A Bayesian approach to linking archaeological, paleoenvironmental and documentary datasets relating to the settlement of Iceland (Landnám)

YesIcelandic settlement (Landnám) period farmsteads offer opportunities to explore the nature and timing of anthropogenic activities and environmental impacts of the first Holocene farming communities. We employ Bayesian statistical modelling of archaeological, paleoenvironmental and documentary datasets to present a framework for improving chronological robustness of archaeological events. Specifically, we discuss events relevant to the farm Hrísbrú, an initial and complex settlement site in southwest Iceland. We demonstrate that tephra layers are key in constraining reliable chronologies, especially when combined with related datasets and treated in a Bayesian framework. The work presented here confirms earlier interpretations of the chronology of the site while providing increased confidence in the robustness of the chronology. Most importantly, integrated modelling of AMS radiocarbon dates on Hordeum vulgare grains, palynological data, documented evidence from textual records and typologically diagnostic artefacts yield increased dating reliability. The analysis has also shown that AMS radiocarbon dates on bone collagen need further scrutiny. Specifically for the Hrísbrú farm, first anthropogenic footprint palynomorph taxa are estimated to around AD 830–881 (at 95.4% confidence level), most likely before the tephra fall out of AD 877 ± 1 (the Landnám tephra layer), demonstrating the use of arable fields before the first known structures were built at Hrísbrú (AD 874–951) and prior to the conventionally accepted date of the settlement of Iceland. Finally, we highlight the importance of considering multidisciplinary factors for other archaeological and paleoecological studies of early farming communities of previously uninhabited island areas

Prevalence of 22q11.2 microdeletion in 146 patients with cardiac malformation in a referral hospital of North India

<p>Abstract</p> <p>Background</p> <p>The 22q11.2 microdeletion syndrome is a common condition that is associated with cardiac as well as extra-cardiac manifestations. Its prevalence and manifestations from north India has not been reported. This study was designed to determine the prevalence and ability of clinical criteria to predict 22q11.2 microdeletion.</p> <p>Methods</p> <p>A total of 146 cases of cardiac malformation requiring tertiary care at a teaching hospital were prospectively screened for 22q11.2 microdeletion using fluorescence in situ hybridization test. Detailed clinical information was obtained as per guidelines of Tobias, <it>et al </it>(1999).</p> <p>Results</p> <p>Nine out of 146 patients (6.16%) was found to have 22q11.2 microdeletion. All the positive patients showed the presence of extra-cardiac features of 22q11.2 microdeletion syndrome. None of the cases with isolated cardiac defect were positive for microdeletion.</p> <p>Conclusions</p> <p>It seems that 22q11.2 microdeletion syndrome is over-suspected in children with isolated congenital heart defects. Screening for 22q11.2 microdeletion should be considered in those cardiac malformation cases which have extra-cardiac manifestations in the form of facial dysmorphism and hypocalcaemia.</p

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Fabrication of ATLAS pixel detector prototypes at IRST

We report on the development of a fabrication technology for n-on-n silicon pixel detectors oriented to the ATLAS experiment at LHC. The main processing issues and some selected results from the electrical characterization of detector prototypes and related test structures are presented and discussed. (5 refs)