tbuckley/cabot-search huggingface dataset:
Mitochondrial DNA evolution at a turtle's pace: evidence for low genetic variability and reduced microevolutionary rate in the Testudines.
Authors: J C Avise, B W Bowen, T Lamb, A B Meylan, E Bermingham
Journal: Molecular Biology and Evolution (1992)

Evidence is compiled suggesting a slowdown in mean microevolutionary rate for turtle mitochondrial DNA (mtDNA). Within each of six species or species complexes of Testudines, representing six genera and three taxonomic families, sequence divergence estimates derived from restriction assays are consistently lower than expectations based on either (a) the dates of particular geographic barriers with which significant mtDNA genetic clades appear associated or (b) the magnitudes of sequence divergence between mtDNA clades in nonturtle species that otherwise exhibit striking phylogeographic concordance with the genetic partitions in turtles. Magnitudes of the inferred rate slowdowns average eightfold relative to the "conventional" mtDNA clock calibration of 2%/Myr sequence divergence between higher animal lineages. Reasons for the postulated deceleration remain unknown, but two intriguing correlates are (a) the exceptionally long generation length most turtles and (b) turtles' low metabolic rate. Both factors have been suspected of influencing evolutionary rates in the DNA sequences of some other vertebrate groups. Uncertainities about the dates of cladogenetic events in these Testudines leave room for alternatives to the slowdown interpretation, but consistency in the direction of the inferred pattern, across several turtle species and evolutionary settings, suggests the need for caution in acceptance of a universal mtDNA-clock calibration for higher animals.
Fifty-Five-Year Personal Experience with Human Nutrition Worldwide
Authors: Nevin S. Scrimshaw
Journal: Annual Review of Nutrition (2007)

By 1950 the vitamins had been identified, but little was known of their functions. Beriberi, pellagra, and ariboflavinosis were disappearing, but kwashiorkor and/or marasmus were common in most developing countries. Requirements for protein were still uncertain, and those for essential amino acids or essential fatty acids were unknown. The author's contributions in the field of vitamins began in the 1950s and have been reported in more than 650 publications and in 20 books or monographs. These contributions include establishing the Institute of Nutrition of Central America and Panama, the Department of Nutrition and Food Science at the Massachusetts Institute of Technology, the World Hunger Program of the United Nations University, and the International Nutrition Foundation. His scientific contributions include identification of synergistic interactions of nutrition and infection, use of potassium iodate for fortifying crude moist salt, research in the epidemiology of kwashiorkor and marasmus, development of a successful low-cost protein-rich food for infants and young children, establishment of human protein requirements, and investigation of single-cell protein for food use.
A Randomized, Controlled Trial of Albumin versus Saline for the Treatment of Intradialytic Hypotension
Authors: Greg A. Knoll, Jenny A. Grabowski, Geoffrey F. Dervin, Keith O’Rourke
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Intradialytic hypotension (IDH) is the most common complication of hemodialysis. Symptomatic IDH requires the administration of fluid and often results in the early termination of dialysis, both of which may prevent adequate fluid removal. The optimal fluid for the treatment of IDH remains unknown. A randomized, double-blind, crossover trial was performed in 72 chronic hemodialysis patients to determine whether 5% albumin was more effective than normal saline for the treatment of IDH. The primary outcome measure was the percentage of target ultrafiltration achieved, which was defined as the actual ultrafiltration volume divided by target ultrafiltration volume. Secondary outcome measures included postdialysis BP, time to restore BP, recurrent IDH, and treatment failure (inability to restore BP with 750 ml of study fluid). The percentage of target ultrafiltration achieved was 0.84 ± 0.17 for 5% albumin compared with 0.80 ± 0.16 for saline (P = 0.14). The postdialysis systolic BP (121 ± 19 mmHg versus 117 ± 19 mmHg; P = 0.32), postdialysis diastolic BP (63 ± 9 mmHg versus 61 ± 9 mmHg; P = 0.33), volume of study fluid used to treat IDH (403 ± 170 ml versus 428 ± 191 ml; P = 0.34), time required to restore the BP (7.9 ± 6.6 min versus 9.9 ± 7.5 min; P = 0.09), total nursing time required to manage the hypotensive episode (15.1 ± 7.2 min versus 15.9 ± 7.3 min; P = 0.47), number of treatment failures (22% versus 24%; P = 1.0), and the frequency of recurrent IDH (36% versus 36%) were not significantly different when 5% albumin was used compared with saline. It is concluded that 5% albumin is no more effective than normal saline for the treatment of IDH in chronic hemodialysis patients. Normal saline should be used as the initial fluid for the treatment of IDH.
Pharmacokinetics and Pharmacodynamics of Insulin Glargine Given in the Evening as Compared With in the Morning in Type 2 Diabetes
Authors: Francesca Porcellati, Paola Lucidi, Patrizia Cioli, Paola Candeloro, Anna Marinelli Andreoli, Stefania Marzotti, Maura Ambrogi, Geremia B. Bolli, Carmine G. Fanelli
Journal: Diabetes Care (2014)

OBJECTIVE To compare pharmacokinetics (PK) and pharmacodynamics (PD) of insulin glargine in type 2 diabetes mellitus (T2DM) after evening versus morning administration. RESEARCH DESIGN AND METHODS Ten T2DM insulin-treated persons were studied during 24-h euglycemic glucose clamp, after glargine injection (0.4 units/kg s.c.), either in the evening (2200 h) or the morning (1000 h). RESULTS The 24-h glucose infusion rate area under the curve (AUC0–24h) was similar in the evening and morning studies (1,058 ± 571 and 995 ± 691 mg/kg × 24 h, P = 0.503), but the first 12 h (AUC0–12h) was lower with evening versus morning glargine (357 ± 244 vs. 593 ± 374 mg/kg × 12 h, P = 0.004), whereas the opposite occurred for the second 12 h (AUC12–24h 700 ± 396 vs. 403 ± 343 mg/kg × 24 h, P = 0.002). The glucose infusion rate differences were totally accounted for by different rates of endogenous glucose production, not utilization. Plasma insulin and C-peptide levels did not differ in evening versus morning studies. Plasma glucagon levels (AUC0–24h 1,533 ± 656 vs. 1,120 ± 344 ng/L/h, P = 0.027) and lipolysis (free fatty acid AUC0–24h 7.5 ± 1.6 vs. 8.9 ± 1.9 mmol/L/h, P = 0.005; β-OH-butyrate AUC0–24h 6.8 ± 4.7 vs. 17.0 ± 11.9 mmol/L/h, P = 0.005; glycerol, P &amp;lt; 0.020) were overall more suppressed after evening versus morning glargine administration. CONCLUSIONS The PD of insulin glargine differs depending on time of administration. With morning administration insulin activity is greater in the first 0–12 h, while with evening administration the activity is greater in the 12–24 h period following dosing. However, glargine PK and plasma C-peptide levels were similar, as well as glargine PD when analyzed by 24-h clock time independent of the time of administration. Thus, the results reflect the impact of circadian changes in insulin sensitivity in T2DM (lower in the night-early morning vs. afternoon hours) rather than glargine per se.
Combinatorial RNA interference in Caenorhabditis elegans reveals that redundancy between gene duplicates can be maintained for more than 80 million years of evolution
Authors: Julia Tischler, Ben Lehner, Nansheng Chen, Andrew G Fraser
Journal: Genome biology (2006)

Abstract Background Systematic analyses of loss-of-function phenotypes have been carried out for most genes in Saccharomyces cerevisiae , Caenorhabditis elegans , and Drosophila melanogaster . Although such studies vastly expand our knowledge of single gene function, they do not address redundancy in genetic networks. Developing tools for the systematic mapping of genetic interactions is thus a key step in exploring the relationship between genotype and phenotype. Results We established conditions for RNA interference (RNAi) in C. elegans to target multiple genes simultaneously in a high-throughput setting. Using this approach, we can detect the great majority of previously known synthetic genetic interactions. We used this assay to examine the redundancy of duplicated genes in the genome of C. elegans that correspond to single orthologs in S. cerevisiae or D. melanogaster and identified 16 pairs of duplicated genes that have redundant functions. Remarkably, 14 of these redundant gene pairs were duplicated before the divergence of C. elegans and C. briggsae 80-110 million years ago, suggesting that there has been selective pressure to maintain the overlap in function between some gene duplicates. Conclusion We established a high throughput method for examining genetic interactions using combinatorial RNAi in C. elegans . Using this technique, we demonstrated that many duplicated genes can retain redundant functions for more than 80 million years of evolution. This provides strong support for evolutionary models that predict that genetic redundancy between duplicated genes can be actively maintained by natural selection and is not just a transient side effect of recent gene duplication events.
Expression of thec-myc protooncogene product in cells infected with the hepatitis delta virus
Authors: Gianfranco Tappero, Gioacchino Natoli, Giovanni Anfossi, Floriano Rosina, Francesco Negro, Antonina Smedile, Ferruccio Bonino, Alberto Angeli, Robert H. Purcell, Professor Mario Rizzetto, Massimo Levrero
Journal: Hepatology (1994)

The intrahepatic accumulation of the c-myc protooncogene product was observed on immunofluorescence in each of six patients with chronic hepatitis delta virus infection who exhibited the hepatitis D antigen in their livers. The c-myc product was stained in the same nuclei that contained the hepatitis D antigen. C-myc was not observed in acute hepatitis D or in cases of chronic hepatitis delta virus infection without expression of the hepatitis D antigen. The protooncogene product was detected in only 1 of 32 viral and nonviral liver disorders unrelated to hepatitis delta virus. To confirm these observations, we transfected HBsAg-positive (PCL/PRF/5) and HBsAg-negative (HepG2) transformed liver cell lines with a plasmid containing a hepatitis delta virus cDNA trimer under the control of the SV40 early enhancer/promoter sequences. Whereas baseline c-myc expression was barely detectable in mock-transfected PLC/PRF/5 or HepG2 cells, strong c-myc nuclear fluorescence was observed when these same cells were transfected with the hepatitis D antigen expression vector. Similar results were obtained after infection of HeLa cells with a recombinant vaccinia virus expressing the hepatitis D antigen. Detection of c-myc mRNA sequences by means of in situ hybridization suggested that the c-myc product accumulation was not due to increased amounts of its mRNA. The c-myc protein accumulates selectively in the livers of patients with chronic hepatitis delta virus infection and in the same nuclei that contain the hepatitis D antigen. The expression of c-myc in hepatitis D antigen-containing cells does not require the presence of hepatitis B virus infection.
National homefill survey in Scotland
Authors: Phyllis Murphie, Mary Wilson, Willie McGhee, Stuart Little
Journal: European Respiratory Journal (2014)

In 2013 NHS Scotland transitioned to an integrated home oxygen service. The HomeFill oxygen system is a relatively new in Scotland and the demand for this modality is greater than was anticipated. The system combines an oxygen concentrator with an integrated reservoir allowing home refilling of ambulatory cylinders with integral oxygen conserving headsets. It provides a pulsed dose oxygen delivery option thus increasing the oxygen supply time by up to threefold.  Aims: 750 HomeFill users across 14 health boards were asked to complete a postal survey to seek their views on HomeFill.  Results: 450 surveys were returned/analysed representing a 62 % response. Respondents reported the system was easy to use with a 50% increase in time away from the home in those who went out 4 times or more per week. 92% of respondents reported improved quality of life and 100% rated the quality of the home care service service as good or better. A small number could not trigger the conserver device and appropriate initial assessment and review should determine capability to trigger the conserver system. One third of respondents indicated issues with the weight / duration of oxygen supply.  Conclusion: This is the largest HomeFill survey conducted and it indicates the vast majority find it easy to use and have benefitted from increased time away from home, improved quality of life, with additional home oxygen service improvement. It is a cost effective integrated Long term oxygen therapy / Ambulatory Oxygen system that is acceptable to the majority of patients who spend extended time away from home. HomeFill significantly reduces healthcare costs by eliminating cylinder deliveries, allowing users freedom and independence with an unlimited supply of ambulatory oxygen.
Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques
Authors: Takuya Hayashi, Shohei Wakao, Masaaki Kitada, Takayuki Ose, Hiroshi Watabe, Yasumasa Kuroda, Kanae Mitsunaga, Dai Matsuse, Taeko Shigemoto, Akihito Ito, Hironobu Ikeda, Hidenao Fukuyama, Hirotaka Onoe, Yasuhiko Tabata, Mari Dezawa
Journal: Journal of Clinical Investigation (2012)

A cell-based therapy for the replacement of dopaminergic neurons has been a long-term goal in Parkinson’s disease research. Here, we show that autologous engraftment of A9 dopaminergic neuron-like cells induced from mesenchymal stem cells (MSCs) leads to long-term survival of the cells and restoration of motor function in hemiparkinsonian macaques. Differentiated MSCs expressed markers of A9 dopaminergic neurons and released dopamine after depolarization in vitro. The differentiated autologous cells were engrafted in the affected portion of the striatum. Animals that received transplants showed modest and gradual improvements in motor behaviors. Positron emission tomography (PET) using [11C]-CFT, a ligand for the dopamine transporter (DAT), revealed a dramatic increase in DAT expression, with a subsequent exponential decline over a period of 7 months. Kinetic analysis of the PET findings revealed that DAT expression remained above baseline levels for over 7 months. Immunohistochemical evaluations at 9 months consistently demonstrated the existence of cells positive for DAT and other A9 dopaminergic neuron markers in the engrafted striatum. These data suggest that transplantation of differentiated autologous MSCs may represent a safe and effective cell therapy for Parkinson’s disease.
Enhanced Cortisol Suppression Following Dexamethasone Administration in Domestic Violence Survivors
Authors: Michael G. Griffin, Patricia A. Resick, Rachel Yehuda
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The authors compared responses of female domestic violence survivors and a matched group of nontraumatized participants to a low-dose (0.5 mg) dexamethasone suppression test (DST). METHOD: Seventy female domestic violence survivors and 14 nontraumatized women matched for age and race were recruited. Participants were assessed for trauma severity, severity of PTSD and depressive symptoms, and DST cortisol response. Of the domestic violence survivors who were DST-compliant, comparisons were made among those with PTSD (N=15), those with PTSD plus depression (N=27), and those with no PTSD or depression diagnosis (N=8) along with the nontraumatized comparison subjects (N=14). RESULTS: Domestic violence survivors with PTSD, regardless of whether or not they had comorbid depression, had significantly lower baseline cortisol levels at 9:00 a.m. than the healthy subjects and trauma survivors with no diagnosis. Survivors with a sole diagnosis of PTSD showed significantly greater cortisol suppression to dexamethasone than did healthy subjects or the group diagnosed with PTSD plus depression. CONCLUSIONS: These findings agree with previous studies showing hypothalamic-pituitary-adrenal (HPA) axis abnormalities in PTSD. The findings suggest that the chronic nature of domestic violence leads to a severe dysregulation of the HPA axis.
1049-105 Increased levels of Nt-ProANP and Nt-ProBrain natriuretic peptide as markers of cardiac depression in septic patiens
Authors: Ursula Hoffmann, Martina Brueckmann, Thomas Bertsch, Claudia Liebetrau, Martin Borggrefe, Guenter Huhle, Karl K Haase
Journal: Journal of the American College of Cardiology (2004)
Expression of the Steroid and Xenobiotic Receptor and Its Possible Target Gene, Organic Anion Transporting Polypeptide-A, in Human Breast Carcinoma
Authors: Yasuhiro Miki, Takashi Suzuki, Kunio Kitada, Nami Yabuki, Rie Shibuya, Takuya Moriya, Takanori Ishida, Noriaki Ohuchi, Bruce Blumberg, Hironobu Sasano
Journal: Cancer Research (2006)

Abstract Steroid and xenobiotic receptor (SXR) or human pregnane X receptor (hPXR) has been shown to play an important role in the regulation of genes related to xenobiotic detoxification, such as cytochrome P450 3A4 and multidrug resistance gene 1. Cytochrome P450 enzymes, conjugation enzymes, and transporters are all considered to be involved in the resistance of breast carcinoma to chemotherapeutic or endocrine agents. However, the expression of SXR/hPXR proteins and that of its target genes and their biological or clinical significance have not been examined in human breast carcinomas. Therefore, we first examined SXR/hPXR expression in 60 breast carcinomas using immunohistochemistry and quantitative reverse transcription-PCR. We then searched for possible SXR/hPXR target genes using microarray analysis of carcinoma cells captured by laser microscissors. SXR/hPXR was detected in carcinoma tissues but not in nonneoplastic and stromal cells of breast tumors. A significant positive correlation was detected between the SXR/hPXR labeling index and both the histologic grade and the lymph node status of the carcinoma cases. Furthermore, in estrogen receptor–positive cases, SXR/hPXR expression was also positively correlated with expression of the cell proliferation marker, Ki-67. Microarray analysis showed that organic anion transporting polypeptide-A (OATP-A) was most closely correlated with SXR/hPXR gene expression, and both OATP-A mRNA and protein were significantly associated with SXR/hPXR in both breast carcinoma tissues and its cell lines. These results suggest that SXR/hPXR and its target gene, such as OATP-A, may play important roles in the biology of human breast cancers. (Cancer Res 2006; 66(1): 535-42)
P element domestication: a stationary truncated P element may encode a 66-kDa repressor-like protein in the Drosophila montium species subgroup
Authors: D. Nouaud, D. Anxolabehere
Journal: Molecular Biology and Evolution (1997)

Functional P transposable elements can be separated into two distinct classes: mobile elements, which present the canonical structure, with transposase and repressor functions, and immobile P sequences truncated in 5' and 3' by loss of the terminal inverted repeats and exon 3, which retain only the repressor function. This second class was first described in some species of the Drosophila obscura group. Here, we describe a new truncated immobile P sequence cloned from one species of the Drosophila montium subgroup (D. tsacasi) that produces a polyadenylated RNA with a coding capacity for a 66-kDa "repressor-like" protein. The results from a number of different comparisons between P-homologous sequences concerning both coding and noncoding regions strongly suggest that the obscura and montium immobile P sequences as well as the T-type P subfamily derive from the same ancestral mobile P element family. Study of the flanking regions of these immobile P sequences shows that the two immobilizations were produced by two independent events. Our results provide evidence that the molecular domestication of a transposable element family may recur in a species lineage.
Influences of gamma interferon on synovial fibroblast-like cells. Ia induction and inhibition of collagen synthesis.
Authors: E P Amento, A K Bhan, K G McCullagh, S M Krane
Journal: Journal of Clinical Investigation (1985)

The shape and function of adherent cells cultured from rheumatoid synovial membranes are influenced by immune cells, and their products. The synovial cells produce collagenase and prostaglandin E2 (PGE2), the levels of which are increased when the cells are incubated with the monokine, mononuclear cell factor/interleukin 1. The majority of adherent synovial cells are fibroblastlike in appearance and synthesize collagens and fibronectin; the synthesis of collagens and fibronectins are also increased by a monocyte factor. In the present study we found that the fibroblastlike cells expressed major histocompatibility complex class II (Ia-like) antigens after initial dispersion from the synovial membrane. Monocyte lineage antigens were detected on some round cells in early passage, but no T lymphocytes were identified in established cultures. There was loss of Ia expression on the fibroblastlike cells with age and passage in culture. The addition of the lymphokine, gamma interferon (recombinant), induced class II antigen (DR and DS/DQ) expression in early or late passage cells in a time- and dose-dependent manner and required protein synthesis. Furthermore, the adherent synovial fibroblastlike cells continued to be Ia-positive when examined as long as 10 d after the removal of gamma interferon. Ia expression was also induced by gamma interferon in normal skin fibroblasts. Synovial cells that could be induced to express Ia also bound a monoclonal antibody to type III collagen (a fibroblast marker). Gamma interferon, while inducing Ia expression, decreased the binding of type III collagen antibody on unstimulated as well as monokine-stimulated cells. Analysis of [3H]proline-labeled medium by SDS polyacrylamide gel electrophoresis showed that gamma interferon decreased the synthesis of type I and III collagens and fibronectin by adherent synovial cells in a dose-dependent manner. These findings suggest that Ia expression by synovial tissue cells is not cell-specific, but reflects one or several related events, such as the degree of T lymphocyte infiltration, the presence of factors that stimulate gamma interferon release, or an increased sensitivity of the cells to gamma interferon. Whereas the synthesis of class II antigens is enhanced by the lymphokine gamma interferon, and a monocyte factor(s) stimulates collagen, collagenase and PGE2 synthesis by the same cells, gamma interferon inhibits basal and monokine-induced collagen synthesis. Thus, lymphokines and monokines may influence the extent of fibrosis as contrasted to matrix destruction at various stages of the rheumatoid lesion by affecting the function of fibroblastlike synovial cells.