Integration of ancient DNA with transdisciplinary dataset finds strong support for Inca resettlement in the south Peruvian coast

Ancient DNA (aDNA) analysis provides a powerful means of investigating human migration, social organization, and a plethora of other crucial questions about humanity’s past. Recently, specialists have suggested that the ideal research design involving aDNA would include multiple independent lines of evidence. In this paper, we adopt a transdisciplinary approach integrating aDNA with archaeological, biogeochemical, and historical data to investigate six individuals found in two cemeteries that date to the Late Horizon (1400 to 1532 CE) and Colonial (1532 to 1825 CE) periods in the Chincha Valley of southern Peru. Genomic analyses indicate that these individuals are genetically most similar to ancient and present-day populations from the north Peruvian coast located several hundred kilometers away. These genomic data are consistent with 16th century written records as well as ceramic, textile, and isotopic data. These results provide some of the strongest evidence yet of state-sponsored resettlement in the pre-Colonial Andes. This study highlights the power of transdisciplinary research designs when using aDNA data and sets a methodological standard for investigating ancient mobility in complex societies

The phenotype of floating-harbor syndrome:clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background\ud Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome.\ud \ud Methods and results\ud Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations.\ud \ud Conclusions\ud This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.The authors would like to thank the families for their cooperation and permission to publish these findings. SdM would like to thank Barto Otten. Funding was provided by the Government of Canada through Genome Canada, the Canadian Institutes of Health Research (CIHR) and the Ontario Genomics Institute (OGI-049), by Genome Québec and Genome British Columbia, and the Manton Center for Orphan Disease Research at Children’s Hospital Boston. KMB is supported by a Clinical Investigatorship Award from the CIHR Institute of Genetics. AD is supported by NIH grant K23HD073351. BBAdV and HGB were financially supported by the AnEUploidy project (LSHG-CT-2006-37627). This work was selected for study by the FORGE Canada Steering Committee, which consists of K. Boycott (University of Ottawa), J. Friedman (University of British Columbia), J. Michaud (University of Montreal), F. Bernier (University of Calgary), M. Brudno (University of Toronto), B. Fernandez (Memorial University), B. Knoppers (McGill University), M. Samuels (Université de Montréal), and S. Scherer (University of Toronto). We thank the Galliera Genetic Bank - “Telethon Genetic Biobank Network” supported by Italian Telethon grants (project no. GTB07001) for providing us with specimens

The phenotype of Floating-Harbor syndrome: Clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results. Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from

Nitric Oxide: Perspectives and Emerging Studies of a Well Known Cytotoxin

The free radical nitric oxide (NO•) is known to play a dual role in human physiology and pathophysiology. At low levels, NO• can protect cells; however, at higher levels, NO• is a known cytotoxin, having been implicated in tumor angiogenesis and progression. While the majority of research devoted to understanding the role of NO• in cancer has to date been tissue-specific, we herein review underlying commonalities of NO• which may well exist among tumors arising from a variety of different sites. We also discuss the role of NO• in human physiology and pathophysiology, including the very important relationship between NO• and the glutathione-transferases, a class of protective enzymes involved in cellular protection. The emerging role of NO• in three main areas of epigenetics—DNA methylation, microRNAs, and histone modifications—is then discussed. Finally, we describe the recent development of a model cell line system in which human tumor cell lines were adapted to high NO• (HNO) levels. We anticipate that these HNO cell lines will serve as a useful tool in the ongoing efforts to better understand the role of NO• in cancer

Molecular genetic analysis of podocyte genes in focal segmental glomerulosclerosis—a review

This review deals with podocyte proteins that play a significant role in the structure and function of the glomerular filter. Genetic linkage studies has identified several genes involved in the development of nephrotic syndrome and contributed to the understanding of the pathophysiology of glomerular proteinuria and/or focal segmental glomerulosclerosis. Here, we describe already well-characterized genetic diseases due to mutations in nephrin, podocin, CD2AP, alpha-actinin-4, WT1, and laminin β2 chain, as well as more recently identified genetic abnormalities in TRPC6, phospholipase C epsilon, and the proteins encoded by the mitochondrial genome. In addition, the role of the proteins which have shown to be important for the structure and functions by gene knockout studies in mice, are also discussed. Furthermore, some rare syndromes with glomerular involvement, in which molecular defects have been recently identified, are briefly described. In summary, this review updates the current knowledge of genetic causes of congenital and childhood nephrotic syndrome and provides new insights into mechanisms of glomerular dysfunction

Mortuary Practice, Imperial Conquest, and Sociopolitical Change in the Middle Chincha Valley, Peru (ca. AD 1200 – 1650)

This research explores the relationship between mortuary practice and sociopolitical change among a collection of communities incorporated into the Inca Empire. I conducted this work in the Chincha Valley of central Peru, an area controlled by a complex polity known as the Chincha Kingdom in the Late Intermediate Period, or LIP (AD 1000 – 1400). During the Late Horizon (AD 1400 – 1532), the Chincha Kingdom fell under the rule of the Inca Empire. In this study, I investigated a dense, well-preserved distribution of graves in the middle Chincha Valley. Using methods from archaeology, GIS, and Bayesian statistical modeling, I examined the nature and development of local mortuary practice in the mid-valley from the LIP to the Late Horizon and recorded over 500 well-preserved graves that cluster into 44 mortuary sites. These sites vary in layout and have two distinct grave types that differ in architecture and use: above-ground and subterranean graves (chullpas) and subterranean cists. Radiocarbon data indicate continuity, change, and innovation in tomb use and treatment of the dead through time. I argue that these diachronic mortuary patterns were products of negotiations among indigenous groups and the Inca. Mid-valley peoples manipulated the remains of their dead to produce new deceased persons before and during their incorporation into the Inca Empire. They dynamically reconfigured the ways relationships among the living and the deceased were performed, thereby transforming their sociopolitical landscape in the face of imperial conquest. This study provides support for a model of mortuary practice as an interface through which interactions between complex societies and expansionist empires occurred

The rise of native lordships at Pashash, A.D. 200–600, North Highlands of Ancash, Peru

This article examines the rise of native, segmentary lordships in the highlands of north-central Peru. It reports on new excavations and mapping at the seat of a prehispanic polity, Pashash (Recuay culture), a large hilltop center that developed after the collapse of Chavín civilization. Fieldwork revealed monumental constructions and two special activity contexts radiocarbon-dated to ca. a.d. 200–400: an offering area in a large palatial compound and a room-complex with chambers closed off and sealed with feasting refuse. Multiple lines of evidence help reconstruct a regional picture for the establishment of wealthy local elites. Cultural innovations explicitly link new leaders to roles in defense and warfare, economic production, and early burial cult within a high-status compound. The current data underscore a major break from earlier systems of authority and elite material culture, comprising an organizational pattern that was a precursor to the ethnic polities that predominated in later Andean prehistory