tbuckley/cabot-search huggingface dataset:
Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques
Authors: Luca Micci, Emily S. Ryan, Rémi Fromentin, Steven E. Bosinger, Justin L. Harper, Tianyu He, Sara Paganini, Kirk A. Easley, Ann Chahroudi, Clarisse Benne, Sanjeev Gumber, Colleen S. McGary, Kenneth A. Rogers, Claire Deleage, Carissa Lucero, Siddappa N. Byrareddy, Cristian Apetrei, Jacob D. Estes, Jeffrey D. Lifson, Michael Piatak, Nicolas Chomont, Francois Villinger, Guido Silvestri, Jason M. Brenchley, Mirko Paiardini
Journal: Journal of Clinical Investigation (2015)

Despite successful control of viremia, many HIV-infected individuals given antiretroviral therapy (ART) exhibit residual inflammation, which is associated with non-AIDS-related morbidity and mortality and may contribute to virus persistence during ART. Here, we investigated the effects of IL-21 administration on both inflammation and virus persistence in ART-treated, SIV-infected rhesus macaques (RMs). Compared with SIV-infected animals only given ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and Th22 cells and a more effective reduction of immune activation in blood and intestinal mucosa, with the latter maintained through 8 months after ART interruption. Additionally, IL-21, in combination with ART, was associated with reduced levels of SIV RNA in plasma and decreased CD4(+) T cell levels harboring replication-competent virus during ART. At the latest experimental time points, which were up to 8 months after ART interruption, plasma viremia and cell-associated SIV DNA levels remained substantially lower than those before ART initiation in IL-21-treated animals but not in controls. Together, these data suggest that IL-21 supplementation of ART reduces residual inflammation and virus persistence in a relevant model of lentiviral disease and warrants further investigation as a potential intervention for HIV infection.
Anti‐cancer properties of anthraquinones from rhubarb
Authors: Qing Huang, Guodong Lu, Han‐Ming Shen, Maxey C.M. Chung, Choon Nam Ong
Journal: Medicinal Research Reviews (2006)

Abstract Rhubarb has been used as a traditional Chinese medicine since ancient times and today it is still present in various herbal preparations. In this review the toxicological and anti‐neoplastic potentials of the main anthraquinones from Rhubarb, Rheum palmatum, will be highlighted. It is interesting to note that although the chemical structures of various anthraquinones in this plant are similar, their bioactivities are rather different. The most abundant anthraquinone of rhubarb, emodin, was capable of inhibiting cellular proliferation, induction of apoptosis, and prevention of metastasis. These capabilities are reported to act through tyrosine kinases, phosphoinositol 3‐kinase (PI3K), protein kinase C (PKC), NF‐kappa B (NF‐κB), and mitogen‐activated protein kinase (MAPK) signaling cascades. Aloe‐emodin is another major component in rhubarb found to have anti‐tumor properties. Its anti‐proliferative property has been demonstrated to be through the p53 and its downstream p21 pathway. Our recent proteomic study also suggests that the molecular targets of these two anthraquinones are different. However, both components were found to be able to potentiate the anti‐proliferation of various chemotherapeutic agents. Rhein is the other major rhubarb anthraquinone, although less well studied. This compound could effectively inhibit the uptake of glucose in tumor cells, caused changes in membrane‐associated functions and led to cell death. Interestingly, all three major rhubarb anthraquinones were reported to have in vitro phototoxic. This re‐evaluation of an old remedy suggests that several bioactive anthraquinones of rhubarb possess promising anti‐cancer properties and could have a broad therapeutic potential. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 5, 609–630, 2007
Heart Defects in Connexin43-Deficient Mice
Authors: Jing Ya, Erna B. H. W. Erdtsieck-Ernste, Piet A. J. de Boer, Marjan J. A. van Kempen, Habo Jongsma, Daniel Gros, Antoon F. M. Moorman, Wouter H. Lamers
Journal: Circulation Research (1998)

Abstract —Cardiac malformation in connexin43 (CX43)-disrupted mice is restricted to the junction between right ventricle and outflow tract, even though CX43 is also expressed abundantly elsewhere. We analyzed cardiac morphogenesis in immunohistochemically and hybridohistochemically stained and three-dimensionally reconstructed serial sections of CX43-deficient embryos between embryonic day (ED) 10 and birth. The establishment of the D configuration in the ascending loop of CX43-deficient hearts is markedly retarded, so that the right ventricle retains a craniomedial position and is connected with the outflow tract by a more acute bend in ED10 and ED11 embryos. Because of the subsequent growth of the right ventricle, this condition usually evolves into a D loop, but when it persists, a “crisscross” configuration develops, with the atrioventricular cushions rotated 90°, a horizontal muscular ventricular septum, and a parallel course of the endocardial ridges of the outflow tract. After ED12, large intertrabecular pouches develop at the ventricular side of both shelflike myocardial structures that support the endocardial ridges of the outflow tract, ie, at the location that was earlier characterized by the acute bend between the right ventricle and the outflow tract and that subsequently develops into the anterosuperior leaflet of the tricuspid valve. Retarded development of the D configuration in the ascending loop of the embryonic heart predisposes the myocardium at the junction of the right ventricle and outflow tract to excessive development of intertrabecular pouches during subsequent development.
Screening for Pancreatic Cancer in High-Risk Individuals: A Call for Endoscopic Ultrasound
Authors: Alberto Larghi, Elizabeth C. Verna, Piera Giuseppina Lecca, Guido Costamagna
Journal: Clinical Cancer Research (2009)

Pancreatic cancer has a dismal prognosis, and early detection through screening is likely to be our best hope to improve survival. The relatively low incidence of pancreatic cancer and the insensitive screening techniques available currently render this approach prohibitively expensive and inefficient in the general population. Screening has begun, however, in the subset of patients at the highest risk of disease, such as those with inherited risk due to familial multiorgan cancer syndromes or in familial groupings of pancreatic cancer with yet unidentified genetic abnormalities, termed familial pancreatic cancer. Screening is currently done at several large centers in the world, each with a unique multidisciplinary approach and series of screening tests. Endoscopic ultrasound has emerged as the most promising imaging test given its high sensitivity and potential for tissue sampling. However, this potential to detect and cure early lesions should be carefully balanced with the risk of overtreatment, especially in view of the morbidity and mortality of pancreatic surgery. Additional experience to help determine the best screening strategy is greatly needed. Screening should therefore be done at experienced centers with multidisciplinary teams of specialists and in the context of research protocols.
Lysis of myotubes by alloreactive cytotoxic T cells and natural killer cells. Relevance to myoblast transplantation.
Authors: R Hohlfeld, A G Engel
Journal: Journal of Clinical Investigation (1990)

The aim of this study was to investigate the susceptibility of human myotubes to lysis by the two major types of cytotoxic effector cells, CD3+CD8+ cytotoxic T cells (CTL) and CD16+CD56+ natural killer (NK) cells. The myoblasts preparations used as target cells were greater than 90% pure as assessed by immunostaining with the Leu19 monoclonal antibody (MAb) that cross-reacts with the neural cell adhesion molecule N-CAM. Allospecific CTL lines were generated from mixed lymphocyte cultures, and freshly isolated allogeneic and autologous peripheral blood cells were used as a source of NK cells. The cytotoxicity was observed under phase optics and by immunoelectron microscopy, and was quantitated with a chromium release assay. Myotubes were efficiently killed by allospecific CTL and by autologous and allogeneic NK cells. The killing by CTL was inhibited with an anti-class I HLA MAb, and the killing by NK cells was inhibited by depleting peripheral blood cells of CD16+ cells with anti-CD16 MAb and complement. The results have important implications for myoblast transplantation, an experimental therapy of muscular dystrophy.
Ex vivo characterization of human CD8+ T subsets with distinct replicative history and partial effector functions
Authors: Nathalie Rufer, Alfred Zippelius, Pascal Batard, Mikaël J. Pittet, Isabel Kurth, Patricia Corthesy, Jean-Charles Cerottini, Serge Leyvraz, Eddy Roosnek, Markus Nabholz, Pedro Romero
Journal: Blood (2003)
Infant origins of childhood asthma associated with specific molds
Authors: Tiina Reponen, James Lockey, David I. Bernstein, Stephen J. Vesper, Linda Levin, Gurjit K. Khurana Hershey, Shu Zheng, Patrick Ryan, Sergey A. Grinshpun, Manuel Villareal, Grace LeMasters
Journal: Journal of Allergy and Clinical Immunology (2012)
Enigmatic Orthology Relationships between Hox Clusters of the African Butterfly Fish and Other Teleosts Following Ancient Whole-Genome Duplication
Authors: Kyle J Martin, Peter W H Holland
Journal: Molecular Biology and Evolution (2014)

Numerous ancient whole-genome duplications (WGD) have occurred during eukaryote evolution. In vertebrates, duplicated developmental genes and their functional divergence have had important consequences for morphological evolution. Although two vertebrate WGD events (1R/2R) occurred over 525 Ma, we have focused on the more recent 3R or TGD (teleost genome duplication) event which occurred approximately 350 Ma in a common ancestor of over 26,000 species of teleost fishes. Through a combination of whole genome and bacterial artificial chromosome clone sequencing we characterized all Hox gene clusters of Pantodon buchholzi, a member of the early branching teleost subdivision Osteoglossomorpha. We find 45 Hox genes organized in only five clusters indicating that Pantodon has suffered more Hox cluster loss than other known species. Despite strong evidence for homology of the five Pantodon clusters to the four canonical pre-TGD vertebrate clusters (one HoxA, two HoxB, one HoxC, and one HoxD), we were unable to confidently resolve 1:1 orthology relationships between four of the Pantodon clusters and the eight post-TGD clusters of other teleosts. Phylogenetic analysis revealed that many Pantodon genes segregate outside the conventional "a" and "b" post-TGD orthology groups, that extensive topological incongruence exists between genes physically linked on a single cluster, and that signal divergence causes ambivalence in assigning 1:1 orthology in concatenated Hox cluster analyses. Out of several possible explanations for this phenomenon we favor a model which keeps with the prevailing view of a single TGD prior to teleost radiation, but which also considers the timing of diploidization after duplication, relative to speciation events. We suggest that although the duplicated hoxa clusters diploidized prior to divergence of osteoglossomorphs, the duplicated hoxb, hoxc, and hoxd clusters concluded diploidization independently in osteoglossomorphs and other teleosts. We use the term "tetralogy" to describe the homology relationship which exists between duplicated sequences which originate through a shared WGD, but which diploidize into distinct paralogs from a common allelic pool independently in two lineages following speciation.
Convergence of the ZMIZ1 and NOTCH1 Pathways at C-MYC in Acute T Lymphoblastic Leukemias
Authors: Lesley A. Rakowski, Derek D. Garagiola, Choi M. Li, Margaret Decker, Sarah Caruso, Morgan Jones, Rork Kuick, Tomasz Cierpicki, Ivan Maillard, Mark Y. Chiang
Journal: Cancer Research (2012)

Activating NOTCH1 mutations are found in 50% to 60% of human T-cell acute lymphoblastic leukemia (T-ALL) samples. In mouse models, these mutations generally fail to induce leukemia. This observation suggests that NOTCH1 activation must collaborate with other genetic events. Mutagenesis screens previously implicated ZMIZ1 as a possible NOTCH1 collaborator in leukemia. ZMIZ1 is a transcriptional coactivator of the protein inhibitor of activated STAT (PIAS)-like family. Its role in oncogenesis is unknown. Here, we show that activated NOTCH1 and ZMIZ1 collaborate to induce T-ALL in mice. ZMIZ1 and activated NOTCH1 are coexpressed in a subset of human T-ALL patients and cell lines. ZMIZ1 inhibition slowed growth and sensitized leukemic cells to corticosteroids and NOTCH inhibitors. Gene expression profiling identified C-MYC, but not other NOTCH-regulated genes, as an essential downstream target of ZMIZ1. ZMIZ1 functionally interacts with NOTCH1 to promote C-MYC transcription and activity. The mechanism does not involve the NOTCH pathway and appears to be indirect and mediated independently of canonical PIAS functions through a novel N-terminal domain. Our study shows the importance of identifying genetic collaborations between parallel leukemic pathways that may be therapeutically targeted. They also raise new inquiries into potential NOTCH-ZMIZ1 collaboration in a variety of C-MYC-driven cancers.
Qualitative Environmental Health Research: An Analysis of the Literature, 1991–2008
Authors: Madeleine Kangsen Scammell
Journal: Environmental Health Perspectives (2010)

BackgroundRecent articles have advocated for the use of qualitative methods in environmental health research. Qualitative research uses nonnumeric data to understand people's opinions, motives, understanding, and beliefs about events or phenomena.ObjectiveIn this analysis of the literature, I report the use of qualitative methods and data in the study of the relationship between environmental exposures and human health.Data sourcesA primary search on ISI Web of Knowledge/Web of Science for peer-reviewed journal articles dated from 1991 through 2008 included the following three terms: qualitative, environ*, and health. Inclusion and exclusion criteria are described.Data extractionSearches resulted in 3,155 records. Data were extracted and findings of articles analyzed to determine where and by whom qualitative environmental health research is conducted and published, the types of methods and analyses used in qualitative studies of environmental health, and the types of information qualitative data contribute to environmental health.Data synthesisNinety-one articles met inclusion criteria. These articles were published in 58 different journals, with a maximum of eight for a single journal. The results highlight a diversity of disciplines and techniques among researchers who used qualitative methods to study environmental health, with most studies relying on one-on-one interviews. Details of the analyses were absent from a large number of studies. Nearly all of the studies identified increased scientific understanding of lay perceptions of environmental health exposures.Discussion and conclusionsQualitative data are published in traditionally quantitative environmental health studies to a limited extent. However, this analysis demonstrates the potential of qualitative data to improve understanding of complex exposure pathways, including the influence of social factors on environmental health, and health outcomes.
Mitogenomic Exploration of Higher Teleostean Phylogenies: A Case Study for Moderate-Scale Evolutionary Genomics with 38 Newly Determined Complete Mitochondrial DNA Sequences
Authors: Masaki Miya, Akira Kawaguchi, Mutsumi Nishida
Journal: Molecular Biology and Evolution (2001)

Although adequate resolution of higher-level relationships of organisms apparently requires longer DNA sequences than those currently being analyzed, limitations of time and resources present difficulties in obtaining such sequences from many taxa. For fishes, these difficulties have been overcome by the development of a PCR-based approach for sequencing the complete mitochondrial genome (mitogenome), which employs a long PCR technique and many fish-versatile PCR primers. In addition, recent studies have demonstrated that such mitogenomic data are useful and decisive in resolving persistent controversies over higher-level relationships of teleosts. As a first step toward resolution of higher teleostean relationships, which have been described as the "(unresolved) bush at the top of the tree," we investigated relationships using mitogenomic data from 48 purposefully chosen teleosts, of which those from 38 were newly determined during the present study (a total of 632,315 bp), using the above method. Maximum-parsimony and maximum-likelihood analyses were conducted with the data set that comprised concatenated nucleotide sequences from 12 protein-coding genes (excluding the ND6 gene and third codon positions) and 22 transfer RNA (tRNA) genes (stem regions only) from the 48 species. The resultant two trees from the two methods were well resolved and largely congruent, with many internal branches supported by high statistical values. The tree topologies themselves, however, exhibited considerable variation from the previous morphology-based cladistic hypotheses, with most of the latter being confidently rejected by the mitogenomic data. Such incongruence resulted largely from the phylogenetic positions or limits of long-standing problematic taxa, which were quite unexpected from previous morphological and molecular analyses. We concluded that the present study provided a basis of and guidelines for future investigations of teleostean evolutionary mitogenomics and that purposeful higher-density taxonomic sampling, subsequent sequencing efforts, and phylogenetic analyses of their mitogenomes may be decisive in resolving persistent controversies over higher-level relationships of teleosts, the most diversified group of all vertebrates, comprising over 23,500 extant species.
Genetic flux over time in the Salmonella lineage
Authors: Georgios S Vernikos, Nicholas R Thomson, Julian Parkhill
Journal: Genome biology (2007)

DNA sequences that are shared between closely related organisms while being absent from their common ancestor and from sister lineages of that ancestor are likely to have been acquired by horizontal gene transfer. Over time, the composition of those sequences tends to become more similar to the compositional signature of their host (amelioration). From a whole-genome comparative analysis of eleven Salmonella, three Escherichia coli and one Shigella strain, we inferred the relative time of insertion of putative horizontally acquired (PHA) genes in three Salmonella strains on different branches of the S. enterica phylogenetic tree. Compositional analysis suggests that most of the PHA genes are still undergoing an amelioration process and shows a clear correlation between time of insertion and the level of amelioration. The results show that older insertions include almost all functional classes. However, very recent horizontal transfer events in the Salmonella lineage involve primarily prophage elements that are shared only between very recently diverged lineages; despite this, the prophage sequence composition is close to that of the host, indicating that host adaptation, rather than amelioration, is likely to be the source of the compositional similarity. Almost half of the PHA genes were acquired at the base of the Salmonella lineage, whereas nearly three-quarters are shared between most S. enterica subspecies. The numerical distribution of PHA genes in the Salmonella tree topology correlates well with the divergence of the major Salmonella species, highlighting the major impact of horizontal transfer on the evolution of the salmonellae.
Diversification of Genes for Carotenoid Biosynthesis in Aphids following an Ancient Transfer from a Fungus
Authors: Eva Nováková, Nancy A. Moran
Journal: Molecular Biology and Evolution (2011)

The pea aphid genome was recently found to harbor genes for carotenoid biosynthesis, reflecting an ancestral transfer from a fungus. To explore the evolution of the carotene desaturase gene family within aphids, sequences were retrieved from a set of 34 aphid species representing numerous deeply diverging lineages of aphids and analyzed together with fungal sequences retrieved from databases. All aphids have at least one copy of this gene and some aphid species have up to seven, whereas fungal genomes consistently have a single copy. The closest relatives of aphids, adelgids, also have carotene desaturase; these sequences are most closely related to those from aphids, supporting a shared origin from a fungal to insect transfer predating the divergence of adelgids and aphids. Likewise, all aphids, and adelgids, have carotenoid profiles that are consistent with their biosynthesis using the acquired genes of fungal origin rather than derivation from food plants. The carotene desaturase was acquired from a fungal species outside of Ascomycota or Basidiomycota and closest to Mucoromycotina among sequences available in databases. In aphids, an ongoing pattern of gene duplication is indicated by the presence of both anciently and recently diverged paralogs within genomes and by the presence of a high frequency of pseudogenes that appear to be recently inactivated. Recombination among paralogs is evident, making analyses of patterns of selection difficult, but tests of selection for a nonrecombining region indicates that duplications tend to be followed by bouts of positive selection. Species of Macrosiphini, which often show color polymorphisms, typically have a larger number of desaturase copies relative to other species sampled in the study. These results indicate that aphid evolution has been accompanied by ongoing evolution of carotenogenic genes, which have undergone duplication, recombination, and occasional positive selection to yield a wide variety of carotenoid profiles in different aphid species.
IMMUNOGLOBULIN D AS A LYMPHOCYTE RECEPTOR
Authors: David S. Rowe, Katharina Hug, Luciana Forni, Benvenuto Pernis
Journal: The Journal of Experimental Medicine (1973)

A large proportion of the human peripheral blood lymphocytes of adults and newborns having IgD were found also to have IgM on their membranes and vice versa. A few lymphocytes had one of these classes only. IgD and IgM could be capped independently on the same cell. The possibility that IgD was acquired by a cytophilic process was excluded by the finding that IgD-bearing cells were of one light chain type only, and by the direct demonstration of reappearance of IgD on the lymphocyte membrane during incubation in an IgD-free culture medium. On the basis of these findings, it is proposed that IgD functions as a lymphocyte antigen receptor.