Gravity constraint in cell phenotypic determination

Distinct phenotypes emerge spontaneously when mammalian cells are cultured under microgravity conditions. Such finding is explained by the interplay among the intrinsic stochasticity, which, in turn, is successively ‘canalized’ and sustained by the activation of a specific gene regulatory network. However, when the two cell subsets are reseeded into a normal gravity field the two phenotypes collapse into one. Gravity constraints the system in adopting only one phenotype. Cell fate commitment is achieved through a de novo reshaping of the overall cell morphological and functional organization, and cannot be explained as a ‘selecting’ effect. Those findings highlight how constraints – acting as global order factors – drive cell specification and behavior. These data cast on doubt the current explanatory bottom-up, molecular based models

Before Kukulkán

This volume illuminates human lifeways in the northern Maya lowlands prior to the rise of Chichén Itzá. This period and area have been poorly understood on their own terms, obscured by scholarly focus on the central lowland Maya kingdoms. "Before Kukulkán" is anchored in three decades of interdisciplinary research at the Classic Maya capital of Yaxuná, located at a contentious crossroads of the northern Maya lowlands. Using bioarchaeology, mortuary archaeology, and culturally sensitive mainstream archaeology, the authors create an in-depth regional understanding while also laying out broader ways of learning about the Maya past. Part 1 examines ancient lifeways among the Maya at Yaxuná, while part 2 explores different meanings of dying and cycling at the settlement and beyond: ancestral practices, royal entombment and desecration, and human sacrifice. The authors close with a discussion of the last years of occupation at Yaxuná and the role of Chichén Itzá in the abandonment of this urban center. "Before Kukulkán" provides a cohesive synthesis of the evolving roles and collective identities of locals and foreigners at the settlement and their involvement in the region’s trajectory. Theoretically informed and contextualized discussions offer unique glimpses of everyday life and death in the socially fluid Maya city. These findings, in conjunction with other documented series of skeletal remains from this region, provide a nuanced picture of the social and biocultural dynamics that operated successfully for centuries before the arrival of the Itzá

Comparison of two ancient DNA extraction protocols for skeletal remains from tropical environments

Objectives The tropics harbor a large part of the world\u27s biodiversity and have a long history of human habitation. However, paleogenomics research in these climates has been constrained so far by poor ancient DNA yields. Here we compare the performance of two DNA extraction methods on ancient samples of teeth and petrous portions excavated from tropical and semi‐tropical sites in Tanzania, Mexico, and Puerto Rico (N = 12). Materials and Methods All samples were extracted twice, built into double‐stranded sequencing libraries, and shotgun sequenced on the Illumina HiSeq 2500. The first extraction protocol, Method D, was previously designed for recovery of ultrashort DNA fragments from skeletal remains. The second, Method H, modifies the first by adding an initial EDTA wash and an extended digestion and decalcification step. Results No significant difference was found in overall ancient DNA yields or post‐mortem damage patterns recovered from samples extracted with either method, irrespective of tissue type. However, Method H samples had higher endogenous content and more mapped reads after quality‐filtering, but also higher clonality. In contrast, samples extracted with Method D had shorter average DNA fragments. Discussion Both methods successfully recovered endogenous ancient DNA. But, since surviving DNA in ancient or historic remains from tropical contexts is extremely fragmented, our results suggest that Method D is the optimal choice for working with samples from warm and humid environments. Additional optimization of extraction conditions and further testing of Method H with different types of samples may allow for improvement of this protocol in the future

The PI3K/AKT pathway is activated by HGF in NT2D1 non-seminoma cells and has a role in the modulation of their malignant behavior

Overactivation of the c-MET/HGF system is a feature of many cancers. We previously reported that type II testicular germ cell tumor (TGCT) cells express the c-MET receptor, forming non-seminomatous lesions that are more positive compared with seminomatous ones. Notably, we also demonstrated that NT2D1 non-seminomatous cells (derived from an embryonal carcinoma lesion) increase their proliferation, migration, and invasion in response to HGF. Herein, we report that HGF immunoreactivity is more evident in the microenvironment of embryonal carcinoma biopsies with respect to seminomatous ones, indicating a tumor-dependent modulation of the testicular niche. PI3K/AKT is one of the signaling pathways triggered by HGF through the c-MET activation cascade. Herein, we demonstrated that phospho-AKT increases in NT2D1 cells after HGF stimulation. Moreover, we found that this pathway is involved in HGF-dependent NT2D1 cell proliferation, migration, and invasion, since the co-administration of the PI3K inhibitor LY294002 together with HGF abrogates these responses. Notably, the inhibition of endogenous PI3K affects collective cell migration but does not influence proliferation or chemotactic activity. Surprisingly, LY294002 administered without the co-administration of HGF increases cell invasion at levels comparable to the HGF-administered samples. This paradoxical result highlights the role of the testicular microenvironment in the modulation of cellular responses and stimulates the study of the testicular secretome in cancer lesions

A genetic history of the pre-contact Caribbean

Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago1,2,3. Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work4, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500–1,500 and a maximum of 1,530–8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large5,6. Confirming a small and interconnected Ceramic Age population7, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world1,8.This work was supported by a grant from the National Geographic Society to M. Pateman to facilitate analysis of skeletal material from The Bahamas and by a grant from the Italian ‘Ministry of Foreign Affairs and International Cooperation’ (Italian archaeological, anthropological and ethnological missions abroad, DGPSP Ufficio VI). D.R. was funded by NSF HOMINID grant BCS-1032255, NIH (NIGMS) grant GM100233, the Paul Allen Foundation, the John Templeton Foundation grant 61220 and the Howard Hughes Medical Institute.Peer reviewe

Mortuary Pathways and Ritual Meanings Related to Maya Human Bone Deposits in Subterranean Contexts

The ancient Maya regarded dry caves, crevices, rockshelters, and cenotes as sacred spaces and accesses to the earthen womb of the cosmos, thresholds through which the living communicated with natural powers. To test different hypotheses for context-specific or diverse mortuary use of Maya caves, cenotes, crevices, and rockshelters, we describe sex and age profiles, note the presence and types of cranial modifications, compare patterns of posthumous body manipulation, and reconstruct mortuary pathways in 35 human bone assemblages from the Maya realm, spanning the Preclassic to Colonial/Modern times, the latter represented by the Lacandon Maya in the forest of Chiapas. Combining anthropological, taphonomic, and contextual data sets, we test the hypothesis that different ritual practices and associated mortuary behaviors may be recognized by profiling burial populations from caves, crevices, rockshelters, and cenotes, and both wet and dry cave deposits. The documented scope of mortuary practices involving “hidden places” indicates that every single context went through its own history of use and reuse, regardless of the specific type of context. These results suggest the need for a reevaluation of the generalized roles of such sites as human depositories and for the application of more precise techniques in the recovery and subsequent analyses of human deposits directly related to access to the underworld

Italian Populations During the Copper Age: Assessment of Biological Affinities Through Morphological Dental Traits

The Copper Age (3rd millennium BC) was characterized by considerable socioeconomic transformations and coincided with the discovery of metallurgy. In this study we reconstruct the peopling of Italy during this period on the basis of dental morphology traits. Dental remains from 41 sites throughout Italy were analyzed; only three of the sites (Laterza and two from Sicily) span from the late Copper Age to the early Bronze Age. To work with adequate samples, we pooled the collections into nine geographically and culturally homogeneous groups. Dental morphological traits were scored on 8,891 teeth from 1,302 individuals using the ASUDAS scale. The correlation between the mean measure of divergence and geographic distances (calculated as air distances) was computed. Multidimensional scaling with the minimum spanning tree and maximum-likelihood methods was applied to assess the relationships between groups. The results revealed a substantial genetic homogeneity among the populations throughout the Italian peninsula during the Copper Age with the exception of Sardinia, which tends to diverge from the continental samples. Phenetic and geographic distances correlate highly significantly only when the southern samples from Sicily and Laterza are removed from the analysis, which indicates that these groups may have experienced genetic admixture with external populations