ALBERT

Description: Sandcracks, which are ubiquitous in Holocene eolian and beach backshore carbonate grainstone on Alligator Point, Cat Island, Bahamas, resemble polygonal mudcracks, but formed in ooid sand without muddy matrix. In experiments on Cat Island beach sand, sediment surfaces cracked polygonally in the absence of mud or biofilms while drying at room temperature due to contraction generated by capillary effects related to surface tension attraction of interstitial water. Gravitational collapse of irregular open pores and repacking of sand grains due to loss of cohesion between particles caused by evaporation of water enhance the cracking process and appearance of polygons by providing space for cracks to expand. The polygons are held together by any remaining capillary moisture and associated meniscus cement, which precipitates as the sand dries. Polygonal sandcracks can be preserved by rapid lithification of carbonate sand, but have been documented only rarely from other localities because their formation requires well-sorted, well-rounded spherical grains rather than those making up the more common, heterogeneous skeletal and peloidal sediment in carbonate settings. Interpretation of this primary sedimentary desiccation structure provides new insights into sedimentation and diagenesis of ooid-rich deposits and can aid in recognizing ancient subaerial exposure horizons.

Description: Laminated carbonates of the Rasthof Formation, deposited in the aftermath of the early Cryogenian low-latitude glaciation (Sturtian, 717–662 Ma), preserve abundant round tests of agglutinated microscopic eukaryotes. Previously, fossil tests were reported in two localities (Ongongo and Okaaru) from microbially laminated carbonates in the Rasthof Formation, which revealed a previous unexplored Cryogenian taphonomic window. In order to better understand the lateral variability in these microfossil assemblages, this work systematically examines fossil tests from two additional localities, South Ombepera and Ombepera, and compares their preservation in thinly and thickly laminated microbial laminites. Cap carbonates in South Ombepera and Ombepera contain abundant, hollow, spheroidal agglutinated tests (50 to 225 µm in diameter). Some of these tests exhibit slitlike or triangular apertures. In contrast, much larger, oval tests with a tapering end dominate the assemblages at Okaaru, whereas oval, laterally compressed and round structures with slits, visors, or central apertures are found at Ongongo. The thinly laminated microbial laminites from Ombepera, South Ombepera, and Okaaru also preserve rare agglutinated tubes attributed to fossils of early Foraminifera. At all four localities, the thinly laminated microbial laminites preserve more microfossils than thickly laminated microbial laminites although these two facies commonly interfinger and are interbedded. This difference shows that conditions present during formation of the thinly laminated microbial laminites favored the preservation of round agglutinators, perhaps during early burial, lithification, and fossilization of the test walls.

Description: Single-nucleotide substitutions and small in-frame insertions or deletions identified in human breast cancer susceptibility genes BRCA1 and BRCA2 are frequently classified as variants of unknown clinical significance (VUS) due to the availability of very limited information about their functional consequences. Such variants can most reliably be classified as pathogenic or non-pathogenic based on the data of their co-segregation with breast cancer in affected families and/or their co-occurrence with a pathogenic mutation. Biological assays that examine the effect of variants on protein function can provide important information that can be used in conjunction with available familial data to determine the pathogenicity of VUS. In this report, we have used a previously described mouse embryonic stem (mES) cell-based functional assay to characterize eight BRCA2 VUS that affect highly conserved amino acid residues and map to the N-terminal PALB2-binding or the C-terminal DNA-binding domains. For several of these variants, very limited co-segregation information is available, making it difficult to determine their pathogenicity. Based on their ability to rescue the lethality of Brca2- deficient mES cells and their effect on sensitivity to DNA-damaging agents, homologous recombination and genomic integrity, we have classified these variants as pathogenic or non-pathogenic. In addition, we have used homology-based modeling as a predictive tool to assess the effect of some of these variants on the structural integrity of the C-terminal DNA-binding domain and also generated a knock-in mouse model to analyze the physiological significance of a residue reported to be essential for the interaction of BRCA2 with meiosis-specific recombinase, DMC1.

Description: Foraminifera are an ecologically important group of modern heterotrophic amoeboid eukaryotes whose naked and testate ancestors are thought to have evolved ~1 Ga ago. However, the single-chambered agglutinated tests of these protists appear in the fossil record only after ca. 580 Ma, coinciding with the appearance of macroscopic and mineralized animals. Here we report the discovery of small, slender tubular microfossils in the Sturtian (ca. 716–635 Ma) cap carbonate of the Rasthof Formation in Namibia. The tubes are 200–1300 µm long and 20–70 µm wide, and preserve apertures and variably wide lumens, folds, constrictions, and ridges. Their sometimes flexible walls are composed of carbonaceous material and detrital minerals. This combination of morphologic and compositional characters is also present in some species of modern single-chambered agglutinated tubular foraminiferans, and is not found in other agglutinated eukaryotes. The preservation of possible early Foraminifera in the carbonate rocks deposited in the immediate aftermath of Sturtian low-latitude glaciation indicates that various morphologically modern protists thrived in microbially dominated ecosystems, and contributed to the cycling of carbon in Neoproterozoic oceans much before the rise of complex animals.

Description: A bstract Here we describe large, complex trace fossils in the late Ediacaran Omkyk Member of the Zaris Formation, Nama Group, southern Namibia. The horizontal trace fossils are preserved on a number of talus blocks from a bedding plane of a cm-thick sandstone lens from a single stratigraphic horizon less than 100 m below an ash bed dated at 547.3 ± 0.7 Ma. The forms consist of overlapping U-shaped spreiten elements with parallel limbs surrounded by an outer tube. Individual U-shaped elements are 0.2 to 1 cm in diameter, the outer tube is less than 3 mm in diameter, and the forms as a whole range from 5 to 30 cm long and 3 to 10 cm wide. The specimens commonly show a change in direction and change in diameter. The morphology of these trace fossils is comparable to backfill structures, particularly specimens of Paleozoic Zoophycos from shallow water environments. Here we interpret these horizontal spreiten-burrows to record the grazing of the trace-maker on or below a textured organic surface. The identification of large late Ediacaran trace fossils is consistent with recent reports of backfilled horizontal burrows below the Precambrian–Cambrian boundary and is suggestive of the appearance of complex feeding habits prior to the Cambrian trace fossil explosion.

Description: Nature Geoscience 7, 736 (2014). doi:10.1038/ngeo2229 Authors: G. Mariotti, S. B. Pruss, J. T. Perron & T. Bosak Wrinkle structures on sandy bed surfaces were present in some of the earliest sedimentary environments, but are rare in modern environments. These enigmatic millimetre- to centimetre-scale ridges or pits are particularly common in sediments that harbour trace fossils and imprints of early animals, and appeared in the aftermath of some large mass extinctions. Wrinkle structures have been interpreted as possible remnants of microbial mats, but the formation mechanism and associated palaeoenvironmental and palaeoecological implications of these structures remain debated. Here we show that microbial aggregates can form wrinkle structures on a bed of bare sand in wave tank experiments. Waves with a small orbital amplitude at the bed surface do not move sand grains directly. However, they move millimetre-size, light microbial fragments and thereby produce linear sand ridges and rounded scour pits at the wavelengths observed in nature within hours. We conclude that wrinkle structures are morphological biosignatures that form at the sediment–water interface in wave-dominated environments, and not beneath microbial mats as previously thought. During early animal evolution, grazing by eukaryotic organisms may have temporarily increased the abundance of microbial fragments and thus the production of wrinkle structures.

Description: Neoproterozoic strata in Death Valley, California, contain eukaryotic microfossils and glacial deposits that have been used to assess the severity of putative snowball Earth events and the biological response to extreme environmental change. These successions also contain evidence for synsedimentary faulting that has been related to the rifting of Rodinia, and in turn the tectonic context of the onset of snowball Earth. These interpretations hinge on local geological relationships and both regional and global stratigraphic correlations. Here, we present new geological mapping, measured stratigraphic sections, carbon and strontium isotope chemostratigraphy, and micropaleontology from the Neoproterozoic glacial deposits and bounding strata in Death Valley. These new data enable us to refine regional correlations, both across Death Valley and throughout Laurentia, and construct a new age model for glacigenic strata and microfossil assemblages. Particularly, our remapping of the Kingston Peak Formation in the Saddle Peak Hills and near the type locality shows for the first time that glacial deposits of both the Marinoan and Sturtian glaciations can be distinguished in southeastern Death Valley, and that beds containing vase-shaped microfossils are slump blocks derived from the underlying strata. These slump blocks are associated with multiple overlapping unconformities that developed during synsedimentary faulting, which is a common feature of Cyrogenian strata along the margin of Laurentia from California to Alaska. With these data, we conclude that all of the microfossils that have been described to date in Neoproterozoic strata of Death Valley predate the glaciations and do not bear on the severity, extent, or duration of Neoproterozoic snowball Earth events.

Description: Abstract 22 Introduction: Type 1 von Willebrand disease (VWD) is caused by mutations that result in moderate decreases in VWF antigen (VWF:Ag is 5–50% of normal levels) and a mild bleeding phenotype. The common recurrent VWF missense mutation Y1584C is associated with mildly decreased VWF:Ag levels, increased ADAMTS13 cleavage, as well as a possible increase in clearance. The Vicenza mutation, R1205H, exhibits a more severe phenotype (VWF:Ag ∼10%) and accelerated clearance. Although well described in patients and through in vitro studies, extensive controlled in vivo investigation of these mutations has yet to be performed. In this study, we compared both Y1584C and R1205H to wild type VWF using hydrodynamic gene delivery of mouse VWF and ADAMTS13 transgenes in the VWF knockout mouse to determine the pathological mechanisms associated with these variants. Methods: Hydrodynamic injections were performed using 100 μ g wild type (WT) or mutant mouse Vwf cDNA in Ringer's solution in 7–9 week old C57Bl6 VWF knockout mice, replacing plasma VWF. Co-injections with mouse Adamts13 cDNA were also performed. Mice were sampled at days 2, 5, 8, and then weekly. Mouse plasma was analyzed for complete blood counts, VWF:Ag, VWF propeptide, and VWF multimer structure. Thrombotic injury was induced using ferric chloride injury to the arterioles of the cremaster in VWF knockout mice expressing VWF:Ag levels from 0.5–2 U/ml. Platelets were labeled with Rhodamine-6G to evaluate platelet accumulation. Time to stable vessel occlusion and platelet accumulation by relative fluorescence intensity were compared. Results: Hydrodynamic injection caused no adverse events in any animals. Complete blood count values were unaffected for both variants compared to WT. Initial high VWF:Ag values at day 2 were similar for WT VWF (25.4 ± 2.5 U/ml, n= 12, mean U/ml±SEM, n) and Y1584C (26.8 ± 5.5, n= 10), but R1205H levels were 36% lower (16.3 ± 2.1, n= 10). Lower VWF:Ag levels were demonstrated in both “homozygous” and “heterozygous” forms for both type 1 mutations from days 14–42, when VWF expression plateaus. R1205H VWF:Ag was 34.3 ± 5.9% of WT (P 〈 0.001) and “heterozygous” 1:1 ratio R1205H/WT co-delivery was 27.5 ± 4.7% (p 〈 0.001). Y1584C was 29.4 ± 7.5% of WT (P 〈 0.001), and Y1584C/WT was 51.1 ± 4.6% (p 〈 0.001). VWF propeptide to VWF:Ag ratios (days 2–42) demonstrate that R1205H mouse VWF had an increased clearance rate (165.4 ± 13.5%, p 〈 0.001), while Y1584C was normal (97.1 ± 6.8 %, P 〉 0.05) compared to WT (100.0 ± 10.0%). The R1205H mutation showed no significant difference in multimer structure by mean multimer band numbers (days 2 to 42, 93 ± 16%, n = 4, P 〉 0.05) to wild type VWF (100 ± 12%, n = 4). In contrast, Y1584C had a significant decrease (66 ± 18%, n = 4, P 〈 0.001). This effect was exaggerated by co-delivery of mouse ADAMTS13 for Y1584C, but not R1205H. Y1584C showed reduced thrombus formation in a ferric chloride injury model while R1205H demonstrated similar thrombogenic activity to wild type VWF. Mean occlusion times were WT = 29.9 ± 2.1 minutes, n = 8, R1205H = 29.1 ± 4.0, n = 8 (p 〉 0.05), and Y1584C = 38.7 ± 1.1, n = 9 (p = 0.001). Total platelet accumulation was decreased for Y1584C (83.6 ± 6.3%, p = 0.043), but was similar for R1205H (103 ± 6.3, P = 0.72) and WT (100 ± 5.3%). Conclusions: This study demonstrates that these two type 1 VWD mutations have a strong observable effect in the VWF knockout mouse model. R1205H exhibits a large decrease in VWF:Ag levels and evidence of accelerated clearance with R1205H. However, there is no alteration in multimer structure and apparently normal participation in a thrombosis model. Y1584C, in contrast, shows a loss of high molecular weight multimers that is exacerbated by the additional expression of ADAMTS13, indicating that ADAMTS13 cleavage is increased. Y1584C also has an initially high VWF:Ag level that was less than WT levels from day 14 onward, but shows no alteration in clearance, suggesting that there is a biosynthetic defect. Y1584C shows a significant defect in the arteriolar thrombosis model, presenting a Type 2A VWD-like phenotype in the mouse model, which is more severe than the human phenotype. This study has elucidated several novel mechanistic details for these two mutations and highlights that the pathogenic aspects of type 1 VWD can be recapitulated in the VWF knockout hydrodynamic injection model. Disclosures: No relevant conflicts of interest to declare.

Description: Type 1 VWD is the mild to moderate reduction of VWF levels. This study examined the mechanisms underlying 2 common type 1 VWD mutations, the severe R1205H and more moderate Y1584C. In vitro biosynthesis was reduced for both mutations in human and mouse VWF, with the effect being more severe in R1205H. VWF knockout mice received hydrodynamic injections of mouse Vwf cDNA. Lower VWF antigen levels were demonstrated in both homozygous and heterozygous forms for both type 1 mutations from days 14-42. Recombinant protein infusions and hydrodynamic-expressed VWF propeptide to antigen ratios demonstrate that R1205H mouse VWF has an increased clearance rate, while Y1584C is normal. Recombinant ADAMTS13 digestions of Y1584C demonstrated enhanced cleavage of both human and mouse VWF115 substrates. Hydrodynamic-expressed VWF shows a loss of high molecular weight multimers for Y1584C compared with wild-type and R1205H. At normal physiologic levels of VWF, Y1584C showed reduced thrombus formation in a ferric chloride injury model while R1205H demonstrated similar thrombogenic activity to wild-type VWF. This study has elucidated several novel mechanisms for these mutations and highlights that the type 1 VWD phenotype can be recapitulated in the VWF knockout hydrodynamic injection model.