James, Helen F; Olson, Storrs L

    2008-12-23

    The Hawaiian "honeyeaters," five endemic species of recently extinct, nectar-feeding songbirds in the genera Moho and Chaetoptila, looked and acted like Australasian honeyeaters (Meliphagidae), and no taxonomist since their discovery on James Cook's third voyage has classified them as anything else. We obtained DNA sequences from museum specimens of Moho and Chaetoptila collected in Hawaii 115-158 years ago. Phylogenetic analysis of these sequences supports monophyly of the two Hawaiian genera but, surprisingly, reveals that neither taxon is a meliphagid honeyeater, nor even in the same part of the songbird radiation as meliphagids. Instead, the Hawaiian species are divergent members of a passeridan group that includes deceptively dissimilar families of songbirds (Holarctic waxwings, neotropical silky flycatchers, and palm chats). Here we designate them as a new family, the Mohoidae. A nuclear-DNA rate calibration suggests that mohoids diverged from their closest living ancestor 14-17 mya, coincident with the estimated earliest arrival in Hawaii of a bird-pollinated plant lineage. Convergent evolution, the evolution of similar traits in distantly related taxa because of common selective pressures, is illustrated well by nectar-feeding birds, but the morphological, behavioral, and ecological similarity of the mohoids to the Australasian honeyeaters makes them a particularly striking example of the phenomenon. PMID:19084408

  4. Mechanism of photoprotection in the cyanobacterial ancestor of plant antenna proteins.

    PubMed

    Staleva, Hristina; Komenda, Josef; Shukla, Mahendra K; Šlouf, Václav; Kaňa, Radek; Polívka, Tomáš; Sobotka, Roman

    2015-04-01

    Plants collect light for photosynthesis using light-harvesting complexes (LHCs)-an array of chlorophyll proteins that are able to reversibly switch from harvesting to energy-dissipation mode to prevent damage of the photosynthetic apparatus. LHC antennae as well as other members of the LHC superfamily evolved from cyanobacterial ancestors called high light-inducible proteins (Hlips). Here, we characterized a purified Hlip family member HliD isolated from the cyanobacterium Synechocystis sp. PCC 6803. We found that the HliD binds chlorophyll-a (Chl-a) and β-carotene and exhibits an energy-dissipative conformation. Using femtosecond spectroscopy, we demonstrated that the energy dissipation is achieved via direct energy transfer from a Chl-a Qy state to the β-carotene S1 state. We did not detect any cation of β-carotene that would accompany Chl-a quenching. These results provide proof of principle that this quenching mechanism operates in the LHC superfamily and also shed light on the photoprotective role of Hlips and the evolution of LHC antennae.

  5. Hybrid apomicts trapped in the ecological niches of their sexual ancestors.

    PubMed

    Mau, Martin; Lovell, John T; Corral, José M; Kiefer, Christiane; Koch, Marcus A; Aliyu, Olawale M; Sharbel, Timothy F

    2015-05-01

    Asexual reproduction is expected to reduce the adaptive potential to novel or changing environmental conditions, restricting or altering the ecological niche of asexual lineages. Asexual lineages of plants and animals are typically polyploid, an attribute that may influence their genetic variation, plasticity, adaptive potential, and niche breadth. The genus Boechera (Brassicaceae) represents an ideal model to test the relative ecological and biogeographic impacts of reproductive mode and ploidy because it is composed of diploid sexual and both diploid and polyploid asexual (i.e., apomictic) lineages. Here, we demonstrate a strong association between a transcriptionally conserved allele and apomictic seed formation. We then use this allele as a proxy apomixis marker in 1,649 accessions to demonstrate that apomixis is likely to be a common feature across the Boechera phylogeny. Phylogeographic analyses of these data demonstrate (i) species-specific niche differentiation in sexuals, (ii) extensive niche conservation between differing reproductive modes of the same species, (iii) ploidy-specific niche differentiation within and among species, and (iv) occasional niche drift between apomicts and their sexual ancestors. We conclude that ploidy is a substantially stronger and more common driver of niche divergence within and across Boechera species although variation in both traits may not necessarily lead to niche evolution on the species scale.

  6. CloudLCA: finding the lowest common ancestor in metagenome analysis using cloud computing.

    PubMed

    Zhao, Guoguang; Bu, Dechao; Liu, Changning; Li, Jing; Yang, Jian; Liu, Zhiyong; Zhao, Yi; Chen, Runsheng

    2012-02-01

    Estimating taxonomic content constitutes a key problem in metagenomic sequencing data analysis. However, extracting such content from high-throughput data of next-generation sequencing is very time-consuming with the currently available software. Here, we present CloudLCA, a parallel LCA algorithm that significantly improves the efficiency of determining taxonomic composition in metagenomic data analysis. Results show that CloudLCA (1) has a running time nearly linear with the increase of dataset magnitude, (2) displays linear speedup as the number of processors grows, especially for large datasets, and (3) reaches a speed of nearly 215 million reads each minute on a cluster with ten thin nodes. In comparison with MEGAN, a well-known metagenome analyzer, the speed of CloudLCA is up to 5 more times faster, and its peak memory usage is approximately 18.5% that of MEGAN, running on a fat node. CloudLCA can be run on one multiprocessor node or a cluster. It is expected to be part of MEGAN to accelerate analyzing reads, with the same output generated as MEGAN, which can be import into MEGAN in a direct way to finish the following analysis. Moreover, CloudLCA is a universal solution for finding the lowest common ancestor, and it can be applied in other fields requiring an LCA algorithm. PMID:22426983

  7. The evolution of air resonance power efficiency in the violin and its ancestors

    PubMed Central

    Nia, Hadi T.; Jain, Ankita D.; Liu, Yuming; Alam, Mohammad-Reza; Barnas, Roman; Makris, Nicholas C.

    2015-01-01

    The fact that acoustic radiation from a violin at air-cavity resonance is monopolar and can be determined by pure volume change is used to help explain related aspects of violin design evolution. By determining the acoustic conductance of arbitrarily shaped sound holes, it is found that air flow at the perimeter rather than the broader sound-hole area dominates acoustic conductance, and coupling between compressible air within the violin and its elastic structure lowers the Helmholtz resonance frequency from that found for a corresponding rigid instrument by roughly a semitone. As a result of the former, it is found that as sound-hole geometry of the violin's ancestors slowly evolved over centuries from simple circles to complex f-holes, the ratio of inefficient, acoustically inactive to total sound-hole area was decimated, roughly doubling air-resonance power efficiency. F-hole length then slowly increased by roughly 30% across two centuries in the renowned workshops of Amati, Stradivari and Guarneri, favouring instruments with higher air-resonance power, through a corresponding power increase of roughly 60%. By evolution-rate analysis, these changes are found to be consistent with mutations arising within the range of accidental replication fluctuations from craftsmanship limitations with subsequent selection favouring instruments with higher air-resonance power. PMID:25792964

  8. Hybrid apomicts trapped in the ecological niches of their sexual ancestors.

    PubMed

    Mau, Martin; Lovell, John T; Corral, José M; Kiefer, Christiane; Koch, Marcus A; Aliyu, Olawale M; Sharbel, Timothy F

    2015-05-01

    Asexual reproduction is expected to reduce the adaptive potential to novel or changing environmental conditions, restricting or altering the ecological niche of asexual lineages. Asexual lineages of plants and animals are typically polyploid, an attribute that may influence their genetic variation, plasticity, adaptive potential, and niche breadth. The genus Boechera (Brassicaceae) represents an ideal model to test the relative ecological and biogeographic impacts of reproductive mode and ploidy because it is composed of diploid sexual and both diploid and polyploid asexual (i.e., apomictic) lineages. Here, we demonstrate a strong association between a transcriptionally conserved allele and apomictic seed formation. We then use this allele as a proxy apomixis marker in 1,649 accessions to demonstrate that apomixis is likely to be a common feature across the Boechera phylogeny. Phylogeographic analyses of these data demonstrate (i) species-specific niche differentiation in sexuals, (ii) extensive niche conservation between differing reproductive modes of the same species, (iii) ploidy-specific niche differentiation within and among species, and (iv) occasional niche drift between apomicts and their sexual ancestors. We conclude that ploidy is a substantially stronger and more common driver of niche divergence within and across Boechera species although variation in both traits may not necessarily lead to niche evolution on the species scale. PMID:25902513

  9. Crops gone wild: evolution of weeds and invasives from domesticated ancestors

    PubMed Central

    Ellstrand, Norman C; Heredia, Sylvia M; Leak-Garcia, Janet A; Heraty, Joanne M; Burger, Jutta C; Yao, Li; Nohzadeh-Malakshah, Sahar; Ridley, Caroline E

    2010-01-01

    The evolution of problematic plants, both weeds and invasives, is a topic of increasing interest. Plants that have evolved from domesticated ancestors have certain advantages for study. Because of their economic importance, domesticated plants are generally well-characterized and readily available for ecogenetic comparison with their wild descendants. Thus, the evolutionary history of crop descendants has the potential to be reconstructed in some detail. Furthermore, growing crop progenitors with their problematic descendants in a common environment allows for the identification of significant evolutionary differences that correlate with weediness or invasiveness. We sought well-established examples of invasives and weeds for which genetic and/or ethnobotanical evidence has confirmed their evolution from domesticates. We found surprisingly few cases, only 13. We examine our list for generalizations and then some selected cases to reveal how plant pests have evolved from domesticates. Despite their potential utility, crop descendants remain underexploited for evolutionary study. Promising evolutionary research opportunities for these systems are abundant and worthy of pursuit. PMID:25567942

  10. Comparison of vitrified outcomes between human early blastocysts and expanded blastocysts.

    PubMed

    Song, Wen-Yan; Wang, Xue-Gai; Jin, Hai-Xia; Yao, Gui-Dong; Zhang, Xiang-Yang; Shi, Sen-Lin; Yang, Hong-Yi; Peng, Zhao-Feng; Sun, Ying-Pu

    2016-05-01

    We compared the vitrified outcomes between early and expanded blastocysts with or without laser drilling. The grade III embryos from the patients undergoing in vitro fertilization-embryo transfer (IVF-ET) in our reproductive center from September 2009 to February 2015 were incubated into early blastocysts and expanded blastocysts. The early blastocysts and expanded blastocysts were, respectively, divided into laser group (vitrification after laser drilling), non-laser group (direct vitrification), and control group (fresh non-vitrified blastocysts). After thawing, the blastular anabiosis rate, expansion rate, hatching rate, and apoptosis were observed in each group and then were compared amongst groups. This study indicated that the blastular expansion rate (all P < 0.01) and hatching rate (all P < 0.01) were significantly lower, but the blastular apoptosis (all P < 0.05) was significantly higher in both laser and non-laser groups than in the control group in the early blastocysts. In the expanded blastocysts, the blastular anabiosis rate was significantly higher in the laser group than in the non-laser group (P < 0.01), and the blastular expansion rate was significantly higher, but the blastular apoptosis was significantly lower in both laser group and control group than in the non-laser group (all P < 0.05). The blastular expansion rate (all P < 0.01) and hatching rate (all P < 0.01) were significantly higher, but the blastular apoptosis (all P < 0.05) was significantly lower in the expanded laser group than in both early laser and early non-laser groups. We conclude that vitrification for laser-drilling expanded blastocysts can achieve the best outcomes. PMID:26956359

  11. Early Trabecular Development in Human Vertebrae: Overproduction, Constructive Regression, and Refinement

    PubMed Central

    Acquaah, Frank; Robson Brown, Katharine A.; Ahmed, Farah; Jeffery, Nathan; Abel, Richard L.

    2015-01-01

    Early bone development may have a significant impact upon bone health in adulthood. Bone mineral density (BMD) and bone mass are important determinants of adult bone strength. However, several studies have shown that BMD and bone mass decrease after birth. If early development is important for strength, why does this reduction occur? To investigate this, more data characterizing gestational, infant, and childhood bone development are needed in order to compare with adults. The aim of this study is to document early vertebral trabecular bone development, a key fragility fracture site, and infer whether this period is important for adult bone mass and structure. A series of 120 vertebrae aged between 6 months gestation and 2.5 years were visualized using microcomputed tomography. Spherical volumes of interest were defined, thresholded, and measured using 3D bone analysis software (BoneJ, Quant3D). The findings showed that gestation was characterized by increasing bone volume fraction whilst infancy was defined by significant bone loss (≈2/3rds) and the appearance of a highly anisotropic trabecular structure with a predominantly inferior–superior direction. Childhood development progressed via selective thickening of some trabeculae and the loss of others; maintaining bone volume whilst creating a more anisotropic structure. Overall, the pattern of vertebral development is one of gestational overproduction followed by infant “sculpting” of bone tissue during the first year of life (perhaps in order to regulate mineral homeostasis or to adapt to loading environment) and then subsequent refinement during early childhood. Comparison of early bone developmental data in this study with adult bone volume values taken from the literature shows that the loss in bone mass that occurs during the first year of life is never fully recovered. Early development could therefore be important for developing bone strength, but through structural changes in trabecular

  12. Tempo and mode in human evolution.

    PubMed Central

    McHenry, H M

    1994-01-01

    The quickening pace of paleontological discovery is matched by rapid developments in geochronology. These new data show that the pattern of morphological change in the hominid lineage was mosaic. Adaptations essential to bipedalism appeared early, but some locomotor features changed much later. Relative to the highly derived postcrania of the earliest hominids, the craniodental complex was quite primitive (i.e., like the reconstructed last common ancestor with the African great apes). The pattern of craniodental change among successively younger species of Hominidae implies extensive parallel evolution between at least two lineages in features related to mastication. Relative brain size increased slightly among successively younger species of Australopithecus, expanded significantly with the appearance of Homo, but within early Homo remained at about half the size of Homo sapiens for almost a million years. Many apparent trends in human evolution may actually be due to the accumulation of relatively rapid shifts in successive species. PMID:8041697

  13. The importance of understanding the human-animal interface : from early hominins to global citizens.

    PubMed