231 research outputs found
Identification of regions in multiple sequence alignments thermodynamically suitable for targeting by consensus oligonucleotides: application to HIV genome
BACKGROUND: Computer programs for the generation of multiple sequence alignments such as "Clustal W" allow detection of regions that are most conserved among many sequence variants. However, even for regions that are equally conserved, their potential utility as hybridization targets varies. Mismatches in sequence variants are more disruptive in some duplexes than in others. Additionally, the propensity for self-interactions amongst oligonucleotides targeting conserved regions differs and the structure of target regions themselves can also influence hybridization efficiency. There is a need to develop software that will employ thermodynamic selection criteria for finding optimal hybridization targets in related sequences. RESULTS: A new scheme and new software for optimal detection of oligonucleotide hybridization targets common to families of aligned sequences is suggested and applied to aligned sequence variants of the complete HIV-1 genome. The scheme employs sequential filtering procedures with experimentally determined thermodynamic cut off points: 1) creation of a consensus sequence of RNA or DNA from aligned sequence variants with specification of the lengths of fragments to be used as oligonucleotide targets in the analyses; 2) selection of DNA oligonucleotides that have pairing potential, greater than a defined threshold, with all variants of aligned RNA sequences; 3) elimination of DNA oligonucleotides that have self-pairing potentials for intra- and inter-molecular interactions greater than defined thresholds. This scheme has been applied to the HIV-1 genome with experimentally determined thermodynamic cut off points. Theoretically optimal RNA target regions for consensus oligonucleotides were found. They can be further used for improvement of oligo-probe based HIV detection techniques. CONCLUSIONS: A selection scheme with thermodynamic thresholds and software is presented in this study. The package can be used for any purpose where there is a need to design optimal consensus oligonucleotides capable of interacting efficiently with hybridization targets common to families of aligned RNA or DNA sequences. Our thermodynamic approach can be helpful in designing consensus oligonucleotides with consistently high affinity to target variants in evolutionary related genes or genomes
The Lantern Vol. 47, No. 2, May 1981
• Festival • Ode to Old Tom • Living Room • Writing a Poem • Mission Impossible • The Hinge is Oiled • The Potter\u27s Field at Malvern • Points of Time • Attempted Autonomy • My Love • Love, not War • Death Comes Quickly • You Can\u27t Always Get What You Don\u27t Really Want • You See (Johnny\u27s Tale): An Elegy • Sanguine Hopeshttps://digitalcommons.ursinus.edu/lantern/1118/thumbnail.jp
2018 American Heart Association Focused Update on Pediatric Advanced Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
This 2018 American Heart Association focused update on pediatric advanced life support guidelines for cardiopulmonary resuscitation and emergency cardiovascular care follows the 2018 evidence review performed by the Pediatric Task Force of the International Liaison Committee on Resuscitation. It aligns with the International Liaison Committee on Resuscitation's continuous evidence review process, and updates are published when the group completes a literature review based on new published evidence. This update provides the evidence review and treatment recommendation for antiarrhythmic drug therapy in pediatric shock-refractory ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. As was the case in the pediatric advanced life support section of the "2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care," only 1 pediatric study was identified. This study reported a statistically significant improvement in return of spontaneous circulation when lidocaine administration was compared with amiodarone for pediatric ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. However, no difference in survival to hospital discharge was observed among patients who received amiodarone, lidocaine, or no antiarrhythmic medication. The writing group reaffirmed the 2015 pediatric advanced life support guideline recommendation that either lidocaine or amiodarone may be used to treat pediatric patients with shock-refractory ventricular fibrillation or pulseless ventricular tachycardia
Part 4: Pediatric basic and advanced life support 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care
Part 4: Pediatric basic and advanced life support 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care
More than 20 000 infants and children have a cardiac arrest per year in the United States. In 2015, emergency medical service–documented out-of-hospital cardiac arrest (OHCA) occurred in more than 7000 infants and children
New targets for therapy in breast cancer: Mammalian target of rapamycin (mTOR) antagonists
Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biologic functions such as transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In breast cancer this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. There is evidence suggesting that Akt promotes breast cancer cell survival and resistance to chemotherapy, trastuzumab, and tamoxifen. Rapamycin is a specific mTOR antagonist that targets this pathway and blocks the downstream signaling elements, resulting in cell cycle arrest in the G(1 )phase. Targeting the Akt/PI3K pathway with mTOR antagonists may increase the therapeutic efficacy of breast cancer therapy
Genetic variants for head size share genes and pathways with cancer
The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.</p
What Do Men Want from a Health Screening Mobile App? A Qualitative Study.
There is a lack of mobile app which aims to improve health screening uptake developed for men. As part of the study to develop an effective mobile app to increase health screening uptake in men, we conducted a needs assessment to find out what do men want from a health screening mobile app. In-depth interviews and focus group discussions were conducted with 31 men from a banking institution in Kuala Lumpur. The participants were purposely sampled according to their job position, age, ethnicity and screening status. The recruitment was stopped once data saturation was achieved. The audio-recorded interviews were transcribed verbatim and analyzed using thematic approach. Three themes emerged from the analysis and they were: content, feature and dissemination. In terms of the content, men wanted the app to provide information regarding health screening and functions that can assess their health; which must be personalized to them and are trustable. The app must have user-friendly features in terms of information delivery, ease of use, attention allocation and social connectivity. For dissemination, men proposed that advertisements, recommendations by health professionals, providing incentive and integrating the app as into existing systems may help to increase the dissemination of the app. This study identified important factors that need to be considered when developing a mobile app to improve health screening uptake. Future studies on mobile app development should elicit users' preference and need in terms of its content, features and dissemination strategies to improve the acceptability and the chance of successful implementation
Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy
The mammalian target of rapamycin (mTOR) is an intracellular serine/threonine protein kinase positioned at a central point in a variety of cellular signaling cascades. The established involvement of mTOR activity in the cellular processes that contribute to the development and progression of cancer has identified mTOR as a major link in tumorigenesis. Consequently, inhibitors of mTOR, including temsirolimus, everolimus, and ridaforolimus (formerly deforolimus) have been developed and assessed for their safety and efficacy in patients with cancer. Temsirolimus is an intravenously administered agent approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for the treatment of advanced renal cell carcinoma (RCC). Everolimus is an oral agent that has recently obtained US FDA and EMEA approval for the treatment of advanced RCC after failure of treatment with sunitinib or sorafenib. Ridaforolimus is not yet approved for any indication. The use of mTOR inhibitors, either alone or in combination with other anticancer agents, has the potential to provide anticancer activity in numerous tumor types. Cancer types in which these agents are under evaluation include neuroendocrine tumors, breast cancer, leukemia, lymphoma, hepatocellular carcinoma, gastric cancer, pancreatic cancer, sarcoma, endometrial cancer, and non-small-cell lung cancer. The results of ongoing clinical trials with mTOR inhibitors, as single agents and in combination regimens, will better define their activity in cancer
Immunological Change in a Parasite-Impoverished Environment: Divergent Signals from Four Island Taxa
Dramatic declines of native Hawaiian avifauna due to the human-mediated emergence of avian malaria and pox prompted an examination of whether island taxa share a common altered immunological signature, potentially driven by reduced genetic diversity and reduced exposure to parasites. We tested this hypothesis by characterizing parasite prevalence, genetic diversity and three measures of immune response in two recently-introduced species (Neochmia temporalis and Zosterops lateralis) and two island endemics (Acrocephalus aequinoctialis and A. rimitarae) and then comparing the results to those observed in closely-related mainland counterparts. The prevalence of blood parasites was significantly lower in 3 of 4 island taxa, due in part to the absence of certain parasite lineages represented in mainland populations. Indices of genetic diversity were unchanged in the island population of N. temporalis; however, allelic richness was significantly lower in the island population of Z. lateralis while both allelic richness and heterozygosity were significantly reduced in the two island-endemic species examined. Although parasite prevalence and genetic diversity generally conformed to expectations for an island system, we did not find evidence for a pattern of uniformly altered immune responses in island taxa, even amongst endemic taxa with the longest residence times. The island population of Z. lateralis exhibited a significantly reduced inflammatory cell-mediated response while levels of natural antibodies remained unchanged for this and the other recently introduced island taxon. In contrast, the island endemic A. rimitarae exhibited a significantly increased inflammatory response as well as higher levels of natural antibodies and complement. These measures were unchanged or lower in A. aequinoctialis. We suggest that small differences in the pathogenic landscape and the stochastic history of mutation and genetic drift are likely to be important in shaping the unique immunological profiles of small isolated populations. Consequently, predicting the impact of introduced disease on the many other endemic faunas of the remote Pacific will remain a challenge
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