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https://www.readbyqxmd.com/read/28698577/the-evolutionary-advantage-of-heritable-phenotypic-heterogeneity
#1
Oana Carja, Joshua B Plotkin
Phenotypic plasticity is an evolutionary driving force in diverse biological processes, including the adaptive immune system, the development of neoplasms, and the persistence of pathogens despite drug pressure. It is essential, therefore, to understand the evolutionary advantage of an allele that confers on cells the ability to express a range of phenotypes. Here, we study the fate of a new mutation that allows the expression of multiple phenotypic states, introduced into a finite population of individuals that can express only a single phenotype...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28677690/vaccination-ecosystem-health-check-achieving-impact-today-and-sustainability-for-tomorrow
#2
Mitra Saadatian-Elahi, David Bloom, Stanley Plotkin, Valentina Picot, Jacques Louis, Michael Watson
BACKGROUND: Vaccination is a complex ecosystem with several components that interact with one another and with the environment. Today's vaccine ecosystem is defined by the pursuit of polio eradication, the drive to get as many of the new vaccines to as many people as possible and the research and development against immunologically challenging diseases. Despite these successes, vaccine ecosystem is facing keys issues with regard to supply/distribution and cost/profitability asymmetry that risk slowing its global growth...
2017: BMC Proceedings
https://www.readbyqxmd.com/read/28647887/connexins-and-pannexins-in-bone-and-skeletal-muscle
#3
REVIEW
Lilian I Plotkin, Hannah M Davis, Bruno A Cisterna, Juan C Sáez
PURPOSE OF REVIEW: To discuss current knowledge on the role of connexins and pannexins in the musculoskeletal system. RECENT FINDINGS: Connexins and pannexins are crucial for the development and maintenance of both bone and skeletal muscle. In bone, the presence of connexin and more recently of pannexin channels in osteoblasts, osteoclasts, and osteocytes has been described and shown to be essential for normal skeletal development and bone adaptation. In skeletal muscles, connexins and pannexins play important roles during development and regeneration through coordinated regulation of metabolic functions via cell-to-cell communication...
June 24, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28647170/the-complexity-and-cost-of-vaccine-manufacturing-an-overview
#4
REVIEW
Stanley Plotkin, James M Robinson, Gerard Cunningham, Robyn Iqbal, Shannon Larsen
As companies, countries, and governments consider investments in vaccine production for routine immunization and outbreak response, understanding the complexity and cost drivers associated with vaccine production will help to inform business decisions. Leading multinational corporations have good understanding of the complex manufacturing processes, high technological and R&D barriers to entry, and the costs associated with vaccine production. However, decision makers in developing countries, donors and investors may not be aware of the factors that continue to limit the number of new manufacturers and have caused attrition and consolidation among existing manufacturers...
June 21, 2017: Vaccine
https://www.readbyqxmd.com/read/28646957/whither-vaccines
#5
Charlene M C Rodrigues, Marta V Pinto, Manish Sadarangani, Stanley A Plotkin
Currently used vaccines have had major effects on eliminating common infections, largely by duplicating the immune responses induced by natural infections. Now vaccinology faces more complex problems, such as waning antibody, immunosenescence, evasion of immunity by the pathogen, deviation of immunity by the microbiome, induction of inhibitory responses, and complexity of the antigens required for protection. Fortunately, vaccine development is now incorporating knowledge from immunology, structural biology, systems biology and synthetic chemistry to meet these challenges...
June 2017: Journal of Infection
https://www.readbyqxmd.com/read/28644039/parkinson-s-disease-biomarkers-perspective-from-the-ninds-parkinson-s-disease-biomarkers-program
#6
Katrina Gwinn, Karen K David, Christine Swanson-Fischer, Roger Albin, Coryse St Hillaire-Clarke, Beth-Anne Sieber, Codrin Lungu, F DuBois Bowman, Roy N Alcalay, Debra Babcock, Ted M Dawson, Richard B Dewey, Tatiana Foroud, Dwight German, Xuemei Huang, Vlad Petyuk, Judith A Potashkin, Rachel Saunders-Pullman, Margaret Sutherland, David R Walt, Andrew B West, Jing Zhang, Alice Chen-Plotkin, Clemens R Scherzer, David E Vaillancourt, Liana S Rosenthal
Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development...
June 23, 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/28637206/improving-combination-osteoporosis-therapy-in-a-preclinical-model-of-heightened-osteoanabolism
#7
Yu Shao, Selene Hernandez-Buquer, Paul Childress, Keith R Stayrook, Marta B Alvarez, Hannah Davis, Lilian Plotkin, Yongzheng He, Keith W Condon, David B Burr, Stuart J Warden, Alexander G Robling, Feng-Chun Yang, Ronald C Wek, Matthew R Allen, Joseph P Bidwell
Combining anti-catabolic agents with parathyroid hormone (PTH) to enhance bone mass has yielded mixed results in osteoporosis patients. Towards the goal of enhancing the efficacy of these regimens, we tested their utility in combination with loss of the transcription factor Nmp4 since disabling this gene amplifies PTH-induced increases in trabecular bone in mice by boosting osteoblast secretory activity. We addressed whether combining a sustained anabolic response with an anti-catabolic results in superior bone acquisition compared to PTH mono-therapy...
June 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/28629863/the-unfolding-mechanism-of-monomeric-mutant-sod1-by-simulated-force-spectroscopy
#8
Mona Habibi, Jörg Rottler, Steven S Plotkin
Mechanical unfolding of mutated apo, disulfide-reduced, monomeric superoxide dismutase 1 protein (SOD1) has been simulated via force spectroscopy techniques, using both an all-atom (AA), explicit solvent model and a coarse-grained heavy-atom Gō (HA-Gō) model. The HA-Gō model was implemented at two different pulling speeds for comparison. The most-common sequence of unfolding in the AA model agrees well with the most-common unfolding sequence of the HA-Gō model, when the same normalized pulling rate was used...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28610977/novel-3-fluoro-6-methoxyquinoline-derivatives-as-inhibitors-of-bacterial-dna-gyrase-and-topoisomerase-iv
#9
Mark J Mitton-Fry, Steven J Brickner, Judith C Hamel, Rose Barham, Lori Brennan, Jeffrey M Casavant, Xiaoyuan Ding, Steven Finegan, Joel Hardink, Thuy Hoang, Michael D Huband, Meghan Maloney, Anthony Marfat, Sandra P McCurdy, Dale McLeod, Chakrapani Subramanyam, Michael Plotkin, Usa Reilly, John Schafer, Gregory G Stone, Daniel P Uccello, Todd Wisialowski, Kwansik Yoon, Richard Zaniewski, Christopher Zook
Novel (non-fluoroquinolone) inhibitors of bacterial type II topoisomerases (NBTIs) are an emerging class of antibacterial agents. We report an optimized series of cyclobutylaryl-substituted NBTIs. Compound 14 demonstrated excellent activity both in vitro (S. aureus MIC90=0.125μg/mL) and in vivo (systemic and tissue infections). Enhanced inhibition of Topoisomerase IV correlated with improved activity in S. aureus strains with mutations conferring resistance to NBTIs. Compound 14 also displayed an improved hERG IC50 of 85...
August 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28592453/diagnosis-and-management-of-dementia-with-lewy-bodies-fourth-consensus-report-of-the-dlb-consortium
#10
REVIEW
Ian G McKeith, Bradley F Boeve, Dennis W Dickson, Glenda Halliday, John-Paul Taylor, Daniel Weintraub, Dag Aarsland, James Galvin, Johannes Attems, Clive G Ballard, Ashley Bayston, Thomas G Beach, Frédéric Blanc, Nicolaas Bohnen, Laura Bonanni, Jose Bras, Patrik Brundin, David Burn, Alice Chen-Plotkin, John E Duda, Omar El-Agnaf, Howard Feldman, Tanis J Ferman, Dominic Ffytche, Hiroshige Fujishiro, Douglas Galasko, Jennifer G Goldman, Stephen N Gomperts, Neill R Graff-Radford, Lawrence S Honig, Alex Iranzo, Kejal Kantarci, Daniel Kaufer, Walter Kukull, Virginia M Y Lee, James B Leverenz, Simon Lewis, Carol Lippa, Angela Lunde, Mario Masellis, Eliezer Masliah, Pamela McLean, Brit Mollenhauer, Thomas J Montine, Emilio Moreno, Etsuro Mori, Melissa Murray, John T O'Brien, Sotoshi Orimo, Ronald B Postuma, Shankar Ramaswamy, Owen A Ross, David P Salmon, Andrew Singleton, Angela Taylor, Alan Thomas, Pietro Tiraboschi, Jon B Toledo, John Q Trojanowski, Debby Tsuang, Zuzana Walker, Masahito Yamada, Kenji Kosaka
The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and (123)iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy...
July 4, 2017: Neurology
https://www.readbyqxmd.com/read/28574876/utility-of-follow-up-dopamine-transporter-spect-with-123i-fp-cit-in-the-diagnostic-workup-of-patients-with-clinically-uncertain-parkinsonian-syndrome
#11
Ivayla Apostolova, Daulat S Taleb, Axel Lipp, Imke Galazky, Dennis Kupitz, Catharina Lange, Marcus R Makowski, Winfried Brenner, Holger Amthauer, Michail Plotkin, Ralph Buchert
PURPOSE: Dopamine transporter SPECT with I-FP-CIT is registered for detection (or exclusion) of nigrostriatal degeneration to support the etiologic classification of parkinsonian syndromes. In case of uncertainty in the interpretation of SPECT findings or unexpected clinical course, follow-up SPECT might be useful. However, the utility of follow-up FP-CIT SPECT has not yet been clarified. METHODS: One hundred forty-one patients (65.1 ± 10.4 years) from 3 sites with follow-up FP-CIT SPECT 22...
August 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28567317/open-label-fosmetpantotenate-a-phosphopantothenate-replacement-therapy-in-a-single-patient-with-atypical-pkan
#12
Yiolanda-Panayiota Christou, George A Tanteles, Elena Kkolou, Annita Ormiston, Kostas Konstantopoulos, Maria Beconi, Randall D Marshall, Horacio Plotkin, Kleopas A Kleopa
Objective. Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder with variable onset, rate of progression, and phenotypic expression. Later-onset, more slowly progressive PKAN often presents with neuropsychiatric as well as motor manifestations that include speech difficulties, progressive dystonia, rigidity, and parkinsonism. PKAN is caused by biallelic PANK2 mutations, a gene that encodes pantothenate kinase 2, a regulatory enzyme in coenzyme A biosynthesis. Current therapeutic strategies rely on symptomatic relief...
2017: Case Reports in Neurological Medicine
https://www.readbyqxmd.com/read/28542444/regional-brain-amyloid-%C3%AE-accumulation-associates-with-domain-specific-cognitive-performance-in-parkinson-disease-without-dementia
#13
Rizwan S Akhtar, Sharon X Xie, Yin J Chen, Jacqueline Rick, Rachel G Gross, Ilya M Nasrallah, Vivianna M Van Deerlin, John Q Trojanowski, Alice S Chen-Plotkin, Howard I Hurtig, Andrew D Siderowf, Jacob G Dubroff, Daniel Weintraub
Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients...
2017: PloS One
https://www.readbyqxmd.com/read/28529307/genetic-deletion-of-sost-or-pharmacological-inhibition-of-sclerostin-prevent-multiple-myeloma-induced-bone-disease-without-affecting-tumor-growth
#14
J Delgado-Calle, J Anderson, M D Cregor, K W Condon, S A Kuhstoss, L I Plotkin, T Bellido, G D Roodman
Multiple myeloma (MM) causes lytic bone lesions due to increased bone resorption and concomitant marked suppression of bone formation. Sclerostin (Scl), an osteocyte-derived inhibitor of Wnt/β-catenin signaling, is elevated in MM patient sera and increased in osteocytes in MM-bearing mice. We show here that genetic deletion of Sost, the gene encoding Scl, prevented MM-induced bone disease in an immune-deficient mouse model of early MM, and that administration of anti-Scl antibody (Scl-Ab) increased bone mass and decreases osteolysis in immune-competent mice with established MM...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28515856/inter-ethnic-marriages-and-severity-of-coronary-artery-disease-a-multicenter-study-of-arabian-gulf-states
#15
Amin Daoulah, Salem Al-Kaabi, Amir Lotfi, Mushabab Al-Murayeh, S Ali Nasseri, Waleed Ahmed, Salah N Al-Otaibi, Mohamed N Alama, Osama E Elkhateeb, Amy J Plotkin, Majed M Malak, Khalid Alshali, Mohamed Hamzi, Saleh Al Khunein, Mohammed Abufayyah, Alawi A Alsheikh-Ali
AIM: To assess the association of inter-ethnic vs intra-ethnic marriage with severity of coronary artery disease (CAD) in men undergoing angiography. METHODS: We conducted a prospective multicenter, multi-ethnic, cross sectional observational study at five hospitals in Saudi Arabia and the United Arab Emirates, in which we used logistic regression analysis with and without adjustment for baseline differences. RESULTS: Data were collected for 1068 enrolled patients undergoing coronary angiography for clinical indications during the period of April 1(st), 2013 to March 30(th), 2014...
April 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28504192/correlates-of-protection-for-enteric-vaccines
#16
Jan Holmgren, Umesh D Parashar, Stanley Plotkin, Jacques Louis, Su-Peing Ng, Eric Desauziers, Valentina Picot, Mitra Saadatian-Elahi
An immunological Correlate of Protection (CoP) is an immune response that is statistically interrelated with protection. Identification of CoPs for enteric vaccines would help design studies to improve vaccine performance of licensed vaccines in low income settings, and would facilitate the testing of future vaccines in development that might be more affordable. CoPs are lacking today for most existing and investigational enteric vaccines. In order to share the latest information on CoPs for enteric vaccines and to discuss novel approaches to correlate mucosal immune responses in humans with protection, the Foundation Mérieux organized an international conference of experts where potential CoPs for vaccines were examined using case-studies for both bacterial and viral enteric pathogens...
May 11, 2017: Vaccine
https://www.readbyqxmd.com/read/28490424/waning-immunity-and-microbial-vaccines-workshop-of-the-national-institute-of-allergy-and-infectious-diseases
#17
Xin-Xing Gu, Stanley A Plotkin, Kathryn M Edwards, Alessandro Sette, Kingston H G Mills, Ofer Levy, Andrea J Sant, Annie Mo, William Alexander, Kristina T Lu, Christopher E Taylor
Since the middle of the 20th century, vaccines have made a significant public health impact by controlling infectious diseases globally. Although long-term protection has been achieved with some vaccines, immunity wanes over time with others, resulting in outbreaks or epidemics of infectious diseases. Long-term protection against infectious agents that have a complex life cycle and antigenic variation remains a key challenge. Novel strategies to characterize the short- and long-term immune responses to vaccines and to induce immune responses that mimic natural infection have recently emerged...
July 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28475707/infectious-disease-specialists-practice-what-you-preach
#18
Stanley Plotkin
No abstract text is available yet for this article.
May 5, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28457935/nf-%C3%AE%C2%BAb-inhibitors-that-prevent-foam-cell-formation-and-atherosclerotic-plaque-accumulation
#19
Jesse D Plotkin, Michael G Elias, Anthony L Dellinger, Christopher L Kepley
The transformation of monocyte-derived macrophages into lipid-laden foam cells is one inflammatory process underlying atherosclerotic disease. Previous studies have demonstrated that fullerene derivatives (FDs) have inflammation-blunting properties. Thus, it was hypothesized that FD could inhibit the transformation process underlying foam cell formation. Fullerene derivatives inhibited the phorbol myristic acid/oxidized low-density lipoprotein-induced differentiation of macrophages into foam cells as determined by lipid staining and morphology...
April 27, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28387684/neuropsychological-subgroups-in-non-demented-parkinson-s-disease-a-latent-class-analysis
#20
Laura Brennan, Kathryn M Devlin, Sharon X Xie, Dawn Mechanic-Hamilton, Baochan Tran, Howard H Hurtig, Alice Chen-Plotkin, Lama M Chahine, James F Morley, John E Duda, David R Roalf, Nabila Dahodwala, Jacqueline Rick, John Q Trojanowski, Paul J Moberg, Daniel Weintraub
BACKGROUND: Methods to detect early cognitive decline and account for heterogeneity of deficits in Parkinson's disease (PD) are needed. Quantitative methods such as latent class analysis (LCA) offer an objective approach to delineate discrete phenotypes of impairment. OBJECTIVE: To identify discrete neurocognitive phenotypes in PD patients without dementia. METHODS: LCA was applied to a battery of 8 neuropsychological measures to identify cognitive subtypes in a cohort of 199 non-demented PD patients...
2017: Journal of Parkinson's Disease
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