Syracuse, NY, United States
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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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.

Faraone S.V.,SUNY Upstate Medical University
British Journal of Psychiatry | Year: 2013

Larsson et al provide epidemiological evidence for a genetic association between attention-deficit hyperactivity disorder (ADHD) and both bipolar disorder and schizophrenia and Hamshere and colleagues confirm the latter association with genome-wide data. Although a genetic link between ADHD and bipolar disorder has been hypothesised for over a decade, the association with schizophrenia fills a notable gap in the literature. This editorial discusses the implications of these findings for clinicians, who must address psychiatric comorbidity in their treatment formulations, and researchers who are learning that the discrete categorical diagnoses of our diagnostic systems may not be up to the task of clarifying the causes and cures of psychopathology.

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.

Agency: NSF | Branch: Standard Grant | Program: | Phase: Biomechanics & Mechanobiology | Award Amount: 198.96K | Year: 2013

The goal of this research project is to employ programmable materials from the field of biomaterials science, particle-tracking algorithms from the fields of biomechanics and biophysics, and molecular probes from the fields of cell and molecular biology to track and model the interaction of multiple intracellular components and the resultant large-scale cellular behaviors. A grand challenge in biomechanics and mechanobiology is that of understanding the complex interactions that occur between intracellular structures and how those interactions produce function at the cell and tissue levels. Through three objectives, this project will yield a method for quantitatively characterizing interactions between intracellular components and linking those patterns with large-scale behaviors such as cell polarization. First, the biomechanical sequence of cell polarization at the intracellular level will be elucidated via automated, synchronized tracking of multiple components in single cells in highly constrained environments. Second, cell polarization will be induced in individual cells using smart substrates and patterns in intracellular components will be linked to this large-scale cell behavior. Third, cell polarization will be studied and modeled, from the intracellular to multicellular levels, in a model of contact inhibition release/localized epithelial-mesenchymal transition with high cell densities. Coordinated cell movements are critical to biological processes such as embryonic development, cancer progression, and wound healing. Although cell movement is generated by structures inside cells, it is not known how interactions of those structures produce cell movement and resulting organization within groups of cells. This project will answer that question. A new computational approach will quantify the simultaneously interactions of several different important structures inside cells. New smart material will be used to trigger changes to cell movement, and the computational approach will determine how interactions of structures inside cells also change. Both low cell densities, where cells interact rarely, and high cell densities, where cells are always touching as happens in living organisms, will be studied. A model for collective movement of large groups of cells that can make predictions about tissues formation and disease will be developed.

Society will benefit from the technical and professional development of the individuals involved, important advances in the fields of biomechanics, biophysics, and biology, and breakthroughs that can be anticipated in healthcare fields. Research, education, and diversity at both collaborating institutions will be further integrated through a yearly summer research program that will recruit exceptional Hampton University students as undergraduate researchers.

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