Morphology and Development of Ice Patches in Northwest Territories, Canada

Permanent ice patches in the western Canadian Subarctic have been recently identified as sources of cryogenically preserved artifacts and biological specimens. The formation, composition, and constancy of these ice patches have yet to be studied. As part of the Northwest Territories (NWT) Ice Patch Study, ground-penetrating radar (GPR) and ice coring were used to examine the stratigraphy and internal structure of two ice patches. Results show the patches are composed of a core of distinct offset units, up to several metres thick, covered by a blanket of firn and snow. The interfaces between the units of ice are often demarcated by thin sections of frozen caribou dung and fine sediment. Radiocarbon dates of dung extracted from ice cores have revealed a long history for these perennial patches, up to 4400 years BP. Ice patch growth is discontinuous and occurs intermittently. Extensive time gaps exist between the units of ice, indicating that summers of catastrophic melt can interrupt extended periods of net accumulation. The results of this work not only display the character of ice patch development, but also indicate the significant role that ice patches can play in reconstructing the paleoenvironmental conditions of an area.Récemment, on a déterminé que les névés permanents du subarctique de l’Ouest canadien constituent des sources d’artefacts et de spécimens biologiques préservés cryogéniquement. La formation, la composition et la constance de ces névés n’ont toujours pas été étudiées. Dans le cadre de l’étude des névés des Territoires du Nord-Ouest, on a recouru à des géoradars (GPR) et au carottage de la glace pour examiner la stratigraphie et la structure interne de deux névés. Les résultats indiquent que les névés sont composés d’un noyau d’unités distinctes et décalées, mesurant plusieurs mètres d’épaisseur et recouvertes d’une couverture de vieille neige et de neige. L’interface entre les unités de glace est souvent démarquée par de minces sections de déjections de caribou gelées et de sédiments fins. La datation au radiocarbone des déjections extraites des carottes de glace révèle que ces névés pérennes ont une longue histoire, remontant jusqu’à 4400 ans BP. L’amplification des névés est discontinue et se produit de manière intermittente. Des écarts de temps considérables existent entre les unités de glace, ce qui laisse entendre que des étés de fonte catastrophique peuvent interrompre les périodes prolongées d’accumulation nette. Les résultats de cette étude laissent non seulement entrevoir le caractère de la formation des névés, mais indiquent également le rôle important que les névés peuvent jouer dans la reconstruction des conditions paléoenvironnementales d’une région

Diet and Habitat of Mountain Woodland Caribou Inferred from Dung Preserved in 5000-year-old Alpine Ice in the Selwyn Mountains, Northwest Territories, Canada

Alpine ice patches are unique repositories of cryogenically preserved archaeological artefacts and biological specimens. Recent melting of ice in the Selwyn Mountains, Northwest Territories, Canada, has exposed layers of dung accumulated during seasonal use of ice patches by mountain woodland caribou of the ancestral Redstone population over the past ca. 5250 years. Although attempts to isolate the DNA of known caribou parasites were unsuccessful, the dung has yielded numerous well-preserved and diverse plant remains and palynomorphs. Plant remains preserved in dung suggest that the ancestral Redstone caribou population foraged on a variety of lichens (30%), bryophytes and lycopods (26.7%), shrubs (21.6%), grasses (10.5%), sedges (7.8%), and forbs (3.4%) during summer use of alpine ice. Dung palynomorph assemblages depict a mosaic of plant communities growing in the caribou’s summer habitat, including downslope boreal components and upslope floristically diverse herbaceous communities. Pollen and spore content of dung is only broadly similar to late Holocene assemblages preserved in lake sediments and peat in the study region, and differences are likely due to the influence of local vegetation and animal forage behaviour. The 5000-year legacy of summer use of alpine ice patches by mountain woodland caribou suggests that these small, long-lived features may be important for the health of caribou populations in the Selwyn/Mackenzie Mountain range.Les névés des régions alpines constituent des réserves uniques d’artefacts archéologiques et de spécimens biologiques préservés cryogéniquement. La fonte récente des glaces de la chaîne de Selwyn, dans les Territoires du Nord-Ouest, au Canada, a mis au jour des couches de déjections animales qui ont été accumulées lors de l’usage saisonnier des névés par le caribou des bois des montagnes de la population ancestrale de Redstone au cours des quelques 5 250 dernières années. Bien que les tentatives visant à isoler l’ADN des parasites connus du caribou aient échoué, les déjections ont permis de repérer de nombreux restes et palynomorphes de végétaux bien préservés et variés. Les restes de végétaux qui ont été conservés dans les déjections animales laissent croire que la population de caribou ancestrale de Redstone s’alimentait d’une variété de lichens (30 %), de bryophytes et de lycopodes (26,7 %), d’arbrisseaux (21,6 %), de graminées (10,5 %), de foin plat (7,8 %) et de plantes herbacées non graminoïdes (3,4 %) lorsqu’ils utilisaient la glace alpine pendant l’été. Les assemblages de palynomorphes provenant des déjections laissent entrevoir la croissance d’une mosaïque de peuplements végétaux au sein de l’habitat d’été du caribou, ce qui comprend des composantes boréales en pentes descendantes et des peuplements végétaux herbacés floristiquement variés en pentes ascendantes. La teneur en pollen et en spores des déjections animales est seulement largement similaire aux assemblages de l’Holocène tardif préservés dans les sédiments lacustres et dans la tourbe de la région visée par l’étude. Les différences sont vraisemblablement attribuables à l’influence de la végétation locale et au comportement alimentaire des animaux. L’utilisation estivale des névés des régions alpines par le caribou des bois des montagnes ces 5 000 dernières années laisse entrevoir que ces petites caractéristiques longévives pourraient revêtir de l’importance pour la santé des populations de caribou de la chaîne de Selwyn et des monts Mackenzie

Synthetic oligosaccharides can replace animal-sourced low–molecular weight heparins

Full-sized and low–molecular weight heparins are widely used to treat a variety of clotting disorders. Although low–molecular weight heparins are safer and more convenient to use than full-size heparin, they are still animal-derived products that present a risk of contamination and supply chain interruptions and are limited with respect to standardization and reversibility of anticoagulation. A method developed by Xu et al . offers a potential alternative to animal-sourced heparins in the form of a chemical synthesis process that can be scaled up to produce heparin dodecasaccharides with reversible activity in adequate quantities for potential therapeutic use

Geomorphological mapping with a small unmanned aircraft system (sUAS): feature detection and accuracy assessment of a photogrammetrically-derived digital terrain model

Sherpa Romeo green journal. Permission to archive accepted author manuscript.Small unmanned aircraft systems (sUAS) are a relatively new type of aerial platform for acquiring high-resolution remote sensing measurements of Earth surface processes and landforms. However, despite growing application there has been little quantitative assessment of sUAS performance. Here we present results from a field experiment designed to evaluate the accuracy of a photogrammetrically-derived digital terrain model (DTM) developed from imagery acquired with a low-cost digital camera onboard an sUAS. We also show the utility of the highresolution (0.1 m) sUAS imagery for resolving small-scale biogeomorphic features. The experiment was conducted in an area with active and stabilized aeolian landforms in the southern Canadian Prairies. Images were acquired with a Hawkeye RQ-84Z Aerohawk fixed-wing sUAS. A total of 280 images were acquired along 14 flight lines, covering an area of 1.95 km2. The survey was completed in 4.5 hours, including GPS surveying, sUAS setup and flight time. Standard image processing and photogrammetric techniques were used to produce a 1 m resolution DTM and a 0.1 m resolution orthorectified image mosaic. The latter revealed previously un-mapped bioturbation features. The vertical accuracy of the DTM was evaluated with 99 Real-Time Kinematic GPS points, while 20 of these points were used to quantify horizontal accuracy. The horizontal root mean squared error (RMSE) of the orthoimage was 0.18 m, while the vertical RMSE of the DTM was 0.29 m, which is equivalent to the RMSE of a bare earth LiDAR DTM for the same site. The combined error from both datasets was used to define a threshold of the minimum elevation difference that could be reliably attributed to erosion or deposition in the seven years separating the sUAS and LiDAR datasets. Overall, our results suggest that sUAS-acquired imagery may provide a low-cost, rapid, and flexible alternative to airborne LiDAR for geomorphological mapping.Ye

Human Cytomegalovirus UL29/28 Protein Interacts with Components of the NuRD Complex Which Promote Accumulation of Immediate-Early RNA

Histone deacetylation plays a pivotal role in regulating human cytomegalovirus gene expression. In this report, we have identified candidate HDAC1-interacting proteins in the context of infection by using a method for rapid immunoisolation of an epitope-tagged protein coupled with mass spectrometry. Putative interactors included multiple human cytomegalovirus-coded proteins. In particular, the interaction of pUL38 and pUL29/28 with HDAC1 was confirmed by reciprocal immunoprecipitations. HDAC1 is present in numerous protein complexes, including the HDAC1-containing nucleosome remodeling and deacetylase protein complex, NuRD. pUL38 and pUL29/28 associated with the MTA2 component of NuRD, and shRNA-mediated knockdown of the RBBP4 and CHD4 constituents of NuRD inhibited HCMV immediate-early RNA and viral DNA accumulation; together this argues that multiple components of the NuRD complex are needed for efficient HCMV replication. Consistent with a positive acting role for the NuRD elements during viral replication, the growth of pUL29/28- or pUL38-deficient viruses could not be rescued by treating infected cells with the deacetylase inhibitor, trichostatin A. Transient expression of pUL29/28 enhanced activity of the HCMV major immediate-early promoter in a reporter assay, regardless of pUL38 expression. Importantly, induction of the major immediate-early reporter activity by pUL29/28 required functional NuRD components, consistent with the inhibition of immediate-early RNA accumulation within infected cells after knockdown of RBBP4 and CHD4. We propose that pUL29/28 modifies the NuRD complex to stimulate the accumulation of immediate-early RNAs

GSK2801, a BAZ2/BRD9 bromodomain inhibitor, synergizes with BET inhibitors to induce apoptosis in triple-negative breast cancer

Screening of an inhibitor library targeting kinases and epigenetic regulators identified several molecules having antiproliferative synergy with extraterminal domain (BET) bromodomain (BD) inhibitors (JQ1, OTX015) in triplenegative breast cancer (TNBC). GSK2801, an inhibitor of BAZ2A/B BDs, of the imitation switch chromatin remodeling complexes, and BRD9, of the SWI/SNF complex, demonstrated synergy independent of BRD4 control of P-TEFb- mediated pause-release of RNA polymerase II. GSK2801 or RNAi knockdown of BAZ2A/B with JQ1 selectively displaced BRD2 at promoters/enhancers of ETS-regulated genes. Additional displacement of BRD2 from rDNA in the nucleolus coincided with decreased 45S rRNA, revealing a function of BRD2 in regulating RNA polymerase I transcription. In 2D cultures, enhanced displacement of BRD2 from chromatin by combination drug treatment induced senescence. In spheroid cultures, combination treatment induced cleaved caspase-3 and cleaved PARP characteristic of apoptosis in tumor cells. Thus, GSK2801 blocks BRD2-driven transcription in combination with BET inhibitor and induces apoptosis of TNBC

Molecular characterisation and clinical outcome of B-cell precursor acute lymphoblastic leukaemia with IG-MYC rearrangement

Rarely, immunophenotypically immature B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) carries an immunoglobulin-MYC rearrangement (IG-MYC-r). This can result in diagnostic confusion with Burkitt lymphoma/leukaemia and use of unproven individualised treatment schedules. Here we contrast the molecular characteristics of these conditions and investigate historic clinical outcome data. We identified 90 cases registered on a national BCP-ALL clinical trial/registry. Where present, diagnostic material underwent cytogenetic, exome, methylome and transcriptome analysis. Outcome was analysed to define 3-year event free survival (EFS) and overall survival (OS). IG-MYC-r was identified in diverse cytogenetic backgrounds, co-existing with either: established BCP-ALL specific abnormalities (high hyperdiploidy n=3, KMT2A-rearrangement n=6, iAMP21 n=1, BCR-ABL n=1); BCL2/BCL6-rearrangements (n=15); or, most commonly, as the only defining feature (n=64). Within this final group, precursor-like V(D)J breakpoints predominated (8/9) and KRAS mutations were common (5/11). DNA methylation identified a cluster of V(D)J rearranged cases, clearly distinct from Burkitt leukaemia/lymphoma. Children with IG-MYC-r within that subgroup had 3-year EFS of 47% and OS of 60%, representing a high-risk BCP-ALL. To develop effective management strategies this patient group must be allowed access to contemporary, minimal residual disease adapted, prospective clinical trial protocols