Unexpected Relationships and Inbreeding in HapMap Phase III Populations

Correct annotation of the genetic relationships between samples is essential for population genomic studies, which could be biased by errors or omissions. To this end, we used identity-by-state (IBS) and identity-by-descent (IBD) methods to assess genetic relatedness of individuals within HapMap phase III data. We analyzed data from 1,397 individuals across 11 ethnic populations. Our results support previous studies (Pemberton et al., 2010; Kyriazopoulou-Panagiotopoulou et al., 2011) assessing unknown relatedness present within this population. Additionally, we present evidence for 1,657 novel pairwise relationships across 9 populations. Surprisingly, significant Cotterman''s coefficients of relatedness K1 (IBD1) values were detected between pairs of known parents. Furthermore, significant K2 (IBD2) values were detected in 32 previously annotated parent-child relationships. Consistent with a hypothesis of inbreeding, regions of homozygosity (ROH) were identified in the offspring of related parents, of which a subset overlapped those reported in previous studies (Gibson et al. 2010; Johnson et al. 2011). In total, we inferred 28 inbred individuals with ROH that overlapped areas of relatedness between the parents and/or IBD2 sharing at a different genomic locus between a child and a parent. Finally, 8 previously annotated parent-child relationships had unexpected K0 (IBD0) values (resulting from a chromosomal abnormality or genotype error), and 10 previously annotated second-degree relationships along with 38 other novel pairwise relationships had unexpected IBD2 (indicating two separate paths of recent ancestry). These newly described types of relatedness may impact the outcome of previous studies and should inform the design of future studies relying on the HapMap Phase III resource.     

Geology of the Early Arikareean Sharps Formation on the Pine Ridge Indian Reservation and Surrounding Areas of South Dakota and Nebraska

Based on geologic mapping, measured sections, and lithologic correlations, the local features of the upper and lower type areas of the Early Arikareean (30.8–20.6 million years ago) Sharps Formation are revised and correlated. The Sharps Formation above the basal Rockyford Member is divided into two members of distinct lithotypes. The upper 233 feet of massive siltstones and sandy siltstones is named the Gooseneck Road Member. The middle member, 161 feet of eolian volcaniclastic siltstones with fluvially reworked volcaniclastic lenses and sandy siltstone sheets, is named the Wolff Camp Member. An ashey zone at the base of the Sharps Formation is described and defined as the Rockyford Ash Zone (RAZ) in the same stratigraphic position as the Nonpareil Ash Zone (NPAZ) in Nebraska. Widespread marker beds of fresh water limestones at 130 feet above the base of the Sharps Formation and a widespread reddish-brown clayey siltstone at 165 feet above the base of the Sharps Formation are described. The Brown Siltstone Beds of Nebraska are shown to be a southern correlative of the Wolff Camp Member and the Rockyford Member of the Sharps Formation. Early attempts to correlate strata in the Great Plains were slow in developing. Recognition of the implications of the paleomagnetic and lithologic correlations of this paper will provide an added datum assisting researchers in future biostratigraphic studies. Based on similar lithologies, the Sharps Formation, currently assigned to the Arikaree Group, should be reassigned to the White River Group.     

An accurate definition of the status of inactive hepatitis B virus carrier by a combination of biomarkers (FibroTest-ActiTest) and viral load

Background

The combination of transaminases (ALT), biopsy, HBeAg and viral load have classically defined the inactive status of carriers of chronic hepatitis B. The use of FibroTest (FT) and ActiTest (AT), biomarkers of fibrosis and necroinflammatory activity, has been previously validated as alternatives to biopsy. We compared the 4-year prognostic value of combining FT-AT and viral load for a better definition of the inactive carrier status.

Methods and Findings

1,300 consecutive CHB patients who had been prospectively followed since 2001 were pre-included. The main endpoint was the absence of liver-related complications, transplantation or death. We used the manufacturers'' definitions of normal FT (< = 0.27), normal AT (< = 0.29) and 3 standard classes for viral load. The adjustment factors were age, sex, HBeAg, ethnic origin, alcohol consumption, HIV-Delta-HCV co-infections and treatment.

Results

1,074 patients with baseline FT-AT and viral load were included: 41 years old, 47% African, 27% Asian, 26% Caucasian. At 4 years follow-up, 50 complications occurred (survival without complications 93.4%), 36 deaths occurred (survival 95.0%), including 27 related to HBV (survival 96.1%). The prognostic value of FT was higher than those of viral load or ALT when compared using area under the ROC curves [0.89 (95%CI 0.84–0.93) vs 0.64 (0.55–0.71) vs 0.53 (0.46–0.60) all P<0.001], survival curves and multivariate Cox model [regression coefficient 5.2 (3.5–6.9; P<0.001) vs 0.53 (0.15–0.92; P = 0.007) vs −0.001 (−0.003−0.000;P = 0.052)] respectively. A new definition of inactive carriers was proposed with an algorithm combining “zero” scores for FT-AT (F0 and A0) and viral load classes. This new algorithm provides a 100% negative predictive value for the prediction of liver related complications or death. Among the 275 patients with the classic definition of inactive carrier, 62 (23%) had fibrosis presumed with FT, and 3 died or had complications at 4 year.

Conclusion

In patients with chronic hepatitis B, a combination of FibroTest-ActiTest and viral load testing accurately defined the prognosis and the inactive carrier status.     

Actin in striated muscle: recent insights into assembly and maintenance

Striated muscle cells are characterised by a para-crystalline arrangement of their contractile proteins actin and myosin in sarcomeres, the basic unit of the myofibrils. A multitude of proteins is required to build and maintain the structure of this regular arrangement as well as to ensure regulation of contraction and to respond to alterations in demand. This review focuses on the actin filaments (also called thin filaments) of the sarcomere and will discuss how they are assembled during myofibrillogenesis and in hypertrophy and how their integrity is maintained in the working myocardium.     

Solar irradiance as the proximate cue for flowering in a tropical moist forest

We compared flowering times predicted by six possible proximate cues involving seasonal changes in rainfall and irradiance and flowering times observed over 30 years of weekly censuses for 19 tree and liana species from Barro Colorado Island (BCI), Panama. Hypotheses concerning variation in the timing and intensity of rainfall failed to predict flowering times in any species. In contrast, 10 to 12 weeks of consistent high levels of irradiance predicted flowering times well for eight species, and six or seven weeks of rapidly increasing levels of irradiance predicted flowering times well for two species. None of the six possible proximate cues predicted flowering times adequately for the nine remaining species. We conclude that high and increasing levels of irradiance are the proximate cues for flowering in many BCI species. The seasonal movements of the Intertropical Convergence Zone cause strong seasonal changes in cloud cover, atmospheric transmissivity, and irradiance reaching the BCI forest. Inter‐annual variation in the timing of movements of the Intertropical Convergence Zone is the most likely cause of inter‐annual variation in the timing of flowering in these species. Much work remains to be done as the physiological mechanisms linking flowering and irradiance are unknown and the proximate cues for flowering remain to be identified for many other BCI species.     

Circadian rhythms in biologically closed electrical circuits of plants

The circadian clock regulates a wide range of electrophysiological and developmental processes in plants. Here, we discuss the direct influence of a circadian clock on biologically closed electrochemical circuits in vivo. The biologically closed electrochemical circuits in the leaves of C. miniata (Kaffir lily), Aloe vera and Mimosa pudica, which regulate their physiology, were analyzed using the charge stimulation method. Plants are able to memorize daytime and nighttime. Even at continuous light or darkness, plants recognize nighttime or daytime and change the input resistance. The circadian clock can be maintained endogenously and has electrochemical oscillators, which can activate ion channels in biologically closed electrochemical circuits. The activation of voltage gated channels depends on the applied voltage, electrical charge, and the speed of transmission of electrical energy from the electrostimulator to plants.     

Cellularity and structure of fresh human coronary thrombectomy specimens; presence of cells with markers of progenitor cells

Acute coronary syndromes and acute myocardial infarctions are often related to plaque rupture and the formation of thrombi at the site of the rupture. We examined fresh coronary thrombectomy specimens from patients with acute coronary syndromes and assessed their structure and cellularity. The thrombectomy specimens consisted of platelets, erythrocytes and inflammatory cells. Several specimens contained multiple cholesterol crystals. Culture of thrombectomy specimens yielded cells growing in various patterns depending on the culture medium used. Culture in serum‐free stem cell enrichment medium yielded cells with features of endothelial progenitor cells which survived in culture for a year. Immunohistochemical analysis of the thrombi revealed cells positive for CD34, cells positive for CD15 and cells positive for desmin in situ, whereas cultured cell from thrombi was desmin positive but pancytokeratin negative. Cells cultured in endothelial cell medium were von Willebrand factor positive. The content of coronary thrombectomy specimens is heterogeneous and consists of blood cells but also possibly cells from the vascular wall and cholesterol crystals. The culture of cells contained in the specimens yielded multiplying cells, some of which demonstrated features of haematopoietic progenitor cells and which differentiated into various cell‐types.     

Isolation and characterization of 23 polymorphic microsatellite loci for a West Indian iguana (Cyclura pinguis) from the British Virgin Islands

Twenty-three polymorphic microsatellite markers were identified and characterized for Cyclura pinguis, a critically endangered species of lizard (Sauria: Iguanidae) native to Anegada Island in the British Virgin Islands. We examined variation at these loci for 39 C. pinguis, finding up to five alleles per locus and an average expected heterozygosity of 0.55. Allele frequency estimates for these microsatellite loci will be used to characterize genetic diversity of captive and wild C. pinguis populations and to estimate relatedness among adult iguanas at the San Diego Zoo that form the nucleus of a captive breeding programme for this critically endangered species.     

Determinants of growing season soil CO2flux in a Minnesota grassland

Soil CO₂ flux was measured across 947 plots at 7 experimentalgrassland sites at the Cedar Creek Natural History Area in order to determinethe relationships between soil CO₂ flux and environmental factors,living plant biomass, and soil C and N. Soil CO₂ flux increased asthe day progressed, and was positively related to aboveground biomass,belowground biomass, and soil % C. However, most of the variation in soilCO₂ flux explained by a multiple regression model(r ² = 0.55) was attributed to the different experimental sites (61%).Soil CO₂ flux increased with increasing aboveground plant biomass(explaining 16% of the model variation),belowground plant biomass (12%), and soil C and C:N ratio(6%). The length of time between aboveground biomass in aplot was clipped and soil CO₂ flux variedamong plots. Soil CO₂ flux declined with increased timesince clipping, supporting the idea that recently fixedcarbon is a significant component of soil CO₂ flux.Soil CO₂ flux did not follow standard Q₁₀relationships. Over a 20 °C temperature range,soil CO₂ flux tended to be lower in warmer plots.More work is necessary to understand what factors explainthe large differences that were seen among experimentalsites in soil CO₂ flux that could not be explainedby biomass or soil properties.     

Transcript-based redefinition of grouped oligonucleotide probe sets using AceView: High-resolution annotation for microarrays

Background  

Extracting biological information from high-density Affymetrix arrays is a multi-step process that begins with the accurate annotation of microarray probes. Shortfalls in the original Affymetrix probe annotation have been described; however, few studies have provided rigorous solutions for routine data analysis.