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James West, W Warren Gill
Genome editing in large animals has tremendous practical applications, from more accurate models for medical research through improved animal welfare and production efficiency. Although genetic modification in large animals has a 30 year history, until recently technical issues limited its utility. The original methods - pronuclear injection and integrating viruses - were plagued with problems associated with low efficiency, silencing, poor regulation of gene expression, and variability associated with random integration...
June 2016: Journal of Equine Veterinary Science
Chun Ma, Violetta Karwacki-Neisius, Haoran Tang, Wenjing Li, Zhennan Shi, Haolin Hu, Wenqi Xu, Zhentian Wang, Lingchun Kong, Ruitu Lv, Zheng Fan, Wenhao Zhou, Pengyuan Yang, Feizhen Wu, Jianbo Diao, Li Tan, Yujiang Geno Shi, Fei Lan, Yang Shi
Nono is a component of the para-speckle, which stores and processes RNA. Mouse embryonic stem cells (mESCs) lack para-speckles, leaving the function of Nono in mESCs unclear. Here, we find that Nono functions as a chromatin regulator cooperating with Erk to regulate mESC pluripotency. We report that Nono loss results in robust self-renewing mESCs with epigenomic and transcriptomic features resembling the 2i (GSK and Erk inhibitors)-induced "ground state." Erk interacts with and is required for Nono localization to a subset of bivalent genes that have high levels of poised RNA polymerase...
October 18, 2016: Cell Reports
Katherine L Tully, Jonathan Hickman, Madeline McKenna, Christopher Neill, Cheryl A Palm
Fertilizer applications are poised to increase across sub-Saharan Africa (SSA), but the fate of added nitrogen (N) is largely unknown. We measured vertical distributions and temporal variations of soil inorganic N following fertilizer application in two maize (Zea mays L.)-growing regions of contrasting soil type. Fertilizer trials were established on a clayey soil in Yala, Kenya, and on a sandy soil in Tumbi, Tanzania, with application rates of 0-200 kg N/ha/yr. Soil profiles were collected (0-400 cm) annually (for three years in Yala and two years in Tumbi) to examine changes in inorganic N pools...
September 2016: Ecological Applications: a Publication of the Ecological Society of America
Steven Steinhubl
Despite having the basic tools necessary to appropriately identify and manage individuals with hypertension for over half a century it remains the single greatest contributing risk factor to morbidity and mortality worldwide today. Since diagnosis and effective treatment availability are not issues, this major failing in care can be attributed to inadequate systems of care: systems that have led to only <20% of hypertensive individuals globally having their blood pressure adequately controlled. Even in the US, where it is one of the most common reasons for a primary care visit, and with over $42...
September 2016: Journal of Hypertension
Siniša Urban
Rhomboid proteins are considered to be the most widespread membrane proteins across all forms of life. This superfamily comprises both active intramembrane serine proteases that catalyze the release of factors from the membrane, and a eukaryotic subset of non-catalytic members in which rhomboid architecture supports deviating functions. Although rhomboid was discovered in genetic studies of insect development, rhomboid research has broadened dramatically over the past 15 years; rhomboid enzymes are now the best biophysically understood of all intramembrane proteases, and are considered promising therapeutic targets for diseases ranging from parasitic infections to Parkinsonian neurodegeneration...
October 14, 2016: Seminars in Cell & Developmental Biology
Stefania Prendes-Alvarez, Charles B Nemeroff
Personalized or precision medicine is a medical discipline that proposes tailoring health care to each individual by integrating data from their genetic makeup, epigenetic modifications, other biomarkers, clinical symptoms and environmental exposures. Currently, patients typically present for treatment of mood disorders relatively late in the disease course and this is of great concern both because delay in attaining remission reduces the success of subsequent treatment and depressive episodes have negative cumulative effects on the brain and body...
October 13, 2016: Neuroscience Letters
Barbara Stetson, Karl E Minges, Caroline R Richardson
Accelerating diabetes rates have resulted in a global public health epidemic. Lifestyle change is a cornerstone of care, yet regimen demands may result in adherence difficulties. Distress, depression, and other psychosocial concerns are higher in those with diabetes. While interventions, such as the Diabetes Prevention Program appear to be effective, further research is needed to support the translation of interventions to prevent diabetes. Studies assessing optimal approaches to promoting effective decision making, coping and adherence are needed...
October 14, 2016: Journal of Behavioral Medicine
V Gohel, K Ranganathan, G Duan
Conventional grain ethanol manufacturing is a high temperature energy intensive process comprising of multiple unit operations when combined with lower ethanol recovery results in higher production cost. In liquefaction, jet cooking accounts for significant energy cost while strong acid or base used for pH adjustment presents a safety hazard. A need is felt for sustainable ethanol manufacturing process that is less hazardous, consumes lower energy and operates in a low pH range of 4.50 to 5.50. A Single Temperature Liquefaction (STL) process that could efficiently operate at lower liquefaction temperature over a pH range of 4...
October 13, 2016: Preparative Biochemistry & Biotechnology
Jennifer Fang, Kelley Lee, Nidhi Sejpal
The China National Tobacco Corporation (CNTC), which produces one-third of the world's cigarettes, is the largest tobacco company in the world. Over the past 60 years, the CNTC has been focused on supplying a huge domestic market. As the market has become increasingly saturated, and potential foreign competition looms, the company has turned to expansion abroad. This paper examines the ambitions and prospects of the CNTC to 'go global'. Using Chinese and English language sources, this paper describes the globalisation ambitions of the CNTC, and its global business strategy focused on internal restructuring, brand development and expansion of overseas operations in selected markets...
October 13, 2016: Global Public Health
Steven Jarrett, Theodor Dingermann
BACKGROUND: Pharmacists are the recognized experts in pharmacotherapy. With the recent introduction of biosimilar agents into the US market, pharmacists are poised to play a pivotal role in evaluating their risks versus benefits within the framework of cost containment. PURPOSE: This article provides hospital pharmacists with the necessary information on the principles surrounding the development, approval process, and use of biosimilars. METHODS: Information contained in this article enables hospital pharmacists to identify concerns relating to biosimilars, implement educational components, and successfully evaluate biosimilars for the addition to the formulary...
November 2015: Hospital Pharmacy
Sheryl Southard, Ju-Ryoung Kim, SiewHui Low, Richard W Tsika, Christoph Lepper
When unperturbed, somatic stem cells are poised to affect immediate tissue restoration upon trauma. Yet, little is known regarding the mechanistic basis controlling initial and homeostatic 'scaling' of stem cell pool sizes relative to their target tissues for effective regeneration. Here, we show that TEAD1-expressing skeletal muscle of transgenic mice features a dramatic hyperplasia of muscle stem cells (i.e. satellite cells, SCs) but surprisingly without affecting muscle tissue size. Super-numeral SCs attain a 'normal' quiescent state, accelerate regeneration, and maintain regenerative capacity over several injury-induced regeneration bouts...
October 11, 2016: ELife
Liam Wilbraham, François-Xavier Coudert, Ilaria Ciofini
Design of optical properties within metal-organic frameworks (MOFs) is a subject of ever increasing attention in recent years with theoretical approaches poised to play a key role alongside experiment in both the understanding of fundamental mechanisms and the further development of high performance materials. We have developed and applied a simple and computationally affordable protocol rooted in density functional theory (DFT) and its time dependent counterpart (TD-DFT) to two isostructural MOFs based on a 4,4'-bis((3,5-dimethyl-1H-pyrazol-4-yl)methyl)-biphenyl (H2DMPMB) linker...
September 14, 2016: Physical Chemistry Chemical Physics: PCCP
Mary Prahl, Prasanna Jagannathan, Tara I McIntyre, Ann Auma, Lila Farrington, Samuel Wamala, Mayimuna Nalubega, Kenneth Musinguzi, Kate Naluwu, Esther Sikyoma, Rachel Budker, Hilary Vance, Pamela Odorizzi, Patience Nayebare, John Ategeka, Abel Kakuru, Diane V Havlir, Moses R Kamya, Grant Dorsey, Margaret E Feeney
BACKGROUND: In malaria-endemic areas, the first exposure to malaria antigens often occurs in utero when the fetal immune system is poised towards the development of tolerance. Children exposed to placental malaria have an increased risk of clinical malaria in the first few years of life compared to unexposed children. Recent work has suggested the potential of pregnancy-associated malaria to induce immune tolerance in children living in malaria-endemic areas. A study was completed to evaluate the effect of malaria exposure during pregnancy on fetal immune tolerance and effector responses...
October 7, 2016: Malaria Journal
Cherie R Kagan, Laura E Fernandez, Yury Gogotsi, Paula T Hammond, Mark C Hersam, André E Nel, Reginald M Penner, C Grant Willson, Paul S Weiss
Nanoscience and nanotechnology are poised to contribute to a wide range of fields, from health and medicine to electronics, energy, security, and more. These contributions come both directly in the form of new materials, interfaces, tools, and even properties as well as indirectly by connecting fields together. We celebrate how far we have come, and here, we look at what is to come over the next decade that will leverage the strong and growing base that we have built in nanoscience and nanotechnology.
October 7, 2016: ACS Nano
Rubel Chakravarty, Sudipta Chakraborty, Ashutosh Dash
Positron emission tomography (PET) imaging has transformed diagnostic nuclear medicine and become an essential strategy in cancer management. With the expected growth of this molecular imaging modality, there is a recognized need for new PET probes to address the clinical challenges in the early diagnosis and staging of various types of cancers. In this endeavor, the prospect of using 64Cu in the form of simple Cu2+ ions as PET probe is not only a cost-effective proposition, but also seems poised to broaden the palette of molecular imaging probes in the foreseeable future...
October 6, 2016: Molecular Pharmaceutics
Carlos H Villa, Douglas B Cines, Don L Siegel, Vladimir Muzykantov
Red blood cells (RBCs) are innate carriers that can also be engineered to improve the pharmacokinetics and pharmacodynamics of many drugs, particularly biotherapeutics. Successful loading of drugs, both internally and on the external surface of RBCs, has been demonstrated for many drugs including anti-inflammatory, antimicrobial, and antithrombotic agents. Methods for internal loading of drugs within RBCs are now entering clinical use. Although internal loading can result in membrane disruption that may compromise biocompatibility, surface loading using either affinity or chemical ligands offers a diverse set of approaches for the production of RBC drug carriers...
August 17, 2016: Transfusion Medicine Reviews
Jean Frantz Lemoine, Anne Marie Desormeaux, Franck Monestime, Carl Renad Fayette, Luccene Desir, Abdel Nasser Direny, Sarah Carciunoiu, Lior Miller, Alaine Knipes, Patrick Lammie, Penelope Smith, Melissa Stockton, Lily Trofimovich, Kalpana Bhandari, Richard Reithinger, Kathryn Crowley, Eric Ottesen, Margaret Baker
Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA) program led by the Ministry of Public Health and Population and its collaborating international partners. By 2012, Haiti's neglected tropical disease (NTD) program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country. Essential to this success have been in the detail of how MDAs were implemented...
October 2016: PLoS Neglected Tropical Diseases
Sana A Shaikh, Drew M Dolino, Garam Lee, Sudeshna Chatterjee, David M MacLean, Charlotte Flatebo, Christy F Landes, Vasanthi Jayaraman
Fast excitatory synaptic signaling in the mammalian brain is mediated by AMPA-type ionotropic glutamate receptors. In neurons, AMPA receptors co-assemble with auxiliary proteins, such as stargazin, which can markedly alter receptor trafficking and gating. Here, we used luminescence resonance energy transfer measurements to map distances between the full-length, functional AMPA receptor and stargazin expressed in HEK293 cells and to determine the ensemble structural changes in the receptor due to stargazin. In addition, we used single-molecule fluorescence resonance energy transfer to study the structural and conformational distribution of the receptor and how this distribution is affected by stargazin...
October 4, 2016: Cell Reports
Shahana Mitra, Baijayanti Ghosh, Nilanjan Gayen, Joydeep Roy, Atin K Mandal
CRAF kinase maintains cell viability, growth and proliferation by participating in MAPK pathway. Unlike BRAF, CRAF requires continuous chaperoning by Hsp90 to retain MAPK signaling. But, the reason behind the continuous association of Hsp90 with CRAF is still elusive. In this study, we have identified the bipartite role of Hsp90 in chaperoning CRAF kinase. Hsp90 facilitates Ser-621 phosphorylation of CRAF and prevents the kinase from degradation. Co-chaperone Cdc37 assists in this phosphorylation event. However, after folding the stability of the kinase becomes insensitive to Hsp90 inhibition, although the physical association between Hsp90 and CRAF remains intact...
October 4, 2016: Journal of Biological Chemistry
Päivi L H Rinne, Laju K Paul, Jorma Vahala, Jaakko Kangasjärvi, Christiaan van der Schoot
Axillary buds (AXBs) of hybrid aspen (Populus tremula×P. tremuloides) contain a developing dwarfed shoot that becomes para-dormant at the bud maturation point. Para-dormant AXBs can grow out after stem decapitation, while dormant AXBs pre-require long-term chilling to release them from dormancy. The latter is mediated by gibberellin (GA)-regulated 1,3-β-glucanases, but it is unknown if GA is also important in the development, activation, and outgrowth of para-dormant AXBs. The present data show that para-dormant AXBs up-regulate GA receptor genes during their maturation, but curtail GA biosynthesis by down-regulating the rate-limiting GIBBERELLIN 3-OXIDASE2 (GA3ox2), which is characteristically expressed in the growing apex...
October 3, 2016: Journal of Experimental Botany
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