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Search Results: 1 - 10 of 13 matches for " Lonny Lundsten "
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Spotlight 6: Davidson Seamount
David Clague,Lonny Lundsten,James Hein,Jennifer Paduan
Oceanography , 2010,
Abstract: Davidson Seamount is located about 80 km off the central California coast in the Monterey Bay National Marine Sanctuary. It is one of the better-explored seamounts in the world, having been sampled and observed during 32 dives by the remotely operated vehicle (ROV) Tiburon. These dives mapped the bottom substrate and biological communities, and collected over 280 rock samples and nearly as many benthic animals.
Endemicity, Biogeography, Composition, and Community Structure On a Northeast Pacific Seamount
Craig R. McClain, Lonny Lundsten, Micki Ream, James Barry, Andrew DeVogelaere
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004141
Abstract: The deep ocean greater than 1 km covers the majority of the earth's surface. Interspersed on the abyssal plains and continental slope are an estimated 14000 seamounts, topographic features extending 1000 m off the seafloor. A variety of hypotheses are posited that suggest the ecological, evolutionary, and oceanographic processes on seamounts differ from those governing the surrounding deep sea. The most prominent and oldest of these hypotheses, the seamount endemicity hypothesis (SMEH), states that seamounts possess a set of isolating mechanisms that produce highly endemic faunas. Here, we constructed a faunal inventory for Davidson Seamount, the first bathymetric feature to be characterized as a ‘seamount’, residing 120 km off the central California coast in approximately 3600 m of water (Fig 1). We find little support for the SMEH among megafauna of a Northeast Pacific seamount; instead, finding an assemblage of species that also occurs on adjacent continental margins. A large percentage of these species are also cosmopolitan with ranges extending over much of the Pacific Ocean Basin. Despite the similarity in composition between the seamount and non-seamount communities, we provide preliminary evidence that seamount communities may be structured differently and potentially serve as source of larvae for suboptimal, non-seamount habitats.
Physiological Sensing of Carbon Dioxide/Bicarbonate/pH via Cyclic Nucleotide Signaling
Jochen Buck,Lonny R. Levin
Sensors , 2011, DOI: 10.3390/s110202112
Abstract: Carbon dioxide (CO2) is produced by living organisms as a byproduct of metabolism. In physiological systems, CO2 is unequivocally linked with bicarbonate (HCO3?) and pH via a ubiquitous family of carbonic anhydrases, and numerous biological processes are dependent upon a mechanism for sensing the level of CO2, HCO3, and/or pH. The discovery that soluble adenylyl cyclase (sAC) is directly regulated by bicarbonate provided a link between CO2/HCO3/pH chemosensing and signaling via the widely used second messenger cyclic AMP. This review summarizes the evidence that bicarbonate-regulated sAC, and additional, subsequently identified bicarbonate-regulate nucleotidyl cyclases, function as evolutionarily conserved CO2/HCO3/pH chemosensors in a wide variety of physiological systems.
Identification of a haem domain in human soluble adenylate cyclase
Sabine Middelhaufe,Martina Leipelt,Lonny?R. Levin,Jochen Buck
Bioscience Reports , 2012, DOI: 10.1042/bsr20120051
Abstract: The second messengers cAMP and cGMP mediate a multitude of physiological processes. In mammals, these cyclic nucleotides are formed by related Class III nucleotidyl cyclases, and both ACs (adenylate cyclases) and GCs (guanylate cyclases) comprise transmembrane receptors as well as soluble isoforms. Whereas sGC (soluble GC) has a well-characterized regulatory HD (haem domain) that acts as a receptor for the activator NO (nitric oxide), very little is known about the regulatory domains of the ubiquitous signalling enzyme sAC (soluble AC). In the present study, we identify a unique type of HD as a regulatory domain in sAC. The sAC-HD (sAC haem domain) forms a larger oligomer and binds, non-covalently, one haem cofactor per monomer. Spectral analyses and mutagenesis reveal a 6-fold co-ordinated haem iron atom, probably with non-typical axial ligands, which can bind both NO and CO (carbon monoxide). Splice variants of sAC comprising this domain are expressed in testis and skeletal muscle, and the HD displays an activating effect on the sAC catalytic core. Our results reveal a novel mechanism for regulation of cAMP signalling and suggest a need for reanalysis of previous studies on mechanisms of haem ligand effects on cyclic nucleotide signalling, particularly in testis and skeletal muscle.
Evaluation of a task-shifting strategy involving peer educators in HIV care and treatment clinics in Lusaka, Zambia
Lonny J. Born,Chibesa Wamulume,Kim A. Neroda,Nicole Quiterio
Journal of Public Health in Africa , 2012, DOI: 10.4081/jphia.2012.e3
Abstract: Rapid expansion of antiretroviral therapy (ART) and a shortage of health care workers (HCWs) required the implementation of a peer educator (PE) model as part of a task-shifting strategy in Lusaka District clinics. The purpose of this study was to evaluate patient and staff perceptions regarding whether the PE program: a) relieved the workload on professional HCWs; and b) delivered services of acceptable quality. Qualitative and quantitative data were gathered from five primary care clinics delivering ART in Lusaka, Zambia. Closed surveys were conducted with 148 patients receiving ART, 29 PEs, and 53 HCWs. Data was imported into Microsoft Excel to calculate descriptive statistics. Six focus group discussions and eight key informant (KI) interviews were conducted, recorded, transcribed, and coded to extract relevant data. Survey results demonstrated that 50 of 53 (96.1%) HCWs agreed PEs reduced the amount of counseling duties required of HCWs. HCWs felt that PEs performed as well as HCWs in counseling patients (48 of 53; 90.6%) and that having PEs conduct counseling enabled clinical staff to see more patients (44 of 53; 83%). A majority of patients (141 of 148; 95.2%) agreed or strongly agreed that PEs were knowledgeable about ART, and 89 of 144 (61.8%) expressed a high level of confidence with PEs performing counseling and related tasks. Focus group and KI interviews supported these findings. PEs helped ease the work burden of HCWs and provided effective counseling, education talks, and adherence support to patients in HIV care. Consideration should be given to formalizing their role in the public health sector.
The Novel CFTR Mutation A457P in a Male with a Delayed Diagnosis of Cystic Fibrosis
Kate H. Cole,Patrick R. Sosnay,Lonny B. Yarmus,Jonathan B. Zuckerman
Case Reports in Medicine , 2011, DOI: 10.1155/2011/903910
Abstract: Cystic fibrosis (CF) is an autosomal recessive disease that may be caused by more than 1000 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We describe the case of a CF patient who was initially diagnosed at 16 years of age after presenting with mild respiratory compromise and pancreatic sufficiency. When genetic testing was first performed using a CF mutation panel, only a single F508del CFTR allele was identified. We subsequently performed testing, which revealed a previously unreported mutation: A457P (p.Ala457Pro, c.1369G>C). The patient's clinical course through adulthood is described, and genotype-phenotype correlation is discussed. The A457P mutation appears to confer a relatively mild phenotype, as is usually observed with CFTR class IV–VI defects. With the advent of more comprehensive and widely available genetic testing techniques, identification of CF genotypes in patients with milder disease variants may help stratify patients for targeted therapy and prevent late complications of the disease.
Somatic ‘Soluble’ Adenylyl Cyclase Isoforms Are Unaffected in Sacytm1Lex/Sacytm1Lex ‘Knockout’ Mice
Jeanne Farrell, Lavoisier Ramos, Martin Tresguerres, Margarita Kamenetsky, Lonny R. Levin, Jochen Buck
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003251
Abstract: Background Mammalian Soluble adenylyl cyclase (sAC, Adcy10, or Sacy) represents a source of the second messenger cAMP distinct from the widely studied, G protein-regulated transmembrane adenylyl cyclases. Genetic deletion of the second through fourth coding exons in Sacytm1Lex/Sacytm1Lex knockout mice results in a male sterile phenotype. The absence of any major somatic phenotype is inconsistent with the variety of somatic functions identified for sAC using pharmacological inhibitors and RNA interference. Principal Findings We now use immunological and molecular biological methods to demonstrate that somatic tissues express a previously unknown isoform of sAC, which utilizes a unique start site, and which ‘escapes’ the design of the Sacytm1Lex knockout allele. Conclusions/Significance These studies reveal increased complexity at the sAC locus, and they suggest that the known isoforms of sAC play a unique function in male germ cells.
Evidence and Value: Impact on DEcisionMaking – the EVIDEM framework and potential applications
Mireille M Goetghebeur, Monika Wagner, Hanane Khoury, Randy J Levitt, Lonny J Erickson, Donna Rindress
BMC Health Services Research , 2008, DOI: 10.1186/1472-6963-8-270
Abstract: Extensive analyses of the literature and of documented decisionmaking processes around the globe were performed to explore what steps are currently used to make decisions with respect to context (from evidence generation to communication of decision) and thought process (conceptual components of decisions). Needs and methodologies available to support decisionmaking were identified to lay the groundwork for the EVIDEM framework.A framework was developed consisting of seven modules that can evolve over the life cycle of a healthcare intervention. Components of decision that could be quantified, i.e., intrinsic value of a healthcare intervention and quality of evidence available, were organized into matrices. A multicriteria decision analysis (MCDA) Value Matrix (VM) was developed to include the 15 quantifiable components that are currently considered in decisionmaking. A methodology to synthesize the evidence needed for each component of the VM was developed including electronic access to full text source documents. A Quality Matrix was designed to quantify three criteria of quality for the 12 types of evidence usually required by decisionmakers. An integrated system was developed to optimize data analysis, synthesis and validation by experts, compatible with a collaborative structure.The EVIDEM framework promotes transparent and efficient healthcare decisionmaking through systematic assessment and dissemination of the evidence and values on which decisions are based. It provides a collaborative framework that could connect all stakeholders and serve the healthcare community at local, national and international levels by allowing sharing of data, resources and values. Validation and further development is needed to explore the full potential of this approach.The objective of any healthcare intervention is to improve health; preventive measures, non-pharmacological and pharmacological treatments, and medical procedures are among the numerous available options. Decisio
Activation of Soluble Adenylyl Cyclase Protects against Secretagogue Stimulated Zymogen Activation in Rat Pancreaic Acinar Cells
Thomas R. Kolodecik, Christine A. Shugrue, Edwin C. Thrower, Lonny R. Levin, Jochen Buck, Fred S. Gorelick
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0041320
Abstract: An early feature of acute pancreatitis is activation of zymogens, such as trypsinogen, within the pancreatic acinar cell. Supraphysiologic concentrations of the hormone cholecystokinin (CCK; 100 nM), or its orthologue cerulein (CER), induce zymogen activation and elevate levels of cAMP in pancreatic acinar cells. The two classes of adenylyl cyclase, trans-membrane (tmAC) and soluble (sAC), are activated by distinct mechanisms, localize to specific subcellular domains, and can produce locally high concentrations of cAMP. We hypothesized that sAC activity might selectively modulate acinar cell zymogen activation. sAC was identified in acinar cells by PCR and immunoblot. It localized to the apical region of the cell under resting conditions and redistributed intracellularly after treatment with supraphysiologic concentrations of cerulein. In cerulein-treated cells, pre-incubation with a trans-membrane adenylyl cyclase inhibitor did not affect zymogen activation or amylase secretion. However, treatment with a sAC inhibitor (KH7), or inhibition of a downstream target of cAMP, protein kinase A (PKA), significantly enhanced secretagogue-stimulated zymogen activation and amylase secretion. Activation of sAC with bicarbonate significantly inhibited secretagogue-stimulated zymogen activation; this response was decreased by inhibition of sAC or PKA. Bicarbonate also enhanced secretagogue-stimulated cAMP accumulation; this effect was inhibited by KH7. Bicarbonate treatment reduced secretagogue-stimulated acinar cell vacuolization, an early marker of pancreatitis. These data suggest that activation of sAC in the pancreatic acinar cell has a protective effect and reduces the pathologic activation of proteases during pancreatitis.
Characterization of Plasmodium falciparum Adenylyl Cyclase-β and Its Role in Erythrocytic Stage Parasites
Eric Salazar, Erin M. Bank, Nicole Ramsey, Kenneth C. Hess, Kirk W. Deitsch, Lonny R. Levin, Jochen Buck
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039769
Abstract: The most severe form of human malaria is caused by the parasite Plasmodium falciparum. The second messenger cAMP has been shown to be important for the parasite’s ability to infect the host’s liver, but its role during parasite growth inside erythrocytes, the stage responsible for symptomatic malaria, is less clear. The P. falciparum genome encodes two adenylyl cyclases, the enzymes that synthesize cAMP, PfACα and PfACβ. We now show that one of these, PfACβ, plays an important role during the erythrocytic stage of the P. falciparum life cycle. Biochemical characterization of PfACβ revealed a marked pH dependence, and sensitivity to a number of small molecule inhibitors. These inhibitors kill parasites growing inside red blood cells. One particular inhibitor is selective for PfACβ relative to its human ortholog, soluble adenylyl cyclase (sAC); thus, PfACβ represents a potential target for development of safe and effective antimalarial therapeutics.
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