Syracuse, NY, United States

SUNY Upstate Medical University
Syracuse, NY, United States

The State University of New York Upstate Medical University is a SUNY health science university located primarily in the University Hill district of Syracuse, New York. SUNY Upstate is an upper-division transfer and graduate college with degree programs within the College of Medicine, College of Nursing, College of Health Professions, and the College of Graduate Studies. Its Syracuse campus includes Upstate University Hospital.In addition to affiliations with Binghamton Hospital and 22 other hospitals throughout central New York, where much of the core clinical teaching takes place, Upstate has numerous partnerships, including a joint Ph.D. Program in Biomedical Engineering with Syracuse University; science enrichment programs for local youth in tandem with the SC Hope Clinic; and SUNY-ESF.It directly generates 8,195 jobs, making it Central New York's largest employer. Wikipedia.

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TAMPA, Fla. (May 9, 2017) -- Transmission of mosquito-borne diseases, such as Zika, occur at lower temperatures than previously thought, a recently released study co-authored by two University of South Florida researchers shows. The study, led by Stanford University and published in the journal PLoS Neglected Tropical Diseases, found that transmission of dengue, chikungunya and Zika is highest at around 84 degrees Fahrenheit. Scientists had long considered 90 degrees to be the peak-transmission temperature. The finding is significant, especially as climate change causes temperatures to climb. "This means that future transmission is much more likely to occur in subtropical and even temperate areas, such as the southern United States and northern Mexico," said Jeremy Cohen, PhD, a postdoctoral researcher studying integrative biology. He and Jason Rohr, PhD, an associate professor of integrative biology, are coauthors on the study. From 2015-2016, they collected data on the incidences of dengue, chikungunya and Zika, as well as climate, gross domestic product and tourism, in Latin America and the Caribbean. Their data were used to create a model that shows the potential effects of temperatures and temperature change on the transmission of dengue, chikungunya and Zika around the world, three diseases that are mosquito-vectored and increasing in the United States. "Our findings should help to predict the areas at the greatest risk of dengue, chikungunya and Zika outbreaks," said Rohr. Temperature affects how often mosquitoes bite, the amount of time it takes for them to ingest a virus from one human and inject it into another, and their life cycle. Cohen, Rohr and other members of the research team found that mosquitos posed the greatest risk to humans at 84 degrees and risk declined in cooler and warmer temperatures. "Given that the predominant thinking was that transmission was most likely to peak at very hot temperatures, which would mostly limit the diseases to the tropics, we were certainly surprised that the model and the field data suggested that high rates of transmission could occur at lower temperatures, possibly impacting more northern regions in the future," Cohen said. Pinpointing the optimal temperature for disease transmission is critical for predicting future disease rates and how diseases will spread with climate change, and more effectively implementing mosquito-control measures, said lead author Erin Mordecai of Stanford University. "If we're predicting a 29-degree optimum and another model is predicting a 35-degree optimum, the other model will say that climate change will increase transmission," she said in a Stanford-issued media release, adding that if local temperatures are already near optimal temperature, infections may decline as temperatures rise. In addition to USF and Stanford, researchers on the study represented institutions including Virginia Tech, University of Florida, University of Georgia College of Veterinary Medicine, University of California Los Angeles, SUNY Upstate Medical University, Penn State University and University of Michigan. The study was funded by a grant from the National Science Foundation -- Ecology and Evolution of Infectious Disease.

Personal DNA sequencing once promised to up the ante for individualized medicine. Perhaps no one believed that more than human genomics pioneer J. Craig Venter, who in 2014 co-founded a company called Human Longevity to predict and prevent disease by sequencing a million human genomes. But Venter is no longer content with your DNA. His latest venture—a subsidiary called Health Nucleus based in San Diego, California—says it can detect undiagnosed health problems by combining DNA analyses with a $25,000 workup including a whole-body MRI scan, metabolomics screening, 2 weeks of constant heart monitoring, pedigree analysis, microbiome sequencing, and a glut of standard laboratory tests. Enthusiasts of “precision medicine” say this kind of screening—similar to the U.S. National Institutes of Health’s (NIH’s) Precision Medicine Initiative—is the way of the future. But many other clinicians and researchers are leery or even downright outraged by the program’s potential for over diagnosis and what they see as lack of evidence for its benefits. Late last week, Venter and co-workers quietly published a paper on the preprint server bioRxiv—which does not use peer review—that appears to present data from the new project. According to the study, screening detected “age-related chronic diseases requiring prompt (<30 days) medical attention” in 8 % of the 209 participants, and MRIs found early-stage cancer in 2%. However, Health Nucleus did not confirm that the data were from its $25,000 medical exam, although descriptions of the diagnostics were nearly identical. “It’s a classic Craig Venter study that pushes the envelope of what is considered reasonable,” says Olivier Elemento, associate director at the Institute for Computational Biomedicine at Weill Cornell Medicine in Ithaca, New York. Meanwhile, Venter has been making the media rounds to promote the screening. On Fox Business, he said the exam finds “something seriously wrong” in 40% of participants (though that claim is left unexplained). CBS News reports that Venter’s group can predict Alzheimer’s disease 20 years in advance by scanning the 20 regions of the brain. And STAT news reports that the exams detect tumors early enough that every participant with cancer so far has been able to treat it, even the notoriously unforgiving pancreatic cancer. A spokesperson for Human Longevity said they would not comment on the contents of the paper until it is published in a peer-reviewed journal. Critics aren’t buying it. “If I wanted to write a Swiftian parody illustrating the insanity of this extreme version of [precision medicine], I could not have written a better paper,” says Nigel Paneth, a pediatrician and epidemiologist from Michigan State University in East Lansing, who cites a litany of problems that could result from the study including psychological damage, high medical costs, unnecessary tests, and “the absence of the slightest shred of evidence that any benefit will accrue to anyone.” Eric Topol, director of Scripps Translational Science Institute in San Diego says this is “kind of the most extensive diagnostic evaluation of people that has ever been done,” but he takes issue with billing the study as a precision medicine screening. “Is this precise or is this promiscuous?” he asks. “That term ‘precision medicine screening’ is very difficult to accept unless you prove that you are actually helping people. That hypothesis is still unproven after this paper was published,” Topol says. “What if it helps one and harms 10?” He’s particularly concerned  about running tests on people without a sound rationale. “Don’t do a bunch of tests unless there is a good reason; otherwise you get a bunch of false positives.” The study included twice as many men as women, and participants ranged in age from 20 to 98, with an average age of 55. A whopping 78% had “evidence of age-related chronic disease or risk factors,” which for the majority translated to diabetes or risk of atherosclerotic disease. Michael Joyner, a medical doctor and integrative physiology researcher at the Mayo Clinic in Rochester, Minnesota, also notes that over 70% of the participants are currently taking prescribed medication for high LDL cholesterol and hypertension. “To tell me that a bunch of 60-year-old men with prolonged EKG monitoring had some funny heartbeats … is news, give me a break,” he says. “The whole thing is an example of technology run amok from a belief that if you can measure it, it must be meaningful.” But the amped up testing has its proponents. “The over-diagnosis concern is completely over-exaggerated,” says Michael Snyder, the director of the Stanford Center for Genomics and Personalized Medicine in Palo Alto, California, who made news 5 years ago when he detected his own diabetes by intensively studying his body. “Some of the stuff they found seems pretty serious, so I think it is a good thing to catch that early,” he says, predicting that in the future, “we will be measuring thousands of things much more routinely.” Despite Venter’s personalized genomics evangelism, the study’s results pointedly indicate that “the genome alone doesn’t tell you the whole story,” says Elemento of Cornell. Only 25% of patients had probable links between gene variants and disease phenotypes. “But when you can combine genes with an additional readout that tells you the gene is doing something, your ability to predict disease increases dramatically.” Some see the early data from Health Nucleus as the potential start of another Venter-versus-the government scenario. “What Venter has done here is pretty much the goal of NIH’s Precision Medicine Initiative, and I imagine Craig envisions immediate scale-up to compete with that particular government project,” says Robert W. West Jr., who previously taught a course on precision medicine at SUNY Upstate Medical University. “If this is really Craig’s goal, then he would likely beat NIH to the punch again.” Health Nucleus says 570 people have participated in the full $25,000 panoramic medical workups thus far, but this week they launched a $7500 pared-down version that focuses on the full genome sequencing and full-body scan. “This is a study that is going to remain controversial,” Topol says. “And maybe it is futuristic, but I think most people in medicine who understand the history of this will know that this is potentially engendering trouble and doing all sorts of tests that don’t have any basis.”

Cingolani G.,Thomas Jefferson University | Duncan T.M.,SUNY Upstate Medical University
Nature Structural and Molecular Biology | Year: 2011

ATP synthase is a membrane-bound rotary motor enzyme that is critical for cellular energy metabolism in all kingdoms of life. Despite conservation of its basic structure and function, autoinhibition by one of its rotary stalk subunits occurs in bacteria and chloroplasts but not in mitochondria. The crystal structure of the ATP synthase catalytic complex (F 1) from Escherichia coli described here reveals the structural basis for this inhibition. The C-terminal domain of subunit adopts a heretofore unknown, highly extended conformation that inserts deeply into the central cavity of the enzyme and engages both rotor and stator subunits in extensive contacts that are incompatible with functional rotation. As a result, the three catalytic subunits are stabilized in a set of conformations and rotational positions distinct from previous F 1 structures. © 2011 Nature America, Inc. All rights reserved.

Cosgrove M.S.,SUNY Upstate Medical University
Nature Structural and Molecular Biology | Year: 2012

The application of time-resolved NMR spectroscopy to histone phosphorylation dynamics reveals mechanistic hierarchies within the active sites of the enzymes that regulate chromatin, thereby shedding new light on the complexity of the histone code. © 2012 Nature America, Inc. All rights reserved.

Kane P.M.,SUNY Upstate Medical University
Current Protein and Peptide Science | Year: 2012

Vacuolar proton-translocating ATPases (V-ATPases) are highly conserved proton pumps consisting of a peripheral membrane subcomplex called V1, which contains the sites of ATP hydrolysis, attached to an integral membrane subcomplex called Vo, which encompasses the proton pore. V-ATPase regulation by reversible dissociation, characterized by release of assembled V1 sectors into the cytosol and inhibition of both ATPase and proton transport activities, was first identified in tobacco hornworm and yeast. It has since become clear that modulation of V-ATPase assembly level is also a regulatory mechanism in mammalian cells. In this review, the implications of reversible disassembly for V-ATPase structure are discussed, along with insights into underlying subunit-subunit interactions provided by recent structural work. Although initial experiments focused on glucose deprivation as a trigger for disassembly, it is now clear that V-ATPase assembly can be regulated by other extracellular conditions. Consistent with a complex, integrated response to extracellular signals, a number of different regulatory proteins, including RAVE/rabconnectin, aldolase and other glycolytic enzymes, and protein kinase A have been suggested to control V-ATPase assembly and disassembly. It is likely that multiple signaling pathways dictate the ultimate level of assembly and activity. Tissue-specific V-ATPase inhibition is a potential therapy for osteoporosis and cancer; the possibility of exploiting reversible disassembly in design of novel V-ATPase inhibitors is discussed. © 2012 Bentham Science Publishers.

Imdad A.,SUNY Upstate Medical University
The Cochrane database of systematic reviews | Year: 2013

The umbilical cord is a structure made of blood vessels and connective tissue that connects the baby and placenta in utero. The umbilical cord is cut after birth, which separates the mother and her baby both physically and symbolically. Omphalitis is defined as infection of the umbilical cord stump. Tracking of bacteria along the umbilical vessels may lead to septicaemia that can result in neonatal morbidity and mortality, especially in developing countries. To determine the effect of application of antimicrobials on newborn's umbilical cord versus routine care for prevention of morbidity and mortality in hospital and community settings. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 October 2012). In addition, we also searched LILACS (1982 to 11 October 2012) and HERDIN NeON (October 2012) We included randomized, cluster-randomized and quasi-randomized controlled trials of topical cord care compared with no topical care, and comparisons between different forms of care. Two review authors independently assessed trials for inclusion, trial quality and subsequently extracted data. Data were checked for accuracy. The search identified 77 trials. We included 34 trials in the review involving 69,338 babies, five studies are awaiting classification and there are two ongoing community trials. Included studies were conducted in both developed and developing countries. Among the 34 included trials, three were large, cluster-randomized trials conducted in community settings in developing countries and 31 studies were conducted in hospital settings mostly in developed countries. Data for community and hospital studies were analyzed separately. The three trials conducted in community settings contributed 78% of the total number of children included in this review. Of the trials conducted in hospital settings, the majority had small sample sizes. There were 22 different interventions studied across the included trials and the most commonly studied antiseptics were 70% alcohol, triple dye and chlorhexidine.Only one antiseptic, chlorhexidine was studied in community settings for umbilical cord care. Three community trials reported data on all-cause mortality that comprised 1325 deaths in 54,624 participants and combined results showed a reduction of 23% (average risk ratio (RR) 0.77, 95% confidence interval (CI) 0.63 to 0.94, random-effects, T2 = 0.02, I2 = 50%) in the chlorhexidine group compared with control. The reduction in omphalitis ranged from 27% to 56% depending on the severity of infection. Cord separation time was increased by 1.7 days in the chlorhexidine group compared with dry cord care (mean difference (MD) 1.75 days, 95% CI 0.44 to 3.05, random-effects, T2 = 0.88, I2 = 100%). Washing of umbilical cord with soap and water was not advantageous compared with dry cord care in community settings.Among studies conducted in hospital settings, no study reported data for mortality or tetanus. No antiseptic was advantageous to reduce the incidence of omphalitis compared with dry cord care in hospital settings. Topical triple dye application reduced bacterial colonization with Staphylococcus aureus compared with dry cord care (average RR 0.15, 95% CI 0.10 to 0.22, four studies, n = 1319, random-effects, T2 = 0.04, I2 = 24%) or alcohol application (average RR 0.45, 95% CI 0.25 to 0.80, two studies, n = 487, random-effects, T2 = 0.00, I2 = 0%). There was no advantage of application of alcohol and triple dye for reduction of colonization with streptococcus. Topical alcohol application was advantageous in reduction of colonization with Enterococcus coli compared with dry cord care (average RR 0.73, 95% CI 0.58 to 0.92, two studies, n = 432, random-effects, T2 = 0.00, I2 = 0%) and in a separate analysis, triple dye increased the risk of colonization compared with alcohol (RR 3.44, 95% CI 2.10 to 5.64, one study, n = 373). Cord separation time was significantly increased with topical application of alcohol (MD 1.76 days, 95% CI 0.03 to 3.48, nine studies, n = 2921, random-effects, T2 = 6.54, I2 = 97%) and triple dye (MD 4.10 days, 95% CI 3.07 to 5.13, one study, n = 372) compared with dry cord care in hospital settings. The number of studies was insufficient to make any inference about the efficacy of other antiseptics. There is significant evidence to suggest that topical application of chlorhexidine to umbilical cord reduces neonatal mortality and omphalitis in community and primary care settings in developing countries. It may increase cord separation time however, there is no evidence that it increases risk of subsequent morbidity or infection.There is insufficient evidence to support the application of an antiseptic to umbilical cord in hospital settings compared with dry cord care in developed countries.

Hanes S.D.,SUNY Upstate Medical University
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2014

Ess1 is a prolyl isomerase that regulates the structure and function of eukaryotic RNA polymerase II. Ess1 works by catalyzing the cis/. trans conversion of pSer5-Pro6 bonds, and to a lesser extent pSer2-Pro3 bonds, within the carboxy-terminal domain (CTD) of Rpb1, the largest subunit of RNA pol II. Ess1 is conserved in organisms ranging from yeast to humans. In budding yeast, Ess1 is essential for growth and is required for efficient transcription initiation and termination, RNA processing, and suppression of cryptic transcription. In mammals, Ess1 (called Pin1) functions in a variety of pathways, including transcription, but it is not essential. Recent work has shown that Ess1 coordinates the binding and release of CTD-binding proteins that function as co-factors in the RNA pol II complex. In this way, Ess1 plays an integral role in writing (and reading) the so-called CTD code to promote production of mature RNA pol II transcripts including non-coding RNAs and mRNAs. © 2014 Elsevier B.V.

Kerr W.G.,SUNY Upstate Medical University
Annals of the New York Academy of Sciences | Year: 2011

SHIP1 is at the nexus of intracellular signaling pathways in immune cells that mediate bone marrow (BM) graft rejection, production of inflammatory and immunosuppressive cytokines, immunoregulatory cell formation, the BM niche that supports development of the immune system, and immune cancers. This review summarizes how SHIP participates in normal immune physiology or the pathologies that result when SHIP is mutated. This review also proposes that SHIP can have either inhibitory or activating roles in cell signaling that are determined by whether signaling pathways distal to PI3K are promoted by SHIP's substrate (PI(3,4,5)P 3) or its product (PI(3,4)P 2). This review also proposes the "two PIP hypothesis" that postulates that both SHIP's product and its substrate are necessary for a cancer cell to achieve and sustain a malignant state. Finally, due to the recent discovery of small molecule antagonists and agonists for SHIP, this review discusses potential therapeutic settings where chemical modulation of SHIP might be of benefit. © 2010 New York Academy of Sciences.

Agency: NSF | Branch: Standard Grant | Program: | Phase: CROSS-EF ACTIVITIES | Award Amount: 199.58K | Year: 2016

This RAPID award will enable researchers to determine the prevalence of the Zika virus and dengue virus co-infections in humans and mosquitos, household climatic factors affecting disease transmission, and which other species of mosquitos might transmit Zika. This project will fill in gaps to our knowledge about pathogen levels in the blood for a particular part of the human population, infection rates, co-infection between Zika and dengue in both humans and mosquitos, and what other mosquitos are able to transmit Zika. Building on an on-going study of mosquito-borne disease in Ecuador, the rapid deployment of this study will capture the spread of Zika through a naive population. The results will provide important information that can be used to control the spread of Zika in other locales, including the continental US. Results from this project will be relevant to the Zika public health emergency, and the researchers have set in place mechanisms to share quality-assured interim and final data as rapidly and widely as possible, including with public health and research communities.

This project will assess the spatiotemporal distribution of Zika and dengue virus infections in humans and mosquitoes in Ecuador by collecting household-level data for the following: i) blood draws for infection monitoring, febrile episodes, and household surveillance where mosquitos are positive for Zika virus, ii) climate data, and iii) biweekly mosquito collections and dengue virus diagnostics expanded for Zika virus. This data, combined with mosquito control interventions by the government and individual households, and information on socio-ecological conditions will be incorporated into modeling of local Zika transmission and mosquito dynamics. This will allow for a framework to assess drivers and mosquito control at scales from households to the entire region. This project will identify and compare drivers for Zika and dengue viruses to reveal key factors in the spread of Zika virus.

Agency: NSF | Branch: Continuing grant | Program: | Phase: Genetic Mechanisms | Award Amount: 440.00K | Year: 2015

The main goal of this project is to understand how non-coding RNA molecules help the embryos of animals establish an anterior end (or head) and a posterior end (or tail) during development. Recently, non-coding RNA molecules (called non-coding because they do not code for proteins) have been implicated in this developmental process. This project aims to discover how a non-coding RNA called 7SK helps control anterior development. The results will be important for the fundamental understanding of how animals develop, and may find future applications in nanotechnology. The project will involve the training of junior scientists at the post-doctoral, graduate and undergraduate levels.

Long non-coding RNAs have emerged as critical regulators of gene expression, but how they function is still a mystery. Here, an unusual non-coding RNA polymerase III transcript called 7SK RNA and its key regulator, the Bin3 RNA methyltransferase (called MePCE in mammals), will be studied. 7SK RNA is conserved from yeast to humans and plays critical roles in both transcription and translation. Bin3 seems to have co-evolved with 7SK RNA and methylates its 5-y-phosphate. Bin3 was discovered in Drosophila melanogaster where it is required for proper anterior-posterior embryo development. The mechanism is not known. The proposed experiments will: (1) test the model that methylation of 7SK RNA by Bin3 is important for Bicoid-dependent repression of caudal mRNA translation; (2) determine the step in translation at which the Bin3-7SK-RNA complex exerts it regulatory effect; (3) determine whether Bin3 targets other non-coding RNAs for 5-y-methylation and whether it represses translation of other mRNAs. The results will help in determining exactly how embryo development is controlled by non-coding RNAs in Drosophila and provide a model for how the Bin3-7SK-RNA complex works in other eukaryotic organisms. The integrated approach will combine genetics, biochemistry, bioinformatics and computational prediction.

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