UFGI Publications Round-Up Week 8/1/2016
HIV maintains an evolving and dispersed population among multiple tissues during suppressive cART with periods of rapid expansion corresponding to the onset of cancer.
Author information: Rose R1, Lamers SL1, Nolan DJ2, Maidji E3, Faria NR4, Pybus OG4, Dollar JJ5, Maruniak SA5, McAvoy AC5, Salemi M5, Stoddart C3, Singer E6, McGrath MS7.
1Bioinfoexperts, LLC, Thibodaux, LA, USA 70302.
2Bioinfoexperts, LLC, Thibodaux, LA, USA 70302. Department of Pathology, Immunology and Laboratory Medicine and the Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA 32610.
3Department of Laboratory Medicine, Pathology, and Medicine, University of California at San Francisco, CA, USA 94143.
4Department of Zoology, University of Oxford, Oxford, UK OX13PS.
5Department of Pathology, Immunology and Laboratory Medicine and the Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA 32610.
6The National Neurological AIDS Bank at the University of California at Los Angeles, CA, USA 90095.
7Department of Laboratory Medicine, Pathology, and Medicine, University of California at San Francisco, CA, USA 94143. The AIDS and Cancer Specimen Resource, University of California at San Francisco, CA 94143, USA. MMcGrath@php.ucsf.edu.
Journal: Journal of Virology
Date of e-pub: July 27, 2016
Abstract: While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious co-morbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies.We obtained DNA and RNA env, nef and pol sequences using single genome sequencing from post mortem tissues of three HIV+/cART+ individuals with undetectable viral load and metastatic cancer at death, and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient.Tissue-associated virus evolved at a similar rate in cART+ and cART- patients. Phylogenetic trees were characterized by two distinct features: 1) branching patterns consistent with constant viral evolution and dispersal amongst tissues; and 2) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Cancer diagnoses were temporally associated with diversification of viral lineages. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA+ cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV-expressing cells.Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread.
IMPORTANCE: Combined anti-retroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. Here, we isolated and sequenced HIV from post mortem tissues from three HIV+/cART+ individuals who died with metastatic cancer and had no detectable plasma viral load. Using high-resolution evolutionary analyses, we found that tissue-based HIV continues to replicate, evolve and migrate among tissues during cART. Furthermore, cancer onset and metastasis coincided with increased HIV diversity, suggesting a linked mechanism. HIV-expressing cells were associated with tissue macrophages, a target of HIV infection. Our results suggest the importance of tissues, and macrophages in particular, as a target for novel anti-HIV therapies.
HIV DNA is frequently present within pathologic tissues evaluated at autopsy from cART-treated patients with undetectable viral load.
Author information: Lamers SL1, Rose R1, Maidji E2, Agsalda-Garcia M3, Nolan DJ4, Fogel GB5, Salemi M6, Garcia DL7, Bracci P7, Yong W8, Commins D9, Said J8, Khanlou N8,Hinkin CH10, Valdes Sueiras M11, Mathisen G12, Donovan S12, Shirimizu B3, Stoddart CA2, McGrath MS13, Singer EJ11.
1Bioinfoexperts, LLC, Thibodaux, LA, USA.
2Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, USA.
3The University of Hawaii, Department of Tropical Medicine, Medical Microbiology & Pharmacology and Hawaii Center for AIDS, USA.
4Bioinfoexperts, LLC, Thibodaux, LA, USA The University of Florida Emerging Pathogens Institute, Department of Pathology and Laboratory Medicine, Gainesville, FL.
5Natural Selection, Inc., San Diego, CA, USA.
6The University of Florida Emerging Pathogens Institute, Department of Pathology and Laboratory Medicine, Gainesville, FL.
7The AIDS and Cancer Specimen Resource, San Francisco, CA, USA The University of California, San Francisco, Department of Medicine, San Francisco, CA, USA.
8The National Neurological AIDS Bank at the University of California at Los Angeles, USA David Geffen School of Medicine and Olive View-UCLA Medical Center, Department of Pathology and Laboratory Medicine, Los Angeles USA.
9;University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
10The National Neurological AIDS Bank at the University of California at Los Angeles, USA UCLA School of Medicine, Department of Psychiatry & Biobehavioral Sciences, Los Angeles, CA, USA.
11The National Neurological AIDS Bank at the University of California at Los Angeles, USA David Geffen School of Medicine and Olive View-UCLA Medical Center, Department of Neurology.
12The National Neurological AIDS Bank at the University of California at Los Angeles, USA.
13The AIDS and Cancer Specimen Resource, San Francisco, CA, USA The University of California, San Francisco, Department of Medicine, San Francisco, CA, USA MMcGrath@php.ucsf.edu.
Journal: Journal of Virology
Date of e-pub: July 27, 2016
Abstract: HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV+/cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death, who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and non-brain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 non-brain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta and kidney. All brain tissues demonstrated some degree of pathology. 95% of participants had some degree of atherosclerosis and 75% of participants died with cancer. This study assists in characterizing the anatomic locations of HIV, in particular, macrophage-rich tissues, such as CNS and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis.
IMPORTANCE: It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An on-going question is, “Where is HIV hiding?” A well-studied HIV reservoir are “resting” T-cells, which can be isolated from blood products and succumb to cART once activated. Less studied reservoirs are anatomical tissue samples, which have unknown cART penetration, contain a comparably diverse spectrum of potentially HIV-infected immune cells, and are important since < 2% of body lymphocytes actually reside in blood. We examined 229 varied autopsy specimens from 20 HIV+ participants who died while on cART and identified that >50% of tissues were HIV-infected. Additionally, we identified considerable pathology in participants’ tissues, especially in brain, spleen, lung, lymph node, liver, aorta and kidney. This study substantiates that tissue-associated HIV is present despite cART and can inform future studies into HIV persistence.
A single amino acid (Asp159) from the dog prion protein suppresses the toxicity of the mouse prion protein in Drosophila.
Author information: Sanchez-Garcia J1, Jensen K1, Zhang Y1, Rincon-Limas DE2, Fernandez-Funez P3.
1McKnight Brain Institute, Department of Neurology, University of Florida, Gainesville, FL 32611, United States.
2McKnight Brain Institute, Department of Neurology, University of Florida, Gainesville, FL 32611, United States; Department of Neuroscience, Genetics Institute and Center for Translational Research on Neurodegenerative Disorders, University of Florida, Gainesville, FL 32611, United States.
3McKnight Brain Institute, Department of Neurology, University of Florida, Gainesville, FL 32611, United States; Department of Neuroscience, Genetics Institute and Center for Translational Research on Neurodegenerative Disorders, University of Florida, Gainesville, FL 32611, United States. Electronic address: pedro.ffunez@gmail.com.
Journal: Neurobiology of Disease
Date of e-pub: July 28, 2016
Abstract: Misfolding of the prion protein (PrP) is the key step in the transmission of spongiform pathologies in humans and several animals. Although PrP is highly conserved in mammals, a few changes in the sequence of endogenous PrP are proposed to confer protection to dogs, which were highly exposed to prion during the mad-cow epidemics. D159 is a unique amino acid found in PrP from dogs and other canines that was shown to alter surface charge, but its functional relevance has never been tested in vivo. Here, we show in transgenic Drosophila that introducing the N159D substitution on mouse PrP decreases its turnover. Additionally, mouse PrP-N159D demonstrates no toxicity and accumulates no pathogenic conformations, suggesting that a single D159 substitution is sufficient to prevent PrP conformational change and pathogenesis. Understanding the mechanisms mediating the protective activity of D159 is likely to lessen the burden of prion diseases in humans and domestic animals.
The C/ebp-Atf response element (CARE) location reveals two distinct Atf4-dependent, elongation-mediated mechanisms for transcriptional induction of aminoacyl-tRNA synthetase genes in response to amino acid limitation.
Author information: Shan J1, Zhang F1, Sharkey J1, Tang TA1, Kilberg MS2.
1Department of Biochemistry and Molecular Biology, Shands Cancer Center and Center for Nutritional Sciences, University of Florida College of Medicine, Gainesville, FL 32610, USA.
2Department of Biochemistry and Molecular Biology, Shands Cancer Center and Center for Nutritional Sciences, University of Florida College of Medicine, Gainesville, FL 32610, USA mkilberg@ufl.edu.
Journal: Nucleic Acids Research
Date of e-pub: July 28, 2016
Abstract: The response to amino acid (AA) limitation of the entire aminoacyl-tRNA synthetase (ARS) gene family revealed that 16/20 of the genes encoding cytoplasmic-localized enzymes are transcriptionally induced by activating transcription factor 4 (Atf4) via C/ebp-Atf-Response-Element (CARE) enhancers. In contrast, only 4/19 of the genes encoding mitochondrial-localized ARSs were weakly induced. Most of the activated genes have a functional CARE near the transcription start site (TSS), but for others the CARE is downstream. Regardless of the location of CARE enhancer, for all ARS genes there was constitutive association of RNA polymerase II (Pol II) and the general transcription machinery near the TSS. However, for those genes with a downstream CARE, Atf4, C/ebp-homology protein (Chop), Pol II and TATA-binding protein exhibited enhanced recruitment to the CARE during AA limitation. Increased Atf4 binding regulated the association of elongation factors at both the promoter and the enhancer regions, and inhibition of cyclin-dependent kinase 9 (CDK9), that regulates these elongation factors, blocked induction of the AA-responsive ARS genes. Protein pull-down assays indicated that Atf4 directly interacts with CDK9 and its associated protein cyclin T1. The results demonstrate that AA availability modulates the ARS gene family through modulation of transcription elongation.
The tale of the shrinking weapon: seasonal changes in nutrition affect weapon size and sexual dimorphism, but not contemporary evolution.
Author information: Miller CW1, McDonald GC2, Moore AJ3.
1Entomology and Nematology Department, University of Florida, P.O. Box 110620, Gainesville, FL, 32611, USA.
2Edward Grey Institute, Department of Zoology, University of Oxford, Oxford, UK.
3Department of Genetics, University of Georgia, Athens, GA, 30602, USA.
Journal: Journal of Evolutionary Biology
Date of e-pub: July 28, 2016
Abstract: Sexually-selected traits are often highly variable in size within populations due to their close link with the physical condition of individuals. Nutrition has a large impact on physical condition, and thus any seasonal changes in nutritional quality are predicted to alter the average size of sexually-selected traits as well as the degree of sexual dimorphism in populations. However, while traits affected by mate choice are well-studied, we have a surprising lack of knowledge of how natural variation in nutrition affects the expression of sexually-selected weapons and sexual dimorphism. Further, few studies explicitly test for differences in the heritability and mean-scaled evolvability of sexually-selected traits across conditions. Using the insect, Narnia femorata (Hemiptera: Coreidae), an insect where males use their hind legs as weapons and the femurs are enlarged, we studied the extent to which weapon expression, sexual dimorphism, and evolvability change across the actual range of nutrition available in the wild. We found that insects raised on a poor diet (cactus without fruit) are nearly monomorphic, while those raised on a high quality diet (cactus with ripe fruit) are distinctly sexually dimorphic via the expression of large hind leg weapons in males. Contrary to our expectations, we found little evidence of a potential for evolutionary change for any trait measured. Thus, although we show weapons are highly condition dependent, and changes in weapon expression and dimorphism could alter evolutionary dynamics, our populations are unlikely to experience further evolutionary changes under current conditions.
Gene Expression Profiling in Fish Toxicology: A Review.
Author information: Kumar G1, Denslow ND2.
1Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, University of South Bohemia in Ceske Budejovice, Zátiší 728/II, 389 25, Vodňany, Czech Republic. girishkumar.nio@gmail.com.
2Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611, USA.
Journal: Reviews of Environmental Contamination and Toxicology
Date of e-pub: July 28, 2016
Abstract: In this review, we present an overview of transcriptomic responses to chemical exposures in a variety of fish species. We have discussed the use of several molecular approaches such as northern blotting, differential display reverse transcription-polymerase chain reaction (DDRT-PCR), suppression subtractive hybridization (SSH), real time quantitative PCR (RT-qPCR), microarrays, and next-generation sequencing (NGS) for measuring gene expression. These techniques have been mainly used to measure the toxic effects of single compounds or simple mixtures in laboratory conditions. In addition, only few studies have been conducted to examine the biological significance of differentially expressed gene sets following chemical exposure. Therefore, future studies should focus more under field conditions using a multidisciplinary approach (genomics, proteomics and metabolomics) to understand the synergetic effects of multiple environmental stressors and to determine the functional significance of differentially expressed genes. Nevertheless, recent developments in NGS technologies and decreasing costs of sequencing holds the promise to uncover the complexity of anthropogenic impacts and biological effects in wild fish populations.
Raising Awareness: The Need to Promote Allocation of Pancreata from Rare Non-Diabetic Donors with Pancreatic Islet Autoimmunity to Type 1 Diabetes Research.
Author information: Burke GW 3rd1,2, Posgai AL3, Wasserfall CH3, Atkinson MA3, Pugliese A1,4,5.
1Diabetes Research Institute, University of Miami Miller School of Medicine.
2Department of Surgery, University of Miami Miller School of Medicine.
3Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL, 32610.
4Departments of Medicine, University of Miami Miller School of Medicine.
5Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, 33136.
Journal: American Journal of Transplantation
Date of e-pub: July 26, 2016
Abstract: We would like to engage the transplant community and ask support for research about the causes of type 1 diabetes (T1D): we discuss here the critical need to facilitate allocation to research of pancreata from those rare organ donors with recent onset T1D or prediabetes.
Mechanistic insight into protein modification and sulfur mobilization activities of noncanonical E1 and associated ubiquitin-like proteins of Archaea.
Author information: Hepowit NL1, de Vera IM2, Cao S1, Fu X1, Wu Y1, Uthandi S1, Chavarria NE1, Englert M3, Su D3, Sӧll D3,4, Kojetin DJ2, Maupin-Furlow JA1,5.
1Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences.
2Department of Molecular Therapeutics, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458.
3Department of Molecular Biophysics and Biochemistry.
4Department of Chemistry, Yale University, New Haven, CT, 06511.
5Genetics Institute, University of Florida, Gainesville, Florida, 32611.
Journal: The FEBS Journal
Date of e-pub: July 26, 2016
Abstract: Here we provide the first detailed biochemical study of a noncanonical E1-like enzyme with broad specificity for cognate ubiquitin-like (Ubl) proteins that mediates Ubl protein modification and sulfur mobilization to form molybdopterin and thiolated tRNA. Isothermal titration calorimetry and in vivo analyses proved useful in discovering that environmental conditions, ATP binding and Ubl type controlled the mechanism of association of the Ubl protein with its cognate E1-like enzyme (SAMP and UbaA of the archaeon Haloferax volcanii, respectively). Further analysis revealed ATP hydrolysis triggered the formation of thioester and peptide bonds within the Ubl:E1-like complex. Importantly, the thioester was an apparent precursor to Ubl protein modification but not sulfur mobilization. Comparative modeling to MoeB/ThiF guided the discovery of key residues within the adenylation domain of UbaA that were needed to bind ATP as well as residues that were specifically needed to catalyze the downstream reactions of sulfur mobilization and/or Ubl protein modification. UbaA was also found to be Ubl-automodified at lysine residues required for early (ATP binding) and late (sulfur mobilization) stages of enzyme activity revealing multiple layers of auto-regulation. Cysteine residues, distinct from the canonical E1 ‘active site’ cysteine, were found important in UbaA function supporting a model that this non-canonical E1 is structurally flexible in its active site to allow Ubl~adenylate, Ubl~E1-like thioester and cysteine persulfide(s) intermediates to form.
Kin of coauthorship in five decades of health science literature.
Author information: Prosperi M1, Buchan I2, Fanti I3, Meloni S4, Palladino P5, Torvik VI6.
1Department of Epidemiology, College of Public Health and Health Professions, University of Florida, Gainesville, FL 32610; Department of Epidemiology, College of Medicine, University of Florida, Gainesville, FL 32610; Centre for Health Informatics, Institute of Population Health, University of Manchester, Manchester M13 9PL, United Kingdom; m.prosperi@phhp.ufl.edu.
2Centre for Health Informatics, Institute of Population Health, University of Manchester, Manchester M13 9PL, United Kingdom;
3Infectious Diseases Clinic, Catholic University of the Sacred Heart, Rome 00168, Italy;
4Institute for Biocomputation and Physics of Complex Systems, University of Zaragoza, Zaragoza 50018, Spain; Department of Theoretical Physics, University of Zaragoza, Zaragoza 50009, Spain;
5Genomics, Genetics and Biology Innovation Pole, Perugia 06134, Italy;
6Graduate School of Library and Information Science, University of Illinois at Urbana-Champaign, Champaign, IL 61820.
Journal: Proceedings of the National Academies of Sciences
Date of e-pub: July 25, 2016
Abstract: Family background-kinship-can propagate careers. The evidence for academic nepotism is littered with complex associations and disputed causal inferences. Surname clustering, albeit with very careful consideration of surnames’ flows across regions and time periods, can be used to reflect family ties. We examined surname patterns in the health science literature, by country, across five decades. Over 21 million papers indexed in the MEDLINE/PubMed database were analyzed. We identified relevant country-specific kinship trends over time and found that authors who are part of a kin tend to occupy central positions in their collaborative networks. Just as kin build potent academic networks with their own resources, societies may do well to provide equivalent support for talented individuals with fewer resources, on the periphery of networks.
Transcriptional networks associated with the immune system are disrupted by organochlorine pesticides in largemouth bass (Micropterus salmoides) ovary.
Author information: Martyniuk CJ1, Doperalski NJ2, Feswick A2, Prucha MS2, Kroll KJ2, Barber DS2, Denslow ND2.
1Department of Physiological Sciences and Center for Environmental and Human Toxicology and Genetics Institute, University of Florida,Gainesville, FL 32611 USA. Electronic address: cmartyn@ufl.edu.
2Department of Physiological Sciences and Center for Environmental and Human Toxicology and Genetics Institute, University of Florida,Gainesville, FL 32611 USA.
Journal: Aquatic Toxicology
Date of e-pub: August 2016
Abstract: Largemouth bass (Micropterus salmoides) inhabiting Lake Apopka, Florida are exposed to high levels of persistent organochlorine pesticides (OCPs) and dietary uptake is a significant route of exposure for these apex predators. The objectives of this study were to determine the dietary effects of two organochlorine pesticides (p, p’-dichlorodiphenyldichloroethylene; p, p’ DDE and methoxychlor; MXC) on the reproductive axis of largemouth bass. Reproductive bass (late vitellogenesis) were fed one of the following diets: control pellets, 125ppm p, p’-DDE, or 10ppm MXC (mg/kg) for 84days. Due to the fact that both p,p’ DDE and MXC have anti-androgenic properties, the anti-androgenic pharmaceutical flutamide was fed to a fourth group of largemouth bass (750ppm). Following a 3 month exposure, fish incorporated p,p’ DDE and MXC into both muscle and ovary tissue, with the ovary incorporating 3 times more organochlorine pesticides compared to muscle. Endpoints assessed were those related to reproduction due to previous studies demonstrating that these pesticides impact the reproductive axis and we hypothesized that a dietary exposure would result in impaired reproduction. However, oocyte distribution, gonadosomatic index, plasma vitellogenin, and plasma sex steroids (17β-estradiol, E2 and testosterone, T) were not different between control animals and contaminant-fed largemouth bass. Moreover, neither p, p’ DDE nor MXC affected E2 or T production in ex vivo oocyte cultures from chemical-fed largemouth bass. However, both pesticides did interfere with the normal upregulation of androgen receptor that is observed in response to human chorionic gonadotropin in ex vivo cultures, an observation that may be related to their anti-androgenic properties. Transcriptomics profiling in the ovary revealed that gene networks related to cell processes such as leukocyte cell adhesion, ossification, platelet function and inhibition, xenobiotic metabolism, fibrinolysis, and thermoregulation were altered by p, p’ DDE, MXC, and flutamide. Interestingly, immune-related gene networks were suppressed by all three chemicals. The data suggest that p, p’ DDE and flutamide affected more genes in common with each other than either chemical with MXC, consistent with studies suggesting that p, p’ DDE is a more potent anti-androgen than MXC. These data demonstrate that reproductive health was not affected by these specific dietary treatments, but rather the immune system, which may be a significant target of organochlorine pesticides. The interaction between the reproductive and immune systems should be considered in future studies on these legacy and persistent pesticides.
Clinical Validation of R-T Estimation for CoaguChek XS INR Results.
Author information: Richter C1, Taylor J2, Wright J3, Fletcher B4.
1UF Health Shands Hospital, Gainesville, FL, USA richtc@shands.ufl.edu.
2University of Florida College of Pharmacy, Gainesville, FL, USA.
3UF Health Shands Hospital, Gainesville, FL, USA.
4University of Florida Department of Medicine, Gainesville, FL, USA.
Journal: The Annals of Pharmacotherapy
Date of e-pub: August 2016
Abstract:
BACKGROUND:
Despite the emergence of several new oral anticoagulants, warfarin remains a widely used form of anticoagulation that continues to have a role in the treatment of cardiac and thrombotic conditions.
OBJECTIVE:
The goal of this study was to evaluate whether the R-T estimation, an equation developed in a previous study, was a valid clinical tool in managing patients’ warfarin therapy in an anticoagulation clinic in lieu of obtaining a venipuncture international normalized ratio (INR) secondary to a high CoaguChek XS (CXS) INR.
METHODS:
This study used a randomized double-blind method to compare the clinical decisions made using venipuncture or CXS machine and recorded the INR, percentage dose change, time to clinical decision from check-in, and scheduled follow-up.
RESULTS:
In the analysis of the difference in percentage dose change, a 1.0% (95% CI = -0.78 to 2.68; P = 0.27) difference was observed overall, and a 1.2% (95% CI = -0.59 to 2.95; P = 0.18) difference was observed in the 4 to 5.9 subgroup. Clinical decisions were reached 17 minutes faster (95% CI = 11-24; P < 0.001) overall and 17 minutes faster (95% CI = 10-24; P < 0.001) in the 4 to 5.9 subgroup. Scheduled follow-up was 0.38 weeks sooner (95% CI = 0.01-0.67; P = 0.014) overall and 0.36 weeks sooner (95% CI = 0-0.66; P = 0.041) in the 4 to 5.9 subgroup.
CONCLUSIONS:
The results of this study support the use of the R-T estimation for correction of INR values obtained using the CXS meter when the INR is in the range of 4 to 5.9. This correction will allow clinics using this device to more efficiently manage patients taking warfarin.
Tetracycline-suppressible female lethality and sterility in the Mexican fruit fly, Anastrepha ludens.
Author information: Schetelig MF1,2, Targovska A3, Meza JS4, Bourtzis K3, Handler AM2.
1Justus-Liebig-University Giessen, Institute for Insect Biotechnology, Giessen, Germany.
2USDA/ARS, Center for Medical, Agricultural and Veterinary Entomology, Gainesville, FL, USA.
3Insect Pest Control Laboratory, Joint FAO/IAEA Programme of Nuclear Techniques in Food and Agriculture, Vienna, Austria.
4Programa Moscafrut, SAGARPA-IICA, Metapa de Dominguez, Chiapas, Mexico.
Journal: Insect Molecular Biology
Date of e-pub: August 2016
Abstract: The sterile insect technique (SIT) involves the mass release of sterile males to suppress insect pest populations. SIT has been improved for larval pests by the development of strains for female-specific tetracycline-suppressible (Tet-off) embryonic lethal systems for male-only populations. Here we describe the extension of this approach to the Mexican fruit fly, Anastrepha ludens, using a Tet-off driver construct with the Tet-transactivator (tTA) under embryo-specific Anastrepha suspensa serendipity α (As-sry-α) promoter regulation. In the absence of tetracycline, tTA acts upon a Tet-response element linked to the pro-apoptotic cell death gene lethal effector, head involuation defective (hid), from A. ludens (Alhid(Ala2) ) that contains a sex-specific intron splicing cassette, resulting in female-specific expression of the lethal effector. Parental adults double-homozygous for the driver/effector vectors were expected to yield male-only progeny when reared on Tet-free diet, but a complete lack of oviposited eggs resulted for each of the three strains tested. Ovary dissection revealed nonvitellogenic oocytes in all strains that was reversible by feeding females tetracycline for 5 days after eclosion, resulting in male-only adults in one strain. Presumably the sry-α promoter exhibits prezygotic maternal expression as well as zygotic embryonic expression in A. ludens, resulting in a Tet-off sterility effect in addition to female-specific lethality.
Metabolic regulation of triacylglycerol accumulation in the green algae: identification of potential targets for engineering to improve oil yield.
Author information: Goncalves EC1, Wilkie AC2, Kirst M3, Rathinasabapathi B1.
1Plant Molecular and Cellular Biology Program, Horticultural Sciences Department, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, USA.
2Soil and Water Science Department, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, USA.
3School of Forestry, University of Florida, Gainesville, FL, USA.
Journal: Plant Biotechnology Journal
Date of e-pub: August 2016
Abstract: The great need for more sustainable alternatives to fossil fuels has increased our research interests in algal biofuels. Microalgal cells, characterized by high photosynthetic efficiency and rapid cell division, are an excellent source of neutral lipids as potential fuel stocks. Various stress factors, especially nutrient-starvation conditions, induce an increased formation of lipid bodies filled with triacylglycerol in these cells. Here we review our knowledge base on glycerolipid synthesis in the green algae with an emphasis on recent studies on carbon flux, redistribution of lipids under nutrient-limiting conditions and its regulation. We discuss the contributions and limitations of classical and novel approaches used to elucidate the algal triacylglycerol biosynthetic pathway and its regulatory network in green algae. Also discussed are gaps in knowledge and suggestions for much needed research both on the biology of triacylglycerol accumulation and possible avenues to engineer improved algal strains.
NOTE: These abstracts were retrieved from the U.S. National Library of Medicine website managed in collaboration with the U.S. National Library of Medicine