A Probable Neoceratopsian Manus Track from the Nanushuk Formation (Albian, Northern Alaska)

We report a likely neoceratopsian manus track from an exposure of the Nanushuk Formation along the Colville River in northern Alaska. The track described here containts the impressions of five digits, arranged as an arc, which identify this specimen as a manus. Details of the impression suggest that it is neoceratopsian rather than ankylosaurian. The length of the chord of the arc of the track is approximately 25 cm, which is half the size of manus tracks found west of Denver, Colorado, USA attributed to the 10 m long Maastrichtian Triceratops. The Nanushuk Formation is a succession of complexly intertonguing marine and nonmarine strata interpreted as shelf, deltaic, strandplain, fluvial, and alluvial overbank deposits. Deposited in the foreland basin north f the Brooks Range, the rock unit is present throughout most of the northern foothills belt and subsurface of the central and western North Slope coastal plain. Fossil and radiometric data place outcrop within the Albian. If the identification of the track is correct, this is one of the earlies occurrences of neoceratopsians from North America. The occurrence of this track in Alaska substantiates the biogeographic model of faunal exchange between Asia and North America through a Cretaceous land bridge known as Beringia.Presentamos una probable huella de mano atribuida a neoceratopsido de un afloramiento de la Formación Nanushuk a lo largo del río Colville, en el norte de Alaska. La huella descrita contiene la impresión de cinco dígitos, dispuestos en arco, que identifican este especimen como una mano. Los detalles de la impresion sugieren que se trata de un neoceratopsido mas que de un ankilosaurio. La longitud de la cuerda del arco de la huella es aproximadamente de 25 cm, lo cual es la mitad del tamano de las huellas de mano encontradas al oeste de Denver, Colorado, EE.UU, y atribuidas a Triceratops, un taxon de unos 10 m de largo de edad Maastrichtiense. La Formacion Nanushuk es una sucesion de capas de origen marino y no marino complejamente interdigitadas e interpretadas como depósitos de plataforma, deltaicos de playas progradantes, fluviales y de overbank aluvial. Depositada en una cuenca de antepais al norte del Brooks Range, la unidad de roca esta presente a lo largo de la mayor parte de la franja septentrional de colinas, y en el subsuelo de la zona central y occidental, de la llanura costera de North Slope. Los fosiles y los datos radiometricos situan este afloramiento en el Albiense. Si la identificación de la huella es correcta, es una de las apariciones más tempranas de neoceratopsidos en Norteamaerica. La aparición de esta huella en Alaska apoya el modelo biogeográfico de intercambio faunístico entre Asia y Norteamerica a traves de un puente de tierra cretacico conocido como Beringia

Identification of novel loci associated with hip shape:a meta-analysis of genome-wide association studies

This study was funded by Arthritis Research UK project grant 20244, which also provided salary funding for DB and CVG. LP works in the MRC Integrative Epidemiology Unit, a UK MRC‐funded unit (MC_ UU_ 12013/4 & MC_UU_12013/5). ALSPAC: We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. ALSPAC data collection was supported by the Wellcome Trust (grants WT092830M; WT088806; WT102215/2/13/2), UK Medical Research Council (G1001357), and University of Bristol. The UK Medical Research Council and the Wellcome Trust (102215/2/13/2) and the University of Bristol provide core support for ALSPAC. Framingham Heart Study: The Framingham Osteoporosis Study is supported by grants from the National Institute of Arthritis, Musculoskeletal, and Skin Diseases and the National Institute on Aging (R01 AR41398, R01 AR 061162, R01 AR050066, and R01 AR061445). The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource project. The Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine were supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01‐HC‐25195) and its contract with Affymetrix, Inc., for genotyping services (N02‐HL‐6‐4278). Analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA‐II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. DK was also supported by Israel Science Foundation grant #1283/14. TDC and DR thank Dr Claire Reardon and the entire Harvard University Bauer Core facility for assistance with ATAC‐seq next generation sequencing. This work was funded in part by the Harvard University Milton Fund, NSF (BCS‐1518596), and NIH NIAMS (1R01AR070139‐01A1) to TDC. MrOS: The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) provides funding for the MrOS ancillary study “Replication of candidate gene associations and bone strength phenotype in MrOS” under the grant number R01 AR051124. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) provides funding for the MrOS ancillary study “GWAS in MrOS and SOF” under the grant number RC2 AR058973. SOF: The Study of Osteoporotic Fractures (SOF) is supported by National Institutes of Health funding. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576. TwinsUK: The study was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007‐2013). The study also receives support from the National Institute for Health Research (NIHR)‐funded BioResource, Clinical Research Facility, and Biomedical Research Centre based at Guy's and St Thomas’ NHS Foundation Trust in partnership with King's College London. SNP genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. This study was also supported by the Australian National Health and Medical Research Council (project grants 1048216 and 1127156), the Sir Charles Gairdner Hospital RAC (SGW), and the iVEC/Pawsey Supercomputing Centre (project grants Pawsey0162 and Director2025 [SGW]). The salary of BHM was supported by a Raine Medical Research Foundation Priming Grant. The Umeå Fracture and Osteoporosis Study (UFO) is supported by the Swedish Research Council (K20006‐72X‐20155013), the Swedish Sports Research Council (87/06), the Swedish Society of Medicine, the Kempe‐Foundation (JCK‐1021), and by grants from the Medical Faculty of Umeå Unviersity (ALFVLL:968:22‐2005, ALFVL:‐937‐2006, ALFVLL:223:11‐2007, and ALFVLL:78151‐2009) and from the county council of Västerbotten (Spjutspetsanslag VLL:159:33‐2007). This publication is the work of the authors and does not necessarily reflect the views of any funders. None of the funders had any influence on data collection, analysis, interpretation of the results, or writing of the paper. DB will serve as the guarantor of the paper. Authors’ roles: Study conception and design: DAB, JSG, RMA, LP, DK, and JHT. Data collection: DJ, DPK, ESO, SRC, NEL, BHM, FMKW, JBR, SGW, TDC, BGF, DAL, CO, and UP‐L. Data analysis: DAB, DSE, FKK, JSG, FRS, CVG, RJB, RMA, SGW, EG, TDC, DR, and TB. Data interpretation: JSG, RMA, TDC, DR, DME, LP, DK, and JHT. Drafting manuscript: DAB and JHT. Revising manuscript content: JHT. All authors approved the final version of manuscript. DAB takes responsibility for the integrity of the data analysis.Peer reviewedPublisher PD

The Endoplasmic Reticulum Chaperone Protein GRP94 Is Required for Maintaining Hematopoietic Stem Cell Interactions with the Adult Bone Marrow Niche

Hematopoietic stem cell (HSC) homeostasis in the adult bone marrow (BM) is regulated by both intrinsic gene expression products and interactions with extrinsic factors in the HSC niche. GRP94, an endoplasmic reticulum chaperone, has been reported to be essential for the expression of specific integrins and to selectively regulate early T and B lymphopoiesis. In GRP94 deficient BM chimeras, multipotent hematopoietic progenitors persisted and even increased, however, the mechanism is not well understood. Here we employed a conditional knockout (KO) strategy to acutely eliminate GRP94 in the hematopoietic system. We observed an increase in HSCs and granulocyte-monocyte progenitors in the Grp94 KO BM, correlating with an increased number of colony forming units. Cell cycle analysis revealed that a loss of quiescence and an increase in proliferation led to an increase in Grp94 KO HSCs. This expansion of the HSC pool can be attributed to the impaired interaction of HSCs with the niche, evidenced by enhanced HSC mobilization and severely compromised homing and lodging ability of primitive hematopoietic cells. Transplanting wild-type (WT) hematopoietic cells into a GRP94 null microenvironment yielded a normal hematology profile and comparable numbers of HSCs as compared to WT control, suggesting that GRP94 in HSCs, but not niche cells, is required for maintaining HSC homeostasis. Investigating this, we further determined that there was a near complete loss of integrin α4 expression on the cell surface of Grp94 KO HSCs, which showed impaired binding with fibronectin, an extracellular matrix molecule known to play a role in mediating HSC-niche interactions. Furthermore, the Grp94 KO mice displayed altered myeloid and lymphoid differentiation. Collectively, our studies establish GRP94 as a novel cell intrinsic factor required to maintain the interaction of HSCs with their niche, and thus regulate their physiology

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

The National Kidney Foundation of Illinois KidneyMobile: a mobile resource for community based screenings of chronic kidney disease and its risk factors

Abstract Background Early detection and treatment of chronic kidney disease (CKD) and its risk factors improves outcomes; however, many high-risk individuals lack access to healthcare. The National Kidney Foundation of Illinois (NKFI) developed the KidneyMobile (KM) to conduct community-based screenings, provide disease education, and facilitate follow-up appointments for diabetes, hypertension, and CKD. Methods Cross-sectional design. Adults > = 18 years of age participated in NKFI KM screenings across Illinois between 2005 and 2011. Sociodemographic and medical history were self-reported using structured interviews; laboratory data and blood pressure were assessed using standard procedures. Results Among 20,770 participants, mean age was 53.5 years, 68% were female, 49% were African-American or Hispanic, 21% primarily spoke Spanish, and at least 27% lacked health insurance. Seventy-eight percent of participants with elevated blood pressure (≥ 140/90 mmHg) were aware of having hypertension, 93% of participants with abnormal blood glucose (fasting glucose > 126 mg/dl or a random glucose of > 200 mg/dL) were aware of having diabetes, and 19% of participants with albuminuria (> 30 mg/gm) were aware of having CKD. In participants reporting hypertension, 47% had blood pressure ≥ 140/90 mmHg, and in those reporting diabetes, 56% had blood glucose ≥ 130 mg/dl (fasting) or ≥ 180 mg/dl (random). Among 4937 participants with abnormal screening findings that participated in follow-up interviews, 69% reported having further medical evaluation. Conclusions A high-risk disadvantaged population is being reached by the NKFI KidneyMobile and connected with healthcare services. A significant proportion of participants were newly informed of having abnormal results suggestive of diabetes, hypertension, and/or CKD or that their diabetes and hypertension were inadequately controlled

Directional fractal signature methods for trabecular bone texture in hand radiographs: Data from the Osteoarthritis Initiative

Purpose: To develop directional fractal signature methods for the analysis of trabecular bone (TB) texture in hand radiographs. Problems associated with the small size of hand bones and the orientation of fingers were addressed. Methods: An augmented variance orientation transform (AVOT) and a quadrant rotating grid (QRG) methods were developed. The methods calculate fractal signatures (FSs) in different directions. Unlike other methods they have the search region adjusted according to the size of bone region of interest (ROI) to be analyzed and they produce FSs defined with respect to any chosen reference direction, i.e., they work for arbitrary orientation of fingers. Five parameters at scales ranging from 2 to 14 pixels (depending on image size and method) were derived from rose plots of Hurst coefficients, i.e., FS in dominating roughness (FSSta), vertical (FSV) and horizontal (FSH) directions, aspect ratio (StrS), and direction signatures (StdS), respectively. The accuracy in measuring surface roughness and isotropy/anisotropy was evaluated using 3600 isotropic and 800 anisotropic fractal surface images of sizes between 20 × 20 and 64 × 64 pixels. The isotropic surfaces had FDs ranging from 2.1 to 2.9 in steps of 0.1, and the anisotropic surfaces had two dominating directions of 30° and 120°. The methods were used to find differences in hand TB textures between 20 matched pairs of subjects with (cases: approximate Kellgren-Lawrence (KL) grade ≥2) and without (controls: approximate KL grade <2) radiographic hand osteoarthritis (OA). The OA Initiative public database was used and 20 × 20 pixel bone ROIs were selected on 5th distal and middle phalanges.The performance of the AVOT and QRG methods was compared against a variance orientation transform (VOT) method developed earlier [M. Wolski, P. Podsiadlo, and G. W. Stachowiak, “Directional fractal signature analysis of trabecular bone: evaluation of different methods to detect early osteoarthritis in knee radiographs,” Proc. Inst. Mech. Eng., Part H223, 211–236 (2009)]. Results: The AVOT method correctly quantified the isotropic and anisotropic surfaces for all image sizes and scales. Values of FSSta were significantly different (P < 0.05) between the isotropic surfaces. Using the VOT and QRG methods no differences were found at large scales for the isotropic surfaces that are smaller than 64 × 64 and 48 × 48 pixels, respectively, and at some scales for the anisotropic surfaces with size 48 × 48 pixels. Compared to controls, using the AVOT and QRG methods the authors found that OA TB textures were less rough (P < 0.05) in the dominating and horizontal directions (i.e., lower FSSta and FSH), rougher in the vertical direction (i.e., higher FSV) and less anisotropic (i.e., higher StrS) than controls. No differences were found using the VOT method. Conclusions: The AVOT method is well suited for the analysis of bone texture in hand radiographs and it could be potentially useful for early detection and prediction of hand OA