Before the dawn recovering the lost history of our ancestors

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Wade, Nicholas

2007-01-01

Nicholas Wade’s articles are a major reason why the science section has become the most popular, nationwide, in the New York Times. In his groundbreaking Before the Dawn, Wade reveals humanity’s origins as never before—a journey made possible only recently by genetic science, whose incredible findings have answered such questions as: What was the first human language like? How large were the first societies, and how warlike were they? When did our ancestors first leave Africa, and by what route did they leave? By eloquently solving these and numerous other mysteries, Wade offers nothing less than a uniquely complete retelling of a story that began 500 centuries ago.

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

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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

The Five Ancestors--Book 1: Tiger

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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.

Mitochondrial lineage M1 traces an early human backflow to Africa.

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

2007-07-09

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. 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. 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.

Mitochondrial lineage M1 traces an early human backflow to Africa

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Pestano José

2007-07-01

Full Text Available Abstract 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.

Outgroup, alignment and modelling improvements indicate that two TNFSF13-like genes existed in the vertebrate ancestor.

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Redmond, Anthony K; Pettinello, Rita; Dooley, Helen

2017-03-01

The molecular machinery required for lymphocyte development and differentiation appears to have emerged concomitantly with distinct B- and T-like lymphocyte subsets in the ancestor of all vertebrates. The TNFSF superfamily (TNFSF) members BAFF (TNFSF13/Blys) and APRIL (TNFSF13) are key regulators of B cell development survival, and activation in mammals, but the temporal emergence of these molecules, and their precise relationship to the newly identified TNFSF gene BALM (BAFF and APRIL-like molecule), have not yet been elucidated. Here, to resolve the early evolutionary history of this family, we improved outgroup sampling and alignment quality, and applied better fitting substitution models compared to past studies. Our analyses reveal that BALM is a definitive TNFSF13 family member, which split from BAFF in the gnathostome (jawed vertebrate) ancestor. Most importantly, however, we show that both the APRIL and BAFF lineages existed in the ancestors of all extant vertebrates. This implies that APRIL has been lost, or is yet to be found, in cyclostomes (jawless vertebrates). Our results suggest that lineage-specific gene duplication and loss events have caused lymphocyte regulation, despite shared origins, to become secondarily distinct between gnathostomes and cyclostomes. Finally, the structure of lamprey BAFF-like, and its phylogenetic placement as sister to BAFF and BALM, but not the more slowly evolving APRIL, indicates that the primordial lymphocyte regulator was more APRIL-like than BAFF-like.

Information-Theoretic Inference of Common Ancestors

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Bastian Steudel

2015-04-01

Full Text Available A directed acyclic graph (DAG partially represents the conditional independence structure among observations of a system if the local Markov condition holds, that is if every variable is independent of its non-descendants given its parents. In general, there is a whole class of DAGs that represents a given set of conditional independence relations. We are interested in properties of this class that can be derived from observations of a subsystem only. To this end, we prove an information-theoretic inequality that allows for the inference of common ancestors of observed parts in any DAG representing some unknown larger system. More explicitly, we show that a large amount of dependence in terms of mutual information among the observations implies the existence of a common ancestor that distributes this information. Within the causal interpretation of DAGs, our result can be seen as a quantitative extension of Reichenbach’s principle of common cause to more than two variables. Our conclusions are valid also for non-probabilistic observations, such as binary strings, since we state the proof for an axiomatized notion of “mutual information” that includes the stochastic as well as the algorithmic version.

Apparatus Named after Our Academic Ancestors, III

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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.

Ancestors protocol for scalable key management

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Dieter Gollmann

2010-06-01

Full Text Available Group key management is an important functional building block for secure multicast architecture. Thereby, it has been extensively studied in the literature. The main proposed protocol is Adaptive Clustering for Scalable Group Key Management (ASGK. According to ASGK protocol, the multicast group is divided into clusters, where each cluster consists of areas of members. Each cluster uses its own Traffic Encryption Key (TEK. These clusters are updated periodically depending on the dynamism of the members during the secure session. The modified protocol has been proposed based on ASGK with some modifications to balance the number of affected members and the encryption/decryption overhead with any number of the areas when a member joins or leaves the group. This modified protocol is called Ancestors protocol. According to Ancestors protocol, every area receives the dynamism of the members from its parents. The main objective of the modified protocol is to reduce the number of affected members during the leaving and joining members, then 1 affects n overhead would be reduced. A comparative study has been done between ASGK protocol and the modified protocol. According to the comparative results, it found that the modified protocol is always outperforming the ASGK protocol.

Vacuum fluctuations in an ancestor vacuum: A possible dark energy candidate

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Aoki, Hajime; Iso, Satoshi; Lee, Da-Shin; Sekino, Yasuhiro; Yeh, Chen-Pin

2018-02-01

We consider an open universe created by bubble nucleation, and study possible effects of our "ancestor vacuum," a de Sitter space in which bubble nucleation occurred, on the present universe. We compute vacuum expectation values of the energy-momentum tensor for a minimally coupled scalar field, carefully taking into account the effect of the ancestor vacuum by the Euclidean prescription. We pay particular attention to the so-called supercurvature mode, a non-normalizable mode on a spatial slice of the open universe, which has been known to exist for sufficiently light fields. This mode decays in time most slowly, and may leave residual effects of the ancestor vacuum, potentially observable in the present universe. We point out that the vacuum energy of the quantum field can be regarded as dark energy if mass of the field is of order the present Hubble parameter or smaller. We obtain preliminary results for the dark energy equation of state w (z ) as a function of the redshift.

Environmental Adaptation from the Origin of Life to the Last Universal Common Ancestor

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Cantine, Marjorie D.; Fournier, Gregory P.

2018-03-01

Extensive fundamental molecular and biological evolution took place between the prebiotic origins of life and the state of the Last Universal Common Ancestor (LUCA). Considering the evolutionary innovations between these two endpoints from the perspective of environmental adaptation, we explore the hypothesis that LUCA was temporally, spatially, and environmentally distinct from life's earliest origins in an RNA world. Using this lens, we interpret several molecular biological features as indicating an environmental transition between a cold, radiation-shielded origin of life and a mesophilic, surface-dwelling LUCA. Cellularity provides motility and permits Darwinian evolution by connecting genetic material and its products, and thus establishing heredity and lineage. Considering the importance of compartmentalization and motility, we propose that the early emergence of cellularity is required for environmental dispersal and diversification during these transitions. Early diversification and the emergence of ecology before LUCA could be an important pre-adaptation for life's persistence on a changing planet.

The Ancestor Project: Aboriginal Computer Education through Storytelling

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Weston, Marla; Biin, Dianne

2013-01-01

The goal of the ANCESTOR program is to use digital storytelling as a means of promoting an interest in technology careers for Aboriginal learners, as well as increasing cultural literacy. A curriculum was developed and first tested with Aboriginal students at the LÁU,WELNEW Tribal School near Victoria, British Columbia, Canada. Based on feedback…

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

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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.

How old are chimpanzee communities? Time to the most recent common ancestor of the Y-chromosome in highly patrilocal societies.

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Langergraber, Kevin E; Rowney, Carolyn; Schubert, Grit; Crockford, Cathy; Hobaiter, Catherine; Wittig, Roman; Wrangham, Richard W; Zuberbühler, Klaus; Vigilant, Linda

2014-04-01

Many human societies are patrilineal, with males passing on their name or descent group affiliation to their offspring. Y-chromosomes are also passed on from father to son, leading to the simple expectation that males sharing the same surname or descent group membership should have similar Y-chromosome haplotypes. Although several studies in patrilineal human societies have examined the correspondence between Y-chromosome variation and surname or descent group membership, similar studies in non-human animals are lacking. Chimpanzees represent an excellent species for examining the relationship between descent group membership and Y-chromosome variation because they live in strongly male philopatric communities that arise by a group-fissioning process. Here we take advantage of recent analytical advances in the calculation of the time to the most recent common male ancestor and a large sample size of 273 Y-chromosome short tandem repeat haplotypes to inform our understanding of the potential ages of eight communities of chimpanzees. We find that the times to the most recent common male ancestor of chimpanzee communities are several hundred to as much as over two thousand years. These genetic estimates of the great time depths of chimpanzee communities accord well with behavioral observations suggesting that community fissions are a very rare event and are similar to genetic estimates of the time depth of patrilineal human groups. Copyright © 2014 Elsevier Ltd. All rights reserved.

Graves, Ancestors and Cement in Land disputes in Acholi and Ikland, Uganda

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Meinert, Lotte; Willerslev, Rane; Seebach, Sophie Hooge

2017-01-01

graves are made concrete and increasingly cemented indices of belonging in wrangles over land. Belonging is often justified through the presence of ancestor graves on land. The cementing of graves turns them into more concrete and durable proofs of ownership, and the reburial of relatives to disputed......The paper explores the roles of graves, ancestors and concrete pillars in disputes over land across different land-systems, -conflicts, and territory making in northern Uganda by comparing extended cases between Acholi in Gulu district and Ik in Kaabong district . In the post-conflict Acholi region...

The Common Ancestor of Archaea and Eukarya Was Not an Archaeon

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Patrick Forterre

2013-01-01

Full Text Available 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.

Extensive intron gain in the ancestor of placental mammals

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2011-01-01

Background Genome-wide studies of intron dynamics in mammalian orthologous genes have found convincing evidence for loss of introns but very little for intron turnover. Similarly, large-scale analysis of intron dynamics in a few vertebrate genomes has identified only intron losses and no gains, indicating that intron gain is an extremely rare event in vertebrate evolution. These studies suggest that the intron-rich genomes of vertebrates do not allow intron gain. The aim of this study was to search for evidence of de novo intron gain in domesticated genes from an analysis of their exon/intron structures. Results A phylogenomic approach has been used to analyse all domesticated genes in mammals and chordates that originated from the coding parts of transposable elements. Gain of introns in domesticated genes has been reconstructed on well established mammalian, vertebrate and chordate phylogenies, and examined as to where and when the gain events occurred. The locations, sizes and amounts of de novo introns gained in the domesticated genes during the evolution of mammals and chordates has been analyzed. A significant amount of intron gain was found only in domesticated genes of placental mammals, where more than 70 cases were identified. De novo gained introns show clear positional bias, since they are distributed mainly in 5' UTR and coding regions, while 3' UTR introns are very rare. In the coding regions of some domesticated genes up to 8 de novo gained introns have been found. Intron densities in Eutheria-specific domesticated genes and in older domesticated genes that originated early in vertebrates are lower than those for normal mammalian and vertebrate genes. Surprisingly, the majority of intron gains have occurred in the ancestor of placentals. Conclusions This study provides the first evidence for numerous intron gains in the ancestor of placental mammals and demonstrates that adequate taxon sampling is crucial for reconstructing intron evolution. The

Bilaterally symmetric axes with rhizoids composed the rooting structure of the common ancestor of vascular plants.

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Hetherington, Alexander J; Dolan, Liam

2018-02-05

There are two general types of rooting systems in extant land plants: gametophyte rhizoids and sporophyte root axes. These structures carry out the rooting function in the free-living stage of almost all land plant gametophytes and sporophytes, respectively. Extant vascular plants develop a dominant, free-living sporophyte on which roots form, with the exception of a small number of taxa that have secondarily lost roots. However, fossil evidence indicates that early vascular plants did not develop sporophyte roots. We propose that the common ancestor of vascular plants developed a unique rooting system-rhizoidal sporophyte axes. Here we present a synthesis and reinterpretation of the rootless sporophytes of Horneophyton lignieri , Aglaophyton majus , Rhynia gwynne-vaughanii and Nothia aphylla preserved in the Rhynie chert. We show that the sporophyte rooting structures of all four plants comprised regions of plagiotropic (horizontal) axes that developed unicellular rhizoids on their underside. These regions of axes with rhizoids developed bilateral symmetry making them distinct from the other regions which were radially symmetrical. We hypothesize that rhizoidal sporophyte axes constituted the rooting structures in the common ancestor of vascular plants because the phylogenetic positions of these plants span the origin of the vascular lineage.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'. © 2017 The Authors.

Algal ancestor of land plants was preadapted for symbiosis.

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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.

Fossils, feet and the evolution of human bipedal locomotion.

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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

The Waikato river: Changing properties of a living Māori ancestor

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Meijl, A.H.M. van

2015-01-01

In Māori cosmology, rivers and other waterways are conceptualised as living ancestors, who have their own life force and spiritual strength. The special status of rivers in Māori society also explains why they are sometimes separated from other Māori claims to natural resources of which they were

Working Memory: A Cognitive Limit to Non-Human Primate Recursive Thinking Prior to Hominid Evolution

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Dwight W. Read

2008-10-01

Full Text Available In this paper I explore the possibility that recursion is not part of the cognitive repertoire of non-human primates such as chimpanzees due to limited working memory capacity. Multiple lines of data, from nut cracking to the velocity and duration of cognitive development, imply that chimpanzees have a short-term memory size that limits working memory to dealing with two, or at most three, concepts at a time. If so, as a species they lack the cognitive capacity for recursive thinking to be integrated into systems of social organization and communication. If this limited working memory capacity is projected back to a common ancestor for Pan and Homo, it follows that early hominid ancestors would have had limited working memory capacity. Hence we should find evidence for expansion of working memory capacity during hominid evolution reflected in changes in the products of conceptually framed activities such as stone tool production. Data on the artifacts made by our hominid ancestors support this expansion hypothesis for hominid working memory, thereby leading to qualitative differences between Pan and Homo.

An Aboriginal Australian genome reveals separate human dispersals into Asia.

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Rasmussen, Morten; Guo, Xiaosen; Wang, Yong; Lohmueller, Kirk E; Rasmussen, Simon; Albrechtsen, Anders; Skotte, Line; Lindgreen, Stinus; Metspalu, Mait; Jombart, Thibaut; Kivisild, Toomas; Zhai, Weiwei; Eriksson, Anders; Manica, Andrea; Orlando, Ludovic; De La Vega, Francisco M; Tridico, Silvana; Metspalu, Ene; Nielsen, Kasper; Ávila-Arcos, María C; Moreno-Mayar, J Víctor; Muller, Craig; Dortch, Joe; Gilbert, M Thomas P; Lund, Ole; Wesolowska, Agata; Karmin, Monika; Weinert, Lucy A; Wang, Bo; Li, Jun; Tai, Shuaishuai; Xiao, Fei; Hanihara, Tsunehiko; van Driem, George; Jha, Aashish R; Ricaut, François-Xavier; de Knijff, Peter; Migliano, Andrea B; Gallego Romero, Irene; Kristiansen, Karsten; Lambert, David M; Brunak, Søren; Forster, Peter; Brinkmann, Bernd; Nehlich, Olaf; Bunce, Michael; Richards, Michael; Gupta, Ramneek; Bustamante, Carlos D; Krogh, Anders; Foley, Robert A; Lahr, Marta M; Balloux, Francois; Sicheritz-Pontén, Thomas; Villems, Richard; Nielsen, Rasmus; Wang, Jun; Willerslev, Eske

2011-10-07

We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no evidence of European admixture and estimate contamination levels to be below 0.5%. We show that Aboriginal Australians are descendants of an early human dispersal into eastern Asia, possibly 62,000 to 75,000 years ago. This dispersal is separate from the one that gave rise to modern Asians 25,000 to 38,000 years ago. We also find evidence of gene flow between populations of the two dispersal waves prior to the divergence of Native Americans from modern Asian ancestors. Our findings support the hypothesis that present-day Aboriginal Australians descend from the earliest humans to occupy Australia, likely representing one of the oldest continuous populations outside Africa.

Early development of the human pelvic diaphragm

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Koch, Wijnandus Franciscus Robertus Maria

2006-01-01

The last decade an increasing interest in the pelvic floor can be observed in medical sciences. The lack of data on the development of the human pelvic floor is striking. The early development of the human pelvic diaphragm was studied. Materials and methodsUse was made of 38 human embryos and

Correction to: A sophisticated, differentiated Golgi in the ancestor of eukaryotes.

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Barlow, Lael D; Nývltová, Eva; Aguilar, Maria; Tachezy, Jan; Dacks, Joel B

2018-03-28

Upon publication of the original article, Barlow et al. [1], the authors noticed that Fig. 4b contained an inaccuracy when additional data is taken into account. We inferred a loss of GRASP in the common ancestor of cryptophytes and archaeplastids, based on the absence of identified homologues in the data from taxa that we analyzed, which include Cyanidioschyzon merolae as the single representative of red algae.

The Out of Africa hypothesis and the ancestry of recent humans: Cherchez la femme (et l'homme).

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Árnason, Úlfur

2016-07-01

The Out of Africa hypothesis (OOAH) has been a mainstay in the discussion of human evolution since its presentation in the 1980's. However, recent advances in palaeontology and molecular genetics have made it possible to examine the hypothesis in a manner that was inconceivable at the time of its proposal. The palaeontological progress relates to early Homo finds in the Caucasus, Denisova finds in the Altai Mountains and Neanderthal finds in a wide range of localities from the Altai Mountains, the Caucasus, the Levant, Asia Minor, southern and Central Europe and the Iberian Peninsula. The Eurasian location of these finds and recognition of the principle of Last common ancestor (LCA) lend no support to OOAH. The same conclusion is drawn from genomic findings, which (a) have revealed the presence of Denisovan and Neanderthal nuclear DNA, primarily in the genomes of recent Eurasians and (b) have shown genomic introgression from early modern humans into Neanderthals in the Altai Mountains. Similarly, archaeological finds in Sulawesi and the discovery of ≈100,000years old human teeth in southern China constitute strong independent challenges to OOAH. The genomic and palaeogenomic results and the new palaeontological and archaeological discoveries suggest (a) that the ancestors of modern humans had their origin in a Eurasian (largely Asian) biogeographic region which may also have extended into NE Africa, and (b) that the founders of basal African lineages became separated, geographically and genetically, in the westernmost part of this region and spread from there to different parts of the African continent. Copyright © 2016 Elsevier B.V. All rights reserved.

The backbone of the post-synaptic density originated in a unicellular ancestor of choanoflagellates and metazoans

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Manuel Michaël

2010-02-01

Full Text Available Abstract Background Comparative genomics of the early diverging metazoan lineages and of their unicellular sister-groups opens new window to reconstructing the genetic changes which preceded or accompanied the evolution of multicellular body plans. A recent analysis found that the genome of the nerve-less sponges encodes the homologues of most vertebrate post-synaptic proteins. In vertebrate excitatory synapses, these proteins assemble to form the post-synaptic density, a complex molecular platform linking membrane receptors, components of their signalling pathways, and the cytoskeleton. Newly available genomes from Monosiga brevicollis (a member of Choanoflagellata, the closest unicellular relatives of animals and Trichoplax adhaerens (a member of Placozoa: besides sponges, the only nerve-less metazoans offer an opportunity to refine our understanding of post-synaptic protein evolution. Results Searches for orthologous proteins and reconstruction of gene gains/losses based on the taxon phylogeny indicate that post-synaptic proteins originated in two main steps. The backbone scaffold proteins (Shank, Homer, DLG and some of their partners were acquired in a unicellular ancestor of choanoflagellates and metazoans. A substantial additional set appeared in an exclusive ancestor of the Metazoa. The placozoan genome contains most post-synaptic genes but lacks some of them. Notably, the master-scaffold protein Shank might have been lost secondarily in the placozoan lineage. Conclusions The time of origination of most post-synaptic proteins was not concomitant with the acquisition of synapses or neural-like cells. The backbone of the scaffold emerged in a unicellular context and was probably not involved in cell-cell communication. Based on the reconstructed protein composition and potential interactions, its ancestral function could have been to link calcium signalling and cytoskeleton regulation. The complex later became integrated into the evolving

Heterokont predator Develorapax marinus gen. et sp. nov. – a model of the ochrophyte ancestor

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Vladimir V. Aleoshin

2016-08-01

Full Text Available 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 heteretrophic 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, and has likely occured in the ochrophyte ancestor.

‘Do larger molars and robust jaws in early hominins represent dietary adaptation?’ A New Study in Tooth Wear

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Anna Frances Clement

2013-10-01

Full Text Available Diet imposes significant constraints on the biology and behaviour of animals. The fossil record suggests that key changes in diet have taken place throughout the course of human evolution. Defining these changes enables us to understand the behaviour of our extinct fossil ancestors. Several lines of evidence are available for studying the diet of early hominins, including craniodental morphology, palaeoecology, dental microwear and stable isotopes. They do, however, often provide conflicting results. Using dental macrowear analysis, this new UCL Institute of Archaeology project will provide an alternative source of information on early hominin diet. Dental macrowear has often been used to analyse diet in archaeological populations, but this will be the first time that this type of detailed study has been applied to the early hominin fossil record.

Population Dynamics of Early Human Migration in Britain.

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Mayank N Vahia

Full Text Available 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.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.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.

Death and resurrection of the human IRGM gene.

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Cemalettin Bekpen

2009-03-01

Full Text Available Immunity-related GTPases (IRG play an important role in defense against intracellular pathogens. One member of this gene family in humans, IRGM, has been recently implicated as a risk factor for Crohn's disease. We analyzed the detailed structure of this gene family among primates and showed that most of the IRG gene cluster was deleted early in primate evolution, after the divergence of the anthropoids from prosimians ( about 50 million years ago. Comparative sequence analysis of New World and Old World monkey species shows that the single-copy IRGM gene became pseudogenized as a result of an Alu retrotransposition event in the anthropoid common ancestor that disrupted the open reading frame (ORF. We find that the ORF was reestablished as a part of a polymorphic stop codon in the common ancestor of humans and great apes. Expression analysis suggests that this change occurred in conjunction with the insertion of an endogenous retrovirus, which altered the transcription initiation, splicing, and expression profile of IRGM. These data argue that the gene became pseudogenized and was then resurrected through a series of complex structural events and suggest remarkable functional plasticity where alleles experience diverse evolutionary pressures over time. Such dynamism in structure and evolution may be critical for a gene family locked in an arms race with an ever-changing repertoire of intracellular parasites.

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

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Favre, Maroussia; Sornette, Didier

2012-10-07

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

Inventing Homo gardarensis: prestige, pressure, and human evolution in interwar Scandinavia.

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Kjaergaard, Peter C

2014-06-01

In the 1920s there were still very few fossil human remains to support an evolutionary explanation of human origins. Nonetheless, evolution as an explanatory framework was widely accepted. This led to a search for ancestors in several continents with fierce international competition. With so little fossil evidence available and the idea of a Missing Link as a crucial piece of evidence in human evolution still intact, many actors participated in the scientific race to identify the human ancestor. The curious case of Homo gardarensis serves as an example of how personal ambitions and national pride were deeply interconnected as scientific concerns were sometimes slighted in interwar palaeoanthropology.

Comparative symbiotic plasmid analysis indicates that symbiosis gene ancestor type affects plasmid genetic evolution.

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Wang, X; Zhao, L; Zhang, L; Wu, Y; Chou, M; Wei, G

2018-07-01

Rhizobial symbiotic plasmids play vital roles in mutualistic symbiosis with legume plants by executing the functions of nodulation and nitrogen fixation. To explore the gene composition and genetic constitution of rhizobial symbiotic plasmids, comparison analyses of 24 rhizobial symbiotic plasmids derived from four rhizobial genera was carried out. Results illustrated that rhizobial symbiotic plasmids had higher proportion of functional genes participating in amino acid transport and metabolism, replication; recombination and repair; carbohydrate transport and metabolism; energy production and conversion and transcription. Mesorhizobium amorphae CCNWGS0123 symbiotic plasmid - pM0123d had similar gene composition with pR899b and pSNGR234a. All symbiotic plasmids shared 13 orthologous genes, including five nod and eight nif/fix genes which participate in the rhizobia-legume symbiosis process. These plasmids contained nod genes from four ancestors and fix genes from six ancestors. The ancestral type of pM0123d nod genes was similar with that of Rhizobium etli plasmids, while the ancestral type of pM0123d fix genes was same as that of pM7653Rb. The phylogenetic trees constructed based on nodCIJ and fixABC displayed different topological structures mainly due to nodCIJ and fixABC ancestral type discordance. The study presents valuable insights into mosaic structures and the evolution of rhizobial symbiotic plasmids. This study compared 24 rhizobial symbiotic plasmids that included four genera and 11 species, illuminating the functional gene composition and symbiosis gene ancestor types of symbiotic plasmids from higher taxonomy. It provides valuable insights into mosaic structures and the evolution of symbiotic plasmids. © 2018 The Society for Applied Microbiology.

In pursuit of our ancestors' hand laterality.

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Bargalló, Amèlia; Mosquera, Marina; Lozano, Sergi

2017-10-01

The aim of this paper is to apply a previously published method (Bargalló and Mosquera, 2014) to the archaeological record, allowing us to identify the hand laterality of our ancestors and determine when and how this feature, which is exhibited most strongly in humans, appeared in our evolutionary history. The method focuses on identifying handedness by looking at the technical features of the flakes produced by a single knapper, and discovering how many flakes are required to ascertain their hand preference. This method can potentially be applied to the majority of archaeological sites, since flakes are the most abundant stone tools, and stone tools are the most widespread and widely-preserved remains from prehistory. For our study, we selected two Spanish sites: Gran Dolina-TD10.1 (Atapuerca) and Abric Romaní (Barcelona), which were occupied by pre-Neanderthal and Neanderthal populations, respectively. Our analyses indicate that a minimum number of eight flakes produced by the same knapper is required to ascertain their hand preference. Even though this figure is relatively low, it is quite difficult to obtain from many archaeological sites. In addition, there is no single technical feature that provides information about handedness, instead there is a combination of eight technical features, localised on the striking platforms and ventral surfaces. The raw material is not relevant where good quality rocks are used, in this case quartzite and flint, since most of them retain the technical features required for the analysis. Expertise is not an issue either, since the technical features analysed here only correlate with handedness (Bargalló and Mosquera, 2014). Our results allow us to tentatively identify one right-handed knapper among the pre-Neanderthals of level TD10.1 at Gran Dolina (Atapuerca), while four of the five Neanderthals analysed from Abric Romaní were right-handed. The hand preference of the fifth knapper from that location (AR5) remains unclear

The artiodactyl APOBEC3 innate immune repertoire shows evidence for a multi-functional domain organization that existed in the ancestor of placental mammals

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Andrésdóttir Valgerdur

2008-11-01

Full Text Available Abstract Background APOBEC3 (A3 proteins deaminate DNA cytosines and block the replication of retroviruses and retrotransposons. Each A3 gene encodes a protein with one or two conserved zinc-coordinating motifs (Z1, Z2 or Z3. The presence of one A3 gene in mice (Z2–Z3 and seven in humans, A3A-H (Z1a, Z2a-Z1b, Z2b, Z2c-Z2d, Z2e-Z2f, Z2g-Z1c, Z3, suggests extraordinary evolutionary flexibility. To gain insights into the mechanism and timing of A3 gene expansion and into the functional modularity of these genes, we analyzed the genomic sequences, expressed cDNAs and activities of the full A3 repertoire of three artiodactyl lineages: sheep, cattle and pigs. Results Sheep and cattle have three A3 genes, A3Z1, A3Z2 and A3Z3, whereas pigs only have two, A3Z2 and A3Z3. A comparison between domestic and wild pigs indicated that A3Z1 was deleted in the pig lineage. In all three species, read-through transcription and alternative splicing also produced a catalytically active double domain A3Z2-Z3 protein that had a distinct cytoplasmic localization. Thus, the three A3 genes of sheep and cattle encode four conserved and active proteins. These data, together with phylogenetic analyses, indicated that a similar, functionally modular A3 repertoire existed in the common ancestor of artiodactyls and primates (i.e., the ancestor of placental mammals. This mammalian ancestor therefore possessed the minimal A3 gene set, Z1-Z2-Z3, required to evolve through a remarkable series of eight recombination events into the present day eleven Z domain human repertoire. Conclusion The dynamic recombination-filled history of the mammalian A3 genes is consistent with the modular nature of the locus and a model in which most of these events (especially the expansions were selected by ancient pathogenic retrovirus infections.

Tempo and mode in human evolution.

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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

No evidence of Neandertal mtDNA contribution to early modern humans.

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David Serre

2004-03-01

Full Text Available 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.

An Aboriginal Australian Genome Reveals Separate Human Dispersals into Asia

DEFF Research Database (Denmark)

Rasmussen, Morten; Guo, Xiaosen; Wang, Yong

2011-01-01

We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no evidence of European admixture and estimate contamination levels to be below 0.5%. We show that Abori......We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no evidence of European admixture and estimate contamination levels to be below 0.5%. We show...... that Aboriginal Australians are descendants of an early human dispersal into eastern Asia, possibly 62,000 to 75,000 years ago. This dispersal is separate from the one that gave rise to modern Asians 25,000 to 38,000 years ago. We also find evidence of gene flow between populations of the two dispersal waves...... prior to the divergence of Native Americans from modern Asian ancestors. Our findings support the hypothesis that present-day Aboriginal Australians descend from the earliest humans to occupy Australia, likely representing one of the oldest continuous populations outside Africa....

Hunter-Gatherers and the Origins of Religion.

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Peoples, Hervey C; Duda, Pavel; Marlowe, Frank W

2016-09-01

Recent studies of the evolution of religion have revealed the cognitive underpinnings of belief in supernatural agents, the role of ritual in promoting cooperation, and the contribution of morally punishing high gods to the growth and stabilization of human society. The universality of religion across human society points to a deep evolutionary past. However, specific traits of nascent religiosity, and the sequence in which they emerged, have remained unknown. Here we reconstruct the evolution of religious beliefs and behaviors in early modern humans using a global sample of hunter-gatherers and seven traits describing hunter-gatherer religiosity: animism, belief in an afterlife, shamanism, ancestor worship, high gods, and worship of ancestors or high gods who are active in human affairs. We reconstruct ancestral character states using a time-calibrated supertree based on published phylogenetic trees and linguistic classification and then test for correlated evolution between the characters and for the direction of cultural change. Results indicate that the oldest trait of religion, present in the most recent common ancestor of present-day hunter-gatherers, was animism, in agreement with long-standing beliefs about the fundamental role of this trait. Belief in an afterlife emerged, followed by shamanism and ancestor worship. Ancestor spirits or high gods who are active in human affairs were absent in early humans, suggesting a deep history for the egalitarian nature of hunter-gatherer societies. There is a significant positive relationship between most characters investigated, but the trait "high gods" stands apart, suggesting that belief in a single creator deity can emerge in a society regardless of other aspects of its religion.

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

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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. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Reconstructing the early evolution of the fungi using a six gene phylogeny

NARCIS (Netherlands)

James, T.Y.; Kauff, F.; Schoch, C.L.; Matheny, P.B.; Hofstetter, V.; Cox, C.J.; Celio, G.; Gueidan, C.; Fraker, E.; Miadlikowska, J.; Lumbsch, H.T.; Rauhut, A.; Reeb, V.; Arnold, A.E.; Amtoft, A.; Stajich, J.E.; Hosaka, K.; Sung, G.H.; Johnson, D.; O'Rourke, B.; Binder, M.; Curtis, J.M.; Slot, J.C.; Wang, Z.; Wilson, A.W.; Schüßler, A.; Longcore, J.E.; O'Donnell, K.; Mozley-Standridge, S.; Porter, D.; Letcher, P.M.; Powell, M.J.; Taylor, J.W.; White, M.M.; Griffith, G.W.; Davies, D.R.; Sugiyama, J.; Rossman, A.Y.; Rogers, J.D.; Pfister, D.H.; Hewitt, D.; Hansen, K.; Hambleton, S.; Shoemaker, R.A.; Kohlmeyer, J.; Volkmann-Kohlmeyer, B.; Spotts, R.A.; Serdani, M.; Crous, P.W.; Hughes, K.W.; Matsuura, K.; Langer, E.; Langer, G.; Untereiner, W.A.; Lücking, R.; Büdel, B.; Geiser, D.M.; Aptroot, A.; Diederich, P.; Schmitt, I.; Schultz, M.; Yahr, R.; Hibbett, D.S.; Lutzoni, F.; McLaughlin, D.J.; Spatafora, J.W.; Vilgalys, R.

2006-01-01

The ancestors of fungi are believed to be simple aquatic forms with flagellated spores, similar to members of the extant phylum Chytridiomycota (chytrids). Current classifications assume that chytrids form an early-diverging clade within the kingdom Fungi and imply a single loss of the spore

The human and fire connection

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Theresa B. Jain

2014-01-01

We refer to fire as a natural disturbance, but unlike other disturbances such as forest insects and diseases, fire has had an intimate relationship with humans. Fire facilitated human evolution over two million years ago when our ancestors began to use fire to cook. Fire empowered our furbearers to adapt to cold climates, allowing humans to disperse and settle into...

The environmental context of human evolutionary history in Eurasia and Africa.

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Elton, Sarah

2008-04-01

This review has three main aims: (1) to make specific predictions about the habitat of the hypothetical last common ancestor of the chimpanzee/bonobo-human clade; (2) to outline the major trends in environments between 8-6 Ma and the late Pleistocene; and (3) to pinpoint when, and in some cases where, human ancestors evolved to cope with the wide range of habitats they presently tolerate. Several lines of evidence indicate that arboreal environments, particularly woodlands, were important habitats for late Miocene hominids and hominins, and therefore possibly for the last common ancestor of the chimpanzee/bonobo-human clade. However, as there is no clear candidate for this last common ancestor, and because the sampling of fossils and past environments is inevitably patchy, this prediction remains a working hypothesis at best. Nonetheless, as a primate, it is expected that the last common ancestor was ecologically dependent on trees in some form. Understanding past environments is important, as palaeoenvironmental reconstructions provide the context for human morphological and behavioural evolution. Indeed, the impact of climate on the evolutionary history of our species has long been debated. Since the mid-Miocene, the Earth has been experiencing a general cooling trend accompanied by aridification, which intensified during the later Pliocene and Pleistocene. Numerous climatic fluctuations, as well as local, regional and continental geography that influenced weather patterns and vegetation, created hominin environments that were dynamic in space and time. Behavioural flexibility and cultural complexity were crucial aspects of hominin expansion into diverse environments during the Pleistocene, but the ability to exploit varied and varying habitats was established much earlier in human evolutionary history. The development of increasingly complex tool technology facilitated re-expansion into tropical forests. These environments are difficult for obligate bipeds to

Models of gene gain and gene loss for probabilistic reconstruction of gene content in the last universal common ancestor of life

OpenAIRE

Kannan, Lavanya; Li, Hua; Rubinstein, Boris; Mushegian, Arcady

2013-01-01

Background The problem of probabilistic inference of gene content in the last common ancestor of several extant species with completely sequenced genomes is: for each gene that is conserved in all or some of the genomes, assign the probability that its ancestral gene was present in the genome of their last common ancestor. Results We have developed a family of models of gene gain and gene loss in evolution, and applied the maximum-likelihood approach that uses phylogenetic tree of prokaryotes...

Hormone patterns in early human gestation

International Nuclear Information System (INIS)

Mishell, D.R. Jr.; Thorneycroft, I.H.; Nagata, Y.; Murata, T.; Nakamura, R.M.

1974-01-01

Accurate measurement of the low concentration of gonadotropins and steroid hormones present in human serum has been made possible by the development of sensitive radioimmunoassay (RIA) techniques. With the use of RIA FSH and LH, progesterone and 17OH-progesterone have been previously measured in early normal pregnancy. In order to determine the daily pattern of hormone levels in early normal pregnancy, gonadotropins as well as steroid hormone levels were measured in serum samples obtained daily from three women from the time of the last menstrual period prior to conception throughout the first few months of gestation. To further identify the steroid hormone pattern in early normal pregnancy, concentrations of estradiol, progesterone, and 17OH-progesterone were measured in individual serum samples obtained from a group of 158 women with apparently normal gestations who subsequently had therapeutic abortions. (auth)

The impact of 'anthropotechnology’ on human evolution

NARCIS (Netherlands)

Blad, S.

2010-01-01

From the time that they diverged from their common ancestor, chimpanzees and humans have had a very different evolutionary path. It seems obvious that the appearance of culture and technology has increasingly alienated humans from the path of natural selection that has informed chimpanzee evolution.

“Ancestors We Didn’t Even Know We Had”: Alice Walker, Asian Religion, and Ethnic Authenticity

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Kyle Garton-Gundling

2015-03-01

Full Text Available Recent debates about the ethics of identity in a global age have dealt with how to prioritize conflicting local and global allegiances. Guided by these concerns, the fiction of Alice Walker develops a distinctive view of how local cultures and global movements can fruitfully interact. This vision depends on concepts from Asian religions, a major influence that critics of Walker have largely overlooked. Walker promotes Hindu and Buddhist meditation in a context of widespread African American skepticism toward Asian religions. According to widespread notions of cultural authenticity, Asian religions cannot nourish an African American connection to ethnic roots. In response to this challenge, Alice Walker’s fiction portrays Hindu and Buddhist mystics as African Americans’ ancestors, thus positioning these faiths as authentically black. By creatively enfolding Asian religions into her sense of African American heritage, Walker builds a spiritual cosmopolitanism that relies on claims of ancestral affiliation even when these claims are not literal. This strategy is Walker’s effort to create a new paradigm of cultural authenticity, one that allows individuals and groups to choose their ancestors. Walker’s approach seeks to incorporate disparate global influences while still valorizing the figure of the ancestor. This innovative approach places Walker at the forefront of a growing number of African American artists and intellectuals who promote Asian religions to American minorities. Walker’s work vividly dramatizes larger concerns in transnational American Studies: Eastern philosophy’s relevance to identity politics, the tensions between universal ideals and cultural specifics, and the ethics of cross-cultural appropriation.

Environment and Climate of Early Human Evolution

Science.gov (United States)

Levin, Naomi E.

2015-05-01

Evaluating the relationships between climate, the environment, and human traits is a key part of human origins research because changes in Earth's atmosphere, oceans, landscapes, and ecosystems over the past 10 Myr shaped the selection pressures experienced by early humans. In Africa, these relationships have been influenced by a combination of high-latitude ice distributions, sea surface temperatures, and low-latitude orbital forcing that resulted in large oscillations in vegetation and moisture availability that were modulated by local basin dynamics. The importance of both climate and tectonics in shaping African landscapes means that integrated views of the ecological, environmental, and tectonic histories of a region are necessary in order to understand the relationships between climate and human evolution.

Sympathetic activation during early pregnancy in humans

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Jarvis, Sara S; Shibata, Shigeki; Bivens, Tiffany B; Okada, Yoshiyuki; Casey, Brian M; Levine, Benjamin D; Fu, Qi

2012-01-01

Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min−1, 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min−1; main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm−5; P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.−1 min−1; P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml−1, P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml−1, P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications. PMID:22687610

Origins and early development of human body knowledge.

Science.gov (United States)

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

Micro-dosing for early biokinetic studies in humans

International Nuclear Information System (INIS)

Stenstroem, K.; Sydoff, M.; Mattsson, S.

2010-01-01

Micro-dosing is a new concept in drug development that-if implemented in the pharmaceutical industry-would mean that new drugs can be tested earlier in humans than done today. The human micro-dosing concept-or 'Phase 0'-may offer improved candidate selection, reduced failure rates in the drug development line and a reduction in the use of laboratory animals in early drug development, factors which will help to speed up drug development and also reduce the costs. Micro-dosing utilises sub-pharmacological amounts of the substance to open opportunities for early studies in man. Three technologies are used for micro-dosing: accelerator mass spectrometry (AMS), positron emission tomography and liquid chromatography-tandem mass spectrometry. This paper focuses on the principle of AMS and discusses the current status of micro-dosing with AMS. (authors)

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

Science.gov (United States)

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.

["The first stages of the human egg" by Auguste d'Eternod published one hundred years ago in the Comptes Rendus de l'Association des Anatomistes].

Science.gov (United States)

Catala, M

2014-06-01

The development of the embryo and foetus fascinates, but its study in humans is difficult because of both technical and ethical problems. Auguste d'Eternod, Swiss embryologist, published in 1913 an article entitled "The early stages of the human egg" in the Comptes Rendus de l'Association des Anatomistes, the ancestor of the journal Morphologie. This work is focused not only on the early stages of development: fertilization, cleavage of the egg, blastocyst formation, gastrulation, but also on the extra-embryonic processes characteristic of mammals. On the occasion of the centenary of the publication of this work, I propose a critical review by placing the data published in the literature and historical context of the time. Finally, I try to extract from these observations the concepts that are still used today by embryologists. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

International Nuclear Information System (INIS)

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

1987-01-01

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

Human genetics: measuring the raw material of evolution.

Science.gov (United States)

Armour, John A L

2009-09-15

By direct sequencing of two Y chromosomes inherited from the same paternal ancestor, a landmark study has derived a good direct estimate for the rate of base substitution mutations on the human Y chromosome.

Dendritic Cell Lineage Potential in Human Early Hematopoietic Progenitors

Directory of Open Access Journals (Sweden)

Julie Helft

2017-07-01

Full Text Available Conventional dendritic cells (cDCs are thought to descend from a DC precursor downstream of the common myeloid progenitor (CMP. However, a mouse lymphoid-primed multipotent progenitor has been shown to generate cDCs following a DC-specific developmental pathway independent of monocyte and granulocyte poiesis. Similarly, here we show that, in humans, a large fraction of multipotent lymphoid early progenitors (MLPs gives rise to cDCs, in particular the subset known as cDC1, identified by co-expression of DNGR-1 (CLEC9A and CD141 (BDCA-3. Single-cell analysis indicates that over one-third of MLPs have the potential to efficiently generate cDCs. cDC1s generated from CMPs or MLPs do not exhibit differences in transcriptome or phenotype. These results demonstrate an early imprinting of the cDC lineage in human hematopoiesis and highlight the plasticity of developmental pathways giving rise to human DCs.

Microstructural Changes of the Human Brain from Early to Mid-Adulthood

OpenAIRE

Tian, Lixia; Ma, Lin

2017-01-01

Despite numerous studies on the microstructural changes of the human brain throughout life, we have indeed little direct knowledge about the changes from early to mid-adulthood. The aim of this study was to investigate the microstructural changes of the human brain from early to mid-adulthood. We performed two sets of analyses based on the diffusion tensor imaging (DTI) data of 111 adults aged 18–55 years. Specifically, we first correlated age with skeletonized fractional anisotropy (FA), mea...

Variability in an early hominin percussive tradition: the Acheulean versus cultural variation in modern chimpanzee artefacts.

Science.gov (United States)

Gowlett, J A J

2015-11-19

Percussion makes a vital link between the activities of early human ancestors and other animals in tool-use and tool-making. Far more of the early human actions are preserved as archaeology, since the percussion was largely used for making hard tools of stone, rather than for direct access to food. Both primate tools and early hominin tools, however, offer a means to exploring variability in material culture, a strong focus of interest in recent primate studies. This paper charts such variability in the Acheulean, the longest-lasting tool tradition, extant form about 1.7 to about 0.1 Ma, and well known for its characteristic handaxes. The paper concentrates on the African record, although the Acheulean was also known in Europe and Asia. It uses principal components and discriminant analysis to examine the measurements from 66 assemblages (whole toolkits), and from 18 sets of handaxes. Its review of evidence confirms that there is deep-seated pattern in the variation, with variability within a site complex often matching or exceeding that between sites far distant in space and time. Current techniques of study allow comparisons of handaxes far more easily than for other components, stressing a need to develop common practice in measurement and analysis. The data suggest, however, that a higher proportion of traits recurs widely in Acheulean toolkits than in the chimpanzee record. © 2015 The Author(s).

FINE SPECIFICITY OF CELLULAR IMMUNE-RESPONSES IN HUMANS TO HUMAN CYTOMEGALOVIRUS IMMEDIATE-EARLY 1-PROTEIN

NARCIS (Netherlands)

ALP, NJ; ALLPORT, TD; VANZANTEN, J; RODGERS, B; SISSONS, JGP; BORYSIEWICZ, LK

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

Direct dating of Early Upper Palaeolithic human remains from Mladec.

Science.gov (United States)

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

2005-05-19

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

Involvement of human endogenous retroviral syncytin-1 in human osteoclast fusion

DEFF Research Database (Denmark)

Søe, Kent; Andersen, Thomas Lykke; Hobolt-Pedersen, Anne-Sofie

2011-01-01

fusion of the lipid bilayers of their cell membranes are still unknown. Syncytin-1 is a protein encoded by a human endogenous retroviral gene which was stably integrated into the human ancestor genome more than 24 million years ago. Upon activation, syncytin-1 is able to destabilize the lipid bilayer....... This was documented through Q-PCR, Western blot and immunofluorescence analyses. These in vitro findings were confirmed by immunohistochemical stainings in human iliac crest biopsies. A syncytin-1 inhibitory peptide reduced the number of nuclei per osteoclast by 30%, as well as TRACP activity. From a mechanistic...

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

Science.gov (United States)

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…

Inventing Homo gardarensis: Prestige, Pressure and Human Evolution in Interwar Scandinavia

DEFF Research Database (Denmark)

Kjærgaard, Peter C.

2014-01-01

In the 1920s there were still very few fossil human remains to support an evolutionary explanation of human origins. Nonetheless, evolution as an explanatory framework was widely accepted. This led to a search for ancestors in several continents with fierce international competition. With so litt...

The Human Microbiota in Early Life

DEFF Research Database (Denmark)

Mortensen, Martin Steen

The bacteria that colonize the human body, our microbiota, can influence our health, both positively and negatively. The importance and functions of the microbiota in our intestinal tract have been the focus of several research projects and are widely published. However, there are great gaps in our...... knowledge concerning microbiota composition, development and function in other areas of human body. Lack of knowledge about the microbiota development in the airways is an example of such a deficiency. The work presented in this PhD thesis is based on the vast sample collection of the COPSAC2010 cohort......, with 700 mother-infant pairs. The objectives were to perform a detailed examination of the mothers’ vaginal microbiota, describe the early composition and development of the microbiota in the airways of their infants, and determine whether the infants’ microbiota are affected by that of their mothers...

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

Science.gov (United States)

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.

A proposal of the proteome before the last universal common ancestor (LUCA)

Science.gov (United States)

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.

PARTIAL REPRODUCTIVE ISOLATION OF A RECENTLY DERIVED RESIDENT-FRESHWATER POPULATION OF THREESPINE STICKLEBACK (GASTEROSTEUS ACULEATUS) FROM ITS PUTATIVE ANADROMOUS ANCESTOR

Science.gov (United States)

Furin, Christoff G.; Von Hippel, Frank A.; Bell, Michael A.

2012-01-01

We used no-choice mating trials to test for assortative mating between a newly derived resident-freshwater population (8 – 22 generations since founding) of threespine stickleback (Gasterosteus aculeatus) in Loberg Lake, Alaska and its putative anadromous ancestor as well as a morphologically convergent but distantly related resident-freshwater population. Partial reproductive isolation has evolved between the Loberg Lake population and its ancestor within a remarkably short time period. However, Loberg stickleback readily mate with morphologically similar, but distantly related resident-freshwater stickleback. Partial pre-mating isolation is asymmetrical; anadromous females and smaller, resident-freshwater males from Loberg Lake readily mate, but the anadromous males and smaller Loberg females do not. Our results indicate that pre-mating isolation can begin to evolve in allopatry within a few generations after isolation as a correlated effect of evolution of reduced body size. PMID:23025615

"Unwilling" versus "Unable": Capuchin Monkeys' ("Cebus Apella") Understanding of Human Intentional Action

Science.gov (United States)

Phillips, Webb; Barnes, Jennifer L.; Mahajan, Neha; Yamaguchi, Mariko; Santos, Laurie R.

2009-01-01

A sensitivity to the intentions behind human action is a crucial developmental achievement in infants. Is this intention reading ability a unique and relatively recent product of human evolution and culture, or does this capacity instead have roots in our non-human primate ancestors? Recent work by Call and colleagues (2004) lends credence to the…

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

Science.gov (United States)

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

Early development of synchrony in cortical activations in the human.

Science.gov (United States)

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

2016-05-13

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. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Function of FEZF1 during early neural differentiation of human embryonic stem cells.

Science.gov (United States)

Liu, Xin; Su, Pei; Lu, Lisha; Feng, Zicen; Wang, Hongtao; Zhou, Jiaxi

2018-01-01

The understanding of the mechanism underlying human neural development has been hampered due to lack of a cellular system and complicated ethical issues. Human embryonic stem cells (hESCs) provide an invaluable model for dissecting human development because of unlimited self-renewal and the capacity to differentiate into nearly all cell types in the human body. In this study, using a chemical defined neural induction protocol and molecular profiling, we identified Fez family zinc finger 1 (FEZF1) as a potential regulator of early human neural development. FEZF1 is rapidly up-regulated during neural differentiation in hESCs and expressed before PAX6, a well-established marker of early human neural induction. We generated FEZF1-knockout H1 hESC lines using CRISPR-CAS9 technology and found that depletion of FEZF1 abrogates neural differentiation of hESCs. Moreover, loss of FEZF1 impairs the pluripotency exit of hESCs during neural specification, which partially explains the neural induction defect caused by FEZF1 deletion. However, enforced expression of FEZF1 itself fails to drive neural differentiation in hESCs, suggesting that FEZF1 is necessary but not sufficient for neural differentiation from hESCs. Taken together, our findings identify one of the earliest regulators expressed upon neural induction and provide insight into early neural development in human.

Models of gene gain and gene loss for probabilistic reconstruction of gene content in the last universal common ancestor of life.

Science.gov (United States)

Kannan, Lavanya; Li, Hua; Rubinstein, Boris; Mushegian, Arcady

2013-12-19

The problem of probabilistic inference of gene content in the last common ancestor of several extant species with completely sequenced genomes is: for each gene that is conserved in all or some of the genomes, assign the probability that its ancestral gene was present in the genome of their last common ancestor. We have developed a family of models of gene gain and gene loss in evolution, and applied the maximum-likelihood approach that uses phylogenetic tree of prokaryotes and the record of orthologous relationships between their genes to infer the gene content of LUCA, the Last Universal Common Ancestor of all currently living cellular organisms. The crucial parameter, the ratio of gene losses and gene gains, was estimated from the data and was higher in models that take account of the number of in-paralogs in genomes than in models that treat gene presences and absences as a binary trait. While the numbers of genes that are placed confidently into LUCA are similar in the ML methods and in previously published methods that use various parsimony-based approaches, the identities of genes themselves are different. Most of the models of either kind treat the genes found in many existing genomes in a similar way, assigning to them high probabilities of being ancestral ("high ancestrality"). The ML models are more likely than others to assign high ancestrality to the genes that are relatively rare in the present-day genomes.

Honey, Hadza, hunter-gatherers, and human evolution.

Science.gov (United States)

Marlowe, Frank W; Berbesque, J Colette; Wood, Brian; Crittenden, Alyssa; Porter, Claire; Mabulla, Audax

2014-06-01

Honey is the most energy dense food in nature. It is therefore not surprising that, where it exists, honey is an important food for almost all hunter-gatherers. Here we describe and analyze widespread honey collecting among foragers and show that where it is absent, in arctic and subarctic habitats, honey bees are also rare to absent. Second, we focus on one hunter-gatherer society, the Hadza of Tanzania. Hadza men and women both rank honey as their favorite food. Hadza acquire seven types of honey. Hadza women usually acquire honey that is close to the ground while men often climb tall baobab trees to raid the largest bee hives with stinging bees. Honey accounts for a substantial proportion of the kilocalories in the Hadza diet, especially that of Hadza men. Cross-cultural forager data reveal that in most hunter-gatherers, men acquire more honey than women but often, as with the Hadza, women do acquire some. Virtually all warm-climate foragers consume honey. Our closest living relatives, the great apes, take honey when they can. We suggest that honey has been part of the diet of our ancestors dating back to at least the earliest hominins. The earliest hominins, however, would have surely been less capable of acquiring as much honey as more recent, fully modern human hunter-gatherers. We discuss reasons for thinking our early ancestors would have acquired less honey than foragers ethnographically described, yet still significantly more than our great ape relatives. Copyright © 2014 Elsevier Ltd. All rights reserved.

'Special' non-human actors in the 'inclusive' early childhood classroom

DEFF Research Database (Denmark)

Watson, Karen; Millei, Zsuzsa; Petersen, Eva Bendix

2015-01-01

of classrooms. In this article, we pay attention to ‘special’ non-human actors present in an ‘inclusive’ early childhood classroom. These ‘special’ non-human actors are so named as they operate in the classroom as objects specific for the child with a diagnosis. The ‘special’ non-human actors, in the specific...... case the wrist band, the lock and the scooter board, take on meaning within discourses in the ‘inclusive’ classroom. We illuminate how these non-human actors contribute to the constitution of the ‘normal’ and the regulation of educators and children. To trouble the working of power and the control...

Early human symbolic behavior in the Late Pleistocene of Wallacea

Science.gov (United States)

Brumm, Adam; Hakim, Budianto; Ramli, Muhammad; Sumantri, Iwan; Burhan, Basran; Saiful, Andi Muhammad; Siagian, Linda; Suryatman; Sardi, Ratno; Jusdi, Andi; Abdullah; Mubarak, Andi Pampang; Hasliana; Hasrianti; Oktaviana, Adhi Agus; Adhityatama, Shinatria; van den Bergh, Gerrit D.; Aubert, Maxime; Zhao, Jian-xin; Huntley, Jillian; Li, Bo; Roberts, Richard G.; Saptomo, E. Wahyu; Perston, Yinika; Grün, Rainer

2017-01-01

Wallacea, the zone of oceanic islands separating the continental regions of Southeast Asia and Australia, has yielded sparse evidence for the symbolic culture of early modern humans. Here we report evidence for symbolic activity 30,000–22,000 y ago at Leang Bulu Bettue, a cave and rock-shelter site on the Wallacean island of Sulawesi. We describe hitherto undocumented practices of personal ornamentation and portable art, alongside evidence for pigment processing and use in deposits that are the same age as dated rock art in the surrounding karst region. Previously, assemblages of multiple and diverse types of Pleistocene “symbolic” artifacts were entirely unknown from this region. The Leang Bulu Bettue assemblage provides insight into the complexity and diversification of modern human culture during a key period in the global dispersal of our species. It also shows that early inhabitants of Sulawesi fashioned ornaments from body parts of endemic animals, suggesting modern humans integrated exotic faunas and other novel resources into their symbolic world as they colonized the biogeographically unique regions southeast of continental Eurasia. PMID:28373568

The origin of life and the last universal common ancestor: do we need a change of perspective?

Science.gov (United States)

Glansdorff, Nicolas; Xu, Ying; Labedan, Bernard

2009-09-01

A complete tree with roots, trunk and crown remains an appropriate model to represent all steps of life's development, from the emergence of a unique genetic code up to the last universal common ancestor and its further radiation. Catalytic closure of a mixture of prebiotic polymers is a heuristic alternative to the RNA world. Conjectures about emergence of life in an infinite multiverse should not confuse probability with possibility.

Accessibility of services for early infant diagnosis of Human ...

African Journals Online (AJOL)

Accessibility of services for early infant diagnosis of Human Immunodeficiency Virus in sub-Saharan Africa: a systematic review. ... infants who received a virological test within the first 2 months of life in sub-Saharan Africa varied from 3 to 58%, far below the 80% recommended level by the World Health Organization.

Most Compositae (Asteraceae) are descendants of a paleohexaploid and all share a paleotetraploid ancestor with the Calyceraceae.

Science.gov (United States)

Barker, Michael S; Li, Zheng; Kidder, Thomas I; Reardon, Chris R; Lai, Zhao; Oliveira, Luiz O; Scascitelli, Moira; Rieseberg, Loren H

2016-07-01

Like many other flowering plants, members of the Compositae (Asteraceae) have a polyploid ancestry. Previous analyses found evidence for an ancient duplication or possibly triplication in the early evolutionary history of the family. We sought to better place this paleopolyploidy in the phylogeny and assess its nature. We sequenced new transcriptomes for Barnadesia, the lineage sister to all other Compositae, and four representatives of closely related families. Using a recently developed algorithm, MAPS, we analyzed nuclear gene family phylogenies for evidence of paleopolyploidy. We found that the previously recognized Compositae paleopolyploidy is also in the ancestry of the Calyceraceae. Our phylogenomic analyses uncovered evidence for a successive second round of genome duplication among all sampled Compositae except Barnadesia. Our analyses of new samples with new tools provide a revised view of paleopolyploidy in the Compositae. Together with results from a high density Lactuca linkage map, our results suggest that the Compositae and Calyceraceae have a common paleotetraploid ancestor and that most Compositae are descendants of a paleohexaploid. Although paleohexaploids have been previously identified, this is the first example where the paleotetraploid and paleohexaploid lineages have survived over tens of millions of years. The complex polyploidy in the ancestry of the Compositae and Calyceraceae represents a unique opportunity to study the long-term evolutionary fates and consequences of different ploidal levels. © 2016 Botanical Society of America.

Immunohistochemical markers for corneal stem cells in the early developing human eye

DEFF Research Database (Denmark)

Lyngholm, Mikkel; Høyer, Poul E; Vorum, Henrik

2008-01-01

niche (week 14) in human embryos and fetuses. The expression of SOD2 and CK15 was investigated together with other recently identified limbal proteins. Previously suggested LSC and differentiation markers (PAX6, aquaporin-1 and nestin) were also investigated. Both SOD2 and CK15 were present...... markers and potential markers for LSCs and early transient amplifying cells in human adults. In this study, we describe the development of the ectodermally derived LSCs and the mesodermally derived niche cells from the time at which the cornea is defined (week 6) until the formation of the early limbal...

R-ES-ONANCE--IOc-tO-ber-19-9-7

Indian Academy of Sciences (India)

A clone refers to a population of cells or organisms which were derived asexually from a single ancestor. ... Hence, the nuclei from early embryos seemed to ... have come from a stem cell, which had ... It remains to be seen if a human adult.

Models of gene gain and gene loss for probabilistic reconstruction of gene content in the last universal common ancestor of life

Science.gov (United States)

2013-01-01

Background The problem of probabilistic inference of gene content in the last common ancestor of several extant species with completely sequenced genomes is: for each gene that is conserved in all or some of the genomes, assign the probability that its ancestral gene was present in the genome of their last common ancestor. Results We have developed a family of models of gene gain and gene loss in evolution, and applied the maximum-likelihood approach that uses phylogenetic tree of prokaryotes and the record of orthologous relationships between their genes to infer the gene content of LUCA, the Last Universal Common Ancestor of all currently living cellular organisms. The crucial parameter, the ratio of gene losses and gene gains, was estimated from the data and was higher in models that take account of the number of in-paralogs in genomes than in models that treat gene presences and absences as a binary trait. Conclusion While the numbers of genes that are placed confidently into LUCA are similar in the ML methods and in previously published methods that use various parsimony-based approaches, the identities of genes themselves are different. Most of the models of either kind treat the genes found in many existing genomes in a similar way, assigning to them high probabilities of being ancestral (“high ancestrality”). The ML models are more likely than others to assign high ancestrality to the genes that are relatively rare in the present-day genomes. Reviewers This article was reviewed by Martijn A Huynen, Toni Gabaldón and Fyodor Kondrashov. PMID:24354654

NKT cell depletion in humans during early HIV infection.

Science.gov (United States)

Fernandez, Caroline S; Kelleher, Anthony D; Finlayson, Robert; Godfrey, Dale I; Kent, Stephen J

2014-08-01

Natural killer T (NKT) cells bridge across innate and adaptive immune responses and have an important role in chronic viral infections such as human immunodeficiency virus (HIV). NKT cells are depleted during chronic HIV infection, but the timing, drivers and implications of this NKT cell depletion are poorly understood. We studied human peripheral blood NKT cell levels, phenotype and function in 31 HIV-infected subjects not on antiretroviral treatment from a mean of 4 months to 2 years after HIV infection. We found that peripheral CD4(+) NKT cells were substantially depleted and dysfunctional by 4 months after HIV infection. The depletion of CD4(+) NKT cells was more marked than the depletion of total CD4(+) T cells. Further, the early depletion of NKT cells correlated with CD4(+) T-cell decline, but not HIV viral levels. Levels of activated CD4(+) T cells correlated with the loss of NKT cells. Our studies suggest that the early loss of NKT cells is associated with subsequent immune destruction during HIV infection.

The human early-life exposome (HELIX): project rationale and design.

Science.gov (United States)

Vrijheid, Martine; 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; Gražulevičienė, 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

2014-06-01

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. 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. 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. 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.

Late Pleistocene climate drivers of early human migration

Science.gov (United States)

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.

New thinking: the evolution of human cognition

OpenAIRE

Heyes, Cecilia

2012-01-01

Humans are animals that specialize in thinking and knowing, and our extraordinary cognitive abilities have transformed every aspect of our lives. In contrast to our chimpanzee cousins and Stone Age ancestors, we are complex political, economic, scientific and artistic creatures, living in a vast range of habitats, many of which are our own creation. Research on the evolution of human cognition asks what types of thinking make us such peculiar animals, and how they have been generated by evolu...

The origin of snakes: revealing the ecology, behavior, and evolutionary history of early snakes using genomics, phenomics, and the fossil record.

Science.gov (United States)

Hsiang, Allison Y; Field, Daniel J; Webster, Timothy H; Behlke, Adam D B; Davis, Matthew B; Racicot, Rachel A; Gauthier, Jacques A

2015-05-20

The highly derived morphology and astounding diversity of snakes has long inspired debate regarding the ecological and evolutionary origin of both the snake total-group (Pan-Serpentes) and crown snakes (Serpentes). Although speculation abounds on the ecology, behavior, and provenance of the earliest snakes, a rigorous, clade-wide analysis of snake origins has yet to be attempted, in part due to a dearth of adequate paleontological data on early stem snakes. Here, we present the first comprehensive analytical reconstruction of the ancestor of crown snakes and the ancestor of the snake total-group, as inferred using multiple methods of ancestral state reconstruction. We use a combined-data approach that includes new information from the fossil record on extinct crown snakes, new data on the anatomy of the stem snakes Najash rionegrina, Dinilysia patagonica, and Coniophis precedens, and a deeper understanding of the distribution of phenotypic apomorphies among the major clades of fossil and Recent snakes. Additionally, we infer time-calibrated phylogenies using both new 'tip-dating' and traditional node-based approaches, providing new insights on temporal patterns in the early evolutionary history of snakes. Comprehensive ancestral state reconstructions reveal that both the ancestor of crown snakes and the ancestor of total-group snakes were nocturnal, widely foraging, non-constricting stealth hunters. They likely consumed soft-bodied vertebrate and invertebrate prey that was subequal to head size, and occupied terrestrial settings in warm, well-watered, and well-vegetated environments. The snake total-group - approximated by the Coniophis node - is inferred to have originated on land during the middle Early Cretaceous (~128.5 Ma), with the crown-group following about 20 million years later, during the Albian stage. Our inferred divergence dates provide strong evidence for a major radiation of henophidian snake diversity in the wake of the Cretaceous-Paleogene (K

Early androgen exposure and human gender development.

Science.gov (United States)

Hines, Melissa; Constantinescu, Mihaela; Spencer, Debra

2015-01-01

During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This

Body composition in Pan paniscus compared with Homo sapiens has implications for changes during human evolution.

Science.gov (United States)

Zihlman, Adrienne L; Bolter, Debra R

2015-06-16

The human body has been shaped by natural selection during the past 4-5 million years. Fossils preserve bones and teeth but lack muscle, skin, fat, and organs. To understand the evolution of the human form, information about both soft and hard tissues of our ancestors is needed. Our closest living relatives of the genus Pan provide the best comparative model to those ancestors. Here, we present data on the body composition of 13 bonobos (Pan paniscus) measured during anatomical dissections and compare the data with Homo sapiens. These comparative data suggest that both females and males (i) increased body fat, (ii) decreased relative muscle mass, (iii) redistributed muscle mass to lower limbs, and (iv) decreased relative mass of skin during human evolution. Comparison of soft tissues between Pan and Homo provides new insights into the function and evolution of body composition.

Incomplete lineage sorting patterns among human, chimpanzee and orangutan suggest recent orangutan speciation and widespread selection

DEFF Research Database (Denmark)

Hobolth, Asger; Dutheil, Julien; Hawks, John

2011-01-01

We search the complete orangutan genome for regions where humans are more closely related to orangutans than to chimpanzees due to incomplete lineage sorting (ILS) in the ancestor of human and chimpanzees. The search uses our recently developed coalescent HMM framework. We find ILS present in ~1%...

Evolution in a Contemporary Human Population: Intersexual Constraints and Costs of Reproduction

Energy Technology Data Exchange (ETDEWEB)

Stearns, Stephen [Yale University

2012-03-14

In this talk I will use an analysis of the population described in the Framingham Heart Study to make three points: (1) Contemporary humans are still evolving, and we can in part predict how they are responding to selection. (2) Selection on males and females differs, and its interaction with intersexual genetic correlations constrains the responses of each sex to selection. In other words, males are constrained by processes occurring in females, and females are constrained by processes occurring in males. (3) There are costs of reproduction in humans that are paid in lifespan, but it is likely that these costs were deferred to a point at which our ancestors would already have died for other reasons. When we detect those costs today, we find evidence that the versions of some genes that make us susceptible to cancer also increase reproductive success early in life. This confirms in humans a central assumption of the evolutionary theory of aging – the existence of genes that mediate a tradeoff between reproduction and survival - that had previously only been confirmed in model organisms like fruit flies and worms.

Four queries concerning the metaphysics of early human embryogenesis.

Science.gov (United States)

Howsepian, A A

2008-04-01

In this essay, I attempt to provide answers to the following four queries concerning the metaphysics of early human embryogenesis. (1) Following its first cellular fission, is it coherent to claim that one and only one of two "blastomeric" twins of a human zygote is identical with that zygote? (2) Following the fusion of two human pre-embryos, is it coherent to claim that one and only one pre-fusion pre-embryo is identical with that postfusion pre-embryo? (3) Does a live human being come into existence only when its brain comes into existence? (4) At implantation, does a pre-embryo become a mere part of its mother? I argue that either if things have quidditative properties or if criterialism is false, then queries (1) and (2) can be answered in the affirmative; that in light of recent developments in theories of human death and in light of a more "functional" theory of brains, query (3) can be answered in the negative; and that plausible mereological principles require a negative answer to query (4).

Phylogenetic analysis and victim contact tracing of rabies virus from humans and dogs in Bali, Indonesia.

Science.gov (United States)

Mahardika, G N K; Dibia, N; Budayanti, N S; Susilawathi, N M; Subrata, K; Darwinata, A E; Wignall, F S; Richt, J A; Valdivia-Granda, W A; Sudewi, A A R

2014-06-01

The emergence of human and animal rabies in Bali since November 2008 has attracted local, national and international interest. The potential origin and time of introduction of rabies virus to Bali is described. The nucleoprotein (N) gene of rabies virus from dog brain and human clinical specimens was sequenced using an automated DNA sequencer. Phylogenetic inference with Bayesian Markov Chain Monte Carlo (MCMC) analysis using the Bayesian Evolutionary Analysis by Sampling Trees (BEAST) v. 1.7.5 software confirmed that the outbreak of rabies in Bali was caused by an Indonesian lineage virus following a single introduction. The ancestor of Bali viruses was the descendant of a virus from Kalimantan. Contact tracing showed that the event most likely occurred in early 2008. The introduction of rabies into a large unvaccinated dog population in Bali clearly demonstrates the risk of disease transmission for government agencies and should lead to an increased preparedness and efforts for sustained risk reduction to prevent such events from occurring in future.

Microbiological evidence for Fe(III) reduction on early Earth

Science.gov (United States)

Vargas, Madeline; Kashefi, Kazem; Blunt-Harris, Elizabeth L.; Lovley, Derek R.

1998-09-01

It is generally considered that sulphur reduction was one of the earliest forms of microbial respiration, because the known microorganisms that are most closely related to the last common ancestor of modern life are primarily anaerobic, sulphur-reducing hyperthermophiles. However, geochemical evidence indicates that Fe(III) is more likely than sulphur to have been the first external electron acceptor of global significance in microbial metabolism. Here we show that Archaea and Bacteria that are most closely related to the last common ancestor can reduce Fe(III) to Fe(II) and conserve energy to support growth from this respiration. Surprisingly, even Thermotoga maritima, previously considered to have only a fermentative metabolism, could grow as a respiratory organism when Fe(III) was provided as an electron acceptor. These results provide microbiological evidence that Fe(III) reduction could have been an important process on early Earth and suggest that microorganisms might contribute to Fe(III) reduction in modern hot biospheres. Furthermore, our discovery that hyperthermophiles that had previously been thought to require sulphur for cultivation can instead be grown without the production of toxic and corrosive sulphide, should aid biochemical investigations of these poorly understood organisms.

Ancestor-descendant relationships in evolution: origin of the extant pygmy right whale, Caperea marginata.

Science.gov (United States)

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. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

The 3' region of Human Papillomavirus type 16 early mRNAs decrease expression

DEFF Research Database (Denmark)

Vinther, J.; Rosenstierne, M.W.; Kristiansen, Karen

2005-01-01

Background: High risk human papillomavirus (HR-HPV) infects mucosal surfaces and HR-HPV infection is required for development of cervical cancer. Accordingly, enforced expression of the early HR-HPV proteins can induce immortalisation of human cells. In most cervical cancers and cervical cancer...... cell lines the HR-HPV double stranded DNA genome has been integrated into the host cell genome. Methods: We have used a retroviral GUS reporter system to generate pools of stably transfected HaCaT and SiHa cells. The HPV-16 early sequences that are deleted upon integration of the HPV-16 genome...

The Bilingual Brain: Human Evolution and Second Language Acquisition

Directory of Open Access Journals (Sweden)

L. Kirk Hagen

2008-01-01

Full Text Available For the past half-century, psycholinguistic research has concerned itself with two mysteries of human cognition: (1 that children universally acquire a highly abstract, computationally complex set of linguistic rules rapidly and effortlessly, and (2 that second language acquisition (SLA among adults is, conversely, slow, laborious, highly variable, and virtually never results in native fluency. We now have a decent, if approximate, understanding of the biological foundations of first language acquisition, thanks in large part to Lenneberg's (1964, 1984 seminal work on the critical period hypothesis. More recently, the elements of a promising theory of language and evolution have emerged as well (see e.g. Bickerton, 1981, 1990; Leiberman, 1984, 1987. I argue here that the empirical foundations of an evolutionary theory of language are now solid enough to support an account of bilingualism and adult SLA as well. Specifically, I will show that evidence from the environment of evolutionary adaptation of paleolithic humans suggests that for our nomadic ancestors, the ability to master a language early in life was an eminently useful adaptation. However, the ability to acquire another language in adulthood was not, and consequently was not selected for propagation.

Structuring the analysis of human concerns at an early stage of system development

NARCIS (Netherlands)

Belyavin, A.J.; Tyler, S.; Lotens, W.A.

2011-01-01

This paper describes the development of a new approach to risk analysis applied to the investigation of how inserting new technologies in systems may induce positive and negative human impacts. The current approach employed by the UK Ministry of Defence, and embodied in the Early Human Factors

Early childhood development in Rwanda: a policy analysis of the human rights legal framework.

Science.gov (United States)

Binagwaho, Agnes; Scott, Kirstin W; Harward, Sardis H

2016-01-12

Early childhood development (ECD) is a critical period that continues to impact human health and productivity throughout the lifetime. Failing to provide policies and programs that support optimal developmental attainment when such services are financially and logistically feasible can result in negative population health, education and economic consequences that might otherwise be avoided. Rwanda, with its commitment to rights-based policy and program planning, serves as a case study for examination of the national, regional, and global human rights legal frameworks that inform ECD service delivery. In this essay, we summarize key causes and consequences of the loss of early developmental potential and how this relates to the human rights legal framework in Rwanda. We contend that sub-optimal early developmental attainment constitutes a violation of individuals' rights to health, education, and economic prosperity. These rights are widely recognized in global, regional and national human rights instruments, and are guaranteed by Rwanda's constitution. Recent policy implementation by several Rwandan ministries has increased access to health and social services that promote achievement of full developmental potential. These ECD-centric activities are characterized by an integrated approach to strengthening the services provided by several public sectors. Combining population level activities with those at the local level, led by local community health workers and women's councils, can bolster community education and ensure uptake of ECD services. Realization of the human rights to health, education, and economic prosperity requires and benefits from attention to the period of ECD, as early childhood has the potential to be an opportunity for expedient intervention or the first case of human rights neglect in a lifetime of rights violations. Efforts to improve ECD services and outcomes at the population level require multisector collaboration at the highest echelons

Earliest evidence of modern human life history in North African early Homo sapiens.

Science.gov (United States)

Smith, Tanya M; Tafforeau, Paul; Reid, Donald J; Grün, Rainer; Eggins, Stephen; Boutakiout, Mohamed; Hublin, Jean-Jacques

2007-04-10

Recent developmental studies demonstrate that early fossil hominins possessed shorter growth periods than living humans, implying disparate life histories. Analyses of incremental features in teeth provide an accurate means of assessing the age at death of developing dentitions, facilitating direct comparisons with fossil and modern humans. It is currently unknown when and where the prolonged modern human developmental condition originated. Here, an application of x-ray synchrotron microtomography reveals that an early Homo sapiens juvenile from Morocco dated at 160,000 years before present displays an equivalent degree of tooth development to modern European children at the same age. Crown formation times in the juvenile's macrodont dentition are higher than modern human mean values, whereas root development is accelerated relative to modern humans but is less than living apes and some fossil hominins. The juvenile from Jebel Irhoud is currently the oldest-known member of Homo with a developmental pattern (degree of eruption, developmental stage, and crown formation time) that is more similar to modern H. sapiens than to earlier members of Homo. This study also underscores the continuing importance of North Africa for understanding the origins of human anatomical and behavioral modernity. Corresponding biological and cultural changes may have appeared relatively late in the course of human evolution.

Early death, late death and repair factor in three human tumour cell lines

International Nuclear Information System (INIS)

Courdi, A.; Gioanni, J.; Mari, D.; Chauvel, P.

1997-01-01

The in vivo colony method used to generate survival curves following exposure to ionizing irradiation allows to score large clones, representing surviving cells, and small colonies, representing late reproductive death. By subtraction, early-dying cells can be estimated. In the three human tumour cell lines examined, we have observed that early cell death is a major mode of action of irradiation. The contribution of early cell death to total mortality increases as the dose increases. Moreover, repair due to dose-splitting and delayed plating in densely-inhibited cells is not observed in early-dying cells. (authors)

Cell-based interventions for neurologic conditions: ethical challenges for early human trials.

Science.gov (United States)

Mathews, D J H; Sugarman, J; Bok, H; Blass, D M; Coyle, J T; Duggan, P; Finkel, J; Greely, H T; Hillis, A; Hoke, A; Johnson, R; Johnston, M; Kahn, J; Kerr, D; Kurtzberg, J; Liao, S M; McDonald, J W; McKhann, G; Nelson, K B; Rao, M; Regenberg, A; Siegel, A W; Smith, K; Solter, D; Song, H; Vescovi, A; Young, W; Gearhart, J D; Faden, R

2008-07-22

Attempts to translate basic stem cell research into treatments for neurologic diseases and injury are well under way. With a clinical trial for one such treatment approved and in progress in the United States, and additional proposals under review, we must begin to address the ethical issues raised by such early forays into human clinical trials for cell-based interventions for neurologic conditions. An interdisciplinary working group composed of experts in neuroscience, cell biology, bioethics, law, and transplantation, along with leading disease researchers, was convened twice over 2 years to identify and deliberate on the scientific and ethical issues raised by the transition from preclinical to clinical research of cell-based interventions for neurologic conditions. While the relevant ethical issues are in many respects standard challenges of human subjects research, they are heightened in complexity by the novelty of the science, the focus on the CNS, and the political climate in which the science is proceeding. Distinctive challenges confronting US scientists, administrators, institutional review boards, stem cell research oversight committees, and others who will need to make decisions about work involving stem cells and their derivatives and evaluate the ethics of early human trials include evaluating the risks, safety, and benefits of these trials, determining and evaluating cell line provenance, and determining inclusion criteria, informed consent, and the ethics of conducting early human trials in the public spotlight. Further study and deliberation by stakeholders is required to move toward professional and institutional policies and practices governing this research.

The early noncoding region of human papillomavirus type 16 is regulated by cytoplasmic polyadenylation factors

DEFF Research Database (Denmark)

Glahder, Jacob-Andreas Harald; Kristiansen, Karen; Durand, Marjorie

2010-01-01

All human papillomavirus type 16 (HPV-16) early mRNAs are polyadenylated at the poly(A) signal within the early 3' untranslated region (3'UTR). The 3'end of the early E5 open reading frame and the 3'UTR of HPV-16 is very AU-rich, with five regions similar to cytoplasmic polyadenylation elements (...

Classification of human pathogen bacteria for early screening using electronic nose

Science.gov (United States)

Zulkifli, Syahida Amani; Mohamad, Che Wan Syarifah Robiah; Abdullah, Abu Hassan

2017-10-01

This paper present human pathogen bacteria for early screening using electronic nose. Electronic nose (E-nose) known as gas sensor array is a device that analyze the odor measurement give the fast response and less time consuming for clinical diagnosis. Many bacterial pathogens could lead to life threatening infections. Accurate and rapid diagnosis is crucial for the successful management of these infections disease. The conventional method need more time to detect the growth of bacterial. Alternatively, the bacteria are Pseudomonas aeruginosa and Shigella cultured on different media agar can be detected and classifies according to the volatile compound in shorter time using electronic nose (E-nose). Then, the data from electronic nose (E-nose) is processed using statistical method which is principal component analysis (PCA). The study shows the capability of electronic nose (E-nose) for early screening for bacterial infection in human stomach.

Strategies of Human Mating

Directory of Open Access Journals (Sweden)

David M. Buss

2006-12-01

Full Text Available Modern humans have inherited the mating strategies that led to the success of their ancestors. These strategies include long-term mating, short-term mating, extra-pair mating, mate poaching, and mate guarding. This article presents empirical evidence supporting evolution-based hypotheses about the complexities of these mating strategies. Since men and women historically confronted different adaptive problems in the mating domain, the sexes differ profoundly in evolved strategic solutions. These differences include possessing different mate preferences, different desires for short-term mating, and differences in the triggers that evoke sexual jealousy. The study of human mating is one of the “success stories” of evolutionary psychology.

Early modern human lithic technology from Jerimalai, East Timor.

Science.gov (United States)

Marwick, Ben; Clarkson, Chris; O'Connor, Sue; Collins, Sophie

2016-12-01

Jerimalai is a rock shelter in East Timor with cultural remains dated to 42,000 years ago, making it one of the oldest known sites of modern human activity in island Southeast Asia. It has special global significance for its record of early pelagic fishing and ancient shell fish hooks. It is also of regional significance for its early occupation and comparatively large assemblage of Pleistocene stone artefacts. Three major findings arise from our study of the stone artefacts. First, there is little change in lithic technology over the 42,000 year sequence, with the most noticeable change being the addition of new artefact types and raw materials in the mid-Holocene. Second, the assemblage is dominated by small chert cores and implements rather than pebble tools and choppers, a pattern we argue pattern, we argue, that is common in island SE Asian sites as opposed to mainland SE Asian sites. Third, the Jerimalai assemblage bears a striking resemblance to the assemblage from Liang Bua, argued by the Liang Bua excavation team to be associated with Homo floresiensis. We argue that the near proximity of these two islands along the Indonesian island chain (c.100 km apart), the long antiquity of modern human occupation in the region (as documented at Jerimalai), and the strong resemblance of distinctive flake stone technologies seen at both sites, raises the intriguing possibility that both the Liang Bua and Jerimalai assemblages were created by modern humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

The quantum defect: Early history and recent developments

International Nuclear Information System (INIS)

Rau, A.R.; Inokuti, M.

1997-01-01

The notion of the quantum defect is important in atomic and molecular spectroscopy and also in unifying spectroscopy with collision theory. In the latter context, the quantum defect may be viewed as an ancestor of the phase shift. However, the origin of the term open-quotes quantum defectclose quotes does not seem to be explained in standard textbooks. It occurred in a 1921 paper by Schroedinger, preceding quantum mechanics, yet giving the correct meaning as an index of the short-range interactions with the core of an atom. We present the early history of the quantum-defect idea, and sketch its recent developments. copyright 1997 American Association of Physics Teachers

Discontinuity of human presence at Atapuerca during the early Middle Pleistocene: a matter of ecological competition?

Science.gov (United States)

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.

Assembly of fibronectin into the extracellular matrix of early and late passage human skin fibroblasts

International Nuclear Information System (INIS)

Mann, D.M.

1987-01-01

The specific binding of soluble 125 I-human plasma fibronectin ( 125 I-HFN-P) to confluent cultures of early and late passage human skin fibroblasts was investigated. Previous studies HFN-P bound to fibroblast cell layers indicated that HNF-P was present in the cultures in two separate pools, distinguishable on the basis of their solubility in 1% deoxycholate. Examination of the kinetics of 125 I-HFN-P binding to Pool I of early and late passage cultures revealed that both cultures required 2-4 h to approach steady-state conditions. Other kinetic studies showed that the rates of low of 125 I-HFN-P from either Pool I or Pool II were similar for both cultures. Further, Scatchard analysis revealed a single class of Pool I binding sites with apparent dissociation constants (K/sub d/) of 5.3 x 10 -8 M (early passage) and 4.2 x 10 -8 M (late passage). These results indicate that early and late passage cultures of human fibroblasts exhibit differences in the number of cell surface biding sites for soluble fibronectin, and in the extent to which they incorporate soluble fibronectin into the extracellular matrix. Parameters which affect the fibronectin matrix assembly system of human skin fibroblasts were also examined. In addition, several monoclonal anti-fibronectin antibodies were characterized and developed as experimental probes for fibronectin structure and function

Experimental vitrification of human compacted morulae and early blastocysts using fine diameter plastic micropipettes.

Science.gov (United States)

Cremades, N; Sousa, M; Silva, J; Viana, P; Sousa, S; Oliveira, C; Teixeira da Silva, J; Barros, A

2004-02-01

Vitrification of human blastocysts has been successfully applied using grids, straws and cryoloops. We assessed the survival rate of human compacted morulae and early blastocysts vitrified in pipette tips with a smaller inner diameter and solution volume than the previously described open pulled straw (OPS) method. Excess day 5 human embryos (n = 63) were experimentally vitrified in vessels. Embryos were incubated at 37 degrees C with sperm preparation medium (SPM) for 1 min, SPM + 7.5% ethylene glycol (EG)/dimethylsulphoxide (DMSO) for 3 min, and SPM + 16.5% EG + 16.5% DMSO + 0.67 mol/l sucrose for 25 s. They were then aspirated (0.5 microl) into a plastic micropipette tip (0.36 mm inner diameter), exposed to liquid nitrogen (LN(2)) vapour for 2 min before being placed into a pre-cooled cryotube, which was then closed and plunged into LN(2). Embryos were warmed and diluted using 0.33 mol/l and 0.2 mol/l sucrose. The survival rate for compacted morulae was 73% (22/30) and 82% (27/33) for early blastocysts. The survival rates of human compacted morulae and early blastocysts after vitrification with this simple technique are similar to those reported in the literature achieved by slow cooling and other vitrification protocols.

Sexual size dimorphism, canine dimorphism, and male-male competition in primates: where do humans fit in?

Science.gov (United States)

Plavcan, J Michael

2012-03-01

Sexual size dimorphism is generally associated with sexual selection via agonistic male competition in nonhuman primates. These primate models play an important role in understanding the origins and evolution of human behavior. Human size dimorphism is often hypothesized to be associated with high rates of male violence and polygyny. This raises the question of whether human dimorphism and patterns of male violence are inherited from a common ancestor with chimpanzees or are uniquely derived. Here I review patterns of, and causal models for, dimorphism in humans and other primates. While dimorphism in primates is associated with agonistic male mate competition, a variety of factors can affect male and female size, and thereby dimorphism. The causes of human sexual size dimorphism are uncertain, and could involve several non-mutually-exclusive mechanisms, such as mate competition, resource competition, intergroup violence, and female choice. A phylogenetic reconstruction of the evolution of dimorphism, including fossil hominins, indicates that the modern human condition is derived. This suggests that at least some behavioral similarities with Pan associated with dimorphism may have arisen independently, and not directly from a common ancestor.

Epistatic adaptive evolution of human color vision.

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Shozo Yokoyama

2014-12-01

Full Text Available Establishing genotype-phenotype relationship is the key to understand the molecular mechanism of phenotypic adaptation. This initial step may be untangled by analyzing appropriate ancestral molecules, but it is a daunting task to recapitulate the evolution of non-additive (epistatic interactions of amino acids and function of a protein separately. To adapt to the ultraviolet (UV-free retinal environment, the short wavelength-sensitive (SWS1 visual pigment in human (human S1 switched from detecting UV to absorbing blue light during the last 90 million years. Mutagenesis experiments of the UV-sensitive pigment in the Boreoeutherian ancestor show that the blue-sensitivity was achieved by seven mutations. The experimental and quantum chemical analyses show that 4,008 of all 5,040 possible evolutionary trajectories are terminated prematurely by containing a dehydrated nonfunctional pigment. Phylogenetic analysis further suggests that human ancestors achieved the blue-sensitivity gradually and almost exclusively by epistasis. When the final stage of spectral tuning of human S1 was underway 45-30 million years ago, the middle and long wavelength-sensitive (MWS/LWS pigments appeared and so-called trichromatic color vision was established by interprotein epistasis. The adaptive evolution of human S1 differs dramatically from orthologous pigments with a major mutational effect used in achieving blue-sensitivity in a fish and several mammalian species and in regaining UV vision in birds. These observations imply that the mechanisms of epistatic interactions must be understood by studying various orthologues in different species that have adapted to various ecological and physiological environments.

Netrin-1, a urinary proximal tubular injury marker, is elevated early in the time course of human diabetes

NARCIS (Netherlands)

Jayakumar, Calpurnia; Nauta, Ferdau L.; Bakker, Stephan J. L.; Bilo, Henk; Gansevoort, Ron T.; Johnson, Maribeth H.; Ramesh, Ganesan

Netrin-1 was recently identified as an early diagnostic biomarker of chronic kidney disease (CKD) in an experimental animal model. However, its usefulness for early diagnosis of CKD in humans is unknown. The current study evaluated whether netrin-1 is increased in urine from human diabetic patients.

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

Science.gov (United States)

Yan, Shou-He

2013-09-01

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.

High adult mortality among Hiwi hunter-gatherers: implications for human evolution.

Science.gov (United States)

Hill, Kim; Hurtado, A M; Walker, R S

2007-04-01

Extant apes experience early sexual maturity and short life spans relative to modern humans. Both of these traits and others are linked by life-history theory to mortality rates experienced at different ages by our hominin ancestors. However, currently there is a great deal of debate concerning hominin mortality profiles at different periods of evolutionary history. Observed rates and causes of mortality in modern hunter-gatherers may provide information about Upper Paleolithic mortality that can be compared to indirect evidence from the fossil record, yet little is published about causes and rates of mortality in foraging societies around the world. To our knowledge, interview-based life tables for recent hunter-gatherers are published for only four societies (Ache, Agta, Hadza, and Ju/'hoansi). Here, we present mortality data for a fifth group, the Hiwi hunter-gatherers of Venezuela. The results show comparatively high death rates among the Hiwi and highlight differences in mortality rates among hunter-gatherer societies. The high levels of conspecific violence and adult mortality in the Hiwi may better represent Paleolithic human demographics than do the lower, disease-based death rates reported in the most frequently cited forager studies.

Global gene expression profiling of individual human oocytes and embryos demonstrates heterogeneity in early development.

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Lisa Shaw

Full Text Available 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.

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

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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.

2016-01-01

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

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

NARCIS (Netherlands)

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

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

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

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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

2014-10-03

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. Copyright © 2014, American Association for the Advancement of Science.

How hardwired is human behavior?

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Nicholson, N

1998-01-01

Time and time again managers have tried to eliminate hierarchies, politics, and interorganizational rivalry--but to no avail. Why? Evolutionary psychologists would say that they are working against nature--emotional and behavioral "hardwiring" that is the legacy of our Stone Age ancestors. In this evolutionary psychology primer for executives, Nigel Nicholson explores many of the Science's central tenets. Of course, evolutionary psychology is still an emerging discipline, and its strong connection with the theory of natural selection has sparked significant controversy. But, as Nicholson suggests, evolutionary psychology is now well established enough that its insights into human instinct will prove illuminating to anyone seeking to understand why people act the way they do in organizational settings. Take gossip. According to evolutionary psychology, our Stone Age ancestors needed this skill to survive the socially unpredictable conditions of the Savannah Plain. Thus, over time, the propensity to gossip became part of our mental programming. Executives trying to eradicate gossip at work might as well try to change their employees' musical tastes. Better to put one's energy into making sure the "rumor mill" avoids dishonesty or unkindness as much as possible. Evolutionary psychology also explores the dynamics of the human group. Clans on the Savannah Plain, for example, appear to have had no more than 150 members. The message for managers? People will likely be most effective in small organizational units. As every executive knows, it pays to be an insightful student of human nature. Evolutionary psychology adds another important chapter to consider.

Distinct GAGE and MAGE-A expression during early human development indicate specific roles in lineage differentiation

DEFF Research Database (Denmark)

Gjerstorff, Morten; Harkness, Linda; Kassem, Moustapha

2008-01-01

BACKGROUND: Expression of cancer/testis-associated proteins (CTAs) has traditionally been considered to be restricted to germ cells in normal tissues and to different types of malignancies. We have evaluated the potential role of CTAs in early human development. METHODS: Using immunohistochemistry...... and RT-PCR, we investigated the expression of CTAs in differentiated human embryonic stem cells (hESC) and in late embryos and early fetuses. RESULTS: We found that melanoma antigen A (MAGE-A) family members were expressed during differentiation of hESC to embryoid bodies and in teratomas, and overlapped...... with expression of the neuroectodermal markers beta-tubulin 3, Pax6 and nestin. A widespread expression of MAGE-A was also observed in neurons of the early developing central nervous system and peripheral nerves. G antigen (GAGE) expression was present in the early ectoderm of embryos, including cells...

Large number of ultraconserved elements were already present in the jawed vertebrate ancestor.

KAUST Repository

Wang, Jianli; Lee, Alison P; Kodzius, Rimantas; Brenner, Sydney; Venkatesh, Byrappa

2009-01-01

Stephen (2008) identified 13,736 ultraconserved elements (UCEs) in placental mammals and investigated their evolution in opossum, chicken, frog, and fugu. They found that there was a massive expansion of UCEs during tetrapod evolution and the substitution rate in UCEs showed a significant decline in tetrapods compared with fugu, suggesting they were exapted in tetrapods. They considered it unlikely that these elements are ancient but evolved at a higher rate in teleost fishes. In this study, we investigated the evolution of UCEs in a cartilaginous fish, the elephant shark and show that nearly half the UCEs were present in the jawed vertebrate ancestor. The substitution rate in UCEs is higher in fugu than in elephant shark, and approximately one-third of ancient UCEs have diverged beyond recognition in teleost fishes. These data indicate that UCEs have evolved at a higher rate in teleost fishes, which may have implications for their vast diversity and evolutionary success.

Large number of ultraconserved elements were already present in the jawed vertebrate ancestor.

KAUST Repository

Wang, Jianli

2009-03-01

Stephen (2008) identified 13,736 ultraconserved elements (UCEs) in placental mammals and investigated their evolution in opossum, chicken, frog, and fugu. They found that there was a massive expansion of UCEs during tetrapod evolution and the substitution rate in UCEs showed a significant decline in tetrapods compared with fugu, suggesting they were exapted in tetrapods. They considered it unlikely that these elements are ancient but evolved at a higher rate in teleost fishes. In this study, we investigated the evolution of UCEs in a cartilaginous fish, the elephant shark and show that nearly half the UCEs were present in the jawed vertebrate ancestor. The substitution rate in UCEs is higher in fugu than in elephant shark, and approximately one-third of ancient UCEs have diverged beyond recognition in teleost fishes. These data indicate that UCEs have evolved at a higher rate in teleost fishes, which may have implications for their vast diversity and evolutionary success.

Cytomolecular analysis of ribosomal DNA evolution in a natural allotetraploid Brachypodium hybridum and its putative ancestors – dissecting complex repetitive structure of intergenic spacers

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Natalia Borowska-Zuchowska

2016-10-01

Full Text Available Nucleolar dominance is an epigenetic phenomenon associated with nuclear 35S rRNA genes and consists in selective suppression of gene loci inherited from one of the progenitors in the allopolyploid. Our understanding of the exact mechanisms that determine this process is still fragmentary, especially in case of the grass species. This study aimed to shed some light on the molecular basis of this genome-specific inactivation of 35S rDNA loci in an allotetraploid Brachypodium hybridum (2n=30, which arose from the interspecific hybridization between two diploid ancestors that were very similar to modern B. distachyon (2n=10 and B. stacei (2n=20. Using fluorescence in situ hybridization with 25S rDNA and chromosome-specific BAC clones as probes we revealed that the nucleolar dominance is present not only in meristematic root-tip cells but also in differentiated cell fraction of B. hybridum. Additionally, the intergenic spacers (IGSs from both of the putative ancestors and the allotetraploid were sequenced and analyzed. The presumptive transcription initiation sites, spacer promoters and repeated elements were identified within the IGSs. Two different length variants, 2.3 kb and 3.5 kb, of IGSs were identified in B. distachyon and B. stacei, respectively, however only the IGS that had originated from B. distachyon-like ancestor was present in the allotetraploid. The amplification pattern of B. hybridum IGSs suggests that some genetic changes occurred in inactive B. stacei-like rDNA loci during the evolution of the allotetraploid. We hypothesize that their preferential silencing is an effect of structural changes in the sequence rather than just the result of the sole inactivation at the epigenetic level.

3D quantitative analysis of early decomposition changes of the human face.

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Caplova, Zuzana; Gibelli, Daniele Maria; Poppa, Pasquale; Cummaudo, Marco; Obertova, Zuzana; Sforza, Chiarella; Cattaneo, Cristina

2018-03-01

Decomposition of the human body and human face is influenced, among other things, by environmental conditions. The early decomposition changes that modify the appearance of the face may hamper the recognition and identification of the deceased. Quantitative assessment of those changes may provide important information for forensic identification. This report presents a pilot 3D quantitative approach of tracking early decomposition changes of a single cadaver in controlled environmental conditions by summarizing the change with weekly morphological descriptions. The root mean square (RMS) value was used to evaluate the changes of the face after death. The results showed a high correlation (r = 0.863) between the measured RMS and the time since death. RMS values of each scan are presented, as well as the average weekly RMS values. The quantification of decomposition changes could improve the accuracy of antemortem facial approximation and potentially could allow the direct comparisons of antemortem and postmortem 3D scans.

Archives and the Boundaries of Early Modern Science.

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Popper, Nicholas

2016-03-01

This contribution argues that the study of early modern archives suggests a new agenda for historians of early modern science. While in recent years historians of science have begun to direct increased attention toward the collections amassed by figures and institutions traditionally portrayed as proto-scientific, archives proliferated across early modern Europe, emerging as powerful tools for creating knowledge in politics, history, and law as well as natural philosophy, botany, and more. The essay investigates the methods of production, collection, organization, and manipulation used by English statesmen and Crown officers such as Keeper of the State Papers Thomas Wilson and Secretary of State Joseph Williamson to govern their disorderly collections. Their methods, it is shown, were shared with contemporaries seeking to generate and manage other troves of evidence and in fact reflect a complex ecosystem of imitation and exchange across fields of inquiry. These commonalities suggest that historians of science should look beyond the ancestors of modern scientific disciplines to examine how practices of producing knowledge emerged and migrated throughout cultures of learning in Europe and beyond. Creating such a map of knowledge production and exchange, the essay concludes, would provide a renewed and expansive ambition for the field.

Forces shaping the fastest evolving regions in the human genome

DEFF Research Database (Denmark)

Pollard, Katherine S; Salama, Sofie R; King, Bryan

2006-01-01

Comparative genomics allow us to search the human genome for segments that were extensively changed in the last approximately 5 million years since divergence from our common ancestor with chimpanzee, but are highly conserved in other species and thus are likely to be functional. We found 202...... genomic elements that are highly conserved in vertebrates but show evidence of significantly accelerated substitution rates in human. These are mostly in non-coding DNA, often near genes associated with transcription and DNA binding. Resequencing confirmed that the five most accelerated elements...... contributed to accelerated evolution of the fastest evolving elements in the human genome....

The Last Universal Common Ancestor: emergence, constitution and genetic legacy of an elusive forerunner

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Labedan Bernard

2008-07-01

Full Text Available Abstract 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

Early human-plant interactions based on palaeovegetation simulations of Africa over glacial-interglacial cycles

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Cowling, S. A.; Cox, P. M.; Jones, C. D.; Maslin, M. A.; Spall, S. A.

2003-04-01

A greater understanding of African palaeovegetation environments over the Pleistocene (1.6 Mya) is important for evaluating potential catalysts underlying the anatomical, social and demographic changes observed in early human populations. We used a state-of-the-art fully-coupled earth system model (HADLEY-GCM3) to simulate typical glacial and interglacial environments likely encountered by late-Pleistocene humans. Our simulations indicate that tropical broadleaf forests of central Africa were not severely restricted by expanding grasslands during the last glacial maximum, although the carbon content of stem and density of leaf components were substantially reduced. We interpret a natural eastern migration corridor between southern Africa and the Rift Valley based on simulations of a no-analogue vegetation assemblage characterised by a unique combination of grass and low density forest. We postulate that early human populations in southern Africa were isolated from northern groups during warm interglacials, and that trans-African migration was facilitated during glacial cycles via a more openly forested eastern corridor.

Sponge non-metastatic Group I Nme gene/protein - structure and function is conserved from sponges to humans

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2011-01-01

Background Nucleoside diphosphate kinases NDPK are evolutionarily conserved enzymes present in Bacteria, Archaea and Eukarya, with human Nme1 the most studied representative of the family and the first identified metastasis suppressor. Sponges (Porifera) are simple metazoans without tissues, closest to the common ancestor of all animals. They changed little during evolution and probably provide the best insight into the metazoan ancestor's genomic features. Recent studies show that sponges have a wide repertoire of genes many of which are involved in diseases in more complex metazoans. The original function of those genes and the way it has evolved in the animal lineage is largely unknown. Here we report new results on the metastasis suppressor gene/protein homolog from the marine sponge Suberites domuncula, NmeGp1Sd. The purpose of this study was to investigate the properties of the sponge Group I Nme gene and protein, and compare it to its human homolog in order to elucidate the evolution of the structure and function of Nme. Results We found that sponge genes coding for Group I Nme protein are intron-rich. Furthermore, we discovered that the sponge NmeGp1Sd protein has a similar level of kinase activity as its human homolog Nme1, does not cleave negatively supercoiled DNA and shows nonspecific DNA-binding activity. The sponge NmeGp1Sd forms a hexamer, like human Nme1, and all other eukaryotic Nme proteins. NmeGp1Sd interacts with human Nme1 in human cells and exhibits the same subcellular localization. Stable clones expressing sponge NmeGp1Sd inhibited the migratory potential of CAL 27 cells, as already reported for human Nme1, which suggests that Nme's function in migratory processes was engaged long before the composition of true tissues. Conclusions This study suggests that the ancestor of all animals possessed a NmeGp1 protein with properties and functions similar to evolutionarily recent versions of the protein, even before the appearance of true tissues

Brain anatomical networks in early human brain development.

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Fan, Yong; Shi, Feng; Smith, Jeffrey Keith; Lin, Weili; Gilmore, John H; Shen, Dinggang

2011-02-01

Recent neuroimaging studies have demonstrated that human brain networks have economic small-world topology and modular organization, enabling efficient information transfer among brain regions. However, it remains largely unknown how the small-world topology and modular organization of human brain networks emerge and develop. Using longitudinal MRI data of 28 healthy pediatric subjects, collected at their ages of 1 month, 1 year, and 2 years, we analyzed development patterns of brain anatomical networks derived from morphological correlations of brain regional volumes. The results show that the brain network of 1-month-olds has the characteristically economic small-world topology and nonrandom modular organization. The network's cost efficiency increases with the brain development to 1 year and 2 years, so does the modularity, providing supportive evidence for the hypothesis that the small-world topology and the modular organization of brain networks are established during early brain development to support rapid synchronization and information transfer with minimal rewiring cost, as well as to balance between local processing and global integration of information. Copyright © 2010. Published by Elsevier Inc.

Early Human Evolution in the Western Palaearctic: Ecological Scenarios

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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

Rates of morphological evolution are heterogeneous in Early Cretaceous birds

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Lloyd, Graeme T.

2016-01-01

The Early Cretaceous is a critical interval in the early history of birds. Exceptional fossils indicate that important evolutionary novelties such as a pygostyle and a keeled sternum had already arisen in Early Cretaceous taxa, bridging much of the morphological gap between Archaeopteryx and crown birds. However, detailed features of basal bird evolution remain obscure because of both the small sample of fossil taxa previously considered and a lack of quantitative studies assessing rates of morphological evolution. Here we apply a recently available phylogenetic method and associated sensitivity tests to a large data matrix of morphological characters to quantify rates of morphological evolution in Early Cretaceous birds. Our results reveal that although rates were highly heterogeneous between different Early Cretaceous avian lineages, consistent patterns of significantly high or low rates were harder to pinpoint. Nevertheless, evidence for accelerated evolutionary rates is strongest at the point when Ornithuromorpha (the clade comprises all extant birds and descendants from their most recent common ancestors) split from Enantiornithes (a diverse clade that went extinct at the end-Cretaceous), consistent with the hypothesis that this key split opened up new niches and ultimately led to greater diversity for these two dominant clades of Mesozoic birds. PMID:27053742

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

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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

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

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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…

Whole genome sequencing of Mycobacterium bovis to obtain molecular fingerprints in human and cattle isolates from Baja California, Mexico

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Sarai Estrella Sandoval-Azuara

2017-10-01

Conclusions: All isolates from humans had spoligotype patterns that matched those observed in the cattle isolates, and all human isolates shared common ancestors with cattle in Baja California based on SNP analysis. This suggests that most human tuberculosis caused by M. bovis in Baja California is derived from M. bovis circulating in Baja California cattle. These results reinforce the importance of bovine tuberculosis surveillance and control in this region.

Update of the human parvovirus B19 biology.

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Servant-Delmas, A; Morinet, F

2016-02-01

Since its discovery, the human parvovirus B19 (B19V) has been associated with many clinical situations in addition to the prototype clinical manifestations, i.e. erythema infectiosum and erythroblastopenia crisis. The clinical significance of the viral B19V DNA persistence in sera after acute infection remains largely unknown. Such data may constitute a new clinical entity and is discussed in this manuscript. In 2002, despite the genetic diversity among B19V viruses has been reported to be very low, the description of markedly distinct sequences showed a new organization into three genotypes. The most recent common ancestor for B19V genotypes was estimated at early 1800s. B19V replication is enhanced by hypoxia and this might to explain the high viral load detected by quantitative PCR in the sera of infected patients. The minimum infectious dose necessary to transmit B19V infection by the transfusion of labile blood products remains unclear. At the opposite, the US Food and Drug Administration proposed a limit of 10(4)IU/mL of viral DNA in plasma pools used for the production of plasma derivatives. Recently, a new human parvovirus (PARV4) has been discovered. The consequences on blood transfusion of this blood-borne agent and its pathogenicity are still unknown. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Dynamic expression of calretinin in embryonic and early fetal human cortex

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Miriam eGonzalez-Gomez

2014-06-01

Full Text Available 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 steps

Early-life adversity-induced long-term epigenetic programming associated with early onset of chronic physical aggression: Studies in humans and animals.

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Chistiakov, Dimitry A; Chekhonin, Vladimir P

2017-06-05

To examine whether chronic physical aggression (CPA) in adulthood can be epigenetically programmed early in life due to exposure to early-life adversity. Literature search of public databases such as PubMed/MEDLINE and Scopus. Children/adolescents susceptible for CPA and exposed to early-life abuse fail to efficiently cope with stress that in turn results in the development of CPA later in life. This phenomenon was observed in humans and animal models of aggression. The susceptibility to aggression is a complex trait that is regulated by the interaction between environmental and genetic factors. Epigenetic mechanisms mediate this interaction. Subjects exposed to stress early in life exhibited long-term epigenetic programming that can influence their behaviour in adulthood. This programming affects expression of many genes not only in the brain but also in other systems such as neuroendocrine and immune. The propensity to adult CPA behaviour in subjects experienced to early-life adversity is mediated by epigenetic programming that involves long-term systemic epigenetic alterations in a whole genome.

[Correlation between RNA Expression Level and Early PMI in Human Brain Tissue].

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Lü, Y H; Ma, K J; Li, Z H; Gu, J; Bao, J Y; Yang, Z F; Gao, J; Zeng, Y; Tao, L; Chen, L

2016-08-01

To explore the correlation between the expression levels of several RNA markers in human brain tissue and early postmortem interval （PMI）. Twelve individuals with known PMI （range from 4.3 to 22.5 h） were selected and total RNA was extracted from brain tissue. Eight commonly used RNA markers were chosen including β -actin, GAPDH, RPS29, 18S rRNA, 5S rRNA, U6 snRNA, miRNA-9 and miRNA-125b, and the expression levels were detected in brain tissue by real-time fluorescent quantitative PCR. The internal reference markers with stable expression in early PMI were screened using geNorm software and the relationship between its expression level and some relevant factors such as age, gender and cause of death were analyzed. RNA markers normalized by internal reference were inserted into the mathematic model established by previous research for PMI estimation using R software. Model quality was judged by the error rate calculated with estimated PMI. 5S rRNA, miRNA-9 and miRNA-125b showed quite stable expression and their expression levels had no relation with age, gender and cause of death. The error rate of estimated PMI using β -actin was 24.6%, while GAPDH was 41.0%. 5S rRNA, miRNA-9 and miRNA-125b are suitable as internal reference markers of human brain tissue owing to their stable expression in early PMI. The expression level of β -actin correlates well with PMI, which can be used as an additional index for early PMI estimation. Copyright© by the Editorial Department of Journal of Forensic Medicine

Chasing ghosts: allopolyploid origin of Oxyria sinensis (Polygonaceae) from its only diploid congener and an unknown ancestor.

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Luo, Xin; Hu, Quanjun; Zhou, Pingping; Zhang, Dan; Wang, Qian; Abbott, Richard J; Liu, Jianquan

2017-06-01

Reconstructing the origin of a polyploid species is particularly challenging when an ancestor has become extinct. Under such circumstances, the extinct donor of a genome found in the polyploid may be treated as a 'ghost' species in that its prior existence is recognized through the presence of its genome in the polyploid. In this study, we aimed to determine the polyploid origin of Oxyria sinensis (2n = 40) for which only one congeneric species is known, that is diploid O. digyna (2n = 14). Genomic in situ hybridization (GISH), transcriptome, phylogenetic and demographic analyses, and ecological niche modelling were conducted for this purpose. GISH revealed that O. sinensis comprised 14 chromosomes from O. digyna and 26 chromosomes from an unknown ancestor. Transcriptome analysis indicated that following divergence from O. digyna, involving genome duplication around 12 million years ago (Ma), a second genome duplication occurred approximately 6 Ma to give rise to O. sinensis. Oxyria sinensis was shown to contain homologous gene sequences divergent from those present in O. digyna in addition to a set that clustered with those in O. digyna. Coalescent simulations indicated that O. sinensis expanded its distribution approximately 6-7 Ma, possibly following the second polyploidization event, whereas O. digyna expanded its range much later. It was also indicated that the distributions of both species contracted and re-expanded during the Pleistocene climatic oscillations. Ecological niche modelling similarly suggested that both species experienced changes in their distributional ranges in response to Quaternary climatic changes. The extinction of the unknown 'ghost' tetraploid species implicated in the origin of O. sinensis could have resulted from superior adaptation of O. sinensis to repeated climatic changes in the region where it now occurs. © 2017 John Wiley & Sons Ltd.

Indigenous knowledge, belief and practice of wild plants among the Meru of Kenya : past and present human-plant relations in East Africa

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Ibui, Alfreda Kajira

2007-01-01

Humankind has resulted to the wild for food and medication since prehistory. Kenya for instance has been named the Cradle of Humankind due to the many findings by the Leakey family, where it has been confirmed that most of our early ancestors were gatherers. While this could be seen as a phenomenon

Three-dimensionally preserved minute larva of a great-appendage arthropod from the early Cambrian Chengjiang biota

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Liu, Yu; Melzer, Roland R.; Haug, Joachim T.; Haug, Carolin; Briggs, Derek E. G.; Hörnig, Marie K.; He, Yu-yang; Hou, Xian-guang

2016-05-01

A three-dimensionally preserved 2-mm-long larva of the arthropod Leanchoilia illecebrosa from the 520-million-year-old early Cambrian Chengjiang biota of China represents the first evidence, to our knowledge, of such an early developmental stage in a short-great-appendage (SGA) arthropod. The larva possesses a pair of three-fingered great appendages, a hypostome, and four pairs of well-developed biramous appendages. More posteriorly, a series of rudimentary limb Anlagen revealed by X-ray microcomputed tomography shows a gradient of decreasing differentiation toward the rear. This, and postembryonic segment addition at the putative growth zone, are features of late-stage metanauplii of eucrustaceans. L. illecebrosa and other SGA arthropods, however, are considered representative of early chelicerates or part of the stem lineage of all euarthropods. The larva of an early Cambrian SGA arthropod with a small number of anterior segments and their respective appendages suggests that posthatching segment addition occurred in the ancestor of Euarthropoda.

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

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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.

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

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Matthew W Self

2016-03-01

Full Text Available 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.

Transcriptional factor PU.1 regulates decidual C1q expression in early pregnancy in human

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Priyaa Madhukaran Raj

2015-02-01

Full Text Available 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. 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 dendritic cells 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.

The Australopithecines – An Extinct Group of Human Ancestors: My Scientific Interest in South Africa

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Kaszycka Katarzyna A.

2017-06-01

Full Text Available I introduce the subject of my research interest in South Africa - the australopithecines - a group of bipedal, small-brained and large-toothed creatures from the Plio-Pleistocene, from which the human genus arose. I then briefly discuss various topics of my research, concerning: (1 Taxonomic status and morphological description of the extinct human relative from the Kromdraai site (Australopithecus robustus; (2 Graphic reconstruction of the partial skull from Kromdraai - specimen numbered TM 1517; (3 Assessment of size sexual dimorphism of the South African australopithecines (Australopithecus robustus and Australopithecus africanus, which, in terms of facial features, was pronounced - being almost gorilla-sized; (4 Social behavior of a fossil hominid species from around 2 million years ago, which, in terms of the social structure, was most likely a multimale-multifemale one; and (5 An event from the history of paleoanthropology, concerning the content of the 1924/25 photographs of the Taung Child (Australopithecus africanus - the first australopithecine skull discovered.

Early Trypanosoma cruzi Infection Reprograms Human Epithelial Cells

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María Laura Chiribao

2014-01-01

Full Text Available 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.

Reconstructed ancestral Myo-inositol-3-phosphate synthases indicate that ancestors of the Thermococcales and Thermotoga species were more thermophilic than their descendants.

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Butzin, Nicholas C; Lapierre, Pascal; Green, Anna G; Swithers, Kristen S; Gogarten, J Peter; Noll, Kenneth M

2013-01-01

The bacterial genomes of Thermotoga species show evidence of significant interdomain horizontal gene transfer from the Archaea. Members of this genus acquired many genes from the Thermococcales, which grow at higher temperatures than Thermotoga species. In order to study the functional history of an interdomain horizontally acquired gene we used ancestral sequence reconstruction to examine the thermal characteristics of reconstructed ancestral proteins of the Thermotoga lineage and its archaeal donors. Several ancestral sequence reconstruction methods were used to determine the possible sequences of the ancestral Thermotoga and Archaea myo-inositol-3-phosphate synthase (MIPS). These sequences were predicted to be more thermostable than the extant proteins using an established sequence composition method. We verified these computational predictions by measuring the activities and thermostabilities of purified proteins from the Thermotoga and the Thermococcales species, and eight ancestral reconstructed proteins. We found that the ancestral proteins from both the archaeal donor and the Thermotoga most recent common ancestor recipient were more thermostable than their descendants. We show that there is a correlation between the thermostability of MIPS protein and the optimal growth temperature (OGT) of its host, which suggests that the OGT of the ancestors of these species of Archaea and the Thermotoga grew at higher OGTs than their descendants.

Reconstructed ancestral Myo-inositol-3-phosphate synthases indicate that ancestors of the Thermococcales and Thermotoga species were more thermophilic than their descendants.

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Nicholas C Butzin

Full Text Available The bacterial genomes of Thermotoga species show evidence of significant interdomain horizontal gene transfer from the Archaea. Members of this genus acquired many genes from the Thermococcales, which grow at higher temperatures than Thermotoga species. In order to study the functional history of an interdomain horizontally acquired gene we used ancestral sequence reconstruction to examine the thermal characteristics of reconstructed ancestral proteins of the Thermotoga lineage and its archaeal donors. Several ancestral sequence reconstruction methods were used to determine the possible sequences of the ancestral Thermotoga and Archaea myo-inositol-3-phosphate synthase (MIPS. These sequences were predicted to be more thermostable than the extant proteins using an established sequence composition method. We verified these computational predictions by measuring the activities and thermostabilities of purified proteins from the Thermotoga and the Thermococcales species, and eight ancestral reconstructed proteins. We found that the ancestral proteins from both the archaeal donor and the Thermotoga most recent common ancestor recipient were more thermostable than their descendants. We show that there is a correlation between the thermostability of MIPS protein and the optimal growth temperature (OGT of its host, which suggests that the OGT of the ancestors of these species of Archaea and the Thermotoga grew at higher OGTs than their descendants.

Microstructural Changes of the Human Brain from Early to Mid-Adulthood

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Lixia Tian

2017-08-01

Full Text Available Despite numerous studies on the microstructural changes of the human brain throughout life, we have indeed little direct knowledge about the changes from early to mid-adulthood. The aim of this study was to investigate the microstructural changes of the human brain from early to mid-adulthood. We performed two sets of analyses based on the diffusion tensor imaging (DTI data of 111 adults aged 18–55 years. Specifically, we first correlated age with skeletonized fractional anisotropy (FA, mean diffusivity (MD, axial diffusivity (AD and radial diffusivity (RD at global and regional level, and then estimated individuals’ ages based on each DTI metric using elastic net, a kind of multivariate pattern analysis (MVPA method that aims at selecting the model that achieves the best trade-off between goodness of fit and model complexity. We observed statistically significant negative age-vs-FA correlations and relatively less changes of MD. The negative age-vs-FA correlations were associated with negative age-vs-AD and positive age-vs-RD correlations. Regional negative age-vs-FA correlations were observed in the bilateral genu of the corpus callosum (CCg, the corticospinal tract (CST, the fornix and several other tracts, and these negative correlations may indicate the earlier changes of the fibers with aging. In brain age estimation, the chronological-vs-estimated-age correlations based on FA, MD, AD and RD were R = 0.62, 0.44, 0.63 and 0.69 (P = 0.002, 0.008, 0.002 and 0.002 based on 500 permutations, respectively, and these results indicate that even the microstructural changes from early to mid-adulthood alone are sufficiently specific to decode individuals’ ages. Overall, the current results not only demonstrated statistically significant FA decreases from early to mid-adulthood and clarified the driving factors of the FA decreases (RD increases and AD decreases, in contrast to increases of both measures in late-adulthood, but highlighted the

Microstructural Changes of the Human Brain from Early to Mid-Adulthood.

Science.gov (United States)

Tian, Lixia; Ma, Lin

2017-01-01

Despite numerous studies on the microstructural changes of the human brain throughout life, we have indeed little direct knowledge about the changes from early to mid-adulthood. The aim of this study was to investigate the microstructural changes of the human brain from early to mid-adulthood. We performed two sets of analyses based on the diffusion tensor imaging (DTI) data of 111 adults aged 18-55 years. Specifically, we first correlated age with skeletonized fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) at global and regional level, and then estimated individuals' ages based on each DTI metric using elastic net, a kind of multivariate pattern analysis (MVPA) method that aims at selecting the model that achieves the best trade-off between goodness of fit and model complexity. We observed statistically significant negative age-vs-FA correlations and relatively less changes of MD. The negative age-vs-FA correlations were associated with negative age-vs-AD and positive age-vs-RD correlations. Regional negative age-vs-FA correlations were observed in the bilateral genu of the corpus callosum (CCg), the corticospinal tract (CST), the fornix and several other tracts, and these negative correlations may indicate the earlier changes of the fibers with aging. In brain age estimation, the chronological-vs-estimated-age correlations based on FA, MD, AD and RD were R = 0.62, 0.44, 0.63 and 0.69 ( P = 0.002, 0.008, 0.002 and 0.002 based on 500 permutations), respectively, and these results indicate that even the microstructural changes from early to mid-adulthood alone are sufficiently specific to decode individuals' ages. Overall, the current results not only demonstrated statistically significant FA decreases from early to mid-adulthood and clarified the driving factors of the FA decreases (RD increases and AD decreases, in contrast to increases of both measures in late-adulthood), but highlighted the necessity of

The origins of human parasites: Exploring the evidence for endoparasitism throughout human evolution.

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Mitchell, Piers D

2013-09-01

It is important to determine the origins of human parasites if we are to understand the health of past populations and the effects of parasitism upon human evolution. It also helps us to understand emerging infectious diseases and the modern clinical epidemiology of parasites. This study aims to distinguish those heirloom parasites that have infected humans and their ancestors throughout their evolution in Africa from those recent souvenir species to which humans have only become exposed following contact with animals during their migration across the globe. Ten such heirloom parasites are proposed, which appear to have been spread across the globe. Six further heirlooms are noted to have limited spread due to the constraints of their life cycle. Twelve souvenir parasites of humans are described, along with their animal reservoirs. While the origins of 28 species of endoparasite have been determined, many more species require further assessment once a more systematic analysis of ancient parasites in other regions of Africa has been undertaken. Copyright © 2013 Elsevier Inc. All rights reserved.

Variable postpartum responsiveness among humans and other primates with "cooperative breeding": A comparative and evolutionary perspective.

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Hrdy, Sarah B

2016-01-01

This article is part of a Special Issue "Parental Care".Until recently, evolutionists reconstructing mother-infant bonding among human ancestors relied on nonhuman primate models characterized by exclusively maternal care, overlooking the highly variable responsiveness exhibited by mothers in species with obligate reliance on allomaternal care and provisioning. It is now increasingly recognized that apes as large-brained, slow maturing, and nutritionally dependent for so long as early humans were, could not have evolved unless "alloparents" (group members other than genetic parents), in addition to parents, had helped mothers to care for and provision offspring, a rearing system known as "cooperative breeding." Here I review situation-dependent maternal responses ranging from highly possessive to permissive, temporarily distancing, rejecting, or infanticidal, documented for a small subset of cooperatively breeding primates. As in many mammals, primate maternal responsiveness is influenced by physical condition, endocrinological priming, prior experience and local environments (especially related to security). But mothers among primates who evolved as cooperative breeders also appear unusually sensitive to cues of social support. In addition to more "sapient" or rational decision-making, humankind's deep history of cooperative breeding must be considered when trying to understand the extremely variable responsiveness of human mothers. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic Differences Between Humans and Great Apes -- Implications for the Evolution of Humans

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Varki, Ajit

2004-06-01

At the level of individual protein sequences, humans are 97-100% identical to the great apes, our closest evolutionary relatives. The evolution of humans (and of human intelligence) from a common ancestor with the chimpanzee and bonobo involved many steps, influenced by interactions amongst factors of genetic, developmental, ecological, microbial, climatic, behavioral, cultural and social origin. The genetic factors can be approached by direct comparisons of human and great ape genomes, genes and gene products, and by elucidating biochemical and biological consequences of any differences found. We have discovered multiple genetic and biochemical differences between humans and great apes, particularly with respect to a family of cell surface molecules called sialic acids, as well as in the metabolism of thyroid hormones. The hormone differences have potential consequences for human brain development. The differences in sialic acid biology have multiple implications for the human condition, ranging from susceptibility or resistance to microbial pathogens, effects on endogenous receptors in the immune system, and potential effects on placental signaling, expression of oncofetal antigens in cancers, consequences of dietary intake of animal foods, and development of the mammalian brain.

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

Science.gov (United States)

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…

Convergent evolution of Hawaiian and Australo-Pacific honeyeaters from distant songbird ancestors.

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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.

Activation of PPAR{gamma} by Human Cytomegalovirus for de novo Replication Impairs Migration and Invasiveness of Cytotrophoblast from Early Placenta

DEFF Research Database (Denmark)

Rauwel, Benjamin; Mariamé, Bernard; Martin, Hélène

2010-01-01

, as assessed by using well-established in vitro models of invasive trophoblast i.e. primary cultures of EVCT isolated from first trimester placentas and the EVCT-derived cell line HIPEC. Our data provide new clues to explain how early infection during pregnancy could impair implantation, placentation...... and chromatin immunoprecipitation assays. Due to the key role of PPARgamma in placentation and its specific trophoblast expression within the human placenta, we then provided evidence that by activating PPARgamma human cytomegalovirus dramatically impaired early human trophoblast migration and invasiveness...

Reconstructing a B-cell clonal lineage. I. Statistical inference of unobserved ancestors [v1; ref status: indexed, http://f1000r.es/z6

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Thomas B Kepler

2013-04-01

Full Text Available One of the key phenomena in the adaptive immune response to infection and immunization is affinity maturation, during which antibody genes are mutated and selected, typically resulting in a substantial increase in binding affinity to the eliciting antigen. Advances in technology on several fronts have made it possible to clone large numbers of heavy-chain light-chain pairs from individual B cells and thereby identify whole sets of clonally related antibodies. These collections could provide the information necessary to reconstruct their own history - the sequence of changes introduced into the lineage during the development of the clone - and to study affinity maturation in detail. But the success of such a program depends entirely on accurately inferring the founding ancestor and the other unobserved intermediates. Given a set of clonally related immunoglobulin V-region genes, the method described here allows one to compute the posterior distribution over their possible ancestors, thereby giving a thorough accounting of the uncertainty inherent in the reconstruction. I demonstrate the application of this method on heavy-chain and light-chain clones, assess the reliability of the inference, and discuss the sources of uncertainty.

Early adolescent childbearing in low- and middle-income countries: associations with income inequity, human development and gender equality.

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Decker, Michele R; Kalamar, Amanda; Tunçalp, Özge; Hindin, Michelle J

2017-03-01

Reducing unwanted adolescent childbearing is a global priority. Little is known about how national-level economic and human development indicators relate to early adolescent childbearing. This ecological study evaluates associations of Gross Domestic Product (GDP), GINI index, Human Development Index (HDI) and Gender-related Development Index (GDI; i.e. the HDI adjusted for gender disparities) with early adolescent childbearing in 27 low- and middle-income countries (LMICs) across three time periods. Among women ages 18–24, prevalence estimates for early birth (development adjusted for gender disparities in educational and economic prospects, was more consistently related to early adolescent childbearing than the absolute development prospects as given by the HDI. While creating gender equality is an important goal in and of itself, the findings emphasize the potential for improved national-level gender equitable development as a means to improve adolescents’ sexual and reproductive health.

From Fertilisation to Implantation in Mammalian Pregnancy—Modulation of Early Human Reproduction by the Endocannabinoid System

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Justin C. Konje

2010-09-01

Full Text Available There is an increasing recognition that the endocannabinoid system is the crucial cytokine-hormone system regulating early human pregnancy. The synchronous development of the fertilized embryo and the endometrium to ensure timely implantation has been shown to be one of the pivotal steps to successful implantation. This development is thought to be regulated by a finely balanced relationship between various components of the endocannabinoid system in the endometrium, the embryo and the Fallopian tube. In addition, this system has also been shown to be involved in the regulation of the development and maturation of the gametes prior to fertilization. In this review, we will examine the evidence from animal and human studies to support the role of the endocannabinoid system in gametogenesis, fertilization, implantation, early pregnancy maintenance, and in immunomodulation of pregnancy. We will discuss the role of the cannabinoid receptors and the enzymes involved in the synthesis and degradation of the key endocannabinoid ligands (e.g., anandamide and 2-arachinoylglycerol in early reproduction.

On The Evolution of Human Jaws and Teeth: A Review

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Serhat Yalcin

2011-06-01

Full Text Available The jaws and teeth of Homo sapiens have evolved, from the last common ancestor of chimpanzee and men to their current form. Many factors such as the foods eaten and the processing of foods by fire and tools have effected this evolution course. The evolution of the masticatory complex is related to other anatomical features such as brain size and bipedal posture, and leads to important proceedings like the formation of speech and language. In this review, the evolution of human jaws and teeth and its impact on the general course of human evolution is discussed.

Evidence supporting a zoonotic origin of human coronavirus strain NL63.

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

2012-12-01

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

Signatures of Climatic Change In Human Mitochondrial Dna From Europe

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Richards, M. B.; Macaulay, V. A.; Torroni, A.; Bandelt, H.-J.

Founder analysis is an approach to analysing non-recombining DNA sequence data, such as variation in the mitochondrial DNA (mtDNA), which aims at identifying and dating migrations into new territory. We applied the approach to about 4,000 human mtDNA sequences from Europe and the Near East, in order to estimate the proportion of modern lineages whose ancestors arrived at various times during the continent's past. We found that the major signal dates to about 15,000 years ago, at the time of rewarming following the Last Glacial Maximum (LGM). There is little or no archaeological evidence for immigration into Europe at this time, and the record indicates that at least parts of southern Europe remained populated during the LGM. Therefore, we interpret this signal as the trace of a bottleneck at the time of the LGM, as a result of the retreat from northern Europe during the peak of the glaciation, followed by a re-expansion from one or more refugial zones. Immigration episodes then figure at the beginning of the Early Upper Palaeolithic, during the Middle Upper Palaeolithic, and with the Neolithic. The impact of the latter on the composition of the European mtDNA pool was evidently rather minor. This result implies that climate is likely to have been a major force shaping human demographic history in Europe.

UVA phototransduction drives early melanin synthesis in human melanocytes.

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Wicks, Nadine L; Chan, Jason W; Najera, Julia A; Ciriello, Jonathan M; Oancea, Elena

2011-11-22

Exposure of human skin to solar ultraviolet radiation (UVR), a powerful carcinogen [1] comprising ~95% ultraviolet A (UVA) and ~5% ultraviolet B (UVB) at the Earth's surface, promotes melanin synthesis in epidermal melanocytes [2, 3], which protects skin from DNA damage [4, 5]. UVB causes DNA lesions [6] that lead to transcriptional activation of melanin-producing enzymes, resulting in delayed skin pigmentation within days [7]. In contrast, UVA causes primarily oxidative damage [8] and leads to immediate pigment darkening (IPD) within minutes, via an unknown mechanism [9, 10]. No receptor protein directly mediating phototransduction in skin has been identified. Here we demonstrate that exposure of primary human epidermal melanocytes (HEMs) to UVA causes calcium mobilization and early melanin synthesis. Calcium responses were abolished by treatment with G protein or phospholipase C (PLC) inhibitors or by depletion of intracellular calcium stores. We show that the visual photopigment rhodopsin [11] is expressed in HEMs and contributes to UVR phototransduction. Upon UVR exposure, significant melanin production was measured within one hour; cellular melanin continued to increase in a retinal- and calcium-dependent manner up to 5-fold after 24 hr. Our findings identify a novel UVA-sensitive signaling pathway in melanocytes that leads to calcium mobilization and melanin synthesis and may underlie the mechanism of IPD in human skin. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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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…

Before the Emergence of Homo sapiens: Overview on the Early-to-Middle Pleistocene Fossil Record (with a Proposal about Homo heidelbergensis at the subspecific level)

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Manzi, Giorgio

2011-01-01

The origin of H. sapiens has deep roots, which include two crucial nodes: (1) the emergence and diffusion of the last common ancestor of later Homo (in the Early Pleistocene) and (2) the tempo and mode of the appearance of distinct evolutionary lineages (in the Middle Pleistocene). The window between 1,000 and 500 thousand years before present appears of crucial importance, including the generation of a new and more encephalised kind of humanity, referred to by many authors as H. heidelbergensis. This species greatly diversified during the Middle Pleistocene up to the formation of new variants (i.e., incipient species) that, eventually, led to the allopatric speciation of H. neanderthalensis and H. sapiens. The special case furnished by the calvarium found near Ceprano (Italy), dated to 430–385 ka, offers the opportunity to investigate this matter from an original perspective. It is proposed to separate the hypodigm of a single, widespread, and polymorphic human taxon of the Middle Pleistocene into distinct subspecies (i.e., incipient species). The ancestral one should be H. heidelbergensis, including specimens such as Ceprano and the mandible from Mauer. PMID:21716742

Buoyancy differences among two deepwater ciscoes from the Great Lakes and their putative ancestor

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Krause, A.E.; Eshenroder, R.L.; Begnoche, L.J.

2002-01-01

We analyzed buoyancy in two deepwater ciscoes, Coregonus hoyi and C. kiyi, and in C. artedi, their putative ancestor, and also analyzed how variations in fish weight, water content, and lipid content affected buoyancy. Buoyancy was significantly different among the three species (p < 0.0001). Estimates of percent buoyancy (neutral buoyancy = 0.0%) were: kiyi, 3.8%; hoyi, 4.7%; and artedi, 5.7%. Buoyancy did not change with fish weight alone (p = 0.38). Fish weight was negatively related to water content for all three species (p = 0.037). Lipid content was not significantly different between hoyi and kiyi, but artedi had significantly fewer lipids than hoyi and kiyi (p < 0.10). When artedi was removed from the analysis, fish weight and lipids accounted for 48% of the variation in buoyancy (p = 0.003), fatter hoyi were less dense than leaner hoyi, but fatter and leaner kiyi were no different in density. Our findings provide additional evidence that buoyancy regulation was a speciating mechanism in deepwater ciscoes and that kiyi is more specialized than hoyi for diel-vertical migration in deep water.

Early Menarche as an Alternative Reproductive Tactic in Human Females: An Evolutionary Approach to Reproductive Health Issues

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Meghan T. Gillette

2012-12-01

Full Text Available The age at which a female reaches sexual maturity is critical in determining her future reproductive health and success. Thus, a worldwide decline in menarcheal age (timing of first menstrual period may have serious long-term consequences. Early menarcheal timing (first menstrual period before age 12 can have a negative effect on fecundity, as well as the quality and quantity of offspring, and may consequently influence population growth or decline. In this paper, we apply an evolutionary framework to modern human health, and assess both proximate and ultimate consequences of declining menarcheal age. Examination of human reproductive health within an evolutionary framework is innovative and essential, because it illuminates the ultimate consequences of a declining age of menarche and facilitates new ways of thinking about the long-term and intergenerational transmission of health and disease; thus, an evolutionary framework lends itself to innovative public health and policy programs. In this paper, we examine whether or not early menarche is an alternative reproductive tactic that modern human females employ in response to a stressful environment, and whether or not early menarche is ultimately beneficial.

From the Cult of the “Self” to the Ancestor Cult: Trilogy The Cult of the Self by Maurice Barrés

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Vera V. Shervashidze

2016-09-01

Full Text Available The debut of Maurice Barrès, his trilogy The Cult of the Self immediately won the reader’s attention. In the 1890s, his works evoked increasing interest. His contemporaries read them as a fascinating narrative about the drama of European consciousness and the attempts to overcome this drama. However, after the author’s death, the interest of readers and researchers to his works decreased that may be explained by his fascination with ideas of nationalism, or boulangisme, especially during the war. The writer was accused of nationalism, however his nationalism was but a “replica” of his early ideas about the “culture” of “the self.” According to Barrès, all major themes of his work were reflected in the first trilogy of The Cult of the Self. Later in his career, revealing the typological similarity of the processes taking place in the inner “self” and within the nation, he wrote about degradation of the “self” and degradation of the nation in parallel. Portraying “the disease of the century” and seeking its recovery, Barrès introduced the theme of the ancestor cult as a means of moral redemption in his late work. The present study of linguistic, cultural, and historical properties of Barrès’s work intends to introduce one of the greatest turn-of-the-century writers into the Russian academic context.

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

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

2010-03-01

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

Defining the genomic signature of totipotency and pluripotency during early human development.

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Amparo Galan

Full Text Available 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.

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

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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…

Early embryonic chromosome instability results in stable mosaic pattern in human tissues.

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Hasmik Mkrtchyan

Full Text Available The discovery of copy number variations (CNV in the human genome opened new perspectives on the study of the genetic causes of inherited disorders and the aetiology of common diseases. Here, a single-cell-level investigation of CNV in different human tissues led us to uncover the phenomenon of mitotically derived genomic mosaicism, which is stable in different cell types of one individual. The CNV mosaic ratios were different between the 10 individuals studied. However, they were stable in the T lymphocytes, immortalized B lymphoblastoid cells, and skin fibroblasts analyzed in each individual. Because these cell types have a common origin in the connective tissues, we suggest that mitotic changes in CNV regions may happen early during embryonic development and occur only once, after which the stable mosaic ratio is maintained throughout the differentiated tissues. This concept is further supported by a unique study of immortalized B lymphoblastoid cell lines obtained with 20 year difference from two subjects. We provide the first evidence of somatic mosaicism for CNV, with stable variation ratios in different cell types of one individual leading to the hypothesis of early embryonic chromosome instability resulting in stable mosaic pattern in human tissues. This concept has the potential to open new perspectives in personalized genetic diagnostics and can explain genetic phenomena like diminished penetrance in autosomal dominant diseases. We propose that further genomic studies should focus on the single-cell level, to better understand the aetiology of aging and diseases mediated by somatic mutations.

A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD

DEFF Research Database (Denmark)

Fujihara, Masashi; Bartels, Emil; Nielsen, Lars B

2009-01-01

changes consistent with early human AMD including loss of basal infoldings and accumulation of cytoplasmic vacuoles in the RPE, and basal laminar deposits containing long-spacing collagen and heterogeneous debris in Bruch membrane of apoB100 mice. In apoB100 mice given a high-fat diet, basal linear...... transgenic for a human genomic fragment encoding the full length human apoB ("apoB100" mice) and litter-mate control mice were given a normal chow or high-fat diet for 12 months. Mice were evaluated for human apoB mRNA expression in the RPE/choroid and liver by RT-qPCR. Phenotypic changes associated......-like deposits were identified in 12-month-old mice. Linear regression analysis showed that the genotype (human apoB transgene) was a stronger influencing factor than high-fat diet in producing AMD-like lesions used in this study. Human apoB100 transgenic mice overexpress apoB in RPE and, with time, develop...

Analysis of early thrombus dynamics in a humanized mouse laser injury model.

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Wang, Weiwei; Lindsey, John P; Chen, Jianchun; Diacovo, Thomas G; King, Michael R

2014-01-01

Platelet aggregation and thrombus formation at the site of injury is a dynamic process that involves the continuous addition of new platelets as well as thrombus rupture. In the early stages of hemostasis (within minutes after vessel injury) this process can be visualized by transfusing fluorescently labeled human platelets and observing their deposition and detachment. These two counterbalancing events help the developing thrombus reach a steady-state morphology, where it is large enough to cover the injured vessel surface but not too large to form a severe thrombotic occlusion. In this study, the spatial and temporal aspects of early stage thrombus dynamics which result from laser-induced injury on arterioles of cremaster muscle in the humanized mouse were visualized using fluorescent microscopy. It was found that rolling platelets show preference for the upstream region while tethering/detaching platelets were primarily found downstream. It was also determined that the platelet deposition rate is relatively steady, whereas the effective thrombus coverage area does not increase at a constant rate. By introducing a new method to graphically represent the real time in vivo physiological shear stress environment, we conclude that the thrombus continuously changes shape by regional growth and decay, and neither dominates in the high shear stress region.

Population genetics of foxtail millet and its wild ancestor

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Wang Yongfang

2010-10-01

Full Text Available Abstract Background Foxtail millet (Setaria italica (L. P. Beauv., one of the most ancient domesticated crops, is becoming a model system for studying biofuel crops and comparative genomics in the grasses. However, knowledge on the level of genetic diversity and linkage disequilibrium (LD is very limited in this crop and its wild ancestor, green foxtail (Setaria viridis (L. P. Beauv.. Such information would help us to understand the domestication process of cultivated species and will allow further research in these species, including association mapping and identification of agricultural significant genes involved in domestication. Results In this study, we surveyed DNA sequence for nine loci across 50 accessions of cultivated foxtail millet and 34 of its wild progenitor. We found a low level of genetic diversity in wild green foxtail (θ = 0.0059, θ means Watterson's estimator of θ. Despite of a 55% loss of its wild diversity, foxtail millet still harbored a considerable level of diversity (θ = 0.0027 when compared to rice and sorghum (θ = 0.0024 and 0.0034, respectively. The level of LD in the domesticated foxtail millet extends to 1 kb, while it decayed rapidly to a negligible level within 150 bp in wild green foxtail. Using coalescent simulation, we estimated the bottleneck severity at k = 0.6095 when ρ/θ = 1. These results indicated that the domestication bottleneck of foxtail millet was more severe than that of maize but slightly less pronounced than that of rice. Conclusions The results in this study establish a general framework for the domestication history of foxtail millet. The low level of genetic diversity and the increased level of LD in foxtail millet are mainly caused by a population bottleneck, although gene flow from foxtail millet to green foxtail is another factor that may have shaped the pattern of genetic diversity of these two related gene pools. The knowledge provided in this study will benefit future population

Rooting human parechovirus evolution in time

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Benschop Kimberley

2009-07-01

Full Text Available Abstract Background The Picornaviridae family contains a number of important pathogenic viruses, among which the recently reclassified human parechoviruses (HPeVs. These viruses are widespread and can be grouped in several types. Understanding the evolutionary history of HPeV could answer questions such as how long the circulating lineages last shared a common ancestor and how the evolution of this viral species is shaped by its population dynamics. Using both strict and relaxed clock Bayesian phylogenetics we investigated 1 the substitutions rates of the structural P1 and capsid VP1 regions and 2 evolutionary timescale of currently circulating HPeV lineages. Results Our estimates reveal that human parechoviruses exhibit high substitution rates for both structural P1 and capsid VP1 regions, respectively 2.21 × 10-3 (0.48 – 4.21 × 10-3 and 2.79 × 10-3 (2.05 – 3.66 × 10-3 substitutions per site per year. These are within the range estimated for other picornaviruses. By employing a constant population size coalescent prior, the date of the most recent common ancestor was estimated to be at around 1600 (1427–1733. In addition, by looking at the frequency of synonymous and non-synonymous substitutions within the VP1 gene we show that purifying selection constitutes the dominating evolutionary force leading to strong amino acid conservation. Conclusion In conclusion, our estimates provide a timescale for the evolution of HPeVs and suggest that genetic diversity of current circulating HPeV types has arisen about 400 years ago.

Evolutionary history of Helicobacter pylori sequences reflect past human migrations in Southeast Asia.

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Breurec, Sebastien; Guillard, Bertrand; Hem, Sopheak; Brisse, Sylvain; Dieye, Fatou Bintou; Huerre, Michel; Oung, Chakravuth; Raymond, Josette; Tan, Tek Sreng; Thiberge, Jean-Michel; Vong, Sirenda; Monchy, Didier; Linz, Bodo

2011-01-01

The human population history in Southeast Asia was shaped by numerous migrations and population expansions. Their reconstruction based on archaeological, linguistic or human genetic data is often hampered by the limited number of informative polymorphisms in classical human genetic markers, such as the hypervariable regions of the mitochondrial DNA. Here, we analyse housekeeping gene sequences of the human stomach bacterium Helicobacter pylori from various countries in Southeast Asia and we provide evidence that H. pylori accompanied at least three ancient human migrations into this area: i) a migration from India introducing hpEurope bacteria into Thailand, Cambodia and Malaysia; ii) a migration of the ancestors of Austro-Asiatic speaking people into Vietnam and Cambodia carrying hspEAsia bacteria; and iii) a migration of the ancestors of the Thai people from Southern China into Thailand carrying H. pylori of population hpAsia2. Moreover, the H. pylori sequences reflect iv) the migrations of Chinese to Thailand and Malaysia within the last 200 years spreading hspEasia strains, and v) migrations of Indians to Malaysia within the last 200 years distributing both hpAsia2 and hpEurope bacteria. The distribution of the bacterial populations seems to strongly influence the incidence of gastric cancer as countries with predominantly hspEAsia isolates exhibit a high incidence of gastric cancer while the incidence is low in countries with a high proportion of hpAsia2 or hpEurope strains. In the future, the host range expansion of hpEurope strains among Asian populations, combined with human motility, may have a significant impact on gastric cancer incidence in Asia.

"While we are questioning we are progressing"—A Reply to the Ancestors of Qualitative Research

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Monika Götsch

2009-07-01

Full Text Available REICHERTZ' reflections on the development of qualitative research during the Berlin Meeting on Qualitative Research Methods in 2009 (http://www.berliner-methodentreffen.de/ have led to the following central questions: Are we facing the end of critical social research? Is this possible end correlated with an uncritical mass of young scientists? In their reply to the ancestors of qualitative research the present authors advocate the abolition of a bipolar thinking about the issues and support a hybrid turn, standing the test through a fundamentally open-minded, reflexive, and deconstructive researcher`s attitude. Using the example of ethnography and gender studies we show that there are indeed opportunities for the future of critical social research: This approach would take place beyond the slaves of market-controlled contract research and ahead of the characters of the eternal hall of fame of social research. URN: urn:nbn:de:0114-fqs0903306

The emergence of egalitarianism in a model of early human societies

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Guillaume Calmettes

2017-11-01

Full Text Available How did egalitarianism emerge in early human societies? In contrast to dominance hierarchies in non-human primates, human simple forager bands are typically egalitarian, with male hunters often serving as the collective alpha. Here we present a thermodynamics-inspired simple population model, based on stochastic optimization of dominance relationships, in which a dominance hierarchy of individuals with exclusively self-centered characteristics (the desire to dominate, resentment at being dominated transitions spontaneously to egalitarianism as their capacity for language develops. Language, specifically gossip, allows resentment against being dominated to promote the formation of antidominance coalitions which destabilize the alpha position for individuals, leading to a phase transition in which a coalition of the full population suddenly becomes dominant. Thus, egalitarianism emerges suddenly as the optimal power-sharing arrangement in a population of selfish individuals without any inherently altruistic qualities. We speculate that egalitarianism driven by punishment for exhibiting alpha-like behavior may then set the stage for genuinely altruistic traits to propagate as predicted by game theory models. Based on model simulations, we also predict that egalitarianism is a pre-condition for adaptation of tools as weapons. Potential implications for origins of human moral belief systems are discussed. Keywords: Sociology, Evolution, Anthropology

Comment: Characterization of Two Historic Smallpox Specimens from a Czech Museum.

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Porter, Ashleigh F; Duggan, Ana T; Poinar, Hendrik N; Holmes, Edward C

2017-09-28

The complete genome sequences of two strains of variola virus (VARV) sampled from human smallpox specimens present in the Czech National Museum, Prague, were recently determined, with one of the sequences estimated to date to the mid-19th century. Using molecular clock methods, the authors of this study go on to infer that the currently available strains of VARV share an older common ancestor, at around 1350 AD, than some recent estimates based on other archival human samples. Herein, we show that the two Czech strains exhibit anomalous branch lengths given their proposed age, and by assuming a constant rate of evolutionary change across the rest of the VARV phylogeny estimate that their true age in fact lies between 1918 and 1937. We therefore suggest that the age of the common ancestor of currently available VARV genomes most likely dates to late 16th and early 17th centuries and not ~1350 AD.

Comment: Characterization of Two Historic Smallpox Specimens from a Czech Museum

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Ashleigh F. Porter

2017-09-01

Full Text Available The complete genome sequences of two strains of variola virus (VARV sampled from human smallpox specimens present in the Czech National Museum, Prague, were recently determined, with one of the sequences estimated to date to the mid-19th century. Using molecular clock methods, the authors of this study go on to infer that the currently available strains of VARV share an older common ancestor, at around 1350 AD, than some recent estimates based on other archival human samples. Herein, we show that the two Czech strains exhibit anomalous branch lengths given their proposed age, and by assuming a constant rate of evolutionary change across the rest of the VARV phylogeny estimate that their true age in fact lies between 1918 and 1937. We therefore suggest that the age of the common ancestor of currently available VARV genomes most likely dates to late 16th and early 17th centuries and not ~1350 AD.

Early brain development toward shaping of human mind: an integrative psychoneurodevelopmental model in prenatal and perinatal medicine.

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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

Genomic structure of the native inhabitants of Peninsular Malaysia and North Borneo suggests complex human population history in Southeast Asia.

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Yew, Chee-Wei; Lu, Dongsheng; Deng, Lian; Wong, Lai-Ping; Ong, Rick Twee-Hee; Lu, Yan; Wang, Xiaoji; Yunus, Yushimah; Aghakhanian, Farhang; Mokhtar, Siti Shuhada; Hoque, Mohammad Zahirul; Voo, Christopher Lok-Yung; Abdul Rahman, Thuhairah; Bhak, Jong; Phipps, Maude E; Xu, Shuhua; Teo, Yik-Ying; Kumar, Subbiah Vijay; Hoh, Boon-Peng

2018-02-01

Southeast Asia (SEA) is enriched with a complex history of peopling. Malaysia, which is located at the crossroads of SEA, has been recognized as one of the hubs for early human migration. To unravel the genomic complexity of the native inhabitants of Malaysia, we sequenced 12 samples from 3 indigenous populations from Peninsular Malaysia and 4 native populations from North Borneo to a high coverage of 28-37×. We showed that the Negritos from Peninsular Malaysia shared a common ancestor with the East Asians, but exhibited some level of gene flow from South Asia, while the North Borneo populations exhibited closer genetic affinity towards East Asians than the Malays. The analysis of time of divergence suggested that ancestors of Negrito were the earliest settlers in the Malay Peninsula, whom first separated from the Papuans ~ 50-33 thousand years ago (kya), followed by East Asian (~ 40-15 kya), while the divergence time frame between North Borneo and East Asia populations predates the Austronesian expansion period implies a possible pre-Neolithic colonization. Substantial Neanderthal ancestry was confirmed in our genomes, as was observed in other East Asians. However, no significant difference was observed, in terms of the proportion of Denisovan gene flow into these native inhabitants from Malaysia. Judging from the similar amount of introgression in the Southeast Asians and East Asians, our findings suggest that the Denisovan gene flow may have occurred before the divergence of these populations and that the shared similarities are likely an ancestral component.

The evolution of air resonance power efficiency in the violin and its ancestors.

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Nia, Hadi T; Jain, Ankita D; Liu, Yuming; Alam, Mohammad-Reza; Barnas, Roman; Makris, Nicholas C

2015-03-08

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.

Two New Mylagaulid Rodents from the Early Miocene of China.

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Xiaoyu Lu

Full Text Available Mylagaulid fossorial rodents are a common component of North American Miocene fossil faunas. However outside of North America, only three species are known from Asia. Here we report two new mylagaulids, Irtyshogaulus minor gen. et sp. nov. and Irtyshogaulus major gen. et sp. nov., recovered from early Miocene sediments in the Junggar Basin in northwestern China. The two new taxa are small-sized, high-crowned promylagauline rodents. Their lower molars possess high metastylid crests, small mesostylids, broad and posterolingually expanded labial inflections, and transversely extending metalophid IIs. The mesoconid is absent in both species. The anterior and posterior fossettids are large and equally developed. Their upper M1-2s possess a square occlusal surface with five deep fossettes. The two new taxa are distinguished from each other mainly by their size, the morphology of fossettes and fossettids, development of mesial and distal lophs, posterior reduction of M3, and the orientation of m2 hypolophid. Our phylogenetic analysis indicates that Irtyshogaulus and Lamugaulus (another early Miocene Asian mylagaulid are sister taxa. The two genera are nested among the North American promylagaulines, and share a common ancestor from North America, indicating early Miocene intercontinental dispersal within this clade of rodents.

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

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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.

2015-01-01

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. PMID:25977457

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

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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.

Early-life experiences and the development of adult diseases with a focus on mental illness: The Human Birth Theory.

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Maccari, Stefania; Polese, Daniela; Reynaert, Marie-Line; Amici, Tiziana; Morley-Fletcher, Sara; Fagioli, Francesca

2017-02-07

In mammals, early adverse experiences, including mother-pup interactions, shape the response of an individual to chronic stress or to stress-related diseases during adult life. This has led to the elaboration of the theory of the developmental origins of health and disease, in particular adult diseases such as cardiovascular and metabolic disorders. In addition, in humans, as stated by Massimo Fagioli's Human Birth Theory, birth is healthy and equal for all individuals, so that mental illness develop exclusively in the postnatal period because of the quality of the relationship in the first year of life. Thus, this review focuses on the importance of programming during the early developmental period on the manifestation of adult diseases in both animal models and humans. Considering the obvious differences between animals and humans we cannot systematically move from animal models to humans. Consequently, in the first part of this review, we will discuss how animal models can be used to dissect the influence of adverse events occurring during the prenatal and postnatal periods on the developmental trajectories of the offspring, and in the second part, we will discuss the role of postnatal critical periods on the development of mental diseases in humans. Epigenetic mechanisms that cause reversible modifications in gene expression, driving the development of a pathological phenotype in response to a negative early postnatal environment, may lie at the core of this programming, thereby providing potential new therapeutic targets. The concept of the Human Birth Theory leads to a comprehension of the mental illness as a pathology of the human relationship immediately after birth and during the first year of life. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Noninvasive analysis of volatile biomarkers in human emanations for health and early disease diagnosis.

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Kataoka, Hiroyuki; Saito, Keita; Kato, Hisato; Masuda, Kazufumi

2013-06-01

Early disease diagnosis is crucial for human healthcare and successful therapy. Since any changes in homeostatic balance can alter human emanations, the components of breath exhalations and skin emissions may be diagnostic biomarkers for various diseases and metabolic disorders. Since hundreds of endogenous and exogenous volatile organic compounds (VOCs) are released from the human body, analysis of these VOCs may be a noninvasive, painless, and easy diagnostic tool. Sampling and preconcentration by sorbent tubes/traps and solid-phase microextraction, in combination with GC or GC-MS, are usually used to analyze VOCs. In addition, GC-MS-olfactometry is useful for simultaneous analysis of odorants and odor quality. Direct MS techniques are also useful for the online real-time detection of VOCs. This review focuses on recent developments in sampling and analysis of volatile biomarkers in human odors and/or emanations, and discusses future use of VOC analysis.

Open cup nests evolved from roofed nests in the early passerines.

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Price, J Jordan; Griffith, Simon C

2017-02-08

The architectural diversity of nests in the passerine birds (order Passeriformes) is thought to have played an important role in the adaptive radiation of this group, which now comprises more than half of avian species and occupies nearly all terrestrial ecosystems. Here, we present an extensive survey and ancestral state reconstruction of nest design across the passerines, focusing on early Australian lineages and including members of nearly all passerine families worldwide. Most passerines build open cup-shaped nests, whereas a minority build more elaborate domed structures with roofs. We provide strong evidence that, despite their relative rarity today, domed nests were constructed by the common ancestor of all modern passerines. Open cup nests evolved from enclosed domes at least four times independently during early passerine evolution, at least three of which occurred on the Australian continent, yielding several primarily cup-nesting clades that are now widespread and numerically dominant among passerines. Our results show that the ubiquitous and relatively simple cup-shaped nests of many birds today evolved multiple times convergently, suggesting adaptive benefits over earlier roofed designs. © 2017 The Author(s).

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

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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.

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

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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. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells*

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

2016-01-01

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

Molecular evolution of the endosperm starch synthesis pathway genes in rice (Oryza sativa L.) and its wild ancestor, O. rufipogon L.

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Yu, Guoqin; Olsen, Kenneth M; Schaal, Barbara A

2011-01-01

The evolution of metabolic pathways is a fundamental but poorly understood aspect of evolutionary change. One approach for understanding the complexity of pathway evolution is to examine the molecular evolution of genes that together comprise an integrated metabolic pathway. The rice endosperm starch biosynthetic pathway is one of the most thoroughly characterized metabolic pathways in plants, and starch is a trait that has evolved in response to strong selection during rice domestication. In this study, we have examined six key genes (AGPL2, AGPS2b, SSIIa, SBEIIb, GBSSI, ISA1) in the rice endosperm starch biosynthesis pathway to investigate the evolution of these genes before and after rice domestication. Genome-wide sequence tagged sites data were used as a neutral reference to overcome the problems of detecting selection in species with complex demographic histories such as rice. Five variety groups of Oryza sativa (aus, indica, tropical japonica, temperate japonica, aromatic) and its wild ancestor (O. rufipogon) were sampled. Our results showed evidence of purifying selection at AGPL2 in O. rufipogon and strong evidence of positive selection at GBSSI in temperate japonica and tropical japonica varieties and at GBSSI and SBEIIb in aromatic varieties. All the other genes showed a pattern consistent with neutral evolution in both cultivated rice and its wild ancestor. These results indicate the important role of positive selection in the evolution of starch genes during rice domestication. We discuss the role of SBEIIb and GBSSI in the evolution of starch quality during rice domestication and the power and limitation of detecting selection using genome-wide data as a neutral reference.

Tension in the Natural History of Human Thinking

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Moll Henrike

2016-03-01

Full Text Available Michael Tomasello has greatly expanded our knowledge of human cognition and how it differs from that of other animals. In this commentary to his recent book A Natural History of Human Thinking, I first critique some of the presuppositions and arguments of his evolutionary story about how homo sapiens’ cognition emerged. For example, I question the strategy of relying on the modern chimpanzee as a model for our last shared ancestor, and I doubt the idea that what changed first over evolutionary time was hominin behavior, which then in turn brought about changes in cognition. In the second half of the commentary I aim to show that the author oscillates between an additive and a transformative account of human shared intentionality. I argue that shared intentionality shapes cognition in its entirety and therefore precludes the possibility that humans have the same, individual intentionality (as shown in, e.g. their instrumental reasoning as other apes.

EVOLUTION. A four-legged snake from the Early Cretaceous of Gondwana.

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Martill, David M; Tischlinger, Helmut; Longrich, Nicholas R

2015-07-24

Snakes are a remarkably diverse and successful group today, but their evolutionary origins are obscure. The discovery of snakes with two legs has shed light on the transition from lizards to snakes, but no snake has been described with four limbs, and the ecology of early snakes is poorly known. We describe a four-limbed snake from the Early Cretaceous (Aptian) Crato Formation of Brazil. The snake has a serpentiform body plan with an elongate trunk, short tail, and large ventral scales suggesting characteristic serpentine locomotion, yet retains small prehensile limbs. Skull and body proportions as well as reduced neural spines indicate fossorial adaptation, suggesting that snakes evolved from burrowing rather than marine ancestors. Hooked teeth, an intramandibular joint, a flexible spine capable of constricting prey, and the presence of vertebrate remains in the guts indicate that this species preyed on vertebrates and that snakes made the transition to carnivory early in their history. The structure of the limbs suggests that they were adapted for grasping, either to seize prey or as claspers during mating. Together with a diverse fauna of basal snakes from the Cretaceous of South America, Africa, and India, this snake suggests that crown Serpentes originated in Gondwana. Copyright © 2015, American Association for the Advancement of Science.

Ectomycorrhizal fungi decompose soil organic matter using oxidative mechanisms adapted from saprotrophic ancestors.

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Shah, Firoz; Nicolás, César; Bentzer, Johan; Ellström, Magnus; Smits, Mark; Rineau, Francois; Canbäck, Björn; Floudas, Dimitrios; Carleer, Robert; Lackner, Gerald; Braesel, Jana; Hoffmeister, Dirk; Henrissat, Bernard; Ahrén, Dag; Johansson, Tomas; Hibbett, David S; Martin, Francis; Persson, Per; Tunlid, Anders

2016-03-01

Ectomycorrhizal fungi are thought to have a key role in mobilizing organic nitrogen that is trapped in soil organic matter (SOM). However, the extent to which ectomycorrhizal fungi decompose SOM and the mechanism by which they do so remain unclear, considering that they have lost many genes encoding lignocellulose-degrading enzymes that are present in their saprotrophic ancestors. Spectroscopic analyses and transcriptome profiling were used to examine the mechanisms by which five species of ectomycorrhizal fungi, representing at least four origins of symbiosis, decompose SOM extracted from forest soils. In the presence of glucose and when acquiring nitrogen, all species converted the organic matter in the SOM extract using oxidative mechanisms. The transcriptome expressed during oxidative decomposition has diverged over evolutionary time. Each species expressed a different set of transcripts encoding proteins associated with oxidation of lignocellulose by saprotrophic fungi. The decomposition 'toolbox' has diverged through differences in the regulation of orthologous genes, the formation of new genes by gene duplications, and the recruitment of genes from diverse but functionally similar enzyme families. The capacity to oxidize SOM appears to be common among ectomycorrhizal fungi. We propose that the ancestral decay mechanisms used primarily to obtain carbon have been adapted in symbiosis to scavenge nutrients instead. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

The politics of universalism. Strategic uses of human rights discourses in early modernity

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Karen-Margrethe Simonsen

2013-11-01

Full Text Available This article investigates the political function of human rights in 16th-century Spain just after the conquest of America. It claims that the study of this period of early globalization is relevant for an understanding of the function of human rights discourses today, at the “end” of globalization. Historically speaking, human rights are closely connected with globalization, but at the same time, they raise the question about the foundation of globalization: is there a universal community or only economic and political power-relations? This article argues that the political use of human rights discourses is split down the middle: it serves both as a critique of power and as an extension of power, and the disclosure of this split helps us understand the inner politics of human rights. The article discusses the trial in Valladolid in 1550 when the rights of the barbarian Indians of America were put on trial. It focuses mainly on the arguments made by Bartolomé de las Casas and on the reasons why the King allowed las Casas’ fierce critique of the conquest to be published in a period of otherwise severe censorship. This article is inspired by Etienne Balibar's idea of “politics of universalism,” “political autonomy,” and “equaliberty.”.

[Establishment of sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo].

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Jiang, Hua; Feng, You-Ji; Xie, Yi; Han, Jin-Lan; Wang, Zack; Chen, Tong

2008-10-14

To establish a sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo. Human embryonic stem were (hESCs) were cultured on the mouse embryo fibroblasts and then were induced to differentiate to form three-dimensional EB. The hEBs were cultured in media containing various angiogenesis-related factors: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), endostatin, angiostatin, and platelet factor (PF)-4 of different concentrations for 3 days to observe the sprouting of the hEBs. 3, 3, 3', 3'-tetramethylindo-carbocyanine perchlorate labeled acetylated low density lipoprotein (Dil-AcLDL) was added onto the hEBs foe 4 h Immunofluorescence assay was used to observe if Dil-AcLDL was absorbed and if CD31 was expressed so as to determine the existence of embryonic endothelial cells in the sprouting structures. The ideal culturing condition was analyzed. The differentiated EBs formed sprouting structures in the collagen I matrix containing VEGF and FGF. The sprouts among individual EBs were able to link to each other and form vascular network-like structures. In the presence of VEGF and FGF, the sprouts branching from the EBs assimilated Dil-AcLDL, expressed CD31 and formed a 3-dimensional cylindrical organization. The concentrations of growth factors ideally stimulating sprouting growth were 100 ng/ml of VEGF and 50 ng/ml of FGF. The networks among the EBs were abolished by the angiostatin, endostatin, and PF4. The sprouting from hEBs accumulates embryonic endothelial cells and the sprouting network-like structures are indeed endothelial in nature. Inducing of sprouting EBs is an ideal model that mimics early embryonic vasculogenesis in humans.

Photosynthetic microbial mats today, on early Earth, (and on early Mars?)

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Des Marais, D. J.

2008-05-01

Marine hypersaline cyanobacterial mats offer insights about their ancient ancestors, whose fossil record is 3.43 billion years old. Studies of mat microbiota have greatly expanded the known diversity of ancient microbial lineages. Their evolution was shaped by mat microenvironments, which can differ substantially from their surroundings. Oxygenic photosynthesis perhaps developed in microbial mats and probably triggered a major evolutionary transformation and diversification of the early biosphere. Gross primary production rates in cyanobacterial mats can rival the most productive ecosystems known. Sunlight changes in intensity and spectral composition as it penetrates mats, and counteracting gradients of O2 and sulfide shape the chemical microenvironment. A combination of benefits and hazards of light, O2 and sulfide promotes the allocation of the various essential mat processes between light and dark periods and to various depths in the mat. Close inspection has revealed surprises, for example: anoxygenic phototrophs inside cyanobacterial sheaths, record- high sulfate reduction rates in O2-saturated conditions, and high H2 fluxes into overlying waters. Diverse organic biomarker compounds have been documented that are amenable to long-term preservation. Such coordinated observations of populations, processes and products are making fundamental questions in ecology accessible. Cyanobacterial mats have robust fossil records in part because they populated stable continental platforms and margins, contributing to sediments having high preservation potential. Proterozoic cyanobacterial fossils and organic biomarkers are well documented. The 3.43 Ga Strelley Pool cherts, W. Australia, reveal diverse stromatolites that populated a partially restricted, low-energy shallow hypersaline basin. Molecular studies of extant bacteria hint that early chlorophyll-utilizing photosynthesizers required geochemical sources of reductants. Did these anoxygenic phototrophs once sustain an

A highly variable segment of human subterminal 16p reveals a history of population growth for modern humans outside Africa

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Alonso, Santos; Armour, John A. L.

2001-01-01

We have sequenced a highly polymorphic subterminal noncoding region from human chromosome 16p13.3, flanking the 5′ end of the hypervariable minisatellite MS205, in 100 chromosomes sampled from different African and Euroasiatic populations. Coalescence analysis indicates that the time to the most recent common ancestor (approximately 1 million years) predates the appearance of anatomically modern human forms. The root of the network describing this variability lies in Africa. African populations show a greater level of diversity and deeper branches. Most Euroasiatic variability seems to have been generated after a recent out-of-Africa range expansion. A history of population growth is the most likely scenario for the Euroasiatic populations. This pattern of nuclear variability can be reconciled with inferences based on mitochondrial DNA. PMID:11158547

Development and the evolvability of human limbs.

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Young, Nathan M; Wagner, Günter P; Hallgrímsson, Benedikt

2010-02-23

The long legs and short arms of humans are distinctive for a primate, the result of selection acting in opposite directions on each limb at different points in our evolutionary history. This mosaic pattern challenges our understanding of the relationship of development and evolvability because limbs are serially homologous and genetic correlations should act as a significant constraint on their independent evolution. Here we test a developmental model of limb covariation in anthropoid primates and demonstrate that both humans and apes exhibit significantly reduced integration between limbs when compared to quadrupedal monkeys. This result indicates that fossil hominins likely escaped constraints on independent limb variation via reductions to genetic pleiotropy in an ape-like last common ancestor (LCA). This critical change in integration among hominoids, which is reflected in macroevolutionary differences in the disparity between limb lengths, facilitated selection for modern human limb proportions and demonstrates how development helps shape evolutionary change.

Stem cell markers in the heart of the human newborn

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Armando Faa

2016-07-01

Full Text Available The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. Several recent studies now show that the different cell types that characterize the adult human heart arise from a common ancestor. Human cardiac stem cells differentiate into cardiomyocytes, and, in lesser extent, into smooth muscle and endothelial cells. The characterization of human cardiac stem cells (CSCs has important clinical implications. In recent years, CD117 (c-kit has been reported to mark a subtype of stem/progenitor cells in the human heart, with stem cell-like properties, including the ability to self-renewal and clonogenicity multipotentiality. Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

New thinking: the evolution of human cognition.

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Heyes, Cecilia

2012-08-05

Humans are animals that specialize in thinking and knowing, and our extraordinary cognitive abilities have transformed every aspect of our lives. In contrast to our chimpanzee cousins and Stone Age ancestors, we are complex political, economic, scientific and artistic creatures, living in a vast range of habitats, many of which are our own creation. Research on the evolution of human cognition asks what types of thinking make us such peculiar animals, and how they have been generated by evolutionary processes. New research in this field looks deeper into the evolutionary history of human cognition, and adopts a more multi-disciplinary approach than earlier 'Evolutionary Psychology'. It is informed by comparisons between humans and a range of primate and non-primate species, and integrates findings from anthropology, archaeology, economics, evolutionary biology, neuroscience, philosophy and psychology. Using these methods, recent research reveals profound commonalities, as well striking differences, between human and non-human minds, and suggests that the evolution of human cognition has been much more gradual and incremental than previously assumed. It accords crucial roles to cultural evolution, techno-social co-evolution and gene-culture co-evolution. These have produced domain-general developmental processes with extraordinary power-power that makes human cognition, and human lives, unique.

Early modern human dispersal from Africa: genomic evidence for multiple waves of migration.

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Tassi, Francesca; Ghirotto, Silvia; Mezzavilla, Massimo; Vilaça, Sibelle Torres; De Santi, Lisa; Barbujani, Guido

2015-01-01

Anthropological and genetic data agree in indicating the African continent as the main place of origin for anatomically modern humans. However, it is unclear whether early modern humans left Africa through a single, major process, dispersing simultaneously over Asia and Europe, or in two main waves, first through the Arab Peninsula into southern Asia and Oceania, and later through a northern route crossing the Levant. Here, we show that accurate genomic estimates of the divergence times between European and African populations are more recent than those between Australo-Melanesia and Africa and incompatible with the effects of a single dispersal. This difference cannot possibly be accounted for by the effects of either hybridization with archaic human forms in Australo-Melanesia or back migration from Europe into Africa. Furthermore, in several populations of Asia we found evidence for relatively recent genetic admixture events, which could have obscured the signatures of the earliest processes. We conclude that the hypothesis of a single major human dispersal from Africa appears hardly compatible with the observed historical and geographical patterns of genome diversity and that Australo-Melanesian populations seem still to retain a genomic signature of a more ancient divergence from Africa.

Indian Hedgehog in Synovial Fluid Is a Novel Marker for Early Cartilage Lesions in Human Knee Joint

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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 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

The origin and evolution of Homo sapiens.

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Stringer, Chris

2016-07-05

If we restrict the use of Homo sapiens in the fossil record to specimens which share a significant number of derived features in the skeleton with extant H. sapiens, the origin of our species would be placed in the African late middle Pleistocene, based on fossils such as Omo Kibish 1, Herto 1 and 2, and the Levantine material from Skhul and Qafzeh. However, genetic data suggest that we and our sister species Homo neanderthalensis shared a last common ancestor in the middle Pleistocene approximately 400-700 ka, which is at least 200 000 years earlier than the species origin indicated from the fossils already mentioned. Thus, it is likely that the African fossil record will document early members of the sapiens lineage showing only some of the derived features of late members of the lineage. On that basis, I argue that human fossils such as those from Jebel Irhoud, Florisbad, Eliye Springs and Omo Kibish 2 do represent early members of the species, but variation across the African later middle Pleistocene/early Middle Stone Age fossils shows that there was not a simple linear progression towards later sapiens morphology, and there was chronological overlap between different 'archaic' and 'modern' morphs. Even in the late Pleistocene within and outside Africa, we find H. sapiens specimens which are clearly outside the range of Holocene members of the species, showing the complexity of recent human evolution. The impact on species recognition of late Pleistocene gene flow between the lineages of modern humans, Neanderthals and Denisovans is also discussed, and finally, I reconsider the nature of the middle Pleistocene ancestor of these lineages, based on recent morphological and genetic data.This article is part of the themed issue 'Major transitions in human evolution'. © 2016 The Author(s).

Wild mallards have more "goose-like" bills than their ancestors: a case of anthropogenic influence?

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Pär Söderquist

Full Text Available 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.

Saffold virus, a human Theiler's-like cardiovirus, is ubiquitous and causes infection early in life.

Directory of Open Access Journals (Sweden)

Jan Zoll

2009-05-01

Full Text Available The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus. In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV and Theiler's murine encephalomyelits virus (TMEV. The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV. The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3 isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible

Ancient DNA reveals genetic connections between early Di-Qiang and Han Chinese.

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Li, Jiawei; Zeng, Wen; Zhang, Ye; Ko, Albert Min-Shan; Li, Chunxiang; Zhu, Hong; Fu, Qiaomei; Zhou, Hui

2017-12-04

Ancient Di-Qiang people once resided in the Ganqing region of China, adjacent to the Central Plain area from where Han Chinese originated. While gene flow between the Di-Qiang and Han Chinese has been proposed, there is no evidence to support this view. Here we analyzed the human remains from an early Di-Qiang site (Mogou site dated ~4000 years old) and compared them to other ancient DNA across China, including an early Han-related site (Hengbei site dated ~3000 years old) to establish the underlying genetic relationship between the Di-Qiang and ancestors of Han Chinese. We found Mogou mtDNA haplogroups were highly diverse, comprising 14 haplogroups: A, B, C, D (D*, D4, D5), F, G, M7, M8, M10, M13, M25, N*, N9a, and Z. In contrast, Mogou males were all Y-DNA haplogroup O3a2/P201; specifically one male was further assigned to O3a2c1a/M117 using targeted unique regions on the non-recombining region of the Y-chromosome. We compared Mogou to 7 other ancient and 38 modern Chinese groups, in a total of 1793 individuals, and found that Mogou shared close genetic distances with Taojiazhai (a more recent Di-Qiang population), Hengbei, and Northern Han. We modeled their interactions using Approximate Bayesian Computation, and support was given to a potential admixture of ~13-18% between the Mogou and Northern Han around 3300-3800 years ago. Mogou harbors the earliest genetically identifiable Di-Qiang, ancestral to the Taojiazhai, and up to ~33% paternal and ~70% of its maternal haplogroups could be found in present-day Northern Han Chinese.

Tolerance to early human milk feeding is not compromised by indomethacin in preterm infants with persistent ductus arteriosus.

Science.gov (United States)

Bellander, M; Ley, D; Polberger, S; Hellström-Westas, L

2003-09-01

Early human milk feeding is beneficial for gut and brain development. Persistent ductus arteriosus (PDA) and indomethacin may compromise enteral function in preterm infants. For many years enteral milk feedings have continued in preterm infants receiving indomethacin for PDA. The aim of this study was to investigate whether this strategy is efficient in terms of risks and tolerance to early enteral feeding. This retrospective study included 64 inborn infants of respiratory morbidity; 90.6% versus 50% of controls needed mechanical ventilation (p = 0.000). Case infants received human milk from a median (range) age of 4.0 h (1.5-27.5), and controls from 5.3 h (2.0-38.0) (p = 0.092). The first dose of indomethacin was given at a mean age of 1.7 d (1.0). There were no differences between the two groups in feeding volumes or gastric residuals on days 1 to 7. Mean (SD) feeding volume on day 7 was 64 ml/kg (31) in case infants and 76 ml/kg (30) in controls (p = 0.23). Four infants developed necrotizing enterocolitis: two case infants and two controls (p = 1.00). Early enteral feeding with human milk, starting within the first hours of life, seems to be as well tolerated in preterm infants treated with indomethacin for PDA as in their matched controls.

Human radiation studies: Remembering the early years: Oral history of pathologist Clarence Lushbaugh, M.D., conducted October 5, 1994

International Nuclear Information System (INIS)

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

Early evaluation of the effects of chemotherapy with longitudinal FDG small-animal PET in human testicular cancer xenografts: early flare response does not reflect refractory disease

Energy Technology Data Exchange (ETDEWEB)

Aide, Nicolas [GRECAN, EA 1772, IFR 146 ICORE, Caen University, Bioticla Unit, Caen (France); Francois Baclesse Comprehensive Cancer Centre, Nuclear Medicine Department, Caen (France); Centre Francois Baclesse, Service de Medecine Nucleaire, Caen Cedex 5 (France); Poulain, Laurent; Briand, Melanie; Dutoit, Soizic; Labiche, Alexandre; Gauduchon, Pascal [GRECAN, EA 1772, IFR 146 ICORE, Caen University, Bioticla Unit, Caen (France); Allouche, Stephane [University Hospital, Biochemistry Department, Caen (France); Ngo-Van Do, Aurelie; Nataf, Valerie; Talbot, Jean-Noel; Montravers, Francoise [Tenon Hospital and University Pierre et Marie Curie (Paris 6), LIMP, Paris (France); Batalla, Alain [Francois Baclesse Comprehensive Cancer Centre, Medical Physics Unit, Caen (France)

2009-03-15

We aimed to evaluate the usefulness of FDG PET in the early prediction of the effects of chemotherapy on human testicular cancer xenografts. Nude rats bearing subcutaneous human embryonal carcinoma xenografts received either cisplatin (5 mg/kg) or saline serum. Small-animal PET studies were performed on days 0, 2, 4 and 7 and compared to immunochemistry studies, flow cytometry studies and hexokinase assays. Cisplatin treatment resulted in biphasic FDG uptake evolution: a peak was observed on day 2, followed by a marked decrease on day 7 despite an insignificant change in tumour volume. Similarly, a peak in cyclin A immunostaining was observed on days 2 and 4, followed by a significant decrease on day 7. Flow cytometry showed that the cyclin A peak was not related to increased cell proliferation but was due to a transient S and G{sub 2}/M cell cycle arrest. A marked increase in cell apoptosis was observed from day 2 to day 7. GLUT-1 showed a significant decrease on day 7. Macrophagic infiltrate remained stable except for an increase observed on day 7. In control tumours, continuous growth was observed, all immunostaining markers remaining stable over time. Hexokinase activity was significantly lower on day 7 in treated tumours than in controls. FDG PET may be useful in the early evaluation of treatment in patients with testicular cancer. In our model, a very early increased [{sup 18}F]-FDG uptake was related to a transient cell cycle arrest and early stage apoptosis but did not reveal refractory disease. (orig.)

Dynamic locomotor capabilities revealed by early dinosaur trackmakers from southern Africa.

Directory of Open Access Journals (Sweden)

Jeffrey A Wilson

Full Text Available BACKGROUND: A new investigation of the sedimentology and ichnology of the Early Jurassic Moyeni tracksite in Lesotho, southern Africa has yielded new insights into the behavior and locomotor dynamics of early dinosaurs. METHODOLOGY/PRINCIPAL FINDINGS: The tracksite is an ancient point bar preserving a heterogeneous substrate of varied consistency and inclination that includes a ripple-marked riverbed, a bar slope, and a stable algal-matted bar top surface. Several basal ornithischian dinosaurs and a single theropod dinosaur crossed its surface within days or perhaps weeks of one another, but responded to substrate heterogeneity differently. Whereas the theropod trackmaker accommodated sloping and slippery surfaces by gripping the substrate with its pedal claws, the basal ornithischian trackmakers adjusted to the terrain by changing between quadrupedal and bipedal stance, wide and narrow gauge limb support (abduction range = 31 degrees , and plantigrade and digitigrade foot posture. CONCLUSIONS/SIGNIFICANCE: The locomotor adjustments coincide with changes in substrate consistency along the trackway and appear to reflect 'real time' responses to a complex terrain. It is proposed that these responses foreshadow important locomotor transformations characterizing the later evolution of the two main dinosaur lineages. Ornithischians, which shifted from bipedal to quadrupedal posture at least three times in their evolutionary history, are shown to have been capable of adopting both postures early in their evolutionary history. The substrate-gripping behavior demonstrated by the early theropod, in turn, is consistent with the hypothesized function of pedal claws in bird ancestors.

Genome digging: insight into the mitochondrial genome of Homo.

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Igor V Ovchinnikov

2010-12-01

Full Text Available A fraction of the Neanderthal mitochondrial genome sequence has a similarity with a 5,839-bp nuclear DNA sequence of mitochondrial origin (numt on the human chromosome 1. This fact has never been interpreted. Although this phenomenon may be attributed to contamination and mosaic assembly of Neanderthal mtDNA from short sequencing reads, we explain the mysterious similarity by integration of this numt (mtAncestor-1 into the nuclear genome of the common ancestor of Neanderthals and modern humans not long before their reproductive split.Exploiting bioinformatics, we uncovered an additional numt (mtAncestor-2 with a high similarity to the Neanderthal mtDNA and indicated that both numts represent almost identical replicas of the mtDNA sequences ancestral to the mitochondrial genomes of Neanderthals and modern humans. In the proteins, encoded by mtDNA, the majority of amino acids distinguishing chimpanzees from humans and Neanderthals were acquired by the ancestral hominins. The overall rate of nonsynonymous evolution in Neanderthal mitochondrial protein-coding genes is not higher than in other lineages. The model incorporating the ancestral hominin mtDNA sequences estimates the average divergence age of the mtDNAs of Neanderthals and modern humans to be 450,000-485,000 years. The mtAncestor-1 and mtAncestor-2 sequences were incorporated into the nuclear genome approximately 620,000 years and 2,885,000 years ago, respectively.This study provides the first insight into the evolution of the mitochondrial DNA in hominins ancestral to Neanderthals and humans. We hypothesize that mtAncestor-1 and mtAncestor-2 are likely to be molecular fossils of the mtDNAs of Homo heidelbergensis and a stem Homo lineage. The d(N/d(S dynamics suggests that the effective population size of extinct hominins was low. However, the hominin lineage ancestral to humans, Neanderthals and H. heidelbergensis, had a larger effective population size and possessed genetic diversity

Astronomical Theory of Early Human Migration (Milutin Milankovic Medal Lecture)

Science.gov (United States)

Timmermann, Axel; Friedrich, Tobias

2017-04-01

Our climate system varies on a wide range of timescales, from seasons to several millions of years. A large part of this variability is internally generated as a result of instabilities of the coupled atmosphere-ocean-ice-carbon cycle system. Other modes of variability, such as glacial cycles, are caused by astronomical forcings with periods of 20, 40, 100 thousand years. These so-called Milankovitch Cycles are associated with earth's axis wobble, axis obliquity and shifts in the eccentricity of earth's orbit around the sun, respectively. When these cycles conspire, they can cause the climate system to plunge into an ice-age. This happened last time 110,000 years ago, when Northern Hemisphere summer radiation decreased substantially and ice-sheets started to form as a result. Around 100,000 years ago northern Hemisphere summer moved again closer to the sun and Homo sapiens started to leave Africa across vegetated corridors in Northeastern Africa and the Arabian Peninsula. This first migration wave must have been relatively weak, but it left unequivocal traces in the fossil and archaeological record. Why Homo sapiens embarked on its grand journey across our planet during glacial climate conditions has been subject of an intense debate in various scientific communities. Moreover, the archaeological records of an early exodus around 100 thousand years ago seem to be at odds with paleo-genetic evidences, that place the first dispersal out of Africa around 70-60 thousand years ago. To elucidate what role climate and environmental conditions played in the dispersal of Anatomically Modern Humans out of Africa, we have developed and applied one of the first integrated climate/human migration computer models. The model simulates ice-ages, abrupt climate change, the "peopling" of our planet and captures the arrival time of Homo sapiens in the Levant, Arabian Peninsula, Southern China and Australia in close agreement with paleo climate reconstructions, fossil and

Gene expression analyses of the spatio-temporal relationships of human medulloblastoma subgroups during early human neurogenesis.

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Cornelia M Hooper

Full Text Available Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified - WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options. To address this issue, the gene expression profiles of normal human neural tissues and cell types representing a broad neuro-developmental continuum, were compared to those of two independent cohorts of primary human medulloblastoma specimens. Clustering, co-expression network, and gene expression analyses revealed that WNT and SHH medulloblastoma may be derived from distinct neural stem cell populations during early embryonic development, while the transcriptional profiles of Group 3 and Group 4 medulloblastoma resemble cerebellar granule neuron precursors at weeks 10-15 and 20-30 of embryogenesis, respectively. Our data indicate that Group 3 medulloblastoma may arise through abnormal neuronal differentiation, whereas deregulation of synaptic pruning-associated apoptosis may be driving Group 4 tumorigenesis. Overall, these data provide significant new insight into the spatio-temporal relationships and molecular pathogenesis of the human medulloblastoma subgroups, and provide an important framework for the development of more refined model systems, and ultimately improved therapeutic strategies.

Lower Cambrian biogeography and the prehistory of early animals

Energy Technology Data Exchange (ETDEWEB)

Signor, P.W. (Univ. of California, Davis (United States))

1991-02-01

Biogeographic distributions of animals reflect the complex interplay of biological and physical processes acting over geological time. In particular, plate tectonics and the evolution of lineages within clades play fundamental roles in determining faunal distributions. Ranges expand through vicariant events or dispersal and contract through local and regional extinctions. Vicariance promotes the evolutionary divergence of closely related lineages. Viewed as historical phenomena, biogeographic distributions can be employed to infer prior tectonic and evolutionary events. For example, the existence of modern marine faunal provinces reflects the interaction of evolution and plate tectonics. The Proterozoic history of skeletogenous organisms (and their ancestors) is a contentious subject, with many authors arguing that skeletogenous clades have no significant prehistory before their appearance in the fossil record. The existence of trilobite provinces dominated by different suborders, for example, suggests the trilobites evolved and dispersed, or were separated by plate movement, and then evolved independently for an extended period prior to their appearance in the fossil record. Similar arguments can be applied to other groups. The paleobiogeographic distribution of organisms also provides useful insights into late Proterozoic and Early Cambrian paleogeography. The provincial distribution of Early Cambrian taxa suggests that the putative Proterozoic supercontinent, if it existed, began to separate well before the Early Cambrian. Separate provinces would not have evolved had the various plates remained united. Therefore, the dawn of the Phanerozoic could not have coincided with the breakup of the Proterozoic supercontinent.

A complete human pelvis from the Middle Pleistocene of Spain.

Science.gov (United States)

Arsuaga, J L; Lorenzo, C; Carretero, J M; Gracia, A; Martínez, I; García, N; Bermúdez de Castro, J M; Carbonell, E

1999-05-20

The Middle Pleistocene site of Sima de los Huesos in Sierra de Atapuerca, Spain, has yielded around 2,500 fossils from at least 33 different hominid individuals. These have been dated at more than 200,000 years ago and have been classified as ancestors of Neanderthals. An almost complete human male pelvis (labelled Pelvis 1) has been found, which we associate with two fragmentary femora. Pelvis 1 is robust and very broad with a very long superior pubic ramus, marked iliac flare, and a long femoral neck. This pattern is probably the primitive condition from which modern humans departed. A modern human newborn would pass through the birth canal of Pelvis 1 and this would be even larger in a female individual. We estimate the body mass of this individual at 95 kg or more. Using the cranial capacities of three specimens from Sima de los Huesos, the encephalization quotients are substantially smaller than in Neanderthals and modern humans.

Specific interactions between transcription factors and the promoter-regulatory region of the human cytomegalovirus major immediate-early gene

International Nuclear Information System (INIS)

Ghazal, P.; Lubon, H.; Hennighausen, L.

1988-01-01

Repeat sequence motifs as well as unique sequences between nucleotides -150 and -22 of the human cytomegalovirus immediate-early 1 gene interact in vitro with nuclear proteins. The authors show that a transcriptional element between nucleotides -91 and -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

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

Science.gov (United States)

Anastasiou, Evilena; Mitchell, Piers D

2013-10-01

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

Culture and art: Importance of art practice, not aesthetics, to early human culture.

Science.gov (United States)

Zaidel, Dahlia W

2018-01-01

Art is expressed in multiple formats in today's human cultures. Physical traces of stone tools and other archaeological landmarks suggest early nonart cultural behavior and symbolic cognition in the early Homo sapiens (HS) who emerged ~300,000-200,000 years ago in Africa. Fundamental to art expression is the neural underpinning for symbolic cognition, and material art is considered its prime example. However, prior to producing material art, HS could have exploited symbolically through art-rooted biological neural pathways for social purpose, namely, those controlling interpersonal motoric coordination and sound codependence. Aesthetics would not have been the primary purpose; arguments for group dance and rhythmical musical sounds are offered here. In addition, triggers for symbolic body painting are discussed. These cultural art formats could well have preceded material art and would have enhanced unity, inclusiveness, and cooperative behavior, contributing significantly to already existing nonart cultural practices. © 2018 Elsevier B.V. All rights reserved.

Why did the First Farmers Toil?

DEFF Research Database (Denmark)

Weisdorf, Jacob Louis

Time-budget studies done among contemporary primitive people suggest that the first farmers worked harder to attain subsistence than their foraging predecessors. This makes the adoption of agriculture in the Stone Age one of the major curiosities in human cultural history. Theories offered...... by economists and economic historians largely fail to capture work-intensification among early farmers. Attributing a key role to human metabolism, this study provides a simple framework for analysing the adoption of agriculture. It demonstrates how the additional output that farming offered could have lured...... people into agriculture, but that subsequent population increase would eventually have swallowed up its benefits, forcing early farmers into an irreversible trap, where they had to do more work to attain subsistence compared to their foraging ancestors. The framework draws attention to the fact that...

Why did the First Farmers Toil?

DEFF Research Database (Denmark)

Weisdorf, Jacob Louis

2009-01-01

Time-budget studies done among contemporary primitive people suggest that the first farmers worked harder to attain subsistence than their foraging predecessors. This makes the adoption of agriculture in the Stone Age one of the major curiosities in human cultural history. Theories offered...... by economists and economic historians largely fail to capture work-intensification among early farmers. Attributing a key role to human metabolism, this study provides a simple framework for analysing the adoption of agriculture. It demonstrates how the additional output that farming offered could have lured...... people into agriculture, but that subsequent population increase would eventually have swallowed up its benefits, forcing early farmers into an irreversible trap, where they had to do more work to attain subsistence compared to their foraging ancestors. The framework draws attention to the fact that...

Characterization of the early local immune response to Ixodes ricinus tick bites in human skin.

Science.gov (United States)

Glatz, Martin; Means, Terry; Haas, Josef; Steere, Allen C; Müllegger, Robert R

2017-03-01

Little is known about the immunomodulation by tick saliva during a natural tick bite in human skin, the site of the tick-host interaction. We examined the expression of chemokines, cytokines and leucocyte markers on the mRNA levels and histopathologic changes in human skin biopsies of tick bites (n=37) compared to unaffected skin (n=9). Early tick-bite skin lesions (skin. With longer tick attachment (>24 hours), the numbers of innate immune cells and mediators (not significantly) declined, whereas the numbers of lymphocytes (not significantly) increased. Natural tick bites by Ixodes ricinus ticks initially elicit a strong local innate immune response in human skin. Beyond 24 hours of tick attachment, this response usually becomes less, perhaps because of immunomodulation by tick saliva. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Postcranial morphology of the middle Pleistocene humans from Sima de los Huesos, Spain.

Science.gov (United States)

Arsuaga, Juan Luis; Carretero, José-Miguel; Lorenzo, Carlos; Gómez-Olivencia, Asier; Pablos, Adrián; Rodríguez, Laura; García-González, Rebeca; Bonmatí, Alejandro; Quam, Rolf M; Pantoja-Pérez, Ana; Martínez, Ignacio; Aranburu, Arantza; Gracia-Téllez, Ana; Poza-Rey, Eva; Sala, Nohemi; García, Nuria; Alcázar de Velasco, Almudena; Cuenca-Bescós, Gloria; Bermúdez de Castro, José María; Carbonell, Eudald

2015-09-15

Current knowledge of the evolution of the postcranial skeleton in the genus Homo is hampered by a geographically and chronologically scattered fossil record. Here we present a complete characterization of the postcranium of the middle Pleistocene paleodeme from the Sima de los Huesos (SH) and its paleobiological implications. The SH hominins show the following: (i) wide bodies, a plesiomorphic character in the genus Homo inherited from their early hominin ancestors; (ii) statures that can be found in modern human middle-latitude populations that first appeared 1.6-1.5 Mya; and (iii) large femoral heads in some individuals, a trait that first appeared during the middle Pleistocene in Africa and Europe. The intrapopulational size variation in SH shows that the level of dimorphism was similar to modern humans (MH), but the SH hominins were less encephalized than Neandertals. SH shares many postcranial anatomical features with Neandertals. Although most of these features appear to be either plesiomorphic retentions or are of uncertain phylogenetic polarity, a few represent Neandertal apomorphies. Nevertheless, the full suite of Neandertal-derived features is not yet present in the SH population. The postcranial evidence is consistent with the hypothesis based on the cranial morphology that the SH hominins are a sister group to the later Neandertals. Comparison of the SH postcranial skeleton to other hominins suggests that the evolution of the postcranium occurred in a mosaic mode, both at a general and at a detailed level.

Early Pleistocene archaeological occurrences at the Feiliang site, and the archaeology of human origins in the Nihewan Basin, North China.

Directory of Open Access Journals (Sweden)

Shuwen Pei

Full Text Available The Early Pleistocene archaeological evidence from the fluvio-lacustrine sequence of the Nihewan Basin (North China offers an excellent opportunity to explore early human evolution and behavior in a temperate setting in East Asia, following the earliest 'Out of Africa'. Here we present the first comprehensive study of the Feiliang (FL site, with emphasis on the archaeological sequence, site integrity, and stone artifact assemblages. Magnetostratigraphic dating results show that early humans occupied the site ca. 1.2 Ma. Archaeological deposits were buried rapidly in primary context within shallow lake margin deposits, with only minor post-depositional disturbance from relatively low energy hydraulic forces. The FL lithic assemblage is characterized by a core and flake, Oldowan-like or Mode 1 technology, with a low degree of standardization, expedient knapping techniques, and casually retouched flakes. The bone assemblage suggests that hominin occupation of the FL site was in an open habitat of temperate grassland with areas of steppe and water. The main features of the FL assemblage are discussed in the context of the early Pleistocene archaeology of Nihewan, for which an assessment of current and future research is also presented.

Early evolution of the angiosperm clade Asteraceae in the Cretaceous of Antarctica.

Science.gov (United States)

Barreda, Viviana D; Palazzesi, Luis; Tellería, Maria C; Olivero, Eduardo B; Raine, J Ian; Forest, Félix

2015-09-01

The Asteraceae (sunflowers and daisies) are the most diverse family of flowering plants. Despite their prominent role in extant terrestrial ecosystems, the early evolutionary history of this family remains poorly understood. Here we report the discovery of a number of fossil pollen grains preserved in dinosaur-bearing deposits from the Late Cretaceous of Antarctica that drastically pushes back the timing of assumed origin of the family. Reliably dated to ∼76-66 Mya, these specimens are about 20 million years older than previously known records for the Asteraceae. Using a phylogenetic approach, we interpreted these fossil specimens as members of an extinct early diverging clade of the family, associated with subfamily Barnadesioideae. Based on a molecular phylogenetic tree calibrated using fossils, including the ones reported here, we estimated that the most recent common ancestor of the family lived at least 80 Mya in Gondwana, well before the thermal and biogeographical isolation of Antarctica. Most of the early diverging lineages of the family originated in a narrow time interval after the K/P boundary, 60-50 Mya, coinciding with a pronounced climatic warming during the Late Paleocene and Early Eocene, and the scene of a dramatic rise in flowering plant diversity. Our age estimates reduce earlier discrepancies between the age of the fossil record and previous molecular estimates for the origin of the family, bearing important implications in the evolution of flowering plants in general.

Fake news and post-truth pronouncements in general and in early human development.

Science.gov (United States)

Grech, Victor

2017-12-01

Fake news and post-truth pronouncements are increasingly common, and are unfortunately also progressively being applied to the sciences, including the medical sciences. This editorial briefly reviews this unsavoury trend and highlights recent debunking of fake truths in early human development. Science is arguably the last metanarrative with any significant cachet in the postmodern period. We, as scientists, must strive to ensure that our work is transparent and of the highest possible standard so as to continue to uphold science's integrity and probity. Copyright © 2017 Elsevier B.V. All rights reserved.

Auditory capacities in Middle Pleistocene humans from the Sierra de Atapuerca in Spain.

Science.gov (United States)

Martínez, I; Rosa, M; Arsuaga, J-L; Jarabo, P; Quam, R; Lorenzo, C; Gracia, A; Carretero, J-M; Bermúdez de Castro, J-M; Carbonell, E

2004-07-06

Human hearing differs from that of chimpanzees and most other anthropoids in maintaining a relatively high sensitivity from 2 kHz up to 4 kHz, a region that contains relevant acoustic information in spoken language. Knowledge of the auditory capacities in human fossil ancestors could greatly enhance the understanding of when this human pattern emerged during the course of our evolutionary history. Here we use a comprehensive physical model to analyze the influence of skeletal structures on the acoustic filtering of the outer and middle ears in five fossil human specimens from the Middle Pleistocene site of the Sima de los Huesos in the Sierra de Atapuerca of Spain. Our results show that the skeletal anatomy in these hominids is compatible with a human-like pattern of sound power transmission through the outer and middle ear at frequencies up to 5 kHz, suggesting that they already had auditory capacities similar to those of living humans in this frequency range.

Identification of Ohnolog Genes Originating from Whole Genome Duplication in Early Vertebrates, Based on Synteny Comparison across Multiple Genomes.

Science.gov (United States)

Singh, Param Priya; Arora, Jatin; Isambert, Hervé

2015-07-01

Whole genome duplications (WGD) have now been firmly established in all major eukaryotic kingdoms. In particular, all vertebrates descend from two rounds of WGDs, that occurred in their jawless ancestor some 500 MY ago. Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation. Ohnologs, which amount to about 20 to 35% of genes in the human genome, have also been shown to be prone to dominant deleterious mutations and frequently implicated in cancer and genetic diseases. Hence, identifying ohnologs is central to better understand the evolution of vertebrates and their susceptibility to genetic diseases. Early computational analyses to identify vertebrate ohnologs relied on content-based synteny comparisons between the human genome and a single invertebrate outgroup genome or within the human genome itself. These approaches are thus limited by lineage specific rearrangements in individual genomes. We report, in this study, the identification of vertebrate ohnologs based on the quantitative assessment and integration of synteny conservation between six amniote vertebrates and six invertebrate outgroups. Such a synteny comparison across multiple genomes is shown to enhance the statistical power of ohnolog identification in vertebrates compared to earlier approaches, by overcoming lineage specific genome rearrangements. Ohnolog gene families can be browsed and downloaded for three statistical confidence levels or recompiled for specific, user-defined, significance criteria at http://ohnologs.curie.fr/. In the light of the importance of WGD on the genetic makeup of vertebrates, our analysis provides a useful resource for researchers interested in gaining further insights on vertebrate evolution and genetic diseases.

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

Science.gov (United States)

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.

Randomized Controlled Trial on Effect of Intermittent Early Versus Late Kangaroo Mother Care on Human Milk Feeding in Low-Birth-Weight Neonates.

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Jayaraman, Dhaarani; Mukhopadhyay, Kanya; Bhalla, Anil Kumar; Dhaliwal, Lakhbir Kaur

2017-08-01

Breastfeeding at discharge among sick low-birth-weight (LBW) infants is low despite counseling and intervention like kangaroo mother care (KMC). Research aim: The aim was to study the effects of early initiation of KMC on exclusive human milk feeding, growth, mortality, and morbidities in LBW neonates compared with late initiation of KMC during the hospital stay and postdischarge. A randomized controlled trial was conducted in level 2 and 3 areas of a tertiary care neonatal unit over 15 months. Inborn neonates weighing 1 to 1.8 kg and hemodynamically stable were randomized to receive either early KMC, initiated within the first 4 days of life, or late KMC (off respiratory support and intravenous fluids). Follow-up was until 1 month postdischarge. Outcomes were proportion of infants achieving exclusive human milk feeding and direct breastfeeding, growth, mortality and morbidities during hospital stay, and postdischarge feeding and KMC practices until 1 month. The early KMC group ( n = 80) achieved significantly higher exclusive human milk feeding (86% vs. 45%, p milk feeding (73% vs. 36%, p milk feeding and direct breastfeeding in LBW infants.

A karyometric note on nucleoli in human early granulocytic precursors.

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Smetana, K; Mikulenková, D; Jirásková, I; Klamová, H

2006-01-01

The diameter of nucleoli was measured in human bone marrow early granulocytic precursors after visualization by a simple cytochemical method for demonstration of RNA. Such method facilitated to clearly see nucleolar bodies without perinucleolar chromatin, including those of micronucleoli. The bone marrow of patients suffering from chronic myeloid leukaemia (untreated with cytostatics) provided a satisfactory number of both myeloblasts and promyelocytes for nucleolar measurements because of prevailing granulopoiesis. The direct nucleolar measurement was carried out on digitized and processed images on the screen at magnification 4,300x. It seems to be likely that the nucleolar size is directly related to the number of nucleoli per cell. The largest nucleoli were present in both myeloblasts and promyelocytes that possessed a single nucleolus. In contrast, the nucleolar diameter was significantly smaller in cells with multiple nucleoli. However, in cells with small multiple nucleoli, one of them was always larger and dominant with a large number of AgNORs. Such large nucleoli are possibly visible in specimens stained with panoptic procedures or methods staining nuclear chromatin or DNA. It should also be mentioned that both myeloblasts and promyelocytes mostly possessed two nucleoli with the mean diameter close to 1.5 microm. The incidence of early granulocytic precursors classified according to the nucleolar number and size strongly suggested that the various nucleolar number and nucleolar size in these cells might be related to the different stage of the cell cycle and might also explain their heterogeneity.

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

Energy Technology Data Exchange (ETDEWEB)

Sherman, L.S.; Bennett, P.R.; Moore, G.E. [Queen Charlotte`s and Chelsea Hospital, London (United Kingdom)

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.

Early-life medical care and human capital accumulation

DEFF Research Database (Denmark)

Daysal, N. Meltem

2015-01-01

that both types of interventions may benefit not only child health but also long-term educational outcomes. In addition, early-life medical interventions may improve the educational outcomes of siblings. These findings can be used to design policies that improve long-term outcomes and reduce economic......Ample empirical evidence links adverse conditions during early childhood (the period from conception to age five) to worse health outcomes and lower academic achievement in adulthood. Can early-life medical care and public health interventions ameliorate these effects? Recent research suggests...

Human-climate interaction during the Early Upper Paleolithic: testing the hypothesis of an adaptive shift between the Proto-Aurignacian and the Early Aurignacian.

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Banks, William E; d'Errico, Francesco; Zilhão, João

2013-01-01

The Aurignacian technocomplex comprises a succession of culturally distinct phases. Between its first two subdivisions, the Proto-Aurignacian and the Early Aurignacian, we see a shift from single to separate reduction sequences for blade and bladelet production, the appearance of split-based antler points, and a number of other changes in stone tool typology and technology as well as in symbolic material culture. Bayesian modeling of available (14)C determinations, conducted within the framework of this study, indicates that these material culture changes are coincident with abrupt and marked climatic changes. The Proto-Aurignacian occurs during an interval (ca. 41.5-39.9 k cal BP) of relative climatic amelioration, Greenland Interstadials (GI) 10 and 9, punctuated by a short cold stadial. The Early Aurignacian (ca. 39.8-37.9 k cal BP) predominantly falls within the climatic phase known as Heinrich Stadial (HS) 4, and its end overlaps with the beginning of GI 8, the former being predominantly characterized by cold and dry conditions across the European continent. We use eco-cultural niche modeling to quantitatively evaluate whether these shifts in material culture are correlated with environmental variability and, if so, whether the ecological niches exploited by human populations shifted accordingly. We employ genetic algorithm (GARP) and maximum entropy (Maxent) techniques to estimate the ecological niches exploited by humans (i.e., eco-cultural niches) during these two phases of the Aurignacian. Partial receiver operating characteristic analyses are used to evaluate niche variability between the two phases. Results indicate that the changes in material culture between the Proto-Aurignacian and the Early Aurignacian are associated with an expansion of the ecological niche. These shifts in both the eco-cultural niche and material culture are interpreted to represent an adaptive response to the relative deterioration of environmental conditions at the onset of HS4

SARS-Coronavirus ancestor's foot-prints in South-East Asian bat colonies and the refuge theory.

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Gouilh, Meriadeg Ar; Puechmaille, Sébastien J; Gonzalez, Jean-Paul; Teeling, Emma; Kittayapong, Pattamaporn; Manuguerra, Jean-Claude

2011-10-01

One of the great challenges in the ecology of infectious diseases is to understand what drives the emergence of new pathogens including the relationship between viruses and their hosts. In the case of the emergence of SevereAcute Respiratory Syndrome Coronavirus (SARS-CoV), several studies have shown coronavirus diversity in bats as well as the existence of SARS-CoV infection in apparently healthy bats, suggesting that bats may be a crucial host in the genesis of this disease. To elucidate the biogeographic origin of SARS-CoV and investigate the role that bats played in its emergence, we amplified coronavirus sequences from bat species captured throughout Thailand and assessed the phylogenetic relationships to each other and to other published coronavirus sequences. To this end, RdRp sequence of Coronavirinae was targeted by RT-PCR in non-invasive samples from bats collected in Thailand. Two new coronaviruses were detected in two bat species: one Betacoronavirus in Hipposideros larvatus and one Alphacoronavirus in Hipposiderosarmiger. Interestingly, these viruses from South-East Asia are related to those previously detected in Africa (Betacoronavirus-b) or in Europe (Alphacoronavirus & Betacoronavirus-b). These findings illuminate the origin and the evolutionary history of the SARS-CoV group found in bats by pushing forward the hypothesis of a Betacoronavirus spill-over from Hipposideridae to Rhinolophidae and then from Rhinolophidae to civets and Human. All reported Betacoronaviruses-b (SARS-CoV group) of Hipposideridae and Rhinolophidae respectively cluster in two groups despite their broad geographic distribution and the sympatry of their hosts, which is in favor of an ancient and genetically independent evolution of Betacoronavirus-b clusters in these families. Moreover, despite its probable pathogenicity, we found that a Betacoronavirus-b can persistently infect a medium-sized hipposiderid bat colony. These findings illustrate the importance of the host

The human gut and groundwater harbor non-photosynthetic bacteria belonging to a new candidate phylum sibling to Cyanobacteria

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Di Rienzi, Sara C; Sharon, Itai; Wrighton, Kelly C; Koren, Omry; Hug, Laura A; Thomas, Brian C; Goodrich, Julia K; Bell, Jordana T; Spector, Timothy D; Banfield, Jillian F; Ley, Ruth E

2013-01-01

Cyanobacteria were responsible for the oxygenation of the ancient atmosphere; however, the evolution of this phylum is enigmatic, as relatives have not been characterized. Here we use whole genome reconstruction of human fecal and subsurface aquifer metagenomic samples to obtain complete genomes for members of a new candidate phylum sibling to Cyanobacteria, for which we propose the designation ‘Melainabacteria’. Metabolic analysis suggests that the ancestors to both lineages were non-photosynthetic, anaerobic, motile, and obligately fermentative. Cyanobacterial light sensing may have been facilitated by regulators present in the ancestor of these lineages. The subsurface organism has the capacity for nitrogen fixation using a nitrogenase distinct from that in Cyanobacteria, suggesting nitrogen fixation evolved separately in the two lineages. We hypothesize that Cyanobacteria split from Melainabacteria prior or due to the acquisition of oxygenic photosynthesis. Melainabacteria remained in anoxic zones and differentiated by niche adaptation, including for symbiosis in the mammalian gut. DOI: http://dx.doi.org/10.7554/eLife.01102.001 PMID:24137540

Early childhood development: impact of national human development, family poverty, parenting practices and access to early childhood education.

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Tran, T D; Luchters, S; Fisher, J

2017-05-01

This study was to describe and quantify the relationships among family poverty, parents' caregiving practices, access to education and the development of children living in low- and middle-income countries (LAMIC). We conducted a secondary analysis of data collected in UNICEF's Multiple Indicator Cluster Surveys (MICS). Early childhood development was assessed in four domains: language-cognitive, physical, socio-emotional and approaches to learning. Countries were classified into three groups on the basis of the Human Development Index (HDI). Overall, data from 97 731 children aged 36 to 59 months from 35 LAMIC were included in the after analyses. The mean child development scale score was 4.93 out of a maximum score of 10 (95%CI 4.90 to 4.97) in low-HDI countries and 7.08 (95%CI 7.05 to 7.12) in high-HDI countries. Family poverty was associated with lower child development scores in all countries. The total indirect effect of family poverty on child development score via attending early childhood education, care for the child at home and use of harsh punishments at home was -0.13 SD (77.8% of the total effect) in low-HDI countries, -0.09 SD (23.8% of the total effect) in medium-HDI countries and -0.02 SD (6.9% of the total effect) in high-HDI countries. Children in the most disadvantaged position in their societies and children living in low-HDI countries are at the greatest risk of failing to reach their developmental potential. Optimizing care for child development at home is essential to reduce the adverse effects of poverty on children's early development and subsequent life. © 2016 John Wiley & Sons Ltd.

Evolution, human-microbe interactions, and life history plasticity.

Science.gov (United States)

Rook, Graham; Bäckhed, Fredrik; Levin, Bruce R; McFall-Ngai, Margaret J; McLean, Angela R

2017-07-29

A bacterium was once a component of the ancestor of all eukaryotic cells, and much of the human genome originated in microorganisms. Today, all vertebrates harbour large communities of microorganisms (microbiota), particularly in the gut, and at least 20% of the small molecules in human blood are products of the microbiota. Changing human lifestyles and medical practices are disturbing the content and diversity of the microbiota, while simultaneously reducing our exposures to the so-called old infections and to organisms from the natural environment with which human beings co-evolved. Meanwhile, population growth is increasing the exposure of human beings to novel pathogens, particularly the crowd infections that were not part of our evolutionary history. Thus some microbes have co-evolved with human beings and play crucial roles in our physiology and metabolism, whereas others are entirely intrusive. Human metabolism is therefore a tug-of-war between managing beneficial microbes, excluding detrimental ones, and channelling as much energy as is available into other essential functions (eg, growth, maintenance, reproduction). This tug-of-war shapes the passage of each individual through life history decision nodes (eg, how fast to grow, when to mature, and how long to live). Copyright © 2017 Elsevier Ltd. All rights reserved.

Establishing the volatile profile of pig carcasses as analogues for human decomposition during the early postmortem period

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P. Armstrong

2016-02-01

Full Text Available Following a mass disaster, it is important that victims are rapidly located as the chances of survival decrease greatly after approximately 48 h. Urban search and rescue (USAR teams may use a range of tools to assist their efforts but detector dogs still remain one of the most effective search tools to locate victims of mass disasters. USAR teams can choose to deploy human scent dogs (trained to locate living victims or human remains detection (HRD dogs (trained to locate deceased victims. However, little is known about the variation between live human scent and postmortem human remains scent and the timeframe during which one type of scent transitions to the other. The aim of the current study was to measure the change in the scent profile of human decomposition analogues during the first 72 h postmortem by measuring the volatile organic compounds (VOCs that comprise the odour. Three pig carcasses (Sus scrofa domesticus L. were placed on a soil surface and allowed to decompose under natural conditions. Decomposition odour was sampled frequently up to 75 h postmortem and analysed using comprehensive two-dimensional gas chromatography – time-of-flight mass spectrometry (GC×GC-TOFMS. A total of 105 postmortem VOCs were identified during the early postmortem period. The VOC profile during the early postmortem period was highly dynamic, changing both hourly and daily. A transition period was observed after 43 h postmortem, where the VOC profile appeared to shift from a distinct antemortem odour to a more generalised postmortem odour. These findings are important in informing USAR teams and their use of detector dogs for disaster victim recovery.

Indian Hedgehog in Synovial Fluid Is a Novel Marker for Early Cartilage Lesions in Human Knee Joint

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Congming Zhang

2014-04-01

Full Text Available 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.

Emergence and Adaptation of a Novel Highly Pathogenic H7N9 Influenza Virus in Birds and Humans from a 2013 Human-Infecting Low-Pathogenic Ancestor.

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Qi, Wenbao; Jia, Weixin; Liu, Di; Li, Jing; Bi, Yuhai; Xie, Shumin; Li, Bo; Hu, Tao; Du, Yingying; Xing, Li; Zhang, Jiahao; Zhang, Fuchun; Wei, Xiaoman; Eden, John-Sebastian; Li, Huanan; Tian, Huaiyu; Li, Wei; Su, Guanming; Lao, Guangjie; Xu, Chenggang; Xu, Bing; Liu, Wenjun; Zhang, Guihong; Ren, Tao; Holmes, Edward C; Cui, Jie; Shi, Weifeng; Gao, George F; Liao, Ming

2018-01-15

Since its emergence in 2013, the H7N9 low-pathogenic avian influenza virus (LPAIV) has been circulating in domestic poultry in China, causing five waves of human infections. A novel H7N9 highly pathogenic avian influenza virus (HPAIV) variant possessing multiple basic amino acids at the cleavage site of the hemagglutinin (HA) protein was first reported in two cases of human infection in January 2017. More seriously, those novel H7N9 HPAIV variants have been transmitted and caused outbreaks on poultry farms in eight provinces in China. Herein, we demonstrate the presence of three different amino acid motifs at the cleavage sites of these HPAIV variants which were isolated from chickens and humans and likely evolved from the preexisting LPAIVs. Animal experiments showed that these novel H7N9 HPAIV variants are both highly pathogenic in chickens and lethal to mice. Notably, human-origin viruses were more pathogenic in mice than avian viruses, and the mutations in the PB2 gene associated with adaptation to mammals (E627K, A588V, and D701N) were identified by next-generation sequencing (NGS) and Sanger sequencing of the isolates from infected mice. No polymorphisms in the key amino acid substitutions of PB2 and HA in isolates from infected chicken lungs were detected by NGS. In sum, these results highlight the high degree of pathogenicity and the valid transmissibility of this new H7N9 variant in chickens and the quick adaptation of this new H7N9 variant to mammals, so the risk should be evaluated and more attention should be paid to this variant. IMPORTANCE Due to the recent increased numbers of zoonotic infections in poultry and persistent human infections in China, influenza A(H7N9) virus has remained a public health threat. Most of the influenza A(H7N9) viruses reported previously have been of low pathogenicity. Now, these novel H7N9 HPAIV variants have caused human infections in three provinces and outbreaks on poultry farms in eight provinces in China. We analyzed

The origin and early evolution of dinosaurs.

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Langer, Max C; Ezcurra, Martin D; Bittencourt, Jonathas S; Novas, Fernando E

2010-02-01

The oldest unequivocal records of Dinosauria were unearthed from Late Triassic rocks (approximately 230 Ma) accumulated over extensional rift basins in southwestern Pangea. The better known of these are Herrerasaurus ischigualastensis, Pisanosaurus mertii, Eoraptor lunensis, and Panphagia protos from the Ischigualasto Formation, Argentina, and Staurikosaurus pricei and Saturnalia tupiniquim from the Santa Maria Formation, Brazil. No uncontroversial dinosaur body fossils are known from older strata, but the Middle Triassic origin of the lineage may be inferred from both the footprint record and its sister-group relation to Ladinian basal dinosauromorphs. These include the typical Marasuchus lilloensis, more basal forms such as Lagerpeton and Dromomeron, as well as silesaurids: a possibly monophyletic group composed of Mid-Late Triassic forms that may represent immediate sister taxa to dinosaurs. The first phylogenetic definition to fit the current understanding of Dinosauria as a node-based taxon solely composed of mutually exclusive Saurischia and Ornithischia was given as "all descendants of the most recent common ancestor of birds and Triceratops". Recent cladistic analyses of early dinosaurs agree that Pisanosaurus mertii is a basal ornithischian; that Herrerasaurus ischigualastensis and Staurikosaurus pricei belong in a monophyletic Herrerasauridae; that herrerasaurids, Eoraptor lunensis, and Guaibasaurus candelariensis are saurischians; that Saurischia includes two main groups, Sauropodomorpha and Theropoda; and that Saturnalia tupiniquim is a basal member of the sauropodomorph lineage. On the contrary, several aspects of basal dinosaur phylogeny remain controversial, including the position of herrerasaurids, E. lunensis, and G. candelariensis as basal theropods or basal saurischians, and the affinity and/or validity of more fragmentary taxa such as Agnosphitys cromhallensis, Alwalkeria maleriensis, Chindesaurus bryansmalli, Saltopus elginensis, and

Early Gene Expression in Wounded Human Keratinocytes Revealed by DNA Microarray Analysis

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Pascal Barbry

2006-04-01

Full Text Available Wound healing involves several steps: spreading of the cells, migration and proliferation. We have profiled gene expression during the early events of wound healing in normal human keratinocytes with a home-made DNA microarray containing about 1000 relevant human probes. An original wounding machine was used, that allows the wounding of up to 40% of the surface of a confluent monolayer of cultured cells grown on a Petri dish (compared with 5% with a classical ‘scratch’ method. The two aims of the present study were: (a to validate a limited number of genes by comparing the expression levels obtained with this technique with those found in the literature; (b to combine the use of the wounding machine with DNA microarray analysis for large-scale detection of the molecular events triggered during the early stages of the wound-healing process. The time-courses of RNA expression observed at 0.5, 1.5, 3, 6 and 15 h after wounding for genes such as c-Fos, c-Jun, Egr1, the plasminogen activator PLAU (uPA and the signal transducer and transcription activator STAT3, were consistent with previously published data. This suggests that our methodologies are able to perform quantitative measurement of gene expression. Transcripts encoding two zinc finger proteins, ZFP36 and ZNF161, and the tumour necrosis factor α-induced protein TNFAIP3, were also overexpressed after wounding. The role of the p38 mitogen-activated protein kinase (p38MAPK in wound healing was shown after the inhibition of p38 by SB203580, but our results also suggest the existence of surrogate activating pathways.

Origin of Bacteriochlorophyll a and the Early Diversification of Photosynthesis.

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Tanai Cardona

Full Text Available Photosynthesis originated in the domain Bacteria billions of years ago; however, the identity of the last common ancestor to all phototrophic bacteria remains undetermined and speculative. Here I present the evolution of BchF or 3-vinyl-bacteriochlorophyll hydratase, an enzyme exclusively found in bacteria capable of synthetizing bacteriochlorophyll a. I show that BchF exists in two forms originating from an early divergence, one found in the phylum Chlorobi, including its paralogue BchV, and a second form that was ancestral to the enzyme found in the remaining anoxygenic phototrophic bacteria. The phylogeny of BchF is consistent with bacteriochlorophyll a evolving in an ancestral phototrophic bacterium that lived before the radiation event that gave rise to the phylum Chloroflexi, Chlorobi, Acidobacteria, Proteobacteria, and Gemmatimonadetes, but only after the divergence of Type I and Type II reaction centers. Consequently, it is suggested that the lack of phototrophy in many groups of extant bacteria is a derived trait.

Tuberin and PRAS40 are anti-apoptotic gatekeepers during early human amniotic fluid stem-cell differentiation.

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Fuchs, Christiane; Rosner, Margit; Dolznig, Helmut; Mikula, Mario; Kramer, Nina; Hengstschläger, Markus

2012-03-01

Embryoid bodies (EBs) are three-dimensional multicellular aggregates allowing the in vitro investigation of stem-cell differentiation processes mimicking early embryogenesis. Human amniotic fluid stem (AFS) cells harbor high proliferation potential, do not raise the ethical issues of embryonic stem cells, have a lower risk for tumor development, do not need exogenic induction of pluripotency and are chromosomal stable. Starting from a single human AFS cell, EBs can be formed accompanied by the differentiation into cells of all three embryonic germ layers. Here, we report that siRNA-mediated knockdown of the endogenous tuberous sclerosis complex-2 (TSC2) gene product tuberin or of proline-rich Akt substrate of 40 kDa (PRAS40), the two major negative regulators of mammalian target of rapamycin (mTOR), leads to massive apoptotic cell death during EB development of human AFS cells without affecting the endodermal, mesodermal and ectodermal cell differentiation spectrum. Co-knockdown of endogenous mTOR demonstrated these effects to be mTOR-dependent. Our findings prove this enzyme cascade to be an essential anti-apoptotic gatekeeper of stem-cell differentiation during EB formation. These data allow new insights into the regulation of early stem-cell maintenance and differentiation and identify a new role of the tumor suppressor tuberin and the oncogenic protein PRAS40 with the relevance for a more detailed understanding of the pathogenesis of diseases associated with altered activities of these gene products.

Investing in Early Human Development: Timing and Economic Efficiency

Science.gov (United States)

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

2010-01-01

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. PMID:19213617

Identification of a contemporary human parechovirus type 1 by VIDISCA and characterisation of its full genome

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Drexler Jan

2008-02-01

Full Text Available Abstract Background Enteritis is caused by a spectrum of viruses that is most likely not fully characterised. When testing stool samples by cell culture, virus isolates are sometimes obtained which cannot be typed by current methods. In this study we used VIDISCA, a virus identification method which has not yet been widely applied, on such an untyped virus isolate. Results We found a human parechovirus (HPeV type 1 (strain designation: BNI-788st. Because genomes of contemporary HPeV1 were not available, we determined its complete genome sequence. We found that the novel strain was likely the result of recombination between structural protein genes of an ancestor of contemporary HPeV1 strains and nonstructural protein genes from an unknown ancestor, most closely related to HPeV3. In contrast to the non-structural protein genes of other HPeV prototype strains, the non-structural protein genes of BNI-788st and HPeV3 prototype strains did not co-segregate in bootscan analysis with that of other prototype strains. Conclusion HPeV3 nonstructural protein genes may form a distinct element in a pool of circulating HPeV non-structural protein genes. More research into the complex HPeV evolution is required to connect virus ecology with disease patterns in humans.

The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons.

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Braasch, Ingo; Gehrke, Andrew R; Smith, Jeramiah J; Kawasaki, Kazuhiko; Manousaki, Tereza; Pasquier, Jeremy; Amores, Angel; Desvignes, Thomas; Batzel, Peter; Catchen, Julian; Berlin, Aaron M; Campbell, Michael S; Barrell, Daniel; Martin, Kyle J; Mulley, John F; Ravi, Vydianathan; Lee, Alison P; Nakamura, Tetsuya; Chalopin, Domitille; Fan, Shaohua; Wcisel, Dustin; Cañestro, Cristian; Sydes, Jason; Beaudry, Felix E G; Sun, Yi; Hertel, Jana; Beam, Michael J; Fasold, Mario; Ishiyama, Mikio; Johnson, Jeremy; Kehr, Steffi; Lara, Marcia; Letaw, John H; Litman, Gary W; Litman, Ronda T; Mikami, Masato; Ota, Tatsuya; Saha, Nil Ratan; Williams, Louise; Stadler, Peter F; Wang, Han; Taylor, John S; Fontenot, Quenton; Ferrara, Allyse; Searle, Stephen M J; Aken, Bronwen; Yandell, Mark; Schneider, Igor; Yoder, Jeffrey A; Volff, Jean-Nicolas; Meyer, Axel; Amemiya, Chris T; Venkatesh, Byrappa; Holland, Peter W H; Guiguen, Yann; Bobe, Julien; Shubin, Neil H; Di Palma, Federica; Alföldi, Jessica; Lindblad-Toh, Kerstin; Postlethwait, John H

2016-04-01

To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.

First trimester pregnancy-associated plasma protein A and human chorionic gonadotropin-beta in early and late pre-eclampsia

DEFF Research Database (Denmark)

Karahasanovic, Azra; Sørensen, Steen; Nilas, Lisbeth

2014-01-01

Abstract Background: The aim of this study was to compare pregnancy-associated plasma protein A (PAPP-A) and the β-subunit of human chorionic gonadotropin (hCGβ) measured in maternal plasma at the first trimester screening, in women who later developed early or late pre-eclampsia (PE) to women...... with normal pregnancies. Methods: In the study were included 161 cases with PE and 88 controls with uncomplicated pregnancies. Plasma PAPP-A and hCGβ were measured between gestational age (GA) 8+2 and 14+0, and cases with early and late onset PE were compared with controls. Results: Median of hCGβ (Mo...

On the nature and evolution of the neural bases of human language

Science.gov (United States)

Lieberman, Philip

2002-01-01

the brains of human beings and other species provides insight into the evolution of the brain bases of human language. The neural substrate that regulated motor control in the common ancestor of apes and humans most likely was modified to enhance cognitive and linguistic ability. Speech communication played a central role in this process. However, the process that ultimately resulted in the human brain may have started when our earliest hominid ancestors began to walk.

Early experience with human papillomavirus vaccine introduction in the United States, Canada and Australia.

Science.gov (United States)

Shefer, Abigail; Markowitz, Lauri; Deeks, Shelley; Tam, Theresa; Irwin, Kathleen; Garland, Suzanne M; Schuchat, Anne

2008-08-19

Successful incorporation of a new vaccine into a nation's vaccination program requires addressing a number of issues, including: 1) establishing national recommendations; 2) assuring education of and acceptance by the public and medical community; 3) establishing and maintaining an appropriate infrastructure for vaccine delivery; 4) financing the vaccine and the program, in addition to political will. This article reviews the early experience with implementation of human papillomavirus (HPV) vaccination programs. It focuses on the United States of America and Canada and provides a brief report on Australia, where introduction is underway.

CSF levels of hypocretin-1 (orexin-A) peak during early infancy in humans.

Science.gov (United States)

Aran, Adi; Shors, Irina; Lin, Ling; Mignot, Emmanuel; Schimmel, Michael S

2012-02-01

Hypocretin (orexin) is a unique neuropeptide involved in the consolidation of wakefulness and sleep. Although hypocretin-1 levels in the cerebrospinal fluid (CSF) are stable after infancy, how levels change in preterm and term human infants is unknown. Hypocretin-1 levels were measured in CSF samples, obtained from 284 preterm (25-37 gestational weeks) and full-term infants in the first 4 months of life and 35 older children (ages 0.5-13 years), in a tertiary hospital. Detailed clinical and laboratory data were collected for each of the 319 participants. Based on that data, 108 neurologically intact children were selected (95 infants [43 preterm and 52 term] and 13 older children). CSF hypocretin-1 was measured by direct radioimmunoassay. Hypocretin-1 levels at the first weeks of the 3rd embryonic trimester (gestational age [GA] 28-34 weeks) were 314 ± 65 pg/mL (n = 17). The levels linearly increased during the third trimester and early infancy (r = 0.6), peaking in infants of 2-4 months ages (476 ± 72 pg/mL; n = 16) and decreasing thereafter; hypocretin levels in 2- to 4-month-old infants were significantly higher than those in children 0.5-13 years old (353 ± 78 pg/mL, n = 13; P = 0.0001). The present findings indicate that in human infants, CSF hypocretin-1 increases during the third embryonic trimester and is highest at 4 months of life. Thereafter, and consistent with previously published results, hypocretin levels are lower and stable until the geriatric age. This pattern may reflect the role of hypocretin in the dramatic process of sleep and wakefulness consolidation that occurs during early infancy.

Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

Science.gov (United States)

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

Lecture One: Rediscovering Darwin for theology – Rethinking human personhood

Directory of Open Access Journals (Sweden)

J. Wentzel van Huyssteen

2017-11-01

Full Text Available In a series of three articles, presented at the Goshen Annual Conference on Science and Religion in 2015, with the theme ‘Interdisciplinary Theology and the Archeology of Personhood’, J. Wentzel van Huyssteen considers the problem of human evolution – also referred to as ‘the archaeology of personhood’ – and its broader impact on theological anthropology. These Goshen Lectures explore the potentiality that the history of human evolution provides bridge theories to theological anthropology and thus to a positive and constructive way of appropriating Darwinian thought for a public, interdisciplinary Christian theology. Lecture One tracks a select number of contemporary proposals for the evolution of aspects of human personhood. These aspects were of significance for Darwin: the evolution of cognition; the evolution of imagination, music and language; the evolution of morality; and the evolution of the religious disposition. The article acknowledges the close ties to hominid ancestors and focuses on the emergence of human distinctiveness, consciousness and personhood, and the propensity for religious awareness and experience.

Application of Carnegie stages of development to unify human and baboon ultrasound findings early in pregnancy.

Science.gov (United States)

Santolaya-Forgas, Joaquin; De Leon-Luis, Juan; Friel, Lara A; Wolf, Roman

2007-09-01

The objective of this study was to determine if very early ultrasonographic measurements obtained from human and baboon are comparable. For this purpose, the gestational, amniotic and yolk sacs, embryonic crown rump length (CRL) and heart rate were measured ultrasonographically between 35 and 47 days from the mean day of a three-day mating period in baboons (n=18) and between 42 to 58 days from fertilization as calculated from the CRL measurements in human pregnancies (n=82). Ultrasonographic measurements from both species were then plotted in the same graph using Carnegie stages of embryonic development as the independent variable to allow for visual comparisons. Mean gestational age at ultrasonographic studies was significantly different for humans and baboons (50.4 vs. 41 days, respectively; p>0.01). Significant correlations (p>0.01) were noted between ultrasonographic measurements and Carnegie stages of development in both humans and baboons. Only the gestational and the yolk sacs were significantly smaller in baboons than in humans (p>0.05). The findings that embryonic CRL, extra-embryonic space and heart rate are very similar between the 17th and 23rd Carnegie developmental stages make the baboon a promising surrogate of human pregnancy for investigations using celocentesis.

Re-evaluating the Glacial Vegetation of the Southern Levant and Early Signs of Human Impact on the Environment

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Miebach, A.; Chen, C.; Litt, T.

2017-12-01

Assessing paleoenvironmental conditions is crucial to understand the history of modern humans. The southern Levant functioned as a corridor for human migration processes such as the colonization of Europe and the spread of agriculture. Despite its important role in human history, the Levantine paleoenvironment is still insufficiently investigated. In particular, current reconstructions of the paleovegetation are grounded on poor data bases. Here, we revise former hypotheses about the paleovegetation of the southern Levant during the last glacial based on new palynological results from the Sea of Galilee and the Dead Sea. We further evaluate early signs of anthropogenic influences in the Dead Sea catchment by combining evidence of pollen, micro-charcoal, and spores. The palynological results suggest that drought-adapted herbs, dwarf shrubs, and grasses prevailed in the southern Levant during the last glacial. In contrast to the Holocene, there was no belt of continuous and dense Mediterranean vegetation surrounding the Sea of Galilee during MIS 2. Mediterranean elements such as deciduous oaks only occurred in limited amounts and were probably patchily distributed in the whole study area. The vegetation and moisture gradient was not as strong as today. Since the Lateglacial, the Dead Sea region witnessed several rapid environmental changes. Phases with considerably reduced woodland density, increased fire activity, and enhanced catchment erosion occurred. Although climatic triggers were possible, there is a strong indication of anthropogenic influences due to overall increasing human activities in the region. The study gains new insights into environmental responses of the southern Levant to climate variations in the past. It also contributes towards our understanding of human-environmental interactions during the early Holocene.

Spectroscopic imaging of the pilocarpine model of human epilepsy suggests that early NAA reduction predicts epilepsy.

Science.gov (United States)

Gomes, W A; Lado, F A; de Lanerolle, N C; Takahashi, K; Pan, C; Hetherington, H P

2007-08-01

Reduced hippocampal N-acetyl aspartate (NAA) is commonly observed in patients with advanced, chronic temporal lobe epilepsy (TLE). It is unclear, however, whether an NAA deficit is also present during the clinically quiescent latent period that characterizes early TLE. This question has important implications for the use of MR spectroscopic imaging (MRSI) in the early identification of patients at risk for TLE. To determine whether NAA is diminished during the latent period, we obtained high-resolution (1)H spectroscopic imaging during the latent period of the rat pilocarpine model of human TLE. We used actively detuneable surface reception and volume transmission coils to enhance sensitivity and a semiautomated voxel shifting method to accurately position voxels within the hippocampi. During the latent period, 2 and 7 d following pilocarpine treatment, hippocampal NAA was significantly reduced by 27.5 +/- 6.9% (P NAA deficit is not due to neuron loss and therefore likely represents metabolic impairment of hippocampal neurons during the latent phase. Therefore, spectroscopic imaging provides an early marker for metabolic dysfunction in this model of TLE.

Early Human Occupation on the Northeast Tibetan Plateau

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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

The spotted gar genome illuminates vertebrate evolution and facilitates human-to-teleost comparisons

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Braasch, Ingo; Gehrke, Andrew R.; Smith, Jeramiah J.; Kawasaki, Kazuhiko; Manousaki, Tereza; Pasquier, Jeremy; Amores, Angel; Desvignes, Thomas; Batzel, Peter; Catchen, Julian; Berlin, Aaron M.; Campbell, Michael S.; Barrell, Daniel; Martin, Kyle J.; Mulley, John F.; Ravi, Vydianathan; Lee, Alison P.; Nakamura, Tetsuya; Chalopin, Domitille; Fan, Shaohua; Wcisel, Dustin; Cañestro, Cristian; Sydes, Jason; Beaudry, Felix E. G.; Sun, Yi; Hertel, Jana; Beam, Michael J.; Fasold, Mario; Ishiyama, Mikio; Johnson, Jeremy; Kehr, Steffi; Lara, Marcia; Letaw, John H.; Litman, Gary W.; Litman, Ronda T.; Mikami, Masato; Ota, Tatsuya; Saha, Nil Ratan; Williams, Louise; Stadler, Peter F.; Wang, Han; Taylor, John S.; Fontenot, Quenton; Ferrara, Allyse; Searle, Stephen M. J.; Aken, Bronwen; Yandell, Mark; Schneider, Igor; Yoder, Jeffrey A.; Volff, Jean-Nicolas; Meyer, Axel; Amemiya, Chris T.; Venkatesh, Byrappa; Holland, Peter W. H.; Guiguen, Yann; Bobe, Julien; Shubin, Neil H.; Di Palma, Federica; Alföldi, Jessica; Lindblad-Toh, Kerstin; Postlethwait, John H.

2016-01-01

To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before the teleost genome duplication (TGD). The slowly evolving gar genome conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization, and development (e.g., Hox, ParaHox, and miRNA genes). Numerous conserved non-coding elements (CNEs, often cis-regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles of such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses revealed that the sum of expression domains and levels from duplicated teleost genes often approximate patterns and levels of gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes, and the function of human regulatory sequences. PMID:26950095

Resting State Functional Connectivity in Early Blind Humans

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Harold eBurton

2014-04-01

Full Text Available 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.

Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds

International Nuclear Information System (INIS)

Josse, Rozenn; Dumont, Julie; Fautrel, Alain; Robin, Marie-Anne; Guillouzo, André

2012-01-01

Gene expression profiling has recently emerged as a promising approach to identify early target genes and discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens. However, early gene changes induced by genotoxic compounds in human liver remain largely unknown. Primary human hepatocytes and differentiated HepaRG cells were exposed to aflatoxin B1 (AFB1) that induces DNA damage following enzyme-mediated bioactivation. Gene expression profile changes induced by a 24 h exposure of these hepatocyte models to 0.05 and 0.25 μM AFB1 were analyzed by using oligonucleotide pangenomic microarrays. The main altered signaling pathway was the p53 pathway and related functions such as cell cycle, apoptosis and DNA repair. Direct involvement of the p53 protein in response to AFB1 was verified by using siRNA directed against p53. Among the 83 well-annotated genes commonly modulated in two pools of three human hepatocyte populations and HepaRG cells, several genes were identified as altered by AFB1 for the first time. In addition, a subset of 10 AFB1-altered genes, selected upon basis of their function or tumor suppressor role, was tested in four human hepatocyte populations and in response to other chemicals. Although they exhibited large variable inter-donor fold-changes, several of these genes, particularly FHIT, BCAS3 and SMYD3, were found to be altered by various direct and other indirect genotoxic compounds and unaffected by non-genotoxic compounds. Overall, this comprehensive analysis of early gene expression changes induced by AFB1 in human hepatocytes identified a gene subset that included several genes representing potential biomarkers of genotoxic compounds. -- Highlights: ► Gene expression profile changes induced by aflatoxin B1 in human hepatocytes. ► AFB1 modulates various genes including tumor suppressor genes and proto-oncogenes. ► Important inter-individual variations in the response to AFB1. ► Some genes also altered by other

Terrestrial origin of viviparity in mesozoic marine reptiles indicated by early triassic embryonic fossils.

Science.gov (United States)

Motani, Ryosuke; Jiang, Da-yong; Tintori, Andrea; Rieppel, Olivier; Chen, Guan-bao

2014-01-01

Viviparity in Mesozoic marine reptiles has traditionally been considered an aquatic adaptation. We report a new fossil specimen that strongly contradicts this traditional interpretation. The new specimen contains the oldest fossil embryos of Mesozoic marine reptile that are about 10 million years older than previous such records. The fossil belongs to Chaohusaurus (Reptilia, Ichthyopterygia), which is the oldest of Mesozoic marine reptiles (ca. 248 million years ago, Early Triassic). This exceptional specimen captures an articulated embryo in birth position, with its skull just emerged from the maternal pelvis. Its headfirst birth posture, which is unlikely to be a breech condition, strongly indicates a terrestrial origin of viviparity, in contrast to the traditional view. The tail-first birth posture in derived ichthyopterygians, convergent with the conditions in whales and sea cows, therefore is a secondary feature. The unequivocally marine origin of viviparity is so far not known among amniotes, a subset of vertebrate animals comprising mammals and reptiles, including birds. Therefore, obligate marine amniotes appear to have evolved almost exclusively from viviparous land ancestors. Viviparous land reptiles most likely appeared much earlier than currently thought, at least as early as the recovery phase from the end-Permian mass extinction.

Forces shaping the fastest evolving regions in the human genome.

Directory of Open Access Journals (Sweden)

Katherine S Pollard

2006-10-01

Full Text Available Comparative genomics allow us to search the human genome for segments that were extensively changed in the last approximately 5 million years since divergence from our common ancestor with chimpanzee, but are highly conserved in other species and thus are likely to be functional. We found 202 genomic elements that are highly conserved in vertebrates but show evidence of significantly accelerated substitution rates in human. These are mostly in non-coding DNA, often near genes associated with transcription and DNA binding. Resequencing confirmed that the five most accelerated elements are dramatically changed in human but not in other primates, with seven times more substitutions in human than in chimp. The accelerated elements, and in particular the top five, show a strong bias for adenine and thymine to guanine and cytosine nucleotide changes and are disproportionately located in high recombination and high guanine and cytosine content environments near telomeres, suggesting either biased gene conversion or isochore selection. In addition, there is some evidence of directional selection in the regions containing the two most accelerated regions. A combination of evolutionary forces has contributed to accelerated evolution of the fastest evolving elements in the human genome.

Toward the Darwinian transition: Switching between distributed and speciated states in a simple model of early life.

Science.gov (United States)

Arnoldt, Hinrich; Strogatz, Steven H; Timme, Marc

2015-01-01

It has been hypothesized that in the era just before the last universal common ancestor emerged, life on earth was fundamentally collective. Ancient life forms shared their genetic material freely through massive horizontal gene transfer (HGT). At a certain point, however, life made a transition to the modern era of individuality and vertical descent. Here we present a minimal model for stochastic processes potentially contributing to this hypothesized "Darwinian transition." The model suggests that HGT-dominated dynamics may have been intermittently interrupted by selection-driven processes during which genotypes became fitter and decreased their inclination toward HGT. Stochastic switching in the population dynamics with three-point (hypernetwork) interactions may have destabilized the HGT-dominated collective state and essentially contributed to the emergence of vertical descent and the first well-defined species in early evolution. A systematic nonlinear analysis of the stochastic model dynamics covering key features of evolutionary processes (such as selection, mutation, drift and HGT) supports this view. Our findings thus suggest a viable direction out of early collective evolution, potentially enabling the start of individuality and vertical Darwinian evolution.

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

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

NONE

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.

Treatment with human immunoglobulin G improves the early disease course in a mouse model of Duchenne muscular dystrophy.

Science.gov (United States)

Zschüntzsch, Jana; Zhang, Yaxin; Klinker, Florian; Makosch, Gregor; Klinge, Lars; Malzahn, Dörthe; Brinkmeier, Heinrich; Liebetanz, David; Schmidt, Jens

2016-01-01

Duchenne muscular dystrophy (DMD) is a severe hereditary myopathy. Standard treatment by glucocorticosteroids is limited because of numerous side effects. The aim of this study was to test immunomodulation by human immunoglobulin G (IgG) as treatment in the experimental mouse model (mdx) of DMD. 2 g/kg human IgG compared to human albumin was injected intraperitoneally in mdx mice at the age of 3 and 7 weeks. Advanced voluntary wheel running parameters were recorded continuously. At the age of 11 weeks, animals were killed so that blood, diaphragm, and lower limb muscles could be removed for quantitative PCR, histological analysis and ex vivo muscle contraction tests. IgG compared to albumin significantly improved the voluntary running performance and reduced muscle fatigability in an ex vivo muscle contraction test. Upon IgG treatment, serum creatine kinase values were diminished and mRNA expression levels of relevant inflammatory markers were reduced in the diaphragm and limb muscles. Macrophage infiltration and myopathic damage were significantly ameliorated in the quadriceps muscle. Collectively, this study demonstrates that, in the early disease course of mdx mice, human IgG improves the running performance and diminishes myopathic damage and inflammation in the muscle. Therefore, IgG may be a promising approach for treatment of DMD. Two monthly intraperitoneal injections of human immunoglobulin G (IgG) improved the early 11-week disease phase of mdx mice. Voluntary running was improved and serum levels of creatine kinase were diminished. In the skeletal muscle, myopathic damage was ameliorated and key inflammatory markers such as mRNA expression of SPP1 and infiltration by macrophages were reduced. The study suggests that IgG could be explored as a potential treatment option for Duchenne muscular dystrophy and that pre-clinical long-term studies should be helpful. © 2015 International Society for Neurochemistry.

Heatwave Early Warning Systems and Adaptation Advice to Reduce Human Health Consequences of Heatwaves

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Bertil Forsberg

2011-12-01

Full Text Available 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.

International Human Rights to Early Intervention for Infants and Young Children with Disabilities: Tools for Global Advocacy

Science.gov (United States)

Brown, Sharan E.; Guralnick, Michael J.

2015-01-01

With almost universal ratification of the Convention on the Rights of the Child and the growing number of States Parties that have signed or ratified the Convention on the Rights of Persons with Disabilities, the majority of countries in the world have now committed to implementing the human rights articulated in these treaties. In this article we first provide an overview of both Conventions, highlight the articles in the treaties that are relevant to early intervention for infants and young children with disabilities, and describe the specific duties required of States Parties to ensure compliance including international cooperation. Second, a series of early intervention action principles are put forward that can help States Parties translate the underlying values of the Conventions into practice. PMID:26213446

Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis

Science.gov (United States)

Bos, Kirsten I.; Harkins, Kelly M.; Herbig, Alexander; Coscolla, Mireia; Weber, Nico; Comas, Iñaki; Forrest, Stephen A.; Bryant, Josephine M.; Harris, Simon R.; Schuenemann, Verena J.; Campbell, Tessa J.; Majander, Kerrtu; Wilbur, Alicia K.; Guichon, Ricardo A.; Wolfe Steadman, Dawnie L.; Cook, Della Collins; Niemann, Stefan; Behr, Marcel A.; Zumarraga, Martin; Bastida, Ricardo; Huson, Daniel; Nieselt, Kay; Young, Douglas; Parkhill, Julian; Buikstra, Jane E.; Gagneux, Sebastien; Stone, Anne C.; Krause, Johannes

2015-01-01

Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact1. This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World2. Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch3, although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-old mycobacterial genomes from Peruvian human skeletons, revealing that a member of the M. tuberculosis complex caused human disease before contact. The ancient strains are distinct from known human-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean. PMID:25141181

IL-2 Enhances Gut Homing Potential of Human Naive Regulatory T Cells Early in Life.

Science.gov (United States)

Hsu, Peter S; Lai, Catherine L; Hu, Mingjing; Santner-Nanan, Brigitte; Dahlstrom, Jane E; Lee, Cheng Hiang; Ajmal, Ayesha; Bullman, Amanda; Arbuckle, Susan; Al Saedi, Ahmed; Gacis, Lou; Nambiar, Reta; Williams, Andrew; Wong, Melanie; Campbell, Dianne E; Nanan, Ralph

2018-06-15

Recent evidence suggests early environmental factors are important for gut immune tolerance. Although the role of regulatory T (Treg) cells for gut immune homeostasis is well established, the development and tissue homing characteristics of Treg cells in children have not been studied in detail. In this article, we studied the development and homing characteristics of human peripheral blood Treg cell subsets and potential mechanisms inducing homing molecule expression in healthy children. We found contrasting patterns of circulating Treg cell gut and skin tropism, with abundant β7 integrin + Treg cells at birth and increasing cutaneous lymphocyte Ag (CLA + ) Treg cells later in life. β7 integrin + Treg cells were predominantly naive, suggesting acquisition of Treg cell gut tropism early in development. In vitro, IL-7 enhanced gut homing but reduced skin homing molecule expression in conventional T cells, whereas IL-2 induced a similar effect only in Treg cells. This effect was more pronounced in cord compared with adult blood. Our results suggest that early in life, naive Treg cells may be driven for gut tropism by their increased sensitivity to IL-2-induced β7 integrin upregulation, implicating a potential role of IL-2 in gut immune tolerance during this critical period of development. Copyright © 2018 by The American Association of Immunologists, Inc.

The Complete Chloroplast Genome of a Key Ancestor of Modern Roses, Rosa chinensis var. spontanea, and a Comparison with Congeneric Species

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Hong-Ying Jian

2018-02-01

Full Text Available Rosa chinensis var. spontanea, an endemic and endangered plant of China, is one of the key ancestors of modern roses and a source for famous traditional Chinese medicines against female diseases, such as irregular menses and dysmenorrhea. In this study, the complete chloroplast (cp genome of R. chinensis var. spontanea was sequenced, analyzed, and compared to congeneric species. The cp genome of R. chinensis var. spontanea is a typical quadripartite circular molecule of 156,590 bp in length, including one large single copy (LSC region of 85,910 bp and one small single copy (SSC region of 18,762 bp, separated by two inverted repeat (IR regions of 25,959 bp. The GC content of the whole genome is 37.2%, while that of LSC, SSC, and IR is 42.8%, 35.2% and 31.2%, respectively. The genome encodes 129 genes, including 84 protein-coding genes (PCGs, 37 transfer RNA (tRNA genes, and eight ribosomal RNA (rRNA genes. Seventeen genes in the IR regions were found to be duplicated. Thirty-three forward and five inverted repeats were detected in the cp genome of R. chinensis var. spontanea. The genome is rich in SSRs. In total, 85 SSRs were detected. A genome comparison revealed that IR contraction might be the reason for the relatively smaller cp genome size of R. chinensis var. spontanea compared to other congeneric species. Sequence analysis revealed that the LSC and SSC regions were more divergent than the IR regions within the genus Rosa and that a higher divergence occurred in non-coding regions than in coding regions. A phylogenetic analysis showed that the sampled species of the genus Rosa formed a monophyletic clade and that R. chinensis var. spontanea shared a more recent ancestor with R. lichiangensis of the section Synstylae than with R. odorata var. gigantea of the section Chinenses. This information will be useful for the conservation genetics of R. chinensis var. spontanea and for the phylogenetic study of the genus Rosa, and it might also

The Complete Chloroplast Genome of a Key Ancestor of Modern Roses, Rosa chinensis var. spontanea, and a Comparison with Congeneric Species.

Science.gov (United States)

Jian, Hong-Ying; Zhang, Yong-Hong; Yan, Hui-Jun; Qiu, Xian-Qin; Wang, Qi-Gang; Li, Shu-Bin; Zhang, Shu-Dong

2018-02-12

Rosa chinensis var. spontanea , an endemic and endangered plant of China, is one of the key ancestors of modern roses and a source for famous traditional Chinese medicines against female diseases, such as irregular menses and dysmenorrhea. In this study, the complete chloroplast (cp) genome of R. chinensis var. spontanea was sequenced, analyzed, and compared to congeneric species. The cp genome of R. chinensis var. spontanea is a typical quadripartite circular molecule of 156,590 bp in length, including one large single copy (LSC) region of 85,910 bp and one small single copy (SSC) region of 18,762 bp, separated by two inverted repeat (IR) regions of 25,959 bp. The GC content of the whole genome is 37.2%, while that of LSC, SSC, and IR is 42.8%, 35.2% and 31.2%, respectively. The genome encodes 129 genes, including 84 protein-coding genes (PCGs), 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. Seventeen genes in the IR regions were found to be duplicated. Thirty-three forward and five inverted repeats were detected in the cp genome of R. chinensis var. spontanea. The genome is rich in SSRs. In total, 85 SSRs were detected. A genome comparison revealed that IR contraction might be the reason for the relatively smaller cp genome size of R. chinensis var. spontanea compared to other congeneric species. Sequence analysis revealed that the LSC and SSC regions were more divergent than the IR regions within the genus Rosa and that a higher divergence occurred in non-coding regions than in coding regions. A phylogenetic analysis showed that the sampled species of the genus Rosa formed a monophyletic clade and that R. chinensis var. s pontanea shared a more recent ancestor with R. lichiangensis of the section Synstylae than with R. odorata var. gigantea of the section Chinenses . This information will be useful for the conservation genetics of R. chinensis var. spontanea and for the phylogenetic study of the genus Rosa , and it might also facilitate the

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

Science.gov (United States)

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. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Utility of a human FcRn transgenic mouse model in drug discovery for early assessment and prediction of human pharmacokinetics of monoclonal antibodies

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Avery, Lindsay B.; Wang, Mengmeng; Kavosi, Mania S.; Joyce, Alison; Kurz, Jeffrey C.; Fan, Yao-Yun; Dowty, Martin E.; Zhang, Minlei; Zhang, Yiqun; Cheng, Aili; Hua, Fei; Jones, Hannah M.; Neubert, Hendrik; Polzer, Robert J.; O'Hara, Denise M.

2016-01-01

ABSTRACT Therapeutic antibodies continue to develop as an emerging drug class, with a need for preclinical tools to better predict in vivo characteristics. Transgenic mice expressing human neonatal Fc receptor (hFcRn) have potential as a preclinical pharmacokinetic (PK) model to project human PK of monoclonal antibodies (mAbs). Using a panel of 27 mAbs with a broad PK range, we sought to characterize and establish utility of this preclinical animal model and provide guidance for its application in drug development of mAbs. This set of mAbs was administered to both hemizygous and homozygous hFcRn transgenic mice (Tg32) at a single intravenous dose, and PK parameters were derived. Higher hFcRn protein tissue expression was confirmed by liquid chromatography-high resolution tandem mass spectrometry in Tg32 homozygous versus hemizygous mice. Clearance (CL) was calculated using non-compartmental analysis and correlations were assessed to historical data in wild-type mouse, non-human primate (NHP), and human. Results show that mAb CL in hFcRn Tg32 homozygous mouse correlate with human (r2 = 0.83, r = 0.91, p PK studies, enhancement of the early selection of lead molecules, and ultimately a decrease in the time for a drug candidate to reach the clinic. PMID:27232760

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

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Rhys J.P. Skelton

2014-07-01

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

Top-down modulation of human early visual cortex after stimulus offset supports successful postcued report.

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Sergent, Claire; Ruff, Christian C; Barbot, Antoine; Driver, Jon; Rees, Geraint

2011-08-01

Modulations of sensory processing in early visual areas are thought to play an important role in conscious perception. To date, most empirical studies focused on effects occurring before or during visual presentation. By contrast, several emerging theories postulate that sensory processing and conscious visual perception may also crucially depend on late top-down influences, potentially arising after a visual display. To provide a direct test of this, we performed an fMRI study using a postcued report procedure. The ability to report a target at a specific spatial location in a visual display can be enhanced behaviorally by symbolic auditory postcues presented shortly after that display. Here we showed that such auditory postcues can enhance target-specific signals in early human visual cortex (V1 and V2). For postcues presented 200 msec after stimulus termination, this target-specific enhancement in visual cortex was specifically associated with correct conscious report. The strength of this modulation predicted individual levels of performance in behavior. By contrast, although later postcues presented 1000 msec after stimulus termination had some impact on activity in early visual cortex, this modulation no longer related to conscious report. These results demonstrate that within a critical time window of a few hundred milliseconds after a visual stimulus has disappeared, successful conscious report of that stimulus still relates to the strength of top-down modulation in early visual cortex. We suggest that, within this critical time window, sensory representation of a visual stimulus is still under construction and so can still be flexibly influenced by top-down modulatory processes.

Revalidation of the genus Chiloguembelitria Hofker: Implications for the evolution of early Danian planktonic foraminifera

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Arenillas, Ignacio; Arz, José A.; Gilabert, Vicente

2017-10-01

Guembelitria is the only planktonic foraminiferal genus whose survival from the mass extinction event of the Cretaceous/Paleogene (K/Pg) boundary has been clearly proven. The evolution of Guembelitria after the K/Pg boundary led to the appearance of two guembelitriid lineages in the early Danian: one biserial, represented by Woodringina and culminating in Chiloguembelina, and the other trochospiral, represented by Trochoguembelitria and culminating in Globoconusa. We have re-examined the genus Chiloguembelitria, another guembelitriid descended from Guembelitria and whose taxonomic validity had been questioned, it being considered a junior synonym of the latter. Nevertheless, Chiloguembelitria differs from Guembelitria mainly in the wall texture (pustulate to rugose vs. pore-mounded) and the position of the aperture (umbilical-extraumbilical to extraumbilical vs. umbilical). Chiloguembelitria shares its wall texture with Trochoguembelitria and some of the earliest specimens of Woodringina, suggesting that it played an important role in the evolution of early Danian guembelitriids, as it seems to be the most immediate ancestor of both trochospiral and biserial lineages. Morphological and morphostatistical analyses of Chiloguembelitria discriminate at least five species: Chg. danica, Chg. irregularis, and three new species: Chg. hofkeri, Chg. trilobata and Chg. biseriata.

Convergent evolution of pregnancy-specific glycoproteins in human and horse.

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Aleksic, Denis; Blaschke, Lisa; Mißbach, Sophie; Hänske, Jana; Weiß, Wiebke; Handler, Johannes; Zimmermann, Wolfgang; Cabrera-Sharp, Victoria; Read, Jordan E; de Mestre, Amanda M; O'Riordan, Ronan; Moore, Tom; Kammerer, Robert

2016-09-01

Pregnancy-specific glycoproteins (PSGs) are members of the carcinoembryonic antigen cell adhesion molecule (CEACAM) family that are secreted by trophoblast cells. PSGs may modulate immune, angiogenic and platelet responses during pregnancy. Until now, PSGs are only found in species that have a highly invasive (hemochorial) placentation including humans, mice and rats. Surprisingly, analyzing the CEACAM gene family of the horse, which has a non-invasive epitheliochorial placenta, with the exception of the transient endometrial cups, we identified equine CEACAM family members that seem to be related to PSGs of rodents and primates. We identified seven genes that encode secreted PSG-like CEACAMs Phylogenetic analyses indicate that they evolved independently from an equine CEACAM1-like ancestor rather than from a common PSG-like ancestor with rodents and primates. Significantly, expression of PSG-like genes (CEACAM44, CEACAM48, CEACAM49 and CEACAM55) was found in non-invasive as well as invasive trophoblast cells such as purified chorionic girdle cells and endometrial cup cells. Chorionic girdle cells are highly invasive trophoblast cells that invade the endometrium of the mare where they form endometrial cups and are in close contact with maternal immune cells. Therefore, the microenvironment of invasive equine trophoblast cells has striking similarities to the microenvironment of trophoblast cells in hemochorial placentas, suggesting that equine PSG-like CEACAMs and rodent and primate PSGs have undergone convergent evolution. This is supported by our finding that equine PSG-like CEACAM49 exhibits similar activity to certain rodent and human PSGs in a functional assay of platelet-fibrinogen binding. Our results have implications for understanding the evolution of PSGs and their functions in maternal-fetal interactions. © 2016 Society for Reproduction and Fertility.

Primary cortical folding in the human newborn: an early marker of later functional development

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Benders, M.; Borradori-Tolsa, C.; Cachia, A.; Lazeyras, F.; Ha-Vinh Leuchter, R.; Sizonenko, S. V.; Warfield, S. K.; Mangin, J. F.; Hüppi, 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 present long before the appearance of functional symptoms. So far, the precise mechanisms responsible for such alteration in the convolution pattern during intra-uterine or post-natal development are still poorly understood. Here we compared anatomical and functional brain development in vivo among 45 premature newborns who experienced different intra-uterine environments: 22 normal singletons, 12 twins and 11 newborns with intrauterine growth restriction (IUGR). Using magnetic resonance imaging (MRI) and dedicated post-processing tools, we investigated early disturbances in cortical formation at birth, over the developmental period critical for the emergence of convolutions (26–36 weeks of gestational age), and defined early ‘endophenotypes’ of sulcal development. We demonstrated that twins have a delayed but harmonious maturation, with reduced surface and sulcation index compared to singletons, whereas the gyrification of IUGR newborns is discordant to the normal developmental trajectory, with a more pronounced reduction of surface in relation to the sulcation index compared to normal newborns. Furthermore, we showed that these structural measurements of the brain at birth are predictors of infants’ outcome at term equivalent age, for MRI-based cerebral volumes and neurobehavioural development evaluated with the assessment of preterm infant's behaviour (APIB). PMID:18587151

Measurement of the human esophageal cancer in an early stage with Raman spectroscopy

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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.

Human Dose-Response Data for Francisella tularensis and a Dose- and Time-Dependent Mathematical Model of Early-Phase Fever Associated with Tularemia After Inhalation Exposure.

Science.gov (United States)

McClellan, Gene; Coleman, Margaret; Crary, David; Thurman, Alec; Thran, Brandolyn

2018-04-25

Military health risk assessors, medical planners, operational planners, and defense system developers require knowledge of human responses to doses of biothreat agents to support force health protection and chemical, biological, radiological, nuclear (CBRN) defense missions. This article reviews extensive data from 118 human volunteers administered aerosols of the bacterial agent Francisella tularensis, strain Schu S4, which causes tularemia. The data set includes incidence of early-phase febrile illness following administration of well-characterized inhaled doses of F. tularensis. Supplemental data on human body temperature profiles over time available from de-identified case reports is also presented. A unified, logically consistent model of early-phase febrile illness is described as a lognormal dose-response function for febrile illness linked with a stochastic time profile of fever. Three parameters are estimated from the human data to describe the time profile: incubation period or onset time for fever; rise time of fever; and near-maximum body temperature. Inhaled dose-dependence and variability are characterized for each of the three parameters. These parameters enable a stochastic model for the response of an exposed population through incorporation of individual-by-individual variability by drawing random samples from the statistical distributions of these three parameters for each individual. This model provides risk assessors and medical decisionmakers reliable representations of the predicted health impacts of early-phase febrile illness for as long as one week after aerosol exposures of human populations to F. tularensis. © 2018 Society for Risk Analysis.

Shining evolutionary light on human sleep and sleep disorders.

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Nunn, Charles L; Samson, David R; Krystal, Andrew D

2016-01-01

Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep-i.e. 'why' sleep evolved-remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalian sleep to better understand sleep along the human lineage and in the modern world. Compared to other primates, sleep in great apes has undergone substantial evolutionary change, with all great apes building a sleeping platform or 'nest'. Further evolutionary change characterizes human sleep, with humans having the shortest sleep duration, yet the highest proportion of rapid eye movement sleep among primates. These changes likely reflect that our ancestors experienced fitness benefits from being active for a greater portion of the 24-h cycle than other primates, potentially related to advantages arising from learning, socializing and defending against predators and hostile conspecifics. Perspectives from evolutionary medicine have implications for understanding sleep disorders; we consider these perspectives in the context of insomnia, narcolepsy, seasonal affective disorder, circadian rhythm disorders and sleep apnea. We also identify how human sleep today differs from sleep through most of human evolution, and the implications of these changes for global health and health disparities. More generally, our review highlights the importance of phylogenetic comparisons in understanding human health, including well-known links between sleep, cognitive performance and health in humans. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

Spatiotemporal distribution of PAX6 and MEIS2 expression and total cell numbers in the ganglionic eminence in the early developing human forebrain

DEFF Research Database (Denmark)

Larsen, Karen B; Lutterodt, Melissa C; Laursen, Henning

2010-01-01

The development of the human neocortex is a complex and highly regulated process involving a time-related expression of many transcription factors including the homeobox genes Pax6 and Meis2. During early development, Pax6 is expressed in nuclei of radial glia cells in the neocortical proliferative...... in the same time window. We demonstrate by in situ hybridization and immunohistochemistry that the two homeobox genes are expressed during early fetal brain development in humans. PAX6 mRNA and protein were located in the proliferative zones of the neocortex and in single cells in the cortical preplate at 7...... in the proliferative zones of the human fetal neocortex and a higher expression of MEIS2 than PAX6 was observed in these areas at 9 fetal weeks. Further, MEIS2 was expressed at a very high level in the developing ganglionic eminence and at a more moderate level in the cortical plate....

Early impairment of gut function and gut flora supporting a role for alteration of gastrointestinal mucosa in human immunodeficiency virus pathogenesis

NARCIS (Netherlands)

Gori, Andrea; Tincati, Camilla; Rizzardini, Giuliano; Torti, Carlo; Quirino, Tiziana; Haarman, Monique; Ben Amor, Kaouther; van Schaik, Jacqueline; Vriesema, Aldwin; Knol, Jan; Marchetti, Giulia; Welling, Gjalt; Clerici, Mario

Our results show that impairment of the gastrointestinal tracts in human immunodeficiency virus (HIV)-positive patients is present in the early phases of HIV disease. This impairment is associated with alterations in gut microbiota and intestinal inflammatory parameters. These findings support the

High-density rhesus macaque oligonucleotide microarray design using early-stage rhesus genome sequence information and human genome annotations

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Magness Charles L

2007-01-01

Full Text Available Abstract Background Until recently, few genomic reagents specific for non-human primate research have been available. To address this need, we have constructed a macaque-specific high-density oligonucleotide microarray by using highly fragmented low-pass sequence contigs from the rhesus genome project together with the detailed sequence and exon structure of the human genome. Using this method, we designed oligonucleotide probes to over 17,000 distinct rhesus/human gene orthologs and increased by four-fold the number of available genes relative to our first-generation expressed sequence tag (EST-derived array. Results We constructed a database containing 248,000 exon sequences from 23,000 human RefSeq genes and compared each human exon with its best matching sequence in the January 2005 version of the rhesus genome project list of 486,000 DNA contigs. Best matching rhesus exon sequences for each of the 23,000 human genes were then concatenated in the proper order and orientation to produce a rhesus "virtual transcriptome." Microarray probes were designed, one per gene, to the region closest to the 3' untranslated region (UTR of each rhesus virtual transcript. Each probe was compared to a composite rhesus/human transcript database to test for cross-hybridization potential yielding a final probe set representing 18,296 rhesus/human gene orthologs, including transcript variants, and over 17,000 distinct genes. We hybridized mRNA from rhesus brain and spleen to both the EST- and genome-derived microarrays. Besides four-fold greater gene coverage, the genome-derived array also showed greater mean signal intensities for genes present on both arrays. Genome-derived probes showed 99.4% identity when compared to 4,767 rhesus GenBank sequence tag site (STS sequences indicating that early stage low-pass versions of complex genomes are of sufficient quality to yield valuable functional genomic information when combined with finished genome information from

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

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Susanne Shultz

Full Text Available 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.

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

Science.gov (United States)

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.

The hominins: a very conservative tribe? Last common ancestors, plasticity and ecomorphology in Hominidae. Or, What's in a name?

Science.gov (United States)

Crompton, Robin Huw

2016-04-01

In the early 20th century the dominant paradigm for the ecological context of the origins of human bipedalism was arboreal suspension. In the 1960s, however, with recognition of the close genetic relationship of humans, chimpanzees and bonobos, and with the first field studies of mountain gorillas and common chimpanzees, it was assumed that locomotion similar to that of common chimpanzees and mountain gorillas, which appeared to be dominated by terrestrial knuckle-walking, must have given rise to human bipedality. This paradigm has been popular, if not universally dominant, until very recently. However, evidence that neither the knuckle-walking or vertical climbing of these apes is mechanically similar to human bipedalism, as well as the hand-assisted bipedality and orthograde clambering of orang-utans, has cast doubt on this paradigm. It now appears that the dominance of terrestrial knuckle-walking in mountain gorillas is an artefact seen only in the extremes of their range, and that both mountain and lowland gorillas have a generalized orthogrady similar to that seen in orang-utans. These data, together with evidence for continued arboreal competence in humans, mesh well with an increasing weight of fossil evidence suggesting that a mix of orang-utan and gorilla-like arboreal locomotion and upright terrestrial bipedalism characterized most australopiths. The late split date of the panins, corresponding to dates for separation of Homo and Australopithecus, leads to the speculation that competition with chimpanzees, as appears to exist today with gorillas, may have driven ecological changes in hominins and perhaps cladogenesis. However, selection for ecological plasticity and morphological conservatism is a core characteristic of Hominidae as a whole, including Hominini. © 2015 Anatomical Society.

The vertebrate ancestral repertoire of visual opsins, transducin alpha subunits and oxytocin/vasopressin receptors was established by duplication of their shared genomic region in the two rounds of early vertebrate genome duplications.

Science.gov (United States)

Lagman, David; Ocampo Daza, Daniel; Widmark, Jenny; Abalo, Xesús M; Sundström, Görel; Larhammar, Dan

2013-11-02

Vertebrate color vision is dependent on four major color opsin subtypes: RH2 (green opsin), SWS1 (ultraviolet opsin), SWS2 (blue opsin), and LWS (red opsin). Together with the dim-light receptor rhodopsin (RH1), these form the family of vertebrate visual opsins. Vertebrate genomes contain many multi-membered gene families that can largely be explained by the two rounds of whole genome duplication (WGD) in the vertebrate ancestor (2R) followed by a third round in the teleost ancestor (3R). Related chromosome regions resulting from WGD or block duplications are said to form a paralogon. We describe here a paralogon containing the genes for visual opsins, the G-protein alpha subunit families for transducin (GNAT) and adenylyl cyclase inhibition (GNAI), the oxytocin and vasopressin receptors (OT/VP-R), and the L-type voltage-gated calcium channels (CACNA1-L). Sequence-based phylogenies and analyses of conserved synteny show that the above-mentioned gene families, and many neighboring gene families, expanded in the early vertebrate WGDs. This allows us to deduce the following evolutionary scenario: The vertebrate ancestor had a chromosome containing the genes for two visual opsins, one GNAT, one GNAI, two OT/VP-Rs and one CACNA1-L gene. This chromosome was quadrupled in 2R. Subsequent gene losses resulted in a set of five visual opsin genes, three GNAT and GNAI genes, six OT/VP-R genes and four CACNA1-L genes. These regions were duplicated again in 3R resulting in additional teleost genes for some of the families. Major chromosomal rearrangements have taken place in the teleost genomes. By comparison with the corresponding chromosomal regions in the spotted gar, which diverged prior to 3R, we could time these rearrangements to post-3R. We present an extensive analysis of the paralogon housing the visual opsin, GNAT and GNAI, OT/VP-R, and CACNA1-L gene families. The combined data imply that the early vertebrate WGD events contributed to the evolution of vision and the

Speleothem evidence for the greening of the Sahara and its implications for the early human dispersal out of sub-Saharan Africa

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El-Shenawy, Mohammed I.; Kim, Sang-Tae; Schwarcz, Henry P.; Asmerom, Yemane; Polyak, Victor J.

2018-05-01

Although there is a consensus that there were wet periods (greening events) in the Sahara in the past, the spatial extent and the timing of these greening events are still in dispute, yet critical to our understanding of the early human dispersal out of Africa. Our U-series dates of speleothems from the Northeastern Sahara (Wadi Sannur cave, Egypt) reveal that the periods of speleothem growth were brief and restricted to the interglacial Marine Isotope Stages MIS 5.5, MIS 7.3, and the early MIS 9 with a remarkable absence of the Holocene deposition of speleothems. These growth periods of Wadi Sannur cave speleothems correspond to periods of high rainfall and spread of vegetation (green Sahara). Distinct low δ18O values of speleothems indicate a distal moisture source that we interpret to be the Atlantic Ocean. These two lines of evidence from the Wadi Sannur speleothems thus suggest that maximal northward shifts in the West African monsoon system occurred during the growth periods of the speleothems, leading to greening of the Sahara, facilitating human migration into Eurasia. The periods of speleothem growth at Wadi Sannur cave are contemporaneous with important archeological events: (1) the earliest occurrence of the Middle Stone Age assemblages and Homo sapiens in North Africa (Jebel Irhoud), suggesting wide spread of greening conditions over the East-West transect of the Sahara, (2) the sharp technological break between the Acheulo-Yabrudian and the Mousterian industries, and (3) the arrival of Homo sapiens in Levant, indicating a key role of the Sahara route in early human dispersal out of Africa.

Percussive technology in human evolution: an introduction to a comparative approach in fossil and living primates.

Science.gov (United States)

de la Torre, Ignacio; Hirata, Satoshi

2015-11-19

Percussive technology is part of the behavioural suite of several fossil and living primates. Stone Age ancestors used lithic artefacts in pounding activities, which could have been most important in the earliest stages of stone working. This has relevant evolutionary implications, as other primates such as chimpanzees and some monkeys use stone hammer-and-anvil combinations to crack hard-shelled foodstuffs. Parallels between primate percussive technologies and early archaeological sites need to be further explored in order to assess the emergence of technological behaviour in our evolutionary line, and firmly establish bridges between Primatology and Archaeology. What are the anatomical, cognitive and ecological constraints of percussive technology? How common are percussive activities in the Stone Age and among living primates? What is their functional significance? How similar are archaeological percussive tools and those made by non-human primates? This issue of Phil. Trans. addresses some of these questions by presenting case studies with a wide chronological, geographical and disciplinary coverage. The studies presented here cover studies of Brazilian capuchins, captive chimpanzees and chimpanzees in the wild, research on the use of percussive technology among modern humans and recent hunter-gatherers in Australia, the Near East and Europe, and archaeological examples of this behaviour from a million years ago to the Holocene. In summary, the breadth and depth of research compiled here should make this issue of Philosophical Transactions of the Royal Society B, a landmark step forward towards a better understanding of percussive technology, a unique behaviour shared by some modern and fossil primates. © 2015 The Author(s).

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

Science.gov (United States)

Charlier, Philippe; Huynh-Charlier, Isabelle; Poupon, Joël; Lancelot, Eloïse; Campos, Paula F; Favier, Dominique; Jeannel, Gaël-François; Bonati, Maurizio Rippa; de la Grandmaison, Geoffroy Lorin; Hervé, Christian

2014-05-12

Medieval autopsy practice is very poorly known in Western Europe, due to a lack of both descriptive medico-surgical texts and conserved dissected human remains. This period is currently considered the dark ages according to a common belief of systematic opposition of Christian religious authorities to the opening of human cadavers. The identification in a private collection of an autopsied human individual dated from the 13(th) century A.D. is an opportunity for better knowledge of such practice in this chrono-cultural context, i.e. the early origins of occidental dissections. A complete forensic anthropological procedure was carried out, completed by radiological and elemental analyses. The complete procedure of this body opening and internal organs exploration is explained, and compared with historical data about forensic and anatomical autopsies from this period. During the analysis, a red substance filling all arterial cavities, made of mercury sulfide (cinnabar) mixed with vegetal oil (oleic and palmitic acids) was identified; it was presumably used to highlight vascularization by coloring in red such vessels, and help in the preservation of the body. Of particular interest for the description of early medical and anatomical knowledge, this "human preparation" is the oldest known yet, and is particularly important for the fields of history of medicine, surgery and anatomical practice.

Humanizing Aggregated Data: Developing Personas to Prioritize User Needs for Earthquake Early Warning

Science.gov (United States)

Burkett, E. R.; Jayanty, N. K.; Sellnow, D. D.; Given, D. D.; DeGroot, R. M.

2016-12-01

Methods that use storytelling to gather and synthesize data from people can be advantageous in understanding user needs and designing successful communication products. Using a multidisciplinary approach, we research and prioritize user needs for the ShakeAlert Earthquake Early Warning system (http://pubs.usgs.gov/fs/2014/3083/), drawing on best practices from social and behavioral science, risk communication, and human-centered design. We apply quantitative and qualitative human data collection methods including user surveys, interviews, journey maps, personas, and scenarios. Human-centered design methods leverage storytelling (a) in the acquisition of qualitative behavioral data (e.g. with journey mapping), (b) through goal-driven behaviors and needs that are synthesized into a persona as a composite model of the data, and (c) within context scenarios (the story plot or projected circumstances) in which the persona is placed in context to inform the design of relevant and usable products or services. ShakeAlert, operated by the USGS and partners, has transitioned into a production prototype phase in which users are permitted to begin testing pilot implementations to take protective actions in response to an earthquake alert. While a subset of responses will be automated (e.g., opening fire house doors), other applications of the technology will alert individuals by broadcast, public address, or mobile device notifications and require self-protective behavioral decisions (e.g., "Drop, Cover, and Hold On"). To better understand ShakeAlert user decisions and needs, we use human-centered design methods to synthesize aggregated behavioral data into "personas," which model the common behavioral patterns that can be used to guide plans for the ShakeAlert interface, messaging, and training. We present user data, methods, and resulting personas that will inform decisions moving forward to shape ShakeAlert messaging and training that will be most usable by alert recipients.

The proteomic complexity and rise of the primordial ancestor of diversified life

Directory of Open Access Journals (Sweden)

Kim Kyung

2011-05-01

Full Text Available Abstract Background The last universal common ancestor represents the primordial cellular organism from which diversified life was derived. This urancestor accumulated genetic information before the rise of organismal lineages and is considered to be either a simple 'progenote' organism with a rudimentary translational apparatus or a more complex 'cenancestor' with almost all essential biological processes. Recent comparative genomic studies support the latter model and propose that the urancestor was similar to modern organisms in terms of gene content. However, most of these studies were based on molecular sequences, which are fast evolving and of limited value for deep evolutionary explorations. Results Here we engage in a phylogenomic study of protein domain structure in the proteomes of 420 free-living fully sequenced organisms. Domains were defined at the highly conserved fold superfamily (FSF level of structural classification and an iterative phylogenomic approach was used to reconstruct max_set and min_set FSF repertoires as upper and lower bounds of the urancestral proteome. While the functional make up of the urancestral sets was complex, they represent only 5-11% of the 1,420 FSFs of extant proteomes and their make up and reuse was at least 5 and 3 times smaller than proteomes of free-living organisms, repectively. Trees of proteomes reconstructed directly from FSFs or from molecular functions, which included the max_set and min_set as articial taxa, showed that urancestors were always placed at their base and rooted the tree of life in Archaea. Finally, a molecular clock of FSFs suggests the min_set reflects urancestral genetic make up more reliably and confirms diversified life emerged about 2.9 billion years ago during the start of planet oxygenation. Conclusions The minimum urancestral FSF set reveals the urancestor had advanced metabolic capabilities, was especially rich in nucleotide metabolism enzymes, had pathways for the

Cellular homeoproteins, SATB1 and CDP, bind to the unique region between the human cytomegalovirus UL127 and major immediate-early genes

International Nuclear Information System (INIS)

Lee Jialing; Klase, Zachary; Gao Xiaoqi; Caldwell, Jeremy S.; Stinski, Mark F.; Kashanchi, Fatah; Chao, S.-H.

2007-01-01

An AT-rich region of the human cytomegalovirus (CMV) genome between the UL127 open reading frame and the major immediate-early (MIE) enhancer is referred to as the unique region (UR). It has been shown that the UR represses activation of transcription from the UL127 promoter and functions as a boundary between the divergent UL127 and MIE genes during human CMV infection [Angulo, A., Kerry, D., Huang, H., Borst, E.M., Razinsky, A., Wu, J., Hobom, U., Messerle, M., Ghazal, P., 2000. Identification of a boundary domain adjacent to the potent human cytomegalovirus enhancer that represses transcription of the divergent UL127 promoter. J. Virol. 74 (6), 2826-2839; Lundquist, C.A., Meier, J.L., Stinski, M.F., 1999. A strong negative transcriptional regulatory region between the human cytomegalovirus UL127 gene and the major immediate-early enhancer. J. Virol. 73 (11), 9039-9052]. A putative forkhead box-like (FOX-like) site, AAATCAATATT, was identified in the UR and found to play a key role in repression of the UL127 promoter in recombinant virus-infected cells [Lashmit, P.E., Lundquist, C.A., Meier, J.L., Stinski, M.F., 2004. Cellular repressor inhibits human cytomegalovirus transcription from the UL127 promoter. J. Virol. 78 (10), 5113-5123]. However, the cellular factors which associate with the UR and FOX-like region remain to be determined. We reported previously that pancreatic-duodenal homeobox factor-1 (PDX1) bound to a 45-bp element located within the UR [Chao, S.H., Harada, J.N., Hyndman, F., Gao, X., Nelson, C.G., Chanda, S.K., Caldwell, J.S., 2004. PDX1, a Cellular Homeoprotein, Binds to and Regulates the Activity of Human Cytomegalovirus Immediate Early Promoter. J. Biol. Chem. 279 (16), 16111-16120]. Here we demonstrate that two additional cellular homeoproteins, special AT-rich sequence binding protein 1 (SATB1) and CCAAT displacement protein (CDP), bind to the human CMV UR in vitro and in vivo. Furthermore, CDP is identified as a FOX-like binding protein

Interferon-alpha mediates restriction of human immunodeficiency virus type-1 replication in primary human macrophages at an early stage of replication.

Directory of Open Access Journals (Sweden)

Kelly M Cheney

2010-10-01

Full Text Available Type I interferons (IFNα and β are induced directly in response to viral infection, resulting in an antiviral state for the cell. In vitro studies have shown that IFNα is a potent inhibitor of viral replication; however, its role in HIV-1 infection is incompletely understood. In this study we describe the ability of IFNα to restrict HIV-1 infection in primary human macrophages in contrast to peripheral blood mononuclear cells and monocyte-derived dendritic cells. Inhibition to HIV-1 replication in cells pretreated with IFNα occurred at an early stage in the virus life cycle. Late viral events such as budding and subsequent rounds of infection were not affected by IFNα treatment. Analysis of early and late HIV-1 reverse transcripts and integrated proviral DNA confirmed an early post entry role for IFNα. First strand cDNA synthesis was slightly reduced but late and integrated products were severely depleted, suggesting that initiation or the nucleic acid intermediates of reverse transcription are targeted. The depletion of integrated provirus is disproportionally greater than that of viral cDNA synthesis suggesting the possibility of a least an additional later target. A role for either cellular protein APOBEC3G or tetherin in this IFNα mediated restriction has been excluded. Vpu, previously shown by others to rescue a viral budding restriction by tetherin, could not overcome this IFNα induced effect. Determining both the viral determinants and cellular proteins involved may lead to novel therapeutic approaches. Our results add to the understanding of HIV-1 restriction by IFNα.

Early visual evoked potentials are modulated by eye position in humans induced by whole body rotations

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Petit Laurent

2004-09-01

Full Text Available Abstract Background To reach and grasp an object in space on the basis of its image cast on the retina requires different coordinate transformations that take into account gaze and limb positioning. Eye position in the orbit influences the image's conversion from retinotopic (eye-centered coordinates to an egocentric frame necessary for guiding action. Neuroimaging studies have revealed eye position-dependent activity in extrastriate visual, parietal and frontal areas that is along the visuo-motor pathway. At the earliest vision stage, the role of the primary visual area (V1 in this process remains unclear. We used an experimental design based on pattern-onset visual evoked potentials (VEP recordings to study the effect of eye position on V1 activity in humans. Results We showed that the amplitude of the initial C1 component of VEP, acknowledged to originate in V1, was modulated by the eye position. We also established that putative spontaneous small saccades related to eccentric fixation, as well as retinal disparity cannot explain the effects of changing C1 amplitude of VEP in the present study. Conclusions The present modulation of the early component of VEP suggests an eye position-dependent activity of the human primary visual area. Our findings also evidence that cortical processes combine information about the position of the stimulus on the retinae with information about the location of the eyes in their orbit as early as the stage of primary visual area.

Serum IgE and IgG4 against muscle larva excretory-secretory products during the early and late phases of human trichinellosis.

Science.gov (United States)

Calcagno, Marcela A; Forastiero, María A; Saracino, María P; Vila, Cecilia C; Venturiello, Stella M

2017-11-01

In human trichinellosis, the relevance of the presence and persistence of specific serum IgE and IgG4 during the early and late phases of infection is still controversial.The aim of this work was to determine the percentage of human sera presenting IgE and IgG4 against Trichinella spiralis muscle larvae excretory-secretory products as well as their levels during the early and late phases of the infection. The antigen recognition pattern by serum total immunoglobulins (IgGAM), IgE, and IgG4 was assessed over time. Serum samples during early and late phases were analyzed by ELISA and immunoelectrotransfer blot (IETB).Results showed that (a)-IgE and IgG4 are present at constant levels in both phases; (b)-IgE recognized the glycoproteins of ~ 45 and ~ 55 kDa and IgG4 only the ~ 45 kDa; (c)-in the late phase, the percentage of specific IgE positive sera was higher than that of specific IgG4 by IETB; while in serum samples taken during the early phase, no differences were found between both isotypes; (d)-both isotypes displayed different glycoprotein recognition patterns: the pattern corresponding to IgE was coincident with that of IgGAM, comprising seven glycoproteins (ranging from ~ 116 to ~ 29 kDa), whereas IgG4 revealed four glycoproteins (ranging from ~ 97 to ~ 45 kDa), showing a different sera recognition percentage depending on the phase studied.In conclusion, IgE and IgG4 cannot be considered exclusive isotypes of neither the early nor the late phase of infection and they are as useful as the detection of total antibodies in the early diagnosis.

FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells

International Nuclear Information System (INIS)

Sui, Lina; Mfopou, Josué K.; Geens, Mieke; Sermon, Karen; Bouwens, Luc

2012-01-01

Highlights: ► Deep study the FGF signaling role during DE specification in the context of hESCs. ► DE differentiation from hESCs has an early dependence on FGF signaling. ► A serum-free DE protocol is developed based on the findings. ► The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study, we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.

Terrestrial origin of viviparity in mesozoic marine reptiles indicated by early triassic embryonic fossils.

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Ryosuke Motani

Full Text Available Viviparity in Mesozoic marine reptiles has traditionally been considered an aquatic adaptation. We report a new fossil specimen that strongly contradicts this traditional interpretation. The new specimen contains the oldest fossil embryos of Mesozoic marine reptile that are about 10 million years older than previous such records. The fossil belongs to Chaohusaurus (Reptilia, Ichthyopterygia, which is the oldest of Mesozoic marine reptiles (ca. 248 million years ago, Early Triassic. This exceptional specimen captures an articulated embryo in birth position, with its skull just emerged from the maternal pelvis. Its headfirst birth posture, which is unlikely to be a breech condition, strongly indicates a terrestrial origin of viviparity, in contrast to the traditional view. The tail-first birth posture in derived ichthyopterygians, convergent with the conditions in whales and sea cows, therefore is a secondary feature. The unequivocally marine origin of viviparity is so far not known among amniotes, a subset of vertebrate animals comprising mammals and reptiles, including birds. Therefore, obligate marine amniotes appear to have evolved almost exclusively from viviparous land ancestors. Viviparous land reptiles most likely appeared much earlier than currently thought, at least as early as the recovery phase from the end-Permian mass extinction.

Biological Effects of Sunlight, Ultraviolet Radiation, Visible Light, Infrared Radiation and Vitamin D for Health.

Science.gov (United States)

Holick, Michael F

2016-03-01

Humans evolved in sunlight and had depended on sunlight for its life giving properties that was appreciated by our early ancestors. However, for more than 40 years the lay press and various medical and dermatology associations have denounced sun exposure because of its association with increased risk for skin cancer. The goal of this review is to put into perspective the many health benefits that have been associated with exposure to sunlight, ultraviolet A (UVA) ultraviolet B (UVB), visible and infrared radiation. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The early human germ cell lineage does not express SOX2 during in vivo development or upon in vitro culture

DEFF Research Database (Denmark)

Perrett, Rebecca M; Turnpenny, Lee; Eckert, Judith J

2008-01-01

NANOG, POU5F1, and SOX2 are required by the inner cell mass of the blastocyst and act cooperatively to maintain pluripotency in both mouse and human embryonic stem cells. Inadequacy of any one of them causes loss of the undifferentiated state. Mouse primordial germ cells (PGCs), from which...... pluripotent embryonic germ cells (EGCs) are derived, also express POU5F1, NANOG, and SOX2. Thus, a similar expression profile has been predicted for human PGCs. Here we show by RT-PCR, immunoblotting, and immunohistochemistry that human PGCs express POU5F1 and NANOG but not SOX2, with no evidence...... of redundancy within the group B family of human SOX genes. Although lacking SOX2, proliferative human germ cells can still be identified in situ during early development and are capable of culture in vitro. Surprisingly, with the exception of FGF4, many stem cell-restricted SOX2 target genes remained detected...

Early Learning and Educational Technology Policy Brief

Science.gov (United States)

Lee, Joan

2016-01-01

Recognizing the growth of technology use in early learning settings, the U.S. Department of Education and U.S. Department of Health and Human Services collaborated in the development of the "Early Learning and Educational Technology Policy Brief" to promote developmentally appropriate use of technology in homes and early learning…

Review of Beyond Illustration: 2D and 3D Digital Tools for Discovery in Archaeology [Book

Directory of Open Access Journals (Sweden)

Melissa Terras

2010-06-01

Full Text Available The creation of images has been an activity since the beginning of human society: our early ancestors painted or carved rocks with depictions of their lifestyles and beliefs. Rocks are not very portable, however, and humans like to share their visualisations and the knowledge contained within them. Much investment in technology has focused on the ability to create, replicate and disseminate visual information, from early print materials to attempts at chemical photography and recently, the development of ever more complex computational methods to represent visual information in a variety of ways. Visualisations are an important means of communication, a source of information and a focus of both social interaction and scholarly activity. Images and visualisations play an important role in cultural and social history, can contain valuable historical information and are used more and more in academic research that aims to study culture in its widest sense: focussing on artefacts and cultural produce.

Human hyoid bones from the middle Pleistocene site of the Sima de los Huesos (Sierra de Atapuerca, Spain).

Science.gov (United States)

Martínez, I; Arsuaga, J L; Quam, R; Carretero, J M; Gracia, A; Rodríguez, L

2008-01-01

This study describes and compares two hyoid bones from the middle Pleistocene site of the Sima de los Huesos in the Sierra de Atapuerca (Spain). The Atapuerca SH hyoids are humanlike in both their morphology and dimensions, and they clearly differ from the hyoid bones of chimpanzees and Australopithecus afarensis. Their comparison with the Neandertal specimens Kebara 2 and SDR-034 makes it possible to begin to approach the question of temporal variation and sexual dimorphism in this bone in fossil humans. The results presented here show that the degree of metric and anatomical variation in the fossil sample was similar in magnitude and kind to living humans. Modern hyoid morphology was present by at least 530 kya and appears to represent a shared derived feature of the modern human and Neandertal evolutionary lineages inherited from their last common ancestor.

The fine structure of human germ layers in vivo: clues to the early differentiation of embryonic stem cells in vitro.

Science.gov (United States)

Sathananthan, Henry; Selvaraj, Kamala; Clark, Joan

2011-08-01

The fine structure of the three germ layers in human ectopic embryos (stage 7) have been documented by digital light and electron microscopy. The formation of ectoderm, endoderm and mesoderm and notochordal cells, and also the extraembryonic membranes, amnion and yolk sac, are imaged. The germ layers give rise to all the cells and tissues of the human body. Possible clues to the early differentiation of embryonic stem cells (ESC) in vitro were obtained, since these events are more or less mimicked in cultures of ESC derived from the inner cell mass of human blastocysts. The findings are discussed with reference to previous studies on the fine structure of ESC using the same technique. Copyright © 2011. Published by Elsevier Ltd.

The role of environmental change in the expansion of early modern humans in the Levant - what can we learn from mollusc shells

DEFF Research Database (Denmark)

Prendergast, Amy; Bosch, Marjolein D.; Mannino, Marcello

and Manot Cave in Israel. These highly resolved environmental records, coupled with well dated archaeological sequences provide a framework for assessing the complex interplay between early modern humans and their local environments. We found evidence for fluctuating temperature, rainfall and seasonality...... regimes, indicating that modern human populations were somewhat resilient to the resource uncertainty that would have accompanied these changing temperature and seasonality regimes. These paired cultural-environmental records have enabled an examination of hominin-environment interactions during critical...

The ecological imperative and its application to ethical issues in human genetic technology

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W. Malcolm Byrnes

2003-08-01

Full Text Available As a species, we are on the cusp of being able to alter that which makes us uniquely human, our genome. Two new genetic technologies, embryo selection and germline engineering, are either in use today or may be developed in the future. Embryo selection acts to alter the human gene pool, reducing genetic diversity, while germline engineering will have the ability to alter directly the genomes of engineered individuals. Our genome has come to be what it is through an evolutionary process extending over millions of years, a process that has involved exceedingly complex and unpredictable interactions between ourselves or our ancestors and myriad other life forms within Earth's biosphere. In this paper, the ecological imperativ e, which states that we must not alter the human genome or the collective human genetic inheritance, will be introduced. It will be argued based on ecological principles that embryo selection and germline engineering are unethical and unwise because they will diminish our survivability as a species, will disrupt our relationship with the natural world, and will destroy the very basis of that which makes us human.

FOXM1 upregulation is an early event in human squamous cell carcinoma and it is enhanced by nicotine during malignant transformation.

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Emilios Gemenetzidis

Full Text Available Cancer associated with smoking and drinking remains a serious health problem worldwide. The survival of patients is very poor due to the lack of effective early biomarkers. FOXM1 overexpression is linked to the majority of human cancers but its mechanism remains unclear in head and neck squamous cell carcinoma (HNSCC.FOXM1 mRNA and protein expressions were investigated in four independent cohorts (total 75 patients consisting of normal, premalignant and HNSCC tissues and cells using quantitative PCR (qPCR, expression microarray, immunohistochemistry and immunocytochemistry. Effect of putative oral carcinogens on FOXM1 transcriptional activity was dose-dependently assayed and confirmed using a FOXM1-specific luciferase reporter system, qPCR, immunoblotting and short-hairpin RNA interference. Genome-wide single nucleotide polymorphism (SNP array was used to 'trace' the genomic instability signature pattern in 8 clonal lines of FOXM1-induced malignant human oral keratinocytes. Furthermore, acute FOXM1 upregulation in primary oral keratinocytes directly induced genomic instability. We have shown for the first time that overexpression of FOXM1 precedes HNSCC malignancy. Screening putative carcinogens in human oral keratinocytes surprisingly showed that nicotine, which is not perceived to be a human carcinogen, directly induced FOXM1 mRNA, protein stabilisation and transcriptional activity at concentrations relevant to tobacco chewers. Importantly, nicotine also augmented FOXM1-induced transformation of human oral keratinocytes. A centrosomal protein CEP55 and a DNA helicase/putative stem cell marker HELLS, both located within a consensus loci (10q23, were found to be novel targets of FOXM1 and their expression correlated tightly with HNSCC progression.This study cautions the potential co-carcinogenic effect of nicotine in tobacco replacement therapies. We hypothesise that aberrant upregulation of FOXM1 may be inducing genomic instability through a

Comparative study of MSX-2, DLX-5, and DLX-7 gene expression during early human tooth development.

Science.gov (United States)

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.

Human diet in the early medieval period: Tooth wear, mastication, enamel thickness and its relationship to social stratification

Czech Academy of Sciences Publication Activity Database

Ibrová, A.; Dupej, J.; Stránská, Petra; Velemínský, P.; Poláček, Lumír; Velemínská, J.

2017-01-01

Roč. 162, S64 (2017), s. 226 ISSN 0002-9483. [Annual Meeting of the American Association of Physical Anthropologists /86./. 19.04.2017-22.04.2017, New Orleans] Institutional support: RVO:67985912 ; RVO:68081758 Keywords : Early Middle Ages * human diet * anthropology * tooth wear * Central Europe Subject RIV: AC - Archeology, Anthropology, Ethnology; AC - Archeology, Anthropology, Ethnology (ARUB-Q) OBOR OECD: Archaeology; Archaeology (ARUB-Q) http://onlinelibrary.wiley.com/doi/10.1002/ajpa.23210/pdf

Early Head Start Evaluation

Data.gov (United States)

U.S. Department of Health & Human Services — Longitudinal information from an evaluation where children were randomly assigned to Early Head Start or community services as usual;direct assessments and...

Parent-offspring conflict and the persistence of pregnancy-induced hypertension in modern humans

DEFF Research Database (Denmark)

Hartsteen, Birgitte Hollegaard; Byars, Sean Geoffrey; Lykke, Jacob

2013-01-01

Preeclampsia is a major cause of perinatal mortality and disease affecting 5-10% of all pregnancies worldwide, but its etiology remains poorly understood despite considerable research effort. Parent-offspring conflict theory suggests that such hypertensive disorders of pregnancy may have evolved...... towards the end of pregnancy in order to explain why these disorders have not been removed by natural selection in our hunter-gatherer ancestors. We analyzed >750,000 live births in the Danish National Patient Registry and all registered medical diagnoses for up to 30 years after birth. We show...... that early PIH leading to improved postpartum survival and health represents a balanced compromise between the reproductive interests of parents and offspring, whereas later onset of PIH may reflect an unbalanced parent-offspring conflict at the detriment of maternal and offspring health....

Human radiation studies: Remembering the early years: Oral history of cell biologist Don Francis Petersen, Ph.D., conducted November 29, 1994

International Nuclear Information System (INIS)

1995-08-01

This report is a transcript of an interview of Dr. Don Francis Petersen by representatives of the US DOE Office of Human Radiation Experiments. Dr. Petersen was selected for this interview because of his long research career at Los Alamos and his knowledge of the Atomic Energy Commission's biomedical program. Dr. Petersen did not personally conduct research on human subjects. After a brief biographical sketch Dr. Petersen discusses his remembrances of the early use of radionuclides as biological tracers, aspects of nuclear weapons testing in the 1940's and 1950's including fallout studies, the means by which research projects were approved, use of humans in the whole-body counter, and the Health Division Biomedical responsibilities

Human radiation studies: Remembering the early years: Oral history of cell biologist Don Francis Petersen, Ph.D., conducted November 29, 1994

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-08-01

This report is a transcript of an interview of Dr. Don Francis Petersen by representatives of the US DOE Office of Human Radiation Experiments. Dr. Petersen was selected for this interview because of his long research career at Los Alamos and his knowledge of the Atomic Energy Commission`s biomedical program. Dr. Petersen did not personally conduct research on human subjects. After a brief biographical sketch Dr. Petersen discusses his remembrances of the early use of radionuclides as biological tracers, aspects of nuclear weapons testing in the 1940`s and 1950`s including fallout studies, the means by which research projects were approved, use of humans in the whole-body counter, and the Health Division Biomedical responsibilities.

Early dissemination seeds metastasis in breast cancer

Science.gov (United States)

Hosseini, Hedayatollah; Obradović, Milan M.S.; Hoffmann, Martin; Harper, Kathryn; Sosa, Maria Soledad; Werner-Klein, Melanie; Nanduri, Lahiri Kanth; Werno, Christian; Ehrl, Carolin; Maneck, Matthias; Patwary, Nina; Haunschild, Gundula; Gužvić, Miodrag; Reimelt, Christian; Grauvogl, Michael; Eichner, Norbert; Weber, Florian; Hartkopf, Andreas; Taran, Florin-Andrei; Brucker, Sara Y.; Fehm, Tanja; Rack, Brigitte; Buchholz, Stefan; Spang, Rainer; Meister, Gunter; Aguirre-Ghiso, Julio A.; Klein, Christoph A.

2016-01-01

Accumulating data suggest that metastatic dissemination often occurs early during tumour formation but the mechanisms of early metastatic spread have not yet been addressed. Here, we studied metastasis in a HER2-driven mouse breast cancer model and found that progesterone-induced signalling triggered migration of cancer cells from early lesions shortly after HER2 activation, but promoted proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by elevated HER2 expression and increased tumour cell density involving miRNA-mediated progesterone receptor (PGR) down-regulation and was reversible. Cells from early, low-density lesions displayed more stemness features than cells from dense, advanced tumours, migrated more and founded more metastases. Strikingly, we found that at least 80% of metastases were derived from early disseminated cancer cells (DCC). Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination. PMID:27974799

Last glacial megafaunal death assemblage and early human occupation at Lake Menindee, southeastern Australia

Science.gov (United States)

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.

Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage.

Science.gov (United States)

Tulpule, Asmin; Lensch, M William; Miller, Justine D; Austin, Karyn; D'Andrea, Alan; Schlaeger, Thorsten M; Shimamura, Akiko; Daley, George Q

2010-04-29

Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. We have created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. Our data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA. This work illustrates how hESCs can provide unique insights into human development and further our understanding of genetic disease.

Safety, Pharmacokinetics, Immunogenicity, and Biodistribution of (186)Re-Labeled Humanized Monoclonal Antibody BIWA 4 (Bivatuzumab( in Patients with Early-Stage Breast Cancer.

NARCIS (Netherlands)

Koppe, M.; Schaijk, F. van; Roos, J.C.; Leeuwen, P.; Heider, K.H.; Kuthan, H.; Bleichrodt, R.P.

2004-01-01

The aim of this prospective study was to evaluate the safety, pharmacokinetics, immunogenicity, and biodistribution of (186)Re-labeled humanized anti-CD44v6 monoclonal antibody (MAb( BIWA 4 (Bivatuzumab( in 9 patients with early-stage breast cancer. Radioimmunoscintigraphy (RIS( was performed within

Different patterns of evolution in the centromeric and telomeric regions of group A and B haplotypes of the human killer cell Ig-like receptor locus.

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Chul-Woo Pyo

Full Text Available The fast evolving human KIR gene family encodes variable lymphocyte receptors specific for polymorphic HLA class I determinants. Nucleotide sequences for 24 representative human KIR haplotypes were determined. With three previously defined haplotypes, this gave a set of 12 group A and 15 group B haplotypes for assessment of KIR variation. The seven gene-content haplotypes are all combinations of four centromeric and two telomeric motifs. 2DL5, 2DS5 and 2DS3 can be present in centromeric and telomeric locations. With one exception, haplotypes having identical gene content differed in their combinations of KIR alleles. Sequence diversity varied between haplotype groups and between centromeric and telomeric halves of the KIR locus. The most variable A haplotype genes are in the telomeric half, whereas the most variable genes characterizing B haplotypes are in the centromeric half. Of the highly polymorphic genes, only the 3DL3 framework gene exhibits a similar diversity when carried by A and B haplotypes. Phylogenetic analysis and divergence time estimates, point to the centromeric gene-content motifs that distinguish A and B haplotypes having emerged ~6 million years ago, contemporaneously with the separation of human and chimpanzee ancestors. In contrast, the telomeric motifs that distinguish A and B haplotypes emerged more recently, ~1.7 million years ago, before the emergence of Homo sapiens. Thus the centromeric and telomeric motifs that typify A and B haplotypes have likely been present throughout human evolution. The results suggest the common ancestor of A and B haplotypes combined a B-like centromeric region with an A-like telomeric region.

Distinct Transcriptional and Alternative Splicing Signatures of Decidual CD4+ T Cells in Early Human Pregnancy

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Weihong Zeng

2017-06-01

Full Text Available Decidual CD4+ T (dCD4 T cells are crucial for the maternal-fetal immune tolerance required for a healthy pregnancy outcome. However, their molecular and functional characteristics are not well elucidated. In this study, we performed the first analysis of transcriptional and alternative splicing (AS landscapes for paired decidual and peripheral blood CD4+ T (pCD4 T cells in human early pregnancy using high throughput mRNA sequencing. Our data showed that dCD4 T cells are endowed with a unique transcriptional signature when compared to pCD4 T cells: dCD4 T cells upregulate 1,695 genes enriched in immune system process whereas downregulate 1,011 genes mainly related to mRNA catabolic process and the ribosome. Moreover, dCD4 T cells were observed to be at M phase, and show increased activation, proliferation, and cytokine production, as well as display an effector-memory phenotype and a heterogenous nature containing Th1, Th17, and Treg cell subsets. However, dCD4 T cells undergo a comparable number of upregulated and downregulated AS events, both of which are enriched in the genes related to cellular metabolic process. And the changes at the AS event level do not reflect measurable differences at the gene expression level in dCD4 T cells. Collectively, our findings provide a comprehensive portrait of the unique transcriptional signature and AS profile of CD4+ T cells in human decidua and help us gain more understanding of the functional characteristic of these cells during early pregnancy.

FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells

Energy Technology Data Exchange (ETDEWEB)

Sui, Lina, E-mail: linasui@vub.ac.be [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Mfopou, Josue K. [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Geens, Mieke; Sermon, Karen [Department of Embryology and Genetics, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Bouwens, Luc [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)

2012-09-28

Highlights: Black-Right-Pointing-Pointer Deep study the FGF signaling role during DE specification in the context of hESCs. Black-Right-Pointing-Pointer DE differentiation from hESCs has an early dependence on FGF signaling. Black-Right-Pointing-Pointer A serum-free DE protocol is developed based on the findings. Black-Right-Pointing-Pointer The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study, we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.

Early Evidence of Acheulean Settlement in Northwestern Europe - La Noira Site, a 700 000 Year-Old Occupation in the Center of France

Science.gov (United States)

Moncel, Marie-Hélène; Despriée, Jackie; Voinchet, Pierre; Tissoux, Hélène; Moreno, Davinia; Bahain, Jean-Jacques; Courcimault, Gilles; Falguères, Christophe

2013-01-01

The human settlement of Europe during Pleistocene times was sporadic and several stages have been recognized, both from paleaoanthropological and archaeological records. If the first phase of hominin occupation (as early as 1.4 Ma) seems mainly restricted to the southern part of the continent, the second phase, characterized by specific lithic tools (handaxes), is linked to Acheulean settlements and to the emergence of Homo heidelbergensis, the ancestor of Neanderthals. This phase reached northwestern Europe and is documented in numerous sites in Germany, Great Britain and northern France, generally after 600 ka. At la Noira (Brinay, Central France), the Middle Pleistocene alluvial formation of the Cher River covers an archaeological level associated with a slope deposit (diamicton). The lithic assemblage from this level includes Large Cutting Tools (LCTs), flakes and cores, associated with numerous millstone slabs. The lithic series is classified as Acheulean on the basis of both technological and typological analyses. Cryoturbation features indicate that the slope deposits and associated archaeological level were strongly frozen and disturbed after hominin occupation and before fluvial deposition. Eight sediment samples were dated by the electron spin resonance (ESR) method and the weighted average age obtained for the fluvial sands overlying the slope deposits is 665±55 ka. This age is older than previous chronological data placing the first European Acheulean assemblages north of 45th parallel north at around 500 ka and modifies our current vision of the initial peopling of northern Europe. Acheulean settlements are older than previously assumed and the oldest evidences are not only located in southern Europe. La Noira is the oldest evidence of Acheulean presence in north-western Europe and attests to the possibility of pioneering phases of Acheulean settlement which would have taken place on a Mode 1-type substratum as early as 700 ka. The lithic assemblage

Early evidence of Acheulean settlement in northwestern Europe--la Noira site, a 700,000 year-old occupation in the center of France.

Directory of Open Access Journals (Sweden)

Marie-Hélène Moncel

Full Text Available The human settlement of Europe during Pleistocene times was sporadic and several stages have been recognized, both from paleaoanthropological and archaeological records. If the first phase of hominin occupation (as early as 1.4 Ma seems mainly restricted to the southern part of the continent, the second phase, characterized by specific lithic tools (handaxes, is linked to Acheulean settlements and to the emergence of Homo heidelbergensis, the ancestor of Neanderthals. This phase reached northwestern Europe and is documented in numerous sites in Germany, Great Britain and northern France, generally after 600 ka. At la Noira (Brinay, Central France, the Middle Pleistocene alluvial formation of the Cher River covers an archaeological level associated with a slope deposit (diamicton. The lithic assemblage from this level includes Large Cutting Tools (LCTs, flakes and cores, associated with numerous millstone slabs. The lithic series is classified as Acheulean on the basis of both technological and typological analyses. Cryoturbation features indicate that the slope deposits and associated archaeological level were strongly frozen and disturbed after hominin occupation and before fluvial deposition. Eight sediment samples were dated by the electron spin resonance (ESR method and the weighted average age obtained for the fluvial sands overlying the slope deposits is 665±55 ka. This age is older than previous chronological data placing the first European Acheulean assemblages north of 45(th parallel north at around 500 ka and modifies our current vision of the initial peopling of northern Europe. Acheulean settlements are older than previously assumed and the oldest evidences are not only located in southern Europe. La Noira is the oldest evidence of Acheulean presence in north-western Europe and attests to the possibility of pioneering phases of Acheulean settlement which would have taken place on a Mode 1-type substratum as early as 700 ka. The

Early evidence of Acheulean settlement in northwestern Europe--la Noira site, a 700,000 year-old occupation in the center of France.

Science.gov (United States)

Moncel, Marie-Hélène; Despriée, Jackie; Voinchet, Pierre; Tissoux, Hélène; Moreno, Davinia; Bahain, Jean-Jacques; Courcimault, Gilles; Falguères, Christophe

2013-01-01

The human settlement of Europe during Pleistocene times was sporadic and several stages have been recognized, both from paleaoanthropological and archaeological records. If the first phase of hominin occupation (as early as 1.4 Ma) seems mainly restricted to the southern part of the continent, the second phase, characterized by specific lithic tools (handaxes), is linked to Acheulean settlements and to the emergence of Homo heidelbergensis, the ancestor of Neanderthals. This phase reached northwestern Europe and is documented in numerous sites in Germany, Great Britain and northern France, generally after 600 ka. At la Noira (Brinay, Central France), the Middle Pleistocene alluvial formation of the Cher River covers an archaeological level associated with a slope deposit (diamicton). The lithic assemblage from this level includes Large Cutting Tools (LCTs), flakes and cores, associated with numerous millstone slabs. The lithic series is classified as Acheulean on the basis of both technological and typological analyses. Cryoturbation features indicate that the slope deposits and associated archaeological level were strongly frozen and disturbed after hominin occupation and before fluvial deposition. Eight sediment samples were dated by the electron spin resonance (ESR) method and the weighted average age obtained for the fluvial sands overlying the slope deposits is 665±55 ka. This age is older than previous chronological data placing the first European Acheulean assemblages north of 45(th) parallel north at around 500 ka and modifies our current vision of the initial peopling of northern Europe. Acheulean settlements are older than previously assumed and the oldest evidences are not only located in southern Europe. La Noira is the oldest evidence of Acheulean presence in north-western Europe and attests to the possibility of pioneering phases of Acheulean settlement which would have taken place on a Mode 1-type substratum as early as 700 ka. The lithic assemblage

SPOC1-mediated antiviral host cell response is antagonized early in human adenovirus type 5 infection

DEFF Research Database (Denmark)

Schreiner, Sabrina; Kinkley, Sarah; Bürck, Carolin

2013-01-01

, and playing a role in DNA damage response. SPOC1 co-localized with viral replication centers in the host cell nucleus, interacted with Ad DNA, and repressed viral gene expression at the transcriptional level. We discovered that this SPOC1-mediated restriction imposed upon Ad growth is relieved by its...... viruses (HSV-1, HSV-2, HIV-1, and HCV) also depleted SPOC1 in infected cells. Our findings provide a general model for how pathogenic human viruses antagonize intrinsic SPOC1-mediated antiviral responses in their host cells. A better understanding of viral entry and early restrictive functions in host...

tRNA-dependent cysteine biosynthetic pathway represents a strategy to increase cysteine contents by preventing it from thermal degradation: thermal adaptation of methanogenic archaea ancestor.

Science.gov (United States)

Qu, Ge; Wang, Wei; Chen, Ling-Ling; Qian, Shao-Song; Zhang, Hong-Yu

2009-10-01

Although cysteine (Cys) is beneficial to stabilize protein structures, it is not prevalent in thermophiles. For instance, the Cys contents in most thermophilic archaea are only around 0.7%. However, methanogenic archaea, no matter thermophilic or not, contain relatively abundant Cys, which remains elusive for a long time. Recently, Klipcan et al. correlated this intriguing property of methanogenic archaea with their unique tRNA-dependent Cys biosynthetic pathway. But, the deep reasons underlying the correlation are ambiguous. Considering the facts that free Cys is thermally labile and the tRNA-dependent Cys biosynthesis avoids the use of free Cys, we speculate that the unique Cys biosynthetic pathway represents a strategy to increase Cys contents by preventing it from thermal degradation, which may be relevant to the thermal adaptation of methanogenic archaea ancestor.

A shared promoter region suggests a common ancestor for the human VCX/Y, SPANX, and CSAG gene families and the murine CYPT family

DEFF Research Database (Denmark)

Hansen, Martin A; Nielsen, John E; Retelska, Dorota

2008-01-01

, sequences corresponding to the shared promoter region of the CYPT family were identified at 39 loci. Most loci were located immediately upstream of genes belonging to the VCX/Y, SPANX, or CSAG gene families. Sequence comparison of the loci revealed a conserved CYPT promoter-like (CPL) element featuring TATA...... cell types. The genomic regions harboring the gene families were rich in direct and inverted segmental duplications (SD), which may facilitate gene conversion and rapid evolution. The conserved CPL and the common expression profiles suggest that the human VCX/Y, SPANX, and CSAG2 gene families together......Many testis-specific genes from the sex chromosomes are subject to rapid evolution, which can make it difficult to identify murine genes in the human genome. The murine CYPT gene family includes 15 members, but orthologs were undetectable in the human genome. However, using refined homology search...

Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation.

Science.gov (United States)

Suchorska, Wiktoria Maria; Augustyniak, Ewelina; Łukjanow, Magdalena

2017-04-01

Despite the well-demonstrated efficacy of stem cell (SC) therapy, this approach has a number of key drawbacks. One important concern is the response of pluripotent SCs to treatment with ionizing radiation (IR), given that SCs used in regenerative medicine will eventually be exposed to IR for diagnostic or treatment‑associated purposes. Therefore, the aim of the present study was to examine and compare early IR‑induced responses of pluripotent SCs to assess their radioresistance and radiosensitivity. In the present study, 3 cell lines; human embryonic SCs (hESCs), human induced pluripotent SCs (hiPSCs) and primary human dermal fibroblasts (PHDFs); were exposed to IR at doses ranging from 0 to 15 gray (Gy). Double strand breaks (DSBs), and the gene expression of the following DNA repair genes were analyzed: P53; RAD51; BRCA2; PRKDC; and XRCC4. hiPSCs demonstrated greater radioresistance, as fewer DSBs were identified, compared with hESCs. Both pluripotent SC lines exhibited distinct gene expression profiles in the most common DNA repair genes that are involved in homologous recombination, non‑homologous end‑joining and enhanced DNA damage response following IR exposure. Although hESCs and hiPSCs are equivalent in terms of capacity for pluripotency and differentiation into 3 germ layers, the results of the present study indicate that these 2 types of SCs differ in gene expression following exposure to IR. Consequently, further research is required to determine whether hiPSCs and hESCs are equally safe for application in clinical practice. The present study contributes to a greater understanding of DNA damage response (DDR) mechanisms activated in pluripotent SCs and may aid in the future development of safe SC‑based clinical protocols.

Lessons from Early Medicaid Expansions Under Health Reform..

Data.gov (United States)

U.S. Department of Health & Human Services — Lessons from Early Medicaid Expansions Under Health Reform, Interviews with Medicaid Officials In a new study entitled Lessons from Early Medicaid Expansions Under...

Christian Values in Vilhelm Kyukhelbekker's Early Prose

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Fedoseeva T.V.

2013-12-01

Full Text Available This article examines Vilhelm Kyukhelbekker's narrative prose of the first half of the 1820s. For the analysis we have chosen the most significant works of this period — his book of travel notes The Journey and the novel Ado. The study reveals the writer's attitude to Christianity and Christian values in his early period of work. In this research the axiological approach is used, as well as the methods of historical, typological, structural and semiotic study of literary texts. Studying The Journey, we performed a detailed analysis of the author's letters which describe the paintings by the artists of Flemish and Dutch schools, as well as German and Italian painters of the 17th and 18th centuries exhibited in the Dresden gallery. The writer prefers the paintings of biblical subjects to those of naturalistic everyday scenes. He pays special attention to the evangelical themes. He is attracted by Christ the child's divine nature and the heavenly purity, high humility of the Mother of God's image, and the fact that St. Sebastian is portrayed as joyfully suffering for Christ. Historical events of the novel Ado date back to the time of the Baltic peoples' forced Christianization by the Order of the Brothers of the Sword. Baltic peoples are trying to keep the faith of their ancestors and rebel against the cruel governor of the Order. The novel focuses particularly on one knight, Michael, who stood up for the oppressed and like Archangel Michael found himself on the cutting edge of Good and Evil. This character of the novel is connected with the idea of Christian sacrificial love and eternal spiritual life, which was very important for Kyukhelbekker. We concluded that even in his early prose Kyukhelbekker expressed the main spiritual and moral values of Christianity.

CHRISTIAN VALUES IN VILHELM KYUKHELBEKKER'S EARLY PROSE

Directory of Open Access Journals (Sweden)

Tatiana Vasilyevna Fedoseeva

2013-11-01

Full Text Available This article examines Vilhelm Kyukhelbekker's narrative prose of the first half of the 1820s. For the analysis we have chosen the most significant works of this period — his book of travel notes The Journey and the novel Ado. The study reveals the writer's attitude to Christianity and Christian values in his early period of work. In this research the axiological approach is used, as well as the methods of historical, typological, structural and semiotic study of literary texts. Studying The Journey, we performed a detailed analysis of the author's letters which describe the paintings by the artists of Flemish and Dutch schools, as well as German and Italian painters of the 17th and 18th centuries exhibited in the Dresden gallery. The writer prefers the paintings of biblical subjects to those of naturalistic everyday scenes. He pays special attention to the evangelical themes. He is attracted by Christ the child's divine nature and the heavenly purity, high humility of the Mother of God's image, and the fact that St. Sebastian is portrayed as joyfully suffering for Christ. Historical events of the novel Ado date back to the time of the Baltic peoples' forced Christianization by the Order of the Brothers of the Sword. Baltic peoples are trying to keep the faith of their ancestors and rebel against the cruel governor of the Order. The novel focuses particularly on one knight, Michael, who stood up for the oppressed and like Archangel Michael found himself on the cutting edge of Good and Evil. This character of the novel is connected with the idea of Christian sacrificial love and eternal spiritual life, which was very important for Kyukhelbekker. We concluded that even in his early prose Kyukhelbekker expressed the main spiritual and moral values of Christianity.

Recent advances in forest products research and development

Science.gov (United States)

Joseph E. Jakes

2016-01-01

Wood has always played an integral role in meeting our materials needs. The earliest evidence of woodworking dates back 1.5 million years to the modern human ancestor Homo erectus.1 Many characteristics that made wood a favorable material for our ancestors—relative abundance, ease of forming and shaping, exceptional strength-toweight ratio,...

Characterization of influenza A(H1N1)pdm09 viruses isolated from Nepalese and Indian outbreak patients in early 2015.

Science.gov (United States)

Nakamura, Kazuya; Shirakura, Masayuki; Fujisaki, Seiichiro; Kishida, Noriko; Burke, David F; Smith, Derek J; Kuwahara, Tomoko; Takashita, Emi; Takayama, Ikuyo; Nakauchi, Mina; Chadha, Mandeep; Potdar, Varsha; Bhushan, Arvind; Upadhyay, Bishnu Prasad; Shakya, Geeta; Odagiri, Takato; Kageyama, Tsutomu; Watanabe, Shinji

2017-09-01

We characterized influenza A(H1N1)pdm09 isolates from large-scale outbreaks that occurred in Nepal and India in early 2015. Although no specific viral features, which may have caused the outbreaks, were identified, an S84N substitution in hemagglutinin was frequently observed. Chronological phylogenetic analysis revealed that these Nepalese and Indian viruses possessing the S84N substitution constitute potential ancestors of the novel genetic subclade 6B.1 virus that spread globally in the following (2015/16) influenza season. Thus, active surveillance of circulating influenza viruses in the Southern Asia region, including Nepal and India, would be beneficial for detecting novel variant viruses prior to their worldwide spread. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Characterization and potential functional significance of human-chimpanzee large INDEL variation

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Polavarapu Nalini

2011-10-01

Full Text Available Abstract Background Although humans and chimpanzees have accumulated significant differences in a number of phenotypic traits since diverging from a common ancestor about six million years ago, their genomes are more than 98.5% identical at protein-coding loci. This modest degree of nucleotide divergence is not sufficient to explain the extensive phenotypic differences between the two species. It has been hypothesized that the genetic basis of the phenotypic differences lies at the level of gene regulation and is associated with the extensive insertion and deletion (INDEL variation between the two species. To test the hypothesis that large INDELs (80 to 12,000 bp may have contributed significantly to differences in gene regulation between the two species, we categorized human-chimpanzee INDEL variation mapping in or around genes and determined whether this variation is significantly correlated with previously determined differences in gene expression. Results Extensive, large INDEL variation exists between the human and chimpanzee genomes. This variation is primarily attributable to retrotransposon insertions within the human lineage. There is a significant correlation between differences in gene expression and large human-chimpanzee INDEL variation mapping in genes or in proximity to them. Conclusions The results presented herein are consistent with the hypothesis that large INDELs, particularly those associated with retrotransposons, have played a significant role in human-chimpanzee regulatory evolution.

Use of early phenotypic in vivo markers to assess human relevance of an unusual rodent non-genotoxic carcinogen in vitro

International Nuclear Information System (INIS)

Boess, Franziska; Lenz, Barbara; Funk, Juergen; Niederhauser, Urs; Bassett, Simon; Zhang, Jitao David; Singer, Thomas; Roth, Adrian B.

2017-01-01

Highlights: • RG3487 induced foci of altered hepatocytes and subsequent liver tumors in rats. • Early phenotypic markers preceding foci appearance in rats were identified. • These early foci markers could be recapitulated in cellular rat liver models. • A species comparison using rat, mouse and dog liver cell models qualified the approach. • In vitro human data support non-human-relevance for RG3487 induced foci formation. - Abstract: Foci of altered hepatocytes (FAH) are considered putative, pre-neoplastic lesions that can occur spontaneously in aging rodents, but can also be induced by chemicals or drugs. Progression of FAH to hepatocellular neoplasms has been reported repeatedly but increases in foci in rodents do not necessarily lead to tumors in carcinogenicity studies and the relevance for humans often remains unclear. Here we present the case of RG3487, a molecule which induced FAH and, later on, tumors in rats. Because the molecule was negative in genotoxicity assays it was classified as a non-genotoxic carcinogen. In order to assess the potential for liver tumor formation in humans, we analyzed treatment-induced changes in vivo to establish a possible mode of action (MoA). In vivo and in vitro gene expression analysis revealed that nuclear receptor signaling was unlikely to be the relevant MoA and no other known mechanism could be established. We therefore took an approach comparing phenotypic markers, including mRNA changes, proliferation and glycogen accumulation, in vitro using cells of different species to assess the human relevance of this finding. Since the alterations observed in rats were not seen in the liver of mice or dogs in vivo, we could validate the relevance of the cell models chosen by use of hepatocytes from these species in vitro. This ultimately allowed for a cross-species comparison, which suggested that the formation of FAH and liver tumors was rat specific and unlikely to translate to human. Our work showed that phenotypic

Immune Components in Human Milk Are Associated with Early Infant Immunological Health Outcomes: A Prospective Three-Country Analysis.

Science.gov (United States)

Munblit, Daniel; Treneva, Marina; Peroni, Diego G; Colicino, Silvia; Chow, Li Yan; Dissanayeke, Shobana; Pampura, Alexander; Boner, Attilio L; Geddes, Donna T; Boyle, Robert J; Warner, John O

2017-05-24

The role of breastfeeding in improving allergy outcomes in early childhood is still unclear. Evidence suggests that immune mediators in human milk (HM) play a critical role in infant immune maturation as well as protection against atopy/allergy development. We investigated relationships between levels of immune mediators in colostrum and mature milk and infant outcomes in the first year of life. In a large prospective study of 398 pregnant/lactating women in the United Kingdom, Russia and Italy, colostrum and mature human milk (HM) samples were analysed for immune active molecules. Statistical analyses used models adjusting for the site of collection, colostrum collection time, parity and maternal atopic status. Preliminary univariate analysis showed detectable interleukin (IL) 2 and IL13 in HM to be associated with less eczema. This finding was further confirmed in multivariate analysis, with detectable HM IL13 showing protective effect OR 0.18 (95% CI 0.04-0.92). In contrast, a higher risk of eczema was associated with higher HM concentrations of transforming growth factor β (TGFβ) 2 OR 1.04 (95% CI 1.01-1.06) per ng/mL. Parental-reported food allergy was reported less often when IL13 was detectable in colostrum OR 0.10 (95% CI 0.01-0.83). HM hepatocyte growth factor (HGF) was protective for common cold incidence at 12 months OR 0.19 (95% CI 0.04-0.92) per ng/mL. Data from this study suggests that differences in the individual immune composition of HM may have an influence on early life infant health outcomes. Increased TGFβ2 levels in HM are associated with a higher incidence of reported eczema, with detectable IL13 in colostrum showing protective effects for food allergy and sensitization. HGF shows some protective effect on common cold incidence at one year of age. Future studies should be focused on maternal genotype, human milk microbiome and diet influence on human milk immune composition and both short- and long-term health outcomes in the infant.

The Long Evolutionary Journey of Cancer from Ancestor to Modern Humans.

Science.gov (United States)

Carruba, Giuseppe; Trosko, James E

2017-01-01

In this article, we review various key issues in cancer development and progression that have important implications for both cancer prevention and treatment: (1) evolutionary aspects of cancer appearance; (2) evidence of organ-specific adult stem cells as cancer-initiating cells; (3) the immortality of cancer-initiating cells; (4) cancer cell loss of growth control, contact inhibition, terminal differentiation, and apoptosis; (5) stem-cell versus de-differentiation theory of carcinogenesis; (6) mutations in cancer; (7) oncogenes and tumor suppressor genes; (8) epigenetics as the rate-limiting step in carcinogenesis; (9) the potential role of cultural, lifestyle, and nutritional behaviors in oncology; and (10) changes of commensal microbial community and its metagenome in carcinogenesis and tumor progression. Relevant, combined evidence is discussed from a standpoint whereby cancer is considered a multifaceted disease requiring integrated biomolecular and clinico-pathological information to design and implement strategies for either primary prevention or therapy.

Early Pleistocene human hand phalanx from the Sima del Elefante (TE) cave site in Sierra de Atapuerca (Spain).

Science.gov (United States)

Lorenzo, Carlos; Pablos, Adrián; Carretero, José Miguel; Huguet, Rosa; Valverdú, Josep; Martinón-Torres, María; Arsuaga, Juan Luis; Carbonell, Eudald; Bermúdez de Castro, José María

2015-01-01

In this study, a new Early Pleistocene proximal hand phalanx (ATE9-2) from the Sima del Elefante cave site (TE - Sierra de Atapuerca, Spain), ascribed to Homo sp., is presented and comparatively described in the context of the evolution of the genus Homo. The ATE9-2 specimen is especially important because of the paucity of hand bones in the human fossil record during the Early Pleistocene. The morphological and metrical analyses of the phalanx ATE9-2 indicate that there are no essential differences between it and comparator fossil specimens for the genus Homo after 1.3 Ma (millions of years ago). Similar to Sima de los Huesos and Neandertal specimens, ATE9-2 is a robust proximal hand phalanx, probably reflecting greater overall body robusticity in these populations or a higher gracility in modern humans. The age of level TE9 from Sima del Elefante and morphological and metrical studies of ATE9-2 suggest that the morphology of the proximal hand phalanges and, thus, the morphology of the hand could have remained stable over the last 1.2-1.3 Ma. Taking into account the evidence recently provided by a metacarpal from Kaitio (Kenya) from around 1.42 Ma, we argue that modern hand morphology is present in the genus Homo subsequent to Homo habilis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Early detection of degraded A14-125I-insulin in human fibroblasts by the use of high performance liquid chromatography

International Nuclear Information System (INIS)

Stentz, F.B.; Harris, H.L.; Kitabchi, A.E.

1983-01-01

We studied the metabolism of A14-125I-insulin in intact human fibroblasts using high performance liquid chromatography (HPLC) to detect and separate its early degradation products. The high resolving power of HPLC enabled us to separate what has been considered ''intact insulin'' by Sephadex G-50 chromatography or TCA precipitability into two additional peaks that had decreased biochemical properties with respect to immunoprecipitability and receptor binding but not decreased TCA precipitability. We conclude that human fibroblast is capable of metabolizing insulin within 2 min at 37 degrees C into intermediate molecules that can be detected by HPLC but not by TCA precipitability or molecular sieve chromatography

Rethinking the theory of evolution: New perspectives on human evolution and why it matters for Theology

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J. Wentzel Van Huyssteen

2016-05-01

Full Text Available This article addresses the issue of human imagination from the perspective of ‘niche construction’ in the wider discussion about ‘what makes us human’ and what it means to be a ‘self’, specifically for the Christian faith and for theology. In the article, a brief review of human origins and human evolution demonstrates the path and substantive impact of changes in behaviour, life histories and bodies in our human ancestors and us as humans ourselves. In the interactive process of niche construction, potentially changeable natural environments were, and are, acting continuously on variation in the gene pools of populations, and in this way gene pools were modified over generations. It is argued that a distinctively human imagination is part of the explanation for human evolutionary success and can be seen as one of the structurally significant aspects of the transition from earlier members of the genus Homo to ourselves as we are today. There is thus a naturalness to human imagination, even to religious imagination, that facilitates engagement with the world that is truly distinct. This provides fruitful addition to the toolkit of inquiry for both evolutionary scientists and interdisciplinary theologians interested in reconstructing the long, winding historical path to humanity.

The medial pterygoid tubercle in the Atapuerca Early and Middle Pleistocene mandibles: evolutionary implications.

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Bermúdez de Castro, José-María; Quam, Rolf; Martinón-Torres, María; Martínez, Ignacio; Gracia-Téllez, Ana; Arsuaga, Juan Luís; Carbonell, Eudald

2015-01-01

Numerous studies have attempted to identify the presence of uniquely derived (autoapomorphic) Neandertal features. Here, we deal with the medial pterygoid tubercle (MTP), which is usually present on the internal face of the ascending ramus of Neandertal specimens. Our study stems from the identification of a hypertrophied tubercle in ATD6-96, an Early Pleistocene mandible recovered from the TD6 level of the Atapuerca-Gran Dolina site and attributed to Homo antecessor. Our review of the literature and study of numerous original fossil specimens and high quality replicas confirm that the MTP occurs at a high frequency in Neandertals (ca. 89%) and is also present in over half (ca. 55%) of the Middle Pleistocene Sima de los Huesos (SH) hominins. In contrast, it is generally absent or minimally developed in other extinct hominins, but can be found in variable frequencies (Early Pleistocene, and they should be interpreted as synapomorphies shared among different taxa. We suggest that H. antecessor, the SH hominins and Neandertals shared a common ancestor in which these features appeared during the Early Pleistocene. The presence of the MTP in taxa other than H. neanderthalensis precludes this feature from being a Neandertal autapomorphy. © 2014 Wiley Periodicals, Inc.

Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.

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Jonathan Göke

2011-12-01

Full Text Available Transcription factors are proteins that regulate gene expression by binding to cis-regulatory sequences such as promoters and enhancers. In embryonic stem (ES cells, binding of the transcription factors OCT4, SOX2 and NANOG is essential to maintain the capacity of the cells to differentiate into any cell type of the developing embryo. It is known that transcription factors interact to regulate gene expression. In this study we show that combinatorial binding is strongly associated with co-localization of the transcriptional co-activator Mediator, H3K27ac and increased expression of nearby genes in embryonic stem cells. We observe that the same loci bound by Oct4, Nanog and Sox2 in ES cells frequently drive expression in early embryonic development. Comparison of mouse and human ES cells shows that less than 5% of individual binding events for OCT4, SOX2 and NANOG are shared between species. In contrast, about 15% of combinatorial binding events and even between 53% and 63% of combinatorial binding events at enhancers active in early development are conserved. Our analysis suggests that the combination of OCT4, SOX2 and NANOG binding is critical for transcription in ES cells and likely plays an important role for embryogenesis by binding at conserved early developmental enhancers. Our data suggests that the fast evolutionary rewiring of regulatory networks mainly affects individual binding events, whereas "gene regulatory hotspots" which are bound by multiple factors and active in multiple tissues throughout early development are under stronger evolutionary constraints.

Six1 overexpression at early stages of HPV16-mediated transformation of human keratinocytes promotes differentiation resistance and EMT

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Xu, Hanwen; Pirisi, Lucia; Creek, Kim E.

2015-01-01

Previous studies in our laboratory discovered that SIX1 mRNA expression increased during in vitro progression of HPV16-immortalized human keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype. In this study, we explored the role of Six1 at early stages of HPV16-mediated transformation by overexpressing Six1 in HKc/HPV16. We found that Six1 overexpression in HKc/HPV16 increased cell proliferation and promoted cell migration and invasion by inducing epithelial–mesenchymal transition (EMT). Moreover, the overexpression of Six1 in HKc/HPV16 resulted in resistance to serum and calcium-induced differentiation, which is the hallmark of the HKc/DR phenotype. Activation of MAPK in HKc/HPV16 overexpressing Six1 is linked to resistance to calcium-induced differentiation. In conclusion, this study determined that Six1 overexpression resulted in differentiation resistance and promoted EMT at early stages of HPV16-mediated transformation of human keratinocytes. - Highlights: • Six1 expression increases during HPV16-mediated transformation. • Six1 overexpression causes differentiation resistance in HPV16-immortalized cells. • Six1 overexpression in HPV16-immortalized keratinocytes activates MAPK. • Activation of MAPK promotes EMT and differentiation resistance. • Six1 overexpression reduces Smad-dependent TGF-β signaling

Early human bone response to laser metal sintering surface topography: a histologic report.

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Mangano, Carlo; Piattelli, Adriano; d'Avila, Susana; Iezzi, Giovanna; Mangano, Francesco; Onuma, Tatiana; Shibli, Jamil Awad

2010-01-01

This histologic report evaluated the early human bone response to a direct laser metal sintering implant surface retrieved after a short period of healing. A selective laser sintering procedure using a Ti-6Al-4V alloy powder with a particle size of 25-45 microm prepared this surface topography. One experimental microimplant was inserted into the anterior mandible of a patient during conventional implant surgery of the jaw. The microimplant and surrounding tissues were removed after 2 months of unloaded healing and were prepared for histomorphometric analysis. Histologically, the peri-implant bone appeared in close contact with the implant surface, whereas marrow spaces could be detected in other areas along with prominently stained cement lines. The mean of bone-to-implant contact was 69.51%. The results of this histologic report suggest that the laser metal sintering surface could be a promising alternative to conventional implant surface topographies.

The Centre for Early Human Behaviour (EHB) at the University of Bergen: A transdisciplinary exploration into the evolution of homo sapiens behaviour

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Sobolowski, Stefan; Henshilwood, Christopher; Jansen, Eystein

2017-04-01

Homo sapiens was anatomically modern by 200 000 years ago in Africa, but there is no archaeological evidence to demonstrate that behaviour was modern at the time. Attributes of modern behaviour, perhaps inspired by changes in the human brain, are only recognizable after 100 000 years ago. Before we can study the process, we must critically define the criteria for the term 'modern behaviour' and then find a means to recognize such behavior in the record. This seemingly simple research statement involves complex exploration by a team of specialists. In this highly competitive research field our centre will, for the first time, be able to rise to the challenge by combining the skills of cutting-edge scientists in archaeology, climate reconstruction and modelling, and the cognitive and social sciences. Over the next decade we will integrate knowledge and methods from different disciplines to synthesize approaches and contribute to a sophisticated understanding of early human behaviour. Our highly ambitious research program will focus explicitly on rare, well preserved archaeological sites occupied in the period between 100-50 000 years ago because these contain the 'keys' for unlocking the past. A major competitive edge is the EHB Director's 25 years of archaeological experience and his long-term exclusive access, with permits, to a number of the best-preserved sites in the southern Cape, South Africa - a region regarded as a major locus for vital evidence that could inform on the behaviour of early humans. Our planned excavations at existing and new sites and our ground-breaking and innovative interdisciplinary approaches, including climate (The Bjerknes Centre for Climate Research) and cognitive research, to understanding the processes that shaped human cultures. Primarily, EHB will directly address unanswered, first order questions about Homo sapiens: a) what defines the switch to 'modern behaviour', exactly how should this term be defined and then, when, why and

Patterns of Early-Life Gut Microbial Colonization during Human Immune Development: An Ecological Perspective

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Isabelle Laforest-Lapointe

2017-07-01

Full Text Available Alterations in gut microbial colonization during early life have been reported in infants that later developed asthma, allergies, type 1 diabetes, as well as in inflammatory bowel disease patients, previous to disease flares. Mechanistic studies in animal models have established that microbial alterations influence disease pathogenesis via changes in immune system maturation. Strong evidence points to the presence of a window of opportunity in early life, during which changes in gut microbial colonization can result in immune dysregulation that predisposes susceptible hosts to disease. Although the ecological patterns of microbial succession in the first year of life have been partly defined in specific human cohorts, the taxonomic and functional features, and diversity thresholds that characterize these microbial alterations are, for the most part, unknown. In this review, we summarize the most important links between the temporal mosaics of gut microbial colonization and the age-dependent immune functions that rely on them. We also highlight the importance of applying ecology theory to design studies that explore the interactions between this complex ecosystem and the host immune system. Focusing research efforts on understanding the importance of temporally structured patterns of diversity, keystone groups, and inter-kingdom microbial interactions for ecosystem functions has great potential to enable the development of biologically sound interventions aimed at maintaining and/or improving immune system development and preventing disease.

The calmodulin-binding, short linear motif, NSCaTE is conserved in L-type channel ancestors of vertebrate Cav1.2 and Cav1.3 channels.

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Valentina Taiakina

Full Text Available NSCaTE is a short linear motif of (xWxxx(I or Lxxxx, composed of residues with a high helix-forming propensity within a mostly disordered N-terminus that is conserved in L-type calcium channels from protostome invertebrates to humans. NSCaTE is an optional, lower affinity and calcium-sensitive binding site for calmodulin (CaM which competes for CaM binding with a more ancient, C-terminal IQ domain on L-type channels. CaM bound to N- and C- terminal tails serve as dual detectors to changing intracellular Ca(2+ concentrations, promoting calcium-dependent inactivation of L-type calcium channels. NSCaTE is absent in some arthropod species, and is also lacking in vertebrate L-type isoforms, Cav1.1 and Cav1.4 channels. The pervasiveness of a methionine just downstream from NSCaTE suggests that L-type channels could generate alternative N-termini lacking NSCaTE through the choice of translational start sites. Long N-terminus with an NSCaTE motif in L-type calcium channel homolog LCav1 from pond snail Lymnaea stagnalis has a faster calcium-dependent inactivation than a shortened N-termini lacking NSCaTE. NSCaTE effects are present in low concentrations of internal buffer (0.5 mM EGTA, but disappears in high buffer conditions (10 mM EGTA. Snail and mammalian NSCaTE have an alpha-helical propensity upon binding Ca(2+-CaM and can saturate both CaM N-terminal and C-terminal domains in the absence of a competing IQ motif. NSCaTE evolved in ancestors of the first animals with internal organs for promoting a more rapid, calcium-sensitive inactivation of L-type channels.

Radioimmunoassay of an early plasmin degradation product of human fibrinogen, 'fragment A', and its clinical application

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Takagi, K; Kawai, T [Jichi Medical School, Kawachi, Tochigi (Japan)

1978-02-01

Upon the plasmin digestion of human fibrinogen, an early cleavage product, which has been designated as fragment A, was isolated, and to study the action of plasmin in the circulation, radioimmunoassay for fragment A was carried out. This assay used rabbit immune serum obtained by injection of fragment A mixed with complete Freund's adjuvant, and fragment A was labelled with /sup 125/I using the Chloramin-T method. In 20 normal healthy donors its serum level was 3.57 +- 1.62..mu..g/ml (mean+-SD), and it was increased significantly in certain diseases, such as acute leukemias, candiovascular disorders, malignancies, renal failure, systemic lupus erythematosus and sepsis.

Functional evolution of new and expanded attention networks in humans.

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Patel, Gaurav H; Yang, Danica; Jamerson, Emery C; Snyder, Lawrence H; Corbetta, Maurizio; Ferrera, Vincent P

2015-07-28

Macaques are often used as a model system for invasive investigations of the neural substrates of cognition. However, 25 million years of evolution separate humans and macaques from their last common ancestor, and this has likely substantially impacted the function of the cortical networks underlying cognitive processes, such as attention. We examined the homology of frontoparietal networks underlying attention by comparing functional MRI data from macaques and humans performing the same visual search task. Although there are broad similarities, we found fundamental differences between the species. First, humans have more dorsal attention network areas than macaques, indicating that in the course of evolution the human attention system has expanded compared with macaques. Second, potentially homologous areas in the dorsal attention network have markedly different biases toward representing the contralateral hemifield, indicating that the underlying neural architecture of these areas may differ in the most basic of properties, such as receptive field distribution. Third, despite clear evidence of the temporoparietal junction node of the ventral attention network in humans as elicited by this visual search task, we did not find functional evidence of a temporoparietal junction in macaques. None of these differences were the result of differences in training, experimental power, or anatomical variability between the two species. The results of this study indicate that macaque data should be applied to human models of cognition cautiously, and demonstrate how evolution may shape cortical networks.

Human Technology and Human Affects

DEFF Research Database (Denmark)

Fausing, Bent

2009-01-01

Human Technology and Human Affects  This year Samsung introduced a mobile phone with "Soul". It was made with a human touch and included itself a magical touch. Which function does technology and affects get in everyday aesthetics like this, its images and interactions included this presentation...... will ask and try to answer. The mobile phone and its devices are depicted as being able to make a unique human presence, interaction, and affect. The medium, the technology is a necessary helper to get towards this very special and lost humanity. Without the technology, no special humanity - soul....... The paper will investigate how technology, humanity, affects, and synaesthesia are presented and combined with examples from everyday aesthetics, e.g. early computer tv-commercial, net-commercial for mobile phones. Technology and affects point, is the conclusion, towards a forgotten pre-human and not he...

Universal biology and the statistical mechanics of early life

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Goldenfeld, Nigel; Biancalani, Tommaso; Jafarpour, Farshid

2017-11-01

All known life on the Earth exhibits at least two non-trivial common features: the canonical genetic code and biological homochirality, both of which emerged prior to the Last Universal Common Ancestor state. This article describes recent efforts to provide a narrative of this epoch using tools from statistical mechanics. During the emergence of self-replicating life far from equilibrium in a period of chemical evolution, minimal models of autocatalysis show that homochirality would have necessarily co-evolved along with the efficiency of early-life self-replicators. Dynamical system models of the evolution of the genetic code must explain its universality and its highly refined error-minimization properties. These have both been accounted for in a scenario where life arose from a collective, networked phase where there was no notion of species and perhaps even individuality itself. We show how this phase ultimately terminated during an event sometimes known as the Darwinian transition, leading to the present epoch of tree-like vertical descent of organismal lineages. These examples illustrate concrete examples of universal biology: the quest for a fundamental understanding of the basic properties of living systems, independent of precise instantiation in chemistry or other media. This article is part of the themed issue 'Reconceptualizing the origins of life'.

Distractor Effect of Auditory Rhythms on Self-Paced Tapping in Chimpanzees and Humans.

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Hattori, Yuko; Tomonaga, Masaki; Matsuzawa, Tetsuro

2015-01-01

Humans tend to spontaneously align their movements in response to visual (e.g., swinging pendulum) and auditory rhythms (e.g., hearing music while walking). Particularly in the case of the response to auditory rhythms, neuroscientific research has indicated that motor resources are also recruited while perceiving an auditory rhythm (or regular pulse), suggesting a tight link between the auditory and motor systems in the human brain. However, the evolutionary origin of spontaneous responses to auditory rhythms is unclear. Here, we report that chimpanzees and humans show a similar distractor effect in perceiving isochronous rhythms during rhythmic movement. We used isochronous auditory rhythms as distractor stimuli during self-paced alternate tapping of two keys of an electronic keyboard by humans and chimpanzees. When the tempo was similar to their spontaneous motor tempo, tapping onset was influenced by intermittent entrainment to auditory rhythms. Although this effect itself is not an advanced rhythmic ability such as dancing or singing, our results suggest that, to some extent, the biological foundation for spontaneous responses to auditory rhythms was already deeply rooted in the common ancestor of chimpanzees and humans, 6 million years ago. This also suggests the possibility of a common attentional mechanism, as proposed by the dynamic attending theory, underlying the effect of perceiving external rhythms on motor movement.

Characterization of migratory primordial germ cells in the aorta-gonad-mesonephros of a 4.5 week-old human embryo: a toolbox to evaluate in-vitro early gametogenesis.

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Gomes Fernandes, Maria; Bialecka, Monika; Salvatori, Daniela C F; Chuva de Sousa Lopes, Susana M

2018-03-08

Which set of antibodies can be used to identify migratory and early post-migratory human primordial germ cells (hPGCs)? We validated the specificity of 33 antibodies for 31 markers, including POU5F1, NANOG, PRDM1 and TFAP2C as specific markers of hPGCs at 4.5 weeks of development of Carnegie stage (CS12-13), whereas KIT and SOX17 also marked the intra-aortic hematopoietic stem cell cluster in the aorta-gonad-mesonephros (AGM). The dynamics of gene expression during germ cell development in mice is well characterized and this knowledge has proved crucial to allow the development of protocols for the in-vitro derivation of functional gametes. Although there is a great interest in generating human gametes in vitro, it is still unclear which markers are expressed during the early stages of hPGC development and many studies use markers described in mouse to benchmark differentiation of human PGC-like cells (hPGCLCs). Early post-implantation development differs significantly between mice and humans, and so some germ cells markers, including SOX2, SOX17, IFITM3 and ITGA6 may not identify mPGCs and hPGCs equally well. This immunofluorescence study investigated the expression of putative hPGC markers in the caudal part of a single human embryo at 4.5 weeks of development. We have investigated by immunofluorescence the expression of a set of 33 antibodies for 31 markers, including pluripotency, germ cell, adhesion, migration, surface, mesenchymal and epigenetic markers on paraffin sections of the caudal part, including the AGM region, of a single human embryo (CS 12-13). The human material used was anonymously donated with informed consent from elective abortions without medical indication. We observed germ cell specific expression of NANOG, TFAP2C and PRDM1 in POU5F1+ hPGCs in the AGM. The epigenetic markers H3K27me3 and 5mC were sufficient to distinguish hPGCs from the surrounding somatic cells. Some mPGC-markers were not detected in hPGCs, but marked other tissues

Improved analyses of human mtDNA sequences support a recent African origin for Homo sapiens.

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Penny, D; Steel, M; Waddell, P J; Hendy, M D

1995-09-01

New quantitative methods are applied to the 135 human mitochondrial sequences from the Vigilant et al. data set. General problems in analyzing large numbers of short sequences are discussed, and an improved strategy is suggested. A key feature is to focus not on individual trees but on the general "landscape" of trees. Over 1,000 searches were made from random starting trees with only one tree (a local optimum) being retained each time, thereby ensuring optima were found independently. A new tree comparison metric was developed that is unaffected by rearrangements of trees around many very short internal edges. Use of this metric showed that downweighting hypervariable sites revealed more evolutionary structure than studies that weighted all sites equally. Our results are consistent with convergence toward a global optimum. Crucial features are that the best optima show very strong regional differentiation, a common group of 49 African sequences is found in all the best optima, and the best optima contain the 16 !Kung sequences in a separate group of San people. The other 86 sequences form a heterogeneous mixture of Africans, Europeans, Australopapuans, and Asians. Thus all major human lineages occur in Africa, but only a subset occurs in the rest of the world. The existence of these African-only groups strongly contradicts multiregional theories for the origin of Homo sapiens that require widespread migration and interbreeding over the entire range of H. erectus. Only when the multiregional model is rejected is it appropriate to consider the root, based on a single locus, to be the center of origin of a population (otherwise different loci could give alternative geographic positions for the root). For this data, several methods locate the root within the group of 49 African sequences and are thus consistent with the recent African origin of H. sapiens. We demonstrate that the time of the last common ancestor cannot be the time of major expansion in human numbers

Supraorbital morphology and social dynamics in human evolution.

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Godinho, Ricardo Miguel; Spikins, Penny; O'Higgins, Paul

2018-04-09

Uniquely, with respect to Middle Pleistocene hominins, anatomically modern humans do not possess marked browridges, and have a more vertical forehead with mobile eyebrows that play a key role in social signalling and communication. The presence and variability of browridges in archaic Homo species and their absence in ourselves have led to debate concerning their morphogenesis and function, with two main hypotheses being put forward: that browridge morphology is the result of the spatial relationship between the orbits and the brain case; and that browridge morphology is significantly impacted by biting mechanics. Here, we virtually manipulate the browridge morphology of an archaic hominin (Kabwe 1), showing that it is much larger than the minimum required to fulfil spatial demands and that browridge size has little impact on mechanical performance during biting. As browridge morphology in this fossil is not driven by spatial and mechanical requirements alone, the role of the supraorbital region in social communication is a potentially significant factor. We propose that conversion of the large browridges of our immediate ancestors to a more vertical frontal bone in modern humans allowed highly mobile eyebrows to display subtle affiliative emotions.

Necessity of Aloha in Humanity s travels from the Earth

Science.gov (United States)

Yuen, D.

While technology and hardware provide the physical means to reach the Moon and beyond, the greatest explorers in human history took not only technologies, but a strong and guiding faith. This poster presentation seeks to present to the conference attendees the desirablility of using, as a m del for exploration, the Polynesiano voyaging culture, and most importantly, the concept of "Aloha" as a sound basis for interaction between humans of various cultures, and as a platform on which to base future exploration. The concept of "Aloha" is t h e c rnerstone of Hawaiian culture. It assures theo travelers' welcome, and it assures a safe departure. It is a haven in time of storm, and a fair wind along the journey. It is the food and drink of the soul. As we continue our explorations to new worlds, it is paramount that we continue the tradition of Aloha. The ancestors of the Hawaiians were adventurers, explorers, and settlers. Not knowing if they would be able to return to the homeland, they took with them the necessities of their lives - pigs, chickens, dogs, taro, sweet potato, breadfruit, gourds - and many other things they knew to be useful. And they took Aloha. We also must take with us food and tools, though in different forms than the early explorers. And, we also must take Aloha. Aloha is similar in concept to Namaste, a Sanskrit greeting which can be translated as "the divine in me honors the divine in you." It is far more rich in meaning than can be expressed in a Visitors' Bureau phrasebook. While Aloha is translated as, "hello," "goodby," "love," "affection," and "friendship," it also embodies responsibility for oneself and for one's actions toward others. It is a verbal shorthand which expresses an acknowledgement of the net-like interweaving of family and community relationships. In the twenty first century we can look to the example of these successful explorers. We, too, can carry with us an inexhaustible supply of Aloha. It has no mass, no height, depth

Aspect of the early human occupation in Uruguay

International Nuclear Information System (INIS)

Castineira, C.

2012-01-01

This work is about the studies carried out in the geological sedimentary formation called So pa which is located in the basaltic basin in the north of Uruguay. The results obtained allow to recognize characteristics of the late pleistocene - early holocene as well as geometric morpho metrics aspects

Evolutionary origins and early development of number processing

CERN Document Server

Geary, David C; Mann Koepke, Kathleen

2014-01-01

The first volume in this ground-breaking series focuses on the origins and early development of numerical cognition in non-human primates, lower vertebrates, human infants, and preschool children. The text will help readers understand the nature and complexity of these foundational quantitative concepts and skills along with evolutionary precursors and early developmental trajectories. Brings together and focuses the efforts and research of multiple disciplines working in math cognition.The contributors bring vast knowledge and experience to bear on resolving extant

Evolution from a respiratory ancestor to fill syntrophic and fermentative niches: comparative fenomics of six Geobacteraceae species

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Lovley Derek R

2009-03-01

Full Text Available Abstract Background The anaerobic degradation of organic matter in natural environments, and the biotechnical use of anaerobes in energy production and remediation of subsurface environments, both require the cooperative activity of a diversity of microorganisms in different metabolic niches. The Geobacteraceae family contains members with three important anaerobic metabolisms: fermentation, syntrophic degradation of fermentation intermediates, and anaerobic respiration. Results In order to learn more about the evolution of anaerobic microbial communities, the genome sequences of six Geobacteraceae species were analyzed. The results indicate that the last common Geobacteraceae ancestor contained sufficient genes for anaerobic respiration, completely oxidizing organic compounds with the reduction of external electron acceptors, features that are still retained in modern Geobacter and Desulfuromonas species. Evolution of specialization for fermentative growth arose twice, via distinct lateral gene transfer events, in Pelobacter carbinolicus and Pelobacter propionicus. Furthermore, P. carbinolicus gained hydrogenase genes and genes for ferredoxin reduction that appear to permit syntrophic growth via hydrogen production. The gain of new physiological capabilities in the Pelobacter species were accompanied by the loss of several key genes necessary for the complete oxidation of organic compounds and the genes for the c-type cytochromes required for extracellular electron transfer. Conclusion The results suggest that Pelobacter species evolved parallel strategies to enhance their ability to compete in environments in which electron acceptors for anaerobic respiration were limiting. More generally, these results demonstrate how relatively few gene changes can dramatically transform metabolic capabilities and expand the range of environments in which microorganisms can compete.

Prospective assessment of early fetal loss using an immunoenzymometric screening assay for detection of urinary human chorionic gonadotropin.

Science.gov (United States)

Taylor, C A; Overstreet, J W; Samuels, S J; Boyers, S P; Canfield, R E; O'Connor, J F; Hanson, F W; Lasley, B L

1992-06-01

To develop an economical, nonradiometric immunoenzymometric assay (IEMA) for the detection of urinary human chorionic gonadotropin (hCG) in studies of early fetal loss. To be effective, the IEMA must have a sensitivity equal to the standard immunoradiometric assay (IRMA) and sufficient specificity to eliminate the need for screening most nonconceptive cycles with the expensive and labor-intensive IRMA. Two different assays were used to measure hCG in daily early morning urine samples from potential conceptive cycles. Women undergoing donor artificial insemination (AI) were evaluated in a prospective study. Ninety-two women volunteers were selected on the basis of apparent normal reproductive health. Artificial insemination with nonfrozen donor semen was performed by cervical cup twice each menstrual cycle at 48-hour intervals, and daily urine samples were self-collected throughout the menstrual cycle. An IEMA was developed to detect urinary hCG using the same antibodies as in the standard IRMA; a study was designed to determine whether this nonradiometric assay could successfully detect the early fetal loss that was detected by the IRMA. Of 224 menstrual cycles analyzed by both assays, a total of six early fetal losses were detected by the IRMA. When the tentative screening rule was set to allow all six of these losses and 95% of future losses to be detected by the IEMA, an additional 34 false-positive results were detected by the IEMA. The specificity of the IEMA with this rule was calculated to be 84%. An IEMA based on the same antibodies used for the standard IRMA can serve as an efficient screening assay for the detection of early fetal loss. When the IEMA is used in this manner, nearly 80% of screened menstrual cycles can be eliminated without further testing by the IRMA.

Comparative Analysis of Gene Expression for Convergent Evolution of Camera Eye Between Octopus and Human

Science.gov (United States)

Ogura, Atsushi; Ikeo, Kazuho; Gojobori, Takashi

2004-01-01

Although the camera eye of the octopus is very similar to that of humans, phylogenetic and embryological analyses have suggested that their camera eyes have been acquired independently. It has been known as a typical example of convergent evolution. To study the molecular basis of convergent evolution of camera eyes, we conducted a comparative analysis of gene expression in octopus and human camera eyes. We sequenced 16,432 ESTs of the octopus eye, leading to 1052 nonredundant genes that have matches in the protein database. Comparing these 1052 genes with 13,303 already-known ESTs of the human eye, 729 (69.3%) genes were commonly expressed between the human and octopus eyes. On the contrary, when we compared octopus eye ESTs with human connective tissue ESTs, the expression similarity was quite low. To trace the evolutionary changes that are potentially responsible for camera eye formation, we also compared octopus-eye ESTs with the completed genome sequences of other organisms. We found that 1019 out of the 1052 genes had already existed at the common ancestor of bilateria, and 875 genes were conserved between humans and octopuses. It suggests that a larger number of conserved genes and their similar gene expression may be responsible for the convergent evolution of the camera eye. PMID:15289475

[Pathology of amniogenesis in the early prenatal period of human development].

Science.gov (United States)

Kulazhenko, V P; Bragina, Z N

1989-08-01

Morphological and, in a number of cases, cytogenetical investigation has been performed in 420 intact embryonal sacs and in embryos 7-8-week-old, obtained at spontaneous abortions (272) and at tubal pregnancy (148). Among these cases 202 (48.1%) intact empty embryonal sacs, 75 (17.9%) embryos with panorganodysplasia, 25 (6%) embryos with isolated developmental defects and 118 (28%) phenotypically normal embryos have been revealed. Pathology of amniogenesis such as aplasia or hypoplasia of the amniotic cavity is noted in 136 (32.4%) cases. Among 75 embryos with panorganodysplasia anomalies such as hypoplasia of the amniotic cavity in combination with a partial extra-amniotic++ position of the embryos in exocelom (10.7%), aplasia (5.3%) or hypoplasia (17.3%) amniotic peduncle is present in 43 (57.3%) observations. Out of 40 such cases at spontaneous abortions, cytogenetically investigated, in 27 (67.5%) chromosomal disorders (tetraploidy, triploidy, autosomal trisomy and monosomy) are revealed. Aplasia and hypoplasia of the amniotic cavity are considered as pathology of histogenesis at the tissue stage of the early human ontogenesis, that most evidently occurs as a result of asplasia, destruction or anomaly of embryoblast during the first phase of gastrulation on the 7th-11th day of the intrauterine development.

Human heart-type fatty acid-binding protein as an early diagnostic marker of doxorubicin cardiac toxicity

Directory of Open Access Journals (Sweden)

Ashraf H. ElGhandour

2009-04-01

Full Text Available Progressive cardiotoxicity following treatment with doxorubicin-based chemotherapy in patients with non-Hodgkin’s lymphoma (NHL may lead to late onset cardiomyopathy. So, early prediction of toxicity can lead to prevention of heart failure in these patients. The aim of this work was to investigate the role of H-FABP as an early diagnostic marker of anthracycline-induced cardiac toxicity together with brain natriuretic peptide (BNP as an indication of ventricular dysfunction in such patients. Our study was conducted on 40 NHL patients who received 6 cycles of a doxorubicin containing chemotherapy protocol (CHOP, not exceeding the total allowed dose of doxorubicin (500 mg/m2. Ten healthy controls were included in our study. Human heart-type fatty acid binding protein (H-FABP was assessed 24 hours after the first cycle of CHOP. Plasma levels of BNP were estimated both before starting chemotherapy and after the last cycle of CHOP. Resting echocardiography was also performed before and at the end of chemotherapy cycles. The ejection fraction (EF of 8 of our patients decreased below 50% at the end of the sixth cycle. Elevated levels of both H-FABP and BNP were found in all patients wth EF below 50% and both markers showed a positive correlation with each other. We concluded that H-FABP may serve as a reliable early marker for prediction of cardiomyopathy induced by doxorubicin. Thus, in patients with elevated H-FABP, alternative treatment modalities with no cardiac toxicity may be considered in order to prevent subsequent heart failure in these patients.

Early Retiree Reinsurance Program Reports

Data.gov (United States)

U.S. Department of Health & Human Services — The Early Retiree Reinsurance Program (ERRP) was established by section 1102 of the Patient Protection and Affordable Care Act (the Affordable Care Act) enacted on...

Abnormal early cleavage events predict early embryo demise: sperm oxidative stress and early abnormal cleavage.

Science.gov (United States)

Burruel, Victoria; Klooster, Katie; Barker, Christopher M; Pera, Renee Reijo; Meyers, Stuart

2014-10-13

Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors.

Physical mapping of a large plant genome using global high-information-content-fingerprinting: the distal region of the wheat ancestor Aegilops tauschii chromosome 3DS

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You Frank M

2010-06-01

Full Text Available Abstract Background Physical maps employing libraries of bacterial artificial chromosome (BAC clones are essential for comparative genomics and sequencing of large and repetitive genomes such as those of the hexaploid bread wheat. The diploid ancestor of the D-genome of hexaploid wheat (Triticum aestivum, Aegilops tauschii, is used as a resource for wheat genomics. The barley diploid genome also provides a good model for the Triticeae and T. aestivum since it is only slightly larger than the ancestor wheat D genome. Gene co-linearity between the grasses can be exploited by extrapolating from rice and Brachypodium distachyon to Ae. tauschii or barley, and then to wheat. Results We report the use of Ae. tauschii for the construction of the physical map of a large distal region of chromosome arm 3DS. A physical map of 25.4 Mb was constructed by anchoring BAC clones of Ae. tauschii with 85 EST on the Ae. tauschii and barley genetic maps. The 24 contigs were aligned to the rice and B. distachyon genomic sequences and a high density SNP genetic map of barley. As expected, the mapped region is highly collinear to the orthologous chromosome 1 in rice, chromosome 2 in B. distachyon and chromosome 3H in barley. However, the chromosome scale of the comparative maps presented provides new insights into grass genome organization. The disruptions of the Ae. tauschii-rice and Ae. tauschii-Brachypodium syntenies were identical. We observed chromosomal rearrangements between Ae. tauschii and barley. The comparison of Ae. tauschii physical and genetic maps showed that the recombination rate across the region dropped from 2.19 cM/Mb in the distal region to 0.09 cM/Mb in the proximal region. The size of the gaps between contigs was evaluated by comparing the recombination rate along the map with the local recombination rates calculated on single contigs. Conclusions The physical map reported here is the first physical map using fingerprinting of a complete

Identification, genealogical structure and population genetics of S-alleles in Malus sieversii, the wild ancestor of domesticated apple.

Science.gov (United States)

Ma, X; Cai, Z; Liu, W; Ge, S; Tang, L

2017-09-01

The self-incompatibility (SI) gene that is specifically expressed in pistils encodes the SI-associated ribonuclease (S-RNase), functioning as the female-specificity determinant of a gametophytic SI system. Despite extensive surveys in Malus domestica, the S-alleles have not been fully investigated for Malus sieversii, the primary wild ancestor of the domesticated apple. Here we screened the M. sieversii S-alleles via PCR amplification and sequencing, and identified 14 distinct alleles in this species. By contrast, nearly 40 are present in its close wild relative, Malus sylvestris. We further sequenced 8 nuclear genes to provide a neutral reference, and investigated the evolution of S-alleles via genealogical and population genetic analyses. Both shared ancestral polymorphism and an excess of non-synonymous substitution were detected in the S-RNases of the tribe Maleae in Rosaceae, indicating the action of long-term balancing selection. Approximate Bayesian Computations based on the reference neutral loci revealed a severe bottleneck in four of the six studied M. sieversii populations, suggesting that the low number of S-alleles found in this species is mainly the result of diversity loss due to a drastic population contraction. Such a bottleneck may lead to ambiguous footprints of ongoing balancing selection detected at the S-locus. This study not only elucidates the constituents and number of S-alleles in M. sieversii but also illustrates the potential utility of S-allele number shifts in demographic inference for self-incompatible plant species.

Additions, losses, and rearrangements on the evolutionary route from a reconstructed ancestor to the modern Saccharomyces cerevisiae genome.

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Jonathan L Gordon

2009-05-01

Full Text Available Comparative genomics can be used to infer the history of genomic rearrangements that occurred during the evolution of a species. We used the principle of parsimony, applied to aligned synteny blocks from 11 yeast species, to infer the gene content and gene order that existed in the genome of an extinct ancestral yeast about 100 Mya, immediately before it underwent whole-genome duplication (WGD. The reconstructed ancestral genome contains 4,703 ordered loci on eight chromosomes. The reconstruction is complete except for the subtelomeric regions. We then inferred the series of rearrangement steps that led from this ancestor to the current Saccharomyces cerevisiae genome; relative to the ancestral genome we observe 73 inversions, 66 reciprocal translocations, and five translocations involving telomeres. Some fragile chromosomal sites were reused as evolutionary breakpoints multiple times. We identified 124 genes that have been gained by S. cerevisiae in the time since the WGD, including one that is derived from a hAT family transposon, and 88 ancestral loci at which S. cerevisiae did not retain either of the gene copies that were formed by WGD. Sites of gene gain and evolutionary breakpoints both tend to be associated with tRNA genes and, to a lesser extent, with origins of replication. Many of the gained genes in S. cerevisiae have functions associated with ethanol production, growth in hypoxic environments, or the uptake of alternative nutrient sources.

Visitors views of human origins after visiting the Cradle of Humankind World Heritage Site

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Anthony Lelliott

2016-02-01

Full Text Available The Cradle of Humankind World Heritage Site, west of Johannesburg, was designated in 1999 because of its importance as a locality where numerous hominid fossils have been discovered since the 1930s. In this article, responses to questions from a survey of more than 800 adult visitors to the Cradle of Humankind visitor centres are analysed, covering their understanding of the concept of the "cradle" and their views on human evolution. Findings indicated that 63% of the respondents conceptualised the cradle as the origin or birthplace of humankind, and a similar proportion thought that nowhere else could be called the Cradle of Humankind (77% of people of South African nationality thought this. Nearly 60% of respondents accepted that humans evolved from an ape-like ancestor, while 25% disagreed. South Africans were less likely to accept human evolution than their international counterparts. The great majority of participants who accepted human evolution based their agreement on various forms of evidence and their knowledge of evolution. A religious foundation was used for their rationale by 60% of those who rejected evolution, with 33% citing evidence for their rejection. The implications of the findings are discussed in the light of public awareness and human origins.

Unique genome organization of non-mammalian papillomaviruses provides insights into the evolution of viral early proteins.

Science.gov (United States)

Van Doorslaer, Koenraad; Ruoppolo, Valeria; Schmidt, Annie; Lescroël, Amelie; Jongsomjit, Dennis; Elrod, Megan; Kraberger, Simona; Stainton, Daisy; Dugger, Katie M; Ballard, Grant; Ainley, David G; Varsani, Arvind

2017-07-01

The family Papillomaviridae contains more than 320 papillomavirus types, with most having been identified as infecting skin and mucosal epithelium in mammalian hosts. To date, only nine non-mammalian papillomaviruses have been described from birds ( n  = 5), a fish ( n  = 1), a snake ( n  = 1), and turtles ( n  = 2). The identification of papillomaviruses in sauropsids and a sparid fish suggests that early ancestors of papillomaviruses were already infecting the earliest Euteleostomi. The Euteleostomi clade includes more than 90 per cent of the living vertebrate species, and progeny virus could have been passed on to all members of this clade, inhabiting virtually every habitat on the planet. As part of this study, we isolated a novel papillomavirus from a 16-year-old female Adélie penguin ( Pygoscelis adeliae ) from Cape Crozier, Ross Island (Antarctica). The new papillomavirus shares ∼64 per cent genome-wide identity to a previously described Adélie penguin papillomavirus. Phylogenetic analyses show that the non-mammalian viruses (expect the python, Morelia spilota , associated papillomavirus) cluster near the base of the papillomavirus evolutionary tree. A papillomavirus isolated from an avian host (Northern fulmar; Fulmarus glacialis ), like the two turtle papillomaviruses, lacks a putative E9 protein that is found in all other avian papillomaviruses. Furthermore, the Northern fulmar papillomavirus has an E7 more similar to the mammalian viruses than the other avian papillomaviruses. Typical E6 proteins of mammalian papillomaviruses have two Zinc finger motifs, whereas the sauropsid papillomaviruses only have one such motif. Furthermore, this motif is absent in the fish papillomavirus. Thus, it is highly likely that the most recent common ancestor of the mammalian and sauropsid papillomaviruses had a single motif E6. It appears that a motif duplication resulted in mammalian papillomaviruses having a double Zinc finger motif in E6. We

Unique genome organization of non-mammalian papillomaviruses provides insights into the evolution of viral early proteins

Science.gov (United States)

Van Doorslaer, Koenraad; Ruoppolo, Valeria; Schmidt, Annie; Lescroël, Amelie; Jongsomjit, Dennis; Elrod, Megan; Kraberger, Simona; Stainton, Daisy; Dugger, Katie M.; Ballard, Grant; Ainley, David G.; Varsani, Arvind

2017-01-01

The family Papillomaviridae contains more than 320 papillomavirus types, with most having been identified as infecting skin and mucosal epithelium in mammalian hosts. To date, only nine non-mammalian papillomaviruses have been described from birds (n = 5), a fish (n = 1), a snake (n = 1), and turtles (n = 2). The identification of papillomaviruses in sauropsids and a sparid fish suggests that early ancestors of papillomaviruses were already infecting the earliest Euteleostomi. The Euteleostomi clade includes more than 90 per cent of the living vertebrate species, and progeny virus could have been passed on to all members of this clade, inhabiting virtually every habitat on the planet. As part of this study, we isolated a novel papillomavirus from a 16-year-old female Adélie penguin (Pygoscelis adeliae) from Cape Crozier, Ross Island (Antarctica). The new papillomavirus shares ∼64 per cent genome-wide identity to a previously described Adélie penguin papillomavirus. Phylogenetic analyses show that the non-mammalian viruses (expect the python, Morelia spilota, associated papillomavirus) cluster near the base of the papillomavirus evolutionary tree. A papillomavirus isolated from an avian host (Northern fulmar; Fulmarus glacialis), like the two turtle papillomaviruses, lacks a putative E9 protein that is found in all other avian papillomaviruses. Furthermore, the Northern fulmar papillomavirus has an E7 more similar to the mammalian viruses than the other avian papillomaviruses. Typical E6 proteins of mammalian papillomaviruses have two Zinc finger motifs, whereas the sauropsid papillomaviruses only have one such motif. Furthermore, this motif is absent in the fish papillomavirus. Thus, it is highly likely that the most recent common ancestor of the mammalian and sauropsid papillomaviruses had a single motif E6. It appears that a motif duplication resulted in mammalian papillomaviruses having a double Zinc finger motif in E6. We estimated the

OH 83: A new early modern human fossil cranium from the Ndutu beds of Olduvai Gorge, Tanzania.

Science.gov (United States)

Reiner, Whitney B; Masao, Fidelis; Sholts, Sabrina B; Songita, Agustino Venance; Stanistreet, Ian; Stollhofen, Harald; Taylor, R E; Hlusko, Leslea J

2017-11-01

Herein we introduce a newly recovered partial calvaria, OH 83, from the upper Ndutu Beds of Olduvai Gorge, Tanzania. We present the geological context of its discovery and a comparative analysis of its morphology, placing OH 83 within the context of our current understanding of the origins and evolution of Homo sapiens. We comparatively assessed the morphology of OH 83 using quantitative and qualitative data from penecontemporaneous fossils and the W.W. Howells modern human craniometric dataset. OH 83 is geologically dated to ca. 60-32 ka. Its morphology is indicative of an early modern human, falling at the low end of the range of variation for post-orbital cranial breadth, the high end of the range for bifrontal breadth, and near average in frontal length. There have been numerous attempts to use cranial anatomy to define the species Homo sapiens and identify it in the fossil record. These efforts have not met wide agreement by the scientific community due, in part, to the mosaic patterns of cranial variation represented by the fossils. The variable, mosaic pattern of trait expression in the crania of Middle and Late Pleistocene fossils implies that morphological modernity did not occur at once. However, OH 83 demonstrates that by ca. 60-32 ka modern humans in Africa included individuals that are at the fairly small and gracile range of modern human cranial variation. © 2017 Wiley Periodicals, Inc.

Digging for the human mind cognitive archaeology and the origins of science, art and religion

CERN Multimedia

Mithen, S

1999-01-01

Understanding the nature of the human mind is one of the greatest challenges faced by science, and one which requires the participation of many disciplines. During the last decade there have been strong arguments that an evolutionary perspective on the mind is required Ñ just like any other species humans are the products of biological evolution and this will have moulded the way we think as much as the way we walk and talk. Some evolutionary psychologists go so far as to argue that the way we think remains largely conditioned by the lifestyle of our prehistoric hunter-gatherer ancestors. While there is both logic and substantial evidence for this claim, it fails to account for many of the activities of modern humans which have no evolutionary precedent or even the faintest trace in our closest living relative, the great apes. Notably among these are the pursuit of pure science, art and religion Ñ activities that appear to lack any functional value. In my paper I will suggest how these can indeed be account...

A molecular clock dates the common ancestor of European-type porcine reproductive and respiratory syndrome virus at more than 10 years before the emergence of disease

DEFF Research Database (Denmark)

Forsberg, Roald; Oleksiewicz, Martin B.; Krabbe Petersen, Anne Mette

2001-01-01

an accurate molecular clock for the European PRRSV ORF 3 gene, place the root in the genealogy, estimate the rate of nucleotide substitution, and date the most recent common viral ancestor of the data set to 1979; more than 10 years before the onset of the European epidemic. Based on these findings, we...... conclude that PRRSV virus most likely entered the pig population some time before the epidemic emergence of the virus, and hence, that emergence of European-type PRRSV is not the result of a recent species transmission event. Together, our results show that ORF3 sequencing is a valuable epidemiologic tool...... for examining the emergence and spread of PRRSV in Europe. As such, the panel of well-characterized and highly divergent ORF3 sequences described in this study provides a reference point for future molecular epidemiologic studies....

Primate vocal communication: a useful tool for understanding human speech and language evolution?

Science.gov (United States)

Fedurek, Pawel; Slocombe, Katie E

2011-04-01

Language is a uniquely human trait, and questions of how and why it evolved have been intriguing scientists for years. Nonhuman primates (primates) are our closest living relatives, and their behavior can be used to estimate the capacities of our extinct ancestors. As humans and many primate species rely on vocalizations as their primary mode of communication, the vocal behavior of primates has been an obvious target for studies investigating the evolutionary roots of human speech and language. By studying the similarities and differences between human and primate vocalizations, comparative research has the potential to clarify the evolutionary processes that shaped human speech and language. This review examines some of the seminal and recent studies that contribute to our knowledge regarding the link between primate calls and human language and speech. We focus on three main aspects of primate vocal behavior: functional reference, call combinations, and vocal learning. Studies in these areas indicate that despite important differences, primate vocal communication exhibits some key features characterizing human language. They also indicate, however, that some critical aspects of speech, such as vocal plasticity, are not shared with our primate cousins. We conclude that comparative research on primate vocal behavior is a very promising tool for deepening our understanding of the evolution of human speech and language, but much is still to be done as many aspects of monkey and ape vocalizations remain largely unexplored.

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

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Rachel Sarig

Full Text Available 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.

What can we infer about the origin of sex in early eukaryotes?

NARCIS (Netherlands)

Speijer, Dave

2016-01-01

Current analysis shows that the last eukaryotic common ancestor (LECA) was capable of full meiotic sex. The original eukaryotic life cycle can probably be described as clonal, interrupted by episodic sex triggered by external or internal stressors. The cycle could have started in a highly flexible

Alterations in human milk leptin and insulin are associated with early changes in the infant intestinal microbiome.

Science.gov (United States)

Lemas, Dominick J; Young, Bridget E; Baker, Peter R; Tomczik, Angela C; Soderborg, Taylor K; Hernandez, Teri L; de la Houssaye, Becky A; Robertson, Charles E; Rudolph, Michael C; Ir, Diana; Patinkin, Zachary W; Krebs, Nancy F; Santorico, Stephanie A; Weir, Tiffany; Barbour, Linda A; Frank, Daniel N; Friedman, Jacob E

2016-05-01

Increased maternal body mass index (BMI) is a robust risk factor for later pediatric obesity. Accumulating evidence suggests that human milk (HM) may attenuate the transfer of obesity from mother to offspring, potentially through its effects on early development of the infant microbiome. Our objective was to identify early differences in intestinal microbiota in a cohort of breastfeeding infants born to obese compared with normal-weight (NW) mothers. We also investigated relations between HM hormones (leptin and insulin) and both the taxonomic and functional potentials of the infant microbiome. Clinical data and infant stool and fasting HM samples were collected from 18 NW [prepregnancy BMI (in kg/m(2)) obese (prepregnancy BMI >30.0) mothers and their exclusively breastfed infants at 2 wk postpartum. Infant body composition at 2 wk was determined by air-displacement plethysmography. Infant gastrointestinal microbes were estimated by using 16S amplicon and whole-genome sequencing. HM insulin and leptin were determined by ELISA; short-chain fatty acids (SCFAs) were measured in stool samples by using gas chromatography. Power was set at 80%. Infants born to obese mothers were exposed to 2-fold higher HM insulin and leptin concentrations (P obesity may adversely affect the early infant intestinal microbiome, HM insulin and leptin are independently associated with beneficial microbial metabolic pathways predicted to increase intestinal barrier function and reduce intestinal inflammation. This trial was registered at clinicaltrials.gov as NCT01693406. © 2016 American Society for Nutrition.

Major genomic mitochondrial lineages delineate early human expansions

Directory of Open Access Journals (Sweden)

Flores Carlos

2001-08-01

Full Text Available Abstract Background The phylogeographic distribution of human mitochondrial DNA variations allows a genetic approach to the study of modern Homo sapiens dispersals throughout the world from a female perspective. As a new contribution to this study we have phylogenetically analysed complete mitochondrial DNA(mtDNA sequences from 42 human lineages, representing major clades with known geographic assignation. Results We show the relative relationships among the 42 lineages and present more accurate temporal calibrations than have been previously possible to give new perspectives as how modern humans spread in the Old World. Conclusions The first detectable expansion occurred around 59,000–69,000 years ago from Africa, independently colonizing western Asia and India and, following this southern route, swiftly reaching east Asia. Within Africa, this expansion did not replace but mixed with older lineages detectable today only in Africa. Around 39,000–52,000 years ago, the western Asian branch spread radially, bringing Caucasians to North Africa and Europe, also reaching India, and expanding to north and east Asia. More recent migrations have entangled but not completely erased these primitive footprints of modern human expansions.

Hypothesis: brain size and skull shape as criteria for a new hominin family tree.

Science.gov (United States)

Chardin, Pierre

2014-10-01

Today, gorillas and chimpanzees live in tropical forests, where acid soils do not favor fossilization. It is thus widely believed that there are no fossils of chimpanzees or gorillas. However, four teeth of a 0.5-million-year (Ma)-old chimpanzee were discovered in the rift valley of Kenya (McBrearty and Jablonski, 2005), and a handful of teeth of a 10-Ma-old gorilla-like creature were found in Ethiopia (Suwa et al., 2007), close to the major sites of Homo discoveries. These discoveries indicate that chimpanzees and gorillas once shared their range with early Homo. However, the thousands of hominin fossils discovered in the past century have all been attributed to the Homo line. Thus far, our family tree looks like a bush with many dead-branches. If one admits the possibility that the australopithecines can also be the ancestors of African great apes, one can place Paranthropus on the side of gorilla ancestors and divide the remaining Australopithecus based on the brain size into the two main lines of humans and chimpanzees, thereby resulting in a coherent family tree. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

Science.gov (United States)

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.

Who ate whom? Adaptive Helicobacter genomic changes that accompanied a host jump from early humans to large felines.

Directory of Open Access Journals (Sweden)

Mark Eppinger

2006-07-01

Full Text Available Helicobacter pylori infection of humans is so old that its population genetic structure reflects that of ancient human migrations. A closely related species, Helicobacter acinonychis, is specific for large felines, including cheetahs, lions, and tigers, whereas hosts more closely related to humans harbor more distantly related Helicobacter species. This observation suggests a jump between host species. But who ate whom and when did it happen? In order to resolve this question, we determined the genomic sequence of H. acinonychis strain Sheeba and compared it to genomes from H. pylori. The conserved core genes between the genomes are so similar that the host jump probably occurred within the last 200,000 (range 50,000-400,000 years. However, the Sheeba genome also possesses unique features that indicate the direction of the host jump, namely from early humans to cats. Sheeba possesses an unusually large number of highly fragmented genes, many encoding outer membrane proteins, which may have been destroyed in order to bypass deleterious responses from the feline host immune system. In addition, the few Sheeba-specific genes that were found include a cluster of genes encoding sialylation of the bacterial cell surface carbohydrates, which were imported by horizontal genetic exchange and might also help to evade host immune defenses. These results provide a genomic basis for elucidating molecular events that allow bacteria to adapt to novel animal hosts.

What's Special about Human Imitation? A Comparison with Enculturated Apes.

Science.gov (United States)

Subiaul, Francys

2016-07-07

What, if anything, is special about human imitation? An evaluation of enculturated apes' imitation skills, a "best case scenario" of non-human apes' imitation performance, reveals important similarities and differences between this special population of apes and human children. Candidates for shared imitation mechanisms include the ability to imitate various familiar transitive responses and object-object actions that involve familiar tools. Candidates for uniquely derived imitation mechanisms include: imitating novel transitive actions and novel tool-using responses as well as imitating opaque or intransitive gestures, regardless of familiarity. While the evidence demonstrates that enculturated apes outperform non-enculturated apes and perform more like human children, all apes, regardless of rearing history, generally excel at imitating familiar, over-rehearsed responses and are poor, relative to human children, at imitating novel, opaque or intransitive responses. Given the similarities between the sensory and motor systems of preschool age human children and non-human apes, it is unlikely that differences in sensory input and/or motor-output alone explain the observed discontinuities in imitation performance. The special rearing history of enculturated apes-including imitation-specific training-further diminishes arguments suggesting that differences are experience-dependent. Here, it is argued that such differences are best explained by distinct, specialized mechanisms that have evolved for copying rules and responses in particular content domains. Uniquely derived social and imitation learning mechanisms may represent adaptations for learning novel communicative gestures and complex tool-use. Given our species' dependence on both language and tools, mechanisms that accelerated learning in these domains are likely to have faced intense selective pressures, starting with the earliest of human ancestors.

Ancient and modern DNA reveal dynamics of domestication and cross-continental dispersal of the dromedary

Science.gov (United States)

Almathen, Faisal; Charruau, Pauline; Mohandesan, Elmira; Mwacharo, Joram M.; Orozco-terWengel, Pablo; Pitt, Daniel; Abdussamad, Abdussamad M.; Uerpmann, Margarethe; Uerpmann, Hans-Peter; De Cupere, Bea; Magee, Peter; Alnaqeeb, Majed A.; Salim, Bashir; Raziq, Abdul; Dessie, Tadelle; Abdelhadi, Omer M.; Banabazi, Mohammad H.; Al-Eknah, Marzook; Walzer, Chris; Faye, Bernard; Hofreiter, Michael; Peters, Joris; Hanotte, Olivier

2016-01-01

Dromedaries have been fundamental to the development of human societies in arid landscapes and for long-distance trade across hostile hot terrains for 3,000 y. Today they continue to be an important livestock resource in marginal agro-ecological zones. However, the history of dromedary domestication and the influence of ancient trading networks on their genetic structure have remained elusive. We combined ancient DNA sequences of wild and early-domesticated dromedary samples from arid regions with nuclear microsatellite and mitochondrial genotype information from 1,083 extant animals collected across the species’ range. We observe little phylogeographic signal in the modern population, indicative of extensive gene flow and virtually affecting all regions except East Africa, where dromedary populations have remained relatively isolated. In agreement with archaeological findings, we identify wild dromedaries from the southeast Arabian Peninsula among the founders of the domestic dromedary gene pool. Approximate Bayesian computations further support the “restocking from the wild” hypothesis, with an initial domestication followed by introgression from individuals from wild, now-extinct populations. Compared with other livestock, which show a long history of gene flow with their wild ancestors, we find a high initial diversity relative to the native distribution of the wild ancestor on the Arabian Peninsula and to the brief coexistence of early-domesticated and wild individuals. This study also demonstrates the potential to retrieve ancient DNA sequences from osseous remains excavated in hot and dry desert environments. PMID:27162355

The influence of social environment in early life on the behavior, stress response, and reproductive system of adult male Norway rats selected for different attitudes to humans.

Science.gov (United States)

Gulevich, R G; Shikhevich, S G; Konoshenko, M Yu; Kozhemyakina, R V; Herbeck, Yu E; Prasolova, L A; Oskina, I N; Plyusnina, I Z

2015-05-15

The influence of social disturbance in early life on behavior, response of blood corticosterone level to restraint stress, and endocrine and morphometric indices of the testes was studied in 2-month Norway rat males from three populations: not selected for behavior (unselected), selected for against aggression to humans (tame), and selected for increased aggression to humans (aggressive). The experimental social disturbance included early weaning, daily replacement of cagemates from days 19 to 25, and subsequent housing in twos till the age of 2months. The social disturbance increased the latent period of aggressive behavior in the social interaction test in unselected males and reduced relative testis weights in comparison to the corresponding control groups. In addition, experimental unselected rats had smaller diameters of seminiferous tubules and lower blood testosterone levels. In the experimental group, tame rats had lower basal corticosterone levels, and aggressive animals had lower hormone levels after restraint stress in comparison to the control. The results suggest that the selection in two directions for attitude to humans modifies the response of male rats to social disturbance in early life. In this regard, the selected rat populations may be viewed as a model for investigation of (1) neuroendocrinal mechanisms responsible for the manifestation of aggression and (2) interaction of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal systems in stress. Copyright © 2015 Elsevier Inc. All rights reserved.

Human Disturbance during Early Life Impairs Nestling Growth in Birds Inhabiting a Nature Recreation Area.

Science.gov (United States)

Remacha, Carolina; Delgado, Juan Antonio; Bulaic, Mateja; Pérez-Tris, Javier

2016-01-01

Nature recreation conflicts with conservation, but its impacts on wildlife are not fully understood. Where recreation is not regulated, visitors to natural areas may gather in large numbers on weekends and holidays. This may increase variance in fitness in wild populations, if individuals whose critical life cycle stages coincide with periods of high human disturbance are at a disadvantage. We studied nestling development of blue tits (Cyanistes caeruleus) in a natural area where recreation activities intensify during weekends and other public holidays at picnic and leisure facilities, but not in the surrounding woods. In nests located near recreation facilities, blue tit nestlings that hatched during holidays developed slowly, and fledged with low body mass and poor body condition. However, nestlings that hatched outside of holidays and weekends in these nest boxes developed normally, eventually attaining similar phenotypes as those hatching in the surrounding woods. Within-brood variance in body mass was also higher in broods that began growing during holidays in disturbed areas. Our results show that early disturbance events may have negative consequences for wild birds if they overlap with critical stages of development, unveiling otherwise cryptic impacts of human activities. These new findings may help managers better regulate nature recreation.

Human Disturbance during Early Life Impairs Nestling Growth in Birds Inhabiting a Nature Recreation Area.

Directory of Open Access Journals (Sweden)

Carolina Remacha

Full Text Available Nature recreation conflicts with conservation, but its impacts on wildlife are not fully understood. Where recreation is not regulated, visitors to natural areas may gather in large numbers on weekends and holidays. This may increase variance in fitness in wild populations, if individuals whose critical life cycle stages coincide with periods of high human disturbance are at a disadvantage. We studied nestling development of blue tits (Cyanistes caeruleus in a natural area where recreation activities intensify during weekends and other public holidays at picnic and leisure facilities, but not in the surrounding woods. In nests located near recreation facilities, blue tit nestlings that hatched during holidays developed slowly, and fledged with low body mass and poor body condition. However, nestlings that hatched outside of holidays and weekends in these nest boxes developed normally, eventually attaining similar phenotypes as those hatching in the surrounding woods. Within-brood variance in body mass was also higher in broods that began growing during holidays in disturbed areas. Our results show that early disturbance events may have negative consequences for wild birds if they overlap with critical stages of development, unveiling otherwise cryptic impacts of human activities. These new findings may help managers better regulate nature recreation.

Early life adversity: Lasting consequences for emotional learning

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Harm J. Krugers

2017-02-01

Full Text Available The early postnatal period is a highly sensitive time period for the developing brain, both in humans and rodents. During this time window, exposure to adverse experiences can lastingly impact cognitive and emotional development. In this review, we briefly discuss human and rodent studies investigating how exposure to adverse early life conditions – mainly related to quality of parental care - affects brain activity, brain structure, cognition and emotional responses later in life. We discuss the evidence that early life adversity hampers later hippocampal and prefrontal cortex functions, while increasing amygdala activity, and the sensitivity to stressors and emotional behavior later in life. Exposure to early life stress may thus on the one hand promote behavioral adaptation to potentially threatening conditions later in life –at the cost of contextual memory formation in less threatening situations- but may on the other hand also increase the sensitivity to develop stress-related and anxiety disorders in vulnerable individuals.

Anchoring the landscape: human utilization of the Cerro Gavilán 2 rockshelter, Middle Orinoco, from the Early Holocene to the present

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Kay Scaramelli

Full Text Available Abstract Initial archaeological investigations at Cerro Gavilán 2, a rockshelter located in the Bolívar State of Venezuela, reveal evidence for human activity that spans the Early Holocene to the present. This report summarizes the information obtained through surface collection, limited excavation, and documentation of the surface features and rock art in the cave. Accelerator mass spectrometry (AMS 14C analysis established dates from excavated strata that range between 9250 ± 60 BP to 3440 ± 40 BP, and are associated with a unifacial flake technology and charred faunal and floral remains, whereas surface remains span the known ceramic sequence for the area. Rock art corresponds to distinctive superimposed styles that indicate continual repainting of the cave through time, serving to anchor the site to the landscape for multiple societies inhabiting the region. It is suggested that the shelter may have fulfilled different functions over time and a sequence of seasonal residential, ritual, and funerary activities is proposed. The rich cultural context found in Cerro Gavilán 2 contributes to advances in Amazonian archaeology that are redefining our knowledge of early developments and the complexity of human/environmental interactions in tropical America.

Evolution of the NANOG pseudogene family in the human and chimpanzee genomes

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Maughan Peter J

2006-02-01

Full Text Available Abstract Background The NANOG gene is expressed in mammalian embryonic stem cells where it maintains cellular pluripotency. An unusually large family of pseudogenes arose from it with one unprocessed and ten processed pseudogenes in the human genome. This article compares the NANOG gene and its pseudogenes in the human and chimpanzee genomes and derives an evolutionary history of this pseudogene family. Results The NANOG gene and all pseudogenes except NANOGP8 are present at their expected orthologous chromosomal positions in the chimpanzee genome when compared to the human genome, indicating that their origins predate the human-chimpanzee divergence. Analysis of flanking DNA sequences demonstrates that NANOGP8 is absent from the chimpanzee genome. Conclusion Based on the most parsimonious ordering of inferred source-gene mutations, the deduced evolutionary origins for the NANOG pseudogene family in the human and chimpanzee genomes, in order of most ancient to most recent, are NANOGP6, NANOGP5, NANOGP3, NANOGP10, NANOGP2, NANOGP9, NANOGP7, NANOGP1, and NANOGP4. All of these pseudogenes were fixed in the genome of the human-chimpanzee common ancestor. NANOGP8 is the most recent pseudogene and it originated exclusively in the human lineage after the human-chimpanzee divergence. NANOGP1 is apparently an unprocessed pseudogene. Comparison of its sequence to the functional NANOG gene's reading frame suggests that this apparent pseudogene remained functional after duplication and, therefore, was subject to selection-driven conservation of its reading frame, and that it may retain some functionality or that its loss of function may be evolutionarily recent.

40 CFR 26.1123 - Early termination of research.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Early termination of research. 26.1123 Section 26.1123 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN... Exposure of Non-pregnant, Non-nursing Adults § 26.1123 Early termination of research. The Administrator may...

association between early life malnutrition and the size of lumbar ...

African Journals Online (AJOL)

Objective: To determine the relationship between early life malnutrition and the development of lumbar ... incriminate such predictors as poverty, aridity and human development which can be reduced ..... relationship with early childhood caries.

Cultural assemblages show nested structure in humans and chimpanzees but not orangutans.

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Kamilar, Jason M; Atkinson, Quentin D

2014-01-07

The evolution of hominin culture is well-documented in the archeological and fossil record, but such a record is largely absent for nonhuman primates. An alternative approach to studying cultural evolution is to examine patterns of modern cultural variation. In this article we measure nestedness across human and great ape "cultural repertoires" to gain insight into the accumulation and maintenance of putative cultural diversity in these species. Cultural assemblages are nested if cultures with a small repertoire of traits tend to comprise a proper subset of those traits present in more complex cultures. This nesting will occur if some traits are sequentially gained or lost, which may be because of the differential dispersal or extinction of traits. Here we apply statistical tools from ecology to examine the degree of nestedness in four datasets documenting the presence or absence of specific cultural traits across indigenous human populations in North America and New Guinea. We then compare the human data to patterns observed for putative cultural traits in chimpanzee and orangutan populations. In both humans and chimpanzees, cultural diversity is highly nonrandom, showing significant nested structure for all of the datasets examined. We find no evidence for nestedness in the orangutan cultural data. These findings are consistent with a sequential "layering" of cultural diversity in humans and chimpanzees, but not orangutans. Such an interpretation implies that the traits required for sequential cultural evolution first appeared in the last common ancestor of chimpanzees and humans.

Mitochondrial DNA diversity of present-day Aboriginal Australians and implications for human evolution in Oceania.

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Nagle, Nano; Ballantyne, Kaye N; van Oven, Mannis; Tyler-Smith, Chris; Xue, Yali; Wilcox, Stephen; Wilcox, Leah; Turkalov, Rust; van Oorschot, Roland A H; van Holst Pellekaan, Sheila; Schurr, Theodore G; McAllister, Peter; Williams, Lesley; Kayser, Manfred; Mitchell, R John

2017-03-01

Aboriginal Australians are one of the more poorly studied populations from the standpoint of human evolution and genetic diversity. Thus, to investigate their genetic diversity, the possible date of their ancestors' arrival and their relationships with neighboring populations, we analyzed mitochondrial DNA (mtDNA) diversity in a large sample of Aboriginal Australians. Selected mtDNA single-nucleotide polymorphisms and the hypervariable segment haplotypes were analyzed in 594 Aboriginal Australians drawn from locations across the continent, chiefly from regions not previously sampled. Most (~78%) samples could be assigned to mtDNA haplogroups indigenous to Australia. The indigenous haplogroups were all ancient (with estimated ages >40 000 years) and geographically widespread across the continent. The most common haplogroup was P (44%) followed by S (23%) and M42a (9%). There was some geographic structure at the haplotype level. The estimated ages of the indigenous haplogroups range from 39 000 to 55 000 years, dates that fit well with the estimated date of colonization of Australia based on archeological evidence (~47 000 years ago). The distribution of mtDNA haplogroups in Australia and New Guinea supports the hypothesis that the ancestors of Aboriginal Australians entered Sahul through at least two entry points. The mtDNA data give no support to the hypothesis of secondary gene flow into Australia during the Holocene, but instead suggest long-term isolation of the continent.

Health and Ancestors: The Case of South Africa and Beyond

African Journals Online (AJOL)

denise

The IPJP is a joint project of the Humanities Faculty of the University of Johannesburg (South Africa) and Edith Cowan ... This work is licensed to the publisher under the Creative Commons Attributions License 3.0 .... that can be successful without the guidance and co- .... the failure by the family to perform a certain ritual.

An organizational early-warning system for safety, health, and environmental crises

International Nuclear Information System (INIS)

Shrivastava, P.

1992-01-01

Early-warning systems have played an important role in preventing major industrial accidents and technological disasters. These systems record critical operating and performance parameters and raise warnings or alarms if these parameters cross acceptable limits. Most early-warning systems used in hazardous industries focus on the technological system and to a lesser extent on their human operators. However, industrial disasters are caused not only by technological and human failure, but also by organizational, regulatory, infrastructural, and community preparedness failures. Hazardous industries can benefit from the development of early-warning systems that have a broader scope than the core technology. These systems could cover financial, human resource, organizational policies, regulatory, infrastructural, and community-related variables. This paper develops some basic concepts that can help build managerially useful early-warning systems for safety, health, and environmental (SHE) incidents. It identifies variables that should be tracked, the threshold levels for these variables, and possible managerial reactions to warnings

Hunter-gatherer energetics and human obesity.

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Pontzer, Herman; Raichlen, David A; Wood, Brian M; Mabulla, Audax Z P; Racette, Susan B; Marlowe, Frank W

2012-01-01

Western lifestyles differ markedly from those of our hunter-gatherer ancestors, and these differences in diet and activity level are often implicated in the global obesity pandemic. However, few physiological data for hunter-gatherer populations are available to test these models of obesity. In this study, we used the doubly-labeled water method to measure total daily energy expenditure (kCal/day) in Hadza hunter-gatherers to test whether foragers expend more energy each day than their Western counterparts. As expected, physical activity level, PAL, was greater among Hadza foragers than among Westerners. Nonetheless, average daily energy expenditure of traditional Hadza foragers was no different than that of Westerners after controlling for body size. The metabolic cost of walking (kcal kg(-1) m(-1)) and resting (kcal kg(-1) s(-1)) were also similar among Hadza and Western groups. The similarity in metabolic rates across a broad range of cultures challenges current models of obesity suggesting that Western lifestyles lead to decreased energy expenditure. We hypothesize that human daily energy expenditure may be an evolved physiological trait largely independent of cultural differences.

Distractor Effect of Auditory Rhythms on Self-Paced Tapping in Chimpanzees and Humans

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Hattori, Yuko; Tomonaga, Masaki; Matsuzawa, Tetsuro

2015-01-01

Humans tend to spontaneously align their movements in response to visual (e.g., swinging pendulum) and auditory rhythms (e.g., hearing music while walking). Particularly in the case of the response to auditory rhythms, neuroscientific research has indicated that motor resources are also recruited while perceiving an auditory rhythm (or regular pulse), suggesting a tight link between the auditory and motor systems in the human brain. However, the evolutionary origin of spontaneous responses to auditory rhythms is unclear. Here, we report that chimpanzees and humans show a similar distractor effect in perceiving isochronous rhythms during rhythmic movement. We used isochronous auditory rhythms as distractor stimuli during self-paced alternate tapping of two keys of an electronic keyboard by humans and chimpanzees. When the tempo was similar to their spontaneous motor tempo, tapping onset was influenced by intermittent entrainment to auditory rhythms. Although this effect itself is not an advanced rhythmic ability such as dancing or singing, our results suggest that, to some extent, the biological foundation for spontaneous responses to auditory rhythms was already deeply rooted in the common ancestor of chimpanzees and humans, 6 million years ago. This also suggests the possibility of a common attentional mechanism, as proposed by the dynamic attending theory, underlying the effect of perceiving external rhythms on motor movement. PMID:26132703

Distractor Effect of Auditory Rhythms on Self-Paced Tapping in Chimpanzees and Humans.

Directory of Open Access Journals (Sweden)

Yuko Hattori

Full Text Available Humans tend to spontaneously align their movements in response to visual (e.g., swinging pendulum and auditory rhythms (e.g., hearing music while walking. Particularly in the case of the response to auditory rhythms, neuroscientific research has indicated that motor resources are also recruited while perceiving an auditory rhythm (or regular pulse, suggesting a tight link between the auditory and motor systems in the human brain. However, the evolutionary origin of spontaneous responses to auditory rhythms is unclear. Here, we report that chimpanzees and humans show a similar distractor effect in perceiving isochronous rhythms during rhythmic movement. We used isochronous auditory rhythms as distractor stimuli during self-paced alternate tapping of two keys of an electronic keyboard by humans and chimpanzees. When the tempo was similar to their spontaneous motor tempo, tapping onset was influenced by intermittent entrainment to auditory rhythms. Although this effect itself is not an advanced rhythmic ability such as dancing or singing, our results suggest that, to some extent, the biological foundation for spontaneous responses to auditory rhythms was already deeply rooted in the common ancestor of chimpanzees and humans, 6 million years ago. This also suggests the possibility of a common attentional mechanism, as proposed by the dynamic attending theory, underlying the effect of perceiving external rhythms on motor movement.

Degradation of p53 by human Alphapapillomavirus E6 proteins shows a stronger correlation with phylogeny than oncogenicity.

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Leiping Fu

2010-09-01

Full Text Available Human Papillomavirus (HPV E6 induced p53 degradation is thought to be an essential activity by which high-risk human Alphapapillomaviruses (alpha-HPVs contribute to cervical cancer development. However, most of our understanding is derived from the comparison of HPV16 and HPV11. These two viruses are relatively distinct viruses, making the extrapolation of these results difficult. In the present study, we expand the tested strains (types to include members of all known HPV species groups within the Alphapapillomavirus genus.We report the biochemical activity of E6 proteins from 27 HPV types representing all alpha-HPV species groups to degrade p53 in human cells. Expression of E6 from all HPV types epidemiologically classified as group 1 carcinogens significantly reduced p53 levels. However, several types not associated with cancer (e.g., HPV53, HPV70 and HPV71 were equally active in degrading p53. HPV types within species groups alpha 5, 6, 7, 9 and 11 share a most recent common ancestor (MRCA and all contain E6 ORFs that degrade p53. A unique exception, HPV71 E6 ORF that degraded p53 was outside this clade and is one of the most prevalent HPV types infecting the cervix in a population-based study of 10,000 women. Alignment of E6 ORFs identified an amino acid site that was highly correlated with the biochemical ability to degrade p53. Alteration of this amino acid in HPV71 E6 abrogated its ability to degrade p53, while alteration of this site in HPV71-related HPV90 and HPV106 E6s enhanced their capacity to degrade p53.These data suggest that the alpha-HPV E6 proteins' ability to degrade p53 is an evolved phenotype inherited from a most recent common ancestor of the high-risk species that does not always segregate with carcinogenicity. In addition, we identified an amino-acid residue strongly correlated with viral p53 degrading potential.

Evaluation of an in vitro faecal degradation method for early assessment of the impact of colonic degradation on colonic absorption in humans.

Science.gov (United States)

Tannergren, Christer; Borde, Anders; Boreström, Cecilia; Abrahamsson, Bertil; Lindahl, Anders

2014-06-16

The objective of this study was to develop and evaluate an in vitro method to investigate bacterial-mediated luminal degradation of drugs in colon in humans. This would be a valuable tool for the assessment of drug candidates during early drug development, especially for compounds intended to be developed as oral extended release formulations. Freshly prepared faecal homogenate from healthy human volunteers (n=3-18), dog (n=6) and rat (colon and caecal content, n=3) was homogenised with 3.8 parts (w/w) physiological saline under anaerobical conditions. Four model compounds (almokalant, budesonide, ximelagatran and metoprolol) were then incubated (n=3-18) separately in the human faecal homogenate for up to 120min at 37°C. In addition, ximelagatran was also incubated in the faecal or colonic content from dog and rat. The mean (±SD) in vitro half-life for almokalant, budesonide and ximelagatran was 39±1, 68±21 and 26±12min, respectively, in the human faecal homogenate. Metoprolol was found to be stable in the in vitro model. The in vitro degradation data was then compared to literature data on fraction absorbed after direct colon administration in humans. The percentage of drug remaining after 60min of in vitro incubation correlated (R(2)=0.90) with the fraction absorbed from colon in humans. The mean in vitro half-life of ximelagatran was similar in human faeces (26±12min) and rat colon content (34±31min), but significantly (pdegradation in vivo was rapidly degraded in the faecal homogenates as well as quantitatively since a correlation was established between percentage degraded in vitro at 60min and fraction absorbed in the colon for the model drugs, which have no other absorption limiting properties. Also, the method is easy to use from a technical point of view, which suggests that the method is suitable for use in early assessment of colonic absorption of extended release formulation candidates. Further improvement of the confidence in the use of the

Prior acetaminophen consumption impacts the early adaptive cellular response of human skeletal muscle to resistance exercise.

Science.gov (United States)

D'Lugos, Andrew C; Patel, Shivam H; Ormsby, Jordan C; Curtis, Donald P; Fry, Christopher S; Carroll, Chad C; Dickinson, Jared M

2018-04-01

Resistance exercise (RE) is a powerful stimulus for skeletal muscle adaptation. Previous data demonstrate that cyclooxygenase (COX)-inhibiting drugs alter the cellular mechanisms regulating the adaptive response of skeletal muscle. The purpose of this study was to determine whether prior consumption of the COX inhibitor acetaminophen (APAP) alters the immediate adaptive cellular response in human skeletal muscle after RE. In a double-blinded, randomized, crossover design, healthy young men ( n = 8, 25 ± 1 yr) performed two trials of unilateral knee extension RE (8 sets, 10 reps, 65% max strength). Subjects ingested either APAP (1,000 mg/6 h) or placebo (PLA) for 24 h before RE (final dose consumed immediately after RE). Muscle biopsies (vastus lateralis) were collected at rest and 1 h and 3 h after exercise. Mammalian target of rapamycin (mTOR) complex 1 signaling was assessed through immunoblot and immunohistochemistry, and mRNA expression of myogenic genes was examined via RT-qPCR. At 1 h p-rpS6 Ser240/244 was increased in both groups but to a greater extent in PLA. At 3 h p-S6K1 Thr389 was elevated only in PLA. Furthermore, localization of mTOR to the lysosome (LAMP2) in myosin heavy chain (MHC) II fibers increased 3 h after exercise only in PLA. mTOR-LAMP2 colocalization in MHC I fibers was greater in PLA vs. APAP 1 h after exercise. Myostatin mRNA expression was reduced 1 h after exercise only in PLA. MYF6 mRNA expression was increased 1 h and 3 h after exercise only in APAP. APAP consumption appears to alter the early adaptive cellular response of skeletal muscle to RE. These findings further highlight the mechanisms through which COX-inhibiting drugs impact the adaptive response of skeletal muscle to exercise. NEW & NOTEWORTHY The extent to which the cellular reaction to acetaminophen impacts the mechanisms regulating the adaptive response of human skeletal muscle to resistance exercise is not well understood. Consumption of acetaminophen before

The human dimension of fire regimes on Earth.

Science.gov (United States)

Bowman, David M J S; Balch, Jennifer; Artaxo, Paulo; Bond, William J; Cochrane, Mark A; D'Antonio, Carla M; Defries, Ruth; Johnston, Fay H; Keeley, Jon E; Krawchuk, Meg A; Kull, Christian A; Mack, Michelle; Moritz, Max A; Pyne, Stephen; Roos, Christopher I; Scott, Andrew C; Sodhi, Navjot S; Swetnam, Thomas W; Whittaker, Robert

2011-12-01

Humans and their ancestors are unique in being a fire-making species, but 'natural' (i.e. independent of humans) fires have an ancient, geological history on Earth. Natural fires have influenced biological evolution and global biogeochemical cycles, making fire integral to the functioning of some biomes. Globally, debate rages about the impact on ecosystems of prehistoric human-set fires, with views ranging from catastrophic to negligible. Understanding of the diversity of human fire regimes on Earth in the past, present and future remains rudimentary. It remains uncertain how humans have caused a departure from 'natural' background levels that vary with climate change. Available evidence shows that modern humans can increase or decrease background levels of natural fire activity by clearing forests, promoting grazing, dispersing plants, altering ignition patterns and actively suppressing fires, thereby causing substantial ecosystem changes and loss of biodiversity. Some of these contemporary fire regimes cause substantial economic disruptions owing to the destruction of infrastructure, degradation of ecosystem services, loss of life, and smoke-related health effects. These episodic disasters help frame negative public attitudes towards landscape fires, despite the need for burning to sustain some ecosystems. Greenhouse gas-induced warming and changes in the hydrological cycle may increase the occurrence of large, severe fires, with potentially significant feedbacks to the Earth system. Improved understanding of human fire regimes demands: (1) better data on past and current human influences on fire regimes to enable global comparative analyses, (2) a greater understanding of different cultural traditions of landscape burning and their positive and negative social, economic and ecological effects, and (3) more realistic representations of anthropogenic fire in global vegetation and climate change models. We provide an historical framework to promote understanding

The human dimension of fire regimes on Earth

Science.gov (United States)

Bowman, David M.J.S.; Balch, Jennifer; Artaxo, Paulo; Bond, William J.; Cochrane, Mark A.; D'Antonio, Carla M.; DeFries, Ruth; Johnston, Fay H.; Keeley, Jon E.; Krawchuk, Meg A.; Kull, Christian A.; Michelle, Mack; Moritz, Max A.; Pyne, Stephen; Roos, Christopher I.; Scott, Andrew C.; Sodhi, Navjot S.; Swetnam, Thomas W.

2011-01-01

Humans and their ancestors are unique in being a fire-making species, but 'natural' (i.e. independent of humans) fires have an ancient, geological history on Earth. Natural fires have influenced biological evolution and global biogeochemical cycles, making fire integral to the functioning of some biomes. Globally, debate rages about the impact on ecosystems of prehistoric human-set fires, with views ranging from catastrophic to negligible. Understanding of the diversity of human fire regimes on Earth in the past, present and future remains rudimentary. It remains uncertain how humans have caused a departure from 'natural' background levels that vary with climate change. Available evidence shows that modern humans can increase or decrease background levels of natural fire activity by clearing forests, promoting grazing, dispersing plants, altering ignition patterns and actively suppressing fires, thereby causing substantial ecosystem changes and loss of biodiversity. Some of these contemporary fire regimes cause substantial economic disruptions owing to the destruction of infrastructure, degradation of ecosystem services, loss of life, and smoke-related health effects. These episodic disasters help frame negative public attitudes towards landscape fires, despite the need for burning to sustain some ecosystems. Greenhouse gas-induced warming and changes in the hydrological cycle may increase the occurrence of large, severe fires, with potentially significant feedbacks to the Earth system. Improved understanding of human fire regimes demands: (1) better data on past and current human influences on fire regimes to enable global comparative analyses, (2) a greater understanding of different cultural traditions of landscape burning and their positive and negative social, economic and ecological effects, and (3) more realistic representations of anthropogenic fire in global vegetation and climate change models. We provide an historical framework to promote understanding

A Systematic Literature Review and Meta-Regression Analysis on Early-Life Energy Restriction and Cancer Risk in Humans.

Science.gov (United States)

Elands, Rachel J J; Simons, Colinda C J M; Dongen, Martien van; Schouten, Leo J; Verhage, Bas A J; van den Brandt, Piet A; Weijenberg, Matty P

2016-01-01

In animal models, long-term moderate energy restriction (ER) is reported to decelerate carcinogenesis, whereas the effect of severe ER is inconsistent. The impact of early-life ER on cancer risk has never been reviewed systematically and quantitatively based on observational studies in humans. We conducted a systematic review of observational studies and a meta-(regression) analysis on cohort studies to clarify the association between early-life ER and organ site-specific cancer risk. PubMed and EMBASE (1982 -August 2015) were searched for observational studies. Summary relative risks (RRs) were estimated using a random effects model when available ≥3 studies. Twenty-four studies were included. Eleven publications, emanating from seven prospective cohort studies and some reporting on multiple cancer endpoints, met the inclusion criteria for quantitative analysis. Women exposed to early-life ER (ranging from 220-1660 kcal/day) had a higher breast cancer risk than those not exposed (RRRE all ages = 1.28, 95% CI: 1.05-1.56; RRRE for 10-20 years of age = 1.21, 95% CI: 1.09-1.34). Men exposed to early-life ER (ranging from 220-800kcal/day) had a higher prostate cancer risk than those not exposed (RRRE = 1.16, 95% CI: 1.03-1.30). Summary relative risks were not computed for colorectal cancer, because of heterogeneity, and for stomach-, pancreas-, ovarian-, and respiratory cancer because there were <3 available studies. Longer duration of exposure to ER, after adjustment for severity, was positively associated with overall cancer risk in women (p = 0.02). Ecological studies suggest that less severe ER is generally associated with a reduced risk of cancer. Early-life transient severe ER seems to be associated with increased cancer risk in the breast (particularly ER exposure at adolescent age) and prostate. The duration, rather than severity of exposure to ER, seems to positively influence relative risk estimates. This result should be interpreted with caution due to the

Ecophysiological characterization of early successional biological soil crusts in heavily human-impacted areas

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Szyja, Michelle; Büdel, Burkhard; Colesie, Claudia

2018-04-01

Ecophysiological characterizations of photoautotrophic communities are not only necessary to identify the response of carbon fixation related to different climatic factors, but also to evaluate risks connected to changing environments. In biological soil crusts (BSCs), the description of ecophysiological features is difficult, due to the high variability in taxonomic composition and variable methodologies applied. Especially for BSCs in early successional stages, the available datasets are rare or focused on individual constituents, although these crusts may represent the only photoautotrophic component in many heavily disturbed ruderal areas, such as parking lots or building areas with increasing surface area worldwide. We analyzed the response of photosynthesis and respiration to changing BSC water contents (WCs), temperature and light in two early successional BSCs. We investigated whether the response of these parameters was different between intact BSC and the isolated dominating components. BSCs dominated by the cyanobacterium Nostoc commune and dominated by the green alga Zygogonium ericetorum were examined. A major divergence between the two BSCs was their absolute carbon fixation rate on a chlorophyll basis, which was significantly higher for the cyanobacterial crust. Nevertheless, independent of species composition, both crust types and their isolated organisms had convergent features such as high light acclimatization and a minor and very late-occurring depression in carbon uptake at water suprasaturation. This particular setup of ecophysiological features may enable these communities to cope with a high variety of climatic stresses and may therefore be a reason for their success in heavily disturbed areas with ongoing human impact. However, the shape of the response was different for intact BSC compared to separated organisms, especially in absolute net photosynthesis (NP) rates. This emphasizes the importance of measuring intact BSCs under natural

Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche

Science.gov (United States)

Van Doorslaer, Koenraad; DeSalle, Rob; Einstein, Mark H.; Burk, Robert D.

2015-01-01

In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential) is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution. PMID:26086730

Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche.

Directory of Open Access Journals (Sweden)

Koenraad Van Doorslaer

2015-06-01

Full Text Available In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution.

Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche.

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Van Doorslaer, Koenraad; DeSalle, Rob; Einstein, Mark H; Burk, Robert D

2015-06-01

In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential) is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution.

What’s Special about Human Imitation? A Comparison with Enculturated Apes

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Subiaul, Francys

2016-01-01

What, if anything, is special about human imitation? An evaluation of enculturated apes’ imitation skills, a “best case scenario” of non-human apes’ imitation performance, reveals important similarities and differences between this special population of apes and human children. Candidates for shared imitation mechanisms include the ability to imitate various familiar transitive responses and object–object actions that involve familiar tools. Candidates for uniquely derived imitation mechanisms include: imitating novel transitive actions and novel tool-using responses as well as imitating opaque or intransitive gestures, regardless of familiarity. While the evidence demonstrates that enculturated apes outperform non-enculturated apes and perform more like human children, all apes, regardless of rearing history, generally excel at imitating familiar, over-rehearsed responses and are poor, relative to human children, at imitating novel, opaque or intransitive responses. Given the similarities between the sensory and motor systems of preschool age human children and non-human apes, it is unlikely that differences in sensory input and/or motor-output alone explain the observed discontinuities in imitation performance. The special rearing history of enculturated apes—including imitation-specific training—further diminishes arguments suggesting that differences are experience-dependent. Here, it is argued that such differences are best explained by distinct, specialized mechanisms that have evolved for copying rules and responses in particular content domains. Uniquely derived social and imitation learning mechanisms may represent adaptations for learning novel communicative gestures and complex tool-use. Given our species’ dependence on both language and tools, mechanisms that accelerated learning in these domains are likely to have faced intense selective pressures, starting with the earliest of human ancestors. PMID:27399786

What’s Special about Human Imitation? A Comparison with Enculturated Apes

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Francys Subiaul

2016-07-01

Full Text Available What, if anything, is special about human imitation? An evaluation of enculturated apes’ imitation skills, a “best case scenario” of non-human apes’ imitation performance, reveals important similarities and differences between this special population of apes and human children. Candidates for shared imitation mechanisms include the ability to imitate various familiar transitive responses and object–object actions that involve familiar tools. Candidates for uniquely derived imitation mechanisms include: imitating novel transitive actions and novel tool-using responses as well as imitating opaque or intransitive gestures, regardless of familiarity. While the evidence demonstrates that enculturated apes outperform non-enculturated apes and perform more like human children, all apes, regardless of rearing history, generally excel at imitating familiar, over-rehearsed responses and are poor, relative to human children, at imitating novel, opaque or intransitive responses. Given the similarities between the sensory and motor systems of preschool age human children and non-human apes, it is unlikely that differences in sensory input and/or motor-output alone explain the observed discontinuities in imitation performance. The special rearing history of enculturated apes—including imitation-specific training—further diminishes arguments suggesting that differences are experience-dependent. Here, it is argued that such differences are best explained by distinct, specialized mechanisms that have evolved for copying rules and responses in particular content domains. Uniquely derived social and imitation learning mechanisms may represent adaptations for learning novel communicative gestures and complex tool-use. Given our species’ dependence on both language and tools, mechanisms that accelerated learning in these domains are likely to have faced intense selective pressures, starting with the earliest of human ancestors.

Synsepalum dulcificum extracts exhibit cytotoxic activity on human colorectal cancer cells and upregulate c-fos and c-jun early apoptotic gene expression

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Jichang Seong

2018-01-01

Full Text Available Objective: To explore cytotoxicity of Synsepalum dulcificum (S. dulcificum Daniell (Sapotaceae on human colon cancer (HCT-116 and HT-29, human monocytic leukemia (THP-1 and normal (HDFn cell lines, and its effect on the expression of early apoptotic genes, c-fos and c-jun. Methods: Leaf, stem and berry of S. dulcificum were separately extracted by using 2 solvents, 10% ethanol (EtOH and 80% methanol (MeOH. PrestoBlue® cell viability assay and qRT-PCR assay were conducted to examine the above objectives respectively. Results: Stem MeOH, stem EtOH, and berry EtOH extracts of S. dulcificum were cytotoxic to HCT-116 and HT-29 human colon cancer cells. For HCT-116, IC50 values of these 3 extracts were not significantly different (P>0.05 from that of the positive control bleomycin (IC50 of 33.57 μg/mL, while for HT-29, IC50 values of these 3 extracts were significantly lower (P<0.05 than that of bleomycin (IC50 of 25.24 μg/mL. None of the extracts were cytotoxic to the THP-1 monocytic leukemia cells and HDFn normal human dermal fibroblasts. For both HCT-116 and HT-29, these extracts significantly up-regulated (P<0.05 the expression of c-fos and c-jun compared to the untreated negative control. Conclusions: The results of this study suggest that cytotoxicity of stem MeOH, stem EtOH, and berry EtOH extracts of S. dulcificum on HCT-116 and HT-29 colon cancer cells is due to the induced apoptosis which is caused by the up-regulation of the expression of early apoptotic genes, c-fos and c-jun.

Nicolae Milescu Spătarul - ancestor of a Nobel Laureate - Ilia I. Mecinikov. Part I. Nicolae Milescu-Spătarul’s secular European impact; 1st of June 2011 - 375 years since the birth of the European erudite

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Dan RIGA

2011-01-01

Full Text Available The culture of tradition and patrimony is an act of civilization, as well as one of identitaryeducation. This is why the promotion of restitution comprises all areas of progress and humancreation.Nicolae Milescu-Spătarul (b. 1636 in Moldavia - d. 1708 in Russia was an eruditehumanist scholar, an encyclopaedist, a theologist, diplomat, historian, geographer, ethnographer,translator, memorialist and a polyglot (Romanian, ancient and modern Greek, Latin, Turkish andSlavonic-Russian. Commemorating and honouring this figure, of European and Eurasianimportance alike, is a debt of honour: 1958 – 250 years since death; 2011 – 375 years since birth.At this time, the need to fully publish his work arises, as a large part of it is still kept in libraries,archives and European private collections in the form of manuscripts. Nicolae Milescu-Spătarulwas the ancestor of the Nobel Laureate (1908, scientist Ilia I. Mecinikov (1845-1916.The work reveals the great scholar’s (eastern, but also western, European and Asiancultural, scientific and diplomatic impact – at that moment and throughout time – but also theSorin Riga, Dan Riga, Vasile Man - Nicolae Milescu Spătarul - ancestor of a Nobel Laureate - Ilia I. Mecinikov impact of his vast work. The remarkable monograph The Description of China (58 chapters was published in Romanian only in 1958.

Inferring human colonization history using a copying model.

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Garrett Hellenthal

2008-05-01

Full Text Available Genome-wide scans of genetic variation can potentially provide detailed information on how modern humans colonized the world but require new methods of analysis. We introduce a statistical approach that uses Single Nucleotide Polymorphism (SNP data to identify sharing of chromosomal segments between populations and uses the pattern of sharing to reconstruct a detailed colonization scenario. We apply our model to the SNP data for the 53 populations of the Human Genome Diversity Project described in Conrad et al. (Nature Genetics 38,1251-60, 2006. Our results are consistent with the consensus view of a single "Out-of-Africa" bottleneck and serial dilution of diversity during global colonization, including a prominent East Asian bottleneck. They also suggest novel details including: (1 the most northerly East Asian population in the sample (Yakut has received a significant genetic contribution from the ancestors of the most northerly European one (Orcadian. (2 Native North [corrected] Americans have received ancestry from a source closely related to modern North-East Asians (Mongolians and Oroquen that is distinct from the sources for native South [corrected] Americans, implying multiple waves of migration into the Americas. A detailed depiction of the peopling of the world is available in animated form.

The Role of Ontogeny in the Evolution of Human Cooperation.

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Tomasello, Michael; Gonzalez-Cabrera, Ivan

2017-09-01

To explain the evolutionary emergence of uniquely human skills and motivations for cooperation, Tomasello et al. (2012, in Current Anthropology 53(6):673-92) proposed the interdependence hypothesis. The key adaptive context in this account was the obligate collaborative foraging of early human adults. Hawkes (2014, in Human Nature 25(1):28-48), following Hrdy (Mothers and Others, Harvard University Press, 2009), provided an alternative account for the emergence of uniquely human cooperative skills in which the key was early human infants' attempts to solicit care and attention from adults in a cooperative breeding context. Here we attempt to reconcile these two accounts. Our composite account accepts Hrdy's and Hawkes's contention that the extremely early emergence of human infants' cooperative skills suggests an important role for cooperative breeding as adaptive context, perhaps in early Homo. But our account also insists that human cooperation goes well beyond these nascent skills to include such things as the communicative and cultural conventions, norms, and institutions created by later Homo and early modern humans to deal with adult problems of social coordination. As part of this account we hypothesize how each of the main stages of human ontogeny (infancy, childhood, adolescence) was transformed during evolution both by infants' cooperative skills "migrating up" in age and by adults' cooperative skills "migrating down" in age.

Whole genome sequencing of Mycobacterium bovis to obtain molecular fingerprints in human and cattle isolates from Baja California, Mexico.

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Sandoval-Azuara, Sarai Estrella; Muñiz-Salazar, Raquel; Perea-Jacobo, Ricardo; Robbe-Austerman, Suelee; Perera-Ortiz, Alejandro; López-Valencia, Gilberto; Bravo, Doris M; Sanchez-Flores, Alejandro; Miranda-Guzmán, Daniela; Flores-López, Carlos Alberto; Zenteno-Cuevas, Roberto; Laniado-Laborín, Rafael; de la Cruz, Fabiola Lafarga; Stuber, Tod P

2017-10-01

To determine genetic diversity by comparing the whole genome sequences of cattle and human Mycobacterium bovis isolates from Baja California. A whole genome sequencing strategy was used to obtain the molecular fingerprints of 172 isolates of M. bovis obtained from Baja California, Mexico; 155 isolates were from cattle and 17 isolates were from humans. Spoligotypes were characterized in silico and single nucleotide polymorphism (SNP) differences between the isolates were evaluated. A total of 12 M. bovis spoligotype patterns were identified in cattle and humans. Two predominant spoligotypes patterns were seen in both cattle and humans: SB0145 and SB1040. The SB0145 spoligotype represented 59% of cattle isolates (n=91) and 65% of human isolates (n=11), while the SB1040 spoligotype represented 30% of cattle isolates (n=47) and 30% of human isolates (n=5). When evaluating SNP differences, the human isolates were intimately intertwined with the cattle isolates. All isolates from humans had spoligotype patterns that matched those observed in the cattle isolates, and all human isolates shared common ancestors with cattle in Baja California based on SNP analysis. This suggests that most human tuberculosis caused by M. bovis in Baja California is derived from M. bovis circulating in Baja California cattle. These results reinforce the importance of bovine tuberculosis surveillance and control in this region. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

B Subunit of Human Chorionic Gonadotropin Promotes Tumor Invasion and Predicts Poor Prognosis of Early-Stage Colorectal Cancer

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Jiali Li

2018-01-01

Full Text Available Background/Aims: It is well established that many non-trophoblastic tumors secrete HCG (human chorionic gonadotropin and that such secretion is correlated with the poor prognosis of tumor patients. This study aims to analyze the correlation between β-HCG expression and outcome of colorectal cancer (CRC and understand its role in CRC pathology Methods: We detected the mRNA and protein expression of β-HCG in human CRC tissues with RT-qPCR and immunohistochemistry, and we compared the clinical-pathological characteristics, prognosis and progression between the β-HCG positive and negative groups. We also generated CRC cell lines with β-HCG over-expression as well as β-HCG stable knockout, and evaluated cell function and mechanism in vitro and in vivo. Results: Fifty out of 136 CRC patients (37% expressed β-HCG at the invasive front. Clinical-pathological data showed that β-HCG was positively correlated with Dukes staging (P=0.031 and lymph node metastasis (P=0.012. Survival analysis suggested that the patients with high expression of β-HCG had poorer prognosis than those with low β-HCG expression (P=0.0289. β-HCG expression level was also positively correlated with tumor invasion in early-stage CRC patient tissues (P=0.0227. Additionally β-HCG promoted the migration and invasion of CRC in vitro and in vivo but had no effect on the proliferation of tumor cells. Conclusion: Our study demonstrated that β-HCG was ectopically expressed in the CRC patients and its high expression correlated with poor prognosis of early-stage CRC. Additionally it worked as an oncogene that promotes the migration and invasion of CRC by epithelial-mesenchymal transition (EMT.

Comparison of Knoop and Vickers surface microhardness and transverse microradiography for the study of early caries lesion formation in human and bovine enamel.

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Lippert, F; Lynch, R J M

2014-07-01

The aims of the present laboratory study were twofold: a) to investigate the suitability of Knoop and Vickers surface microhardness (SMH) in comparison to transverse microradiography (TMR) to investigate early enamel caries lesion formation; b) to compare the kinetics of caries lesion initiation and progression between human and bovine enamel. Specimens (90×bovine and 90×human enamel) were divided into six groups (demineralization times of 8/16/24/32/40/48h) of 15 per enamel type and demineralized using a partially saturated lactic acid solution. SMH was measured before and after demineralization and changes in indentation length (ΔIL) calculated. Lesions were characterized using TMR. Data were analyzed (two-way ANOVA) and Pearson correlation coefficients calculated. ΔIL increased with increasing demineralization times but plateaued after 40h, whereas lesion depth (L) and integrated mineral loss (ΔZ) increased almost linearly throughout. No differences between Knoop and Vickers SMH in their ability to measure enamel demineralization were observed as both correlated strongly. Overall, ΔIL correlated strongly with ΔZ and L but only moderately with the degree of surface zone mineralization, whereas ΔZ and L correlated strongly. Bovine demineralized faster than human enamel (all techniques). Lesions in bovine formed faster than in human enamel, although the resulting lesions were almost indistinguishable in their mineral distribution characteristics. Early caries lesion demineralization can be sufficiently studied by SMH, but its limitations on the assessment of the mineral status of more demineralized lesions must be considered. Ideally, complementary techniques to assess changes in both physical and chemical lesion characteristics would be employed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue

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K.P. Nickerson

2018-05-01

Full Text Available Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples and “mini-guts,” organoids grown from intestinal tissue taken from biopsy specimens. We analyzed gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. This work adds novel information regarding S. Typhi infection pathogenesis in humans, by replicating work shown in traditional cell models, and providing new data that can be applied to future vaccine development strategies. Keywords: Typhoid fever, Salmonella, Snapwell™ system, Human tissue, Terminal ileum, Immune system, Innate immunity, Immune evasion, Host-pathogen interaction, Vaccine development, Intestinal organoids, Organoid monolayer

The development of functional network organization in early childhood and early adolescence: A resting-state fNIRS study

OpenAIRE

Lin Cai; Qi Dong; Haijing Niu

2018-01-01

Early childhood (7–8 years old) and early adolescence (11–12 years old) constitute two landmark developmental stages that comprise considerable changes in neural cognition. However, very limited information from functional neuroimaging studies exists on the functional topological configuration of the human brain during specific developmental periods. In the present study, we utilized continuous resting-state functional near-infrared spectroscopy (rs-fNIRS) imaging data to examine topological ...

3 dimensional modelling of early human brain development using optical projection tomography

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Strachan Tom

2004-08-01

is visible within the developing nervous system at a minimum resolution of ~20 μm and 3D anatomical and gene expression domains can be defined and visualised successfully. The OPT models and accompanying technologies for manipulating them provide a powerful approach to visualising and analysing gene expression and morphology during early human brain development.

The Human Cytomegalovirus Major Immediate-Early Proteins as Antagonists of Intrinsic and Innate Antiviral Host Responses

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Michael Nevels

2009-11-01

Full Text Available The major immediate-early (IE gene of human cytomegalovirus (CMV is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the 72-kDa IE1 and the 86-kDa IE2 nuclear phosphoproteins are the most abundant and important. Both proteins have long been recognized as promiscuous transcriptional regulators. More recently, a critical role of the IE1 and IE2 proteins in counteracting nonadaptive host cell defense mechanisms has been revealed. In this review we will briefly summarize the available literature on IE1- and IE2-dependent mechanisms contributing to CMV evasion from intrinsic and innate immune responses.

Agerinia smithorum sp. nov., a new early Eocene primate from the Iberian Peninsula.

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Femenias-Gual, Joan; Minwer-Barakat, Raef; Marigó, Judit; Moyà-Solà, Salvador

2016-09-01

The new species Agerinia smithorum (Adapiformes, Primates) from the early Eocene of the Iberian Peninsula is erected in this work. An emended diagnosis of the genus is provided, together with a broad description of the new species and comparisons with other samples assigned to Agerinia and other similar medium-sized cercamoniines. The new species is based on the most complete specimen of this genus published to date, a mandible preserving the alveoli of the canine and P1 , the roots of the P2 and all teeth from P3 to M3 . It was found in Casa Retjo-1, a new early Eocene locality from Northeastern Spain. The studied specimen is clearly distinguishable from other cercamoniines such as Periconodon, Darwinius, and Donrussellia, but very similar to Agerinia roselli, especially in the similar height of P3 and P4 and the general morphology of the molars, therefore allowing the allocation to the same genus. However, it is undoubtedly distinct from A. roselli, having a less molarized P4 and showing a larger paraconid in the M1 and a tiny one in the M2 , among other differences. The body mass of A. smithorum has also been estimated, ranging from 652 to 724 g, similar to that of A. roselli. The primitive traits shown by A. smithorum (moderately molarized P4 , large paraconid in the M1 and small but distinct in the M2 ) suggest that it could be the ancestor of A. roselli. © 2016 Wiley Periodicals, Inc.

Metabolism of 4-/sup 14/C-dehydroepiandrosterone and 4-/sup 14/C-4-Androstene-3, 17-dione by isolated cells of early human placenta

Energy Technology Data Exchange (ETDEWEB)

Dziadkowiec, I; Czarnik, Z; Rembiesa, R [Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Krakow

1977-03-01

The preparation of isolated cells was used for the study of the metabolism of 4-/sup 14/C-dehydroepiandrosterone and 4-/sup 14/C-4-androstene-3,17-dione in early human placenta. Free cell suspension converted dehydroepiandrosterone and 4-androstene-3,17-dione into estrone, estradiol-17..beta.., 4-androstene-3,17-dione and testosterone.

Determinism and randomness in the evolution of introns and sine inserts in mouse and human mitochondrial solute carrier and cytokine receptor genes.

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Cianciulli, Antonia; Calvello, Rosa; Panaro, Maria A

2015-04-01

In the homologous genes studied, the exons and introns alternated in the same order in mouse and human. We studied, in both species: corresponding short segments of introns, whole corresponding introns and complete homologous genes. We considered the total number of nucleotides and the number and orientation of the SINE inserts. Comparisons of mouse and human data series showed that at the level of individual relatively short segments of intronic sequences the stochastic variability prevails in the local structuring, but at higher levels of organization a deterministic component emerges, conserved in mouse and human during the divergent evolution, despite the ample re-editing of the intronic sequences and the fact that processes such as SINE spread had taken place in an independent way in the two species. Intron conservation is negatively correlated with the SINE occupancy, suggesting that virus inserts interfere with the conservation of the sequences inherited from the common ancestor. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ancient humans and the origin of modern humans.

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Kelso, Janet; Prüfer, Kay

2014-12-01

Recent advances in sequencing technologies and molecular methods have facilitated the sequencing of DNA from ancient human remains which has, in turn, provided unprecedented insight into human history. Within the past 4 years the genomes of Neandertals and Denisovans, as well as the genomes of at least two early modern humans, have been sequenced. These sequences showed that there have been several episodes of admixture between modern and archaic groups; including admixture from Neandertals into modern human populations outside of Africa, and admixture from Denisovans into modern human populations in Oceania. Recent results indicate that some of these introgressed regions may have been advantageous for modern humans as they expanded into new regions outside of Africa. Copyright © 2014. Published by Elsevier Ltd.

Barium distributions in teeth reveal early-life dietary transitions in primates.

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Austin, Christine; Smith, Tanya M; Bradman, Asa; Hinde, Katie; Joannes-Boyau, Renaud; Bishop, David; Hare, Dominic J; Doble, Philip; Eskenazi, Brenda; Arora, Manish

2013-06-13

Early-life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth. Uncovering early-life dietary history in fossils is hampered by the absence of prospectively validated biomarkers that are not modified during fossilization. Here we show that large dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother's milk through the weaning process. We also document dietary transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, indicating an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history.

Barium distributions in teeth reveal early life dietary transitions in primates

Science.gov (United States)

Austin, Christine; Smith, Tanya M.; Bradman, Asa; Hinde, Katie; Joannes-Boyau, Renaud; Bishop, David; Hare, Dominic J.; Doble, Philip; Eskenazi, Brenda; Arora, Manish

2013-01-01

Early life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations1,2. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth3. Uncovering early life dietary history in fossils is hampered by the absence of prospectively-validated biomarkers that are not modified during fossilisation4. Here we show that major dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively-recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother’s milk and through the weaning process. We also document transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, suggesting an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history. PMID:23698370

Colloquium paper: uniquely human evolution of sialic acid genetics and biology.

Science.gov (United States)

Varki, Ajit

2010-05-11

Darwinian evolution of humans from our common ancestors with nonhuman primates involved many gene-environment interactions at the population level, and the resulting human-specific genetic changes must contribute to the "Human Condition." Recent data indicate that the biology of sialic acids (which directly involves less than 60 genes) shows more than 10 uniquely human genetic changes in comparison with our closest evolutionary relatives. Known outcomes are tissue-specific changes in abundant cell-surface glycans, changes in specificity and/or expression of multiple proteins that recognize these glycans, and novel pathogen regimes. Specific events include Alu-mediated inactivation of the CMAH gene, resulting in loss of synthesis of the Sia N-glycolylneuraminic acid (Neu5Gc) and increase in expression of the precursor N-acetylneuraminic acid (Neu5Ac); increased expression of alpha2-6-linked Sias (likely because of changed expression of ST6GALI); and multiple changes in SIGLEC genes encoding Sia-recognizing Ig-like lectins (Siglecs). The last includes binding specificity changes (in Siglecs -5, -7, -9, -11, and -12); expression pattern changes (in Siglecs -1, -5, -6, and -11); gene conversion (SIGLEC11); and deletion or pseudogenization (SIGLEC13, SIGLEC14, and SIGLEC16). A nongenetic outcome of the CMAH mutation is human metabolic incorporation of foreign dietary Neu5Gc, in the face of circulating anti-Neu5Gc antibodies, generating a novel "xeno-auto-antigen" situation. Taken together, these data suggest that both the genes associated with Sia biology and the related impacts of the environment comprise a relative "hot spot" of genetic and physiological changes in human evolution, with implications for uniquely human features both in health and disease.

Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells

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Qi, Yuchen; Zhang, Xin-Jun; Renier, Nicolas; Wu, Zhuhao; Atkin, Talia; Sun, Ziyi; Ozair, M. Zeeshan; Tchieu, Jason; Zimmer, Bastian; Fattahi, Faranak; Ganat, Yosif; Azevedo, Ricardo; Zeltner, Nadja; Brivanlou, Ali H.; Karayiorgou, Maria; Gogos, Joseph; Tomishima, Mark; Tessier-Lavigne, Marc; Shi, Song-Hai; Studer, Lorenz

2017-01-01

Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions for the rapid differentiation of hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of 6 pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 days of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders. PMID:28112759

An alternative method for assessing early mortality in contemporary populations.

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Wiley, A S; Pike, I L

1998-11-01

Biological anthropologists are interested in a population's early mortality rates for a variety of reasons. Early mortality (infant or juvenile) is of obvious importance to those interested in demography, but early mortality statistics are useful for life history analysis, paleodemography, and human adaptability studies, among others. In general, the form of mortality statistics is derived from demography, where chronological age is the gold standard for statistical calculation and comparison. However, there are numerous problems associated with the collection, analysis, and interpretation of early mortality statistics based on age, particularly for anthropological research, which is often conducted in small or non-calendrical-age numerate populations. The infant mortality rate (IMR), for example, is notoriously difficult to determine in populations where accurate accounting of age is not routine, and yet it is widely used in demography, public health, medicine, and social science research. Here we offer an alternative to age-based early mortality statistics that makes use of human biologists' interest in, and skill at, assessing human growth and development. Our proposal is to use developmental stages of juveniles instead of relying exclusively on age as the basis for mortality statistics. Death or survival according to a developmental stage (such as crawling or weaning) may provide more accurate data that are also more closely related to the cause of death. Developmental stages have the added advantage of putting infants and children back at the center of the discussion of early mortality by focusing on their activities in relation to their environment. A case study from the Turkana population of Kenya illustrates the use of developmental stages in describing early mortality.

Putative alternative polyadenylation (APA) events in the early interaction of Salmonella enterica Typhimurium and human host cells.

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Afonso-Grunz, Fabian

2015-12-01

The immune response of epithelial cells upon infection is mediated by changing activity levels of a variety of proteins along with changes in mRNA, and also ncRNA abundance. Alternative polyadenylation (APA) represents a mechanism that diversifies gene expression similar to alternative splicing. T-cell activation, neuronal activity, development and several human diseases including viral infections involve APA, but at present it remains unclear if this mechanism is also implicated in the response to bacterial infections. Our recently published study of interacting Salmonella enterica Typhimurium and human host cells includes genome-wide expression profiles of human epithelial cells prior and subsequent to infection with the invasive pathogen. The generated dataset (GEO accession number: GSE61730) covers several points of time post infection, and one of these interaction stages was additionally profiled with MACE-based dual 3'Seq, which allows for identification of polyadenylation (PA) sites. The present study features the polyadenylation landscape in early interacting cells based on this data, and provides a comparison of the identified PA sites with those of a corresponding 3P-Seq dataset of non-interacting cells. Differential PA site usage of FTL , PRDX1 and VAPA results in transcription of mRNA isoforms with distinct sets of miRNA and protein binding sites that influence processing, localization, stability, and translation of the respective mRNA. APA of these candidate genes consequently harbors the potential to modulate the host cell response to bacterial infection.

Putative alternative polyadenylation (APA events in the early interaction of Salmonella enterica Typhimurium and human host cells

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Fabian Afonso-Grunz

2015-12-01

Full Text Available The immune response of epithelial cells upon infection is mediated by changing activity levels of a variety of proteins along with changes in mRNA, and also ncRNA abundance. Alternative polyadenylation (APA represents a mechanism that diversifies gene expression similar to alternative splicing. T-cell activation, neuronal activity, development and several human diseases including viral infections involve APA, but at present it remains unclear if this mechanism is also implicated in the response to bacterial infections. Our recently published study of interacting Salmonella enterica Typhimurium and human host cells includes genome-wide expression profiles of human epithelial cells prior and subsequent to infection with the invasive pathogen. The generated dataset (GEO accession number: GSE61730 covers several points of time post infection, and one of these interaction stages was additionally profiled with MACE-based dual 3'Seq, which allows for identification of polyadenylation (PA sites. The present study features the polyadenylation landscape in early interacting cells based on this data, and provides a comparison of the identified PA sites with those of a corresponding 3P-Seq dataset of non-interacting cells. Differential PA site usage of FTL, PRDX1 and VAPA results in transcription of mRNA isoforms with distinct sets of miRNA and protein binding sites that influence processing, localization, stability, and translation of the respective mRNA. APA of these candidate genes consequently harbors the potential to modulate the host cell response to bacterial infection.

Alu repeats as markers for human population genetics

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Batzer, M.A.; Alegria-Hartman, M. [Lawrence Livermore National Lab., CA (United States); Bazan, H. [Louisiana State Univ., New Orleans, LA (United States). Medical Center] [and others

1993-09-01

The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 97.9% nucleotide identity with each other and an average of 98.9% nucleotide identity with the HS subfamily consensus sequence. HS Alu family members are thought to be derived from a single source ``master`` gene, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 in. and 3 in. unique flanking DNA sequences from each HS Alu that allows the locus to be assayed for the presence or absence of an Alu repeat. Individual HS Alu sequences were found to be either monomorphic or dimorphic for the presence or absence of each repeat. The monomorphic HS Alu family members inserted in the human genome after the human/great ape divergence (which is thought to have occurred 4--6 million years ago), but before the radiation of modem man. The dimorphic HS Alu sequences inserted in the human genome after the radiation of modem man (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project as well. HS Alu family member insertion dimorphism differs from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) because individuals share HS Alu family member insertions based upon identity by descent from a common ancestor as a result of a single event which occurred one time within the human population. The VNTR and RFLP polymorphisms may arise multiple times within a population and are identical by state only.

Early life stress paradigms in rodents: potential animal models of depression?

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Schmidt, Mathias V; Wang, Xiao-Dong; Meijer, Onno C

2011-03-01

While human depressive illness is indeed uniquely human, many of its symptoms may be modeled in rodents. Based on human etiology, the assumption has been made that depression-like behavior in rats and mice can be modulated by some of the powerful early life programming effects that are known to occur after manipulations in the first weeks of life. Here we review the evidence that is available in literature for early life manipulation as risk factors for the development of depression-like symptoms such as anhedonia, passive coping strategies, and neuroendocrine changes. Early life paradigms that were evaluated include early handling, separation, and deprivation protocols, as well as enriched and impoverished environments. We have also included a small number of stress-related pharmacological models. We find that for most early life paradigms per se, the actual validity for depression is limited. A number of models have not been tested with respect to classical depression-like behaviors, while in many cases, the outcome of such experiments is variable and depends on strain and additional factors. Because programming effects confer vulnerability rather than disease, a number of paradigms hold promise for usefulness in depression research, in combination with the proper genetic background and adult life challenges.

A review of studies on community based early warning systems

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Margaret Macherera

2016-04-01

Full Text Available Community-based early warning systems involve community driven collection and analysis of information that enable warning messages to help a community to react to a hazard and reduce the resulting loss or harm. Most early warning systems are designed at the national or global level. Local communities’ capacity to predict weather conditions using indigenous knowledge has been demonstrated in studies focusing on climate change and agriculture in some African countries. This review was motivated by successes made in non-disease specific community-based early warning systems with a view to identify opportunities for developing similar systems for malaria. This article reviewed the existing community-based early warning systems documented in literature. The types of disasters that are addressed by these systems and the methodologies utilised in the development of the systems were identified. The review showed that most of the documented community-based early warning systems focus on natural disasters such as floods, drought, and landslides. Community-based early warning systems for human diseases are very few, even though such systems exist at national and regional and global levels. There is a clear gap in terms of community-based malaria early warning systems. The methodologies for the development of the community-based early warning systems reviewed mainly derive from the four elements of early warning systems; namely risk knowledge, monitoring, warning communication and response capability. The review indicated the need for the development of community based early warning systems for human diseases. Keywords: community; early warning; disaster; hazards

Odour discrimination and identification are improved in early blindness.

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Cuevas, Isabel; Plaza, Paula; Rombaux, Philippe; De Volder, Anne G; Renier, Laurent

2009-12-01

Previous studies showed that early blind humans develop superior abilities in the use of their remaining senses, hypothetically due to a functional reorganization of the deprived visual brain areas. While auditory and tactile functions have been investigated for long, little is known about the effects of early visual deprivation on olfactory processing. However, blind humans make an extensive use of olfactory information in their daily life. Here we investigated olfactory discrimination and identification abilities in early blind subjects and age-matched sighted controls. Three levels of cuing were used in the identification task, i.e., free-identification (no cue), categorization (semantic cues) and multiple choice (semantic and phonological cues). Early blind subjects significantly outperformed the controls in odour discrimination, free-identification and categorization. In addition, the larger group difference was observed in the free-identification as compared to the categorization and the multiple choice conditions. This indicated that a better access to the semantic information from odour perception accounted for part of the improved olfactory performances in odour identification in the blind. We concluded that early blind subjects have both improved perceptual abilities and a better access to the information stored in semantic memory than sighted subjects.

Early and Periodic Screening, Diagnosis and Treatment

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U.S. Department of Health & Human Services — The Early and Periodic Screening, Diagnostic and Treatment (EPSDT) benefit provides comprehensive and preventive health care services for children under age 21 who...

Lutein concentration in human milk during early lactation and its relationship with dietary lutein intake.

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Cena, Hellas; Castellazzi, Anna Maria; Pietri, Amedeo; Roggi, Carla; Turconi, Giovanna

2009-10-01

The present study aimed to estimate the lutein concentration in human milk during early lactation and its relationship with dietary lutein intake measured through the administration of a short FFQ. A cross-sectional study in which an FFQ was administered twice: on day 3 (T0) and day 30 (T1) postpartum; meanwhile two breast milk samples were collected. Maternal plasma samples were obtained at T0. The comparison of dietary lutein intakes and likewise lutein concentrations in breast milk at T0 and T1 were analysed with Student's t test. Pearson's correlation coefficient was used to determine the association between dietary lutein intake and lutein concentration in milk and plasma, respectively, as well as the correlation between breast milk and plasma lutein concentrations at T0. Pavia, northern Italy. Twenty-one pregnant women, age range 24-42 years, were recruited during their last trimester on a voluntary basis. Both breast milk and plasma lutein concentrations were significantly correlated with dietary lutein intake (r = 0.86, P = 0.0001 and r = 0.94, P = 0.0001, respectively). There was a clear significant correlation between milk and plasma lutein concentrations (r = 0.87, P = 0.0001). Mature milk lutein concentration, although significantly reduced at T1 (P lutein intake (r = 0.82, P = 0.0001). Even though milk lutein concentration decreased during early lactation, it remained significantly correlated with daily lutein intake. Therefore, while awaiting further research, dietary recommendations advising intake of fresh fruit and vegetables rich in lutein, throughout the whole duration of pregnancy and lactation, are extremely useful.

Cytoarchitecture, probability maps and functions of the human frontal pole.

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Bludau, S; Eickhoff, S B; Mohlberg, H; Caspers, S; Laird, A R; Fox, P T; Schleicher, A; Zilles, K; Amunts, K

2014-06-01

The frontal pole has more expanded than any other part in the human brain as compared to our ancestors. It plays an important role for specifically human behavior and cognitive abilities, e.g. action selection (Kovach et al., 2012). Evidence about divergent functions of its medial and lateral part has been provided, both in the healthy brain and in psychiatric disorders. The anatomical correlates of such functional segregation, however, are still unknown due to a lack of stereotaxic, microstructural maps obtained in a representative sample of brains. Here we show that the human frontopolar cortex consists of two cytoarchitectonically and functionally distinct areas: lateral frontopolar area 1 (Fp1) and medial frontopolar area 2 (Fp2). Based on observer-independent mapping in serial, cell-body stained sections of 10 brains, three-dimensional, probabilistic maps of areas Fp1 and Fp2 were created. They show, for each position of the reference space, the probability with which each area was found in a particular voxel. Applying these maps as seed regions for a meta-analysis revealed that Fp1 and Fp2 differentially contribute to functional networks: Fp1 was involved in cognition, working memory and perception, whereas Fp2 was part of brain networks underlying affective processing and social cognition. The present study thus disclosed cortical correlates of a functional segregation of the human frontopolar cortex. The probabilistic maps provide a sound anatomical basis for interpreting neuroimaging data in the living human brain, and open new perspectives for analyzing structure-function relationships in the prefrontal cortex. The new data will also serve as a starting point for further comparative studies between human and non-human primate brains. This allows finding similarities and differences in the organizational principles of the frontal lobe during evolution as neurobiological basis for our behavior and cognitive abilities. Copyright © 2013 Elsevier Inc. All

Early life history and habitat ecology of estuarine fishes: responses to natural and human induced change

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Kenneth Able

2015-12-01

Full Text Available Our understanding of the early life history of fishes and their habitats has proceeded from basic natural history to ecology, but we often need to return to natural history to address deficiencies in conceptual and quantitative models of ecosystems. This understanding is further limited by the complex life history of fishes and the lack of appreciation of shifting baselines in estuaries. These inadequacies are especially evident when we try to address the effects of human influences, e.g. fishing, urbanization, and climate change. Often our baselines are inadequate or inaccurate. Our work has detected these along the coasts of the U.S. in extensive time series of larval fish ingress into estuaries, studies of the effects of urbanization, and responses to catastrophes such as the BP oil spill. Long-term monitoring, especially, continues to provide critical insights

Direct detection of early-stage cancers using circulating tumor DNA