tbuckley/cabot-search huggingface dataset:
Analysis of mammalian gene batteries reveals both stable ancestral cores and highly dynamic regulatory sequences
Authors: Laurence Ettwiller, Aidan Budd, François Spitz, Joachim Wittbrodt
Journal: Genome biology (2008)

Abstract Background Changes in gene regulation are suspected to comprise one of the driving forces for evolution. To address the extent of cis -regulatory changes and how they impact on gene regulatory networks across eukaryotes, we systematically analyzed the evolutionary dynamics of target gene batteries controlled by 16 different transcription factors. Results We found that gene batteries show variable conservation within vertebrates, with slow and fast evolving modules. Hence, while a key gene battery associated with the cell cycle is conserved throughout metazoans, the POU5F1 (Oct4) and SOX2 batteries in embryonic stem cells show strong conservation within mammals, with the striking exception of rodents. Within the genes composing a given gene battery, we could identify a conserved core that likely reflects the ancestral function of the corresponding transcription factor. Interestingly, we show that the association between a transcription factor and its target genes is conserved even when we exclude conserved sequence similarities of their promoter regions from our analysis. This supports the idea that turnover, either of the transcription factor binding site or its direct neighboring sequence, is a pervasive feature of proximal regulatory sequences. Conclusions Our study reveals the dynamics of evolutionary changes within metazoan gene networks, including both the composition of gene batteries and the architecture of target gene promoters. This variation provides the playground required for evolutionary innovation around conserved ancestral core functions.
Rel Induces Interferon Regulatory Factor 4 (<i>IRF-4</i>) Expression in Lymphocytes
Authors: Raelene J. Grumont, Steve Gerondakis
Journal: The Journal of Experimental Medicine (2000)

In lymphocytes, the Rel transcription factor is essential in establishing a pattern of gene expression that promotes cell proliferation, survival, and differentiation. Here we show that mitogen-induced expression of interferon (IFN) regulatory factor 4 (IRF-4), a lymphoid-specific member of the IFN family of transcription factors, is Rel dependent. Consistent with IRF-4 functioning as a repressor of IFN-induced gene expression, the absence of IRF-4 expression in c-rel−/− B cells coincided with a greater sensitivity of these cells to the antiproliferative activity of IFNs. In turn, enforced expression of an IRF-4 transgene restored IFN modulated c-rel−/− B cell proliferation to that of wild-type cells. This cross-regulation between two different signaling pathways represents a novel mechanism that Rel/nuclear factor κB can repress the transcription of IFN-regulated genes in a cell type–specific manner.
Successful treatment of topical photodynamic therapy using 5-aminolevulinic acid for plane warts
Authors: D. Mizuki, T. Kaneko, K. Hanada
Journal: British Journal of Dermatology (2003)

Journal Article Successful treatment of topical photodynamic therapy using 5‐aminolevulinic acid for plane warts Get access D. Mizuki, D. Mizuki Department of Dermatology, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan E‐mail: cooper@cc.hirosaki‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar T. Kaneko, T. Kaneko Department of Dermatology, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan E‐mail: cooper@cc.hirosaki‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar K. Hanada K. Hanada Department of Dermatology, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan E‐mail: cooper@cc.hirosaki‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue 5, 1 November 2003, Pages 1087–1088, https://doi.org/10.1111/j.1365-2133.2003.05617.x Published: 01 November 2003
Cross-kingdom patterns of alternative splicing and splice recognition
Authors: Abigail M McGuire, Matthew D Pearson, Daniel E Neafsey, James E Galagan
Journal: Genome biology (2008)

Variations in transcript splicing can reveal how eukaryotes recognize intronic splice sites. Retained introns (RIs) commonly appear when the intron definition (ID) mechanism of splice site recognition inconsistently identifies intron-exon boundaries, and cassette exons (CEs) are often caused by variable recognition of splice junctions by the exon definition (ED) mechanism. We have performed a comprehensive survey of alternative splicing across 42 eukaryotes to gain insight into how spliceosomal introns are recognized.All eukaryotes we studied exhibit RIs, which appear more frequently than previously thought. CEs are also present in all kingdoms and most of the organisms in our analysis. We observe that the ratio of CEs to RIs varies substantially among kingdoms, while the ratio of competing 3' acceptor and competing 5' donor sites remains nearly constant. In addition, we find the ratio of CEs to RIs in each organism correlates with the length of its introns. In all 14 fungi we examined, as well as in most of the 9 protists, RIs far outnumber CEs. This differs from the trend seen in 13 multicellular animals, where CEs occur much more frequently than RIs. The six plants we analyzed exhibit intermediate proportions of CEs and RIs.Our results suggest that most extant eukaryotes are capable of recognizing splice sites via both ID and ED, although ED is most common in multicellular animals and ID predominates in fungi and most protists.
Management of Cryptococcus gattii meningoencephalitis
Authors: Carlos Franco-Paredes, Tanea Womack, Teri Bohlmeyer, Brenda Sellers, Allison Hays, Kalpesh Patel, Jairo Lizarazo, Shawn R Lockhart, Wajid Siddiqui, Kieren A Marr
Journal: The Lancet Infectious Diseases (2014)
Studies on the pathogenesis of the pseudohermaphroditism in the mouse with testicular feminization
Authors: Joseph L. Goldstein, Jean D. Wilson
Journal: Journal of Clinical Investigation (1972)

The pathogenesis of the male pseudohermaphroditism in the mouse with X-linked testicular feminization (Tfm) has been investigated by comparing testosterone formation, the effects of androgen administration, and the metabolism of testosterone-1,2-(3)H in normal mice and Tfm mice of varying ages. First, it was established that the adult Tfm animal, in contrast to the human with testicular feminization, has both a low serum testosterone and a low rate of testosterone formation as assessed in slices of testes utilizing a variety of precursors. However, the formation of testosterone from pregnenolone-7alpha-(3)H was shown to be normal in newborn Tfm testes, suggesting that a defect in testosterone synthesis may not be primary to this mutation. Second, to establish that the pseudohermaphroditic state is due to androgen resistance rather than to diminished androgen biosynthesis during fetal life, the effect of the administration of dihydrotestosterone to pregnant animals was studied in male, female, and Tfm offspring. Whereas normal and carrier female littermates demonstrated striking virilization of the internal genital tract after such treatment, there was no sign of virilization in the Tfm animals. This finding provides direct experimental evidence in support of the view that male pseudohermaphroditism in testicular feminization is the result of resistance to androgen action during androgen-mediated sexual differentiation in embryos. Third, the metabolism of testosterone-1,2-(3)H was investigated both in tissue slices and in functionally hepatectomized animals. Dihydrotestosterone formation in tissue slices of the fetal anlage of the male organs of accessory reproduction is normal in the Tfm animal, suggesting that the primary defect in this disorder involves an intracellular event subsequent to this step and that the deficient dihydrotestosterone formation observed in the adult genital tract of the Tfm mouse is secondary to the failure of differentiation in these tissues. Finally, deficient binding of testosterone in the nuclei of the submandibular gland of adult Tfm animals, a known testosterone target tissue, was demonstrated in functionally hepatectomized mice. This finding could either be a manifestation of the primary genetic defect in this disorder or might reflect another acquired abnormality due to incomplete differentiation of adrogen-sensitive cell lines.
SEPARATION, CHARACTERIZATION, AND BIOLOGICAL SIGNIFICANCE OF A COMMON ANTIGEN IN ENTEROBACTERIACEAE
Authors: Calvin M. Kunin
Journal: The Journal of Experimental Medicine (1963)

An antigen common to Enterobacteriaceae and closely associated with endotoxin fractions has been separated by chromatography on DEAE cellulose employing elution with a NaCl gradient. The purified common antigen fails to coat erythrocytes, is poorly, if at all antigenic, it is non-dialyzable and excluded from sephadex G-100 gel. It is composed of polysaccharide and polypeptide. The most important property of this antigen thus far determined appears to be its interference with the specificity of the hemagglutination test commonly employed to measure antibody to O antigen of Enterobacteriaceae. It may also have taxonomic significance in classification of this family of bacteria.
The Obesity-Hypoventilation Syndrome in Siblings.
Authors: John S. Hanson
Journal: Annals of Internal Medicine (1964)

s1 April 1964The Obesity-Hypoventilation Syndrome in Siblings.John S. Hanson, M.D., F.A.C.P., Burton S. Tabakin, M.D., Herman L. Falsetti, M.D.John S. Hanson, M.D., F.A.C.P.Search for more papers by this author, Burton S. Tabakin, M.D.Search for more papers by this author, Herman L. Falsetti, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-4-719_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe occurrence of the obesity-hypoventilation syndrome with its characteristic features of obesity, cyanosis, somnolence, muscular twitching, and periodic breathing is documented for the first time in siblings. Severe respiratory insufficiency necessitated hospital admission for both brother and sister during the same week.Appropriate studies revealed extremely low respiratory tidal volumes of 200 ml and values for alveolar minute ventilation approximately one third of normal. Marked carbon dioxide retention was present in both cases, and although alveolar oxygen tensions were low on the basis of hypoventilation, large alveolar-arterial oxygen gradients existed. This was reflected in the arterial oxyhemoglobin saturations of 43... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: John S. Hanson, M.D., F.A.C.P.; Burton S. Tabakin, M.D.; Herman L. Falsetti, M.D.Affiliations: Burlington, Vermont PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1964Volume 60, Issue 4 Page: 719-719 Keywords Breathing Carbon dioxide Obesity Oxygen Pulse oximetry Respiratory failure Tidal volume ePublished: 1 December 2008 Issue Published: 1 April 1964 PDF downloadLoading ...
Pharmacokinetics of dasatinib for Philadelphia-positive acute lymphocytic leukemia with acquired T315I mutation
Authors: Naoto Takahashi, Masatomo Miura, Stuart A Scott, Takenori Niioka, Kenichi Sawada
Journal: Journal of Hematology & Oncology (2012)

The BCR-ABL T315I kinase domain mutation is insensitive to dasatinib therapy for Philadelphia-positive acute lymphoid leukemia (Ph + ALL) patients. Resistant T315I clone may be present prior to initiating dasatinib, which could expand under selective pressures during treatment. However, it is also possible that Ph + ALL patients newly acquire the T315I mutation during dasatinib therapy. Despite the potent inhibition of BCR-ABL kinase by dasatinib, little is known about the relationship between dasatinib pharmacokinetics and the emergence of kinase domain mutations in vivo. To determine whether plasma dasatinib pharmacokinetics influences the emergence of BCR-ABL mutations, we measured plasma dasatinib levels in 11 Ph + ALL patients undergoing dasatinib monotherapy. Bone marrow relapse occurred in 5 of the 11 Ph + ALL patients (45%). Importantly, a T315I mutation was detected in 4 of the 5 relapsed patients, despite the absence of BCR-ABL mutations in any patient at baseline. The median plasma concentration at 2 hours (C2h), the median plasma maximum concentration (Cmax), and the median area under the observed plasma concentration-time curve from 0 to 4 hours (AUC0-4) were all significantly lower in patients with T315I than those without the mutation (C2h, 22.3 ng/mL vs. 111.6 ng/mL, P = 0.0242; Cmax, 43.8 ng/mL vs. 112.4 ng/mL, P = 0.0242; AUC0-4, 108.3 ng·h/mL vs. 268.3 ng·h/mL, P = 0.0061, respectively). These data indicate that the emergence of the T315I mutation among Ph + ALL patients treated with dasatinib is, in part, dependent on plasma dasatinib pharmacokinetics. Notably, these data also suggest that newly acquired BCR-ABL mutations may be inhibited by an increased exposure of dasatinib.
Social class in asthma and allergic rhinitis: a national cohort study over three decades
Authors: L. Bråbäck, A. Hjern, F. Rasmussen
Journal: European Respiratory Journal (2005)

The aim of this study was to assess whether the association with social class differed between allergic rhinitis and asthma and whether these associations have changed over time. The Swedish Military Service Conscription Register was linked to two other national registers for 1,247,038 male conscripts in successive cohorts born between 1952 and 1977. The percentage of asthma cases associated with allergic rhinitis was 15% in the oldest cohort and 44% in the youngest cohort. Low socio-economic status (SES) was associated with an increased risk (assessed as odds ratio) of asthma without allergic rhinitis (1.14, 95% confidence interval (CI) 1.11–1.17) but a slightly reduced risk of asthma with allergic rhinitis (0.96, 95% CI 0.93–1.00). The risk of allergic rhinitis was 0.84, 95% CI 0.82–0.85. A positive interaction between SES and year of birth occurred in all three conditions. Low SES was related to a reduced risk of asthma with allergic rhinitis in the earliest cohort (0.72, 95% CI 0.53–0.82) but a slightly increased risk in the most recent cohort (1.07, 95% CI 1.01–1.14). In conclusion, the role of social class has changed over time. The steepest increase in asthma and allergic rhinitis occurred in conscripts with a low socio-economic status.
Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa
Authors: Carol J Loscher, Karsten Hokamp, Paul F Kenna, Alasdair C Ivens, Peter Humphries, Arpad Palfi, G Jane Farrar
Journal: Genome biology (2007)

The role played by microRNAs (miRs) as common regulators in physiologic processes such as development and various disease states was recently highlighted. Retinitis pigmentosa (RP) linked to RHO (which encodes rhodopsin) is the most frequent form of inherited retinal degeneration that leads to blindness, for which there are no current therapies. Little is known about the cellular mechanisms that connect mutations within RHO to eventual photoreceptor cell death by apoptosis.Global miR expression profiling using miR microarray technology and quantitative real-time RT-PCR (qPCR) was performed in mouse retinas. RNA samples from retina of a mouse model of RP carrying a mutant Pro347Ser RHO transgene and from wild-type retina, brain and a whole-body representation (prepared by pooling total RNA from eight different mouse organs) exhibited notably different miR profiles. Expression of retina-specific and recently described retinal miRs was semi-quantitatively demonstrated in wild-type mouse retina. Alterations greater than twofold were found in the expression of nine miRs in Pro347Ser as compared with wild-type retina (P < 0.05). Expression of miR-1 and miR-133 decreased by more than 2.5-fold (P < 0.001), whereas expression of miR-96 and miR-183 increased by more than 3-fold (P < 0.001) in Pro347Ser retinas, as validated by qPCR. Potential retinal targets for these miRs were predicted in silico.This is the first miR microarray study to focus on evaluating altered miR expression in retinal disease. Additionally, novel retinal preference for miR-376a and miR-691 was identified. The results obtained contribute toward elucidating the function of miRs in normal and diseased retina. Modulation of expression of retinal miRs may represent a future therapeutic strategy for retinopathies such as RP.
Screening for Hepatitis C Virus Infection in Adults: A Systematic Review for the U.S. Preventive Services Task Force
Authors: Roger Chou, Erika Barth Cottrell, Ngoc Wasson, Basmah Rahman, Jeanne-Marie Guise
Journal: Annals of Internal Medicine (2013)

Background: Identification of hepatitis C virus (HCV)–infected persons through screening could lead to interventions that improve clinical outcomes. Purpose: To review evidence about potential benefits and harms of HCV screening in asymptomatic adults without known liver enzyme abnormalities. Data Sources: English-language publications identified from MEDLINE (1947 to May 2012), the Cochrane Library Database, clinical trial registries, and reference lists. Study Selection: Randomized trials and cohort, case–control, and cross-sectional studies that assessed yield or clinical outcomes of screening; studies reporting harms from HCV screening; and large series reporting harms of diagnostic liver biopsies. Data Extraction: Multiple investigators abstracted and checked study details and quality by using predefined criteria. Data Synthesis: No study evaluated clinical outcomes associated with screening compared with no screening or of different risk- or prevalence-based strategies. Three cross-sectional studies in higher prevalence populations found that screening strategies that targeted multiple risk factors were associated with sensitivities greater than 90% and numbers needed to screen to identify 1 case of HCV infection of less than 20. Data on direct harms of screening were sparse. A large study of percutaneous liver biopsies (n = 2740) in HCV-infected patients with compensated cirrhosis reported no deaths and a 1.1% rate of serious adverse events (primarily bleeding and severe pain). Limitations: Modeling studies were not examined. High or unreported proportions of potentially eligible patients in the observational studies were not included in calculations of screening yield because of unknown HCV status. Conclusion: Although screening tests can accurately identify adults with chronic HCV infection, targeted screening strategies based on the presence of risk factors misses some patients with HCV infection. Well-designed prospective studies are needed to better understand the effects of different HCV screening strategies on diagnostic yield and clinical outcomes. Primary Funding Source: Agency for Healthcare Research and Quality.
Patient Adherence to Tuberculosis Treatment: A Systematic Review of Qualitative Research
Authors: Salla A Munro, Simon A Lewin, Helen J Smith, Mark E Engel, Atle Fretheim, Jimmy Volmink
Journal: PLoS Medicine (2007)

Tuberculosis (TB) is a major contributor to the global burden of disease and has received considerable attention in recent years, particularly in low- and middle-income countries where it is closely associated with HIV/AIDS. Poor adherence to treatment is common despite various interventions aimed at improving treatment completion. Lack of a comprehensive and holistic understanding of barriers to and facilitators of, treatment adherence is currently a major obstacle to finding effective solutions. The aim of this systematic review of qualitative studies was to understand the factors considered important by patients, caregivers and health care providers in contributing to TB medication adherence.
17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens.
Authors: G Girasole, R L Jilka, G Passeri, S Boswell, G Boder, D C Williams, S C Manolagas
Journal: Journal of Clinical Investigation (1992)

The effect of 17 beta-estradiol on interleukin-6 (IL-6) synthesis was examined in murine bone marrow-derived stromal cell lines, normal human bone-derived cells, and nontransformed osteoblast cell lines from mice and rats. In all these cell types IL-6 production was stimulated as much as 10,000-fold in response to the combination of recombinant interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). Addition of 17 beta-estradiol in the cultures exerted a dose-dependent inhibition of IL-1-, TNF-, and IL-1 + TNF-induced production of bioassayable IL-6. Testosterone and progesterone (but not 17 alpha-estradiol) also inhibited IL-6, but their effective concentrations were two orders of magnitude higher than 17 beta-estradiol. 17 beta-estradiol also decreased the levels of the IL-6 mRNA. In addition, estradiol inhibited both TNF-induced IL-6 production and osteoclast development in primary bone cell cultures derived from neonatal murine calvaria. The TNF-stimulated osteoclast development was also suppressed by a neutralizing monoclonal anti-IL-6 antibody. This in vitro evidence suggests, for the first time, a mechanistic paradigm by which estrogens might exert at least part of their antiresorptive influence on the skeleton.
Emotional Deprivation and Growth Retardation Simulating Idiopathic Hypopituitarism
Authors: G. F. Powell, J. A. Brasel, S. Raiti, R. M. Blizzard
Journal: New England Journal of Medicine (1967)

A DETAILED clinical account of 13 children with emotional deprivation and growth retardation simulating idiopathic hypopituitarism was presented in the preceding paper.1 All the children grew at remarkable rates when removed from their home environment. The present paper reports the endocrinologic evaluation of these children before and after a period of rapid growth.MethodsThyroid and Thyrotropic HormoneThyroid hormone and thyrotropic hormone (TSH) were evaluated by measurement of the protein-bound iodine (PBI)∥ concentration in the serum (normal, 4 to 8 μg. per 100 ml.)∥ and thyroxine (T4∥) by column or butanol extractable iodine (BEI)∥ (normal, 3.2 to . . .
Central pain mechanisms
Authors: R. H. De Jong
Journal: JAMA (1978)

Melzack who, with Wall,<sup>1</sup>introduced the "gate control" concept of pain some dozen years ago now has added important new insights toward a better understanding of chronic pain mechanisms. Together with Loeser,<sup>2</sup>he develops a hypothesis that explains puzzling observations about phantom body pain below the level of transection in paraplegic persons. Clearly, when all neural traffic between a body area and the brain is interrupted mechanically, impulse conduction along classic spinal pain tracts is halted. Yet, from 5% to 10% of paraplegics suffer severe discomfort from phantom body pain. Even more baffling, phantom body pain is experienced following cordectomy—the complete removal of one or more spinal cord segments. These are observations for which the segmental dorsal horn gate-control system theory provides less than satisfactory answers.<sup>3</sup> The severity of pain in paraplegic patients often leads to several attempts at deafferentation of the phantom body site with methods