bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophages in Progressive Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections
Authors: DiNapoli Sarah R. , Hirsch Vanessa M. , Brenchley Jason M. 
Published: June 2016

ABSTRACT

The cells that are targeted by primate lentiviruses (HIV and simian immunodeficiency virus [SIV]) are of intense interest given the renewed effort to identify potential cures for HIV. These viruses have been reported to infect multiple cell lineages of hematopoietic origin, including all phenotypic and functional CD4 T cell subsets. The two most commonly reported cell types that become infected
in vivo
are memory CD4 T cells and tissue-resident macrophages. Though viral infection of CD4 T cells is routinely detected in both HIV-infected humans and SIV-infected Asian macaques, significant viral infection of macrophages is only routinely observed in animal models wherein CD4 T cells are almost entirely depleted. Here we review the roles of macrophages in lentiviral disease progression, the evidence that macrophages support viral replication
in vivo
, the animal models where macrophage-mediated replication of SIV is thought to occur, how the virus can interact with macrophages
in vivo
, pathologies thought to be attributed to viral replication within macrophages, how viral replication in macrophages might contribute to the asymptomatic phase of HIV/SIV infection, and whether macrophages represent a long-lived reservoir for the virus.
Recapitulating Cross-Species Transmission of Simian Immunodeficiency Virus SIVcpz to Humans by Using Humanized BLT Mice
Authors: Yuan Zhe , Kang Guobin , Ma Fangrui , Lu Wuxun , Fan Wenjin , Fennessey Christine M. , Keele Brandon F. , Li Qingsheng 
Published: June 2016

ABSTRACT

The origins of human immunodeficiency virus type 1 (HIV-1) have been widely accepted to be the consequences of simian immunodeficiency viruses from wild chimpanzees (SIVcpz) crossing over to humans. However, there has not been any
in vivo
study of SIVcpz infection of humans. Also, it remains largely unknown why only specific SIVcpz strains have achieved cross-species transmission and what transmission risk might exist for those SIVcpz strains that have not been found to infect humans. Closing this knowledge gap is essential for better understanding cross-species transmission and predicting the likelihood of additional cross-species transmissions of SIV into humans. Here we show that humanized bone marrow, thymus, and liver (hu-BLT) mice are susceptible to all studied strains of SIVcpz, including the inferred ancestral viruses of pandemic and nonpandemic HIV-1 groups M (SIVcpzMB897) and N (SIVcpzEK505) as well as strains that have not been found in humans (SIVcpzMT145 and SIVcpzBF1167). Importantly, the ability of SIVcpz to cross the interspecies barrier to infect humanized mice correlates with their phylogenetic distance to pandemic HIV-1. We also identified mutations of SIVcpzMB897 (Env G411R and G413R) and SIVcpzBF1167 (Env H280Q and Q380R) at 14 weeks postinoculation. Together, our results have recapitulated the events of SIVcpz cross-species transmission to humans and identified mutations that occurred during the first 16 weeks of infection, providing
in vivo
experimental evidence that the origins of HIV-1 are the consequence of SIVcpz crossing over to humans. This study also revealed that SIVcpz viruses whose inferred descendants have not been found in humans still have the potential to cause an HIV-1-like zoonosis.

IMPORTANCE
It is believed that the origins of HIV-1 are the consequence of SIV from wild chimpanzees crossing over to humans. However, the origins of HIV-1 have been linked back to only specific SIVcpz strains. There have been no experiments that directly test the
in vivo
cross-species transmissibility of SIVcpz strains to humans. This is the first
in vivo
study of SIVcpz cross-species transmission. With the humanized-BLT mouse model, we have provided
in vivo
experimental evidence of multiple SIVcpz strains crossing over to humans and identified several important mutations of divergent SIVcpz strains after long-term replication in human cells. We also found that the cross-species transmission barrier of SIVcpz to humans correlates with their phylogenetic distance to pandemic HIV-1 group M. Importantly, this work provides evidence that SIVcpz viruses, whose inferred descendants have not been found in humans, still have the potential to cause a future HIV-1-like zoonotic outbreak.
Characterization of a Novel Conformational GII.4 Norovirus Epitope: Implications for Norovirus-Host Interactions
Authors: Carmona-Vicente Noelia , Vila-Vicent Susana , Allen David , Gozalbo-Rovira Roberto , Iturriza-Gómara Miren , Buesa Javier , Rodríguez-Díaz Jesús 
Published: June 2016

ABSTRACT
Human noroviruses (NoVs) are the main etiological agents of acute gastroenteritis worldwide. While NoVs are highly diverse (more than 30 genotypes have been detected in humans), during the last 40 years most outbreaks and epidemics have been caused by GII.4 genotype strains, raising questions about their persistence in the population. Among other potential explanations, immune evasion is considered to be a main driver of their success. In order to study antibody recognition and evasion in detail, we analyzed a conformational epitope recognized by a monoclonal antibody (3C3G3) by phage display, site-directed mutagenesis, and surface plasmon resonance. Our results show that the predicted epitope is composed of 11 amino acids within the P domain: P245, E247, I389, Q390, R397, R435, G443, Y444, P445, N446, and D448. Only two of them, R397 and D448, differ from the homologous variant (GII.4 Den-Haag_2006b) and from a previous variant (GII.4 VA387_1996) that is not recognized by the antibody. A double mutant derived from the VA387_1996 variant containing both changes, Q396R and N447D, is recognized by the 3C3G3 monoclonal antibody, confirming the participation of the two sites in the epitope recognized by the antibody. Furthermore, a single change, Q396R, is able to modify the histo-blood group antigen (HBGA) recognition pattern. These results provide evidence that the epitope recognized by the 3C3G3 antibody is involved in the virus-host interactions, both at the immunological and at the receptor levels.

IMPORTANCE
Human noroviruses are the main cause of viral diarrhea worldwide in people of all ages. Noroviruses can infect individuals who had been previously exposed to the same or different norovirus genotypes. Norovirus genotype GII.4 has been reported to be most prevalent during the last 40 years. In the present study, we describe a novel viral epitope identified by a monoclonal antibody and located within the highly diverse P domain of the capsid protein. The evolution of this epitope along with sequential GII.4 variants has allowed noroviruses to evade previously elicited antibodies, thus explaining how the GII.4 genotype can persist over long periods, reinfecting the population. Our results also show that the epitope participates in the recognition of host receptors that have evolved over time, as well.
Uranium irradiation history of carbonado diamond; implications for Paleoarchean oxidation in the São Francisco craton
Authors: Magee Charles W. , Teles Guilherme , Vicenzi Edward P. , Taylor Wayne , Heaney Peter 
Published: June 2016

Abstract
Carbonado is a porous polycrystalline diamond rock found in central African and Brazilian placer deposits. It contains unsupported radiogenic isotopes of He, Ne, Kr, Xe, and Pb. Here we show that these, and the radiation-related defects introduced to the diamond structure, are a result of uranium precipitation, with no isotopic or spectroscopic evidence of Th enrichment. The daughter products are unsupported due to Proterozoic U remobilization. Combining existing carbonado Pb isotope data with recent studies of the geochronology of the tectonic evolution of the São Francisco craton (eastern South America) reveals that the most likely scenario is Paleoarchean uranium enrichment of carbonado, followed by Mesoproterozoic uranium dissolution. Under all possible scenarios, the carbonado radiation damage history requires U mobilization in the Mesoarchean or late Paleoarchean. This is consistent with recent studies of South Africa and India Mesoarchean paleosols, which also show evidence for local oxygen activity greater than that of the Archean atmosphere and ocean. While those studies rely on whole-rock trace element and transition metal stable isotope measurements, this combination of crystallographic defects, sedimentary geochronology, and radiogenic isotopes supports the same conclusions of nonmarine, near-surface Archean oxygen enhancement.
Vegetation control allows autocyclic formation of multiple dunes on prograding coasts
Authors: Moore Laura J. , Vinent Orencio Durán , Ruggiero Peter 
Published: June 2016

Abstract
We investigate the formation of multiple dunes using a &gt;15 yr record of dune growth from Long Beach Peninsula, Washington State (USA), and a recently published coastal dune model modified to include a feedback between vegetation growth and local dune slope. In the presence of shoreline progradation, we find that multiple dune ridge formation can be autocyclic, arising purely from internal dune dynamics rather than requiring variations in external conditions. Our results suggest that the ratio of the shoreline progradation rate and the lateral dune growth rate is critical in determining the height, number, and form of multiple dunes, allowing the development of testable predictions. Our findings are consistent with observations and imply that caution is required when using dune ridges as proxies for past changes in climate, sea level, land use, and tectonic activity because the relationship between external events and the formation of multiple dunes may not be one to one as previously thought.
Effects of seafloor diagenesis on planktic foraminiferal radiocarbon ages
Authors: Wycech Jody , Kelly D. Clay , Marcott Shaun 
Published: June 2016

Abstract
Radiocarbon (14C) ages obtained from planktic foraminiferal calcite are a mainstay for reconstructing ocean-climate change and carbon cycle dynamics of the past 30 k.y., yet the effects of diagenesis on this vital chronometer are poorly constrained. Here, we address this shortcoming by comparing 14C ages and trace element ratios (Mg/Ca, Mn/Ca) of planktic foraminifera with white, opaque shells deemed well preserved by traditional standards to those with exquisitely preserved translucent shells. Results support a diagenetic mechanism as opaque shells yield 14C ages invariably older and trace element ratios consistently higher than those of translucent shells. Radiocarbon age offsets are particularly pronounced in mono-specific samples taken from stratigraphic horizons proximal to the δ18O maximum marking the Last Glacial Maximum (LGM) and the subsequent deglacial. Radiocarbon-based calendar ages of translucent shells from the two intervals are congruent with the established age ranges for these climate events, whereas those of co-occurring opaque shells overestimate the LGM and deglacial by 8–15 k.y. and 14–22 k.y., respectively. These results demonstrate that the use of translucent foraminifera enhances reproducibility and accuracy of 14C ages by minimizing the deleterious effects of diagenesis. This study serves as a cautionary tale since white, opaque foraminifera are common in pelagic sediments, and 14C ages derived from their ostensibly well-preserved shells can lead to discrepancies in the timing of Quaternary climate events and ocean circulation reconstructions.
High incidence of injury at the Sochi 2014 Winter Paralympic Games: a prospective cohort study of 6564 athlete days
Authors: Derman W , Schwellnus M P , Jordaan E , Runciman P , Van de Vliet P , Blauwet C , Webborn N , Willick S , Stomphorst J 
Published: June 2016

ObjectiveTo describe the epidemiology of injuries at the Sochi 2014 Winter Paralympic Games.MethodsA total of 547 athletes from 45 countries were monitored daily for 12 days during the Sochi 2014 Winter Paralympic Games (6564 athlete days). Daily injury data were obtained from teams with their own medical support (32 teams, 510 athletes) and teams without their own medical support (13 teams, 37 athletes) through electronic data capturing systems.ResultsThere were 174 total injuries reported, with an injury incidence rate (IR) of 26.5 per 1000 athlete days (95% CI 22.7% to 30.8%). There was a significantly higher IR recorded in alpine skiing/snowboarding (IR of 41.1 (95% CI 33.7% to 49.6%) p=0.0001) compared to cross-country skiing/biathlon, ice sledge hockey or wheelchair curling. Injuries in the shoulder region were the highest single-joint IR (IR of 6.4 (95% CI 4.6% to 8.6%)), although total upper and lower body IR were similar (IR 8.5 vs 8.4 (95% CI 6.4% to 11.1%)). Furthermore, the IR of acute injuries was significantly higher than other types of injury onset (IR of 17.8 (95% CI 14.7% to 21.4%)).ConclusionsIn a Winter Paralympic Games setting, athletes report higher injury incidence than do Olympic athletes or athletes in a Summer Paralympic Games setting. The highest incidence of injury was reported in the alpine skiing/snowboarding sporting category. There was a similar incidence of injury in the upper and lower limbs. The joint with the greatest rate of injury reported was the shoulder joint. Our data can inform injury prevention programmes and policy considerations regarding athlete safety in future Winter Paralympic Games.
The anticoagulation choices of internal medicine residents for stroke prevention in non-valvular atrial fibrillation
Authors: Moulson Nathaniel , McIntyre William F , Oqab Zardasht , Yazdan-Ashoori Payam , Quinn Kieran L , van Oosten Erik , Hopman Wilma M , Baranchuk Adrian 
Published: June 2016

ABSTRACTPurpose of the studyTo explore the oral anticoagulation (OAC) prescribing choices of Canadian internal medicine residents, at different training levels, in comparison with the Canadian Cardiovascular Society (CCS) guidelines for non-valvular atrial fibrillation (NVAF).Study designCross-sectional, web-based survey, involving clinical scenarios designed to favour the use of non-vitamin K antagonists (NOACs) as per the 2014 CCS NVAF guidelines. Additional questions were also designed to determine resident attitudes towards OAC prescribing.ResultsA total of 518 internal medicine responses were analysed, with 196 postgraduate year (PGY)-1s, 169 PGY-2s and 153 PGY-3s. The majority of residents (81%) reported feeling comfortable choosing OAC, with 95% having started OAC in the past 3 months. In the initial clinical scenario involving an uncomplicated patient with a CHADS2 score of 3, warfarin was favoured over any of the NOACs by PGY-1s (81.6% vs 73.9%), but NOACs were favoured by PGY-3s (88.3% vs 83.7%). This was the only scenario where OAC choices varied by PGY year, as each of the subsequent clinical scenarios residents generally favoured warfarin over NOACs irrespective of level of training. The majority of residents stated that they would no longer prescribe warfarin once NOAC reversal agents are available, and residents felt risk of adverse events was the most important factor when choosing OAC.ConclusionsCanadian internal medicine residents favoured warfarin over NOACs for patients with NVAF, which is in discordance with the evidence-based CCS guidelines. This finding persisted throughout the 3 years of core internal medicine training.
MultiLanes
Authors: Kang Junbin , Hu Chunming , Wo Tianyu , Zhai Ye , Zhang Benlong , Huai Jinpeng 
Published: June 2016

OS-level virtualization is often used for server consolidation in data centers because of its high efficiency. However, the sharing of storage stack services among the colocated containers incurs contention on shared kernel data structures and locks within I/O stack, leading to severe performance degradation on manycore platforms incorporating fast storage technologies (e.g., SSDs based on nonvolatile memories).
This article presents MultiLanes, a virtualized storage system for OS-level virtualization on manycores. MultiLanes builds an isolated I/O stack on top of a virtualized storage device for each container to eliminate contention on kernel data structures and locks between them, thus scaling them to manycores. Meanwhile, we propose a set of techniques to tune the overhead induced by storage-device virtualization to be negligible, and to scale the virtualized devices to manycores on the host, which itself scales poorly. To reduce the contention within each single container, we further propose SFS, which runs multiple file-system instances through the proposed virtualized storage devices, distributes all files under each directory among the underlying file-system instances, then stacks a unified namespace on top of them.
The evaluation of our prototype system built for Linux container (LXC) on a 32-core machine with both a RAM disk and a modern flash-based SSD demonstrates that MultiLanes scales much better than Linux in micro- and macro-benchmarks, bringing significant performance improvements, and that MultiLanes with SFS can further reduce the contention within each single container.
Reproductive Factors and Risk of Luminal, HER2-Overexpressing, and Triple-Negative Breast Cancer Among Multiethnic Women
Authors: Chen Lu , Li Christopher I. , Tang Mei-Tzu C. , Porter Peggy , Hill Deirdre A. , Wiggins Charles L. , Cook Linda S. 
Published: June 2016

Abstract
Background: Reproductive factors are among the most well-established risk factors for breast cancer. However, their associations with different breast cancer subtypes defined by joint estrogen receptor (ER)/progesterone receptor (PR)/HER2 status remain unclear.
Methods: We assessed relationships between reproductive factors and risks of luminal A (ER+/HER2−), luminal B (ER+/HER2+), triple-negative (TN; ER−/PR−/HER2−), and HER2-overexpressing (H2E; ER−/HER2+) breast cancers in a population-based case–case study consisting of 2,710 women ages 20–69 years diagnosed between 2004 and 2012. ORs and 95% confidence intervals (CI) were estimated with luminal A cases serving as the reference group using polytomous logistic regression.
Results: Earlier age at first full-term pregnancy and age at menopause were positively associated with odds of TN breast cancer (Ptrend: 0.003 and 0.024, respectively). Parity was associated with a 43% (95% CI, 1.08–1.89) elevated odds of H2E breast cancer, and women who had ≥3 full-term pregnancies had a 63% (95% CI, 1.16–2.29, Ptrend = 0.013) increased odds of this subtype compared with nulliparous women. Breast feeding for ≥36 months was associated with a 49% (OR 0.51; 95% CI, 0.27–0.99) lower odds of TN breast cancer.
Conclusion: Our results suggest that reproductive factors contribute differently to risks of the major molecular subtypes of breast cancer.
Impact: African American and Hispanic women have higher incidence rates of the more aggressive TN and H2E breast cancers and their younger average age at first pregnancy, higher parity, and less frequent breast feeding could in part contribute to this disparity. Cancer Epidemiol Biomarkers Prev; 25(9); 1297–304. ©2016 AACR.
Dysregulation of c-Myb Pathway by Aberrant Expression of Proto-oncogene MYB Provides the Basis for Malignancy in Adult T-cell Leukemia/lymphoma Cells
Authors: Nakano Kazumi , Uchimaru Kaoru , Utsunomiya Atae , Yamaguchi Kazunari , Watanabe Toshiki 
Published: June 2016

Abstract
Purpose: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive human T-cell malignancy induced by human T-lymphotrophic virus-1 (HTLV-1) infection. The genetic alterations in infected cells that lead to transformation have not been completely elucidated, thus hindering the identification of effective therapeutic targets for ATL. Here, we present the first assessment of MYB proto-oncogene dysregulation in ATL and an exploration of its role in the onset of ATL.
Experimental Design: We investigated the expression patterns of MYB splicing variants in ATL. The molecular characteristics of the c-Myb-9A isoform, which was overexpressed in ATL cells, were examined using chromatin immunoprecipitation and promoter assays. We further examined the biologic impacts of abnormal c-Myb overexpression in ATL using overall c-Myb knockdown with shRNA or c-Myb-9A knockdown with morpholino oligomers.
Results: Both total c-Myb and c-Myb-9A, which exhibited strong transforming activity, were overexpressed in ATL cells in a leukemogenesis- and progression-dependent manner. Knockdown of either total c-Myb or c-Myb-9A induced ATL cell death. c-Myb transactivates nine genes that encode essential regulators of cell proliferation and NF-κB signaling. c-Myb-9A induced significantly stronger transactivation of all tested genes and stronger NF-κB activation compared with wild-type c-Myb.
Conclusions: Our data demonstrate that c-Myb pathway overactivation caused by unbalanced c-Myb-9A overexpression is associated with disorders in cellular homeostasis and consequently, accelerated transformation, cell proliferation, and malignancy in ATL cells. These data support the notion of the c-Myb pathway as a promising new therapeutic target for ATL. Clin Cancer Res; 22(23); 5915–28. ©2016 AACR.
Prognostic Significance of Major Histocompatibility Complex Class II Expression in Pediatric Adrenocortical Tumors: A St. Jude and Children's Oncology Group Study
Authors: Pinto Emilia Modolo , Rodriguez-Galindo Carlos , Choi John Kim , Pounds Stanley , Liu Zhifa , Neale Geoffrey , Finkelstein David , Hicks John M. , Pappo Alberto S. , Figueiredo Bonald C. , Ribeiro Raul C. , Zambetti Gerard P. 
Published: June 2016

Abstract
Purpose: Histologic markers that differentiate benign and malignant pediatric adrenocortical tumors are lacking. Previous studies have implicated an association of MHC class II expression with adrenocortical tumor prognosis. Here, we determined the expression of MHC class II as well as the cell of origin of these immunologic markers in pediatric adrenocortical tumor. The impact of MHC class II gene expression on outcome was determined in a cohort of uniformly treated children with adrenocortical carcinomas.
Experimental Design: We analyzed the expression of MHC class II and a selected cluster of differentiation genes in 63 pediatric adrenocortical tumors by Affymetrix Human U133 Plus 2.0 or HT HG-U133+PM gene chip analyses. Cells expressing MHC class II were identified by morphologic and immunohistochemical assays.
Results: MHC class II expression was significantly greater in adrenocortical adenomas than in carcinomas (P = 4.8 ×10−6) and was associated with a higher progression-free survival (PFS) estimate (P = 0.003). Specifically, HLA-DPA1 expression was most significantly associated with PFS after adjustment for tumor weight and stage. HLA-DPA1 was predominantly expressed by hematopoietic infiltrating cells and undetectable in tumor cells in 23 of 26 cases (88%).
Conclusions: MHC class II expression, which is produced by tumor-infiltrating immune cells, is an indicator of disease aggressiveness in pediatric adrenocortical tumor. Our results suggest that immune responses modulate adrenocortical tumorigenesis and may allow the refinement of risk stratification and treatment for this disease. Clin Cancer Res; 22(24); 6247–55. ©2016 AACR.